Spatiotemporal bioavailability of PCDD/Fs and dl-PCBs in wild mussels from the Portuguese Atlantic coast.

This study aimed to assess the spatiotemporal bioavailability of polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs) and dioxin-like polychlorinated biphenyls (dl-PCBs) in wild adult mussels, Mytilus galloprovincialis, collected along the Portuguese Atlantic coast between 2009 and 2020. The work is part of a national environmental monitoring program. The purpose was to evaluate the dioxins' temporal trends, the human and ecological risks, and the correlation between mussels' location and the main pollutant sources in Portugal. The levels and congener patterns of the most toxicity-relevant 17 PCDD/Fs and 12 dl-PCBs were determined, with the dl-PCBs dominant. The sum of Σ17PCDD/Fs and Σ12dl-PCBs values ranged from 2.0 to 4.0 ng WHO-TEQ kg-1, (wet weight basis), below the limits established by the European Commission for contamination in fish and fishery products (6.5 ng per kg-1). The study included five years - 2009, 2010, 2016, 2018 and 2020 -, allowing to verify the impact of European Directive 2013/39/UE against the pollution of water in Portugal; it was observed that dioxin levels in mussels diminished over the time. Statistical analysis allowed verification of different spatial trends of dl-PCB profiles along the Portuguese Atlantic coast. The mono-ortho dl-PCB pentachlorinated congener IUPAC #118 prevailed in 2009 and 2018 in all sampling sites, and it was predominant in 2010, 2016 and 2020, followed by the congeners IUPAC #105, #156 and #167. The IUPAC #167, #169 and #123 were the most abundant hexachlorinated congeners, and the IUPAC #77 the most abundant tetrachlorinated congener. This work emphasises the importance of monitoring dioxins and mapping the congeners in Atlantic coastal ecosystems, to contribute to their elimination.

Predicting hospital emergency department visits accurately: A systematic review.

OBJECTIVES: The emergency department (ED) is a very important healthcare entrance point, known for its challenging organisation and management due to demand unpredictability. An accurate forecast system of ED visits is crucial to the implementation of better management strategies that optimise resources utilization, reduce costs and improve public confidence. The aim of this review is to investigate the different factors that affect the ED visits forecasting outcomes, in particular the predictive variables and type of models applied. METHODS: A systematic search was conducted in PubMed, Web of Science and Scopus. The review methodology followed the PRISMA statement guidelines. RESULTS: Seven studies were selected, all exploring predictive models to forecast ED daily visits for general care. MAPE and RMAE were used to measure models' accuracy. All models displayed good accuracy, with errors below 10%. CONCLUSIONS: Model selection and accuracy was found to be particularly sensitive to the ED dimension. While ARIMA-based and other linear models have good performance for short-time forecast, some machine learning methods proved to be more stable when forecasting multiple horizons. The inclusion of exogenous variables was found to be advantageous only in bigger EDs.

Identifying obesity and COVID-19 overlapping risk-factors: Protocol for a systematic review and meta-analysis.

This systematic review main goal is to identify the common risk factors of obesity and COVID-19 overall, and highlight the ones related to urban settings specifically, using a syndemic framework. COVID-19 highlighted the interaction between infectious diseases and non-communicable diseases. We hypothesise that obesity and COVID-19 share determinants, thus our main goal is to identify the overlapping risk factors and their magnitude of association with both health outcomes. Literature search was conducted in Medline and Embase, Cochrane Library and Epistemonikos, Web of Science and Scopus, ASSIA and SocINDEX and, Google Scholar, in June 2021. Covidence will be used to conduct the title and abstract, and full-text screening, considering the following inclusion criteria: (a) study addresses both health outcomes, (b) full-length articles, (c) study focuses on humans and (d) studies in English. The exclusion criteria will be: (a) study addresses one of the outcomes in combination with other pathologies, (b) not full-length article, (c) study focuses on animals, (d) study not written in English, (e) study focuses on treatment (pharmacological or other), testing (prognostic) or specific patients with other pathologies and (f) study focussed in clinical and/or physiological mechanisms associated with obesity and/or COVID-19. The included studies will be assessed for quality using the Effective Public Health Practice Project for quantitative studies and the tool described by Hawker for qualitative studies. Qualitative results will be assessed using thematic analysis methods to synthesise findings and presented in summary tables. Quantitative results - meta-analysis - will be analysed and presented using Q test and Funnel Plot.

