Distinct regulation of tonsillar immune response in virus infection

Cataloged from PDF version of article.Background: The relationships between tonsillar immune responses, and viral infection and allergy are incompletely known. Objective To study intratonsillar/nasopharyngeal virus detections and in vivo expressions of T-cell- and innate immune response-specific cytokines, transcription factors, and type I/II/III interferons in human tonsils. Methods: Palatine tonsil samples were obtained from 143 elective tonsillectomy patients. Adenovirus, bocavirus-1, coronavirus, enteroviruses, influenza virus, metapneumovirus, parainfluenza virus, rhinovirus, and respiratory syncytial virus were detected using PCR. The mRNA expression levels of IFN-α, IFN-β, IFN-γ, IL-10, IL-13, IL-17, IL-28, IL-29, IL-37, TGF-β, FOXP3, GATA3, RORC2, and Tbet were directly analyzed by quantitative RT-PCR. Results Fifty percentage of subjects reported allergy, 59% had ≥1 nasopharyngeal viruses, and 24% had ≥1 intratonsillar viruses. Tonsillar virus detection showed a strong negative association with age; especially rhinovirus or parainfluenza virus detection showed positive association with IFN-γ and Tbet expressions. IL-37 expression was positively associated with atopic dermatitis, whereas IFN-α, IL-13, IL-28, and Tbet expressions were negatively associated with allergic diseases. Network analyses demonstrated strongly polarized clusters of immune regulatory (IL-10, IL-17, TGF-β, FOXP3, GATA3, RORC2, Tbet) and antiviral (IFN-α, IFN-β, IL-28, IL-29) genes. These two clusters became more distinctive in the presence of viral infection or allergy. A negative correlation between antiviral cytokines and IL-10, IL-17, IL-37, FOXP3, and RORC2 was observed only in the presence of viruses, and interestingly, IL-13 strongly correlated with antiviral cytokines. Conclusions: Tonsillar cytokine expression is closely related to existing viral infections, age, and allergic illnesses and shows distinct clusters between antiviral and immune regulatory genes. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Evaluation de l’état trophique des eaux du complexe lagunaire côtier du Sud-Ouest Bénin en période de hautes eaux (de Togbin à l’Embouchure Mono)

Les lagunes servent de tanières pour un grand nombre d’espèces aquatiques et constituent de ce fait des richesses à entretenir. Malheureusement, la lagune côtière du Bénin fait face à un déséquilibre écologique qui se manifeste par une croissance excessive des végétaux aquatiques. En vue de caractériser l’état trophique de la lagune, une campagne d’échantillonnage a été effectuée en période de hautes eaux sur onze points représentatifs. La méthodologie de dosage au spectrophotomètre a été adoptée pour mettre en évidence les paramètres de diagnostic de pollution. Les analyses signalent de fortes concentrations en phosphore (28,75 mg/L) et en nitrites (10 mg/L) dans les eaux de la lagune. La lagune se trouve alors dans un état d’hyper-eutrophisation selon la grille de qualité établie par Ifremer. Le non-respect des mesures de protection des plans d’eau et la mauvaise gestion des déchets ménagers et des eaux usées entraînent la prolifération des nutriments responsables de l’eutrophisation de la lagune côtière. Vu l’ampleur de la pollution mise en relief par cette étude, l’institution d’un programme de surveillance s’avère indispensable afin de veiller au maintien de la qualité écologique des écosystèmes aquatiques en République du Bénin.Mots clés : Lagune côtière, eutrophisation, nutriments, pollution. English Title: Assessment of the trophic state of the waters of the coastal lagoon complex of Southwest Benin during high water periods (from Togbin to Mono Mouth)The lagoons serve as places of residence for several aquatic species and therefore constitute riches to be properly maintained. Unfortunately, the coastal lagoon of Benin faces an ecological imbalance visibly manifested by an excessive growth of aquatic plants. In order to characterize the trophic state of the lagoon, a sampling campaign was carried out during high water periods according to eleven representative points. The spectrophotometer assay methodology was adopted to highlight the pollution diagnostic parameters. Analyzes report high concentrations of phosphorus (28.75 mg/L) and nitrites (10 mg/L) in lagoon waters. The lagoon is then in an enlarged state according to the quality grid established by Ifremer. Failure to comply with measures to protect water bodies and poor management of household waste and wastewater lead to the proliferation of nutrients responsible for eutrophication within the coastal lagoon. Given the magnitude of the pollution highlighted by this study, the implementation of a monitoring program is essential in order to ensure the maintenance of the ecological quality of aquatic ecosystems in the Republic of Benin.Keywords: Coastal lagoon, eutrophication, nutrients, pollution

