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1.
Mol Divers ; 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38702561

RESUMO

The increasing spread of the Monkeypox virus (MPXV) presents a significant public health challenge, emphasising the urgent requirement for effective treatments. Our study focuses on the VP39 Methyltransferase enzyme of MPXV as a critical target for therapy. By utilising virtual screening, we investigated natural compounds with structural similarities to sinefungin, a broad-acting MTase inhibitor. From an initial set of 177 compounds, we identified three promising compounds-CNP0346326, CNP0343532, and CNP008361, whose binding scores were notably close to that of sinefungin. These candidates bonded strongly to the VP39 enzyme, hinting at a notable potential to impede the virus. Our rigorous computational assays, including re-docking, extended molecular dynamics simulations, and energetics analyses, validate the robustness of these interactions. The data paint a promising picture of these natural compounds as front-runners in the ongoing race to develop MPXV therapeutics and set the stage for subsequent empirical trials to refine these discoveries into actionable medical interventions.

2.
Cureus ; 16(3): e55883, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38595885

RESUMO

Niemann-Pick disease (NPD) encompasses a minimum of three lysosomal storage diseases, all of which are inherited in an autosomal recessive manner. Acid sphingomyelinase (ASM) deficiency is the cause of NPD types A and B. ASM is the enzyme that hydrolyzes the sphingolipid sphingomyelin. An 18-month-old patient with progressive painless abdominal distension with organomegaly and neurological deficits presented to our hospital. Brain imaging and laboratory findings did not show anything, but there was a millstone growth delay. The diagnosis of NPD type A was confirmed by a genetic examination, which revealed a twofold change on chromosome 11p15.4 in the region encoding the sphingomyelin phosphodiesterase-1 (SMPD1) gene. The patient was followed up with no specific treatment, and signs of respiratory infections were later reported.

3.
J Contemp Dent Pract ; 25(2): 148-155, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38514412

RESUMO

OBJECTIVE: This study aims to assess the perceptions and knowledge of undergraduate dental students about artificial intelligence (AI) in dental schools through a cross-sectional study. MATERIALS AND METHODS: This was a multicenter, cross-sectional study. Participant recruitment was achieved by sending an online questionnaire to the undergraduate students at the assigned universities. The questionnaire consisted of two parts. The first seven questions record general information about participants and their perceptions of AI. The remaining questions are about the knowledge of participants about the applications of AI. The data were analyzed using SPSS version 26. RESULTS: About 165 undergraduate students from 20 universities related to the dental sciences responded to the questionnaire. And 80.6% of participants found the use of AI in dentistry exciting. I have a basic knowledge of the working principles of AI. About 80.6% of participants believe that applications of AI should be part of undergraduate dental training. And 66.6% of students are aware of the opportunities and threats that AI can create. The results show that 75% of the students indicated that they got their information about AI through social media. Regarding the association of years of studies with AI applications used in periodontics, the knowledge about AI applications in "aggressive periodontics," "compromised teeth," and "success in rate of dental implant" was significantly higher in senior students than junior students (p < 0.05). Concerning applications of AI used in restorative dentistry and prosthodontics, only "computer color matching," "tooth surface losses," and "I do not know" showed statistical significance (p < 0.05) with the year of study of participants. Senior students show significantly better knowledge in "success in retreatment" and "working length determinant." CONCLUSION: Although undergraduates are enthusiastic about AI and aware of its threats and benefits, their knowledge is limited. In addition, undergraduate programs must exert more effort to prepare students for the era of AI. How to cite this article: Aldowah O, Almakrami A, Alghuwaynim Y, et al. Perceptions and Knowledge of Undergraduate Dental Students about Artificial Intelligence in Dental Schools: A Cross-sectional Study. J Contemp Dent Pract 2024;25(2):148-155.


