Catheter-related bacteremia due to Kocuria rosea in a patient undergoing peripheral blood stem cell transplantation

BACKGROUND: Micrococcus species may cause intracranial abscesses, meningitis, pneumonia, and septic arthritis in immunosuppressed or immunocompetent hosts. In addition, strains identified as Micrococcus spp. have been reported recently in infections associated with indwelling intravenous lines, continuous ambulatory peritoneal dialysis fluids, ventricular shunts and prosthetic valves. CASE PRESENTATION: We report on the first case of a catheter-related bacteremia caused by Kocuria rosea, a gram-positive microorganism belonging to the family Micrococcaceae, in a 39-year-old man undergoing peripheral blood stem cell transplantation due to relapsed Hodgkin disease. This uncommon pathogen may cause opportunistic infections in immunocompromised patients. CONCLUSIONS: This report presents a case of Kocuria rosea catheter related bacteremia after stem cell transplantation successfully treated with vancomycin and by catheter removal

Identification of Synaptic Targets of Drosophila Pumilio

Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3′UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3′UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage

Anhydrobiosis and Freezing-Tolerance:Adaptations That Facilitate the Establishment of Panagrolaimus Nematodes in Polar Habitats

<div><p>Anhydrobiotic animals can survive the loss of both free and bound water from their cells. While in this state they are also resistant to freezing. This physiology adapts anhydrobiotes to harsh environments and it aids their dispersal. <i>Panagrolaimus davidi</i>, a bacterial feeding anhydrobiotic nematode isolated from Ross Island Antarctica, can survive intracellular ice formation when fully hydrated. A capacity to survive freezing while fully hydrated has also been observed in some other Antarctic nematodes. We experimentally determined the anhydrobiotic and freezing-tolerance phenotypes of 24 <i>Panagrolaimus</i> strains from tropical, temperate, continental and polar habitats and we analysed their phylogenetic relationships. We found that several other <i>Panagrolaimus</i> isolates can also survive freezing when fully hydrated and that tissue extracts from these freezing-tolerant nematodes can inhibit the growth of ice crystals. We show that <i>P. davidi</i> belongs to a clade of anhydrobiotic and freezing-tolerant panagrolaimids containing strains from temperate and continental regions and that <i>P. superbus</i>, an early colonizer at Surtsey island, Iceland after its volcanic formation, is closely related to a species from Pennsylvania, USA. Ancestral state reconstructions show that anhydrobiosis evolved deep in the phylogeny of <i>Panagrolaimus</i>. The early-diverging <i>Panagrolaimus</i> lineages are strongly anhydrobiotic but weakly freezing-tolerant, suggesting that freezing tolerance is most likely a derived trait. The common ancestors of the <i>davidi</i> and the <i>superbus</i> clades were anhydrobiotic and also possessed robust freezing tolerance, along with a capacity to inhibit the growth and recrystallization of ice crystals. Unlike other endemic Antarctic nematodes, the life history traits of <i>P. davidi</i> do not show evidence of an evolved response to polar conditions. Thus we suggest that the colonization of Antarctica by <i>P. davidi</i> and of Surtsey by <i>P. superbus</i> may be examples of recent “ecological fitting” of freezing-tolerant anhydrobiotic propagules to the respective abiotic conditions in Ross Island and Surtsey.</p></div

Evaluating digital diabetic retinopathy screening in people aged 90 years and over

To evaluate the effectiveness of digital diabetic retinopathy screening in patients aged 90 years and over.MethodsThis is a retrospective analysis of 200 randomly selected patients eligible for diabetic retinopathy screening aged 90 years and over within the Birmingham, Solihull, and Black Country Screening Programme.ResultsOne hundred and seventy-nine (90%) patients attended screening at least once. 133 (74%) annual screening after their first screen, of whom 59% had no detectable diabetic retinopathy; 38 (21%) were referred for ophthalmology clinical assessment-36 for nondiabetic retinopathy reasons and two for diabetic maculopathy. Cataract accounted for 50% of all referrals for ophthalmology clinical assessment. Of the 133 patients placed on annual screening, 93 (70%) were screened at least once more. In terms of level of diabetic retinopathy, assessability or other ocular pathologies, 8 improved, 51 remained stable, and 31 deteriorated. Of the latter, 19 patients were referred for ophthalmology clinical assessment; none of these for diabetic retinopathy.ConclusionsScreening provides opportunistic identification of important nondiabetic retinopathy eye conditions. However, in view of the low identification rate of sight-threatening diabetic retinopathy in patients aged 90 years and over, and the current mission statement of the NHS Diabetic Eye Screening Programme, systematic annual diabetic retinopathy screening may not be justified in this age group of patients, but rather be performed in optometric practice

