Predictors of early withdrawal from follow-up visits after laparoscopic sleeve gastrectomy in a Japanese institution.

PURPOSE: Postoperative weight loss is related to postoperative adherence to follow-up after bariatric/metabolic surgery, but many patients stop attending follow-up visits early. The aim of this study was to clarify predictors of early withdrawal from follow-up after laparoscopic sleeve gastrectomy (LSG) in a Japanese institution. METHODS: One hundred and fifty-three patients who underwent LSG were retrospectively included in this study. Multivariate analysis was performed to evaluate independent predictors of withdrawal from follow-up visits within 12 months after LSG among significant or nearly significant factors in the univariate analyses. The discrimination power of significant factors was estimated using area under the receiver operating characteristic curve (AUC). RESULTS: Within 12 months after LSG, 25 of the 153 patients withdrew from follow-up visits. The multivariate analysis showed that age was the only significant predictor of withdrawal. The AUC for age was 0.685, and the cut-off value was < 40 years. The younger patients (< 40 years old) had a significantly higher rate of withdrawal compared with the older patients (≥ 40 years) (27.0% vs. 8.9%). CONCLUSION: Older Japanese patients (≥ 40 years old) may be better candidates for LSG. We consider it significant to continue to emphasize the importance of follow-up visits in younger patients after LSG.

Central regulation of body fluid homeostasis.

Extracellular fluids, including blood, lymphatic fluid, and cerebrospinal fluid, are collectively called body fluids. The Na+ concentration ([Na+]) in body fluids is maintained at 135-145 mM and is broadly conserved among terrestrial animals. Homeostatic osmoregulation by Na+ is vital for life because severe hyper- or hypotonicity elicits irreversible organ damage and lethal neurological trauma. To achieve "body fluid homeostasis" or "Na homeostasis", the brain continuously monitors [Na+] in body fluids and controls water/salt intake and water/salt excretion by the kidneys. These physiological functions are primarily regulated based on information on [Na+] and relevant circulating hormones, such as angiotensin II, aldosterone, and vasopressin. In this review, we discuss sensing mechanisms for [Na+] and hormones in the brain that control water/salt intake behaviors, together with the responsible sensors (receptors) and relevant neural pathways. We also describe mechanisms in the brain by which [Na+] increases in body fluids activate the sympathetic neural activity leading to hypertension.

SLC9A4 in the organum vasculosum of the lamina terminalis is a [Na+] sensor for the control of water intake.

Nax is a brain [Na+] sensor expressed in the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT) in the brain. We previously demonstrated that Nax signals are involved in the control of water intake behavior through the Nax/TRPV4 pathway. Nax gene knockout mice showed significantly attenuated water intake after an intracerebroventricular (ICV) injection of a hypertonic NaCl solution; however, the induction of a certain amount of water intake still remained, suggesting that another unknown [Na+]-dependent pathway besides the Nax/TRPV4 pathway contributes to water intake. In the present study, we screened for novel [Na+] sensors involved in water intake control and identified SLC9A4 (also called sodium (Na+)/hydrogen (H+) exchanger 4 (NHE4)). SLC9A4 is expressed in angiotensin II (Ang II) receptor type 1a (AT1a)-positive neurons in the OVLT. Sodium-imaging experiments using cultured cells transfected with slc9a4 revealed that SLC9A4 was activated by increases in extracellular [Na+] ([Na+]o), but not osmolality. Moreover, the firing activity of SLC9A4-positive neurons was enhanced by increases in [Na+]o and Ang II. slc9a4 knockdown in the OVLT reduced water intake induced by increases in [Na+], but not osmolality, in the cerebrospinal fluid. ICV injection experiments of a specific inhibitor suggested that the increase in extracellular [H+] caused by SLC9A4 activation next stimulates acid-sensing channel 1a (AS1C1a) to induce water intake. Our results thus indicate that SLC9A4 in the OVLT functions as a [Na+] sensor for the control of water intake and that the SLC9A4 signal is independent of the Nax/TRPV4 pathway.

