Trajectories of Occupational Cognitive Demands and Risk of Mild Cognitive Impairment and Dementia in Later Life: The HUNT4 70+ Study.

BACKGROUND AND OBJECTIVES: The cognitive reserve hypothesis posits that cognitively stimulating work delays the onset of mild cognitive impairment (MCI) and dementia. However, the effect of occupational cognitive demands across midlife on the risk of these conditions is unclear. METHODS: Using a cohort study design, we evaluated the association between registry-based trajectories of occupational cognitive demands from ages 30-65 years and clinically diagnosed MCI and dementia in participants in the HUNT4 70+ Study (2017-19). Group-based trajectory modeling identified trajectories of occupational cognitive demands, measured by the routine task intensity (RTI) index (lower RTI indicates more cognitively demanding occupation) from the Occupational Information Network. Multinomial regression was implemented to estimate the relative risk ratios (RRRs) of MCI and dementia, after adjusting for age, sex, education, income, baseline hypertension, obesity, diabetes, psychiatric impairment, hearing impairment, loneliness, smoking status, and physical inactivity assessed at HUNT1-2 in 1984-1986 and 1995-1997. To handle missing data, we used inverse probability weighting to account for nonparticipation in cognitive testing and multiple imputation. RESULTS: Based on longitudinal RTI scores for 305 unique occupations, 4 RTI trajectory groups were identified (n = 7,003, 49.8% women, age range 69-104 years): low RTI (n = 1,431, 20.4%), intermediate-low RTI (n = 1,578, 22.5%), intermediate-high RTI (n = 2,601, 37.1%), and high RTI (n = 1,393, 19.9%). Participants in the high RTI group had a higher risk of MCI (RRR 1.74, 95% CI 1.41-2.14) and dementia (RRR 1.37, 95% CI 1.01-1.86), after adjusting for age, sex, and education compared with participants in the low RTI group. In a sensitivity analysis, controlling for income and baseline health-related factors, the point estimates were not appreciably changed (RRR 1.66, 95% CI 1.35-2.06 for MCI, and RRR 1.31, 95% CI 0.96-1.78 for dementia). DISCUSSION: People with a history of cognitively stimulating occupations during their 30s, 40s, 50s, and 60s had a lower risk of MCI and dementia older than 70 years, highlighting the importance of occupational cognitive stimulation during midlife for maintaining cognitive function in old age. Further research is required to pinpoint the specific occupational cognitive demands that are most advantageous for maintaining later-life cognitive function.

Marital Histories and Associations With Later-Life Dementia and Mild Cognitive Impairment Risk in the HUNT4 70+ Study in Norway.

Objectives: Earlier studies suggest that being married in later life protects against dementia, and that being single in old age increases the risk of dementia. In this study, we examine midlife marital status trajectories and their association with dementia and mild cognitive impairment (MCI) at ages 70 plus using a large population based sample from Norway. Methods: Based on a general population sample linked to population registries (N = 8706), we used multinomial logistic regression to examine the associations between six types of marital trajectories (unmarried, continuously divorced, intermittently divorced, widowed, continuously married, intermittently married) between age 44 and 68 years from national registries and a clinical dementia or a MCI diagnosis after age 70. We estimated relative risk ratios (RRR) and used mediation analyses adjusting for education, number of children, smoking, hypertension, obesity, physical inactivity, diabetes, mental distress, and having no close friends in midlife. Inverse probability weighting and multiple imputations were applied. The population attributable fraction was estimated to assess the potential reduction in dementia cases due to marital histories. Results: Overall, 11.6% of the participants were diagnosed with dementia and 35.3% with MCI. Dementia prevalence was lowest among the continuously married (11.2%). Adjusting for confounders, the risk of dementia was higher for the unmarried (RRR = 1.73; 95% CI: 1.24, 2.40), continuously divorced (RRR = 1.66; 95% CI: 1.14, 2.43), and intermittently divorced (RRR = 1.50; 95% CI: 1.09, 2.06) compared to the continuously married. In general, marital trajectory was less associated with MCI than with dementia. In the counterfactual scenario, where all participants had the same risk of receiving a dementia diagnosis as the continuously married group, there would be 6.0% fewer dementia cases. Discussion: Our data confirm that staying married in midlife is associated with a lower risk of dementia and that divorced people account for a substantial share of dementia cases.

