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1.
Artigo em Inglês | MEDLINE | ID: mdl-38857454

RESUMO

OBJECTIVES: Precise literature recommendation and summarization are crucial for biomedical professionals. While the latest iteration of generative pretrained transformer (GPT) incorporates 2 distinct modes-real-time search and pretrained model utilization-it encounters challenges in dealing with these tasks. Specifically, the real-time search can pinpoint some relevant articles but occasionally provides fabricated papers, whereas the pretrained model excels in generating well-structured summaries but struggles to cite specific sources. In response, this study introduces RefAI, an innovative retrieval-augmented generative tool designed to synergize the strengths of large language models (LLMs) while overcoming their limitations. MATERIALS AND METHODS: RefAI utilized PubMed for systematic literature retrieval, employed a novel multivariable algorithm for article recommendation, and leveraged GPT-4 turbo for summarization. Ten queries under 2 prevalent topics ("cancer immunotherapy and target therapy" and "LLMs in medicine") were chosen as use cases and 3 established counterparts (ChatGPT-4, ScholarAI, and Gemini) as our baselines. The evaluation was conducted by 10 domain experts through standard statistical analyses for performance comparison. RESULTS: The overall performance of RefAI surpassed that of the baselines across 5 evaluated dimensions-relevance and quality for literature recommendation, accuracy, comprehensiveness, and reference integration for summarization, with the majority exhibiting statistically significant improvements (P-values <.05). DISCUSSION: RefAI demonstrated substantial improvements in literature recommendation and summarization over existing tools, addressing issues like fabricated papers, metadata inaccuracies, restricted recommendations, and poor reference integration. CONCLUSION: By augmenting LLM with external resources and a novel ranking algorithm, RefAI is uniquely capable of recommending high-quality literature and generating well-structured summaries, holding the potential to meet the critical needs of biomedical professionals in navigating and synthesizing vast amounts of scientific literature.

2.
J Am Heart Assoc ; 13(3): e029900, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38293921

RESUMO

BACKGROUND: The rapid evolution of artificial intelligence (AI) in conjunction with recent updates in dual antiplatelet therapy (DAPT) management guidelines emphasizes the necessity for innovative models to predict ischemic or bleeding events after drug-eluting stent implantation. Leveraging AI for dynamic prediction has the potential to revolutionize risk stratification and provide personalized decision support for DAPT management. METHODS AND RESULTS: We developed and validated a new AI-based pipeline using retrospective data of drug-eluting stent-treated patients, sourced from the Cerner Health Facts data set (n=98 236) and Optum's de-identified Clinformatics Data Mart Database (n=9978). The 36 months following drug-eluting stent implantation were designated as our primary forecasting interval, further segmented into 6 sequential prediction windows. We evaluated 5 distinct AI algorithms for their precision in predicting ischemic and bleeding risks. Model discriminative accuracy was assessed using the area under the receiver operating characteristic curve, among other metrics. The weighted light gradient boosting machine stood out as the preeminent model, thus earning its place as our AI-DAPT model. The AI-DAPT demonstrated peak accuracy in the 30 to 36 months window, charting an area under the receiver operating characteristic curve of 90% [95% CI, 88%-92%] for ischemia and 84% [95% CI, 82%-87%] for bleeding predictions. CONCLUSIONS: Our AI-DAPT excels in formulating iterative, refined dynamic predictions by assimilating ongoing updates from patients' clinical profiles, holding value as a novel smart clinical tool to facilitate optimal DAPT duration management with high accuracy and adaptability.


Assuntos
Doença da Artéria Coronariana , Stents Farmacológicos , Infarto do Miocárdio , Intervenção Coronária Percutânea , Humanos , Inibidores da Agregação Plaquetária/efeitos adversos , Infarto do Miocárdio/etiologia , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/cirurgia , Stents Farmacológicos/efeitos adversos , Inteligência Artificial , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Risco , Quimioterapia Combinada , Hemorragia/induzido quimicamente , Prognóstico , Intervenção Coronária Percutânea/efeitos adversos
3.
J Med Virol ; 95(12): e29248, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38108641

