RNF149 Destabilizes IFNGR1 in Macrophages to Favor Post-Infarction Cardiac Repair.

BACKGROUND: Macrophage-driven inflammation critically involves in cardiac injury and repair following myocardial infarction (MI). However, the intrinsic mechanisms that halt the immune response of macrophages, which is critical to preserve homeostasis and effective infarct repair, remain to be fully defined. Here, we aimed to determine the ubiquitination-mediated regulatory effects on averting exaggerated inflammatory responses in cardiac macrophages. METHODS: We used transcriptome analysis of mouse cardiac macrophages and bone marrow-derived macrophages to identify the E3 ubiquitin ligase RNF149 (RING finger protein 149) as a modulator of macrophage response to MI. Employing loss-of-function methodologies, bone marrow transplantation approaches, and adenovirus-mediated RNF149 overexpression in macrophages, we elucidated the functional role of RNF149 in MI. We explored the underlying mechanisms through flow cytometry, transcriptome analysis, immunoprecipitation/mass spectrometry analysis, and functional experiments. RNF149 expression was measured in the cardiac tissues of patients with acute MI and healthy controls. RESULTS: RNF149 was highly expressed in murine and human cardiac macrophages at the early phase of MI. Knockout of RNF149, transplantation of Rnf149-/- bone marrow, and bone marrow macrophage-specific RNF149-knockdown markedly exacerbated cardiac dysfunction in murine MI models. Conversely, overexpression of RNF149 in macrophages attenuated the ischemia-induced decline in cardiac contractile function. RNF149 deletion increased infiltration of proinflammatory monocytes/macrophages, accompanied by a hastened decline in reparative subsets, leading to aggravation of myocardial apoptosis and impairment of infarct healing. Our data revealed that RNF149 in infiltrated macrophages restricted inflammation by promoting ubiquitylation-dependent proteasomal degradation of IFNGR1 (interferon gamma receptor 1). Loss of IFNGR1 rescued deleterious effects of RNF149 deficiency on MI. We further demonstrated that STAT1 activation induced Rnf149 transcription, which, in turn, destabilized the IFNGR1 protein to counteract type-II IFN (interferon) signaling, creating a feedback control mechanism to fine-tune macrophage-driven inflammation. CONCLUSIONS: These findings highlight the significance of RNF149 as a molecular brake on macrophage response to MI and uncover a macrophage-intrinsic posttranslational mechanism essential for maintaining immune homeostasis and facilitating cardiac repair following MI.

Honokiol ameliorates angiotensin II-induced cardiac hypertrophy by promoting dissociation of the Nur77-LKB1 complex and activating the AMPK pathway.

Pathological cardiac hypertrophy is a key contributor to heart failure, and the molecular mechanisms underlying honokiol (HNK)-mediated cardioprotection against this condition remain worth further exploring. This study aims to investigate the effect of HNK on angiotensin II (Ang II)-induced myocardial hypertrophy and elucidate the underlying mechanisms. Sprague-Dawley rats were exposed to Ang II infusion, followed by HNK or vehicle treatment for 4 weeks. Our results showed that HNK treatment protected against Ang II-induced myocardial hypertrophy, fibrosis and dysfunction in vivo and inhibited Ang II-induced hypertrophy in neonatal rat ventricular myocytes in vitro. Mechanistically, HNK suppressed the Ang II-induced Nur77 expression at the transcriptional level and promoted ubiquitination-mediated degradation of Nur77, leading to dissociation of the Nur77-LKB1 complex. This facilitated the translocation of LKB1 into the cytoplasm and activated the LKB1-AMPK pathway. Our findings suggest that HNK attenuates pathological remodelling and cardiac dysfunction induced by Ang II by promoting dissociation of the Nur77-LKB1 complex and subsequent activation of AMPK signalling. This study uncovers a novel role of HNK on the LKB1-AMPK pathway to protect against cardiac hypertrophy.

Frontiers in plant RNA research in ICAR2023: from lab to innovative agriculture.

