IMPLEMENTING SYSTEMATIC PATIENT-REPORTED MEASURES FOR CHRONIC CONDITIONS THROUGH THE NAVETA VALUE-BASED TELEMEDICINE INITIATIVE: RESULTS OF AN OBSERVATIONAL, RETROSPECTIVE AND MULTICENTER STUDY.

BACKGROUND: Patient-reported outcome and experience measures can play a critical role in providing patient-centered and value-based healthcare to a growing population of chronically ill patients. Value-based telemedicine platforms such as the Naveta initiative may facilitate the effective integration of these tools into healthcare systems. OBJECTIVE: This study aims to evaluate the response rate to electronic patient-reported outcome measures (ePROMs) and electronic patient-reported experience measures (ePREMs) among patients participating in the Naveta telemedicine initiative, its correlations with sociodemographic and clinical characteristics, and the evolution of the rates over time. METHODS: Between January 1, 2021, and June 30, 2023, a total of 53,364 ePREMs and ePROMs for 20 chronic conditions were administered through the Naveta-Phemium platform. Descriptive statistics were used to summarize continuous and categorical variables. Differences in response rates within each sociodemographic variable were analyzed using logistic regression models, with significance assessed via the chi-square and post-hoc Tukey tests. Two-way ANOVA was used to examine the interaction between time interval and disease type on response rate evolution. RESULTS: A total of 3,372 patients with severe chronic diseases from 64 public hospitals in Spain participated in the Naveta health questionnaire project. The overall response rate to ePROMs and ePREMs during the first 2.5 years of the Naveta initiative was 46.12%, with a baseline rate of 53.33%. Several sociodemographic factors correlated with lower response rates, including male gender, older age, lower education level, frequent alcohol use, being a student, and not being physically active. There were also significant variations in response rates among different types of chronic conditions, with the highest rates for respiratory (71.45%), oncologic (62.70%), digestive (62.40%), and rheumatic diseases (57.82%), and the lowest for HIV+ patients (32.93%). During the first 6 months of follow-up, response rates decreased in all disease types, except for the oncology group, which increased up to 100%. Subsequently, the overall response rate approached baseline levels. CONCLUSIONS: Recognizing the influence of sociodemographic factors on response rates is critical to identifying barriers to participation in telemonitoring programs and ensuring inclusiveness in patient-centered healthcare practices. The observed decline in response rates at follow-up may be due to survey fatigue, highlighting the need for strategies to mitigate this effect. In addition, the variation in response rates across chronic conditions emphasizes the importance of tailoring telemonitoring approaches to specific patient populations.

Postfire biodiversity database for eastern Iberia.

In the summer of 2012, two fires affected Mediterranean ecosystems in the eastern Iberian Peninsula. The size of these fires was at the extreme of the historical variability (megafires). Animals are traditionally assumed to recolonize from source populations outside of the burned area (exogenous regeneration) while plants recover from endogenous regeneration (resprouting and seeding). However, there is increasing evidence of in situ fire survival in animals. To evaluate the effect of large-scale fires on biodiversity and the mechanism of recovery, in 2013, we set up 12 plots per fire, covering burned vegetation at different distances from the fire perimeter and unburned vegetation. In each plot, we followed the postfire recovery of arthropods, reptiles (including some of their parasites), and plants for 2 to 5 years. Here we present the resulting database (POSTDIV) of taxon abundance. POSTDIV totals 19,906 records for 457 arthropod taxa (113,681 individuals), 12 reptile taxa (503 individuals), 4 reptile parasites (234 individuals), and 518 plant taxa (cover-abundance). We provide examples in the R language to query the database.

Recovery course of persistent posterior subretinal fluid after successful repair of rhegmatogenous retinal detachment.

