Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 108
Filter
Add more filters

Publication year range
1.
Int J Mol Sci ; 25(7)2024 Apr 06.
Article in English | MEDLINE | ID: mdl-38612895

ABSTRACT

Expression of miR-21 has been found to be altered in almost all types of cancers, and it has been classified as an oncogenic microRNA. In addition, the expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study, we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells, there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3'-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed, and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.


Subject(s)
MicroRNAs , Uterine Cervical Neoplasms , Female , Humans , Uterine Cervical Neoplasms/genetics , Signal Transduction , Cell Proliferation/genetics , Cell Movement/genetics , RNA, Small Interfering , MicroRNAs/genetics , Psychomotor Agitation , RNA, Double-Stranded , GPI-Linked Proteins/genetics
2.
Planta ; 258(1): 20, 2023 Jun 16.
Article in English | MEDLINE | ID: mdl-37326881

ABSTRACT

MAIN CONCLUSION: SA and H2O2, in single and mixed elicitation stimulate specialized metabolism and activate oxidative stress in C. tenuiflora plants. Single elicitation with salicylic acid (SA at 75 µM) and, hydrogen peroxide (at 150 µM), and mixed elicitation (75 µM SA + 150 µM H2O2) were evaluated on specialized metabolism in Castilleja tenuiflora Benth. plants. Total phenolic content (TPC), phenylalanine ammonia-lyase (PAL) activity, antioxidant enzymes and specialized metabolite profiles, as well as the expression levels of eight genes involved in phenolic (Cte-TyrDC, Cte-GOT2, Cte-ADD, Cte-AO3, Cte-PAL1, Cte-CHS1) and terpene pathways (Cte-DXS1 and Cte-G10H) and their correlation with major metabolite (verbascoside and aucubin) concentrations were investigated. TPC content (three-fold) and PAL activity (11.5-fold) increased with mixed elicitation, as well as catalase and peroxidase activity (11.3-fold and 10.8-fold, respectively), compared to single elicitation. Phenylethanoid accumulation was greatest under mixed elicitation, followed by SA and H2O2. Lignan accumulation was differential, depending on the plant part and the elicitor. Flavonoids only appeared after mixed elicitation. The high concentration of verbascoside under mixed elicitation was related to a high gene expression. Single elicitation induced iridoid accumulation in specific parts (H2O2 in aerial parts and SA in roots), whereas under mixed elicitation, it accumulated in both parts. A high concentration of aucubin in the aerial part was related to a high expression level of genes of the terpene pathway Cte-DXS1 and Cte-G10H, and in the root with Cte-G10H, while Cte-DXS1 was downregulated in this tissue in all treatments. Mixed elicitation with SA and H2O2 represents an interesting tool to increase the production of specialized metabolites in plants.


Subject(s)
Hydrogen Peroxide , Orobanchaceae , Hydrogen Peroxide/metabolism , Salicylic Acid/metabolism , Iridoids , Phenols/metabolism , Antioxidants/metabolism , Orobanchaceae/metabolism
3.
BMC Med Educ ; 23(1): 975, 2023 Dec 19.
Article in English | MEDLINE | ID: mdl-38115060

ABSTRACT

BACKGROUND: The dentist should have a thorough knowledge of the science, protocols and procedures for dental shade selection in order to mimic dental tissue with restorative materials, respecting the individual needs and attitudes of each patient and providing them with a pleasant and esthetically acceptable appearance. The present study evaluated the knowledge and attitudes of dental interns from two Peruvian universities about dental shade selection and its relationship with sociodemographic factors. METHODS: The present cross-sectional and analytical study was carried out on Peruvian dental interns from the Universidad Nacional Federico Villarreal and the Universidad Privada de San Juan Bautista during May to June 2022. Two validated questionnaires on knowledge and attitudes about dental shade selection were used. A Poisson regression model with robust variance using the adjusted prevalence ratio (APR) was used to assess the influence of the variables: age group, sex, place of origin and type of university, considering a significance level of p<0.05. RESULTS: The results showed that 40.8% (95% CI: 34.0% - 47.6%) of the interns presented unfavorable attitudes while 90.1% (95% CI: 86.0% - 94.2%) presented insufficient knowledge. It was also found that dental interns under 29 years of age were 32% less likely to have unfavorable attitudes (APR = 0.68, 95% CI 0.48 - 0.96) and 11% more likely to have insufficient knowledge (APR = 1.11, 95% CI 1.01 - 1.24) about tooth shade selection compared to dental interns aged 29 years and older. Finally, women were 55% more likely to have unfavorable attitudes about tooth shade selection compared to men (APR = 1.55; 95% CI: 1.08 - 2.22). CONCLUSION: The majority of dental interns presented insufficient knowledge and less than half had unfavorable attitudes about dental shade selection. In addition, being a student under 29 years of age was a risk factor for presenting insufficient knowledge and at the same time constituted a protective factor for presenting unfavorable attitudes. Likewise, being a female student was a risk factor for presenting unfavorable attitudes about dental shade selection.


