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OBJECTIVE: The exposure-response relationship for manganese (Mn)-induced adverse nervous system effects is not well described. Symptoms and neuropsychological deficits associated with early manganism were previously reported for welders constructing bridge piers during 2003 to 2004. A reanalysis using improved exposure, work history information, and diverse exposure metrics is presented here. METHODS: Ten neuropsychological performance measures were examined, including working memory index (WMI), verbal intelligence quotient, design fluency, Stroop color word test, Rey-Osterrieth Complex Figure, and Auditory Consonant Trigram tests. Mn blood levels and air sampling data in the form of both personal and area samples were available. The exposure metrics used were cumulative exposure to Mn, body burden assuming simple first-order kinetics for Mn elimination, and cumulative burden (effective dose). Benchmark doses were calculated. RESULTS: Burden with a half-life of about 150 days was the best predictor of blood Mn. WMI performance declined by 3.6 (normal = 100, SD = 15) for each 1.0 mg/m3 x mo exposure (P = 0.02, one tailed). At the group mean exposure metric (burden; half-life = 275 days), WMI performance was at the lowest 17th percentile of normal, and at the maximum observed metric, performance was at the lowest 2.5 percentiles. Four other outcomes also exhibited statistically significant associations (verbal intelligence quotient, verbal comprehension index, design fluency, Stroop color word test); no dose-rate effect was observed for three of the five outcomes. CONCLUSIONS: A risk assessment performed for the five stronger effects, choosing various percentiles of normal performance to represent impairment, identified benchmark doses for a 2-year exposure leading to 5% excess impairment prevalence in the range of 0.03 to 0.15 mg/m3, or 30 to 150 microg/m3, total Mn in air, levels that are far below those permitted by current occupational standards. More than one-third of workers would be impaired after working 2 years at 0.2 mg/m3 Mn (the current threshold limit value). [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Cancer mortality and morbidity are described for the first time in all Korean workers exposed to ionizing radiation. METHODS:: Based on hospital admissions, Standardized Rate Ratios (SRR) and Standardized Mortality Ratios (SMR) were modeled with Poisson regression. RESULTS:: Cancer admissions during 2000 to 2005 were low compared with autoworkers with the exception of nuclear power workers (SRR = 1.13, 95% CI = 0.94-1.36). Thyroid cancer was statistically significantly elevated in women radiation workers in medical (SRR = 2.90, 95% CI = 1.05-7.94) and research institutions (SRR = 3.91, 95% CI = 1.36-11.0) and industry (SRR = 5.07, 95% CI = 1.56-15.6), and in all nuclear power workers (SRR = 2.59, 95% CI = 1.33-5.13), and there was a significant association with dose (ERR = 20.4 per Sv, 90% CI = -8 to 60, one-tailed P = 0.049). The 935 deaths revealed a healthy worker effect for all causes (SMR = 0.58, 95% CI = 0.54-0.62) and all-cancer (SMR = 0.73, 95% CI = 0.64-0.82). Lung cancer (SMR = 0.77, 95% CI = 0.55-1.05) and leukemia (SMR = 0.59, 95% CI = 0.28-1.06) mortalities were also less than expected. Compared with autoworkers, radiation workers displayed decreased all-cause mortality except for nuclear power workers (statistically not significant). CONCLUSIONS:: ERRs as high as 300 per Sv appear to be ruled-out in this population with regulated exposure to ionizing radiation while ERRs as high as 100 per Sv are not. [ABSTRACT FROM AUTHOR]

A very small proportion of all chemicals in commerce have occupational exposure limits (OELs) based on quantitative risk assessments which require estimates of exposure-response relationships (XRs). For only 18 of the 94 chemicals declared by NIOSH to be carcinogens were human XRs reported in or calculable from published reports. For the 18 carcinogens, 96 such XRs could be derived (corresponding to chemicals with multiple associated cancer end-points and/or multiple source studies). Twenty-four of 96 XR estimates came directly from reported statistical models (on continuous cumulative exposure), 45 were derived from summary study-population attributes, and 27 came from categorical analyses. Using the 96 XRs, OEL conferring one-per-thousand excess lifetime risk were calculated. OSHA's OEL, permissible exposure limits (PEL) were then compared to OEL derived from the 96 XRs. For 88 of the 96 calculated OELs (for which a corresponding PEL exists) all but 10 fell below the current PEL. Thirty-four OEL estimates were 10- to 100-fold below the PEL and 21 were greater than 100-fold below the PEL. This same pattern was observed using the different methods for deriving XRs. These findings can guide priorities in setting standards and the method is not limited to carcinogens.

