Narrative review of occupational exposures and noncommunicable diseases.

OBJECTIVE: Within the scope of the Exposome Project for Health and Occupational Research on applying the exposome concept to working life health, we aimed to provide a broad overview of the status of knowledge on occupational exposures and associated health effects across multiple noncommunicable diseases (NCDs) to help inform research priorities. METHODS: We conducted a narrative review of occupational risk factors that can be considered to have "consistent evidence for an association," or where there is "limited/inadequate evidence for an association" for 6 NCD groups: nonmalignant respiratory diseases; neurodegenerative diseases; cardiovascular/metabolic diseases; mental disorders; musculoskeletal diseases; and cancer. The assessment was done in expert sessions, primarily based on systematic reviews, supplemented with narrative reviews, reports, and original studies. Subsequently, knowledge gaps were identified, e.g. based on missing information on exposure-response relationships, gender differences, critical time-windows, interactions, and inadequate study quality. RESULTS: We identified over 200 occupational exposures with consistent or limited/inadequate evidence for associations with one or more of 60+ NCDs. Various exposures were identified as possible risk factors for multiple outcomes. Examples are diesel engine exhaust and cadmium, with consistent evidence for lung cancer, but limited/inadequate evidence for other cancer sites, respiratory, neurodegenerative, and cardiovascular diseases. Other examples are physically heavy work, shift work, and decision latitude/job control. For associations with limited/inadequate evidence, new studies are needed to confirm the association. For risk factors with consistent evidence, improvements in study design, exposure assessment, and case definition could lead to a better understanding of the association and help inform health-based threshold levels. CONCLUSIONS: By providing an overview of knowledge gaps in the associations between occupational exposures and their health effects, our narrative review will help setting priorities in occupational health research. Future epidemiological studies should prioritize to include large sample sizes, assess exposures prior to disease onset, and quantify exposures. Potential sources of biases and confounding need to be identified and accounted for in both original studies and systematic reviews.

Labour market trajectories after part-time sickness absence: a nationwide cohort study from Finland.

OBJECTIVES: The use of part-time sickness absence (pSA) enables return to part-time work from full sickness absence. However, subsequent labour market outcomes of pSA users depend on various individual and work-related characteristics. We investigated labour market paths of private and public sector employees after having a pSA spell. Moreover, we examined individual and work-related factors associated with following them. DESIGN: Longitudinal register-based cohort study. SETTING: Finnish employed population. PARTICIPANTS: 9896 receivers of partial sickness allowance aged 45-56 in the years 2010-2014. OUTCOME: We constructed labour market trajectories based on the proportion of time spent in various labour market statuses measured over 3 years after the end of the pSA spell using multiresponse trajectory analysis. We then examined how different individual and work-related factors were associated with assignment to the different trajectory groups using logistic regression analyses. RESULTS: The majority of the pSA users followed paths where work participation was consistently elevated (Sustained Work group, 40.4%), or only slightly reduced (Slightly Reduced Work group, 31.6%). Moreover, more than 1/10th of the users followed a path where receiving partial work disability benefits became predominant (Partial Work Disability group, 12.5%). The rest followed paths where other non-employment (Other Non-Employed group, 7.8%) or full work disability (Full Work Disability group, 7.7%) became the prevailing status. Lower educational level and income predicted assignment to all other groups than the Sustained Work group. Additional predictors were identified, yet these differed between the trajectory groups. CONCLUSIONS: The majority of the pSA users maintained a connection to working life, yet weaker working life paths were also identified. The paths were determined by various individual and work-related factors that can help health professionals and employers to better target support measures particularly towards individuals whose connection to working life is at risk to weaken after the use of pSA.

Calix[4]arene-pyrazole conjugates as potential cancer therapeutics.

Tumor selectivity is yet a challenge in chemotherapy-based cancer treatment. A series of calixarenes derivatized at the lower rim with 3-phenyl-1H-pyrazole units with variable upper-rim substituent and conformations of macrocyclic core, alkyl chain length between heterocycle and core, as well as phenolic monomer (5-(4-tert-butylphenyloxy)methoxy-3-phenyl-1H-pyrazole) have been synthesized and characterized in a range of therapeutically relevant cellular models (M-HeLa, MCF7, A-549, PC3, Chang liver, and Wi38) from different target organs/systems. Specific cytotoxicity for M-HeLa cells has been observed in tert-butylcalix[4]arene pyrazoles in 1,3-alternate (compound 7b) and partial cone (compound 7c) conformations with low mutagenicity and haemotoxicity and in vivo toxicity in mice. Compounds 7b,c have induced mitochondrial pathway of apoptosis of M-HeLa cells through caspase-9 activation preceded by the cell cycle arrest at G0/G1 phase. A concomitant overexpression of DNA damage markers in pyrazole-treated M-HeLa cells suggests that calixarene pyrazoles target DNA, which was supported by the presence of interactions between calixarenes and ctDNA at the air-water interface.