Elucidating the Role of O2 Uncoupling in the Oxidative Biodegradation of Organic Contaminants by Rieske Non-heme Iron Dioxygenases.

Oxygenations of aromatic soil and water contaminants with molecular O2 catalyzed by Rieske dioxygenases are frequent initial steps of biodegradation in natural and engineered environments. Many of these non-heme ferrous iron enzymes are known to be involved in contaminant metabolism, but the understanding of enzyme-substrate interactions that lead to successful biodegradation is still elusive. Here, we studied the mechanisms of O2 activation and substrate hydroxylation of two nitroarene dioxygenases to evaluate enzyme- and substrate-specific factors that determine the efficiency of oxygenated product formation. Experiments in enzyme assays of 2-nitrotoluene dioxygenase (2NTDO) and nitrobenzene dioxygenase (NBDO) with methyl-, fluoro-, chloro-, and hydroxy-substituted nitroaromatic substrates reveal that typically 20-100% of the enzyme's activity involves unproductive paths of O2 activation with generation of reactive oxygen species through so-called O2 uncoupling. The 18O and 13C kinetic isotope effects of O2 activation and nitroaromatic substrate hydroxylation, respectively, suggest that O2 uncoupling occurs after generation of FeIII-(hydro)peroxo species in the catalytic cycle. While 2NTDO hydroxylates ortho-substituted nitroaromatic substrates more efficiently, NBDO favors meta-substituted, presumably due to distinct active site residues of the two enzymes. Our data implies, however, that the O2 uncoupling and hydroxylation activity cannot be assessed from simple structure-reactivity relationships. By quantifying O2 uncoupling by Rieske dioxygenases, our work provides a mechanistic link between contaminant biodegradation, the generation of reactive oxygen species, and possible adaptation strategies of microorganisms to the exposure of new contaminants.

Substrate-Specific Coupling of O2 Activation to Hydroxylations of Aromatic Compounds by Rieske Non-heme Iron Dioxygenases.

Rieske dioxygenases catalyze the initial steps in the hydroxylation of aromatic compounds and are critical for the metabolism of xenobiotic substances. Because substrates do not bind to the mononuclear non-heme FeII center, elementary steps leading to O2 activation and substrate hydroxylation are difficult to delineate, thus making it challenging to rationalize divergent observations on enzyme mechanisms, reactivity, and substrate specificity. Here, we show for nitrobenzene dioxygenase, a Rieske dioxygenase capable of transforming nitroarenes to nitrite and substituted catechols, that unproductive O2 activation with the release of the unreacted substrate and reactive oxygen species represents an important path in the catalytic cycle. Through correlation of O2 uncoupling for a series of substituted nitroaromatic compounds with 18O and 13C kinetic isotope effects of dissolved O2 and aromatic substrates, respectively, we show that O2 uncoupling occurs after the rate-limiting formation of FeIII-(hydro)peroxo species from which substrates are hydroxylated. Substituent effects on the extent of O2 uncoupling suggest that the positioning of the substrate in the active site rather than the susceptibility of the substrate for attack by electrophilic oxygen species is responsible for unproductive O2 uncoupling. The proposed catalytic cycle provides a mechanistic basis for assessing the very different efficiencies of substrate hydroxylation vs unproductive O2 activation and generation of reactive oxygen species in reactions catalyzed by Rieske dioxygenases.

Effectiveness of an Annular Closure Device to Prevent Recurrent Lumbar Disc Herniation: A Secondary Analysis With 5 Years of Follow-up.

