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1.
Artigo em Inglês | MEDLINE | ID: mdl-38766821

RESUMO

Neurological disorders present a formidable challenge in healthcare, necessitating the continuous exploration of innovative therapeutic avenues. This review delves into the burgeoning field of natural diterpenoid derivatives and their promising role in addressing neurological disorders. Derived from natural sources, these compounds exhibit a diverse range of pharmacological properties, positioning them as potential agents for treating conditions such as Alzheimer's and Parkinson's disease. The review highlights recent advancements, shedding light on the multifaceted mechanisms through which diterpenoid derivatives exert their effects, from antiinflammatory to neuroprotective actions. As the scientific community navigates the translational journey from bench to bedside, integrating these natural compounds into neurotherapeutics emerges as a compelling prospect. This exploration of the therapeutic frontiers of natural diterpenoid derivatives signifies a significant step towards innovative and effective strategies in the management of neurological disorders. It highlights the potential of natural compounds to revolutionize neurotherapeutics.

2.
Ageing Res Rev ; 98: 102321, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38723752

RESUMO

Over the last three decades, neurodegenerative diseases (NDs) have increased in frequency. About 15% of the world's population suffers from NDs in some capacity, which causes cognitive and physical impairment. Neurodegenerative diseases, including Amyotrophic Lateral Sclerosis, Parkinson's disease, Alzheimer's disease, and others represent a significant and growing global health challenge. Neuroinflammation is recognized to be related to all NDs, even though NDs are caused by a complex mix of genetic, environmental, and lifestyle factors. Numerous genes and pathways such as NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6. In AD, the binding of Aß with CD36, TLR4, and TLR6 receptors results in activation of microglia which start to produce proinflammatory cytokines and chemokines. Consequently, the pro-inflammatory cytokines worsen and spread neuroinflammation, causing the deterioration of healthy neurons and the impairment of brain functions. Gene therapy has emerged as a promising therapeutic approach to modulate the inflammatory response in NDs, offering potential neuroprotective effects and disease-modifying benefits. This review article focuses on recent advances in gene therapy strategies targeting neuroinflammation pathways in NDs. We discussed the molecular pathways involved in neuroinflammation, highlighted key genes and proteins implicated in these processes, and reviewed the latest preclinical and clinical studies utilizing gene therapy to modulate neuroinflammatory responses. Additionally, this review addressed the prospects and challenges in translating gene therapy approaches into effective treatments for NDs.

3.
Chem Biodivers ; : e202400747, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808441

RESUMO

Phyllanthus emblica L., or Amla, is known for its therapeutic properties and has been used as a medicinal plant. It is rich in vitamin C and other bioactive phytochemicals like polyphenols, gallic acid, chebulagic acid, leutolin, quercetin, etc. Different parts of this plant are used to treat various viral, bacterial, and fungal diseases. This review article summarizes the recent literature relevant to the antiviral, antibacterial, and antifungal effects of P. emblica. A variety of bacteria (Staphylococcus aureus, Bacillus subtillus, Enterococcus faecalis, Salmonella typhi, and Escherichia, etc.), fungi (Alternaria alternate Botroyodiplodia theobromae, Colletotrichum corcori, Curvularia lunata, Fusarium exquisite, Fusarium solanii, Aspergillus niger, Candida albicans, Colletotrichum gleosparoitis, and Macrophomina phaseolina) and viruses, like  Influenza A virus strain H3N2, hepatitis B, Human Immunodeficiency virus type-1 (HIV-1), Simplex virus type 1 (HSV-1) and type 2 (HSV-2) have experimented. Different techniques were used based on the way of identification. `For example, disc diffusion, dilution methods, sound diffusion, Immuno-peroxidase monolayer assay, serum HBV and HBsAg assay, enzyme immunoassay, etc. The present review analyzed and summarized the antimicrobial activities of P. emblica and possible mechanisms of action to provide future directions in translating these findings clinically.

