Pub Date : 2015-06-04DOI: 10.1186/s12952-015-0029-5
Khaled K Abu-Amero, Inas Helwa, Abdulrahman Al-Muammar, Shelby Strickland, Michael A Hauser, R Rand Allingham, Yutao Liu
Background: Keratoconus (KC) is the most common primary ectatic disease of the cornea and a major indication for corneal transplant. To date, limited KC-associated-risk loci have been identified. Association has recently been suggested between KC and 8 single nucleotide polymorphisms (SNPs) in the genomic regions of FNDC3B, COL4A3, MPDZ-NF1B, RXRA-COL5A1, LCN12-PTGDS, FOXO1, and BANP-ZNF469. These SNPs are associated with central corneal thickness (CCT), a known risk factor to KC. We are questioning whether these SNPs are significantly associated with KC in a Saudi Arabian population. The study included 108 unrelated KC cases and 300 controls. Patients were diagnosed with KC according to the Schimpff-flow based elevation map of the cornea. DNA genotyping was done using probe-based allelic discrimination TaqMan assays. Allele frequencies were compared between the cases and controls.
Results: All SNPs were successfully genotyped with high efficiency (>95 %). The SNPs had no significant deviation in cases or controls from Hardy-Weinberg Equilibrium (HWE, p value > 0.05). None of the selected SNPs were significantly associated with KC in the Saudi Arabian population. However, we replicated the same trend of minor allele frequency (MAF) between cases and controls reported by a recent GWAS regarding the 5 SNPs rs4894535 (FNDC3B, chr3: 171995605), rs1536482 (RXRA-COL5A1, chr9: 137440528), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264), and rs2721051 (FOXO1, chr13: 41110884).
Conclusions: This is the first study investigating the association of these SNPs with KC in a population from Saudi Arabia. We replicated the same trend of MAF alteration of the association between the SNPs rs4894535 (FNDC3B, chr3: 171995605), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264) and rs2721051 (FOXO1, chr13: 41110884) and KC-risk as reported by a recently published GWAS. Consistently replicated population-based studies are necessary to identify and/or confirm genetic susceptibility for certain diseases. We acknowledge that the lack of significance in our study is due to our small sample size and insufficient statistical power; however our data still add to the body of evidence of potential KC-candidate SNPs. This report aims at supporting the possible association between CCT-associated SNPs and KC susceptibility.
{"title":"Case-control association between CCT-associated variants and keratoconus in a Saudi Arabian population.","authors":"Khaled K Abu-Amero, Inas Helwa, Abdulrahman Al-Muammar, Shelby Strickland, Michael A Hauser, R Rand Allingham, Yutao Liu","doi":"10.1186/s12952-015-0029-5","DOIUrl":"10.1186/s12952-015-0029-5","url":null,"abstract":"<p><strong>Background: </strong>Keratoconus (KC) is the most common primary ectatic disease of the cornea and a major indication for corneal transplant. To date, limited KC-associated-risk loci have been identified. Association has recently been suggested between KC and 8 single nucleotide polymorphisms (SNPs) in the genomic regions of FNDC3B, COL4A3, MPDZ-NF1B, RXRA-COL5A1, LCN12-PTGDS, FOXO1, and BANP-ZNF469. These SNPs are associated with central corneal thickness (CCT), a known risk factor to KC. We are questioning whether these SNPs are significantly associated with KC in a Saudi Arabian population. The study included 108 unrelated KC cases and 300 controls. Patients were diagnosed with KC according to the Schimpff-flow based elevation map of the cornea. DNA genotyping was done using probe-based allelic discrimination TaqMan assays. Allele frequencies were compared between the cases and controls.</p><p><strong>Results: </strong>All SNPs were successfully genotyped with high efficiency (>95 %). The SNPs had no significant deviation in cases or controls from Hardy-Weinberg Equilibrium (HWE, p value > 0.05). None of the selected SNPs were significantly associated with KC in the Saudi Arabian population. However, we replicated the same trend of minor allele frequency (MAF) between cases and controls reported by a recent GWAS regarding the 5 SNPs rs4894535 (FNDC3B, chr3: 171995605), rs1536482 (RXRA-COL5A1, chr9: 137440528), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264), and rs2721051 (FOXO1, chr13: 41110884).</p><p><strong>Conclusions: </strong>This is the first study investigating the association of these SNPs with KC in a population from Saudi Arabia. We replicated the same trend of MAF alteration of the association between the SNPs rs4894535 (FNDC3B, chr3: 171995605), rs7044529 (COL5A1, chr9: 137568051), rs11145951 (LCN12-PTGDS, chr9: 139860264) and rs2721051 (FOXO1, chr13: 41110884) and KC-risk as reported by a recently published GWAS. Consistently replicated population-based studies are necessary to identify and/or confirm genetic susceptibility for certain diseases. We acknowledge that the lack of significance in our study is due to our small sample size and insufficient statistical power; however our data still add to the body of evidence of potential KC-candidate SNPs. This report aims at supporting the possible association between CCT-associated SNPs and KC susceptibility.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4461978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33357039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-05-07DOI: 10.1186/s12952-015-0027-7
Carlo V Feo, Mattia Portinari, Michele Zuolo, Simone Targa, Vincenzo G Matarese, Roberta Gafà, Elena Forini, Giovanni Lanza
Background: A direct correlation between number of lymph nodes retrieved and evaluated after a colectomy for colorectal cancer and survival of the patient has been reported, and consensus guidelines recommend to assess at least 12 lymph nodes for adequate staging. Many factors (i.e., patients' and tumour characteristics, surgeon, and pathologist) may influence the evaluation of the presence of neoplastic disease in lymph nodes as well as the total number of lymph nodes examined. Preoperative endoscopic tattooing to mark the site of the tumour has recently been suggested to facilitate the retrieval of lymph nodes in colorectal specimens. The aim of this study was to investigate its association with adequate lymphadenectomy (≥12 nodes) after colorectal resection for cancer.