Significant improvement in portal-systemic liver failure symptoms and successful management of portal-splenic venous hemodynamics by the combination of interventional radiology and pharmacotherapy.

This study describes a case of hepatitis C virus-related decompensated cirrhosis with portal-systemic liver failure and refractory encephalopathy. It was successfully managed with a combination of interventional radiology and pharmacotherapy, to improve hepatic function, including hyperammonemia and to control portal-splenic venous hemodynamics with hepatic venous pressure gradient (HVPG) monitoring. A man in his late 50s presented with a Child-Pugh score of 13, Model for End-Stage Liver Disease-sodium (MELD-Na) score of 19 and blood ammonia level of 185 µg/dL. He underwent balloon-occluded retrograde transvenous obliteration (BRTO) followed by partial splenic embolization (PSE) and non-selective beta-blocker (NSBB) administration. BRTO induced drastic changes in the portal-splenic venous hemodynamics, resulting in dramatically improved hepatic function and reduced hyperammonemia. However, the procedure resulted in increased HVPG from 13.6 mmHg at baseline to 23.5 mmHg at 1-month post-BRTO, accompanied by ascites retention and development of portal hypertensive gastropathy. Thereafter, PSE was performed, followed by NSBB administration, to control the elevated portal venous pressure following BRTO. Postoperatively, the patient's ascites and portal hypertensive gastrophy improved after splenic artery embolization, which eventually disappeared after the additional administration of NSBBs 1 month later. The HVPG finally decreased to 16.9 mmHg; the Child-Pugh score, MELD-Na score and blood ammonia level improved to 7, 11 and 22 µg/dL, respectively, after all therapies. BRTO significantly improved the symptoms of portal-systemic liver failure with refractory encephalopathy. PSE and NSBB administration could contribute to additional amelioration of hepatic function and successful management of complications induced by portal hemodynamic changes following BRTO.

Liver stiffness measured by transient elastography as predictor of prognoses following portosystemic shunt occlusion.

BACKGROUND AND AIM: This study aimed to identify predictors of model for end-stage liver disease sodium score reductions and improvements in vital prognoses following portosystemic shunt occlusion in portal hypertension patients. METHODS: Seventy cirrhotic patients with major portosystemic shunts and a mean model for end-stage liver disease sodium score of 10.5 underwent balloon-occluded retrograde transvenous obliteration between February 2008 and March 2017. We calculated the scores before and 1 month after shunt occlusion. The long-term outcomes were monitored, and vital prognoses were analyzed. RESULTS: The model for end-stage liver disease sodium score did not change significantly 1 month post-balloon-occluded retrograde transvenous obliteration, and the score decreased postoperatively in 31 (44.3%) patients. Univariate analyses showed that decline in the score after portosystemic shunt occlusion was strongly associated with hepatic encephalopathy as a procedural indication, lower liver volumes, and lower liver stiffness levels measured by transient elastography before treatment (P < 0.05). Multivariate logistic regression analysis identified preoperative liver stiffness level as an independent predictor of model for end-stage liver disease sodium score amelioration following balloon-occluded retrograde transvenous obliteration (P < 0.05), and receiver operating characteristic curve analysis determined a liver stiffness cutoff value of 21.6 kPa, with a sensitivity of 76.0% and specificity of 69.6%. The Kaplan-Meier method determined that overall survival rates after treatment in patients with liver stiffness < 21.6 kPa were significantly higher than in patients with liver stiffness ≥ 21.6 kPa (P < 0.05). CONCLUSIONS: Liver stiffness measured by transient elastography may predict improvements in model for end-stage liver disease sodium scores and in survival rates after portosystemic shunt occlusion in portal hypertension patients.

Comparison of patients with hepatic encephalopathy and those with gastric varices before and after balloon-occluded retrograde transvenous obliteration.

