Intraoperative monitoring of trigeminal neuralgia: a technical note.

Trigeminal neuralgia causes excruciating pain in patients. Microvascular decompression is indicated for drug-resistant s trigeminal neuralgia. Unlike facial spasms, any part of the nerve can be the culprit, not only the root entry zone. Intraoperative monitoring does not yet exist for trigeminal neuralgia. We successfully used intermittent stimulation of the superior cerebellar artery during surgery and confirmed the disappearance of the trigeminal nerve motor branch reaction after the release of the compression. Intermittent direct stimulation of the culprit blood vessel using the motor branch of the trigeminal nerve may assist in intraoperative monitoring of decompression during trigeminal nerve vascular decompression surgery.

Evaluation of fecal DNA extraction protocols for human gut microbiome studies.

BACKGROUND: DNA extraction is an important factor influencing the microbiome profile in fecal samples. Considering that the QIAamp DNA Stool Mini Kit, one of the most commonly used DNA extraction kits, is no longer manufactured, this study aimed to investigate whether a new commercially available kit, the QIAamp PowerFecal Pro DNA Kit, yields comparable microbiome profiles with those previously obtained using the QIAamp DNA Stool Mini Kit. RESULTS: We extracted DNA from fecal samples of 10 individuals using three protocols (protocol P of the QIAamp PowerFecal Pro DNA Kit, and protocols SB and S of the QIAamp DNA Stool Mini Kit with and without an additional bead-beating step, respectively) in triplicate. Ninety extracted DNA samples were subjected to 16S rRNA gene sequencing. DNA quality measured by 260/280 absorbance ratios was found to be optimal in protocol P. Additionally, the DNA quantity and microbiome diversity obtained using protocol P were significantly higher than those of protocol S, however, did not differ significantly from those of protocol SB. Based on the overall microbiome profiles, variations between protocol P and protocol SB or S were significantly less than between-individual variations. Furthermore, most genera were not differentially abundant in protocol P compared to the other protocols, and the number of differentially abundant genera, as well as the degree of fold-changes were smaller between protocols P and SB than between protocols P and S. CONCLUSIONS: The QIAamp PowerFecal Pro DNA Kit exhibited microbiome analysis results that were comparable with those of the QIAamp DNA Stool Mini Kit with a bead-beating step. These results will prove useful for researchers investigating the gut microbiome in selecting an alternative protocol to the widely used but discontinued kit.

Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals.

Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynamics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatography. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 µg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 µg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when administered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment.

SNARE-Mediated Fusion of Single Chromaffin Granules with Pore-Spanning Membranes.

Pore-spanning membranes (PSMs) composed of supported membrane parts as well as freestanding membrane parts are shown to be very versatile to investigate SNARE-mediated fusion on the single-particle level. They provide a planar geometry readily accessible by confocal fluorescence microscopy, which enabled us for the first time, to our knowledge, to investigate the fusion of individual natural secretory granules (i.e., chromaffin granules (CGs)) on the single-particle level by two-color fluorescence microscopy in a time-resolved manner. The t-SNARE acceptor complex ΔN49 was reconstituted into PSMs containing 2 mol % 1,2-dipalmitoyl-sn-glycero-3-phosphatidylinositol-4,5-bisphosphate and Atto488-1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine, and CGs were fluorescently labeled with 2-((1E,3E)-5-((Z)-3,3-dimethyl-1-octadecylindolin-2-ylidene)penta-1,3-dien-1-yl)-3,3-dimethyl-1-octadecyl-3H-indol-1-ium perchlorate. We compared the dynamics of docked and hemifused CGs as well as their fusion efficacy and kinetics with the results obtained for synthetic synaptobrevin 2-doped vesicles fusing with PSMs of the same composition. Whereas the synthetic vesicles were fully immobile on supported PSMs, docked as well as hemifused CGs were mobile on both PSM parts, which suggests that this system resembles more closely the natural situation. The fusion process of CGs proceeded through three-dimensional post-lipid-mixing structures, which were readily resolved on the gold-covered pore rims of the PSMs and which are discussed in the context of intermediate states observed in live cells.

