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1.
Clin Oncol (R Coll Radiol) ; 36(1): e11-e19, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37973477

RESUMO

AIMS: Androgen deprivation therapy (ADT), usually achieved with luteinising hormone releasing hormone analogues (LHRHa), is central to prostate cancer management. LHRHa reduce both testosterone and oestrogen and are associated with significant long-term toxicity. Previous use of oral oestrogens as ADT was curtailed because of cardiovascular toxicity. Transdermal oestrogen (tE2) patches are a potential alternative ADT, supressing testosterone without the associated oestrogen-depletion toxicities (osteoporosis, hot flushes, metabolic abnormalities) and avoiding cardiovascular toxicity, and we here describe their evaluation in men with prostate cancer. MATERIALS AND METHODS: The PATCH (NCT00303784) adaptive trials programme (incorporating recruitment through the STAMPEDE [NCT00268476] platform) is evaluating the safety and efficacy of tE2 patches as ADT for men with prostate cancer. An initial randomised (LHRHa versus tE2) phase II study (n = 251) with cardiovascular toxicity as the primary outcome measure has expanded into a phase III evaluation. Those with locally advanced (M0) or metastatic (M1) prostate cancer are eligible. To reflect changes in both management and prognosis, the PATCH programme is now evaluating these cohorts separately. RESULTS: Recruitment is complete, with 1362 and 1128 in the M0 and M1 cohorts, respectively. Rates of androgen suppression with tE2 were equivalent to LHRHa, with improved metabolic parameters, quality of life and bone health indices (mean absolute change in lumbar spine bone mineral density of -3.0% for LHRHa and +7.9% for tE2 with an estimated difference between arms of 9.3% (95% confidence interval 5.3-13.4). Importantly, rates of cardiovascular events were not significantly different between the two arms and the time to first cardiovascular event did not differ between treatment groups (hazard ratio 1.11, 95% confidence interval 0.80-1.53; P = 0.54). Oncological outcomes are awaited. FUTURE: Efficacy results for the M0 cohort (primary outcome measure metastases-free survival) are expected in the final quarter of 2023. For M1 patients (primary outcome measure - overall survival), analysis using restricted mean survival time is being explored. Allied translational work on longitudinal samples is underway.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/patologia , Estradiol , Antagonistas de Androgênios/uso terapêutico , Androgênios , Qualidade de Vida , Estrogênios , Testosterona
2.
Braz. j. biol ; 84: e253508, 2024. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1360218

RESUMO

Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).


O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).


Assuntos
Animais , Antivirais , Tecido Adiposo , Lagartos , Antibacterianos
3.
Braz. j. biol ; 842024.
Artigo em Inglês | LILACS-Express | LILACS, VETINDEX | ID: biblio-1469369

RESUMO

Abstract Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).


Resumo O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).

4.
Medicine (Baltimore) ; 102(51): e36713, 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38134055

RESUMO

Acute kidney damage (AKI) is a common cause of pediatric intensive care unit (PICU) admissions. Implementing a reno-protective strategy for AKI prediction can significantly enhance outcomes. The renal angina index (RAI) is a risk stratification tool used to predict severe AKI. We aim to assess the reliability and accuracy of the RAI scoring system in predicting AKI as compared to other conventional AKI markers. A prospective, observational study was conducted in the PICU of 2 tertiary medical centers in the Middle East. A total of 446 patients, aged 1-month to 14-years, without chronic kidney disease were enrolled. The RAI was calculated using the renal risk and renal injury score within the first 8 to 12 hours of admission. The accuracy of RAI was compared to changes in serum creatinine from baseline. The outcome was assessed on Day 3 for presence of AKI according to the kidney disease improving global outcome (KDIGO) criteria and associated sequelae. A positive RAI (RA+) was defined as RAI readings ≥ 8. Among the patients, 89 (19.9%) had a positive RAI within the first 8 to 12 hours of admission. The RA + group had a significantly higher occurrence of Day 3 severe AKI (KDIGO stages 2&3) compared to the RA- group (60.6% vs 4.2%, P < .001). The RA + group also had a significantly higher utilization of renal replacement therapy (RRT) (21.3% vs 1.1%, P < .001), longer mean PICU length of stay in days (11.1 ±â€…3.5 vs 5.5 ±â€…2.1, P < .001), and increased mortality (31.4% vs 2.8%, P < .001) compared to the RA- group. The RAI score demonstrated superior predictive ability for Day 3 AKI, with a sensitivity of 72%, specificity of 95%, and area under the curve (AUC) of 0.837, compared to changes in serum creatinine from baseline (sensitivity: 65%, specificity: 89%, AUC: 0.773), fluid overload (sensitivity: 43.7%, specificity: 79%, AUC: 0.613), and illness severity scores (sensitivity: 52.4%, specificity: 80.5%, AUC: 0.657). RAI proved to be a reliable and rapid bedside test for identifying critically ill children at risk of developing severe AKI. This enables physicians to implement reno-protective measures and intervene early, thereby improving prognosis.


