Adaptable Self-Assembly of a PEG Dendrimer-Coiled Coil Conjugate.

Self-assembly of designed molecules has enabled the construction of a variety of functional nanostructures. Specifically, adaptable self-assembly has demonstrated several advantageous features for smart materials. Here, we demonstrate that an α-helical coiled coil conjugated with a dendrimer can adapt to spatial restriction due to the strong steric repulsion between dendrimer chains. The adaptable transformation of a tetrameric coiled coil to a trimeric coiled coil can be confirmed using analytical ultracentrifugation upon conjugation of the dendrimer to the coiled coil-forming building block. Interestingly, circular dichroism spectroscopy analysis of the dendrimer conjugate revealed an unconventional trend: the multimerization of the coiled coil is inversely dependent on concentration. This result implies that the spatial crowding between the bulky dendritic chains is significantly stronger than that between linear chains, thereby affecting the overall assembly process. We further illustrated the application potential by decorating the surface of gold nanorods (AuNRs) with the adaptable coiled coil. The dendrimer-coiled coil peptide conjugate can be utilized to fabricate organic-inorganic nanohybrids with enhanced colloidal and thermal stabilities. This study demonstrates that the coiled coil can engage in the adaptable mode of self-assembly with the potential to form dynamic peptide-based materials.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations.

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10-20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3-152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Pilomatricoma on the Sole Following Wart Treatment.

Pilomatricoma is a benign skin tumor that arises from hair follicle stem cells. It typically presents in the facial region and rarely involves the palms and soles. A 15-year-old boy presented with a solitary tender nodule on the left sole. He had a history of plantar warts on the same site and had received multiple treatments including cryotherapy and intralesional bleomycin injection for nine months. Excisional biopsy was performed, and the specimen showed a well-demarcated mass in the deep dermis with basaloid cells undergoing abrupt keratinization. Ghost cells were seen with calcification. Based on these findings, he was diagnosed with pilomatricoma on the sole. We report a case of pilomatricoma, which developed on a site without hair follicles.

Cooperative Assembly of Self-Adjusting α-Helical Coiled Coils along the Length of an mRNA Chain to Form a Thermodynamically Stable Nanotube Carrier.

Although mRNA delivery technology is very promising, problems in safety and transport arise due to the intrinsically low thermodynamic stability of the current mRNA carriers. Considering that mRNAs are filamentous and a nanotube is one of the most thermodynamically stable shapes among nanoassemblies, a nanotube is one of the most stable supramolecular structures that can be assembled with mRNA. Here, we develop a nanotube-shaped filamentous mRNA delivery platform that shows exceptionally high thermodynamic stability. The key to the development of the mRNA nanotube is the design of self-adjusting supramolecular building blocks (SABs) that have two disparate properties, i.e., dynamic property and stiffness, in a single molecule. The counterbalance of the dynamic property and stiffness in SABs enables the coating of mRNA by winding its way through the flexible and irregular mRNA chain via cooperative interactions. SAB nanotubes with targeting ligands installed show a high uptake efficiency in mammalian cells and controllable gene expression behavior. Thus, the mRNA nanotube provides an enabling technology toward the development of safe and stable mRNA vaccines and therapeutics.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

This study presents the development of a ß-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded ß-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus. This stimulus-responsive property was translated into the effective capture and release of model multivalent biomaterials, hDM2-gold nanoparticle conjugates. Since numerous protein interactions are mediated by α-helical peptides, these results suggest that the ß-hairpin-based MT holds great potential to be utilized in various biomedical applications, such as protein interaction inhibition and cancer biomarker (e.g., circulating tumor cells and exosomes) detection.

Magnetic control of self-assembly and disassembly in organic materials.

