Bipolar disorder (BD) is a severe and common psychiatric disorder. BD pathogenesis, clinical manifestations and relapses are associated with numerous circadian rhythm abnormalities. Lithium (Li) is ...the first-line treatment in BD, and its therapeutic action has been related to its ability to alter circadian rhythms. We systematically searched the PubMed database until January 2016, aiming to critically examine published studies investigating direct and indirect effects of Li on circadian rhythms. The results, from the 95 retained studies, indicated that Li: acts directly on the molecular clocks; delays the phase of sleep-wakefulness rhythms and the peak elevation of diurnal cycle body temperature; reduces the amplitude and shortens the duration of activity rhythms and lengthens free-running rhythms. Chronic Li treatment stabilizes free-running activity rhythms, by improving day-to-day rhythmicity of the activity, with effects that appear to be dose related. Pharmacogenetics demonstrate several associations of Li's response with circadian genes (NR1D1, GSK3β, CRY1, ARNTL, TIM, PER2). Finally, Li acts on the retinal-hypothalamic pineal pathway, influencing light sensitivity and melatonin secretion. Li is a highly investigated chronobiologic agent, and although its chronobiological effects are not completely understood, it seems highly likely that they constitute an inherent component of its therapeutic action in the treatment of mood disorders.
Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is ...popularly known as "erva-cidreira" or "melissa", it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance.
Triple-negative breast cancer (TNBC) is a rare cancer, characterized by high metastatic potential and poor prognosis, and has limited treatment options. The current standard of care in nonmetastatic ...settings is neoadjuvant chemotherapy (NACT), but treatment efficacy varies substantially across patients. This heterogeneity is still poorly understood, partly due to the paucity of curated TNBC data. Here we investigate the use of machine learning (ML) leveraging whole-slide images and clinical information to predict, at diagnosis, the histological response to NACT for early TNBC women patients. To overcome the biases of small-scale studies while respecting data privacy, we conducted a multicentric TNBC study using federated learning, in which patient data remain secured behind hospitals' firewalls. We show that local ML models relying on whole-slide images can predict response to NACT but that collaborative training of ML models further improves performance, on par with the best current approaches in which ML models are trained using time-consuming expert annotations. Our ML model is interpretable and is sensitive to specific histological patterns. This proof of concept study, in which federated learning is applied to real-world datasets, paves the way for future biomarker discovery using unprecedentedly large datasets.
How Can Digital Mental Health Enhance Psychiatry? Stern, Emilie; MICOULAUD FRANCHI, Jean-Arthur; Dumas, Guillaume ...
The Neuroscientist,
12/2023, Letnik:
29, Številka:
6
Book Review, Journal Article
Recenzirano
The use of digital technologies is constantly growing around the world. The wider-spread adoption of digital technologies and solutions in the daily clinical practice in psychiatry seems to be a ...question of when, not if. We propose a synthesis of the scientific literature on digital technologies in psychiatry and discuss the main aspects of its possible uses and interests in psychiatry according to three domains of influence that appeared to us: 1) assist and improve current care: digital psychiatry allows for more people to have access to care by simply being more accessible but also by being less stigmatized and more convenient; 2) develop new treatments: digital psychiatry allows for new treatments to be distributed via apps, and practical guidelines can reduce ethical challenges and increase the efficacy of digital tools; and 3) produce scientific and medical knowledge: digital technologies offer larger and more objective data collection, allowing for more detection and prevention of symptoms. Finally, ethical and efficacy issues remain, and some guidelines have been put forth on how to safely use these solutions and prepare for the future.
We examine whether the lithium response is associated with changes in the expression of core clock genes.
The effect of a therapeutic concentration of lithium (1 mM) on the expression levels of 17 ...circadian genes was examined in lymphoblastoid cell lines (LCLs) derived from two well-characterized groups of bipolar disorder patients, defined as lithium non-responders (NR, n = 20) or excellent responders (ER, n = 16). Quantitative real-time PCR (qRT-PCR) was conducted at 2, 4 and 8 days (d2, d4 and d8) with and without lithium exposure.
At d2, in ER only, BHLHE41, RORA, PER1, ARNTL, CRY2, BHLHE40 and CSNK1D were upregulated, whereas NR1D1 was downregulated. At d4, in ER only, CRY1 was downregulated. At d8, in NR only, GSK3β was upregulated and DBP, TIMELESS and CRY1 were downregulated. Significant Group × Lithium interactions existed for NR1D1 at d2 (P = 0.02), and CRY1 at d4 (P = 0.02). Longitudinal analyses showed differential temporal evolutions between NR and ER (significant Time × Group interaction) for PER3, NR1D1, DBP, RORA, CSNK1D and TIMELESS; and a significant Time × Lithium interaction for NR1D1. Coexpression data analyses suggested distinct groups of circadian genes concurrently modulated by lithium.
In LCLs, lithium influences expression of circadian genes with differences in amplitude and kinetics according to the patient's lithium response status.
Corilagin (β-1-O-galloyl-3,6-(R)-hexahydroxydiphenoyl-d-glucose) is a tannin isolated from Phyllanthus niruri (Euphorbiaceae). This plant is well known for their therapeutic purposes to treat several ...diseases associated with dolorous process and are used in several ethno-medicines in tropical and subtropical countries.
