Type II Cryoglobulinaemia causing Monoclonal Gammopathy of Renal Significance.

A 53 year old female with a background of hypertension, hypothyroidism and Raynaud's was admitted with an acute ischaemic stroke and referred to the renal team after a routine urine dip revealed microscopic haematuria and nephrotic-range proteinuria. Blood tests revealed renal impairment, a monoclonal IgM kappa paraprotein, low complement C4 concentration and a positive rheumatoid factor. Active cryoglobulinaemia was suspected and testing demonstrated type II cryoglobulins secondary to the monoclonal IgM kappa paraprotein. Bone marrow biopsy was normal. Renal biopsy revealed cryoglobulinaemia associated membranoproliferative glomerulonephritis. Treatment with steroids and rituximab improved renal function and proteinuria. This case fits within the evolving spectrum of disorders now termed Monoclonal Gammopathy of Renal Significance and highlights the value of biopsying and treating these patients early.

Adherence to General Medical Council guidance regarding disclosure of alternative treatments during the consent process.

INTRODUCTION: General Medical Council (GMC) guidelines dictate that reasonable alternatives to treatment should be disclosed during the consent process. We aimed to determine whether GMC guidelines on disclosure of alternatives during consent are being followed in a real-world example which is disclosure of non-operative management as an alternative to appendicectomy in uncomplicated paediatric appendicitis. METHODS: We undertook a retrospective single-centre observational study and national consultant specialist paediatric surgeon survey. Two groups of 50 consecutively treated children (<16 years) with acute uncomplicated appendicitis were included in the observational study during two periods. UK-based consultant surgeons who treat appendicitis were included in the national survey. The main outcomes were disclosure and use of non-operative management (NOM) as an alternative to appendicectomy. RESULTS: Overall, in the observational study, NOM was disclosed in 30 (30%) children and 77% (23/30) opted for this treatment method when it was disclosed. There were 83 survey respondents representing all 25 eligible specialist paediatric surgery centres. Ten (12%) consultants reported routinely offering NOM, 39 (47%) offer it in select circumstances, and 34 (41%) never offer NOM. Only 25 (30%) respondents always disclose NOM as an alternative to appendicectomy, whereas 22 (27%) never do. Consultants who never disclose NOM are more likely to prefer appendicectomy over NOM compared with those who always disclose it (p<0.001). CONCLUSION: In this illustrative clinical scenario, observed and reported practice regarding disclosure of alternative treatments during the consent process do not meet GMC guidance. This risks depriving children and caregivers of a choice that they are entitled to.

The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8.

The neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of progressive neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in various tissues. Progressive epilepsy with mental retardation (EPMR, MIM 600143) was recently recognized as a new NCL subtype (CLN8). It is an autosomal recessive disorder characterized by onset of generalized seizures between 5 and 10 years, and subsequent progressive mental retardation. Here we report the positional cloning of a novel gene, CLN8, which is mutated in EPMR. It encodes a putative transmembrane protein. EPMR patients were homozygous for a missense mutation (70C-->G, R24G) that was not found in homozygosity in 433 controls. We also cloned the mouse Cln8 sequence. It displays 82% nucleotide identity with CLN8, conservation of the codon harbouring the human mutation and is localized to the same region as the motor neuron degeneration mouse, mnd, a naturally occurring mouse NCL (ref. 4). In mnd/mnd mice, we identified a homozygous 1-bp insertion (267-268insC, codon 90) predicting a frameshift and a truncated protein. Our data demonstrate that mutations in these orthologous genes underlie NCL phenotypes in human and mouse, and represent the first description of the molecular basis of a naturally occurring animal model for NCL.

The experiences of internationally educated nurses in the southeastern United States of America.

