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Healthcare costs for low back pain (LBP) are increasing rapidly. Hence, it is important to provide treatments that are effective and cost-effective. The purpose of this systematic review was to investigate the cost-effectiveness of guideline-endorsed treatments for LBP. We searched nine clinical and economic electronic databases and the reference list of relevant systematic reviews and included studies for eligible studies. Economic evaluations conducted alongside randomised controlled trials investigating treatments for LBP endorsed by the guideline of the American College of Physicians and the American Pain Society were included. Two independent reviewers screened search results and extracted data. Data extracted included the type and perspective of the economic evaluation, the treatment comparators, and the relative cost-effectiveness of the treatment comparators. Twenty-six studies were included. Most studies found that interdisciplinary rehabilitation, exercise, acupuncture, spinal manipulation or cognitive-behavioural therapy were cost-effective in people with sub-acute or chronic LBP. Massage alone was unlikely to be cost-effective. There were inconsistent results on the cost-effectiveness of advice, insufficient evidence on spinal manipulation for people with acute LBP, and no evidence on the cost-effectiveness of medications, yoga or relaxation. This review found evidence supporting the cost-effectiveness of the guideline-endorsed treatments of interdisciplinary rehabilitation, exercise, acupuncture, spinal manipulation and cognitive-behavioural therapy for sub-acute or chronic LBP. There is little or inconsistent evidence for other treatments endorsed in the guideline. [ABSTRACT FROM AUTHOR]

Care from a general practitioner (GP) is one of the most frequently utilised healthcare services for people with low back pain and only a small proportion of those with low back pain who seek care from a GP are referred to other services. The aim of this systematic review was to evaluate the evidence on cost-effectiveness of GP care in non-specific low back pain. We searched clinical and economic electronic databases, and the reference list of relevant systematic reviews and included studies to June 2010. Economic evaluations conducted alongside randomised controlled trials with at least one GP care arm were eligible for inclusion. Two reviewers independently screened search results and extracted data. Eleven studies were included; the majority of which conducted a cost-effectiveness or cost-utility analysis. Most studies investigated the cost-effectiveness of usual GP care. Adding advice, education and exercise, or exercise and behavioural counselling, to usual GP care was more cost-effective than usual GP care alone. Clinical rehabilitation and/or occupational intervention, and acupuncture were more cost-effective than usual GP care. One study investigated the cost-effectiveness of guideline-based GP care, and found that adding exercise and/or spinal manipulation was more cost-effective than guideline-based GP care alone. In conclusion, GP care alone did not appear to be the most cost-effective treatment option for low back pain. GPs can improve the cost-effectiveness of their treatment by referring their patients for additional services, such as advice and exercise, or by providing the services themselves. [ABSTRACT FROM AUTHOR]

Several versions of the 24-item Roland Morris Disability Questionnaire (RMDQ) have been proposed; however, their responsiveness has not been extensively explored. The objective of this study was to compare the responsiveness of four versions of the RMDQ. Perceived disability was measured using the 24-item, two 18-item and an 11-item RMDQ on 1,069 low back pain patients from six randomised controlled trials. Responsiveness was calculated using effect size, Guyatt's responsiveness index (GRI) and receiver operating characteristics (ROC) curves. Effect size analyses showed that both 18-item versions of the RMDQ were superior to the 24- and 11-item versions of the RMDQ. GRI showed that the 24- and 18-item versions of the RMDQ were similar but more responsive than the 11-item. ROC curves revealed that the 11-item was less responsive than the other three versions, which had similar responsiveness. The results of this study demonstrate that the 24-item and both 18-item versions of the RMDQ have similar responsiveness with all having superior responsiveness to the 11-item. [ABSTRACT FROM AUTHOR]

Protein dynamics is essential for various biological processes, influencing functions such as enzyme activity, molecular recognition, and signal transduction. However, traditional protein engineering methods often focus on static structures, lacking tools to precisely manipulate dynamic behaviors. Here, we developed Mutational Energy Landscape Trap (MELT), a novel method designed to control protein dynamics by combining Normal Mode Analysis (NMA) and in silico mutagenesis. MELT works by displacing protein structures along low-frequency normal modes and introducing mutations to either lock proteins in these conformations or increase dynamics along the chosen normal modes. We tested MELT using hen-egg lysozyme as a model system. The method was validated by monitoring relevant collective coordinates during molecular dynamics simulations and evaluation of the collective movements of each construct. Our experiments showed that MELT was able to consistently create new protein sequences with the desired dynamical behavior in simulations. It demonstrates its potential for applications in the field of protein engineering, being an unprecedented way of manipulating protein features.

We report a rapid, efficient, and scope-extensive approach for the late-stage electrochemical diselenation of BODIPYs. Photophysical analyses reveal red-shifted absorption - corroborated by TD-DFT and DLPNO-STEOM-CCSD computations - and color-tunable emission with large Stokes shifts in the selenium-containing derivatives compared to their precursors. In addition, due to the presence of the heavy Se atoms, competitive ISC generates triplet states which sensitize 1 O 2 and display phosphorescence in PMMA films at RT and in a frozen glass matrix at 77 K. Importantly, the selenium-containing BODIPYs demonstrate the ability to selectively stain lipid droplets, exhibiting distinct fluorescence in both green and red channels. This work highlights the potential of electrochemistry as an efficient method for synthesizing unique emission-tunable fluorophores with broad-ranging applications in bioimaging and related fields., (© 2023 Wiley-VCH GmbH.)

