RESUMEN

BACKGROUND: The LGBTQI + community encounters distinct healthcare challenges due to discrimination and inadequate understanding of their needs. Dermatologists play a crucial role in addressing this by fostering inclusiveness, recognizing individual concerns, and adopting tailored approaches, thereby promoting a more equitable healthcare system. OBJECTIVE: To address the need for an inclusive healthcare space, the authors established the first dermatological practice exclusively for transgender and non-binary patients. This article presents a comprehensive two-year experience in a public hospital. METHODS: The authors conducted a retrospective and descriptive study, analyzing the medical records of 114 patients evaluated at a specialized dermatological practice between June 2021 and May 2023. Key variables assessed included self-identified gender, age, residence, access to private healthcare, human immunodeficiency virus status, hormonal treatment, surgical interventions, consultation motives, employment stability, and family support during gender expression transition. RESULTS: The present study included 114 patients, 49.1% trans men, 39.5% trans women, and 8.8% non-binary individuals. Trans men, on average younger than trans women (p < 0.001), predominantly sought care for body modification-related concerns, particularly acne and androgenetic alopecia. In contrast, trans women exhibited a more diverse range of consultation motives typically unrelated to hormonal or surgical procedures. STUDY LIMITATIONS: This study is retrospective and limited in geographic scope. Additionally, the patient population lacked diversity in terms of Black ethnicity. CONCLUSIONS: The pioneering dermatological practice for transgender and non-binary patients exemplifies healthcare equity and cultural competence. Effective LGBTQI + healthcare requires addressing unique dermatological concerns while fostering inclusiveness and continuous learning within the medical community.

Asunto(s)

Dermatología , Personas Transgénero , Humanos , Masculino , Femenino , Estudios Retrospectivos , Adulto , Persona de Mediana Edad , Argentina , Adulto Joven , Adolescente , Derivación y Consulta , Anciano , Accesibilidad a los Servicios de Salud , Salud Pública

RESUMEN

This study aimed to describe the development of the Perceived Therapist's Knowledge about Gender Identity Diversity Scale and to preliminarily validate this scale by describing its psychometric properties. This research instrument was constructed based on the existing literature and recommendations for instrument development. Initially, a 36-item scale was devised to assess perceived openness and knowledge about gender identity diversity in therapy. The content validation process involved 12 expert judges, leading to a refined 25-item scale. Participants consisting of 57 trans and non-binary Puerto Rican individuals completed the scale. Exploratory factor analysis revealed a unidimensional structure, supporting a single factor named "perceived knowledge about gender identity diversity in therapy." The final scale demonstrated excellent reliability (α = 0.978; Sα = 0.980; ω = 0.979), indicating strong internal consistency. This validated scale contributes to assessing primarily Hispanic trans and non-binary individuals' perceptions of their therapists' knowledge about gender identity diversity.

RESUMEN

Developmental evolution and diversification of morphology can arise through changes in the regulation of gene expression or protein-coding sequence. To unravel mechanisms underlying early developmental evolution in cavefish of the species Astyanax mexicanus, we compared transcriptomes of surface-dwelling and blind cave-adapted morphs at the end of gastrulation. Twenty percent of the transcriptome was differentially expressed. Allelic expression ratios in cave X surface hybrids showed that cis-regulatory changes are the quasi-exclusive contributors to inter-morph variations in gene expression. Among a list of 108 genes with change at the cis-regulatory level, we explored the control of expression of rx3, which is a master eye gene. We discovered that cellular rx3 levels are cis-regulated in a cell-autonomous manner, whereas rx3 domain size depends on non-autonomous Wnt and Bmp signalling. These results highlight how uncoupled mechanisms and regulatory modules control developmental gene expression and shape morphological changes. Finally, a transcriptome-wide search for fixed coding mutations and differential exon use suggested that variations in coding sequence have a minor contribution. Thus, during early embryogenesis, changes in gene expression regulation are the main drivers of cavefish developmental evolution.