This study was designed to evaluate the anti-hyperalgesic activity of corilagin using chemically and thermally based nociception models in mice.
Corilagin was isolated from Phyllanthus niruri (Euphorbiaceae) by extraction and chromatographic procedures and the anti-hyperalgesic activity was evaluated by using writhing, formalin, capsaicin, glutamate and hot plate tests in mice.
Corilagin presented activity in acetic acid model with the ID50 calculated value of 6.46 (3.09–13.51) being about 20.6 fold more potent than acetylsalicylic acid. It also exhibited activity against the first phase of formalin test with ID50 value of 18.38 (15.15–22.59) μmol/kg. In the capsaicin and glutamate models, corilagin demonstrated significant activity at the 3mg/kg.
The experimental data demonstrated that corilagin exhibits anti-hyperalgesic activity that may be due to interaction with the glutamatergic system.
Display omitted
Southern Brazil has the highest prevalence rate of AIDS in the country and is the only region in the Americas where HIV-1 subtype C prevails. OBJECTIVE: We evaluated the epidemiologic and clinical ...characteristics of pregnant women living with HIV/AIDS in the South region of Santa Catarina, Brazil. METHODS: All pregnant women with HIV infection attending the obstetric outpatient clinic of Criciúma, State of Santa Catarina, in 2007 (n = 46) were invited to participate. Data of 36 eligible participants were obtained through a standardized questionnaire. RESULTS: The great majority were young, with a steady partner, low family income, low education level and referring early first sexual intercourse. Many reported use of illicit non-injecting drugs (55.5%) and unprotected sex with partners that were HIV-positive (57.7%), injecting drug user (22.2%), male inmate (19.4%), truck driver (13.8%), with history of sexually transmitted disease (11.1%) or men who have sex with men (MSM) (2.8%). Most (66.7%) of the participants had their HIV diagnosis done during the pregnancy, 7 (19.4%) had a previous history of HIV mother-to-child transmission. Therapy based on highly active antiretroviral therapy (94%) was initiated at 19.3 weeks on average and 33% showed irregular antiretroviral adherence. CONCLUSION: These results confirm previous data on HIV epidemiology in Brazil and suggest that the women partners' sexual behavior and unprotected sexual intercourse are important aspects of HIV epidemic. Additional efforts in education, prophylaxis and medication adherence are needed.
Southern Brazil has the highest prevalence rate of AIDS in the country and is the only region in the Americas where HIV-1 subtype C prevails.
We evaluated the epidemiologic and clinical ...characteristics of pregnant women living with HIV/AIDS in the South region of Santa Catarina, Brazil.
All pregnant women with HIV infection attending the obstetric outpatient clinic of Criciúma, State of Santa Catarina, in 2007 (n=46) were invited to participate. Data of 36 eligible participants were obtained through a standardized questionnaire.
The great majority were young, with a steady partner, low family income, low education level and referring early first sexual intercourse. Many reported use of illicit non-injecting drugs (55.5%) and unprotected sex with partners that were HIV-positive (57.7%), injecting drug user (22.2%), male inmate (19.4%), truck driver (13.8%), with history of sexually transmitted disease (11.1%) or men who have sex with men (MSM) (2.8%). Most (66.7%) of the participants had their HIV diagnosis done during the pregnancy, 7 (19.4%) had a previous history of HIV mother-to-child transmission. Therapy based on highly active antiretroviral therapy (94%) was initiated at 19.3 weeks on average and 33% showed irregular antiretroviral adherence.
These results confirm previous data on HIV epidemiology in Brazil and suggest that the women partners’ sexual behavior and unprotected sexual intercourse are important aspects of HIV epidemic. Additional efforts in education, prophylaxis and medication adherence are needed.
Abstract Previous association studies have shown mixed results between glutamic acid decarboxylase like-1 (GADL1) gene polymorphism and prophylactic lithium response in bipolar disorder (BD) ...patients. In the present study, GADL1 gene expression was investigated in regard to lithium response, using Alda scale, in lymphoblastoid cells (LCLs) of 36 Caucasian BD patients. No difference in GADL1 expression was observed among LCLs from excellent-responders, non-responders or controls. Furthermore, lithium did not induce significant changes in GADL1 expression levels after 4 or 8 days. These results did not support an association of GADL1 expression in the determination of a lithium response in BD patients.
Lithium is the leading mood stabiliser for maintenance treatment in bipolar disorder (BD). However, response to lithium is heterogeneous with more than 60% of patients experiencing partial or no ...response.
and
molecular studies have reported the implication of kinases in the pathophysiology of BD.
Since kinases are putative targets for lithium therapeutic action, we conducted the first pilot study using kinase array technology to evaluate the global serine/threonine kinases (STK) profiles in cell lines from BD I subtype patients classified as lithium excellent-responders (ER) and non-responder (NR) to lithium treatment.
We found significant differences in the basal STK profiles between ER and NR to lithium. We also tested lithium influence on the global STK profile and found no significant difference between ER vs NR cell lines.
The results obtained in this exploratory study suggest that multiplex kinase activity profiling could provide a complementary approach in the study of biomarkers of therapeutic response in BD.
PDF
