Oral rinses containing chemotherapeutic agents, such as cetylpyridinium chloride （CPC）, can alleviate plaque-induced gingival infections, but how oral microbiota respond to these treatments in human population remai...Oral rinses containing chemotherapeutic agents, such as cetylpyridinium chloride （CPC）, can alleviate plaque-induced gingival infections, but how oral microbiota respond to these treatments in human population remains poorly understood. Via a double- blinded, randomised controlled trial of 91 subjects, the impact of CPC-containing oral rinses on supragingival plaque was investigated in experimental gingivitis, where the subjects, after a 21-day period of dental prophylaxis to achieve healthy gingivae, received either CPC rinses or water for 21 days. Within-subject temporal dynamics of plaque microbiota and symptoms of gingivitis were profiled via 16S ribosomal DNA gene pyrosequencing and assessment with the Mazza gingival index. Cetylpyridinium chloride conferred gingival benefits, as progression of gingival inflammation resulting from a lack of dental hygiene was significantly slower in the mouth rinse group than in the water group due to inhibition of 17 gingivitis-enriched bacterial genera. Tracking of plaque a and β diversity revealed that CPC treatment prevents acquisition of new taxa that would otherwise accumulate but maintains the original biodiversity of healthy plaques. Furthermore, CPC rinses reduced the size, local connectivity and microbiota-wide connectivity of the bacterial correlation network, particularly for nodes representing gingivitis- enriched taxa. The findings of this study provide mechanistic insights into the impact of oral rinses on the progression and maturation of dental plaque in the natural human population.展开更多
Dental restorative materials with antimicrobial properties can inhibit bacterial colonization, which may result in a reduction of caries at tooth-filling interaction zones. This study aimed to develop antibacterial gl...Dental restorative materials with antimicrobial properties can inhibit bacterial colonization, which may result in a reduction of caries at tooth-filling interaction zones. This study aimed to develop antibacterial glass-ionomer cements （GIC） containing a quaternary ammonium monomer （dimethylaminododecyl methacrylate, DMADDM）, and to investigate their effect on material performance and antibacterial properties. Different mass fractions （0, 1.1% and 2.2%） of DMADDM were incorporated into the GIC. The flexure strength, surface charge density, surface roughness and fluoride release were tested. A Streptococcus mutans biofilm model was used. Exopolysaccharides （EPS） staining was used to analyze the inhibitory effect of DMADDM on the biofilm matrix. In addition, biofilm metabolic activity, lactic acid metabolism and the expression of glucosyltransferase genes g/fB, gtfC and gtfD were measured. GIC containing 1.1% and 2.2% DMADDM had flexural strengths matching those of the commercial control （P〉0.1）. DMADDM was able to increase the surface charge density but reduced surface roughness （P〈0.05）. The incorporation of 1.1% and 2.2% DMADDM elevated the release of fluoride by the GIC in the first 2 days （P〈0.05）. The novel DMADDM-modified GIC significantly reduced biofilm metabolic activity （P〈 0.05） and decreased lactic acid production （P〈 0.05）. The quantitative polymerase chain reaction （qPCR） results showed that the expression of gtfB, g/fC and gtfD decreased when mass fractions of DMADDM increased （P〈0.05）. EPS staining showed that both the bacteria and EPS in biofilm decreased in the DMADDM groups. The incorporation of DMADDM could modify the properties of GIC to influence the development of S. mutans biofilms. In this study, we investigated the interface properties of antibacterial materials for the first time. GIC containing DMADDM can improve material performance and antibacterial properties and may contribute to the better management of secondary caries.展开更多
BACKGROUND Obesity is a risk factor for colorectal cancer,yet metabolic distinctions between healthy right and left colon tissue,before cancer is diagnosed,remains largely unknown.This study compared right-ascending a...BACKGROUND Obesity is a risk factor for colorectal cancer,yet metabolic distinctions between healthy right and left colon tissue,before cancer is diagnosed,remains largely unknown.This study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight,overweight,and obese adults.AIM To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer risk.METHODS Global,non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite profiles.The colon tissue and stool metabolome of healthy adults(n=24)was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal cancer.RESULTS Ascending and descending colon contained 504 host,food,and microbiotaderived metabolites from normal weight,overweight and obese adults grouped according to body mass index.Amino acids,lipids,and nucleotides were among the chemical types that further differentiated from the stool metabolite profiles.Normal weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations,whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults(P<0.05).Obese adults had trimethylamine N-oxide,endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending colon.Primary and secondary bile acids,vitamins,and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese adults.CONCLUSION There were metabolite profile differences between right-ascending and leftdescending colon tissue in healthy adults.Colon lipids and other metabolites in obese and overweight adults were distinguished from normal weight participants and associated with gut inflammation,nutrient absorption,and products of microbiota metabolism.展开更多
