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1.
World J Hepatol ; 16(6): 900-911, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38948438

RESUMO

Achievement of a 'clinical cure' in chronic hepatitis B (CHB) implies sustained virological suppression and immunological control over the infection, which is the ideal treatment goal according to domestic and international CHB management guidelines. Clinical practice has shown encouraging results for specific patient cohorts using tailored treatment regimens. These regimens incorporate either nucleos(t)ide analogs, immunomodulatory agents such as pegylated interferon α, or a strategic combination of both, sequentially or concurrently administered. Despite these advancements in the clinical handling of hepatitis B, achieving a clinical cure remains elusive for a considerable subset of patients due to the number of challenges that preclude the realization of optimal treatment outcomes. These include, but are not limited to, the emergence of antiviral resistance, incomplete immune recovery, and the persistence of covalently closed circular DNA. Moreover, the variance in response to interferon therapy and the lack of definitive biomarkers for treatment cessation also contribute to the complexity of achieving a clinical cure. This article briefly overviews the current research progress and existing issues in pursuing a clinical cure for hepatitis B.

2.
Cureus ; 16(4): e58550, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38957820

RESUMO

Background Due to the emergence of new COVID-19 mutations and an increase in re-infection rates, it has become an important priority for the medical community to identify the factors affecting the short- and long-term survival of patients. This study aimed to determine the risk factors of short- and long-term survival in patients with COVID-19 based on mixture and non-mixture cure models. Methodology In this study, the data of 880 patients with COVID-19 confirmed with polymerase chain reaction in Fereydunshahr city (Isfahan, Iran) from February 20, 2020, to December 21, 2021, were gathered, and the vital status of these patients was followed for at least one year. Due to the high rate of censoring, mixture and non-mixture cure models were applied to estimate the survival. Akaike information criterion values were used to evaluate the fit of the models. Results In this study, the mean age of the patients was 48.9 ± 21.23 years, and the estimated survival rates on the first day, the fourth day, the first week, the first month, and at one year were 0.997, 0.982, 0.973, 0.936, and 0.928, respectively. Among the parametric models, the log-logistic mixed cure model with the logit link, which showed the lowest Akaike information criterion value, demonstrated the best fit. The variables of age and prescribed medication type were significant predictors of long-term survival, while occupation was influential in the short-term survival of patients. Conclusions According to the results of this study, it can be concluded that elderly patients should observe health protocols more strictly and consider receiving booster vaccine doses. The log-logistic cure model with a logit link can be used for survival analysis in COVID-19 patients, a fraction of whom have long-term survival.

4.
Arch Esp Urol ; 77(5): 479-490, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38982776

RESUMO

OBJECTIVE: Meta-analysis was conducted to compare and evaluate the efficacy and safety of tension-free vaginal tape (TVT), outside-in trans-obturator tape (TOT), inside-out tension-free vaginal tape-obturator (TVT-O) and transvaginal tension-free urethral sling surgery (TVT-S) in the treatment of female stress urinary incontinence (SUI). METHODS: A computer-based systematic search of the PubMed, The Cochrane Library, Medline, Embase, Web of Science and ScienceDirect databases for randomised controlled trials (RCTs) comparing TVT, TOT, TVT-O and TVT-S for the treatment of SUI was performed from the time of library construction to November 2023. Two investigators performed data extraction and quality evaluation of the included RCTs, extracting information including the follows: First author, time of publication, intervention, sample size, age, duration of follow-up and objective cure rate, subjective cure rate, dyspareunia, vaginal mucosal perforation, urinary tract infection, sling exposure and postoperative thigh pain/groin pain. Review Manager (RevMan) 5.4 was used for data processing. RESULTS: A total of 14 RCTs with 2665 patients were included. Meta-analysis showed no statistically significant differences in objective cure rate, urinary tract infection, sling exposure and postoperative thigh pain/groin pain. The subjective cure rate of TVT was higher than that of TOT (odds ratio (OR), 95% confidence interval (CI) = 1.37 (1.02, 1.84), p = 0.03); The incidence of TVT-O voiding difficulty was lower than that of TVT (OR, 95% CI = 2.94 (1.20, 7.20), p = 0.02); And the incidence of vaginal mucosal perforation of TOT was lower than that of TVT (OR, 95% CI = 0.11 (0.02, 0.61), p = 0.01). CONCLUSIONS: The four surgical procedures, TVT, TOT, TVT-O and TVT-S, were relatively similar in terms of SUI outcomes. TVT had a higher subjective cure rate than TOT and a higher incidence of postoperative dyspareunia and vaginal mucosal perforation.