Subject(s)
Sociodemographic Factors , Students, Dental , Male , Humans , Female , Adult , Color , Cross-Sectional Studies , Peru
4.
Int J Mol Sci ; 24(18)2023 Sep 16.
Article in English | MEDLINE | ID: mdl-37762475

ABSTRACT

Stressed organisms identify intracellular molecules released from damaged cells due to trauma or pathogen infection as components of the innate immune response. These molecules called DAMPs (Damage-Associated Molecular Patterns) are extracellular ATP, sugars, and extracellular DNA, among others. Animals and plants can recognize their own DNA applied externally (self-exDNA) as a DAMP with a high degree of specificity. However, little is known about the microalgae responses to damage when exposed to DAMPs and specifically to self-exDNAs. Here we compared the response of the oilseed microalgae Neochloris oleoabundans to self-exDNA, with the stress responses elicited by nonself-exDNA, methyl jasmonate (MeJA) and sodium bicarbonate (NaHCO3). We analyzed the peroxidase enzyme activity related to the production of reactive oxygen species (ROS), as well as the production of polyphenols, lipids, triacylglycerols, and phytohormones. After 5 min of addition, self-exDNA induced peroxidase enzyme activity higher than the other elicitors. Polyphenols and lipids were increased by self-exDNA at 48 and 24 h, respectively. Triacylglycerols were increased with all elicitors from addition and up to 48 h, except with nonself-exDNA. Regarding phytohormones, self-exDNA and MeJA increased gibberellic acid, isopentenyladenine, and benzylaminopurine at 24 h. Results show that Neochloris oleoabundans have self-exDNA specific responses.


Subject(s)
Chlorophyceae , Microalgae , Animals , Plant Growth Regulators , Peroxidase , Alarmins , Coloring Agents , DNA , Oxylipins , Peroxidases
5.
Int J Mol Sci ; 25(1)2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38203628

ABSTRACT

Psittacanthus calyculatus parasitizes mesquite trees through a specialized structure called a haustorium, which, in the intrusive process, can cause cellular damage in the host tree and release DAMPs, such as ATP, sugars, RNA, and DNA. These are highly conserved molecules that primarily function as signals that trigger and activate the defense responses. In the present study, we generate extracellular DNA (exDNA) from mesquite (P. laevigata) tree leaves (self-exDNA) and P. calyculatus (non-self exDNA) mistletoe as DAMP sources to examine mesquite trees' capacity to identify specific self or non-self exDNA. We determined that mesquite trees perceive self- and non-self exDNA with the synthesis of O2•-, H2O2, flavonoids, ROS-enzymes system, MAPKs activation, spatial concentrations of JA, SA, ABA, and CKs, and auxins. Our data indicate that self and non-self exDNA application differs in oxidative burst, JA signaling, MAPK gene expression, and scavenger systems. This is the first study to examine the molecular biochemistry effects in a host tree using exDNA sources derived from a mistletoe.


Subject(s)
Mistletoe , Prosopis , Alarmins , DNA , Hydrogen Peroxide , Trees
6.
Ann Hum Biol ; 49(7-8): 291-298, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36350847

ABSTRACT

BACKGROUND: Plasminogen activator inhibitor 1 (PAI-1) and resistin are associated with dysfunctional adipose tissue (AT)-related metabolic complications. The role of dietary eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids in this relationship is unknown. AIM: To investigate the association of EPA and DHA with PAI-1 and resistin, as well as the role of this association on the glucose metabolism of apparently healthy subjects. SUBJECTS AND METHODS: Thirty-six healthy individuals were included. Validated food frequency questionnaires were used to analyse dietary habits. Inflammatory and glucose metabolism markers were quantified. Subcutaneous AT samples were obtained, and adipocyte number, area, and macrophage content were assessed. RESULTS: In 36 subjects aged 56 ± 8 years and with a body mass index of 26 ± 4 kg/m2, logEPA, and logDHA showed significant association with logresistin and a marginal association with PAI-1. Adipocyte number, area, and lognumber of macrophages per adipocyte significantly correlated with PAI-1 but not with logresistin. Although logEPA and logDHA were independently associated with loginsulin, loginsulin resistance, and C-Peptide, the addition of logresistin, but not of PAI-1, into the multivariable model, abolished the associations. CONCLUSIONS: EPA and DHA could modulate glucose metabolism across AT functional states. Our data indicate that this association is independent of other metabolic risk factors.


