Emerging Roles of tRNAs in RNA Virus Infections.

Viruses rely on the host cell translation machinery for efficient synthesis of their own proteins. Emerging evidence highlights different roles for host transfer RNAs (tRNAs) in the process of virus replication. For instance, different RNA viruses manipulate host tRNA pools to favor viral protein translation. Interestingly, specific host tRNAs are used as reverse transcription primers and are packaged into retroviral virions. Recent data also demonstrate the formation of tRNA-derived fragments (tRFs) upon infection to facilitate viral replication. Here, we comprehensively discuss how RNA viruses exploit distinct aspects of the host tRNA biology for their benefit. In light of the recent advances in the field, we propose that host tRNA-related pathways and mechanisms represent promising cellular targets for the development of novel antiviral strategies.

Vertical integration in healthcare: What does literature say about improvements on quality, access, efficiency, and costs containment?

INTRODUCTION: Vertical integration models involve integrating services from different levels of care (e.g., primary care, acute care, post-acute care). Therefore, one of their main objectives is to increase continuity of care, potentially improving outcomes like efficiency, quality, and access or even enabling cost containment. OBJECTIVES: This study conducts a literature review and aims at contributing to the contentious discussion regarding the effects of vertical integration reforms in terms of efficiency, costs containment, quality, and access. METHODS: We performed a systematic search of the literature published until February 2020. The articles respecting the conceptual framework were included in an exhaustive analysis to study the impact of vertical integration on costs, prices of care, efficiency, quality, and access. RESULTS: A sample of 64 papers resulted from the screening process. The impact of vertical integration on costs and prices of care appears to be negative. Decreases in technical efficiency upon vertical integration are practically out of the question. Nevertheless, there is no substantial inclination to visualise a positive influence. The same happens with the quality of care. Regarding access, the lack of available articles on this outcome limits conjectures. CONCLUSIONS: In summary, it is not clear yet whether vertically integrated healthcare providers positively impact the overall delivery care system. Nevertheless, the recent growing trend in the number of studies suggests a promising future on the analysis of this topic.

Bedside clinical tests to assess sensitization in office workers with chronic neck pain.

OBJECTIVE: This study aimed to assess pain sensitization in individual office workers with chronic neck pain through simple bedside quantitative sensory tests (QST) and to associate the findings with pain intensity and pain catastrophizing. METHODS: One hundred-and-four office workers with chronic neck pain were assessed using pressure pain threshold (PPT) considering pain sensitive if PPTs were lower than 155 kPa in the upper trapezius and 245 kPa in the tibialis anterior. Pain sensitive to temporal summation of pain (TSP) was considered if there was a difference of two points in the visual analogue scale (VAS) comparing the first and last stimulus. Pain sensitive was considered to conditioned pain modulation (CPM) if the CPM-effect was less than -7.5%. Pain intensity and catastrophizing were measured using VAS and with the Pain Catastrophizing Scale. RESULTS: There was at least one pain sensitive QST finding in 66 office workers (63.5%). TSP findings were the most common (48.1%), followed by PPT's (31.7%) and CPM (20.2%). Based on the QST findings, office workers were divided based on the number of individual QST findings, and higher pain intensity and pain catastrophizing scores were found in office workers with one (N = 38, P < 0.05) or two (N = 28, P < 0.05) compared with office workers with no QST findings (N = 38). CONCLUSION: This study demonstrated that most office workers with chronic neck pain exhibit either widespread pressure hyperalgesia, facilitated TSP or impaired CPM, indicating pain sensitization within the central nervous system. This was associated with increased clinical pain and pain catastrophizing rumination scores.

Effectiveness of lip repositioning surgeries in the treatment of excessive gingival display: A systematic review and meta-analysis.

