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1.
Ann Surg ; 279(1): 24-28, 2024 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-37641981

RESUMEN

OBJECTIVE: To evaluate the safety, efficacy, and cost-effectiveness of outpatient appendectomy in patients with uncomplicated acute appendicitis. BACKGROUND: Given that acute appendicitis is the most common cause of acute abdomen, the introduction of outpatient appendectomy protocols could significantly improve the effectiveness and sustainability of health care systems. METHODS: A total of 300 patients were enrolled from October 2018 to June 2021 in the PENDI-CSI randomized clinical trial: 149 were assigned to the outpatient surgery (OPS) group and 151 to the inpatient surgery (IPS) group, followed by 1 month postoperatively. All patients were aged older than 14 years and had uncomplicated acute appendicitis. Exclusion criteria were pregnancy, neoplasms, inflammatory bowel disease, and high anesthetic risk (ASA IV). The OPS group was discharged from the postanesthesia care unit while the IPS group was admitted. RESULTS: In total, 128 patients in the OPS group (85.9%) were discharged without admission. Predictors whether patients in the OPS group had to be admitted were aged over 31 years [relative risk (RR): 2.42 (1.04-5.65)], hypertension [RR: 6.21 (3.22-11.97)], anesthetic risk II-III [RR: 2.63 (1.17-5.94)], previous abdominal surgery [RR: 3.34 (1.55-7.20)], postoperative pain with visual analog scale >6 [RR: 4.28 (2.67-6.86)], and postoperative fear [RR: 2.2 (1.04-4.67)]. There were no differences in terms of complications, readmissions, and reinterventions, and the perceived quality was similar in both groups. The outpatient modality produced savings of €1 034.97 per patient ( P < 0.001). CONCLUSIONS: Outpatient appendectomy is safe and effective for uncomplicated acute appendicitis. Patient-perceived quality is similar to that of IPS, although it successfully reduces hospital costs compared with inpatient appendectomy.


Asunto(s)
Anestésicos , Apendicitis , Humanos , Anciano , Apendicitis/cirugía , Apendicitis/tratamiento farmacológico , Análisis Costo-Beneficio , Procedimientos Quirúrgicos Ambulatorios , Apendicectomía/métodos , Enfermedad Aguda , Resultado del Tratamiento , Antibacterianos/uso terapéutico
2.
J Am Acad Dermatol ; 90(1): 125-132, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37454698

RESUMEN

Pressure-induced alopecias (PAs) are an infrequent group of scarring and nonscarring alopecias that occur after ischemic obstruction of capillaries that leads to circumscribed areas of hair loss. Initially described after prolonged surgeries or immobilization, type 1 PA occurs after sustained external pressure to the skin, mainly the scalp prominences. Alopecia induced by cosmetic procedures, referred in this review as type 2 PA, is reported with increased frequency in literature and predominantly emerges from pressure exerted by the volume of injectables. It is important to differentiate type 2 PA from vascular occlusion-induced alopecia because they represent distinct entities. Clinically, PA may present with erythema, swelling, and tenderness; however, alopecia might be the sole manifestation. Crusts and ulceration are associated with a worse outcome and a higher risk of scarring alopecia. Prompt diagnosis is paramount to prevent complications. Trichoscopy, although considered nonspecific, may provide relevant clues for an accurate diagnosis. Hair regrows in most cases, but prognosis depends on ischemia severity and timely treatment with reperfusion therapies or mobilization. Treatment of hair loss is usually not necessary because the disease in most cases is self-limited and reversible. The role of topical minoxidil and corticosteroids remains unknown.


Asunto(s)
Alopecia , Cicatriz , Humanos , Cicatriz/terapia , Cicatriz/complicaciones , Alopecia/diagnóstico , Alopecia/etiología , Alopecia/terapia , Cabello/patología , Cuero Cabelludo/patología , Piel
3.
Neurosurg Focus ; 54(1): E3, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36587405

