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Optimizing pain management in spinal surgery is crucial for preventing adverse events due to delayed mobilization. Magnesium sulfate has potential benefits in spinal surgery because of its analgesic properties and modulation of neurotransmitters and autonomic nervous system. Existing evidence regarding the use of magnesium sulfate is partial and controversial, necessitating a comprehensive meta-analysis to evaluate its efficacy and safety. The aim of this study was to conduct a comprehensive meta-analysis to evaluate the efficacy and safety of magnesium sulfate in spinal surgery compared to other available options. This meta-analysis adhered to the PRISMA guidelines. Patients undergoing spinal surgery were included, with the intervention group receiving intravenous magnesium sulfate (MS) at various doses or combinations, whereas the comparison group received other alternatives or a placebo. The efficacy and safety outcomes were assessed. Data were collected from multiple databases and analyzed using Review Manager version 5.4. Heterogeneity was assessed and fixed- or random-effects models were applied. The meta-analysis included eight studies (n = 541). Magnesium sulfate demonstrated significant reductions in pain at 24 h (MD -0.20, 95% CI: -0.39 to -0.02) and opioid consumption (SMD -0.66, 95% CI: -0.95 to -0.38) compared to placebo. Additionally, a decrease in the use of muscle relaxants (SMD -0.91, 95% CI: -1.65 to -0.17) and remifentanil (SMD -1.52, 95% CI: -1.98 to -1.05) was observed. In contrast, an increase in extubation time (MD 2.42, 95% CI: 1.14 to 3.71) and verbal response (MD 1.85, 95% CI: 1.13 to 2.58) was observed compared to dexmedetomidine. In conclusion, magnesium sulfate administration in spinal surgery reduced pain and opioid consumption, and prolonged orientation and verbal response. No significant differences in blood pressure or heart rate were observed between the groups.
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Rhodococcus erythropolis bacterium is known for its remarkable resistance characteristics that can be useful in several biotechnological processes, such as bioremediation. However, there is scarce knowledge concerning the behavior of this strain against different metals. This study sought to investigate the behavior of R. erythropolis ATCC 4277 against the residue of chalcopyrite and e-waste to verify both resistive capacities to the metals present in these residues and their potential use for biomining processes. These tests were carried out in a stirred tank bioreactor for 48 h, at 24ºC, pH 7.0, using a total volume of 2.0 L containing 2.5% (v/v) of a bacterial pre-culture. The pulp density of chalcopyrite was 5% (w/w), and agitation and oxygen flow rates were set to 250 rpm and 1.5 LO2 min-1, respectively. On the other hand, we utilized a waste of computer printed circuit board (WPCB) with a pulp density of 10% (w/w), agitation at 400 rpm, and an oxygen flow rate of 3.0 LO2 min-1. Metal concentration analyses post-fermentation showed that R. erythropolis ATCC 4277 was able to leach about 38% of the Cu present in the chalcopyrite residue (in ~ 24 h), and 49.5% of Fe, 42.3% of Ni, 27.4% of Al, and 15% Cu present in WPCB (in ~ 24 h). In addition, the strain survived well in the environment containing such metals, demonstrating the potential of using this bacterium for waste biomining processes as well as in other processes with these metals.