To synthesize the available evidence regarding lip repositioning surgery (LRS) and quantify the short- and long-term reduction in excessive gingival display (EGD) with the procedure. Additionally, evaluate the effect of myotomy on the results. Seven electronic databases were searched up to May 2020 by two independent reviewers. Studies evaluating the exclusive use of LRS to treat EGD were included. After risk of bias assessment, the data were quantitatively evaluated with random-effects meta-analysis. The initial database search yielded 368 studies, of which 16 were selected for full-text review. Finally, eight studies were included. The random effects model exhibited an EGD reduction of 2.87 mm (95% CI: 1.91-3.82) after 3 months of LRS. These results decreased after 6 months (2.71 mm; 95% CI: 1.95-3.47) and 12 months (2.10 mm; 95% CI: 1.48-2.72). Meta-analysis comparing the performance of myotomy showed greater EGD reduction at 6 months than without myotomy (P < 0.02). LRS is an effective approach for treating EGD, and it has satisfactory results up to 6 months. After this period, the effectiveness appears to progressively decrease over time indicating substantial relapse at 12 months. Myotomy seems a suitable alternative to increase the stability of LRS. Lip repositioning surgery is an effective procedure to improve smile esthetics in the short-term (up to 6 months). After this period, the efficacy of LRS seems to decrease progressively, and an approximately 25% relapse may be expected after 12 months. Clinicians should combine the procedure with other approaches, such as plastic periodontal surgeries, restorative procedures, or botulin toxin injections for more predictable and stable outcomes.

Pressure pain thresholds in office workers with chronic neck pain: A systematic review and meta-analysis.

OBJECTIVES: The purpose of this study was to (a) compare pressure pain threshold (PPT) values between office workers with chronic neck pain and asymptomatic controls; (b) establish reference PPT values in chronic neck pain; and (c) evaluate associations between PPTs and pain intensity, and disability. METHODS: Seven English/Portuguese databases were searched for relevant literature. Studies investigating adult office workers (age >18 years) with chronic neck pain were included if PPTs were an outcome. The risk of bias was assessed using the Downs and Black checklist. Meta-analysis was conducted if a cluster contained at least two studies reporting the same PPTs. RESULTS: Ten high quality, two low quality, and one poor quality studies were included. The meta-analysis revealed decreased PPT values in the upper trapezius, extensor carpi ulnaris, and tibialis anterior in office workers with chronic neck pain when compared with healthy workers, without a statistical difference (p > 0.05). The PPT reference value in the upper trapezius was 263 kPa (95% confidence interval [CI] = 236.35 to 289.70), and 365 kPa (95% CI = 316.66 to 415.12) for the tibialis anterior in office workers with chronic neck pain. No correlations were found between the upper trapezius PPT and pain intensity and disability. CONCLUSION: This meta-analysis found that all the PPT measurements were not significantly reduced in office workers with chronic neck pain compared with healthy workers. These assumptions were based on a small sample of existing studies, and therefore further studies are necessary to quantify the differences in PPTs. Hypersensitivity PPT reference values are proposed for localized and extrasegmental sites in office workers with chronic neck pain.

Projected impact of the Portuguese sugar-sweetened beverage tax on obesity incidence across different age groups: A modelling study.

BACKGROUND: Excessive consumption of sugar has a well-established link with obesity. Preliminary results show that a tax levied on sugar-sweetened beverages (SSBs) by the Portuguese government in 2017 led to a drop in sales and reformulation of these products. This study models the impact the market changes triggered by the tax levied on SSBs had on obesity incidence across various age groups in Portugal. METHODS AND FINDINGS: We performed a national market analysis and population-wide modelling study using market data for the years 2014-2018 from the Portuguese Association of Non-Alcoholic Drinks (GlobalData and Nielsen Consumer Panel), dietary data from a national survey (IAN-AF 2015-2016), and obesity incidence data from several cohort studies. Dietary energy density from SSBs was calculated by dividing the energy content (kcal/gram) of all SSBs by the total food consumption (in grams). We used the potential impact fraction (PIF) equation to model the projected impact of the tax-triggered change in sugar consumption on obesity incidence, through both volume reduction and reformulation. Results showed a reduction of 6.6 million litres of SSBs sold per year. Product reformulation led to a decrease in the average energy density of SSBs by 3.1 kcal/100 ml. This is estimated to have prevented around 40-78 cases of obesity per year between 2016 and 2018, with the biggest projected impact observed in adolescents 10 to <18 years old. The model shows that the implementation of this tax allowed for a 4 to 8 times larger projected impact against obesity than would be achieved though reformulation alone. The main limitation of this study is that the model we used includes data from various sources, which can result in biases-despite our efforts to mitigate them-related to the methodological differences between these sources. CONCLUSIONS: The tax triggered both a reduction in demand and product reformulation. These, together, can reduce obesity levels among frequent consumers of SSBs. Such taxation is an effective population-wide intervention. Reformulation alone, without the decrease in sales, would have had a far smaller effect on obesity incidence in the Portuguese population.