Melanoma is the most aggressive form of skin cancer.Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic b...Melanoma is the most aggressive form of skin cancer.Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation,there is increasing evidence that endoplasmic reticulum(ER) stress-associated pathways play a role in the potentiation,initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment.展开更多
Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory co...Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the realtime feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a costeffectiveness analysis is also necessary.展开更多
AIM To evaluate sustained viral response(SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus(HCV) patients with RNA < 6 million IU/m L.METHODS We performed a retrospective c...AIM To evaluate sustained viral response(SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus(HCV) patients with RNA < 6 million IU/m L.METHODS We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir(LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/m L. Primary outcome was an achievement of SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of treatment failure and adverse events during treatment.RESULTS Total 736 patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state of 53% was determined by clinical judgment(imaging, AST, platelet count) and 47% had documented liver fibrosis testing(biopsy, vibration-controlled transient elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12 was seen between patients whose non-cirrhotic state was determined by clinical judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by clinical judgment based on simple, non-invasive tests were not associated with lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA viral load was 0.734(P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/m L was identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA < 2.2 million IU/m L was associated with significantly higher SVR 98% with OR = 0.22(95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA ≥ 2.2 million IU/m L. No death or morbidities were reported.CONCLUSION Our outcomes validate safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV genotype 1 patients with HCV RNA < 6 million IU/m L.展开更多
In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders incl...In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients’ sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor (GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.展开更多
Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers,breast and lung,in that routine surveillance is recommended with the specific intent of detecting liver and...Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers,breast and lung,in that routine surveillance is recommended with the specific intent of detecting liver and lung metastases and undertaking liver and lung resections for their removal.We trace the history of this approach to colorectal cancer by reviewing evidence for effectiveness from the 1950s to the present day.Our sources included published citation network analyses,the documented proposal for randomised trials,large systematic reviews,and meta-analysis of observational studies.The present consensus position has been adopted on the basis of a large number of observational studies but the randomised trials proposed in the 1980s and 1990s were either not done,or having been done,were not reported.Clinical opinion is the mainstay of current practice but in the absence of randomised trials there remains a possibility of selection bias.Randomised controlled trials(RCTs)are now routine before adoption of a new practice but RCTs are harder to run in evaluation of already established practice.One such trial is recruiting and shows that controlled trial are possible.展开更多
