RESUMO
INTRODUCTION: The appearance of artificial intelligence language models (AI LMs) in the form of chatbots has gained a lot of popularity worldwide, potentially interfering with different aspects of education, including medical education as well. The present study aims to assess the accuracy and consistency of different AI LMs regarding the histology and embryology knowledge obtained during the 1st year of medical studies. METHODS: Five different chatbots (ChatGPT, Bing AI, Bard AI, Perplexity AI, and ChatSonic) were given two sets of multiple-choice questions (MCQs). AI LMs test results were compared to the same test results obtained from 1st year medical students. Chatbots were instructed to use revised Bloom's taxonomy when classifying questions depending on hierarchical cognitive domains. Simultaneously, two histology teachers independently rated the questions applying the same criteria, followed by the comparison between chatbots' and teachers' question classification. The consistency of chatbots' answers was explored by giving the chatbots the same tests two months apart. RESULTS: AI LMs successfully and correctly solved MCQs regarding histology and embryology material. All five chatbots showed better results than the 1st year medical students on both histology and embryology tests. Chatbots showed poor results when asked to classify the questions according to revised Bloom's cognitive taxonomy compared to teachers. There was an inverse correlation between the difficulty of questions and their correct classification by the chatbots. Retesting the chatbots after two months showed a lack of consistency concerning both MCQs answers and question classification according to revised Bloom's taxonomy learning stage. CONCLUSION: Despite the ability of certain chatbots to provide correct answers to the majority of diverse and heterogeneous questions, a lack of consistency in answers over time warrants their careful use as a medical education tool.
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Inteligência Artificial , Avaliação Educacional , Embriologia , Histologia , Estudantes de Medicina , Embriologia/educação , Humanos , Histologia/educação , Avaliação Educacional/métodos , Educação de Graduação em Medicina/métodosRESUMO
The PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) enzyme interferes with the metabolism of low-density lipoprotein (LDL) cholesterol. Inhibition of PCSK9 results in lower LDL cholesterol levels, which can be achieved by different molecular pathways. Monoclonal antibodies targeting circulating PCSK9 have shown strong and persistent effects on lowering the LDL cholesterol level, while reducing the risk of future cardiovascular events. However, this therapy requires once- or twice-monthly administration in the form of subcutaneous injection. This dosing regimen might impact the therapy adherence in cardiovascular patients who often require multiple drugs with different dosing intervals. Small interfering ribonucleic acid (siRNA) represents a promising therapy approach for patients with elevated LDL cholesterol level despite optimized background statin therapy. Inclisiran is a synthesized siRNA which inhibits PCSK9 synthesis in the liver and provides sustained and durable lowering of LDL cholesterol with twice-yearly application and a good tolerability profile. Herein, we present an overview of the current available data and critical review of the major clinical trials which assessed safety and efficacy of inclisiran in different groups of patients with elevated LDL cholesterol level.
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Anticolesterolemiantes , Pró-Proteína Convertase 9 , Humanos , Pró-Proteína Convertase 9/genética , Pró-Proteína Convertase 9/metabolismo , LDL-Colesterol , RNA Interferente Pequeno/uso terapêutico , Anticolesterolemiantes/efeitos adversosRESUMO
BACKGROUND: To evaluate the significance of visual evoked potentials (VEP) in the early diagnosis of optic neuritis (ON) and detecting clinically silent lesions in pediatric multiple sclerosis (PedMS). This study represents one of the largest series of PedMS which evaluated characteristics of VEP in PedMS patients. METHODS: This was a retrospective study on 52 PedMS patients, aged 7-17 years. VEP analysis were done for all patients, after the first attack of disease and were compared to control subjects according to the pattern-reversal VEP findings. RESULTS: The mean age of patients was 15.65 ± 1.89 years with male to female ratio of 16 (30.8%): 36 (69.2%). All of the patients had a relapsing-remitting course of the disease. ON was discovered on the initial attack in 18 (34.6%) patients, while 30 (57.7%) patients had ON in the second attack. Pathological VEP findings were present in 40 (76.9%) patients, of which 22 (42.3%) PedMS patients had clinically silent lesions. Prolonged latency of P100 waves in the PedMS group was statistically significant when compared to control subjects. The amplitude N1P1 showed a correlation with residual visual deficit. CONCLUSION: Our results show that ON is a common initial manifestation of PedMS in the Serbian PedMS population. The prolonged P100 latency is the main indicator of ON. VEP is an objective, fast and accessible diagnostic method for detecting clinical and subclinical lesions. Thus, VEP deserves evaluation to be considered as an additional criterion for PedMS diagnosis.
