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1.
Genetica ; 152(2-3): 71-81, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888686

RESUMO

Freshwater ecosystems are among the most endangered ecosystems worldwide. While numerous taxa are on the verge of extinction as a result of global changes and direct or indirect anthropogenic activity, genomic and transcriptomic resources represent a key tool for comprehending species' adaptability and serve as the foundation for conservation initiatives. The Loire grayling, Thymallus ligericus, is a freshwater European salmonid endemic to the upper Loire River basin. The species is comprised of fragmented populations that are dispersed over a small area and it has been identified as a vulnerable species. Here, we provide a multi-tissue de novo transcriptome assembly of T. ligericus. The completeness and integrity of the transcriptome were assessed before and after redundancy removal with lineage-specific libraries from Eukaryota, Metazoa, Vertebrata, and Actinopterygii. Relative gene expression was assessed for each of the analyzed tissues, using the de novo assembled transcriptome and a genome-based analysis using the available T. thymallus genome as a reference. The final assembly, with a contig N50 of 1221 and Benchmarking Universal Single-Copy Orthologs (BUSCO) scores above 94%, is made accessible along with structural and functional annotations and relative gene expression of the five tissues (NCBI SRA and FigShare databases). This is the first transcriptomic resource for this species, which provides a foundation for future research on this and other salmonid species that are increasingly exposed to environmental stressors.


Assuntos
Salmonidae , Transcriptoma , Animais , Salmonidae/genética , Água Doce , Anotação de Sequência Molecular , Perfilação da Expressão Gênica , Espécies em Perigo de Extinção , Genoma
2.
Neurosurg Focus ; 56(6): E12, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38823042

RESUMO

OBJECTIVE: The aim of this study was 1) to describe the rate of intrathecal baclofen (ITB)-associated complications at a large tertiary center, and 2) to evaluate the impact of patient-related factors on the likelihood of developing such complications. METHODS: A retrospective single-center study was carried out. A total of 301 eligible patients were included in the analysis. Univariate regression models were used to evaluate the impact of age, sex, diagnosis, ambulation status, modified Ashworth scale score, body mass index, diabetes status, and pain level on the likelihood of developing a device-related infection, pump malfunction, catheter malfunction, and other clinically significant complications. RESULTS: Overall, 27% of patients experienced an ITB-related complication. The most common complications included infection (6%, 18/301), pump malfunction (7.3%, 22/301), and catheter malfunction (14%, 42/301). The univariate analyses revealed that the patient's ambulatory status had a significant impact on the likelihood of developing a catheter-related malfunction. Furthermore, a trend toward significance was identified between patients' preoperative body mass index and device-related infection. Finally, the risk of suffering any ITB-related complications was statistically correlated with the number of years that had passed since the initial pump implantation. CONCLUSIONS: The authors' analysis reveals a previously underrecognized association between ambulatory status at the time of ITB pump implantation and the incidence of catheter-related complications, and confirms the impact of time since surgery on the risk of developing any ITB-related complication. The patient's age, sex, diagnosis, diabetes status, or pain level at baseline were not associated with the risk of complications. Collectively, these insights contribute novel information to the existing literature, providing practical value for physicians in guiding patient selection for ITB therapy.


Assuntos
Baclofeno , Bombas de Infusão Implantáveis , Injeções Espinhais , Relaxantes Musculares Centrais , Humanos , Baclofeno/administração & dosagem , Baclofeno/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Fatores de Risco , Bombas de Infusão Implantáveis/efeitos adversos , Relaxantes Musculares Centrais/administração & dosagem , Relaxantes Musculares Centrais/efeitos adversos , Injeções Espinhais/efeitos adversos , Idoso , Adulto Jovem , Espasticidade Muscular/tratamento farmacológico , Falha de Equipamento/estatística & dados numéricos , Adolescente
3.
Gen Dent ; 72(4): 31-36, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38905602

