Pericardial and Pleural Effusions in Non-ICU Hospitalized Patients with COVID-19-A Retrospective Single-Center Study.

Background: Pericardial and pleural effusions are two complications recently described in patients hospitalized with COVID-19 infections. There are several mechanisms that have been proposed and refer to SARS-CoV-2's capacity to bind to cell surfaces via various receptors and its broad tissue tropism that might cause significant complications. The aim of the present study is to evaluate the incidence of pericardial and pleural effusions during COVID-19 infection as well as to determine the risk factors associated with these complications. Methods: We conducted a retrospective single-center study that included 346 patients admitted to the National Institute of Infectious Disease "Prof. Dr. Matei Bals" (Bucharest, Romania), from 1 January to 25 May 2021, during the third wave of the pandemic. Socio-demographic and anthropometric data were collected for each patient. The patients were evaluated clinically, biologically, and radiologically within 48 h of admission. Patients were divided into 3 groups: (1) patients with pericardial effusions-18; (2) patients with pleural effusions-28; (3) patients without pericardial/pleural effusions-294. Results: After exclusion criteria were applied, 337 patients were analyzed. The median age of the participants was 58.26 ± 14.58 years. More than half of the hospitalized patients had associated respiratory failure (61.5%), of which 2.7% had a critical form of the disease and 58.8% had a severe form. The cumulative percentage for pericardial and pleural effusions for the study group was 12.8% (43 patients out of 337). The prevalence of pericardial effusion was 5.3%, twice more frequent among male respondents. Pleural effusion was identified in 8.3% patients. Most patients had unilateral effusion (17), compared to 11 patients who had bilateral involvement. Based on laboratory results, patients with pericardial and pleural effusions exhibited increased levels of C reactive protein, erythrocyte sedimentation rate, NT proBNP, and a higher value of neutrophil/lymphocyte count ratio. In contrast to patients without pleural and pericardial effusions, those with these symptoms experienced a higher frequency of severe or critical illness and longer hospital stays. Conclusions: Pericardial and pleural effusions can complicate COVID-19 infections. In our study, the prevalence of pericardial and pleural effusions in hospitalized patients was low, being associated with the same comorbidities and a number of clinical and biological parameters.

Update on Kaposi sarcoma-associated herpesvirus (KSHV or HHV8) - review.

Human herpesvirus 8 (HHV8), also known as Kaposi sarcoma-associated herpesvirus (KSHV), is one of the few pathogens recognized as direct carcinogen, being involved in the pathogenesis of Kaposi sarcoma, primary effusion lymphoma and multicentric Castleman disease. KSHV is a relatively recently discovered virus, with still limited possibilities for diagnosis and treatment. Therefore, ongoing studies are trying to answer the main issues related to the management of KSHV infection and its associated diseases. This review updates the current knowledge of the KSHV infection, discussing aspects related to epidemiology, virological features, clinical manifestations, diagnosis and treatment.

The Drosophila caspases Strica and Dronc function redundantly in programmed cell death during oogenesis.

Programmed cell death (PCD) in the Drosophila ovary occurs either during mid-oogenesis, resulting in degeneration of the entire egg chamber or during late oogenesis, to facilitate the development of the oocyte. PCD during oogenesis is regulated by mechanisms different from those that control cell death in other Drosophila tissues. We have analyzed the role of caspases in PCD of the female germline by examining caspase mutants and overexpressing caspase inhibitors. Imprecise P-element excision was used to generate mutants of the initiator caspase strica. While null mutants of strica or another initiator caspase, dronc, display no ovary phenotype, we find that strica exhibits redundancy with dronc, during both mid- and late oogenesis. Ovaries of double mutants contain defective mid-stage egg chambers similar to those reported previously in dcp-1 mutants, and mature egg chambers with persisting nurse cell nuclei. In addition, the effector caspases drice and dcp-1 also display redundant functions during late oogenesis, resulting in persisting nurse cell nuclei. These findings indicate that caspases are required for nurse cell death during mid-oogenesis, and participate in developmental nurse cell death during late oogenesis. This reveals a novel pathway of cell death in the ovary that utilizes strica, dronc, dcp-1 and drice, and importantly illustrates strong redundancy among the caspases.

The Importance of Haemogram Parameters in the Diagnosis and Prognosis of Septic Patients.

Sepsis represents a severe pathology that requires both rapid and precise positive and differential diagnosis to identify patients who need immediate antimicrobial therapy. Monitoring septic patients' outcome leads to prolonged hospitalisation and antibacterial therapy, often accompanied by substantial side effects, complications and a high mortality risk. Septic patients present with complex pathophysiological and immunological disorders and with a predominance of pro-inflammatory or anti-inflammatory mediators which are heterogeneous with respect to the infectious focus, the aetiology of sepsis or patients' immune status or comorbidities. Previous studies performed have analysed inflammatory biomarkers, but a test or combinations of tests that can quickly and precisely establish a diagnosis or prognosis of septic patients has yet to be discovered. Recent research has focused on re-analysing older accessible parameters found in the complete blood count to determine the sensitivity, specificity, positive and negative predictive values for the diagnosis and prognosis of sepsis. The neutrophil/lymphocyte count ratio (NLCR), mean platelet volume (MPV) and red blood cells distribution width (RDW) are haemogram indicators which have been evaluated and which are of proven use in septic patients' management.

ayk1, a novel mammalian gene related to Drosophila aurora centrosome separation kinase, is specifically expressed during meiosis.