Aggregation, Cytotoxicity and DNA Binding in a Series of Calix[4]arene Amphiphile Containing Aminotriazole Groups.

The present work focuses on the study of the aggregation and complexing properties of calixarenes as potential DNA condensation agents for gene delivery. In the current study, 1,4-triazole derivatives of calix[4]arenes 7 and 8 containing monoammonium fragments were synthesized. The synthesized compound's structure was characterized by using various spectroscopic techniques (FTIR, HRESI MS, ¹H NMR and ¹³C NMR). The interactions between a series of calix[4]arene-containing aminotriazole groups (triazole-containing macrocycles with diethylenetriammonium fragments (3 and 4) and triazole-containing macrocycles with monoammonium fragments (7 and 8)) and calf thymus DNA were carried out via UV absorption, fluorescence spectroscopy, dynamic light scattering and zeta potential measurements. The role of the binding forces of calixarene-DNA complexes was analyzed. Photophysical and morphological studies revealed the interaction of the calixarenes 3, 4 and 8 with ct-DNA, which transformed the fibrous structure of ct-DNA to completely condensed compact structures that are 50 nm in diameter. The cytotoxic properties of calixarenes 3, 4, 7 and 8 against cancerous cells (MCF7, PC-3) as well as a healthy cell line (HSF) were investigated. Compound 4 was found to have the highest toxic effect on MCF7 breast adenocarcinoma (IC50 3.3 µM).

(2-Hydroxy-3-Methoxybenzylidene)thiazolo[3,2-a]pyrimidines: Synthesis, Self-Assembly in the Crystalline Phase and Cytotoxic Activity.

A series of new 2-hydroxy-3-methoxybenzylidenethiazolo[3,2-a]pyrimidines with different aryl substituents at the 5 position are synthesized and characterized by 1H/ 13C NMR and IR-spectroscopy and mass-spectrometry, as well as single crystal X-ray diffraction (SCXRD). It was demonstrated that the type of hydrogen bonding can play a key role in the chiral discrimination of these compounds in the crystalline phase. The hydrogen bond of the O-H...N type leads to 1D supramolecular heterochiral chains or conglomerate crystallization in the case of the formation of homochiral chains. The hydrogen bond of O-H...O type gave racemic dimers, which are packed into 2D supramolecular layers with a parallel or angular dimers arrangement. Halogen bonding of the N...Br or O...Br type brings a new motif into supramolecular self-assembly in the crystalline phase: the formation of 1D supramolecular homochiral chains instead 2D supramolecular layers. The study of cytotoxicity against various tumor cells in vitro was carried out. It was found that 2-hydroxy-3-methoxybenzylidenethiazolo[3,2-a]pyrimidines with 3-nitrophenyl substituent at C5 carbon atom demonstrated a high efficiency against M-HeLa (cervical adenocarcinoma) and low cytotoxicity against normal liver cells.

New Supramolecular Hypoxia-Sensitive Complexes Based on Azo-Thiacalixarene.

Hypoxia accompanies many human diseases and is an indicator of tumor aggressiveness. Therefore, measuring hypoxia in vivo is clinically important. Recently, complexes of calix[4]arene were identified as potent hypoxia markers. The subject of this paper is new hypoxia-sensitive host-guest complexes of thiacalix[4]arene. We report a new high-yield synthesis method for thiacalix[4]arene with four anionic carboxyl azo fragments on the upper rim (thiacalixarene L) and an assessment of the complexes of thiacalixarene L with the most widespread cationic rhodamine dyes (6G, B, and 123) sensitivity to hypoxia. Moreover, 1D and 2D NMR spectroscopy data support the ability of the macrocycles to form complexes with dyes. Rhodamines B and 123 formed host-guest complexes of 1:1 stoichiometry. Complexes of mixed composition were formed with rhodamine 6G. The association constant between thiacalixarene L and rhodamine 6G is higher than for other dyes. Thiacalixarene L-dye complexes with rhodamine 6G and rhodamine B are stable in the presence of various substances present in a biological environment. The UV-VIS spectrometry and fluorescence showed hypoxia responsiveness of the complexes. Our results demonstrate that thiacalixarene L has a stronger binding with dyes compared with the previously reported azo-calix[4]arene carboxylic derivative. Thus, these results suggest higher selective visualization of hypoxia for the complexes with thiacalixarene L.