4.
J Neurol Phys Ther ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38709008

RESUMO

BACKGROUND AND PURPOSE: Sport-specific training may improve postural control, while repetitive head acceleration events (RHAEs) may compromise it. Understanding the neural mechanisms underlying postural control may contextualize changes due to training and RHAE. The goal of this study was to determine whether postural sway during the Balance Error Scoring System (BESS) is related to white matter organization (WMO) in collegiate athletes. METHODS: Collegiate soccer (N = 33) and non-soccer athletes (N = 44) completed BESS and diffusion tensor imaging. Postural sway during each BESS stance, fractional anisotropy (FA), and mean diffusivity (MD) were extracted for each participant. Partial least squares analyses determined group differences in postural sway and WMO and the relationship between postural sway and WMO in soccer and non-soccer athletes separately. RESULTS: Soccer athletes displayed better performance during BESS 6, with lower FA and higher MD in the medial lemniscus (ML) and inferior cerebellar peduncle (ICP), compared to non-soccer athletes. In soccer athletes, lower sway during BESS 2, 5, and 6 was associated with higher FA and lower MD in the corticospinal tract, ML, and ICP. In non-soccer athletes, lower sway during BESS 2 and 4 was associated with higher FA and lower MD in the ML and ICP. BESS 1 was associated with higher FA, and BESS 3 was associated with lower MD in the same tracts in non-soccer athletes. DISCUSSION AND CONCLUSIONS: Soccer and non-soccer athletes showed unique relationships between sway and WMO, suggesting that sport-specific exposures are partly responsible for changes in neurological structure and accompanying postural control performance and should be considered when evaluating postural control after injury.Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content, available at: http://links.lww.com/JNPT/A472).

5.
Cureus ; 16(3): e55828, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38590499

RESUMO

Background Postcholecystectomy bile duct injury (BDI) is a management challenge with significant morbidity, mortality, and effects on long-term quality of life. Early referral to a specialized hepatobiliary center and appropriate early management are crucial to improving outcomes and overall quality of life. In this retrospective analysis, we examined patients who were managed at our center over the past 10 years and proposed a triage and management algorithm for BDI in acute settings. Methods Patients referred to our center with BDI from January 2011 to December 2020 were reviewed retrospectively. The primary objective of initial management is to control sepsis and minimize BDI-related morbidity and mortality. All the patients were resuscitated with intravenous fluid, antibiotics (preferably culture-based), correction of electrolyte deficiencies, and organ support if required. A triage module and management algorithm were framed based on our experience. All the patients were triaged based on the presence or absence of bile leaks. Each group was further subdivided into red, yellow, and green zones (depending on the presence of sepsis, organ failure, and associated injuries), and the results were analyzed as per the proposed algorithm. Results One hundred twenty-eight patients with acute BDI were referred to us during the study period, and 116 patients had BDI with a bile leak and 12 patients were without a bile leak. Out of bile leak patients, 106 patients (91.38%) had sepsis with or without organ failure (red and yellow zone) and required invasive intervention in the form of PCD insertion (n=99, 85.34%) and/or laparotomy, lavage, and drainage (n=7, 6.03%). Another 10 patients (8.62%) had controlled external biliary fistula (green zone), of which four were managed with antibiotics, four underwent endoscopic retrograde cholangiopancreatography stenting, and only two (1.7%) patients could undergo Roux-en-Y hepaticojejunostomy upfront due to late referral. Among patients with BDI without bile leaks, nine (75%) had cholangitis (red and yellow zones). Out of these, five required PTBD along with antibiotics and four were managed with antibiotics alone. Only three (25%) patients in this group could undergo definitive repair without any restriction on the timing of referral and were sepsis-free at presentation (green zone). A total of nine patients had a vascular injury, and four of them required digital subtraction angiography and coil embolization. There were three (2.34%) mortalities; all were in the red zone of rest and had successful initial management. In total, five patients were managed with early repair in the acute setting, and the rest underwent definitive intervention at subsequent admissions after being converted to green zone patients with initial management. Conclusion The presented categorization, triaging, and management algorithm provides optimum insight to understand the severity, simplify these complex scenarios, expedite the decision-making process, and thus enhance patient outcomes in early acute settings following BDI.

