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1.
Eur J Appl Physiol ; 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38613678

RESUMO

BACKGROUND: Walking/run promotes greater post-exercise hypotension (PEH) than resistance exercise (RE) which can be associated nitric oxide production. Then, we investigated if adding walking between RE increases PEH. METHODS: Thirteen hypertensive women (48 ± 1.9 years; 26.8 ± 0.3 kg/m2) performed five experimental sessions: 1-traditional RE with passive interval (PIBS); 2-RE with active interval between sets (AIBS); 3-RE with active interval between exercises (AIEX); 4-aerobic exercise (AE); 5-no exercise. Blood pressure was measured before and immediately after exercise and every 10 min of a 60-min post-exercise recovery period. Plasma nitrite (NO) and malondialdehyde (MDA) were also measured. RESULTS: AIBS, AIEX, and AE sessions promoted systolic PEH (12 ± 1.53; 16 ± 2.13; 18 ± 1.34 mmHg, respectively) and diastolic PEH (8 ± 1.38; 8 ± 0.79; 8 ± 0.58 mmHg). In AIBS, AIEX and AE sessions, significant PEH was noted at 10 or 20 min; in PIBS, PEH was significant only at 40 min. In the PIBS session, NO did not change, but presented higher values after AIBS, AIEX and AE sessions. MDA showed no changes between sessions. CONCLUSIONS: Passive or active intervals in resistance exercise promote PEH in hypertensive women. Active intervals shorten the PEH onset time as additional benefit.

2.
Exp Parasitol ; 252: 108587, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37454922

RESUMO

Fasciola hepatica, the liver trematode, infects ruminants and causes economic loss. Because parasites are developing resistance to commercial drugs, the negative effects of parasitism are increasing. In this study, we aimed to evaluate the efficacy of cumin (Cuminum cyminum) essential oil against F. hepatica eggs and adults. The eggs were incubated with eight concentrations of the essential oil (0.031125-4.15 mg/mL), and viable eggs were counted after 14 days and classified as embryonated or non-embryonated. Adult flukes were incubated in Roswell Park Memorial Institute medium to ensure their viability and then incubated in essential oil. They were observed for 24 h after treatment. The adults were assessed with the two lowest effective oil concentrations used in the ovicidal test. Three controls were used for both tests: nitroxynil, a negative control, and Tween®80. After incubation in oil, the adult specimens were processed for histological analysis and stained with hematoxylin-eosin. In addition, the oil was tested for cytotoxicity using Madin-Darby bovine kidney cells to assess any possible effect on them. The oil was effective in ovicidal and adulticidal inhibition of the trematode, with statistically significant results. All concentrations assessed in the ovicidal test were 100% effective. The adult test was effective within 15 h and inactivated all the specimens at the highest concentration evaluated (0.06225 mg/mL). Histological analysis showed that cumin essential oil resulted in marked areas of vacuolization. The spines showed no structural changes but were surrounded by microvesicles. These findings indicated that cumin oil could be a potential compound in the control of fasciolosis.


Assuntos
Anti-Helmínticos , Cuminum , Fasciola hepatica , Fasciolíase , Óleos Voláteis , Bovinos , Animais , Fasciolíase/tratamento farmacológico , Fasciolíase/veterinária , Fasciolíase/parasitologia , Cuminum/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Óleos Voláteis/química
3.
J Obstet Gynaecol Res ; 48(11): 2872-2878, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35908174

RESUMO

AIM: To determine the incidence of cervical cancer in women referred through the 2-week-wait pathway for postcoital bleeding and abnormal appearance of the cervix. METHODS: A retrospective cohort study was conducted of women with postcoital bleeding, or abnormal appearance of the cervix referred to colposcopy clinics through the 2-week-wait pathway for suspected cervical cancer at Cambridge University Hospitals in the United Kingdom over 5 years. Women were identified from a departmental database. Clinical and demographic data were collected. Categorical data was analyzed with chi-squared or Fisher's exact tests and predictive values were calculated. RESULTS: Of the 604 women referred, 1.16% were diagnosed with cervical cancer. None of the women who were up-to-date with cervical screening were diagnosed with cervical cancer, while 6.25% of women out-of-date with cervical screening or outside the screening age group were diagnosed with cervical cancer (p < 0.001). The positive predictive value for diagnosing cervical cancer was 1.70% for postcoital bleeding (95% confidence interval [CI] 0.64-3.7) and 0.31% for abnormal appearance of the cervix (95% CI 0.0008-1.7). CONCLUSIONS: The incidence of cervical cancer in women referred through the 2-week-wait pathway for postcoital bleeding and abnormal appearance of the cervix is low. These referrals have considerable implications for both patients and clinicians, and have a low predictive value for diagnosing cervical cancer. In light of emerging evidence and changing practices, referral guidelines should be reviewed based on up-to-date data and current practices.


