Milk osteopontin retains integrin-binding activity after in vitro gastrointestinal transit.

Osteopontin (OPN) is a multifunctional protein highly expressed in milk, where it is hypothesized to be involved in immunological signaling via the conserved Arg-Gly-Asp (RGD) integrin-binding sequence. Intervention studies have indicated beneficial effects of orally administered OPN in animal and human infants, but the mechanisms underlying these effects are not well described. To induce physiological effects, OPN must resist gastrointestinal transit in a bioactive form. In this study, we subjected bovine milk OPN to in vitro gastrointestinal transit, and characterized the generated fragments using monoclonal antibody and mass spectrometric analyses. We found that the fragment Trp27-Phe151 containing the integrin-binding RGD sequence resisted in vitro gastric digestion. This resistance was dependent on glycosylation of threonine residues near the integrin-binding sequence in both human and bovine milk OPN. Furthermore, the fragment Trp27-Phe151 retained the ability to interact with integrins in an RGD-dependent process. These results suggest a mechanism for how ingested milk OPN can induce physiological effects via integrin signaling in the intestine.

Multicenter Study of the Real-World Use of Ceftaroline versus Vancomycin for Acute Bacterial Skin and Skin Structure Infections.

The objective of this study was to determine if real-world ceftaroline treatment in adults hospitalized for acute bacterial skin and skin structure infections (ABSSSI) is associated with decreased infection-related length of stay (LOSinf) compared to that with vancomycin. This was a retrospective, multicenter, cohort study from 2012 to 2017. Cox proportional hazard regression, propensity score matching, and inverse probability of treatment weighting (IPTW) were used to determine the independent effect of treatment group on LOSinf The patients were adults hospitalized with ABSSSI and treated with ceftaroline or vancomycin for ≥72 h within 120 h of diagnosis at four academic medical centers and two community hospitals in Arizona, Florida, Michigan, and West Virginia. A total of 724 patients were included (325 ceftaroline treated and 399 vancomycin treated). In general, ceftaroline-treated patients had characteristics consistent with a higher risk of poor outcomes. The unadjusted median LOSinf values were 5 (interquartile range [IQR], 3 to 7) days and 6 (IQR, 4 to 8) days in the vancomycin and ceftaroline groups, respectively (hazard ratio [HR], 0.866; 95% confidence interval [CI], 0.747 to 1.002). The Cox proportional hazard model (adjusted HR [aHR], 0.891; 95% CI, 0.748 to 1.060), propensity score-matched (aHR, 0.955; 95% CI, 0.786 to 1.159), and IPTW (aHR, 0.918; 95% CI, 0.793 to 1.063) analyses demonstrated no significant difference in LOSinf between groups. Patients treated with ceftaroline were significantly more likely to meet criteria for discharge readiness at day 3 in unadjusted and adjusted analyses. Although discharge readiness at day 3 was higher in ceftaroline-treated patients, LOSinf values were similar between treatment groups. Clinical and nonclinical factors were associated with LOSinf.

New insights into early recovery after robotic surgery for endometrial cancer.

OBJECTIVE: To assess early recovery of physical health after robotic minimally invasive surgery (RMIS) for early-stage endometrial cancer using the European Organisation of Research and Treatment of Cancer Computer Adaptive Test Core questionnaire (EORTC CAT Core). The EORTC CAT Core provides individualised measurements while maintaining comparability. A hypothesis of individual complete recovery to baseline within three post-surgical weeks was evaluated. METHODS: Ninety-four women who underwent RMIS for early-stage endometrial cancer were included consecutively. The EORTC CAT Core was distributed before surgery and prospectively every week during the first post-operative month. Repeated measures models were fitted for each of the four domains (physical functioning, role function, fatigue, and pain) and tested for impact of age, ASA score, minor/major surgery, and the individual baseline scores (poorest, intermediate, best). RESULTS: Women with the lowest physical functioning, lowest role function, highest fatigue level, and highest pain level at baseline all recovered within three weeks. Women with the highest physical functioning, highest role function, lowest level of fatigue, and lowest level of pain at baseline did not reach their individual baselines within the first post-operative month but had the most favourable domain-scores three weeks post-operatively. CONCLUSION: The individual woman's physical health baseline score is predictive for her postoperative recovery following RMIS for early-stage endometrial cancer. Women with the best physical health had the best postoperative functions and lowest level of symptoms; however their recovery to baseline was prolonged. Computer adaptive testing may be a valuable tool for individualised pre-operative information and supportive care during surveillance.