7.
Ann Biomed Eng ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649514

RESUMO

Male lacrosse and female lacrosse have differences in history, rules, and equipment. There is current debate regarding the need for enhanced protective headwear in female lacrosse like that worn by male lacrosse players. To inform this discussion, 17 high school lacrosse players (6 female and 11 male) wore the Stanford Instrumented Mouthguard during 26 competitive games over the 2021 season. Time-windowing and video review were used to remove false-positive recordings and verify head acceleration events (HAEs). The HAE rate in high school female lacrosse (0.21 per athlete exposure and 0.24 per player hour) was approximately 35% lower than the HAE rate in high school male lacrosse (0.33 per athlete exposure and 0.36 per player hour). Previously collected kinematics data from the 2019 high school male and female lacrosse season were combined with the newly collected 2021 kinematics data, which were used to drive a finite element head model and simulate 42 HAEs. Peak linear acceleration (PLA), peak angular velocity (PAV), and 95th percentile maximum principal strain (MPS95) of brain tissue were compared between HAEs in high school female and male lacrosse. Median values for peak kinematics and MPS95 of HAEs in high school female lacrosse (PLA, 22.3 g; PAV, 10.4 rad/s; MPS95, 0.05) were lower than for high school male lacrosse (PLA, 24.2 g; PAV, 15.4 rad/s; MPS95, 0.07), but the differences were not statistically significant. Quantifying a lower HAE rate in high school female lacrosse compared to high school male lacrosse, but similar HAE magnitudes, provides insight into the debate regarding helmets in female lacrosse. However, due to the small sample size, additional video-verified data from instrumented mouthguards are required.

9.
J Neurotrauma ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38323539

RESUMO

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

10.
Plant J ; 118(3): 607-625, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38361340

RESUMO

The conservation of GOLVEN (GLV)/ROOT MERISTEM GROWTH FACTOR (RGF) peptide encoding genes across plant genomes capable of forming roots or root-like structures underscores their potential significance in the terrestrial adaptation of plants. This study investigates the function and role of GOLVEN peptide-coding genes in Medicago truncatula. Five out of fifteen GLV/RGF genes were notably upregulated during nodule organogenesis and were differentially responsive to nitrogen deficiency and auxin treatment. Specifically, the expression of MtGLV9 and MtGLV10 at nodule initiation sites was contingent upon the NODULE INCEPTION transcription factor. Overexpression of these five nodule-induced GLV genes in hairy roots of M. truncatula and application of their synthetic peptide analogues led to a decrease in nodule count by 25-50%. Uniquely, the GOLVEN10 peptide altered the positioning of the first formed lateral root and nodule on the primary root axis, an observation we term 'noduletaxis'; this decreased the length of the lateral organ formation zone on roots. Histological section of roots treated with synthetic GOLVEN10 peptide revealed an increased cell number within the root cortical cell layers without a corresponding increase in cell length, leading to an elongation of the root likely introducing a spatiotemporal delay in organ formation. At the transcription level, the GOLVEN10 peptide suppressed expression of microtubule-related genes and exerted its effects by changing expression of a large subset of Auxin responsive genes. These findings advance our understanding of the molecular mechanisms by which GOLVEN peptides modulate root morphology, nodule ontogeny, and interactions with key transcriptional pathways.


Assuntos
Regulação da Expressão Gênica de Plantas , Medicago truncatula , Proteínas de Plantas , Raízes de Plantas , Nódulos Radiculares de Plantas , Medicago truncatula/genética , Medicago truncatula/crescimento & desenvolvimento , Medicago truncatula/metabolismo , Medicago truncatula/efeitos dos fármacos , Medicago truncatula/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Nódulos Radiculares de Plantas/genética , Nódulos Radiculares de Plantas/crescimento & desenvolvimento , Nódulos Radiculares de Plantas/metabolismo , Nódulos Radiculares de Plantas/efeitos dos fármacos , Ácidos Indolacéticos/metabolismo , Ácidos Indolacéticos/farmacologia , Nodulação/genética , Meristema/genética , Meristema/crescimento & desenvolvimento , Meristema/efeitos dos fármacos , Peptídeos/metabolismo , Peptídeos/genética
11.
Ecol Food Nutr ; 63(2): 40-62, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38282295

RESUMO

The study evaluated the relationship of various dietary and lifestyle factors with vitamin D status and bone health of adults engaged in office jobs. A total of 100 subjects comprising of 50 males and 50 females (with their willingness to participate) in the age group of 30-50 years were purposively selected for the investigation, who were spending 8 hours in the offices. Results showed that most of the subjects had vitamin D deficit with mean serum vitamin D level as 13.2 ng/ml and 68% were osteopenic. Dietary phytates, sedentary lifestyle, higher body mass index were found to have a deleterious impact on vitamin D status. This silent epidemic needs to be addressed with effective public health initiatives, such as raising awareness about the availability of fortified foods, optimum time, and body surface area for sun exposure.


