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The potential risks associated with organs from COVID-19-infected donors were unclear. To determine the SARS-CoV-2 infection status of corneas transplanted during the COVID-19 pandemic, we performed a polymerase chain reaction (PCR) using the corneal preservation solution that was used for corneal transplantation. We also examined the postoperative health status of the recipients. This study included 144 transplants in 143 eyes. Ninety-nine eyes of imported corneas and 10 of the 14 corneas donated in the prefecture were PCR tested at our hospital, and all were SARS-CoV-2 negative. All corneal transplants were performed after confirming their SARS-CoV-2 negativity by a PCR using a corneal preservation solution at our hospital or a nasopharyngeal swab at a previous facility. Despite postoperative steroid administration, no patient developed COVID-19 infection until discharge. Hence, if the donor's nasopharyngeal swab test is SARS-CoV-2 negative, COVID-19 infection in the recipient due to corneal transplantation may be prevented. Since corneal transplant recipients are susceptible to infection due to prolonged steroid administration and are at high risk for severe diseases if infection occurs, SARS-CoV-2 detection testing using nasopharyngeal swabs in donors should be performed. [ABSTRACT FROM AUTHOR]

Retinitis pigmentosa (RP) and macular dystrophy (MD) cause severe retinal dysfunction, affecting 1 in 4000 people worldwide. This disease is currently assumed to be intractable, because effective therapeutic methods have not been established, regardless of genetic or sporadic traits. Here, we examined a RP mouse model in which the Prominin-1 (Prom1) gene was deficient and investigated the molecular events occurring at the outset of retinal dysfunction. We extracted the Prom1-deficient retina subjected to light exposure for a short time, conducted single-cell expression profiling, and compared the gene expression with and without stimuli. We identified the cells and genes whose expression levels change directly in response to light stimuli. Among the genes altered by light stimulation, Igf1 was decreased in rod photoreceptor cells and astrocytes under the light-stimulated condition. Consistently, the insulin-like growth factor (IGF) signal was weakened in light-stimulated photoreceptor cells. The recovery of Igf1 expression with the adeno-associated virus (AAV) prevented photoreceptor cell death, and its treatment in combination with the endothelin receptor antagonist led to the blockade of abnormal glial activation and the promotion of glycolysis, thereby resulting in the improvement of retinal functions, as assayed by electroretinography. We additionally demonstrated that the attenuation of mammalian/mechanistic target of rapamycin (mTOR), which mediates IGF signalling, leads to complications in maintaining retinal homeostasis. Together, we propose that combinatorial manipulation of distinct mechanisms is useful for the maintenance of the retinal condition. [ABSTRACT FROM AUTHOR]

Introduction: Immune checkpoint inhibitors (ICIs) have significantly improved the prognosis of non-small cell lung cancer (NSCLC). However, only a limited proportion of patients can benefit from this therapy, and clinically useful predictive biomarkers remain to be elucidated. Methods: Blood was collected from 189 patients with NSCLC before and six weeks after the initiation of ICI treatment (anti-PD-1 or anti-PD-L1 antibody). Soluble PD-1 (sPD-1) and PD-L1 (sPD-L1) in plasma before and after treatment were analyzed to evaluate their clinical significance. Results: Cox regression analysis demonstrated that higher sPD-L1 levels before treatment significantly predicted unfavorable progression-free survival (PFS; HR 15.4, 95% CI 1.10–86.7, P = 0.009) and overall survival (OS; HR 11.4, 95% CI 1.19–52.3, P = 0.007) in NSCLC patients treated with ICI monotherapy (n = 122) but not in those treated with ICIs combined with chemotherapy (n = 67: P = 0.729 and P = 0.155, respectively). In addition, higher sPD-1 levels after treatment were significantly associated with better OS (HR 0.24, 95% CI 0.06–0.91, P = 0.037) in patients treated with anti-PD-1 monotherapy, whereas higher sPD-L1 levels after treatment were significantly associated with worse PFS (HR 6.09, 95% CI 1.42–21.0, P = 0.008) and OS (HR 42.6, 95% CI 6.83–226, P < 0.001). The levels of sPD-L1 at baseline closely correlated with those of other soluble factors, such as sCD30, IL-2Ra, sTNF-R1, and sTNF-R2, which are known to be released from the cell surface by zinc-binding proteases ADAM10/17. Conclusions: These findings suggest the clinical significance of pretreatment sPD-L1 as well as posttreatment sPD-1 and sPD-L1 in NSCLC patients treated with ICI monotherapy. [ABSTRACT FROM AUTHOR]

Abnormal peripheral perfusion (PP) worsens the prognosis of patients with septic shock. Polymyxin B-direct hemoperfusion (PMX-DHP) increases blood pressure and reduces vasopressor doses. However, the modification of PP following administration of PMX-DHP in patients with vasopressor-dependent septic shock have not yet been elucidated. A retrospective exploratory observational study was conducted in patients with septic shock treated with PMX-DHP. Pulse-amplitude index (PAI), vasoactive inotropic score (VIS), and cumulative fluid balance data were extracted at PMX-DHP initiation (T0) and after 24 (T24) and 48 (T48) h. Changes in these data were analyzed in all patients and two subgroups (abnormal PP [PAI < 1] and normal PP [PAI ≥ 1]) based on the PAI at PMX-DHP initiation. Overall, 122 patients (abnormal PP group, n = 67; normal PP group, n = 55) were evaluated. Overall and in the abnormal PP group, PAI increased significantly at T24 and T48 compared with that at T0, with a significant decrease in VIS. Cumulative 24-h fluid balance after PMX-DHP initiation was significantly higher in the abnormal PP group. PMX-DHP may be an effective intervention to improve PP in patients with abnormal PP; however, caution should be exercised as fluid requirements may differ from that of patients with normal PP. [ABSTRACT FROM AUTHOR]

Land-walking vertebrates maintain a desirable posture by finely controlling muscles. It is unclear whether fish also finely control posture in the water. Here, we showed that larval zebrafish have fine posture control. When roll-tilted, fish recovered their upright posture using a reflex behavior, which was a slight body bend near the swim bladder. The vestibular-induced body bend produces a misalignment between gravity and buoyancy, generating a moment of force that recovers the upright posture. We identified the neural circuits for the reflex, including the vestibular nucleus (tangential nucleus) through reticulospinal neurons (neurons in the nucleus of the medial longitudinal fasciculus) to the spinal cord, and finally to the posterior hypaxial muscles, a special class of muscles near the swim bladder. These results suggest that fish maintain a dorsal-up posture by frequently performing the body bend reflex and demonstrate that the reticulospinal pathway plays a critical role in fine postural control.The postural control mechanism in fish is unclear. Here, authors show that larval zebrafish recover upright posture after roll tilts by a body bend that produces corrective rotational torque. They also reveal the associated neural circuits and muscles. [ABSTRACT FROM AUTHOR]

