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Abstract Background ArtiSential, a new articulating laparoscopic instruments, addresses the limited movement associated with conventional laparoscopic instruments. This study was conducted to assess the clinical effectiveness of ArtiSential in detailed steps of various renal surgery. Methods This study was approved by the Institutional Review Board of our institution and registered on the Clinical Research Information Service site of the Korea Disease Control and Prevention Agency. Participants meeting all inclusion and exclusion criteria were included in the clinical trial and underwent renal surgery. The clinical effectiveness of ArtiSential was assessed in terms of the feasibility and objective and subjective parameters across 9 detailed steps. Results Of the 15 potential candidates enrolled from October 2021 to November 2021, 1 patient dropped out due to anaphylaxis from an anesthetic agent, and 14 patients underwent laparoscopic surgery using ArtiSential. Of the 14 patients, 2 patients were converted to laparoscopic surgery using straight-shaped instruments due to the ischemia time exceeding 30 min, and 1 patient due to excessive bleeding. The feasibility for most steps was more than 90%, except the renorrhaphy step. The median total operation time and ischemia time were 161 and 23 min, respectively. The median estimated blood loss was 58.5 mL. Two cases of venous injury occurred during renal pedicle dissection step. The accuracy of the procedure judged by reviewers and usability judged by the operator were acceptable in all steps. The surgeon’s quantitatively measured stress score was the highest during renorrhaphy step. Conclusions Laparoscopic surgery using ArtiSential is feasible for most steps except the renorrhaphy step. The difficulty of performing renorrhaphy is attributed to prolonged ischemia time, which could be addressed by overcoming the learning curve. Trial registration Clinical Research Information Service site of the Korea Disease Control and Prevention Agency, KCT0006532. Registered 03/09/2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24071 .

Purpose: We evaluated the performance of a new multi-degree-of-freedom articulating laparoscopic instrument, ArtiSential, and compared it with that of a straight-shaped instrument and the da Vinci surgical system, in renal surgery using porcine model. Materials and Methods: Nine female Yorkshire pigs were equally divided into three groups. The three groups were compared at each surgical step in terms of objective and subjective parameters. Results: The median operative times for renal pedicle clamping and ureter dissection were significantly shorter in ArtiSential group than robotic group (1.3 min vs. 4.7 min, p=0.002; 8.1 min vs. 11.1 min, p=0.015). The median operative time for bladder repair was significantly longer in ArtiSential group than robotic and straight-shaped groups (17.9 min vs. 5.5 min, p=0.002; 17.9 min vs. 9.3 min, p=0.026). There were no significant differences among groups in terms of blood loss or intraoperative complications. ArtiSential device was less useable for renorrhaphy (p=0.009) and bladder repair (p=0.002) compared to the robotic system. ArtiSential group was less accurate than robotic group in terms of tumor resection, renorrhaphy, and bladder repair. During ureter dissection, bladder cuff excision, and bladder repair, the surgeon experienced greater wrist discomfort but lesser back discomfort in ArtiSential group than robotic group. Conclusions: For most steps, ArtiSential performed as well as robotic and straight-shaped instruments. The development of specialized surgical techniques for ArtiSential will maximize the advantages of these instruments.

Purpose: This study aimed to predict the composition of urolithiasis using deep learning from urinary stone images. Materials and Methods: We classified 1,332 stones into 31 classes according to the stone composition. The top 4 classes with a frequency of 110 or more (class 1: calcium oxalate monohydrate [COM] 100%, class 2: COM 80%+struvite 20%, class 3: COM 60%+calcium oxalate dihydrate [COD] 40%, class 4: uric acid 100%) were selected. With the 965 stone images of the top 4 classes, we used the seven convolutional neural networks (CNN) to classify urinary stones and compared their classification performances. Results: Among the seven models, Xception_Ir0.001 showed the highest accuracy, precision, and recall and was selected as the CNN model to predict the stone composition. The sensitivity and specificity for the 4 classes by Xception_Ir0.001 were as follows: class 1 (94.24%, 91.73%), class 2 (85.42%, 96.14%), class 3 (86.86%, 99.59%), and class 4 (94.96%, 98.82%). The sensitivity and specificity of the individual components of the stones were as follows. COM (98.82%, 94.96%), COD (86.86%, 99.64%), struvite (85.42%, 95.59%), and uric acid (94.96%, 98.82%). The area under the curves for class 1, 2, 3, and 4 were 0.98, 0.97, 1.00, and 1.00, respectively. Conclusions: This study showed the feasibility of deep learning for the diagnostic ability to assess urinary stone composition from images. It can be an alternative tool for conventional stone analysis and provide decision support to urologists, improving the effectiveness of diagnosis and treatment.

