Efficacy of a radiographic film holder adapter in generating radiographs of dental implants with improved geometric accuracy and sharpness.

STATEMENT OF PROBLEM: Some radiographic film holders produce radiographs with geometric distortion that may interfere with diagnosis. However, whether the distortion can be corrected by adjusting the design of the radiographic film holder is unclear. PURPOSE: The purpose of the study was to develop an adapter for a radiographic film holder model aiming to generate radiographs with greater sharpness and a more accurate geometric representation of dental implants. MATERIAL AND METHODS: The 2-piece adapter was designed using the SketchUp software program and was 3-dimensionally (3D) printed. Implants with internal conical connections were installed in 19 maxillary prototypes in the central incisor region. Five dentists obtained 285 digital periapical radiographs with 3 different radiographic film holders: standard Cone Indicator, Rinn XCP, and adapted Cone Indicator. They then evaluated the radiographic sharpness of the implants threads and their dimensions using the ImageJ software program. The data were analyzed using the Friedman test with the Durbin-Conover post hoc test and MANOVA with the Tukey post hoc test (α=.05). RESULTS: On the mesial surface of the implants, the threads were sharper for the adapted than for the standard Cone Indicator radiographic film holder (P<.05). The adapted Cone Indicator showed a smaller difference between the radiographic and actual implant diameters compared with the Rinn XCP and standard Cone Indicator radiographic film holders (P<.05). CONCLUSIONS: The developed adapter provided radiographs of dental implants with improved sharpness and geometric accuracy.

Genomic analysis of genotype-environment interaction in age at first calving of Murrah buffaloes.

Age at first calving (AFC) is a measure of sexual maturity associated with the start of productive life of dairy animals. Additionally, a lower AFC reduces the generation interval and early culling of females. However, AFC has low heritability, making it a trait highly influenced by environmental factors. In this scenario, one way to improve the reproductive performance of buffalo cows is to select robust animals according to estimated breeding value (EBV) using models that include genotype-environment interaction (GEI) with the application of reaction norm models (RNMs). This can be achieved by understanding the genomic basis related to GEI of AFC. Thus, in this study, we aimed to predict EBV considering GEI via the RNM and identify candidate genes related to this component in dairy buffaloes through genome-wide association studies (GWAS). We used 1795 AFC records from three Murrah buffalo herds and formed environmental gradients (EGs) from contemporary group solutions obtained from genetic analysis of 270-day cumulative milk yield. Heritability estimates ranged from 0.15 to 0.39 along the EG. GWAS of the RNM slope parameter identified important genomic regions. The genomic window that explained the highest percentage of genetic variance of the slope (0.67%) was located on BBU1. After functional analysis, five candidate genes were detected, involved in two biological processes. The results suggested the existence of a GEI for AFC in Murrah buffaloes, with reclassification of animals when different environmental conditions were considered. The inclusion of genomic information increased the accuracy of breeding values for the intercept and slope of the reaction norm. GWAS analysis suggested that important genes associated with the AFC reaction norm slope were possibly also involved in biological processes related to lipid metabolism and immunity.

Effects of bariatric surgery on renal function: a retrospective cohort study comparing one-year outcomes between one-anastomosis gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Evidence on the effect of one-anastomosis gastric bypass (OAGB) on renal function is limited. OBJECTIVE: To compare the evolution of estimated renal function observed 1 year after OAGB and Roux-en-Y gastric bypass (RYGB) in individuals with obesity. DESIGN AND SETTING: Observational, analytical, and retrospective cohort study. Tertiary-level university hospital. METHODS: This study used a prospectively collected database of individuals who consecutively underwent bariatric surgery. Renal function was assessed by calculating the estimated glomerular filtration rate (eGFR), according to the Chronic Kidney Disease Epidemiology Collaboration. The one-year variation in the eGFR was compared between the procedures. RESULTS: No significant differences in age, sex, obesity-associated conditions, or body mass index were observed among individuals who underwent either OAGB or RYGB. OAGB led to a significantly higher percentage of total (P = 0.007) and excess weight loss (P = 0.026). Both OAGB and RYGB led to significantly higher values of eGFR (103.9 ± 22 versus 116.1 ± 13.3; P = 0.007, and 102.4 ± 19 versus 113.2 ± 13.3; P < 0.001, respectively). The one-year variation in eGFR was 11 ± 16.2% after OAGB and 16.7 ± 26.3% after RYGB (P = 0.3). Younger age and lower baseline eGFR were independently associated with greater postoperative improvement in renal function (P < 0.001). CONCLUSION: Compared with RYGB, OAGB led to an equivalent improvement in renal function 1 year after the procedure, along with greater weight loss.

Automatic mapping of high-risk urban areas for Aedes aegypti infestation based on building facade image analysis.

BACKGROUND: Dengue, Zika, and chikungunya, whose viruses are transmitted mainly by Aedes aegypti, significantly impact human health worldwide. Despite the recent development of promising vaccines against the dengue virus, controlling these arbovirus diseases still depends on mosquito surveillance and control. Nonetheless, several studies have shown that these measures are not sufficiently effective or ineffective. Identifying higher-risk areas in a municipality and directing control efforts towards them could improve it. One tool for this is the premise condition index (PCI); however, its measure requires visiting all buildings. We propose a novel approach capable of predicting the PCI based on facade street-level images, which we call PCINet. METHODOLOGY: Our study was conducted in Campinas, a one million-inhabitant city in São Paulo, Brazil. We surveyed 200 blocks, visited their buildings, and measured the three traditional PCI components (building and backyard conditions and shading), the facade conditions (taking pictures of them), and other characteristics. We trained a deep neural network with the pictures taken, creating a computational model that can predict buildings' conditions based on the view of their facades. We evaluated PCINet in a scenario emulating a real large-scale situation, where the model could be deployed to automatically monitor four regions of Campinas to identify risk areas. PRINCIPAL FINDINGS: PCINet produced reasonable results in differentiating the facade condition into three levels, and it is a scalable strategy to triage large areas. The entire process can be automated through data collection from facade data sources and inferences through PCINet. The facade conditions correlated highly with the building and backyard conditions and reasonably well with shading and backyard conditions. The use of street-level images and PCINet could help to optimize Ae. aegypti surveillance and control, reducing the number of in-person visits necessary to identify buildings, blocks, and neighborhoods at higher risk from mosquito and arbovirus diseases.

Inflammatory markers changes following acceptance-based behavioral psychotherapy in generalized anxiety disorder patients: Evidence from a randomized controlled trial.

Introduction: Generalized anxiety disorder (GAD) has been associated with elevated levels of C-reactive protein (CRP) and proinflammatory cytokines. Despite robust evidence as an effective treatment for GAD, research on the effects of cognitive-behavioral therapies (CBT) in the inflammatory profile of patients with clinical anxiety has presented mixed results. Objective: The present study aimed to investigate the effect of an acceptance-based behavior therapy (ABBT) on inflammatory biomarkers and their association with anxiety levels in GAD patients in comparison to supportive therapy as an active control. Methods: Peripheral inflammatory biomarkers (CRP, IL-1ß, IL-4, IL-6, IL-10, TNF-α) were measured in 77 GAD patients who participated in a 14-week 10-session randomized clinical trial of group ABBT (experimental, n = 37) or supportive group therapy (ST: active control group, n = 40). Results: The concentrations of IL-1ß decreased in the control group and the concentrations of IL-6 increased in the experimental group from baseline to post-treatment, whereas no difference was identified in IL-4, IL-10, TNF, or CRP. Although anxiety and depression levels decreased in both treatment conditions, no correlation with inflammation markers was found for most clinical and biological variables. A negative correlation between changes in IL-6 and IL-10 and anxiety symptom score changes was identified. Conclusions: The present study results found that a short trial of acceptance-based behavior therapy did not change the proinflammatory profile which may be associated with GAD. Additional research is needed to evaluate the influence of other inflammation-related variables, longer periods of follow-up as well as the effect of supportive therapy on peripheral inflammatory biomarkers in GAD patients.

Qualitative transformations of street-seized ecstasy over a decade: A case study in Rio de Janeiro (Brazil).

