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1.
bioRxiv ; 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38979190

ABSTRACT

The overexpression of proto-oncogenic protein Bcl3 is observed in various cancers. Bcl3 is extensively phosphorylated and associates with NF-κB p50 and p52 homodimers to regulate transcription. Through cellular and biochemical assays, we observed that phospho-mimetic Glu substitution of Bcl3 Ser366 in addition to previously studied Ser33, 114 and 446 is necessary to switch it from an IκB-like inhibitor to a transcriptional activator. To study interactive features of p52 homodimer and Bcl3, and phospho-modification mediated changes in Bcl3 that regulates DNA-binding by p52, we performed HDX-MS of both Bcl3 and p52 within various complexes. Nature of interactions within Bcl3:(p52:p52) complex in presence and absence of DNA, and differential flexibility and allosteric changes in Bcl3 upon phospho-modifications revealed why a facile accommodation of DNA requires phosphorylations. The inhibitory nature of unphosphorylated Bcl3:(p52:p52) complex for DNA binding was also relieved by deletion of Bcl3 C-terminal 28 residues. Overall, this study revealed mechanistic bases of how phospho-modification of Bcl3 regulate transcriptional potential of NF-κB and intricate cell physiology, a dysregulation of which can lead to cancers.

2.
bioRxiv ; 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38370807

ABSTRACT

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed a novel approach-avoidance conflict model using a modified conditioned place preference paradigm to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision making. Upon establishment of morphine conditioned place preference, rats underwent a subsequent conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline control group avoided the cat odor side, the morphine group maintained preference for the paired side despite the presence of cat odor. K-means clustering identified two subsets of morphine-treated rats that exhibited either persistent drug seeking (Risk-Takers) or increased avoidance (Risk-Avoiders) during conflict. Single-unit recordings from the prelimbic cortex (PL) revealed decreased neuronal firing rates upon acute morphine exposure in both Risk-Takers and Risk-Avoiders, but this firing rate suppression was absent after repeated administration. Risk-Avoiders also displayed distinct post-morphine excitation in PL which persisted across conditioning. During the preference test, subpopulations of PL neurons in all groups were either excited or inhibited when rats entered the paired side. Interestingly, while this inhibitory signal was lost during the subsequent conflict test in both saline and Risk-Avoider groups, these inhibitory responses persisted in Risk-Takers. Our results suggest that loss of PL inhibition after opioid conditioning is associated with the formation of contextual reward memory. Furthermore, persistent PL inhibitory signaling in the drug-associated context during conflict may underlie increased risk taking following opioid exposure.

3.
Eur Phys J C Part Fields ; 83(10): 939, 2023.
Article in English | MEDLINE | ID: mdl-37869055

ABSTRACT

The calculation of P-wave Sommerfeld enhancement in processes with unstable particles in the final state is known to be divergent. In a complete description, where resonant (on-shell unstable particles) and non-resonant contributions are included, it has been shown that results are finite. For most beyond the Standard Model applications, these complete calculations are not readily available. In this work, we are interested in the near-threshold region and we consider only the resonant contribution. In this case, we provide a simplified prescription to compute the P-wave Sommerfeld enhancement in the narrow-width approximation of the unstable particle that directly eliminates divergences. We show that we can define a finite resonant contribution without the inclusion of the non-resonant processes in a way similar to the usual S-wave Sommerfeld enhancement.

