Cortical Mechanisms of Multisensory Linear Self-motion Perception / 神经科学通报·英文版

Accurate self-motion perception, which is critical for organisms to survive, is a process involving multiple sensory cues. The two most powerful cues are visual (optic flow) and vestibular (inertial motion). Psychophysical studies have indicated that humans and nonhuman primates integrate the two cues to improve the estimation of self-motion direction, often in a statistically Bayesian-optimal way. In the last decade, single-unit recordings in awake, behaving animals have provided valuable neurophysiological data with a high spatial and temporal resolution, giving insight into possible neural mechanisms underlying multisensory self-motion perception. Here, we review these findings, along with new evidence from the most recent studies focusing on the temporal dynamics of signals in different modalities. We show that, in light of new data, conventional thoughts about the cortical mechanisms underlying visuo-vestibular integration for linear self-motion are challenged. We propose that different temporal component signals may mediate different functions, a possibility that requires future studies.

A Neural Circuit Controlling Virgin Female Aggression Induced by Mating-related Cues in Drosophila / 神经科学通报·英文版

Females increase aggression for mating opportunities and for acquiring reproductive resources. Although the close relationship between female aggression and mating status is widely appreciated, whether and how female aggression is regulated by mating-related cues remains poorly understood. Here we report an interesting observation that Drosophila virgin females initiate high-frequency attacks toward mated females. We identify 11-cis-vaccenyl acetate (cVA), a male-derived pheromone transferred to females during mating, which promotes virgin female aggression. We subsequently reveal a cVA-responsive neural circuit consisting of four orders of neurons, including Or67d, DA1, aSP-g, and pC1 neurons, that mediate cVA-induced virgin female aggression. We also determine that aSP-g neurons release acetylcholine (ACh) to excite pC1 neurons via the nicotinic ACh receptor nAChRα7. Together, beyond revealing cVA as a mating-related inducer of virgin female aggression, our results identify a neural circuit linking the chemosensory perception of mating-related cues to aggressive behavior in Drosophila females.

Differentiation of stem cells regulated by biophysical cues / 生物医学工程学杂志

Stem cells have been regarded with promising application potential in tissue engineering and regenerative medicine due to their self-renewal and multidirectional differentiation abilities. However, their fate is relied on their local microenvironment, or niche. Recent studied have demonstrated that biophysical factors, defined as physical microenvironment in which stem cells located play a vital role in regulating stem cell committed differentiation. In vitro, synthetic physical microenvironments can be used to precisely control a variety of biophysical properties. On this basis, the effect of biophysical properties such as matrix stiffness, matrix topography and mechanical force on the committed differentiation of stem cells was further investigated. This paper summarizes the approach of mechanical models of artificial physical microenvironment and reviews the effects of different biophysical characteristics on stem cell differentiation, in order to provide reference for future research and development in related fields.

A relação entre arte e vida em vigotski: uma análise conceitual / The relationship between art and life in vygotsky: a conceptual analysis / La relación entre arte y vida en vigotski: un análisis conceptual

Este trabalho teve como objetivo analisar a relação entre arte e vida segundo Vigotski. Para isso, foi realizada uma análise conceitual dos capítulos 1, 7, 9, 10 e 11 da Psicologia da Arte, do capítulo 13 da Psicologia Pedagógica e do texto O significado histórico da crise da Psicologia: Uma investigação metodológica. A pesquisa conceitual consiste na análise semântica dos principais conceitos de uma teoria com o intuito de elucidar seus sentidos ocultos ou confusos e desvendar possíveis contradições e ambiguidades no quadro teórico. Podemos observar que a arte é um fenômeno dialético tanto em sua criação como em seus efeitos. A influência da vida, isto é, da realidade sócio-histórica, na criação artística é indireta, pois ela é sempre mediada pelo psiquismo particular do artista. Já o efeito da arte sobre a vida possibilita que o ser humano se conscientize de sua realidade social e se engaje para mudá-la. A arte é, portanto, transformadora, pois reorganiza o psiquismo e possibilita uma mudança nas condições materiais dos seres humanos.(AU)