Randomized control trial comparing the effect of cilostazol and aspirin on changes in carotid intima-medial thickness.

Antiplatelet drugs are effective in preventing recurrence of atherosclerosis in type 2 diabetes (T2D) patients. However, the efficacy and usefulness of antiplatelet drugs on the progression of carotid intima-media thickness (IMT), a marker for evaluating early atherosclerotic vascular disease, has not been analyzed. We conducted a prospective, randomized, open, 36-month trial comparing cilostazol vs. aspirin. A total of 415 T2D patients (age range 38-83 years; 206 females) without macrovascular complications were randomized to either an aspirin (100 mg/day) or cilostazol (200 mg/day) treatment. Patients underwent B-mode ultrasonography annually to assess the IMT and serum levels of inflammatory markers were measured before and after each treatment. Potential confounders were statistically adjusted, and included lipid profiles, HbA1c, body mass index, waist circumference, anti-hypertensive and statin medications. The decrease in mean left, maximum left, mean right and maximum right IMT were significantly greater with cilostazol compared with aspirin (- 0.094 ± 0.186 mm vs. 0.006 ± 0.220 mm, p < 0.001; - 0.080 ± 0.214 mm vs. 0.040 ± 0.264 mm, p < 0.001; - 0.064 ± 0.183 mm vs. 0.004 ± 0.203 mm, p = 0.015; - 0.058 ± 0.225 mm vs. 0.023 ± 0.248 mm, p = 0.022, respectively). And these differences remained significant after adjustment of potential confounders. Compared with aspirin, cilostazol treatment was associated with significantly increased HDL cholesterol (p = 0.039) and 25-hydroxy vitamin D levels (p = 0.001). Cilostazol treatment was associated with significantly lowered IMT in T2D patients compared to aspirin, independent of conventional cardiovascular risk factors. Cilostazol may inhibit plaque formation and have beneficial effects on atherosclerosis through vasodilatory and antiplatelet effects.

Long-term effects on glycaemic control and ß-cell preservation of early intensive treatment in patients with newly diagnosed type 2 diabetes: A multicentre randomized trial.

AIM: To determine the effects of early intensive glycaemic control with intensive insulin treatment (IIT) or initial combined oral antidiabetic drug (COAD) therapy on long-term glycaemic control and the preservation of ß-cell function in people with type 2 diabetes mellitus (T2DM). METHODS: Newly diagnosed drug-naïve patients with T2DM from 8 outpatient diabetes centres were randomized to receive either IIT (n = 50; glargine/glulisine) or COAD (n = 47; glimepiride/metformin) as intensive treatment until the termination criteria to ensure euglycaemia were met. After intensive treatment, the patients completed a follow-up period with either lifestyle modification (LSM) alone or rescue therapy to maintain target glycated haemoglobin levels of <7% (53 mmol/mol) up to week 104. The primary outcomes were analysed after excluding participants who were anti-glutamic acid decarboxylase autoantibody-positive. RESULTS: Both intensive treatment methods were effective for short-term glycaemic control, but improvements in the disposition index (DI) were significantly greater in the IIT group than in the COAD group (P = .021). During the follow-up period after intensive treatment, the two groups significantly differed in rescue method regarding the maintenance of comparable levels of glycaemic control (P = .010) and more participants who received IIT exhibited well-controlled glycaemia with LSM alone. Additionally, the IIT group maintained a higher DI than the COAD group during the follow-up period. Cox regression analysis showed that the IIT method was associated with a 52.5% lower risk of failing to maintain drug-free glycaemic remission compared with the COAD method (P = .015). CONCLUSIONS: The findings indicate that outpatient clinic-based IIT to ensure euglycaemia in newly diagnosed patients with T2DM might be an effective initial therapeutic option for improvements in ß-cell function and glycaemic control over the long term, without serious adverse events.

Clinical heterogeneity of type 1 diabetes (T1D) found in Asia.

