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Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported. METHODOLOGY: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated. RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment. CONCLUSION: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.
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Adipoquinas , Berberina , Composición Corporal , Gymnema sylvestre , Obesidad , Resistina , Humanos , Masculino , Femenino , Adulto , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Adipoquinas/sangre , Adipoquinas/metabolismo , Composición Corporal/efectos de los fármacos , Persona de Mediana Edad , Berberina/farmacología , Resistina/sangre , Resistina/metabolismo , Apelina , Presión Sanguínea/efectos de los fármacos , Nicotinamida Fosforribosiltransferasa/metabolismo , Citocinas/metabolismo , Citocinas/sangre , Extractos Vegetales/farmacología , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Lectinas , Proteínas Ligadas a GPI/metabolismo , Proteínas Ligadas a GPI/genética , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/uso terapéuticoRESUMEN
BACKGROUND: Obesity is a complex disease for which pharmacotherapy is often used. Anti-obesity drugs (AODs) are characterized by inducing a variable inter-subject body weight reduction (BWR), the attainment of a plateau after their maximal effect is achieved, and weight regain after drug discontinuation, which complicate individualized treatment of obesity. OBJECTIVE: This exploratory analysis aimed to compare the first-month body weight reduction in kg (1mo-BWRkg) and tolerance development (moT) of four known interventions with low (placebo), intermediate (phentermine or mazindol monotherapy), and high (5 active ingredients fixed-dose combination) efficacy, as predictors of their 6-month body weight reduction efficacy in percent (6mo-BWR%). In addition, a detailed analysis of the 6-to-12-month BWR follow-up in subjects under orlistat or diet and exercise regimens was performed. MATERIALS AND METHODS: The analysis included 662 adult subjects with obesity. After the construction of average efficacy and weight rebound curves, subjects were grouped into various 1mo-BWRkg, moT, and 6mo-BWR% intervals, or 6-month body weight rebound parameters for further evaluation. RESULTS: The 6mo-BWR% efficacy level of interventions was confirmed, although a general high intersubject variation was observed. 1mo-BWRkg + moT was found as an acceptable predictor of 6mo-BWR%. Between 50 and 80% of the 6-to-12-month follow-up completers maintained at least 5% BWR%. CONCLUSION: Short-term AODs are useful adjuvants for the 1-year rational treatment of obesity. 1mo-BWRkg + moT is an acceptable parameter to predict the 6mo-BWR% efficacy of these interventions.
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Subjective caregiver burden is highly prevalent in family caregivers. Despite several studies investigating the relationship between subjective caregiver burden and coping strategies, results remain inconsistent. The aim of our study was to systematically review current literature on the relationship between subjective caregiver burden and coping in family carers of dependent adults and older people. A secondary objective was to analyse possible sources of heterogeneity in the estimated effect. The study design was a systematic review with meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) guidelines. We searched several international databases (CINAHL, LILACS, PsycINFO and PubMed) up to February 2024. We performed several subgroup analyses to examine whether study design, methodological quality or care recipient dependency influenced results. Of the 1064 records identified in our search, a total of 80 studies met inclusion criteria. We found a significant association between greater use of dysfunctional coping and higher levels of subjective caregiver burden ( r â¾ $\overline{r}$ = 0.400; 95% CI = 0.315, 0.478); higher use of second-order active coping was significantly associated with lower caregiver burden ( r â¾ $\overline{r}$ = -0.213; 95% CI = -0.316, -0.105). Problem-focused coping showed no statistically significant association with levels of subjective burden; emotion-focused coping was associated with caregiver burden only after controlling for confounding variables ( r â¾ $\overline{r}$ = -0.258; 95% CI = -0.441, -0.055); several individual strategies of this dimension such as acceptance ( r â¾ $\overline{r}$ = -0.135; 95% CI = -0.238, -0.028), positive reappraisal ( r â¾ $\overline{r}$ = -0.178; 95% CI = -0.255, -0.099) and religious coping ( r â¾ $\overline{r}$ = -0.083; 95% CI = -0.162, -0.002), were associated with lower burden. We found that several dimensions of coping strategies are significantly associated with levels of subjective caregiver burden experienced by carers. These results can inform future research evaluating the effectiveness of interventions aimed at improving carers' mental health.