The recent growth in global warming, soil contamination, and climate instability have widely disturbed ecosystems, and will have a significant negative impact on the growth of plants that produce grains, fruits and woody biomass. To conquer this difficult situation, we need to understand the molecular bias of plant environmental responses and promote development of new technologies for sustainable maintenance of crop production. Accumulated molecular biological data have highlighted the importance of RNA-based mechanisms for plant stress responses. Here, we report the most advanced plant RNA research presented in the 33rd International Conference on Arabidopsis Research (ICAR2023), held as a hybrid event on June 5-9, 2023 in Chiba, Japan, and focused on "Arabidopsis for Sustainable Development Goals". Six workshops/concurrent sessions in ICAR2023 targeted plant RNA biology, and many RNA-related topics could be found in other sessions. In this meeting report, we focus on the workshops/concurrent sessions targeting RNA biology, to share what is happening now at the forefront of plant RNA research.

Association between microcirculation in spontaneous breathing trial and extubation success.

PURPOSE: This study assessed the association between changes in sublingual microcirculation after a spontaneous breathing trial (SBT) and successful extubation. MATERIALS AND METHODS: Sublingual microcirculation was assessed using an incident dark-field video microscope before and after each SBT and before extubation. Microcirculatory parameters before the SBT, at the end of the SBT, and before extubation were compared between the successful and failed extubation groups. RESULTS: Forty-seven patients were enrolled and analysed in this study (34 patients in the successful extubation group and 13 patients in the failed extubation group). At the end of the SBT, the weaning parameters did not differ between the two groups. However, the total small vessel density (21.2 [20.4-23.7] versus 24.9 [22.6-26.5] mm/mm2), perfused small vessel density (20.6 [18.5-21.8] versus 23.1 [20.9-25] mm/mm2), proportion of perfused small vessels (91 [87-96] versus 95 [93-98] %), and microvascular flow index (2.8 [2.7-2.9] versus 2.9 [2.9-3]) were significantly lower in the failed extubation group than in the successful extubation group. The weaning and microcirculatory parameters did not differ significantly between the two groups before the SBT. CONCLUSIONS: More patients are required to investigate the difference between baseline microcirculation before a successful SBT and the change in microcirculation at the end of the SBT between the successful and failed extubation groups. Better sublingual microcirculatory parameters at the end of SBT and before extubation are associated with successful extubation.

Prognostic value of the post-exercise heart rate recovery and BHDE-index in chronic obstructive pulmonary disease.

BACKGROUND: The BODE index, consisting of body mass index (B), airflow obstruction (O), dyspnea score (D), and exercise capacity (E), can predict outcomes in COPD. However, when spirometry was restricted to prevent cross-infection such as COVID-19 pandemic, a modified index would be needed. Because cardiovascular dysfunction is associated with poor clinical outcomes in COPD, we conducted a novel BHDE-index by replacing spirometry with post-exercise heart rate recovery (HRR, H) and evaluated its predictive performance in this observational study. METHODS: From January 2019 to December 2019, enrolled patients were analyzed as a derivation cohort for the setup of the model. This model was verified in another group of patients generated between January 2020 and December 2020, as the validation cohort. The post exercise HRR was defined as the difference of heart rate immediately after and 1 min after test cessation. RESULTS: A total of 447 patients with COPD were enrolled. Patients with abnormal HRR were older, with more severe airway obstruction, severe airway symptoms, faster resting heart rate, shorter 6-min walk distance and higher frequency of severe acute exacerbation in previous one year. The prediction performance of the BHDE-index for one-year severe COPD exacerbation was similar to that of the BODE-index in both the derivation and validation groups [area under the receiver operating characteristic curve (AUROC) 0.76 vs. 0.75, p = 0.369; AUROC 0.74 vs. 0.79, p = 0.05]. The prediction performance for 1 year mortality was also similar between BHDE-index and BODE-index in both cohorts [AUROC 0.80 vs. 0.77, p = 0.564; 0.76 vs. 0.70, p = 0.234]. Univariate and multivariate analyses also showed that the BHDE-index was an independent and important predictor of annual severe COPD exacerbation in the derivation and validation cohorts. CONCLUSIONS: The BHDE-index is a good and easy-to-perform prediction model for the risk of severe acute exacerbation and 1-year mortality in COPD wherever spirometry results are unavailable.