The illegal drug market is constantly evolving, with new drugs being created and existing ones being modified. Adulterants are often added to the mix, and the primary substance may be secretly replaced by a new one. Once-known tablets can now be vastly different from what they are sold as, all due to the pursuit of profit and evasion of current drug regulations. These alterations in drug composition pose a threat to society, as their effects are still not well understood. Therefore, it is crucial for police intelligence and public health development to obtain the chemical profiles of illicit drugs. This study presents the chemical fingerprinting of ecstasy tablets seized in the state of Rio de Janeiro (Brazil) between 2012 and 2021. The tablet samples were weighed, extracted, diluted with methanol, and acidified before analysis using gas chromatography high-resolution mass spectrometry and attenuated total reflection Fourier transform infrared spectroscopy. The major constituents found were MDMA and clobenzorex, with fewer occurrences of MDA, MDEA, and 2C-B. The results also indicate that the occurrence of mega-events in the study location impacted the chemical fingerprints of ecstasy. A total of 27 combinations of cutting agents, including caffeine, ephedrine, and anesthetics, were identified. Samples composed of clobenzorex were observed throughout the evaluated period in areas near highways, suggesting that this product is mainly used by truck drivers. These findings can help police intelligence units anticipate the behavior of the illicit market during major events, identify traffic routes, and support public health initiatives.

Impaired signaling pathways on Berardinelli-Seip congenital lipodystrophy macrophages during Leishmania infantum infection.

Berardinelli-Seip congenital lipodystrophy (CGL), a rare autosomal recessive disorder, is characterized by a lack of adipose tissue. Infections are one of the major causes of CGL individuals' premature death. The mechanisms that predispose to infections are poorly understood. We used Leishmania infantum as an in vitro model of intracellular infection to explore mechanisms underlying the CGL infection processes, and to understand the impact of host mutations on Leishmania survival, since this pathogen enters macrophages through specialized membrane lipid domains. The transcriptomic profiles of both uninfected and infected monocyte-derived macrophages (MDMs) from CGL (types 1 and 2) and controls were studied. MDMs infected with L. infantum showed significantly downregulated expression of genes associated with infection-response pathways (MHC-I, TCR-CD3, and granzymes). There was a transcriptomic signature in CGL cells associated with impaired membrane trafficking and signaling in response to infection, with concomitant changes in the expression of membrane-associated genes in parasites (e.g. δ-amastins). We identified pathways suggesting the lipid storage dysfunction led to changes in phospholipids expression and impaired responses to infection, including immune synapse (antigen presentation, IFN-γ signaling, JAK/STAT); endocytosis; NF-kappaB signaling; and phosphatidylinositol biosynthesis. In summary, lipid metabolism of the host plays an important role in determining antigen presentation pathways.

Validity and reliability of My Jump 2® app to measure the vertical jump on elite women beach volleyball players.

Purpose: The aim of this study was to assess the reliability and validity of the My Jump 2® app in measuring jump height, flight time, and peak power among elite women beach volleyball players on sand surfaces. Methods: Eleven elite female beach volleyball players (aged 23.6 ± 6.2 years; weight 66.3 ± 5.8 kg; height 174.4 ± 5.8 cm; with 8.4 ± 4.8 years of professional experience) participated in this study. Each player performed six countermovement jumps in a wooden box filled with sand on a force platform while simultaneously recording a video for subsequent analysis using the My Jump 2® app. Results: We found excellent agreement for flight time, jump height and peak power between observers (ICC = 0.92, 0.91 and 0.97, respectively). No significant differences between force platform and My Jump 2® app were detected in the values obtained for the three variables (P > 0.05). For the force platform and the My Jump 2® app, we found a good agreement measuring jump height and flight time (ICC = 0.85 and 0.85, respectively). However, we only found a moderate agreement for peak power (ICC = 0.64). The difference in jump height showed a limit of agreement between -4.10 and 4.74 cm in Bland-Altman, indicating a high level of agreement between the two measurement tools. Conclusion: Based on our findings, the My Jump 2® app reveals a valid tool for measuring jump height and flight time of CMJ on sand surfaces. However, more caution is needed when measuring peak power.

Multispecies and multibiomarker assessment of fish health from Iguaçu River reservoir, Southern Brazil.

