Amazon Wildfires and Respiratory Health: Impacts during the Forest Fire Season from 2009 to 2019.

The Brazilian Amazon, a vital tropical region, faces escalating threats from human activities, agriculture, and climate change. This study aims to assess the relationship between forest fire occurrences, meteorological factors, and hospitalizations due to respiratory diseases in the Legal Amazon region from 2009 to 2019. Employing simultaneous equation models with official data, we examined the association between deforestation-induced fires and respiratory health issues. Over the studied period, the Legal Amazon region recorded a staggering 1,438,322 wildfires, with 1,218,606 (85%) occurring during August-December, known as the forest fire season. During the forest fire season, a substantial portion (566,707) of the total 1,532,228 hospital admissions for respiratory diseases were recorded in individuals aged 0-14 years and 60 years and above. A model consisting of two sets of simultaneous equations was constructed. This model illustrates the seasonal fluctuations in meteorological conditions driving human activities associated with increased forest fires. It also represents how air quality variations impact the occurrence of respiratory diseases during forest fires. This modeling approach unveiled that drier conditions, elevated temperatures, and reduced precipitation exacerbate fire incidents, impacting hospital admissions for respiratory diseases at a rate as high as 22 hospital admissions per 1000 forest fire events during the forest fire season in the Legal Amazon, 2009-2019. This research highlights the urgent need for environmental and health policies to mitigate the effects of Amazon rainforest wildfires, stressing the interplay of deforestation, climate change, and human-induced fires on respiratory health.

Novel Anti-virulence Compounds Disrupt Exotoxin Expression in MRSA.

Hemolysins are lytic exotoxins expressed in most strains of S. aureus , but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt the S. aureus transcriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, and their effects on hemolysin production in MRSA. To gain understanding into how these compounds affect hemolysis, we analyzed these exotoxins at the DNA, RNA, and protein level after in vitro treatment. While lysis of red blood cells varied between strains, DNA sequence variation did not account for it. We hypothesized that our compounds would modulate gene expression of multiple hemolysins in a laboratory strain and a clinically relevant hospital-acquired strain of MRSA, both with SCC mec type II. RNA-seq analysis of differential gene expression in untreated and compound-treated cultures revealed hundreds of differentially expressed genes, with a significant enrichment in genes involved in hemolysis. The brominated carbazole and loratadine both displayed the ability to reduce hemolysis in the laboratory strain, but displayed differential activity in a hospital-acquired strain. These results corroborate gene expression studies as well as western blots of alpha hemolysin. Together, this work suggests that small molecules may alter exotoxin production in MRSA, but that the directionality and/or magnitude of the difference is likely strain-dependent.

Nanoassembly of spider silk protein mediated by intrinsically disordered regions.

Spider silk is the self-assembling product of silk proteins each containing multiple repeating units. Each repeating unit is entirely intrinsically disordered or contains a small disordered domain. The role of the disordered domain/unit in conferring silk protein storage and self-assembly is not fully understood yet. Here, we used biophysical and biochemical techniques to investigate the self-assembly of a miniature version of a minor ampullate spidroin (denoted as miniMiSp). miniMiSp consists of two identical intrinsically disordered domains, one folded repetitive domain, and two folded terminal domains. Our data indicated that miniMiSp self-assembles into oligomers and further into liquid droplets. The oligomerization is attributed to the aggregation-prone property of both the disordered domains and the folded repetitive domain. Our results support the model of micellar structure for silk proteins at high protein concentrations. The disordered domain is indispensable for liquid droplet formation via liquid-liquid phase separation, and tyrosine residues located in the disordered domain make dominant contributions to stability of the liquid droplets. As the same tyrosine residues are also critical to fibrillation, the liquid droplets are likely an intermediate state between the solution state and the fiber state. Additionally, the terminal domains contribute to the pH- and salt-dependent self-assembly properties.

Forest cover percentage drives the peak biting time of Nyssorhynchus darlingi (Diptera: Culicidae) in the Brazilian Amazon.

