Characterization of the viability and the function of granulocytes used for transfusion

Les granulocytes neutrophiles sont les cellules immunitaires les plus abondantes dans l'organisme. Elles constituent notre première ligne de défense contre les infections microbiennes. Les personnes neutropéniques sont à haut risque de mortalité en cas d'infections microbiennes graves. Lorsque les traitements antimicrobiens standards sont inefficaces, les patients peuvent recevoir une transfusion de concentré de granulocytes (CG) pour rétablir temporairement un nombre de neutrophiles en circulation permettant d'éradiquer l'infection. Au Canada, les CG sont préparés par Héma-Québec à partir de donneurs stimulés avec une dose de prednisone augmentant le nombre de neutrophiles en circulation. Aux États-Unis le G-CSF sert d'agent de stimulation des donneurs. Les neutrophiles sont récoltés par leucaphérèse et certifiés pour la transfusion selon le nombre de neutrophiles récoltés. Or, ce critère ne reflète pas la viabilité et l'état fonctionnel des cellules transfusées. Notre étude compare la viabilité, le phénotype et les fonctions antimicrobiennes des neutrophiles obtenus des CG dérivés de prednisone et de G-CSF. La prednisone mobilise des neutrophiles matures avec une phagocytose augmentée mais le nombre de neutrophiles est souvent proche de la limite transfusable. Le G-CSF augmente considérablement le nombre de neutrophiles récoltés, dont près de la moitié sont immatures, en plus d'abaisser la chimiotaxie et d'augmenter la production de cytokines. D'après nos résultats, la durée d'entreposage des CG est le paramètre le plus critique pour le maintien de la viabilité et des fonctions antimicrobiennes des neutrophiles, particulièrement pour ceux dérivés du G-CSF alors que la leucaphérèse a un effet négligeable sur les deux types de CG. L'amélioration des processus de fabrication, d'entreposage des CG et leur certification avec un critère fonctionnel permettra de maintenir la viabilité et les fonctions des neutrophiles et d'assurer leur efficacité in vivo.Neutrophil granulocyte are the most abundant immune cells in the organism. They constitute our first line of defence against invasive pathogens. Neutropenic patients with life-threatening infections can be transfused with granulocyte concentrates (GCs) to temporarily restore a sufficient number of circulating neutrophils to eradicate infection. In Canada, GC are prepared by Héma-Québec from donors pre-treated with a unique dose of prednisone enhancing the number of circulating neutrophils. In the U.S, G-CSF is used as mobilizing agent in the donors. Neutrophils are collected by leukapheresis and certified for transfusion according to the number of neutrophils collected. This criterion, however, does not reflect the viability and the functional capacity of the transfused cells. Our study compare the viability, the phenotype and antimicrobial functions of neutrophils from prednisone and G-CSF-derived GCs. Prednisone mobilizes mature neutrophils with enhanced phagocytosis although the number of collected neutrophils is sometimes below the required transfusion dose of 1 x10¹⁰ granulocytes per unit. G-CSF significantly increases the number of collected neutrophils, though almost half are immature, along with decreasing chemotaxis and increasing cytokine production. According to our results, storage duration is the most critical parameter for the preservation of neutrophils viability and antimicrobial functions, particularly for G-CSF-derived GC neutrophils whereas leukapheresis had negligible effect for both type of GCs. The improvement of GCs supply chain and storage as well as certification based on a functional criterion will allow to preserve the viability and effector functions of neutrophils and guaranty GCs in vivo efficacy

The accuracy of the Italian version of the Hypomania Checklist (HCL-32) for the screening of bipolar disorders and comparison with the Mood Disorder Questionnaire (MDQ) in a clinical sample

