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Background & Objective: Team-Based Learning (TBL) is an interactive instructional approach characterized by collaborative peer teaching in both large and small group settings. The study aims to assess usefulness of the TBL in enhancing student learning outcomes and engagement in graduate classes. Methods: This mixed method study was conducted from January 2023 till July 2023 at the Department of Biological & Biomedical Sciences at Aga Khan University, Karachi, Pakistan, a questionnaire was distributed to graduate students in Endocrine and Reproductive course after TBL on 'Hormonal changes in Pregnancy'. Focus group discussion (FGD) was held with facilitator of this TBL and the students; results of both arms were then triangulated. Results: All (four) students responded affirmatively regarding guided self-preparation, quality of application exercises, satisfaction in terms of student's engagement, a positive attitude and self-accountability. Themes identified by FGD of both students and facilitators were 'Students Engagement in Peer Learning, 'Conducive Learning Environment', "Time is Capital in TBL' and 'Conceptual learning.' Conclusion: The pilot study confirmed the utility of TBL by students as well as the facilitators. Students came with prior preparation, got engaged in problem-solving activities and received feedback from peers and the expert facilitators. The conducive environment enhanced their engagement, enabled them to actively apply the content and benefit from guided supervision.
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Parkinson's disease (PD) and other age-related neurodegenerative ailments have a strong link to oxidative stress. Bioflavonoid naringenin has antioxidant properties. The effects of pre- and post-naringenin supplementation on a rotenone-induced PD model were examined in this work. Naringenin (50 mg/kg, p.o.) was administered to rats for two weeks before the administration of rotenone in the pre-treatment phase. In contrast, rotenone (1.5 mg/kg, s.c.) was administered for eight days before naringenin (50 mg/kg, p.o.) was supplemented for two weeks in the post-treatment phase. During behavioral investigation, the motor and non-motor signs of PD were observed. Additionally, estimation of neurochemical and biochemical parameters was also carried out. Compared to controls, rotenone treatment substantially increased oxidative stress, altered neurotransmitters, and caused motor and non-motor impairments. Rotenone-induced motor and non-motor impairments were considerably reduced by naringenin supplementation. The supplementation also increased antioxidant enzyme activities and restored the changes in neurotransmitter levels. The findings of this work strongly imply that daily consumption of flavonoids such as naringenin may have a therapeutic potential to combat PD.
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Fármacos Neuroprotetores , Transtornos Parkinsonianos , Ratos , Animais , Rotenona/toxicidade , Antioxidantes/farmacologia , Alimento Funcional , Modelos Animais de Doenças , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/tratamento farmacológico , Estresse Oxidativo , Fármacos Neuroprotetores/efeitos adversosRESUMO
Neurological disorders pose significant challenges in terms of treatment options, necessitating the exploration of novel therapeutic approaches. Trigonelline, a naturally occurring alkaloid found in various plants, has emerged as a potential treatment option. It has also been reported that trigonelline is involved in several pathways like; Oxidative Stress and Antioxidant, Inflammatory, Neuroprotection and Neurotrophic, Mitochondrial Function and Energy Metabolism. This study aims to investigate the therapeutic potential of trigonelline for diverse neurological disorders using a molecular docking approach. Molecular docking simulations were performed to predict the binding affinity and interaction between trigonelline and target proteins implicated in neurological disorders. The structural requirements for effective binding were also explored. The molecular docking results revealed strong binding interactions and favorable binding affinities between trigonelline and the target proteins involved in diverse neurological disorders like Alzheimer's disease, Parkinson's disease, epilepsy, and depression etc. The predicted binding modes provided insights into the key molecular interactions governing the ligand-protein complexes. The findings suggest that trigonelline holds promise as a therapeutic approach for several neurological disorders. The molecular docking approach employed in this study provides a valuable tool for rational drug design and optimization of trigonelline-based compounds. Further experimental validation and preclinical studies are warranted to confirm the efficacy and safety of trigonelline as a potential treatment option, paving the way for the development of more effective and targeted therapies for neurological disorders.