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Adaptación Psicológica , Carga del Cuidador , Cuidadores , Humanos , Carga del Cuidador/psicología , Anciano , Cuidadores/psicologíaRESUMEN
Anxiety symptoms are prevalent in family carers of dependent people. Despite accumulating evidence in the area, there are still inconsistent findings on the association between carer anxiety symptoms and coping strategies. The aim of our study was to systematically analyse the relationship between anxiety symptoms and coping strategies in carers of dependent adults aged 18 years and older, and examine possible sources of heterogeneity in the results. The study design was a systematic review and meta-analysis. We searched several international databases (Pubmed, CINAHL, PsycINFO and LILACS) from June 2022 up to February 2023. We followed the preferred reporting items for systematic reviews and meta-analyses statement and performed several subgroup analyses to examine whether study design, cause of dependency and whether or not controlling for various biases influenced results. Forty-one studies were included in the review. We found significant associations between greater use of dysfunctional coping and higher anxiety symptoms. Greater use of problem-focused coping was associated with lower anxiety symptoms in carers of frail older people, but higher anxiety in carers of people surviving cancer. Emotion-focused coping and some of its individual strategies, such as acceptance and positive reappraisal, in probabilistic samples, were associated with lower anxiety symptoms across all groups. Most of the studies included in this review were cross-sectional. Evidence overall indicates that only specific dimensions and strategies of coping are significantly associated with anxiety symptoms in family carers. These findings should be considered when developing future interventions supporting carers.
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Cuidadores , Demencia , Adulto , Humanos , Adolescente , Anciano , Estrés Psicológico , Depresión/etiología , Ansiedad/etiología , Habilidades de Afrontamiento , Adaptación PsicológicaRESUMEN
Background: Congenital heart disease (CHD) survival rate has improved dramatically due to advances in diagnostic and therapeutic techniques. However, concerning the unrepaired CHD population of moderate and severe complexity, the data regarding risk predictors and surgical outcomes are scarce. Our aim was to describe the surgical results and predictors of in-hospital outcomes in adult patients with moderate-to-severe complexity CHD that were not repaired in childhood. Methods: We conducted a retrospective cohort study that included 49 adult patients with moderate-to-complex CHD who were treated in a single medical centre. Clinical and echocardiographic variables were obtained on admission, after surgical procedures and during follow-up. Results: Most of the patients were female (66%). Left ventricular ejection fraction and right ventricular outflow tract fractional shortening were within the normal range. The median pulmonary artery systolic pressure was 37 (27-55) mm Hg. The median time was 118 (80-181) minutes for extracorporeal circulation and 76 (49-121) minutes for aortic cross-clamping. The most frequent complication was postoperative complete atrioventricular block (12.2%). In-hospital survival rate was 87.7%. The development of low cardiac output syndrome with predominant right ventricle failure in the postoperative period was the most important predictor of in-hospital death (P = 0.03). Conclusions: Deciding to treat adults with CHD is challenging in moderate and severe unrepaired cases. Adequate clinical, functional, and imaging evaluation is essential to determine each patient's suitability for surgical management and to achieve the best clinical outcome for this population.
Contexte: Grâce aux avancées réalisées en matière de techniques diagnostiques et thérapeutiques, la survie des patients atteints d'une cardiopathie congénitale s'est considérablement améliorée. Cependant, en ce qui concerne les personnes atteintes d'une cardiopathie congénitale non corrigée présentant une complexité modérée ou extrême, les données portant sur les facteurs de risque prédictifs ainsi que sur les résultats chirurgicaux sont rares. Notre objectif était de décrire les résultats chirurgicaux ainsi que les facteurs prédictifs des résultats obtenus en milieu hospitalier chez les patients adultes atteints d'une cardiopathie congénitale présentant une complexité modérée ou extrême qui n'a pas été corrigée pendant l'enfance. Méthodologie: Nous avons mené une étude de cohorte rétrospective comprenant 49 patients adultes atteints d'une cardiopathie congénitale modérée ou complexe qui ont reçu leurs traitements dans un seul centre médical. Les variables cliniques et échocardiographiques ont été obtenues au moment de l'admission, après les interventions chirurgicales et pendant la période de suivi. Résultats: Les patients étaient en majorité des femmes (66 %). La fraction d'éjection du ventricule gauche ainsi que la fraction de raccourcissement de la voie d'éjection ventriculaire droite sont demeurées dans les limites de la normale. La pression systolique médiane de l'artère pulmonaire a été de 37 mmHg (27-55 mmHg). Le temps médian écoulé pour la circulation extracorporelle a été de 118 minutes (80-181 minutes) et pour le clampage de la crosse aortique, de 76 minutes (49-121 minutes). Le bloc auriculo-ventriculaire postopératoire complet a été la complication la plus fréquente (12,2 %). Le taux de survie en milieu hospitalier a été de 87,7 %. Le développement du syndrome du faible débit cardiaque accompagné d'une insuffisance prédominante du ventricule droit durant la période postopératoire a constitué le principal facteur prédictif de décès à l'hôpital (p = 0,03). Conclusion: Il est difficile de traiter les adultes qui présentent une cardiopathie congénitale modérée ou sévère non corrigée. Il est essentiel que les évaluations cliniques, fonctionnelles et par imagerie soient réalisées de façon adéquate pour déterminer si une prise en charge chirurgicale convient aux patients et pour garantir les meilleurs résultats cliniques chez ces derniers.
