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ABSTRACT Mycobacterium abscessus (Mab) is an emerging pathogen that poses a severe health threat, especially in people with cystic fibrosis and other chronic lung diseases. Available drugs are largely ineffective due to an exquisite intrinsic resistance, making Mab infections only comparable to multidrug-resistant tuberculosis. Current treatment is based on lengthy multidrug therapy, complicated by poor outcomes and high rates of treatment failure, recurrence, and mortality. Thus, finding new and more efficient drugs to combat this pathogen is urgent. However, drug discovery efforts targeting Mab have been limited, and traditional drug screening methods are labor-intensive, low-throughput, and do not reflect clinical effectiveness. Therefore, this work aimed to develop a new, efficient, and reliable tool for drug screening against Mab that can be used in vitro for identifying hits in a high-throughput manner and in vivo to select drug candidates for future clinical trials. We engineered two stable double-reporter strains of Mab capable of emitting strong fluorescent and luminescent signals. This is due to the expression of mScarlet protein and luciferase enzyme or the entire lux operon. Importantly, these strains maintain the same ground characteristics as the non-transformed Mab strain. We show that these new strains can be applied to various setups, from MIC determination in broth cultures and macrophage infection assays to in vivo infection (using the Galleria mellonella model). Using these strains enhances the potential for high-throughput screening of thousands of compounds in a fast and reliable way.IMPORTANCEMycobacterium abscessus (Mab) is currently considered an “incurable nightmare.” Its intrinsic resistance, high toxicity, long duration, and low cure rates of available therapies often lead to the clinical decision not to treat. Moreover, one of the significant drawbacks of anti-Mab drug development is the lack of correlation between in vitro susceptibility and clinical efficacy. Most drug screening assays are performed on Mab growing in liquid cultures. But being an intracellular pathogen, inducing granulomas and biofilm formation, the broth culture is far from ideal as in vitro drug-testing setup. This study presents new double-reporter Mab strains that allow direct real-time bacterial detection and quantification in a non-invasive way. These strains can be applied to an extensive range of experimental settings, far surpassing the utility of single-reporter bacteria. They can be used in all steps of the pre-clinical anti-Mab drug development pipeline, constituting a highly valuable tool to increase its success.

Introduction: Higher consumption of ultra-processed foods (UPF) had been associated with higher risk of non-communicable diseases (NCD) and NCD-promoting nutrient profile such as high sodium content and low potassium content. The objective of the study was to evaluate the level of food processing according to the NOVA classification and its relationship with sodium and potassium intake estimated by 24-hour urinary excretion. Methods: This is a cross-sectional study. Data collection included 107 workers from a public university (51.4% female; mean age 47 years) participating in an iMC Salt clinical trial). A 24-hour urinary collection was used to estimate sodium and potassium intake, validated by the creatinine coefficient. The corresponding 24-hour dietary recall was used to assess food intake and foods were categorized using the NOVA classification according to the degree and purpose of processing, into four groups. Nutri-score was also used to categorize UPF and provide more information about the nutritional quality of products. Results: The largest energy contribution came from the group of unprocessed or minimally processed foods (51.6%), followed by UPF (24%), processed foods (21.8%) and processed culinary ingredients (2.6%). Individuals with the lowest caloric contribution of the consumption of UPF had higher average values of potassium (K) intake (1438 vs 1136 mg/1000kcal; p=0.007), as individuals with the highest weight contribution of the consumption of unprocessed or minimally processed foods (1434 vs 1109 mg/1000kcal; p=0.010). For sodium (Na) intake no significant results were found between individuals with the lowest and the highest consumption of each NOVA group. Conclusions: Higher consumption of fresh or minimally processed foods and lower UPF intake were associated with higher K intake values. On the other hand, higher UPF intake was not associated with higher Na intake values. Funding: This work was supported by Fundação para a Ciência e Tecnologia by Grant POCI-01-0145-FEDER-029269) and by the European Regional Development Fund (ERDF) through NORTE 2020 (Northern Regional Operational Program 2014/2020) - NORTE-01-0145-FEDER-072687.

Background: Handgrip strength (HGS) is an indicator of muscular strength, used in the diagnosis of sarcopenia, undernutrition, and physical frailty as well as recovery. Typically, the maximum HGS value is used; however, recent evidence suggests the exploration of new indicators provided based on the force–time curve to achieve a more comprehensive assessment of muscle function. Therefore, the objective was to identify indicators of the HGS profile beyond maximum HGS, based on force–time curves, and to systematize knowledge about their applications to various types of samples, health issues, and physical performance. Methods: A systematic review was performed including studies whose participants’ HGS was assessed with a digital or adapted dynamometer. The outcome measures were HGS profile indicators calculated from the force–time curve. Results: a total of 15 studies were included, and the following indicators were identified: grip fatigue, fatigability index, fatigue rate, fatigue resistance, time to 80% maximal voluntary contraction, plateau coefficient of variability, time to maximum value, T-90%, release rate, power factor, grip work, average integrated area, endurance, cycle duration, time between cycles, maximum and minimum force–velocity, rate of grip force, final force, inflection point, integrated area, submaximal control, and response time. Conclusions: Various indicators based on the force–time curve can be assessed through digital or adapted dynamometers. Future research should analyze these indicators to understand their implications for muscle function assessment, to standardize evaluation procedures, to identify clinically relevant measures, and to clarify their implications in clinical practice.