Assuntos
Deficiência de Vitamina D , Masculino , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Incidência , Deficiência de Vitamina D/epidemiologia , Deficiência de Vitamina D/etiologia , Vitamina D , Dieta/efeitos adversos , Vitaminas , Estilo de Vida
12.
J Appl Toxicol ; 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212177

RESUMO

The International Agency for Research on Cancer has classified N-nitrosodiethylamine (NDEA) as a possible carcinogen and mutagenic substances, placing it in category 2A of compounds that are probably harmful to humans. It is found in nature and tobacco smoke, along with its precursors, and is also synthesized endogenously in the human body. The oral or parenteral administration of a minimal quantity of NDEA results in severe liver and kidney organ damage. The NDEA required bioactivation by CYP450 enzyme to form DNA adduct in the alkylation mechanism. Thus, this bioactivation directs oxidative stress and injury to cells due to the higher formation of reactive oxygen species and alters antioxidant system in tissues, whereas free radical scavengers guard the membranes from NDEA-directed injury in many enzymes. This might be one of the reasons in the etiology of cancer that is not limited to a certain target organ but can affect various organs and organ systems. Although there are various possible approaches for the treatment of NDEA-induced cancer, their therapeutic outcomes are still very dismal. However, several precautions were considered to be taken during handling or working with NDEA, as it considered being the best way to lower down the occurrence of NDEA-directed cancers. The present review was designed to enlighten the general guidelines for working with NDEA, possible mechanism, to alter the antioxidant line to cause malignancy in different parts of animal body along with its protective agents. Thus, revelation to constant, unpredictable stress situations even in common life may remarkably augment the toxic potential through the rise in the oxidative stress and damage of DNA.

13.
Indian J Ophthalmol ; 72(3): 391-396, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38099369

RESUMO

PURPOSE: Adherence to glaucoma medical therapy is a key factor in achieving target intraocular pressure to prevent glaucoma progression. To determine factors affecting medication adherence in glaucoma patients in an urban population belonging to poor socioeconomic status. METHODS: A cross-sectional study was conducted on 200 patients attending glaucoma services in a tertiary referral hospital of North India. Adherence to medication was determined subjectively by questionnaire and objectively by counting the number of used bottles at the end of a month or during refill, whichever was earlier. Patient-related parameters in adherence toward glaucoma medication were studied based on demography, knowledge, attitudes, and practices (KAP). The statistical techniques of bivariate and multivariate logistic regression were adopted to test the objective. RESULTS: The population was statistically homogeneous based on gender and income in both groups. A large proportion of patients had bilateral disease (87%) and were on two or more medications (62.5%). Adherence to glaucoma medical therapy was seen in 68% of patients, with knowledge about glaucoma present in 58% of patients. Deterrents to drug adherence were identified as forgetfulness (71%), unavailability of drugs (19%) or funds to purchase the same (26%), polypharmacy (21%), and side effects (5%). Dependence on an escort by 44% and dependence on hospital supply of medications by 60% emerged as the contextual factors requiring scrutiny while prescribing lifelong glaucoma medications. Disease misconceptions (53%) were prevalent and drug instillation practices were unsatisfactory (57%). CONCLUSION: The study offers insight into patients' perspectives regarding the lifetime use of antiglaucoma medications and focuses on key issues linked to drug nonadherence.


Assuntos
Anti-Hipertensivos , Glaucoma , Humanos , Estudos Transversais , Anti-Hipertensivos/uso terapêutico , Glaucoma/tratamento farmacológico , Pressão Intraocular , Tonometria Ocular
14.
J Appl Biomech ; 40(2): 138-146, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38154023

RESUMO

Disruptions in gait function are common after concussion in adolescents; however, the neuromotor control deficits driving these gait disruptions are not well known. Fifteen concussed (age mean [SD]): 17.4 [0.6], 13 females, days since injury: 26.3 [9.9]) and 17 uninjured (age: 18.0 [0.7], 10 females) adolescents completed 3 trials each of single-task gait and dual-task gait (DT). During DT, participants simultaneously walked while completing a serial subtraction task. Gait metrics and variability in instantaneous mean frequency in lower extremity muscles were captured by inertial sensors and surface electromyography, respectively. A 2-way analysis of covariance was used to compare gait metrics across groups and conditions. Functional principal components analysis was used to identify regions of variability in instantaneous mean frequency curves. Functional principal component scores were compared across groups using a Welch statistic. Both groups displayed worse performance on gait metrics during DT condition compared to single-task, with no differences between groups (P < .001). Concussed adolescents displayed significantly greater instantaneous mean frequency, indicated by functional principal component 1, in the tibialis anterior, biceps femoris, and semitendinosus (P < .05) during single-task and DT compared with uninjured adolescents. Our observations suggest that concussed adolescents display inefficient motor unit recruitment lasting longer than 2 weeks following injury, regardless of the addition of a secondary task.


