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1.
PeerJ Comput Sci ; 10: e2095, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38855217

RESUMO

Mixed integer nonlinear programming (MINLP) addresses optimization problems that involve continuous and discrete/integer decision variables, as well as nonlinear functions. These problems often exhibit multiple discontinuous feasible parts due to the presence of integer variables. Discontinuous feasible parts can be analyzed as subproblems, some of which may be highly constrained. This significantly impacts the performance of evolutionary algorithms (EAs), whose operators are generally insensitive to constraints, leading to the generation of numerous infeasible solutions. In this article, a variant of the differential evolution algorithm (DE) with a gradient-based repair method for MINLP problems (G-DEmi) is proposed. The aim of the repair method is to fix promising infeasible solutions in different subproblems using the gradient information of the constraint set. Extensive experiments were conducted to evaluate the performance of G-DEmi on a set of MINLP benchmark problems and a real-world case. The results demonstrated that G-DEmi outperformed several state-of-the-art algorithms. Notably, G-DEmi did not require novel improvement strategies in the variation operators to promote diversity; instead, an effective exploration within each subproblem is under consideration. Furthermore, the gradient-based repair method was successfully extended to other DE variants, emphasizing its capacity in a more general context.

2.
Int J Environ Health Res ; : 1-12, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842028

RESUMO

Various exogenous factors, such as microbiological and chemical contamination condition food security. Salmonella Typhimurium (S. Typhimurium) is the cause of salmonellosis. This bacterium utilizes phagocytosis to create bacterial reservoirs. On the other hand, exposure to chemical contaminants, such as pesticides, increases susceptibility to numerous infections. Therefore, this research aims to evaluate the effect of co-exposure to diazoxon and S. Typhimurium on the in vitro infection dynamics. For this purpose, human mononuclear cells were pre-exposed in vitro to diazoxon and then challenged with S. Typhimurium at 1, 8, and 24 h. Bacterial internalization, actin polymerization, and reactive oxygen species (ROS) were analyzed. Obtained data show that mononuclear cells previously exposed to diazoxon exhibit greater internalization of S. Typhimurium. Likewise, greater ROS production and an increase in actin polymerization were observed. Therefore, in the proposed scenario, obtained data suggest that co-exposure to diazoxon and S. Typhimurium increases susceptibility to acquiring an illness.

3.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38851565

RESUMO

INTRODUCTION: The incidence of hip fracture in the elderly is on the rise, occasionally accompanied by concurrent upper limb fractures. Our investigation aims to determine whether these patients experience poorer functional outcomes, prolonged hospitalization, or higher mortality rates when compared to those with isolated hip fracture. MATERIAL AND METHODS: We retrospectively reviewed 1088 elderly patients admitted to our centre with hip fracture between January 2017 and March 2020. We recorded the presence of concomitant fractures and their treatment. We analyzed the duration of hospital stay, in-hospital mortality and function. RESULTS: We identified 63 patients with concomitant upper limb fracture (5.6%). Among them, 93.7% were women, and the average age was 86.4 years. 80.9% of the upper limb fractures were distal radius or proximal humerus. Patients with concomitant fracture had increased length of stay (mean, 19.6 vs 12.8, p=0.002), decreased proportion of patients returning to their own home at discharge (23.6% vs 26.3%, p=0.042) and increased in-hospital mortality rate (9.5% vs 5.9%, p=0.003). CONCLUSIONS: Patients with concomitant upper limb fracture require a longer length of stay and exhibit an elevated in-hospital mortality rate. Furthermore, this condition is associated with a reduced short-term functional recovery, thereby decreasing the chances of the patient returning home upon hospital discharge.