Asunto(s)

Characidae , Regulación del Desarrollo de la Expresión Génica , Transcriptoma , Animales , Characidae/genética , Characidae/embriología , Transcriptoma/genética , Evolución Biológica , Cuevas , Proteínas de Peces/genética , Proteínas de Peces/metabolismo , Gastrulación/genética , Evolución Molecular

RESUMEN

Trypanosoma cruzi, the etiological agent of Chagas' disease, can infect both phagocytic and non-phagocytic cells. T. cruzi gp82 and gp90 are cell surface proteins belonging to Group II trans-sialidases known to be involved in host cell binding and invasion. Phosphatidylinositol kinases (PIK) are lipid kinases that phosphorylate phospholipids in their substrates or in themselves, regulating important cellular functions such as metabolism, cell cycle and survival. Vps34, a class III PIK, regulates autophagy, trimeric G-protein signaling, and the mTOR (mammalian Target of Rapamycin) nutrient-sensing pathway. The mammalian autophagy gene Beclin1 interacts to Vps34 forming Beclin 1-Vps34 complexes involved in autophagy and protein sorting. In T. cruzi epimastigotes, (a non-infective replicative form), TcVps34 has been related to morphological and functional changes associated to vesicular trafficking, osmoregulation and receptor-mediated endocytosis. We aimed to characterize the role of TcVps34 during invasion of HeLa cells by metacyclic (MT) forms. MTs overexpressing TcVps34 showed lower invasion rates compared to controls, whilst exhibiting a significant decrease in gp82 expression in the parasite surface. In addition, we showed that T. cruzi Beclin (TcBeclin1) colocalizes with TcVps34 in epimastigotes, thus suggesting the formation of complexes that may play conserved cellular roles already described for other eukaryotes.

RESUMEN

Black soldier fly meal in pet diets is gaining acceptance. This study aimed to assess the use of black soldier fly larvae defatted meal (BSFL) and its impact on blood parameters, biochemical markers, organic antioxidant capacity, skin barrier function and skin and coat quality. A cross-over study involved eight beagle dogs with two periods of 50 days each and a washout period of seven days in between. Two approximately iso-nutritive extruded diets were evaluated, the first containing 29.5% BSFL meal and a control diet containing 26% poultry by-product meal (PBP) as protein source. Skin and coat evaluations and blood collections were conducted before and after each period. Skin barrier function was assessed by measurement of trans epidermal water loss (TEWL) and stratum corneum hydration (SCH) in belly and pinna of the dogs on days 0, 15, 30, and 45 of each period. A trend for higher antioxidant effect significant reduction in serum scavenging capacity was found with PBP for BSFL diet trough malondialdehyde and Vitamin E measurement in dog's serum 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. When fed PBP diet dogs exhibited reduction in serum cholesterol triglycerides and decreased LDL levels after 50 days, while dogs fed BSFL presented significant reduction in ALT. TEWL was significantly reduced in belly and pinna over time when dogs were fed BSFL, and TEWL in belly was significantly lower in dogs fed BSFL in comparison to PBP. while Increased SCH was also higher for the BSFL group observed in the same along the feeding period in comparison to PBP, indicating improved ability of the dogs to retain water and keep skin moisture. Improvement skin barrier function could be related to fatty acids from BSFL and increased sebaceous lipids in skin. These are responsible for to avoid water loss and improve skin protection against microbial insults. Inclusion of BSFL as protein source did not promote negative changes in blood biochemistry and had minor antioxidant effect in healthy dogs. However, it proved effective in improving skin barrier function, making BSFL a valuable alternative protein source for dogs, particularly those with sensitive skin or allergies manifesting on the skin.

Asunto(s)

Alimentación Animal , Antioxidantes , Estudios Cruzados , Dieta , Larva , Animales , Perros/fisiología , Alimentación Animal/análisis , Antioxidantes/metabolismo , Dieta/veterinaria , Larva/fisiología , Larva/química , Masculino , Femenino , Fenómenos Fisiológicos Nutricionales de los Animales , Simuliidae/fisiología , Simuliidae/química , Piel/química , Piel/metabolismo , Fenómenos Fisiológicos de la Piel