Innovative, Sugar-Free Oral Hydrogel as a Co-administrative Vehicle for Pediatrics: a Strategy to Enhance Patient Compliance.

Palatability and swallowability in the pediatric population are perceived as true challenges in the oral administration of medication. Pediatric patients have high sensitivity to taste and reduced ability to take solid dosage forms, which can often lead to a poor therapeutic compliance. It is crucial to find new strategies to simplify the oral administration of drugs to children. The present paper reports the development of a new hydrogel vehicle adapted to the pediatric population. Several polymers with similar properties were selected and adjustments were made to obtain the desired characteristics of the final product. The developed formulations were studied for organoleptic properties, rheology, mucoadhesion properties, preservative efficacy, and stability. Physical and chemical compatibilities between the vehicle and several drugs/medicines, at the time of administration, were also studied. Six final formulations with different polymers, odor, and color were chosen, and no known interactions with medications were observed. The proposed new oral vehicles are the first sugar-free vehicle hydrogels designed to make the intake of oral solid forms a more pleasant and safer experience for pediatric patients.

Ultrasound-Guided Pulsed Radiofrequency Treatment for Meralgia Paresthetica.

Meralgia paresthetica (MP) is one of the most common mononeuropathies of the lower limb, characterized by injury or compression of the lateral cutaneous femoral nerve at the level of the anterior superior iliac spine and inguinal ligament. Many predisposing factors, such as weight gain, obesity, and restrictive clothing, contribute to the injury of the lateral cutaneous femoral nerve along its course from the pelvis towards the thigh. Although a great number of cases are successfully treated with conservative measures, a subgroup of patients suffer chronic dysesthetic pain with intermittent flare-ups in their lifetime, with a negative impact on quality of life, requiring additional treatment. The purpose of this case report is to describe the successful management of MP with ultrasound-guided pulsed radiofrequency of the lateral cutaneous femoral nerve.

Predictors of Medical Students' Views toward Research: Insights from a Cross-Cultural Study among Portuguese-Speaking Countries.

Developing the skills and interest in scientific research of medical students is crucial to ensuring effective healthcare systems. As such, in this study, we aimed to assess Portuguese-speaking medical students' attitudes and perceptions toward scientific research and clinical practice, and how they are influenced by individual characteristics and regional indicators. A total of 455 first-year students from three medical schools in three countries (Portugal, Brazil, and Angola) participated in this study by completing a questionnaire. Portuguese students attributed the most importance to scientific skills and were the most confident in their ability to perform these skills. Angolan students were the most motivated to perform research and integrate it into the curriculum, despite having the most negative attitudes and perceiving themselves as having less ability to perform scientific skills. Brazilian students had the least positive attitudes toward science. In Portugal, attitudes depended on gross domestic product (GDP), while in Angola, they were influenced by the type of secondary school attendance. Portuguese students' perceptions of scientific skills were related to sex, GDP, type of secondary school, and participation in research. In Brazilian and Angolan students, perceptions were associated with age and research participation, respectively. The findings support the need to promote skills and positive attitudes toward scientific research in future physicians, fostering physician-scientists and improving patient care.

Municipal health promotion programs: is childhood obesity a concern at local level in Portugal?

