The Regulation of Axon Diameter: From Axonal Circumferential Contractility to Activity-Dependent Axon Swelling

In the adult nervous system axon caliber varies widely amongst different tracts. When considering a given axon, its diameter can further fluctuate in space and time, according to processes including the distribution of organelles and activity-dependent mechanisms. In addition, evidence is emerging supporting that in axons circumferential tension/contractility is present. Axonal diameter is generically regarded as being regulated by neurofilaments. When neurofilaments are absent or low, microtubule-dependent mechanisms can also contribute to the regulation of axon caliber. Despite this knowledge, the fine-tune mechanisms controlling diameter and circumferential tension throughout the lifetime of an axon, remain largely elusive. Recent data supports the role of the actin-spectrin-based membrane periodic skeleton and of non-muscle myosin II in the control of axon diameter. However, the cytoskeletal arrangement that underlies circumferential axonal contraction and expansion is still to be discovered. Here, we discuss in a critical viewpoint the existing knowledge on the regulation of axon diameter, with a specific focus on the possible role played by the axonal actin cytoskeleton.This work from the authors’ group was supported by Prémio Melo e Castro—Santa Casa da Misericórdia de Lisboa; by the Infrastructure for NMR, EM and X-rays for Translational Research (iNEXT); and by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the Norte Portugal Regional Operational Programme (NORTE 2020), Portugal 2020, and by Portuguese funds through FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior in the framework of the project NORTE-01-0145-FEDER-028623. AC and RP-C are funded by Fundação para a Ciência e Tecnologia—FCT (fellowships SFRH/BPD/114912/2016 and SFRH/BD/112112/2015, respectively)

Cancer-related knowledge and health status among cancer survivors in Portugal

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The impact of breast cancer treatments on sleep quality 1 year after cancer diagnosis

Purpose: The increasing number of women living longer with potential side effects of breast cancer treatment highlights the need of a comprehensive assessment of its burden. Therefore, we aimed to quantify the relation between different breast cancer treatments and sleep quality 1 year after diagnosis. Methods: A cohort of 502 newly diagnosed breast cancer patients was prospectively followed. Sleep quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI), at baseline and at the 1-year follow-up. Odds ratios (OR) were computed to quantify the association between patient characteristics and poor sleep quality (PSQI score >5) at baseline, and relative risks (RR) were computed for the association between treatments and the occurrence of poor sleep quality at 1 year. Results A total of 60.2% of the patients had poor sleep quality before breast cancer treatments, especially those with anxiety [OR = 2.86, 95% confidence interval (95%CI) 1.92 to 4.27] or depression (OR = 5.25, 95%CI 2.01 to 13.67). Radiotherapy increased the risk of poor sleep quality at 1 year (RR = 3.71, 95%CI 1.15 to 11.96, for a cumulative dose >50 Gy) and there was a tendency for a higher risk in those submitted to chemotherapy, although not statistically significant. Conclusions Our study shows that sleep disturbances are frequent before cancer treatment and confirms their co-occurrence with other medical conditions, such as anxiety and depression. Different breast cancer treatments increase the risk of impaired sleep quality, therefore contributing to the global disability associated with cancer treatments.FF and ARC have received co-funded by the BFundação para a Ciência e a Tecnologia^ and the POPH/FSE Program (grant numbers SFRH/BD/92630/2013 and SFRH/BD/102181/2014, respectively). Data management activities were supported by the Chair on Pain Medicine of the Faculty of Medicine, University of Porto and by the Grünenthal Foundation – Portugal

Study protocol for a pilot randomised controlled trial evaluating the feasibility and effectiveness of non-pharmacological interventions to recover functionality after a transient ischaemic attack or a minor stroke: the 'Back to Normal' trial

