One leg standing time predicts fracture risk in older women independent of clinical risk factors and BMD.

In women of ages 75-80 years, a low one leg standing time (OLST) was associated with an increased risk of incident fractures, independently of bone mineral density and clinical risk factors. OLST contributed substantially to fracture probability, indicating that the test should be considered when evaluating fracture risk in older women. INTRODUCTION: Physical function and risk of falls are important risk factors for fracture. A few previous studies have suggested that a one leg standing time (OLST) less than 10 s predicts fracture risk, but the impact of OLST, in addition to known clinical risk factors, for fracture probability is unknown. The aim of this study was to determine the independent contribution of OLST to fracture probability in older women. METHODS: The Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures (SUPERB) is a prospective population-based study of 3028 women 75-80 years old, recruited from the greater Gothenburg area in Sweden. At baseline, information on risk factors was collected using questionnaires, bone mineral density was measured with dual-energy X-ray absorptiometry (DXA), and OLST was performed. RESULTS: During a median follow-up of 3.6 years (IQR 1.5 years), X-ray-verified incident fractures were identified using health records. OLST was available in 2405 women. OLST less than 10 s was associated with an increased risk for incident hip fracture (Hazard Ratio (HR) 3.02, 95% Confidence Interval (CI) [1.49-6.10]), major osteoporotic fracture (HR 95% CI 1.76 [1.34-1.46]), and nonvertebral fracture (HR 95% CI 1.61 [1.26-2.05]) in Cox regression analyses adjusted for age, height, and weight. Depending on BMD, the 4-year fracture probability increased by a factor of 1.3 to 1.5 in a 75-year-old woman with a low OLST (<10 s). CONCLUSION: A low OLST has a substantial impact on fracture probability and should be considered when evaluating fracture risk in older women.

Impact of an education program to facilitate nurses' discussions of existential issues in neurological care.

OBJECTIVES: Discussing existential issues is integral to caring for people with acute, progressive, or life-limiting neurological illness, but there is a lack of research examining how nurses approach existential issues with this patient group and their family members. The purpose was to examine the experiential impact of an educational program for nurses designed to facilitate discussions of existential issues with patients and family members in neurological wards. METHOD: Nurses in inpatient and outpatient care at a neurological clinic in Sweden were invited to participate in an education program about discussing existential issues with patients and their family members as related to neurological conditions. The evaluation of the program and of the nurses' view of discussing existential issues was conducted through focus groups before and after participation. The data were analyzed by qualitative content analysis. RESULTS: The program gave nurses a deeper understanding of existential issues and how to manage these conversations with patients and their family members. Both internal and external barriers remained after education, with nurses experiencing insecurity and fear, and a sense of being inhibited by the environment. However, they were more aware of the barriers after the education, and it was easier to find strategies to manage the conversations. They demonstrated support for each other in the team both before and after participating in the program. SIGNIFICANCE OF RESULTS: The educational program gave nurses strategies for discussing existential issues with patients and family members. The knowledge that internal and external barriers impede communication should compel organizations to work on making conditions more conducive, for example, by supporting nurses to learn strategies to more easily manage conversations about existential issues and by reviewing the physical environment and the context in which they are conducted.

The timed up and go test predicts fracture risk in older women independently of clinical risk factors and bone mineral density.

The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. In older women, TUG time predicts the risk of major osteoporotic fracture and hip fracture independently of clinical risk factors and bone mineral density, and has a substantial impact on fracture probabilities. INTRODUCTION: The timed up and go (TUG) test measures physical performance and predicts falls in the elderly. A slow TUG has been associated with an increased fracture risk, but it is unclear whether the association is independent of clinical risk factors and bone mineral density (BMD). The aim of this study was to investigate if TUG time was associated with fracture risk independently of clinical risk factors and BMD and to determine its impact on fracture probabilities in older women. METHODS: A standardized questionnaire was used to assess information regarding clinical risk factors in the large population-based SUPERB study of 3028 older women (75-80 years). At baseline, the TUG test was performed and BMD measured with DXA. The association between TUG time and the risk of hip fracture and major osteoporotic fracture (MOF) was examined using an extension of Poisson regression. RESULTS: Fracture incidence increased steeply with increasing TUG time up to 12 s and subsequently started to level off. A slow TUG time was therefore defined as TUG > 12 s, a cutoff level then used in Cox models to study the association between slow TUG and fracture risk. A slow TUG time was associated with an increased risk of fracture (MOF 2.39 [1.80-3.18] and hip fracture 2.96 [1.62-5.40]). These associations were slightly attenuated but remained significant after adjustment for clinical risk factors and femoral neck BMD. Depending on BMD, the 4-year fracture probability of MOF increased by a factor of 1.5-1.9 in a 75-year-old woman with slow TUG (> 12 s). CONCLUSION: The TUG time predicts the risk of MOF and hip fracture independently of clinical risk factors and BMD and has a substantial impact on fracture probabilities, indicating that inclusion of the TUG test in patient evaluation should be considered in order to improve fracture prediction in older women.