Health promotion programs, targeted at distinct health outcomes such as childhood obesity, at local level are increasingly used worldwide. Therefore, there is a need to better understand the role of local governments (municipalities) as key public health promoters namely in the prevention of obesity in children. We aimed to provide some input regarding this issue in Portugal. First, we identified health-enhancing programs promoted by Portuguese municipalities in which children could participate. Then, we conducted a document analysis to provide clues about how municipalities conceptualized child health by retrieving information on which topics the programs were focused in, or acted upon, and identifying which socio-ecological model levels were addressed (or not) by each program. The 77 identified programs were promoted by 30 of the 308 Portuguese municipalities and only 11 programs addressed childhood obesity. Most programs focused in the individual health determinants and provided limited information which disabled its deeper analysis. Portuguese municipalities seem to disregard their potential as public health promoters. Childhood obesity is a major public health concern at national (and global) level but the same does not emerge locally. Municipalities are the closest government entities to the population, and it is their responsibility to ensure the population's quality of life, by addressing the social determinants and the physical environments. Therefore, municipalities should acknowledge health in their actions and delineate health improvement programs considering current evidence, specifically in the case of childhood obesity prevention that besides being a health problem in itself, is a risk factor for non-communicable diseases.

Health promotion programs at local level are increasingly used worldwide, specifically targeted at tackling childhood obesity. Thus, local governments (municipalities) become key public health promoters and play an important role in the prevention of obesity in children. We identified health-enhancing programs promoted by Portuguese municipalities in which children could participate. The 77 identified programs were promoted by 30 of the 308 Portuguese municipalities and only 11 programs addressed childhood obesity. It appears that a large number of Portuguese municipalities disregard their potential as public health promoters. Despite the clear governmental concern about childhood obesity at national level, the same does not emerge locally. Municipalities' are responsible for ensuring the population's quality of life, namely through multisectoral actions, which is particularly relevant in the prevention of childhood obesity. Therefore, all municipalities should include childhood obesity prevention in their concerns.

Portuguese Medical Students' Interest for Science and Research Declines after Freshman Year.

The integration of scientific research into medical curricula remains insufficient despite its advantages for medical students' professional development and the advancement of medicine. This study aimed to evaluate the impact of first-year medical course attendance on medical students' attitudes and perceptions towards scientific research and clinical practice, while also assessing the contribution of sociodemographic and academic factors. Two hundred and thirteen medical students self-administrated a questionnaire at the beginning and at the end of the first school year. Their responses were compared and two regression models were calculated to assess factors influencing students' attitudes and perceptions. After freshman year, students displayed significantly lower positive attitudes towards science and research. Their motivation to perform research and to integrate it into the curriculum also decreased, while the importance attributed to research skills for clinical practice increased. Motivation to perform research and negative attitudes were positively and negatively associated with grade point average (GPA), respectively. Female students and those who attended public secondary schools attributed greater importance to communication skills. This study reinforces the need to early develop research skills and positive attitudes in medical students, motivating them to become physician-scientists. Additional follow-up studies may offer further contributions to the integration of research into medical curricula.

The economic crisis impact on the body mass index of children living in distinct urban environments.

OBJECTIVES: Little is known about the impact of the 2008 global economic recession on childhood obesity in Portugal. Thus, this study's goals were to compare weight status of children during and after the economic crisis according to their neighbourhood environment features and to assess changes in specific dietary habits during the economic crisis. STUDY DESIGN: Cross-sectional study. METHODS: Data including weight, height, residence address to allow its geocoding and dietary habits changes during the crisis from children living in Lisbon municipality were collected in 2009 (N = 929) and in 2016 (N = 1751). A multidimensional environment index, with data of both built and socioeconomic nature collected at the statistical section level (areas comprised 300 dwellers) in the 2011 census, was used to characterize neighbourhoods. RESULTS: Overall, the proportion of children who are overweight or obese living in the socioeconomically vulnerable areas decreased in 2016. Families living in the latter areas stopped buying some food items, started to buy cheaper food items, cooked more meals at home and ate less in restaurants. In 2016, the risk for overweight and obesity increased in children who lived in the least advantageous areas. Living in areas with high socioeconomic status or most advantageous areas no longer represented a decreased risk of being overweight or obese in children in 2016 as it did in 2009. CONCLUSIONS: This study suggests that the economic crisis enhanced the social inequalities regarding childhood obesity. These results aid the development of evidence-based strategies to lessen the social inequities in health outcomes created by the crisis.