Assuntos
Slings Suburetrais , Incontinência Urinária por Estresse , Procedimentos Cirúrgicos Urológicos , Feminino , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Slings Suburetrais/efeitos adversos , Resultado do Tratamento , Incontinência Urinária por Estresse/cirurgia , Procedimentos Cirúrgicos Urológicos/métodos , Procedimentos Cirúrgicos Urológicos/efeitos adversos
5.
ESMO Open ; 9(7): 103635, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39043021

RESUMO

BACKGROUND: The number and projections of cancer survivors are necessary to meet the healthcare needs of patients, while data on cure prevalence, that is, the percentage of patients who will not die of cancer by time since diagnosis, are lacking. MATERIALS AND METHODS: Data from Italian cancer registries (duration of registration ranged from 9 to 40 years, with a median of 22 years) covering 47% of the population were used to calculate the limited-duration prevalence, the complete prevalence in 2018, projections to 2030, and cure prevalence, by cancer type, sex, age, and time since diagnosis. RESULTS: A total of 3 347 809 people were alive in Italy in 2018 after a cancer diagnosis, corresponding to 5.6% of the resident population. They will increase by 1.5% per year to 4 012 376 in 2030, corresponding to 6.9% of the resident population, 7.6% of women and ∼22% after age 75 years. In 2030, more than one-half of all prevalent cases (2 million) will have been diagnosed by ≥10 years. Those with breast (1.05 million), prostate (0.56 million), or colorectal cancers (0.47 million) will be 52% of all prevalent patients. Cure prevalence was 86% for all patients alive in 2018 (87% for patients with breast cancer and 99% for patients with thyroid or testicular cancer), increasing with time since diagnosis to 93% for patients alive after 5 years and 96% after 10 years. Among patients who survived at least 5 years, the excess risk of death (1 - cure prevalence) was <5% for patients with most cancer types except for those with cancers of the breast (8.3%), lung (11.1%), kidney (13.2%), and bladder (15.5%). CONCLUSIONS: Study findings encourage the implementation of evidence-based policies aimed at improving long-term clinical follow-up and rehabilitation of people living after cancer diagnosis throughout the course of the disease. Updated estimates of complete prevalence are important to enhance data-driven cancer control planning.

6.
Front Pharmacol ; 15: 1403805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39035984

RESUMO

Introduction: Chronic hepatitis B (CHB) is a worldwide infectious disease caused by hepatitis B virus (HBV). Optimizing antiviral treatment strategies could improve the functional cure (FC) rate of patients with CHB. This study aims to systematically review the FC rate of the de novo combination of nucleos(t)ide analogs (NAs) and pegylated interferon α (PEG-IFNα) versus that of PEG-IFNα monotherapy for CHB. Methods: Databases were searched until 31 December 2023. Selected studies included randomized controlled trials on the de novo combination of NAs and PEG-IFNα versus PEG-IFNα monotherapy for 48 weeks in patients with CHB to achieve FC, which was defined as hepatitis B surface antigen (HBsAg) loss and/or HBsAg seroconversion. Meta-analysis was conducted in accordance with the efficacy at the end of treatment and different time points during follow-up. Results: A total of 10 studies, encompassing 2,339 patients in total, were included. Subgroup analysis was conducted in accordance with whether first-line NAs were used. It found no statistically significant difference between HBsAg loss and HBsAg seroconversion at the end of treatment. Serum HBV DNA <500 copies/mL significantly differed between the two groups at the end of treatment and did not significantly differ during follow-up. Meanwhile, HBsAg loss and HBsAg seroconversion showed statistically significant differences at 24 weeks of follow-up. By contrast, no statistically significant difference was found in HBsAg loss at 48 weeks of follow-up. Discussion: Without distinguishing the eligible preponderant population, the efficacy of the de novo combination of NAs and PEG-IFNα in treating patients with CHB was not superior to that of PEG-IFNα monotherapy. Systematic Review Registration: PROSPERO, identifier CRD42022325239.