RESUMO

Hearing impairments and dental anomalies are found in many genetic syndromes. Otodental syndrome is a rare combination of hearing loss and the presence of a pathognomonic dental phenotype known as globodontia, in which the tooth exhibits an abnormal globe shape. There is no histologic evidence of structural anomalies in the enamel, dentin, or pulp. This report describes the case of a 12-year-old boy who had hearing loss and 2 supernumerary globe-shaped teeth in the sites of the permanent maxillary central incisors. The diagnosis of otodental syndrome was established based on the clinical, radiographic, and histologic features, but other conditions, including dens evaginatus, talon cusp, dens invaginatus, and compound odontoma, should be included in the differential diagnosis. Dental treatment consisted of the extraction of both anomalous teeth, allowing spontaneous eruption of the impacted permanent central incisors. Early diagnosis of otodental syndrome permits a multidisciplinary approach to prevent other pathologic conditions, reduce functional damage, and avoid social problems.


Assuntos
Incisivo , Humanos , Masculino , Criança , Incisivo/anormalidades , Dente Supranumerário/complicações , Dente Supranumerário/diagnóstico por imagem , Dente Supranumerário/cirurgia , Anormalidades Dentárias/diagnóstico , Diagnóstico Diferencial , Anormalidades Múltiplas , Doenças do Desenvolvimento Ósseo , Deficiência Intelectual , Fácies
4.
J Neurosci ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38724284

RESUMO

While ipsilesional cortical electroencephalography has been associated with post-stroke recovery mechanisms and outcomes, the role of cerebellum and its interaction with the ipsilesional cortex is still largely unknown. We have previously shown that post-stroke motor control relies on increased cortico-cerebellar coherence (CCC) in the low beta band to maintain motor task accuracy and to compensate for decreased excitability of the ipsilesional cortex. We now extend our work to investigate corticocerebellar network changes associated with chronic stimulation of the dentato-thalamo-cortical pathway aimed at promoting post-stroke motor rehabilitation. We investigated the excitability of ipsilesional cortex, dentate (DN), and their interaction as a function of treatment outcome measures. Relative to baseline, ten human participants (two women) at the end of 4-8 months of DN deep brain stimulation (DBS) showed 1) significantly improved motor control indexed by computerized motor tasks; 2) significant increase in ipsilesional premotor cortex event-related desynchronization that correlated with improvements in motor function; and 3) significant decrease in CCC, including causal interactions between the DN and ipsilesional cortex, which also correlated with motor function improvements. Furthermore, we show that the functional state of the DN in the post-stroke state and its connectivity with ipsilesional cortex were predictive of motor outcomes associated with DN-DBS. The findings suggest that as participants recovered, the ipsilesional cortex became more involved in motor control, with less demand on the cerebellum to support task planning and execution. Our data provide unique mechanistic insights into the functional state of cortico-cerebellar-cortical network after stroke and its modulation by DN-DBS.Significance Statement The study aims to understand the brain mechanisms underlying the effects of cerebellar dentate deep brain stimulation (DN-DBS), a novel upcoming therapy for chronic stroke. We provide evidence that functional improvements as a result of DN-DBS therapy were accompanied by significant improvements in task behavior and ipsilesional cortex excitability. More importantly.

