Up-regulation of TNF-alpha/NFkB/SIRT1 axis drives aggressiveness and cancer stem cells accumulation in chemoresistant oral squamous cell carcinoma.

Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.

CRISPR/Cas9-mediated genome editing of Frankliniella occidentalis, the western flower thrips, via embryonic microinjection.

The western flower thrips, Frankliniella occidentalis, poses a significant challenge in global agriculture as a notorious pest and a vector of economically significant orthotospoviruses. However, the limited availability of genetic tools for F. occidentalis hampers the advancement of functional genomics and the development of innovative pest control strategies. In this study, we present a robust methodology for generating heritable mutations in F. occidentalis using the CRISPR/Cas9 genome editing system. Two eye-colour genes, white (Fo-w) and cinnabar (Fo-cn), frequently used to assess Cas9 function in insects were identified in the F. occidentalis genome and targeted for knockout through embryonic microinjection of Cas9 complexed with Fo-w or Fo-cn specific guide RNAs. Homozygous Fo-w and Fo-cn knockout lines were established by crossing mutant females and males. The Fo-w knockout line revealed an age-dependent modification of eye-colour phenotype. Specifically, while young larvae exhibit orange-coloured eyes, the colour transitions to bright red as they age. Unexpectedly, loss of Fo-w function also altered body colour, with Fo-w mutants having a lighter coloured body than wild type, suggesting a dual role for Fo-w in thrips. In contrast, individuals from the Fo-cn knockout line consistently displayed bright red eyes throughout all life stages. Molecular analyses validated precise editing of both target genes. This study offers a powerful tool to investigate thrips gene function and paves the way for the development of genetic technologies for population suppression and/or population replacement as a means of mitigating virus transmission by this vector.

An integrative review of parent education approaches in sport: Considerations for program planning and evaluation.

In recent years, there has been an increase in the delivery and evaluation of parent education programs within youth sport. Subsequently, some recent reviews of these programs have been conducted. However, one consistent issue across many of the programs and associated review papers is the lack of an appropriate evaluation framework to guide the planning or associated reporting of the outcomes of the interventions. This has limited understanding of the overall impact of sport parenting interventions. Thus, the purposes of the current study were as follows: (a) to identify commonalities in the reporting and evaluation of parent education programs; (b) to identify gaps in the reporting and evaluation of parent education programs; (c) to draw these insights together to provide suggestions regarding how the RE-AIM could be used to enhance planning and evaluation of evidence-based programs for parent education in sport. Specifically, utilizing the RE-AIM framework to provide insights into pertinent evaluation metrics, this integrative review aimed to identify commonalities and gaps in the reporting of parent education programs. The RE-AIM framework considers the essential elements to assess the external and internal validity of interventions through five dimensions: Reach, Effectiveness, Adoption, Implementation, and Maintenance (Am J Public Health. 1999;89(9):1322-1327). Subsequently, the review aimed to provide suggestions regarding strategies to enhance the planning and evaluation of evidence-based programs for parent education in sport. Overall, the analysis demonstrated that most studies presented some pertinent evaluation information related to the RE-AIM framework, such as the number of participants and contacts made, the measures used, and the program level. However, the studies also lacked information on participant exclusion criteria, the method used to select the delivery agent (e.g., parents engaged in the program), and cost measures. Overall, the current study identified various areas where programs could be enhanced, specifically related to reporting procedural elements (e.g., program design, target population, and costs) pertaining to the implementation of parent education programs.

Clinical characteristics and outcomes of COVID-19 patients with preexisting dementia: a large multicenter propensity-matched Brazilian cohort study.