4.
Int. j. morphol ; 41(5): 1310-1316, oct. 2023. tab
Article in English | LILACS | ID: biblio-1521015

ABSTRACT

SUMMARY: Although COVID-19 is primarily considered a respiratory pathology, it has been observed to impact other bodily systems, including the nervous system. While several studies have investigated anatomical changes in brain structures, such as volume or thickness post-COVID-19, there are no comprehensive reviews of these changes using imaging techniques for a holistic understanding. The aim of this study was to systematically analyze the literature on brain changes observed through neuroimaging after COVID-19. We conducted a systematic review according to PRISMA guidelines using Web of Science, Scopus, Medline, Pubmed, Sciencedirect, and LitCOVID. We selected studies that included adult patients during or after COVID-19 development, a control group or pre-infection images, and morphometric measurements using neuroimaging. We used the MSQ scale to extract information on sample characteristics, measured anatomical structures, imaging technique, main results, and methodological quality for each study. Out of 1126 identified articles, we included 19 in the review, encompassing 1155 cases and 1284 controls. The results of these studies indicated a lower volume of the olfactory bulb and variable increases or decreases in cortical and limbic structures' volumes and thicknesses. Studies suggest that brain changes occur post-COVID-19, primarily characterized by a smaller olfactory bulb. Additionally, there may be variations in cortical and limbic volumes and thicknesses due to inflammation or neuroplasticity, but these findings are not definitive. These differences may be attributed to methodological, geographical, and temporal variations between studies. Thus, additional studies are required to provide a more comprehensive and quantitative view of the evidence.


Aunque el COVID-19 se considera principalmente una patología respiratoria, se ha observado que afecta otros sistemas corporales, incluido el sistema nervioso. Si bien varios estudios han investigado los cambios anatómicos en las estructuras cerebrales, como el volumen o el grosor posteriores a la COVID-19, no hay revisiones exhaustivas de estos cambios que utilicen técnicas de imágenes para una comprensión holística. El objetivo de este estudio fue analizar sistemáticamente la literature sobre los cambios cerebrales observados a través de neuroimagen después de COVID-19. Realizamos una revisión sistemática de acuerdo con las pautas PRISMA utilizando Web of Science, Scopus, Medline, Pubmed, Sciencedirect y LitCOVID. Seleccionamos estudios que incluyeron pacientes adultos durante o después del desarrollo de COVID-19, un grupo de control o imágenes previas a la infección y mediciones morfométricas mediante neuroimagen. Utilizamos la escala MSQ para extraer información sobre las características de la muestra, las estructuras anatómicas medidas, la técnica de imagen, los principales resultados y la calidad metodológica de cada estudio. De 1126 artículos identificados, incluimos 19 en la revisión, que abarca 1155 casos y 1284 controles. Los resultados de estos estudios indicaron un menor volumen del bulbo olfatorio y aumentos o disminuciones variables en los volúmenes y espesores de las estructuras corticales y límbicas. Los estudios sugieren que los cambios cerebrales ocurren después del COVID-19, caracterizados principalmente por un bulbo olfatorio más pequeño. Además, pueden haber variaciones en los volúmenes y grosores corticales y límbicos debido a la inflamación o la neuroplasticidad, pero estos hallazgos no son definitivos. Estas diferencias pueden atribuirse a variaciones metodológicas, geográficas y temporales entre estudios. Por lo tanto, se requieren estudios adicionales para proporcionar una visión más completa y cuantitativa de la evidencia.


Subject(s)
Humans , Brain/pathology , Brain/diagnostic imaging , COVID-19/complications , Neuroimaging , Neurologic Manifestations
5.
Br J Radiol ; 96(1148): 20221096, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37194990

ABSTRACT

Nephrocalcinosis refers to calcium deposition in the form of calcium oxalate or calcium phosphate in the renal parenchyma and tubules. After diagnosis, the cause of nephrocalcinosis must be established to carry out a comprehensive approach to this entity. Although this is a common finding, it can be underdiagnosed due to the lack of knowledge of the different presentation patterns that exist. Many causes have been described related to this disease.A pictorial review about the most common features of cortical and medullary nephrocalcinosis both in ultrasound and CT is presented in the present work as well as a review of its main causes and graphics to easily recognize each pattern.