Defective RNA sensing by RIG-I in severe influenza virus infection.

Influenza virus infection causes worldwide seasonal epidemics. Although influenza is usually a mild disease, a minority of patients experience very severe fulminating disease courses. Previous studies have demonstrated a role for type I interferon (IFN) in anti-viral responses during influenza. So far, however, IFN regulatory factor (IRF)7 deficiency is the only genetic cause of severe influenza described in humans. In this study we present a patient with severe influenza A virus (IAV) H1N1 infection during the 2009 swine flu pandemic. By whole exome sequencing we identified two variants, p.R71H and p.P885S, located in the caspase activation and recruitment domain (CARD) and RNA binding domains, respectively, of DExD/H-box helicase 58 (DDX58) encoding the RNA sensor retinoic acid inducible gene 1 (RIG-I). These variants significantly impair the signalling activity of RIG-I. Similarly, patient cells demonstrate decreased antiviral responses to RIG-I ligands as well as increased proinflammatory responses to IAV, suggesting dysregulation of the innate immune response with increased immunopathology. We suggest that these RIG-I variants may have contributed to severe influenza in this patient and advocate that RIG-I variants should be sought in future studies of genetic factors influencing single-stranded RNA virus infections.

Pregnancy outcome in four women with inflammatory bowel disease treated with budesonide MMX.

BACKGROUND: Maintaining disease remission throughout pregnancy in women with inflammatory bowel disease is of the utmost importance to decrease the risk of adverse outcome. In general, corticosteroids are safe to use during pregnancy, but no data exist in the specific use of budesonide MMX. We report four cases of budesonide MMX in pregnancy and pregnancy outcome. METHODS: Four women with inflammatory bowel disease experienced disease activity during pregnancy. They were treated with budesonide MMX in an attempt to obtain clinical remission. Disease activity was assessed through physician's global assessment as well as lower endoscopy. RESULTS: Budesonide MMX proved effective in achieving remission in three out of four women. One woman had an uncomplicated colectomy in the second trimester. All children were born normal for gestational age, with no congenital abnormalities and have reached all their developmental milestones. The four children have received vaccines according to the national immunization program without complications. CONCLUSION: No adverse pregnancy outcomes were reported after the use of budesonide MMX. To our knowledge, this is the first report on the safety of budesonide MMX treatment in pregnant women with inflammatory bowel disease.

A three-phase excess post-exercise oxygen consumption in Atlantic salmon Salmo salar and its response to exercise training.

