Non-cardiac comorbid health outcomes and prevalence after myocardial infarction: an umbrella review.

OBJECTIVE: There exists limited comprehensive evidence on the potential association between non-cardiac comorbidities and myocardial infarction (MI). Thus, we conducted an umbrella review of existing meta-analyses to provide a broad understanding of non-cardiac health outcomes associated with MI. MATERIALS AND METHODS: The primary focus on the prevalence of related health outcomes in patients with MI was systemically searched. Each original meta-analysis that was included had its methodological quality evaluated by a Measurement Tool Assessment Systematic Reviews 2 (AMSTAR2). To evaluate the certainty in the evidence for each outcome, we employed GRADE and the Joanna Briggs Institute Prevalence Critical Appraisal Tool. The protocol was registered in PROSPERO (CRD42023458642). RESULTS: We identified seven meta-analyses comprising 126 studies with 336,581 participants from 22 countries and five continents. The pooled prevalence of comorbidities in patients with MI was 39% anxiety [95% confidence interval (CI), 30-48; GRADE, very low certainty], 29% depression (95% CI, 23-36; very low certainty), 39% frailty (95% CI, 24-55; very low certainty), and 23% failure of returning to work (95% CI, 16-29; very low certainty). The diagnosis of MI was associated with an increased risk of cognitive impairment (odds ratio, 1.45; 95% CI, 1.10-1.92; moderate certainty). Among frail patients, MI was associated with an increased risk of major bleeding (relative risk, 1.93; 95% CI, 1.08-3.45; low certainty) and mortality (relative risk, 2.29; 95% CI, 1.48-3.53; moderate certainty). However, we did not find any evidence of cancer risk associated with the development of MI. CONCLUSIONS: Our umbrella meta-analysis provided comprehensive evidence of the association between MI and several non-cardiac health conditions. The robustness of our study is attributed to the integration of evidence across several studies, thus, these insights offer valuable treatment options for policymakers and physicians to develop personalized health strategies.

Retroductal Delivery of Epidermal Growth Factor Protects Salivary Progenitors after Irradiation.

Salivary gland hypofunction after irradiation is associated with a deficit of epithelial stem/progenitors in salivary glands. Although epidermal growth factor (EGF) is known to stimulate the proliferation of epithelial cells, the therapeutic effect of EGF on salivary epithelial stem/progenitors remains undetermined. In this study, we administered EGF to submandibular glands (SMGs) via a retrograde route through the SMG excretory duct before fractionated irradiation and examined whether EGF could protect salivary epithelial progenitor cells from radiation and alleviate radiation-induced salivary hypofunction. EGF-treated mice exhibited greater body and gland weights at 12 wk after irradiation than untreated mice. The retroductal delivery of EGF improved salivary secretory function and increased salivary amylase activity in a dose-dependent manner. Histological examinations highlighted the amelioration of the loss of keratine-14+ (KRT14+) basal ductal and/or MIST1+ acinar cells, as well as induction of fibrosis, following irradiation in EGF-treated mice. An additional in vitro experiment using a salivary gland organoid irradiation model indicated that the radioprotective effects of EGF promoted the growth and inhibited the apoptotic cell death of salivary epithelial cells. Our results suggest that retroductal delivery of EGF may be a promising therapeutic option for preventing radiation-induced salivary gland hypofunction.

Prevalence and treatment of new-onset diabetes mellitus after liver transplantation in Korean children: a single-center study.

The aim of this study was to investigate the prevalence, clinical characteristics, and management of new-onset diabetes mellitus (NODM) in Korean children with liver transplantation (LT). We retrospectively analyzed the medical records of 200 pediatric patients (5 months to 17 years old) who underwent LT at Asan Medical Center between January 1994 and December 2010; 26 pediatric patients who died at the maximal follow-up after LT or who were lost to follow-up were excluded from the study. Among these 174 children, NODM after LT developed in 18. The median interval time at the presentation of NODM after LT was 15 days (range, 1 day to 16.0 years), whereas the median patient age of NODM diagnosis was 10 years (range, 1.1 to 17.0 years). Insulin treatment with reduction in tacrolimus dosage, steroid tapering, and conversion from tacrolimus to cyclosporine with or without mycophenolate mofetil is highly effective in NODM after LT. In conclusion, careful diabetes mellitus monitoring and modification of immunosuppressive regimen should be required in pediatric patients after LT.