Assuntos
Concussão Encefálica , Marcha , Feminino , Humanos , Adolescente , Marcha/fisiologia , Caminhada/fisiologia , Músculo Esquelético
15.
Sports Med ; 2023 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-38133787

RESUMO

OBJECTIVES: The purpose of this study was to determine sex differences in recovery trajectories of assessments for sport-related concussion using Concussion Assessment, Research and Education (CARE) Consortium data. METHODS: National Collegiate Athletic Association athletes (N = 906; 61% female) from sex-comparable sports completed a pre-season baseline assessment and post-sport-related concussion assessments within 6 h of injury, 24-48 h, when they initiated their return to play progression, when they were cleared for unrestricted return to play, and 6 months post-injury. Assessments included the Standardized Assessment of Concussion, Balance Error Scoring System, Brief Symptom Inventory-18, Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), Sport Concussion Assessment Tool-3 symptom evaluation, Clinical Reaction Time, King-Devick test, Vestibular Ocular Motor Screen, 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale. RESULTS: Only the Vestibular Ocular Motor Screen Total Symptom Score at the 24-48 h timepoint (p = 0.005) was statistically significantly different between sexes. Specifically, female athletes (mean = 60.2, 95% confidence interval [CI] 51.5-70.4) had higher Vestibular Ocular Motor Screen Total Symptom Scores than male athletes (mean = 36.9, 95% CI 27.6-49.3), but this difference resolved by the time of return-to-play initiation (female athletes, mean = 1.8, 95% CI 1.1-2.9; male athletes, mean = 4.1, 95% CI 1.5-10.9). CONCLUSIONS: Sport-related concussion recovery trajectories for most assessments were similar for female and male National Collegiate Athletic Association athletes except for Vestibular Ocular Motor Screen symptoms within 48 h of sport-related concussion, which was greater in female athletes. Female athletes had a greater symptom burden across all timepoints, suggesting that cross-sectional observations may indicate sex differences despite similar recovery trajectories.

16.
Int J Pharm ; 648: 123579, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37931727

RESUMO

The research work aimed to develop a robust sustained release biocompatible brinzolamide (BRZ)-loaded ocular inserts (MeltSerts) using hot-melt extrusion technology with enhanced solubility for glaucoma management. A 32 rotatable central composite design was employed for the optimization of the MeltSerts to achieve sustained release. The effect of two independent factors was examined: Metolose® SR 90SH-100000SR (HPMC, hydroxypropyl methyl cellulose) and Kolliphor® P 407 (Poloxamer 407, P407). The drug release (DR) of BRZ at 0.5 h and 8 h were adopted as dependent responses. The factorial analysis resulted in an optimum composition of 50.00 % w/w of HPMC and 15.00 % w/w of P407 which gave % DR of 9.11 at 0.5 h and 69.10 at 8 h. Furthermore, molecular dynamic simulations were performed to elucidate various interactions between BRZ, and other formulation components and it was observed that BRZ showed maximum interactions with HPC and HPMC with an occupancy of 92.82 and 52.87 %, respectively. Additionally, molecular docking studies were performed to understand the interactions between BRZ and mucoadhesive polymers with ocular mucin (MUC-1). The results indicated a docking score of only -5.368 for BRZ alone, whereas a significantly higher docking score was observed for the optimized Meltserts -6.977, suggesting enhanced retention time of the optimized MeltSerts. SEM images displayed irregular surfaces, while EDS analysis validated uniform BRZ distribution in the optimized formulation. The results of the ocular irritancy studies both ex vivo and in vivo demonstrated that MeltSerts are safe for ocular use. The results indicate that the developed MeltSerts Technology has the potential to manufacture ocular inserts with cost-effectiveness, one-step processability, and enhanced product quality. Nonetheless, it also offers a once-daily regimen, consequently decreasing the dosing frequency, preservative exposure, and ultimately better glaucoma management.