The recovery of oxygen uptake to the standard metabolic rate (SMR) following exhaustive chasing exercise in Atlantic salmon Salmo salar parr occurred in three phases (rapid, plateau and slow). The initial recovery phase lasted 0·7 h and contributed 16% to the total excess post-exercise oxygen consumption (EPOC). It was followed by a longer plateau phase that contributed 53% to the total EPOC. The slow recovery phase that completed recovery of SMR, which has not been reported previously, made a 31% contribution to the total EPOC. The plasticity of EPOC was demonstrated in exercise-trained fish. Exercise training increased EPOC by 39% when compared with control fish (mean ± S.E., 877·7 ± 73·1 v. 629·2 ± 53·4 mg O2 kg-1 , d.f. = 9, P < 0·05), with the duration of the plateau phase increasing by 38% (4·7 ± 0·58 v. 3·4 ± 0·16 h, d.f. = 9, P < 0·05) and the contribution of the slow phase to the total EPOC increasing by 80% (173·9 ± 23·9 v. 312·5 ± 50·4 mg O2 kg-1 , d.f. = 9, P < 0·05). As a result, the combination of the plateau and slow phases of exercise-trained fish increased by 47% compared with control fish (756·6 ± 71·4 v. 513·6 ± 43·1 mg O2 kg-1 ; d.f. = 9, P = 0·01). To substantiate the hypothesis that the plateau and slow recovery phase of EPOC was related to general metabolic recovery following exhaustive exercise, the time-course for recovery of SMR was compared with previously published metabolite recovery profiles. The final phase of metabolic recovery was temporally associated with the final phases of gluconeogenesis, lactate oxidation and muscle intracellular pH regulation. Therefore, the plasticity of the latter phase of EPOC agreed with the known effects of exercise training in fishes.

Emergency Department Urinary Antibiograms Differ by Specific Patient Group.

Patients presenting to the emergency department (ED) represent a heterogeneous population comprised of all ages, various backgrounds, such as from the community and skilled-nursing facilities (SNFs), and at various risks for resistant pathogens. The aim of this study was to compare patient group-specific urinary antibiograms in the ED. Adults presented to the ED with an ICD 9/10 code urinary tract infection (UTI) diagnosis during July 2015 to June 2016 were randomly selected (n = 500) to extract relevant demographic, laboratory, and clinical data from the medical record. Urinary Escherichia coli antibiograms were compared between institutional versus ED and among ED patients (male versus female; age of 18 to 64 years versus ≥65 years; female aged 18 to 50 years versus >50 years; home versus SNF; and admitted versus discharged). E. coli grew from 56% (145/259) of the positive urine cultures. Overall ciprofloxacin (CIP), trimethoprim-sulfamethoxazole (SXT), and cefazolin (CFZ) susceptibilities were <71%. Differences in antibiograms were the following: lower CFZ and SXT susceptibilities in ED versus institutional (CFZ, 67% versus 86% [P = 0.001]; SXT, 66% versus 74% [P = 0.02]), lower ampicillin and gentamicin susceptibilities in females aged 18 to 50 years versus >50 years (32% versus 52% [P = 0.04]; 78% versus 93% [P = 0.02]), lower CIP susceptibilities in the elderly (64% versus 81%; P = 0.03), SNF versus home (35% versus 77%; P < 0.001), admitted versus discharged (63% versus 78%; P = 0.04), and lower SXT susceptibilities in patients aged <65 years versus the elderly (58% versus 71%; P = 0.01). Nitrofurantoin showed >80% susceptibility in all groups. Patient group-specific urinary antibiograms revealed distinct differences in E. coli susceptibility and should be developed to better inform empirical UTI therapy selection in the ED.

Emerging multidrug-resistant Bengal Bay clone ST772-MRSA-V in Norway: molecular epidemiology 2004-2014.

A multidrug-resistant, methicillin-resistant Staphylococcus aureus (MRSA) clone, PVL-positive ST772-MRSA-V, named the Bengal Bay clone, is emerging worldwide. In Norway, where MRSA prevalence is low, a sudden increase in ST772-MRSA-V initiated a nationwide molecular epidemiological study. Clinical data were obtained from the Norwegian Surveillance System for Communicable Diseases (MSIS). S. aureus isolates were characterised by antibiotic susceptibility profiles and comprehensive genotyping (spa typing, MLVA, DNA microarray). ST772-MRSA was detected in 145 individuals during 2004-2014, with 60% of cases occurring in 2013-2014. Median age was 31 years and male/female ratio 1.16. The majority had a family background from the Indian subcontinent (70%). MRSA acquisition was mainly reported as unknown (39%) or abroad (42%), the latter associated with a home-country visit (59%), tourism (16%), and immigration (13%). Clinical infection was present in 75%, predominantly by SSTI (83%), 18% were admitted to hospital and 42% were linked to small-scale outbreaks (n = 25). All isolates were multidrug-resistant. Most isolates were resistant to erythromycin, gentamicin and norfloxacin. Genotyping revealed a conserved clone predominated by spa type t657 (83%), MLVA-type 432 (67%) and the genes lukF/S, sea, sec/sel, egc, scn, cna, ccrAA/ccrC, agrII and cap5. A few untypical ccr gene combinations were detected. Bengal Bay isolates have likely been imported on several occasions and revision of infection control guidelines may prevent further spread.