RESUMEN

Trans-resveratrol, a widely used supplement for humans, aims to enhance the body's antioxidant defense. Studies suggest that it exerts anti-inflammatory and antioxidant effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2). In order to evaluate this hypothesis, LDLr(-/-) mice were fed a Western diet to induce liver inflammation and oxidative stress. One group was fed a diet containing 0.60 mg/day of trans-resveratrol (RESV), while another group received no dietary supplementation (CONT). Oxidative stress biomarkers and inflammatory cytokines were assessed in liver homogenates. It was observed that trans-resveratrol decreased hepatic oxidative stress by increasing the GSH/GSSG ratio and reducing malondialdehyde (MDA) concentration. However, the RESV group exhibited a reduction in Nrf2 relative expression compared to CONT. Additionally, trans-resveratrol supplementation reduced nuclear factor-κB (NF-κB) expression but led to an increase in IL-6, with no significant changes observed in tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations. Overall, these findings indicate that the in vivo antioxidant impact induced by trans-resveratrol supplementation in hepatic tissue did not correlate with increase of inflammatory cytokines and Nrf2 relative expression. Further exploration of alternative mechanisms, such as direct radical scavenger activity, is warranted to elucidate the antioxidant effect.

RESUMEN

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner

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Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.

Asunto(s)

Sesquiterpenos/administración & dosificación , Enfermedades Vasculares/tratamiento farmacológico , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/lesiones , Supervivencia Celular , Lipopolisacáridos/toxicidad , Western Blotting , Óxido Nítrico Sintasa , Reacción en Cadena en Tiempo Real de la Polimerasa

RESUMEN

The inclusion of by-product coconut mesocarp skins (CMS) in diets was evaluated in feedlot lambs. The objective of this study was to evaluate CMS levels effects on carcass traits and meat quality of lambs. Thirty-five male lambs with an initial body weight of 16.9 ± 2.93 kg were distributed in a completely randomized design with five CMS levels in total dry matter (0; 4.8; 9.6; 14.4 and 19.2%) and fed during 71 d until slaughter. High levels of CMS decreased the intake of dry matter and negatively affected the performance of lambs. Fat and protein contents of Longissimus lumborum muscle (P < 0.05) and the saturated fatty acid (FA) decreased (P < 0.001) whereas polyunsaturated FA increased (P < 0.01) with the inclusion of CMS. The ratio t10/t11-18:1 increased with the inclusion of CMS (P < 0.001). The instrumental color descriptors were unaffected by CMS levels. According to the effects on the investigated meat quality traits we recommend up to 4.8% CMS in diets of confined lambs.

Asunto(s)

Alimentación Animal , Cocos , Dieta , Ácidos Grasos , Músculo Esquelético , Carne Roja , Oveja Doméstica , Animales , Masculino , Cocos/química , Alimentación Animal/análisis , Carne Roja/análisis , Dieta/veterinaria , Ácidos Grasos/análisis , Músculo Esquelético/química , Color , Composición Corporal

RESUMEN

Histidine kinases (HKs) are a central part of bacterial environmental-sensing two-component systems. They provide their hosts with the ability to respond to a wide range of physical and chemical signals. HKs are multidomain proteins consisting of at least a sensor domain, dimerization and phosphorylation domain (DHp), and a catalytic domain. They work as homodimers and the existence of two different autophosphorylation mechanisms (cis and trans) has been proposed as relevant for pathway specificity. Although several HKs have been intensively studied, a precise sequence-to-structure explanation of why and how either cis or trans phosphorylation occurs is still unavailable nor is there any evolutionary analysis on the subject. In this work, we show that AlphaFold can accurately determine whether an HK dimerizes in a cis or trans structure. By modeling multiple HKs we show that both cis- and trans-acting HKs are common in nature and the switch between mechanisms has happened multiple times in the evolutionary history of the family. We then use AlphaFold modeling to explore the molecular determinants of the phosphorylation mechanism. We conclude that it is the difference in lengths of the helices surrounding the DHp loop that determines the mechanism. We also show that very small changes in these helices can cause a mechanism switch. Despite this, previous evidence shows that for a particular HK the phosphorylation mechanism is conserved. This suggests that the phosphorylation mechanism participates in system specificity and mechanism switching provides these systems with a way to diverge.