In this work, the synthesis, characterization and photophysical assays of a new trans -A 2 B-corrole derivative from the naturally occurring quinone are described. β-Lapachone is a naturally occurring quinoidal compound that provides highly fluorescent heterocyclic compounds such as lapimidazoles. The new trans -A 2 B-corrole compound was obtained from the reaction between 2,3,4,5,6-(pentafluorophenyl)dipyrromethane and the lapimidazole bearing an aldehyde group. The dyad was characterized by high-resolution mass spectrometry (HRMS), NMR spectroscopy ( 1 H, COSY 2D, HMBC, 19 F), FT-IR, UV-vis, steady-state and time-resolved fluorescence, electrochemical studies (CV), TD-DFT analysis and photobiological experiments, in which includes aggregation, stability in solution, photostability and partition coefficients assays. Finally, ROS generation assays were performed using 1,3-diphenylisobenzofuran (DPBF) method and the presented compound showed significant photostability and singlet oxygen production., Competing Interests: The authors declare that they do not have conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: There is widespread agreement amongst clinicians that people with non-specific low back pain (NSLBP) comprise a heterogeneous group and that their management should be individually tailored. One treatment known by its tailored design is the McKenzie method (e.g. an individualized program of exercises based on clinical clues observed during assessment)., Objectives: To evaluate the effectiveness of the McKenzie method in people with (sub)acute non-specific low back pain., Search Methods: We searched CENTRAL, MEDLINE, Embase and two trials registers up to 15 August 2022., Selection Criteria: We included randomized controlled trials (RCTs) investigating the effectiveness of the McKenzie method in adults with (sub)acute (less than 12 weeks) NSLBP., Data Collection and Analysis: We used standard methodological procedures expected by Cochrane., Main Results: This review included five RCTs with a total of 563 participants recruited from primary or tertiary care. Three trials were conducted in the USA, one in Australia, and one in Scotland. Three trials received financial support from non-commercial funders and two did not provide information on funding sources. All trials were at high risk of performance and detection bias. None of the included trials measured adverse events. McKenzie method versus minimal intervention (educational booklet; McKenzie method as a supplement to other intervention - main comparison) There is low-certainty evidence that the McKenzie method may result in a slight reduction in pain in the short term (MD -7.3, 95% CI -12.0 to -2.56; 2 trials, 377 participants) but not in the intermediate term (MD -5.0, 95% CI -14.3 to 4.3; 1 trial, 180 participants). There is low-certainty evidence that the McKenzie method may not reduce disability in the short term (MD -2.5, 95% CI -7.5 to 2.0; 2 trials, 328 participants) nor in the intermediate term (MD -0.9, 95% CI -7.3 to 5.6; 1 trial, 180 participants). McKenzie method versus manual therapy There is low-certainty evidence that the McKenzie method may not reduce pain in the short term (MD -8.7, 95% CI -27.4 to 10.0; 3 trials, 298 participants) and may result in a slight increase in pain in the intermediate term (MD 7.0, 95% CI 0.7 to 13.3; 1 trial, 235 participants). There is low-certainty evidence that the McKenzie method may not reduce disability in the short term (MD -5.0, 95% CI -15.0 to 5.0; 3 trials, 298 participants) nor in the intermediate term (MD 4.3, 95% CI -0.7 to 9.3; 1 trial, 235 participants). McKenzie method versus other interventions (massage and advice) There is very low-certainty evidence that the McKenzie method may not reduce disability in the short term (MD 4.0, 95% CI -15.4 to 23.4; 1 trial, 30 participants) nor in the intermediate term (MD 10.0, 95% CI -8.9 to 28.9; 1 trial, 30 participants)., Authors' Conclusions: Based on low- to very low-certainty evidence, the treatment effects for pain and disability found in our review were not clinically important. Thus, we can conclude that the McKenzie method is not an effective treatment for (sub)acute NSLBP., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Litter pollution is a global environmental problem that occurs in virtually all ecosystems. Scientific research on anthropogenic litter and its environmental impacts focusses predominantly on plastics and the marine environment. Little empirical knowledge exists about the distribution and ecological impacts of litter in terrestrial environments, where most litter is produced. To start closing that knowledge gap, we investigated the distribution of litter in a cultural landscape in central Norway and in relation to land cover types. We registered and collected litter in 110 survey plots that were randomly stratified across various land cover types. Our results show that land cover type modulates the occurrence, abundance, fragments size, and that litter is most present and abundant in or near land cover types associated with high human activities. Plastic was by far the most common litter material type, although the litter community (in terms of materials type) was not independent from land cover type. This knowledge can help to inform and optimize litter management and clean-up activities in terrestrial landscapes. How and to what extent the spatial structure of the litter community mediates ecological effects across various land cover types remains unknown to a large extent and warrants further study., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Eide et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Short-term fasting is beneficial for the regeneration of multiple tissue types. However, the effects of fasting on muscle regeneration are largely unknown. Here, we report that fasting slows muscle repair both immediately after the conclusion of fasting as well as after multiple days of refeeding. We show that ketosis, either endogenously produced during fasting or a ketogenic diet or exogenously administered, promotes a deep quiescent state in muscle stem cells (MuSCs). Although deep quiescent MuSCs are less poised to activate, slowing muscle regeneration, they have markedly improved survival when facing sources of cellular stress. Furthermore, we show that ketone bodies, specifically β-hydroxybutyrate, directly promote MuSC deep quiescence via a nonmetabolic mechanism. We show that β-hydroxybutyrate functions as an HDAC inhibitor within MuSCs, leading to acetylation and activation of an HDAC1 target protein p53. Finally, we demonstrate that p53 activation contributes to the deep quiescence and enhanced resilience observed during fasting., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)

Metal catalyzed C-H functionalization offers a versatile platform for methodology development and a wide variety of reactions now exist for the chemo- and site-selective functionalization of organic molecules. Cyclopentadienyl-metal (CpM) complexes of transition metals and their correlative analogues have found widespread application in this area, and herein we highlight several key applications of commonly used transition-metal Cp-type catalysts. In addition, an understanding of transition metal Cp-type catalyst synthesis is important, particularly where modifications to the catalyst structure are required for different applications, and a summary of this aspect is given.