4.
Front Med (Lausanne) ; 11: 1395698, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933107

RESUMO

Despite important progress in modern medicine, widely regarded as an indispensable foundation of healthcare in all highly advanced nations and regions, not all patients respond well to available treatments in biomedicine alone. Additionally, there are concerns about side effects of many medications and interventions, the unsustainable cost of healthcare and the low resolution of chronic non-communicable diseases and mental disorders whose incidence has risen in the last decades. Besides, the chronic stress and burnout of many healthcare professionals impairs the therapeutic relationship. These circumstances call for a change in the current paradigm and practices of biomedicine healthcare. Most of the world population (80%) uses some form of traditional, complementary, and integrative medicine (T&CM), usually alongside biomedicine. Patients seem equally satisfied with biomedicine and T&CM, but in the field of T&CM there are also many challenges, such as unsupported claims for safety and/or efficacy, contamination of herbal medicines and problems with regulation and quality standards. As biomedicine and T&CM seem to have different strengths and weaknesses, integration of both approaches may be beneficial. Indeed, WHO has repeatedly called upon member states to work on the integration of T&CM into healthcare systems. Integrative medicine (IM) is an approach that offers a paradigm for doing so. It combines the best of both worlds (biomedicine and T&CM), based on evidence for efficacy and safety, adopting a holistic personalized approach, focused on health. In the last decades academic health centers are increasingly supportive of IM, as evidenced by the foundation of national academic consortia for integrative medicine in Brazil (2017), the Netherlands (2018), and Germany (2024) besides the pioneering American consortium (1998). However, the integration process is slow and sometimes met with criticism and even hostility. The WHO T&CM strategies (2002-2005 and 2014-2023) have provided incipient guidance on the integration process, but several challenges are yet to be addressed. This policy review proposes several possible solutions, including the establishment of a global matrix of academic consortia for IM, to update and extend the WHO T&CM strategy, that is currently under review.

5.
J Phys Chem Lett ; 15(21): 5747-5753, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38775633

RESUMO

The use of electric fields applied across magnetic heterojunctions that lack spatial inversion symmetry has been previously proposed as a nonmagnetic means of controlling localized magnetic moments through spin-orbit torques (SOT). The implementation of this concept at the single-molecule level has remained a challenge, however. Here, we present first-principles calculations of SOT in a single-molecule junction under bias and beyond linear response. Employing a self-consistency scheme invoking density functional theory and nonequilibrium Green's function theory including spin-orbit interaction, we compute the change of the magnetization with the bias voltage and the associated current-induced SOT. Within the linear regime our quantitative estimates for the SOT in single-molecule junctions yield values similar to those known for magnetic interfaces. Our findings contribute to an improved microscopic understanding of SOT in single molecules.

6.
Artigo em Inglês | MEDLINE | ID: mdl-38814543

RESUMO

PURPOSE: Determine if the gene expression profiles of ovarian support cells (OSCs) and cumulus-free oocytes are bidirectionally influenced by co-culture during in vitro maturation (IVM). METHODS: Fertility patients aged 25 to 45 years old undergoing conventional ovarian stimulation donated denuded immature oocytes for research. Oocytes were randomly allocated to either OSC-IVM culture (intervention) or Media-IVM culture (control) for 24-28 h. The OSC-IVM culture condition was composed of 100,000 OSCs in suspension culture with human chorionic gonadotropin (hCG), recombinant follicle stimulating hormone (rFSH), androstenedione, and doxycycline supplementation. The Media-IVM control lacked OSCs and contained the same supplementation. A limited set of in vivo matured MII oocytes were donated for comparative evaluation. Endpoints consisted of MII formation rate, morphological and spindle quality assessment, and gene expression analysis compared to in vitro and in vivo controls. RESULTS: OSC-IVM resulted in a statistically significant improvement in MII formation rate compared to the Media-IVM control, with no apparent effect on morphology or spindle assembly. OSC-IVM MII oocytes displayed a closer transcriptomic maturity signature to IVF-MII controls than Media-IVM control MII oocytes. The gene expression profile of OSCs was modulated in the presence of oocytes, displaying culture- and time-dependent differential gene expression during IVM. CONCLUSION: The OSC-IVM platform is a novel tool for rescue maturation of human oocytes, yielding oocytes with improved nuclear maturation and a closer transcriptomic resemblance to in vivo matured oocytes, indicating a potential enhancement in oocyte cytoplasmic maturation. These improvements on oocyte quality after OSC-IVM are possibly occurring through bidirectional crosstalk of cumulus-free oocytes and ovarian support cells.

7.
Hum Vaccin Immunother ; 20(1): 2347019, 2024 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-38807261

RESUMO

Influenza A viruses pose a significant threat to global health, impacting both humans and animals. Zoonotic transmission, particularly from swine and avian species, is the primary source of human influenza outbreaks. Notably, avian influenza viruses of the H5N1, H7N9, and H9N2 subtypes are of pandemic concern through their global spread and sporadic human infections. Preventing and controlling these viruses is critical due to their high threat level. Vaccination remains the most effective strategy for influenza prevention and control in humans, despite varying vaccine efficacy across strains. This review focuses specifically on pandemic preparedness for avian influenza viruses. We delve into vaccines tested in animal models and summarize clinical trials conducted on H5N1, H7N9, and H9N2 vaccines in humans.


Assuntos
Aves , Vacinas contra Influenza , Influenza Aviária , Influenza Humana , Pandemias , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Humanos , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Influenza Humana/imunologia , Influenza Aviária/prevenção & controle , Influenza Aviária/epidemiologia , Pandemias/prevenção & controle , Desenvolvimento de Vacinas , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vírus da Influenza A Subtipo H9N2/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Ensaios Clínicos como Assunto , Modelos Animais de Doenças , Vacinação , Preparação para Pandemia
8.
Int J Inj Contr Saf Promot ; : 1-20, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647115

RESUMO

As the elderly population grows, there is a greater concern for their safety on the roads. This is particularly important for elderly pedestrians who are more vulnerable to accidents. In Spain, one of the most aged countries in the world, the elderly accounted for 70% of all pedestrian deaths in 2019. In this study, the focus was on analysing the occurrence of elderly pedestrian-vehicle collisions in Spanish municipalities and how it is related to the built environment. The study used the hurdle negative binomial model to analyse the number of elderly and non-elderly pedestrian accidents per municipality in 2016-2019. The exploratory analysis showed that cities above 50,000 inhabitants were safer for the elderly, and larger provincial capitals had lower elderly pedestrian traffic accident rates. The occurrence of all pedestrian traffic accidents was linked to the socio-demographic features. For elderly pedestrians, land use was found to be influential, with a lower proportion of land covered by manufacturing and service activities linked to a smaller number of accidents. Results showed that improving road safety for older pedestrians may not necessarily compromise the situation for the rest of population. Hence, policymakers should focus on infrastructure improvements adapted to the needs of elderly pedestrians.

9.
Med Clin (Barc) ; 2024 Apr 19.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38643026

RESUMO

INTRODUCTION: Peripheral arterial disease is a marker of vascular damage that is diagnosed by measuring the ankle-brachial index. The aim of this study was to determine the validity and agreement of the MESI ABPI-MD and Microlife WatchBP® office-ABI oscillometric devices with respect to the gold standard arterial Doppler. MATERIALS AND METHODS: Observational, cross-sectional, descriptive study of inpatients who underwent ABI measurement with the three devices. Values are considered normal between 1-1.4, indeterminate between 0.91-0.99 and pathological ≤0.9 and >1.4. RESULTS: A total of 187 patients (54.4% male) with a mean age of 66 years were included. The Doppler results were inferior to those of the oscillometric devices (median [IQR] 1.1 [0.2] vs. 1.2 [0.2], P<.05), with no significant differences between the automated devices (P=.29 for the right lower limb and P=.342 for the left lower limb). Both devices had high specificity (96.5-99.2%) and low sensitivity (29.5-45.4%). The correlation of the results was good-moderate for MESI and moderate for Microlife. The agreement between the two was acceptable-moderate. CONCLUSION: Automated oscillometric devices could be useful in asymptomatic patients as an alternative to arterial Doppler.

10.
PLoS One ; 19(4): e0302031, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38603692

RESUMO

Chronic neuroinflammation is characterized by increased blood-brain barrier (BBB) permeability, leading to molecular changes in the central nervous system that can be explored with biomarkers of active neuroinflammatory processes. Magnetic resonance imaging (MRI) has contributed to detecting lesions and permeability of the BBB. Ultra-small superparamagnetic particles of iron oxide (USPIO) are used as contrast agents to improve MRI observations. Therefore, we validate the interaction of peptide-88 with laminin, vectorized on USPIO, to explore BBB molecular alterations occurring during neuroinflammation as a potential tool for use in MRI. The specific labeling of NPS-P88 was verified in endothelial cells (hCMEC/D3) and astrocytes (T98G) under inflammation induced by interleukin 1ß (IL-1ß) for 3 and 24 hours. IL-1ß for 3 hours in hCMEC/D3 cells increased their co-localization with NPS-P88, compared with controls. At 24 hours, no significant differences were observed between groups. In T98G cells, NPS-P88 showed similar nonspecific labeling among treatments. These results indicate that NPS-P88 has a higher affinity towards brain endothelial cells than astrocytes under inflammation. This affinity decreases over time with reduced laminin expression. In vivo results suggest that following a 30-minute post-injection, there is an increased presence of NPS-P88 in the blood and brain, diminishing over time. Lastly, EAE animals displayed a significant accumulation of NPS-P88 in MRI, primarily in the cortex, attributed to inflammation and disruption of the BBB. Altogether, these results revealed NPS-P88 as a biomarker to evaluate changes in the BBB due to neuroinflammation by MRI in biological models targeting laminin.


