R-954, a bradykinin B1 receptor antagonist, as a potential therapy in a preclinical endometriosis model.

Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues outside of the uterine cavity. Currently available drugs are efficacious in treating endometriosis-related pain, however it's not a targeted treatment. The aim of this work is to evaluate the effects of R-954, a bradykinin B1 receptor antagonist, in a murine model of endometriosis. The model was induced in animals through autologous transplantation of part of the uterine horn. After 51 days, it was observed that implants developed into endometriotic lesions. The administration of R-954 or progesterone, for 15 consecutive days, prevented the progression of cyst development, reduced the size and weight of the cysts. Both treatments also reduced cellular infiltrate and production of inflammatory mediators (interleukin-1ß, interleukin-6, tumor necrosis factor). However, only R-954 decreased angiogenic factors (VEGF and VEGF receptor). In addition, treatment with the antagonist did not interfere in the females' estrous cycle, as well as prevented gestational losses (reduction in the number of intermediate resorptions in pregnant females with endometriosis). Data suggested that R-954 has anti-inflammatory and anti-angiogenic effects; does not influence the estrous cycle; and prevents the number of gestational losses suggesting it as a good candidate for endometriosis treatment.

Intraoperative 3D fluoroscopy accurately predicts final electrode position in deep brain stimulation surgery.

PURPOSE: In the absence of an intraoperative CT or MRI setup, post-implantation confirmation of electrode position in deep brain stimulation (DBS) requires patient transportation to the radiology unit, prolonging surgery time. This project aims to validate intraoperative 3D fluoroscopy (3DF), a widely available tool in Neurosurgical units, as a method to determine final electrode position. METHODS: We performed a retrospective study including 64 patients (124 electrodes) who underwent DBS at our institution. Intraoperative 3DF after electrode implantation and postoperative volumetric CT were acquired. The Euclidean coordinates of the electrode tip displayed in both imaging modalities were determined and inter-method deviations were assessed. Pneumocephalus was quantified and its potential impact in determining the electrode position analyzed. Finally, 3DF and CT-imposed exposure to radiation was compared. RESULTS: The difference between the electrode tip estimated by 3DF and CT was 0.85 ± 0.03 mm, and not significantly different (p = 0.11 for the distance to MCP assessed by both methods), but was, instead, highly correlated (p = 0.91; p < 0.0001). Even though pneumocephalus was larger in 3DF (6.89 ± 1.76 vs 5.18 ± 1.37 mm3 in the CT group, p < 0.001), it was not correlated with the difference in electrode position measured by both techniques (p = 0.17; p = 0.06). Radiation exposure from 3DF is significantly lower than CT (0.36 ± 0.03 vs 2.08 ± 0.05 mSv; p < 0.0001). CONCLUSIONS: Intraoperative 3DF is comparable to CT in determining the final DBS electrode position. Being a method with fewer radiation exposure, less expensive, faster and that avoids patient transportation outside the operation room, it is a valid tool to replace postoperative CT.

Dual transcriptomic analysis reveals early induced Castanea defense-related genes and Phytophthora cinnamomi effectors.

Phytophthora cinnamomi Rands devastates forest species worldwide, causing significant ecological and economic impacts. The European chestnut (Castanea sativa) is susceptible to this hemibiotrophic oomycete, whereas the Asian chestnuts (Castanea crenata and Castanea mollissima) are resistant and have been successfully used as resistance donors in breeding programs. The molecular mechanisms underlying the different disease outcomes among chestnut species are a key foundation for developing science-based control strategies. However, these are still poorly understood. Dual RNA sequencing was performed in C. sativa and C. crenata roots inoculated with P. cinnamomi. The studied time points represent the pathogen's hemibiotrophic lifestyle previously described at the cellular level. Phytophthora cinnamomi expressed several genes related to pathogenicity in both chestnut species, such as cell wall-degrading enzymes, host nutrient uptake transporters, and effectors. However, the expression of effectors related to the modulation of host programmed cell death (elicitins and NLPs) and sporulation-related genes was higher in the susceptible chestnut. After pathogen inoculation, 1,556 and 488 genes were differentially expressed by C. crenata and C. sativa, respectively. The most significant transcriptional changes occur at 2 h after inoculation (hai) in C. sativa and 48 hai in C. crenata. Nevertheless, C. crenata induced more defense-related genes, indicating that the resistant response to P. cinnamomi is controlled by multiple loci, including several pattern recognition receptors, genes involved in the phenylpropanoid, salicylic acid and ethylene/jasmonic acid pathways, and antifungal genes. Importantly, these results validate previously observed cellular responses for C. crenata. Collectively, this study provides a comprehensive time-resolved description of the chestnut-P. cinnamomi dynamic, revealing new insights into susceptible and resistant host responses and important pathogen strategies involved in disease development.

