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1.
PLoS One ; 16(10): e0258095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34610034

RESUMO

INTRODUCTION: Several studies have described typical clinical manifestations, including fever, cough, diarrhea, and fatigue with COVID-19 infection. However, there are limited data on the association between the presence of neurological manifestations on hospital admission, disease severity, and outcomes. We sought to investigate this correlation to help understand the disease burden. METHODS: We delivered a multi-center retrospective study of positive laboratory-confirmed COVID-19 patients. Clinical presentation, laboratory values, complications, and outcomes data were reported. Our findings of interest were Intensive Care Unit (ICU) admission, intubation, mechanical ventilation, and in-hospital mortality. RESULTS: A total of 502 patients with a mean age of 60.83 ± 15.5 years, of them 71 patients (14.14%) presented with altered mental status, these patients showed higher odds of ICU admission (OR = 2.06, 95%CI = 1.18 to 3.59, p = 0.01), mechanical ventilation (OR = 3.28, 95%CI = 1.86 to 5.78, p < 0.001), prolonged (>4 days) mechanical ventilation (OR = 4.35, 95%CI = 1.89 to 10, p = 0.001), acute kidney injury (OR = 2.18, 95%CI = 1.28 to 3.74, p = 0.004), and mortality (HR = 2.82, 95%CI = 1.49 to 5.29, p = 0.01). CONCLUSION: This cohort study found that neurological presentations are associated with higher odds of adverse events. When examining patients with neurological manifestations, clinicians should suspect COVID-19 to avoid delayed diagnosis or misdiagnosis and lose the chance to treat and prevent further transmission.


Assuntos
COVID-19/psicologia , Transtornos Mentais/patologia , Injúria Renal Aguda/etiologia , Adulto , Idoso , COVID-19/mortalidade , COVID-19/patologia , COVID-19/virologia , Estudos de Coortes , Feminino , Mortalidade Hospitalar , Hospitalização , Humanos , Unidades de Terapia Intensiva , Tempo de Internação , Masculino , Transtornos Mentais/etiologia , Pessoa de Meia-Idade , Razão de Chances , Modelos de Riscos Proporcionais , Respiração Artificial , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação
2.
Int J Mol Sci ; 22(17)2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34502412

RESUMO

Maternal inflammation during pregnancy causes later-in-life alterations of the offspring's brain structure and function. These abnormalities increase the risk of developing several psychiatric and neurological disorders, including schizophrenia, intellectual disability, bipolar disorder, autism spectrum disorder, microcephaly, and cerebral palsy. Here, we discuss how astrocytes might contribute to postnatal brain dysfunction following maternal inflammation, focusing on the signaling mediated by two families of plasma membrane channels: hemi-channels and pannexons. [Ca2+]i imbalance linked to the opening of astrocytic hemichannels and pannexons could disturb essential functions that sustain astrocytic survival and astrocyte-to-neuron support, including energy and redox homeostasis, uptake of K+ and glutamate, and the delivery of neurotrophic factors and energy-rich metabolites. Both phenomena could make neurons more susceptible to the harmful effect of prenatal inflammation and the experience of a second immune challenge during adulthood. On the other hand, maternal inflammation could cause excitotoxicity by producing the release of high amounts of gliotransmitters via astrocytic hemichannels/pannexons, eliciting further neuronal damage. Understanding how hemichannels and pannexons participate in maternal inflammation-induced brain abnormalities could be critical for developing pharmacological therapies against neurological disorders observed in the offspring.


Assuntos
Astrócitos/metabolismo , Canais Iônicos/metabolismo , Transtornos Mentais , Complicações na Gravidez , Efeitos Tardios da Exposição Pré-Natal , Astrócitos/patologia , Transporte Biológico Ativo , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Transtornos Mentais/etiologia , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Transtornos do Neurodesenvolvimento/etiologia , Transtornos do Neurodesenvolvimento/metabolismo , Transtornos do Neurodesenvolvimento/patologia , Gravidez , Complicações na Gravidez/metabolismo , Complicações na Gravidez/patologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/patologia
3.
Am J Hum Genet ; 108(10): 1866-1879, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34582792