Background/objective: Chronic knee pain (CKP) is a common pain complaint in older adults that is often associated with disability. This study investigated the relationship between 2 components of subjective well-being (depressive symptoms and life satisfaction) and CKP phenotypes based on the presence of knee disability., Methods: A cross-sectional study was performed at baseline of ELSA-Brasil Musculoskeletal cohort (2012-2014). Chronic knee pain phenotypes were identified according to the presence of CKP that was accompanied or not by disability, which was assessed by a question on pain-related limitations to perform everyday activities (overall), Western Ontario and McMaster Universities Osteoarthritis Index's physical function subscale (daily tasks) and 5-times sit-to-stand test (objective). Depressive symptoms were assessed by the Clinical Interview Schedule-Revised and life satisfaction by the Satisfaction With Life Scale. Multinomial logistic regressions used CKP phenotypes as response variables (no CKP as reference)., Results: The sample comprised 2898 participants (mean age, 55.9 ± 8.9 years; 52.9% were female). After adjustments for sociodemographic and clinical factors, depressive symptoms were associated with daily tasks disabling CKP (odds ratio [OR], 2.30; 95% confidence interval [CI], 1.45-3.66) and objective disabling CKP (OR, 1.95; 95% CI, 1.29-2.93) and with nondisabling CKP for the overall disability measure (OR, 1.54; 95% CI, 1.17-2.04). Life satisfaction was inversely associated with all phenotypes in fully adjusted models, with strongest magnitude of associations observed for disabling CKP., Conclusions: The association of depressive symptoms and life satisfaction with CKP phenotypes suggest the need to address both negative and positive components of subjective well-being in the assessment of individuals with knee complaints., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Synthetic organic chemistry has witnessed a plethora of functionalization and defunctionalization strategies. In this regard, C-H functionalization has been at the forefront due to the multifarious applications in the development of simple to complex molecular architectures and holds a brilliant prospect in drug development and discovery. Despite been explored tremendously by chemists, this functionalization strategy still enjoys the employment of novel metal catalysts as well metal-free organic ligands. Moreover, the switch to photo- and electrochemistry has widened our understanding of the alternative pathways via which a reaction can proceed and these strategies have garnered prominence when applied to C-H activation. Synthetic chemists have been foraging for new directing groups and templates for the selective activation of C-H bonds from a myriad of carbon-hydrogen bonds in aromatic as well as aliphatic systems. As a matter of fact, by varying the templates and directing groups, scientists found the answer to the challenge of distal C-H bond activation which remained an obstacle for a very long time. These templates have been frequently harnessed for selectively activating C-H bonds of natural products, drugs, and macromolecules decorated with multiple C-H bonds. This itself was a challenge before the commencement of this field as functionalization of a site other than the targeted site could modify and hamper the biological activity of the pharmacophore. Total synthesis and pharmacophore development often faces the difficulty of superfluous reaction steps towards selective functionalization. This obstacle has been solved by late-stage functionalization simply by harnessing C-H bond activation. Moreover, green chemistry and metal-free reaction conditions have seen light in the past few decades due to the rising concern about environmental issues. Therefore, metal-free catalysts or the usage of non-toxic metals have been recently showcased in a number of elegant works. Also, research groups across the world are developing rational strategies for directing group free or non-directed protocols that are just guided by ligands. This review encapsulates the research works pertinent to C-H bond activation and discusses the science devoted to it at the fundamental level. This review gives the readers a broad understanding of how these strategies work, the execution of various metal catalysts, and directing groups. This not only helps a budding scientist towards the commencement of his/her research but also helps a matured mind searching out for selective functionalization. A detailed picture of this field and its progress with time has been portrayed in lucid scientific language with a motive to inculcate and educate scientific minds about this beautiful strategy with an overview of the most relevant and significant works of this era. The unique trait of this review is the detailed description and classification of various directing groups and their utility over a wide substrate scope. This allows an experimental chemist to understand the applicability of this domain and employ it over any targeted substrate., (© 2021 Wiley-VCH GmbH.)

Glucantime (Sb V ) is the first-line treatment against American Tegumentary Leishmaniasis. Resistance cases to this drug have been reported and related to host characteristics and parasite phenotypes. In this study, 12 Leishmania (Viannia) braziliensis isolates from patients that presented clinical cure (Responders-R) and relapse or therapeutic failure (Non-responders-NR) after treatment with antimony, were analyzed. These parasites were assessed by in vitro susceptibility to Sb III and Sb V , serine proteases activity measured with substrate (z-FR-AMC) and specific inhibitors (TLCK, AEBSF and PMSF). In vitro susceptibility of axenic amastigotes to Sb III showed a significant difference between R and NR groups. The protease assays showed that TLCK inhibited almost 100% of activity in both axenic amastigotes and promastigotes while AEBSF inhibited around 70%, and PMSF showed lower inhibition of some isolates. Principal component and clustering analysis performed with these data yielded one homogeneous cluster with only NR isolates and three heterogeneous clusters with R and NR isolates. Additionally, differential expression of subtilisins (LbrM.13.0860 and LbrM.28.2570) and TXNPx (LbrM.15.1080) was evaluated in promastigotes and axenic amastigotes from both groups. The results showed a higher expression of LbrM.13.0860 and LbrM.15.1080 genes in axenic amastigotes, while LbrM.28.2570 gene had the lowest expression in all isolates, regardless of the parasite form. The data presented here show a phenotypic heterogeneity among the parasites, suggesting that exploration of in vitro phenotypes based on Sb III and serine proteases profiles can aid in the characterization of L. (V.) braziliensis clinical isolates., (© 2021. The Author(s).)