Bacterial populations that originate from a single bacterium are not strictly clonal and often contain subgroups with distinct phenotypes 1 . Bacteria can generate heterogeneity through phase variation-a preprogrammed, reversible mechanism that alters gene expression levels across a population 1 . One well-studied type of phase variation involves enzyme-mediated inversion of specific regions of genomic DNA 2 . Frequently, these DNA inversions flip the orientation of promoters, turning transcription of adjacent coding regions on or off 2 . Through this mechanism, inversion can affect fitness, survival or group dynamics 3,4 . Here, we describe the development of PhaVa, a computational tool that identifies DNA inversions using long-read datasets. We also identify 372 'intragenic invertons', a novel class of DNA inversions found entirely within genes, in genomes of bacterial and archaeal isolates. Intragenic invertons allow a gene to encode two or more versions of a protein by flipping a DNA sequence within the coding region, thereby increasing coding capacity without increasing genome size. We validate ten intragenic invertons in the gut commensal Bacteroides thetaiotaomicron, and experimentally characterize an intragenic inverton in the thiamine biosynthesis gene thiC., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Development of respiratory tissue constructs is challenging due to the complex structure of native respiratory tissue and the unique biomechanical conditions induced by breathing. While studies have shown that the inclusion of biomechanical stimulus mimicking physiological conditions greatly benefits the development of engineered tissues, to our knowledge no studies investigating the influence of biomechanical stimulus on the development of respiratory tissue models produced through three-dimensional (3D) bioprinting have been reported. This paper presents a study on the utilization of a novel breath-mimicking ventilated incubator to impart biomechanical stimulus during the culture of 3D respiratory bioprinted constructs. Constructs were bioprinted using an alginate/collagen hydrogel containing human primary pulmonary fibroblasts with further seeding of human primary bronchial epithelial cells. Biomechanical stimulus was then applied via a novel ventilated incubator capable of mimicking the pressure and airflow conditions of multiple breathing conditions: standard incubation, shallow breathing, normal breathing, and heavy breathing, over a two-week time period. At time points between 1 and 14 days, constructs were characterized in terms of mechanical properties, cell proliferation, and morphology. The results illustrated that incubation conditions mimicking normal and heavy breathing led to greater and more continuous cell proliferation and further indicated a more physiologically relevant respiratory tissue model., (Copyright © 2024 by ASME.)

Background: Cancer and non-cancer associations have been observed with PFAS (perfluoroalkyl and polyfluoroalkyl) substances in the general population, in populations from locally contaminated environments and in exposed workers., Methods: A quantitative risk assessment on the PFAS substance perfluorooctanoic acid (PFOA) was conducted for six outcomes using two occupational mortality studies that reported sufficient data to estimate exposure-relationships in relation to serum PFOA levels. Excess lifetime mortality risks were calculated using a life table procedure that applies an exposure response to time-dependent PFOA serum levels for a surviving hypothetical population from ages 20 to 85. Both occupational and general population exposures were described as serum levels, and as air and drinking water concentrations., Results: The estimated occupational inhalation concentrations conferring the benchmark one-per-thousand lifetime risk were 0.21 µg/m 3 for chronic kidney disease, 1.0 µg/m 3 for kidney cancer and (from the two studies) 0.67 and 1.97 µg/m 3 for chronic liver disease. Specific excess lifetime risks estimated in the general population at current PFOA serum levels (~ 1 ng/mL) range 1.5-32 per 100 000 which corresponds to drinking water concentrations of less than 10 ppt., Conclusion: Over eight outcome risk estimates, the serum PFOA concentrations conferring 1/1000 occupational lifetime risk ranged 44 to 416 ng/mL corresponding to air concentrations ranging 0.21 to 1.99 µg/m 3 . The analyses provide a preliminary PFOA quantitative risk assessment for liver and kidney disease mortality which, together with reported assessments for several other end-points, would inform policy on PFAS., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Diesel exhaust in the latter half of the 20th century has been found to be a lung carcinogen. Conventional diesel emissions continue in the transportation, mining, construction, and farming industries. From the Diesel Exhaust in Miners Study, a public-use dataset was used to calculate the excess lifetime risk of lung cancer associated with diesel exposure (1947-1997). Excess rates of lung cancer mortality associated with respirable elemental carbon (REC) and possible other mining exposures (e.g., oil mists, explosives emissions) were investigated using Poisson regression methods. Lung cancer mortality declined with increasing employment duration while increasing with cumulative REC and non-diesel exposures, suggesting a strong worker survivor effect. Attenuation of the REC effect was observed with increasing cumulative exposure. After adjustment for employment duration, the excess rate ratio for lung cancer mortality was 0.67 (95% CI = 0.35-0.99) for a 10-year lagged exposure to 200 μg/m 3 REC, a typical below-ground exposure in the study mines. At exposures of 200, 10, and 1 μg/m 3 REC, the estimated excess lifetime risks, respectively, were 119, 43, and 8.7 per thousand. Analysis of an inception cohort hired after dieselization commenced produced smaller and less certain estimates of lifetime risk. From exposures to conventional diesel engine exhaust common in occupational groups in the past, the excess lifetime risk of lung cancer was more than 5%. Ambient REC exposures in the general population were estimated to confer lifetime risks of 0.14 to 14 per thousand, depending on assumptions made., (© 2023 Society for Risk Analysis.)

