Tecovirimat is effective against human monkeypox virus in vitro at nanomolar concentrations.

The ongoing monkeypox virus (MPXV) outbreak is the largest ever recorded outside of Africa. We isolated and sequenced a virus from the first clinical MPXV case diagnosed in France (May 2022). We report that tecovirimat (ST-246), a US Food and Drug Administration approved drug, is efficacious against this isolate in vitro at nanomolar concentrations, whereas cidofovir is only effective at micromolar concentrations. Our results support the use of tecovirimat in ongoing human clinical trials.

δEPCD: the electrophysiologic coefficient of depressiveness.

Despite research advances, recently identified biological markers for depression are either non-specific or impractical in daily clinical practice. Hence, we aim to identify a novel biomarker: δEPCD, the electrophysiologic coefficient of depressiveness. δEPCD must be sensitive and specific to the vulnerability towards depression. It should also detect the presence of a depressive clinical state and be able to quantify its severity. Moreover, it should be easily accessible and cost-effective. Accordingly, combining high-frequency heart rate variability (HF-HRV), which reflects a reduction in vagal tone, and tryptophan metabolism, which influences serotonin synthesis pathway, may have a good diagnostic and prognostic accuracy in depression. δEPCD is the multiplication of the intrinsic difference between state 0 (rest) and state 1 (exposure to stress) of HF-HRV and the plasma concentration ratio between quinolinic acid and kynurenine. δEPCD theoretically fluctuates between -1000 and 0 where being closer to 0 signifies no vulnerability to depression. Individuals with a score between -16.7 and -167 have a high vulnerability to depression. Finally, individuals with a δEPCD closer to -1000 have the most severe forms of depression. δEPCD is theoretically conceived to be easy to assess and monitor which makes it a candidate for further evaluation of reliability and validity.CLINICAL SIGNIFICANCEDepression is currently diagnosed based on emotional and behavioural symptoms; however there is currently a rising interest in the field of neurobiological markers that could improve diagnostic accuracy.Many current biological approaches are primarily based on single neurobiological markers that are either non-specific or impractical in daily clinical practice.Among other neurological effects, depression may modify the parasympathetic nervous system tone and disturb the tryptophan metabolism.The electrophysiological coefficient of depressiveness δEPCD combines heart rate variability (HRV) and tryptophan metabolism to reflect the intrinsic individual vulnerability towards depression and the inherent severity of an index depressive disorder.δEPCD is the intrinsic difference between state 0 (without stress) and state 1 (exposed to a stressful task) of the high-frequency heart rate variability multiplied by the intrinsic difference between both states, e.g. state 0 and 1, of the plasma concentration ratio of quinolinic acid over kynurenine.

Can atypical dysgeusia in depression be related to a deafferentation syndrome?

Atypical dysgeusia such as having the sensation of a sweet tooth is an uncommon clinical presentation in severe depression. First, we present the case of a 67 year-old-man admitted to the psychiatric ward for depression after a suicide attempt by drug ingestion. The patient manifested a sweet taste sensation in the upper and lower gums that increased with mood swings and notably with severe depressive symptoms. Blood tests showed an elevated serum creatinine level (115 µmol/L), a normocytic anemia (hemoglobin 6.5 mmol/L; MCV 96 fL) and a deficit in vitamin B12 (122.4 pmol/L). The patient received vitamin B12 supplementation and was treated with clomipramine, lithium, mirtazapine, modafinil, and olanzapine. He was discharged after improvement of his depressive symptoms and decrease in the sweet taste. On follow-up, the patient's dysgeusia had subsided. Second, we hypothesize that the atypical dysgeusia may have been induced by vitamin B12 deficiency and medical comorbidities, leading to deafferentation (development of erroneous mouth mucosae sensations felt by the patient). This could have been increased by depression. Dysgeusia in elederly patients with depression should be extensively investigated in order to elucidate somatic contributing factors but it may not resolve until improvement of the depressive symptoms.

Reconsidering Rigidity in the Diagnosis of Neuroleptic Malignant Syndrome: A Case Report.

