Transient demographic dynamics of recovering fish populations shaped by past climate variability, harvest, and management.

Large-scale commercial harvesting and climate-induced fluctuations in ocean properties shape the dynamics of marine populations as interdependent drivers at varied timescales. Persistent selective removals of larger, older members of a population can distort its demographic structure, eroding resilience to fluctuations in habitat conditions and thus amplifying volatility in transient dynamics. Many historically depleted marine fish stocks have begun showing signs of recovery in recent decades following the implementation of stricter management measures. But these interventions coincide with accelerated changes in the oceans triggered by increasingly warmer, more variable climates. Applying multilevel models to annual estimates of demographic metrics of 38 stocks comprising 11 species across seven northeast Atlantic ecoregions, this study explores how time-varying local and regional climates contributed to the transient dynamics of recovering populations exposed to variable fishing pressures moderated by management actions. Analyses reveal that progressive reductions in fishing pressure and shifting climate conditions discontinuously shaped rebuilding patterns of the stocks through restorations of maternal demographic structure (reversing age truncation) and reproductive capacity. As the survival rate and demographic structure of reproductive fish improved, transient growth became less sensitive to variability in recruitment and juvenile survival and more to that in adult survival. As the biomass of reproductive fish rose, recruitment success also became increasingly regulated by density-dependent processes involving higher numbers of older fish. When reductions in fishing pressure were insufficient or delayed, however, stocks became further depleted, with more eroded demographic structures. Although warmer local climates in spawning seasons promoted recruitment success in some ecoregions, changing climates in recent decades began adversely affecting reproductive performances overall, amplifying sensitivities to recruitment variability. These shared patterns underscore the value of demographic transients in developing robust strategies for managing marine resources. Such strategies could form the foundation for effective applications of adaptive measures resilient to future environmental change.

Tradeoffs of managing cod as a sustainable resource in fluctuating environments.

Sustainable human exploitation of living marine resources stems from a delicate balance between yield stability and population persistence to achieve socioeconomic and conservation goals. But our imperfect knowledge of how oceanic oscillations regulate temporal variation in an exploited species can obscure the risk of missing management targets. We illustrate how applying a management policy to suppress fluctuations in fishery yield in variable environments (prey density and regional climate) can present unintended outcomes in harvested predators and the sustainability of harvesting. Using Atlantic cod (Gadus morhua, an apex predatory fish) in the Barents Sea as a case study we simulate age-structured population and harvest dynamics through time-varying, density-dependent and density-independent processes with a stochastic, process-based model informed by 27-year monitoring data. In this model, capelin (Mallotus villosus, a pelagic forage fish), a primary prey of cod, fluctuations modulate the strength of density-dependent regulation primarily through cannibalistic pressure on juvenile cod survival; sea temperature fluctuations modulate thermal regulation of cod feeding, growth, maturation, and reproduction. We first explore how capelin and temperature fluctuations filtered through cod intrinsic dynamics modify catch stability and then evaluate how management to suppress short-term variability in catch targets alters overharvest risk. Analyses revealed that suppressing year-to-year catch variability impedes management responses to adjust fishing pressure, which becomes progressively out of sync with variations in cod abundance. This asynchrony becomes amplified in fluctuating environments, magnifying the amplitudes of both fishing pressure and cod abundance and then intensifying the density-dependent regulation of juvenile survival through cannibalism. Although these transient dynamics theoretically give higher average catches, emergent, quasicyclic behaviors of the population would increase long-term yield variability and elevate overharvest risk. Management strategies that overlook the interplay of extrinsic (fishing and environment) and intrinsic (life history and demography) fluctuations thus can inadvertently destabilize fish stocks, thereby jeopardizing the sustainability of harvesting. These policy implications underscore the value of ecosystem approaches to designing management measures to sustainably harvest ecologically connected resources while achieving socioeconomic security.

Fishing down then up the food web of an invaded lake.