Importance: Patients with large annular defects following lumbar microdiscectomy for disc herniation are at increased risk for symptomatic recurrence and reoperation. Objective: To determine whether a bone-anchored annular closure device in addition to lumbar microdiscectomy resulted in lower reherniation and reoperation rates vs lumbar microdiscectomy alone. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial reports 5-year follow-up for enrolled patients between December 2010 and October 2014 at 21 clinical sites. Patients in this study had a large annular defect (6-10 mm width) following lumbar microdiscectomy for treatment of lumbar disc herniation. Statistical analysis was performed from November to December 2020. Interventions: Lumbar microdiscectomy with additional bone-anchored annular closure device (device group) or lumbar microdiscectomy only (control group). Main Outcomes and Measures: The incidence of symptomatic reherniation, reoperation, and adverse events as well as changes in leg pain, Oswestry Disability Index, and health-related quality of life when comparing the device and control groups over 5 years of follow-up. Results: Among 554 randomized participants (mean [SD] age: 43 [11] years; 327 [59%] were men), 550 were included in the modified intent-to-treat efficacy population (device group: n = 272; 270 [99%] were White); control group: n = 278; 273 [98%] were White) and 550 were included in the as-treated safety population (device group: n = 267; control group: n = 283). The risk of symptomatic reherniation (18.8% [SE, 2.5%] vs 31.6% [SE, 2.9%]; P < .001) and reoperation (16.0% [SE, 2.3%] vs 22.6% [SE, 2.6%]; P = .03) was lower in the device group. There were 53 reoperations in 40 patients in the device group and 82 reoperations in 58 patients in the control group. Scores for leg pain severity, Oswestry Disability Index, and health-related quality of life significantly improved over 5 years of follow-up with no clinically relevant differences between groups. The frequency of serious adverse events was comparable between the treatment groups. Serious adverse events associated with the device or procedure were less frequent in the device group (12.0% vs 20.5%; difference, -8.5%; 95% CI, -14.6% to -2.3%; P = .008). Conclusions and Relevance: In patients who are at high risk of recurrent herniation following lumbar microdiscectomy owing to a large defect in the annulus fibrosus, this study's findings suggest that annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation over 5 years of follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT01283438.

Genetic risks, adolescent health, and schooling attainment.

We provide new evidence on the effect of adolescent health behaviors/outcomes (obesity, depression, smoking, and attention deficit hyperactivity disorder [ADHD]) on schooling attainment using the National Longitudinal Study of Adolescent to Adult Health. We take two different approaches to deal with omitted variable bias and reverse causality. Our first approach attends to the issue of reverse causality by estimating the effect of health polygenic scores (PGSs) on schooling. Second, we estimate the effect of adolescent health using sibling fixed-effects models that control for unmeasured genetic and family factors shared by siblings. We use the PGSs as additional controls in the sibling fixed-effects models to reduce concerns about residual confounding from sibling-specific genetic differences. We find consistent evidence across both approaches that being genetically predisposed to smoking and smoking regularly in adolescence reduces schooling attainment. Estimates for depression are more imprecise, but also suggest that a high genetic risk of depression and adolescent depression reduce schooling attainment. We find mixed evidence for ADHD. Our estimates suggest that having a high genetic risk for ADHD reduces grades of schooling, but we do not find any statistically significant negative effects of ADHD. Finally, we find no consistent evidence for a detrimental effect of obesity on schooling attainment.

Health screening for emerging non-communicable disease burdens among the global poor: Evidence from sub-Saharan Africa.

Evidence for the effectiveness of population health screenings to reduce the burden of non-communicable diseases in low-income countries remains very limited. We investigate the sustained effects of a health screening in Malawi where individuals received a referral letter if they had elevated blood pressure. Using a regression discontinuity design and a matching estimator, we find that receiving a referral letter reduced blood pressure and the probability of being hypertensive by about 22 percentage points four years later. These lasting effects are explained by a 20 percentage points increase in the probability of being diagnosed with hypertension. There is also evidence of an increase in the uptake of medication, while we do not identify improvements in hypertension-related knowledge or risk behaviors. On the contrary, we find an increase in sugar intake and a decrease in physical activity both of which are considered risky behaviors in Western contexts. The health screening had some positive effects on mental health. Overall, this study suggests that population-based hypertension screening interventions are an effective tool to improve health in low-income contexts.