Subject(s)
Nephrocalcinosis , Humans , Nephrocalcinosis/diagnostic imaging , Nephrocalcinosis/etiology , Kidney/diagnostic imaging , Calcium Oxalate , Radiography
6.
Interv Neuroradiol ; : 15910199231153195, 2023 Feb 07.
Article in English | MEDLINE | ID: mdl-36751025

ABSTRACT

BACKGROUND AND AIMS: Endovascular treatment for cerebrovascular disease is accepted as a first-line option with level I evidence in patients with an early and late time of window of onset symptoms, and an additional option in patients who do not respond or with contraindications to systemic thrombolysis; nevertheless the efficacy and outcomes of some groups were not clear, one of them are patients aged 80 years and older, because they were excluded of the trials, so the evidence is controversial with significant heterogeneity, for that reason in our study, we decided to analyze the age in the patients treated in our stroke center, as a predictor of prognosis, and to provide a baseline for the establishment of personalized treatment plans. METHODS: Observational, retrospective study of patients that received endovascular treatment for cerebrovascular disease in a Colombian stroke center between 2016 and 2020, continuous and categorical variables were compared using the Student's t test and Chi-Square. To determine cut-off points in the variable against death and Rankin score variable on 90th day. RESULTS: In total, 108 patients were recruited, 35 of them were of 80 or more years, and the mean age was 72.7 years, we found age as a significant variable to predict the risk in the population over 80 years of age [RR 3.37 CI (95% 1.14-103) p = 0.029]. CONCLUSIONS: Age younger than 80 is a significant predictor for results and long-term outcomes in patients suffering from stroke, and in patients older than 80 years old a Thrombolysis in Cerebral Infarction score 2b-3 is a predictor of good outcomes. Further studies are needed to evaluate the relationship between intrahospital complications and long-term outcomes.

7.
J Pediatr Gastroenterol Nutr ; 76(5): 640-645, 2023 05 01.
Article in English | MEDLINE | ID: mdl-36763993

ABSTRACT

OBJECTIVES: Pediatric autoimmune pancreatitis (P-AIP) is an uncommon disease whose diagnosis requires strong clinical suspicion. Late diagnosis increases morbidity. We aimed to compare the usefulness of the 2011 International Consensus Diagnostic Criteria (ICDC) for Autoimmune Pancreatitis with the 2018 INSPPIRE (INternational Study Group of Pediatric Pancreatitis: In search for a cuRE) criteria. METHODS: We retrospectively analyzed demographics and clinical, laboratory, radiological, and histological findings at diagnosis and during long-term follow-up in children diagnosed with AIP in 2 tertiary hospitals between 2008 and 2021. RESULTS: We included 11 patients [6 girls; median age at diagnosis, 12.5 (range 2.8-15.7) years]. The most common symptom was abdominal pain. Pancreatic enzymes were elevated in 10 patients, and serum immunoglobulin G4 was elevated in 1. Magnetic resonance imaging showed enlargement of the pancreatic head in 10 patients and general pancreatic enlargement in 1. Pancreatic and papilla tissue were obtained from 9 patients. All patients received corticosteroids (prednisolone), and 4 also received azathioprine. According to the ICDC, all patients were classified as probable or non-otherwise specified AIP. According to INSPPIRE criteria, all patients were classified as AIP. Using the INSPPIRE criteria would have avoided biopsies in 6 patients who responded well to corticosteroids. CONCLUSIONS: The INSPPIRE criteria are useful. Using the ICDC in pediatric patients can delay diagnosis and result in unnecessary invasive tests.


Subject(s)
Autoimmune Diseases , Autoimmune Pancreatitis , Female , Humans , Child , Child, Preschool , Adolescent , Autoimmune Pancreatitis/diagnosis , Retrospective Studies , Autoimmune Diseases/diagnosis , Autoimmune Diseases/drug therapy , Diagnosis, Differential , Adrenal Cortex Hormones/therapeutic use
8.
Int J Vet Sci Med ; 11(1): 1-10, 2023.
Article in English | MEDLINE | ID: mdl-36632054

