Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 50
Filtrar
1.
Eur J Pharm Biopharm ; 200: 114339, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38789061

RESUMO

Peptides, despite their therapeutic potential, face challenges with undesirable pharmacokinetic (PK) properties and biodistribution, including poor oral absorption and cellular uptake, and short plasma elimination half-lives. Lipidation of peptides is a common strategy to improve their physicochemical and PK properties, making them viable drug candidates. For example, the plasma half-life of peptides has been extended via conjugation to lipids that are proposed to promote binding to serum albumin and thus protect against rapid clearance. Recent work has shown that lipid conjugation to oligodeoxynucleotides, polymers and small molecule drugs results in association not only with albumin, but also with lipoproteins, resulting in half-life prolongation and transport from administration sites via the lymphatics. Enhancing delivery into the lymph increases the efficacy of vaccines and therapeutics with lymphatic targets such as immunotherapies. In this study, the plasma PK, lymphatic uptake, and bioavailability of the glucagon-like peptide-1 (GLP-1) receptor agonist peptides, liraglutide (lipidated) and exenatide (non-lipidated), were investigated following subcutaneous (SC) administration to rats. As expected, liraglutide displayed an apparent prolonged plasma half-life (9.1 versus 1 h), delayed peak plasma concentrations and lower bioavailability (∼10 % versus ∼100 %) compared to exenatide after SC administration. The lymphatic uptake of both peptides was relatively low (<0.5 % of the dose) although lymph to plasma concentration ratios were greater than one for several early timepoints suggesting some direct uptake into lymph. The low lymphatic uptake may be due to the nature of the conjugated lipid (a single-chain C16 palmitic acid in liraglutide) but suggests that other peptides with similar lipid conjugations may also have relatively modest lymphatic uptake. If delivery to the lymph is desired, conjugation to more lipophilic moieties with higher albumin and/or lipoprotein binding efficiencies, such as diacylglycerols, may be appropriate.


Assuntos
Exenatida , Liraglutida , Peptídeos , Ratos Sprague-Dawley , Animais , Exenatida/farmacocinética , Exenatida/administração & dosagem , Exenatida/farmacologia , Liraglutida/farmacologia , Liraglutida/farmacocinética , Liraglutida/administração & dosagem , Ratos , Masculino , Peptídeos/farmacocinética , Peptídeos/administração & dosagem , Lipídeos/química , Meia-Vida , Peçonhas/farmacocinética , Peçonhas/administração & dosagem , Disponibilidade Biológica , Distribuição Tecidual , Injeções Subcutâneas , Linfa/metabolismo , Linfa/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Peptídeo 1 Semelhante ao Glucagon/farmacocinética , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Sistema Linfático/metabolismo , Sistema Linfático/efeitos dos fármacos , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacologia
2.
Schizophr Res ; 267: 451-461, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38643726

RESUMO

The methylazoxymethanol acetate (MAM) rodent model is used to study aspects of schizophrenia. However, numerous studies that have employed this model have used only males, resulting in a dearth of knowledge on sex differences in brain function and behaviour. The purpose of this study was to determine whether differences exist between male and female MAM rats in neuronal oscillatory function within and between the prefrontal cortex (PFC), ventral hippocampus (vHIP) and thalamus, behaviour, and in proteins linked to schizophrenia neuropathology. We showed that female MAM animals exhibited region-specific alterations in theta power, elevated low and high gamma power in all regions, and elevated PFC-thalamus high gamma coherence. Male MAM rats had elevated beta and low gamma power in PFC, and elevated vHIP-thalamus coherence. MAM females displayed impaired reversal learning whereas MAM males showed impairments in spatial memory. Glycogen synthase kinase-3 (GSK-3) was altered in the thalamus, with female MAM rats displaying elevated GSK-3α phosphorylation. Male MAM rats showed higher expression and phosphorylation GSK-3α, and higher expression of GSK-ß. Sex-specific changes in phosphorylated Tau levels were observed in a region-specific manner. These findings demonstrate there are notable sex differences in behaviour, oscillatory network function, and GSK-3 signaling in MAM rats, thus highlighting the importance of inclusion of both sexes when using this model to study schizophrenia.