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Esclerose Múltipla , Neurite Óptica , Adolescente , Criança , Progressão da Doença , Potenciais Evocados Visuais , Feminino , Humanos , Masculino , Esclerose Múltipla/diagnóstico , Neurite Óptica/diagnóstico , Estudos RetrospectivosRESUMO
Correct interpretation of autopsy findings related to neck structures can be challenging and has tremendous legal importance. We describe a case of a 30-year-old man who was found dead in a hotel courtyard, facedown. The window of his hotel room on the 5th floor was wide open. Police investigation revealed that he was a gambler with many debts, leading them to suspect foul play. The body was transported for a forensic autopsy in a supine position. External examination showed multiple lacerations and contusions of the face and limbs, without signs of external neck injuries. Layer-by-layer neck dissection was unremarkable. Upon opening the pharynx and esophagus, dark purple discoloration of the pharyngeal mucosa could be seen, with a clearly defined margin to the pale circumferential appearance of the rest of the mucosa. To exclude possible tissue bruising due to potential neck compression, histological examination of the mucosa was carried out. Where the mucosa was purple in appearance, there was blood inside the blood vessels, while the vessels of the macroscopically pale mucosa were empty. After forensic autopsy and a detailed police investigation, the manner of death was ruled suicide. In the neck, differential diagnosis between hypostasis and bruising can be especially difficult in rapid, congestive deaths. Forensic pathologists have to be aware of many possible autopsy artifacts in this topographical region, one of those being "banding" of the esophagus. Herein we propose a possible pathophysiological mechanism behind this phenomenon.
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Contusões , Lesões do Pescoço , Suicídio , Adulto , Autopsia , Humanos , Masculino , PescoçoRESUMO
Amyloid plaques, one of the main hallmarks of Alzheimer's disease (AD), are classified into diffuse (associated with cognitive impairment) and dense-core types (a common finding in brains of people without Alzheimer's disease (non-AD) and without impaired cognitive function) based on their morphology. We tried to determine the usability of gray-level co-occurrence matrix (GLCM) texture parameters of homogeneity and heterogeneity for the differentiation of amyloid plaque images obtained from AD and non-AD individuals. Images of amyloid-ß (Aß) immunostained brain tissue samples were obtained from the Aging, Dementia and Traumatic Brain Injury Project. A total of 1,039 plaques were isolated from different brain regions of 69 AD and non-AD individuals and used for further GLCM analysis. Images of Aß stained plaques show higher values of heterogeneity parameters and lower values of homogeneity parameters in AD patients, and vice versa in non-AD patients. Additionally, GLCM analysis shows differences in Aß plaque texture between different brain regions in non-AD patients and correlates with variables that characterize patient's dementia status. The present study shows that GLCM texture analysis is an efficient method to discriminate between different types of amyloid plaques based on their morphology and thus can prove as a valuable tool in the neuropathological investigation of dementia.