General anesthesia for emergency cesarean delivery: simulation-based evaluation of residents.

INTRODUCTION: Decreased rates of General Anesthesia (GA) for Cesarean Section (C-section) create a learning problem for anesthesia trainees. In this context, training the management of GA for C-section using simulation techniques allows a safe environment for exposure, learning, performance improvement, and capability retention. OBJECTIVE: Analyze anesthesia residents' performance regarding a simulated clinical case of GA for emergency C-section and identify specific deficits in skill acquisition. METHODS: Between 2015 and 2018, we evaluated the performance of 25 anesthesiology residents challenged by a simulated clinical case of GA for emergency C-section after the conclusion of the obstetric anesthesia rotation. Each resident performed the clinical case once followed by the assessment of their performance. Final scores were given according to the completion rate of 14-tasks, going from 0% to 100%. Two study groups were considered according to residency year for subsequent comparison of results (Group 1, second and third residency years and Group 2, fourth and fifth residency years). RESULTS AND DISCUSSION: Mean score was 64.29% ± 13.62. Comparatively, Group 1 obtained a higher score than Group 2 (70.63% ± 14.02 vs. 60.27% ± 11.94), although with no statistically significant difference (p = 0.063). The tasks most frequently accomplished were opioid administration (100%), rapid sequence technique (100%), pre-oxygenation (92%), gastric content aspiration prophylaxis (84%), and previous clinical history (84%). Conversely, the tasks less frequently accomplished were confirming presence of pediatrician (64%), oxytocin administration (56%), PONV prophylaxis (56%), and preoperative airway assessment (48%). CONCLUSION: The performance of the residents observed in this study was comparable to results previously published. The final score did not depend on the residency year.

Spinal cord infarction in children: Can gymnastics be a cause?

INTRODUCTION: Spinal cord infarction (SCI) in children is rare and difficult to diagnose. Fibrocartilaginous embolism (FCE) is probably the underlying cause for some unexplained cases of spinal cord infarcts. Abrupt back pain followed by a progressive syndrome of myelopathy appears to be the typical presentation, with a close temporal relationship between the onset of symptoms and preceding minor trauma. Supportive care and rehabilitation are essential in the treatment of children with SCI. CASE REPORT: A previously healthy 12-year-old girl who practiced acrobatic gymnastics was admitted to a rehabilitation centre 14 days after being diagnosed with an acute anterior SCI with no identified cause. Sensory modality of pin prick and light touch were impaired, with the former more significantly affected. She was not able to run and had difficulty on monopodal standing and performing motor sequencing. Additionally, she mentioned ineffective cough along with flatus incontinence and normal bladder function. After a 4-week multidisciplinary rehabilitation program her neurologic deficits improved. DISCUSSION: Given the patient's age and clinical presentation, a literature review led to the consideration of FCE as the most likely definitive diagnosis. It should be recognized as a cause of SCI especially in those involved in sport activities, even if previous trauma is denied.

Impact of urinary selective antibiogram in primary care / Impacto do antibiograma seletivo nas uroculturas em cuidados primários