The loss of a companion animal results in millions of pet owners grieving annually. To date, little information has been synthesized on the grief response and coping mechanisms of bereaved pet owners. The aim of this review was to examine the relationship between pet loss and owner grief response. Major themes included: factors that influence the grief response, the disenfranchised nature surrounding pet loss, ambiguous pet loss and coping mechanisms used. Across the 48 studies included in this review, bereaved pet owners frequently reported feelings of embarrassment and loneliness following the loss of their pet. Types of coping mechanisms used by bereaved pet owners were identified and included: isolation, social support, continuing bonds, memorialization, religion, and relationships with other animals. Overall, this review was able to identify a consensus among the literature that bereaved pet owners are likely to experience disenfranchisement surrounding their loss. Based on the present findings, suggestions for future research include a focus on the effectiveness of coping mechanisms used by bereaved pet owners.

Efficient sampling strategies expedite behavioral data collection. While multiple studies have evaluated sampling strategies for core behaviors in cattle, few have focused on social interactions. To identify sampling strategies that accurately captured cattle social behaviors and brush use feedlot steers (n = 3 pens; 9 steers/pen) were observed from 8:00 to 17:00. Average bout duration (sec), total duration per day (sec), and bout frequency were recorded for allogrooming, bar licking, tongue rolling, and brush utilization. Frequency was recorded for headbutting and mounting. Data was extracted from continuous observation datasets using eight different sampling strategies and the results subsequently compared. Differences among sampling strategies were evaluated using a non-parametric One-Way ANOVA Kruskal-Wallis Test. Pearson correlation evaluated the strength of association between a specific sampling strategy and continuous observations. Bout duration for allogrooming (P > 0.65), bar licking (P > 0.60), tongue rolling (P > 0.99), brush use (P > 0.99), and mounting frequency (P > 0.70) did not differ from continuous observations. Tongue rolling (r2 > 0.95, P <0.0001) and brush use (r2 > 0.70, P < 0.0003) were best captured when cattle were observed from 08:00 to 14:00. When cattle were continuously observed from 08:00 to 14:00 or for 15 minutes every 30 minutes, allogrooming (P > 0.2) (frequency, duration), bar licking (P > 0.95) (frequency, duration), brush use (P > 0.1) (frequency, duration), heat butt (P > 0.30) (frequency), or tongue rolling (P > 0.30) (frequency, duration) did not differ from continuous observations. Observing cattle for 15 minutes every 30 minutes yielded the highest accuracy for all behavioral metrics and was considered the most effective strategy for comprehensively evaluating cattle social behavior (r2 > 75; P < 0.05). These results provide insight into accurate and efficient sampling strategies that expedite social behavior data collection in cattle and will facilitate efficient generation of new knowledge regarding cattle social behaviors., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2023 Lozada et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Many emerging adults have experienced increased financial distress and mental health problems during the COVID-19 pandemic, and isolation may have amplified the importance of close relationships (especially as parents' influence diminishes during this developmental stage). Using the ABC-X Model to frame our model, we tested whether financial distress (C) mediates the associations between COVID-19 impact (A) and anxiety and depressive symptoms (X), and whether or not romantic relationship quality (B) moderates these indirect associations. Our sample comprised of 1950 U.S. emerging adults in a romantic relationship. Mediation and first-stage moderated mediation were tested using structural equation modeling. Financial distress partially mediated the association between COVID-19 impact and anxiety symptoms and fully mediated the association between COVID-19 impact and depressive symptoms. Strong evidence of moderated mediation was found but in the opposite direction expected: the indirect associations of COVID-19 impact with anxiety and depressive symptoms (through financial distress) were stronger for those in high-quality romantic relationships. The findings may inform policy and practice aimed at optimizing the mental health of emerging adults, especially in light of the ongoing COVID-19 pandemic: specifically, alleviating financial distress may improve the mental health of emerging adults, while focusing on the quality of their romantic relationships may not.