Annular closure device lowers reoperation risk 4 years after lumbar discectomy.

OBJECTIVE: To determine whether implanting an annular closure device (ACD) following a lumbar discectomy procedure in patients with large defects in the annulus fibrosus lowers the risk of reoperation after 4 years. METHODS: In a multicenter randomized trial, patients with large annular defects following single-level lumbar discectomy were intraoperatively randomized to additionally receive an ACD or no treatment (Controls). Clinical and imaging follow-up were performed at routine intervals over 4 years of follow-up. Main outcomes included reoperations at the treated lumbar level, leg pain scores on a visual analog scale, Oswestry Disability Index (ODI), and Physical Component Summary (PCS) and Mental Component Summary (MCS) scores from the SF-36 questionnaire. RESULTS: Among 550 patients (ACD 272, Control 278), the risk of reoperation over 4 years was 14.4% with ACD and 21.1% with Controls (P=0.03). The reduction in reoperation risk with ACD was not significantly influenced by patient age (P=0.51), sex (P=0.34), body mass index (P=0.21), smoking status (P=0.85), level of herniation (P=0.26), leg pain severity at baseline (P=0.90), or ODI at baseline (P=0.54). All patient-reported outcomes improved in each group from baseline to 4 years (all P<0.001). The percentage of patients who achieved the minimal clinically important difference without a reoperation was proportionally higher in the ACD group compared to Controls for leg pain (P=0.07), ODI (P=0.10), PCS (P=0.02), and MCS (P=0.06). CONCLUSION: The addition of a bone-anchored ACD following lumbar discectomy in patients with large post-surgical annular defects reduces the risk of reoperation and provides better long-term pain and disability relief over 4 years compared to lumbar discectomy only.

Annular closure in lumbar microdiscectomy for prevention of reherniation: a randomized clinical trial.

BACKGROUND CONTEXT: Patients with large annular defects after lumbar discectomy for disc herniation are at high risk of symptomatic recurrence and reoperation. PURPOSE: The present study aimed to determine whether a bone-anchored annular closure device, in addition to lumbar microdiscectomy, resulted in lower reherniation and reoperation rates plus increased overall success compared with lumbar microdiscectomy alone. DESIGN: This is a multicenter, randomized superiority study. PATIENT SAMPLE: Patients with symptoms of lumbar disc herniation for at least 6 weeks with a large annular defect (6-10 mm width) after lumbar microdiscectomy were included in the study. OUTCOME MEASURES: The co-primary end points determined a priori were recurrent herniation and a composite end point consisting of patient-reported, radiographic, and clinical outcomes. Study success required superiority of annular closure on both end points at 2-year follow-up. METHODS: Patients received lumbar microdiscectomy with additional bone-anchored annular closure device (n=276 participants) or lumbar microdiscectomy only (control; n=278 participants). This research was supported by Intrinsic Therapeutics. Two authors received study-specific support morethan $10,000 per year, 8 authors received study-specific support less than $10,000 per year, and 11 authors received no study-specific support. RESULTS: Among 554 randomized participants, 550 (annular closure device: n=272; control: n=278) were included in the modified intent-to-treat efficacy analysis and 550 (annular closure device: n=267; control: n=283) were included in the as-treated safety analysis. Both co-primary end points of the study were met, with recurrent herniation (50% vs. 70%, P<.001) and composite end point success (27% vs. 18%, P=.02) favoring annular closure device. The frequency of symptomatic reherniation was lower with annular closure device (12% vs. 25%, P<.001). There were 29 reoperations in 24 patients in the annular closure device group and 61 reoperations in 45 control patients. The frequency of reoperations to address recurrent herniation was 5% with annular closure device and 13% in controls (P=.001). End plate changes were more prevalent in the annular closure device group (84% vs. 30%, P<.001). Scores for back pain, leg pain, Oswestry Disability Index, and health-related quality of life at regular visits were comparable between groups over 2-year follow-up. CONCLUSIONS: In patients at high risk of herniation recurrence after lumbar microdiscectomy, annular closure with a bone-anchored implant lowers the risk of symptomatic recurrence and reoperation. Additional study to determine outcomes beyond 2 years with a bone-anchored annular closure device is warranted.

