Expressions of inequalities in access to health services in Latin America: a scoping review. / Expressões das desigualdades no acesso aos serviços de saúde na América Latina: uma revisão de escopo.

Latin America is one of the most unequal regions in the world. Due to colonization and occupation of the territory, structural inequalities mark people's living and health conditions. In health, we can observe how different dimensions of inequalities condition access and user experience in the service. This scoping review aimed to map and analyze the expressions of inequalities in access to health services in Latin American countries from the scientific production of the last ten years, from which 272 articles were selected. The categorical analysis classified articles into five dimensions, which characterize the expressions of inequalities in access to health services: socioeconomic, geospatial, ethnic/racial, gender, and people with disabilities. The most frequent access barriers were socioeconomic or ability to pay, geographic or transportation difficulty, availability of services, cultural/ethnic, communication, and architecture. The main conditioning factors of health inequalities were income, schooling, transportation, and living conditions. Combating health inequalities requires proposing structuring and sectorial policies.

A América Latina é uma das regiões mais desiguais do mundo. Desigualdades estruturais, fruto dos processos de colonização e ocupação do território, marcam as condições de vida e saúde das pessoas. Na saúde, é possível observar como diferentes dimensões das desigualdades condicionam o acesso e a experiência do usuário no serviço. Objetivou-se mapear e analisar as expressões das desigualdades no acesso aos serviços de saúde nos países da América Latina a partir da produção científica dos últimos dez anos. O desenho de estudo foi a revisão de escopo, por meio da qual foram selecionados 272 artigos. A análise categorial permitiu a classificação dos artigos em cinco dimensões, que caracterizam as expressões das desigualdades no acesso aos serviços de saúde: socioeconômica, geoespacial, étnica/racial, gênero e de pessoas com deficiência. As barreiras de acesso mais frequentes foram: socioeconômica ou capacidade de pagamento; geográfica ou dificuldade de transporte; disponibilidade de serviços; cultural/étnica; comunicação; e arquitetônica. Os principais fatores condicionantes das desigualdades em saúde foram renda, escolaridade, transporte e condições de moradia. O enfrentamento das desigualdades em saúde requer a proposição de políticas estruturantes e setoriais.

Black Crust Complex: Influence of Temperature and Period of Wetness on the Development of Fungi in Hevea brasiliensis.

The objective of this work was to evaluate the development of Davidiella sp. and its asexual form, Cladosporium sp., under different environmental conditions in the rubber tree (Hevea brasiliensis). Rubber tree leaves were inoculated with a spore suspension and kept in a humid chamber under different temperatures and wetness periods. The behavior of the fungi was evaluated using a scanning electron microscope (SEM) and an ultraviolet light microscope (UV). In the images obtained in SEM, four hours after inoculation of the fungus, it was possible to verify the germination and penetration of conidia at temperatures of 10 to 20 °C. The formation of conidiophores was verified from six hours after inoculation, indicating that it is in the reproductive period. In the sexual phase, in SEM, from four hours after inoculation, it was possible to verify the formation of small protuberances at temperatures between 10 and 20 °C. These black dots evolve into circular, protruding black spots, like the symptoms of black crust, with apparent spore formation on them. The data obtained from the UV analyses corroborate those from SEM, showing that the fungus has good development in its two phases between temperatures of 20 and 25 °C and that the period of wetness on the leaf can contribute to the initial development of the pathogen.

Antibiofilm effect of biogenic silver nanoparticle alone and combined with polymyxin B against carbapenem-resistant Acinetobacter baumannii.