Characterization of Enterococcus faecalis isolated from the cloaca of 'fancy breeds' and confined chickens.

AIMS: The aim was to investigate the intestinal community of Enterococcus faecalis from healthy confined non-industrialized chicken. METHODS AND RESULTS: A total of 206 E. faecalis isolates were collected from cloacal swabs. The prevalence of E. faecalis from two confined flocks was 83 and 96%, while only 44 and 13% in two fancy breeder flocks. A total of 204 isolates were characterized by pulsed-field-gel-electrophoresis (PFGE) where 40 strains were selected for multi-locus sequence typing (MLST). In all, 19 PFGE patterns and 14 STs were obtained. Four STs were identified in each of the two confined flocks, with one shared ST, while seven STs were identified in the two fancy breeder flocks. Only six of the identified STs had previously been registered in chicken. CONCLUSION: The majority of clonal lineages of E. faecalis associated with chicken reared in confinement and under backyard conditions were unrelated. SIGNIFICANCE AND IMPACT OF THE STUDY: This study has provided new information on opportunistic E. faecalis in confined non-industrial chicken. Knowledge of population diversity and prevalence compared to conventional production is important to accesses, if certain clonal lineages are more likely to be associated with other intestinal E. faecalis lineages in chicken, and it is an important tool for gaining control of clones involved in disease and antibiotic resistance.

Tracking apex marine predator movements in a dynamic ocean.

Pelagic marine predators face unprecedented challenges and uncertain futures. Overexploitation and climate variability impact the abundance and distribution of top predators in ocean ecosystems. Improved understanding of ecological patterns, evolutionary constraints and ecosystem function is critical for preventing extinctions, loss of biodiversity and disruption of ecosystem services. Recent advances in electronic tagging techniques have provided the capacity to observe the movements and long-distance migrations of animals in relation to ocean processes across a range of ecological scales. Tagging of Pacific Predators, a field programme of the Census of Marine Life, deployed 4,306 tags on 23 species in the North Pacific Ocean, resulting in a tracking data set of unprecedented scale and species diversity that covers 265,386 tracking days from 2000 to 2009. Here we report migration pathways, link ocean features to multispecies hotspots and illustrate niche partitioning within and among congener guilds. Our results indicate that the California Current large marine ecosystem and the North Pacific transition zone attract and retain a diverse assemblage of marine vertebrates. Within the California Current large marine ecosystem, several predator guilds seasonally undertake north-south migrations that may be driven by oceanic processes, species-specific thermal tolerances and shifts in prey distributions. We identify critical habitats across multinational boundaries and show that top predators exploit their environment in predictable ways, providing the foundation for spatial management of large marine ecosystems.