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Alcaloides , Doença de Alzheimer , Doenças do Sistema Nervoso , Humanos , Simulação de Acoplamento Molecular , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Doenças do Sistema Nervoso/tratamento farmacológico , Doença de Alzheimer/metabolismoRESUMO
OBJECTIVE: To determine the combined effects of chamomile and saffron herbs as an adjuvant therapy in patients with metabolic alterations associated with mild to moderate depression. METHODS: The prospective, randomised, blinded, end-point pilot study was conducted at the Aga Khan University, Karachi, from August to October 2020, and comprised patients with mild to moderate depression with or without diabetes, hypertension and dyslipidaemia. The subjects were randomised into intervention group A, which was given herbal tea sachets containing saffron 1mg and chamomile 20mg for twice a day oral use for a month along with medications, and control group B, which was advised to continue their routine medications. Data was collected at baseline and post-intervention using Patient Health Questionnaire-9 for assessing depression severity, and blood samples for cholesterol estimations. Data was analysed using SPSS 20. RESULTS: Of the 50 subjects, 25(50%) were in each of the two groups. Cholesterol, high-density lipoprotein, low-density lipoprotein and depression values were significantly better in group A than in group B (p<0.05). CONCLUSIONS: Potential benefits of combined doses of chamomile and saffron were found in depressive patients by improving metabolic alterations.
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Crocus , Humanos , Projetos Piloto , Depressão/tratamento farmacológico , Camomila , Estudos Prospectivos , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacologia , Colesterol , Resultado do Tratamento , Método Duplo-CegoRESUMO
Alzheimer's disease (AD) is the common type of dementia and is currently incurable. Existing FDA-approved AD drugs may not be effective for everyone, they cannot cure the disease nor stop its progression and their effects diminish over time. Therefore, the present review aimed to explore the role of natural alternatives in the treatment of AD. A systematic search was conducted using Ovid MEDLINE, CINAHL, Cochrane and PubMed databases and reference lists up to November 30, 2021. Only randomized control trials were included and appraised using the National Institute of Health framework. Data analysis showed that herbs like Gingko Biloba, Melissa Officinalis, Salvia officinalis, Ginseng and saffron alone or in combination with curcumin, low-fat diet, NuAD-Trail, and soy lecithin showed significant positive effects on AD. Moreover, combination of natural and pharmaceuticals has far better effects than only allopathic treatment. Thus, different herbal remedies in combination with FDA approved drugs are effective and more promising in treatment of AD.
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Doença de Alzheimer , Fitoterapia , Plantas Medicinais , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/terapia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Polymyalgia rheumatica (PMR) is a systemic inflammatory disease of the elderly population that increases in incidence as age advances. It is characterised by the sudden or sub-acute onset of symptoms affecting the shoulder and pelvic girdles, often accompanied by constitutional symptoms. Due to the lack of consensual diagnostic criteria and specific laboratory or radiological investigations for PMR, its diagnosis can be very challenging, particularly because it can be mimicked or masked by other geriatric syndromes. PMR responds well to glucocorticoid treatment, but if left untreated, can lead to morbidity and poor quality of life. We present the case of an 87-year-old male who presented with a one-week history of localised pain in the left hip joint, later involving the contralateral hip. Previously able to ambulate unaided, his mobility was now severely impaired. Due to his Alzheimer's dementia and multiple comorbid geriatric conditions, extensive investigations were undertaken before a diagnosis of atypical PMR was reached. Treatment with a low dose of prednisolone led to a full recovery. This case highlights the inconsistency between an atypical presentation and the classic presentation of PMR and draws attention to the possibility of missed diagnosis in older, frail patients. Atypical symptomatology on top of cognitive impairment and language barriers can be easily overlooked and left untreated and could lead to severe adverse outcomes. Accurate diagnosis is crucial, as PMR is readily diagnosed, but the treatment with glucocorticoids, though generally straightforward, can pose challenges, particularly when dealing with polypharmacy and multiple coexisting health conditions.
