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1.
Int J Mol Sci ; 25(9)2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38732252

RESUMO

Several studies have shown an inverse correlation between the likelihood of developing a neurodegenerative disorder and cancer. We previously reported that the levels of amyloid beta (Aß), at the center of Alzheimer's disease pathophysiology, are regulated by acetylcholinesterase (AChE) in non-small cell lung cancer (NSCLC). Here, we examined the effect of Aß or its fragments on the levels of ACh in A549 (p53 wild-type) and H1299 (p53-null) NSCLC cell media. ACh levels were reduced by cell treatment with Aß 1-42, Aß 1-40, Aß 1-28, and Aß 25-35. AChE and p53 activities increased upon A549 cell treatment with Aß, while knockdown of p53 in A549 cells increased ACh levels, decreased AChE activity, and diminished the Aß effects. Aß increased the ratio of phospho/total p38 MAPK and decreased the activity of PKC. Inhibiting p38 MAPK reduced the activity of p53 in A549 cells and increased ACh levels in the media of both cell lines, while opposite effects were found upon inhibiting PKC. ACh decreased the activity of p53 in A549 cells, decreased p38 MAPK activity, increased PKC activity, and diminished the effect of Aß on those activities. Moreover, the negative effect of Aß on cell viability was diminished by cell co-treatment with ACh.


Assuntos
Acetilcolina , Peptídeos beta-Amiloides , Carcinoma Pulmonar de Células não Pequenas , Sobrevivência Celular , Neoplasias Pulmonares , Proteína Quinase C , Proteína Supressora de Tumor p53 , Proteínas Quinases p38 Ativadas por Mitógeno , Humanos , Células A549 , Acetilcolina/metabolismo , Acetilcolina/farmacologia , Acetilcolinesterase/metabolismo , Peptídeos beta-Amiloides/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteína Quinase C/metabolismo , Proteína Supressora de Tumor p53/metabolismo
2.
J Pediatr Surg ; 59(7): 1342-1348, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38589272

RESUMO

BACKGROUND: Between 2005 and 2014, Ghana's Wilms tumor (WT) 2-year disease-free survival of 44% trailed behind that of high-income countries. This study aimed to uncover social determinants of health leading to preventable WT death in Ghana. METHODS: WT patient records (2014-2022) at Korle-Bu Teaching Hospital (KBTH; Ghana) were reviewed retrospectively. Demographics, clinical course, tumor characteristics, and survival were evaluated using t-tests, Pearson Chi-square, and multivariate Cox logistic regression. RESULTS: Of 127 patients identified, 65 were female. Median age was 44 months [IQR 25-66]. Forty-eight patients (38%) presented with distant metastasis (75% lung, 25% liver), which associated with hypoalbuminemia (p = 0.009), caregiver informal employment (p = 0.04), and larger tumors (p = 0.002). Despite neoadjuvant chemotherapy shrinking 84% of tumors, larger initial size associated with incomplete resection (p = 0.046). Of 110 nephrectomies, 31 patients had residual disease, negatively impacting survival (p = 2.7 × 10-5). Twenty-two patients (17%) abandoned treatment (45% before nephrectomy; 55% after nephrectomy), with seven patients ultimately lost to follow-up (LTFU). Decedents represented 43% of stage IV patients compared to 28% in other stages. Event-free survival (EFS) was 60% at 4 years with overall survival (OS) at 67%. CONCLUSIONS: Although Ghana's WT survival has improved, informal employment and distance from KBTH predisposed patients to delayed referral, greater tumor burden, hypoalbuminemia, and lower survival. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: II.


Assuntos
Neoplasias Renais , Nefrectomia , Tumor de Wilms , Humanos , Tumor de Wilms/terapia , Tumor de Wilms/mortalidade , Tumor de Wilms/patologia , Tumor de Wilms/cirurgia , Gana/epidemiologia , Feminino , Masculino , Estudos Retrospectivos , Pré-Escolar , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Carga Tumoral , Lactente , Criança , Intervalo Livre de Doença , Determinantes Sociais da Saúde , Terapia Neoadjuvante/estatística & dados numéricos
3.
BMC Pediatr ; 21(1): 88, 2021 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-33607970

RESUMO

BACKGROUND: Rotavirus is considered the main causal factor of severe gastroenteritis among infants and children globally. The association with severe rotavirus infection is mostly worse among the least developed countries, mainly due to inadequate access to medical care and poverty. This study was conducted to determine the seasonal effects in respect of diarrhea cases in children, the association between diarrhea cases and Rota2 vaccine in the Fanteakwa District of the Eastern Region of Ghana. METHODS: The study compares monthly diarrhea cases against children vaccinated with Rota2 extracted from DHIMS2 spanning May 2012 to December 2017 in Fanteakwa District. A univariate association between diarrhea cases and children vaccinated with Rota 2 was conducted using the R-software version 3.4.4 with the use of forecast, tseries and TSAPred. Pearson Correlation coefficient was also computed between monthly diarrhea cases and Rota 2 as well as lagged values of Rota 2 and Diarrhea cases. RESULTS: The study shows that February recorded the highest average number of diarrhea cases (172) over the period 2012 to 2017 with a standard deviation of 59. However, a one-way analysis of variance shows a significant difference amongst the monthly averages with an F-statistic of 0.042 and P-value of 0.064. It is observed that the correlations between each of the Rota2 doses and the lagged cases are positive, showing higher Rota2 doses a month ago ((Xt - 1),0.346 to 0.735), two months ago ((Xt - 2),0.383 to 0.746), three months ago ((Xt - 3), 0.330 to 0.737) and four months ago ((Xt - 4), 0.236 to 0.723) are associated with lower diarrhea cases. The results also show that an increase in the previous two month's Rota2 figures by 100 is associated with a significant decrease in the currently expected diarrhea cases by approximately 36. CONCLUSION: Seasonal variations exist in the occurrence of diarrhea in children, with January recording the highest number of diarrhea cases (172). There is a relationship between episodes of diarrhea in children and Rota2 (p-value = 0.064); thus, the more children are vaccinated with Rota2, the less diarrhea cases are recorded. Diarrhea cases in Fanteakwa district are generally low, except 2013 and 2016 where the cases are higher than the rest of the other years.


Assuntos
Infecções por Rotavirus , Vacinas contra Rotavirus , Rotavirus , Criança , Diarreia/epidemiologia , Diarreia/prevenção & controle , Gana/epidemiologia , Humanos , Lactente , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/prevenção & controle
4.
BMC Res Notes ; 11(1): 91, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29391046

RESUMO

OBJECTIVE: This study was conducted to determine the maternal and neonatal characteristics that influence very early neonatal mortality using 811 delivery records at the Eastern Regional Hospital of Ghana. RESULTS: The very early neonatal mortality rate was 9 per 1000 live births. Multi-parity reduced the odds of very early neonatal death by 30%. Mothers with a previous neonatal death had about 8 times the odds of having a very early neonatal death as compared to those without a history of neonatal death.


Assuntos
Mortalidade Infantil/tendências , Paridade/fisiologia , Morte Perinatal , Adolescente , Adulto , Feminino , Gana/epidemiologia , Hospitais , Humanos , Lactente , Recém-Nascido , Idade Materna , Gravidez , Estudos Retrospectivos , Fatores de Risco
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