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Apicomplexans are a diverse phylum of unicellular eukaryotes that share obligate relationships with terrestrial and aquatic animal hosts. Many well-studied apicomplexans are responsible for several deadly zoonotic and human diseases, most notably malaria caused by Plasmodium. Interest in the evolutionary origin of apicomplexans has also spurred recent work on other more deeply-branching lineages, especially gregarines and sister groups like squirmids and chrompodellids. But a full picture of apicomplexan evolution is still lacking several lineages, and one major, diverse lineage that is notably absent is the adeleorinids. Adeleorina apicomplexans comprises hundreds of described species that infect invertebrate and vertebrate hosts across the globe. Although historically considered coccidians, phylogenetic trees based on limited data have shown conflicting branch positions for this subgroup, leaving this question unresolved. Phylogenomic trees and large-scale analyses comparing cellular functions and metabolism between major subgroups of apicomplexans have not incorporated Adeleorina because only a handful of molecular markers and a couple organellar genomes are available, ultimately excluding this group from contributing to our understanding of apicomplexan evolution and biology. To address this gap, we have generated complete genomes from mitochondria and plastids, as well as multiple deep-coverage single-cell transcriptomes of nuclear genes from two Adeleorina species, Klossia helicina and Legerella nova, and inferred a 206-protein phylogenomic tree of Apicomplexa. We observed distinct structures reported in species descriptions as remnant host structures surrounding adeleorinid oocysts. Klossia helicina and L. nova branched, as expected, with monoxenous adeleorinids within the Adeleorina and their mitochondrial and plastid genomes exhibited similarity to published organellar adeleorinid genomes. We show with a phylogeneomic tree and subsequent phylogenomic analyses that Adeleorina are not closely related to any of the currently sampled apicomplexan subgroups, and instead fall as a sister to a large clade encompassing Coccidia, Protococcidia, Hematozoa, and Nephromycida, collectively. This resolves Adeleorina as a key independently-branching group, separate from coccidians, on the tree of Apicomplexa, which now has all known major lineages sampled.
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Apicomplexa , Genoma de Plastidios , Animales , Humanos , Filogenia , Plastidios/genética , Genoma , Apicomplexa/genéticaRESUMEN
With Europe's ageing population and rising demand for palliative care, it is crucial to examine the use of palliative care among older adults during their last years of life and understand the factors influencing their access and end-of-life circumstances. This study employed a cohort of SHARE participants aged 65 years or older who had passed away between Wave 6 (2015) and Wave 7 (2017). Information on death circumstances, palliative care utilization, and associated variables were analysed. The study revealed that nearly 13.0% of individuals across these countries died under palliative care, with Slovenia having the lowest rate (0.3%) and France the highest (30.4%). Palliative care utilization in the last 30 days before death was observed in over 24.0% of participants, with the Czech Republic having the lowest rate (5.0%) and Greece the highest (48.8%). A higher risk of using or dying in palliative care was significantly associated with cognitive impairment (low verbal fluency), physical inactivity, and good to excellent self-perceived health. This work highlights the urgent need for enhanced global access to palliative care and advocates for the cross-country comparison of effective practices within Europe, tailored to the unique healthcare needs of older adults.
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Envejecimiento , Cuidados Paliativos , Humanos , Anciano , Cuidados Paliativos/psicología , Envejecimiento/psicología , Europa (Continente)/epidemiología , República Checa/epidemiología , Instituciones de SaludRESUMEN
Granulomas are important immunological structures in the host defense against the fungus Paracoccidioides brasiliensis, the main etiologic agent of Paracoccidioidomycosis (PCM), a granulomatous systemic mycosis endemic in Latin America. We have performed transcriptional and proteomic studies of yeasts present in the pulmonary granulomas of PCM aiming to identify relevant genes and proteins that act under stressing conditions. C57BL/6 mice were infected with 1x106 yeasts and after 8- and 12-weeks of infection, granulomatous lesions were obtained for extraction of fungal and murine RNAs and fungal proteins. Dual transcriptional profiling was done comparing lung cells and P. brasiliensis yeasts from granulomas with uninfected lung cells and the original yeast suspension used in the infection, respectively. Mouse transcripts indicated a lung malfunction, with low expression of genes related to muscle contraction and organization. In addition, an increased expression of transcripts related to the activity of neutrophils, eosinophils, macrophages, lymphocytes as well as an elevated expression of IL-1ß, TNF-α, IFN-γ, IL-17 transcripts were observed. The increased expression of transcripts for CTLA-4, PD-1 and arginase-1, provided evidence of immune regulatory mechanisms within the granulomatous lesions. Also, our results indicate iron as a key element for the granuloma to function, where a high number of transcripts related to fungal siderophores for iron uptake was observed, a mechanism of fungal virulence not previously described in granulomas. Furthermore, transcriptomics and proteomics analyzes indicated a low fungal activity within the granuloma, as demonstrated by the decreased expression of genes and proteins related to energy metabolism and cell cycle.