7.
J Clin Med ; 13(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38999294

RESUMO

Addressing the dysfunctions of all brain cell types in Alzheimer's disease (AD) should cure the dementia, an objective that might be achieved by GLP-1 agonist drugs, because receptors for GLP-1 are present in all of the main brain cell types, i.e., neurons, oligodendroglia, astroglia, microglia, endothelial cells and pericytes. This article describes the benefits provided to all of those brain cell types by GLP-1 agonist drugs. The article uses studies in humans, not rodents, to describe the effect of GLP-1 agonists upon cognition, because rodents' brains differ from those of humans in so many ways that results from rodent studies may not be totally transferable to humans. Commercially available GLP-1 agonists have mostly shown either positive effects upon cognition or no effects. One important reason for no effects is a reduced rate of entering brain parenchyma. Dulaglutide has the greatest entry to brain, at 61.8%, among the available GLP-1 agonists, and seems to offer the best likelihood for cure of AD. Although there is only one study of cognition that used dulaglutide, it was randomized, placebo controlled, and very large; it involved 8828 participants and showed significant benefit to cognition. A clinical trial to test the hypothesis that dulaglutide may cure AD should have, as its primary outcome, a 30% greater cure rate of AD by dulaglutide than that achieved by an equipoise arm of, e.g., lithium plus memantine.

8.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(6): 1182-1187, 2024 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-38977349

RESUMO

OBJECTIVE: To explore the applicable conditions of the Cox-TEL (Cox PH-Taylor expansion adjustment for long-term survival data) method for analysis of survival data that contain cured patients. METHODS: The simulated survival data method based on Weibull distribution was used to simulate and generate the survival data with different cure rates, censored rates, and cure rate differences. The Cox-TEL method was used for analysis of the generated simulation data, and its performance was evaluated by calculating its type Ⅰ error and power. RESULTS: Almost all the type Ⅰ error of the hazard ratios (HRs) obtained by the Cox-TEL method under different conditions were slightly greater than 0.05, and this method showed a good test power for estimating the HRs for data with a large sample size and a large difference in proportions (DPs). For the data of cured patients, the type Ⅰ error of the DPs obtained by the Cox-TEL method was well around 0.05, and its test power was robust in most of the scenarios. CONCLUSION: The Cox-TEL method is effective for analyzing data of uncured patients and obtaining reliable HRs for most of the survival data with a sample size, a low censored rates, and a large difference in cure rates. The method is capable of accurately estimating the DPs regardless of the sample size, censored rates, or the cure rates.


Assuntos
Simulação por Computador , Modelos de Riscos Proporcionais , Humanos , Reprodutibilidade dos Testes , Análise de Sobrevida , Tamanho da Amostra
9.
Pulm Pharmacol Ther ; 86: 102315, 2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39009240

RESUMO

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of inhaled antibiotics for adults with pneumonia by meta-analysis. METHODS: Literature retrieval was completed through five databases (PubMed, Embase, Cochrane Library, Web of Science and Scopus) by the deadline of May 31, 2024. The process of study selection and data extraction were performed independently by two reviewers. The quality of observational studies and randomized controlled trial (RCT) studies were evaluated by Newcastle Ottawa scale and Jadad scale, respectively. The primary outcomes included mortality, clinical cure, and microbiological cure. Secondary outcomes were recurrence and renal impairment. RESULTS: There were 30 studies were analyzed, including 12 RCT studies and 18 observational studies. Inhaled antibiotics did not significantly reduce mortality in RCT studies (odds ratio (OR) = 1.06, 95 % confidence interval (CI): 0.80-1.41). Inhaled antibiotics were associated with higher rates of clinical cure (OR = 1.47 95%CI: 0.82-2.66 in RCT studies and OR = 2.09, 95%CI: 1.36-3.21 in observational studies) and microbiological cure (OR = 7.00 in RCT studies and OR = 2.20 in observational studies). Subgroup analysis showed patients received inhaled antibiotics combined with intravenous administration and inhaled amikacin had better improvements of mortality, clinical cure and microbiological cure. Inhaled antibiotics were not associated with recurrence. The pooled OR of renal impairment were 0.65 (95%CI: 0.27-1.13; I-squared = 43.5 %, P = 0.124) and 0.63(95%CI: 0.26-1.11; I-squared = 69.0 %, P = 0.110) in RCT studies and observational studies, respectively. CONCLUSIONS: Inhaled antibiotics decreased risk of renal impairment and achieved significant improvements of clinical and microbiological cure in patients with pneumoniae.

