Common pain conditions appear to have an adverse effect on work, but no comprehensive estimates exist on the amount of productive time lost in the US workforce due to pain.
To measure lost productive ...time (absence and reduced performance due to common pain conditions) during a 2-week period.
Cross-sectional study using survey data from the American Productivity Audit (a telephone survey that uses the Work and Health Interview) of working adults between August 1, 2001, and July 30, 2002.
Random sample of 28 902 working adults in the United States.
Lost productive time due to common pain conditions (arthritis, back, headache, and other musculoskeletal) expressed in hours per worker per week and calculated in US dollars.
Thirteen percent of the total workforce experienced a loss in productive time during a 2-week period due to a common pain condition. Headache was the most common (5.4%) pain condition resulting in lost productive time. It was followed by back pain (3.2%), arthritis pain (2.0%), and other musculoskeletal pain (2.0%). Workers who experienced lost productive time from a pain condition lost a mean (SE) of 4.6 (0.09) h/wk. Workers who had a headache had a mean (SE) loss in productive time of 3.5 (0.1) h/wk. Workers who reported arthritis or back pain had mean (SE) lost productive times of 5.2 (0.25) h/wk. Other common pain conditions resulted in a mean (SE) loss in productive time of 5.5 (0.22) h/wk. Lost productive time from common pain conditions among active workers costs an estimated 61.2 billion dollars per year. The majority (76.6%) of the lost productive time was explained by reduced performance while at work and not work absence.
Pain is an inordinately common and disabling condition in the US workforce. Most of the pain-related lost productive time occurs while employees are at work and is in the form of reduced performance.
The objective of this work was to determine the effects and implications of generic and site-specific aquatic eutrophication potential indicators in the Life Cycle Assessment (LCA) of livestock farm ...systems using a New Zealand (NZ) lake catchment case study.
Average dairy and sheep & beef farm systems in the Lake Taupo catchment were studied. Emissions of nitrogen (N) and phosphorus (P) to waterways, and ammonia and nitrogen oxides to air from these farms were calculated using the site-specific OVERSEER® nutrient budget model. These emissions data were then used to calculate the increase in nutrients in water bodies and aquatic Eutrophication indicators with a range of Life Cycle Impact Assessment (LCIA) methods.
Eutrophication indicator results varied considerably depending on the environmental mechanisms modelled by the LCIA method for the fate of N and P, accentuated by different choices for the inventory modelling. Using default emission factors instead of site-specific ones overestimated eutrophication impact results. The most recent methods are not only spatially-explicit and applicable beyond Europe, but they also account for more environmental mechanisms for the fate of the nutrients, giving relatively lower calculated impact results. However, the appropriate scale and spatial resolution is still a crucial question to address for these methods since they greatly affect results. Regarding eutrophication damage assessment, when the actual background nutrient concentration is very low, the end-point assessment method for freshwater eutrophication is not applicable. In this case, LCA fails to account for a high standard of water quality that is in a near-pristine state, but deteriorating.
The inventory of nutrient flows at a farm scale and fate factors modelled at a catchment scale should be site-specific. Freshwater eutrophication indicators should be based on a site-specific (and globally-valid) LCIA model rather than a generic one. Currently-accepted freshwater eutrophication indicators focus only on P, thus capturing only part of the problem for freshwater bodies that are co-limited by N and P (in terms of algal growth) such as Lake Taupo in NZ. Lake Taupo water quality concerns and regulations are not focused on P, but solely on N due to increasing N levels over time. Conclusions from this study are valid beyond NZ and beyond agricultural systems. Future work needs to investigate coupling N and P fate modelling based on the most recent globally-valid and spatially-explicit LCIA methods.
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•Eutrophication impact results varied considerably depending on the LCIA method.•Default emissions factors instead of site-specific ones overestimated impacts.•Eutrophication indicators focusing on one nutrient may not be relevant.•Freshwaters can be limited by N and P as shown here for New Zealand.•P effect modelling fails to account for high water quality standards and policy.
Pancreatic β cells are highly specialized to regulate systemic glucose levels by secreting insulin. In adults, increase in β-cell mass is limited due to brakes on cell replication. In contrast, ...proliferation is robust in neonatal β cells that are functionally immature as defined by a lower set point for glucose-stimulated insulin secretion. Here we show that β-cell proliferation and immaturity are linked by tuning expression of physiologically relevant, non-oncogenic levels of c-Myc. Adult β cells induced to replicate adopt gene expression and metabolic profiles resembling those of immature neonatal β that proliferate readily. We directly demonstrate that priming insulin-producing cells to enter the cell cycle promotes a functionally immature phenotype. We suggest that there exists a balance between mature functionality and the ability to expand, as the phenotypic state of the β cell reverts to a less functional one in response to proliferative cues.