BACKGROUND: Although dementia has emerged as an important risk factor for severe SARS-CoV-2 infection, results on COVID-19-related complications and mortality are not consistent. We examined the clinical presentations and outcomes of COVID-19 in a multicentre cohort of in-hospital patients, comparing those with and without dementia. METHODS: This retrospective observational study comprises COVID-19 laboratory-confirmed patients aged ≥ 60 years admitted to 38 hospitals from 19 cities in Brazil. Data were obtained from electronic hospital records. A propensity score analysis was used to match patients with and without dementia (up to 3:1) according to age, sex, comorbidities, year, and hospital of admission. Our primary outcome was in-hospital mortality. We also assessed admission to the intensive care unit (ICU), invasive mechanical ventilation (IMV), kidney replacement therapy (KRT), sepsis, nosocomial infection, and thromboembolic events. RESULTS: Among 1,556 patients included in the study, 405 (4.5%) had a diagnosis of dementia and 1,151 were matched controls. When compared to matched controls, patients with dementia had a lower frequency of dyspnoea, cough, myalgia, headache, ageusia, and anosmia; and higher frequency of fever and delirium. They also had a lower frequency of ICU admission (32.7% vs. 47.1%, p < 0.001) and shorter ICU length of stay (7 vs. 9 days, p < 0.026), and a lower frequency of sepsis (17% vs. 24%, p = 0.005), KRT (6.4% vs. 13%, p < 0.001), and IVM (4.6% vs. 9.8%, p = 0.002). There were no differences in hospital mortality between groups. CONCLUSION: Clinical manifestations of COVID-19 differ between older inpatients with and without dementia. We observed that dementia alone could not explain the higher short-term mortality following severe COVID-19. Therefore, clinicians should consider other risk factors such as acute morbidity severity and baseline frailty when evaluating the prognosis of older adults with dementia hospitalised with COVID-19.

Spatiotemporal variability in human thermal comfort perception in open-air spaces: application to the state of Minas Gerais, Brazil.

The objective of this study was to propose bioclimatic zoning to classify human thermal comfort and discomfort in the state of Minas Gerais, Brazil; both historical and future scenarios are considered. Thus, historical series (1961 to 2017) of the effective temperature index as a function of the wind (ETW) were obtained as a function of the monthly average values of the minimum, mean, and maximum dry-bulb air temperatures (tdb,min, tdb,mean, and tdb,max, respectively), in addition to the mean relative humidity ([Formula: see text], %) and mean wind speed ([Formula: see text], m s -1). The data were obtained from 34 weather stations and subjected to trend analysis by using the nonparametric Mann-Kendall test, thus enabling the simulation of future scenarios (for 2028 and 2038). Then, to define the thermal ranges of the bioclimatic zoning, maps of ETWmin, ETWmean, and ETWmax were created from geostatistical analysis. Overall, the results show warming trends for the upcoming years in Minas Gerais municipalities. All climatic seasons showed an increase in the frequency of new classifications in the upper adjacent classes, which indicates climate warming. Therefore, when considering future scenarios for the autumn and winter seasons, attention should be given to changes in predicted thermal sensation, especially in the Central Minas Gerais, Belo Horizonte Metropolitan, South/Southwest Minas, Campo das Vertentes, and Zona da Mata.

Masticatory performance, self-perception of oral health, oral health-related quality of life and nutritional status of completely edentulous elderly patients submitted to different rehabilitation treatments: A cross-sectional study.

BACKGROUND: The impact of treatments on completely edentulous individuals on masticatory performance (MP), oral health-related quality of life (OHRQoL), nutritional status (NS) and socio-economic profile (SP) is unclear in the literature. OBJECTIVE: To compare the MP, OHRQoL, NS and SP of totally edentulous elderly users of bimaxillary complete dentures (CD) and users of lower implant-supported fixed complete dentures (IFCD). METHODS: Forty participants were allocated into groups according to rehabilitation treatment (n = 20): bimaxillary CD (G1) and lower IFCD, and upper CD (G2). The evaluation of MP used almonds by the method of sieves. Four questionnaires (Geriatric Oral Health Assessment Index-GOHAI and Oral Health Impact Profile Edent-OHIP-Edent, Brazilian Economic Classification Criteria-ABEP and Mini Nutritional Assessment-MNA) were applied to assess the OHRQoL, SP and NS of the elderly, respectively. After evaluating the statistical assumptions, the Mann-Whitney (α = .05) test was applied to compare the groups regarding MP, OHRQoL, NS and SP. Spearman's correlation (α = .05) was performed to verify the correlation between the MP, the OHRQoL and the NS of the participants. RESULTS: G2 showed better MP (p < .05) in all masticatory cycles, OHRQoL (p < .05) and NS than the G1. However, the participants' self-perception of oral health did not differ between groups (p < .05). A moderate negative correlation was found between MP and OHRQoL for 40 masticatory cycles (r2 = -0.513; p = .001). CONCLUSION: Individuals rehabilitated with IFCD had a higher average monthly family income and achieved superior behaviour in MP and OHRQoL, in addition to lower risks of malnutrition when compared to individuals using bimaxillary CD.

Oral health self-perception, maximum bite force and masticatory efficiency in patients with overdentures with different attachment systems-A crossover study.

