Parameters Controlling The Initiation Of Replication Of Coronavirus Jhm In Cells Of The Central Nervous System

Parameters controlling the initiation of replication of the neurotropic Coranavirus JHMV were investigated to further elucidate the determinants conferring permissiveness or resistance of cells from the central nervous system. Two fines of enquiry pertaining to the early events of JHMV infection were investigated.;One aspect, the mechanism of JHMV penetration into host cells was examined with the fully permissive L-2 fibroblasts as the host. Several inhibitors including phenylarsine oxide, chlorpromazine, trifluoperazine, hypertonic solution and bafilomycin A1 affecting various stages of the endocytic pathway were used to affect penetration. These experimental approaches revealed that most probably JHMV is internalized through receptor-mediated endocytosis so as to initiate the infectious process within early rather than late acidic endosomes.;The second topic dealt with an early event restricting infection in mature oligodendrocytes. Upregulation in expression of the regulatory R1 subunit of cAMP-dependent protein kinase A; associated with maturation of these host cells, caused inhibition of a phosphoprotein phosphatase (PPPase) associated with endosomes. This activity can dephosphorylate in vitro nucleocapsid (N) protein of JHMV leading to an investigation of a modulation of JHMV replication by R1 and PPPase. Inhibition with calyculin A, revealed that dephosphorylation of N is catalysed by a type 2A PPPaase and occurs during penetration and uncoating of inoculum virions. A correlation between high levels of R1 in L-2 and inhibition of dephosphorylation of N with coincident reduction of JHMV replication, suggests that normally JHMV inoculum is uncoated after entering early endosomes due to dephosphorylation of N. By preventing the uncoating process the R subunit interferes with initiation of replication.;Additional but unrelated studies examined the significance of the amino acid sequence relatedness between N, and microtubule-associated protein (MAP) tau which is axon-specific, and another, MAP4, present in neurites in the trafficking of JHMV within neurons. Using material obtained from the neuronal cell line OBL-21, it was shown that sequence relatedness between N, the MAPs extended to immunological cross-reactivity. By demonstrating that N can interact in vitro with purified tubulin, due to a mimicry there may exist a functional basis for the association between N and microtubules within neurons, as revealed by the electron microscope.;The results of this study imply that, due to their nature as obligatory parasites, viruses have evolved strategies adapted towards utilization of host specific structures and functions necessary for their replication in selected organs such as the CNS

Co-innovation by KIBS in environmental services : a resource-based view

This paper investigates the ability of knowledge intensive business firms (KIBS) to engage in co-innovation with client firms. Co-innovation relates to KIBS competitive advantage as knowledge creators and sources of innovation. We propose a resource-based model where knowledge-related resources and capabilities explain why certain KIBS firms are able to co-innovate. We explore the model on a sample of Dutch environmental investigation firms. Our exploratory results confirm the expected dominant role played by the learning capabilities of KIBS firms in explaining their ability to co-innovate

Comparison of efficacy of injection ferric carboxymaltose and iron sucrose in moderate anaemia in pregnancy

Background: Prevalence of anaemia in pregnant women is 14% in developed and 58-89.6% in pregnant Indian women. Parenteral iron is seems to be an option in the treatment of moderate iron deficiency anaemia which allow high doses of iron to be administered rapidly, in those who are intolerant to oral iron, have  poor compliance to oral iron or gastrointestinal disorder. The objective was to compare the efficacy of newer drug, inravenous ferric carboxymaltose (FCM) with intravenous iron sucrose.Methods: Group A were given injection FCM and group B were given injection iron sucrose. FCM was given in one or two sittings depending on iron requirement and iron sucrose was given in divided doses. Haemogram was done at baseline and on day 3 and 21 and at 12 weeks. All the observations were tabulated and analysed.Results: The mean rise in haemoglobin values from baseline in the FCM group was 0.20±0.06 at 3rd day, 2.03±0.47 at 3 weeks, 3.86±0.53 at 12 weeks compared to iron sucrose group, which was 0.11±0.08 at 3rd day, 1.51±0.39 at 3 weeks, and 3.22±0.54 at 12 weeks, which was statistically significant and showed that the haemoglobin levels were increased more in FCM group. Target haemoglobin was achieved in 92% women in FCM group and 78% women in iron sucrose group.Conclusions: Women in the FCM group achieved significantly higher haemoglobin level than in iron sucrose group. It was given in fewer sittings, hence was more convenient with better efficacy

Wound grading and surgical site infection following caesarean section

Background: Surgical site infection (SSI) following caesarean section can adversely influence the postpartum period for the women. The objective of the study was to study the extent of infection and the microbiological flora in cases of surgical site infection following caesarean section.Methods: Women undergoing caesarean section amongst women admitted in labour ward were followed till discharge for any surgical site infection Detailed assessment of the wound was done. Any discharge if present was taken for culture.Results: 88.88% had normal wound healing, implying no infection. Of those with abnormal wound, 22% had serosanguinous or purulent discharge. Most had superficial incisional SSI. Enterococcus faecalis and Staphylococcus were the commonest organisms grown on culture.Conclusions: All surgical site infections should be looked into as early as possible and managed appropriately