Assuntos
Barreira Hematoencefálica , Laminina , Animais , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/metabolismo , Laminina/metabolismo , Doenças Neuroinflamatórias , Células Endoteliais/metabolismo , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Imageamento por Ressonância Magnética/métodos
11.
J Virol ; 98(5): e0054924, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38624241

RESUMO

As an Argentine scientist, the defunding of CONICET and INTA feels like a blow to progress and our future. Despite free education, these cuts force talented researchers to seek opportunities abroad. Argentina's history of scientific achievement, from Nobel Prizes to COVID-19 vaccines, is at risk. Defunding science weakens our ability to solve problems and compete globally.


Assuntos
Pesquisa Biomédica , Humanos , Argentina , Pesquisa Biomédica/economia , Pesquisa Biomédica/educação , Ciência/economia , Ciência/educação , Fuga de Cérebros
13.
Methods Cell Biol ; 184: 97-103, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38555161

RESUMO

Current strategies to undermine the deleterious influence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment (TME) are lacking effective clinical solutions, in large part, due to insufficient knowledge on susceptible cellular and molecular targets. We describe here the application of biomimetic microfabricated platforms designed to analyze migratory phenotypes of MDSCs in the tumor niche ex vivo, which may enable accelerated therapeutic discovery. By mimicking the guided structural cues present in the physiological architecture of the TME, aligned microtopography substrates can elucidate potential interventions on migratory phenotypes of MDSCs at the single clonal level. Coupled with cellular and molecular biology analysis tools, our approach employs real-time tracking analysis of cell motility to probe the dissemination characteristics of MDSCs under guided migration conditions. These methods allow us to identify cellular subpopulations of interest based on their disseminative and suppressive capabilities. By doing so, we illustrate the potential of applying microscale engineering tools, in concert with dynamic live cell imaging and bioanalysis methods to uncover novel exploitable motility targets for advancing cancer therapy discovery. The inherent simplicity and extended application to a variety of contexts in tumor-associated cell migration render this method widely accessible to existing biological laboratory conditions and interests.


Assuntos
Células Supressoras Mieloides , Neoplasias , Humanos , Células Supressoras Mieloides/patologia , Biomimética , Neoplasias/patologia , Fenótipo , Microambiente Tumoral
14.
Eur J Orthop Surg Traumatol ; 34(4): 1851-1863, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38431896

RESUMO

INTRODUCTION: The purposes of this study were to analyze and compare the functional outcomes and radiological changes around the press-fit humeral components in two contemporary medialized reverse total shoulder arthroplasty (RTSA) systems at a minimum of 5-year follow-up. MATERIALS AND METHODS: Between December 2003 and December 2015, 249 consecutive RTSAs were performed at our hospital. Of these, 68 primary uncemented RTSA met our inclusion criteria. The Constant-Murley score (CMS), the modified Constant score, a visual analog scale (VAS) and active shoulder range of motion (ROM) were measured pre- and postoperatively. Radiological assessment was performed by plain radiographs at a minimum of 5 years postoperatively. RESULTS: At a mean follow-up of 80.2 months, there was no significant difference (p = .59) between the postoperative functional scores and range of motion of the two groups (Delta Xtend and Lima SMR). Radiological data of stress-shielding were observed in 38 patients (55.9%) being slightly more frequent in the Lima SMR group (21 patients) than in the Delta Xtend group (17 patients) (p = .62). CONCLUSIONS: Our study shows that the good functional results are similar between the two uncemented RTSA systems used and that they do not depend on the presence of radiological changes (stress-shielding) in the humeral stem at a minimum 5-year follow-up.


