The Use of Aerosolized Ribavirin in Respiratory Syncytial Virus Lower Respiratory Tract Infections in Adult Immunocompromised Patients: A Systematic Review

Introduction: Respiratory syncytial virus (RSV)–associated lower respiratory tract infection (LRTI) is a concern in immunocompromised patients. Aerosolized ribavirin (RBV AER) is used for treatment of RSV LRTI; however, adverse events and rising drug costs remain a challenge for patient management. The purpose of this systematic review is to summarize the efficacy and adverse event profile of RBV AER for the treatment of hospitalized RSV LRTI in immunocompromised adult patients. Methods: A Medline/PubMed, Embase, Google Scholar, Clinicaltrials.gov, and Cochrane Library database search was conducted from 1966 to January 2019 for the use of RBV AER. Search strategy: [(ribavirin OR ICN1229) AND (“administration, oral” OR “oral” OR “administration, inhalation” OR “inhalation)] AND (“respiratory tract infection” OR “pneumonia”). Studies were reviewed if adult patients were hospitalized, immunocompromised, had RSV LRTI, received RBV AER, and included the outcome of mortality and/or adverse reactions. Methodological quality was assessed using the Cochrane Collaboration GRADE approach. Results: A total of 1787 records were identified and 15 articles met inclusion criteria: hematopoietic stem cell transplant (HSCT)/bone marrow transplant (n = 8), other malignancy/neutropenic (n = 2), solid organ transplant (n = 5). All of the trials are observational with a low quality rating; therefore, a meta-analysis was not performed. The 30-day mortality in studies that contain \u3e10 patients with HSCT, malignancy, and transplant range from 0 to 15.4%, 6.3%, and 0 to 27%, respectively. Improved mortality was cited in 4 studies when RBV AER started before mechanical ventilation or within 2 weeks of symptom onset. Only 3 studies had comparative mortality data with RBV AER and RBV PO. Adverse reactions were reported in 5 studies and included psychiatric manifestations (anxiety, depression, feeling of isolation; n = 14), wheezing/bronchospasm (n = 6), snowflakes/hail blowing in face (n = 6), and precipitation in ventilator tubing (n = 5). Conclusion: There is a lack of high quality, comparative trials on the use of RBV AER for the treatment of RSV LRTI in adult hospitalized immunocompromised patients. There may be a mortality benefit when RBV AER is initiated early after diagnosis or prior to mechanical ventilation, but requires further study. Patient isolation and psychological effects must be weighed against the benefit of therapy

Intramolecular integration within Moloney murine leukemia virus DNA

By screening a library of unintegrated, circular Moloney murine leukemia virus (M-MuLV) DNA cloned in lambda phage, we found that approximately 20% of the M-MuLV DNA inserts contained internal sequence deletions or inversions. Restriction enzyme mapping demonstrated tht the deleted segments frequently abutted a long terminal repeat (LTR) sequence, whereas the inverted segments were usually flanked by LTR sequences, suggesting that many of the variants arose as a consequence of M-MuLV DNA molecules integrating within their own DNA. Nucleotide sequencing also suggested that most of the variant inserts were generated by autointegration. One of the recombinant M-MuLV DNA inserts contained a large inverted repeat of a unique M-MuLV sequence abutting an LTR. This molecule was shown by nucleotide sequencing to have arisen by an M-MuLV DNA Molecule integrating within a second M-MuLV DNA molecule before cloning. The autointegrated M-MuLV DNA had generally lost two base pairs from the LTR sequence at each junction with target site DNA, whereas a four-base-pair direct repeat of target site DNA flanked the integrated viral DNA. Nucleotide sequencing of preintegration target site DNA showed that this four-base-pair direct repeat was present only once before integration and was thus reiterated by the integration event. The results obtained from the autointegrated clones were supported by nucleotide sequencing of the host-virus junction of two cloned M-MuLV integrated proviruses obtained from infected rat cells. Detailed analysis of the different unique target site sequences revealed no obvious common features

An Exploratory Study of a User\u27s Facebook Security and Privacy Settings

There are many potential security risks with social networking sites and the individuals who use them. These sites have been adopted by people of all ages worldwide, empowering new opportunities for the presentation of the self-learning, construction of a wide circle of relationships, and the management of privacy and intimacy. This study analyses the effect of social networking security practices, more specifically Facebook and its security and privacy settings. We identify four hypotheses: The more important Facebook users believe security is an important factor in choosing a social network, the more often they will change their security settings, the more important protection against ID theft is for Facebook users, the more frequently they will change their privacy settings, Facebook users who have left their security on a default setting have more frequently fallen victim to a virus or malware attack, and users of Facebook who have their privacy set to a custom setting are less likely to receive an attack on their profile