Comparison of alfuzosin 10 mg with or without propiverine 10 mg, 20 mg in men with lower urinary tract symptom and an overactive bladder: randomised, single-blind, prospective study.

PURPOSE: The efficacy and safety of treatment with alfuzosin 10 mg plus propiverine 10 or 20 mg in men with lower urinary tract symptoms (LUTS) and an overactive bladder were investigated. MATERIALS AND METHODS: In this parallel-arm, prospective, multicentre, single-blind study, men who were ≥ 40 years old, had an International Prostate Symptom Score (IPSS) of ≥ 8, an Overactive Bladder Symptom Score (OABSS) of ≥ 3 and an OABSS urgency item score of ≥ 2 were randomised in a 1 : 1 :1 ratio to receive alfuzosin 10 mg alone (Group A) or with propiverine 10 mg (Group B) or 20 mg (Group C) for 8 weeks. Four and 8 weeks after commencing treatment, OABSS was measured along with IPSS, maximal urinary flow rate (Qmax ) and postvoid residual volume (PVR). Adverse events were recorded. RESULTS: A total of 135 men, including 43 in Group A, 48 in Group B and 44 in Group C, completed the study. Relative to baseline, all groups demonstrated significant reductions in OABSS and the IPSS after eight treatment weeks (p < 0.005). The improvement of OABSS in Group C was significantly greater than Group A and B (Group A: 0.70 ± 1.94; Group B: 2.50 ± 2.98; Group C: 4.30 ± 3.40; p < 0.005). An observed improvement of Qmax and PVR in the three groups did not achieve statistical significance. Overall adverse event rates were higher in Group C but not significant compared with others. CONCLUSION: In patients with LUTS and overactive bladder, combined therapy with alfuzosin 10 mg plus propiverine 20 mg was significantly more effective than alfuzosin monotherapy and propiverine 10 mg combined therapy in terms of improving OABSS while not significantly affecting Qmax or PVR.

Comparison of efficacy for erectile function and lower urinary tract symptoms of tadalafil 20 mg on-demand and 5 mg once daily in patients with erectile dysfunction.

Aim: To compare the improvement in erectile dysfunction (ED) and lower urinary tract symptoms (LUTS) as well as safety of tadalafil dosed at 20 mg on-demand and 5 mg once daily among ED patients. Materials and methods: A total of 194 ED patients visited between March 2010 and June 2011 were recruited. Out of 194 individuals, 168 (86.6%) met inclusion criteria after completing the two-week screening period (V0). The Patients were randomly allocated into two groups: (i) 20 mg of tadalafil as needed (Group 1: n = 84, 50.0%) and (ii) 5 mg of tadalafil once daily (Group 2: n = 84, 50.0%). Blood pressure (BP), heart rate (HR) and the five-item version of the International Index of Erectile Function (IIEF-5) were assessed immediately before initiation of treatment (V1) and after four (V2) and twelve weeks of treatment (V3). In men with an IPSS of ≥ 8 at V1, IPSS, maximal flow rate (Qmax) and post-void residual volume (PVR) were also assessed. Results: Of the 168 patients, 134 (79.8%; Group 1: n = 68, 81.0%; Group 2: n = 66, 78.6%) patients completed the trial. IIEF-5 improved in both groups, and the mean change was larger in Group 2 at V3 (4.9 ± 4.2 vs. 6.5 ± 4.5; p = 0.032) Similarly, though IPSS (with ≥ 8, n = 88, 65.7%; Group 1: n = 44, 64.7%; Group 2: n = 44, 66.7%) improved in both groups, the mean change was larger in Group 2 at V3 (-2.8 ± 4.3 vs. -4.8 ± 4.1; p = 0.026). Qmax and PVR did not differ significantly in either group. Conclusions: Once daily tadalafil was more efficacious in treating both ED and LUTS than on-demand dosing. However, no differences were observed between the two dosing schedules with regard to the improvement in LUTS when stratified by improvement in ED. The side effects were insignificant for both dosing schedules.