Assuntos
Artroplastia do Ombro , Úmero , Radiografia , Amplitude de Movimento Articular , Prótese de Ombro , Humanos , Artroplastia do Ombro/métodos , Feminino , Masculino , Seguimentos , Idoso , Radiografia/métodos , Pessoa de Meia-Idade , Úmero/diagnóstico por imagem , Úmero/cirurgia , Desenho de Prótese , Resultado do Tratamento , Articulação do Ombro/cirurgia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/fisiopatologia , Estudos Retrospectivos
15.
J Subst Use Addict Treat ; 161: 209341, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38490334

RESUMO

BACKGROUND: North America has been in an unrelenting overdose crisis for almost a decade. British Columbia (BC), Canada declared a public health emergency due to overdoses in 2016. Risk Mitigation Guidance (RMG) for prescribing pharmaceutical opioids, stimulants and benzodiazepine alternatives to the toxic drug supply ("safer supply") was implemented in March 2020 in an attempt to reduce harms of COVID-19 and overdose deaths in BC during dual declared public health emergencies. Our objective was to describe early implementation of RMG among prescribers in BC. METHODS: We conducted a convergent mixed methods study drawing population-level linked administrative health data and qualitative interviews with 17 prescribers. The Consolidated Framework for Implementation Research (CFIR) informs our work. The study utilized seven linked databases, capturing the characteristics of prescribers for people with substance use disorder to describe the characteristics of those prescribing under the RMG using univariate summary statistics and logistic regression analysis. For the qualitative analysis, we drew on interpretative descriptive methodology to identify barriers and facilitators to implementation. RESULTS: Analysis of administrative databases demonstrated limited uptake of the intervention outside large urban centres and a highly specific profile of urban prescribers, with larger and more complex caseloads associated with RMG prescribing. Nurse practitioners were three times more likely to prescribe than general practitioners. Qualitatively, the study identified five themes related to the five CFIR domains: 1) RMG is helpful but controversial; 2) Motivations and challenges to prescribing; 3) New options and opportunities for care but not enough to 'win the arms race'; 4) Lack of implementation support and resources; 5) Limited infrastructure. CONCLUSIONS: BC's implementation of RMG was limited in scope, prescriber uptake and geographic scale up. Systemic, organizational and individual barriers and facilitators point to the importance of engaging professional regulatory colleges, implementation planning and organizational infrastructure to ensure effective implementation and adaptation to context.


Assuntos
COVID-19 , Humanos , Colúmbia Britânica/epidemiologia , COVID-19/epidemiologia , Overdose de Drogas/tratamento farmacológico , Analgésicos Opioides/intoxicação , Analgésicos Opioides/efeitos adversos , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Benzodiazepinas/provisão & distribuição , Benzodiazepinas/uso terapêutico , Benzodiazepinas/intoxicação , Pesquisa Qualitativa , Feminino , Masculino
16.
Br J Cancer ; 130(10): 1670-1678, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38486123

RESUMO

BACKGROUND: The Colorectal Cancer Subtyping Consortium established four Consensus Molecular Subtypes (CMS) in colorectal cancer: CMS1 (microsatellite-instability [MSI], Immune), CMS2 (Canonical, epithelial), CMS3 (Metabolic), and CMS4 (Mesenchymal). However, only MSI tumour patients have seen a change in their disease management in clinical practice. This study aims to characterise the proteome of colon cancer CMS and broaden CMS's clinical utility. METHODS: One-hundred fifty-eight paraffin samples from stage II-III colon cancer patients treated with adjuvant chemotherapy were analysed through DIA-based mass-spectrometry proteomics. RESULTS: CMS1 exhibited overexpression of immune-related proteins, specifically related to neutrophils, phagocytosis, antimicrobial response, and a glycolytic profile. These findings suggested potential therapeutic strategies involving immunotherapy and glycolytic inhibitors. CMS3 showed overexpression of metabolic proteins. CMS2 displayed a heterogeneous protein profile. Notably, two proteomics subtypes within CMS2, with different protein characteristics and prognoses, were identified. CMS4 emerged as the most distinct group, featuring overexpression of proteins related to angiogenesis, extracellular matrix, focal adhesion, and complement activation. CMS4 showed a high metastatic profile and suggested possible chemoresistance that may explain its worse prognosis. CONCLUSIONS: DIA proteomics revealed new features for each colon cancer CMS subtype. These findings provide valuable insights into potential therapeutic targets for colorectal cancer subtypes in the future.


