Search

The purpose of this article is to review the scientific literature concerning speech in Parkinson’s disease (PD) with reference to the DIVA/GODIVA neurocomputational modeling framework. Within this theoretical view, the basal ganglia (BG) contribute to several different aspects of speech motor learning and execution. First, the BG are posited to play a role in the initiation and scaling of speech movements. Within the DIVA/GODIVA framework, initiation and scaling are carried out by initiation map nodes in the supplementary motor area acting in concert with the BG. Reduced support of the initiation map from the BG in PD would result in reduced movement intensity as well as susceptibility to early termination of movement. A second proposed role concerns the learning of common speech sequences, such as phoneme sequences comprising words; this view receives support from the animal literature as well as studies identifying speech sequence learning deficits in PD. Third, the BG may play a role in the temporary buffering and sequencing of longer speech utterances such as phrases during conversational speech. Although the literature does not support a critical role for the BG in representing sequence order (since incorrectly ordered speech is not characteristic of PD), the BG are posited to contribute to the scaling of individual movements in the sequence, including increasing movement intensity for emphatic stress on key words. Therapeutic interventions for PD have inconsistent effects on speech. In contrast to dopaminergic treatments, which typically either leave speech unchanged or lead to minor improvements, deep brain stimulation (DBS) can degrade speech in some cases and improve it in others. However, cases of degradation may be due to unintended stimulation of efferent motor projections to the speech articulators. Findings of spared speech after bilateral pallidotomy appear to indicate that any role played by the BG in adult speech must be supplementary rather than mandatory, with the sequential order of well-learned sequences apparently represented elsewhere (e.g., in cortico-cortical projections).

Abstract MARCKS (myristoylated alanine-rich C-kinase substrate) is a membrane-associated protein expressed in many cell types, including macrophages. MARCKS is functionally implicated in cell adhesion, phagocytosis, and inflammation. LPS (lipopolysaccharide) triggers inflammation via TLR4 (toll-like receptor 4).The presence of MARCKS and the formation of phospho-MARCKS in various cell types have been described, but the role(s) of MARCKS in regulating macrophage functions remain unclear. We investigated the role of MARCKS in inflammation. Confocal microscopy revealed that MARCKS and phospho-MARCKS increased localization to endosomes and the Golgi apparatus upon LPS stimulation.CRISPR-CAS9 mediated knockout of MARCKS in macrophages downregulated the production of TNF and IL6, suggesting a role for MARCKS in inflammatory responses. Our comprehensive proteomics analysis together with real-time metabolic assays comparing LPS-stimulation of WT and MARCKS knock-out macrophages provided insights into the involvement of MARCKS in specific biological processes including innate immune response, inflammatory response, cytokine production, and molecular functions such as extracellularly ATP-gated cation channel activity, electron transfer activity and oxidoreductase activity, uncovering specific proteins involved in regulating MARCKS activity upon LPS stimulation. MARCKS appears to be a key regulator of inflammation whose inhibition might be beneficial for therapeutic intervention in inflammatory diseases.

For the 701 mammals that occur in Brazil (ca. 13% of extant mammals worldwide), we attributed ES to each deliverer one based on their functional traits, known trophic interactions, expert knowledge, and by overlaying IUCN's distribution maps of the species. The ES term encompasses both ecosystem processes and services, offering a broader perspective that enables us to investigate the potential benefits of mammals to people. We assumed that species that are currently listed as threatened in the IUCN most likely lost their ES role. We found that 82% of Brazilian mammals (575 spp.) deliver at least one of the 11 ES identified. Cultural services were associated with the greatest number of deliverer species, while carrion control, ecosystem engineering, and rodent control were delivered by fewer species. Although only 24% of the species analyzed here are endemic to Brazil, 75% of them deliver at least one ES. The ES they delivered are also disproportionately at risk, as 57% of the species considered to have lost their ES role are endemic. Ecosystem service provision does not merely mirror the spatial patterns of mammal richness in general, as we identified hotspots for each service across Brazil, including its seascapes. Our comprehensive assessment provides a clear overview of the myriad of services delivered by Brazilian mammals, including taxonomic and spatial explicit information for each service. Identifying and mapping species and their services can contribute to more effective management and conservation programs focused on optimizing the supply of ES and conserving biodiversity.