RESUMEN

OBJECTIVE: The aim of this paper was to evaluate the changes in radiographic spinopelvic parameters in a large cohort of patients undergoing the prone transpsoas approach to the lumbar spine. METHODS: A multicenter retrospective observational cohort study was performed for all patients who underwent lateral lumber interbody fusion via the single-position prone transpsoas (PTP) approach. Spinopelvic parameters from preoperative and first upright postoperative radiographs were collected, including lumbar lordosis (LL), pelvic incidence (PI), and pelvic tilt (PT). Functional indices (visual analog scale score), and patient-reported outcomes (Oswestry Disability Index) were also recorded from pre- and postoperative appointments. RESULTS: Of the 363 patients who successfully underwent the procedure, LL after fusion was 50.0° compared with 45.6° preoperatively (p < 0.001). The pelvic incidence-lumbar lordosis mismatch (PI-LL) was 10.5° preoperatively versus 2.9° postoperatively (p < 0.001). PT did not significantly change (0.2° ± 10.7°, p > 0.05). CONCLUSIONS: The PTP approach allows significant gain in lordotic augmentation, which was associated with good functional results at follow-up.


Asunto(s)
Lordosis , Fusión Vertebral , Humanos , Estudios Retrospectivos , Lordosis/diagnóstico por imagen , Lordosis/cirugía , Complicaciones Posoperatorias/epidemiología , Fusión Vertebral/métodos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Resultado del Tratamiento
4.
Salud Publica Mex ; 65: s15-s22, 2023 Jun 08.
Artículo en Español | MEDLINE | ID: mdl-38060950

RESUMEN

OBJETIVO: Presentar un panorama descriptivo de las elecciones de la población mexicana frente a una necesidad de salud en 2022. Material y métodos. Se utilizaron datos de la Encuesta Nacional de Salud y Nutrición Continua 2022. RESULTADOS: De 24.6% de la población que informó haber tenido una necesidad de salud en los últimos tres meses, 44% recibió atención en servicios públicos. El uso de servicios privados es extensivo a toda la población, pero fue más elevado en aquellos sin derechohabiencia. Se encontró que 71% de los motivos por los que las personas no se atendieran en el lugar que les correspondía de acuerdo con su derechohabiencia tuvo que ver con el acceso y 21% con la percepción de calidad. Entre los motivos de acceso para elegir el lugar donde se atendieron destacan la afiliación, la cercanía y el costo. En cuanto a la calidad, resaltan la atención rápida y la satisfacción con la atención. CONCLUSIONES: Con el fin de reducir la desigualdad de acceso y el gasto de bolsillo asociado con un mayor uso de servicios privados, sobre todo entre la población sin seguridad social, mejorar el acceso (como la distancia, los horarios de atención, las barreras burocráticas) puede ayudar a avanzar en este objetivo.

5.
Neuromodulation ; 26(2): 292-301, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35840520

RESUMEN

OBJECTIVES: The aim of this study was to examine the current scientific literature on deep brain stimulation (DBS) targeting the habenula for the treatment of neuropsychiatric disorders including schizophrenia, major depressive disorder, and obsessive-compulsive disorder (OCD). MATERIALS AND METHODS: Two authors performed independent data base searches using the PubMed, Cochrane, PsycINFO, and Web of Science search engines. The data bases were searched for the query ("deep brain stimulation" and "habenula"). The inclusion criteria involved screening for human clinical trials written in English and published from 2007 to 2020. From the eligible studies, data were collected on the mean age, sex, number of patients included, and disorder treated. Patient outcomes of each study were summarized. RESULTS: The search yielded six studies, which included 11 patients in the final analysis. Treated conditions included refractory depression, bipolar disorder, OCD, schizophrenia, and major depressive disorder. Patients with bipolar disorder unmedicated for at least two months had smaller habenula volumes than healthy controls. High-frequency stimulation of the lateral habenula attenuated the rise of serotonin in the dorsal raphe nucleus for treating depression. Bilateral habenula DBS and patient OCD symptoms were reduced and maintained at one-year follow up. Low- and high-frequency stimulation DBS can simulate input paths to the lateral habenula to treat addiction, including cocaine addiction. More data are needed to draw conclusions as to the impact of DBS for schizophrenia and obesity. CONCLUSIONS: The habenula is a novel target that could aid in reducing neuropsychiatric symptoms and should be considered in circuit-specific investigation of neuromodulation for psychiatric disorders. More information needs to be gathered and assessed before this treatment is fully approved for treatment of neuropsychiatric conditions.