Pain intensity and pressure pain thresholds after a light dynamic physical load in patients with chronic neck-shoulder pain.

BACKGROUND: To investigate the development of pain intensity and pressure pain thresholds during and 24 h after a light dynamic physical load among patients with chronic neck-shoulder pain. METHODS: Twenty-six patients with chronic neck-shoulder pain and 12 healthy controls were included. The participants arm-cycled on an ergometer. Effort was rated with the Borg Rating of Perceived Exertion scale (RPE), and pain intensity with an numeric rating scale (NRS). Pressure pain thresholds were measured by an algometer. Participants started a pain diary 1 week before the physical exercise and continued until 1 week after. Pain intensity was assessed before, during and the following two evenings after arm-cycling. Pressure pain thresholds were assessed before, 15 min after, 105 min after and 24 h after. RESULTS: The chronic pain group showed increased pain intensity during, and the following two evenings after the arm cycling, and decreased pain thresholds immediately after the arm cycling involving painful regions. In the patient group there were no impact on pain thresholds in the neck the following day. CONCLUSIONS: Patients with chronic neck-shoulder pain reported increased pain intensity during and in the evenings after a light dynamic load involving painful regions. In addition, they showed decreased pain thresholds close to the exercise, indicating mechanical hyperalgesia.

Circulating cartilage oligomeric matrix protein in juvenile idiopathic arthritis.

OBJECTIVES: Raised serum cartilage oligomeric matrix protein (sCOMP) has been reported to predict erosive disease in early rheumatoid arthritis (RA). In juvenile idiopathic arthritis (JIA), subnormal sCOMP levels have been associated with ongoing inflammation and growth retardation. In this study we aimed to assess sCOMP, C-reactive protein (CRP), and insulin-like growth factor (IGF)-1 in children/adolescents with JIA and in referents. METHOD: We enrolled 52 JIA patients at planned outpatient visits and 54 inpatients with ongoing infection ('infection referents'). A total of 120 referents testing negative for immunoglobulin (Ig)E-mediated allergy ('IgE referents') served as controls. All serum samples were analysed for COMP, IGF-1, and CRP. RESULTS: The average sCOMP level was highest among the IgE referents and lowest among the infection referents. In the JIA patients, the level of sCOMP was not associated with the level of CRP or with clinical signs of disease activity. CONCLUSIONS: The results of this study do not support routine clinical analysis of sCOMP levels in patients with JIA.

A prospective study of quality of life in amyotrophic lateral sclerosis patients.

OBJECTS: The aim of this prospective and longitudinal study was to describe individual quality of life in patients with amyotrophic lateral sclerosis (ALS) and its correlations with physical function and emotional well-being from diagnosis and over time. MATERIALS AND METHODS: Thirty-six patients were included in the study. Individual quality of life was measured with the Schedule of Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW), illness severity was assessed using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS FRS-R), and emotional distress was measured using the Hospital Anxiety and Depression Scale (HADS). Data were collected from diagnosis and thereafter, every six months for a period of two years. Twelve patients completed the 24-month follow-up. RESULTS: Family, friends and own physical health were important for overall quality of life, from diagnosis and during the disease progression. Most patients had good quality of life, which remained stable, despite changed physical functions. Several patients scored above the cut-off score for doubtful and clinical anxiety and depression early on after diagnosis, and there was a significant decrease in anxiety over time. Soon after diagnosis, there was a correlation between depression and quality of life. CONCLUSION: The family, social relations and own physical health are important for overall quality of life in patients with ALS. Thus, supporting the family and facilitating so that patients can continue to stay in contact with friends are important aspects during the disease. Conducting an early screening for depression can be important for preventing decreased quality of life.

Different DHEA-S Levels and Response Patterns in Individuals with Chronic Neck Pain, Compared with a Pain Free Group-a Pilot Study.

Objective: To test, in this pilot study, whether DHEA-S (Dehydroepiandrosterone, sulfated form) plasma levels are lower among persons with chronic neck pain, compared to control persons, and to investigate the DHEA-S response after a physical exercise. Subjects: Included were 12 persons with chronic neck pain and eight controls without present pain, all 18 and 65 years of age. Exclusion criteria for both groups were articular diseases or tendinosis, fibromyalgia, systemic inflammatory and neuromuscular diseases, pain conditions due to trauma, or severe psychiatric diseases. Design and methods: The participants arm-cycled on an ergometer for 30 minutes. Blood samples were taken before, 60 minutes, and 150 minutes after this standardized physical exercise. Results: The estimated plasma DHEA-S levels at baseline were 2.0 µmol/L (95% confidence interval [CI] 1.00; 4.01) in the pain group and 4.1 µmol/L (95% CI2.0; 8.6) in the control group, adjusted for sex, age, body mass index (BMI), and Shirom-Melamed Burnout Questionnaire (SMBQ), with a ratio of 0.48 ( P = 0.094). Conclusions: In this pilot study, the plasma DHEA-S levels appeared to be lower among the persons with chronic neck pain, compared with the control group. It was indicated that DHEA-S decreased during the physical exercise in the control group, and either increased or was unaffected in the chronic pain group.

The safety and tolerability of oral AZD5069, a selective CXCR2 antagonist, in patients with moderate-to-severe COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by neutrophil-dominated airway mucosal inflammation and elevated neutrophil counts in sputum and lung tissue. CXC chemokine receptor 2 (CXCR2) is predominantly expressed on neutrophils and mediates the migration of neutrophils to inflammatory sites. AZD5069 is a small molecule CXCR2 antagonist with the potential to inhibit neutrophil migration into the airways in patients with COPD. METHODS: This 4-week, randomized, double-blind, placebo-controlled, parallel-group, multi-center, Phase IIa study evaluated the safety and tolerability of AZD5069 in patients with moderate-to-severe COPD (ClinicalTrials.gov identifier: NCT01233232). The pharmacokinetics and effect of AZD5069 on blood neutrophil counts were also assessed. Patients completed daily diary cards and attended weekly clinic visits for safety assessments. RESULTS: 87 patients (mean FEV1 56% pred; mean age 64 years; 69% male) were randomized to receive placebo (n = 29), AZD5069 50 mg bid (n = 30) or AZD5069 80 mg bid (n = 28) for 4 weeks. AZD5069 was well tolerated with adverse events (AEs) reported in 9 (31%), 10 (33%) and 6 (21%) patients in the placebo, AZD5069 50 mg and AZD5069 80 mg groups, respectively. AEs were generally mild or moderate in severity. The incidence of infections, the most commonly reported AE, was similar across the three groups (17%, 17% and 11% of patients in the placebo, AZD5069 50 and 80 mg groups, respectively). Blood neutrophil counts decreased on average from baseline by 14-40% and 13-36% in the AZD5069 50 mg and 80 mg groups, respectively, and 4 patients discontinued from the study due to decreased neutrophil count, 3 in the AZD5069 50 mg group and 1 in the 80 mg group. The systemic exposure (AUC and Cmax) of AZD5069 increased less than in proportion to the dose and there was a large overlap in the individual exposures between the two dose levels. CONCLUSIONS: AZD5069 was well tolerated overall in those patients who completed study treatment, with no increase in infection rates in either dosage group compared with placebo. Further studies with AZD5069 appear to be warranted.

Comparative metabolomics of muscle interstitium fluid in human trapezius myalgia: an in vivo microdialysis study.

