RESUMEN

Clozapine-induced myocarditis (CIM) is among the most important adverse events limiting the use of clozapine as the most effective treatment for schizophrenia. CIM necessitates the immediate termination of clozapine, often resulting in its permanent discontinuation with considerable detrimental effects on patients' psychopathology and long-term outcome. Consequently, a clozapine re-challenge after CIM is increasingly regarded as a viable alternative, with published reports indicating a success rate of approximately 60%. However, published cases of re-challenges after CIM remain limited. Here, we provide a narrative review of the current state of research regarding the epidemiology, pathophysiology, risk factors, diagnosis and clinical management of CIM as well as a synthesis of current recommendations for re-challenging patients after CIM. This includes a step-by-step guide for this crucial procedure based on the current evidence regarding the pathophysiology and risk factors for CIM. Slow dose titration regimes and addressing risk factors including concomitant valproate and olanzapine are crucial both to prevent CIM and to ensure a safe and successful re-challenge. Furthermore, we discuss the utility of C-reactive protein, troponin, N-terminal-pro hormone and brain natriuretic peptide, therapeutic drug-monitoring and cardiac magnetic resonance imaging for CIM screening and diagnosis as well as for post-CIM re-challenges.

Asunto(s)

RESUMEN

In the last two decades, there has been a growing body of research that identified sex-related differences in attention-deficit hyperactivity disorder (ADHD). Our objective was to quantify whether these sex differences are based on altered functional brain connectivity profiles. In addition, we investigated whether the presence of comorbid disorders, including depression, substance use disorder (SUD) and overweight, influenced these sex differences. A seed-based connectivity analysis of the external globus pallidus (GPe), an important inhibitory relay hub of the fronto-thalamo-striatal-loop, was performed. In a first step, we searched for sex-related differences in ADHD patients (N = 137) and separately in healthy controls (HC) (N = 45), after that, we compared an equal group of HC and ADHD patients to compare sex-related differences in ADHD patients and HC. In a second step, we studied whether the neural basis of comorbidity patterns is different between male and female patients. We observed that male ADHD patients demonstrated a decrease in functional connectivity (FC) from the GPe to the left middle temporal gyrus compared to female ADHD patients. Moreover, within the full ADHD group (N = 137), there was a lower FC in male patients from GPe to the right frontal pole/middle frontal gyrus compared to female patients. Male ADHD patients with depression demonstrated decreased FC from the GPe to parts of the occipital cortex compared to female ADHD patients with depression. No such effect was demonstrated for overweight or SUD. The current study reveals different FC profiles in males and females with ADHD, which are centered around altered connectivity with the GPe. An improved understanding of sex-differences in ADHD, and the role of comorbid disorders, therein can result in improved diagnostic and therapeutic opportunities for ADHD patients.

RESUMEN

Bioremediation of fuel-contaminated soils largely depends on microbial activities, which might be stimulated using (in)organic amendments. Attenuation of a diesel-biodiesel blend (B12) was investigated in microcosms during 93 days. Soil was spiked with B12 (5%, m m-1) and, in addition to contaminated Controls (unamended), soils received compost (COB), soybean hulls (SHB), or NPK fertilizer (IB) to reach a ~20:1 carbon-to-nitrogen (C:N) ratio regarding B12-carbon content. Effects of treatments on B12 attenuation, soil respiration, heterotrophic and B12-utilizing bacteria, pH, organic-C, nitrogen contents, and phytotoxicity, were evaluated. After 20 days, diesel range organics analysis indicated 58, 48, 45, and 43% attenuation in Controls, SHB, IB, and COB, respectively. Final dissipation reached 90, 86, 72, and 60% in Controls, COB, IB, and SHB. Compost and soybean hulls appeared as preferential substrates for microorganisms. Although microbial activity (soil respiration) was 39 and 22% higher than Controls in COB and SHB, amendments postponed attenuation. Amendments transiently affected bacterial numbers as compared to Controls; however, these effects were not related to attenuation levels. pH of the contaminated soils (~7.0) dropped to 6.1 in IB, whereas pH values were between 6.7 and 7.6 in other treatments. Organic-N and Kjeldahl-N decreased during incubations, indicating net N mineralization and subsequent nitrification, although N losses could occur. Organic-C, initially higher in SHB and COB, decreased in all treatments; however, more prominent losses in COB and SHB suggest amendments were preferentially used by microorganisms. Phytotoxicity was improved in Controls; however, it was not associated with attenuation levels in amended treatments, possibly owing to formation of toxic products and B12 sorption/desorption. In IB, decreased microbial activity, delayed attenuation, and remarkable phytotoxicity were due to excessive fertilization. Therefore, intrinsic soil conditions were adequate for B12 attenuation, without the need for nutritional inputs. Results also demonstrate that toxicity bioindicators are relevant to monitor remediation.

Asunto(s)