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1.
Braz J Infect Dis ; 28(3): 103768, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38851212

RESUMO

We report an autochthonous case of mild unifocal chronic pulmonary paracoccidioidomycosis in a 48-year-old previously healthy woman with no history of possible environmental exposures in endemic rural areas, supposedly resulting from reactivation of a latent pulmonary focus secondary to the use of methotrexate for the control of Chikungunya arthropathy. Laboratory investigation ruled out other immunosuppression. Her only symptoms were a dry cough and chest pain. Diagnosis confirmed by needle lung biopsy. There were no abnormalities on physical examination nor evidence of central nervous system involvement. MRI of the total abdomen showed no involvement of other organs. Computed chest tomography showed a favorable evolution under the use of itraconazole (200 mg/day). Different tomographic presentations findings are highlighted when performed before and after treatment. CONCLUSIONS: PCM should be considered even in a woman without a history of consistent environmental exposure and in a non-endemic geographic area.


Assuntos
Pneumopatias Fúngicas , Metotrexato , Paracoccidioidomicose , Humanos , Feminino , Paracoccidioidomicose/tratamento farmacológico , Pessoa de Meia-Idade , Metotrexato/uso terapêutico , Metotrexato/efeitos adversos , Pneumopatias Fúngicas/tratamento farmacológico , Doença Crônica , Itraconazol/uso terapêutico , Tomografia Computadorizada por Raios X , Antifúngicos/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico
2.
Eur J Case Rep Intern Med ; 11(6): 004477, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846671

RESUMO

Background: Small cell lung cancer is an aggressive tumor with a poor prognosis that requires prompt treatment. While radiotherapy may enhance survival when superior vena cava syndrome is present, radiation therapy-induced pericardial disease can be a potential complication. Case Report: A 55-year-old man, who recently underwent radiotherapy for stage IV small-cell lung cancer complicated by superior vena cava syndrome, presented with chest pain and dyspnea. In the emergency room, he was dyspneic, hypotensive, and tachycardic. Pulmonary auscultation revealed the absence of lung sounds on the right. The initial electrocardiogram showed ST-segment elevation in lateral leads and in lead DII, with reciprocal changes in lead DIII. A bedside transthoracic echocardiogram revealed cardiac tamponade and emergent pericardiocentesis was performed, removing 500 ml of purulent fluid, resulting in an immediate clinical improvement. Thoracentesis was also performed, showing no empyema. Large spectrum empirical antibiotic therapy was started. Cultures from the pericardial fluid and peripheral blood grew multi-sensitive Streptococcus pneumoniae. Cytological analysis of the pericardial fluid was consistent with infection. The patient improved after 2 weeks of targeted antibiotic therapy and underwent the first cycle of chemotherapy. He was discharged with an early scheduled pulmonology appointment. Conclusions: Although the most common causes of pericardial effusion in lung cancer are malignant, non-malignant etiologies should also be considered. This patient had an infectious pericardial effusion most probably due to a pericardial-mediastinal mass fistula caused by radiotherapy. This was a diagnostic challenge, both in the emergency room as well in the inpatient setting. LEARNING POINTS: Small cell lung cancer is a fast-growing cancer that exhibits aggressive behavior.In patients with lung cancer, malignant pericardial effusions are more common than non-malignant ones.Purulent pericardial effusions, especially those due to lung cancer, are rare in developed countries with very few reports in the literature.