RESUMO

Complex traits and diseases can be influenced by both genetics and environment. However, given the large number of environmental stimuli and power challenges for gene-by-environment testing, it remains a critical challenge to identify and prioritize specific disease-relevant environmental exposures. We propose a framework for leveraging signals from transcriptional responses to environmental perturbations to identify disease-relevant perturbations that can modulate genetic risk for complex traits and inform the functions of genetic variants associated with complex traits. We perturbed human skeletal-muscle-, fat-, and liver-relevant cell lines with 21 perturbations affecting insulin resistance, glucose homeostasis, and metabolic regulation in humans and identified thousands of environmentally responsive genes. By combining these data with GWASs from 31 distinct polygenic traits, we show that the heritability of multiple traits is enriched in regions surrounding genes responsive to specific perturbations and, further, that environmentally responsive genes are enriched for associations with specific diseases and phenotypes from the GWAS Catalog. Overall, we demonstrate the advantages of large-scale characterization of transcriptional changes in diversely stimulated and pathologically relevant cells to identify disease-relevant perturbations.


Assuntos
Interação Gene-Ambiente , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Doenças Autoimunes/etiologia , Doenças Autoimunes/patologia , Humanos , Transtornos Mentais/etiologia , Transtornos Mentais/patologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/patologia , Fenótipo
4.
Int J Mol Sci ; 22(17)2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34502322

RESUMO

Vasopressin is a ubiquitous molecule playing an important role in a wide range of physiological processes thereby implicated in the pathomechanism of many disorders. Its effect is well characterized through V2 receptors, which regulates the water resorption in kidney, while its vasoconstrictory effect through V1a receptor also received a lot of attention in the maintenance of blood pressure during shock. However, the most striking is its central effect both through the V1b receptors in stress-axis regulation as well as through V1a receptors regulating many aspects of our behavior (e.g., social behavior, learning and memory). Vasopressin has been implicated in the development of depression, due to its connection with chronic stress, as well as schizophrenia because of its involvement in social interactions and memory processes. Epigenetic changes may also play a role in the development of these disorders. The possible mechanism includes DNA methylation, histone modification and/or micro RNAs, and these possible regulations will be in the focus of our present review.


Assuntos
Epigênese Genética , Homeostase , Transtornos Mentais/patologia , Receptores de Vasopressinas/metabolismo , Vasopressinas/metabolismo , Animais , Humanos , Transtornos Mentais/genética , Transtornos Mentais/metabolismo , Receptores de Vasopressinas/genética , Transdução de Sinais , Vasopressinas/genética
5.
Sci Rep ; 11(1): 17616, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475458

RESUMO

Morphological changes in the child skull due to mechanical and metabolic stimulation and synostosis of the suture are well known. On the other hand, few studies have focused on clinical conditions relevant for adult skull deformity. We retrospectively reviewed computed tomography (CT) findings obtained from 365 cases that were treated for head injuries, moyamoya disease, cervical internal carotid artery stenosis, and mental diseases, and investigated the morphological changes in the skull associated with these diseases. The findings from head injuries were used not only for control subjects, but also for the analysis of generational changes in skull shape based on birth year. Head shape had a brachiocephalic tendency with occipital flattening in people born from the 1950s onwards. Cases of moyamoya disease, cervical internal carotid artery stenosis, and mental diseases showed significantly thicker frontal and occipital bone than those of control subjects. The skull thickening was especially noticeable in the frontal bone in moyamoya disease. Plagiocephaly was significantly frequent in moyamoya disease. These uncommon skull shapes are useful CT findings in screening subjects for early evidence of mental diseases and intracranial ischemic diseases with arterial stenosis.


Assuntos
Estenose das Carótidas/patologia , Traumatismos Craniocerebrais/patologia , Transtornos Mentais/patologia , Doença de Moyamoya/patologia , Crânio/anormalidades , Idoso , Feminino , Osso Frontal/anormalidades , Osso Frontal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Osso Occipital/anormalidades , Osso Occipital/patologia , Estudos Retrospectivos , Crânio/patologia , Tomografia Computadorizada por Raios X
6.
Elife ; 102021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313217

