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Abstract Microorganisms are present in snow/ice of the Antarctic Plateau, but their biogeography and metabolic state under extreme local conditions are poorly understood. Here, we show the diversity and distribution of microorganisms in air (1.5 m height) and snow/ice down to 4 m depth at three distant latitudes along a 2578 km transect on the East Antarctic Plateau on board an environmentally friendly, mobile platform. Results demonstrate the widespread distribution of microorganisms in the ice down to at least 4 m depth. Data point to geochemical and bacterial geographic distribution that correlate with wind trajectory and speed, modulated by local gathering and recirculation of microorganisms through snow drifting. Reservoir effects and community selection appear to occur over time, favoring microorganisms best adapted to hypothermal and hyperarid conditions. A new cyanobacterial species (Gloeocapsopsis sp) was isolated from 3 to 4 m depth. Our findings suggest that some microorganisms could exhibit transient, basal metabolic activity when associated to high salt particles, contributing to set biodiversity patterns and biogeographic compartmentalization on Antarctic Plateau ice.

A relação dos jesuítas com a ciência não é um tema novo, mas certamente desperta paixões e debates tão intensos quanto a evangelização e a educação inacianas. Os jesuítas e as Ciências no Brasil e Portugal: quando a história se (re)faz é um exemplo do que alguns classificam como Nova História ou Nova Historiografia da Companhia de Jesus. A coletânea foi publicada, em formato impresso e digital, em 2020, pela Cátedra Unesco de Juventude, Educação e Sociedade, da Universidade Católica de Brasília (UCB). O livro é organizado pelo doutor em Sociologia e professor do Programa de Pós-Graduação Stricto Sensu em Educação da UCB, Carlos Ângelo de Meneses Sousa, e pela doutora em Educação, Sheila Cristina Monteiro Matos...

Bisphenols are a group of organic compounds used frequently in industries to make plastics, coatings, and resins. These compounds recently gained attention due to their potential endocrine-disrupting effects. Bisphenol A (BPA) is the most studied compound among the bisphenol group. Many countries have banned the use of bisphenol A (BPA) because of its toxic effects, which have led to the invention of other bisphenol analogs, such as bisphenol F, bisphenol B, bisphenol P, and bisphenol AF. Many studies found that bisphenol analogs may also pose endocrine-disrupting effects like BPA or can be even more toxic. Additionally, they may exhibit genotoxicity, cytotoxicity, and reproductive toxicity. Increased concentrations of bisphenol analogs have been detected in the abiotic environment and human urine. In some regions, the detected quantity is similar to or higher than BPA. However, a significant research gap exists concerning the precise elucidation of the mechanism of action, adverse physiological effects, and ramifications for human health associated with bisphenol analogs. Consequently, a compelling need arises for more research and the accumulation of empirical data to address the consequences of bisphenol analog exposure and ensure public health preservation. The findings resulting from initiatives in biomonitoring and varied explorations into the detrimental effects of bisphenol analogs accentuate the pressing requirement for a more exhaustive investigation. This manuscript provides a comprehensive review of the prevalence and toxicity of bisphenol analogs, along with existing knowledge gaps. It underscores the need to address these gaps for effective regulatory and public health strategies, contributing to a more informed approach to managing the potential risks posed by these analogs.

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17–44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.

Large Conductance Voltage- and Calcium-activated K+ (BK) channels are transmembrane pore-forming proteins that regulate cell excitability and are also expressed in non-excitable cells. They play a role in regulating vascular tone, neuronal excitability, neurotransmitter release, and muscle contraction. Dysfunction of the BK channel can lead to arterial hypertension, hearing disorders, epilepsy, and ataxia. Here, we provide an overview of BK channel functioning and the implications of its abnormal functioning in various diseases. Understanding the function of BK channels is crucial for comprehending the mechanisms involved in regulating vital physiological processes, both in normal and pathological conditions, controlled by BK. This understanding may lead to the development of therapeutic interventions to address BK channelopathies.

With the recent advance in molecular phylogenetics focused on the leaf insects (Phasmatodea, Phylliidae), gaps in knowledge are beginning to be filled. Yet, shortcomings are also being highlighted, for instance, the unveiling of numerous undescribed phylliid species. Here, some of these taxa are described, including Phyllium iyadaon sp. nov. from Mindoro Island, Philippines; Phyllium samarense sp. nov. from Samar Island, Philippines; Phyllium ortizi sp. nov. from Mindanao Island, Philippines; Pulchriphyllium heracles sp. nov. from Vietnam; Pulchriphyllium delislei sp. nov. from South Kalimantan, Indonesia; and Pulchriphyllium bhaskarai sp. nov. from Java, Indonesia. Several additional specimens of these species together with a seventh species described herein, Pulchriphyllium anangu sp. nov. from southwestern India, were incorporated into a newly constructed phylogenetic tree. Additionally, two taxa that were originally described as species, but in recent decades have been treated as subspecies, are elevated back to species status to reflect their unique morphology and geographic isolation, creating the following new combinations: Pulchriphyllium scythe (Gray, 1843) stat. rev., comb. nov. from Bangladesh and northeastern India, and Pulchriphyllium crurifolium (Audinet-Serville, 1838) stat. rev., comb. nov. from the Seychelles islands. Lectotype specimens are also designated for Pulchriphyllium scythe (Gray, 1843) stat. rev., comb. nov. and Pulchriphyllium crurifolium (Audinet-Serville, 1838) stat. rev., comb. nov. from original type material.

Abstract Background Metabolic dysfunction and cachexia are associated with poor cancer prognosis. With no pharmacological treatments, it is crucial to define the molecular mechanisms causing cancer‐induced metabolic dysfunction and cachexia. Adenosine monophosphate‐activated protein kinase (AMPK) connects metabolic and muscle mass regulation. As AMPK could be a potential treatment target, it is important to determine the function for AMPK in cancer‐associated metabolic dysfunction and cachexia. We therefore established AMPK's roles in cancer‐associated metabolic dysfunction, insulin resistance and cachexia. Methods In vastus lateralis muscle biopsies from n = 26 patients with non‐small cell lung cancer (NSCLC), AMPK signalling and protein content were examined by immunoblotting. To determine the role of muscle AMPK, male mice overexpressing a dominant‐negative AMPKα2 (kinase‐dead [KiDe]) specifically in striated muscle were inoculated with Lewis lung carcinoma (LLC) cells (wild type [WT]: n = 27, WT + LLC: n = 34, mAMPK‐KiDe: n = 23, mAMPK‐KiDe + LLC: n = 38). Moreover, male LLC‐tumour‐bearing mice were treated with (n = 10)/without (n = 9) 5‐aminoimidazole‐4‐carboxamide ribonucleotide (AICAR) to activate AMPK for 13 days. Littermate mice were used as controls. Metabolic phenotyping of mice was performed via indirect calorimetry, body composition analyses, glucose and insulin tolerance tests, tissue‐specific 2‐[3H]deoxy‐d‐glucose (2‐DG) uptake and immunoblotting. Results Patients with NSCLC presented increased muscle protein content of AMPK subunits α1, α2, β2, γ1 and γ3 ranging from +27% to +79% compared with control subjects. In patients with NSCLC, AMPK subunit protein content correlated with weight loss (α1, α2, β2 and γ1), fat‐free mass (α1, β2 and γ1) and fat mass (α1 and γ1). Tumour‐bearing mAMPK‐KiDe mice presented increased fat loss and glucose and insulin intolerance. LLC in mAMPK‐KiDe mice displayed lower insulin‐stimulated 2‐DG uptake in skeletal muscle (quadriceps: −35%, soleus: −49%, extensor digitorum longus: −48%) and the heart (−29%) than that in non‐tumour‐bearing mice. In skeletal muscle, mAMPK‐KiDe abrogated the tumour‐induced increase in insulin‐stimulated TBC1D4thr642 phosphorylation. The protein content of TBC1D4 (+26%), pyruvate dehydrogenase (PDH; +94%), PDH kinases (+45% to +100%) and glycogen synthase (+48%) was increased in skeletal muscle of tumour‐bearing mice in an AMPK‐dependent manner. Lastly, chronic AICAR treatment elevated hexokinase II protein content and normalized phosphorylation of p70S6Kthr389 (mTORC1 substrate) and ACCser212 (AMPK substrate) and rescued cancer‐induced insulin intolerance. Conclusions Protein contents of AMPK subunits were upregulated in skeletal muscle of patients with NSCLC. AMPK activation seemed protectively inferred by AMPK‐deficient mice developing metabolic dysfunction in response to cancer, including AMPK‐dependent regulation of multiple proteins crucial for glucose metabolism. These observations highlight the potential for targeting AMPK to counter cancer‐associated metabolic dysfunction and possibly cachexia.