4.
Ann Surg Oncol ; 31(2): 847-859, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37934383

RESUMO

BACKGROUND: Preoperative exercise training is recommended for improvement of clinical outcomes after lung cancer (LC) surgery. However, its effectiveness in preventing postoperative decline in quality of life (QoL) remains unknown. This study investigated the effect of preoperative home-based exercise training (PHET) on QoL after LC surgery. METHODS: Patients awaiting LC resection were randomized to PHET or a control group (CG). The PHET program combined aerobic and resistance exercise, with weekly telephone supervision. Primary outcome was QoL-assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) at baseline, before surgery, and 1 month after surgery. The secondary outcomes were hospital length of stay and physical performance. The main analysis included a factorial repeated-measures analysis of variance. Additionally, the proportion of patients experiencing clinical deterioration from baseline to post-surgery was assessed. RESULTS: The study included 41 patients (68.1 ± 9.3 years; 68.3% male) in the intention-to-treat analysis (20 PHET patients, 21 CG patients). A significant group × time interaction was observed for global QoL (p = 0.004). Between-group differences in global QoL were statistically and clinically significant before surgery (mean difference [MD], 13.5 points; 95% confidence interval [CI], 2.4-24.6; p = 0.019) and after surgery (MD, 12.4 points; 95% CI, 1.3-23.4; p = 0.029), favoring PHET. Clinical deterioration of global QoL was reported by 71.4% of the CG patients compared with 30 % of the PHET patients (p = 0.003). Between-group differences in favor of PHET were found in pain and appetite loss as well as in physical, emotional and role functions after surgery (p < 0.05). Compared with CG, PHET was superior in improving preoperative five-times sit-to-stand and postoperative exercise capacity (p < 0.05). No between-group differences in other secondary outcomes were observed. CONCLUSION: The study showed that PHET can effectively prevent the decline in QoL after LC surgery.


Assuntos
Deterioração Clínica , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Qualidade de Vida , Neoplasias Pulmonares/cirurgia , Exercício Pré-Operatório , Exercício Físico
5.
Hansen. int ; 49: 39344, 2024.
Artigo em Português | LILACS, Sec. Est. Saúde SP, HANSEN, CONASS, Hanseníase, SESSP-ILSLPROD, Sec. Est. Saúde SP, SESSP-ILSLACERVO, Sec. Est. Saúde SP | ID: biblio-1553924

RESUMO

Introdução: a hanseníase é uma do-ença infecciosa crônica causada pelo Mycobacterium leprae (M. leprae), um para-sita intracelular obrigatório. Assim, a resis-tência do hospedeiro a esse patógeno depen-de da imunidade celular. O uso de modelos experimentais tem permitido o estudo da hanseníase do ponto de vista imunológico, microbiológico e terapêutico, entretanto, as diferenças na progressão da infecção entre os modelos mais empregados (camundongos imunocompetentes, BALB/c, e camundongos congenitamente atímicos, nude) são pouco estudadas. Objetivo: comparar a evolução da infecção pelo M. leprae em camundongos BALB/c e nude quanto à multi-plicação bacilar e avaliação do perfil inflamatório sistêmico pela quantificação sérica de citocinas e óxido nítrico (NO). Métodos: os camundongos foram inoculados com M. leprae nos coxins plantares e avaliados aos 3, 5 e 8 meses após a infecção. Resultados: camundongos nude apresentaram multiplicação bacilar progressiva nos coxins plantares. Em camundongos BALB/c, o número de bacilos foi maior aos 5 meses. Em relação à quantificação de citocinas, nos camundongos BALB/c houve aumento de IL-2 e IL-17A e diminuição de IL-6 e NO aos 8 meses de inoculação. Nos camundongos nude, verificou-se o aumento do TNF aos 8 meses de inoculação e manutenção dos níveis de NO. Conclusão: os resultados encontrados sugerem que em camundongos BALB/c ocorre a ativação de uma resposta imune capaz de controlar a multiplicação do M. leprae, em contrapartida em camundongos nude a infecção é progressiva a despeito de altos níveis de TNF. (AU)


Introduction: leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae), an obligate intracellular parasite. Thus, host resistance to this pathogen depends on cellular immunity. The use of experimental models has made it possible to study leprosy from an immunological, microbiological, and therapeutic point of view. However, the differences in the progression of the infection between the most used models (immunocompetent mice, BALB/c, and congenitally athymic mice, nude) have been little studied. Objective: to compare the evolution of M. leprae infection in BALB/c and nude mice in terms of bacillary multiplication and evaluation of the systemic inflammatory profile by quantifying serum cytokines and nitric oxide (NO). Methods: the mice were inoculated with M. leprae in the footpads and evaluated at 3, 5, and 8 months after infection. Results: nude mice showed progressive bacillary multiplication in the footpads. In BALB/c mice, the number of bacilli was higher at 5 months. In terms of cytokine quantification, BALB/c mice showed an increase in IL-2 and IL-17A and a decrease in IL-6 and NO at 8 months of inoculation. In the nude mice, there was an increase in TNF at 8 months of inoculation and maintenance of NO levels. Conclusion: the results suggest that BALB/c mice activate an immune response capable of controlling the multiplication of M. leprae, whereas in nude mice the infection is progressive despite high levels of TNF. (AU)


