Optimizing the Amino Acid Sequence Enhances the Productivity and Bioefficacy of the RBP-Albumin Fusion Protein.

The significant growth of the global protein drug market, including fusion proteins, emphasizes the crucial role of optimizing amino acid sequences to enhance the productivity and bioefficacy. Among these fusion proteins, RBP-IIIA-IB, comprising retinol-binding protein in conjunction with the albumin domains, IIIA and IB, has displayed efficacy in alleviating liver fibrosis by inhibiting the activation of hepatic stellate cells (HSCs). This study aimed to address the issue of the low productivity in RBP-IIIA-IB. To induce structural changes, the linking sequence, EVDD, between domain IIIA and IB in RBP-IIIA-IB was modified to DGPG, AAAA, and GGPA. Among these, RBP-IIIA-AAAA-IB demonstrated an increase in yield (>4-fold) and a heightened inhibition of HSC activation. Furthermore, we identified amino acid residues that could form disulfide bonds when substituted with cysteine. Through the mutation of N453S-V480S in RBP-IIIA-AAAA-IB, the productivity further increased by over 9-fold, accompanied by an increase in anti-fibrotic activity. Overall, there was a more than 30-fold increase in the fusion protein's yield. These findings demonstrate the effectiveness of modifying linker sequences and introducing extra disulfide bonds to improve both the production yield and biological efficacy of fusion proteins.

Dysphagia Requiring Medical Attention in Parkinson's Disease: A Korean Population-Based Study.

BACKGROUND: Patients with Parkinson's disease (PD) experience both motor and non-motor symptoms, including dysphagia. Although PD is closely associated with dysphagia, the prevalence or risk of dysphagia in PD is unclear, especially in Asian countries. METHODS: The prevalence of PD and dysphagia with PD in the general population was analyzed using the Korean National Health Insurance Service (NHIS) database. The prevalence per 100,000 persons of PD and dysphagia with PD from 2006 to 2015 was analyzed in the general population aged ≥ 40 years. Patients newly diagnosed with PD between 2010 and 2015 were compared with those without PD. RESULTS: The prevalence of PD and dysphagia in patients with PD increased continuously during the study period and was highest in the ninth decade of life. The percentage of patients with dysphagia in patients with PD increased with age. Patients with PD showed an adjusted hazard ratio of 3.132 (2.955-3.320) for dysphagia compared to those without PD. CONCLUSION: This nationwide study showed increasing trends in the prevalence of PD and dysphagia among patients with PD in Korea between 2006 and 2015. The risk of dysphagia was three times higher in patients with PD than that in those without PD, highlighting the importance of providing particular attention.

White matter tracts involved in subcortical unilateral spatial neglect in subacute stroke.

Background: Unilateral spatial neglect (USN) is common and associated with poor motor and cognitive outcomes as well as impaired quality of life following stroke. Traditionally, the neural substrates underlying USN have been thought to be cortical areas, such as the posterior parietal cortex. However, patients with stroke involving only subcortical structures may also present with USN. While only a few studies have reported on USN in subcortical stroke, the involvement of white matter tracts related to brain networks of visuospatial attention is one possible explanation for subcortical neglect. Therefore, this study aimed to investigate which specific white matter tracts are neural substrates for USN in patients with subcortical stroke. Methods: Twenty-two patients with subcortical stroke without cortical involvement who were admitted to the Department of Rehabilitation Medicine at Seoul National University Bundang Hospital were retrospectively enrolled. Nine subjects were subclassified into a "USN(+)" group, as they had at least two positive results on three tests (the Schenkenberg line bisection test, Albert's test, and house drawing test) and a score of 1 or higher on the Catherine Bergego scale. The remaining 13 subjects without abnormalities on those tests were subclassified into the "USN(-)" group. Stroke lesions on MRI were manually drawn using MRIcron software. Lesion overlapping and atlas-based analyses of MRI images were conducted. The correlation was analyzed between the overlapped lesion volumes with white matter tracts and the severity of USN (in the Albert test and the Catherine Bergego scale). Results: Lesions were more widespread in the USN(+) group than in the USN(-) group, although their locations in the right hemisphere were similar. The atlas-based analyses identified that the right cingulum in the cingulate cortex, the temporal projection of the superior longitudinal fasciculus, and the forceps minor significantly overlapped with the lesions in the USN(+) group than in the USN(-) group. The score of the Catherine Bergego scale correlated with the volume of the involved white matter tracts. Conclusion: In this study, white matter tracts associated with USN were identified in patients with subcortical stroke without any cortical involvement. Our study results, along with previous findings on subcortical USN, support that USN may result from damage to white matter pathways.

