Association between risk of dementia and very late-onset schizophrenia-like psychosis: a Swedish population-based cohort study.

BACKGROUND: Although the incidence of psychotic disorders among older people is substantial, little is known about the association with subsequent dementia. We aimed to examine the rate of dementia diagnosis in individuals with very late-onset schizophrenia-like psychosis (VLOSLP) compared to those without VLOSLP. METHODS: Using Swedish population register data, we established a cohort of 15 409 participants with VLOSLP matched by age and calendar period to 154 090 individuals without VLOSLP. Participants were born between 1920 and 1949 and followed from their date of first International Classification of Diseases [ICD], Revisions 8-10 (ICD-8/9/10) non-affective psychotic disorder diagnosis after age 60 years old (or the same date for matched participants) until the end of follow-up (30th December 2011), emigration, death, or first recorded ICD-8/9/10 dementia diagnosis. RESULTS: We found a substantially higher rate of dementia in individuals with VLOSLP [hazard ratio (HR): 4.22, 95% confidence interval (95% CI) 4.05-4.41]. Median time-to-dementia-diagnosis was 75% shorter in those with VLOSLP (time ratio: 0.25, 95% CI 0.24-0.26). This association was strongest in the first year following VLOSLP diagnosis, and attenuated over time, although dementia rates remained higher in participants with VLOSLP for up to 20 years of follow-up. This association remained after accounting for potential misdiagnosis (2-year washout HR: 2.22, 95% CI 2.10-2.36), ascertainment bias (HR: 2.89, 95% CI 2.75-3.04), and differing mortality patterns between groups (subdistribution HR: 2.89, 95% CI 2.77-3.03). CONCLUSIONS: Our findings demonstrate that individuals with VLOSLP represent a high-risk group for subsequent dementia. This may be due to early prodromal changes for some individuals, highlighting the importance of ongoing symptom monitoring in people with VLOSLP.

Socio-economic, demographic, and clinical correlates of poor glycaemic control within insulin regimens among children with Type 1 diabetes: the SEARCH for Diabetes in Youth Study.

AIM: To examine the distribution and association of sociodemographic, adherence, and barriers-to-care factors in relation to glycaemic control within insulin regimens in US children with Type 1 diabetes in the SEARCH for Diabetes in Youth Study. METHODS: Self- or parent-reported data from 1095 children with Type 1 diabetes aged 10-17 years were collected on insulin regimen, sociodemographics, diabetes self-management, diabetes-related family conflict and barriers to care. Multivariable logistic regression analysis identified poor glycaemic control correlates within each insulin regimen. RESULTS: Participants included 694 children on insulin pump therapy, 188 receiving basal-bolus injections, and 213 on a mixed insulin regimen. Of these, 28.5%, 45.2% and 51.2%, respectively, had poor glycaemic control [HbA1c ≥ 80 mmol/mol (9.5%)]. Family conflict between parent and child regarding diabetes management was the only factor significantly associated with poor glycaemic control in all insulin regimens (insulin pump, P≤ 0.0001; basal-bolus injections, P=0.0002; mixed insulin regimen, P=0.0103). For children on insulin pump, poor control was significantly associated with non-white race (P=0.0008), living in multiple households (P=0.0331), having Medicaid insurance (P=0.0090), and decreased insulin adherence (P<0.0001). For children on a mixed insulin regimen, living in multiple households (P=0.0256) and not spending enough time with healthcare provider (P=0.0058) correlated with poor control. CONCLUSIONS: A high percentage of US children with Type 1 diabetes had poor glycaemic control, especially those not using an insulin pump. Early identification of children with risk factors associated with poor glycaemic control within insulin regimens and addressing diabetes-related family conflict may allow interventions to improve diabetes management.

Novel loci associated with usual sleep duration: the CHARGE Consortium Genome-Wide Association Study.

Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.

Aldosterone deficiency prevents high-fat-feeding-induced hyperglycaemia and adipocyte dysfunction in mice.