Pyoderma gangrenosum manifests as an ulceration of the skin often associated with several systemic diseases. The diagnosis is usually made by exclusion criteria with suggestions made by clinical findings and histological features. It can occur any site but more common in the legs. Advances in translational medicine led to the development of new forms of therapy in chronic inflammatory diseases by the oral administration of Janus kinase inhibitors. We report two cases of chronic ulceration of the skin consistent with the diagnosis of Pyoderma Gangrenosum that went into complete remission after the use of baricitinib., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Tuberculosis still remains a concerning health problem worldwide. Its etiologic agent, Mycobacterium tuberculosis , continues to be the focus of research to unravel new prophylactic and therapeutic strategies against this disease. The only vaccine in use against tuberculosis is based on the in vitro attenuated strain, M. bovis BCG. Dodecin is a dodecameric complex important for flavin homeostasis in Archea and Eubacteria, and the M. tuberculosis protein is described as thermo- and halostable. M. bovis BCG Moreau, the Brazilian vaccine strain, has a single nucleotide polymorphism in the dodecin start codon, leading to a predicted loss of seven amino acids at the protein N-terminal end. In this work we aimed to characterize the effect of this mutation in the BCG Moreau protein features. Our recombinant protein assays show that the predicted BCG homolog is less thermostable than M.tb 's but maintains its dodecamerization ability, although with a lower riboflavin-binding capacity. These data are corroborated by structural analysis after comparative modeling, showing that the predicted BCG dodecin complex has a lower interaction energy among its monomers and also a distinct electrostatic surface near the flavin binding pocket. However, western blotting assays with the native proteins were unable to detect significant differences between the BCG Moreau and M.tb orthologs, indicating that other factors may be modulating protein structure/function in the bacterial context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Schwarz, Luzes, Correa, Silva-Gonçalves, Machado, Guimarães and Mendonça-Lima.)

Objectives: To evaluate the influence of self-reported physical activity and sleep quality on conditioned pain modulation (CPM) in the orofacial region., Materials and Methods: Ninety healthy participants aged 18-50 years old were evenly distributed according to the level of physical activity into low, moderate, and high level. The classification of physical activity was based on modified criteria of the International Physical Activity Questionnaire (IPAQ), considering intensity, duration, and frequency of physical activity. The Pittsburgh Sleep Quality Index (PSQI) assessed sleep quality and the individuals were then classified as good or poor sleepers. CPM was assessed using the pressure pain threshold (PPT) of the anterior temporalis as test stimulus and hand immersion in hot water as conditioning stimulus. ANOVA was applied to the data and Tukey's posttest was applied when the main effects or interactions were significant (p < 0.050)., Results: There was no significant main effect of neither physical activity nor sleep quality on pain modulation. However, individuals who reported high level of physical activity and good quality of sleep had a greater pain modulation (- 0.60 ± 0.34) when compared with those who reported moderate (- 0.10 ± 0.25) and low level of physical activity (- 0.10 ± 0.52) and good sleep quality (p < 0.028)., Conclusions: Pain modulation seems to be more efficient in individuals who report a good sleep quality and a high level of physical activity., Clinical Relevance: Conditioned pain modulation is highly variable in healthy people. Therefore, a multifactorial approach should be taken into consideration in the evaluation of the efficacy of endogenous analgesia.

Over the past few decades, regioselective catalytic C-H functionalization has provided an attractive tool for unique retrosynthetic disconnections. The advancement of the directing group strategy in metal catalyzed synthetic transformation has contributed significantly to the incorporation of a wide range of functionalization reactions in both aromatic systems and aliphatic backbones. However, the extensive utilization of these methodologies depends on the ease of removal of the directing group to restore the free functional group. In this review, we have summarised the reported approaches for removing/modifying versatile directing groups.

There is increasing evidence that neurofilament light chain (NF-L) can be considered as a biomarker for neuro-axonal damage. This polypeptide can be released into the cerebrospinal fluid (CSF) and the blood, where it can be quantified. The concentration of NF-L is elevated in patients with multiple sclerosis (MS) and psychiatric disorders. We aimed to investigate the NF-L levels in the CSF from treated MS patients and the relationship with depression or anxiety. The study involved three groups: control group (individuals without inflammation), the relapse-remitting multiple sclerosis (RRMS)-untreated group, and the RRMS-Fingo group (RRMS patients who were treated with fingolimod). MS disability was assessed by the Expanded Disability Status Scale, and depression and anxiety were evaluated by a neuropsychologist, using the Hospital Anxiety and Depression Scale, the Beck Depression Inventory-II, and the Beck Anxiety Inventory. Individual CSF samples were collected to measure NF-L levels. The results of the statistical analysis on levels of NF-L in the CSF of control subjects, RRMS-untreated patients, and RRMS-Fingo patients were significant. The relationship between depression and anxiety in RRMS-Fingo patients and NF-L levels was not statistically significant. In conclusion, MS events such as anxiety and depression appear to contribute to the onset of clinical relapses, subclinical cases, and neurodegeneration.

Aims: To evaluate the influence of self-reported physical activity level on painful mechanical somatosensory profile and psychosocial characteristics., Methods: A total of 90 participants, male and female, were divided into three groups based on the frequency, duration, and intensity of physical activity over the last 3 months. The classification followed a modified criterion of the short version of the International Physical Activity Questionnaire (IPAQ). Mechanical quantitative sensory tests were performed in the region of the anterior temporalis muscle and on the thenar area of the dominant hand, and psychosocial aspects were assessed using questionnaires measuring state and trait anxiety, pain catastrophizing, lifestyle, and quality of life., Results: There was no significant main effect of group on any of the somatosensory variables (F < 0.34 and P > .416). As for psychosocial aspects, the low level of physical activity group had the lowest scores on the lifestyle questionnaire (P < .009)., Conclusion: Level of physical activity did not significantly influence mechanical somatosensory thresholds or temporal summation in the orofacial region, and worse quality of life was found in participants reporting a low level of physical activity.

