The ACGIH TLV for lifting: Estimated TLVs for torso asymmetry beyond 30 degrees.

BACKGROUND: The American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Values (TLVs) for Lifting is a manual material handling (MMH) assessment method to identify weight limits that nearly all workers may be exposed to without developing work-related low back disorders (LBD). However, this assessment method only applies to lifting with the torso within 30° asymmetry of the sagittal plane. OBJECTIVE: Estimate TLV weight limits while lifting with torso asymmetry greater than 30° beyond the sagittal plane. METHODS: Lifting tasks were performed from various horizontal and vertical locations, at torso asymmetry angles of 0°, 15°, 30°, 45°, 60°, 75° and 90°, using ACGIH identified TLVs. Validated MMH assessment methods (NIOSH Lifting Equation, Ohio State University LBD Risk Model) were utilized to estimate TLVs at torso asymmetries greater than 30°. RESULTS: The current ACGIH TLVs resulted in low- to moderate-risk risk levels for torso asymmetries from 0° to 30°, and the risk incrementally increased as torso asymmetry increased to 90°. With the intention to keep the risk levels to that found at 30° torso asymmetry, lower TLV weight limits in the vertical and horizontal zones investigated were estimated for torso asymmetries from 45° to 90°. The resulting adjusted TLVs were consistent with weight limits identified for similar lifting conditions from other assessment methods that account for torso asymmetry. CONCLUSIONS: This research found current ACGIH-defined TLVs possess less than high-risk for LBD, and provided guidance to practitioners for reduced TLVs when torso asymmetry is greater than 30° from the sagittal plane.

The Price of Pain: Workers Compensation Costs for Musculoskeletal Claims in the State of Kansas, 2014-2022.

OBJECTIVE: The aim of the study is to describe cost and frequency of work-related musculoskeletal disorders in Kansas. METHODS: Data were provided by the Kansas Department of Labor and included all closed workers' compensation claims entailing indemnity and medical costs from 2014 to 2022. RESULTS: Work-related musculoskeletal disorder claims entailed a median total cost of $20,097. Medical comprised 48.4% of costs, indemnity 46.4%, and legal 5.2%. The most frequently injured and costliest body part was the shoulder. Manufacturing comprised 28.4% of claims, followed by health care and office. Lifting was the most common cause, generating 32.0% of claims. Education, transportation, and mining were among industries with above average claim rates. CONCLUSIONS: Very few studies use workers' compensation data to assess work-related musculoskeletal disorder costs. This study introduces a state not yet analyzed and presents more recent years of data than available in the literature.

Diversity of the microbiota communities found in the various regions of the intestinal tract in healthy individuals and inflammatory bowel diseases.

The severe and chronic inflammatory bowel diseases (IBD), Crohn disease and ulcerative colitis, are characterized by persistent inflammation and gut damage. There is an increasing recognition that the gut microbiota plays a pivotal role in IBD development and progression. However, studies of the complete microbiota composition (bacteria, fungi, viruses) from precise locations within the gut remain limited. In particular, studies have focused primarily on the bacteriome, with available methods limiting evaluation of the mycobiome (fungi) and virome (virus). Furthermore, while the different segments of the small and large intestine display different functions (e.g., digestion, absorption, fermentation) and varying microenvironment features (e.g., pH, metabolites), little is known about the biogeography of the microbiota in different segments of the intestinal tract or how this differs in IBD. Here, we highlight evidence of the differing microbiota communities of the intestinal sub-organs in healthy and IBD, along with method summaries to improve future studies.

A Potential Role for Gut Microbes in Mediating Effects of Omega-3 Fatty Acids in Inflammatory Bowel Diseases: A Comprehensive Review.