Subject(s)
Fatty Acids, Omega-3 , Plasminogen Activator Inhibitor 1 , Humans , Plasminogen Activator Inhibitor 1/metabolism , Resistin/metabolism , Eicosapentaenoic Acid/metabolism , Eicosapentaenoic Acid/pharmacology , Self Report , Healthy Volunteers , Docosahexaenoic Acids/metabolism , Docosahexaenoic Acids/pharmacology , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-3/pharmacology , Adipose Tissue/metabolism , Glucose/metabolism
7.
Biochem J ; 477(18): 3599-3612, 2020 09 30.
Article in English | MEDLINE | ID: mdl-32869839

ABSTRACT

Among the major challenges in the development of biopharmaceuticals are structural heterogeneity and aggregation. The development of a successful therapeutic monoclonal antibody (mAb) requires both a highly active and also stable molecule. Whilst a range of experimental (biophysical) approaches exist to track changes in stability of proteins, routine prediction of stability remains challenging. The fluorescence red edge excitation shift (REES) phenomenon is sensitive to a range of changes in protein structure. Based on recent work, we have found that quantifying the REES effect is extremely sensitive to changes in protein conformational state and dynamics. Given the extreme sensitivity, potentially this tool could provide a 'fingerprint' of the structure and stability of a protein. Such a tool would be useful in the discovery and development of biopharamceuticals and so we have explored our hypothesis with a panel of therapeutic mAbs. We demonstrate that the quantified REES data show remarkable sensitivity, being able to discern between structurally identical antibodies and showing sensitivity to unfolding and aggregation. The approach works across a broad concentration range (µg-mg/ml) and is highly consistent. We show that the approach can be applied alongside traditional characterisation testing within the context of a forced degradation study (FDS). Most importantly, we demonstrate the approach is able to predict the stability of mAbs both in the short (hours), medium (days) and long-term (months). The quantified REES data will find immediate use in the biopharmaceutical industry in quality assurance, formulation and development. The approach benefits from low technical complexity, is rapid and uses instrumentation which exists in most biochemistry laboratories without modification.


Subject(s)
Antibodies, Monoclonal/chemistry , Protein Conformation , Protein Stability , Spectrometry, Fluorescence
8.
Biol Blood Marrow Transplant ; 26(6): e135-e137, 2020 06.
Article in English | MEDLINE | ID: mdl-32070723

ABSTRACT

Telehealth involves the use of telecommunication and information technology for the delivery of clinical care and may be a mechanism to alleviate the burden of visits faced by patients undergoing hematopoietic cell transplantation (HCT). Few studies have evaluated the feasibility and acceptability of telehealth visits in the care of HCT patients. We conducted 27 telehealth visits with 25 patients undergoing HCT using a videoconferencing system that allows for real-time, 2-way interactions and administered satisfaction surveys to patients and providers. Of the 25 patients included in the study, 20 (80%) and 5 (20%) were undergoing autologous and allogeneic HCT, respectively. The telehealth visits were distributed as follows: 3 inpatient visits upon admission for HCT; 11 inpatient visits between 2 and 14 days post-HCT; 4 inpatient visits prior to discharge after HCT; 8 outpatient, post-HCT follow-up visits; and 1 handoff to a community oncologist. Out of a total of 54 provider assessments, 7 providers (13%) were unable to complete some part of the physical examination, but no provider reported being unable to manage patients' symptoms through telehealth. Eighty-one percent of patients were either satisfied or very satisfied with the telemedicine session. Overall satisfaction was higher among patients than providers (mean scores 4.12 versus 2.64; scale 1 to 5, with 1 = very poor to 5 = excellent). Technological barriers resulting in delays and suboptimal physical examination were largely responsible for provider dissatisfaction. The use of telehealth to deliver comprehensive follow-up care to HCT patients is feasible across different HCT types but is dependent upon quality of data streaming and videoconferencing technologies.