Assuntos
Animais , Camundongos , Hanseníase/imunologia , Imunidade Celular , Animais de Laboratório
6.
Saúde Soc ; 33(1): e220584pt, 2024. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1536866

RESUMO

Resumo Centrando-se no impacto que a comunicação de risco emitida pelas organizações de saúde pública tem na mudança dos comportamentos da sociedade, esta investigação pretende analisar as mensagens-chave que a Organização Mundial de Saúde (OMS) definiu para promover o programa de vacinação contra a covid-19. Para cumprir este objetivo, enveredou-se por uma metodologia de estudo qualitativa, que privilegiou o uso da análise do conteúdo publicado nas páginas de Facebook e de Instagram da OMS, no período de 1 de abril a 31 de agosto de 2021. No total, foram analisadas 62 publicações. Os resultados mostraram que a OMS utilizou quatro eixo de comunicação para promover a importância da vacinação na sociedade: garantir a credibilidade e a transparência da informação transmitida; certificar a segurança e a eficácia da vacina; apelar ao sentido de responsabilidade coletiva; e associar a vacina à solução para pôr fim à pandemia. As conclusões do estudo mostram que, embora a equidade no acesso à vacina ainda seja uma realidade em construção, os quase 70% da população mundial vacinada sugerem que as mensagens enviadas pela OMS no contexto de comunicação de risco podem ter contribuído para a construção de uma imagem positiva do programa de vacinação.


Abstract Focusing on the impact that risk communication issued by public health organizations brings to changing societal behaviors, this research aimed to analyze the key messages that the World Health Organization (WHO) has defined to promote the COVID-19 vaccination program. In order to achieve this goal, a qualitative study methodology was used to analyze the content published on the WHO's Facebook and Instagram pages from April 1 to August 31, 2021. In total, 62 publications were analyzed. The results showed that the WHO used four key communication messages to promote the importance of vaccination in society: ensuring the credibility and transparency of the information transmitted; certifying the safety and efficacy of the vaccine; appealing to a sense of collective responsibility; and associating the vaccine with the solution to end the pandemic were the chosen communication axes. The conclusions of this study show that, although fair access to the vaccine is still a reality in the making, the fact that almost 70% of the world's population has been vaccinated suggests that the messages sent by the WHO in the context of risk communication may have contributed to building a positive image of the vaccination program.

7.
Healthcare (Basel) ; 11(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37830726

RESUMO

Cancer patients may experience significant distress. The "Emotion Thermometers" (ETs) are a short visual analogue scale used to screen patients for psychosocial risk. This study aimed to assess emotional distress in a large sample of cancer patients attending psychological services at an non-governmental organization (NGO), and to explore factors that may contribute to it. The ETs were answered by 899 cancer patients. They were, on average, 59.9 years old, the majority were female, had breast cancer, were under treatment or were disease-free survivors, and reported high levels of emotional distress, above the cut-off (≥5). A Generalized Linear Model was used to measure the association between the level of distress, age, gender, disease phase and 33 items of the problem list. Four items-sadness, depression, sleep and breathing-were found to be significantly related to a higher level of distress. Additionally, women and patients who were in the palliative phase also had significantly higher levels of distress. The results confirm the need for early emotional screening in cancer patients, as well as attending to the characteristics of each patient. Additionally, they highlight the utility of the ETs for the clinical practice, allowing to optimize the referral to specialized psychosocial services.

8.
J Cancer Policy ; 38: 100437, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37625468

RESUMO

BACKGROUND: This study aims to provide an academic medical overview of the framework and key outcomes of two mammography quality certification programs in Brazil. METHODS: These programs assess radiation dose and phantom image quality in mammography units through a postal system. Each unit that passes this initial assessment is required to submit a sample of copies of five complete examinations. The quality of the patient images and reports is then reviewed by radiologists and medical physicist experts. Additionally, the number of mammography units and mammography coverage in the target population, were assessed. RESULTS: During the study period, 1007 units applied to the certification programs, and 934 (92.8%) successfully passed the assessment of radiation dose and phantom image quality. Out of these, 556 (59.5%) also passed the review of clinical image quality and reports, earning certification. The main issues related to mammogram and report quality were associated with the performance of radiographers (in terms of positioning) and radiologists (in terms of interpretation). On average, there are more than two mammography units/10,000 women in the target group. The screening mammography coverage in this group is 26.3% for women relying exclusively on the public healthcare and 58.1% for women with private healthcare plans. CONCLUSION: This study demonstrates the suitability of the framework adopted by national mammography quality certification programs in a middle-income country. These programs are carried out by relatively small workforce and at reasonable costs, utilizing postal resources to cover the large number of existing mammographic units and the vast distances within the country. POLICY STATEMENT: All mammography services in Brazil must adhere to the quality requirements for examinations and reference values for radiation dose to women established by the Ministry of Health. This ensures standardized conditions for early detection of breast cancer and minimizes the risk associated with x-rays.


