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.

Organizing Pneumonia in a Case of cold Agglutinin Disease with Pulmonary Thrombosis.

Cold agglutinin disease is a subtype of autoimmune hemolytic anemia that occurs via the activation of specific anti-red blood cell antibodies (agglutinins) at low temperatures. Autoimmune hemolytic anemia has been reported to cause interstitial pneumonia; however, the underlying mechanism remains unclear. We herein report a 46-year-old man diagnosed with cold agglutinin disease complicated by pulmonary thrombosis and organizing pneumonia. Treatment with prednisolone improved the course of cold agglutinin disease and organizing pneumonia in a similar manner. To our knowledge, this is the first report of cold agglutinin associated with organizing pneumonia, suggesting a potential link between the two.

Early Prediction of Response Focused on Tumor Markers in Atezolizumab plus Bevacizumab Therapy for Hepatocellular Carcinoma.

Despite the promising efficacy of atezolizumab plus bevacizumab (atezo/bev), some patients with unresectable hepatocellular carcinoma (HCC) experience disease progression. This retrospective study, which included 154 patients, aimed to evaluate predictors of treatment efficacy of atezo/bev for unresectable HCC. Factors associated with treatment response were examined, focusing on tumor markers. In the high-alpha-fetoprotein (AFP) group (baseline AFP ≥ 20 ng/mL), a decrease in AFP level > 30% was an independent predictor of objective response (odds ratio, 5.517; p = 0.0032). In the low-AFP group (baseline AFP < 20 ng/mL), baseline des-gamma-carboxy prothrombin (DCP) level < 40 mAU/mL was an independent predictor of objective response (odds ratio, 3.978; p = 0.0206). The independent predictors of early progressive disease were an increase in AFP level ≥ 30% at 3 weeks (odds ratio, 4.077; p = 0.0264) and the presence of extrahepatic spread (odds ratio, 3.682; p = 0.0337) in the high-AFP group and up-to-seven criteria, OUT (odds ratio, 15.756; p = 0.0257) in the low-AFP group. In atezo/bev therapy, focusing on early AFP changes, baseline DCP, and tumor burden of up-to-seven criteria are useful in predicting response to treatment.

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.

Novel Magnetic Attachment System Manufactured Using High-Frequency Heat Treatment and Stamp Technique: Introduction and Basic Performance.

Recently, a novel magnetic attachment with extremely low cost and high performance was developed. This article aims to introduce a novel magnetic attachment and to evaluate its basic eligibility for denture retention in clinical practice. The novel magnetic attachment system used in this study was the direct-bonding root-keeper-type Magteeth™ MT800 (MagneDesign, Nagoya, Japan). The retentive force without displacement (position 0) and after horizontal displacement to positions 0.5, 1, 1.5, 2, 2.5, and 3 mm were measured. The values relative to the retentive force without displacement were gradually decreased to 82.7 ± 16.3%, 68.8 ± 17.1%, 62.4 ± 15%, 47.2 ± 13.1%, 35.7 ± 9.9%, and 20.7 ± 6.5%, respectively. The retentive force and magnetic field strength did not change significantly after the load test (100 N load, 10,000 times). No new gap between the metal and resin was found in the root keeper- and magnet assembly-embedded blocks after the load test. Some scratches on magnetic assembly and root keeper surface, while no change in the resin texture after the load test were observed. Based on the findings of this preliminary study, this novel low-cost magnetic attachment exhibited favorable retention, strength, and durability for clinical use.

Effect of the enantiomeric structure of hydrophobic polymers on the encapsulation properties of a second near infrared (NIR-II) fluorescent dye for in vivo deep imaging.

Over-thousand-nanometer (OTN) near-infrared (NIR) fluorophores are useful for biological deep imaging because of the reduced absorption and scattering of OTN-NIR light in biological tissues. IR-1061, an OTN-NIR fluorescent dye, has a hydrophobic and cationic backbone in its molecular structure, and a non-polar counter ion, BF4 -. Because of its hydrophobicity, IR-1061 needs to be encapsulated in a hydrophobic microenvironment, such as a hydrophobic core of polymer micelles, shielded with a hydrophilic shell for bioimaging applications. Previous studies have shown that the affinity of dyes with hydrophobic core polymers is dependent on the polarity of the core polymer, and that this characteristic is important for designing dye-encapsulated micelles to be used in bioimaging. In this study, the dye-polymer affinity was investigated using hydrophobic polymer films with different chiral structures of poly(lactic acid). IR-1061 showed higher affinity for l- and d-lactic acid copolymers (i.e., poly(dl-lactic acid) (PDLLA)) than to poly(l-lactic acid) (PLLA), as IR-1061 shows less dimerization in PDLLA than in PLLA. In contrast, the stability of IR-1061 in PDLLA was less than that in PLLA due to the influence of hydroxyl groups. Choosing hydrophobic core polymers for their robustness and dye affinity is an effective strategy to prepare OTN-NIR fluorescent probes for in vivo deep imaging.