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BACKGROUND: The current study utilizes in silico molecular docking/molecular dynamics to evaluate the binding affinity of apigenin and safranal with 5HT1AR/5HT2AR, followed by assessment of in vivo effects of these compounds on depressive and anxious behavior. METHODS: The docking between apigenin and safranal and the 5HT1A and 5HT2A receptors was performed utilizing AutoDock Vina software, while MD and protein-lipid molecular dynamics simulations were executed by AMBER16 software. For in vivo analysis, healthy control (HC), disease control (DC), fluoxetine-, and apigenin-safranal-treated rats were tested for changes in depression and anxiety using the forced swim test (FST) and the elevated plus-maze test (EPMT), respectively. RESULTS: The binding affinity estimations identified the superior interacting capacity of apigenin over safranal for 5HT1A/5HT2A receptors over 200 ns MD simulations. Both compounds exhibit oral bioavailability and absorbance. In the rodent model, there was a significant increase in the overall mobility time in the FST, while in the EPMT, there was a decrease in latency and an increase in the number of entries for the treated and HC rats compared with the DC rats, suggesting a reduction in depressive/anxiety symptoms after treatment. CONCLUSIONS: Our analyses suggest apigenin and safranal as prospective medication options to treat depression and anxiety.
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Apigenina , Simulação de Dinâmica Molecular , Ratos , Animais , Simulação de Acoplamento Molecular , Apigenina/farmacologia , Depressão/tratamento farmacológico , Estudos Prospectivos , Ansiedade/tratamento farmacológico , LipídeosRESUMO
INTRODUCTION: Diabetes mellitus is a chronic metabolic disorder with an increasing prevalence worldwide. Reduction in blood insulin level alters brain function by inducing oxidative stress with changes in dopamine and norepinephrine neurotransmission, ultimately leading to neuropsychological symptoms. The efficacy of currently available psychotropic drugs is not satisfactory. Therefore, this study was conducted to explore the beneficial effects of a combination of the natural herbs, saffron and chamomile, in treating diabetes and its resultant neuropsychological effects using a rodent model of diabetes mellitus. METHOD: The rats were randomly divided in to eight groups (n = 10), healthy control (HC), diabetic control (DC) and six groups of diabetic rats treated with various concentrations and combinations of saffron and chamomile. Diabetic treatment groups individually received methanolic extract and water decoction of chamomile (30 mg/kg) and saffron (10mg/kg) and their combined half doses (saffron 5mg/kg and chamomile 15mg/kg) for two weeks. Open field test (OFT) and forced swim test (FST) were used to measure the anxiolytic and antidepressant effects of herbs, respectively. Finally, biochemical, and neurochemical estimations were made. RESULTS: The present study suggests the therapeutic effects of herbs especially in co-administrated decoction, against diabetes with improved antioxidant profile and enhanced levels of dopamine and norepinephrine. Anxiolytic and antidepressant effects were evident with improvements in the OFT and FST. Examination of the cortex of the diabetic group revealed cellular damage and tangle formation, which indicates advanced stages of dementia. CONCLUSION: This study shows that the use of a combination of saffron and chamomile improves diabetes control and reduces its related psychiatric effects.
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Ansiolíticos , Crocus , Diabetes Mellitus Experimental , Ratos , Camundongos , Animais , Camomila , Diabetes Mellitus Experimental/metabolismo , Ansiolíticos/uso terapêutico , Modelos Animais de Doenças , Dopamina/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Antidepressivos/uso terapêutico , Norepinefrina/uso terapêuticoRESUMO
Depression is one of the common psychiatric problems in growing world population caused by long-term stressful events that may trigger the down regulation of neurogenesis. The pathogenesis of depression initially relies on serotonin deficiency which is associated with depressive feelings. Tryptophan (TRP) depletion participate crucial role in inducing depressive symptoms. Long-term reduction of 5-HT may disseminate to high sensitivity of MDD and alters the level of BDNF. Some studies have also revealed the strong association between excessive neuroinflammation and BDNF levels, due the release of pro-inflammatory cytokines. The treatment approach through FDA approved medicine has their own merits and drawbacks. Therefore, herbal alternatives have recently garnered attention for their effectiveness against depression. However, evidence-based synergic effects of antidepressant with different herbal agents are limited. The purpose of this study was to assess the synergistic effects of two well-known herbs, chamomile and saffron, as an adjuvant therapy in patients with mild to moderate depression. The present study was study randomized, open, blinded trial and comprised of 120 participants randomly allocated to control (n = 60) and test (n = 60). After consent, the patient health questionnaire- 9 (PHQ-9) was filled to obtain depression scores. The test participants were received herbal tea sachets twice a day for one month (20 mg Chamomile and 1 mg Saffron/sachet) along with routine medicines, while control participants were received only allopathic medications. Blood samples were taken before and after the treatment. The depressive symptoms improved significantly with both treatments. The effect of herbs enhanced the efficacy of medications and significantly improved PHQ-9 scale and BDNF while reduced the inflammatory markers (CRP) and TRP level in plasma thereby increased the availability of TRP in brain. It has been concluded that the herbal adjuvant therapy produced long term improvement against depression and enhanced the efficacy of allopathic treatment.