PURPOSE: To investigate best corrected visual acuity (BCVA), subretinal fluid (SRF) absorption time or ellipsoid zone (EZ) restoration time and various variables in patients with persistent SRF after successful primary repair of rhegmatogenous retinal detachment (RRD). METHODS: This retrospective multicenter study allowed independent analysis of the healing pattern by two observers based on composite of serial cross-sectional macular optical coherence tomography (OCT) scans. Univariate and multivariate analyses were implemented. RESULTS: One hundred and three cases had persistent SRF after pars plana vitrectomy, scleral buckling, or pneumatic retinopexy. By univariate analysis, SRF resolution time correlated positively with the number of retinal breaks (p < 0.001) and with increased myopia (p = 0.011). Using multivariate analysis, final BCVA (log MAR) correlated positively with age, duration of RRD, initial BCVA (OR = 3.28; [95%CI = 1.44-7.47]; p = 0.015), and SRF resolution time (OR = 0.46 [95%CI 0.21-1.05]; p = 0.049). EZ restoration time was longer with increasing number of retinal tears (OR = 0.67; [95%CI 0.29-1.52]; p = 0.030), worse final BCVA, and presence of macula-off RRD (OR = 0.26; [95%CI 0.08-0.88]; p = 0.056). SRF resolution time correlated marginally with prone position. CONCLUSIONS: Residual posterior SRF is more common in eyes with multiple breaks or in myopic eyes. Final BCVA is better in younger subjects and in eyes with shorter duration of RRD. Persistent SRF is a self-limited disorder with a mean resolution of 11.2 months with good visual prognosis improving from a mean baseline logMAR of 1.08 to 0.25 at one year.

Astrocytes adjust the dynamic range of cortical network activity to control modality-specific sensory information processing.

Cortical neuron-astrocyte communication in response to peripheral sensory stimulation occurs in a topographic-, frequency-, and intensity-dependent manner. However, the contribution of this functional interaction to the processing of sensory inputs and consequent behavior remains unclear. We investigate the role of astrocytes in sensory information processing at circuit and behavioral levels by monitoring and manipulating astrocytic activity in vivo. We show that astrocytes control the dynamic range of the cortical network activity, optimizing its responsiveness to incoming sensory inputs. The astrocytic modulation of sensory processing contributes to setting the detection threshold for tactile and thermal behavior responses. The mechanism of such astrocytic control is mediated through modulation of inhibitory transmission to adjust the gain and sensitivity of responding networks. These results uncover a role for astrocytes in maintaining the cortical network activity in an optimal range to control behavior associated with specific sensory modalities.

Mitochondrial Reactive Oxygen Species and Lytic Programmed Cell Death in Acute Inflammation.

Significance: Redox signaling through mitochondrial reactive oxygen species (mtROS) has a key role in several mechanisms of regulated cell death (RCD), necroptosis, ferroptosis, pyroptosis, and apoptosis, thereby decisively contributing to inflammatory disorders. The role of mtROS in apoptosis has been extensively addressed, but their involvement in necrotic-like RCD has just started being elucidated, providing novel insights into the pathophysiology of acute inflammation. Recent Advances: p53 together with mtROS drive necroptosis in acute inflammation through downregulation of sulfiredoxin and peroxiredoxin 3. Mitochondrial hydroorotate dehydrogenase is a key redox system in the regulation of ferroptosis. In addition, a noncanonical pathway, which generates mtROS through the Ragulator-Rag complex and acts via mTORC1 to promote gasdermin D oligomerization, triggers pyroptosis. Critical Issues: mtROS trigger positive feedback loops leading to lytic RCD in conjunction with the necrosome, the inflammasome, glutathione depletion, and glutathione peroxidase 4 deficiency. Future Directions: The precise mechanism of membrane rupture in ferroptosis and the contribution of mtROS to ferroptosis in inflammatory disorders are still unclear, which will need further research. Mitochondrial antioxidants may provide promising therapeutic approaches toward acute inflammatory disorders. However, establishing doses and windows of action will be required to optimize their therapeutic potential, and to avoid potential adverse side effects linked to the blockade of beneficial mtROS adaptive signaling. Antioxid. Redox Signal. 39, 708-727.

TREK channels in Mechanotransduction: a Focus on the Cardiovascular System.

Mechano-electric feedback is one of the most important subsystems operating in the cardiovascular system, but the underlying molecular mechanism remains rather unknown. Several proteins have been proposed to explain the molecular mechanism of mechano-transduction. Transient receptor potential (TRP) and Piezo channels appear to be the most important candidates to constitute the molecular mechanism behind of the inward current in response to a mechanical stimulus. However, the inhibitory/regulatory processes involving potassium channels that operate on the cardiac system are less well known. TWIK-Related potassium (TREK) channels have emerged as strong candidates due to their capacity for the regulation of the flow of potassium in response to mechanical stimuli. Current data strongly suggest that TREK channels play a role as mechano-transducers in different components of the cardiovascular system, not only at central (heart) but also at peripheral (vascular) level. In this context, this review summarizes and highlights the main existing evidence connecting this important subfamily of potassium channels with the cardiac mechano-transduction process, discussing molecular and biophysical aspects of such a connection.