Assuntos
Displasia do Colo do Útero , Neoplasias do Colo do Útero , Gravidez , Feminino , Humanos , Neoplasias do Colo do Útero/diagnóstico , Colo do Útero , Colposcopia , Detecção Precoce de Câncer , Incidência , Estudos Retrospectivos , Encaminhamento e Consulta , Hemorragia , Reino Unido , Displasia do Colo do Útero/diagnóstico
4.
An Acad Bras Cienc ; 94(suppl 4): e20220134, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36477824

RESUMO

In sports, training needs to be done according to various training patterns to optimize performance. However, this has been a major challenge to athletes due to the COVID-19 pandemic, therefore describing the impacts of lockdown caused by the COVID-19 pandemic on the athlete's training routine is necessary. 52 Brazilian athletes (Age: 31.5±10.3 years; Body Mass Index: 23.9±3.5 kg/m²), Olympic and Paralympic sports practitioners (professional and recreational) answered an online questionnaire [frequency, duration and intensity (subjective perception of effort) of training sessions], before and during lockdown (July to November/2020). The weekly training frequency (sessions/week) reduced by 48.1% (n=25) and was significantly higher among those who performed more than eight sessions before the pandemic (75% of them, p<0.000). The duration of the sessions (hours/day) decreased by 55.8% (n=29) and was significantly higher in athletes who performed training lasting more than one hour/day [75.9% of them (n=22)] and 24.1% (n= 7) performed training for more than two hours/day (p=0.132). The subjective perception of effort significantly decreased by 56%, from 8.4±1.2 to 5.5±1.7 (p=0.001). Because of the lockdown, athletes have suffered a reduction in the frequency, volume and intensity of their training sessions, but only in those with higher pre-pandemic training loads.


Assuntos
COVID-19 , Esportes , Humanos , Adulto Jovem , Adulto , COVID-19/epidemiologia , Pandemias , Controle de Doenças Transmissíveis , Brasil/epidemiologia
5.
Ann Hematol ; 100(1): 63-78, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32556451

RESUMO

Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases, with a variable probability of transformation into acute leukemia, which is, in the vast majority of cases, of myeloid lineage. Nevertheless, rare cases of acute lymphoblastic leukemia in patients with previously diagnosed MDS have been reported. We describe a series of 3 cases of MDS/CMML marked with evolution to acute lymphoblastic leukemia (ALL) and provide a comprehensive review of the 49 cases documented in the literature so far. These sporadic events have only been published as single-case reports or small series to date. Such atypical cases emphasize the possibility of major phenotypic switches arising at the leukemic stem cell (LSC) and/or early progenitor levels, as a consequence of epigenetic and genomic events driving these changes in the bone marrow niche.


Assuntos
Progressão da Doença , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
6.
Trop Anim Health Prod ; 53(5): 475, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34553290

RESUMO

The emergence of tick-borne diseases has been reported as a serious problem in public health worldwide and many aspects of its epidemiology and effects on the health of its hosts are unclear. We aimed to perform an epidemiological study of tick-borne zoonotic Rickettsia, Borrelia, and Anaplasmataceae in horses from Midwestern Brazil. We also evaluated whether Borrelia spp. and Anaplasmataceae may be associated with hematological disorders in the sampled animals. Blood and serum samples as well as ticks were collected from 262 horses. Serum samples were used to perform serological tests, and hematological analyses were made using whole blood. Furthermore, DNA extracted from whole blood and ticks was used for molecular tests. Campo Grande is enzootic for tick-borne studied bacteria, since we found an overall exposure of 59.9% of the sampled horses, 28.7% of them presented co-exposure. Seropositivity rates of 20.6% for Borrelia spp., 25.6% for Rickettsia spp., and 31.6% for Anaplasmataceae were found in the sampled horses. Considering both molecular and serological tests for Borrelia spp., the infection rate was 48.0% (126/262). None of the tested horses showed molecular positivity for Anaplasma phagocytophilum. The horses sampled displayed 7.2% of parasitism by ixodid ticks in single and coinfestations. We did not find DNA of any studied bacteria in the sampled ticks. Positive horses for Borrelia spp. and Anaplasmataceae agents displayed leukopenia, monocytopenia, and lymphopenia. Together, our results suggest that horses may play a role as sentinel host for zoonotic bacteria and Borrelia spp. and Anaplasmataceae agents can impair the health of horses.


