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1.
Toxicon X ; 23: 100202, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39246647

RESUMEN

The performance of dynamic body-feed filtration (DBF) in the removal of bulky solids produced during the manufacturing of snake antivenoms using the caprylic acid method was evaluated. For this purpose, diatomites with different filterability properties were compared in a bench-scale study to assess their effectiveness in removing the precipitated material formed after the addition of caprylic acid to equine hyperimmune plasma. C1000 diatomite at a concentration of 90 g/L of precipitated plasma showed the best performance. Then, the process was scaled up to three batches of 50 L of hyperimmune horse plasma. At this pilot scale, 108 ± 4% of the immunoglobulins present following plasma precipitation were recovered after DBF. The antivenoms generated using this procedure met quality specifications. When compared to open filtration systems commonly used at an industrial scale by many antivenom manufacturers, DBF has a similar yield and produces filtrates with comparable physicochemical characteristics. However, DBF ensures the microbiological quality of the primary clarification in a way that open systems cannot. This is because: 1) DBF is performed in a single-use closed device of depth filters which prevents microbial contamination, and 2) DBF removes bulky material in few minutes instead of the more than 24 h needed by open filtration systems, thus reducing the risk of contamination. It was concluded that DBF is a cost-effective, easily validated, and GMP-compliant alternative for primary clarification following caprylic acid precipitation of plasma in snake antivenom production.

2.
Environ Res ; 262(Pt 2): 119884, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39243841

RESUMEN

The burgeoning demand for durable and eco-friendly road infrastructure necessitates the exploration of innovative materials and methodologies. This study investigates the potential of Graphene Oxide (GO), a nano-material known for its exceptional dispersibility and mechanical reinforcement capabilities, to enhance the sustainability and durability of concrete pavements. Leveraging the synergy between advanced artificial intelligence techniques-Artificial Neural Networks (ANN), Genetic Algorithms (GA), and Particle Swarm Optimization (PSO)-it is aimed to delve into the intricate effects of Nano-GO on concrete's mechanical properties. The empirical analysis, underpinned by a comparative evaluation of ANN-GA and ANN-PSO models, reveals that the ANN-GA model excels with a minimal forecast error of 2.73%, underscoring its efficacy in capturing the nuanced interactions between GO and cementitious materials. An optimal concentration is identified through meticulous experimentation across varied Nano-GO dosages that amplify concrete's compressive, flexural, and tensile strengths without compromising workability. This optimal dosage enhances the initial strength significantly, and positions GO as a cornerstone for next-generation premium-grade pavement concretes. The findings advocate for the further exploration and eventual integration of GO in road construction projects, aiming to bolster ecological sustainability and propel the adoption of a circular economy in infrastructure development.

3.
Acta Radiol ; : 2841851241278337, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39295291

RESUMEN

BACKGROUND: Rotational abnormalities of the hip have been implicated in the etiology of diseases, such as hip dysplasia, osteoarthritis, and femoroacetabular impingement. Despite the extensive literature on hip morphology, there is a gap in knowledge regarding variations in the Hispanic population. PURPOSE: To describe the bony anatomy variations of the acetabulum in a Hispanic population. MATERIAL AND METHODS: This is a cross-sectional study. We studied 182 computed tomography (CT) images in patients aged older than 21 years, who had undergone pelvic CT for any condition, except hip fracture. Measurements of acetabular version, anterior and posterior acetabular sector angles (AASA/PASA) and horizontal acetabular sector angles (HASA) were made. Acetabular variations were then compared to weight and sex data. RESULTS: The mean acetabular anteversion was greater in women (P < 0.001). Women exhibited a greater PASA (P < 0.05); however, men had a greater AASA (P < 0.05). Underweight individuals had a smaller PASA (P < 0.01) and HASA (P < 0.05) than individuals with a normal weight. CONCLUSION: The Hispanic hip is morphologically similar to other populations previously reported in the literature; however, Hispanic men have less coverage of the femoral head by the posterior acetabular wall when compared to women of the same ethnicity. These abnormalities have a direct impact on management and surgical approach in patients treated for femoroacetabular impingement and hip dysplasia.