Assuntos
Inteligência Artificial , Estudantes de Odontologia , Humanos , Estudos Transversais , Faculdades de Odontologia , Currículo
4.
Pathol Res Pract ; 256: 155225, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38442448

RESUMO

Diabetic cardiomyopathy, a multifaceted complication of diabetes mellitus, remains a major challenge in clinical management due to its intricate pathophysiology. Emerging evidence underscores the pivotal role of autophagy dysregulation in the progression of diabetic cardiomyopathy, providing a novel avenue for therapeutic intervention. Noncoding RNAs (ncRNAs), a diverse class of regulatory molecules, have recently emerged as promising candidates for targeted therapeutic strategies. The exploration of various classes of ncRNAs, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) reveal their intricate regulatory networks in modulating autophagy and influencing the pathophysiological processes associated with diabetic cardiomyopathy. The nuanced understanding of the molecular mechanisms underlying ncRNA-mediated autophagic regulation offers a rationale for the development of precise and effective therapeutic interventions. Harnessing the regulatory potential of ncRNAs presents a promising frontier for the development of targeted and personalized therapeutic strategies, aiming to ameliorate the burden of diabetic cardiomyopathy in affected individuals. As research in this field advances, the identification and validation of specific ncRNA targets hold immense potential for the translation of these findings into clinically viable interventions, ultimately improving outcomes for patients with diabetic cardiomyopathy. This review encapsulates the current understanding of the intricate interplay between autophagy and diabetic cardiomyopathy, with a focus on the potential of ncRNAs as therapeutic targets.


Assuntos
Diabetes Mellitus , Cardiomiopatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Humanos , Cardiomiopatias Diabéticas/genética , RNA não Traduzido/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Autofagia/genética
5.
Curr Oncol ; 31(1): 472-481, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38248117

RESUMO

OBJECTIVE: We investigated the potential relationship between endometriosis and risk of ovarian, endometrial, cervical, and breast cancers using the National Inpatient Sample (NIS) database. METHODS: We utilized the International Classification of Diseases (ICD-10) system to identify relevant codes from the NIS database (2016-2019). Univariate and multivariate regression analyses (adjusted for age, race, hospital region, hospital teaching status, income Zip score, smoking, alcohol use, and hormonal replacement therapy) were conducted to evaluate the association between endometriosis and gynecologic cancers and summarized as odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: In the examined dataset, there were 1164 and 225,323 gynecologic cancer patients with and without endometriosis, respectively. Univariate analysis showed endometriosis was significantly associated with a higher risk of ovarian (OR = 3.42, 95% CI: 3.05-3.84, p < 0.001) and endometrial (OR = 3.35, 95% CI: 2.97-3.79, p < 0.001) cancers. There was no significant association between endometriosis and cervical cancer (OR = 1.05, 95% CI: 0.85-1.28, p = 0.663). Interestingly, endometriosis was significantly associated with a low risk of breast cancer (OR = 0.12, 95% CI: 0.10-0.17, p < 0.001). Multivariate analysis after Bonferroni correction (p < 0.006) showed that endometriosis was significantly associated with a high risk of ovarian (adjusted OR = 3.34, 95% CI: 2.97-3.75, p < 0.001) and endometrial (adjusted OR = 3.61, 95% CI: 3.12-4.08, p < 0.001) cancers. Conversely, there was no significant association between endometriosis and cervical cancer (OR = 0.80, 95% CI: 0.65-0.99, p = 0.036). CONCLUSIONS: Patients with endometriosis exhibited unique gynecologic cancer risk profiles, with higher risks for ovarian and endometrial cancers, and no significant risk for cervical cancer. The observed connection between endometriosis and a reduced risk of breast cancer remains a perplexing phenomenon, which cannot be put into context to date.


Assuntos
Neoplasias da Mama , Endometriose , Neoplasias Ovarianas , Neoplasias do Colo do Útero , Feminino , Humanos , Pacientes Internados , Projetos de Pesquisa
6.
Cureus ; 15(8): e43432, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37706148

RESUMO

Branchial cleft cysts are birth defects that happen when the first through fourth pharyngeal clefts do not close properly and most of these cysts develop from the second cleft. Second branchial cleft cysts are almost always in the neck, so it is rare for them to present in the nasopharynx. We report an extremely rare case of a branchial cleft cyst that is located in an unusual site in the nasopharynx in a 36-year-old male with no prior medical history. Computed tomography scan findings showed non-enhancing thickening of the right side mucosal-pharyngeal space, obliterating the fossa of Rosenmuller with no invasion or erosion. The patient was admitted for nasopharyngeal mass excision, and the mass was sent for histopathology. When a cystic lesion is noted in the lateral nasopharynx, branchial cleft cysts should be on the list of possible diagnoses. Surgery is primarily the treatment. The marsupialization approach is a simple way to treat nasopharyngeal branchial cleft cysts as it is safe and has limited complications.