ABSTRACT INTRODUCTION: Selective reporting of antibiotic susceptibility test results (selective antibiogram), is increasingly recognized as one of the key strategies of antibiotic stewardship programs. The objective of this study is to determine the impact of selective susceptibility reporting on ciprofloxacin utilization and Escherichia coli susceptibility to ciprofloxacin in the outpatient setting. MATERIAL AND METHODS: A selective reporting policy was created and implemented in 2011. The policy involves the non-reporting of ciprofloxacin susceptibility to Enterobacteriaceae isolated in a urine sample when there was susceptibility to other agents with narrow spectrum. The outcomes evaluated were outpatient ciprofloxacin utilization and E. coli susceptibility to ciprofloxacin between January 2011 and December 2018 RESULTS: Between 2011 and 2018 we detected an increased susceptibility rate of E. coli to ciprofloxacin from 79% to 87% (p < 0.001) and a decreased incidence rate of E. coli resistant to ciprofloxacin from 2.52 to 0.87 (p < 0.001). The ciprofloxacin dropped from 0.75 defined daily doses (DHD) to 0.36 DHD and there was a compensatory increase in nitrofurantoin and fosfomycin utilization. DISCUSSION: Our study showed that selective reporting can influence prescribing practice in a community level and encourages clinicians to select more narrow-spectrum and cost-effective antimicrobial agents in UTIs. CONCLUSION: Our results suggest that selective antibiogram should be considered an effective prevention strategy to reduce targeted antimicrobial utilization.

RESUMEN INTRODUCCIÓN: La notificación selectiva de resultados de la prueba de susceptibilidad bacteriana (antibiograma selectivo) es conocida como una de las estrategias clave de los programas de optimización de antimicrobianos. El objetivo de este estudio fue determinar el impacto del antibiograma selectivo en el consumo de ciprofloxacino y la sensibilidad de la bacteria Escherichia coli al ciprofloxacino en la atención básica. MATERIAL Y MÉTODOS: La política de informe selectivo fue creada e implementada en 2011 e incluyó la no trasmisión, en el antibiograma, de sensibilidad de Enterobacteriaceae al ciprofloxacino en muestras urinarias cuando había sensibilidad a otros agentes de espectro reducido. Los desenlaces evaluados fueron el consumo de ciprofloxacino y la evolución de sensibilidad de E. coli al ciprofloxacino entre enero de 2011 y diciembre de 2018. RESULTADOS En esse período, se detectó un aumento en la tasa de sensibilidad de E. coli al ciprofloxacino, del 79% al 87% (p < 0,001). La tasa de incidencia de E. coli resistente al ciprofloxacino descendió de 2,52 a 0,87 (p < 0,001). El consumo de ciprofloxacino tuvo un descenso de 0,75 doses por mil habitantes día (DHD) a 0,36 DHD. Al mismo tiempo, un aumento compensatorio se observó en el consumo de nitrofurantoína y fosfomicina. DISCUSIÓN: Nuestro estudio demostró que el uso del antibiograma selectivo influyó en la práctica de prescripción de antimicrobianos y animó a los médicos generales a elegir antimicrobianos de espectro más reducido y con mejor relación de costo-beneficio. CONCLUSIÓN: Nuestros resultados sugieren que la utilización de antibiogramas selectivos debe ser considerada una estrategia efectiva en la reducción del consumo de determinados antimicrobianos.

RESUMO INTRODUÇÃO: A notificação seletiva dos resultados do teste de suscetibilidade aos antimicrobianos (antibiograma seletivo) é conhecida como uma das estratégias-chave dos programas de apoio à prescrição de antibióticos. O objetivo deste estudo foi determinar o impacto do antibiograma seletivo no consumo de ciprofloxacino e a suscetibilidade da bactéria Escherichia coli ao ciprofloxacino nos cuidados primários. MATERIAL E MÉTODOS: A política de notificação seletiva foi criada e implementada em 2011 e envolveu a não transmissão, no antibiograma, da suscetibilidade da família Enterobacteriaceae ao ciprofloxacino em amostras urinárias quando existia suscetibilidade a outros agentes com menor espectro. Os desfechos avaliados foram consumo de ciprofloxacino e evolução da suscetibilidade de E. coli ao ciprofloxacino entre janeiro de 2011 e dezembro de 2018. RESULTADOS: Nesse período, um aumento foi detectado na taxa de suscetibilidade de E. coli ao ciprofloxacino, de 79% a 87% (p < 0,001). A taxa de incidência de E. coli resistente ao ciprofloxacino diminuiu de 2,52 para 0,87 (p < 0,001). O consumo de ciprofloxacino teve uma queda de 0,75 doses diárias definidas (DHD) para 0,36 DHD. Simultaneamente, um aumento compensatório foi observado no consumo de nitrofurantoína e fosfomicina. DISCUSSÃO: Nosso estudo demonstrou que a utilização do antibiograma seletivo influenciou a prática de prescrição dos antimicrobianos e incentivou os clínicos gerais a selecionar antimicrobianos de espectro de ação mais reduzido e com melhor relação custo-benefício. CONCLUSÃO: Nossos resultados sugerem que a utilização de antibiogramas seletivos deve ser considerada uma estratégia eficaz na redução do consumo de determinados antimicrobianos.