Subject(s)
Hematopoietic Stem Cell Transplantation , Telemedicine , Humans , Pilot Projects , Surveys and Questionnaires , Videoconferencing
9.
Rev Chil Pediatr ; 90(4): 411-421, 2019 Aug.
Article in English, Spanish | MEDLINE | ID: mdl-31859714

ABSTRACT

OBJECTIVE: To evaluate the impact of a community program aimed at improving the children mal nutrition in a rural community of the State of Chiapas, Mexico, 2013. MATERIAL AND METHOD: Des criptive study of the evaluation program from a secondary database of nutritional data registry of 113 children under five years of age in a rural area of Mexico. The intervention and the survey were carried out during 2013. Baseline and 4-month measurements were recorded. The World Health Organization (WHO) Anthro software was used to calculate nutritional status indicators. According to WHO guidelines, the following data were estimated: weight for age (W/A), height for age (H/A), weight for height (W/H), and Body mass index for age (BMI/A). Position and dispersion measures were calculated; Student's T-test, Kruskal-Wallis, and MacNemar test were used for paired data and linear regression. RESULTS: Between the beginning and the end, the median of the Z W/H went from -0.7 (p25 -1.24, p75 -0.01) to -0.62 (p25 -1.09, p75 -0.15). The prevalence of low weight decreased from 5.31% (CI 2.38-11.44) to 4.42% (CI 1.83-10.32) (Z BMI/A). The appropriate weight according to Z score W/H increased from 78.76% (CI 70.12-85.43) to 84.96% (76.98-90.51). In the subgroup with low initial weight, the mean of Z BMI/A and Z W/H increased 0.4 (p = 0.003). The change in the mean of Z W/H was 0.02 points in the subgroup that received the direct transfer program and of -0.3 in which it did not (p = 0.020). CONCLUSIONS: It is concluded that the community program during the four months of implementation contributed to improve some anthropometric indicators, although no apparent effects were found in indicators related to chronic malnutrition.


Subject(s)
Child Nutrition Disorders/therapy , Community Health Services/organization & administration , Nutritional Status , Rural Population , Anthropometry , Body Height , Body Mass Index , Body Weight , Child Nutrition Disorders/epidemiology , Child, Preschool , Female , Humans , Infant , Longitudinal Studies , Male , Mexico , Prevalence
10.
Entropy (Basel) ; 20(1)2018 Jan 11.
Article in English | MEDLINE | ID: mdl-33265130

ABSTRACT

We calculate the transverse velocity fluctuations correlation function of a linear and homogeneous viscoelastic liquid by using a generalized Langevin equation (GLE) approach. We consider a long-ranged (power-law) viscoelastic memory and a noise with a long-range (power-law) auto-correlation. We first evaluate the transverse velocity fluctuations correlation function for conventional time derivatives C ^ N F ( k → , t ) and then introduce time fractional derivatives in their equations of motion and calculate the corresponding fractional correlation function. We find that the magnitude of the fractional correlation C ^ F ( k → , t ) is always lower than the non-fractional one and decays more rapidly. The relationship between the fractional loss modulus G F ″ ( ω ) and C ^ F ( k → , t ) is also calculated analytically. The difference between the values of G ″ ( ω ) for two specific viscoelastic fluids is quantified. Our model calculation shows that the fractional effects on this measurable quantity may be three times as large as compared with its non-fractional value. The fact that the dynamic shear modulus is related to the light scattering spectrum suggests that the measurement of this property might be used as a suitable test to assess the effects of temporal fractional derivatives on a measurable property. Finally, we summarize the main results of our approach and emphasize that the eventual validity of our model calculations can only come from experimentation.

11.
J Biol Chem ; 290(4): 2334-50, 2015 Jan 23.
Article in English | MEDLINE | ID: mdl-25488663

ABSTRACT

The solution structure of complement C3b is crucial for the understanding of complement activation and regulation. C3b is generated by the removal of C3a from C3. Hydrolysis of the C3 thioester produces C3u, an analog of C3b. C3b cleavage results in C3c and C3d (thioester-containing domain; TED). To resolve functional questions in relation to C3b and C3u, analytical ultracentrifugation and x-ray and neutron scattering studies were used with C3, C3b, C3u, C3c, and C3d, using the wild-type allotype with Arg(102). In 50 mm NaCl buffer, atomistic scattering modeling showed that both C3b and C3u adopted a compact structure, similar to the C3b crystal structure in which its TED and macroglobulin 1 (MG1) domains were connected through the Arg(102)-Glu(1032) salt bridge. In physiological 137 mm NaCl, scattering modeling showed that C3b and C3u were both extended in structure, with the TED and MG1 domains now separated by up to 6 nm. The importance of the Arg(102)-Glu(1032) salt bridge was determined using surface plasmon resonance to monitor the binding of wild-type C3d(E1032) and mutant C3d(A1032) to immobilized C3c. The mutant did not bind, whereas the wild-type form did. The high conformational variability of TED in C3b in physiological buffer showed that C3b is more reactive than previously thought. Because the Arg(102)-Glu(1032) salt bridge is essential for the C3b-Factor H complex during the regulatory control of C3b, the known clinical associations of the major C3S (Arg(102)) and disease-linked C3F (Gly(102)) allotypes of C3b were experimentally explained for the first time.


Subject(s)
Complement Activation , Complement C3/metabolism , Complement C3b/metabolism , Complement C3c/metabolism , Complement C3d/metabolism , Arginine/chemistry , Crystallography, X-Ray , Humans , Macroglobulins/metabolism , Mutagenesis , Mutation , Protein Conformation , Protein Multimerization , Scattering, Radiation , Surface Plasmon Resonance , Ultracentrifugation
12.
J Biol Chem ; 288(26): 19197-210, 2013 Jun 28.
Article in English | MEDLINE | ID: mdl-23661701

ABSTRACT

The sub-retinal pigment epithelial deposits that are a hallmark of age-related macular degeneration contain both C3b and millimolar levels of zinc. C3 is the central protein of complement, whereas C3u is formed by the spontaneous hydrolysis of the thioester bridge in C3. During activation, C3 is cleaved to form active C3b, then C3b is inactivated by Factor I and Factor H to form the C3c and C3d fragments. The interaction of zinc with C3 was quantified using analytical ultracentrifugation and x-ray scattering. C3, C3u, and C3b associated strongly in >100 µM zinc, whereas C3c and C3d showed weak association. With zinc, C3 forms soluble oligomers, whereas C3u and C3b precipitate. We conclude that the C3, C3u, and C3b association with zinc depended on the relative positions of C3d and C3c in each protein. Computational predictions showed that putative weak zinc binding sites with different capacities exist in all five proteins, in agreement with experiments. Factor H forms large oligomers in >10 µM zinc. In contrast to C3b or Factor H alone, the solubility of the central C3b-Factor H complex was much reduced at 60 µM zinc and even more so at >100 µM zinc. The removal of the C3b-Factor H complex by zinc explains the reduced C3u/C3b inactivation rates by zinc. Zinc-induced precipitation may contribute to the initial development of sub-retinal pigment epithelial deposits in the retina as well as reducing the progression to advanced age-related macular degeneration in higher risk patients.


Subject(s)
Complement C3b/metabolism , Complement Factor H/metabolism , Inflammation/metabolism , Macular Degeneration/metabolism , Retinal Pigment Epithelium/metabolism , Zinc/pharmacology , Binding Sites , Computer Simulation , Epithelial Cells/cytology , Humans , Models, Molecular , Protein Binding , Protein Conformation , Retina/metabolism , Scattering, Radiation , Ultracentrifugation , X-Rays , Zinc/chemistry
13.
J Biol Chem ; 288(39): 27737-51, 2013 Sep 27.
Article in English | MEDLINE | ID: mdl-23921391

ABSTRACT

The highly sulfated polysaccharides heparin and heparan sulfate (HS) play key roles in the regulation of physiological and pathophysiological processes. Despite its importance, no molecular structures of free HS have been reported up to now. By combining analytical ultracentrifugation, small angle x-ray scattering, and constrained scattering modeling recently used for heparin, we have analyzed the solution structures for eight purified HS fragments dp6-dp24 corresponding to the predominantly unsulfated GlcA-GlcNAc domains of heparan sulfate. Unlike heparin, the sedimentation coefficient s20,w of HS dp6-dp24 showed a small rotor speed dependence, where similar s20,w values of 0.82-1.26 S (absorbance optics) and 1.05-1.34 S (interference optics) were determined. The corresponding x-ray scattering measurements of HS dp6-dp24 gave radii of gyration RG values from 1.03 to 2.82 nm, cross-sectional radii of gyration RXS values from 0.31 to 0.65 nm, and maximum lengths L from 3.0 to 10.0 nm. These data showed that HS has a longer and more bent structure than heparin. Constrained scattering modeling starting from 5,000 to 12,000 conformationally randomized HS structures gave best fit dp6-dp24 molecular structures that were longer and more bent than their equivalents in heparin. Alternative fits were obtained for HS dp18 and dp24, indicating their higher bending and flexibility. We conclude that HS displays bent conformations that are significantly distinct from that for heparin. The difference is attributed to the different predominant monosaccharide sequence and reduced sulfation of HS, indicating that HS may interact differently with proteins compared with heparin.


