Cardiovascular variability as a function of sleep–wake behaviour in narcolepsy with cataplexy

Hypocretin/orexin signalling varies among sleep–wake behaviours, impacts upon cardiovascular autonomic control and is impaired in patients with narcolepsy with cataplexy (NC). However, evidence concerning disturbed cardiovascular autonomic control in NC patients is contrasting, and limited mainly to waking behaviour. We thus investigated whether control of cardiovascular variability is altered in NC patients during wakefulness preceding sleep, light (1–2) and deep (3–4) stages of non‐rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep. Polysomnographic recordings and finger blood pressure measurements were performed on nine drug‐free male NC patients and nine matched healthy control subjects during spontaneous sleep–wake behaviour in a standardized laboratory environment. Indices of autonomic function were computed based on spontaneous fluctuations of systolic blood pressure (SBP) and heart period (HP). During wakefulness before sleep, NC patients showed significant decreases in indices of vagal HP modulation, cardiac baroreflex sensitivity and amplitude of central autonomic (feed‐forward) cardiac control compared with control subjects. During NREM sleep, the negative correlation between HP and subsequent SBP values was greater in NC patients than in control subjects, suggesting a greater contribution of central autonomic commands to cardiac control. Collectively, these results provide preliminary evidence that autonomic control of cardiac variability by baroreflex and central autonomic (feed‐forward) mechanisms is altered in NC patients during spontaneous sleep–wake behaviour, and particularly during wakefulness before sleep.     

Photoparoxysmal response in ADCK3 autosomal recessive ataxia: a case report and literature review

Mutations in AarF domain‐containing kinase 3 (ADCK3) are responsible for the most frequent form of hereditary coenzyme Q10 (CoQ10) deficiency (Q10 deficiency‐4), which is mainly associated with autosomal recessive cerebellar ataxia type 2 (ARCA2). Clinical presentation is characterized by a variable degree of cerebellar atrophy and a broad spectrum of associated symptoms, including muscular involvement, movement disorders, neurosensory loss, cognitive impairment, psychiatric symptoms and epilepsy. In this report, we describe, for the first time, a case of photoparoxysmal response in a female patient with a mutation in ADCK3. Disease onset occurred in early childhood with gait ataxia, and mild‐to‐moderate degeneration. Seizures appeared at eight years and six months, occurring only during sleep. Photoparoxysmal response was observed at 14 years, almost concomitant with the genetic diagnosis (c.901C>T;c.589‐3C>G) and the start of CoQ10 oral supplementation. A year later, disease progression slowed down, and photosensitivity was attenuated. A review of the literature is provided focusing on epileptic features of ADCK3‐related disease as well as the physiopathology of photoparoxysmal response and supposed cerebellar involvement in photosensitivity. Moreover, the potential role of CoQ10 oral supplementation is discussed. Prospective studies on larger populations are needed to further understand these data.     

Flow cytometry data mining by cytoChain identifies determinants of exhaustion and stemness in TCR-engineered T cells

The phenotype of infused cells is a major determinant of Adoptive T-cell therapy (ACT) efficacy. Yet, the difficulty in deciphering multiparametric cytometry data limited the fine characterization of cellular products. To allow the analysis of dynamic and complex flow cytometry samples, we developed cytoChain, a novel dataset mining tool and a new analytical workflow. CytoChain was challenged to compare state-of-the-art and innovative culture conditions to generate stem-like memory cells (T_SCM) suitable for ACT. Noticeably, the combination of IL-7/15 and superoxides scavenging sustained the emergence of a previously unidentified nonexhausted Fit-T_SCM signature, overlooked by manual gating and endowed with superior expansion potential. CytoChain proficiently traced back this population in independent datasets, and in T-cell receptor engineered lymphocytes. CytoChain flexibility and function were then further validated on a published dataset from circulating T cells in COVID-19 patients. Collectively, our results support the use of cytoChain to identify novel, functionally critical immunophenotypes for ACT and patients immunomonitoring.     