Asunto(s)
Trastorno Depresivo Mayor , Trastorno Obsesivo Compulsivo , Humanos , Trastorno Depresivo Mayor/terapia , Trastorno Depresivo Mayor/psicología , Trastorno Obsesivo Compulsivo/terapia , Encéfalo
6.
Int J Mol Sci ; 24(5)2023 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-36902005

RESUMEN

T lymphocytes are key players in adaptive immune responses through the recognition of peptide antigens through the T Cell Receptor (TCR). After TCR engagement, a signaling cascade is activated, leading to T cell activation, proliferation, and differentiation into effector cells. Delicate control of activation signals coupled to the TCR is needed to avoid uncontrolled immune responses involving T cells. It has been previously shown that mice deficient in the expression of the adaptor NTAL (Non-T cell activation linker), a molecule structurally and evolutionarily related to the transmembrane adaptor LAT (Linker for the Activation of T cells), develop an autoimmune syndrome characterized by the presence of autoantibodies and enlarged spleens. In the present work we intended to deepen investigation into the negative regulatory functions of the NTAL adaptor in T cells and its potential relationship with autoimmune disorders. For this purpose, in this work we used Jurkat cells as a T cell model, and we lentivirally transfected them to express the NTAL adaptor in order to analyze the effect on intracellular signals associated with the TCR. In addition, we analyzed the expression of NTAL in primary CD4+ T cells from healthy donors and Rheumatoid Arthritis (RA) patients. Our results showed that NTAL expression in Jurkat cells decreased calcium fluxes and PLC-γ1 activation upon stimulation through the TCR complex. Moreover, we showed that NTAL was also expressed in activated human CD4+ T cells, and that the increase of its expression was reduced in CD4+ T cells from RA patients. Our results, together with previous reports, suggest a relevant role for the NTAL adaptor as a negative regulator of early intracellular TCR signaling, with a potential implication in RA.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Artritis Reumatoide , Humanos , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Células Jurkat , Proteínas de la Membrana/metabolismo , Fosfoproteínas/metabolismo , Fosforilación , Receptores de Antígenos de Linfocitos T/metabolismo
7.
Int J Mol Sci ; 24(13)2023 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-37445668

RESUMEN

Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV- reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs.


Asunto(s)
Antígeno de Maduración de Linfocitos B , Citomegalovirus , Humanos , Antígeno de Maduración de Linfocitos B/genética , Antígeno de Maduración de Linfocitos B/metabolismo , Estudios Prospectivos , Viremia , Proteína Activadora Transmembrana y Interactiva del CAML/genética , Factor Activador de Células B/genética , Inmunoglobulina G
8.
Molecules ; 28(21)2023 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-37959657

RESUMEN

pH regulation is essential to allow normal cell function, and their imbalance is associated with different pathologic situations, including cancer. In this study, we present the synthesis of 2-(((2-aminoethyl)imino)methyl)phenol (HL1) and the iron (III) complex (Fe(L1)2Br, (C1)), confirmed by X-ray diffraction analysis. The absorption and emission properties of complex C1 were assessed in the presence and absence of different physiologically relevant analytes, finding a fluorescent turn-on when OH- was added. So, we determined the limit of detection (LOD = 3.97 × 10-9 M), stoichiometry (1:1), and association constant (Kas = 5.86 × 103 M-1). Using DFT calculations, we proposed a spontaneous decomposition mechanism for C1. After characterization, complex C1 was evaluated as an intracellular pH chemosensor on the human primary gastric adenocarcinoma (AGS) and non-tumoral gastric epithelia (GES-1) cell lines, finding fluorescent signal activation in the latter when compared to AGS cells due to the lower intracellular pH of AGS cells caused by the increased metabolic rate. However, when complex C1 was used on metastatic cancer cell lines (MKN-45 and MKN-74), a fluorescent turn-on was observed in both cell lines because the intracellular lactate amount increased. Our results could provide insights about the application of complex C1 as a metabolic probe to be used in cancer cell imaging.


Asunto(s)
Colorantes Fluorescentes , Hierro , Humanos , Hierro/análisis , Colorantes Fluorescentes/química , Línea Celular , Concentración de Iones de Hidrógeno , Espectrometría de Fluorescencia/métodos
9.
Molecules ; 28(2)2023 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-36677645