This study investigated the impact of micropollutants on fish health from Segredo hydroelectric reservoir (HRS) along the Iguaçu River, Southern Brazil, contaminated by urban, industrial, and agricultural activities. This is the first comprehensive study assessment in the river after the severe drought in the 2020s in three fish species from different trophic levels Astyanax spp. (water column depth/omnivorous), Hypostomus commersoni (demersal/herbivorous), and Pimelodus maculatus (demersal/omnivorous). Animals, water, and sediment samples were collected from three distinct sites within the reservoir: Floresta (upstream), Iratim (middle), and Station (downstream). The chemical analysis revealed elevated concentrations of metals (Al, Cu, Fe) and the metalloid As in water, or Cu, Zn, and As in sediment, surpassing Brazilian regulatory limits, while the organic pollutants as DDT, PAHs, PCBs, and PBDEs were found under the Brazilian regulatory limits. The metal bioaccumulation was higher in gills with no significant differences among sites. The species Astyanax spp. and H. commersoni displayed variations in hepatosomatic index (HSI) and P. maculatus in the condition factor index (K) between sites, while adverse effects due to micropollutants bioaccumulation were observed by biochemical, genotoxic, and histopathological biomarkers. The principal component analysis and integrated biomarker response highlighted the upstream site Floresta as particularly inhospitable for biota, with distinctions based on trophic level. Consequently, this multifaceted approach, encompassing both fish biomarkers and chemical analyses, furnishes valuable insights into the potential toxic repercussions of micropollutant exposure. These findings offer crucial data for guiding management and conservation endeavors in the Iguaçu River.

Human movement and environmental barriers shape the emergence of dengue.

Understanding how emerging infectious diseases spread within and between countries is essential to contain future pandemics. Spread to new areas requires connectivity between one or more sources and a suitable local environment, but how these two factors interact at different stages of disease emergence remains largely unknown. Further, no analytical framework exists to examine their roles. Here we develop a dynamic modelling approach for infectious diseases that explicitly models both connectivity via human movement and environmental suitability interactions. We apply it to better understand recently observed (1995-2019) patterns as well as predict past unobserved (1983-2000) and future (2020-2039) spread of dengue in Mexico and Brazil. We find that these models can accurately reconstruct long-term spread pathways, determine historical origins, and identify specific routes of invasion. We find early dengue invasion is more heavily influenced by environmental factors, resulting in patchy non-contiguous spread, while short and long-distance connectivity becomes more important in later stages. Our results have immediate practical applications for forecasting and containing the spread of dengue and emergence of new serotypes. Given current and future trends in human mobility, climate, and zoonotic spillover, understanding the interplay between connectivity and environmental suitability will be increasingly necessary to contain emerging and re-emerging pathogens.

Sensitivity and antioxidant response of forest species seedlings to the atrazine under simulated conditions of subsurface water contamination.

Atrazine is an herbicide with a high soil leaching capacity, contaminating subsurface water sources. Once the water table is contaminated, riparian species can be exposed to atrazine. In this way, understanding the impacts of this exposure must be evaluated for planning strategies that minimize the effects of this herbicide on native forest species. We aimed to evaluate forest species' sensitivity and antioxidant response to exposure to subsurface waters contaminated with atrazine, as well the dissipation this herbicide. The experiment was conducted in a greenhouse in a completely randomized design, with three replications and one plant per experimental unit. The treatments were arranged in a 2 × 10 factorial. The first factor corresponded to the presence or absence (control) of the atrazine in the subsurface water. The second factor comprised 10 forest species: Amburana cearensis, Anadenanthera macrocarpa, Bauhinia cheilantha, Enterolobium contortisiliquum, Hymenaea courbaril, Libidibia ferrea, Mimosa caesalpiniifolia, Mimosa tenuiflora, Myracrodruon urundeuva, and Tabebuia aurea. The forest species studied showed different sensitivity levels to atrazine in subsurface water. A. cearensis and B. cheilantha species do not have efficient antioxidant systems to prevent severe oxidative damage. The species A. macrocarpa, E. contortisiliquum, L. ferrea, and M. caesalpiniifolia are moderately affected by atrazine. H. courbaril, M. urundeuva, and T. aurea showed greater tolerance to atrazine due to the action of the antioxidant system of these species, avoiding membrane degradation events linked to the production of reactive oxygen species (ROS). Among the forest species, H. courbaril has the most significant remedial potential due to its greater tolerance and reduced atrazine concentrations in the soil.