BACKGROUND: The study measured the accuracy of the Italian version of the Hypomania Checklist (HCL-32) for self-assessment as a screening instrument for bipolar disorder (BPD) in a psychiatric setting and compared results with a previous study, carried out in a comparable sample and in the same setting, using the Mood Disorder Questionnaire (MDQ). METHODS: 123 consecutive subjects attending a psychiatric division were screened for BPD using the Italian translation of the HCL-32, and diagnostically interviewed with the SCID by physicians. The sample of the previous study using the MDQ consisted of 154 subjects. RESULTS: On the basis of the SCID: 26 received a diagnosis of bipolar/schizoaffective disorder, 57 were diagnosed as having at least another psychiatric disorder in Axis-I, whilst 40 were unaffected by any type of psychiatric disorder. Comparing the bipolar with all other patients the HCL-32 showed a good accuracy: cut-off 8: sensitivity 0.92-specificity 0.48; cut-off 10: sensitivity 0.88-specificity 0.54; cut-off 12: sensitivity 0.85-specificity 0.61. The accuracy for BPD-II (10) remains good: cut-off 8: sensitivity 0.90-specificity 0.42; cut-off 10: sensitivity 0.80-specificity 0.47; cut-off 12: sensitivity 0.80-specificity 0.54. The comparison with the MDQ performance shows that both screening tools may show good results, but HCL-32 seems to be more sensitive in detecting BPD-II. CONCLUSION: Our results seem to indicate good accuracy of HCL-32 as a screening instrument for BPD in a psychiatric setting, with a low rate of false negatives, and a fairly good degree of identification of BPD-II

Defining clinical characteristics of emotion dysregulation in bipolar disorder: A systematic review and meta-analysis

Emotion dysregulation (ED) is characterized by rigid and frequent use of maladaptive emotion regulation (ER) strategies. Conceptualized as a transdiagnostic feature, ED may occur in both clinical and non-clinical populations, including people diagnosed with bipolar disorder (BD) and their first-degree relatives (FDRs), though expected to manifest with differential clinical features. To this end, we conducted a systematic review and meta-analysis of the literature comparing people with BD to healthy controls (HCs) or FDRs, from inception up to November 25, 2021, across major databases. Random-effects meta-analyses considered twenty-eight studies assessing ER/ED with a validated scale. Patients with BD differed from HCs in adopting more maladaptive ER strategies, such as rumination, risk-taking behaviors, negative focus, and less adaptive ones. Unaffected FDRs differed from people with BD, yet to a lower extent, suggesting that ED may span a continuum. ED in BD should be widely explored to better understand its course and management, with specific interventions aimed at reducing its burden on both high-risk and full-threshold populations

Lithium and bipolar depression

Kelly1 has recently disputed the recommendations of several international guidelines on the use of lithium in bipolar depression. In his scrutiny, the author points to three main errors that seem to have affected systematically ten international guidelines, namely the Woozle effect (evidence by citation), reference inflation (inappropriate citation of pivotal, generally old, studies) and belief perseverance (inability to modify evidence‐based recommendations despite the presence of contrary data). We concur with the author that the evidence supporting the effectiveness of lithium in acute bipolar depression, and to a lesser degree also in major depressive episodes, remains inadequate.2, 3 A different matter is, in our opinion, to label guidelines recommendations as inaccurate or biased, even if, as the author stated, no deceptive intentions were present

Effects of light, temperature, salinity, and maternal habitat on seed germination of aeluropus lagopoides (Poaceae): An economically important halophyte of arid Arabian deserts

In this study, salt tolerance during germination of Aeluropus lagopoides (L.) Trin. was tested using fresh seeds collected from three different maternal habitats under three thermoperiods and two light regimes. Additionally, we tested the ability of non-germinated seeds that had been exposed to different concentrations of NaCl to recover their germination in distilled water. The results showed a significant effect of seed source, temperature, and salinity, and some of their two-and three-way interactions on final germination and recovery percentage. The seeds from non-saline provenances had the highest percentages for germination (ca. 79%) under the 35/25 °C temperature regime, whereas the lowest percentages for germination (ca. 21%) was recorded for seeds from saline conditions under the 25/15 °C treatment. Additionally, percent germination was significantly lower for the seeds incubated in the saline solutions (100, 200, 400, and 600 mmol/L NaCl) and germinated under colder conditions (15/25 °C), compared with the seeds incubated in non-saline solutions (control group, 0 mmol/L NaCl) and germinated under warmer conditions (35/25 °C). The highest recovery percentage was recorded for seeds of the hyper-saline habitat incubated at 35/25 °C. Thus, seeds maintained their viability despite experiencing a range of saline conditions and were able to germinate upon the arrival of suitable conditions, which can be an adaptation to its saline arid desert habitat.Fil: Bhatt, Arvind. Botanical Garden; China. Kuwait Institute For Scientific Research; KuwaitFil: Gairola, Sanjay. Sharjah Research Academy; Emiratos Arabes UnidosFil: Carón, María Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Santo, Andrea. Università Degli Studi Di Cagliari.; ItaliaFil: Murru, Valentina. Università Degli Studi Di Cagliari.; ItaliaFil: El-Keblawy, Ali. University Of Sharjah; Emiratos Arabes UnidosFil: Mahmoud, Tamer. University Of Sharjah; Emiratos Arabes Unido