RESUMO

The infection caused by the hepatitis C virus (HCV) is a significant global health concern. The prevailing genotype of HCV in Egypt is 4a, commonly referred to as GT-4a. A significant proportion exceeding 50% of patients infected with HCV experience extrahepatic manifestations (EHMs), encompassing a diverse range of clinical presentations. These manifestations, including essential mixed cryoglobulinemia (MC), can serve as initial and solitary indicators of the disease. The complete understanding of the pathogenesis of EHM remains unclear, with autoimmune phenomena being recognized as the primary causative factor. In this study, we examined the predictive significance of T-cell subpopulations in relation to the occurrence and prognosis of cryoglobulinemia in HCV patients. A total of 450 CHC genotype four treatment naïve patients were enrolled in this analytic cross-sectional study after thorough clinical, laboratory, and radiological examinations. All patients underwent laboratory investigations, including testing for cryoglobulin antibodies and measurements of CD4 and CD8 levels; two groups were described according to their test results: Group 1 consists of patients who have tested positive for cryoglobulin antibodies and Group 2 consists of patients who have tested negative for cryoglobulin antibodies. The exclusion criteria encompassed individuals with HIV infection or chronic HBV infection. Additionally, pelvi-abdominal ultrasonography was performed. Our study included 450 treatment naïve CHC patients (59% male, mean age 50.8 years). The patients were categorized according to their cryoglobulin antibodys test results into two groups: group A, CHC patients with cryoglobulin antibodies (Abs) negative (364 patients), and group B, CHC patients with cryoglobulin Ab positive (86 patients). Group B demonstrated a higher average age, elevated international normalized ratio, more prolonged duration of HCV infection, lower albumin, higher alanine aminotransferase, higher aspartate aminotransferase, higher bilirubin, lower CD8, lower CD4, and lower CD4:CD8 ratio. In contrast, 27 out of 86 (31.40%) patients in group B had symptoms; 85.8% had purpura and arthralgia, 74.3% had paresthesias, 86.7% had weakness, and 12.2% had non-Hodgkin's lymphoma. The levels of CD4 and CD8 were found to be decreased in chronic HCV patients with MC. T-cell subpopulation serves as a reliable indicator for assessing the prevalence and prognosis of MC in individuals with genotype 4 chronic hepatitis C. However, additional research is needed to further understand the development and spread of various emerging infectious diseases. Nevertheless, it is noteworthy that a critical threshold may exist beyond which EHM reaches a point of no return.


Assuntos
Crioglobulinemia , Infecções por HIV , Hepatite C Crônica , Hepatite C , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Hepatite C Crônica/complicações , Hepatite C Crônica/epidemiologia , Crioglobulinemia/epidemiologia , Prevalência , Estudos Transversais , Crioglobulinas , Linfócitos T , Prognóstico , Hepacivirus/genética
4.
J Enzyme Inhib Med Chem ; 38(1): 2220570, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37341389

RESUMO

Novel 5-deazaflavins were designed as potential anticancer candidates. Compounds 4j, 4k, 5b, 5i, and 9f demonstrated high cytotoxicity against MCF-7 cell line with IC50 of 0.5-190nM. Compounds 8c and 9g showed preferential activity against Hela cells (IC50: 1.69 and 1.52 µM respectively). However, compound 5d showed notable potency against MCF-7 and Hela cell lines of 0.1 nM and 1.26 µM respectively. Kinase profiling for 4e showed the highest inhibition against a 20 kinase panel. Additionally, ADME prediction studies exhibited that compounds 4j, 5d, 5f, and 9f have drug-likeness criteria to be considered promising antitumor agents deserving of further investigation. SAR study showed that substitutions with 2-benzylidene hydra zino have a better fitting into PTK with enhanced antiproliferative potency. Noteworthy, the incorporation of hydrazino or ethanolamine moieties at position 2 along with small alkyl or phenyl at N-10, respectively revealed an extraordinary potency against MCF-7 cells with IC50 values in the nanomolar range.


Assuntos
Etanolamina , Etanolaminas , Humanos , Células HeLa , Flavinas
5.
Arch Pharm (Weinheim) ; 356(7): e2300035, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37080944