Application of AR and VR in hand rehabilitation: A systematic review.

BACKGROUND: The human hand is the part of the body most frequently injured in work related accidents, accounting for a third of all accidents at work and often involving surgery and long periods of rehabilitation. Several applications of Augmented Reality (AR) and Virtual Reality (VR) have been used to improve the rehabilitation process. However, there is no sound evidence about the effectiveness of such applications nor the main drivers of therapeutic success. OBJECTIVES: The objective of this study was to review the efficacy of AR and VR interventions for hand rehabilitation. METHODS: A systematic search of publications was conducted in October 2019 in IEEE Xplore, Web of Science, Cochrane library, and PubMed databases. Search terms were: (1) video game or videogame, (2) hand, (3) rehabilitation or therapy and (4) VR or AR. Articles were included if (1) were written in English, (2) were about VR or AR applications, (3) were for hand rehabilitation, (4) the intervention had tests on at least ten patients with injuries or diseases which affected hand function and (5) the intervention had baseline or intergroup comparisons (AR or VR intervention group versus conventional physical therapy group). PRISMA protocol guidelines were followed to filter and assess the articles. RESULTS: From the eight selected works, six showed improvements in the intervention group, and two no statistical differences between groups. We were able to identify motivators of patients' adherence, namely real-time feedback to the patients, challenge, and increased individualized difficulty. Automated tracking, easy integration in the home setting and the recording of accurate metrics may increase the scalability and facilitate healthcare professionals' assessments. CONCLUSIONS: This systematic review provided advantages and drivers for the success of AR/VR application for hand rehabilitation. The available evidence suggests that patients can benefit from the use of AR or VR interventions for hand rehabilitation.

Quantum key distribution with correlated sources.

In theory, quantum key distribution (QKD) offers information-theoretic security. In practice, however, it does not due to the discrepancies between the assumptions used in the security proofs and the behavior of the real apparatuses. Recent years have witnessed a tremendous effort to fill the gap, but the treatment of correlations among pulses has remained a major elusive problem. Here, we close this gap by introducing a simple yet general method to prove the security of QKD with arbitrarily long-range pulse correlations. Our method is compatible with those security proofs that accommodate all the other typical device imperfections, thus paving the way toward achieving implementation security in QKD with arbitrary flawed devices. Moreover, we introduce a new framework for security proofs, which we call the reference technique. This framework includes existing security proofs as special cases, and it can be widely applied to a number of QKD protocols.

Critical Results Reporting in Portuguese Hospital Laboratories: State-of-the-Art.

INTRODUCTION: This survey aimed to assess the state-of-the-art of current practices on critical results reporting among Portuguese Clinical Pathology Laboratories. The results of the survey will set basis for future standardization and national guideline development. MATERIALS AND METHODS: The survey was transmitted to 49 Clinical Pathology Laboratories among public hospitals inserted in the Portuguese National Health System. In 27 questions, laboratories were asked about their critical results procedures, critical results list, reporting and further education. Data were analyzed using Microsoft Excel v.2016 and MedCalc Statistical Software version 12.5.0.0 (Ostend, Belgium). Where applicable, the comparison of proportions was used to estimate the level of significance (P<0.05). RESULTS: The response rate was 44/49 (90%), including 36 participants with a defined critical results reporting procedure. Among them, 31 laboratories defined a critical results list, mainly based on published literature (27/31). There was a statistically significant number of laboratories (P=0.019, 24/30) that report different critical results depending on the patient's age, but regardless of disease, ethnicity and location (P>0.05). The majority of laboratories (60%) report critical results via telephone within 15 minutes. Critical results are usually reported by clinical pathologists to physicians. Twenty-five laboratories periodically reevaluate their critical results list. CONCLUSION: Despite the fact that most of the Portuguese hospitals have a critical results policy, this survey showed high variability among the hospitals concerning critical results reporting practices and critical results list. This survey points out that nationally established procedures and guidelines are urgent step for critical results standardization.