Neuroprotective Effects and Therapeutic Potential of Transcorneal Electrical Stimulation for Depression.

Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.

Importance of Monitoring Physical Function for Quality of Life Assessments in Hematopoietic Stem Cell Transplantation Patients: A Prospective Cohort Study.

BACKGROUND/AIM: Physical function is known to decrease after hematopoietic stem cell transplantation (HSCT), with the most substantial impairment noted at 90 days post-transplantation. Little is known about the natural course of physical function during the acute post-transplant period preciously. The aim of the study was to monitor the changes in physical function through serial evaluations of the physical function, and identify the effect of physical function on QoL during the acute post-transplant period. PATIENTS AND METHODS: This prospective cohort study included 41 patients admitted for planned autologous or allogeneic HSCT. Physical impairment was evaluated with decrease in the de Morton Mobility Index (DEMMI) every week and defined as a DEMMI score of more than 2 points after HSCT. The outcome variables for QoL included visual analogue scale (VAS), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), and Zung Self-rating Depression Scale (SDS) at enrollment and discharge. RESULTS: Based on DEMMI scores, 24.40% of all HSCT patients showed physical impairment, for whom the DEMMI score showed an overall decrease during hospitalization with significant differences in scores at 1, 2, and 3 weeks after HSCT, between 1 week before and 3 weeks after HSCT, and between 1 and 3 weeks after HSCT. There was no significant difference of VAS between admission and discharge between the groups. Each functional subscale of EORTC QLQ-C30 differed significantly between the groups, with lower scores in the physical impairment group. There was only a significant difference in SDS at discharge between the groups. QoL pre-transplantation can be a predictive factor for physical impairment during the acute post-transplant period, which can be detected in the early period after HSCT. CONCLUSION: Patients during acute post-transplant period had physical impairment and QoL of pre-transplantation was considered a predictive factor for physical impairment. The physical impairment can be detected in the early period after HSCT. Therefore, monitoring of standardized functional outcome measures is important to prevent physical impairment following HSCT.

Comparison Between the Effectiveness of Complex Decongestive Therapy and Stellate Ganglion Block in Patients with Breast Cancer-Related Lymphedema: A Randomized Controlled Study.

BACKGROUND: Breast cancer-related lymphedema (BCRL) of the upper extremities often follows breast cancer treatment. Although complex decongestive therapy (CDT) is currently the standard treatment for BCRL, stellate ganglion block (SGB) has also been reported to be effective. OBJECTIVES: This study aimed to determine the effectiveness of SGB in the treatment of BCRL, and to assess the impact of the treatment on the quality of life (QoL) compared to CDT. STUDY DESIGN: A randomized controlled trial. SETTING: A single academic hospital, outpatient setting. METHODS: A total of 38 patients with BCRL were recruited. Patients were randomly divided into 2 groups. Patients enrolled in the CDT group underwent 10 sessions of CDT for 2 weeks, whereas patients in the SGB group received 3 consecutive SGBs every 2 weeks. Changes in circumference, volume, and bioimpedance in the upper extremity were measured at baseline and 2 weeks after treatment and compared between the 2 groups. EuroQol-5 dimensions (EQ-5D) and EuroQol visual analog scale (EQ VAS) for QoL and subjective improvement were monitored. RESULTS: In both groups, side-to-side difference of circumference after the treatment was decreased significantly from baseline (P < 0.05), and side-to-side difference of volume was reduced significantly in the SGB group (P < 0.05). No statistically significant difference was noted in the treatment effect between the 2 groups. Results of the EQ-5D, EQ VAS, and questionnaires regarding subjective symptoms administered at baseline and 2 weeks after each intervention revealed no statistically significant difference in the treatment effects between CDT and SGB. LIMITATIONS: Further long-term follow-up studies with a greater number of patients that include analysis according to the severity and duration of symptoms are needed. CONCLUSIONS: The results of this study suggest that SGB is an effective treatment for BCRL and may be considered as an alternative to CDT. KEY WORDS: Stellate ganglion block, complex decongestive therapy, breast cancer, lymphedema, breast cancer-related lymphedema, quality of life, bioimpedance, secondary lymphedema.