Detecting Distal Radius Fractures Using a Segmentation-Based Deep Learning Model

Deep learning algorithms can be used to classify medical images. In distal radius fracture treatment, fracture detection and radiographic assessment of fracture displacement are critical steps. The aim of this study was to use pixel-level annotations of fractures to develop a deep learning model for precise distal radius fracture detection. We randomly divided 3785 consecutive emergency wrist radiograph examinations from six hospitals to a training set (3399 examinations) and test set (386 examinations). The training set was used to develop the deep learning model and the test set to assess its validity. The consensus of three hand surgeons was used as the gold standard for the test set. The area under the ROC curve was 0.97 (CI 0.95-0.98) and 0.95 (CI 0.92-0.98) for examinations without a cast. Fractures were identified with higher accuracy in the postero-anterior radiographs than in the lateral radiographs. Our deep learning model performed well in our multi-hospital and multi-radiograph system manufacturer settings. Thus, segmentation-based deep learning models may provide additional benefit. Further research is needed with algorithm comparison and external validation.Peer reviewe

Financing the future of WHO

WHO\u27s resources have consistently lagged behind its constitutional mandate. There is a deep misalignment between what governments and the public expect WHO to do and what the organisation is resourced to do. WHO is challenged by low levels of political will to increase its financing, strained government treasuries, and a battle over control of priorities. WHO\u27s Executive Board has charged the Working Group on Sustainable Financing with identifying a viable plan for sustainable financing before the World Health Assembly in May. There is no time to lose. WHO\u27s resourcing strategy must match its mission with assured financial support from member states buttressed by proven, innovative financing methods. By defining its priorities, delivering on them, and being transparent and accountable, WHO can more boldly pursue its public health mission

Attenuated Semliki Forest virus for cancer treatment in dogs : safety assessment in two laboratory Beagles

Background: Dogs suffer from spontaneous tumors which may be amenable to therapies developed for human cancer patients, and dogs may serve as large-animal cancer models. A non-pathogenic Semliki Forest virus vector VA7-EGFP previously showed promise in targeting human tumor xenografts in mice, but the oncolytic capacity of the virus in canine cancer cells and the safety of the virus in higher mammals such as dogs, are not known. We therefore assessed the oncolytic potency of VA7-EGFP against canine cancer cells by infectivity and viability assays in two dog solid tumor cell lines. Furthermore we performed a 3-week safety study in two adult Beagles which received a single intravenous injection of similar to 2 x 10(5) plaque forming units of parental A7(74) strain. Results: VA7-EGFP was able to replicate in and kill both canine cancer cell lines tested. No adverse events were observed in either of the two virus-injected adult Beagles and no infective virus could be recovered from any of the biological samples collected over the course of the study. Neutralizing antibodies to Semliki Forest virus became detectable in the dogs at 5 days post infection and remained elevated until study termination. Conclusions: Based on these results, testing of the oncolytic potential of attenuated Semliki Forest virus in canine cancer patients appears feasible.Peer reviewe