Assuntos
Borrelia , Doenças dos Cavalos , Ixodes , Rickettsia , Doenças Transmitidas por Carrapatos , Animais , Brasil/epidemiologia , Doenças dos Cavalos/epidemiologia , Cavalos , Doenças Transmitidas por Carrapatos/epidemiologia , Doenças Transmitidas por Carrapatos/veterinária
7.
Br J Cancer ; 123(5): 793-802, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32555365

RESUMO

BACKGROUND: PTEN loss is a putative driver in histotypes of ovarian cancer (high-grade serous (HGSOC), endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous (LGSOC)). We aimed to characterise PTEN expression as a biomarker in epithelial ovarian cancer in a large population-based study. METHODS: Tumours from 5400 patients from a multicentre observational, prospective cohort study of the Ovarian Tumour Tissue Analysis Consortium were used to evaluate associations between immunohistochemical PTEN patterns and overall survival time, age, stage, grade, residual tumour, CD8+ tumour-infiltrating lymphocytes (TIL) counts, expression of oestrogen receptor (ER), progesterone receptor (PR) and androgen receptor (AR) by means of Cox proportional hazard models and generalised Cochran-Mantel-Haenszel tests. RESULTS: Downregulation of cytoplasmic PTEN expression was most frequent in ENOC (most frequently in younger patients; p value = 0.0001) and CCOC and was associated with longer overall survival in HGSOC (hazard ratio: 0.78, 95% CI: 0.65-0.94, p value = 0.022). PTEN expression was associated with ER, PR and AR expression (p values: 0.0008, 0.062 and 0.0002, respectively) in HGSOC and with lower CD8 counts in CCOC (p value < 0.0001). Heterogeneous expression of PTEN was more prevalent in advanced HGSOC (p value = 0.019) and associated with higher CD8 counts (p value = 0.0016). CONCLUSIONS: PTEN loss is a frequent driver in ovarian carcinoma associating distinctly with expression of hormonal receptors and CD8+ TIL counts in HGSOC and CCOC histotypes.


Assuntos
PTEN Fosfo-Hidrolase/biossíntese , Adenocarcinoma de Células Claras/enzimologia , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Fatores Etários , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Epitelial do Ovário/enzimologia , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/mortalidade , Carcinoma Epitelial do Ovário/patologia , Estudos de Coortes , Regulação para Baixo , Feminino , Técnicas de Inativação de Genes , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , PTEN Fosfo-Hidrolase/deficiência , PTEN Fosfo-Hidrolase/genética , Estudos Prospectivos , Receptores Androgênicos/biossíntese , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/biossíntese , Análise Serial de Tecidos , Proteínas Supressoras de Tumor/biossíntese , Proteínas Supressoras de Tumor/deficiência
8.
J Neurooncol ; 146(1): 181-193, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31836957

RESUMO

BACKGROUND: Evidence pointing to a synergistic effect of stereotactic radiosurgery (SRS) with concurrent immunotherapy or targeted therapy in patients with melanoma brain metastases (BM) is increasing. We aimed to analyze the effect on overall survival (OS) of immune checkpoint inhibitors (ICI) or BRAF/MEK inhibitors initiated during the 9 weeks before or after SRS. We also evaluated the prognostic value of patients' and disease characteristics as predictors of OS in patients treated with SRS. METHODS: We identified patients with BM from cutaneous or unknown primary origin melanoma treated with SRS between 2011 and 2018. RESULTS: We included 84 patients. The median OS was 12 months (95% CI 9-20 months). The median follow-up was 30 months (95% CI 28-49). Twenty-eight patients with newly diagnosed BM initiated anti-PD-1 +/-CTLA-4 therapy (n = 18), ipilimumab monotherapy (n = 10) or BRAF+/- MEK inhibitors (n = 11), during the 9 weeks before or after SRS. Patients who received anti-PD-1 +/-CTLA-4 mAb showed an improved survival in comparison to ipilimumab monotherapy (OS 24 vs. 7.5 months; HR 0.32, 95% 0.12-0.83, p = 0.02) and BRAF +/-MEK inhibitors (OS 24 vs. 7 months, respectively; HR 0.11, 95% 0.04-0.34, p = 0.0001). This benefit remained significant when compared to the subgroup of patients treated with dual BRAF/MEK inhibition (BMi) (n = 5). In a multivariate Cox regression analysis an age > 65, synchronous BM, > 2 metastatic sites, > 4 BM, and an ECOG > 1 were correlated with poorer prognosis. A treatment with anti-PD-1+/-CTLA-4 mAbs within 9 weeks of SRS was associated with better outcomes. The presence of serum lactate dehydrogenase (LDH) levels ≥ 2xULN at BM diagnosis was associated with lower OS (HR 1.60, 95% CI 1.03-2.50; p = 0.04). CONCLUSIONS: The concurrent administration of anti-PD-1+/-CTLA-4 mAbs with SRS was associated with improved survival in melanoma patients with newly diagnosed BM. In addition to CNS tumor burden, the extension of systemic disease retains its prognostic value in patients treated with SRS. Elevated serum LDH levels are predictors of poor outcome in these patients.


Assuntos
Neoplasias Encefálicas/terapia , Imunoterapia/mortalidade , Ipilimumab/uso terapêutico , Melanoma/terapia , Terapia de Alvo Molecular/mortalidade , Inibidores de Proteínas Quinases/uso terapêutico , Radiocirurgia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Masculino , Melanoma/imunologia , Melanoma/metabolismo , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
9.
Lancet Oncol ; 20(1): e54-e64, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30614479

RESUMO

Immune checkpoint inhibitors are reshaping the prognosis of many cancer and are progressively becoming the standard of care in the treatment of many tumour types. Immunotherapy is bringing new hope to patients, but also a whole new spectrum of toxicities for healthcare practitioners to manage. Oncologists and specialists involved in the pluridisciplinary management of patients with cancer are increasingly confronted with the therapeutic challenge of treating patients with severe and refractory immune-related adverse events. In this Personal View, we summarise the therapeutic strategies that have been used to manage such toxicities resulting from immune checkpoint inhibitor treatment. On the basis of current knowledge about their pathogenesis, we discuss the use of new biological and non-biological immunosuppressive drugs to treat severe and steroid refractory immune-related adverse events. Depending on the immune infiltrate type that is predominant, we propose a treatment algorithm for personalised management that goes beyond typical corticosteroid use. We propose a so-called shut-off strategy that aims at inhibiting key inflammatory components involved in the pathophysiological processes of immune-related adverse events, and limits potential adverse effects of drug immunosuppression on tumour response. This approach develops on current guidelines and challenges the step-by-step increase approach to drug immunosuppression.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Imunoterapia/efeitos adversos , Algoritmos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/fisiopatologia , Humanos , Neoplasias/terapia , Medicina de Precisão
10.
Rev Med Suisse ; 12(519): 994-8, 2016 May 18.
Artigo em Francês | MEDLINE | ID: mdl-27424427

RESUMO

Renal cell carcinoma (RCC) is composed of several histopathological entities. There are more than 1,000 new cases in Switzerland every year, one third of which are diagnosed at an advanced stage. The development of chemotherapy had no impact on its overall prognosis. Since the mid-2000s, treatment of metastatic RCC was transformed by the arrival of targeted therapies. In the early 90s, high dose interleukine-2 (IL-2) allowed first cases of complete response, demonstrating the immunogenicity of RCC. More than twenty years after its first steps, immunotherapy progressed due to the recently approved nivolumab (an anti-PD1 monoclonal antibody) in second line of treatment. This review outlines the progress that has been made in the understanding and treatment of this pathology.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Humanos , Imunoterapia/métodos , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Nivolumabe , Prognóstico , Suíça
11.
Rev Med Suisse ; 12(519): 989-93, 2016 May 18.
Artigo em Francês | MEDLINE | ID: mdl-27424426

RESUMO

Adoptive cell therapy consists in the use of T lymphocytes for therapeutic purposes. Up to now, of limited use in clinical practice for logistical reasons, technical progress and substantial level of evidence obtained in the last decade allow its arrival in universitary hospitals. We will principally discuss the administration of expanded tumor infiltrating T cells in the treatment of metastatic melanoma. This treatment modality exploits the natural specificity of these cells and aims to potentiate their effectiveness. This personalized immunotherapy detains a potential for expansion to many other advanced tumor types.