Acinetobacter baumannii is a bacteria associated with nosocomial infections and outbreaks, difficult to control due to its antibiotic resistance, ability to survive in adverse conditions, and biofilm formation adhering to biotic and abiotic surfaces. Therefore, this study aimed to evaluate the antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) and polymyxin B alone and combined in biofilms formed by isolates of carbapenem-resistant A. baumannii (CR-Ab). In the biofilm formation inhibition assay, CR-Ab strains were exposed to different concentrations of the treatments before inducing biofilm formation, to determine the ability to inhibit/prevent bacterial biofilm formation. While in the biofilm rupture assay, the bacterial biofilm formation step was previously carried out and the adhered cells were exposed to different concentrations of the treatments to evaluate their ability to destroy the bacterial biofilm formed. All CR-Ab isolates and ATCC® 19606™ used in this study are strong biofilm formers. The antibiofilm activity of Bio-AgNP and polymyxin B against CR-Ab and ATCC® 19606™ demonstrated inhibitory and biofilm-disrupting activity. When used in combination, Bio-AgNP and polymyxin B inhibited 4.9-100% of biofilm formation in the CR-Ab isolates and ATCC® 19606™. Meanwhile, when Bio-AgNP and polymyxin B were combined, disruption of 6.8-77.8% of biofilm formed was observed. Thus, antibiofilm activity against CR-Ab was demonstrated when Bio-AgNP was used alone or in combination with polymyxin B, emerging as an alternative in the control of CR-Ab strains.

Hormone replacement therapy did not alleviate temporomandibular joint inflammatory pain in ovariectomized rats.

This study had the aim of examining the relationships between variations in estrogen levels resulting from ovariectomy, and estrogen hormone replacement therapy (HRT) in rats subjected to an orofacial inflammatory pain model. Eighty adult female Wistar rats were initially divided into 2 groups: Sham or ovariectomy (OVX-D1). Seven days later (D7), the rats were subjected to an unilateral infiltration of Freund's Complete Adjuvant (CFA) or saline solution into the right temporomandibular joint (TMJ). Then, rats received 17ß-estradiol (28 µg/kg/day) or placebo for 21 days (D10-D31). Nociception was evaluated by the von Frey (VF) and the Hot Plate (HP) tests, and depressive-like behavior by the Forced Swimming (FS) test. On D32 all rats were euthanized and serum, hippocampus and brainstem were collected. The CFA groups presented a mechanical hyperalgesia until day 21 (p ≤ 0.05). No differences were observed among groups in the HP (p = 0.735), and in the immobility and swimming time of the FS (p = 0.800; p = 0.998, respectively). In the brainstem, there was a significant difference in the TNF-ɑ levels (p = 0.043), and a marginal significant difference in BDNF levels (p = 0.054), without differences among groups in the hippocampal BDNF and TNF-ɑ levels (p = 0.232; p = 0.081, respectively). In conclusion, the hormone replacement therapy did not alleviate orofacial pain in ovariectomized rats. However, there is a decrease in brainstem TNF-ɑ levels in the animals submitted to both models, which was partially reverted by HRT.

Simplified fish larval supply in coastal areas after a dam burst in Brazil.

Coastal and estuarine systems play an important role in the maintenance of marine biodiversity, providing nursery, feeding, developmental and reproductive areas for terrestrial and aquatic species. The Fundão dam collapse is considered one of the biggest environmental disasters in Brazil, causing great social, economic and ecological damage in the affected areas. In our study, we used beta diversity and its components as a tool to monitor the spatio-temporal variation of fish larvae in four marine areas adjacent to the Doce River. The results show that the four areas undergo different spatio-temporal dynamics, with the composition of fish larvae in the Doce being simplified in the last years after the dam burst, compared to the other adjacent marine areas. In addition, turbidity is an important factor that has caused the homogenization of the larval composition of the Doce, demonstrating that mud resuspension events can cause a decrease in diversity and also suggesting the toxicity of the mud composition. The change from negative to positive additive and colonizing components in recent years suggests a slight recovery of diversity in the Doce compared to other marine areas. Finally, we have shown that some species may be tolerant to the impact, but with probable behavioral, energetic and physiological costs, which justifies the constant monitoring of these areas.

Inverted amino acids reduce the adhesion and biofilm biomass of early oral colonizers.