Working life expectancy and working years lost among users of part- and full-time sickness absence in Finland.

OBJECTIVES: The use of part-time sickness absence (pSA) instead of full-time sickness absence (fSA) is known to increase work participation. Yet, its effect on the total length of working lives remains unclear. We carried out a quasi-experiment to assess the impact of using pSA versus fSA on the length of working lives. METHODS: We used a register-based 70% random sample of the working-age population living in Finland on 31 December 2007 to (i) form propensity-score-matched groups of users of pSA and fSA and (ii) calculate their working life expectancy (WLE) and working years lost (WYL). We applied the Sullivan method based on daily measured time spent at work and other labor market statuses, followed up over a four-year period until the end of year 2017. The study population consisted of private and public sector employees with SA due to mental and musculoskeletal disorders, ie, the diagnostic groups where pSA has been primarily used. RESULTS: Among both genders, the pSA group had a significantly higher WLE at age 30 than the fSA group, with larger differences seen in mental disorders compared to musculoskeletal diseases and in the private versus public sector. Overall, the pSA group had fewer WYL due to unemployment and disability retirement but more expected years working with partial disability benefits than the fSA group. CONCLUSIONS: Based on beneficial working career effects, the use of pSA instead of fSA should always be recommended for persons with mental or musculoskeletal disorders where feasible.

Synthesis, Self-Assembly in Crystalline Phase and Anti-Tumor Activity of 2-(2-/4-Hydroxybenzylidene)thiazolo[3,2-a]pyrimidines.

A series of new thiazolo[3,2-a]pyrimidines different by aryl substituents in 2 and 5 positions are synthesized and characterized in solution as well as in the crystalline phase using 1H and 13C NMR-, IR-spectroscopies, mass-spectrometry methods, and single crystal X-ray diffraction (SCXRD). The SCXRD study revealed the role of intermolecular H-bonding in the formation of supramolecular architectures (racemic monomers, centrosymmetric racematic dimers, or homochiral 1D chains) of obtained thiazolo[3,2-a]pyrimidines derivatives depending on solvents (aprotic DMSO or protic EtOH) used upon the crystallization process. Moreover, the in vitro study of cytotoxicity toward different tumor cells showed their high or moderate efficiency with moderate cytotoxicity against normal liver cells which allows to consider the obtained thiazolo[3,2-a]pyrimidine derivatives as promising candidates for application as antitumor agents.

Selective gas adsorption by calixarene-based porous octahedral M32 coordination cages.

Giant octahedral M32 coordination cages were prepared via self-assembly of sulfonylcalix[4]arene-supported tetranuclear M(II) clusters (M = Co, Ni) with hybrid linker based on tris(dipyrrinato)cobalt(III) complexes appended with peripherical carboxylic groups. Due to intrinsic and extrinsic porosity, the obtained solid-state supramolecular architectures demonstrated good performance as adsorbents for the separation of industrially important gases mixtures.

16S rRNA gene sequencing data of the upper respiratory tract microbiome in the SARS-CoV-2 infected patients.

The SARS-CoV-2 pandemic is a big challenge for humanity. The COVID-19 severity differs significantly from patient to patient, and it is important to study the factors protecting from severe forms of the disease. Respiratory microbiota may influence the patient's susceptibility to infection and disease severity due to its ability to modulate the immune system response of the host organism. This data article describes the microbiome dataset from the upper respiratory tract of SARS-CoV-2 positive patients from Russia. This dataset reports the microbial community profile of 335 human nasopharyngeal swabs collected between 2020-05 and 2021-03 during the first and the second epidemic waves. Samples were collected from both inpatients and outpatients in 4 cities of the Russian Federation (Moscow, Kazan, Irkutsk, Nizhny Novgorod) and sequenced using the 16S rRNA gene amplicon sequencing of V3-V4 region. Data contains information about the patient such as age, sex, hospitalization status, percent of damaged lung tissue, oxygen saturation (SpO2), respiratory rate, need for supplemental oxygen, chest computer tomography severity score, SARS-CoV-2 lineage, and also information about smoking and comorbidities. The amplicon sequencing data were deposited at NCBI SRA as BioProject PRJNA751478.