Length of stay in treatment is thought to be the best predictors for long-term recovery from substance use disorders. The objective of this study was to examine the relationship between participation in mind-body-spir...Length of stay in treatment is thought to be the best predictors for long-term recovery from substance use disorders. The objective of this study was to examine the relationship between participation in mind-body-spirit (MBS) therapeutic programs and length of stay in a residential treatment facility. A retrospective analysis of data from 1719 subjects who were admitted to a 30-day residential program for substance use disorders (SUD) was conducted. Subjects participated in MBS programs that included yoga, acupuncture and meditation. We examined the effects of subject participation in MBS programs for subjects who left against staff advice (ASA) and those who successfully completed the residential program. A higher percentage of subjects with severe heroin use disorder left ASA compared with subjects with severe alcohol use disorder (16% vs. 9%, respectively). Most subjects from both substance groups who failed to complete the 30-day treatment program, left within the first two weeks of stay (59% of alcohol group and 75% of heroin group);however, again, the percentage of heroin users leaving during the first two weeks was significantly greater compared with that of alcohol subjects. We found a highly significant, positive correlation (r = 0.56, p < 0.01) and a statistically significant increase in LOS for all subjects, regardless of the substance type, and the number of MBS program sessions attended showing an association between MBS participation and increased LOS. These data support the inclusion of MBS programs as part of a comprehensive treatment strategy for SUD in combination with traditional counseling to help develop a sustainable long-term recovery.展开更多
Objective: Women’s preferences for the mode of delivery provide clues on their knowledge and perceptions of anticipated risk of childbirth complications.?The objective was toinvestigate?incongruence between preferred...Objective: Women’s preferences for the mode of delivery provide clues on their knowledge and perceptions of anticipated risk of childbirth complications.?The objective was toinvestigate?incongruence between preferred mode of delivery and risk of adverse pregnancy outcomes. Methods: Through a cross-sectional study, data were?collected from 327?women admitted to Mulago hospital. Data included socio-demographic?characteristics, past medical, gynaecological and obstetric history, pregnancy complications, knowledge of pregnancy complications and preferred mode of delivery. The preferred mode of delivery and knowledge of related risks for adverse pregnancy outcomes were compared. Results: The mean age of participants was 24.7 years (±5.9), ranging?14?-?43 years, of whom 41.4% were nulliparous. The preferred mode of delivery was vaginal (84.1%). Incongruence?(preference for a mode of delivery that did not correspond to expected or anticipated risks) occurred in 88 (26.9%) of the women, and was associated with having secondary school or higher level of education (OR 2.49, CI 1.52?-?4.08) and history of previous vaginal delivery (OR 3.82,?CI 1.94?-?7.49). Conclusion: One in four women had incongruence between preferred mode of delivery and risks of adverse pregnancy outcomes, which called?for urgent interventions to improve decision-making about intrapartum care.展开更多
High-quality DNA extraction is a crucial step in metagenomic studies.Bias by different isolation kits impairs the comparison across datasets.A trending topic is,however,the analysis of multiple metagenomes from the sa...High-quality DNA extraction is a crucial step in metagenomic studies.Bias by different isolation kits impairs the comparison across datasets.A trending topic is,however,the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases.We thus collected bile,stool,saliva,plaque,sputum,and conjunctival swab samples and performed DNA extraction with three commercial kits.For each combination of the specimen type and DNA extraction kit,20-gigabase(Gb)metagenomic data were generated using short-read sequencing.While profiles of the specimen types showed close proximity to each other,we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits.No kit outperformed all selected kits on every specimen.We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit.Depending on the specimen,our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution,but DNA-based identification is superior to identification by mass spectrometry.Finally,longread nanopore sequencing confirmed the results(correlation coefficient>0.98).Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients.展开更多
The micro- and nanostructures of human dental enamel were investigated by transmission electron microscopy （TEM） and electron backscatter diffraction （EBSD）. For this purpose, TEM slices were prepared from teeth b...The micro- and nanostructures of human dental enamel were investigated by transmission electron microscopy （TEM） and electron backscatter diffraction （EBSD）. For this purpose, TEM slices were prepared from teeth by focused ion-beam milling. These slices enabled TEM and transmission-EBSD （t-EBSD） investigations to be performed, while standard EBSD on bulk tooth samples resulted only in Kikuchi patterns. On the TEM slices, t-EBSD enabled automated mapping. The TEM images and the EBSD data dearly elucidated the arrangement of the hydroxyapatite crystals on the nanometer scale. Information regarding the crystallographic orientation of the apatite grains enabled the deduction of novel nanotechnological building principles of the enamel structure based on a chain-like arrangement of the crystallites.展开更多
Objective: To evaluate the surgical methods and the outcome of management for traumatic arterial aneurysm (TAA) and traumatic arterioveneus fistula (TAVF).Methods: A total of 121 patients with TAA or TAVF were treated...Objective: To evaluate the surgical methods and the outcome of management for traumatic arterial aneurysm (TAA) and traumatic arterioveneus fistula (TAVF).Methods: A total of 121 patients with TAA or TAVF were treated by surgery. Clinical, operative and postoperative data were collected and analyzed retrospectively.Results: The surgical techniques includedaneurysmectomy and arterial end-to-end anastomosis or vascular grafting or artery ligation, aneurysm ligation and bypass, vascular repair, fistula excision and vascular ligation or vascular grafting or repair and so on. One patient died (0.83%). The follow-up rates of TAA and TAVF were 65.7% and 60% respectively.Conclusions: Complicated TAA and TAVF in different sites should be treated with different methods.展开更多
基金funded by a joint research program between the Chinese Academy of Sciences and Procter & Gamble
文摘Oral rinses containing chemotherapeutic agents, such as cetylpyridinium chloride （CPC）, can alleviate plaque-induced gingival infections, but how oral microbiota respond to these treatments in human population remains poorly understood. Via a double- blinded, randomised controlled trial of 91 subjects, the impact of CPC-containing oral rinses on supragingival plaque was investigated in experimental gingivitis, where the subjects, after a 21-day period of dental prophylaxis to achieve healthy gingivae, received either CPC rinses or water for 21 days. Within-subject temporal dynamics of plaque microbiota and symptoms of gingivitis were profiled via 16S ribosomal DNA gene pyrosequencing and assessment with the Mazza gingival index. Cetylpyridinium chloride conferred gingival benefits, as progression of gingival inflammation resulting from a lack of dental hygiene was significantly slower in the mouth rinse group than in the water group due to inhibition of 17 gingivitis-enriched bacterial genera. Tracking of plaque a and β diversity revealed that CPC treatment prevents acquisition of new taxa that would otherwise accumulate but maintains the original biodiversity of healthy plaques. Furthermore, CPC rinses reduced the size, local connectivity and microbiota-wide connectivity of the bacterial correlation network, particularly for nodes representing gingivitis- enriched taxa. The findings of this study provide mechanistic insights into the impact of oral rinses on the progression and maturation of dental plaque in the natural human population.
基金supported by a National Natural Science Foundation of China grant 81372889 (Lei Cheng), 81430011 (Xue-dong Zhou)the Program for New Century Excellent Talents in University (Lei Cheng)+3 种基金a Youth Grant of the Science and Technology Department of Sichuan Province, China 2014JQ0033 (Lei Cheng)the International Science and Technology Cooperation Program of China 2014DFE30180 (Xue-dong Zhou)NIH R01 DE17974 (Hockin HK Xu)a Seed Grant (Hockin HK Xu) from the University of Maryland School of Dentistry
文摘Dental restorative materials with antimicrobial properties can inhibit bacterial colonization, which may result in a reduction of caries at tooth-filling interaction zones. This study aimed to develop antibacterial glass-ionomer cements （GIC） containing a quaternary ammonium monomer （dimethylaminododecyl methacrylate, DMADDM）, and to investigate their effect on material performance and antibacterial properties. Different mass fractions （0, 1.1% and 2.2%） of DMADDM were incorporated into the GIC. The flexure strength, surface charge density, surface roughness and fluoride release were tested. A Streptococcus mutans biofilm model was used. Exopolysaccharides （EPS） staining was used to analyze the inhibitory effect of DMADDM on the biofilm matrix. In addition, biofilm metabolic activity, lactic acid metabolism and the expression of glucosyltransferase genes g/fB, gtfC and gtfD were measured. GIC containing 1.1% and 2.2% DMADDM had flexural strengths matching those of the commercial control （P〉0.1）. DMADDM was able to increase the surface charge density but reduced surface roughness （P〈0.05）. The incorporation of 1.1% and 2.2% DMADDM elevated the release of fluoride by the GIC in the first 2 days （P〈0.05）. The novel DMADDM-modified GIC significantly reduced biofilm metabolic activity （P〈 0.05） and decreased lactic acid production （P〈 0.05）. The quantitative polymerase chain reaction （qPCR） results showed that the expression of gtfB, g/fC and gtfD decreased when mass fractions of DMADDM increased （P〈0.05）. EPS staining showed that both the bacteria and EPS in biofilm decreased in the DMADDM groups. The incorporation of DMADDM could modify the properties of GIC to influence the development of S. mutans biofilms. In this study, we investigated the interface properties of antibacterial materials for the first time. GIC containing DMADDM can improve material performance and antibacterial properties and may contribute to the better management of secondary caries.
