Outlier or handover: outcomes for General Medicine inpatients.

Objective Patients admitted from the emergency department may be co-located on the treating team's 'home ward'. If no bed is available, patients may be sent to another ward, where they may remain under the admitting team as an 'outlier'. Conversely, care may be handed over to the team on whose home ward they are located. We conducted a retrospective analysis to understand the impact of outlier status and handovers of care on outcomes for General Medicine inpatients. Methods General Medicine admissions at the Royal Adelaide Hospital between September 2020 and November 2021 were analysed. We examined the rate of hospital-acquired complications, inpatient mortality rate, mortality within 48 h of admission, Relative Stay Index, time of discharge from hospital and rate of adverse events within 28 days of discharge. Results A total of 3109 admissions were analysed. Handovers within 24 h of admission were associated with a longer length of stay. There was a trend towards higher rates of adverse events within 28 days of discharge with handovers of care. Outlier status did not affect any outcome measures. Conclusions Handovers within the first 24 h of admission are associated with longer than expected length of stay.

Higher procoagulatory potential but lower DIC score in COVID-19 ARDS patients compared to non-COVID-19 ARDS patients.

BACKGROUND: COVID-19 is a novel viral disease. Severe courses may present as ARDS. Several publications report a high incidence of coagulation abnormalities in these patients. We aimed to compare coagulation and inflammation parameters in patients with ARDS due to SARS-CoV-2 infection versus patients with ARDS due to other causes. METHODS: This retrospective study included intubated patients admitted with the diagnosis of ARDS to the ICU at Munich university hospital. 22 patients had confirmed SARS-CoV2-infection (COVID-19 group), 14 patients had bacterial or other viral pneumonia (control group). Demographic, clinical parameters and laboratory tests including coagulation parameters and thromboelastometry were analysed. RESULTS: No differences were found in gender ratios, BMI, Horovitz quotients and haemoglobin values. The median SOFA score, serum lactate levels, renal function parameters (creatinine, urea) and all inflammation markers (IL-6, PCT, CRP) were lower in the COVID-19 group (all: p < 0.05). INR (p < 0.001) and antithrombin (p < 0.001) were higher in COVID-19 patients. D-dimer levels (p = 0.004) and consecutively the DIC score (p = 0.003) were lower in this group. In ExTEM®, Time-to-Twenty (TT20) was shorter in the COVID-19 group (p = 0.047), these patients also had higher FibTEM® MCF (p = 0.005). Further, these patients presented with elevated antigen and activity levels of von-Willebrand-Factor (VWF). CONCLUSION: COVID-19 patients presented with higher coagulatory potential (shortened global clotting tests, increased viscoelastic and VWF parameters), while DIC scores were lower. An intensified anticoagulation regimen based on an individual risk assessment is advisable to avoid thromboembolic complications.

Non-financial conflicts of interest: contribution to a surgical dilemma by the European Reference Networks for Rare Diseases.

PURPOSE: Conflicts of interest can impede both research and medical treatment. The European Reference Networks require their members to deal with financial and non-financial conflicts according to an explicit protocol. In a literature review, we identified relevant interests in paediatric surgery, and drafted such a policy. METHODS: We conducted a Pubmed query and identified additional publications based on the content of the papers. RESULTS: 58 titles were identified. According to their abstracts, 10 publications were studied in full text. A scientific taxonomy does not yet exist, but a variety of factors are mentioned. Non-financial conflicts of interest are addressed less accurately and less frequently than financial ones, especially regarding surgical treatment. Since the clinical effect of surgical volume was identified as being relevant, additional 29 respective publications were analysed. This volume-quality relationship causes conflicts of interest for the many surgeons treating a broad spectrum of rare conditions. We present a recommendation that may guide referral of patients requiring complex surgery to centres with a higher volume. CONCLUSIONS: Non-financial conflicts of interest need to be dealt with more accuracy, especially with regard to surgery in rare, complex congenital conditions. The European Reference Networks offer a framework to mitigate these conflicts.

Improved speech and language development after unilateral cochlear implantation in children with a potentially useable contralateral ear.