Drastic Improvement in Hepatitis B/C Virus-induced Decompensated Liver Cirrhosis Treated by Total Management Consisting of Interventional Radiology, Endoscopy, and Pharmacotherapy.

Recent advances in antiviral therapy have enabled control of the hepatitis virus; however, these do not completely eliminate the pathological condition of liver disease, and portal hypertension remains a clinical problem. We herein report a case of hepatitis B virus/hepatitis C virus (HBV/HCV)-induced decompensated liver cirrhosis for which total management consisting of interventional radiology and endoscopy, based on the evidence of our clinical studies, followed by antiviral therapy for co-infection with HBV and HCV was successful. This case clearly indicates the effective timing of total management, suggesting that it prolongs the vital prognosis in addition to improving the hepatic function.

Effects of hydrophilic/hydrophobic blocks ratio of PEG-b-PLGA on emission intensity and stability of over-1000 nm near-infrared (NIR-II) fluorescence dye-loaded polymeric micellar nanoparticles.

Polymeric micellar nanoparticles (PNPs) composed of an amphiphilic block copolymer formed from hydrophilic and hydrophobic blocks and over-thousand-nanometer (OTN) near-infrared (NIR) fluorescent dye are promising fluorophores for the dynamic imaging of deep tissue. In this study, we examined the effect of the ratio of hydrophilic/hydrophobic blocks of a block copolymer, poly(ethylene glycol) (PEG)-b-poly(lactide-co-glycolide) (PLGA), on the properties of OTN-PNPs encapsulating IR-1061. OTN-PNPs with a higher molecular weight of PLGA cores showed higher emission and stabilities under physiological conditions. The PEG ratio to PLGA in the block copolymer decreased the stability of OTN-PNPs probably due to the invasion of water molecules into the polymer core. The results show that the in vivo stability and fluorescence properties can be tuned by adjusting the chain lengths of block copolymers and estimated using in vitro assays, which evaluates the brightness retention rate of the OTN-PNPs under physiological conditions.

Application of artificial intelligence in the dental field: A literature review.

PURPOSE: The purpose of this study was to comprehensively review the literature regarding the application of artificial intelligence (AI) in the dental field, focusing on the evaluation criteria and architecture types. STUDY SELECTION: Electronic databases (PubMed, Cochrane Library, Scopus) were searched. Full-text articles describing the clinical application of AI for the detection, diagnosis, and treatment of lesions and the AI method/architecture were included. RESULTS: The primary search presented 422 studies from 1996 to 2019, and 58 studies were finally selected. Regarding the year of publication, the oldest study, which was reported in 1996, focused on "oral and maxillofacial surgery." Machine-learning architectures were employed in the selected studies, while approximately half of them (29/58) employed neural networks. Regarding the evaluation criteria, eight studies compared the results obtained by AI with the diagnoses formulated by dentists, while several studies compared two or more architectures in terms of performance. The following parameters were employed for evaluating the AI performance: accuracy, sensitivity, specificity, mean absolute error, root mean squared error, and area under the receiver operating characteristic curve. CONCLUSION: Application of AI in the dental field has progressed; however, the criteria for evaluating the efficacy of AI have not been clarified. It is necessary to obtain better quality data for machine learning to achieve the effective diagnosis of lesions and suitable treatment planning.

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.

A case of COVID-19 with superficial thrombophlebitis caused by an indwelling peripheral venous catheter.

A local hypercoagulable state caused by SARS-CoV-2 and an indwelling peripheral venous catheter can lead to superficial thrombophlebitis. If the venous catheter is no longer needed during treatment for COVID-19 it should be removed promptly.

Isolation of balenine from opah (Lampris megalopsis) muscle and comparison of antioxidant and iron-chelating activities with other major imidazole dipeptides.