Associations of employment sector and occupational exposures with full and part-time sickness absence: random and fixed effects analyses on panel data.

OBJECTIVE: We aimed to investigate the influence of unobserved individual characteristics in explaining the effects of work-related factors on full (fSA) and part-time sickness absence (pSA). METHODS: We used register-based panel data for the period 2005-2016 on a 70% random sample of the Finnish working-age population. The relationships between employment sector and occupational exposures (% exposed to physically heavy work and job control score based on job exposure matrices) and the annual onset of fSA and pSA were investigated among men and women. First, random effects (RE) models were applied controlling for observed sociodemographic factors and then fixed effects (FE) models that examine within-individual changes over time and thereby further account for unobserved time-invariant individual characteristics. RESULTS: In the RE analyses, public employment sector, physically heavy work and lower job control each increased the use of fSA and pSA among both genders. When unobserved individual characteristics were controlled for with the FE models, the effects on fSA attenuated. For pSA, the effects of employment sector and physical heaviness of work among women even reversed. The effect of lower job control on pSA remained especially among women. CONCLUSIONS: The role of individuals' unobserved characteristics in explaining the effects of work-related factors on SA should not be neglected. The effects of work-related factors are likely to be overestimated when using traditional approaches that do not account for unobserved confounding, ie, selection of individuals with a high likelihood of SA into particular work environments.

The prevalence of occupational exposure to ergonomic risk factors: A systematic review and meta-analysis from the WHO/ILO Joint Estimates of the Work-related Burden of Disease and Injury.

BACKGROUND: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large network of experts. Evidence from mechanistic and human data suggests that occupational exposure to ergonomic (or physical) risk factors may cause osteoarthritis and other musculoskeletal diseases (excluding rheumatoid arthritis, gout, and back and neck pain). In this paper, we present a systematic review and meta-analysis of the prevalence of occupational exposure to physical ergonomic risk factors for estimating the number of disability-adjusted life years from these diseases that are attributable to exposure to this risk factor, for the development of the WHO/ILO Joint Estimates. OBJECTIVES: We aimed to systematically review and meta-analyse estimates of the prevalence of occupational exposure to ergonomic risk factors for osteoarthritis and other musculoskeletal diseases. DATA SOURCES: We searched electronic bibliographic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, EMBASE, and CISDOC. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference list of previous systematic reviews and included study records; and consulted additional experts. STUDY ELIGIBILITY AND CRITERIA: We included working-age (≥15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (<15 years) and unpaid domestic workers. The exposure was defined as any occupational exposure to one or more of: force exertion, demanding posture, repetitive movement, hand-arm vibration, kneeling or squatting, lifting, and/or climbing. We included all study types with an estimate of the prevalence of occupational exposure to ergonomic risk factors. STUDY APPRAISAL AND SYNTHESIS METHODS: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, followed by extraction of data from qualifying studies. We combined prevalence estimates using random-effect meta-analysis. Two or more review authors assessed the risk of bias and the quality of evidence, using the ROB-SPEO tool and QoE-SPEO approach developed specifically for the WHO/ILO Joint Estimates. RESULTS: Five studies (three cross-sectional studies and two cohort studies) met the inclusion criteria, comprising 150,895 participants (81,613 females) in 36 countries in two WHO regions (Africa, Europe). The exposure was generally assessed with questionnaire data about self-reported exposure. Estimates of the prevalence of occupational exposure to ergonomic risk factors are presented for all five included studies, disaggregated by country, sex, 5-year age group, industrial sector or occupational group where feasible. The pooled prevalence of any occupational exposure to ergonomic risk factors was 0.76 (95% confidence interval 0.69 to 0.84, 3 studies, 148,433 participants, 35 countries in the WHO Europe region, I2 100%, low quality of evidence). Subgroup analyses found no statistically significant differences in exposure by sex but differences by age group, occupation and country. No evidence was found for publication bias. We assessed this body evidence to be of low quality, based on serious concerns for risk of bias due to exposure assessment only being based on self-report and for indirectness due to evidence from two WHO regions only. CONCLUSIONS: Our systematic review and meta-analysis found that occupational exposure to ergonomic risk factors is highly prevalent. The current body of evidence is, however, limited, especially by risk of bias and indirectness. Producing estimates for the burden of disease attributable to occupational exposure to ergonomic risk factors appears evidence-based, and the pooled effect estimates presented in this systematic review may perhaps be used as input data for the WHO/ILO Joint Estimates. Protocol identifier:https://doi.org/10.1016/j.envint.2018.09.053. PROSPERO registration number: CRD42018102631.