Assuntos
Modelos Animais de Doenças , Acetato de Metilazoximetanol , Esquizofrenia , Caracteres Sexuais , Animais , Acetato de Metilazoximetanol/farmacologia , Esquizofrenia/fisiopatologia , Esquizofrenia/induzido quimicamente , Esquizofrenia/metabolismo , Feminino , Masculino , Ratos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/fisiopatologia , Córtex Pré-Frontal/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Tálamo/efeitos dos fármacos , Tálamo/fisiopatologia , Tálamo/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas tau/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Neurônios/patologia , Ratos Sprague-Dawley
3.
Arch Razi Inst ; 78(3): 955-961, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-38028828

RESUMO

Reference intervals aid clinical decision-making for clinical chemistry values. Laboratory test results are compared to reference intervals to aid in the diagnosis, therapy, and monitoring decisions. Due to the differences in ethnicity, gender, age, and analytical methods, reference intervals (RIs) vary between populations. This study aimed to establish the reference values for renal function tests in targeted populations in Indonesia. This research was conducted with a cross-sectional observational analytic design. The research sample consisted of medical check-up data from health professionals at Dr. Mohammad Hoesin Hospital in Palembang, Indonesia. The Kolmogorov-Smirnov test was used to determine the normality of data distribution.   The RIs were computed using reference limits at the 2.5th and 97.5th percentiles (abnormal distribution) or ±two standard deviations (±2 SD) (normal distribution).  The independent t-test (parametric) or Mann-Whitney test was used to compare the RIs of males and females (non-parametric). Males and females had a significant difference (P<0.001) regarding the values of uric acid, urea, and creatinine parameters, requiring the reference intervals to be separated. The following reference intervals were established: uric acid: 230,78-526,99 mol/L for males and 179,03-415.17 mol/L for females, urea: 2,22-4,99 mmol/L for males and 1,78-4,28 mmol/L for females, and creatinine: 61,01-106,99 mol/L for males and 40,67-77,81 mol/L for females. This study defined gender-specific RIs for three renal function test parameters for the adult population of Palembang, Indonesia. The deployment of population-specific RIs may facilitate better laboratory testing.


Assuntos
Química Clínica , Ácido Úrico , Masculino , Feminino , Humanos , Indonésia , Centros de Atenção Terciária , Creatinina , Estudos Transversais , Valores de Referência , Ureia , Rim/fisiologia
4.
Sens Actuators B Chem ; 3902023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37384350

RESUMO

Oligonucleotide-functionalized graphene biosensors show immense promise for use as label-free point of care devices for detection of nucleic acid biomarkers at clinically relevant levels. Graphene-based nucleic acid sensors can be fabricated at low cost and have been shown to reach limits of detection in the attomolar range. Here we demonstrate devices functionalized with 22mer or 8omer DNA probes are capable of detecting full length genomic HIV-1 subtype B RNA, with a limit of detection below 1 aM in nuclease free water. We also show that these sensors are suitable for detection directly in Qiazol lysis reagent, again with a limit of detection below 1 aM for both 22mer and 8omer probes.

5.
J Womens Health (Larchmt) ; 32(4): 486-493, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36857710

RESUMO

Background: There has been an increase of women living in the United States who have experienced female genital cutting (FGC). However, limited research exists evaluating the experiences of obstetrician/gynecologists delivering care to this patient population. This study aimed to assess the overall experiences, including barriers and facilitators, of U.S.-based obstetrician/gynecologists (OBGYNs) with delivering care to patients with female genital cutting at a single academic health center in the United States. Materials and Methods: This is a qualitative study of OBGYNs at a large, U.S., urban, academic health center. OBGYNs participated in a one-on-one semistructured interview. Thematic analysis using a grounded theory approach was conducted to identify predominating themes regarding the overall experiences, barriers, and facilitators to delivering care to patients with FGC. Results: Analysis of 15 study interviews revealed 4 main themes impacting the ability of OBGYNs to deliver care to patients with FGC: (1) limited educational training on FGC, (2) challenges with identifying that a patient had FGC and with using the World Health Organization classification system, (3) questions regarding "normative" anatomy and reinfibulation after vaginal procedures, and (4) navigating affective responses of patient and self when FGC is encountered. Conclusion: The above findings have practical implications, showing that the limited educational experience and lack of a clear policy on how to manage the care of women with FGC lead to variation and even limitations in how care is delivered to these women. We encourage OBGYN professional societies to consider creating education and policy to aid clinicians in caring for patients with FGC.