4.
Toxicon X ; 24: 100206, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39290878

RESUMEN

Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and in vitro procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.

5.
Artículo en Inglés | MEDLINE | ID: mdl-39088847

RESUMEN

Snakebite envenoming kills and maims hundreds of thousands of people every year, especially in the rural settings of tropical regions. Envenomings are still treated with animal-derived antivenoms, which have prevented many lives from being lost but which are also medicines in need of innovation. Strides are being made to improve envenoming therapies, with promising efforts made toward optimizing manufacturing and quality aspects of existing antivenoms, accelerating research and development of recombinant antivenoms based on monoclonal antibodies, and repurposing of small-molecule inhibitors that block key toxins. Here, we review the most recent advances in these fields and discuss therapeutic opportunities and limitations for different snakebite treatment modalities. Finally, we discuss challenges related to preclinical and clinical evaluation, regulatory pathways, large-scale manufacture, and distribution and access that need to be addressed to fulfill the goals of the World Health Organization's global strategy to prevent and control snakebite envenoming.

6.
Am J Trop Med Hyg ; 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39106853

RESUMEN

In an open randomized controlled trial, we compared one vial (10 mL) to two vials (20 mL) of EchiTAb-plus-ICP (EPI) antivenom among children with systemic carpet viper (Echis romani) envenoming of moderate severity in northeastern Nigeria. Systemic envenoming, presenting with incoagulable blood, was diagnosed using the 20-minute whole blood clotting test (20WBCT). Eligible patients with positive 20WBCT whose guardians assented were recruited and randomly allocated to receive either one vial or two vials of EPI administered either as a bolus or as a slow continuous infusion. The primary outcome was permanent restoration of blood coagulability 6 hours after the start of treatment, assessed by the 20WBCT and repeated at 6, 12, 24, and 48 hours after treatment. Secondary outcomes were the incidences of early adverse reactions to antivenom treatment. Initial doses permanently restored blood coagulability at 6 hours in 34/39 (87.2%) of those treated with one vial and 39/41 (95.1%) of those treated with two vials of EPI (P = 0.258). However, the proportion with permanent restoration of clotting at 6 hours among patients randomized to bolus administration was 41 of 42 (97.6%) patients compared with 32 of 38 (84.2%) patients randomized to slow infusion of EPI antivenom (P = 0.049); however, the difference was not sustained through the remaining time points. There was no difference in early adverse reactions between those treated with the two different doses or modes of delivery. We conclude that the one-vial dose compared favorably to two vials of EPI antivenom with regards to effectiveness and safety among children with carpet viper envenoming of moderate severity in Nigeria.

7.
bioRxiv ; 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39185220

RESUMEN

Cardiovascular disease (CVD) is associated with both genetic variants and environmental factors. One unifying consequence of the molecular risk factors in CVD is DNA damage, which must be repaired by DNA damage response proteins. However, the impact of DNA damage on global cardiomyocyte protein abundance, and its relationship to CVD risk remains unclear. We therefore treated induced pluripotent stem cell-derived cardiomyocytes with the DNA-damaging agent Doxorubicin (DOX) and a vehicle control, and identified 4,178 proteins that contribute to a network comprising 12 co-expressed modules and 403 hub proteins with high intramodular connectivity. Five modules correlate with DOX and represent distinct biological processes including RNA processing, chromatin regulation and metabolism. DOX-correlated hub proteins are depleted for proteins that vary in expression across individuals due to genetic variation but are enriched for proteins encoded by loss-of-function intolerant genes. While proteins associated with genetic risk for CVD, such as arrhythmia are enriched in specific DOX-correlated modules, DOX-correlated hub proteins are not enriched for known CVD risk proteins. Instead, they are enriched among proteins that physically interact with CVD risk proteins. Our data demonstrate that DNA damage in cardiomyocytes induces diverse effects on biological processes through protein co-expression modules that are relevant for CVD, and that the level of protein connectivity in DNA damage-associated modules influences the tolerance to genetic variation.

