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.

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.

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.

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.

2-Arylpropionic Acid Pyrazolamides as Cannabinoid CB2 Receptor Inverse Agonists Endowed with Anti-Inflammatory Properties.

Among the most recent proposals regarding the mechanism of action of dipyrone, the modulation of cannabinoid receptors CB1 and CB2 appears to be a promising hypothesis. In this context, the present work describes a series of five novel pyrazolamides (7-11) designed as molecular hybrids of dipyrone metabolites and NSAIDs, such as ibuprofen and flurbiprofen. Target compounds were obtained in good overall yields (50-80%) by classical amide coupling between 4-aminoantipyrine and arylacetic or arylpropionic acids, followed in some cases by N-methylation of the amide group. The compounds presented good physicochemical properties in addition to stability to chemical (pH 2 and 7.4) and enzymatic (plasma esterases) hydrolysis and showed medium to high gastrointestinal and BBB permeabilities in the PAMPA assay. When subjected to functional testing on CB1- or CB2-transfected cells, compounds demonstrated an inverse agonist profile on CB2 receptors and the further characterization of compound LASSBio-2265 (11) revealed moderate binding affinity to CB2 receptor (Ki = 16 µM) with an EC50 = 0.36 µM (Emax = 63%). LASSBio-2265 (11) (at 1, 3, and 10 mg/kg p.o.) was investigated in the formalin test in mice and a remarkable analgesic activity in the late inflammatory phase was observed, suggesting it could be promising for the treatment of pain syndromes associated with chronic inflammatory diseases.

Phenylbenzohydrazides Obtained from Isatoic Anhydride Present Anti-Inflammatory Activity In Vivo and In Vitro.

BACKGROUND: Despite the existence of a wide variety of anti-inflammatory drugs, the vast majority are classified as steroidal or non-steroidal. Both classes present a variety of side effects that limit usage. Thus, the search for new molecules with anti-inflammatory potential is still important. METHODS: Five phenylbenzohydrazides were synthetized and evaluated in pre-clinical models of acute inflammation in vivo and in vitro. RESULTS: The new substances (INL-06, -07, -10, and -11), as well as AISCT, significantly reduced cell migration induced by carrageenan. It was also observed that all INLs inhibited protein extravasation as well as cytokines (IL-6, IL-1ß, and TNF-α) and nitric oxide (NO) production. The INL-11 was demonstrated to be the most potent, since the inhibition observed in several parameters was significant even when compared with dexamethasone. In vitro INLs also reduced cytokines and NO production and inducible nitric oxide (iNOS) enzyme activity. The INL-11 was the most effective in reducing cell migration in vitro. CONCLUSIONS: Our data suggest that these substances are suitable for further development into a new series of compounds that could lead to new hits and future drug prototypes for anti-inflammatory conditions.

Copaiba Oil Resin Exerts an Additive Effect to Babassu Oil on Behavioral Changes in Human Endometriotic Cell Cultures.

BACKGROUND: Current drugs for the treatment of endometriosis are not able to completely cure the condition, and significant side effects hinder the continuation of treatment. Therefore, it is necessary to search for new drug candidates. In the present paper, the use of plant extracts is highlighted. Babassu oil and Copaiba oil resin have several therapeutic properties. We investigated the in vitro effects of two nanoemulsions containing oil extracted from Babassu (Orbignya speciosa) nuts (called SNEDDS-18) and/or oil resin extracted from Copaiba trunk (Copaifera langsdorffii) (called SNEDDS-18/COPA) on cultured human eutopic endometrium stromal cells from endometrial biopsies of patients without (CESC) and with (EuESC) endometriosis as well as human stromal cells from biopsies of endometriotic lesions (EctESC). METHODS: CESC, EuESC, and EctESC were taken and treated with SNEDDS-18 and SNEDDS-18/COPA to evaluate their effects on cytotoxicity, cell morphology, proliferation, and signaling pathways. RESULTS: After 48 h of incubation with SNEDDS-18 and SNEDDS-18/COPA, cell viability and proliferation were inhibited, especially in EctESC. The lowest concentration of both nanoemulsions reduced cell viability and proliferation and broke down the cytoskeleton in EctESCs. After 24 h of treatment a decrease in IL-1, TNF-α, and MCP-1 was observed, as well as an increase in IL-10 production. CONCLUSIONS: Both nanoemulsions can affect endometriotic stromal cell behaviors, thus revealing two potential candidates for new phytotherapeutic agents for the management of endometriosis.