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Fungal transformation of a norethisterone (17α-ethynylestra-4-en-17ß-ol-3-one) (1) by using Macrophomina phaseolina and Paecilomyces variotii was studied. A new metabolite, 17α-hydroxymethyl-androst-4-en-11ß-ol-3-one-17ß-acetate (2) with novel changes and a known metabolite, 17α-ethynylestradiol (3) were obtained from 1 by using M. phaseolina and P. variotii, respectively. Based on various spectroscopic techniques, the structures of both metabolites were characterized. The antimicrobial activities of 1-3 were also evaluated. Compound 1 was found to be moderately active against Salmonella paratyphi while 1-3 were almost inactive against other microorganisms.
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Anti-Infecciosos , Progestinas , Anti-Infecciosos/farmacologia , Biotransformação , Noretindrona/farmacologia , EsteroidesRESUMO
Diabetes is a group of metabolic disorder effecting health of wide number of population and cause neuropsychological decline. In the present study, effect of AI leaves extract on neuropsychological behaviors was observed in diabetic rat's model. Rats were divided into 4 groups as control (saline treated healthy rats), positive control (pioglitazone treated diabetic rats), diabetic control (untreated diabetic rats) and AI leaves extract treated diabetic rats. Diabetes was induced by giving 35% fructose for 6 weeks and a single dose of Streptozotocin (40 mg/kg). After 3 weeks of treatment behavioral and biochemical analysis were done. Behavioral results revealed that induction of type 2 diabetes produced anxiety, depression, decreased motor activity and impaired recognition memory in rats. Treatment with AI leaves extract in diabetic rats significantly decreased anxiety, depression, increased motor activity, enhanced recognition memory. Biochemical investigation revealed that AI leaves extract treat diabetes via improving the levels of fasting insulin and HbA1c and a significant decrease in CK and SGPT levels were observed in AI leaves treated diabetic rats. So, AI besides treating diabetes, helps in lowering the risk of co-occurring diabetic diseases and found effective in lowering neuropsychological decline observed in type 2 diabetes.
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Azadirachta , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Ratos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Transtornos da Memória , Folhas de Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The rotenone-induced animal model of Parkinson's disease (PD) has been used to investigate the pathogenesis of PD. Oxidative stress is one of the main contributors of neurodegeneration in PD. Flavonoids have the potential to modulate neuronal function and combat various neurodegenerative diseases. The pre- and post-supplementation of quercetin (50 mg/kg, p.o) was done in rats injected with rotenone (1.5 mg/kg, s.c). After the treatment, behavioral activities were monitored for motor activity, depression-like behavior, and cognitive changes. Rats were decapitated after behavioral analysis and the brain samples were dissected out for neurochemical and biochemical estimation. Results showed that supplementation of quercetin significantly (p<0.01) restored rotenone-induced motor and non-motor deficits (depression and cognitive impairments), enhanced antioxidant enzyme activities (p<0.01), and attenuated neurotransmitter alterations (p<0.01). It is suggested that quercetin supplementation improves neurotransmitter levels by mitigating oxidative stress via increasing antioxidant enzyme activity and hence improves motor activity, cognitive functions, and reduces depressive behavior. The results of the present study showed that quercetin pre-supplementation produced more significant results as compared to post-supplementation. These findings show that quercetin can be a potential therapeutic agent to reduce the risk and progression of PD.
