Sarcomere length-dependent Ca<Superscript>2+</Superscript> activation in skinned rabbit psoas muscle fibers: coordinated regulation of thin filament cooperative activation and passive force

In skeletal muscle, active force production varies as a function of sarcomere length (SL). It has been considered that this SL dependence results simply from a change in the overlap length between the thick and thin filaments. The purpose of this study was to provide a systematic understanding of the SL-dependent increase in Ca²⁺ sensitivity in skeletal muscle, by investigating how thin filament “on–off” switching and passive force are involved in the regulation. Rabbit psoas muscles were skinned, and active force measurements were taken at various Ca²⁺ concentrations with single fibers, in the short (2.0 and 2.4 μm) and long (2.4 and 2.8 μm) SL ranges. Despite the same magnitude of SL elongation, the SL-dependent increase in Ca²⁺ sensitivity was more pronounced in the long SL range. MgADP (3 mM) increased the rate of rise of active force and attenuated SL-dependent Ca²⁺ activation in both SL ranges. Conversely, inorganic phosphate (Pi, 20 mM) decreased the rate of rise of active force and enhanced SL-dependent Ca²⁺ activation in both SL ranges. Our analyses revealed that, in the absence and presence of MgADP or Pi, the magnitude of SL-dependent Ca²⁺ activation was (1) inversely correlated with the rate of rise of active force, and (2) in proportion to passive force. These findings suggest that the SL dependence of active force in skeletal muscle is regulated via thin filament “on–off” switching and titin (connectin)-based interfilament lattice spacing modulation in a coordinated fashion, in addition to the regulation via the filament overlap.     

Self-Transcendence Mediates the Relationship between Early Trauma and Fatal Methods of Suicide Attempts

BackgroundEarly trauma is known to be a risk factor of suicide-related behavior. On the other hand, people who attempt suicide using a fatal method are reported to be more likely to complete suicide. In this study, we assumed that early trauma affects an individual''s temperament and character and thereby increases the risk of a fatal method of suicide attempts.MethodsWe analyzed 92 people with a history of previous suicide attempts. We compared the Temperament and Character Inventory-Revised scores between the groups with and without early trauma, and between the groups with and without a history of suicide attempt using fatal methods through an analysis of covariance with age, sex, and presence of a psychiatric history as covariates. A mediation analysis was conducted of the relationship between early trauma and fatal methods of suicide attempt with self-transcendence as a mediator.ResultsHigher self-transcendence was reported in the fatal group (27.71 ± 13.78 vs. 20.97 ± 12.27, P = 0.010) and the early trauma group (28.05 ± 14.30 vs. 19.43 ± 10.73, P = 0.001), respectively. The mediation model showed that self-transcendence mediates the relationship between early trauma and fatal methods of suicide attempt. The 95% confidence intervals for the direct and indirect effect were (−0.559, 1.390) and (0.026, 0.947), respectively.ConclusionSelf-transcendence may mediate the relationship between early trauma and fatal methods of suicide attempt. Self-transcendence may be associated with unhealthy defenses and suicidal behavior for self-punishment and may constitute a marker of higher suicide risk.     

Risk Factors Predicting Severe Asthma Exacerbations in Adult Asthmatics: A Real-World Clinical Evidence

PurposeMinimizing the future risk of asthma exacerbation (AE) is one of the main goals of asthma management. We investigated prognostic factors for risk of severe AE (SAE) in a real-world clinical setting.MethodsThis is an observational study evaluating subjects who were diagnosed with asthma and treated with anti-asthmatic medications from January 1995 to June 2018. Risk factors for SAE were analyzed in 2 treatment periods (during the initial 2 years and the following 3–10 years of treatment) using the big data of electronic medical records.ResultsIn this study, 5,058 adult asthmatics were enrolled; 1,335 (28.64%) experienced ≥ 1 SAE during the initial 2 years of treatment. Female sex, higher peripheral eosinophil/basophil counts, and lower levels of forced expiratory volume in 1 second (FEV1; %) were factors predicting the risk of SAEs (P < 0.001 for all). Higher serum total immunoglobulin E levels increased the risk of SAEs among the patients having ≤ 2 SAEs (P = 0.025). Patients with more frequent SAEs during the initial 2 years of treatment had significantly higher risks of SAEs during the following years of treatment (P < 0.001, for all) (patients with ≥ 4 SAEs, odds ratio [OR], 29.147; those with 3 SAEs, OR, 14.819; those with 2 SAEs, OR, 9.867; those with 1 SAE, OR, 5.116), had higher maintenance doses of systemic steroids, and showed more gradual decline in FEV1 (%) and FEV1/forced vital capacity levels maintained during the following years of treatment (P < 0.001 for all).ConclusionsAsthmatics having risk factors for SAEs (female sex, higher peripheral eosinophil/basophil counts, and lower FEV1) should be strictly monitored to prevent future risk and improve clinical outcomes.     