ABSTRACT

The lumbar nerve distribution can differ depending on vertebral count variations among individuals of the same species. The variation in the lumbar vertebra formula and the lumbar nerve distribution in twenty adult common opossums (eight female and twelve males) was studied. Radiographs were taken to confirm vertebral identification and count. Two vertebral patterns were recognized: three specimens presented five lumbar vertebrae (5VP) and seventeen individuals presented six lumbar vertebrae (6VP). All the 6VP specimens had the same innervation pattern; however, the 5PV had three different innervation patterns (5PVa, 5VPB, and 5PVc). 5VPa and 6VP differed only in the origin of the lateral femoral cutaneous nerve (L2-L3 and L3, respectively). The differences among 5PVa, 5PVb, and 5VPc were seen in the iliohypogastric nerve, which was formed by L1 in 5VPa and 5VPb, and T13 in 5VPc. The ilioinguinal nerve was formed by L1-L2 in 5VPa and 5VPb, while it was formed by T13-L1 in 5VPc. The genitofemoral nerve was formed by L2-L3 in 5VPa, L2 in 5VPb, and L1-L2 in 5VPc. The cutaneous femoris lateralis was formed by L2-L3 in 5VPa and 5VPc, while it is formed only by L2 in 5VPb. The femoral and obturator nerves were formed by L3-L4 in 5VPa, and L2-L3 in 5VPb and 5VPc. The lumbosacral trunk originated from L4-L5-S1 in 5VP and L5-L6-S1 in 6VP. The data provided in this study may help understand the relationship between the spine and lumbosacral plexus variations and may find application in veterinary spine surgery.

9.
Int J Mol Sci ; 23(22)2022 Nov 11.
Article in English | MEDLINE | ID: mdl-36430425

ABSTRACT

Antifolates such as methotrexate (MTX) have been largely known as anticancer agents because of their role in blocking nucleic acid synthesis and cell proliferation. Their mechanism of action lies in their ability to inhibit enzymes involved in the folic acid cycle, especially human dihydrofolate reductase (hDHFR). However, most of them have a classical structure that has proven ineffective against melanoma, and, therefore, inhibitors with a non-classical lipophilic structure are increasingly becoming an attractive alternative to circumvent this clinical resistance. In this study, we conducted a protocol combining virtual screening (VS) and cell-based assays to identify new potential non-classical hDHFR inhibitors. Among 173 hit compounds identified (average logP = 3.68; average MW = 378.34 Da), two-herein, called C1 and C2-exhibited activity against melanoma cell lines B16 and A375 by MTT and Trypan-Blue assays. C1 showed cell growth arrest (39% and 56%) and C2 showed potent cytotoxic activity (77% and 51%) in a dose-dependent manner. The effects of C2 on A375 cell viability were greater than MTX (98% vs 60%) at equivalent concentrations and times. Our results indicate that the integrated in silico/in vitro approach provided a benchmark to identify novel promising non-classical DHFR inhibitors showing activity against melanoma cells.


Subject(s)
Antineoplastic Agents , Folic Acid Antagonists , Melanoma , Humans , Folic Acid Antagonists/pharmacology , Folic Acid Antagonists/chemistry , Tetrahydrofolate Dehydrogenase/metabolism , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Melanoma/drug therapy , Methotrexate/pharmacology
10.
Sci Rep ; 12(1): 14030, 2022 08 18.
Article in English | MEDLINE | ID: mdl-35982147

ABSTRACT

As the world enters its second year of the pandemic caused by SARS-CoV-2, intense efforts have been directed to develop an effective diagnosis, prevention, and treatment strategies. One promising drug target to design COVID-19 treatments is the SARS-CoV-2 Mpro. To date, a comparative understanding of Mpro dynamic stereoelectronic interactions with either covalent or non-covalent inhibitors (depending on their interaction with a pocket called S1' or oxyanion hole) has not been still achieved. In this study, we seek to fill this knowledge gap using a cascade in silico protocol of docking, molecular dynamics simulations, and MM/PBSA in order to elucidate pharmacophore models for both types of inhibitors. After docking and MD analysis, a set of complex-based pharmacophore models was elucidated for covalent and non-covalent categories making use of the residue bonding point feature. The highest ranked models exhibited ROC-AUC values of 0.93 and 0.73, respectively for each category. Interestingly, we observed that the active site region of Mpro protein-ligand complex undergoes large conformational changes, especially within the S2 and S4 subsites. The results reported in this article may be helpful in virtual screening (VS) campaigns to guide the design and discovery of novel small-molecule therapeutic agents against SARS-CoV-2 Mpro protein.