The WHO’s 75th anniversary: WHO at a pivotal moment in history

The World Health Organisation (WHO) was inaugurated in 1948 to bring the world together to ensure the highest attainable standard of health for all. Establishing health governance under the United Nations (UN), WHO was seen as the preeminent leader in public health, promoting a healthier world following the destruction of World War II and ensuring global solidarity to prevent disease and promote health. Its constitutional function would be ‘to act as the directing and coordinating authority on international health work’. Yet today, as the world commemorates WHO’s 75th anniversary, it faces a historic global health crisis, with governments presenting challenges to its institutional legitimacy and authority amid the ongoing COVID-19 pandemic. WHO governance in the coming years will define the future of the Organisation and, crucially, the health and well-being of billions of people across the globe. At this pivotal moment, WHO must learn critical lessons from its past and make fundamental reforms to become the Organisation it was meant to be. We propose reforms in WHO financing, governance, norms, human rights and equity that will lay a foundation for the next generation of global governance for health

Common cold in Team Finland during 2018 Winter Olympic Games (PyeongChang): Epidemiology, diagnosis including molecular point-of-care testing (POCT) and treatment

Objectives: The common cold is the main cause of medical time loss in elite sport. Rapid diagnosis has been a challenge that may be amenable to molecular point-of-care testing (POCT).Methods: We performed a prospective observational study of the common cold in Team Finland during the 2018 Winter Olympic Games. There were 44 elite athletes and 68 staff members. The chief physician recorded the symptoms of the common cold daily on a standardised form. Two nasal swabs were taken at the onset of symptoms. One swab was analysed within 45 min using a molecular POCT for respiratory syncytial virus and influenza A and B viruses. After the Games, the other swab was tested for 16 possible causative respiratory viruses using PCR in laboratory-based testing.Results: 20 out of 44 (45%) athletes and 22 out of 68 (32%) staff members experienced symptoms of the common cold during a median stay of 21 days. Eleven (26%) samples tested virus-positive using POCT. All subjects with influenza (n=6) and 32 close contacts were treated with oseltamivir. The aetiology of the common cold was finally detected in 75% of the athletes and 68 % of the staff members. Seven virus clusters were identified. They were caused by coronaviruses 229E, NL63 and OC43, influenza B virus, respiratory syncytial virus A, rhinovirus and human metapneumovirus. The virus infections spread readily within the team, most commonly within the same sport discipline.Conclusions: The cold was indeed a common illness in Team Finland during the Winter Olympic Games. POCT proved to be clinically valuable, especially for influenza. The aetiology of the common cold was identified in most cases.</p

Genetic relatedness of infecting and reinfecting respiratory syncytial virus strains identified in a birth cohort from rural Kenya

Background: Respiratory syncytial virus (RSV) reinfects individuals repeatedly. The extent to which this is a consequence of RSV antigenic diversity is unclear. Methods: Six-hundred thirty-five children from rural Kenya were closely monitored for RSV infection from birth through 3 consecutive RSV epidemics. RSV infections were identified by immunofluorescence testing of nasal washing samples collected during acute respiratory illnesses, typed into group A and B, and sequenced in the attachment (G) protein. A positive sample separated from a previous positive by ≥14 days was defined as a reinfection a priori. Results: Phylogenetic analysis was undertaken for 325 (80%) of 409 identified infections, including 53 (64%) of 83 reinfections. Heterologous group reinfections were observed in 28 episodes, and homologous group reinfections were observed in 25 episodes; 10 involved homologous genotypes, 5 showed no amino acid changes, and 3 were separated by 21–24 days and were potentially persistent infections. The temporal distribution of genotypes among reinfections did not differ from that of single infections. Conclusions: The vast majority of infection and reinfection pairs differed by group, genotype, or G amino acid sequence (ie, comprised distinct viruses). The extent to which this is a consequence of immune memory of infection history or prevalent diversity remains unclear

Increased dopamine release after working-memory updating training: Neurochemical correlates of transfer

AbstractPrevious work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the letter-memory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.</div