RESUMO

A series of seventeen 1,8-naphthyridine derivatives (5a-5q) conjugated at N1 to various substituted phenyl rings were designed and synthesized as potential topoisomerase II (Topo II) inhibitors. The antiproliferative activity of the target compounds against three cancer cell lines showed that compounds 5g and 5p had the highest antiproliferative activity. In addition, 5p and 5g displayed a high selectivity index (SI) for cancer cells when tested on WI38 normal cells, whereby compound 5p showed the highest SI. Furthermore, 5g and 5p induced cell cycle arrest at the S and G1/S phases, respectively, triggering apoptosis in HepG-2 cells. The in vitro Topo II inhibitory effect (plasmid-based) of both compounds revealed that 5p had better inhibition of Topo II. In addition, 5p displayed potent topoisomerase IIß inhibitory effect when compared to known topoisomerase inhibitors (doxorubicin and topotecan). Molecular docking proposed a unique binding pattern of 5p in the etoposide binding pocket of topoisomerase IIß, endorsing its potential role as a Topo II poison. Accordingly, 5p was chosen for radioiodination to study the degree of tumor localization following administration in solid tumor-bearing mice. The radioiodinated 5p showed a selective localization at the tumor site, which further confirmed the value of 5p as a lead 1,8-naphthyridine anticancer agent.


Assuntos
Antineoplásicos , Naftiridinas , Animais , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Simulação de Acoplamento Molecular , Naftiridinas/farmacologia , Linhagem Celular Tumoral , Radioisótopos do Iodo/farmacologia , Desenho de Fármacos , Antineoplásicos/química , Inibidores da Topoisomerase II , DNA Topoisomerases Tipo II/metabolismo , Apoptose
6.
Cureus ; 14(12): e32277, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36628003

RESUMO

The current meta-analysis aims to explore the effect of metformin use on vitamin B12 deficiency in patients with type 2 diabetes mellitus (T2DM) and the factors associated with it. This meta-analysis followed the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines. We searched PubMed and EMBASE from January 1, 2010, to October 31, 2022, to collect the studies that reported the effect of metformin on the deficiency of vitamin B12 in patients with T2DM and the factors associated with it. A total of 17 studies were included in the current meta-analysis. Among all the included studies, 13 were cross-sectional studies, 3 were retrospective cohorts, and one was a case-control study. The pooled rate of deficiency of vitamin B12 in patients receiving metformin (23.16%) was significantly higher compared to patients who were not on metformin (17.4%) (OR: 2.95, 95% CI: 2.18-4.00, p-value: 0.001). Factors significantly associated with vitamin B12 deficiency in patients with T2DM and receiving metformin include the duration of metformin use and a greater dose of metformin. In conclusion, our meta-analysis found that the prevalence of vitamin B12 deficiency is greater in patients receiving metformin compared to patients who did not receive metformin. Given the importance of vitamin B12 in nutrition, metformin-induced B12 decrease may be harmful to patients with T2DM. Supplemental vitamin B12 may be advantageous for those on metformin.

7.
Front Comput Neurosci ; 15: 650050, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33897397

RESUMO

Over the last few decades, electroencephalogram (EEG) has become one of the most vital tools used by physicians to diagnose several neurological disorders of the human brain and, in particular, to detect seizures. Because of its peculiar nature, the consequent impact of epileptic seizures on the quality of life of patients made the precise diagnosis of epilepsy extremely essential. Therefore, this article proposes a novel deep-learning approach for detecting seizures in pediatric patients based on the classification of raw multichannel EEG signal recordings that are minimally pre-processed. The new approach takes advantage of the automatic feature learning capabilities of a two-dimensional deep convolution autoencoder (2D-DCAE) linked to a neural network-based classifier to form a unified system that is trained in a supervised way to achieve the best classification accuracy between the ictal and interictal brain state signals. For testing and evaluating our approach, two models were designed and assessed using three different EEG data segment lengths and a 10-fold cross-validation scheme. Based on five evaluation metrics, the best performing model was a supervised deep convolutional autoencoder (SDCAE) model that uses a bidirectional long short-term memory (Bi-LSTM) - based classifier, and EEG segment length of 4 s. Using the public dataset collected from the Children's Hospital Boston (CHB) and the Massachusetts Institute of Technology (MIT), this model has obtained 98.79 ± 0.53% accuracy, 98.72 ± 0.77% sensitivity, 98.86 ± 0.53% specificity, 98.86 ± 0.53% precision, and an F1-score of 98.79 ± 0.53%, respectively. Based on these results, our new approach was able to present one of the most effective seizure detection methods compared to other existing state-of-the-art methods applied to the same dataset.