Anti-Inflammatory, Antinociceptive, and LC-MS Metabolic Profile from Pseudotrimezia juncifolia (Klatt) Lovo & A. Gil.

Pseudotrimezia juncifolia (Klatt) Lovo & A. Gil (Iridaceae) is a popularly known species with primarily ornamental economic interest. It has traditional uses as purgative, in conditions related to the menstrual cycle, for blood purification, as wound healing, and as anti-inflammatory. The anti-inflammatory and antinociceptive activities of the decoction from its aerial stems, corms, and stamens are described here with dereplication studies on LC-MS/MS supported by the GNPS platform, where phenolic compounds were annotated and correlated with its biological activity. The decoction was evaluated in chemical (formalin and capsaicin) and thermal (hot plate) induced nociception or carrageenan-induced inflammation in mice. Decoction (at 10, 30, or 100 mg/kg doses) significantly reduced formalin- or capsaicin-induced nociception. All doses also demonstrated an antinociceptive effect in the hot plate model increasing the time the animal spent in responding to thermal signal. Naloxone partially reversed the antinociceptive effect. An anti-inflammatory effect was observed since a reduction in cell migration, protein extravasation interleukin-1, and tumor necrosis factor production induced by carrageenan in the subcutaneous air pouch was quantified. Metabolomic analyses showed a predominance of phenolic substances, mainly flavonoids and chlorogenic acids. The literature showed that these two groups have significant anti-inflammatory and analgesic activity, and chemical data corroborate the pharmacological results observed.

Effects of Euphorbia characias subsp. characias flower extracts on nociceptive pain and acute inflammatory models in mice.

Pain and inflammation are major health issues worldwide, leading to negative consequences. Despite several drugs being available to manage these conditions, their effectiveness can be limited by cost, adverse reactions, and potential tolerance and dependence with long-term use. Euphorbia characias traditionally used in folk medicine for its diverse biological activities - including antiproliferative, antimicrobial, and anti-inflammatory effects - has not been extensively studied in vivo for its analgesic and anti-inflammatory properties. In this study, the antinociceptive and anti-inflammatory properties of the water and ethanolic extracts of E. characias flowers (ECAEFl and ECEEFl) were evaluated using various models. Both extracts significantly reduced paw licking time in a formalin-induced paw licking model, with ECAEFl specifically targeting and ECEEFl affecting both the neurogenic and inflammatory phases. Additionally, in the carrageenan-induced cell migration model, both extracts showed a significant decrease in leukocyte migration, protein extravasation and nitric oxide levels, further demostrating their anti-inflammatory activity. High-Resolution HPLC-ESI-QTOF-MS-MS and HPLC-PDA analysis characterized the chemical composition of the extracts, identifying a significant presence of phenolic compounds, particularly quercetin and its derivatives, which likely contribute to the observed biological activities. These findings highlight the potential of E. characias extracts as natural sources of compounds with antinociceptive and anti-inflammatory properties. Further investigations are needed to elucidate the underlying mechanisms and explore their therapeutic potential in pain and inflammation-related disorders.

Rehabilitation delivery models to foster healthy ageing-a scoping review.

Introduction: Rehabilitation is essential to foster healthy ageing. Older adults have unique rehabilitation needs due to a higher prevalence of non-communicable diseases, higher susceptibility to infectious diseases, injuries, and mental health conditions. However, there is limited understanding of how rehabilitation is delivered to older adults. To address this gap, we conducted a scoping review to describe rehabilitation delivery models used to optimise older adults' functioning/functional ability and foster healthy ageing. Methods: We searched Medline and Embase (January 2015 to May 2022) for primary studies published in English describing approaches to provide rehabilitation to older adults. Three authors screened records for eligibility and extracted data independently and in duplicate. Data synthesis included descriptive quantitative analysis of study and rehabilitation provision characteristics, and qualitative analysis to identify rehabilitation delivery models. Results: Out of 6,933 identified records, 585 articles were assessed for eligibility, and 283 studies with 69,257 participants were included. We identified six rehabilitation delivery models: outpatient (24%), telerehabilitation (22%), home (18.5%), community (16.3%), inpatient (14.6%), and eldercare (4.7%). These models often involved multidisciplinary teams (31.5%) and follow integrated care principles (30.4%). Most studies used a disease-centred approach (59.0%), while studies addressing multimorbidity (6.0%) and prevalent health problems of older adults, such as pain, low hearing, and vision, or incontinence were scarce. The most frequently provided interventions were therapeutic exercises (54.1%), self-management education (40.1%), and assessment of person-centred goals (40%). Other interventions, such as assistive technology (8.1%) and environmental adaptations (7.4%) were infrequent. Conclusions: Focusing on primary studies, this scoping review provides an overview of rehabilitation delivery models that are used to foster healthy ageing and highlights research gaps that require further attention, including a lack of systematic assessment of functioning/functional ability, a predominance of disease-centred rehabilitation, and a scarcity of programmes addressing prevalent issues like pain, hearing/vision loss, fall prevention, incontinence, and sexual dysfunctions. Our research can facilitate evidence-based decision-making and inspire further research and innovation in rehabilitation and healthy ageing. Limitations of our study include reliance on published research to infer practice and not assessing model effectiveness. Future research in the field is needed to expand and validate our findings.

Active learning for left ventricle segmentation in echocardiography.

BACKGROUND AND OBJECTIVE: Training deep learning models for medical image segmentation require large annotated datasets, which can be expensive and time-consuming to create. Active learning is a promising approach to reduce this burden by strategically selecting the most informative samples for segmentation. This study investigates the use of active learning for efficient left ventricle segmentation in echocardiography with sparse expert annotations. METHODS: We adapt and evaluate various sampling techniques, demonstrating their effectiveness in judiciously selecting samples for segmentation. Additionally, we introduce a novel strategy, Optimised Representativeness Sampling, which combines feature-based outliers with the most representative samples to enhance annotation efficiency. RESULTS: Our findings demonstrate a substantial reduction in annotation costs, achieving a remarkable 99% upper bound performance while utilising only 20% of the labelled data. This equates to a reduction of 1680 images needing annotation within our dataset. When applied to a publicly available dataset, our approach yielded a remarkable 70% reduction in required annotation efforts, representing a significant advancement compared to baseline active learning strategies, which achieved only a 50% reduction. Our experiments highlight the nuanced performance of diverse sampling strategies across datasets within the same domain. CONCLUSIONS: The study provides a cost-effective approach to tackle the challenges of limited expert annotations in echocardiography. By introducing a distinct dataset, made publicly available for research purposes, our work contributes to the field's understanding of efficient annotation strategies in medical image segmentation.

Automated mitral inflow Doppler peak velocity measurement using deep learning.

Doppler echocardiography is a widely utilised non-invasive imaging modality for assessing the functionality of heart valves, including the mitral valve. Manual assessments of Doppler traces by clinicians introduce variability, prompting the need for automated solutions. This study introduces an innovative deep learning model for automated detection of peak velocity measurements from mitral inflow Doppler images, independent from Electrocardiogram information. A dataset of Doppler images annotated by multiple expert cardiologists was established, serving as a robust benchmark. The model leverages heatmap regression networks, achieving 96% detection accuracy. The model discrepancy with the expert consensus falls comfortably within the range of inter- and intra-observer variability in measuring Doppler peak velocities. The dataset and models are open-source, fostering further research and clinical application.

Rehabilitation in primary care for an ageing population: a secondary analysis from a scoping review of rehabilitation delivery models.