Isolation of the (+)-Pinoresinol-Mineralizing Pseudomonas sp. Strain SG-MS2 and Elucidation of Its Catabolic Pathway.

Pinoresinol is a dimer of two ß-ß'-linked coniferyl alcohol molecules. It is both a plant defense molecule synthesized through the shikimic acid pathway and a representative of several ß-ß-linked dimers produced during the microbial degradation of lignin in dead plant material. Until now, little has been known about the bacterial catabolism of such dimers. Here we report the isolation of the efficient (+)-pinoresinol-mineralizing Pseudomonas sp. strain SG-MS2 and its catabolic pathway. Degradation of pinoresinol in this strain is inducible and proceeds via a novel oxidative route, which is in contrast to the previously reported reductive transformation by other bacteria. Based on enzyme assays and bacterial growth, cell suspension, and resting cell studies, we provide conclusive evidence that pinoresinol degradation in strain SG-MS2 is initiated by benzylic hydroxylation, generating a hemiketal via a quinone methide intermediate, which is then hydrated at the benzylic carbon by water. The hemiketal, which stays in equilibrium with the corresponding keto alcohol, undergoes an aryl-alkyl cleavage to generate a lactone and 2-methoxyhydroquinone. While the fate of 2-methoxyhydroquinone is not investigated further, it is assumed to be assimilated by ring cleavage. The lactone is further metabolized via two routes, namely, lactone ring cleavage and benzylic hydroxylation via a quinone methide intermediate, as described above. The resulting hemiketal again exists in equilibrium with a keto alcohol. Our evidence suggests that both routes of lactone metabolism lead to vanillin and vanillic acid, which we show can then be mineralized by strain SG-MS2.IMPORTANCE The oxidative catabolism of (+)-pinoresinol degradation elucidated here is fundamentally different from the reductive cometabolism reported for two previously characterized bacteria. Our findings open up new opportunities to use lignin for the biosynthesis of vanillin, a key flavoring agent in foods, beverages, and pharmaceuticals, as well as various new lactones. Our work also has implications for the study of new pinoresinol metabolites in human health. The enterodiol and enterolactone produced through reductive transformation of pinoresinol by gut microbes have already been associated with decreased risks of cancer and cardiovascular diseases. The metabolites from oxidative metabolism we find here also deserve attention in this respect.

Bone-anchored annular closure following lumbar discectomy reduces risk of complications and reoperations within 90 days of discharge.

PURPOSE: The purpose of this study was to evaluate perioperative complications of lumbar discectomy with or without bone-anchored annular closure device (ACD) implant in patients at high risk of recurrent disc herniation. METHODS: This was a post hoc analysis of a randomized controlled trial that compared outcomes of lumbar discectomy with or without additional placement of an ACD. Patients presented with imaging evidence of lumbar disc herniation and radicular pain that was unresponsive to conservative care. Randomization occurred intraoperatively following discectomy completion and confirmation of annular defect width ≥6 mm. Main outcomes included serious adverse events (SAEs) from any cause, device- or procedure-related SAEs, and reoperations at the index level. The perioperative period included all outcomes occurring between the day of surgery and 90 days following hospital discharge. RESULTS: Analyses were performed on a modified intention-to-treat population consisting of 272 patients treated with ACD and 278 patients treated with lumbar discectomy only (controls). Mean patient age was 44 years, 59% were men, and mean body mass index was 26 kg/m2. Baseline patient characteristics and operative outcomes were comparable between groups. The risks of all-cause SAE (9.7% vs 16.3%, p=0.056), device- or procedure-related SAE (4.5% vs 10.2%, p=0.02), and index-level reoperation (1.9% vs 5.4%, p=0.03) were lower with ACD vs controls. In multivariable logistic regression, control group assignment and female gender were independently associated with higher risk of device- or procedure-related SAE and index-level reoperation, respectively. CONCLUSION: In patients undergoing lumbar discectomy to treat symptomatic intervertebral disc herniation, adjunctive placement of an ACD reduces the risk for perioperative complications occurring through 90 days following hospital discharge.

Cohort profile: internal migration in sub-Saharan Africa-The Migration and Health in Malawi (MHM) study.

PURPOSE: The Migration and Health in Malawi (MHM) study focuses on a key challenge in migration research: although it has long been established that migration and health are closely linked, identifying the effect of migration on various health outcomes is complicated by methodological challenges. The MHM study uses a longitudinal panel premigration and postmigration study design (with a non-migrant comparison group) to measure and/or control for important characteristics that affect both migration and health outcomes. PARTICIPANTS: Data are available for two waves. The MHM interviewed 398 of 715 migrants in 2007 (55.7%) and 722 of 1013 in 2013 (71.3%); as well as 604 of 751 (80.4%) for a non-migrant reference group in 2013. The total interviewed sample size for the MHM in both waves is 1809. These data include extensive information on lifetime migration, socioeconomic and demographic characteristics, sexual behaviours, marriage, household/family structure, social networks and social capital, HIV/AIDS biomarkers and other dimensions of health. FINDINGS TO DATE: Our result for the relationship between migration and health differs by health measure and analytic approach. Migrants in Malawi have a significantly higher HIV prevalence than non-migrants, which is primarily due to the selection of HIV-positive individuals into migration. We find evidence for health selection; physically healthier men and women are more likely to move, partly because migration selects younger individuals. However, we do not find differences in physical or mental health between migrants and non-migrants after moving. FUTURE PLANS: We are preparing a third round of data collection for these (and any new) migrants, which will take place in 2018. This cohort will be used to examine the effect of migration on various health measures and behaviours, including general mental and physical health, smoking and alcohol use, access to and use of health services and use of antiretroviral therapy.

Limited common origins of multiple adult health-related behaviors: Evidence from U.S. twins.

Health-related behaviors are significant contributors to morbidity and mortality in the United States, yet evidence on the underlying causes of the vast within-population variation in behaviors is mixed. While many potential causes of health-related behaviors have been identified-such as schooling, genetics, and environments-little is known on how much of the variation across multiple behaviors is due to a common set of causes. We use three separate datasets on U.S. twins to investigate the degree to which multiple health-related behaviors correlate and can be explained by a common set of factors. We find that aside from smoking and drinking, most behaviors are not strongly correlated among individuals. Based on the results of both within-identical-twins regressions and multivariate behavioral genetics models, we find some evidence that schooling may be related to smoking but not to the covariation between multiple behaviors. Similarly, we find that a large fraction of the variance in each of the behaviors is consistent with genetic factors; however, we do not find strong evidence that a single common set of genes explains variation in multiple behaviors. We find, however, that a large portion of the correlation between smoking and heavy drinking is consistent with common, mostly childhood, environments. This suggests that the initiation and patterns of these two behaviors might arise from a common childhood origin. Research and policy to identify and modify this source may provide a strong way to reduce the population health burden of smoking and heavy drinking.

Measurement of oxygen isotope ratios ((18)O/(16)O) of aqueous O2 in small samples by gas chromatography/isotope ratio mass spectrometry.

RATIONALE: Oxygen isotope fractionation of molecular O2 is an important process for the study of aerobic metabolism, photosynthesis, and formation of reactive oxygen species. The latter is of particular interest for investigating the mechanism of enzyme-catalyzed reactions, such as the oxygenation of organic pollutants, which is an important detoxification mechanism. METHODS: We developed a simple method to measure the δ(18) O values of dissolved O2 in small samples using automated split injection for gas chromatography coupled to isotope ratio mass spectrometry (GC/IRMS). After creating a N2 headspace, the dissolved O2 partitions from aqueous solution to the headspace, from which it can be injected into the gas chromatograph. RESULTS: In aqueous samples of 10 mL and in diluted air samples, we quantified the δ(18) O values at O2 concentrations of 16 µM and 86 µM, respectively. The chromatographic separation of O2 and N2 with a molecular sieve column made it possible to use N2 as the headspace gas for the extraction of dissolved O2 from water. We were therefore able to apply a rigorous δ(18) O blank correction for the quantification of (18) O/(16) O ratios in 20 nmol of injected O2 . CONCLUSIONS: The successful quantification of (18) O-kinetic isotope effects associated with enzymatic and chemical reduction of dissolved O2 illustrates how the proposed method can be applied for studying enzymatic O2 activation mechanisms in a variety of (bio)chemical processes.