Because organic molecules and materials are generally insensitive or weakly sensitive to magnetic fields, a certain means to enhance their magnetic responsiveness needs to be exploited. Here we show a strategy to amplify the magnetic responsiveness of self-assembled peptide nanostructures by synergistically combining the concepts of perfect α-helix and rod-coil supramolecular building blocks. Firstly, we develop a monomeric, nonpolar, and perfect α-helix (MNP-helix). Then, we employ the MNP-helix as the rod block of rod-coil amphiphiles (rod-coils) because rod-coils are well-suited for fabricating responsive assemblies. We show that the self-assembly processes of the designed rod-coils and disassembly of rod-coil/DNA complexes can be controlled in a magnetically responsive manner using the relatively weak magnetic field provided by the ordinary neodymium magnet [0.07 ~ 0.25 Tesla (T)]. These results demonstrate that magnetically responsive organic assemblies usable under practical conditions can be realized by using rod-coil supramolecular building blocks containing constructively organized diamagnetic moieties.

Structural control of self-assembled peptide nanostructures to develop peptide vesicles for photodynamic therapy of cancer.

Vesicles such as liposomes, polymersomes, and exosomes have been widely used as drug delivery carriers; however, peptide vesicles (peptidesomes) despite their potential utility are far less well developed. Peptidesomes are distinctive because peptides play dual roles as a self-assembly building block and a bioactive functional unit. In order for peptidesomes to become successful nanodrugs, the issues related to differences in nanostructural properties between in vitro and in vivo conditions should be addressed. Here, we delineate a multivariate approach to feedback control the structures of peptide building blocks, nanoparticle size, drug loading process, nanoparticle aggregation, cytotoxicity, cell targeting capability, endosome disruption function, protease resistance, and in vivo performance, which eventually enabled the successful development of a highly efficacious peptidesome for in vivo cancer therapy. This study lays the groundwork for the successful in vivo translation of peptide nanodrugs.

Cryolipolysis for abdominal subcutaneous fat reduction: A prospective, multicenter, single arm, clinical study.

Various treatment methods are used for noninvasive body contouring. To evaluate the efficacy and safety of a newly designed cryolipolysis device using a three-dimensional cooling method for abdominal fat reduction. Twenty-five participants with clinically apparent abdominal fat tissue participated in the study. The thickness of fat tissue below the umbilicus level was measured using a caliper at baseline and 12 weeks after the first treatment. The height of abdominal subcutaneous fat tissue on ultrasonography and participant satisfaction were assessed at every visit for 16 weeks. All adverse events (AEs) during the study period were recorded. p values <0.05 were considered statistically significant. Twenty-four participants completed this study; the mean BMI of participants was 29.34 ± 2.36 kg/m2 . The mean thickness of abdominal subcutaneous fat was significantly lower at 12 weeks (40.4 ± 6.8 mm, p < 0.001) than at baseline (49.3 ± 8.5 mm). Differences in the height of abdominal subcutaneous fat compared to that at baseline were 1.02 ± 0.41 cm (12 weeks, p < 0.001) and 1.13 ± 0.44 cm (16 weeks, p < 0.001). Rates of abdominal subcutaneous fat reduction at 12 and 16 weeks compared to that at baseline were 28.45% and 31.13%, respectively. The ratio of abdominal circumference to hip circumference at 12 and 16 weeks was significantly decreased compared to that at baseline. Most participants (95.8%) reported improvement in satisfaction scores at 16 weeks. There were no serious AEs during the entire study period. The study demonstrated the efficacy of a noninvasive cryolipolysis device using a three-dimensional cooling method for reducing abdominal subcutaneous fat.

Therapeutic Effects of New Pulsed-Type Microneedling Radiofrequency for Refractory Facial Pigmentary Disorders.