Interaction Effects between COVID-19 Outbreak and Community Income Levels on Excess Mortality among Patients Visiting Emergency Departments

BackgroundThe objective of this study was to examine the effect of the coronavirus disease 2019 (COVID-19) outbreak on excess in-hospital mortality among patients who visited emergency departments (EDs) and to assess whether the excess mortality during the COVID-19 pandemic varies by community income level.MethodsThis is a cross-sectional study using the National Emergency Department Information System (NEDIS) database in Korea. The study population was defined as patients who visited all 402 EDs with medical conditions other than injuries between January 27 and May 31, 2020 (after-COVID) and for the corresponding time period in 2019 (before-COVID). The primary outcome was in-hospital mortality. The main exposure was the COVID-19 outbreak, and the interaction variable was county per capita income tax. We calculated the risk-adjusted in-hospital mortality rates by COVID-19 outbreak, as well as the difference-in-difference of risk-adjusted rates between the before-COVID and after-COVID groups according to the county income tax using a multilevel linear regression model with the interaction term.ResultsA total of 11,662,167 patients (6,765,717 in before-COVID and 4,896,450 in after-COVID) were included in the study with a 1.6% crude in-hospital mortality rate. The risk-adjusted mortality rate in the after-COVID group was higher than that in the before-COVID group (1.82% vs. 1.50%, difference: 0.31% [0.30 to 0.33]; adjusted odds ratio: 1.22 [1.18 to 1.25]). The excess in-hospital mortality rate of the after-COVID in the lowest quartile group of county income tax was significantly higher than that in the highest quartile group (difference-in-difference: 0.18% (0.14 to 0.23); P-for-interaction: < 0.01).ConclusionDuring the COVID-19 pandemic, there was excess in-hospital mortality among patients who visited EDs, and there were disparities in excess mortality depending on community socioeconomic positions.     

Effect of the C3a-Receptor Antagonist SB 290157 on Anti-OVA Polyclonal Antibody–Induced Arthritis

It was investigated whether the C3a-receptor antagonist (C3aRA) SB 290157 was involved in the suppression of anti-OVA pAb–induced arthritis because it is well known that anaphylatoxin C3a plays a crucial role in the development of an effective inflammatory response during complement activation. Anti-OVA pAb–induced arthritis was induced in DBA/1J mice by administration of anti-OVA pAb 0.5 h prior to intra-articular (i.a.) injection of OVA (0 h). Two peaks of joint swelling were observed at 0.5 and 3 h. The role of C3aRA in arthritis was investigated by injection of SB 290157 at concentrations of 10 and 30 mg/kg at 0 and 2 h. The antagonist was able to reduce joint swelling only at 3 h, and about 50% inhibition of joint swelling was observed with the concentration of 30 mg/kg. The C3 level was significantly decreased at 3 h compared with naïve mice showing complement consumption. Furthermore, the C3 activation was observed and increased corresponding to the graded concentration of anti-OVA pAb. The results also revealed that the C3aRA was able to reduce the expression of IL-1β in synovial tissue. Taken together, the results suggested that C3aRA may be effective in the inhibition of arthritis.     