BACKGROUND: US healthcare facilities have addressed nursing shortages in part by recruiting internationally educated nurses (IENs), and studies suggest IENs may make up a significant percentage of the nursing workforce in urban hospitals. Despite the economic recession of 2008-2012, international nurse migration is expected to continue. Little is known about IENs in the southeastern USA, and no studies have compared their perspectives to those of their US counterparts. OBJECTIVE: The purpose of this study was to gain a deeper understanding about the experiences of IENs compared to those of US registered nurses (RNs) practising in two urban hospitals in southeastern USA. METHODS: This study involved two rounds of semi-structured interviews of 82 IENs and US RNs. Interviews focused on themes relating to education, barriers to practice, intent to stay in nursing and IENs' migration experiences. FINDINGS AND DISCUSSION: Most IENs interviewed migrated to the USA after 1990 to join their family and do not plan to return to their home countries to practise. Most IENs initially received their Associate Degree in Nursing; many have obtained their Bachelor of Science in Nursing degree. IENs and newly licensed US RNs faced similar barriers when they began practising in the USA, but IENs faced additional challenges adjusting to the attitudes of US patients, the perceived lack of respect for nurses and delivering total patient care. CONCLUSIONS: IENs would benefit from orientation regarding the cultural differences in the USA. In other ways, their challenges are similar to those of US RNs; policies regarding education, recruitment and retention could target both groups together.

Scope and feasibility of operating on the neonatal intensive care unit: 312 cases in 10 years.

PURPOSE: To report the scope, feasibility and learning experience of operating on neonates on the neonatal intensive care unit (NICU). METHODS: (1) Review of all NICU operations performed by general neonatal surgeons over 10 years; (2) 6-month prospective comparison of procedures performed in NICU or operating room; (3) structured interviews with five surgeons with 1-13 years experience of operating on NICU. RESULTS: 312 operations were performed in 249 infants. Median birth weight was 1,494 g (range 415-4,365), gestational age 29 weeks (22-42), and age at operation 25 days (0-163). Nearly half (147) were laparotomy for acute abdominal pathology in preterm, very low birth-weight infants There were no surgical adverse events related to location of surgery. Surgeon satisfaction with operating on NICU for this population was high (5/5). Several factors contribute to making this process a success. CONCLUSIONS: This is the largest reported series of general neonatal surgical procedures performed on NICU. Operating on NICU is feasible and safe, and a full range of neonatal operations can be performed. It removes risks associated with neonatal transfer and is likely to reduce physiological instability. We recommend this approach for all ventilated neonates and urge neonatal surgeons to operate at the cotside of unstable infants.

Effect of reduced atmospheric pressure on growth and quality of two lettuce cultivars.

Future space missions will likely include plants to provide fresh foods and bioregenerative life support capabilities. Current spacecraft such as the International Space Station (ISS) operate at 1 atm (101 kPa) pressure, but future missions will likely use reduced pressures to minimize gas leakage and facilitate rapid egress (space walks). Plants for these missions must be able to tolerate and grow reliably at these reduced pressures. We grew two lettuce cultivars, 'Flandria' a green bibb-type and 'Outredgeous,' a red, loose-leaf type, under three pressures: 96 kPa (ambient control), 67 kPa (2/3 atm), and 33 kPa (1/3 atm) for 21 days in rockwool using recirculating nutrient film technique hydroponics. Each treatment was repeated three times using a different hypobaric chamber each time. A daily light integral of 17.2 Moles Photosynthetically Active Radiation per day was provided with metal halide lamps set to deliver 300 µmol m-2s -1 photosynthetic photon flux (PPF) for a 16 h photoperiod at 22 °C. Oxygen was maintained at 21 kPa (equal to 21% at 1 atm) and CO2 at 0.12 kPa (equal to 1200 ppm at 1 atm). Leaf area for 'Outredgeous' was reduced 20% and 38% at 67 kPa and 33 kPa respectively; shoot fresh mass was reduced 22% and 41% at 67 kPa and 33 kPa respectively when compared to control plants at 96 kPa. These trends were not statistically significant at P ≥ 0.05. Leaf area for 'Flandria' showed no difference between 96 and 67 kPa but was reduced 31% at 33 kPa; shoot fresh mass was reduced 6% and 27% at 66 kPa and 33 kPa respectively compared to 96 kPa. There were 10% and 25% increases in anthocyanin concentration at 66 kPa and 33 kPa compared to 96 kPa, potentially increasing the bioprotective capacity of the plant. Previous studies with other cultivars of lettuce showed slight change in growth across this range of pressures, suggesting responses may vary among genotypes, hypobaric exposure treatments, and / or environmental conditions. Collectively, the findings suggest further testing is needed to understand the effects of atmospheric pressure on plant growth.