This study aims to analyze the relationship between art and life according to Vygotsky. Therefore, a conceptual analysis of chapters 1, 7, 9, 10, and 11 of Psychology of Art, chapter 13 of Educational Psychology and the text The Historical meaning of the Crisis of Psychology: A Methodological Investigation was carried out. Conceptual research consists of the semantic analysis of the main concepts of a theory to elucidate its hidden or confused meanings and to reveal possible contradictions and ambiguities in the theoretical framework. Results show that art is a dialectical phenomenon both in its creation and its effects. The influence of life, that is, of socio-historical reality, on artistic creation is indirect since it is always mediated by the artist's particular psyche. The effect of art on life, on the other hand, allows human beings to become aware of their social reality and engage to change it. Art is, therefore, transformative, as it reorganizes the psyche and enables a change in the material conditions of human beings.(AU)

Este proyecto tuve como objetivo analizar la relación entre el arte y la vida, según Vigotski. Para esto, fue realizado un análisis de los capítulos 1, 7, 9, 10 y 11 de Psicología del arte, del capítulo 13 de Psicología Pedagógica y del texto Él significado histórico de la crisis de la Psicología: una investigación metodológica. La pesquisa conceptual consiste en la analice semántica de los conceptos de una teoría, para aclarar sus significados ocultos o confusos y desvendar contradicciones y ambigüedades em el cuadro teórico. Pudimos observar que, el arte es un fenómeno dialéctico en su creación tanto como en sus efectos. La influencia de la vida, esto es, de la realidad socio-histórica, en la creación artística es indirecta, pues es mediada por el psiquismo particular de lo artista. Así, el efecto del arte sobre la vida habilita que lo ser humano adquiera conciencia de su realidad social y que se comprometa a cambiarla. El arte, consiguientemente, transformadora, pues reorganiza lo psiquismo y habilita un cambio en las condiciones materiales de los seres humanos.(AU)

Mother Behavior Q-Set (MBQS)Dimensionalidad del Q-set del comportamiento materno en muestras de México, Colombia y Uruguay / Mother Behavior Q-Set (MBQS): Dimensionality of the Mother Behavior Q-Set in samples from Mexico, Colombia and Uruguay

La sensibilidad se refiere a la capacidad del cuidador para percibir las señales del niño, interpretarlas correctamente y responder a ellas de manera contingente y apropiada. El Q Set del Comportamiento Materno (MBQS) fue creado a partir de descripciones teóricas y empíricas de la sensibilidad. Los Q-sorts se asocian con la metodología cuantitativa debido a que asignan puntajes; además, combinan la metodología cualitativa al hacer un estudio sistemático de la subjetividad. Son pocos los artículos que se ocupan de explorar el análisis, la validez interna, la confiabilidad o la replicabilidad externa de los Q-sorts. Usualmente los datos se reducen por medio de un análisis de componentes principales o análisis factorial. Sin embargo, en los Q-sorts se correlacionan los participantes para dilucidar las relaciones entre ellos en lugar de correlacionar las variables. El objetivo de la presente investigación fue encontrar evidencia respecto a la validez basada en la estructura interna del MBQS con el apoyo del software R y el paquete qmethod. Colaboraron 37 díadas mexicanas mamá-bebés, 35 colombianas y 24 uruguayas. En el 2002, Posada y colaboradores propusieron siete escalas. Las escalas en las que nuestro modelo factorial presentó un buen ajuste son las que tienen menos ítems, lo cual puede ser indicativo de que la falta de ajuste tiene que ver con la identificación del modelo debido a que se cuenta con pocas observaciones. Consideramos que tanto el uso del MBQS para evaluar la sensibilidad como del paquete qmethod para realizar el análisis resulta novedoso, relevante y pertinente

