Recurrent Neural Network Methods for Extracting Dynamic Balance Variables during Gait from a Single Inertial Measurement Unit.

Monitoring dynamic balance during gait is critical for fall prevention in the elderly. The current study aimed to develop recurrent neural network models for extracting balance variables from a single inertial measurement unit (IMU) placed on the sacrum during walking. Thirteen healthy young and thirteen healthy older adults wore the IMU during walking and the ground truth of the inclination angles (IA) of the center of pressure to the center of mass vector and their rates of changes (RCIA) were measured simultaneously. The IA, RCIA, and IMU data were used to train four models (uni-LSTM, bi-LSTM, uni-GRU, and bi-GRU), with 10% of the data reserved to evaluate the model errors in terms of the root-mean-squared errors (RMSEs) and percentage relative RMSEs (rRMSEs). Independent t-tests were used for between-group comparisons. The sensitivity, specificity, and Pearson's r for the effect sizes between the model-predicted data and experimental ground truth were also obtained. The bi-GRU with the weighted MSE model was found to have the highest prediction accuracy, computational efficiency, and the best ability in identifying statistical between-group differences when compared with the ground truth, which would be the best choice for the prolonged real-life monitoring of gait balance for fall risk management in the elderly.

[Retrospective on ESP Courses in the Global English Era].

With the rise of the medical tourism industry in Taiwan and changes in the country's population structure, nurses are facing greater challenges than ever before. Both professional knowledge and English proficiency are indispensable. Various types of English for Specific Purposes (ESP) courses have emerged to assist healthcare professionals to build their English abilities and cope with the changing demands of their profession. However, related research indicates that the deficient state of English communication skills among nurses in Taiwan may hinder the country's ability to effectively promote medical internationalization and handle ongoing changes in its population structure. To effectively face this predicament, educators must re-examine the current design of ESP courses. Therefore, this article was developed to explore ESP courses from the three perspectives of language descriptions, needs analysis, and learning theories. Furthermore, the concepts and research related to these three perspectives, including the nurse-patient relationship, community of practice, situated learning, and English as a medium of instruction, were reviewed. Some insights into how these concepts may be applied to ESP courses are also proposed with the goals of better incorporating the needs of learners into course designs and placing learners at the center of language learning.

Novelty and Novel Objects Increase c-Fos Immunoreactivity in Mossy Cells in the Mouse Dentate Gyrus.

The dentate gyrus (DG) and its primary cell type, the granule cell (GC), are thought to be critical to many cognitive functions. A major neuronal subtype of the DG is the hilar mossy cell (MC). MCs have been considered to play an important role in cognition, but in vivo studies to understand the activity of MCs during cognitive tasks are challenging because the experiments usually involve trauma to the overlying hippocampus or DG, which kills hilar neurons. In addition, restraint typically occurs, and MC activity is reduced by brief restraint stress. Social isolation often occurs and is potentially confounding. Therefore, we used c-fos protein expression to understand when MCs are active in vivo in socially housed adult C57BL/6 mice in their home cage. We focused on c-fos protein expression after animals explored novel objects, based on previous work which showed that MCs express c-fos protein readily in response to a novel housing location. Also, MCs are required for the training component of the novel object location task and novelty-encoding during a food-related task. GluR2/3 was used as a marker of MCs. The results showed that MC c-fos protein is greatly increased after exposure to novel objects, especially in ventral DG. We also found that novel objects produced higher c-fos levels than familiar objects. Interestingly, a small subset of neurons that did not express GluR2/3 also increased c-fos protein after novel object exposure. In contrast, GCs appeared relatively insensitive. The results support a growing appreciation of the role of the DG in novelty detection and novel object recognition, where hilar neurons and especially MCs are very sensitive.

Deletion of CPEB3 enhances hippocampus-dependent memory via increasing expressions of PSD95 and NMDA receptors.

Long-term memory requires activity-dependent synthesis of plasticity-related proteins (PRPs) to strengthen synaptic efficacy and consequently consolidate memory. Cytoplasmic polyadenylation element binding protein (CPEB)3 is a sequence-specific RNA-binding protein that regulates translation of several PRP RNAs in neurons. To understand whether CPEB3 plays a part in learning and memory, we generated CPEB3 knock-out (KO) mice and found that the null mice exhibited enhanced hippocampus-dependent, short-term fear memory in the contextual fear conditioning test and long-term spatial memory in the Morris water maze. The basal synaptic transmission of Schaffer collateral-CA1 neurons was normal but long-term depression evoked by paired-pulse low-frequency stimulation was modestly facilitated in the juvenile KO mice. Molecular and cellular characterizations revealed several molecules in regulating plasticity of glutamatergic synapses are translationally elevated in the CPEB3 KO neurons, including the scaffolding protein PSD95 and the NMDA receptors along with the known CPEB3 target, GluA1. Together, CPEB3 functions as a negative regulator to confine the strength of glutamatergic synapses by downregulating the expression of multiple PRPs and plays a role underlying certain forms of hippocampus-dependent memories.

NMDAR signaling facilitates the IPO5-mediated nuclear import of CPEB3.

Cytoplasmic polyadenylation element-binding protein (CPEB)3 is a nucleocytoplasm-shuttling RNA-binding protein and predominantly resides in the cytoplasm where it represses target RNA translation. When translocated into the nucleus, CPEB3 binds to Stat5b and downregulates Stat5b-dependent transcription. In neurons, the activation of N-methyl-d-aspartate receptors (NMDARs) accumulates CPEB3 in the nucleus and redistributes CPEB3 in the nucleocytoplasmic compartments to control gene expression. Nonetheless, it is unclear which karyopherin drives the nuclear import of CPEB3 and which transport direction is most affected by NMDA stimulation to increase the nuclear pool of CPEB3. Here, we have identified that the karyopherins, IPO5 and CRM1, facilitate CPEB3 translocation by binding to RRM1 and a leucine-containing motif of CPEB3, respectively. NMDAR signaling increases RanBP1 expression and reduces the level of cytoplasmic GTP-bound Ran. These changes enhance CPEB3-IPO5 interaction, which consequently accelerates the nuclear import of CPEB3. This study uncovers a novel NMDA-regulated import pathway to facilitate the nuclear translocation of CPEB3.

New Insights and Methods for Recording and Imaging Spontaneous Spreading Depolarizations and Seizure-Like Events in Mouse Hippocampal Slices.

Spreading depolarization (SD) is a sudden, large, and synchronous depolarization of principal cells which also involves interneurons and astrocytes. It is followed by depression of neuronal activity, and it slowly propagates across brain regions like cortex or hippocampus. SD is considered to be mechanistically relevant to migraine, epilepsy, and traumatic brain injury (TBI), but there are many questions about its basic neurophysiology and spread. Research into SD in hippocampus using slices is often used to gain insight and SD is usually triggered by a focal stimulus with or without an altered extracellular buffer. Here, we optimize an in vitro experimental model allowing us to record SD without focal stimulation, which we call spontaneous. This method uses only an altered extracellular buffer containing 0 mM Mg2+ and 5 mM K+ and makes it possible for simultaneous patch and extracellular recording in a submerged chamber plus intrinsic optical imaging in slices of either sex. We also add methods for quantification and show the quantified optical signal is much more complex than imaging alone would suggest. In brief, acute hippocampal slices were prepared with a chamber holding a submerged slice but with flow of artificial cerebrospinal fluid (aCSF) above and below, which we call interface-like. As soon as slices were placed in the chamber, aCSF with 0 Mg2+/5 K+ was used. Most mouse slices developed SD and did so in the first hour of 0 Mg2+/5 K+ aCSF exposure. In addition, prolonged bursts we call seizure-like events (SLEs) occurred, and the interactions between SD and SLEs suggest potentially important relationships. Differences between rats and mice in different chambers are described. Regarding optical imaging, SD originated in CA3 and the pattern of spread to CA1 and the dentate gyrus was similar in some ways to prior studies but also showed interesting differences. In summary, the methods are easy to use, provide new opportunities to study SD, new insights, and are inexpensive. They support previous suggestions that SD is diverse, and also suggest that participation by the dentate gyrus merits greater attention.

Mental Adjustment as a Predictor of Comprehensive Quality of Life Outcome among Patients with Terminal Cancer.

Using path modeling, this study aimed to explore whether mental adjustment was directly or indirectly related to comprehensive quality of life outcome (CoQoLO) among patients with terminal cancer. We conducted a cross-sectional designed study among patients with terminal cancer who underwent convenience sampling at our northern Taiwan clinic from August 2019 to August 2020. Patient characteristics data were collected via structured questionnaires, namely, the Mini-Mental Adjustment to Cancer Scale and the Comprehensive Quality of Life Outcome Inventory. Descriptive statistics and regression analyses were used to examine the relationship between mental adjustment and CoQoLO. Path analysis described the dependencies among variables. For the 117 enrolled patients analyzed, MAC (ß = 1.2, 95% confidence interval (CI) = 0.8-1.6, p < 0.001) and living with others (ß = 19.9, 95% CI = 4.1-35.7, p = 0.015) were significant predictors and correlated positively with a CoQoLO score. Path modeling showed that the patients' mental adjustment, economic status, perceived disease severity, palliative prognostic index, and symptom severity directly affected their CoQoLO. Our results indicate that the higher the mental adjustment, the better the CoQoLO among patients with terminal cancer. Thus, nurses need to assess mental adjustment levels when patients are hospitalized and accordingly develop interventions to improve the terminally ill patients' mental adjustment to the final stages of cancer, thereby helping them to achieve good CoQoLO.

How do nurses acquire English medical discourse ability in nursing practice? Exploring nurses' medical discourse learning journeys and related identity construction.

BACKGROUND: In Taiwan's hospitals, English medical discourse underpins nursing and medical practice. Much patient care work is done through language work, by both text and talk. This means that when nurses start their nursing careers in the hospital context, where English medical discourse is shared to produce knowledge and engage in practice, knowledge of medical discourse and the ability to use it are prerequisites. In the process of learning and using such specialist language, the formation of professional identities is assumed. OBJECTIVES: This study aimed to explore nurses' learning journeys relating to medical discourse and the development of their professional identities. METHODS: This research adopted a qualitative approach, using data from 10 nurses working in different hospitals in Taiwan. RESULTS: The findings revealed that English medical discourse was employed in Taiwan's hospitals not only for fulfilling professional purposes but also for socialising nurses into the healthcare community. Nurses acquired it through interactions, small talk, relationships, discussions, and nursing tasks. Their professional identities were formed through engaging in meaningful nursing practice based on English medical discourse. However, in the learning process, they encountered difficulties in the areas of listening, speaking, and reading, which raised concerns about patient safety. CONCLUSION: Sufficient support is needed to ease nurses' difficulties in learning. We propose having primary and secondary preceptors, establishing a mentorship policy, and creating a learning environment that is supportive of nurses' learning experiences.

Dermis-fat graft as treatment of early implant exposure in a postpenetrating keratoplasty patient with nontraumatic eyeball rupture.

Orbital implant exposure may be the most common complication after evisceration surgery with orbital implantation. Management of implant exposure is a vital issue for oculoplastic surgeons. We present the case of a patient with nontraumatic eyeball rupture receiving dermis-fat graft after early implant exposure. The present case with multiple penetrating keratoplasty history underwent emergent evisceration and silicon sphere implantation due to nontraumatic eyeball rupture with severe uvea prolapse. The surrounding corneal tissue of the rupture aperture was almost unidentified before the operation. Deep superior sulcus syndrome and orbital implant exposure developed 2 months after the operation; hence, orbital reconstruction and dermis-fat graft transplantation were performed. Orbital reconstruction and orbital implant exposure management are discussed in the content.

Seasonal abundance of vectors at outdoor environments in endemic and nonendemic districts of dengue in Kaohsiung, South Taiwan.

This study was designed to determine the seasonal variation in abundance of dengue vectors at open spaces, empty houses, parks, and markets in endemic and nonendemic districts of dengue. Ovitraps were placed in these sites from March 2003 to January 2004 in Kaohsiung Area (Kaohsiung City and Kaohsiung County), South Taiwan. The index peaked in May, June, and September in the endemic districts and in May and October in nonendemic districts. The egg production of the vectors increased from April on and peaked in September. Aedes albopictus had a significant higher proportion than A. aegypti throughout the study period and in both districts. Although ovitrap indices at open spaces, empty houses, and parks were significantly higher than those in nearby households, no significant difference was found between markets and households. Moreover, the outdoor ovitrap index was significantly higher than the indoor one. No significant difference was found between the endemic and nonendemic districts in egg production, vector maturation, vector abundance at the outdoor environments, or nearby households. These findings indicate the importance of the environmental conditions surrounding the human dwelling sites in the transmission of dengue. Measures applied to remove dengue vectors should include these sites but also outdoor environments as well.

Genetic Elimination of Connective Tissue Growth Factor in the Forebrain Affects Subplate Neurons in the Cortex and Oligodendrocytes in the Underlying White Matter.

Connective tissue growth factor (CTGF) is a secreted extracellular matrix-associated protein, which play a role in regulating various cellular functions. Although the expression of CTGF has been reported in the cortical subplate, its function is still not clear. Thus, to explore the significance of CTGF in the brain, we created a forebrain-specific Ctgf knockout (FbCtgf KO) mouse model. By crossing Ctgf fl/fl mice with Emx1-Cre transgenic mice, in which the expression of Cre is prenatally initiated, the full length Ctgf is removed in the forebrain structures. In young adult (2-3 months old) FbCtgf KO mice, subplate markers such as Nurr1 and Cplx3 are still expressed in the cortical layer VIb; however, the density of the subplate neurons is increased. Interestingly, in these mutants, we found a reduced structural complexity in the subplate neurons. The distribution patterns of neurons and glial cells, examined by immunohistochemistry, are comparable between genotypes in the somatosensory cortex. However, increased densities of mature oligodendrocytes, but not immature ones, were noticed in the external capsule underneath the cortical layer VIb in young adult FbCtgf KO mice. The features of myelinated axons in the external capsule were then examined using electron microscopy. Unexpectedly, the thickness of the myelin sheath was reduced in middle-aged (>12 months old), but not young adult FbCtgf KO mice. Our results suggest a secretory function of the subplate neurons, through the release of CTGF, which regulates the density and dendritic branching of subplate neurons as well as the maturation and function of nearby oligodendrocytes in the white matter.

An Excitatory and Epileptogenic Effect of Dentate Gyrus Mossy Cells in a Mouse Model of Epilepsy.

The sparse activity of hippocampal dentate gyrus (DG) granule cells (GCs) is thought to be critical for cognition and behavior, whereas excessive DG activity may contribute to disorders such as temporal lobe epilepsy (TLE). Glutamatergic mossy cells (MCs) of the DG are potentially critical to normal and pathological functions of the DG because they can regulate GC activity through innervation of GCs or indirectly through GABAergic neurons. Here, we test the hypothesis that MC excitation of GCs is normally weak, but under pathological conditions, MC excitation of GCs is dramatically strengthened. We show that selectively inhibiting MCs during severe seizures reduced manifestations of those seizures, hippocampal injury, and chronic epilepsy. In contrast, selectively activating MCs was pro-convulsant. Mechanistic in vitro studies using optogenetics further demonstrated the unanticipated ability of MC axons to excite GCs under pathological conditions. These results demonstrate an excitatory and epileptogenic effect of MCs in the DG.

Impact of Cold Ischemic Time and Freeze-Thaw Cycles on RNA, DNA and Protein Quality in Colorectal Cancer Tissues Biobanking.

Tissue-derived RNA, DNA and protein samples become more and more crucial for molecular detection in clinical research, personalized and targeted cancer therapy. This study evaluated how to biobanking colorectal tissues through examining the influences of cold ischemic time and freeze-thaw cycles on RNA, DNA and protein integrity. Here, 144 pairs of tumor and normal colorectal tissues were used to investigate the impact of cold ischemic times (0-48h) on RNA, DNA and protein integrity at on ice or room temperature conditions. Additionally, 45 pairs of tissues experienced 0-9 freeze-thaw cycles, and then the RNA, DNA and protein quality were analyzed. On ice, RNA, DNA and protein from colorectal tumor and normal tissues were all stable up to 48h after surgery. At room temperature, RNA in colorectal tumor and normal tissues began to degrade at 8h and 24h, respectively. Meanwhile, the tumor tissues DNA degradation occurred at 24h after surgery at room temperature. Similarly, the protein expression level of tumor and normal tissues began to change at 24h after the surgery at room temperature. Interestingly, tissue RNA and DNA remained stable even after 9 freeze-thaw cycles, whereas the proteins levels were remarkably changed after 7 freeze-thaw cycles. This study provided a useful evidence on how to store human colorectal tissues for biobanking. Preserving the surgical colorectal tissue on ice was an effective way to prevent RNA, DNA and protein degradation. Importantly, more than 7 repeated freeze-thaw cycles were not recommended for colorectal tissues.

Corticotropin-releasing factor in ventromedial prefrontal cortex mediates avoidance of a traumatic stress-paired context.

Post-traumatic stress disorder (PTSD) affects 7.7 million Americans. One diagnostic criterion for PTSD is avoidance of stimuli that are related to the traumatic stress. Using a predator odor stress conditioned place aversion (CPA) model, rats can be divided into groups based on stress reactivity, as measured by avoidance of the odor-paired context. Avoider rats, which show high stress reactivity, exhibit persistent avoidance of stress-paired context and escalated alcohol drinking. Here, we examined the potential role of corticotropin-releasing factor (CRF), a neuropeptide that promotes anxiety-like behavior in mediating avoidance and escalated alcohol drinking after stress. CRF is expressed in the medial prefrontal cortex (mPFC). The dorsal and ventral sub-regions of the mPFC (dmPFC and vmPFC) have opposing roles in stress reactivity and alcohol drinking. We hypothesized that vmPFC CRF-CRFR1 signaling contributes functionally to stress-induced avoidance and escalated alcohol self-administration. In Experiment 1, adult male Wistar rats were exposed to predator odor stress in a CPA paradigm, indexed for avoidance of odor-paired context, and brains processed for CRF-immunoreactive cell density in vmPFC and dmPFC. Post-stress, Avoiders exhibited higher CRF cell density in vmPFC, but not the dmPFC. In Experiment 2, rats were tested for avoidance of a context repeatedly paired with intra-vmPFC CRF infusions. In Experiment 3, rats were stressed and indexed, then tested for the effects of intra-vmPFC CRFR1 antagonism on avoidance and alcohol self-administration. Intra-vmPFC CRF infusion produced avoidance of a paired context, and intra-vmPFC CRFR1 antagonism reversed avoidance of a stress-paired context, but did not alter post-stress alcohol self-administration. These findings suggest that vmPFC CRF-CRFR1 signaling mediates avoidance of stimuli paired with traumatic stress.

Hilar granule cells of the mouse dentate gyrus: effects of age, septotemporal location, strain, and selective deletion of the proapoptotic gene BAX.

The dentate gyrus (DG) principal cells are glutamatergic granule cells (GCs), and they are located in a compact cell layer. However, GCs are also present in the adjacent hilar region, but have been described in only a few studies. Therefore, we used the transcription factor prospero homeobox 1 (Prox1) to quantify GCs at postnatal day (PND) 16, 30, and 60 in a common mouse strain, C57BL/6J mice. At PND16, there was a large population of Prox1-immunoreactive (ir) hilar cells, with more in the septal than temporal hippocampus. At PND30 and 60, the size of the hilar Prox1-ir cell population was reduced. Similar numbers of hilar Prox1-expressing cells were observed in PND30 and 60 Swiss Webster mice. Prox1 is usually considered to be a marker of postmitotic GCs. However, many Prox1-ir hilar cells, especially at PND16, were not double-labeled with NeuN, a marker typically found in mature neurons. Most hilar Prox1-positive cells at PND16 co-expressed doublecortin (DCX) and calretinin, markers of immature GCs. Double-labeling with a marker of actively dividing cells, Ki67, was not detected. These results suggest that, surprisingly, a large population of cells in the hilus at PND16 are immature GCs (Type 2b and Type 3 cells). We also asked whether hilar Prox1-ir cell numbers are modifiable. To examine this issue, we conditionally deleted the proapoptotic gene BAX in Nestin-expressing cells at a time when there are numerous immature GCs in the hilus, PND2-8. When these mice were examined at PND60, the numbers of Prox1-ir hilar cells were significantly increased compared to control mice. However, deletion of BAX did not appear to change the proportion that co-expressed NeuN, suggesting that the size of the hilar Prox1-expressing population is modifiable. However, deleting BAX, a major developmental disruption, does not appear to change the proportion that ultimately becomes neurons.

Experiences in the workplace community and the influence of community experiences on ENP courses for nursing professionals.

BACKGROUND: A nursing community can be described as a discourse community or a Community of Practice (CoP). No matter what type, a nursing community exerts influences on its group members' worldviews, perspectives and beliefs. OBJECTIVES: The purpose of this research is to explore what nurses' experiences of membership within the nursing community are and how such experiences influence nurses' views of English for nursing purposes (ENP) courses. DESIGN: A qualitative case study was conducted in a medical centre in Taiwan in which many foreign patients seek medical treatment and in which English is highly valued. PARTICIPANTS: Nine nurses who had at least three years working experience in relation to clinical practice participated in the study. METHODS: Semi-structured interviews and shadowing observations were the two primary methods of data collection. RESULTS: Five themes emerged: (1) building of the nurse-patient relationship, (2) provision of patient-centred care, (3) negative caring experiences, (4) professional identity, and (5) perspectives on ENP courses. CONCLUSIONS: Nurses' connection with the community led for them to a focus in their working lives. This determined their perceptions of ENP courses.

Traumatic Stress Promotes Hyperalgesia via Corticotropin-Releasing Factor-1 Receptor (CRFR1) Signaling in Central Amygdala.

Hyperalgesia is an exaggerated response to noxious stimuli produced by peripheral or central plasticity. Stress modifies nociception, and humans with post-traumatic stress disorder (PTSD) exhibit co-morbid chronic pain and amygdala dysregulation. Predator odor stress produces hyperalgesia in rodents. Systemic blockade of corticotropin-releasing factor (CRF) type 1 receptors (CRFR1s) reduces stress-induced thermal hyperalgesia. We hypothesized that CRF-CRFR1 signaling in central amygdala (CeA) mediates stress-induced hyperalgesia in rats with high stress reactivity. Adult male Wistar rats were exposed to predator odor stress in a conditioned place avoidance paradigm and indexed for high (Avoiders) and low (Non-Avoiders) avoidance of predator odor-paired context, or were unstressed Controls. Rats were tested for the latency to withdraw hindpaws from thermal stimuli (Hargreaves test). We used pharmacological, molecular, and immunohistochemical techniques to assess the role of CRF-CRFR1 signaling in CeA in stress-induced hyperalgesia. Avoiders exhibited higher CRF peptide levels in CeA that did not appear to be locally synthesized. Intra-CeA CRF infusion mimicked stress-induced hyperalgesia. Avoiders exhibited thermal hyperalgesia that was reversed by systemic or intra-CeA injection of a CRFR1 antagonist. Finally, intra-CeA infusion of tetrodotoxin produced thermal hyperalgesia in unstressed rats and blocked the anti-hyperalgesic effect of systemic CRFR1 antagonist in stressed rats. These data suggest that rats with high stress reactivity exhibit hyperalgesia that is mediated by CRF-CRFR1 signaling in CeA.

Nuclear proteomics with XRCC3 knockdown to reveal the development of doxorubicin-resistant uterine cancer.

The nucleus is a key organelle in mammary cells, which is responsible for several cellular functions including cell proliferation, gene expression, and cell survival. In addition, the nucleus is the primary targets of doxorubicin treatment. In the current study, low-abundance nuclear proteins were enriched for proteomic analysis by using a state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the nuclear protein profiling changes responsible for the development of doxorubicin resistance in human uterine cancer cells. The results of the nuclear proteomic analysis indicated that more than 2100 protein features were resolved from an equal pooled amount of three purified nuclear proteins and 117 differentially expressed spots were identified. Of these 117 identified proteins, 48 belonged to nuclear proteins and a positive correlation was observed between the expression levels of 32 of these nuclear proteins and an increase in drug resistance. According to our review of relevant research, nuclear proteins such as DNA repair protein XRCC3 (XRCC3) have not been reported to play roles in the formation of doxorubicin resistance. Previous studies have used RNA interference and cell viability analysis to evidence the essential roles of XRCC3 on its potency in the formation of doxorubicin resistance. To sum up, our nuclear proteomic approaches enabled us to identify numerous proteins, including XRCC3, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for treating doxorubicin-resistant uterine cancer.

Immunotargeting of collagenase on thrombus.

In this study, we aimed to develop a thrombus-targeting delivery system of collagenase bound to a monoclonal antibody, and to investigate the thrombolysis of an immune-conjugate in vitro and in vivo as well as the targeting effect. We prepared the immunizing conjugation of collagenase by the 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDCI) method. In order to conjugate collagenase and a monoclonal antibody, bovine serum albumin was used as a linker, increasing the number of collagenase molecules carried and keeping collagenase and the monoclonal antibody active. In vitro thrombolysis experiments showed that collagenase had a strong dissolving effect on collagen-embolus within 24 hours. We established a rabbit pulmonary embolism model to investigate the thrombolysis effect of collagenase and collagenase immunizing conjugation in vivo. Our results revealed a significant difference between collagenase and collagenase immunizing conjugation (P < 0.05). We also established a rabbit ear edge vein model to investigate the active target of collagenase immunizing conjugation. We found that collagenase immunizing conjugation had active targets, and had a strong ability to dissolve organized thrombi. In conclusion, the thrombus-targeting delivery system of collagenase we developed has active targeting effects on thrombi.

The differences of dengue vectors and human behavior between families with and without members having dengue fever/dengue hemorrhagic fever.

Dengue vectors, human knowledge and behavior have been reported to play an important role in the transmission of dengue. This study was designed to understand the differences of dengue vectors and the behavior between families with (target group) and without (control group) members having dengue fever/dengue hemorrhagic fever. Population density of dengue vectors were determined by ovitrap index. The living conditions, knowledge, and behavior related to dengue were investigated by questionnaire survey. Long-term ovitrap indices obtained in the target group was significantly higher than those obtained in the control. Most of the respondents had sufficient knowledge about the transmission and prevention of dengue. However, only low percentages of the families frequently cleaned water-filled containers and ditches around their residence, especially in the target group. These findings indicate that higher indices of dengue vectors and dengue-related behavior are important in the transmission of indigenous dengue.