10.
Cureus ; 16(6): e62339, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39006628

RESUMO

Occam's razor, the principle of parsimony, is frequently employed in medicine to derive a single diagnosis from a patient's myriad symptoms. Conversely, Hickam's dictum, which embraces the principle of plenitude by considering multiple diagnoses for a patient's presentation, is often underutilized or not as widely recognized as Occam's razor. The application of Hickam's dictum is particularly crucial when evaluating nonspecific symptoms such as fatigue, which can manifest in various diseases. This report describes the case of a 72-year-old man with a history of functional cure for hepatitis B who presented with chronic fatigue and hyponatremia. Initially, he was diagnosed with non-functional pituitary macroadenoma and panhypopituitarism. Two months following pituitary surgery, the onset of dyspepsia and the recurrence of fatigue revealed metastatic tumors in the liver, stomach, pancreas, left adrenal gland, and peri-pancreatic lymph nodes. A liver biopsy confirmed the diagnosis of hepatocellular carcinoma. This case highlights the importance of considering multiple, potentially co-existing conditions based on the patient's symptoms and risk factors to complete the thorough diagnoses. Additionally, it emphasizes the need to remain vigilant regarding the risk of liver cancer in patients with a history of chronic hepatitis B infection, irrespective of a functional cure.

11.
J Oral Sci ; 66(3): 182-188, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39010166

RESUMO

PURPOSE: To evaluate the influence of the polymerization distance of monowave and polywave light curing units (LCUs) on the measured irradiance relative to the value reported by the manufacturer in relation to the physical properties of resin-based composites (RBCs). METHODS: Four LCUs were used: one monowave and three polywave. The irradiance was measured with a digital radiometer. Depth of cure (DC) and flexural strength (FS) tests were performed according to ISO 4049:2019 at polymerization distances of 0 mm and 5 mm. RESULTS: The irradiance of all LCUs was higher than that reported by the manufacturer (>25-64%). The irradiance of the four LCUs was reduced when polymerization was performed at between 0 to 5 mm (paired t-test, P < 0.001). The DC at 0 mm was similar in all groups but was significantly decreased at 5 mm distance (ANOVA P < 0.001). FS showed differences among the LCUs at 0 mm (ANOVA P < 0.001) and was affected by the polymerization distance. The elastic modulus was unaffected by the LCU used or the distance (ANOVA P > 0.001). CONCLUSIONS: The LCU must be positioned as near as possible to RBCs during the polymerization process, as increased distance negatively affects the depth of cure and flexural strength.


Assuntos
Resinas Compostas , Lâmpadas de Polimerização Dentária , Polimerização , Resinas Compostas/química , Teste de Materiais , Resistência à Flexão , Módulo de Elasticidade
12.
J Microbiol Biol Educ ; : e0000924, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39012127

RESUMO

Professional development of scientists is enhanced by training students in responsible conduct of research earlier in their careers. One aspect of responsible conduct of research is authorship ethics, which concerns granting of credit to those who make intellectual contributions to the research. The activity discussed in this article emphasizes how authorship ethics can be integrated with Course-based Undergraduate Research Experience (CURE) and includes an adaption that could also be used for independent research students. The activity allows students to reflect upon inequalities and problems seen in scientific authorship, including gender bias, failure to credit effort (ghostwriters), and inclusion of authors that did not meaningfully contribute to the work (honorary/gift authorship). Themes seen in student reflections on how they could demonstrate ethics in authorship included: determining authorship by contribution, appropriate attributions on curriculum vitas (CV) and posters, different credit levels, understanding authorship criteria, and tracking contributions. Themes seen in student reflections on the importance of authorship were proper authorship credit distribution, authorship impacting career opportunities, and accountability in research. In the activity, students also created attributions for a poster to be presented from their research. We found that most students were able to create attributions that were correctly formatted, included the same authors, and positioned authors in the same order as other group members, matching what was presented on the finalized poster. We found that students' reflection on authorship and this professionalization of their activities in their CURE led to modest increases in their view of themselves as scientists.