Assuntos
Neoplasias da Mama , Mamografia , Feminino , Humanos , Brasil , Neoplasias da Mama/diagnóstico , Detecção Precoce de Câncer , Mamografia/métodos , Recursos Humanos
9.
J Clin Med ; 12(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37109307

RESUMO

BACKGROUND: Clinical guidelines recommend prehabilitation with exercise training to optimize recovery after lung cancer surgery. However, the lack of access to facility-based exercise programs is a major barrier to routine participation. This study aimed to assess the feasibility of a home-based exercise intervention before lung cancer resection. METHODS: We conducted a prospective, two-site feasibility study, including patients scheduled for lung cancer surgery. Exercise prescription involved aerobic and resistance training with telephone-based supervision. The primary endpoint was overall feasibility (recruitment rate, retention rate, intervention adherence and acceptability). Secondary endpoints included safety and effects on health-related quality of life (HRQOL) and physical performance, evaluated at baseline, after the exercise intervention and 4-5 weeks after surgery. RESULTS: Over three months, 15 patients were eligible, and all agreed to participate (recruitment rate: 100%). A total of 14 patients completed the exercise intervention, and 12 patients were evaluated postoperatively (retention rate: 80%). The median length of the exercise intervention was 3 weeks. Patients performed an aerobic and resistance training volume higher than prescribed (median adherence rates of 104% and 111%, respectively). A total of nine adverse events occurred during the intervention (Grade 1, n = 8; Grade 2, n = 1), the most common being shoulder pain. After the exercise intervention, significant improvements were observed in the HRQOL summary score (mean difference, 2.9; 95% confidence interval [CI], from 0.9 to 4.8; p = 0.049) and the five-times sit-to-stand test score (median difference, -1.5; 95% CI, from -2.1 to -0.9; p = 0.001). After surgery, no significant effects on HRQOL and physical performance were observed. CONCLUSION: A short-term preoperative home-based exercise intervention is feasible before lung cancer resection and may enhance accessibility to prehabilitation. Clinical effectiveness should be investigated in future studies.

10.
J Cell Biol ; 222(5)2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37017932

RESUMO

Enduring chromosome segregation errors represent potential threats to genomic stability due to eventual chromosome copy number alterations (aneuploidy) and formation of micronuclei-key intermediates of a rapid mutational process known as chromothripsis that is found in cancer and congenital disorders. The spindle assembly checkpoint (SAC) has been viewed as the sole surveillance mechanism that prevents chromosome segregation errors during mitosis and meiosis. However, different types of chromosome segregation errors stemming from incorrect kinetochore-microtubule attachments satisfy the SAC and are more frequent than previously anticipated. Remarkably, recent works have unveiled that most of these errors are corrected during anaphase and only rarely result in aneuploidy or formation of micronuclei. Here, we discuss recent progress in our understanding of the origin and fate of chromosome segregation errors that satisfy the SAC and shed light on the surveillance, correction, and clearance mechanisms that prevent their transmission, to preserve genomic stability.


Assuntos
Aneuploidia , Segregação de Cromossomos , Instabilidade Genômica , Humanos , Anáfase , Cinetocoros , Microtúbulos , Mitose , Fuso Acromático
11.
Pediatr Blood Cancer ; 70(7): e30352, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37057832

RESUMO

Local therapies are increasingly used for ocular preservation in retinoblastoma. In middle-income countries, these techniques pose specific challenges mostly related to more advanced disease at diagnosis. The Grupo de America Latina de Oncología Pediátrica (GALOP) developed a consensus document for the management of conservative therapy for retinoblastoma. Intra-arterial chemotherapy (OAC) is the preferred therapy, except for those with less advanced disease or age younger than 6 months. OAC allowed for a reduction in the use of external beam radiotherapy in our setting. Intravitreal chemotherapy is the preferred treatment for vitreous seeding. Enucleation is the treatment of choice for eyes with advanced disease.