Discovery of derivatives of 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides: novel, hypoxia-selective HIF-1α inhibitors with strong antiestrogenic potency.

In this article, we describe the synthesis of 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides bearing cyclic diamine residues at positions 6 or 7; the synthesis is based on the nucleophilic substitution of halogens. All synthesized 6(7)-aminoquinoxaline-2-carbonitrile 1,4-dioxides 3-6 demonstrated higher cytotoxicity and hypoxia selectivity compared to the reference agent tirapazamine against breast adenocarcinoma cell lines (MCF7, MDA-MB-231). The structure and position of the diamine residue considerably affects the antiproliferative properties of the quinoxaline-2-carbonitrile 1,4-dioxides. The introduction of a halogen atom at position 7 in the quinoxaline ring of 4a considerably increases the cytotoxicity of compounds 5a and 6a under both normoxic and hypoxic conditions. However, the most hypoxia-selective derivatives were non-halogenated 7-aminosubstituted 3-phenylquinoxaline-2-carbonitrile 1,4-dioxides 3a-j. Of the 32 novel synthesized derivatives, approximately 20 of the 6(7)-amino-3-phenylquinoxaline-2-carbonitrile 1,4-dioxides demonstrated high antiproliferative potency against wild type leukemia cells K562 and drug-resistant subline K562/4 with the expression of p-glycoprotein (p-gp) compared to the reference agent doxorubicin, which exhibited one order of magnitude lower activity towards K562/4 cells than towards K562 cells. Lead compounds 5a and 3f inhibited HIF-1α expression and activity and induced apoptosis in hypoxic tumor cells, which was confirmed by poly(ADP-ribose)polymerase (PARP) cleavage. Moreover, 5a and 3f showed strong antiestrogenic potencies in MCF7 breast cancer cells. Thus, the described series of quinoxaline 1,4-dioxides has high anticancer potential and good aqueous solubility. Therefore, these compounds are promising for further drug development of hypoxia-targeted anticancer agents.

Prostate cancer screening using chemometric processing of GC-MS profiles obtained in the headspace above urine samples.

The development of screening methods for various types of cancer is of utmost importance as the early diagnostics of these diseases significantly increases the chances for patient's successful medical treatment and recovery. In this study we have developed the procedure for chromatographic profiling of urine samples based on solid-phase microextraction and GC-MS. 50 urine samples (20 from the patients with biopsy conformed prostate cancer and 30 from control group) were studied in the optimized experimental conditions. Application of chemometric classification algorithms such as k-nearest neighbors and partial least squares-discriminant analysis allowed construction of predictive models yielding very high sensitivity, specificity and accuracy values all close to 100%. This gives a good promise for further validation of this approach with a broader sample sets.

Occupational and non-occupational risk factors of sickness absence due to a shoulder lesion.

OBJECTIVES: To determine the associations of lifestyle factors and cumulative physical workload exposures with sickness absence (SA) due to a shoulder lesion and to calculate their population attributable fractions (PAF). METHODS: Our nationally representative cohort consisted of 4344 individuals aged 30-62 years who participated in the Finnish Health 2000 Survey. Education, smoking, chronic diseases and work exposures were assessed during interviews and leisure time physical activity with a questionnaire. Weight and height were measured. We followed the individuals for 15 years for the first SA due to a shoulder lesion. We used competing risk regression models. We calculated PAFs to assess the proportion of SA that was attributed to modifiable risk factors. RESULTS: In the entire study population, risk factors of SA were age, daily smoking, being exposed for more than 10 years to physically heavy work and being exposed for more than 10 years to at least two specific physical workload factors. The overall PAF for the modifiable risk factors was 49%. In men, number of specific cumulative exposures, obesity and daily smoking predicted SA with PAF values of 34%, 30% and 14%, respectively. Among women, being exposed for more than 10 years to physically heavy work, number of specific cumulative exposures and daily smoking accounted for 23%, 22% and 15% of SA, respectively. CONCLUSIONS: Reducing significantly prolonged exposure to physical workload factors, avoiding regular smoking in both genders and obesity in men has a high potential to prevent SA due to a shoulder lesion.