Leisure time physical activity among older adults with long-term spinal cord injury.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To describe participation in leisure time physical activity (LTPA) (amount, intensity and type) among older adults with long-term spinal cord injury (SCI), and to investigate the associations with sociodemographics, injury characteristics and secondary health conditions (SHCs). SETTING: Home settings in southern Sweden. METHODS: Data from the Swedish Aging with Spinal Cord Injury Study (SASCIS). The physical activity recall assessment for people with SCI was used to assess LTPA among 84 men and 35 women (mean age 63.5 years, mean time since injury 24 years, injury levels C1-L5, American Spinal Injury Association Impairment Scale A-D). Associations were analyzed statistically using hierarchical multivariable regression. RESULTS: Twenty-nine percent reported no LTPA, whereas 53% performed moderate-to-heavy intensity LTPA. The mean minutes per day of total LTPA was 34.7 (±41.5, median 15, range 0-171.7) and of moderate-to-heavy LTPA 22.5 (±35.1, median 5.0, range 0-140.0). The most frequently performed activities were walking and wheeling. Sociodemographics, injury characteristics and SHCs (bowel-related and bladder-related problems, spasticity and pain) explained 10.6% and 13.4%, respectively, of the variance in total and moderate-to-heavy LTPA. Age and wheelchair use were significantly, negatively associated with total LTPA. Women, wheelchair users and employed participants performed significantly less moderate-to-heavy LTPA than men, those using walking devices/no mobility device and unemployed participants. CONCLUSION: Many older adults with long-term SCI do not reach the amount or intensity of LTPA needed to achieve fitness benefits. Research is needed on how to increase LTPA and to identify modifiable factors that could enhance their participation.

Activating PI3Kδ mutations in a cohort of 669 patients with primary immunodeficiency.

The gene PIK3CD codes for the catalytic subunit of phosphoinositide 3-kinase δ (PI3Kδ), and is expressed solely in leucocytes. Activating mutations of PIK3CD have been described to cause an autosomal dominant immunodeficiency that shares clinical features with common variable immunodeficiency (CVID). We screened a cohort of 669 molecularly undefined primary immunodeficiency patients for five reported mutations (four gain-of-function mutations in PIK3CD and a loss of function mutation in PIK3R1) using pyrosequencing. PIK3CD mutations were identified in three siblings diagnosed with CVID and two sporadic cases with a combined immunodeficiency (CID). The PIK3R1 mutation was not identified in the cohort. Our patients with activated PI3Kδ syndrome (APDS) showed a range of clinical and immunological findings, even within a single family, but shared a reduction in naive T cells. PIK3CD gain of function mutations are more likely to occur in patients with defective B and T cell responses and should be screened for in CVID and CID, but are less likely in patients with a pure B cell/hypogammaglobulinaemia phenotype.

A novel application of multi-event modeling to estimate class segregation in a highly migratory oceanic vertebrate.

Spatial segregation of animals by class (i.e., maturity or sex) within a population due to differential rates of temporary emigration (TE) from study sites can be an important life history feature to consider in population assessment and management. However, such rates are poorly known; new quantitative approaches to address these knowledge gaps are needed. We present a novel application of multi-event models that takes advantage of two sources of detections to differentiate temporary emigration from apparent absence to quantify class segregation within a study population of double-marked (photo-identified and tagged with coded acoustic transmitters) white sharks (Carcharodon carcharias) in central California. We use this model to test if sex-specific patterns in TE result in disparate apparent capture probabilities (po ) between male and female white sharks, which can affect the observed sex ratio. The best-supported model showed a contrasting pattern of Pr(TE) from coastal aggregation sites between sexes (for males Pr[TE] = 0.015 [95% CI = 0.00, 0.31] and Pr[TE]= 0.57 [0.40, 0.72] for females), but not maturity classes. Additionally, by accounting for Pr(TE) and imperfect detection, we were able to estimate class-specific values of true capture probability (p* ) for tagged and untagged sharks. The best-supported model identified differences between maturity classes but no difference between sexes or tagging impacts (tagged mature sharks p*  = 0.55 (0.46-0.63) and sub-adult sharks p*  = 0.36 (0.25, 0.50); and untagged mature sharks p*  = 0.50 (0.39-0.61) and sub-adults p*  = 0.18 (0.10, 0.31). Estimated sex-based differences in po were linked to sex-specific differences in Pr(TE) but not in p* ; once the Pr(TE) is accounted for, the p* between sexes was not different. These results indicate that the observed sex ratio is not a consequence of unequal detectability and sex-specific values of Pr(TE) are important drivers of the observed male-dominated sex ratio. Our modeling approach reveals complex class-specific patterns in Pr(TE) and p* in a mark-recapture data set, and highlights challenges for the population modeling and conservation of white sharks in central California. The model we develop here can be used to estimate rates of temporary emigration and class segregation when two detection methods are used.