Analysis of commercial catches reveals a serial depletion of some oceanic fish stocks over time, resulting in fisheries focusing on increasingly smaller species closer to the base of the food chain. This effect, described as fishing down the marine food web, is observed when the trophic level of the catch declines over time, raising concerns about the ecosystem impacts of fishing. Freshwater systems also experience harvest, yet do not appear to commonly show the same fishing down response perhaps because time series are too short to witness early depletions, fishing is often recreational, or other factors like stocking and invasive species influence patterns. Here we make use of extensive catch records from Lake Simcoe dating back to the 1860s, to examine if fishing down effects are observed in this highly exploited Canadian inland lake. We measured 2 commonly used indicators from catch data, mean trophic level (MTL) and fishing-in-balance (FiB), and compared trends between a historical period dominated by commercial fishing and a contemporary period when commercial fishing ceased and recreational fishing effort increased. We found a striking difference between the 2 time periods, with MTL (and to some extent FiB) declining during commercial fishing but increasing during recreational fishing. However, indicators either increased or decreased due to invasive species and increased due to stocking. We show that while declining MTL can occur in a freshwater lake, the trajectory can be altered by a switch to recreational fishing, as well as stocking and invasive species.

Endoscopic placement of covered versus uncovered self-expandable metal stents for palliation of malignant gastric outlet obstruction.

OBJECTIVE: Stenting is an established endoscopic therapy for malignant gastric outlet obstruction (mGOO). The choice of stent (covered vs uncovered) has been examined in prior randomised studies without clear results. DESIGN: In a multicentre randomised prospective study, we compared covered (CSEMS) with uncovered self-expandable metal stents (UCSEMS) in patients with mGOO; main outcomes were stent dysfunction and patient survival, with subgroup analyses of patients with extrinsic and intrinsic tumours. RESULTS: Overall survival was poor with no difference between groups (probability at 3 months 49.7% for covered vs 48.4% for uncovered stents; log-rank for overall survival p=0.26). Within that setting of short survival, the proportion of stent dysfunction was significantly higher for uncovered stents (35.2% vs 23.4%, p=0.01) with significantly shorter time to stent dysfunction. This was mainly relevant for patients with extrinsic tumours (stent dysfunction rates for uncovered stents 35.6% vs 17.5%, p<0.01). Subgrouping was also relevant with respect to tumour ingrowth (lower with covered stents for intrinsic tumours; 1.6% vs 27.7%, p<0.01) and stent migration (higher with covered stents for extrinsic tumours: 15.3% vs 2.5%, p<0.01). CONCLUSIONS: Due to poor patient survival, minor differences between covered and uncovered stents may be less relevant even if statistically significant; however, subgroup analysis would suggest to use covered stents for intrinsic and uncovered stents for extrinsic malignancies.

Initial predictors of skin thickness progression in patients with diffuse cutaneous systemic sclerosis: Results from a multicentre prospective cohort in Japan.

OBJECTIVE: To identify initial parameters that predict worsening of skin thickening in patients with diffuse cutaneous systemic sclerosis (dcSSc) using a multicentre, prospective, observational cohort in Japan. METHODS: A total of 171 patients with dcSSc were selected from a prospective cohort database based on the following criteria: dcSSc, modified Rodnan total skin thickness score (mRSS) ≥7, disease duration <60 months, and valid mRSS data at one year. Worsening of skin thickness was defined as an increase in mRSS ≥3 points and an increase ≥25% from baseline to one year. Initial demographic and clinical parameters useful for predicting the progression of skin thickness were identified using univariate and multivariable analysis, and prediction models of skin thickening progression were built based on combinations of independent predictive parameters. RESULTS: Only 23 patients (13.5%) experienced worsening mRSSs at one year. Short disease duration, low mRSS, absence of nailfold bleeding, arthritis, and a high erythrocyte sedimentation rate at diagnosis were identified as predictors of subsequent worsening of the mRSS even after adjusting for the treatment. Assessment of the best predictive model revealed that patients with a disease duration ≤12 months and mRSS ≤19 had a risk of mRSS worsening within one year, with a sensitivity of 73.9% and specificity of 81.1%. CONCLUSION: Identification of predictors of subsequent worsening of skin thickness in dcSSc patients is useful for identifying patients who require intensive treatment with potential disease-modifying agents and for improving clinical trial design by characterizing eligible progressors in the Japanese population.