Spatio-temporal information about head orientation and movement is fundamental to the sense of balance and motion. Hair cells (HCs) in otolith organs of the vestibular system transduce linear acceleration, including head tilt and vibration. Here, we build a tiltable objective microscope in which an objective lens and specimen tilt together. With in vivo Ca2+ imaging of all utricular HCs and ganglion neurons during 360° static tilt and vibration in pitch and roll axes, we reveal the direction- and static/dynamic stimulus-selective topographic responses in larval zebrafish. We find that head vibration is preferentially received by striolar HCs, whereas static tilt is preferentially transduced by extrastriolar HCs. Spatially ordered direction preference in HCs is consistent with hair-bundle polarity and is preserved in ganglion neurons through topographic innervation. Together, these results demonstrate topographically organized selectivity for direction and dynamics of head orientation/movement in the vestibular periphery. Signals about head orientation and movement in the vestibular periphery are fundamental to the sense of balance and motion, but difficult to measure systematically during head motion. Here, the authors build a microscope that visualizes neural activity in hair cells and vestibular ganglion cells during 360° head tilt and vibration in zebrafish larvae, and reveal a topographic organization of direction- and static/dynamic stimulus-selective responses. [ABSTRACT FROM AUTHOR]

Voltage-sensing phosphatase (Vsp) is a unique membrane protein that translates membrane electrical activities into the changes of phosphoinositide profiles. Vsp orthologs from various species have been intensively investigated toward their biophysical properties, primarily using a heterologous expression system. In contrast, the physiological role of Vsp in native tissues remains largely unknown. Here we report that zebrafish Vsp (Dr-Vsp), encoded by tpte gene, is functionally expressed on the endomembranes of lysosome-rich enterocytes (LREs) that mediate dietary protein absorption via endocytosis in the zebrafish mid-intestine. Dr-Vsp-deficient LREs were remarkably defective in forming endosomal vacuoles after initial uptake of dextran and mCherry. Dr-Vsp-deficient zebrafish exhibited growth restriction and higher mortality during the critical period when zebrafish larvae rely primarily on exogenous feeding via intestinal absorption. Furthermore, our comparative study on marine invertebrate Ciona intestinalis Vsp (Ci-Vsp) revealed co-expression with endocytosis-associated genes in absorptive epithelial cells of the Ciona digestive tract, corresponding to zebrafish LREs. These findings signify a crucial role of Vsp in regulating endocytosis-dependent nutrient absorption in specialized enterocytes across animal species. The physiological role of Vsp in zebrafish is assessed, revealing Vsp expression in the mid-intestine for dietary protein absorption. A comparative study on marine invertebrate Ciona intestinalis suggests conservation of Vsp function in the GI tract. [ABSTRACT FROM AUTHOR]

We evaluated the early effects of pars plana vitrectomy (PPV) on corneal biomechanics by comparing corneal hysteresis (CH) after cataract surgery (phacoemulsification and aspiration with intraocular lens implantation; PEA + IOL) alone and PPV combined with cataract surgery. This study included 20 eyes (18 patients), who underwent cataract surgery alone (PEA + IOL group), and 28 eyes (27 patients) who underwent PPV combined with cataract surgery (PPV triple group). The CH was 11.1 ± 1.1, 10.4 ± 1.1, and 11.0 ± 1.0 mmHg in the PEA + IOL group and 11.0 ± 1.4, 9.8 ± 1.4, and 10.6 ± 1.6 mmHg in the PPV triple group, preoperatively, at 2 weeks, and 3 months after surgery, respectively. The CH was not significantly different after surgery in the PEA + IOL group, but decreased significantly in the PPV triple group 2 weeks following surgery (p < 0.01). Intraocular pressure (IOP) and central corneal thickness (CCT) did not change significantly after surgery in either group. Preoperatively, there was a positive correlation between CH and CCT in the PPV triple group, but the correlation disappeared postoperatively. In PPV combined with cataract surgery, CH temporarily decreased postoperatively, independent of IOP and CCT. Removal of the vitreous may reduce the elasticity and rigidity of the entire eye. [ABSTRACT FROM AUTHOR]

Why are some electoral authoritarian regimes immune to democratization for decades while others not? This article explores the impact of executive selection systems on democratic transitions from electoral authoritarianism. We argue that under electoral authoritarian regimes, Parliament-based systems permit dictators to more effectively deter democratization compared to Presidential systems. This is because Parliament-based systems indirectly allow electoral manipulation to achieve a victory at the ballot box, such as through gerrymandering and malapportionment. Parliament-based systems also make it difficult for opposition parties to coordinate and incentivize autocrats and ruling elites to engage in power-sharing and thus institutionalize ruling parties. We test our hypothesis as well as the underlying mechanisms employing a dataset of 93 electoral authoritarian countries between 1946 and 2012. Cross-national statistical analyses with instrumental variables estimation provide supporting evidence for our theory. [ABSTRACT FROM AUTHOR]

Vascular injury associated with cannulation during extracorporeal membrane oxygenation (ECMO) induction is a rare but life-threatening complication. The presence of abnormal vascular anatomy increases the risk of vascular injury and should be recognized before cannulation. We report the case of a patient with coronavirus disease (COVID-19) who was expected to undergo ECMO. By performing computed tomography (CT), we identified the absence of right superior vena cava (RSVC) with a persistent left superior vena cava (PLSVC) that could have caused serious complications associated with ECMO cannulation. PLSVC is observed in less than 0.5% of the general population; however, the combination of PLSVC and an absent RSVC in visceroatrial situs solitus is extremely rare. Attempting cannulation for Veno-venous (VV)-ECMO from the right (or left) internal jugular vein to the right atrium may cause serious complications. Cannulation may fail or lead to complications even in patients with inferior vena cava malformations. Although these vascular abnormalities are rare, it is possible to avoid iatrogenic vascular injury by identifying their presence in advance. Since anatomical variations in the vessels from the deep chest and abdominal cavity cannot be visualized using chest radiography and ultrasonography, we recommend CT, if possible, for patients with severe respiratory failure, including those with COVID-19, who may be considered for VV-ECMO induction. [ABSTRACT FROM AUTHOR]

Developmental maturation occurs in slow swimming behavior in larval zebrafish; older larvae acquire the ability to perform slow swimming while keeping their head stable in the yaw dimension. A class of long-distance descending commissural excitatory V0v neurons, called MCoD neurons, are known to develop in a later phase of neurogenesis, and participate in slow swimming in older larvae. We hypothesized that these MCoD neurons play a role in coordinating the activities of trunk muscles in the diagonal dimension (e.g., the rostral left and the caudal right) to produce the S-shaped swimming form that contributes to the stability of the head. Here, we show that MCoD neurons do indeed play this role. In larvae in which MCoD neurons were laser-ablated, the swimming body form often adopted a one-sided (C-shaped) bend with reduced appearance of the normal S-shaped bend. With this change in swimming form, the MCoD-ablated larvae exhibited a greater degree of head yaw displacement during slow swimming. In mice, the long-distance descending commissural V0v neurons have been implicated in diagonal interlimb coordination during walking. Together with this, our study suggests that the long-distance descending commissural V0v neurons form an evolutionarily conserved pathway in the spinal locomotor circuits that coordinates the movements of the diagonal body/limb muscles. [ABSTRACT FROM AUTHOR]