8.
Front Artif Intell ; 4: 636234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33748748

RESUMO

Soil moisture (SM) plays a significant role in determining the probability of flooding in a given area. Currently, SM is most commonly modeled using physically-based numerical hydrologic models. Modeling the natural processes that take place in the soil is difficult and requires assumptions. Besides, hydrologic model runtime is highly impacted by the extent and resolution of the study domain. In this study, we propose a data-driven modeling approach using Deep Learning (DL) models. There are different types of DL algorithms that serve different purposes. For example, the Convolutional Neural Network (CNN) algorithm is well suited for capturing and learning spatial patterns, while the Long Short-Term Memory (LSTM) algorithm is designed to utilize time-series information and to learn from past observations. A DL algorithm that combines the capabilities of CNN and LSTM called ConvLSTM was recently developed. In this study, we investigate the applicability of the ConvLSTM algorithm in predicting SM in a study area located in south Louisiana in the United States. This study reveals that ConvLSTM significantly outperformed CNN in predicting SM. We tested the performance of ConvLSTM based models by using a combination of different sets of predictors and different LSTM sequence lengths. The study results show that ConvLSTM models can predict SM with a mean areal Root Mean Squared Error (RMSE) of 2.5% and mean areal correlation coefficients of 0.9 for our study area. ConvLSTM models can also provide predictions between discrete SM observations, making them potentially useful for applications such as filling observational gaps between satellite overpasses.

9.
ACS Infect Dis ; 7(7): 1901-1922, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-33538576

RESUMO

Due to the limitations of existing medications, there is a critical need for new drugs to treat visceral leishmaniasis. Since arylimidamides and antifungal azoles both show oral activity in murine visceral leishmaniasis models, a molecular hybridization approach was employed where arylimidamide and azole groups were separated by phenoxyalkyl linkers in an attempt to capitalize on the favorable antileishmanial properties of both series. Among the target compounds synthesized, a greater antileishmanial potency against intracellular Leishmania donovani was observed as the linker length increased from two to eight carbons and when an imidazole ring was employed as the terminal group compared to a 1,2,4-triazole group. Compound 24c (N-(4-((8-(1H-imidazol-1-yl)octyl)oxy)-2-isopropoxyphenyl) picolinimidamide) displayed activity against L. donovani intracellular amastigotes with an IC50 value of 0.53 µM. When tested in a murine visceral leishmaniasis model, compound 24c at a dose of 75 mg/kg/day p.o. for five consecutive days resulted in a modest 33% decrease in liver parasitemia compared to the control group, indicating that further optimization of these molecules is needed. While potent hybrid compounds bearing an imidazole terminal group were also strong inhibitors of recombinant CYP51 from L. donovani, as assessed by a fluorescence-based assay, additional targets are likely to play an important role in the antileishmanial action of these compounds.


Assuntos
Antiprotozoários , Leishmania donovani , Leishmaniose Visceral , Preparações Farmacêuticas , Animais , Antiprotozoários/farmacologia , Azóis , Leishmania donovani/genética , Leishmaniose Visceral/tratamento farmacológico , Camundongos
10.
Int J Clin Pharm ; 43(3): 502-508, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33025448

RESUMO

Background Malaria is one of the main causes of death in Sudan with high prevalence among males, children under five-year and pregnant women. In 2016 near 13% of hospital admissions in Sudan were due to malaria. Community pharmacist dispensing of antimalarial drugs without prescription and malaria self-treatment may lead to the development of drugs resistance and delay disease control. Objective To assess the knowledge and practice of community pharmacists regarding malaria and its treatment. Setting Community pharmacies in Khartoum State, Sudan. Method A cross-sectional survey was carried using a structured pre-tested self-administered questionnaire for the pharmacists in charge of 320 randomly selected community pharmacies. Main outcome measures The community pharmacists'knowledge and practices regarding malaria and antimalarials dispensing. Results A total of 293 pharmacists participated in the study giving a response rate of 91.5%. About 92.2% of the respondents were from the age of 20-39 years and 63.8% had less than 5 years of experience. Community pharmacists showed inadequate knowledge regarding malaria and its treatment. In addition to that, they were dispensing antimalarials without prescriptions. The community pharmacists reported many barriers to their effective contribution in malaria prevention and treatment such as lack of knowledge, lack of time and lack of training. Conclusion Inadequate knowledge and irrational antimalarials dispensing practices were reported among the community pharmacists in Khartoum State. Although training was a significant predictor of pharmacists' knowledge regarding malaria and its treatment, health authorities were not providing regular training for the practicing pharmacists.


