Strain Differences Research Articles

SEX AND STRAIN DIFFERENCES BETWEEN DISC1-L100P AND C57BL/6 MICE IN PASSIVE AVOIDANCE CONDITIONING DEFINATION

Sex and strain differences in the passive avoidance learning and extinction in male and female of DISC1-L100P mice and wild-type control mice were investigated. It was shown that male and female mice of both strains were well trained in the conditioned response of passive avoidance, but differed in fear memory extinction, the ability to form a new memory trace about the safety of the previously punished dark compartment of apparatus in the procedure of repeated testing. There was a deficit of fear memory extinction in females of DISC1-L100P and C57BL/6 mice compared to males. At the same time, interstrain differences in the dynamics of passive avoidance extinction in female mice of these strains were revealed. Results also showed that DISC1-L100P males differed from C57BL/6 in terms of the time to achieve complete extinction of this reaction.

Effect of spermidine on endothelial function in Systemic Lupus Erythematosus (SLE)

Impaired endothelial function has been shown in SLE patients and lupus-prone mice. Emerging evidence supports impaired mitochondrial dynamics and mitophagy contribute to SLE and endothelial dysfunction. Spermidine is a natural polyamine that stimulates mitophagy by activating the PINK1-Parkin pathway and can improve endothelial function. However, the effect of spermidine on mitophagy and vascular function in SLE has not been explored. To address this gap, 9-week-old female lupus-prone (MRL/lpr) and healthy control (MRL/MpJ) mice were randomly assigned into one of two groups, spermidine treatment (Lpr T and MpJ T) or control (Lpr C and MpJ C). Treated mice received spermidine (3mM) via drinking water for 8 weeks. After 8 weeks of treatment, endothelium-dependent vasorelaxation to acetylcholine (ACh) and endothelium-independent vasorelaxation to sodium nitroprusside (SNP) were measured in thoracic aortas using a wire myograph. Maximal responses to ACh were significantly impaired in Lpr C (67.1 ± 8.7, n = 11) compared to Mp C (90.3 ± 3.1, n = 13) (p = 0.01). Spermidine improved endothelial function in thoracic aorta from Lpr T (90.3 ± 2.8, n = 13) compared to Lpr C (p = 0.03). Maximal responses to SNP were not significantly different across the groups. Thoracic and abdominal aortas were used for measurements of protein content (n = 3-4/group) and gene expression (n = 4/group), respectively. There were strain differences in the mRNA expression of endothelial nitric oxide synthase ( Nos3) between Lpr C (0.65 ± 0.14) and MpJ C (1.00 ± 0.16) (p = 0008). In MpJ mice, Nos3 mRNA expression was significantly higher in the aorta from the MpJ T (1.47 ± 0.39) compared to MpJ C (p = 0.04). No significant differences were found in the Nos3 expression between Lpr groups. Vascular cell adhesion molecule 1 (Vcam1) is an indicator of inflammation and is associated with atherosclerosis susceptibility. Protein content of Vcam1 was significantly lower in Lpr T (3.73 ± 0.61) compared to Lpr C (8.49 ± 2.58) (p = 0.04) and gene expression of Vcam1 was also lower in Lpr T compared to Lpr C, suggesting spermidine decreases the inflammatory responses in vessels from SLE mice. Protein content of Parkin was measured as a marker of mitophagy. Parkin was significantly lower in Lpr C (0.38 ± 0.61) compared to MpJ C (1.00 ± 0.09) (p = 0.004), suggesting lower mitophagy in aorta from SLE mice. Parkin content in Lpr T was similar to MpJ C. Collectively, these results demonstrate the beneficial effects of spermidine treatment on endothelial function in SLE mice and suggest inflammation and altered mitophagy contribute to endothelial dysfunction in SLE. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