Insights of potential trypanocidal effect of the synthetic derivative (2E)-1-(4-aminophenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one: in vitro assay, MEV analysis, quantum study, molecular docking, molecular dynamics, MPO analysis, and predictive ADMET.

This study aims to evaluate the antitrypanosomiasis activity of a synthetic dichloro-substituted aminochalcone via in vitro assays against infected cell cultures, as well as a theoretical characterization of pharmacokinetics and pharmacodynamics against the protein targets of the evolutionary cycle of T. cruzi. The in vitro evaluation of parasite proliferation inhibition was performed via cytotoxicity analysis on mammalian host cells, effect on epimastigote and trypomastigote forms, and cell death analysis, while computer simulations characterized the electronic structure of (2E)-1-(4-aminophenyl)-3-(2,4-dichlorophenyl)prop-2-en-1-one (DCl), the mechanism of action against the proteins of the evolutionary cycle of T. cruzi: Cruzain, Trypanothione reductase, TcGAPDH, and CYP51 by molecular docking and dynamics and predictive pharmacokinetics by MPO-based ADMET. The in vitro tests showed that the DCl LC50 in order of 178.9 ± 23.9 was similar to the BZN, evidencing the effectiveness of chalcone against Trypomastigotes. Molecular docking and dynamics simulations suggest that DCl acts on the active site of the CYP51 receptor, with hydrogen interactions that showed a high degree of occupation, establishing a stable complex with the target. MPO analysis and ADMET prediction tests suggest that the compound presents an alignment between permeability and hepatic clearance, although it presents low metabolic stability. Chalcone showed stable pharmacodynamics against the CYP51 target, but can form reactive metabolites from N-conjugation and C = C epoxidation, as an indication of controlled oral dose, although the estimated LD50 rate > 500 mg/kg is a indicative of low incidence of lethality by ingestion, constituting a promising therapeutic strategy.

Osteoporosis in Parkinson's disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center.

Background: Parkinson's disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures. Objective: This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD. Methods: We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person's 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations. Results: We evaluated 107 patients in total, of whom 45 (42%) were women. The group's mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria. Conclusion: Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD.

Characterization of teaching-learning tutors in public health services and topics of interest for their work.

OBJECTIVE: To describe the profile of teaching-learning tutors in public health services and investigate which topics are of greatest interest in development spaces for these actors. METHOD: Cross-sectional study. Eligible tutors of Health Care Planning. Data collection using an electronic questionnaire composed of closed questions on sociodemographic characteristics, training and performance. Chi-square test used to compare proportions according to tutor typologies. RESULTS: A total of 614 tutors worked in Brazil's five geographic regions, the majority in primary care (82%), followed by state/regional work (13%) and specialized outpatient care (5%). The majority reported being female, of brown skin color, from the nursing field, having worked as a tutor for less than a year, and with no previous experience in preceptorship or similar. The most important topics were Health Care Networks, risk stratification for chronic conditions and the functions of specialized outpatient care. CONCLUSION: The predominance of certain characteristics among tutors was identified, with differences between the types of work. The findings can support managers in the process of selecting and developing tutors in Health Care Planning.

Synthesis, Characterization, and Evaluation of the Antimicrobial Effects and Cytotoxicity of a Novel Nanocomposite Based on Polyamide 6 and Trimetaphosphate Nanoparticles Decorated with Silver Nanoparticles.

This study aimed to develop a polymeric matrix of polyamide-6 (P6) impregnated with trimetaphosphate (TMP) nanoparticles and silver nanoparticles (AgNPs), and to evaluate its antimicrobial activity, surface free energy, TMP and Ag+ release, and cytotoxicity for use as a support in dental tissue. The data were subjected to statistical analysis (p < 0.05). P6 can be incorporated into TMP without altering its properties. In the first three hours, Ag+ was released for all groups decorated with AgNPs, and for TMP, the release only occurred for the P6-TMP-5% and P6-TMP-10% groups. In the inhibition zones, the AgNPs showed activity against both microorganisms. The P6-TMP-2.5%-Ag and P6-TMP-5%-Ag groups with AgNPs showed a greater reduction in CFU for S. mutans. For C. albicans, all groups showed a reduction in CFU. The P6-TMP groups showed higher cell viability, regardless of time (p < 0.05). The developed P6 polymeric matrix impregnated with TMP and AgNPs demonstrated promising antimicrobial properties against the tested microorganisms, making it a potential material for applications in scaffolds in dental tissues.