AIMS/HYPOTHESIS: Obesity is associated with aldosterone excess, hypertension and the metabolic syndrome, but the relative contribution of aldosterone to obesity-related complications is debated. We previously demonstrated that aldosterone impairs insulin secretion, and that genetic aldosterone deficiency increases glucose-stimulated insulin secretion in vivo. We hypothesised that elimination of endogenous aldosterone would prevent obesity-induced insulin resistance and hyperglycaemia. METHODS: Wild-type and aldosterone synthase-deficient (As (-/-)) mice were fed a high-fat (HF) or normal chow diet for 12 weeks. We assessed insulin sensitivity and insulin secretion using clamp methodology and circulating plasma adipokines, and examined adipose tissue via histology. RESULTS: HF diet induced weight gain similarly in the two groups, but As (-/-) mice were protected from blood glucose elevation. HF diet impaired insulin sensitivity similarly in As (-/-) and wild-type mice, assessed by hyperinsulinaemic-euglycaemic clamps. Fasting and glucose-stimulated insulin were higher in HF-fed As (-/-) mice than in wild-type controls. Although there was no difference in insulin sensitivity during HF feeding in As (-/-) mice compared with wild-type controls, fat mass, adipocyte size and adiponectin increased, while adipose macrophage infiltration decreased. HF feeding significantly increased hepatic steatosis and triacylglycerol content in wild-type mice, which was attenuated in aldosterone-deficient mice. CONCLUSIONS/INTERPRETATION: These studies demonstrate that obesity induces insulin resistance independently of aldosterone and adipose tissue inflammation, and suggest a novel role for aldosterone in promoting obesity-induced beta cell dysfunction, hepatic steatosis and adipose tissue inflammation.

Dietary practices in pyridoxine non-responsive homocystinuria: a European survey.

BACKGROUND: Within Europe, the management of pyridoxine (B6) non-responsive homocystinuria (HCU) may vary but there is limited knowledge about treatment practice. AIM: A comparison of dietetic management practices of patients with B6 non-responsive HCU in European centres. METHODS: A cross-sectional audit by questionnaire was completed by 29 inherited metabolic disorder (IMD) centres: (14 UK, 5 Germany, 3 Netherlands, 2 Switzerland, 2 Portugal, 1 France, 1 Norway, 1 Belgium). RESULTS: 181 patients (73% >16 years of age) with HCU were identified. The majority (66%; n=119) were on dietary treatment (1-10 years, 90%; 11-16 years, 82%; and >16 years, 58%) with or without betaine and 34% (n=62) were on betaine alone. The median natural protein intake (g/day) on diet only was, by age: 1-10 years, 12 g; 11-16 years, 11 g; and >16 years, 45 g. With diet and betaine, median natural protein intake (g/day) by age was: 1-10 years, 13 g; 11-16 years, 20 g; and >16 years, 38 g. Fifty-two percent (n=15) of centres allocated natural protein by calculating methionine rather than a protein exchange system. A methionine-free l-amino acid supplement was prescribed for 86% of diet treated patients. Fifty-two percent of centres recommended cystine supplements for low plasma concentrations. Target treatment concentrations for homocystine/homocysteine (free/total) and frequency of biochemical monitoring varied. CONCLUSION: In B6 non-responsive HCU the prescription of dietary restriction by IMD centres declined with age, potentially associated with poor adherence in older patients. Inconsistencies in biochemical monitoring and treatment indicate the need for international consensus guidelines.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

An examination of mindfulness on Mu suppression and pain empathy and its relation to trait empathy.

There have been multiple benefits reported from the practice of mindfulness meditation. Recently social functioning, including empathy, has emerged as one such possible benefit. However, the literature is mixed and it is unknown if mindfulness has an effect on the neural mechanism involved in empathy. Therefore, we conducted a large-scale experimental study involving over 100 participants that were either enrolled in a behavioral or EEG experiment to examine pain empathy and mu suppression, respectively. We also measured state and trait mindfulness and trait empathy. Results did not show a change in pain empathy or mu suppression in response to an acute mindfulness manipulation. However, pain empathy responses were able to be predicted significantly better when the component of state mindfulness involving decentering was incorporated into a regression model compared to trait empathy alone. Also, trait empathy was related to trait mindfulness. Collectively, state decentering may be involved in increased pain empathy, while trait mindfulness appears more related to general trait empathy. Further research is warranted to better understand the potential benefit a brief mindfulness meditation may produce in the realm of brain activity and social functioning.

The incidence of psychotic disorders in the Republic of Ireland: a systematic review.

