Developing a device for simultaneously investigating pivoting neuromuscular control and muscle properties toward a multi-axis rehabilitation.

Understanding the pivoting neuromuscular control of the lower limb and its associated muscle properties is critical for developing diagnostic and rehabilitation tools. However, to the best of our knowledge, a device that can evaluate these factors simultaneously remains lacking. To address this gap, a device that can investigate pivoting neuromuscular control and associated muscle properties was developed in this study. The proposed device consisted of a pivoting mechanism and height-adjustable chair with a brace interface. The device can control a footplate at various speeds to facilitate pivoting stretching and quantify neuromuscular control. Time-synchronized ultrasonographic images can be acquired simultaneously to quantify muscle properties during both active and passive pivoting movements. The muscle displacement, fascicle length/displacement, pennation angle, pivoting stiffness, and pivoting instability were investigated using the proposed device. Further, the feasibility of the device was demonstrated through a cross-sectional study with healthy subjects. The proposed device successfully quantified changes in muscle displacement during passive and active pivoting movements, pivoting stiffness during passive movements, and neuromuscular control during active movements. Therefore, the proposed device is expected to be used as a research and therapeutic tool for improving pivoting neuromuscular control and muscle functions and investigating the underlying mechanisms associated between muscle properties and joint movement in the transverse plane.

Stable nebulization and muco-trapping properties of regdanvimab/IN-006 support its development as a potent, dose-saving inhaled therapy for COVID-19.

The respiratory tract represents the key target for antiviral delivery in early interventions to prevent severe COVID-19. While neutralizing monoclonal antibodies (mAb) possess considerable efficacy, their current reliance on parenteral dosing necessitates very large doses and places a substantial burden on the healthcare system. In contrast, direct inhaled delivery of mAb therapeutics offers the convenience of self-dosing at home, as well as much more efficient mAb delivery to the respiratory tract. Here, building on our previous discovery of Fc-mucin interactions crosslinking viruses to mucins, we showed that regdanvimab, a potent neutralizing mAb already approved for COVID-19 in several countries, can effectively trap SARS-CoV-2 virus-like particles in fresh human airway mucus. IN-006, a reformulation of regdanvimab, was stably nebulized across a wide range of concentrations, with no loss of activity and no formation of aggregates. Finally, nebulized delivery of IN-006 resulted in 100-fold greater mAb levels in the lungs of rats compared to serum, in marked contrast to intravenously dosed mAbs. These results not only support our current efforts to evaluate the safety and efficacy of IN-006 in clinical trials, but more broadly substantiate nebulized delivery of human antiviral mAbs as a new paradigm in treating SARS-CoV-2 and other respiratory pathologies.

Linking Traumatic Childhood Experiences to the Physical Health of Korean Adolescents in Out-of-Home Care through Depression and Anxiety.

The main purpose of this study is to assess whether the physical health of Korean adolescents in out-of-home care is affected directly by traumatic childhood experiences and/or indirectly through depression and anxiety. Study participants are 460 adolescents who are included in the first and second wave of the Panel Study on Korean Children in Out-of-Home Care. The data are analyzed using structural equation modeling. Our structural model finds no direct effects of traumatic experiences on physical health. Among the two types of trauma experiences, namely, family instability and violence experiences, only violence experiences affect physical health indirectly through depression and anxiety. Based on the results, practice implications for Korean adolescents in care are discussed.

Crystal structure of Hop2-Mnd1 and mechanistic insights into its role in meiotic recombination.