BACKGROUND: The literature is unclear about how the different attachment systems for overdentures impact the maximum bite force, the masticatory efficiency and how this impact in the oral health self-perception in patients. OBJECTIVE: To evaluate the effect of two attachment systems (O-ring and Locator) for mandibular overdenture using single implant on quality of life, maximum bite force (BF) and masticatory efficiency (ME). METHODS: Twenty-eight completely edentulous denture wearers with a mandibular symphysis implant were randomly selected and allocated into two groups in a crossover study, considering O-ring and Locator attachment types. The quality of life and self-perception of oral health were assessed using the Oral Health Impact Profile (OHIP-Edent) and Geriatric Index of Determination of Oral Health (GOHAI) questionnaires, respectively. BF was measured using a gnathodynamometer and ME by chewing silicone cubes and almonds in different numbers of cycles. RESULTS: There was no difference between the attachment systems about self-perceived oral health and impact on quality of life (p > .05). The O-ring-type system obtained a significantly higher BF than the locator-type system (p = .04). Regardless of the food chewed, no statistically significant difference was observed with the type of attachment (p > .05). The ME was directly proportional to the masticatory cycles only for almonds (p < .01). CONCLUSIONS: Locator and O-ring inserts had a similar impact on patients' quality of life, self-perception of oral health and ME. Additionally, the O-ring system exhibited superior properties in the BF.

Early ontogeny of the freshwater fish Rhytiodus microlepis (Characiformes, Anostomidae) from the Amazon basin.

The early development of the freshwater fish Rhytiodus microlepis is characterized by the description of external morphological, meristic, and morphometric changes, as well as the growth patterns, thereby establishing a reference for the identification of its larvae and juveniles. Specimens were collected from the Amazon river channel and floodplain. Ninety-seven individuals were analysed with standard length varying between 4.31 and 79.23 mm. Rhytiodus microlepis larvae are altricial, with an elongated and fusiform body, anal opening reaching the middle region of the body, and simple nostrils becoming double and tubular during development. The pigments vary from one to two chromatophores in the dorsal region of the head in pre-flexion and flexion, but later the pigmentation pattern intensifies, transverse bands appear along the body, and a conspicuous spot appears in the basal region of the caudal fin. The total number of myomeres ranges from 49 to 50. During the transition from larval (post-flexion) to the juvenile periods, the most significant anatomical changes occur, such as the presence of all fins and increased body pigmentation. Integrated myomere count and pigmentation pattern are effective for the correct identification of the initial life stages of R. microlepis from the Amazon basin. Our results expand the knowledge about the early life history of Neotropical freshwater fish species.

Population structure and reproductive indicators of the surubim Pseudoplatystoma punctifer (Siluriformes, Pimelodidae) in the São Miguel River, Amazon basin, Brazil.

Fish is an important source of food and income for a significant portion of the Amazonian population, especially those who live along the rivers and lakes in the region. Pseudoplatystoma punctifer (Castelnau, 1855), known as surubim, is a species of Neotropical catfish widely exploited by fisheries and commercially valuable in the Guaporé River basin, Brazil. However, population dynamics are poorly known in the region. To understand the population structure and reproductive biology aspects of the surubim, monthly experimental fisheries were carried out in the São Miguel River, state of Rondônia, Brazil, between August 2020 and July 2021. The captured fish were weighed, and its gonads were removed and weighed for histological analyses (microscopic description) and classification of the maturation stages (macroscopic description). The collected gonads were fixed in 10% buffered formalin, dehydrated, cut into 4-µm-thick sections, and stained with hematoxylin and eosin. A total of 34 individuals were collected (20 females and 14 males), showing positive allometric growth and condition factor from 0.81 to 1.79 for females and males, respectively. Females were larger in size and weight than males. P. punctifer reaches its first maturation at an average length of 68.30 cm, indicating the importance of respecting the minimum capture size as an alternative to ensure the natural stocks of this fishery resource in the region. The results provide support for the establishment of public policies and actions for conservation, management, and regulation of fishing.

Ergonomics, Health, and Perceptions about Remote Domestic Workposts: Study in Areas of City of João Pessoa, Paraíba, Brazil.