Assuntos
Circuncisão Feminina , Medicina , Feminino , Humanos , Circuncisão Feminina/psicologia , Ginecologista , Pessoal de Saúde , Obstetra , Estados Unidos , Competência Cultural , Emigrantes e Imigrantes , Pesquisa Qualitativa
6.
Childs Nerv Syst ; 39(4): 1051-1058, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36662275

RESUMO

INTRODUCTION: The primary objective of neurosurgical management of malignant gliomas is maximal safe resection of the tumour. One of the main obstacles in achieving this is the ability to accurately discriminate between tumour edges and the surrounding healthy brain tissue. The use of fluorescence-guided surgery utilising 5-aminolevulinic acid (5-ALA), first introduced more than 20 years ago, has become an invaluable adjunct in high-grade glioma surgery in adults. However, as 5-ALA is not licensed for use in paediatric patients, the safety profile for such use remains undetermined. CASE REPORT: We describe the case of a 4-year-old boy who underwent 5-ALA-guided resection of a fourth ventricle anaplastic ependymoma. Although complete resection was achieved and the patient awoke from surgery well with no neurological deficits, the patient developed acute transaminitis, anaemia, thrombocytopaenia and coagulopathy postoperatively. The patient had a sudden neurological deterioration on postoperative day 2; imaging revealed that he had suffered a spontaneous right frontal intracerebral haemorrhage. The patient returned to theatre for surgical decompression and evacuation of the haematoma, and ultimately went on to make a full recovery. CONCLUSION: The use of 5-ALA in paediatric patients can be helpful in maximising surgical resection, but the associated safety profile remains undefined. Further research is urgently warranted in order to characterise the efficacy and risk of the use of 5-ALA in the paediatric population.


Assuntos
Neoplasias Encefálicas , Glioma , Cirurgia Assistida por Computador , Trombocitopenia , Masculino , Adulto , Humanos , Criança , Pré-Escolar , Ácido Aminolevulínico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Glioma/patologia , Cirurgia Assistida por Computador/métodos , Procedimentos Neurocirúrgicos/métodos , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/cirurgia
7.
MMWR Morb Mortal Wkly Rep ; 71(36): 1141-1147, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36074735

RESUMO

High prevalences of HIV and other sexually transmitted infections (STIs) have been reported in the current global monkeypox outbreak, which has affected primarily gay, bisexual, and other men who have sex with men (MSM) (1-5). In previous monkeypox outbreaks in Nigeria, concurrent HIV infection was associated with poor monkeypox clinical outcomes (6,7). Monkeypox, HIV, and STI surveillance data from eight U.S. jurisdictions* were matched and analyzed to examine HIV and STI diagnoses among persons with monkeypox and assess differences in monkeypox clinical features according to HIV infection status. Among 1,969 persons with monkeypox during May 17-July 22, 2022, HIV prevalence was 38%, and 41% had received a diagnosis of one or more other reportable STIs in the preceding year. Among persons with monkeypox and diagnosed HIV infection, 94% had received HIV care in the preceding year, and 82% had an HIV viral load of <200 copies/mL, indicating HIV viral suppression. Compared with persons without HIV infection, a higher proportion of persons with HIV infection were hospitalized (8% versus 3%). Persons with HIV infection or STIs are disproportionately represented among persons with monkeypox. It is important that public health officials leverage systems for delivering HIV and STI care and prevention to reduce monkeypox incidence in this population. Consideration should be given to prioritizing persons with HIV infection and STIs for vaccination against monkeypox. HIV and STI screening and other recommended preventive care should be routinely offered to persons evaluated for monkeypox, with linkage to HIV care or HIV preexposure prophylaxis (PrEP) as appropriate.


Assuntos
Infecções por HIV , Mpox , Profilaxia Pré-Exposição , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Animais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Humanos , Masculino , Mpox/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções Sexualmente Transmissíveis/prevenção & controle
8.
J Vis Exp ; (185)2022 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-35938840