Bioelectronic Medicine stands as an emerging field that rapidly evolves and offers distinctive clinical benefits, alongside unique challenges. It consists of the modulation of the nervous system by precise delivery of electrical current for the treatment of clinical conditions, such as post-stroke movement recovery or drug-resistant disorders. The unquestionable clinical impact of Bioelectronic Medicine is underscored by the successful translation to humans in the last decades, and the long list of preclinical studies. Given the emergency of accelerating the progress in new neuromodulation treatments (i.e., drug-resistant hypertension, autoimmune and degenerative diseases), collaboration between multiple fields is imperative. This work intends to foster multidisciplinary work and bring together different fields to provide the fundamental basis underlying Bioelectronic Medicine. In this review we will go from the biophysics of the cell membrane, which we consider the inner core of neuromodulation, to patient care. We will discuss the recently discovered mechanism of neurotransmission switching and how it will impact neuromodulation design, and we will provide an update on neuronal and glial basis in health and disease. The advances in biomedical technology have facilitated the collection of large amounts of data, thereby introducing new challenges in data analysis. We will discuss the current approaches and challenges in high throughput data analysis, encompassing big data, networks, artificial intelligence, and internet of things. Emphasis will be placed on understanding the electrochemical properties of neural interfaces, along with the integration of biocompatible and reliable materials and compliance with biomedical regulations for translational applications. Preclinical validation is foundational to the translational process, and we will discuss the critical aspects of such animal studies. Finally, we will focus on the patient point-of-care and challenges in neuromodulation as the ultimate goal of bioelectronic medicine. This review is a call to scientists from different fields to work together with a common endeavor: accelerate the decoding and modulation of the nervous system in a new era of therapeutic possibilities.

Objectives. We determined the clinical characteristics and prevalence of metabolic syndrome among adult Filipinos with overt hypothyroidism. Methodology. This is a cross-sectional study of 151 adults. Patients were recruited by sequential enrollment. Anthropometric and blood pressure measurements were performed followed by blood extraction for metabolic parameters and thyroid function tests. Clinical and laboratory characteristics were compared between patients with and without metabolic syndrome. Results. The prevalence of metabolic syndrome is 40.4% (95%CI: 32.5%, 48.7%). Patients with metabolic syndrome have a waist circumference of 88.4 ± 7.7 cm in females and 93.3 ± 9.0 cm in males. The median fasting blood glucose was 111.4 (52.2) mg/dL, median systolic blood pressure of 120 (30) mm Hg and diastolic blood pressure of 80 (20) mmHg, median serum triglycerides of 174.3 (114.2) mg/dL, median HDL-C of 42.3 (19.2) mg/dL and a proportion of patients with diabetes (23.0%) and hypertension (44.3%), respectively. The presence of increased waist circumference is the most prevalent component seen among hypothyroid patients. There were no differences in terms of age, sex, etiology of hypothyroidism and anti-TPO levels in those with and without metabolic syndrome. Conclusion. The prevalence of metabolic syndrome in adult Filipinos with hypothyroidism is high. Emphasis must be placed on early screening using waist circumference and metabolic parameters among hypothyroid patients who are at high risk of developing metabolic syndrome.

Over the past two decades, research has increasingly focused on the interactions between diet, gut microbiota, and host organisms. Recent evidence suggests that tryptophan, an essential amino acid, can be metabolized by gut microbiota into indoles, which have significant biological effects. However, most research is limited to indole and its liver metabolite, indoxyl sulfate. This study examines the cytotoxic effects of five indole derivatives — indole-3-carboxylic acid (I3CA), indole-3-aldehyde (I3A), indole-3-acetic acid (IAA), indole-3-propionic acid (IPA), and 3-methylindole (skatole, 3-MI) — on six human cell lines: adipose-derived mesenchymal stem cells (MSC), hepatocellular carcinoma (HepG2), liver progenitor cells (HepaRG), colorectal carcinoma cells (Caco-2), breast cancer cells (T47D), and lung fibroblast (MRC-5). Results show no sensitivity to indole itself across cell lines. MRC-5 was sensitive to all other compounds (EC50 0.52–49.8 µM). MSCs responded to IPA, I3CA, I3A, and 3-MI (EC50 0.33–1.87 µM), while HepaRG cells were affected by IAA, I3CA, I3A, and 3-MI (EC50 1.98–66.4 µM). T47D cells were sensitive to IPA and IAA, and Caco-2 cells only to IAA (EC50 2.02, 1.68, 0.52 µM, respectively). HepG2 cells showed no change in viability. AhR activation in HepG2-AhR-Lucia cells was triggered by all derivatives, particularly I3A, IPA, and I3CA. Growth experiments revealed I3CA decreased Caco-2 proliferation while increasing T47D proliferation. The findings suggest indole derivatives are generally non-cytotoxic to carcinomas but may adversely affect stem cells, with effects varying across cell lines.

Abstract Heterozygous mutations in the GRN gene and hexanucleotide repeat expansions in C9orf72 are the two most common genetic causes of Frontotemporal Dementia (FTD) with TDP-43 protein inclusions. The triggers for neurodegeneration in FTD with GRN (FTD-GRN) or C9orf72 (FTD-C9orf72) gene abnormalities are unknown, although evidence from mouse and cell culture models suggests that GRN mutations disrupt lysosomal lipid catabolism. To determine how brain lipid metabolism is affected in familial FTD with TDP-43 inclusions, and how this is related to myelin and lysosomal markers, we undertook comprehensive lipidomic analysis, enzyme activity assays, and western blotting on grey and white matter samples from the heavily-affected frontal lobe and less-affected parietal lobe of FTD-GRN cases, FTD-C9orf72 cases, and age-matched neurologically-normal controls. Substantial loss of myelin-enriched sphingolipids (sulfatide, galactosylceramide, sphingomyelin) and myelin proteins was observed in frontal white matter of FTD-GRN cases. A less-pronounced, yet statistically significant, loss of sphingolipids was also observed in FTD-C9orf72. FTD-GRN was distinguished from FTD-C9orf72 and control cases by increased acylcarnitines in frontal grey matter and marked accumulation of cholesterol esters in both frontal and parietal white matter, indicative of myelin break-down. Both FTD-GRN and FTD-C9orf72 cases showed significantly increased lysosomal and phagocytic protein markers, however galactocerebrosidase activity, required for lysosomal catabolism of galactosylceramide and sulfatide, was selectively increased in FTD-GRN. We conclude that both C9orf72 and GRN mutations are associated with disrupted lysosomal homeostasis and white matter lipid loss, but GRN mutations cause a more pronounced disruption to myelin lipid metabolism. Our findings support the hypothesis that hyperactive myelin lipid catabolism is a driver of gliosis and neurodegeneration in FTD-GRN. Since FTD-GRN is associated with white matter hyperintensities by MRI, our data provides important biochemical evidence supporting the use of MRI measures of white matter integrity in the diagnosis and management of FTD.