PURPOSE: The mechanisms behind trapezius myalgia are unclear. Many hypotheses have been presented suggesting an altered metabolism in the muscle. Here, muscle microdialysate from healthy and myalgic muscle is analysed using metabolomics. Metabolomics analyse a vast number of metabolites, enabling a comprehensive explorative screening of the cellular processes in the muscle. METHODS: Microdialysate samples were obtained from the shoulder muscle of healthy and myalgic subjects that performed a work and stress test. Samples from the baseline period and from the recovery period were analysed using gas chromatography­mass spectrometry (GC­MS) together with multivariate analysis to detect differences in extracellular content of metabolites between groups. Systematic differences in metabolites between groups were identified using multivariate analysis and orthogonal partial least square discriminate analysis (OPLS-DA). A complementary Mann­Whitney U test of group difference in individual metabolites was also performed. RESULTS: A large number of metabolites were detected and identified in this screening study. At baseline, no systematic differences between groups were observed according to the OPLS-DA. However, two metabolites, l-leucine and pyroglutamic acid, were significantly more abundant in the myalgic muscle compared to the healthy muscle. In the recovery period, systematic difference in metabolites between the groups was observed according to the OPLS-DA. The groups differed in amino acids, fatty acids and carbohydrates. Myristic acid and putrescine were significantly more abundant and beta-d-glucopyranose was significantly less abundant in the myalgic muscle. CONCLUSION: This study provides important information regarding the metabolite content, thereby presenting new clues regarding the pathophysiology of the myalgic muscle.

Movement-evoked breakthrough cancer pain despite intrathecal analgesia: a prospective series.

BACKGROUND: Intrathecal analgesia (ITA) is a valuable treatment option for intractable cancer-related pain. However, the issue of movement-evoked breakthrough pain (BTP) has not been specifically investigated in the ITA setting. The aim of the study was to evaluate the effect of ITA on spontaneous resting pain intensity (SRPI), doses of non-ITA opioids, and specifically on movement-evoked pain intensity (MEPI). METHODS: We prospectively studied 28 consecutive patients who graded SRPI and MEPI on a 0-10 numerical rating scale (NRS) at the time of ITA procedure, after 1 week, and after 1 month. Mild pain was defined as NRS ≤ 3 and severe pain as NRS ≥ 7. Concomitant doses of opioids were registered. RESULTS: After 1 week, no patient had severe SRPI compared with 31% before ITA, and the proportion of patients with mild SRPI had increased from 27% to 76%. Meanwhile, the median daily dose of non-ITA opioids decreased from 575 to 120 mg of oral morphine equivalents. The effect on SRPI and on doses of non-ITA opioids remained essentially unchanged during the study month, but the proportion of patients having severe MEPI did not change significantly: 44% still had severe MEPI after 1 week and 40% after 1 month. CONCLUSION: Movement-evoked BTP was a major clinical problem throughout the study month despite otherwise successful ITA. Improving the quality of life of patients with intractable cancer-related pain should include developing strategies to better deal with movement-evoked BTP.

Effects of resistance training on endurance capacity and muscle fiber composition in young top-level cyclists.

Equivocal findings exist on the effect of concurrent strength (S) and endurance (E) training on endurance performance and muscle morphology. Further, the influence of concurrent SE training on muscle fiber-type composition, vascularization and endurance capacity remains unknown in top-level endurance athletes. The present study examined the effect of 16 weeks of concurrent SE training on maximal muscle strength (MVC), contractile rate of force development (RFD), muscle fiber morphology and composition, capillarization, aerobic power (VO2max), cycling economy (CE) and long/short-term endurance capacity in young elite competitive cyclists (n=14). MVC and RFD increased 12-20% with SE (P<0.01) but not E. VO2max remained unchanged. CE improved in E to reach values seen in SE. Short-term (5-min) endurance performance increased (3-4%) after SE and E (P<0.05), whereas 45-min endurance capacity increased (8%) with SE only (P<0.05). Type IIA fiber proportions increased and type IIX proportions decreased after SE training (P<0.05) with no change in E. Muscle fiber area and capillarization remained unchanged. In conclusion, concurrent strength/endurance training in young elite competitive cyclists led to an improved 45-min time-trial endurance capacity that was accompanied by an increased proportion of type IIA muscle fibers and gains in MVC and RFD, while capillarization remained unaffected.

Health effects of a subway environment in healthy volunteers.