Logistic-growth models measuring density feedback are sensitive to population declines, but not fluctuating carrying capacity.

Analysis of long-term trends in abundance of animal populations provides insights into population dynamics. Population growth rates are the emergent interplay of inter alia fertility, survival, and dispersal. However, the density feedbacks operating on some vital rates ("component feedback") can be decoupled from density feedbacks on population growth rates estimated using abundance time series ("ensemble feedback"). Many of the mechanisms responsible for this decoupling are poorly understood, thereby questioning the validity of using logistic-growth models versus vital rates to infer long-term population trends. To examine which conditions lead to decoupling, we simulated age-structured populations of long-lived vertebrates experiencing component density feedbacks on survival. We then quantified how imposed stochasticity in survival rates, density-independent mortality (catastrophes, harvest-like removal of individuals) and variation in carrying capacity modified the ensemble feedback in abundance time series simulated from age-structured populations. The statistical detection of ensemble density feedback from census data was largely unaffected by density-independent processes. Long-term population decline caused from density-independent mortality was the main mechanism decoupling the strength of component versus ensemble density feedbacks. Our study supports the use of simple logistic-growth models to capture long-term population trends, mediated by changes in population abundance, when survival rates are stochastic, carrying capacity fluctuates, and populations experience moderate catastrophic mortality over time.

Viscosity Factor (VF) Complementary to the Statistical Indicators Associated with the Rheological Behavior of Aqueous Solutions of Polyvinyl Alcohol.

The rheological behavior of aqueous solutions of polyvinyl alcohol at 4, 6, 8 and 10% by weight has been studied and evaluated at temperatures of 20, 25, 30 and 35 °C, using five non-Newtonian fluid models independent of time: Ferrys, Robertson-Stiff, Williamson, Sisko, and Ellis de Haven. The classical method consists in carrying out regression analysis. Using a comparative procedure of determination coefficients and variances, the model that most appropriately adjusts the experimental data to said model is selected. From the statistical point of view, the Sisko and Robertson-Stiff models present better regression parameters; to better specify the choice of the respective rheological model, a new factor has been proposed in the literature, the viscosity factor (VF), which expresses the relationship between apparent and dynamic viscosity. The analysis of this factor for the five models confirms the greater stability of the Ellis de Haven model in terms of the coefficient of variation of the VF. The value of VF fluctuates between 1 and 2 for all ranges of temperature and concentration experienced for vinyl alcohol solutions. As a consequence of the above, for the choice of the non-Newtonian fluid model associated with the rheology of the aqueous solution of polyvinyl alcohol, it is necessary to analyze the statistical parameters and the VF factor simultaneously.

Effects of transcranial static magnetic field stimulation over the left dorsolateral prefrontal cortex on random number generation.

OBJECTIVE: Focal application of transcranial static magnetic field stimulation (tSMS) is a neuromodulation technique, with predominantly inhibitory effects when applied to the motor, somatosensory or visual cortex. Whether this approach can also transiently interact with dorsolateral prefrontal cortex (DLPFC) function remains unclear. The suppression of habitual or competitive responses is one of the core executive functions linked to DLPFC function. This study aimed to assess the impact of tSMS on the prefrontal contributions to inhibitory control and response selection by means of a RNG task. METHODS: We applied 20 min of tSMS over the left DLPFC of healthy subjects, using a real/sham cross-over design, during performance of a RNG task. We used an index of randomness calculated with the measures of entropy and correlation to assess the impact of stimulation on DLPFC function. RESULTS: The randomness index of the sequences generated during the tSMS intervention was significantly higher compared to those produced in the sham condition. CONCLUSIONS: Our results indicate that application of tSMS transiently modulates specific functional brain networks in DLPFC, which indicate a potential use of tSMS for treatment of neuropsychiatric disorders. SIGNIFICANCE: This study provides evidence for the capacity of tSMS for modulating DLPFC function.

M-shaped Genioplasty: New Findings after 10 Years of Experience.