Subject(s)
COVID-19 Drug Treatment , SARS-CoV-2 , Antiviral Agents/chemistry , Coronavirus 3C Proteases , Cysteine Endopeptidases/metabolism , Humans , Molecular Docking Simulation , Molecular Dynamics Simulation , Protease Inhibitors/chemistry
11.
Einstein (Sao Paulo) ; 20: eAO8013, 2022.
Article in English | MEDLINE | ID: mdl-35766673

ABSTRACT

OBJECTIVE: To determine the rate of complications associated with the use of temporary pacemakers in patients in the waiting list for the definitive pacemaker implantation in a public hospital located in São Paulo, SP, Brazil. METHODS: Retrospective observational study based on data extracted from medical records of patients admitted to Hospital Municipal Dr. Moyses Deutsch, Hospital Israelita Albert Einstein from January 2014 to December 2018. Patients aged 18 years or older, diagnosed with high degree atrioventricular block upon admission and with indications for definitive pacemaker implantation were included. All-cause mortality, clinical and surgical complications and length of hospital stay while waiting for the procedure were defined as primary outcomes. RESULTS: The sample comprised 66 patient allocated to one of two groups: with and without the need of temporary pacemaker while in hospital (n=45 and n=21, respectively). The rate of complications was higher in patients who used a temporary pacemaker (p<0.001). These included primarily pneumonia (p=0.048) and length of hospital stay (p=0.029). CONCLUSION: Patients who required a temporary pacemaker stayed longer in hospital. Longer hospital stay is associated with higher rates of general complications and all-cause mortality.


Subject(s)
Atrioventricular Block , Pacemaker, Artificial , Atrioventricular Block/diagnosis , Atrioventricular Block/therapy , Brazil , Humans , Length of Stay , Pacemaker, Artificial/adverse effects , Retrospective Studies , Treatment Outcome
13.
Eur J Radiol Open ; 9: 100400, 2022.
Article in English | MEDLINE | ID: mdl-35198656

ABSTRACT

PURPOSE: This study aims to determine if the presence of specific clinical and computed tomography (CT) patterns are associated with epidermal growth factor receptor (EGFR) mutation in patients with non-small cell lung cancer. METHODS: A systematic literature review and meta-analysis was carried out in 6 databases between January 2002 and July 2021. The relationship between clinical and CT patterns to detect EGFR mutation was measured and pooled using odds ratios (OR). These results were used to build several mathematical models to predict EGFR mutation. RESULTS: 34 retrospective diagnostic accuracy studies met the inclusion and exclusion criteria. The results showed that ground-glass opacities (GGO) have an OR of 1.86 (95%CI 1.34 -2.57), air bronchogram OR 1.60 (95%CI 1.38 - 1.85), vascular convergence OR 1.39 (95%CI 1.12 - 1.74), pleural retraction OR 1.99 (95%CI 1.72 - 2.31), spiculation OR 1.42 (95%CI 1.19 - 1.70), cavitation OR 0.70 (95%CI 0.57 - 0.86), early disease stage OR 1.58 (95%CI 1.14 - 2.18), non-smoker status OR 2.79 (95%CI 2.34 - 3.31), female gender OR 2.33 (95%CI 1.97 - 2.75). A mathematical model was built, including all clinical and CT patterns assessed, showing an area under the curve (AUC) of 0.81. CONCLUSIONS: GGO, air bronchogram, vascular convergence, pleural retraction, spiculated margins, early disease stage, female gender, and non-smoking status are significant risk factors for EGFR mutation. At the same time, cavitation is a protective factor for EGFR mutation. The mathematical model built acts as a good predictor for EGFR mutation in patients with lung adenocarcinoma.

14.
J Biomol Struct Dyn ; 40(19): 9030-9041, 2022.
Article in English | MEDLINE | ID: mdl-33949282

ABSTRACT

Cyclin-Dependent Kinase 2 (CDK2) and Vascular-Endothelial Growth Factor Receptor 2 (VEGFR2) are promising targets for the design of novel inhibitors in anticancer therapeutics. In a recent work, our group designed a set of potential dual inhibitors predicted to occupy an allosteric back pocket near the active site of both enzymes, but their dynamic and unbinding behavior was unclear. Here, we used molecular dynamics (MD) and metadynamics (meta-D) simulations to study two of these virtual candidates (herein called IQ2 and IQ3). Their binding mode was predicted to be similar to that observed in LQ5 and BAX, well-known back-pocket binders of CDK2 and VEGFR2, respectively, including H-bonding with critical residues such as Leu83/Cys113 and Asp145/Asp190 (but excepting H-bonding with Glu51/Glu111) in CDK2/VEGFR2, correspondingly. Likewise, while LQ5 and BAX unbound through the allosteric channel as expected for type-IIA inhibitors, IQ2 and IQ3 unbound via the ATP channel (except for CDK2-IQ2) as expected for type-I½A inhibitors. Interestingly, a C-C single/double bond difference between IQ2/IQ3, respectively, resulted associated with differences in the AS/T loop flexibility observed for CDK2. These insights will help developing scaffold modifications during an optimization stage, serving as a starting point to develop dual kinase inhibitors in challenging biological targets with a promising anticancer potential.Communicated by Ramaswamy H. Sarma.


Subject(s)
Molecular Dynamics Simulation , Cyclin-Dependent Kinase 2/chemistry , Protein Binding , Binding Sites
15.
Einstein (Säo Paulo) ; 20: eAO8013, 2022. tab
Article in English | LILACS-Express | LILACS | ID: biblio-1384792

ABSTRACT

ABSTRACT Objective To determine the rate of complications associated with the use of temporary pacemakers in patients in the waiting list for the definitive pacemaker implantation in a public hospital located in São Paulo, SP, Brazil. Methods Retrospective observational study based on data extracted from medical records of patients admitted to Hospital Municipal Dr. Moyses Deutsch, Hospital Israelita Albert Einstein from January 2014 to December 2018. Patients aged 18 years or older, diagnosed with high degree atrioventricular block upon admission and with indications for definitive pacemaker implantation were included. All-cause mortality, clinical and surgical complications and length of hospital stay while waiting for the procedure were defined as primary outcomes. Results The sample comprised 66 patient allocated to one of two groups: with and without the need of temporary pacemaker while in hospital (n=45 and n=21, respectively). The rate of complications was higher in patients who used a temporary pacemaker (p<0.001). These included primarily pneumonia (p=0.048) and length of hospital stay (p=0.029). Conclusion Patients who required a temporary pacemaker stayed longer in hospital. Longer hospital stay is associated with higher rates of general complications and all-cause mortality.

16.
Front Chem ; 9: 700802, 2021.
Article in English | MEDLINE | ID: mdl-34422762

ABSTRACT

Fragment-based drug design (FBDD) and pharmacophore modeling have proven to be efficient tools to discover novel drugs. However, these approaches may become limited if the collection of fragments is highly repetitive, poorly diverse, or excessively simple. In this article, combining pharmacophore modeling and a non-classical type of fragmentation (herein called non-extensive) to screen a natural product (NP) library may provide fragments predicted as potent, diverse, and developable. Initially, we applied retrosynthetic combinatorial analysis procedure (RECAP) rules in two versions, extensive and non-extensive, in order to deconstruct a virtual library of NPs formed by the databases Traditional Chinese Medicine (TCM), AfroDb (African Medicinal Plants database), NuBBE (Nuclei of Bioassays, Biosynthesis, and Ecophysiology of Natural Products), and UEFS (Universidade Estadual de Feira de Santana). We then developed a virtual screening (VS) using two groups of natural-product-derived fragments (extensive and non-extensive NPDFs) and two overlapping pharmacophore models for each of 20 different proteins of therapeutic interest. Molecular weight, lipophilicity, and molecular complexity were estimated and compared for both types of NPDFs (and their original NPs) before and after the VS proceedings. As a result, we found that non-extensive NPDFs exhibited a much higher number of chemical entities compared to extensive NPDFs (45,355 vs. 11,525 compounds), accounting for the larger part of the hits recovered and being far less repetitive than extensive NPDFs. The structural diversity of both types of NPDFs and the NPs was shown to diminish slightly after VS procedures. Finally, and most interestingly, the pharmacophore fit score of the non-extensive NPDFs proved to be not only higher, on average, than extensive NPDFs (56% of cases) but also higher than their original NPs (69% of cases) when all of them were also recognized as hits after the VS. The findings obtained in this study indicated that the proposed cascade approach was useful to enhance the probability of identifying innovative chemical scaffolds, which deserve further development to become drug-sized candidate compounds. We consider that the knowledge about the deconstruction degree required to produce NPDFs of interest represents a good starting point for eventual synthesis, characterization, and biological activity studies.

