Longitudinal association between mental health and future antibiotic prescriptions in healthy adults: Results from the LOHAS

Objectives: To investigate the association of mental health and subjective physical functioning with future antibiotic prescriptions. Design: Prospective cohort study. Setting: A rural town in Japan. Participants: Participants who completed the baseline survey (2008-2010) of the Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study (LOHAS) were recruited. Participants were limited to those without comorbidities according to the Charlson comorbidity index. Participants using antibiotics at baseline were excluded. Mental health and physical functioning were assessed using the Mental Health and Physical Functioning domains of the Short-Form 12 Health Survey, and depressive symptoms were assessed using the Mental Health Inventories at baseline. Main outcome measures: The main outcome was antibiotic prescriptions found in claims data during 1 year after the baseline survey. Results: A total of 967 participants were included in the analysis, and 151 (15.6%) participants with at least one missing variable for the confounding factors were excluded, leaving 816 participants for the primary analysis. Among the 816 participants, 65 (8.0%) were newly prescribed at least one antibiotic during the 1-year follow-up period. The most frequently prescribed antibiotics were third-generation cephalosporins (44 prescriptions; 35.5%), macrolides (28 prescriptions; 22.6%), and quinolones (23 prescriptions; 18.6%). A multivariable logistic regression analysis showed an association between higher mental health scores and future antibiotic prescriptions (adjusted odds ratio [AOR], 1.40 per 1 standard deviation [SD] increase; 95% confidence interval [CI], 1.03-1.90), whereas no significant relationship was observed between Physical Functioning scores and future antibiotic prescriptions (AOR, 0.95 per 1 SD increase; 95% CI, 0.75-1.22). During the secondary analysis, adults with depressive symptoms were less likely to be prescribed antibiotics (AOR, 0.27; 95% CI, 0.11-0.70). Conclusions: Better mental health was associated with increased future antibiotic prescriptions for healthy community-dwelling Japanese adults, suggesting that mentally healthier adults could be a target population for reducing antimicrobial use

Geriatric Nutritional Risk Index (GNRI) and Creatinine Index Equally Predict the Risk of Mortality in Hemodialysis Patients: J-DOPPS

The geriatric nutritional risk index (GNRI) and creatinine (Cr) index are indexes often used as nutritional surrogates in patients receiving hemodialysis. However, few studies have directly compared the clinical characteristics of these two indexes. We investigated 3, 536 hemodialysis patients enrolled in the Japan DOPPS phases 4 and 5. The primary outcome was all-cause mortality and the main exposures were the GNRI and Cr index. We confirmed and compared the association between these indexes and mortality risk as estimated by a multivariable-adjusted Cox proportional hazards model. During the median 2.2-year follow-up period, 414 patients died of any cause. In the multivariable-adjusted model, lower GNRI and Cr index were both associated with increased risk of all-cause mortality, and these associations were further confirmed by restricted cubic spline curves. The predictability of all-cause mortality, as represented by the c-statistic, was comparable between the two indexes. Furthermore, baseline nutritional surrogates that corresponded with lower GNRI or Cr index values were comparable between the two indexes. Given that calculating the GNRI is simpler than calculating the Cr index, our data suggest that the GNRI may be preferable to the Cr index for predicting clinical outcomes in patients undergoing maintenance hemodialysis

Changes in Quality of Life in Older Hemodialysis Patients: A Cohort Study on Dialysis Outcomes and Practice Patterns

Background: Despite improvements in dialysis treatment, mortality rates remain high, especially among older hemodialysis patients. Quality of life (QOL) among hemodialysis patients is strongly associated with higher risk of death. This study aimed to describe the health-related QOL and its change in older maintenance hemodialysis patients and to demonstrate characteristics associated with health-related QOL. Methods: Data on 892 maintenance hemodialysis patients aged 60 years or older who were surveyed using the Kidney Disease Quality of Life Short Form at baseline and 2 years after study enrollment in phases 4 (2009–2011) and 5 (2012–2014) of the Japanese Dialysis Outcomes and Practice Patterns Study were analyzed. We categorized participants into 3 age groups (60–69, 70–79, and ≥80 years) and described baseline physical component summary (PCS) and mental component summary (MCS) scores, as well as their distribution of changes after 2 years across each category. Results: Hemodialysis patients aged 70–79 years and ≥80 years had lower PCS scores than those aged 60–69 years (median: 70–79 years = 43.1; interquartile range [IQR], 35.2–49.4; ≥80 years = 38.8; IQR, 31.6–43.8; 60–69 years = 45.4; IQR, 37.5–51.4; p < 0.001). In contrast, MCS scores did not significantly differ by age category (70–79 years = 45.6; IQR, 38.4–53.7; ≥80 years = 45.4; IQR, 36.9–55.1; 60–69 years = 46.8; IQR, 39.5–55.7; p = 0.1). As dialysis vintage lengthened, the PCS score significantly became lower, whereas no association was found with change in the MCS score. The MCS score declined over time in older patients, especially among those aged 80 years and older after 2 years’ follow-up. Conclusions: Physical QOL became worse as dialysis vintage lengthened. In contrast, mental QOL declined over time within a relatively short period among older maintenance hemodialysis patients

