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The neurobiology of Alzheimer's disease (AD) is unclear due to its multifactorial nature. Although a wide range of studies revealed several pathomechanisms of AD, dementia is yet unmanageable with current pharmacotherapies. The recent growing literature illustrates the role of microglia-mediated neuroinflammation in the pathogenesis of AD. Indeed, microglia serve as predominant sentinels of the brain, which diligently monitor the neuroimmune axis by phagocytosis and releasing soluble factors. In the case of AD, microglial cells are involved in synaptic pruning and remodeling by producing inflammatory mediators. The conditional inter-transformation of classical activation (proinflammatory) or alternative activation (anti-inflammatory) microglia is responsible for most brain disorders. In this review, we discussed the role of microglia in neuroinflammatory processes in AD following the accumulation of amyloid-ß and tau proteins. We also described the prominent phenotypes of microglia, such as disease-associated microglia (DAM), dark microglia, interferon-responsive microglia (IRMs), human AD microglia (HAMs), and microglial neurodegenerative phenotype (MGnD), which are closely associated with AD incidence. Considering the key role of microglia in AD progression, microglial-based therapeutics may hold promise in mitigating cognitive deficits by addressing the neuroinflammatory responses.
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BACKGROUND: Among the three most used anticancer drugs, cyclophosphamide, Adriamycin, and 5-Fluorouracil (CAF), the most significant outcome is chemobrain, caused by increased oxidative stress, inflammatory insult, and mitochondrial dysfunction. OBJECTIVE: In this study, endogenous antioxidant coenzyme Q10 (CoQ10) was evaluated for its neuroprotective effects in CICI. MATERIALS AND METHODS: The chemobrain was induced in Swiss albino female mice by administering CAF (40 + 4 + 25 mg/kg) intraperitoneal (i.p.) in three cycles (single injection per week) followed by treatment with CoQ10 (40 mg/kg; p.o.) for up to 3 weeks followed by behavioral, biochemical, molecular and histopathological analysis. RESULTS: Treatment with CoQ10 significantly improved cognition by improving exploring time in novel objects recognition test followed by increasing the time spent in the target quadrant in MWM test as compared to CAF-treated animals. Moreover, CoQ10 demonstrated antioxidant properties by reducing the expression of LPO while increasing levels of GSH, SOD, and catalase as compared to CAF-treated animals. While the levels of AChEs were significantly reduced after CoQ10 treatment in CAF-treated animals. In terms of its mechanism, it effectively counteracted the pro-inflammatory substances (TNF-α and IL-1ß) triggered by CAF while also enhancing the levels of anti-inflammatory markers (IL-10 and Nrf2). Moreover, CoQ10 showed mitochondrial enhancers and it improved the level of Complex (I, II, and IV). Besides that, mitochondrial morphological analysis was done by TEM, and neuronal morphology along with quantification analysis was performed by H&E staining using Image J software to confirm the neuroprotective effect of CoQ10 over CAF-induced cognitive impairment. CONCLUSION: This study suggests CoQ10 can protect the mitochondria by imposing antioxidant, and anti-inflammatory properties, which could be a potential therapy for CICI.
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Antioxidantes , Estresse Oxidativo , Ubiquinona , Animais , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico , Camundongos , Feminino , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Comprometimento Cognitivo Relacionado à Quimioterapia/tratamento farmacológico , Comprometimento Cognitivo Relacionado à Quimioterapia/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Doxorrubicina/efeitos adversos , Fluoruracila/efeitos adversos , Fluoruracila/farmacologia , Modelos Animais de Doenças , Antineoplásicos/farmacologia , Antineoplásicos/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacologiaRESUMO
Today, we critically need alternative therapeutic options for chemotherapy-induced cognitive impairment (CICI), often known as chemo brain. Mitochondrial dysfunction and oxidative stress are two of the primary processes that contribute to the development of chemobrain. Therefore, the purpose of this study was to investigate how CoQ10 and berberine shield neurons from chemotherapy-induced damage in in-vitro studies and memory loss in vivo studies. For the in-vitro investigation, we employed SH-SY5Y cell lines, and for the in-vivo study, we used female Swiss albino mice divided into seven different groups. Data from in-vitro studies revealed that treatment with coenzyme Q10 (CoQ10) and berberine improved chemotherapy-induced toxicity by reducing mitochondrial and total cellular ROS, as well as apoptosis-elicited markers (caspase 3 and 9). CoQ10 and berberine therapy inhibited the nuclear translocation of NF-κB and, consequently, the subsequent expressions of NLRP3 and IL-1ß, implying the prevention of inflammasome formation. Furthermore, CoQ10 and berberine therapy boosted Nrf2 levels. This is a regulator for cellular resistance to oxidants. The in vivo results showed that treatment with CoQ10 (40 mg/kg) and berberine (200 mg/kg) improved the behavioral alterations induced by CAF (40/4/25 mg/kg) in both the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Furthermore, biochemical and molecular evidence revealed the antioxidant, mitochondrial restorative, and anti-inflammatory potential of CoQ10 (40 mg/kg) and berberine (200 mg/kg) against CAF (40/4/25 mg/kg) subjected mice. In addition, the histological analysis using H&E staining and transmission electron microscopy (for mitochondrial morphology) showed that mice treated with the cocktails had an increased number of healthy neurons with intact mitochondria and a reduced presence of autophagic vacuoles in the hippocampal region of the brain. These findings back up our theory about this novel cocktail method for CAF-induced cognitive impairment.
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Berberina , Fator 2 Relacionado a NF-E2 , NF-kappa B , Transdução de Sinais , Ubiquinona , Animais , NF-kappa B/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Feminino , Fator 2 Relacionado a NF-E2/metabolismo , Berberina/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Ubiquinona/administração & dosagem , Humanos , Linhagem Celular Tumoral , Estresse Oxidativo/efeitos dos fármacos , Comprometimento Cognitivo Relacionado à Quimioterapia/metabolismo , Comprometimento Cognitivo Relacionado à Quimioterapia/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Apoptose/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismoRESUMO
In recent years, research into the complex interactions and crosstalk between plants and their associated microbiota, collectively known as the plant microbiome has revealed the pivotal role of microbial communities for promoting plant growth and health. Plants have evolved intricate relationships with a diverse array of microorganisms inhabiting their roots, leaves, and other plant tissues. This microbiota mainly includes bacteria, archaea, fungi, protozoans, and viruses, forming a dynamic and interconnected network within and around the plant. Through mutualistic or cooperative interactions, these microbes contribute to various aspects of plant health and development. The direct mechanisms of the plant microbiome include the enhancement of plant growth and development through nutrient acquisition. Microbes have the ability to solubilize essential minerals, fix atmospheric nitrogen, and convert organic matter into accessible forms, thereby augmenting the nutrient pool available to the plant. Additionally, the microbiome helps plants to withstand biotic and abiotic stresses, such as pathogen attacks and adverse environmental conditions, by priming the plant's immune responses, antagonizing phytopathogens, and improving stress tolerance. Furthermore, the plant microbiome plays a vital role in phytohormone regulation, facilitating hormonal balance within the plant. This regulation influences various growth processes, including root development, flowering, and fruiting. Microbial communities can also produce secondary metabolites, which directly or indirectly promote plant growth, development, and health. Understanding the functional potential of the plant microbiome has led to innovative agricultural practices, such as microbiome-based biofertilizers and biopesticides, which harness the power of beneficial microorganisms to enhance crop yields while reducing the dependency on chemical inputs. In the present review, we discuss and highlight research gaps regarding the plant microbiome and how the plant microbiome can be used as a source of single and synthetic bioinoculants for plant growth and health.