BackgroundWhite matter hyperintensities are lesions of presumed vascular origin associated with Cerebral small vessel disease. WMH are common findings that and are associated with increased risk of cognitive impairment and dementia. A higher prevalence of WMH has been also reported in patients with bipolar disorder (BD), although the evidence is conflicting.ObjectiveTo compare the prevalence of WMH in adults with BD, with the prevalence found in healthy controls.MethodsWe searched the Embase, Medline/PubMed, and references cited in articles retrieved on May 20, 2023. We included case-control studies that compared the prevalence of WMH in adult BD patients with the prevalence of WMH in healthy controls, using T2-weighted magnetic resonance imaging. We performed a meta-analysis using a random-effects method based on the inverse-variance approach.FindingsWe included 22 case-control studies reporting data of 1313 people. The overall rate of WMH was 46.5% in BD patients and 28% in controls (pooled Odds Ratio 2.89, 95% CI 1.76; 4.75). We found a moderate heterogeneity across studies (I2 = 0.49). Publication bias was not significant.InterpretationWe found evidence that BD patients have a higher burden of WMH than healthy controls. Main limitations were impossibility of analyzing gender differences and bipolar type, moderate heterogeneity between studies, non-representative samples, lack of control for major confounders and search in two electronic databases.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023428464

Abstract In recent decades, urban mobility has assumed a need for adaptation due to the more significant congestion experienced in cities and the growing focus on sustainability. Several solutions are proposed to help citizens move around in an urban environment. Most are not yet aware of the universal and accessible aspect that these solutions must have. This paper proposes a route support system embedded in a mobile application, Viana+Acessível, using a multi-objective approach. The application aims to promote accessible mobility within the city, contributing to physical and psychological well-being for citizens with reduced mobility, temporary or permanently, such as people with spectrum autism disorder, the visually impaired, wheelchair users, pregnant, and the elderly. For the evaluation of the algorithms, four objective measures were considered: accessibility, slope, time, and length of the paths. The tests carried out with different routing algorithms showed that the A-Star presented the fastest results in terms of execution time compared to the Dijkstra, Floyd–Warshall, and Bellman–Ford. When analysing in a multi-objective approach, time, slope and accessibility were demonstrated to be conflicting objectives. Bi-objective and tri-objective were applied and Pareto front was explored. Graphical abstract

This study outlines the assessment of the cyber–physical system SPERTA, which was designed to evaluate the real-time performance of Taekwondo athletes. The system conducts performance analyses focusing on speed, acceleration, strength, and identifying and quantifying the athlete’s movements. The research involved administering an online questionnaire to athletes and coaches to evaluate the system’s acceptance and usability. The methodology included using a questionnaire with open and closed questions to assess participant satisfaction and system usability. The results showed a positive response to the system, with participants emphasizing its reliability and ease of use. An analysis of the responses revealed a strong internal consistency, as indicated by the Cronbach’s alpha coefficient, which enhances the research instrument’s reliability. Additionally, the analysis of open-ended questions was conducted through thematic analysis to gain a deeper understanding of participants’ experiences and perceptions of the system. These results highlight the effectiveness of the SPERTA system as a valuable tool for the real-time performance evaluation of Taekwondo athletes, providing insights for future improvements and the development of more effective training techniques.

The Montgomery-Åsberg Depression Rating Scale (MADRS) is considered one of the gold-standard measures to assess depression severity. To standardise the MADRS administration, a structured interview was developed (SIGMA). This study aims to translate and validate the SIGMA for European Portuguese. Twenty patients (80% women) were interviewed by ten dyads of raters (trained clinical psychologists and psychiatrists) using the European Portuguese version of the MADRS and its structured interview SIGMA. There was no significant difference in the total MADRS score between raters (interviewers and observers). The intraclass correlation for the total score between raters using the SIGMA was excellent (r = .98; p < .001). All items had excellent to good item-level intraclass correlation, and the internal consistency by rater role was good. The European Portuguese version of the SIGMA showed good preliminary psychometric properties (reliability and internal consistency). Our results suggest that the SIGMA is a useful and robust interview guide for assessing the ten depression symptoms in the MADRS, regardless of the rater clinical background.

The food industry is looking for substitutes for sucrose in food items due to the excessive consumption of products with added sugar and the demand for healthier products. Alternative natural sweeteners can help achieve this goal. Different types of low-fat yoghurts (1% fat), with low-protein and high-protein levels (3% and 4.5–6.5% protein, respectively), were produced using alternative natural sweeteners. The low-protein yoghurts were made with stevia (0.03% w/w) or agave syrup (4.5% w/w). The high-protein yoghurts were made with stevia (0.04% w/w), xylitol (6% w/w) or honey (6% w/w). Sucrose (6% w/w) was used as a control in both trials. pH and titratable acidity, CIEL*a*b* color parameters, syneresis index, rheology and the texture profile of the low-fat yoghurts were evaluated over refrigerated storage. All products underwent sensory evaluation by an untrained panel. The high-protein yoghurts were found to be more acidic (>1% as lactic acid), had a lower syneresis index (between 2.1 and 16.2%) and a better consistency (stronger gel structure) than the low-protein yoghurts. In terms of rheological parameters, stevia-sweetened yoghurts scored higher than the other sweetened yoghurts, showing a better gel structure. The different sweeteners tested did not significantly affect the sensory properties of the yoghurts, although the high-protein yoghurts scored higher for most of the attributes evaluated. Overall, consumers preferred stevia-sweetened yoghurts to yoghurts sweetened with sucrose or agave for the low-protein yoghurts. Of the tested formulations, those containing high protein with the alternative natural sweetener xylitol received higher scores in all attributes. These results reveal the potential of the tested natural sweeteners as sucrose substitutes, while contributing to improving the nutritional value of yoghurts.

