Universidade Federal do Estado do Rio de Janeiro

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. \n \nFor example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. \n \nHere, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

Inland waters (lakes, reservoirs, streams, and rivers) are often substantial methane (CH(4)) sources in the terrestrial landscape. They are, however, not yet well integrated in global greenhouse gas (GHG) budgets. Data from 474 freshwater ecosystems and the most recent global water area estimates indicate that freshwaters emit at least 103 teragrams of CH(4) year(-1), corresponding to 0.65 petagrams of C as carbon dioxide (CO(2)) equivalents year(-1), offsetting 25% of the estimated land carbon sink. Thus, the continental GHG sink may be considerably overestimated, and freshwaters need to be recognized as important in the global carbon cycle.

Logistic regression is used to obtain odds ratio in the presence of more than one explanatory variable. The procedure is quite similar to multiple linear regression, with the exception that the response variable is binomial. The result is the impact of each variable on the odds ratio of the observed event of interest. The main advantage is to avoid confounding effects by analyzing the association of all variables together. In this article, we explain the logistic regression procedure using examples to make it as simple as possible. After definition of the technique, the basic interpretation of the results is highlighted and then some special issues are discussed.

Nota: Estas diretrizes se prestam a informar e não a substituir o julgamento clínico do médico que, em última análise, deve determinar o tratamento apropriado para seus pacientes.

Drug concentrations associated with protection from HIV-1 acquisition have not been determined. We evaluated drug concentrations among men who have sex with men in a substudy of the iPrEx trial (1). In this randomized placebo-controlled trial, daily oral doses of emtricitabine/tenofovir disoproxil fumarate were used as pre-exposure prophylaxis (PrEP) in men who have sex with men. Drug was detected less frequently in blood plasma and in viable cryopreserved peripheral blood mononuclear cells (PBMCs) in HIV-infected cases at the visit when HIV was first discovered compared with controls at the matched time point of the study (8% versus 44%; P < 0.001) and in the 90 days before that visit (11% versus 51%; P < 0.001). An intracellular concentration of the active form of tenofovir, tenofovir-diphosphate (TFV-DP), of 16 fmol per million PBMCs was associated with a 90% reduction in HIV acquisition relative to the placebo arm. Directly observed dosing in a separate study, the STRAND trial, yielded TFV-DP concentrations that, when analyzed according to the iPrEx model, corresponded to an HIV-1 risk reduction of 76% for two doses per week, 96% for four doses per week, and 99% for seven doses per week. Prophylactic benefits were observed over a range of doses and drug concentrations, suggesting ways to optimize PrEP regimens for this population.

The CMS apparatus was identified, a few years before the start of the LHC operation at CERN, to feature properties well suited to particle-flow (PF) reconstruction: a highly-segmented tracker, a fine-grained electromagnetic calorimeter, a hermetic hadron calorimeter, a strong magnetic field, and an excellent muon spectrometer.A fully-fledged PF reconstruction algorithm tuned to the CMS detector was therefore developed and has been consistently used in physics analyses for the first time at a hadron collider.For each collision, the comprehensive list of final-state particles identified and reconstructed by the algorithm provides a global event description that leads to unprecedented CMS performance for jet and hadronic τ decay reconstruction, missing transverse momentum determination, and electron and muon identification.This approach also allows particles from pileup interactions to be identified and enables efficient pileup mitigation methods.The data collected by CMS at a centre-of-mass energy of 8 TeV show excellent agreement with the simulation and confirm the superior PF performance at least up to an average of 20 pileup interactions.

Results on two-particle angular correlations for charged particles emitted in proton-proton collisions at center-of-mass energies of 0.9, 2.36, and 7 TeV are presented, using data collected with the CMS detector over a broad range of pseudorapidity (η) and azimuthal angle (φ).Short-range correlations in ∆η, which are studied in minimum bias events, are characterized using a simple "independent cluster" parametrization in order to quantify their strength (cluster size) and their extent in η (cluster decay width).Long-range azimuthal correlations are studied differentially as a function of charged particle multiplicity and particle transverse momentum using a 980 nb -1 data set at 7 TeV.In high multiplicity events, a pronounced structure emerges in the two-dimensional correlation function for particle pairs with intermediate p T of 1-3 GeV/c, 2.0 < |∆η| < 4.8 and ∆φ ≈0.This is the first observation of such a long-range, near-side feature in two-particle correlation functions in pp or pp collisions.