Assuntos
Doença de Alzheimer , Placa Amiloide , Envelhecimento , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Humanos , Placa Amiloide/patologiaRESUMO
OBJECTIVE: The present study represents one of the largest series of pediatric multiple sclerosis (PedMS) in Western Balkan region. This is the first study aimed to evaluate the characteristics of PedMS in the Serbian population. METHODS: This retrospective study on 54 PedMS, aged 7-17 years, was performed at the Clinic of Neurology and Psychiatry for Children and Youth in Belgrade, Serbia, a tertiary center for the diagnosis and treatment of children with neurological and psychiatric diseases. RESULTS: Female to male ratio was 37 (68.5%): 17 (31.5%). Family history of MS was noted in 9.3% and autoimmune diseases in 24.1% patients. Co-occurring migraine was in 7,4%. Monofocal onset of disease was present in 77.8% patients. The most common initial symptoms were optic neuritis (37%), sensory disturbances (31.5%), motor deficit (24.1%), cerebellar (18.5%) and brainstem lesions (16.7%), pain (9.3%), acute disseminated encephalomyelitis like symptoms (1.9%), and hearing loss (3.7%). Visual evoked potentials were pathological in 75.9% of patients. Oligoclonal bands were positive in 68.5% of patients. Magnetic resonance imaging showed periventricular (94.4%), infratentorial (77.8%), juxtacortical and cortical changes (55.6%) and changes in the cervical spinal cord (33.3%). The median EDSS score was 2.0. CONCLUSION: Our cohort significantly differs from the literature data regarding more frequent occurrence of optic neuritis, hearing loss as a first symptom, the relapsing-remitting course of the disease, higher proportion of early onset of disease, presence of co-occurring migraine and the frequent occurrence of epilepsy and other autoimmune diseases in the family.
Assuntos
Esclerose Múltipla/diagnóstico , Esclerose Múltipla/terapia , Centros de Atenção Terciária/estatística & dados numéricos , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos RetrospectivosRESUMO
The interpretation of deaths occurring in fires is often complicated by numerous tissue artefacts. The aim of this experimental study was to see whether coronary arteries exposured to heat may have altered morphology. Two specimens of coronary arteries were taken from each of 10 previously healthy men, who died due to trauma, who had no macroscopic evidence of coronary atherosclerosis - one specimen was immediately fixed in formalin (control group), while the other was exposed to high temperature (70°C for five minutes), and then fixed (experimental group). Morphometric analysis of arterial walls showed significant thickening of about 45 % in tissue samples from the experimental group (control vs. experimental: 604.8µm vs. 879.2µm, p<0.002), with much more prominent thickening of the tunica intima and externa (70 % and>50 %), compared to the tunica media (4%). Another feature was either partial or complete loss of the internal elastic lamina in all of the heated arteries. The results of the current study suggest that the morphology of coronary arteries in cases of fire-related deaths should be carefully interpreted, since the thickness of their wall could be increased not due to underlying disease states, but simply due to heat exposure, which may lead to inaccurate pathological interpretations. This may have considerable medicolegal significance if a deceased driver or pilot is being assessed for liability in an accident.
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Vasos Coronários/patologia , Temperatura Alta , Adulto , Túnica Adventícia/patologia , Estudos de Casos e Controles , Incêndios , Patologia Legal , Humanos , Masculino , Microscopia , Túnica Íntima/patologia , Túnica Média/patologia , Adulto JovemRESUMO
Anxiety is one of the most frequent psychiatric disorders. Despite the fact that most studies describe an anxiolytic effect of testosterone, hyperandrogenemia in mothers is assumed to be related to an increased risk of mood disorders in their offspring. An increasing body of scientific evidence suggests that an altered expression of interneuronal markers of the hippocampus may be the cause of anxiety. The aim of this study was to examine the influence of maternal hyperandrogenemia on behavioral parameters of anxiety-like behavior, neuropeptide Y (NPY) and parvalbumin (PV) expression in the hippocampus, and the level of the brain-derived neurotrophic factor (BDNF) in the hippocampus and cerebral cortex. Pregnant female Wistar albino rats were treated with testosterone undecanoate on the 20th day of gestation. Anxiety-like behavior in adult female offspring was evaluated by the elevated plus maze test and the open field. The number of PV and NPY immunoreactive cells in the hippocampus was determined immunohistochemically. The level of BDNF expression in the hippocampus and cerebral cortex was analyzed with the Western blot test. Prenatal hyperandrogenization increased anxiety-like behavior in female offspring and decreased expression of NPY+ and PV+ in the CA1 region of the hippocampus as compared to the control group. BDNF expression in the hippocampus and cerebral cortex of prenatally androgenized female offspring was significantly increased in comparison with the controls. Prenatal hyperandrogenization may be the cause of anxiety-like behavior in female offspring. Decrease in NPY and PV expression in the hippocampus may explain the possible mechanism of hyperandrogenization induced anxiety.
