Drebrin is Required for Myosin-facilitated Actin Cytoskeletal Remodeling during Pulmonary Alveolar Development.

Alveolar septation increases gas-exchange surface area and requires coordinated cytoskeletal rearrangement in lung fibroblasts (LFs) to balance the demands of contraction and cell migration. We hypothesized that DBN (drebrin), a modulator of the actin cytoskeleton in neuronal dendrites, regulates the remodeling of the LF cytoskeleton. Using mice bearing a transgelin-Cre-targeted deletion of Dbn in pulmonary fibroblasts and pericytes, we examined alterations in alveolar septal outgrowth, LF spreading and migration, and actomyosin function. The alveolar surface area and number of alveoli were reduced, whereas alveolar ducts were enlarged, in mice bearing the dbn deletion (DBNΔ) compared with their littermates bearing only one dbn-Flox allele (control). Cultured DBNΔ LFs were deficient in their responses to substrate rigidity and migrated more slowly. Drebrin was abundant in the actin cortex and lamella, and the actin fiber orientation was less uniform in lamella of DBNΔ LFs, which limited the development of traction forces and altered focal adhesion dynamics. Actin fiber orientation is regulated by contractile NM2 (nonmuscle myosin-2) motors, which help arrange actin stress fibers into thick ventral actin stress fibers. Using fluorescence anisotropy, we observed regional intracellular differences in myosin regulatory light chain phosphorylation in control LFs that were altered by dbn deletion. Using perturbations to induce and then release stalling of NM2 on actin in LFs from both genotypes, we made predictions explaining how DBN interacts with actin and NM2. These studies provide new insight for diseases such as emphysema and pulmonary fibrosis, in which fibroblasts inappropriately respond to mechanical cues in their environment.

Transient low shear-stress preconditioning influences long-term endothelial traction and alignment under high shear flow.

Endothelial cells (ECs) within the vascular system encounter fluid shear stress (FSS). High, laminar FSS promotes vasodilation and anti-inflammatory responses, whereas low or disturbed FSS induces dysfunction and inflammation. However, the adaptation of endothelial cells (ECs) to dynamically changing FSS patterns remains underexplored. Here, by combining traction force microscopy with a custom flow chamber, we examined human umbilical vein endothelial cells adapting their traction during transitions from short-term low shear to long-term high shear stress. We discovered that the initial low FSS elevates the traction by only half of the amount in response to direct high FSS even after flow changes to high FSS. However, in the long term under high FSS, the flow started with low FSS triggers a substantial second rise in traction for over 10 h. In contrast, the flow started directly with high FSS results in a quick traction surge followed by a huge reduction below the baseline traction in <30 min. Importantly, we find that the orientation of traction vectors is steered by initial shear exposure. Using Granger causality analysis, we show that the traction that aligns in the flow direction under direct high FSS functionally causes cell alignment toward the flow direction. However, EC traction that orients perpendicular to the flow that starts with temporary low FSS functionally causes cell orientation perpendicular to the flow. Taken together, our findings elucidate the significant influence of initial short-term low FSS on lasting changes in endothelial traction that induces EC alignment.NEW & NOTEWORTHY In our study, we uncover that preconditioning with low shear stress yields enduring impacts on endothelial cell traction and orientation, persisting even after transitioning to high-shear conditions. Using Granger causality analysis, we demonstrate a functional link between the direction of cell traction and subsequent cellular alignment across varying shear environments.

Societal and community factors facilitating cultural adaptation and mental health of North Korean refugee women in South Korea.

North Korean (NK) refugee women face unique challenges in their acculturation process in South Korea (SK), often leading to higher rates of depression among them. This study uses the Multidimensional Individual Difference Acculturation (MIDA) model to examine the role of societal and local community factors in facilitating cultural adaptation and influencing mental health issues, such as depression, among NK refugee women. The study focuses on three predictors from the MIDA model: out-group social support, attachment to NK culture, and daily life experience of discrimination. Data from a sample of 212 NK refugee women in SK were analyzed using structural equation modeling. The findings highlight the crucial role of the social and community environment in attaining a balance between embracing a new culture and preserving one's connection to one's heritage culture. This balance is essential for promoting stable cultural adaptation, sound mental health, and overall well-being, so as to reduce the incidence of depression among NK refugee women. Based on the results, specific intervention strategies are proposed to support the acculturation journey of NK refugee women in SK.

Associations Between Tinnitus and Systemic Disease in Adolescents: Implications of Vitamin D Deficiency and Anaemia.

OBJECTIVES: Tinnitus is one of the irritating symptoms that should be addressed in adolescents. Since tinnitus affects mental health, it is important to treat it. However, identifying the cause of tinnitus is very challenging and the treatment strategies of tinnitus are controversial. The objective of this study was to identify the prevalence of tinnitus in adolescents and systemic diseases as risk factors of adolescent tinnitus to find evidence for new treatment strategies. MATERIALS AND METHODS: We extracted the subjects and data using the 5th Korea National Health and Nutrition Examination Survey from 2010 to 2012. One thousand five hundred ninety-three adolescents with bilateral normal tympanic membranes and availability of the results of physical, laboratory and audiological examinations, were selected. We evaluated their systemic diseases based on these results and assessed the association of tinnitus with demographic factors, systemic diseases and hearing levels. RESULTS: The prevalence of tinnitus in Korean adolescents was 21.7%. The hearing level was not associated with tinnitus. Tinnitus was significantly associated with age (p = 0.005), 25(OH)-D level (p = 0.007) and anaemia (p = 0.003). After controlling the other factors, age (p = 0.045), 25(OH)-D level (p = 0.041) and anaemia (p = 0.019) were independently related to tinnitus. CONCLUSION: Tinnitus in adolescents was significantly associated with age, vitamin D and anaemia. Physicians should consider the higher likelihood of these deficiencies or diseases in adolescent tinnitus patients. Additionally, recognizing these associations may be helpful in developing treatment strategies for adolescent tinnitus.

Developing and Validating the Senior Meaning in Life Evaluation (SMiLE) Scale.

The Senior Meaning in Life Evaluation scale encompasses not only older adults' personal motivation and growth but also the meaning for them in society and in their relationships: With this scale, we aimed to present their voices. A three-phase process was followed: The scale's items were developed empirically from interviews of older adults; exploratory factor analysis (EFA) was conducted to test convergent and concurrent validity; and finally, confirmatory factor analysis (CFA) was performed. EFA resulted in 18 items grouped into 4 factors (i.e., proactive on life, overcoming emptiness, acceptance in life, and social contribution), which was supported by the CFA.

Fully reconfigurable MEMS-based second-order coupled-resonator optical waveguide (CROW) with ultra-low tuning energy.

Integrated microring resonators are well suited for wavelength-filtering applications in optical signal processing, and cascaded microring resonators allow flexible filter design in coupled-resonator optical waveguide (CROW) configurations. However, the implementation of high-order cascaded microring resonators with high extinction ratios (ERs) remains challenging owing to stringent fabrication requirements and the need for precise resonator tunability. We present a fully integrated on-chip second-order CROW filter using silicon photonic microelectromechanical systems (MEMS) to adjust tunable directional couplers and a phase shifter using nanoscale mechanical out-of-plane waveguide displacement. The filter can be fully reconfigured with regard to both the ER and center wavelength. We experimentally demonstrated an ER exceeding 25 dB and continuous wavelength tuning across the full free spectral range of 0.123 nm for single microring resonator, and showed reconfigurability in second-order CROW by tuning the ER and resonant wavelength. The tuning energy for an individual silicon photonic MEMS phase shifter or tunable coupler is less than 22 pJ with sub-microwatt static power consumption, which is far better than conventional integrated phase shifters based on other physical modulation mechanisms.

Programmable MZI based on a silicon photonic MEMS-tunable delay line.

We report on a scalable and programmable integrated Mach-Zehnder interferometer (MZI) with a tunable free spectral range (FSR) and extinction ratio (ER). For the tunable path of the MZI, we designed and utilized a tunable delay line having high flexibility based on silicon photonic microelectromechanical systems (MEMS). By utilizing MEMS, the length of the delay line can be geometrically modified. In this way, there is no optical loss penalty other than the waveguide propagation loss as the number of tunable steps increases. Therefore, our device is more scalable in terms of optical loss than the previous approaches based on cascaded MZIs. In addition, the tuning energy required to reconfigure the length is only 8.46 pJ.

Low Power Coherent Ising Machine Based on Mechanical Kerr Nonlinearity.

Finding a reliable Ising machine for solving nondeterministic polynomial-class problems has attracted great attention in recent years, where an authentic system can be expanded with polynomial-scaled resources to find the ground state Ising Hamiltonian. In this Letter, we propose an extremely low power optomechanical coherent Ising machine based on a new enhanced symmetry breaking mechanism and highly nonlinear mechanical Kerr effect. The mechanical movement of an optomechanical actuator induced by the optical gradient force greatly increases the nonlinearity by a few orders and significantly reduces the power threshold using conventional structures capable of fabrication via photonic integrated circuit platforms. With the simple but strong bifurcation mechanism and remarkably low power requirement, our optomechanical spin model opens a path for chip-scale integration of large-size Ising machine implementations with great stability.

Investigating factors influencing post-operative growth in pre-pubertal children after adenotonsillectomy.

PURPOSE: To check the change in growth-for-age after adenotonsillectomy in pre-pubertal children and investigate the affecting factors. METHODS: Two hundred and six pediatric patients who underwent adenotonsillectomy by a single surgeon between January 2011 and December 2014 were included for the retrospective cohort study. The z-scores of height-, weight-, and body mass index (BMI)-for-age were measured before adenotonsillectomy and 1 year after the operation. The Korean version of the obstructive sleep apnea-18 questionnaire (OSA-18), symptom questionnaire, physical examinations, demographic data, and pre-operative z-scores were used to analyze the factors affecting z-score change. RESULTS: Among 206 pediatric patients, 167 patients were normal growth; 19 were undergrowth; and 20 were obese. After the operation, height, weight, and BMI z-scores all increased both in 167 normal-growth patients and 19 undergrowth patients (p value < 0.05). However, in 20 obese patients, only height z-score significantly increased (p value = 0.028). The multiple regression test showed that the sleep disturbance domain of OSA-18 was positively correlated with height z-score change (p value = 0.041), and age was negatively correlated with weight z-score change (p value = 0.016). Pre-operative BMI z-score was negatively correlated (p value = 0.019) and adenoid grade was positively correlated (p value = 0.023) with BMI z-score change. CONCLUSIONS: These findings suggest that adenotonsillectomy may positively affect growth in pre-pubertal children, without undesirable weight gain. Additionally, the sleep disturbance domain of OSA-18 may play a role in predicting post-operative height increase in pre-pubertal children.

Two-point coupling method to independently control coupling efficiency at different wavelengths.

To efficiently access light waves confined in a high-quality-factor (Q) microcavity over a wide spectral range, it is necessary to independently control coupling efficiency at different wavelengths. Here we suggest an approach to add a degree of freedom to control the coupling efficiency based on a two-point coupling geometry. By changing the phase difference between two paths connecting two coupling points, various combinations of coupling efficiencies at multiple wavelengths can be achieved. An analytic model describing the coupling property is derived and confirmed by experimental results. It is also shown that the coupling property can be modified by adjusting the effective refractive index difference between a waveguide and a resonator.

Supercontinuum generation in As2S3 waveguides fabricated without direct etching.