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Cecilia Fernández Del Valle-Laisequilla, Cristian Trejo-Jasso, Juan Carlos Huerta-Cruz, Lina Marcela Barranco-Garduño, Juan Rodríguez-Silverio, Héctor Isaac Rocha-González, Juan Gerardo Reyes-García. Efficacy and safety of a fixed-dose combination of D-norpseudoephedrine, triiodothyronine, atropine, aloin, and diazepam in obese patients. Int J Clin Pharmacol Ther. 2018; 56: 531-538. doi: 10.5414/CP203292. Note from the authors: We realized only now that the affiliation of Cecilia Fernández Del Valle-Laisequilla was indicated in the title page, but due to an unintentional mistake in the final version, the affiliation was not declared in the conflict of interest section, which should read: "Cecilia Fernández Del Valle-Laisequilla is Medical Director of Productos Medix S.A. de C.V."
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Bacteriophages are the most abundant biological entity on the planet, having pivotal roles in bacterial ecology, animal and plant health, and in the biogeochemical cycles. Although, in principle, phages are simple entities that replicate at the expense of their bacterial hosts, due the importance of bacteria in all aspects of nature, they have the potential to influence and modify diverse processes, either in subtle or profound ways. Traditionally, the main application of bacteriophages is phage therapy, which is their utilization to combat and help to clear bacterial infections, from enteric diseases, to skin infections, chronic infections, sepsis, etc. Nevertheless, phages can also be potentially used for several other tasks, including food preservation, disinfection of surfaces, treatment of several dysbioses, and modulation of microbiomes. Phages may also be used as tools for the treatment of non-bacterial infections and pest control in agriculture; moreover, they can be used to decrease bacterial virulence and antibiotic resistance and even to combat global warming. In this review manuscript we discuss these possible applications and promote their implementation.
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Infecciones Bacterianas , Bacteriófagos , Terapia de Fagos , Animales , Bacterias , Infecciones Bacterianas/terapiaRESUMEN
The purpose of this study was to assess the efficacy of a combined training program (CTP) in reducing the effects of dual tasking on the temporal parameters and kinematics of gait, as compared with single-task gait. A controlled, randomized, intervention study was performed in an intervention group and a control group. The intervention group attended three weekly CTP sessions for 24 weeks. Gait pattern was evaluated prior to the baseline intervention, at 12 weeks, and at 24 weeks (Repost). The sample was composed of 22 subjects diagnosed with multiple sclerosis with an Expanded Disability Status Scale score of 0-5.5. A total of 12 patients were allocated to the intervention group and another 10 to the control group. A three-dimensional photogrammetry scanner was connected to a selective attention system designed to present a dual-task gait condition. Dual tasking had an impact on all spatiotemporal parameters of gait, and the most remarkable effect of dual tasking was on double-support time, which increased by 9% with respect to normal walking. In contrast, dual tasking had a trivial effect on single-support time. The CTP was effective in reducing the effects of dual tasking on stride length and velocity of the center of mass after Repost of training (p < .05). The CTP reduced time in double-support phase, whereas single-support time increased after Repost of intervention. The application of the CTP had no effect on the cost of the double task after 12 weeks of intervention. It is suggested to increase the application time over Repost.