BACKGROUND: Deforestation is an important driver of malaria dynamics, with a relevant impact on mosquito ecology, including larval habitat availability, blood-feeding behaviour, and peak biting time. The latter is one of several entomological metrics to evaluate vectorial capacity and effectiveness of disease control. This study aimed to test the effect of forest cover percentage on the peak biting time of Plasmodium-uninfected and infected Nyssorhynchus darlingi females. METHODS: Mosquitoes were captured utilizing human landing catch (HLC) in the peridomestic habitat in field collections carried out in the wet, wet-dry transition, and dry seasons from 2014 to 2017 in areas with active malaria transmission in Amazonian Brazil. The study locations were in rural settlements in areas with the mean annual malaria parasite incidence (Annual Parasite Incidence, API ≥ 30). All Ny. darlingi females were tested for Plasmodium spp. infection using real time PCR technique. Forest cover percentage was calculated for each collection site using QGIS v. 2.8 and was categorized in three distinct deforestation scenarios: (1) degraded, < 30% forest cover, (2) intermediate, 30-70% forest cover, and (3) preserved, > 70% forest cover. RESULTS: The highest number of uninfected female Ny. darlingi was found in degraded landscape-sites with forest cover < 30% in any peak biting time between 18:00 and 0:00. Partially degraded landscape-sites, with (30-70%) forest cover, showed the highest number of vivax-infected females, with a peak biting time of 21:00-23:00. The number of P. falciparum-infected mosquitoes was highest in preserved sites with > 70% forest cover, a peak biting at 19:00-20:00, and in sites with 30-70% forest cover at 22:00-23:00. CONCLUSIONS: Results of this study show empirically that degraded landscapes favour uninfected Ny. darlingi with a peak biting time at dusk (18:00-19:00), whereas partially degraded landscapes affect the behaviour of Plasmodium-infected Ny. darlingi by shifting its peak biting time towards hours after dark (21:00-23:00). In preserved sites, Plasmodium-infected Ny. darlingi bite around dusk (18:00-19:00) and shortly after (19:00-20:00).

Level of self-efficacy among skill-based allied health students in the University of Santo Tomas-Enriched Virtual Mode of learning: A cross-sectional study.

Background: Self-efficacy expresses a learner's perception of how well they can do in the online academic setting. Although students' academic successes can be measured by online learning self-efficacy, there is a scarcity of evidence targeted toward allied health students. Objective: The primary aim of this study is to determine the level of online self-efficacy among students from skill-based allied health programs. The secondary aim is to correlate online self-efficacy with age, sex, year level, and program of the students. Methods: This cross-sectional analytic study utilized the Online Learning Self-Efficacy Scale (OLSE) to determine students' level of self-efficacy via a survey conducted with students who underwent the Enriched Virtual Mode of learning. Descriptive statistics was used to characterize the study participants, describe the level of self-efficacy, and compare the subscales of OLSE. Inferential statistics using Spearman's rho was performed to determine the correlation. Results: A total of 117 respondents with a mean age ± SD of 20.59 ± 0.11 years old, predominantly female (71%) were included in the study. The students from allied health programs had an online self-efficacy overall mean score of 3.83 (SD=0.05; range 2.64-5.00) with the use of technology subscales weighted the highest mean score (4.24). Females have a higher average OLSE score (M=3.92, SD=0.05) compared to males. Significant correlation was found between OLSE scores to sex (r=0.260, p=0.005) and year level (r=-0.199, p=0.031) while nonsignificant correlation was found between OLSE scores to the program (r=-0.048, p=0.604) and age (r=-0.123, p=0.185). Conclusion: Students of allied health programs generally have a very good level of online self-efficacy. This study assists educators in developing proactive strategies and approaches to promote students' self-confidence across all domains and encourage them to adopt a dynamic remote learning-based approach. Educational institutions should use this opportunity to assess how well they have implemented remote learning to ensure educational continuity, especially in times of crisis.

Loratadine Combats Methicillin-Resistant Staphylococcus aureus by Modulating Virulence, Antibiotic Resistance, and Biofilm Genes.

