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1.
Org Biomol Chem ; 21(41): 8335-8343, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37800473

RESUMO

Readily available 3-alkylideneoxindoles were effectively reduced to 3-alkyloxindoles through transfer hydrogenation using Hantzsch ester as a reducing agent at ambient temperature and the greenness/sustainability of this protocol was assessed by correlation with Pd/C-mediated hydrogenation with hydrogen gas. Furthermore, an organocatalytic method was developed to access drug-like 3-alkyl-3-hydroxyoxindoles by C-H oxidation of 3-alkyl-indolin-2-one, using a catalytic amount of 1,1,3,3-tetramethylguanidine (TMG) as an organic base and dissolved oxygen in THF as an oxidant at room temperature. Key reaction intermediates were observed by controlled on-line ESI-HRMS experiments and identified by their corresponding mass (m/z) analysis. This two-step high-yielding transfer hydrogenation/C-H oxidation protocol was used for the total synthesis of medicinally important 3-cyanomethyl-3-hydroxyoxindole and formal total synthesis of (±)-alline and (±)-CPC-I in very good overall yields compared to previous methods.

2.
Adv Healthc Mater ; 12(31): e2302271, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37709282

RESUMO

3D bioprinting is revolutionizing the fields of personalized and precision medicine by enabling the manufacturing of bioartificial implants that recapitulate the structural and functional characteristics of native tissues. However, the lack of quantitative and noninvasive techniques to longitudinally track the function of implants has hampered clinical applications of bioprinted scaffolds. In this study, multimaterial 3D bioprinting, engineered nanoparticles (NPs), and spectral photon-counting computed tomography (PCCT) technologies are integrated for the aim of developing a new precision medicine approach to custom-engineer scaffolds with traceability. Multiple CT-visible hydrogel-based bioinks, containing distinct molecular (iodine and gadolinium) and NP (iodine-loaded liposome, gold, methacrylated gold (AuMA), and Gd2 O3 ) contrast agents, are used to bioprint scaffolds with varying geometries at adequate fidelity levels. In vitro release studies, together with printing fidelity, mechanical, and biocompatibility tests identified AuMA and Gd2 O3 NPs as optimal reagents to track bioprinted constructs. Spectral PCCT imaging of scaffolds in vitro and subcutaneous implants in mice enabled noninvasive material discrimination and contrast agent quantification. Together, these results establish a novel theranostic platform with high precision, tunability, throughput, and reproducibility and open new prospects for a broad range of applications in the field of precision and personalized regenerative medicine.


Assuntos
Bioimpressão , Iodo , Camundongos , Animais , Bioimpressão/métodos , Reprodutibilidade dos Testes , Engenharia Tecidual/métodos , Tomografia Computadorizada por Raios X , Impressão Tridimensional , Tecidos Suporte/química
3.
Mol Biol (Mosk) ; 57(4): 689-691, 2023.
Artigo em Russo | MEDLINE | ID: mdl-37528789

RESUMO

Ras proteins are small GTPases and function as molecular switches to regulate cellular homeostasis. Ras-dependent signalling pathways regulate several essential processes such as cell cycle progression, growth, migration, apoptosis, and senescence. The dysregulation of Ras signaling pathway has been linked to several pathological outcomes. A potential role of RAS in regulating the redox signalling pathway has been established that includes the manipulation of ROS levels to provide a redox milieu that might be conducive to carcinogenesis. Reactive oxygen species (ROS) and mitochondrial impairment have been proposed as major factors affecting the physiology of cells and implicated in several pathologies. The present study was conducted to evaluate the role of Ras1, tert Butyl hydroperoxide (tBHP), and antimycin A in oxidative stress response in Schizosaccharomyces pombe cells. We observed decreased cell survival, higher levels of ROS, and mitochondrial dysfunctionality in ras1Δ cells and tBHP as well as respiratory inhibitor, antimycin A treated wild type cells. Furthermore, these defects were more profound in ras1Δ cells treated with tBHP or antimycin A. Additionally, Ras1 also has been shown to regulate the expression and activity of several antioxidant enzymes like glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and catalase. Together, these results suggest the potential role of S. pombe Ras1 in mitigating oxidative stress response.


Assuntos
Schizosaccharomyces , Espécies Reativas de Oxigênio/metabolismo , terc-Butil Hidroperóxido/toxicidade , terc-Butil Hidroperóxido/metabolismo , Schizosaccharomyces/genética , Schizosaccharomyces/metabolismo , Antimicina A/farmacologia , Antimicina A/metabolismo , Estresse Oxidativo , Oxirredução
4.
Mymensingh Med J ; 32(2): 550-555, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37002770

RESUMO

The present invitro type of study has done to check the effect of blood contamination & chlorhexidine combination on the bond strength of brackets bonded with self-etch primer technique. The study consisted of ninety sound human upper premolars (extracted for orthodontic purpose) fixed in a self-cure acrylic block and segregated into three groups of 30 samples each. 0.022 slot metal MBT brackets (Gemini series-3M unitek) were bonded with self-etch primer using Transbond XT composite, CA, USA and light cure for 40 seconds) on clean buccal surface. Teeth were divided into 3 groups-Group A/Control group, Group B, Group C. A computer was used to record the force applied to debond the bonded bracket in the unit of Newton. The analysis of variance indicated that there were significant differences (F value = 6.891, p value=0.002) in bond strengths between the various groups tested. The highest value of shear bond strength occurred when chlorhexidine (Group C) was used to remove the blood contamination (mean=15.874 MPa). When bonding was done in ideal condition (Group A), shear bond strength obtained was slightly lower (mean=14.497 MPa) as compared to Group C. On the other hand, lowest shear bond strength among all three groups occurred when blood contamination (Group B) was removed with water (mean=11.059 MPa). Analysis of the study showed that shear bond strength of orthodontic brackets to enamel significantly decreased during bonding with self-etch primer in blood contamination condition. Self-etch primer displayed considerably superior performance with the use of chlorhexidine instead of water to wash the blood contamination.


Assuntos
Clorexidina , Braquetes Ortodônticos , Humanos , Clorexidina/farmacologia , Condicionamento Ácido do Dente/métodos , Teste de Materiais , Resistência ao Cisalhamento
5.
J Foot Ankle Res ; 16(1): 13, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36922851

RESUMO

BACKGROUND: In adults with diabetes, diabetic foot ulcer (DFU) and amputation are common and associated with significant morbidity and mortality. PURPOSE: Identify tools predicting risk of DFU or amputation that are prognostically accurate and clinically feasible. METHODS: We searched for systematic reviews (SRs) of tools predicting DFU or amputation published in multiple databases from initiation to January, 2023. We assessed risk of bias (ROB) and provided a narrative review of reviews describing performance characteristics (calibration and discrimination) of prognostically accurate tools. For such tools, we additionally reviewed original studies to ascertain clinical applicability and usability (variables included, score calculation, and risk categorization). RESULTS: We identified 3 eligible SRs predicting DFU or amputation risk. Two recent SRs (2020 and 2021) were rated as moderate and low ROB respectively. Four risk prediction models - Boyko, Martins-Mendes (simplified), Martins-Mendes (original), and PODUS 2020 had good prognostic accuracy for predicting DFU or amputation over time horizons ranging from 1- to 5-years. PODUS 2020 predicts absolute average risk (e.g., 6% risk of DFU at 2 years) and consists of 3-binary variables with a simple, summative scoring (0-4) making it feasible for clinic use. The other 3 models categorize risk subjectively (e.g., high-risk for DFU at 3 years), include 2-7 variables, and require a calculation device. No data exist to inform rescreening intervals. Furthermore, the effectiveness of targeted interventions in decreasing incidence of DFU or amputation in response to prediction scores is unknown. CONCLUSIONS: In this review of reviews, we identified 4 prognostically accurate models that predict DFU or amputation in persons with diabetes. The PODUS 2020 model, predicting absolute average DFU risk at 2 years, has the most favorable prognostic accuracy and is clinically feasible. Rescreening intervals and effectiveness of intervention based on prediction score are uncertain.


Assuntos
Diabetes Mellitus , Pé Diabético , Úlcera do Pé , Adulto , Humanos , Pé Diabético/epidemiologia , Fatores de Risco , Revisões Sistemáticas como Assunto , Prognóstico , Amputação Cirúrgica
7.
BMC Palliat Care ; 21(1): 153, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36045352

RESUMO

BACKGROUND: The limited access to palliative care resources along with the social stigma around cancer largely explains the poor quality of life (QoL) of Indian advanced cancer patients. As advanced cancer patients with poor QoL often harbour a desire for hastened death (DHD), it is imperative to understand factors affecting DHD, or the desire to live (DTL) among advanced cancer patients in India. We aim to examine the relationship between DTL and physical, psychological, spiritual, and social factors measuring patients' QoL alongside their awareness of their late cancer stage. METHODS: We surveyed 200 patients from a tertiary cancer hospital in India to collect their DTL, awareness of cancer stage, demographic characteristics, and standardized measures for patients' QoL. We used a linear probability regression model to quantify the association between these factors and patients' DTL among the final sample of 192 patients with no missing information for the variables of interest. RESULTS: Among the various domains affecting cancer patients' QoL, we found that the pain severity score (ranging from 0 to 10) and psychological distress score (ranging from 0 to 42) are negatively associated with the DTL. One point increase in each score reduced the DTL by 2.2% (p < 0.05) and 0.7% (p < 0.05), respectively. Our results also showed that patients whose perceived socio-economic status (SES) is poor have a 16% (p < 0.05) lower probability of DTL, compared to those with higher SES (lower middle class, upper middle class, and wealthy). Controlling for caste, religion, gender, age, marital status and years of education, we found psychological distress is statistically higher among patients belonging to this bottom SES. CONCLUSIONS: We found that pain severity, psychological distress and perceived low SES are negatively associated with the desire to live in advanced cancer patients. Future research should focus on developing interventions to improve physical pain and psychological distress, particularly for patients who are socially and economically disadvantaged.


Assuntos
Neoplasias , Qualidade de Vida , Humanos , Índia , Neoplasias/complicações , Neoplasias/psicologia , Dor/psicologia , Cuidados Paliativos/psicologia , Qualidade de Vida/psicologia , Fatores Sociais
8.
Ann Intern Med ; 175(5): 701-709, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35226522

RESUMO

BACKGROUND: Remdesivir is approved for the treatment of adults hospitalized with COVID-19. PURPOSE: To update a living review of remdesivir for adults with COVID-19. DATA SOURCES: Several electronic U.S. Food and Drug Administration, company, and journal websites from 1 January 2020 through 19 October 2021. STUDY SELECTION: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. DATA EXTRACTION: One reviewer abstracted, and a second reviewer verified data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. DATA SYNTHESIS: Since the last update (search date 9 August 2021), 1 new RCT and 1 new subtrial comparing a 10-day course of remdesivir with control (placebo or standard care) were identified. This review summarizes and updates the evidence on the cumulative 5 RCTs and 2 subtrials for this comparison. Our updated results confirm a 10-day course of remdesivir, compared with control, probably results in little to no mortality reduction (5 RCTs). Updated results also confirm that remdesivir probably results in a moderate increase in the proportion of patients recovered by day 29 (4 RCTs) and may reduce time to clinical improvement (2 RCTs) and hospital length of stay (4 RCTs). New RCTs, by increasing the strength of evidence, lead to an updated conclusion that remdesivir probably results in a small reduction in the proportion of patients receiving ventilation or extracorporeal membrane oxygenation at specific follow-up times (4 RCTs). New RCTs also alter the conclusions for harms-remdesivir, compared with control, may lead to a small reduction in serious adverse events but may lead to a small increase in any adverse event. LIMITATION: The RCTs differed in definitions of COVID-19 severity and outcomes reported. CONCLUSION: In hospitalized adults with COVID-19, the findings confirm that remdesivir probably results in little to no difference in mortality and increases the proportion of patients recovered. Remdesivir may reduce time to clinical improvement and may lead to small reductions in serious adverse events but may result in a small increase in any adverse event. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.


Assuntos
Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Tratamento Farmacológico da COVID-19 , Médicos , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Adulto , Alanina/uso terapêutico , Humanos , Estados Unidos
9.
MDM Policy Pract ; 6(2): 23814683211061398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820528

RESUMO

Purpose. We investigated 1) perceived roles in decision-making among advanced cancer patients in 5 Asian countries 2) associations of patient characteristics with these roles, and 3) the association of perceived roles with quality of life and perceived quality of care. Methods. We surveyed 1585 patients with stage IV solid cancer. Multinomial logistic regressions were used to analyze associations of patient characteristics with decision-making roles. Multivariate regressions were used to analyze associations of decision-making roles with quality of life and care. Results. The most common perceived-role was no patient involvement. Most patients (73%) reported roles consistent with their preferences. Being male, nonminority, higher educated, aware of advanced cancer diagnosis, and knowledge of cancer diagnosis for ≥1 year were associated with higher levels of patient involvement in decision-making. Compared to no patient involvement, joint decision-making (together with physicians/family) was associated with higher social (ß = 2.49, P < 0.01) and spiritual (ß = 2.64, P < 0.01) well-being, and better quality of physician communication (ß = 9.73, P < 0.01) and care coordination (ß = 13.96, P < 0.01) while making decisions alone was associated with lower emotional (ß = -1.43, P < 0.01), social (ß = -2.39, P < 0.01), and spiritual (ß = -2.98, P < 0.01) well-being. Conclusions. Findings suggest that a substantial number of advanced cancer patients were not (and preferred not to be) involved in decision-making. Despite this finding, joint decision-making together with physicians/family was associated with better quality of life and care. Implications. Physicians should explain the benefits of shared decision making to patients and encourage participation in decision-making, while ensuring that patients feel supported and do not find decision-making overwhelming.

11.
Cureus ; 13(9): e17774, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34659985

RESUMO

Aspergillus spp. are ubiquitous molds that cause a wide range of clinical syndromes depending on the immune status of the host. Herein, we present a case of a patient with rheumatoid arthritis on long-term immunosuppressive medications, with a persistent dry cough and left-sided chest pain for over a year, who presented with acute sternal drainage. Computed tomography of the chest showed chronic pulmonary abnormalities, parasternal fluid, and bone destruction of the distal sternum and left sixth rib. The patient underwent debridement; sternal biopsy tissue showed septate hyphae with acute-angled branching, and Aspergillus fumigatus grew in culture. We suspected that the patient developed chronic necrotizing pulmonary aspergillosis (CNPA) that traversed tissue planes and caused chest wall osteomyelitis. The patient received voriconazole and surgical debridement, with clinical and radiological improvement. This case demonstrates the importance of considering CNPA as a diagnosis in patients with moderate degrees of immunosuppression and chronic respiratory symptoms, and Aspergillus spp. as an etiology of osteomyelitis in such patients.

13.
Ann Intern Med ; 174(5): 663-672, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33560863

RESUMO

BACKGROUND: Remdesivir is being studied and used for treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To update a previous review of remdesivir for adults with COVID-19, including new meta-analyses of patients with COVID-19 of any severity compared with control. DATA SOURCES: Several sources from 1 January 2020 through 7 December 2020. STUDY SELECTION: English-language, randomized controlled trials (RCTs) of remdesivir for COVID-19. New evidence is incorporated by using living review methods. DATA EXTRACTION: 1 reviewer abstracted data; a second reviewer verified the data. The Cochrane Risk of Bias Tool and GRADE (Grading of Recommendations Assessment, Development and Evaluation) method were used. DATA SYNTHESIS: The update includes 5 RCTs, incorporating data from a new large RCT and the final results of a previous RCT. Compared with control, a 10-day course of remdesivir probably results in little to no reduction in mortality (risk ratio [RR], 0.93 [95% CI, 0.82 to 1.06]; 4 RCTs) but may result in a small reduction in the proportion of patients receiving mechanical ventilation (RR, 0.71 [CI, 0.56 to 0.90]; 3 RCTs). Remdesivir probably results in a moderate increase in the percentage of patients who recovered and a moderate decrease in serious adverse events and may result in a large reduction in time to recovery. Effect on hospital length of stay or percentage remaining hospitalized is mixed. Compared with a 10-day course for those not requiring ventilation at baseline, a 5-day course may reduce mortality, the need for ventilation, and serious adverse events while increasing the percentage of patients who recovered or clinically improved. LIMITATION: Summarizing findings was challenging because of varying disease severity definitions and outcomes. CONCLUSION: In hospitalized adults with COVID-19, remdesivir probably results in little to no mortality difference but probably improves the percentage recovered and reduces serious harms and may result in a small reduction in the proportion receiving ventilation. For patients not receiving ventilation, a 5-day course may provide greater benefits and fewer harms with lower drug costs than a 10-day course. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Pneumonia Viral/tratamento farmacológico , Monofosfato de Adenosina/uso terapêutico , Adulto , Alanina/uso terapêutico , Humanos , Pneumonia Viral/virologia , SARS-CoV-2
14.
J Mater Sci Mater Med ; 32(2): 19, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33576907

RESUMO

Our study aimed at development of Silver, Iron and Gold nanoparticles of Lycopene isolated from tomato by using green synthesis technique and to evaluate its anticancer potential against colorectal and cervical cancer. Lycopene was extracted by benzene extraction method and the silver, iron and gold nanoparticles were developed by green synthesis method. 1% aqueous extract of isolated Lycopene was mixed with 1% solutions of AgNO3, FeCl3 and HAuCl4 solutions and incubated at ambient temperature for 3-4 h separately and observed for the color change which is an indicative of formation of the nanoparticles. The prepared nanoparticles were characterized by FTIR, SEM, XRD analysis and evaluated for their antimicrobial potential. The cytotoxicity studies were carried out by in vitro assay like MTT, SRB and Tryphan blue method against Colo 320 DM, HT 29, and Hella. SEM showed nanosized particles of 50-100 nm range, whereas no antimicrobial activity was exhibited by the prepared nanoparticles. In MTT assay the LyAgNP showed maximum 41.41 ± 0.4124% inhibition against COLO320DM, whereas LyGNP exhibited 41.47 ± 0.4469% inhibition against HT 29 and LyAgNP showed 40.9 ± 0.6908% inhibition against Hella cells. In SRB assay LyAgNP showed maximum 82.68 ± 1.1798% inhibition against COLO320DM, whereas LyGNP exhibited maximum 91.21 ± 0.2372% inhibition against HT29 and 87.98 ± 0.5878% inhibition against Hella cells. In tryphan blue assay against COLO320DM, HT29 and Hella cells, the maximum inhibition exhibited by the prepared nanoparticles were observed as LyGNP 83.45 ± 0.4694%, LyAgNP 88.05 ± 0.1870% and LyAgNP65.47 ± 0.4766%. We conclude that the developed nanoparticles of Lycopene exhibited potential anticancer activity against Colorectal and cervical cancer cell as compared with pure Lycopene.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Licopeno/farmacologia , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Feminino , Ouro/química , Química Verde , Células HT29 , Células HeLa , Humanos , Ferro/química , Licopeno/administração & dosagem , Licopeno/isolamento & purificação , Solanum lycopersicum/química , Nanopartículas Metálicas/administração & dosagem , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Varredura , Nanotecnologia , Prata/química , Espectroscopia de Infravermelho com Transformada de Fourier , Neoplasias do Colo do Útero/tratamento farmacológico , Difração de Raios X
15.
J Physiol Pharmacol ; 72(4)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35072654

RESUMO

The increasing burden of neurological disorders is becoming a worldwide health challenge and researchers are continuously struggling to cure them by utilizing the miraculous medicinal properties of plants. The crude methanolic extract of whole herb of Phyla nodiflora (Pn.Cr) was subjected to phytochemical, antioxidant and neuropharmacological assessment. The Pn.Cr was initially exposed to the in vitro examination for phytocomposition through ultra-high performance liquid chromatography (UHPLC). The Sprague Dawley rats were chronically administered with various doses (100, 200 and 300 mg/kg) of Pn.Cr for one month with subsequent exposure to neurobehavioral and biochemical experimentation. The Pn.Cr exhibited a dose-dependent anxiolytic effect (P < 0.05 in comparison to control) as rats preferred central, illuminated and open arm zones in open field (OFT), light/dark (L/D) and elevated plus maze (EPM) tests. Likewise, scopolamine-induced amnesia was noticeably reversed with P < 0.05 by Pn.Cr as animals showed improved spontaneous alternation, discrimination index and shorter escape latencies in Y-maze, novel object recognition (NOR) and Morris water maze (MWM) tests. Subsequently, in vivo enzymatic assays depicted the reduced acetylcholinesterase and malondialdehyde levels. The levels of oxidative stress combating enzymes (glutathione peroxidase and superoxide dismutase) were increased in a dose-dependent style. The UHPLC detected 22 phytocompounds were further investigated in silico studied to predict the interaction of blood-brain barrier (BBB) crossing phytocompounds with human acetylcholinesterase. The four BBB crossing phytocompounds belonging to flavonoids, chalcones and alkaloids showed possible interaction with the target enzyme. We found that the phytocompounds owned by Pn.Cr might be playing multiple roles in modulation of different pathways to hinder the pathophysiology of neurological disorders including anxiety and Alzheimer's disease.


Assuntos
Acetilcolinesterase , Extratos Vegetais , Acetilcolinesterase/metabolismo , Animais , Antioxidantes , Cromatografia Líquida de Alta Pressão , Aprendizagem em Labirinto , Estresse Oxidativo , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-Dawley
16.
Ann Intern Med ; 174(2): 209-220, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33017170

RESUMO

BACKGROUND: Few treatments exist for coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the effectiveness and harms of remdesivir for COVID-19. DATA SOURCES: Several databases, tables of contents of journals, and U.S. Food and Drug Administration and company websites were searched from 1 January through 31 August 2020. STUDY SELECTION: English-language, randomized trials of remdesivir treatments for adults with suspected or confirmed COVID-19. New evidence will be incorporated using living review methods. DATA EXTRACTION: Single-reviewer abstraction and risk-of-bias assessment verified by a second reviewer; GRADE (Grading of Recommendations Assessment, Development and Evaluation) methods used for certainty-of-evidence assessments. DATA SYNTHESIS: Four randomized trials were included. In adults with severe COVID-19, remdesivir compared with placebo probably improves recovery by a large amount (absolute risk difference [ARD] range, 7% to 10%) and may result in a small reduction in mortality (ARD range, -4% to 1%) and a shorter time to recovery or clinical improvement. Remdesivir may have little to no effect on hospital length of stay. Remdesivir probably reduces serious adverse events by a moderate amount (ARD range, -6% to -8%). Compared with a 10-day remdesivir course, a 5-day course may reduce mortality, increase recovery or clinical improvement by small to moderate amounts, reduce time to recovery, and reduce serious adverse events among hospitalized patients not requiring mechanical ventilation. Recovery due to remdesivir may not vary by age, sex, symptom duration, or disease severity. LIMITATIONS: Low-certainty evidence with few published trials, including 1 preliminary report and 2 open-label trials. Trials excluded pregnant women and adults with severe kidney or liver disease. CONCLUSION: In hospitalized adults with COVID-19, remdesivir probably improves recovery and reduces serious adverse events and may reduce mortality and time to clinical improvement. For adults not receiving mechanical ventilation or extracorporeal membrane oxygenation, a 5-day course of remdesivir may provide similar benefits to and fewer harms than a 10-day course. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs, Veterans Health Administration Office of Research and Development, Health Services Research and Development Service, and Evidence Synthesis Program.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Monofosfato de Adenosina/administração & dosagem , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Alanina/administração & dosagem , Alanina/efeitos adversos , Alanina/uso terapêutico , Antivirais/administração & dosagem , Antivirais/efeitos adversos , Esquema de Medicação , Humanos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , SARS-CoV-2 , Índice de Gravidade de Doença
17.
J Chiropr Educ ; 35(1): 22-27, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31725326

RESUMO

OBJECTIVE: To assess the self-perceived importance, skills, and utilization of evidence-based practice (EBP) among faculty and students at a chiropractic institution without a structured EBP program. The survey also evaluated EBP satisfaction among students and EBP implementation barriers/facilitators among the faculty. METHODS: In this cross-sectional study, a set of organized questionnaires to assess the importance of EBP and self-perceived skills, utilization, barriers, and facilitators for faculty members, and student satisfaction was administered to the students and faculty of a chiropractic institution in February-March 2016. Descriptive statistics were used to evaluate responses. RESULTS: A total of 417 (60.1%) students and 27 (60.0%) faculty members completed the survey. Faculty members' and students' EBP importance values were similar (8.4 and 8.3 out of 10, respectively), but faculty members self-reported their EBP skills (7.3/10) at a higher level than the student self-reported skill level (6.1/10). For utilization, students reported a higher utilization of EBP than that reported by the responding faculty members. Perceived student satisfaction on the quality and content of research-related experiences decreased from the first year to the third (final) year. CONCLUSION: This study found variance in the self-perceived EBP skills, utilization, barriers, and facilitators and that these skills are lagging at our doctor of chiropractic program, which does not have a structured EBP program. Faculty members and students identified the importance for EBP. Similar observations have been found at other chiropractic institutions prior to their implementation of a systematic EBP program. Those developing an EBP curriculum might use these findings to better design, implement, and assess a structured program.

18.
J Physiol Pharmacol ; 71(4)2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33316769

RESUMO

The lithium-pilocarpine model in rats is commonly used to study the characteristic events of acute status epilepticus (SE), epileptogenesis and temporal lobe epilepsy (TLE). Here we investigated the impact of lacosamide alone and in combination with other drugs (pregabalin, piracetam and scopolamine) on spontaneous recurrent seizures (SRSs) and behavioral parameters during the time frame of 6 weeks after SE. In addition, the level of oxidative stress in the hippocampus was accessed by real-time microdialysis study (8-isoprostanes) and antioxidants enzymes in the homogenate. Results revealed severe behavioral deficits with the control epileptic group and animals displayed hyperexcitability, aggression apprehension and memory insufficiency. Pharmacological manipulation for 6 weeks with lacosamide (L) - 80 mg/kg; in polypharmacy with pregabalin (L/P) - 50/50 mg/kg and piracetam (L/Pi) - 50/140 mg/kg significantly (P < 0.05) ameliorated the anxiety-related behavior (open filed, elevated plus maze, light/dark tests), depression (forced swim test) and improved spatial/reference memory (Morris water maze). There were low incidences of seizures in L, L/P and L/Pi groups revealing disease-modifying effects of employed drugs. Furthermore, the chronic use of scopolamine (L/P/S; 50/50/2 mg/kg) as polypharmacy with the concept of antagonizing the cholinergic inputs in the epileptogenic phase aberrated the behavioral situation further worse. Treatments with L/P and L/Pi significantly attenuated (P < 0.05) the oxidative stress by reducing 8-isoprostanes and malondialdehyde (MDA) levels. Furthermore, superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels in the L/P group were significantly (P < 0.05) improved. Overall, our findings support the use of a combination of drugs (L/P and L/Pi) in lithium-pilocarpine model which remarkably ameliorated SRSs, reduced anxiety-related behaviors, retention of spatial/reference memory and lowered oxidative stress in a time-course evaluation 6 weeks post- SE insult.


Assuntos
Anticonvulsivantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Lacosamida/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estado Epiléptico/prevenção & controle , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Quimioterapia Combinada , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Teste de Campo Aberto/efeitos dos fármacos , Pilocarpina , Ratos Sprague-Dawley , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/metabolismo , Estado Epiléptico/psicologia , Natação , Fatores de Tempo
19.
Poult Sci ; 99(8): R4101, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33044919

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The authors retract the above paper due to: 1) conflict of interest among the authors; and 2) addition of coauthor Dr. Muhammad Younus without his knowledge or permission. The authors apologize for these two grave mistakes.

20.
Indian J Anaesth ; 64(6): 488-494, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32792713

RESUMO

BACKGROUND: The aim was to study perioperative management in head and neck cancer, the commonest cancer in Indian men, after radiation therapy. Radiotherapy (RT) targets the tumour and the neck including the thyroid gland. RT induced physical effects (on the airway) and physiological effects (on the thyroid) impact perioperative care. Patients with RT-induced subclinical and mild clinical hypothyroidism are often asymptomatic. Cancer surgery is time-sensitive. Given that parenteral levothyroxine is not available, is a TSH of 15 acceptable for cancer surgery? METHODS: A retrospective study was conducted in a tertiary cancer centre. The records of elective surgery (72 patients) were scrutinised. Data on thyroid profile, airway, treatment of clinical and subclinical hypothyroidism, airway access, recovery and perioperative haemodynamic parameters were retrieved. Correlation of age, sex, RT, chemotherapy with hypothyroidism was done by Chi-square test. The perioperative course was studied. RESULTS: Hypothyroidism (subclinical and clinical) was diagnosed in 39% of patients. All were asymptomatic. There was a significant association between RT and hypothyroidism. In 50% of patients, we encountered a difficult airway. In subclinical hypothyroidism (TSH less than 15), after levothyroxine initiation, the course of anaesthesia, extubation, recovery and postoperative stay was uneventful. CONCLUSIONS: Hypothyroidism and difficult airways are a common sequel of RT. Selected cancer patients with subclinical hypothyroidism had a smooth perioperative course.

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