Results: All patients undergoing elective colorectal resection for cancer between 2009 and 2011 at the S. Anna University Hospital in Ferrara, Italy (N = 250) were retrospectively divided into two cohorts according to whether ink tattooing to mark the tumour site was performed during preoperative colonoscopy. The two cohorts were comparable regarding age, gender, body mass index, tumour location and size, TNM staging, and DNA microsatellite instability-high status. No difference between the tattoo (N = 107) and control (N = 143) groups could be detected in the rate of adequate lymphadenectomies performed (78% vs. 79%, p = 0.40). All factors known to influence lymph nodes retrieval from colorectal specimen were specifically evaluated. Rectal and colonic cancers were analysed together and separately. Full adjusted logistic regression analysis in patients who underwent colonic resection showed that right hemicolectomy (OR 4.72; CI95% 1.09-20.36) was the only factor associated to adequate lymphadenectomy. No association between ink tattooing performed preoperatively to mark the site of the tumour and adequate lymphadenectomy after colorectal resection was found with logistic regression analysis.
Conclusion: This study shows that preoperative ink tattooing utilized to mark the site of the tumour does not improve adequate lymphadenectomy and lymph nodes yield from colorectal cancer specimens. Further studies are therefore needed to determine if preoperative colonoscopic tattooing to mark the tumour site can refine staging.
背景:有报道称,结直肠癌结肠切除术后取回和评估的淋巴结数量与患者的存活率直接相关,共识指南建议至少评估 12 个淋巴结以进行充分分期。许多因素(如患者和肿瘤特征、外科医生和病理学家)都可能影响对淋巴结是否存在肿瘤性疾病的评估以及检查的淋巴结总数。最近有人建议术前在内镜上刺青标记肿瘤部位,以方便取回结直肠标本中的淋巴结。本研究的目的是调查其与结直肠癌切除术后淋巴结充分切除(≥12个)的关系:根据术前结肠镜检查时是否对肿瘤部位进行纹身标记,将 2009 年至 2011 年期间在意大利费拉拉 S. Anna 大学医院接受选择性结肠直肠癌切除术的所有患者(250 人)回顾性地分为两个队列。两组患者的年龄、性别、体重指数、肿瘤位置和大小、TNM分期和DNA微卫星不稳定性高的情况相当。纹身组(107 人)和对照组(143 人)在淋巴结切除率方面没有差异(78% 对 79%,P=0.40)。对所有已知的影响大肠标本淋巴结取材的因素进行了专门评估。对直肠癌和结肠癌进行了综合分析和单独分析。对接受结肠切除术的患者进行的全面调整逻辑回归分析表明,右半结肠切除术(OR 4.72;CI95% 1.09-20.36)是唯一与淋巴结充分切除相关的因素。通过逻辑回归分析发现,术前为标记肿瘤部位而进行的墨水纹身与结肠直肠切除术后淋巴结的充分切除之间没有关联:本研究表明,术前利用纹身标记肿瘤部位并不能提高淋巴结切除率和大肠癌标本的淋巴结产量。因此,需要进一步研究确定术前结肠镜纹身标记肿瘤部位是否能完善分期。
{"title":"Preoperative endoscopic tattooing to mark the tumour site does not improve lymph node retrieval in colorectal cancer: a retrospective cohort study.","authors":"Carlo V Feo, Mattia Portinari, Michele Zuolo, Simone Targa, Vincenzo G Matarese, Roberta Gafà, Elena Forini, Giovanni Lanza","doi":"10.1186/s12952-015-0027-7","DOIUrl":"10.1186/s12952-015-0027-7","url":null,"abstract":"<p><strong>Background: </strong>A direct correlation between number of lymph nodes retrieved and evaluated after a colectomy for colorectal cancer and survival of the patient has been reported, and consensus guidelines recommend to assess at least 12 lymph nodes for adequate staging. Many factors (i.e., patients' and tumour characteristics, surgeon, and pathologist) may influence the evaluation of the presence of neoplastic disease in lymph nodes as well as the total number of lymph nodes examined. Preoperative endoscopic tattooing to mark the site of the tumour has recently been suggested to facilitate the retrieval of lymph nodes in colorectal specimens. The aim of this study was to investigate its association with adequate lymphadenectomy (≥12 nodes) after colorectal resection for cancer.