DNA methylation and gene expression patterns in adipose tissue differ significantly within young adult monozygotic BMI-discordant twin pairs.

BACKGROUND: Little is known about epigenetic alterations associated with subcutaneous adipose tissue (SAT) in obesity. Our aim was to study genome-wide DNA methylation and gene expression differences in SAT in monozygotic (MZ) twin pairs who are discordant for body mass index (BMI). This design completely matches lean and obese groups for genetic background, age, gender and shared environment. METHODS: 14We analyzed DNA methylome and gene expression from SAT, together with body composition (magnetic resonance imaging/spectroscopy) and glucose tolerance test, lipids and C-reactive protein from 26 rare BMI-discordant (intrapair difference in BMI ⩾3 kg m(-2)) MZ twin pairs identified from 10 birth cohorts of young adult Finnish twins. RESULTS: We found 17 novel obesity-associated genes that were differentially methylated across the genome between heavy and lean co-twins. Nine of them were also differentially expressed. Pathway analyses indicated that dysregulation of SAT in obesity includes a paradoxical downregulation of lipo/adipogenesis and upregulation of inflammation and extracellular matrix remodeling. Furthermore, CpG sites whose methylation correlated with metabolically harmful fat depots (intra-abdominal and liver fat) also correlated with measures of insulin resistance, dyslipidemia and low-grade inflammation, thus suggesting that epigenetic alterations in SAT are associated with the development of unhealthy obesity. CONCLUSION: This is the first study in BMI-discordant MZ twin pairs reporting genome-wide DNA methylation and expression profiles in SAT. We found a number of novel genes and pathways whose methylation and expression patterns differ within the twin pairs, suggesting that the pathological adaptation of SAT to obesity is, at least in part, epigenetically regulated.

Biotin-dependent functions in adiposity: a study of monozygotic twin pairs.

BACKGROUND: Biotin acts as a coenzyme for carboxylases regulating lipid and amino-acid metabolism. We investigated alterations of the biotin-dependent functions in obesity and the downstream effects of biotin restriction in adipocytes in vitro. SUBJECTS: Twenty-four monozygotic twin pairs discordant for body mass index (BMI). Mean within-pair difference (heavy-lean co-twin, Δ) of BMI was 6.0 kg m(-2) (range 3.1-15.2 kg m(-)(2)). METHODS: Adipose tissue (AT) DNA methylation, gene expression of AT and adipocytes, and leukocytes (real-time quantitative PCR), serum biotin, C-reactive protein (CRP) and triglycerides were measured in the twins. Human adipocytes were cultured in low and control biotin concentrations and analyzed for lipid droplet content, mitochondrial morphology and mitochondrial respiration. RESULTS: The gene expression levels of carboxylases, PCCB and MCCC1, were upregulated in the heavier co-twins' leukocytes. ΔPCCB (r=0.91, P=0.0046) and ΔMCCC1 (r=0.79, P=0.036) correlated with ΔCRP within-pairs. Serum biotin levels were lower in the heavier (274 ng l(-1)) than in the lean co-twins (390 ng l(-1), P=0.034). ΔBiotin correlated negatively with Δtriglycerides (r=-0.56, P=0.045) within-pairs. In AT, HLCS and ACACB were hypermethylated and biotin cycle genes HLCS and BTD were downregulated (P<0.05). Biotin-dependent carboxylases were downregulated (ACACA, ACACB, PCCB, MCCC2 and PC; P<0.05) in both AT and adipocytes of the heavier co-twins. Adipocytes cultured in low biotin had decreased lipid accumulation, altered mitochondrial morphology and deficient mitochondrial respiration. CONCLUSIONS: Biotin-dependent functions are modified by adiposity independent of genetic effects, and correlate with inflammation and hypertriglyceridemia. Biotin restriction decreases lipid accumulation and respiration, and alters mitochondrial morphology in adipocytes.

Laboratory study of microphysical and scattering properties of corona-producing cirrus clouds.