7.
Exp Neurol ; 376: 114751, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38484864

RESUMO

Despite great advances in acute care and rehabilitation, stroke remains the leading cause of motor impairment in the industrialized world. We have developed a deep brain stimulation (DBS)-based approach for post-stroke rehabilitation that has shown reproducible effects in rodent models and has been recently translated to humans. Mechanisms underlying the rehabilitative effects of this novel therapy have been largely focused on the ipsilesional cortex, including cortical reorganization, synaptogenesis, neurogenesis and greater expression of markers of long-term potentiation. The role of subcortical structures on its therapeutic benefits, particularly the striatum, remain unclear. In this study, we compared the motor rehabilitative effects of deep cerebellar stimulation in two rodent models of cerebral ischemia: a) cortical ischemia; and b) combined striatal and cortical ischemia. All animals underwent the same procedures, including implantation of the electrodes and tethered connections for stimulation. Both experimental groups received four weeks of continuous lateral cerebellar nucleus (LCN) DBS and each was paired with a no stimulation, sham, group. Fine motor function was indexed using the pasta matrix task. Brain tissue was harvested for histology and immunohistochemical analyses. In the cortical-only ischemia, the average pasta matrix performance of both sham and stimulated groups reduced from 19 to 24 pieces to 7-8 pieces following the stroke induction. At the end of the four-week treatment, the performance of stimulated group was significantly greater than that of sham group (14 pieces vs 7 pieces, p < 0.0001). Similarly, in the combined cortical and striatal ischemia, the performance of both sham and stimulated groups reduced from 29 to 30 pieces to 7-11 pieces following the stroke induction. However, at the end of the four-week treatment, the performance of stimulated group was not significantly greater than that of sham group (15 pieces vs 11 pieces, p = 0.452). In the post-mortem analysis, the number of cells expressing CaMKIIα at the perilesional cortical and striatum of the LCN DBS treated animals receiving cortical-only stroke elevated but not those receiving cortical+striatal stroke. The current findings suggested that the observed, LCN DBS-enhanced motor recovery and perilesional plasticity may involve striatal mechanisms.


Assuntos
Corpo Estriado , Estimulação Encefálica Profunda , AVC Isquêmico , Recuperação de Função Fisiológica , Animais , Estimulação Encefálica Profunda/métodos , Recuperação de Função Fisiológica/fisiologia , Masculino , AVC Isquêmico/terapia , AVC Isquêmico/fisiopatologia , AVC Isquêmico/patologia , Corpo Estriado/patologia , Ratos , Ratos Sprague-Dawley , Cerebelo/patologia , Reabilitação do Acidente Vascular Cerebral/métodos
8.
World Neurosurg ; 185: e1177-e1181, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508382

RESUMO

OBJECTIVE: The primary aim of this study is to report long-term outcomes associated with deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) performed at our institution. We further aimed to elicit the factors associated with loss of efficacy and to discuss the need for exploring and establishing reliable rescue targets. METHODS: To study long-term outcomes, we performed a retrospective chart review and extracted tremor scores of 43 patients who underwent VIM DBS lead implantation for essential tremor at our center. We further evaluated factors that could influence outcomes over time, including demographics, body mass index, duration of follow-up, degree of parenchymal atrophy indexed by the global cortical atrophy scale, and third ventricular width. RESULTS: In this cohort, tremor scores on the latest follow-up (median 52.7 months) were noted to be worse than initial postoperative scores in 56% of DBS leads. Furthermore, 14% of leads were associated with clinically significant loss of benefit. Factors including the length of time since the lead implantation, age at the time of surgery, sex, body mass index, preoperative atrophy, and third ventricular width were not predictive of long-term outcomes. CONCLUSIONS: Our study identified a substantial subgroup of VIM-DBS patient who experienced a gradual decline in treatment efficacy over time. We propose that this phenomenon can be attributed primarily to habituation and disease progression. Furthermore, we discuss the need to establish reliable and effective rescue targets for this subpopulation of patients, with ventral-oralis complex and dentate nucleus emerging as potential candidates.


Assuntos
Estimulação Encefálica Profunda , Tremor Essencial , Humanos , Tremor Essencial/terapia , Tremor Essencial/cirurgia , Estimulação Encefálica Profunda/métodos , Feminino , Masculino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Núcleos Ventrais do Tálamo/cirurgia , Idoso de 80 Anos ou mais , Seguimentos , Adulto
9.
Mar Genomics ; 74: 101084, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38485292

RESUMO

The Annelida phylum is composed of a myriad of species exhibiting key phenotypic adaptations. They occupy key ecological niches in a variety of marine, freshwater and terrestrial ecosystems. Importantly, the increment of omic resources is rapidly modifying the taxonomic landscape and knowledge of species belonging to this phylum. Here, we comprehensively characterised and annotated a transcriptome of the common ragworm, Hediste diversicolor (OF Müller). This species belongs to the family Nereididae and inhabits estuarine and lagoon areas on the Atlantic coasts of Europe and North America. Ecologically, H. diversicolor plays an important role in benthic food webs. Given its commercial value, H. diversicolor is a promising candidate for aquaculture development and production in farming facilities, under a circular economy framework. We used Illumina next-generation sequencing technology, to produce a total of 105 million (M) paired-end (PE) raw reads and generate the first whole-body transcriptome assembly of H. diversicolor species. This high-quality transcriptome contains 69,335 transcripts with an N50 transcript length of 2313 bp and achieved a BUSCO gene completeness of 97.7% and 96% in Eukaryota and Metazoa lineage-specific profile libraries. Our findings offer a valuable resource for multiple biological applications using this species.


Assuntos
Ecossistema , Poliquetos , Animais , Transcriptoma , Poliquetos/genética , Aquicultura , Europa (Continente)
10.
Genes (Basel) ; 15(2)2024 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-38397160

RESUMO

The European sardine (Sardina pilchardus, Walbaum 1792) is indisputably a commercially important species. Previous studies using uneven sampling or a limited number of makers have presented sometimes conflicting evidence of the genetic structure of S. pilchardus populations. Here, we show that whole genome data from 108 individuals from 16 sampling areas across 5000 km of the species' distribution range (from the Eastern Mediterranean to the archipelago of Azores) support at least three genetic clusters. One includes individuals from Azores and Madeira, with evidence of substructure separating these two archipelagos in the Atlantic. Another cluster broadly corresponds to the center of the distribution, including the sampling sites around Iberia, separated by the Almeria-Oran front from the third cluster that includes all of the Mediterranean samples, except those from the Alboran Sea. Individuals from the Canary Islands appear to belong to the Mediterranean cluster. This suggests at least two important geographical barriers to gene flow, even though these do not seem complete, with many individuals from around Iberia and the Mediterranean showing some patterns compatible with admixture with other genetic clusters. Genomic regions corresponding to the top outliers of genetic differentiation are located in areas of low recombination indicative that genetic architecture also has a role in shaping population structure. These regions include genes related to otolith formation, a calcium carbonate structure in the inner ear previously used to distinguish S. pilchardus populations. Our results provide a baseline for further characterization of physical and genetic barriers that divide European sardine populations, and information for transnational stock management of this highly exploited species towards sustainable fisheries.


Assuntos
Peixes , Metagenômica , Humanos , Animais , Peixes/genética , Portugal , Genoma/genética , Espanha
11.
Neuroimage ; 289: 120556, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38423263

RESUMO

Functional neuroimaging methods like fMRI and PET are vital in neuroscience research, but require that subjects remain still throughout the scan. In animal research, anesthetic agents are typically applied to facilitate the acquisition of high-quality data with minimal motion artifact. However, anesthesia can have profound effects on brain metabolism, selectively altering dynamic neural networks and confounding the acquired data. To overcome the challenge, we have developed a novel head fixation device designed to support awake rat brain imaging. A validation experiment demonstrated that the device effectively minimizes animal motion throughout the scan, with mean absolute displacement and mean relative displacement of 0.0256 (SD: 0.001) and 0.009 (SD: 0.002), across eight evaluated subjects throughout fMRI image acquisition (total scanning time per subject: 31 min, 12 s). Furthermore, the awake scans did not induce discernable stress to the animals, with stable physiological parameters throughout the scan (Mean HR: 344, Mean RR: 56, Mean SpO2: 94 %) and unaltered serum corticosterone levels (p = 0.159). In conclusion, the device presented in this paper offers an effective and safe method of acquiring functional brain images in rats, allowing researchers to minimize the confounding effects of anesthetic use.


Assuntos
Anestésicos , Vigília , Humanos , Ratos , Animais , Vigília/fisiologia , Encéfalo/fisiologia , Cabeça , Neuroimagem/métodos , Imageamento por Ressonância Magnética/métodos , Anestésicos/farmacologia
12.
Meat Sci ; 212: 109463, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38401357

RESUMO

Pork belly brining is a time-consuming step of bacon production that needs to be studied and enhanced through suitable technologies. In this sense, this study aimed at evaluating the impact of ultrasound (US), mechanical agitation (AG), and static brine (SB) on the kinetics of water loss (WL), solids gain (SG), and salt content (SC) of pork belly during brining under different temperatures. Mathematical models were used to estimate mass transfer rates, equilibrium parameters, and thermodynamic properties. Peleg model was chosen as the most suitable model to predict the kinetics experimental data (Radj2 ≥ 0.979 and RMSE ≤ 0.014). The increase in the brine temperature increased WL, SG, and SC for all treatments. Nonlinear effects of temperature were observed for WL, SG, and SC, following an Arrhenius-type behavior. The assistance of ultrasound significantly enhanced the velocity of WL, SG, and SC by 32-56%, while AG improved by 18-39% both compared to SB. Brining was considered an endothermic and non-spontaneous process through the thermodynamic assessment. The increase in temperature and the AG and US processes accelerated the formation of the activated complex. The application of ultrasound was considered the most suitable technology to reduce the brining time. However, significant improvements can be obtained by mechanical agitation. Therefore, both methods can be used to reduce the time processing of pork belly aiming at accelerating the bacon production process.


Assuntos
Carne de Porco , Carne Vermelha , Animais , Carne Vermelha/análise , Sais , Cloreto de Sódio , Cloreto de Sódio na Dieta , Suínos
13.
Fish Shellfish Immunol ; 147: 109431, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38346567

RESUMO

Paracentrotus lividus is the most abundant echinoid species in the North East Atlantic Ocean and Mediterranean Sea. Although there is abundant genomic information of the species, there is no deep characterisation of the genes involved in the immune response. Here, a reference transcriptome of male and female coelomocytes was produced. The generated P. lividus transcriptome assembly has 203,511 transcripts, N50 transcript length of 1079 bp, and more than 90% estimated gene completeness in Eukaryota and Metazoa BUSCO databases, respectively. Differential gene expression analyses showed 54 and 55 up-regulated genes in P. lividus female and male coelomocyte tissues, respectively. These results suggest a similar immune gene repertoire between sexes. To examine the immune response, P. lividus was challenged with Vibrio anguillarum, one of the candidate pathogens for bald disease. Immune parameters were evaluated at cell and humoral levels, as well as the expression analysis of immune related genes at an early response stage. No differences were found at cellular and humoral levels with the exception of the increase of nitric oxide in perivisceral fluid of challenged animals. At the gene expression level, a total of 2721 genes were upregulated in challenged animals, 13.6 times higher expression than control group. Our analysis revealed that four major KEGG pathways were enriched in challenged animals: Autophagy (KEGG:04140), Endocytosis (KEGG:04144), Phagosome (KEGG:04145) and Protein processing in endoplasmic reticulum (KEGG:04141). Several toll-like receptors (TLR), scavenger receptors cysteine-rich (SRCR) or nucleotide-binding oligomerisation domain like receptors (NLR) were identified as major family genes for pathogen recognition and immune defence. This study provides a valuable transcriptomic resource and unfolds the molecular basis of immune response to V. anguillarum exposure. Overall, our findings contribute to the conservation effort of the P. lividus populations, as well as its sustainable exploitation in an aquaculture context.


Assuntos
Paracentrotus , Vibrio , Feminino , Masculino , Animais , Vibrio/fisiologia , Fagocitose , Receptores Toll-Like
14.
Colloids Surf B Biointerfaces ; 234: 113747, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38219639

RESUMO

This study investigates the interaction between sakuranetin, a versatile pharmaceutical flavonoid, and monolayers composed of unsaturated phospholipids, serving as a surrogate for cell membranes. The phospholipids were 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE). We conducted a series of experiments to comprehensively investigate this interaction, including surface pressure assessments, Brewster angle microscopy (BAM), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Our findings unequivocally demonstrate that sakuranetin interacts with these phospholipids, expanding the monomolecular films. Notably, regarding POPC, the presence of sakuranetin led to a reduction in stability and a decline in surface elasticity, which can likely be attributed to intricate molecular rearrangements at the interface. The visual evidence of aggregations in BAM images reinforces the interactions substantiated by PM-IRRAS, highlighting sakuranetin's interaction with the polar and nonpolar regions of POPC. However, it is worth noting that these aggregations do not appear to contribute significantly to the viscosity of the mixed film, and our investigations did not reveal any substantial hysteresis. In contrast, when examining POPE, we observed a minor reduction in thermodynamic stability, indicative of fewer rearrangements within the monolayer. This notion was further reinforced by the limited presence of aggregations in the BAM images. Sakuranetin also increased the rigidity of the lipid monolayer; nevertheless, the monolayer remained predominantly elastic, facilitating easy re-spreading on the surface, especially for the first lipid. PM-IRRAS analysis unveiled interactions between sakuranetin and POPE's polar and nonpolar segments, compellingly explaining the observed monolayer expansion. Taken together, our data suggest that sakuranetin was more effectively incorporated into the monomolecular layer of POPE, indicating that membranes comprised of POPC might exhibit a greater degree of interaction in the presence of this pharmacologically active compound.


Assuntos
Fosfolipídeos , Fitoalexinas , Água , Água/química , Propriedades de Superfície , Fosfolipídeos/química , Flavonoides
15.
J Neurosurg ; 140(3): 849-855, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37877998

RESUMO

OBJECTIVE: High accuracy and precision are essential in stereotactic neurosurgery, as targeting errors can significantly affect clinical outcomes. Image registration is a vital step in stereotaxis, and understanding the error associated with different image registration methods is important to inform the choice of equipment and techniques in stereotactic neurosurgery. The authors aimed to quantify the test-retest reliability and stereotactic accuracy of cone-beam CT (CBCT) compared with the current clinical gold-standard technique (i.e., CT). METHODS: Two anthropomorphic phantom models with 40 independent unique steel spheres were developed to compare CBCT frame and stereotactic space registration with the clinical gold standard (CT). The cartesian coordinates of each sphere were compared between the imaging modalities for test-retest reliability and overall accuracy. RESULTS: Both imaging modalities showed similar levels of fiducial deviation from the expected geometry. The equivalence test demonstrated mean differences between CT and CBCT registration of -0.082 mm (90% CI -0.27 to 0.11), -0.045 mm (90% CI -0.43 to 0.34), and -0.041 mm (90% CI -0.064 to 0.018) for coordinates in the x-, y-, and z-axes, respectively. The mean euclidean distance difference between the two modalities was 0.28 mm (90% CI 0.27-0.29). CONCLUSIONS: Accuracy and precision were comparable between CBCT and CT image registrations. These findings suggest that CBCT registration can be used as a clinically equivalent substitute to gold-standard CT acquisition.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional , Humanos , Reprodutibilidade dos Testes , Tomografia Computadorizada de Feixe Cônico/métodos , Imageamento Tridimensional/métodos , Imagens de Fantasmas
16.
AIDS ; 38(1): 31-38, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37696248

RESUMO

OBJECTIVE: To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation. DESIGN: Multicenter, retrospective cohort study. METHODS: We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS). We assessed the utility of MLR, anemia severity and in combination, for predicting TB in the first year after ART. Cox regression was used to assess associations of MLR and anemia with incident TB. Harrell's C index was used to describe single model discrimination. RESULTS: A total of 1455 participants with a median age of 34 [interquartile range (IQR) 29, 41] were included. Fifty-four participants were diagnosed with TB. The hazard ratio (HR) for incident TB was 1.77 [95% confidence interval (CI) 1.01-3.07]; P  = 0.04 for those with MLR ≥0.23. The HR for mild/mod anemia was 3.35 (95% CI 1.78-6.29; P  < 0.001) and 18.16 (95% CI 5.17-63.77; P  < 0.001) for severe anemia. After combining parameters, there were increases in adjusted HR (aHR) for MLR ≥0.23 to 1.83 (95% CI 1.05-3.18), and degrees of anemia to 3.38 (95% CI 1.80-6.35) for mild/mod anemia and 19.09 (95% CI 5.43-67.12) for severe anemia. CONCLUSIONS: MLR and hemoglobin levels which are available in routine HIV care can be used at ART initiation for identifying patients at high risk of developing TB disease to guide diagnostic and management decisions.


Assuntos
Anemia , Infecções por HIV , Tuberculose , Humanos , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Estudos Retrospectivos , Monócitos/química , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Tuberculose/complicações , Incidência , Anemia/epidemiologia , Anemia/complicações , Anemia/diagnóstico , Linfócitos , Hemoglobinas/análise , Contagem de Linfócito CD4
17.
Neurorehabil Neural Repair ; 38(2): 109-121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38156644

RESUMO

BACKGROUND: Cerebellum shares robust di-synaptic dentato-thalamo-cortical (DTC) connections with the contralateral motor cortex. Preclinical studies have shown that DTC are excitatory in nature. Structural integrity of DTC is associated with better upper extremity (UE) motor function in people with stroke, indicating DTC are important for cerebellar influences on movement. However, there is a lack of understanding of physiologic influence of DTC in humans, largely due to difficulty in accessing the dentate nucleus. OBJECTIVE: Characterize DTC physiology using dentate nucleus deep brain stimulation (DBS) combined with transcranial magnetic stimulation (TMS) in stroke. METHODS: Nine chronic stroke survivors with moderate-to-severe UE impairment (Fugl-Meyer 13-38) underwent a paired DBS-TMS experiment before receiving experimental dentate nucleus DBS in our first-in-human phase I trial (Baker et al., 2023, Nature Medicine). Conditioning DBS pulses were given to dentate nucleus 1 to 10 ms prior to supra-threshold TMS pulses given to ipsilesional motor cortex. Effects were assessed on motor evoked potentials (MEPs). Size of DBS-conditioned MEPs was expressed relative to TMS MEPs, where values >1 indicate facilitation. RESULTS: Dentate nucleus DBS led to facilitation of MEPs at short-latency intervals (3.5 and 5 ms, P = .049 and .021, respectively), a phenomenon we have termed dentato-cortical facilitation (DCF). Higher DCF was observed among patients with more severe UE impairment. Diffusion tensor imaging revealed microstructure of thalamo-cortical portion of DTC was related to higher corticomotor excitability. CONCLUSIONS: Our in vivo investigation reveals for the first time in humans the intrinsic excitatory properties of DTC, which can serve as a novel therapeutic target for post-stroke motor recovery.


Assuntos
Acidente Vascular Cerebral , Estimulação Magnética Transcraniana , Humanos , Cerebelo , Imagem de Tensor de Difusão , Potencial Evocado Motor/fisiologia , Acidente Vascular Cerebral/terapia , Estimulação Magnética Transcraniana/métodos , Extremidade Superior , Ensaios Clínicos Fase I como Assunto
18.
Nat Med ; 29(12): 3162-3174, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38049620

RESUMO

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .


Assuntos
Lesões Encefálicas Traumáticas , Estimulação Encefálica Profunda , Humanos , Lesões Encefálicas Traumáticas/terapia , Estimulação Encefálica Profunda/métodos , Estudos de Viabilidade , Qualidade de Vida , Tálamo/fisiologia
19.
Int Tinnitus J ; 27(1): 6-9, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38050878

RESUMO

Chiari Malformations are a group of conditions defined in 1891 with 5 degrees being described. These malformations present with several symptoms such as cervical protrusion and are associated with hydrocephalus. Also, they can also present with different clinical signs and symptoms, such as deafness and tinnitus. We present a case of a 45-year-old man with unilateral tinnitus evaluated in otolaryngology office. No other symptoms on otolaryngological physical exam were detected in the audiogram performed it was described a significant unilateral sensorineural hearing loss. During the study of this patient, Magnetic Resonance Imaging was requested, showing a type I Chiari malformation. The patient was then observed by Ophthalmology, Neurology, and Neurosurgery. No other neurological symptoms of malformation Chiari syndrome or cranial nerve abnormalities were presented at the respective exam. The surgical management of these pathologies takes into account an adequate CSF and venous blood flow - that was seen in this patient, therefore, there was no surgical indication for decompression. The patient maintains its follow-up in the otolaryngology, neurology, and neurosurgery office, and tinnitus was minimized after prosthetic adaptation was recommended to optimize the quality of life, which was achieved.


Assuntos
Malformação de Arnold-Chiari , Perda Auditiva Neurossensorial , Zumbido , Masculino , Humanos , Pessoa de Meia-Idade , Zumbido/etiologia , Zumbido/complicações , Qualidade de Vida , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/diagnóstico , Malformação de Arnold-Chiari/cirurgia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva Neurossensorial/cirurgia , Imageamento por Ressonância Magnética/efeitos adversos
20.
Crit. Care Sci ; 35(4): 367-376, Oct.-Dec. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1528492

RESUMO

ABSTRACT Objective: To assess the impact of different vertical positions on lung aeration in patients receiving invasive mechanical ventilation. Methods: An open-label randomized crossover clinical trial was conducted between January and July 2020. Adults receiving invasive mechanical ventilation for > 24 hours and < 7 days with hemodynamic, respiratory and neurological stability were randomly assigned at a 1:1 ratio to the sitting position followed by passive orthostasis condition or the passive orthostasis followed by the sitting position condition. The primary outcome was lung aeration assessed using the lung ultrasound score (score ranges from 0 [better] to 36 [worse]). Results: A total of 186 subjects were screened; of these subjects, 19 were enrolled (57.8% male; mean age, 73.2 years). All participants were assigned to receive at least one verticalization protocol. Passive orthostasis resulted in mean lung ultrasound scores that did not differ significantly from the sitting position (11.0 versus 13.7; mean difference, -2.7; [95%CI -6.1 to 0.71; p = 0.11). Adverse events occurred in three subjects in the passive orthostasis group and in one in the sitting position group (p = 0.99). Conclusion: This analysis did not find significant differences in lung aeration between the sitting and passive orthostasis groups. A randomized crossover clinical trial assessing the impact of vertical positioning on lung aeration in patients receiving invasive mechanical ventilation is feasible. Unfortunately, the study was interrupted due to the need to treat COVID-19 patients. ClinicalTrials.gov registry: NCT04176445


RESUMO Objetivo: Avaliar o impacto de diferentes posicionamentos verticais na aeração pulmonar em pacientes em ventilação mecânica invasiva. Métodos: Trata-se de ensaio clínico aberto, randomizado e transversal, realizado entre janeiro e julho de 2020. Adultos em ventilação mecânica invasiva por mais de 24 horas e menos de 7 dias com estabilidade hemodinâmica, respiratória e neurológica foram distribuídos aleatoriamente em uma proporção de 1:1 à postura sentada seguida da condição de ortostatismo passivo ou o ortostatismo passivo seguido de postura sentada. O desfecho primário foi a aeração pulmonar avaliada pelo lung ultrasound score. O escore varia de zero (melhor) a 36 (pior). Resultados: Foram selecionados 186 indivíduos; destes, 19 foram incluídos (57,8% do sexo masculino; média idade de 73,2 anos). Todos os participantes foram selecionados para receber pelo menos um protocolo de verticalização. O ortostatismo passivo resultou em escores médios de aeração pulmonar por ultrassonografia que não diferiram significativamente da postura sentada (11,0 versus 13,7; diferença média, -2,7; IC95% -6,1 a 0,71; p = 0,11). Ocorreram eventos adversos em três indivíduos no grupo ortostatismo passivo e em um no grupo postura sentada (p = 0,99). Conclusão: Esta análise não encontrou diferenças significativas na aeração pulmonar entre os grupos ortostatismo passivo e postura sentada. É factível conduzir um estudo clínico transversal randomizado para avaliar o impacto do posicionamento vertical na aeração pulmonar em pacientes em ventilação mecânica invasiva. Infelizmente, o estudo foi interrompido devido à necessidade de tratar pacientes com COVID-19. Registro ClinicalTrials.gov: NCT04176445

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