Environmental particle exposure, often estimated as the particulate mass of particles with a diameter <10 microm, <2.5 microm or <1 microm (PM(10), PM(2.5) or PM(1)), is known to have a negative impact on the health of the population. Little is known about how the size and origin of particles influence the effects. We have previously shown that exposure to a road tunnel environment causes a cellular inflammatory response in the airways of healthy individuals. In the present study, our aim was to investigate potential airway health effects from exposure to a subway environment. 20 healthy volunteers were exposed to a subway and a control environment for 2 h, followed by measurements of lung function and the inflammatory response in the lower airways (bronchoscopy) and in the peripheral blood. No cellular response was found in the airways after exposure to the subway environment. In the blood, we found a statistically significant increase in fibrinogen and regulatory T-cells expressing CD4/CD25/FOXP3. Subway and road tunnel environments have similar levels of PM(10) and PM(2.5), whilst the concentrations of ultrafine particles, nitrogen monoxide and dioxide are lower in the subway. Although no cellular response was detected, the findings indicate a biological response to the subway environment. Our studies show that using gravimetric estimates of ambient particulate air pollution alone may have clear limitations in health-risk assessment.

Prevalence of asthma-like symptoms, asthma and its treatment in elite athletes.

The objective was to determine the prevalence of asthma-like symptoms and asthma and the use of asthma medication in Danish elite athletes. A cross-sectional questionnaire survey of Danish elite athletes was conducted in 2006. All elite athletes (N=418) financially supported by the national organization of elite athletes comprised the study group; 329 (79%) completed the questionnaire concerning their sport, asthma-like symptoms, asthma and use of asthma medication. Asthma-like symptoms at rest were reported by 41% of respondents; 55% reported asthma-like symptoms at rest or at exercise. Physician-diagnosed asthma was present in 16% and 14% had current asthma. Asthma medication was taken by 7% of the athletes, of whom 79% used inhaled corticosteroids and 21% used inhaled beta(2)-agonists only. Athletes participating in endurance sports had higher prevalences of current asthma (24%) and use of asthma medication (15%) than all other athletes (P<0.01). Athletes participating in endurance sports have a higher prevalence of asthma and use of asthma medication. The frequency of asthma medication is lower than the prevalence of current asthma indicating that there is no overuse of asthma medication among Danish elite athletes.

Exposure to Particles and Nitrogen Dioxide Among Workers in the Stockholm Underground Train System.

OBJECTIVES: Exposure to fine particles in urban air has been associated with a number of negative health effects. High levels of fine particles have been detected at underground stations in big cities. We investigated the exposure conditions in four occupational groups in the Stockholm underground train system to identify high-exposed groups and study variations in exposure. METHODS: PM1 and PM2.5 were measured during three full work shifts on 44 underground workers. Fluctuations in exposure were monitored by a real-time particle monitoring instrument, pDR, DataRAM. Qualitative analysis of particle content was performed using inductively coupled plasma mass spectrometry. Nitrogen dioxide was measured using passive monitors. RESULTS: For all underground workers, the geometric mean (GM) of PM1 was 18 µg/m3 and of PM2.5 was 37 µg/m3. The particle exposure was highest for cleaners/platform workers, and the GM of PM1 was 31.6 µg/m3 [geometric standard deviation (GSD), 1.6] and of PM2.5 was 76.5 µg/m3 (GSD, 1.3); the particle exposure was lowest for ticket sellers, and the GM of PM1  was 4.9 µg/m3 (GSD, 2.1) and of PM2.5 was 9.3 µg/m3 (GSD, 1.5). The PM1 and PM2.5 levels were five times higher in the underground system than at the street level, and the particles in the underground had high iron content. The train driver's nitrogen dioxide exposure level was 64.1 µg/m3 (GSD, 1.5). CONCLUSIONS: Cleaners and other platform workers were statistically significantly more exposed to particles than train drivers or ticket sellers. Particle concentrations (PM2.5) in the Stockholm underground system were within the same range as in the New York underground system but were much lower than in several older underground systems around the world.

Association of insomnia severity with well-being, quality of life and health care costs: A cross-sectional study in older adults with chronic pain (PainS65+).