Trans-anastomotic tubes reduce the need for central venous access and parenteral nutrition in infants with congenital duodenal obstruction.

PURPOSE: To determine the effect of trans-anastomotic tube (TAT) feeding on outcome following repair of congenital duodenal obstruction (CDO). METHODS: Retrospective comparative study of all infants with CDO over 10 years. Data are median (range). Mann-Whitney U test and Fisher's exact test were used. RESULTS: Of 55 infants with CDO (48 atresia, 7 stenosis), 17 were managed with a TAT, 38 without. Enteral feeds were commenced earlier in infants with a TAT compared to those without (TAT 2 days post-repair [1-4] vs. no-TAT 3 days post-repair [1-7]; p = 0.006). Infants with a TAT achieved full enteral feeds significantly sooner than those without (TAT 6 days post-repair [2-12] vs. no-TAT 9 days post-repair [3-36]; p = 0.005). Significantly fewer infants in the TAT group required central venous catheter (CVC) placement and parenteral nutrition (PN) than in the no-TAT group (TAT 2/17 vs. no-TAT 28/38, p < 0.0001). There were six CVC-related complications (5 infections, 1 PN extravasation) and four TATs became displaced and were removed before achieving full enteral feeds. One infant with a TAT with trisomy 21 and undiagnosed Hirschsprung disease developed an anastomotic leak and jejunal perforation requiring re-operation. CONCLUSIONS: A TAT significantly shortens time to full enteral feeds in infants with CDO significantly reducing the need for central venous access and PN.

Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells.

T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4(+) cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor-alpha/beta transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-gamma. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-gamma production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention.

Addition of nanoparticle dispersions to enhance flux pinning of the YBa2Cu3O7-x superconductor.

Following the discovery of type-II high-temperature superconductors in 1986 (refs 1, 2), work has proceeded to develop these materials for power applications. One of the problems, however, has been that magnetic flux is not completely expelled, but rather is contained within magnetic fluxons, whose motion prevents larger supercurrents. It is known that the critical current of these materials can be enhanced by incorporating a high density of extended defects to act as pinning centres for the fluxons. YBa2Cu3O7 (YBCO or 123) is the most promising material for such applications at higher temperatures (liquid nitrogen). Pinning is optimized when the size of the defects approaches the superconducting coherence length ( approximately 2-4 nm for YBCO at temperatures < or =77 K) and when the areal number density of defects is of the order of (H/2) x 10(11) cm(-2), where H is the applied magnetic field in tesla. Such a high density has been difficult to achieve by material-processing methods that maintain a nanosize defect, except through irradiation. Here we report a method for achieving a dispersion of approximately 8-nm-sized nanoparticles in YBCO with a high number density, which increases the critical current (at 77 K) by a factor of two to three for high magnetic fields.

Repair of oesophageal atresia by consultants and supervised trainees results in similar outcomes.

INTRODUCTION: Consultants and trainees require exposure to complex cases for maintaining and gaining operative experience. Oesophageal atresia (OA) repair is a neonatal surgical procedure with indicative numbers for completion of training. A conflict of interest may exist between adequate training, maintaining consultant experience and achieving good outcomes. We aimed to review outcomes of procedures performed primarily by trainees and those performed by consultants. METHODS: We carried out a retrospective case note review of all consecutive infants who underwent surgical repair of OA with distal tracheooesophageal fistula (TOF) between January 1994 and December 2014 at our institution. Only cases that underwent primary oesophageal anastomosis were included. Surgical outcomes were compared between cases that had a trainee and those that had a consultant listed as the primary operator. RESULTS: One hundred and twenty-two cases were included. A total of 52 procedures were performed by trainees, and 68 by consultants. Two cases were undeterminable and excluded. Infant demographics, clinical characteristics and duration of follow-up were similar between groups. All infants survived to discharge. Procedures performed by trainees and those performed by consultants as primary operators had a similar incidence of postoperative pneumothorax (trainees 4, consultants 3; p=0.46), anastomotic leak (trainees 5, consultants 3; p=0.29) and recurrent TOF (trainees 0, consultants 2; p=0.5). Overall 52% of cases had an anastomotic dilatation during follow-up, with no difference between the trainee and consultant groups (50% vs 53%; p=0.85). CONCLUSIONS: Surgical outcomes for repair of OA/TOF are not adversely affected by trainee operating. Trainees with appropriate skills should perform supervised OA/TOF repair. These data are important for understanding the interrelationship between provision of training and surgical outcomes.