Transient coaxial helicity injection (CHI) is a promising candidate for solenoid-free plasma current start-up in a low-aspect-ratio tokamak in support of developing fully non-inductive scenarios. The aim of the transient CHI research on QUEST is to develop a reactor-relevant CHI design. On QUEST, a CHI discharge is initiated by driving current along magnetic field lines that connect an electrically insulated electrode plate (which is referred to as a bias electrode) to a vessel component at the bottom region of the spherical tokamak. In the first application of CHI on QUEST, the electrically insulated electrode plate was biased with respect to the outer vessel in a configuration referred to as low-field-side (LFS) injection. To maintain a narrow injector flux footprint width throughout the discharge, QUEST is now developing a high-field-side (HFS) injection configuration, in which the electrically insulated electrode plate is biased with respect to the inner vessel components. Through the implementation of a CHI-dedicated gas injection system, studies in the HFS injection configuration have now demonstrated good magnetic flux evolution into the vacuum vessel. Toroidal currents up to 43 kA have been achieved, and the generated current has increased in proportion to the magnetic flux connecting the electrodes. These results which show agreement with the CHI-scaling suggest that much higher levels of toroidal current can be generated on QUEST in an optimized CHI system in which the magnetic flux connecting the CHI electrodes is further increased. [ABSTRACT FROM AUTHOR]

The lamprey represents the oldest group of living vertebrates and has been a key organism in various research fields such as evolutionary developmental biology and neuroscience. However, no knock-in technique for this animal has been established yet, preventing application of advanced genetic techniques. Here, we report efficient generation of F0 knock-in lampreys by CRISPR-Cas9-mediated genome editing. A donor plasmid containing a heat-shock promoter was co-injected with a short guide RNA (sgRNA) for genome digestion, a sgRNA for donor plasmid digestion, and Cas9 mRNA. Targeting different genetic loci, we succeeded in generating knock-in lampreys expressing photoconvertible protein Dendra2 as well as those expressing EGFP. With its simplicity, design flexibility, and high efficiency, we propose that the present method has great versatility for various experimental uses in lamprey research and that it can also be applied to other "non-model" organisms. [ABSTRACT FROM AUTHOR]

Peripartum cardiomyopathy (PPCM) is a life-threatening heart failure occurring in the peripartum period. Although mal-angiogenesis, induced by the 16-kDa N-terminal prolactin fragment (16 K PRL), is involved in the pathogenesis, the effect of full-length prolactin (23 K PRL) is poorly understood. We transfected neonate rat cardiomyocytes with plasmids containing 23 K PRL or 16 K PRL in vitro and found that 23 K PRL, but not 16 K PRL, upregulated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling, and hypoxia promoted this effect. During the perinatal period, cardiomyocyte-specific PERK homogenous knockout (CM-KO) mice showed PPCM phenotypes after consecutive deliveries. Downregulation of PERK or JAK/STAT signaling and upregulation of apoptosis were observed in CM-KO mouse hearts. Moreover, in bromocriptine-treated CM-KO mice, cardiac function did not improve and cardiomyocyte apoptosis was not suppressed during the peripartum period. These results demonstrate that interaction between 23 K PRL and PERK signaling is cardioprotective during the peripartum term. [ABSTRACT FROM AUTHOR]

Benzalkonium chloride (BAC) is used as a preservative in eyedrops but induces subconjunctival fibrosis that can result in failure of glaucoma surgery. Tenon's capsule fibroblasts in subconjunctival tissue interact with the corneal epithelium through tear fluid. With the use of a coculture system, we have now investigated the effect of human corneal epithelial (HCE) cells on myofibroblastic transdifferentiation of human Tenon fibroblasts (HTFs) induced by BAC (5 × 10−6%). Immunofluorescence and immunoblot analyses revealed that the BAC-induced expression of α smooth muscle actin (αSMA) in HTFs was suppressed by coculture of these cells with HCE cells (p < 0.01). The concentration of interleukin-10 (IL-10) in culture supernatants of BAC-treated HTFs was increased by coculture with HCE cells (17.26-fold, vs. coculure, p < 0.001). Immunofluorescence and immunoblot analyses also showed that exogenous IL-10 (300 pg/ml) suppressed the BAC-induced expression of αSMA by 43.65% (p < 0.05) as well as the nuclear translocation of myocardin-related transcription factor-A (MRTF-A) by 39.32% (p < 0.01) in HTFs cultured alone. Our findings suggest that corneal epithelial cells may protect against subconjunctival fibrosis by maintaining IL-10 levels and preventing the MRTF-A-dependent transdifferentiation of HTFs into myofibroblasts. [ABSTRACT FROM AUTHOR]

Septic shock is characterized by dysregulated vascular permeability. We hypothesized that the vascular permeability of endothelial cells (ECs) would be regulated by serotonin via serotonin-Rho-associated kinase (ROCK) signaling. We aimed to determine the impact of 5-hydroxyindoleacetic acid (5-HIAA) on septic shock as a novel biomarker. Plasma 5-HIAA levels and disease severity indices were obtained from 47 patients with sepsis. The association between 5-HIAA levels and severity indices was analyzed. Permeability upon serotonin stimulation was determined using human pulmonary microvascular ECs. 5-HIAA were significantly higher in septic shock patients than in patients without shock or healthy controls (p = 0.004). These elevated levels were correlated with severity indexes (SOFA score [p < 0.001], APACHE II [p < 0.001], and PaO2:FiO2 [p = 0.02]), and longitudinally associated with worse clinical outcomes (mechanical ventilation duration [p = 0.009] and ICU duration [p = 0.01]). In the experiment, serotonin increased the permeability of ECs, which was inhibited by the ROCK inhibitor (p < 0.001). Serotonin increases vascular permeability of ECs via ROCK signaling. This suggests a novel mechanism by which serotonin disrupts endothelial barriers via ROCK signaling and causes the pathogenesis of septic shock with a vascular leak. Serotonin serves as a novel biomarker of vascular permeability. [ABSTRACT FROM AUTHOR]

Epithelial–mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells plays a key role in proliferative retinal diseases such as age-related macular degeneration by contributing to subretinal fibrosis. To investigate the potential role of retinoic acid receptor-α (RAR-α) signaling in this process, we have now examined the effects of the RAR-α agonist Am580 on EMT induced by transforming growth factor-β2 (TGF-β2) in primary mouse RPE cells cultured in a three-dimensional type I collagen gel as well as on subretinal fibrosis in a mouse model. We found that Am580 inhibited TGF-β2-induced collagen gel contraction mediated by RPE cells. It also attenuated the TGF-β2-induced expression of the mesenchymal markers α-smooth muscle actin, fibronectin, and collagen type I; production of pro-matrix metalloproteinase 2 and interleukin-6; expression of the focal adhesion protein paxillin; and phosphorylation of SMAD2 in the cultured RPE cells. Finally, immunofluorescence analysis showed that Am580 suppressed both the TGF-β2-induced translocation of myocardin-related transcription factor-A (MRTF-A) from the cytoplasm to the nucleus of cultured RPE cells as well as subretinal fibrosis triggered by laser-induced photocoagulation in a mouse model. Our observations thus suggest that RAR-α signaling inhibits EMT in RPE cells and might attenuate the development of fibrosis associated with proliferative retinal diseases. [ABSTRACT FROM AUTHOR]