Introduction Transient ischaemic attack (TIA) and minor stroke are frequently assumed as temporary or non-disabling events. However, evidence suggests that these patients can experience relevant impairment and functional disability. Therefore, the present study aims to evaluate the feasibility and effectiveness of a 3-month multidomain intervention programme, composed of five non-pharmacological strategies, aimed at accelerating return to pre-event level of functionality in patients with TIA or minor stroke. Methods and analysis Patients diagnosed with a TIA or a minor stroke are being recruited at the emergency or neurology departments of the Hospital Pedro Hispano, located in Matosinhos, Portugal (n=70). Those who accept to participate will be randomly allocated to two groups (1:1): (a) Intervention-receives a 3 months combined approach, initiating early post-event, composed of cognitive training, physical exercise, nutrition, psychoeducation and assessment/correction of hearing loss; (b) Control-participants will not be subject to any intervention. Both groups will receive the usual standard of care provided to these diseases. Recruitment began in May 2022 and is expected to continue until March 2023. Socio-demographic characteristics, lifestyles, health status, cognitive function, symptoms of anxiety and depression and quality of life will be assessed; as well as anthropometry, blood pressure and physical condition. Time to complete or partial recovery of instrumental activities of daily living will be assessed using an adapted version of the Frenchay Activities Index. All participants will be evaluated before the intervention and after 3 months. Ethics and dissemination This study was approved by the Ethics Committee of the Local Health Unit of Matosinhos (Ref. 75/CES/JAS). Written informed consent will be required from all the participants; data protection and confidentiality will be also ensured. The findings of this project are expected to be submitted for publication in scientific articles, and the main results will be presented at relevant scientific meetings. Trial registration number NCT05369637.This work was financed by national funds through the FCT - Foundation for Science and Technology, I.P., within the scope of projects UIDB/04750/2020 and LA/P/0064/2020. It was also supported by the Portuguese Stroke Society under the research scholarship Prof. Castro Lopes in cerebrovascular disease. The MIND-Matosinhos project was supported by 'Portugal Inovacao Social' and co-funded by the Operational Program Social Inclusion and Employment, Portugal 2020 and European Union, through the European Social Fund (POISE-03-4639-FSE-000793). Funders will not have any influence on the study design, execution, interpretation of data, writing and publication of manuscripts

Roles of the hox proteins in cancer invasion and metastasis

Invasion and metastasis correspond to the foremost cause of cancer-related death, and the molecular networks behind these two processes are extremely complex and dependent on the intra-and extracellular conditions along with the prime of the premetastatic niche. Currently, several studies suggest an association between the levels of HOX genes expression and cancer cell invasion and metastasis, which favour the formation of novel tumour masses. The deregulation of HOX genes by HMGA2/TET1 signalling and the regulatory effect of noncoding RNAs generated by the HOX loci can also promote invasion and metastasis, interfering with the expression of HOX genes or other genes relevant to these processes. In this review, we present five molecular mechanisms of HOX deregulation by which the HOX clusters products may affect invasion and metastatic processes in solid tumours.The work was financed by FEDER (Fundo Europeu de Desenvolvimento Regional) funds through the COMPETE 2020 Operational Programme for Competitiveness and Internationalisa-tion (POCI), Portugal 2020, and by Portuguese funds through FCT (Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior) in the framework of the project POCI-01-0145-FEDER-030562 (PTDC/BTM-TEC/30562/2017). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed

Regular physical activity-related awareness and knowledge in Portugal: results from a population-based survey

Background: Previous studies have shown that adequate physical activity (PA, defined as any bodily movement that requires energy expenditure) related awareness and knowledge is crucial to promote regular PA. Therefore, this study aims to characterize PA awareness and knowledge, and to quantify its association with sociodemographic characteristics, health literacy and frequency of exercise. Methods: In a cross-sectional study conducted in 2012, a total of 1624 Portuguese-speaking residents of mainland Portugal (16–79 years old) were assessed through face-to-face interviews using a structured questionnaire. Adjusted prevalence ratios, calculated using Poisson regression, were used to quantify associations with PA awareness and knowledge. Results: The most reported benefits of PA were “reduces abdominal fat accumulation” (95.8%), “reduces myocardial infarction risk” (92.9%) and “improves bone health” (90.7%), these were less referred by older participants, while more often identified by those who exercise daily. The most referred barrier for people to not practice PA regularly was “lack of time” (33.9%) with differences observed by sex, age, education, employment and health literacy. Over two-thirds of participants correctly identified at least 2 of 3 PAs (“running”, “soccer” and “tennis”) that require the most energy, particularly males, those with higher health literacy and who exercise twice or more times a week. Conclusions: An adequate PA-related awareness and knowledge was observed, and differences according to age, health literacy levels and frequency of exercise were found. As such, awareness-raising interventions to increase regular PA through improving physical literacy and motivation should focus on older adults, those with limited health literacy and who do not exercise.Financial support and sponsorship: This study was supported by FEDER funds through Operational Programme Competitiveness and Internationalization and by national funding from The Portuguese Foundation for Science and Technology – FCT (Portuguese Ministry of Education and Science) within the project (HMSPIISE/SAU-ICT/0004/2009) and the Epidemiology Research Unit – Institute of Public Health, University of Porto (EPIUnit; info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04750/2020/PT). SM was funded under the scope of the project "NEON-PC - Neuro-oncological complications of prostate cancer: longitudinal study of cognitive decline" (POCI-01-0145-FEDER-032358; Ref. PTDC/SAU-EPI/32358/2017). An individual grant attributed to ARC (SFRH/BD/102181/2014) was co-funded by FCT and the “Programa Operacional Capital Humano” (POCH/FSE). The funding sources had no role in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the article for publication