Contrast-enhanced MR cholangiography: comparison of Gd-EOB-DTPA and Mn-DPDP in healthy volunteers.

OBJECTIVE: The purpose of this study was to compare the biliary enhancement dynamics of gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic-acid (Gd-EOB-DTPA) and mangafodipir trisodium (Mn-DPDP) for contrast-enhanced MR cholangiography (MRC) in healthy subjects. METHODS: 15 healthy volunteers underwent MRI at 1.5 T with volumetric interpolated breath-hold examination sequence. Each volunteer was scanned once for each contrast agent. The signal-to-noise ratio (SNR) of the liver parenchyma and common hepatic duct (CHD) and the contrast-to-noise ratio (CNR) of CHD to liver parenchyma were evaluated and compared before and at several time points (5, 15, 30, 45, 60, 90, and 120 min) after injection of each agent. RESULTS: SNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP in liver parenchyma after 5 min and in CHD after 15 min (p<0.05). CNR of CHD to liver parenchyma using Gd-EOB-DTPA showed an initial decrease at 5 min post-injection followed by a steep increase to a peak at 15 min post-injection. CNR using Mn-DPDP showed a steady increase to a peak at 15 min post-injection without an initial decrease. At 15 min, the value of CNR was significantly higher for Gd-EOB-DTPA than for Mn-DPDP (p<0.05). CONCLUSION: For both contrast agents, CNR reached a peak at 15 min after contrast injection. At this time point, CNR of Gd-EOB-DTPA was significantly higher than that of Mn-DPDP. Therefore, Gd-EOB-DTPA may provide better contrast-enhanced MRC than Mn-DPDP at 15 min after contrast administration.

De novo autoimmune hepatitis in Korean children after liver transplantation: a single institution's experience.

INTRODUCTION: De novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) has been described as a new type of late graft dysfunction in children who have not undergone transplantation for previous autoimmune liver disease. The purpose of this study was to evaluate the clinical aspects of de novo AIH among children following OLT. PATIENTS AND METHODS: Between January 1994 and May 2007, 149 children underwent OLT, including 1 with recurrent AIH who was excluded from this study, whereas 4 others developed de novo AIH (2.7%; n = 4/148). We analyzed the demographics, laboratory characteristics, and response to treatment of the 4 children with de novo AIH following OLT. RESULTS: The 4 patients were all girls with a median interval after OLT to presentation of 6.5 years (range, 0.7-8.8 years). The median age when de novo AIH developed was 12.4 years (range, 8.7-17.3 years). All cases were detected by abnormal liver function tests, namely, increased aspartate aminotransferase (AST; median, 322 IU/L; range, 181-919 IU/L). One patient showed elevated immunoglobulin G. Three patients displayed positive antinuclear antibodies. All were seronegative for smooth muscle antibody and liver-kidney microsomal type 1 antibody. One patient showed anti-mitochondrial antibody. All patients were treated with steroids with or without azathioprine. The liver function tests in these 4 patients, improved by at least 50% during the first month of treatment, responding to steroid treatment with or without azathioprine. CONCLUSION: In preadolescent or adolescent female patients with unexplained graft dysfunction after OLT, it is important to recognize de novo AIH rapidly and to develop an adequate diagnostic strategy, including evaluation of serum autoantibodies, immunoglobulin G, and liver biopsy.

Overexpression of SERTAD3, a putative oncogene located within the 19q13 amplicon, induces E2F activity and promotes tumor growth.