Purpose: Venous thromboembolism (VTE) is a major complication after abdominal surgery; however, the best strategy for preventing VTE after surgery is not yet established. We performed this study to investigate the incidence of perioperative VTE and evaluate the efficacy of a VTE preventive strategy for patients undergoing surgery for colorectal cancer (CRC). Methods: The subjects of this retrospective analysis were 228 patients who underwent curative surgical resection for CRC between 2012 and 2016. The patients were treated with thromboprophylaxis including enoxaparin. We assessed the perioperative VTE occurrence rate and investigated the risk factors for postoperative VTE. Results: Among the 228 patients, 77 had a preoperative D-dimer level of > 1.0 μg/mL and 12 had deep vein thrombosis (DVT) diagnosed by ultrasonography preoperatively. Of the remaining 216 patients, short-term VTE (< 30 days) developed in two patients (0.9%) and long-term VTE (30 days–3 years) developed in seven (3.2%). The mortality rate of patients with VTE was 0%. The univariate analysis indicated that pulmonary disease was the risk factor for short-term VTE, whereas obesity, hyperlipidemia, and a preoperative history of pulmonary embolism were the risk factors for long-term VTE (p < 0.05). Conclusion: The findings of this analysis show that our preventive protocol including enoxaparin is an effective strategy for preventing postoperative VTE. [ABSTRACT FROM AUTHOR]

Background: We clarified the safety and efficacy of preoperative chemoradiotherapy for locally advanced rectal cancer using a multidrug regimen (S-1 + oxaliplatin + bevacizumab). Methods: This multicenter phase II trial involved 47 patients with locally advanced rectal cancer. All patients received S-1 orally (80 mg/m2/day on days 1–5, 8–12, 15–19, and 22–26) and infusions of oxaliplatin (50 mg/m2 on days 1, 8, 15, and 22) and bevacizumab (5 mg/kg on days 1 and 15). The total radiation dose was 40 Gy delivered in daily fractions of 2 Gy via the four-field technique. The primary endpoint was the pathological complete response rate. The secondary endpoints were safety (incidence of adverse events) and clinical response, relapse-free survival, overall survival, local recurrence, R0 resection, downstaging, and treatment completion rates. Results: All 47 patients received chemoradiotherapy, and 44 patients underwent curative resection. Two patients refused surgery and selected a watch-and-wait strategy. The pathological complete response rate was 18.2% in patients who underwent curative resection. The clinical response rate was 91.3% in 46 patients. Concerning hematotoxicity, there was one grade 4 adverse event (2.1%) and seven grade 3 events (14.9%). Diarrhea was the most frequent non-hematotoxic event, and the grade 3 event rate was 25.5%. Conclusions: Although preoperative chemoradiotherapy for patients with locally advanced rectal cancer using the S-1 + oxaliplatin + bevacizumab regimen did not achieve the expected pathological complete response rate, this regimen led to an improved clinical response rate. [ABSTRACT FROM AUTHOR]

Introduction: The pre-operative three-dimensional (3D) imaging technique has resulted in a better surgical outcome for patients and has been used as an education and diagnostic tool. However, there are no reports concerning the usefulness of the 3D imaging technique in laparoscopic transabdominal pre-peritoneal repair (TAPP) so the aim of this study was to investigate the usefulness of the 3D imaging technique in laparoscopic TAPP as an educational tool for medical students.Patients and Methods: Six (6) patients who underwent laparoscopic TAPP for inguinal hernia were enrolled in this study. 3D reconstruction was performed from pre-operative computed tomography (CT) and the usefulness of pre-operative 3D simulation compared with intra-operative laparoscopic imaging was validated. Moreover, thirty (30) medical students at the university completed a multiple-choice questionnaire (MCQ) to determine the level of their satisfaction and understanding of anatomy resulting from the study.Result: The local anatomy of the patients was identified as the same during the operation as the pre-operative 3D simulation. The results of the MCQ showed that most of the medical students were extremely (23%) or very (67%) satisfied with the effect of pre-operative 3D simulation on the quality of the surgery. Moreover, most students could understand the surgery anatomy by the 3D simulation extremely well (40%) or very well (47%) and agreed on the usefulness of this procedure for learning anatomy.Conclusions: Pre-operative 3D simulation increases the understanding of detailed anatomy and virtual three-dimensional image analysis in laparoscopic TAPP is useful as an educational tool for medical students. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate gut inflammation and permeability in rats after duodenal-jejunal bypass (DJB) and in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Methods: Twelve male 16-week-old obese diabetic rats were divided into three groups: the DJB group, the sham group, and the group injected daily with a GLP-1 receptor agonist (liraglutide). Gut inflammation and the expression of tight junction protein (claudin-1) were analyzed in the three groups at 8 weeks after surgery. Results: The DJB group showed significantly lower levels of gut inflammatory cytokines than the liraglutide group. Claudin-1 showed stronger intensity on immunofluorescent staining in the DJB group than that in the liraglutide group. Conclusions: In summary, DJB surgery might maintain gut permeability via suppression of gut inflammation. [ABSTRACT FROM AUTHOR]

Ethnic inequality has been argued to have numerous pernicious effects. Among other things, scholars have argued that it breeds political violence, destabilizes democracy, and impedes economic development. While the arguments developed by these literatures implicitly assume that ethnic inequality increases the degree to which individuals identify with their ethnicity, this assumption has yet to be tested empirically at the individual-level. This paper argues and empirically demonstrates that between-ethnic group inequality does strengthen ethnic identities. However, we also find that the magnitude of its effect weakens as inequality within ethnic groups increases. That is, individuals identify most strongly with their ethnic identity when ethnicity is reinforced by economic inequality. Using the Afrobarometer, we provide the first cross-national empirical test of the effect of ethnic inequality on the strength of ethnic identities at the individual-level. Our dataset covers 21 sub-Saharan African countries and 85 ethnic groups. Results strongly support our hypothesis. [ABSTRACT FROM AUTHOR]

The aim of this study was to clarify the association between circulating pregnancy-associated, placenta-specific microRNAs (miRNAs) in maternal plasma and placental abruption. All samples were obtained after receiving written informed consent, and the study protocol was approved by the institutional review board. Maternal blood samples (7 mL) were obtained at 25 to 40 weeks of gestation from 15 cases of placental abruption (placental abruption group) and from 24 cases of uncomplicated pregnancies (uncomplicated pregnancy group). The plasma concentrations of pregnancy-associated, placenta-specific miRNAs (miR-515-3p, -517a, -517c, and -518b) were measured by quantitative real-time reverse transcription-polymerase chain reaction. There were no significant differences in clinical characteristics between the 2 groups. The median concentration of plasma cell-free miR-517c in the placental abruption group was 21 672.2 copies/mL, whereas that in the uncomplicated pregnancy group was 13 452.0 copies/mL (Mann-Whitney U test, P = .047). Receiver operating characteristic curve analysis revealed that plasma cell-free miR-517c levels discriminated placental abruption from uncomplicated pregnancy with an area under the curve of 0.692. When a cutoff negative/positive value of 15 669.6 copies/mL was selected, the sensitivity and specificity were 73.3% and 62.5%, respectively. In addition, the positive and negative predictive values were 55.0% and 78.9%, respectively. Plasma cell-free miR-517a and miR-517c levels in the large abruption (degree of abruption ≥50% of placenta) group were significantly higher than in the small abruption (<50%) group (P = .03 for both miRNAs). In conclusion, the circulating level of cell-free miR-517c in maternal plasma was increased as a consequence of placental abruption and may be a potential biomedical marker for placental abruption. [ABSTRACT FROM AUTHOR]