Feasibility Test of the MedaCube

Poor adherence is a significant barrier to achieve better patient outcomes. Rates of non-adherence approach 40% resulting in 10% of all emergency department visits and 23% of admissions into skilled nursing facilities. Many factors contribute to medication non-adherence including psychological and memory disorders, aging and pill burden. The MedaCube is a medication management system intended to help solve unintentional medication non-adherence. The device is designed to dispense scheduled and as-needed oral medications. The MedaCube provides audio and visual prompts alerting subjects to administer their medications. Caregivers receive notification of missed doses, late doses and refill requests. The null hypothesis is that use of the MedaCube results in no difference in medication adherence when compared with six month prior adherence in individual subjects

Advances in functional neuroimaging in dementias and potential pitfalls

Neuroimaging is continuously advancing at a rapid rate and has progressed from excluding relatively uncommon secondary causes (stroke, tumor) to assisting with early diagnosis and subtype of dementia. Structural imaging has given way to functional, metabolic and receptor imaging

Interferon regulatory factor 2 protects mice from lethal viral neuroinvasion.

The host responds to virus infection by activating type I interferon (IFN) signaling leading to expression of IFN-stimulated genes (ISGs). Dysregulation of the IFN response results in inflammatory diseases and chronic infections. In this study, we demonstrate that IFN regulatory factor 2 (IRF2), an ISG and a negative regulator of IFN signaling, influences alphavirus neuroinvasion and pathogenesis. A Sindbis virus strain that in wild-type (WT) mice only causes disease when injected into the brain leads to lethal encephalitis in Irf2-/- mice after peripheral inoculation. Irf2-/- mice fail to control virus replication and recruit immune infiltrates into the brain. Reduced B cells and virus-specific IgG are observed in the Irf2-/- mouse brains despite the presence of peripheral neutralizing antibodies, suggesting a defect in B cell trafficking to the central nervous system (CNS). B cell-deficient μMT mice are significantly more susceptible to viral infection, yet WT B cells and serum are unable to rescue the Irf2-/- mice. Collectively, our data demonstrate that proper localization of B cells and local production of antibodies in the CNS are required for protection. The work advances our understanding of host mechanisms that affect viral neuroinvasion and their contribution to immunity against CNS infections

The herpetofauna of the Owen Sitole College of Agriculture, Zululand.

Thesis (M.Sc.)-University of Natal, 1990.A herpetofaunal study was undertaken at the 670 ha Owen Sitole College of Agriculture (OSCA) near Empangeni, Zululand, from 1986 to 1988. Collecting was carried out primarily opportunistically, throughout all seasons. A total of 28 amphibian taxa and 44 reptile taxa, comprising two chelonians, one crocodylid, 13 lizards and 28 snakes, were recorded. A further 11 amphibian and 42 reptile taxa may possibly occur. The majority of amphibians and reptiles display a tropical distribution, often with enormous ranges. Nineteen (68%) amphibian taxa have tropical or quasi-tropical (Poynton 1964) zoogeographical affinities and 33 (75%) reptile taxa have tropical wide ranging or tropical east coast littoral (Bruton and Haacke 1980) zoogeographical affinities. Only one amphibian taxon and four reptile taxa, all snakes, have Cape or temperate affinities. These taxa are marginal in the region, reaching their distributional limits in Maputaland. Niche segregation of amphibians occurs primarily according to water bodies. Vegetation per se does not appear to be important, with the majority of species occurring in a savanna environment; however, three species, Leptopelis natalensis, h. mossambicus and Arthroleptis wahlbergii, appear to be sylvicolous in habits and are restricted to riverine vegetation. The vast majority of taxa are summer breeders, whereas only one, Cacosternum nanum nanum, was recorded breeding in winter too. The syrnpatry of h. natalensis and Hyperolius semidiscus was confirmed in this study, and H. semidiscus and H. argus were shown to behave as good species with specifically distinct calls. Snakes are segregated according to size, mode of life, activity patterns and food. Certain species, such as Naja mossambica, have catholic diets whereas others, such as Duberria lutrix lutrix, Aparallactus capensis and Dasypeltis scabra, are specialists. The lizard fauna is differentiated according to diet, foraging strategies and habitat preferences, including substrate and vegetation. Amphibians are unselective feeders, consuming a variety of insects. Some, namely Xenopus laevis laevis and Pyxicephalus adspersus edulis, have catholic tastes and are even cannibalistic. Snakes and amphibians constitute the main prey items of snakes, whereas most lizards, with the exception of Varanus niloticus niloticus which is a generalist, feed exclusively on arthropods, especially insects. Schismaderma carens, Bufo gutturalis, Hemidactylus mabouia mabouia, Lygodactylus caoensis capensis, Mabuya striata striata, Lamprophis fuliginosus, Causus rhombeatus, Duberria lutrix lutrix and Naja mossambica are attracted to places of human habitation either for feeding or for shelter. Many amphibians benefit from artificial water bodies. No less than 19 taxa were recorded from the fish ponds, the majority of which bred there, possibly because the waters are more stable, permanent and relatively free of predators than natural water bodies. The Leguaan Tick Aponomma exornatum was recorded parasitizing adult Varanus niloticus niloticus, and the Snake Tick A. latum was found on N. mossambica and h. rhombeatus; A. latum, with an extensive subSaharan distribution, shows no predilection for any species of snake. Pentastomids and nematodes were found in a number of snakes (Atractaspis, Telescopus, Psammophis and Causus); the life cycle implications of these organisms are that mammals and snakes are intermediate hosts, though more ecological and experimental evidence is necessary. Python sebae natalens is and Kinixys natalensis, both Red Data Book - Reptile and Amphibian species, are particularly threatened, the first due to slaughter for traditional uses, the second due to agricultural activities and frequent fires. It is recommended that both these reptiles be afforded maximum protection in the 110 ha game park, which is regularly patrolled and which is subjected to infrequent fires. Generally, however, the herpetofauna has fared well at the hands of the local people, testimony to which is the high species diversity