Schooling has smaller or insignificant effects on adult health in the US than suggested by cross-sectional associations: new estimates using relatively large samples of identical twins.

Numerous theoretical reasons have been posited about why more schooling might improve health. Adult health outcomes and behaviors generally are significantly associated with schooling. However, such associations do not necessarily imply that schooling has causal effects on health outcomes and behaviors. Causal estimates based on schooling variation from policies and from within-MZ (monozygotic) twins have reached mixed conclusions. This study contributed new estimates of cross-sectional associations and within-MZ causal effects using three relatively large US twins samples. The estimates suggested that schooling was significantly associated with numerous health outcomes and behaviors. However, with within-MZ twins control for unobserved factors, schooling was no longer associated with most indicators of better health (with the exception of self-reported health), while it continued to be associated with outcomes such as fertility and spousal schooling. Similar patterns were observed for spousal schooling.

[Addiction patients in emergency departments]. / Suchtpatienten in der Notfallstation.

Addiction patients in emergency departments are common assignments from the rescue services. Often there are recurring images of the same patient. Patients with acute intoxications are passed from the emergency services in different constitution to the emergency department. The challenge to the treating emergency team and the infrastructure is correspondingly high. Nevertheless, the emergency treatment should include a comprehensive initial somatic and later psychosomatic treatment regim in these patients, this treatment option should always be offered and discussed again and again. Furthermore patients who are admitted to the hospital on emergency wards because of general medical or surgical problems, have in up to 10 % of cases a problematic behaviour with respect to their alcohol consumption, but are "compensated" at the time of entry. It is thus appropriate for all emergency patients who need to be hospitalized to perform a screening for a problematic alcohol consumption. there are appropriate questionnaires that take little time and can also be performed on emergency rooms, but you have to remember!

Bacterial ß-aminopeptidases: structural insights and applications for biocatalysis.

ß-Aminopeptidases comprise a class of enzymes with functional and structural similarities. All members of the ß-aminopeptidases described to date were isolated from bacterial sources. Uniquely, they catalyze the hydrolysis of ß(3) - and/or ß(2) -amino acid residues from amides and peptides that are otherwise considered proteolytically stable. Due to this unusual reactivity with ß-peptide substrates, ß-aminopeptidases have potential to be used as biocatalysts for ß-peptide synthesis and for the resolution of enantiomerically pure ß-amino acids from racemic substrate mixtures. ß-Aminopeptidases are formed from an inactive precursor by posttranslational autoproteolytic cleavage, exposing the catalytic nucleophile at the N-terminus of the newly formed ß-polypeptide chain. Such an activation step is a characteristic trait of enzymes of the N-terminal nucleophile (Ntn) hydrolase superfamily. However, classical Ntn hydrolases and ß-aminopeptidases differ by the fold of their catalytic cores and are hence likely to originate from distinct evolutionary ancestors. In this contribution, we review the existing literature on ß-aminopeptidases, including biochemical and functional studies, as well as structural investigations that recently allowed insights into the catalytic mechanisms of precursor processing and ß-peptide conversion.

D-dimers predict stroke subtype when assessed early.