Assuntos
Neoplasias da Retina , Retinoblastoma , Humanos , Lactente , Retinoblastoma/tratamento farmacológico , Neoplasias da Retina/tratamento farmacológico , Tratamento Conservador , Consenso , América do Sul , Estudos Retrospectivos
12.
Mar Drugs ; 21(3)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36976221

RESUMO

Sargassum is one of the largest and most diverse genus of brown seaweeds, comprising of around 400 taxonomically accepted species. Many species of this genus have long been a part of human culture with applications as food, feed, and remedies in folk medicine. Apart from their high nutritional value, these seaweeds are also a well-known reservoir of natural antioxidant compounds of great interest, including polyphenols, carotenoids, meroterpenoids, phytosterols, and several others. Such compounds provide a valuable contribution to innovation that can translate, for instance, into the development of new ingredients for preventing product deterioration, particularly in food products, cosmetics or biostimulants to boost crops production and tolerance to abiotic stress. This manuscript revises the chemical composition of Sargassum seaweeds, highlighting their antioxidant secondary metabolites, their mechanism of action, and multiple applications in fields, including agriculture, food, and health.


Assuntos
Sargassum , Alga Marinha , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Sargassum/química , Alga Marinha/química , Polifenóis/farmacologia , Carotenoides
13.
Microbiol Spectr ; : e0512422, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36971589

RESUMO

Vulvovaginal candidiasis (VVC) is one of the most prevalent vaginal infectious diseases. The increasing incidence of drug-resistant Candida strains and the limited therapeutic options make the discovery of effective alternative therapies fundamental. Essential oils (EOs) have been suggested as a promising alternative, and interestingly, vapor-phase essential oils (VP-EOs) present more advantages than their direct application. Thus, this study aims to evaluate the effect of oregano VP-EO (VP-OEO) on biofilms of antifungal-resistant vaginal isolates of Candida species (Candida albicans and Candida glabrata) and determine its mode of action. CFU, membrane integrity, and metabolic activity were evaluated. Furthermore, a reconstituted vaginal epithelium was used to mimic vaginal conditions and evaluate the effect of VP-OEO on Candida species infection, analyzed by DNA quantification, microscopy, and lactate dehydrogenase activity. The results revealed high VP-OEO antifungal activity. There was a significant reduction (>4 log CFU) in Candida species biofilms. Furthermore, the results show that the mechanisms of action of VP-OEO are related to membrane integrity and metabolic activity. The epithelium model confirms the effectiveness of VP-OEO. This study suggests that VP-EO can be considered a first approach for the development of an alternative form of VVC treatment. IMPORTANCE This work presents a new approach to the application of essential oils, exposure to the vapor phase, which can be considered a first approach for the development of a complementary or alternative form of vulvovaginal candidiasis (VVC) treatment. VVC is a significant infection caused by Candida species and remains a common disease that affects millions of women every year. The great difficulty in treating VVC and the extremely limited effective therapeutic options make the development of alternative treatments crucial. In this scope, this study aims to contribute to the development of effective, inexpensive, and nontoxic strategies for the prevention and treatment of this infectious disease, based on natural products. Moreover, this new approach has several advantages for women, such as lower costs, easy access, an easier mode of application, avoidance of skin contact, and, therefore, fewer negative impacts on women's health.

14.
Arq. neuropsiquiatr ; 81(3): 296-307, Mar. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1439437

RESUMO

Abstract Plasma exchange (PLEX) is a therapeutic apheresis modality in which the plasma is separated from inflammatory factors such as circulating autoreactive immunoglobulins, the complement system, and cytokines, and its therapeutic effect is based on the removal of these mediators of pathological processes. Plasma exchange is well established for various neurological disorders, and it is applied successfully in central nervous system inflammatory demyelinating diseases (CNS-IDD). It mainly modulates the humoral immune system; thus, it has a greater theoretical effect in diseases with prominent humoral mechanisms, such as neuromyelitis optica (NMO). However, it also has a proven therapeutic effect in multiple sclerosis (MS) attacks. Several studies have suggested that patients with severe attacks of CNS-IDD have poor response to steroid therapy but show clinical improvement after the PLEX treatment. Currently, PLEX is generally established only as a rescue therapy for steroid unresponsive relapses. However, there are still research gaps in the literature regarding plasma volume, number of sessions, and how early the apheresis treatment needs to started. Thus, in the present article, we summarize the clinical studies and meta-analyses, especially about MS and NMO, outlining clinical data regarding the experience with therapeutic PLEX in severe attacks of CNS-IDD, the clinical improvement rates, the prognostic factors of a favorable response, and highlighting the likely role of the early apheresis treatment. Further, we have gathered this evidence and suggested a protocol for the treatment of CNS-IDD with PLEX in the routine clinical practice.