BACKGROUND: Early colonizers adhere to the dental surface and facilitate the initial adhesion of secondary colonizers to form oral biofilms, which may cause oral infections. OBJECTIVES: This study aimed to determine the antimicrobial, anti-adhesion and antibiofilm potency of inverted amino acids on early colonizer streptococci and their mixed species. MATERIAL AND METHODS: The following test strains were used: Streptococcus gordonii (American Type Culture Collection (ATCC) 35105); Streptococcus mitis (ATCC 49456); Streptococcus oralis (ATCC 10557); Streptococcus salivarius (ATCC 7073); and Streptococcus sanguinis (ATCC BAA-1455). The concentration-dependent antimicrobial potency of d-alanine (d-ala), d-arginine (d-arg), d-leucine (d-leu), d-methionine (d-met), and d-tryptophan (d-try) was determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method with AlamarBlue modification. The adhesion of primary colonizers in the presence of 25-mM d-amino acids (dAAs) was assessed using the colony forming unit (CFU) assay. The CFU assay was conducted on 24-h flow cell bacterial biofilm models after exposure to 25-mM inverted dAAs. RESULTS: No minimum inhibitory concentration (MIC) point was detected at any concentration tested. The minimum bactericidal concentration (MBC) point was not observed. The adhesion of S. mitis, S. oralis and mixed species was reduced by all tested dAAs. No adverse effects were observed on S. gordonii with any of the tested dAAs. The biofilm biomass of test strains under flow conditions was significantly reduced after a 5-min exposure to all tested dAAs at 25-mM concentration. CONCLUSIONS: D-amino acids did not inhibit bacterial growth and did not show bactericidal or bacteriostatic effects on test strains at any concentration tested (ranging from 6.25 mM to 100 mM). However, dAAs effectively inhibit the adhesion of early colonizers, thereby preventing the formation of oral biofilm.

Synthetic antimicrobial peptides: activity against vancomycin-resistant Enterococcus faecalis and modulation of chloramphenicol antibacterial activity.

AIMS: Enterococcus faecalis (E. faecalis) is a leading cause of nosocomial infection and presents a wide spectrum of antibiotic resistance, being vancomycin-resistant Enterococcus (VRE) one of the most relevant. Synthetic antimicrobial peptides (SAMPs) are currently a promising option to overcome antimicrobial resistance. Thus, the purpose of this study was to assess the effect of eight SAMPs against vancomycin-resistant E. faecalis, as well as to investigate their mechanism of action and synergy with conventional antibiotics. METHODS AND RESULTS: Here, eight SAMPs, Mo-CBP3-PepI, Mo-CBP3-PepII, Mo-CBP3-PepIII, RcAlb-PepI, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA, were tested for antibacterial activity in vitro against E. faecalis (ATCC® 51299) through broth microdilution. A maximum of 48% of E. faecalis growth inhibition was achieved by treatment with SAMPs alone. However, when these peptides were combined with the antibiotic chloramphenicol, assessed by checkerboard method, the inhibition increased to 55%-76% of inhibition, two to three-folds of increase if compared to the effects of the compounds alone. Microscopic analysis showed that E. faecalis cells treated with a combination of SAMPs and chloramphenicol resulted in bacterial membrane damage. The biofilm inhibition maximum was 22% for SAMPs alone, when combined with chloramphenicol, the maximum increased to 33%. CONCLUSIONS: SAMPs and their combination with chloramphenicol demonstrate antibacterial activity against E. faecalis, possibly by inducing bacterial membrane damage.

An adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in familial hypercholesterolemia: A pilot study protocol

BACKGROUND AND AIMS: A healthy diet is one of the pillars of familial hypercholesterolemia (FH) treatment. However, the best dietary pattern and indication for specific supplementation have not been established. Our aim is to conduct a pilot study to assess the effect of an adapted cardioprotective diet with or without phytosterol and/or krill oil supplement in participants with a probable or definitive diagnosis of FH, treated with moderate/high potency statins. METHODS: A national, multicenter, factorial, and parallel placebocontrolled randomized clinical trial with a superiority design and 1:1:1:1 allocation rate will be conducted. The participants will undergo whole exome sequencing and be allocated into four treatment groups: 1) a cardioprotective diet adapted for FH (DICAFH) þ phytosterol placebo þ krill oil placebo; 2) DICA-FH þ phytosterol 2 g/day þ krill oil placebo; 3) DICA-FH þ phytosterol placebo þ krill oil 2 g/day; or 4) DICA-FH þ phytosterol 2 g/day þ krill oil 2 g/day. The primary outcomes will be low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) levels and adherence to treatment after a 120-day follow-up. LDL- and high-density lipoprotein (HDL)-cholesterol subclasses, untargeted lipidomics analysis, adverse events, and protocol implementation components will also be assessed. RESULTS: A total of 58 participants were enrolled between May e August 2023. After the end of the follow-up period, the efficacy and feasibility results of this pilot study will form the basis of the design of a large-scale randomized clinical trial. CONCLUSIONS: This study's overall goal is to recommend dietary treatment strategies in the context of FH.