Assuntos
Serviços Comunitários de Farmácia , Malária , Adulto , Atitude do Pessoal de Saúde , Estudos Transversais , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Malária/tratamento farmacológico , Malária/epidemiologia , Malária/prevenção & controle , Masculino , Farmacêuticos , Gravidez , Sudão/epidemiologia , Inquéritos e Questionários , Adulto Jovem
11.
Am J Trop Med Hyg ; 104(2): 580-584, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-33245041

RESUMO

Hepatitis C virus (HCV) infection can affect the neurological system, and neuropathy is one of these manifestations. Hepatitis C virus infection is associated with diabetes mellitus (DM) type II, and diabetic patients are at higher risk of acquiring HCV infection. Sweat function has been proposed to assess early autonomic neuropathy. This study aimed to evaluate small fiber neuropathy in asymptomatic HCV-related cirrhotic patients with or without DM through sweat function assessment by Sudoscan test. Three groups were involved: 47 healthy controls, 48 HCV-related cirrhotic patients without DM (group 1), and 49 HCV-related cirrhotic patients with DM type II (group 2). All participants were subjected to liver panel tests, renal function tests, cell blood counts, HbA1c, and abdominal ultrasound. Sweat function was assessed in all patients and controls by measuring hand and feet electrochemical skin conductance (ESC, microSiemens [µS]) using Sudoscan. Peripheral neuropathy was detected in none of the controls, 39% of group 1 patients, and 62% of group 2 patients (P < 0.0001). The mean feet ESC (FESC) was 88.3 ± 6.8 µS in controls, 67.2 ± 19.2 µS in group 1, and 57.9 ± 19.4 µS in group 2 (P < 0.0001). A significant correlation was observed between FESC and bilirubin, albumin, creatinine, international normalized ratio, transaminases, and splenic size. Electrochemical skin conductance measurement is a valuable, noninvasive method for early detection of small fiber neuropathy in asymptomatic HCV-related cirrhosis, with or without DM.


Assuntos
Hepacivirus/patogenicidade , Hepatite C/complicações , Doenças do Sistema Nervoso Periférico/virologia , Idoso , Sistema Nervoso Autônomo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/virologia , Egito , Eletroquímica , Feminino , Pé/patologia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pele/patologia
12.
Braz J Cardiovasc Surg ; 35(4): 521-529, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32864933

RESUMO

OBJECTIVE: To detect the potential risk factors associated with early mortality in patients who received extensive surgical management, in the form of total arch replacement plus frozen elephant trunk and arch debranching (hybrid repair technique), for acute type A aortic dissection. METHODS: The clinical and surgical data of 452 surgically treated patients with acute type A aortic dissection at our center, between March 2010 and December 2016, have been retrieved. Uni and multivariate logistic regression analyses were carried out to detect the effect of various preoperative demographics and different perioperative variables on early mortality. RESULTS: Overall 30-day mortality occurred in 70 out of 452 patients (15.4%). The principal causes of death were multiple organ failure (n=38), cardiac failure (n=18), and severe pulmonary infection (n=10). Risk factors for early mortality were identified with multivariate analysis. Preoperatively, overweight (P<0.025), alcohol drinking (P<0.002), coronary artery disease (P<0.014), hemodynamic shock (P<0.006), and elevated white blood cells count (P<0.002) were associated with higher mortality rate. Postoperatively, prolonged operation time (P<0.008), stroke (P<0.0001), and acute renal dysfunction (P<0.0001) were highly associated with death. CONCLUSION: Considering the advantages of extensive surgical management for acute type A aortic dissection over the other less aggressive surgical approaches, it should be advised whenever indicated, provided that being carried out by experts in the field of adult aortic surgery in high-volume centers. The surgeon should be aware of the patient's preoperative comorbidities and other risk factors for early mortality, in particular, prolonged operation time.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Adulto , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
Rev. bras. cir. cardiovasc ; 35(4): 521-529, July-Aug. 2020. tab, graf
Artigo em Inglês | LILACS, Sec. Est. Saúde SP | ID: biblio-1137296

