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To improve the biocompatibility and bioactivity of biodegradable iron-based materials, nanostructured surfaces formed by metal oxides offer a promising strategy for surface functionalization. To explore this potential, iron oxide nanotubes were synthesized on pure iron (Fe) using an anodic oxidation process (50 V-30 min, using an ethylene glycol solution containing 0.3% NH4F and 3% H2O, at a speed of 100 rpm). A nanotube layer composed mainly of α-Fe2O3 with diameters between 60 and 70 nm was obtained. The effect of the Fe-oxide nanotube layer on cell viability and morphology was evaluated by in vitro studies using a human osteosarcoma cell line (SaOs-2 cells). The results showed that the presence of this layer did not harm the viability or morphology of the cells. Furthermore, cells cultured on anodized surfaces showed higher metabolic activity than those on non-anodized surfaces. This research suggests that growing a layer of Fe oxide nanotubes on pure Fe is a promising method for functionalizing and improving the cytocompatibility of iron substrates. This opens up new opportunities for biomedical applications, including the development of cardiovascular stents or osteosynthesis implants.
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Pseudomonas aeruginosa , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Aldeído Oxirredutases/metabolismo , Aldeído Oxirredutases/genética , Aldeído Oxirredutases/químicaRESUMO
Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.
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Abnormal tau accumulation is the hallmark of several neurodegenerative diseases, named tauopathies. Strategies aimed at reducing tau in the brain are promising therapeutic interventions, yet more precise therapies would require targeting specific nuclei and neuronal subpopulations affected by disease while avoiding global reduction of physiological tau. Here, we developed artificial microRNAs directed against the human MAPT mRNA to dwindle tau protein by engaging the endogenous RNA interference pathway. In human differentiated neurons in culture, microRNA-mediated tau reduction diminished neuronal firing without affecting neuronal morphology or impairing axonal transport. In the htau mouse model of tauopathy, we locally expressed artificial microRNAs in the prefrontal cortex (PFC), an area particularly vulnerable to initiating tau pathology in this model. Tau knockdown prevented the accumulation of insoluble and hyperphosphorylated tau, modulated firing activity of putative pyramidal neurons, and improved glucose uptake in the PFC. Moreover, such tau reduction prevented cognitive decline in aged htau mice. Our results suggest target engagement of designed tau-microRNAs to effectively reduce tau pathology, providing a proof of concept for a potential therapeutic approach based on local tau knockdown to rescue tauopathy-related phenotypes.
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MicroRNAs , Tauopatias , Camundongos , Humanos , Animais , Idoso , Proteínas tau/genética , Proteínas tau/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Tauopatias/genética , Tauopatias/terapia , Tauopatias/metabolismo , Neurônios/metabolismo , Fenótipo , Camundongos Transgênicos , Modelos Animais de DoençasRESUMO
BACKGROUND: Up to 30% of patients with Guillain-Barré syndrome require mechanical ventilation and 5% die due to acute complications of mechanical ventilation. There is a considerable group of patients that will need prolonged mechanical ventilation (considered as >14 days) and should be considered for early tracheostomy. The objective of this study is to identify risk factors for prolonged mechanical ventilation. METHODS: We prospectively analyzed patients with Guillain-Barré diagnosis with versus without prolonged mechanical ventilation. We considered clinical and electrophysiological characteristics and analyzed factors associated with prolonged mechanical ventilation. RESULTS: Three hundred and three patients were included; 29% required mechanical ventilation. When comparing the groups, patients with prolonged invasive mechanical ventilation (IMV) have a lower score on the Medical Research Council score (19.5 ± 16.2 vs 27.4 ± 17.5, p = 0.03) and a higher frequency of dysautonomia (42.3% vs 19.4%, p = 0.037), as well as lower amplitudes of the distal compound muscle action potential (CMAP) of the median nerve [0.37 (RIQ 0.07-2.25) vs. 3.9 (RIQ1.2-6.4), p = <0.001] and ulnar nerve [0.37 (RIQ0.0-3.72) vs 1.5 (RIQ0.3-6.6), p = <0.001], and higher frequency of severe axonal damage in these nerves (distal CMAP ≤ 1.0 mV). Through binary logistic regression, severe axonal degeneration of the median nerve is an independent risk factor for prolonged IMV OR 4.9 (95%CI 1.1-21.5) p = 0.03, AUC of 0.774, (95%CI 0.66-0.88), p = < 0.001. CONCLUSIONS: Severe median nerve damage is an independent risk factor for prolonged mechanical ventilation.