OBJECTIVES: Despite a substantial epidemiological literature on the incidence of psychotic disorders in Ireland, no systematic review has previously been undertaken. Such evidence can help inform understanding of need for psychosis care. METHODS: We conducted a prospectively registered systematic review (PROSPERO: CRD42021245891) following PRISMA guidelines. We searched four databases (Medline, PsycInfo, Web of Science, Embase) for papers containing incidence data on non-organic psychotic disorders, in people 16-64 years, published between 1950 and 2021 in the general adult population. We conducted duplicate screening, risk of bias assessments, and extracted data to a standardised template. We undertook a narrative synthesis for each major diagnostic outcome. Random effects meta-analyses were conducted for comparisons with ≥5 incidence rates. RESULTS: Our search yielded 1975 non-duplicate citations, of which 23 met inclusion criteria, containing incidence data ascertained between 1974 and 2016 (median study quality: 5/8; interquartile range: 4-6). Incidence of all psychotic disorders (N = 4 studies) varied from 22.0 (95%CI: 17.3-28.0) in Dublin to 34.1 per 100,000 person-years (95%CI: 31.0-37.5) in Cavan and Monaghan. The pooled incidence of schizophrenia (N = 6 studies, N = 8 settings) was 20.0 per 100,000 person-years, though with imprecision around this estimate (95%CI: 10.6-37.5; I2: 97.6%). Higher rates of most outcomes were observed in men. There was consistent evidence of raised rates in more deprived and fragmented social environments, but no clear pattern by rural-urban status. CONCLUSIONS: Patterns of incidence of psychotic disorders in Ireland are broadly consistent with the wider literature from the Global North. Findings could help identify populations at higher risk of psychosis in Ireland.

Mapping cancer risk in southwestern Ontario with changing census boundaries.

Mapping disease risk often involves working with data that have been spatially aggregated to census regions or postal regions, either for administrative reasons or confidentiality. When studying rare diseases, data must be collected over a long time period in order to accumulate a meaningful number of cases. These long time periods can result in spatial boundaries of the census regions changing over time, as is the case with the motivating example of exploring the spatial structure of mesothelioma lung cancer risk in Lambton County and Middlesex County of southwestern Ontario, Canada. This article presents a local-EM kernel smoothing algorithm that allows for the combining of data from different spatial maps, being capable of modeling risk for spatially aggregated data with time-varying boundaries. Inference and uncertainty estimates are carried out with parametric bootstrap procedures, and cross-validation is used for bandwidth selection. Results for the lung cancer study are shown and discussed.

Dietary management of urea cycle disorders: UK practice.

BACKGROUND: There is no published data describing UK dietary management of urea cycle disorders (UCD). The present study describes dietary practices in UK inherited metabolic disorder (IMD) centres. METHODS: Cross-sectional data from 16 IMD centres were collected by a questionnaire describing the management of UCD patients on prescribed protein-restricted diets. RESULTS: One hundred and seventy-five patients [N-acetylglutamate synthase deficiency, n = 3; carbamoyl phosphate synthase deficiency (CPS), n = 8; ornithine transcarbamoylase deficiency (OTC), n = 75; citrullinaemia, n = 41; argininosuccinic aciduria (ASA), n = 36; arginase deficiency, n = 12] were reported; 70% (n = 123) aged 0-16 years; 30% (n = 52) >16 years. Prescribed median protein intake decreased with age (0-6 months: 2 g kg(-1) day(-1); 7-12 months: 1.6 g kg(-1) day(-1); 1-10 years: 1.3 g kg(-1) day(-1); 11-16 years: 0.9 g kg(-1) day(-1) and >16 years: 0.8 g kg(-1) day(-1)) with little variation between disorders. Adult protein prescription ranged 0.4-1.2 g kg(-1) day(-1) (40-60 g day(-1)). In the previous 2 years, 30% (n = 53) were given essential amino acid supplements (EAAs) (CPS, n = 2; OTC, n = 20; citrullinaemia, n = 15; ASA, n = 7; arginase deficiency, n = 9). EAAs were prescribed for low plasma quantitative essential amino acids (n = 13 centres); inadequate natural protein intake (n = 11) and poor metabolic control (n = 9). From diagnosis, one centre prescribed EAAs for all patients and one centre for severe defects only. Only 3% (n = 6) were given branch chain amino acid supplements. Enteral feeding tubes were used by 25% (n = 44) for feeds and 3% (n = 6) for medications. Oral energy supplements were prescribed in 17% (n = 30) of cases. CONCLUSIONS: In the UK, protein restriction based on World Health Organization 'safe intakes of protein', is the principle dietary treatment for UCD. EAA supplements are prescribed mainly on clinical need. Multicentre collaborative research is required to define optimal dietary treatments.

Intrapulmonary arteries respond to serotonin and adenosine triphosphate in broiler chickens susceptible to idiopathic pulmonary arterial hypertension.

This study examined factors contributing to increased vascular resistance and plexiform lesion formation in broiler chickens susceptible to idiopathic pulmonary arterial hypertension (IPAH). A diet supplemented with excess tryptophan (high-Trp diet), the precursor for serotonin, was used to accelerate the development of IPAH. Broilers fed the high-Trp diet had higher pulmonary arterial pressures than broilers fed the control diet, and plexiform lesion incidences tended to be higher (P = 0.11) in the high-Trp group than in the control group at 30 d of age. The intrapulmonary arteries were assessed for vasoconstriction in response to serotonin and adenosine triphosphate (ATP) and for activities of key metabolic enzymes for serotonin and ATP. The pulmonary artery (defined as the first major branch of the pulmonary artery inside the lung) and the primary pulmonary arterial rami (defined as the second major branch of the pulmonary artery inside the lung) both exhibited vasoconstriction in response to serotonin and ATP. This is the first study to demonstrate purinergic-mediated vasoconstriction in intrapulmonary arteries from broilers. Arteriole responsiveness did not differ between broilers fed the control diet or the high-Trp diet. Therefore, the high-Trp diet enhanced the development of IPAH but did not affect the artery's sensitivity to serotonin or ATP. Monoamine oxidase activity, responsible for the breakdown of serotonin, was severely impaired in pulmonary arteries from broilers in the high-Trp group. Accordingly, serotonin may persist longer and elicit an amplified response in broilers fed the high-Trp diet.

Use of a long-chain triglyceride-restricted/medium-chain triglyceride-supplemented diet in a case of malonyl-CoA decarboxylase deficiency with cardiomyopathy.

Malonyl coenzyme A (CoA) decarboxylase (EC 4.1.1.9, MCD) deficiency, or malonic aciduria, is a rare inborn error of metabolism characterised by a variable phenotype of developmental delay, seizures, cardiomyopathy and acidosis. There is no consensus for dietary treatment in this condition. This case describes the effect of a long-chain triglyceride (LCT)-restricted/medium-chain triglyceride (MCT)-supplemented diet upon the progress of an affected child. A full-term Asian girl of birth weight 3590 g was screened for malonic aciduria after birth due to a positive family history. She had elevated urine malonic and methylmalonic acids and was presumably homozygous for a deleterious mutation in the MLYCD gene. Her echocardiography showed mild cardiomyopathy at 0.5 months of age, but heart function was good. She was treated with carnitine 100 mg/kg per day and continued a high-energy formula feed, as her growth was slow. At 3 months of age, echocardiography showed deteriorating cardiac function with a fractional shortening of 18%. She started an angiotensin-converting enzyme (ACE) inhibitor (Captopril). Over the next few months, her diet was altered to comprise 1.9% energy from LCT, 25% from MCT and the remainder carbohydrate. Cardiac function improved and was optimal at 23 months of age, with a fractional shortening of 28% and good systolic function. During a period of low MCT intake, her cardiac function was noted to deteriorate. This reversed and stabilised following reinstatement of the diet. This case of malonic aciduria with cardiomyopathy demonstrates improvement in cardiac function attributable to LCT-restricted/MCT-supplemented diet.

Numerical simulations of a falling film on the inner surface of a rotating cylinder.