RESUMO

Abstract Objective: To detect the potential risk factors associated with early mortality in patients who received extensive surgical management, in the form of total arch replacement plus frozen elephant trunk and arch debranching (hybrid repair technique), for acute type A aortic dissection. Methods: The clinical and surgical data of 452 surgically treated patients with acute type A aortic dissection at our center, between March 2010 and December 2016, have been retrieved. Uni and multivariate logistic regression analyses were carried out to detect the effect of various preoperative demographics and different perioperative variables on early mortality. Results: Overall 30-day mortality occurred in 70 out of 452 patients (15.4%). The principal causes of death were multiple organ failure (n=38), cardiac failure (n=18), and severe pulmonary infection (n=10). Risk factors for early mortality were identified with multivariate analysis. Preoperatively, overweight (P<0.025), alcohol drinking (P<0.002), coronary artery disease (P<0.014), hemodynamic shock (P<0.006), and elevated white blood cells count (P<0.002) were associated with higher mortality rate. Postoperatively, prolonged operation time (P<0.008), stroke (P<0.0001), and acute renal dysfunction (P<0.0001) were highly associated with death. Conclusion: Considering the advantages of extensive surgical management for acute type A aortic dissection over the other less aggressive surgical approaches, it should be advised whenever indicated, provided that being carried out by experts in the field of adult aortic surgery in high-volume centers. The surgeon should be aware of the patient's preoperative comorbidities and other risk factors for early mortality, in particular, prolonged operation time.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Comorbidade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
14.
Bioorg Med Chem Lett ; 30(1): 126725, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732409

RESUMO

Cyanine compounds have previously shown excellent in vitro and promising in vivo antileishmanial efficacy, but the potential toxicity of these agents is a concern. A series of 22 analogs of thiazole orange ((Z)-1-methyl-4-((3-methylbenzo[d]thiazol-2(3H)-ylidene)methyl)quinolin-1-ium salt), a commercial cyanine dye with antileishmanial activity, were synthesized in an effort to increase the selectivity of such compounds while maintaining efficacy. Cyanines possessing substitutions on the quinolinium ring system displayed potency against Leishmania donovani axenic amastigotes that differed little from the parent compound (IC50 12-42 nM), while ring disjunction analogs were both less potent and less toxic. Changes in DNA melting temperature were modest when synthetic oligonucleotides were incubated with selected analogs (ΔTm ≤ 5 °C), with ring disjunction analogs showing the least effect on this parameter. Despite the high antileishmanial potency of the target compounds, their toxicity and relatively flat SAR suggests that further information regarding the target(s) of these molecules is needed to aid their development as antileishmanials.


Assuntos
Benzotiazóis/síntese química , Leishmaniose Visceral/metabolismo , Quinolinas/síntese química , Animais , Descoberta de Drogas
15.
Open Access Maced J Med Sci ; 6(11): 2180-2185, 2018 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-30559886

RESUMO

AIM: The study was conducted to evaluate the effect of combined low energy laser application and Micro-Osteoperforations versus the effect of the application of each technique separately on the rate of orthodontic tooth movement. PATIENTS AND METHODS: Three parallel groups (each group contained 10 patients) were performed; Group A: In which one side was controlled side, and the other side received micro-osteoperforations (MOPs), Group B: In which one side was controlled side, and the other side received low-level laser therapy (LLLT), Group C: In which one side was controlled side, and the other side received both MOPs and LLLT. RESULTS: Significant statistical differences were obvious in the rate of canine retraction between each intervention and the control sides as following; the MOPs increased the rate of canine retraction by 1.6 fold more than the control side, LLLT increased the rate of canine retraction by 1.3 fold than the control side, and combination of both techniques resulted in an increase in the rate of canine retraction by 1.8 fold more than the control side. CONCLUSION: Combination of MOPs and LLLT proved to be more efficient regarding increasing the rate of canine retraction than the application of each technique separately.