Prenatal exposure to systemic antibacterials and overweight and obesity in Danish schoolchildren: a prevalence study.

BACKGROUND/OBJECTIVE: Prenatal exposure to antibacterials may permanently dysregulate fetal metabolic patterns via epigenetic pathways or by altering maternal microbiota. We examined the association of prenatal exposure to systemic antibacterials with overweight and obesity in schoolchildren. SUBJECTS/METHODS: We conducted a prevalence study among Danish schoolchildren aged 7-16 years using data from routine school anthropometric evaluations conducted during 2002-2013. Prenatal exposure to antibacterials was ascertained by using maternal prescription dispensations and infection-related hospital admissions during pregnancy. We defined overweight and obesity among the children using standard age- and sex-specific cutoffs. We computed sex-specific adjusted prevalence ratios (aPRs) of overweight and obesity associated with exposure to prenatal antibacterials, adjusting for maternal age at delivery, marital status, smoking in pregnancy and multiple gestation; we also stratified the analyses by birth weight. RESULTS: Among 9886 schoolchildren, 3280 (33%) had prenatal exposure to antibacterials. aPRs associated with the exposure were 1.26 (95% confidence interval (CI): 1.10-1.45) for overweight and 1.29 (95% CI: 1.03-1.62) for obesity. Among girls, aPRs were 1.16 (95% CI: 0.95-1.42) for overweight and 1.27 (95% CI: 0.89 to 1.82) for obesity. Among boys, aPRs were 1.37 (95% CI: 1.13-1.66) for overweight and 1.29 (95% CI: 0.96-1.73) for obesity. The aPR for overweight was higher among schoolchildren with birth weight <3500 g (aPR: 1.30, 95% CI: 1.05-1.61) than in schoolchildren with birth weight ⩾3500 g (aPR: 1.18, 95% CI: 0.95-1.46). Inversely, the association for obesity was higher among schoolchildren with birth weight ⩾3500 g (aPR: 1.35, 95% CI: 1.00-1.81) than among those who were <3500 g at birth (aPR: 1.16, 95% CI: 0.82-1.65). CONCLUSIONS: Prenatal exposure to systemic antibacterials is associated with an increased risk of overweight and obesity at school age, and this association varies by birth weight.

Flow cytometry detection of vitamin D receptor changes during vitamin D treatment in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory disease associated with a dysregulated T cell response towards intestinal microflora. Vitamin D has immune modulatory effects on T cells through the nuclear vitamin D receptor (VDR) in vitro. It is unclear how oral vitamin D treatment affects VDR expression. The aim of this study was to establish a flow cytometry protocol, including nuclear and cytoplasmic VDR expression, and to investigate the effects of vitamin D treatment on T cell VDR expression in CD patients. The flow cytometry protocol for VDR staining was developed using the human acute monocytic leukaemia cell line (THP-1). The protocol was evaluated in anti-CD3/CD28-stimulated peripheral blood mononuclear cells (PBMCs) from vitamin D3- (n = 9) and placebo-treated (n = 9) CD patients. Anti-VDR-stained PBMCs were examined by flow cytometry, and their cytokine production was determined by cytokine bead array. VDR, CYP27B1 and RXRα mRNA expression levels in CD4(+) T cells were measured by quantitative reverse transcriptase polymerase chain reaction. The flow cytometry protocol enabled detection of cytoplasmic and nuclear VDR expression. The results were confirmed by confocal microscopy and supported by correlation with VDR mRNA expression. VDR expression in CD4(+) T cells increased following stimulation. This VDR up-regulation was inhibited with 30% by vitamin D treatment compared to placebo in CD patients (P = 0027). VDR expression was correlated with in-vitro interferon-γ production in stimulated PBMCs (P = 0.01). Flow cytometry is a useful method with which to measure intracellular VDR expression. Vitamin D treatment in CD patients reduces T cell receptor-mediated VDR up-regulation.