Corona-producing cirrus clouds were generated and measured under chamber conditions at the AIDA cloud chamber in Karlsruhe. We were able to measure the scattering properties as well as microphysical properties of these clouds under well-defined laboratory conditions in contrast with previous studies of corona-producing clouds, where the measurements were conducted by means of lidar and in situ aircraft measurements. Our results are in agreement with those of previous studies, confirming that corona-producing cirrus clouds consist of a narrow distribution of small (median Dp=19-32 µm) and compact ice crystals. We showed that the ice crystals in these clouds are most likely formed in homogeneous freezing processes. As a result of the homogeneous freezing process, the ice crystals grow uniformly in size; furthermore, the majority of the ice crystals have rough surface features.

Prospective evaluation of external ocular microbial growth and aqueous humor contamination during cataract surgery.

PURPOSE: To analyze the route of aqueous humor contamination leading to the development of postoperative endophthalmitis. SETTING: Department of Ophthalmology, University of Helsinki, Finland. METHODS: Forty-nine eyes of 49 patients (31 having phacoemulsification and 18 extracapsular cataract extraction [ECCE]) participated in the study. Four bacterial cultures were taken: preoperative conjunctival swab, lid margin culture, intraoperative lacrimal lake sample, and immediate postoperative anterior chamber fluid sample. RESULTS: Preoperative lid margin cultures were positive in 59.2% of eyes, conjunctival cultures in 69.4%, and lacrimal lake cultures in 24.9%. Four aqueous humor samples (8.2%) showed bacterial growth in the anterior chamber aspirate: 3 in the phacoemulsification and 1 in the ECCE group. The bacteria isolated in this study, Staphylococcus epidermidis and Propionibacterium acnes (2 positive isolates each) were sensitive to the preoperative topical antibiotics used. No aqueous humor sample or any from other locations showed gram-negative microbe growth. The most frequently recovered microbes in all samples collected from the 3 other sources were S epidermidis and other coagulase-negative staphylococcus species, followed by P acnes and other propionibacterium species. Staphylococcus aureus, and diptheroids. CONCLUSION: The ocular surface significantly contributed to the transmission of microbes into the eye during cataract surgery. These microbes could not be eradicated by topical preoperative antibiotics. However, no patient developed postoperative endophthalmitis. Natural defense mechanisms appear to fend off a minor inoculum with these microbes of relatively low pathogenicity.

Relationship of subjective disability with pain intensity, pain duration, pain location, and work-related factors in nonoperated patients with chronic low back pain.

OBJECTIVE: A cross-sectional study on patients with chronic low back pain to compare relationships between subjective disability and pain intensity, pain duration, pain location, and work-related factors. DESIGN AND SUBJECTS: One hundred and seven outpatients with low back pain, with or without radiation to the legs, of at least 3 months' duration, were administered a comprehensive back patient questionnaire. The questionnaire included the Pain Disability Index (PDI) for the assessment of overall perceived disability and assessments of pain intensity, duration, and location and two pretested short-form work questionnaires. None of the patients had undergone a back operation. SETTING: Tertiary care center. RESULTS: There was evidence of significant interrelationships between the PDI and pain intensity (low back pain, r = 0.53, p < 0.001; leg pain, r = 0.32, p < 0.01; and buttock pain, r = 0.36, p < 0.01), pain location (significantly higher scores with distal pain radiation), and work-related factors (a work load sum score of r = 0.31, p < 0.01; significantly higher scores in patients on sick leave). CONCLUSIONS: The results suggest that subjective disability in patients with chronic low back pain overlaps with both pain and work-related factors. The observations support the multidimensionality of low back disability.

Relationship of the Pain Disability Index (PDI) and the Oswestry Disability Questionnaire (ODQ) with three dynamic physical tests in a group of patients with chronic low-back and leg pain.

OBJECTIVE: To determine the relationship between overall disability in daily activities, assessed with the Pain Disability Index (PDI) and the Oswestry Disability Questionnaire (ODQ), and impaired performance on three physical tests in patients with chronic low-back pain. DESIGN AND SUBJECTS: The PDI and ODQ were administered in a cross-sectional study, before beginning a back rehabilitation program, to 45 patients with low-back pain of > or = 3 months' duration, with or without radiation to the legs. All patients also performed repetitive sit-up, arch-up, and squatting tests. SETTING: Tertiary care center. RESULTS: Modestly significant (p < 0.05) or significant (p < 0.01) inverse correlations (Pearson's r = 0.30-0.41) were noted between the PDI and the ODQ and all three physical performance tests. When normative data were used, the correlation (Spearman's rs = -0.45) between PDI and the squatting test remained significant (p < 0.01), whereas it was modestly significant (rs = -0.33, p < 0.05) between the ODQ and squatting test and between the PDI and arch-up test (rs = -0.35, p < 0.05). Compared with patients presently working, those on sick leave had significantly higher scores on the PDI and ODQ (Wilcoxon's two-sample test: p < 0.001) and also significantly worse performance on all physical tests (p < 0.001). CONCLUSIONS: The PDI and ODQ, as measures of self-perceived disability, and impaired performance on repetitive squatting, arch-up, and sit-up tests, as measures of physical capability, show some overlap in low-back-pain patients. Both types of disability measures are clearly influenced by the patient's work status.

Intercorrelation and test-retest reliability of the Pain Disability Index (PDI) and the Oswestry Disability Questionnaire (ODQ) and their correlation with pain intensity in low back pain patients.

OBJECTIVE: To determine the intercorrelation between subjective disability, as assessed with the Pain Disability Index (PDI) and the Oswestry Disability Questionnaire (ODQ) and their correlation with visual analogue scale (VAS) pain intensity ratings. DESIGN AND SUBJECTS: Questionnaires were administered to 94 patients with chronic low back pain with or without radiation into the legs of at least 3 months' duration. SETTING: Tertiary care center. RESULTS: High correlations were noted between the ODQ and PDI (r = 0.83) and PDI factor 1 (r = 0.84), a subscale of the PDI. Lower correlations were noted between pain intensity (VAS) scores and the ODQ (r = 0.62) and the PDI (r = 0.69). A weaker correlation (r = 0.41) was noted between the ODQ and PDI factor 2. Intraclass correlation coefficients (ICC) for test-retest reliability in 20 patients (time interval 1 week) were for the ODQ ICC = 0.83, PDI ICC = 0.91, PDI percentage score ICC = 0.91, PDI factor 1 ICC = 0.87, and PDI factor 2 ICC = 0.73, respectively. CONCLUSIONS: The present results suggest that either the PDI or the percentage score PDI and also the even shorter-to-administer PDI factor 1 may be useful and reliable tests for the assessment of subjective disability in low back pain patients. As noted by the moderate intercorrelations with pain intensity scores, both the PDI and the ODQ address a broader concept of disability than that directly related to pain intensity.

Effect of zopiclone on sleep quality, morning stiffness, widespread tenderness and pain and general discomfort in primary fibromyalgia patients. A double-blind randomized trial.

Thirty-three patients fulfilling the diagnostic criteria for primary fibromyalgia completed an eight-week double-blind treatment trial with the drug zopiclone. Of outcome measures studied a score expressing subjective sleep quality showed improvement in more than ninety percent of zopiclone patients at 4 weeks and nearly eighty percent at 8 weeks, but similar improvement was also reported by more than sixty percent of the patients on placebo. Patient self-assessment of a treatment effect also showed an advantage for zopiclone, with most patients in the placebo group considering their state as unchanged at 8 weeks. According to examiner assessment, however, half the patients in both groups showed improvement at 8 weeks. For other assessment variables, e.g. dolorimeter assessment of widespread tenderness, visual analogue scales and pain drawings for pain and other subjective feelings of discomfort, the effects of zopiclone treatment were at the same level as those of placebo.

Early rehabilitation after small incision cataract surgery.

