Surface Microbiology of the iPad Tablet Computer and the Potential to Serve as a Fomite in Both Inpatient Practice Settings as Well as Outside of the Hospital Environment

Background

The use of tablet computers and other touch screen technology within the healthcare system has rapidly expanded. It has been reported that these devices can harbor pathogens in hospitals; however, much less is known about what pathogens they can harbor when used outside the hospital environment compared to hospital practice.

Methods

Thirty iPads belonging to faculty with a variety of practice settings were sampled to determine the presence and quantity of clinically-relevant organisms. Flocked nylon swabs and neutralizer solution were used to sample the surface of each iPad. Samples were then plated on a variety of selective agars for presence and quantity of selected pathogens. In addition, faculty members were surveyed to classify the physical location of their practice settings and usage patterns. Continuous variables were compared via an unpaired Student''s t test with two-tailed distribution; categorical variables were compared with the Fisher''s exact test.

Results

Of the iPads sampled, 16 belonged to faculty practicing within a hospital and 14 belonged to a faculty member practicing outside a hospital. More faculty within the hospital group used their iPads at their practice sites (78.6% vs. 31.3%; p = 0.014) and within patient care areas (71.4% vs. 18.8%; p = 0.009) than the non-hospital group. There were no differences in the presence, absence, or quantity of, any of the pathogens selectively isolated between groups. Problematic nosocomial pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and P. aeruginosa were isolated from both hospital and non-hospital faculty iPads.

Conclusions

Gram positive and Gram negative organisms were recovered from the surfaces of iPads regardless of practice setting; these included problematic multidrug-resistant pathogens like MRSA, VRE, and Pseudomonas aeruginosa. Healthcare personnel in all settings should be aware of the potential for tablet computers to serve as a nidus for microorganism transmission.     

Defective Wnt-dependent cerebellar midline fusion in a mouse model of Joubert syndrome

The ciliopathy Joubert syndrome is marked by cerebellar vermis hypoplasia, a phenotype for which the pathogenic mechanism is unclear. To investigate Joubert syndrome pathogenesis, we have examined mice with mutated Ahi1, the first identified Joubert syndrome-associated gene. These mice show cerebellar hypoplasia with a vermis-midline fusion defect early in development. This defect is concomitant with expansion of the roof plate and is also evident in a mouse mutant for another Joubert syndrome-associated gene, Cep290. Furthermore, fetal magnetic resonance imaging (MRI) of human subjects with Joubert syndrome reveals a similar midline cleft, suggesting parallel pathogenic mechanisms. Previous evidence has suggested a role for Jouberin (Jbn), the protein encoded by Ahi1, in canonical Wnt signaling. Consistent with this, we found decreased Wnt reporter activity at the site of hemisphere fusion in the developing cerebellum of Ahi1-mutant mice. This decrease was accompanied by reduced proliferation at the site of fusion. Finally, treatment with lithium, a Wnt pathway agonist, partially rescued this phenotype. Our findings implicate a defect in Wnt signaling in the cerebellar midline phenotype seen in Joubert syndrome that can be overcome with Wnt stimulation.     

Subcellular spatial regulation of canonical Wnt signalling at the primary cilium

Mechanisms of signal transduction regulation remain a fundamental question in a variety of biological processes and diseases. Previous evidence indicates that the primary cilium can act as a signalling hub, but its exact role in many of the described pathways has remained elusive. Here, we investigate the mechanism of cilia-mediated regulation of the canonical Wnt pathway. We found that primary cilia dampen canonical Wnt signalling through a spatial mechanism involving compartmentalization of signalling components. The cilium, through regulated intraflagellar transport, diverts Jouberin (Jbn), a ciliopathy protein and context-specific Wnt pathway regulator, away from the nucleus and limits β-catenin nuclear entry. This repressive regulation does not silence the pathway, but instead maintains a discrete range of Wnt responsiveness; cells without cilia have potentiated Wnt responses, whereas cells with multiple cilia have inhibited responses. Furthermore, we show that this regulation occurs during embryonic development and is disrupted in cancer cell proliferation. Together these data explain a spatial mechanism of Wnt signalling regulation that may provide insight into ciliary regulation of other signalling pathways.     