BACKGROUND: Early classification of ischemic stroke subtype is important for secondary stroke prevention and may guide further investigations. METHODS: Levels of coagulation activation [fibrinopeptide A (FPA), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT)] and fibrinolysis activation [plasmin-alpha(2)-antiplasmin complex (PAP), D-dimers] markers were measured in 98 consecutive patients with a first-ever acute ischemic stroke admitted within 12 h after symptom onset. RESULTS: Median age was 67 years and 44% were women. Median time from symptom onset to blood sampling was 4 h. Stroke subtype was classified as 'cardioembolic' (54%), 'large-artery atherosclerosis' (11%), 'small-vessel disease' (5%), 'other determined' (9%) or 'undetermined etiology' (20%). Patients with cardioembolic stroke suffered more often from coronary artery disease than patients with other stroke etiologies (40 vs. 22%, p = 0.019). There were no differences in age, sex, stroke severity, time to blood sampling, frequency of hypertension, diabetes mellitus or current smoking. D-dimers (medians) were higher in patients with cardioembolic strokes than in those with other etiologies (615 vs. 322 microg/l, p < 0.001). No differences in F1+2, FPA, TAT or PAP levels were found. After multivariate analysis, higher D-dimer levels remained independently associated with cardioembolic stroke (p = 0.022). When measured within 6 h, D-dimers below 300 microg/l excluded cardioembolic stroke with a sensitivity of 100% and a specificity of 52%. CONCLUSIONS: Low D-dimer levels in the first few hours make a cardioembolic stroke unlikely, and may be useful to guide further investigations. Other coagulation markers were not useful in differentiating between different stroke etiologies.

Isomer-specific determination of 4-nonylphenols using comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry.

Technical nonylphenol (tNP), used for industrial production of nonylphenol polyethoxylate surfactants, is a complex mixture of C(3-10)-phenols. The major components, 4-nonylphenols, are weak endocrine disruptors whose estrogenicities vary according to the structure of the branched nonyl group. Thus, accurate risk assessment requires isomer-specific determination of 4-NPs. Comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC x GC/ToFMS) was used to characterize tNP samples obtained from seven commercial suppliers. Under optimal chromatographic conditions, 153-204 alkylphenol peaks, 59-66 of which were identified as 4-NPs, were detected. The 4-NPs comprised approximately 86-94% of tNP, with 2-NPs and decylphenols making up approximately 2-9% and approximately 2-5%, respectively. The tNP products were analyzed for eight synthetic 4-NP isomers, and results were compared with published data based on GC/MS analysis. Significant differences were found among the products and between two samples from a single supplier. The enhanced resolution of GC x GC coupled with fast mass spectral data acquisition by ToFMS facilitated identification of all major 4-NP isomers and a number of previously unrecognized components. Analysis of tNP altered by the bacterium, Sphingobium xenophagum Bayram, revealed several persistent 4-NPs whose structures and estrogenicities are presently unknown. The potential of this technology for isomer-specific determination of 4-NP isomers in environmental matrices is demonstrated using samples of wastewater-contaminated groundwater and municipal wastewater.

Sexual network structure and the spread of HIV in Africa: evidence from Likoma Island, Malawi.

BACKGROUND: Whereas sexual relationships among low-risk individuals account for the majority of HIV infections in sub-Saharan Africa, limited knowledge exists about the structure and characteristics of sexual networks among the general population in sub-Saharan Africa. OBJECTIVES: To investigate the population-level structure of sexual networks connecting the young adult population of several villages on Likoma Island (Malawi), and analyse the structural position of HIV-positive individuals within the sexual network. DESIGN AND METHODS: A cross-sectional sociocentric survey of sexual partnerships and biomarkers of prevalent HIV infections. RESULTS: The study documents the existence of a large and robust sexual network linking a substantial fraction of the island's young adult population: half of all sexually active respondents were connected in a giant network component, and more than a quarter were linked through multiple independent chains of sexual relationships. This high network connectivity emerges within short time frames. The prevalence of HIV also varied significantly across the network, with sparser regions having a higher HIV prevalence than densely connected components. Several risk factors related to sexual mixing patterns help explain differentials in HIV prevalence across network locations. CONCLUSION: Contrary to claims that sexual networks in rural sub-Saharan Africa are too sparse to sustain generalized HIV epidemics, the structure of the networks observed in Likoma appears compatible with a broad diffusion of HIV among lower-risk groups. The non-homogeneous distribution of HIV infection within the network suggests that network characteristics are an important determinant of the dynamics of HIV spread within a population.