BACKGROUND: The use of smaller cataract incision is thought to induce less astigmatism, resulting in a more stable refraction and more stable wound. METHODS: We have analyzed the early astigmatic changes and rehabilitation in 20 eyes of 16 patients operated with advanced phacoemulsification techniques. The patients operated with small-incision surgery (incision 4.0 mm) were compared to those with large-incision surgery (incision 7.5 mm). Keratometric values and visual acuity data were evaluated up to 6 months postoperatively. RESULTS: Less initial induced astigmatism was demonstrated at day 7 postoperatively with a 4.0-millimeter incision (0.1 +/- 0.53 D) compared with a 7.5-millimeter incision (1.90 +/- 1.97). Similar but not statistically significant changes were seen at days 1 and 30 postoperatively. Visual rehabilitation was also faster in the small-incision group and 70% of the eyes gave uncorrected visual acuity of 20/40 or better in this group as early as the first postoperative day. Only 11% of the eyes showed that uncorrected visual acuity after large-incision surgery at first postoperative day. CONCLUSION: The low amount of induced cylinder, rapid stabilization of the wound, and faster visual rehabilitation confirms the advantage of small-incision cataract surgery to large-incision surgery.

Work load and individual factors affecting work ability among aging municipal employees.

The effects of work stressors, individual characteristics, symptoms, and diseases on work ability were studied among 4255 municipal employees. Work ability was assessed by a work ability index in two cross-sectional inquiries, one in 1981 and the other in 1985. The most impairing for work ability were mental symptoms and musculoskeletal disease. Among the work stressors, high physical demands at work, poor physical work environment, and lack of freedom were associated with impaired work ability. Muscular work, disturbing temperatures at the workplace, and lack of freedom particularly affected employees with disease, whereas poor work postures and role conflicts at work were particularly injurious for healthy employees. The worst situation was observed when a worker with many symptoms and disease was exposed to many different work stressors. Life satisfaction, sitting work posture, a good basic education, and physical exercise during leisure time were associated with good work ability.

Mortality, disability and changes in occupation among aging municipal employees.

During a four-year follow-up period the indicators of work load, individual factors, and stress reactions predicting mortality, disability, and change of occupation were studied. In 1981, 6257 active workers aged 44-58 years answered a questionnaire. The study was repeated in 1985 when 1% of the subjects had died, 9% had become disabled, and 5% had changed their occupation. These changes had occurred the most often in occupations which included muscular work, poor work postures, and a poor physical environment. The highest mortality rate was observed for the male installation and auxiliary workers who had reported the presence of cardiovascular, but no musculoskeletal, disease four years earlier. The highest disability rate was well predicted by a poor index of work ability. Major diseases leading to disability included malignant tumor, coronary artery disease, congestive heart failure, rheumatoid arthritis, bronchitis or bronchial asthma, and mental disease. Work-related stress reactions were associated with both mortality and disability.

Prevalence and incidence rates of diseases and work ability in different work categories of municipal occupations.

The purpose of this study was to determine the relationship between the health status and work ability of individuals representing a variety of municipal occupations. In both 1981 and 1985, 4255 employees answered a postal questionnaire. The subjects, aged 44-58 years in 1981, were grouped into physical, mental, or mixed physical and mental job categories. Occupational groups with a high disease prevalence in 1981 had a high, and occupational groups with a low disease prevalence in 1981 a low, disease incidence during the follow-up period. In 1985 every second subject suffered from a musculoskeletal disease. The highest disease prevalence was observed for physically demanding occupations and for men in work with mixed physical and mental demands. Female auxiliary workers, domestic helpers and cooks, and also male installation and transport workers, had the poorest health. The men and women in mental work had the best health and work ability.

Effect of retirement on health and work ability among municipal employees.

A questionnaire was sent to 6257 active employees, mean age 50.5 years, in 1981, and again in 1985, when 4255 of the workers were still actively working, 402 had retired because of age, and 468 had retired for medical reasons. After retirement, regardless of reason or previous work content, the prevalence of musculoskeletal diseases changed little among the women but increased markedly among the men retired from mental work. Among the men retired from mental work because of age, the prevalence of cardiovascular diseases increased after retirement. After disability pensioning the prevalence of cardiovascular diseases increased for both the men and the women. The prevalence of poor work ability increased in all the work categories irrespective of the type of retirement. Work ability did not improve after old-age pensioning, but health status was improved among the men and women in some occupational groups. Therefore light, part-time work should not be excluded for retired people.