Advanced in vitro culture from tissues of different origin includes three-dimensional (3D) organoid micro structures that may mimic conditions in vivo. One example of simple 3D culture is spheroids; ...ball shaped structures typically used as liver and tumour models. Oxygen is critically important in physiological processes, but is difficult to quantify in 3D culture: and the question arises, how small does a spheroid have to be to have minimal micro-environment formation? This question is of particular importance in the growing field of 3D based models for toxicological assessment. Here, we describe a simple non-invasive approach modified for the quantitative measurement and subsequent evaluation of oxygen gradients in spheroids developed from a non-malignant fish cell line (i.e. RTG-2 cells) using Electron Paramagnetic Resonance (EPR) oximetry. Sonication of the paramagnetic probe Lithium phthalocyanine (LiPc) allows for incorporation of probe particulates into spheroid during its formation. Spectra signal strength after incorporation of probe into spheroid indicated that a volume of 20 μl of probe (stock solution: 0.10 mg/mL) is sufficient to provide a strong spectra across a range of spheroid sizes. The addition of non-toxic probes (that do not produce or consume oxygen) report on oxygen diffusion throughout the spheroid as a function of size. We provide evidence supporting the use of this model over a range of initial cell seeding densities and spheroid sizes with the production of oxygen distribution as a function of these parameters. In our spheroid model, lower cell seeding densities (∼2,500 cells/spheroid) and absolute size (118±32 μm) allow control of factors such as pre-existing stresses (e.g. ∼ 2% normoxic/hypoxic interface) for more accurate measurement of treatment response. The applied methodology provides an elegant, widely applicable approach to directly characterize spheroid (and other organoid) cultures in biomedical and toxicological research.
To interrogate the pathogenesis of intrauterine growth restriction (IUGR) and apply Artificial Intelligence (AI) techniques to multi-platform i.e. nuclear magnetic resonance (NMR) spectroscopy and ...mass spectrometry (MS) based metabolomic analysis for the prediction of IUGR.
MS and NMR based metabolomic analysis were performed on cord blood serum from 40 IUGR (birth weight < 10th percentile) cases and 40 controls. Three variable selection algorithms namely: Correlation-based feature selection (CFS), Partial least squares regression (PLS) and Learning Vector Quantization (LVQ) were tested for their diagnostic performance. For each selected set of metabolites and the panel consists of metabolites common in three selection algorithms so-called overlapping set (OL), support vector machine (SVM) models were developed for which parameter selection was performed busing 10-fold cross validations. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity values were calculated for IUGR diagnosis. Metabolite set enrichment analysis (MSEA) was performed to identify which metabolic pathways were perturbed as a direct result of IUGR in cord blood serum.
All selected metabolites and their overlapping set achieved statistically significant accuracies in the range of 0.78-0.82 for their optimized SVM models. The model utilizing all metabolites in the dataset had an AUC = 0.91 with a sensitivity of 0.83 and specificity equal to 0.80. CFS and OL (Creatinine, C2, C4, lysoPC.a.C16.1, lysoPC.a.C20.3, lysoPC.a.C28.1, PC.aa.C24.0) showed the highest performance with sensitivity (0.87) and specificity (0.87), respectively. MSEA revealed significantly altered metabolic pathways in IUGR cases. Dysregulated pathways include: beta oxidation of very long fatty acids, oxidation of branched chain fatty acids, phospholipid biosynthesis, lysine degradation, urea cycle and fatty acid metabolism.
A systematically selected panel of metabolites was shown to accurately detect IUGR in newborn cord blood serum. Significant disturbance of hepatic function and energy generating pathways were found in IUGR cases.
Despite advances in molecularly characterizing glioblastoma (GBM), metabolic alterations driving its aggressive phenotype are only beginning to be recognized. Integrative cross-platform analysis ...coupling global metabolomic and gene expression profiling on patient-derived glioma identified fatty acid β-oxidation (FAO) as a metabolic node in GBM. We determined that the biologic consequence of enhanced FAO is directly dependent upon tumor microenvironment. FAO serves as a metabolic cue to drive proliferation in a β-HB/GPR109A dependent autocrine manner in nutrient favorable conditions, while providing an efficient, alternate source of ATP only in nutrient unfavorable conditions. Rational combinatorial strategies designed to target these dynamic roles FAO plays in gliomagenesis resulted in necroptosis-mediated metabolic synthetic lethality in GBM. In summary, we identified FAO as a dominant metabolic node in GBM that provides metabolic plasticity, allowing these cells to adapt to their dynamic microenvironment. Combinatorial strategies designed to target these diverse roles FAO plays in gliomagenesis offers therapeutic potential in GBM.
This study addresses a fundamental question in fish welfare: are the anaesthetics used for fish aversive? Despite years of routine general use of many agents, within both scientific research and ...aquaculture, there is a paucity of information regarding their tolerance and associated behavioural responses by fish. This study examined nine of the most commonly used fish anaesthetic agents, and performed preference tests using adult mixed sex zebrafish (Danio rerio), the most commonly held laboratory fish. Video tracking software quantified swimming behaviour related to aversion for each anaesthetic at 50% of its standard recommended dose compared with clean water in a flow-through chemotaxic choice chamber. Results suggest that several commonly used anaesthetics were aversive, including two of the most commonly recommended and used: MS222 (ethyl 3-aminobenzoate methanesulphate) and benzocaine. For ethical best practice, it is recommended that compounds that are aversive, even at low concentration, should no longer be used routinely for anaesthesia or indeed the first step of humane euthanasia of adult zebrafish. Two agents were found not to induce aversive behavioural responses: etomidate and 2,2,2 tribromoethanol. For the millions of adult zebrafish used in laboratories and breeding worldwide, etomidate appears best suited for future routine humane use.
