ABSTRACT
Laetiporus cremeiporus is the edible mushroom distributed in East Asia. It has been reported that an extract of L. cremeiporus exhibited DPPH radical scavenging activity. The aim of this study is to identify the antioxidant compound from L. cremeiporus. Guided by DPPH radical scavenging activity, a new antioxidant phenolic compound inaoside A (1) and three well-known bioactive compounds 5'-S-methyl-5'-thioadenosine (MTA, 2), nicotinamide (3), and adenosine (4) were isolated from L. cremeiporus. An antioxidant compound was isolated from L. cremeiporus for the first time. This is the first report of the isolation of 1, 2, and 4 from L. cremeiporus. The structures were determined by one- and two-dimensional NMR spectroscopic analysis and chemical derivatization. The antioxidant activities of extracts, fractions, and isolated compounds were evaluated by a DPPH radical scavenging assay. Compound 1 exhibited significant DPPH radical scavenging activity (80 % inhibition at 100 µg/mL, IC50 79.9 µM, trolox equivalent antioxidant capacity (TEAC) = 0.36).
ABSTRACT
Liver cancer, particularly hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC), is more common in Asians than in Caucasians. This is due, at least in part, to regional differences in the prevalence of exogenous factors such as HBV; however, endogenous factors specific to Asia might also play a role. Such endogenous factors include HLA (human leukocyte antigen) genes, which are considered candidates due to their high racial diversity. Here, we performed a pancancer association analysis of 147 alleles of HLA-class I/II genes (HLA-A, B, and C/DRB1, DQA1, DQB1, DPA1, and DPB1) in 31,727 cases of 12 cancer types, including 1684 liver cancer cases and 107,103 controls. HLA alleles comprising a haplotype prevalent in Asia were significantly associated with pancancer risk (e.g., odds ratio [OR] for a DRB1*15:02 allele = 1.12, P = 2.7 × 10-15), and the associations were particularly strong in HBV-related HCC (OR 1.95, P = 2.8 × 10-5). In silico prediction suggested that the DRB1*15:02 molecule encoded by the haplotype does not bind efficiently to HBV-derived peptides. RNA sequencing indicated that HBV-related HCC in carriers of the haplotype shows low infiltration by NK cells. These results indicate that the Asian-prevalent HLA haplotype increases the risk of HBV-related liver cancer risk by attenuating immune activity against HBV infection, and by reducing NK cell infiltration into the tumor.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , Virus Diseases , Humans , Carcinoma, Hepatocellular/genetics , Haplotypes , Hepatitis B virus/genetics , Asian , Gene Frequency , Liver Neoplasms/genetics , Hepatitis B/complications , Hepatitis B/genetics , Virus Diseases/genetics , Alleles , HLA-DRB1 Chains/genetics , Genetic Predisposition to DiseaseABSTRACT
OBJECTIVES: Machine learning-based prediction of hospital admissions may have the potential to optimize patient disposition and improve clinical outcomes by minimizing both undertriage and overtriage in crowded emergency care. We developed and validated the predictive abilities of machine learning-based predictions of hospital admissions in a pediatric emergency care center. METHODS: A prognostic study was performed using retrospectively collected data of children younger than 16 years who visited a single pediatric emergency care center in Osaka, Japan, between August 1, 2016, and October 15, 2019. Generally, the center treated walk-in children and did not treat trauma injuries. The main outcome was hospital admission as determined by the physician. The 83 potential predictors available at presentation were selected from the following categories: demographic characteristics, triage level, physiological parameters, and symptoms. To identify predictive abilities for hospital admission, maximize the area under the precision-recall curve, and address imbalanced outcome classes, we developed the following models for the preperiod training cohort (67% of the samples) and also used them in the 1-year postperiod validation cohort (33% of the samples): (1) logistic regression, (2) support vector machine, (3) random forest, and (4) extreme gradient boosting. RESULTS: Among 88,283 children who were enrolled, the median age was 3.9 years, with 47,931 (54.3%) boys and 1985 (2.2%) requiring hospital admission. Among the models, extreme gradient boosting achieved the highest predictive abilities (eg, area under the precision-recall curve, 0.26; 95% confidence interval, 0.25-0.27; area under the receiver operating characteristic curve, 0.86; 95% confidence interval, 0.84-0.88; sensitivity, 0.77; and specificity, 0.82). With an optimal threshold, the positive and negative likelihood ratios were 4.22, and 0.28, respectively. CONCLUSIONS: Machine learning-based prediction of hospital admissions may support physicians' decision-making for hospital admissions. However, further improvements are required before implementing these models in real clinical settings.
