Distribution and spatial geometry of dopamine interplexiform cells in the retina. II. External arborizations in the adult rat and monkey

The morphology and distribution of dopaminergic interplexiform cells in adult rat and monkey retinas were analyzed to determine any correlation with the function of dopamine in the outer retinal layers. The retinas were processed as whole mounts for tyrosine hydroxylase immunohistochemistry. There was a network formed by the sclerally directed processes of interplexiform cells in the inner nuclear, outer plexiform, and outer nuclear layers running throughout the retina. Their density was higher in the superior retina than in the inferior retina of the rat and was especially high in the superior temporal quadrant. The external network in this quadrant was significantly less dense in the monkey than in the rat, as are the interplexiform cells. The somata of interplexiform and other dopaminergic cells were about the same size in both rats and monkeys. Computer-assisted reconstruction of external arborizations of individual cells showed that external processes lay very close to horizontal and photoreceptor cells and also to blood capillaries. Because they were long, thin, and highly varicose; branched at right angles; and often arose from an axon hillock, the external processes were identified as axons. Therefore, we define the dopaminergic interplexiform cells as multiaxonal neurons, with at least one outwardly directed axon that reaches the outer plexiform layer. The function of the network of external processes from the interplexiform dopaminergic cells is discussed in terms of modulating the release of dopamine to external layers.     

Highly Pathogenic Avian Influenza A(H5N8) Virus Spread by Short- and Long-Range Transmission,France, 2016–17

We detected 3 genotypes of highly pathogenic avian influenza A(H5N8) virus in France during winter 2016–17. Genotype A viruses caused dramatic economic losses in the domestic duck farm industry in southwestern France. Our phylogenetic analysis suggests that genotype A viruses formed 5 distinct geographic clusters in southwestern France. In some clusters, local secondary transmission might have been started by a single introduction. The intensity of the viral spread seems to correspond to the density of duck holdings in each production area. To avoid the introduction of disease into an unaffected area, it is crucial that authorities limit the movements of potentially infected birds.     

Management of lung transplantation in the COVID-19 era—An international survey

It is unknown if solid organ transplant recipients are at higher risk for severe COVID-19. The management of a lung transplantation (LTx) program and the therapeutic strategies to adapt the immunosuppressive regimen and antiviral measures is a major issue in the COVID-19 era, but little is known about worldwide practice. We sent out to 180 LTx centers worldwide in June 2020 a survey with 63 questions, both regarding the management of a LTx program in the COVID-19 era and the therapeutic strategies to treat COVID-19 LTx recipients. We received a total of 78 responses from 15 countries. Among participants, 81% declared a reduction of the activity and 47% restricted LTx for urgent cases only. Sixteen centers observed deaths on waiting listed patients and eight centers performed LTx for COVID-19 disease. In 62% of the centers, COVID-19 was diagnosed in LTx recipients, most of them not severe cases. The most common immunosuppressive management included a decreased dose or pausing of the cell cycle inhibitors. Remdesivir, hydroxychloroquine, and azithromycin were the most proposed antiviral strategies. Most of the centers have been affected by the COVID-19 pandemic and proposed an active therapeutic strategy to treat LTx recipients with COVID-19.     

Functional roles of membrane glycoprotein CD36

Cell-cell and cell-extracellular matrix interactions are mediated by a number of membrane glycoproteins. On the basis of structural homologies, several families of cell adhesion molecules (integrins, selectins, immunoglobulins, cadherins, leucine-rich glycoproteins) have been established. Since 1991, a new family of CD36-like proteins has been identified. CD36 is a cell surface glycoprotein that interacts with a large variety of ligands. CD36 has been implicated in thrombosis, vascular biology, lipid metabolism and atherogenesis. In this review, we aim to summarize our present knowledge on this important, multifunctional glycoprotein.     