Resumo Plasmaférese (PLEX) é um procedimento em que o plasma é separado de fatores inflamatórios como imunoglobulinas autorreativas circulantes, sistema complemento e citocinas, e seu efeito terapêutico se baseia na remoção desses mediadores de processos patológicos. A PLEX está bem estabelecida no tratamento de diversos distúrbios neurológicos, e é utilizada com sucesso em surtos de doenças desmielinizantes inflamatórias do sistema nervoso central (CNS-IDD). A PLEX modula principalmente o sistema imunológico humoral; assim, tem efeito teórico maior em doenças com mecanismos patológicos humorais proeminentes, como a neuromielite óptica (NMO). No entanto tem também efeito terapêutico comprovado em surtos de esclerose múltipla (EM). Estudos sugerem que a corticoterapia é pouco eficaz em pacientes com surtos graves de CNS-IDD, e que estes apresentam melhora clínica após o tratamento com PLEX. Atualmente, a PLEX está geralmente estabelecida apenas como terapia de resgate para surtos não responsivos a corticosteroides. No entanto, há lacunas na literatura sobre a quantidade de troca de volume plasmático, o número de sessões, e o tempo de início da aférese terapêutica. Dessa forma, resumimos neste artigo estudos clínicos e metanálises, especialmente sobre EM e NMO, e delineamos os dados clínicos sobre a experiência com o uso de PLEX em surtos graves de CNS-IDD, as taxas de melhora clínica, os fatores prognósticos para uma resposta favorável, e destacamos o provável papel do tratamento precoce nestes casos. Em um segundo momento, reunimos essas evidências em uma sugestão de protocolo de tratamento de CNS-IDD com PLEX na prática clínica rotineira.

15.
Cell Rep ; 42(3): 112148, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36827184

RESUMO

Unscheduled R loops can be a source of genome instability, a hallmark of cancer cells. Although targeted proteomic approaches and cellular analysis of specific mutants have uncovered factors potentially involved in R-loop homeostasis, we report a more open screening of factors whose depletion causes R loops based on the ability of activation-induced cytidine deaminase (AID) to target R loops. Immunofluorescence analysis of γH2AX caused by small interfering RNAs (siRNAs) covering 3,205 protein-coding genes identifies 59 potential candidates, from which 13 are analyzed further and show a significant increase of R loops. Such candidates are enriched in factors involved in chromatin, transcription, and RNA biogenesis and other processes. A more focused study shows that the DDX47 helicase is an R-loop resolvase, whereas the MeCP2 methyl-CpG-binding protein uncovers a link between DNA methylation and R loops. Thus, our results suggest that a plethora of gene dysfunctions can alter cell physiology via affecting R-loop homeostasis by different mechanisms.


Assuntos
Proteômica , Estruturas R-Loop , Humanos , Cromatina , Cromossomos/metabolismo , DNA Helicases/metabolismo , Instabilidade Genômica
16.
Clin Ophthalmol ; 17: 487-496, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36755890