The environment contribution to gender differences in childhood obesity and organized sports engagement.

OBJECTIVE: This study aims to analyze gender-specific associations between sports activity outside of school and obesity, observing to what extent the local built environment contributes to the patterns found. METHODS: A total of 2253 children aged 6.0-11.0 years were assessed: 49.3% girls and 50.7% boys. Children's weight and height were measured, age and sex-specific BMI cut-off points were used to define normal vs overweight/obesity. Children's organized sports (OS) activity was assessed by questionnaire, and local facilities for children's engagement in OS were analyzed. Logistic regression models were computed, adjusted for confounding variables. RESULTS: Results showed greater overweight and obesity (25.1% vs 20.1%) and lower OS engagement (66.5% vs 73.8%) in girls as well as greater impact of OS engagement on weight status in girls (OR for having a normal weight = 1.434 in girls vs 1.043 in boys). Additionally, opportunities to engage in OS were scarce for girls. CONCLUSIONS: The gender gap in children's weight status and OS engagement might be enhanced by an environmental mismatch that undermines girls' opportunities to play sports. There should be more opportunities for girls to engage in their favorite sports as a means to tackle the obesity epidemic and to promote gender equality.

Synthesis and Biological Evaluation of Structurally Varied 5'-/6'-Isonucleosides and Theobromine-Containing N-Isonucleosidyl Derivatives.

Isonucleosides are rather stable regioisomeric analogs of nucleosides with broad therapeutic potential. We have previously demonstrated the ability of 5' and 6'-isonucleosides to inhibit the activity of acetylcholinesterase, a major target for Alzheimer's disease therapy. Continuing with our research on this topic, we report herein on the synthesis and biological evaluation of a variety of novel terminal isonucleosides and theobromine isonucleotide analogs. Xylofuranose-based purine or uracil 5'-isonucleosides and xylofuranos-5'-yl or glucos-6'-yl theobromine derivatives were accessed via Mitsunobu coupling between partially protected xylofuranose or glucofuranose derivatives with a nucleobase using conventional or microwave-assisted heating conditions. Theobromine-containing N-isonucleosidyl sulfonamide and phosphoramidate derivatives were synthesized from isonucleosidyl acetate precursors. The most active compounds in the cholinesterase inhibition assays were a glucopyranose-based theobromine isonucleosidyl acetate, acting as a dual inhibitor of acetylcholinesterase (AChE, Ki = 3.1 µM) and butyrylcholinesterase (BChE, Ki = 5.4 µM), and a 2-O,4-O-bis-xylofuranos-5'-yl uracil derivative, which displayed moderate inhibition of AChE (Ki = 17.5 µM). Docking studies revealed that the active molecules are positioned at the gorge entrance and at the active site of AChE. None of the compounds revealed cytoxic activity to cancer cells as well as to non-malignant mouse fibroblasts.

Describing studies on childhood obesity determinants by Socio-Ecological Model level: a scoping review to identify gaps and provide guidance for future research.

