Return to work after lumbar disc herniation surgery: an occupational cohort study

Background and purpose — Lumbar disc herniation is a common surgically treated condition in the working-age population. We assessed health-related risk factors for return to work (RTW) after excision of lumbar disc herniation. Previous studies on the subject have had partly contradictory findings. Patients and methods — RTW of 389 (n = 111 male, n = 278 female; mean age 46 years, SD 8.9) employees who underwent excision of lumbar disc herniation was assessed based on the Finnish Public Sector Study (FPS). Baseline information on occupation, preceding health, and health-risk behaviors was derived from linkage to national health registers and FPS surveys before the operation. The likelihood of RTW was analyzed using Cox proportional hazard univariable and multivariable modelling. Results — 95% of the patients had returned to work at 12 months after surgery, after on average 78 days of sickness absence. Faster RTW in the univariable Cox model was associated with a small number of sick leave days (< 30 days) before operation (HR 1.3, 95% CI 1.1–1.6); high occupational position (HR 1.6, CI 1.2–2.1); and age under 40 years (HR 1.5, CI 1.1–1.9). RTW was not associated with sex or the health-related risk factors obesity, physical inactivity, smoking, heavy alcohol consumption, poor self-rated health, psychological distress, comorbid conditions, or purchases of pain or antidepressant medications in either the univariable or multivariable model. Interpretation — Almost all employees returned to work after excision of lumbar disc herniation. Older age, manual job, and prolonged sick leave before the excision of lumbar disc herniation were risk factors for delayed return to work after the surgery

Return to work after lumbar disc herniation surgery : an occupational cohort study

Background and purpose - Lumbar disc herniation is a common surgically treated condition in the working-age population. We assessed health-related risk factors for return to work (RTW) after excision of lumbar disc herniation. Previous studies on the subject have had partly contradictory findings. Patients and methods - RTW of 389 (n = 111 male, n = 278 female; mean age 46 years, SD 8.9) employees who underwent excision of lumbar disc herniation was assessed based on the Finnish Public Sector Study (FPS). Baseline information on occupation, preceding health, and health-risk behaviors was derived from linkage to national health registers and FPS surveys before the operation. The likelihood of RTW was analyzed using Cox proportional hazard univariable and multivariable modelling. Results - 95% of the patients had returned to work at 12 months after surgery, after on average 78 days of sickness absence. Faster RTW in the univariable Cox model was associated with a small number of sick leave days (< 30 days) before operation (HR 1.3, 95% CI 1.1-1.6); high occupational position (HR 1.6, CI 1.2-2.1); and age under 40 years (HR 1.5, CI 1.1-1.9). RTW was not associated with sex or the health-related risk factors obesity, physical inactivity, smoking, heavy alcohol consumption, poor self-rated health, psychological distress, comorbid conditions, or purchases of pain or antidepressant medications in either the univariable or multivariable model. Interpretation - Almost all employees returned to work after excision of lumbar disc herniation. Older age, manual job, and prolonged sick leave before the excision of lumbar disc herniation were risk factors for delayed return to work after the surgery.Peer reviewe

Polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, intakes of folate and related B vitamins and colorectal cancer : a case-control study in a population with relatively low folate intake

Peer reviewedPublisher PD

Juicebox Provides a Visualization System for Hi-C Contact Maps with Unlimited Zoom

Hi-C experiments study how genomes fold in 3D, generating contact maps containing features as small as 20 bp and as large as 200 Mb. Here we introduce Juicebox, a tool for exploring Hi-C and other contact map data. Juicebox allows users to zoom in and out of Hi-C maps interactively, just as a user of Google Earth might zoom in and out of a geographic map. Maps can be compared to one another, or to 1D tracks or 2D feature sets.National Institutes of Health (U.S.) (NIH New Innovator Award (1DP2OD008540- 01))National Human Genome Research Institute (U.S.) ((NHGRI) Centers of Excellence in Genomic Science (P50HG006193))NVIDIA CorporationInternational Business Machines Corporation (IBM University Challenge Award)Google (Firm) (Google Research Award)Baylor College of Medicine (McNair Medical Institute Scholar Award)Cancer Prevention and Research Institute of Texas (Scholar Award (R1304))Presidential Early Career Award for Scientists and EngineersNational Science Foundation (U.S.) (NSF Physics Frontiers Centers (Center for Theoretical Biological Physics))Robert A. Welch FoundationNational Institute of General Medical Sciences (U.S.) (NIGMS R01GM074024)National Human Genome Research Institute (U.S.) (NHGRI (HG003067)

Hypoxia and tissue destruction in pulmonary TB.