Diabetes mellitus among young patients in Asia is caused by a complex set of factors. Although type 1 diabetes (T1D) remains the most common form of diabetes in children, the recent unabated increase in obesity has resulted in the emergence of type 2 diabetes (T2D) as a new type of diabetes among adolescents and young adults. In addition to the typical autoimmune type 1 diabetes (T1aD) and T2D patients, there is a variable incidence of cases of non-autoimmune types of T1D associated with insulin deficiency (T1bD). Additional forms have been described, including fulminant T1D (FT1D). Although most diagnoses of T1D are classified as T1aD, fulminant T1D exists as a hyper-acute subtype of T1D that affects older children, without associated autoimmunity. Patient with this rare aetiology of diabetes showed a complete loss of ß-cell secretory capacity without evidence of recovery, necessitating long-term treatment with insulin. In addition, latent autoimmune diabetes in adults is a form of autoimmune-mediated diabetes, usually diagnosed during the insulin-dependent stage that follows a non-insulin requiring phase, which can be diagnosed earlier based on anti-islet autoantibody positivity. Some reports discuss T1bD. Others are elaborating on the presence of "atypical T1b diabetes," such as Flatbush diabetes. The prevalence of diabetes mellitus in young adults continues to rise in Asian populations as T2D increases. With improved characterization of patients with diabetes, the range of diabetic subgroups will become even more diverse in the future. Distinguishing T1D, T2D, and other forms of diabetes in young patients is challenging in Asian populations, as the correct diagnosis is clinically important and has implications for prognosis and management. Despite aetiological heterogeneity in the usual clinical setting, early diagnosis and classification of patients with diabetes relying on clinical grounds as well as measuring islet autoantibodies and fasting plasma C-peptide could provide a possible viable method to minimize complications.

The Role of ERK1/2 in the Development of Diabetic Cardiomyopathy.

Diabetes mellitus is a chronic metabolic condition that affects carbohydrate, lipid and protein metabolism and may impair numerous organs and functions of the organism. Cardiac dysfunction afflicts many patients who experience the oxidative stress of the heart. Diabetic cardiomyopathy (DCM) is one of the major complications that accounts for more than half of diabetes-related morbidity and mortality cases. Chronic hyperglycemia and hyperlipidemia from diabetes mellitus cause cardiac oxidative stress, endothelial dysfunction, impaired cellular calcium handling, mitochondrial dysfunction, metabolic disturbances, and remodeling of the extracellular matrix, which ultimately lead to DCM. Although many studies have explored the mechanisms leading to DCM, the pathophysiology of DCM has not yet been fully clarified. In fact, as a potential mechanism, the associations between DCM development and mitogen-activated protein kinase (MAPK) activation have been the subjects of tremendous interest. Nonetheless, much remains to be investigated, such as tissue- and cell-specific processes of selection of MAPK activation between pro-apoptotic vs. pro-survival fate, as well as their relation with the pathogenesis of diabetes and associated complications. In general, it turns out that MAPK signaling pathways, such as extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 MAP kinase, are demonstrated to be actively involved in myocardial dysfunction, hypertrophy, fibrosis and heart failure. As one of MAPK family members, the activation of ERK1/2 has also been known to be involved in cardiac hypertrophy and dysfunction. However, many recent studies have demonstrated that ERK1/2 signaling activation also plays a crucial role in FGF21 signaling and exerts a protective environment of glucose and lipid metabolism, therefore preventing abnormal healing and cardiac dysfunction. The duration, extent, and subcellular compartment of ERK1/2 activation are vital to differential biological effects of ERK1/2. Moreover, many intracellular events, including mitochondrial signaling and protein kinases, manipulate signaling upstream and downstream of MAPK, to influence myocardial survival or death. In this review, we will summarize the roles of ERK1/2 pathways in DCM development by the evidence from current studies and will present novel opinions on "differential influence of ERK1/2 action in cardiac dysfunction, and protection against myocardial ischemia-reperfusion injury".

Serological Detection of Borrelia burgdorferi among Horses in Korea.