Identification of Synaptic Targets of Drosophila Pumilio

Drosophila Pumilio (Pum) protein is a translational regulator involved in embryonic patterning and germline development. Recent findings demonstrate that Pum also plays an important role in the nervous system, both at the neuromuscular junction (NMJ) and in long-term memory formation. In neurons, Pum appears to play a role in homeostatic control of excitability via down regulation of para, a voltage gated sodium channel, and may more generally modulate local protein synthesis in neurons via translational repression of eIF-4E. Aside from these, the biologically relevant targets of Pum in the nervous system remain largely unknown. We hypothesized that Pum might play a role in regulating the local translation underlying synapse-specific modifications during memory formation. To identify relevant translational targets, we used an informatics approach to predict Pum targets among mRNAs whose products have synaptic localization. We then used both in vitro binding and two in vivo assays to functionally confirm the fidelity of this informatics screening method. We find that Pum strongly and specifically binds to RNA sequences in the 3′UTR of four of the predicted target genes, demonstrating the validity of our method. We then demonstrate that one of these predicted target sequences, in the 3′UTR of discs large (dlg1), the Drosophila PSD95 ortholog, can functionally substitute for a canonical NRE (Nanos response element) in vivo in a heterologous functional assay. Finally, we show that the endogenous dlg1 mRNA can be regulated by Pumilio in a neuronal context, the adult mushroom bodies (MB), which is an anatomical site of memory storage

BicaudalD Actively Regulates Microtubule Motor Activity in Lipid Droplet Transport

A great deal of sub-cellular organelle positioning, and essentially all minus-ended organelle transport, depends on cytoplasmic dynein, but how dynein's function is regulated is not well understood. BicD is established to play a critical role in mediating dynein function-loss of BicD results in improperly localized nuclei, mRNA particles, and a dispersed Golgi apparatus-however exactly what BicD's role is remains unknown. Nonetheless, it is widely believed that BicD may act to tether dynein to cargos. Here we use a combination of biophysical and biochemical studies to investigate BicD's role in lipid droplet transport during Drosophila embryogenesis.Functional loss of BicD impairs the embryo's ability to control the net direction of droplet transport; the developmentally controlled reversal in transport is eliminated. We find that minimal BicD expression (near-BicD(null)) decreases the average run length of both plus and minus end directed microtubule (MT) based transport. A point mutation affecting the BicD N-terminus has very similar effects on transport during cellularization (phase II), but in phase III (gastrulation) motion actually appears better than in the wild-type.In contrast to a simple static tethering model of BicD function, or a role only in initial dynein recruitment to the cargo, our data uncovers a new dynamic role for BicD in actively regulating transport. Lipid droplets move bi-directionally, and our investigations demonstrate that BicD plays a critical-and temporally changing-role in balancing the relative contributions of plus-end and minus-end motors to control the net direction of transport. Our results suggest that while BicD might contribute to recruitment of dynein to the cargo it is not absolutely required for such dynein localization, and it clearly contributes to regulation, helping activation/inactivation of the motors

Role of Mitochondrial Electron Transport Chain Complexes in Capsaicin Mediated Oxidative Stress Leading to Apoptosis in Pancreatic Cancer Cells

We evaluated the mechanism of capsaicin-mediated ROS generation in pancreatic cancer cells. The generation of ROS was about 4–6 fold more as compared to control and as early as 1 h after capsaicin treatment in BxPC-3 and AsPC-1 cells but not in normal HPDE-6 cells. The generation of ROS was inhibited by catalase and EUK-134. To delineate the mechanism of ROS generation, enzymatic activities of mitochondrial complex-I and complex-III were determined in the pure mitochondria. Our results shows that capsaicin inhibits about 2.5–9% and 5–20% of complex-I activity and 8–75% of complex-III activity in BxPC-3 and AsPC-1 cells respectively, which was attenuable by SOD, catalase and EUK-134. On the other hand, capsaicin treatment failed to inhibit complex-I or complex-III activities in normal HPDE-6 cells. The ATP levels were drastically suppressed by capsaicin treatment in both BxPC-3 and AsPC-1 cells and attenuated by catalase or EUK-134. Oxidation of mitochondria-specific cardiolipin was substantially higher in capsaicin treated cells. BxPC-3 derived ρ0 cells, which lack mitochondrial DNA, were completely resistant to capsaicin mediated ROS generation and apoptosis. Our results reveal that the release of cytochrome c and cleavage of both caspase-9 and caspase-3 due to disruption of mitochondrial membrane potential were significantly blocked by catalase and EUK-134 in BxPC-3 cells. Our results further demonstrate that capsaicin treatment not only inhibit the enzymatic activity and expression of SOD, catalase and glutathione peroxidase but also reduce glutathione level. Over-expression of catalase by transient transfection protected the cells from capsaicin-mediated ROS generation and apoptosis. Furthermore, tumors from mice orally fed with 2.5 mg/kg capsaicin show decreased SOD activity and an increase in GSSG/GSH levels as compared to controls. Taken together, our results suggest the involvement of mitochondrial complex-I and III in capsaicin-mediated ROS generation and decrease in antioxidant levels resulting in severe mitochondrial damage leading to apoptosis in pancreatic cancer cells