RESUMO

Psychoactive drugs can transiently perturb brain physiology while preserving brain structure. The role of physiological state in shaping neural function can therefore be investigated through neuroimaging of pharmacologically induced effects. Previously, using pharmacological neuroimaging, we found that neural and experiential effects of lysergic acid diethylamide (LSD) are attributable to agonism of the serotonin-2A receptor (Preller et al., 2018). Here, we integrate brain-wide transcriptomics with biophysically based circuit modeling to simulate acute neuromodulatory effects of LSD on human cortical large-scale spatiotemporal dynamics. Our model captures the inter-areal topography of LSD-induced changes in cortical blood oxygen level-dependent (BOLD) functional connectivity. These findings suggest that serotonin-2A-mediated modulation of pyramidal-neuronal gain is a circuit mechanism through which LSD alters cortical functional topography. Individual-subject model fitting captures patterns of individual neural differences in pharmacological response related to altered states of consciousness. This work establishes a framework for linking molecular-level manipulations to systems-level functional alterations, with implications for precision medicine.


Assuntos
Encéfalo/efeitos dos fármacos , Dietilamida do Ácido Lisérgico/farmacologia , Transtornos Mentais/tratamento farmacológico , Modelos Teóricos , Transcriptoma , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Encéfalo/fisiopatologia , Estado de Consciência/efeitos dos fármacos , Humanos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia , Neuroimagem/métodos , Receptores 5-HT2 de Serotonina/efeitos dos fármacos
7.
Int J Mol Sci ; 22(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200240

RESUMO

The term neuroinflammation refers to inflammation of the nervous tissue, in general, and in the central nervous system (CNS), in particular. It is a driver of neurotoxicity, it is detrimental, and implies that glial cell activation happens prior to neuronal degeneration and, possibly, even causes it. The inflammation-like glial responses may be initiated in response to a variety of cues such as infection, traumatic brain injury, toxic metabolites, or autoimmunity. The inflammatory response of activated microglia engages the immune system and initiates tissue repair. Through translational research the role played by neuroinflammation has been acknowledged in different disease entities. Intriguingly, these entities include both those directly related to the CNS (commonly designated neuropsychiatric disorders) and those not directly related to the CNS (e.g., cancer and diabetes type 2). Interestingly, all the above-mentioned entities belong to the same group of "complex disorders". This review aims to summarize cumulated data supporting the hypothesis that neuroinflammation is a common denominator of a wide variety of complex diseases. We will concentrate on cancer, type 2 diabetes (T2DM), and neuropsychiatric disorders (focusing on mood disorders).


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Inflamação/complicações , Transtornos Mentais/etiologia , Neoplasias/etiologia , Neurônios/patologia , Animais , Diabetes Mellitus Tipo 2/patologia , Humanos , Transtornos Mentais/patologia , Neoplasias/patologia
8.
J Steroid Biochem Mol Biol ; 213: 105952, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34274458

RESUMO

The impacts of glucocorticoids (GCs) are mainly mediated by a nuclear receptor (GR) existing in almost every tissue. The GR regulates a wide range of physiological functions, including inflammation, cell metabolism, and differentiation playing a major role in cellular responses to GCs and stress. Therefore, the dysregulation or disruption of GR can cause deficiencies in the adaptation to stress and the preservation of homeostasis. The number of GR polymorphisms associated with different diseases has been mounting per year. Tackling these clinical complications obliges a comprehensive understanding of the molecular network action of GCs at the level of the GR structure and its signaling pathways. Beyond genetic variation in the GR gene, epigenetic changes can enhance our understanding of causal factors involved in the development of diseases and identifying biomarkers. In this review, we highlight the relationships of GC receptor gene polymorphisms and epigenetics with different diseases.


Assuntos
Doenças Autoimunes/genética , Doenças Ósseas/genética , Doenças Cardiovasculares/genética , Epigênese Genética , Transtornos Mentais/genética , Doenças Metabólicas/genética , Receptores de Glucocorticoides/genética , Adaptação Fisiológica/genética , Adaptação Fisiológica/imunologia , Animais , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Doenças Ósseas/imunologia , Doenças Ósseas/patologia , Doenças Cardiovasculares/imunologia , Doenças Cardiovasculares/patologia , Metilação de DNA , Glucocorticoides/imunologia , Glucocorticoides/metabolismo , Homeostase/genética , Homeostase/imunologia , Humanos , Inflamação , Transtornos Mentais/imunologia , Transtornos Mentais/patologia , Doenças Metabólicas/imunologia , Doenças Metabólicas/patologia , Polimorfismo Genético , Receptores de Glucocorticoides/química , Receptores de Glucocorticoides/imunologia , Transdução de Sinais , Estresse Fisiológico/genética , Estresse Fisiológico/imunologia
9.
Cells ; 10(6)2021 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205235