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Doenças do Sistema Nervoso Autônomo , Síndrome de Guillain-Barré , Humanos , Síndrome de Guillain-Barré/complicações , Respiração Artificial/efeitos adversos , Modelos Logísticos , Fatores de TempoRESUMO
OBJECTIVE: Reducing maternal morbidity and mortality has been a challenge for low and middle-income countries, especially in the setting of hypertensive disorders of pregnancy. Improved strategies for treating obstetric patients with resistant hypertension are needed. We sought to explore whether hemodynamic parameters may be used to identify patients that develop resistant hypertension in pregnancy. METHODS: Retrospective cohort study among pregnant patients with gestational hypertension or preeclampsia that experienced severe blood pressure elevations. Hemodynamic variables were evaluated, including cardiac output (CO), and total peripheral resistance (TPR). The primary endpoint was resistant hypertension. An exploratory logistic regression was performed to evaluate the association between the hemodynamic profile and the development of resistant hypertension. Adverse maternal and fetal outcomes were additionally described according to the presence of resistant hypertension. RESULTS: Fifty-seven patients with severe pregnancy hypertension were included, of whom 34 developed resistant hypertension (59.7%). The resistant hypertension group, in comparison to those without resistant hypertension, presented with a hypodynamic profile characterized by reduced CO < 5 L/min (41.2% vs. 8.7%, p: 0.007), and increased TPR > 1400 dyn-s/cm5 (64.7% vs. 39.1%, p: 0.057). Logistic regression analysis revealed an association between a hypodynamic profile and resistant hypertension (OR 3.252, 95% CI 1.079-9.804; p = 0.035). Newborns of the resistant hypertension group had more frequent low birth weight (<2500 g), low Apgar scores, ICU admissions, and acute respiratory distress syndrome. CONCLUSION: Patients experiencing hypertensive crisis during pregnancy and exhibiting a hypodynamic profile (TPR ≥1400 dyn·s/cm5 and CO ≤ 5 L/min) developed higher rates of resistant hypertension.
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Hipertensão Induzida pela Gravidez , Crise Hipertensiva , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Recém-Nascido , Estudos Retrospectivos , HemodinâmicaRESUMO
The asymptomatic population's role in COVID-19 transmission poses challenges for control efforts. Pregnant women are susceptible to severe manifestations, increasing maternal and perinatal morbidity and mortality. This study describes the clinical characteristics, maternal and fetal outcomes, and our experience in universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening of pregnant women admitted to a high-complexity obstetric unit in Latin America. Of 568 pregnant women tested for SARS-CoV-2, 23 obtained a positive result. Among these patients, 17% had symptoms at admission, and 0.2% reported an epidemiological link. Pregnant women with positive were associated with an increased risk of eclampsia (16.7% vs 4.9%, P = .014) and acute respiratory distress (16.7% vs 4.9%, P = .014). In this group, 4 patients developed maternal near misses, and no maternal deaths were noted. Two early perinatal deaths occurred in the positive SARS-CoV-2 test group (2, 9.5% vs 17, 4.1%, P = .235). The high prevalence of asymptomatic pregnant women with SARS-CoV-2 and the adverse outcomes for those infected during pregnancy highlights the importance of universal screening upon hospital admission. This approach streamlines risk management, and enhances service structure, resource allocation, care pathways, patient management, follow-up, and overall outcomes.