Small island developing states (SIDS) are experiencing climate change not just as a threat to their lifestyle, but as an immediate threat to their existence. Climate change poses unique risks to these islands, due to their small size, low-lying nature, lack of infrastructure, and minimal adaptation resources. Furthermore, climate change impacts the sea more than most other ecosystems. Ninety percent of global warming is occurring in the world’s oceans. Because SIDS are exceptionally dependent on the ocean for natural resources and various sources of income, their continued existence is dependent upon both fighting climate change and protecting oceans.This paper will argue that the international tools being used to protect the world’s oceans can also be effective tools to fight climate change. As greenhouse gas emissions continue to intensify ocean warming and irreparably harm ocean resources, SIDS can argue that these emissions violate internationa ltreaties and customary law meant to protect the ocean and its resources.This paper will also propose three concrete ways that legal advocates for SIDS—activists, lawyers, government actors, and NGOs—can use these arguments: First, the arguments can be brought to the International Court of Justice to request an advisory opinion focusing specifically on emissions causing ocean warming. Second, they can be brought to the International Tribunal on the Law of the Sea with the same request. Finally, they can be codified into a new treaty committed specifically to slowing the warming of the world’s oceans.

Brain–computer interfaces (BCIs) are pivotal in translating neural activities into control commands for external assistive devices. Non-invasive techniques like electroencephalography (EEG) offer a balance of sensitivity and spatial-temporal resolution for capturing brain signals associated with motor activities. This work introduces MOVING, a Multi-Modal dataset of EEG signals and Virtual Glove Hand Tracking. This dataset comprises neural EEG signals and kinematic data associated with three hand movements—open/close, finger tapping, and wrist rotation—along with a rest period. The dataset, obtained from 11 subjects using a 32-channel dry wireless EEG system, also includes synchronized kinematic data captured by a Virtual Glove (VG) system equipped with two orthogonal Leap Motion Controllers. The use of these two devices allows for fast assembly (∼1 min), although introducing more noise than the gold standard devices for data acquisition. The study investigates which frequency bands in EEG signals are the most informative for motor task classification and the impact of baseline reduction on gesture recognition. Deep learning techniques, particularly EEGnetV4, are applied to analyze and classify movements based on the EEG data. This dataset aims to facilitate advances in BCI research and in the development of assistive devices for people with impaired hand mobility. This study contributes to the repository of EEG datasets, which is continuously increasing with data from other subjects, which is hoped to serve as benchmarks for new BCI approaches and applications.

Background: Gastroesophageal reflux disease (GERD) is a challenging condition that involves different physicians, such as general practitioners (GPs), gastroenterologists, and ears, nose and throat (ENT) specialists. A common approach consists of proton-pump inhibitors (PPIs) administration. Adjunctive pharmacological treatment may have a role in the management of non-responders to PPIs. Objectives: We aimed to survey GPs and different medical specialists to investigate the medical approaches to patients reporting GERD symptoms. In addition, we examined the use of adjunctive pharmacological treatments in patients with GERD symptoms who do not respond to PPIs. Design: Retrospective observational study. Methods: A survey was conducted among a large sample of gastroenterologists, GPs, and ENT specialists. Symptoms were divided into typical and extraesophageal, and their severity and impact on quality of life were explored with the GERD Impact Scale and with Reflux Symptom Index (RSI). All therapies administered usually for GERD were investigated. Results: A total of 6211 patients were analyzed in this survey. Patients with typical symptoms were 53.5%, while those with extraesophageal symptoms were 46.5%. The latter were more frequently reported by ENT patients (53.6%, p

Low-velocity impacts represent a critical dynamic condition for engineering structures. Combining two reinforcing fibers in a single matrix, i.e., hybridization, is considered a feasible way to improve composite performance. In this context, this paper presents an experimental work on composites with Kevlar and glass fabrics and a novel thermoset polyurethane matrix. The coupons are manufactured by vacuum infusion technique and low-velocity impact tests are carried out. First, the impact behavior of Kevlar and glass laminates of different thicknesses is assessed, and then impact tests are performed on different configurations of hybrid laminates, both symmetric and non-symmetric. For the non-symmetric specimens, impact tests were conducted on both sides of the stack. Load vs displacement curves are reported along with absorbed energy. To investigate the damage mechanism, the front, back, and cross-section views of the specimens are analyzed, and features related to the stacking sequences are discussed. Thermographic analyses are carried out on the impacted specimens to further analyze damage. The failure mechanisms are different from traditional epoxy composites and a hybridization effect is reported. The results evidence that the hybrid coupons are viable for structural applications, being capable of absorbing high-impact energies, in particular, non-symmetric hybrid laminates outperformed the Kevlar, glass, and symmetric ones, absorbing roughly 15% less energy for the highest energy impact.