OBJECTIVES: Increasingly, children are considered for a unilateral cochlear implant (CI), even if the contralateral ear falls outside current audiological guidelines, especially if they are not considered to be reaching their educational potential. Here we present the outcomes of CI in children with potentially useable hearing in the contralateral ear. METHODS: A retrospective case note review was performed for a total of 57 patients. Primary outcome was speech and language (SaL) development, as measured by the Manchester Speech and Language Development Scale (MSLDS) and SaL age equivalent. Secondary outcomes were auditory perception, perceived parental benefit and compliance; respectively measured by Categories of Auditory Performance (CAP), Brief Assessment of Parental Perception (BAPP) and reported use. RESULTS: SaL development improved after CI with a mean pre-operative MSLDS score of 5.8 to a postoperative score of 8.0 (n = 57) and a mean SaL age equivalent of 14 months in a one-year period (n = 14). Furthermore, CAP scores improved from 4.9 to 7.0 (n = 57). Analysis of BAPP scores showed improved quality of life in 18/19 patients (94.7%). With regards to compliance, 50/57 (87.7%) are fulltime users of both their CI and their HA. CONCLUSION: The present study indicates that despite one ear having potentially useable hearing outside national audiological criteria, the majority of participants received benefit from a CI in the poorer hearing ear. We suggest that assessment of each ear separately and treatment with the most appropriate amplification device, has given these children a benefit they may not otherwise have acquired if they only had bilateral HA.

Sox2 is dispensable for primary melanoma and metastasis formation.

Tumor initiation and metastasis formation in many cancers have been associated with emergence of a gene expression program normally active in embryonic or organ-specific stem cells. In particular, the stem cell transcription factor Sox2 is not only expressed in a variety of tumors, but is also required for their formation. Melanoma, the most aggressive skin tumor, derives from melanocytes that during development originate from neural crest stem cells. While neural crest stem cells do not express Sox2, expression of this transcription factor has been reported in melanoma. However, the role of Sox2 in melanoma is controversial. To study the requirement of Sox2 for melanoma formation, we therefore performed CRISPR-Cas9-mediated gene inactivation in human melanoma cells. In addition, we conditionally inactivated Sox2 in a genetically engineered mouse model, in which melanoma spontaneously develops in the context of an intact stroma and immune system. Surprisingly, in both models, loss of Sox2 did neither affect melanoma initiation, nor growth, nor metastasis formation. The lack of a tumorigenic role of Sox2 in melanoma might reflect a distinct stem cell program active in neural crest stem cells and during melanoma formation.

Multifaceted community-based intervention reduces rate of BMI growth in obese Mexican-origin boys.

BACKGROUND: Latino children and youth have some of the highest rates of overweight and obesity. Early intervention is important to prevent future obesity and illness in this population. METHODS: A 3-year, multifaceted intervention was designed to reduce the rate of growth of body mass index (BMI) among Mexican-origin children. Two communities in California's agricultural Central Valley were targeted for intervention and comparison. To assess impact, anthropometric measures of participating children (N = 422) were collected and analysed at baseline and after 1 year of intervention. RESULTS: After 1 year of intervention, triceps skin-fold thickness in girls showed a significant decrease in unadjusted analysis between children in the two communities. In multivariate analysis, a reduction in BMI growth was seen among obese boys in the intervention community (ß-coefficient = -1.94, P = 0.05). Obese boys in the intervention community also had a smaller increase in waist circumference (ß-coefficient = -5.2, P = 0.04) than the comparison community. CONCLUSIONS: These early findings indicate the intervention's effectiveness for preventing BMI growth among obese boys. Longitudinal follow-up is needed to determine the sustainability of results and whether similar results extend to obese girls and overweight boys or girls.

Tissue Expression of Aquaporin 2 Is Correlated to Urine Output and Allograft Function in Sensitized Kidney Transplant Patients.