IntroductionOsteopenia has been associated to several inflammatory conditions, including mycobacterial infections. How mycobacteria cause bone loss remains elusive, but direct bone infection may not be required.MethodsGenetically engineered mice and morphometric, transcriptomic, and functional analyses were used. Additionally, inflammatory mediators and bone turnover markers were measured in the serum of healthy controls, individuals with latent tuberculosis and patients with active tuberculosis.Results and discussionWe found that infection with Mycobacterium avium impacts bone turnover by decreasing bone formation and increasing bone resorption, in an IFNγ- and TNFα-dependent manner. IFNγ produced during infection enhanced macrophage TNFα secretion, which in turn increased the production of serum amyloid A (SAA) 3. Saa3 expression was upregulated in the bone of both M. avium- and M. tuberculosis-infected mice and SAA1 and 2 proteins (that share a high homology with murine SAA3 protein) were increased in the serum of patients with active tuberculosis. Furthermore, the increased SAA levels seen in active tuberculosis patients correlated with altered serum bone turnover markers. Additionally, human SAA proteins impaired bone matrix deposition and increased osteoclastogenesis in vitro. Overall, we report a novel crosstalk between the cytokine-SAA network operating in macrophages and bone homeostasis. These findings contribute to a better understanding of the mechanisms of bone loss during infection and open the way to pharmacological intervention. Additionally, our data and disclose SAA proteins as potential biomarkers of bone loss during infection by mycobacteria.

This paper aims to demonstrate how design and digital media can have a relevant contribution to the improvement of Taekwondo athletes’ performance. This study focuses on answering the existing gap of a solution that allows quick and accurate access to data about the performance of martial arts athletes. This access to complex information, previously inaccessible or indecipherable to athletes and coaches, allowed, through digital design, the improvement of communication and a more personalized training feedback. The methodology developed was based on design thinking, in a work process that consisted of user identification, and the conception of a prototype in the user-centred design framework. The results obtained in the usability tests performed with Taekwondo athletes and coaches were demonstrative of the efficiency of the designed solution. These scores are also a stimulus for the potential replication and adaptation of the study in other martial arts.

O Ensino de Química para as pessoas com deficiência visual implica na utilização de materiais didático-pedagógicos e tecnológicos adaptados e/ou especializados e métodos específicos de ensino para eliminar barreiras pedagógicas impostas pela diminuição da acuidade visual a que estão expostos. Neste artigo, apresentamos uma análise panorâmica dos inventários descritivos relativa à construção e utilização de materiais didáticos para o ensino de química a alunos com deficiência visual entre o interstício de 2009 a 2018. Para isso, foram utilizadas as seguintes combinações de palavras descritoras: ensino de química, inclusão escolar, deficiência visual e materiais didáticos. Foram também realizadas consultas em teses, dissertações, periódicos científicos e atas dos anais do Encontro Nacional de Ensino de Química, Encontro Nacional de Pesquisa em Educação em Ciência e Congresso Brasileiro de Química. Os resultados apontaram para o predomínio de uma visão instrumentalista do uso dos materiais como adequados, úteis e que favorecem a aprendizagem sensorialmente tátil. Ressaltamos a necessidade de reflexões mais apuradas para que a funcionalidade desses materiais não se reduza a mero instrumentalismo. Destacamos uma tendência em algumas produções sobre as investigações na construção das imagens mentais, trazendo importantes contribuições para o entendimento da elaboração conceitual a partir da percepção tátil dos materiais utilizados.

RESUMO Neste estudo, considera-se como dimensão política a relação que os trabalhadores estabelecem com a gestão pública em saúde e seus desdobramentos no trabalho na Atenção Básica (AB) nas modalidades de organização da AB. Objetivou-se discutir o conflito entre enfermeiros da AB e gestão municipal em torno da contratualização e recontratualização ao Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (PMAQ-AB) como manifestação da dimensão política. Estudo de caso instrumental e qualitativo, alicerçado na Análise de Discurso de matriz francesa. O corpus constituiu-se por entrevistas semiestruturadas com oito enfermeiros, informantes-chave da AB municipal de Ribeirão Preto (SP), e por documentos de planejamento de cinco quadriênios de gestão. Observa-se uma transição incompleta do modelo de AB, mais como mistura do que de transição, com uma implantação incipiente da Estratégia Saúde da Família. Fica claro que a relação entre enfermeiros e gestão não é de confiança, nem de corresponsabilidade. Não há perspectiva de participação nos processos de decisão relativos ao PMAQ-AB, cuja condução privilegiou os aspectos burocráticos esvaziando a política de avaliação de sentido para os trabalhadores. Apesar de responsabilizarem a gestão, os enfermeiros se limitam a formas de resistência pontuais, em um contexto de ausência de negociação coletiva.

Peritoneal dialysis (PD)-related peritonitis is a frequent complication. PD units should be aware of all possible pathogens and share their experience about prevention and optimal management. Uncommon bacteria, a special group with crescent incidence in PD practice, may require singular considerations. A case of peritonitis due to Ewingella americana, a rare human pathogen, is reported, with a favorable outcome. To date, only three other cases have been described in the literature. New evidence is necessary for a better understanding of this pathogen and its consequences in PD modality.

