A Case of Hyperkalemia Versus Pseudohyperkalemia in Chronic Lymphocytic Leukemia

Introduction: Both hyperkalemia and pseudohyperkalemia occur in the emergency department. True hyperkalemia necessitates emergent treatment while pseudohyperkalemia requires recognition to prevent inappropriate treatment. It is imperative that the emergency physician (EP) have an understanding of the causes and clinical presentations of both phenomena.Case Report: We present a case of an 88-year-old male with chronic lymphocytic leukemia (CLL) and suspected blast crisis who was found to have elevated serum potassium levels without other manifestations of hyperkalemia and eventually was determined to have pseudohyperkalemia due to white cell fragility.Discussion: Differentiation of hyperkalemia and pseudohyperkalemia is a critical skill for the EP. We discuss multiple causes of hyperkalemia and pseudohyperkalemia in an effort to broaden the knowledge base.Conclusion: We present a case of CLL as an unusual cause of pseudohyperkalemia and review common causes of pseudohyperkalemia

The COBE DIRBE Point Source Catalog

We present the COBE DIRBE Point Source Catalog, an all-sky catalog containing infrared photometry in 10 bands from 1.25 microns to 240 microns for 11,788 of the brightest near and mid-infrared point sources in the sky. Since DIRBE had excellent temporal coverage (100 - 1900 independent measurements per object during the 10 month cryogenic mission), the Catalog also contains information about variability at each wavelength, including amplitudes of variation observed during the mission. Since the DIRBE spatial resolution is relatively poor (0.7 degrees), we have carefully investigated the question of confusion, and have flagged sources with infrared-bright companions within the DIRBE beam. In addition, we filtered the DIRBE light curves for data points affected by companions outside of the main DIRBE beam but within the `sky' portion of the scan. At high Galactic latitudes (|b| > 5 degrees), the Catalog contains essentially all of the unconfused sources with flux densities greater than 90, 60, 60, 50, 90, and 165 Jy at 1.25, 2.2, 3.5, 4.9, 12, and 25 microns, respectively, corresponding to magnitude limits of approximately 3.1, 2.6, 1.7, 1.3, -1.3, and -3.5. At longer wavelengths and in the Galactic Plane, the completeness is less certain because of the large DIRBE beam and possible contributions from extended emission. The Catalog also contains the names of the sources in other catalogs, their spectral types, variability types, and whether or not the sources are known OH/IR stars. We discuss a few remarkable objects in the Catalog. [abridged]Comment: Accepted for publication in the Astrophysical Journal Supplement. The full tables are available at http://www.etsu.edu/physics/bsmith/dirbe

Evaluation of a workplace suicide prevention program in the Australian manufacturing industry : protocol for a cluster-randomised trial of MATES in manufacturing

Males are at higher risk of death by suicide than females in Australia, and among men, blue-collar males are at higher risk compared to other working males. In response, MATES in Construction developed a workplace suicide prevention program for the construction sector in 2007 that has been widely implemented in Australia. In the current project, this program is being adapted and trialled in the manufacturing sector. The common aims of MATES programs are to improve suicide prevention literacy, help-seeking intentions, and helping behaviours. The program will be evaluated using a cluster randomised-controlled trial design with waitlist controls across up to 12 manufacturing worksites in Australia. We hypothesise that after 8 months of the MATES in Manufacturing program, there will be significantly greater improvements in help-seeking intentions (primary outcome) compared to waitlist controls. The project is led by Deakin University in collaboration with the University of Melbourne, and in partnership with MATES in Construction and a joint labour-management Steering Group. Trial registration: The trial was registered retrospectively with the Australian New Zealand Clinical Trials Registry on 25 January 2022 (ACTRN12622000122752)

Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial

BACKGROUND: Natural amylin is a pancreatic hormone that induces satiety. Cagrilintide is a long-acting amylin analogue under investigation for weight management. We assessed the dose–response relationship of cagrilintide regarding the effects on bodyweight, safety, and tolerability. METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial at 57 sites including hospitals, specialist clinics, and primary care centres in ten countries (Canada, Denmark, Finland, Ireland, Japan, Poland, Serbia, South Africa, the UK, and the USA). Eligible participants were adults aged at least 18 years without diabetes, with a body-mass index of at least 30 kg/m^{2} or at least 27 kg/m^{2} with hypertension or dyslipidaemia. Participants were randomly assigned (6:1) to subcutaneous self-injections of once-weekly cagrilintide (0·3, 0·6, 1·2, 2·4, or 4·5 mg), once-daily liraglutide 3·0 mg, or volume-matched placebo (for six placebo groups). The trial had a 26-week treatment period, including a dose-escalation period of up to 6 weeks, and a 6-week follow-up period without treatment. Participants and investigators were masked to the assigned study treatment with respect to active versus pooled placebo treatment, but not to different active treatments. The primary endpoint was the percentage change in bodyweight from baseline to week 26, assessed in all randomly assigned participants according to the trial product estimand (assuming all participants were adherent to treatment) and to the treatment policy estimand (regardless of adherence to treatment). Safety was assessed in all participants who received at least one dose of randomised treatment. This trial is registered with ClinicalTrials.gov, NCT03856047, and is closed to new participants. FINDINGS: Between March 1 and Aug 19, 2019, we randomly assigned 706 participants to cagrilintide 0·3–4·5 mg (100–102 per dose group), 99 to liraglutide 3·0 mg, and 101 to placebo. Permanent treatment discontinuation (n=73 [10%]) occurred similarly across treatment groups, mostly due to adverse events (n=30 [4%]). In total, 29 participants (4%) withdrew from the trial. According to the trial product estimand, mean percentage weight reductions from baseline were greater with all doses of cagrilintide (0·3–4·5 mg, 6·0%–10·8% [6·4–11·5 kg]) versus placebo (3·0% [3·3 kg]; estimated treatment difference range 3·0%–7·8%; p<0·001). Weight reductions were also greater with cagrilintide 4·5 mg versus liraglutide 3·0 mg (10·8% [11·5 kg] vs 9·0% [9·6 kg]; estimated treatment difference 1·8%, p=0·03). Similar weight loss reductions were observed with the treatment policy estimand. The most frequent adverse events were gastrointestinal disorders (eg, nausea, constipation, and diarrhoea) and administration-site reactions. More participants receiving cagrilintide 0·3–4·5 mg had gastrointestinal adverse events compared with placebo (41%–63% vs 32%), primarily nausea (20%–47% vs 18%). INTERPRETATION: Treatment with cagrilintide in people with overweight and obesity led to significant reductions in bodyweight and was well tolerated. The findings support the development of molecules with novel mechanisms of action for weight management. FUNDING: Novo Nordisk A/S

Cross-species efficacy of enzyme replacement therapy for CLN1 disease in mice and sheep

CLN1 disease, also called infantile neuronal ceroid lipofuscinosis (NCL) or infantile Batten disease, is a fatal neurodegenerative lysosomal storage disorder resulting from mutations in the CLN1 gene encoding the soluble lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1). Therapies for CLN1 disease have proven challenging because of the aggressive disease course and the need to treat widespread areas of the brain and spinal cord. Indeed, gene therapy has proven less effective for CLN1 disease than for other similar lysosomal enzyme deficiencies. We therefore tested the efficacy of enzyme replacement therapy (ERT) by administering monthly infusions of recombinant human PPT1 (rhPPT1) to PPT1-deficient mice (Cln1-/-) and CLN1R151X sheep to assess how to potentially scale up for translation. In Cln1-/- mice, intracerebrovascular (i.c.v.) rhPPT1 delivery was the most effective route of administration, resulting in therapeutically relevant CNS levels of PPT1 activity. rhPPT1-treated mice had improved motor function, reduced disease-associated pathology, and diminished neuronal loss. In CLN1R151X sheep, i.c.v. infusions resulted in widespread rhPPT1 distribution and positive treatment effects measured by quantitative structural MRI and neuropathology. This study demonstrates the feasibility and therapeutic efficacy of i.c.v. rhPPT1 ERT. These findings represent a key step toward clinical testing of ERT in children with CLN1 disease and highlight the importance of a cross-species approach to developing a successful treatment strategy

Predicting total, abdominal, visceral and hepatic adiposity with circulating biomarkers in Caucasian and Japanese American women.