The COVID-19 pandemic compelled rapid healthcare adaptations including increased use of telehealth (TH) and virtual care (VC) to provide rehabilitation services. This multi-site cross-sectional survey study examined rehabilitation patients’ and providers’ experiences with service delivery during the COVID-19 pandemic, including the use of TH/VC. Patients and providers who received or provided rehabilitation services were recruited from 1 of 3 large, post-acute rehabilitation systems located in the Southeastern and Midwestern United States during the COVID-19 pandemic. Participants rated personal satisfaction with rehabilitation services received or rendered during the pandemic and willingness to use TH/VC in the future. Questions also addressed accessibility, ease of use, and perceived barriers to TH/VC use. The adoption and personal satisfaction of TH/VC for rehabilitation care varied between patients and providers. Patients reported higher levels of satisfaction compared to providers ( P

Abstract Background Leaf area index (LAI) is a key indicator for the assessment of the canopy’s processes such as net primary production and evapotranspiration. For this reason, the LAI is often used as a key input parameter in ecosystem services’ modeling, which is emerging as a critical tool for steering upcoming urban reforestation strategies. However, LAI field measures are extremely time-consuming and require remarkable economic and human resources. In this context, spectral indices computed using high-resolution multispectral satellite imagery like Sentinel-2 and Landsat 8, may represent a feasible and economic solution for estimating the LAI at the city scale. Nonetheless, as far as we know, only a few studies have assessed the potential of Sentinel-2 and Landsat 8 data doing so in Mediterranean forest ecosystems. To fill such a gap, we assessed the performance of 10 spectral indices derived from Sentinel-2 and Landsat 8 data in estimating the LAI, using field measurements collected with the LI-COR LAI 2200c as a reference. We hypothesized that Sentinel-2 data, owing to their finer spatial and spectral resolution, perform better in estimating vegetation’s structural parameters compared to Landsat 8. Results We found that Landsat 8-derived models have, on average, a slightly better performance, with the best model (the one based on NDVI) showing an R 2 of 0.55 and NRMSE of 14.74%, compared to R 2 of 0.52 and NRMSE of 15.15% showed by the best Sentinel-2 model, which is based on the NBR. All models were affected by spectrum saturation for high LAI values (e.g., above 5). Conclusion In Mediterranean ecosystems, Sentinel-2 and Landsat 8 data produce moderately accurate LAI estimates during the peak of the growing season. Therefore, the uncertainty introduced using satellite-derived LAI in ecosystem services’ assessments should be systematically accounted for.

With the growth of e-commerce, the return policy and become a strategic role in companies establishing relationships with consumers. This study aims to investigate how large Brazilian e-commerce companies seek to form relationships with their consumers through lenient return policies, from the perspective of social exchanges. Therefore, a basic interpretive qualitative study was used, based on the knowledge of nine managers who work in three companies. Data collection was carried out through public documents and semi-structured interviews and the data were submitted to content analysis. The results reveal that retailers' efforts to develop social exchanges with consumers, based on trust, reciprocity and commitment, result in more tolerant return policies. Companies that have the capacity to meet the demand for returns develop practices to increase satisfaction and reduce the risks perceived by the consumer, encouraging trust, and seek to create a reciprocal and committed relationship, which contributes to positive evaluations and repurchase intention. As contributions, this study investigates e-commerce, highlighted on the world stage, and a phenomenon that reflects on the performance of companies, but needs investigation: the return of products. It adds to the management literature, it shows how theory is applied in the return policy and in the relationship between retailer and consumer.