A flow in which a thin film falls due to gravity on the inner surface of a vertical, rotating cylinder is investigated. This is performed using two-dimensional (2D) and 3D direct numerical simulations, with a volume-of-fluid approach to treat the interface. The problem is parameterized by the Reynolds, Froude, Weber, and Ekman numbers. The variation of the Ekman number (Ek), defined to be proportional to the rotational speed of the cylinder, has a strong effect on the flow characteristics. Simulations are conducted over a wide range of Ek values (0≤Ek≤484) in order to provide detailed insight into how this parameter influences the flow. Our results indicate that increasing Ek, which leads to a rise in the magnitude of centrifugal forces, produces a stabilizing effect, suppressing wave formation. Key flow features, such as the transition from a 2D to a more complex 3D wave regime, are influenced significantly by this stabilization and are investigated in detail. Furthermore, the imposed rotation results in distinct flow characteristics such as the development of angled waves, which arise due to the combination of gravitationally and centrifugally driven motion in the axial and azimuthal directions, respectively. We also use a weighted residuals integral boundary layer method to determine a boundary in the space of Reynolds and Ekman numbers that represents a threshold beyond which waves have recirculation regions.

Remote CB1 receptor antagonist administration reveals multiple sites of tonic and phasic endocannabinoid neuroendocrine regulation.

Endogenous cannabinoids (endocannabinoids, eCB) are expressed throughout the body and contribute to regulation of the hypothalamo-pituitary-adrenal (HPA) axis and general stress reactivity. This study assessed the contributions of CB1 receptors (CB1R) in the modulation of basal and stress-induced neural and HPA axis activities. Catheterized adult male rats were placed in chambers to acclimate overnight, with their catheters connected and exteriorized from the chambers for relatively stress-free remote injections. The next morning, the CB1R antagonist AM251 (1 or 2 mg/kg) or vehicle was administered, and 30 min later, rats were exposed to loud noise stress (30 min) or no noise (basal condition). Blood, brains, pituitary and adrenal glands were collected immediately after the procedures for analysis of c-fos and CB1R mRNAs, corticosterone (CORT) and adrenocorticotropin hormone (ACTH) plasma levels. Basally, CB1R antagonism induced c-fos mRNA in the basolateral amygdala (BLA) and auditory cortex (AUD) and elevated plasma CORT, indicating disruption of eCB-mediated constitutive inhibition of activity. CB1R blockade also potentiated stress-induced hormone levels and c-fos mRNA in several regions such as the bed nucleus of the stria terminalis (BST), lateral septum (LS), and basolateral amygdala (BLA) and the paraventricular nucleus of the hypothalamus (PVN). CB1R mRNA was detected in all central tissues investigated, and the adrenal cortex, but at very low levels in the anterior pituitary gland. Interestingly, CB1R mRNA was rapidly and bidirectionally regulated in response to stress and/or antagonist treatment in some regions. eCBs therefore modulate the HPA axis by regulating both constitutive and activity-dependent inhibition at multiple levels.

Infection prevention in personal services settings: Evidence, gaps and the way forward.

BACKGROUND: Personal services is a continuously evolving industry that encompasses a variety of aesthetic treatments and personal enhancement services. Personal services are an important public health concern because delivery of service may pose potential health risks for both clients and workers. To date, there is a lack of evidence on the specific infection risks involved with personal services and the magnitude of these risks. While guidance and regulation of personal services settings do exist, they appear in varying degrees and complexity across Canada. OBJECTIVES: To summarize relevant literature on the risk of infections related to personal services; conduct an environmental scan of current provincial and territorial guidance and regulations; identify key risk mitigation measures; and summarize gaps and challenges. METHODS: A working group of national experts in the field was established for consultation on key issues. A narrative literature review was conducted to summarize findings from relevant articles. Key questions and a literature search strategy were developed and articles were screened and critically appraised for eligibility. An environmental scan of key guidelines was also conducted to identify relevant legislation and guidance. Findings from both the narrative review and environmental scan were summarized to inform guidance and identify gaps. FINDINGS: The review of the literature identified factors associated with increased risk of infection including inadequate training of personal services workers and non-compliance with established infection prevention principles. The environmental scan demonstrated that some guidelines have been developed by provincial/territorial ministries of health utilizing basic, generally accepted infection prevention principles. The established body of evidence that informs infection prevention and control recommendations is valid for health care settings; however there are factors to consider in extracting and applying such guidance to personal services settings. Major gaps and challenges remain in supporting both the advancement of infection prevention guidance and the development of enhanced regulatory frameworks, applicable to personal services settings in Canada. CONCLUSION: This review involved a comprehensive examination of relevant literature and provides a summary of issues addressing the risk of infection in personal services settings. There is a paucity of high quality evidence to support guidance, and findings reveal the need for further investigation and enhanced awareness of public health risks associated with personal services. Nonetheless, these findings can inform future research and the development of infection prevention and control guidelines and recommendations for such settings.