RESUMO

Diseases of the central nervous system (CNS) remain a significant health, social and economic problem around the globe. The development of therapeutic strategies for CNS conditions has suffered due to a poor understanding of the underlying pathologies that manifest them. Understanding common etiological origins at the cellular and molecular level is essential to enhance the development of efficacious and targeted treatment options. Over the years, neuroinflammation has been posited as a common link between multiple neurological, neurodegenerative and neuropsychiatric disorders. Processes that precipitate neuroinflammatory conditions including genetics, infections, physical injury and psychosocial factors, like stress and trauma, closely link dysregulation in kynurenine pathway (KP) of tryptophan metabolism as a possible pathophysiological factor that 'fuel the fire' in CNS diseases. In this study, we aim to review emerging evidence that provide mechanistic insights between different CNS disorders, neuroinflammation and the KP. We provide a thorough overview of the different branches of the KP pertinent to CNS disease pathology that have therapeutic implications for the development of selected and efficacious treatment strategies.


Assuntos
Cinurenina/metabolismo , Transtornos Mentais , Doenças Neurodegenerativas , Animais , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/terapia , Transtornos Mentais/metabolismo , Transtornos Mentais/patologia , Transtornos Mentais/terapia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/terapia
10.
J Cell Biol ; 220(7)2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34086051

RESUMO

In a neural circuit, synapses transfer information rapidly between neurons and transform this information during transfer. The diverse computational properties of synapses are shaped by the interactions between pre- and postsynaptic neurons. How synapses are assembled to form a neural circuit, and how the specificity of synaptic connections is achieved, is largely unknown. Here, I posit that synaptic adhesion molecules (SAMs) organize synapse formation. Diverse SAMs collaborate to achieve the astounding specificity and plasticity of synapses, with each SAM contributing different facets. In orchestrating synapse assembly, SAMs likely act as signal transduction devices. Although many candidate SAMs are known, only a few SAMs appear to have a major impact on synapse formation. Thus, a limited set of collaborating SAMs likely suffices to account for synapse formation. Strikingly, several SAMs are genetically linked to neuropsychiatric disorders, suggesting that impairments in synapse assembly are instrumental in the pathogenesis of neuropsychiatric disorders.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Neurogênese/genética , Neurônios/metabolismo , Sinapses/genética , Animais , Transtornos Mentais/genética , Transtornos Mentais/patologia , Neurônios/patologia , Transdução de Sinais/genética , Sinapses/metabolismo , Sinapses/patologia
11.
PLoS One ; 16(5): e0252064, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34015012

RESUMO

PURPOSE: This study aimed to assess the prevalence of common mental disorders and associated factors among adults with glaucoma at Gondar university comprehensive specialized hospital tertiary eye care and training center. Glaucoma predisposes patients to common mental problems and leads to wasteful, costly and inefficient use of medical services and complications of the diagnoses. So, determining the level and factors associated with common mental disorders among glaucoma patient would help to improve and integrate comprehensive ophthalmic services which address common mental disorder in a follow-up visit. METHODS: An institution-based cross-sectional study was conducted on 495 glaucoma patients selected by using systematic random sampling. Data were collected through face-to-face interview and chart review. Self-reported questionnaire (SRQ-20) was used to assess the presence of common mental disorders. Binary logistic regression analysis was done to identify factors associated with common mental disorders. Variables with P<0.05 were considered as factors significantly associated with common mental disorders. RESULT: Four hundred sixty-eight patients were included in this study with a response rate of 94.54%. The mean age of the participant was 58 ± 14.11 years. The prevalence of common mental disorders was found to be 29.5% (95% CI 25.4-33.3). Female sex (AOR = 3.79, 95% CI: 1.66-8.62) (p-value = 0.001), average monthly income of less than 1200 birr (AOR = 6.05 95% CI: 2.26-16.22) (p-value = 0.001), poor level of social support (AOR = 17.39 95% CI: 7.79-38.82) (p-value = 0.001), moderate and high risk of alcohol use (AOR = 10.42 95%CI: 2.74-39.54) (p-value = 0.001), presence of chronic medical illness (AOR = 3.85 95% CI: 2.07-7.16) (p-value = 0.001), receiving both drug and surgical treatment (AOR = 2.50, 95%CI: 1.30-4.83) (p-value = 0.006) and presence of systemic carbonic anhydrase inhibitors use (AOR = 3.16, 95%CI: 1.65-6.06) (p-value = 0.001) were significantly associated with increased level of common mental disorders. CONCLUSION: Significant numbers of glaucoma patients have CMD and found significantly associated with socio-economic, ocular and systemic clinical factors. Therefore, the integration of psychosocial care into the current treatment of patients with glaucoma would have a significant advantage to help these patients.