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Ansiedade/etiologia , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Hipocampo/metabolismo , Interneurônios/fisiologia , Inibição Neural/fisiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Virilismo/complicações , Animais , Ansiedade/sangue , Ansiedade/fisiopatologia , Estradiol/sangue , Feminino , Hipocampo/fisiopatologia , Aprendizagem em Labirinto , Neuropeptídeo Y/metabolismo , Parvalbuminas/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/sangue , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos Wistar , Testosterona/administração & dosagem , Testosterona/sangue , Testosterona/farmacologia , Virilismo/fisiopatologiaRESUMO
Previous evidence suggested that lymphocytic thyroiditis (LT) was a variant of Hashimoto's thyroiditis (HT), thus the aim of the current study is to quantify structural changes in histological specimens taken from HT and LT patients. A total of 600 images containing a single lymphocyte nucleus (300 nuclei per group) were obtained from 20 patients with HT and LT. In order to quantify changes in the nuclear architecture of investigated lymphocytes, the fractal dimension (FD) and some gray-level co-occurrence matrix texture parameters (angular second moment, inverse difference moment, contrast, entropy, and correlation) were calculated for each nucleus. A statistically significant difference in the FD of the "binary-outlined" nucleus and that of the corresponding "black-and-white" nucleus was detected between HT and LT lymphocyte nuclei. In addition, there was also a statistically significant difference in contrast and correlation between HT and LT lymphocyte nuclei. In conclusion, the results of this study suggested that there was a difference in structural complexity between investigated lymphocyte nuclei; additionally, LT lymphocytes possessed probably more complex texture and larger variations as well as more asymmetrical nuclei compared with HT lymphocytes. Accordingly, these findings indicate that LT is probably not a variant of HT; however, more complex studies are necessary to estimate differences between these types of thyroiditis.
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Núcleo Celular/patologia , Cromatina/patologia , Fractais , Doença de Hashimoto/patologia , Linfócitos/citologia , Tireoidite Autoimune/patologia , Adulto , Idoso , Algoritmos , Gráficos por Computador , Feminino , Doença de Hashimoto/diagnóstico por imagem , Doença de Hashimoto/terapia , Humanos , Processamento de Imagem Assistida por Computador/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Tireoidite Autoimune/diagnóstico por imagem , Tireoidite Autoimune/terapiaRESUMO
Dysregulation of neurogenesis in the subgranular zone (SGZ) of the hippocampal dentate gyrus has been related to cognitive deficits and memory loss in neurodegenerative diseases, such as Alzheimer's disease (AD). Members of the B group of SOX transcription factors play critical roles in regulating neurogenesis in the embryonic and adult nervous system, including maintaining the multipotency, renewal, and cell fate decision of neural stem/progenitor cells. The aim of the present study was to evaluate the expression patterns of selected SOXB proteins in the SGZ, of 8-week-old male and female 5xFAD mice, which represent a transgenic model of AD with a severe and very early development of amyloid pathology. Immunohistochemical analysis showed a significant decrease in the number of cells expressing SOX1, SOX2, and SOX21 transcription factors within the SGZ of 5xFAD mice in comparison to their non-transgenic counterparts which coincidences with reduced number of doublecortin immunoreactive immature neurons found in Tg males. Despite observed changes in expressional pattern of examined SOXB proteins, the proliferative capacity evaluated by the number of Ki-67 immunoreactive cells remained unaffected in transgenic mice of both genders. Based on our results, we suggest that SOXB proteins might be considered as new biomarkers for the detection of early impairments in adult neurogenesis in different animal models or/and new targets in human regenerative medicine.