The amplified region of chromosome 19q13.1-13.2 has been associated with several cancers. The well-characterized oncogene AKT2 is located in this amplicon. Two members of the same gene family (SERTAD1 and SERTAD3) are also located within this region. We report herein the genomic structure and potential functions of SERTAD3. SERTAD3 has two transcript variants with short mRNA half-lives, and one of the variants is tightly regulated throughout G1 and S phases of the cell cycle. Overexpression of SERTAD3 induces cell transformation in vitro and tumor formation in mice, whereas inhibition of SERTAD3 by small interfering RNA (siRNA) results in a reduction in cell growth rate. Furthermore, luciferase assays based on E2F-1 binding indicate that SERTAD3 increases the activity of E2F, which is reduced by inhibition of SERTAD3 by siRNA. Together, our data support that SERTAD3 contributes to oncogenesis, at least in part, via an E2F-dependent mechanism.

Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development.

Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.

A diagnosis system for the spinal column nerve damaged patients.

Visible evidence of spinal column damage is only apparent in 14% of the patients who receive spinal damage. We use a humidity sensor array. The humidity sensor (HDP-05) is arranged and attached to pre-assigned regions along the spinal column nerve of the actual patient. Applying pressure to the urinary bladder causes the patient to sweat. It is possible to determine which spinal column autonomic nerve is damaged in a region by humidity value. But also have some problem is that sometimes the damaged region has same value as a normal region. If will find a better attachment method and a more sensitive sensor could be found the results will be better and more precise.

Preliminary study for gait phases detection to develop a rehabilitation equipment for hemiplegic patients.

Preliminary experiment for analyzing weight shift during gait phases for hemiplegic patients was carried out to develop rehabilitation equipment. A gait phase detection system using pressure sensors was developed and the experiment was carried out for eight hemiplegic patients and normal adult. The weight shift during gait phases for a normal adult showed symmetrical for left and right footing phase, but that for the hemiplegic patients showed asymmetrical footing phase. However, it gave sufficient information to discriminate between left and right footing phases.

Detection of hepatocellular carcinoma: combined T2-weighted and dynamic gadolinium-enhanced MRI versus combined CT during arterial portography and CT hepatic arteriography.

PURPOSE: The purpose of this study was to compare the preoperative detectability of hepatocellular carcinomas (HCCs) using combined T2-weighted and dynamic gadolinium-enhanced MRI and combined CT during arterial portography (CTAP) and CT hepatic arteriography (CTHA). METHOD: Thirty-three patients with 43 HCCs underwent T2-weighted and dynamic gadolinium-enhanced MRI and combined CTAP and CTHA. The diagnosis was established by pathologic examination following surgical resection in 26 patients and by biopsy in 7 patients. The MR protocol included fast SE with two TEs (including T2-weighted imaging) and precontrast and gadolinium-enhanced T1-weighted fast multiplanar spoiled gradient-recalled echo images with dynamic study. The MR images of all sequences and the paired CTAP and CTHA images were independently reviewed by three radiologists. Image review was conducted on a segment-by-segment basis. Diagnostic accuracy was evaluated with receiver operating characteristic analysis. RESULTS: The accuracies (Az values) of MRI of all sequences and combined CTAP and CTHA for all observers were 0.960 and 0.959, respectively. The mean sensitivities of MRI and CT were 90 and 94%, respectively. The differences were not statistically significant. The mean specificity of MRI (99%) was significantly higher than that of combined CTAP and CTHA (92%). CONCLUSION: Combined T2-weighted and dynamic gadolinium-enhanced MRI is as accurate as combined CTAP and CTHA for preoperative detection of HCCs.

Folding and stability of sweet protein single-chain monellin. An insight to protein engineering.

Engineered single-chain monellin (SCM) proteins were constructed by recombinant technology without disrupting the topology and sweet activity of native protein. Data from 8-anilinonaphthalene-1-sulfonic acid fluorescence, size-exclusion chromatography, and heteronuclear NMR strongly suggest the presence of a folding intermediate at 1.5 m GdnHCl for SCM protein. The structural feature of the folding intermediate from NMR data reveals that the secondary structures became mostly unstable, and protein experiences a dynamic equilibrium between native and unfolded state. All backbone amide protons exchange within 10 min, which imply that no stable hydrogen bonds exist in the secondary structural regions in the folding intermediate. From equilibrium unfolding and mutagenesis studies, the unfolding transition midpoints of mutant proteins gradually shifted toward lower denaturant concentration, indicating stability reductions of mutant proteins. Our results suggest that stability and folding pathways of SCM proteins could be regulated by a combined study of spectroscopy and mutagenesis, and these studies will provide useful information for understanding the folding kinetics of novel engineered proteins.

