Pesticide water variability and prioritization: The first steps towards improving water management strategies in irrigation hydro-agriculture areas.

The presence of pesticides in aquatic ecosystems poses significant risks to non-target organisms, necessitating monitoring and environmental risk assessment. This study aimed to evaluate the dynamics and environmental risk of pesticides in a hydro-agricultural area with intensive agricultural practices, in the Mediterranean region (South of Portugal). Seasonality and location influenced pesticide numbers and concentrations, with the highest levels observed during the dry season. Triazines, phenylureas, and organophosphates were the predominant pesticide classes, with terbuthylazine, bentazone, terbutryn, diazinon, and metolachlor exhibiting the highest detection frequencies (68 % to 72 %). Notably, 44 % of the quantified pesticides are no longer authorized in Portugal, with 33 % posing a high environmental risk. Some insecticides, including imidacloprid, methiocarb, and malathion, were occasionally detected at concentrations that posed high risks to the aquatic ecosystem (RQ ≥ 1). Irgarol, an algicide used in irrigation canals, presented a high risk in 91 % of the analysed samples. The study's distribution profile of pesticides revealed a significant transportation of these compounds from reservoirs to irrigation hydrants, establishing them as a secondary source of crop and environmental contamination. Additionally, the assessment of spatial distribution and environmental risk allowed for the identification of specific pollutants in different locations, prioritizing them based on their ecotoxicological risk to aquatic ecosystems. These findings reinforce the importance of implementing management measures at the level of hydro-agricultural areas, helping to stop the cycle of pesticide contamination. Only this type of strategy will make it possible to protect water quality, biodiversity and the health of citizens, contributing to the European Union's objectives of improving the condition of freshwater bodies and promoting the sustainable use of pesticides.

Peanut (Arachis hypogaea L.) seeds and by-products in metabolic syndrome and cardiovascular disorders: A systematic review of clinical studies.

BACKGROUND: Cardiovascular disease (CVDs) is the leading cause of death worldwide. The main risk factors are hypertension, diabetes, obesity, and increased serum lipids. The peanut (Arachis hypogaea L.), also known as the groundnut, goober, pindar, or monkey nut, belongs to the Fabaceae family and is the fourth most cultivated oilseed in the world. The seeds and skin of peanuts possess a rich phytochemical profile composed of antioxidants, such as phenolic acids, stilbenes, flavonoids, and phytosterols. Peanut consumption can provide numerous health benefits, such as anti-obesity, antidiabetic, antihypertensive, and hypolipidemic effects. Accordingly, peanuts have the potential to treat CVD and counteract its risk factors. PURPOSE: This study aims to critically evaluate the effects of peanuts on metabolic syndrome (MetS) and CVD risk factors based on clinical studies. METHOD: This review includes studies indexed in MEDLINE-PubMed, COCHRANE, and EMBASE, and the Preferred Reporting Items for a Systematic Review and Meta-Analysis guidelines were adhered to. RESULTS: Nineteen studies were included and indicated that the consumption of raw peanuts or differing forms of processed foods containing peanut products and phytochemicals could improve metabolic parameters, such as glycemia, insulinemia, glycated hemoglobin, lipids, body mass index, waist circumference, atherogenic indices, and endothelial function. CONCLUSION: We propose that this legume and its products be used as a sustainable and low-cost alternative for the prevention and treatment of MetS and CVD. However, further research with larger sample sizes, longer intervention durations, and more diverse populations is needed to understand the full benefit of peanut consumption in MetS and CVD.

Case Report: In Situ and Systemic Immune Response to Mucosal Leishmaniasis in an HIV-Infected Patient.

In situ and systemic evaluations of the immune responses of HIV-infected patients to mucosal leishmaniasis have been poorly described. We describe a recently diagnosed HIV-infected patient with mucosal leishmaniasis who was characterized by a CD4 count of 85 cells/mm3 and nasal septum destruction resulting from pruritic and ulcerated nasal mucosa with crust formation and progression over 2 years. In situ and systemic immune evaluations of T cell activation, memory, and exhaustion were conducted using cytofluorometric assays, and sequencing of the Leishmania species was performed. The immune profile of HIV-infected patient with mucosal leishmaniasis shows a mixed Th1/Th2 pattern and an activated and exhausted status.