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Paracoccidioides , Paracoccidioidomicosis , Animales , Ratones , Paracoccidioides/genética , Proteómica , Ratones Endogámicos C57BL , Hierro/metabolismo , Inmunidad , GranulomaRESUMEN
Approximately 25% to 35% of individuals diagnosed with an autism spectrum disorder (ASD) do not acquire vocal speech and may require an augmentative and alternative communication (AAC) modality to express their wants and needs. There are various modes of AAC that individuals with limited vocal speech may use (e.g., manual signs, picture cards). However, the process used to identify the most appropriate communication modality for an individual is not always systematic. Thus, the acquisition of the specified AAC modality may be slow if the communication modality prescribed is inappropriate. To date, there are a few methods that may be used to select an AAC modality. However, these methods consider different variables. For example, McGreevy et al. (2014) included a communication assessment within the Essential for Living (EFL) manual that identifies and ranks appropriate AAC modalities for individuals. Nevertheless, to date, there is no research demonstrating that individuals will acquire the communication modality recommended by the EFL or comparing acquisition of this AAC modality to other frequently used AACs. Thus, this study aimed to compare acquisition of mands across three AACs, evaluate whether mands taught using the AAC modality recommended by the EFL were acquired in fewer sessions, and determine whether participants preferred the AAC modality acquired in fewer sessions. Four children diagnosed with ASD and limited vocal repertoires participated in this study. All participants acquired mands using the AAC modality recommended by the EFL. However, for all participants, rate of acquisition was similar across all three modalities of AAC and preference of AAC was idiosyncratic.
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Pyridoxal 5'-phosphate (PLP)-dependent enzymes utilize a vitamin B6-derived cofactor to perform a myriad of chemical transformations on amino acids and other small molecules. Some PLP-dependent enzymes, such as serine hydroxymethyltransferase (SHMT), are promising drug targets for the design of small-molecule antimicrobials and anticancer therapeutics, while others have been used to synthesize pharmaceutical building blocks. Understanding PLP-dependent catalysis and the reaction specificity is crucial to advance structure-assisted drug design and enzyme engineering. Here we report the direct determination of the protonation states in the active site of Thermus thermophilus SHMT (TthSHMT) in the internal aldimine state using room-temperature joint X-ray/neutron crystallography. Conserved active site architecture of the model enzyme TthSHMT and of human mitochondrial SHMT (hSHMT2) were compared by obtaining a room-temperature X-ray structure of hSHMT2, suggesting identical protonation states in the human enzyme. The amino acid substrate serine pathway through the TthSHMT active site cavity was tracked, revealing the peripheral and cationic binding sites that correspond to the pre-Michaelis and pseudo-Michaelis complexes, respectively. At the peripheral binding site, the substrate is bound in the zwitterionic form. By analyzing the observed protonation states, Glu53, but not His residues, is proposed as the general base catalyst, orchestrating the retro-aldol transformation of L-serine into glycine.
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Digital Health is a subject of extensive discourse when considering its current and future significance. This significance arises from a convergence of various factors, including the escalating capabilities and cost-effectiveness of computing and communication technology, coupled with the mounting demands and challenges faced by healthcare systems. The integration of health and technology, when studied collectively with the purpose of addressing tangible real-world issues, holds the potential to generate substantial outcomes that greatly influence the provision of clinical and social care, thereby enhancing the overall well-being of both individuals and populations. In this sense, in this paper we propose a collaborative approach, using Open Innovation, where the most relevant stakeholders-health and care professionals, citizens and companies-work together to develop and validate innovative digital solutions for health and care. We have called this approach of value co-creation the Collaborative Ecosystem, and we focus specifically on the potential development of the Regional Ecosystem for Collaborative Innovation in Digital Health and Care, and the envisioned implications of its implementation in economic and social dimensions.