HIV-1 integrase is the enzyme responsible for integrating the viral DNA into the host genome and is one of the main targets for antiretroviral therapy; however, there are documented cases of resistance against all the currently used integrase strand transfer inhibitors (INSTIs). While some resistance-related mutations occur near the inhibitor's binding site, the mutation N155H occurs on the opposite side of the drug-interacting Mg 2+ ions, thus, not interacting directly with the drug molecules and currently lacking an explanation for its resistance mechanism. Moreover, mutation N155H and the resistance-related mutation Q148H are mutually exclusive for unknown reasons. In the present study, we use molecular dynamics simulations to understand the impact of the N155H mutation in the HIV-1 integrase structure and dynamics, when alone or in combination with Q148H. Our findings suggest that the Mg 2+ ions of the active site adopt different orientations in each of the mutants, causing the catalytic triad residues involved in the ion coordination to adapt their side-chain configurations, completely changing the INSTIs binding site. The change in the ion coordination also seems to affect the flexibility of the terminal viral DNA nucleotide near the active site, potentially impairing the induced-fit mechanism of the drugs. The explanations obtained from our simulations corroborate previous hypotheses drawn from crystallographic studies. The proposed resistance mechanism can also explain the resistance caused by other mutations that take place in the same region of the integrase and help uncover the structural details of other HIV-1 resistance mechanisms., (Copyright © 2020 Machado and Guimarães.)

Background and Purpose- Sleep apnea has been associated with a poor outcome in acute stroke patients. Polysomnography is the gold standard diagnostic method for sleep apnea, but it is not feasible as a routine in the acute stroke setting. The current generation of positive airway pressure (PAP) devices can detect the different types of respiratory events. This study aimed to compare the algorithms used in PAP device to manually scored events on polysomnography in patients with acute stroke. Methods- A sleep study was performed with standard polysomnography and PAP device, simultaneously, within the first 48 hours after acute stroke onset. Results- We prospectively evaluated 29 patients with acute stroke (59.5±12.1 years). The area under the receiver operating characteristic curve for each apnea-hypopnea index value was above 0.90 by PAP device. There was a good correlation of apnea-hypopnea index ( r s =0.92; P <0.001), hypopnea index ( r s =0.89; P <0.001), and apnea index ( r s =0.70; P <0.001) between device-detected events and manually scored polysomnography. Conclusions- Given the high frequency of sleep apnea during the acute phase of stroke and the complexity of a full polysomnography study in this setting, PAP device on diagnostic mode can be used as an alternative tool for sleep apnea detection in acute stroke patients.

Background: Chronic pain is known to increase health care use in high-income countries, but in Brazil, little is known., Objective: To investigate the association between chronic pain and health care use among Brazilian older adults and explore the relationship between pain severity and health care use., Methods: This cross-sectional study was derived from the population-based study Frailty in Brazilian Older People-FIBRA. Chronic pain, pain intensity and pain-related disability were assessed through additional telephone interviews. Health care use was measured by the number of doctor visits, hospitalization events and high health care use (highest quartile of the distribution for number of doctor visits) in the last 12 months. Associations were tested in regression analyses adjusted for predisposing, enabling and illness-level components from the Andersen Model., Results: The 383 participants were predominantly female (71.0%), mean age was 75.6 (6.1 SD). The prevalence of chronic pain was 30.0%. Chronic pain was associated with number of doctor visits [unstandardized B coefficient 1.48; 95% confidence interval (CI) = 0.35-2.62] and high health care use [odds ratios (OR) = 2.27; 95% CI = 1.39-3.72]. Pain intensity was associated with high health care use in univariate (OR = 1.13; 95% CI = 1.06-1.20) but not multivariate analysis (OR = 1.12; 95% CI = 0.94-1.33). Pain-related disability was not associated with any outcome., Conclusion: Chronic pain increased health care use among Brazilian older adults. Improving the quality of primary care management of individuals at greater risk of chronic pain should be a cornerstone of health policies directed towards reducing the personal and societal burden of ageing., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The human immunodeficiency virus type 1 (HIV-1) has several proteins of therapeutic importance, many of which are currently used as drug targets in antiretroviral therapy. Among these proteins is the integrase, which is responsible for the integration of the viral DNA into the host genome - a crucial step for HIV-1 replication. Given the importance of this protein in the replication process, three integrase inhibitors are currently used as an option for antiretroviral therapy: Raltegravir, Elvitegravir, and Dolutegravir. However, the crescent emergence of mutations that cause resistance to these drugs has become a worldwide health problem. In this study, we compared the variability of each position of the HIV-1 integrase sequence in clinical isolates of Raltegravir-treated and drug-naïve patients by calculating their Shannon entropies. A co-occurrence network was created to explore how mutations co-occur in patients treated with Raltegravir. Then, by building tridimensional models of the HIV-1 integrase intasomes, we investigated the relationship between variability, architecture, and co-occurrence. We observed that positions bearing some of the major resistance pathways are highly conserved among non-treated patients and variable among the treated ones. The residues involved in the three main resistance-related mutations could be identified in the same group when the positions were clustered according to their entropies. Analysis of the integrase architecture showed that the high-entropy residues S119, T124, and T125, are in contact with the host DNA, and their variations may have impacts in the protein-DNA recognition. The co-occurrence network revealed that the major resistance pathways N155H and Q148HR share more mutations with each other than with the Y143R pathway, this observation corroborates the fact that the N155H pathway is most commonly converted into Q148HRK than into Y143RCH pathway in patients' isolates. The network and the structure analysis also support the hypothesis that the resistance-related E138K mutation may be a mechanism to compensate for mutations in neighbor lysine residues to maintain DNA binding. The present study reveals patterns by which the HIV-1 integrase adapts during Raltegravir therapy. This information can be useful to comprehend the impacts of the drug in the enzyme, as well as help planning new therapeutic approaches.

