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1.
J Wildl Dis ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041231

RESUMO

Two of 19 roe deer (Capreolus capreolus) in northern Spain were infested with Cephenemyia stimulator and one individual with Oestrus ovis. Three larvae of O. ovis were recovered from the nasopharynx of an adult female deer examined in February 2017, during the hunting season in the province of Burgos. The larvae were identified by morphology, and DNA sequencing from cytochrome oxidase subunit I and 28S rDNA confirmed the identification of both species of larvae. The possibility of O. ovis parasitizing roe deer should be considered in the diagnosis of nasal bots in cervids.

2.
Methods Mol Biol ; 2819: 357-379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39028515

RESUMO

Architectural DNA-binding proteins are key to the organization and compaction of genomic DNA inside cells. The activity of architectural proteins is often subject to further modulation and regulation through the interaction with a diverse array of other protein factors. Detailed knowledge on the binding modes involved is crucial for our understanding of how these protein-protein and protein-DNA interactions shape the functional landscape of chromatin in all kingdoms of life: bacteria, archaea, and eukarya.Microscale thermophoresis (MST) is a biophysical technique for the study of biomolecular interactions. It has seen increasing application in recent years thanks to its solution-based nature, rapid application, modest sample demand, and the sensitivity of the thermophoresis effect to binding events.Here, we describe the use of MST in the study of chromatin interactions. The emphasis lies on the wide range of ways in which these experiments are set up and the diverse types of information they reveal. These aspects are illustrated with four very different systems: the sequence-dependent DNA compaction by architectural protein HMfB, the sequential binding of core histone complexes to histone chaperone APLF, the impact of the nucleosomal context on the recognition of histone modifications, and the binding of a viral peptide to the nucleosome. Special emphasis is given to the key steps in the design, execution, and analysis of MST experiments in the context of the provided examples.


Assuntos
Cromatina , Histonas , Nucleossomos , Ligação Proteica , Cromatina/metabolismo , Cromatina/genética , Nucleossomos/metabolismo , Histonas/metabolismo , DNA/metabolismo , DNA/química , DNA/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química , Chaperonas de Histonas/metabolismo
3.
Methods Mol Biol ; 2819: 443-454, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39028518

RESUMO

DNA looping is important for genome organization in all domains of life. The basis of DNA loop formation is the bridging of two separate DNA double helices. Detecting DNA bridge formation generally involves the use of complex single-molecule techniques (atomic force microscopy, magnetic or optical tweezers). Although DNA bridging can be qualitatively described, quantification of DNA bridging and bridging dynamics using these techniques is challenging. Here we describe a biochemical assay capable of not only detecting DNA bridge formation but also allowing for quantification of DNA bridging efficiency and the quantification of the effects of physicochemical conditions or protein interaction partners on DNA bridge formation.


Assuntos
Cromatina , DNA , DNA/química , Cromatina/metabolismo , Cromatina/química , Cromatina/genética , Microscopia de Força Atômica/métodos , Conformação de Ácido Nucleico , Pinças Ópticas , Humanos
4.
Methods Mol Biol ; 2819: 477-496, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39028520

RESUMO

Architectural DNA-binding proteins are key to the organization and compaction of genomic DNA inside cells. Tethered particle motion (TPM) permits analysis of DNA conformation and detection of changes in conformation induced by such proteins at the single molecule level in vitro. As many individual protein-DNA complexes can be investigated in parallel, these experiments have high throughput. TPM is therefore well suited for characterization of the effects of protein-DNA stoichiometry and changes in physicochemical conditions (pH, osmolarity, and temperature). Here, we describe in detail how to perform tethered particle motion experiments on complexes between DNA and architectural proteins to determine their structural and biochemical characteristics.