BACKGROUND: The world population is ageing rapidly. Rehabilitation is one of the most effective health strategies for improving the health and functioning of older persons. An understanding of the current provision of rehabilitation services in primary care (PC) is needed to optimise access to rehabilitation for an ageing population. The objectives of this scoping review are a) to describe how rehabilitation services are currently offered in PC to older persons, and b) to explore age-related differences in the type of rehabilitation services provided. METHODS: We conducted a secondary analysis of a scoping review examining rehabilitation models for older persons, with a focus on PC. Medline and Embase (2015-2022) were searched to identify studies published in English on rehabilitation services for people aged 50 + . Two authors independently screened records and extracted data using the World Health Organization (WHO)'s operational framework, the Primary Health Care Systems (PRIMASYS) approach and the WHO paper on rehabilitation in PC. Data synthesis included quantitative and qualitative analysis. RESULTS: We synthesised data from 96 studies, 88.6% conducted in high-income countries (HICs), with 31,956 participants and identified five models for delivering rehabilitation to older persons in PC: community, home, telerehabilitation, outpatient and eldercare. Nurses, physiotherapists, and occupational therapists were the most common providers, with task-shifting reported in 15.6% of studies. The most common interventions were assessment of functioning, rehabilitation coordination, therapeutic exercise, psychological interventions, and self-management education. Environmental adaptations and assistive technology were rarely reported. CONCLUSIONS: We described how rehabilitation services are currently provided in PC and explored age-related differences in the type of rehabilitation services received. PC can play a key role in assessing functioning and coordinating the rehabilitation process and is also well-placed to deliver rehabilitation interventions. By understanding models of rehabilitation service delivery in PC, stakeholders can work towards developing more comprehensive and accessible services that meet the diverse needs of an ageing population. Our findings, which highlight the role of rehabilitation in healthy ageing, are a valuable resource for informing policy, practice and future research in the context of the United Nations Decade of Healthy Ageing, the Rehab2030 initiative and the recently adopted WHA resolution on strengthening rehabilitation in health systems, but the conclusions can only be applied to HICs and more studies are needed that reflect the reality in low- and middle-income countries.

Hematopoietic colony-stimulating factors in head and neck cancers: Recent advances and therapeutic challenges.

Colony-stimulating factors (CSFs) are key cytokines responsible for the production, maturation, and mobilization of the granulocytic and macrophage lineages from the bone marrow, which have been gaining attention for playing pro- and/or anti-tumorigenic roles in cancer. Head and neck cancers (HNCs) represent a group of heterogeneous neoplasms with high morbidity and mortality worldwide. Treatment for HNCs is still limited even with the advancements in cancer immunotherapy. Novel treatments for patients with recurrent and metastatic HNCs are urgently needed. This article provides an in-depth review of the role of hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), and interleukin-3 (IL-3; also known as multi-CSF) in the HNCs tumor microenvironment. We have reviewed current results from clinical trials using CSFs as adjuvant therapy to treat HNCs patients, and also clinical findings reported to date on the therapeutic application of CSFs toxicities arising from chemoradiotherapy.

Speech Perception in Ménière Disease.

Introduction Ménière disease (MD) affects the inner ear, comprising the cochlea and semicircular canals. Symptoms include severe incapacitating vertigo, nausea, vomit, aural fullness, and sensorineural hearing loss - in which speech discrimination and intelligibility are impaired and can be quantified with speech audiometry. Objective To investigate the influence of the stimuli presentation level in speech audiometry and the quality of life in adults with and without a diagnosis of MD. Method Two groups were formed with nine individuals each - one with and the other without MD. The Speech Recognition Percentage Index was researched with stimuli presented above the self-reported comfort level or 5 dB below the discomfort level. Dizziness Handicap and Tinnitus Handicap Inventories were administered to individuals with tinnitus and vertigo complaints. Results Speech recognition was better in the study group with higher presentation levels, as 75% of the sample improved their performance. The presence of vertigo significantly impacted the quality of life of individuals in the study group. Conclusion Speech recognition improves with higher presentation levels. Also, MD impacts the quality of life, especially regarding limitations caused by vertigo.

Synthesis of cannabidiol-based compounds as ACE2 inhibitors with potential application in the treatment of COVID-19.