Epidemiology of measles in Angola: Results from routine surveillance from 2015 to 2021.

Background: Measles, an acute infectious disease of extremely contagious viral aetiology, has been eliminated in some parts of the world. To the best of the authors' knowledge, this is the first study on the epidemiological pattern of the measles virus in Angola, and it was carried out through a review of 7 years of observational retrospective data from the national measles laboratory surveillance programme. Methods: A retrospective study using national databases on the laboratory surveillance of measles was performed. Patients of all ages with suspected measles from all provinces of Angola were included. Serum samples were used to detect IgM-type measles-virus-specific antibodies by enzyme-linked immunosorbent assay. Findings: In total, 3690 suspected measles samples were sent to the Instituto Nacional de Investigação em Saúde. There were 962 (26.1%) laboratory-confirmed cases, and the most affected age group was children aged 1-4 years. The highest incidence rate per 100,000 population was found in Benguela (17.9%), followed by Huambo (16.7%) and Cuanza Sul (13.6%). Of the study years, the incidence rate per 1,000,000 population was highest in 2020 (11.9%). The most common complication was diarrhoea (n=406, 42.2%). Of the confirmed cases, 209 (21.7%) were vaccinated, 633 (65.8%) were unvaccinated, and 120 (12.5%) had unknown vaccination status. For all study years, vaccination coverage was <70%. Interpretation: Measles continues to be a serious problem in Angola, and more efforts are needed to increase measles surveillance and achieve a high percentage of vaccination coverage.

Anti-Inflammatory, Antioxidant, and Other Health Effects of Dragon Fruit and Potential Delivery Systems for Its Bioactive Compounds.

Dragon fruit (Hylocereus genus) has the potential for the prevention of diseases associated with inflammatory and oxidative processes. We aimed to comprehensively review dragon fruit health effects, economic importance, and possible use in delivery systems. Pubmed, Embase, and Google Scholar were searched, and PRISMA (Preferred Reporting Items for a Systematic Review and Meta-Analysis) guidelines were followed. Studies have shown that pitaya can exert several benefits in conditions such as diabetes, dyslipidemia, metabolic syndrome, cardiovascular diseases, and cancer due to the presence of bioactive compounds that may include vitamins, potassium, betacyanin, p-coumaric acid, vanillic acid, and gallic acid. Moreover, pitaya has the potential to be used in food and nutraceutical products as functional ingredients, natural colorants, ecologically correct and active packaging, edible films, preparation of photoprotective products, and additives. Besides the importance of dragon fruit as a source of bioactive compounds, the bioavailability is low. The development of delivery systems such as gold nanoparticles with these compounds can be an alternative to reach target tissues.

Attention-deficit/hyperactivity disorder and other neurodevelopmental disorders in offspring of parents with depression and bipolar disorder.

BACKGROUND: Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls. METHOD: We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder. RESULTS: Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23-4.47, p = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03-3.39, p = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring. CONCLUSIONS: Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.

Pesticides in sediments of the Ebro River Delta cultivated area (NE Spain): Occurrence and risk assessment for aquatic organisms.