Lgr4 Governs a Pro-Inflammatory Program in Macrophages to Antagonize Post-Infarction Cardiac Repair.

RATIONALE: Macrophages are critically involved in wound healing following myocardial infarction (MI). Lgr4, a member of LGR (leucine-rich repeat-containing G protein-coupled receptor) family, is emerging as a regulator of macrophage-associated immune responses. However, the contribution of Lgr4 to macrophage phenotype and function in the context of MI remains unclear. OBJECTIVE: To determine the role of macrophage Lgr4 in MI and to dissect the underlying mechanisms. METHODS AND RESULTS: During early inflammatory phase of MI, infarct macrophages rather than neutrophils expressed high level of Lgr4. Macrophage-specific Lgr4 knockout mice had no baseline cardiovascular defects but manifested improved heart function, modestly reduced infarct size, decreased early mortality due to cardiac rupture, and ameliorated adverse remodeling after MI. Improved outcomes in macrophage-specific Lgr4 knockout mice subjected to MI were associated with mitigated ischemic injury and optimal infarct healing, as determined by reduction of cardiac apoptosis in the peri-infarct zone, attenuation of local myocardial inflammatory response, decrease of matrix metalloproteinase expression in the infarct, enhancement of angiogenesis, myofibroblast proliferation, and collagen I deposition in reparative granulation tissue as well as formation of collagen-rich scar. More importantly, macrophage-specific Lgr4 knockout infarcts had reduced numbers of infiltrating leukocytes and inflammatory macrophages but harbored abundant reparative macrophage subsets. Lgr4-null infarct macrophages exhibited a less inflammatory transcriptional signature. These findings were further supported by transcriptomic profiling data showing repression of multiple pathways and broad-spectrum genes associated with proinflammatory responses in macrophage-specific Lgr4 knockout infarcts. Notably, we discovered that Lgr4-mediated functional phenotype programing in infarct macrophages was at least partly attributed to regulation of AP (activator protein)-1 activity. We further demonstrated that the synergistic effects of Lgr4 on AP-1 activation in inflammatory macrophages occurred via enhancing CREB (cAMP response element-binding protein)-mediated c-Fos, Fosl1, and Fosb transactivation. CONCLUSIONS: Together, our data highlight the significance of Lgr4 in governing proinflammatory phenotype of infarct macrophages and postinfarction repair.

Gender equity in ergonomics: does muscle effort in laparoscopic surgery differ between men and women?

BACKGROUND: Women surgeons may experience more ergonomic challenges while performing surgery. We aimed to assess ergonomics between men and women surgeons. METHODS: Laparoscopic surgeons from a single institution were enrolled. Demographics and intraoperative data were collected. Muscle groups were evaluated objectively using surface electromyography (EMG; TrignoTM, Delsys, Inc., Natick, MA), and comprised upper trapezius (UT), anterior deltoid, flexor carpi radialis (FCR), and extensor digitorum (ED). Comparisons were made between women (W) and men (M) for each muscle group, assessing maximal voluntary contraction (MVC) and median frequency (MDF). The Piper Fatigue Scale-12 (PFS-12) was used to assess self-perceived fatigue. Statistical analyses were performed using SPSS v26.0, α = 0.05. RESULTS: 18 surgeries were recorded (W:8, M:10). Women had higher activation of UT (32% vs 23%, p < 0.001), FCR (33% vs 16%, p < 0.001), and ED (13% vs 10%, p < 0.001), and increased effort of ED (90.4 ± 18.13 Hz vs 99.1 ± 17.82 Hz). Comparisons were made between W and M for each muscle group, assessing MVC and MDF. CONCLUSIONS: After controlling for surgeon's height and duration of surgery, an increase in muscle activation was seen for women laparoscopic surgeons. Since poor ergonomics could be a major cause of work-related injuries, we must understand differences in ergonomics between men and women and evaluate which factors impact these variations.