‘I have not found among my possessions anything which I hold more dear than, or value so much as, my knowledge of the actions of great people, acquired by long experience in contemporary affairs, and a continual study of antiquity.’ The Prince, Machiavelli

The development of new natural antibiotics is considered as the heart of several investigations in the nutraceutical field. In this work, leaves of Quercus ilex L. treated by tropospheric ozone (O3) and nitrogen (N) deposition, exhibited a clear antimicrobial efficacy against five multi-drug resistant (MDR) bacterial strains (two gram-positive and three gram-negative). Under controlled conditions, it was studied how simulated N deposition influences the response to O3 and the antibacterial and antioxidant activity, and antioxidant performance. The extraction was performed by ultra-pure acetone using two different steps. A higher antioxidant activity was measured in the presence of interaction between O3 and N treatments on Quercus leaves. At the same time, all organic extracts tested have shown bacteriostatic activity against all the tested strains with a MIC comprised between 9 and 4 micrograms/mL, and a higher antioxidant efficacy shown by spectrophotometric assay. Stronger antimicrobial activity was found in the samples treated with O3, whereas N-treated plants exhibited an intermediate antibacterial performance. This performance is related to the stimulation of the non-enzymatic antioxidant system induced by the oxidative stress, which results in an increase in the production of antimicrobial bioactive compounds.

Se denomina “Deterioro Cognitivo Leve” a un estado transicional entre los cambios cognitivos del envejecimiento normal y un estadio temprano de la demencia. En la actualidad, el constructo deterioro cognitivo leve (DCL) se reconoce como una condición patológica, no como un proceso normal asociado a la edad, y se utiliza específica- mente para referirse a un grupo de individuos que presentan cierto grado de déficit cognitivo cuya severidad resulta insuficiente para cumplir criterios de demencia ya que no presentan un compromiso esencial en las actividades de la vida diaria (1). Originalmente el MCI refería a un déficit de memoria en el contexto de funciones no-amnésicas preservadas (DCL amnésico) pero actualmente el término incluye déficits en otras funciones cognitivas más allá de la memoria. El DCL amnésico es posiblemente un estado precursor de la enfermedad de Alzheimer. Los datos neuropatológicos confirman esta transición del DCL amnésico a enfermedad de Alzheimer.

Donor-recipient (D-R) mismatches outside of human leukocyte antigens (HLAs) contribute to kidney allograft loss, but the mechanisms remain unclear, specifically for intronic mismatches. We quantified non-HLA mismatches at variant-, gene-, and genome-wide scales from single nucleotide polymorphism (SNP) data of D-Rs from 2 well-phenotyped transplant cohorts: Genomics of Chronic Allograft Rejection (GoCAR; n = 385) and Clinical Trials in Organ Transplantation-01/17 (CTOT-01/17; n = 146). Unbiased gene-level screening in GoCAR uncovered the LIMS1 locus as the top-ranked gene where D-R mismatches associated with death-censored graft loss (DCGL). A previously unreported, intronic, LIMS1 haplotype of 30 SNPs independently associated with DCGL in both cohorts. Haplotype mismatches showed a dosage effect, and minor-allele introduction to major-allele-carrying recipients showed greater hazard of DCGL. The LIMS1 haplotype and the previously reported LIMS1 SNP rs893403 are expression quantitative trait loci (eQTL) in immune cells for GCC2 (not LIMS1), which encodes a protein involved in mannose-6-phosphase receptor (M6PR) recycling. Peripheral blood and T cell transcriptome analyses associated the GCC2 gene and LIMS1 SNPs with the TGF-β1/SMAD pathway, suggesting a regulatory effect. In vitro GCC2 modulation impacted M6PR-dependent regulation of active TGF-β1 and downstream signaling in T cells. Together, our data link LIMS1 locus D-R mismatches to DCGL via GCC2 eQTLs that modulate TGF-β1–dependent effects on T cells.

Cities are nowadays facing compelling environmental and climatic challenges that threaten human health and well-being; for this reason, enhancing their sustainability and resilience has rapidly ascended to the top of the global and regional political Agenda. The Urban Green Infrastructure represents a key factor in enhancing the environmental quality of cities, and its planning should be steered by a scientifically-sound operationalisation of the Ecosystem Services concept. In this work, we assess the Ecosystem Services mismatch for air quality regulation in four Italian Municipalities (Milan, Bologna, Rome, and Bari), considering the O3 and PM10 pollution; the study frames a geographical gradient (North-South) and has been conducted on a seasonal basis. We propose a composite-indicatorbased approach for estimating the supply and demand of said Ecosystem Services, including the dimensions of air quality and human health, using both geospatial and tabular data. The spatial and temporal features of mismatch allow distinguishing concerns depending on vegetation quantity (green space areas) and quality (functional diversity), structure of urban settlements and cross-cutting criticalities among cities, and to highlight common indicators of mismatch and priority areas for upcoming interventions.We found that northern cities (Milan and Bologna) suffer a high mismatch, as a result of poor air quality and limited vegetation abundance and functional diversity; southern cities experienced lower demand related to air quality; however, the high mismatch is driven by urban settlement structure and population vulnerability. We also found that compact urbanisation, namely dense urban fabric and the increasing buildings’ height, is linked to a marked mismatch regardless of the city’s dimension and geographical location.We believe such an effort is a fundamental step for translating the Ecosystem Services conceptual framework into the development plans of cities, and thus into concrete actions.Plus, as far as we know, this is one of the first studies explicitly linking urban structure indicators (e.g. building heights and compactness of the urban settlements) to the Ecosystem Services’ mismatch.