Methicillin-resistant Staphylococcus aureus (MRSA) has evolved to become resistant to multiple classes of antibiotics. New antibiotics are costly to develop and deploy, and they have a limited effective lifespan. Antibiotic adjuvants are molecules that potentiate existing antibiotics through nontoxic mechanisms. We previously reported that loratadine, the active ingredient in Claritin, potentiates multiple cell-wall active antibiotics in vitro and disrupts biofilm formation through a hypothesized inhibition of the master regulatory kinase Stk1. Loratadine and oxacillin combined repressed the expression of key antibiotic resistance genes in the bla and mec operons. We hypothesized that additional genes involved in antibiotic resistance, biofilm formation, and other cellular pathways would be modulated when looking transcriptome-wide. To test this, we used RNA-seq to quantify transcript levels and found significant effects in gene expression, including genes controlling virulence, antibiotic resistance, metabolism, transcription (core RNA polymerase subunits and sigma factors), and translation (a plethora of genes encoding ribosomal proteins and elongation factor Tu). We further demonstrated the impacts of these transcriptional effects by investigating loratadine treatment on intracellular ATP levels, persister formation, and biofilm formation and morphology. Loratadine minimized biofilm formation in vitro and enhanced the survival of infected Caenorhabditis elegans. These pleiotropic effects and their demonstrated outcomes on MRSA virulence and survival phenotypes position loratadine as an attractive anti-infective against MRSA.

Zoonotic Malaria Risk in Serra Do Mar, Atlantic Forest, Brazil.

Here, the main goal is to assess natural infections of Plasmodium spp. in anophelines in a forest reserve from the same region where we previously found a surprisingly high rate (5.2%) of plasmodia infections (n = 25) in Kerteszia mosquitoes (N = 480) on the slopes of Serra do Mar, Atlantic Forest, Brazil. The mosquito collection sampling was carried out at the Legado das Águas Forest Reserve using CDC light traps and Shannon traps at night (5-10 pm) in 3-day collections in November 2021 and March, April, May, and November 2022. The captured specimens were morphologically identified at the species level and had their genomic DNA extracted in pools of up to 10 mosquitoes/pool. Each pool was tested using 18S qPCR and cytb nested PCR plus sequencing. A total of 5301 mosquitoes, mostly belonging to the genus Kerteszia (99.7%), were sampled and sorted into 773 pools. Eight pools positive for Plasmodium spp. were identified: four for Plasmodium spp., one for P. vivax or P. simium, one for P. malariae or P. brasilianum, and two for the P. falciparum-like parasite. After Sanger sequencing, two results were further confirmed: P. vivax or P. simium and P. malariae or P. brasilianum. The minimum infection rate for Kerteszia mosquitoes was 0.15% (eight positive pools/5285 Kerteszia mosquitoes). The study reveals a lower-than-expected natural infection rate (expected = 5.2% vs. observed = 0.15%). This low rate relates to the absence of Alouatta monkeys as the main simian malaria reservoir in the studied region. Their absence was due to a significant population decline following the reemergence of yellow fever virus outbreaks in the Atlantic Forest from 2016 to 2019. However, this also indicates the existence of alternative reservoirs to infect Kerteszia mosquitoes. The found zoonotic species of Plasmodium, including the P. falciparum-like parasite, may represent a simian malaria risk and thus a challenge for malaria elimination in Brazil.

Trichostrongylus colubriformis infection damages intestine brush board cells and could negatively impact postabsorptive parameters of Santa Ines lambs.

This study aimed to evaluate histological, digestive and postabsorptive physiological parameters in Santa Ines lambs infected with Trichostrongylus colubriformis and fed different levels of phosphorus. Therefore, eighteen Santa Ines, castrated male, six-month old, healthy lambs (initial body weight 22.4 ± 2.7 kg) were distributed in one of four treatments arranged in a 2 × 2 split-plot arrangement: Sufficient dietary P level and uninfected (SPui; n = 4), Sufficient dietary P level and infected (SPi; n = 5), Deficient dietary P level and uninfected (DPui; n = 4), Deficient dietary P level and infected (DPi; n = 5). Infected lambs received, orally, a single pulse dose of 40.000 T. colubriformis infective larval stage (L3). Animals were fed Tifton 85 hay (Cynodon ssp.; 60%), and cassava meal and maize gluten meal (40%). Measurement of nutrient apparent digestibility and nitrogen metabolism were performed in individual metabolic stalls. To achieve the trial results, it was measured methane emissions in respiratory chambers, urine purine derivatives, ruminal short-chain fatty acids (SCFA), histological cuts of duodenal mucosal tissues and passage rates fluxes, analyzed by external (Yb, Cr, and Co) and internal (iNDF) markers. Statistical procedures were performed in R studio. The fixed main effects of treatment and the interactions were tested by ANOVA, and means compared by Duncan's test at 5% significance. Apparent digestibility was not affected by treatments, however, nitrogen retained decreased (P < 0.01) and urinary nitrogen losses increased (P < 0.01) in infected animals. Small intestine digesta content, empty segment weight, and length were higher in infected animals (P < 0.05). Passage rate was not majorly affected by infection or dietary P levels. Methane emissions, SCFA concentrations, and purine derivative excretion were also not affected by treatments. Regarding the histology, the vilosity weight (P < 0.05), and crypt depth (P < 0.01) decreased in infected animals. In conclusion, T. colubriformis infection can damage intestinal mucosa and affect nitrogen metabolism, but did not affect the digesta transit, and nutrient digestibility. The P dietary levels did not promote any modification in GIT physiological parameters tested in this study.

Global Distribution of Aedes aegypti and Aedes albopictus in a Climate Change Scenario of Regional Rivalry.

Arboviral mosquito vectors are key targets for the surveillance and control of vector-borne diseases worldwide. In recent years, changes to the global distributions of these species have been a major research focus, aimed at predicting outbreaks of arboviral diseases. In this study, we analyzed a global scenario of climate change under regional rivalry to predict changes to these species' distributions over the next century. Using occurrence data from VectorMap and environmental variables (temperature and precipitation) from WorldClim v. 2.1, we first built fundamental niche models for both species with the boosted regression tree modelling approach. A scenario of climate change on their fundamental niche was then analyzed. The shared socioeconomic pathway scenario 3 (regional rivalry) and the global climate model Geophysical Fluid Dynamics Laboratory Earth System Model v. 4.1 (GFDL-ESM4.1; gfdl.noaa.gov) were utilized for all analyses, in the following time periods: 2021-2040, 2041-2060, 2061-2080, and 2081-2100. Outcomes from these analyses showed that future climate change will affect Ae. aegypti and Ae. albopictus distributions in different ways across the globe. The Northern Hemisphere will have extended Ae. aegypti and Ae. albopictus distributions in future climate change scenarios, whereas the Southern Hemisphere will have the opposite outcomes. Europe will become more suitable for both species and their related vector-borne diseases. Loss of suitability in the Brazilian Amazon region further indicated that this tropical rainforest biome will have lower levels of precipitation to support these species in the future. Our models provide possible future scenarios to help identify locations for resource allocation and surveillance efforts before a significant threat to human health emerges.

The bibliometric landscape of infectious disease research in Panama (1990-2019).

Background: This work aims to analyze the landscape of scientific publications on subjects related to One Health and infectious diseases in Panama. The research questions are: How does the One Health research landscape look like in Panama? Are historical research efforts aligned with the One Health concept? What infectious diseases have received more attention from the local scientific community since 1990? Methods: Boolean searches on the Web of Science, SCOPUS and PubMed were undertaken to evaluate the main trends of publications related to One Health and infectious disease research in the country of Panama, between 1990 and 2019. Results: 4546 publications were identified since 1990, including 3564 peer-reviewed articles interconnected with One Health related descriptors, and 211 articles focused particularly on infectious diseases. A pattern of exponential growth in the number of publications with various contributions from Panamanian institutions was observed. The rate of multidisciplinary research was moderate, whereas those of interinstitutional and intersectoral research ranged from low to very low. Research efforts have centered largely on protozoan, neglected and arthropod-borne diseases with a strong emphasis on malaria, Chagas and leishmaniasis. Conclusion: Panama has scientific capabilities on One Health to tackle future infectious disease threats, but the official collaboration schemes and strategic investment to develop further competencies need to be conciliated with modern times, aka the pandemics era. The main proposition here, addressed to the government of Panama, is to launch a One Health regional center to promote multidisciplinary, interinstitutional and intersectoral research activities in Panama and beyond.

Microcephaly and Associated Risk Factors in Newborns: A Systematic Review and Meta-Analysis Study.