Subject(s)
Heparitin Sulfate/chemistry , Crystallization , Glycosides/chemistry , Heparin/chemistry , Ligands , Models, Molecular , Scattering, Radiation , Synchrotrons , Ultracentrifugation , X-Rays
14.
Neurotoxicol Teratol ; 102: 107338, 2024.
Article in English | MEDLINE | ID: mdl-38431065

ABSTRACT

BACKGROUND: Prenatal exposure to secondhand (environmental) tobacco smoke (SHS) is associated with adverse neurodevelopmental outcomes, including altered functional activation of cognitive control brain circuitry and increased attention problems in children. Exposure to SHS is more common among Black youth who are also disproportionately exposed to socioeconomic disadvantage and concomitant maternal distress. We examine the combined effects of exposure to prenatal SHS and postnatal maternal distress on the global efficiency (GE) of the brain's cingulo-opercular (CO) and fronto-parietal control (FP) networks in childhood, as well as associated attention problems. METHODS: Thirty-two children of non-smoking mothers followed in a prospective longitudinal birth cohort at the Columbia Center for Children's Environmental Health (CCCEH) completed magnetic resonance imaging (MRI) at ages 7-9 years old. GE scores were extracted from general connectivity data collected while children completed the Simon Spatial Incompatibility functional magnetic resonance imaging (fMRI) task. Prenatal SHS was measured using maternal urinary cotinine from the third trimester; postnatal maternal distress was assessed at child age 5 using the Psychiatric Epidemiology Research Interview (PERI-D). The Child Behavior Checklist (CBCL) measured Attention and Attention Deficit Hyperactivity Disorder (ADHD) problems at ages 7-9. Linear regressions examined the interaction between prenatal SHS and postnatal maternal distress on the GE of the CO or FP networks, as well as associations between exposure-related network alterations and attention problems. All models controlled for age, sex, maternal education at prenatal visit, race/ethnicity, global brain correlation, and mean head motion. RESULTS: The prenatal SHS by postnatal maternal distress interaction term associated with the GE of the CO network (ß = 0.673, Bu = 0.042, t(22) = 2.427, p = .024, D = 1.42, 95% CI [0.006, 0.079], but not the FP network (ß = 0.138, Bu = 0.006, t(22) = 0.434, p = .668, 95% CI [-0.022, 0.033]). Higher GE of the CO network was associated with more attention problems (ß = 0.472, Bu = 43.076, t(23) = 2.780, p = .011, D = 1.74, n = 31, 95% CI [11.024, 75.128], n = 31) and ADHD risk (ß = 0.436, Bu = 21.961, t(29) = 2.567, p = .018, D = 1.81, 95% CI [4.219, 39.703], n = 30). CONCLUSIONS: These preliminary findings suggest that sequential prenatal SHS exposure and postnatal maternal distress could alter the efficiency of the CO network and increase risk for downstream attention problems and ADHD. These findings are consistent with prior studies showing that prenatal SHS exposure is associated with altered function of brain regions that support cognitive control and with ADHD problems. Our model also identifies postnatal maternal distress as a significant moderator of this association. These data highlight the combined neurotoxic effects of exposure to prenatal SHS and postnatal maternal distress. Critically, such exposures are disproportionately distributed among youth from minoritized groups, pointing to potential pathways to known mental health disparities.


Subject(s)
Attention Deficit Disorder with Hyperactivity , Prenatal Exposure Delayed Effects , Tobacco Smoke Pollution , Child , Female , Pregnancy , Adolescent , Humans , Child, Preschool , Tobacco Smoke Pollution/adverse effects , Prospective Studies , Attention Deficit Disorder with Hyperactivity/etiology , Attention Deficit Disorder with Hyperactivity/psychology , Mothers , Cotinine , Prenatal Exposure Delayed Effects/chemically induced
15.
ChemMedChem ; 19(7): e202300548, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38381042

ABSTRACT

Several novel chemical series were identified that modulate glucocerebrosidase (GCase). Compounds from these series are active on glucosylceramide, unlike other known GCase modulators. We obtained GCase crystal structures with two compounds that have distinct chemotypes. Positive allosteric modulators bind to a site on GCase and induce conformational changes, but also induce an equilibrium state between monomer and dimer.