PHARMACOVIGILANCE IN THE ERA OF COVID-19: A CONCISE REVIEW OF THE CURRENT SCENARIO, IMPLICATIONS, AND CHALLENGES

The pandemic of Coronavirus Disease 2019 (COVID-19) has now affected the entire globe which was first surfaced in China in December 2019. In absence of effective therapy to manage COVID-19, repurposed therapies were being used to manage the condition. In view of an urgent need for definitive therapy, multiple repurposed drugs, and investigational drug candidates are being tried in clinical trials which may lead to the emergence of unknown short term and long term adverse drug reactions (ADRs), and hence it is crucial to assess the safety of the tried therapeutic interventions. The lag in the pharmacovigilance activities in the midst of this pandemic fosters under-reporting of ADRs. Difficulty in causality assessment due to factors like wide variations in clinical presentation, concomitant use of multiple drugs, associated comorbidities, drug-drug and drug-disease interaction which forestalls the appropriate causality assessment. Hydroxychloroquine, a repurposed antimalarial drug has been a part of hue and cry at present because of its in-question safety in patients with cardiac disorders. National and International Drug monitoring centers have stressed upon reporting of ADRs and to boost up the process and come up with various recommendations. We can overcome these issues by working cohesively, motivating HCPs and patients to report ADRs electronically, and by setting up dedicated pharmacovigilance rapid response team to tackle the issues at the earliest

An agenda for sustainability transitions research: state of the art and future directions

Research on sustainability transitions has expanded rapidly in the last ten years, diversified in terms of topics and geographical applications, and deepened with respect to theories and methods. This article provides an extensive review and an updated research agenda for the field, classified into nine main themes: understanding transitions; power, agency and politics; governing transitions; civil society, culture and social movements; businesses and industries; transitions in practice and everyday life; geography of transitions; ethical aspects; and methodologies. The review shows that the scope of sustainability transitions research has broadened and connections to established disciplines have grown stronger. At the same time, we see that the grand challenges related to sustainability remain unsolved, calling for continued efforts and an acceleration of ongoing transitions. Transition studies can play a key role in this regard by creating new perspectives, approaches and understanding and helping to move society in the direction of sustainability

Associations Between Childhood Maltreatment and Young Adult Romantic Relationships: A Focus on Gender Differences

Two recent studies investigated the associations between experiencing maltreatment in childhood and dating aggression and interpersonal problems in young adult romantic relationships, with a focus on gender differences

How do sectors change? : The role of incumbents as institutional entrepreneurs

In a societal transition towards sustainability incumbents are often viewed as unwilling or unable to change, or even as actors that intentionally block change processes. This dissertation focuses on the potential role of incumbents in successfully impacting a societal transition towards sustainability by studying the motivations and actions of incumbents acting as institutional entrepreneurs in specific sectors. Which actors take up the role as institutional entrepreneur in the process of sectoral change? Generally the innovation literature points at new innovative firms that try to enter an existing sector with new technologies that radically deviate from the existing knowledge base in the sector: so called discontinuous innovations. It is commonly not expected that insiders or incumbents are a source of discontinuous innovation, as incumbents have strong, vested interests in the existing sectoral innovation system and are therefore not looking for changes that can potentially overthrow this. However, the assumptions regarding the inertia of incumbents might be exaggerated. Several resources related to institutional entrepreneurship are authority, power, legitimacy, and economic capital. Contrary to new innovative firms, incumbents are more likely to possess these resources. Therefore, the focus in this dissertation is on the work incumbents undertake to attempt to enact institutional change. Four case studies have been performed in three different sectors: the greenhouse horticulture sector, the built environment sector (as mature sectors with strongly institutionalized settings) and the bio-plastics sector (as an emerging sector with an emerging institutional setting). Motivations and strategies of incumbents acting as institutional entrepreneurs will likely differ between mature and emerging institutional settings. In mature settings there are clear institutions guiding behavior and limiting change, while emerging settings have more room for actors to create institutions. While there are some methodological differences between the chapters, the overall research design follows a qualitative case study approach. The main finding is that incumbents act as institutional entrepreneurs partly because their view on what constitutes legitimate behavior changes and partly because there are no clear or dominant pressures determining what constitutes legitimate behavior in certain settings. Their view on legitimate behavior can change following their multiple embeddedness in different institutional fields. For instance, several managers placed more importance on sustainability after becoming parents. The lack of clear institutional pressures in emerging fields provides room for institutional entrepreneurs to shape institutions. Incumbents act as institutional entrepreneurs by (un)intentionally pressuring the existing system through collective actions. In projects, collaborations, and strategic alliances the incumbents further develop and diffuse their vision. The success of these collective actions puts pressure on existing sectors. Firms developing discontinuous innovations should be on “making the pie bigger, instead of fighting for the same piece”. As collective actions are important for establishing and diffusing new institutions, there should be legal room for such actions. When deciding to allow or support collective actions, it is crucial to view these actions in light of their contribution to specific sustainability dimensions and to determine whether these actions are discontinuous in nature rather than incremental changes in line with the current system