</p><p><strong>Results: </strong>All patients undergoing elective colorectal resection for cancer between 2009 and 2011 at the S. Anna University Hospital in Ferrara, Italy (N = 250) were retrospectively divided into two cohorts according to whether ink tattooing to mark the tumour site was performed during preoperative colonoscopy. The two cohorts were comparable regarding age, gender, body mass index, tumour location and size, TNM staging, and DNA microsatellite instability-high status. No difference between the tattoo (N = 107) and control (N = 143) groups could be detected in the rate of adequate lymphadenectomies performed (78% vs. 79%, p = 0.40). All factors known to influence lymph nodes retrieval from colorectal specimen were specifically evaluated. Rectal and colonic cancers were analysed together and separately. Full adjusted logistic regression analysis in patients who underwent colonic resection showed that right hemicolectomy (OR 4.72; CI95% 1.09-20.36) was the only factor associated to adequate lymphadenectomy. No association between ink tattooing performed preoperatively to mark the site of the tumour and adequate lymphadenectomy after colorectal resection was found with logistic regression analysis.</p><p><strong>Conclusion: </strong>This study shows that preoperative ink tattooing utilized to mark the site of the tumour does not improve adequate lymphadenectomy and lymph nodes yield from colorectal cancer specimens. Further studies are therefore needed to determine if preoperative colonoscopic tattooing to mark the tumour site can refine staging.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33279232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-04-30DOI: 10.1186/s12952-015-0028-6
Bruno Heleno, Volkert Siersma, John Brodersen
Background: There is wide variation in the psychosocial response to false-positive mammography. We aimed to assess whether women having to wait longer to exclude cancer had increased psychosocial consequences that persisted after cancer was ruled out.
Findings: We selected women with false-positive mammography (n = 272), screened for breast cancer in Copenhagen and Funen (Denmark) over a 1-year period. We measured psychosocial consequences immediately before women attended their recall visit and 1, 6, 18 and 36 months after women received their final diagnosis. After women were told that cancer had been ruled out, adverse psychosocial consequences decreased with time. We found no statistically significant differences between women who had cancer ruled out immediately at the recall visit (waiting time of 0) and women who had to wait longer before cancer was ruled out (waiting times 1-30, 30-120 and > 120 days), when psychosocial consequences were measured via a condition-specific questionnaire (Consequences of Screening in Breast Cancer) at 5 time points (0, 1, 6, 18 and 36 months after cancer exclusion).
Conclusion: We did not confirm that waiting time was associated with worse long-term psychosocial consequences but type II error (failure to detect a true difference) might be a plausible explanation for our results.
