Stage progression and neurological symptoms in Trypanosoma brucei rhodesiense sleeping sickness: role of the CNS inflammatory response

Background: Human African trypanosomiasis progresses from an early (hemolymphatic) stage, through CNS invasion to the late (meningoencephalitic) stage. In experimental infections disease progression is associated with neuroinflammatory responses and neurological symptoms, but this concept requires evaluation in African trypanosomiasis patients, where correct diagnosis of the disease stage is of critical therapeutic importance. Methodology/Principal Findings: This was a retrospective study on a cohort of 115 T.b.rhodesiense HAT patients recruited in Eastern Uganda. Paired plasma and CSF samples allowed the measurement of peripheral and CNS immunoglobulin and of CSF cytokine synthesis. Cytokine and immunoglobulin expression were evaluated in relation to disease duration, stage progression and neurological symptoms. Neurological symptoms were not related to stage progression (with the exception of moderate coma). Increases in CNS immunoglobulin, IL-10 and TNF-α synthesis were associated with stage progression and were mirrored by a reduction in TGF-β levels in the CSF. There were no significant associations between CNS immunoglobulin and cytokine production and neurological signs of disease with the exception of moderate coma cases. Within the study group we identified diagnostically early stage cases with no CSF pleocytosis but intrathecal immunoglobulin synthesis and diagnostically late stage cases with marginal CSF pleocytosis and no detectable trypanosomes in the CSF. Conclusions: Our results demonstrate that there is not a direct linkage between stage progression, neurological signs of infection and neuroinflammatory responses in rhodesiense HAT. Neurological signs are observed in both early and late stages, and while intrathecal immunoglobulin synthesis is associated with neurological signs, these are also observed in cases lacking a CNS inflammatory response. While there is an increase in inflammatory cytokine production with stage progression, this is paralleled by increases in CSF IL-10. As stage diagnostics, the CSF immunoglobulins and cytokines studied do not have sufficient sensitivity to be of clinical value

Assessment of the variability of airborne contamination levels in an intensive care unit over a 24 hour period

Introduction: The objective of this study was to evaluate the variability in the dynamics and levels of airborne contamination within a hospital ICU in order to establish an improved understanding of the extent to which airborne bioburden contributes to cross-infection of patients. Microorganisms from the respiratory tract or skin can become airborne by coughing, sneezing and periods of increased activity such as bed changes and staff rounds. Current knowledge of the clinical microflora is limited however it is estimated that 10-33% of nosocomial infections are transmitted via air. Methods: Environmental air monitoring was conducted in Glasgow Royal Infirmary ICU, in the open ward and in patient isolation rooms. A sieve impactor air sampler was used to collect 500 L air samples every 15 minutes over 10 hour (08:00-18:00 h) and 24 hour (08:00-08:00 h) periods. Samples were collected, room activity logged and the bacterial contamination levels were recorded as CFU/m3 of air. Results: A high degree of variability in levels of airborne contamination was observed over the course of a 10 hour day and a 24 period in a hospital ICU. Counts ranged from 12-510 CFU/m3 over 24 hours in an isolation room occupied for 10 days by a patient with C. difficile infection. Contamination levels were found to be lowest during the night and in unoccupied rooms, with an average value of 20 CFU/m3. Peaks in airborne contamination showed a direct relation to an increase in room activity. Conclusions: This study demonstrates the degree of airborne contamination that can occur in an ICU over a 24 hour period. Numerous factors were found to contribute to microbial air contamination and consideration should be given to potential improved infection control strategies and decontamination technologies which could be deployed within the clinical environment to reduce the airborne contamination levels, with the ultimate aim of reducing healthcare-associated infections from environmental sources

Evaluation of the airborne contamination levels in an intensive care unit over a 24 hour period

Airborne transmission of infectious microorganisms poses a critical threat to human health, particularly in the clinical setting where it is estimated that 10-33% of nosocomial infections are spread via the air. Within the clinical environment, microorganisms originating from the human respiratory tract or skin can become airborne by coughing and sneezing, and periods of increased activity such as bed and dressing changes, movement, staff rounds and visiting hours. Current knowledge of the clinical airborne microflora is limited and there is uncertainty surrounding the contribution of airborne microorganisms to the transmission of nosocomial infection. This study aims to establish an improved understanding of the variability in the dynamics and levels of airborne microbial contamination within an operational intensive care unit (ICU). Methods Environmental monitoring of airborne contamination levels was conducted in Glasgow Royal Infirmary ICU, in the open ward and in both occupied and unoccupied patient isolation rooms. Monitoring was performed using a sieve impactor air sampler, with 500 L air samples collected every 15 minutes over 10 hour (08:00-18:00 h) and 24 hour (08:00-08:00 h) periods. Samples were collected on tryptone soya agar (TSA) plates, and the bacterial contamination levels were recorded as CFU/m3 of air. An activity log was also collated over the 10 hour and 24 hour sampling periods in order to record any activity occurring in the ward/room that might contribute to spikes in airborne contamination levels. Results Results highlight the degree of variability in levels of airborne contamination over the course of both a working day and a 24 hour period in a hospital ICU. A high degree of variability was observed across the 24 hour period, with counts ranging from 12-510 CFU/m3 in one study in an occupied patient room. Peaks in airborne contamination showed a direct relation to an increase in room activity. Monitoring found contamination levels to be lower overall during the night, and in unoccupied isolation rooms, with an average value of 20 CFU/m3. The highest counts were observed in an isolation room occupied for 10 days by a patient with C. difficile infection which generated an average microbial load of 104 CFU/m3 and a peak value of 510 CFU/m3. Discussion This study has demonstrated the degree of airborne contamination that can occur in the ICU environment over a 24 hour period. Numerous factors were found to contribute to the microbial air contamination levels, including patient status, length of room occupation, time of day and room activity, and further work is required to establish the extent to which this airborne bioburden contributes to cross-infection of patients