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Esclerosis Múltiple , Humanos , Caminata , Marcha , Atención , CogniciónRESUMEN
Being a family carer is associated with increased risk of experiencing depressive symptoms. Despite many decades of research investigating the association between coping strategies and depressive symptoms in carers results across studies remain contradictory. The objective of this study was to systematically review evidence on the association between depressive symptoms and coping strategies in carers of dependent people aged 18 and over and investigate potential sources of heterogeneity of findings. The study design was a systematic review and meta-analysis. We searched Pubmed, CINAHL, PsycINFO and LILACS up to April 2021. We performed meta-analyses following the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement and several subgroup analyses to investigate whether cause of caring dependency, study design, and controlling for several biases influenced results. Fifty-nine studies met our inclusion criteria. We found a robust and statistically significant association between greater use of dysfunctional coping and higher depressive symptoms. Greater use of emotion-focussed coping was associated with fewer depressive symptoms only in studies controlling for confounding bias. Use of problem-focussed coping was related to fewer depressive symptoms in carers of frail older people. The combined use of both problem-focussed and emotion-focussed coping was associated with lower symptoms of depression. Our review concludes that the broad domain of dysfunctional coping is consistently associated with higher levels of depressive symptoms in carers. After controlling for confounders, emotion-focussed coping and several of its individual strategies were consistently associated with fewer depressive symptoms. Whilst problem-focussed coping and some of its individual strategies are also associated with lower depressive symptoms, these strategies may not be as helpful in all caregiving groups.
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Cuidadores , Depresión , Humanos , Adulto , Adolescente , Anciano , Depresión/etiología , Estrés Psicológico , Adaptación Psicológica , EmocionesRESUMEN
Background: Bacteriophage therapy is becoming part of mainstream Western medicine since antibiotics of clinical use tend to fail. It involves applying lytic bacteriophages that self-replicate and induce cell lysis, thus killing their hosts. Nevertheless, bacterial killing promotes the selection of resistant clones which sometimes may exhibit a decrease in bacterial virulence or antibiotic resistance. Methods: In this work, we studied the Pseudomonas aeruginosa lytic phage φDCL-PA6 and its variant φDCL-PA6α. Additionally, we characterized and evaluated the production of virulence factors and the virulence in a Galleria mellonella model of resistant mutants against each phage for PA14 and two clinical strains. Results: Phage φDCL-PA6α differs from the original by only two amino acids: one in the baseplate wedge subunit and another in the tail fiber protein. According to genomic data and cross-resistance experiments, these changes may promote the change of the phage receptor from the O-antigen to the core lipopolysaccharide. Interestingly, the host range of the two phages differs as determined against the Pseudomonas aeruginosa reference strains PA14 and PAO1 and against nine multidrug-resistant isolates from ventilator associated pneumonia. Conclusions: We show as well that phage resistance impacts virulence factor production. Specifically, phage resistance led to decreased biofilm formation, swarming, and type III secretion; therefore, the virulence towards Galleria mellonella was dramatically attenuated. Furthermore, antibiotic resistance decreased for one clinical strain. Our study highlights important potential advantages of phage therapy's evolutionary impact that may be exploited to generate robust therapy schemes.
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Bacteriófagos , Mariposas Nocturnas , Terapia de Fagos , Fagos Pseudomonas , Animales , Virulencia , Pseudomonas aeruginosa , Fagos Pseudomonas/genética , Factores de Virulencia/genética , Farmacorresistencia Microbiana , Antibacterianos/farmacologíaRESUMEN
The gangliosidoses GM2 are a group of pathologies mainly affecting the central nervous system due to the impaired GM2 ganglioside degradation inside the lysosome. Under physiological conditions, GM2 ganglioside is catabolized by the ß-hexosaminidase A in a GM2 activator protein-dependent mechanism. In contrast, uncharged substrates such as globosides and some glycosaminoglycans can be hydrolyzed by the ß-hexosaminidase B. Monogenic mutations on HEXA, HEXB, or GM2A genes arise in the Tay-Sachs (TSD), Sandhoff (SD), and AB variant diseases, respectively. In this work, we validated a CRISPR/Cas9-based gene editing strategy that relies on a Cas9 nickase (nCas9) as a potential approach for treating GM2 gangliosidoses using in vitro models for TSD and SD. The nCas9 contains a mutation in the catalytic RuvC domain but maintains the active HNH domain, which reduces potential off-target effects. Liposomes (LPs)- and novel magnetoliposomes (MLPs)-based vectors were used to deliver the CRISPR/nCas9 system. When LPs were used as a vector, positive outcomes were observed for the ß-hexosaminidase activity, glycosaminoglycans levels, lysosome mass, and oxidative stress. In the case of MLPs, a high cytocompatibility and transfection ratio was observed, with a slight increase in the ß-hexosaminidase activity and significant oxidative stress recovery in both TSD and SD cells. These results show the remarkable potential of CRISPR/nCas9 as a new alternative for treating GM2 gangliosidoses, as well as the superior performance of non-viral vectors in enhancing the potency of this therapeutic approach.