Spatial analysis of American cutaneous leishmaniasis in the state of Amazonas.

OBJECTIVE: To evaluate, using spatial analysis, the occurrence of American Cutaneous Leishmaniasis (ACL) and analyze its association with the municipal human development index (MHDI) and deforestation in the state of Amazonas, Brazil, from 2016 to 2020. METHODS: This ecological study, carried out from January 2016 to December 2020, included the 62 municipalities of the state of Amazonas. The incidence rate of ACL was determined in space and time. Using Multiple Linear Regression by Ordinary Least Squares (OLS) and Spatial Autoregressive Regression (SAR) models, the relationship between incidence rates and Human Development Index (HDI) and deforestation was analyzed., The high- and low-risk clusters were identified by employing the Getis-Ord Gi* statistic. RESULTS: A total of 7,499 cases of ACL were registered in all 62 municipalities in the state. Most cases were in male (n=5,924; 79.24%), with the greatest frequency in the population aged from 20 to 39 years (n=3,356; 44.7%). The incidence rate in the state of Amazonas was 7.34 cases per 100,000 inhabitants-year, with the municipalities of Rio Preto da Eva and Presidente Figueiredo showing the highest rates (1,377.5 and 817.5 cases per 100,000 population-year, respectively). The ACL cases were clustered into specific areas related to those municipalities with the highest incidence rates. The SAR model revealed a positive relationship between ACL and deforestation. CONCLUSIONS: The occurrence of ACL was evident in a variety of patterns in the state of Amazonas; the high incidence rates and persistence of this disease in this state were linked to deforestation. The temporal distribution showed variations in the incidence rates during each year. Our results can help optimize the measures needed to prevent and control this disease in the state.

Green Enzymatic Synthesis of Geranyl Butyrate: Process Optimization and Mechanistic Insights.

Flavor esters are organic compounds widely used in the food industry to enhance the aroma and taste of products. However, most chemical processes for the production of these flavoring compounds use toxic organic solvents. Some organic solvents derived from petroleum can leave behind residual traces in food products, which may raise concerns about potential health risks and contamination. In this study, we employ Eversa Transform 2.0, a commercial lipase derived from the lipase from Thermomyces lanuginosus, to produce geranyl butyrate in aqueous media. The chemical process was optimized using the Taguchi method, and a conversion of 93% was obtained at the optimal reaction conditions of: 1:5 molar ratio (v/v), 15% biocatalyst load (w/w), at 50 °C, in 6 h. Classic (molecular dynamics) and quantum (density functional theory) simulations unveiled amino acid residues involved in the stabilization of the enzyme-substrate complex. Detailed QM/MM mechanistic studies identified the nucleophilic attack of the deacylation reaction as the rate-limiting step of the entire mechanism, which has a free energy barrier of 14.0 kcal/mol.

Depth of invasion analysis to predict acral melanoma outcomes.

BACKGROUND: Acral melanoma is a subtype with worse outcomes. The Breslow micrometric measurement is the most critical parameter in planning treatment and predicting outcomes. However, for acral lentiginous melanoma, the value of the Breslow thickness is a matter of debate. Depth of Invasion (DOI) is a well-established measure for staging oral squamous cell carcinoma. OBJECTIVE: This study compared DOI and Breslow thickness for predicting acral melanoma outcomes. METHODS: We performed a retrospective cross-sectional study of 71 acral melanoma lesions subjected to sentinel lymph node biopsy at one Brazilian referral center. RESULTS: Cox model univariate analysis showed that both DOI and Breslow thickness predicted melanoma specific survival (HR 1.12; p = 0.0255 and HR 1.144; p = 0.0006, respectively), although Kaplan Meier curve was only significant for Breslow (χ2 = 5.792; p = 0.0161) and not for DOI (χ2 = 0.2556; p = 0.6132). Sentinel lymph node status and presence or absence of ulceration also predicted specific survival in patients with acral melanoma (χ2 = 6.3514; p = 0.0117 and χ2 = 4.2793; p = 0.0386, respectively). Multivariate analysis, however, demonstrated that Breslow depth was the only independent parameter for predicting acral melanoma specific survival (HR 1.144; p = 0.0006). CONCLUSION: Even though Breslow thickness remains the main predictor for survival in acral melanoma, it is not a perfect parameter. The introduction of DOI in this context opens new perspectives for predicting acral melanoma outcomes.

