A Printable Magnetic-Responsive Iron Oxide Nanoparticle (ION)-Gelatin Methacryloyl (GelMA) Ink for Soft Bioactuator/Robot Applications.

The features or actuation behaviors of nature's creatures provide concepts for the development of biomimetic soft bioactuators/robots with stimuli-responsive capabilities, design convenience, and environmental adaptivity in various fields. Mimosa pudica is a mechanically responsive plant that can convert pressure to the motion of leaves. When the leaves receive pressure, the occurrence of asymmetric turgor in the extensor and flexor sides of the pulvinus from redistributing the water in the pulvinus causes the bending of the pulvinus. Inspired by the actuation of Mimosa pudica, designing soft bioactuators can convert external stimulations to driving forces for the actuation of constructs which has been receiving increased attention and has potential applications in many fields. 4D printing technology has emerged as a new strategy for creating versatile soft bioactuators/robots by integrating printing technologies with stimuli-responsive materials. In this study, we developed a hybrid ink by combining gelatin methacryloyl (GelMA) polymers with iron oxide nanoparticles (IONs). This hybrid ION-GelMA ink exhibits tunable rheology, controllable mechanical properties, magnetic-responsive behaviors, and printability by integrating the internal metal ion-polymeric chain interactions and photo-crosslinking chemistries. This design offers the inks a dual crosslink mechanism combining the advantages of photocrosslinking and ionic crosslinking to rapidly form the construct within 60 s of UV exposure time. In addition, the magnetic-responsive actuation of ION-GelMA constructs can be regulated by different ION concentrations (0-10%). Furthermore, we used the ION-GelMA inks to fabricate a Mimosa pudica-like soft bioactuator through a mold casting method and a direct-ink-writing (DIW) printing technology. Obviously, the pinnule leaf structure of printed constructs presents a continuous reversible shape transformation in an air phase without any liquid as a medium, which can mimic the motion characteristics of natural creatures. At the same time, compared to the model casting process, the DIW printed bioactuators show a more refined and biomimetic transformation shape that closely resembles the movement of the pinnule leaf of Mimosa pudica in response to stimulation. Overall, this study indicates the proof of concept and the potential prospect of magnetic-responsive ION-GelMA inks for the rapid prototyping of biomimetic soft bioactuators/robots with untethered non-contact magneto-actuations.

The Bacterial Markers of Identification of Invasive CovR/CovS-Inactivated Group A Streptococcus.

Necrotizing fasciitis is a severe infectious disease that results in significant mortality. Streptococcus pyogenes (group A Streptococcus, GAS) is one of the most common bacterial pathogens of monomicrobial necrotizing fasciitis. The early diagnosis of necrotizing fasciitis is crucial; however, the typical cutaneous manifestations are not always presented in patients with GAS necrotizing fasciitis, which would lead to miss- or delayed diagnosis. GAS with spontaneous inactivating mutations in the CovR/CovS two-component regulatory system is significantly associated with destructive diseases such as necrotizing fasciitis and toxic shock syndrome; however, no specific marker has been used to identify these invasive clinical isolates. This study evaluated the sensitivity and specificity of using CovR/CovS-controlled phenotypes to identify CovR/CovS-inactivated isolates. Results showed that the increase of hyaluronic acid capsule production and streptolysin O expression were not consistently presented in CovS-inactivated clinical isolates. The repression of SpeB is the phenotype with 100% sensitivity of identifying in CovS-inactivated isolates among 61 clinical isolates. Nonetheless, this phenotype failed to distinguish RopB-inactivated isolates from CovS-inactivated isolates and cannot be utilized to identify CovR-inactivated mutant and RocA (Regulator of Cov)-inactivated isolates. In this study, we identified and verified that PepO, the endopeptidase which regulates SpeB expression through degrading SpeB-inducing quorum-sensing peptide, was a bacterial marker to identify isolates with defects in the CovR/CovS pathway. These results also inform the potential strategy of developing rapid detection methods to identify invasive GAS variants during infection. IMPORTANCE Necrotizing fasciitis is rapidly progressive and life-threatening; if the initial diagnosis is delayed, deep soft tissue infection can progress to massive tissue destruction and toxic shock syndrome. Group A Streptococcus (GAS) with inactivated mutations in the CovR/CovS two-component regulatory system are related to necrotizing fasciitis and toxic shock syndrome; however, no bacterial marker is available to identify these invasive clinical isolates. Inactivation of CovR/CovS resulted in the increased expression of endopeptidase PepO. Our study showed that the upregulation of PepO mediates a decrease in SpeB-inducing peptide (SIP) in the covR mutant, indicating that CovR/CovS modulates SIP-dependent quorum-sensing activity through PepO. Importantly, the sensitivity and specificity of utilizing PepO to identify clinical isolates with defects in the CovR/CovS pathway, including its upstream RocA regulator, were 100%. Our results suggest that identification of invasive GAS by PepO may be a strategy for preventing severe manifestation or poor prognosis after GAS infection.