Gravitropism in plant stems may require ethylene.

Two inhibitors of ethylene synthesis in plants (cobaltous ion and aminoethoxyvinylglycine) and two inhibitors of ethylene action (silver ion and carbon dioxide) significantly delay the gravitropic response (upward bending) of mature dicot stems laid on their sides. This evidence suggests that ethylene may be required in the gravitropic response of shoots.

The giles county, virginia, seismic zone.

A well-defined seismic zone recently detected in Virginia has an orientation that is not related to the surrounding geologic structures. The orientation of the zone appears to be related to features below the Appalachian overthrust belt. A damaging earthquake that is important in evaluating seismic hazard in the southeastern United States may have occurred in the zone in 1897.

A seismotectonic model for the 300-kilometer-long eastern tennessee seismic zone.

Ten years of monitoring microearthquakes with a regional seismic network has revealed the presence of a well-defined, linear zone of seismic activity in eastern Tennessee. This zone produced the second highest release of seismic strain energy in the United States east of the Rocky Mountains during the last decade, when normalized by crustal area. The data indicate that seismicity produced by regional, intraplate stresses is now concentrating near the boundary between relatively strong and weak basement crustal blocks.

Susceptibility of selected freshwater fish species to a UK Lactococcus garvieae isolate.

Gram-positive cocci recovered from diseased rainbow trout from a farm in England were characterized by different methods, including pulsed field gel electrophoresis, as virulent Lactococcus garvieae serogroup 2 (pulsotype A1). Groups of rainbow trout were kept at a range of temperatures and injected intraperitoneally (i.p.) with one of the UK isolates, L. garvieae 00021. The 18 degrees C and 16 degrees C groups showed 67% and 28% mortality, respectively, by day 27 post-injection. Fish kept at 14 degrees C or lower were less susceptible (< or =3% mortality). Raising the temperature of all groups to 18 degrees C at day 27 post-injection did not result in recurrence of the disease, even though viable bacteria were recovered from all groups 42 days later. Grayling were highly susceptible, with 65% mortalities when challenged with 200 colony forming unit fish(-1) by i.p. injection and 37% mortalities when exposed to effluent water from tanks containing affected rainbow trout. Other fish species tested, Atlantic salmon, brown trout and seven cyprinid species, were less susceptible. Viable L. garvieae was isolated from the internal organs of all species tested at the end of the trials, suggesting that they may pose a threat as possible carriers to susceptible farmed and wild fish.

Effects of Various Commercially Available Enrichment Options on Handling and Chronic Stress Markers in Female ICR Mice.

Although social housing of mice generally is preferred, mice must be individually housed in some situations. In these cases, enhanced attention to environmental enrichment is encouraged, but few studies assess the wellbeing of mice provided various enrichments. In this study, we used female ICR mice to evaluate enrichment strategies that encouraged natural behaviors including foraging, exercise, sheltering, and socialization. After 3 mo of exposure to the assigned enrichment strategy, wellbeing was assessed by evaluating behavioral and physiologic differences between groups. The results suggested that the use of red-tinted igloos may decrease markers of mouse wellbeing. However, none of the selected strategies yielded measures of wellbeing indicating improvement as compared to individually housed mice with no enrichment (negative control). Furthermore, measures were not significantly different between paired mice and individually housed mice with no enrichment.

A strategic approach for investigating light recipes for 'Outredgeous' red romaine lettuce using white and monochromatic LEDs.