PO-01-095 REGIONAL DIFFERENCES IN ATRIAL FIBER STRAINS IN HEART FAILURE PATIENTS WITH AND WITHOUT ATRIAL FIBRILLATION

Left atrial (LA) strain is inhibited by atrial fibrosis, which is a hallmark of atrial fibrillation (AF). Retrospective gated computed tomography (CT) imaging with feature tracking (FT) can measure three-dimensional (3D) local LA strain. Atrial myocardial fiber directions may play an important role in preferred deformation, and therefore atrial fiber strains should be considered. Using the average endocardial fiber architecture from seven hearts imaged ex vivo with high resolution diffusion-tensor magnetic resonance imaging (DT-MRI), the endocardial fiber strain can be measured. To investigate regional and global differences in atrial endocardial fiber strains between heart failure (HF) patients with and without AF. 30 HF patients underwent 10-frame gated CT imaging, and FT was used to measure local endocardial fiber strain (Fig. A). The LA body was classified into five regions using Universal Atrial Coordinates (Fig. B). Global and regional strains were reported as the mean strain over the entire LA body surface and within each region, respectively. The fiber strain range over the cardiac cycle was used to stratify between HF patients with and without AF. The left ventricular ejection fraction (LVEF) and left atrial ejection fraction (LAEF) were calculated from the gated CT images. HF patients with AF had smaller global fiber strain ranges than those without AF (5.9 ± 3.7 % vs 14.2 ± 8.9 %, p = 0.011) (Fig. C). All regions had higher strain ranges in HF patients without AF and the anterior wall exhibited the most significant difference between groups (7.8 ± 4.1 vs 17.9 ± 10.6, p = 0.009). ROC analysis using global strain range to stratify between patient groups gave an AUC of 0.853 (Fig. D). The anterior wall was the region with the highest AUC of 0.842. LVEF was similar between patient groups (p=0.682), however LAEF differed (p=0.002) (Fig. E). Patients with AF had decreased fiber strain ranges globally and regionally compared to those without AF. Strain range in the anterior wall most significantly decreased in the presence of AF, which may suggest a regionally higher fibrosis burden. The LVEF was similar between HF patients with and without AF, however the LAEF differed, which suggests strain differences were driven by LA dysfunction.

Flexural creep of multi-wall carbon nanotube reinforced cement based composites under high stress level

Different concentrations (0–0.2 wt.%) of multiwall carbon nanotubes (MWCNT) was used to improve the mechanical properties of cementitious composites. The first part of the work showed that adding 0.05 wt.% of MWCNT produced a maximum reinforcement in terms of flexural and compressive strength. The second, the role of MWCNT on mechanical strength improvement was investigated. MWCNTs can absorb water to weaken the cement hydration at the beginning, and then, release water to promote the hydration of cement. The third part focused on using a home-made four-point bending testing device to study the flexural creep behavior under high stress levels (70, 80 and 90% of the flexural strength) and the results are discussed in terms of creep strain and Poisson ratio difference. The data obtained were also compared with the empirical creep models and the creep coefficients obtained were agreement with that from the AASHTO model. Finally, a regression analysis was used to fit the creep compliance of MWCNTs reinforced cementitious composites for the range of conditions studied. The results showed that the creep compliance can be fitted by a power-law for a stress level below 0.85, while a linear function was obtained above.

Neuroinvasive EV-D68 infection in cerebral organoids mimics human pathology

Abstract Emerging viruses with the capacity to cause neurological disease remain a global health threat. One such virus, Enterovirus-D68 (EV-D68), has recently received attention due to an associative rise in cases of a polio-like paralytic disease called acute flaccid myelitis (AFM) in some children. Although EV-D68 was identified in the 1960s (prototypic strain Fermon), circulating neuroinvasive EV-D68 strains have evolved to infect cells of the central nervous system. AFM remains a rare infection outcome, suggesting that host immune responses may play a role in limiting disease. Studies of such immune responses as well as tools to examine these responses remain limited. To this end, we seek to understand how neuroinvasive and non-neuroinvasive EV-D68 differentially modulate immune responses using both neuronal cultures and cerebral organoids. We infected neuroblastoma cells (SH-SY5Y cells) with Fermon and neuroinvasive EV-D68 and found that both viruses were able to replicate in these cells, which is different from what is observed during human disease. Thus, to better dissect strain differences and model human disease, we generated cerebral organoids and infected with our EV-D68 strains. We now found that cerebral organoids were more permissive to neuroinvasive EV-D68 infection compared to Fermon. Further, we found that neuroinvasive EV-D68 infection led to a global increase in the interferon-stimulated gene IFIT1 activation, whereas Fermon infection led to modest IFIT1 activation in bystander cells. These data suggest that immune responses can better control Fermon infection compared to neuroinvasive EV-D68, and also highlight the utility of using cerebral organoids to examine neurotropic virus regulation of immune responses. Supported by grants from the Burroughs Wellcome Fund and the Office of the University of the Provost