Effects from medications on functional biomarkers of aging in three longitudinal studies of aging in Sweden.

Antihypertensive, lipid-lowering, and blood glucose-lowering drugs have slowed down the aging process in animal models. In humans, studies are limited, have short follow-up times, and show mixed results. Therefore, this study aimed to estimate the effects of commonly used medications on functional aging, cognitive function, and frailty. We included information on individuals from three Swedish longitudinal population-based studies collected between 1986 and 2014. Our exposures were the 21 most used groups of medications among individuals aged 65 years and older in the Swedish population in 2022. Functional aging index (n = 1191), cognitive function (n = 1094), and frailty index (n = 1361) were the outcomes of interest. To estimate the medication effects, we used a self-controlled analysis, where each individual is his/her own control, thereby adjusting for all time-stable confounders. The analysis was additionally adjusted for time-varying confounders (chronological age, Charlson Comorbidity Index, smoking, body mass index, and the number of drugs). The participants were 65.5-82.8 years at the first in-person assessment. Adrenergics/inhalants (effect size = 0.089) and lipid-modifying agents/plain (effect size = 0.082) were associated with higher values of cognitive function (improvement), and selective calcium channel blockers with mainly vascular effects (effect size = -0.129) were associated with lower values of the functional aging index (improvement). No beneficial effects were found on the frailty index. Adrenergics/inhalants, lipid-modifying agents/plain, and selective calcium channel blockers with mainly vascular effects may benefit functional biomarkers of aging. More research is needed to investigate their clinical value in preventing adverse aging outcomes.

Impact of a research-action on vaccination indicators in the state of Minas Gerais, Brazil.

OBJECTIVE: Analyze the impact of the state research-action project on immunization indicators (vaccination coverage - VC, homogeneity of vaccination coverage - HVC, dropout rate - DR, and risk rating) before and after the intervention in municipalities and priority Regional Health Administrations/Regional Health Superintendencies (RHA/RHS). METHODS: The state research-action project was a before-after community clinical trial conducted in 212 municipalities belonging to eight RHA/RHS in the state of Minas Gerais, Brazil. The study sample comprised RHA/RHS with a decreasing trend for routine vaccination coverage in children under one year from 2015 to 2020. This study used secondary VC and DR data from 10 immunobiologicals recommended for children younger than two years from January to December 2021 (pre-intervention period, prior to the state research-action project) and from January to December 2022 (post-intervention period). The categorical variables were presented in proportions, and initially, a comparison was made between those of DR, HVC, and the risk rating for the transmission of vaccine-preventable diseases, according to the two periods (2021 and 2022), using the McNemar test. RESULTS: All immunization indicators increased after conducting the research-action project. In 2021, 80.66% of the state's municipalities had a risk rating for the transmission of vaccine-preventable diseases as "high and very high." In 2022, the value reduced to 68.40%. CONCLUSIONS: Risk rating for the transmission of vaccine-preventable diseases is an important mechanism to assist managers in defining priorities. The state research-action project used a method that enabled the construction and execution of unique action plans for each municipality, directing the improvement of immunization indicators in the state.

Oncopig bladder cancer cells recapitulate human bladder cancer treatment responses in vitro.