The Continuous NHANES Survey provides detailed health and environmental chemical burden information on the U.S. population. As of 2012, there were data for 72,000 participants. Based on single biomarker determinations, cumulative burdens were estimated. Because age distributions would differ comparing ambient environmental and occupational exposures, a procedure to distinguish ambient from likely occupational exposures was applied. Associations are reported for osteoporosis and kidney disease-related outcomes with cadmium, lead, and other metals. Cumulative cadmium burden (from blood cadmium, ambient and occupational) was a strong predictor of bone fracture risk and ambient tungsten also had a positive association. Cumulative lead (ambient and occupational) had a negative ("protective") association with fractures as did mercury (occupational). Bone mineral density was statistically significant and similarly predicted by metal exposures. Kidney disease was significantly associated with cumulative lead burdens from both the estimated ambient and occupational sources and with ambient blood cadmium but was most strongly associated with cumulative occupational uranium burden. Systolic blood pressure statistically significantly increased with cumulative ambient and occupational lead (blood) burden and with ambient cadmium and cobalt. Diastolic blood pressure was significantly associated with several cadmium and cobalt metrics along with ambient and occupational cumulative burdens for lead. For environmental substances with burden half-lives measured in years, NHANES offers opportunities for hypothesis generation and confirmation.

Background: COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms. 1 , SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms. 5 ., Methods: We analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms., Findings: Fecal SARS-CoV-2 RNA is detected in 49.2% [95% confidence interval, 38.2%-60.3%] of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% [8.5%-18.4%] of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% [2.0%-7.3%] shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA., Conclusions: The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19., Funding: This research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142., Competing Interests: The authors declare no competing interests., (© 2022 Elsevier Inc.)

Competing Interests: The author declares no conflicts of interest.

Castration is a painful procedure routinely performed on piglets. Specific periods relative to castration and time sampling rules are used widely to quantify deviations in piglet's behavior associated with castration rather than assessing behavior for the entire trial period. However, very limited work has evaluated time sampling recording rules to quantify behavioral changes to piglets undergoing castration. Therefore, the objective of this study was to validate the accuracy of six continuous time sampling periods (5, 10, 15, 20, 30, and 45 min), to quantify piglet behavior post-castration when compared with a full 60-min observation period. Sixteen Yorkshire-Landrace x Duroc piglets were surgically castrated. Data were collected using continuous observation (recording rule) of each individual male piglet per litter for 60-min post-castration. The 60-min continuous behavioral data set was then subdivided into six data subsets for each defined continuous time sampling period (5, 10, 15, 20, 30, and 45 min). Data from each continuous time sampling period and the full period data were analyzed using both a generalized linear mixed model and linear regression analysis. For the generalized linear mixed model, 30- and 45-min continuous time sampling periods were not different (P > 0.05) when compared with the full observation period data for all behaviors. For the linear regression analysis, affiliative interaction, sitting, walking, huddled up, prostrated, scratching, spasms, and trembling behaviors met the pairwise comparison accuracy criteria: [1) the coefficient of determination (R2) was > 0.90, 2) the intercept did not differ from 0 (P > 0.05), and 3) the slope did not differ from 1 (P > 0.05)] at the 45-min continuous time sampling period compared to full observation period. Results from this study suggest that a 45-min continuous time sampling period would be necessary to accurately investigate piglet behavior during the acute pain sensitivity time post-castration when considering both maintenance and pain-associated behaviors., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Quantitative sensory testing (QST) is used to evaluate the function of the somatosensory system in dogs by assessing the response to applied mechanical and thermal stimuli. QST is used to determine normal dogs' sensory thresholds and evaluate alterations in peripheral and central sensory pathways caused by various disease states, including osteoarthritis, spinal cord injury, and cranial cruciate ligament rupture. Mechanical sensory thresholds are measured by electronic von Frey anesthesiometers and pressure algometers. They are determined as the force at which the dog exhibits a response indicating conscious stimulus perception. Hot thermal sensory thresholds are the latency to respond to a fixed or ramped temperature stimulus applied by a contact thermode. Following a consistent protocol for performing QST and paying attention to details of the testing environment, procedure, and individual study subjects are critical for obtaining accurate QST results for dogs. Protocols for the standardized collection of QST data in dogs have not been described in detail. QST should be performed in a quiet, distraction-free environment that is comfortable for the dog, the QST operator, and the handler. Ensuring that the dog is calm, relaxed, and properly positioned for each measurement helps produce reliable, consistent responses to the stimuli and makes the testing process more manageable. The QST operator and handler should be familiar and comfortable with handling dogs and interpreting dogs' behavioral responses to potentially painful stimuli to determine the endpoint of testing, reduce stress, and maintain safety during the testing process.