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) have been associated with several inflammatory conditions, including inflammatory bowel diseases (IBDs), and found to have an impact on gut microbiota. In fact, some randomized controlled studies suggest benefits to IBD patients, but others do not. Our aim was to review recent evidence on the effects of omega-3 on IBD and establish the contribution of the gut microbiome. Omega-3 mediate anti-inflammatory effects in IBD through various mechanisms, including suppression of NLR family pyrin domain-containing 3 (NLRP3) inflammasome, Toll-like receptor-4 (TLR4), and nucleotide-binding oligomerization domain 2 (NOD2) signaling; this results in the repression of the nuclear factor-kappa B (Nf-kB) pathway and the secretion of pro-inflammatory cytokines. Omega-3 can also affect gut microbiota and revert the bacterial community to patterns associated with healthy status by increasing short-chain fatty acid (SCFA)-producing bacteria and enhancing the mucosal gut barrier, thus promoting homeostasis. The combination of these immunoregulatory effects and anti-inflammation properties with the promotion of a balanced gut microbiome environment could suggest that omega-3 might benefit IBD patients. Considering the microbiota of IBD patients while using omega-3 might predict and improve omega-3 effectiveness. Combining omega-3 with bacteria-altering therapy, such as probiotics and fecal microbiota transplantation, may further enhance its efficacy; however, further studies are required to elucidate mechanisms and potential preventive or treatment roles of omega-3 in IBD.

Comparison of ACGIH lifting threshold limit values to validated low back disorder lifting assessment methods outcomes.

BACKGROUND: Work-related low back pain (LBP) increases the workforce disability and healthcare costs. This study evaluated the LBD risk level associated with handling the ACGIH TLVs in lifting tasks corresponding to various horizontal and vertical zones. OBJECTIVE: The aim of this study was to compare the low-risk ACGIH TLV to risk outcomes from various validated lifting assessment methods, including the OSU LBD Risk Model, NIOSH Lifting Equation, and LiFFT. METHODS: Twenty-four subjects were recruited for this study to perform various lifting conditions. The various ergonomic assessment methods were then used to obtain the risk assessment outcomes. RESULTS: The selected assessment methods showed that the ACGIH-defined TLVs are associated with less than high-risk for LBD for all the assessed tasks. The findings showed a moderate agreement (Kendall's W = 0.477) among the various assessment methods risk outcomes. The highest correlation (ρ= 0.886) was observed between the NIOSH Lifting Equation and LiFFT methods risk assessment outcomes. CONCLUSION: The findings showed that ACGIH-defined TLVs possesses less than high-risk for LBD. The outcomes of the selected ergonomic assessment methods moderately agree to each other.

Unfermented ß-fructan Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients.

BACKGROUND & AIMS: Inflammatory bowel diseases (IBD) are affected by dietary factors, including nondigestible carbohydrates (fibers), which are fermented by colonic microbes. Fibers are overall beneficial, but not all fibers are alike, and some patients with IBD report intolerance to fiber consumption. Given reproducible evidence of reduced fiber-fermenting microbes in patients with IBD, we hypothesized that fibers remain intact in select patients with reduced fiber-fermenting microbes and can then bind host cell receptors, subsequently promoting gut inflammation. METHODS: Colonic biopsies cultured ex vivo and cell lines in vitro were incubated with oligofructose (5 g/L), or fermentation supernatants (24-hour anaerobic fermentation) and immune responses (cytokine secretion [enzyme-linked immunosorbent assay/meso scale discovery] and expression [quantitative polymerase chain reaction]) were assessed. Influence of microbiota in mediating host response was examined and taxonomic classification of microbiota was conducted with Kraken2 and metabolic profiling by HUMAnN2, using R software. RESULTS: Unfermented dietary ß-fructan fibers induced proinflammatory cytokines in a subset of IBD intestinal biopsies cultured ex vivo, and immune cells (including peripheral blood mononuclear cells). Results were validated in an adult IBD randomized controlled trial examining ß-fructan supplementation. The proinflammatory response to intact ß-fructan required activation of the NLRP3 and TLR2 pathways. Fermentation of ß-fructans by human gut whole microbiota cultures reduced the proinflammatory response, but only when microbes were collected from patients without IBD or patients with inactive IBD. Fiber-induced immune responses correlated with microbe functions, luminal metabolites, and dietary fiber avoidance. CONCLUSION: Although fibers are typically beneficial in individuals with normal microbial fermentative potential, some dietary fibers have detrimental effects in select patients with active IBD who lack fermentative microbe activities. The study is publicly accessible at the U.S. National Institutes of Health database (clinicaltrials.gov identification number NCT02865707).