Regardless of the type of sport, coaches must perform the difficult task of evaluating the performance of athletes. In some cases, this task is aided using technology which provides tools for this purpose. When the sport considered is taekwondo this scenario does not apply as the athlete evaluation methods used are mostly manual. Thus, the project presented in this paper has the main objective to develop a system that can be used as a tool to evaluate the performance of taekwondo athletes in real time, with special attention to the low cost of implementation and ease of use. With the intention of meeting these requirements, the developed system comprises a 3D camera with a depth sensor (Orbbec Astra), Inertial Measurement Units (IMUs) with accelerometer and gyroscope, a computer and specific software developed for this purpose. This system allows the collection of data from the athletes’ movements necessary for the creation of a dataset that is then analyzed and interpretated. The system permits the user to obtain real-time information about the speed, acceleration, and strength of the athlete’s limbs during training as well as the identification of some movements and their accounting. To achieve this functionality, deep-learning architecture models were used, more specifically long short-term memory (LSTM). The intention is to provide a new training methodology through faster feedback, so that a faster evolution of the athlete’s performance is possible, contributing to the technological development of the assessment practices used in taekwondo.

Small ruminant dairy products are common in some Mediterranean countries, in the Middle East and Africa, and can play a particular role in the development of rural areas. Butter has been the object of few research studies aimed at evaluating its potential as a vehicle for probiotic microorganisms. Moreover, the recovery of fermented buttermilk with functional properties can be considered an excellent opportunity to value this dairy byproduct. Therefore, the purpose of the present work was to develop different sheep butters and respective buttermilks after cream fermentation by: (1) a mesophilic aromatic starter (A); (2) a kefir culture (K); and (3) a mixture of probiotic bacteria (P). The butters and buttermilk produced with fermented cream were compared with non-fermented sweet cream (S) butter or buttermilk, respectively, regarding their physicochemical, microbiological and sensory characteristics. The adjusted production (%, w/v) obtained for butter were: S (44.48%), A (36.82%), K (41.23%) and P (43.36%). S, A and K butters had higher solids, fat and ashes contents than P butter. The probiotic butter had a total fat of ca. 75% (w/w), below the legal limits, while all others had fat levels above 81.5%. In all samples, the pH decreased and the acidity increased over 90 days of refrigerated storage. These variations were more evident in the P butter, which agrees with the highest lactic acid bacteria counts found in this sample. Differences in color between samples and due to storage time were also observed. In general, the butter samples tended to become darker and yellower after the 60th day of storage. Texture analysis showed comparable results between samples and greater hardness was observed for the P butter, most probably due to its higher relative saturated fatty acids content (66.46% compared to 62–64% in S, A and K butters). Regarding rheological properties, all butters showed pseudoplastic behavior, but butter P had the lowest consistency index (249 kPa.sn−1). The probiotic butter and the corresponding buttermilk had viable cell counts greater than 7 Log CFU/g, indicating their suitability as probiotic carriers. All products were well accepted by consumers and small, but non-significant, differences (p > 0.05) were observed in relation to the sensory parameters evaluated. In general, it can be concluded that the use of adequate starter cultures can allow the production of innovative and potentially healthier products, alongside the valorization of dairy byproducts, improving the income of small-scale producers.

This work reports the synthesis, structural and thermal analysis, and in vitro evaluation of the antimicrobial activity of two new organic salts (OSs) derived from the antimycobacterial drug clofazimine and the fluoroquinolones ofloxacin or norfloxacin. Organic salts derived from active pharmaceutical ingredients (API-OSs), as those herein disclosed, hold promise as cost-effective formulations with improved features over their parent drugs, thus enabling the mitigation of some of their shortcomings. For instance, in the specific case of clofazimine, its poor solubility severely limits its bioavailability. As compared to clofazimine, the clofazimine-derived OSs now reported have improved solubility and thermostability, without any major deleterious effects on the drug’s bioactivity profile.

ABSTRACT Objectives: to analyze the impact of social protection programs on adults diagnosed with Tuberculosis. Methods: systematic review conducted by PRISMA, with registration PROSPERO CRD42019130884. The studies were identified in the VHL, PubMed, Scielo, CINAHL and Scopus databases, using the descriptors “Social Protection” and “Tuberculosis”, in combination with keywords combined with Boolean operators AND and OR. Observational and interventional studies published until October 23, 2019, in Portuguese, English and Spanish, were included. Results: social protection programs improve the treatment of tuberculosis, cure rates, adherence to treatment, the provision of services for the control of TB and reduce poverty. Conclusions: social protection programs have a positive impact on the treatment and control of people diagnosed with Tuberculosis.

(1) Background: Excessive salt intake is associated with an increased risk of hypertension and cardiovascular disease, so reducing it is critical. The main objective of this study was to verify whether one intervention to reduce added salt during cooking changed knowledge, attitudes and behavior (KAB) towards salt, and to analyze changes in the main sources of salt. (2) Methods: The intervention study was an 8-week randomized controlled trial with 97 workers from a public university. KAB in relation to salt were obtained through the WHO STEPwise questionnaire, and the main sources of salt were obtained by 24-h food recall and 24 h urinary sodium excretion over two days. (3) Results: After the intervention, participants in the intervention group reported a decrease in the addition of salt when cooking (p = 0.037), an increase in the percentage of subjects who avoided the consumption of processed foods (from 54.2% to 83.3%, p = 0.001), who looked for salt on food labels (from 18.8% to 39.6%, p = 0.013), and who bought low-salt food alternatives (from 43.8% to 60.4%, p = 0.039). However, there were no significant differences between the intervention group and the control group at baseline and post-intervention assessments. In the intervention group, after the intervention, the added salt decreased by 5%; food sources of salt such as the snacks and pizza group decreased by 7%, and the meat, fish and eggs group increased by 4%, but without statistical significance. (4) Conclusions: With innovative equipment for dosing salt when cooking, it is possible to change some dimensions of consumer behavior in relation to salt.