BACKGROUND: Salt and water disturbances often occur during acute kidney allograft dysfunction that contribute to graft failure, but this condition has been poorly investigated in the alloreactivity setting. We evaluated the tissue expression of aquaporins (AQP1 and AQP2) and the epithelial sodium channel (ENAC) in kidney biopsy specimens from sensitized kidney transplant recipients. METHODS: Eighty-six biopsy specimens from 33 sensitized patients were divided into 3 groups according to clinical context: time-zero (n = 9), protocol (n = 9), and indication (n = 68). The indication biopsy specimens were further divided into 3 subgroups according to the presence of acute tubular necrosis or rejection. Normal kidney tissue samples (n = 6) served as the control specimens. Immmunohistochemical expression of AQP1, AQP2, and ENAC was determined by using image analyzing software. RESULTS: Significantly lower AQP1 expression was observed in the time-zero and indication biopsy specimens with rejection compared with control specimens (P = .03 and P = .04, respectively). AQP2 expression was significantly lower in patients with an indication biopsy specimen compared with control and protocol biopsy specimens (P = .05 and P = .005). For ENAC, a lower expression was noted in the indication biopsy specimens compared with the control specimens (P = .04). Both AQP1 and AQP2 tissue expressions were significantly correlated to urine output (r = 0.45 and r = 0.32; P = .001 and P = .02), and AQP2 was correlated with the glomerular filtration rate estimated by using the Modification of Diet in Renal Disease Study equation at biopsy (r = 0.23; P = .05). CONCLUSIONS: These findings partially confirm previous experimental data showing downregulation of AQP1 expression after ischemia/reperfusion injury and during rejection. AQP2 downregulation seems to be rejection-independent, occurring during deteriorating or poor kidney graft function.

A randomized phase I trial evaluating the effects of inhaled 50-50% N2 O-O2 on remifentanil-induced hyperalgesia and allodynia in human volunteers.

BACKGROUND: Opioids are known to relieve pain, and also aggravate pre-existing hyperalgesia. In animal studies, the N-methyl-d-aspartate-receptor antagonist nitrous oxide (N2 O) was able to prevent hyperalgesia. The present study evaluated the effect of N2 O on hyperalgesia after remifentanil infusion in healthy volunteers. METHODS: Twenty-one healthy volunteers were enrolled in this placebo-controlled cross-over study. Transcutaneous electrical stimulation at high current densities induced spontaneous acute pain and stable areas of hyperalgesia. Each volunteer underwent the following four sessions: (1) 50-50% N2 -O2 and i.v. saline; (2) 50-50% N2 -O2 and i.v. remifentanil 0.1 µg/kg/min; (3) 50-50% N2 O-O2 and i.v. saline; (4) 50-50% N2 O-O2 and i.v. remifentanil 0.1 µg/kg/min. Inhaled gas mixtures lasted for 60 min, i.v. drug administration for 30 min. Visual analogue scale pain intensity, areas of pinprick hyperalgesia and touch-evoked allodynia were assessed repeatedly for 160 min. RESULTS: Data of 19 volunteers were analysed. There were significant time and treatment effects regarding areas of hyperalgesia and allodynia (p < 0.02). The area of hyperalgesia was significantly reduced in the N2 O + remifentanil session compared to the remifentanil session (35.88 ± 22.37 vs. 43.55 ± 18.48 cm(2) , p = 0.004). The area of allodynia was significantly reduced in the N2 O + remifentanil session compared to the remifentanil session (29.95 ± 16.15 vs. 34.80 ± 15.35 cm(2) , p = 0.008). The pain intensity was significantly reduced in the N2 O + remifentanil session compared to the remifentanil session (37.96 ± 12.78 vs. 42.15 ± 13.34 mm, p < 0.0001). CONCLUSIONS: Nitrous oxide significantly reduced hyperalgesia, allodynia and pain intensity aggravated after remifentanil administration in a human volunteer model. WHAT DOES THIS STUDY ADD?: This study brings the evidence that N2 O reduces the remifentanil aggravated secondary hyperalgesia in human volunteers exposed to a well-known model of electrical pain. N2 O was able to oppose the hyperalgesia, the allodynia and the pain intensity consecutive to remifentanil use in this specific pain model.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.

Testing the concurrent validity of a naturalistic upper extremity reaching task.

Point-to-point reaching has been widely used to study upper extremity motor control. We have been developing a naturalistic reaching task that adds tool manipulation and object transport to this established paradigm. The purpose of this study was to determine the concurrent validity of a naturalistic reaching task in a sample of healthy adults. This task was compared to the criterion measure of standard point-to-point reaching. Twenty-eight adults performed unconstrained out-and-back movements in three different directions relative to constant start location along midline using their nondominant arm. In the naturalistic task, participants manipulated a tool to transport objects sequentially between physical targets anchored to the planar workspace. In the standard task, participants moved a digital cursor sequentially between virtual targets, veridical to the planar workspace. In both tasks, the primary measure of performance was trial time, which indicated the time to complete 15 reaches (five cycles of three reaches/target). Two other comparator tasks were also designed to test concurrent validity when components of the naturalistic task were added to the standard task. Spearman's rank correlation coefficients indicated minimal relationship between the naturalistic and standard tasks due to differences in progressive task difficulty. Accounting for this yielded a moderate linear relationship, indicating concurrent validity. The comparator tasks were also related to both the standard and naturalistic task. Thus, the principles of motor control and learning that have been established by the wealth of point-to-point reaching studies can still be applied to the naturalistic task to a certain extent.