Home office (HO) stands out as one of the most promising and popular forms of teleworking, especially after the COVID-19 pandemic. Therefore, many companies want to implement or maintain this working method, given its numerous advantages. However, there are adverse effects that are mainly related to physical and mental health. This article presents ergonomic analyses of HOs in neighborhoods considered heat islands. Temperature levels, extreme low-frequency non-ionizing radiation (ELF-NIR), illuminance, physical layout characteristics, and physiological parameters of teleworkers were measured. The results reveal that 92% of these professionals work 6 to 8 h daily with an ambient temperature between 25 and 30 °C, illumination levels in the range 11.20-290 Lux, and ELF-NIR > 0.4 µT. The majority of teleworkers are overweight (BMI > 24.9), and some of them have blood pressure higher than average values (129 mmHg for systolic and 84 mmHg for diastolic) in addition to a reduction in the number of red blood cells and hematocrits. Symptoms such as burning sensation, dryness, tired eyes, redness, itching, and photophobia (light sensitivity) show a 68.95% similarity. These HOs do not meet the required ergonomic and health standards.

Impact of Complete Intermittent Blood Flow Restriction in Upper Limbs Strength and Neural Function.

Purpose: We aimed to investigate the chronic effects of low-load strength training (LT) with complete intermittent blood flow restriction (IBFR) on neural adaptations and strength in biceps brachii. Methods: Nineteen volunteers were randomly assigned into two different 9-week training protocols consisting of three assessment weeks and six training weeks: (a) LT with complete IBFR (LT-IBFR; n = 10) and (b) LT without complete IBFR (LT; n = 9). Strength was evaluated by predicted 1 repetition maximum (1RM) at weeks 1, 5, and 9 and neural function by root mean square (RMS) and median frequency (MDF) at sessions 1, 7, and 12 during the first three and last three repetitions. Both groups performed three sets of Scott curl with 20% of predicted 1RM interspersed with 90s rest twice a week. Results: No changes were found in predicted 1RM throughout the training protocols nor between groups. LT-IBFR group showed lower RMS in the first set than LT for the first three repetitions and higher RMS in all sets for the last three repetitions with decreases in this value across the sets with no longitudinal changes for both groups. MDF in the first three repetitions did not differentiate between groups, however, in the last three repetitions, MDF were lower for LTIBFR group in all sets and it increased across the sets for this condition with no chronical changes for both groups in both repetitions zones. These results suggest that LT-IBFR may be ineffective for increasing Q5 strength and it did not promote chronic neural adaptations.

Dyslipidemia: A Narrative Review on Pharmacotherapy.

Dyslipidemia plays a fundamental role in the development and progression of atherosclerosis. Current guidelines for treating dyslipidemia focus on low-density lipoprotein-cholesterol (LDL-C). Despite advances in the pharmacotherapy of atherosclerosis, the most successful agents used to treat this disease-statins-remain insufficient in the primary or secondary prevention of acute myocardial infarction. Advancing therapy for hypercholesterolemia with emerging new drugs, either as monotherapy or in combination, is expected to improve cardiovascular outcomes. An emerging field in dyslipidemia pharmacotherapy is research on genetic therapies and genetic modulation. Understanding the genetic mechanisms underlying lipid alterations may lead to the development of personalized treatments that directly target the genetic causes of dyslipidemia. RNA messenger (mRNA)-based therapies are also being explored, offering the ability to modulate gene expression to normalize lipid levels. Furthermore, nanotechnology raises new possibilities in drug delivery for treating dyslipidemia. Controlled-release systems, nanoparticles, and liposomes can enhance the effectiveness and safety of medications by providing more precise and sustained release. This narrative review summarizes current and emerging therapies for the management of patients with dyslipidemia.

New variants of ALMS1 gene and familial Alström syndrome case series.

OBJECTIVES: To report two new variants of ALMS1 gene and to discuss the audiological evolution and clinical phenotype in two pairs of siblings with Alström syndrome. REPORT: This paper is a multi-disciplinary diagnostic evaluation, with genetic and audiological analysis that aims to report two new variants of the ALMS1 gene and to discuss the audiological evolution and clinical phenotype in a case series of patients with familial Alström syndrome. Therefore, we describe 4 cases presenting a complete audiometric profile of two pairs of unrelated siblings, to provide a better understanding of this very rare disease. Additionally, the present study identified two heterozygous mutations in the ALMS1 gene. CONCLUSION: This Clinical Capsule Report highlights the importance of audiological monitoring throughout the development of patients with Alström syndrome. The two variants found were not previously reported in the literature, which expands the spectrum of ALMS1 variants in Alström syndrome.