Introduction Excessive salt intake is a public health concern due to its deleterious impact on health. Most of the salt consumed come from those that are added when cooking. This study will improve knowledge on the effectiveness of interventions to reduce salt consumption among consumers.Methods and analysis In this randomised clinical trial, we will be evaluating the efficacy of an intervention—the Salt Control H, an innovative prototype equipment to monitor and control use of salt when cooking—among workers from a public university, with the aim of reducing their dietary salt intake. We will randomly select 260 workers who meet the eligibility criteria and who are enrolled to an occupational health appointment and randomise them into one of the two arms of the study (either control or intervention), with matched baseline characteristics (sex and hypertension). The intervention will last for 8 weeks, during which the participants will use the equipment at home to monitor and control their use of salt when cooking. The main outcome will be 24-hour urinary sodium excretion at baseline, at fourth and eighth weeks of intervention, and at 6 months after intervention.Ethics and dissemination Ethical approval for the study has been obtained from the Ethics Committee of the Centro Hospitalar Universitário São João. The results of the investigation will be published in peer-reviewed scientific papers and presented at international conferences.Trial registration number NCT03974477Equipment provisional patent number Registered at INPI: 20191000033265.

Background: This study aims to demonstrate the practical application of an innovative easy-to-use equipment to dosage cooking salt, and evaluate the effectiveness in reducing 30% of the added salt in meals and the impact on consumer’s satisfaction and food waste. Methods: Two canteens from one public university where randomized in one control arm and one intervention arm. The first step was to evaluate the salt added to food through atomic emission spectrophotometry in both canteens, and the second step was to perform gradual reductions of up to 30% of cooking salt in the intervention canteen using the Salt Control-C (SC-C) equipment. Consumer acceptability was assessed through satisfaction questionnaires and food waste was evaluated by weighing. Results: The intervention canteen achieved to a reduction of more than 30% of added salt in soup (−34.3% per 100 g), fish dish (−41.1% per 100 g) and meat dish (−48.0% per 100 g), except for the vegetarian dish (6.1% per 100 g). There was no decrease in consumer satisfaction, with a significant satisfaction increase of 15.7% (p = 0.044) regarding the flavor of the main dish. Also, no significant differences were found in food waste. Conclusions: SC-C seems to be effective in reducing 30% of added salt levels in canteen meals, and may be a good strategy to control and reach adequate levels of added salt in meals served outside-the-home, promoting benefits to the individual’s health.

The increasing resistance of infectious agents to available drugs urges the continuous and rapid development of new and more efficient treatment options. This process, in turn, requires accurate and high-throughput techniques for antimicrobials’ testing. Conventional methods of drug susceptibility testing (DST) are reliable and standardized by competent entities and have been thoroughly applied to a wide range of microorganisms. However, they require much manual work and time, especially in the case of slow-growing organisms, such as mycobacteria. Aiming at a better prediction of the clinical efficacy of new drugs, in vitro infection models have evolved to closely mimic the environment that microorganisms experience inside the host. Automated methods allow in vitro DST on a big scale, and they can integrate models that recreate the interactions that the bacteria establish with host cells in vivo. Nonetheless, they are expensive and require a high level of expertise, which makes them still not applicable to routine laboratory work. In this review, we discuss conventional DST methods and how they should be used as a first screen to select active compounds. We also highlight their limitations and how they can be overcome by more complex and sophisticated in vitro models that reflect the dynamics present in the host during infection. Special attention is given to mycobacteria, which are simultaneously difficult to treat and especially challenging to study in the context of DST.

Large variability in COVID-19 clinical progression urges the need to find the most relevant biomarkers to predict patients’ outcomes. We evaluated iron metabolism and immune response in 303 patients admitted to the main hospital of the northern region of Portugal with variable clinical pictures, from September to November 2020. One hundred and twenty-seven tested positive for SARS-CoV-2 and 176 tested negative. Iron-related laboratory parameters and cytokines were determined in blood samples collected soon after admission. Demographic data, comorbidities and clinical outcomes were recorded. Patients were assigned into five groups according to severity. Serum iron and transferrin levels at admission were lower in COVID-19-positive than in COVID-19-negative patients. The levels of interleukin (IL)-6 and monocyte chemoattractant protein 1 (MCP-1) were increased in COVID-19-positive patients. The lowest serum iron and transferrin levels at diagnosis were associated with the worst outcomes. Iron levels negatively correlated with IL-6 and higher levels of this cytokine were associated with a worse prognosis. Serum ferritin levels at diagnosis were higher in COVID-19-positive than in COVID-19-negative patients. Serum iron is the simplest laboratory test to be implemented as a predictor of disease progression in COVID-19-positive patients.

During infections, the host redistributes iron in order to starve pathogens from this nutrient. Several proteins are involved in iron absorption, transport, and storage. Ferritin is the most important iron storage protein. It is composed of variable proportions of two peptides, the L- and H-ferritins (FTL and FTH). We previously showed that macrophages increase their expression of FTH1 when they are infected in vitro with Mycobacterium avium, without a significant increase in FTL. In this work, we investigated the role of macrophage FTH1 in M. avium infection in vivo. We found that mice deficient in FTH1 in myeloid cells are more resistant to M. avium infection, presenting lower bacterial loads and lower levels of proinflammatory cytokines than wild-type littermates, due to the lower levels of available iron in the tissues. Importantly, we also found that FTH1 produced by myeloid cells in response to infection may be found in circulation and that it plays a key role in iron redistribution. Specifically, in the absence of FTH1 in myeloid cells, increased expression of ferroportin is observed in liver granulomas and increased iron accumulation occurs in hepatocytes. These results highlight the importance of FTH1 expression in myeloid cells for iron redistribution during infection.