Background: Elevated bladder cancer incidence has been reported in a cohort of 1875 workers manufacturing chemicals used in the rubber industry and employed any time during 1946-2006. o-Toluidine (OT), an aromatic amine, was the prime suspect agent. Using the available environmental data and process characterization, previous investigators assigned ranks to volatile chemical air concentrations across time in departments and jobs, reflecting probabilities of exposure and use of personal protective equipment for airborne and dermal exposures. Aniline, another aromatic amine, was present at comparable concentrations and is known to be an animal carcinogen but produced lower levels in post-shift urine and of hemoglobin adducts than OT in a group of workers., Methods: A quantitative risk assessment was performed based on this same population. In this study, cumulative OT exposures were estimated (a) based on previously assigned ranks of exposure intensity and reported actual exposures in jobs with the highest assigned rank, and (b) directly from the historical environmental sampling for OT. Models of bladder cancer incidence were evaluated taking into account possible healthy worker survivor effects., Results: Under various assumptions regarding workforce turnover, the excess lifetime risk of bladder cancer from OT exposure at 1 ppb was estimated to be in the range 1-7 per thousand., Conclusions: The current ACGIH TLV and OSHA standards for OT are 2 and 5 ppm, respectively, 1000-fold higher than the exposure estimated here for 1-7 per thousand excess lifetime risk., (© 2021 Wiley Periodicals LLC.)

Acrylamide (ACM) is a high-volume industrial chemical with diverse uses in manufacturing, construction and laboratory research. ACM is a well-established neurotoxic agent causing peripheral neuropathy with impairment in the arms and legs of exposed workers, most thoroughly studied in Swedish tunnel workers exposed to ACM grouting. A quantitative risk assessment was performed to assess ACM risk to workers. Using data from a published paper investigating peripheral neuropathies in Chinese chemical workers, estimates of exposure response for vibration perception threshold and nerve conduction velocities were calculated, based on hemoglobin adducts and air concentrations as exposure metrics. The benchmark dose procedure was applied in order to calculate excess risks of impairment, defined as adverse performance exceeding the 95 th percentile in unexposed populations, at various concentrations of airborne ACM exposure. Under the assumptions in this risk assessment, after three years of inhalation exposure at 0.3 mg/m 3 , the excess attributable impairment manifest in vibration perception and nerve conduction velocity is estimated to occur in 1-2% of workers. For 10 years at 0.3 mg/m 3 ACM inhalation (equivalent to 3 years at 1.0 mg/m 3 ) the excess prevalence of impairment would be 2-14% of workers, assuming the effect continues to accrue linearly in time. Using published data, the risks of impairment from peripheral neuropathy attributable to exclusively airborne ACM exposure can be predicted for exposure periods less than 10 years. The risks associated with dermal and airborne ACM exposures can be estimated by characterizing working process environments using ACM Hb-adduct levels and possibly monitored with urinary biomarkers., (Published by Elsevier B.V.)

Background: Toluene diisocyanate (TDI) is a highly reactive chemical that causes sensitization and has also been associated with increased lung cancer. A risk assessment was conducted based on occupational epidemiologic estimates for several health outcomes., Methods: Exposure and outcome details were extracted from published studies and a NIOSH Health Hazard Evaluation for new onset asthma, pulmonary function measurements, symptom prevalence, and mortality from lung cancer and respiratory disease. Summary exposure-response estimates were calculated taking into account relative precision and possible survivor selection effects. Attributable incidence of sensitization was estimated as were annual proportional losses of pulmonary function. Excess lifetime risks and benchmark doses were calculated., Results: Respiratory outcomes exhibited strong survivor bias. Asthma/sensitization exposure response decreased with increasing facility-average TDI air concentration as did TDI-associated pulmonary impairment. In a mortality cohort where mean employment duration was less than 1 year, survivor bias pre-empted estimation of lung cancer and respiratory disease exposure response., Conclusion: Controlling for survivor bias and assuming a linear dose-response with facility-average TDI concentrations, excess lifetime risks exceeding one per thousand occurred at about 2 ppt TDI for sensitization and respiratory impairment. Under alternate assumptions regarding stationary and cumulative effects, one per thousand excess risks were estimated at TDI concentrations of 10 - 30 ppt. The unexplained reported excess mortality from lung cancer and other lung diseases, if attributable to TDI or associated emissions, could represent a lifetime risk comparable to that of sensitization., Competing Interests: The author declares no conflicts of interest.