Modelling impacts of food industry co-regulation on noncommunicable disease mortality, Portugal.

OBJECTIVE: To model the reduction in premature deaths attributed to noncommunicable diseases if targets for reformulation of processed food agreed between the Portuguese health ministry and the food industry were met. METHODS: The 2015 co-regulation agreement sets voluntary targets for reducing sugar, salt and trans-fatty acids in a range of products by 2021. We obtained government data on dietary intake in 2015-2016 and on population structure and deaths from four major noncommunicable diseases over 1990-2016. We used the Preventable Risk Integrated ModEl tool to estimate the deaths averted if reformulation targets were met in full. We projected future trends in noncommunicable disease deaths using regression modelling and assessed whether Portugal was on track to reduce baseline premature deaths from noncommunicable diseases in the year 2010 by 25% by 2025, and by 30% before 2030. FINDINGS: If reformulation targets were met, we projected reductions in intake in 2015-2016 for salt from 7.6 g/day to 7.1 g/day; in total energy from 1911 kcal/day to 1897 kcal/day due to reduced sugar intake; and in total fat (% total energy) from 30.4% to 30.3% due to reduced trans-fat intake. This consumption profile would result in 248 fewer premature noncommunicable disease deaths (95% CI: 178 to 318) in 2016. We projected that full implementation of the industry agreement would reduce the risk of premature death from 11.0% in 2016 to 10.7% by 2021. CONCLUSION: The co-regulation agreement could save lives and reduce the risk of premature death in Portugal. Nevertheless, the projected impact on mortality was insufficient to meet international targets.

The health care reform in Portugal: Outcomes from both the New Public Management and the economic crisis.

The Portuguese health system concentrates most of its activity in a National Health Service, created in 1979 to promote universal and general access. The National Health Service should ensure equity, efficiency, and quality of all health care delivered services. This study assesses the impact of health care policies between 2002 and 2017, focusing on 3 timeframes: the adoption and adaptation of New Public Management principles to the health care sector (2002 to 2010), the economic and financial crisis period (2011-2015), and the postcrisis recovery period (2016-2017). The current study evaluates the main policy measures in the health sector, presenting their impacts in terms of access, efficiency, accountability, and costs over those 3 economic periods. It was verified that not all the measures implemented by the successive governments obtained the desired outcomes, generating even costs increase, apart from the austerity period in which health expenditure showed a significant reduction because of the financial constraints.

Technical efficiency of Portuguese public hospitals: A comparative analysis across the five regions of Portugal.

The present study aims to analyse the efficiency scores of hospital units, with reference to the five Portuguese health administrative regions (North, Centre, Lisbon and Tagus Valley, Alentejo, and Algarve). This paper contextualizes the process of decentralization of health in Portugal (started 1993) as well as the hospitals' corporatization and merging reforms (started 2002). These reforms aimed to meet health care needs by optimizing costs, improving efficiency, and broadening both access and quality in health services. Data envelopment analysis was used to quantify and compare the efficiencies of 27 hospitals heterogeneously distributed by five administrative regions. The results show a large average performance across the country. However, there are regions with scores larger than the national average and others with inferior results. This interregional diversity points towards disparities that deserve special attention from the policymakers and hospital managers.

Reforms in the Portuguese health care sector: Challenges and proposals.

Portugal has one of the most complete public systems worldwide. Since 1979, the Portuguese National Health Service (NHS) was developed based on the integration and complementarity between different levels of care (primary, secondary, continued, and palliative care). However, in 2009, the absence of economic growth and the increased foreign debt led the country to a severe economic slowdown, reducing the public funding and weakening the decentralized model of health care administration. During the austerity period, political attention has focused primarily on reducing health care costs and consolidating the efficiency and sustainability with no structural reform. After the postcrisis period (since 2016), the recovery of the public health system begun. Since then, some proposals have required a reform of the health sector's governance structure based on the promotion of access, quality, and efficiency. This study presents several key issues involved in the current postcrisis reform of the Portuguese NHS response structure to citizens' needs. The article also discusses the implications of this Portuguese experience based on current reforms with impact on the future of citizens' health.