This study investigated the composition of the gut microbiota in rats after duodenal-jejunal bypass (DJB) in comparison to that in rats injected with a glucagon-like peptide-1 (GLP-1) receptor analog. Six male 16-week-old OLETF rats were divided into three groups: a DJB group, a sham operation group, and a daily injection with a GLP-1 receptor agonist (liraglutide) group. The gut microbiota of the three groups was analyzed at postoperative week 8 using the PCR-clone library method targeting the 16S ribosomal RNA gene. The DJB group showed a decrease in Bacteroidia in comparison to the other two groups (DJB, 3.9 %/2.8 %; sham, 10.8 %/11.6 %; liraglutide, 33.2 %/14.1 %). In addition, DJB markedly increased the ratio of Gammaproteobacteria (DJB, 10.8 %/13.7 %; sham, 0.2 %/1.2 %; liraglutide, 0 %/0.1 %). DJB changes the composition of gut microbiota; these changes might be the factors that contribute to the effects of DJB. [ABSTRACT FROM AUTHOR]

Purpose: Sevoflurane is known to prolong the QT interval. This study aimed to determine the effect of the interaction between intravenous anesthetics and sevoflurane on the QT interval. Methods: The study included 48 patients who underwent lumbar spine surgery. Patients received 3 μg/kg fentanyl and were then randomly allocated to either Group T, in which they received 5 mg/kg thiamylal, or Group P, in which they received 1.5 mg/kg propofol, at 2 min after administration of fentanyl injection for anesthetic induction. Vecuronium (1.5 mg/kg) and sevoflurane (3 % inhaled concentration) were administered immediately after loss of consciousness and tracheal intubation was performed 3 min after vecuronium injection. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and the heart rate-corrected QT (QTc) interval on a 12-lead electrocardiogram were recorded immediately before fentanyl administration (T1), 2 min after fentanyl injection (T2), immediately before intubation (T3), and 2 min after intubation (T4). Results: There were no significant differences between the two groups in baseline patient characteristics. BIS and MAP significantly decreased after anesthesia induction in both groups. At T3, MAP in Group T was higher than in Group P, while HR had reduced in both groups. The QTc interval was prolonged after anesthesia induction in Group T, but did not change at any time point in Group P. The QTc interval after anesthesia induction in Group T was longer than in Group P. Conclusion: We concluded that an injection of propofol could counteract QTc interval prolongation associated with sevoflurane anesthesia induction. [ABSTRACT FROM AUTHOR]

This paper explores the conditions under which democratic elections encourage citizens to identify with ethnicity. We argue that there are two mechanisms through which elections strengthen ethnic identification. First, the stronger ethnic parties are, the more intensive, ethnically exclusive political campaigns they carry out as an election approaches, resulting in strengthening citizens' ethnic identity. Second, ethnic party mobilization drives members of other ethnic groups to develop stronger identity to their own ethnicity because such mobilization poses a serious political threat to the out-group members. Data analysis of approximately 18,000 respondents in five waves of the New Baltic Barometer supports the hypotheses. A case study of Latvia follows to illustrate that ethnic party mobilization for elections creates ethnic cleavages among the public. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death protein 1 (PD-1) and its ligand PD-L1 downregulate T cell activation and are related to immune tolerance. The aim of this study was to clarify the significance of PD-1 and PD-L1 expression and to analyze the relationships among PD-1, PD-L1, and Foxp3 expression in gastric cancer. Methods: A total of 105 patients who underwent curative gastrectomy for stage II/III gastric cancer were included in this study. PD-1, PD-L1, and Foxp3 expression were examined by immunohistochemistry and related to prognostic factors by univariate and multivariate analyses. Results: PD-1 expression was correlated with both PD-L1 and Foxp3 expression. Disease-free survival (DFS) was significantly poorer in PD-1-positive patients than in PD-1-negative patients (3-year DFS, 36.1 % vs. 64.7 %, respectively; p < 0.05). Overall survival also tended to be poorer in PD-L1-positive patients than in PD-L1-negative patients. Univariate analysis identified sex, T factor, lymphatic invasion, and PD-1 positivity as significant predictors of poor DFS. Multivariate analysis confirmed male sex, lymphatic invasion, and positive PD-1 expression as independent prognostic indicators. Conclusions: PD-1 expression is associated with a poor prognosis and is correlated with PD-L1 and Foxp3 expression in patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to clarify the association between placenta previa and circulating levels of cell-free pregnancy-associated placenta-specific microRNAs (miRNAs) in maternal plasma. Method: Twenty singleton pregnancies with placenta previa (placenta previa group) and 26 uncomplicated pregnancies (control group) were recruited. Blood sampling was performed at 32 weeks of gestation, and cesarean delivery in all cases of placenta previa was performed at a mean gestational age of 37 weeks. The maternal plasma concentrations of cell-free pregnancy-associated placenta-specific miRNAs (miR-517a and miR-518b) were measured by absolute quantitative real-time reverse transcription-polymerase chain reaction. Results: Plasma concentrations of cell-free miR-517a were significantly higher in the placenta previa group than that in the control group (P = .011), while the plasma concentration of cell-free miR-518b was significantly lower in the placenta previa group than that in the control group (P = .004). Plasma concentrations of cell-free miR-517a in placenta previa were significantly higher in placenta previa with alert bleeding later group than those in placenta previa without alert bleeding group or control group (P = .030 or .047, respectively) and correlated with the volume of hemorrhage at delivery (R and P value: .512 and .025). Conclusion: Plasma concentrations of cell-free miR-517a and miR-518b at 32 weeks of gestation were altered in pregnant women with placenta previa, and the circulating level of cell-free miR-517a in placenta previa may be a predictive marker for the risks of alert bleeding later and massive hemorrhage at delivery. [ABSTRACT FROM AUTHOR]

Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The original article can be found online at https://doi.org/10.1007/s12116-022-09350-3. [Extracted from the article]

Background: Peripheral sensory neurotoxicity is a frequent adverse effect of oxaliplatin therapy. Calcium and magnesium (Ca/Mg) infusions are frequently used as preventatives, but a recent phase III trial failed to show that they prevent neurotoxicity. We therefore conducted a multicenter randomized phase III trial to compare fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) with and without Goshajinkigan (GJG), a traditional Japanese herbal medicine (Kampo), to determine GJG's potential for reducing peripheral neuropathy in patients with colorectal cancer. Methods: Patients with colon cancer who were undergoing adjuvant therapy with infusional mFOLFOX6 were randomly assigned to GJG (7.5 mg three times daily) or placebo in a double-blind manner. The primary endpoint was the time to grade 2 or greater neuropathy, which was determined at any point during or after oxaliplatin-based therapy using version 3 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Findings: An interim analysis was performed when 142 of the planned 310 patients had been enrolled and the safety assessment committee recommended that the study be discontinued. One hundred eighty-two patients were evaluable for response. They included 89 patients in the GJG group and 93 patients in the placebo group. The incidence of grade 2 or greater neurotoxicity was 50.6 % in the GJG group and 31.2 % in the placebo group. A Cox proportional hazards analysis indicated that the use of GJG was significantly associated with the incidence of neuropathy (hazard ratio, 1.908; p = 0.007). Conclusion: Goshajinkigan did not prevent oxaliplatin-associated peripheral neuropathy in this clinical trial. The clinical study was therefore terminated. [ABSTRACT FROM AUTHOR]

The type II bacterial CRISPR/Cas9 system is rapidly becoming popular for genome-engineering due to its simplicity, flexibility, and high efficiency. Recently, targeted knock-in of a long DNA fragment via homology-independent DNA repair has been achieved in zebrafish using CRISPR/Cas9 system. This raised the possibility that knock-in transgenic zebrafish could be efficiently generated using CRISPR/Cas9. However, how widely this method can be applied for the targeting integration of foreign genes into endogenous genomic loci is unclear. Here, we report efficient generation of knock-in transgenic zebrafish that have cell-type specific Gal4 or reporter gene expression. A donor plasmid containing a heat-shock promoter was co-injected with a short guideRNA(snRNA) targeted for genome digestion, a sgRNA targeted for donor plasmid digestion, and Cas9 mRNA. We have succeeded in establishing stable knock-in transgenic fish with several different constructs for 4 genetic loci at a frequency being exceeding 25%. Due to its simplicity, design flexibility, and high efficiency, we propose that CRISPR/Cas9-mediated knock-in will become a standard method for the generation transgenic zebrafish. [ABSTRACT FROM AUTHOR]

Background: Although the internal hernias have been a huge topic in the field of bariatric surgery, there were a few reports in gastric cancer. The purpose of this study was to analyze the incidence, clinical features, and prevention of internal hernia after gastrectomy for gastric cancer. Methods: Twelve patients who underwent surgical treatment for internal hernia in our hospital after gastrectomy were analyzed. Features, including incidence, symptoms, and signs, were investigated in detail. Results: The operative procedures for preceding gastrectomies were open distal gastrectomy in three patients, open total gastrectomy in three patients, laparoscopic-assisted distal gastrectomy in two patients, and laparoscopic total gastrectomy in four patients. The most frequent sites of internal hernias were jejunojejunostomy mesenteric defects (five patients) and Petersen's defect (five patients), mesenterium of transverse colon (one patient), and esophagus hiatus (one patient). There was no significant difference between open and laparoscopic preceding gastrectomies. After closure of the mesenteric defect was introduced, no further internal hernias occurred. On CT examination, the whirl sign was present in ten patients on 3D images. Conclusions: The present data suggest the importance of early recognition and treatment of internal hernia, as well as its prevention by closure of mesenteric defects. [ABSTRACT FROM AUTHOR]

The relationship between oncogenic human papillomavirus (HPV) infection and later cytological findings in the uterine cervix is unknown in women who were negative for intraepithelial lesion and malignancy (NILM) or atypical squamous cells of undetermined significance (ASC-US). This was investigated in this study in a Japanese population to determine the clinical utility of oncogenic (HPV) genotyping. The relative risk of progressive cytological findings 2 years after identification of oncogenic HPV infection was higher than in cases of non-oncogenic HPV infection (relative risk 3.827; 95% confidence interval (CI): 1.282-11.422), as well as in cases of negative HPV infection (relative risk 2.124; 95% CI: 1.451-3.110). Moreover, the relative risk of progression of cytological findings 2 years later in cases of HPV-16 infection was higher than in cases of HPV-52 infection (relative risk 2.094; 95% CI: 1.005-3.935). Therefore, the initial HPV-DNA genotype may be a potential predictive marker of later progression of cytological findings in the uterine cervix in cases of NILM or ASC-US. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate association between copy number variation of the defensin beta 4 gene (DEFB4) and susceptibility to cervical cancer in a population at high risk of persistent oncogenic human papillomavirus (HPV) infection. The study subjects comprised 204 women with cervical cancer, a population having a high risk of persistent oncogenic HPV infection (cervical cancer group), and 200 healthy women from the general population (control group). Copy number variation of DEFB4 in each test sample was determined by relative quantitation using the comparative CT (ΔΔCT) method. Differences between the two groups were evaluated. The median DEFB4 copy number in the cervical cancer group was four and in the control group was five (P=2.77e-4, t-test). The odds ratio of cervical cancer in individuals with four DEFB4 copies or less was higher (odds ratio 2.02; 95% confidence interval odds ratio 1.36-3.02), compared with that in individuals with five or more copies (odds ratio 0.49; 95% confidence interval odds ratio 0.33-0.74). We found copy number variation of DEFB4 was a host genetic factor conferring susceptibility to cervical cancer. A lower DEFB4 copy number was associated with susceptibility to cervical cancer. [ABSTRACT FROM AUTHOR]

In vertebrate development, the body plan is determined by primordial morphogen gradients that suffuse the embryo. Retinoic acid (RA) is an important morphogen involved in patterning the anterior-posterior axis of structures, including the hindbrain and paraxial mesoderm. RA diffuses over long distances, and its activity is spatially restricted by synthesizing and degrading enzymes. However, gradients of endogenous morphogens in live embryos have not been directly observed; indeed, their existence, distribution and requirement for correct patterning remain controversial. Here we report a family of genetically encoded indicators for RA that we have termed GEPRAs (genetically encoded probes for RA). Using the principle of fluorescence resonance energy transfer we engineered the ligand-binding domains of RA receptors to incorporate cyan-emitting and yellow-emitting fluorescent proteins as fluorescence resonance energy transfer donor and acceptor, respectively, for the reliable detection of ambient free RA. We created three GEPRAs with different affinities for RA, enabling the quantitative measurement of physiological RA concentrations. Live imaging of zebrafish embryos at the gastrula and somitogenesis stages revealed a linear concentration gradient of endogenous RA in a two-tailed source-sink arrangement across the embryo. Modelling of the observed linear RA gradient suggests that the rate of RA diffusion exceeds the spatiotemporal dynamics of embryogenesis, resulting in stability to perturbation. Furthermore, we used GEPRAs in combination with genetic and pharmacological perturbations to resolve competing hypotheses on the structure of the RA gradient during hindbrain formation and somitogenesis. Live imaging of endogenous concentration gradients across embryonic development will allow the precise assignment of molecular mechanisms to developmental dynamics and will accelerate the application of approaches based on morphogen gradients to tissue engineering and regenerative medicine. [ABSTRACT FROM AUTHOR]

Purpose: Patients undergoing extensive cervical spine surgery (ECSS) occasionally require emergency reintubation due to postoperative airway complications. To avoid it, an endotracheal tube is retained in patients maintained under sedation overnight. This study was conducted to determine whether dexmedetomidine would be superior in sedative effects to propofol for postoperative sedation after ECSS. Methods: We studied 32 consecutive patients undergoing ECSS who required prophylactic intubation postoperatively under sedation overnight. The patients were randomly divided into two groups. Group D ( n = 16) received dexmedetomidine 0.1 μg/kg/min for 10 min as a loading dose, followed by a continuous infusion at 0.4 μg/kg/h. Group P ( n = 16) received propofol 0.1 mg/kg/min for 10 min as a loading dose, followed by a continuous infusion at 1 mg/kg/h. All patients received analgesia with buprenorphine. Ramsay sedation scale, extremity movement, and pain intensity were recorded every 2 h. Dexmedetomidine and propofol dosages were adjusted to maintain a desired sedation level. Nursing staff adjusted dopamine to maintain systolic blood pressure >100 mmHg and administered atropine when the heart rate was <50 bpm. Results: The proportions of adequate sedation level, movement, and pain status were similar between groups. In group D, heart rates were lower, frequency of atropine use was greater, and dopamine dose was higher than in group P. Conclusion: Both sedatives are efficacious after ECSS; however, dexmedetomidine decreased heart rate and required higher dose of dopamine. [ABSTRACT FROM AUTHOR]