Assuntos
Depressão/epidemiologia , Glaucoma/epidemiologia , Transtornos Mentais/epidemiologia , Transtornos da Visão/epidemiologia , Adolescente , Adulto , Idoso , Depressão/patologia , Etiópia/epidemiologia , Olho/patologia , Feminino , Glaucoma/complicações , Glaucoma/patologia , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/patologia , Pessoa de Meia-Idade , Fatores de Risco , Inquéritos e Questionários , Centros de Atenção Terciária , Transtornos da Visão/complicações , Transtornos da Visão/patologia , Adulto Jovem
12.
Hum Genet ; 140(8): 1253-1265, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34057592

RESUMO

OBJECTIVE: In the present study, we sought to identify causal relationships between obesity and other complex traits and conditions using a data-driven hypothesis-free approach that uses genetic data to infer causal associations. METHODS: We leveraged available summary-based genetic data from genome-wide association studies on 1498 phenotypes and applied the latent causal variable method (LCV) between obesity and all traits. RESULTS: We identified 110 traits causally associated with obesity. Of those, 109 were causal outcomes of obesity, while only leg pain in calves was a causal determinant of obesity. Causal outcomes of obesity included 26 phenotypes associated with cardiovascular diseases, 22 anthropometric measurements, nine with the musculoskeletal system, nine with behavioural or lifestyle factors including loneliness or isolation, six with respiratory diseases, five with body bioelectric impedances, four with psychiatric phenotypes, four related to the nervous system, four with disabilities or long-standing illness, three with the gastrointestinal system, three with use of analgesics, two with metabolic diseases, one with inflammatory response and one with the neurodevelopmental disorder ADHD, among others. In particular, some causal outcomes of obesity included hypertension, stroke, ever having a period of extreme irritability, low forced vital capacity and forced expiratory volume, diseases of the musculoskeletal system, diabetes, carpal tunnel syndrome, loneliness or isolation, high leukocyte count, and ADHD. CONCLUSIONS: Our results indicate that obesity causally affects a wide range of traits and comorbid diseases, thus providing an overview of the metabolic, physiological, and neuropsychiatric impact of obesity on human health.


Assuntos
Doenças Cardiovasculares/genética , Gastroenteropatias/genética , Pneumopatias/genética , Transtornos Mentais/genética , Doenças Metabólicas/genética , Doenças Musculoesqueléticas/genética , Obesidade/genética , Índice de Massa Corporal , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/patologia , Feminino , Gastroenteropatias/complicações , Gastroenteropatias/patologia , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Solidão/psicologia , Pneumopatias/complicações , Pneumopatias/patologia , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/patologia , Doenças Metabólicas/complicações , Doenças Metabólicas/patologia , Herança Multifatorial , Doenças Musculoesqueléticas/complicações , Doenças Musculoesqueléticas/patologia , Obesidade/complicações , Obesidade/patologia , Fenótipo
13.
Cells ; 10(4)2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33920757

RESUMO

Cholinergic interneurons are "gatekeepers" for striatal circuitry and play pivotal roles in attention, goal-directed actions, habit formation, and behavioral flexibility. Accordingly, perturbations to striatal cholinergic interneurons have been associated with many neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The role of acetylcholine in many of these disorders is well known, but the use of drugs targeting cholinergic systems fell out of favor due to adverse side effects and the introduction of other broadly acting compounds. However, in response to recent findings, re-examining the mechanisms of cholinergic interneuron dysfunction may reveal key insights into underlying pathogeneses. Here, we provide an update on striatal cholinergic interneuron function, connectivity, and their putative involvement in several disorders. In doing so, we aim to spotlight recurring physiological themes, circuits, and mechanisms that can be investigated in future studies using new tools and approaches.