The objective of this study was to report that lysosome extracted from egg white could be used as a drug through oral administration for treating diseases by using pH sensitive alginate oligosaccharides. Lysosome-alginate oligosaccharides composite were formulated for oral administration of lysosomes. The dissolution test confirmed the availability of the oral dosage form. When lysosome were used as an independent drug, the activity of protein was lost due to influence of low pH. Its antibacterial activity was also remarkably reduced. However, when lysosome-alginate oligosaccharides composite form was used, antimicrobial activity of lysozyme was maintained. At low pH, a gel-like matrix was formed by alginate oligosaccharides to protect the lysosome. When the pH was increased, alginate oligosaccharides were dissolved and the lysosome was released. SDS-polyacrylamide gel electrophoresis analysis of released lysosomes revealed that alginate oligosaccharide could effectively protect the lysosome from degradation or hydrolysis under acidic conditions for at least 2 h. The results of this study are important for application of lysosomes as therapeutic agents, and also it was confirmed that alginate oligosaccharides have potential as direct delivery system for the oral application of protein derived therapies.

The yeast vacuole is functionally corresponding to vacuoles in eukaryote cells, it consists of a fusion protein that assists in the fusion of vacuoles and plays an important role in many processes. In addition, chemicals such as NH 4 Cl can reduce the size of vacuoles but as a side effect that also inhibits vacuoles making them inactive. In this study, to develop pre-treatments for extending the life of cut flowers, we constructed recombinant yeast using the fusion protein YPT7 and confirmed the activity of down-sized vacuoles. All the vacuoles of the recombinant yeast except vacuoles from recombinant yeast (MBTL-MYH-3) were found to be small vacuoles than mock (MBTL-MYH-0) and YPT7 overexpression model (MBTL-MYH-1). To confirm their activity, we conducted a test for antimicrobial activity. The results showed the other vacuoles of recombinant yeast had lower antimicrobial activity than the mock control, most of them showed about 60 % to 80 % of the antimicrobial activity. However, MBTL-MYH-3, whose vacuole did not change its size, showed antimicrobial activity lower than 40 %. Therefore, the cut flowers are better able to absorb smaller vacuoles after using the fusion protein YPT7. We expect that absorbing vacuoles more effective to senescence of cut flower than vacuolar enzymes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

(1) Background: An important aspect of dog ownership is providing veterinary care. However, features of dog ownership differ across demographic groups and these may influence veterinary client decision making and behavior. The purpose of the present study was to elucidate relationships between American dog owner characteristics and willingness to seek veterinary care. (2) Methods: A total of 858 dog owners completed an online questionnaire asking participants to rate their level of likelihood to seek veterinary care for different medical conditions, answer supplemental questions about their previous veterinary barriers, and indicate barriers that prevent them from seeking veterinary care. (3) Results: Dog owners did not differ by demographics in their willingness to seek veterinary care. However, dog owner demographic groups varied in their relationship with their dog(s), previous behaviors accessing veterinary care, and barriers that make seeking veterinary care challenging. (4) Conclusions: Education, outreach and community-based veterinary medicine efforts should allocate resources to underserved communities identified within the context that they are affected by barriers to obtaining veterinary care for their dog(s).

A real-time dPCR system was developed to improve the sensitivity, specificity and quantification accuracy of end point dPCR. We compared three technologies - real-time qPCR, end point dPCR and real-time dPCR - in the context of SARS-CoV-2. Some improvement in limit of detection was obtained with end point dPCR compared with real-time qPCR, and the limit of detection was further improved with the newly developed real-time dPCR technology through removal of false-positive signals. Real-time dPCR showed increased linear dynamic range compared with end point dPCR based on quantitation from amplification curves. Real-time dPCR can improve the performance of TaqMan assays beyond real-time qPCR and end point dPCR with better sensitivity and specificity, absolute quantification and a wider linear range of detection.