基金Supported by the Cancer Cure Foundation and the University of Colorado Cancer Center Support Grant,Division of Cancer Control and Prevention(Aurora,CO),No.P30CA046934
文摘BACKGROUND Obesity is a risk factor for colorectal cancer,yet metabolic distinctions between healthy right and left colon tissue,before cancer is diagnosed,remains largely unknown.This study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight,overweight,and obese adults.AIM To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer risk.METHODS Global,non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite profiles.The colon tissue and stool metabolome of healthy adults(n=24)was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal cancer.RESULTS Ascending and descending colon contained 504 host,food,and microbiotaderived metabolites from normal weight,overweight and obese adults grouped according to body mass index.Amino acids,lipids,and nucleotides were among the chemical types that further differentiated from the stool metabolite profiles.Normal weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations,whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults(P<0.05).Obese adults had trimethylamine N-oxide,endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending colon.Primary and secondary bile acids,vitamins,and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese adults.CONCLUSION There were metabolite profile differences between right-ascending and leftdescending colon tissue in healthy adults.Colon lipids and other metabolites in obese and overweight adults were distinguished from normal weight participants and associated with gut inflammation,nutrient absorption,and products of microbiota metabolism.
文摘Melanoma is the most aggressive form of skin cancer.Disrupted intracellular signaling pathways are responsible for melanoma's extraordinary resistance to current chemotherapeutic modalities. The pathophysiologic basis for resistance to both chemo- and radiation therapy is rooted in altered genetic and epigenetic mechanisms that, in turn, result in the impairing of cell death machinery and/or excessive activation of cell growth and survival-dependent pathways. Although most current melanoma therapies target mitochondrial dysregulation,there is increasing evidence that endoplasmic reticulum(ER) stress-associated pathways play a role in the potentiation,initiation and maintenance of cell death machinery and autophagy. This review focuses on the reliability of ER-associated pathways as therapeutic targets for melanoma treatment.
文摘Vascular targeted photochemotherapy(VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer(LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the realtime feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a costeffectiveness analysis is also necessary.
文摘AIM To evaluate sustained viral response(SVR) of 8-wk ledipasvir/sofosbuvir therapy among non-cirrhotic, genotype-1 hepatitis C virus(HCV) patients with RNA < 6 million IU/m L.METHODS We performed a retrospective cohort study to examine SVR rates, predictors of treatment failure and safety analysis of 8-wk ledipasvir/sofosbuvir(LDV/SOF) therapy among non-cirrhotic, genotype 1 HCV patients with viral load < 6 million IU/m L. Primary outcome was an achievement of SVR at 12 wk after treatment. Secondary outcomes were identifying predictors of treatment failure and adverse events during treatment.RESULTS Total 736 patients: 55% males, 51% Caucasians and 65% were genotype 1a. Non-cirrhotic state of 53% was determined by clinical judgment(imaging, AST, platelet count) and 47% had documented liver fibrosis testing(biopsy, vibration-controlled transient elastography, serum biomarkers). Overall SVR12 was 96%. No difference in SVR12 was seen between patients whose non-cirrhotic state was determined by clinical judgment and patients who had fibrosis testing. Age groups, gender, ethnicity and genotype 1 subtype did not predict SVR. Non-cirrhotic state determined by clinical judgment based on simple, non-invasive tests were not associated with lower SVR [OR = 1.02, 95%CI: 0.48-2.17, P = 0.962]. The AUROC for hepatitis C RNA viral load was 0.734(P < 0.001, 95%CI: 0.66-0.82). HCV RNA 2.2 million IU/m L was identified as the cutoff value with sensitivity 73% and specificity 64%. HCV RNA < 2.2 million IU/m L was associated with significantly higher SVR 98% with OR = 0.22(95%CI: 0.1-0.49, P < 0.001) compared to SVR 92% in HCV RNA ≥ 2.2 million IU/m L. No death or morbidities were reported.CONCLUSION Our outcomes validate safety and effectiveness of 8-wk LDV/SOF therapy in non-cirrhotic, untreated HCV genotype 1 patients with HCV RNA < 6 million IU/m L.