Assuntos
Glaucoma , Simulação de Dinâmica Molecular , Humanos , Preparações de Ação Retardada/uso terapêutico , Simulação de Acoplamento Molecular , Glaucoma/tratamento farmacológico , Solubilidade , Tecnologia
17.
Diabetes Ther ; 14(12): 2109-2125, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801225

RESUMO

INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

18.
Nat Prod Res ; : 1-11, 2023 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-37837421

RESUMO

The present investigation was carried out to characterise bioactive components from G. senegalensis by using Fourier-transform infra-red (FT-IR) spectroscopy, 1H-nuclear magnetic resonance spectroscopy, and gas chromatography-mass spectrometry (GC-MS). The FTIR analysis confirmed the presence of > CH2, -CH3, C = C-C, C-H, C-F, C = C, -C = N-, C-C = N-, and -OH functional groups. The 1H-NMR spectrum revealed the presence of structures of four bioactive compounds i.e. tetratetracontana derivative, ß-carotene, amyrin, and terpineol. GC-MS revealed the presence of different types of high and low molecular weight chemical entities with varying quantities including volatile and essential oil, monoterpenoid, tetraterpenoid, carotenoid, terpenoid, triterpenes, and nortriterpenes. From the results, it could be concluded that G. senegalensis contains various bioactive compounds of biological and pharmacological importance. Overall, this study will provide insight into the characterisation and development of drugs from medicinal plants.

19.
Cancer Drug Resist ; 6(3): 481-498, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37842237

RESUMO

Prostate cancer is the second most prominent form of cancer in men and confers the highest mortality after lung cancer. The term "extracellular vesicles" refers to minute endosomal-derived membrane microvesicles and it was demonstrated that extracellular vesicles affect the environment in which tumors originate. Extracellular vesicles' involvement is also established in the development of drug resistance, angiogenesis, stemness, and radioresistance in various cancers including prostate cancer. Extracellular vesicles influence the general environment, processes, and growth of prostate cancer and can be a potential area that offers a significant lead in prostate cancer therapy. In this review, we have elaborated on the multifaceted role of extracellular vesicles in various processes involved in the development of prostate cancer, and their multitude of applications in the diagnosis and treatment of prostate cancer through the encapsulation of various bioactives.

20.
Clin Biomech (Bristol, Avon) ; 109: 106090, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37696165

RESUMO

BACKGROUND: Gait deficits are common after concussion in adolescents. However, the neurophysiological underpinnings of these gait deficiencies are currently unknown. Thus, the goal of this study was to compare spatiotemporal gait metrics, prefrontal cortical activation, and neural efficiency between concussed adolescents several weeks from injury and uninjured adolescents during a dual-task gait assessment. METHODS: Fifteen concussed (mean age[SD]: 17.4[0.6], 13 female, days since injury: 26.3[9.9]) and 17 uninjured adolescents (18.0[0.7], 10 female) completed a gait assessment with three conditions repeated thrice: single-task walking, single-task subtraction, and dual-task, which involved walking while completing a subtraction task simultaneously. Gait metrics were measured using an inertial sensor system. Prefrontal cortical activation was captured via functional near-infrared spectroscopy. Neural efficiency was calculated by relating gait metrics to prefrontal cortical activity. Differences between groups and conditions were examined, with corrections for multiple comparisons. FINDINGS: There were no significant differences in gait metrics between groups. Compared to uninjured adolescents, concussed adolescents displayed significantly greater prefrontal cortical activation during the single-task subtraction (P = 0.01) and dual-task (P = 0.01) conditions with lower neural efficiency based on cadence (P = 0.02), gait cycle duration (P = 0.03), step duration (P = 0.03), and gait speed (P = 0.04) during the dual-task condition. INTERPRETATION: Our findings suggest that several weeks after injury concussed adolescents demonstrate lower neural efficiency and display a cost to gait performance when cognitive demand is high, e.g., while multitasking, suggesting that the concussed adolescent brain is less able to compensate when attention is divided between two concurrent tasks.


Assuntos
Concussão Encefálica , Marcha , Humanos , Adolescente , Feminino , Recém-Nascido , Marcha/fisiologia , Caminhada/fisiologia , Concussão Encefálica/complicações , Velocidade de Caminhada
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