BACKGROUND: Insomnia is one of the most common complaints in chronic pain. This study aimed to evaluate the association of insomnia with well-being, quality of life and health care costs. METHODS: The sample included 2790 older individuals (median age = 76; interquartile range [IQR] = 70-82) with chronic pain. The participants completed a postal survey assessing basic demographic data, pain intensity and frequency, height, weight, comorbidities, general well-being, quality of life and the insomnia severity index (ISI). Data on health care costs were calculated as costs per year (€ prices) and measured in terms of outpatient and inpatient care, pain drugs, total drugs and total health care costs. RESULTS: The overall fraction of clinical insomnia was 24.6% (moderate clinical insomnia: 21.9% [95% CI: 18.8-23.3]; severe clinical insomnia: 2.7% [95% CI: 1.6-3.2]). Persons who reported clinical insomnia were more likely to experience pain more frequently with higher pain intensity compared to those reported no clinically significant insomnia. Mean total health care costs were € 8469 (95% CI: €4029-€14,271) for persons with severe insomnia compared with € 4345 (95% CI: €4033-€4694) for persons with no clinically significant insomnia. An association between severe insomnia, well-being, quality of life, outpatient care, total drugs costs and total health care costs remained after controlling for age, sex, pain intensity, frequency, body mass index and comorbidities using linear regression models. CONCLUSIONS: Our results determine an independent association of insomnia with low health-related quality of life and increased health care costs in older adults with chronic pain. SIGNIFICANCE: The concurrence and the severity of insomnia among older adults with chronic pain were associated with decreased well-being and quality of life, and increased health care costs to society.

Strategy for nutrient control in modern effluent treatment plants.

The fate of nutrients in the modern effluent treatment plant depends on several factors, for example type of treatment plant, availability of nutrients in the specific effluent, dosing of nutrients and sludge age/production. New technologies with the aim to increase the efficiency and stability of the conventional activated sludge process have strongly affected the possibilities to control discharge of nutrients in pulp and paper effluents. A paradox is that a reduction of organic material may often lead to an increase of nutrient discharges. It is of the utmost importance that the operators have good knowledge of the factors affecting nutrient uptake and release in order to minimise nutrient discharge and obtain optimal plant performance. Dosing of nitrogen and phosphorus is one key factor in the sensitive balance in most pulp and paper effluent treatment plants. Correct dosing is crucial as high or low doses might lead not only to increased discharge of nutrients but also to severe operational problems with poor sludge quality, which in turn affects the plant performance for longer periods.

Illness beliefs among patients with chronic widespread pain - associations with self-reported health status, anxiety and depressive symptoms and impact of pain.

BACKGROUND: Chronic widespread pain (CWP) is a disabling condition associated with a decrease in health. Illness beliefs are individual and are acquired during life. Constraining beliefs may prevent patients from regaining health. Understanding these patients' illness beliefs may be a way to improve the health care they are offered. The aim of this study was to describe illness beliefs among patients with CWP and associations with self-reported health, anxiety and depressive symptoms, and impact of pain. METHOD: In this cross-sectional study, questionnaires were sent by mail to 330 patients including socio-demographic information, the Illness Perception Questionnaire (IPQ-R), the Short-Form General Health Survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS). Data were analysed using descriptive statistics, non-parametric tests and linear regression analyses. RESULTS: Patients experienced and related a high number of symptoms to CWP (mean (SD) 9 (3)). The patients believed their illness to be long lasting, to affect their emotional well being, and to have negative consequences for their lives. Some 72% reported having severe or very severe pain, and impact of pain according to SF-36 was negatively correlated to several illness beliefs dimensions, anxiety- and depressive symptoms. In regression analyses, the Identity, Consequences and Personal control dimensions of IPQ-R and Anxiety- and Depressive symptoms explained 32.6-56.1% of the variance in the two component scores of SF-36. CONCLUSION: Constraining illness beliefs in patients with CWP are related to worse health status, especially in cases of high number of physical or mental symptoms, beliefs of negative consequences or the illness affecting them emotionally. Identification and understanding of these beliefs may reduce patients' suffering if they are taken into consideration in rehabilitation programs and in development of new evidence-based interventions aimed at increasing health in patients with CWP.

Untargeted screening for novel autoantibodies with prognostic value in first-episode psychosis.