A Single-center Experience on the Value of Pancreas Graft Biopsies and HLA Antibody Monitoring After Simultaneous Pancreas-Kidney Transplantation.

BACKGROUND: In simultaneous pancreas-kidney transplantation (SPKT), monitoring of the pancreas allograft is more complex than the kidney allograft due to difficulties in obtaining pancreas histology and weak clinical evidence supporting the role of donor-specific antibodies (DSA). METHODS: We performed a single-center retrospective analysis of all 17 SPKT recipients who underwent a total of 22 pancreas allograft indication biopsies from October 2009 to September 2012. Fifteen patients had at least 2 DSA measurements: pretransplantation and at the time of biopsy. RESULTS: All 7 patients (100%) with post-transplantation DSA-positivity (de novo: n = 6; persistent: n = 1) at biopsy had at least 1 rejection episode either of the pancreas (n = 4) or the kidney (n = 3), with 3 antibody-mediated rejections (AMR). In contrast, only 4 of 8 patients (50%) without post-transplantation DSA had evidence of rejection, with 1 AMR. Findings during pancreas allograft biopsy procedures led to a change of immunosuppressive therapy in 11 of 15 (73%) patients. Patient survival, graft survival, and function were not adversely affected by the presence of post-transplantation DSA. One major and 2 minor procedure-related complications occurred during the pancreas biopsies. CONCLUSIONS: In this small retrospective analysis, pancreas allograft histology provided the most therapeutically relevant information, rather than the kidney histology or DSA monitoring.

[Prehospital analgesia by paramedics in Rhineland-Palatinate : Feasability, analgesic effectiveness and safety of intravenous paracetamol]. / Prähospitale Analgesie durch Rettungsassistenten in Rheinland-Pfalz : Praktikabilität, analgetische Wirkung und Sicherheit bei i.v.-verabreichtem Paracetamol.

BACKGROUND: In contrast to the widespread practice in life-threatening emergencies, delegation of medical pain therapy to paramedics by the medical director  of Emergency Medical Services, EMS, are still the exception in Germany. This is due to the fact that in non-life-threatening situations, the expected benefit and potential side effects of drug therapy have to be carefully weighed. In addition, in Germany federal law generally restricts the administration of opiates to physicians. METHODS: In 2011 the medical directors of EMS in the German state of Rhineland- Palatinate (4 million inhabitants) developed and implemented a standard operating procedure (SOP) for paramedics related to the prehospital parenteral administration of paracetamol for patients with isolated limb trauma. After a 2 h training session and examination, paramedics were authorized to administer 1 g of paracetamol to patients with a pain score > 5 points on an 11-point numerical rating scale (NRS). For purposes of quality management, every administration of paracetamol had to be prospectively documented on a specific electronic mission form. RESULTS: A total of 416 mission forms could be analyzed. After administration of paracetamol the median NRS score decreased from 8 points (interquartile range: 6; 8) to 4 points (interquartile range: 3; 7). In 51.2 % of the patients the pain intensity was reduced by at least 3 NRS points and in 50.5 % of the patients the NRS was less than 5 points after treatment. The extent of pain reduction was positively correlated with the initial NRS value (r = 0.31, p < 0.0001). No serious side effects were noted. The percentage of patients with an initial heart rate > 100/min declined from 14.6 % to 5.2 % after the administration of paracetamol (p < 0.0001), 18.7 % of the patients received paracetamol for trauma not related to the extremities and 7 % of the patients for nontraumatic pain. An emergency physician was involved in 50 % of the EMS missions and 98.6 % of the patients were transported to a hospital for further diagnostics and treatment. CONCLUSION: The prehospital intravenous administration of paracetamol by paramedics to patients with limb trauma is simple, safe and in 50 % of the patients effective in achieving a NRS value < 5; however, further improvements in prehospital pain therapy initiated by paramedics are desirable, especially in patients with an initial NRS value > 7.