Lyme disease is a tick-borne zoonotic infectious disease caused by Borrelia burgdorferi. The present study assessed the infection status of B. burgdorferi among horses reared in Korea using ELISA and PCR. Between 2009 and 2013, blood samples were collected from 727 horses throughout Korea. Data for each animal including age, gender, breed, and region of sample collection were used for epidemiological analysis. Overall, 38 (5.2%; true prevalence: 5.5%) of 727 horses were seropositive by ELISA. There were statistically significant differences according to breed and region (P<0.001) whose differences might be attributed to the ecology of vector ticks and climate conditions. Using 2 nested PCR, none of the samples tested positive for B. burgdorferi. Thus, a positive ELISA result can indicate only that the tested horse was previously exposed to B. burgdorferi, with no certainty over the time of exposure. Since global warming is likely to increase the abundance of ticks in Korea, continuous monitoring of tick-borne diseases in Korean horses is needed.

Relationship between Single Nucleotide Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Gene and Fatty Acid Composition in Korean Native Cattle.

The peroxisome proliferator-activated receptor gamma (PPARγ) gene plays an important role in the biosynthesis process controlled by a number of fatty acid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the PPARγ gene and the fatty acid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fatty acid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fatty acids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the PPARγ gene affected fatty acid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle.

Molecular Basis of the Membrane Interaction of the ß2e Subunit of Voltage-Gated Ca(2+) Channels.

The auxiliary ß subunit plays an important role in the regulation of voltage-gated calcium (CaV) channels. Recently, it was revealed that ß2e associates with the plasma membrane through an electrostatic interaction between N-terminal basic residues and anionic phospholipids. However, a molecular-level understanding of ß-subunit membrane recruitment in structural detail has remained elusive. In this study, using a combination of site-directed mutagenesis, liposome-binding assays, and multiscale molecular-dynamics (MD) simulation, we developed a physical model of how the ß2e subunit is recruited electrostatically to the plasma membrane. In a fluorescence resonance energy transfer assay with liposomes, binding of the N-terminal peptide (23 residues) to liposome was significantly increased in the presence of phosphatidylserine (PS) and phosphatidylinositol 4,5-bisphosphate (PIP2). A mutagenesis analysis suggested that two basic residues proximal to Met-1, Lys-2 (K2) and Trp-5 (W5), are more important for membrane binding of the ß2e subunit than distal residues from the N-terminus. Our MD simulations revealed that a stretched binding mode of the N-terminus to PS is required for stable membrane attachment through polar and nonpolar interactions. This mode obtained from MD simulations is consistent with experimental results showing that K2A, W5A, and K2A/W5A mutants failed to be targeted to the plasma membrane. We also investigated the effects of a mutated ß2e subunit on inactivation kinetics and regulation of CaV channels by PIP2. In experiments with voltage-sensing phosphatase (VSP), a double mutation in the N-terminus of ß2e (K2A/W5A) increased the PIP2 sensitivity of CaV2.2 and CaV1.3 channels by ∼3-fold compared with wild-type ß2e subunit. Together, our results suggest that membrane targeting of the ß2e subunit is initiated from the nonspecific electrostatic insertion of N-terminal K2 and W5 residues into the membrane. The PS-ß2e interaction observed here provides a molecular insight into general principles for protein binding to the plasma membrane, as well as the regulatory roles of phospholipids in transporters and ion channels.

α-SNAP interferes with the zippering of the SNARE protein membrane fusion machinery.

Neuronal exocytosis is mediated by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Before fusion, SNARE proteins form complexes bridging the membrane followed by assembly toward the C-terminal membrane anchors, thus initiating membrane fusion. After fusion, the SNARE complex is disassembled by the AAA-ATPase N-ethylmaleimide-sensitive factor that requires the cofactor α-SNAP to first bind to the assembled SNARE complex. Using chromaffin granules and liposomes we now show that α-SNAP on its own interferes with the zippering of membrane-anchored SNARE complexes midway through the zippering reaction, arresting SNAREs in a partially assembled trans-complex and preventing fusion. Intriguingly, the interference does not result in an inhibitory effect on synaptic vesicles, suggesting that membrane properties also influence the final outcome of α-SNAP interference with SNARE zippering. We suggest that binding of α-SNAP to the SNARE complex affects the ability of the SNARE complex to harness energy or transmit force to the membrane.