Immunological and inflammatory reactions have been suggested to have a role in the development of schizophrenia, a hypothesis that has recently been supported by genetic data. The aim of our study was to perform an unbiased search for autoantibodies in patients with a first psychotic episode, and to explore the association between any seroreactivity and the development of a Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) disorder characterized by chronic or relapsing psychotic symptoms. We collected plasma samples from 53 patients when they were treated for their first-episode psychosis, and 41 non-psychotic controls, after which the patients were followed for a mean duration of 7 years. Thirty patients were diagnosed with schizophrenia, delusional disorder, schizoaffective disorder, bipolar disorder or a long-term unspecified nonorganic psychosis during follow-up, whereas 23 patients achieved complete remission. At the end of follow-up, plasma samples were analyzed for IgG reactivity to 2304 fragments of human proteins using a multiplexed affinity proteomic technique. Eight patient samples showed autoreactivity to the N-terminal fragment of the PAGE (P antigen) protein family (PAGE2B/PAGE2/PAGE5), whereas no such autoreactivity was seen among the controls. PAGE autoreactivity was associated with a significantly increased risk of being diagnosed with schizophrenia during follow-up (odds ratio 6.7, relative risk 4.6). An immunohistochemistry analysis using antisera raised against the N-terminal fragment stained an unknown extracellular target in human cortical brain tissue. Our findings suggest that autoreactivity to the N-terminal portion of the PAGE protein family is associated with schizophrenia in a subset of patients with first-episode psychosis.

Quantitative neutron capture radiography for studying the biodistribution of tumor-seeking boron-containing compounds.

Biodistribution of two compounds presently considered for use in neutron capture therapy has been studied in mice carrying a transplantable Harding-Passey melanoma. A method is described by which quantitative assessment can be made of the boron distribution in whole-body sections of such animals. An alpha-particle-sensitive film is placed in close contact with a freeze-dried section of an animal and exposed to neutrons. The tracks visible after etching are analyzed optoelectronically in fields of 0.6 X 0.6 mm2 and compared to standards of boron homogeneously distributed in liver homogenates. The dynamic range of this method is about two orders of magnitude in concentration, with a lower detection limit of 0.1 to 0.01 ppm 10B, depending on the rate of induction of spurious tracks by fast neutrons present in the neutron beam chosen. In a transplantable Harding-Passey melanoma in mice, it was found that the sulfhydryl boron hydride Na2B12H11SH presently used for therapy of glioblastoma clears blood, muscle, and brain very rapidly. Its accumulation in tumors was persistent for more than three days. A higher tumor accumulation was observed with its disulfide, which has been suggested for neutron capture therapy. For both compounds, a marked heterogeneity of boron distribution within one tumor was found.

Prevalence of different pain categories based on pain spreading on the bodies of older adults in Sweden: a descriptive-level and multilevel association with demographics, comorbidities, medications, and certain lifestyle factors (PainS65+).

BACKGROUND AND OBJECTIVE: There is limited knowledge about the prevalence of pain and its relation to comorbidities, medication, and certain lifestyle factors in older adults. To address this limitation, this cross-sectional study examined the spreading of pain on the body in a sample of 6611 subjects ≥65 years old (mean age = 75.0 years; standard deviation [SD] = 7.7) living in southeastern Sweden. METHODS: Sex, age, comorbidities, medication, nicotine, alcohol intake, and physical activity were analyzed in relation to the following pain categories: local pain (LP) (24.1%), regional pain medium (RP-Medium) (20.3%), regional pain heavy (RP-Heavy) (5.2%), and widespread pain (WSP) (1.7%). RESULTS: RP-Medium, RP-Heavy, and WSP were associated more strongly with women than with men (all p<0.01). RP-Heavy was less likely in the 80-84 and >85 age groups compared to the 65-69 age group (both p<0.01). Traumatic injuries, rheumatoid arthritis/osteoarthritis, and analgesics were associated with all pain categories (all p<0.001). An association with gastrointestinal disorders was found in LP, RP-Medium, and RP-Heavy (all p<0.01). Depressive disorders were associated with all pain categories, except for LP (all p<0.05). Disorders of the central nervous system were associated with both RP-Heavy and WSP (all p<0.05). Medication for peripheral vascular disorders was associated with RP-Medium (p<0.05), and hypnotics were associated with RP-Heavy (p<0.01). CONCLUSION: More than 50% of older adults suffered from different pain spread categories. Women were more likely to experience greater spreading of pain than men. A noteworthy number of common comorbidities and medications were associated with increased likelihood of pain spread from LP to RP-Medium, RP-Heavy, and WSP. Effective management plans should consider these observed associations to improve functional deficiency and decrease spreading of pain-related disability in older adults.