Impact of Age on Outcome of Rifapentine-Based Weekly Therapy for Latent Tuberculosis Infection.

BACKGROUND: Weekly rifapentine and isoniazid (3HP) is gaining popularity for latent tuberculosis infection treatment because of its short course and high completion rate. Prior to widespread use, comprehensive 3HP treatment assessment covering an all-age population is essential. METHODS: Participants receiving ≥1 3HP dose from September 2014 to December 2019 were stratified into elderly (≥65 years), middle-aged (>35 & <65 years), and younger (≤35 years) age groups. This study investigated the impact of age on treatment outcome, particularly systemic drug reactions (SDRs) and 3HP discontinuation. RESULTS: Overall, 134 of 579 (23.1%) participants were elderly. The completion rate was 83.1% overall and was highest and lowest in the younger group (94.5%) and elderly (73.9%) group, respectively. However, the 3HP discontinuation rate was not significantly different among the 3 groups in multivariate logistic regression analysis. In total, 362 (62.5%) participants experienced 1 or more adverse drug reactions (ADRs), of which 38 (10.5%) and 98 (27.1%) required temporary and permanent treatment interruption, respectively. The SDR risk was 11.2% in overall and 17.1% in the middle-aged group, 3.04-fold higher than that in the elderly group (P = .025). This finding was consistently observed in different clinical settings. Hypertensive events accompanied with flu-like symptoms occurred in 11.2% of elderly participants, and accounted for 50% of grade ≥3 ADRs. CONCLUSIONS: With proper medical support and programmatic follow-up, the 3HP completion rate is >70% even in elderly participants. In middle-aged and elderly individuals, 3HP should be employed with caution because of risk of SDRs and hypertensive events, respectively. Summary: Under programmatic medical support, widespread use of weekly rifapentine and isoniazid (3HP) for latent tuberculosis treatment is possible for its high completion rate. 3HP should be employed with caution for risk of systemic drug reactions and hypertensive events in middle-aged and elderly individuals, respectively.

Application of transthoracic shear-wave ultrasound elastography in lung lesions.

INTRODUCTION: Tissue stiffness information may help in the diagnosis of lung lesions. This study aimed to investigate and validate the application of transthoracic two-dimensional shear-wave ultrasound elastography in differentiating malignant from benign subpleural lung lesions. METHODS: This study involved one retrospective observational derivation cohort from January 2016 to December 2017 and one prospective observational validation cohort from December 2017 to December 2019. The inclusion criterion was radiographic evidence of pulmonary lesions. The patients were categorised into air bronchogram and hypoechoic groups based on B-mode grayscale images. The elasticity of subpleural lung lesions with acceptable shear-wave propagation was measured. Diagnoses were made on the basis of pathology, microbiological studies or following up the clinical course for at least 6 months. RESULTS: A total of 354 patients were included. Among the 121 patients in the derivation cohort, a receiver operating characteristic curve was constructed and the cut-off point to differentiate benign from malignant lesions was 65 kPa with a Youden index of 0.60 and an accuracy of 84.3%. Among the 233 patients in the validation cohort, the diagnostic performance was maintained, with a Youden index of 0.65 and an accuracy of 86.7%. Upon applying the cut-off point to the air bronchogram group, the Youden index was 0.70 and the accuracy was 85.0%. CONCLUSIONS: This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy.

DEAD-Box RNA Helicase 42 Plays a Critical Role in Pre-mRNA Splicing under Cold Stress.