7.
Cureus ; 15(8): e43136, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37577274

RESUMO

Background The use of traditional medicine (TM) in children is widespread, particularly in developing countries. Parents often rely on TM to treat their children's illnesses or maintain their health. However, the safety and efficacy of TM are often unclear, and there is a need to assess parents' knowledge, attitudes, and practices toward its use. Methods This is a community-based cross-sectional study conducted in Bisha, Saudi Arabia, with a sample size of 555. The study used a modified questionnaire to collect data. The data were collected from March to June 2023. This study involved both descriptive and inferential statistics.  Results The study included 555 participants, most of whom were female, Saudi nationals, and married and had a bachelor's degree. More than half of the participants reported using TM, and most believed that it had fewer side effects and could be taken with allopathic medicines. However, many participants did not believe that TM could prevent or cure all diseases or that it was always safe. The median knowledge score was 4.0, with higher scores associated with older age and higher educational level. Most participants had a positive attitude toward TM, with higher attitude scores associated with younger age, male gender, lower educational level, and healthcare-related occupation. The median practice score was 31.0, with higher scores associated with younger age, male gender, illiteracy, and healthcare-related occupation. Overall, the study highlights the importance of understanding the patterns of use, knowledge, attitudes, and practices of TM in the population, particularly among different demographic groups. Conclusions This study highlights the need for better regulation and supervision of TM outlets to ensure the safety and efficacy of the products. It also emphasizes the importance of consulting healthcare professionals before using TM on children. The findings suggest that healthcare providers should be knowledgeable about TM and provide guidance to parents on its appropriate use.

8.
Medicina (Kaunas) ; 59(8)2023 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-37629766

RESUMO

Background and Objectives: Cardiovascular disease (CVD) is a major contributor to the high mortality rate among individuals with ovarian cancer. Nevertheless, there is limited understanding regarding the specific patient attributes that might impact the risk of CVD in this group. Materials and Methods: A retrospective cohort study was performed using the SEER database to analyze primary ovarian cancer cases from 2000 to 2019. Multivariable logistic regression analysis was employed to identify patient characteristics linked to cardiovascular mortality. Results: The cohort included 41,930 cases of patients who were alive, 54,829 cases of cancer-related deaths, 3003 cases of cardiovascular-related deaths, and 10,238 cases with other causes of death. Poorly differentiated cancer cells and distant metastasis were associated with a higher risk of cardiovascular mortality. Logistic regression analysis identified age, year of diagnosis, race, laterality, and staging as significant risk factors for cardiovascular cause of death. The risk of cardiovascular cause of death was lower in patients aged 31-60 and higher in those aged over 60 years old, and the risk also increased with a later year of diagnosis. Patients who were not white were at a higher risk of cardiovascular cause of death. Additionally, bilateral ovarian cancer and distant staging disease were linked to elevated risks of cardiovascular cause of death. Conclusion: Cardiovascular mortality is a significant concern in ovarian cancer patients, and several patient characteristics are associated with an increased risk. Our study suggests that targeted interventions to improve cardiovascular health in high-risk patients, such as those with comorbidities or an advanced stage at diagnosis, may improve survival in this population.


Assuntos
Doenças Cardiovasculares , Neoplasias Ovarianas , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Neoplasias Ovarianas/complicações , Doenças Cardiovasculares/complicações , Bases de Dados Factuais
9.
J Surg Case Rep ; 2023(5): rjad286, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37251246

RESUMO

The association between colorectal cancer and primary hyperparathyroidism has been reported as case reports in the literature. There are few data regarding the molecular explanation of such coexistence. Here we report a case with synchronous pathologies of primary hyperparathyroidism and colorectal cancer. Furthermore, the patient has a positive family history of the same two pathologies in one of his first-degree relatives. We reviewed the literature to clarify and explain the relationship between these two diseases. We aimed to shed light on the coexistence of such conditions and to clarify if there is a relation between them or if it is just a coincidence.

10.
Cureus ; 15(1): e33839, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36819406

RESUMO

Introduction Burn injuries are among the most catastrophic public health issues because of the severe physical, functional, and psychological effects. Numerous studies have revealed that both developed and developing societies lack understanding about first aid for burns. This research sought to review and appraise perception, awareness, and practices of burn first aid among non-healthcare providers in Jeddah, Saudi Arabia, and whether they need an effective program. To the best of our knowledge, this is likely the first research conducted in Jeddah. Methodology We conducted a cross-sectional study in Jeddah, Saudi Arabia using a self-administered online questionnaire among non-healthcare providers in July 2022. The questionnaire was made up of 29 questions divided into two sections: demographics and first aid for burns. The Unit of Biomedical Ethics Research Committee at the Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia approved this study. Results This study included 575 participants. Males comprised 54.8% (315) and females 45.2% (260) of all respondents. A total of 443 respondents (77%) held a university diploma. All respondents had a mean burn knowledge score of 6.35±1.43 out of eight. Traditional medication was used on the burn by 484 people (84.2%). Antibiotic use in burn injuries was poorly understood as 453 (78.8%) of study participants agreed that antibiotics are beneficial in the case of burns, which is incorrect. Conclusion The level of first-aid practices for burn patients among non-healthcare workers was insufficient, and the use of traditional medicines and antibiotics in burn patients was excessive. The findings of this study should be carefully considered by various healthcare organizations.

11.
Cureus ; 15(12): e50530, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38226113

RESUMO

BACKGROUND: A widespread and serious eye condition is a refractive error (RE). Globally, uncorrected refractive defects affect numerous individuals, with some who are blind. Numerous studies in Saudi Arabia have been conducted to assess reflective error. However, there is a lack of knowledge regarding RE among school-age children in Bisha province, southwest Saudi Arabia. This study aimed to determine the prevalence and types of RE among school-age children in Bisha, Saudi Arabia. METHODS: A cross-sectional study involved 360 schoolchildren from primary schools was carried out between December 2022 and November 2023 in Bisha. A validated questionnaire form was used to collect sociodemographic information and clinical data (history of the ocular problem, visual acuity test findings, and the refractor machine's result). RESULT: A total of 360 schoolchildren aged from seven to 14 years, with a mean of 10.1 years (standard deviation (SD)=2.05). The prevalence of hyperopia was 21% in the right eye and 23% in the left eye. In addition, the prevalence of myopia was 20% in the right eye and 22.5% in the left eye. A significant association between visual acuity and myopia (p=0.001). By contrast, there was no significant correlation between hyperopia and visual acuity (p=0.412). CONCLUSION: The current study summarized the prevalence of REs among school-age children in Bisha, Saudi Arabia. The study population included nearly half of those with at least some degree of RE. These results highlight the need for prompt and careful screening programs to detect and treat refractive disorders across this age range.

12.
J Med Chem ; 65(20): 14104-14120, 2022 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-36260129

RESUMO

The influenza A virus (IAV) is a highly contagious virus that causes pandemics and seasonal epidemics, which are major public health issues. Current anti-influenza therapeutics are limited partly due to the continuous emergence of drug-resistant IAV strains; thus, there is an unmet need to develop novel anti-influenza therapies. Here, we present a novel imidazo[1,2-a]pyrimidine scaffold that targets group 2 IAV entry. We have explored three different regions of the lead compound, and we have developed a series of small molecules that have nanomolar activity against oseltamivir-sensitive and -resistant forms of group 2 IAVs. These small molecules target hemagglutinin (HA), which mediates the viral entry process. Mapping a known small-molecule-binding cavity of the HA structure with resistant mutants suggests that these molecules bind to that cavity and block HA-mediated membrane fusion.