Neuroleptic malignant syndrome (NMS) is a rare but potentially fatal syndrome classically encountered in patients receiving typical antipsychotic agents. However, many physicians have also reported the occurrence of NMS with atypical antipsychotics, notably with atypical presentations. In this report, we present a case in which a patient's antipsychotic regimen during a psychotic episode (which involved both typical and atypical antipsychotics) subsequently led to NMS. During his stay, the patient developed an altered level of consciousness, elevation of creatine phosphokinase, hemodynamic instability, and a fever. However, the patient did not have signs of rigidity, the cardinal sign of this syndrome. The authors concluded that patients could develop NMS without rigidity while receiving an antipsychotic. Given this presentation, the authors suggest that clinicians have a high level of suspicion for NMS to avoid misdiagnosis and subsequent adverse consequences. Hence, clinicians must be vigilant about atypical presentations of NMS without rigidity.

Trauma exposure and PTSD prevalence among Yazidi, Christian and Muslim asylum seekers and refugees displaced to Iraqi Kurdistan.

BACKGROUND: There is unreliable, and negligible information on the mental health and trauma-exposure of asylum-seekers and displaced refugees in the Iraqi Kurdistan region. OBJECTIVES: To evaluate how responsible the ethno-religious origins are, for the prevalence of trauma exposure and post-traumatic stress disorder (PTSD) in displaced Iraqi asylum-seekers and refugees residing in the Iraqi Kurdistan region. METHODS: Structured interviews with a cross-sectional sample of 150 individuals, comprised of three self-identified ethno-religious groups (50 participants in each): Christians, Muslims, and Yazidis. RESULTS: 100% prevalence of trauma exposure and 48.7% of current PTSD among refugees, 70% PTSD rate of Yazidi participants, which is significantly higher (p < 0.01) compared to 44% of Muslim participants and 32% of Christian participants. These findings were corroborated using the self-rated PTSD, DSM-5 Checklist, with more severe PTSD symptom scores (p < 0.001) obtained among Yazidis (43.1; 19.7), compared to Muslims (31.3; 20.1) and Christians (29.3; 17.8). Self-rated depressive symptoms (Patient Health Questionnaire-9) were also higher (p < 0.007) among Yazidis (12.3; 8.2) and Muslims (11.7; 5.9), compared to Christians (8.1; 7).

Characterising the inhibitory actions of ceramide upon insulin signaling in different skeletal muscle cell models: a mechanistic insight.

Ceramides are known to promote insulin resistance in a number of metabolically important tissues including skeletal muscle, the predominant site of insulin-stimulated glucose disposal. Depending on cell type, these lipid intermediates have been shown to inhibit protein kinase B (PKB/Akt), a key mediator of the metabolic actions of insulin, via two distinct pathways: one involving the action of atypical protein kinase C (aPKC) isoforms, and the second dependent on protein phosphatase-2A (PP2A). The main aim of this study was to explore the mechanisms by which ceramide inhibits PKB/Akt in three different skeletal muscle-derived cell culture models; rat L6 myotubes, mouse C2C12 myotubes and primary human skeletal muscle cells. Our findings indicate that the mechanism by which ceramide acts to repress PKB/Akt is related to the myocellular abundance of caveolin-enriched domains (CEM) present at the plasma membrane. Here, we show that ceramide-enriched-CEMs are markedly more abundant in L6 myotubes compared to C2C12 myotubes, consistent with their previously reported role in coordinating aPKC-directed repression of PKB/Akt in L6 muscle cells. In contrast, a PP2A-dependent pathway predominantly mediates ceramide-induced inhibition of PKB/Akt in C2C12 myotubes. In addition, we demonstrate for the first time that ceramide engages an aPKC-dependent pathway to suppress insulin-induced PKB/Akt activation in palmitate-treated cultured human muscle cells as well as in muscle cells from diabetic patients. Collectively, this work identifies key mechanistic differences, which may be linked to variations in plasma membrane composition, underlying the insulin-desensitising effects of ceramide in different skeletal muscle cell models that are extensively used in signal transduction and metabolic studies.