Balenine (Bal) in opah muscle was extracted using hot water and purified by ion-exchange chromatography and recrystallization to provide 41 g of over 95% pure Bal from 1 kg of opah muscle. The structure of purified Bal was identical to that of an authentic Bal standard by NMR analysis. The antioxidant (ORAC and HORAC values) and Fe(II) ion-chelating abilities of purified Bal were examined by comparison with two major imidazole dipeptides, carnosine (Car) and anserine (Ans). Opah-derived Bal showed significantly higher ORAC and HORAC values and Fe(II) ion-chelating ability at 0.3 mM. In silico molecular simulation revealed that Bal and Car formed hydrogen bonds between the hydrogen atom of the imidazole imino group and the carboxyl carbonyl oxygen, whereas Ans did not. The proposed method for extracting and purifying Bal from opah muscle suggests that opah can be utilized as a functional food or Bal resource.

Splenic non-infarction volume determines a clinically significant hepatic venous pressure gradient response to partial splenic embolization in patients with cirrhosis and hypersplenism.

BACKGROUND: This study aimed to investigate changes in the hepatic venous pressure gradient (HVPG) by partial splenic embolization (PSE) and to identify the determinants of a clinically meaningful postoperative HVPG reduction. METHODS: Sixty-eight patients with cirrhosis and hypersplenism who underwent PSE at our department between September 2007 and June 2020 were included. The HVPG was evaluated pre- and immediately post-PSE. The patients were divided into three groups according to their preprocedural HVPG: low-HVPG (< 10 mmHg, n = 22), intermediate-HVPG (10 mmHg ≤ HVPG < 16 mmHg, n = 33), and high-HVPG (≥ 16 mmHg, n = 13). RESULTS: Overall, PSE significantly reduced HVPG from 12.2 ± 4.0 to 9.4 ± 3.6 mmHg (p < 0.01) with a relative decrease of 22.2 ± 20.4%. In addition, HVPG reductions were 19.4 ± 28.7%, 24.0 ± 15.9%, and 22.5 ± 13.3% in the low-, intermediate-, and high-HVPG groups, respectively, indicating no significant difference in HVPG reduction between the groups. An HVPG decrease of ≥ 20% from the baseline, defined in this study as a clinically significant HVPG response to PSE, was achieved in 55.9% of all patients. Multivariate logistic regression and receiver operating characteristic curve analyses identified splenic non-infarction volume as an independent determinant of a 20% decrease in HVPG (p < 0.05), with a cut-off of 139.2 cm3 (sensitivity, 76.3%; specificity, 60.0%; p < 0.05). CONCLUSIONS: The splenic non-infarction volume, namely the residual functional spleen volume, independently determines a clinically significant HVPG response to PSE in patients with cirrhosis and hypersplenism.

Short-term Effects of Hepatic Arterial Buffer Responses Induced by Partial Splenic Embolization on the Hepatic Function of Patients with Cirrhosis According to the Child-Pugh Classification.

Objective This study primarily aimed to investigate the short-term effects of partial splenic embolization (PSE) on the Child-Pugh score and identify predictive factors for changes in the score caused by PSE. The secondary aim was to analyze changes in various parameters at one month postoperatively using these identified factors. Methods Between September 2007 and December 2019, 118 patients with cirrhosis and hypersplenism underwent PSE at our hospital. Testing was conducted preoperatively and at one month after PSE. Results Overall, the Child-Pugh score was not significantly changed postoperatively. The Child-Pugh score before PSE was identified as the strongest independent predictor of ameliorated and deteriorated Child-Pugh scores after PSE. Higher pretreatment Child-Pugh scores were correlated with higher posttreatment amelioration rates of the score. A significant decrease in the portal vein diameter and a significant increase in the common hepatic artery diameter were evident at the same level postoperatively in 64 patients with Child-Pugh class A (group A) and in 54 patients with Child-Pugh class B or C (group B/C) preoperatively. According to Murray's Law, PSE resulted in decreased portal venous flow and increased hepatic arterial flow, suggesting a hepatic arterial buffer response (HABR) induced by the procedure. Despite equivalent splenic infarction rates and similar posttreatment changes in hepatic hemodynamics, PSE significantly increased the Child-Pugh score of group A; however, the procedure significantly decreased the score of group B/C. Conclusion Considering original portal venous-hepatic arterial hemodynamics, PSE is expected to produce HABR-mediated hepatic functional improvements in cirrhosis patients with Child-Pugh class B/C.

Design of Over-1000 nm Near-Infrared Fluorescent Polymeric Micellar Nanoparticles by Matching the Solubility Parameter of the Core Polymer and Dye.

Polymeric micellar nanoparticles (PNPs) encapsulating over-thousand-nanometer (OTN) near-infrared (NIR) fluorescent dye molecules in block polymers having hydrophobic and hydrophilic chains are promising agents for the dynamic imaging of deep tissue. To achieve OTN-NIR fluorescent PNPs (OTN-PNPs) having high brightness, it is crucial to increase the affinity between the core polymer and dye molecules by matching their polarities; thus, criteria and methods to evaluate the affinity are required. In this study, we used the Hansen solubility parameter (HSP), including the polarity term, to evaluate the affinity between the two substances. HSP values of the OTN-NIR fluorescent dye IR-1061 and four core polymers, poly(lactic-co-glycolic acid) (PLGA), poly(lactic acid) (PLA), poly(ε-caprolactone) (PCL), and polystyrene (PSt), were calculated using the Hansen solubility sphere method and molecular group contribution method, respectively. The relative energy density between IR-1061 and each core polymer calculated using their HSP values revealed that the affinities of PLGA and PLA for IR-1061 are higher than those of PCL and PSt. Therefore, OTN-PNPs composed of PLGA, PLA, and PCL core polymers were prepared and compared. The OTN-PNPs having PLGA and PLA cores could be loaded with larger amounts of IR-1061, had higher photoluminescence intensities, and showed higher stability in phosphate buffered saline than those having PCL cores. Moreover, the OTN-PNPs having PLGA or PLA cores were used for the dynamic imaging of live mice. Thus, matching the solubility parameters of the core polymer and dye molecule is a useful approach for designing high-performance OTN-NIR fluorescent probes.

Correlation analysis of the proportion of monocytic myeloid-derived suppressor cells in colorectal cancer patients.

Monocytic myeloid-derived suppressor cells (mMDSCs) are a class of immunosuppressive immune cells with prognostic value in many solid tumors. It is reported that the proportion of mMDSCs in the peripheral blood can be a predictive marker for response to cancer immunotherapy. In this study, we performed a correlation analysis of the proportion of mMDSCs in freshly-drawn peripheral blood, levels of plasma proteins, and demographic factors in colorectal cancer (CRC) patients, to find factors that could be used to predict mMDSC proportions. Freshly-drawn mMDSCs were measured using flow cytometry on peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 24) and CRC patients (n = 78). The plasma concentrations of 29 different cytokines, chemokines, growth factors, and enzymes were measured using a multiplex assay or enzyme-linked immunosorbent assay. Correlation analysis to find mMDSC-associated factors was conducted using univariate and multivariate models. In univariate correlation analysis, there were no plasma proteins that were associated with mMDSC proportions in CRC patients. In multivariate analysis, considering all variables including age, sex, and plasma proteins, levels of inducible nitric acid synthase (iNOS) (p = 0.013) and platelet-derived growth factor (PDGF)-BB (p = 0.035) were associated with mMDSC proportion in PBMCs (mMDSC proportion [%] = 0.2929 - 0.2389 * PDGF-BB + 0.3582 * iNOS) (p < 0.005, r = 0.32). Measuring the plasma concentrations of iNOS and PDGF-BB may be useful in predicting the proportion of mMDSCs in CRC patients' peripheral blood. Further research is required to establish and validate these predictive factors. Data registration Patient data were registered in an anonymization system at Tsukuba Clinical Research & Development Organization (T-CReDO).

Distinct CCK-positive SFO neurons are involved in persistent or transient suppression of water intake.

The control of water-intake behavior is critical for life because an excessive water intake induces pathological conditions, such as hyponatremia or water intoxication. However, the brain mechanisms controlling water intake currently remain unclear. We previously reported that thirst-driving neurons (water neurons) in the subfornical organ (SFO) are cholecystokinin (CCK)-dependently suppressed by GABAergic interneurons under Na-depleted conditions. We herein show that CCK-producing excitatory neurons in the SFO stimulate the activity of GABAergic interneurons via CCK-B receptors. Fluorescence-microscopic Ca2+ imaging demonstrates two distinct subpopulations in CCK-positive neurons in the SFO, which are persistently activated under hyponatremic conditions or transiently activated in response to water drinking, respectively. Optical and chemogenetic silencings of the respective types of CCK-positive neurons both significantly increase water intake under water-repleted conditions. The present study thus reveals CCK-mediated neural mechanisms in the central nervous system for the control of water-intake behaviors.

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.