Nephrotoxicity of iodixanol versus ioversol in patients with chronic kidney disease: the Visipaque Angiography/Interventions with Laboratory Outcomes in Renal Insufficiency (VALOR) Trial.

BACKGROUND: Iso-osmolar contrast medium iodixanol has been reported to be less nephrotoxic than selected low-osmolar contrast media (LOCM) in chronic kidney disease (CKD) patients with diabetes mellitus. This study compared the nephrotoxicity of iodixanol and the LOCM ioversol in CKD patients undergoing coronary angiography. METHODS: This is a prospective double-blind trial in 337 patients with stable CKD who were randomly assigned to receive the iso-osmolar contrast medium iodixanol or the LOCM ioversol. The co-primary end points were the mean peak percentage change (MPPC) in baseline serum creatinine and the incidence of contrast-induced nephropathy (rise of > 0.5 mg/dL in baseline serum creatinine within 72 hours postcontrast) for the 2 contrast media in the 72-hour period after contrast administration. Prespecified analyses included stratification on diabetic state and the use of N-acetylcysteine. RESULTS: In the 299 patients with complete post-contrast media creatinine data, the incidence of contrast-induced nephropathy was 21.8% in the iodixanol subjects and 23.8% in the ioversol subjects (P = .78). For all patients, the MPPC was 14.7% with iodixanol and 20.0% with ioversol (P = .06), whereas in the subset of diabetic patients, this value was significantly lower in the iodixanol (12.9%) compared with the ioversol subjects (22.4%, P = .01). CONCLUSIONS: Overall, the nephrotoxicity associated with iodixanol was not significantly different from that observed with ioversol in CKD patients undergoing coronary angiography, although in diabetic patients, MPPC was significantly lower in the iodixanol group.

No need for nanny.

The term "nanny state" is regularly used to attack health groups or governments, especially by interest groups bereft of arguments and journalists in search of a cliché. It has become a special favourite of tobacco companies and their supporters. In the present work we argue that the term should be retired in favour of genuine debate on substantive issues.

Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers.

We describe a model to study the effects of polymorphonuclear leukocyte (PMN) transmigration on the intestinal epithelial barrier. Human PMN were induced to transmigrate across high resistance monolayers of a cultured human intestinal epithelial cell line (T84 cells) by chemotactic gradients produced by formyl methionyl leucyl phenylalanine (FMLP). With maximal transmigration monolayer resistance decreased by 48 +/- 12.6% in 15 min and by 83 +/- 1.6% in 60 min. This response was dependent on the size of the FMLP gradient and the density of PMN transmigration. The decrease in resistance correlated with number of PMN migrating across monolayers, and was accompanied by increases in flux of paracellular tracers. Macromolecular tracer studies localized the leak sites to foci at which PMN impaled the epithelium. Removal of the chemotactic gradient led to restoration of baseline resistance within 18 h. PMN transmigration across intestinal epithelial monolayers occurs via intercellular occluding junctions and may be associated with a reversible increase in epithelial permeability.

Interferon-gamma directly affects barrier function of cultured intestinal epithelial monolayers.

Although epithelia, which often are in intimate contact with lymphoid cells, may bear receptors for various cytokines, it is unclear whether cytokines directly effect epithelial function. We examine the effects of the cytokine interferon (IFN) on barrier function of cultured monolayers of the T84 human intestinal epithelial cell line. Gamma IFN, in concentrations and exposures required to show its other biological effects, directly affects such monolayers. Monolayer resistance is substantially diminished by gamma IFN. Such effects were not due to cytotoxicity as judged morphologically and by LDH assays. Solute fluxes and dual Na+-mannitol flux analysis indicate that the resistance decrease is due to an effect of gamma IFN on tight junction permeability. The effects of gamma IFN on monolayer barrier function were not duplicated by the cytokines interleukin 1, interleukin 2, or tumor necrosis factor. We speculate that such products of activation of lymphoid cells might influence barrier function of intestinal, and perhaps other epithelia in disease states.