Sensitivity refers to the caregiver's ability to perceive infant's cues, interpret them correctly, and respond to them in a contingent and appropriate way. The Maternal Behavior Q Set (MBQS) was created from theoretical and empirical descriptions of sensitivity. Q-methodology is associated with the quantitative methodology because it assigns scores; in addition, it combines qualitative methodology by making a systematic study of subjectivity. Few papers are concerned with exploring the analysis, internal validity, reliability, or external replicability of Q studies. Usually analyses reduce data to a few summarizing factors, based on principal component analysis or centroid factor analysis. Q-factor analysis method was developed especially for q-sorted data; it is a by-person factor analysis which is used to identify groups of participants who make sense of a pool of items in comparable way. The aim of this study was to find evidence regarding the validity based on the internal structure of the MBQS using the R software and the qmethod package. Thirty-seven Mexican, 35 Colombian and 24 Uruguayan mother-baby dyads collaborated. In 2002, Posada et al. proposed seven scales. The scales in which our factorial model presented a good fit are those with the fewest items, which may be indicative that the lack of fit has to do with the identification of the model because there are few observations. We consider that both the use of the MBQS to assess sensitivity and the qmethod package to perform the analysis is novel, relevant and pertinent.

Real-Time Computed Tomography Volume Visualization with Ambient Occlusion of Hand-Drawn Transfer Function Using Local Vicinity Statistic / 대한의료정보학회지

OBJECTIVES: In this paper, we present an efficient method to visualize computed tomography (CT) datasets using ambient occlusion, which is a global illumination technique that adds depth cues to the output image. We can change the transfer function (TF) for volume rendering and generate output images in real time. METHODS: In preprocessing, the mean and standard deviation of each local vicinity are calculated. During rendering, the ambient light intensity is calculated. The calculation is accelerated on the assumption that the CT value of the local vicinity of each point follows the normal distribution. We approximate complex TF forms with a smaller number of connected line segments to achieve additional acceleration. Ambient occlusion is combined with the existing local illumination technique to produce images with depth in real time. RESULTS: We tested the proposed method on various CT datasets using hand-drawn TFs. The proposed method enabled real-time rendering that was approximately 40 times faster than the previous method. As a result of comparing the output image quality with that of the conventional method, the average signal-to-noise ratio was approximately 40 dB, and the image quality did not significantly deteriorate. CONCLUSIONS: When rendering CT images with various TFs, the proposed method generated depth-sensing images in real time.

Perception of Tamil Mono-Syllabic and Bi-Syllabic Words in Multi-Talker Speech Babble by Young Adults with Normal Hearing

BACKGROUND AND OBJECTIVES: This study compared the perception of mono-syllabic and bisyllabic words in Tamil by young normal hearing adults in the presence of multi-talker speech babble at two signal-to-noise ratios (SNRs). Further for this comparison, a speech perception in noise test was constructed using existing mono-syllabic and bi-syllabic word lists in Tamil. SUBJECTS AND METHODS: A total of 30 participants with normal hearing in the age range of 18 to 25 years participated in the study. Speech-in-noise test in Tamil (SPIN-T) constructed using mono-syllabic and bi-syllabic words in Tamil was used as stimuli. The stimuli were presented in the background of multi-talker speech babble at two SNRs (0 dB and +10 dB SNR). RESULTS: The effect of noise on SPIN-T varied with SNR. All the participants performed better at +10 dB SNR, the higher of the two SNRs considered. Additionally, at +10 dB SNR performance did not vary significantly for neither mono-syllabic or bi-syllabic words. However, a significant difference existed at 0 dB SNR. CONCLUSIONS: The current study indicated that higher SNR leads to better performance. In addition, bi-syllabic words were identified with minimal errors compared to mono-syllabic words. Spectral cues were the most affected in the presence of noise leading to more of place of articulation errors for both mono-syllabic and bi-syllabic words.