This study aimed to evaluate changes of the M-shaped genioplasty in sagittal and vertical planes in a group of 34 patients and describe other indications, such as the increase of the mentolabial angle, decrease in the depth of the mentolabial fold, and the centering of the chin. Methods: A retrospective analysis was performed on 34 patients between 2010 and 2019. All studies were conducted at T0 (preoperative), T1 (a month after surgery), and T2 (1 year after surgery). The position of the bone pogonion (Pg) was measured vertically and horizontally at T0, T1, and T2; the mentolabial angle and the depth of the mentolabial fold were measured at T0 and T2. Results: The average sagittal advancement at T1 was 6.6 mm and at T2 was 6.4 mm. The inferior movement was an average of 5.6 mm at T1 and T2, showing both movements excellent stability. The mentolabial angle increased at T2 an average of 28.2 degrees (5 degrees per each millimeter of inferior movement), whereas the depth of the mentolabial fold decreased an average of 2.8 mm (decreased 49% from the initial depth and decreased 0.56 mm per each mm of inferior movement). The average increase of the lower third of the face was 5 mm. No complications were observed in any patient. Conclusions: M-shaped genioplasty is an anterior osteotomy of the mandible, which allows the chin to move forward and downward. Additionally, it allows an increase of the mentolabial angle and decreases the mentolabial fold.

N-Acetylcysteine normalizes brain oxidative stress and neuroinflammation observed after protracted ethanol abstinence: a preclinical study in long-term ethanol-experienced male rats.

RATIONALE: Using a preclinical model based on the Alcohol Deprivation Effect (ADE), we have reported that N-Acetylcysteine (NAC) can prevent the relapse-like drinking behaviour in long-term ethanol-experienced male rats. OBJECTIVES: To investigate if chronic ethanol intake and protracted abstinence affect several glutamate transporters and whether NAC, administered during the withdrawal period, could restore the ethanol-induced brain potential dysfunctions. Furthermore, the antioxidant and anti-inflammatory effects of NAC during abstinence in rats under the ADE paradigm were also explored. METHODS: The expression of GLT1, GLAST and xCT in nucleus accumbens (Nacc) and dorsal striatum (DS) of male Wistar was analysed after water and chronic ethanol intake. We used the model based on the ADE within another cohort of male Wistar rats. During the fourth abstinence period, rats were treated for 9 days with vehicle or NAC (60, 100 mg/kg; s.c.). The effects of NAC treatment on (i) glutamate transporters expression in the Nacc and DS, (ii) the oxidative status in the hippocampus (Hip) and amygdala (AMG) and (iii) some neuroinflammatory markers in prefrontal cortex (PFC) were tested. RESULTS: NAC chronic administration during protracted abstinence restored oxidative stress markers (GSSG and GGSH/GSH) in the Hip. Furthermore, NAC was able to normalize some neuroinflammation markers in PFC without normalizing the observed downregulation of GLT1 and GLAST in Nacc. CONCLUSIONS: NAC restores brain oxidative stress and neuroinflammation that we previously observed after protracted ethanol abstinence in long-term ethanol-experienced male rats. This NAC effect could be a plausible mechanism for its anti-relapse effect. Also, brain oxidative stress and neuroinflammation could represent and identify plausible targets for searching new anti-relapse pharmacotherapies.

A comprehensive approach to identify challenges for clinical reasoning development in undergraduate dental students and their potential solutions.

INTRODUCTION: Clinical reasoning is a core competence in health professions that impacts the ability to solve patients' health problems. Due to its relevance, it is necessary to identify difficulties arising from different sources that affect clinical reasoning development in students. The aim of this study was to explore a comprehensive approach to identify challenges for clinical reasoning development in undergraduate dental students and their potential solutions. METHODS: Mixed methods were used in four stages: (1) students and clinical teachers focus groups to identify challenges to clinical reasoning development; (2) literature review to explore potential solutions for these challenges; (3) Delphi technique for teacher consensus on pertinence and feasibility of solutions (1-5 scale); and (4) teachers' self-perception of their ability to implement the solutions. RESULTS: Three categories and seven subcategories of challenges were identified: (I) educational context factors influencing the clinical reasoning process; (II) teacher's role in clinical reasoning development; and (III) student factors influencing the clinical reasoning process. From 134 publications identified, 53 were selected for review, resulting in 10 potential solutions. Through two Delphi rounds, teachers rated the potential solutions very highly in terms of relevance (4.50-4.85) and feasibility (3.50-4.29). Finally, a prioritisation ranking of these solutions was generated using their scores for relevance, feasibility, and teachers' self-perception of their ability to implement them. CONCLUSIONS: The present comprehensive approach identified challenges for clinical reasoning development in dental students and their potential solutions, perceived as relevant and feasible by teachers, requiring further research and follow-up actions to address them.