Assuntos
Neoplasias do Colo , Proteômica , Humanos , Proteômica/métodos , Neoplasias do Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/metabolismo , Feminino , Masculino , Prognóstico , Idoso , Pessoa de Meia-Idade , Instabilidade de Microssatélites , Quimioterapia Adjuvante , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
17.
Hip Int ; 34(4): 467-475, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38529883

RESUMO

INTRODUCTION: Ceramic-on-ceramic bearings have been widely used since their introduction in the 1970s. First-generation ceramics have very high fracture (breakage) rates. To overcome this, in the 1990s, modular cotyloid insert designs were developed, consisting of a ceramic and polyethylene composite (sandwich-type) liner; however, high implant fracture rates were observed in the medium term. We aimed to estimate the cumulative incidences of revision surgery (implant failure) and implant failure due to fractures, survival rates (time-to-revision surgery and time-to-fracture), and the long-term clinical and radiological outcomes in our series. METHODS: This was an observational, longitudinal, ambispective, single-centre study based on patients who underwent primary total hip arthroplasty (THA) using a sandwich-type liner (Cerasul), only available in our tertiary hospital between January 1999 and December 2002. Cumulative incidences were estimated and the 95% confidence interval (95% CI) was calculated. The Kaplan-Meier method was used to assess the time-to-revision surgery and time-to-fracture. RESULTS: 54 patients (49 men) were included, accounting for 59 sandwich-type linear implants. The mean (range) age was 47.4 (22-57) years. The primary THA indications were osteoarthritis (28 patients), osteonecrosis (14), childhood pathology sequelae (11), and inflammatory arthritis (6). The cumulative incidence of revision surgery by implants was 8.5% (5/59, 95% CI, 3.5-19.2%), 9.3% by patients (5/54, 95% CI, 4.0-19.9%), and 5.1% by implant fractures (3/59, 95%CI, 1.7-13.9%). The median (Interquartile Range, IQR) time-to-revision surgery was 158 (72.5-161) months, and the time to fracture was 182 (138-215) months. All primary THAs had good clinical and long-term survival outcomes. All implants had signs of solid fixation. CONCLUSIONS: After a 20-year follow-up period, the polyethylene-ceramic sandwich-type liner showed a long survival rate and low cumulative incidence of implant fracture; however, implant fractures remain the main complication. Orthopaedic surgeons should be aware that some patients still have this type of prosthesis and must be capable of responding quickly if a fracture occurs.


Assuntos
Artroplastia de Quadril , Cerâmica , Prótese de Quadril , Polietileno , Desenho de Prótese , Falha de Prótese , Reoperação , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Artroplastia de Quadril/métodos , Seguimentos , Adulto , Fatores de Tempo , Idoso , Estudos Retrospectivos , Estudos Longitudinais , Resultado do Tratamento
18.
J Leukoc Biol ; 116(1): 77-83, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38547424

RESUMO

The physiological and molecular responses of leukocytes are altered by organophosphate pesticides. Some reports have shown that diazinon causes immunotoxic effects; diazoxon, the oxon metabolite of diazinon, is attributed to influence the immune response by affecting the leukocyte cholinergic system. In this study, the in vitro effects of diazoxon on molecules involved in cell signaling (cAMP, IP3, DAG, JAK1, and STAT3), which play a crucial role in the activation, differentiation, and survival of leukocytes, were evaluated. Data indicate that diazoxon leads to a decrease in cAMP concentration and an increase in basal IP3 levels. However, diazoxon does not affect basal levels of JAK1 and STAT3 phosphorylation. Instead, diazoxon inhibits leukocyte responsiveness to phorbol myristate acetate and ionomycin, substances that, under normal conditions, enhance JAK/STAT signaling. These findings demonstrate that diazoxon significantly affects key molecular parameters related to cell signaling.