Asunto(s)

Evolución Molecular , Histidina Quinasa , Modelos Moleculares , Fosforilación , Histidina Quinasa/metabolismo , Histidina Quinasa/química , Histidina Quinasa/genética , Proteínas Quinasas/química , Proteínas Quinasas/metabolismo , Multimerización de Proteína , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética

RESUMEN

PURPOSE: This study investigated the pharmacological effects of topical trans-anethole, a natural compound found in anise, star anise, and fennel essential oils, and its relationship with the transient receptor potential of ankyrin 1 (TRPA1). METHODS: The effects of topical anethole were assessed by eye wiping, nociceptive behaviour, and ear oedema in mice. Histological evaluations were performed on the ears of the animals topically treated with anethole. RESULTS: Anethole caused less eye irritation than capsaicin (a TRPV1 agonist) and allyl isothiocyanate (a TRPA1 agonist). Anethole (250 and 500 nmol/20 µL/paw) promoted neurogenic nociception in the paw (20.89 ± 3.53 s and 47.56 ± 8.46 s, respectively) compared with the vehicle (0.88 ± 0.38 s). HC030031 (56.1 nmol/20 µL/paw), a TRPA1 antagonist, abolished this nociceptive response. Anethole (4, 10, and 20 µmol/20 µL/ear) induced ear oedema (30.25 ± 4.78 µm, 78.00 ± 3.74 µm, and 127.50 ± 27.19 µm, respectively) compared with the vehicle (5.00 ± 0.5 µm). HC030031 (56.1 nmol/20 µL/ear) inhibited the oedema induced by anethole (10 µmol/20 µL/ear). Ears pre-treated with anethole or allyl isothiocyanate on the first day and re-exposed to these compounds on the third day showed a reduction in oedema (68.16 ± 6.04% and 38.81 ± 8.98.9%, respectively). Cross-desensitisation between anethole and allyl isothiocyanate was observed. Histological analysis confirmed the beneficial effects of anethol. CONCLUSION: As repeated topical applications of anethole induce the desensitisation of TRPA1, we suggest its clinical application as a topical formulation for treating skin diseases or managing pain associated with this receptor. Anethole may also have advantages over capsaicin and allyl isothiocyanate because of its low pungency and pleasant aroma.

Asunto(s)

Derivados de Alilbenceno , Anisoles , Canal Catiónico TRPA1 , Animales , Canal Catiónico TRPA1/antagonistas & inhibidores , Derivados de Alilbenceno/administración & dosificación , Derivados de Alilbenceno/farmacología , Ratones , Masculino , Anisoles/farmacología , Anisoles/administración & dosificación , Isotiocianatos/farmacología , Isotiocianatos/administración & dosificación , Edema/tratamiento farmacológico , Edema/inducido químicamente , Administración Tópica , Capsaicina/farmacología , Capsaicina/administración & dosificación

RESUMEN

Long noncoding RNAs (lncRNAs) are regulatory RNAs. Saccharomyces cerevisiae strains transcribe hundreds of lncRNAs. LncRNAs can regulate the expression of adjacent genes (cis-regulation) or distant genes from lncRNAs (trans-regulation). Here, we analyzed the potential global cis and trans-regulation of lncRNAs of yeast subjected to ethanol stress. For potential cis regulation, for BMA641-A and S288C strains, we observed that most lncRNA-neighbor gene pairs increased the expression at a certain point followed by a decrease, and vice versa. Based on the transcriptome profile and triple helix prediction between lncRNAs and promoters of coding genes, we observed nine different ways of potential trans regulation that work in a strain-specific manner. Our data provide an initial landscape of potential cis and trans regulation in yeast, which seems to be strain-specific.

Asunto(s)

Etanol , Regulación Fúngica de la Expresión Génica , ARN Largo no Codificante , Saccharomyces cerevisiae , Estrés Fisiológico , Saccharomyces cerevisiae/genética , ARN Largo no Codificante/genética , Etanol/farmacología , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Estrés Fisiológico/genética , Regiones Promotoras Genéticas , ARN de Hongos/genética , ARN de Hongos/metabolismo , Perfilación de la Expresión Génica/métodos , Transcriptoma