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For the first time, the International Symposium on Fungal Stress was joined by the XIII International Fungal Biology Conference. The International Symposium on Fungal Stress (ISFUS), always held in Brazil, is now in its fourth edition, as an event of recognized quality in the international community of mycological research. The event held in São José dos Campos, SP, Brazil, in September 2022, featured 33 renowned speakers from 12 countries, including: Austria, Brazil, France, Germany, Ghana, Hungary, México, Pakistan, Spain, Slovenia, USA, and UK. In addition to the scientific contribution of the event in bringing together national and international researchers and their work in a strategic area, it helps maintain and strengthen international cooperation for scientific development in Brazil.
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Biología , Brasil , Francia , España , MéxicoRESUMEN
The Department of Veterans Health Affairs (VHA) has launched 22 multispecialty post-COVID-19 clinics across the US for the growing number of veterans experiencing long-term sequelae after acute COVID-19 infection. While evidence-based treatments for this syndrome are under investigation, there is a critical need to establish and disseminate clinical pathways (CPWs) based on knowledge and experience gained in those clinics. This VHA CPW is intended to guide primary care clinicians who care for patients experiencing dyspnea and/or cough during post-COVID-19 syndrome (PCS), which includes symptoms and abnormalities persisting or present beyond 12 weeks of the onset of acute COVID-19. This effort will help guide and standardize the care of veterans across the VHA, improve health outcomes, and effectively utilize health care resources. This article summarizes our stepwise diagnostic approach for patients presenting with PCS dyspnea and/or cough in primary care; it also highlights teleconsultation and telerehabilitation as opportunities to reach those in rural areas or with transportation barriers and improve reach for specialized services.
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Garambullo (Myrtillocactus geometrizans) is endemic in México, and although popularly consumed locally, its nutritional characteristics and value have not been studied in details. The objective of this work was to investigate the bioactive compounds and antioxidant activity in garambullo fruit from different sites at three ripening stages. Fruit from the three ripening stages (red, purple, and dark purple) were investigated for their physicochemical characteristics, hydrophilic (phenolic compounds, betalains, and ascorbic acid), and lipophilic (carotenoids, tocopherols, and fatty acids) bioactive compounds, using spectrophotometry, gas chromatography (GC-FID), and high-pressure liquid chromatography coupled to mass spectrometry (HPLC/DAD-ESI-MS). The antioxidant capacity was measured with the 2,2'-diphenyl-1-picrylhydrazyl and the ferric-ion-reducing antioxidant power assays. The color components of the fruit, chroma and a* values increased, whereas lightness (L*) and b* significantly decreased during ripening. Five betacyanins and four betaxanthins were tentatively identified with HPLC/DAD-ESI-MS, and betacyanins were more abundant than betaxanthins. Betalains content and antioxidant capacity of hydrophilic extracts significantly increased during ripening. Ten phenolic compounds were identified, with ferulic acid being the most abundant. Tocopherols were low (0.023-0.033 mg/100 g fw). Five fatty acids were abundant, and linoleic acid was the most important. Phenolic compounds, ascorbic acid, total carotenoids, and fatty acids decreased during fruit ripening. Garambullo fruit is rich in phytochemical compounds of importance for human nutrition and health. PRACTICAL APPLICATION: The physicochemical and bioactive compounds characterization in garambullo fruit is important to establish maturation and harvesting indices, postharvest strategies to preserve fruit quality and prolong postharvest life, promote the consumption and utilization of the fruit, and the designing of proper functional foods. In addition, the knowledge on the bioactive components might be useful to include this fruit in personalized nutritional approaches for patients with risks of certain chronic diseases. The methodology used in this study could be useful for the study of other fruits, especially those from the Cactaceae family.