In meiotic DNA recombination, the Hop2-Mnd1 complex promotes Dmc1-mediated single-stranded DNA (ssDNA) invasion into homologous chromosomes to form a synaptic complex by a yet-unclear mechanism. Here, the crystal structure of Hop2-Mnd1 reveals that it forms a curved rod-like structure consisting of three leucine zippers and two kinked junctions. One end of the rod is linked to two juxtaposed winged-helix domains, and the other end is capped by extra α-helices to form a helical bundle-like structure. Deletion analysis shows that the helical bundle-like structure is sufficient for interacting with the Dmc1-ssDNA nucleofilament, and molecular modeling suggests that the curved rod could be accommodated into the helical groove of the nucleofilament. Remarkably, the winged-helix domains are juxtaposed at fixed relative orientation, and their binding to DNA is likely to perturb the base pairing according to molecular simulations. These findings allow us to propose a model explaining how Hop2-Mnd1 juxtaposes Dmc1-bound ssDNA with distorted recipient double-stranded DNA and thus facilitates strand invasion.

The catheter tip position and effects of percutaneous epidural neuroplasty in patients with lumbar disc disease during 6-months of follow-up.

BACKGROUND: Percutaneous epidural neuroplasty (PEN) is a minimally invasive intervention designed to treat neck, back, and low back pain. The efficacy of lumbar PEN has been relatively well investigated, but clinical effectiveness according to catheter position has not yet been established. OBJECTIVE: The purpose of this study was to compare clinical outcomes between the ventral and dorsal positions of the catheter tip during lumbar PEN procedures using a retrospective review series. METHODS: A total of 303 patients with back pain from single-level lumbar disc disease with and without radiculopathy were included in this study. In all patients, an attempt was made to place the catheter tip in the ventral position to maximize theoretical clinical improvement; however, several catheters failed to reach the desired position. Patients were assigned to 2 groups after lumbar PEN procedures were completed: those with catheters in the ventral position (Ventral group) and those with catheters in the dorsal position (Dorsal group). Clinical outcomes were assessed according to the Visual Analog Scale (VAS) score for back pain and leg pain at 0, 1, 3, and 6 months after treatment. RESULTS: The only demographic difference observed between the 2 groups (Ventral and Dorsal groups) was an elongated symptom duration in the Dorsal group compared to the Ventral group (16.1 vs. 9.4 months, P = 0.013). The VAS (back) scores during the follow-up period (1, 3, and 6 months) were similar between the 2 groups. In one area of the VAS scoring (leg), the Ventral group showed a similar effect at postoperative one month compared to the Dorsal group, but significantly improved at postoperative 3 and 6 months (1.3 and 0.9 in ventral group, and 1.9 and 1.4 in dorsal group, respectively; P = 0.002 and 0.010). Odom's criteria were also significantly improved over 6 months in the Ventral group compared to the Dorsal group. LIMITATIONS: This study was a retrospective analysis with a relatively short follow-up duration was not a randomized, controlled study. Therefore, the clinical effects of the catheter position could be confounded by other variables. CONCLUSION: In this short-term follow-up study, the effects of lumbar PEN on VAS scores were different according to the position of the catheter tip in patients with single-level lumbar disc herniation. Better outcomes in the Ventral group may have been achieved by more localized treatment with a selective block in the epidural space closer to the dorsal root ganglion and ventral aspect of the nerve root.

Factors associated with perceived health among Korean adolescents.

This study examined the influences of personal, social, and environmental-structural factors on the perceived health of Korean adolescents. Using a two-stage generalized hierarchical logistic linear multilevel model, this study found that general high school enrollment, younger age, normal weight, and frequent exercise increased the likelihood of a positive self-perception of health. Higher levels of parental concern and quality of school life also contributed to the likelihood of students perceiving themselves as healthy. In contrast, psychological symptoms and negative self-esteem decreased the likelihood that students perceived themselves as healthy. The results provide implications for disease prevention and health promotion programs.

Influence of ABCB1 genetic polymorphisms on the pharmacokinetics of risperidone in healthy subjects with CYP2D6*10/*10.

