Journals
2024 EN
Lyra Raphael Rodrigues · Araujo Rodrigues Taís Helena · Costa Cristiane Maria Queiroz
+3 more
The conservation state of an environment can be a key factor in maintaining the existence of some interactions between species. The relationship between the dung beetle Dichotomius schiffleri , a habitat‐specific species endemic to the Restinga ecosystem, and endangered, and its symbiont mites can serve as a model to improve knowledge about this issue. In this study, we investigated whether the conservation state of Brazilian Restingas, a native ecosystem of the coastal zone that has suffered from anthropic pressure and impacts due to irregular occupation by humans, affects the abundance of mites present on D. schiffleri . Beetles and their associated mites were collected using pitfall traps in Conserved and Degraded Restingas at nine locations in the Brazilian states of Espírito Santo, Bahia, Sergipe, and Pernambuco. The abundance of mites associated with beetles was significantly higher in conserved sites than in degraded sites. Our findings provide evidence that Restinga degradation can affect not only abundance of dung beetle species, as previously reported, but also the ecological relationships that can be established between dung beetles and mites. The habitat quality and hosts availability are some mechanisms that may explain the maintenance of the interactions between dung beetles and mites. Finally, imbalance in ecological relationships is one more factor capable of signalling as human modified habitats impact fauna.
Journals
2024 EN
Omoto Érika Mayumi · Catelan Anderson · Santos Paulo Henrique dos
+5 more
Abstract This study aimed to evaluate the interface of universal adhesive (UA) with bulk‐fill resin (BF) and dentin, after endodontic irrigation. The pulp chamber of 96 molars was irrigated with chlorhexidine 2% (CHX) or sodium hypochlorite 5.25% (NaOCl) and restored according to three restorative protocols. Microtensile bond strength (μTBS) and nanoleakage tests were performed after 24 h of thermocycling. Kruskal Wallis, Mann–Whitney and Wilcoxon were performed ( p < 0.05). Comparing restorative systems, a difference was found only when irrigated with CHX after 24 h. CHX provided higher μTBS than NaOCl after 24 h for two restorative protocols; after thermocycling, NaOCl provided the greatest μTBS than CHX for one group. Decreased μTBS was observed for all restorative systems when CHX was used after thermocycling. NaOCl demonstrated the highest nanoleakage. The composition of UA influenced the immediate adhesion and sealing to BF when CHX was used; ageing has a deteriorating effect on adhesion and sealing for all restorative systems.
Journals
2024 EN
Moia Ana Luisa Carvalho · Branco Érika · Mesquita Ellen Yasmin Eguchi
+1 more
A local anaesthetic block performed in cranial and mandibular foramina contributes towards analgesia and the reduction of systemic anaesthesia in procedures in the oral cavity. However, anatomical differences between in wild animals may require adaptations to the anaesthetic and surgical manoeuvres of the head used in domestic animals. With that in mind, we aimed to describe the topography and morphometry of the infraorbital and mandibular foramina in Bradypus variegatus , to support perineural anaesthetic approaches in the cranio‐mandibular region of this species. We demonstrated that in B . variegatus there is no significant variability in the morphometric data, allowing access to the studied foramina to occur in a similar way in adult individuals. Finally, we understand that the techniques for the infraorbital and mandibular foramen needed to be adapted due to the anatomical singularities of the species, which culminated in new reference points for more assertive needle positioning.
Journals
2024 EN
Nakashima Akitoshi · Furuta Atsushi · YoshidaKawaguchi Mihoko
+8 more
Autophagy is a bulk degradation system that maintains cellular homeostasis by producing energy and/or recycling excess proteins. During early placentation, extravillous trophoblasts invade the decidua and uterine myometrium, facing maternal immune cells, which participate in the immune suppression of paternal and fetal antigens. Regulatory T cells will likely increase in response to a specific antigen before and during early pregnancy. Insufficient expansion of antigen‐specific Treg cells, which possess the same T cell receptor, is associated with the pathophysiology of preeclampsia, suggesting sterile systemic inflammation. Autophagy is involved in reducing inflammation through the degradation of inflammasomes and in the differentiation and function of regulatory T cells. Autophagy dysregulation induces protein aggregation in trophoblasts, resulting in placental dysfunction. In this review, we discuss the role of regulatory T cells in normal pregnancies. In addition, we discuss the association between autophagy and regulatory T cells in the development of preeclampsia based on reports on the role of autophagy in autoimmune diseases.