Systematic literature review (SLR) is a well-known research method. However, there is a paucity of detailed SLR guidelines in operations management (OM). The recent interest in SLR in OM has not been followed by the same rigour observed in disciplines as medical sciences and public policy. There are no OM-specific SLR protocols, detailed step-by-step methods and reporting procedures. Therefore, this paper provides a step-by-step approach to SLR for OM scholars and an overview of SLR’s evolution as a research method in OM and the resulting progression of themes. The step-by-step approach aims to serve as a guideline sufficiently broad to avoid skipping any significant step, but still being easy to be understood and applied. The paper describes procedures for rigourous SLR, reveals a growing use of literature review in OM, specially for qualitative SLR and traditional narrative reviews, assesses contemporary and emerging themes in OM, and provides a research agenda.

Department of Economics and Statistics, University of Naples Federico II, Italy. info@bibliometrix.org; https://www.bibliometrix.org/; free, donations accepted.

A bstract A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 fb −1 at $ \sqrt{s}=7 $ TeV, and up to 5.3 fb −1 at $ \sqrt{s}=8 $ TeV . The results for five Higgs boson decay modes γγ , ZZ, WW, ττ , and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, γγ and ZZ → 4 ℓ , gives a mass estimate of 125 . 3 ± 0 . 4 (stat.) ± 0 . 5 (syst.) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.

Is active restoration the best approach to achieve ecological restoration success (the return to a reference condition, that is, old-growth forest) when compared to natural regeneration in tropical forests? Our meta-analysis of 133 studies demonstrated that natural regeneration surpasses active restoration in achieving tropical forest restoration success for all three biodiversity groups (plants, birds, and invertebrates) and five measures of vegetation structure (cover, density, litter, biomass, and height) tested. Restoration success for biodiversity and vegetation structure was 34 to 56% and 19 to 56% higher in natural regeneration than in active restoration systems, respectively, after controlling for key biotic and abiotic factors (forest cover, precipitation, time elapsed since restoration started, and past disturbance). Biodiversity responses were based primarily on ecological metrics of abundance and species richness (74%), both of which take far less time to achieve restoration success than similarity and composition. This finding challenges the widely held notion that natural forest regeneration has limited conservation value and that active restoration should be the default ecological restoration strategy. The proposition that active restoration achieves greater restoration success than natural regeneration may have arisen because previous comparisons lacked controls for biotic and abiotic factors; we also did not find any difference between active restoration and natural regeneration outcomes for vegetation structure when we did not control for these factors. Future policy priorities should align the identified patterns of biophysical and ecological conditions where each or both restoration approaches are more successful, cost-effective, and compatible with socioeconomic incentives for tropical forest restoration.

Combined results are reported from searches for the standard model Higgs boson in proton-proton collisions at √ s = 7 TeV in five Higgs boson decay modes: γ γ , bb, τ τ , WW, and ZZ.The explored Higgs boson mass range is 110-600 GeV.The analysed data correspond to an integrated luminosity of 4.6-4.8fb -1 .The expected excluded mass range in the absence of the standard model Higgs boson is 118-543 GeV at 95% CL.The observed results exclude the standard model Higgs boson in the mass range 127-600 GeV at 95% CL, and in the mass range 129-525 GeV at 99% CL.An excess of events above the expected standard model background is observed at the low end of the explored mass range making the observed limits weaker than expected in the absence of a signal.The largest excess, with a local significance of 3.1σ , is observed for a Higgs boson mass hypothesis of 124 GeV.The global significance of observing an excess with a local significance 3.1σ anywhere in the search range 110-600 (110-145) GeV is estimated to be 1.5σ (2.1σ ).More data are required to ascertain the origin of the observed excess.

Two billion ha have been identified globally for forest restoration. Our meta-analysis encompassing 221 study landscapes worldwide reveals forest restoration enhances biodiversity by 15-84% and vegetation structure by 36-77%, compared with degraded ecosystems. For the first time, we identify the main ecological drivers of forest restoration success (defined as a return to a reference condition, that is, old-growth forest) at both the local and landscape scale. These are as follows: the time elapsed since restoration began, disturbance type and landscape context. The time elapsed since restoration began strongly drives restoration success in secondary forests, but not in selectively logged forests (which are more ecologically similar to reference systems). Landscape restoration will be most successful when previous disturbance is less intensive and habitat is less fragmented in the landscape. Restoration does not result in full recovery of biodiversity and vegetation structure, but can complement old-growth forests if there is sufficient time for ecological succession.