IntroductionHypophonia is a common feature of Parkinson’s disease (PD); however, the contribution of motor cortical activity to reduced phonatory scaling in PD is still not clear.MethodsIn this study, we employed a sustained vowel production task during functional magnetic resonance imaging to compare brain activity between individuals with PD and hypophonia and an older healthy control (OHC) group.ResultsWhen comparing vowel production versus rest, the PD group showed fewer regions with significant BOLD activity compared to OHCs. Within the motor cortices, both OHC and PD groups showed bilateral activation of the laryngeal/phonatory area (LPA) of the primary motor cortex as well as activation of the supplementary motor area. The OHC group also recruited additional activity in the bilateral trunk motor area and right dorsal premotor cortex (PMd). A voxel-wise comparison of PD and HC groups showed that activity in right PMd was significantly lower in the PD group compared to OHC (p < 0.001, uncorrected). Right PMd activity was positively correlated with maximum phonation time in the PD group and negatively correlated with perceptual severity ratings of loudness and pitch.DiscussionOur findings suggest that hypoactivation of PMd may be associated with abnormal phonatory control in PD.

Objetivo: Avaliar o perfil de inaptidão sorológica do Serviço de Hemoterapia no período de 2018 a 2022, comparar com a base de dados nacional e levantar os possíveis fatores interferentes. Método: Foi feito um estudo retrospectivo com os dados obtidos através da análise estatística anual do sistema informatizado Hemovida no período de 01/02/2018 a 31/12/2022. Os dados foram comparados com a base de dados Nacional e da região sudeste do Brasil de acordo com o 9º Boletim de Produção Hemoterápica – HEMOPROD 2020. Estes dados foram correlacionados com os registros de validações, não conformidades, registros da captação e da triagem clínica. Resultados: O Hemonúcleo reabriu suas portas em 20/02/2018 após dois anos de interdição para obras, período de treinamentos e ajustes. No período de 20/02/2018 a 31/12/2022 foram testadas 16.342 amostras. A taxa de inaptidão sorológica reduziu de 2018 até 2022 sendo respectivamente, 8,86% (2018), 7,53% (2019), 6,51% (2020), 4,60% (2021) e 4,49% (2022). Como resultado, de 2018 a 2022 houve uma redução de 4,37% na taxa de inaptidão em sorologia e a aptidão acumulada do período foi de 94%. As menores taxas de doenças transmissíveis pelo sangue foram registradas em 2022. Sífilis e Hepatite B (anti-HBc) são as doenças mais prevalentes (2,45% e 1,31%, respectivamente), seguido do HCV (0,35%). As taxas registradas no Brasil através do HEMPROD 2020 no âmbito nacional e do sudeste são respectivamente: Sífilis 1,08% e 1,38%, anti-HBc 1,06% e 1,01%, e anti-HCV 0,22% e 0,19%. As demais doenças infeciosas analisadas: HIV, HTLV, Chagas e Hepatite B (HBsAg) apresentaram taxas menores que as médias nacionais e da região sudeste. Os fatores que contribuíram para a redução das taxas de inaptidão sorológica foram: validação dos tubos de coleta de sangue e treinamento sobre o manuseio dos tubos de coleta; desenvolvimento de trabalho em parceria com a assessoria científica e aprimoramento do desempenho da plataforma de imunoensaio automatizado de quimiluminescência; estruturação do setor de captação de doadores com equipe especializada da enfermagem; treinamento do setor de triagem clínica do doador, trazendo um doador mais consciente sobre a importância das informações prestadas. Conclusão: Após a reabertura do Hemonúcleo observamos que as taxas de inaptidão sorológica do HFSE estão reduzindo progressivamente e encontram-se cada vez mais próximas às taxas de inaptidão nacionais. Podemos concluir que o acompanhamento realizado durante esse período foi de extrema importância na identificação dos aspectos que influenciaram diretamente na redução das taxas de inaptidão sorológica do HFSE e das oportunidades de melhorias.