Subject(s)
Gaucher Disease , Glucosylceramidase , Humans , Glucosylceramidase/chemistry , Glucosylceramidase/metabolism , Glucosylceramides , Hydrolysis , Gaucher Disease/drug therapy
16.
Plants (Basel) ; 13(7)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38611495

ABSTRACT

Hamelia patens (Rubiaceae), known as firebush, is a source of bioactive monoterpenoid oxindole alkaloids (MOAs) derived from monoterpenoid indole alkaloids (MIAs). With the aim of understanding the regulation of the biosynthesis of these specialized metabolites, micropropagated plants were elicited with jasmonic acid (JA) and salicylic acid (SA). The MOA production and MIA biosynthetic-related gene expression were evaluated over time. The production of MOAs was increased compared to the control up to 2-fold (41.3 mg g DW-1) at 72 h in JA-elicited plants and 2.5-fold (42.4 mg g DW-1) at 120 h in plants elicited with SA. The increment concurs with the increase in the expression levels of the genes HpaLAMT, HpaTDC, HpaSTR, HpaNPF2.9, HpaTHAS1, and HpaTHAS2. Interestingly, it was found that HpaSGD was downregulated in both treatments after 24 h but in the SA treatment at 120 h only was upregulated to 8-fold compared to the control. In this work, we present the results of MOA production in H. patens and discuss how JA and SA might be regulating the central biosynthetic steps that involve HpaSGD and HpaTHAS genes.

17.
PLoS One ; 19(5): e0304092, 2024.
Article in English | MEDLINE | ID: mdl-38787900

ABSTRACT

AIM: To analyze the relationship between burnout syndrome, cognitive functions, and sBDNF (Serum Brain-derived Neurotrophic Factor) in Mexican nurses. METHOD: A descriptive cross-sectional design was used. This study target staff nurses working in hospitals in Guanajuato, México. Demographic and working condition data were collected via questionnaire. The Maslach Burnout Inventory (MBI) was used to evaluate burnout. A blood sample were collected and processed by ELISA technique to measure sBDNF. Finally, the General Cognitive Assessment (CAB) of the Cognifit© neuropsychological battery was used to evaluated cognitive functions. RESULTS: Findings showed that there are sociodemographic characteristics and working conditions associated with burnout syndrome among nurses. Furthermore, the data demonstrated a significant decrease in sBDNF levels in burnout nurses and a negative correlation between BDNF levels and burnout syndrome. Additionally, these burnout nurse also revealed significant cognitive impairment in reasoning, memory, and attention as well as total scores of CAB. Interestingly, we found a positive correlation between sBDNF levels and the cognitive deficits in burnout nurse. CONCLUSION: Reduced BDNF levels could be a biological indicator or part of the pathological process of burnout, which could affect cognitive abilities. Reduced cognitive function in nurses has relevant implications and emphasizes the need for specialized preventive strategies because nurses make clinical decisions concerning their patients, whose situations are constantly changing.


Subject(s)
Brain-Derived Neurotrophic Factor , Burnout, Professional , Cognition , Humans , Brain-Derived Neurotrophic Factor/blood , Burnout, Professional/epidemiology , Burnout, Professional/psychology , Mexico/epidemiology , Female , Adult , Cognition/physiology , Male , Cross-Sectional Studies , Nursing Staff, Hospital/psychology , Nursing Staff, Hospital/statistics & numerical data , Middle Aged , Nurses/psychology , Surveys and Questionnaires , Young Adult
18.
Int Rev Psychiatry ; 25(3): 291-300, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23859092

ABSTRACT

The utilization of competencies in medical education is relatively recent. In 1999 the United States Accreditation Council for Graduate Medical Education (ACGME) established six main competencies. Since then, the American Board of Psychiatry and Neurology have approved a specific list of competencies for their specialities in each of the ACGME's core competency areas. Assessment of competencies in both medical students and residents can be achieved through such methods as structured case discussion, direct observation, simulation, standardized patients, and 360-degree assessments, etc. Each assessment methodology has specific applications in the discipline of psychiatry. This paper reviews the different methods for assessing competencies with specific examples in psychiatric education. It is not intended as a comprehensive review of all assessment methods, but to provide examples and strategies to guide psychiatric educators in their practice. Students and residents were intentionally separated because there are differences in the teaching goals and objectives, and thus in the assessment purposes and design. Students are general, undifferentiated physicians-in-training who need to learn about psychiatric nosology, examinations, and treatment. Residents are mental health professionals who need more in-depth supervision in order to hone skills in all the specialized areas that arise in psychiatric practices, making supervision a vital part of residency programs.