Introduction: Bladder cancer is a common neoplasia of the urinary tract that holds the highest cost of lifelong treatment per patient, highlighting the need for a continuous search for new therapies for the disease. Current bladder cancer models are either imperfect in their ability to translate results to clinical practice (mouse models), or rare and not inducible (canine models). Swine models are an attractive alternative to model the disease due to their similarities with humans on several levels. The Oncopig Cancer Model has been shown to develop tumors that closely resemble human tumors. However, urothelial carcinoma has not yet been studied in this platform. Methods: We aimed to develop novel Oncopig bladder cancer cell line (BCCL) and investigate whether these urothelial swine cells mimic human bladder cancer cell line (5637 and T24) treatment-responses to cisplatin, doxorubicin, and gemcitabine in vitro. Results: Results demonstrated consistent treatment responses between Oncopig and human cells in most concentrations tested (p>0.05). Overall, Oncopig cells were more predictive of T24 than 5637 cell therapeutic responses. Microarray analysis also demonstrated similar alterations in expression of apoptotic (GADD45B and TP53INP1) and cytoskeleton-related genes (ZMYM6 and RND1) following gemcitabine exposure between 5637 (human) and Oncopig BCCL cells, indicating apoptosis may be triggered through similar signaling pathways. Molecular docking results indicated that swine and humans had similar Dg values between the chemotherapeutics and their target proteins. Discussion: Taken together, these results suggest the Oncopig could be an attractive animal to model urothelial carcinoma due to similarities in in vitro therapeutic responses compared to human cells.

Population genomic evidence of structured and connected Plasmodium vivax populations under host selection in Latin America.

Pathogen genomic epidemiology has the potential to provide a deep understanding of population dynamics, facilitating strategic planning of interventions, monitoring their impact, and enabling timely responses, and thereby supporting control and elimination efforts of parasitic tropical diseases. Plasmodium vivax, responsible for most malaria cases outside Africa, shows high genetic diversity at the population level, driven by factors like sub-patent infections, a hidden reservoir of hypnozoites, and early transmission to mosquitoes. While Latin America has made significant progress in controlling Plasmodium falciparum, it faces challenges with residual P. vivax. To characterize genetic diversity and population structure and dynamics, we have analyzed the largest collection of P. vivax genomes to date, including 1474 high-quality genomes from 31 countries across Asia, Africa, Oceania, and America. While P. vivax shows high genetic diversity globally, Latin American isolates form a distinctive population, which is further divided into sub-populations and occasional clonal pockets. Genetic diversity within the continent was associated with the intensity of transmission. Population differentiation exists between Central America and the North Coast of South America, vs. the Amazon Basin, with significant gene flow within the Amazon Basin, but limited connectivity between the Northwest Coast and the Amazon Basin. Shared genomic regions in these parasite populations indicate adaptive evolution, particularly in genes related to DNA replication, RNA processing, invasion, and motility - crucial for the parasite's survival in diverse environments. Understanding these population-level adaptations is crucial for effective control efforts, offering insights into potential mechanisms behind drug resistance, immune evasion, and transmission dynamics.

Senolytic treatment fails to improve ovarian reserve or fertility in female mice.

Senescent cell number increases with age in different tissues, leading to greater senescent cell load, proinflammatory stress, and tissue dysfunction. In the current study, we tested the efficacy of senolytic drugs to reduce ovarian senescence and improve fertility in reproductive age female mice. In the first experiment, 1-month-old C57BL/6 female mice were treated every other week with D + Q (n = 24) or placebo (n = 24). At 3 and 6 months of age, female mice were mated with untreated males to evaluate pregnancy rate and litter size. In the second experiment, 6-month-old C57BL/6 female mice were treated monthly with D + Q (n = 30), fisetin (n = 30), or placebo (n = 30). Females were treated once a month until 11 months of age, then they were mated with untreated males for 30 days to evaluate pregnancy rate and litter size. In the first experiment, D + Q treatment did not affect pregnancy rate (P = 0.68), litter size (P = 0.58), or ovarian reserve (P > 0.05). Lipofuscin staining was lower in females treated with D + Q (P = 0.04), but expression of senescence genes in ovaries was similar. In the second experiment, D + Q or fisetin treatment also did not affect pregnancy rate (P = 0.37), litter size (P = 0.20), or ovarian reserve (P > 0.05). Lipofuscin staining (P = 0.008) and macrophage infiltration (P = 0.002) was lower in fisetin treated females. Overall, treatment with D + Q or fisetin did not affect ovarian reserve or fertility but did decrease some senescence markers in the ovary.

Facial Analysis of Patients with Unilateral or Bilateral Cleft Lip and Palate Using 3D Stereophotogrammetry.

OBJECTIVES: To evaluate the quantitative values of linear and angular facial anthropometrics in patients with unilateral cleft lip and palate (UCLP) and compare them with those of patients with bilateral cleft lip and palate (BCLP) using three-dimensional (3D) facial imaging. DESIGN: Retrospective, observational, and cross-sectional study. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies/USP (HRAC/USP). PATIENTS/ PARTICIPANTS: In total, 61 non-syndromic patients with CLP who underwent multidisciplinary treatment and rehabilitated with a prosthesis were enrolled and divided into those with UCLP (G1; n = 31) and those with BCLP (G2; n = 30). INTERVENTION: Facial images were captured using a 3D camera after landmarks were marked on each patient's face. The software evaluated linear and angular parameters. Statistical tests were applied. Significance was determined as P < 0.05. MAIN OUTCOME MEASUREMENTS: Overall, 22 linear and 13 angular measurements were evaluated. RESULTS: The nasal length (P = 0.08), middle third of the face (P = 0.06), base nose width (P < 0.001), nasal root width (P < 0.001), nasal tip angle (P = 0.018), philtrum width (P < 0.001), lower face width (P = 0.039) and midfacial depth (P = 0.040) were significantly higher in G2; the upper cutaneous lip height was significantly higher in G1. Sexual dimorphism was observed except for linear measurements (linear distance between the labiale superius and labiale inferius landmarks, nasal root width, and upper cutaneous lip length) and angular measurements. CONCLUSIONS: G2 had a greater length and width of nose and nasal root, nasal tip angle, philtrum width, and lower face width, midfacial depth, and midface third than G1. These findings also revealed the presence of sexual dimorphism.

The synergic and addictive activity of biogenic silver nanoparticle associated with meropenem against carbapenem-resistant Acinetobacter baumannii.

AIMS: Antibiotic management of infections caused by Acinetobacter baumannii often fails due to antibiotic resistance (especially to carbapenems) and biofilm-forming strains. Thus, the objective here was to evaluate in vitro the antibacterial and antibiofilm activity of biogenic silver nanoparticle (Bio-AgNP) combined with meropenem, against multidrug-resistant isolates of A. baumannii. METHODS AND RESULTS: In this study, A. baumannii ATCC® 19606™ and four carbapenem-resistant A. baumannii (Ab) strains were used. The antibacterial activity of Bio-AgNP and meropenem was evaluated through broth microdilution. The effect of the Bio-AgNP association with meropenem was determined by the checkboard method. Also, the time-kill assay and the integrity of the bacterial cell membrane were evaluated. Furthermore, the antibiofilm activity of Bio-AgNP and meropenem alone and in combination was determined. Bio-AgNP has antibacterial activity with minimum inhibitory concentration (MIC) and minimum bactericidal concentration ranging from 0.46 to 1.87 µg ml-1. The combination of Bio-AgNP and meropenem showed a synergistic and additive effect against Ab strains, and Bio-AgNP was able to reduce the MIC of meropenem from 4- to 8-fold. Considering the time-kill of the cell, meropenem and Bio-AgNP when used in combination reduced bacterial load to undetectable levels within 10 min to 24 h after treatment. Protein leakage was observed in all treatments evaluated. When combined, meropenem/Bio-AgNP presents biofilm inhibition for Ab2 isolate and ATCC® 19606™, with 21% and 19%, and disrupts the biofilm from 22% to 50%, respectively. The increase in nonviable cells in the biofilm can be observed after treatment with Bio-AgNP and meropenem in carbapenem-resistant A. baumannii strains. CONCLUSIONS: The combination of Bio-AgNP with meropenem can be a therapeutic option in the treatment of infections caused by carbapenem-resistant A. baumannii.