We report a supercontinuum generation (SCG) in a waveguide that spontaneously forms without an etching process during the deposition of a core material on a preformed ${\rm{Si}}{{\rm{O}}_2}$ substructure. The mechanism of dispersion control for this new, to the best of our knowledge, type of waveguide is analyzed by numerical simulation, which results in a design rule to achieve a target dispersion profile by adjusting the substructure geometry. SCG is experimentally demonstrated with a waveguide made of ${\rm{A}}{{\rm{s}}_2}{{\rm{S}}_3}$, chalcogenide glass, which has low material absorption over the mid-IR range. A dispersion-controlled waveguide with a length of 10 mm pumped with 77 pJ pulses at a telecommunication wavelength of 1560 nm resulted in a supercontinuum that extends by more than 1.5 octaves.

Associations between the working experiences at frontline of COVID-19 pandemic and mental health of Korean public health doctors.

BACKGROUND: Demographic, work environmental, and psychosocial features are associated with mental health of healthcare professionals at pandemic frontline. The current study aimed to find predictors of mental health for public health doctors from working experiences at frontline of COVID-19 pandemic. METHODS: With first-come and first-served manner, 350 public health doctors with experiences of work at COVID-19 frontline participated online survey on August 2020. Mental health was defined using the total scores of the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, the Perceived Stress Scale, and the Stanford Presenteeism Scale-6. Multivariate logistic regression models of mental health with lowest Akaike Information Criterion were determined among all combinations of working environments, perceived threats and satisfaction at frontline, and demographics that were significant (P < 0.05) in the univariate logistic regression. RESULTS: Perceived distress, lowered self-efficacy at work, anxiety, and depressive mood were reported by 45.7, 34.6, 11.4, and 15.1% of respondents, respectively. Predictors of poor mental health found in the multivariate logistic regression analyses were environmental (insufficient personal protective equipment, workplace of screening center, prolonged workhours) and psychosocial (fear of infection and death, social stigma and rejection) aspects of working experiences at frontline. Satisfaction of monetary compensation and proactive coping (acceptance and willingness to volunteer at frontline) were predictive of better mental health. CONCLUSIONS: Sufficient supply of personal protective equipment and training on infection prevention at frontline, proper workhours and satisfactory monetary compensation, and psychological supports are required for better mental health of public health doctors at frontline of COVID-19 pandemic.

Vimentin fibers orient traction stress.

The intermediate filament vimentin is required for cells to transition from the epithelial state to the mesenchymal state and migrate as single cells; however, little is known about the specific role of vimentin in the regulation of mesenchymal migration. Vimentin is known to have a significantly greater ability to resist stress without breaking in vitro compared with actin or microtubules, and also to increase cell elasticity in vivo. Therefore, we hypothesized that the presence of vimentin could support the anisotropic mechanical strain of single-cell migration. To study this, we fluorescently labeled vimentin with an mEmerald tag using TALEN genome editing. We observed vimentin architecture in migrating human foreskin fibroblasts and found that network organization varied from long, linear bundles, or "fibers," to shorter fragments with a mesh-like organization. We developed image analysis tools employing steerable filtering and iterative graph matching to characterize the fibers embedded in the surrounding mesh. Vimentin fibers were aligned with fibroblast branching and migration direction. The presence of the vimentin network was correlated with 10-fold slower local actin retrograde flow rates, as well as spatial homogenization of actin-based forces transmitted to the substrate. Vimentin fibers coaligned with and were required for the anisotropic orientation of traction stresses. These results indicate that the vimentin network acts as a load-bearing superstructure capable of integrating and reorienting actin-based forces. We propose that vimentin's role in cell motility is to govern the alignment of traction stresses that permit single-cell migration.

Multicast silicon photonic MEMS switches with gap-adjustable directional couplers.

We report on 4x20 silicon photonic MEMS switch that is capable of multicasting. The switch is built on passive optical crossbar network with gap-adjustable directional couplers. The switch has high on-off extinction ratio (59 dB), low insertion loss (< 4.0 dB), small footprint (1.2x4.5 mm2), and fast response (9.8 µs). The switching voltage is 9.6 V and 20 dB bandwidth is 31.5 nm. One-to-two and one-to-four multicast operations are demonstrated.