Subject(s)
Education, Medical/standards , Educational Measurement/standards , Professional Competence/standards , Psychiatry/education , Humans
19.
BMC Sports Sci Med Rehabil ; 15(1): 114, 2023 Sep 20.
Article in English | MEDLINE | ID: mdl-37730648

ABSTRACT

BACKGROUND: Lumbar spine injuries in fast bowlers account for the greatest missed playing time in cricket. A range of extrinsic and intrinsic variables are hypothesised to be associated with low back pain and lumbar spine injury in fast bowlers, and an improved understanding of intrinsic variables is necessary as these may alter load tolerance and injury risk associated with fast bowling. This review critically evaluated studies reporting intrinsic variables associated with low back pain and lumbar spine injury in fast bowlers and identified areas for future investigation. METHODS: OVID Medline, EMBASE, SPORTDiscus, CINAHL, Web of Science and SCOPUS databases were last searched on 3 June 2022 to identify studies investigating intrinsic variables associated with low back pain and lumbar spine injury in cricket fast bowlers. Terms relevant to cricket fast bowling, and intrinsic variables associated with lumbar spine injury and low back pain in fast bowlers were searched. 1,503 abstracts were screened, and 118 full-text articles were appraised to determine whether they met inclusion criteria. Two authors independently screened search results and assessed risk of bias using a modified version of the Quality in Prognostic Studies tool. RESULTS: Twenty-five studies met the inclusion criteria. Overall, no included studies demonstrated a low risk of bias, two studies were identified as moderate risk, and twenty-three studies were identified as high risk. Conflicting results were reported amongst studies investigating associations of fast bowling kinematics and kinetics, trunk and lumbar anatomical features, anthropometric traits, age, and neuromuscular characteristics with low back pain and lumbar spine injury. CONCLUSION: Inconsistencies in results may be related to differences in study design, injury definitions, participant characteristics, measurement parameters, and statistical analyses. Low back pain and lumbar spine injury occurrence in fast bowlers remain high, and this may be due to an absence of low bias studies that have informed recommendations for their prevention. Future research should employ clearly defined injury outcomes, analyse continuous datasets, utilise models that better represent lumbar kinematics and kinetics during fast bowling, and better quantify previous injury, lumbar anatomical features and lumbar maturation. TRIAL REGISTRATION: Open Science Framework https://doi.org/10.17605/OSF.IO/ERKZ2 .

20.
J Clin Exp Dent ; 15(8): e641-e648, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37674602

ABSTRACT

Background: To evaluate the in vitro degree of marginal microleakage in indirect Class II onlay restorations cemented with dual self-adhesive, universal adhesive and dual adhesive. Material and Methods: In the present in vitro experimental study, a total of 54 human premolar teeth were prepared and divided into three equal groups (n = 18) for placement of onlay-type restorations cemented with A: Allcem™ dual-cure adhesive cement), B: RelyX™U200 dual-cure self-adhesive cement and C: RelyX™ Ultimate universal adhesive cement. All restorations were subjected to 10,000 thermocycles between 5°C and 55°C and immersed in a 1M silver nitrate solution for 6 hours. The crowns were then sectioned mesiodistally and observed under a stereo microscope to determine the degree of marginal microleakage in the cervical area. Results: The onlay restorations cemented with RelyX Ultimate did not present microleakage in the majority of cases (77.8%). Restorations cemented with RelyX U200 showed predominantly microleakage up to the pulp floor in 83.3% of the total, being this significantly higher microleakage than in restorations cemented with RelyX Ultimate and Allcem Dual (p<0.001 and p<0.001 respectively). There was no significant difference in microleakage between the last two mentioned cements (p=0.255). Conclusions: Allcem dual adhesive cement and RelyX Ultimate universal adhesive showed significantly less microleakage than RelyX U200 dual-curing self-adhesive cement at the cervical level, with predominantly no microleakage and microleakage down to the enamel, respectively. The use of RelyX Ultimate cement in indirect restorations is recommended as it showed better marginal adaptation. Key words:Microleakage, human teeth, adhesion, adhesive cement, thermal cycling, onlay restoration.

SELECTION OF CITATIONS
SEARCH DETAIL