Immunopathogenesis of Campylobacter jejuniinfection in a small animal model

Abstract We set out to develop and characterize a small animal model of Campylobacter jejuni(CJ) infection that recapitulates human campylobacteriosis. Adult C57BL/6J mice are rendered susceptible to colonization and disease by pre-treatment with a zinc deficient diet and a broad-spectrum antibiotic cocktail. We have established this model with four strains with diverse capsular serotypes and flagellar groups, two key virulence factors for CJ pathogenesis. We measured colonization, weight loss, diarrhea, fecal inflammatory markers, and cytokine production by mesenteric lymphocytes and splenocytes. Diarrhea containing visible mucous and/or blood and degree of weight loss vary in severity depending on the strain and dose. Interestingly, we identified an inverse relationship between inoculum dose and levels of fecal inflammatory markers, with lower inoculum doses inducing significantly higher inflammation. We also observed production of IFNγ and IL-17 at day 9 post infection and despite no decrease in CJ colonization, IFNγ and IL-17 levels decreased by day 21 with a subsequent increase in IL-10 production. We also observed higher levels of IFNγ and IL-17 in mice challenged with strain CG8486 relative to those challenged with strain 81–176 pointing to potential strain differences. These differences observed were more striking in mesenteric lymphocytes versus splenocytes, indicating that local cellular responses differed from systemic responses. We have developed a model of inflammatory diarrhea in adult mice that exhibits hallmarks of CJ infection and further identified significant shifts in cytokine expression associated with the duration of infection, bacterial strain utilized, and therapeutic treatment. Research reported in this presentation is supported by Navy work unit number: 6000.RAD1.DA3.A0308 and CARB-X. CARB-X’s funding for this project is sponsored by the Cooperative Agreement Number IDSEP160030 from ASPR/BARDA and by awards from Wellcome Trust, the UK Global Antimicrobial Resistance Innovation Fund (GAMRIF) funded by the UK Government Department of Health and Social Care (DHSC) and the Bill & Melinda Gates Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of CARB-X or any of its funders. Disclaimers: The views expressed in this work are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government. F. Poly is an employee of the U.S. Government. This work was prepared as part of official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines a U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person’s official duties.The animal study protocol was reviewed and approved by the Naval Medical Research Center IACUC in compliance with all applicable Federal regulations governing the protection of animals in research.

Strain differences in the drug transport capacity of intestinal glucose transporters in Sprague–Dawley versus Wistar rats, C57BL/6J versus Kunming mice