Objetivos: Este estudio tiene como objetivo analizar el comportamiento mensual de los precios mayoristas del queso costeño en siete grandes ciudades colombianas: Barranquilla, Bogotá, Bucaramanga, Cartagena, Cali, Cúcuta y Medellín. Se centra en comprender las fluctuaciones de los precios durante un periodo específico para identificar tendencias e implicaciones para el sector. Métodos: Los datos del Sistema de Información de Precios y Oferta Agropecuaria (SIPSA) cubrieron los precios mensuales al por mayor del queso costeño desde enero de 2015 hasta septiembre de 2022. Utilizando la metodología Box-Jenkins, el estudio realizó análisis de series temporales para estimar modelos econométricos para cada ciudad. Para el análisis estadístico se utilizó el programa Statgraphics 19-X-64. Resultados: Los modelos econométricos pronosticaron con precisión los precios del queso de costa para los tres últimos meses de 2022 y los tres primeros meses de 2023, mostrando sistemáticamente una tendencia al alza de los precios. Conclusión: El análisis de los precios mayoristas en las principales ciudades de Colombia demuestra una tendencia general al alza en los precios del queso costeño. Esta tendencia sugiere un escenario favorable para la comercialización del producto, indicando condiciones propicias para la expansión del mercado a nivel nacional.

Introducción: Este estudio tiene como objetivo analizar la enseñanza y el aprendizaje a distancia de la geografía en la educación media general venezolana durante la pandemia de covid-19 a partir de la percepción de los estudiantes de la Unidad Educativa Privada San Antonio de Padua. Metodología: La metodología empleada se fundamenta en el enfoque cuantitativo, que es una investigación descriptiva con un diseño no experimental y de campo. Para la recolección de información, se utilizó un cuestionario tipo Likert basado en las áreas de atención para la educación a distancia propuestas por Cubillán y Labarca-Rincón, que fue aplicado a los estudiantes de 4to y 5to año de la institución objeto de estudio. Resultados y Discusión: Entre los resultados destaca que más del 45 % de los estudiantes aseguran que las clases a distancia de geografía se basaron en el envío de actividades a realizar; el 65,6 % que las herramientas tecnológicas más usadas fueron WhatsApp y Telegram, y el 53,1 % que el profesor no utilizó herramientas propias de la geografía como Google Maps para desarrollar contenidos. Conclusiones: Se concluye que en el área pedagógica los docentes de Geografía se dedicaron a hacer un calco de la educación presencial a través de la virtualidad; en el área tecnológica, acudieron a herramientas digitales no específicas del área; en el área de diseño educativo, los docentes no diseñaron actividades propias de la geografía mediante tecnología adecuada, y en el área de investigación, no fue utilizada la tecnología para crear contenido sino para memorizar conceptos.

Abstract As a global health emergency, the rapid spread of the novel coronavirus disease (COVID-19) led to the implementation of widespread restrictions (e.g., quarantine, physical/social distancing measures). However, while these restrictions reduce the viral spread of COVID-19, they may exacerbate behavioural and cognitive symptoms in dementia patients and increase pressure on caregiving. Here, we aimed to assess the impact of COVID-19 and related restrictions on both carers and people living with dementia across the world. We conducted an international survey (Australia, Germany, Spain, and the Netherlands) to assess the impact of COVID-19 on carers and people living with dementia. People with dementia experienced worsened neuropsychiatric symptoms since the outbreak of COVID-19, most commonly, depression, apathy, delusions, anxiety, irritability, and agitation. Regression analyses revealed that limited understanding of the COVID-19 situation and not living with the carer was associated with worsened neuropsychiatric symptoms. Carers also reported a decline in their own mental health, increased stress and reduced social networks as a result of COVID-19 and related restrictions. Regression analyses revealed uncertainty about the future and loneliness were associated with worsened carer mental health. Findings from this study will inform strategies for the development of support services and compassionate protocols that meet the evolving needs of those living with dementia and their carers.

A growing public health concern, chronic Diesel Exhaust Particle (DEP) exposure is a heavy risk factor for the development of neurodegenerative diseases like Alzheimer’s (AD). Considered the brain’s first line of defense, the Blood–Brain Barrier (BBB) and perivascular microglia work in tandem to protect the brain from circulating neurotoxic molecules like DEP. Importantly, there is a strong association between AD and BBB dysfunction, particularly in the Aβ transporter and multidrug resistant pump, P-glycoprotein (P-gp). However, the response of this efflux transporter is not well understood in the context of environmental exposures, such as to DEP. Moreover, microglia are seldom included in in vitro BBB models, despite their significance in neurovascular health and disease. Therefore, the goal of this study was to evaluate the effect of acute (24 hr.) DEP exposure (2000 μg/ml) on P-gp expression and function, paracellular permeability, and inflammation profiles of the human in vitro BBB model (hCMEC/D3) with and without microglia (hMC3). Our results suggested that DEP exposure can decrease both the expression and function of P-gp in the BBB, and corroborated that DEP exposure impairs BBB integrity (i.e. increased permeability), a response that was significantly worsened by the influence of microglia in co-culture. Interestingly, DEP exposure seemed to produce atypical inflammation profiles and an unexpected general downregulation in inflammatory markers in both the monoculture and co-culture, which differentially expressed IL-1β and GM-CSF. Interestingly, the microglia in co-culture did not appear to influence the response of the BBB, save in the permeability assay, where it worsened the BBB’s response. Overall, our study is important because it is the first (to our knowledge) to investigate the effect of acute DEP exposure on P-gp in the in vitro human BBB, while also investigating the influence of microglia on the BBB’s responses to this environmental chemical.

Introduction There is a discrepancy in the literature as to whether authorising or refusing the recovery of organs for transplantation is of direct benefit to families in their subsequent grieving process. This study aims to explore the impact of the family interview to pose the option of posthumous donation and the decision to authorise or refuse organ recovery on the grieving process of potential donors’ relatives.Methods and analysis A protocol for mixed methods, prospective cohort longitudinal study is proposed. Researchers do not randomly assign participants to groups. Instead, participants are considered to belong to one of three groups based on factors related to their experiences at the hospital. In this regard, families in G1, G2 and G3 would be those who authorised organ donation, declined organ donation or were not asked about organ donation, respectively. Their grieving process is monitored at three points in time: 1 month after the patient’s death, when a semistructured interview focused on the lived experience during the donation process is carried out, 3 months and 9 months after the death. At the second and third time points, relatives’ grieving process is assessed using six psychometric tests: State-Trait Anxiety Inventory, Beck Depression Inventory-II, Inventory of Complicated Grief, The Impact of Event Scale: Revised, Posttraumatic Growth Inventory and Connor-Davidson Resilience Scale. Descriptive statistics (means, SDs and frequencies) are computed for each group and time point. Through a series of regression models, differences between groups in the evolution of bereavement are estimated. Additionally, qualitative analyses of the semistructured interviews are conducted using the ATLAS.ti software.Ethics and dissemination This study involves human participants and was approved by Comité Coordinador de Ética de la Investigación Biomédica de Andalucía (CCEIBA) ID:1052-N-21. The results will be disseminated at congresses and ordinary academic forums. Participants gave informed consent to participate in the study before taking part.