Low temperature is an important environmental stress that adversely affects rice (Oryza sativa) growth and productivity. Splicing of pre-mRNA is a crucial posttranscriptional regulatory step in gene expression in plants and is sensitive to temperature. DEAD-box RNA helicases belong to an RNA helicase family involved in the rearrangement of ribonucleoprotein complexes and the modification of RNA structure and are therefore involved in all aspects of RNA metabolism. In this study, we demonstrate that the rate of pre-mRNA splicing is reduced in rice at low temperatures and that the DEAD-box RNA Helicase42 (OsRH42) is necessary to support effective splicing of pre-mRNA during mRNA maturation at low temperatures. OsRH42 expression is tightly coupled to temperature fluctuation, and OsRH42 is localized in the splicing speckles and interacts directly with U2 small nuclear RNA. Retarded pre-mRNA splicing and plant growth defects were exhibited by OsRH42-knockdown transgenic lines at low temperatures, thus indicating that OsRH42 performs an essential role in ensuring accurate pre-mRNA splicing and normal plant growth under low ambient temperature. Unexpectedly, our results show that OsRH42 overexpression significantly disrupts the pre-mRNA splicing pathway, causing retarded plant growth and reducing plant cold tolerance. Combined, these results indicate that accurate control of OsRH42 homeostasis is essential for rice plants to respond to changes in ambient temperature. In addition, our study presents the molecular mechanism of DEAD-box RNA helicase function in pre-mRNA splicing, which is required for adaptation to cold stress in rice.

Integrative utility of long read sequencing-based whole genome analysis and phenotypic assay on differentiating isoniazid-resistant signature of Mycobacterium tuberculosis.

BACKGROUND: With the advancement of next generation sequencing technologies (NGS), whole-genome sequencing (WGS) has been deployed to a wide range of clinical scenarios. Rapid and accurate classification of drug-resistant Mycobacterium tuberculosis (MTB) would be advantageous in reducing the amplification of additional drug resistance and disease transmission. METHODS: In this study, a long-read sequencing approach was subjected to the whole-genome sequencing of clinical MTB clones with susceptibility test profiles, including isoniazid (INH) susceptible clones (n = 10) and INH resistant clones (n = 42) isolated from clinical specimens. Non-synonymous variants within the katG or inhA gene associated with INH resistance was identified using Nanopore sequencing coupled with a corresponding analytical workflow. RESULTS: In total, 54 nucleotide variants within the katG gene and 39 variants within the inhA gene associated with INH resistance were identified. Consistency among the results of genotypic profiles, susceptibility test, and minimal inhibitory concentration, the high-INH resistance signature was estimated using the area under the receiver operating characteristic curve with the existence of Ser315Thr (AUC = 0.822) or Thr579Asn (AUC = 0.875). CONCLUSIONS: Taken together, we curated lists of coding variants associated with differential INH resistance using Nanopore sequencing, which may constitute an emerging platform for rapid and accurate identification of drug-resistant MTB clones.

Etiology-associated heterogeneity in acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Heterogeneity in acute respiratory distress syndrome (ARDS) has led to many statistically negative clinical trials. Etiology is considered an important source of pathogenesis heterogeneity in ARDS but previous studies have usually adopted a dichotomous classification, such as pulmonary versus extrapulmonary ARDS, to evaluate it. Etiology-associated heterogeneity in ARDS remains poorly described. METHODS: In this retrospective cohort study, we described etiology-associated heterogeneity in gas exchange abnormality (PaO2/FiO2 [P/F] and ventilatory ratios), hemodynamic instability, non-pulmonary organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score, biomarkers of inflammation and coagulation, and 30-day mortality. Linear regression was used to model the trajectory of P/F ratios over time. Wilcoxon rank-sum tests, Kruskal-Wallis rank tests and Chi-squared tests were used to compare between-etiology differences. RESULTS: From 1725 mechanically ventilated patients in the ICU, we identified 258 (15%) with ARDS. Pneumonia (48.4%) and non-pulmonary sepsis (11.6%) were the two leading causes of ARDS. Compared with pneumonia associated ARDS, extra-pulmonary sepsis associated ARDS had a greater P/F ratio recovery rate (difference = 13 mmHg/day, p = 0.01), more shock (48% versus 73%, p = 0.01), higher non-pulmonary SOFA scores (6 versus 9 points, p < 0.001), higher d-dimer levels (4.2 versus 9.7 mg/L, p = 0.02) and higher mortality (43% versus 67%, p = 0.02). In pneumonia associated ARDS, there was significant difference in proportion of shock (p = 0.005) between bacterial and non-bacterial pneumonia. CONCLUSION: This study showed that there was remarkable etiology-associated heterogeneity in ARDS. Heterogeneity was also observed within pneumonia associated ARDS when bacterial pneumonia was compared with other non-bacterial pneumonia. Future studies on ARDS should consider reporting etiology-specific data and exploring possible effect modification associated with etiology.