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Antioxidantes , Cactaceae , Humanos , Antioxidantes/análisis , Frutas/química , Betacianinas/análisis , Betaxantinas/análisis , Cromatografía de Gases y Espectrometría de Masas , Cactaceae/química , Betalaínas/análisis , Ácido Ascórbico/análisis , Fenoles/análisis , Tocoferoles/análisis , Carotenoides/análisis , Extractos Vegetales/químicaRESUMEN
Genetic counseling and testing (GCT) inform cancer management for persons at risk for hereditary breast and ovarian cancer (HBOC). Community-based organizations (CBOs) may play a role in identifying at-risk Latinx individuals to connect them to GCT but data are lacking. Two academic centers and their four CBO partners planned to implement a validated questionnaire for HBOC risk screening ("HBOC risk screening tool"). This study aimed to assess CBO's preferences for HBOC risk screening tools, as well as the barriers and facilitators anticipated for future implementation. Pre-implementation focus groups were conducted with CBO's staff. Discussions centered on current practices to identify and refer at-risk patients. During the discussion, staff were asked to select one out of five validated HBOC risk screening tools to implement and to discuss anticipated barriers/facilitators for implementation. The four focus groups were coded and qualitative analyzed following the Consolidated Framework for Implementation Research (CFIR) and Health Equity domains. All CBOs chose the Family History Screen 7 (FHS-7). Participants (N = 35) highlighted how the FHS-7 was easy to adapt to better fit the target population and changing guidelines. They had positive attitudes toward implementing the screening tool, stressed how the culture of the organization positioned them to reach the target population, and noted barriers in different CFIR domains (e.g., low knowledge about HBOC and GCT referrals; scarce available resources). Participants pointed to barriers related to health equity domains including limited access to GCT and follow-up care for uninsured and underinsured populations, challenges obtaining accurate family history, and immigration-related barriers. CBOs highlighted the importance of partnering with other stakeholders to overcome barriers. Findings emphasize the need to develop multi-level implementation strategies to overcome barriers and leverage facilitators. This study can inform the development of implementation toolkits for CBOs to implement HBOC screening tools to advance health equity.
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Neoplasias de la Mama , Equidad en Salud , Neoplasias Ováricas , Humanos , Femenino , Detección Precoz del Cáncer , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/genética , Investigación Cualitativa , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genéticaRESUMEN
BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) concentrations (<30 ng/mL [<50 nmol/L]) have been associated with muscle weakness and impaired physical performance in observational studies. However, the effect of vitamin D supplementation on changes in muscle strength and physical performance in randomized controlled trials has been mixed. OBJECTIVES: To determine the effect of daily vitamin D supplementation on leg power, strength, and physical performance in low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL. METHODS: In this double-blind, randomized controlled trial, 136 low-functioning [Short Physical Performance Battery (SPPB) scores ≤10] adults aged 65-89 y with 25(OH)D concentrations of 18 to <30 ng/mL were randomly assigned to 2000 IU/d vitamin D3 or placebo for 12 mo. Lower-extremity leg power (primary outcome), leg and grip strength, SPPB, timed up and go (TUG), postural sway, and gait velocity and spatiotemporal parameters (secondary outcomes) were assessed at baseline, 4 and 12 mo. A subset (n = 37) also underwent a muscle biopsy at baseline and 4 mo and muscle fiber composition and contractile properties were assessed. RESULTS: Participants' mean ± SD age and SPPB scores at baseline were 73.4 ± 6.3 y and 7.8 ± 1.8, respectively. Mean ± SD 25(OH)D concentrations at baseline and 12 mo were 19.4 ± 4.2 ng/mL and 28.6 ± 6.7 ng/mL in the vitamin D group and 19.9 ± 4.9 ng/mL and 20.2 ± 5.0 ng/mL in the placebo group for a mean ± SE difference of 9.1 ± 1.1 ng/mL (P < 0.0001). However, there were no differences in change in leg power, leg or grip strength, SPPB score, TUG, postural sway, or gait velocity and spatiotemporal parameters by intervention group over 12 mo or muscle fiber composition and contractile properties over 4 mo. CONCLUSIONS: In low-functioning older adults with 25(OH)D concentrations of 18 to <30 ng/mL, randomization to 2000 IU/d vitamin D3 did not result in improvements in leg power, strength, or physical performance or muscle fiber composition and contractile properties. This trial was registered at clinicaltrials.gov as NCT02015611.