RESUMEN

As a positional and geometrical isomer of linoleic acid, trans 10, cis 12 conjugated linoleic acid (t10c12-CLA) reduces white fat by reducing food intake, modulating lipid metabolism, and stimulating energy expenditure. However, the t10c12-CLA products are mostly mixtures, making it difficult to obtain accurate results. Studies are needed to investigate the effects of pure t10c12-CLA on animals and humans. In this study, we used the biallelic transgenic (tg) mice, which could produce t10c12-CLA itself, to investigate the effects of pure t10c12-CLA on female reproductive ability. The results showed that the body and relative ovary weights had no significant difference between tg and wild-type (wt) littermates at ages 3 or 10 weeks. While the fecundity test found that tg mice had a significantly longer first litter time (32.0 ± 4.70 days vs. 21.3 ± 2.31 days, P<0.05), and a significantly lower number of litters (4.75 ± 2.75 vs. 6.67 ± 0.57, P<0.05) when compared with wt mice during continuous mating within seven months. Hormone profiles showed that serum estradiol levels did not change in tg mice; however, significantly (P<0.05) decreased progesterone and increased prostaglandin E2 levels were observed in tg mice compared with those of wt mice. Hematoxylin-eosin staining showed no pathological characteristics in tg ovaries, except for the increased atresia follicles (P<0.05). Moreover, the tg mice had a significantly more extended diestrus period than the wt mice (48.4 ± 6.38% vs. 39.6 ± 3.81%, P<0.05). In summary, t10c12-CLA could affect serum progesterone and prostaglandin E2 levels, lead to a disordered estrus cycle, and impact the reproductive performance of female mice. This study provided theoretical and biosafety recommendations for applying t10c12-CLA in female mammals.

RESUMEN

OBJECTIVE: To estimate the disability and costs of the Brazilian Unified Health System for IHD attributable to trans-fatty acid (TFA) consumption in 2019. DESIGN: This ecological study used secondary data from the Global Burden of Disease (GBD) Study 2019 to estimate the years lived with disability from IHD attributable to TFA in Brazil in 2019. Data on direct costs (purchasing power parity: 1 Int$ = R$ 2·280) were obtained from the Hospital and Ambulatory Information Systems of the Brazilian Unified Health System. Moreover, the total costs in each state were divided by the resident population in 2019 and multiplied by 10 000 inhabitants. The relationship between the socio-demographic index, disease and economic burden was investigated. SETTING: Brazil and its twenty-seven states. PARTICIPANTS: Adults aged ≥ 25 years of both sexes. RESULTS: IHD attributable to TFA consumption resulted in 11 165 years lived with disability (95 % uncertainty interval 932­18 462) in 2019 in Brazil. A total of Int$ 54 546 227 (95 % uncertainty interval 4 505 792­85 561 810) was spent in the Brazilian Unified Health System in 2019 due to IHD attributable to TFA, with the highest costs of hospitalisations, for males and individuals aged ≥ 50 years or over. The highest costs were observed in Sergipe (Int$ 6508/10 000; 95 % uncertainty interval 576­10 265), followed by the two states from the South. Overall, as the socio-demographic index increases, expenditures increase. CONCLUSIONS: TFA consumption results in a high disease and economic IHD burden in Brazil, reinforcing the need for more effective health policies, such as industrial TFA elimination, following the international agenda.

Asunto(s)

Ácidos Grasos trans , Humanos , Brasil/epidemiología , Ácidos Grasos trans/efectos adversos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Costo de Enfermedad , Personas con Discapacidad/estadística & datos numéricos , Costos de la Atención en Salud/estadística & datos numéricos , Carga Global de Enfermedades