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Doença de Alzheimer/metabolismo , Hipocampo/metabolismo , Células-Tronco Neurais/metabolismo , Neurogênese/fisiologia , Neurônios/metabolismo , Fatores de Transcrição SOX/metabolismo , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Feminino , Expressão Gênica , Hipocampo/patologia , Humanos , Antígeno Ki-67/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Células-Tronco Neurais/patologia , Neurônios/patologia , Presenilina-1/genética , Presenilina-1/metabolismoRESUMO
Decreased blood flow in the brain leads to a rapid increase in reactive oxygen species (ROS). NADPH oxidase (NOX) is an enzyme family that has the physiological function to produce ROS. NOX2 and NOX4 overexpression is associated with aggravated ischemic injury, while NOX2/4-deficient mice had reduced stroke size. Dysregulation of matrix metalloproteinases (MMPs) contributes to tissue damage. The active form of vitamin D3 expresses neuroprotective, immunomodulatory, and anti-inflammatory effects in the CNS. The present study examines the effects of the vitamin D3 pretreatment on the oxidative stress parameters and the expression of NOX subunits, MMP9, microglial marker Iba1, and vitamin D receptor (VDR), in the cortex and hippocampus of Mongolian gerbils subjected to ten minutes of global cerebral ischemia, followed by 24 hours of reperfusion. The ischemia/reperfusion procedure has induced oxidative stress, changes in the expression of NOX2 subunits and MMP9 in the brain, and increased MMP9 activity in the serum of experimental animals. Pretreatment with vitamin D3 was especially effective on NOX2 subunits, MMP9, and the level of malondialdehyde and superoxide anion. These results outline the significance of the NOX and MMP9 investigation in brain ischemia and the importance of adequate vitamin D supplementation in ameliorating the injury caused by I/R.
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Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/enzimologia , Colecalciferol/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , NADPH Oxidases/metabolismo , Animais , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Gerbillinae , MasculinoRESUMO
The effects of betaine on hepatocytes chromatin architecture changes were examined by using fractal and gray-level co-occurrence matrix (GLCM) analysis in methionine/choline-deficient (MCD) diet-induced, nonalcoholic fatty liver disease (NAFLD). Male C57BL/6 mice were divided into groups: (1) Control: standard diet; (2) BET: standard diet and betaine supplementation through drinking water (solution 1.5%); (3) MCD group: MCD diet for 6 weeks; (4) MCD+BET: fed with MCD diet + betaine for 6 weeks. Liver tissue was collected for histopathology, immunohistochemistry, and determination of fractal dimension and GLCM parameters. MCD diet induced diffuse micro- and macrovesicular steatosis accompanied with increased Ki67-positive hepatocyte nuclei. Steatosis and Ki67 immunopositivity were less prominent in the MCD+BET group compared with the MCD group. Angular second moment (ASM) and inverse difference moment (IDM) (textural homogeneity markers) were significantly increased in the MCD+BET group versus the MCD group (p<0.001), even though no difference between the MCD and the control group was evident. Heterogeneity parameters, contrast, and correlation were significantly increased in the MCD group versus the control (p<0.001). On the other hand, betaine treatment significantly reduced correlation, contrast, and entropy compared with the MCD group (p<0.001). Betaine attenuated MCD diet-induced NAFLD by reducing fat accumulation and inhibiting hepatocyte proliferation. Betaine supplementation increased nuclear homogeneity and chromatin complexity with reduction of entropy, contrast, and correlation.