RESUMO

Purpose: We aim to report about effectiveness and safety in the context of our centers' setting in the management of retinoblastoma with intra-arterial chemotherapy (IAC) in a 5-year retrospective analysis of the Portuguese population. Patients and Methods: Retrospective analysis of consecutive cases of retinoblastoma selected to initiate IAC between 2015 and 2020, at the Portuguese National Reference Center. All included patients underwent complete ophthalmological evaluation under anesthesia with fundus photography. Diagnosis and classification of retinoblastoma was made according to the International Classification of Intraocular Retinoblastoma (ICRB). The patients were further divided into two groups: Group I for primary IAC and Group II for secondary IAC. Tumor recurrence or relapses, systemic metastasis and deaths were documented. Main efficacy outcome included ocular salvage and recurrence-free survival rates estimated using the Kaplan-Meier method. Results: Twenty-eight eyes (19 eyes included in Group I and 9 eyes included in Group II) were eligible and a total of 130 IAC procedures were performed, with a median number of sessions of 4 (range 1-8) for each treated eye, during a median follow-up of 21 months (range 4-64). Of the included eyes, 22 (78.6%) were preserved. An overall survival of 100% was achieved. Considering the preserved eyes, the overall median decimal visual acuity achieved at the last visit was 0.15 (range 0.02-0.8). Three patients had permanent adverse events related to IAC (cataract, vitreous hemorrhage and choroidal ischemia). Considering the survival analysis of recurrence, the mean survival without recurrence was 84.2% for Group I and 66.7% for Group II, and the mean survival without enucleation was 78.6% (no events in Group II). Conclusion: IAC has been shown to be an effective and safe treatment for children with intraocular retinoblastoma. This study demonstrates that IAC is effective even in moderate sample sizes, when a multidisciplinary approach is available.

17.
Cardiol Young ; 33(8): 1440-1441, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36514995

RESUMO

Vena caval filters remain as a useful tool in patients with deep vein thrombosis and contraindications to anticoagulation. Although they are rarely used in paediatric patients, they have been shown to be safe and effective when used in the inferior vena cava.In this case report, we describe the off-label use of a retrievable vena caval filter in the superior vena cava in an adolescent with acute lymphoblastic leukaemia with extensive thrombosis of the right upper neck veins as a means to reduce the risk of pulmonary embolism.


Assuntos
Embolia Pulmonar , Filtros de Veia Cava , Trombose Venosa , Humanos , Adolescente , Criança , Filtros de Veia Cava/efeitos adversos , Veia Cava Superior , Uso Off-Label , Embolia Pulmonar/complicações , Trombose Venosa/complicações
19.
Antibiotics (Basel) ; 11(11)2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36358132

RESUMO

This study investigated the anti-caries and anti-inflammatory effects of mouthwash formulations containing Punica granatum (pomegranate) peel extract (PPE), sodium-trimetaphosphate, and low concentrations of fluoride. PPE was characterized using high-performance liquid chromatography (ellagic acid and punicalagin). Total phenolics were quantified among formulations, and their stability was analyzed for 28 days. The formulation effects were evaluated as follows: (1) inorganic component concentration and reduced demineralization on bovine enamel blocks subjected to pH cycling; (2) anti-biofilm effect on dual-biofilms of Streptococcus mutans ATCC 25175 and Candida albicans ATCC 10231 treated for 1 and 10 min, respectively; and (3) cytotoxicity and production of inflammatory mediators (interleukin-6 and tumor necrosis factor-alpha). The formulation containing 3% PPE, 0.3% sodium-trimetaphosphate, and 225 ppm of fluoride resulted in a 34.5% surface hardness loss; a 13% (treated for 1 min) and 36% (treated for 10 min) biofilm reduction in S. mutans; a 26% (1 min) and 36% (10 min) biofilm reduction in C. albicans; absence of cytotoxicity; and anti-inflammatory activity confirmed by decreased interleukin-6 production in mouse macrophages. Thus, our results provide a promising prospect for the development of an alcohol-free commercial dental product with the health benefits of P. granatum that have been recognized for a millennium.

20.
Pediatr Pulmonol ; 57(12): 3178-3179, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35999184

RESUMO

Negative pressure pulmonary edema (NPPE) in the context of anesthesia is a rare condition, although pediatric patients are at higher risk. This case stands out for the severe respiratory clinic that quickly developed in a child with a cancer history whose radiological and clinical presentation suggested multiple differential diagnoses, including tumor recurrence with metastasis or pulmonary tuberculosis. NPPE is a well-described, but a probably underrecognized clinical syndrome, that occurs after intense inspiratory effort against an obstructed airway. In clinical practice, when unexplained pulmonary edema takes place, NPPE should be considered in the differential diagnosis. NPPE usually has a favorable prognosis but pediatricians, radiologists, and anesthesiologists should be aware of this complication.


Assuntos
Obstrução das Vias Respiratórias , Anestésicos , Neoplasias , Edema Pulmonar , Humanos , Criança , Edema Pulmonar/diagnóstico por imagem , Edema Pulmonar/etiologia , Neoplasias/complicações , Obstrução das Vias Respiratórias/diagnóstico
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