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Gangliosidosis GM2 , Enfermedad de Tay-Sachs , Desoxirribonucleasa I/metabolismo , Fibroblastos/metabolismo , Proteína Activadora de G (M2) , Gangliósido G(M2)/genética , Gangliósido G(M2)/metabolismo , Gangliosidosis GM2/genética , Gangliosidosis GM2/metabolismo , Gangliosidosis GM2/terapia , Edición Génica , Globósidos/metabolismo , Glicosaminoglicanos/metabolismo , Hexosaminidasa A/metabolismo , Humanos , Lipopolisacáridos/metabolismo , Liposomas/metabolismo , Enfermedad de Tay-Sachs/genética , Enfermedad de Tay-Sachs/metabolismo , Enfermedad de Tay-Sachs/terapia , beta-N-Acetilhexosaminidasas/metabolismoRESUMEN
The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug's biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.
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BACKGROUND: Dementia is a priority public health issue due to its high prevalence worldwide and its economic, social, and health impact. However, there are few reports in Mexico based on formal tests and with a clinical approach based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5). OBJECTIVE: This study estimates the prevalence of the main types of dementia among elderly people living in the community in Mexico City. METHODS: A population-based, two-step study was conducted, including 6,204 elderly individuals aged 60 or above with in-home assessment. All participants were screened for cognitive impairment; those who presented some cognitive problem underwent a standardized neurological examination. Each diagnosis was based on the criteria for dementia in the DSM-5, and the final consensus diagnosis of dementia was determined by an expert panel. RESULTS: The global estimated prevalence of dementia in the Mexican population was 7.8% met the criteria for Alzheimer's disease, 4.3% for vascular dementia, and 2.1% for mixed dementia. The prevalence of dementia was higher in women than in men (15.3% versus 12.5%, respectively). CONCLUSION: These results provide evidence to propose strategies for Latin American countries where dementia represents a challenge due to the heterogeneity of the populations and socioeconomic disparities, requiring early diagnosis and at the first levels of care.
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Enfermedad de Alzheimer , Demencia , Anciano , Envejecimiento , Enfermedad de Alzheimer/diagnóstico , Demencia/diagnóstico , Demencia/epidemiología , Demencia/psicología , Femenino , Humanos , Masculino , México/epidemiología , PrevalenciaRESUMEN
OBJECTIVE: Obesity is the strongest risk factor for type 2 diabetes (T2D). We aimed to explore 7% weight reduction rates of mazindol alone or combined with metformin in non-diabetic obese Mexican subjects who had additional risk factors for T2D. MATERIALS AND METHODS: In this randomized double-blind study, 137 participants received 1 mg mazindol (n = 65) alone or combined with 500 mg metformin (n = 72), twice a day, for 6 months. RESULTS: Mazindol and mazindol-metformin were similarly effective. However, when subjects were subclassified into non-diabetics and prediabetics, according to glycated hemoglobin (HbA1c) - < 5.7% and 5.7 - 6.4%, respectively - and/or fasting plasma glucose (FPG) - < 100 mg/dL and 100 - 125 mg/dL, respectively -, differences were evident. Prediabetics in the mazindol-metformin group had a higher rate of 7% weight reduction (78.4%, n = 37) compared to prediabetics treated with mazindol (48.3%, n = 29). Furthermore, mazindol-metformin treatment induced significant reductions in fasting plasma insulin, HOMA-IR, and HbA1c in prediabetics compared to mazindol. No differences were found in any parameter between non-diabetics treated with mazindol (n = 36) and mazindol-metformin (n = 35). CONCLUSION: Our results highlight the effectiveness of mazindol-metformin to achieve higher rates of 7% weight reduction and to improve the glycemic profile in prediabetic obese subjects, which could be useful to prevent or delay T2D in these subjects.