Outcomes of multi-drug resistant tuberculosis (MDR-TB) among a cohort of South African patients with high HIV prevalence

Background

Multidrug-resistant tuberculosis (MDR-TB) is a major clinical challenge, particularly in patients with human immunodeficiency virus (HIV) co-infection. MDR-TB treatment is increasingly available, but outcomes have not been well characterized. South Africa has provided MDR-TB treatment for a decade, and we evaluated outcomes by HIV status for patients enrolled between 2000 and 2004 prior to anti-retroviral access.

Methods

We assessed treatment outcomes in a prospective cohort of patients with MDR-TB from eight provincial programs providing second line drugs. World Health Organization definitions were used. Results were stratified by HIV status.

Results

Seven hundred fifty seven patients with known HIV status were included in the final analysis, and HIV infection was documented in 287 (38%). Overall, 348 patients (46.0%) were successfully treated, 74 (9.8%) failed therapy, 177 (23.4%) died and 158 (20.9%) defaulted. Patients with HIV were slightly younger and less likely to be male compared to HIV negative patients. Patients with HIV were less likely to have a successful treatment outcome (40.0 vs. 49.6; P<0.05) and more likely to die (35.2 vs. 16.2; P<0.0001). In a competing risk survival analysis, patients with HIV had a higher hazard of death (HR: 2.33, P<0.0001). Low baseline weight (less than 45 kg and less than 60 kg) was also associated with a higher hazard of death (HR: 2.52, P<0.0001; and HR: 1.50, P<0.0001, respectively, compared to weight greater than 60 kg). Weight less than 45 kg had higher risk of failure (HR: 3.58, P<0.01). Any change in treatment regimen was associated with a higher hazard of default (HR: 2.86; 95% CI 1.55–5.29, P<0.001) and a lower hazard of death (HR: 0.63, P<0.05).

Conclusions

In this MDR-TB treatment program patients with HIV infection and low weight had higher hazards of death. Overall treatment outcomes were poor. Efforts to improve treatment for MDR-TB are urgently needed.     

The influence of water level on macrophyte growth and trophic interactions in eutrophic Mediterranean shallow lakes: a mesocosm experiment with and without fish

1. Water‐level fluctuations are typical of lakes located in the semi‐arid Mediterranean region, which is characterised by warm rainy winters and hot dry summers. Ongoing climate change may exacerbate fluctuations and lead to more severe episodes of drought, so information on the effects of water level on the functioning of lake ecosystems in such regions is crucial. 2. In eutrophic Lake Eymir, Turkey, we conducted a 4‐month (summer) field experiment using cylindrical 0.8‐m‐ (low‐water‐level) and 1.6‐m‐deep (high‐water‐level) mesocosms (kept open to the sediment and atmosphere). Fish (tench, Tinca tinca, and bleak, Alburnus escherichii) were added to half of the mesocosms, while the rest were kept fishless. Ten shoots of Potamogeton pectinatus were transplanted to each mesocosm. 3. Sampling for physicochemical variables, chlorophyll a (chl‐a), zooplankton and per cent plant volume inhabited (PVI%) by macrophytes was conducted weekly during the first 5 weeks, and subsequently biweekly. Macrophytes were harvested on the last sampling date. During the course of the experiment, the water level decreased by 0.41 ± 0.06 m. 4. Throughout the experiment, fish affected zooplankton abundance (?), nutrient concentrations (+), chl‐a (+) and water clarity (?) most strongly in the low‐water‐level mesocosms and the zooplankton community shifted towards dominance of small‐sized forms. The fishless mesocosms had a higher zooplankton/phytoplankton ratio, suggesting higher grazing. 5. Greatest macrophyte growth was observed in the low‐water‐level fishless mesocosms. However, despite high nutrient concentrations and low water clarity, macrophytes were also abundant in the fish mesocosms and particularly increased following a water‐level decrease from midsummer onwards. Macrophyte growth was poor in the high‐water‐level mesocosms, even in the fishless ones with high water clarity. This was ascribed to extensive periphyton development reducing light availability for the macrophytes. 6. Our results indicate that a reduction in water level during summer may help maintain the growth of macrophytes in Mediterranean eutrophic shallow lakes, despite a strong negative effect of fish predation on water clarity. It is therefore probable that an expected negative effect of global climate change on water clarity because of eutrophication and enhanced top‐down control of fish may be, at least partly, counteracted by reduced water level, provided that physical disturbance is not severe.     