Assuntos
Betaína/administração & dosagem , Núcleo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatina/efeitos dos fármacos , Fármacos Gastrointestinais/administração & dosagem , Hepatócitos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Hepatócitos/fisiologia , Histocitoquímica , Imuno-Histoquímica , Antígeno Ki-67/análise , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica/patologiaRESUMO
BACKGROUND: Histopathological changes in the ascending aorta wall in patients with severe tricuspid aortic valve (TAV) stenosis were graded and correlated to echocardiographic parameters. Objective was to associate threshold echocardiographic values with structural defects in the ascending aorta providing a tool to improve decision-making process in cases when simultaneous aortic valve replacement (AVR) and ascending aorta replacement is considered. METHODS: Biopsies from 108 TAV stenosis patients subjected to AVR were graded into three grades according to severity of aortic wall changes. Echocardiographic parameters obtained preoperatively and correlated to grade, age, gender and risk factors, were diameters of ventriculo-aortic junction (AA), sinus Valsalva (SV), sinotubular junction (STJ), the largest diameter of the visualized ascending aorta (AscA) as well as indexes: sinus Valsalva (SVI), sinotubular junction (STJI), AscA/AA and STJ/AA. RESULTS: Two echocardiographic parameters portrayed grades with statistical significance: STJ (F = 5.417; p = 0.006 (p < 0.05)) and AscA (F = 3.924; p = 0.023 (p < 0.05)). By using multiple predictors in the setting of Regression analysis, statistically significant differences among grades were reached for AA, SV, STJ, AscA and SVI. With further ROC curves analysis, threshold values for different grades were recognized. Grade 2 is identified in patients with AscA > 3.3 cm, while Grade 3 is identified in patients with values of AscA > 3.5 cm, STJ > 2.9 cm and STJI > 1. CONCLUSIONS: Hemodynamic stress induced by TAV stenosis leads to elastic lamellae disruption in the aortic wall. Those changes could be graded and correlated with echocardiographic parameters of the aortic root and ascending aorta, providing a tool for decision to replace ascending aorta concomitantly with AVR.
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Aorta/diagnóstico por imagem , Aorta/patologia , Estenose da Valva Aórtica/diagnóstico por imagem , Seio Aórtico/patologia , Idoso , Aorta/cirurgia , Valva Aórtica , Estenose da Valva Aórtica/cirurgia , Tomada de Decisão Clínica , Ecocardiografia , Feminino , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Curva ROC , Fatores de Risco , Seio Aórtico/diagnóstico por imagemRESUMO
The aim of this study was to evaluate the behavioral effects of chronic (six weeks) nandrolone decanoate (ND, 20 mg/kg, s.c., weekly in single dose) administration (in order to mimic heavy human abuse), and exercise (swimming protocol of 60 minutes a day, five days in a row/two days break), applied alone and simultaneously with ND, in male rats (n = 40). Also, we evaluated the effects of those protocols on hippocampal parvalbumin (PV) content and the possible connection between the alterations in certain parts of hippocampal GABAergic system and behavioral patterns. Both ND and exercise protocols induced increase in testosterone, dihydrotestosterone and estradiol blood levels. Our results confirmed anxiogenic effects of ND observed in open field (OF) test (decrease in the locomotor activity, as well as in frequency and cumulative duration in the centre zone) and in elevated plus maze (EPM) test (decrease in frequency and cumulative duration in open arms, and total exploratory activity), that were accompanied with a mild decrease in the number of PV interneurons in hippocampus. Chronic exercise protocol induced significant increase in hippocampal PV neurons (dentate gyrus and CA1 region), followed by anxiolytic-like behavioral changes, observed in both OF and EPM (increase in all estimated parameters), and in evoked beam-walking test (increase in time to cross the beam), compared to ND treated animals. The applied dose of ND was sufficient to attenuate beneficial effects of exercise in rats by means of decreased exercise-induced anxiolytic effect, as well as to reverse exercise-induced augmentation in number of PV immunoreactive neurons in hippocampus. Our results implicate the possibility that alterations in hippocampal PV interneurons (i.e. GABAergic system) may be involved in modulation of anxiety level induced by ND abuse and/or extended exercise protocols.