Recent advances in coiled-coil peptide materials and their biomedical applications.

Extensive research has gone into deciphering the sequence requirements for peptides to fold into coiled-coils of varying oligomeric states. More recently, additional signals have been introduced within coiled-coils to promote higher order assembly into biomaterials with a rich distribution of morphologies. Herein we describe these strategies for association of coiled-coil building blocks and biomedical applications. With many of the systems described herein having proven use in protein storage, cargo binding and delivery, three dimensional cell culturing and vaccine development, the future potential of coiled-coil materials to have significant biomedical impact is highly promising.

Co-assembled Coiled-Coil Peptide Nanotubes with Enhanced Stability and Metal-Dependent Cargo Loading.

Peptide nanotube biomaterials are attractive for their range of applications. Herein, we disclose the co-assembly of coiled-coil peptides, one with ligands for metal ions that demonstrate hierarchical assembly into nanotubes, with spatial control of the metal-binding ligands. Enhanced stability of the nanotubes to phosphate-buffered saline was successfully accomplished in a metal-dependent fashion, depending on the levels and placement of the ligand-containing coiled-coil peptide. This spatial control also allowed for site-specific labeling of the nanotubes with His-tagged fluorophores through the length of the tubes or at the termini, in a metal-dependent manner.

Influence of different passive shoulder exoskeletons on shoulder and torso muscle activation during simulated horizontal and vertical aircraft squeeze riveting tasks.

Aircraft manufacturing involves riveting utilizing squeeze riveting tools at heights from below elbow to overhead levels. This study assessed utilization of passive shoulder exoskeletons on shoulder and torso muscle activation during simulated squeeze riveting. Horizontal and vertical riveting tasks using squeeze riveting tools were performed by 16 aircraft workers wearing three different shoulder exoskeletons and a no-exoskeleton condition capturing electromyographic signals from shoulder and torso muscles. Exoskeletons reduced normalized EMG for the left anterior deltoid at both heights (6.6% and 15.7%), the right anterior deltoid (8.3%) and the right and left medial deltoid (9.3% and 8.9%) at the upper height for horizontal squeeze riveting. Exoskeletons reduced normalized EMG for the right and left anterior deltoids (7.0%-10.6%) and medial deltoids (1.3%-7.1%) within the upper zones during vertical squeeze riveting. Participants felt exoskeletons would be beneficial for squeeze riveting, however no preference was found among the exoskeletons used.

Molecular Detection of Non-O157 Shiga Toxin-Producing Escherichia coli (STEC) Directly from Stool Using Multiplex qPCR Assays.

Non-O157 Shiga toxin-producing E. coli (STEC) can cause outbreaks that have great economic and health impact. Since the implementation of STEC screening in Alberta in 2018, it is also essential to have a molecular serotyping method with faster turnaround time for cluster identification and surveillance purposes. This study sought to perform molecular serotyping of the top six non-O157 (O26, O45, O103, O111, O121 and O145) STEC serotypes directly from stools and enrichment broths compared to conventional methods on isolates. Multiplex, serotyping qPCR assays were used to determine sensitivity and specificity of the top six non-O157 STEC serotypes. Sensitivity and specificity were assessed for both singleplex and multiplex qPCR assays for comparison of the top six serotypes. Blinded stool specimens (n = 116) or broth samples (n = 482) submitted from frontline microbiology laboratories for STEC investigation were analyzed by qPCR. Both singleplex and multiplex assays were comparable, and we observed 100% specificity with a limit of detection of 100 colony-forming units per mL. Direct molecular serotyping from stool specimens mostly correlated (88%) with conventional serotyping of the cultured isolate. In cases of discordant serotypes, the top six non-O157 STEC mixed infections were identified and confirmed by culture and conventional serotyping. Detection of non-O157 STEC can be done directly from stool specimens using multiplex PCR assays with the ability to identify mixed infections, which would otherwise remain undetected by conventional serotyping of a single colony. This method can be easily implemented into a frontline diagnostic laboratory to enhance surveillance of non-O157 STEC, as more frontline microbiology laboratories move to culture independent assays.