13.
Antiviral Res ; 228: 105955, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964614

RESUMO

High levels of hepatitis B virus (HBV) surface antigen (HBsAg) in the blood of chronic HBV carriers are considered to drive the exhaustion of antigen-specific T and B lymphocytes and thus responsible for the persistence of infection. Accordingly, therapeutic elimination of HBsAg may facilitate the activation of adaptive antiviral immune responses against HBV and achieve a functional cure of chronic hepatitis B. We discovered recently that an amphipathic alpha helix spanning W156 to R169 of HBV small envelope (S) protein plays an essential role in the morphogenesis of subviral particles (SVPs) and metabolism of S protein. We thus hypothesized that pharmacological disruption of SVP morphogenesis may induce intracellular degradation of S protein and reduce HBsAg secretion. To identify inhibitors of SVP biogenesis, we screened 4417 bioactive compounds with a HepG2-derived cell line expressing HBV S protein and efficiently secreting small spherical SVPs. The screen identified 24 compounds that reduced intracellular SVPs and secreted HBsAg in a concentration-dependent manner. However, 18 of those compounds inhibited the secretion of HBsAg and HBeAg in HBV replicon transfected HepG2 cells at similar efficiency, suggesting each of those compounds may disrupt a common cellular function required for the synthesis and/or secretion of these viral proteins. Interestingly, lycorine more efficiently inhibited the secretion of HBsAg in HepG2 cells transfected with HBV replicons, HepG2.2.15 cells and HBV infected - HepG2 cells expressing sodium taurocholate cotransporting polypeptide (NTCP). The structure activity relationship and antiviral mechanism of lycorine against HBV have been determined.


Assuntos
Antivirais , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Humanos , Vírus da Hepatite B/efeitos dos fármacos , Antivirais/farmacologia , Antígenos de Superfície da Hepatite B/metabolismo , Células Hep G2 , Montagem de Vírus/efeitos dos fármacos , Vírion/efeitos dos fármacos , Descoberta de Drogas , Replicação Viral/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Proteínas do Envelope Viral/metabolismo , Antígenos E da Hepatite B/metabolismo
14.
Eur J Cancer ; 208: 114187, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39013266

RESUMO

BACKGROUND: To estimate net survival and cancer cure fraction (CF), i.e. the proportion of patients no longer at risk of dying from cancer progression/relapse, a clear distinction needs to be made between mortality from cancer and from other causes. Conventionally, CF is estimated assuming no excess mortality compared to the general population. METHODS: A new modelling approach, that corrects for patients' extra risk of dying (RR) from causes other than the diagnosed cancer, was considered to estimate both indicators. We analysed EUROCARE-6 data on head and neck (H&N), colorectal, and breast cancer patients aged 40-79, diagnosed from 1998 to 2002 and followed-up to 31/12/2014, provided by 65 European cancer registries. FINDINGS: Young male H&N cancer patients have 4 times the risk of dying from other causes than their peers, this risk decreases with age to 1.6. Similar results were observed for female. We observed an absolute increase in CF of 30 % using the new model instead of the conventional one. For colorectal cancer, CF with the new model increased by a maximum of 3 % for older patients and the RR ranged from 1 to 1.2 for both sexes. CF of female breast cancer ranged from 73 % to 79 % using the new cure model, with RR between 1.2 and 1.4. INTERPRETATION: Not considering a RR> 1 leads to underestimate the proportion of patients not bound to die of their diagnosed cancer. Estimates of cancer mortality risk have an important impact on patients' quality of life.