Mortality and disability among cotton mill workers.

The mortality and disability of cotton mill workers were studied in five Finnish cotton mills. The population under study comprised all 1065 women exposed to raw cotton dust who had been hired between 1950 and 1971. The minimum exposure period was five years. For the study on disability, the cohort was followed up until the end of 1981. The follow up period for the mortality analysis was from 1950 to 1985. At the end of 1981 the observed number of prevalent disability pensions for respiratory disease was 15, whereas 3.9 were expected (p less than 0.01) on the basis of the national figures for women. There were 46 musculoskeletal diseases (27.7 expected, p less than 0.01), of which 24 were osteoarthritis (14.5 expected) and 13 rheumatoid arthritis (6.6 expected). The incidence rates of disability pensions were calculated for the period 1969-81. Comparison of incidence rates between cotton mill workers and the Finnish female population showed excessive rates for both respiratory diseases (p less than 0.001) and musculoskeletal diseases (p less than 0.01), with an excess of new cases of rheumatoid arthritis (p less than 0.05). By the end of 1985 the number of person-years was 31,678 and the number of deaths 95. The standardised mortality ratios for the total period of follow up (1950-85) showed no excess for respiratory diseases. Mortality from cardiovascular diseases was also lower than expected. The observed number of tumours was 33, the corresponding expected number 32.0. Thirteen tumours were in the digestive organs (6.6 expected, p<0.05) and three were lung cancers (1.9 expected). Five workers had died from renal disease; the expected number was 1.5 (p<0.05).

Cancer mortality of granite workers 1940-1985.

A retrospective cohort study was undertaken to investigate the cancer mortality of granite workers. The study comprised 1026 workers who took up such work between 1940 and 1971. The number of person-years was 23,434, and the number of deaths was 296. During the total follow-up period, 59 tumours were observed as compared with 54.4 expected. An excess mortality from tumours was observed in workers followed up for 20 years or more. Of the 59 tumours, 31 were lung cancers (expected 19.9), and 18 gastrointestinal cancers (expected 11.6), nine of which were stomach cancers (expected 7.1). Mortality from lung cancer was excessive for workers followed up for at least 15 years (28 observed, 12.7 expected). The results indicate that granite exposure per se may be an etiological factor in the initiation or promotion of malignant neoplasms.

An apparatus and a method for determining the slip resistance of shoes and floors by simulation of human foot motions.

An apparatus to measure the coefficient of kinetic friction (mu k) between the shoe sole and the underfoot surface was constructed, and a method including criteria to evaluate the risk of slipping during walking was developed. The apparatus is a prototype stationary step simulator capable of simulating the movements of a human foot and the forces applied to the underfoot surface during an actual slip, and the drainage capability of the contact surface between the shoe sole and the flooring when different lubricants or contaminants are used. The apparatus consists of a movable artificial foot controlled by a computer with the aid of three hydraulic cylinders. The frictional force (F mu), the normal force (FN) and their ratio (mu k = F mu/FN) are measured with a two-way force platform when the foot slides along its surface. Two separate gait patterns, heel-side (mu k 1) and sole-slide (mu k 2) gait pattern, are used for the evaluations. The method classifies studied shoe, lubricant and underfoot surface combinations into five slip resistance classes according to the measured mu k 1. The slip resistance assessments are specified with some complementary safety criteria, e.g., the ratio mu k 1/mu k 2. The reliability of the developed measurement method was assessed in an international comparison test. According to available results discussed in this paper, our method seems to be valid and the slip resistance measurements seem to be repeatable.

Silica exposure and rheumatoid arthritis: a follow up study of granite workers 1940-81.

