Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control.
Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ? 0.5 ?C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R.
An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.
Cites: Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R329-4019923364
Cites: Gerontology. 2010;56(2):220-3019602865
Cites: Am J Physiol Regul Integr Comp Physiol. 2011 Nov;301(5):R1440-5221865542
Cites: Transplantation. 2011 Dec 15;92(11):1215-2122082817
Cites: Am J Respir Crit Care Med. 2011 Sep 15;184(6):647-5521680948
The partial opiate-receptor agonist buprenorphine has been suggested for treatment of heroin dependence, but there are few long-term and placebo-controlled studies of its effectiveness. We aimed to assess the 1-year efficacy of buprenorphine in combination with intensive psychosocial therapy for treatment of heroin dependence.
40 individuals aged older than 20 years, who met DSM-IV criteria for opiate dependence for at least 1 year, but did not fulfil Swedish legal criteria for methadone maintenance treatment were randomly allocated either to daily buprenorphine (fixed dose 16 mg sublingually for 12 months; supervised daily administration for a least 6 months, possible take-home doses thereafter) or a tapered 6 day regimen of buprenorphine, thereafter followed by placebo. All patients participated in cognitive-behavioural group therapy to prevent relapse, received weekly individual counselling sessions, and submitted thrice weekly supervised urine samples for analysis to detect illicit drug use. Our primary endpoint was 1-year retention in treatment and analysis was by intention to treat.
1-year retention in treatment was 75% and 0% in the buprenorphine and placebo groups, respectively (p=0.0001; risk ratio 58.7 [95% CI 7.4-467.4]). Urine screens were about 75% negative for illicit opiates, central stimulants, cannabinoids, and benzodiazepines in the patients remaining in treatment.
The combination of buprenorphine and intensive psychosocial treatment is safe and highly efficacious, and should be added to the treatment options available for individuals who are dependent on heroin.
Comment In: Lancet. 2003 May 31;361(9372):1907; author reply 1907-812788596
Comment In: Lancet. 2003 Feb 22;361(9358):634-512606172
Comment In: Lancet. 2003 May 31;361(9372):1906-7; author reply 1907-812788595
An open-label randomized study was undertaken to compare a 2-dose regimen (Months 0 and 6) of hepatitis B surface antigen (HBsAg) vaccine formulated with a novel adjuvant (HBsAg/AS04) with a standard 3-dose regimen (Months 0, 1 and 6) of licensed recombinant HBsAg vaccine in terms of immunogenicity and reactogenicity when administered to healthy subjects aged between 15 and 40 y. At 1 and 6 months after the full vaccination course there was a 100% seroprotection rate (anti-HBs > or = 10 mIU/ml) with the HBsAg/AS04 vaccine, compared with a 99% response rate with the licensed vaccine. The corresponding geometric mean titres were significantly higher for the novel vaccine compared to the standard vaccine: 15,468 and 2,745 mIU/ml at Months 7 and 12 vs. 6,274 and 1,883 mIU/ml, respectively. There was a higher prevalence of local symptoms with the adjuvant vaccine (90% of doses) than with the standard vaccine (48% of doses). However, these symptoms (pain, swelling and redness) were predominantly of mild-to-moderate intensity and resolved rapidly without treatment. A 2-dose regimen of the new HBsAg/AS04 adjuvant vaccine therefore compared favourably to the standard regimen in healthy young adults. It is anticipated that the simplified vaccination schedule may improve compliance and reduce costs.
OBJECTIVES: HIV/AIDS surveillance methods are under revision as the diversity of HIV epidemics is becoming more apparent. The so called "2nd generation surveillance (SGS) systems" aim to enhance surveillance by broadening the range of indicators to prevalence, behaviors and correlates, for a better understanding and a more complete and timely awareness of evolving epidemics. METHODS: Concepts of HIV SGS are reviewed with a special focus on injecting drug users, a major at-risk and hard to reach group in Europe, a region with mainly low or concentrated epidemics. RESULTS: The scope of HIV/AIDS surveillance needs to be broadened following principles of SGS. Specifically for IDUs we propose including hepatitis C data as indicator for injecting risk in routine systems like those monitoring sexually transmitted infections and information on knowledge and attitudes as potential major determinants of risk behavior. CONCLUSIONS: The suggested approach should lead to more complete and timely information for public health interventions, however there is a clear need for comparative validation studies to assess the validity, reliability and cost-effectiveness of traditional and enhanced HIV/AIDS surveillance systems.