Silicon Photonic MEMS Phase-Shifter.

We present a design for an analog phase shifter based on Silicon Photonic MEMS technology. The operation principle is based on a two-step parallel plate electrostatic actuation mechanism to bring a vertically movable suspended tapered waveguide in a first step into proximity of the bus waveguide and to tune the phase of the propagating coupled mode in a second step by actuation of the suspended waveguide to tune the vertical gap. In the coupled state, the effective index of the optical supermode and the total accumulated phase delay can be varied by changing the vertical separation between the adiabatically tapered suspended and the fixed bus waveguides. Simulations predict that π phase shift can be achieved with an actuation voltage of 19 V, corresponding to a displacement of 19 nm. With an adiabatic coupler geometry, the optical signal can be coupled between the moving waveguide and the bus waveguide with low loss in a wide wavelength range from 1.5 µm to 1.6 µm keeping the average insertion loss below 0.3 dB.

Traction microscopy to identify force modulation in subresolution adhesions.

We present a reconstruction algorithm that resolves cellular tractions in diffraction-limited nascent adhesions (NAs). The enabling method is the introduction of sparsity regularization to the solution of the inverse problem, which suppresses noise without underestimating traction magnitude. We show that NAs transmit a distinguishable amount of traction and that NA maturation depends on traction growth rate. A software package implementing this numerical approach is provided.

Brief Report: Oxidative Stress Mediates Cardiomyocyte Apoptosis in a Human Model of Danon Disease and Heart Failure.

Danon disease is a familial cardiomyopathy associated with impaired autophagy due to mutations in the gene encoding lysosomal-associated membrane protein type 2 (LAMP-2). Emerging evidence has highlighted the importance of autophagy in regulating cardiomyocyte bioenergetics, function, and survival. However, the mechanisms responsible for cellular dysfunction and death in cardiomyocytes with impaired autophagic flux remain unclear. To investigate the molecular mechanisms responsible for Danon disease, we created induced pluripotent stem cells (iPSCs) from two patients with different LAMP-2 mutations. Danon iPSC-derived cardiomyocytes (iPSC-CMs) exhibited impaired autophagic flux and key features of heart failure such as increased cell size, increased expression of natriuretic peptides, and abnormal calcium handling compared to control iPSC-CMs. Additionally, Danon iPSC-CMs demonstrated excessive amounts of mitochondrial oxidative stress and apoptosis. Using the sulfhydryl antioxidant N-acetylcysteine to scavenge free radicals resulted in a significant reduction in apoptotic cell death in Danon iPSC-CMs. In summary, we have modeled Danon disease using human iPSC-CMs from patients with mutations in LAMP-2, allowing us to gain mechanistic insight into the pathogenesis of this disease. We demonstrate that LAMP-2 deficiency leads to an impairment in autophagic flux, which results in excessive oxidative stress, and subsequent cardiomyocyte apoptosis. Scavenging excessive free radicals with antioxidants may be beneficial for patients with Danon disease. In vivo studies will be necessary to validate this new treatment strategy.

Measuring the contractile forces of human induced pluripotent stem cell-derived cardiomyocytes with arrays of microposts.

Human stem cell-derived cardiomyocytes hold promise for heart repair, disease modeling, drug screening, and for studies of developmental biology. All of these applications can be improved by assessing the contractility of cardiomyocytes at the single cell level. We have developed an in vitro platform for assessing the contractile performance of stem cell-derived cardiomyocytes that is compatible with other common endpoints such as microscopy and molecular biology. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were seeded onto elastomeric micropost arrays in order to characterize the contractile force, velocity, and power produced by these cells. We assessed contractile function by tracking the deflection of microposts beneath an individual hiPSC-CM with optical microscopy. Immunofluorescent staining of these cells was employed to assess their spread area, nucleation, and sarcomeric structure on the microposts. Following seeding of hiPSC-CMs onto microposts coated with fibronectin, laminin, and collagen IV, we found that hiPSC-CMs on laminin coatings demonstrated higher attachment, spread area, and contractile velocity than those seeded on fibronectin or collagen IV coatings. Under optimized conditions, hiPSC-CMs spread to an area of approximately 420 µm2, generated systolic forces of approximately 15 nN/cell, showed contraction and relaxation rates of 1.74 µm/s and 1.46 µm/s, respectively, and had a peak contraction power of 29 fW. Thus, elastomeric micropost arrays can be used to study the contractile strength and kinetics of hiPSC-CMs. This system should facilitate studies of hiPSC-CM maturation, disease modeling, and drug screens as well as fundamental studies of human cardiac contraction.