Objective: To compare the performance of different knee osteoarthritis (OA) classification criteria in a subsample of subjects of ELSA-Brasil Musculoskeletal cohort (ELSA-Brasil MSK) in comparison with the clinical-radiographic evaluation of an experienced rheumatologist., Method: A cross-sectional study of the diagnostic accuracy of different knee OA classification criteria: radiographic OA, symptomatic OA, clinical and clinical-radiographic criteria of the American College of Rheumatology (ACR), and the definition proposed by the National Institute for Health and Care Excellence (NICE), UK. The study also evaluated some alternative definitions of OA including a combination of criteria. In total, 250 subjects participated. Only one knee per subject was included. When both or none of the knees were affected, one knee was randomly selected for analysis. OA prevalence, sensitivity, specificity, positive and negative predictive values, and accuracy were presented (CI 95%; α = 5%)., Results: The mean age was 56.1 years (SD = 8.7), 48.8% female, and 39.2% presented knee OA according to the rheumatologist. The sensitivity and the specificity of radiographic OA were 51% and 96.7%, respectively, while the NICE definition showed 57.0% and 76.3%, respectively. The other OA criteria showed good levels of specificity, but the levels of sensitivity were below 30%. Considering NICE and/or X-ray result in combination, the sensitivity increased (73.4%), while the specificity reduced slightly (73.0%) in relation to the original NICE definition., Conclusions: Radiographic OA showed the best performance, followed by NICE definition, especially in combination with X-ray results.

Purpose: The purpose of this study was to assess body weight and periodontal disease development in obese and normal weight children., Methods: Eighty-eight 5- to 10-year-old children participated in this study. Periodontal measurements included the visible plaque index (VPI), community periodontal index (CPI), and bleeding on probing (BOP). Complete periodontal examinations were performed in some children with CPI codes three and four. Anthropometric examination consisted of body mass index (BMI, kg/m2), which was adjusted by age according to percentiles. The groups were divided into children of normal weight (N=43, BMI less than 85 per age) and obese children (N=45, BMI greater than 97 per age)., Results: The results showed that the obesity group showed significant proportions of CPI codes one (44.2%) and three (7.4%), when compared with normal weight subjects (P<0.05). VPI was similar between both groups (P>0.05). BOP was higher in obese patients than in children with normal weight (P<0.05). CPI zero was more prevalent in normal weight subjects (62.6%, P<0.05)., Conclusion: Obese children seem to be more susceptible to periodontal disease.

The nucleation of atmospheric vapours is an important source of new aerosol particles that can subsequently grow to form cloud condensation nuclei in the atmosphere. Most field studies of atmospheric aerosols over continents are influenced by atmospheric vapours of anthropogenic origin (for example, ref. 2) and, in consequence, aerosol processes in pristine, terrestrial environments remain poorly understood. The Amazon rainforest is one of the few continental regions where aerosol particles and their precursors can be studied under near-natural conditions, but the origin of small aerosol particles that grow into cloud condensation nuclei in the Amazon boundary layer remains unclear. Here we present aircraft- and ground-based measurements under clean conditions during the wet season in the central Amazon basin. We find that high concentrations of small aerosol particles (with diameters of less than 50 nanometres) in the lower free troposphere are transported from the free troposphere into the boundary layer during precipitation events by strong convective downdrafts and weaker downward motions in the trailing stratiform region. This rapid vertical transport can help to maintain the population of particles in the pristine Amazon boundary layer, and may therefore influence cloud properties and climate under natural conditions.

We assessed the effects of guaraná (Paullinia cupana) consumption on plasma catechins, erythrocyte antioxidant enzyme activity (superoxide dismutase, catalase and glutathione peroxidase) and biomarkers of oxidative stress (ex vivo LDL oxidation, plasma total antioxidant status and ORAC, and lymphocyte single cell gel electrophoresis) in healthy overweight subjects. Twelve participants completed a 15-day run-in period followed by a 15-day intervention with a daily intake of 3 g guaraná seed powder containing 90 mg (+)-catechin and 60 mg (-)-epicatechin. Blood samples were taken on the first and last day of the intervention period, fasting and 1 h post-dose. The administration of guaraná increased plasma ORAC, while reducing ex vivo LDL oxidation (only in the first study day) and hydrogen peroxide-induced DNA damage in lymphocytes, at 1 h post-dose. Plasma catechin (0.38 ± 0.12 and 0.44 ± 0.18 nmol mL(-1)), epicatechin (0.59 ± 0.18 and 0.64 ± 0.25 nmol mL(-1)) and their methylated metabolites were observed at 1 h post-dose but were almost negligible after overnight fasting. The activities of catalase (in both study days) and glutathione peroxidase (in the last intervention day) increased at 1 h post-dose. Furthermore, the activity of both enzymes remained higher than the basal levels in overnight-fasting individuals on the last intervention day, suggesting a prolonged effect of guaraná that continues even after plasma catechin clearance. In conclusion, guaraná catechins are bioavailable and contribute to reduce the oxidative stress of clinically healthy individuals, by direct antioxidant action of the absorbed phytochemicals and up-regulation of antioxidant/detoxifying enzymes.