Assuntos
Imunoterapia Adotiva/métodos , Linfócitos do Interstício Tumoral/imunologia , Melanoma/terapia , Humanos , Melanoma/imunologia , Melanoma/patologia , Metástase Neoplásica , Medicina de Precisão , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia
12.
Rev Port Cir Cardiotorac Vasc ; 22(2): 97-100, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-27927002

RESUMO

OBJECTIVES: The authors' objective is to report their experience in the treatment of this rare and challenging condition. METHODS: Retrospective study including all patients diagnosed with Pancoast tumour submitted to surgery, between April 2006 and July 2015. Data concerning the patients submitted to resection surgery with curative intent and statistical analysis. RESULTS: The sample consists of nine patients, five of which underwent diagnostic thoracoscopy and the other four, resection surgery with curative intent. The mean age was 61,5 ± 13.5 years, with predominance of the male gender (n=3). The most common presenting symptom was omalgia irradiating to the ipsilateral arm (n=3). Three patients underwent induction chemoradiotherapy (CRT) with tumour downstaging and all patients were submitted to superior lobectomy with en bloc resection of the invaded structures. The surgical approaches chosen where Dartevelle (n=2) and Shawn-Paulson (n=2). A complete resection was achieved in all patients and no cases of major complications and perioperative mortality were registered. Only non-small cell lung carcinomas (NSCLC) were registered. Two mortality cases were documented before the five years follow-up. CONCLUSIONS: The results obtained are accordant with those registered on the literature. Portuguese data on this matter are scarce and the authors hope that the publication of this article will raise awareness and enhance knowledge regarding the management of Pancoast tumours.

13.
Int J Med Inform ; 182: 105306, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38065003

RESUMO

BACKGROUND: The British Gynaecological Cancer Society (BGCS) has highlighted the disparity of ovarian cancer outcomes in the UK compared to other European countries. Therefore, cancer quality assurance audits and subspecialty training are important in improving the UK standard of care for these patients. The current workforce crisis afflicting the NHS creates difficulty in dedicating teams of clinicians to these audits. We present a single institution study to evaluate if NLP-generated code can improve the efficiency of ovarian cancer and subspeciality reaccreditations audits. We used the chat bot Google Bard to write Visual Basic Applications algorithms that utilise Excel files from electronic health records. METHODS: Primary ovarian cancer data from 2019 to 2022 was retrospectively collected from the Cambridge University Hospital electronic health records. The surgical subspecialty reaccreditation audit analysed the 2022 surgical database. A modular coding approach with Google Bard was applied to generate audit algorithms. The time to complete these current audits was compared against the 2016 ovarian cancer and 2020 subspeciality reaccreditation audits. RESULTS: The previous ovarian cancer audit conducted in 2016 required 3 clinicians for the 135 cases and data collection required 1800 min. Data analysis was completed in 300 min. The current ovarian cancer audit allocated 2 clinicians to the 600 surgical cases. Data collection was completed in 3120 min, 3360 min for code development and 720 min for testing. The 2020 subspecialty reaccreditation audit was completed in 360 min. The 2022 subspecialty reaccreditation audit was completed in 1680 min, with 960 min for code development, 240 for debugging and 480 min for testing. CONCLUSION: We have demonstrated that NLP-generated code can significantly increase the efficiency of surgical quality assurance audits by eliminating the need for manual data analysis. With the current trajectory of NLP development, increasingly complex algorithms can be developed with minimal programming knowledge.