Designing oral drug delivery systems using intestinal glucose transporters (IGTs) may be one of the strategies for improving oral bioavailability of drugs. However, little is known about the biological factors affecting the drug transport capacity of IGTs. Gastrodin is a sedative drug with a structure very similar to glucose. It is a highly water-soluble phenolic glucoside. It can hardly enter the intestine through simple diffusion but exhibits good oral bioavailability of over 80%. We confirmed that gastrodin is absorbed via the intestinal glucose transport pathway. It has the highest oral bioavailability among the reported glycosides’ active ingredients through this pathway. Thus, gastrodin is the most selective drug substrate of IGTs and can be used to evaluate the drug transport capacity of IGTs. Obviously, strain is one of the main biological factors affecting drug absorption. This study firstly compared the drug transport capacity of IGTs between SD rats and Wistar rats and between C57 mice and KM mice by pharmacokinetic experiments and single-pass intestinal perfusion experiments of gastrodin. Then, the sodium-dependent glucose transporter type 1 (SGLT1) and sodium-independent glucose transporters type 2 (GLUT2) in the duodenum, jejunum, ileum and colon of these animals were quantified using RT-qPCR and Western blot. The results showed that the oral bioavailability of gastrodin in Wistar rats was significantly higher than in SD rats and significantly higher in KM mice than in C57 mice. Gastrodin absorption significantly differed among different intestinal segments in SD rats, C57 mice and KM mice, except Wistar rats. RT-qPCR and Western blot demonstrated that the intestinal expression distribution of SGLT1 and GLUT2 in SD rats and C57 mice was duodenum ≈ jejunum > ileum > colon. SGLT1 expression did not differ among different intestinal segments in KM mice, whereas the intestinal expression distribution of GLUT2 was duodenum ≈ jejunum ≈ ileum > colon. However, the expression of SGLT1 and GLUT2 did not differ among different intestinal segments in Wistar rats. It was reported that the intestinal expression distribution of SGLT1 and GLUT2 in humans is duodenum > jejunum > ileum > colon. Hence, the intestinal expression distribution of SGLT1 and GLUT2 of SD rats and C57 mice was more similar to that in humans. In conclusion, the drug transport capacity of IGTs differs in different strains of rats and mice. SD rats and C57 mice are more suitable for evaluating the pharmacokinetics of glycosides’ active ingredients absorbed via the intestinal glucose transport pathway.

Left atrial appendage strain predicts subclinical atrial fibrillation in embolic strokes of undetermined source.

Left atrial (LA) strain is promising in prediction of clinical atrial fibrillation (AF) in stroke patients. However, prediction of subclinical AF is critical in patients with embolic strokes of undetermined source (ESUS). The aim of this prospective study was to investigate novel LA and left atrial appendage (LAA) strain markers in prediction of subclinical AF in ESUS patients. A total of 185 patients with ESUS, mean age 68 ± 13years, 33% female, without diagnosed AF, were included. LAA and LA function by conventional echocardiographic parameters and reservoir strain (Sr), conduit strain (Scd), contraction strain (Sct), and mechanical dispersion (MD) of Sr were assessed with transoesophageal and transthoracic echocardiography. Subclinical AF was detected by insertable cardiac monitors during follow-up. LAA strain was impaired in 60 (32%) patients with subclinical AF compared to those with sinus rhythm: LAA-Sr, 19.2 ± 4.5% vs. 25.6 ± 6.5% (P < 0.001); LAA-Scd, -11.0 ± 3.1% vs. -14.4 ± 4.5% (P < 0.001); and LAA-Sct, -7.9 ± 4.0% vs. -11.2 ± 4% (P < 0.001), respectively, while LAA-MD was increased, 34 ± 24 ms vs. 26 ± 20 ms (P = 0.02). However, there was no significant difference in phasic LA strain or LA-MD. By ROC analyses, LAA-Sr was highly significant in prediction of subclinical AF and showed the best AUC of 0.80 (95% CI 0.73-0.87) with a sensitivity of 80% and a specificity of 73% (P < 0.001). LAA-Sr and LAA-MD were both independent and incremental markers of subclinical AF in ESUS patients. LAA function by strain and mechanical dispersion predicted subclinical AF in ESUS patients. These novel echocardiographic markers may improve risk stratification in ESUS patients.

Influence of walking on knee ligament response in car-to-pedestrian collisions.

Pedestrians are likely to experience walking before accidents. The walking process imposes cyclic loading on knee ligaments and increases knee joint temperature. Both cyclic loading and temperature affect the material properties of ligaments, which further influence the risk of ligament injury. However, the effect of such walking-induced material property changes on pedestrian ligament response has not been considered. Therefore, in this study, we investigated the influence of walking on ligament response in car-to-pedestrian collisions. Using Total Human Model for Safety (THUMS) model, knee ligament responses (i.e., cross-sectional force and local strain) were evaluated under several crash scenarios (i.e., two impact speeds, two knee contact heights, and three pedestrian postures). In worst case scenarios, walking-induced changes in ligament material properties led to a 10% difference in maximum local strain and a 6% difference in maximum cross-sectional force. Further considering the material uncertainty caused by experimental dispersion, the ligament material property changes due to walking resulted in a 28% difference in maximum local strain and a 26% difference in maximum cross-sectional force. This study demonstrates the importance of accounting for walking-induced material property changes for the reliability of safety assessments and injury analysis.