Intense agricultural activities are performed in the Ebro River Delta (NE Spain) with extensive use of pesticides. Medium to highly polar pesticides have not been studied intensively in sediments despite its larger use in the recent years. This work aimed at assessing the occurrence of 69 pesticides, including medium to highly polar compounds, in sediments collected from drainage and irrigation channels of the Ebro River Delta during the main rice growing season. In addition, an environmental risk assessment was performed to evaluate the potential adverse effects to sediment-dwelling organisms with the risk quotient approach. A total of 24 pesticides were detected in sediments with bentazone and cypermethrin exhibiting high detection frequencies (79%) as well as high mean concentration levels (61.9 and 81.8 ng g-1 dw, respectively). Overall, the Alfacs bay, in the South of the delta, presented higher pesticide contamination than the Fangar bay, in the North. A similar pesticide distribution profile was observed in both bays, with oxadiazoles, organochlorines, pyrethroids, benzothiazinones and organophosphates as major, predominant classes. The presence of oxadiazon, pendimethalin and thifensulfuron methyl in the sediments may pose a moderate risk to sediment-dwelling organisms while bentazone, chlorpyrifos, and cypermethrin exhibited a potential high risk. Thus, the importance of the inclusion of medium to highly polar pesticides in the analysis of sediments is emphasized since some polar pesticides such as bentazone, imidacloprid, and thifensulfuron-methyl have been detected at concentrations that may pose a risk to aquatic organisms. Moreover, the co-occurrence of pesticides may potentially pose a high risk to sediment-dwelling organisms in 13 out of the 14 investigated locations. Finally, it could be concluded that the risk derived from the presence of pesticides in sediments must be assessed since some pesticides not detected at concerning levels in water, may pose a moderate/high risk in the sediments.

Evaluation of a Vitamin D Screening and Treatment Protocol Using a Seasonal Calculator in Athletes.

ABSTRACT: Vitamin D is important in musculoskeletal health, and low serum vitamin D concentration is common in athletes. This study implemented a vitamin D screening and supplementation protocol in a cohort of National Collegiate Athletic Association Division I athletes using summer 25-hydroxyvitamin D concentration and a seasonal variation calculator to achieve sufficient vitamin D concentration year-round. After implementation of the Vitamin D Protocol, there was a nonsignificant difference in athletes with sufficient winter vitamin D concentrations (72.6%) compared with summer vitamin D concentrations (66.1%) (P = 0.40). The Seasonal Variation Calculator predicted winter vitamin D concentrations (8 ± 18 ng·mL-1) higher than actual winter vitamin D concentrations (P < 0.01). While most athletes (78%) believed vitamin D was important for athletic performance, athlete compliance to the Vitamin D Protocol was inconsistent. In the future, adjustment of vitamin D screening and supplementation protocols may help athletes achieve sufficient vitamin D status year-round.

Urinary 6-sulfatoxymelatonin Levels and Prostate Cancer Risk among Men in the Multiethnic Cohort.

BACKGROUND: The circadian hormone melatonin has anticancer properties, and prior studies suggest a positive association between low melatonin and prostate cancer risk. The purpose of this study was to examine urinary melatonin levels and prostate cancer in a racially/ethnically diverse cohort. METHODS: We conducted a nested case-control study, including 1,263 prostate cancer cases and 2,346 controls, sampled from participants in the Multiethnic Cohort Study with prediagnostic urine samples assayed for 6-sulfatoxymelatonin, the primary melatonin metabolite. Conditional logistic regression was used to examine the association between melatonin levels and the development of prostate cancer outcomes (all incident cases, advanced, lethal, high-grade, and aggressive), overall and by race/ethnicity. RESULTS: Among 1,263 cases, 135 were advanced stage, 101 were lethal cases, and 282 were high-grade disease. Median melatonin levels were similar in controls [17.12 ng/mL; interquartile range (IQR), 19.78] and cases (17.93 ng/mL; IQR, 19.76), and we found no significant association between urinary melatonin levels and prostate cancer risk overall or in any clinical or racial subgroup. CONCLUSIONS: In this diverse cohort, there was no significant association between melatonin and any prostate cancer outcome, nor were there any differences by racial/ethnic group. IMPACT: These results do not support a strong association between melatonin levels and risk of prostate cancer.

Occurrence and risk assessment of pesticides in a Mediterranean Basin with strong agricultural pressure (Guadiana Basin: Southern of Portugal).