9.
Ann N Y Acad Sci ; 1538(1): 144-161, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39086254

RESUMEN

This study analyzes the relationship between drought processes and crop yields in Moldova, together with the effects of possible future climate change on crops. The severity of drought is analyzed over time in Moldova using the Standard Precipitation Index, the Standardized Precipitation Evapotranspiration Index, and their relationship with crop yields. In addition, rainfall variability and its relationship with crop yields are examined using spectral analysis and squared wavelet coherence. Observed station data (1950-2020 and 1850-2020), ERA5 reanalysis data (1950-2020), and climate model simulations (period 1970-2100) are used. Crop yield data (maize, sunflower, grape), data from experimental plots (wheat), and the Enhanced Vegetation Index from Moderate Resolution Imaging Spectroradiometer satellites were also used. Results show that although the severity of meteorological droughts has decreased in the last 170 years, the impact of precipitation deficits on different crop yields has increased, concurrent with a sharp increase in temperature, which negatively affected crop yields. Annual crops are now more vulnerable to natural rainfall variability and, in years characterized by rainfall deficits, the possibility of reductions in crop yield increases due to sharp increases in temperature. Projections reveal a pessimistic outlook in the absence of adaptation, highlighting the urgency of developing new agricultural management strategies.


Asunto(s)
Productos Agrícolas , Sequías , Calentamiento Global , Productos Agrícolas/crecimiento & desarrollo , Moldavia , Adaptación Fisiológica/fisiología , Cambio Climático , Lluvia , Modelos Climáticos , Zea mays/crecimiento & desarrollo , Zea mays/fisiología , Triticum/crecimiento & desarrollo , Triticum/fisiología , Temperatura
10.
AIDS Res Ther ; 21(1): 57, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39187870

RESUMEN

Chronic viral infections caused by the human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common among patients with end-stage renal disease (ESKD). These infections were once considered contraindications to kidney transplantation due to potential risks associated with long-term immunosuppression. Improved management and antiviral therapies have changed the prognosis and survival of this group of patients, along with an increased experience in transplanting people with these viral infections. We report the first successful kidney transplant in an ESKD patient on hemodialysis with a history of concomitant HIV, HCV and HBV infection in Mexico.


Asunto(s)
Infecciones por VIH , Fallo Renal Crónico , Trasplante de Riñón , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/complicaciones , Masculino , Hepatitis B/complicaciones , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , México , Persona de Mediana Edad , Adulto , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Resultado del Tratamiento , Diálisis Renal
11.
ACS Omega ; 9(31): 34089-34097, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39130572

RESUMEN

To maintain economic profitability and stabilize fuel prices, refineries actively explore alternatives for efficiently processing (extra) heavy crude oils. These oils are challenging to process due to their complex composition, which includes significant quantities of asphaltenes, resins, and sulfur and nitrogen heteroatoms. A critical initial step in upgrading these oils is the hydrogenation of polyaromatic compounds, requiring substantial hydrogen sources. Methane from natural gas streams is known to act as an effective hydrogen donor. This study investigates the use of a heteropolyacid (HPA) catalyst modified with nickel and methane to enhance the quality of heavy crude oil with an initial 8.0°API (at 15.5 °C) and 2200 cSt viscosity (at 37.5 °C). After treatment in a batch reactor at 380 °C and 4.4 MPa for 2 h, the oil properties markedly improved: API gravity increased from 8.0 to 16.0 (at 15.5 °C), and kinematic viscosity reduced from 2200 to 125 cSt (at 37.5 °C). Additionally, there was a significant decrease in asphaltenes (from 38.7 to 16.4% by weight), sulfur (from 5.9 to 4.0% by weight), and nitrogen (from 971 to 695 ppm). This was accompanied by an increase in the volume of light distillates from 1.3 to 4.9%, and middle distillates from 8.8 to 21.0%. These results suggest that nickel-modified HPA catalysts, combined with methane as a hydrogen donor, are a promising option for upgrading heavy crude oils.