Hypoglycin A Content in Blood and Urine Discriminates Horses with Atypical Myopathy from Clinically Normal Horses Grazing on the Same Pasture.

Hypoglycin A (HGA) in seeds of Acer spp. is suspected to cause seasonal pasture myopathy in North America and equine atypical myopathy (AM) in Europe, fatal diseases in horses on pasture. In previous studies, this suspicion was substantiated by the correlation of seed HGA content with the concentrations of toxic metabolites in urine and serum (MCPA-conjugates) of affected horses. However, seed sampling was conducted after rather than during an outbreak of the disease. The aim of this study was to further confirm the causality between HGA occurrence and disease outbreak by seed sampling during an outbreak and the determination of i) HGA in seeds and of ii) HGA and MCPA-conjugates in urine and serum of diseased horses. Furthermore, cograzing healthy horses, which were present on AM affected pastures, were also investigated. AM-pastures in Germany were visited to identify seeds of Acer pseudoplatanus and serum (n = 8) as well as urine (n = 6) from a total of 16 diseased horses were analyzed for amino acid composition by LC-ESI-MS/MS, with a special focus on the content of HGA. Additionally, the content of its toxic metabolite was measured in its conjugated form in body fluids (UPLC-MS/MS). The seeds contained 1.7-319.8 µg HGA/g seed. The content of HGA in serum of affected horses ranged from 387.8-8493.8 µg/L (controls < 10 µg/L), and in urine from 143.8-926.4 µg/L (controls < 10 µg/L), respectively. Healthy cograzing horses on AM-pastures showed higher serum (108.8 ± 83.76 µg/L) and urine concentrations (26.9 ± 7.39 µg/L) compared to control horses, but lower concentrations compared to diseased horses. The range of MCPA-carnitine and creatinine concentrations found in diseased horses in serum and urine were 0.17-0.65 mmol/L (controls < 0.01), and 0.34-2.05 µmol/mmoL (controls < 0.001), respectively. MCPA-glycine levels in urine of cograzing horses were higher compared to controls. Thus, the causal link between HGA intoxication and disease outbreak could be further substantiated, and the early detection of HGA in cograzing horses, which are clinically normal, might be a promising step in prophylaxis.

Prenatal examination of the area and morphology of the atrioventricular valves using four-dimensional ultrasound in normal and abnormal hearts.

OBJECTIVE: Our aim is to evaluate the feasibility to examine the morphology and area of the atrioventricular (AV) valves in normal fetuses and fetuses with cardiac defects using spatiotemporal image correlation (STIC). METHODS: Atrioventricular valves were analyzed longitudinally in STIC volumes of 74 normal fetuses between the 15th and 36th week of pregnancy. The valve area was measured in a rendered view in diastole, the number of valve leaflets in systole. Longitudinal data analysis was performed using linear mixed models. Fifty fetuses with cardiac defects were examined. RESULTS: Examination of 355 STIC volumes of normal fetuses showed in 82.5% sufficient quality. The tricuspid valve leaflets were seen in 200 (68.3%) volumes and the mitral valve leaflets in 219 (74.7%) volumes. The tricuspid valve showed in 61.1% a round, 29.0% rectangle, and 8.9% elliptical shape and the mitral valve in 60.1% round, 28.0% rectangle, and 10.9% elliptical. Regression analysis revealed a positive relationship of the valve area with gestational age (p < 0.0001). Most heart defects with stenosis showed an area below the 5th percentile. CONCLUSION: Prenatal examination of the morphology and area of the AV valves using four-dimensional ultrasound is feasible. A rectangular valve opening is normal, which was visualized in about one third of the normal fetuses.

Clinical characteristics of human immunodeficiency virus patients being referred for liver transplant evaluation: a descriptive cohort study.

BACKGROUND: Liver transplantation (LT) is a treatment option for select human immunodeficiency virus (HIV)-infected patients with advanced liver disease. The aim of this study was to describe LT evaluation outcomes in HIV-infected patients. METHODS: All HIV-infected patients referred for their first LT evaluation at the Mount Sinai Medical Center were included in this retrospective, descriptive cohort study. Multivariable logistic regression was used to identify factors independently associated with listing. RESULTS: Between February 2000 and April 2012, 366 patients were evaluated for LT, with 66 (18.0%) listed for LT and 300 (82.0%) not listed. Fifty-one patients (13.9%) died before completing evaluation and 85 (23.2%) were too early for listing. Reasons patients were declined for listing were psychosocial (15.8%), HIV-related (10.4%), loss to follow-up (9.6%), surgical/medical (6.0%), liver-related (4.4%), patient choice (3.4%), and financial (1.6%). Listed patients were more likely to have hepatocellular carcinoma (HCC) (43.1% vs. 17.1%; P < 0.0001) and less likely to have hepatitis B (6.2% vs. 15.7%; P = 0.04) or a psychiatric history (19.7% vs. 35.2%; P = 0.02) than those not listed. In multivariable analysis, HCC (odds ratio [OR] 5.79; 95% confidence interval [95% CI]: 2.97-11.28), model for end-stage liver disease (MELD) score at referral (OR 1.06; 95% CI 1.01-1.11), and hepatitis B (OR 0.26; 95% CI 0.08-0.79) were associated with listing. CONCLUSION: MELD score and HCC were positive predictors of listing in HIV-infected patients referred for LT evaluation and, therefore, timely referrals are vital in these patients. As MELD is a predictor for death while undergoing evaluation, rapid evaluation should be performed in HIV-infected patients with a higher MELD score.

Traditional food patterns are associated with better diet quality and improved dietary adequacy in Aboriginal peoples in the Northwest Territories, Canada.

BACKGROUND: Traditionally, the Arctic diet has been derived entirely from locally harvested animal and plant species; however, in recent decades, imported foods purchased from grocery stores have become widely available. The present study aimed to examine Inuvialuit, traditional or nontraditional dietary patterns; nutrient density of the diet; dietary adequacy; and main food sources of energy and selected nutrient intakes. METHODS: This cross-sectional study used a culturally appropriate quantitative food frequency questionnaire to assess diet. Traditional and nontraditional eaters were classified as those consuming more or less than 300 g of traditional food daily. Nutrient densities per 4184 kJ (1000 kcal) were determined. Dietary adequacy was determined by comparing participants' nutrient intakes with the Dietary Reference Intakes. RESULTS: The diet of nontraditional eaters contained, on average, a lower density of protein, niacin, vitamin B12 , iron, selenium, zinc, omega-3 fatty acids (P ≤ 0.0001), vitamin B6 , potassium, thiamin, pantothenic acid (P ≤ 0.001), riboflavin and magnesium (P ≤ 0.05). Inadequate nutrient intake was more common among nontraditional eaters for calcium, folate, vitamin C, zinc, thiamin, pantothenic acid, vitamin K, magnesium, potassium and sodium. Non-nutrient-dense foods (i.e. high fat and high sugar foods) contributed to energy intake in both groups, more so among nontraditional eaters (45% versus 33%). Traditional foods accounted for 3.3% and 20.7% of total energy intake among nontraditional and traditional eaters, respectively. CONCLUSIONS: Diet quality and dietary adequacy were better among Inuvialuit who consumed more traditional foods. The promotion of traditional foods should be incorporated in dietary interventions for this population.

Flavor-enhancing properties of mushrooms in meat-based dishes in which sodium has been reduced and meat has been partially substituted with mushrooms.

The effects of beef substitution with crimini or white mushrooms (Agaricus bisporus) on the flavor profiles of carne asada and beef taco blends were measured with a descriptive analysis panel. Sensory mitigation of sodium reduction through the incorporation of mushrooms was also investigated in the taco blends. The substitution of beef with mushrooms in the carne asada did not alter the overall flavor strength of the dish, but the incorporation of 50% or 80% ground mushroom in the beef taco blend did enhance its overall flavor as well as mushroom, veggie, onion, garlic and earthy flavors, and umami and sweet tastes. Overall flavor intensity of the 25% reduced-salt version of the 80% mushroom taco blend matched that of the full-salt versions of the 100% and 50% beef formulations, thus indicating that the substitution of 80% of the meat with mushrooms did mitigate the 25% sodium reduction in terms of the overall flavor impact of the dish, even if it did not quite compensate for the reduction in salty taste. This proof-of-concept study for the Healthy Flavors Research Initiative indicates that because of their flavor-enhancing umami principles, mushrooms can be used as a healthy substitute for meat and a mitigating agent for sodium reduction in meat-based dishes without loss of overall flavor.

Pituitary function in patients with hereditary haemochromatosis.