Purpose: To investigate the risk of symptomatic urolithiasis requiring surgical treatment according to obesity and metabolic health status using a nationwide dataset of the Korean population. Materials and Methods: Of the 5,300,646 persons who underwent health examinations between the year 2009 and 2016, within one year after the health examination, 35,137 patients who underwent surgical treatment for urolithiasis were enrolled. Participants were classified as “obese” or “non-obese” using a body mass index (BMI) cutoff of 25 kg/m2. People who developed ≥1 metabolic disease component in the index year were considered “metabolically unhealthy”, while those with none were considered “metabolically healthy”. Results: Out of 34,330 participants excluding 843 missing, 16,509 (48.1%), 4,320 (12.6%), 6,456 (18.8%), and 7,045 (20.5%) subjects were classified into the metabolically healthy non-obese (MHNO), metabolically unhealthy non-obese (MUNO), metabolically healthy obese (MHO), and metabolically unhealthy obese (MUO) group, respectively. Mean BMI was 22.1±1.9 kg/m2, 22.9±1.6 kg/m2, 26.9±1.8 kg/m2, and 27.9±2.4 kg/m2 respectively. After adjusting the age and sex, the subjects in the MUNO group had an HR (95% CI) of 1.192 (1.120–1.268), those in the MHO group, 1.242 (1.183–1.305), and those in the MUO group, 1.341 (1.278–1.407) for either extracorporeal shockwave lithotripsy or surgery, compared to those in the MHNO group. Conclusions: Metabolically healthy, obese individuals have a higher risk of developing symptomatic urolithiasis than non-obese, unhealthy, but have a lower risk than obese, unhealthy. It suggests that metabolic health and obesity have collaborative effects, independently affecting the development of symptomatic urinary stone diseases.

Purpose: This prospective, randomized, controlled study investigated the use of tamsulosin, a selective alpha-blocker, as a prophylactic medication to prevent postoperative urinary retention (POUR) following lower limb arthroplasty. Materials and Methods: The criterion for diagnosing POUR was used a postoperative bladder volume over 400 mL with incomplete emptying. Patients who underwent primary total hip or knee arthroplasty were randomly assigned at a 1:1 ratio to tamsulosin treatment and non-treatment groups at a single center from September 2018 to November 2018. The treatment group received 0.2 mg of tamsulosin orally once at night for 3 days starting on postoperative day 1. During this 3-day period, an indwelling Foley catheter was maintained. The incidence of POUR according to tamsulosin treatment following lower limb arthroplasty was the primary outcome. Results: In total, 100 patients were enrolled, of whom 5 discontinued participation. POUR was diagnosed in 20 of the remaining 95 patients (21.1%). The treatment group contained 48 patients, of whom 6 (12.5%) developed POUR, whereas POUR occurred in the 14 of the 47 patients (29.8%) in the non-treatment group. Tamsulosin treatment reduced the risk of POUR by two-thirds (odds ratio [OR], 0.337; 95% confidence interval [CI], 0.117–0.971; p=0.044). The risk reduction associated with tamsulosin treatment remained robust post-adjustment for potential covariates (OR, 0.250; 95% CI, 0.069–0.905; p=0.038). Conclusions: Tamsulosin administration immediately after lower limb arthroplasty reduced the incidence of urinary retention and diminished the need for long-term catheterization.