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Diabetes Mellitus Tipo 2 , Metformina , Estado Prediabético , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Método Doble Ciego , Hemoglobina Glucada/análisis , Humanos , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Mazindol , Metformina/farmacología , Metformina/uso terapéutico , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Estado Prediabético/inducido químicamente , Estado Prediabético/tratamiento farmacológico , Pérdida de PesoRESUMEN
The weight loss response to anti-obesity drugs is highly variable and poorly understood, which does not allow us to know, in advance, in which subjects the drug will be effective and in which it will not. The objective of this study was to explore the body weight reduction in kilograms in the first month (1mo-BWRkg) and the development of tolerance as predictors of 6-month efficacy for treatment with 1 mg mazindol twice a day. One hundred ninety-six obese subjects were individually or jointly analyzed. Approximately 60% of subjects developed tolerance to mazindol and achieved increasing proportional levels of 6-month efficacy according to 1mo-BWRkg intervals (<1 kg, 1 to <2 kg, 2 to <4 kg and ≥4 kg). Both moT and 1mo-BWRkg were significantly correlated with the mean percentage body weight reduction (BWR%) after 6-months of treatment. The qualitative analysis of both predictors on the progressive efficacy of mazindol was used to classify patients according to expected efficacy (inefficient, slightly effective, partially effective, or fully effective), based on the mean percentage efficacy and the number of subjects reaching a BWR% of <5%, 5 to <10%, 10 to <15% or ≥15%. In conclusion, combined 1mo-BWRkg and moT were early predictors for the progressive efficacy of 6-month mazindol anti-obesity therapy. This finding represents progress in predictive, preventive, and personalized medicine which could serve for estimating the expectations of individual efficacy with the use of the drug. and highlights the basic principle of personalized medicine, "one size does not fit all".
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Leptin is a cytokine-like hormone that functions as a link between obesity and breast cancer (BC). Leptin treatment induces Epithelial to Mesenchymal Transition (EMT) in BC cell lines. In non-tumoral breast epithelial MCF10A cells, acute leptin treatment induces partial EMT. However, the effect of chronic leptin treatment on EMT in non-tumorigenic breast cells has not been fully explored. This study aimed to evaluate the effect of chronic leptin treatment on the induction of EMT in MCF10A cells. We found that chronic leptin treatment induces a switch from an epithelial to a mesenchymal morphology, partial loss of E-cadherin and gain of vimentin expression. Immunolocalization experiments showed a partial loss of E-cadherin at cell junctions and increased cytoplasmic localization of vimentin in leptin-treated cells. Moreover, chronic leptin treatment increased collective cell migration and invasion. Furthermore, when cultured in non-adherent conditions leptin treated cells exhibited reduced cell aggregation, increased survival, and decreased apoptosis, which correlates with increased FAK and AKT phosphorylation. Finally, bioinformatic analysis in two publicly available RNAseq datasets from normal breast tissue shows that high levels of leptin mRNA correlate positively with the expression of mesenchymal markers, and negatively with epithelial markers. Thus, our results demonstrate that chronic leptin treatment induces EMT in non-tumorigenic MCF10A cells and suggest that high leptin expression in normal breast tissue may induce EMT and contribute to increased risk of breast cancer.
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Neoplasias de la Mama , Transición Epitelial-Mesenquimal , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Cadherinas/metabolismo , Línea Celular , Línea Celular Tumoral , Células Epiteliales/metabolismo , Femenino , Humanos , Leptina/metabolismo , Leptina/farmacología , Vimentina/genética , Vimentina/metabolismo , Vimentina/farmacologíaRESUMEN
Orphan G-protein-coupled receptors (GPCR) comprise a large number of receptors which are widely distributed in the nervous system and represent an opportunity to identify new molecular targets in pain medicine. GPR55 and GPR119 are two orphan GPCR receptors whose physiological function is unclear. The aim was to explore the participation of spinal GPR55 and GPR119 in the processing of neuropathic pain in rats. Mechanical allodynia was evaluated using von Frey filaments. Protein localization and modulation were measured by immunohistochemistry and western blotting, respectively. Intrathecal administration of CID16020046 (selective GPR55 antagonist) or AS1269574 (selective GPR119 agonist) produced a dose-dependent antiallodynic effect, whereas O1062 (GPR55 agonist) and G-protein antagonist peptide dose-dependently prevented the antiallodynic effect of CID16020046 and AS1269574, respectively. Both GPR55 and GPR119 receptors were expressed in spinal cord, dorsal root ganglia and sciatic nerve, but only GPR119 was downregulated after 14 days of spinal nerve ligation. Data suggest that GPR55 and GPR119 participate in the processing of neuropathic pain and could be useful targets to manage neuropathic pain disorders.