Characterization of abdominal and intra-abdominal fat requires imaging, and thus is not feasible in large epidemiologic studies.We investigated whether biomarkers may complement anthropometry (body mass index [BMI], waist circumference [WC], and waist-hip ratio [WHR]) in predicting the size of the body fat compartments by analyzing blood biomarkers, including adipocytokines, insulin resistance markers, sex steroid hormones, lipids, liver enzymes and gastro-neuropeptides.Fasting levels of 58 blood markers were analyzed in 60 healthy, Caucasian or Japanese American postmenopausal women who underwent anthropometric measurements, dual energy X-ray absorptiometry (DXA), and abdominal magnetic resonance imaging. Total, abdominal, visceral and hepatic adiposity were predicted based on anthropometry and the biomarkers using Random Forest models.Total body fat was well predicted by anthropometry alone (R(2) = 0.85), by the 5 best predictors from the biomarker model alone (leptin, leptin-adiponectin ratio [LAR], free estradiol, plasminogen activator inhibitor-1 [PAI1], alanine transaminase [ALT]; R(2) = 0.69), or by combining these 5 biomarkers with anthropometry (R(2) = 0.91). Abdominal adiposity (DXA trunk-to-periphery fat ratio) was better predicted by combining the two types of predictors (R(2) = 0.58) than by anthropometry alone (R(2) = 0.53) or the 5 best biomarkers alone (25(OH)-vitamin D(3), insulin-like growth factor binding protein-1 [IGFBP1], uric acid, soluble leptin receptor [sLEPR], Coenzyme Q10; R(2) = 0.35). Similarly, visceral fat was slightly better predicted by combining the predictors (R(2) = 0.68) than by anthropometry alone (R(2) = 0.65) or the 5 best biomarker predictors alone (leptin, C-reactive protein [CRP], LAR, lycopene, vitamin D(3); R(2) = 0.58). Percent liver fat was predicted better by the 5 best biomarker predictors (insulin, sex hormone binding globulin [SHBG], LAR, alpha-tocopherol, PAI1; R(2) = 0.42) or by combining the predictors (R(2) = 0.44) than by anthropometry alone (R(2) = 0.29).The predictive ability of anthropometry for body fat distribution may be enhanced by measuring a small number of biomarkers. Studies to replicate these data in men and other ethnic groups are warranted

Role of Human Polyomaviruses in Respiratory Tract Disease in Young Children

KI virus was detected in respiratory secretions of 8/367 (2.2%) symptomatic and 0/96 asymptomatic children (p = 0.215). WU virus was detected in 26/367 (7.1%) symptomatic and 6/96 (6.3%) asymptomatic children (p = 1.00). These human polyomaviruses may not independently cause respiratory tract disease in young children

Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

\u3cem\u3eStreptococcus agalactiae \u3c/em\u3eStrains with Chromosomal Deletions Evade Detection with Molecular Methods

Surveillance of circulating microbial populations is critical for monitoring the performance of a molecular diagnostic test. In this study, we characterized 31 isolates of Streptococcus agalactiae (group B Streptococcus [GBS]) from several geographic locations in the United States and Ireland that contain deletions in or adjacent to the region of the chromosome that encodes the hemolysin gene cfb, the region targeted by the Xpert GBS and GBS LB assays. PCR-negative, culture-positive isolates were recognized during verification studies of the Xpert GBS assay in 12 laboratories between 2012 and 2018. Whole-genome sequencing of 15 GBS isolates from 11 laboratories revealed four unique deletions of chromosomal DNA ranging from 181 bp to 49 kb. Prospective surveillance studies demonstrated that the prevalence of GBS isolates containing deletions in the convenience sample wa

STAGES: the Space Telescope A901/2 Galaxy Evolution Survey

We present an overview of the Space Telescope A901/2 Galaxy Evolution Survey (STAGES). STAGES is a multiwavelength project designed to probe physical drivers of galaxy evolution across a wide range of environments and luminosity. A complex multi-cluster system at z~0.165 has been the subject of an 80-orbit F606W HST/ACS mosaic covering the full 0.5x0.5 (~5x5 Mpc^2) span of the supercluster. Extensive multiwavelength observations with XMM-Newton, GALEX, Spitzer, 2dF, GMRT, and the 17-band COMBO-17 photometric redshift survey complement the HST imaging. Our survey goals include simultaneously linking galaxy morphology with other observables such as age, star-formation rate, nuclear activity, and stellar mass. In addition, with the multiwavelength dataset and new high resolution mass maps from gravitational lensing, we are able to disentangle the large-scale structure of the system. By examining all aspects of environment we will be able to evaluate the relative importance of the dark matter halos, the local galaxy density, and the hot X-ray gas in driving galaxy transformation. This paper describes the HST imaging, data reduction, and creation of a master catalogue. We perform Sersic fitting on the HST images and conduct associated simulations to quantify completeness. In addition, we present the COMBO-17 photometric redshift catalogue and estimates of stellar masses and star-formation rates for this field. We define galaxy and cluster sample selection criteria which will be the basis for forthcoming science analyses, and present a compilation of notable objects in the field. Finally, we describe the further multiwavelength observations and announce public access to the data and catalogues.Comment: 29 pages, 22 figures; accepted to MNRAS. Full data release available at http://www.nottingham.ac.uk/astronomy/stage