Characterization of pain-, anxiety-, and cognition-related behaviors in the complete Freund's adjuvant model of chronic inflammatory pain in Wistar-Kyoto rats.

Chronic pain is often associated with comorbid anxiety and cognitive dysfunction, negatively affecting therapeutic outcomes. The influence of genetic background on such interactions is poorly understood. The stress-hyperresponsive Wistar-Kyoto (WKY) rat strain, which models aspects of anxiety and depression, displays enhanced sensitivity to noxious stimuli and impaired cognitive function, compared with Sprague-Dawley (SD) counterparts. However, pain- and anxiety-related behaviors and cognitive impairment following induction of a persistent inflammatory state have not been investigated simultaneously in the WKY rats. Here we compared the effects of complete Freund's adjuvant (CFA)-induced persistent inflammation on pain-, negative affect- and cognition-related behaviors in WKY vs. SD rats. Male WKY and SD rats received intra-plantar injection of CFA or needle insertion (control) and, over the subsequent 4 weeks, underwent behavioral tests to assess mechanical and heat hypersensitivity, the aversive component of pain, and anxiety- and cognition-related behaviors. The CFA-injected WKY rats exhibited greater mechanical but similar heat hypersensitivity compared to SD counterparts. Neither strain displayed CFA-induced pain avoidance or anxiety-related behavior. No CFA-induced impairment was observed in social interaction or spatial memory in WKY or SD rats in the three-chamber sociability and T-maze tests, respectively, although strain differences were apparent. Reduced novel object exploration time was observed in CFA-injected SD, but not WKY, rats. However, CFA injection did not affect object recognition memory in either strain. These data indicate exacerbated baseline and CFA-induced mechanical hypersensitivity, and impairments in novel object exploration, and social and spatial memory in WKY vs. SD rats.

Energy-dispersive X-ray stress analysis under geometric constraints: exploiting the material's inherent anisotropy.

Two data evaluation concepts for X-ray stress analysis based on energy-dispersive diffraction on polycrystalline materials with cubic crystal structure, almost random crystallographic texture and strong single-crystal elastic anisotropy are subjected to comparative assessment. The aim is the study of the residual stress state in hard-to-reach measurement points, for which the sin2ψ method is not applicable due to beam shadowing at larger sample tilting. This makes the approaches attractive for stress analysis in engineering parts with complex shapes, for example. Both approaches are based on the assumption of a biaxial stress state within the irradiated sample volume. They exploit in different ways the elastic anisotropy of individual crystallites acting at the microscopic scale and the anisotropy imposed on the material by the near-surface stress state at the macroscopic scale. They therefore complement each other, in terms of both their preconditions and their results. The first approach is based on the evaluation of strain differences, which makes it less sensitive to variations in the strain-free lattice parameter a 0. Since it assumes a homogeneous stress state within the irradiated sample volume, it provides an average value of the in-plane stresses. The second approach exploits the sensitivity of the lattice strain to changes in a 0. Consequently, it assumes a homogeneous chemical composition but provides a stress profile within the information depth. Experimental examples from different fields in materials science, namely shot peening of austenitic steel and in situ stress analysis during welding, are presented to demonstrate the suitability of the proposed methods.

The influence of out-of-plane motion on the deformation measurement of planar biaxial tests on biological soft tissue

Planar biaxial testing is a popular technique to characterize a wide range of biological soft tissues. Nevertheless, a lot of variability exists between experimental setups. One particularly important variation relates to the difference in strain measuring techniques to characterize the deformation during the test: digital image correlation using one camera (measuring the out-of-plane motion as false strain), or two cameras (providing a stereo view). This study aimed to compare the two methods and provide practical guidelines for their use. A planar biaxial experiment was performed on ovine arterial samples on which both methods produced similar results in terms of strain measurements and material properties. The two-dimensional approach using a single camera is an appropriate and less time-consuming alternative to measure the deformation of soft biological tissue during planar biaxial loading conditions for similar setups.