Intracellular membrane association of the Aplysia cAMP phosphodiesterase long and short forms via different targeting mechanisms.

Phosphodiesterases (PDEs) play key roles in cAMP compartmentalization, which is required for intracellular signaling processes, through specific subcellular targeting. Previously, we showed that the long and short forms of Aplysia PDE4 (ApPDE4), which are localized to the membranes of distinct subcellular organelles, play key roles in 5-hydroxytryptamine-induced synaptic facilitation in Aplysia sensory and motor synapses. However, the molecular mechanism of the isoform-specific distinct membrane targeting was not clear. In this study, we further investigated the molecular mechanism of the membrane targeting of the ApPDE4 long and short forms. We found that the membrane targeting of the long form was mediated by hydrophobic interactions, mainly via 16 amino acids at the N-terminal region, whereas the short form was targeted solely to the plasma membrane, mainly by nonspecific electrostatic interactions between their N termini and the negatively charged lipids such as the phosphatidylinositol polyphosphates PI4P and PI(4,5)P2, which are embedded in the inner leaflet of the plasma membrane. Moreover, oligomerization of the long or short form by interaction of their respective upstream conserved region domains, UCR1 and UCR2, enhanced their plasma membrane targeting. These results suggest that the long and short forms of ApPDE4 are distinctly targeted to intracellular membranes through their direct association with the membranes via hydrophobic and electrostatic interactions, respectively.

Identification of exonic nucleotide variants of the thyroid hormone responsive protein gene associated with carcass traits and Fatty Acid composition in korean cattle.

The thyroid hormone responsive protein (THRSP) gene is a functional gene that can be used to indicate the fatty acid compositions. This study investigates the relationships of exonic single nucleotide polymorphisms (SNPs) in the THRSP gene and fatty acid composition of muscle fat and marbling score in the 612 Korean cattle. The relationships between fatty acid composition and eight SNPs in the THRSP gene (g.78 G>A, g.173 C>T, g.184 C>T, g.190 C>A, g.194 C>T, g.277 C>G, g.283 T>G and g.290 T>G) were investigated, and according to the results, two SNPs (g.78 G>A and g.184 C>T) in exon 1 were associated with fatty acid composition. The GG and CC genotypes of g.78 G>A and g.184 C>T had higher unsaturated fatty acid (UFA) and monounsaturated fatty acid (MUFA) content (p<0.05). In addition, the ht1*ht1 group (Val/Ala haplotype) in a linkage disequilibrium increased MUFAs and marbling scores for carcass traits (p<0.05). As a result, g.78 G>A and g.184 C>T had significantly relationships with UFAs and MUFAs. Two SNPs in the THRSP gene affected fatty acid composition, suggesting that GG and CC genotypes and the ht1*ht1 group (Val/Ala haplotype) can be markers to genetically improve the quality and flavor of beef.

Correlation between low skeletal muscle index and 3D anthropometric data measured by 3D body scanner: screening sarcopenia.

Background: The screening tools for sarcopenia are measuring calf circumference, SARC-F or SPPB. However, not all of these tools have high sensitivity, specificity, and low margins of error. This research investigates potential of 3D anthropometry of the lower extremities on screening of sarcopenia. Methods: From October 2022 to February 2023, we retrospectively analyzed results of 3D body scanner and bio-impedance analysis for patients aged 45 to 85 at risk of sarcopenia. The 3D scanner measured the surface and volume values of both thighs and calves. When skeletal muscle index (SMI) is less than 5.7, patients were classified to Low SMI group, indicative of sarcopenia. Results: A total six out of 62 patients were classified to Low SMI group, showing significantly lower values of right, left, mean calf volumes and mean calf surface than the other patients (right calf volume 2.62 L vs. 3.34 L, p = 0.033; left calf volume 2.62 L vs. 3.25 L, p = 0.044; mean calf volume 2.62 L vs. 3.29 L, p = 0.029; mean calf surface 0.12 m2 vs. 0.13 m2, p = 0.049). There was no statistical difference in thigh volume and surface. Through AUC-ROC analysis, mean calf volume was the most significant cut-off value (right calf volume 2.80 L, AUC = 0.768; left calf volume 2.75 L, AUC = 0.753; mean calf volume 3.06 L, AUC = 0.774; mean calf surface 0.12 m2, AUC = 0.747). Conclusion: The calf volume and surface values have significant relationship with low SMI, and the mean calf volume was the most significant cut-off screening value for Low SMI. The 3D scanner demonstrated its value as a new means for screening sarcopenia.