Short-chain per- and polyfluoroalkyl substances (PFAS) have been developed as alternatives to legacy long-chain PFAS, but they may still pose risks due to their potential to interact with biomolecules. Cytochrome P450 (CYP450) enzymes are essential for xenobiotic metabolism, and disruptions of these enzymes by PFAS can have significant human health implications. The inhibitory potential of two legacy long-chain (PFOA and PFOS) and five short-chain alternative PFAS (PFBS, PFHxA, HFPO-DA, PFHxS, and 6:2 FTOH) were assessed in recombinant CYP1A2, − 2B6, −2C19, −2E1, and −3A4 enzymes. Most of the short-chain PFAS, except for PFHxS, tested did not result in significant inhibition up to 100 μM. PFOS inhibited recombinant CYP1A2, −2B6, −2C19, and −3A4 enzymes. However, concentrations where inhibition occurred, were all higher than the averages reported in population biomonitoring studies, with IC50 values higher than 10 µM. We also evaluated the activities of CYP1A2 and CYP3A4 in HepaRG monolayers following 48 h exposures of the short-chain PFAS at two concentrations (1 nM or 1 µM) and with or without an inducer (benzo[a]pyrene, BaP, for CYP1A2 and rifampicin for CYP3A4). Our findings suggest that both 1 nM and 1 µM exposures to short-chain PFAS can modulate the CYP1A2 activity induced by BaP. Except for PFHxS, the short-chain PFAS appear to have little effect on CYP3A4 activity. Understanding the effects of PFAS exposure on biotransformation can shed light on the mechanisms of PFAS toxicity and aid in developing effective strategies for managing chemical risks, enabling regulators to make more informed decisions.

Objectives. Daily levothyroxine is the treatment of choice and standard of care in hypothyroidism, sufficient to restore thyroid stimulating hormone (TSH) to normal range. For many patients, daily lifelong therapy is required, making adherence a major issue. In such cases, weekly replacement may be a suitable alternative to improve adherence. In this study, we aimed to determine the efficacy and safety of weekly levothyroxine replacement among adults with hypothyroidism. Methodology. Electronic databases were searched. Two reviewers (HCC and RBL) independently screened the abstracts, reviewed full-text papers, critically appraised the quality of included studies using PRISMA guidelines. Meta-analysis was performed using the random-effects model. The primary outcome is the difference in serum TSH levels between weekly and daily administration, while secondary outcomes included adverse events and symptoms of hypothyroidism. Results. The primary outcome is the difference in serum TSH levels between weekly and daily administration. Secondary outcomes included adverse events and clinical symptoms. The study included two randomized trials (n=109) in the primary analysis. The difference in TSH levels was 1.78 mIU/mL higher [(95% confidence interval (CI): 1.28 to 2.28, p

We present an optimized dissociation protocol for preparing high-quality skin cell suspensions for in-depth single-cell RNA-sequencing (scRNA-seq) analysis of fresh and cultured human skin. Our protocol enabled the isolation of a consistently high number of highly viable skin cells from small freshly dissociated punch skin biopsies, which we use for scRNA-seq studies. We recapitulated not only the main cell populations of existing single-cell skin atlases, but also identified rare cell populations, such as mast cells. Furthermore, we effectively isolated highly viable single cells from ex vivo cultured skin biopsy fragments and generated a global single-cell map of the explanted human skin. The quality metrics of the generated scRNA-seq datasets were comparable between freshly dissociated and cultured skin. Overall, by enabling efficient cell isolation and comprehensive cell mapping, our skin dissociation-scRNA-seq workflow can greatly facilitate scRNA-seq discoveries across diverse human skin pathologies and ex vivo skin explant experimentations.

Bisphosphonates (BPs) are the most used bone-specific anti-resorptive agents, often chosen as first-line therapy in several bone diseases characterized by an imbalance between osteoblast-mediated bone production and osteoclast-mediated bone resorption. BPs target the farnesyl pyrophosphate synthase (FPPS) in osteoclasts, reducing bone resorption. Lately, there has been an increasing interest in BPs direct pro-survival/pro-mineralizing properties in osteoblasts and their pain-relieving effects. Even so, molecular targets involved in these effects appear now largely elusive. Ion channels are emerging players in bone homeostasis. Nevertheless, the effects of BPs on these proteins have been poorly described. Here we reviewed the actions of BPs on ion channels in musculoskeletal cells. In particular, the TRPV1 channel is essential for osteoblastogenesis. Since it is involved in bone pain sensation, TRPV1 is a possible alternative target of BPs. Ion channels are emerging targets and anti-target for bisphosphonates. Zoledronic acid can be the first selective musculoskeletal and vascular KATP channel blocker targeting with high affinity the inward rectifier channels Kir6.1-SUR2B and Kir6.2-SUR2A. The action of this drug against the overactive mutants of KCNJ9-ABCC9 genes observed in the Cantu’ Syndrome (CS) may improve the appropriate prescription in those CS patients affected by musculoskeletal disorders such as bone fracture and bone frailty.

La enseñanza de las Ciencias de la Tierra debe velar por el conocimiento que los estudiantes deben poseer referente a la geografía de su entorno inmediato. La investigación tiene como objetivo proponer un itinerario virtual basado en los afloramientos de la Formación El Milagro para la enseñanza de procesos geológicos en el área de formación Ciencias de la Tierra. La línea metodológica es descriptiva y proyectiva, con un diseño de campo. Los instrumentos utilizados fueron un cuestionario de preguntas cerradas y una prueba estandarizada de conocimientos, validados por cuatro (4) expertos. En la indagación de los recursos didácticos de orden tecnológico utilizados por los docentes, se obtuvo que en el indicador “páginas web” un 50% asegura nunca utilizarlas en la enseñanza de las Ciencias de la Tierra; destaca que el 100% asegura nunca diseñar itinerarios geológicos virtuales. En referencia al nivel de conocimiento sobre procesos geológicos que poseen los estudiantes, sólo un promedio del 30% respondió acertadamente en los ítems que agrupan los indicadores “vegetación, “litología”, “erosión”, “procesos estratigráficos” y “procesos de ladera” de la Formación el Milagro, lo cual denota debilidad en el domino del conocimiento. Para dar solvencia al diagnóstico señalado, se propone un itinerario geológico virtual basado en los afloramientos de la Formación El Milagro del estado Zulia (Venezuela) para dinamizar la enseñanza de procesos geológicos en Educación Media General. Su aplicación logra favorecer la dinámica educativa en el área de formación Ciencias de la Tierra.

Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance via inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy via effects on muscle protein turnover. To investigate this, eight-week-old male C57BL/6J mice were fed a chow (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce hepatic steatosis, after which the livers were excised and cut into ~200-µm slices. Slices were cultured to collect secretion products (conditioned medium; CM). Differentiated L6-GLUT4myc myotubes were incubated with chow or HFD CM to measure glucose uptake. Differentiated C2C12 myotubes were incubated with chow or HFD CM to measure protein synthesis and breakdown, and gene expression via RNA sequencing. Furthermore, proteomics analysis was performed in chow and HFD CM. It was found that HFD CM caused insulin resistance in L6-GLUT4myc myotubes compared with chow CM, as indicated by a blunted insulin-stimulated increase in glucose uptake. Furthermore, protein breakdown was increased in C2C12 cells incubated with HFD CM, while there was no effect on protein synthesis. RNA profiling of C2C12 cells indicated that 197 genes were differentially expressed after incubation with HFD CM, compared with chow CM, and pathway analysis showed that pathways related to anatomical structure and function were enriched. Proteomics analysis of the CM showed that 32 proteins were differentially expressed in HFD CM compared with chow CM. Pathway enrichment analysis indicated that these proteins had important functions with respect to insulin-like growth factor transport and uptake, and affect post-translational processes, including protein folding, protein secretion and protein phosphorylation. In conclusion, the results of this study support the hypothesis that secretion products from the liver contribute to the development of muscle atrophy in individuals with hepatic steatosis.

In the 1970s, calcium-activated potassium currents were recorded for the first time. In 10years, this Ca2+-activated potassium channel was identified in rat skeletal muscle, chromaffin cells and characterized in skeletal muscle membranes reconstituted in lipid bilayers. This calcium- and voltage-activated potassium channel, dubbed BK for “Big K” due to its large ionic conductance between 130 and 300 pS in symmetric K+. The BK channel is a tetramer where the pore-forming α subunit contains seven transmembrane segments. It has a modular architecture containing a pore domain with a highly potassium-selective filter, a voltage-sensor domain and two intracellular Ca2+ binding sites in the C-terminus. BK is found in the plasma membrane of different cell types, the inner mitochondrial membrane (mitoBK) and the nuclear envelope’s outer membrane (nBK). Like BK channels in the plasma membrane (pmBK), the open probability of mitoBK and nBK channels are regulated by Ca2+ and voltage and modulated by auxiliary subunits. BK channels share common pharmacology to toxins such as iberiotoxin, charybdotoxin, paxilline, and agonists of the benzimidazole family. However, the precise role of mitoBK and nBK remains largely unknown. To date, mitoBK has been reported to play a role in protecting the heart from ischemic injury. At the same time, pharmacology suggests that nBK has a role in regulating nuclear Ca2+, membrane potential and expression of eNOS. Here, we will discuss at the biophysical level the properties and differences of mitoBK and nBK compared to those of pmBK and their pharmacology and function.

Abstract Introduction Timely diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging because it depends on clinical expertise and potentially ambiguous diagnostic guidelines. Recent recommendations highlight the role of multimodal neuroimaging and machine learning methods as complementary tools to address this problem. Methods We developed an automatic, cross‐center, multimodal computational approach for robust classification of patients with bvFTD and healthy controls. We analyzed structural magnetic resonance imaging and resting‐state functional connectivity from 44 patients with bvFTD and 60 healthy controls (across three imaging centers with different acquisition protocols) using a fully automated processing pipeline, including site normalization, native space feature extraction, and a random forest classifier. Results Our method successfully combined multimodal imaging information with high accuracy (91%), sensitivity (83.7%), and specificity (96.6%). Discussion This multimodal approach enhanced the system's performance and provided a clinically informative method for neuroimaging analysis. This underscores the relevance of combining multimodal imaging and machine learning as a gold standard for dementia diagnosis.

Abstract Background Frontotemporal dementia (FTD) is associated with complex changes in eating behavior and metabolism, which potentially affect disease pathogenesis and survival. It is currently not known if body composition changes and changes in fat deposition also exist in FTD, the relationship of these changes in eating behavior and appetite, and whether these changes are centrally mediated. Methods Body composition was measured in 28 people with behavioral‐variant frontotemporal dementia (bvFTD), 16 with Alzheimer’s disease (AD), and 19 healthy controls, using dual energy x‐ray absorptiometry. Changes in body composition were correlated to brain grey matter atrophy using voxel‐based morphometry on high‐resolution magnetic resonance imaging. Results Behavioral‐variant FTD was characterized by changes in body composition, with increased total fat mass, visceral adipose tissue area (VAT area), and android: gynoid ratio compared to control and AD participants (all P values

BK channels are composed by the pore forming α subunit and, in some tissues, is associated with different accessory β subunits. These proteins modify the biophysical properties of the channel, amplifying the range of BK channel activation according to the physiological context. In the vascular cells, the pore forming BKα subunit is expressed with the β1 subunit, where they play an essential role in the modulation of arterial tone and blood pressure. In eukaryotes, cholesterol is a structural lipid of the cellular membrane. Changes in the ratio of cholesterol content in the plasma membrane (PM) regulates the BK channel activation altering its open probability, and hence, vascular contraction. It has been shown that the estrogen 17β-Estradiol (E2) causes a vasodilator effect in vascular cells, inducing a leftward shift in the V0.5 of the GV curve. Here, we evaluate whether changes in the membrane cholesterol concentration modify the effect that E2 induces on the BKα/β1 channel activity. Using binding and electrophysiology assays after cholesterol depletion or enrichment, we show that the cholesterol enrichment significantly decreases the expression of the α subunit, while cholesterol depletion increased the expression of that α subunit. Additionally, we demonstrated that changes in the membrane cholesterol cause the loss of the modulatory effect of E2 on the BKα/β1 channel activity, without affecting the E2 binding to the complex. Our data suggest that changes in membrane cholesterol content could affect channel properties related to the E2 effect on BKα/β1 channel activity. Finally, the results suggest that an optimal membrane cholesterol content is essential for the activation of BK channels through the β1 subunit.

*Visual Abstracts prepared by Dr. Monica Therese Cating-Cabral Objectives. Effective communication has been correlated with improved outcomes in diabetes mellitus. Patient comprehension bears an effect on understanding, improving healthcare access and utilization, interaction with healthcare providers, caring for one’s own health, and shared decision making. Currently, there is a gamut of information on diabetes-related terms from various sources. However, no material has yet been available for clinical use in the third world setting. Hence, we explored the most common themes discussed during an outpatient diabetes consult in our hospital. Methodology. Consultation audio recordings (N = 96) and focus group discussions (N = 32) were conducted among adults with diabetes. Transcribed results underwent qualitative content and thematic analyses to develop the conceptual framework. Results. The study generated the following themes: diabetes mellitus diagnosis, lifestyle modification, treatment targets, hypoglycemia precautions, diabetes complications, and medication safety. There was a good understanding of these themes among patients with a higher educational attainment, however, among those with lower educational attainment, the attitude of patients toward diabetes care is paternalistic. Conclusion. The themes discussed in outpatient diabetes consult reflects the dimensions of diabetes care mainly influenced by socio-cultural factors, patient-doctor relationships and adaptability to limitations of resources. The results will be used to develop and validate a culturally appropriate diabetes health literacy tool.

Various families of ion channels have been characterized in mesenchymal stem cells (MSCs), including some members of transient receptor potential (TRP) channels family. TRP channels are involved in critical cellular processes as differentiation and cell proliferation. Here, we analyzed the expression of TRPM8 channel in human bone marrow MSCs (hBM-MSCs), and its relation with osteogenic differentiation. Patch-clamp recordings showed that hBM-MSCs expressed outwardly rectifying currents which were increased by exposure to 500 μM menthol and were partially inhibited by 10 μM of BCTC, a TRPM8 channels antagonist. Additionally, we have found the expression of TRPM8 by RT-PCR and western blot. We also explored the TRPM8 localization in hBM-MSCs by immunofluorescence using confocal microscopy. Remarkably, hBM-MSCs treatment with 100 μM of menthol or 10 μM of icilin, TRPM8 agonists, increases osteogenic differentiation. Conversely, 20 μM of BCTC, induced a decrease of osteogenic differentiation. These results suggest that TRPM8 channels are functionally active in hBM-MSCs and have a role in cell differentiation.

17β-estradiol is a neuronal survival factor against oxidative stress that triggers its protective effect even in the absence of classical estrogen receptors. The polymodal transient receptor potential vanilloid subtype 1 (TRPV1) channel has been proposed as a steroid receptor implied in tissue protection against oxidative damage. We show here that TRPV1 is sufficient condition for 17β-estradiol to enhance metabolic performance in injured cells. Specifically, in TRPV1 expressing cells, the application of 17β-estradiol within the first 3 h avoided H2O2-dependent mitochondrial depolarization and the activation of caspase 3/7 protecting against the irreversible damage triggered by H2O2. Furthermore, 17β-estradiol potentiates TRPV1 single channel activity associated with an increased open probability. This effect was not observed after the application of 17α-estradiol. We explored the TRPV1-Estrogen relationship also in primary culture of hippocampal-derived neurons and observed that 17β-estradiol cell protection against H2O2-induced damage was independent of estrogen receptors pathway activation, membrane started and stereospecific. These results support the role of TRPV1 as a 17β-estradiol-activated ionotropic membrane receptor coupling with mitochondrial function and cell survival.

Abstract Background Due to the post-mitotic nature of myonuclei, postnatal myogenesis is essential for skeletal muscle growth, repair, and regeneration. This process is facilitated by satellite cells through proliferation, differentiation, and subsequent fusion with a pre-existing muscle fiber (i.e., myonuclear accretion). Current knowledge of myogenesis is primarily based on the in vitro formation of syncytia from myoblasts, which represents aspects of developmental myogenesis, but may incompletely portray postnatal myogenesis. Therefore, we aimed to develop an in vitro model that better reflects postnatal myogenesis, to study the cell intrinsic and extrinsic processes and signaling involved in the regulation of postnatal myogenesis. Methods Proliferating C2C12 myoblasts were trypsinized and co-cultured for 3 days with 5 days differentiated C2C12 myotubes. Postnatal myonuclear accretion was visually assessed by live cell time-lapse imaging and cell tracing by cell labeling with Vybrant® DiD and DiO. Furthermore, a Cre/LoxP-based cell system was developed to semi-quantitatively assess in vitro postnatal myonuclear accretion by the conditional expression of luciferase upon myoblast–myotube fusion. Luciferase activity was assessed luminometrically and corrected for total protein content. Results Live cell time-lapse imaging, staining-based cell tracing, and recombination-dependent luciferase activity, showed the occurrence of postnatal myonuclear accretion in vitro. Treatment of co-cultures with the myogenic factor IGF-I (p

Abstract Background Sarcopenia is defined as the age‐related loss of skeletal muscle mass and function. While all humans lose muscle with age, 2–5% of elderly adults develop functional consequences (disabilities). The aim of this study was to investigate muscle myogenesis in healthy elderly adults, with or without sarcopenia, compared with middle‐aged controls using both in vivo and in vitro approaches to explore potential biomarker or causative molecular pathways associated with sarcopenic versus non‐sarcopenic skeletal muscle phenotypes during ageing. Methods Biomarkers of multiple molecular pathways associated with muscle regeneration were analysed using quantitative polymerase chain reaction in quadriceps muscle samples obtained from healthy elderly sarcopenic (HSE, n = 7) or non‐sarcopenic (HENS, n = 21) and healthy middle‐aged control (HMC, n = 22) groups. An in vitro system of myogenesis (using myoblasts from human donors aged 17–83 years) was used to mimic the environmental challenges of muscle regeneration over time. Results The muscle biopsies showed evidence of satellite cell activation in HENS (Pax3, P

Abstract Background Up to 60% of patients with bipolar disorder (BD) have a history of traumatic events, which is associated with greater episode severity, higher risk of comorbidity and higher relapse rates. Trauma-focused treatment strategies for BD are thus necessary but studies are currently scarce. The aim of this study is to examine whether Eye Movement Desensitization and Reprocessing (EMDR) therapy focusing on adherence, insight, de-idealisation of manic symptoms, prodromal symptoms and mood stabilization can reduce episode severity and relapse rates and increase cognitive performance and functioning in patients with BD. Methods/design This is a single-blind, randomized controlled, multicentre trial in which 82 patients with BD and a history of traumatic events will be recruited and randomly allocated to one of two treatment arms: EMDR therapy or supportive therapy. Patients in both groups will receive 20 psychotherapeutic sessions, 60 min each, during 6 months. The primary outcome is a reduction of affective episodes after 12 and 24 months in favour of the EMDR group. As secondary outcome we postulate a greater reduction in affective symptoms in the EMDR group (as measured by the Bipolar Depression Rating Scale, the Young Mania Rating Scale and the Clinical Global Impression Scale modified for BD), and a better performance in cognitive state, social cognition and functioning (as measured by the Screen for Cognitive Impairment in Psychiatry, The Mayer-Salovey-Caruso Emotional Intelligence Test and the Functioning Assessment Short Test, respectively). Traumatic events will be evaluated by The Holmes-Rahe Life Stress Inventory, the Clinician-administered PTSD Scale and the Impact of Event Scale. Discussion The results of this study will provide evidence whether a specific EMDR protocol for patients with BD is effective in reducing affective episodes, affective symptoms and functional, cognitive and trauma symptoms. Trial registration The trial is registered at ClinicalTrials.gov, identifier: NCT02634372 . Registered on 3 December 2015.

Allosteric interactions between the voltage-sensing domain (VSD), the Ca2+-binding sites, and the pore domain govern the mammalian Ca2+- and voltage-activated K+ (BK) channel opening. However, the functional relevance of the crosstalk between the Ca2+- and voltage-sensing mechanisms on BK channel gating is still debated. We examined the energetic interaction between Ca2+ binding and VSD activation by investigating the effects of internal Ca2+ on BK channel gating currents. Our results indicate that Ca2+ sensor occupancy has a strong impact on VSD activation through a coordinated interaction mechanism in which Ca2+ binding to a single α-subunit affects all VSDs equally. Moreover, the two distinct high-affinity Ca2+-binding sites contained in the C-terminus domains, RCK1 and RCK2, contribute equally to decrease the free energy necessary to activate the VSD. We conclude that voltage-dependent gating and pore opening in BK channels is modulated to a great extent by the interaction between Ca2+ sensors and VSDs.

Human granulocytic Anaplasmosis (HGA), is a tick-borne infectious disease transmitted by ticks, resulting in acute feverish episodes. The etiological agent is the bacteria Anaplasma phagocytophilum; which is spread by ticks of the genus Ixodes spp. to complete its life cycle. In Mexico, there is only one case report. The primary challenge is understanding how other bacteria affect or overlap with the clinical manifestation of the disease. Sample collection occurred over the period September 2017 through October 2019. Blood samples from human subjects were obtained immediately after they signed consent forms. We analyzed for the presence for A. phagocytophilum by serological (IFA IgG two times) and PCR targeting 16SrRNA and groEL genes, followed by DNA sequencing. All patients with a history of travel abroad were dismissed for this project. In total, 1924 patients participated and of these, 1014 samples across the country were analyzed. Of these, 85 (8.38%) had IFA results that ranged from 1:384 to 1:896. Of the positive samples, 7.10% were used for PCR. Significant clinical manifestations included: dizziness, nausea, petechial, epistaxis, enlarged liver and/or spleen and thrombocytopenia. Hospitalization of at least 1.5 days was necessary for 3.2% of patients. None of the cases analyzed were lethal. This is the first clinical manifestations along with serological test results and molecular analysis confirmed the presence of A. phagocytophilum resulting in HGA in patients from Mexico. Health institutions and medical practitioners in general should include diagnostic testing for HGA among high risk populations and should recognize it as a vector-borne emerging infectious disease in Mexico.

Objective: This present study aims to address the gap in the literature regarding the severity and underlying neural correlates of psychotic symptoms in frontotemporal dementia with and without the C9orf72 gene expansion. Methods: Fifty-six patients with behavioural variant frontotemporal dementia (20 with concomitant amyotrophic lateral sclerosis) and 23 healthy controls underwent neuropsychological assessments, detailed clinical interview for assessment of psychosis symptoms, brain MRI and genetic testing. Carers underwent a clinical interview based upon the neuropsychiatric inventory. Patients were assessed at ForeFront, the Frontotemporal Dementia Research Group at Neuroscience Research Australia or at the Brain and Mind Centre, between January 2008 and December 2013. An index of psychosis was calculated, taking into account the degree and severity of psychosis in each case. Voxel-based morphometry analyses were used to explore relationships between the psychosis index and grey matter changes. Results: Thirty-four percent of frontotemporal dementia patients showed psychotic features. C9orf72 expansion cases were more likely to exhibit psychotic symptoms than non-carriers (64% vs. 26%; p = 0.006), which were also more severe (psychotic index 23.1 vs. 8.1; p = 0.002). Delusions comprised persecutory, somatic, jealous and grandiose types and were present in 57% of C9orf72 carriers and 19% of non-carriers (p = 0.006). Auditory, visual or tactile hallucinations were present in 36% of C9orf72 carriers and 17% of non-carriers (p = 0.13). Increased psychotic symptoms in C9orf72 expansion carriers correlated with atrophy in a distributed cortical and subcortical network that included discrete regions of the frontal, temporal and occipital cortices, as well as the thalamus, striatum and cerebellum. Conclusions: This study underlines the need to consider and assess for psychotic symptoms in the frontotemporal dementia-amyotrophic lateral sclerosis continuum particularly in those with C9orf72 gene expansions. The network of brain regions identified in this study is strikingly similar to that identified in other psychotic disorders such as schizophrenia, which suggests that treatment strategies in psychiatry may be beneficial for the management of psychotic symptoms in frontotemporal dementia.

Peripheral artery disease (PAD) pathophysiology extends beyond hemodynamics to include other operating mechanisms, including endothelial dysfunction. Oxidative stress may be linked to endothelial dysfunction by reducing nitric oxide (NO) bioavailability. We aimed to investigate whether the NO system and its regulators are altered in the setting of PAD and to assess the relationship between NO bioavailability and oxidative stress. Sera from 35 patients with intermittent claudication (IC), 26 patients with critical limb ischemia (CLI), and 35 non-PAD controls were analyzed to determine levels of tetrahydrobiopterin (BH4), dihydrobiopterin (BH2), nitrate/nitrite (nitric oxides, or NOx), arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the oxidative stress markers 8-Oxo-2′-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE), advanced glycation end products (AGEs), and protein carbonyls. NOx was significantly lower in IC and CLI patients compared to controls in association with elevated oxidative stress, with the greatest NOx reductions observed in CLI. Compared with controls, IC and CLI patients had reduced BH4, elevated BH2, and a reduced BH4/BH2 ratio. SDMA, the arginine/SDMA ratio, and the arginine/ADMA ratio were significantly higher in CLI patients. The NO system and its regulators are significantly compromised in PAD. This dysregulation appears to be driven by increased oxidative stress and worsens as the disease progresses from claudication to CLI.

It is proposed to use the geographical potentialities of the Peonies lagoon scenario as a natural museum for the teaching of Physical Geography. The methodology is descriptive, projective, under a field design, not experimental. When diagnosing the «didactic resources», more than 80% of the respondents affirmed that the teacher does not use «directed and natural resources» in teaching. Regarding the «level of knowledge», there is weakness in the domain of the same, more than 75% of students did not succeed in the indicators «presence of lagoons», «presence of beaches and coastal dunes» and «sedimentation processes» of the Peonies lagoon. A proposal for a natural museum was designed based on the scenario of the referred lagoon, materialized in a guided tour that includes five (5) stations.

Se propone utilizar las potencialidades geográficas del escenario de la Laguna de las Peonías como museo natural para la enseñanza de la Geografía Física. La metodología es descriptiva, proyectiva, bajo un diseño de campo, no experimental. Al diagnosticar los “Recursos didácticos”, más del 80% de los encuestados afirma que el docente no utiliza “recursos dirigidos y naturales” en la enseñanza. Respecto al “nivel de conocimiento”, existe debilidad en el dominio del mismo, más del 75% de los estudiantes no acertaron en los indicadores “presencia de albuferas”, “presencia de playas y dunas costeras” y “procesos de sedimentación” de la Laguna de las Peonías. Se diseñó una propuesta de museo natural basado en el escenario de la referida laguna, materializado en una visita guiada que contempla cinco (5) estaciones.

Background: Eye movement desensitization and reprocessing [EMDR] is an innovative, evidence-based and effective psychotherapy for post-traumatic stress disorder [PTSD]. As with other psychotherapies, the effectiveness of EMDR contrasts with a limited knowledge of its underlying mechanism of action. In its relatively short life as a therapeutic option, EMDR has not been without controversy, in particular regarding the role of the bilateral stimulation as an active component of the therapy. The high prevalence of EMDR in clinical practice and the dramatic increase in EMDR research in recent years, with more than 26 randomized controlled trials published to date, highlight the need for a better understanding of its mechanism of action.Methods: We conducted a thorough systematic search of studies published until January 2018, using PubMed, ScienceDirect, Web of Knowledge and Scopus databases that examined the mechanism of action of EMDR or provided conclusions within the framework of current theoretical models of EMDR functioning.Results: Eighty-seven studies were selected for review and classified into three overarching models; (i) psychological models (ii) psychophysiological models and (iii) neurobiological models. The evidence available from each study was analyzed and discussed. Results demonstrated a reasonable empirical support for the working memory hypothesis and for the physiological changes associated with successful EMDR therapy. Recently, more sophisticated structural and functional neuroimaging studies using high resolution structural and temporal techniques are starting to provide preliminary evidence into the neuronal correlates before, during and after EMDR therapy.Discussion: Despite the increasing number of studies that published in recent years, the research into the mechanisms underlying EMDR therapy is still in its infancy. Studies in well-defined clinical and non-clinical populations, larger sample sizes and tighter methodological control are further needed in order to establish firm conclusions.

In dit onderzoek wordt ingegaan op de invloed van variabele beloningen voor de CEO en/of CFO op de verwerking van door de accountant geconstateerde controleverschillen. In dit onderzoek is geanalyseerd of een variabele beloning van invloed is op het constateren en het corrigeren van controleverschillen. Uit de onderzoeksresultaten volgt dat het aantal geconstateerde controleverschillen niet hoger is indien een variabele beloning aanwezig is. Uit de onderzoeksresultaten volgt voorts dat subjectieve controleverschillen minder vaak gecorrigeerd worden indien sprake is van variabele beloning. Aanvullend concluderen wij dat grotere controleverschillen minder vaak gecorrigeerd worden indien een variabele beloning aanwezig is. De gebruiker van de jaarrekening heeft doorgaans geen goed inzicht in de aard en omvang van niet-gecorrigeerde verschillen. Een mogelijke oplossing hiervoor is het vermelden van grotere niet-gecorrigeerde controleverschillen in de controleverklaring. Accountantsorganisaties kunnen overwegen bij een kwaliteitsonderzoek een specifiek aandachtspunt mee te nemen bij opdrachten waar sprake is van variabele managementbeloning.

RESUMEN La Ciencia del Suelo, constituye la base de problemáticas como cambio climático y desertificación. Los cuantiosos datos que proporcionan los estudios de suelos, componen información valiosa para satisfacer las demandas de la sociedad y las decisiones políticas. El desafío actual es lograr disponer de esa información de manera precisa, cuantitativa, accesible, comprensible y adecuarla a las necesidades de los nuevos requerimientos. En este sentido, se elaboró un proyecto para la informatización, evaluación, recomendación y control del suelo para su mejor utilización. Durante su ejecución se elaboró un diseño del sistema, a partir de los procesos fundamentales que dirigen los servicios científico técnico del Instituto de Suelo. Se obtuvo un Sistema Integrador de Datos de Suelo (SIDS), para el manejo eficiente de la información en la gestión de la agricultura ante los posibles cambios globales, en la producción de alimentos y conservación de la calidad del suelo. Este sistema lo conforman un paquete de software que integran y procesan la información (SARLAB, REGIFERT, SEMCAS y SIG MDS), para agilizar la respuesta del estado del suelo en el manejo de la agricultura, organizar el sistema de control, el flujo de la información del suelo y el incremento de la eficiencia económica. Soil computerized system agriculture management to climate change. ABSTRACT Soil Science is the basis of issues such as climate change and desertification. Voluminous data provided by soil studies, up valuable information to meet the demands of society and political decisions. The challenge is to have that information accurately, quantitative, accessible, understandable and adapt to the needs of the new requirements manner. In this regard, a project for the computerization, evaluation, recommendation and monitoring of soil for better utilization was developed. During execution system design was developed, based on the fundamental processes that drive the technical and scientific services of the Institute of Soil. Integrated System Soils Data (ISSD), for efficient management of information in the management of agriculture to the possible global changes in food production and conservation of soil quality was obtained. This system is made up of a software package that integrates and process information (SARLAB, REGIFERT, SEMCAS and GISMDS) to speed up the response of soil condition in the management of agriculture, organize the control system, the flow of soil information and increasing economic efficiency.

Eye Movement Desensitization and Reprocessing (EMDR) is considered highly efficacious for the treatment of Post-traumatic Stress Disorder and has proved to be a valid treatment approach with a wide range of applications. However, EMDR’s mechanisms of action is not yet fully understood. This is an active area of clinical and neurophysiological research, and several different hypotheses have been proposed. This paper discusses a conjecture which focuses on the similarity between the delta waves recorded by electroencephalography during Slow Wave Sleep (SWS) and those registered upon typical EMDR bilateral stimulation (eye movements or alternate tapping) during recurrent distressing memories of an emotionally traumatic event. SWS appears to have a key role in memory consolidation and in the reorganization of distant functional networks, as well as Eye Movements seem to reduce traumatic episodic memory and favor the reconsolidation of new associated information. The SWS hypothesis may put forward an explanation of how EMDR works, and is discussed also in light of other theories and neurobiological findings.

Este artículo analiza el papel de los impuestos municipales y en qué medida estos tributos hicieron subir los precios en torno a un 20% y bajar los salarios reales entre un 15 y un 20% en Madrid durante los años que median entre 1596 y 1700, resultados que bien pueden considerarse representativos de una tendencia general en las ciudades castellanas del siglo XVII. De un modo más general, los autores citados, utilizando documentación del Archivo Histórico Nacional, del Archivo General de Palacio y del Archivo General de Simancas, afirman que la suma del pago de los impuestos reales y de los impuestos municipales, es decir, de la fiscalidad en su conjunto, tuvo una decisiva influencia en la decadencia de la hasta entonces floreciente red urbana del reino castellano, pues, entre otras cosas, redujo la competitividad de las manufacturas que se fabricaban en dichas ciudades. Cualquier estudio de los impuestos cobrados por la villa durante este período conduce al análisis de las estrechas relaciones financieras entre la Corona y su capital. Para reunir la suma que Madrid otorgó a la Corona mediante donativos, la ciudad pidió prestadas estas cantidades. A cambio, la Real Hacienda transfirió a Madrid la mayor parte de los impuestos reales que se cobraban en la villa y su distrito fiscal, permitiendo también que Madrid introdujera nuevos impuestos municipales para pagar los intereses y amortizar el principal de las sumas tomadas en préstamo.

Esta investigación tiene como objetivo proponer el paisaje de la Laguna de Mucubají como recurso didáctico para la enseñanza de procesos y formas glaciales en la asignatura Ciencias de la Tierra. Se empleó una metodología descriptiva y proyectiva, bajo un diseño de campo y no experimental. Las técnicas utilizadas son observación, encuesta y revisión documental. En el diagnóstico de los “recursos didácticos”, más del 80% coincide en que el docente no utiliza recursos relacionados con la realidad, debido a la ausencia de recursos didácticos basados en paisajes naturales. En los resultados de “nivel de conocimiento”, más del 60% de los encuestados desacertó en los ítems referidos a formas de erosión y formas de acumulación glacial, lo que denota debilidad en el dominio del conocimiento. Se elaboró un paquete didáctico basado en el paisaje de la Laguna de Mucubají con la finalidad de estimular en los estudiantes el aprendizaje de procesos geomorfológicos. Palabras clave Laguna de Mucubají, recursos didácticos, paisaje natural, procesos y formas glaciales Mucubají’s Lagoon. Didactic Offer for Teaching Geomorphologic Processes from the Sciences of the Earth Abstract This investigation has as its aim propose the landscape of Mucubají's Lagoon as a didactic resource for the education of glacial processes and forms in the subject Sciences of the Earth. A descriptive and projective methodology was used, under a field design and not experimental. The techniques used are observation, survey and documentary review. In the diagnosis of the “didactic resources", more than 80% agreed that the teacher did not use resources related to reality, due to the absence of didactic resources based on natural landscapes. In the results of “level of knowledge", more than 60 % of respondents were wrong in the items referred to the erosion forms and accumulation of glacial forms, which denotes weaknesses in the domain of knowledge, according to scale of interpretation used. There was elaborated a didactic package based on the landscape of Mucubají's Lagoon with the purpose of stimulating the students to the learning of geomorphologic processes. Keywords Mucubají's Lagoon, didactic resources, natural landscape, processes and glacial forms

Con el objetivo de determinar o no la presencia en el tomate de algunos virus en la enfermedad denominada "acolochamiento"del tomate y si son o no transmitidos por la mosca blanca (Bemisia tabaci Gennadius), se realizó un muestreo en los departamentos de Zaeapa, Jutiapa, Jalapa, Chimaltenango y Guatemala. Se detectó la presencia de seis virus: TMV, CMV, TEV, PVY, PVX y TSWV; y dos geminivirus CdTV y SCLV. La presencia de una sola muestra positiva para TSWV, es dudosa y es necesario reconfirmar o no su presencia en Guatemala, porque hasta el momento no había sido informado en el país, Así mismo, los geminivirus en el tomate, no se tenían informes en Guatemala, de su presencia, caso del Virus Chino del tomate (VCdT) y del Virus del enrollamiento de la hoja del Ayote (SCLV), Así mismo se concluyó que en "el acolochamiento" del tomate, están asociados virus diferentes y que son la causa de la diversidad de síntomas de esta enfermedad.