AIM: To compare the clinical characteristics of patients with hepatic encephalopathy (HE) and those with gastric varices (GV) before and after balloon-occluded retrograde transvenous obliteration (BRTO). METHODS: Eighty cirrhotic patients who underwent BRTO, including 42 men and 38 women, and whose mean age was 68 years, comprised the HE (n = 18) and GV (n = 62) groups. The patients' data before and 1 month after BRTO were analyzed. RESULTS: Before BRTO, the groups did not differ in their portal flow volume (PFV) or hepatic venous pressure gradient (HVPG). The portal vein (PV) was narrower and the splenic vein (SpV) was wider in the HE group than in the GV group. The SpV flow was hepatofugal in 75.0% of HE patients and hepatopetal in 92.6% of GV patients. The Child-Pugh (CP) score of the HE group was significantly higher than that of the GV group pre-BRTO. After BRTO, the PFV and HVPG increases in the HE group equaled those in the GV group, and the PV dilation was similar in both groups. Conversely, the SpV was significantly contracted for HE patients, but significantly dilated for GV patients. Postoperatively, the SpV flow was hepatopetal in all patients. Compared to that in the GV group, the CP score decreased markedly in the HE group, and no significant increases in complications occurred post-BRTO for HE patients. CONCLUSIONS: The HE patients showed distinct portal-splenic hemodynamics before and after BRTO. Balloon-occluded retrograde transvenous obliteration markedly improved hepatic function in the HE group compared with the GV group.

Plasma Glucose Level Is Predictive of Serum Ammonia Level After Retrograde Occlusion of Portosystemic Shunts.

OBJECTIVE: The purpose of this study was to evaluate predictors of reduction in ammonia levels by occlusion of portosystemic shunts (PSS) in patients with cirrhosis. MATERIALS AND METHODS: Forty-eight patients with cirrhosis (21 women, 27 men; mean age, 67.8 years) with PSS underwent balloon-occluded retrograde transvenous obliteration (BRTO) at one institution between February 2008 and June 2014. The causes of cirrhosis were hepatitis B in one case, hepatitis C in 20 cases, alcohol in 15 cases, nonalcoholic steatohepatitis in eight cases, and other conditions in four cases. The Child-Pugh classes were A in 24 cases, B in 23 cases, and C in one case. The indication for BRTO was gastric varices in 40 cases and hepatic encephalopathy in eight cases. Testing was conducted before and 1 month after the procedure. Statistical analyses were performed to identify predictors of a clinically significant decline in ammonia levels after BRTO. RESULTS: Occlusion of PSS resulted in a clinically significant decrease in ammonia levels accompanied by increased portal venous flow and improved Child-Pugh score. Univariate analyses showed that a reduction in ammonia levels due to BRTO was significantly related to lower plasma glucose levels, higher RBC counts, and higher hemoglobin concentration before the treatment. Furthermore, multivariate logistic regression identified preoperative plasma glucose level as the strongest independent predictor of a significant ammonia reduction in response to BRTO. In addition, although BRTO resulted in significantly declined ammonia levels in patients with normal glucose tolerance before the procedure, ammonia levels were not significantly decreased after shunt occlusion in patients with diabetes mellitus or impaired glucose tolerance before BRTO, according to 75-g oral glucose tolerance test results. CONCLUSION: Preoperative plasma glucose level is a useful predictor of clinically significant ammonia reduction resulting from occlusion of PSS in patients with cirrhosis. Even if PSS are present, control of blood ammonia levels by BRTO alone may be difficult in patients with glucose intolerance.

Development of a digital impression procedure using photogrammetry for complete denture fabrication.