The Relationship Between Muscular Strength and Dance Injuries: A Systematic Review.

BACKGROUND: The physical demands placed on dancers put them at significant risk for injury, with rates similar to ones sustained by athletes in sports at the same level of performance. Muscle strength has been suggested to play a preventative role against injury in dancers. OBJECTIVE: To systematically search and examine the available evidence on the protective role of muscle strength in dance injuries. METHODS: Five electronic databases and two dance-specific science publications were screened up to September 2015. Study selection was based on a priori inclusion criteria on the relation between muscle strength components and injuries. Methodologic quality and level of evidence were assessed using the Downs and Black (DB) checklist and the Oxford Centre of Evidence-Based Medicine (OCEBM) 2011 model. RESULTS: From 186 titles found, only 8 studies met the inclusion criteria and were considered for review. Because of the significant heterogeneity of the included studies, meta-analysis was deemed inappropriate. The DB quality assessment results ranged from 18.7% to 75% (mean 42.3±16.9) and the OCEBM between 2b and 4. Some level 2b evidence from 2 studies suggested that pre-professional ballet dancers who get injured exhibit lower overall muscle strength scores on the lower extremity, and that lower extremity power gains may be associated with decreased bodily pain but not injury rate. CONCLUSIONS: Although there might be an association trend toward low muscle strength and dance injuries, the nature of that relation remains unclear, and presently the state of knowledge does not provide a solid basis for designing interventions for prevention.

Influenza A virus propagation requires the activation of the unfolded protein response and the accumulation of insoluble protein aggregates.

Influenza A virus (IAV) employs multiple strategies to manipulate cellular mechanisms and support proper virion formation and propagation. In this study, we performed a detailed analysis of the interplay between IAV and the host cells' proteostasis throughout the entire infectious cycle. We reveal that IAV infection activates the inositol requiring enzyme 1 (IRE1) branch of the unfolded protein response, and that this activation is important for an efficient infection. We further observed the accumulation of virus-induced insoluble protein aggregates, containing both viral and host proteins, associated with a dysregulation of the host cell RNA metabolism. Our data indicate that this accumulation is important for IAV propagation and favors the final steps of the infection cycle, more specifically the virion assembly. These findings reveal additional mechanisms by which IAV disrupts host proteostasis and uncovers new cellular targets that can be explored for the development of host-directed antiviral strategies.

The Portuguese NHS 2024 reform: transformation through vertical integration.

Vertical integration models aim for the integration of services from different levels of care (e.g., primary, and secondary care) with the objective of increasing coordination and continuity of care as well as improving efficiency, quality, and access outcomes. This paper provides a view of the Portuguese National Health Service (NHS) healthcare providers' vertical integration, operationalized by the Portuguese NHS Executive Board during 2023 and 2024. This paper also aims to contribute to the discussion regarding the opportunities and constraints posed by public healthcare organizations vertical integration reforms. The Portuguese NHS operationalized the development and generalization of Local Health Units management model throughout the country. The same institutions are now responsible for both the primary care and the hospital care provided by public services in each geographic area, in an integrated manner. This 2024 reform also changed the NHS organic and organizational structures, opening paths to streamline the continuum of care. However, it will be important to ensure adequate monitoring and support, with the participation of healthcare services as well as community structures and other stakeholders, to promote an effective integration of care.

The hidden RNA code: implications of the RNA epitranscriptome in the context of viral infections.

Emerging evidence highlights the multifaceted roles of the RNA epitranscriptome during viral infections. By modulating the modification landscape of viral and host RNAs, viruses enhance their propagation and elude host surveillance mechanisms. Here, we discuss how specific RNA modifications, in either host or viral RNA molecules, impact the virus-life cycle and host antiviral responses, highlighting the potential of targeting the RNA epitranscriptome for novel antiviral therapies.

Association between Musculoskeletal Injuries and Depressive Symptoms among Athletes: A Systematic Review.