Cannabis is a general name for plants of the genus Cannabis. Used as fiber, medicine, drug, for religious, therapeutic, and hedonistic purposes along the millenia, it is mostly known for its psychoactive properties. One of its major constituents, cannabidiol (CBD), a non-psychoactive substance, among many other biological activities, has shown potential as an anti-SARS-CoV-2 drug. In this work, three derivatives and an analogue of CBD were synthesized, and cell viability and antiviral activities were evaluated. None of the compounds showed cytotoxicity up to a maximum concentration of 100 µM and, in contrast, displayed a significant antiviral activity, superior to remdesivir and nafamostat mesylate, with IC50 values ranging from 9.4 to 1.9 µM. In order to search for a possible molecular target, the inhibitory activity of the compounds against ACE2 was investigated, with expressive results (IC50 ranging from 3.96 µM to 0.01 µM).

A visita domiciliária como fator facilitador na adaptação à parentalidade / The home visit as a facilitating factor in the adaptation to parenthood

Enquadramento: A transição para a parentalidade constitui um desafio importante para os Pais, mas também para os enfermeiros de saúde materna e obstétrica que têm o dever de apoiar nestes processos. A visita domiciliária poderá ser um instrumento de cuidar importante nestes cuidados, pois permite avaliar a dinâmica familiar no seu verdadeiro domínio, sendo assim fulcral avaliar a sua efetividade e o seu potencial para dar suporte à construção de novos papeis. Assim, na primeira parte do presente trabalho será efetuada uma reflexão sobre as aprendizagens efetuadas em contexto de estágio e, por sua vez, na segunda parte será descrita a componente investigativa deste percurso formativo. Objetivos: Refletir sobre as competências do enfermeiro especialista em saúde materna e obstétrica adquiridas ao longo da componente de estágio. Na componente investigativa: conhecer qual o impacto da visita domiciliária enquanto instrumento de cuidados no processo de adaptação ao papel parental de ambos os pais. Identificar necessidades/dificuldades manifestadas por ambos os pais durante a visita domiciliaria sensíveis aos cuidados de enfermagem. Metodologia: Estudo de nível I do tipo exploratório-descritivo de natureza qualitativa. Os dados foram recolhidos através de entrevistas realizadas às mães/casais que receberam visita domiciliária do enfermeiro nos últimos 6 meses, que aceitaram participar voluntariamente da entrevista. Resultados: A análise das entrevistas permitiu perceber que as mães atribuem um valor muito elevado às intervenções realizadas durante a visita domiciliária e que as principais dificuldades manifestadas prendem-se com os cuidados ao recém-nascido. Conclusão: Da componente de estágio faz-se um balanço rico e extremamente positivo. Da componente investigativa pode-se inferir que a visita domiciliária à puérpera, recém-nascido e aos casais é determinante no processo de transição e adaptação à parentalidade, tornando-a mais saudável, feliz e harmoniosa, constituindo um domínio rico de oportunidades de intervenção do enfermeiro especialista em saúde materna e obstétrica.

A Capsid Protein Fragment of a Fusagra-like Virus Found in Carica papaya Latex Interacts with the 50S Ribosomal Protein L17.

Papaya sticky disease is caused by the association of a fusagra-like and an umbra-like virus, named papaya meleira virus (PMeV) and papaya meleira virus 2 (PMeV2), respectively. Both viral genomes are encapsidated in particles formed by the PMeV ORF1 product, which has the potential to encode a protein with 1563 amino acids (aa). However, the structural components of the viral capsid are unknown. To characterize the structural proteins of PMeV and PMeV2, virions were purified from Carica papaya latex. SDS-PAGE analysis of purified virus revealed two major proteins of ~40 kDa and ~55 kDa. Amino-terminal sequencing of the ~55 kDa protein and LC-MS/MS of purified virions indicated that this protein starts at aa 263 of the deduced ORF1 product as a result of either degradation or proteolytic processing. A yeast two-hybrid assay was used to identify Arabidopsis proteins interacting with two PMeV ORF1 product fragments (aa 321-670 and 961-1200). The 50S ribosomal protein L17 (AtRPL17) was identified as potentially associated with modulated translation-related proteins. In plant cells, AtRPL17 co-localized and interacted with the PMeV ORF1 fragments. These findings support the hypothesis that the interaction between PMeV/PMeV2 structural proteins and RPL17 is important for virus-host interactions.

Development of an instrument for measuring the work functioning of persons with epilepsy in clinical settings.

OBJECTIVE: To describe the development process of the Work Functioning Assessment for Epilepsy (WOFAE), an instrument recently developed in Brazil for measuring the work functioning of persons with epilepsy (PwE) in clinical settings, and to evaluate to what extent this instrument is in line with existing generic and epilepsy-specific tools used to measure general and work functioning. METHODS: The development process included four phases: the content development, based on a literature review and using the International Classification of Functioning, Disability and Health (ICF) as a reference framework; a preliminary field test, conducted with 20 PwE; an expert consultation, applying the Delphi Method; and the mapping and content comparison of the WOFAE to other five functioning assessments, using the ICF linking rules. RESULTS: The WOFAE containing 46 items structured into eight domains was developed in an evidence-based and participatory process. It is broader in terms of body functions and environmental factors than the other functioning assessments. CONCLUSION: It is a useful tool to guide multidisciplinary interventions, measure clinical progress and assess disability for the granting of social benefits and retirement pensions of PwE. The future phases consist of revision and psychometric analyses of the instrument to ensure its validity and reliability.

The Role of Plant Latex in Virus Biology.

At least 20,000 plant species produce latex, a capacity that appears to have evolved independently on numerous occasions. With a few exceptions, latex is stored under pressure in specialized cells known as laticifers and is exuded upon injury, leading to the assumption that it has a role in securing the plant after mechanical injury. In addition, a defensive effect against insect herbivores and fungal infections has been well established. Latex also appears to have effects on viruses, and laticifers are a hostile environment for virus colonization. Only one example of successful colonization has been reported: papaya meleira virus (PMeV) and papaya meleira virus 2 (PMeV2) in Carica papaya. In this review, a summary of studies that support both the pro- and anti-viral effects of plant latex compounds is provided. The latex components represent a promising natural source for the discovery of new pro- and anti-viral molecules in the fields of agriculture and medicine.

Speech Perception in Ménière Disease

Abstract Introduction Ménière disease (MD) affects the inner ear, comprising the cochlea and semicircular canals. Symptoms include severe incapacitating vertigo, nausea, vomit, aural fullness, and sensorineural hearing loss - in which speech discrimination and intelligibility are impaired and can be quantified with speech audiometry. Objective To investigate the influence of the stimuli presentation level in speech audiometry and the quality of life in adults with and without a diagnosis of MD. Method Two groups were formed with nine individuals each - one with and the other without MD. The Speech Recognition Percentage Index was researched with stimuli presented above the self-reported comfort level or 5 dB below the discomfort level. Dizziness Handicap and Tinnitus Handicap Inventories were administered to individuals with tinnitus and vertigo complaints. Results Speech recognition was better in the study group with higher presentation levels, as 75% of the sample improved their performance. The presence of vertigo significantly impacted the quality of life of individuals in the study group. Conclusion Speech recognition improves with higher presentation levels. Also, MD impacts the quality of life, especially regarding limitations caused by vertigo.

Tibouchina granulosa Leaves Present Anti-Inflammatory Effect.

The ethanol extract (EE) prepared from the leaves of Tibouchina granulosa, and its fraction in ethyl acetate (fEA) were evaluated concerning their capacity to reduce inflammation in different experimental models. fEA was also studied concerning its chemical constituents. EE and fEA were assayed for their anti-inflammatory potential, using formalin-induced licking behavior and carrageenan-induced inflammation into the subcutaneous air pouch (SAP) models. Reduction in polymorphonuclear cells (PMN) activation was performed in freshly isolated PMN. Chromatographic analysis of fEA was performed by HPLC-DAD. Hispiduloside was isolated as the main constituent in fEA, and its quantity was estimated to be 39.3% in fEA. EE (30 mg/kg) significantly reduced the second phase of formalin-induced licking. fEA demonstrated a reduction in leukocyte migration into the SAP. EE and fEA drastically reduced cytokines (TNF-α, IL-1ß, and IFN-γ), nitric oxide (NO) production, in vitro PMN migration induced by C5a and IL-8, and TNF-α and IL-1ß gene expression. Taken together, our data indicate that either ethanol extract or its fEA fraction from leaves of T. granulosa present an anti-inflammatory effect, contributing to the pharmacological and chemical knowledge of this species and confirming the rationale behind its traditional use.