Effect of the Heat-exposure on Peripheral Sudomotor Activity Including the Density of Active Sweat Glands and Single Sweat Gland Output

Tropical inhabitants are able to tolerate heat through permanent residence in hot and often humid tropical climates. The goal of this study was to clarify the peripheral mechanisms involved in thermal sweating pre and post exposure (heat-acclimatization over 10 days) by studying the sweating responses to acetylcholine (ACh), a primary neurotransmitter of sudomotor activity, in healthy subjects (n=12). Ten percent ACh was administered on the inner forearm skin for iontophoresis. Quantitative sudomotor axon reflex testing, after iontophoresis (2 mA for 5 min) with ACH, was performed to determine directly activated (DIR) and axon reflex-mediated (AXR) sweating during ACh iontophoresis. The sweat rate, activated sweat gland density, sweat gland output per single gland activated, as well as oral and skin temperature changes were measured. The post exposure activity had a short onset time (p<0.01), higher active sweat rate [(AXR (p<0.001) and DIR (p<0.001)], higher sweat output per gland (p<0.001) and higher transepidermal water loss (p<0.001) compared to the pre-exposure measurements. The activated sweat rate in the sudomotor activity increased the output for post-exposure compared to the pre-exposure measurements. The results suggested that post-exposure activity showed a higher active sweat gland output due to the combination of a higher AXR (DIR) sweat rate and a shorter onset time. Therefore, higher sudomotor responses to ACh receptors indicate accelerated sympathetic nerve responsiveness to ACh sensitivity by exposure to environmental conditions.     

Perfusion Imaging of the Brain Using Z-Score and Dynamic Images Obtained by Subtracting Images from before and after Contrast Injection

Objective

The aim of this study was to examine the feasibility of perfusion imaging of the brain using the Z-score and subtraction dynamic images obtained from susceptibility contrast MR images.

Materials and Methods

Five patients, each with a normal MRI, Moya-moya, a middle cerebral artery occlusion, post-trauma syndrome, and a metastatic brain tumor, were selected for a presentation. A susceptibility-contrast echo-planar image after a routine MRI was taken as the source image with a rapid manual injection of 0.1 mmol/kg of Gd-DTPA. The inflow and washout patterns were observed from the time-signal intensity curve of the serial scans using the standard program of an MRI machine. The repeated Z-score images of the peak and late phases were made using the threshold Z-score values between 1.4 and 2.0 in four to five studies of the pre-contrast, peak, and late phases. Dynamic subtraction images were produced by subtracting sequential post-contrast images from a pre-contrast image and coloring these images using a pseudocolor mapping method.

Results

In the diseases with perfusion abnormalities, the Z-score images revealed information about the degree of perfusion during the peak and late phases. However, the quality varied with the Z-score threshold and the studies selected in a group. The dynamic subtraction images were of sufficient quality with no background noise and more clearly illustrated the temporal changes in perfusion and delayed perfusion.

Conclusion

The Z-scores and dynamic subtraction images illustrated the degree of perfusion and sequential changes in the pattern of perfusion, respectively. These images can be used as a new complimentary method for observing the perfusion patterns in brain diseases.     

Non-Contiguous Spinal Injury in Cervical Spinal Trauma: Evaluation with Cervical Spine MRI

Objective

We wished to evaluate the incidence of non-contiguous spinal injury in the cervicothoracic junction (CTJ) or the upper thoracic spines on cervical spinal MR images in the patients with cervical spinal injuries.

Materials and Methods

Seventy-five cervical spine MR imagings for acute cervical spinal injury were retrospectively reviewed (58 men and 17 women, mean age: 35.3, range: 18-81 years). They were divided into three groups based on the mechanism of injury; axial compression, hyperflexion or hyperextension injury, according to the findings on the MR and CT images. On cervical spine MR images, we evaluated the presence of non-contiguous spinal injury in the CTJ or upper thoracic spine with regard to the presence of marrow contusion or fracture, ligament injury, traumatic disc herniation and spinal cord injury.

Results

Twenty-one cases (28%) showed CTJ or upper thoracic spinal injuries (C7-T5) on cervical spinal MR images that were separated from the cervical spinal injuries. Seven of 21 cases revealed overt fractures in the CTJs or upper thoracic spines. Ligament injury in these regions was found in three cases. Traumatic disc herniation and spinal cord injury in these regions were shown in one and two cases, respectively. The incidence of the non-contiguous spinal injuries in CTJ or upper thoracic spines was higher in the axial compression injury group (35.3%) than in the hyperflexion injury group (26.9%) or the hyperextension (25%) injury group. However, there was no statistical significance (p > 0.05).

Conclusion

Cervical spinal MR revealed non-contiguous CTJ or upper thoracic spinal injuries in 28% of the patients with cervical spinal injury. The mechanism of cervical spinal injury did not significantly affect the incidence of the non-contiguous CTJ or upper thoracic spinal injury.