RESUMEN

Women have a high susceptibility to the negative effects of stress. Hormonal changes experienced throughout their reproductive life partially contribute to a higher incidence of anxiety and depression symptoms, particularly, during natural or surgical menopause. In preclinical research, the flavonoid chrysin (5,7-dihydroxyflavone) exerts anxiolytic- and anti-despair-like effects; however, it is unknown whether chrysin exerts a protective effect against the behavioral changes produced by acute stress on locomotor activity and behavioral despair in rats at 12-weeks post-ovariectomy. Ovariectomized female Wistar rats were assigned to eight groups: vehicle group (10% DMSO), three groups with chrysin and three groups with the same dose of allopregnanolone (0.5, 1, and 2 mg/kg), and one group with diazepam (2 mg/kg). The treatments were administered for seven consecutive days and the effects were evaluated in the locomotor activity and swimming tests. Chrysin (2 mg/kg) increased the latency to first immobility and decreased the total immobility time in the swimming test as the reference drugs allopregnanolone and diazepam (2 mg/kg); while locomotor activity prevented the behavioral changes produced by swimming. In conclusion, chrysin exerts a protective effect against the behavioral changes induced by acute stress, similarly to the neurosteroid allopregnanolone and the benzodiazepine diazepam in rats subjected to a surgical menopause model.


Asunto(s)
Flavonoides , Pregnanolona , Ratas , Femenino , Animales , Ratas Wistar , Pregnanolona/farmacología , Flavonoides/farmacología , Diazepam/farmacología , Menopausia
10.
BMC Infect Dis ; 22(1): 96, 2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35090394

RESUMEN

BACKGROUND: At the end of 2019, a novel coronavirus denominated SARS-CoV-2 rapidly spread through the world causing the pandemic coronavirus disease known as COVID-19. The difference in the inflammatory response against SARS-CoV-2 infection among people living at different altitudes is a variable not yet studied. METHODS: A descriptive cross-sectional study was performed in two Peruvian cities at different altitudes for comparison: Lima and Huaraz. Five important proinflammatory cytokines were measured including: IL-6, IL-2, IL-10, IFN-γ and TNF-α using ELISA assays. RESULTS: A total of 35 COVID-19 patients and 10 healthy subjects were recruited from each study site. The mean levels of IL-6 (p < 0.03) and TNF-α (p < 0.01) were significantly different among the study groups. In the case of IL-6, patients from Lima had a mean level of 16.2 pg/ml (healthy) and 48.3 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 67.3 pg/ml (healthy) and 97.9 pg/ml (COVID-19). Regarding TNF-α, patients from Lima had a mean level of 25.9 pg/ml (healthy) and 61.6 pg/ml (COVID-19), meanwhile, patients from Huaraz had levels of 89.0 pg/ml (healthy) and 120.6 pg/ml (COVID-19). The levels of IL-2, IL-10 and IFN-γ were not significantly different in the study groups. CONCLUSION: Patients with COVID-19 residing at high-altitude tend to have higher levels of inflammatory cytokines compared to patients living at sea level, particularly IL-6 and TNF-α. A better understanding of the inflammatory response in different populations can contribute to the implementation of therapeutic and preventive approaches. Further studies evaluating more patients, a greater variety of cytokines and their clinical impact are required.


Asunto(s)
Altitud , COVID-19 , Estudios Transversales , Citocinas , Humanos , SARS-CoV-2
11.
J Fluoresc ; 32(4): 1449-1456, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35441925

RESUMEN

Mercury (Hg) is an element with high toxicity, especially to the nervous system, and fluorescent pigments are used to visualize dynamic processes in living cells. A little explored fluorescent core is chalcone. Herein, we synthesized chalcone (2E)-3-(4-(dimethylamino)phenyl)-1-phenylprop-2-en-1-one (8) and assessed its photophysical properties. Moreover, the application of this chemosensor in aqueous media shows a selective fluorescence quenching effect with Hg(II). The figures of merit for the chemosensor were calculated to be LOD = 136 nM and LOQ = 454 nM, as well as a stoichiometry of 1:1. Furthermore, the association constant (Ka) and fluorescence quenching constant (KSV) were calculated using the Benesi-Hildebrand and Stern-Volmer equations to be Ka= 9.08 × 104 and KSV= 1.60 × 105, respectively. Finally, by using a computational approach, we explain the interaction between chalcone (8) and Hg(II) and propose a potential quenching mechanism based on the blocking of photoinduced electron transfer.