{"title":"Waiting time and the psychosocial consequences of false-positive mammography: cohort study.","authors":"Bruno Heleno, Volkert Siersma, John Brodersen","doi":"10.1186/s12952-015-0028-6","DOIUrl":"10.1186/s12952-015-0028-6","url":null,"abstract":"<p><strong>Background: </strong>There is wide variation in the psychosocial response to false-positive mammography. We aimed to assess whether women having to wait longer to exclude cancer had increased psychosocial consequences that persisted after cancer was ruled out.</p><p><strong>Findings: </strong>We selected women with false-positive mammography (n = 272), screened for breast cancer in Copenhagen and Funen (Denmark) over a 1-year period. We measured psychosocial consequences immediately before women attended their recall visit and 1, 6, 18 and 36 months after women received their final diagnosis. After women were told that cancer had been ruled out, adverse psychosocial consequences decreased with time. We found no statistically significant differences between women who had cancer ruled out immediately at the recall visit (waiting time of 0) and women who had to wait longer before cancer was ruled out (waiting times 1-30, 30-120 and > 120 days), when psychosocial consequences were measured via a condition-specific questionnaire (Consequences of Screening in Breast Cancer) at 5 time points (0, 1, 6, 18 and 36 months after cancer exclusion).</p><p><strong>Conclusion: </strong>We did not confirm that waiting time was associated with worse long-term psychosocial consequences but type II error (failure to detect a true difference) might be a plausible explanation for our results.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33260602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-03-18DOI: 10.1186/s12952-015-0026-8
Neda M Bogari, Azza M Abdel-Latif, Maha A Hassan, Abeer Ramadan, Ahmed Fawzy
Background: Several environmental and genetic factors are associated with high levels of lipids in obese patients. Apolipoprotein B (ApoB) is the major protein component of low-density lipoproteins (LDL), very-low density lipoproteins (VLDL) and chylomicrons and plays a central role in lipid metabolism. Several apoB restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels and obesity. To date, no data are available on the relationship between XbaI polymorphism and lipid levels in Egyptian populations. Following clinical profiling, 178 obese (body mass index [BMI] >25 kg/m(2)) and 178 age-matched non-obese (BMI ≤ 25 kg/m(2)) subjects were included in this case-control study. All samples were analysed for total cholesterol, triglycerides and HDL-cholesterol. Genetic analysis of apoB XbaI (X) was performed using Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). The aim of this study was to assess the association of apoB XbaI gene polymorphism (X) and lipid profiles in obese and non-obese Egyptian populations.
Results: Obese subjects demonstrated significantly higher values of waist-to-hip ratio, blood pressure, and total lipid. However, in our sample we did not find significant differences in apoB XbaI gene polymorphism (X) genotype or allele frequencies. Moreover, none of the studied lipid parameters showed any association with the gene polymorphism.
Conclusion: This study reveals no significant association of apoB XbaI gene polymorphism (X) with obesity or lipid profiles in an Egyptian population.
{"title":"No association of apolipoprotein B gene polymorphism and blood lipids in obese Egyptian subjects.","authors":"Neda M Bogari, Azza M Abdel-Latif, Maha A Hassan, Abeer Ramadan, Ahmed Fawzy","doi":"10.1186/s12952-015-0026-8","DOIUrl":"10.1186/s12952-015-0026-8","url":null,"abstract":"<p><strong>Background: </strong>Several environmental and genetic factors are associated with high levels of lipids in obese patients. Apolipoprotein B (ApoB) is the major protein component of low-density lipoproteins (LDL), very-low density lipoproteins (VLDL) and chylomicrons and plays a central role in lipid metabolism. Several apoB restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels and obesity. To date, no data are available on the relationship between XbaI polymorphism and lipid levels in Egyptian populations. Following clinical profiling, 178 obese (body mass index [BMI] >25 kg/m(2)) and 178 age-matched non-obese (BMI ≤ 25 kg/m(2)) subjects were included in this case-control study. All samples were analysed for total cholesterol, triglycerides and HDL-cholesterol. Genetic analysis of apoB XbaI (X) was performed using Polymerase Chain Reaction-Restriction Fragment Length polymorphism (PCR-RFLP). The aim of this study was to assess the association of apoB XbaI gene polymorphism (X) and lipid profiles in obese and non-obese Egyptian populations.</p><p><strong>Results: </strong>Obese subjects demonstrated significantly higher values of waist-to-hip ratio, blood pressure, and total lipid. However, in our sample we did not find significant differences in apoB XbaI gene polymorphism (X) genotype or allele frequencies. Moreover, none of the studied lipid parameters showed any association with the gene polymorphism.</p><p><strong>Conclusion: </strong>This study reveals no significant association of apoB XbaI gene polymorphism (X) with obesity or lipid profiles in an Egyptian population.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4389411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33232226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-03-06DOI: 10.1186/s12952-015-0025-9
B. Olsen, B. Brachvogel
{"title":"Thanks to all those who reviewed for Journal of Negative Results in Biomedicine in 2014","authors":"B. Olsen, B. Brachvogel","doi":"10.1186/s12952-015-0025-9","DOIUrl":"https://doi.org/10.1186/s12952-015-0025-9","url":null,"abstract":"","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-015-0025-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65694595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-03-05DOI: 10.1186/s12952-015-0023-y
Ingrid Eitzen, Linda Fernandes, Lars Nordsletten, May Arna Risberg
Background: It is unknown whether gait biomechanics in hip osteoarthritis patients with mild to moderate symptoms change following exercise therapy interventions. The aim of the present study was to compare stance phase gait characteristics in hip osteoarthritis patients with mild to moderate symptoms participating in a randomized trial with two different interventions; patient education only or patient education followed by a 12-week supervised exercise therapy program.