PURPOSE: To evaluate the clinical performance of Helioseal-F, a fluoride-containing fissure sealant, in school children at caries risk. MATERIALS AND METHODS: A caries risk assessment based on past caries experience, saliva microbial tests, buffer capacity and frequency of sugar intake was carried out in 204 healthy children, 6-7 years of age. Children exhibiting one or more risk factors were considered at caries risk (n = 121) and their permanent molars were sealed with a fluoride-containing fissure sealant, thus forming a fissure sealant group (FSG). The remaining 83 children with low caries risk received no fissure sealants and constituted a reference group (RG). Both groups were followed for 2 years. From 15 children of both groups, unstimulated whole saliva was collected 1 month after sealant placement in order to determine fluoride levels. In another 20 children, a split-mouth study design was utilized to compare the colonization of mutans streptococci adjacent to and on F-containing sealants and conventional controls. The sealants were placed by dental hygienists according to the manufacturers' instructions. RESULTS: A total of 431 fissure sealants were placed at baseline. Complete retention was found in 76.6% during the study period while 22.0% were partially lost. Six sealants (1.4%) were completely lost. The enamel caries incidence was 45% lower (P
To measure the effectiveness of fluoride varnish (FV) (Duraflor), 5% sodium fluoride, Pharmascience Inc., Montréal, QC, Canada) and caregiver counseling in preventing early childhood caries (ECC) in Aboriginal children in a 2-year community-randomized controlled trial.
Twenty First Nations communities in the Sioux Lookout Zone (SLZ), Northwest Ontario, Canada were randomized to two study groups. All caregivers received oral health counseling, while children in one group received FV twice per year and the controls received no varnish. A total of 1275, 6 months to 5-year-old children from the SLZ communities were enrolled. In addition, a convenience sample of 150 primarily non-Aboriginal children of the same age were recruited from the neighboring community of Thunder Bay and used as comparisons. Longitudinal examinations for the dmft/s indices were conducted by calibrated hygienists in 2003, 2004 and 2005.
Aboriginal children living in the SLZ or in Thunder Bay had significantly higher caries prevalence and severity than non-Aboriginal children in Thunder Bay. FV treatment conferred an 18% reduction in the 2-year mean 'net' dmfs increment for Aboriginal children and a 25% reduction for all children, using cluster analysis to adjust for the intra-cluster correlation among children in the same community. Adjusted odds ratio for caries incidence was 1.96 times higher in the controls than in the FV group (95% CI = 1.08-3.56; P = 0.027). For those caries-free at baseline, the number (of children) needed to treat (NNT) equaled 7.4.
Findings support the use of FV at least twice per year, in conjunction with caregiver counseling, to prevent ECC, reduce caries increment and oral health inequalities between young Aboriginal and non-Aboriginal children.
OBJECTIVES: The aim of this study was to determine if there were any long-lasting elevated anxiety levels in women attending colposcopy after an abnormal cervical smear. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynaecology, MalmÃ??Ã?Â¶ University Hospital, Sweden. POPULATION: One hundred consecutive women were invited to participate when referred for colposcopy. METHODS: Women in the study group completed the State-Trait Anxiety Inventory, the Montgomery-Asberg Depression Rating Scale-self-rate (MADRS-S) and had a psychosocial interview prior to colposcopy at their two follow-up visits. MAIN OUTCOME MEASURES: State anxiety levels and depression scores at first visit, 6 months and 2 years. RESULTS: At follow up, levels of state anxiety and the depression scores of the women studied had decreased and were comparable to those of Swedish normative data. Two variables from the MADRS-S, 'ability to focus on different activities' and 'emotional involvement with others and in activities' were the most prominent for women with moderate to severe depression. At the 2-year visit, 30% of the women still had a fear of cancer. CONCLUSIONS: Referral for colposcopy after an abnormal cervical smear does not seem to result in long-lasting anxiety and depression. However, a subgroup of women, with the initially highest depression scores, still had at 2-year state anxiety levels and depression scores significantly higher than normal. Almost one-third of the women still had a fear of cancer in spite of lower 2-year state anxiety levels.
A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.
Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population.
In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989.
Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control).
Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population.
Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.
The results of screening more than 23,000 serum samples from persons belonging to risk groups, as well as those not belonging to such groups, in Moscow, Vilnius and Klaipeda are presented. Screening was carried out with the use of an assay system manufactured by the Scientific and Industrial Amalgamation "Antigen" (USSR). In this screening 3 HIV carriers were detected; of these, 2 were foreign students from two African countries.
Andreeva Bay in northwest Russia hosts one of the former coastal technical bases of the Northern Fleet. Currently, this base is designated as the Andreeva Bay branch of Northwest Center for Radioactive Waste Management (SevRAO) and is a site of temporary storage (STS) for spent nuclear fuel (SNF) and other radiological waste generated during the operation and decommissioning of nuclear submarines and ships. According to an integrated expert evaluation, this site is the most dangerous nuclear facility in northwest Russia. Environmental rehabilitation of the site is currently in progress and is supported by strong international collaboration. This paper describes how the optimization principle (ALARA) has been adopted during the planning of remediation work at the Andreeva Bay STS and how Russian-Norwegian collaboration greatly contributed to ensuring the development and maintenance of a high level safety culture during this process. More specifically, this paper describes how integration of a system, specifically designed for improving the radiological safety of workers during the remediation work at Andreeva Bay, was developed in Russia. It also outlines the 3D radiological simulation and virtual reality based systems developed in Norway that have greatly facilitated effective implementation of the ALARA principle, through supporting radiological characterisation, work planning and optimization, decision making, communication between teams and with the authorities and training of field operators.