17.
J Appl Res Intellect Disabil ; 34(3): 830-839, 2021 May.
Article in English | MEDLINE | ID: mdl-33538083

ABSTRACT

BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and autism spectrum disorder (ASD). In Colombia, there are no screening or testing protocols established for the diagnosis of FXS. In this study, we aimed to describe the diagnostic trends of FXS in Colombia. METHODS: Data were included on 1322 individuals obtained based on data from the only 2 databases available. Sociodemographic information and data related to the diagnostic process were obtained and included in this study. RESULTS: The average age at the time of diagnosis for individuals with the full mutation (FM) was of 26.9 ± 2.57 years and was strongly dependent on sex and socioeconomic status. Most individuals with a molecular diagnosis were from the main cities. CONCLUSION: The overall age of diagnosis of FXS is later in life than reports from other countries. Restricted access to molecular testing through the national health system might explain this discrepancy in Colombia.


Subject(s)
Autism Spectrum Disorder , Fragile X Syndrome , Intellectual Disability , Alleles , Colombia/epidemiology , Fragile X Mental Retardation Protein/genetics , Fragile X Syndrome/diagnosis , Fragile X Syndrome/epidemiology , Fragile X Syndrome/genetics , Humans , Intellectual Disability/diagnosis , Intellectual Disability/epidemiology , Intellectual Disability/genetics
18.
J Biomol Struct Dyn ; 39(9): 3285-3299, 2021 Jun.
Article in English | MEDLINE | ID: mdl-32362218

ABSTRACT

Cyclin-Dependent Kinase 2 (CDK2) and Vascular Endothelial Growth Factor Receptor (VEGFR2) have largely been considered as attractive targets for developing anticancer agents. However, there is no dual inhibitor commercially available in the market that interacts simultaneously with the allosteric back pocket of these enzymes. We applied a combined computational strategy that started with the generation of two overlapping pharmacophore models of both kinases at 'inactive' conformation. Next, several virtual libraries of natural products, including the databases TCM (Traditional Chinese Medicine), UEFS (Universidade Estadual de Feira de Santana), NuBBE (Nuclei of Bioassays, Biosynthesis, and Ecophysiology of Natural Products) and AfroDb (African Medicinal Plants Database) were deconstructed using a non-extensive version of the approach RECAP (retrosynthetic combinatorial analysis procedure). These natural-product-derived fragments (NPDFs) were screened and merged into drug-sized compounds, which were filtered by Lipinski's Rule-of-five (Ro5) and docking. As a result, two pharmacophore models, namely Hypo1 and Hypo2, were developed with an accuracy of 0.94 and 0.84, respectively. Deconstruction of natural products produced a set of 16655 unique non-extensive NPDFs that were screened against both pharmacophore models. Finally, after merging, Ro5-filtering and docking, we obtained a set of 20 hit compounds predicted to be diverse, developable, synthesizable and potent. The computational strategy proved successful to find virtual candidates of kinase inhibitors and therefore contributes to the identification of innovative multi-target compounds with potential anticancer activity. Communicated by Ramaswamy H. Sarma.