Effects of Economic Status on Changes in Social Networks and Mental Health after Using Hearing Aids.

OBJECTIVES: Hearing impairment affects social networks and mental health. Hearing aids (HA) can improve these deficits. However, their effects might be affected by various factors such as economic status (ES). This study aimed to identify how ES could moderate the effects of HA on social networks, depressive mood, and cognition. METHODS: A prospective cohort for new HA users was established and classified into two groups based on their ES: a low ES group (LES group) and a medium to high ES group (MHES group). Audiological examination, Lubben social network scale-18 (LSNS-18), Short form of Geriatric Depression Score, Mini-Mental State Examination in the Korean version of the CERAD Assessment Packet, and surveys for satisfaction with HA were conducted before and at six months after wearing HA. RESULTS: Post-HA application LSNS-18 scores were not improved in the LES group whereas they revealed significant improvement in the MHES group (p = 0.003). The LES group showed lower LSNS-18 score (p = 0.020) and its change (p = 0.042) than the MHES group. Additionally, patients with depressive moods in the MHES group showed better improvements than those in the LES group (p = 0.048). The effects of wearing HA on cognition and satisfaction with HA were not significantly different between the two groups. CONCLUSIONS: HA did not improve social relationships and depressive moods in the LES group. Comprehensive and multidirectional support as well as hearing rehabilitation may be important for patients with LES. LEVEL OF EVIDENCE: 3 (Nonrandomized controlled cohort/follow-up study) Laryngoscope, 134:2387-2394, 2024.

Microalbuminuria and Functional Iron Deficiency are Risk Factors for Hearing Loss in Adolescents.

OBJECTIVES: Renal impairment and some systemic diseases are associated with hearing loss (HL) in adults. However, studies of these relationship in adolescents are rare. The objective of this study was to determine the association between HL and renal or systemic disease in adolescents. METHODS: Subjects were extracted from the 5th Korea National Health and Nutrition Examination Survey from 2011 to 2012. We included adolescents aged 10-19 years old with normal tympanic membrane and those who underwent a physical and laboratory examination and pure tone audiometry. HL, high-frequency hearing loss (HFHL), albuminuria, impaired glomerular filtration rate, hypertension, diabetes, and obesity were evaluated based on the data. RESULTS: Individuals with microalbuminruia (MIA) exhibited higher prevalence of HL (p = 0.003) and HFHL (p = 0.012) than those without MIA. The prevalence of HL and HFHL appeared to increase according to the severity of albuminuria. Additionally, individuals with HL or HFHL showed lower transferrin saturation (TSAT) than individuals without HL (p = 0.002) or HFHL (p = 0.001). And, HFHL was associated with lower ferritin levels (p = 0.017). HL and HFHL were related to MIA (p = 0.004 and p = 0.022, respectively) and TSAT (p = 0.005 and p = 0.011, respectively) after controlling other factors. CONCLUSION: MIA and TSAT level were independently associated with the HL and HFHL. Since MIA can be easily detected by dipstick test and urine analysis, hearing evaluations for individuals with MIA might be helpful to identify hearing impairments earlier in adolescents. LEVEL OF EVIDENCE: 3 (individual cross-sectional study) Laryngoscope, 134:3329-3334, 2024.