Clinical course of Japanese patients with early systemic sclerosis: A multicenter, prospective, observational study.

OBJECTIVES: To investigate the clinical course of Japanese patients with early diffuse cutaneous systemic sclerosis (dcSSc) and early SSc with interstitial lung disease (ILD). METHODS: We prospectively analyzed the clinical features of 207 Japanese patients with early dcSSc (n = 150) and limited cutaneous SSc (lcSSc) with ILD (n = 57) in 10 medical centers every year for 7 consecutive years. RESULTS: Mean modified Rodnan total skin thickness score (mRSS) was 18.3 and 67.4% of the cohort had ILD. Most patients started immunosuppressive therapy and vasodilators during 7 years (83.4% and 87.9%, respectively). Mean value of mRSS of total patients was significantly reduced from the initial registration after the first year. However, other parameters for physical function associated with skin sclerosis including fist closure, hand extension, and oral aperture were not so ameliorated during the study period. Health Assessment Questionnaire-disability index and serum KL-6 levels were constant throughout the course. Percent vital capacity and the presence of ILD, clinically suspected pulmonary arterial hypertension, and digital ulcers were gradually exacerbated during the period. CONCLUSION: In Japanese early dcSSc patients and SSc patients with ILD, mRSS was continuously reduced during 7 years of follow-up, but there was little improvement of physical disability and organ involvement.

Shifting trophic control of fishery-ecosystem dynamics following biological invasions.

Increasing human population size and mobility have accelerated the translocation of nonnative species globally, which has become a major threat to conservation of biodiversity and ecosystem services. Introduced species can disrupt species interactions of the recipient ecosystem, triggering system-wide events, and amplify or dampen effects of existing pressures. We show how two pervasive intercontinental invasive consumers in North American lakes, dreissenids (filter-feeding mussels) and Bythotrephes (carnivorous zooplankton), nonlinearly modify consumer-resource dynamics and undermine management interventions to rebuild cold-water predatory fish biomass. Synthesizing 30 yr (1986-2015) of lake-wide monitoring data with a dynamic mass-balance food-web model (consisting of 61 species and trophic groups), we reconstructed historical food-web dynamics of Lake Simcoe, a large, temperate lake in Ontario, Canada that has shifted from a turbid to clear-water state. We then analyzed patterns of biomass fluctuations of three recreationally harvested, ecologically connected populations; lake trout (Salvelinus namaycush, a piscivore), lake whitefish (Coregonus clupeaformis, a benthivore), and cisco (C. artedi, a planktivore) before and after the invasions by testing hypotheses on their delayed recoveries under management interventions-predator manipulations (fishery removal and stocking) and nutrient (phosphorus) load reduction. Analyses suggest that fishery harvest primarily regulated early recovery trajectories of the piscivore and planktivore, weakening top-down control prior to the establishment of the invasive consumers. By contrast, the benthivore biomass patterns were shaped, in part, by the invasive mussels (via diet shift), independently of management actions. Although improved water quality (with reduced hypoxia in deeper water) and, in turn, higher macrophyte production are projected to expand the predation refuge for young fish, intensified planktivory (by Bythotrephes) and herbivory (by dreissenids) have triggered shifts in community composition (from pelagic to demersal dominance). These system-wide shifts, in turn, have substantially diminished ecosystem productivity, thereby shrinking fishery yields. Novel consumers can rewire food webs, disrupt energy flows, and suppress predator recoveries, underscoring the need to account for altered ecological reality when sustainably managing fishery resources in invaded ecosystems.

Placenta Specific 8 Suppresses IL-18 Production through Regulation of Autophagy and Is Associated with Adult Still Disease.