Abstract We evaluate the risks of various urological disorders that require treatments according to obesity and metabolic health status using a nationwide dataset of the Korean population. 3,969,788 patients who had undergone health examinations were enrolled. Participants were classified as “obese” (O) or “non-obese” (NO) using a BMI cut-off of 25 kg/m2. People who developed ≥ 1 metabolic disease component in the index year were considered “metabolically unhealthy” (MU), while those with none were considered “metabolically healthy” (MH). There were classified into the MHNO, MUNO, MHO, and MUO group. In BPH, chronic renal disease, neurogenic bladder, any medication related to voiding dysfunction, alpha-blocker, and antidiuretics, age and gender-adjusted hazard ratio (HR) was highest in MUO, but higher in MUNO than in MHO. In stress incontinence, prostate surgery, and 5alpha-reductase, HR increased in the order of MUNO, MHO, and MUO. In prostatitis, anti-incontinence surgery, and cystocele repair, HR was higher in MHO than MUNO and MUO. In cystitis, cystostomy, and anticholinergics, HR was higher in MUNO and MUO than MHO. In conclusion, obesity and metabolic health were individually or collaboratively involved in urological disorders related to voiding dysfunction. Metabolic healthy obesity needs to be distinguished in the diagnosis and treatment of urological disorders.

Purpose: To analyze the efficacy and safety of standard-dose antimuscarinic treatment on male patients with overactive bladder (OAB) symptoms showing poor efficacy after low-dose antimuscarinics. Materials and Methods: We retrospectively reviewed the data of 566 male patients aged ≥40 with OAB symptoms between January 2017 and June 2018. They were treated with low-dose antimuscarinics for at least 4 weeks and showed poor efficacy; therefore, they were switched to standard dose antimuscarinic treatment (5 mg of solifenacin) for ≥12 weeks. The international prostate symptom score (IPSS) and overactive bladder symptom score (OABSS) at baseline (V0), 4 weeks (V1), and 12 weeks (V2) were analyzed. Post void residual urine volume (PVR) was also recorded. Results: The median age, body mass index, and prostate-specific antigen levels were 69.0 years, 24.2 kg/m2, and 1.24 ng/dL, respectively. The mean value of the total IPSS and OABSS significantly decreased between V0 and V2 (from 16.73 to 13.69 and 7.33 to 5.34, respectively, all p

Purpose: To assess the possible negative health effects of human bone marrow-derived mesenchymal stem cells (hBMSCs) on fertility and early embryonic development following intracavernous injections in rats. Materials and Methods: A total of 88 Crl:CD(SD) male and female rats were equally divided into 4 groups in a random manner: control group (normal saline), low-dose group (2×105 hBMSCs), moderate-dose group (1×106 hBMSCs), and high-dose group (2×106 hBMSCs). hBMSCs or normal saline was injected into the penis of the rats 3 times at 2-week-intervals prior to mating. We compared each group with respect to parameters of reproduction and histopathology. Results: For male rats, various degrees of flushing and swelling were observed at the penile injection site in all the groups, although the severity increased in a dose-dependent manner in the hBMSC injection groups. There were no statistically significant differences in mean body weights and food consumption among all the groups of both sexes. There were no statistically significant differences in reproductive parameters among all the groups of both sexes. The absolute and relative organ weights did not significantly differ among the groups. At the time of necropsy, no remarkable findings were observed in gross examinations in all groups. On histopathological analysis, minimal mononuclear cell infiltration was observed in the right epididymis of each rat in the moderate- and high-dose groups. Conclusions: The non-toxic amount of hBMSCs for male fertility and early embryogenesis in rats under the test conditions was determined to be 2×106 cells/head.

Abstract Background We evaluated the association between serum levels of insulin‐like growth factor‐1 (IGF‐1), bioavailable testosterone, and surgical Gleason score (GS). Methods We analyzed 793 patients who underwent radical prostatectomy and 272 men with negative prostate biopsy. Serum levels of IGF‐1 and testosterone were measured before surgery or biopsy. Results The mean IGF‐1 levels of prostate cancer patients and men with a negative biopsy were 143.8 and 118.9 ng/mL, respectively (P

One hundred twenty crossbred[(Yorkshire × Landrace) × Duroc] weanling pigs (8.36 ± 1.64 kg; 21 d) were used in a 42-day trial. Pigs were randomly distributed (6 replicate pens/treatment; 5 pigs/pen) to 1 of 4 dietary treatments: 1) CON, basal diet; 2) A1, CON + antibiotic (39 ppm tiamulin); 3) BG1, basal diet + 5 g kg−1(β-glucan); and 4) BG2, basal diet + 10 g kg−1(β-glucan). On overall, average daily gain of pigs fed with A1(385 g) and BG1(388 g) was significantly higher (P