RESUMO

Magnetic force microscopy (MFM) enables mapping local magnetic fields across a sample surface with nanoscale resolution. To perform MFM, an atomic force microscopy (AFM) probe whose tip has been magnetized vertically (i.e., perpendicular to the probe cantilever) is oscillated at a fixed height above the sample surface. The resultant shifts in the oscillation phase or frequency, which are proportional to the magnitude and sign of the vertical magnetic force gradient at each pixel location, are then tracked and mapped. Although the spatial resolution and sensitivity of the technique increases with decreasing lift height above the surface, this seemingly straightforward path to improved MFM images is complicated by considerations such as minimizing topographical artifacts due to shorter range van der Waals forces, increasing the oscillation amplitude to further improve sensitivity, and the presence of surface contaminants (in particular water due to humidity under ambient conditions). In addition, due to the orientation of the probe's magnetic dipole moment, MFM is intrinsically more sensitive to samples with an out-of-plane magnetization vector. Here, high-resolution topographical and magnetic phase images of single and bicomponent nanomagnet artificial spin-ice (ASI) arrays obtained in an inert (argon) atmosphere glovebox with <0.1 ppm O2 and H2O are reported. Optimization of lift height and drive amplitude for high resolution and sensitivity while simultaneously avoiding the introduction of topographical artifacts is discussed, and detection of the stray magnetic fields emanating from either end of the nanoscale bar magnets (~250 nm long and <100 nm wide) aligned in the plane of the ASI sample surface is shown. Likewise, using the example of a Ni-Mn-Ga magnetic shape memory alloy (MSMA), MFM is demonstrated in an inert atmosphere with magnetic phase sensitivity capable of resolving a series of adjacent magnetic domains each ~200 nm wide.

9.
J Vis Exp ; (184)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35815966

RESUMO

Kelvin probe force microscopy (KPFM), sometimes referred to as surface potential microscopy, is the nanoscale version of the venerable scanning Kelvin probe, both of which measure the Volta potential difference (VPD) between an oscillating probe tip and a sample surface by applying a nulling voltage equal in magnitude but opposite in sign to the tip-sample potential difference. By scanning a conductive KPFM probe over a sample surface, nanoscale variations in surface topography and potential can be mapped, identifying likely anodic and cathodic regions, as well as quantifying the inherent material driving force for galvanic corrosion. Subsequent co-localization of KPFM Volta potential maps with advanced scanning electron microscopy (SEM) techniques, including back scattered electron (BSE) images, energy dispersive spectroscopy (EDS) elemental composition maps, and electron backscattered diffraction (EBSD) inverse pole figures can provide further insight into structure-property-performance relationships. Here, the results of several studies co-localizing KPFM with SEM on a wide variety of alloys of technological interest are presented, demonstrating the utility of combining these techniques at the nanoscale to elucidate corrosion initiation and propagation. Important points to consider and potential pitfalls to avoid in such investigations are also highlighted: in particular, probe calibration and the potential confounding effects on the measured VPDs of the testing environment and sample surface, including ambient humidity (i.e., adsorbed water), surface reactions/oxidation, and polishing debris or other contaminants. Additionally, an example is provided of co-localizing a third technique, scanning confocal Raman microscopy, to demonstrate the general applicability and utility of the co-localization method to provide further structural insight beyond that afforded by electron microscopy-based techniques.

11.
Nat Mater ; 21(7): 795-803, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35501365

RESUMO

Intercalation-type metal oxides are promising negative electrode materials for safe rechargeable lithium-ion batteries due to the reduced risk of Li plating at low voltages. Nevertheless, their lower energy and power density along with cycling instability remain bottlenecks for their implementation, especially for fast-charging applications. Here, we report a nanostructured rock-salt Nb2O5 electrode formed through an amorphous-to-crystalline transformation during repeated electrochemical cycling with Li+. This electrode can reversibly cycle three lithiums per Nb2O5, corresponding to a capacity of 269 mAh g-1 at 20 mA g-1, and retains a capacity of 191 mAh g-1 at a high rate of 1 A g-1. It exhibits superb cycling stability with a capacity of 225 mAh g-1 at 200 mA g-1 for 400 cycles, and a Coulombic efficiency of 99.93%. We attribute the enhanced performance to the cubic rock-salt framework, which promotes low-energy migration paths. Our work suggests that inducing crystallization of amorphous nanomaterials through electrochemical cycling is a promising avenue for creating unconventional high-performance metal oxide electrode materials.

12.
Urology ; 163: 196-201, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35469809

RESUMO

OBJECTIVE: To evaluate the association between ethnicity/insurance status and time to kidney stone surgery. METHODS: We retrospectively assessed all patients with evaluation of nephrolithiasis in the emergency room (ED), followed by definitive stone surgery (ureteroscopy/percutaneous nephrolithotomy/ESWL) at our major academic health system consisting of 3 hospitals in a dense, urban center. RESULTS: A total of 682 patients were included. A total of 2.8% (n = 19) were uninsured, 19.3% (n = 132) were enrolled in Medicaid, 23.3% (n = 159) were enrolled in Medicare and 54.5% (n = 372) had commercial insurance. Uninsured patients had a short median time to surgery of only 21 days (IQR 6-49), while Medicare patients had a longer time at 39 days, (IQR 17-64), although these were not significantly different (P =.12). Black race was associated with a higher percentage of uninsured and Medicaid patients (P ≤.001). There was no difference in clinical or patient reported characteristics between the insurance groups (all P >.05) 6.9%, 17.7%, 26.7%, and 48.6% of patients self-identified as Hispanic, Other, Black, and White, respectively. Hispanic patients had the shortest median time to surgery of 28 days (IQR 10-48), while Black patients the longest with a median of 38.5 days (18-72) (P =.007). Clinical variables at presentation including nausea/vomiting, hydronephrosis and sepsis were not statistically significant between the patient groups (all P >.05). CONCLUSION: Our study illustrates persistent delays in surgery scheduling for Black patients regardless of insurance status. This should inform practice patterns for urology providers, highlighting our need to enact institutional safety nets to promote expedient follow up for a vulnerable population.


Assuntos
Etnicidade , Cálculos Renais , Idoso , Humanos , Cobertura do Seguro , Cálculos Renais/cirurgia , Medicaid , Pessoas sem Cobertura de Seguro de Saúde , Medicare , Estudos Retrospectivos , Estados Unidos
13.
eNeuro ; 9(3)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35470227

RESUMO

Hippocampal seizures are a defining feature of mesial temporal lobe epilepsy (MTLE). Area CA1 of the hippocampus is commonly implicated in the generation of seizures, which may occur because of the activity of endogenous cell populations or of inputs from other regions within the hippocampal formation. Simultaneously observing activity at the cellular and network scales in vivo remains challenging. Here, we present a novel technology for simultaneous electrophysiology and multicellular calcium imaging of CA1 pyramidal cells (PCs) in mice enabled by a transparent graphene-based microelectrode array (Gr MEA). We examine PC firing at seizure onset, oscillatory coupling, and the dynamics of the seizure traveling wave as seizures evolve. Finally, we couple features derived from both modalities to predict the speed of the traveling wave using bootstrap aggregated regression trees. Analysis of the most important features in the regression trees suggests a transition among states in the evolution of hippocampal seizures.


Assuntos
Epilepsia do Lobo Temporal , Grafite , Animais , Hipocampo , Camundongos , Microeletrodos , Convulsões
14.
Female Pelvic Med Reconstr Surg ; 28(6): e154-e156, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35234182

RESUMO

IMPORTANCE: A sequelae of the removal of pelvic organ prolapse (POP) transvaginal mesh products from the U.S. market is that current and future women's health providers may be unfamiliar with mesh products historically used to treat pelvic floor disorders. OBJECTIVES: Our goal was to create an easily accessible resource to address this knowledge gap. STUDY DESIGN: An online database of mesh products used to treat POP and urinary incontinence was created with information, photographs, and videos collated from internet searches; manufacturer materials; and other primary sources. The database was then linked to a free smartphone application. RESULTS: This smartphone application includes, to the best of our knowledge, all mesh products used in the United States for the treatment of POP and stress urinary incontinence through December 2020. Included in the application are product descriptions of mesh color, size, design, and attachment points. Photographs and videos, when available, are included. The application is organized by mesh product name, but it is also searchable by other categories, such as manufacturer name and color.To download the application to a smart phone, go to vaginalmeshcatalogue.glideapp.io/ on a web browser or access via the QR code. Once the website is loaded, you can interact with the mesh catalog as a website or save it to the phone's home screen as an application. CONCLUSIONS: Health care providers of all experience levels can use this free application for educational and clinical purposes to better understand patients' histories, improve preoperative planning, and enhance patient counseling.