Multiple Immune-Inflammatory and Oxidative and Nitrosative Stress Pathways Explain the Frequent Presence of Depression in Multiple Sclerosis

Patients with a diagnosis of multiple sclerosis (MS) or major depressive disorder (MDD) share a wide array of biological abnormalities which are increasingly considered to play a contributory role in the pathogenesis and pathophysiology of both illnesses. Shared abnormalities include peripheral inflammation, neuroinflammation, chronic oxidative and nitrosative stress, mitochondrial dysfunction, gut dysbiosis, increased intestinal barrier permeability with bacterial translocation into the systemic circulation, neuroendocrine abnormalities and microglial pathology. Patients with MS and MDD also display a wide range of neuroimaging abnormalities and patients with MS who display symptoms of depression present with different neuroimaging profiles compared with MS patients who are depression-free. The precise details of such pathology are markedly different however. The recruitment of activated encephalitogenic Th17 T cells and subsequent bidirectional interaction leading to classically activated microglia is now considered to lie at the core of MS-specific pathology. The presence of activated microglia is common to both illnesses although the pattern of such action throughout the brain appears to be different. Upregulation of miRNAs also appears to be involved in microglial neurotoxicity and indeed T cell pathology in MS but does not appear to play a major role in MDD. It is suggested that the antidepressant lofepramine, and in particular its active metabolite desipramine, may be beneficial not only for depressive symptomatology but also for the neurological symptoms of MS. One clinical trial has been carried out thus far with, in particular, promising MRI findings

Should be a Third Dose of BNT162b2 mRNA COVID-19-Vaccine Administered in Patients with Myelofibrosis Under Ruxolitinib?

Patients with Myelobrosis (MF) are considered fragile and thus eligible in Italy for COVID-19 BNT162b2 mRNA vaccination. According to the International Prognostic Scoring System (IPSS), patients with intermediate and high MF, may receive clinical benets from ruxolitinib, the rst approved JAK1/JAK2 inhibitor. Given the potent anti-in ammatory properties of ruxolitinib against immunocompetent cells, we previously reported a lower but non-statistically absolute IgG anti-Spike humoral response in vaccinated MF patients treated with ruxolitinib. In the present report we extended the cohort of MF patients

A case control study on psychiatric disorders in Hashimoto disease and euthyroid goitre: not only depressive but also anxiety disorders are associated with thyroid autoimmunity

OBJECTIVE: To evaluate the association between mood and anxiety disorders in Hashimoto disease and Euthyroid Goitre in a case control study. METHODS: Cases included 19 subjects with Hashimoto disease in euthyroid phase, 19 subjects with euthyroid goitre, 2 control groups each of 76 subjects matched (4/1) according to age and sex drawn from the data base of a community based sample. Psychiatric diagnoses were formulated using the International Composite Diagnostic Interview Simplified, according to DSM-IV criteria. All subjects underwent a complete thyroid evaluation including physical examination, thyroid echography and measure of serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase autoantibodies (anti-TPO). Results: Subjects with Hashimoto disease showed higher frequencies of lifetime Depressive Episode (OR = 6.6, C.L. 95% 1.2–25.7), Generalized Anxiety Disorders (OR = 4,9 Cl 95% 1.5–25.4) and Social Phobia (OR = 20.0, CL 95% 2.3–153.3) whilst no differences were found between subjects with goitre and controls. CONCLUSION: The study seems to confirm that risk for depressive disorders in subjects with thyroiditis is independent of the thyroid function detected by routine tests and indicates that not only mood but also anxiety disorders may be associated with Hashimoto disease