ObjectivesPostmicturition dribble (PMD) is a very common symptom in males with lower urinary tract symptoms (LUTS) worldwide, but there is no adequate questionnaire to assess it. Therefore, we developed a questionnaire named the Hallym Post Micturition Dribble Questionnaire (HPMDQ) to assess PMD, and the aim of this study is to validate it.MethodsA series of consecutive male patients newly diagnosed with LUTS and over 40 years of age who visited any of 5 medical institutions were included. LUTS were assessed in all patients using the International Prostate Symptom Score (IPSS), and PMD was assessed using the HPMDQ.ResultsIn total, 2134 male patients aged 40 to 91 years were included in this study. Of these patients, 1088 (51.0%) reported PMD. In the PMD group, the mean values for HPMDQ-Q1, HPMDQ-Q2, HPMDQ-Q3 and HPMDQ total score were 1.39, 1.10, 1.76 and 4.25, respectively. In the non-PMD group, the mean values of these scores were 0, 0.18, 1.52 and 1.58, respectively. The difference in HPMDQ scores between the 2 groups was statistically significant. PMD was significantly associated with the voiding symptoms of LUTS, prostate size and postvoid residual but not with storage symptoms.ConclusionsThe HPMDQ, which consists of 5 questions (frequency, severity, bother, quality of life and response to treatment for PMD), was developed, and its use for assessing PMD is validated in this study. It may be a useful tool for further research and in clinical practice for PMD.

N-acetylcysteine (NAC) has been used as an antioxidant to prevent oxidative cell death. However, we found NAC itself to induce neuronal death in mouse cortical cultures. Therefore, the current study was performed to investigate the mechanism of neuronal death caused by NAC. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media after 24-48 h exposure to NAC. NAC (0.1-10 mM) induced neuronal death in a concentration- and exposure time-dependent manner. However, NAC did not injure astrocytes even at a concentration of 10 mM. Also, 10 mM NAC markedly attenuated oxidative astrocyte death induced by 0.5 mM diethyl maleate or 0.25 mM H2O2. The NMDA receptor antagonist MK-801 (10 μM) markedly attenuated the neuronal death caused by 10 mM NAC, while NBQX did not affect the neuronal death. Cycloheximide (a protein synthesis inhibitor, 0.1 μg/mL) and z-VAD-FMK (a caspase inhibitor, 100 μM) also significantly attenuated neuronal death. Apoptotic features such as chromatin condensation, nuclear fragmentation, and caspase 3 activation were observed 1 h after the NAC treatment. The neuronal death induced by 1 or 10 mM NAC was significantly attenuated by the treatment with 100 μM Trolox or 1 mM ascorbic acid. NAC induced the generation of intracellular reactive oxygen species (ROS), as measured by the fluorescent dye 2',7'-dichlorofluorescein diacetate. The ROS generation was almost completely abolished by treatment with Trolox or ascorbic acid. These findings demonstrate that NAC can cause oxidative, apoptotic, and excitotoxic neuronal death in mouse neuronal cultures. [ABSTRACT FROM AUTHOR]

We examined the effect of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on neuronal viability in mouse cortical near-pure neuronal cultures. Addition of fluoxetine to the media for 24 hours induced neuronal death in a concentration- dependent manner. To delineate the mechanisms of fluoxetine-induced neuronal death, we investigated the effects of trolox, cycloheximide (CHX), BDNF, z-VAD-FMK, and various metal-chelators on fluoxetine-induced neuronal death. Neuronal death was assessed by MTT assay. The addition of 20 μM fluoxetine to the media for 24 hours induced 60-70% neuronal death, which was associated with the hallmarks of apoptosis, chromatin condensation and DNA laddering. Fluoxetine-induced death was significantly attenuated by CHX, BDNF, or z-VAD-FMK. Treatment with antioxidants, trolox and ascorbate, also markedly attenuated fluoxetine-induced death. Interestingly, some divalent cation chelators (EGTA, Ca-EDTA, and Zn-EDTA) also markedly attenuated the neurotoxicity. Fluoxetine-induced reactive oxygen species (ROS) generation was measured using the fluorescent dye 2',7'-dichlorofluorescin diacetate. Trolox and bathocuproine disulfonic acid (BCPS), a cell membrane impermeable copper ion chelator, markedly attenuated the ROS production and neuronal death. However, deferoxamine, an iron chelator, did not affect ROS generation or neurotoxicity. We examined the changes in intracellular copper concentration using a copper-selective fluorescent dye, Phen Green FL, which is quenched by free copper ions. Fluoxetine quenched the fluorescence in neuronal cells, and the quenching effect of fluoxetine was reversed by co-treatment with BCPS, however, not by deferoxamine. These findings demonstrate that fluoxetine could induce apoptotic and oxidative neuronal death associated with an influx of copper ions. [ABSTRACT FROM AUTHOR]

The Amyloid β peptide (Aβ) is a main component of senile plaques in Alzheimer's disease. Currently, NADPH oxidase (NOX) and mitochondria are considered as primary sources of ROS induced by Aβ. However, the contribution of NOX and mitochondria to Aβ-induced ROS generation has not been well defined. To delineate the relative involvement of NOX and mitochondria in Aβ-induced ROS generation and neuronal death in mouse cortical cultures, we examined the effect of NOX inhibitors, apocynin and AEBSF, and the mitochondria-targeted antioxidants (MTAs), mitotempol and mitoquinone, on Aβ-induced ROS generation and neuronal deaths. Cell death was assessed by measuring lactate dehydrogenase efflux in bathing media at 24 and 48 hrs after exposure to Aβ1-42. Aβ1-42 induced dose- and time-dependent neuronal deaths in cortical cultures. Treatment with 20 μM Aβ1-42 markedly and continuously increased not only the DHE fluorescence (intracellular ROS signal), but also the DHR123 fluorescence (mitochondrial ROS signal) up to 8 hrs. Treatment with apocynin or AEBSF selectively suppressed the increase in DHE fluorescence, while treatment with mitotempol selectively suppressed the increase in DHR123 fluorescence. Each treatment with apocynin, AEBSF, mitotempol or mitoquinone significantly attenuated the Aβ1-42-induced neuronal deaths. However, any combined treatment with apocynin/AEBSF and mitotempol/mitoquinone failed to show additive effects. These findings indicate that 20 μM Aβ1-42 induces oxidative neuronal death via inducing mitochondrial ROS as well as NOX activation in mixed cortical cultures, but combined suppression of intracellular and mitochondrial ROS generation fail to show any additive neuroprotective effects against Aβ neurotoxicity. [ABSTRACT FROM AUTHOR]

Most normal cells express L-type amino acid transporter 2 (LAT2). However, L-type amino acid transporter 1 (LAT1) is highly expressed in many tumor cells and presumed to support their increased growth and proliferation. This study examined the effects of JPH203, a selective LAT1 inhibitor, on cell growth and its mechanism for cell death in Saos2 human osteosarcoma cells. FOB human osteoblastic cells and Saos2 cells expressed LAT1 and LAT2 together with their associating protein 4F2 heavy chain, but the expression of LAT2 in the Saos2 cells was especially weak. JPH203 and BCH, a non-selective L-type amino acid transporter inhibitor, potently inhibited L-leucine uptake in Saos2 cells. As expected, the intrinsic ability of JPH203 to inhibit L-leucine uptake was far more efficient than that of BCH in Saos2 cells. Likewise, JPH203 and BCH inhibited Saos2 cell growth with JPH203 being superior to BCH in this regard. Furthermore, JPH203 increased apoptosis rates and formed DNA ladder in Saos2 cells. Moreover, JPH203 activated the mitochondria-dependent apoptotic signaling pathway by upregulating pro-apoptotic factors, such as Bad, Bax, and Bak, and the active form of caspase-9, and downregulating anti-apoptotic factors, such as Bcl-2 and Bcl-xL. These results suggest that the inhibition of LAT1 activity via JPH203, which may act as a potential novel anti-cancer agent, leads to apoptosis mediated by the mitochondria-dependent intrinsic apoptotic signaling pathway by inducing the intracellular depletion of neutral amino acids essential for cell growth in Saos2 human osteosarcoma cells. [ABSTRACT FROM AUTHOR]