Non-combustible waste vitrification with plasma torch melter.

Non-combustible radioactive wastes generated from Nuclear Power Plants (NPPs) are composed of concrete, glass, asbestos, metal, sand, soil, spent filters, etc. The melting tests for concrete, glass, sand, and spent filters were carried out using a 60 kW plasma torch system. The surrogate wastes were prepared for the tests. Non-radioactive Co and Cs were added to the surrogates in order to simulate the radioactive waste. Several kinds of surrogate prepared by their own mixture or by single waste were melted with the plasma torch system to produce glassy waste forms. The characteristics of glassy waste forms were examined for the volume reduction factor (VRF) and the leach rate. The VRFs were estimated through the density measurement of the surrogates and the glassy waste forms, and were turned out to be 1.2-2.4. The EPA (Environmental Protection Agency) Toxicity Characteristic Leaching Procedure (TCLP) was used to determine the leach resistance for As, Ba, Hg, Pb, Cd, Cr, Se, Co, and Cs. The leaching index was calculated using the total content of each element in both the waste forms and the leachant. The TCLP tests resulted in that the leach rates for all elements except Co and Cs were lower than those of the Universal Treatment Standard (UTS) limits. There were no UTS limits for Co and Cs, and their leach rate & index from the experiments were resulted in around 10 times higher than those of other elements.

Experimental and modeling evaluation of upward and downward velocities in the coaxial flotation column.

This study was conducted to show the influence of upward velocity in the inner column and downward velocity in the outer column of the coaxial cylinder-type flotation column on the solids removal efficiency, solids concentration in the treated water, and so on. The SIMPLE (Semi-Implicit Method for Pressure Linked Equation) solution was applied to the coaxial flotation column to simulate the velocity vectors of the elements of water flowing in the column. The effects of solids loading and residence time in the agglomerate separation zone on the solids removal efficiency were also tested. In the pilot scale coaxial DAF column experiments with solids concentration of 1,000-2,000 mg of SS per liter and solids loading less than 350 kg/m2/day, approximately 90% of the solids removal efficiencies were obtained using the upward velocity of up to 110 cm/min in the contact zone of the inner column and the downward velocity of up to 30 cm/min in the outer column. In the simulation, similar results were observed as in the experiments. The solids loading in the excess of 350 kg/m2/day caused the instability of the sludge float layer and aggravated the quality of the treated water.

Solution structure, backbone dynamics, and stability of a double mutant single-chain monellin. structural origin of sweetness.

Single-chain monellin (SCM), which is an engineered 94-residue polypeptide, has been characterized as being as sweet as native two-chain monellin. Data from gel-filtration high performance liquid chromatography and NMR has proven that SCM exists as a monomer in aqueous solution. In order to determine the structural origin of the taste of sweetness, we engineered several mutant SCM proteins by mutating Glu(2), Asp(7), and Arg(39) residues, which are responsible for sweetness. In this study, we present the solution structure, backbone dynamics, and stability of mutant SCM proteins using circular dichroism, fluorescence, and NMR spectroscopy. Based on the NMR data, a stable alpha-helix and five-stranded antiparallel beta-sheet were identified for double mutant SCM. Strands beta1 and beta2 are connected by a small bulge, and the disruption of the first beta-strand were observed with SCM(DR) comprising residues of Ile(38)-Cys(41). The dynamical and folding characteristics from circular dichroism, fluorescence, and backbone dynamics studies revealed that both wild type and mutant proteins showed distinct dynamical as well as stability differences, suggesting the important role of mutated residues in the sweet taste of SCM. Our results will provide an insight into the structural origin of sweet taste as well as the mutational effect in the stability of the engineered sweet protein SCM.