Assuntos
Processamento de Linguagem Natural , Neoplasias Ovarianas , Feminino , Humanos , Estudos Retrospectivos , Neoplasias Ovarianas/cirurgia , Coleta de Dados , Reino Unido , Auditoria Médica
14.
Cancer Res ; 84(6): 808-826, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38345497

RESUMO

Heterochromatin loss and genetic instability enhance cancer progression by favoring clonal diversity, yet uncontrolled replicative stress leads to mitotic catastrophe and inflammatory responses that promote immune rejection. KRAB domain-containing zinc finger proteins (KZFP) contribute to heterochromatin maintenance at transposable elements (TE). Here, we identified an association of upregulation of a cluster of primate-specific KZFPs with poor prognosis, increased copy-number alterations, and changes in the tumor microenvironment in diffuse large B-cell lymphoma (DLBCL). Depleting two of these KZFPs targeting evolutionarily recent TEs, ZNF587 and ZNF417, impaired the proliferation of cells derived from DLBCL and several other tumor types. ZNF587 and ZNF417 depletion led to heterochromatin redistribution, replicative stress, and cGAS-STING-mediated induction of an interferon/inflammatory response, which enhanced susceptibility to macrophage-mediated phagocytosis and increased surface expression of HLA-I, together with presentation of a neoimmunopeptidome. Thus, cancer cells can exploit KZFPs to dampen TE-originating surveillance mechanisms, which likely facilitates clonal expansion, diversification, and immune evasion. SIGNIFICANCE: Upregulation of a cluster of primate-specific KRAB zinc finger proteins in cancer cells prevents replicative stress and inflammation by regulating heterochromatin maintenance, which could facilitate the development of improved biomarkers and treatments.


Assuntos
Heterocromatina , Neoplasias , Animais , Heterocromatina/genética , Dedos de Zinco/genética , Elementos de DNA Transponíveis , Primatas/genética , Inflamação/genética , Neoplasias/genética
16.
Cureus ; 15(1): e33814, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36819325

RESUMO

Primary biliary cholangitis (PBC) is an autoimmune disease in which the intrahepatic bile ducts are destroyed. Its symptoms include chronic fatigue, pruritus, steatorrhea, and jaundice, with variable clinical course. We are introducing a case of a 65-year-old woman with anorexia, weight loss, asthenia, and pruritus. The imaging studies revealed dilatation of the intrahepatic and common bile ducts and adenopathies at the level of the hepatoduodenal ligament, histologically compatible with reactive lymphadenitis. After the exclusion of neoplasia, she was referred to Internal Medicine where positivity was obtained for anti-mitochondrial autoantibodies suggestive of PBC. After the initiation of therapy, there was a resolution of the clinical symptoms and the adenopathies were no longer detected in subsequent studies. The authors intend to highlight this case, especially due to the presence of adenopathies and constitutional symptoms where PBC should also be considered, as a differential diagnosis.

17.
Melanoma Manag ; 10(3): MMT66, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38229953

RESUMO

Vulvo-vaginal melanomas are one of the rarest gynecological oncology diseases with a poor survival compared with other malignancies. The 5-year survival varies from 13% to 32.3%. Vulvo-vaginal melanomas involving the upper 2/3rds of the vagina are usually treated with total pelvic exenteration (TPE). TPE surgery carries a 50% risk of major complications and also morbidity associated with double stomas. Central pelvic compartment resection is a novel organ-sparing surgical approach entailing radical total laparoscopic hysterectomy, bilateral salpingo-oophrectomy, laparoscopic vaginectomy and vulvectomy to reduce morbidity compared with TPE. Permanent suprapubic catheters are used if there is urethral involvement but require quality of life studies to assess their long-term outcomes.

18.
Materials (Basel) ; 16(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37444966

RESUMO

Polyamide 6 (PA6) thermoplastic composites have higher recyclability potential when compared to conventional thermoset composites. A disruptive liquid molding manufacturing technology named Thermoplastic Resin Transfer Molding (T-RTM) can be used for processing composites due to the low viscosity of the monomers and additives. In this process, polymerization, crystallization and shrinkage occur almost at the same time. If these phenomena are not controlled, they can compromise the reproducibility and homogeneity of the parts. This work studied the influence of packing pressure, as a process variable, throughout the filling and polymerization stages. To assess the process reproducibility and parts' homogeneity, physical, thermal and mechanical properties were analyzed in different areas of neat PA6 and composite parts. This study showed that a two-stage packing pressure can be successfully used to increase parts' homogeneity and process reproducibility. The use of 3.5 bar packing pressure during the polymerization stage resulted in mechanical properties with lower standard deviations, indicating a higher degree of homogeneity of the manufactured parts and higher process reproducibility. These results will be used for establishing the actual state of the technology and will be a base for future process optimization.