Assuntos
Vírus da Influenza A , Influenza Humana , Humanos , Vírus da Influenza A/metabolismo , Oseltamivir , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Hemaglutininas , Influenza Humana/tratamento farmacológico , Relação Estrutura-Atividade , Pirimidinas/farmacologia , Antivirais/farmacologia , Antivirais/química
13.
J Family Med Prim Care ; 11(6): 2900-2908, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36119180

RESUMO

Background: Diabetes is a costly and serious health problem that is increasing markedly. The quality of care is a major issue among diabetic patients. This study aims to assess the quality of care provided to diabetic patients using the American Diabetes Association (ADA) indicators. Methods: This was a cross-sectional study conducted using a retrospective chart review. The population was adult diabetic patients (type 2) who had attended the National Guard's primary healthcare centers, Makkah region, Saudi Arabia, from January 1, 2017, to December 31, 2018. Results: We studied 400 adult diabetic patients aged 30-97 years with a mean age of 58.25 (SD = 11.9). The length of time with diabetes ranged from 1 to 42 years with a mean of 9.66 years (SD = 7.6). Among all the primary healthcare centers (PHCs), specialized polyclinic (SPC) had the highest number of patient visits. Furthermore, the SPC had the highest number of patients with complications; the primary healthcare center with the fewest complications was Iskan-Jeddah. The results show that the control of hemoglobin A1C (HbA1C) was better in 2018 than in 2017. Conclusion: There is improved and adequate care provided to patients among the assessed primary healthcare centers in the Makkah region. Nevertheless, there remains a need for interventions to maintain comprehensive data on diabetes performance. Monitoring and proper education on diabetic care to patients are suggested to achieve better control of diabetes and delay the occurrence of complications.

14.
Ear Nose Throat J ; : 1455613221102869, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35570720

RESUMO

Complete laryngotracheal separation is a rare life-threatening trauma that may occur due to road traffic accidents. Unfortunately, this injury may be missed if emergency physicians were not aware of its possibility. We present a pediatric patient who had complete laryngotracheal separation and esophageal injury caused by strangulation with a headscarf while riding a four-wheeled motorcycle. The neck on external examination showed only a ligature mark without open wounds. The injury was identified while attempting tracheostomy as the patient had a decreased oxygen saturation and was aphonic. The patient underwent complete airway reconstruction and stenting as well as low tracheostomy with complete reconstruction and anastomosis of the esophagus. The patient was decannulated after a few weeks with the vocal cords in paramedian position and no aspiration. This case demonstrates that early prompt treatment can save the patient's life and result in good functional outcomes.

15.
J Med Chem ; 65(4): 2940-2955, 2022 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-34665619

RESUMO

Antiviral agents that complement vaccination are urgently needed to end the COVID-19 pandemic. The SARS-CoV-2 papain-like protease (PLpro), one of only two essential cysteine proteases that regulate viral replication, also dysregulates host immune sensing by binding and deubiquitination of host protein substrates. PLpro is a promising therapeutic target, albeit challenging owing to featureless P1 and P2 sites recognizing glycine. To overcome this challenge, we leveraged the cooperativity of multiple shallow binding sites on the PLpro surface, yielding novel 2-phenylthiophenes with nanomolar inhibitory potency. New cocrystal structures confirmed that ligand binding induces new interactions with PLpro: by closing of the BL2 loop of PLpro forming a novel "BL2 groove" and by mimicking the binding interaction of ubiquitin with Glu167 of PLpro. Together, this binding cooperativity translates to the most potent PLpro inhibitors reported to date, with slow off-rates, improved binding affinities, and low micromolar antiviral potency in SARS-CoV-2-infected human cells.


Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Inibidores de Cisteína Proteinase/farmacologia , Antivirais/síntese química , Antivirais/química , Sítios de Ligação/efeitos dos fármacos , COVID-19/metabolismo , Proteases Semelhantes à Papaína de Coronavírus/isolamento & purificação , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Cristalografia por Raios X , Inibidores de Cisteína Proteinase/síntese química , Inibidores de Cisteína Proteinase/química , Humanos , Testes de Sensibilidade Microbiana , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Modelos Moleculares , Pandemias , Ressonância de Plasmônio de Superfície , Células Tumorais Cultivadas
16.
Cureus ; 13(11): e19378, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34909325

