CMV Infection Epidemiology and Pathogenesis

CMV Infection Epidemiology and Pathogenesis Virus Strain Variation An important variable that may impact the prognosis of infection may be viral strain variation. It has been hypothesized that some clinical strains of CMV are intrinsically more harmful, based on variability in genes implicated in viral pathogenesis. Some subtypes of CMV classified on the basis of their UL144 (TNF receptor homolog) sequence were described as being more likely to be associated with symptomatic disease (Arav-Boger etal., 2006), irrespective of the viral load. On the other hand, other studies were unable to confirm any association with UL144 genotype and the outcome of infection. No differences in clinical outcome could be attributed to variants of the CK homologs, UL146 and UL147 (Heo etal., 2008). When genotypes based on the sequence heterogeneity in the envelope glycoprotein gene, gN (UL73), were compared, congenital infection with one genotype, gN-1, was associated with an improved prognosis with respect to long-term neurodevelopmental sequelae (Pignatelli etal., 2003). In another study of infants with congenital infection, the distribution of genotypes for the gB glycoprotein gene (UL55) showed significant differences, depending upon the disease classification observed, but no information was reported on long-term neurodevelopmental sequelae (Jin etal., 2007). Differences in virulence between strains of HCMV may reflect their abilities to attach to cells. HCMV strains Toledo (low passage in cell culture), Towne and AD169 (cell culture-adapted) exhibited differences in virulence in vaccinated volunteers. Growth differences relative to virulence of the various HCMV isolates have also been observed in endothelial cells. Differences in glycoproteins may be the reason for the differences in abilities to attach and replicate in cells. HCMV was originally classified into four genotypes of gB, each with a characteristic nucleotide and peptide sequence, but later, a fifth glycoprotein genotype has been identified (Sweet, 1999). Clinical HCMV isolates are slower growing on human fibroblast cells and differ from laboratory adapted strains of HCMV in that they encode additional sequences in the ULb locus (about 19kb), which is believed to be associated with viral pathogenicity and/or the ability of the virus to grow on epithelial/endothelial cells (Hahn et al., 2004). This locus is rapidly mutated and deleted in the process of adaptation of the virus to tissue culture fibroblast cells (Dargan et al., 2010). The UL128-131 genes in the ULb locus have been demonstrated to be necessary for virus entry into epithelial and endothelial cells by a newly identified endocytic method of cell entry that is different from the pathway of infection in fibroblast cells (Ryckman et al., 2006). Epidemiology Human CMV is an ancient virus that is ubiquitous in human populations, reaching a prevalence of 100% in Africa and Asia, and approximately 80% in Europe and the USA, depending on socioeconomic status (Cannon et al., 2010). CMV infection is widespread and occurs worldwide. (Bate et al., 2010). Seroprevalence rates vary depending on age (higher rates are observed among older persons), geography (higher rates in developing countries), and socioeconomic status (higher rates in economically depressed regions) (Bate et al., 2010, and Cannon etal., 2010). Primary CMV infection occurs most commonly during the first 2 decades of life (Joseph et al., 2006). Non-white race, low socio-economic status, premature birth, and neonatal intensive care unit admittance are among the important risk factors for congenital CMV infection (Kenneson and Cannon, 2007).Congenital CMV infection can occur in 0.5-2% of all pregnancies, often with devastating consequences for the developing fetus (Sung and Schleiss, 2010). Among congenitally infected infants, approximately 10% have signs and symptoms of disease at birth. Although the remaining 90% of infants are asymptomatic at birth, 10-15% will subsequently develop permanent sequelae, including sensorineural hearing loss and mental retardation (Cheeran et al., 2009). It has been reported that 25% of congenitally infected infants whose mother had a primary HCMV infection during pregnancy had at least one sequela, compared with 8% in infants born to women with recurrent infection (Sung and Schleiss, 2010). The impact of congenital CMV is greater in the developed world because of the number of CMV negative wo men of child bearing age and the risk of primary infection during