Subject(s)
Hospitalization , Triage , Male , Humans , Child , Child, Preschool , Female , Retrospective Studies , Machine Learning , HospitalsABSTRACT
O-Methyltransferases (OMTs) play important roles in antitumor lignan biosynthesis. To date, six OMTs catalyzing the methylation of dibenzylbutyrolactone lignans as biosynthetic precursors of antitumor lignans have been identified. However, there is still no systematic understanding of the diversity and regularity of the biosynthetic mechanisms among various plant lineages. Herein, we report the characterization of two OMTs from Anthriscus sylvestris and Thujopsis dolabrata var. hondae [designated as AsSecoNorYatein (SNY) OMT and TdSNYOMT] together with the six known OMTs to evaluate their diversity and regularity. Although A. sylvestris 5-O-methylthujaplicatin (SecoNorYatein) and 4-O-demethylyatein (NorYatein) OMT (AsSNYOMT) and TdSNYOMT accept 5-O-methylthujaplicatin and 4-O-demethylyatein as substrates, phylogenetic analysis indicated that these two OMTs shared low amino acid sequence identity, 33.8%, indicating a signature of parallel evolution. The OMTs and the six previously identified OMTs were found to be diverse in terms of their substrate specificity, regioselectivity and amino acid sequence identity, indicating independent evolution in each plant species. Meanwhile, two-entropy analysis detected four amino acid residues as being specifically acquired by dibenzylbutyrolactone lignan OMTs. Site-directed mutation of AsSNYOMT indicated that two of them contributed specifically to 5-O-methylthujaplicatin methylation. The results provide a new example of parallel evolution and the diversity and regularity of OMTs in plant secondary (specialized) metabolism.
Subject(s)
Lignans , Methyltransferases , Animals , Cattle , Methyltransferases/metabolism , Petroselinum/metabolism , Phylogeny , Methylation , Substrate SpecificityABSTRACT
BACKGROUND: Lenvatinib is appropriate for reducing the production of nitric oxide (NO) and facilitating as block angiogenesis. However, to our knowledge, there are no data that support the correlation between NO and clinical response in patients who received lenvatinib therapy for HCC. Therefore, we investigated the correlation between the change rate of NO levels and clinical responses including adverse events (AEs) after lenvatinib therapy for unresectable hepatocellular carcinoma (HCC). METHODS: This study was conducted using previously collected data from another study. We enrolled 70 patients who received lenvatinib for advanced or unresectable HCC. NO was measured by converting nitrate (NO3-) to nitrite (NO2-) with nitrate reductase, followed by quantitation of NO2- based on Griess reagent. To determine whether lenvatinib influences NO in unresectable HCC, we evaluated the influence of the change rate of NO from baseline after administration of lenvatinib on maximal therapeutic response and SAE. RESULTS: After lenvatinib administration, a change rate in the NO from 0.27 to 4.16 was observed. There was no difference between the clinical response to lenvatinib and the change rate of NO (p = 0.632). However, the change rate of NO was significantly lower in patients with AEs than in those without AEs (p = 0.030). When a reduction in NO rate of < 0.8 was defined as a clinically significant reduction of NO (CSRN), the CSRN group had significantly worse progression-free survival (PFS) and overall survival (OS) than the non-CSRN group (p = 0.029 and p = 0.005, respectively). CONCLUSION: Decreased NO levels were associated with the occurrence of AEs and worse prognosis after lenvatinib administration. Change rate in serum NO can be used as predictive markers in patients receiving lenvatinib therapy for HCC.
Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Quinolines , Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/pathology , Humans , Liver Neoplasms/pathology , Nitric Oxide , Nitrogen Dioxide/therapeutic use , Phenylurea Compounds/adverse effects , Quinolines/adverse effectsABSTRACT
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of malignancies that originate from the diffuse neuroendocrine cell system of the pancreas and gastrointestinal tract and have increasingly increased in number over the decades. GEP-NENs are roughly classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas; it is essential to understand the pathological classification according to the mitotic count and Ki67 proliferation index. In addition, with the advent of molecular-targeted drugs and somatostatin analogs and advances in endoscopic and surgical treatments, the multidisciplinary treatment of GEP-NENs has made great progress. In the management of GEP-NENs, accurate diagnosis is key for the proper selection among these diversified treatment methods. The evaluation of hormone-producing ability, diagnostic imaging, and histological diagnosis is central. Advances in the study of the genetic landscape have led to deeper understanding of tumor biology; it has also become possible to identify druggable mutations and predict therapeutic effects. Liquid biopsy, based on blood mRNA expression for GEP-NENs, has been developed, and is useful not only for early detection but also for assessing minimal residual disease after surgery and prediction of therapeutic effects. This review outlines the updates and future prospects of the epidemiology, diagnosis, and management of GEP-NENs.
ABSTRACT
We assessed whether prospective therapeutic drug monitoring to optimise the therapeutic range could prevent linezolid-induced thrombocytopenia. This prospective interventional study was conducted from September 2017 to October 2020 among 37 adult patients receiving linezolid. Patients were administered one of the following two initial dosages: 600 mg twice or once daily for patients with a creatinine clearance rate of ≥50 or <50 mL/min, respectively. Linezolid dosage adjustment was performed on days 3-5 based on the trough concentration. The serum linezolid levels in 22 and 15 patients were within and above the therapeutic range (2-7 µg/mL), respectively. The incidence of thrombocytopenia was significantly lower among patients whose linezolid levels were within the therapeutic range (4.5%;1/22) than in those whose levels were above the therapeutic range (80%; 12/15). It is important to maintain the linezolid level within the therapeutic range at the first therapeutic drug monitoring to prevent thrombocytopenia.
Subject(s)
Anti-Bacterial Agents , Thrombocytopenia , Adult , Anti-Bacterial Agents/adverse effects , Drug Monitoring , Humans , Linezolid/adverse effects , Retrospective Studies , Thrombocytopenia/chemically induced , Thrombocytopenia/prevention & controlABSTRACT
BACKGROUND: Taking advantage of the current advances in diagnostic imaging modalities, including endoscopic ultrasonography (EUS), and due to the increased attention to ectopic fat accumulation in the pancreas following the rising trend of metabolic syndrome, we qualitatively assessed the clinical implication of pancreatic steatosis by EUS in this study. METHODS: The study included 243 patients that were divided into four groups. The correlation between the average echogenicity of the pancreas and that of the control organs and the key clinical data of all study patients were collectively analyzed. The cut-off point of the pancreas-control (PC) ratio in EUS and liver-control (LC) ratio on abdominal ultrasound were determined from the population distribution and the obtained median values. RESULTS: With the cut-off point of 1.30 for the PC ratio and 1.20 for the LC ratio, sex, the Brinkman index, habitual alcohol drinkers, and fatty pancreas were significant factors. The associations between each relevant factor in fatty pancreas, metabolic syndrome in the fatty liver group, and age in the pancreatic cancer group were all significant in the analysis. In addition, we investigated whether the PC ratio differed according to age and staging in pancreatic cancer patients. Interestingly, the PC ratio was lower in the advanced stage group than in the early-stage group. CONCLUSION: Our results suggest that, irrespective of the degree, ectopic fat infiltration in the pancreas could be a specific clinical phenotype of serious pancreatic diseases, including pancreatic cancer, especially in high-risk patients.