Characteristics of tire-road wear particles (TRWPs) and road pavement wear particles (RPWPs) generated through a novel tire abrasion simulator based on real road pavement conditions.

Microparticles such as tire-road wear particles (TRWPs) and road pavement wear particles (RPWPs) are generated by the friction between tire tread and road surface. TRWPs and RPWPs on roads are dispersed through traffic and transferred to rivers and seas via runoff to accumulate in sediments. However, research on the generation of both TRWP and RPWP has rarely been conducted. In this study, the generation of both TRWP and RPWP was investigated using a novel tire abrasion simulator equipped with paved road and bus tire, and their contributions to the generation of microparticles were examined. Two types of model paved roads, asphalt and concrete pavements (AP and CP, respectively), were applied. TRWPs generated from the simulator exhibited morphologies very similar to those on real roads. The abrasion rate for the CP was 2.8 times higher than that for the AP. The wear particle size distributions peaked at the size ranges of 63-106 µm and 212-500 µm for the AP and CP, respectively. Totals of 84 wt% and 89 wt% of the wear particles were distributed in size ranges of 38-212 µm for the AP and 106-1000 µm for the CP. The tire wear particle (TWP) contents in the total wear particles of 38-500 µm were 21.7 wt% and 30.0 wt% for the AP and CP, respectively, and decreased as the particle size decreased. The weight of RPWP was higher than that of TWP in TRWP. Contributions from road pavement to the generation of wear particles of 38-500 µm were 3.6 and 2.3 times higher than those from tire tread for the AP and CP, respectively, and the contribution increased as the wear particle size decreased.

Improving Facial Fat Graft Survival Using Stromal Vascular Fraction-Enriched Lipotransfer: A Multicenter Randomized Controlled Study.

BACKGROUND: Although previous clinical studies have reported that cell-assisted lipotransfer increases the fat survival rate in facial fat transplants, most were case studies without quantitative evaluation. A multicenter randomized controlled study was performed to evaluate the safety and efficacy of the stromal vascular fraction (SVF) in facial fat grafts. METHODS: Twenty-three participants were enrolled for autologous fat transfer in the face, and assigned randomly to the experimental ( n = 11) or control ( n = 12) group. Fat survival was assessed using magnetic resonance imaging at 6 and 24 weeks postoperatively. Subjective evaluations were performed by the patients and surgeons. To address safety concerns, results of an SVF culture and the postoperative complications were recorded. RESULTS: The overall fat survival rate was significantly higher in the experimental group than in the control group (6 weeks, 74.5% ± 9.99% versus 66.55% ± 13.77%, P < 0.025; 24 weeks, 71.27% ± 10.43% versus 61.98% ± 13.46%, P < 0.012). Specifically, graft survival in the forehead was 12.82% higher in the experimental group when compared with that in the control group at 6 weeks ( P < 0.023). Furthermore, graft survival in the forehead ( P < 0.021) and cheeks ( P < 0.035) was superior in the experimental group at 24 weeks. At 24 weeks, the aesthetic scores given by the surgeons were higher in the experimental group than in the control group ( P < 0.03); however, no significant intergroup differences were noted in the patient-evaluated scores. Neither bacterial growth from SVF cultures nor postoperative complications were noted. CONCLUSION: SVF enrichment for autologous fat grafting can be a safe and effective technique for increasing the fat retention rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Giant skull base periosteal chondroma treated with endonasal endoscopic surgery: illustrative case.