OBJECTIVES: We developed an innovative procedure for digitizing maxillary edentulous residual ridges with a photogrammetric system capable of estimating three-dimensional (3D) digital forms from multiple two-dimensional (2D) digital images. The aim of this study was to validate the effectiveness of the photogrammetric system. MATERIALS AND METHODS: Impressions of the maxillary residual ridges of five edentulous patients were taken with four kinds of procedures: three conventional impression procedures and the photogrammetric system. Plaster models were fabricated from conventional impressions and digitized with a 3D scanner. Two 3D forms out of four forms were superimposed with 3D inspection software, and differences were evaluated using a least squares best fit algorithm. RESULTS: The in vitro experiment suggested that better imaging conditions were in the horizontal range of ± 15 degrees and at a vertical angle of 45 degrees. The mean difference between the photogrammetric image (Form A) and the image taken from conventional preliminarily impression (Form C) was 0.52 ± 0.22 mm. The mean difference between the image taken of final impression through a special tray (Form B) and Form C was 0.26 ± 0.06 mm. The mean difference between the image taken from conventional final impression (Form D) and Form C was 0.25 ± 0.07 mm. The difference between Forms A and C was significantly larger than the differences between Forms B and C and between Forms D and C. CONCLUSION: The results of this study suggest that obtaining digital impressions of edentulous residual ridges using a photogrammetric system is feasible and available for clinical use.

Part-Digitizing System of Impression and Interocclusal Record for Complete Denture Fabrication.

Few studies have reported the application of digital technology to removable dentures, particularly for the process of impression and interocclusal recording for complete denture fabrication. This article describes a part-digitizing system of impression and interocclusal records for complete denture fabrication. The denture foundation area in an edentulous mouth, including the border areas and residual ridge, is outlined by tracing the surfaces with a 3-D pen-type digitizer. Specialized trays for final impressions and interocclusal records were generated using computer-aided design and manufactured using the digital data. Final impression and interocclusal records were carried out using these specialized trays. The computer-aided method using preliminary digital impressions and specialized trays would be feasible for clinical use for complete denture fabrication.

Detection of LacZ-Positive Cells in Living Tissue with Single-Cell Resolution.

The LacZ gene, which encodes Escherichia coli ß-galactosidase, is widely used as a marker for cells with targeted gene expression or disruption. However, it has been difficult to detect lacZ-positive cells in living organisms or tissues at single-cell resolution, limiting the utility of existing lacZ reporters. Herein we present a newly developed fluorogenic ß-galactosidase substrate suitable for labeling live cells in culture, as well as in living tissues. This precisely functionalized fluorescent probe exhibited dramatic activation of fluorescence upon reaction with the enzyme, remained inside cells by anchoring itself to intracellular proteins, and provided single-cell resolution. Neurons labeled with this probe preserved spontaneous firing, which was enhanced by application of ligands of receptors expressed in the cells, suggesting that this probe would be applicable to investigate functions of targeted cells in living tissues and organisms.

Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994 Japanese healthy individuals for pharmacogenomics studies.

Japan Pharmacogenomics Data Science Consortium (JPDSC) has assembled a database for conducting pharmacogenomics (PGx) studies in Japanese subjects. The database contains the genotypes of 2.5 million single-nucleotide polymorphisms (SNPs) and 5 human leukocyte antigen loci from 2994 Japanese healthy volunteers, as well as 121 kinds of clinical information, including self-reports, physiological data, hematological data and biochemical data. In this article, the reliability of our data was evaluated by principal component analysis (PCA) and association analysis for hematological and biochemical traits by using genome-wide SNP data. PCA of the SNPs showed that all the samples were collected from the Japanese population and that the samples were separated into two major clusters by birthplace, Okinawa and other than Okinawa, as had been previously reported. Among 87 SNPs that have been reported to be associated with 18 hematological and biochemical traits in genome-wide association studies (GWAS), the associations of 56 SNPs were replicated using our data base. Statistical power simulations showed that the sample size of the JPDSC control database is large enough to detect genetic markers having a relatively strong association even when the case sample size is small. The JPDSC database will be useful as control data for conducting PGx studies to explore genetic markers to improve the safety and efficacy of drugs either during clinical development or in post-marketing.