ABSTRACT
OBJECTIVES: Failed implant removal using a high-frequency electrosurgical device (HFED) has been reported to be less invasive than other surgical techniques. We sought to clarify the mechanism of removal torque reduction in an implant by heating with HFED. MATERIALS AND METHODS: Sixty-eight Wistar rats received titanium implants on the maxillary bone 4 weeks after extraction of the first and second molars. The control group was sacrificed 6 weeks after implant installation. In the experimental group, the implant was heated by HFED for 10 s using three different power outputs, and samples were collected at 3, 7, and 14 days after heating. Removal torque measurement and histological analysis were performed in the control and experimental groups. Implant surfaces were observed using an electron-probe microanalyzer (EPMA). Data were analyzed using Mann-Whitney U test at a significance level of 5%. RESULTS: The removal torque could not be measured in the control group due to fracture of the implant. After heating, the removal torque was measurable without fracture and decreased significantly at 14 days as compared with that at 3 days (p < .05). Heating with "min" power output resulted in a significantly smaller blank lacunae area and fewer osteoclasts at 14 days after heating (p < .05). EPMA revealed bone matrix adherence to outer surface of heated implant. CONCLUSIONS: After heating, an enlarged area of blank lacunae around the implant and an increased number of osteoclasts into the bone marrow cavity were observed, which may have contributed to the reduction in removal torque.
Subject(s)
Dental Implants , Osseointegration , Animals , Device Removal , Electrosurgery , Heating , Implants, Experimental , Rats , Rats, Wistar , Surface Properties , Tibia , Titanium , TorqueABSTRACT
BACKGROUND: This study aimed to clarify the effects of underlying diseases on clinical outcomes of patients aboard a world cruise ship. METHODS: This prospective cohort study included patients who sought physician consultations at an onboard clinic on a 105-day world cruise (September-December 201X) on a ship chartered by a Japanese travel agency. Multivariable logistic regression analysis was performed to ascertain whether any concurrent disease, such as hypertension, was associated with additional onboard treatment by the primary physician or serious events, including unexpected final disembarkation, temporary disembarkation for hospitalization ashore, shore-side referral, and onboard clinic admission. RESULTS: Of 313 patients, 182 (58%) had at least one underlying disease. Sixty-eight (22%) required additional treatment, and 24 (8%) experienced serious events. After adjusting for age, sex, and underlying diseases, the 60-69- and 70-74-year age groups had a lower risk of serious events than the ≤59-year age group (odds ratio [OR], 95% confidence interval [CI]: 0.24, 0.069-0.81; p = 0.022 and 0.045, 0.0051-0.47; p = 0.0055). Underlying disease was associated with serious events (OR, 95% CI: 3.2, 1.1-9.5; p = 0.036). CONCLUSIONS: Unexpected events can occur in patients on world cruises regardless of age. Preexisting diseases may confer higher risk of serious events.
Subject(s)
Ships , Travel , Hospitalization , Humans , Prospective Studies , Referral and ConsultationABSTRACT
Synthesis of (+)-muconin isolated from Rollinia mucosa (Annonaceae) was achieved. Stereoselective construction of a tetrahydrofuran-terahydropyran (THF-THP) ring moiety was performed using diastereoselective oxypalladation in the presence of CuCl2. The cross-coupling reaction of the THF-THP moiety with the γ-lactone portion followed by reduction of the enyne and removal of the protecting groups afforded (+)-muconin.
Subject(s)
Annonaceae , Lactones , Fatty Alcohols , StereoisomerismABSTRACT
Synthesis of (+)-solenopsin, a 2,6-disubstituted piperidine alkaloid, isolated from fire ants (Solenopsis), was achieved. Stereoselective construction of trans-2,6-piperidine ring moiety was performed using palladium-catalyzed cyclization. Chain elongation using Grubbs 2nd catalyst followed by the reduction of double bond and the deprotection of the Cbz group afforded (+)-solenopsin.