Study on the crack nucleation mechanism of Ti-2Al-2.5Zr alloy in low cycle fatigue: Quasi in-situ experiments and crystal plasticity simulation

The fatigue crack nucleation mechanism of Ti-2Al-2.5Zr alloy was investigated using the coupling method of quasi in-situ tests with crystal plasticity (CP) simulation. The constitutive parameters in the CP model were validated by digital image correlation based on scanning electron microscope (SEM-DIC). It was found that the transgranular and intergranular cracks nucleated inside grains and at grain boundaries (GBs), respectively, due to slip intrusions/extrusions along prismatic planes with highest SFpris. values, while quasi transgranular cracks were induced by the adjacent microstructure or cracks. The angle Ω between the sample surface and the slip direction of slip planes where the transgranular cracks nucleated was within the range of 20–55°. Three factors for predicting intergranular cracks were identified, and the slip shearing mechanism of GBs was proposed. The CP results revealed that a significant plastic strain difference was generated at GBs where intergranular cracks nucleated. The band averaging method showed better prediction ability than the grain averaging method, and a unified fatigue indicator parameter (FIP) combining the accumulated plastic strain, the strain incompatibility parameter (SIP), and the abovementioned crack prediction factors, was proposed, which improved the unified prediction ability for both transgranular and intergranular cracks.

High-precision spatial analysis of mouse courtship vocalization behavior reveals sex and strain differences

Mice display a wide repertoire of vocalizations that varies with sex, strain, and context. Especially during social interaction, including sexually motivated dyadic interaction, mice emit sequences of ultrasonic vocalizations (USVs) of high complexity. As animals of both sexes vocalize, a reliable attribution of USVs to their emitter is essential. The state-of-the-art in sound localization for USVs in 2D allows spatial localization at a resolution of multiple centimeters. However, animals interact at closer ranges, e.g. snout-to-snout. Hence, improved algorithms are required to reliably assign USVs. We present a novel algorithm, SLIM (Sound Localization via Intersecting Manifolds), that achieves a 2–3-fold improvement in accuracy (13.1–14.3 mm) using only 4 microphones and extends to many microphones and localization in 3D. This accuracy allows reliable assignment of 84.3% of all USVs in our dataset. We apply SLIM to courtship interactions between adult C57Bl/6J wildtype mice and those carrying a heterozygous Foxp2 variant (R552H). The improved spatial accuracy reveals that vocalization behavior is dependent on the spatial relation between the interacting mice. Female mice vocalized more in close snout-to-snout interaction while male mice vocalized more when the male snout was in close proximity to the female's ano-genital region. Further, we find that the acoustic properties of the ultrasonic vocalizations (duration, Wiener Entropy, and sound level) are dependent on the spatial relation between the interacting mice as well as on the genotype. In conclusion, the improved attribution of vocalizations to their emitters provides a foundation for better understanding social vocal behaviors.

Assessing health, psychological distress and financial well-being in informal young adult caregivers compared to matched young adult non-caregivers

ABSTRACT Young adult caregivers (YACs) are faced with the atypical challenge of providing informal (i.e. not paid) care to a family member, while simultaneously at a critical developmental stage in which many major life decisions and milestones are taking place. Adding the challenge of caring for a family member during this already complex time period may have a detrimental impact on young adults’ (YAs) own overall health and well-being. The aim of this study was to examine differences in overall health, psychological distress, and financial strain among a propensity matched sample of YACs compared to young adult non-caregivers (YANCs) from a nationally representative database and to examine differences in these outcomes by caregiving role (caring for a child vs. other family member). YAs (aged 18–39, N = 178) identifying as a caregiver (n = 74) were matched with YANCs (n = 74) on age, gender, and race. Results revealed that YACs exhibited higher psychological distress, lower overall health and more sleep disturbance and higher financial strain compared to YANCs. YAs caring for family members other than children also reported higher anxiety and fewer hours spent caregiving compared to YAs caring for a child. YACs appear to be at risk for impairments in health and well-being compared to their matched peers. Longitudinal research is needed to understand how caregiving during young adulthood impacts health and well-being across time.