RESUMEN

BACKGROUND: Water stress is a major danger to crop yield, hence new approaches to strengthen plant resilience must be developed. To lessen the negative effects of water stress on wheat plants, present study was arranged to investigate the role of synergistic effects of biochar, trans-zeatin riboside (t-ZR), and Azospirillum brasilense on soil improvement and enzymatic activity in water-stressed wheat. RESULTS: In a three-replication experiment comprising of four treatments (T0: Control, T1: Drought stress (DS), T2: DS + t-ZR with biochar, T3: DS + A. brasilense with biochar), we observed notable improvements in soil quality and enzymatic activities in water-stressed wheat plants with the application of t-ZR and A. brasilense with biochar. In drought stress, Treatment having the application of A. brasilense with biochar performs best as compared to the other and significant increased the enzymatic activities such as peroxidase (7.36%), catalase (8.53%), superoxide dismutase (6.01%), polyphenol oxidase (14.14%), and amylase (16.36%) in wheat plants. Different enzymatic activities showed different trends of results. Soil organic C, dissolved organic C, dissolved organic N also enhanced 29.46%, 8.59%, 22.70% respectively with the application of A. brasilense with biochar under drought stress condition. CONCLUSIONS: The synergistic action of A. brasilense and biochar creates an effective microbiological environment that supports essential plant physiological processes during drought stress. This enhancement is attributed to improved soil fertility and increased organic matter content, highlighting the potential of these novel strategies in mitigating water stress effects and enhancing crop resilience.

Asunto(s)

Azospirillum brasilense , Carbón Orgánico , Suelo , Triticum , Triticum/metabolismo , Azospirillum brasilense/fisiología , Suelo/química , Deshidratación , Sequías

RESUMEN

BACKGROUND: Currently, the effectiveness of TACE, Lenvatinib, and PD-1/L1 inhibitors used alone or in combination has been thoroughly reported. However, the differences in effectiveness between these treatment protocols require further verification. To this end, this study employs a Bayesian network meta-analysis to compare the efficacy and safety of TACE, Lenvatinib, and PD-1/L1 inhibitors, whether administered by monotherapy or in combination, providing evidence-based medicine for the treatment of unresectable HCC. PURPOSE: This study employed a network meta-analysis to evaluate the efficacy and safety of trans-arterial chemoembolization (TACE), Programmed Cell Death Protein/Ligand 1 (PD-1/L1) inhibitors, and Lenvatinib in the treatment of advanced HCC. METHODS: Literature on the treatment of advanced HCC with TACE, PD-1/L1 inhibitors, and Lenvatinib was searched for in both Chinese and English databases, including PubMed, EMBASE, ClinicalTrials.gov, Cochrane Library, CNKI, and Wanfang. Two researchers conducted independent screening and data extraction, and the meta-analysis was performed using R language with the gemtc package. RESULTS: After retrieval and screening, a total of 21 articles were included, involving 2052 participants and six treatment modalities: Lenvatinib (L), TACE (T), TACE + Lenvatinib (TL), Lenvatinib + PD-1/L1 inhibitors (LP), TACE + Lenvatinib + PD-1/L1 inhibitors (TLP), and TACE + PD-1/L1 inhibitors (TP). In terms of objective response rate (ORR), the TLP regimen provided the optimal effect. In predicting the best ORR, TLP had the highest (75.5%) probability. In terms of disease control rate (DCR), the TLP regimen showed the best effect. In predicting the best DCR, the TLP again offered the highest (76.1%) probability. In terms of overall survival (OS), the best outcome was observed in the TLP protocol. In predicting the best OS, the TLP holds the highest (86.00%) probability. Furthermore, the best outcome in progression-free survival (PFS) was found in the TLP regimen. In predicting the best PFS, the TLP still holds the highest (97.0%) result. CONCLUSION: The combination of TACE, Lenvatinib, and PD-1/L1 inhibitors appears to provide the maximum benefit for inoperable HCC patients.

Asunto(s)

Carcinoma Hepatocelular , Quimioembolización Terapéutica , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Compuestos de Fenilurea , Quinolinas , Humanos , Antineoplásicos/uso terapéutico , Antígeno B7-H1/antagonistas & inhibidores , Teorema de Bayes , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Terapia Combinada/métodos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Metaanálisis en Red , Compuestos de Fenilurea/uso terapéutico , Quinolinas/uso terapéutico , Resultado del Tratamiento