Subject(s)
Alkaloids/chemistry , Alkaloids/chemical synthesis , Palladium/chemistry , Alkylation , Catalysis , Chemistry Techniques, Synthetic , Cyclization , Models, Molecular , Molecular Conformation , StereoisomerismABSTRACT
PURPOSE: The purpose of this study was to determine whether removing the superstructure of the implant bridge in cases of full-arch implant restorations for edentulous atrophic arches at the abutment level during professional mechanical plaque removal (PMPR) affects bacterial counts. METHODS: This crossover clinical trial included 20 patients who received screw-retained prostheses at the abutment level. Patients were randomly assigned to two groups and received PMPR with or without removal of the superstructure. After a three-month washout period, the type of treatment was reversed between the groups. Bacterial counts around the cylinder and abutment were measured and compared before and after PMPR. RESULTS: Bacterial numbers around the cylinder and abutment were significantly reduced after PMPR as compared with before PMPR regardless of whether the superstructure was removed (p <0.05). However the ratio of subjects with bacteria at 1.0 × 105 colony forming unit/ml (cfu/ml) or more after PMPR was significantly higher when the superstructure was not removed (p < 0.05). Among patients with bacterial counts of less than 10 × 105 cfu/ml, bacterial loads were reduced to less than 1.0 × 105 cfu/ml even when superstructures were not removed. Among patients with bacterial load of >10 × 105 cfu/ml, bacterial numbers were not reduced to <1.0 × 105 cfu/ml when PMPR was performed without removing the superstructure. CONCLUSIONS: Removal of the superstructure in cases of full-arch implant restorations for edentulous atrophic arches during PMPR reduces bacterial numbers around the implant bridge at the abutment level.
Subject(s)
Dental Implants , Bacterial Load , Dental Abutments , Dental Prosthesis, Implant-Supported , HumansABSTRACT
OBJECTIVES: We aimed to identify the occurrence and risk factors for unplanned catheter removal due to catheter-associated complications and the effects on catheter survival probability in a PICU. DESIGN: Retrospective, single-center, observational study of cases involving conventional central venous catheters or peripherally inserted central venous catheters. SETTING: The PICU of a tertiary children's hospital. PATIENTS: Consecutive PICU patients with central venous catheters between April 2016 and February 2019. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified unplanned catheter removals that were related to central line-associated bloodstream infection, thrombosis, and mechanical complications. During the study period, 582 central venous catheters and 474 peripherally inserted central venous catheters were identified. The median durations of catheter placement were 4.0 days for central venous catheters and 13.0 days for peripherally inserted central venous catheters (p < 0.001), and unplanned catheter removals due to catheter-associated complications were in 52 (8.9%) central venous catheter cases and 132 (27.8%) peripherally inserted central venous catheter cases (p < 0.001) (15.0 and 16.0 per 1,000 catheter-days, respectively [p = 0.75]). Unplanned catheter removal was associated with a peripheral catheter tip position among both central venous catheters and peripherally inserted central venous catheters (p < 0.001 and p = 0.001), and it was associated with surgical patient status among peripherally inserted central venous catheters (p = 0.009). In contrast, the use of ultrasound-guided insertion was associated with a lower occurrence of unplanned catheter removal among peripherally inserted central venous catheters (p = 0.01). With regard to catheter survival probability, there was no significant difference between central venous catheters and peripherally inserted central venous catheters (p = 0.23). However, peripherally inserted central venous catheters had a lower occurrence of central line-associated bloodstream infection than central venous catheters (p = 0.03), whereas there was no significant difference in the rates of thrombosis (p = 0.29) and mechanical complications (p = 0.84) between central venous catheters and peripherally inserted central venous catheters. CONCLUSIONS: In a PICU, peripherally inserted central venous catheters had lower occurrence of central line-associated bloodstream infection than central venous catheters; however, similar catheter survival probabilities were observed between both catheters. A central catheter tip position for both catheters and ultrasound-guided insertion for peripherally inserted central venous catheters may help limit unplanned catheter removal due to catheter-associated complications.
