Pub Date : 2017-01-01DOI: 10.4172/CLINICAL-INVESTIGATION.1000129
R. Bhardwaj, R. Deshmukh
Neurotrophins play a major role in adult neuronal survival, maintenance and regeneration. Alterations in their levels have been implicated in various neurodegenerative disorders, including Parkinson’s disease (PD). It has been reported that, the pathophysiology of PD progress is essentially depends on various striatal signaling cascade, which consists handful of neurotrophic factors namely, cerebral dopamine neurotrophic factor (CDNF), glial derived neurotrophic factor (GDNF), mesencephalic astrocyte-derived neurotrophic factor (MANF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF). Although, the exact pathophysiology of PD is remained elusive however, the loss of dopaminergic neurons and dopamine deficiency has considered as a major consequence for the movement disability as seen in PD. It has been proposed that loss of dopaminergic neurons in PD may be conducted by inadequate neurotrophic activity which leads to neuronal apoptosis. In addition, stimulation of neurotrophic factors in the striatal brain region has been reported to be beneficial in experimental models of PD. In the current review we have detailed out the neurotrophic factors and their role in pathogenesis of Parkinson’s disease.
{"title":"Neurotrophic factors and Parkinson's disease","authors":"R. Bhardwaj, R. Deshmukh","doi":"10.4172/CLINICAL-INVESTIGATION.1000129","DOIUrl":"https://doi.org/10.4172/CLINICAL-INVESTIGATION.1000129","url":null,"abstract":"Neurotrophins play a major role in adult neuronal survival, maintenance and regeneration. Alterations in their levels have been implicated in various neurodegenerative disorders, including Parkinson’s disease (PD). It has been reported that, the pathophysiology of PD progress is essentially depends on various striatal signaling cascade, which consists handful of neurotrophic factors namely, cerebral dopamine neurotrophic factor (CDNF), glial derived neurotrophic factor (GDNF), mesencephalic astrocyte-derived neurotrophic factor (MANF), brain derived neurotrophic factor (BDNF), nerve growth factor (NGF). Although, the exact pathophysiology of PD is remained elusive however, the loss of dopaminergic neurons and dopamine deficiency has considered as a major consequence for the movement disability as seen in PD. It has been proposed that loss of dopaminergic neurons in PD may be conducted by inadequate neurotrophic activity which leads to neuronal apoptosis. In addition, stimulation of neurotrophic factors in the striatal brain region has been reported to be beneficial in experimental models of PD. In the current review we have detailed out the neurotrophic factors and their role in pathogenesis of Parkinson’s disease.","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"20 1","pages":"53-62"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83698280","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 : 2017-01-01DOI: 10.4172/CLINICAL-INVESTIGATION.1000118
P. Smid, M. Komzák, R. Hart, L. Paša
Background: The objective of the study was to demonstrate the effect of concentrated bone marrow stem cells (MSCs) to the healing of sutured tendon of the supraspinatus muscle in comparison to the same procedure performed without MSCs. We have postulated the hypothesis that MSCs enhance the healing of the sutured supraspinatus tendon to its humeral footprint. Methods and findings: None of the patients had to be excluded from our prospective randomized study. 50 patients met the indication criteria for isolated supraspinatus surgery. 25 patients (Group I) received MSCs into the supraspinatus footprint. 25 patients (Group II) was treated without the use of MSCs. Patients were examined pre-operatively, 6, 12 and 24 months after the surgery and assessment included physical examination, visual analogue scale (VAS), ASES (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form) and Constant score. Patients underwent MRI 2 years postoperatively. Findings were compared with the preoperative results. We have found no statistically significant differences between both groups pre-operatively. After a 24-month follow-up period there were significant differences observed in all clinical outcomes. When compared results between both groups two years postoperatively, p-value (p=0.05) for the VAS score was 0.0176 and for the Constant score 0.0355. The only statistically non-significant was p-value for the ASES score comparing results from both groups at two years follow-up (p=0.085). The MRI findings at 2 years showed fully healed tissue of the rotator cuff tendon in 17 patients in the Group I, but only in 9 patients in the Group II. Conclusions: We have accepted the hypothesis that MSCs enhance the healing of the sutured supraspinatus tendon to its humeral footprint.