15.
Front Immunol ; 15: 1392256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38887283

RESUMO

Introduction: The assessment of tuberculosis (TB) treatment outcomes predominantly relies on sputum culture conversion status. To enhance treatment management, it is crucial to identify non-sputum-based biomarkers that can predict unfavorable outcomes. Cytokines are widely studied as diagnostic biomarkers for active TB. However, their potential as indicators for unfavorable treatment outcomes remains uncertain. Methodology: This study was conducted within a well-characterized cohort comprising newly diagnosed patients with drug-sensitive pulmonary TB, confirmed through sputum smear and culture positivity. Our objective was to elucidate the TB antigen-stimulated cytokine profile at pre-treatment and at 2 months into anti-TB treatment (ATT) in patients with unfavorable treatment outcomes (cases, n = 27) in comparison to recurrence-free, microbiologically cured controls (n = 31). Whole blood was stimulated with TB antigens using the QuantiFERON In-tube gold method, and plasma supernatants were subjected to a panel of 14 cytokine measurements. Results: In our study, pre-treatment analysis revealed that eight cytokines (IL-2, IFN-γ, TNF-α, IL-6, IL-10, IL-17A, IL-18, and GM-CSF) were significantly elevated at baseline in cases compared to cured controls, both in unstimulated conditions and following TB antigen (CFP10, ESAT6, and TB7.7) stimulation. A similar pattern was observed at the 2-month mark of ATT, with eight cytokines (IL-2, IL-10, IL-13, IFN-γ, IL-6, IL-12p70, IL-17A, and TNF-α) showing significant differences between the groups. Importantly, no variations were detected following mitogen stimulation, underscoring that these distinctive immune responses are primarily driven by TB-specific antigens. Conclusion: Our findings indicate that individuals with unfavorable TB treatment outcomes display a characteristic cytokine profile distinct from TB-cured patients, even before commencing ATT. Therefore, the levels of specific cytokine pre-treatment and at the 2-month point in the course of treatment may serve as predictive immune markers for identifying individuals at risk of unfavorable TB treatment outcomes, with these responses being predominantly influenced by TB-specific antigens.


Assuntos
Antígenos de Bactérias , Antituberculosos , Biomarcadores , Citocinas , Mycobacterium tuberculosis , Tuberculose Pulmonar , Humanos , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico , Citocinas/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Biomarcadores/sangue , Antígenos de Bactérias/imunologia , Resultado do Tratamento , Antituberculosos/uso terapêutico , Mycobacterium tuberculosis/imunologia , Idoso
16.
Polymers (Basel) ; 16(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891440

RESUMO

The frontal polymerization (FP) of carbon/epoxy (C/Ep) composites is investigated, considering FP as a viable route for the additive manufacturing (AM) of thermoset composites. Neat epoxy (Ep) resin-, short carbon fiber (SCF)-, and continuous carbon fiber (CCF)-reinforced composites are considered in this study. The evolution of the exothermic reaction temperature, polymerization frontal velocity, degree of cure, microstructures, effects of fiber concentration, fracture surface, and thermal and mechanical properties are investigated. The results show that exothermic reaction temperatures range between 110 °C and 153 °C, while the initial excitation temperatures range from 150 °C to 270 °C. It is observed that a higher fiber content increases cure time and decreases average frontal velocity, particularly in low SCF concentrations. This occurs because resin content, which predominantly drives the exothermic reaction, decreases with increased fiber content. The FP velocities of neat Ep resin- and SCF-reinforced composites are seen to be 0.58 and 0.50 mm/s, respectively. The maximum FP velocity (0.64 mm/s) is observed in CCF/Ep composites. The degree of cure (αc) is observed to be in the range of 70% to 85% in FP-processed composites. Such a range of αc is significantly low in comparison to traditional composites processed through a long cure cycle. The glass transition temperature (Tg) of neat epoxy resin is seen to be approximately 154 °C, and it reduces slightly to a lower value (149 °C) for SCF-reinforced composites. The microstructures show significantly high void contents (12%) and large internal cracks. These internal cracks are initiated due to high thermal residual stress developed during curing for non-uniform temperature distribution. The tensile properties of FP-cured samples are seen to be inferior in comparison to autoclave-processed neat epoxy. This occurs mostly due to the presence of large void contents, internal cracks, and a poor degree of cure. Finally, a highly efficient and controlled FP method is desirable to achieve a defect-free microstructure with improved mechanical and thermal properties.