Background: Adequate sodium intake is important for lowering blood pressure and thus reducing cardiovascular disease risk and other complications. The aim of this review is to identify recent interventions around the world that have been successful in reducing salt intake. Methods: A search in the PubMed, Web of Science and Scopus databases was performed. We include studies published in the last 10 years; randomized trials, pilot intervention without a control arm or experimental study; adult participants; and interventions that successfully reduced salt intake. Study quality was assessed. Results: We included 21 studies, 16 randomized intervention trials and five nonrandomized intervention studies. Eleven interventions described health and nutritional education, seven interventions described nutritional education plus other interventions, and three studies used salt meters to reduce sodium intake. Conclusion: Health and nutritional education, nutritional education plus other interventions and estimates of salt intake showed success in the reduction of salt consumption. There is no evidence that one type of intervention analyzed is more effective than other in reducing salt consumption, so we must analyze each in which individuals or subpopulations will have the intervention performed and use the most suitable approaches to lead to better results.

(1) Background: Excessive salt consumption is associated with an increased risk of hypertension and cardiovascular disease, and it is essential to reduce it to the level recommended by the World Health Organization (n = 57) used the equipment to monitor and control the use of salt during cooking (Salt Control H) at home for 8 weeks. The primary outcome was 24 h urinary sodium excretion as a proxy of salt intake. Secondary outcomes included changes in 24 h urinary potassium excretion, sodium to potassium ratio (Na:K), and blood pressure. (3) Results: There was a decrease in sodium intake after the intervention but with no statistical significance. When analyzing the results by sex and hypertension status, there was a reduction in sodium (−1009 (−1876 to −142), p = 0.025) and in Na:K ratio (−0.9 (−1.5 to −0.3), p = 0.007) in hypertensive men in the intervention group. (4) Conclusions: Interventions with dosage equipment can be valid approaches in individual salt reduction strategies, especially in hypertensive men.

Prevention and control of hypertension and cerebro-cardiovascular diseases are associated with adequate sodium and potassium intake and adherence to a Mediterranean dietary pattern. The aim of this study was to assess the association between adherence to a Mediterranean diet (MD) and the excretion of sodium and potassium as surrogate measures of intake. This is a cross-sectional analysis as part of a larger study (the iMC SALT randomized controlled trial) among workers of a public university. A food frequency questionnaire was used to assess the adherence to MD, using the alternative Mediterranean diet (aMED) score; sodium and potassium excretions were estimated by 24-h urine collections. Sociodemographic and other lifestyle characteristics were also obtained. The associations between the adherence to MD and Na and K excretion were calculated by logistic regression, adjusting for confounding variables. From the 109 selected participants, seven were excluded considering urine screening and completeness criteria, leaving a final sample of 102 subjects (48% male, average age 47 years). Mean sodium and potassium excretion were 3216 mg/day and 2646 mg/day, respectively. Sodium and potassium excretion were significantly higher in men, but no differences were found according to different levels of MD adherence. In logistic regression analysis, sodium, potassium, and sodium-to-potassium ratio urinary excretion tertiles were not associated with MD adherence (low/moderate versus high), even after adjustment for confounding variables. A high adherence to MD was thus not associated with a different level of sodium and potassium intake.

Despite being considered a public health emergency for the last 25 years, tuberculosis (TB) is still one of the deadliest infectious diseases, responsible for over a million deaths every year. The length and toxicity of available treatments and the increasing emergence of multidrug-resistant strains of Mycobacterium tuberculosis renders standard regimens increasingly inefficient and emphasizes the urgency to develop new approaches that are not only cost- and time-effective but also less toxic. Antimicrobial peptides (AMP) are small cationic and amphipathic molecules that play a vital role in the host immune system by acting as a first barrier against invading pathogens. The broad spectrum of properties that peptides possess make them one of the best possible alternatives for a new “post-antibiotic” era. In this context, research into AMP as potential anti-tubercular agents has been driven by the increasing danger revolving around the emergence of extremely-resistant strains, the innate resistance that mycobacteria possess and the low compliance of patients towards the toxic anti-TB treatments. In this review, we will focus on AMP from various sources, such as animal, non-animal and synthetic, with reported inhibitory activity towards Mycobacterium tuberculosis.

Abstract Background Visceral leishmaniasis is a severe and potentially fatal disease caused by protozoa of the genus Leishmania, transmitted by phlebotomine sandflies. In Europe and the Mediterranean region, L. infantum is the commonest agent of visceral leishmaniasis, causing a wide spectrum of clinical manifestations, including asymptomatic carriage, cutaneous lesions and severe visceral disease. Visceral leishmaniasis is more frequent in immunocompromised individuals and data obtained in experimental models of infection have highlighted the importance of the host immune response, namely the efficient activation of host’s macrophages, in determining infection outcome. Conversely, few studies have addressed a possible contribution of parasite variability to this outcome. Methods In this study, we compared three isolates of L. infantum regarding their capacity to grow in the organs of mice, the way they activate the host’s macrophages and other components of the immune response and also their capacity to cope with host’s antimicrobial mechanisms, namely reactive oxygen and nitrogen species. Results We found that the three parasite strains significantly differed regarding the degree to which they induced nitric oxide synthase (NOS2) and arginase expression in infected macrophages and the pattern of cytokine production they induced in the host, resulting in different degrees of inflammatory response in infected livers. Additionally, the three strains also significantly differed in their in vitro susceptibility to reactive oxygen and nitrogen species. This variability was reflected in the capacity of each strain to persist and proliferate in the organs of wild-type as well as NOS2- and phagocyte oxidase- deficient mice. Conclusions The results obtained in this study show that parasite strain variability is an important determinant of disease outcome in L. infantum visceral leishmaniasis, with relevant implications for studies on host-pathogen interaction and also for leishmanicidal drug development.