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Agricultura , Bactérias , Microbiota , Desenvolvimento Vegetal , Plantas , Microbiota/fisiologia , Plantas/microbiologia , Agricultura/métodos , Bactérias/metabolismo , Bactérias/classificação , Raízes de Plantas/microbiologia , Simbiose , Fungos/metabolismo , Fungos/fisiologia , Reguladores de Crescimento de Plantas/metabolismo , Microbiologia do SoloRESUMO
BACKGROUND: The COVID-19 pandemic has affected the availability and access to medications for opioid dependence (OD). We examined the monthly trends in new buprenorphine/naloxone (BNX) treatment episodes, number of clinical visits for BNX, BNX dispensed per person, and BNX prescription over 56-month, which included pre-pandemic, during early, and later part of pandemic (Jan 2017 - Aug 2022). METHODS: Research data were collected from the pharmacy database of a large publicly funded treatment center in India. A flexible, low-threshold service was adopted in April 2020 in response to the lockdown implemented on 25 March 2020. Change Point analyses were performed to examine monthly trends visually and statistically. We used Autoregressive integrated moving averages to forecast trends from April to Aug 2020 and March to August 2022, using Jan 2017 to March 2020 and March 2020 to February 2022 as training datasets. RESULTS: 993 patients were started on BNX treatment, 40452 BNX clinic attendances were made, 1401393 BNX tablets were dispensed, and 6795 new patients with OD were registered. The observed data for clinic attendance for BNX was significantly lower than the projected estimates in April -Aug 2020; however, observed new treatment episodes and monthly BNX prescriptions were within the 95% projected estimates; BNX dispensed per person was significantly more than the projected estimate. In contrast, observed BNX prescription trends surpassed the upper limit of 95% CI in March-Aug 2022. CONCLUSION: A low-threshold and flexible treatment service could mitigate the unintended consequences of pandemic-induced restrictions.
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Chemotherapy-induced cognitive impairment (CICI), also known as "chemobrain," is a common side effect of breast cancer therapy which causes oxidative stress and generation of reactive oxygen species (ROS). Ferulic acid (FA), a natural polyphenol, belongs to BCS class II is confirmed to have nootropic, neuroprotective and antioxidant effects. Here, we have developed FA solid dispersion (SD) in order to enhance its therapeutic potential against chemobrain. An amorphous ferulic acid loaded leucin solid dispersion (FA-Leu SD) was prepared by utilizing amino acid through spray-drying technique. The solid-state characterization was carried out via Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and field emission scanning electron microscopy (FE-SEM). Additionally, in-vitro release studies and antioxidant assay were also performed along with in-vivo locomotor, biochemical and histopathological analysis. The physical properties showed that FA-Leu SD so formed exhibited spherical, irregular surface hollow cavity of along with broad melting endotherm as observed from FE-SEM and DSC results. The XRD spectra demonstrated absence of sharp and intense peaks in FA-Leu SD which evidenced for complete encapsulation of drug into carrier. Moreover, in-vitro drug release studies over a period of 5 h in PBS (pH 7.4) displayed a significant enhanced release in the first hr (68. 49 ± 5.39%) and in-vitro DPPH assay displayed greater antioxidant potential of FA in FA-Leu SD. Furthermore, the in-vivo behavioral findings of FA-Leu SD (equivalent to 150 mg/kg of free FA) exhibited positive results accompanied by in-vivo biochemical and molecular TNF-α showed a significant difference (p < 0.001) vis-à-vis DOX treated group upon DOX + FA-Leu SD. Additionally, histopathological analysis revealed neuroprotective effects of FA-Leu SD together with declined oxidative stress due to antioxidant potential of FA which was induced by anticancer drug doxorubicin (DOX). Overall, the above findings concluded that spray-dried FA-Leu SD could be useful for the treatment of chemotherapy induced cognitive impairment.
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Background: Sepsis, the second most common cause of neonatal mortality, causes more than one million deaths annually. India has the highest incidence of clinical sepsis (17000/100000 live birth). Objective: This study aimed to determine the risk factors and organisms of early-onset neonatal sepsis (EONS) in a tertiary care hospital in Northeast India. Materials and Methods: It was a case-control study conducted in the neonatal unit of MGM Medical College, Kishanganj, Bihar, from January 2022 to April 2023. All neonates admitted to the neonatal intensive care unit (NICU) within 72 hours of life constituted the study population. Neonates diagnosed as EONS by clinical and laboratory parameters were considered as cases and those not diagnosed for EONS as controls. Maternal and newborn information and laboratory parameters were collected and analyzed. For risk factor identification, the bivariate logistic regression was used. Result: An equal number of cases (78) and control (78) were enrolled in the study. Maternal age >30 years (adjusted odds ratio [aOR] = 3.017, confidence interval [CI]: 1.238 to 7.352; P < 0.015), maternal urinary tract infection (UTI) in the third trimester (aOR = 5.435, CI: 2.647 to 11.158; P < 0.0001), and premature rupture of membranes (PROM) (aOR = 2.918, CI: 4.61 to 33.73, P < 0.004) were significant predictors of EONS. Pseudomonas (41.02%), Klebsiella (16.66%), and coagulase-negative Staphylococcus aureus (20.51%) were commonly isolated organisms, which were highly resistant to cephalosporin, meropenem, aminoglycosides, and quinolones. Conclusion: Proper and adequate antenatal screening for diagnosis and treatment of maternal infection and high-risk pregnancies for perinatal management of newborn is recommended to prevent neonatal sepsis-related morbidity and mortality. Rational use of antibiotics may minimize the hazard of antibiotic resistance.
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Autophagy is a self-destructive cellular process that removes essential metabolites and waste from inside the cell to maintain cellular health. Mitophagy is the process by which autophagy causes disruption inside mitochondria and the total removal of damaged or stressed mitochondria, hence enhancing cellular health. The mitochondria are the powerhouses of the cell, performing essential functions such as ATP (adenosine triphosphate) generation, metabolism, Ca2+ buffering, and signal transduction. Many different mechanisms, including endosomal and autophagosomal transport, bring these substrates to lysosomes for processing. Autophagy and endocytic processes each have distinct compartments, and they interact dynamically with one another to complete digestion. Since mitophagy is essential for maintaining cellular health and using genetics, cell biology, and proteomics techniques, it is necessary to understand its beginning, particularly in ubiquitin and receptor-dependent signalling in injured mitochondria. Despite their similar symptoms and emerging genetic foundations, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) have all been linked to abnormalities in autophagy and endolysosomal pathways associated with neuronal dysfunction. Mitophagy is responsible for normal mitochondrial turnover and, under certain physiological or pathological situations, may drive the elimination of faulty mitochondria. Due to their high energy requirements and post-mitotic origin, neurons are especially susceptible to autophagic and mitochondrial malfunction. This article focused on the importance of autophagy and mitophagy in neurodegenerative illnesses and how they might be used to create novel therapeutic approaches for treating a wide range of neurological disorders.
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Doença de Alzheimer , Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Mitofagia/fisiologia , Autofagia/fisiologia , Doenças Neurodegenerativas/metabolismo , Doença de Alzheimer/metabolismo , Doença de Parkinson/metabolismoRESUMO
Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.
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Nanopartículas , Neoplasias , Humanos , Polímeros/química , Polímeros/uso terapêutico , Sistemas de Liberação de Medicamentos , Polietilenoglicóis/química , Neoplasias/tratamento farmacológico , Imunoterapia , Nanopartículas/química , Microambiente TumoralRESUMO
Antibodies reactive with the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein are associated with viral neutralization, however low antibody titers, specifically against SARS-CoV-2 variants, may result in reduced viral immunity post naturally acquired infection. A cohort study comprised of 121 convalescent individuals from northern Nevada was conducted looking at anti-RBD antibody levels by enzyme-linked immunosorbent assay. Serum was collected from volunteers by staff at the University of Nevada, Reno School of Medicine Clinical Research Center and assessed for antibodies reactive to various SARS-CoV-2 RBD domains relevant to the time of the study (2020-2021). A nonpaired group of vaccinated individuals were assessed in parallel. The goal of the study was to identify antibody levels against the RBD subunit in convalescent and vaccinated individuals from northern Nevada.
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COVID-19 , SARS-CoV-2 , Humanos , Estudos de Coortes , Nevada , Anticorpos , Anticorpos Antivirais , Glicoproteína da Espícula de Coronavírus , Anticorpos NeutralizantesRESUMO
PURPOSE OF REVIEW: The incidence of hypertensive disorders of pregnancy (HDP), especially preeclampsia has increased significantly over the last two decades. Patients with these disorders often report cerebral and visual symptoms, which are listed as potential diagnosis criteria for preeclampsia, if accompanied by new-onset hypertension. Recent studies indicate that cerebral complications in HDP patients are associated with a compromised blood-brain barrier (BBB). The purpose of this review is to highlight the recent literature focused on the BBB in HDP, identify gaps in knowledge, and discuss future directions in this research area. RECENT FINDINGS: Majority of the studies addressing BBB changes in HDP are focused on preeclampsia. Recent studies show that hypertension induces increased association of perivascular macrophages/microglia to the cerebral vessels, increased circulating extracellular vesicles, and decreased autoregulation of cerebral blood flow. There is a critical need for more animal studies targeted to protecting the BBB and preventing cerebrovascular complications in the context of HDP. More clinical studies are needed that investigate both the short- and long-term interplay between each HDP subtype and BBB and cognitive function.
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Sistema Cardiovascular , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Gravidez , Feminino , Animais , Humanos , Barreira Hematoencefálica , Circulação CerebrovascularRESUMO
BACKGROUND: Google Trends provides an easily accessible and cost-effective method of providing real-time insight into user interest. OBJECTIVE: to address the gap in UK prevalence data for e-cigarettes by analyzing Google Trends to identify correlations with official data from Action on Smoking and Health. The study further evaluates Google Trend's sensitivity to real-time events and the ability for predictive models to forecast future data based on Google Trends. METHODS: UK Google Trends data from 2012 to 2021 was analyzed to assess (a) the most popular electronic nicotine device terminology; (b) statistically significant points in time; (c) correlations between Relative Search Volumes and official reports on electronic cigarette use and (d) whether Google Trends could predict future patterns in data. These were achieved using Locally Weighted Scatterplot Smoothing regression, Pruned Exact Linear Time Method, cross correlation, and Autoregressive Integrated Moving Average algorithms respectively. RESULTS: "Vape" was revealed to be the most popular electronic nicotine device terminology with a correlation coefficient greater than +0.9 when compared to official electronic cigarette consumption data within a one-year timescale (lag 0). Results from ARIMA modeling were varied with the algorithms forecasted trends line occasionally lying outside of a 95% prediction interval. CONCLUSION: Google Trends may correspond to population-based prevalence of electronic cigarette use. The changing trends coincide with changing policy decisions. Google Trends based prediction for online interest in electronic cigarettes requires further validation so should currently be used in conjunction with other traditional methods of data collections.
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Sistemas Eletrônicos de Liberação de Nicotina , Humanos , Nicotina , Ferramenta de Busca/métodos , Coleta de Dados , Reino Unido/epidemiologiaRESUMO
BACKGROUND & AIM: Obesity is a worldwide epidemic leading to decreased quality of life, higher medical expenses and significant morbidity. Enhancing energy expenditure and substrate utilization in adipose tissues through dietary constituents and polypharmacological approaches is gaining importance for the prevention and therapeutics of obesity. An important factor in this regard is Transient Receptor Potential (TRP) channel modulation and resultant activation of "brite" phenotype. Various dietary TRP channel agonists like capsaicin (TRPV1), cinnamaldehyde (TRPA1), and menthol (TRPM8) have shown anti-obesity effects, individually and in combination. We aimed to determine the therapeutic potential of such combination of sub-effective doses of these agents against diet-induced obesity, and explore the involved cellular processes. KEY FINDINGS: The combination of sub-effective doses of capsaicin, cinnamaldehyde and menthol induced "brite" phenotype in differentiating 3T3-L1 cells and subcutaneous white adipose tissue of HFD-fed obese mice. The intervention prevented adipose tissue hypertrophy and weight gain, enhanced the thermogenic potential, mitochondrial biogenesis and overall activation of brown adipose tissue. These changes observed in vitro as well as in vivo, were linked to increased phosphorylation of kinases, AMPK and ERK. In the liver, the combination treatment enhanced insulin sensitivity, improved gluconeogenic potential and lipolysis, prevented fatty acid accumulation and enhanced glucose utilization. SIGNIFICANCE: We report on the discovery of therapeutic potential of TRP-based dietary triagonist combination against HFD-induced abnormalities in metabolic tissues. Our findings indicate that a common central mechanism may affect multiple peripheral tissues. This study opens up avenues of development of therapeutic functional foods for obesity.