Assuntos
Injúria Renal Aguda , Estado Terminal , Criança , Humanos , Creatinina , Estudos Prospectivos , Estado Terminal/terapia , Reprodutibilidade dos Testes , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Injúria Renal Aguda/epidemiologia , Angina Pectoris/complicações
5.
Arthritis Res Ther ; 25(1): 173, 2023 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-37723593

RESUMO

OBJECTIVE: Osteoarthritis (OA) is driven by low-grade inflammation, and controlling local inflammation may offer symptomatic relief. Here, we developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3), where IDO increases the production of local anti-inflammatory metabolites and Gal3 binds carbohydrates to extend IDO's joint residence time. In this study, we evaluated IDO-Gal3's ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA. METHODS: Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT + MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n = 8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3s's ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT + MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n = 7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed. RESULTS: The Gal3 fusion increased joint residence in OA and contralateral knees (p < 0.0001). In OA-affected animals, both saline and IDO-Gal3 improved tactile sensitivity (p = 0.008), but IDO-Gal3 also increased walking velocities (p ≤ 0.033) and improved vertical ground reaction forces (p ≤ 0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p = 0.0025). CONCLUSION: Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.


Assuntos
Galectina 3 , Osteoartrite do Joelho , Masculino , Animais , Ratos , Ratos Endogâmicos Lew , Indolamina-Pirrol 2,3,-Dioxigenase , Interleucina-6 , Inflamação
6.
Heliyon ; 9(7): e18354, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37539214

RESUMO

The oxidation of Carbon monoxide (CO) to Carbon dioxide (CO2) is one of the most extensively investigated reactions in the field of heterogeneous catalysis, and it occurs via molecular rearrangements induced by catalytic metal atoms with oxygen intermediates. CO oxidation and CO2 capture are instrumental processes in the reduction of green-house gas emissions, both of which are used in low-temperature CO oxidation in the catalytic converters of vehicles. CO oxidation and CO2 adsorption at different temperatures are evaluated for palladium-supported silica aerogel (Pd/SiO2). The synthesized catalyst was active and stable for low-temperature CO oxidation. The catalytic activity was enhanced after the first cycle due to the reconditioning of the catalyst's pores. It was found that the presence of oxide forms of palladium in the SiO2 microstructure, influences the performance of the catalysts due to oxygen vacancies that increases the frequency of active sites. CO2 gas adsorption onto Pd/SiO2 was investigated at a wide-ranging temperature from 16 to 120 °C and pressures ∼1 MPa as determined from the isotherms that were evaluated, where CO2 showed the highest equilibrium adsorption capacity at 16 °C. The Langmuir model was employed to study the equilibrium adsorption behavior. Finally, the effect of moisture on CO oxidation and CO2 adsorption was considered to account for usage in real-world applications. Overall, mesoporous Pd/SiO2 aerogel shows potential as a material capable of removing CO from the environment and capturing CO2 at low temperatures.