The study aimed to assess the occurrence and the environmental risk of a group of 51 selected pesticides in the Guadiana Basin (a biodiversity hotspot, in the Mediterranean). The most abundant pesticides were bentazone and 2,4-D, while terbuthylazine together with terbutryn constituted the most ubiquitous pesticides. Eighteen out of the 38 pesticides detected are no longer approved in Europe, and 5 of them are included in the list of priority substances. The risk assessment showed that azinphos ethyl, diflufenican, irganol, imidacloprid, and oxadiazon occurred occasionally, but always in concentrations above their respective ecotoxicological threshold value. Contrary, bentazone, terbuthylazine, and terbutryn presented a high risk in most of the sampled locations and periods. The site-specific risk assessment showed a spatial and temporal pattern, with a higher risk occurring mainly in intermittent streams, in the drought period. The presence of pesticides banned from the EU market since 2009 showed the importance of improving the monitoring process, to identify the main sources of pollution and the fate of these emerging compounds. The results showed the need of implementing actions to improve the sustainable use of pesticides in agricultural areas, working with farmers and management entities to reduce the contamination of aquatic ecosystems. Transboundary water governance is also required to solve potential transboundary contamination problems.

Posttranslational modifications & lithium's therapeutic effect-Potential biomarkers for clinical responses in psychiatric & neurodegenerative disorders.

Several neurodegenerative diseases and neuropsychiatric disorders display aberrant posttranslational modifications (PTMs) of one, or many, proteins. Lithium treatment has been used for mood stabilization for many decades, and is highly effective for large subsets of patients with diverse neurological conditions. However, the differential effectiveness and mode of action are not fully understood. In recent years, studies have shown that lithium alters several protein PTMs, altering their function, and consequently neuronal physiology. The impetus for this review is to outline the links between lithium's therapeutic mode of action and PTM homeostasis. We first provide an overview of the principal PTMs affected by lithium. We then describe several neuropsychiatric disorders in which PTMs have been implicated as pathogenic. For each of these conditions, we discuss lithium's clinical use and explore the putative mechanism of how it restores PTM homeostasis, and thereby cellular physiology. Evidence suggests that determining specific PTM patterns could be a promising strategy to develop biomarkers for disease and lithium responsiveness.

Deficient LEF1 expression is associated with lithium resistance and hyperexcitability in neurons derived from bipolar disorder patients.

Bipolar disorder (BD) is a psychiatric condition characterized by depressive and manic episodes that affect 2% of the world population. The first-line long-term treatment for mood stabilization is lithium (Li). Induced pluripotent stem cell modeling of BD using hippocampal dentate gyrus-like neurons derived from Li-responsive (LR) and Li-non-responsive (NR) patients previously showed neuronal hyperexcitability. Li treatment reversed hyperexcitability only on the LR neurons. In this study we searched for specific targets of Li resistance in NR neurons and found that the activity of Wnt/ß-catenin signaling pathway was severely affected, with a significant decrease in expression of LEF1. Li targets the Wnt/ß-catenin signaling pathway by inhibiting GSK-3ß and releasing ß-catenin that forms a nuclear complex with TCF/LEF1, activating the Wnt/ß-catenin transcription program. Therefore, we propose that downregulation of LEF1 may account for Li resistance in NR neurons. Our results show that valproic acid (VPA), a drug used to treat NR patients that also acts downstream of GSK-3ß, upregulated LEF1 and Wnt/ß-catenin gene targets, increased transcriptional activity of complex ß-catenin/TCF/LEF1, and reduced excitability in NR neurons. In addition, decreasing LEF1 expression in control neurons using shLEF1 caused hyperexcitability, confirming that the impact of VPA on excitability in NR neurons was connected to changes in LEF1 and in the Wnt/ß-catenin pathway. Our results suggest that LEF1 may be a useful target for the discovery of new drugs for BD treatment.

Case Report: Severe Visceral Leishmaniasis in a Patient with HIV Coinfection Undergoing Treatment for Erythema Nodosum Leprosum.