BACKGROUND AND PURPOSE: The objective of this study was to investigate the combined influence of genetic polymorphisms in ABCB1 and CYP2D6 genes on risperidone pharmacokinetics. EXPERIMENTAL APPROACH: Seventy-two healthy Korean volunteers receiving a single oral dose of 2 mg risperidone were included in this study. KEY RESULTS: Significant differences were observed between the ABCB1 3435C>T genotypes for the pharmacokinetic parameters (peak serum concentration) of risperidone and the active moiety (risperidone and its main metabolite, 9-hydroxyrisperidone). There were no significant differences in the area under the serum concentration-time curves of risperidone and the active moiety among the ABCB1 2677G>T/A and 3435C>T genotypes. However, the peak serum concentration and area under the serum concentration-time curves were significantly different among the ABCB1 3435C>T genotypes in CYP2D6*10/*10. CONCLUSIONS AND IMPLICATIONS: These findings indicate that polymorphisms of ABCB1 3435C>T in individuals with CYP2D6*10/*10, which has low metabolic activity, could play an important role in the potential adverse effects or toxicity of risperidone.

The effect of MDR1 G2677T/A polymorphism on pharmacokinetics of gabapentin in healthy Korean subjects.

This study evaluated the relationship between the genetic polymorphism in the MDR1 (exon 21) genes and the pharmacokinetics of gabapentin (GBP) in healthy Korean subjects. The healthy Koreans were genotyped with respect to MDR1 (exon 21, 30 subjects) using polymerase chain reaction-based diagnostic testing. The pharmacokinetic profile of GBP was examined. A single oral dose of 300 mg GBP in a capsule was administered to the subjects and the blood samples were taken during a 24 h post-dose interval. The serum GBP concentration was measured using an HPLC-fluorescence detector system. There were no significant (P < 0.05) differences between the genotypes and pharmacokinetic parameters such as AUC(0-1h), AUC(0-1.5h), AUC(0-infinity), Cmax and t1/2. However, there was a trend toward higher values of the absorptive phase characterized by the AUC(0-1h) and AUC(0-1.5h) in 2677T/A subjects. In conclusion, this study suggests that GBP may be a weak substrate for the P-glycoprotein (P-gp) transporter.

Inter-rater reliability of the Illinois Structured Decision Support Protocol.

OBJECTIVE: The purpose of this study was to determine the level of inter-rater reliability of the Illinois Structured Decision Support Protocol by examining the level of Child Protective Services (CPS) caseworkers' agreement regarding state interventions. The Protocol was designed to guide CPS workers to consistent decisions related to the level of state intervention in child maltreatment cases. METHOD: Forty-one workers recruited from three CPS field offices in Illinois participated in this study by assessing three cases using the Illinois Structured Decision Support Protocol. The three cases were developed based on actual cases investigated by the agency. The kappa statistic was used to calculate the level of workers' agreement. RESULTS: The result showed a weak reliability (kappa=.29). Further analysis showed that workers identified a wide range of risk factors and differing levels of intervention for each identified risk factor even among the workers who made the same final decisions. CONCLUSIONS: Decision support protocols are developed to provide systematic structures for workers' decision-making. However, this study suggested that workers demonstrated a low level of agreement on such a protocol. Several suggestions for developing more reliable computerized protocols include: more specified inquiries with criteria to assess the range of risk for a factor, consideration of interactions among risk factors, assessment of family strengths, and having the final decision made by a computerized program.

Coexpression of BiP increased antithrombotic hirudin production in recombinant Saccharomyces cerevisiae.

In order to increase a production level of antithrombotic hirudin, BiP was simultaneously expressed in recombinant Saccharomyces cerevisiae strains carrying ten and 15 copies of the hirudin expression cassette integrated in the chromosome. Coexpression of BiP greatly enhanced both cell growth and hirudin production in recombinant S. cerevisiae. Maximum hirudin concentration of 36 mg l(-1) was obtained from batch culture of the ten copy-number transformant concomitantly harboring an episomal copy of the BiP gene under the control of the GAL1 promoter, which is corresponding to a 2.5-fold increase compared with the control strain carrying the genomic BiP gene only. The mean size of the recombinant yeast cells expressing the BiP gene remained at a relatively constant level compared with the control strains of which size increased after the onset of hirudin expression by the GAL10 promoter.