Results: The study was conducted as a secondary analysis of a single-blinded randomized controlled trial. Patients aged 40 to 80 years, with hip osteoarthritis verified from self-reported pain and radiographic changes, were included. The final material comprised 23 patients (10 males/13 females, mean (SD) age 58.2 (10.02) years) in the patient education only group, and 22 patients (9 males/13 females, mean (SD) age 60.2 (9.49) years) in the patient education + exercise therapy group. Three-dimensional gait analysis was conducted at baseline and at four month follow-up. Sagittal and frontal plane joint angle displacement and external joint moments of the hip, knee and ankle were compared from a one-way analysis of covariance between the groups at follow-up, with baseline values as covariates (p < 0.05). No group differences were observed at the four-month follow-up in gait velocity, joint angle displacement, or moments. As the compliance in the exercise therapy group was inadequate, we calculated possible associations between the number of completed exercise sessions and change in each of the kinematic or kinetic variables. Associations were weak to neglible. Thus, the negative findings in this study cannot be explained from inadequate compliance alone, but most likely also suggest the exercise therapy program itself to be insufficient to engender gait alterations.
Conclusions: Adding a 12-week supervised exercise therapy program to patient education did not induce changes in our selected biomechanical variables during the stance phase of gait, even when adjusting for poor compliance. Thus, we did not find evidence to support our exercise therapy program to be an efficacious intervention to induce gait alterations in this population of hip osteoarthritis patients.
Trial registration: NCT00319423 at ClinicalTrials.gov (registration date 2006-04-26).
{"title":"No effects of a 12-week supervised exercise therapy program on gait in patients with mild to moderate osteoarthritis: a secondary analysis of a randomized trial.","authors":"Ingrid Eitzen, Linda Fernandes, Lars Nordsletten, May Arna Risberg","doi":"10.1186/s12952-015-0023-y","DOIUrl":"https://doi.org/10.1186/s12952-015-0023-y","url":null,"abstract":"<p><strong>Background: </strong>It is unknown whether gait biomechanics in hip osteoarthritis patients with mild to moderate symptoms change following exercise therapy interventions. The aim of the present study was to compare stance phase gait characteristics in hip osteoarthritis patients with mild to moderate symptoms participating in a randomized trial with two different interventions; patient education only or patient education followed by a 12-week supervised exercise therapy program.</p><p><strong>Results: </strong>The study was conducted as a secondary analysis of a single-blinded randomized controlled trial. Patients aged 40 to 80 years, with hip osteoarthritis verified from self-reported pain and radiographic changes, were included. The final material comprised 23 patients (10 males/13 females, mean (SD) age 58.2 (10.02) years) in the patient education only group, and 22 patients (9 males/13 females, mean (SD) age 60.2 (9.49) years) in the patient education + exercise therapy group. Three-dimensional gait analysis was conducted at baseline and at four month follow-up. Sagittal and frontal plane joint angle displacement and external joint moments of the hip, knee and ankle were compared from a one-way analysis of covariance between the groups at follow-up, with baseline values as covariates (p < 0.05). No group differences were observed at the four-month follow-up in gait velocity, joint angle displacement, or moments. As the compliance in the exercise therapy group was inadequate, we calculated possible associations between the number of completed exercise sessions and change in each of the kinematic or kinetic variables. Associations were weak to neglible. Thus, the negative findings in this study cannot be explained from inadequate compliance alone, but most likely also suggest the exercise therapy program itself to be insufficient to engender gait alterations.</p><p><strong>Conclusions: </strong>Adding a 12-week supervised exercise therapy program to patient education did not induce changes in our selected biomechanical variables during the stance phase of gait, even when adjusting for poor compliance. Thus, we did not find evidence to support our exercise therapy program to be an efficacious intervention to induce gait alterations in this population of hip osteoarthritis patients.</p><p><strong>Trial registration: </strong>NCT00319423 at ClinicalTrials.gov (registration date 2006-04-26).</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-015-0023-y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33227378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-02-13DOI: 10.1186/s12952-015-0024-x
N Susantha Chandrasekera, Torey Alling, Mai Bailey, Aaron Korkegian, James Ahn, Yulia Ovechkina, Joshua Odingo, Tanya Parish
Background: Tuberculosis (TB) caused by Mycobacterium tuberculosis is the leading cause of death from a bacterial infection. The 4-aminopiperidine (PIP) series has been reported as having anti-bacterial activity against M. tuberculosis. We explored this series for its potential to inhibit aerobic growth of M. tuberculosis. We examined substitution at the N-1 position and C-4 position of the piperidine and modifications of the piperidine moiety systematically to delineate structure-activity relationships influencing potency. Compounds were tested for growth-inhibitory activity against virulent M. tuberculosis. A selected set of compounds were also tested for its activity against Staphylococcus aureus.