Adult Still disease (ASD) is a systemic disorder of unknown etiology characterized by high spiking fever, rash, and arthritis. The purpose of this study was to identify genes specifically associated with the active phase of the disease. In this study, we have reported that placenta specific 8 (PLAC8) was a newly specific gene involved in ASD. DNA microarray and validation analysis using human monocytes revealed that the expression of PLAC8 was significantly higher in active-ASD patients than in inactive-ASD patients and healthy controls. In ASD, PLAC8 expression level correlated with serum levels of CRP, ferritin, IL-1ß, and IL-18. Stimulation of monocytes with LPS results in PLAC8 upregulation. LPS or nigericin stimulation of PLAC8-overexpressing human monocytic cell line (THP-1), but not mock THP-1 cells, was associated with a significant decrease in IL-1ß and IL-18 production. PLAC8 overexpression in THP-1 cells was associated with enhanced autophagy and suppression of IL-1ß and IL-18 production. Therefore, we found that PLAC8 was upregulated in activated monocytes, as was IL-1ß and IL-18. The upregulated PLAC8 acts on the synthesis of inactive precursors of IL-1ß and IL-18 and seemed to suppress the production of IL-1ß and IL-18 by negative feedback through enhanced autophagy, resulting in the suppression of ASD. The results highlight the role of PLAC8 in the pathogenesis of ASD and suggest its potential suitability as an activity marker and therapeutic target in ASD.

Opportunities to implement a sustainable genomic medicine program: lessons learned from the IGNITE Network.

PURPOSE: While there is growing scientific evidence for and significant advances in the use of genomic technologies in medicine, there is a significant lag in the clinical adoption and sustainability of genomic medicine. Here we describe the findings from the National Human Genome Research Institute's (NHGRI) Implementing GeNomics In pracTicE (IGNITE) Network in identifying key constructs, opportunities, and challenges associated with driving sustainability of genomic medicine in clinical practice. METHODS: Network members and affiliates were surveyed to identify key drivers associated with implementing and sustaining a genomic medicine program. Tallied results were used to develop and weigh key constructs/drivers required to support sustainability of genomic medicine programs. RESULTS: The top three driver-stakeholder dyads were (1) genomic training for providers, (2) genomic clinical decision support (CDS) tools embedded in the electronic health record (EHR), and (3) third party reimbursement for genomic testing. CONCLUSION: Priorities may differ depending on healthcare systems when comparing the current state of key drivers versus projected needs for supporting genomic medicine sustainability. Thus we provide gap-filling guidance based on IGNITE members' experiences. Although results are limited to findings from the IGNITE network, their implementation, scientific, and clinical experience may be used as a road map by others considering implementing genomic medicine programs.

Movement rule selection through eco-genetic modeling: Application to diurnal vertical movement.

Agent-based, spatially-explicit models that incorporate movement rules are used across ecological disciplines for a variety of applications. However, appropriate movement rules may be difficult to implement due to the complexity of an individual's response to both proximate and ultimate cues, as well as the difficulty in directly assessing how organisms choose to move across their environment. Environmental cues may be complex and dynamic, and therefore, movement responses may require tradeoffs between preferred levels of different environmental variables (e.g., temperature, light level, and prey availability). Here, we present an approach to determine appropriate movement rules by setting them as heritable traits in an eco-genetic modeling framework and allowing movement rules to evolve during the model rather than setting them a priori. We modeled yellow perch, Perca flavescens, movement in a simulated environment and allowed perch to move in response to high-resolution vertical gradients in temperature, dissolved oxygen, light, predators, and prey. Evolving movement rules ultimately increased fish growth and survival over generations in our model, indicating that evolving movement rules led to improved individual performance. We found that emergent movement rules were consistent across trials, with evolved movement rules incorporating different weights of these environmental factors and the most rapid selection on temperature preference. This case study presents a flexible method using eco-genetic modeling to determine appropriate movement rules that can be applied to diverse scenarios in spatially-explicit ecological modeling.

Endoscopic Ultrasound-Guided Rendezvous Technique for Failed Biliary Cannulation in Benign and Resectable Malignant Biliary Disorders.