{"title":"Mesenchymal stem cells in the reconstruction surgery of the supraspinatus muscle lesions","authors":"P. Smid, M. Komzák, R. Hart, L. Paša","doi":"10.4172/CLINICAL-INVESTIGATION.1000118","DOIUrl":"https://doi.org/10.4172/CLINICAL-INVESTIGATION.1000118","url":null,"abstract":"Background: The objective of the study was to demonstrate the effect of concentrated bone marrow stem cells (MSCs) to the healing of sutured tendon of the supraspinatus muscle in comparison to the same procedure performed without MSCs. We have postulated the hypothesis that MSCs enhance the healing of the sutured supraspinatus tendon to its humeral footprint. Methods and findings: None of the patients had to be excluded from our prospective randomized study. 50 patients met the indication criteria for isolated supraspinatus surgery. 25 patients (Group I) received MSCs into the supraspinatus footprint. 25 patients (Group II) was treated without the use of MSCs. Patients were examined pre-operatively, 6, 12 and 24 months after the surgery and assessment included physical examination, visual analogue scale (VAS), ASES (American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form) and Constant score. Patients underwent MRI 2 years postoperatively. Findings were compared with the preoperative results. We have found no statistically significant differences between both groups pre-operatively. After a 24-month follow-up period there were significant differences observed in all clinical outcomes. When compared results between both groups two years postoperatively, p-value (p=0.05) for the VAS score was 0.0176 and for the Constant score 0.0355. The only statistically non-significant was p-value for the ASES score comparing results from both groups at two years follow-up (p=0.085). The MRI findings at 2 years showed fully healed tissue of the rotator cuff tendon in 17 patients in the Group I, but only in 9 patients in the Group II. Conclusions: We have accepted the hypothesis that MSCs enhance the healing of the sutured supraspinatus tendon to its humeral footprint.","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"106 1","pages":"103-110"},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73544973","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 : 2016-12-15DOI: 10.1158/1538-7445.PANCA16-B89
S. Shahda, M. House, C. Schmidt, A. Nakeeb, A. Sehdev, Jingmei Lin, H. Cramer, Y. Tong, J. Flynn, N. Zyromski, B. O'Neil
{"title":"Abstract B89: Neoadjuvant FOLFIRINOX in patients with resectable pancreatic cancer","authors":"S. Shahda, M. House, C. Schmidt, A. Nakeeb, A. Sehdev, Jingmei Lin, H. Cramer, Y. Tong, J. Flynn, N. Zyromski, B. O'Neil","doi":"10.1158/1538-7445.PANCA16-B89","DOIUrl":"https://doi.org/10.1158/1538-7445.PANCA16-B89","url":null,"abstract":"","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86733987","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 : 2016-12-15DOI: 10.1158/1538-7445.panca16-b86
S. Kalloger, J. Karasinska, H. Wong, D. Renouf, D. Schaeffer
{"title":"Abstract B86: Novel assessment of SPARC expression by hierarchical clustering in pancreatic ductal adenocarcinoma shows distinct prognostic and predictive groups","authors":"S. Kalloger, J. Karasinska, H. Wong, D. Renouf, D. Schaeffer","doi":"10.1158/1538-7445.panca16-b86","DOIUrl":"https://doi.org/10.1158/1538-7445.panca16-b86","url":null,"abstract":"","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"155 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81790014","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 : 2016-12-15DOI: 10.1158/1538-7445.panca16-b16
S. Kugel, C. Sebastián, Julien Fitamant, K. Ross, Supriya K. Saha, Esha Jain, A. Gladden, Kshitij S Arora, Y. Kato, M. Rivera, Sridhar Ramaswamy, R. Sadreyev, A. Goren, V. Deshpande, N. Bardeesy, R. Mostoslavsky
{"title":"Abstract B16: Loss of SIRT6 reactivates the RNA-binding protein Lin28b to drive pancreatic cancer","authors":"S. Kugel, C. Sebastián, Julien Fitamant, K. Ross, Supriya K. Saha, Esha Jain, A. Gladden, Kshitij S Arora, Y. Kato, M. Rivera, Sridhar Ramaswamy, R. Sadreyev, A. Goren, V. Deshpande, N. Bardeesy, R. Mostoslavsky","doi":"10.1158/1538-7445.panca16-b16","DOIUrl":"https://doi.org/10.1158/1538-7445.panca16-b16","url":null,"abstract":"","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85830964","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}
Survival analysis is often performed using the Cox proportional hazards model. Parametric models are useful in several applications, including health economic evaluation, cancer surveillance and event prediction. Flexible parametric models extend standard parametric models (e.g., Weibull) to increase the flexibility of the shape of the hazard function. We present a new SAS® macro for implementing flexible parametric models with a similar functionality to that of Stata®, with examples using data from cancer surveillance and clinical trials. Results from SAS were identical with similar computational time to Stata. The flexible parametric approach to modeling survival data is shown to be superior to standard parametric methods. This SAS macro will facilitate an increase in the use of flexible parametric models.