Results: The compound with a norbornenylmethyl substituent at the N-1 position and N-benzyl-N-phenethylamine at the C-4 position of the piperidine (1) was the only active compound with a minimum inhibitory concentration (MIC) of 10 μM against M. tuberculosis. Compounds were not active against S. aureus.
Conclusions: We were unable to derive any other analogs with MIC < 20 μM against M. tuberculosis. Therefore we conclude that the lack of activity is a liability in this series precluding it from further development.
背景:结核分枝杆菌引起的结核病(TB)是细菌感染导致死亡的主要原因。据报道,4-氨基哌啶(PIP)系列对结核分枝杆菌具有抗菌活性。我们探索了这个系列的潜力,以抑制结核分枝杆菌的有氧生长。我们系统地研究了哌啶在N-1位和C-4位的取代以及哌啶部分的修饰,以描述影响药效的构效关系。测定了化合物对致病性结核分枝杆菌的生长抑制活性。一组选定的化合物也测试了其对金黄色葡萄球菌的活性。结果:在哌替啶(1)的N-1位含有降冰片甲基取代基,C-4位含有n -苄基- n -苯乙胺的化合物是唯一对结核分枝杆菌具有10 μM最小抑制浓度(MIC)的活性化合物。化合物对金黄色葡萄球菌无活性。结论:我们无法获得任何其他MIC < 20 μM的抗结核分枝杆菌类似物。因此,我们得出结论,缺乏活动是该系列的一个不利因素,使其无法进一步发展。
{"title":"The 4-aminopiperidine series has limited anti-tubercular and anti-staphylococcus aureus activity.","authors":"N Susantha Chandrasekera, Torey Alling, Mai Bailey, Aaron Korkegian, James Ahn, Yulia Ovechkina, Joshua Odingo, Tanya Parish","doi":"10.1186/s12952-015-0024-x","DOIUrl":"https://doi.org/10.1186/s12952-015-0024-x","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) caused by Mycobacterium tuberculosis is the leading cause of death from a bacterial infection. The 4-aminopiperidine (PIP) series has been reported as having anti-bacterial activity against M. tuberculosis. We explored this series for its potential to inhibit aerobic growth of M. tuberculosis. We examined substitution at the N-1 position and C-4 position of the piperidine and modifications of the piperidine moiety systematically to delineate structure-activity relationships influencing potency. Compounds were tested for growth-inhibitory activity against virulent M. tuberculosis. A selected set of compounds were also tested for its activity against Staphylococcus aureus.</p><p><strong>Results: </strong>The compound with a norbornenylmethyl substituent at the N-1 position and N-benzyl-N-phenethylamine at the C-4 position of the piperidine (1) was the only active compound with a minimum inhibitory concentration (MIC) of 10 μM against M. tuberculosis. Compounds were not active against S. aureus.</p><p><strong>Conclusions: </strong>We were unable to derive any other analogs with MIC < 20 μM against M. tuberculosis. Therefore we conclude that the lack of activity is a liability in this series precluding it from further development.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-015-0024-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33104428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-02-04DOI: 10.1186/s12952-014-0022-4
Xiaoyan Mao, Marc R Del Bigio
Background: Prior work showed that whole blood, plasma, and serum injections are damaging to the neonatal rodent brain in a model of intracerebral/periventricular hemorrhage. Thrombin alone is also damaging. In adult animal models of hemorrhagic stroke, the protease-activated (thrombin) receptor PAR1 mediates some of the brain damage. We hypothesized that PAR1 interference will reduce the adverse effects of blood products on immature rodent brain and cells.
Results: Cultured oligodendrocyte precursor cells from rats and mice were exposed to blood plasma with and without the PAR1 antagonists SCH-79797 or BMS-200261. In concentrations previously shown to have activity on brain cells, neither drug showed evidence of protection against the toxicity of blood plasma. Newborn mice (wild type, heterozygous, and PAR1 knockout) were subjected to intracerebral injection of autologous whole blood into the periventricular region of the frontal lobe. Cell proliferation, measured by Ki67 immunoreactivity in the subventricular zone, was suppressed at 1 and 2 days, and was not normalized in the knockout mice. Cell apoptosis, measured by activated caspase 3 immunoreactivity, was not apparent in the subventricular zone. Increased apoptosis in periventricular striatal cells was not normalized in the knockout mice.