The CCR4–NOT Deadenylase Complex Maintains Adipocyte Identity

Shortening of poly(A) tails triggers mRNA degradation; hence, mRNA deadenylation regulates many biological events. In the present study, we generated mice lacking the Cnot1 gene, which encodes an essential scaffold subunit of the CCR4–NOT deadenylase complex in adipose tissues (Cnot1-AKO mice) and we examined the role of CCR4–NOT in adipocyte function. Cnot1-AKO mice showed reduced masses of white adipose tissue (WAT) and brown adipose tissue (BAT), indicating abnormal organization and function of those tissues. Indeed, Cnot1-AKO mice showed hyperinsulinemia, hyperglycemia, insulin resistance, and glucose intolerance and they could not maintain a normal body temperature during cold exposure. Muscle-like fibrous material appeared in both WAT and BAT of Cnot1-AKO mice, suggesting the acquisition of non-adipose tissue characteristics. Gene expression analysis using RNA-sequencing (RNA-seq) showed that the levels of adipose tissue-related mRNAs, including those of metabolic genes, decreased, whereas the levels of inflammatory response-related mRNAs increased. These data suggest that the CCR4–NOT complex ensures proper adipose tissue function by maintaining adipocyte-specific mRNAs at appropriate levels and by simultaneously suppressing mRNAs that would impair adipocyte function if overexpressed

CNOT1 regulates circadian behaviour through Per2 mRNA decay in a deadenylation-dependent manner

Circadian clocks are an endogenous internal timekeeping mechanism that drives the rhythmic expression of genes, controlling the 24 h oscillatory pattern in behaviour and physiology. It has been recently shown that post-transcriptional mechanisms are essential for controlling rhythmic gene expression. Controlling the stability of mRNA through poly(A) tail length modulation is one such mechanism. In this study, we show that Cnot1, encoding the scaffold protein of the CCR4-NOT deadenylase complex, is highly expressed in the suprachiasmatic nucleus, the master timekeeper. CNOT1 deficiency in mice results in circadian period lengthening and alterations in the mRNA and protein expression patterns of various clock genes, mainly Per2. Per2 mRNA exhibited a longer poly(A) tail and increased mRNA stability in Cnot1+/− mice. CNOT1 is recruited to Per2 mRNA through BRF1 (ZFP36L1), which itself oscillates in antiphase with Per2 mRNA. Upon Brf1 knockdown, Per2 mRNA is stabilized leading to increased PER2 expression levels. This suggests that CNOT1 plays a role in tuning and regulating the mammalian circadian clock.journal articl

Usefulness of laparoscopic subtotal cholecystectomy with operative cholangiography for severe cholecystitis

PURPOSE: Cholecystectomy can become hazardous when inflammation develops, leading to anatomical changes in Calot’s triangle. We attempted to study the safety and efficacy of laparoscopic subtotal cholecystectomy (LSC) to decrease the incidence of complications and the rate of conversion to open surgery. METHODS: Patients who underwent LSC between January 2005 and December 2008 were evaluated retrospectively. The operations were performed laparoscopically irrespective of the grade of inflammation estimated preoperatively. However, patients with severe inflammation of the gallbladder underwent LSC involving resection of the anterior wall of the gallbladder, removal of all stones and placement of an infrahepatic drainage tube. To prevent intraoperative complications, including bile duct injury, intraoperative cholangiography was performed. RESULTS: LSC was performed in 26 elective procedures among 26 patients (eight females, 18 males). The median patient age was 69 years (range 43–82 years). The median operative time was 125 min (range 60–215 min) and the median postoperative inpatient stay was 6 days (range 3–21 days). Cholangiography was performed during surgery in 24 patients. One patient underwent postoperative endoscopic sphincterotomy for a retained common bile duct stone that was found on cholangiography during surgery. Neither complications nor conversion to open surgery were encountered in this study. CONCLUSIONS: LSC with the aid of intraoperative cholangiography is a safe and effective treatment for severe cholecystitis

True Carcinosarcoma of the Esophagus: Report of a Case

Carcinosarcoma of the esophagus is a malignant neoplasm involving both carcinomatous and sarcomatous components. We report a patient with true esophageal carcinosarcoma who underwent laparoscopy-assisted surgery. An upper gastrointestinal barium study revealed a lobulated intraluminal filling defect in the lower intrathoracic esophagus. The patient underwent esophagectomy and regional lymphadenectomy with gastric tube reconstruction by laparoscopy-assisted surgery and thoracotomy. The esophageal hiatus was entered and the mediastinal esophagus was dissected using a laparoscopic approach. Microscopically, the tumor comprised poorly differentiated squamous cell carcinoma and spindle-shaped cells resembling leiomyosarcoma. Immunohistochemically, spindle-shaped sarcomatous cells displayed strongly positive reaction to vimentin and negative reaction to cytokeratin AE1/AE3 and CD68. No transitional zone was seen between sarcomatous and carcinomatous elements. The patient was finally diagnosed with true esophageal carcinosarcoma. Laparoscopic transhiatal esophagectomy seems to be a rational and safe procedure for lower esophageal neoplasms, even for patients with impaired respiratory function

ARE-binding protein ZFP36L1 interacts with CNOT1 to directly repress translation via a deadenylation-independent mechanism

Eukaryotic gene expression can be spatiotemporally tuned at the post-transcriptional level by cis-regulatory elements in mRNA sequences. An important example is the AU-rich element (ARE), which induces mRNA destabilization in a variety of biological contexts in mammals and can also mediate translational control. Regulation is mediated by trans-acting factors that recognize the ARE, such as Tristetraprolin (TTP) and BRF1/ZFP36L1. Although both proteins can destabilize their target mRNAs through the recruitment of the CCR4-NOT deadenylation complex, TTP also directly regulates translation. Whether ZFP36L1 can directly repress translation remains unknown. Here, we used an in vitro translation system derived from mammalian cell lines to address this key mechanistic issue in ARE regulation by ZFP36L1. Functional assays with mutant proteins reveal that ZFP36L1 can repress translation via AU-Rich elements independent of deadenylation. ZFP36L1-mediated translation repression requires interaction between ZFP36L1 and CNOT1, suggesting that it might use a repression mechanism similar to either TPP or miRISC. However, several lines of evidence suggest that the similarity ends there. Unlike, TTP, it does not efficiently interact with either 4E-HP or GIGYF2, suggesting it does not repress translation by recruiting these proteins to the mRNA cap. Moreover, ZFP36L1 could not repress ECMV-IRES driven translation and was resistant to pharmacological eIF4A inhibitor silvestrol, suggesting fundamental differences with miRISC repression via eIF4A. Collectively, our results reveal that ZFP36L1 represses translation directly and suggest that it does so via a novel mechanism distinct from other translational regulators that interact with the CCR4-NOT deadenylase complex

The CCR4–NOT complex maintains liver homeostasis through mRNA deadenylation

The biological significance of deadenylation in global gene expression is not fully understood. Here, we show that the CCR4-NOT deadenylase complex maintains expression of mRNAs, such as those encoding transcription factors, cell cycle regulators, DNA damage response-related proteins, and metabolic enzymes, at appropriate levels in the liver. Liver-specific disruption of Cnot1, encoding a scaffold subunit of the CCR4-NOT complex, leads to increased levels of mRNAs for transcription factors, cell cycle regulators, and DNA damage response-related proteins because of reduced deadenylation and stabilization of these mRNAs. CNOT1 suppression also results in an increase of immature, unspliced mRNAs (pre-mRNAs) for apoptosis-related and inflammation-related genes and promotes RNA polymerase II loading on their promoter regions. In contrast, mRNAs encoding metabolic enzymes become less abundant, concomitant with decreased levels of these pre-mRNAs. Lethal hepatitis develops concomitantly with abnormal mRNA expression. Mechanistically, the CCR4-NOT complex targets and destabilizes mRNAs mainly through its association with Argonaute 2 (AGO2) and butyrate response factor 1 (BRF1) in the liver. Therefore, the CCR4-NOT complex contributes to liver homeostasis by modulating the liver transcriptome through mRNA deadenylation

A Retrospective Study in the Diagnosis of 301 Jaundiced Cases

In the past 12 years, 301 patients with a total serum bilirubin over 2 mg/dl (reference interval 0.2-0.8 mg/dl) were admitted to the Second Department of Surgery, Nagasaki University School of Medicine, Japan. The purpose of this paper is to analyse the jaundiced cases and to evaluate the diagnostic accuracy of the following imaging techniques: Computed Tomography (CT), Ultrasonography (US), Drip Infusion Cholangiography (DIC), Endoscopic Retrograde Cholangio- pancreatography (ERCP), Percutaneous transhepatic Cholangiography (PTC) and Selective Celiac Angiography (SCAG). Of the 301 patients, 63 had carcinoma of the bile duct, 48 carcinoma of the pancreas, 26 carcinoma of the gallbladder, 16 hepatoma, 8 carcinoma of the ampulla of Vater, 83 cholelithiasis, 27 parenchymal liver disease, 9 congenital bile duct disease, 5 chronic pancreatitis, 14 other diseases, and 2 had no final diagnosis. CT was attempted in 33 of 170 patients with malignancy, and 22 of 129 patients with benignancy. A correct finding was obtained in 23 (69.7%) of the 33 patients and 18 (81.8%) of the 22 patients, respectively. US gave a correct finding in 28 (59.6 %) of 47 patients with malignancy, and 36 (69.2%) of 52 patients with benignancy. DIC gave a correct finding in 1 (5.6%) of 18 patients with malignancy, and 16 (42.1%) of 38 patients with benignancy. ERCP gave a correct finding in 33 (76.7%) of 43 patients with malignancy, and 38 (74.5%) of 51 patients with benignancy. PTC gave a correct finding i