BACKGROUND: Numerous treatments for pigmentary disorders have been used with variable outcomes. Recently, a new radiofrequency (RF) device with minimal pulse duration has been introduced. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of a pulsed-type microneedling RF device for treatment of facial pigmentary disorders. METHODS: Forty-four patients diagnosed with facial melasma or Riehl melanosis received 5 treatments with RF at 2-week intervals, and evaluation was performed at each visits, including 4 and 8 weeks after the last treatment. Treatment outcomes were evaluated by investigator global assessment, patient global assessment score, and skin biophysical parameters of erythema index, melanin index (MI), and transepidermal water loss. Gene array and immunohistochemical staining including melan-A, Fontana silver, CD44, basic fibroblast growth factor (bFGF), and periodic acid-Schiff were performed. RESULTS: Most of the patients showed clinical improvement. Erythema index, MI, and transepidermal water loss decreased after the first treatment. Histopathologic examination showed decrease of melanin pigment, melanophages, and blood vessel proliferation but thickened basement membrane after treatment. Expression of CD44 and b-FGF was decreased after treatment. There were no serious adverse events reported during the study. CONCLUSION: Pulsed-type microneedling RF could be a treatment option for facial pigmentary disorders.

Complete recovery of herpes zoster radiculopathy based on electrodiagnostic study: A case report.

BACKGROUND: Herpes zoster is a painful infectious disease caused by the varicella zoster virus. Herpes zoster radiculopathy, which is a type of segmental zoster paresis, can complicate the disease and cause motor weakness. This complication should be considered when a patient with a rash complains of acute-onset motor weakness, and the diagnosis can be verified via electrodiagnostic study. CASE SUMMARY: A 64-year-old female with a history of asthma presented to the emergency department with stabbing pain, an itching sensation, and a rash on the right anterior shoulder that had begun 5 d prior. Physical examination revealed multiple erythematous grouped vesicles in the right C4-5 and T1 dermatome regions. Because herpes zoster was suspected, the patient immediately received intravenous acyclovir. On the third hospital day, she complained of motor weakness in the right upper extremity. Magnetic resonance imaging of the cervical spine revealed mild intervertebral disc herniation at C4-C5 without evidence of nerve root compression. On the 12th hospital day, electrodiagnostic study revealed right cervical radiculopathy, mainly in the C5/6 roots. Six months later, monoparesis resolved, and follow-up electrodiagnostic study was normal. CONCLUSION: This case emphasizes that clinicians should consider the possibility of post-herpetic paresis, such as herpes zoster radiculopathy, and that electrodiagnostic study is useful for diagnosis and follow-up.

The effects of the three-dimensional active trunk training exercise on trunk control ability, trunk muscle strength, and balance ability in sub-acute stroke patients: A randomized controlled pilot study.

BACKGROUND: Trunk control ability has been identified as an important early predictor of functional recovery after stroke. OBJECTIVE: Our study aimed to investigate the effects of three-dimensional active trunk training exercise on trunk control ability, trunk muscle strength, and balance ability in sub-acute stroke patients. METHODS: Twenty-four sub-acute stroke patients were randomly assigned to an experimental (n= 12) or control (n= 12) group. The experimental group (EG) performed three-dimensional active trunk training exercises using the Space Balance 3D system, while the control group (CG) performed only general trunk training exercises five times per week, for a total of three weeks. The Trunk Impairment Scale (TIS), trunk muscle strength, balance ability using the Space Balance 3D system, and Brunel Balance Assessment (BBA) scores were assessed before and after the intervention. RESULTS: Pre-to-post intervention improvement was noted in all outcome measures for both groups (p< 0.05). Post intervention, the TIS, trunk muscle strength, static balance, and BBA scores were significantly higher in the EG than those in the CG (p< 0.05). CONCLUSION: Our study suggests that the three-dimensional active trunk training exercise may be more effective compared to the general trunk training exercise in improving trunk control ability, trunk muscle strength, and balance ability in sub-acute stroke patients.

Characterization of the von Willebrand factor/factor VIII complex produced by a novel purification process.