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

A randomized clinical trial comparing hydrocolloid, phenytoin and simple dressings for the treatment of pressure ulcers [ISRCTN33429693]

BACKGROUND: Pressure sores are important and common complications of spinal cord injury. Many preventive and therapeutic approaches have been tried and new trials are evolving. One relatively recent method is application of a hydrocolloid dressing (HD). In this study we compared the therapeutic effects of HD on pressure ulcer healing with two other topical applications, phenytoin cream (PC) and simple dressing (SD). METHODS: Ninety-one stage I and stage II pressure ulcers of 83 paraplegic male victims of the Iran-Iraq war were randomly allocated to three treatment groups. Mean age and weight of the participants were 36.64 ± 6.04 years and 61.12 ± 5.08 kg, respectively. All the patients were managed in long term care units or in their homes for 8 weeks by a team of general practitioners and nurses, and the ulcer status was recorded as "Complete healing", "Partial healing", "Without improvement" and "Worsening". RESULTS: Complete healing of ulcers, regardless of location and stage, was better in the HD group than the PC [23/31(74.19%) vs 12/30(40%); difference: 34.19%, 95% CI = 10.85–57.52, (P < 0.01)] or the SD [23/31(74.19%) vs 8/30(26.66%); difference: 47.53%, 95% CI = 25.45–69.61, (P < 0.005)] groups. Complete healing of stage I ulcers in the HD group [11/13(85%)] was better than in the SD [5/11(45%); difference: 40%, 95% CI = 4.7–75.22, (P < 0.05)] or PC [2/9 (22%); difference: 63%, 95% CI = 29.69–96.3, (P < 0.005)] groups. Complete healing of stage II ulcer in the HD group [12/18 (67%)] was better than in the SD group [3/19(16%); difference: 51%, 95% CI = 23.73–78.26, (P < 0.005)], but not significantly different from the PC group [10/21 (48%); difference: 19%, 95% CI = -11.47–49.47, (P > 0.05)]. We performed a second analysis considering only one ulcer per patient (i.e. 83 ulcers in 83 patients). This "per patient" analysis showed that complete ulcer healing in the HD group was better than in the PC [20/28(71.4%) vs 11/28 (39.3%); difference: 32.1%, 95% CI = 7.4–56.7, (P < 0.01)] or SD [20/28(71.4%) vs 8/27 (29.6%); difference: 41.8%, 95% CI = 17.7–65.8, (P < 0.005)] groups. CONCLUSION: We deduced that HD is the most effective method investigated for treating stage I and II pressure ulcers in young paraplegic men

Negative Regulation of EGFR/MAPK Pathway by Pumilio in Drosophila melanogaster

In Drosophila melanogaster, specification of wing vein cells and sensory organ precursor (SOP) cells, which later give rise to a bristle, requires EGFR signaling. Here, we show that Pumilio (Pum), an RNA-binding translational repressor, negatively regulates EGFR signaling in wing vein and bristle development. We observed that loss of Pum function yielded extra wing veins and additional bristles. Conversely, overexpression of Pum eliminated wing veins and bristles. Heterozygotes for Pum produced no phenotype on their own, but greatly enhanced phenotypes caused by the enhancement of EGFR signaling. Conversely, over-expression of Pum suppressed the effects of ectopic EGFR signaling. Components of the EGFR signaling pathway are encoded by mRNAs that have Nanos Response Element (NRE)–like sequences in their 3’UTRs; NREs are known to bind Pum to confer regulation in other mRNAs. We show that these NRE-like sequences bind Pum and confer repression on a luciferase reporter in heterologous cells. Taken together, our evidence suggests that Pum functions as a negative regulator of EGFR signaling by directly targeting components of the pathway in Drosophila