{"title":"A new SAS ® macro for flexible parametric survival modeling: applications to clinical trials and surveillance data","authors":"R. Dewar, I. Khan","doi":"10.4155/CLI.15.54","DOIUrl":"https://doi.org/10.4155/CLI.15.54","url":null,"abstract":"Survival analysis is often performed using the Cox proportional hazards model. Parametric models are useful in several applications, including health economic evaluation, cancer surveillance and event prediction. Flexible parametric models extend standard parametric models (e.g., Weibull) to increase the flexibility of the shape of the hazard function. We present a new SAS® macro for implementing flexible parametric models with a similar functionality to that of Stata®, with examples using data from cancer surveillance and clinical trials. Results from SAS were identical with similar computational time to Stata. The flexible parametric approach to modeling survival data is shown to be superior to standard parametric methods. This SAS macro will facilitate an increase in the use of flexible parametric models.","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"2 1","pages":"855-866"},"PeriodicalIF":0.0,"publicationDate":"2015-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81783473","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}
In many respects, clinical trials can be seen as an art as well as a science, in that there is ample discretion for investigators to select research methods reflecting their own individual preferences. In fact, new research methods are developed on a fairly regular basis, not all of them improvements over existing methods. But the opposite trend also remains in effect, as researchers often follow established precedent, rather than thinking through the issues relevant to the current trial so as to come up with the research methods that are optimal in this case. These two forces pulling in opposite directions, individuality and inertia, compete in many aspects of clinical research, including the specific methods of randomization. New randomization methods are constantly proposed, while at the same time more and more researchers seem to be using the established standards of permuted blocks randomization or minimization (which, in its most extreme form, is not even true randomization at all). A comprehensive ...
{"title":"A review of randomization methods in clinical trials","authors":"V. Berger, Olga Antsygina","doi":"10.4155/CLI.15.53","DOIUrl":"https://doi.org/10.4155/CLI.15.53","url":null,"abstract":"In many respects, clinical trials can be seen as an art as well as a science, in that there is ample discretion for investigators to select research methods reflecting their own individual preferences. In fact, new research methods are developed on a fairly regular basis, not all of them improvements over existing methods. But the opposite trend also remains in effect, as researchers often follow established precedent, rather than thinking through the issues relevant to the current trial so as to come up with the research methods that are optimal in this case. These two forces pulling in opposite directions, individuality and inertia, compete in many aspects of clinical research, including the specific methods of randomization. New randomization methods are constantly proposed, while at the same time more and more researchers seem to be using the established standards of permuted blocks randomization or minimization (which, in its most extreme form, is not even true randomization at all). A comprehensive ...","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"42 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2015-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84053367","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}
Conducting prospective studies in hospices can be difficult. We conducted a systematic review to find randomized trials that have been conducted in US hospices and to review them for quality and potential bias. Ten studies met our inclusion criteria; a wide variety of outcomes were studied. Most of the studies had at least moderate risk of bias due either to incomplete reporting of methods or the inability to blind investigators. To provide better evidence-based hospice care, more well-designed trials that are consistently reported are needed.