Metagenomics Versus Metatranscriptomics of the Murine Gut Microbiome for Assessing Microbial Metabolism During Inflammation.

Shotgun metagenomics studies have improved our understanding of microbial population dynamics and have revealed significant contributions of microbes to gut homeostasis. They also allow in silico inference of the metagenome. While they link the microbiome with metabolic abnormalities associated with disease phenotypes, they do not capture microbial gene expression patterns that occur in response to the multitude of stimuli that constantly ambush the gut environment. Metatranscriptomics closes that gap, but its implementation is more expensive and tedious. We assessed the metabolic perturbations associated with gut inflammation using shotgun metagenomics and metatranscriptomics. Shotgun metagenomics detected changes in abundance of bacterial taxa known to be SCFA producers, which favors gut homeostasis. Bacteria in the phylum Firmicutes were found at decreased abundance, while those in phyla Bacteroidetes and Proteobacteria were found at increased abundance. Surprisingly, inferring the coding capacity of the microbiome from shotgun metagenomics data did not result in any statistically significant difference, suggesting functional redundancy in the microbiome or poor resolution of shotgun metagenomics data to profile bacterial pathways, especially when sequencing is not very deep. Obviously, the ability of metatranscriptomics libraries to detect transcripts expressed at basal (or simply low) levels is also dependent on sequencing depth. Nevertheless, metatranscriptomics informed about contrasting roles of bacteria during inflammation. Functions involved in nutrient transport, immune suppression and regulation of tissue damage were dramatically upregulated, perhaps contributed by homeostasis-promoting bacteria. Functions ostensibly increasing bacteria pathogenesis were also found upregulated, perhaps as a consequence of increased abundance of Proteobacteria. Bacterial protein synthesis appeared downregulated. In summary, shotgun metagenomics was useful to profile bacterial population composition and taxa relative abundance, but did not inform about differential gene content associated with inflammation. Metatranscriptomics was more robust for capturing bacterial metabolism in real time. Although both approaches are complementary, it is often not possible to apply them in parallel. We hope our data will help researchers to decide which approach is more appropriate for the study of different aspects of the microbiome.

Reversible crosslinked assembly of a trimeric coiled-coil peptide into a three-dimensional matrix for cell encapsulation and release.

Mimicking the extracellular matrix (ECM) continues to be a goal in the field of regenerative medicine. Herein, we report a modified trimeric GCN4 coiled-coil sequence containing three ligands for metal ions specifically positioned for crosslinked assembly (TriCross). In the presence of metal ions, TriCross assembles into a three-dimensional (3D) matrix with significant cavities to accommodate cells. The matrix was found to be stable in media with serum, and mild removal of the metal leads to disassembly. By assembling TriCross with a suspension of cells in media, the matrix encapsulates cells during the assembly process leading to high cell viability. Further disassembly under mild conditions allows for the release of cells from the scaffold. As such, this peptide-based material displays many of the characteristics necessary for successful 3D cell culture.

The Multifaceted Roles of Diet, Microbes, and Metabolites in Cancer.

Many studies performed to date have implicated select microbes and dietary factors in a variety of cancers, yet the complexity of both these diseases and the relationship between these factors has limited the ability to translate findings into therapies and preventative guidelines. Here we begin by discussing recently published studies relating to dietary factors, such as vitamins and chemical compounds used as ingredients, and their contribution to cancer development. We further review recent studies, which display evidence of the microbial-diet interaction in the context of cancer. The field continues to advance our understanding of the development of select cancers and how dietary factors are related to the development, prevention, and treatment of these cancers. Finally, we highlight the science available in the discussion of common misconceptions with regards to cancer and diet. We conclude this review with thoughts on where we believe future research should focus in order to provide the greatest impact towards human health and preventative medicine.

Comparison of Common Enrichment Broths Used in Diagnostic Laboratories for Shiga Toxin-Producing Escherichia coli.