High-power and single-mode VCSEL arrays with single-polarized outputs by using package-induced tensile strain.

In this work, we demonstrate a novel high-power vertical-cavity surface-emitting laser (VCSEL) array with highly single-mode (SM) and single-polarized output performance without significantly increasing the intra-cavity loss and threshold current (Ith). By combining a low-loss zinc-diffusion aperture with an electroplated copper substrate, we can obtain a highly SM output (side mode suppression ratio >50dB) with a very narrow divergence angle (1/e2:∼10∘) under high output power (3.1 W; 1% duty cycle) and sustain a single polarization state, with a polarization suppression ratio of around 9 dB, under the full range of bias currents. Compared to the reference device without the copper substrate, the demonstrated array can not only switch the output optical spectra from quasi-SM to highly SM but also maintain a close threshold current value (Ith: 0.8 versus 0.7 mA per unit device) and slope efficiency. The enhancement in fundamental mode selectivity of our VCSEL structure can be attributed to the single-polarized lasing mode induced by tensile strain, which is caused by the electroplated copper substrate, as verified by the double-crystal x-ray measurement results.

Diagnostic performance of FDG PET/CT in critically ill patients with suspected infection: A systematic review and meta-analysis.

BACKGROUND/PURPOSE: Nuclear imaging, including gallium scintigraphy and fluorodeoxyglucose (FDG) positron emission tomography (PET), has been widely used to identify focus of infection in fever of unknown origin. However, little is known about its role in critically ill patients, who are usually with multiple inflammatory foci and unable to tolerate long image acquisition time. This systematic review aimed to evaluate the diagnostic performance of FDG PET for suspected infection in critically ill patients. METHODS: PubMed and Embase were searched up to July 24th, 2019 to identify studies evaluating the diagnostic performance of FDG PET for finding infection focus in critically ill patients following the PRISMA guidelines. The bivariate mixed-effects model was used to pool the measure for diagnostic performance. Publication bias was evaluated by Deeks' method. RESULTS: A total of 4 studies with 87 patients were included. All the four studies evaluated FDG PET. Majority of the patients were either mechanically ventilated (76%) or shocked requiring vasopressors (61%). Test and transportation related adverse events were rare (2%). The summary sensitivity and specificity were 0.94 (95% CI, 0.79-0.99) and 0.66 (95% CI, 0.45-0.83), respectively. The AUC for summary ROC curve was 0.83. CONCLUSION: FDG PET was a very sensitive tool with acceptable specificity for detecting the origin of infection in critically ill patients. However, current available studies have limitation in evaluating safety issue. Further research should investigate both benefit and risk of doing this test for this group of vulnerable patients.

Treatment for Mycobacterium abscessus complex-lung disease.