Importance of immunometabolic markers for the classification of patients with major depressive disorder using machine learning.

BACKGROUND: Although there is scientific evidence of the presence of immunometabolic alterations in major depression, not all patients present them. Recent studies point to the association between an inflammatory phenotype and certain clinical symptoms in patients with depression. The objective of our study was to classify major depression disorder patients using supervised learning algorithms or machine learning, based on immunometabolic and oxidative stress biomarkers and lifestyle habits. METHODS: Taking into account a series of inflammatory and oxidative stress biomarkers (C-reactive protein (CRP), tumor necrosis factor (TNF), 4-hydroxynonenal (HNE) and glutathione), metabolic risk markers (blood pressure, waist circumference and glucose, triglyceride and cholesterol levels) and lifestyle habits of the participants (physical activity, smoking and alcohol consumption), a study was carried out using machine learning in a sample of 171 participants, 91 patients with depression (71.42% women, mean age = 50.64) and 80 healthy subjects (67.50% women, mean age = 49.12). The algorithm used was the support vector machine, performing cross validation, by which the subdivision of the sample in training (70%) and test (30%) was carried out in order to estimate the precision of the model. The prediction of belonging to the patient group (MDD patients versus control subjects), melancholic type (melancholic versus non-melancholic patients) or resistant depression group (treatment-resistant versus non-treatment-resistant) was based on the importance of each of the immunometabolic and lifestyle variables. RESULTS: With the application of the algorithm, controls versus patients, such as patients with melancholic symptoms versus non-melancholic symptoms, and resistant versus non-resistant symptoms in the test phase were optimally classified. The variables that showed greater importance, according to the results of the area under the ROC curve, for the discrimination between healthy subjects and patients with depression were current alcohol consumption (AUC = 0.62), TNF-α levels (AUC = 0.61), glutathione redox status (AUC = 0.60) and the performance of both moderate (AUC = 0.59) and vigorous physical exercise (AUC = 0.58). On the other hand, the most important variables for classifying melancholic patients in relation to lifestyle habits were past (AUC = 0.65) and current (AUC = 0.60) tobacco habit, as well as walking routinely (AUC = 0.59) and in relation to immunometabolic markers were the levels of CRP (AUC = 0.62) and glucose (AUC = 0.58). In the analysis of the importance of the variables for the classification of treatment-resistant patients versus non-resistant patients, the systolic blood pressure (SBP) variable was shown to be the most relevant (AUC = 0.67). Other immunometabolic variables were also among the most important such as TNF-α (AUC = 0.65) and waist circumference (AUC = 0.64). In this case, sex (AUC = 0.59) was also relevant along with alcohol (AUC = 0.58) and tobacco (AUC = 0.56) consumption. CONCLUSIONS: The results obtained in our study show that it is possible to predict the diagnosis of depression and its clinical typology from immunometabolic markers and lifestyle habits, using machine learning techniques. The use of this type of methodology could facilitate the identification of patients at risk of presenting depression and could be very useful for managing clinical heterogeneity.

Oxygen Scavenger and Antioxidant LDPE/EVOH/PET-Based Films Containing ß-Carotene Intended for Fried Peanuts (Arachis hypogaea L.) Packaging: Pilot Scale Processing and Validation Studies.