Journals
2024 EN
Fischer Leonardo Wensing · Nunes Marina · Mendes Talita Biude
+4 more
Abstract Background After the Coronavirus Disease pandemic, depression became more present, including in adolescents. Escitalopram, a selective serotonin reuptake inhibitor, was approved in 2009 for treatment of the major depressive disorder, both in children and adolescents. The undesirable effects of antidepressants on sexual dysfunction are usually underestimated. Aims To investigate the effects of chronic mild stress, induced from peripuberty up to adulthood, on male sexual behavior parameters, with or without the escitalopram treatment, using rats as experimental model in a translational study. Materials and methods Forty‐four peripubertal male rats were distributed into four groups: Sham control, escitalopram, stress, and stress + escitalopram. The chronic mild stress consisted of nine different stressors randomly applied one per day, for 8 weeks (from 41 to 97 days postpartum). Escitalopram therapy by gavage (10 mg/kg) started at 70 days postpartum and lasted for 4 weeks. The male sexual behavior parameters were evaluated at 114 days postpartum. After that, euthanasia was performed for blood and testis collection. Histopathology of the testes and plasmatic testosterone level were carried out. Results There was a reduction in sexual activity and motivation in rats exposed to the stress protocol, which were treated or not with escitalopram, as well as an increase in the total number of mounts in animals exposed to the stress and treated with escitalopram. The testosterone levels were lower in animals exposed to the stress, which were or not treated with escitalopram (stress and stress + escitalopram). The frequency of histologically normal seminiferous tubule sections was lower in animals that were exposed to the stress and/or received escitalopram (escitalopram, stress, and stress + escitalopram). Conclusion Chronic mild stress induced from peripuberty, associated or not to escitalopram treatment, altered the testosterone levels and testicular histoarchitecture and seems to be related to the reduction in male sexual motivation.
Journals
2024 EN
Marcucci Lorenzo · Nogara Leonardo · Canato Marta
+9 more
Aim Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca 2+ ([Ca 2+ ] cyto ) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix‐free calcium concentration ([Ca 2+ ] mito ). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency. Methods We determined the free Ca 2+ redistribution during a 2 s 60 Hz tetanic stimulation in the sarcoplasmic reticulum, cytosol, and mitochondria. Via a reaction–diffusion Ca 2+ model, we quantitatively evaluated mitochondrial uptake and storage capacity requirements to compensate for PV lack and analyzed possible extracellular export. Results [Ca 2+ ] mito during tetanic stimulation is greater in knock‐out (KO) (1362 ± 392 nM) than in wild‐type (WT) (855 ± 392 nM), p < 0.05. Under the assumption of a non‐linear intramitochondrial buffering, the model predicts an accumulation of 725 μmoles/ L fiber (buffering ratio 1:11 000) in KO, much higher than in WT (137 μmoles/ L fiber , ratio 1:4500). The required transport rate via mitochondrial calcium uniporter (MCU) reaches 3 mM/s, compatible with available literature. TEM images of calcium entry units and Mn 2+ quenching showed a greater capacity of store‐operated calcium entry in KO compared to WT. However, levels of [Ca 2+ ] cyto during tetanic stimulation were not modulated to variations of extracellular calcium. Conclusions The model‐based analysis of experimentally determined calcium distribution during tetanic stimulation showed that mitochondria can act as a buffer to compensate for the lack of PV. This result contributes to a better understanding of mitochondria's role in modulating [Ca 2+ ] cyto in skeletal muscle fibers.
Journals
2024 EN
Coelho Marta Paula Pereira · Vries Thais Pontello · Pires Aline Marcos
+8 more
Summary Background Results of studies evaluating the effect of viral eradication following direct‐acting antiviral (DDA) therapy on skeletal muscle mass of patients with chronic hepatitis C (CHC) are scarce. Aim To assess the components of sarcopenia (low muscle mass, low muscle strength and low physical performance) in a cohort of CHC individuals before and after DAA therapy. Methods We performed a longitudinal study of patients with CHC who underwent body composition assessment before (T0), and at 12 (T1) and 48 (T2) weeks after DDA therapy. Bioelectrical Impedance Analysis was used to assess skeletal mass muscle (SM) and phase angle (PhA). SM index (SMI) was calculated by dividing the SM by squared height. Muscle function was evaluated by hand grip strength (HGS) and timed up‐and‐go (TUG) test. Mixed‐effects linear regression models were fitted to SMI, HGS and physical performance and were used to test the effect of HCV eradication by DAA. Results 62 outpatients (mean age, 58.6 ± 10.8 years; 58% with compensated cirrhosis) were included. Significant decreases in liver fibrosis markers and an increase of 0.20 and 0.22 kg/m 2 in the SMI were observed at T1 and T2. Following DAA therapy, an increase of one unit of PhA was associated with a reduction of 0.38 min in TUG. Conclusion HCV eradication with DAA therapy was associated with a dynamic reduction of non‐invasive markers of liver fibrosis and increased muscle mass in 62 patients with CHC who had an undetectable HCV load at 12 weeks after completion of antiviral treatment.