Exposure to heavy physical work from early to later adulthood and primary healthcare visits due to musculoskeletal diseases in midlife: a register linked study.

OBJECTIVES: To examine whether exposure to heavy physical work from early to later adulthood is associated with primary healthcare visits due to cause-specific musculoskeletal diseases in midlife. DESIGN: Prospective cohort study. SETTING: Nationally representative Young Finns Study cohort, Finland. PARTICIPANTS: 1056 participants of the Young Finns Study cohort. EXPOSURE MEASURE: Physical work exposure was surveyed in early (18-24 years old, 1986 or 1989) and later adulthood (2007 and 2011), and it was categorised as: 'no exposure', 'early exposure only', 'later exposure only' and 'early and later exposure'. PRIMARY AND SECONDARY OUTCOME MEASURES: Visits due to any musculoskeletal disease and separately due to spine disorders, and upper extremity disorders were followed up from national primary healthcare register from the date of the third survey in 2011 until 2014. RESULTS: Prevalence of any musculoskeletal disease during the follow-up was 20%, that for spine disorders 10% and that for upper extremity disorders 5%. Those with physically heavy work in early adulthood only had an increased risk of any musculoskeletal disease (risk ratio (RR) 1.55, 95% CI 1.05 to 2.28) after adjustment for age, sex, smoking, body mass index, physical activity and parental occupational class. Later exposure only was associated with visits due to any musculoskeletal disease (RR 1.46, 95% CI 1.01 to 2.12) and spine disorders (RR 2.40, 95% CI 1.41 to 4.06). Early and later exposure was associated with all three outcomes: RR 1.99 (95% CI 1.44 to 2.77) for any musculoskeletal disease, RR 2.43 (95% CI 1.42 to 4.14) for spine disorders and RR 3.97 (95% CI 1.86 to 8.46) for upper extremity disorders. CONCLUSIONS: To reduce burden of musculoskeletal diseases, preventive actions to reduce exposure to or mitigate the consequences of physically heavy work throughout the work career are needed.

Physical heaviness of work and sitting at work as predictors of mortality: a 26-year follow-up of the Helsinki Birth Cohort Study.

OBJECTIVES: To examine the relationships of late-career physical heaviness of work and sitting at work with mortality. A national-level job exposure matrix was used to determine the occupation-specific level of physical heaviness and sitting. DESIGN: Prospective cohort study between years 1990 and 2015. SETTING: Community. PARTICIPANTS: 5210 men and 4725 women from the Helsinki Birth Cohort Study with an occupational code at baseline (ages 45-57 years). PRIMARY AND SECONDARY OUTCOME MEASURES: Total, cardiovascular (International Classification of Diseases 10th Revision I00-I99), cancer (C00-C97) and external (S00-Y84) mortality. RESULTS: The exposures, physical heaviness and sitting had a non-linear, inverse relationship. During the 26-year follow-up, 1536 men and 759 women died. Among men, physical heaviness of work was positively associated and sitting at work was negatively associated with all-cause, cardiovascular and external cause mortality but they were not associated with cancer mortality. The HRs for men in the highest quartile of physical heaviness of work compared with men in the lowest quartile were 1.54 (1.31-1.80) for all-cause mortality, 1.70 (1.30-2.23) for cardiovascular mortality and 3.18 (1.75-5.78) for external cause mortality (adjusted for age and years of education). Compared with the lowest quartile, the HRs for the highest quartile of sitting at work among men were 0.71 (0.61-0.82) for all-cause mortality, 0.59 (0.45-0.77) for cardiovascular mortality and 0.38 (0.22-0.66) for external cause mortality. In women, neither physical heaviness of work nor sitting at work was associated with mortality. CONCLUSIONS: Men in physically heavy work at their late-work career are at higher risk of death than men in physically light work.

Risk Factors for Low Back Pain: A Population-Based Longitudinal Study.