Background: Health-related control and self-efficacy beliefs can be assessed in the general population using Multidimensional Health Locus of Control-A subscales (MHLC-A) and the General Self-Efficacy Scale (GSES), respectively., Objective: To test construct validity, internal consistency, reliability (test-retest) and ceiling and floor effects of Portuguese-Brazil versions of MHLC-A and GSES., Method: Civil servants (N=2901) enrolled in a large Brazilian cohort were included. A new version of the GSES was produced (GSES-Brazil). Procedures for cross-cultural adaptation and testing of psychometric properties followed well-accepted international guidelines., Results: Confirmatory factor analyses yielded the following indices: MHLC-A (tridimensional model): χ2[df]=223.45[132], p-value <0.01; CFI=0.87; TLI=0.85; RMSEA=0.07 (0.07-0.08); WRMR=3.00. GSES-Brazil (unidimensional model): χ2[df]=788.60[35], p-value <0.01; CFI=0.95; TLI=0.94; RMSEA=0.09 (0.08-0.09); WRMR=2.50. Cronbach's alpha coefficients and Intraclass Correlation Coefficients (ICC2,1) ranged from 0.57 (0.54-0.59) and 0.57 (0.47-0.65) for MHLC-A internality to 0.80 (0.79-0.81) and 0.71 (0.66-0.77) for GSES-Brazil, respectively. There was no evidence of ceiling and floor effects. Convergent validity analyses provided further support for construct validity of both scales., Conclusion: These findings support the use of the newly developed version of GSES-Brazil for the assessment of general self-efficacy of adult Brazilians. Internal consistency was lower than ideal for MHLC-A, indicating these subscales may need further refinements to provide a more psychometrically sound measure of control beliefs.

The aim of this study was to systematically review the prognosis of autotransplanted teeth followed up for a period of 6 years or more. A literature search was conducted in five databases and the eligibility criteria were established. The outcomes evaluated were the survival rate, percentage of abnormal mobility, pulpal conditions, and percentage of root resorption. The searches identified 1848 articles, and after evaluation against the eligibility criteria, six were included. Data related to outcome measures were extracted from the studies and a meta-analysis was performed. Survival rates ranged from 75.3% to 91% and the meta-analysis showed an effect size of 81% (P<0.0001). The percentage ankylosis ranged from 4.2% to 18.2% and the effect size was 4.8% (P<0.0001). Root resorption percentages ranged from 3% to 10% and the effect size was equal to 4% (P<0.0001). It was not possible to perform a meta-analysis of data on pulpal conditions and percentage of teeth with abnormal mobility. The results of this study showed the survival rate to be excellent, considering the observation period. The rates of ankylosis and root resorption, despite their low values, influence the prognosis of transplanted teeth., (Copyright © 2015 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

In this study, the methotrexate (MTX) was incorporated into the poly(e-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-a and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3731-3742, 2015., (Copyright © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)

Background: The investigation of stable coronary artery disease (CAD) and its treatment depend on risk stratification for decision-making on the need for cardiac catheterization and revascularization., Objective: To analyze the procedures used in the diagnosis and invasive treatment of patients with CAD, at the Brazilian Unified Health System (SUS) in the cities of Curitiba, São Paulo and at InCor-FMUSP., Methods: Retrospective, descriptive, observational study of the diagnostic and therapeutic itineraries of the Brazilian public health care system patient, between groups submitted or not to prior noninvasive tests to invasive cardiac catheterization. Stress testing, stress echocardiography, perfusion scintigraphy, catheterization and percutaneous or surgical revascularization treatment procedures were quantified and the economic impact of the used strategies., Results: There are significant differences in the assessment of patients with suspected or known CAD in the metropolitan region in the three scenarios. Although functional testing procedures are most often used the direct costs of these procedures differ significantly (6.1% in Curitiba, 20% in São Paulo and 27% in InCor-FMUSP). Costs related to the procedures and invasive treatments represent 59.7% of the direct costs of SUS in São Paulo and 87.2% in Curitiba. In InCor-FMUSP, only 24.3% of patients with stable CAD submitted to CABG underwent a noninvasive test before the procedure., Conclusion: Although noninvasive functional tests are the ones most often requested for the assessment of patients with suspected or known CAD most of the costs are related to invasive procedures/treatments. In most revascularized patients, the documentation of ischemic burden was not performed by SUS.

Trichilemmoma is a benign neoplasm from the outer sheath of the pilosebaceous follicle. Desmoplastic trichilemmoma, a rare variant, is histologically characterized by a central area of desmoplasia that can clinically mimic an invasive carcinoma, requiring histopathological examination to define the diagnosis.

There is a very well known correlation between diabetes and cardiovascular disease but many health care professionals are just concerned with glycemic control, ignoring the paramount importance of controlling other risk factors involved in the pathogenesis of serious cardiovascular diseases. This Position Statement from the Brazilian Diabetes Society was developed to promote increased awareness in relation to six crucial topics dealing with diabetes and cardiovascular disease: Glicemic Control, Cardiovascular Risk Stratification and Screening Coronary Artery Disease, Treatment of Dyslipidemia, Hypertension, Antiplatelet Therapy and Myocardial Revascularization. The issue of what would be the best algorithm for the use of statins in diabetic patients received a special attention and a new Brazilian algorithm was developed by our editorial committee. This document contains 38 recommendations which were classified by their levels of evidence (A, B, C and D). The Editorial Committee included 22 specialists with recognized expertise in diabetes and cardiology.

Background: Drug interaction studies selecting patients in a real-life setting are scarce, and most studies to date are characterized by a small sample size., Objective: To evaluate the effect of amiodarone on warfarin maintenance dose and adverse events in an anticoagulation cohort from a tertiary cardiovascular service., Methods: This study recruited 866 patients, and oral anticoagulant therapy was monitored by the prothrombin time expressed as the international normalized ratio (INR). Genotyping of CYP2C9*2, CYP2C9*3, and VKORC1 3673 polymorphisms was performed., Results: Of the 866 patients, 111 (12.8%) were taking amiodarone and warfarin simultaneously, and 514 (59.4%) reached the therapeutic target dose. The warfarin maintenance dose was significantly lower in patients simultaneously using amiodarone (23.8 ± 11.3 mg/wk) compared with other patients (29.5 ± 14.3 mg/wk; P < 0.001). Patients taking amiodarone had higher INR/current dose ratios (0.83 ± 0.04 per mg) compared with patients not using amiodarone (0.71 ± 0.02 per mg, P = 0.001). Adverse event frequency was not different between the groups (P = 0.40). No genotype effect was noted on the odds of bleeding associated with amiodarone use., Conclusions: Simultaneous use of amiodarone influences warfarin maintenance dose, but is not associated with adverse events.