RESUMEN

Introduction: Oral transmission of T. cruzi is probably the most frequent transmission mechanism in wild animals. This observation led to the hypothesis that consuming raw or undercooked meat from animals infected with T. cruzi may be responsible for transmitting the infection. Therefore, the general objective of this study was to investigate host-pathogen interactions between the parasite and gastric mucosa and the role of meat consumption from infected animals in the oral transmission of T. cruzi. Methods: Cell infectivity assays were performed on AGS cells in the presence or absence of mucin, and the roles of pepsin and acidic pH were determined. Moreover, groups of five female Balb/c mice were fed with muscle tissue obtained from mice in the acute phase of infection by the clone H510 C8C3hvir of T. cruzi, and the infection of the fed mice was monitored by a parasitemia curve. Similarly, we assessed the infective capacity of T. cruzi trypomastigotes and amastigotes by infecting groups of five mice Balb/c females, which were infected orally using a nasogastric probe, and the infection was monitored by a parasitemia curve. Finally, different trypomastigote and amastigote inoculums were used to determine their infective capacities. Adhesion assays of T. cruzi proteins to AGS stomach cells were performed, and the adhered proteins were detected by western blotting using monoclonal or polyclonal antibodies and by LC-MS/MS and bioinformatics analysis. Results: Trypomastigote migration in the presence of mucin was reduced by approximately 30%, whereas in the presence of mucin and pepsin at pH 3.5, only a small proportion of parasites were able to migrate (∼6%). Similarly, the ability of TCTs to infect AGS cells in the presence of mucin is reduced by approximately 20%. In all cases, 60-100% of the animals were fed meat from mice infected in the acute phase or infected with trypomastigotes or amastigotes developed high parasitemia, and 80% died around day 40 post-infection. The adhesion assay showed that cruzipain is a molecule of trypomastigotes and amastigotes that binds to AGS cells. LC-MS/MS and bioinformatics analysis, also confirmed that transialidase, cysteine proteinases, and gp63 may be involved in TCTs attachment or invasion of human stomach cells because they can potentially interact with different proteins in the human stomach mucosa. In addition, several human gastric mucins have cysteine protease cleavage sites. Discussion: Then, under our experimental conditions, consuming meat from infected animals in the acute phase allows the T. cruzi infection. Similarly, trypomastigotes and amastigotes could infect mice when administered orally, whereas cysteinyl proteinases and trans-sialidase appear to be relevant molecules in this infective process.

Asunto(s)

Enfermedad de Chagas , Enfermedades Transmisibles , Trypanosoma cruzi , Femenino , Animales , Ratones , Humanos , Trypanosoma cruzi/metabolismo , Pepsina A/metabolismo , Parasitemia , Modelos Animales de Enfermedad , Cromatografía Liquida , Espectrometría de Masas en Tándem , Enfermedad de Chagas/parasitología , Mucinas

RESUMEN

Evidence has shown that consuming trans fatty acids (TFA) during development leads to their incorporation into the nervous tissue, resulting in neurological changes in flies. In this study, Drosophila melanogaster was exposed to different concentrations of hydrogenated vegetable fat (HVF) during development: substitute hydrogenated vegetable fat (SHVF), HVF 10 %, and HVF 20 %. The objective was to evaluate the effects of early trans fat exposure on cognition and associated pathways in flies. The results showed that early TFA exposure provoked a cerebral redox imbalance, as confirmed by increased reactive species (HVF 10 and 20 %) and lipid peroxidation (SHVF, HVF 10, and 20 %), reduced nuclear factor erythroid 2-related factor 2 immunoreactivity (HVF 10 and 20 %), and increased heat shock protein 70 (HVF 20 %), which was possibly responsible for decreasing superoxide dismutase (SHVF, HVF 10, and 20 %) and catalase (HVF 20 %) activities. Furthermore, the presence of TFA in nervous tissue impaired learning (HVF 10 and 20 %) and memory at 6 and 24 h (SHVF, HVF 10, and 20 %). These cognitive impairments may be linked to reduced Shank levels (HVF 20 %) and increased acetylcholinesterase activity (SHVF, HVF 10 and 20 %) observed. Our findings demonstrate that early exposure to trans fat leads to cerebral redox imbalance, altering proteins associated with stress, synaptic plasticity, and the cholinergic system, consequently leading to cognitive impairment in flies.