Factor VIII (FVIII) is a blood coagulation protein that circulates as a complex with von Willebrand factor (vWF) in the plasma. In the survey of inhibitors in plasma product exposed toddlers (SIPPET) study, plasma-derived FVIII containing vWF was less immunogenic in hemophilia A patients than products with only high-purity FVIII only or recombinant FVIII. The  FVIII purified by the conventional purification process using anion-exchange (AEX) chromatography had a low vWF content. In this study, purified vWF was added to the purified FVIII to increase the vWF content. The purified vWF was recovered from the discarded washing solution of the AEX chromatography using cation-exchange (CEX) chromatography. The vWF/FVIII complex had an abundance of high molecular weight vWF similar to the normal plasma, and a low reactivity of FVIII inhibitors. Furthermore, its efficacy was observed in a mouse model of hemophilia A. Therefore, the vWF/FVIII complex produced by our new purification method could be an effective and less immunogenic therapeutic agent for the hemophilia A and von Willebrand disease.

Therapeutic effects of a new invasive pulsed-type bipolar radiofrequency for facial erythema associated with acne vulgaris and rosacea.

Facial erythema from rosacea and acne is one of the most common problems encountered in dermatologic clinics. Effective therapeutic interventions for persistent erythema, which can cause patients frustration and psychological distress, are needed. The aim of this study was to evaluate the efficacy and safety of an invasive short pulsed-type bipolar radiofrequency device (IPBRF) for the treatment of intractable facial erythema. Thirty-one patients who had been diagnosed with rosacea or acne vulgaris and combined erythema underwent at least two IPBRF treatment sessions (maximum: 5) at 2-week intervals. Treatment outcomes were evaluated by investigator global assessment (IGA) based on clinical photographs, patient global assessment (PGA) score, and skin biophysical parameters including erythema index (EI), melanin index (MI), and transepidermal water loss (TEWL). Most patients showed significant clinical improvement. IGA scores for erythema, pores and smoothness improved after treatment. PGA also showed a trend toward improvement. Mean EI was significantly improved after the second treatment compared to baseline, which maintained until the study period. MI and TEWL showed a tendency toward improvement. There were no serious adverse events reported during the study. IPBRF led to rapid clinical improvement in facial erythema associated with rosacea and acne vulgaris and could be an effective and safe treatment option.

The Effectiveness of Function-Focused Care Interventions in Nursing Homes: A Systematic Review.

BACKGROUND: Since the Omnibus Budget and Reconciliation Act was passed in South Korea in 1987, function-focused care (FFC) has been used in long-term care to achieve the highest possible levels of self-care and independence for older adults. However, many perceive nursing home residents with cognitive function impairments as having little restorative potential. PURPOSE: The purpose of this review is to report on evidence and strategies relating to FFC interventions in nursing home settings and to summarize the effects of FFC on the functional abilities of resident subgroups. METHODS: A literature review using EMBASE, MEDLINE, and Cumulative Index to Nursing and Allied Health Literature was conducted for articles published between January 1, 2000, and February 20, 2016. Twenty-two eligible studies were identified. Relevant data were extracted, and the results were synthesized into an integrated literature review. Study quality was appraised using the Cochrane Risk of Bias tool and the Risk of Bias Assessment tool for Non-randomized Studies. RESULTS: This review included 22 trials that were of moderate to high quality. Our systematic review confirmed the FFC interventions as integrated and dedicated processes; the five key strategies underpinning effective FFC interventions; and the effectiveness of FFC interventions on physical, psychosocial, and cognitive functions. The five key strategies underpinning FFC interventions included interactive learning for caregivers, the content of learning programs for caregivers, residents' preferences and interests, optimizing approaches according to residents' functional status, and the conceptual frameworks of FFC interventions. Most of the studies (n = 15) evaluated psychosocial functions and found significant improvements in aspects such as mood, affect, and behavioral problems. Likewise, the 13 studies assessing physical function found significant improvements in effectiveness in aspects such as movement, balance, and activities of daily living. Only four studies looked at cognitive function effectiveness, using measures such as place finding, verbal use, and memory. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Our review found scientific evidence that FFC interventions improve functional abilities across various levels of cognitive function in nursing homes. Nursing homes may employ effective strategies to maximize the effects of FFC interventions and use educational materials to teach caregivers to implement FFC interventions competently.