Cochlear Implants after Meningitis and Otosclerosis: A Comparison between Cochlear Ossification and Speech Perception Tests.

(1) Background: Performance after Cochlear Implantation (CI) can vary depending on numerous factors. This study aims to investigate how meningitis or otosclerosis can influence CI performance. (2) Methods: Retrospective analysis of CI performance in patients with etiological diagnosis of meningitis or otosclerosis, comparing the etiologies and analyzing the image findings, along with electrode array insertion status and technique. (3) Results: Speech recognition in CI patients with otosclerosis improves faster than in patients with meningitis. Other features such as radiological findings, degree of cochlear ossification, surgical technique used and total or partial insertion of electrodes do not seem to be directly related to speech recognition test performance. (4) Conclusions: Patients should be warned that their postoperative results have a strong correlation with the disease that caused their hearing loss and that, in cases of meningitis, a longer duration of speech-language training may be necessary to reach satisfactory results.

Combined Endoscopic Cyclophotocoagulation and Phacoemulsification Versus Phacoemulsification Alone in the Glaucoma Treatment: A Systematic Review and Meta-Analysis.

The complete safety and efficacy of endoscopic cyclophotocoagulation (ECP) remain unclear in the literature and, to our knowledge, there are no current meta-analyses on phaco-ECP versus phacoemulsification alone to date. Thus, we conducted a systematic review and meta-analysis comparing these two strategies through studies, assessing the effectiveness and safety of outcomes in a population with glaucoma. The protocol for this systematic review was registered in the PROSPERO International Prospective Register of Systematic Reviews (CRD42023482376). We systematically searched PubMed, Embase, and Web of Science from inception to December 2023. A random-effects model was used for all analyses due to heterogeneity. Review Manager 5.3 (Cochrane Centre, The Cochrane Collaboration, Denmark) was used for statistical analysis. Finally, nine studies were included in this comprehensive review and a total of 5389 eyes were analyzed in our study. In comparison to the ECP and phacoemulsification group, those receiving phacoemulsification alone showed better results in best-corrected visual acuity (MD 0.09; CI 95% 0.03 to 0.16; I²=0%), but worse outcomes in intraocular pressure (IOP) (MD -1.49; 95% CI -2.29 to -0.68; I²=29%) and use medications (MD -0.75; 95% CI -0.94 to -0.56; I²=0%) in the last visit. Complication rates, both general and serious, were significantly different between the groups, indicating the potential impact of combined procedures on patient outcomes. Thus, combining ECP with phacoemulsification for glaucoma treatment showed sustained IOP reduction and decreased medication dependence. However, higher complication rates suggest careful consideration of risks. More extensive research with larger trials and longer follow-ups is needed to validate findings and address limitations, providing valuable insights into this treatment approach.

Factors associated with clinical severity in chronic venous disease: The role of functional parameters.

INTRODUCTION: Chronic venous disease (CVD) is a highly prevalent disease that presents a wide spectrum of clinical expressions due to abnormalities in the venous system. Patients often have major functional changes that can limit daily activities. However, the functional factors associated with the severity of the disease remain poorly understood. OBJECTIVE: To identify the functional factors associated with CVD severity. METHODS: Seventy-five patients with CVD (92.0% females, 49.6 ± 13.3 years) were evaluated through clinical examination, lower limb perimetry, ankle range of motion (AROM), and lower limb muscle strength by the Heel Rise test, and Sit-to-stand test. Patients were stratified according to the disease severity as mild (telangiectasia, varicose veins, or edema in the lower limbs) or severe CVD (trophic changes or venous ulcer). RESULTS: Patients with severe CVD (n = 13) were older (p = 0.002), predominantly male (p = 0.007), with reduced AROM in dorsiflexion (p = 0.028) and inversion (p = 0.009), reduced lower limb strength by the Heel Rise test (p = 0.040), and greater circumference of the calf (p = 0.020), ankle (p = 0.003), and plantar arch (p = 0.041) when compared to mild CVD (n = 62). Advanced age, male sex, lower ankle range of motion in dorsiflexion, and greater ankle and plantar arch circumferences were associated with CVD severity. However, the ankle circumference (OR 1.258, 95% CI: 1.008-1.570; p = 0.042), together with advanced age and male sex, was the only functional variable that remained independently associated with CVD severity. CONCLUSION: The increased ankle circumference was a determinant of the CVD severity and may assist in risk stratification and guide treatment goals in this population.

APEX2-based proximity proteomic analysis identifies candidate interactors for Plasmodium falciparum knob-associated histidine-rich protein in infected erythrocytes.

The interaction of Plasmodium falciparum-infected red blood cells (iRBCs) with the vascular endothelium plays a crucial role in malaria pathology and disease. KAHRP is an exported P. falciparum protein involved in iRBC remodelling, which is essential for the formation of protrusions or "knobs" on the iRBC surface. These knobs and the proteins that are concentrated within them allow the parasites to escape the immune response and host spleen clearance by mediating cytoadherence of the iRBC to the endothelial wall, but this also slows down blood circulation, leading in some cases to severe cerebral and placental complications. In this work, we have applied genetic and biochemical tools to identify proteins that interact with P. falciparum KAHRP using enhanced ascorbate peroxidase 2 (APEX2) proximity-dependent biotinylation and label-free shotgun proteomics. A total of 30 potential KAHRP-interacting candidates were identified, based on the assigned fragmented biotinylated ions. Several identified proteins have been previously reported to be part of the Maurer's clefts and knobs, where KAHRP resides. This study may contribute to a broader understanding of P. falciparum protein trafficking and knob architecture and shows for the first time the feasibility of using APEX2-proximity labelling in iRBCs.

Zinc Starvation Induces Cell Wall Remodeling and Activates the Antioxidant Defense System in Fonsecaea pedrosoi.

The survival of pathogenic fungi in the host after invasion depends on their ability to obtain nutrients, which include the transition metal zinc. This essential micronutrient is required to maintain the structure and function of various proteins and, therefore, plays a critical role in various biological processes. The host's nutritional immunity limits the availability of zinc to pathogenic fungi mainly by the action of calprotectin, a component of neutrophil extracellular traps. Here we investigated the adaptive responses of Fonsecaea pedrosoi to zinc-limiting conditions. This black fungus is the main etiological agent of chromoblastomycosis, a chronic neglected tropical disease that affects subcutaneous tissues. Following exposure to a zinc-limited environment, F. pedrosoi induces a high-affinity zinc uptake machinery, composed of zinc transporters and the zincophore Pra1. A proteomic approach was used to define proteins regulated by zinc deprivation. Cell wall remodeling, changes in neutral lipids homeostasis, and activation of the antioxidant system were the main strategies for survival in the hostile environment. Furthermore, the downregulation of enzymes required for sulfate assimilation was evident. Together, the adaptive responses allow fungal growth and development and reveals molecules that may be related to fungal persistence in the host.

Echocardiographic Detection of Regional Wall Motion Abnormalities Using Artificial Intelligence Compared to Human Readers.

BACKGROUND: Although regional wall motion abnormality (RWMA) detection is foundational to transthoracic echocardiography, current methods are prone to interobserver variability. We aimed to develop a deep learning (DL) model for RWMA assessment and compare it to expert and novice readers. METHODS: We used 15,746 transthoracic echocardiography studies-including 25,529 apical videos-which were split into training, validation, and test datasets. A convolutional neural network was trained and validated using apical 2-, 3-, and 4-chamber videos to predict the presence of RWMA in 7 regions defined by coronary perfusion territories, using the ground truth derived from clinical transthoracic echocardiography reports. Within the test cohort, DL model accuracy was compared to 6 expert and 3 novice readers using F1 score evaluation, with the ground truth of RWMA defined by expert readers. Significance between the DL model and novices was assessed using the permutation test. RESULTS: Within the test cohort, the DL model accurately identified any RWMA with an area under the curve of 0.96 (0.92-0.98). The mean F1 scores of the experts and the DL model were numerically similar for 6 of 7 regions: anterior (86 vs 84), anterolateral (80 vs 74), inferolateral (83 vs 87), inferoseptal (86 vs 86), apical (88 vs 87), inferior (79 vs 81), and any RWMA (90 vs 94), respectively, while in the anteroseptal region, the F1 score of the DL model was lower than the experts (75 vs 89). Using F1 scores, the DL model outperformed both novices 1 (P = .002) and 2 (P = .02) for the detection of any RWMA. CONCLUSIONS: Deep learning provides accurate detection of RWMA, which was comparable to experts and outperformed a majority of novices. Deep learning may improve the efficiency of RWMA assessment and serve as a teaching tool for novices.

Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings.

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication.