A Novel HPLC Method for the Concurrent Analysis and Quantitation of Seven Water-Soluble Vitamins in Biological Fluids (Plasma and Urine): A Validation Study and Application

An HPLC method was developed and validated for the concurrent detection and quantitation of seven water-soluble vitamins (C, B1, B2, B5, B6, B9, B12) in biological matrices (plasma and urine). Separation was achieved at 30°C on a reversed-phase C18-A column using combined isocratic and linear gradient elution with a mobile phase consisting of 0.01% TFA aqueous and 100% methanol. Total run time was 35 minutes. Detection was performed with diode array set at 280 nm. Each vitamin was quantitatively determined at its maximum wavelength. Spectral comparison was used for peak identification in real samples (24 plasma and urine samples from abstinent alcohol-dependent males). Interday and intraday precision were <4% and <7%, respectively, for all vitamins. Recovery percentages ranged from 93% to 100%

Awareness of, and participation with, user-created alcohol promotion, and the association with higher-risk drinking in young adults

User-created alcohol promotion refers to the content distributed through new media which intends to promote consumption, but independent of commercial digital marketing. This study explores exposure to such user-created alcohol promotion and the association with higher-risk drinking in a sample of young adults in the United Kingdom. An online cross-sectional survey with 18-25 year olds (n = 405) was used to measure awareness of, and participation with, 11 forms of user-created alcohol promotion. Higher-risk drinking was measured through the Alcohol Use Disorders Identification Test &ndash; Consumption (AUDIT-C). On average, participants were aware of 7.48 user-created alcohol promotion channels and had participated with 4.36. A hierarchical logistic regression highlighted a positive association between exposure to user-created alcohol promotion and higher-risk consumption, with participation (AOR = 1.64) having a stronger association with higher-risk consumption than awareness (AOR = 1.19). The results suggest that young adults are aware of, and participating with, a cumulative range of user-created alcohol promotion, both within and beyond social media. Further research is required to understand whether this association with higher-risk drinking is causal, the links between user-created alcohol promotion and commercial marketing, and the wider utility of user-created content to influence health behaviours in young adults

Effect of two behavioural 'nudging' interventions on management decisions for low back pain: A randomised vignette-based study in general practitioners

Objective €Nudges' are subtle cognitive cues thought to influence behaviour. We investigated whether embedding nudges in a general practitioner (GP) clinical decision support display can reduce low-value management decisions. Methods Australian GPs completed four clinical vignettes of patients with low back pain. Participants chose from three guideline-concordant and three guideline-discordant (low-value) management options for each vignette, on a computer screen. A 2×2 factorial design randomised participants to two possible nudge interventions: €partition display' nudge (low-value options presented horizontally, high-value options listed vertically) or €default option' nudge (high-value options presented as the default, low-value options presented only after clicking for more). The primary outcome was the proportion of scenarios where practitioners chose at least one of the low-value care options. Results 120 GPs (72% male, 28% female) completed the trial (n=480 vignettes). Participants using a conventional menu display without nudges chose at least one low-value care option in 42% of scenarios. Participants exposed to the default option nudge were 44% less likely to choose at least one low-value care option (OR 0.56, 95%CI 0.37 to 0.85; p=0.006) compared with those not exposed. The partition display nudge had no effect on choice of low-value care (OR 1.08, 95%CI 0.72 to 1.64; p=0.7). There was no interaction between the nudges (OR 0.94, 95% CI 0.41 to 2.15; p=0.89). Interpretation A default option nudge reduced the odds of choosing low-value options for low back pain in clinical vignettes. Embedding high value options as defaults in clinical decision support tools could improve quality of care. More research is needed into how nudges impact clinical decision-making in different contexts

The Seeds of Exclusion

First paragraph: It is in the context of all the factors relating to the social, physical and mental wellbeing of Britain in 2008 that The Salvation Army presents The Seeds of Exclusion report. The research findings must be read in the light of the additional pressures we have identified which may be brought to bear on individuals already living in a society which is becoming increasingly fragmented, chaotic and stressful. The Salvation Army hopes its contribution to this ongoing debate will begin to inform us all, including Government, on how we can avoid the mistakes of the past and begin to mend society

Nutritional deficiencies in homeless persons with problematic drinking:A systematic review

BACKGROUND: A significant proportion of homeless people drink alcohol excessively and this can lead to malnutrition and consequent medical problems. The aim of this review was to assess the evidence on the range of nutritional deficiencies in the homeless problem-drinking populations. METHODS: We conducted a comprehensive search of nine scientific literature databases and 13 grey literature sources. We included studies of any design that included homeless population with problem-drinking and reported measures of nutritional deficiencies in urine or blood. Study selection and data extraction was done by one reviewer and checked by another. Data on malnutrition profile were summarized narratively. RESULTS: We found nine studies reporting nutritional deficiencies in homeless populations with problem-drinking. The oldest study was from the 1950s and the most recent from 2013. The following nutrients were reported across studies: vitamins B1, B2, B6, B9, B12, C, A, and E; haemoglobin; and albumin. The most common deficiencies reported were of vitamin B1 (prevalence of deficiency was 0, 2, 6, 45, and 51% in five studies) and vitamin C (29, 84, and 95% in three studies). None of the studies were assessed to be at a low risk of bias. CONCLUSIONS: The limited, low quality and relatively old evidence suggests that homeless people who drink heavily may be deficient in vitamin C, thiamine, and other nutrients. New, well conducted studies are needed in order to optimally inform public health interventions aimed at improving deficiencies in this population

The effects of nitroxyl (HNO) on soluble guanylate cyclase activity: interactions at ferrous heme and cysteine thiols

It has been previously proposed that nitric oxide (NO) is the only biologically relevant nitrogen oxide capable of activating the enzyme soluble guanylate cyclase (sGC). However, recent reports implicate HNO as another possible activator of sGC. Herein, we examine the affect of HNO donors on the activity of purified bovine lung sGC and find that, indeed, HNO is capable of activating this enzyme. Like NO, HNO activation appears to occur via interaction with the regulatory ferrous heme on sGC. Somewhat unexpectedly, HNO does not activate the ferric form of the enzyme. Finally, HNO-mediated cysteine thiol modification appears to also affect enzyme activity leading to inhibition. Thus, sGC activity can be regulated by HNO via interactions at both the regulatory heme and cysteine thiols

Chronic kidney disease in public renal practices in Queensland, Australia, 2011–2018

Aim: To describe adults with (non-dialysis) chronic kidney disease (CKD) in nine public renal practice sites in the Australian state of Queensland. Methods: 7,060 persons were recruited to a CKD Registry in May 2011 and until start of kidney replacement therapy (KRT), death without KRT or June 2018, for a median period of 3.4 years. Results: The cohort comprised 7,060 persons, 52% males, with a median age of 68 yr; 85% had CKD stages 3A to 5, 45.4% were diabetic, 24.6% had diabetic nephropathy, and 51.7% were obese. Younger persons mostly had glomerulonephritis or genetic renal disease, while older persons mostly had diabetic nephropathy, renovascular disease and multiple diagnoses. Proportions of specific renal diagnoses varied >2-fold across sites. Over the first year, eGFR fell in 24% but was stable or improved in 76%. Over follow up, 10% started KRT, at a median age of 62 yr, most with CKD stages 4 and 5 at consent, while 18.8% died without KRT, at a median age of 80 yr. Indigenous people were younger at consent and more often had diabetes and diabetic kidney disease and had higher incidence rates of KRT. Conclusion: The spectrum of characteristics in CKD patients in renal practices is much broader than represented by the minority who ultimately start KRT. Variation in CKD by causes, age, site and Indigenous status, the prevalence of obesity, relative stability of kidney function in many persons over the short term, and differences between those who KRT and die without KRT are all important to explore

Hospitalizations Among Adults With CKD in Public Renal Specialty Practices: A Retrospective Study From Queensland, Australia

Rationale & Objective: Little is known about hospital admissions in nondialysis patients with chronic kidney disease (CKD) before death or starting kidney replacement therapy (KRT). Study Design: Retrospective observational cohort study. Setting & Participants: Hospitalizations among 7,201 patients with CKD from 10 public renal clinics in Queensland (QLD), enrolled in the CKD.QLD registry starting in May 2011, were followed for 25,496.34 person-years until they started receiving KRT or died, or until June 30, 2018. Predictors: Demographic and clinical characteristics of patients with CKD. Outcomes: Hospital admissions. Analytical Approach: We evaluated the association of demographic and clinical features with hospitalizations, length of hospital stay, and cost. Results: Approximately 81.5% of the patients were admitted at least once, with 42,283 admissions, costing Australian dollars (AUD) 231 million. The average number of admissions per person-year was 1.7, and the cost was AUD 9,060, 10 times and 2 times their Australian averages, respectively. Single (1-day) admissions constituted 59.2% of all the hospital episodes, led by neoplasms (largely chemotherapy), anemia, CKD-related conditions and eye conditions (largely cataract extractions), but only 14.8% of the total costs. Approximately 41% of admissions were >1-day admissions, constituting 85.2% of the total costs, with cardiovascular conditions, respiratory conditions, CKD-related conditions, and injuries, fractures, or poisoning being the dominant causes. Readmission within 30 days of discharge constituted >42% of the admissions and 46.8% costs. Admissions not directly related to CKD constituted 90% of the admissions and costs. More than 40% of the admissions and costs were through the emergency department. Approximately 19% of the hospitalized patients and 27% of the admissions did not have kidney disease mentioned as either principal or associate causes. Limitations: Variable follow-up times because of different dates of consent. Conclusions: The hospital burden of patients with CKD is mainly driven by complex multiday admissions and readmissions involving comorbid conditions, which may not be directly related to their CKD. Strategies to prevent these complex admissions and readmissions should minimize hospital costs and outcomes. Plain-Language Summary: We analyzed primary causes, types, and costs of hospitalizations among 7,201 patients with chronic kidney disease (CKD) from renal speciality clinics across Queensland, Australia, over an average follow-up of 3.54 years. The average annual cost per person was $9,060, and was the highest in those with more advanced CKD, higher age, and with diabetes. More than 85% of costs were driven by more complex hospitalizations with longer length of stay. Cardiovascular disease was the single largest contributor for hospitalizations, length of hospital stay, and total costs. Readmission within 30 days of discharge, particularly for the same disorder, and multiday admissions should be the main targets for mitigation of hospital costs in this population

The Putative bZIP Transcripton Factor BzpN Slows Proliferation and Functions in the Regulation of Cell Density by Autocrine Signals in Dictyostelium

The secreted proteins AprA and CfaD function as autocrine signals that inhibit cell proliferation in Dictyostelium discoideum, thereby regulating cell numbers by a negative feedback mechanism. We report here that the putative basic leucine zipper transcription factor BzpN plays a role in the inhibition of proliferation by AprA and CfaD. Cells lacking BzpN proliferate more rapidly than wild-type cells but do not reach a higher stationary density. Recombinant AprA inhibits wild-type cell proliferation but does not inhibit the proliferation of cells lacking BzpN. Recombinant CfaD also inhibits wild-type cell proliferation, but promotes the proliferation of cells lacking BzpN. Overexpression of BzpN results in a reduced cell density at stationary phase, and this phenotype requires AprA, CfaD, and the kinase QkgA. Conditioned media from high-density cells stops the proliferation of wild-type but not bzpN− cells and induces a nuclear localization of a BzpN-GFP fusion protein, though this localization does not require AprA or CfaD. Together, the data suggest that BzpN is necessary for some but not all of the effects of AprA and CfaD, and that BzpN may function downstream of AprA and CfaD in a signal transduction pathway that inhibits proliferation