8.
Eur Rev Med Pharmacol Sci ; 27(10): 4337-4347, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37259714

RESUMO

OBJECTIVE: This study aimed to translate and cross-culturally adapt the Mini-Balance Evaluation Systems Test (Mini-BESTest) to Arabic (Mini-BESTest-Ar) and evaluate its psychometric properties in patients with neurological balance disorders. PATIENTS AND METHODS: The translation and adaptation followed the established guidelines. Validity, internal consistency, test-retest reliability, standard error of measurement (SEM), minimal detectable change (MDC95), and limits of agreement (LOA) were examined in 56 patients. The sensitivity was investigated using the receiver operating characteristic curve. RESULTS: The Mini-BESTest-Ar significantly correlated with the Berg balance scale (BBS) (r = 0.80; p < 0.001) and dynamic gait index (DGI) (rho = 0.75; p < 0.001). All domains showed moderate to very good correlations with BBS (r = 0.62-0.81; p < 0.001) and fair to very good correlations with DGI (rho = 0.4 -0.79; p < 0.05). The internal consistency and test-retest reliability of the total score and all domains were excellent (Cronbach's α = 0.96-0.81, ICC = 0.95-0.81, and r = 0.92-0.68). The SEM, MDC95, and MDC% for total score and domains were 1.19-0.31, 3.29-0.86 points, and 16.5%-66.8% respectively. The LOA revealed no systematic error. A cut-off point of 21.5/28 (Area under the curve = 0.85, sensitivity = 75%, specificity = 75%) was specified. CONCLUSIONS: The Mini-BESTest-Ar has appropriate psychometric properties supporting its usefulness for research and clinical purposes.


Assuntos
Doenças do Sistema Nervoso , Equilíbrio Postural , Humanos , Psicometria , Reprodutibilidade dos Testes , Modalidades de Fisioterapia , Avaliação da Deficiência
9.
Res Sq ; 2023 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-37131836

RESUMO

Objective : Controlling joint inflammation can improve osteoarthritis (OA) symptoms; however, current treatments often fail to provide long-term effects. We have developed an indoleamine 2,3-dioxygenase and galectin-3 fusion protein (IDO-Gal3). IDO converts tryptophan to kynurenines, directing the local environment toward an anti-inflammatory state; Gal3 binds carbohydrates and extends IDO's joint residence time. In this study, we evaluated IDO-Gal3's ability to alter OA-associated inflammation and pain-related behaviors in a rat model of established knee OA. Methods : Joint residence was first evaluated with an analog Gal3 fusion protein (NanoLuc™ and Gal3, NL-Gal3) that produces luminescence from furimazine. OA was induced in male Lewis rats via a medial collateral ligament and medial meniscus transection (MCLT+MMT). At 8 weeks, NL or NL-Gal3 were injected intra-articularly (n=8 per group), and bioluminescence was tracked for 4 weeks. Next, IDO-Gal3's ability to modulate OA pain and inflammation was assessed. Again, OA was induced via MCLT+MMT in male Lewis rats, with IDO-Gal3 or saline injected into OA-affected knees at 8 weeks post-surgery (n=7 per group). Gait and tactile sensitivity were then assessed weekly. At 12 weeks, intra-articular levels of IL6, CCL2, and CTXII were assessed. Results : The Gal3 fusion increased joint residence in OA and contralateral knees (p<0.0001). In OA-affected animals, IDO-Gal3 improved tactile sensitivity (p=0.002), increased walking velocities (p≤0.033), and improved vertical ground reaction forces (p≤0.04). Finally, IDO-Gal3 decreased intra-articular IL6 levels within the OA-affected joint (p=0.0025). Conclusion : Intra-articular IDO-Gal3 delivery provided long-term modulation of joint inflammation and pain-related behaviors in rats with established OA.

10.
Nat Biomed Eng ; 7(9): 1156-1169, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37127708

RESUMO

The treatment of chronic inflammation with systemically administered anti-inflammatory treatments is associated with moderate-to-severe side effects, and the efficacy of locally administered drugs is short-lived. Here we show that inflammation can be locally suppressed by a fusion protein of the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO) and galectin-3 (Gal3). Gal3 anchors IDO to tissue, limiting the diffusion of IDO-Gal3 away from the injection site. In rodent models of endotoxin-induced inflammation, psoriasis, periodontal disease and osteoarthritis, the fusion protein remained in the inflamed tissues and joints for about 1 week after injection, and the amelioration of local inflammation, disease progression and inflammatory pain in the animals were concomitant with homoeostatic preservation of the tissues and with the absence of global immune suppression. IDO-Gal3 may serve as an immunomodulatory enzyme for the control of focal inflammation in other inflammatory conditions.


Assuntos
Galectina 2 , Indolamina-Pirrol 2,3,-Dioxigenase , Animais , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Progressão da Doença
11.
J Contin Educ Health Prof ; 43(4): 247-253, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36988450

RESUMO

INTRODUCTION: People with mental illness are overrepresented in correctional facilities. Correctional officers (COs) lack education to respond to inmates with mental illness. A review was conducted of mental health education programs for COs to identify factors related to effectiveness. METHODS: Medical and criminal justice databases were searched for articles describing mental health education for COs. Studies including measurable outcomes were analyzed using an inductive analytic approach. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for scoping reviews. Data were synthesized using Moore seven levels of outcomes for continuing professional development education. Findings were grouped by curriculum content and described according to levels of outcome. RESULTS: Of 1492 articles, 11 were included in the analysis. Six described mental health programs, two described skill-specific programs, and three described suicide prevention programs. Programs reviewed content about mental illness, practical skills, included didactic and experiential teaching. The programs achieved level 5 on Moore taxonomy. Programs led to improvements in knowledge, skills, and attitudes among officers; however, improvements declined post-training. Officers were receptive to facilitators with correctional or lived mental health experience. Experiential teaching was preferred. Common themes related to programs' effectiveness included applicability to COs, information retention, program facilitators, and teaching methods. DISCUSSION: There is limited, but positive literature suggesting that education programs are beneficial. The decline in improvements suggests need to ensure sustainability of improvements. This review can guide the planning of future education programs for COs based on continuing professional development best practices.


Assuntos
Transtornos Mentais , Saúde Mental , Humanos , Servidores Penitenciários , Transtornos Mentais/terapia , Currículo
12.
Am J Kidney Dis ; 81(1): 25-35.e1, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35750280

RESUMO

RATIONALE & OBJECTIVE: Children with kidney disease and primary hypertension may be more vulnerable to COVID-19. We examined COVID-19 vaccine hesitancy among parents of children with chronic kidney disease or hypertension. STUDY DESIGN: Sequential explanatory mixed-methods design; survey followed by in-depth interviews. SETTING & PARTICIPANTS: Parents of children aged <18 years with kidney disease or primary hypertension within a large pediatric practice. EXPOSURE: Parental attitudes toward general childhood and influenza vaccines assessed by the Vaccine Hesitancy Scale. Kidney disease classification, demographic and socioeconomic factors, experiences with COVID-19, COVID-19 mitigation activities and self-efficacy, and sources of vaccine information. OUTCOME: Willingness to vaccinate child against COVID-19. ANALYTICAL APPROACH: Analysis of variance (ANOVA) test to compare parental attitudes toward general childhood and influenza vaccination with attitudes toward COVID-19 vaccination. Multinomial logistic regression to assess predictors of willingness to vaccinate against COVID-19. Thematic analysis of interview data to characterize influences on parental attitudes. RESULTS: Of the participants, 207 parents completed the survey (39% of approached): 75 (36%) were willing, 80 (39%) unsure, and 52 (25%) unwilling to vaccinate their child against COVID-19. Hesitancy toward general childhood and influenza vaccines was highest among the unwilling group (P < 0.001). More highly educated parents more likely to be willing to vaccinate their children, while Black race was associated with being more likely to be unwilling. Rushed COVID-19 vaccine development as well as fear of serious and unknown long-term side effects were themes that differed across the parental groups that were willing, unsure, or unwilling to vaccinate their children. Although doctors and health care teams are trusted sources of vaccine information, perceptions of benefit versus harm and experiences with doctors differed among these 3 groups. The need for additional information on COVID-19 vaccines was greatest among those unwilling or unsure about vaccinating. LIMITATIONS: Generalizability may be limited. CONCLUSIONS: Two-thirds of parents of children with kidney disease or hypertension were unsure or unwilling to vaccinate their child against COVID-19. Higher hesitancy toward routine childhood and influenza vaccination was associated with hesitancy toward COVID-19 vaccines. Enhanced communication of vaccine information relevant to kidney patients in an accessible manner should be examined as a means to reduce vaccine hesitancy. PLAIN-LANGUAGE SUMMARY: Children with kidney disease or hypertension may do worse with COVID-19. As there are now effective vaccines to protect children from COVID-19, we wanted to find out what parents think about COVID-19 vaccines and what influences their attitudes. We surveyed and then interviewed parents of children who had received a kidney transplant, were receiving maintenance dialysis, had chronic kidney disease, or had hypertension. We found that two-thirds of parents were hesitant to vaccinate their children. Their reasons varied, but the key issues included the need for information pertinent to their child and a consistent message from doctors and other health care providers. These findings may inform an effective vaccine campaign to protect children with kidney disease and hypertension.


Assuntos
COVID-19 , Hipertensão , Vacinas contra Influenza , Influenza Humana , Nefropatias , Criança , Humanos , Vacinas contra COVID-19/uso terapêutico , Intenção , Vacinas contra Influenza/uso terapêutico , COVID-19/epidemiologia , COVID-19/prevenção & controle , Hipertensão/epidemiologia , Atitude , Hipertensão Essencial , Pais , Conhecimentos, Atitudes e Prática em Saúde
13.
Cannabis Cannabinoid Res ; 8(3): 557-566, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35073160

RESUMO

Introduction: There is a growing body of literature supporting the efficacy of cannabis-based medicinal products (CBMPs). Despite an increase in prescribing globally, there is a paucity of high-quality clinical data on the efficacy of CBMPs for many conditions. This study aims to detail the changes in health-related quality of life (HRQoL) and associated clinical safety in patients prescribed CBMPs for any clinical indication from the UK Medical Cannabis Registry (UKMCR). Methods: An uncontrolled prospective case series of the UKMCR was analyzed. Primary outcomes included change from baseline in patient-reported outcome measures collected across all patients (the Generalized Anxiety Disorder Scale [GAD-7], EQ-5D-5L, and Sleep Quality Scale [SQS]) at 1, 3, and 6 months. Secondary outcomes included the self-reported incidence and severity of adverse events. Statistical significance was defined as p<0.050. Results: Three hundred twelve patients were included in the final analysis, with a mean age of 44.8. The most common primary diagnoses were chronic pain of undefined etiology (n=102, 32.7%), neuropathic pain (n=43, 13.8%), and fibromyalgia (n=31, 9.9%). Before enrolment, 112 (35.9%) patients consumed cannabis daily. The median cannabidiol and (-)-trans-Δ9-tetrahydrocannabinol doses prescribed at baseline were 20.0 mg (0.0-510.0 mg) and 3.0 mg (0.0-660.0 mg), respectively. Statistically significant improvements were observed in GAD-7, EQ-5D-5L Index, EQ-5D Visual Analog Scale and SQS scores at 1, 3, and 6 months (p<0.050). There were 94 (30.1%) reported adverse events, of which nausea (n=12, 3.8%), dry mouth (n=10, 3.2%), dizziness (n=7, 2.2%), and somnolence (n=7, 2.2%) were the most common. Conclusion: This study demonstrated CBMP treatment to be associated with a relatively low incidence of severe adverse events in the medium-term. Positive changes following treatment were observed in general, as well as anxiety and sleep-specific, HRQoL outcomes. Randomized controlled trials are still awaited to assess causation; however, real-world evidence can help inform current clinical practice, future trials, and is an important component of pharmacovigilance.