文摘In addition to its contributing role in the development of chronic liver diseases, chronic hepatitis C virus (HCV) infection is associated with extrahepatic manifestations, particularly, cutaneous-based disorders including those with pruritus as a symptom. Pruritus is frequently associated with the development of chronic liver diseases such as cholestasis and chronic viral infection, and the accumulation of bile acids in patients’ sera and tissues as a consequence of liver damage is considered the main cause of pruritus. In addition to their role in dietary lipid absorption, bile acids can trigger the activation of specific receptors, such as the G protein-coupled bile acid receptor (GPBA/ TGR5). These types of receptors are known to play a crucial role in the modulation of the systemic actions of bile acids. TGR5 expression in primary sensory neurons triggers the activation of the transient receptor potential vanilloid 1 (TRPV1) leading to the induction of pruritus by an unknown mechanism. Although the pathologic phenomenon of pruritus is common, there is no uniformly effective therapy available. Understanding the mechanisms regulating the occurrence of pruritus together with the conduction of large-scale clinical and evidence-based studies, may help to create a standard treatment protocol. This review focuses on the etiopathogenesis and treatment strategies of pruritus associated with chronic HCV infection.
基金Supported by The British Heart Foundation(to Fiorentino F)
文摘Clinical practice with respect to metastatic colorectal cancer differs from the other two most common cancers,breast and lung,in that routine surveillance is recommended with the specific intent of detecting liver and lung metastases and undertaking liver and lung resections for their removal.We trace the history of this approach to colorectal cancer by reviewing evidence for effectiveness from the 1950s to the present day.Our sources included published citation network analyses,the documented proposal for randomised trials,large systematic reviews,and meta-analysis of observational studies.The present consensus position has been adopted on the basis of a large number of observational studies but the randomised trials proposed in the 1980s and 1990s were either not done,or having been done,were not reported.Clinical opinion is the mainstay of current practice but in the absence of randomised trials there remains a possibility of selection bias.Randomised controlled trials(RCTs)are now routine before adoption of a new practice but RCTs are harder to run in evaluation of already established practice.One such trial is recruiting and shows that controlled trial are possible.
文摘Length of stay in treatment is thought to be the best predictors for long-term recovery from substance use disorders. The objective of this study was to examine the relationship between participation in mind-body-spirit (MBS) therapeutic programs and length of stay in a residential treatment facility. A retrospective analysis of data from 1719 subjects who were admitted to a 30-day residential program for substance use disorders (SUD) was conducted. Subjects participated in MBS programs that included yoga, acupuncture and meditation. We examined the effects of subject participation in MBS programs for subjects who left against staff advice (ASA) and those who successfully completed the residential program. A higher percentage of subjects with severe heroin use disorder left ASA compared with subjects with severe alcohol use disorder (16% vs. 9%, respectively). Most subjects from both substance groups who failed to complete the 30-day treatment program, left within the first two weeks of stay (59% of alcohol group and 75% of heroin group);however, again, the percentage of heroin users leaving during the first two weeks was significantly greater compared with that of alcohol subjects. We found a highly significant, positive correlation (r = 0.56, p < 0.01) and a statistically significant increase in LOS for all subjects, regardless of the substance type, and the number of MBS program sessions attended showing an association between MBS participation and increased LOS. These data support the inclusion of MBS programs as part of a comprehensive treatment strategy for SUD in combination with traditional counseling to help develop a sustainable long-term recovery.