Absence of Complex I Is Associated with Diminished Respiratory Chain Function in European Mistletoe

Parasitism is a life history strategy found across all domains of life whereby nutrition is obtained from a host. It is often associated with reductive evolution of the genome, including loss of genes from the organellar genomes [1, 2]. In some unicellular parasites, the mitochondrial genome (mitogenome) has been lost entirely, with far-reaching consequences for the physiology of the organism [3, 4]. Recently, mitogenome sequences of several species of the hemiparasitic plant mistletoe (Viscum sp.) have been reported [5, 6], revealing a striking loss of genes not seen in any other multicellular eukaryotes. In particular, the nad genes encoding subunits of respiratory complex I are all absent and other protein-coding genes are also lost or highly diverged in sequence, raising the question what remains of the respiratory complexes and mitochondrial functions. Here we show that oxidative phosphorylation (OXPHOS) in European mistletoe, Viscum album, is highly diminished. Complex I activity and protein subunits of complex I could not be detected. The levels of complex IV and ATP synthase were at least 5-fold lower than in the non-parasitic model plant Arabidopsis thaliana, whereas alternative dehydrogenases and oxidases were higher in abundance. Carbon flux analysis indicates that cytosolic reactions including glycolysis are greater contributors to ATP synthesis than the mitochondrial tricarboxylic acid (TCA) cycle. Our results describe the extreme adjustments in mitochondrial functions of the first reported multicellular eukaryote without complex I

Spectroscopy of 50^{50}Sc and ab initio calculations of B(M3)B(M3) strengths

The GRIFFIN spectrometer at TRIUMF-ISAC has been used to study excited states and transitions in $^{50}$Sc following the $\beta$-decay of $^{50}$Ca. Branching ratios were determined from the measured $\gamma$-ray intensities, and angular correlations of $\gamma$ rays have been used to firmly assign the spins of excited states. The presence of an isomeric state that decays by an $M3$ transition with a $B(M3)$ strength of 13.6(7)\,W.u. has been confirmed. We compare with the first {\it ab initio} calculations of $B(M3$) strengths in light and medium-mass nuclei from the valence-space in-medium similarity renormalization group approach, using consistently derived effective Hamiltonians and $M3$ operator. The experimental data are well reproduced for isoscalar $M3$ transitions when using bare $g$-factors, but the strength of isovector $M3$ transitions are found to be underestimated by an order of magnitude

Continuous monitoring of aerial bioburden within intensive care isolation rooms and identification of 'high risk' activities

Background: The spread of pathogens via the airborne route is often underestimated and little is known about the extent to which airborne microbial contamination levels vary throughout the day and night in hospital facilities. Aims: This study aims to evaluate variability in airborne contamination levels within ICU isolation rooms over extended time periods to improve understanding of the extent to which ward activities, and consequential increases in airborne bioburden, may contribute to cross-infection of patients. Methods: Environmental air monitoring was conducted within occupied and vacant inpatient isolation rooms. A sieve impactor sampler was used to collect 500 L air samples every 15 minutes over 10-hour (08:00-18:00 h) and 24-hour (08:00-08:00 h) periods. Samples were collected, room activity logged, and the bacterial contamination levels were recorded as cfu/m3 of air. Findings: A high degree of variability in levels of airborne contamination was observed across all scenarios in the studied isolation rooms. Air bioburden increased as room occupancy increased, with air contamination levels highest in rooms occupied for the longest time during the study (10 days) with a mean value of 104.4 cfu/m3 and a range of 12–510 cfu/m3. Counts were lowest in unoccupied rooms, with an average value of 20 cfu/m3 and during the night. Conclusion: Peaks in airborne contamination showed a direct relation to an increase in activity levels. This study provides first clear evidence of the extent of variability in microbial airborne levels over 24-hour periods in ICU isolation rooms and directly correlates microbial load to ward activity

Dynamic changes in lung microRNA profiles during the development of pulmonary hypertension due to chronic hypoxia and monocrotaline

<b>Objective</b>: MicroRNAs (miRNAs) are small noncoding RNAs that have the capacity to control protein production through binding "seed" sequences within a target mRNA. Each miRNA is capable of potentially controlling hundreds of genes. The regulation of miRNAs in the lung during the development of pulmonary arterial hypertension (PAH) is unknown.<p></p> <b>Methods and Results</b>: We screened lung miRNA profiles in a longitudinal and crossover design during the development of PAH caused by chronic hypoxia or monocrotaline in rats. We identified reduced expression of Dicer, involved in miRNA processing, during the onset of PAH after hypoxia. MiR-22, miR-30, and let-7f were downregulated, whereas miR-322 and miR-451 were upregulated significantly during the development of PAH in both models. Differences were observed between monocrotaline and chronic hypoxia. For example, miR-21 and let-7a were significantly reduced only in monocrotaline-treated rats. MiRNAs that were significantly regulated were validated by quantitative polymerase chain reaction. By using in vitro studies, we demonstrated that hypoxia and growth factors implicated in PAH induced similar changes in miRNA expression. Furthermore, we confirmed miR-21 downregulation in human lung tissue and serum from patients with idiopathic PAH.<p></p> <b>Conclusion</b>: Defined miRNAs are regulated during the development of PAH in rats. Therefore, miRNAs may contribute to the pathogenesis of PAH and represent a novel opportunity for therapeutic intervention.<p></p&gt