We report a case of visceral leishmaniasis (VL)/HIV coinfection in a patient undergoing regular antiretroviral therapy and treatment with thalidomide for erythema nodosum leprosum. He presented at a health service with high fever, chills, asthenia, pale skin, lower limb edema, hepatomegaly, and splenomegaly. Visceral leishmaniasis was confirmed by direct examination, and serological and molecular tests. Serum levels of Th1/Th2 cytokines were measured. The patient began treatment with liposomal amphotericin B, with good clinical response; however, VL recurred 6 months later. Treatment was reinitiated, maintaining secondary prophylaxis with liposomal amphotericin B. The patient showed clinical improvement with important recovery of CD4+ T-lymphocyte count.

El análisis de aguas residuales con fines epidemiológicos: presente y futuro en España / Wastewater-based epidemiology: present and future in Spain

El análisis de aguas residuales con fines epidemiológicos es actualmente una herramienta fiable y complementaria a las metodologías basadas en indicadores tradicionales para el control de diferentes sustancias entre las que cabe destacar las drogas. Si bien varios países europeos la utilizan como herramienta de trabajo para la monitorización de drogas de abuso, en España su uso se limita principalmente a estudios realizados por diferentes grupos de investigación, tal y como se describe en el caso práctico puesto de ejemplo en el artículo. Sin embargo, el potencial de la metodología ha quedado evidenciado en los estudios científicos llevados a cabo tanto a nivel español como internacional y, aunque son necesarios más estudios para llegar a conocer todo su potencial, se prevé pueda ser incorporada como herramienta de trabajo complementaria a las que habitualmente se utilizan. En este sentido, la Red Española de Análisis de Aguas Residuales (ESAR-Net), creada en 2017 y formada por diferentes grupos de investigación españoles, pretende contribuir al conocimiento y aplicación de esta metodología en España a través de actividades científicas y de divulgación

Wastewater-Based Epidemiology is currently a reliable and complementary tool to methodologies based on traditional indicators for the control of various substances such as drugs. Although several European countries use it as a working tool for the monitoring of drugs of abuse, in Spain its use is mainly limited to studies carried out by different research groups, as described in the case study used as an example in the article. However, the potential of the methodology has been demonstrated in the scientific studies carried out both at the Spanish and international level and, although more studies are necessary to get to know its full potential, it is expected that it could be incorporated as a complementary work tool to those that are usually used. In this sense, the Red Española de Análisis de Aguas Residuales (ESAR-Net), created in 2017 and formed by different Spanish research groups, aims to contribute to the knowledge and application of this methodology in Spain through scientific and outreach activities

Can network analysis shed light on predictors of lithium response in bipolar I disorder?

OBJECTIVE: To undertake a large-scale clinical study of predictors of lithium (Li) response in bipolar I disorder (BD-I) and apply contemporary multivariate approaches to account for inter-relationships between putative predictors. METHODS: We used network analysis to estimate the number and strength of connections between potential predictors of good Li response (measured by a new scoring algorithm for the Retrospective Assessment of Response to Lithium Scale) in 900 individuals with BD-I recruited to the Consortium of Lithium Genetics. RESULTS: After accounting for co-associations between potential predictors, the most important factors associated with the good Li response phenotype were panic disorder, manic predominant polarity, manic first episode, age at onset between 15-32 years and family history of BD. Factors most strongly linked to poor outcome were comorbid obsessive-compulsive disorder, alcohol and/or substance misuse, and/or psychosis (symptoms or syndromes). CONCLUSIONS: Network analysis can offer important additional insights to prospective studies of predictors of Li treatment outcomes. It appears to especially help in further clarifying the role of family history of BD (i.e. its direct and indirect associations) and highlighting the positive and negative associations of different subtypes of anxiety disorders with Li response, particularly the little-known negative association between Li response and obsessive-compulsive disorder.

Cognitive-behavioral-based physical therapy to enhance return to sport after anterior cruciate ligament reconstruction: An open pilot study.