BACKGROUND: Endoscopic ultrasound-guided rendezvous technique (EUS-RV) has emerged as an effective salvage method for unsuccessful biliary cannulation. However, its application for benign and resectable malignant biliary disorders has not been fully evaluated. AIMS: To assess the efficacy and safety of EUS-RV for benign and resectable malignant biliary disorders. METHODS: This was a multicenter prospective study from 12 Japanese referral centers. Patients who underwent EUS-RV after failed biliary cannulation for biliary disorder were candidates for this study. Inclusion criteria were unsuccessful biliary cannulation for therapeutic endoscopic retrograde cholangiopancreatography with benign and potentially resectable malignant biliary obstruction. Exclusion criteria included unresectable malignant biliary obstruction, inaccessible papillae due to surgically altered upper gastrointestinal anatomy or duodenal stricture, and previous sphincterotomy and/or biliary stent placement. The primary outcome was the technical success rate of biliary cannulation; procedure time, adverse events, and clinical outcomes were secondary outcomes. RESULTS: Twenty patients were prospectively enrolled. The overall technical success rate and median procedure time were 85% and 33 min, respectively. Guidewire manipulation using a 4-Fr tapered tip catheter contributed to the success in advancing the guidewire into the duodenum. Adverse events were identified in 15% patients, including 2 with biliary peritonitis and 1 mild pancreatitis. EUS-RV did not affect surgical maneuvers or complications associated with surgery, or postoperative course. CONCLUSIONS: EUS-RV may be a safe and feasible salvage method for unsuccessful biliary cannulation for benign or resectable malignant biliary disorders. Use of a 4-Fr tapered tip catheter may improve the overall EUS-RV success rate.

Three nights leg thermal therapy could improve sleep quality in patients with chronic heart failure.

Sleep quality is often impaired in patients with chronic heart failure (HF), which may worsen their quality of life and even prognosis. Leg thermal therapy (LTT), topical leg warming, has been shown to improve endothelial function, oxidative stress, and cardiac function in patients with HF. However, its short-term influence to sleep quality has not been evaluated in HF patients. Eighteen of 23 patients with stable HF received LTT (15 min of warming at 45 °C and 30 min of insulation) at bedtime for 3 consecutive nights and 5 patients served as control. Subjective sleep quality was evaluated by St. Mary's Hospital Sleep Questionnaire, Oguri-Shirakawa-Azumi Sleep Inventory, and Epworth sleepiness scale, and also objectively evaluated by polysomnography. LTT significantly improved subjective sleep quality indicated by depth of sleep (p < 0.01), sleep duration (p < 0.05), number of awaking (p < 0.01), nap duration (p < 0.01), sleep quality (p < 0.05), and sleep satisfaction (p < 0.05). It was also objectively affirmed by a slight but significant decrease of sleep stage N1 (p < 0.01), and increase in sleep stage N2 (p < 0.05). No significant changes occurred in the controls. Hence, the short-term LTT could improve subjective and objective sleep quality in patients with HF. LTT can be a complimentary therapy to improve sleep quality in these patients.

Transethnic meta-analysis identifies GSDMA and PRDM1 as susceptibility genes to systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is an autoimmune disease characterised by skin and systemic fibrosis culminating in organ damage. Previous genetic studies including genome-wide association studies (GWAS) have identified 12 susceptibility loci satisfying genome-wide significance. Transethnic meta-analyses have successfully expanded the list of susceptibility genes and deepened biological insights for other autoimmune diseases. METHODS: We performed transethnic meta-analysis of GWAS in the Japanese and European populations, followed by a two-staged replication study comprising a total of 4436 cases and 14 751 controls. Associations between significant single nuclear polymorphisms (SNPs) and neighbouring genes were evaluated. Enrichment analysis of H3K4Me3, a representative histone mark for active promoter was conducted with an expanded list of SSc susceptibility genes. RESULTS: We identified two significant SNP in two loci, GSDMA and PRDM1, both of which are related to immune functions and associated with other autoimmune diseases (p=1.4×10-10 and 6.6×10-10, respectively). GSDMA also showed a significant association with limited cutaneous SSc. We also replicated the associations of previously reported loci including a non-GWAS locus, TNFAIP3. PRDM1 encodes BLIMP1, a transcription factor regulating T-cell proliferation and plasma cell differentiation. The top SNP in GSDMA was a missense variant and correlated with gene expression of neighbouring genes, and this could explain the association in this locus. We found different human leukocyte antigen (HLA) association patterns between the two populations. Enrichment analysis suggested the importance of CD4-naïve primary T cell. CONCLUSIONS: GSDMA and PRDM1 are associated with SSc. These findings provide enhanced insight into the genetic and biological basis of SSc.