Assuntos
Proteínas de Ligação a DNA , DNA , Conformação de Ácido Nucleico , DNA/química , DNA/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química , Ligação Proteica , Imagem Individual de Molécula/métodos , Movimento (Física)
5.
Artigo em Inglês | MEDLINE | ID: mdl-39028630

RESUMO

High altitude (HA) hypoxia lowers uterine artery (UtA) blood flow during pregnancy and birth weight. Adenosine monophosphate kinase (AMPK) activation has selective, uteroplacental vasodilator effects which lessen hypoxia-associated birth weight reductions. In this study, we determined the relationship between AMPK-pathway gene expression and metabolites in the maternal circulation during HA pregnancy as well as with the maintenance of UtA blood flow and birth weight at HA. HA (2793 m) vs low altitude (LA; 1640 m) residents had smaller UtA diameters at weeks 20 and 34, lower UtA blood flow at week 20, and lower birth weight babies. At week 34, HA vs LA women had decreased expression of up- and down-stream AMPK-pathway genes. Expression of the a-1 AMPK catalytic subunit, PRKAA1, correlated positively with UtA diameter and blood flow at week 20 (HA) and 34 (LA). Downstream AMPK-pathway gene expression positively correlated with week 20 fetal biometry at both altitudes and with UtA diameter and birth weight at LA. Reduced gene expression of AMPK activators and downstream targets in HA versus LA women, together with positive correlations between PRKAA1 gene expression, UtA diameter, and blood flow suggest that greater sensitivity to AMPK activation at mid-gestation at HA may help offset later depressant effects of hypoxia on fetal growth.

6.
Viruses ; 16(6)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38932214

RESUMO

Human adenovirus-36 (HAdV-36) infection has been linked to obesity, low lipid levels, and improvements in blood glucose levels and insulin sensitivity in animal models and humans, although epidemiological studies remain controversial. Therefore, this study investigated the relationship between HAdV-36 seropositivity and glycemic control in youths. This observational study examined 460 youths (246 with normal weight and 214 obese subjects). All participants underwent assessments for anthropometry, blood pressure, circulating fasting levels of glucose, lipids, insulin, and anti-HAdV-36 antibodies; additionally, the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. In all, 57.17% of the subjects were HAdV-36 seropositive. Moreover, HAdV-36 seroprevalence was higher in obese subjects compared to their normal weight counterparts (59% vs. 55%). BMI (33.1 vs. 32.3 kg/m2, p = 0.03), and waist circumference (107 vs. 104 cm, p = 0.02), insulin levels (21 vs. 16.3 µU/mL, p = 0.003), and HOMA-IR (4.6 vs. 3.9, p = 0.02) were higher in HAdV-36-positive subjects with obesity compared to seronegative subjects. In the obese group, HAdV-36 seropositivity was associated with a reducing effect in blood glucose levels in a model adjusted for total cholesterol, triglyceride levels, age and sex (ß = -10.44, p = 0.014). Furthermore, a statistically significant positive relationship was observed between HAdV-36 seropositivity and insulin levels in the obesity group. These findings suggest that natural HAdV-36 infection improves glycemic control but does not ameliorate hyperinsulinemia in obese subjects.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Glicemia , Resistência à Insulina , Insulina , Obesidade , Humanos , Masculino , Feminino , Glicemia/análise , Insulina/sangue , Adolescente , Obesidade/sangue , Infecções por Adenovirus Humanos/sangue , Infecções por Adenovirus Humanos/epidemiologia , Infecções por Adenovirus Humanos/virologia , Criança , Estudos Soroepidemiológicos , Adulto Jovem , Índice de Massa Corporal , Anticorpos Antivirais/sangue
7.
BioData Min ; 17(1): 15, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38863014