Roads fragment landscapes and trigger human colonization and degradation of ecosystems, to the detriment of biodiversity and ecosystem functions. The planet's remaining large and ecologically important tracts of roadless areas sustain key refugia for biodiversity and provide globally relevant ecosystem services. Applying a 1-kilometer buffer to all roads, we present a global map of roadless areas and an assessment of their status, quality, and extent of coverage by protected areas. About 80% of Earth's terrestrial surface remains roadless, but this area is fragmented into ~600,000 patches, more than half of which are <1 square kilometer and only 7% of which are larger than 100 square kilometers. Global protection of ecologically valuable roadless areas is inadequate. International recognition and protection of roadless areas is urgently needed to halt their continued loss.

In this international study, we examined the incidence of hip fractures, postfracture treatment, and all-cause mortality following hip fractures, based on demographics, geography, and calendar year. We used patient-level healthcare data from 19 countries and regions to identify patients aged 50 years and older hospitalized with a hip fracture from 2005 to 2018. The age- and sex-standardized incidence rates of hip fractures, post-hip fracture treatment (defined as the proportion of patients receiving anti-osteoporosis medication with various mechanisms of action [bisphosphonates, denosumab, raloxifene, strontium ranelate, or teriparatide] following a hip fracture), and the all-cause mortality rates after hip fractures were estimated using a standardized protocol and common data model. The number of hip fractures in 2050 was projected based on trends in the incidence and estimated future population demographics. In total, 4,115,046 hip fractures were identified from 20 databases. The reported age- and sex-standardized incidence rates of hip fractures ranged from 95.1 (95% confidence interval [CI] 94.8-95.4) in Brazil to 315.9 (95% CI 314.0-317.7) in Denmark per 100,000 population. Incidence rates decreased over the study period in most countries; however, the estimated total annual number of hip fractures nearly doubled from 2018 to 2050. Within 1 year following a hip fracture, post-hip fracture treatment ranged from 11.5% (95% CI 11.1% to 11.9%) in Germany to 50.3% (95% CI 50.0% to 50.7%) in the United Kingdom, and all-cause mortality rates ranged from 14.4% (95% CI 14.0% to 14.8%) in Singapore to 28.3% (95% CI 28.0% to 28.6%) in the United Kingdom. Males had lower use of anti-osteoporosis medication than females, higher rates of all-cause mortality, and a larger increase in the projected number of hip fractures by 2050. Substantial variations exist in the global epidemiology of hip fractures and postfracture outcomes. Our findings inform possible actions to reduce the projected public health burden of osteoporotic fractures among the aging population. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Drosophila melanogaster plays an important role in molecular, genetic, and genomic studies of heredity, development, metabolism, behavior, and human disease. The initial reference genome sequence reported more than a decade ago had a profound impact on progress in Drosophila research, and improving the accuracy and completeness of this sequence continues to be important to further progress. We previously described improvement of the 117-Mb sequence in the euchromatic portion of the genome and 21 Mb in the heterochromatic portion, using a whole-genome shotgun assembly, BAC physical mapping, and clone-based finishing. Here, we report an improved reference sequence of the single-copy and middle-repetitive regions of the genome, produced using cytogenetic mapping to mitotic and polytene chromosomes, clone-based finishing and BAC fingerprint verification, ordering of scaffolds by alignment to cDNA sequences, incorporation of other map and sequence data, and validation by whole-genome optical restriction mapping. These data substantially improve the accuracy and completeness of the reference sequence and the order and orientation of sequence scaffolds into chromosome arm assemblies. Representation of the Y chromosome and other heterochromatic regions is particularly improved. The new 143.9-Mb reference sequence, designated Release 6, effectively exhausts clone-based technologies for mapping and sequencing. Highly repeat-rich regions, including large satellite blocks and functional elements such as the ribosomal RNA genes and the centromeres, are largely inaccessible to current sequencing and assembly methods and remain poorly represented. Further significant improvements will require sequencing technologies that do not depend on molecular cloning and that produce very long reads.