The study of senescence preservative on cut flowers helps boost the commercial value of flowers. Senescence in cut flower is associated with an increase of ethylene production, and is significantly influenced by ethylene pathway. This study was conducted to investigate whether S-adenosyl-L-methionine (SAM) and aminocyclopropane-1-carboxylic acid (ACC) involved in the ethylene synthesis process are correlated with the lysosome. The alterations of lysosome which was treated with the ethylene precursors ACC and SAM in HeLa cell using the confocal laser scanning microscope were investigated. According to the experimental results, the activity of lysosomes increased concentration dependently by ACC treatment, however, no change was observed by SAM treatment. In addition, Liquid chromatography-mass spectrometry (LC/MS) analysis was performed to confirm the effect of lysosomal enzyme (LE) extracted from egg white on ACC reduction, but no change was observed. On the contrary, to confirm the effect of ACC on lysosomes, lysosomes were extracted from HeLa cells treated with 5 mM ACC and confirmed by FE-SEM. The results showed that the size of lysosomes treated with ACC is larger than that of the control, which was treated with distilled water. The lysosomes in the control group were distributed in various ranges from 0 to 800 nm, but those treated with 5 mM ACC were in the range of 400 nm to 800 nm or more. Therefore, lysosomes had no effect on ACC, the precursor of ethylene, the aging hormone of cut flowers, however, ACC had effect on lysosomes.

Uncertainty in model predictions of exposure response at low exposures is a problem for risk assessment. A particular interest is the internal concentration of an agent in biological systems as a function of external exposure concentrations. Physiologically based pharmacokinetic (PBPK) models permit estimation of internal exposure concentrations in target tissues but most assume that model parameters are either fixed or instantaneously dose-dependent. Taking into account response times for biological regulatory mechanisms introduces new dynamic behaviors that have implications for low-dose exposure response in chronic exposure. A simple one-compartment simulation model is described in which internal concentrations summed over time exhibit significant nonlinearity and nonmonotonicity in relation to external concentrations due to delayed up- or downregulation of a metabolic pathway. These behaviors could be the mechanistic basis for homeostasis and for some apparent hormetic effects., (© 2020 Society for Risk Analysis.)

2-Nonenal is a long-chain aliphatic aldehyde containing nine carbons and an unsaturated bond. 2-Nonenal is the primary cause of odor associated with aging, with an unpleasant greasy and grassy odor. Lysosome, mitochondria, and peroxisome are significant organelles in eukaryotic cells that contain various hydrolases that degrade biomolecules. Proteins in mitochondria and peroxisome also contain aldehyde dehydrogenase. We performed trans-2-nonenal treatment using lysosomal-related enzymes extracted from hen egg white (HEW). As trans-2-nonenal is more structurally stable than cis-2-nonenal, it was selected as the target aldehyde. HEW contains various biologically active proteins and materials such as albumin, ovotransferrin, lysosome, peroxisome, and mitochondria. Here, complementary experiments were conducted to evaluate the role of lysosomal-related enzymes in the treatment of trans-2-nonenal. The activity of lysosomal-related enzymes was confirmed via antimicrobial test against E. coli. HPLC analysis was used to determine the reduction of trans-2-nonenal. The trans-2-nonenal treatment depended on the reaction time and enzyme concentration. Materials considered as an intermediate from trans-2-nonenal treatment were detected by GC/MS spectrometer. Under acidic conditions (pH 6), lysosomal-related enzymes were the most efficient in the treatment of trans-2-nonenal. Furthermore, based on differential pH testing, we found the conditions under which all the 50 ppm trans-2-nonenal was removed. Therefore, our results suggest that the lysosomal-related enzymes reduced trans-2-nonenal, suggesting clinical application as anti-aging deodorants.

Background: Previous analyses of mortality were conducted in a large cohort of ethylene oxide (EtO) exposed workers employed at 13 sterilization facilities throughout the U.S. and followed from the start of operation through 1998. Statistically significant elevated mortality was reported from hematopoietic cancer in men and breast cancer in women compared to the general population. Possible healthy worker survivor bias was not addressed., Methods: To examine survivor bias in this cohort, employment termination was analyzed with statistical models stratified on sex and race that included age, employment duration, and cumulative EtO exposure. To reduce survivor bias employment duration was included in Poisson regression model specifications for estimating standardized mortality ratios for several cancer outcomes., Results: Strong statistically significant effects of unlagged cumulative EtO exposure were observed on rate of employment termination, indicating potential healthy worker survivor effect bias. Adjustment for employment duration in analyses of mortality resulted in statistically significant and stronger associations between cumulative EtO exposure and lung cancer, female breast cancer and hematopoietic cancer. There was a striking reduction in nonmalignant respiratory disease mortality risk with increasing employment duration with a further (nonsignificant) reduction with cumulative EtO, suggesting that EtO itself is driving termination of workers with respiratory morbidity even though the average EtO exposures in this population were generally far below odor and acute irritancy thresholds., Conclusions: Important survivor bias was present in this EtO cohort and may be present in many occupational settings involving irritant exposures., (© Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