Neuropathic pain induced alterations in the opioidergic modulation of a descending pain facilitatory area of the brain

Opioids play a major role at descending pain modulation but the effects of neuropathic pain on the brain opioidergic system remain understudied. Since descending facilitation is enhanced during neuropathic pain, we studied the opioidergic modulation of the dorsal reticular nucleus (DRt), a medullary pain facilitatory area, in the spared nerve injury (SNI) model of neuropathic pain. We first performed a series of behavioral experiments in naïve-animals to establish the role of µ-opioid receptor (MOR) in the effects of endogenous and exogenous opioids at the DRt. Specifically, we showed that lentiviral-mediated MOR-knockdown at the DRt increased sensitivity to thermal and mechanical stimuli while the MOR agonist DAMGO induced the opposite effects. Additionally, we showed that MOR-knockdown and the pharmacological blockade of MOR by CTAP at the DRt decreased and inhibited, respectively, the analgesic effects of systemic morphine. Then, we performed in vivo microdialysis to measure enkephalin peptides in the DRt and evaluated MOR expression in the DRt at mRNA, protein and phosphorylated form levels by quantitative real-time PCR and immunohistochemistry, respectively. SNI-animals, compared to sham control, showed higher levels of enkephalin peptides, lower MOR-labeled cells without alterations in MOR mRNA levels, and higher phosphorylated MOR-labeled cells. Finally, we performed behavioral studies in SNI animals to determine the potency of systemic morphine and the effects of the pharmacologic and genetic manipulation of MOR at the DRt. We showed a reduced potency of the antiallodynic effects of systemic morphine in SNI-animals compared to the antinociceptive effects in sham animals. Increasing MOR-cells at the DRt of SNI-animals by lentiviral-mediated MOR-overexpression produced no effects on mechanical allodynia. DAMGO induced anti-allodynia only after MOR-overexpression. These results show that MOR inhibits DRt pain facilitatory actions and that this action contributes to the analgesic effects of systemic opioids. We further show that the inhibitory function of MOR is impaired during neuropathic pain. This is likely due to desensitization and degradation of MOR which are adaptations of the receptor that can be triggered by MOR phosphorylation. Skipping counter-regulatory pathways involved in MOR adaptations might restore the opioidergic inhibition at pain facilitatory areas.This work was supported by the FCT (PTCD/SAU-NSC/110954/2009 FEDER/COMPETE) and ESF (NORTE-08-5369-FSE-000026)

The occupational risk of Helicobacter pylori infection: a systematic review

The aim of this systematic review was to describe the prevalence of Helicobacter pylori infection in specific occupational groups and to compare them with the general population. We searched PubMedA (R) to identify original studies reporting the prevalence of H. pylori infection in occupational groups. The differences between occupational groups and the general population were analyzed taking into account the direction and statistical significance of the differences observed when comparing each occupational group with a reference group (either recruited in the same study or using an external comparator). A total of 98 studies addressing the prevalence of H. pylori infection in occupational groups were included in the systematic review. Overall, health professionals showed a significantly higher prevalence of H. pylori infection than the general population, especially among those working at gastrointestinal units. Similar results were found in subjects involved in agricultural, forestry and fishery, as well as in sewage workers, miners, and workers at institutions for the intellectually disabled, although differences were less pronounced. Our results show an occupational risk of H. pylori infection supporting the role of oral-oral, fecal-oral, and zoonotic transmission. Studies comparing specific occupational groups with adequate comparators may contribute to better identify groups at higher risk of infection. The recognition of this infection as an occupational disease would result in early detection and treatment, as well as prevention and control of its transmission in workplaces.This study was funded by FEDER through the Operational Programme Competitiveness and Internationalization and national funding from the Foundation for Science and Technology-FCT (Portuguese Ministry of Science, Technology and Higher Education), under the Unidade de Investigacao em Epidemiologia-Instituto de Saude Publica da Universidade do Porto (EPIUnit) (POCI-01-0145-FEDER-006862; Ref. UID/DTP/04750/2013). Individual PhD Grants attributed to AF (PD/BD/105823/2014), ARC (SFRH/BD/102181/2014) and SM (SFRH/BD/102585/2014), and a Post-Doc Grant attributed to BP (SFRH/BPD/108751/2015) were funded by FCT and the Programa Operacional Capital Humano (POCH/FSE)

Inter-comparison of three-dimensional models of volcanic plumes

We performed an inter-comparison study of three-dimensional models of volcanic plumes. A set of common volcanological input parameters and meteorological conditions were provided for two kinds of eruptions, representing a weak and a strong eruption column. From the different models, we compared the maximum plume height, neutral buoyancy level (where plume density equals that of the atmosphere), and level of maximum radial spreading of the umbrella cloud. We also compared the vertical profiles of eruption column properties, integrated across cross-sections of the plume (integral variables). Although the models use different numerical procedures and treatments of subgrid turbulence and particle dynamics, the inter-comparison shows qualitatively consistent results. In the weak plume case (mass eruption rate 1.5 × 106 kg s− 1), the vertical profiles of plume properties (e.g., vertical velocity, temperature) are similar among models, especially in the buoyant plume region. Variability among the simulated maximum heights is ~ 20%, whereas neutral buoyancy level and level of maximum radial spreading vary by ~ 10%. Time-averaging of the three-dimensional (3D) flow fields indicates an effective entrainment coefficient around 0.1 in the buoyant plume region, with much lower values in the jet region, which is consistent with findings of small-scale laboratory experiments. On the other hand, the strong plume case (mass eruption rate 1.5 × 109 kg s− 1) shows greater variability in the vertical plume profiles predicted by the different models. Our analysis suggests that the unstable flow dynamics in the strong plume enhances differences in the formulation and numerical solution of the models. This is especially evident in the overshooting top of the plume, which extends a significant portion (~ 1/8) of the maximum plume height. Nonetheless, overall variability in the spreading level and neutral buoyancy level is ~ 20%, whereas that of maximum height is ~ 10%. This inter-comparison study has highlighted the different capabilities of 3D volcanic plume models, and identified key features of weak and strong plumes, including the roles of jet stability, entrainment efficiency, and particle non-equilibrium, which deserve future investigation in field, laboratory, and numerical studies.YJS was partially supported by the ERI Cooperative Research Program and KAKENHI (25750142). The computations of SK-3D were carried out in part on the Earth Simulator at the JAMSTEC and also on the Primergy RX200S6 at the Research Computer System, Kyushu University. AC was partially supported by a grant of the International Research Promotion Office Earthquake Research Institute, the University of Tokyo. AC, TEO and MC were partially supported by the EU-funded project MEDiterranean Supersite Volcanoes (MEDSUV; grant no. 308665). MC acknowledges CINECA award N. HP10BKFD9F (2013) for high performance computing resources and support. AVE acknowledges NSF Postdoctoral Fellowship EAR1250029, a U.S. Geological Survey Mendenhall fellowship, and grant GID 61233 from NASA Ames Supercomputing Center

Association of physical activity with physical function and quality of life in people with hip and knee osteoarthritis: longitudinal analysis of a population-based cohort

Hip and knee osteoarthritis (HKOA) is a chronic disease characterized by joint pain that leads to reduced physical function and health-related quality of life (HRQoL). At present, no cure is available. Clinical trials indicate that people with HKOA benefit from physical activity in several health-related outcomes. However, few studies have evaluated the long-term positive effect of regular physical activity. This study analyzed participants with HKOA from a nationwide population-based cohort (EpiDoC Cohort) to assess the impact of physical activity on patients' physical function and HRQoL over a long-term follow-up. The regular weekly frequency of intentional physical activity was self-reported as non-frequent (0 times/week), frequent (1-2 times/week), or very frequent (≥ 3 times/week). This study followed 1086 participants over a mean period of 4.7 ± 3.4 years, during which 6.3% and 14.9% of participants reported frequent and very frequent physical activity, respectively. Using linear mixed models, we found that frequent (β = - 0.101 [- 0.187, - 0.016]; β = 0.039 [- 0.002, 0.080]) and very frequent physical activity (β = - 0.061 [- 0.118, - 0.004]; β = 0.057 [0.029, 0.084]) were associated with improved physical function and HRQoL over time, respectively, when compared with non-frequent exercise, adjusting for years to baseline, sex, age, years of education, body mass index, multimorbidity, hospitalizations, clinical severity, and unmanageable pain levels. These findings raise awareness of the importance of maintaining exercise/physical activity long term to optimize HRQoL and physical function. Further studies must address barriers and facilitators to improve the adoption of regular physical activity among citizens with HKOA.info:eu-repo/semantics/publishedVersio