RESUMO

Fibro-osseous lesions are common in the paranasal sinuses. The incidence of fibrous dysplasia (FD) in the ethmoid sinus is rare. Patients with such lesions are usually asymptomatic until the lesion is large enough to start compressing adjacent structures and organs. Common presentations include nasal obstruction, headache, eye swelling, and diplopia. Meanwhile, less common signs can include decreased visual acuity. We present a case of a 65-year-old male with comorbidities who presented to the clinic complaining of a chronic nasal obstruction, headache, and decreased visual acuity in the right eye. On endoscopic examination, a lesion was identified in the ethmoid sinus. Computed tomography was performed and confirmed the positioning of the lesion within the ethmoid sinus compressing the optic nerve. Total excision was performed through a direct nasal endoscopic approach. The lesion was excised completely with no recurrence. Histopathology report confirmed the lesion to be of cartilaginous nature, and a final diagnosis of cartilaginous fibrous osteoma was made. Such lesions are usually benign and symptomless. Excising the lesion completely is the best approach to decrease the chances of recurrence.

17.
Eur J Obstet Gynecol Reprod Biol ; 264: 88-96, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34298450

RESUMO

AIM: To meta-analytically examine the frequency and prognostic impact of preoperative leukocytosis in endometrial carcinoma (EC). METHODS: Five major databases were searched till 01-February-2021. Studies that evaluated the frequency of preoperative leukocytosis or its correlation with pathological and survival outcomes in EC patients were included. Data were pooled as mean differences (MD), odds ratios (OR), or hazard ratios (HR) with 95% confidence intervals. RESULTS: Nine retrospective studies, with low risk of bias, were included. The pooled prevalence of preoperative leukocytosis was 11.2% (95% CI: 8.2-14.3). There was a significant correlation between preoperative leukocytosis and FIGO stage III-IV (OR = 2.10, 95% CI: 1.60-2.75), ≥50% myometrial invasion (OR = 1.32, 95% CI: 1.02-1.72), lymph node involvement (OR = 1.83, 95% CI: 1.29-2.59), cervical involvement (OR = 2.29, 95% CI: 1.68-3.13), adnexal involvement (OR = 2.17, 95% CI: 1.42-3.31), and tumor size (MD = 1.10 cm, 95% CI: 0.63-1.58). However, preoperative leukocytosis did not significantly correlate with tumor grade II-III, non-endometrioid histology, peritoneal cytology, and lympho-vascular space involvement (p > 0.05). Additionally, preoperative leukocytosis correlated with higher rates of death (OR = 2.85, 95% CI: 2.03-4.00), tumor recurrence (OR = 2.36, 95% CI: 1.21-4.61), and worse overall survival at univariate and multivariate analyses (HR = 2.90, 95% CI: 2.24-3.75 and HR = 2.16, 95% CI: 1.59-2.94, respectively). As for disease-free survival, preoperative leukocytosis emerged as an independent prognostic factor on univariate (HR = 1.27, 95% CI: 1.16-1.39) but not multivariate (HR = 1.08, 95% CI: 1.00-1.18) analyses. CONCLUSIONS: Preoperative leukocytosis is common and correlates with poor pathological and survival outcomes in EC patients.


Assuntos
Neoplasias do Endométrio , Leucocitose , Neoplasias do Endométrio/patologia , Feminino , Humanos , Leucocitose/epidemiologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos
18.
bioRxiv ; 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33594371

RESUMO

Antiviral agents blocking SARS-CoV-2 viral replication are desperately needed to complement vaccination to end the COVID-19 pandemic. Viral replication and assembly are entirely dependent on two viral cysteine proteases: 3C-like protease (3CLpro) and the papain-like protease (PLpro). PLpro also has deubiquitinase (DUB) activity, removing ubiquitin (Ub) and Ub-like modifications from host proteins, disrupting the host immune response. 3CLpro is inhibited by many known cysteine protease inhibitors, whereas PLpro is a relatively unusual cysteine protease, being resistant to blockade by such inhibitors. A high-throughput screen of biased and unbiased libraries gave a low hit rate, identifying only CPI-169 and the positive control, GRL0617, as inhibitors with good potency (IC50 < 10 lower case Greek µM). Analogues of both inhibitors were designed to develop structure-activity relationships; however, without a co-crystal structure of the CPI-169 series, we focused on GRL0617 as a starting point for structure-based drug design, obtaining several co-crystal structures to guide optimization. A series of novel 2-phenylthiophene-based non-covalent SARS-CoV-2 PLpro inhibitors were obtained, culminating in low nanomolar potency. The high potency and slow inhibitor off-rate were rationalized by newly identified ligand interactions with a 'BL2 groove' that is distal from the active site cysteine. Trapping of the conformationally flexible BL2 loop by these inhibitors blocks binding of viral and host protein substrates; however, until now it has not been demonstrated that this mechanism can induce potent and efficacious antiviral activity. In this study, we report that novel PLpro inhibitors have excellent antiviral efficacy and potency against infectious SARS-CoV-2 replication in cell cultures. Together, our data provide structural insights into the design of potent PLpro inhibitors and the first validation that non-covalent inhibitors of SARS-CoV-2 PLpro can block infection of human cells with low micromolar potency.