Integrated analysis of RNA-seq datasets reveals novel targets and regulators of COVID-19 severity.

During the COVID-19 pandemic, RNA-seq datasets were produced to investigate the virus-host relationship. However, much of these data remains underexplored. To improve the search for molecular targets and biomarkers, we performed an integrated analysis of multiple RNA-seq datasets, expanding the cohort and including patients from different countries, encompassing severe and mild COVID-19 patients. Our analysis revealed that severe COVID-19 patients exhibit overexpression of genes coding for proteins of extracellular exosomes, endomembrane system, and neutrophil granules (e.g., S100A9, LY96, and RAB1B), which may play an essential role in the cellular response to infection. Concurrently, these patients exhibit down-regulation of genes encoding components of the T cell receptor complex and nucleolus, including TP53, IL2RB, and NCL Finally, SPI1 may emerge as a central transcriptional factor associated with the up-regulated genes, whereas TP53, MYC, and MAX were associated with the down-regulated genes during COVID-19. This study identified targets and transcriptional factors, lighting on the molecular pathophysiology of syndrome coronavirus 2 infection.

Unraveling the transcriptional features and gene expression networks of pathogenic and saprotrophic Ophiostoma species during the infection of Ulmus americana.

American elm (Ulmus americana), highly prized for its ornamental value, has suffered two successive outbreaks of Dutch elm disease (DED) caused by ascomycete fungi belonging to the genus Ophiostoma. To identify the genes linked to the pathogenicity of different species and lineages of Ophiostoma, we inoculated 2-year-old U. americana saplings with six strains representing three species of DED fungi, and one strain of the saprotroph Ophiostoma quercus. Differential expression analyses were performed following RNA sequencing of fungal transcripts recovered at 3- and 10-days post-infection. Based on a total of 8,640 Ophiostoma genes, we observed a difference in fungal gene expression depending on the strain inoculated and the time of incubation in host tissue. Some genes overexpressed in the more virulent strains of Ophiostoma encode hydrolases that possibly act synergistically. A mutant of Ophiostoma novo-ulmi in which the gene encoding the ogf1 transcription factor had been deleted did not produce transcripts for the gene encoding the hydrophobin cerato-ulmin and was less virulent. Weighted gene correlation network analyses identified several candidate pathogenicity genes distributed among 13 modules of interconnected genes.IMPORTANCEOphiostoma is a genus of cosmopolitan fungi that belongs to the family Ophiostomataceae and includes the pathogens responsible for two devastating pandemics of Dutch elm disease (DED). As the mechanisms of action of DED agents remain unclear, we carried out the first comparative transcriptomic study including representative strains of the three Ophiostoma species causing DED, along with the phylogenetically close saprotrophic species Ophiostoma quercus. Statistical analyses of the fungal transcriptomes recovered at 3 and 10 days following infection of Ulmus americana saplings highlighted several candidate genes associated with virulence and host-pathogen interactions wherein each strain showed a distinct transcriptome. The results of this research underscore the importance of investigating the transcriptional behavior of different fungal taxa to understand their pathogenicity and virulence in relation to the timeline of infection.

Virtual platelet cross-matching as transfusion management for patients with immune platelet refractoriness.

BACKGROUND AND OBJECTIVES: This study describes the use of the Epvix platform for virtual cross-matching (VC) of human leucocyte antigen (HLA)-compatible platelets for patients with immune platelet refractoriness, and demonstrates effectiveness of the selected platelets. MATERIALS AND METHODS: A prospective cohort of haematological patients was evaluated from 2018 to 2022. HLA-typed donor bank profile was previously uploaded to the Epvix platform. Each patient's antibody reactivity panel (PRA) was included in the platform. Then, search, selection and VC were performed, and 24-h-corrected count increment (CCI) platelet transfusion was calculated (reference ≥2500). RESULTS: Six patients were included (four female, two male), with mean age of 61 years. HLA antibodies were detected as the cause of immunity for all patients, whereas four patients also had non-immune causes. High percentage of alloimmunization was detected in all studied patients (mean PRA: 85.7%). Thirty different donors were able to schedule and perform platelet donations. The mean 24-h CCI count was 9882. All platelet transfusions achieved a satisfactory CCI count except for two transfusion events. Presence of non-immune causes identified in these two cases could account for the unsatisfactory CCI. CONCLUSION: Epvix is a free application hosted on the Web and uses the HLAMatchmaker algorithm to generate histocompatibility reports. This study demonstrates the efficiency of VC performed by Epvix. However, physical cross-matching will still be necessary in some instances, as the platform does not support human platelet antigen polymorphism.