Purpose: The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. Methods: Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. Results: Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT ( P < 0.05). The number and height of jejuna villi, injury score, and apoptosis index in the CPT-11 group were improved significantly by DKT ( P < 0.05). Conclusions: DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but its main dose-limiting toxicity is sensory neuropathy. The OPTIMOX (stop and go) approach offers a reasonable strategy, but the preventive agent is not established. It is reported that the Kampo medicine, Goshajinkigan (GJG), has recently been considered an effective agent for the neuropathy of taxanes and for vibration sensation in patients with diabetic neuropathy. The aim of this study was to clarify the efficacy of GJG for peripheral neuropathy associated with oxaliplatin therapy. Patients and method: From 2007, 45 patients treated with modified FOLFOX6 for non-resectable or recurrent colorectal cancer participated in the study. Twenty-two patients (GJG group) received oral administration of 7.5 g/day of GJG every day during mFOLFOX6 therapy and 23 patients (control group) did not receive GJG. Neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm). Results: The median number of cycles per patient in the GJG group was 13 (range 4-32), and in the control group was 12 (range 4-28). The cumulative dose of oxaliplatin was 1105 mg/m (GJG group) and 1120 mg/m (control group). The incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group ( p < 0.01, log-rank test). The incidence of grade 3 peripheral neuropathy after 10 courses was 0% in the GJG group and 12% in the control group, and after 20 courses was 33% in the GJG group and 75% in the control group. The percentage of grade 2 and 3 peripheral neuropathy in the GJG group was lower than that in the control group. There were no differences in adverse effects between the two groups except for peripheral neuropathy and influence on tumor response. Conclusion: The Kampo medicine, Goshajinkigan, is useful in preventing neuropathy in non-resectable or recurrent colorectal cancer patients treated with a FOLFOX regimen. [ABSTRACT FROM AUTHOR]

As the first step in prenatal diagnosis of X-linked genetic disorders, chorionic villus sampling (CVS) for fetal sex determination is generally performed at 11-13 weeks of gestation. However, as the procedure-related miscarriage rate of CVS is 0.5-1.0%, non-invasive methods such as PCR of cell-free fetal DNA (cff-DNA) in maternal plasma are preferable. Here, we determined fetal sex at 9-12 weeks of gestation using PCR of cff-DNA in three pregnant carriers of Duchenne muscular dystrophy. The fetal sex was accurately determined in all three cases, as confirmed by ultrasound and amniocentesis at 16 weeks (for the two female fetuses) and CVS at 12 weeks (for the one male fetus). This procedure could avoid unnecessary CVS in female fetuses. [ABSTRACT FROM AUTHOR]

Background: Prolonged heart rate-corrected QT (QTc) interval is frequently observed in subarachnoid hemorrhage (SAH). This study was conducted to determine the relationship between QTc interval and neurological outcome during the acute posthemorrhagic period after aneurysmal SAH. Methods: We studied 71 patients undergoing surgery who were admitted within 24 h after the onset of aneurysmal SAH. Standard 12-lead electrocardiography was performed on admission (T1) and at 1 and 7 days after operation (T2 and T3). QT intervals were corrected by heart rate according to the Fridericia formula. The Glasgow Coma Scale (GCS) score was calculated over the period T1-T3. Neurological outcome was assessed using the Glasgow Outcome Scale at hospital discharge. Results: Among the 71 patients, 31 had an unfavorable neurological outcome. Although QTc interval prolongation improved in patients with a good outcome, QTc interval prolongation continued in patients with an unfavorable outcome. The areas under the receiver-operator characteristic curves showed that the QTc and GCS score at T3, and the Hunt and Hess grade were significant predictors of an unfavorable neurological outcome. The threshold value, sensitivity, and specificity for the QTc at T3 were 448 ms, 73% [95% confidence interval (CI), 68-78], and 93% (95% CI, 90-96), respectively. Conclusion: This study confirms that QTc interval prolongation continues in the SAH patients with an unfavorable outcome but that QTc interval prolongation improves in patients with a good outcome, suggesting that a QTc interval of more than 448 ms at 7 days after operation is a predictor of neurological outcome after SAH. [ABSTRACT FROM AUTHOR]

The activation of Hedgehog signaling, which is critical to normal mammalian gastrointestinal development, is implicated in the development of various tumors, including colorectal cancer. In the pancreas, a precursor lesion overexpresses the Sonic hedgehog (Shh) when compared with normal tissue and cancer. The present study was designed to investigate Shh related protein expression in hyperplastic polyps and the adenoma-carcinoma sequence in the colon and rectum. Seventeen hyperplastic polyps, 24 adenomas of the colon, 69 adenocarcinomas (31 well-differentiated, 38 moderately-differentiated), and 30 normal colon samples were used in the study. We checked the expression of Shh, both patched (Ptch) and smoothened (Smo), by immunohistochemistry and compared the expression rate of each group. Almost all adenomas, 22 of 23 (96%), expressed Shh. In other groups, 4 of 17 hyperplastic polyps (24%), 7 of 31 well-differentiated adenocarcinomas (23%), 13 of 38 moderately-differentiated adenocarcinomas (34%) and none of the 30 normal samples expressed Shh. The rate of expression in Ptch and Smo gradually increased in accordance with tumor progression. This result indicates that Shh-related carcinogenesis and Shh expression may be a trigger for the adenoma-carcinoma sequence. This study suggests a potential therapeutic target of hedgehog blockade in carcinogenesis. [ABSTRACT FROM AUTHOR]

Kampo medicine "Dai-kenchu-to" (DKT) has been used for treatment of ileus. The aim of this study was to evaluate the role of DKT on the bacterial translocation (BT) model in rats. Rats were divided into the following four groups: group 1, receiving only water, and groups 2, 3, and 4, receiving 100, 300, and 1,000 mg/kg/day of DKT. Rats were sacrificed 6 days after the beginning of the fast, and then the mesenteric lymph node was cultured. Inflammatory cytokines, intestinal integrity, and apoptosis were assessed. Incidence of BT in groups 3 (33%) and 4 (16%) was lower than in group 1 (66%). Interferon-gamma expression in groups 2, 3, and 4 was significantly lower than in group 1. Villous height and number of villus in groups 2, 3, and 4 were significantly taller and greater than in group 1. Apoptotic index in groups 2, 3, and 4 was significantly lower than in group 1. This is the first evidence that DKT prevents BT by reducing inflammatory reaction and maintaining intestinal integrity. [ABSTRACT FROM AUTHOR]