Role of correlated two-pion exchange in K+NK^+ N scattering

A dynamical model for S-- and P--wave correlated $2 \pi$ (and $K \bar K$) exchange between a kaon and a nucleon is presented, starting from corresponding $N \bar N \rightarrow K \bar K$ amplitudes in the pseudophysical region, which have been constructed from nucleon, $\Delta$--isobar and hyperon ($\Lambda$, $\Sigma$) exchange Born terms and a realistic meson exchange model of the $\pi \pi \rightarrow K \bar K$ and $K \bar K \rightarrow K \bar K$ amplitude. The contribution in the s--channel is then obtained by performing a dispersion relation over the unitarity cut. In the $\rho$--channel, considerable ambiguities exist, depending on how the dispersion integral is performed. Our model, supplemented by short range interaction terms, is able to describe empirical $K^+ N$ data below pion production threshold in a satisfactory way.Comment: 24 pages, REVTEX, figures available from the author

Genetic Variation in Mother-Child Acute Seroconverter Pairs from Zambia

Objective: To characterize the envelope (env) glycoprotein of HIV-1 in mother-infant pairs (MIP) that underwent near simultaneous or acute-phase seroconversion, we examined the env sequence of the transmitted viruses and compare viral evolution within the pair. Design: Three MIP from a Zambian cohort that seroconverted at the same sampling time were identified and followed longitudinally. Methods: The V1-V5 region of the HIV-1 env gene was sequenced for each sample collected. Phylogenetic and population genetics analyses were carried out to subtype the viruses, estimate relationships among viral genotypes, and compare molecular evolution between the viral populations. Results: Genetic analyses demonstrated a close intrapair relationship between viral sequences from each MIP. Transmission involved several closely related viral genotypes and did not result in a reduction in viral diversity. Amino acid changes were not evenly distributed along env V1-V5 but concentrated in concordant areas within each MIP. Several positions under positive selection were shared between the MIP viruses. Interestingly, selective pressure on the virus was higher in the infants than in the mothers. Conclusions: In contrast to most cases of perinatal transmission of HIV-1 from chronically infected mothers, there is no evidence of a genetic bottleneck in the transmitted viruses in these three instances of acute seroconversion. The longitudinal changes in the amino acids are in similar positions in env for the MIP, suggesting shared evolutionary constrains among the closely related viruses infecting the MIP; such constrains may lead to similar genetic changes in the virus in two different hosts

Predicting Wolbachia invasion dynamics in Aedes aegypti populations using models of density-dependent demographic traits

Background Arbovirus transmission by the mosquito Aedes aegypti can be reduced by the introduction and establishment of the endosymbiotic bacteria Wolbachia in wild populations of the vector. Wolbachia spreads by increasing the fitness of its hosts relative to uninfected mosquitoes. However, mosquito fitness is also strongly affected by population size through density-dependent competition for limited food resources. We do not understand how this natural variation in fitness affects symbiont spread, which limits our ability to design successful control strategies. Results We develop a mathematical model to predict A. aegypti–Wolbachia dynamics that incorporates larval density-dependent variation in important fitness components of infected and uninfected mosquitoes. Our model explains detailed features of the mosquito–Wolbachia dynamics observed in two independent experimental A. aegypti populations, allowing the combined effects on dynamics of multiple density-dependent fitness components to be characterized. We apply our model to investigate Wolbachia field release dynamics, and show how invasion outcomes can depend strongly on the severity of density-dependent competition at the release site. Specifically, the ratio of released relative to wild mosquitoes required to attain a target infection frequency (at the end of a release program) can vary by nearly an order of magnitude. The time taken for Wolbachia to become established following releases can differ by over 2 years. These effects depend on the relative fitness of field and insectary-reared mosquitoes. Conclusions Models of Wolbachia invasion incorporating density-dependent demographic variation in the host population explain observed dynamics in experimental A. aegypti populations. These models predict strong effects of density-dependence on Wolbachia dynamics in field populations, and can assist in the effective use of Wolbachia to control the transmission of arboviruses such as dengue, chikungunya and zika.</p