Linkage of Lower Urinary Tract Symptoms to Sleep Quality in Elderly Men with Nocturia: A Community Based Study Using Home Measured Electroencephalogram Data.

PURPOSE: We objectively investigated the relationship between sleep quality/efficiency and factors associated with micturition using at-home electroencephalogram assessment. MATERIALS AND METHODS: Participants were recruited from among those enrolled in the Fujiwara-kyo Study, a community based longitudinal evaluation that began in Nara Prefecture, Japan, in 2007. Included participants were men at least 65 years old who woke up in the middle of the night/early morning at least 3 times per week with the urge to void. We evaluated lower urinary tract symptoms using the I-PSS and subjective sleep quality using the Pittsburgh Sleep Quality Index. Uroflowmetry and 3-day frequency volume charting measurements were also obtained. Electroencephalogram recordings were obtained during sleep to evaluate objective sleep quality. RESULTS: Final analysis included data from 47 participants. I-PSS-quality of life score and slow wave sleep time were independent predictors of good subjective sleep quality as determined by Pittsburgh Sleep Quality Index scores. Nocturnal urinary volume was an independent predictor of greater sleep efficiency. Maximum flow rate was an independent predictor of longer slow wave sleep time. CONCLUSIONS: In elderly men with nocturia, sleep quality is associated with lower urinary tract function. Higher subjective sleep quality is associated with longer slow wave sleep time and less severe lower urinary tract symptoms. Higher objective sleep quality is further associated with a higher urinary flow rate and lower nocturnal urinary volume.

Clinical efficacy and safety of mirabegron and imidafenacin in women with overactive bladder: A randomized crossover study (the MICRO study).

AIMS: We aimed to compare the efficacy and safety of mirabegron, a ß3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients. METHODS: We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged ≥50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B. RESULTS: A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not. CONCLUSIONS: Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. © 2016 Wiley Periodicals, Inc.

Functional structure and physiological functions of mammalian wild-type HSP60.

The Chaperonins comprise a family of molecular chaperones having a double-ring structure and similar sequence homology. These proteins play an essential role in biological reactions that mediate the folding of newly synthesized polypeptides and partially denatured proteins. In the prokaryotic group I chaperonins, structural and reaction cycle analyses of GroEL and its co-chaperone GroES have been performed in detail. While in eukaryotes, there have been limited reports analyzing the group I chaperonin HSP60 and its co-chaperone HSP10. In the present study, we purified the wild type HSP60 from porcine liver and investigated the interaction between HSP60 and HSP10, including conformation and physiological relationships. Based on the results of transmission electron microscopy, native PAGE, and gel filtration column chromatography, the wild type HSP60 displayed a heptameric single-ring structure in the absence of ATP. In contrast, HSP60 formed mainly a "football-type" complex with HSP10 in the presence of ATP and mediated the refolding of denatured substrate protein. The functional conformation cycle of the purified mammalian HSP60 is distinct from the cycle of the prokaryotic GroEL/GroES chaperonin.

Correlation between serum cytokeratin-18 and the progression or regression of non-alcoholic fatty liver disease.