Anti-cariogenic Characteristics of Rubusoside.

Streptococcus mutans plays an important role in the development of dental caries in humans by synthesizing adhesive insoluble glucans from sucrose by mutansucrase activity. To explore the anti-cariogenic characteristics of rubusoside (Ru), a natural sweetener component in Rubus suavissimus S. Lee (Rosaceae), we investigated the inhibitory effect of Ru against the activity of mutansucrase and the growth of Streptococcus mutans. Ru (50 mM) showed 97% inhibitory activity against 0.1 U/mL mutansucrase of S. mutans with 500 mM sucrose. It showed competitive inhibition with a K i value of 1.1 ± 0.2 mM and IC50 of 2.3 mM. Its inhibition activity was due to hydrophobic and hydrogen bonding interactions based on molecular docking analysis. Ru inhibited the growth of S. mutans as a bacteriostatic agent, with MIC and MBC values of 6 mM and 8 mM, respectively. In addition, Ru showed synergistic anti-bacterial activity when it was combined with curcumin. Therefore, Ru is a natural anti-cariogenic agent with anti-mutansucrase activity and antimicrobial activity against S. mutans. ELECTRONIC SUPPLEMENTARY MATERIAL ESM: The online version of this article (doi: 10.1007/s12257-018-0408-0) contains supplementary material, which is available to authorized users.

Delayed Spontaneous Resorption of Lumbar Intervertebral Disc Herniation: A Case Report.

Background • Large intervertebral disc herniation is often managed with surgery, but it is not uncommon for spontaneous resorption of herniated disc material to occur. Although the majority of spontaneous disc resorption occurs in the acute phase, an unusual case of delayed intervertebral disc regression at 18 mo postonset is presented. Case Presentation • A 32-y-old female patient presented with acute low-back pain and pain in both legs a Korean medicine hospital specializing in spinal disorders. Massive intervertebral disc herniation was found on lumbar magnetic resonance imaging (MRI), and inguinal and genital pain and numbness was suggestive of risk of cauda equina syndrome. Although she was recommended for surgery, the patient steadfastly refused surgical intervention and continued to receive nonsurgical Korean medicine treatment. Imaging studies including computed tomography scans and MRIs were taken in consideration of possible spontaneous disc regression at 3 and 6 mo, and 1 y after onset of symptoms with no initial disc resorption. However, delayed spontaneous regression of most of the herniated disc material was observed at 18 mo, and the majority of pain symptoms and functional disability recovered up to 2 y postonset. Conclusions • Delayed intervertebral disc resorption was observed in a case of large disc herniation well past the acute phase, and there was noticeable time difference in resolution on MRI and subsequent improvement in pain and functional recovery.

Music-induced Mood Biases Decision Strategies during the Ultimatum Game.

Recently, an increasing attempt has been made to understand the influence of mood on socioeconomic decision-making. We tested in this study whether an unpleasant mood would lead to unfavorable decisions more frequently than a pleasant mood, and whether decisions under different moods can be explained in different ways. Healthy volunteers were assigned to either a pleasant or unpleasant mood group and listened to musical excerpts to induce pleasant or unpleasant mood. Both groups completed the ultimatum game as a responder with an unacquainted partner who was actually a confederate. The proposer's offers were made in six different ratios of split (1:9, 2:8, 3:7, 4:6, 5:5, 6:4) in a preprogramed manner unbeknownst to the participants. After the completion of the task as a responder, the participant rated subjectively perceived fairness and emotional feelings about each split of offer. The statistical results showed that the unpleasant mood group rejected unfair offers more often compared to the pleasant mood group. Self-reported ratings of perceived fairness and emotional feelings did not statistically differ between the two groups. Interestingly, however, only in the unpleasant mood group, rejection rates of unfair offers were negatively correlated with perceived fairness. Both the pleasant and unpleasant mood groups showed a negative correlation between rejection rates of unfair offers and self-reported happiness. These results suggest a possibility that different decision strategies operate under different mood during a socioeconomic exchange.