RESUMO

The development of neuroscientific techniques enabling the recording of brain and peripheral nervous system activity has fueled research in cognitive science. Recent technological advancements offer new possibilities for inducing behavioral change, particularly through cost-effective Internet-based interventions. However, limitations in laboratory equipment volume have hindered the generalization of results to real-life contexts. The advent of Internet of Things (IoT) devices, such as wearables, equipped with sensors and microchips, has ushered in a new era in behavior change techniques. Wearables, including smartwatches, electronic tattoos, and more, are poised for massive adoption, with an expected annual growth rate of 55% over the next five years. These devices enable personalized instructions, leading to increased productivity and efficiency, particularly in industrial production. Additionally, the healthcare sector has seen a significant demand for wearables, with over 80% of global consumers willing to use them for health monitoring. This research explores the primary biometric applications of wearables and their impact on users' well-being, focusing on the integration of behavior change techniques facilitated by IoT devices. Wearables have revolutionized health monitoring by providing real-time feedback, personalized interventions, and gamification. They encourage positive behavior changes by delivering immediate feedback, tailored recommendations, and gamified experiences, leading to sustained improvements in health. Furthermore, wearables seamlessly integrate with digital platforms, enhancing their impact through social support and connectivity. However, privacy and data security concerns must be addressed to maintain users' trust. As technology continues to advance, the refinement of IoT devices' design and functionality is crucial for promoting behavior change and improving health outcomes. This study aims to investigate the effects of behavior change techniques facilitated by wearables on individuals' health outcomes and the role of wearables in promoting a healthier lifestyle.

8.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38892353

RESUMO

Mycobacterium bovis (Mb) is the causative agent of bovine tuberculosis (bTb). Genetic selection aiming to identify less susceptible animals has been proposed as a complementary measure in ongoing programs toward controlling Mb infection. However, individual animal phenotypes for bTb based on interferon-gamma (IFNÉ£) and its use in bovine selective breeding programs have not been explored. In the current study, IFNÉ£ production was measured using a specific IFNÉ£ ELISA kit in bovine purified protein derivative (bPPD)-stimulated blood samples collected from Holstein cattle. DNA isolated from the peripheral blood samples collected from the animals included in the study was genotyped with the EuroG Medium Density bead Chip, and the genotypes were imputed to whole-genome sequences. A genome-wide association analysis (GWAS) revealed that the IFNÉ£ in response to bPPD was associated with a specific genetic profile (heritability = 0.23) and allowed the identification of 163 SNPs, 72 quantitative trait loci (QTLs), 197 candidate genes, and 8 microRNAs (miRNAs) associated with this phenotype. No negative correlations between this phenotype and other phenotypes and traits included in the Spanish breeding program were observed. Taken together, our results define a heritable and distinct immunogenetic profile associated with strong production of IFNÉ£ in response to Mb.


Assuntos
Estudo de Associação Genômica Ampla , Interferon gama , Mycobacterium bovis , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Tuberculose Bovina , Animais , Bovinos , Mycobacterium bovis/imunologia , Interferon gama/genética , Interferon gama/metabolismo , Tuberculose Bovina/genética , Tuberculose Bovina/imunologia , Tuberculose Bovina/microbiologia , Fenótipo , Genótipo
9.
Nature ; 631(8019): 179-188, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38926578

RESUMO

Encouraging routine COVID-19 vaccinations is likely to be a crucial policy challenge for decades to come. To avert hundreds of thousands of unnecessary hospitalizations and deaths, adoption will need to be higher than it was in the autumn of 2022 or 2023, when less than one-fifth of Americans received booster vaccines1,2. One approach to encouraging vaccination is to eliminate the friction of transportation hurdles. Previous research has shown that friction can hinder follow-through3 and that individuals who live farther from COVID-19 vaccination sites are less likely to get vaccinated4. However, the value of providing free round-trip transportation to vaccination sites is unknown. Here we show that offering people free round-trip Lyft rides to pharmacies has no benefit over and above sending them behaviourally informed text messages reminding them to get vaccinated. We determined this by running a megastudy with millions of CVS Pharmacy patients in the United States testing the effects of (1) free round-trip Lyft rides to CVS Pharmacies for vaccination appointments and (2) seven different sets of behaviourally informed vaccine reminder messages. Our results suggest that offering previously vaccinated individuals free rides to vaccination sites is not a good investment in the United States, contrary to the high expectations of both expert and lay forecasters. Instead, people in the United States should be sent behaviourally informed COVID-19 vaccination reminders, which increased the 30-day COVID-19 booster uptake by 21% (1.05 percentage points) and spilled over to increase 30-day influenza vaccinations by 8% (0.34 percentage points) in our megastudy. More rigorous testing of interventions to promote vaccination is needed to ensure that evidence-based solutions are deployed widely and that ineffective but intuitively appealing tools are discontinued.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Sistemas de Alerta , Meios de Transporte , Vacinação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Prática Clínica Baseada em Evidências , Educação em Saúde/métodos , Educação em Saúde/estatística & dados numéricos , Política de Saúde/tendências , Imunização Secundária/estatística & dados numéricos , Vacinas contra Influenza/administração & dosagem , Farmácias/estatística & dados numéricos , Sistemas de Alerta/classificação , Sistemas de Alerta/estatística & dados numéricos , Envio de Mensagens de Texto/estatística & dados numéricos , Fatores de Tempo , Meios de Transporte/economia , Meios de Transporte/métodos , Estados Unidos , Vacinação/estatística & dados numéricos
10.
Chempluschem ; : e202400210, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38895895