Epidural steroid injections in the management of cervical disc herniations with radiculopathy.

OBJECTIVES: To evaluate the efficacy and safety of cervical epidural steroid injection (CESI) in the management of cervical disc herniations with radiculopathy. METHOD: We conducted a prospective interventional study with a 1-year follow-up comprising 33 consecutive patients presenting symptoms of cervicobrachial pain; positive neurological signs; corresponding cervical disc herniation/protrusion as verified by magnetic resonance imaging (MRI); insufficient improvement on prior conservative therapy; and no claims for financial compensation. Symptoms and clinical findings were registered in validated questionnaires before the procedure. Blind midline interlaminar CESI at the level of disc herniation was administered utilizing the loss of resistance (LOR) technique. Outcome was assessed during the first 3 months by telephone interview or clinical examination and final outcome measures were obtained at 1 year using validated questionnaires. RESULTS: The study included 20 men (60%) and 13 women (40%); median age was 51 (range 30-63) years. Median duration of neck and arm pain was 72 (7-450) and 64 (5-443) days, respectively. On average, patients received 1.7 CESIs (range 1-3). Sixteen patients (49%) had only one injection. All 33 patients were potentially surgical candidates. Only two (6%) needed surgical intervention during follow-up. There was significant improvement in pain intensity and functional outcome. Intake of analgesics was significantly reduced. Eighty-two per cent would say 'yes' to receiving the same treatment again. No serious adverse events were observed. CONCLUSIONS: CESI appears to be a safe and efficient part of the treatment of patients with symptomatic cervical disc herniations and may be considered before patients are referred to surgery.

Mid-term follow-up of patients with permanent sequel due to spinal cord ischemia after advanced endovascular therapy for extensive aortic disease.

STUDY DESIGN: Observational study. OBJECTIVES: Thoraco-abdominal endovascular aortic aneurysm repair (TAEVAR) can be used to treat patients with extensive and complex aortic disease, however, at the risk of spinal cord ischemia (SCI). The aim of this follow-up study was to evaluate the life satisfaction in patients with SCI after TAEVAR. SETTING: Among 83 patients undergoing TAEVAR between 2009 and 2012 at the Vascular Centre, Malmö, Sweden, 29 developed SCI in-hospital and at follow-up (median 26 months), eight had died and three had no complaints. METHODS: Patients diagnosed with permanent (n=10) and transient (n=8) SCI were interviewed at home. The Life Satisfaction Questionnaire (LiSat-11) and the Satisfaction With Life Scale (SWLS) were compared with reference samples. RESULTS: Mid-term mortality in patients with permanent SCI (7/17) was higher than those with transient SCI (1/12) (P=0.035). Ten patients had permanent T1-S5 SCI, two were classified as ASIA Impairment Scale (AIS) A, one as AIS B and seven as AIS D at hospital discharge. Patients diagnosed with transient SCI had residual neurological deficits in the legs (n=8), urge incontinence (n=3) and fecal leakage (n=2) at follow-up. Patients with SCI had lower self-rated life satisfaction in terms of 'life as a whole', 'sexual life', 'somatic health' and 'psychological health' but better in the 'economy' domain. CONCLUSION: Assessment of life satisfaction at mid-term follow-up suggests that all patients with SCI in-hospital, whether permanent or transient, should have a multi-disciplinary follow-up regime. Most patients diagnosed with transient neurological deficits had an overlooked permanent, less severe, SCI.