BACKGROUND: Intracranial chondroma is an extremely rare type of tumor composed of mature hyaline cartilaginous tissues. No previous cases of skull base periosteal chondroma have been presented. OBSERVATIONS: A 31-year-old male had progressive memory loss and diminished motivation for the previous 1.5 years. Magnetic resonance imaging revealed a giant tumor with partial calcification arising from the upper clivus and extending to the prepontine cistern. Compression of the brainstem and hypothalamus was significant. Surgery was performed and intentionally limited to an intracapsular resection with endoscopic endonasal surgery (EES), and the brainstem and hypothalamus were successfully decompressed. Pathological examination findings showed a composition of hyaline cartilage with chondrocyte clusters. Genetic testing with next-generation sequencing indicated alternations in IDH1 R132C, KDR Q472H, IDH2 I142L, and TP53 P72R. On the basis of these findings, a diagnosis of periosteal chondroma was made. Postoperatively, complete relief from all symptoms was noted, and MRI one year later showed no evidence of tumor regrowth. LESSONS: This is the first known report of skull base periosteal chondroma. Genetic testing was useful for confirming the diagnosis, and EES was effective for treatment. Should such a tumor show adhesion to an important structure, an intracapsular excision can be beneficial for avoiding complications.

PIP2 Is An Electrostatic Catalyst for Vesicle Fusion by Lowering the Hydration Energy: Arresting Vesicle Fusion by Masking PIP2.

Lipids are key factors in regulating membrane fusion. Lipids are not only structural components to form membranes but also active catalysts for vesicle fusion and neurotransmitter release, which are driven by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. SNARE proteins seem to be partially assembled before fusion, but the mechanisms that arrest vesicle fusion before Ca2+ influx are still not clear. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP2) electrostatically triggers vesicle fusion as an electrostatic catalyst by lowering the hydration energy and that a myristoylated alanine-rich C-kinase substrate (MARCKS), a PIP2-binding protein, arrests vesicle fusion in a vesicle docking state where the SNARE complex is partially assembled. Vesicle-mimicking liposomes fail to reproduce vesicle fusion arrest by masking PIP2, indicating that native vesicles are essential for the reconstitution of physiological vesicle fusion. PIP2 attracts cations to repel water molecules from membranes, thus lowering the hydration energy barrier.

Intradermal Inoculation of Inactivated Foot-and-Mouth Disease Vaccine Induced Effective Immune Responses Comparable to Conventional Intramuscular Injection in Pigs.

All pigs in the Republic of Korea are given the foot-and-mouth disease virus (FMDV) vaccine intramuscularly (IM) as part of the country's vaccination policy. However, the IM administration of the FMDV vaccine to pig results in residual vaccine components in the muscle and undesirable changes in muscle and soft tissues, causing economic losses in swine production. In this study, we evaluated whether intradermal (ID) vaccination could be proposed as an alternative to IM administration. ID vaccination (0.2 mL on each side of the neck muscle) and IM vaccination (2 mL on each side of the neck muscle) were performed twice, separated by 14 days, using a commercial FMD vaccine in specific-pathogen-free pigs. We observed growth performance, gross and microscopic lesions at the inoculation site, FMDV-specific antibodies, and neutralizing antibodies for 35 days after vaccination. Side effects on the skin grossly appeared following ID administration, but most were reduced within two weeks. All ID-vaccinated pigs showed inflammatory lesions limited to the dermis, but IM-vaccinated pigs had abnormal undesirable changes and pus in the muscle. ID-vaccinated pigs performed comparably to IM-vaccinated pigs in terms of growth, FMD virus-specific antibodies, protection capability against FMDV, and T-cell induction. This study demonstrated that the ID inoculation of the inactivated FMD vaccine induced immune responses comparable to an IM injection at 1/10 of the inoculation dose and that the inoculation lesion was limited to the dermis, effectively protecting against the formation of abnormal undesirable changes in muscle and soft tissues.