Haemochromatosis may impair the function of endocrine organs, amongst others the pituitary gland. It was the aim of this study to determine pituitary function in adult patients with genetically defined hereditary haemochromatosis in a prospective diagnostic study using a standardised stimulation test. Therefore, 22 patients (7 females, 15 males; age at diagnosis of haemochromatosis 48.1 ± 7.9 years; age at study inclusion 50.7 ± 7.7 years) with genetically defined hereditary haemochromatosis were investigated by a combined pituitary stimulation test (CRH, GHRH/arginine, GnRH, TRH). In 11 patients (50% of the study population; 2 females, 9 males), pituitary insufficiencies were detected [isolated corticotrophic insufficiency (peak cortisol < 181.25 µg/l/500 nmol/l) n=10 (2 females, 8 males); combined corticotrophic and borderline gonadotrophic insufficiency (basal testosterone 2.4-3.0 µg/l without basal LH-elevation) in 1 male]. Somatotrophic pituitary insufficiencies were not found. IFG-1 concentrations below -2 standard deviations in 7 patients (32%) may be attributed to impaired hepatic IGF-1 synthesis. Hypopituitarism, particularly corticotrophic insufficiency, seems to be prevalent in a considerable number of middle-aged patients with hereditary haemochromatosis. Despite normal somatotrophic function, low IGF-1 serum concentrations may be found in a subgroup of haemochromatosis patients.

Potassium restores vasorelaxation of resistance arterioles in non-hypertensive DOCA/salt fed mice.

BACKGROUND: Potassium-enriched diets exert renal and cardiovascular protective effects, but the underlying mechanisms are largely unknown. METHODS: Using the dorsal skinfold chamber model for intravital microscopy, we examined endothelium-dependent vasorelaxation of precapillary resistance arterioles in response to acetylcholine or the NO donor SNAP in awake mice. Experiments were performed in uni-nephrectomized one renin gene (Ren-1c) C57BL/6 mice (control group) and in mice having received a continuous administration of deoxycorticosterone acetate and a dietary supplementation of 1% sodium chloride for 8 weeks (DOCA/salt group). An additional group of DOCA/salt treated animals received a dietary supplement of 0.4% KCl for 3 weeks prior to the experiments (DOCA/salt + potassium group). RESULTS: DOCA/salt treatment for 8 weeks resulted in hypokalemia, but blood pressure remained unchanged. In DOCA/salt mice, relaxation of resistance arterioles was blunted in response to acetylcholine, and to a lesser extent to SNAP, suggesting endothelial dysfunction. Endothelium-dependent vasorelaxation was restored by the potassium-enriched diet. CONCLUSION: This study is the first to demonstrate a protective effect of potassium on endothelium-dependent vasorelaxation in the absence of confounding anti-hypertensive effects, as observed in most animal models and the clinical situation. We propose that the known cardio- and nephro-protective effects of potassium might - at least in part - be mediated by the salutary effects on endothelium-dependent arteriolar relaxation.

High resolution ultrasound including elastography and contrast-enhanced ultrasound (CEUS) for early detection and characterization of liver lesions in the humanized tumor mouse model.

PURPOSE: In this study we investigated the sensitivity of high resolution ultrasound (HRU) in the detection of small liver tumors and its microcirculation in a humanized tumor mouse model (HTM). These mice develop a complete human immune system and human breast cancer growth in the liver which allows the investigation of antibody based immunotherapies under human like conditions. METHOD: HTM were generated by the co-transplantation of human breast cancer cells and human hematopoietic stem cells. HRU, Doppler sonography (CCDS), contrast enhanced ultrasound (CEUS) and color-coded elastography were performed on all HTM and confirmed by histopathological assessment. RESULTS: Using HRU and CEUS, noncystic solid liver lesions between 2 and 11 mm (mean 3.5 mm) size were detectable in HTM. Granulomatous areas were identified by B-scan imaging, showing areas of higher stiffness in elastography and areas without contrast media uptake in the late phase (CEUS). In addition, CEUS detected capillary microcirculation of benign and malignant liver lesions smaller than 10 mm. CONCLUSION: Beyond human breast cancer HTM additionally developed small parenchymal liver lesions, which could be characterized by HRU in combination with CEUS and elastography in-vivo. Nevertheless, the defined diagnoses of solid liver lesions less than 5 mm require confirmation by histopathology.