The genus Mycobacterium comprises not only the deadliest of bacterial pathogens, Mycobacterium tuberculosis, but several other pathogenic species, including M. avium and M. abscessus. The incidence of infections caused by atypical or nontuberculous mycobacteria (NTM) has been steadily increasing, and is associated with a panoply of diseases, including pulmonary, soft-tissue, or disseminated infections. The treatment for NTM disease is particularly challenging, due to its long duration, to variability in bacterial susceptibility profiles, and to the lack of evidence-based guidelines. Treatment usually consists of a combination of at least three drugs taken from months to years, often leading to severe secondary effects and a high chance of relapse. Therefore, new treatment approaches are clearly needed. In this review, we identify the main limitations of current treatments and discuss different alternatives that have been put forward in recent years, with an emphasis on less conventional therapeutics, such as antimicrobial peptides, bacteriophages, iron chelators, or host-directed therapies. We also review new forms of the use of old drugs, including the repurposing of non-antibacterial molecules and the incorporation of antimicrobials into ionic liquids. We aim to stimulate advancements in testing these therapies in relevant models, in order to provide clinicians and patients with useful new tools with which to treat these devastating diseases.

Cinnamic acids are compounds of natural origin that can be found in many different parts of a wide panoply of plants, where they play the most diverse biological roles, often in a conjugated form. For a long time, this has been driving Medicinal Chemists towards the investigation of the therapeutic potential of natural, semi-synthetic, or fully synthetic cinnamic acid conjugates. These efforts have been steadily disclosing promising drug leads, but a wide chemical space remains that deserves to be further explored. Amongst different reported approaches, the combination or conjugation of cinnamic acids with known drugs has been addressed in an attempt to produce either synergistic or multi-target action. In this connection, the present review will focus on efforts of the past decade regarding conjugation with cinnamic acids as a tool for the rescuing or the repurposing of classical antimalarial drugs, and also on future perspectives in this particular field of research.

Introdução: Desde o Séc. XIX que têm sido descritos quadros psicóticos de início súbito e duração limitada. Tendo sido a ‘Bouffée Délirante’ o primeiro quadro a ser descrito, ao longo da história da Psiquiatria várias foram as entidades nosológicas que, entretanto, surgiram nas diferentes escolas: Psicose Ciclóide, Psicose Psicogénica, Psicose Atípica, entre outros. Objetivos: Neste artigo, a propósito de um caso clínico, os autores propõem-se realizar uma revisão dos conceitos históricos das Perturbações Psicóticas Agudas e Transitórias. Métodos: Descrição de um caso clínico e revisão da literatura. Resultados: Caso clínico de um doente de 44 anos com quadro psicótico de início agudo e curta duração, com remissão completa em três dias e retorno ao seu nível de funcionamento habitual. Discussão/Conclusão: Apesar das divergências entre as diferentes concepções teóricas que se mantiveram durante décadas como entidades independentes, actualmente, esses conceitos encontram-se reunidos na 10ª edição da Classificação Internacional de Doenças (CID-10) sob a denominação de Perturbações Psicóticas Agudas e Transitórias. Embora estas classificações não incluam todas as características clínicas inicialmente descritas, procurando o estabelecimento de critérios diagnósticos mais específicos, existe ainda uma percentagem significativa de doentes nos quais o diagnóstico é revisto para uma doença mental crónica.

ABSTRACT Mycobacterial infections cause a significant burden of disease and death worldwide. Their treatment is long, toxic, costly, and increasingly prone to failure due to bacterial resistance to currently available antibiotics. New therapeutic options are thus clearly needed. Antimicrobial peptides represent an important source of new antimicrobial molecules, both for their direct activity and for their immunomodulatory potential. We have previously reported that a short version of the bovine antimicrobial peptide lactoferricin with amino acids 17 to 30 (LFcin17–30), along with its variants obtained by specific amino acid substitutions, killed Mycobacterium avium in broth culture. In the present work, those peptides were tested against M. avium living inside its natural host cell, the macrophage. We found that the peptides increased the antimicrobial action of the conventional antibiotic ethambutol inside macrophages. Moreover, the d-enantiomer of the lactoferricin peptide (d-LFcin17–30) was more stable and induced significant killing of intracellular mycobacteria by itself. Interestingly, d-LFcin17–30 did not localize to M. avium-harboring phagosomes but induced the production of proinflammatory cytokines and increased the formation of lysosomes and autophagosome-like vesicles. These results lead us to conclude that d-LFcin17–30 primes macrophages for intracellular microbial digestion through phagosomal maturation and/or autophagy, culminating in mycobacterial killing. IMPORTANCE The genus Mycobacterium comprises several pathogenic species, including M. tuberculosis, M. leprae, M. avium, etc. Infections caused by these bacteria are particularly difficult to treat due to their intrinsic impermeability, low growth rate, and intracellular localization. Antimicrobial peptides are increasingly acknowledged as potential treatment tools, as they have a high spectrum of activity, low tendency to induce bacterial resistance, and immunomodulatory properties. In this study, we show that peptides derived from bovine lactoferricin (LFcin) improve the antimicrobial activity of ethambutol against Mycobacterium avium growing inside macrophages. Moreover, the d-enantiomer of a short version of lactoferricin containing amino acids 17 to 30 (d-LFcin17–30) causes intramacrophagic death of M. avium by increasing the formation of lysosomes and autophagosomes. This work opens the way to the use of lactoferricin-derived peptides to treat infections caused by mycobacteria and highlights important modulatory effects of d-FLcin17–30 on macrophages, which may be useful under other conditions in which macrophage activation is needed.

