Purpura Fulminans Secondary to Serratia Marcescens Septicemia

A 35-year-old woman developed Serratia marcescens septicemia and purpura fulminans with evidence of disseminated intravascular coagulation. She was successfully treated with heparin sodium and antibiotics

Properties of Normal Rat Kidney Cells Transformed by a Temperature-Sensitive Mutant (LA31) of Rous Sarcoma Virus

The basis of this investigation is to characterize growth property differences in normal versus virally transformed cells. Using a temperature-sensitive mutant of Rous sarcoma virus, the cells' transformation state is regulated by the growth temperature; at 33°C the cells are transformed, while at 39°C the cells have normal characteristics. The morphology of NRK cells is elongated and fibroblastic; when transformed the cells are rounded. Normal cells grow to a monolayer and stop, while transformed cells grow to saturation densities greater than just a monolayer amount. Transformed cells can form foci when grown in mixture with normal cells. Normal cells must be in contact with the culture vessel in order to grow, but transformed cells lack anchorage dependence for growth

Effect of an agri-environmental measure on nitrate leaching from a beef farming system in Ireland

peer-reviewedAgricultural nitrogen (N) management remains a key environmental challenge. Improving N management is a matter of urgency to reduce the serious ecological consequences of the reactive N. Nitrate (NO3−–N) leaching was measured under suckler beef production systems stocked at two intensities: (1) intensive, 210 kg organic N ha−1 with two cut silage harvests; and (2) rural environmental protection scheme (REPS), 170 kg organic N ha−1 with one cut silage harvest. Three replicate plots of each treatment were instrumented with ceramic cups (8 per plot), randomly placed within each plot at a depth of 1 m to collect soil solution for NO3−–N at 50 kPa suction to collecting vessels one week prior to sampling. Samples were taken on a total of 53 sampling dates over 3 winter drainage periods (2002/03, 2003/04 and 2004/05). Over the course of the experiment the mean annual soil solution NO3−–N concentration exceeded the MAC twice out of 15 means (5 treatments over 3 years). The REPS grazing and silage sub treatments had significantly lower mean annual soil solution total oxidized N (TON) concentrations than the respective intensive treatments in years 2 and 3. Annual total NO3−–N losses over the three years in intensive and REPS systems ranged from 55 to 71 and 15 to 20 kg N ha−1, respectively. Mean N surpluses in intensive and REPS systems were 210 and 95 kg ha−1, respectively with the corresponding mean N inputs of 272 and 124 kg N ha−1. The reduction in N inputs under the REPS system results in lower N leaching losses and contributed to a significant reduction in pressures on water quality

PMP22 exon 4 deletion causes ER retention of PMP22 and a gain-of-function allele in CMT1E

OBJECTIVE: To determine whether predicted fork stalling and template switching (FoSTeS) during mitosis deletes exon 4 in peripheral myelin protein 22 KD (PMP22) and causes gain‐of‐function mutation associated with peripheral neuropathy in a family with Charcot–Marie–Tooth disease type 1E. METHODS: Two siblings previously reported to have genomic rearrangements predicted to involve exon 4 of PMP22 were evaluated clinically and by electrophysiology. Skin biopsies from the proband were studied by RT‐PCR to determine the effects of the exon 4 rearrangements on exon 4 mRNA expression in myelinating Schwann cells. Transient transfection studies with wild‐type and mutant PMP22 were performed in Cos7 and RT4 cells to determine the fate of the resultant mutant protein. RESULTS: Both affected siblings had a sensorimotor dysmyelinating neuropathy with severely slow nerve conduction velocities (<10 m/sec). RT‐PCR studies of Schwann cell RNA from one of the siblings demonstrated a complete in‐frame deletion of PMP22 exon 4 (PMP22Δ4). Transfection studies demonstrated that PMP22Δ4 protein is retained within the endoplasmic reticulum and not transported to the plasma membrane. CONCLUSIONS: Our results confirm that that FoSTeS‐mediated genomic rearrangement produced a deletion of exon 4 of PMP22, resulting in expression of both PMP22 mRNA and protein lacking this sequence. In addition, we provide experimental evidence for endoplasmic reticulum retention of the mutant protein suggesting a gain‐of‐function mutational mechanism consistent with the observed CMT1E in this family. PMP22Δ4 is another example of a mutated myelin protein that is misfolded and contributes to the pathogenesis of the neuropathy

Large spin relaxation rates in trapped submerged-shell atoms

Spin relaxation due to atom-atom collisions is measured for magnetically trapped erbium and thulium atoms at a temperature near 500 mK. The rate constants for Er-Er and Tm-Tm collisions are 3.0 times 10^-10 cm^3 s^-1 and 1.1 times 10^-10 cm^3 s^-1, respectively, 2-3 orders of magnitude larger than those observed for highly magnetic S-state atoms. This is strong evidence for an additional, dominant, spin relaxation mechanism, electrostatic anisotropy, in collisions between these "submerged-shell" L > 0 atoms. These large spin relaxation rates imply that evaporative cooling of these atoms in a magnetic trap will be highly inefficient.Comment: 10 pages, 3 figure

Treatment algorithm for infants diagnosed with spinal muscular atrophy through newborn screening

Spinal muscular atrophy (SMA) is an autosomal recessive disease characterized by the degeneration of alpha motor neurons in the spinal cord, leading to muscular atrophy. SMA is caused by deletions or mutations in the survival motor neuron 1 gene (SMN1). In humans, a nearly identical copy gene, SMN2, is present. Because SMN2 has been shown to decrease disease severity in a dose-dependent manner, SMN2 copy number is predictive of disease severity. To develop a treatment algorithm for SMA-positive infants identified through newborn screening based upon SMN2 copy number. A working group comprised of 15 SMA experts participated in a modified Delphi process, moderated by a neutral third-party expert, to develop treatment guidelines. The overarching recommendation is that all infants with two or three copies of SMN2 should receive immediate treatment (n = 13). For those infants in which immediate treatment is not recommended, guidelines were developed that outline the timing and appropriate screens and tests to be used to determine the timing of treatment initiation. The identification SMA affected infants via newborn screening presents an unprecedented opportunity for achievement of maximal therapeutic benefit through the administration of treatment pre-symptomatically. The recommendations provided here are intended to help formulate treatment guidelines for infants who test positive during the newborn screening process

Clinical Impact of Chronic Venous Changes Induced by Central Lines in Children: A Cohort with Abnormal Venograms

PURPOSE To explore the hypothesis that central venous stenosis/obstructions (CVS/O) in children are influenced by prior central venous access devices (CVADs) and are associated with future risk for thromboses. MATERIAL AND METHODS A convenience sample of 100 patients with abnormal venography (stenosis, collaterals, occlusions) documented during peripherally inserted central catheter (PICC) placements were identified from consecutive PICC placements (January 2008 to November 2012). The patients (41 males, 59 females, median age 2.7 years, median weight 11 kg) were categorized based on venographic presence (Group A, n = 53) or absence (Group B, n = 47) of visible connection to the superior vena cava. Each patient's CVAD history, before and after venography, was analyzed (until October 2016). RESULTS Before venogram, Group B patients were associated with a higher number of previous CVADs, larger diameter devices, greater incidence of malposition, and more use of polyurethane catheters than Group A patients (P < .001). An ipsilateral PICC was successfully placed in 98% of Group A, compared to 32% of Group B (P < .001). After venogram, significantly more Doppler ultrasounds (DUS) were performed and thromboses diagnosed in Group B (57% and 36%) compared to Group A (21% and 8%) (P < .003; P = .001), respectively. CONCLUSIONS Previous catheter characteristics influenced the severity of venographic changes of CVS/O (Group B). Group B was associated with more subsequent symptomatic thromboses. This information may assist parents and referring physicians to anticipate potential adverse sequelae from CVS/O on the child's venous health

The identification of Staphylococcus aureus factors required for pathogenicity and growth in human blood

Staphylococcus aureus is a human commensal but also has devastating potential as an opportunist pathogen. S. aureus bacteraemia is often associated with an adverse outcome. To identify potential targets for novel control approaches we have identified S. aureus components that are required for growth on human blood. An ordered transposon mutant library was screened, identifying 9 genes involved specifically in haemolysis or growth on human blood agar compared to the parental strain. Three genes (purA, purB and pabA) were subsequently found to be required for pathogenesis in the zebrafish embryo infection model. The pabA growth defect was specific to the red blood cell component of human blood, showing no growth difference compared to the parental strain on human serum, human plasma, sheep or horse blood. PabA is required in the tetrahydrofolate (THF) biosynthesis pathway. The pabA growth defect was found to be due to a combination of loss of THF-dependent dTMP production by the enzyme ThyA and an increased demand for pyrimidines in human blood. Our work highlights pabA and the pyrimidine salvage pathway as potential targets for novel therapeutics and suggests a previously undefined role for a human blood factor in the activity of sulphonamide antibiotics