The incidence and prevalence of subjects awarded disability pensions and the prevalence of subjects receiving free medicines because of rheumatoid arthritis were studied in a Finnish cohort of 1026 granite workers hired between 1940 and 1971 and followed up until 31 December 1981. The incidence of awards of disability pensions because of rheumatoid arthritis during 1969-81, the prevalence of rheumatoid arthritis on 31 December 1981, and the prevalence of subjects receiving free medicines for rheumatoid arthritis at the end of 1981 were significantly higher among the granite workers than in the general male population of the same age. Retrospective analysis of the records of all patients with rheumatoid arthritis in the cohort showed a predominance of a severe, serologically positive and erosive form of rheumatoid arthritis, usually with an age at onset of 50 or over. The possible aetiological or pathophysiological role of granite dust in rheumatoid arthritis may be based on the effects of quartz on the immune system.

Mortality and disability among granite workers.

The objective of the present study was to investigate the mortality, disability, and long-term morbidity of granite workers. The study included 1,026 workers hired between 1940 and 1971 and followed until the end of 1981. The total number of deaths was 235, and the expected number was 229.7. Excess mortality rates were observed for respiratory diseases (observed/expected = 28/13.9). The number of tumor deaths was 46 (expected 44.9). Excess lung cancer mortality was evident at 15 to 35 years of latency; the observed number of lung cancer deaths for the follow-up period of 25 to 29 years was 8, while 2.1 were expected. Mortality from cardiovascular diseases and violent deaths was slightly less than expected. The results for disability and long-term morbidity showed elevated incidence and prevalence rates for respiratory diseases and rheumatoid arthritis. The observed number of disability pensions due to rheumatoid arthritis in 1981 was 10 observed versus 1.8 expected, and the observed number of patients granted free medication was 19 versus 8.1 expected. The results indicate that granite dust exposure per se may be an etiologic and pathogenetic factor for lung cancer, cancer of the gastrointestinal tract, and some extrapulmonary nonmalignant chronic diseases.

Cancer mortality of granite workers.

A retrospective cohort study was undertaken to investigate the cancer mortality of granite workers. The study comprised 1,026 workers hired between 1940 and 1971. The number of person-years was 20,165, and the number of deaths 235. During the total follow-up 46 tumors were observed and 44.9 were expected. An excess mortality from tumors was observed for the workers followed for 20 years or more, the greatest excess occurring during the follow-up period of 25-29 years (observed 11, expected 5.2). Of the 46 tumors, 22 were lung cancers (expected 17.1) and 15 were gastrointestinal cancers (expected 9.7), nine of which were cancers of the stomach (expected 6.0). Mortality from lung cancer was excessive for workers with at least 15 years since entry into granite work (latency) (21 observed and 9.5 expected), being highest during the follow-up period of 25-29 years (observed 8, expected 2.1). The results indicate that granite exposure per se may be an etiologic factor in the initiation or promotion of malignant neoplasms.

Municipal employees' cardiovascular diseases and occupational stress factors in Finland.

The occupational stress factors related to specific cardiovascular diseases were studied by a questionnaire mailed to 6213 municipal employees aged 45 to 58 years, (response rate 85%) and by a specific job analysis of certain municipal occupations. The highest prevalences of self-reported chronic hypertension were found among male transport workers (19%), technical supervisors (19%) and auxiliary workers (15%), as well as among female domestic helpers (18%) and auxiliary workers (18%). Among men the prevalence of coronary heart disease varied from 9% for dump workers to 0% for dentists (mean 5%) and among women from 4% for kitchen supervisors to 0% for physicians (mean 3%). In the work profile groups with the highest rates of reported, specific cardiovascular diseases, the stress factors of women's work (domestic help and auxiliary work) were high energy demands, heavy dynamic and static work with high application of strength, poor postures, and uncomfortable climatic conditions. These stress factors were also typical among men doing auxiliary work. Other common stress factors among men included sensory-motor work done alone in static, monotonous sitting postures, exposured to vibration, drafts, and continuous alertness of the senses (transport work) and to processing and organization of information together with time pressure linked to decision-making and the need for accurate sensory perception (technical supervision work).