Lumbar synovial cyst with chronic viral hepatitis: A case series and literature review.

Cystic dilatation of synovial sheath, one of the targets of extra-hepatic manifestations associated with liver disease, is a main pathologic finding of lumbar synovial cyst (LSC). However, LSCs are not well documented in correlation with chronic viral hepatitis. In this case series, three patients with chronic viral hepatitis presented with radiating pain in the unilateral lower extremities. On magnetic resonance imaging of the lumbar spine, all had unilateral LSCs at the facet joint of the lumbar spine. Two did not have definite spinal instability at the LSC level. Ultimately, all three showed clinical improvements following epidural spine interventions.

Extravasation of the Contrast Material During Voiding Cystourethrography in a Chronic Spinal Cord Injury Patient: A Case Report.

Neurogenic bladder is common in most spinal cord injury patients. Voiding cystourethrography (VCUG) is recommended in these patients to detect urinary tract complications. However, rare but serious complications may occur during VCUG, although VCUG is generally safe. There are several case reports of bladder rupture occurring in pediatric patients. Here, we report the first case of iatrogenic bladder rupture in an adult spinal cord injury patient in Korea. Particularly, extravasation of contrast without manual instillation has hardly ever been reported. To the best of our knowledge, this is the first reported case of bladder rupture without manual instillation during VCUG. We report a case of a 59-year-old female with paraplegia due to tuberculous spondylitis who underwent VCUG as a part of routine evaluation of neurogenic bladder. Extravasation of the contrast media during VCUG developed as a complication and the patient recovered spontaneously without any intervention. Therefore, VCUG should be performed properly in chronic spinal cord injury patients.

Unusual Cause of Dysphagia in a Post-Stroke Patient.

Vallecular cysts are formed when the duct of a mucous gland or lingual tonsillar crypt is dilated owing to obstruction from inflammation, irritation, or trauma. Small cysts are usually asymptomatic; however, cyst growth results in dysphagia, odynophagia, and acute airway complications. As complete transoral laser excision of a vallecular cyst often results in cyst resolution and improved symptoms, proper diagnosis and management of vallecular lesions are important. We describe the evaluation and treatment of a 53-year-old man with a history of intracerebral hemorrhage in the left basal ganglia who presented with dysphagia caused by a vallecular cyst.

Larval chigger mites collected from small mammals in 3 provinces, Korea.

A total of 9,281 larval chigger mites were collected from small mammals captured at Hwaseong-gun, Gyeonggi-do (Province) (2,754 mites from 30 small mammals), Asan city, Chungcheongnam-do (3,358 mites from 48 mammals), and Jangseong-gun, Jeollanam-do (3,169 for 62 mammals) from April-November 2009 in the Republic of Korea (= Korea) and were identified to species. Leptotrombidium pallidum was the predominant species in Hwaseong (95.8%) and Asan (61.2%), while Leptotrombidium scutellare was the predominant species collected from Jangseong (80.1%). Overall, larval chigger mite indices decreased from April (27.3) to June (4.9), then increased in September (95.2) and to a high level in November (169.3). These data suggest that L. pallidum and L. scutellare are the primary vectors of scrub typhus throughout their range in Korea. While other species of larval chigger mites were also collected with some implications in the transmission of Orientia tsutsugamushi, they only accounted for 11.2% of all larval chigger mites collected from small mammals.