Vacuum Surface Science Meets Heterogeneous Catalysis: Dehydrogenation of a Liquid Organic Hydrogen Carrier in the Liquid State.

Ultrahigh vacuum (UHV) surface science techniques are used to study the heterogeneous catalytic dehydrogenation of a liquid organic hydrogen carrier in its liquid state close to the conditions of real catalysis. For this purpose, perhydrocarbazole (PH), otherwise volatile under UHV, is covalently linked as functional group to an imidazolium cation, forming a non-volatile ionic liquid (IL). The catalysed dehydrogenation of the PH unit as a function of temperature is investigated for a Pt foil covered by a macroscopically thick PH-IL film and for Pd particles suspended in the PH-IL film, and for PH-IL on Au as inert support. X-ray photoelectron spectroscopy and thermal desorption spectroscopy allows us to follow in situ the catalysed transition of perhydrocarbazole to carbazole at technical reaction temperatures. The data demonstrate the crucial role of the Pt and Pd catalysts in order to shift the dehydrogenation temperature below the critical temperature of thermal decomposition.

Efficient Packaging of Plasmid DNA Using a pH Sensitive Cationic Lipid for Delivery to Hepatocytes.

Plasmid DNA (pDNA) is expected to be a new class of medicine for treating currently incurable diseases. To deliver these nucleic acids, we developed a liposomal delivery system we have called a multifunctional envelope-type nano device (MEND). In this report, we demonstrate that a MEND containing a pH-sensitive cationic lipid, YSK05 (YSK-MEND), efficiently delivered pDNA via systemic injection, and that its expression was highly dependent on the encapsulation state of the pDNA. In the preparation, the pH, ionic strength, and sodium chloride (NaCl) concentration of the lipid/pDNA mixture strongly affected the encapsulation efficiency of pDNA. Additionally, the transgene expression of luciferase in the liver by the injected YSK-MEND was dependent on the encapsulation state of pDNA rather than the nature of the YSK-MEND. Confocal laser scanning microscopy findings revealed that injection of the YSK-MEND led to homogenous gene expression in the liver compared to injection via the hydrodynamic tail vein (HTV). Concerning the safety of the YSK-MEND, a transient increase in the activity of liver enzymes was observed. However, no significant adverse events were observed. Taken together, the YSK-MEND represents a potentially attractive therapy for the treatment of various hepatic diseases.

[Full Recovery from Cardiopulmonary Arrest caused by Traumatic Asphyxia].

Traumatic asphyxia is a crush injury of the chest characterized by facial edema, cyanosis, conjunctival hemorrhage, and petechiae on the face and chest. The prognosis depends on the duration of chest compression and early cardiopulmonary resuscitation after cardiopulmonary arrest. Here we report a case of full recovery from cardiopulmonary arrest caused by traumatic asphyxia. The chest of a 56-year-old man was compressed by a machine while working. Immediately, his colleague started cardiopulmonary resuscitation, which was successful. When he was admitted to our hospital, his consciousness level was E1V2M2(Glasgow coma scale). Our treatment included therapeutic hypothermia, the duration of which was 24 hours at 34 °C. Rewarming his body to 36 °C took place over 48 hours. Thereafter, he recovered completely and was discharged on the 12th hospital day without neurologic sequela. Therapeutic hypothermia was possibly effective in this case.

Construction of an aptamer modified liposomal system targeted to tumor endothelial cells.

