Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 27
Filtrar
1.
Cancers (Basel) ; 16(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893280

RESUMO

Despite the high tobacco use rates (~80%) and tobacco-related cancers being the second leading cause of death among people experiencing homelessness within the United States, these individuals rarely receive tobacco use treatment from homeless-serving agencies (HSAs). This qualitative study explored the enablers and inhibitors of implementing an evidence-based tobacco-free workplace (TFW) program offering TFW policy adoption, specialized provider training to treat tobacco use, and nicotine replacement therapy (NRT) within HSAs. Pre- and post-implementation interviews with providers and managers (n = 13) pursued adapting interventions to specific HSAs and assessed the program success, respectively. The organizational readiness for change theory framed the data content analysis, yielding three categories: change commitment, change efficacy and contextual factors. Pre- to post-implementation, increasing challenges impacted the organizational capacity and providers' attitudes, wherein previously enabling factors were reframed as inhibiting, resulting in limited implementation despite resource provision. These findings indicate that low-resourced HSAs require additional support and guidance to overcome infrastructure challenges and build the capacity needed to implement a TFW program. This study's findings can guide future TFW program interventions, enable identification of agencies that are well-positioned to adopt such programs, and facilitate capacity-building efforts to ensure their successful participation.

2.
Transl Behav Med ; 14(7): 394-401, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38757794

RESUMO

Tobacco-free workplace policies (TFWPs) are underused evidence-based interventions that reduce the elevated use of tobacco among substance use treatment center (SUTC) employees and patients. SUTC employees' anticipated concerns about stakeholder pushback are barriers to TFWP adoption. Examination of discrepancies between anticipated and actualized employee-reported TFWP concerns arising from coworkers, patients, and community members in the context of leadership concerns and tobacco cessation care availability for employees may inform strategies to increase TFWP uptake. This study analyzed changes in employee-reported TFWP concerns from before to after a comprehensive tobacco-free workplace intervention that included TFWP implementation, using Chi-square/Fisher's exact tests. Preimplementation leadership policy concerns and tobacco cessation care availability were examined as moderators in generalized linear mixed models. Overall, 452 employees and 13 leaders provided data from 13 SUTCs collectively serving >82 000 patients annually. Results revealed significant decreases over time in employee-reported concerns about TFWP resistance from coworkers. Moderation analyses indicated that employee-anticipated concerns from coworkers and patients, respectively, were less likely to be actualized in SUTCs where leadership endorsed preimplementation TFWP concerns, whereas employee-reported patient concerns rose over time in SUTCs where leadership had no initial implementation concerns. Additionally, employee-anticipated concerns from coworkers were overestimated in SUTCs that did not offer tobacco cessation care to employees. Results supporting the nonactualization of anticipated employee concerns following TFWP implementation can be used to engage other SUTCs for TFWP adoption. Furthermore, moderation effects may suggest that center characteristics translate to greater attention to rollout, ultimately enhancing TFWP stakeholder acceptance.


Substance use treatment center (SUTC) employees and patients use tobacco at elevated rates and suffer disproportionately from tobacco-related diseases. The implementation of a tobacco-free workplace policy (TFWP) can reduce tobacco use disparities in this setting. However, employee concerns about TFWPs are often a deterrent to their adoption. This study assessed how employee-reported concerns changed over time and whether these changes differed based on center characteristics like center leadership concerns about the TFWP and availability of tobacco cessation services for employees. Overall, the most common employee-reported concerns were those arising from patients, followed by coworkers and community members throughout policy implementation. Results demonstrated that anticipated concerns from coworkers decreased over time in all SUTCs. Furthermore, TFWP concerns from coworkers and patients were overestimated by employees at centers wherein leadership had concerns about TFWP implementation, whereas patient concerns were underestimated at centers where leadership had no preimplementation concerns. Finally, employee-anticipated concerns from coworkers were overestimated in SUTCs without tobacco cessation care for employees. Findings suggest that employees may overestimate concerns/complaints from various stakeholders based on organizational factors. This information may be used to engage additional SUTCs in TFWP implementation by alleviating employee concerns about policy adoption.