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Capsaicina , Mentol , Animais , Camundongos , Capsaicina/farmacologia , Capsaicina/metabolismo , Mentol/metabolismo , Mentol/farmacologia , Mentol/uso terapêutico , Qualidade de Vida , Dieta Hiperlipídica/efeitos adversos , Obesidade/tratamento farmacológico , Obesidade/etiologia , Obesidade/metabolismo , Tecido Adiposo Marrom/metabolismo , Fenótipo , Tecido Adiposo Branco/metabolismo , Metabolismo Energético , Camundongos Endogâmicos C57BLRESUMO
Pelizaeus-Merzbacher disease, a rare X-linked recessive disease occurring predominantly in males, is a disorder of proteolipid protein expression in myelin formation in the central nervous system. The disease is clinically manifested by neurodevelopmental delay, ataxia, hypotonia, and pendular eye movement. It is best confirmed by genetic study. A 4-year female child presented with ataxia, neuroregression, decreased scholastic performance, slurred speech, loss of bladder and bowel control, and hypotonia. MRI brain showed generalized hypomyelination and atrophy of the cerebrum and cerebellum. This case highlights that Pelizaeus-Merzbacher disease can be considered even in a female child who presented with neurodevelopmental delay and neuro regression, ataxia, and decreased scholastic performance and further confirmed by MRI showing diffuse demyelination along with cerebral and cerebellar atrophy.
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INTRODUCTION: Treatment completion is associated with a better outcome in substance use disorders. We examined the rates of treatment completion and its predictors in patients admitted to specialized addiction treatment settings over a 13-year period. METHODS: Ours was a retrospective cohort study. We included consecutive 2850 patients admitted to the inpatient treatment between January 2007 and December 2019. We divided the patients into 2 groups: completed versus premature discontinuation of treatment. The predictor variables were based on previous research, clinical experience, and availability of the digital record. RESULTS: The number of patients who completed and discontinued treatments was 1873 (72.6%) and 707 (27.4%), respectively. The inpatient treatment discontinuation rate varied widely during the study period (18% in 2007 and 41% in 2012). The average rate of treatment discontinuation was 27%. The change-point analysis showed 5 statistically significant change points in the years 2008, 2010, 2012, 2014, and 2016. Patients who were prescribed medications for alcohol and opioid dependence and those who were on opioid agonist treatment had 4.7 and 6.3 higher odds of completing inpatient treatment than those who were not on medication. Patients with physical and psychiatric comorbidities had higher odds of treatment completion. Patients with a primary diagnosis of opioid dependence had lower odds of treatment completion than those with alcohol dependence. CONCLUSIONS: The rates of discontinuation may vary with concurrent changes in the treatment policies. Awareness of the risk factors and policy measures that may improve treatment completion must aid in informed decision making.
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Alcoolismo , Transtornos Relacionados ao Uso de Opioides , Humanos , Estudos Retrospectivos , Pacientes Internados , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Alcoolismo/epidemiologia , Alcoolismo/terapia , Fatores de RiscoRESUMO
Mitochondria are critical to multiple cellular processes, from the production of adenosine triphosphate (ATP), maintenance of calcium homeostasis, synthesis of key metabolites, and production of reactive oxygen species (ROS) to maintain necrosis, apoptosis, and autophagy. Therefore, proper clearance and regulation are essential to maintain various physiological processes carried out by the cellular mechanism, including mitophagy and autophagy, by breaking down the damaged intracellular connections under the influence of various genes and proteins and protecting against various neurodegenerative diseases such as Parkinson disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD), and Huntington disease (HD). In this review, we will discuss the role of autophagy, selective macroautophagy, or mitophagy, and its role in neurodegenerative diseases along with normal physiology. In addition, this review will provide a better understanding of the pathways involved in neuron autophagy and mitophagy and how mutations affect these pathways in the various genes involved in neurodegenerative diseases. Various new findings indicate that the pathways that remove dysfunctional mitochondria are impaired in these diseases, leading to the deposition of damaged mitochondria. Apart from that, we have also discussed the therapeutic strategies targeting autophagy and mitophagy in neurodegenerative diseases. The mitophagy cycle results in the degradation of damaged mitochondria and the biogenesis of new healthy mitochondria, also highlighting different stages at which a particular neurodegenerative disease could occur.