Asunto(s)
Chalconas , Mercurio , Colorantes Fluorescentes , Espectrometría de Fluorescencia , Agua
12.
Eur Spine J ; 31(1): 95-103, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34599407

RESUMEN

PURPOSE: Multiple-rod constructs (MRCs) are often used in deformity correction for increased stability and rigidity. There are currently no reports showing minimally invasive placement of MRCs in adult deformity surgery and its technical feasibility through preoperative software planning. METHODS: Data were collected retrospectively from medical records of six consecutive patients who underwent minimally invasive MRCs with robotics planning by a single surgeon at an academic center between March-August 2020. RESULTS: A total of six patients (4 females, mean age 69.7 years) underwent minimally invasive long-segment (6 +) posterior fixation with multiple rods (3 +) using the Mazor X Stealth Edition robotics platform. Average follow-up was 14.3 months. All patients underwent oblique lumbar interbody fusion (OLIF) as a first stage, followed by second stage posterior fixation in the same day. The mean number of levels posteriorly instrumented was 8.8. One patient underwent 3 rod fixation (1 iliac, 2 S2AI) and 5 patients underwent quad rod fixation (2 iliac, 2 S2AI). The mean time to secure all rods was 8 min 36 s. Mean improvement in spinopelvic parameters was -4.9 cm sagittal vertical axis, 18.0° lumbar lordosis, and -10.7° pelvic tilt with an average pelvic incidence of 62.5°. Estimated blood loss (EBL) was 100-250 cc with no blood transfusions, and all but one patient ambulated on postoperative day 1 or 2. CONCLUSION: Spinal robotics brings us into a new era of minimally invasive construct design. To our knowledge, this is the first description of the technical feasibility of MRCs in minimally invasive adult spinal deformity surgery.


Asunto(s)
Lordosis , Fusión Vertebral , Adulto , Anciano , Femenino , Humanos , Lordosis/cirugía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Retrospectivos , Resultado del Tratamiento
13.
Arch Pharm (Weinheim) ; 355(7): e2200042, 2022 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-35435270

RESUMEN

Neuroblastoma is one of the most frequent types of cancer found in infants, and traditional chemotherapy has limited efficacy against this pathology. Thus, the development of new compounds with higher activity and selectivity than traditional drugs is a current challenge in medicinal chemistry research. In this study, we report the synthesis of 21 chalcones with antiproliferative activity and selectivity against the neuroblastoma cell line SH-SY5Y. Then, we developed three-dimensional quantitative structure-activity relationship models (comparative molecular field analysis and comparative molecular similarity index analysis) with high-quality statistical values (q2 > 0.7; r2 > 0.8; r2 pred > 0.7), using IC50 and selectivity index (SI) data as dependent variables. With the information derived from these theoretical models, we designed and synthesized 16 new molecules to prove their consistency, finding good antiproliferative activity against SH-SY5Y cells on these derivatives, with three of them showing higher SI than the referential drugs 5-fluorouracil and cisplatin, displaying also a proapoptotic effect comparable to these drugs, as proven by measuring their effects on executor caspases 3/7 activity induction, Bcl-2/Bax messenger RNA levels alteration, and DNA fragmentation promotion.


Asunto(s)
Antineoplásicos , Chalcona , Chalconas , Neuroblastoma , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Chalcona/farmacología , Chalconas/farmacología , Humanos , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/patología , Relación Estructura-Actividad Cuantitativa
14.
Molecules ; 27(3)2022 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-35164192

RESUMEN

Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (endo coumarin-resveratrol-inspired hybrid) and trans-6-styrylcoumarin (exo coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with trans-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than trans-resveratrol.


Asunto(s)
Cumarinas/química , Inhibidores de la Monoaminooxidasa/farmacología , Monoaminooxidasa/efectos de los fármacos , Resveratrol/química , Estirenos/química , Dominio Catalítico , Simulación del Acoplamiento Molecular
15.
Bioorg Chem ; 108: 104689, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33571810