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Hipocampo/efeitos dos fármacos , Interneurônios/metabolismo , Nandrolona/análogos & derivados , Parvalbuminas/metabolismo , Condicionamento Físico Animal , Animais , Comportamento Animal/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Nandrolona/farmacologia , Decanoato de Nandrolona , Ratos , Ratos WistarRESUMO
INTRODUCTION: A prospective interventional study has been carried out on the teaching effect and sustainability of low-cost trauma training program in open tibia fracture management for health workers. MATERIALS AND METHODS: In 2007, an external fixator and a patella-bearing orthosis were developed at a rural workshop in Cambodia. From 2010 to 2016, a core group of nine Cambodian health workers was trained in open fracture management by Norwegian senior surgeons, using the locally made fixator and brace. The training outcome was also assessed by a questionnaire comprising of assertions regarding theoretical understanding, technical skills and self-confidence in understanding the biomechanical properties of locally made external fixator and its application; the use of handmade orthosis and principle in covering of soft-tissue defects. RESULTS: The students managed 23 cases with the new technique with a primary healing rate of 70% (95% CI 48.1-85.5). A significant increase in self-reported technical skills, understanding, and self-confidence was reported. CONCLUSION: This study demonstrates that the capacity building of reconstructive surgery in low-resource settings by local doctors and paramedics is clearly a reasonable option that may substantially reduce amputation of the limbs.
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Fixadores Externos , Fraturas Expostas/cirurgia , Pessoal de Saúde/educação , Aparelhos Ortopédicos , Fraturas da Tíbia/cirurgia , Camboja , Recursos em Saúde , Hospitais Rurais , Humanos , Estudos Prospectivos , CicatrizaçãoRESUMO
The administration of dexamethasone, a synthetic glucocorticoid receptor agonist, has been reported to modulate cognitive performance in both animals and humans. In the present study, we demonstrate the effects of a single high dose of dexamethasone on the expression and distribution of synaptic plasticity-related proteins, growth-associated protein-43 (GAP-43) and synaptophysin, in the hippocampus of 6-, 12-, 18- and 24-month-old rats. Acute dexamethasone treatment significantly altered the expression of GAP-43 at the posttranslational level by modulating the levels of phosphorylated GAP-43 and proteolytic GAP-43-3 fragment. The effect was the most pronounced in the hippocampi of the aged animals. The total GAP-43 protein was increased only in 24-month-old dexamethasone-treated animals, and was concomitant with a decrease in calpain-mediated proteolysis. Moreover, by introducing the gray level co-occurrence matrix method, a form of texture analysis, we were able to reveal the subtle differences in the expression pattern of both GAP-43 and synaptophysin in the hippocampal subfields that were not detected by Western blot analysis alone. Therefore, the current study demonstrates, through a novel combined approach, that dexamethasone treatment significantly affects both GAP-43 and synaptophysin protein expression in the hippocampus of aged rats.
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Dexametasona/administração & dosagem , Proteína GAP-43/metabolismo , Glucocorticoides/administração & dosagem , Hipocampo/efeitos dos fármacos , Sinaptofisina/metabolismo , Fatores Etários , Envelhecimento/metabolismo , Animais , Calpaína/metabolismo , Hipocampo/metabolismo , Masculino , Fosforilação , Proteólise , Ratos Wistar , Regulação para CimaRESUMO
Exposure of an organism to chronic psychosocial stress may affect brain-derived neurotrophic factor (BDNF) expression that has been implicated in the etiology of psychiatric disorders, such as depression. Given that depression in humans has been linked with social stress, the chronic social stress paradigms for modeling psychiatric disorders in animals have thus been developed. Chronic social isolation in animal models generally causes changes in hypothalamic-pituitary-adrenal axis functioning, associated with anxiety- and depressive-like behaviors. Also, this chronic stress causes downregulation of BDNF protein and mRNA in the hippocampus, a stress-sensitive brain region closely related to the pathophysiology of depression. In this review, we discuss the current knowledge regarding the structure, function, intracellular signaling, inter-individual differences and epigenetic regulation of BDNF in both physiological conditions and depression and changes in corticosterone levels, as a marker of stress response. Since BDNF levels are age dependent in humans and rodents, this review will also highlight the effects of adolescent and adult chronic social isolation models of both genders on the BDNF expression.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Transtorno Depressivo/metabolismo , Hipocampo/metabolismo , Isolamento Social , Estresse Psicológico/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/química , Fator Neurotrófico Derivado do Encéfalo/genética , Transtorno Depressivo/etiologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Humanos , Estresse Psicológico/etiologiaRESUMO