16.
J Pediatr Endocrinol Metab ; 31(3): 269-273, 2018 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-29537213

RESUMO

BACKGROUND: The objectives were to describe the frequency of clinical presentation at the onset of type 1 diabetes mellitus (T1DM) and to estimate the prevalence of T1DM among children and adolescents in the AL-Baha region, Saudi Arabia, aiming for early diagnosis of T1DM. METHODS: The clinical and laboratory data of 471 children and adolescents who presented with T1DM and received medical care at an AL-Baha diabetic center during the period from 2007 to 2016 were retrospectively analyzed based on the records. RESULTS: The prevalence of T1DM in the AL-Baha region was 355 per 100,000 population in participants aged from 0 to 19 years. T1DM was more common among girls than boys (57.5% vs. 42.5%, respectively; p=0.3), and the female/male ratio was 1.36 in favor of girls. Hyperglycemic symptoms were the most frequent symptoms at presentation [59.2% vs. 40.8% with diabetic ketoacidosis (DKA)], and 37% of them presented with loss of weight. Most of the ketoacidosis was mild to moderate (80.2%), while only 19.8% of children had the severe type and DKA was more common (55.2%) among females. The mean age at diagnosis of T1DM was 8.2±3.5 years for all patients, and 8.3±3.9 and 8.9±3.6 years for boys and girls, respectively (p=0.06). Hyperglycemic symptoms were more common in spring (15.9%). CONCLUSIONS: The prevalence of type 1 diabetes in the AL-Baha region was 355 per 100,000 population, which is one of the highest reported prevalences in this age group. Hyperglycemic symptoms were the most encountered symptoms at the onset of the presentation of T1DM and this may help in early detection of diabetic symptoms by patients and physicians to avoid the more severe types of presentation.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Cetoacidose Diabética/epidemiologia , Hiperglicemia/epidemiologia , Adolescente , Adulto , Idade de Início , Peso Corporal , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Cetoacidose Diabética/diagnóstico , Cetoacidose Diabética/etiologia , Feminino , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Lactente , Recém-Nascido , Masculino , Prevalência , Estudos Retrospectivos , Fatores de Risco , Arábia Saudita/epidemiologia , Adulto Jovem
17.
Arab J Urol ; 12(4): 299-303, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26019966

RESUMO

OBJECTIVE: To evaluate the outcome of using semi-rigid ureteroscopy with or without intracorporeal pneumatic lithotripsy vs. temporary ureteric JJ stenting in the management of obstructing ureteric calculi in pregnant women. PATIENTS AND METHODS: This prospective comparative study comprised 43 pregnant women with obstructing ureteric calculi. The diagnosis was based on the acute flank pain as the main symptom, microscopic haematuria, and unilateral hydronephrosis on abdominal ultrasonography (US). The patients were randomly divided into two groups; those in group 1 (22 patients) were treated by temporary ureteric JJ stenting until after delivery, and those in group 2 (21) were treated definitively by ureteroscopic stone extraction with intracorporeal pneumatic lithotripsy. Postoperative complications and the degree of patient satisfaction were reported. RESULTS: An obstructing ureteric stone was identified by US in 68% and 76% of groups 1 and 2, respectively. In group 1, nine patients had mid-ureteric stones and 13 had stones in the lower ureter. In group 2, seven patients had mid-ureteric stones, whilst the stones were in the distal ureter in 14. No perioperative foetal complications were detected in any group and all patients completed the full term of pregnancy. In group 1, four patients had a postoperative urinary tract infection (UTI), and the JJ stent was exchanged in seven. Two patients in group 2 had a postoperative UTI. CONCLUSIONS: Definitive ureteroscopy, even with intracorporeal pneumatic lithotripsy, is an effective and safe treatment for pregnant women with obstructing ureteric calculi. It has a better outcome and is more satisfactory for the patients than a temporary JJ stent.

18.
Artigo em Inglês | MEDLINE | ID: mdl-12386391

RESUMO

The assessment of students in community settings faces unique difficulties. Since students are usually posted in small groups in different community settings and since the learning (largely) takes place outside the classroom, assessing student performance becomes an intrinsically complex endeavor. In this article, the proposition is made and tested that peers may be used to accurately assess particular aspects of performance, in particular those which need extensive and close observation. Examples are: Effort displayed while working in a community, quality of the interaction with that community, display of leadership, and subject-matter contributions.The Faculty of Medicine of the University of Gezira, a community-based medical school, uses peer evaluation to assess these attributes of its students. Thirty four students divided into three groups participated in the present study. Goals of the study were to appraise the reliability, validity and acceptability of an instrument designed to measure these characteristics. Reliability was estimated using generalizability theory. A high generalizability coefficient (G) was found when all items were taken into account. In this case, G equaled 0.97. Its sub-scales each had also fairly high G-coefficients: Effort: 0.89, Subject-matter Contribution: 0.91, Community Interaction: 0.89, and Leadership: 0,88 respectively. The validity of the instrument was studied using confirmatory factor analysis. The results suggested that the proposed model of peer evaluation is reasonably valid. Finally, the instrument turned out to be quite acceptable to students.

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