Abstract  Kampo medicine “Dai-kenchu-to” (DKT) has been used for treatment of ileus. The aim of this study was to evaluate the role of DKT on the bacterial translocation (BT) model in rats. Rats were divided into the following four groups: group 1, receiving only water, and groups 2, 3, and 4, receiving 100, 300, and 1,000 mg/kg/day of DKT. Rats were sacrificed 6 days after the beginning of the fast, and then the mesenteric lymph node was cultured. Inflammatory cytokines, intestinal integrity, and apoptosis were assessed. Incidence of BT in groups 3 (33%) and 4 (16%) was lower than in group 1 (66%). Interferon-γ expression in groups 2, 3, and 4 was significantly lower than in group 1. Villous height and number of villus in groups 2, 3, and 4 were significantly taller and greater than in group 1. Apoptotic index in groups 2, 3, and 4 was significantly lower than in group 1. This is the first evidence that DKT prevents BT by reducing inflammatory reaction and maintaining intestinal integrity. [ABSTRACT FROM AUTHOR]

Animals move over a range of speeds by using rhythmic networks of neurons located in the spinal cord. Here we use electrophysiology and in vivo imaging in larval zebrafish (Danio rerio) to reveal a systematic relationship between the location of a spinal neuron and the minimal swimming frequency at which the neuron is active. Ventral motor neurons and excitatory interneurons are rhythmically active at the lowest swimming frequencies, with increasingly more dorsal excitatory neurons engaged as swimming frequency rises. Inhibitory interneurons follow the opposite pattern. These inverted patterns of recruitment are independent of cell soma size among interneurons, but may be partly explained by concomitant dorso-ventral gradients in input resistance. Laser ablations of ventral, but not dorsal, excitatory interneurons perturb slow movements, supporting a behavioural role for the topography. Our results reveal an unexpected pattern of organization within zebrafish spinal cord that underlies the production of movements of varying speeds. [ABSTRACT FROM AUTHOR]

The anti-anginal drug nicorandil has been demonstrated to protect the myocardium against ischemic injury in both experimental and clinical studies. Although nicorandil seems to protect the myocardium via activation of mitochondrial ATP-sensitive K+ (mitoKATP) channels, the mechanisms underlying its cardioprotection have remained elusive. We therefore examined whether nicorandil depolarizes the mitochondrial membrane and attenuates the mitochondrial Ca2+ overload. With the use of a Nipkow confocal system, the mitochondrial Ca2+ concentration ([Ca2+]m) and the mitochondrial membrane potential (ΔΨm) in rat ventricular myocytes were measured by loading cells with rhod-2 and JC-1 respectively. The number of cell hypercontractures resulting from mitochondrial Ca2+ overload was counted. Exposing cells to ouabain (1 mM) evoked mitochondrial Ca2+ overload and increased the intensity of rhod-2 fluorescence to 180±15% of baseline (p<0.001). Nicorandil (100 μM) significantly attenuated the ouabain-induced mitochondrial Ca2+ overload (129±4% of baseline; p<0.001 vs. ouabain). Nicorandil decreased the ΔΨm during application of ouabain, thereby reducing the intensity of JC-1 fluorescence to 89±2% of baseline (p<0.05). Exposure of myocytes to ouabain eventually resulted in cell hypercontracture (51±2%). This ouabain-induced cell hypercontracture was blunted by application of nicorandil (37±2%, p<0.05 vs. ouabain). Moreover, these effects of nicorandil were abolished by 5-hydroxydecanoate (500 μM), a putative mitoKATP channel blocker, and by glibenclamide (10 μM), a nonselective KATP channel blocker. Our results suggest that nicorandil attenuates the matrix Ca2+ overload with accompanying depolarization of the mitochondrial membrane. Such effect might potentially be attributed to the mechanism of cardioprotection afforded by nicorandil. [ABSTRACT FROM AUTHOR]

The object of the study was to model fixed-bearing knee prostheses (FBKs) and mobile-bearing knee prostheses (MBKs) during weight-bearing deep knee bends and to analyse and compare the kinematics of the two prosthesis types. To obtain quantitative data, an overall model of a leg was constructed, and this included a three-dimensional model of the tibiofemoral joint and simplified two-dimensional models of the ankle and patellofemoral joint. The simulated movement pattern of the tibiofemoral contact point in the FBK was analysed to show the posterior contact position on the tibia at full extension and anterior translation as the knee was flexed from 30 degrees to 90 degrees. The simulated maximum displacements of the medial and lateral contact positions of the FBK were 5.6 and 6.2 mm, respectively. These results were almost in agreement with experimental studies. Compared with the FBK, the movement pattern of the tibiofemoral contact point in the MBK for the anterior contact position on the tibia at full extension and posterior translation, with respect to the tibia as the knee was flexed, gave results closer to those of the normal knee. The simulated displacements of the medial and lateral contact positions of the MBK with respect to the tibia were 9.0 and 13.0 mm from full extension to 90 degrees flexion, respectively. The difference in the kinematic results between the FBK and the MBK could be accounted for by movement of the insert and the larger force of the posterior cruciate ligament on the MBK. [ABSTRACT FROM AUTHOR]

To examine the initial step of brown pigment gallstone formation, sterile human gallbladder bile samples were incubated with or without β-glucuronidase in vitro. Enhanced bilirubin deconjugation achieved by adding β-glucuronidase significantly accelerated the formation of a precipitate that contained bilirubin (28.2±3.8% of dry weight), cholesterol (14.3±5.2%), free fatty acids (12.0±1.3%), and glycoprotein (10.0±6.7%). Both the composition and scanning electron microscopic appearance of the precipitate were similar to these features in brown pigment gallstones. The cholesterol saturation index and nucleation time in the supernatant did not change with various incubation periods. The weight ratios of bilirubin to cholesterol in the precipitates correlated with those in bile ( r=0.76; P=0.017). Gel chromatography of the precipitate showed high molecular weight glycoprotein to be the major constituent. Bilirubin, cholesterol, fatty acids, and mucin were found to coprecipitate in accordance with bilirubin deconjugation, which process may play an important role in an early stage of the formation of brown pigment gallstones. [ABSTRACT FROM AUTHOR]

The upstream region of the isocitrate lyase gene (UPR-ICL, 1530bp) of an n-alkane-utilizable yeast, Candida tropicalis, induced gene expression in another yeast, Saccharomyces cerevisiae, when the yeasts were grown on acetate. Surprisingly, UPR-ICL displayed the same regulatory function in the bacterium Escherichia coli when grown on acetate. We determined the interesting nucleotide sequence of UPR-ICL. The deletion analysis of UPR-ICL in both cells revealed the presence of two distinct promoters: one was localized at-394 to-379 and regulated gene expression in S. cerevisiae; the other was tocated near the initiation codon and regulated gene expression in E. coli. The two promoter sequences were similar, but not identical to regulatory elements that have been previously reported in S. cerevisiae and E. coli, respectively. Accordingly, the possibility of novel regulatory mechanisms could not be excluded. This is an interesting example of the presence of distinct cis-acting regulatory elements responsible for the induction of gene expression in one gene by acetate in both S. cerevisiae and E. coli. Preservation of such promoters through evolution is also discussed. [ABSTRACT FROM AUTHOR]