Expression and purification of an active, full-length hepatitis C viral NS4A.

The nonstructural protein 3 (NS3) of the hepatitis C virus (HCV) is a bifunctional protein with protease and helicase activities. Nonstructural protein 4A (NS4A) is preceded by NS3 and augments the proteolytic activity of NS3 through protein-protein interaction. The central domain of NS4A has been shown to be sufficient for the enhancement of the NS3 protease activity. However, investigations on the roles of the N-terminal and the C-terminal regions of NS4A have been hampered by the difficulty of purification of full-length NS4A, a polypeptide that contains highly hydrophobic amino acid residues. Here we report a procedure by which one can produce and purify an active, full-length NS4A using maltose-binding protein fusion method. The full-length NS4A fused to the maltose binding protein is soluble and maintains its NS3 protease-enhancing activity.

RBT1, a novel transcriptional co-activator, binds the second subunit of replication protein A.

Replication Protein A (RPA) is required for DNA recombination, repair and replication in all eukaryotes. RPA participation in these pathways is mediated by single-stranded DNA binding and protein interactions. We herein identify a novel protein, Replication Protein Binding Trans-Activator (RBT1), in a yeast two-hybrid assay employing the second subunit of human RPA (RPA32) as bait. RBT1-RPA32 binding was confirmed by glutathione S:-transferase pull-down and co-immunoprecipitation. Fluorescence microscopy indicates that green fluorescence protein-tagged RBT1 is localized to the nucleus in vivo. RBT1 mRNA expression, determined by semi-quantitative RT-PCR, is significantly higher in cancer cell lines MCF-7, ZR-75, SaOS-2 and H661, compared to the cell lines normal non-immortalized human mammary epithelial cells and normal non-immortalized human bronchial epithelial cells. Further, yeast and mammalian one-hybrid analysis shows that RBT1 is a strong transcriptional co-activator. Interestingly, mammalian transactivation data is indicative of significant variance between cell lines; the GAL4-RBT1 fusion protein has significantly higher transcriptional activity in human cancer cells compared to human normal primary non-immortalized epithelial cells. We propose that RBT1 is a novel transcriptional co-activator that interacts with RPA, and has significantly higher activity in transformed cells.

Needle-tract implantation in hepatocellular carcinoma: frequency and CT findings after biopsy with a 19.5-gauge automated biopsy gun.

BACKGROUND: Needle-tract implantation is an important complication of cutting biopsy of hepatocellular carcinoma (HCC). This study was performed to evaluate the frequency of needle-tract implantation after ultrasound (US)-guided percutaneous biopsy of HCC and to describe triple-phase helical computed tomographic (CT) findings of implanted nodules. METHODS: Between April 1994 and December 1997, 205 patients underwent US-guided percutaneous biopsy for HCC. Review of medical records and the pathology database disclosed seven patients who were found to have needle-tract implantation of HCC. Among these patients, five underwent triple-phase helical CT examination. We analyzed the frequency of needle-tract implantation and triple-phase helical CT findings of implanted nodules, with particular attention to the morphology and enhancement pattern. RESULTS: Seven of 205 patients (3.4%) had tumor implantation along the needle tract at histologic examination after surgical resection. Eight implanted nodules in five patients were found on triple-phase helical CT images (one nodule in three patients, two nodules in one patient, and three nodules in one patient). All implanted nodules has well-circumscribed margins and were ovoid or lobulated in contour. On triple-phase helical CT, six (75%) implanted nodules were isodense compared with abdominal wall muscle on all triple-phase CTs, and two (25%) nodules were hyperdense on hepatic arterial and portal venous phases and isodense on equilibrium phase. CONCLUSIONS: The frequency of needle-tract implantation of HCC after percutaneous needle biopsy was higher than reported previously, and careful attention should be paid during interpretation of CT images in patients with a history of previous percutaneous biopsy.