17.
Polymers (Basel) ; 16(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38891487

RESUMO

This article proposes a numerical routine to predict the residual stresses developing in an epoxy component during its curing. The scaling of viscoelastic properties with the temperature and the degree of conversion is modeled, adopting a mathematical formulation that considers the concurrent effects of curing and structural relaxation on the epoxy's viscoelastic relaxation time. The procedure comprises two moduli: at first, the thermal-kinetical problem is solved using the thermal module of Ansys and a homemade routine written in APDL, then the results in terms of temperature and the degree of conversion profiles are used to evaluate the viscoelastic functions, and the structural problem is solved in the mechanical module of Ansys, allowing the residual stresses calculation. The results show that the residual stresses mainly arise during cooling and scale with the logarithm of the Biot number.

18.
Viruses ; 16(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38932203

RESUMO

BACKGROUND: Although antiretroviral therapy (ART) effectively halts disease progression in HIV infection, the complete eradication of the virus remains elusive. Additionally, challenges such as long-term ART toxicity, drug resistance, and the demanding regimen of daily and lifelong adherence required by ART highlight the imperative need for alternative therapeutic and preventative approaches. In recent years, broadly neutralizing antibodies (bNAbs) have emerged as promising candidates, offering potential for therapeutic, preventative, and possibly curative interventions against HIV infection. OBJECTIVE: This review aims to provide a comprehensive overview of the current state of knowledge regarding the passive immunization of bNAbs in HIV-1-infected individuals. MAIN FINDINGS: Recent findings from clinical trials have highlighted the potential of bNAbs in the treatment, prevention, and quest for an HIV-1 cure. While monotherapy with a single bNAb is insufficient in maintaining viral suppression and preventing viral escape, ultimately leading to viral rebound, combination therapy with potent, non-overlapping epitope-targeting bNAbs have demonstrated prolonged viral suppression and delayed time to rebound by effectively restricting the emergence of escape mutations, albeit largely in individuals with bNAb-sensitive strains. Additionally, passive immunization with bNAb has provided a "proof of concept" for antibody-mediated prevention against HIV-1 acquisition, although complete prevention has not been obtained. Therefore, further research on the use of bNAbs in HIV-1 treatment and prevention remains imperative.


Assuntos
Anticorpos Neutralizantes , Anticorpos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/imunologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/imunologia , Anticorpos Anti-HIV/imunologia , Anticorpos Anti-HIV/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/uso terapêutico , Imunização Passiva/métodos , Anticorpos Amplamente Neutralizantes/imunologia , Anticorpos Amplamente Neutralizantes/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Animais
19.
Dent Mater J ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38945865

RESUMO

This study investigated the usefulness of a dental laboratory polymerization unit with light-emitting diode (LED) as a light source. The depth of cure (n=15), water absorption and solubility (n=9) of two indirect composite materials (Cesead N and Solidex Hardura) were evaluated by five dental laboratory polymerization units (LED Cure Master, Twinkle LED, α-Light V, α-Light II, and Hyper LII). Statistical analysis was performed by one-way ANOVA and Tukey test or non-parametric tests. Comparison of light sources for curing depth showed that metal halide had the highest value, followed by the LED group with similar values, and halogen lamps with the lowest value. The water absorption and solubility of the composite specimens polymerized with the three LED laboratory polymerization units were within the ISO recommended limit.

20.
Polymers (Basel) ; 16(12)2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38931992

RESUMO

Pultrusion is a highly efficient continuous process to manufacture advanced fiber-reinforced composites. The injection pultrusion variant permits a higher control of the resin flow, enabling the manufacturing of a high reinforcement volume fraction. Moreover, it reduces the emission of volatile compounds that are dangerous for the operators and for the working environment. The present study proposes an experimental analysis of injection pultrusion in three different operative conditions. In particular, the activity focused on the effects of the temperature setup on the thermochemical and rheological behaviors of the resin system and on the interaction between the processed materials and the pultrusion die wall. The setup of the parameters was selected to evidence the behavior of the viscous interaction during the thermoset transition to the solid state, which is particularly challenging due to the localization of high adhesive forces related to the sharp increase in resin viscosity. Microscope observations of the cross-sections were performed to discuss the effects of the process parameters.

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