Assuntos
Leucócitos , Sistemas do Segundo Mensageiro , Transdução de Sinais , Animais , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sistemas do Segundo Mensageiro/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , AMP Cíclico/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Janus Quinase 1/metabolismo , Fosforilação/efeitos dos fármacos , Ionomicina/farmacologia , Inseticidas/toxicidade , Inseticidas/farmacologia , Compostos Organofosforados
19.
Sci Rep ; 14(1): 3544, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347059

RESUMO

Acute poisonings are a global public health problem, which implies costs and disease burden for society. In Colombia, there is a significant underreporting of data on acute poisoning and data gaps on the toxicological profile of the population. This study aims to identify the epidemiology of acute poisoning in a high-complexity hospital in southwestern Colombia. A descriptive study with retrospective data collection was performed. The variables were expressed through the measure of central tendency and dispersion. Categorical variables were described in proportions. A total of 406 patients were included. The median age was 31 years (IQR 23-48), 56.2% were male, and only 19.2% had a history of mental illness. Suicidal intent represented 58.8% of the cases, and the most frequent route of exposure was the oral route (81.6%). The most prevalent groups of substances were pesticides (34.2%) and medicines (32%). The most common etiological agent was organophosphates (16.5%). Cholinergic toxidrome was the most common. The average stay in the ICU was 4.5 days (± 4.8), and the mortality was 4.2%. The principal causes of acute poisoning were drugs and pesticides, with a predominant etiology of organophosphates and depressants of the central nervous system. There was a significant predominance of young male patients with suicidal intent, low mental disorders, elevated unemployment rate, and similar mortality reported in other studies. This study improves the knowledge about acute poisoning in southwestern Colombian to carry out multicenter analytic studies.


Assuntos
Praguicidas , Intoxicação , Adulto , Feminino , Humanos , Masculino , Colômbia/epidemiologia , Serviço Hospitalar de Emergência , Hospitais Universitários , Organofosfatos , Estudos Retrospectivos
20.
J Virol ; 98(3): e0170323, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38353535

RESUMO

The increased detection of H3 C-IVA (1990.4.a) clade influenza A viruses (IAVs) in US swine in 2019 was associated with a reassortment event to acquire an H1N1pdm09 lineage nucleoprotein (pdmNP) gene, replacing a TRIG lineage NP (trigNP). We hypothesized that acquiring the pdmNP conferred a selective advantage over prior circulating H3 viruses with a trigNP. To investigate the role of NP reassortment in transmission, we identified two contemporary 1990.4.a representative strains (NC/19 and MN/18) with different evolutionary origins of the NP gene. A reverse genetics system was used to generate wild-type (wt) strains and swap the pdm and TRIG lineage NP genes, generating four viruses: wtNC/19-pdmNP, NC/19-trigNP, wtMN/18-trigNP, and MN/18-pdmNP. The pathogenicity and transmission of the four viruses were compared in pigs. All four viruses infected 10 primary pigs and transmitted to five indirect contact pigs per group. Pigs infected via contact with MN/18-pdmNP shed virus 2 days earlier than pigs infected with wtMN/18-trigNP. The inverse did not occur for wtNC/19-pdmNP and NC/19-trigNP. This suggests that pdmNP reassortment resulted in a combination of genes that improved transmission efficiency when paired with the 1990.4.a hemagglutinin (HA). This is likely a multigenic trait, as replacing the trigNP gene did not diminish the transmission of a wild-type IAV in swine. This study demonstrates how reassortment and evolutionary change of internal genes can result in more transmissible viruses that influence HA clade detection frequency. Thus, rapidly identifying novel reassortants paired with dominant hemagglutinin/neuraminidase may improve the prediction of strains to include in vaccines.IMPORTANCEInfluenza A viruses (IAVs) are composed of eight non-continuous gene segments that can reassort during coinfection of a host, creating new combinations. Some gene combinations may convey a selective advantage and be paired together preferentially. A reassortment event was detected in swine in the United States that involved the exchange of two lineages of nucleoprotein (NP) genes (trigNP to pdmNP) that became a predominant genotype detected in surveillance. Using a transmission study, we demonstrated that exchanging the trigNP for a pdmNP caused the virus to shed from the nose at higher levels and transmit to other pigs more rapidly. Replacing a pdmNP with a trigNP did not hinder transmission, suggesting that transmission efficiency depends on interactions between multiple genes. This demonstrates how reassortment alters IAV transmission and that reassortment events can provide an explanation for why genetically related viruses with different internal gene combinations experience rapid fluxes in detection frequency.


Assuntos
Vírus da Influenza A , Proteínas do Nucleocapsídeo , Infecções por Orthomyxoviridae , Doenças dos Suínos , Animais , Hemaglutininas , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Infecções por Orthomyxoviridae/veterinária , Infecções por Orthomyxoviridae/virologia , Vírus Reordenados/genética , Suínos , Estados Unidos , Proteínas do Nucleocapsídeo/metabolismo
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