Conclusion: Interference with the thrombin-PAR1 system does not reduce the adverse effects of blood on germinal cells of the immature rodent brain. PAR1 interference is unlikely to be a useful treatment for reducing the brain damage that accompanies periventricular (germinal matrix) hemorrhage, a common complication of premature birth.
{"title":"Interference with protease-activated receptor 1 does not reduce damage to subventricular zone cells of immature rodent brain following exposure to blood or blood plasma.","authors":"Xiaoyan Mao, Marc R Del Bigio","doi":"10.1186/s12952-014-0022-4","DOIUrl":"10.1186/s12952-014-0022-4","url":null,"abstract":"<p><strong>Background: </strong>Prior work showed that whole blood, plasma, and serum injections are damaging to the neonatal rodent brain in a model of intracerebral/periventricular hemorrhage. Thrombin alone is also damaging. In adult animal models of hemorrhagic stroke, the protease-activated (thrombin) receptor PAR1 mediates some of the brain damage. We hypothesized that PAR1 interference will reduce the adverse effects of blood products on immature rodent brain and cells.</p><p><strong>Results: </strong>Cultured oligodendrocyte precursor cells from rats and mice were exposed to blood plasma with and without the PAR1 antagonists SCH-79797 or BMS-200261. In concentrations previously shown to have activity on brain cells, neither drug showed evidence of protection against the toxicity of blood plasma. Newborn mice (wild type, heterozygous, and PAR1 knockout) were subjected to intracerebral injection of autologous whole blood into the periventricular region of the frontal lobe. Cell proliferation, measured by Ki67 immunoreactivity in the subventricular zone, was suppressed at 1 and 2 days, and was not normalized in the knockout mice. Cell apoptosis, measured by activated caspase 3 immunoreactivity, was not apparent in the subventricular zone. Increased apoptosis in periventricular striatal cells was not normalized in the knockout mice.</p><p><strong>Conclusion: </strong>Interference with the thrombin-PAR1 system does not reduce the adverse effects of blood on germinal cells of the immature rodent brain. PAR1 interference is unlikely to be a useful treatment for reducing the brain damage that accompanies periventricular (germinal matrix) hemorrhage, a common complication of premature birth.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4327806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33027744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-14DOI: 10.1186/s12952-014-0021-5
Francesca Ravanetti, Carlo Galli, Edoardo Manfredi, Anna Maria Cantoni, Edoardo Scarpa, Guido Maria Macaluso, Antonio Cacchioli
Background: Osteochondral defects significantly affect patients' quality of life and represent challenging tissue lesions, because of the poor regenerative capacity of cartilage. Tissue engineering has long sought to promote cartilage repair, by employing artificial scaffolds to enhance cell capacity to deposit new cartilage. An ideal biomaterial should closely mimic the natural environment of the tissue, to promote scaffold colonization, cell differentiation and the maintenance of a differentiated cellular phenotype. The present study evaluated chitosan scaffolds enriched with D-(+) raffinose in osteochondral defects in rabbits. Cartilage defects were created in distal femurs, both on the condyle and on the trochlea, and were left untreated or received a chitosan scaffold. The animals were sacrificed after 2 or 4 weeks, and samples were analysed microscopically.
Results: The retrieved implants were surrounded by a fibrous capsule and contained a noticeable inflammatory infiltrate. No hyaline cartilage was formed in the defects. Although defect closure reached approximately 100% in the control group after 4 weeks, defects did not completely heal when filled with chitosan. In these samples, the lesion contained granulation tissue at 2 weeks, which was then replaced by fibrous connective tissue by week 4. Noteworthy, chitosan never appeared to be integrated in the surrounding cartilage.
Conclusions: In conclusion, the present study highlights the limits of D-(+) raffinose-enriched chitosan for cartilage regeneration and offers useful information for further development of this material for tissue repair.