Assuntos
Cannabis , Alucinógenos , Maconha Medicinal , Humanos , Adulto , Maconha Medicinal/efeitos adversos , Qualidade de Vida , Dronabinol/efeitos adversos , Cannabis/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde , Reino Unido/epidemiologia
14.
Mol Syst Des Eng ; 7(1): 44-57, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-35495737

RESUMO

In nature, the precise heterogeneous co-assembly of different protein domains gives rise to supramolecular machines that perform complex functions through the co-integrated activity of the individual protein subunits. A synthetic approach capable of mimicking this process would afford access to supramolecular machines with new or improved functional capabilities. Here we show that the distinct peptide strands of a heterotrimeric α-helical coiled-coil (i.e., peptides "A", "B", and "C") can be used as fusion tags for heterogeneous co-assembly of proteins into supramolecular structures with tunable subunit stoichiometry. In particular, we demonstrate that recombinant fusion of A with NanoLuc luciferase (NL-A), B with superfolder green fluorescent protein (sfGFP-B), and C with mRuby (mRuby-C) enables formation of ternary complexes capable of simultaneously emitting blue, green, and red light via sequential bioluminescence and fluorescence resonance energy transfer (BRET/FRET). Fusion of galectin-3 onto the C-terminus of NL-A, sfGFP-B, and mRuby-C endows the ternary complexes with lactose-binding affinity that can be tuned by varying the number of galectin-3 domains integrated into the complex from one to three, while maintaining BRET/FRET function. The modular nature of the fusion protein design, the precise control of domain stoichiometry, and the multiplicity afforded by the three-stranded coiled-coil scaffold provides access to a greater range of subunit combinations than what is possible with heterodimeric coiled-coils used previously. We envision that access to this expanded range of co-integrated protein domain diversity will be advantageous for future development of designer supramolecular machines for therapeutic, diagnostic, and biotechnology applications.

15.
Ann Biomed Eng ; 50(6): 703-715, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35352215

RESUMO

Altered extracellular matrix (ECM) production is a hallmark of many fibroproliferative diseases, including certain cancers. The high incidence of glycan-rich components within altered ECM makes the use of glycan-binding proteins such as Galectin-3 (G3) a promising therapeutic strategy. The complexity of ECM as a rich 3D network of proteins with varied glycosylation states makes it challenging to determine the retention of glycan-binding proteins in altered ECM environments. Computational models capable of predicting the transport of glycan-binding proteins in altered ECM can benefit the design and testing of such proteins and associated novel therapeutic strategies. However, such computational models require many kinetic parameters that cannot be estimated from traditional 2D pharmacokinetic assays. To validate transport properties of G3 in 3D ECM constructs, we developed a species transport model that includes diffusion and matrix-binding components to predict retention of G3 fusion proteins in glycan-rich ECM. By iteratively comparing our computational model to experimental results, we are able to determine a reasonable range of parameters for a robust computational model of G3 transport. We anticipate this overall approach to building a data-driven model is translatable to other ECM-targeting therapeutic strategies.


Assuntos
Matriz Extracelular , Galectina 3 , Simulação por Computador , Matriz Extracelular/metabolismo , Galectina 3/metabolismo , Glicosilação , Polissacarídeos/metabolismo
16.
Braz J Biol ; 84: e253508, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35195177

RESUMO

Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).


Assuntos
Anti-Infecciosos , Produtos Biológicos/farmacologia , Lagartos , Animais , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus
17.
Int J Radiat Biol ; 98(3): 267-275, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35030065

RESUMO

PURPOSE: This review is focused on radium and radionuclides in its decay chain in honor of Marie Curie, who discovered this element. MATERIALS AND METHODS: We conglomerated current knowledge regarding radium and its history predating our present understanding of this radionuclide. RESULTS: An overview of the properties of radium and its dose assessment is shown followed by discussions about both the negative detrimental and positive therapeutic applications of radium with this history and its evolution reflecting current innovations in medical science. CONCLUSIONS: We hope to remind all those who are interested in the progress of science about the vagaries of the process of scientific discovery. In addition, we raise the interesting question of whether Marie Curie's initial success was in part possible due to her tight alignment with her husband Pierre Curie who pushed the work along.


Assuntos
Radiologia , Rádio (Elemento) , Feminino , França , História do Século XIX , História do Século XX , Humanos , Radiologia/história
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