Glucose metabolism is altered after loss of L cells and α-cells but not influenced by loss of K cells.

The enteroendocrine K and L cells are responsible for secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon like-peptide 1 (GLP-1), whereas pancreatic α-cells are responsible for secretion of glucagon. In rodents and humans, dysregulation of the secretion of GIP, GLP-1, and glucagon is associated with impaired regulation of metabolism. This study evaluates the consequences of acute removal of Gip- or Gcg-expressing cells on glucose metabolism. Generation of the two diphtheria toxin receptor cellular knockout mice, TgN(GIP.DTR) and TgN(GCG.DTR), allowed us to study effects of acute ablation of K and L cells and α-cells. Diphtheria toxin administration reduced the expression of Gip and content of GIP in the proximal jejunum in TgN(GIP.DTR) and expression of Gcg and content of proglucagon-derived peptides in both proximal jejunum and terminal ileum as well as content of glucagon in pancreas in TgN(GCG.DTR) compared with wild-type mice. GIP response to oral glucose was attenuated following K cell loss, but oral and intraperitoneal glucose tolerances were unaffected. Intraperitoneal glucose tolerance was impaired following combined L cell and α-cell loss and normal following α-cell loss. Oral glucose tolerance was improved following L cell and α-cell loss and supernormal following α-cell loss. We present two mouse models that allow studies of the effects of K cell or L cell and α-cell loss as well as isolated α-cell loss. Our findings show that intraperitoneal glucose tolerance is dependent on an intact L cell mass and underscore the diabetogenic effects of α-cell signaling. Furthermore, the results suggest that K cells are less involved in acute regulation of mouse glucose metabolism than L cells and α-cells.

Meeting the challenges of wound care in Danish home care.

OBJECTIVE: To evaluate a community-based educational intervention to improve wound-care practice, and thereby reduce the costs of care, in four communities in Denmark. METHOD: Annual wound care audits recorded patients' ages, the number and types of wounds being treated, wound duration (days unhealed), frequency of dressing changes and nurse time per dressing change. Data were available at year 1 and year 3 post-intervention. A statistical analysis was performed, testing for changes in a range of variables between these years. RESULTS: In the post-intervention period, significant reductions were found in the proportion of chronic wounds, the proportion of wounds requiring a daily dressing change, mean frequency of dressing change, mean nurse time spent in wound care per week, and the total cost of wound care per week. CONCLUSION: These results suggest that it is possible to improve wound-care practice and reduce the resource costs of wound care through a systematic programme of education and training, tailored to suit the needs of local communities.

Lessons learned: use of WGS in real-time investigation of suspected intrahospital SARS-CoV-2 outbreaks.

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been a continuing source of hospital-acquired infection and outbreaks. At Akershus University Hospital in Norway, traditional contact tracing has been combined with whole-genome sequencing (WGS) surveillance in real-time to investigate potential hospital outbreaks. AIM: To describe the advantages and challenges encountered when using WGS as a real-time tool in hospital outbreak investigation and surveillance during the SARS-CoV-2 pandemic. METHODS: Routine contact tracing in the hospital was performed for all healthcare workers (HCWs) who tested positive for SARS-CoV-2. Viral RNA from all positive patient and HCW samples was sequenced in real-time using nanopore sequencing and the ARTIC Network protocol. Suspected outbreaks involving five or more individuals with viral sequences were described. FINDINGS: Nine outbreaks were suspected based on contact tracing, and one outbreak was suspected based on WGS results. Five outbreaks were confirmed; of these, two outbreaks were supported but could not be confirmed by WGS with high confidence, one outbreak was found to consist of two different lineages, and two outbreaks were refuted. CONCLUSIONS: WGS is a valuable tool in hospital outbreak investigations when combined with traditional contact tracing. Inclusion of WGS data improved outbreak demarcation, identified unknown transmission chains, and highlighted weaknesses in existing infection control measures.