Assuntos
Prolapso de Órgão Pélvico , Slings Suburetrais , Telas Cirúrgicas , Incontinência Urinária por Estresse , Bases de Dados Factuais , Feminino , Humanos , Prolapso de Órgão Pélvico/cirurgia , Slings Suburetrais/classificação , Telas Cirúrgicas/classificação , Estados Unidos , Incontinência Urinária por Estresse/cirurgia
15.
MMWR Morb Mortal Wkly Rep ; 71(2): 66-68, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35025854

RESUMO

During October 2019, the West Virginia Bureau for Public Health (WVBPH) noted that an increasing number of persons who inject drugs (PWID) in Kanawha County received a diagnosis of HIV. The number of HIV diagnoses among PWID increased from less than five annually during 2016-2018 to 11 during January-October 2019 (Figure). Kanawha County (with an approximate population of 180,000*) has high rates of opioid use disorder and overdose deaths, which have been increasing since 2016,† and the county is located near Cabell County, which experienced an HIV outbreak among PWID during 2018-2019 (1,2). In response to the increase in HIV diagnoses among PWID in 2019, WVBPH released a Health Advisory§; and WVBPH and Kanawha-Charleston Health Department (KCHD) convened an HIV task force, conducted care coordination meetings, received CDC remote assistance to support response activities, and expanded HIV testing and outreach.


Assuntos
Surtos de Doenças , Usuários de Drogas , Infecções por HIV/epidemiologia , Adulto , Feminino , Humanos , Masculino , Abuso de Substâncias por Via Intravenosa/epidemiologia , West Virginia/epidemiologia
16.
Cell Mol Neurobiol ; 42(5): 1341-1353, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33392916

RESUMO

Alterations in glycogen synthase kinase-3ß (GSK-3ß) activity have been implicated in disorders of cognitive impairment, including Alzheimer's disease and schizophrenia. Cognitive dysfunction is also characterized by the dysregulation of neuronal oscillatory activity, macroscopic electrical rhythms in brain that are critical to systems communication. A direct functional relationship between GSK-3ß and neuronal oscillations has not been elucidated. Therefore, in the present study, using an adeno-associated viral vector containing a persistently active mutant form of GSK-3ß, GSK-3ß(S9A), the impact of elevated kinase activity in prefrontal cortex (PFC) or ventral hippocampus (vHIP) of rats on neuronal oscillatory activity was evaluated. GSK-3ß(S9A)-induced changes in learning and memory were also assessed and the phosphorylation status of tau protein, a substrate of GSK-3ß, examined. It was demonstrated that increasing GSK-3ß(S9A) activity in either the PFC or vHIP had similar effects on neuronal oscillatory activity, enhancing theta and/or gamma spectral power in one or both regions. Increasing PFC GSK-3ß(S9A) activity additionally suppressed high gamma PFC-vHIP coherence. These changes were accompanied by deficits in recognition memory, spatial learning, and/or reversal learning. Elevated pathogenic tau phosphorylation was also evident in regions where GSK-3ß(S9A) activity was upregulated. The neurophysiological and learning and memory deficits induced by GSK-3ß(S9A) suggest that aberrant GSK-3ß signalling may not only play an early role in cognitive decline in Alzheimer's disease but may also have a more central involvement in disorders of cognitive dysfunction through the regulation of neurophysiological network function.


Assuntos
Doença de Alzheimer , Glicogênio Sintase Quinase 3 beta/metabolismo , Doença de Alzheimer/metabolismo , Animais , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Neurônios/metabolismo , Fosforilação , Ratos , Proteínas tau/metabolismo
17.
Soc Sci Med ; 300: 114453, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34663541

RESUMO

A number of conceptual frameworks have emerged with the goal of helping clinicians understand and navigate the intersections of the health system and broader political, economic, and cultural processes when they care for patients. In this study, we analyze the impact that one emerging framework, "structural competency," had on medical students' and physicians' understanding of societal problems affecting patient health and the practices of health systems. In this sub-analysis of a longitudinal qualitative study conducted between August and December 2020, we analyzed 19 semi-structured interviews with 7 first-year medical students, 7 upper-level medical students, and 5 physician course facilitators who participated in a course called Introduction to Medicine and Society at an medical school in the United States affiliated with a large urban academic medical center. This paper focuses on three main findings: how medical students and faculty describe "structures" and their effects on patients and patient care; how they use or imagine using structural competency to improve patient-physician communication and work interprofessionally to address social needs; and the emotional and personal reactions that confronting societal challenges provokes. We conclude that structural competency enhances existing efforts to improve patient-physician communication and to address patients' social needs. However, we highlight how structural competency efforts might fall short of their goal to shift physicians' perspectives "upstream" to the determinants of health due to both critical ambiguities in the concept and inattention to the emotional and personal impacts of addressing societal problems in the clinic. These findings have practical implications for how clinicians are trained to act on societal issues from within the health system and conceptual implications for refining how existing frameworks and curricula conceive of the intersection between healthcare and broader processes.