RESUMEN

Monoamine oxidases (MAOs) are important targets in medicinal chemistry, as their inhibition may change the levels of different neurotransmitters in the brain, and also the production of oxidative stress species. New chemical entities able to interact selectively with one of the MAO isoforms are being extensively studied, and chalcones proved to be promising molecules. In the current work, we focused our attention on the understanding of theoretical models that may predict the MAO-B activity and selectivity of new chalcones. 3D-QSAR models, in particular CoMFA and CoMSIA, and docking simulations analysis have been carried out, and their successful implementation was corroborated by studying twenty-three synthetized chalcones (151-173) based on the generated information. All the synthetized molecules proved to inhibit MAO-B, being ten out of them MAO-B potent and selective inhibitors, with IC50 against this isoform in the nanomolar range, being (E)-3-(4-hydroxyphenyl)-1-(2,2-dimethylchroman-6-yl)prop-2-en-1-one (152) the best MAO-B inhibitor (IC50 of 170 nM). Docking simulations on both MAO-A and MAO-B binding pockets, using compound 152, were carried out. Calculated affinity energy for the MAO-A was +2.3 Kcal/mol, and for the MAO-B was -10.3 Kcal/mol, justifying the MAO-B high selectivity of these compounds. Both theoretical and experimental structure-activity relationship studies were performed, and substitution patterns were established to increase MAO-B selectivity and inhibitory efficacy. Therefore, we proved that both 3D-QSAR models and molecular docking approaches enhance the probability of finding new potent and selective MAO-B inhibitors, avoiding time-consuming and costly synthesis and biological evaluations.


Asunto(s)
Chalconas/síntesis química , Inhibidores de la Monoaminooxidasa/síntesis química , Monoaminooxidasa/metabolismo , Secuencia de Aminoácidos , Dominio Catalítico , Chalconas/metabolismo , Diseño de Fármacos , Enlace de Hidrógeno , Interacciones Hidrofóbicas e Hidrofílicas , Concentración 50 Inhibidora , Simulación del Acoplamiento Molecular , Inhibidores de la Monoaminooxidasa/metabolismo , Unión Proteica , Conformación Proteica , Relación Estructura-Actividad Cuantitativa , Termodinámica
16.
Langenbecks Arch Surg ; 406(5): 1581-1589, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33409584

RESUMEN

INTRODUCTION: There is still controversy regarding the ideal technique to close the appendicular stump in laparoscopic appendectomy (LA). The objective of this study was to determine the safety and efficiency of the use of an endoloop (EL) and endostapler (ES) in complicated and uncomplicated acute appendicitis. METHODS: Retrospective cohort study of patients undergoing LA from February 2013 to December 2019. Acute uncomplicated and complicated appendicitis were analysed separately, establishing two groups according to the stump closure technique: EL or ES. Seven hundred-nine patients were included (535 uncomplicated and 174 complicated). In uncomplicated appendicitis, an EL was used in 447 of the patients (83.55%) and an ES was used in 88 patients (16.45%). In complicated appendicitis, an EL was used in 85 patients (48.85%) and an ES was used in 89 patients (51.15%). An analysis of effectiveness and a cost analysis of each technique were performed. RESULTS: In uncomplicated appendicitis, we found no differences with respect to global complications, although there were significant differences in the total mean hospital stay (EL group 1.55 (SD 1.48) days; ES group 2.21 (SD 1.69) days; p = 0.046). This meant a savings of 514.12€ per patient using the EL p < 0.001). In complicated appendicitis, the reoperations classified as Clavien-Dindo IIIB in the EL group (6.4%) were greater than in the ES group (0%) (p = 0.012), although the rate of postoperative abscesses (p = 0.788) and the mean volume of abscesses (p = 0.891) were similar. CONCLUSION: The systematic use of an EL could reduce costs in uncomplicated appendicitis, while in complicated cases, both options are valid. Prospective studies with a greater number of patients are needed to observe differences in postoperative complications.


Asunto(s)
Apendicitis , Laparoscopía , Apendicectomía/efectos adversos , Apendicitis/cirugía , Humanos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Estudios Prospectivos , Estudios Retrospectivos
17.
Salud Publica Mex ; 63(6, Nov-Dic): 734-742, 2021 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-35099913

RESUMEN

OBJECTIVE: The study describes health care services utilization contextualized by the needs of the Mexican population during the Covid-19 pandemic. MATERIALS AND METHODS: We used data from the National Health and Nutrition Survey, Covid-19. Among the population with symptoms compatible with Covid-19, we describe the proportion who sought care, received care, were tested, were diagnosed positive, and survived, and whether they received care in public or private services. We estimated factors associated with the probability of seeking and receiving care. RESULTS: Out of 7.1% of the population with symptoms compatible with Covid-19, 64.4% received care, and 15.4% tested positive; 74.5% received care in the private sector, even among the population with social security. Those with social security, in contact with a suspected or confirmed Covid-19 case, and with at least one comorbidity had a higher probability of seeking and receiving care. CONCLUSIONS: The most relevant finding of our study is the large proportion of the population with Covid-19 symptoms who sought and received care in private facilities an essential aspect for decision-makers to consider as the current health reform moves forward in Mexico.