Neutrophilic inflammation is a hallmark of many monogenic autoinflammatory diseases. Here the authors report a case series of three unrelated boys with perinatal-onset of neutrophilic cutaneous small vessel vasculitis and systemic inflammation, and identify de novo truncating and missense variants in the Src-family tyrosine kinase LYN.

Objetivo: Describir la técnica de bloqueo supramaleolar de tobillo y nuestra experiencia con este bloqueo en la cirugía de tobillo y pie. Materiales y Métodos: Se llevó a cabo un estudio observacional, retrospectivo de los últimos 5 años en pacientes con enfermedad de tobillo y pie, sometidos a un bloqueo supramaleolar de tobillo. Se excluyó a pacientes con cirugía previa, cirugías bilaterales, neuropatía periférica o enfermedad vascular, diabetes, infección activa o tabaquistas. Se realizó el bloqueo supramaleolar de tobillo con lidocaína al 2% y bupivacaína al 0,5%, teniendo en cuenta las referencias anatómicas. Se evaluaron la duración del bloqueo, la escala analógica visual de dolor a las 24 h de la cirugía, el tiempo hasta la toma del primer analgésico y el grado de satisfacción del paciente. Resultados: Se incluyó a 771 pacientes operados, todos tuvieron una analgesia completa por, al menos, 12 h (duración promedio 18 h). El puntaje promedio de la escala para dolor a las 24 h fue de 1,4. El tiempo promedio hasta la toma del primer analgésico fue de 16 h. El grado de satisfacción del paciente con el bloqueo y el dolor percibido en las primeras 24 h fue: muy satisfecho (89%), satisfecho (10%) y poco satisfecho (1%). No hubo casos de secuela neurológica permanente, toxicidad sistémica ni infección. Conclusión: El bloqueo supramaleolar de tobillo es un método simple, eficaz y seguro que puede realizar el traumatólogo para obtener una analgesia posquirúrgica prolongada.

Frailty is a clinically measurable state of vulnerability to developing increased dependency and/or mortality when exposed to a stressor. Chronic diseases, aggressive treatments, antibiotic overuse, microbiota changes, immune senescence, and increased use of medical devices and implants (i.e., central lines and catheters) expose modern patients to healthcare-associated infections (HAIs), multidrug-resistant bacteria, and new and unusual opportunistic pathogens. Older adults are among the main victims of HAIs and are associated with high costs, disability, morbidity, and mortality. Ralstonia pickettii is an emerging opportunistic pathogen that causes rare nosocomial infections in frail individuals. Herein, we present a case of bloodstream infection caused by R. pickettii in an 88-year-old woman with a relatively mild course. In addition to describing this unusual finding, this report discusses the problem of HAIs in older adults. Older age, comorbidities, and hospital admissions were among the main risk factors for HAIs. Adherence to guidelines, training, auditing, and surveillance is crucial for reducing the burden of HAIs in acute settings. Furthermore, avoiding incongruous hospitalizations would have positive implications both for preventing HAIs and improving patient quality of life.

Abstract This study aimed to define the pharmacokinetics (PKs) of oral mannitol used as an osmotic laxative for bowel preparation for colonoscopy. The PKs of oral mannitol was evaluated in a substudy as part of a phase II dose‐finding, international, multicenter, randomized, parallel‐group, endoscopist‐blinded study. Patients were randomly assigned to take 50, 100, or 150 g mannitol. Venous blood samples were drawn at baseline (T0), 1 h (T1), 2 h (T2), 4 h (T4), and 8 h (T8) after completion of mannitol self‐administration. The mean mannitol plasma concentrations (mg/ml) were dose‐dependent with a consistent difference among doses. The mean maximum concentration (Cmax) ± SD was 0.63 ± 0.15, 1.02 ± 0.28, and 1.36 ± 0.39 mg/ml, in the three dosage groups, respectively. The mean area under the curve from zero to infinity (AUC0−∞) was 2.667 ± 0.668, 4.992 ± 1.706, and 7.403 ± 3.472 mg/ml*h in the 50, 100, and 150 g mannitol dose groups, respectively. Bioavailability was similar in the three dose groups and was just over 20% (0.243 ± 0.073, 0.209 ± 0.081, and 0.228 ± 0.093 in the 50, 100, and 150 g mannitol dose groups, respectively). The present study showed that the bioavailability of oral mannitol is just over 20% and is similar for the three tested doses (50, 100, and 150 g). The linear increase in Cmax, AUC0−t8, and AUC0−∞ must be considered when choosing the oral mannitol dose for bowel preparation to avoid its systemic osmotic effects.