Childhood obesity is increasing worldwide and is a major public health concern once children with obesity are at higher risk for several diseases and are often stigmatized. Children with obesity are more likely to become adults with obesity with greater needs of healthcare. Determinants of childhood obesity might be grouped in five levels according to the Socio-Ecological Model (SEM): individual, interpersonal, institutional, community and policies. This scoping review emerged from the need to identify which determinants of childhood obesity have been more frequently studied (and how) and which require more investigation. The main objectives were to quantify studies on the determinants of childhood obesity by SEM level addressed, to identify gaps in the literature regarding the studied SEM level(s), to describe the studies' characteristics and to provide guidance for SEM levels that need further investigation. This scoping review follows the five-stage protocol methodology proposed by Arksey and O'Malley in 2005. PubMed database was systematically searched, and hand-searches also took place. The search yielded 975 results from which 552 were excluded after title and abstract reading. The remaining 423 results were fully read and information about methodologic aspects, namely study design, sample size, sample constitution (children, dyads or/and parents) and children's age as well as the SEM level determinants addressed was retrieved. Despite the consensus about the appropriateness of SEM as a framework to comprehensively examine childhood obesity determinants, studies addressing all SEM levels determinants jointly or the policies level determinants alone were not found. Other gaps shown were: the small number of studies that included the policies level determinants alongside determinants from other levels (N = 10) and studies using cohorts study design (ranging from 2 to 28 per SEM level). These gaps should be considered when planning future research.

Multiscale information storage of linear long-range correlated stochastic processes.

Information storage, reflecting the capability of a dynamical system to keep predictable information during its evolution over time, is a key element of intrinsic distributed computation, useful for the description of the dynamical complexity of several physical and biological processes. Here we introduce a parametric approach which allows one to compute information storage across multiple timescales in stochastic processes displaying both short-term dynamics and long-range correlations (LRC). Our analysis is performed in the popular framework of multiscale entropy, whereby a time series is first "coarse grained" at the chosen timescale through low-pass filtering and downsampling, and then its complexity is evaluated in terms of conditional entropy. Within this framework, our approach makes use of linear fractionally integrated autoregressive (ARFI) models to derive analytical expressions for the information storage computed at multiple timescales. Specifically, we exploit state space models to provide the representation of lowpass filtered and downsampled ARFI processes, from which information storage is computed at any given timescale relating the process variance to the prediction error variance. This enhances the practical usability of multiscale information storage, as it enables a computationally reliable quantification of a complexity measure which incorporates the effects of LRC together with that of short-term dynamics. The proposed measure is first assessed in simulated ARFI processes reproducing different types of autoregressive dynamics and different degrees of LRC, studying both the theoretical values and the finite sample performance. We find that LRC alter substantially the complexity of ARFI processes even at short timescales, and that reliable estimation of complexity can be achieved at longer timescales only when LRC are properly modeled. Then, we assess multiscale information storage in physiological time series measured in humans during resting state and postural stress, revealing unprecedented responses to stress of the complexity of heart period and systolic arterial pressure variability, which are related to the different role played by LRC in the two conditions.

The role of urban design in childhood obesity: A case study in Lisbon, Portugal.

OBJECTIVE: We hypothesize that physical features of the urban environment might enhance or prevent childhood obesity. Thus, this study's main goal was to verify if there is an association between the neighborhood urban design and childhood obesity-independent of well-known childhood obesity determinants, such as, father's level of schooling (as a proxy for socioeconomic status), and parent's weight status. METHODS: This study classifies neighborhoods according to land use and building features using hierarchical clusters analysis and examines their association with childhood obesity through logistic regression models. RESULTS: Four clusters resulted from the analysis: Cluster 1 represents areas with older buildings and mixed land use, cluster 2 is an area with small rented buildings and urban areas, cluster 3 comprises newer buildings with parking and urban green space, and cluster 4 is a forest area. Living in cluster 3 protects from childhood obesity, even when adjusting for father's level of schooling or parent's weight status. CONCLUSIONS: There are distinct urban configurations in Lisbon's municipality and children who live in Cluster 3 (more recent and greener neighborhoods) seem to be protected from obesity. Therefore, public policy should focus on healthy urban planning at the neighborhood level, to promote positive impacts on peoples' health.