Designing and Evaluating Educational Intervention to Improve Preventive Behavior Against Cutaneous Leishmaniasis in Endemic Areas in Iran

OBJECTIVES: Health education programs are one of the most important strategies for controlling cutaneous leishmaniasis (CL) in endemic areas such as Neshabur city. This study aimed to develop and evaluate a comprehensive health education program to improve preventive behaviors for CL. METHODS: This was an interventional study conducted on 136 high school students in Neishabur city. Data collection instruments included a demographic questionnaire and a researcher-made questionnaire based on the “Health Belief Model” and “Beliefs, Attitudes, Subjective Norms and Enabling Factors Model” constructs. The control and intervention groups completed the questionnaires before and 2 months after the intervention. The intervention was conducted in 6, 1-hour educational sessions for the intervention group students and 2, 1-hour sessions for school administrators, teachers, and students’ parents. RESULTS: There was no significant difference between the 2 groups in the pre-intervention phase. However, in the post-intervention phase, there were significant differences between the 2 groups for mean scores of knowledge, perceived susceptibility, perceived severity, perceived benefits, cues to action, self-efficacy, attitude, subjective norms, behavioral intention, enabling factors, and behavior associated with CL. CONCLUSION: Health education program based on the “Health Belief Model” and the “Beliefs, Attitudes, Subjective Norms and Enabling Factors Model” model constructs may be a comprehensive and effective educational program to improve preventive behaviors against CL in students.

Processing mechanism of social cues in faces / 生理学报

The purpose of the present paper was to review the processing mechanisms of social cues in faces. We summarized researches relative to social cues in faces and discussed the processing mechanism of these cues from the aspects of facial expression, facial attractiveness, gaze and face direction, and lipreading. First, we discussed the general neural mechanism of face information processing and summarized the functions of face areas in the fusiform gyrus, posterior superior temporal sulcus and inferior occipital gyrus. Next, the neural mechanism of emotional face perception was discussed. The processing of emotional faces consists of encodings of perceptual and emotional components. The amygdala plays an important role in the emotional processing of facial expressions. Furthermore, the neural responses to facial expressions may be influenced by multiple factors, such as the type of emotion, the dynamic presentation of the face and the consciousness of facial expressions. With respect to facial attractiveness processing, studies has shown that the reward circuitry is activated by highly attractive faces. However, the influence of facial attractiveness on neural responses remains elusive. It is proposed that the neural responses to facial attractiveness might be modulated by factors such as the task, observer's sex, expectation and other social cues in faces. Eye gaze perception and face view perception are related to visual attention, and the relevant neural circuitry has been found to include attention-related areas, such as the intraparietal sulcus. Finally, research on lipreading reveals its important role in language perception. The auditory cortex and language-related cortex have been shown to be activated by lipreading. In summary, the present evidence may support facial information processing theory. However, the theory could be further improved based on present and future findings. Furthermore, we discussed the deficits in the processing of social cues in individuals with mental disorders and proposed future research directions in this field.

Efficacy of Virtual Reality in Upper Limb Rehabilitation in Patients with Spinal Cord Injury: A Pilot Randomized Controlled Trial

STUDY DESIGN: Pilot randomized controlled trial. PURPOSE: To compare the efficacy between virtual reality intervention (using Nintendo Wii) along with conventional occupational therapy and conventional occupational therapy alone in improving upper limb function in patients with spinal cord injury (SCI). OVERVIEW OF LITERATURE: The use of virtual reality has gained importance in the rehabilitation sector over the last few years. Nintendo Wii has the potential to encourage upper limb function while engaging in an interesting activity, which is important in long-term interventions, such as the treatment of SCI. METHODS: Overall, 22 patients with SCI participated in the study. They were randomly assigned to two groups. Group I received 30 minutes of virtual reality intervention (using Nintendo Wii) and 30 minutes of conventional therapy, whereas group II received conventional therapy only for 30 minutes. Both groups received therapy 3 days a week for 4 weeks. One hand of each patient was identified as the target hand based on the inclusion criteria. All patients were assessed at baseline, 2 weeks and 4 weeks (post-intervention), and 6 weeks (follow-up). The functional ability of the target hand was assessed using the Capabilities of Upper Extremity (CUE) questionnaire. Gross motor dexterity was assessed using the Box and Block Test (BBT). The level of independence in activities of daily living was assessed by the Spinal Cord Independence Measure-Self Report and quality of life by the World Health Organization Quality of Life-BREF. RESULTS: After 4 weeks of intervention, there was no significant difference in improved hand function between the groups. Mean scores were higher for group I than for group II, with a higher percent change (31.5% in CUE questionnaire and 51.7% in BBT) in group I. CONCLUSIONS: Virtual reality along with conventional therapy produces similar results in upper limb function as does conventional therapy alone.