The aim of this study was to develop an oxygen scavenger and antioxidant active packaging material for fried peanuts. The packaging solution, which has been made at the laboratory previously, has been developed by cast film extrusion and is composed of low-density polyethylene-ethylene vinyl alcohol-polyethylene terephthalate (LDPE/EVOH/PET)-based films containing ß-carotene (CAR). In comparison with film without additive, developed film presented an orange colouring (higher L* and b* values and lower a* values) and an increase in oxygen induction time (OIt) from 4.5 to 14.1 min. The incorporation of ß-carotene to the formulation also brings about a significant effect on the thermal stability as maximum degradation temperatures increased around 1%. Regarding the oxygen absorption capacity of the films, values of 1.39 ± 0.10 mL O2 per g of film at laboratory scale and 1.7 ± 0.3 mL O2 per g of multilayer (ML)/LDPE_CAR were obtained, respectively, after 3 days, proving the suitability of the packaging solutions as oxygen absorbers. To validate the packaging solution, the oxidative stability of fried peanuts packed in fabricated multilayer ß-carotene bags was evaluated for 3 months at 40 °C. The hexanal content remained constant during this period. Meanwhile, peanuts packed in ML without ß-carotene increased their hexanal content to 294%. This fact indicated a lower extent of oxidation in fried peanuts compared to food samples packaged in control films, suggesting the potential of ML/LDPE_CAR films as sustainable and antioxidant food packaging systems to offer protection against lipid oxidation in foods. Sensory evaluation confirmed that ML/LDPE_CAR films provided the peanut samples with an extra aroma due to the volatile degradation products of ß-carotene (such as ß-cyclocitral or 6-methyl-5-hepten-2-ol).

p53 drives necroptosis via downregulation of sulfiredoxin and peroxiredoxin 3.

Mitochondrial dysfunction is a key contributor to necroptosis. We have investigated the contribution of p53, sulfiredoxin, and mitochondrial peroxiredoxin 3 to necroptosis in acute pancreatitis. Late during the course of pancreatitis, p53 was localized in mitochondria of pancreatic cells undergoing necroptosis. In mice lacking p53, necroptosis was absent, and levels of PGC-1α, peroxiredoxin 3 and sulfiredoxin were upregulated. During the early stage of pancreatitis, prior to necroptosis, sulfiredoxin was upregulated and localized into mitochondria. In mice lacking sulfiredoxin with pancreatitis, peroxiredoxin 3 was hyperoxidized, p53 localized in mitochondria, and necroptosis occurred faster; which was prevented by Mito-TEMPO. In obese mice, necroptosis occurred in pancreas and adipose tissue. The lack of p53 up-regulated sulfiredoxin and abrogated necroptosis in pancreas and adipose tissue from obese mice. We describe here a positive feedback between mitochondrial H2O2 and p53 that downregulates sulfiredoxin and peroxiredoxin 3 leading to necroptosis in inflammation and obesity.

Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective.

Macrophage polarization refers to the process by which macrophages can produce two distinct functional phenotypes: M1 or M2. The balance between both strongly affects the progression of inflammatory disorders. Here, we review how redox signals regulate macrophage polarization and reprogramming during acute inflammation. In M1, macrophages augment NADPH oxidase isoform 2 (NOX2), inducible nitric oxide synthase (iNOS), synaptotagmin-binding cytoplasmic RNA interacting protein (SYNCRIP), and tumor necrosis factor receptor-associated factor 6 increase oxygen and nitrogen reactive species, which triggers inflammatory response, phagocytosis, and cytotoxicity. In M2, macrophages down-regulate NOX2, iNOS, SYNCRIP, and/or up-regulate arginase and superoxide dismutase type 1, counteract oxidative and nitrosative stress, and favor anti-inflammatory and tissue repair responses. M1 and M2 macrophages exhibit different metabolic profiles, which are tightly regulated by redox mechanisms. Oxidative and nitrosative stress sustain the M1 phenotype by activating glycolysis and lipid biosynthesis, but by inhibiting tricarboxylic acid cycle and oxidative phosphorylation. This metabolic profile is reversed in M2 macrophages because of changes in the redox state. Therefore, new therapies based on redox mechanisms have emerged to treat acute inflammation with positive results, which highlights the relevance of redox signaling as a master regulator of macrophage reprogramming.

Effects of Glucagon-like peptide 1 (GLP-1) analogs in the hippocampus.

The glucagon-like peptide-1 (GLP-1) is a pleiotropic hormone very well known for its incretin effect in the glucose-dependent stimulation of insulin secretion. However, GLP-1 is also produced in the brain, and it displays critical roles in neuroprotection by activating the GLP-1 receptor signaling pathways. GLP-1 enhances learning and memory in the hippocampus, promotes neurogenesis, decreases inflammation and apoptosis, modulates reward behavior, and reduces food intake. Its pharmacokinetics have been improved to enhance the peptide's half-life, enhancing exposure and time of action. The GLP-1 agonists are successfully in clinical use for the treatment of type-2 diabetes, obesity, and clinical evaluation for the treatment of neurodegenerative diseases.