Journals
2024 EN
Tada Toshifumi · Kumada Takashi · Hiraoka Atsushi
+40 more
Summary Background Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC). Aims To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real‐world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial. Methods A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non‐IMbrave150 group). Results Median progression‐free survival (PFS) in the IMbrave150 and non‐IMbrave150 groups was 7.4 months and 5.6 months ( p = 0.002). Multivariable analysis revealed that non‐B, non‐C HCC aetiology (hazard ratio [HR], 1.173), α‐fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin–bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non‐Imbrave150 groups was 26.5 and 18.8 months ( p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α‐fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a. Conclusions Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival.
Journals
2024 EN
Hatanaka Takeshi · Kakizaki Satoru · Hiraoka Atsushi
+40 more
Summary Aim This study aims to investigate the predictive factors for conversion therapy in patients with unresectable hepatocellular carcinoma (uHCC) and to evaluate the prognosis of conversion cases by comparing them with partial response (PR) and complete response (CR) cases. Methods In this retrospective multicentre study, we included a total of 946 uHCC patients treated with atezolizumab and bevacizumab (Atez/Bev) from September 2020 to September 2023. Results Out of the patients, 43 (4.5%) received conversion therapy following Atez/Bev treatment. The overall response rate was 65.1% and 23.7% in the conversion and non‐conversion group, respectively, with a statistical significance ( p < 0.001). Multivariate analyses identified that BCLC stage B or an earlier stage ( p = 0.045), absence of macrovascular invasion and extrahepatic spread ( p = 0.045), and a low value of neutrophil to lymphocyte ratio ( p = 0.04) were significantly favourable predictive factors associated with conversion therapy. The conversion group showed significantly better survival compared to the non‐conversion group ( p < 0.001). In the landmark analysis at 6, 12 and 18 months, the conversion group exhibited better survival compared to PR patients in the non‐conversion group ( p = 0.04, 0.01 and 0.03, respectively) and there were no significant differences in the overall survival (OS) between the conversion group and patients who achieved a CR ( p = 0.7, 1.0 and 0.3, respectively). Conclusions Patients with low tumour burden and low value of NLR were more likely to undergo conversion therapy. The OS of patients undergoing conversion therapy showed better survival compared to those achieving PR and was comparable to those with CR patients. Conversion therapy could be considered if feasible.
Journals
2024 EN
Yamamoto Priscila Akemi · Vozmediano Valvanera · Cristofoletti Rodrigo
+8 more
Aims A population‐based pharmacokinetic (PK) modeling approach (PopPK) was used to investigate the impact of Roux‐en‐Y gastric bypass (RYGB) on the PK of ( R )‐ and ( S )‐carvedilol. We aimed to optimize carvedilol dosing for these patients utilizing a pharmacokinetic/pharmacodynamic (PK/PD) link model. Methods PopPK models were developed utilizing data from 52 subjects, including nonobese, obese, and post‐ RYGB patients who received rac ‐ carvedilol orally. Covariate analysis included anthropometric and laboratory data, history of RYGB surgery, CYP2D6 and CYP3A4 in vivo activity, and relative intestinal abundance of major drug‐ metabolizing enzymes and transporters. A direct effect inhibitory E max pharmacodynamic model was linked to the PK model of ( S )‐ carvedilol to simulate the changes in exercise‐ induced heart rate. Results A 2‐compartmental model with linear elimination and parallel first‐order absorptions best described ( S )‐carvedilol PK. RYGB led to a twofold reduction in relative oral bioavailability compared to nonoperated subjects, along with delayed absorption of both enantiomers. The intestinal ABCC2 mRNA expression increases the time to reach the maximum plasma concentration. The reduced exposure (AUC) of (S)‐carvedilol post‐RYGB corresponded to a 33% decrease in the predicted area under the effect curve (AUEC) for the 24‐hour β‐blocker response. Simulation results suggested that a 50‐mg daily dose in post‐RYGB patients achieved comparable AUC and AUEC to 25‐mg dose in nonoperated subjects. Conclusion Integrated PK/PD modeling indicated that standard dosage regimens for nonoperated subjects do not provide equivalent β‐blocking activity in RYGB patients. This study highlights the importance of personalized dosing strategies to attain desired therapeutic outcomes in this patient cohort.