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Suplementos Dietéticos , Deficiencia de Vitamina D , Humanos , Anciano , Vitamina D , Vitaminas , Colecalciferol , Fuerza Muscular , Método Doble Ciego , Rendimiento Físico Funcional , Músculos , Deficiencia de Vitamina D/tratamiento farmacológico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Practical experiments drive important scientific discoveries in biology, but theory-based research studies also contribute novel-sometimes paradigm-changing-findings. Here, we appraise the roles of theory-based approaches focusing on the experiment-dominated wet-biology research areas of microbial growth and survival, cell physiology, host-pathogen interactions, and competitive or symbiotic interactions. Additional examples relate to analyses of genome-sequence data, climate change and planetary health, habitability, and astrobiology. We assess the importance of thought at each step of the research process; the roles of natural philosophy, and inconsistencies in logic and language, as drivers of scientific progress; the value of thought experiments; the use and limitations of artificial intelligence technologies, including their potential for interdisciplinary and transdisciplinary research; and other instances when theory is the most-direct and most-scientifically robust route to scientific novelty including the development of techniques for practical experimentation or fieldwork. We highlight the intrinsic need for human engagement in scientific innovation, an issue pertinent to the ongoing controversy over papers authored using/authored by artificial intelligence (such as the large language model/chatbot ChatGPT). Other issues discussed are the way in which aspects of language can bias thinking towards the spatial rather than the temporal (and how this biased thinking can lead to skewed scientific terminology); receptivity to research that is non-mainstream; and the importance of theory-based science in education and epistemology. Whereas we briefly highlight classic works (those by Oakes Ames, Francis H.C. Crick and James D. Watson, Charles R. Darwin, Albert Einstein, James E. Lovelock, Lynn Margulis, Gilbert Ryle, Erwin R.J.A. Schrödinger, Alan M. Turing, and others), the focus is on microbiology studies that are more-recent, discussing these in the context of the scientific process and the types of scientific novelty that they represent. These include several studies carried out during the 2020 to 2022 lockdowns of the COVID-19 pandemic when access to research laboratories was disallowed (or limited). We interviewed the authors of some of the featured microbiology-related papers and-although we ourselves are involved in laboratory experiments and practical fieldwork-also drew from our own research experiences showing that such studies can not only produce new scientific findings but can also transcend barriers between disciplines, act counter to scientific reductionism, integrate biological data across different timescales and levels of complexity, and circumvent constraints imposed by practical techniques. In relation to urgent research needs, we believe that climate change and other global challenges may require approaches beyond the experiment.
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Inteligencia Artificial , COVID-19 , Humanos , Pandemias , Control de Enfermedades Transmisibles , FilosofíaRESUMEN
Telephone genetic counseling (TGC) is accepted as standard clinical care for people seeking hereditary cancer risk assessment. TGC has been shown to be non-inferior to in-person genetic counseling, but trials have been conducted with a predominantly highly educated, non-Hispanic White population. This article describes the process of culturally adapting a TGC protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at risk for hereditary breast and ovarian cancers. The adaptation process included two phases. Phase 1 involved a review of the literature and recommendations from an expert team including community partners. Phase 2 included interviews and a pilot with the target population (n = 14) to collect feedback about the adapted protocol and booklet following steps from the Learner Verification and Revision Framework. We describe the adaptation process and report the main adaptations following the Framework for Reporting Adaptations and Modifications to Evidence-based Interventions (FRAME). Adaptations in Phase 1 were responsive to the target population needs and characteristics (e.g., delivered in Spanish at an appropriate health literacy level, addressing knowledge gaps, targeting cultural values). Phase 2 interviews were crucial to refine details (e.g., selecting words) and to add components to address GCT barriers (e.g., saliva sample video). Cultural adaptations to evidence-based TGC protocols can increase the fit and quality of care for historically underserved populations. As TGC visits become routine in clinical care, it is crucial to consider the needs of diverse communities to adequately promote equity and justice in cancer care.
This article describes the process of adapting a telephone genetic counseling protocol and visual aid booklet for Spanish-preferring Latina breast cancer survivors at increased risk for hereditary breast and ovarian cancer (HBOC). The cultural adaptation process followed two phases. In the first phase, the authors reviewed the literature and obtained insights from interdisciplinary experts. In the second phase, the authors received iterative feedback from fourteen Latina women who were breast cancer survivors, spoke Spanish as a first language, and met criteria to be considered at increased risk for HBOC. Revisions to the protocol and visual aid booklet were conducted iteratively following feedback from the expert team, after the first five women reviewed the booklet, after the second five women reviewed the booklet, and after the final four women completed the entire culturally adapted telephone genetic counseling protocol with the booklet. The final adaptations to the protocol and visual aid booklet were responsive to the target population's needs. Most adaptations made were regarding content. For example, simplifying the material presented, adding culturally relevant images, and developing a video explaining how to collect a saliva sample. Culturally adapting health interventions can improve health outcomes in historically marginalized populations and promote equity.
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Neoplasias de la Mama , Supervivientes de Cáncer , Neoplasias Ováricas , Humanos , Femenino , Asesoramiento Genético/psicología , Neoplasias de la Mama/genética , Neoplasias de la Mama/psicología , Folletos , Neoplasias Ováricas/genética , Hispánicos o Latinos/psicología , Teléfono , Literatura de Revisión como AsuntoRESUMEN
Toxoplasma gondii (T. gondii) is a zoonotic apicomplexan parasite that is an important cause of clinical disability in humans. On a global scale, one third of the human population is infected with T. gondii. Mice and other small rodents are believed to be responsible for transmission of T. gondii to the domestic cat, its definitive host. Interferon-inducible Immunity-Related GTPases (IRG proteins) are important for control of murine T. gondii infections. Virulence differences between T. gondii strains are linked to polymorphic rhoptry proteins (ROPs) that cooperate to inactivate individual IRG family members. In particular, the pseudokinase ROP5 isoform B is critically important in laboratory strains of mice. We identified T. gondii ROP39 in complex with ROP5B and demonstrate its contribution to acute T. gondii virulence. ROP39 directly targets Irgb10 and inhibits homodimer formation of the GTPase leading to an overall reduction of IRG protein loading onto the parasitophorous vacuolar membrane (PVM). Maintenance of PVM integrity rescues the parasite from IRG protein-mediated clearance in vitro and in vivo. This study identifies a novel T. gondii effector that is important for specific inactivation of the IRG resistance system. Our data reveal that yet unknown T. gondii effectors can emerge from identification of direct interaction partners of ROP5B.