RESUMO

The advancements in the capabilities of artificial sensory technologies, such as electronic/optical noses and tongues, have significantly enhanced their ability to identify complex mixtures of analytes. These improvements are rooted in the evolving manufacturing processes of cross-reactive sensor arrays (CRSAs) and the development of innovative computational methods. The potential applications in early diagnosis, food quality control, environmental monitoring, and more, position CRSAs as an exciting area of research for scientists from diverse backgrounds. Among these, plasmonic CRSAs are particularly noteworthy because they offer enhanced capabilities for remote, fast, and even real-time monitoring, in addition to better portability of instrumentation. Specifically, the synergy between the localized surface plasmon resonance (LSPR) of nanoparticles (NPs) and CRSAs introduces advanced techniques such as surface plasmon resonance (SPR), metal-enhanced fluorescence (MEF), surface-enhanced infrared absorption (SEIRA), surface-enhanced Raman scattering (SERS), and surface-enhanced resonance Raman scattering (SERRS) spectroscopies. This review delves into the importance and versatility of optical-CRSAs, especially those based on plasmonic materials, discussing recent applications and potential new research directions.

11.
Heliyon ; 10(9): e29935, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707311

RESUMO

Trained immunity (TRAIM) or the enhanced non-specific immune response after primary stimulation by infection or vaccination is a recent but well-recognized concept. To verify its predictions, our objective was to determine the effects of two bacterial vaccines, typhoid fever (TFV) and diphtheria-tetanus-pertussis (DTP) on the infection, hospitalization and death frequencies associated to COVID-19 in a retrospective study on subjects vaccinated or not with TFV and DTP in the 4 years prior to the start of COVID-19 pandemia in the Basque Country (Spain). The studied outcome records were split into two periods according to COVID-19 vaccination, the pre-vaccination (ACV) from March to December 2020 and the post-vaccination (PCV) from September 2021 to June 2022). In total, 13,673 subjects were vaccinated against TFV and 42,997 against DTP. A total of 2,005,084 individual records were studied in the ACV period and 1,436,693 in the PCV period. The proportion of infection, hospitalization and death associated to COVID-19 among controls in ACV was 4.97 %, 7.14 % and 3.54 %, respectively vs. 7.20 %, 2.24 % and 0.10 % among TFV subjects. Regarding DTP, the proportions were 4.97 %, 7.12 % and 3.58 % for controls and 5.79 %, 5.79 % and 0.80 % for vaccinees. In the PCV period, the proportion of infection, hospitalization and death among controls was 21.89 %, 2.62 % and 0.92 %, respectively vs. 31.19 %, 0.76 %, 0.00 % among TFV. For DTP, infection, hospitalization and death proportions were 21.89 %, 2.62 % and 0.92 %, respectively, among controls vs. 32.03 %, 1.85 % and 0.24 % among vaccinated subjects. The corresponding combined ACV and PCV odds ratios (OR) for SARS-CoV2 infection were 1.505 (95%CI 1.455-1.558; p < 0.0001; reduction -41.85 %) and 1.633 (95%CI 1.603-1.662; p < 0.0001; reduction -51.74 %), for TFV and DTP, respectively. Regarding COVID-19 associated hospitalization, the OR were 0.295 (95%CI 0.220-0.396; p = 0.0001; reduction 69.74 %) and 0.667 (95%CI 0.601-0.741; p = 0.0001; reduction 32.44 %), for TFV and DTP, respectively). COVID-19 associated death OR were 0.016 (95%CI 0.002-0.113, p < 0.0001; reduction 98.38 %) and 0.212 (95%CI 0.161-0.280; p = 0.0001; reduction 78.52 %), for TFV and DTP, respectively. We conclude that TRAIM effects by TFV and DTP vaccination in the four years prior to the pandemic SARS-CoV2 were supported by slightly increased infection rates, but strongly reduced COVID-19 associated hospitalization and death rates.