Since the increased prevalence of anabolic androgenic steroids abuse in last few decades is usually accompanied by various exercise protocols, the scope of our study was to evaluate the effects of chronic nandrolone decanoate administration in supraphysiological dose and a prolonged swimming protocol (alone and simultaneously with nandrolone decanoate) on depressive state in male rats. Simultaneously, we investigated the possible alterations in neuropeptide Y (NPY) content in blood and the hippocampus, in order to determine the role of NPY in the modulation of depressive-like behavior.Exercise induced antidepressant effects in tail suspension test (decrease of the total duration of immobility), as well as significant increase in the number of hippocampal NPY-interneurons in CA1 region. Chronic nandrolone decanoate treatment attenuated the beneficial antidepressant effects of exercise as measured by the tail suspension test parameters. Simultaneously, nandrolone decanoate treatment resulted in diminution of NPY content both in blood (decreased serum levels) and in hippocampus (the significant decrease in NPY expression in all three investigated hippocampal regions-CA1, CA2/3 and DG). Our findings indicate that alterations in serum and hippocampal NPY contents may underlie the changes in depressive state in rats. The exercise was beneficial as it exerted antidepressant effect, while chronic nandrolone decanoate treatment resulted in depressive-like behavior. Furthermore, the behavioral indicators of depression showed strong correlations with the serum levels and the hippocampal content of NPY.
Assuntos
Anabolizantes/efeitos adversos , Depressão/metabolismo , Expressão Gênica/efeitos dos fármacos , Nandrolona/análogos & derivados , Neuropeptídeo Y/metabolismo , Condicionamento Físico Animal , Animais , Comportamento Animal/efeitos dos fármacos , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA2 Hipocampal/efeitos dos fármacos , Região CA2 Hipocampal/metabolismo , Região CA3 Hipocampal/efeitos dos fármacos , Região CA3 Hipocampal/metabolismo , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Depressão/genética , Depressão/fisiopatologia , Imobilização , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Masculino , Nandrolona/efeitos adversos , Decanoato de Nandrolona , Neuropeptídeo Y/antagonistas & inibidores , Neuropeptídeo Y/genética , Ratos , Ratos Wistar , NataçãoRESUMO
In recent years, electromagnetic field (EMF) and low-level laser (LLL) have been found to affect various biological processes, the growth and proliferation of cells, and especially that of stem cells. The aim of this study was to investigate the effects of EMF and LLL on proliferation of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and thus to examine the impact of these therapeutic physical modalities on stem cell engraftment. hAT-MSCs were isolated from subcutaneous adipose tissue of six persons ranging in age from 21 to 56 years. EMF was applied for a period of 7 days, once a day for 30 min, via a magnetic cushion surface at a frequency of 50 Hz and an intensity of 3 mT. LLL was applied also for 7 days, once a day for 5 min, at radiation energies of 3 J/cm2, with a wavelength of 808 nm, power output of 200 mW, and power density of 0.2 W/cm2. Nonexposed cells (control) were cultivated under the same culture conditions. Seven days after treatment, the cells were examined for cell viability, proliferation, and morphology. We found that after 7 days, the number of EMF-treated hAT-MSCs was significantly higher than the number of the untreated cells, LLL-treated hAT-MSCs were more numerous than EMF-treated cells, and hAT-MSCs that were treated with the combination of EMF and LLL were the most numerous. EMF and/or LLL treatment did not significantly affect hAT-MSC viability by itself. Changes in cell morphology were also observed, in terms of an increase in cell surface area and fractal dimension in hAT-MSCs treated with EMF and the combination of EMF and LLL. In conclusion, EMF and/or LLL treatment accelerated the proliferation of hAT-MSCs without compromising their viability, and therefore, they may be used in stem cell tissue engineering.