Acute gastroenteritis caused by Shiga toxin-producing Escherichia coli (STEC) affects more than 4 million individuals in Canada. Diagnostic laboratories are shifting towards culture-independent diagnostic testing; however, recovery of STEC remains an important aspect of surveillance programs. The objective of this study was to compare common broth media used for the enrichment of STEC. Clinical isolates including O157:H7 as well as non-O157 serotypes were cultured in tryptic soy (TSB), MacConkey (Mac), and Gram-negative (GN) broths and growth was compared using culture on sheep's blood agar and real-time PCR (qPCR). In addition, a selection of the same isolates was spiked into negative stool and enriched in the same three broths, which were then evaluated using culture on CHROMagarTM STEC agar and qPCR. TSB was found to provide the optimal enrichment for growth of isolates with and without stool. The results from this study suggest that diagnostic laboratories may benefit from enriching STEC samples in TSB as a first line enrichment instead of GN or Mac.

Association of Ct Values from Real-Time PCR with Culture in Microbiological Clearance Samples for Shiga Toxin-Producing Escherichia coli (STEC).

Shiga toxin-producing Escherichia coli (STEC) are associated with acute gastroenteritis worldwide, which induces a high economic burden on both healthcare and individuals. Culture-independent diagnostic tests (CIDT) in frontline microbiology laboratories have been implemented in Alberta since 2019. The objectives of this study were to determine the association between gene detection and culture positivity over time using STEC microbiological clearance samples and also to establish the frequency of specimen submission. Both stx genes' amplification by real-time PCR was performed with DNA extracted from stool samples using the easyMAG system. Stools were inoculated onto chromogenic agar for culture. An association between gene detection and culture positivity was found to be independent of which stx gene was present. CIDT can provide rapid reporting with less hands-on time and technical expertise. However, culture is still important for surveillance and early cluster detection. In addition, stool submissions could be reduced from daily to every 3-5 days until a sample is negative by culture.

Nigericin Promotes NLRP3-Independent Bacterial Killing in Macrophages.

Altered microbiota has been associated with a number of diseases, including inflammatory bowel diseases, diabetes, and cancer. This dysregulation is thought to relate the host inflammatory response to enteric pathogens. Macrophages play a key role in host response to microbes and are involved in bacterial killing and clearance. This process is partially mediated through the potassium efflux-dependent, cytosolic, PYCARD-containing inflammasome protein complex. Surprisingly, we discovered an alternative mechanism for bacterial killing, independent of the NLRP3 inflammasome/PYCARD. Using the NLRP3 inflammasome-deficient Raw 264.7 and PYCARD-deficient J77 macrophages, which both lack PYCARD, we found that the potassium efflux activator nigericin enhances bacterial killing. Macrophage response to nigericin was examined by RT gene profiling and subsequent qPCR, which demonstrated altered expression of a series of genes involved in the IL-18 bacterial killing pathway. Based on our results we propose a model of bacterial killing, unrelated to NLRP3 inflammasome activation in macrophage cells. Improving understanding of the molecular pathways driving bacterial clearance within macrophage cells will aid in the development of novel immune-targeted therapeutics in a number of diseases.

Characteristics and Clinical Outcomes of Patients With Spontaneous Coronary Artery Dissection.

Background The goal of this study is to report the characteristics and long-term clinical outcomes of patients with spontaneous coronary artery dissection (SCAD) and to identify factors associated with recurrent SCAD . Methods and Results This is a retrospective cohort study that included patients who underwent coronary angiography for evaluation of acute myocardial infarction between 2006 and 2016. Among 26 598 patients hospitalized with a principal diagnosis of acute myocardial infarction, 208 (0.78%) were diagnosed with SCAD . Patients with SCAD were younger (49.0±11.6 versus 65.6±12.2 years) and more likely to be women (88.9% versus 31.6%). Atherosclerotic risk factors, such as hypertension, hyperlipidemia, obesity, and diabetes mellitus, were less prevalent. Median follow-up was 4.7 years. Mortality was lower in patients with SCAD (1-year mortality: 2.4% versus 8.8%; P<0.001). After using propensity score matching to control for differences in age, sex, and comorbidities, the difference in mortality was no longer present, suggesting that lower mortality in patients with SCAD is attributed primarily to their baseline characteristics. Recurrent SCAD occurred in 22 patients (10.6%). Multivariate Cox regression modeling showed concomitant fibromuscular dysplasia (hazard ratio, 5.1; 95% CI , 1.6-15.8; P=0.005) and migraine headaches (hazard ratio, 3.4; 95% CI , 1.4-8.4; P=0.008) to be associated with increased risk of recurrent SCAD . Conclusions Among patients with acute myocardial infarction, patients with SCAD have a lower risk of mortality, which is attributed primarily to their younger age, female sex, and low prevalence of atherosclerotic risk factors. Risk of recurrent SCAD persists years after the initial presentation. Patients with fibromuscular dysplasia and migraine are at higher risk for recurrent SCAD .