Family Vulnerability Scale: validity evidence in primary health care.

OBJECTIVE: Investigate evidence of validity of the Family Vulnerability Scale (EVFAM-BR) as an instrument to support population-based management in primary health care (PHC), in the scope of Health Care Planning (PAS). METHODS: This is a psychometric study to assess any additional evidence of the internal structure of EVFAM-BR using confirmatory factor analysis (CFA) and network analysis (NA). A preliminary version of the scale with 38 items was submitted to patients of PHC facilities that use the PAS methodology, distributed across the five regions of Brazil. For the primary CFA data, factor loadings and predictive power (R2) of the item were used. Seven model adjustment indices were adopted and reliability was measured by three indicators, using Bayesian estimation. RESULTS: The preliminary version of the scale was applied to 1,255 patients. Using the AFC, factor loadings ranged from 0.66 to 0.90 and R2 from 0.44 to 0.81. Both the primary indicators and the model adequacy indices presented satisfactory and consistent levels. According to the NA, the items were appropriately associated with their peers, respecting the established dimensions, thus demonstrating sustainability and stability of the proposed model. CONCLUSIONS: The evidence of validity presented by EVFAM-BR indicates, for the first time in Brazil, a concise instrument that is able to assertively measure family vulnerability, potentially supporting population-based management.

Cryptic circulation of chikungunya virus in São Jose do Rio Preto, Brazil, 2015-2019.

BACKGROUND: Chikungunya virus (CHIKV) has spread across Brazil with varying incidence rates depending on the affected areas. Due to cocirculation of arboviruses and overlapping disease symptoms, CHIKV infection may be underdiagnosed. To understand the lack of CHIKV epidemics in São José do Rio Preto (SJdRP), São Paulo (SP), Brazil, we evaluated viral circulation by investigating anti-CHIKV IgG seroconversion in a prospective study of asymptomatic individuals and detecting anti-CHIKV IgM in individuals suspected of dengue infection, as well as CHIKV presence in Aedes mosquitoes. The opportunity to assess two different groups (symptomatic and asymptomatic) exposed at the same geographic region aimed to broaden the possibility of identifying the viral circulation, which had been previously considered absent. METHODOLOGY/PRINCIPAL FINDINGS: Based on a prospective population study model and demographic characteristics (sex and age), we analyzed the anti-CHIKV IgG seroconversion rate in 341 subjects by ELISA over four years. The seroprevalence increased from 0.35% in the first year to 2.3% after 3 years of follow-up. Additionally, we investigated 497 samples from a blood panel collected from dengue-suspected individuals during the 2019 dengue outbreak in SJdRP. In total, 4.4% were positive for anti-CHIKV IgM, and 8.6% were positive for IgG. To exclude alphavirus cross-reactivity, we evaluated the presence of anti-Mayaro virus (MAYV) IgG by ELISA, and the positivity rate was 0.3% in the population study and 0.8% in the blood panel samples. In CHIKV and MAYV plaque reduction neutralization tests (PRNTs), the positivity rate for CHIKV-neutralizing antibodies in these ELISA-positive samples was 46.7%, while no MAYV-neutralizing antibodies were detected. Genomic sequencing and phylogenetic analysis revealed CHIKV genotype ECSA in São José do Rio Preto, SP. Finally, mosquitoes collected to complement human surveillance revealed CHIKV positivity of 2.76% of A. aegypti and 9.09% of A. albopictus (although it was far less abundant than A. aegypti) by RT-qPCR. CONCLUSIONS/SIGNIFICANCE: Our data suggest cryptic CHIKV circulation in SJdRP detected by continual active surveillance. These low levels, but increasing, of viral circulation highlight the possibility of CHIKV outbreaks, as there is a large naïve population. Improved knowledge of the epidemiological situation might aid in outbreaks prevention.