We have re-investigated the structure and vibrational spectroscopy of the iconic molecule iron pentacarbonyl, Fe(CO)5, in the solid state by neutron scattering methods. In addition to the known C2/c ...structure, we find that Fe(CO)5 undergoes a displacive ferroelastic phase transition at 105 K to a P1̅ structure. We propose that this is a result of certain intermolecular contacts becoming shorter than the sum of the van der Waals radii, resulting in an increased contribution of electrostatic repulsion to these interactions; this is manifested as a strain that breaks the symmetry of the crystal. Evaluation of the strain in a triclinic crystal required a description of the spontaneous strain in terms of a second-rank tensor, something that is feasible with high-precision powder diffraction data but practically very difficult using strain gauges on a single crystal of such low symmetry. The use of neutron vibrational spectroscopy (which is not subject to selection rules) has allowed the observation of all the fundamentals below 700 cm–1 for the first time. This has resulted in the re-assignment of several of the modes. Surprisingly, density functional theory calculations that were carried out to support the spectral assignments provided a poor description of the spectra.
Background
The strikingly higher prevalence of migraine in females compared with males is one of the hallmarks of migraine. A large global body of evidence exists on the sex differences in the ...prevalence of migraine with female to male ratios ranging from 2 : 1 to 3 : 1 and peaking in midlife. Some data are available on sex differences in associated symptoms, headache‐related disability and impairment, and healthcare resource utilization in migraine. Few data are available on corresponding sex differences in probable migraine (PM) and other severe headache (ie, nonmigraine‐spectrum severe headache). Gaining a clear understanding of sex differences in a range of severe headache disorders may help differentiate the range of headache types. Herein, we compare sexes on prevalence and a range of clinical variables for migraine, PM, and other severe headache in a large sample from the US population.
Methods
This study analyzed data from the 2004 American Migraine Prevalence and Prevention Study. Total and demographic‐stratified sex‐specific, prevalence estimates of headache subtypes (migraine, PM, and other severe headache) are reported. Log‐binomial models are used to calculate sex‐specific adjusted prevalence ratios and 95% confidence intervals for each across demographic strata. A smoothed sex prevalence ratio (female to male) figure is presented for migraine and PM.
Results
One hundred sixty‐two thousand seven hundred fifty‐six individuals aged 12 and older responded to the 2004 American Migraine Prevalence and Prevention Study survey (64.9% response rate). Twenty‐eight thousand two hundred sixty‐one (17.4%) reported “severe headache” in the preceding year (23.5% of females and 10.6% of males), 11.8% met International Classification of Headache Disorders‐2 criteria for migraine (17.3% of females and 5.7% of males), 4.6% met criteria for PM (5.3% of females and 3.9% of males), and 1.0% were categorized with other severe headache (0.9% of females and 1.0% of males). Sex differences were observed in the prevalence of migraine and PM, but not for other severe headache. Adjusted female to male prevalence ratios ranged from 1.48 to 3.25 across the lifetime for migraine and from 1.22 to 1.53 for PM. Sex differences were also observed in associated symptomology, aura, headache‐related disability, healthcare resource utilization, and diagnosis for migraine and PM. Despite higher rates of migraine diagnosis by a healthcare professional, females with migraine were less likely than males to be using preventive pharmacologic treatment for headache.
Conclusions
In this large, US population sample, both migraine and PM were more common among females, but a sex difference was not observed in the prevalence of other severe headache. The sex difference in migraine and PM held true across age and for most other sociodemographic variables with the exception of race for PM. Females with migraine and PM had higher rates of most migraine symptoms, aura, greater associated impairment, and higher healthcare resource utilization than males. Corresponding sex differences were not observed among individuals with other severe headache on the majority of these comparisons. Results suggest that PM is part of the migraine spectrum whereas other severe headache types are not. Results also substantiate existing literature on sex differences in primary headaches and extend results to additional headache types and related factors.
Vulnerability to relapse during periods of attempted abstinence from cocaine use is hypothesized to result from the rewiring of brain reward circuitries, particularly ventral tegmental area (VTA) ...dopamine neurons. How cocaine exposures act on midbrain dopamine neurons to precipitate addiction-relevant changes in gene expression is unclear. We found that histone H3 glutamine 5 dopaminylation (H3Q5dop) plays a critical role in cocaine-induced transcriptional plasticity in the midbrain. Rats undergoing withdrawal from cocaine showed an accumulation of H3Q5dop in the VTA. By reducing H3Q5dop in the VTA during withdrawal, we reversed cocaine-mediated gene expression changes, attenuated dopamine release in the nucleus accumbens, and reduced cocaine-seeking behavior. These findings establish a neurotransmission-independent role for nuclear dopamine in relapse-related transcriptional plasticity in the VTA.
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