Subject(s)
Catheter-Related Infections , Catheterization, Central Venous , Catheterization, Peripheral , Central Venous Catheters , Catheter-Related Infections/epidemiology , Catheter-Related Infections/etiology , Catheterization, Central Venous/adverse effects , Catheterization, Peripheral/adverse effects , Catheters, Indwelling , Central Venous Catheters/adverse effects , Child , Humans , Intensive Care Units, Pediatric , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVES: To identify the effects of healthcare-associated infections on length of PICU stay and mortality. DESIGN: Retrospective, single-center, observational study. SETTING: PICU of a tertiary children's hospital. PATIENTS: Consecutive patients who stayed greater than 48 hours in the PICU between January 2013 and December 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data were retrospectively collected from medical records. We identified occurrences of common healthcare-associated infections, including bloodstream infection, pneumonia, and urinary tract infection, defined according to the 2008 definitions of the Centers for Disease Control and Prevention and National Healthcare Safety Network. We assessed the effects of each healthcare-associated infection on length of PICU stay and PICU mortality using multivariable analysis. Among 1,622 admissions with a PICU stay greater than 48 hours, the median age was 299 days and male patients comprised 51% of admissions. The primary diagnostic categories were cardiovascular (58% of admissions), respiratory (21%), gastrointestinal (8%), and neurologic/muscular (6%). The median length of PICU stay was 6 days, and the PICU mortality rate was 2.5%. A total of 167 healthcare-associated infections were identified, including 67 bloodstream infections (40%), 43 pneumonias (26%), and 57 urinary tract infections (34%). There were 152 admissions with at least one healthcare-associated infection (9.4% of admissions with a stay > 48 hr). On multivariable analysis, although each healthcare-associated infection was not significantly associated with mortality, bloodstream infection was associated with an extra length of PICU stay of 10.2 days (95% CI, 7.9-12.6 d), pneumonia 14.2 days (11.3-17.2 d), and urinary tract infection 6.5 days (4.0-9.0 d). Accordingly, 9.7% of patient-days were due to these three healthcare-associated infections among patients with a stay greater than 48 hours. CONCLUSIONS: Although healthcare-associated infections were not associated with PICU mortality, they were associated with extra length of PICU stay. As 9.7% of patient-days were due to healthcare-associated infections, robust prevention efforts are warranted.
Subject(s)
Cross Infection/mortality , Hospital Mortality , Intensive Care Units, Pediatric/statistics & numerical data , Length of Stay/statistics & numerical data , Case-Control Studies , Child, Preschool , Female , Humans , Infant , Male , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVES: In pediatric patients, indwelling peripheral venous catheters are sometimes displaced to extravascular positions, causing infiltration or extravasation. No reliable techniques are available to confirm accurate IV catheterization. However, ultrasonographic detection of micro-bubble turbulence in the right atrium after saline injection has been reported to be useful in confirming central venous catheter positions in both adults and children. This study evaluated whether this micro-bubble detection test can offer better confirmation of peripheral venous catheter positions compared with the smooth saline injection technique in pediatric patients. DESIGN: Randomized controlled study. SETTING: Single tertiary PICU. PATIENTS: Pediatric patients (weighing < 15 kg) who already had or required a peripheral venous catheter. INTERVENTIONS: Patients were randomly allocated to either of the two groups (150 patients per group): undergoing either the micro-bubble detection test (M group) or the smooth saline injection test (S group). MEASUREMENTS AND MAIN RESULTS: The peripheral venous catheters were confirmed to be IV located in the final position in 137 and 139 patients in the M and S groups, respectively. In properly located catheters, the tests were positive in 100% (n = 137/137; sensitivity, 100%; 95% CI, 97.8-100), and in 89% (n = 124/139; 95% CI, 82.8-93.8) of the M and S groups, respectively (p = 0.0001). Among the catheters located in extravascular positions, the tests were negative in 100% (n = 13/13; specificity, 100%; 95% CI, 79.4-100), and in 64% (n = 7/11; 95% CI, 30.8-89.1) of the M and S groups, respectively (p = 0.017). CONCLUSIONS: The micro-bubble detection test is a useful technique for detecting extravasation and confirming proper positioning of peripheral IV catheters in pediatric patients.