β-Amyloid peptide (Aβ) is the main component of senile plaques in patients with Alzheimer's disease, and is known to be a main pathogenic factor of the disease. Recent evidence indicates that activation of NADPH oxidase (NOX) in microglia or astrocytes may be a source of Aβ-induced reactive oxygen species (ROS). We investigated the role of neuronal NOX in Aβ-induced neuronal death in mouse mixed cortical cultures. Cell death was assessed by measuring lactate dehydrogenase efflux to bathing media 24 or 48 hr after exposure to Aβ25-35, a fragment of Aβ with an equivalent neurotoxic effect. Aβ25-35 induced neuronal death in concentration- and time- dependent manners with apoptotic features. Neuronal death was significantly attenuated, not only by anti-apoptotic drugs, such as z-VAD-fmk and cycloheximide, but also by antioxidants, such as trolox, ascorbic acid, and epigallocatethin gallate. We also demonstrated that treatment with 20 μM Aβ25-35 increased fluorescent signals in mixed cortical cultures, but produced only weak signals in pure astrocyte cultures in the presence of 2′,7′-dichlorofluorescin diacetate (DCF-DA), an indicator for intracellular ROS. Increased DCF-DA fluorescence was markedly inhibited, not only by trolox, but also by selective NOX inhibitors, such as apocynin and AEBSF. Western blot analyses revealed that Aβ25-35 increased the expression of gp91phox, a main subunit of NOX in cells. The above antioxidants, apocynin, and AEBSF significantly attenuated neuronal death induced by Aβ25-35. Furthermore, the gp91phox-specific siRNA-based knockdown of NOX significantly inhibited neuronal death. These results suggest that activation of neuronal NOX is involved in Aβ25-35-induced neuronal death. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the clinical and radiological outcomes of double-bundle anterior cruciate ligament (ACL) reconstruction using an outside-in technique with a follow-up of two- to six-years, especially in terms of the sports activity level and radiological degeneration. Materials and Methods: Sixty-seven patients who were available for a minimum two-year follow-up after double-bundle ACL reconstruction using an outside-in technique were retrospectively evaluated. The mean follow-up period was 43.7 months. The knee function and stability were evaluated before the operation, one year after the operation (short-term follow-up), and more than two years after the operation (last follow-up). Results: Regarding the knee function, the Lysholm score, International Knee Documentation Committee (IKDC) evaluation, and hop test showed significant improvement. Regarding the stability, the Lachman test, pivot shift test, KT-2000 arthrometer data, and anterior drawer radiographs using Telos showed significant improvement. Regarding the sports activity level, the patients who returned to pre-injury level activity was 68.7% according to the Tegner activity score and 76.1% according to the Cincinnati sports activity scale score. The incidence of aggravated degeneration or development of greater than IKDC grade A degeneration after surgery was 10.4%. Conclusions: Double-bundle ACL reconstruction using an outside-in technique showed favorable clinical and radiological outcomes with respect to the knee function and stability, joint degeneraion, and, especially, return to pre-injury sports activity. [ABSTRACT FROM AUTHOR]

Objects: Tuberous sclerosis complex (TSC) is a dysgenetic syndrome involved in multiple organs, and the pathognomonic cortical tuber act as an epileptic substrate. The amino acid transport system L (LAT) is a major nutrient transport system, and LAT1 is highly expressed in malignant tumors to support tumor cell growth. To study the life-long epilepsy from the cortical tuber, the expression of LAT1 in balloon cells and dysplastic neurons of the cortical tuber is investigated. Materials and methods: LAT1 expression was investigated by LAT1 mRNA using reverse transcription-polymerase chain reaction and immunohistochemical staining with anti-human LAT1 antibody in nine patients with TSC and three control brains. Conclusion: LAT1 mRNA was detectable only in fresh-frozen tissues of TSC, and it was upregulated in the cortical tuber lesion. While the LAT1 immunopositivity of control brains was limited in the capillary endothelial cells in the gray matter, increased LAT1 immunopositivity was noted in balloon cells of the cortical tubers in addition to the capillary endothelial cells as shown in control brains. Linear and strong immunopositivity along the cell membrane and cytoplasm of the balloon cells, and weakly granular immunopositivity in their cytoplasm were noted. Increased expression of LAT1 in the balloon cells is important for the active transport of large neutral amino acids into the balloon cells, and that the biologic process may play an important role in the active protein synthesis with metabolic maintenance of balloon cells in cortical tubers of patients with TSC. [ABSTRACT FROM AUTHOR]