19.
Saudi Med J ; 40(10): 1027-1031, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31588482

RESUMO

OBJECTIVES:   To investigate the prevalence and associated risk factors for venous thromboembolism (VTE) in burn patients.  Methods: This is a cross-sectional study eliciting the risk factors in burn patients who developed thromboembolism. The study took place at the Adult  Burn Unit, King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia. Charts of all patients admitted to the burn unit from January 2010 to December 2016 were reviewed. Only patients 16 years of age and older were included. The research team with a consultant plastic surgeon developed the data sheet. A total of 304 patient records met the inclusion criteria. Logistic regression analysis was used to determine the risk factors for developing VTE. Results: Out of the entire study group of 304 patients, the majority (88.8%) of the participants received prophylactic anticoagulation. Twelve patients (3.9%)  developed VTE. All patients who developed VTE received prophylactic anticoagulation. Age, gender, body mass index, and degree of burn were not risk factors for VTE. However, electric burns were found to be an independent significant risk factor for developing VTE using a multivariate logistic regression. Conclusion: Electric burns were found to be the only independent significant risk factor of developing VTE.


Assuntos
Unidades de Queimados/estatística & dados numéricos , Queimaduras/complicações , Tromboembolia/etiologia , Adulto , Anticoagulantes/uso terapêutico , Queimaduras/terapia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Fatores de Risco , Arábia Saudita/epidemiologia , Tromboembolia/epidemiologia , Tromboembolia/prevenção & controle
20.
Protein Sci ; 25(8): 1472-82, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27144666

RESUMO

The nucleosome remodeling and deacetylase (NuRD) complex remodels the genome in the context of both gene transcription and DNA damage repair. It is essential for normal development and is distributed across multiple tissues in organisms ranging from mammals to nematode worms. In common with other chromatin-remodeling complexes, however, its molecular mechanism of action is not well understood and only limited structural information is available to show how the complex is assembled. As a step towards understanding the structure of the NuRD complex, we have characterized the interaction between two subunits: the metastasis associated protein MTA1 and the histone-binding protein RBBP4. We show that MTA1 can bind to two molecules of RBBP4 and present negative stain electron microscopy and chemical crosslinking data that allow us to build a low-resolution model of an MTA1-(RBBP4)2 subcomplex. These data build on our understanding of NuRD complex structure and move us closer towards an understanding of the biochemical basis for the activity of this complex.


Assuntos
Histona Desacetilases/química , Nucleossomos/química , Subunidades Proteicas/química , Proteínas Repressoras/química , Proteína 4 de Ligação ao Retinoblastoma/química , Proteína 7 de Ligação ao Retinoblastoma/química , Sequência de Aminoácidos , Animais , Clonagem Molecular , Sequência Conservada , Reagentes de Ligações Cruzadas/química , Expressão Gênica , Células HEK293 , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Cinética , Modelos Moleculares , Mutação , Nucleossomos/metabolismo , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Estrutura Secundária de Proteína , Subunidades Proteicas/genética , Subunidades Proteicas/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Proteína 4 de Ligação ao Retinoblastoma/genética , Proteína 4 de Ligação ao Retinoblastoma/metabolismo , Proteína 7 de Ligação ao Retinoblastoma/genética , Proteína 7 de Ligação ao Retinoblastoma/metabolismo , Alinhamento de Sequência , Termodinâmica , Transativadores , Transcrição Gênica
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