12.
Plast Reconstr Surg Glob Open ; 12(5): e5830, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38784833

RESUMO

For autologous breast reconstruction using the deep inferior epigastric perforator flap, the internal mammary vessels are a common choice for recipient vessels. However, if these vessels are discovered to be inadequate, this may require the utilization of alternative vessels for successful salvage. Here, we demonstrate the use of a venous conduit for flap salvage in a patient undergoing bilateral deep inferior epigastric perforator flap breast reconstruction. Intraoperative venous congestion was identified on the left side. A contributing factor was an unresolvable size discrepancy between the deep inferior epigastric and the internal mammary venae comitantes. A saphenous vein graft can be used to drain the donor inferior epigastric vein to the contralateral internal mammary venae comitantes. In this discussion, adequate venous drainage was obtained with this approach, and the flap remained viable with good Doppler signals without further complications over a year postoperatively.

13.
medRxiv ; 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38798492

RESUMO

Objectives: Hispanic/Latino adults have a high prevalence of uncontrolled hypertension predisposing them to CVD. We hypothesize that sleep apnea severity is associated with uncontrolled blood pressure (BP) and resistant hypertension in Hispanic/Latino adults. Methods: This was a cross-sectional study of 2,849 Hispanic Community Health Study/Study of Latinos participants with hypertension (i.e., systolic BP ≥130 mm Hg, or diastolic BP ≥80 mm Hg or self-reported antihypertensive medication use) who were taking at least one class of antihypertensive medication. Participants were categorized as having controlled (BP < 130/80 mmHg among those on hypertension treatment) , uncontrolled (BP ≥ 130/80 mmHg using one or two classes of antihypertensive medications), or resistant hypertension (BP ≥ 130/80 mmHg while on ≥ 3 classes of antihypertensive medications or the use of ≥ 4 classes of antihypertensive medications regardless of BP control). Sleep apnea was classified based on the respiratory event index (REI; events/h) as mild (REI ≥ 5 and < 15), moderate-to-severe (REI ≥ 15), or no sleep apnea (REI < 5). Results: In multinomial logistic regression, moderate-to-severe sleep apnea (vs. no sleep apnea) was associated with higher odds of resistant hypertension (Odds Ratio [OR], 2.15; 95% CI, 1.36-3.39 at 4% desaturation and OR 1.68; 95% CI, 1.05-2.67 at 3% desaturation). Neither mild nor moderate-to-severe sleep apnea was associated with uncontrolled hypertension. Conclusion: Among diverse Hispanic/Latino persons, moderate-to-severe but not mild sleep apnea was associated with resistant hypertension. Identification and management of sleep apnea in this population may improve BP control and subsequently prevent adverse cardiovascular outcomes.