Early detection and serial monitoring during chemotherapy-radiation therapy: Using T1 and T2 mapping cardiac magnetic resonance imaging.

To confirm the ability of native T1 and T2 values in detecting and monitoring early myocardial injuries of chest radiotherapy in neoplasm patients. Fifteen participants received non-anthracycline chemotherapy and chest radiotherapy, and 30 age/gender-matched controls were enrolled in this prospective study. Cardiac magnetic resonance scans were performed within 2 days, 3 months, and 6 months after chest radiotherapy. Myocardial native T1 and T2 values were measured in irradiated and nonirradiated areas. Meanwhile, the parameters of left ventricular function and left ventricular myocardial strain were obtained. There were no significant differences in left ventricular function, native T1, T2, and strain between patients and controls before chest radiotherapy. In 15 participants who were followed up for 6 months, there was a significant change only in left ventricular ejection fraction (LVEF) among baseline and the first follow-up (P = 0.021), while the adjusted P-value was higher than 0.05 after Bonferroni correction, as well as other parameters. Native T1 values were elevated at 3 and 6 months in irradiated areas compared with baseline (1,288.72 ± 66.59 ms vs. 1,212.51 ± 45.41 ms; 1,348.01 ± 54.16 ms vs. 1,212.51 ± 45.41 ms; P < 0.001 for both). However, T2 values only changed at 3 months in irradiated areas compared with baseline (44.21 ± 3.35 ms vs. 39.14 ± 1.44 ms; P = 0.006). Neither the native T1 nor T2 values changed in nonirradiated areas during the follow-up period (all P > 0.05). There were no significant differences in strain changes during the follow-up period (all P > 0.05). Native T1 and T2 values elevated at 3 months after chest radiotherapy, whereas LVEF showed no significant change during the 6-month follow-up.

Estimation of left ventricular activation sequence in patients with heart failure using two-dimensional speckle tracking echocardiography

Evaluation of longitudinal strain (LS) from two-dimensional echocardiography is useful for global and regional left ventricular (LV) dysfunction assessment. We determined whether the LS reflects contraction process in patients with asynchronous LV activation. We studied 144 patients with an ejection fraction ≤ 35%, who had left bundle branch block (LBBB, n = 42), right ventricular apical (RVA) pacing (n = 34), LV basal- or mid-lateral pacing (n = 23), and no conduction block (Narrow-QRS, n = 45). LS distribution maps were constructed using 3 standard apical views. The times from the QRS onset-to-early systolic positive peak (Q-EPpeak) and late systolic negative peak (Q-LNpeak) were measured to determine the beginning and end of contractions in each segment. Negative strain in LBBB initially appeared in the septum and basal-lateral contracted late. In RVA and LV pacing, the contracted area enlarged centrifugally from the pacing site. Narrow-QRS showed few regional differences in strain during the systolic period. The Q-EPpeak and Q-LNpeak exhibited similar sequences characterized by septum to basal-lateral via the apical regions in LBBB, apical to basal regions in RVA pacing, and lateral to a relatively large delayed contracted area between the apical- and basal-septum in LV pacing. Differences in Q-LNpeaks between the apical and basal segments in delayed contracted wall were 107 ± 30 ms in LBBB, 133 ± 46 ms in RVA pacing, and 37 ± 20 ms in LV pacing (p < 0.05, between QRS groups). Specific LV contraction processes were demonstrated by evaluating the LS distribution and time-to-peak strain. These evaluations may have potential to estimate the activation sequence in patients with asynchronous LV activation.