12.
Nefrologia (Engl Ed) ; 44(4): 475-485, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39127583

RESUMEN

The multidimensional view of disease is fundamental in the care of complex diseases such as chronic kidney disease (CKD). It is appropriate to define and unify concepts that allow the different professionals involved in care to provide a multidisciplinary approach tailored to the needs of each individual. Given the increasing incidence of CKD worldwide and the fact that the disease may progress at different rates, there is a need to establish personalized, comprehensive approaches for each patient and their families at an earlier stage. This approach goes beyond the simple control of uremic symptoms or congestion and consists of addressing not only symptomatic but also functional, social and coping problems at an early stage, facilitating decision making both in the CKD and in acute situations, potentially irreversible or interventions that do not improve life expectancy. To ensure excellence in care, it is important to assess indicators of palliative care and kidney support, such as the presence of advance and shared care planning, the inclusion of psychosocial, ethical, spiritual and bereavement care. This enables the provision of comprehensive, humanized, and high-quality care for patients and their families. Palliative and kidney care is not just about patients in the last days of life. Defining, unifying, and evaluating the concepts will allow them to be applied in a timely manner at each specific moment of the CKD trajectory.


Asunto(s)
Cuidados Paliativos , Cuidado Terminal , Terminología como Asunto , Humanos , Cuidado Terminal/normas , Insuficiencia Renal Crónica/terapia , Planificación Anticipada de Atención
13.
bioRxiv ; 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39211276

RESUMEN

OBJECTIVE: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. METHODS: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. RESULTS: We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. CONCLUSIONS: Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

14.
Fungal Genet Biol ; 174: 103914, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032808

RESUMEN

Lignocellulosic material is a leading carbon source for economically viable biotechnological processes; however, compounds such furfural and acetic acid exhibit toxicity to yeasts. Nonetheless, research about the molecular mechanism of furfural and acetic acid toxicity is still scarce in yeasts like Scheffersomyces stipitis. Thus, this study aims to elucidate the impact of furfural and acetic acid on S. stipitis regarding bioenergetic and fermentation parameters. Here, we provide evidence that furfural and acetic acid induce a delay in cell growth and extend the lag phase. The mitochondrial membrane potential decreased in all treatments with no significant differences between inhibitors or concentrations. Interestingly, reactive oxygen species increased when the inhibitor concentrations were from 0.1 to 0.3 % (v/v). The glycolytic flux was not significantly (p > 0.05) altered by acetic acid, but furfural caused different effects. Ethanol production decreased significantly (4.32 g·L-1 in furfural and 5.06 g·L-1 in acetic acid) compared to the control (26.3 g·L-1). In contrast, biomass levels were not significantly different in most treatments compared to the control. This study enhances our understanding of the effects of furfural and acetic acid at the mitochondrial level in a pentose-fermenting yeast like S. stipitis.


Asunto(s)
Ácido Acético , Metabolismo Energético , Fermentación , Furaldehído , Saccharomycetales , Furaldehído/farmacología , Furaldehído/metabolismo , Ácido Acético/farmacología , Ácido Acético/metabolismo , Metabolismo Energético/efectos de los fármacos , Saccharomycetales/metabolismo , Saccharomycetales/efectos de los fármacos , Saccharomycetales/crecimiento & desarrollo , Etanol/metabolismo , Etanol/farmacología , Especies Reactivas de Oxígeno/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Lignina/metabolismo , Biomasa , Glucólisis/efectos de los fármacos
15.
Biol Res ; 57(1): 49, 2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39068496

RESUMEN

BACKGROUND: The significant role of embryonic cerebrospinal fluid (eCSF) in the initial stages of brain development has been thoroughly studied. This fluid contains crucial molecules for proper brain development such as members of the Wnt and FGF families, apolipoproteins, and retinol binding protein. Nevertheless, the source of these molecules remains uncertain since they are present before the formation of the choroid plexus, which is conventionally known as the primary producer of cerebrospinal fluid. The subcommissural organ (SCO) is a highly conserved gland located in the diencephalon and is one of the earliest differentiating brain structures. The SCO secretes molecules into the eCSF, prior to the differentiation of the choroid plexus, playing a pivotal role in the homeostasis and dynamics of this fluid. One of the key molecules secreted by the SCO is SCO-spondin, a protein involved in maintenance of the normal ventricle size, straight spinal axis, neurogenesis, and axonal guidance. Furthermore, SCO secretes transthyretin and basic fibroblast growth factor 2, while other identified molecules in the eCSF could potentially be secreted by the SCO. Additionally, various transcription factors have been identified in the SCO. However, the precise mechanisms involved in the early SCO development are not fully understood. RESULTS: To uncover key molecular players and signaling pathways involved in the role of the SCO during brain development, we conducted a transcriptomic analysis comparing the embryonic chick SCO at HH23 and HH30 stages (4 and 7 days respectively). Additionally, a public transcriptomic data from HH30 entire chick brain was used to compare expression levels between SCO and whole brain transcriptome. These analyses revealed that, at both stages, the SCO differentially expresses several members of bone morphogenic proteins, Wnt and fibroblast growth factors families, diverse proteins involved in axonal guidance, neurogenic and differentiative molecules, cell receptors and transcription factors. The secretory pathway is particularly upregulated at stage HH30 while the proliferative pathway is increased at stage HH23. CONCLUSION: The results suggest that the SCO has the capacity to secrete several morphogenic molecules to the eCSF prior to the development of other structures, such as the choroid plexus.