14.
Commun Chem ; 7(1): 115, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796547

RESUMO

The quest for environmentally sustainable materials spans many fields and applications including optical materials. Here, we present the development of light filters using a gelatin-based nanocomposite. Owing to the plasmonic properties of metallic nanoparticles (NPs), strong light-matter interactions, these filters can be customized across the UV-Visible-NIR spectrum. The filters are designed for modular use, allowing for the addition or removal of desired spectral ranges. Moreover, the nanocomposites are composed of biodegradable and biocompatible materials which highlight the intersection of chemistry and ecological awareness for the exploration of new eco-friendly alternatives. These plasmonic gelatin-based filters block light due to the Localized Surface Plasmon Resonance (LSPR) of the NPs and can be tailored to meet various requirements, akin to a diner selecting options from a menu. This approach is inspired by culinary techniques, and we anticipate it will stimulate further exploration of biomaterials for applications in optics, materials science or electronics.

16.
Laryngoscope ; 134(8): 3713-3718, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38525993

RESUMO

OBJECTIVE: To estimate the current prevalence of voice disorders among adults in the United States; to determine the association of individual factors with voice disorders. METHODS: The 2022 National Health Interview Survey (NHIS) was analyzed to identify adults reporting voice problems in the past 12 months. Demographics were assessed, as well as the duration, severity, and resolution of the voice problem. The relationship between voice problems, gender, lost workdays, and long COVID was investigated. A comparison to the 2012 NHIS was made to determine changes in voice disorder prevalence. RESULTS: 29.9 million Americans (95%CI[28.3-31.5]) annually report a voice problem, representing 12.2% of the population (95%CI[11.7-12.8%]). Overall, 26.8% and 13.2% reported the severity of their voice problem as moderate or severe, respectively. Only 5.1% (95%CI[4.3-6.0%]) of respondents sought treatment. Most voice problems were resolved within 1 week (53.0%,95%CI[50.9-55.1%]). Females were more likely than males to report a voice problem (14.4% vs. 10.0%,95%CI[13.7-15.1] and [9.3-10.7], respectively). The 17.6 million Americans with long COVID symptoms were more likely to have voice complaints than those without (21.1% vs. 11.6%,95%CI[18.9-23.5%] and [11.1-12.1%], respectively). Lost workdays were not significantly higher for those with voice disorders compared to those without (17.1 vs. 12.9 days,95%CI[12.0-22.1] and [11.0-14.8], respectively). CONCLUSIONS: Voice problems affect approximately 1 in 8 adults in the U.S. annually, demonstrating an alarming increased prevalence since 2012 using the same survey methodology. Relatively few individuals seek care for their voice problem, despite significant self-reported impact. Further study is required regarding the impact of COVID and changes in voice use patterns on voice disorders. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3713-3718, 2024.


Assuntos
COVID-19 , Distúrbios da Voz , Humanos , COVID-19/epidemiologia , Distúrbios da Voz/epidemiologia , Masculino , Estados Unidos/epidemiologia , Feminino , Prevalência , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , SARS-CoV-2 , Adolescente , Inquéritos Epidemiológicos
18.
Vet Res ; 55(1): 41, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532491

RESUMO

Tuberculosis BCG vaccination induced non-specific protective effects in humans led to postulate the concept of trained immunity (TRAIM) as an innate type of immune mechanism that triggered by a pathogen, protects against others. Killed vaccines have been considered not to be effective. However, field efficacy of a commercial vaccine against paratuberculosis, as well as of a recently developed M. bovis heat-inactivated vaccine (HIMB) prompted to test whether it could also induce TRAIM. To this, we used a sarcoptic mange rabbit model. Twenty-four weaned rabbits were treated orally or subcutaneously with a suspension of either HIMB (107 UFC) or placebo. Eighty-four days later the animals were challenged with approximately 5000 S. scabiei mites on the left hind limb. Skin lesion extension was measured every 2 weeks until 92 days post-infection (dpi). Two animals were killed at 77 dpi because of extensive skin damage. The rest were euthanized and necropsied and the lesion area and the mite burden per squared cm were estimated. Specific humoral immune responses to S. scabiei and to M. bovis were investigated with the corresponding specific ELISA tests. Subcutaneously and orally HIMB vaccinated animals compared with placebo showed reduced lesion scores (up to 74% and 62%, respectively) and mite counts (-170% and 39%, respectively). This, together with a significant positive correlation (r = 0.6276, p = 0.0031) between tuberculosis-specific antibodies and mite count at 92 dpi supported the hypothesis of non-specific effects of killed mycobacterial vaccination. Further research is needed to better understand this mechanism to maximize cross protection.


Assuntos
Mycobacterium bovis , Escabiose , Tuberculose , Humanos , Coelhos , Animais , Escabiose/prevenção & controle , Escabiose/veterinária , Tuberculose/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Imunidade Humoral , Vacinas de Produtos Inativados , Vacina BCG
19.
Neurobiol Dis ; 193: 106437, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367882

RESUMO

TDP-43 pathology is found in several neurodegenerative disorders, collectively referred to as "TDP-43 proteinopathies". Aggregates of TDP-43 are present in the brains and spinal cords of >97% of amyotrophic lateral sclerosis (ALS), and in brains of ∼50% of frontotemporal dementia (FTD) patients. While mutations in the TDP-43 gene (TARDBP) are usually associated with ALS, many clinical reports have linked these mutations to cognitive impairments and/or FTD, but also to other neurodegenerative disorders including Parkinsonism (PD) or progressive supranuclear palsy (PSP). TDP-43 is a ubiquitously expressed, highly conserved RNA-binding protein that is involved in many cellular processes, mainly RNA metabolism. To investigate systemic pathological mechanisms in TDP-43 proteinopathies, aiming to capture the pleiotropic effects of TDP-43 mutations, we have further characterised a mouse model carrying a point mutation (M323K) within the endogenous Tardbp gene. Homozygous mutant mice developed cognitive and behavioural deficits as early as 3 months of age. This was coupled with significant brain structural abnormalities, mainly in the cortex, hippocampus, and white matter fibres, together with progressive cortical interneuron degeneration and neuroinflammation. At the motor level, progressive phenotypes appeared around 6 months of age. Thus, cognitive phenotypes appeared to be of a developmental origin with a mild associated progressive neurodegeneration, while the motor and neuromuscular phenotypes seemed neurodegenerative, underlined by a progressive loss of upper and lower motor neurons as well as distal denervation. This is accompanied by progressive elevated TDP-43 protein and mRNA levels in cortex and spinal cord of homozygous mutant mice from 3 months of age, together with increased cytoplasmic TDP-43 mislocalisation in cortex, hippocampus, hypothalamus, and spinal cord at 12 months of age. In conclusion, we find that Tardbp M323K homozygous mutant mice model many aspects of human TDP-43 proteinopathies, evidencing a dual role for TDP-43 in brain morphogenesis as well as in the maintenance of the motor system, making them an ideal in vivo model system to study the complex biology of TDP-43.


Assuntos
Esclerose Lateral Amiotrófica , Demência Frontotemporal , Proteinopatias TDP-43 , Animais , Pré-Escolar , Humanos , Camundongos , Esclerose Lateral Amiotrófica/metabolismo , Encéfalo/metabolismo , Cognição , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/patologia , Proteinopatias TDP-43/genética , Proteinopatias TDP-43/patologia
20.
Epilepsia ; 65(4): 873-886, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38305763

RESUMO

The current pace of development and applications of large language models (LLMs) is unprecedented and will impact future medical care significantly. In this critical review, we provide the background to better understand these novel artificial intelligence (AI) models and how LLMs can be of future use in the daily care of people with epilepsy. Considering the importance of clinical history taking in diagnosing and monitoring epilepsy-combined with the established use of electronic health records-a great potential exists to integrate LLMs in epilepsy care. We present the current available LLM studies in epilepsy. Furthermore, we highlight and compare the most commonly used LLMs and elaborate on how these models can be applied in epilepsy. We further discuss important drawbacks and risks of LLMs, and we provide recommendations for overcoming these limitations.


Assuntos
Inteligência Artificial , Epilepsia , Humanos , Registros Eletrônicos de Saúde , Epilepsia/diagnóstico , Epilepsia/terapia , Idioma
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