{"title":"Randomized clinical trials in US hospices: challenges and the current state of the art","authors":"R. Kruse, L. A. Gage, K. Washington, D. Oliver","doi":"10.4155/CLI.15.52","DOIUrl":"https://doi.org/10.4155/CLI.15.52","url":null,"abstract":"Conducting prospective studies in hospices can be difficult. We conducted a systematic review to find randomized trials that have been conducted in US hospices and to review them for quality and potential bias. Ten studies met our inclusion criteria; a wide variety of outcomes were studied. Most of the studies had at least moderate risk of bias due either to incomplete reporting of methods or the inability to blind investigators. To provide better evidence-based hospice care, more well-designed trials that are consistently reported are needed.","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"10 1","pages":"1-8"},"PeriodicalIF":0.0,"publicationDate":"2015-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84221689","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}
Background: Nearly 1/3 of the world’s population is infected with Mycobacterium tuberculosis (Mtb). Simple, effective treatment regimens could improve global tubercolosis (TB) treatment and prevention. We review the literature on the use of isoniazid and rifapentine for the treatment of TB infection. Methods: We performed a literature search with the terms ‘rifapentine’ and ‘tuberculosis’ and ‘treatment.’ Results: We identified and summarized the data for five randomized controlled trials for latent TB infection (LTBI) and seven randomized controlled trials for use in active pulmonary TB. Conclusion: Isoniazid and rifapentine given once weekly for 12 weeks is an effective, well-tolerated short course regimen for latent tuberculosis. It is also an effective combination in the continuation phase of active TB treatment in HIV-negative individuals without cavitary disease.
{"title":"A review of rifapentine for treating active and latent tuberculosis","authors":"M. Haas, R. Belknap","doi":"10.4155/CLI.15.49","DOIUrl":"https://doi.org/10.4155/CLI.15.49","url":null,"abstract":"Background: Nearly 1/3 of the world’s population is infected with Mycobacterium tuberculosis (Mtb). Simple, effective treatment regimens could improve global tubercolosis (TB) treatment and prevention. We review the literature on the use of isoniazid and rifapentine for the treatment of TB infection. Methods: We performed a literature search with the terms ‘rifapentine’ and ‘tuberculosis’ and ‘treatment.’ Results: We identified and summarized the data for five randomized controlled trials for latent TB infection (LTBI) and seven randomized controlled trials for use in active pulmonary TB. Conclusion: Isoniazid and rifapentine given once weekly for 12 weeks is an effective, well-tolerated short course regimen for latent tuberculosis. It is also an effective combination in the continuation phase of active TB treatment in HIV-negative individuals without cavitary disease.","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"1 1","pages":"829-838"},"PeriodicalIF":0.0,"publicationDate":"2015-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83505812","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}
The Institute of Medicine report in 2010 highlighted the need for changes in the framework for clinical cancer research in USA. The newly formed Big Ten Cancer Research Consortium was developed with attention to the challenges of clinical trial development, with special focus on collaborative science, the approval process and efficiencies in development and completion of clinical trials. The consortium provides for the development of team research with established leaders from academic institutions with an additional emphasis on mentoring junior investigators within and across institutions.
{"title":"The Big Ten Cancer Research Consortium: teaming up to fight cancer","authors":"S. Goodin, R. DiPaola, P. Loehrer","doi":"10.4155/CLI.15.45","DOIUrl":"https://doi.org/10.4155/CLI.15.45","url":null,"abstract":"The Institute of Medicine report in 2010 highlighted the need for changes in the framework for clinical cancer research in USA. The newly formed Big Ten Cancer Research Consortium was developed with attention to the challenges of clinical trial development, with special focus on collaborative science, the approval process and efficiencies in development and completion of clinical trials. The consortium provides for the development of team research with established leaders from academic institutions with an additional emphasis on mentoring junior investigators within and across institutions.","PeriodicalId":10369,"journal":{"name":"Clinical investigation","volume":"14 1","pages":"793-796"},"PeriodicalIF":0.0,"publicationDate":"2015-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91475830","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}
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