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The efficacy of anti-obesity drugs usually does not consider the high degree of interindividual variability in responses to the drug which could affect the decision to withdraw the drug early due to ineffectiveness or to continue therapy according to specific expectations of success. The aim of this study was to analyze body weight loss in kilograms during the first month (1 mo-BWLkg) of treatment with 30 mg phentermine and development of tolerance to phentermine, on its 6-month efficacy. One hundred sixty-six subjects with obesity were individually or jointly analyzed in the study. Subjects with 1 mo-BWLkg of <1 kg, 1-3 kg, 3-5 kg, and ≥5 kg reached 6-month mean percentage body weight reductions (BWR%) of approximately 3%, 5%, 10%, and 15%, respectively. Development of late tolerance (4-6 months) to phentermine had a lower impact than early tolerance (2-3 months). Subjects with 1 mo-BWLkg < 3 kg who developed early tolerance did not achieve relevant BWR% (≥5%) at month 6, while the rest of the subgroups achieved increasing and progressive BWR%, according to their 1 mo-BWLkg range and time of onset of tolerance. The 1 mo-BWLkg and development of tolerance to phentermine could be useful to predict the expected 6-month efficacy trends in obese patients treated with 30 mg phentermine.
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BACKGROUND/AIM: Medication prescription is a fundamental component in the care of the elderly. Several characteristics of aging and geriatric medicine affect prescriptions for these people and make the selection of drug therapy a difficult and complex process. The objective of this study is to develop a geriatric portal for asynchronous online counseling (AGAlink) for use by physicians specializing in family medicine to reduce medication problems among older adult patients in the first level of care. METHOD: A qualitative study was carried out in the first level of care at the Mexican Institute of Social Security (IMSS), 31 family doctors were interviewed to identify attitudes, preferences about the use of the AGAlink geriatric portal, as well as their recommendations for the implementation of this tool in their daily practice. For the analysis of the data obtained, a qualitative thematic content analysis was used. RESULTS: 90% of the physicians used the geriatric portal outside office hours without the need for the patient to be present. The perception of the physician towards the use of the AGAlink geriatric portal was favorable, provided relevant information and had several positive effects on the process of care for medical prescription. The barriers identified to accept the change in medication were not having the proposed therapeutic option, lack of any laboratory analysis, continuing to consider their experience for the prescription of the medication. CONCLUSIONS: The AGAlink geriatric portal was a tool that was well received by physicians who expressed a positive attitude, considered an investment of a short time that allowed them to update and learn about strategies to reduce the prescription problems presented among the elderly population. However, the main barrier was the use of technology, especially in the doctors with more seniority in the service.
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Consejo , Geriatría , Prescripción Inadecuada , Internet , Atención Primaria de Salud , Adulto , Anciano , Femenino , Directrices para la Planificación en Salud , Humanos , Masculino , Encuestas y CuestionariosRESUMEN
This study aimed to explore the relationship between the inter-limb differences in unilateral countermovement (CMJ) height and the inter-limb differences in bilateral CMJ force production, and to elucidate whether the self-reported preferred leg contributes more to force production than the non-preferred leg. Twenty-three senior basketball players performed in a single session eight unilateral CMJs (four with each leg) and four bilateral CMJs. Impulse, peak force, mean force were recorded during the bilateral CMJ, and jump height during the unilateral CMJ. Small correlations were observed between the inter-limb differences in unilateral CMJ height and the inter-limb asymmetries in bilateral CMJ impulse, peak force, and mean force (p ≥ 0.171; r≤-0.142). The self-reported preferred leg revealed a higher performance in 7 out of 23 participants (Kappa = -0.20) for the unilateral CMJ height, 7 out of 23 participants (Kappa = -0.11) for the bilateral CMJ impulse, 6 out of 23 participants (Kappa = -0.36) for the bilateral CMJ peak force, and 8 out of 23 participants (Kappa = -0.34) for the bilateral CMJ mean force. These results highlight that the asymmetries detected during bilateral CMJs cannot be extrapolated to unilateral CMJs, and that the preferred leg generally contributes less to force production than the non-preferred leg during both bilateral and unilateral CMJs.