Musculoskeletal (MSK) injuries have a significant physical and psychological influence on an athlete's life. A systematic review of prospective cohort, cross-sectional, and case-control studies was undertaken in this study to analyze the association between MSK injuries with depressive symptoms in athletes. We searched on PubMed, Web of Science, and Scopus, with data inception to 15 February 2023. The methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Of the 3677 potential studies only nine were included. These studies showed a bidirectional association between MSK injuries and depressive symptoms. Athletes with MSK injuries had higher levels of depressive symptoms, which raises the likelihood of experiencing depression in the future. Women athletes had higher levels of depressive symptoms compared with men. The presence of depressive symptoms is a significant predictor of disability in athletes. Our findings suggest that coaches should be more aware of depressive symptoms, in order to prevent MSK injuries, and to monitor athletes following an MSK injury.

A Critical Analysis of Decentralizing the Portuguese Public Healthcare Provision Services.

The Portuguese health system has a universal, public, general National Health Service (NHS), tending towards free healthcare access. Created in 1979, this delivery model developed from the integration and complementarity between the different response levels (primary, hospital, continuing, and palliative care). However, over the last 40 years, the initially centralized system underwent a decentralization process with the creation of Regional Health Administrations in the five mainland administrative regions. Since then, the entire NHS has settled around this new organization. The most recent step started in 2018 with the decentralization of primary healthcare skills to 190 municipalities. This paper presents the various critical issues involved in the latest gradual decentralization process in health, intending to bring services closer to the citizens, and to be more focused on their needs. The article identifies and discusses the implications of this experience based on the steps foreseen in the already-published legal texts.

Surgical sterilization of free-ranging capybaras (Hydrochoerus hydrochaeris): "Passos Nunes" uterine horn ligature.

Capybaras are the primary hosts of Amblyomma sculptum tick, vectors of Rickettsia rickettsia bacteria, and the zoonotic agent of Brazilian Spotted Fever (BSF). In this context, contraceptive methods have been suggested for population control in order to reduce the number of free-ranging capybaras cohabiting with humans in urban and rural areas and acting as disease amplifiers. To maintain the group's expected behavior and social hierarchy, sterilization techniques that preserve the gonads are recommended. On 126 female capybaras in the Brazilian state of São Paulo, a new surgical technique named "Passos Nunes" uterine horn ligature was performed after adequate general anesthesia. It achieved effective surgical sterilization, with an incision length of about 3 cm in the periumbilical linea alba, cranial to the pubis. After entering the abdominal cavity, the urinary bladder is pulled laterally to access the uterine horns and the cervix. The uterine horn is folded up, forming a strap; the distal portion of the strap is ligated and its distal end sectioned. The exact process is performed on the opposite horn. After the surgical procedure, the musculature is sutured in a sultan pattern and the subcutaneous tissue with a horizontal mattress pattern. The skin is sutured in a separate simple format, using nylon 2.0 for all steps. The wide exposure of the uterine horns facilitates the confirmation of pregnancy, allowing the surgeon to choose between salpingo hysterectomy or ligature of the uterine horns. The present study presents a new technique of surgical sterilization that can be used in female free-ranging mammals in which maintenance of the gonads is recommended, and births of offspring should not occur.

Modeling the health impact of legislation to limit the salt content of bread in Portugal: A macro simulation study.

Background: Excessive salt consumption-associated with a range of adverse health outcomes-is very high in Portugal, and bread is the second largest source. Current Portuguese legislation sets a maximum limit of 1.4 g salt per 100 g bread, but imported and traditional breads are exempted. In 2017 the Ministry of Health proposed reducing the salt threshold to 1.0/100 g by 2022, however the legislation was vetoed by the European Commission on free-trade grounds. Aims: To estimate the health impact of subjecting imported and traditional breads to the current 1.4 g threshold, and to model the potential health impact of implementing the proposed 1.0 g threshold. Methods: We gathered bread sales, salt consumption, and epidemiological data from robust publicly available data sources. We used the open source WHO PRIME modeling tool to estimate the number of salt-related deaths that would have been averted in 2016 (the latest year for which all data were available) from; (1) Extending the 1.4 g threshold to all types of bread, and (2) Applying the 1.0 g threshold to all bread sold in Portugal. We used Monte Carlo simulations to generate confidence intervals. Results: Applying the current 1.4 g threshold to imported and traditional bread would have averted 107 deaths in 2016 (95% CI: 43-172). Lowering the current threshold from 1.4 to 1.0 g and applying it to all bread products would reduce daily salt consumption by 3.6 tons per day, saving an estimated 286 lives a year (95% CI: 123-454). Conclusions: Salt is an important risk factor in Portugal and bread is a major source. Lowering maximum permissible levels and removing exemptions would save lives. The European Commission should revisit its decision on the basis of this new evidence.