Nontuberculous mycobacterial infections and colonization are becoming more prevalent worldwide. Mycobacterium abscessus complex (MABC) is one of the predominant pathogens capable of a wide spectrum of infections, with 50% of infections involving the lungs. The decision to commence treatment is determined according to the severity of the disease, risk of progressive disease, presence of comorbidities, and goals of treatment. MABC is resistant to standard antituberculous agents and has variable drug susceptibility across different geographical locations, therefore, antibiotic susceptibility testing of all clinically significant isolates is crucial for selecting a treatment strategy. Pulmonary infections due to MABC is difficult to cure using the currently recommended regimens from the American Thoracic Society and British Thoracic Society. Macrolides are the cornerstone of treatment, but the efficacy of macrolide-based chemotherapy may be compromised by resistance. Despite the introduction of new drugs for treatment, treatment outcomes remain unsatisfactory. The combination of surgical resection of limited lung disease regions with a multidrug, macrolide-based therapy offers the optimal chance of achieving clinical cure of the disease. This review focuses on medical treatment of MABC-lung disease and the efficacy of new agents, such as clofazimine, amikacin inhalation therapy, tigecycline and linezolid, for treating MABC-lung disease.

Ergonomics Analysis for Subjective and Objective Fatigue Between Laparoscopic and Robotic Surgical Skills Practice Among Surgeons.

Introduction. Our aim was to determine how self-reported and objectively measured fatigue of upper limb differ between laparoscopic and robotic surgical training environments. Methods. Surgeons at the 2016 SAGES Conference Learning Center and at our institution were enrolled. Two standardized surgical tasks (peg transfer [PT] and needle passing [NP]) were performed twice in each surgical skills practical environments: (1) laparoscopic training-box environment (Fundamentals of Laparoscopic Surgery [FLS]) and (2) Mimic dV-trainer (MIMIC). Muscle activation of upper trapezius (UT), anterior deltoid (AD), flexor carpi radialis, and extensor digitorum were recorded using surface electromyography (EMG; Trigno, Delsys, Inc, Natick, MA). Subjective fatigue was self-reported using Piper Fatigue Scale-12. Analysis was done using SPSS v25.0, α = .05. Results. Demographics were similar between FLS (N = 14) and MIMIC (N = 12). For PT, MIMIC had a significant increase in EMGRMS of UT (P < .001) and AD (P < .001). Conversely, FLS led to significant decreased muscle fatigue in UT (P = .015). For NP, MIMIC had a significant increase in EMGRMS for UT (P = .034) and AD (P = .031), but FLS induced more muscle fatigue for AD (P = .004). There was significant decrease in self-reported fatigue after performing FLS tasks (P = .030) but not after MIMIC (P = .663). Conclusion. Our results showed that practice with MIMIC resulted in greater activation of shoulder muscles, while FLS caused more significant muscle fatigue in the same muscles. This could be due to ergonomic disadvantages and nonoptimal ergonomic settings. Further studies are needed to understand the optimal ergonomics and its impact on fatigue and muscle activation during use of both the FLS and MIMIC training systems.

Improved diagnostic accuracy of thallium-201 myocardial perfusion single-photon emission computed tomography with CT attenuation correction.

BACKGROUND: The benefits of attenuation correction (AC) in technetium-99m myocardial perfusion imaging (MPI) have been well established. However, the value of thallium (Tl-201) AC and routine computed tomography AC (CTAC) were less well established. The aims of this study were to evaluate the diagnostic performance of thallium (Tl-201) MPI with additional CTAC and to determine which participants would benefit most. METHODS AND RESULTS: A total of 108 consecutive patients who underwent Tl-201 MPI and received coronary angiography within 3 months were enrolled. Diagnostic performance was determined by sensitivity, specificity, and receiver operating characteristic curve analysis. Subgroup analyses were performed using gender and obesity. CTAC improved the area under the curve (0.84 vs. 0.77, P = 0.037 at patient level), primarily due to a significant improvement in specificity (0.78 vs. 0.57, P = 0.013) and no significant difference in sensitivity (0.79 vs. 0.82, P = 0.75). In subgroup analysis, CTAC was most helpful in obese subjects, men, and especially right coronary artery lesions. CONCLUSIONS: CTAC significantly improved diagnostic performance primarily by increasing the specificity, and the improvements were significantly greater in obese patients and male patients. These findings suggest that CTAC should be applied to Tl-201 MPI as routine clinical practice.