Asunto(s)

Disfunción Cognitiva , Ácidos Grasos trans , Animales , Drosophila melanogaster , Ácidos Grasos trans/toxicidad , Acetilcolinesterasa , Estrés Oxidativo , Disfunción Cognitiva/inducido químicamente , Plasticidad Neuronal

RESUMEN

The sesquiterpene ß-caryophyllene, classified as a phytocannabinoid compound, has been widely studied owing to its multi-target action. In addition, this compound has demonstrated application as a skin permeation promoter. In this context, this study aimed to evaluate the feasibility of associating ß-caryophyllene and indomethacin in the oily core of hydrogel thickened nanoemulsions, as well as, to evaluate the in vivo anti-inflammatory effect of this association by croton oil ear edoema induced model. After topical application, the nanoemulgels resulted in increased edoema mass when compared to the substances in their free form. Overall, the results differed from expected, and the data found may be owing to the specificities of the in vivo model applied, as well as the tested ratio between ß-caryophyllene and indomethacin (200:1). New perspectives arise from the data found regarding the evaluation of the association of terpenic compounds with indomethacin in nanoemulsified systems.

RESUMEN

OBJECTIVE: To evaluate and correlate the risk of dysphonia, the presence of vocal changes and their associated factors, and the vocal self-perception of transgender women. METHOD: Observational cross-sectional study in Brazilian transgender women. The analysis addressed their age, length of experience in the gender, perceptual-auditory and acoustic vocal aspects, scores in the General Dysphonia Risk Screening Protocol (DRSP-G), and the Voice Questionnaire for Male-to-Female Transsexuals (TVQ(MtF)). The sample was divided into two groups based on the grade of vocal deviation (Consensus Auditory-Perceptual Evaluation of Voice)-with (G.W.C.) and without vocal changes (G.N.C.)-to verify the association between the presence of vocal changes and other variables. The correlation between the grade of vocal deviation and DRSP and TVQ(MtF) scores was also verified. RESULTS: The sample included 32 transgender women with a mean age of 30.1 and 11.52 years of experience as females. Over half declared themselves Black, and a third of the sample did not have a defined profession. Use of female hormones was reported by 71.9%, the majority without a medical prescription. The mean grade of vocal deviation was 22, the dysphonia risk score was 43.47, and the TVQ(MtF) score was 59.46. Nasal and pharyngeal resonance was observed in 59.4%, and the mean fundamental frequency (f0) was 156.14 Hz. G.W.C. had a shorter experience living in the redesignated genre. The participants idealized more feminine voices than they currently had. The DRSP-G and TVQ(MtF) scores had a moderate positive correlation. CONCLUSION: The study sample had characteristics compatible with some degree of social and health vulnerability. There was a moderate impact of voice on their quality of life, and despite the high risk of dysphonia, there was a low occurrence of vocal changes. There was a correlation between the DRSP-G and TVQ(MtF) scores.

RESUMEN

Factors such as the Andean uplift, Isthmus of Panama, and climate changes have influenced bird diversity in the Neotropical region. Studying bird species that are widespread in Neotropical highlands and lowlands can help us understand the impact of these factors on taxa diversification. Our main objectives were to determine the biogeographic factors that contributed to the diversification of Euphoniinae and re-evaluate their phylogenetic relationships. The nextRAD and mitochondrial data were utilized to construct phylogenies. The ancestral distribution range was then estimated using a time-calibrated phylogeny, current species ranges, and neotropical regionalization. The phylogenies revealed two main Euphoniinae clades, Chlorophonia and Euphonia, similar to previous findings. Furthermore, each genus has distinctive subclades corresponding to morphology and geography. The biogeographic results suggest that the Andean uplift and the establishment of the western Amazon drove the vicariance of Chlorophonia and Euphonia during the Miocene. The Chlorophonia lineage originated in the Andes mountains and spread to Central America and the Mesoamerican highlands after the formation of the Isthmus of Panama. Meanwhile, the ancestral area of Euphonia was the Amazonas, from which it spread to trans-Andean areas during the Pliocene and Pleistocene due to the separation of the west lowlands from Amazonas due to the Northern Andean uplift. Chlorophonia and Euphonia species migrated to the Atlantic Forest during the Pleistocene through corridors from the East Andean Humid Forest and Amazonas. These two genera had Caribbean invasions with distinct geographic origins and ages. Finally, we suggested taxonomic changes in the genus Euphonia based on the study's phylogenetic, morphological, and biogeographic findings.