Eosinophilic esophagitis (EoE) is a chronic gastrointestinal disorder characterized by food antigen–driven eosinophilic inflammation and hyperproliferation of esophageal mucosa. By utilizing a large-scale, proteomic screen of esophageal biopsies, we aimed to uncover molecular drivers of the disease. Proteomic analysis by liquid chromatography–tandem mass spectrometry identified 402 differentially expressed proteins (DEPs) that correlated with the EoE transcriptome. Immune cell–related proteins were among the most highly upregulated DEPs in EoE compared with controls, whereas proteins linked to epithelial differentiation were primarily downregulated. Notably, in the inflamed esophageal tissue, all 6 subunits of the minichromosome maintenance (MCM) complex, a DNA helicase essential for genomic DNA replication, were significantly upregulated at the gene and protein levels. Furthermore, treating esophageal epithelial cells with a known inhibitor of the MCM complex (ciprofloxacin) blocked esophageal epithelial proliferation. In a murine model of EoE driven by overexpression of IL-13, ciprofloxacin treatment decreased basal zone thickness and reduced dilated intercellular spaces by blocking the transition of epithelial cells through the S-phase of the cell cycle. Collectively, a broad-spectrum proteomic screen has identified the involvement of the MCM complex in EoE and has highlighted MCM inhibitors as potential therapeutic agents for the disease.

Introducción: El objetivo principal de la terapia pulpar es mantener la integridad y salud de los dientes y sus estructuras de soporte. En odontopediatría, el tratamiento de molares primarios diagnosticados con pulpitis irreversible o necrosis pulpar representa uno de los grandes desafíos en la práctica clínica debido a la complejidad de la anatomía radicular, tiempo de trabajo y dificultad para la correcta instrumentación. La técnica “Lesion Sterilization Tissue Repair” (LSTR) busca esterilizar la lesión y reparar tejidos por medio del uso de pastas antibióticas sin la necesidad de instrumentar los canales radiculares. Reporte de caso: Paciente femenina de 9 años que asiste a la consulta odontológica asintomática. En el examen clínico el diente segundo molar primario lado mandibular izquierdo (diente #75) presenta lesión activa y cavitada de caries dental, absceso y movilidad grado I. En la radiografía periapical presenta área radiolúcida en la región de la furca, sugiriendo el diagnóstico de necrosis pulpar. Para el tratamiento pulpar se optó por realizar la técnica LSTR con la pasta CTZ, compuesta por cloranfenicol, tetraciclina, óxido de zinc y eugenol. Posteriormente, el molar fue restaurado con una corona de acero inoxidable. Después de 8 meses, el diente se encuentra asintomático, con la restauración satisfactoria, movilidad fisiológica e integridad gingival; radiográficamente hay ausencia de radiolucidez en la región de la furca y reabsorción ósea patológica. Conclusión: el tratamiento endodóntico en el molar primario con necrosis pulpar utilizando la técnica LSTR con la pasta CTZ presentó excelentes resultados clínicos y radiográficos.

Até o aparecimento da carbenicilina no fim da década de 60, praticamente nenhuma penicilina ou cefalosporina exibia atividade significante contra a Pseudomonas aeruginosa. Nos últimos dez anos, um número cada vez maior de antibióticos B-lactâmicos têm sido isolados; porém no INCa, somente a cefalotina, cefalexina, ampicilina e a carbenicilina estão disponíveis para o uso clínico. O baixo grau de sensibilidade da P. aeruginosa à carbenicilina em nosso hospital e a detecção de micro-epidemia por cepas resistentes à amicacina, o que pode acarretar na transmissão desta tendência às de mais cepas existentes no hospital, levaram-nos a estudar comparativamente a resposta da Pseudomonas aeruginosa, “in vitro", aos antibióticos B-lactâmicos e aos aminoglicosídeos mais utilizados.

O artigo estuda o papel do PMN na defesa do organismo nas infecções por Candida, e o significado da permanência da Candida viva no interior dos neutrófilos.