Sterol A-ring plasticity in hedgehog protein cholesterolysis supports a primitive substrate selectivity mechanism.

Cholesterolysis of Hedgehog family proteins couples endoproteolysis to protein C-terminal sterylation. The transformation is self-catalyzed by HhC, a partially characterized enzymatic domain found in precursor forms of Hedgehog. Here we explore spatial ambiguity in sterol recognition by HhC, using a trio of derivatives where the sterol A-ring is contracted, fused, or distorted. Sterylation assays indicate that these geometric variants react as substrates with relative activity: cholesterol, 1.000 > A-ring contracted, 0.100 > A-ring fused, 0.020 > A-ring distorted, 0.005. Experimental results and computational sterol docking into the first HhC homology model suggest a partially unstructured binding site with substrate recognition governed in large part by hydrophobic interactions.

Host immunoglobulin G selectively identifies pathobionts in pediatric inflammatory bowel diseases.

BACKGROUND: Inflammatory bowel diseases (IBD) are a group of complex and multifactorial disorders with unknown etiology. Chronic intestinal inflammation develops against resident intestinal bacteria in genetically susceptible hosts. We hypothesized that host intestinal immunoglobulin (Ig) G can be used to identify bacteria involved in IBD pathogenesis. RESULTS: IgG-bound and -unbound microorganisms were collected from 32 pediatric terminal ileum aspirate washes during colonoscopy [non-IBD (n = 10), Crohn disease (n = 15), and ulcerative colitis (n = 7)], and composition was assessed using the Illumina MiSeq platform. In vitro analysis of invasive capacity was evaluated by fluorescence in situ hybridization and gentamicin invasion assay; immune activation was measured by qPCR. Despite considerable inter-individual variations, IgG binding favored specific and unique mucosa-associated species in pediatric IBD patients. Burkholderia cepacia, Flavonifractor plautii, and Rumminococcus sp. demonstrated increased IgG binding, while Pseudomonas ST29 demonstrated reduced IgG binding, in IBD. In vitro validation confirmed that B. cepacia, F. plautii, and Rumminococcus display invasive potential while Pseudomonas protogens did not. CONCLUSION: Using IgG as a marker of pathobionts in larger patient cohorts to identify microbes and elucidate their role in IBD pathogenesis will potentially underpin new strategies to facilitate development of novel, targeted diagnostic, and therapeutic approaches. Interestingly, this method can be used beyond the scope of this manuscript to evaluate altered gut pathobionts in a number of diseases associated with altered microbiota including arthritis, obesity, diabetes mellitus, alcoholic liver disease, cirrhosis, metabolic syndrome, and carcinomas.

Treatment-refractory vulvodynia from nutcracker syndrome: A case report.

BACKGROUND: Pelvic venous disorders are often undiagnosed due to the symptom variability and similarity to other disease presentations. 'Pelvic congestion syndrome' is a term often used as a diagnosis of exclusion, since there is currently no standardized diagnostic approach for pelvic venous disorders, which further delays treatment. CASE: A 25-year-old woman with treatment-refractory vulvodynia presented with symptoms that included left-sided vaginal wall pain, pruritis, dysmenorrhea, dyspareunia, muscle tension, and a chronic vaginal ulceration. Abnormal pelvic varices were discovered, and she was referred to vascular surgery for treatment of nutcracker syndrome causing ovarian vein reflux and abnormal engorgement of pelvic varices. CONCLUSION: Patients presenting with signs of pelvic venous insufficiency such as vaginal pruritis, irritation, pain, recurrent vaginitis, or chronic ulcerations should be examined for pelvic venous disorders.