Congenital microcephaly is caused by a multitude of drivers affecting maternal−fetal health during pregnancy. It is a rare outcome in high-income industrial countries where microcephaly rates are in the range of 0.3−0.9 per 1000 newborns. Prevalence of microcephaly varies considerably across developing countries and can go as high as 58 cases per 1000 live births in pregnancies exposed to infection by Zika virus (ZIKV). Not only ZIKV-infected pregnancies, but other drivers can modulate the occurrence and severity of this outcome. Here, we sought to test the ZIKV−microcephaly association vs. competing hypotheses using a meta-analysis with 8341 microcephaly cases pooled from 10,250,994 newborns in the Americas, Africa, and Asia. Analysis of risk ratios (RR) showed teratogens the most likely microcephaly-associated risk factor (RR = 3.43; 95%-CI 2.69−4.38; p-value < 0.0001), while the statistical significance of the ZIKV−microcephaly association was marginal (RR = 2.12; 95%-CI 1.01−4.48; p-value = 0.048). Other congenital infections showed strong but variable associations with microcephaly (RR = 15.24; 95%-CI 1.74−133.70; p-value = 0.014). Microcephaly cases were associated with impoverished socioeconomic settings, but this association was statistically non-significant (RR = 2.75; 95%-CI 0.55−13.78; p-value = 0.22). The marginal ZIKV−microcephaly association and statistical significance of the competing hypotheses suggest maternal ZIKV infection might not be a cause of microcephaly alone.

Lobomycosis Epidemiology and Management: The Quest for a Cure for the Most Neglected of Neglected Tropical Diseases.

Lobomycosis is a chronic disease caused by Lacazia loboi, which is endemic to the Amazon rainforest, where it affects forest dwellers in Brazil. There is no disease control program and no official therapeutic protocol. This situation contributes to an unknown disease prevalence and unmet needs of people disabled by this disease who seek access to treatment. This review provides an update on the subject with an emphasis on therapeutic advances in humans. All relevant studies that addressed epidemiology, diagnosis, or therapeutics of lobomycosis were considered. Seventy-one articles published between 1931 and 2021 were included for a narrative literature review on the epidemiology and quest for a cure. An effective therapy for lobomycosis has been found following decades of research led by the State Dermatology Program of Acre in the Amazon rainforest, where the largest number of cases occur. This discovery opened new avenues for future studies. The main recommendations here, addressed to the Brazilian Ministry of Health, are for lobomycosis to become a reportable disease to ensure that disease prevalence is measured, and that it be prioritized such that affected individuals may access treatment free-of-charge.

Reemergence of Yellow Fever in Brazil: The Role of Distinct Landscape Fragmentation Thresholds.

Yellow Fever Virus (YFV) reemergence in Brazil was followed by human suffering and the loss of biodiversity of neotropical simians on the Atlantic coast. The underlying mechanisms were investigated with special focus on distinct landscape fragmentation thresholds in the affected municipalities. An ecological study in epidemiology is employed to assess the statistical relationship between events of YFV and forest fragmentation in municipal landscapes. Negative binomial regression model showed that highly fragmented forest cover was associated with an 85% increase of events of YFV in humans and simians (RR = 1.85, CI 95% = 1.24-2.75, p=0.003) adjusted by vaccine coverage, population size, and municipality area. Intermediate levels of forest cover combined with higher levels of forest edge densities contribute to the YFV dispersion and the exponential growth of YF cases. Strategies for forest conservation are necessary for the control and prevention of YF and other zoonotic diseases that can spillover from the fragmented forest remains to populated cities of the Brazilian Atlantic coast.

Vector role and human biting activity of Anophelinae mosquitoes in different landscapes in the Brazilian Amazon.

BACKGROUND: Environmental disturbance, deforestation and socioeconomic factors all affect malaria incidence in tropical and subtropical endemic areas. Deforestation is the major driver of habitat loss and fragmentation, which frequently leads to shifts in the composition, abundance and spatial distribution of vector species. The goals of the present study were to: (i) identify anophelines found naturally infected with Plasmodium; (ii) measure the effects of landscape on the number of Nyssorhynchus darlingi, presence of Plasmodium-infected Anophelinae, human biting rate (HBR) and malaria cases; and (iii) determine the frequency and peak biting time of Plasmodium-infected mosquitoes and Ny. darlingi. METHODS: Anopheline mosquitoes were collected in peridomestic and forest edge habitats in seven municipalities in four Amazon Brazilian states. Females were identified to species and tested for Plasmodium by real-time PCR. Negative binomial regression was used to measure any association between deforestation and number of Ny. darlingi, number of Plasmodium-infected Anophelinae, HBR and malaria. Peak biting time of Ny. darlingi and Plasmodium-infected Anophelinae were determined in the 12-h collections. Binomial logistic regression measured the association between presence of Plasmodium-infected Anophelinae and landscape metrics and malaria cases. RESULTS: Ninety-one females of Ny. darlingi, Ny. rangeli, Ny. benarrochi B and Ny. konderi B were found to be infected with Plasmodium. Analysis showed that the number of malaria cases and the number of Plasmodium-infected Anophelinae were more prevalent in sites with higher edge density and intermediate forest cover (30-70%). The distance of the drainage network to a dwelling was inversely correlated to malaria risk. The peak biting time of Plasmodium-infected Anophelinae was 00:00-03:00 h. The presence of Plasmodium-infected mosquitoes was higher in landscapes with > 13 malaria cases. CONCLUSIONS: Nyssorhynchus darlingi, Ny. rangeli, Ny. benarrochi B and Ny. konderi B can be involved in malaria transmission in rural settlements. The highest fraction of Plasmodium-infected Anophelinae was caught from midnight to 03:00 h. In some Amazonian localities, the highest exposure to infectious bites occurs when residents are sleeping, but transmission can occur throughout the night. Forest fragmentation favors increases in both malaria and the occurrence of Plasmodium-infected mosquitoes in peridomestic habitat. The use of insecticide-impregnated mosquito nets can decrease human exposure to infectious Anophelinae and malaria transmission.