{"title":"Chitosan-based scaffold modified with D-(+) raffinose for cartilage repair: an in vivo study.","authors":"Francesca Ravanetti, Carlo Galli, Edoardo Manfredi, Anna Maria Cantoni, Edoardo Scarpa, Guido Maria Macaluso, Antonio Cacchioli","doi":"10.1186/s12952-014-0021-5","DOIUrl":"https://doi.org/10.1186/s12952-014-0021-5","url":null,"abstract":"<p><strong>Background: </strong>Osteochondral defects significantly affect patients' quality of life and represent challenging tissue lesions, because of the poor regenerative capacity of cartilage. Tissue engineering has long sought to promote cartilage repair, by employing artificial scaffolds to enhance cell capacity to deposit new cartilage. An ideal biomaterial should closely mimic the natural environment of the tissue, to promote scaffold colonization, cell differentiation and the maintenance of a differentiated cellular phenotype. The present study evaluated chitosan scaffolds enriched with D-(+) raffinose in osteochondral defects in rabbits. Cartilage defects were created in distal femurs, both on the condyle and on the trochlea, and were left untreated or received a chitosan scaffold. The animals were sacrificed after 2 or 4 weeks, and samples were analysed microscopically.</p><p><strong>Results: </strong>The retrieved implants were surrounded by a fibrous capsule and contained a noticeable inflammatory infiltrate. No hyaline cartilage was formed in the defects. Although defect closure reached approximately 100% in the control group after 4 weeks, defects did not completely heal when filled with chitosan. In these samples, the lesion contained granulation tissue at 2 weeks, which was then replaced by fibrous connective tissue by week 4. Noteworthy, chitosan never appeared to be integrated in the surrounding cartilage.</p><p><strong>Conclusions: </strong>In conclusion, the present study highlights the limits of D-(+) raffinose-enriched chitosan for cartilage regeneration and offers useful information for further development of this material for tissue repair.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-014-0021-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32973019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2015-01-08DOI: 10.1186/s12952-014-0020-6
Zaiharina Mohamad Zamberi, Zuraihan Zakaria, Abu Thalhah Abdul Aziz, Benedict Sim Lim Heng, Masliza Zaid, Christopher Lee Kwok Chong, Fadzilah Mohd Noor, Sazaly Abu Bakar, Hoh Boon Peng
Background: Dengue is a major public health problem in many tropical and sub-tropical countries. Vascular leakage and shock are identified as the major causes of deaths in patients with severe dengue. Studies have suggested the potential role of Fc gamma receptors I (FcγRI) in the pathogenesis of dengue. We hypothesized that the circulating level of Fcγ receptor I could potentially be used as an indicator in assisting early diagnosis of severe dengue.
Results: A selected cohort of 66 dengue patients including 42 dengue with signs of vascular leakage, and 24 dengue without signs of vascular leakage were identified and were afterwards referred to as 'cases' and 'controls' respectively. Thirty seven normal healthy controls were also recruited in this study. The circulating level of FcγRI was quantified from the serum using enzyme-link immunosorbent assay (ELISA). The levels of FcγRI in both groups of patients with and without vascular leakage were found to be significantly higher than the normal healthy controls (P < 0.001). However, there was no significant difference found between patients with vascular leakage and those without vascular leakage (p = 0.777).
Conclusion: We suggest that FcγRI is not associated with the vascular leakage in dengue. However, further studies are necessary to delineate the role of FcγRI in antibody-dependent enhancement (ADE) mechanism.
{"title":"The high-affinity human IgG receptor Fc gamma receptor I (FcγRI) is not associated with vascular leakage of dengue.","authors":"Zaiharina Mohamad Zamberi, Zuraihan Zakaria, Abu Thalhah Abdul Aziz, Benedict Sim Lim Heng, Masliza Zaid, Christopher Lee Kwok Chong, Fadzilah Mohd Noor, Sazaly Abu Bakar, Hoh Boon Peng","doi":"10.1186/s12952-014-0020-6","DOIUrl":"https://doi.org/10.1186/s12952-014-0020-6","url":null,"abstract":"<p><strong>Background: </strong>Dengue is a major public health problem in many tropical and sub-tropical countries. Vascular leakage and shock are identified as the major causes of deaths in patients with severe dengue. Studies have suggested the potential role of Fc gamma receptors I (FcγRI) in the pathogenesis of dengue. We hypothesized that the circulating level of Fcγ receptor I could potentially be used as an indicator in assisting early diagnosis of severe dengue.</p><p><strong>Results: </strong>A selected cohort of 66 dengue patients including 42 dengue with signs of vascular leakage, and 24 dengue without signs of vascular leakage were identified and were afterwards referred to as 'cases' and 'controls' respectively. Thirty seven normal healthy controls were also recruited in this study. The circulating level of FcγRI was quantified from the serum using enzyme-link immunosorbent assay (ELISA). The levels of FcγRI in both groups of patients with and without vascular leakage were found to be significantly higher than the normal healthy controls (P < 0.001). However, there was no significant difference found between patients with vascular leakage and those without vascular leakage (p = 0.777).</p><p><strong>Conclusion: </strong>We suggest that FcγRI is not associated with the vascular leakage in dengue. However, further studies are necessary to delineate the role of FcγRI in antibody-dependent enhancement (ADE) mechanism.</p>","PeriodicalId":73849,"journal":{"name":"Journal of negative results in biomedicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12952-014-0020-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32956763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}