The transcription of neuron-specific genes must be repressed in nonneuronal cells. REST/NRSF is a transcription factor that restricts the expression of many neuronal genes through interaction with the neuron-restrictive silencer element at the promoter level. PAHX-AP1 is a neuronal gene that is developmentally up-regulated in the adult mouse brain but that has no functional NRSE motif in its 5′ upstream sequence. Here, we report that the transcription factor AP4 and the corepressor geminin form a functional complex in which SMRT and histone deacetylase 3 are recruited. The functional complex represses PAHX-AP1 expression in nonneuronal cells and participates in regulating the developmental expression of PAHX-AP1 in the brain. This complex also serves as a transcriptional repressor of DYRKIA, a candidate gene for Down's syndrome. Furthermore, compared with that in normal fetal brain, the expression of AP4 and geminin is reduced in Down's syndrome fetal brain at 20 weeks of gestation age, at which time premature overexpression of dual-specificity tyrosine-phosphorylated and regulated kinase 1A (DYRK1A) is observed. Our findings indicate that AP4 and geminin act as a previously undescribed repressor complex distinct from REST/NRSF to negatively regulate the expression of target genes in nonneuronal cells and suggest that the AP4-geminin complex may contribute to suppressing the precocious expression of target genes in fetal brain. [ABSTRACT FROM AUTHOR]

Although the vanilloid receptor 1 (VR1) was originally discovered on primary sensory neurons, its broad tissue expression in non-neuronal cells has been reported on. Recently, VR1 expression was clearly demonstrated in a variety of cutaneous components, such as keratinocytes, glandular epithelium, mast cells and sebocytes, except for melanocytes and fibroblasts. However, we demonstrated the VR1 expression in the cultured human skin fibroblasts as follows. Previously cloned human VR1 primers that corresponded to the expected size of 680 bp by reverse transcriptase polymerase chain reaction were identified on the fibroblasts, the same as was noted for the positive control, the HaCaT cells. A positive immunoreactivity of the VR1 was observed both on fibroblasts and on HaCaT cells by Western blotting analysis. Fibroblasts treated with capsaicin, an agonist to the VR1, induced significant changes of the membrane current and the intracellular calcium level, and these changes were antagonized by capsazepin. Capsaicin treatment also showed a positive immunocytochemistry result. Our results suggest the existence of VR1 on fibroblasts; this receptor is likely to be influenced by ligand-dependent activation. [ABSTRACT FROM AUTHOR]

We examined the effect of ginseng total saponins (GTS) on phosphoinositide metabolism stimulated by activation of muscarinic receptor using rat cortical cultures. Carbachol stimulated formation of [³H]inositol phosphates ([³H]InsPs) by 3.3-fold over basal level in [³H]inositolprelabeled cells. Pretreatment of GTS inhibited formation of [³H]InsPs evoked by carbachol by 70%-90%. Addition of GTS alone had no effect on the basal formation of [³H]InsPs. The inhibitory effect of the GTS on carbachol-stimulated formation of [³H]InsPs was dose- and time-dependent. IC[sub 50] was 6.0 ± 2.8 µg/ml. We also examined the effect of GTS on [³H]InsP[sub 1], [³H]InsP[sub 2], or [³H]InsP[sub 3] formation evoked by carbachol. Although GTS had no effect on the basal [³H]InsP[sub 1], [³H]InsP[sub 2], or [³H]InsP[sub 3] formation, pretreatment of GTS inhibited [³H]InsP[sub 1], [³H]InsP[sub 2], or [³H]InsP[sub 3] formation evoked by carbachol, respectively. Addition of individual ginsenosides such as ginsenoside Rb[sub 1], Rc, Rd, Re, or Rg[sub 2] had no effect on the basal formation of [³H]InsPs, whereas pretreatment of ginsenoside Rb[sub 2], Rc, Rd, Re, Rf, Rg[sub 1] or Rg[sub 2] inhibited formation of [³H]InsPs evoked by carbachol by 79%-89%. The results suggest that the inhibitory effect of GTS and its individual ginsenosides on carbachol-stimulated formation of [³H]InsPs in cortical neurons could be one pharmacological action of Panax ginseng. [ABSTRACT FROM AUTHOR]