We describe herein the development of a high affinity and specific DNA aptamer as a new ligand for use in liposomal nanoparticles to target cultured mouse tumor endothelial cells (mTECs). Active targeted nanotechnology based drug delivery systems are currently of great interest, due to their potential for reducing side effects and facilitating the delivery of cytotoxic drugs or genes in a site specific manner. In this study, we report on a promising aptamer candidate AraHH036 that shows selective binding towards mTECs. The aptamer does not bind to normal cells, normal endothelial cells or tumor cells. Therefore, we synthesized an aptamer-polyethylene glycol (PEG) lipid conjugate and prepared aptamer based liposomes (ALPs) by the standard lipid hydration method. First, we quantified the higher capacity of ALPs to internalize into mTECs by incubating ALPs containing 1 mol%, 5 mol% and 10 mol% aptamer of total lipids and compared the results to those for unmodified PEGylated liposomes (PLPs). A confocal laser scanning microscope (CLSM) uptake study indicated that the ALPs were taken up more efficiently than PLPs. The measured Kd value of the ALPs was 142 nM. An intracellular trafficking study confirmed that most of the rhodamine labeled ALPs were taken up and co-localized with the green lysotracker, thus confirming that they were located in lysosomes. Finally, using an aptamer based proteomics approach, the molecular target protein of the aptamer was identified as heat shock protein 70 (HSP70). The results suggest that these ALPs offer promise as a new carrier molecule for delivering anti-angiogenesis drugs to tumor vasculature.

Two parabrachial Cck neurons involved in the feedback control of thirst or salt appetite.

Thirst and salt appetite are temporarily suppressed after water and salt ingestion, respectively, before absorption; however, the underlying neural mechanisms remain unclear. The parabrachial nucleus (PBN) is the relay center of ingestion signals from the digestive organs. We herein identify two distinct neuronal populations expressing cholecystokinin (Cck) mRNA in the lateral PBN that are activated in response to water and salt intake, respectively. The two Cck neurons in the dorsal-lateral compartment of the PBN project to the median preoptic nucleus and ventral part of the bed nucleus of the stria terminalis, respectively. The optogenetic stimulation of respective Cck neurons suppresses thirst or salt appetite under water- or salt-depleted conditions. The combination of optogenetics and in vivo Ca2+ imaging during ingestion reveals that both Cck neurons control GABAergic neurons in their target nuclei. These findings provide the feedback mechanisms for the suppression of thirst and salt appetite after ingestion.

Biopsychosocial Consideration of Ikigai in Older Adults in Japan through a Cross-Sectional Study.

Ikigai-a Japanese concept that includes elements such as life's purpose and meaning-has been reported to be associated with various systemic health conditions, such as the risk of developing physical dysfunction or death in older adults. However, there are no reports that comprehensively examine the psychological and social aspects of Ikigai. We attempted to clarify the characteristics of Ikigai by examining it from a biopsychosocial model using physical, psychological, and social perspectives through a cross-sectional study on sarcopenia, frailty and healthy life expectancy in a hilly and mountainous area of Japan. Koyadaira in Mima City, which is located in a hilly and mountainous region on Shikoku Island in Japan, was targeted. This cross-sectional study included 105 outpatients aged 65 and over, with an average age of 79.02 ± 6.91 years. Ikigai (self-rating score on a scale of 0 (no Ikigai) to 5 (the highest Ikigai)) participants' level of physical activity (the Physical Activity Scale for the Elderly, PASE), degree of depression (the Geriatric Depression-15 Scale, GDS-15), cognitive function (the Mini-Mental State Examination, MMSE) and social isolation (the abbreviated Lubben Social Network Scale, LSNS-6) was assessed. Significant positive correlations were found between PASE and MMSE. The LSNS-6 significantly correlated with the MMSE and GDS-15. In a path model, out of four paths from PASE, GDS-15, MMSE, and LSNS-6 to Ikigai, the path from the GDS-15 alone was significant (correlation coefficient -0.271, p < 0.01). The adaptability of this model was good. This study indicates that depressive status has a large impact on Ikigai, along with physical, cognitive, and social conditions; thus, it is appropriate to consider that an affective psychological status, such as depressive symptoms, is a fundamental condition for having Ikigai.