Contribution of MALDI‐TOF‐MS‐based principal component analysis for distinguishing foodborne pathogens

AbstractFoodborne diseases are important to determine bacteria in strain level, which are analyzed by library‐based devices and bioinformatics‐enabled. The aim of this study was to investigate the contribution of principal component analysis (PCA) with matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (MALDI‐TOF‐MS) to distinguish according to the differences of bacterial strains as rapidly screening of foodborne bacteria. The MALDI‐TOF‐MS‐based PCA analysis was used for differentiating bacterial strains isolated from ready‐to‐eat foods. According to the results of PCA analysis, the percentages of distance and proximity between species were evaluated by composite correlation indexes (CCI). Bacillus cereus were detected in burghul salad (BC1) and macaroni salad (BC2) taken from the SB2‐snack bar, and the similarity rate was determined as 97%. Three other B. cereus bacteria (BC3, BC4, and BC5) in the same cluster were also isolated from salads collected from SB4‐snack bar. The similarity of Klebsiella pneumoniae bacteria, which have the codes KP1 and KP2, isolated from macaroni salad and burghul salad taken from the SB2 snack bar respectively were 96%. Additionally, the CCI values of two E. coli strains in burghul (EC1) salad and Russian salad (EC2) in the same sampling point (SB1) were determined as 97%. In conclusion, this analysis with MALDI‐TOF‐MS based PCA has revealed the relationships between bacteria genera and species, beyond just the identification of bacteria and the rapid screening of bacteria in perishable foodstuffs. Similarities between bacterial strains identified for different samples from the same sampling point suggested that there were not adequate hygiene rules and storage requirements were not followed.

Enhanced Production of Lipstatin Through NTG Treatment of Streptomyces toxytricini KD18 at 5 L Bioreactor Level.

Lipstatin, natural inhibitor of pancreatic lipase produced by Streptomyces toxytricini and used as an anti-obesity drug. Chemical mutagenesis was performed with different concentrations of N-methyl-N'-nitro-N-nitrosoguanidine (NTG) for strain improvement to obtain high yield of lipstatin. It was observed that the potential of the wild type strain to produce lipstatin (1.09 g/L) was very low. Selected mutants produced lipstatin in the range of 1.20-2.23 g/L at the flask level where maximum amount of lipstatin was produced by M5 mutant. For comparative study, both the parent and M5 mutant strain of S. toxytricini were grown at the lab scale bioreactor with suitable sources of carbon and nitrogen. Significant increase in the production of lipstatin was observed at the bioreactor level where the wild type strain produced 2.4 g/L of lipstatin, while through the NTG mutation, the production of lipstatin was 5.35 g/L. However, Dry Cell Weight (DCW) of the mutant strain was less in comparison with wild type strain and significant morphological differences were observed. Nearly 5 times increase in the production of lipstatin was achieved through NTG mutation and bioreactor-controlled conditions. It was determined that the NTG treatment might be beneficial for strain improvement to get a better candidate for lipstatin production on commercial scale.

An evaluation of morningness and schedule misfit using the revised Preferences Scale (PS-6): Implications for work and health outcomes among healthcare workers

ABSTRACT The last several decades of shift work tolerance and circadian misalignment research has had mixed results regarding the adverse impact of shift work on work and health outcomes. This inconsistency is, in part, due to the circadian typology measure employed and the study methodology. Based on models of shift work and health, the present study examined associations between circadian misalignment, end-of-day strain, and job- and health-related outcomes using the revised Preferences Scale (PS-6). A sample of 129 healthcare workers (76.7% female) from the United States (67%) and Australia (34.1%) aged 22 to 64 responded to a self-report questionnaire on work schedules, work stressors, and well-being. Multiple regression analysis found that the preferences for cognitive activity subscale of the PS-6 moderated the association between shift work and strain (b = −.36, p < .001). Those who worked nights experienced more strain if their preferences for cognitive activity were misaligned, whereas no differences in strain were observed among day workers. Moderated-mediation analyses, on the basis 95% confidence intervals, found that shift work had a conditional indirect effect on work-family conflict, job satisfaction, and health-related quality of life, via strain, and the effect was moderated by preferences for cognitive activity. Findings provide additional evidence for the criterion and external validity of the PS-6, and importantly, the present study establishes further support for models of shift work and health. Overall, the analyses highlight the importance of exploring the interactions between shift work and different dimensions of morningness in shift work tolerance research.