Prognostic value of the PIK3CA,AKT, and PTEN mutations in oral squamous cell carcinoma: literature review

Over 260,000 (2013) new oral squamous cell carcinoma (OSCC) cases are reported annually worldwide. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new molecular markers may be of use in prevention, prognosis, and choice of an appropriate therapy. The intracellular molecular signalling pathway of phosphatidyl-inositol-3-kinase is involved in the process of cell growth, differentiation, migration, and survival. The main components of this pathway: PIK3CA (phosphatidylinositol-4,5-bisphosphate-3-kinase catalytic subunit α), PTEN (phosphatase and tensin homologue deleted on chromosome 10), and AKT (serine-threonine kinase) are potential objects of research when introducing new therapeutic agents. The aim of this paper is to evaluate the PIK3CA, PTEN, and AKT gene mutations as prognostic factors in OSCC and to describe their role in aggressive disease progression. This is crucial for oral cancer biology understanding and for indicating which direction new clinical treatments should take.     

Traces under nails in clinical forensic medicine: not just DNA

International Journal of Legal Medicine - When dealing with complex crimes such as rape and assault, every trace takes on an essential role. The hands are often the only means of defence and...     

Atraumatic Pulsatile Leukocyte Circulation for Long‐Term In Vitro Dynamic Culture and Adhesion Assays

Low flow rate pumping of cell suspensions finds current applications in bioreactors for short‐term dynamic cell culture and adhesion assays. The aim of this study was to develop an atraumatic pump and hemodynamically adapted test circuit to allow operating periods of at least several hours. A computer‐controlled mini‐pump (MP) was constructed based on non‐occlusive local compression of an elastic tube with commercial bi‐leaflet valves directing the pulsatile flow into a compliant circuit. Cell damage and activation in the system were tested with whole blood in comparison with a set with a conventional peristaltic pump (PP). Activation of circulating THP‐1 monocytes was tested by measuring the expression of CD54 (ICAM‐1). Additionally, monocyte‐endothelial interactions were monitored using a parallel‐plate flow chamber with an artificial stenosis. The system required a priming volume of only 20 mL, delivering a peak pulsatile flow of up to 35 mL/min. After 8 h, blood hemolysis was significantly lower for MP with 11 ± 3 mg/dL compared with PP with 100 ± 16 mg/dL. CD142 (tissue factor) expression on blood monocytes was 50% lower for MP. With MP, THP‐1 cells could be pumped for extended periods (17 h), with no enhanced expression of CD54 permitting the long‐term co‐culture of THP‐1 with endothelial cells and the analysis of flow pattern effects on cell adhesion. A low‐damage assay setup was developed, which allows the pulsatile flow of THP‐1 cells and investigation of their interaction with other cells or surfaces for extended periods of time.     

Graft rinse prior to reperfusion in liver transplantation: literature review and online survey within the Eurotransplant community

Graft rinse prior reperfusion in liver transplantation (LT) is believed to reduce the incidence of postreperfusion syndrome and improve clinical outcome. A MEDLINE search was performed to obtain a comprehensive review of the published literature dealing with graft rinse in LT. Moreover, all thirty‐four LT centers in the Eurotransplant (ET) region were invited to participate in an online survey to whether or not graft rinse is performed and whether further research in the field is needed. Seventeen reports have been found to investigate graft rinse protocols in 1894 LT recipients. Eighteen of the thirty centers that participated in the online survey performed graft rinse prior reperfusion in LT. The most commonly used rinse solution was albumin. Nineteen centers stated interest in participating in a multicenter RCT in the field. The published literature does not provide concluding appraisal of the benefit of graft rinse in LT. Graft rinse protocols are not standardized and are based on personal experience. Appropriately designed clinical trials addressing the topic are demanded. The online survey appears to be a helpful tool for the evaluation of clinical practice and future research topics in the transplant community.