Assuntos
Colinérgicos/metabolismo , Corpo Estriado/patologia , Interneurônios/patologia , Transtornos Mentais/patologia , Degeneração Neural/patologia , Sistema Nervoso/embriologia , Animais , Corpo Estriado/fisiopatologia , Humanos , Transtornos Mentais/fisiopatologia , Degeneração Neural/fisiopatologia , Sistema Nervoso/fisiopatologia
14.
Cell ; 184(8): 1953-1955, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33831377

RESUMO

Mary-Claire King's approach to genetics has had a major impact on breast and ovarian cancer and, more recently, mental illnesses including schizophrenia. Science writer Kendall Morgan talked with Mary-Claire, recipient of a 2021 Canada Gairdner International Award, about her life, her lengthy quest to discover the genetic basis of susceptibility to breast cancer, the struggles for women in science, and much more. An edited version of this conversation is presented below.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Ovarianas/patologia , Distinções e Prêmios , Neoplasias da Mama/genética , Feminino , Genética , Humanos , Transtornos Mentais/genética , Transtornos Mentais/patologia , Neoplasias Ovarianas/genética , Esquizofrenia/genética , Esquizofrenia/patologia
15.
J Korean Med Sci ; 36(15): e96, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33876585

RESUMO

BACKGROUND: Suicide is one of the leading causes of death in the military as in the general population. To mitigate such a serious public health problem, identifying the risk or protective factors of suicide behaviors is crucial. METHODS: We analyzed the representative data of the 2014 Korean Armed Forces to explore the relationship between past year adverse events (PAE), accumulated lifetime trauma (ALT), mental illness vulnerability, perceived social support, and suicidal ideation in the previous year. RESULTS: Among the 6,377 subjects, 3.7% of males and 6.2% of females reported suicidal ideation in the previous year. Multivariate analytic models identified significant associations of PAE and ALT with suicidal ideation with a dose-response pattern. The mental illness vulnerability showed the most significant association with suicidal ideation even after controlling PAE or ALT. We found that perceived social support may be potentially linked with a reduced risk of suicidal ideation. CONCLUSION: This Korean military representative data demonstrates mental illness vulnerability; PAE; and lifetime trauma as significant risk factors of suicidal ideation, while perceived social support was found as a potential protective factor. Given the importance of the prevention of suicide in the military, those risk and protective factors may be used to screen soldiers at risk of suicide and provide further support on mental health services as needed.


Assuntos
Transtornos Mentais/patologia , Militares/estatística & dados numéricos , Apoio Social , Ideação Suicida , Adolescente , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Angústia Psicológica , República da Coreia , Fatores de Risco , Suicídio/prevenção & controle , Transtornos Relacionados a Trauma e Fatores de Estresse/patologia , Adulto Jovem
16.
Biochem J ; 478(7): 1377-1397, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33861845

RESUMO

The salt-inducible kinases, SIK1, SIK2 and SIK3, most closely resemble the AMP-activated protein kinase (AMPK) and other AMPK-related kinases, and like these family members they require phosphorylation by LKB1 to be catalytically active. However, unlike other AMPK-related kinases they are phosphorylated by cyclic AMP-dependent protein kinase (PKA), which promotes their binding to 14-3-3 proteins and inactivation. The most well-established substrates of the SIKs are the CREB-regulated transcriptional co-activators (CRTCs), and the Class 2a histone deacetylases (HDAC4/5/7/9). Phosphorylation by SIKs promotes the translocation of CRTCs and Class 2a HDACs to the cytoplasm and their binding to 14-3-3s, preventing them from regulating their nuclear binding partners, the transcription factors CREB and MEF2. This process is reversed by PKA-dependent inactivation of the SIKs leading to dephosphorylation of CRTCs and Class 2a HDACs and their re-entry into the nucleus. Through the reversible regulation of these substrates and others that have not yet been identified, the SIKs regulate many physiological processes ranging from innate immunity, circadian rhythms and bone formation, to skin pigmentation and metabolism. This review summarises current knowledge of the SIKs and the evidence underpinning these findings, and discusses the therapeutic potential of SIK inhibitors for the treatment of disease.