pregnancy which substantially increases the likelihood of congenital infection (Colugnati et al., 2007). In the developed world, congenital HCMV is the second most common cause of mental retardation next to Downs syndrome (Dollard et al., 2007). Additionally, HCMV related deafness occurs at a greater frequency than that related to Hemophilus influenza infection in the preHIB vaccine era (McGregor and Choi, 2015). Transplacental transmission of virus occurs in about one-third of mothers with primary CMV infection (Kenneson and Cannon, 2007), and approximately one-half of these infections in utero result in a symptomatic clinical syndrome (Adler et al., 2007). Epidemiological data suggest that the timing of acquisition of primary infection relative to the establishment of pregnancy is an important factor in establishing the risk to the fetus for in utero transmission (Revello et al., 2006). The infection is acquired by 40% of children within the first decade of life. Seroprevalence increases to 80% by the age of 60 (Kenneson and Cannon, 2007). Most HIV-infected individuals are seropositive for CMV. HIV infection accelerates the development of CMV-dependant immunological abnormalities (Barrett et al., 2012). In Africa, the prevalence of CMV IgG among HIV-negative adults was 81.8% (range 55-97%). For HIV-infected adults the pooled CMV IgG seroprevalence was lower among those with clinically defined AIDS (81.9%, range 59-100%) than among asymptomatic HIV-infected adults (94.8%, range 71-100%), consistent with the notion of weaker humoral responses associated with AIDS progression. It is also possible that some non-HIV infected adults are infected but do not mount a measurable IgG response. Among pregnant women seroprevalence mirrored that among healthy blood donors, although the HIV status of participants was not always stated. In children, pooled seroprevalence was 88.1% (range 80-100%). With this very high seroprevalence in children, even in very young infants, one would expect seroprevalence among adults to be consistently close to 100% (Bates and Brantsaeter, 2016). In Egypt, the seroprevalence of CMV infection among pregnant women and acute lymphoblastic leukaemic patients was 100%(Bates and Brantsaeter, 2016). Pathogenesis CMV employs at least two distinct, cell-type specific mechanisms of cell entry. Entry of CMV into endothelial and epithelial cells is mediated by endocytosis in a pH-dependent fashion; in contrast, entry into fibroblasts is non-endocytic, and pH-independent. CMV fibroblast entry is believed to be initiated by binding of virion-associated gB to a cell surface receptor, followed by fusion with the cell membrane in a process that requires a complex of three other glycoproteins: gH, gL, and gO (Ryckman etal., 2006). In contrast to the model of CMV entry for fibroblasts, endocytic entry of CMV into endothelial and epithelial cells requires a complex of gH, gL, and three other proteins encoded by a region of the CMV genome referred to as the UL128-131 gene locus (Wang and Shenk, 2005). The pathologic effect of a CMV-encoded gene is believed to be mediated directly by that gene product; in other situations, CMV infection leads to downstream effects on cellular gene expression that then may potentially lead to pathologic outcomes. In many circumstances, CMV gene products mediate more than one pathogenic effect and there is considerable overlap across these categories (Schleiss, 2011). Following infection, the messenger ribonucleic acid (mRNA) for the major 72-kilodalton IE protein is transcribed more abundantly than any other mRNA as a result of an upstream regulatory sequence of DNA that competes more efficiently for ribonucleic acid polymerase 11 (Stinski, 1984). These upstream enhancer sequences constitute the first step in the regulation of CMV gene expression. The 72-kilodalton protein is then transported back to the nucleus, presumably to influence the switch from restricted transcription of the long unique sequence to more extensive transcription. A block in the synthesis of IE proteins disrupts any further transcription of the viral genome, suggesting that these proteins may play a major role in determining whether a CMV infection is latent, persistent, or productive (Spector and Spector, 1984). The pathogenesis of disease associated with acute CMV infection has been attributed to lytic virus replication, with end-organ damage occurring either secondary to virus-mediated cell death or from pathologic host immune responses targeting virus-infected cells (Britt et al., 2008).