Sensitization in office workers with chronic neck pain in different pain conditions and intensities.

OBJECTIVES: Office workers with chronic neck pain demonstrates signs of widespread hyperalgesia, less efficient descending pain modulation, which could indicate sensitization of central pain pathways. No studies have assessed a wide variety of office workers with different chronic neck pain disorders and assessed the impact of pain intensity on assessments of central pain pathways. This study aimed to assessed pressure pain thresholds (PPTs), temporal summation of pain (TSP) and conditioned pain modulation (CPM) and to associate these with pain intensity and disability in subgroups of office workers. METHODS: One hundred-and-seventy-one office workers were distributed into groups of asymptomatic and chronic neck pain subjects. Chronic neck pain was categorized as chronic trapezius myalgia and chronic non-specific neck pain and as 'mild-pain' (Visual Analog Scale [VAS]≤3) and 'moderate-pain' (VAS>3) groups. PPTs, TSP, CPM, and Copenhagen Psychosocial Questionnaire II were assessed in all subjects. Neck Disability Index and Pain Catastrophizing Scale were assessed in all the symptomatic office workers. RESULTS: PPTs were lower in moderate pain (n=49) and chronic trapezius myalgia (n=56) compared with asymptomatic subjects (n=62, p<0.05). TSP was facilitated in moderate pain group compared with mild pain (n=60, p<0.0001) group and asymptomatic subjects (p<0.0001). No differences were found in CPM comparing the different groups (p<0.05). Multiple regression analysis identified Neck Disability Index and TSP as independent factors for prediction of pain intensity in chronic trapezius myalgia (R2=0.319) and chronic non-specific neck pain (R2=0.208). Somatic stress, stress and sleep as independent factors in chronic non-specific neck pain (R2=0.525), and stress in moderate pain group (R2=0.494) for the prediction of disability. CONCLUSIONS: Office workers with chronic trapezius myalgia and moderate pain intensity showed significant signs of widespread pressure hyperalgesia. Moreover, the moderate pain group demonstrated facilitated TSP indicating sensitization of central pain pathways. Neck Disability Index and TSP were independent predictors for pain intensity in pain groups. Sleep and stress were independent predictors for disability.

Nutri-Score: The Most Efficient Front-of-Pack Nutrition Label to Inform Portuguese Consumers on the Nutritional Quality of Foods and Help Them Identify Healthier Options in Purchasing Situations.

Several studies have identified Front-of-Pack Nutrition Labels (FoPLs) as a promising strategy to improve the nutritional quality of consumers' food choices and encourage manufacturers to offer healthier products. This study aims to fill the evidence gap regarding the most effective FoPL among the Portuguese population. In total, 1059 Portuguese participants were recruited through a web panel provider and asked to declare their intended food choices and to rank three sets of products (pizza, cakes and breakfast cereals) according to their nutritional quality, first in the absence of any labelling, and then with a FoPL displayed on-pack (five FoPLs tested). Finally, participants were asked to answer nine statements related to perceptions of FoPLs. Results showed that participants improved their food choices, depending on the FoPL and the food category. All FoPLs led to a higher percentage of correct responses on the ranking task compared to the no label condition. The Nutri-Score was among the FoPLs producing the greatest improvement across all food categories compared to the reference intakes (OR = 6.45 [4.43-9.39], p-value < 0.0001) and facilitating the highest percentage to correctly rank products according to nutritional quality. This study suggests that, among the available options, Nutri-Score is the most efficient FoPL to inform Portuguese consumers of the nutritional quality of foods and help them identify healthier options in mock purchasing situations.