The impact of cultural identity, parental communication, and peer influence on substance use among Indigenous youth in Canada.

Heavy drinking and smoking have been found to be among the leading causes of morbidity and mortality within Indigenous youth in North America. The focus of this study was to examine the relative roles of cultural identity, parent-child communication about the harms of substance use (SU), and perception about peers' opinions on heavy drinking and cigarette smoking among Indigenous youth. Strong Indigenous cultural identity, parent-child communication about SU, and affiliation with peers who do not use and/or who disapprove of substance use were all expected to reduce risk for heavy drinking and smoking. Substance use beliefs were hypothesized to mediate these effects. Youth (N = 117; Mage = 14.07; grades 6-11) from two Indigenous communities in Quebec completed self-reports. Consistent with the hypotheses, strong cultural identity predicted increased negative beliefs about substance use, which predicted reduced drinking and smoking. Similarly, affiliating with peers who did not use alcohol predicted decreased positive beliefs about alcohol use, which predicted reduced drinking. Affiliating with peers who did not smoke cigarettes predicted reduced cigarette smoking. Parental influences were not supported in this model. Intervention strategies may benefit from targeting cultural identity, peer groups, and substance use beliefs among Indigenous youth.

Medical Rapid Response in Psychiatry: Reasons for Activation and Immediate Outcome.

Rapid response teams are used to improve the recognition of acute deteriorations in medical and surgical settings. They are activated by abnormal physiological parameters, symptoms or clinical concern, and are believed to decrease hospital mortality rates. We evaluated the reasons for activation and the outcome of rapid response interventions in a 222-bed psychiatric hospital in New York City using data obtained at the time of all activations from January through November, 2012. The primary outcome was the admission rate to a medical or surgical unit for each of the main reasons for activation. The 169 activations were initiated by nursing staff (78.7 %) and psychiatrists (13 %) for acute changes in condition (64.5 %), abnormal physiological parameters (27.2 %) and non-specified concern (8.3 %). The most common reasons for activation were chest pain (14.2 %), fluctuating level of consciousness (9.5 %), hypertension (9.5 %), syncope or fall (8.9 %), hypotension (8.3 %), dyspnea (7.7 %) and seizures (5.9 %). The rapid response team transferred 127 (75.2 %) patients to the Emergency Department and 46 (27.2 %) were admitted to a medical or surgical unit. The admission rates were statistically similar for acute changes in condition, abnormal physiological parameters, and clinicians' concern. In conclusion, a majority of rapid response activations in a self-standing psychiatric hospital were initiated by nursing staff for changes in condition, rather than for policy-specified abnormal physiological parameters. The findings suggest that a rapid response system may empower psychiatric nurses to use their clinical skills to identify patients requiring urgent transfer to a general hospital.

Sensitivity to seizure-like activity in Drosophila following acute hypoxia and hypercapnia.

Human seizure disorders represent a heterogeneous collection of neuropathies, many of which are poorly understood. To investigate the etiology of seizure disorders, we have used a group of Drosophila mutants known as the bang-sensitive (BS) paralytics. The BS mutants exhibit seizure-like activity (SLA) following a wide variety of insults including mechanical shock, electrical shock, high frequency light and cold temperatures. In this study, we show that two novel insults, hypoxia and hypercapnia (elevated CO(2) levels) are potent triggers of SLA in a number of the BS mutants. We also show that both of these insults, hypoxia and hypercapnia, can trigger SLA in wild-type flies as well. However, we find that the BS mutants are more susceptible than wild-type flies to these insults as they exhibit more SLA following these insults and, in the case of hypercapnia, they exhibit SLA at a lower threshold. In addition, we demonstrate that the BS mutants are more susceptible to the anesthetizing effects of CO(2) as compared to wild-type flies. The increased sensitivity to both hypoxia and hypercapnia in these BS mutants suggests possible physiological defects that may underlie seizure susceptibility.

Giant cell tubulitis with immune complex deposits in a patient with lupus nephritis.

We report a case of acute tubulointerstitial nephritis with giant cell tubulitis and tubular basement membrane immune complex deposits in a patient with membranous lupus nephritis. The patient, who had no prior evidence of lupus nephritis, developed acute kidney failure and mild proteinuria after cardiac valve replacement surgery. Giant cell tubulitis with tubular basement membrane immune complex deposits has been described in 4 patients after cardiac surgery, 3 of whom received cefuroxime, suggesting the possibility of a drug hypersensitivity reaction. The present case suggests there may also be a pathogenetic role for autoimmunity in this condition.