Asunto(s)
COVID-19 , Pandemias , Reforma de la Atención de Salud , Humanos , México/epidemiología , SARS-CoV-2
18.
Salud Publica Mex ; 63(4): 575-582, 2021 06 18.
Artículo en Español | MEDLINE | ID: mdl-34098599

RESUMEN

Objective: Estimate the price and income elasticities of the demand for beer in Mexico. Materials and methods: Monthly series on beer sales and prices from 2007 to 2019 were used. Long-term elasticity was estimated using ordinary least squares (OLS). Short-term elasticity was estimated using a dynamic ordinary least squares (DOLS) model. Results: The price elasticity was in the long term of -1.40 (95%CI: -2.53 to -0.27) and -1.31 (95%CI: -2.46 to -0.15) in the short term. The income elasticity of demand in the long and short term was estimated at 0.86 (95%CI: 0.44-1.29 and 0.93 (95%CI: 0.51-1.34), respectively. Conclusions: The findings of this study suggest that fiscal policies may have a positive impact on the health of the population by reducing beer consumption.


Asunto(s)
Cerveza , Impuestos , Comercio , Elasticidad , Humanos , Renta , México
19.
J Therm Biol ; 99: 102980, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34420624

RESUMEN

Thermoregulation is a critical process for ectotherms as non-avian reptiles, since their vital physiological processes depend on it. These organisms have a temperature range where their physiological processes are more efficient, this range is usually a requirement set phylogenetically even though they vary in the use of habitats. This research compares the thermal ecophysiology of Basiliscus galeritus (western basilisk) in two populations with altitudinal differences in the northwestern of Ecuador. The results suggest that the difference of altitude between the two locations (500 m) influences the thermal ecophysiology of the species since the body temperature (Tb), operative temperature (Te) and preferred body temperature (Tset) showed significative differences. Furthermore, B. galeritus obtains its Tb through heliothermy and it behaves as an active thermoregulator. On the other hand, the crest temperatures reach higher values than their Tset, the results suggested that the species uses the crest as an alternative to regulate its body temperature when exceeding its Tset. Besides, this thermoregulatory behavior has been suggested only in some extinct synapsids.


Asunto(s)
Regulación de la Temperatura Corporal , Lagartos/fisiología , Altitud , Animales , Ecosistema , Femenino , Masculino
20.
Neurobiol Dis ; 141: 104938, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32434047

RESUMEN

INTRODUCTION: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in elderly people. Existent therapies are directed at alleviating some symptoms, but are not effective in altering the course of the disease. METHODS: Based on our previous study that showed that an Aß-interacting small peptide protected against the toxic effects of amyloid-beta peptide (Aß), we carried out an array of in silico, in vitro, and in vivo assays to identify a molecule having neuroprotective properties. RESULTS: In silico studies showed that the molecule, referred to as M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine), was able to interact with the Aß peptide. Additionally, in vitro assays showed that M30 blocked Aß aggregation, association to the plasma membrane, synaptotoxicity, intracellular calcium, and cellular toxicity, while in vivo experiments demonstrated that M30 induced a neuroprotective effect by decreasing the toxicity of Aß in the dentate gyrus of the hippocampus and improving the alteration in spatial memory in behavior assays. DISCUSSION: Therefore, we propose that this new small molecule could be a useful candidate for the additional development of a treatment against AD since it appears to block multiple steps in the amyloid cascade. Overall, since there are no drugs that effectively block the progression of AD, this approach represents an innovative strategy. SIGNIFICANCE: Currently, there is no effective treatment for AD and the expectations to develop an effective therapy are low. Using in silico, in vitro, and in vivo experiments, we identified a new compound that is able to inhibit Aß-induced neurotoxicity, specifically aggregation, association to neurons, synaptic toxicity, calcium dyshomeostasis and memory impairment induced by Aß. Because Aß toxicity is central to AD progression, the inhibition mediated by this new molecule might be useful as a therapeutic tool.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Agregación Patológica de Proteínas/prevención & control , Animales , Simulación por Computador , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Simulación del Acoplamiento Molecular , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Células PC12 , Agregación Patológica de Proteínas/metabolismo , Ratas
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