The objective of this study was to find a practical means of reducing pain associated with surgical castration by evaluating the effects of oral meloxicam and topical lidocaine, separately and in combination, on behavioral indicators of pain in piglets. Two hundred thirty-five piglets were surgically castrated between three and seven days of age. Immediately following castration, piglets received one of four treatments: (1) No pain mitigation (C; control; n = 58); (2) NSAID only (M; meloxicam; n = 59); (3) Topical anesthetic (L; lidocaine spray; n = 60); or (4) NSAID and topical anesthetic (X; meloxicam and lidocaine spray; n = 59). Behaviors were recorded by direct observation of individual piglets using five-minute scan samples over a five-hour period, for three days post-castration. Results of the experiment demonstrate the administration of oral meloxicam and topical lidocaine spray at the time of castration under the current methods did not mitigate pain associated with the procedure ( P  = 0.09; C: 2.1 ± 0.1, L: 2.4 ± 0.1, M: 2.1 ± 0.1 and X: 2.1 ± 0.1).

Housing systems and environmental features can influence beef cattle welfare. To date, little information has been synthesized on this topic. The aim of this scoping review was to examine the relationship between housing and welfare status, so that beef cattle producers and animal scientists can make informed decisions regarding how their housing choices could impact beef cattle welfare. Housing features were categorized by floor type, space allowance and shade availability, as well as the inclusion of enrichment devices or ventilation features. Evaluation of space allowances across feedlot environments determined behavioral and production benefits when cattle were housed between 2.5 m 2 to 3.0 m 2 per animal. Over 19 different flooring types were investigated and across flooring types; straw flooring was viewed most favorably from a behavioral, production and hygiene standpoint. Veal calves experience enhanced welfare (e.g., improved behavioral, physiological, and performance metrics) when group housed. There is evidence that the implementation of progressive housing modifications (e.g., shade, environmental enrichment) could promote the behavioral welfare of feedlot cattle. This review presents the advantages and disadvantages of specific housing features on the welfare of beef cattle.

Background: Metalworking fluids (MWFs) are mixtures with inhalation exposures as mists, dusts, and vapors, and dermal exposure in the dispersed and bulk liquid phase. A quantitative risk assessment was performed for exposure to MWF and respiratory disease., Methods: Risks associated with MWF were derived from published studies and NIOSH Health Hazard Evaluations , and lifetime risks were calculated. The outcomes analyzed included adult onset asthma, hypersensitivity pneumonitis, pulmonary function impairment, and reported symptoms. Incidence rates were compiled or estimated, and annual proportional loss of respiratory capacity was derived from cross-sectional assessments., Results: A strong healthy worker survivor effect was present. New-onset asthma and hypersensitivity pneumonitis, at 0.1 mg/m 3 MWF under continuous outbreak conditions, had a lifetime risk of 45%; if the associated microbiological conditions occur with only 5% prevalence, then the lifetime risk would be about 3%. At 0.1 mg/m 3 , the estimate of excess lifetime risk of attributable pulmonary impairment was 0.25%, which may have been underestimated by a factor of 5 or more by a strong healthy worker survivor effect. The symptom prevalence associated with respiratory impairment at 0.1 mg/m 3 MWF was estimated to be 5% (published studies) and 21% (Health Hazard Evaluations)., Conclusion: Significant risks of impairment and chronic disease occurred at 0.1 mg/m 3 for MWFs in use mostly before 2000. Evolving MWFs contain new ingredients with uncharacterized long-term hazards.

This study provided a system for bacteria detection based on a lysosome-like-vacuole response in the yeast Saccharomyces cerevisiae. Vacuoles are factors known to activate the immune system in the presence of foreign substances. Here, Shigella sonnei and Shigella flexneri were exposed to yeast to analyze the alteration of vacuolar enzymes. The ability to detect the bacteria was evaluated by confocal microscopy after exposing and staining vacuoles with LysoTracker. Results showed that the treatment of yeast with these bacteria increased the number of red vacuole-like organelles surrounding yeast nuclei. Thus, vacuole alteration can be used as a biomarker for bacteria detection. Next, the expression of vacuolar enzymes under the influence of bacteria was examined using two-dimensional gel electrophoresis (2-DE) method for screening specific biomarkers for each Shigella strain. Finally, the recombinant yeasts that contained biomarkers fused to different fluorescent proteins confirmed the ability of yeast to detect these two Shigella strains at concentrations ranging from 10 to 100 CFU/mL., (Copyright © 2018 Elsevier B.V. All rights reserved.)