Abstract Background Achieving consistent accuracy in radiographic measurements across different equipment and protocols is challenging. This study evaluates an advanced deep learning (DL) model, building upon a precursor, for its proficiency in generating uniform and precise alignment measurements in full-leg radiographs irrespective of institutional imaging differences. Methods The enhanced DL model was trained on over 10,000 radiographs. Utilizing a segmented approach, it separately identified and evaluated regions of interest (ROIs) for the hip, knee, and ankle, subsequently integrating these regions. For external validation, 300 datasets from three distinct institutes with varied imaging protocols and equipment were employed. The study measured seven radiologic parameters: hip-knee-ankle angle, lateral distal femoral angle, medial proximal tibial angle, joint line convergence angle, weight-bearing line ratio, joint line obliquity angle, and lateral distal tibial angle. Measurements by the model were compared with an orthopedic specialist's evaluations using inter-observer and intra-observer intraclass correlation coefficients (ICCs). Additionally, the absolute error percentage in alignment measurements was assessed, and the processing duration for radiograph evaluation was recorded. Results The DL model exhibited excellent performance, achieving an inter-observer ICC between 0.936 and 0.997, on par with an orthopedic specialist, and an intra-observer ICC of 1.000. The model's consistency was robust across different institutional imaging protocols. Its accuracy was particularly notable in measuring the hip-knee-ankle angle, with no instances of absolute error exceeding 1.5 degrees. The enhanced model significantly improved processing speed, reducing the time by 30-fold from an initial 10–11 s to 300 ms. Conclusions The enhanced DL model demonstrated its ability for accurate, rapid alignment measurements in full-leg radiographs, regardless of protocol variations, signifying its potential for broad clinical and research applicability.

Gemifloxacin, a broad-spectrum antibacterial agent of the fluoroquinolone class, is used to treat bacterial infections, including acute bacterial exacerbation of chronic bronchitis and community-acquired pneumonia. This study aimed to develop a simple and robust analysis of gemifloxacin in human plasma by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). The sample was prepared using simple protein precipitation procedures with acetonitrile and separated using the Gemini C18 column with a mobile phase (0.1% formic acid: 0.1% formic acid in acetonitrile = 78: 22 (V/V)). Moxifloxacin was used as an internal standard. The mass spectrometer was operated in the positive ion mode using multiple reaction monitoring. Each precursor ion of gemifloxacin and moxifloxacin was monitored at m/z 390.1/402.1, and their product ions were monitored at m/z 372.3/384.4. The calibration curve showed linearity in 0.005–5 μg/mL with an appropriate correlation coefficient (≥0.99). The variation coefficient of intra- and interprecision values of gemifloxacin was

Although a bioabsorbable bone hemostatic agent (BBHA) was developed approximately 20 years ago to overcome the shortcomings of conventional bone wax, its bleeding control capacity has not yet been studied. This study was aimed at investigating the efficacy and safety of BBHA in total knee arthroplasty (TKA). Sixty-two patients who underwent unilateral primary TKA for knee osteoarthritis were included and randomized to the control or BBHA group. Before releasing the tourniquet, BBHA was applied on the bone-cut surface that was not covered by implants. The primary variable was the drainage volume during the postoperative period. The secondary outcomes were total estimated blood loss (EBL), hemoglobin level, hematocrit level, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, range of motion (ROM), pain visual analog scale (VAS) score, and rate of complications. There were no significant differences in drainage volume or EBL between the 2 groups. Hemoglobin and hematocrit levels were higher in the BBHA group during the 4-week postoperative period; however, the intergroup differences were not significant. The ESR, CRP, ROM, and pain VAS scores in the BBHA group were not significantly different from the corresponding values in the control group. No specific complications were observed. Although BBHA was found to be safe without complications, it did not decrease bleeding after TKA in general cases. Further studies are necessary to evaluate the efficacy of BBHA in patients with coagulation problems.