El objetivo de este estudio cualitativo fue comprender la percepción de las enfermeras sobre la supervisión de actividades realizadas en las consultas de vacunación de las unidades de atención primaria de salud. Las consultas seleccionadas formaron parte de un estudio preliminar con abordaje cuantitativo, que analizó las mejores consultas de vacunación de la Macrorregión Oeste de Minas Gerais, Brasil, y de las cuales 12 consultas obtuvieron 100% de los criterios estructurales. Fueron entrevistados los enfermeros responsables de estas consultas, y los datos obtenidos fueron sometidos a un análisis temático de contenido. Los resultados demostraron que hay ausencia de un proceso de supervisión enfermera y que tal vez, eso ocurra por la cantidad de acciones asumidas por estos profesionales. El enfermero debe tener una actitud pro-activa con acciones educativas y un acompañamiento más efectivo de las actividades en consulta de vacunación, con el fin de evitar la ocurrencia de fallos en los procedimientos, los cuales pueden tener un impacto en la calidad de los preparados imunobiológicos disponibles para la población.

Estudio de abordaje cuantitativo que objetiva caracterizar los casos de homicidio registrados en el municipalidad de Teresina-PI, en el periodo de 2003 a 2007. La pesquisa fue realizada desde los certificados de fallecimientos (1.084) registrados en el Instituto Médico Legal- IML y el estudio demostró una discrepancia entre los datos obtenidos directamente de estos registros los datos presentados por DATASUS, con valores más altos en todos los años, los primeros datos. Los datos apuntaran una frecuencia mayor entre los hombres (93,3%), adultos jóvenes (44,9%), solteros (72,5%) y estudiantes (19,3%) y especialmente a las víctimas de arma de fuego (52,7%). Por otra parte, el estudio mostró una disminución en el número de homicidios que se produjeron después de la introducción de medidas de seguridad, qué puede venir cimentar discusiones y auxiliar en la reflexión, de la problemática abordada. Así, los profesionales de salud pueden asumir una postura de influenciador a través de medidas de prevención.

The treatment of infectious diseases is increasingly prone to failure due to the rapid spread of antibiotic-resistant pathogens. Antimicrobial peptides (AMPs) are natural components of the innate immune system of most living organisms. Their capacity to kill microbes through multiple mechanisms makes the development of bacterial resistance less likely. Additionally, AMPs have important immunomodulatory effects, which critically contribute to their role in host defense. In this paper, we review the most recent evidence for the importance of AMPs in host defense against intracellular pathogens, particularly intra-macrophagic pathogens, such as mycobacteria. Cathelicidins and defensins are reviewed in more detail, due to the abundance of studies on these molecules. The cell-intrinsic as well as the systemic immune-related effects of the different AMPs are discussed. In the face of the strong potential emerging from the reviewed studies, the prospects for future use of AMPs as part of the therapeutic armamentarium against infectious diseases are presented.

Important for both host and pathogen survivals, iron is a key factor in determining the outcome of an infectious process. Iron with-holding, including sequestration inside tissue macrophages, is considered an important strategy to fight infection. However, for intra-macrophagic pathogens, such as Mycobacterium avium, host defence may depend on intracellular iron sequestration mechanisms. Ferritin, the major intracellular iron storage protein, plays a critical role in this process. In the current study, we studied ferritin expression in mouse bone marrow-derived macrophages upon infection with M. avium. We found that H-ferritin is selectively increased in infected macrophages, through an up-regulation of gene transcription. This increase was mediated by the engagement of Toll like receptor-2, and was independent of TNF-alpha or nitric oxide production. The formation of H-rich ferritin proteins and the consequent iron sequestration may be an important part of the panoply of antimicrobial mechanisms of macrophages.

Partindo do princípio de que o Pacto pela Saúde precisa fazer sentido para quem o efetiva nos espaços micropolíticos, este estudo buscou compreender a implementação do mesmo na prática cotidiana dos trabalhadores de saúde vinculados à coordenação da rede de Atenção Primária à Saúde e à equipe saúde da família do município de Marília (SP). Utilizaram-se a abordagem qualitativa, entrevistas semiestruturadas e análise de conteúdo. Surgiu, nas entrevistas, o modo como as relações entre trabalho e gestão são produzidas e a maneira como as prioridades nacionais se relacionam com essa produção. Buscou-se trazer o reflexo e a contribuição da prática cotidiana à implementação do Pacto pela Saúde.

This was a cross-sectional, observational study conducted in an outpatient specialty district health unit in the city of Ribeirão Preto, in the southeastern Brazilian state of São Paulo, with the aim to analyze the job satisfaction of the nursing staff. Data were collected using the Index of Work Satisfaction (IWS), a validated instrument which was applied to 23 members of the nursing team in January 2012. Among the components of job satisfaction, participants considered Interaction to be most important, followed by Professional Status, Job Requirements, Organizational Policies, Remuneration and Autonomy. The combined mean Index of Work Satisfaction obtained was 8.29, corresponding to poor job satisfaction among the studied population, as most of the studies in the literature that used the same instrument had scores between 12 and 37.