Analysis of Risk Factors for Fatal Rocky Mountain Spotted Fever: Evidence for Superiority of Tetracyclines for Therapy

Epidemiologic and clinical characteristics of fatal and nonfatal cases of Rocky Mountain spotted fever (RMSF) were compared to identify risk factors for death caused by this disease. Confirmed and probable RMSF cases reported through US national surveillance for 1981- 1998 were analyzed. Among 6388 RMSF patients, 213 died (annual case-fatality rate, 3M; range, 4.9 % in 1982 to 1.1 % in 1996). Use of tetracycline-class antibiotics for treatment of RMSF increased significantly in the 1990s, compared with use in the 1980s. Older patients, patients treated with chloramphenicol only, patients for whom tetracycline antibiotics were not the primary therapy, and patients for whom treatment was delayed ≥5 days after the onset of symptoms were at higher risk for death. Although the case-fatality rate was lower in the 1990s than in the 1980s, risk factors for fatal RMSF were similar. Despite the availability of effective antibiotics, RMSF-related deaths continue to occur because of delayed diagnosis and failure to use appropriate therapy

Wind-driven ventilation improvement with plan typology alteration: a CFD case study of traditional Turkish architecture

Aligned with achieving the goal of net-zero buildings, the implementation of energy-saving techniques in minimizing energy demands is proving more vital than at any time. As practical and economic options, passive strategies in ventilation developed over thousands of years have shown great potential for the reduction of residential energy demands, which are often underestimated in modern building’s construction. In particular, as a cost-effective passive strategy, wind-driven ventilation via windows has huge potential in the enhancement of the indoor air quality (IAQ) of buildings while simultaneously reducing their cooling load. This study aims to investigate the functionality and applicability of a common historical Turkish architectural element called “Cumba” to improve the wind-driven ventilation in modern buildings. A case study building with an archetypal plan and parameters was defined as a result of a survey over 111 existing traditional samples across Turkey. Buildings with and without Cumba were compared in different scenarios by the development of a validated CFD microclimate model. The results of simulations clearly demonstrate that Cumba can enhance the room’s ventilation rate by more than two times while harvesting wind from different directions. It was also found that a flexible window opening strategy can help to increase the mean ventilation rate by 276%. Moreover, the room’s mean air velocity and ventilation rate could be adjusted to a broad range of values with the existence of Cumba. Thus, this study presents important findings about the importance of plan typology in the effectiveness of wind-driven ventilation strategies in modern dwellings

Analysis of Risk Factors for Fatal Rocky Mountain Spotted Fever: Evidence for Superiority of Tetracyclines for Therapy

Epidemiologic and clinical characteristics of fatal and nonfatal cases of Rocky Mountain spotted fever (RMSF) were compared to identify risk factors for death caused by this disease. Confirmed and probable RMSF cases reported through US national surveillance for 1981- 1998 were analyzed. Among 6388 RMSF patients, 213 died (annual case-fatality rate, 3M; range, 4.9 % in 1982 to 1.1 % in 1996). Use of tetracycline-class antibiotics for treatment of RMSF increased significantly in the 1990s, compared with use in the 1980s. Older patients, patients treated with chloramphenicol only, patients for whom tetracycline antibiotics were not the primary therapy, and patients for whom treatment was delayed ≥5 days after the onset of symptoms were at higher risk for death. Although the case-fatality rate was lower in the 1990s than in the 1980s, risk factors for fatal RMSF were similar. Despite the availability of effective antibiotics, RMSF-related deaths continue to occur because of delayed diagnosis and failure to use appropriate therapy

Formation of a morphine-conditioned place preference does not change the size of evoked potentials in the ventral hippocampus–nucleus accumbens projection

Abstract In opioid addiction, cues and contexts associated with drug reward can be powerful triggers for drug craving and relapse. The synapses linking ventral hippocampal outputs to medium spiny neurons of the accumbens may be key sites for the formation and storage of associations between place or context and reward, both drug-related and natural. To assess this, we implanted rats with electrodes in the accumbens shell to record synaptic potentials evoked by electrical stimulation of the ventral hippocampus, as well as continuous local-field-potential activity. Rats then underwent morphine-induced (10 mg/kg) conditioned-place-preference training, followed by extinction. Morphine caused an acute increase in the slope and amplitude of accumbens evoked responses, but no long-term changes were evident after conditioning or extinction of the place preference, suggesting that the formation of this type of memory does not lead to a net change in synaptic strength in the ventral hippocampal output to the accumbens. However, analysis of the local field potential revealed a marked sensitization of theta- and high-gamma-frequency activity with repeated morphine administration. This phenomenon may be linked to the behavioral changes—such as psychomotor sensitization and the development of drug craving—that are associated with chronic use of addictive drugs

Limiting worker exposure to highly pathogenic avian influenza a (H5N1): a repeat survey at a rendering plant processing infected poultry carcasses in the UK

<p>Abstract</p> <p>Background</p> <p>Current occupational and public health guidance does not distinguish between rendering plant workers and cullers/poultry workers in terms of infection risk in their respective roles during highly pathogenic avian influenza poultry outbreaks. We describe an operational approach to human health risk assessment decision making at a large rendering plant processing poultry carcasses stemming from two separate highly pathogenic avian influenza A (H5N1) outbreaks in England during 2007.</p> <p>Methods</p> <p>During the first incident a uniform approach assigned equal exposure risk to all rendering workers in or near the production line. A task based exposure assessment approach was adopted during the second incident based on a hierarchy of occupational activities and potential for infection exposure. Workers assessed as being at risk of infection were offered personal protective equipment; pre-exposure antiviral prophylaxis; seasonal influenza immunisation; hygiene advice; and health monitoring. A repeat survey design was employed to compare the two risk assessment approaches, with allocation of antiviral prophylaxis as the main outcome variable.</p> <p>Results</p> <p>Task based exposure assessment during the second incident reduced the number of workers assessed at risk of infection from 72 to 55 (24% reduction) when compared to the first incident. No cases of influenza like illness were reported in workers during both incidents.</p> <p>Conclusions</p> <p>Task based exposure assessment informs a proportionate public health response in rendering plant workers during highly pathogenic avian influenza H5N1 outbreaks, and reduces reliance on extensive antiviral prophylaxis.</p