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Antioxidantes/administração & dosagem , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Depressão/induzido quimicamente , Depressão/tratamento farmacológico , Atividade Motora/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/tratamento farmacológico , Quercetina/administração & dosagem , Rotenona/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/metabolismo , Depressão/metabolismo , Modelos Animais de Doenças , Masculino , Neurotransmissores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson Secundária/metabolismo , Ratos , Ratos Wistar , Rotenona/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
Reserpine (Res)-induced depletion of monoamines and altered neurotransmission and produces oxidative stress. Tryptophan (TRP) regulated the serotonin neurotransmission. Because systemically injected Res induced behavioral deficits and oxidative stress, while, dietary components prevented these adverse effects, we used TRP a pharmacological tool to prevent Res- induced changes in behavior, memory impairments, oxidative stress and regulation of serotonin neurotransmission in rats. Anxiolytic, antidepressant, cognitive functions, lipid peroxidation, antioxidant enzymes serotonin metabolism were studied in Res and vehicle treated animals following administration of 50 and 100 mg/ml/kg of tryptophan. Following administration of TRP [50 and 100mg/ml/kg], Res induced anxiety-and/or depression like behaviors normalized. Res-induced impaired cognitive function and increased acetylcholinesterase activity also improved following administration of TRP at both doses. Res induced increased brains' malondialdehyde (MDA) and decreased antioxidant enzymes activity also normalized by TRP. Res-induced decreased 5-HT metabolism also regulated by administration of TRP at both doses. In conclusion it can be recommended that administration/supplementation of TRP in daily life can aid in battling the anxiety, depression, modulating serotonergic activity and oxidative stress. Study also exhibits the anti-acetylcholinesterase role of TRP which may be possible reason for improved cognition following stress situation.
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Ansiedade/induzido quimicamente , Depressão/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Reserpina/toxicidade , Triptofano/farmacologia , Acetilcolinesterase/metabolismo , Animais , Ansiolíticos , Antidepressivos , Antidepressivos de Segunda Geração , Ansiedade/tratamento farmacológico , Depressão/induzido quimicamente , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Peroxidação de Lipídeos , Transtornos da Memória/induzido quimicamente , Estresse Oxidativo/efeitos dos fármacos , Ratos , Estresse PsicológicoRESUMO
Depressive state adversely affects the memory functions, especially in the geriatric population. The initial stage of memory deficits associated with depression is particularly called as pseudodementia. It is the starting point of memory disturbance before dementia. The purpose of this research was to study depression and its consequent pseudodementia. For this purpose 24 male albino Wistar rats were divided into four groups. Depression was induced by 14 days of chronic restraint stress (CRS) daily for 4 h. After developing a depression model, pattern separation test was conducted to monitor pseudodementia in rats. Morris water maze test (MWM) was also performed to observe spatial memory. It was observed that model animals displayed impaired pattern separation and spatial memory. Treatment was started after the development of pseudodementia in rats. Curcumin at a dose of 200 mg/kg was given to model rats for one week along with the stress procedure. Following the treatment with curcumin, rats were again subjected to the aforementioned behavioral tests before decapitation. Corticosterone levels, brain derived neurotrophic factor (BDNF) and neurochemical analysis were conducted. Model rats showed depressogenic behavior and impaired memory performance. In addition to this, high corticosterone levels and decreased hippocampal BDNF, 5-HT, dopamine (DA), and acetylcholine (ACh) levels were also observed in depressed animals. These behavioral biochemical and neurochemical changes were effectively restored following treatment with curcumin. Hence, it is suggested from this study that pseudodementia can be reversed unlike true dementia by controlling the factors such as depression which induce memory impairment.
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Fator Neurotrófico Derivado do Encéfalo/metabolismo , Curcumina/farmacologia , Depressão/tratamento farmacológico , Dopamina/metabolismo , Transtornos Autoinduzidos/prevenção & controle , Hipocampo/efeitos dos fármacos , Neurotransmissores/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Fator Neurotrófico Derivado do Encéfalo/genética , Corticosterona/metabolismo , Depressão/metabolismo , Depressão/patologia , Transtornos Autoinduzidos/etiologia , Transtornos Autoinduzidos/metabolismo , Transtornos Autoinduzidos/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Masculino , Ratos , Ratos Wistar , Estresse FisiológicoRESUMO
The study is aimed to evaluate the protective impact of banana peel extract (BPE) following noise induce behavioral deficits in male mice. Animals were separated into two groups (control and test, 12 in each). Control mice were given drinking water, at the same time test group was given BPE (400 mg/kg; oral administration). Animals have received their respective treatment for 14 days. Mice were subdivided (n=6) into unstressed and stressed groups on day 15. Noise stress was given to the respective group for 4-h. Behavioral activities were monitored 24-h after the 4-h noise stress. Forced-swim-test, Elevated-plus-maze and light-dark-activity-box tests were performed for depression/anxiety-like behaviors respectively. Morris-water-maze assessment was used for memory. After behavioral tests animals were sacrificed and brain was detached for biochemical estimations and histopathological studies. In the present study, BPE produced anxiolytic and antidepressant-like effects and enhanced memory. Activity of antioxidant enzymes increased while levels of AChE and MDA decreased in BPE treated animals. Histopathological alterations induced by noise stress were also normalized by BPE. It is concluded that supplementation/administration of banana peel has preventive effects against anxiety, depression and memory impairment via its strong antioxidant potential following NS.
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Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Antioxidantes/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Frutas , Musa , Ruído/efeitos adversos , Acetilcolinesterase/metabolismo , Animais , Ansiolíticos/isolamento & purificação , Antidepressivos/isolamento & purificação , Antioxidantes/isolamento & purificação , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Teste de Labirinto em Cruz Elevado , Frutas/química , Proteínas Ligadas por GPI/metabolismo , Locomoção/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Musa/química , Estresse Oxidativo/efeitos dos fármacos , NataçãoRESUMO
OBJECTIVE: To focus mainly on the role of proto-oncogene Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras) and tumour-suppressor gene p53 which are among the most commonly mutated genes in biliary tract carcinomas. METHODS: The systematic review comprised research articles published between 2002 and 2019 on PubMed and Google Scholar databases which were searched using the terms 'TP53', 'K-Ras', 'mutation', 'biliary tract carcinoma', 'cholangiocarcinoma', and 'murine model'. Repetitions, duplicates and irrelevant articles were excluded. No data was retrieved from posters, presentations and symposiums, and experiments involving bile aspirations were also excluded. RESULTS: Of the 72 articles reviewed, 11(15.3%) were included. Of them, 3(27.3%) studies, conducted in China, Japan and Taiwan, reported a positive correlation between K-Ras mutation and biliary tract carcinoma. Only 1(9%) study, conducted in China, showed the sole correlation between p53 inactivation and biliary tract carcinoma. Also, 4(36.4%) studies, conducted in China, Japan and Europe, showed a positive association of both K-Ras mutation and p53 inactivation with biliary tract carcinoma. CONCLUSIONS: K-Ras and p53 mutation both contribute to biliary tract carcinoma. K-Ras mutation, however, has a much higher frequency compared to p53 inactivation in such cancers.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Ductos Biliares Intra-Hepáticos , Genes ras/genética , Camundongos , Mutação , Reação em Cadeia da Polimerase , Proteína Supressora de Tumor p53/genéticaRESUMO
Background: Vocally disruptive behaviour is a common and difficult to treat condition in older residents with dementia. The aim of this systematic review is to evaluate the efficacy of nonpharmacological interventions in its management in persons with dementia residing in a nursing home. Methodology: A systematic search was conducted using Ovid MEDLINE, CINAHL, and Cochrane databases and reference lists from relevant publications on various nonpharmacological approaches to manage vocally disruptive behaviour in nursing home residents. The method of appraisal was through the National Institutes of Health scoring for the Quality Assessment of controlled intervention studies. Inclusion criteria included residents of nursing homes over the age of 65 with dementia and disruptive vocalisation. Only randomised controlled trials published in English were included. Results: A total of 5,606 articles were identified, which cover 501 trials, of which 23 were selected. There were fourteen studies observed to have an impact of clinical and statistical significance with interventions including (i) a multidimensional approach with different nonpharmacological interventions, (ii) multisensory stimulation, (iii) staff education and training, (iv) personalised bathing, and (v) pain recognition and appropriate management. Seven studies demonstrated no observable effect whereas two showed worsening in vocally disruptive behaviour. Conclusions: Many aspects of vocally disruptive behaviour management are poorly understood. Limited empirical evidence supports the use of several nonpharmacological interventions to reduce it. There is more robust evidence to support the use of a tailored approach to management over the universal approach.