To optimize crop production/quality in space, we studied various "light recipes" that could be used in the Advanced Plant Habitat currently aboard the International Space Station (ISS). Lettuce (Lactuca sativa cv. 'Outredgeous') plants were grown for 28 days under seven treatments of white (W) LEDs (control), red (635 nm) and blue (460 nm) (RB) LEDs, W + blue (B) LEDs, W + green (520 nm) (G) LEDs, W + red (R) LEDs, W + far red (745 nm) (FR) LEDs, and RGB + FR LEDs with ratios similar to natural sunlight. Total PAR was maintained near 180 µmol m-2 s-1 with an 18 h photoperiod. Lettuce grown under RGB + FR produced the greatest leaf expansion and overall shoot biomass, while leaves from WB and RB showed the highest levels of pigmentation, secondary metabolites, and elemental nutrients. All other supplemental treatments had varying impacts on morphology that were dependent on crop age. The WG treatment increased fresh mass early in the cycle, while WR increased biomass later in the cycle. The plants grown under WFR exhibited elongation of petioles, lower nutrient content, and similar shoot biomass to the W control. The findings suggest that supplementing a broad spectrum, white light background with discrete wavelengths can be used to manipulate total yield, morphology, and levels of phytonutrients in lettuce at various times during the crop cycle.

Effect of acute hypoxia on vascular responsiveness in man. I. Responsiveness to lower body negative pressure and ice on the forehead. II. Responses to norepinephrine and angiotensin. 3. Effect of hypoxia and hypocapnia.

An effect of hypoxemia on vascular responsiveness and blood pressure regulation has not been demonstrated in man. The response of forearm resistance vessels to several vasoconstrictor stimuli was compared during normoxia and acute hypoxia. Forearm vasoconstrictor responses to lower body negative pressure and to the application of ice to the forehead, which are neurogenic stimuli, were decreased during acute hypoxia. Lower body negative pressure caused a decrease in mean arterial pressure during hypoxia, but not during normoxia. Because norepinephrine is the neurotransmitter released during reflex vasoconstriction, we considered the possibility that decreased responsiveness to norepinephrine might be one mechanism for diminished responses to lower body negative pressure and ice on the forehead during hypoxia. Hypoxia decreased the response of forearm resistance vessels to infusions of norepinephrine and angiotensin into the brachial artery. In addition, the effectiveness of intravenous infusions of norepinephrine in elevating mean arterial pressure was decreased during hypoxia. Since exposure to acute hypoxia stimulates hyperventilation and hypocapnia, experiments were done to determine the contribution of hypocapnia during hypoxia to the decreased vasoconstriction. The results indicate that hypocapnia may diminish the vascular response to some stimuli, but the reduction in oxygen appears to be the primary mechanism for decreased vasoconstrictor responses during acute hypoxia.

Effects of adrenergic stimulation on ventilation in man.

The mechanism by which catecholamines affect ventilation in man is not known. Ventilatory responses to catecholamines were observed in normal subjects before and after adrenergic receptor blockade. Intravenous infusions of norepinephrine and isoproterenol caused significant increases in minute volume and decreases in end-tidal P(Co2) which were blocked by the administration of propranolol, a beta adrenergic receptor blocker. The hyperventilatory response to hypoxia was not altered by propranolol. Intravenous infusion of phenylephrine caused a small but significant decrease in minute volume which was antagonized by phentolamine, an alpha adrenergic receptor blocker. Angiotensin, a nonadrenergic pressor agent, also decreased minute volume significantly.100% oxygen was administered to suppress arterial chemoreceptors. Increases in minute volume and decreases in arterial P(Co2) in response to norepinephrine and isoproterenol were blocked by breathing 100% oxygen. The decrease in minute volume during phenylephrine was not altered by 100% oxygen. THE RESULTS INDICATE THAT: (a) beta adrenergic receptors mediate the hyperventilatory response to norepinephrine and isoproterenol but not to hypoxia. (b) the pressor agents phenylephrine and angiotensin decrease ventilation, and (c) suppression of chemoreceptors blocks the ventilatory response to norepinephrine and isoproterenol but not to phenylephrine. Implications concerning the interaction of adrenergic receptors and chemoreceptors with respect to the hyperventilatory response to catecholamines are discussed.