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Parásitos , Toxoplasma , Toxoplasmosis , Animales , Ratones , Humanos , Gatos , Toxoplasma/metabolismo , Parásitos/metabolismo , Virulencia , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , GTP Fosfohidrolasas/metabolismoRESUMEN
Due to its relationship with oxidative stress and inflammation responses, obesity and its cardiometabolic implications have been related with serum copper (Cu). Hence, we analyzed the association of overweight (OW) and obesity (OB) status and cardiometabolic traits with serum Cu level in Mexican schoolchildren. Anthropometrical data and cardiometabolic traits were analyzed in this cross-sectional study. Serum Cu level was measured by inductively coupled plasma mass spectrometry. The study involved 191 schoolchildren (93 girls and 98 boys) with a mean age of 8.054 ± 1.170 years. Children with OW and OB had higher serum Cu levels than children with normal weight (NW) (mean difference: OW vs NW = 51.85 µg dL-1, OB vs NW = 47.22 µg dL-1, p < 0.001). In a multiple linear regression model, OW and OB status were positively associated with serum Cu levels (ßOW = 49.85, 95% confidence interval (95% CI) 35.84-63.87, p < 0.001; ßOB = 44.38, 95% CI 27.70-61.05, p < 0.001). We did not identify any significant association between cardiometabolic traits and serum Cu level. In conclusion, our results show an association of the presence of OW and OB with higher serum Cu levels, for the first time in Mexican schoolchildren. However, further functional studies are needed to better understand the role of Cu in the pathophysiology of obesity.
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Enfermedades Cardiovasculares , Sobrepeso , Masculino , Niño , Femenino , Humanos , Cobre , Estudios Transversales , Índice de Masa Corporal , ObesidadRESUMEN
Selenium (Se) is an essential trace element that by its antioxidant properties has been studied to elucidate its participation in the development of obesity and type 2 diabetes. We evaluated the association between cardiometabolic traits and serum Se levels in a sample of adults from southern Mexico. In 96 nondiabetic individuals, anthropometric data and clinical biochemistry measurements were analyzed. Serum total Se levels were measured with inductively coupled plasma mass spectrometry (ICP-MS). Serum Se level in the whole sample was 10.309 ± 3.031 µg mL-1 and no difference between the women and men was observed (p = 0.09). Additionally, fasting plasma glucose (FPG) was significantly associated with serum Se level (ß = -0.07 ± 0.03, p = 0.02, analysis adjusted for age, sex and BMI). Furthermore, sex shows significant interaction with FPG on the serum Se levels (p = 0.01). A follow-up analysis revealed the particular association between FPG and Se levels in women (ß = -0.10 ± 0.04, p = 0.01). In conclusion, our data evidenced a women-specific association between FPG and serum Se levels in a sample of adults from southern Mexico.
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The reinforcing characteristics of e-cigarettes could moderate the impact of reducing cigarette nicotine content. In this study, people who smoke daily were recruited from North Carolina and Pennsylvania (US) in 2018 and 2019. Within a randomized 2 × 2 × 2 factorial design, participants received investigational cigarettes and an e-cigarette for 12 weeks. Cigarette nicotine content was very low (0.4 mg/g of tobacco; VLNC) or normal (15.8 mg/g; NNC). E-liquids were 0.3% ("low") or 1.8% ("moderate") freebase nicotine, and available in tobacco flavors or tobacco, fruit, dessert and mint flavors. Study recruitment concluded before reaching the planned sample size (N = 480). Fifty participants were randomized and 32 completed the study. We found that randomization to VLNC, relative to NNC cigarettes, reduced self-reported cigarettes per day (CPD; mean difference: -12.96; 95% CI: -21.51, -4.41; p = 0.005); whereas e-liquid nicotine content and flavor availability did not have significant effects. The effect of cigarette nicotine content was larger in the moderate vs. low nicotine e-liquid groups and in the all flavors versus tobacco flavors e-liquid groups; tests of the interaction between e-liquid characteristics and cigarette nicotine content were not significant. Biomarkers of smoke exposure at Week 12 did not differ across conditions, which may reflect variability in adherence to only using VLNC cigarettes. In conclusion this study offers preliminary evidence that the extent to which cigarette nicotine reduction decreases smoking may depend on the reinforcing characteristics of alternative products, including the available nicotine contents and flavors of e-cigarettes.