文摘Objective: Women’s preferences for the mode of delivery provide clues on their knowledge and perceptions of anticipated risk of childbirth complications.?The objective was toinvestigate?incongruence between preferred mode of delivery and risk of adverse pregnancy outcomes. Methods: Through a cross-sectional study, data were?collected from 327?women admitted to Mulago hospital. Data included socio-demographic?characteristics, past medical, gynaecological and obstetric history, pregnancy complications, knowledge of pregnancy complications and preferred mode of delivery. The preferred mode of delivery and knowledge of related risks for adverse pregnancy outcomes were compared. Results: The mean age of participants was 24.7 years (±5.9), ranging?14?-?43 years, of whom 41.4% were nulliparous. The preferred mode of delivery was vaginal (84.1%). Incongruence?(preference for a mode of delivery that did not correspond to expected or anticipated risks) occurred in 88 (26.9%) of the women, and was associated with having secondary school or higher level of education (OR 2.49, CI 1.52?-?4.08) and history of previous vaginal delivery (OR 3.82,?CI 1.94?-?7.49). Conclusion: One in four women had incongruence between preferred mode of delivery and risks of adverse pregnancy outcomes, which called?for urgent interventions to improve decision-making about intrapartum care.
文摘High-quality DNA extraction is a crucial step in metagenomic studies.Bias by different isolation kits impairs the comparison across datasets.A trending topic is,however,the analysis of multiple metagenomes from the same patients to draw a holistic picture of microbiota associated with diseases.We thus collected bile,stool,saliva,plaque,sputum,and conjunctival swab samples and performed DNA extraction with three commercial kits.For each combination of the specimen type and DNA extraction kit,20-gigabase(Gb)metagenomic data were generated using short-read sequencing.While profiles of the specimen types showed close proximity to each other,we observed notable differences in the alpha diversity and composition of the microbiota depending on the DNA extraction kits.No kit outperformed all selected kits on every specimen.We reached consistently good results using the Qiagen QiAamp DNA Microbiome Kit.Depending on the specimen,our data indicate that over 10 Gb of sequencing data are required to achieve sufficient resolution,but DNA-based identification is superior to identification by mass spectrometry.Finally,longread nanopore sequencing confirmed the results(correlation coefficient>0.98).Our results thus suggest using a strategy with only one kit for studies aiming for a direct comparison of multiple microbiotas from the same patients.
文摘The micro- and nanostructures of human dental enamel were investigated by transmission electron microscopy （TEM） and electron backscatter diffraction （EBSD）. For this purpose, TEM slices were prepared from teeth by focused ion-beam milling. These slices enabled TEM and transmission-EBSD （t-EBSD） investigations to be performed, while standard EBSD on bulk tooth samples resulted only in Kikuchi patterns. On the TEM slices, t-EBSD enabled automated mapping. The TEM images and the EBSD data dearly elucidated the arrangement of the hydroxyapatite crystals on the nanometer scale. Information regarding the crystallographic orientation of the apatite grains enabled the deduction of novel nanotechnological building principles of the enamel structure based on a chain-like arrangement of the crystallites.
文摘Objective: To evaluate the surgical methods and the outcome of management for traumatic arterial aneurysm (TAA) and traumatic arterioveneus fistula (TAVF).Methods: A total of 121 patients with TAA or TAVF were treated by surgery. Clinical, operative and postoperative data were collected and analyzed retrospectively.Results: The surgical techniques includedaneurysmectomy and arterial end-to-end anastomosis or vascular grafting or artery ligation, aneurysm ligation and bypass, vascular repair, fistula excision and vascular ligation or vascular grafting or repair and so on. One patient died (0.83%). The follow-up rates of TAA and TAVF were 65.7% and 60% respectively.Conclusions: Complicated TAA and TAVF in different sites should be treated with different methods.