OBJECTIVE: To identify risk factors for low back pain (LBP) and lumbar radicular pain and to assess whether obesity and exposure to workload factors modify the effect of leisure-time physical activity on LBP and lumbar radicular pain. METHODS: The population of this 11-year longitudinal study consists of a nationally representative sample of Finns ages ≥30 years (n = 3,505). The outcomes of the study were LBP and lumbar radicular pain for >7 days or for >30 days in the past 12 months at follow-up. RESULTS: LBP and lumbar radicular pain were more common in women than in men. LBP slightly declined with increasing age, while lumbar radicular pain increased with age. Abdominal obesity (defined by waist circumference) increased the risk of LBP (adjusted odds ratio [OR] 1.40 [95% confidence interval (95% CI) 1.16-1.68] for LBP >7 days and adjusted OR 1.41 [95% CI 1.13-1.76] for LBP >30 days) and general obesity (defined by body mass index) increased the risk of lumbar radicular pain (adjusted OR 1.44 [95% CI 1.12-1.85] for pain >7 days and adjusted OR 1.62 [95% CI 1.16-2.26] for pain >30 days). Smoking and strenuous physical work increased the risk of both LBP and lumbar radicular pain. Walking or cycling to work reduced the risk of LBP, particularly LBP for >30 days (adjusted OR 0.75 [95% CI 0.59-0.95]), with the largest reductions among nonabdominally obese individuals and among those not exposed to physical workload factors. Using vibrating tools increased the risk of lumbar radicular pain. CONCLUSION: Lifestyle and physical workload factors increase the risk of LBP and lumbar radicular pain. Walking and cycling may have preventive potential for LBP.

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates.

The synthesis of new calix[4]arenes adopting a cone stereoisomeric form bearing two or four azide fragments on the upper rim and water-soluble triazolyl amphiphilic receptors with two or four polyammonium headgroups via copper-catalyzed azide-alkyne cycloaddition reaction has been performed for the first time. It was found that the synthesized macrocycles form stable aggregates with hydrodynamic diameters between 150-200 nm and electrokinetic potentials about +40 to +60 mV in water solutions. Critical aggregation concentration (CAC) values were measured using a micelle method with pyrene and eosin Y as dye probes. The CAC values of tetraalkyl-substituted macrocycles 12a,b (5 µM for both) are significantly lower than those for dialkyl-substituted macrocycles 10a,b (790 and 160 µM, respectively). Premicellar aggregates of macrocycles 10a,b and 12a,b with the dye eosin Y were used for nucleotides sensing through a dye replacement procedure. It is unusual that disubstituted macrocycles 10a,b bind more effectively a less charged adenosine 5'-diphosphate (ADP) than adenosine 5'-triphosphate (ATP). A simple colorimetric method based on polydiacetylene vesicles decorated with 10b was elaborated for the naked-eye detection of ADP with a detection limit of 0.5 mM.

Risk factors for first hospitalization due to meniscal lesions - a population-based cohort study with 30 years of follow-up.

BACKGROUND: Meniscal lesions are among the most common injuries of the knee, yet limited epidemiologic data is available on their risk factors. We investigated the association of lifestyle factors and physical strenuousness of work on knee injuries with a focus on meniscal lesions. METHODS: We examined a nationally representative sample of persons aged 30 to 59 years, who participated in a comprehensive health examination (the Mini-Finland Health Survey). Subjects without any injury or osteoarthritis in the knee joint at baseline (n = 4713) were subsequently followed via the National Hospital Discharge Register up to 30 years. RESULTS: During the follow-up, 338 knee injuries were identified of which 224 were meniscal lesions. Obesity and regular leisure time physical exercise were associated with an increased risk of first hospitalization due to meniscal lesions (hazard ratio (HR) 1.62 and 95% confidence interval (CI) 1.06-2.48 and 1.53, 95% CI 1.05-2.23, respectively). The types of sports predicting the highest risk of meniscal lesions were ballgames, gymnastics and jogging. Physical strenuousness of work did not predict meniscal lesion. The hazard of other knee injury was increased among those reporting irregular or regular physical exercise at baseline (HR 1.64, 95% CI 1.03-2.64 and 1.88 CI 1.05-2.36, respectively). Smoking or alcohol intake were not associated with knee injuries. CONCLUSIONS: Better safety measures in high-risk sports and weight control would likely improve the prevention of meniscal lesions in populations.