Contributions of the MyD88-Dependent Receptors IL-18R, IL-1R, and TLR9 to Host Defenses following Pulmonary Challenge with Cryptococcus neoformans

Signaling via the adapter protein, MyD88, is important in the host defense against Cryptococcus neoformans infection. While certain Toll-like receptors (TLRs) can enhance the clearance of Cryptococcus, the contributions of MyD88-dependent, TLR-independent pathways have not been fully investigated. We examined the roles of IL-1R and IL-18R in vivo by challenging C57BL/6 mice with a lethal strain of Cryptococcus. We found that the absence of IL-18R, but not IL-1R, causes a shift in the survival curve following pulmonary delivery of a virulent strain of C. neoformans (H99). Specifically, IL-18R-deficient mice have significantly shorter median survival times compared to wild-type mice following infection. Cytokine analysis of lung homogenates revealed that deficiency of IL-IR, IL-18R, or MyD88 is associated with diminished lung levels of IL-1β. In order to compare these findings with those related to TLR-deficiency, we studied the effects of TLR9-deficiency and found that deficiency of TLR9 also affects the survival curve of mice following challenge with C. neoformans. Yet the lungs from infected TLR9-deficient mice have robust levels of IL-1β. In summary, we found that multiple signaling components can contribute the MyD88-dependent host responses to cryptococcal infection in vivo and each drives distinct pulmonary responses

Surface Localization of Glucosylceramide during Cryptococcus neoformans Infection Allows Targeting as a Potential Antifungal

Cryptococcus neoformans (Cn) is a significant human pathogen that, despite current treatments, continues to have a high morbidity rate especially in sub-Saharan Africa. The need for more tolerable and specific therapies has been clearly shown. In the search for novel drug targets, the gene for glucosylceramide synthase (GCS1) was deleted in Cn, resulting in a strain (Δgcs1) that does not produce glucosylceramide (GlcCer) and is avirulent in mouse models of infection. To understand the biology behind the connection between virulence and GlcCer, the production and localization of GlcCer must be characterized in conditions that are prohibitive to the growth of Δgcs1 (neutral pH and high CO2). These prohibitive conditions are physiologically similar to those found in the extracellular spaces of the lung during infection. Here, using immunofluorescence, we have shown that GlcCer localization to the cell surface is significantly increased during growth in these conditions and during infection. We further seek to exploit this localization by treatment with Cerezyme (Cz), a recombinant enzyme that metabolizes GlcCer, as a potential treatment for Cn. Cz treatment was found to reduce the amount of GlcCer in vitro, in cultures, and in Cn cells inhabiting the mouse lung. Treatment with Cz induced a membrane integrity defect in wild type Cn cells similar to Δgcs1. Cz treatment also reduced the in vitro growth of Cn in a dose and condition dependent manner. Finally, Cz treatment was shown to have a protective effect on survival in mice infected with Cn. Taken together, these studies have established the legitimacy of targeting the GlcCer and other related sphingolipid systems in the development of novel therapeutics

Low-Pathogenic Avian Influenza Viruses in Wild House Mice

Background: Avian influenza viruses are known to productively infect a number of mammal species, several of which are commonly found on or near poultry and gamebird farms. While control of rodent species is often used to limit avian influenza virus transmission within and among outbreak sites, few studies have investigated the potential role of these species in outbreak dynamics. Methodology/Principal Findings: We trapped and sampled synanthropic mammals on a gamebird farm in Idaho, USA that had recently experienced a low pathogenic avian influenza outbreak. Six of six house mice (Mus musculus) caught on the outbreak farm were presumptively positive for antibodies to type A influenza. Consequently, we experimentally infected groups of naïve wild-caught house mice with five different low pathogenic avian influenza viruses that included three viruses derived from wild birds and two viruses derived from chickens. Virus replication was efficient in house mice inoculated with viruses derived from wild birds and more moderate for chicken-derived viruses. Mean titers (EID50 equivalents/mL) across all lung samples from seven days of sampling (three mice/day) ranged from 103.89 (H3N6) to 105.06 (H4N6) for the wild bird viruses and 102.08 (H6N2) to 102.85 (H4N8) for the chicken-derived viruses. Interestingly, multiple regression models indicated differential replication between sexes, with significantly (p\u3c0.05) higher concentrations of avian influenza RNA found in females compared with males. Conclusions/Significance: Avian influenza viruses replicated efficiently in wild-caught house mice without adaptation, indicating mice may be a risk pathway for movement of avian influenza viruses on poultry and gamebird farms. Differential virus replication between males and females warrants further investigation to determine the generality of this result in avian influenza disease dynamics

Cholinergic Activation of M2 Receptors Leads to Context-Dependent Modulation of Feedforward Inhibition in the Visual Thalamus

The temporal dynamics of inhibition within a neural network is a crucial determinant of information processing. Here, the authors describe in the visual thalamus how neuromodulation governs the magnitude and time course of inhibition in an input-dependent way