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Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Mitofagia/fisiologia , Doenças Neurodegenerativas/metabolismo , Mitocôndrias/metabolismo , Doença de Parkinson/metabolismo , Autofagia/fisiologiaRESUMO
Background: Predicting treatment response with antidepressant is a challenging task for clinicians and researchers. An important limitation of an antidepressant trial is the increased time spent before an adequacy of trial can be decided. Quantitative Electroencephalography has shown some evidence in identifying early changes seen with antidepressants. No data has been reported from Indian population on its predictive capabilities. Aim: To examine whether early changes in frontal and prefrontal theta value in QEEG could predict antidepressant treatment response. Methods: Structured clinical assessments were conducted at baseline and after one week in a sample of treatment-seeking adults with major depressive disorder (n = 50). Patients were started on SSRI (Escitalopram, fluoxetine, paroxetine or sertraline) and followed for 8 weeks. QEEG recordings were carried out at baseline and week 1 and its parameters (relative theta power and cordance) were assessed to identify its predictive value for treatment response. Treatment response was assessed using Hamilton depression rating scale with 50% reduction after 8 weeks being considered as response. Results: Mean age of the sample was 39 ± 10 years and majority of them were females (64%). A significant reduction was found in relative frontal theta value (p = 0.021) from baseline to one week in responders. However, linear regression revealed that this change could not predict the treatment response (p = 0.37). Conclusions: QEEG changes are observed in initial phase of antidepressant treatment but these changes can't predict the treatment response.
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Plant core microbiomes consist of persistent key members that provide critical host functions, but their assemblages can be interrupted by biotic and abiotic stresses. The pathobiome is comprised of dynamic microbial interactions in response to disease status of the host. Hence, identifying variation in the core microbiome and pathobiome can significantly advance our understanding of microbial-microbial interactions and consequences for disease progression and host functions. In this study, we combined glasshouse and field studies to analyse the soil and plant rhizosphere microbiome of cotton plants (Gossypium hirsutum) in the presence of a cotton-specific fungal pathogen, Fusarium oxysporum f. sp. vasinfectum (FOV). We found that FOV directly and consistently altered the rhizosphere microbiome, but the biocontrol agents enabled microbial assemblages to resist pathogenic stress. Using co-occurrence network analysis of the core microbiome, we identified the pathobiome comprised of the pathogen and key associate phylotypes in the cotton microbiome. Isolation and application of some negatively correlated pathobiome members provided protection against plant infection. Importantly, our field survey from multiple cotton fields validated the pattern and responses of core microbiomes under FOV infection. This study advances key understanding of core microbiome responses and existence of plant pathobiomes, which provides a novel framework to better manage plant diseases in agriculture and natural settings.
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Fusarium , Microbiota , Fusarium/genética , Gossypium/microbiologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , SoloRESUMO
BACKGROUND & AIM: We examined group differences in cortical thickness and surface-parameters among age and handedness--matched persons with cannabis-induced psychosis (CIP), schizophrenia with heavy cannabis use (SZC), and healthy controls (HC). METHODS: We recruited 31 men with SZC, 28 with CIP, and 30 with HC. We used the Psychiatric Research Interview for Substance and Mental Disorders to differentiate between CIP and SZC. We processed and analyzed T1 MR images using the Surface-based Brain Morphometry (SBM) pipeline of the CAT-12 toolbox within the statistical parametric mapping. After pre-processing, volumes were segmented using surface and thickness estimation for the analysis of the region of interest. We used the projection-based thickness method to assess the cortical thickness and Desikan-Killiany atlas for cortical parcellation. RESULTS: We observed the lowest cortical thickness, depth, and gyrification in the SZC, followed by CIP and the control groups. The differences were predominantly seen in frontal cortices, with limited parietal and temporal regions involvement. After False Discovery Rate (FDR) corrections and post-hoc analysis, SZC had reduced cortical thickness than HC in the middle and inferior frontal, right entorhinal, and left postcentral regions. Cortical thickness of SZC was also significantly lower than CIP in bilateral postcentral and right middle frontal regions. We found negative correlations (after FDR corrections) between the duration of cannabis use and cortical thickness in loci of parietal and occipital cortices. CONCLUSION: Our study suggested cortical structural abnormalities in schizophrenia, in reference to healthy controls and cannabis-induced psychosis, indicating different pathophysiology of SZC and CIP.