Assuntos
Educação Médica , Estudantes de Medicina , Currículo , Humanos , Pesquisa Qualitativa , Faculdades de Medicina , Estados Unidos
18.
Transl Psychiatry ; 11(1): 625, 2021 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34887388

RESUMO

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder that is associated with functional brain alterations that underlie the expression of behaviour. Males are diagnosed up to four times more than females, and sex differences have been identified in memory, cognitive flexibility, verbal fluency, and social communication. Unfortunately, there exists a lack of information on the sex-dependent mechanisms of ASD, as well as biological markers to distinguish sex-specific symptoms in ASD. This can often result in a standardized diagnosis for individuals across the spectrum, despite significant differences in the various ASD subtypes. Alterations in neuronal connectivity and oscillatory activity, such as is observed in ASD, are highly coupled to behavioural states. Yet, despite the well-identified sexual dimorphisms that exist in ASD, these functional patterns have rarely been analyzed in the context of sex differences or symptomology. This review summarizes alterations in neuronal oscillatory function in ASD, discusses the age, region, symptom and sex-specific differences that are currently observed across the spectrum, and potential targets for regulating neuronal oscillatory activity in ASD. The need to identify sex-specific biomarkers, in order to facilitate specific diagnostic criteria and allow for more targeted therapeutic approaches for ASD will also be discussed.


Assuntos
Transtorno do Espectro Autista , Caracteres Sexuais , Transtorno do Espectro Autista/diagnóstico , Encéfalo , Feminino , Humanos , Masculino
19.
Brain Sci ; 11(9)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34573220

RESUMO

Dopamine is an important neurotransmitter that plays a key role in neuropsychiatric illness. Sex differences in dopaminergic signaling have been acknowledged for decades and have been linked to sex-specific heterogeneity in both dopamine-related behaviours as well as in various neuropsychiatric disorders. However, the overall number of studies that have evaluated sex differences in dopamine signaling, both in health and in these disorders, is low. This review will bring together what is known regarding sex differences in innate dopamine receptor expression and function, as well as highlight the known sex-specific roles of dopamine in addiction, depression, anxiety, schizophrenia, and attention deficit hyperactivity disorder. Due to differences in prognosis, diagnosis, and symptomatology between male and female subjects in disorders that involve dopamine signaling, or in responses that utilize pharmacological interventions that target dopamine receptors, understanding the fundamental sex differences in dopamine receptors is of vital importance for the personalization of therapeutic treatment strategies.

20.
PLoS One ; 16(8): e0256692, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34437619

RESUMO

Parent-child conversations are important for children's cognitive development, children's ability to cope with stressful events, and can shape children's beliefs about the causes of illness. In the context of a global pandemic, families have faced a multitude of challenges, including changes to their routines, that they need to convey to their children. Thus, parent-child conversations about the coronavirus pandemic might convey information about the causes of illness, but also about how and why it is necessary for children to modify their behaviors to comply with new social norms and medical guidance. The main goal of this study was to examine the questions children ask about the COVID-19 pandemic and how parents answer them. This survey included responses from a national sample of 349 predominantly white parents of children between the ages of 3 and 12 recruited through Amazon's Mechanical Turk in United States. Parents reported that although children asked about COVID-19 and its causes (17.3%), children asked primarily about lifestyle changes that occurred as a result of the pandemic (24.0%) and safety (18.4%). Parents reported answering these questions by emphasizing that the purpose of different preventative measures was to protect the child (11.8%) or the family (42.7%) and providing reassurance (13.3%). Many parents discussed how it was their social responsibility to slow the spread of the virus (38.4%). Parents of younger children tended to shield them from information about COVID-19 (p = .038), while parents with more knowledge were more likely to provide explanations (p < .001). Our analysis shows that families not only discuss information about the virus but also information about changes to their lifestyle, preventative measures, and social norms.


Assuntos
COVID-19/epidemiologia , Pais/psicologia , Adaptação Psicológica , Adulto , Ansiedade/patologia , COVID-19/virologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Relações Pais-Filho , SARS-CoV-2/isolamento & purificação , Inquéritos e Questionários , Estados Unidos/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...