OBJECTIVES: To describe feasibility, adherence, acceptability, and outcomes of a cognitive-behavioral-based physical therapy (CBPT-ACLR) intervention for improving postoperative recovery after anterior cruciate ligament reconstruction (ACLR). DESIGN: Pilot study. SETTING: Academic medical center. PARTICIPANTS: Eight patients (mean age [SD] = 20.1 [2.6] years, 6 females) participated in a 7-session telephone-based CBPT-ACLR intervention beginning preoperatively and lasting 8 weeks after surgery. MAIN OUTCOME MEASURES: At 6 months, patients completed Knee Injury and Osteoarthritis Outcome Score (KOOS) sports/recreation and quality of life (QOL) subscales, International Knee Documentation Committee (IKDC), Tampa Scale of Kinesiophobia (TSK), Pain Catastrophizing Scale (PCS), and Knee Self-Efficacy Scale (K-SES), return to sport (Subjective Patient Outcome for Return to Sports), and satisfaction. Minimal clinically important difference (MCID) was used for meaningful change. RESULTS: Seven (88%) patients completed all sessions. Seven (88%) patients exceeded MCID on the TSK, 6 (75%) on the PCS, 5 (63%) on the KOOS sports/recreation subscale, 4 (50%) on the IKDC, and 3 (38%) on the KOOS QOL subscale. Three (38%) patients returned to their same sport at the same level of effort and performance. All patients were satisfied with their recovery. CONCLUSIONS: A CBPT-ACLR program is feasible and acceptable for addressing psychological risk factors after ACLR.

Refined diagnostic criteria for the bipolar disorders: phase two of the AREDOC project.

OBJECTIVE: As limitations exist across DSM criteria sets for defining and differentiating the bipolar disorders generally and their component bipolar I (BP-1) and bipolar II (BP-II) sub-types, we sought to generate empirically based criteria. METHOD: We formed an international Task Force (TF) comprising members with bipolar disorder expertise, and who recruited 74 patients with a TF-diagnosed bipolar I and 104 with a bipolar II condition (with patients responding to definitional queries and symptom questionnaires), while 33 unipolar depressed patients recruited by the first author also completed the symptom questionnaire. A factor analysis sought to determine granular hypo/manic constructs. RESULTS: The bipolar disorder subjects strongly affirmed a new general definition of a bipolar disorder (capturing both manic and hypomanic episodes). While DSM-5 requires impaired functioning, we established that a high percentage of individuals with a BP-I or a BP-II disorder reported improved functioning and therefore modified this criterion. Analyses identified syptoms with differential high rates in individuals with bipolar disorder and its sub-types (and thus not simply capturing happiness), while a factor analysis generated seven symptom constructs both linked with and differing from DSM-5 bipolar symptom criteria. CONCLUSION: This second-stage report details a new set of criteria for differentiating the bipolar disorders from unipolar depressive conditions, while arguing for BP-I and BP-II disorders being differentiated principally by the respective presence or absence of psychotic features. Future studies will evaluate whether further modifications are required and examine for differential treatment benefits for those with a BP-I versus a BP-II condition.

Observed psychopathology in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia.

BACKGROUND: Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state. METHODS: Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders. RESULTS: Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia. CONCLUSIONS: Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.

Prediction of lithium response using clinical data.

OBJECTIVE: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers. METHOD: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.7% responders), collected across seven sites, internationally. We trained a random forest model to classify LR-as defined by the previously validated Alda scale-against 180 clinical predictors. RESULTS: Under appropriate cross-validation procedures, LR was predictable in the pooled sample with an area under the receiver operating characteristic curve of 0.80 (95% CI 0.78-0.82) and a Cohen kappa of 0.46 (0.4-0.51). The model demonstrated a particularly low false-positive rate (specificity 0.91 [0.88-0.92]). Features related to clinical course and the absence of rapid cycling appeared consistently informative. CONCLUSION: Clinical data can inform out-of-sample LR prediction to a potentially clinically relevant degree. Despite the relevance of clinical course and the absence of rapid cycling, there was substantial between-site heterogeneity with respect to feature importance. Future work must focus on improving classification of true positives, better characterizing between- and within-site heterogeneity, and further testing such models on new external datasets.