Asunto(s)
Encéfalo , Perfilación de la Expresión Génica , Órgano Subcomisural , Animales , Encéfalo/metabolismo , Encéfalo/embriología , Encéfalo/crecimiento & desarrollo , Órgano Subcomisural/metabolismo , Órgano Subcomisural/embriología , Embrión de Pollo , Regulación del Desarrollo de la Expresión Génica
16.
J Am Heart Assoc ; 13(15): e035691, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39023069

RESUMEN

BACKGROUND: Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging. METHODS AND RESULTS: We included 1257 participants from the NOMAS (Northern Manhattan Study). The ePWV values were calculated using a nonlinear function of age and mean arterial blood pressure. The association between ePWV and white matter hyperintensity volume was assessed. Modification by race and ethnicity was evaluated. Associations between ePWV and other cerebral small-vessel disease markers, covert brain infarcts, cerebral microbleeds, and enlarged perivascular spaces, were explored as secondary outcomes. Mean±SD age of the cohort was 64±8 years; 61% were women; 18% self-identified as non-Hispanic Black, 67% as Hispanic, and 15% as non-Hispanic White individuals. Mean±SD ePWV was 11±2 m/s in the total NOMAS population and was similar across race and ethnic groups. The ePWV was significantly associated with white matter hyperintensity volume (ß=0.23 [95% CI, 0.20-0.26]) after adjustment. Race and ethnicity modified the association between ePWV and white matter hyperintensity volume, with stronger associations in Hispanic and non-Hispanic Black individuals. Significant associations were found between ePWV and covert brain infarcts, cerebral microbleeds, and perivascular spaces after adjustment. CONCLUSIONS: The ePWV function may provide a vascular mechanism for deleterious cerebrovascular outcomes in individuals with cerebral small-vessel disease and is particularly apparent in the racial and ethnic minorities represented in the NOMAS cohort.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Imagen por Resonancia Magnética , Análisis de la Onda del Pulso , Rigidez Vascular , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedades de los Pequeños Vasos Cerebrales/fisiopatología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico por imagen , Enfermedades de los Pequeños Vasos Cerebrales/etnología , Anciano , Rigidez Vascular/fisiología , Ciudad de Nueva York/epidemiología , Factores de Riesgo , Negro o Afroamericano , Valor Predictivo de las Pruebas , Hispánicos o Latinos/estadística & datos numéricos , Población Blanca
17.
Environ Res ; 260: 119526, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-38972341

RESUMEN

Rainwater Harvesting (RWH) is increasingly recognized as a vital sustainable practice in urban environments, aimed at enhancing water conservation and reducing energy consumption. This study introduces an innovative integration of nano-composite materials as Silver Nanoparticles (AgNPs) into RWH systems to elevate water treatment efficiency and assess the resulting environmental and energy-saving benefits. Utilizing a regression analysis approach with Support Vector Machines (SVM) and K-Nearest Neighbors (KNN), this study will reach the study objective. In this study, the inputs are building attributes, environmental parameters, sociodemographic factors, and the algorithms SVM and KNN. At the same time, the outputs are predicted energy consumption, visual comfort outcomes, ROC-AUC values, and Kappa Indices. The integration of AgNPs into RWH systems demonstrated substantial environmental and operational benefits, achieving a 57% reduction in microbial content and 20% reductions in both chemical usage and energy consumption. These improvements highlight the potential of AgNPs to enhance water safety and reduce the environmental impact of traditional water treatments, making them a viable alternative for sustainable water management. Additionally, the use of a hybrid SVM-KNN model effectively predicted building energy usage and visual comfort, with high accuracy and precision, underscoring its utility in optimizing urban building environments for sustainability and comfort.


Asunto(s)
Aprendizaje Automático , Plata , Ciudades , Purificación del Agua/métodos , Nanopartículas del Metal , Lluvia , Conservación de los Recursos Hídricos/métodos , Máquina de Vectores de Soporte
18.
Sci Transl Med ; 16(756): eadk4802, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39018365

RESUMEN

Snakebites affect about 1.8 million people annually. The current standard of care involves antibody-based antivenoms, which can be difficult to access and are generally not effective against local tissue injury, the primary cause of morbidity. Here, we used a pooled whole-genome CRISPR knockout screen to define human genes that, when targeted, modify cell responses to spitting cobra venoms. A large portion of modifying genes that conferred resistance to venom cytotoxicity was found to control proteoglycan biosynthesis, including EXT1, B4GALT7, EXT2, EXTL3, XYLT2, NDST1, and SLC35B2, which we validated independently. This finding suggested heparinoids as possible inhibitors. Heparinoids prevented venom cytotoxicity through binding to three-finger cytotoxins, and the US Food and Drug Administration-approved heparinoid tinzaparin was found to reduce tissue damage in mice when given via a medically relevant route and dose. Overall, our systematic molecular dissection of cobra venom cytotoxicity provides insight into how we can better treat cobra snakebite envenoming.


Asunto(s)
Venenos Elapídicos , Mordeduras de Serpientes , Animales , Humanos , Mordeduras de Serpientes/tratamiento farmacológico , Ratones , Antídotos/farmacología
19.
Toxins (Basel) ; 16(7)2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-39057931

RESUMEN

This study investigated the intraspecific and interspecific variability in the venom effects of Agkistrodon viperid snake species and subspecies (eleven venoms total) on plasma clotting times, fibrinogen levels, and fibrin clot strength. Significant delays in plasma clotting time were observed for A. conanti, A. contortrix mokasen, A. contortrix phaeogaster, A. howardgloydi, A. piscivorus leucostoma, and A. piscivorus piscivorus. Notably, the phylogenetically disjunct lineages A. conanti, A. contortrix mokasen, and A. howardgloydi exhibited the most potent anticoagulant effects, indicating the independent amplification of a basal trait. Inhibition assays with the activated clotting enzymes Factors XIa, IXa, Xa, and IIa (thrombin) revealed that FXa inhibition is another basal trait amplified independently on multiple occasions within the genus, but with A. howardgloydi, notably more potent than all others. Phospholipid degradation and zymogen destruction were identified as mechanisms underlying the variability in venom effects observed experimentally and in previous clinical reports. Thromboelastography demonstrated that the venoms did not clot fibrinogen directly but affected fibrin clot strength by damaging fibrinogen and that thrombin was subsequently only able to cleave into weak, unstable clots. The ability to activate Protein C, an endogenous anticoagulant enzyme, varied across species, with some venoms exceeding that of A. contortrix contortrix, which previously yielded the protein diagnostic agent Protac®. Phylogenetic analysis suggested that both fibrinogen degradation and Protein C activation were each amplified multiple times within the genus, albeit with negative correlation between these two modes of action. This study highlights the evolutionary, clinical, and biodiscovery implications of venom variability in the Agkistrodon species, underscoring their dynamic evolution, emphasising the need for tailored clinical approaches, and highlighting the potential for novel diagnostic and therapeutic developments inspired by the unique properties of snake venoms.


Asunto(s)
Agkistrodon , Anticoagulantes , Coagulación Sanguínea , Venenos de Crotálidos , Especificidad de la Especie , Anticoagulantes/farmacología , Animales , Coagulación Sanguínea/efectos de los fármacos , Humanos , Fibrinógeno/metabolismo , Filogenia , Tromboelastografía
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