The techniques used for diagnosis of canine visceral leishmaniasis (CVL) in Brazil ELISA and IFAT have been extensively questioned because of the accuracy of these tests. A recent change in the diagnosis protocol excluded IFAT and included the Dual-Path Platform (DPP). We evaluated the prevalence and incidence rates of Leishmania spp. before and after the change in the protocol. In addition, based on our results, we propose a new alternative that is less expensive for the screening and confirmation of CVL. Plasma samples were obtained from a serobank from dogs evaluated in a cross-sectional study (1,226 dogs) and in a cohort study of susceptible animals (n = 447), followed for 26 months. Serology testing was performed using ELISA, IFAT, and DPP. The incidence and prevalence of CVL were determined by using the protocol of the Visceral Leishmaniasis Control and Surveillance Program until 2012 (ELISA and IFAT using filter paper) and the protocol used after 2012 (DPP and ELISA using plasma). The prevalence was 6.2% and the incidence was 2.8 per 1,000 dog-months for the protocol used until 2012. For the new diagnosis protocol for CVL resulted in an incidence of 5.4 per 1,000 dog-months and a prevalence of 8.1%. Our results showed that the prevalence and incidence of infection were far greater than suggested by the previously used protocol and that the magnitude of infection in endemic areas has been underestimated. As tests are performed sequentially and euthanasia of dogs is carried out when the serological results are positive in both tests, the sequence does not affect the number of animals to be eliminated by the Control Program. Then we suggest to municipalities with a large demand of exams to use ELISA for screening and DPP for confirmation, since this allows easier performance and reduced cost.

Background: Renal transplant candidates are at high risk of coronary artery disease (CAD). We sought to develop a new risk score model to determine the pre-test probability of the occurrence of significant CAD in renal transplant candidates., Methods: A total of 1,060 renal transplant candidates underwent a comprehensive cardiovascular risk evaluation. Patients considered at high risk of CAD (age ≥50 years, with either diabetes mellitus (DM) or cardiovascular disease (CVD)), or having noninvasive testing suggestive of CAD were referred for coronary angiography (n = 524). Significant CAD was defined by the presence of luminal stenosis ≥70%. A binary logistic regression model was built, and the resulting logistic regression coefficient B for each variable was multiplied by 10 and rounded to the next whole number. For each patient, a corresponding risk score was calculated and the receiver operating characteristic (ROC) curve was constructed., Results: The final equation for the model was risk score = (age × 0.4) + (DM × 9) + (CVD × 14) and for the probability of CAD (%) = (risk score × 2) - 23. The corresponding ROC for the accuracy of the diagnosis of CAD was 0.75 (P <0.0001) in the developmental model., Conclusions: We developed a simple clinical risk score to determine the pre-test probability of significant CAD in renal transplant candidates. This model may help those directly involved in the care of patients with end-stage renal disease being considered for transplantation in an attempt to reduce the rate of cardiovascular events that presently hampers the long-term prognosis of such patients.

Background: We evaluated whether the advantages conferred by renal transplantation encompass all individuals or whether they favor more specific groups of patients., Methods: One thousand and fifty-eight patients on the transplant waiting list and 270 receiving renal transplant were studied. End points were the composite incidence of CV events and death. Patients were followed up from date of placement on the list until transplantation, CV event, or death (dialysis patients), or from the date of transplantation, CV event, return to dialysis, or death (transplant patients)., Results: Younger patients with no comorbidities had a lower incidence of CV events and death independently of the treatment modality (log-rank=0.0001). Renal transplantation was associated with better prognosis only in high-risk patients (p=0.003)., Conclusions: Age and comorbidities influenced the prevalence of CV complications and death independently of the treatment modality. A positive effect of renal transplantation was documented only in high-risk patients. These findings suggest that age and comorbidities should be considered indication for early transplantation even considering that, as a group, such patients have a shorter survival compared with low-risk individuals., (© 2012 John Wiley & Sons A/S.)

We compared the effects of medium light roast (MLR) and medium roast (MR) paper-filtered coffee on antioxidant capacity and lipid peroxidation in healthy volunteers. In a randomized crossover study, 20 volunteers consumed 482 ± 61 ml/day of MLR or MR for four weeks. Plasma total antioxidant status (TAS), oxygen radical absorbance capacity (ORAC), oxidized LDL and 8-epi-prostaglandin F2α, erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activity were measured at baseline and after the interventions. MLR had higher chlorogenic acids-(CGA; 334 mg/150 mL) and less caffeine (231 mg/150 ml) than MR had (210 and 244 mg/150 ml, respectively). MLR also had fewer Maillard reaction products (MRP) than MR had. Compared with baseline, subjects had an increase of 21 and 26 % in TAS, 13 and 13 % in CAT, 52 and 75 % in SOD, and 62 and 49 % in GPx after MLR and MR consumption (P < 0.001), respectively. ORAC increased after MLR (P = 0.004). No significant alteration in lipid peroxidation biomarkers was observed. Both coffees had antioxidant effects. Although MLR contained more CGA, there were similar antioxidant effects between the treatments. MRP may have contributed as an antioxidant. These effects may be important in protecting biological systems and reducing the risk of diseases related to oxidative stress.