Subject(s)
Antineoplastic Agents , Biological Products , Cyclin-Dependent Kinase 2/antagonists & inhibitors , Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors , Molecular Docking Simulation
19.
Int J Psychol Res (Medellin) ; 13(2): 109-117, 2020.
Article in English | MEDLINE | ID: mdl-33329883

ABSTRACT

This theoretical paper depicts the clinics of work as a subdisciplinary and interdisciplinary field of the social psychology of work and organizations, interested in analyzing and intervening from a critical-clinical perspective in the subjectivity-work-context relationship, in the context of discomfort, suffering, and pleasure, and thus, in the mental health within this field. Consequently, it separates from traditional occupational health, which ignores subjective singularities. The subdiscipline of CW develops the determinants of pleasure, discomfort, and suffering at work, standing out in the process as a possible alternative of occupational health, based on research practice and intervention from a critical perspective.


Este artículo teórico presenta las clínicas del trabajo como campo subdisciplinar e interdisciplinar de la psicología social de las organizaciones y del trabajo, interesado en analizar e intervenir desde una perspectiva clínico-crítica sobre las relaciones subjetividad-trabajo-contexto, en clave de malestar, sufrimiento y placer, y, por ende, en la salud mental en este campo, deslindado de la salud ocupacional tradicional que se aleja de la singularidad subjetiva. Se desarrollan los determinantes del placer, el malestar y el sufrimiento en el trabajo y subraya desde la perspectiva crítica cómo puede ser una alternativa posible a la salud ocupacional como práctica investigativa y de intervención.

20.
Int. j. morphol ; 38(4): 853-856, Aug. 2020. graf
Article in Spanish | LILACS | ID: biblio-1124865

ABSTRACT

La arteria recurrente radial nace en el extremo proximal de la arteria radial y desde ahí asciende oblicuamente para anastomosarse con la arteria colateral radial, entregando en ese trayecto una serie de ramas para los músculos cercanos. Dicha arteria junto con sus ramas fueron descritas (por su importancia en abordajes quirúrgicos) por Arnold K. Henry como "the radial leash". Actualmente en clínica se utiliza el nombre "leash of Henry" para referirse a una o más ramas musculares de la arteria recurrente radial, sobretodo cuando cuando se encuentran en relación con el ramo profundo del nervio radial, pudiendo llegar a causar compresiones de dicho nervio en algunos casos. Se realizó una descripción de caso de una leash of Henry atípica, encontrada en una muestra cadavérica del laboratorio de anatomía de la Universidad Católica del Maule, de sexo masculino y nacionalidad chilena. La arteria encontrada corresponde a la rama de mayor calibre de la arteria recurrente radial, que se dirige directamente al músculo extensor de los dedos, dibujando un trayecto horizontal y cruzando por anterior al ramo profundo del nervio radial. Esta hallazgo difere a lo descrito por Henry y otros autores más recientes, y por lo tanto aporta información potencialmente útil a la hora de realizar procedimientos quirúrgicos que requieran un abordaje posterior o lateral de la cabeza del radio, como también descompresiones del nervio radial en esta zona.


The radial recurrent artery originates at the proximal end of the radial artery and from there ascends obliquely to anastomosing with the radial collateral artery. It gives off several branches for nearby muscles on its path. This artery along with its branches were described (due to its importance in surgical approaches) by Arnold K. Henry as "the radial leash". Currently, in clinical terms, the name "Leash of Henry" is used to refer to one or more muscular branches of the radial recurrent artery, especially when they are in relation to the deep branch of the radial nerve, and may cause compression of the nerve in some cases. A case description of an atypical Leash of Henry was found, found in a Chilean, male cadaveric sample of the anatomy laboratory, Universidad Católica del Maule. The artery corresponds to the branch of greater caliber of the recurrent radial artery, which goes directly to the extensor digitorum muscle. It draws a horizontal path and crosses the deep branch of the radial nerve anteriorly. This finding differs from what was described by Henry and other more recent authors. Therefore, this is potentially useful information when performing surgical procedures that require a posterior or lateral approach to the radius head, as well as radial nerve decompressions in this area.


Subject(s)
Humans , Male , Middle Aged , Radial Nerve/anatomy & histology , Radial Artery/anatomy & histology , Elbow/anatomy & histology , Cadaver , Elbow/innervation , Elbow/blood supply , Anatomic Variation
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