Increased hospital length of stay attributable to Clostridium difficile infection in patients with four co-morbidities: an analysis of hospital episode statistics in four European countries

Hospital-onset Clostridium difficile infection (CDI) places a significant burden on health care systems throughout Europe, estimated at around €3 billion per annum. This burden is shared between national payers and hospitals that support additional bed days for patients diagnosed with CDI while in hospital or patients re-admitted from a previous hospitalisation. This study was performed to quantify additional hospital stay attributable to CDI in four countries, England, Germany, Spain, and The Netherlands, by analysing nationwide hospital-episode data. We focused upon patients at increased risk of CDI: with chronic obstructive pulmonary disease, heart failure, diabetes, or chronic kidney disease, and aged 50 years or over. Multivariate regression and propensity score matching models were developed to investigate the impact of CDI on additional length of hospital stay, controlling for confounding factors such as underlying disease severity. Patients in England had the longest additional hospital stay attributable to CDI at 16.09 days, followed by Germany at 15.47 days, Spain at 13.56 days, and The Netherlands at 12.58 days, derived using regression analysis. Propensity score matching indicated a higher attributable length of stay of 32.42 days in England, 15.31 days in Spain, and 18.64 days in The Netherlands. Outputs from this study consistently demonstrate that in European countries, for patients whose hospitalisation is complicated by CDI, the infection causes a statistically significant increase in hospital length of stay. This has implications for optimising resource allocation and budget setting at both the national and hospital level to ensure that levels of CDI-complicated hospitalisations are minimised.     

The management of stroke in Phnom Penh, Cambodia

Stroke ranks first among nervous pathologies in Kampuchea. It's a main cause of disability and mortality in our country. We conducted a prospective study including 100 patients hospitalized in the service of general medicine at the Calmette hospital in Phnom Penh. We analyzed the principal risk factors, clinical signs, nature of stroke, complications and markers of the vital and functional prognosis. This work shows the difficulties encountered in the initial care of stroke: delay or absence of hospitalization, cost of complementary examinations to be carried out to determine the nature and the aetiology of stroke and very low level of follow-up to ensure secondary prevention and functional rehabilitation. It can be explained in part by the socioeconomic and cultural level. Research like this one which assesses local needs for stroke prevention, treatment and rehabilitation should be conducted in developing countries to inform the planning and allocation of health care resources in order to reduce the burden of illness associated with stroke. The progressive improvement of the medical structures, and of the socioeconomic and cultural level will facilitate stroke care management.     

Identification and characterization of human Rad51 inhibitors by screening of an existing drug library

Homologous Recombination (HR) plays an essential role in cellular proliferation and in maintaining genomic stability by repairing DNA double-stranded breaks that appear during replication. Rad51, a key protein of HR in eukaryotes, can have an elevated expression level in tumor cells, which correlates with their resistance to anticancer therapies. Therefore, targeted inhibition of Rad51 through inhibitor may improve the tumor response to these therapies. In order to identify small molecules that inhibit Rad51 activity, we screened the Prestwick Library (1120 molecules) for their effect on the strand exchange reaction catalyzed by Rad51. We found that Chicago Sky Blue (CSB) is a potent inhibitor of Rad51, showing IC₅₀ values in the low nanomolar range (400 nM). Biochemical analysis demonstrated that the inhibitory mechanism probably occurs by disrupting the Rad51 association with the single-stranded DNA, which prevents the nucleoprotein filament formation, the first step of the protein activity. Structure Activity Relationship analysis with a number of compounds that shared structure homology with CSB was also performed. The sensitivity of Rad51 inhibition to CSB modifications suggests specific interactions between the molecule and Rad51 nucleofilament. CSB and some of its analogs open up new perspectives in the search for agents capable of potentiating chemo- and radio-therapy treatments for cancer. Moreover, these compounds may be excellent tools to analyze Rad51 cellular functions. Our study also highlights how CSB and its analogs, which are frequently used in colorants, stains and markers, could be responsible of unwanted side effects by perturbing the DNA repair process.