Assuntos
Liderança , Local de Trabalho , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Abandono do Uso de Tabaco/métodos , Política Organizacional , Política Antifumo , Abandono do Hábito de Fumar/métodos
3.
Pathol Res Pract ; 253: 155018, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38070222

RESUMO

Tumorigenesis exemplifies the complex process of neoplasm origination, which is characterised by somatic genetic alterations and abnormal cellular growth. This multidimensional phenomenon transforms previously dormant cells into malignant equivalents, resulting in uncontrollable proliferation and clonal expansion. Various elements, including random mutations, harmful environmental substances, and genetic predispositions, influence tumorigenesis's aetiology. MicroRNAs (miRNAs) are now recognised as crucial determinants of gene expression and key players in several biological methods, including oncogenesis. A well-known hypoxia-inducible miRNA is MiR-210, which is of particular interest because of its complicated role in the aetiology of cancer and a variation of physiological and pathological situations. MiR-210 significantly impacts cancer by controlling the hypoxia-inducible factor (HIF) signalling pathway. By supporting angiogenesis, metabolic reprogramming, and cellular survival in hypoxic microenvironments, HIF signalling orchestrates adaptive responses, accelerating the unstoppable development of tumorous growth. Targeting several components of this cascade, including HIF-1, HIF-3, and FIH-1, MiR-210 plays a vital role in modifying HIF signalling and carefully controlling the HIF-mediated response and cellular fates in hypoxic environments. To understand the complexities of this relationship, careful investigation is required at the intersection of MiR-210 and HIF signalling. Understanding this relationship is crucial for uncovering the mechanisms underlying cancer aetiology and developing cutting-edge therapeutic approaches. The current review emphasises MiR-210's significance as a vital regulator of the HIF signalling cascade, with substantial implications spanning a range of tumor pathogenesis.


Assuntos
MicroRNAs , Neoplasias , Humanos , MicroRNAs/metabolismo , Transdução de Sinais/genética , Neoplasias/genética , Hipóxia , Hipóxia Celular , Carcinogênese/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/genética , Microambiente Tumoral/genética
4.
Artigo em Inglês | MEDLINE | ID: mdl-36901024

RESUMO

Tobacco use is the leading preventable cause of death in America and is elevated among patients with non-tobacco substance use disorders. Substance use treatment centers (SUTCs) do not commonly address their patients' tobacco use. Lack of knowledge on treating tobacco use with counseling and medication may be a barrier that underlies this inaction. A multi-component tobacco-free workplace program implemented in Texas SUTCs educated providers on treating tobacco use with evidence-based medication (or referral) and counseling. This study examined how center-level changes in knowledge from pre- to post-implementation (i.e., over time) affected center-level behavioral changes in providers' provision of tobacco use treatment over time. Providers from 15 SUTCs completed pre- and post-implementation surveys (pre N = 259; post N = 194) assessing (1) perceived barriers to treating tobacco use, specifically, a lack of knowledge on treating tobacco use with counseling or medication; (2) receipt of past-year education on treating tobacco use with counseling or medication; and (3) their intervention practices, specifically, the self-reported regular use of (a) counseling or (b) medication intervention or referral with patients who use tobacco. Generalized linear mixed models explored associations between provider-reported knowledge barriers, education receipt, and intervention practices over time. Overall, recent counseling education receipt was endorsed by 32.00% versus 70.21% of providers from pre- to post-implementation; the regular use of counseling to treat tobacco use was endorsed by 19.31% versus 28.87% from pre- to post-implementation. Recent medication education receipt was endorsed by 20.46% versus 71.88% of providers from pre- to post-implementation; the regular use of medication to treat tobacco use was endorsed by 31.66% versus 55.15% from pre- to post-implementation. All changes were statistically significant (ps < 0.05). High versus low reductions in the provider-reported barrier of "lack of knowledge on pharmacotherapy treatment" over time were a significant moderator of effects, such that SUTCs with high reductions in this barrier were more likely to report greater increases in both medication education receipt and medication treatment/referral for patients who use tobacco over time. In conclusion, a tobacco-free workplace program implementation strategy that included SUTC provider education improved knowledge and resulted in increased delivery of evidence-based treatment of tobacco use at SUTCs; however, treatment provision rates-in particular, offering tobacco cessation counseling-remained less than desirable, suggesting that barriers beyond lack of knowledge may be important to address to improve tobacco use care in SUTCs. Moderation results suggest (1) differences in the mechanisms underlying uptake of counseling education versus medication education and (2) that the relative difficulty of providing counseling versus providing medication persists regardless of knowledge gains.


Assuntos
Abandono do Hábito de Fumar , Transtornos Relacionados ao Uso de Substâncias , Humanos , Abandono do Hábito de Fumar/métodos , Aconselhamento/métodos , Uso de Tabaco
5.
Artigo em Inglês | MEDLINE | ID: mdl-36768097

RESUMO

Tobacco use treatment is not prioritized in substance use treatment centers (SUTCs), leading to tobacco-related health inequities for patients with substance use disorders (SUDs) and necessitating efforts to enhance providers' care provision. Training providers on how to treat tobacco use increases their intervention on patients' smoking, but limited work addresses its effects on their non-cigarette tobacco use intervention provision. This study redressed this gap using data from 15 unaffiliated SUTCs in Texas (serving 82,927 patients/year) participating in a tobacco-free workplace program (TFWP) that included provider education on treating tobacco use, including non-cigarette tobacco use. SUTC providers completed surveys before (n = 259) and after (n = 194) TFWP implementation. Past-month screening/intervention provision for non-cigarette tobacco use (the 5A's; ask, advise, assess, assist, arrange) and provider factors theoretically and practically presumed to underlie change [i.e., beliefs about concurrently treating tobacco use disorder (TUD) and other SUDs, self-efficacy for tobacco use assessment (TUA) delivery, barriers to treating tobacco dependence, receipt of tobacco intervention training] were assessed. Generalized linear or linear mixed models assessed changes over time from before to after TFWP implementation; low vs. high SUTC-level changes in provider factors were examined as moderators of changes in 5A's delivery. Results indicated significant improvement in each provider factor and increases in providers' asking, assisting, and arranging for non-cigarette tobacco use over time (ps < 0.04). Relative to their counterparts, SUTCs with high changes in providers' beliefs in favor of treating patients' tobacco use had greater odds of advising, assessing, assisting, and arranging patients, and SUTCs with greater barrier reductions had greater odds of advising and assisting patients. Results suggest that TFWPs can address training deficits and alter providers' beliefs about treating non-tobacco TUD during SUD care, improve their TUA delivery self-efficacy, and reduce intervention barriers, ultimately increasing intervention provision for patients' non-cigarette tobacco use. SUTCs with the greatest room for improvement in provider beliefs and barriers to care provision seem excellent candidates for TFWP implementation aimed at increasing non-cigarette tobacco use care delivery.


Assuntos
Abandono do Hábito de Fumar , Tabagismo , Humanos , Nicotiana , Abandono do Hábito de Fumar/métodos , Tabagismo/epidemiologia , Tabagismo/terapia , Local de Trabalho , Fumar Tabaco
6.
Artigo em Inglês | MEDLINE | ID: mdl-36293643

RESUMO

Black women have a slightly lower breast cancer incidence rate than White women, but breast cancer mortality is approximately 40% higher among Black women than among White women. Early detection by mammography may improve survival outcomes. Outlets providing information on cancer and cancer screening often present data, including mammography recommendations, that are unreliable, accessible, and/or inconsistent. We examined associations between sources of cancer information and mammography behavior among Black church-going women. A logistic regression model was used to examine associations between self-reported preferred source of cancer information (provider, cancer organization, social network, internet, or other media (e.g., books, magazines)) and self-reported most recent source of cancer information (same categories as preferred sources), respectively, and having received a mammogram within the prior 12 months. Participants were 832 Black women over 40 years old, recruited from three churches in Houston, Texas. Data were collected in 2012. Overall, 55.41% of participants indicated their preferred source of cancer information was a provider, 21.88% the internet, 11.54% other media, 10.22% a cancer organization, and 0.96% their social network. In contrast, 17.88% of participants indicated their most recent source of cancer information was a provider, 63.02% the internet, 12.04% other media, 4.50% a cancer organization, and 2.55% their social network. About 70% of participants indicated receiving a mammogram in the prior 12 months. Results indicated that women who most recently sought information from the internet had lower odds of having a mammogram than those who most recently sought information from a provider (aOR: 0.546, CI95%: 0.336-0.886, p = 0.014). These results reveal an opportunity to advance health equity by encouraging Black church-going women to obtain cancer information from providers rather than from the internet as a method to enhance mammography use. These results also reveal an opportunity to investigate what modifiable social determinants or other factors prevent Black church-going women from seeking cancer information from their preferred source, which was a provider for the majority of the sample, and designing interventions to better actualize this preference.


Assuntos
Neoplasias da Mama , Mamografia , Feminino , Humanos , Adulto , Detecção Precoce de Câncer , Neoplasias da Mama/diagnóstico , Negro ou Afro-Americano , População Negra , Programas de Rastreamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-35955001

RESUMO

Tobacco use, and thus tobacco-related morbidity, is elevated amongst patients with behavioral health treatment needs. Consequently, it is important that centers providing health care to this group mandate providers' use of tobacco screenings to inform the need for tobacco use disorder intervention. This study examined the prevalence of mandated tobacco screenings in 80 centers providing health care to Texans with behavioral health needs, examined key factors that could enhance screening conduct, and delineated providers' perceived barriers to tobacco use intervention provision. The results indicated that 80% of surveyed centers mandated tobacco use screenings; those that did were significantly more likely than those that did not to have a hard stop for tobacco use status in health records and were marginally more likely to make training on tobacco screening available to providers. The most widespread barriers to tobacco use disorder care provision were relative perceived importance of competing diagnoses, lack of community resources to refer patients, perceived lack of time, lack of provider knowledge or confidence, and belief that patients do not comply with cessation treatment. Overall, the results suggest that there are opportunities for centers providing care to Texans with behavioral health needs to bolster their tobacco screening and intervention capacity to better address tobacco-related health disparities in this group. Health care centers can support their providers to intervene in tobacco use by mandating screenings, streamlining clinical workflows with hard stops in patient records, and educating providers about the importance of treating tobacco with brief evidence-based intervention strategies while providing accurate information about patients' interest in quitting and providers' potential impacts on a successful quit attempt.


Assuntos
Abandono do Uso de Tabaco , Tabagismo , Atenção à Saúde , Humanos , Texas , Nicotiana , Uso de Tabaco , Tabagismo/epidemiologia
8.
Cureus ; 14(7): e27149, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36017269

RESUMO

Background One of the most commonly used classes of medications that are known for their excessively expanded misuse is proton pump inhibitors (PPIs). Although they are profoundly useful, they also account for several adverse effects. Assessing the awareness of the general population may throw light on the problem and limit irrational use. This study aims to determine the knowledge, attitude, and behavior of the general population of Saudi Arabia regarding PPI use. Materials and methods This was a descriptive cross-sectional study using a structured online survey. The questionnaire comprised 1088 participants of the adult general population of Saudi Arabia to assess knowledge and awareness of proton pump inhibitors.  Results Of the 1088 participants, 59% were men and 41% were women, 44.6% were aged 20-30 years, 25.4% were 31-40 years, and 16% were 41-50 years. Only 54% of the participants had previous knowledge of PPIs. Regarding PPI use, 25.7% of participants previously used PPIs with medical consultation and 10.3% without medical consultation, while 64% had never used PPIs. Reasons for PPI use included: heartburn (56.4%), gastroesophageal reflux disease (51.1%), gastritis (21.8%), as part of Helicobacter pylori infection therapy (20%), peptic ulcer (15.7%), esophagitis (7.1%), sore throat (6.1%), gastroenteritis (5.4%), hiatal hernia (5%), hoarseness (3.2%), asthma (2.1%), and bariatric surgery (2.1%). Of all the participants, 61.2% completed the treatment course while 38.8% did not. Conclusion Generally, our population had moderate knowledge of PPI. However, it is not enough to eliminate this irrational use of PPIs.This study emphasizes the importance of effective provider-led patient education to raise awareness of potential risks and reduce inappropriate long-term use of PPIs. This is significant due to growing concern about the possibility of medication overuse and non-compliance due to a lack of awareness about PPIs. In addition, more research assessing the awareness of over-the-counter (OTC) medications should be taken into consideration.

9.
J Mol Struct ; 1246: 131113, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34305174

RESUMO

At the very beginning of the new decade, the COVID-19 pandemic has badly hit modern human societies. SARS-CoV-2, the causative agent of COVID-19 acquiring mutations and circulating as new variants. Herein, we have found three new antiviral peptides (AVPs) against the SARS-CoV-2. These AVPs are analogous to the spike glycoprotein of the SARS-CoV-2. Antiviral peptides, i.e., Seq12, Seq12m, and Seq13m, can block the receptor-binding domain (RBD) of the SARS-CoV-2, which is necessary for communicating with the angiotensin-converting enzyme 2 (ACE2). Also, these AVPs sustain their antiviral properties, even after the insertion of 25 mutations in the RBD (Rosetta and FoldX based). Further, Seq12 and Seq12m showed negligible cytotoxicity. Besides, the binding free energies calculated using MM-PB/GBSA method are also in agreement with the molecular docking studies. The molecular interactions between AVPs and the viral membrane protein (M) also showed a favorable interaction suggesting it could inhibit the viral re-packaging process. In conclusion, this study suggests Seq12, Seq12m, and Seq13m could be helpful to fight against SARS-CoV-2. These AVPs could also aid virus diagnostic tools and nasal spray against SARS-CoV-2 in the future.

10.
J Mol Graph Model ; 106: 107937, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34049193

RESUMO

Class IIa histone deacetylases (HDACs) 5 and 9 play crucial roles in several human disorders such as cancer, making them important targets for drug design. Continuous research is pursed to overcome the cytotoxicity side effect that comes with the currently available broad-spectrum HDACs inhibitors. Herein, common features of active HDACs inhibitors in clinical trials and use have been calculated to generate the best pharmacophore hypothesis. Guner-Henry scoring system was used to validate the generated hypotheses. Hypo1 of HDAC5 and Hypo2 of HDAC9 exhibited the most statistically significance hypotheses. Compounds with fit value of 3 and more were examined by QuickVina 2 docking tool to calculate their binding affinity toward all class IIa HDACs. A total of 6 potential selective compounds were subjected to 100 molecular dynamics (MD) simulation to examine their binding modes. The free binding energy calculations were computed according to the MM-PBSA method. Proposed selective compounds displayed good stability with their targets and thus they may offer potent leads for the designing of HDAC5 and HDAC9 isoform selective inhibitors.


Assuntos
Simulação de Dinâmica Molecular , Neoplasias , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Humanos , Ligantes , Simulação de Acoplamento Molecular , Neoplasias/tratamento farmacológico , Isoformas de Proteínas
11.
Comput Biol Chem ; 92: 107491, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33930743

RESUMO

The fundamental cause of human cancer is strongly influenced by down- or up-regulations of epigenetic factors. Upregulated histone deacetylases (HDAC) have been shown to be effectively neutralized by the action of HDACs inhibitors (HDACi). However, cytotoxicity has been reported in normal cells because of non-specificity of several available HDACis that are in clinical use or at different phases of clinical trials. Because of the high amino acid sequence and structural similarity among HDAC enzymes, it is believed to be a challenging task to obtain isoform-selectivity. The essential aim of the present research work was to identify isoform-selective inhibitors against class IIa HDACs via structure-based drug design. Based on the highest binding affinity and isoform-selectivity, the top-ranked inhibitors were in silico tested for their absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, which were classified as drug-like compounds. Later, molecular dynamics simulation (MD) was carried out for all compound-protein complexes to evaluate the structural stability and the biding mode of the inhibitors, which showed high stability throughout the 100 ns simulation. Free binding energy predictions by MM-PBSA method showed the high binding affinity of the identified compounds toward their respective targets. Hence, these inhibitors could be used as drug candidates or as lead compounds for more in silico or in vitro optimization to design safe isoform-selective HDACs inhibitors.


Assuntos
Antineoplásicos/farmacologia , Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos/química , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/química , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Simulação de Dinâmica Molecular , Estrutura Molecular , Neoplasias/metabolismo , Termodinâmica
12.
J Biomol Struct Dyn ; 39(17): 6396-6414, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-32715940

RESUMO

Histone deacetylases (HDACs) are a group of enzymes that have prominent and crucial effect on various biological systems, mainly by their suppressive effect on transcription. Searching for inhibitors targeting their respective isoforms without affecting other targets is greatly needed. Some histone deacetylases have no crystal structures, such as HDAC5 and HDAC9. Lacking proper and suitable crystal structure is obstructing the designing of appropriate isoform selective inhibitors. Here in this study, we constructed human HDAC5 and HDAC9 protein models using human HDAC4 (PDB:2VQM_A) as a template by the means of homology modeling approach. Based on the Z-score of the built models, model M0014 of HDAC5 and model M0020 of HDAC9 were selected. The models were verified by MODELLER and validated using the Web-based PROCHECK server. All selected known inhibitors displayed reasonable binding modes and equivalent predicted Ki values in comparison to the experimental binding affinities (Ki/IC50). The known inhibitor Rac26 showed the best binding affinity for HDAC5, while TMP269 showed the best binding affinity for HDAC9. The best two compounds, CHEMBL2114980 and CHEMBL217223, had relatively similar inhibition constants against HDAC5 and HDAC9. The built models and their complexes were subjected to molecular dynamic simulations (MD) for 100 ns. Examining the MD simulation results of all studied structures, including the RMSD, RMSF, radius of gyration and potential energy suggested the stability and reliability of the built models. Accordingly, the results obtained in this study could be used for designing de novo inhibitors against HDAC5 and HDAC9. Communicated by Ramaswamy H. Sarma.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/química , Histona Desacetilases/metabolismo , Humanos , Isoenzimas , Simulação de Dinâmica Molecular , Proteínas Repressoras/genética , Reprodutibilidade dos Testes
13.
J Biomol Struct Dyn ; 39(11): 4100-4110, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32462974

RESUMO

γ-aminobutyric acid aminotransferase (GABA-AT) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme which degrades γ-aminobutyric (GABA) in the brain. GABA is an important inhibitory neurotransmitter that plays important neurological roles in the brain. Therefore, GABA-AT is an important drug target which regulates the GABA level. Novel and potent drug development to inhibit GABA-AT is still very challenging task. In this study, we aimed to devise novel and potent inhibitors against GABA-AT using computer-aided drug design (CADD) tools. However, the human GABA-AT crystal structure is not available yet, and we built the 3D structure of human GABA-AT based on the crystal structure of pig's liver (Sus Scrofa) enzyme as a template. The generated model was validated with numerous tools such as ProSA and PROCHECK. A set of selected well-known inhibitors have been tested against the modeled GABA-AT. Molecular docking studies have been accomplished via application of Genetic Optimization for Ligand Docking (GOLD), Vina and Autodock 4.2 software to search for potent inhibitors. The best two candidate inhibitors have been computationally examined for absorption, distribution, metabolism, elimination and toxicity descriptors (ADMET) and Lipinski's rule of 5. Lastly, molecular dynamics (MD) simulations were carried out to inspect the ligands' binding mode and stability of the active site of human GABA-AT over time. The top ranked ligands exhibited reliable stability throughout the MD simulation. The selected compounds are promising candidates and might be tested experimentally for the inhibition of human GABA-AT enzyme. Communicated by Ramaswamy H. Sarma.


Assuntos
Desenho de Fármacos , Simulação de Dinâmica Molecular , Humanos , Ligantes , Simulação de Acoplamento Molecular , Transaminases , Ácido gama-Aminobutírico
14.
J Biomol Struct Dyn ; 39(8): 2980-2992, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-32306862

RESUMO

In December 2019, COVID-19 epidemic was described in Wuhan, China, and the infection has spread widely affecting hundreds of thousands. Herein, an effort was made to identify commercially available drugs in order to repurpose them against coronavirus by the means of structure-based virtual screening. In addition, ZINC15 library was used to identify novel leads against main proteases. Human TMPRSS2 3D structure was first generated using homology modeling approach. Our molecular docking study showed four potential inhibitors against Mpro enzyme, two available drugs (Talampicillin and Lurasidone) and two novel drug-like compounds (ZINC000000702323 and ZINC000012481889). Moreover, four promising inhibitors were identified against TMPRSS2; Rubitecan and Loprazolam drugs, and compounds ZINC000015988935 and ZINC000103558522. ADMET profile showed that the hits from our study are safe and drug-like compounds. Furthermore, molecular dynamic (MD) simulation and binding free energy calculation using the MM-PBSA method was performed to calculate the interaction energy of the top-ranked drugs.Communicated by Ramaswamy H. Sarma.


Assuntos
COVID-19 , Preparações Farmacêuticas , Cisteína Endopeptidases , Reposicionamento de Medicamentos , Humanos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases , Inibidores de Proteases/farmacologia , SARS-CoV-2 , Proteínas não Estruturais Virais
15.
Saudi Med J ; 41(4): 431-434, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32291432

RESUMO

OBJECTIVES:  To estimate the prevalence of hypocalcemia following total thyroidectomy (TT) at a tertiary center. METHODS: This retrospective study was conducted between 2014 and 2019 at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia. The study was based at the Department of General Surgery and was approved by the Research Ethics Committee of KAUH. Medical records of 154 patients who had undergone TT were reviewed. Data such as age, gender, level of postoperative calcium at 24 and 48 hours after surgery, parathyroid hormone (PTH) levels, central neck dissection (CCND), histological diagnosis were entered into Microsoft Excel sheets. RESULTS:  Hypocalcemia occurred more on the second day after surgery in 67.4% of patients. Among them, 83.9% were female and 16.1% were male. The majority of patients were asymptomatic and benign thyroid disease was the most common. There was a significant association between hypocalcemia and the PTH level (p less than 0.001). CONCLUSION:  There was a high prevalence of hypocalcemia on the second day after surgery. Presence of hypocalcemia association with the PTH level. Meticulous surgical technique and preservation of parathyroid vascularity are important in preventing postoperative hypocalcemia.


Assuntos
Hipocalcemia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Tireoidectomia , Adulto , Fatores Etários , Cálcio/metabolismo , Feminino , Humanos , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/metabolismo , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Prevalência , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Fatores Sexuais , Tireoidectomia/efeitos adversos
16.
Animal ; 12(7): 1424-1434, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29173213

RESUMO

Roundup is a glyphosate-based herbicide (GBH) widely used in agriculture and may cause toxic effects in non-target organisms. Model organisms, as zebrafish, and analysis of gene expression by reverse transcription-quantitative PCR (RT-qPCR) could be used to better understand the Roundup toxicity. A prerequisite for RT-qPCR is the availability of appropriate reference genes; however, they have not been described for Roundup-exposed fish. The aim of this study was to evaluate the expression stability of six reference genes (rpl8, ß-act, gapdh, b2m, ef1α, hprt1) and one expressed repetitive element (hatn10) in organs of males (brain, gill, testis) and females (ovary) of zebrafish exposed to Roundup WG at three concentrations (0.065, 0.65 and 6.5 mg N-(phosphonomethyl) glycine/l) for 7 days. Genes were ranked by geNorm, NormFinder, BestKeeper, Delta C t and RefFinder, and their best combinations were determined by geNorm and NormFinder programs. The two most stable ranked genes were specific to each organ: gill (ß-act; rpl8); brain (rpl8; ß-act); testis (ef1α; gapdh); and ovary (rpl8; hprt1). The cat transcript level was used to evaluate the effect of normalization with these reference genes. These are the first suitable reference genes described for the analysis of gene expression in organs of Roundup-exposed zebrafish, and will allow investigations of the molecular mechanisms of Roundup toxicity.


Assuntos
Perfilação da Expressão Gênica , Glicina/análogos & derivados , Reação em Cadeia da Polimerase em Tempo Real , Peixe-Zebra , Animais , Feminino , Glicina/toxicidade , Herbicidas , Masculino , Padrões de Referência , Transcrição Reversa , Peixe-Zebra/genética , Glifosato
17.
J Contemp Dent Pract ; 18(6): 429-436, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28621269

RESUMO

AIM: The effect of Khat and Shammah habits, with the para-functional jaw activities that accompany them, on the structure and integrity of the natural dentition has not yet been investigated. The literature lacks studies that identify the patterns of tooth wear among Khat and Shammah users. Therefore, this study is the first attempt to address this concern in Jazan City population, Kingdom of Saudi Arabia. MATERIALS AND METHODS: A cross-sectional survey study was conducted among 300 recruits among dental clinics in Jazan City, Kingdom of Saudi Arabia from October 1, 2015, to April 30, 2016. Questionnaires were used for data collection on oral habits (Khat and Shammah use), age, gender, intake of acidic food or beverages, food habits (intake of fruits, grains, and vegetables), systemic diseases, oral hygiene habits (brushing frequency, technique, and type of toothbrush), parafunctional habits, stress, and acid reflux. Clinical examination was performed to assess the grade of tooth wear. Bivariate analysis was performed to determine the empirical relationship between the independent variables and outcomes. In addition, binary logistic regressions were used to measure the relationship between the independent variables and each of the dependent variables (presence of occlusal wear, tooth wear grade 0 through 4). RESULTS: Khat and Shammah use was statistically significantly associated with tooth wear (p < 0.05). A significant association of tooth wear was observed with age, gender, intake of acidic food and beverages, oral hygiene habits, and stress. CONCLUSION: Consumption of Khat and Shammah may be attributed as one of the major reasons associated with tooth wear among the Saudi population. CLINICAL SIGNIFICANCE: The habitual use of Khat and Shammah causes tooth wear of varying severity, which may negatively affect esthetics, phonetics, and function and necessitate a complex restorative treatment.


Assuntos
Catha , Mastigação , Folhas de Planta , Tabaco sem Fumaça/efeitos adversos , Desgaste dos Dentes/etiologia , Adulto , Fatores Etários , Idoso , Estudos Transversais , Dieta/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Arábia Saudita/epidemiologia , Fatores Sexuais , Estresse Psicológico/complicações , Inquéritos e Questionários , Desgaste dos Dentes/epidemiologia
18.
Lab Med ; 46(1): 8-13, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25617386

RESUMO

ß-thalassemia is a common hereditary disorder, particularly in Middle Eastern countries. More than 200 mutations in the ß globin gene have been reported; most are point mutations in functionally important regions (HBB; OMIM #141900)). The spectrum of mutations varies significantly between different geographical regions; only a few common mutations of ß-globin cause ß-thalassemia in each population. The aim of this study was to determine the spectrum of mutations that cause ß-thalassemia in the North Coast of Egypt and to investigate their correlation with the phenotypic severity of ß-thalassemia. We carried out our study with a total of 47 Egyptian patients (25 male and 22 female) confirmed to have ß-thalassemia. Evaluation of ß-thalassemia mutations revealed the presence of 10 ß-globin mutations. The most frequently encountered mutations were intronic: IVS 1.6 [T>C] (27.66%) and IVS 1.110 [G>A] (22.35%), followed by IVS 2.848 [C>A], IVS 1.1 (G>A), and IVS 2.745 [C>G]. We observed the exonic and promoter mutations less frequently. A homozygous mutation was found in 24 patients (51%) and compound heterozygous mutations were found in 13 patients (28%). However, in 9 patients (19%), we identified only 1 mutation. In 1 patient (2%), we detected no mutation. The detection rate of the method that we used in our population was 88% (83 of the tested 94 alleles). The results we obtained did not reveal any correlation between genotype and phenotype among patients with ß-thalassemia.


Assuntos
Mutação/genética , Globinas beta/genética , Talassemia beta/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Análise Mutacional de DNA , Egito , Feminino , Genótipo , Humanos , Masculino , Fenótipo , Adulto Jovem
20.
Sahara J (Online) ; 8(2): 74-81, 2011.
Artigo em Inglês | AIM (África) | ID: biblio-1271500

RESUMO

Prisons often lack the basic health services required by HIV/AIDS patients. As with many other chronic illnesses; the treatment of HIV is expensive in terms of medication; hygiene; testing and staff training. Strategies to combat the disease have been thoroughly developed; particularly in Europe (WHO/UNAIDS; 2006). The purpose of this study was to assess quality of life (QOL) of the only 5 reported cases of HIV/AIDS patients in Roumieh prison (the country's largest male top-security prison) using the WHOQOL and the WHO guidelines on HIV infection and AIDS in prison. Virtually all prisoners reported that their rights had been violated. Isolation measures were taken to prevent the spread of the disease. According to UNAIDS; this particular measure has been proven ineffective. In conclusion; other approaches should be implemented to respect inmates' rights and reduce transmission of the virus


Assuntos
HIV , Síndrome da Imunodeficiência Adquirida , Transmissão de Doença Infecciosa , Infecções por HIV , Violação de Direitos Humanos , Prisioneiros , Qualidade da Assistência à Saúde , Qualidade de Vida
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...