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Human dealing with different mission, depending on the job environment and the problem space is called as the processor of information. This concept describes how does the man processes job oriented representational information. Information processing concept mainly describes the processes of human problem solving, features of information system that carries out the processes and the nature of job environment in which the processes function. Definite differences in the behavior by individuals and by responsibilities, and also the general expectedness of intelligent behavior from the requirements of the job are the general features of human behavior. This challenges all attempts to develop human thinking. In human problem solving memory, handling, programs, retrieval time, etc are the main constitutes of information processing system. Each person is a member of inhabitants. Every person differs methodically, unique inherent grant and historical treasure. This study has been studied in detail in this book by developing a discussion on Chess, symbolic logic and algebra like puzzles. Th...

 Benefits of encouraging and rewarding positive behaviour Essay

When it comes to behaviour it can be easy to focus on what we need to stop children from doing. The problem with this approach is that it does not help children know what they should be doing. This means that nowadays there is much more emphasis on encouraging positive behaviour . A good starting point is to think about the positive behaviour or goals that you should be encouraging in children. This may be outlined in your settings policy or you may need to observe what other staff seem to encourage. If you are working in a setting that several ages of children notice the way in which there are different expectations according to the age of the children Why encouraging and rewarding positive behaviour works 1. It helps children to learn what they need to do 2. It creates calmer environment and stronger relationships 3. Children respond well 4. Children learn from adults Skills and techniques for positive behaviour 1. Rewards 2. Attention 3. Praise 4. Star charts 5. Being given responsibility 6. Treats 7. Stickers 8. Timing 9. Explanation 10. Public acknowledged Settings for children and young people Children centres children aged 0-5yrs Day care facilcity children ages 0-5yrs A home setting children aged 0-8yrs Extended care children and young people 4-16yrs Youth activity club young 11-16yrs A reception class ks1 in a primary school A crà ¨che for children up to the age up to 5yrs Attention seeking What a child does Many children show attention seeking behaviour at times . it can be a sign of insecurity or in some cases mean that children have become used to having a lot of adult attention How to deal with it It is often best to ignore attention seeking behaviour unless it is dangerous as by challenging it you may be teaching children that they can get attention this way Biting What a child does Many toddlers bite especially if they are in group care. Biting is often linked to frustration and can become a habit How to deal with it Act immediately Give the victim attention first Once a child has bitten, it is likely that another bite will follow Behaviour problems that should be referred Biting, aggression, change of behaviour ,self-harming, bullying It is unusual for most settings to try a few strategies’ first before referring to other professionals sometimes unwanted behaviour is a result of a medical condition or learning difficulty while others might be linked to emotional difficulty that the child has table 2 shows some of the pros who may support the child and their family. GP family doctor This is often the first part of call as the family doctor will able to refer to others. Health visitor A health visitor may visit the family at home and give some advice. Educational physcologist The educational physcologist will look at the children’s learning and behaviour. Child psychiatrist A child psychiatrist will help children who may have metal health issues. Family counsellor A family counsellor may help work with whole family and child. Play therapist Children who have had some trauma may see a play therapist so that they can work on what has happened.

Comparing the Characters of Faustus and Hamlet - 1767 Words

Both Hamlet and Faustus contain a clash of themes and traditions, all catalysed by Religion. This is used to establish a theme of deception, which greatly impacts the protagonist’s procrastination. Procrastination is considered to be Hamlet’s tragic flaw, however Faustus’s flaw is considered to be his hubris. Hamlet is in fact a play adapted by Shakespeare, not by name. But there are several scriptures that can be identified to being similar to the plot. One is called Saga of Hrolf Kraki. Believed to be Scandinavian. The second is the Roman legend of Brutus. In Shakespeare’s version Hamlet is the prince of Denmark heir to the throne, whose life takes a turn for the worst after his father’s death. This version of Hamlet is the most†¦show more content†¦Therefore we can assume that Faustus is a protestant, but it can be argued that Marlowe could have possibly made this protestant connection in his defence to cease all accusations about him being a practicing catholic. Hence, the scene where Faustus appears to be mocking the pope. â€Å"The pay is built upon Hamlet’s hesitation over fulfilling the task of revenge that is assigned to him: but its text offers no reason or motives for these hesitations† (Sigmund Freud) This comment gives us an insight that Hamlet’s tragic flaw is in fact his procrastination to killing Claudius. Although the literal text does not offer a valid reason for his procrastination, the sub-text imposes a compelling argument. â€Å"I am thy father’s spirit, Doom’d for a certain term to walk the night, and for the day confined to fast in fires, till the foul crimes done in my days of nature are burnt and purged away† (1.5.9) The ghost appears before Hamlet and claims to be the spirit of his father; he also mentions that he is in purgatory. While belief in Purgatory remains part of Roman Catholic teaching today, the Protestant Reformers explicitly rejected it in the sixteenth century1. This suggests that the ghost is a catholic, which may not have made a difference to Hamlet’s character, however although the plays story is set in the late middle ages (before the Protestant Reformation),Show MoreRelatedShift from Medieval Scholasticism to Humanism800 Words   |  3 Pagesthe origins of what would later come to be known as the humanities (Kristeller, 1965). It can be viewed as the fulfilment of life through reason and science, as opposed to religion and faith. The protagonists found in Shakespeares Hamlet and Marlowes Dr. Faustus can be seen as literary explorers in the shift from medieval schloasticism to humanism - each embodying the ideals of humanist thought. Prior to the societal shift away from the scholasticism which had become so evident, most productionsRead MoreThe Function Of The Tragic Greek Chorus1295 Words   |  6 PagesIn â€Å"The Function of the Tragic Greek Chorus Theatre,† Albert Weiner, who is known for editing Hamlet: The First Quarto, 1603, explains that the Chorus in Greek drama was a troupe of actors who described and commented on the main action of the play through song, dance and recitation (205). Weiner goes on to explain that Greek tragedy began with choral performances dating back to the 5th century B.C. (205). In Weiner’s article, he pulls a quote from Chapter 18 of Aristotle’s Poetics, where Aristotle