OBJECTIVE To assess the impact of consuming ultra-processed foods on the nutritional dietary profile in Brazil. METHODS Cross-sectional study conducted with data from the module on individual food consumption from the 2008-2009 Pesquisa de Orçamentos Familiares (POF - Brazilian Family Budgets Survey). The sample, which represented the section of the Brazilian population aged 10 years or over, involved 32,898 individuals. Food consumption was evaluated by two 24-hour food records. The consumed food items were classified into three groups: natural or minimally processed, including culinary preparations with these foods used as a base; processed; and ultra-processed. RESULTS The average daily energy consumption per capita was 1,866 kcal, with 69.5% being provided by natural or minimally processed foods, 9.0% by processed foods and 21.5% by ultra-processed food. The nutritional profile of the fraction of ultra-processed food consumption showed higher energy density, higher overall fat content, higher saturated and trans fat, higher levels of free sugar and less fiber, protein, sodium and potassium, when compared to the fraction of consumption related to natural or minimally processed foods. Ultra-processed foods presented generally unfavorable characteristics when compared to processed foods. Greater inclusion of ultra-processed foods in the diet resulted in a general deterioration in the dietary nutritional profile. The indicators of the nutritional dietary profile of Brazilians who consumed less ultra-processed foods, with the exception of sodium, are the stratum of the population closer to international recommendations for a healthy diet. CONCLUSIONS The results from this study highlight the damage to health that is arising based on the observed trend in Brazil of replacing traditional meals, based on natural or minimally processed foods, with ultra-processed foods. These results also support the recommendation of avoiding the consumption of these kinds of foods.

Cardiovascular diseases are the most prevalent cause of morbidity and mortality among patients with type 1 or type 2 diabetes. The proposed mechanisms that can link accelerated atherosclerosis and increased cardiovascular risk in this population are poorly understood. It has been suggested that an association between hyperglycemia and intracellular metabolic changes can result in oxidative stress, low-grade inflammation, and endothelial dysfunction. Recently, epigenetic factors by different types of reactions are known to be responsible for the interaction between genes and environment and for this reason can also account for the association between diabetes and cardiovascular disease. The impact of clinical factors that may coexist with diabetes such as obesity, dyslipidemia, and hypertension are also discussed. Furthermore, evidence that justify screening for subclinical atherosclerosis in asymptomatic patients is controversial and is also matter of this review. The purpose of this paper is to describe the association between poor glycemic control, oxidative stress, markers of insulin resistance, and of low-grade inflammation that have been suggested as putative factors linking diabetes and cardiovascular disease.

The current standard of care for newly diagnosed cases of high-grade glioma is surgical resection followed by RT with concurrent chemotherapy. The most widely used criteria for assessing treatment response are based on a 2D measurement of the enhancing area on MR imaging known as the Macdonald Criteria. Recently, nontumoral increases (pseudoprogression) and decreases (pseudoresponse) in enhancement have been found, and these can confuse outcome evaluation. Here we review pseudoprogression and pseudoresponse and describe how better understanding of these phenomena can aid interpretation.

Given the importance of bacteria in the development of periradicular lesions, the eradication of the root canal infection is paramount in endodontic treatment. This study evaluated the in vitro intracanal bacterial reduction produced by instrumentation and irrigation with 1%, 2.5%, and 5.25% sodium hypochlorite (NaOCl) or saline solution. Root canals inoculated with Enterococcus faecalis were instrumented and irrigated with the solutions tested. Canals were sampled before and after preparation. After serial dilution, samples were plated onto Mitis salivarius agar, and the colony-forming units grown were counted. Inhibitory effects of the three NaOCl solutions on E. faecalis were also evaluated by means of the agar diffusion test. All test solutions significantly reduced the number of bacterial cells in the root canal (p < 0.05). There was no significant difference between the three NaOCl solutions tested (p > 0.05). Nonetheless, all NaOCl solutions were significantly more effective than saline solution in reducing the number of bacterial cells within the root canal (p < 0.05). The three NaOCl concentrations showed large zones of inhibition against E. faecalis. The results of this study suggest that regular exchange and the use of large amounts of irrigant should maintain the antibacterial effectiveness of the NaOCl solution, compensating for the effects of concentration.