BACKGROUND: Diagnosis of non-alcoholic fatty liver disease (NAFLD) is limited by the need for liver biopsies. Serum cytokeratin 18 (CK-18) levels have been investigated as potential biomarkers for the presence of NAFLD and non-alcoholic steatohepatitis (NASH). Herein, we assessed the correlation between CK-18 levels and NAFLD progression. MATERIAL AND METHODS: Serum CK-18 levels were estimated using the M30 antibody enzyme-linked immunosorbent assay in 147 patients diagnosed with NAFLD. In 72 patients, disease progression was evaluated by repeated liver biopsy, which was conducted after 4.3 ± 2.6 years. The relationship between the CK-18 levels and liver histological findings was assessed. RESULTS: The CK-18 levels were useful for identifying NAFLD patients with NAFLD activity scores (NAS) ≥ 5 (NAS ≥ 5 vs. ≤ 4: 675.1 U/L vs. 348.7 U/L; p < 0.0001). A cut-off value of 375 U/L was calculated using the receiver operating characteristic curve approach, with a specificity and sensitivity of 81.5 and 65%, respectively, for the diagnosis of NASH. Among the 72 patients who underwent repeated liver biopsy, 11 patients with a progressed NAS also had significantly increased serum CK-18 levels (p < 0.01); in 30 patients with an improved NAS, there was a significant improvement in the mean CK-18 levels (p < 0.0001). The 31 patients with static NAS had static CK-18 levels. CONCLUSIONS: In conclusion, serum CK-18 levels can predict NAS ≥ 5 in NAFLD patients. In NAFLD patients, serum CK-18 levels reflect NAS values and correlate with histological changes, and they appear to be useful indicators of progression and improvement.

[A case of ruptured duodenal varices successfully treated by combination therapy with endoscopic clipping and balloon-occluded retrograde transvenous obliteration].

An 80-year-old woman with a history of chronic hepatitis B was referred to our hospital because of upper gastrointestinal bleeding of unknown origin. Dynamic computed tomography revealed liver cirrhosis and hepatofugal collateral vessels around the duodenum. Emergency esophagogastroduodenoscopy showed duodenal varices with an erosive spot, highly suggestive of a variceal rupture site. We immediately performed endoscopic clipping of the ruptured site to achieve temporary hemostasis. Ten days later, elective balloon-occluded retrograde transvenous obliteration (B-RTO) was performed to prevent recurrence. We describe a successfully treated case of duodenal variceal rupture managed by combination therapy with endoscopic clipping and B-RTO.

Involvement of CD161+ Vδ1+ γδ T cells in systemic sclerosis: association with interstitial pneumonia.

OBJECTIVE: Interstitial pneumonia (IP) is a chronic progressive interstitial lung disease associated with high mortality and poor prognosis. However, the pathogenesis of IP remains to be elucidated. The aim of this study was to clarify the role of CD161(+) Vδ1(+) γδ T cells in SSc patients with IP. METHODS: The proportion of CD161(+) Vδ1(+) γδ T cells in peripheral blood mononuclear cells (PBMCs) and serum sialylated carbohydrate antigen (KL-6) levels were determined. GeneChip analysis was performed with CD161(-) and CD161(+) Vδ1(+) γδ T cells. Cytokine and chemokine expression from CD161(+) Vδ1(+) γδ T cells was measured and used to evaluate the effect of culture supernatant on fibroblast proliferation. RESULTS: The proportion of CD161(+) Vδ1(+) γδ T cells was significantly higher in SSc than healthy controls (HCs) and correlated negatively with serum KL-6 levels in IP-positive SSc patients. The gene and mRNA expression level of chemokine ligand 3 (CCL3) was markedly higher in CD161(+) Vδ1(+) γδ T cells than in CD161(-) Vδ1(+) γδ T cells. CD161(+) Vδ1(+) γδ T cells in IP-positive SSc patients showed higher production of CCL3 and lower production of IFN-γ than in HCs. Culture supernatant derived from IP-negative and IP-positive SSc patients promoted fibroblast proliferation, whereas that from HCs did not. CONCLUSION: The small proportion and the altered cell functions of CD161(+) Vδ1(+) γδ T cells among PBMCs in SSc patients play a role in the pathogenesis of IP. These findings suggest that CD161(+) Vδ1(+) γδ T cells may play a regulatory role in the pathogenesis of IP in SSc patients via IFN-γ production.