Development of a Low-cost, Comprehensive Recording System for Circadian Rhythm Behavior

Circadian rhythm is defined as a 24-hour biological oscillation, which persists even without any external cues but also can be re-entrained by various environmental cues. One of the widely accepted circadian rhythm behavioral experiment is measuring the wheel-running activity (WRA) of rodents. However, the price for commercially available WRA recording system is not easily affordable for researchers due to high-cost implementation of sensors for wheel rotation. Here, we developed a cost-effective and comprehensive system for circadian rhythm recording by measuring the house-keeping activities (HKA). We have monitored animal's HKA as electrical signal by simply connecting animal housing cage with a standard analog/digital converter: input to the metal lid and ground to the metal grid floor. We show that acquired electrical signals are combined activities of eating, drinking and natural locomotor behaviors which are well-known indicators of circadian rhythm. Post-processing of measured electrical signals enabled us to draw actogram, which verifies HKA to be reliable circadian rhythm indicator. To provide easy access of HKA recording system for researchers, we have developed user-friendly MATLAB-based software, Circa Analysis. This software provides functions for easy extraction of scalable “touch activity” from raw data files by automating seven steps of post-processing and drawing actograms with highly intuitive user-interface and various options. With our cost-effective HKA circadian rhythm recording system, we have estimated the cost of our system to be less than $150 per channel. We anticipate our system will benefit many researchers who would like to study circadian rhythm.

A Critical Time-Window for the Selective Induction of Hippocampal Memory Consolidation by a Brief Episode of Slow-Wave Sleep / 神经科学通报·英文版

Although extensively studied, the exact role of sleep in learning and memory is still not very clear. Sleep deprivation has been most frequently used to explore the effects of sleep on learning and memory, but the results from such studies are inevitably complicated by concurrent stress and distress. Furthermore, it is not clear whether there is a strict time-window between sleep and memory consolidation. In the present study we were able to induce time-locked slow-wave sleep (SWS) in mice by optogenetically stimulating GABAergic neurons in the parafacial zone (PZ), providing a direct approach to analyze the influences of SWS on learning and memory with precise time-windows. We found that SWS induced by light for 30 min immediately or 15 min after the training phase of the object-in-place task significantly prolonged the memory from 30 min to 6 h. However, induction of SWS 30 min after the training phase did not improve memory, suggesting a critical time-window between the induction of a brief episode of SWS and learning for memory consolidation. Application of a gentle touch to the mice during light stimulation to prevent SWS induction also failed to improve memory, indicating the specific role of SWS, but not the activation of PZ GABAergic neurons itself, in memory consolidation. Similar influences of light-induced SWS on memory consolidation also occurred for Y-maze spatial memory and contextual fear memory, but not for cued fear memory. SWS induction immediately before the test phase had no effect on memory performance, indicating that SWS does not affect memory retrieval. Thus, by induction of a brief-episode SWS we have revealed a critical time window for the consolidation of hippocampus-dependent memory.