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BACKGROUND: Recent studies underscore the significance of adopting a syndemics approach to study opioid misuse, overdose, hepatitis C (HCV) and HIV infections, within the broader context of social and environmental contexts in already marginalized communities. Social interactions and spatial contexts are crucial structural factors that remain relatively underexplored. This study examines the intersections of social interactions and spatial contexts around injection drug use. More specifically, we investigate the experiences of different residential groups among young (aged 18-30) people who inject drugs (PWID) regarding their social interactions, travel behaviors, and locations connected to their risk behaviors. By doing so, we aim to achieve a more comprehensive understanding of the multidimensional risk environment, thereby facilitating the development of informed policies. METHODS: We collected and examined data regarding young PWID's egocentric injection network and geographic activity spaces (i.e., where they reside, inject drugs, purchase drugs, and meet sex partners). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multidimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. RESULTS: Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residential group on the West side of Chicago in Illinois where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages. Significant differences were observed in social network structures and travel behaviors: suburban participants had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections, while the urban group had the shortest travel distance for all types of risk activities. CONCLUSION: Distinct residential groups exhibit varying patterns of network interaction, travel behaviors, and geographical contexts related to their risk behaviors. Nonetheless, these groups share common concentrated risk activity spaces in a large outdoor urban drug market area, underscoring the significance of accounting for risk spaces and social networks in addressing syndemics within PWID populations.
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Usuários de Drogas , Infecções por HIV , Hepatite C , Abuso de Substâncias por Via Intravenosa , Humanos , Abuso de Substâncias por Via Intravenosa/epidemiologia , Assunção de Riscos , HepacivirusRESUMO
Soluble secretory proteins with a signal peptide reach the extracellular space through the endoplasmic reticulum-Golgi conventional pathway. During translation, the signal peptide is recognised by the signal recognition particle and results in a co-translational translocation to the endoplasmic reticulum to continue the secretory pathway. However, soluble secretory proteins lacking a signal peptide are also abundant, and several unconventional (endoplasmic reticulum/Golgi independent) pathways have been proposed and some demonstrated. This work describes new features of the secretion signal called Nß, originally identified in NaTrxh, a plant extracellular thioredoxin, that does not possess an orthodox signal peptide. We provide evidence that other proteins, including thioredoxins type h, with similar sequences are also signal peptide-lacking secretory proteins. To be a secretion signal, positions 5, 8 and 9 must contain neutral residues in plant proteins-a negative residue in position 8 is suggested in animal proteins-to maintain the Nß motif negatively charged and a hydrophilic profile. Moreover, our results suggest that the NaTrxh translocation to the endoplasmic reticulum occurs as a post-translational event. Finally, the Nß motif sequence at the N- or C-terminus could be a feature that may help to predict protein localisation, mainly in plant and animal proteins.
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Retículo Endoplasmático , Sinais Direcionadores de Proteínas , Animais , Retículo Endoplasmático/metabolismo , Sequência de Aminoácidos , Transporte Proteico , Complexo de Golgi/metabolismo , PlantasRESUMO
Ten species of Progomphus Selys, 1854 are known to occur in Argentina. The larval stages of only four of them are described. We here add the larval descriptions of two species: P. aberrans Belle, 1973 and P. kimminsi Belle, 1973, and diagnose and illustrate important characters for the remaining species known at the larval stage in Argentina: P. complicatus Selys, 1854, P. joergenseni Ris, 1908, P. lepidus Ris, 1911 and P. phyllochromus Ris, 1918. New geographical records for these species are presented, including new records for P. kimminsi in Bolivia, and new provincial records in Argentina: P. aberrans and P. joergenseni in San Luis, and P. kimminsi in Santiago del Estero. A key to distinguish the larval stage of Argentinean species is proposed.
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Dipterocarpaceae , Odonatos , Animais , Larva , ArgentinaRESUMO
Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.
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Introducción: El objetivo de esta investigación fue confirmar la estructura interna de la Environmental Reward Observation Scale (EROS) y recoger evidencias de su relación con otros constructos en una muestra colombiana de 902 adultos que consintieron participar voluntariamente. Método: Se realizaron análisis psicométricos con Teoría Clásica de los Test y el modelo de Rasch. Se recolectaron evidencias de validez de la estructura interna y de la relación de las puntuaciones con otras variables. Resultados: Se obtuvieron buenos índices en los coeficientes alfa y omega de McDonald, nueve de los 10 ítems tuvieron buenos ajustes en los índices infit y outfit, y el ítem ocho presentó DIF en el nivel educativo. Se confirmó la estructura unidimensional de la EROS y fue invariante respecto al sexo y nivel educativo. Los puntajes tuvieron correlaciones de magnitud alta con sintomatología emocional y variables afines a la Activación Conductual. Conclusiones: La EROS presentó altas calidades psicométricas para su uso en población colombiana; sin embargo, se recomienda su uso solo para evaluación de tamizaje, porque los niveles de información están centrados en un área reducida a lo largo de la métrica logit.