Dengue-2 and Guadeloupe Mosquito Virus RNA Detected in Aedes (Stegomyia) spp. Collected in a Vehicle Impound Yard in Santo André, SP, Brazil.

In 2018-2019, we conducted mosquito collections in a municipal vehicle impound yard, which is 10 km from the Serra do Mar Environmental Protection Area in Santo André, SP, Brazil. Our aim is to study arboviruses in the impound yard, to understand the transmission of arboviruses in an urban environment in Brazil. We captured the mosquitoes using human-landing catches and processed them for arbovirus detection by conventional and quantitative RT-PCR assays. We captured two mosquito species, Aedes aegypti (73 total specimens; 18 females and 55 males) and Ae. albopictus (34 specimens; 27 females and 7 males). The minimum infection rate for DENV-2 was 11.5 per 1000 (CI95%: 1-33.9). The detection of DENV-2 RNA in an Ae. albopictus female suggests that this virus might occur in high infection rates in the sampled mosquito population and is endemic in the urban areas of Santo André. In addition, Guadeloupe mosquito virus RNA was detected in an Ae. aegypti female. To our knowledge, this was the first detection of the Guadeloupe mosquito virus in Brazil.

Malaria transmission in landscapes with varying deforestation levels and timelines in the Amazon: a longitudinal spatiotemporal study.

The relationship between deforestation and malaria is a spatiotemporal process of variation in Plasmodium incidence in human-dominated Amazonian rural environments. The present study aimed to assess the underlying mechanisms of malarial exposure risk at a fine scale in 5-km2 sites across the Brazilian Amazon, using field-collected data with a longitudinal spatiotemporally structured approach. Anopheline mosquitoes were sampled from 80 sites to investigate the Plasmodium infection rate in mosquito communities and to estimate the malaria exposure risk in rural landscapes. The remaining amount of forest cover (accumulated deforestation) and the deforestation timeline were estimated in each site to represent the main parameters of both the frontier malaria hypothesis and an alternate scenario, the deforestation-malaria hypothesis, proposed herein. The maximum frequency of pathogenic sites occurred at the intermediate forest cover level (50% of accumulated deforestation) at two temporal deforestation peaks, e.g., 10 and 35 years after the beginning of the organization of a settlement. The incidence density of infected anophelines in sites where the original forest cover decreased by more than 50% in the first 25 years of settlement development was at least twice as high as the incidence density calculated for the other sites studied (adjusted incidence density ratio = 2.25; 95% CI, 1.38-3.68; p = 0.001). The results of this study support the frontier malaria as a unifying hypothesis for explaining malaria emergence and for designing specific control interventions in the Brazilian Amazon.

Female Sexual Dysfunction After Pelvic Fracture: A Comprehensive Review of the Literature.