A novel murine gene, designated ayk1, which encodes a putative serine/threonine kinase has been cloned and characterized. The predicted catalytic domain of the protein is highly similar to that of Drosophila aurora (62.9% identity), and to that of Saccharomyces Ipl1 (49.4% identity). All three proteins also have very basic calculated isoelectric points (higher than 10). aurora has been recently shown to be crucial for centrosome separation and chromosome segregation, while Ipl1 is essential for yeast viability and accurate chromosome segregation. The results of Northern analysis and in situ RNA localization support a similar role for ayk1. The gene is specifically expressed in meiotically active cells, and during spermatogenesis, ayk1 transcripts accumulate just before the first meiotic division. Much lower levels are found in mitotically active cells. We propose that Ayk1, aurora and Ipl1 belong to a distinct new subfamily of kinases. These results suggest that the pathways controlling chromosome segregation are evolutionary conserved, and that similar control mechanisms operate in mitosis and meiosis.

Mutations in the beta-propeller domain of the Drosophila brain tumor (brat) protein induce neoplasm in the larval brain.

Inactivation of both alleles of the fruit fly D. melanogaster brain tumor (brat) gene results in the production of a tumor-like neoplasm in the larval brain, and lethality in the larval third instar and pupal stages. We cloned the brat gene from a transposon-tagged allele and identified its gene product. brat encodes for an 1037 amino acid protein with an N-terminal B-boxl zinc finger followed by a B-box2 zinc finger, a coiled-coil domain, and a C-terminal beta-propeller domain with six blades. All these motifs are known to mediate protein-protein interactions. Sequence analysis of four brat alleles revealed that all of them are mutated at the beta-propeller domain. The clustering of mutations in this domain strongly suggests that it has a crucial role in the normal function of Brat, and defines a novel protein motif involved in tumor suppression activity. The brat gene is expressed in the embryonic central and peripheral nervous systems including the embryonic brain. In third instar larva brat expression was detected in the larval central nervous system including the brain and the ventral ganglion, in two glands - the ring gland and the salivary gland, and in parts of the foregut - the gastric caecae and the proventriculus. A second brat-like gene was found in D. melanogaster, and homologs were identified in the nematode, mouse, rat, and human. Accumulated data suggests that Brat may regulate proliferation and differentiation by secretion/transport-mediated processes.

Murine NIMA-related kinases are expressed in patterns suggesting distinct functions in gametogenesis and a role in the nervous system.

NIMA protein kinase is a major regulator of progression into mitosis in Aspergillus nidulans. Dominant negative forms of NIMA protein prevent entrance into mitosis in HeLa cells, suggesting that mammals have a similar pathway. We have reported previously the isolation of a murine NIMA-related kinase, designated Nek1, and more recently several additional NIMA-related human kinases have been cloned. The existence of several mammalian NIMA-related genes raises the questions of whether the different mammalian members have redundant, overlapping or distinct functions, and whether these functions are related to the role of NIMA in controlling mitosis. To address these questions we have studied the expression patterns of the different murine nek genes. To this end, we isolated a murine nek2 cDNA and compared its patterns of expression, during both gametogenesis and embryogenesis, to those of nek1. Both genes were highly expressed in developing germ cells, albeit in distinct patterns. In both females and males, nek1 is expressed much earlier than nek2, suggesting only limited ability for functional redundancy. Surprisingly, a striking specificity of nek1 expression was found: high levels of nek1 RNA were observed in distinct regions of the nervous system, most notably in neurons of the peripheral ganglia. These patterns suggest that the different mammalian NIMA-related kinases participate in different phases of the meiotic process and may also have functions other than cell cycle control.

NIMA-related kinases: isolation and characterization of murine nek3 and nek4 cDNAs, and chromosomal localization of nek1, nek2 and nek3.

The Aspergillus NIMA kinase plays a key role in controlling entrance into mitosis, and recent evidence suggests that mammalian NIMA-related kinases perform similar functions. We report here the cloning of the mouse nek3 and nek4 genes. Mouse nek3 is probably the ortholog of the partially sequenced, human nek3, whereas murine nek4 cDNA is probably the ortholog of human STK2. Nek4 is highly conserved between mouse and human, whereas Nek3 is somewhat less conserved (96.5 and 88% identity in the kinase domains, respectively). Northern analysis shows preferential expression of nek3 in mitotically active tissue, whereas nek4 is highly abundant in the testis. Within the developing testicular germ cells, in-situ analysis demonstrated that nek1, 2 and 4 exhibit differential patterns of expression, suggesting overlapping, but non-identical functions. Linkage analysis, using the mouse recombinant inbred strain panel (BXD), was used to localize nek1, 2 and 3. nek1 was mapped between Cpe and D8Mit8 on chromosome 8 at around 32cM, nek2 was mapped to the distal region of chromosome 1, and nek3 was mapped to the most centromeric region of chromosome 8.

[Application of the Weibull function to the study of in vivo/in vitro correlation]. / Application de la fonction de Weibull à l'étude des corrélations in vivo/in vitro.

After transformation of concentration-time curves by integration, the Weibull function is calculated, producing an equation for a derived function representing the plasma (or salivary) kinetics. This model can be employed in the analysis of in vivo/in vitro correlations, since cumulated dissolution percentages can be directly expressed as Weibull functions. A method was developed for prediction of salivary kinetics from in vitro dissolution data and the in vivo kinetics of a solution of the drug. This method was applied to results obtained for slow release formulations of acetaminophen and theophylline administered by the oral route.