Ergonomics of minimally invasive surgery: an analysis of muscle effort and fatigue in the operating room between laparoscopic and robotic surgery.

BACKGROUND: Our aim was to determine how objectively-measured and self-reported muscle effort and fatigue of the upper-limb differ between surgeons performing laparoscopic (LAP) and robotic-assisted (ROBOT) surgeries. METHODS: Surgeons performing LAP or ROBOT procedures at a single-institution were enrolled. Objective muscle activation and self-reported fatigue were evaluated, and comparisons were made between approaches. Muscle activation of the upper trapezius (UT), anterior deltoid (AD), flexor carpi radialis (FCR), and extensor digitorum (ED) were recorded during the surgical procedure using Trigno wireless surface electromyography (EMG). The maximal voluntary contraction (MVC) was obtained to normalize root-mean-square muscle activation as %MVCRMS. The median frequency (MDF) was calculated to assess muscle fatigue. Each surgeon also completed the validated Piper Fatigue Scale-12 (PFH-12) before and after the procedure for self-perceived fatigue assessment. Statistical analysis was done using SAS/STAT software, with α = 0.05. RESULTS: 28 surgeries were recorded (LAP: N = 18, ROBOT: N = 10). EMG analysis revealed the ROBOT group had a higher muscle activation than LAP for UT (37.7 vs. 25.5, p = 0.003), AD (8.9 vs. 6.3, p = 0.027), and FCR (14.4 vs. 10.9, p = 0.019). Conversely, LAP required more effort for the ED, represented by a significantly lower MDF compared to the ROBOT group (91.2 ± 1.5 Hz vs. 102.8 ± 1.5 Hz, p < 0.001). Survey analysis revealed no differences in self-reported fatigue before and after the surgery between approaches, p = 0.869. CONCLUSIONS: Our analysis revealed surgeons show similar fatigue levels performing the first case of the day using either robotic or LAP surgery. Surgeons performing LAP surgery had more fatigue in the forearm, robotic surgery required more shoulder and neck use, but neither was superior. Neither technique produced significant overall fatigue on survey. Long-term selective use of these different muscles could be correlated with different patterns of injury. Future studies are needed to fully understand long-term implications of prolonged surgery on occupational injury.

Transient activation of PKC results in long-lasting detrimental effects on systolic [Ca2+]i in cardiomyocytes by altering actin cytoskeletal dynamics and T-tubule integrity.

AIMS: Protein kinase C (PKC) isozymes contribute to the development of heart failure through dysregulation of Ca2+ handling properties and disruption of contractile function in cardiomyocytes. However, the mechanisms by which PKC activation leads to Ca2+ dysfunction are incompletely understood. METHODS AND RESULTS: Shortly upon ventricular pressure overload in mice, we detected transient PKC activation that was associated with pulsed actin cytoskeletal rearrangement. In cultured cardiomyocytes, transient activation of PKC promoted long-term deleterious effects on the integrity of the transverse (T)- tubule system, resulting in a significant decrease in the amplitude and increase in the rising kinetics of Ca2+ transients. Treatment with a PKCα/ß inhibitor restored the synchronization of Ca2+ transients and maintained T-tubule integrity in cultured cardiomyocytes. Supporting these data, PKCα/ß inhibition protected against T-tubule remodeling and cardiac dysfunction in a mouse model of pressure overload-induced heart failure. Mechanistically, transient activation of PKC resulted in biphasic actin cytoskeletal rearrangement, consistent with in vivo observations in the pressure overloaded mouse model. Transient inhibition of actin polymerization or depolymerization resulted in severe T-tubule damage, recapitulating the T-tubule damage induced by PKC activation. Moreover, inhibition of stretch activated channels (SAC) protected against T-tubule remodeling and E-C coupling dysfunction induced by transient PKC activation and actin cytoskeletal rearrangement. CONCLUSIONS: These data identify a key mechanistic link between transient PKC activation and long-term Ca2+ handling defects through PKC-induced actin cytoskeletal rearrangement and resultant T-tubule damage.