Vaccine-induced early control of hepatitis C virus infection in chimpanzees fails to impact on hepatic PD-1 and chronicity.

UNLABELLED: Broad T cell and B cell responses to multiple HCV antigens are observed early in individuals who control or clear HCV infection. The prevailing hypothesis has been that similar immune responses induced by prophylactic immunization would reduce acute virus replication and protect exposed individuals from chronic infection. Here, we demonstrate that immunization of naïve chimpanzees with a multicomponent HCV vaccine induced robust HCV-specific immune responses, and that all vaccinees exposed to heterologous chimpanzee-adapted HCV 1b J4 significantly reduced viral RNA in serum by 84%, and in liver by 99% as compared to controls (P=0.024 and 0.028, respectively). However, despite control of HCV in plasma and liver in the acute period, in the chronic phase, 3 of 4 vaccinated animals developed persistent infection. Analysis of expression levels of proinflammatory cytokines in serial hepatic biopsies failed to reveal an association with vaccine outcome. However, expression of IDO, CTLA-4 [corrected] and PD-1 levels in liver correlated with clearance or chronicity. CONCLUSION: Despite early control of virus load, a virus-associated tolerogenic-like state can develop in certain individuals independent of vaccination history.

IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy.

Two pathological patterns of acute poststaphylococcal glomerulonephritis are well defined and include (1) an acute proliferative and exudative glomerulonephritis closely resembling classical acute poststreptococcal glomerulonephritis in patients with Staphylococcus aureus infection and (2) a membranoproliferative glomerulonephritis in patients with Staphylococcus epidermidis infection secondary to ventriculovascular shunts. In this study, we report a novel immunopathologic phenotype of immunoglobulin (Ig) A-dominant acute poststaphylococcal glomerulonephritis occurring in patients with underlying diabetic nephropathy. Five patients with type 2 diabetes presented with acute renal failure occurring after culture-positive staphylococcal infection. Renal biopsy disclosed an atypical pattern of acute endocapillary proliferative and exudative glomerulonephritis with intense deposits of IgA as the sole or dominant immunoglobulin, mimicking IgA nephropathy. The deposits were predominantly mesangial in distribution with few subepithelial humps. All five cases occurred superimposed on well-established diabetic nephropathy. Outcome was poor with irreversible renal failure in four of five (80%) cases. The possible pathophysiological basis of this atypical form of acute poststaphylococcal glomerulonephritis in diabetic patients is explored. Proper recognition of this entity is needed to avoid an erroneous diagnosis of IgA nephropathy, with corresponding therapeutic and prognostic implications.

A method for the absolute quantification of cDNA using real-time PCR.

Real-time PCR is an extremely powerful technique, however, often its results are open to interpretation since there is no convention for data presentation. This anomaly has arisen because many applications rely on non-standard calibration genes, which themselves often change in value during experimental manipulation. We present a novel method for absolute quantification of cDNA species using a combination of extremely accurate double-stranded DNA quantification and a plasmid reference curve. PicoGreen and reference standards are used to measure the amount of cDNA present in a sample using fluorescence. Real-time PCR products are cloned into plasmids and then used to calibrate unknown samples. This cloning is achieved using the same primers necessary for real-time PCR and thus does not involve a second design stage. Results are expressed as copy number per microgram of oligo-dT primed cDNA and consequently may be compared between both inter and intra-experimentally. We show results from a sample human system in which absolute levels of interferon-gamma, TNF-alpha, interleukin-2 and interleukin-10 are measured. We further compare the copy numbers of these genes with levels of released protein and find remarkable correlation. Although our interest has been cytokine quantification, we believe that this technique is widely applicable to the majority of real-time PCR applications.

Cancer immunotherapy: an embarrassment of riches?

There is clear evidence that certain forms of immunotherapy can be successful against certain cancers. However, it would appear that cancerous cells of various origin are exceptionally adept at subverting the immune response. Consequently, it is probable that the most efficacious therapy will be one in which multiple responses of the immune system are activated. There is currently an embarrassment of riches with regard to multiple vaccine strategies in the clinic, although no single method seems to hold the solution. Here, we draw together several of the humoral- and cellular-activating strategies currently under clinical investigation.