Introduction: The aim of this research was to confirm the internal structure of the Environmental Reward Observation Scale (EROS) and to collect evidence of its relationship with other constructs in a Colombian sample of 902 adults who voluntarily consented to participate. Method: Psychometric analyses were performed using Classical Test Theory and the Rasch model. Evidence of validity based on internal structure and relations of scores with other variables was collected. Results: Good indexes were obtained in McDonald's Alpha and Omega coefficients, 9 of the 10 items had good adjustments in the Infit and Outfit indexes, and item 8 presented DIF in the educational level. The unidimensional structure of the EROS was confirmed and was invariant with respect to sex and educational level. Scores had high magnitude correlations with emotional symptomatology and variables related to Behavioral Activation. Conclusions: The EROS presented high psychometric qualities for its use in the Colombian population; however, its use is recommended only for screening assessment because the levels of information are centered in a reduced area along the Logit scaling.
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BACKGROUND: Pregnant women are at greater risk of adverse outcomes, including mortality, as well as obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear. METHODS: Plasma samples were collected from pregnant women and non-pregnant individuals (male and female) with (n = 72 pregnant, 52 non-pregnant) and without (n = 29 pregnant, 41 non-pregnant) COVID-19. COVID-19 patients were grouped as asymptomatic, mild, moderate, severe, or critically ill according to NIH classifications. Proteomic profiling of 7,288 analytes corresponding to 6,596 unique protein targets was performed using the SOMAmer platform. RESULTS: Herein, we profile the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls and show alterations that display a dose-response relationship with disease severity; yet, such proteomic perturbations are dampened during pregnancy. In both pregnant and non-pregnant state, the proteome response induced by COVID-19 shows enrichment of mediators implicated in cytokine storm, endothelial dysfunction, and angiogenesis. Shared and pregnancy-specific proteomic changes are identified: pregnant women display a tailored response that may protect the conceptus from heightened inflammation, while non-pregnant individuals display a stronger response to repel infection. Furthermore, the plasma proteome can accurately identify COVID-19 patients, even when asymptomatic or with mild symptoms. CONCLUSION: This study represents the most comprehensive characterization of the plasma proteome of pregnant and non-pregnant COVID-19 patients. Our findings emphasize the distinct immune modulation between the non-pregnant and pregnant states, providing insight into the pathogenesis of COVID-19 as well as a potential explanation for the more severe outcomes observed in pregnant women.
Pregnant COVID-19 patients are at increased risk of experiencing complications and severe outcomes compared to the general population. However, the reasons for this heightened risk are still unclear. We measured the proteins present in the blood of pregnant and non-pregnant patients with COVID-19 and compared these to healthy individuals. We found that some COVID-19-associated proteins were present at lower levels in pregnant women, which could help to protect the fetus from harmful inflammation, the body's natural response to infection. While some proteins affected by COVID-19 are shared between pregnant and non-pregnant patients, others were distinctly affected only in pregnant women, providing a potential explanation for the more severe outcomes in this group.
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Background: It is estimated that there are 1.5% US adult population who inject drugs in 2018, with young adults aged 18-39 showing the highest prevalence. PWID are at a high risk of many blood-borne infections. Recent studies have highlight the importance of employing the syndemic approach to study opioid misuse, overdose, HCV and HIV, along with the social and environmental contexts where these interrelated epidemics occur in already marginalized communities. Social interactions and spatial contexts are important structural factors that are understudied. Methods: Egocentric injection network and geographic activity spaces for young (aged 18-30) PWID and their injection, sexual, and social support network members (i.e., where reside, inject drugs, purchase drugs, and meet sex partners) were examined using baseline data from an ongoing longitudinal study (n=258). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multi-dimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. Results: Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residence group on the West side of Chicago where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages (e.g., higher poverty rate, p <0.001). Significant ( p <0.01 for all) differences were observed in social network structures: suburban had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections. Conclusion: We identified concentrated risk activity spaces among PWID from urban, suburban, and transient groups in a large outdoor urban drug market area, which highlights the need for considering the role of risk spaces and social networks in addressing the syndemics in PWID populations.