Assuntos
Ritmo Circadiano , Transtornos Mentais/tratamento farmacológico , Neoplasias/tratamento farmacológico , Osteoporose/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , /antagonistas & inibidores , Humanos , Transtornos Mentais/enzimologia , Transtornos Mentais/patologia , Neoplasias/enzimologia , Neoplasias/patologia , Osteoporose/enzimologia , Osteoporose/patologia
17.
Nanotheranostics ; 5(3): 288-308, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732601

RESUMO

Bio-neuronal led psychiatric abnormalities transpired by the loss of neuronal structure and function (neurodegeneration), pro-inflammatory cytokines, microglial dysfunction, altered neurotransmission, toxicants, serotonin deficiency, kynurenine pathway, and excessively produced neurotoxic substances. These uncontrolled happenings in the etiology of psychiatric disorders initiate further changes in neurotransmitter metabolism, pathologic microglial, cell activation, and impaired neuroplasticity. Inflammatory cytokines, the outcome of dysfunctional mitochondria, dysregulation of the immune system, and under stress functions of the brain are leading biochemical factors for depression and anxiety. Nanoscale drug delivery platforms, inexpensive diagnostics using nanomaterials, nano-scale imaging technologies, and ligand-conjugated nanocrystals used for elucidating the molecular mechanisms and foremost cellular communications liable for such disorders are highly capable features to study for efficient diagnosis and therapy of the mental illness. These theranostic tools made up of multifunctional nanomaterials have the potential for effective and accurate diagnosis, imaging of psychiatric disorders, and are at the forefront of leading technologies in nanotheranostics openings field as they can collectively and efficiently target the stimulated territories of the cerebellum (cells and tissues) through molecular-scale interactions with higher bioavailability, and bio-accessibility. Specifically, the nanoplatforms based neurological changes are playing a significant role in the diagnosis of psychiatric disorders and portraying the routes of functional restoration of mental disorders by newer imaging tools at nano-level in all directions. Because of these nanotherapeutic platforms, the molecules of nanomedicine can penetrate the Blood-Brain Barrier with an increased half-life of drug molecules. The discoveries in nanotheranostics and nanotherapeutics inbuilt unique multi-functionalities are providing the best multiplicities of novel nanotherapeutic potentialities with no toxicity concerns at the level of nano range.


Assuntos
Transtornos Mentais/terapia , Nanomedicina , Medicina de Precisão , Barreira Hematoencefálica , Sistemas de Liberação de Medicamentos , Humanos , Inflamação/patologia , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia
18.
PLoS One ; 16(3): e0248009, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33724987

RESUMO

INTRODUCTION: Since the start of the pandemic, millions of people have been infected, with thousands of deaths. Many foci worldwide have been identified in retirement nursing homes, with a high number of deaths. Our study aims were to evaluate the spread of SARS-CoV-2 in the retirement nursing homes, the predictors to develop symptoms, and death. METHODS AND FINDINGS: We conducted a retrospective study enrolling all people living in retirement nursing homes (PLRNH), where at least one SARS-CoV-2 infected person was present. Medical and clinical data were collected. Variables were compared with Student's t-test or Pearson chi-square test as appropriate. Uni- and multivariate analyses were conducted to evaluate variables' influence on infection and symptoms development. Cox proportional-hazards model was used to evaluate 30 days mortality predictors, considering death as the dependent variable. We enrolled 382 subjects. The mean age was 81.15±10.97 years, and males were 140(36.7%). At the multivariate analysis, mental disorders, malignancies, and angiotensin II receptor blockers were predictors of SARS-CoV-2 infection while having a neurological syndrome was associated with a lower risk. Only half of the people with SARS-CoV-2 infection developed symptoms. Chronic obstructive pulmonary disease and neurological syndrome were correlated with an increased risk of developing SARS-CoV-2 related symptoms. Fifty-six (21.2%) people with SARS-CoV-2 infection died; of these, 53 died in the first 30 days after the swab's positivity. Significant factors associated with 30-days mortality were male gender, hypokinetic disease, and the presence of fever and dyspnea. Patients' autonomy and early heparin treatment were related to lower mortality risk. CONCLUSIONS: We evidenced factors associated with infection's risk and death in a setting with high mortality such as retirement nursing homes, that should be carefully considered in the management of PLRNH.