Postoperative vascular event prediction using angiography and ultrasonography in patients with Moyamoya disease.

OBJECTIVE: Indirect revascularization surgery reduce the risk of recurrent vascular events in patients with moyamoya disease (MMD), but the roles of postoperative angiography and ultrasonography in predicting these events remain unclear. METHODS: This prospective study enrolled patients with MMD who would undergo their first unilateral indirect revascularization surgery. They received preoperative and postoperative ultrasound examination at 1, 3, and 6 months and conventional cerebral angiography. On ultrasonography, postoperative emerging flow (PEF) in an intracranial artery was defined as emerging flow postoperatively with absence of flow preoperatively. Predictors of vascular event frequency reduction were identified from angiographic and ultrasonographic parameters. RESULTS: In total, 52 patients (including 24 pediatric and 24 male patients), who underwent 52 preoperative and 82 postoperative ultrasound examinations, were enrolled. Significant postoperative changes were noted in all the ultrasonographic parameters of ipsilateral superficial temporal artery (STA) and the end-diastolic velocity and flow volume in contralateral STA. During a median follow-up of 5.3 years, indirect revascularization surgery significantly reduced the occurrence of ipsilateral vascular events. Predictors of vascular event frequency reduction included Matsushima grade A or B on the ipsilateral side on angiography (odds ratio [OR] = 22.00, P = 0.002) and lower resistance index (RI) in ipsilateral STA (OR = 0.0001, P = 0.012) but no PEF pattern in ipsilateral middle cerebral artery (OR = 0.14, P = 0.029) on ultrasonography performed within 6 months. CONCLUSIONS: Reduction of long-term vascular event frequency probably can be predicted through postoperative angiography and ultrasonography within 6 months after indirect revascularization surgery.

Mismatch negativity to different deviant changes in autism spectrum disorders: A meta-analysis.

OBJECTIVE: Mismatch negativity (MMN) has been continuously used to evaluate the functional integrity of central auditory processing. However, it still remains inconclusive whether patients with autism spectrum disorder (ASD) demonstrate reduced MMN responses in all deviant types. METHODS: To reconcile the previous controversial findings, we performed a meta-analysis of peer-reviewed MMN articles concerning ASD. The potential moderators regarding different deviant types, diagnosis, and age on the effect sizes (Hedges' g) were also assessed. RESULTS: Compared to the controls, ASD patients showed reduced MMN amplitudes (g = -0.37, p = 0.001) and prolonged latencies (g = -0.33, p = 0.041) in response to speech-sound deviants. Children/adolescents with ASD manifested reduced MMN amplitudes in response to tone-duration deviants (g = -0.46, p = 0.014). Furthermore, the results showed significantly shortened MMN latencies to tone-frequency deviants in patients with autism (g = 0.29, p = 0.038) and, in contrast, prolonged MMN latencies (g = -0.74, p = 0.001) in patients with Asperger syndrome. CONCLUSION: MMN deficits are robust in ASD patients, suggesting an altered central ability in auditory discrimination. SIGNIFICANCE: MMN alterations were displayed in different profiles with respect to frequency, duration and phoneme changes.

Real-world cost-effectiveness of drug-eluting stents vs. bare-metal stents for coronary heart disease-A five-year follow-up study.

OBJECTIVE: To evaluate the cost-effectiveness of using drugeluting stents (DES) compared to bare-metal stents (BMS) for coronary heart disease (CHD). DATA SOURCES/STUDY SETTING: Data were obtained from the National Health Insurance Longitudinal Health Insurance Database, which contains claims data for 1,000,000 beneficiaries. The data were randomly sampled from all beneficiaries. STUDY DESIGN: A retrospective claims data analysis. DATA COLLECTION/EXTRACTION METHODS: Patients with stable coronary heart disease who underwent coronary stent implantation from 2007 to 2008 were recruited and followed to the end of 2013. After a 2:1 propensity score matched by gender, age, stent number, and the Charlson comorbidity index (CCI), 852 patients with 568 stents in the BMS group and 284 stents in the DES group were included. The cumulative medical costs for both matched groups were estimated with the Kaplan-Meier Sample Average (KMSA), and then the incremental cost-effectiveness ratio (ICER) was estimated. PRINCIPAL FINDINGS: The ICER of DES vs. BMS was NT$ 663,000 per cardiovascular death averted and NT$ 238,394 per cardiovascular death or coronary event averted in five years from the insurer perspective. CONCLUSION: Percutaneous coronary intervention (PCI) with DES was a more cost-effective strategy than PCI with BMS for CHD patients during the five-year follow-up.

Comparison of Clinical Outcomes in Patients Undergoing Coronary Intervention with Drug-Eluting Stents or Bare-Metal Stents: A Nationwide Population Study.