19.
Vet Parasitol ; 314: 109863, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36565643

RESUMO

Fasciolosis is one of the most important parasitic diseases in animal health, affecting mainly ruminants, causing economic and productivity losses. This study aimed to evaluate the in vitro ovicidal and adulticidal activity of essential oils (EOs) from Pelargonium graveolens (geranium) and Citrus aurantium (sour orange) on Fasciola hepatica. Performed Gas Chromatography of EOs P. graveolens and C. aurantium, with major compound, citronellol (31.37 %) and limonene (93.89 %), respectively. For the cytotoxicity assay, the sour orange EO showed to be promising when used in lower concentrations. For the ovicidal tests, the eggs were incubated with geranium EOs at concentrations from 4.5 to 0.03375 mg/mL and sour orange at concentrations from 4.25 to 0.031875 mg/mL, along with controls. The viable eggs were counted on the 14th day post-incubation. Adult forms of F. hepatica were incubated containing the EOs and observed for 24 h after treatment, as well as the control groups. Later the specimens were fixed for histological analysis. Geranium and sour orange EOs in trematode eggs at the concentrations tested were 100 % effective in inactivating hatching (p < 0.05) when compared to the untreated control. In the adulticidal test, the essential oil of P. graveolens at both concentrations tested (0.0675 and 0.03375) within 15 h, promoted the death of flukes. For C. aurantium, 18 h was enough to inactivate all specimens, up to a concentration of 0.06375. The histological analysis, observed the accumulation of liquid in the tegument in the specimens incubated in C. aurantium and P. graveolens, with vacuolization in the tegument and spines, preventing externalization. The results of the study present OEs with efficient ovicidal and adulticidal activity.


Assuntos
Citrus , Fasciola hepatica , Óleos Voláteis , Pelargonium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Pelargonium/química , Óvulo
20.
Vet Parasitol Reg Stud Reports ; 41: 100877, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37208084

RESUMO

The species in the genus Neotrichodectes (Phthiraptera: Ischnocera) infest carnivores. Neotrichodectes (Nasuicola) pallidus (Piaget, 1880), which has been primarily found parasitizing Procyonidae mammals, has been recorded in ring-tailed coatis (Nasua nasua) in the Brazilian states of Minas Gerais, Pernambuco, Santa Catarina, Rio Grande do Sul and Pernambuco. We report a new record of N. pallidus in coatis in the state of Mato Grosso do Sul, central-western Brazil, using morphological (Light and Scanning Electronic Microscopy) and molecular approaches (PCR, sequencing and phylogenetic analysis). Coatis were sampled in two peri-urban areas of Campo Grande city, Mato Grosso do Sul state, Brazil, between March 2018 and March 2019, as well as in November 2021. Lice were collected and examined under light and Scanning Electron Microscopy. DNA was also extracted from nymphs and adults and submitted to PCR assays based on the 18S rRNA and cox-1 genes for molecular characterization. One hundred and one coatis were sampled from 2018 to 2019 and 20 coatis in 2021 [when the intensity of infestation (II) was not accessed]. Twenty-six coatis (26/101-25.7%) were infested with at least one louse, with a total of 59 lice collected in 2018-2019. The II ranged from one to seven lice (mean 2.2 ± SD 1.7). The louse species was confirmed based on the following morphological characteristics: female gonapophyses rounded with the setae along anterior region but not in the medial margin; the male genitalia with a parameral arch not extending beyond the endometrial plate. The same ornamentation was observed on the abdomen of the females, males, and nymphs. The nymphs and the eggs were described in detail for the first time. The obtained 18S rRNA and cox1 sequences from N. pallidus clustered in a clade with other sequences of Ischnocera species. In the present study, a new record of the louse N. pallidus in central-western Brazil was provided, along with new insights into the morphological features of this species, with the first morphology contribution of nymphal and eggs stages.


Assuntos
Anoplura , Iscnóceros , Procyonidae , Animais , Masculino , Feminino , Filogenia , RNA Ribossômico 18S/genética , Mamíferos
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