COMT val158met predicts reward responsiveness in humans

A functional variant of the catechol‐O‐methyltransferase (COMT) gene [val158met (rs4680)] is frequently implicated in decision‐making and higher cognitive functions. It may achieve its effects by modulating dopamine‐related decision‐making and reward‐guided behaviour. Here we demonstrate that individuals with the met/met polymorphism have greater responsiveness to reward than carriers of the val allele and that this correlates with risk‐seeking behaviour. We assessed performance on a reward responsiveness task and the Balloon analogue risk task, which measure how participants (N = 70, western European, university and postgraduate students) respond to reward and take risks in the presence of available reward. Individuals with the met/met genotype (n = 19) showed significantly higher reward responsiveness, F_2,64 = 4.02, P = 0.02, and reward‐seeking behaviour, F(2,68) = 4.52, P = 0.01, than did either val/met (n = 25) or val/val (n = 26) carriers. These results highlight a scenario in which genotype‐dependent reward responsiveness shapes reward‐seeking, therefore suggesting a novel framework by which COMT may modulate behaviour.     

A mechanistic basis for amplification differences between samples and between genome regions

ABSTRACT: BACKGROUND: For many analytical methods the efficiency of DNA amplification varies across the genome and between samples. The most affected genome regions tend to correlate with high C + G content, however this relationship is complex and does not explain why the direction and magnitude of effects varies considerably between samples. RESULTS: Here, we provide evidence that sequence elements that are particularly high in C + G content can remain annealed even when aggressive melting conditions are applied. In turn, this behavior creates broader 'Thermodynamically Ultra-Fastened' (TUF) regions characterized by incomplete denaturation of the two DNA strands, so reducing amplification efficiency throughout these domains. CONCLUSIONS: This model provides a mechanistic explanation for why some genome regions are particularly difficult to amplify and assay in many procedures, and importantly it also explains inter-sample variability of this behavior. That is, DNA samples of varying quality will carry more or fewer nicks and breaks, and hence their intact TUF regions will have different lengths and so be differentially affected by this amplification suppression mechanism -- with 'higher' quality DNAs being the most vulnerable. A major practical consequence of this is that inter-region and inter-sample variability can be largely overcome by employing routine fragmentation methods (e.g. sonication or restriction enzyme digestion) prior to sample amplification.     

Nifedipine loaded chitosan microspheres prepared by emulsification phase-separation

A high yield of nifedipine-chitosan microspheres could be obtained using an emulsification phase-separation method. A high level of entrapment of nifedipine in the microspheres was achieved. The microspheres exhibited excellent swelling properties. Differential scanning calorimetry, X-ray diffractometry, and scanning electron microscopy confirmed that at 1.84% loading, nifedipine was dispersed molecularly. The microspheres exhibited faster release at low loadings compared to high loadings. Fitting the data to the coupled Fickian/case II equation, showed that at low loadings polymer relaxation coefficients (k₂) were high. As the polymer content increased in the microspheres, the value of n (diffusional exponent characteristic of the release mechanism) approached one, which is indicative of zero order.