BACKGROUND: The aim of this propensity score-matched cohort study was to investigate the prognostic impacts of drug-eluting stents (DES) and bare-metal stents (BMS) in patients undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a retrospective cohort study based on the National Health Insurance program. Patients who had undergone coronary stenting between Jan. 2007 and Dec. 2008 were recruited and monitored until the end of 2010. Subjects with either BMS or DES were matched 2:1 by propensity score, which adjusted for age, sex, stent number and Charlson comorbidity index (CCI). The Kaplan-Meier method and Cox regression models were used for prognostic analyses. RESULTS: Among a total of 966 patients with a mean age of 66 years, 644 subjects had BMS and 322 subjects had DES. The incidence of myocardial infarction (MI) and death were significantly lower in the DES group as compared with the BMS group for the three-year follow-up duration. With adjustments for age, sex, premium-based monthly salary, levels of hospital care, stent number, CCI, medications, and acute coronary syndrome presentation in the index hospitalization, use of DES rather than BMS was associated with reduced adverse coronary events (hazard ratio and 95% confidence interval: 0.55, 0.38-0.81 in the whole population, and 0.44, 0.26-0.73 in the subgroup patients with stable coronary artery disease). CONCLUSIONS: Implantation of DES was related to better outcomes than for BMS, in terms of reducing MI and mortality after PCI. The survival benefit for patients with DES was even greater in patients with stable coronary artery disease.

Over-activation in bilateral superior temporal gyrus correlated with subsequent forgetting effect of Chinese words.

We evaluated the subsequent memory and forgotten effects for Chinese using event-related fMRI. Sixteen normal subjects were recruited and performing incidental memory tasks where semantic decision was required during memory encoding. Consistent with previous studies, our results showed bilateral frontal regions as the main locus for the subsequent memory effect. However, contrast between miss and hit responses revealed larger activation in bilateral superior temporal gyrus. We proposed that larger activation in the superior temporal gyrus may reflect alteration of self-monitoring process which resulted in unsuccessful memory encoding for the miss items.

High neuromagnetic activation in the left prefrontal and frontal cortices correlates with better memory performance for abstract words.

The present study aimed to clarify the spatiotemporal characteristics of memory processing for abstract and concrete words. Neuromagnetic responses to memory encoding and recognition tasks of abstract and concrete nouns were obtained in 18 healthy adults using a whole-head neuromagnetometer. During memory encoding, abstract words elicited larger responses in the left temporal area 300-500 ms after the stimulus onset. The average peak latency of the right inferior frontal and left prefrontal responses to abstract words was about 70-85 ms longer than that to concrete words. Furthermore, greater activation in the left inferior frontal and anterior prefrontal regions was correlated with better recognition memory for abstract words. These findings are consistent with the proposition that both word types are processed with differential integration of semantic information. The present results suggest that the left prefrontal and frontal regions play an important role in both semantic and memory processing for abstract words.

Predictors for the immediate responders to cervical manipulation in patients with neck pain.

Cervical manipulation has been considered an effective treatment for managing neck pain. However, clinical observation showed that cervical manipulation was not effective for every patient. Development of clinical prediction rules for identifying patients with neck pain who are likely to respond to cervical manipulation may improve clinical decision-making and the treatment success rate. The purpose of the study was to identify predictors for the immediate responders to cervical manipulation treatment in patients with neck pain. One hundred patients with neck pain (34 males and 66 females, mean age = 46 +/- 11 years) participated in the study. Patient's demographic data, symptom aggravating or easing factors, pain, and disability level were obtained through an initial assessment. A series of physical examinations were also administered. After receiving a single session of cervical manipulation, the patient was re-evaluated immediately to determine if a successful response to treatment was obtained. The successful response was determined by improvements seen in one of the three outcome variables that included reduction of pain intensity, significant perceived improvement, and high satisfaction level. From these judgment criteria, patients were classified into either responders or nonresponders to the cervical manipulation. Univariate analyses were used to assess if the treatment responders and nonresponders were different in their clinical presentations. The clinical factors that showed significant differences between two groups were then entered into a stepwise multiple logistic regression analysis to identify significant predictors and the prediction rule for treatment responders. Six predictors including "initial scores on Neck Disability Index < 11.50", "having bilateral involvement pattern", "not performing sedentary work > 5 h/day", "feeling better while moving the neck", "without feeling worse while extending the neck", and "the diagnosis of spondylosis without radiculopathy" were identified to significantly predict the immediate responders. The presence of four or more of these predictors increased the probability of success with manipulation to 89%. We concluded that using favourable predictors to identify treatment responders before administering cervical manipulations could significantly increase the probabilities of a successful treatment. This study finding may enhance the efficacy of clinical decision-making in using cervical manipulation intervention.