Frequency-Limiting Effects on Speech and Environmental Sound Identification for Cochlear Implant and Normal Hearing Listeners

BACKGROUND AND OBJECTIVES: It is important to understand the frequency region of cues used, and not used, by cochlear implant (CI) recipients. Speech and environmental sound recognition by individuals with CI and normal-hearing (NH) was measured. Gradients were also computed to evaluate the pattern of change in identification performance with respect to the low-pass filtering or high-pass filtering cutoff frequencies. SUBJECTS AND METHODS: Frequency-limiting effects were implemented in the acoustic waveforms by passing the signals through low-pass filters (LPFs) or high-pass filters (HPFs) with seven different cutoff frequencies. Identification of Korean vowels and consonants produced by a male and female speaker and environmental sounds was measured. Crossover frequencies were determined for each identification test, where the LPF and HPF conditions show the identical identification scores. RESULTS: CI and NH subjects showed changes in identification performance in a similar manner as a function of cutoff frequency for the LPF and HPF conditions, suggesting that the degraded spectral information in the acoustic signals may similarly constraint the identification performance for both subject groups. However, CI subjects were generally less efficient than NH subjects in using the limited spectral information for speech and environmental sound identification due to the inefficient coding of acoustic cues through the CI sound processors. CONCLUSIONS: This finding will provide vital information in Korean for understanding how different the frequency information is in receiving speech and environmental sounds by CI processor from normal hearing.

Dynamics of Speech Perception in the Auditory-Visual Mode: An Empirical Evidence for the Management of Auditory Neuropathy Spectrum Disorders

BACKGROUND AND OBJECTIVES: The present study probed into the relative and combined contribution of auditory and visual modalities in the speech perception of individuals with auditory neuropathy spectrum disorders (ANSD). Specifically, the identification scores of consonant-vowel (CV) syllables, visual enhancement (VE), and auditory enhancement in different signal to noise ratios (SNRs) were compared with that of the control group. SUBJECTS AND METHODS: The study used a repeated measure standard group comparison research design. Two groups of individuals in the age range of 16 to 35 years participated in the study. The clinical group included 35 participants diagnosed as ANSD, while the control group had 35 age and gender matched individuals with typical auditory abilities. The participants were assessed for CV syllable identification in auditory only (A), visual only (V), and auditory-visual (AV) modalities. The syllables were presented in quiet and at 0 dB SNR. RESULTS: The speech identification score was maximum in AV condition followed by A-condition and least in V condition. This was true in both the groups. The individuals with ANSD were able to make better use of visual cues than the control group, as evident in the VE score. CONCLUSIONS: The dynamics of speech perception in the AV mode is different between ANSD and control. There is definite benefit of auditory as well as visual cues to individuals with ANSD, suggesting the need to facilitate both the modalities as part of the audiological rehabilitation. Future studies can focus on independently facilitating the two modalities and testing the benefits in the AV mode of speech perception in individuals with ANSD.

The Assessment of Eyewitness Memory Using Electroencephalogram: Application of Machine Learning Algorithm / 대한법의학회지

This study was conducted to investigate whether memory accuracy can be assessed by analyzing electrophysiological responses (i.e., electroencephalography [EEG]) for retrieval cues related to the witnessed scene. Specifically, we examined the different patterns of EEG signals recorded during witnessed (target) and unwitnessed (lure) stimuli using event-related potential (ERP) analysis. Moreover, using multivariate pattern analysis, we also assessed how accurately single-trial EEG signals can classify target and lure stimuli. Participants watched a staged-crime video (theft crime), and the EEG signals evoked by the objects shown in the video were analyzed (n=56). Compared to the target stimulus, the lure stimulus elicited larger negative ERPs in frontal brain regions 300 to 500 milliseconds after the retrieval cue was presented. Furthermore, the EEG signals observed 450 to 500 milliseconds after the retrieval cue was presented showed the best classification performance related to eyewitness memory, with the mean classification accuracy being 56%. These results suggest that the knowledge and techniques of cognitive neuroscience can be used to estimate eyewitness memory accuracy.

Usefulness of Korean Version of Behavioral Cue Checklist for Predicting of Patient Violence in Emergency Departments

PURPOSE: This study aimed to evaluate the usefulness of a behavioral cue checklist (BCC) containing 17 items developed by Wilkes et al. (2010) for identifying potentially violent patients in emergency departments. METHODS: This was a prospective observational study to evaluate the usefulness of the Korean version of a BCC (K-BCC) as an assessment tool for predicting patient violence in emergency departments, and was conducted over 4 weeks in a regional emergency medical center located in B City. A total of 1,324 patients were finally analyzed. RESULTS: Logistic regression analysis was performed to investigate whether each item of the K-BCC predicts violence, and a parsimonious set of 8 statistically significant items was selected for the tool. Receiver operating characteristic analysis of the BCC showed that the area under the curve was .97 (95% confidence interval: .94~1.0). The sensitivity, specificity, positive predictive value, and negative predictive value at the cut-off score of 2 were 75.6%, 98.9%, 68.2%, and 99.2%, respectively. CONCLUSION: The K-BCC was found to be useful in predicting patient violence toward emergency department staff. This tool is simple, and fast to use and can play a significantly role identifying potentially violent patients. Owing to this advance identification, this tool can be helpful in preventing the potential for violence from manifesting as violent behaviors.

Distinct Ultradian Rhythms in Plasma Clusterin Concentrations in Lean and Obese Korean Subjects

BACKGROUND: Blood levels of many hormones show rhythmic fluctuations with variable duration of cycles. Clusterin/apolipoprotein J is a glycoprotein which is highly expressed in the plasma and has modulatory roles in immune and inflammatory reactions, neurobiology, lipid metabolism, and leptin signaling. In this study, we examined the diurnal fluctuations of plasma clusterin concentrations in lean and obese young men. METHODS: For the study, 14 subjects (five lean and five obese men; two lean and two obese women) were admitted to the research ward and blood samples were drawn every 30 minutes during light-on period (6:00 AM to 10:00 PM) and every hour during light-off period. RESULTS: Notably, plasma clusterin concentrations displayed a unique ultradian rhythm with five cycles a day in both men and women. During the light-on period, circulating clusterin levels showed fluctuating curves with 4 hours regular intervals with sharp peaks and troughs. In contrast, single oscillation curve during light-off exhibited a smoothened/lower peak and longer (8-hour) duration. In obese men, these cycles were phase-advanced by approximately 1 hour, and had reduced amplitude of fluctuating curves and blunted diurnal pattern. Cyclic fluctuations of plasma clusterin were preserved under fasting and unexpected meal condition, suggesting that rhythmic oscillations in plasma clusterin levels are not generated by meal-related cues. CONCLUSION: These findings firstly demonstrate a novel pattern of plasma clusterin fluctuations with extremely regular cycles.

Fabrication of Microchannels and Evaluation of Guided Vascularization in Biomimetic Hydrogels

BACKGROUND: The fabrication of microchannels in hydrogel can facilitate the perfusion of nutrients and oxygen, which leads to guidance cues for vasculogenesis. Microchannel patterning in biomimetic hydrogels is a challenging issue for tissue regeneration because of the inherent low formability of hydrogels in a complex configuration. We fabricated microchannels using wire network molding and immobilized the angiogenic factors in the hydrogel and evaluated the vasculogenesis in vitro and in vivo. METHODS: Microchannels were fabricated in a hyaluronic acid-based biomimetic hydrogel by using “wire network molding” technology. Substance P was immobilized in acrylated hyaluronic acid for angiogenic cues using Michael type addition reaction. In vitro and in vivo angiogenic activities of hydrogel with microchannels were evaluated. RESULTS: In vitro cell culture experiment shows that cell viability in two experimental biomimetic hydrogels (with microchannels and microchannels + SP) was higher than that of a biomimetic hydrogel without microchannels (bulk group). Evaluation on differentiation of human mesenchymal stem cells (hMSCs) in biomimetic hydrogels with fabricated microchannels shows that the differentiation of hMSC into endothelial cells was significantly increased compared with that of the bulk group. In vivo angiogenesis analysis shows that thin blood vessels of approximately 25–30 µm in diameter were observed in the microchannel group and microchannel + SP group, whereas not seen in the bulk group. CONCLUSION: The strategy of fabricating microchannels in a biomimetic hydrogel and simultaneously providing a chemical cue for angiogenesis is a promising formula for large-scale tissue regeneration.

Combination of Mesenchymal Stem Cells, Cartilage Pellet and Bioscaffold Supported Cartilage Regeneration of a Full Thickness Articular Surface Defect in Rabbits

BACKGROUND: Mesenchymal stem cells (MSCs) and/or biological scaffolds have been used to regenerate articular cartilage with variable success. In the present study we evaluated cartilage regeneration using a combination of bone marrow (BM)-MSCs, Hyalofast™ and/or native cartilage tissue following full thickness surgical cartilage defect in rabbits. METHODS: Full-thickness surgical ablation of the medial-tibial cartilage was performed in New Zealand white (NZW) rabbits. Control rabbits (Group-I) received no treatment; Animals in other groups were treated as follows. Group-II: BMMSCs (1 × 10⁶ cells) + Hyalofast™; Group-III: BMMSCs (1 × 10⁶ cells) + cartilage pellet (CP); and Group-IV: BMMSCs (1 × 10⁶ cells) + Hyalofast™+ CP. Animals were sacrificed at 12 weeks and cartilage regeneration analyzed using histopathology, International Cartilage Repair Society (ICRS-II) score, magnetic resonance observation of cartilage repair tissue (MOCART) score and biomechanical studies. RESULTS: Gross images showed good tissue repair (Groups IV>III>Group II) and histology demonstrated intact superficial layer, normal chondrocyte arrangement, tidemark and cartilage matrix staining (Groups III and IV) compared to the untreated control (Group I) respectively. ICRS-II score was 52.5, 65.0, 66 and 75% (Groups I–IV) and the MOCART score was 50.0, 73.75 and 76.25 (Groups II–IV) respectively. Biomechanical properties of the regenerated cartilage tissue in Group IV closed resembled that of a normal cartilage. CONCLUSION: Hyalofast™ together with BM-MSCs and CP led to efficient cartilage regeneration following full thickness surgical ablation of tibial articular cartilage in vivo in rabbits. Presence of hyaluronic acid in the scaffold and native microenvironment cues probably facilitated differentiation and integration of BM-MSCs.

Development and Evaluation of Hyaluronic Acid-Based Hybrid Bio-Ink for Tissue Regeneration

BACKGROUND: Bioprinting has recently appeared as a powerful tool for building complex tissue and organ structures. However, the application of bioprinting to regenerative medicine has limitations, due to the restricted choices of bio-ink for cytocompatible cell encapsulation and the integrity of the fabricated structures. METHODS: In this study, we developed hybrid bio-inks based on acrylated hyaluronic acid (HA) for immobilizing bioactive peptides and tyramine-conjugated hyaluronic acids for fast gelation. RESULTS: Conventional acrylated HA-based hydrogels have a gelation time of more than 30 min, whereas hybrid bioink has been rapidly gelated within 200 s. Fibroblast cells cultured in this hybrid bio-ink up to 7 days showed < 90% viability. As a guidance cue for stem cell differentiation, we immobilized four different bio-active peptides: BMP-7-derived peptides (BMP-7D) and osteopontin for osteogenesis, and substance-P (SP) and Ac-SDKP (SDKP) for angiogenesis. Mesenchymal stem cells cultured in these hybrid bio-inks showed the highest angiogenic and osteogenic activity cultured in bio-ink immobilized with a SP or BMP-7D peptide. This bio-ink was loaded in a three-dimensional (3D) bioprinting device showing reproducible printing features. CONCLUSION: We have developed bio-inks that combine biochemical and mechanical cues. Biochemical cues were able to regulate differentiation of cells, and mechanical cues enabled printing structuring. This multi-functional bio-ink can be used for complex tissue engineering and regenerative medicine.