Host-virus interaction between tobacco mild green mosaic virus strain U2 and tropical soda apple resulting in systemic hypersensitive necrosis and the host range, survival, spread, and molecular characterization of the virus.

BACKGROUND: Tobacco mild green mosaic virus strain U2 (TMGMV-U2) is a registered active ingredient in a bioherbicide to control tropical soda apple (TSA), Solanum viarum, an invasive weed. As required for registration, we developed empirical data on the host-virus interaction and the virus's host range, survival, spread, and genomic sequence. RESULTS: TMGMV-U2 killed TSA plants by causing systemic hypersensitive necrosis (SHN). It elicited local lesions in inoculated leaves which was followed by the plant's wilting and death. It moved from inoculated terminal leaves through the vasculature to roots and then to newly developed leaves. Phloem death was implicated in wilting and plant death. The SHN response was attenuated in plants grown at constant 32 °C. TMGMV-U2 titer in TSA was low compared to a systemically susceptible tobacco. The virus remained infective for up to 6 months in infected dead TSA tissues and in soil in which infected plants had grown. Susceptible tobacco and pepper plants grown in soil that previously had infected dead TSA or in soil amended with the virus remained asymptomatic and virus-free. A susceptible pepper crop grown in a field block following two consecutive crops of TMGMV-U2-infected susceptible tobacco grew disease-free and virus-free and without yield loss. Purified TMGMV-U2 was infective for 1 year when stored at -20 °C or 5 °C and for 1 month at room temperature. No virus spread was found in the field. Genomic analyses confirmed the registered isolate to be a U2 strain and free of satellite TMV. The TMGMV-U2-susceptible species preponderantly belonged to the Solanaceae. A few hosts that were killed belonged to this family. Several new hosts to TMGMV-U2 were found. These data enabled registration of TMGMV-U2. CONCLUSION: TMGMV-U2 can be used safely as a bioherbicide without risks to nontarget plants and the environment. © 2023 Society of Chemical Industry.

ENAM gene polymorphisms associated with dental anomalies in individuals with cleft lip and palate

Aim: This study aimed to investigate the occurrence of enamelin gene (ENAM) single nucleotide polymorphisms (SNP) and ENAM polymorphism association with dental anomalies (DA) in individuals with unilateral or bilateral cleft lip and palate (CLP). Methods: Saliva samples were collected from 147 individuals aged between 6 and 15 years-old, both genders, and divided into 4 groups: Group 1 (G1) - CLP and DA; Group 2 (G2) - CLP without DA; Group 3 (G3) - without CLP with DA; Group 4 (G4) - without CLP and DA. The genomic DNA was extracted from saliva samples and the following ENAM SNPs markers were genotyped: rs3796703, rs3796704, rs3796705, rs7671281, rs2609428, and rs35951442. Fisher exact and Pearson's Chi-square tests statistically analyzed the results (α=5%). Results: Individuals without CLP with DA (Group 3 - 19.2%) showed statistically higher prevalence of SNP rs2609428 heterozygotes (p=0.006) than individuals with CLP and DA (Group 1 - 0%). Individuals without CLP (10%) exhibited statistically higher prevalence of mutated heterozygotes/homozygous (p=0.028) than in individuals with CLP (1.3%). Conclusion: SNP rs2609428 marker of ENAM gene may be associated with dental anomalies in individuals without cleft lip and palate