Subject(s)
Catheterization, Peripheral/methods , Catheters, Indwelling , Contrast Media , Heart Atria/diagnostic imaging , Microbubbles , Child, Preschool , Female , Humans , Infant , Male , Prospective Studies , Ultrasonography/methodsABSTRACT
Although many diagnostic and therapeutic modalities for pancreatic cancer have been proposed, an urgent need for improved therapeutic strategies remains. Oligonucleotide therapeutics, such as those based on antisense RNAs, small interfering RNA (siRNA), microRNA (miRNA), aptamers, and decoys, are promising agents against pancreatic cancer, because they can identify a specific mRNA fragment of a given sequence or protein, and interfere with gene expression as molecular-targeted agents. Within the past 25 years, the diversity and feasibility of these drugs as diagnostic or therapeutic tools have dramatically increased. Several clinical and preclinical studies of oligonucleotides have been conducted for patients with pancreatic cancer. To support the discovery of effective diagnostic or therapeutic options using oligonucleotide-based strategies, in the absence of satisfactory therapies for long-term survival and the increasing trend of diseases, we summarize the current clinical trials of oligonucleotide therapeutics for pancreatic cancer patients, with underlying preclinical and scientific data, and focus on the possibility of oligonucleotides for targeting pancreatic cancer in clinical implications.
Subject(s)
Oligonucleotides, Antisense/therapeutic use , Pancreatic Neoplasms/drug therapy , Animals , Aptamers, Nucleotide/therapeutic use , Clinical Trials as Topic , Humans , MicroRNAs/therapeutic use , RNA, Small Interfering/therapeutic useABSTRACT
PURPOSE: This study analyzed risk factors for post-loading implant loss in cases of implant-supported prostheses applied to edentulous jaws of Japanese patients. METHODS: In total, 245 dental implant fixtures placed in 54 edentulous jaws of 46 patients performed at Niigata University Hospital were retrospectively analyzed. Kaplan-Meier curves were used to estimate the cumulative survival rate (SR) of implants, and multiple Cox regression analysis was used to identify predictive factors of implant loss. The following risk factors for implant failure were examined: age, sex, survival time, implant length, implant location, smoking habit, bone density, bone augmentation, opposing dentition, loading period, and type of final restoration. The Cochran-Mantel-Haenszel test was used to examine difference in survival curves of the extracted predictors. RESULTS: Sixteen implants failed during the observation period (SR=92.8 %). Multiple Cox regression analysis revealed that male sex [hazard ratio (HR)=16.1; p=0.007] and use of maxillary removable restorations (HR=12.7; p<0.000) were risk factors for implant failure. Other factors had no significant effect on implant failure. The SR of implants for males (SR=86.9%) was significantly lower than that for females (SR=99.1%). The SR of implants for maxillary removable restorations (SR=76.4%) was significantly lower than for maxillary fixed restorations (SR=99.1%) and mandibular fixed restorations (SR=97.8%). CONCLUSIONS: Maxillary implants with removable restorations and male sex were risk factors for implant failure among Japanese edentulous patients.
Subject(s)
Dental Prosthesis, Implant-Supported , Dental Restoration Failure , Denture, Partial, Removable , Jaw, Edentulous/rehabilitation , Age Factors , Aged , Asian People , Female , Humans , Male , Maxilla , Proportional Hazards Models , Retrospective Studies , Risk Factors , Sex FactorsABSTRACT
A catalytic amount of a sterically and electronically tuned diarylsulfonamide promoted allylic and benzylic C-H arylations in cooperation with a visible light photoredox catalyst. This is the first example of the catalytic use of a sulfonamidyl radical to promote the hydrogen atom transfer process.