BACKGROUND: Female sexual dysfunction (FSD) after pelvic fracture (PFx) has garnered little attention in the urology literature. AIM: To review and summarize the current evidence regarding female PFx-related sexual function. METHODS: We performed a systematic review in accordance with PRISMA guidelines, including PubMed, EMBASE, and MEDLINE. We included only English-language manuscripts and abstracts with sufficient data for inclusion. We used the search terms "female sexual dysfunction AND pelvic fracture," "sexual dysfunction AND pelvic fracture," and "female pelvic fracture AND sexual dysfunction." A total of 177 articles were identified; 41 abstracts were reviewed; of which, 19 manuscripts were reviewed. Fifteen met inclusion criteria for analysis. OUTCOMES: The main outcome measures of this study are rates and types of female sexual dysfunction after pelvic fracture. RESULTS: FSD is prevalent after PFx, with reported rates between 25% and 62%. Three studies used the validated Female Sexual Function Index. The other 12 used non-validated questionnaires or adapted quality-of-life questionnaires with specific questions regarding FSD. The most common complaints include difficulty with intercourse, dyspareunia, orgasmic dysfunction, genitourinary pain, decreased interest in intercourse, decreased satisfaction with intercourse, and pelvic floor dysfunction. Only 1 study addressed resolution of dysfunction (30 of 98 patients [30.4%]). CLINICAL IMPLICATIONS: FSD is prevalent and an under-recognized sequela of pelvic fracture. This requires future prospective study to better characterize sexual dysfunction and identify effective treatments in trauma survivors. STRENGTH AND LIMITATIONS: To Increase awareness of FSD after pelvic trauma and the impact on the quality of life in trauma survivors. The current literature is limited by a lack of standardized assessment of FSD, limited follow-up, and minimal discussion of treatment options, in addition to the inherent bias of retrospective studies. CONCLUSIONS: FSD after traumatic PFx is not uncommon, occurs mostly in young women, and can be morbid. FSD after PFx is underreported in the urology literature. Thus, all female PFx patients should be screened for FSD by validated questionnaires. The published literature offers little knowledge as to the epidemiology, evaluation, definition, and potential treatments of FSD after PFx. Prospective studies are needed to better understand female sexual function in trauma survivors and the potential methods for prevention and rehabilitation, all within the context of a multidisciplinary approach. Walton AB, Leinwand GZ, Raheem O, et al. Female Sexual Dysfunction After Pelvic Fracture: A Comprehensive Review of the Literature. J Sex Med 2021;18:467-473.

Evaluating Deep Learning models for predicting ALK-5 inhibition.

Computational methods have been widely used in drug design. The recent developments in machine learning techniques and the ever-growing chemical and biological databases are fertile ground for discoveries in this area. In this study, we evaluated the performance of Deep Learning models in comparison to Random Forest, and Support Vector Regression for predicting the biological activity (pIC50) of ALK-5 inhibitors as candidates to treat cancer. The generalization power of the models was assessed by internal and external validation procedures. A deep neural network model obtained the best performance in this comparative study, achieving a coefficient of determination of 0.658 on the external validation set with mean square error and mean absolute error of 0.373 and 0.450, respectively. Additionally, the relevance of the chemical descriptors for the prediction of biological activity was estimated using Permutation Importance. We can conclude that the forecast model obtained by the deep neural network is suitable for the problem and can be employed to predict the biological activity of new ALK-5 inhibitors.

Hanseniasis in the municipality of Western Amazon (Acre, Brazil): are we far from the goal of the World Health Organization?

ABSTRACT Background: Hanseniasis is a public health concern in developing countries. Although a decrease in the number of new cases in Brazil has been reported, there is a prevalence above that recommended in some regions. Aims: Considering the goal of the World Health Organization (WHO) to accelerate towards a leprosy-free world from 2020, the aim of this study was to analyze the epidemiological profile and leprosy trends in the city of Cruzeiro do Sul, Acre, Brazil. Methods: This retrospective cohort study analyzed the epidemiology and trends of hanseniasis between 2005 and 2018, monitoring socioeconomic and clinical epidemiological variables obtained from the Information System of Notifiable Diseases of Hanseniasis (SINAN) database. Results: A total of 422 cases of hanseniasis (284 male, 138 female) were included. The questionnaire of six patients was incomplete. The highest number of cases (89) was recorded in 2006 (11.7/10,000 inhabitants). The borderline clinical form was most common, with 45.4% of cases. Throughout the historical series, the rate of annual percentage change in the detection of new cases and cases with grade 2 disability showed a decreasing profile, at −13.9 [95% CI: −19.1, −8.2] and −13.1 [95% CI: −21.8, −5.5], respectively. The same rates were observed in patients below 15 years of age. Limitations: This study reflects the scenario in one reference center and data were obtained retrospectively. Conclusions: The incidence of hanseniasis in this reference center is declining gradually; however, the indicators show active disease transmission and late diagnosis.