BACKGROUND: It is unknown whether lesions in human TB are hypoxic or whether this influences disease pathology. Human TB is characterised by extensive lung destruction driven by host matrix metalloproteinases (MMPs), particularly collagenases such as matrix metalloproteinase-1 (MMP-1). METHODS: We investigated tissue hypoxia in five patients with PET imaging using the tracer [18F]-fluoromisonidazole ([18F]FMISO) and by immunohistochemistry. We studied the regulation of MMP secretion in primary human cell culture model systems in normoxia, hypoxia, chemical hypoxia and by small interfering RNA (siRNA) inhibition. RESULTS: [18F]FMISO accumulated in regions of TB consolidation and around pulmonary cavities, demonstrating for the first time severe tissue hypoxia in man. Patlak analysis of dynamic PET data showed heterogeneous levels of hypoxia within and between patients. In Mycobacterium tuberculosis (M.tb)-infected human macrophages, hypoxia (1% pO2) upregulated MMP-1 gene expression 170-fold, driving secretion and caseinolytic activity. Dimethyloxalyl glycine (DMOG), a small molecule inhibitor which stabilises the transcription factor hypoxia-inducible factor (HIF)-1α, similarly upregulated MMP-1. Hypoxia did not affect mycobacterial replication. Hypoxia increased MMP-1 expression in primary respiratory epithelial cells via intercellular networks regulated by TB. HIF-1α and NF-κB regulated increased MMP-1 activity in hypoxia. Furthermore, M.tb infection drove HIF-1α accumulation even in normoxia. In human TB lung biopsies, epithelioid macrophages and multinucleate giant cells express HIF-1α. HIF-1α blockade, including by targeted siRNA, inhibited TB-driven MMP-1 gene expression and secretion. CONCLUSIONS: Human TB lesions are severely hypoxic and M.tb drives HIF-1α accumulation, synergistically increasing collagenase activity which will lead to lung destruction and cavitation.Medical Research CouncilThis is the final version of the article. It first appeared from the British Medical Journal via https://doi.org/10.1136/thoraxjnl-2015-20740

A 3D Map of the Human Genome at Kilobase Resolution Reveals Principles of Chromatin Looping

SummaryWe use in situ Hi-C to probe the 3D architecture of genomes, constructing haploid and diploid maps of nine cell types. The densest, in human lymphoblastoid cells, contains 4.9 billion contacts, achieving 1 kb resolution. We find that genomes are partitioned into contact domains (median length, 185 kb), which are associated with distinct patterns of histone marks and segregate into six subcompartments. We identify ∼10,000 loops. These loops frequently link promoters and enhancers, correlate with gene activation, and show conservation across cell types and species. Loop anchors typically occur at domain boundaries and bind CTCF. CTCF sites at loop anchors occur predominantly (>90%) in a convergent orientation, with the asymmetric motifs “facing” one another. The inactive X chromosome splits into two massive domains and contains large loops anchored at CTCF-binding repeats.PaperFlic

Reversible Light-Induced Dimerization of Secondary Face Azobenzene-Functionalized β-Cyclodextrin Derivatives

β-cyclodextrin (βCyD) derivatives equipped with aromatic appendages at the secondary face exhibit tailorable self-assembling capabilities. The aromatic modules can participate in inclusion phenomena and/or aromatic-aromatic interactions. Supramolecular species can thus form that, at their turn, can engage in further co-assembling with third components in a highly regulated manner; the design of nonviral gene delivery systems is an illustrative example. Endowing such systems with stimuli responsiveness while keeping diastereomeric purity and a low synthetic effort is a highly wanted advancement. Here, we show that an azobenzene moiety can be “clicked” to a single secondary O-2 position of βCyD affording 1,2,3-triazole-linked βCyD-azobenzene derivatives that undergo reversible light-controlled self-organization into dimers where the monomer components face their secondary rims. Their photoswitching and supramolecular properties have been thoroughly characterized by UV-vis absorption, induced circular dichroism, nuclear magnetic resonance, and computational techniques. As model processes, the formation of inclusion complexes between a water-soluble triazolylazobenzene derivative and βCyD as well as the assembly of native βCyD/βCyD-azobenzene derivative heterodimers have been investigated in parallel. The stability of the host-guest supramolecules has been challenged against the competitor guest adamantylamine and the decrease of the medium polarity using methanol-water mixtures. The collective data support that the E-configured βCyD-azobenzene derivatives, in aqueous solution, form dimers stabilized by the interplay of aromatic-aromatic and aromatic-βCyD cavity interactions after partial reciprocal inclusion. Photoswitching to the Z-isomer disrupts the dimers into monomeric species, offering opportunity for the spatiotemporal control of the organizational status by light.Ministerio de Ciencia e Innovación PID2019-105858RB-I00, PID2020-118403GB-I00, PID2020-118384GB-I00, PID2020-119130GB-I00Fondo Europeo de Desarrollo Regional PID2021-124247OB-C21Junta de Andalucía P20_00166, US-1380698, P12-FQM-1467Universidad de Sevilla FPU18/02922, FPU19/0436

Return to work after lumbar disc herniation surgery: an occupational cohort study

Background and purpose - Lumbar disc herniation is a common surgically treated condition in the working-age population. We assessed health-related risk factors for return to work (RTW) after excision of lumbar disc herniation. Previous studies on the subject have had partly contradictory findings. Patients and methods - RTW of 389 (n = 111 male, n = 278 female; mean age 46 years, SD 8.9) employees who underwent excision of lumbar disc herniation was assessed based on the Finnish Public Sector Study (FPS). Baseline information on occupation, preceding health, and health-risk behaviors was derived from linkage to national health registers and FPS surveys before the operation. The likelihood of RTW was analyzed using Cox proportional hazard univariable and multivariable modelling. Results - 95% of the patients had returned to work at 12 months after surgery, after on average 78 days of sickness absence. Faster RTW in the univariable Cox model was associated with a small number of sick leave days (< 30 days) before operation (HR 1.3, 95% CI 1.1-1.6); high occupational position (HR 1.6, CI 1.2-2.1); and age under 40 years (HR 1.5, CI 1.1-1.9). RTW was not associated with sex or the health-related risk factors obesity, physical inactivity, smoking, heavy alcohol consumption, poor self-rated health, psychological distress, comorbid conditions, or purchases of pain or antidepressant medications in either the univariable or multivariable model. Interpretation - Almost all employees returned to work after excision of lumbar disc herniation. Older age, manual job, and prolonged sick leave before the excision of lumbar disc herniation were risk factors for delayed return to work after the surgery

Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression