Versatile nanobody-based approach to image, track and reconstitute functional Neurexin-1 in vivo.

Neurexins are key adhesion proteins that coordinate extracellular and intracellular synaptic components. Nonetheless, the low abundance of these multidomain proteins has complicated any localization and structure-function studies. Here we combine an ALFA tag (AT)/nanobody (NbALFA) tool with classic genetics, cell biology and electrophysiology to examine the distribution and function of the Drosophila Nrx-1 in vivo. We generate full-length and ΔPDZ ALFA-tagged Nrx-1 variants and find that the PDZ binding motif is key to Nrx-1 surface expression. A PDZ binding motif provided in trans, via genetically encoded cytosolic NbALFA-PDZ chimera, fully restores the synaptic localization and function of NrxΔPDZ-AT. Using cytosolic NbALFA-mScarlet intrabody, we achieve compartment-specific detection of endogenous Nrx-1, track live Nrx-1 transport along the motor neuron axons, and demonstrate that Nrx-1 co-migrates with Rab2-positive vesicles. Our findings illustrate the versatility of the ALFA system and pave the way towards dissecting functional domains of complex proteins in vivo.

Investigating demic versus cultural diffusion and sex bias in the spread of Austronesian languages in Vietnam.

Austronesian (AN) is the second-largest language family in the world, particularly widespread in Island Southeast Asia (ISEA) and Oceania. In Mainland Southeast Asia (MSEA), groups speaking these languages are concentrated in the highlands of Vietnam. However, our knowledge of the spread of AN-speaking populations in MSEA remains limited; in particular, it is not clear if AN languages were spread by demic or cultural diffusion. In this study, we present and analyze new data consisting of complete mitogenomes from 369 individuals and 847 Y-chromosomal single nucleotide polymorphisms (SNPs) from 170 individuals from all five Vietnamese Austronesian groups (VN-AN) and five neighboring Vietnamese Austroasiatic groups (VN-AA). We found genetic signals consistent with matrilocality in some, but not all, of the VN-AN groups. Population affinity analyses indicated connections between the AN-speaking Giarai and certain Taiwanese AN groups (Rukai, Paiwan, and Bunun). However, overall, there were closer genetic affinities between VN-AN groups and neighboring VN-AA groups, suggesting language shifts. Our study provides insights into the genetic structure of AN-speaking communities in MSEA, characterized by some contact with Taiwan and language shift in neighboring groups, indicating that the expansion of AN speakers in MSEA was a combination of cultural and demic diffusion.

A theoretical study of the oxidation of benzene by manganese oxide clusters: formation of quinone intermediates.

Manganese oxides (MnxOy) have been widely applied in various chemical industrial processes owing to their long lifetime, low cost and high abundance. They have been used as co-reactants for the elimination of volatile organic compounds (VOCs); however, their oxidation mechanism is not clearly established. In this theoretical study, interaction capacities between benzene (C6H6) and MnxOy clusters, which were modeled with MnO2 and Mn2O3 molecules, were investigated by quantum chemical computations using density functional theory (DFT) with the PBE-D3 functional. The interaction capacity between C6H6 and MnxOy was evaluated, and the probing of the initial stage of the C6H6 oxidation at a molecular level offers an in-depth oxidation reaction path. Interaction energies computed in several spin states, along with the analysis of the electron distribution using the quantum theory of atoms in molecules, natural bond orbital and Wiberg bond index techniques as well as local softness values and MO energies of fragments, point out that the interaction between C6H6 and Mn2O3 is stronger than that with MnO2, amounting to -43 and -35 kcal mol-1, respectively, and the metal atom is identified as the primary active site. During the oxide cluster-assisted oxidation, benzene firstly undergoes an oxidation reaction by active oxygen to generate intermediates such as hydroquinone and benzoquinone. The pathway involving p-benzoquinone as the product (noted as PR1) is the most energetically favored one through a transition structure lying at 19 kcal mol-1, below the energy reference of the reactants, leading to an energy barrier significantly lower than that of 36 kcal mol-1 found for the gas phase oxidation reaction with molecular oxygen without the assistance of the oxide clusters. Potential energy profiles illustrating the reaction paths and molecular mechanisms were described in detail.

Low-dose computed tomography scan and biopsy for assessing lung cancer prevalence and related factors in high-risk populations.

Background: Lung cancer is the second most diagnosed cancer and the leading cause of cancer death in 2020, representing approximately one in 10 (11.4 %) cancers diagnosed and one in 5 (18.0 %) deaths. There are currently very few studies evaluating the prevalence and related factors of lung cancer detected using low-dose CT scans. Objective: Evaluate the prevalence and related factors of lung cancer using low-dose CT scans in high-risk populations in Vietnam. Materials and methods: A cross-sectional analysis study of 169 high-risk patients was conducted to assess the lung cancer prevalence and related factors. Enrolled patients received a physical examination, low-dose computerized tomography scan, and biopsy if abnormalities were found through the CT scan. Univariable and Multivariable analysis through Odd Ratio (OR) to assess the related risk of lung cancer. Results: A total of 169 high-risk patients with a mean age of 62.93 ± 9.31 (years), and the majority were male (91.7 %). Of which 4 cases (2.37 %) were recorded with lung cancer, 3 cases of adenocarcinoma, and 1 case of squamous cell carcinoma. A history of smoking and Chronic Obstructive Pulmonary Disease (COPD) were associated with an increased risk of abnormalities on lung CT scans. Multivariate regression analysis revealed that smoking over 30 pack-years and COPD significantly increased the risk of abnormalities on lung CT scans, p < 0.05.100 % of lung cancer-detected cases were male and smoking ≥30 pack - years. Conclusion: The prevalence of lung cancer in the Vietnamese high-risk population was relatively high. Relative factors such as smoking ≥30 pack - years, and COPD had increased risk of CTscan abnormalities.

Unveiling Fall Triggers in Older Adults: A Machine Learning Graphical Model Analysis.

While existing research has identified diverse fall risk factors in adults aged 60 and older across various areas, comprehensively examining the interrelationships between all factors can enhance our knowledge of complex mechanisms and ultimately prevent falls. This study employs a novel approach-a mixed undirected graphical model (MUGM)-to unravel the interplay between sociodemographics, mental well-being, body composition, self-assessed and performance-based fall risk assessments, and physical activity patterns. Using a parameterized joint probability density, MUGMs specify the higher-order dependence structure and reveals the underlying graphical structure of heterogeneous variables. The MUGM consisting of mixed types of variables (continuous and categorical) has versatile applications that provide innovative and practical insights, as it is equipped to transcend the limitations of traditional correlation analysis and uncover sophisticated interactions within a high-dimensional data set. Our study included 120 elders from central Florida whose 37 fall risk factors were analyzed using an MUGM. Among the identified features, 34 exhibited pairwise relationships, while COVID-19-related factors and housing composition remained conditionally independent from all others. The results from our study serve as a foundational exploration, and future research investigating the longitudinal aspects of these features plays a pivotal role in enhancing our knowledge of the dynamics contributing to fall prevention in this population.

scRNA-seq data from the larval Drosophila ventral cord provides a resource for studying motor systems function and development.

The Drosophila larval ventral nerve cord (VNC) shares many similarities with the spinal cord of vertebrates and has emerged as a major model for understanding the development and function of motor systems. Here, we use high-quality scRNA-seq, validated by anatomical identification, to create a comprehensive census of larval VNC cell types. We show that the neural lineages that comprise the adult VNC are already defined, but quiescent, at the larval stage. Using fluorescence-activated cell sorting (FACS)-enriched populations, we separate all motor neuron bundles and link individual neuron clusters to morphologically characterized known subtypes. We discovered a glutamate receptor subunit required for basal neurotransmission and homeostasis at the larval neuromuscular junction. We describe larval glia and endorse the general view that glia perform consistent activities throughout development. This census represents an extensive resource and a powerful platform for future discoveries of cellular and molecular mechanisms in repair, regeneration, plasticity, homeostasis, and behavioral coordination.

Selective striatal fast-spiking interneuron inhibition induces cortical seizure.

Whether striatal fast-spiking interneurons are involved in cortical synchronization remains elusive. We performed acute microinjections of a selective FSI-AMPA receptor antagonist into the sensorimotor striatum of non-human primates to verify whether selective FSI inhibition within the sensorimotor striatum could potentially modify cortical excitability, thereby triggering focal seizures. Experiments were performed on three fascicularis monkeys. During each experimental session, low volumes of IEM-1460 (4-8 µL) were injected slowly at 1 µL/min. Spontaneous behavioral changes were classified according to the Racine scale modified for primates. These induced motor behaviors were correlated with electroencephalographic (EEG and EMG) measures. Power spectrum and time-frequency analysis were performed and compared between each period of interest. Pharmacological selective inhibition of striatal fast-spiking INs induced focal motor seizures. Back averaging confirmed that myoclonic activity was closely linked to cortical spikes-and-waves epileptic activity, with a significant increase in cortical EEG power in all studied frequency bands (p < .0001). Thus, striatal FSIs likely play a role in controlling cortical excitability through the cortico-striato-thalamo-cortical pathway. They may contribute to the pathophysiology of focal motor epilepsies by modulating the threshold at which focal motor seizures are triggered.

Vocal fingerprinting reveals a substantially smaller global population of the Critically Endangered cao vit gibbon (Nomascus nasutus) than previously thought.

The cao vit gibbon (Nomascus nasutus) is one of the rarest primates on Earth and now only survives in a single forest patch of less than 5000 ha on the Vietnam-China border. Accurate monitoring of the last remaining population is critical to inform ongoing conservation interventions and track conservation success over time. However, traditional methods for monitoring gibbons, involving triangulation of groups from their songs, are inherently subjective and likely subject to considerable measurement errors. To overcome this, we aimed to use 'vocal fingerprinting' to distinguish the different singing males in the population. During the 2021 population survey, we complemented the traditional observations made by survey teams with a concurrent passive acoustic monitoring array. Counts of gibbon group sizes were also assisted with a UAV-mounted thermal camera. After identifying eight family groups in the acoustic data and incorporating long-term data, we estimate that the population was comprised of 74 individuals in 11 family groups, which is 38% smaller than previously thought. We have no evidence that the population has declined-indeed it appears to be growing, with new groups having formed in recent years-and the difference is instead due to double-counting of groups in previous surveys employing the triangulation method. Indeed, using spatially explicit capture-recapture modelling, we uncovered substantial measurement error in the bearings and distances from field teams. We also applied semi- and fully-automatic approaches to clustering the male calls into groups, finding no evidence that we had missed any males with the manual approach. Given the very small size of the population, conservation actions are now even more urgent, in particular habitat restoration to allow the population to expand. Our new population estimate now serves as a more robust basis for informing management actions and tracking conservation success over time.

Avian influenza A(H5) virus circulation in live bird markets in Vietnam, 2017-2022.

BACKGROUND: Highly pathogenic avian influenza A(H5) human infections are a global concern, with many A(H5) human cases detected in Vietnam, including a case in October 2022. Using avian influenza virus surveillance from March 2017-September 2022, we described the percent of pooled samples that were positive for avian influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses in live bird markets (LBMs) in Vietnam. METHODS: Monthly at each LBM, 30 poultry oropharyngeal swab specimens and five environmental samples were collected. Samples were pooled in groups of five and tested for influenza A, A(H5), A(H5N1), A(H5N6), and A(H5N8) viruses by real-time reverse-transcription polymerase chain reaction. Trends in the percent of pooled samples that were positive for avian influenza were summarized by LBM characteristics and time and compared with the number of passively detected avian influenza outbreaks using Spearman's rank correlation. RESULTS: A total of 25,774 pooled samples were collected through active surveillance at 167 LBMs in 24 provinces; 36.9% of pooled samples were positive for influenza A, 3.6% A(H5), 1.9% A(H5N1), 1.1% A(H5N6), and 0.2% A(H5N8). Influenza A(H5) viruses were identified January-December and at least once in 91.7% of sampled provinces. In 246 A(H5) outbreaks in poultry; 20.3% were influenza A(H5N1), 60.2% A(H5N6), and 19.5% A(H5N8); outbreaks did not correlate with active surveillance. CONCLUSIONS: In Vietnam, influenza A(H5) viruses were detected by active surveillance in LBMs year-round and in most provinces sampled. In addition to outbreak reporting, active surveillance for A(H5) viruses in settings with high potential for animal-to-human spillover can provide situational awareness.

Measuring the impact of an integrated bite case management program on the detection of canine rabies cases in Vietnam.

Introduction: Dog-mediated rabies is enzootic in Vietnam, resulting in at least 70 reported human deaths and 500,000 human rabies exposures annually. In 2016, an integrated bite cases management (IBCM) based surveillance program was developed to improve knowledge of the dog-mediated rabies burden in Phu Tho Province of Vietnam. Methods: The Vietnam Animal Rabies Surveillance Program (VARSP) was established in four stages: (1) Laboratory development, (2) Training of community One Health workers, (3) Paper-based-reporting (VARSP 1.0), and (4) Electronic case reporting (VARSP 2.0). Investigation and diagnostic data collected from March 2016 to December 2019 were compared with historical records of animal rabies cases dating back to January 2012. A risk analysis was conducted to evaluate the probability of a rabies exposure resulting in death after a dog bite, based on data collected over the course of an IBCM investigation. Results: Prior to the implementation of VARSP, between 2012 and 2015, there was an average of one rabies investigation per year, resulting in two confirmed and two probable animal rabies cases. During the 46 months that VARSP was operational (2016 - 2019), 1048 animal investigations were conducted, which identified 79 (8%) laboratory-confirmed rabies cases and 233 (22%) clinically-confirmed(probable) cases. VARSP produced a 78-fold increase in annual animal rabies case detection (one cases detected per year pre-VARSP vs 78 cases per year under VARSP). The risk of succumbing to rabies for bite victims of apparently healthy dogs available for home quarantine, was three deaths for every 10,000 untreated exposures. Discussion: A pilot IBCM model used in Phu Tho Province showed promising results for improving rabies surveillance, with a 26-fold increase in annual case detection after implementation of a One Health model. The risk for a person bitten by an apparently healthy dog to develop rabies in the absence of rabies PEP was very low, which supports the WHO recommendations to delay PEP for this category of bite victims, when trained animal assessors are available and routinely communicate with the medical sector. Recent adoption of an electronic IBCM system is likely to expedite adoption of VARSP 2.0 to other Provinces and improve accuracy of field decisions and data collection.

Optic foramen location on computed tomography.

BACKGROUND: This study aimed to identify the location of the optic foramen in relation to the anterior sphenoid sinus wall, which is essential information for surgeons in planning and performing endoscopic transnasal surgery. METHODS: Computed tomography scans of 200 orbits from 100 adult patients with no abnormalities were examined. The results included the location of the optic foramen in relation to the anterior sphenoid sinus wall and the distance between them, as well as the distance from the optic foramen and the anterior sphenoid sinus wall to the carotid prominence in the posterior sphenoid sinus. RESULTS: The optic foramen was anterior to the anterior sphenoid sinus wall in 48.5% of orbits, and posterior in the remaining 51.5%. The mean distance from the optic foramen to the anterior sphenoid sinus wall was 3.82 ± 1.25 mm. The mean distances from the optic foramen and the anterior sphenoid sinus wall to the carotid prominence were 7.67 ± 1.73 and 7.95 ± 2.53 mm, respectively. CONCLUSION: The optic foramen was anterior to the anterior wall of the sphenoid sinus in approximately half of the orbits examined in this study, and posterior in the remaining half. The mean distance from the optic foramen to the anterior sphenoid sinus wall of the sphenoid sinus was 3.82 ± 1.25 mm.

Outbreak of Sexually Transmitted Nongroupable Neisseria meningitidis-Associated Urethritis, Vietnam.

We report on an outbreak of nongroupable Neisseria meningitidis-associated urethritis, primarily among men who have sex with men in southern Vietnam. Nearly 50% of N. meningitidis isolates were resistant to ciprofloxacin. This emerging pathogen should be considered in the differential diagnosis and management of urethritis.

Evaluating a unique enhanced recovery protocol in laparoscopic donor nephrectomy: A single center experience.

INTRODUCTION: Enhanced recovery after surgery (ERAS) protocols have been associated with a reduction in opioid consumption and a hastening in recovery in abdominal surgery. However, their impact on laparoscopic donor nephrectomy (LDN) has not been fully elucidated. The aim of this study is to evaluate opioid consumption and other relevant outcome measures before and after implementation of a unique LDN ERAS protocol. METHODS: 244 LDN patients were included in this retrospective cohort study. Forty-six underwent LDN prior to implementation of ERAS, whereas 198 patients received ERAS perioperative care. The primary outcome was daily oral morphine equivalent (OME) consumption averaged over the entire postoperative stay. Due to removal of preoperative oral morphine from the protocol partway through the study period, the ERAS group was further subdivided into morphine recipients and non-recipients for subgroup analysis. Secondary outcomes included the incidence of postoperative nausea and vomiting (PONV), length of stay, pain scores, and other relevant measures. RESULTS: ERAS donors consumed significantly fewer average daily OMEs than Pre-ERAS donors (21.5 vs. 37.6, respectively; p < .0001). There were no statistically significant differences in OME consumption between morphine recipients and non-recipients. The ERAS group experienced less PONV (44.4% requiring one or more rescue antiemetic postoperatively, vs. 60.9% of Pre-ERAS donors; p = .008). CONCLUSIONS: A protocol pairing lidocaine and ketamine with a comprehensive approach to preoperative PO intake, premedication, intraoperative fluid management and postoperative pain control is associated with reduced opioid consumption in LDN.

Quantitative Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) Imaging of Individual Vesicles to Investigate the Relation between Fraction of Chemical Release and Vesicle Size.

We used correlative transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to quantify the contents of subvesicular compartments, and to measure the partial release fraction of 13 C-dopamine in cellular nanovesicles as a function of size. Three modes of exocytosis comprise full release, kiss-and-run, and partial release. The latter has been subject to scientific debate, despite a growing amount of supporting literature. We tailored culturing procedures to alter vesicle size and definitively show no size correlation with the fraction of partial release. In NanoSIMS images, vesicle content was indicated by the presence of isotopic dopamine, while vesicles which underwent partial release were identified by the presence of an 127 I-labelled drug, to which they were exposed during exocytosis allowing entry into the open vesicle prior to its closing again. Demonstration of similar partial release fractions indicates that this mode of exocytosis is predominant across a wide range of vesicle sizes.

Interactions between Paracetamol and Formaldehyde: Theoretical Investigation and Topological Analysis.

In this work, noncovalent interactions including hydrogen bonds, C···C, N···O, and van der Waals forces between paracetamol and formaldehyde were investigated using the second-order perturbation theory MP2 in conjunction with the correlation consistent basis sets (aug-cc-pVDZ and aug-cc-pVTZ). Two molecular conformations of paracetamol were considered. Seven equilibrium geometries of dimers were found from the result of the interactions with formaldehyde for each conformation of paracetamol. Interaction energies of complexes with both ZPE and BSSE corrections range from -7.0 to -21.7 kJ mol-1. Topological parameters (such as electron density, its Laplacian, and local electron energy density at the bond critical points) of the bonds from atoms in molecules theory were analyzed in detail. The natural bond orbital analysis showed that the stability of complexes was controlled by noncovalent interactions including O-H···O, N-H···O, C-H···O, C-H···N, C-H···H-C, C···C, and N···O. The red- and blue-shifted hydrogen bonds could both be observed in these complexes. The properties of these interactions were also further examined in water using a polarized continuum model. In water, the stability of the complex was slightly reduced as compared to that in the gas phase.

Characterization of Stress Granule Protein Turnover in Neuronal Progenitor Cells Using Correlative STED and NanoSIMS Imaging.

Stress granules (SGs) are stress-induced biomolecular condensates which originate primarily from inactivated RNA translation machinery and translation initiation factors. SG formation is an important defensive mechanism for cell survival, while its dysfunction has been linked to neurodegenerative diseases. However, the molecular mechanisms of SG assembly and disassembly, as well as their impacts on cellular recovery, are not fully understood. More thorough investigations into the molecular dynamics of SG pathways are required to understand the pathophysiological roles of SGs in cellular systems. Here, we characterize the SG and cytoplasmic protein turnover in neuronal progenitor cells (NPCs) under stressed and non-stressed conditions using correlative STED and NanoSIMS imaging. We incubate NPCs with isotopically labelled (15N) leucine and stress them with the ER stressor thapsigargin (TG). A correlation of STED and NanoSIMS allows the localization of individual SGs (using STED), and their protein turnover can then be extracted based on the 15N/14N ratio (using NanoSIMS). We found that TG-induced SGs, which are highly dynamic domains, recruit their constituents predominantly from the cytoplasm. Moreover, ER stress impairs the total cellular protein turnover regimen, and this impairment is not restored after the commonly proceeded stress recovery period.

A 36-Year-Old Woman with Acute Liver Failure Following Acetaminophen Overdose, Raised INR of 8.7, and Normal Blood Viscosity Measured by Rotational Thromboelastometry (ROTEM).

BACKGROUND Fulminant hepatic failure (FHF) is commonly associated with elevated prothrombin time (PT) and international normalized ratio (INR). There is a commensurate decline in pro- and anti-hemostatic factors, and hemostatic function is rebalanced, not reflected in INR. This report presents the case of a 36-year-old woman with FHF following acetaminophen overdose, an increased INR above 8.7, and normal blood viscosity measured by rotational thromboelastometry (ROTEM). CASE REPORT A 36-year-old woman presented with FHF following an acetaminophen overdose. On arrival, she was lethargic but arousable and followed commands. Her King's College Criteria for acetaminophen toxicity was 2 and her MELD score was 36. Her INR was unmeasurably high (>8.7). To evaluate whole-blood coagulation, a ROTEM analysis was performed. All parameters (CT, CFT, alpha-angle, A10, MCF) of the NATEM were within reference range. Despite the normal ROTEM, spontaneous bleeding was a concern. The patient received 5 units of cryoprecipitate and 9 units of FFP prior to a central venous line placement. She was started on molecular adsorbent recirculating system and continuous veno-venous hemodialysis, but died on day 7. CONCLUSIONS Patients with FHF can have normal whole-blood coagulation based on ROTEM even if INR levels are unmeasurably high. Viscoelastic tests such as ROTEM, which assesses whole-blood coagulation properties, are preferrable for coagulation monitoring in these patients. Blood product transfusion to correct coagulation abnormality, like FFP and cryoprecipitate, may be used based on the result of viscoelastic testing over conventional coagulation testing.

Carriage of Plasmid-Mediated Colistin Resistance-1-Positive Escherichia coli in Humans, Animals, and Environment on Farms in Vietnam.

Plasmid-Mediated Colistin Resistance 1 (mcr-1) was first reported in 2015 and is a great concern to human health. In this study, we investigated the prevalence of mcr-1 and mcr-1-positive Escherichia coli (MCRPEC) and the association in infection status among various reservoirs connected to livestock. The study was conducted in 70 poultry and swine farms in a commune in Ha Nam province, northern Vietnam. Samples were collected from farmers, food animals, domestic animals, and farm environments (flies and wastewater) for polymerase chain reaction (PCR) screening for mcr-1 gene and species identification of PCR positive isolates. Among 379 obtained mcr-1 positives isolates, Escherichia coli was the major identified, varying from 50% (2/4) in dog feces to 100% (31/31) in humans feces isolates. The prevalence of MCRPEC was 14.4% (20/139), 49.7% (96/193), 31.3% (25/80), 36.7% (40/109), 26.9% (18/67), and 3.9% (2/51) in humans, chickens, pigs, flies, wastewater, and dogs, respectively. The study identified association between MCRPEC infection status in humans and flies (OR = 3.4), between flies and chickens (OR = 5.3), and between flies and pigs (OR = 9.0). Farmers' age and farm livestock unit were also associated factors of MCRPEC infection status in humans (OR = 5.1 and 1.05, respectively). These findings bring new knowledge on antibiotic resistance in livestock setting and important suggestions on potential role of flies in the transmission of mcr-1 resistance gene.

Bony Cartilaginous Graft in Unilateral Cleft Lip Rhinoplasty.

BACKGROUND: Cleft rhinoplasty is a challenging form of nasal correction of both esthetic and functional deformities. The septal cartilage in many Asian patients are not sufficient and weak. Does a combination of the septal cartilage and the bony septum have both esthetic and functional benefits to secondary unilateral cleft rhinoplasty? PATIENTS AND METHODS: Thirty patients with a unilateral cleft lip palate underwent open rhinoplasty from October 2018 to January 2021. After preserving a 10 mm L-strut, the posterior cartilaginous and bony septum were harvested as an integrative unit. The osteocartilaginous graft was used as a caudal septal extension graft and an extended spreader graft. Correcting the asymmetry of the tip and tip projection followed. The intraoperative harvested composite graft was analyzed. Acoustic rhinometry and the 3-dimensional anthropometric measurements of the external nose were assessed before and after surgery. RESULTS: The osteocartilaginous unit was much larger than the cartilaginous part of this unit. The mean nasal tip height and the nasolabial angle increased significantly after surgery. The measurement of cross-sectional areas and volumes by acoustic rhinometry revealed that septorhinoplasty provided a significant increase in the function of both nasal cavities. CONCLUSIONS: This septal bony cartilaginous graft is effective for cleft lip nasal deformity when correcting the deviated septum, creating a supporting frame to correct the nasal tip asymmetry, improving function.

Visualization of Partial Exocytotic Content Release and Chemical Transport into Nanovesicles in Cells.

For decades, "all-or-none" and "kiss-and-run" were thought to be the only major exocytotic release modes in cell-to-cell communication, while the significance of partial release has not yet been widely recognized and accepted owing to the lack of direct evidence for exocytotic partial release. Correlative imaging with transmission electron microscopy and NanoSIMS imaging and a dual stable isotope labeling approach was used to study the cargo status of vesicles before and after exocytosis; demonstrating a measurable loss of transmitter in individual vesicles following stimulation due to partial release. Model secretory cells were incubated with 13C-labeled l-3,4-dihydroxyphenylalanine, resulting in the loading of 13C-labeled dopamine into their vesicles. A second label, di-N-desethylamiodarone, having the stable isotope 127I, was introduced during stimulation. A significant drop in the level of 13C-labeled dopamine and a reduction in vesicle size, with an increasing level of 127I-, was observed in vesicles of stimulated cells. Colocalization of 13C and 127I- in several vesicles was observed after stimulation. Thus, chemical visualization shows transient opening of vesicles to the exterior of the cell without full release the dopamine cargo. We present a direct calculation for the fraction of neurotransmitter release from combined imaging data. The average vesicular release is 60% of the total catecholamine. An important observation is that extracellular molecules can be introduced to cells during the partial exocytotic release process. This nonendocytic transport process appears to be a general route of entry that might be exploited pharmacologically.