Assuntos
COVID-19/patologia , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/administração & dosagem , COVID-19/complicações , COVID-19/mortalidade , COVID-19/virologia , Dispneia/etiologia , Feminino , Febre/etiologia , Heparina de Baixo Peso Molecular/uso terapêutico , Humanos , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/patologia , Neoplasias/complicações , Neoplasias/patologia , Casas de Saúde , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Fatores Sexuais , Taxa de Sobrevida
19.
PLoS One ; 16(3): e0247812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33662045

RESUMO

PURPOSE: We addressed prevalence and factors associated with mental health outcomes (suicidal behavior and psychological distress) among Asian Americans (AA), who identify as transgender, a key group among sexual and gender minorities that is overlooked and understudied. METHODS: We used data from 2015 United States Transgender Survey during 2019-2020 with our population as census defined AA. Outcomes included suicidal ideation, suicidal thoughts, and serious psychological distress (SPD). Independent variables included any abuse, partner abuse, bathroom-related abuse, and additional covariates. Adjusted odds ratio and 95% confidence interval (aOR; 95% CI) for each outcome are adjusted for age, marital status, citizenship status, education level, employment status, as well as poverty status. RESULTS: Nearly 67% reported experiencing any abuse, 52% reported abuse from romantic/sexual partner(s), while 29% reported harassment/abuse when trying to use bathrooms. Moreover, 82% reported suicidal thoughts, 40% reported suicidal attempts, and 39% had SPD. Results demonstrated that any abuse/violence had higher odds of suicidal thoughts (adjusted odds ratio [aOR] = 2.67, 95% confidence interval (CI):[1.98-3.58], suicidal attempts (aOR = 2.83, 95% CI:[2.18-3.68]), and SPD (aOR = 1.56, 95% CI:[1.20, 2.04]). Abuse from romantic/sexual partners had higher odds of suicidal thoughts (aOR = 2.47, 95% CI:[1.76-3.47]), suicidal attempts (aOR = 2.17, 95% CI:[1.68-2.80]), and SPD (aOR = 2.72, 95% CI:[2.03-3.63]). Experience of harassment/abuse during bathroom use had increased odds of suicidal attempts (aOR = 1.81, 95% CI:[1.41-2.31]). CONCLUSION: Exposure to violence is common among AA transgender individuals and related to negative mental health outcomes. Initiatives to reduce exposure to abuse and providing resources for trauma-informed care are imperative to improve health outcomes.


Assuntos
/genética , Inquéritos Epidemiológicos/métodos , Transtornos Mentais/psicologia , Avaliação de Resultados em Cuidados de Saúde/métodos , Pessoas Transgênero/psicologia , Violência/estatística & dados numéricos , Adolescente , Adulto , Bases de Dados Factuais , Feminino , Humanos , Masculino , Transtornos Mentais/patologia , Prevalência , Fatores de Risco , Ideação Suicida , Pessoas Transgênero/estatística & dados numéricos , Estados Unidos , Adulto Jovem
20.
Commun Biol ; 4(1): 301, 2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686216

RESUMO

Network architecture is a brain-organizational motif present across spatial scales from cell assemblies to distributed systems. Structural pathology in some neurodegenerative disorders selectively afflicts a subset of functional networks, motivating the network degeneration hypothesis (NDH). Recent evidence suggests that structural pathology recapitulating physiology may be a general property of neuropsychiatric disorders. To test this possibility, we compared functional and structural network meta-analyses drawing upon the BrainMap database. The functional meta-analysis included results from >7,000 experiments of subjects performing >100 task paradigms; the structural meta-analysis included >2,000 experiments of patients with >40 brain disorders. Structure-function network concordance was high: 68% of networks matched (pFWE < 0.01), confirming the broader scope of NDH. This correspondence persisted across higher model orders. A positive linear association between disease and behavioral entropy (p = 0.0006;R2 = 0.53) suggests nodal stress as a common mechanism. Corroborating this interpretation with independent data, we show that metabolic 'cost' significantly differs along this transdiagnostic/multimodal gradient.


Assuntos
Encéfalo/patologia , Encéfalo/fisiopatologia , Transtornos Mentais/patologia , Transtornos Mentais/fisiopatologia , Degeneração Neural , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Mapeamento Encefálico , Estudos de Casos e Controles , Humanos , Transtornos Mentais/diagnóstico por imagem , Transtornos Mentais/metabolismo , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Metanálise em Rede , Doenças Neurodegenerativas/diagnóstico por imagem , Doenças Neurodegenerativas/metabolismo
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