Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graf...Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B m RNAs, FOXP3 m RNA, CXCL9/CXCL10 and mi RNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival.展开更多
AIM：To provide a side-by-side analysis of the summary of safety and effectiveness data（SSED）submitted to the FDA for the KAMRA and Raindrop corneal inlays for the correction of presbyopia.METHODS：SSED reports subm...AIM：To provide a side-by-side analysis of the summary of safety and effectiveness data（SSED）submitted to the FDA for the KAMRA and Raindrop corneal inlays for the correction of presbyopia.METHODS：SSED reports submitted to the FDA for KAMRA and Raindrop were compared with respect to loss of corrected distance visual acuity（CDVA）,adverse event rates,induction of astigmatism,retention of contrast sensitivity,stability of manifest refractive spherical equivalent（MRSE）,and achieved monocular uncorrected near visual acuity（UNVA）at 24mo.RESULTS：Totally 442/508 of KAMRA patients and344/373 Raindrop patients remained enrolled in the clinical trials at 24mo.The proportion of KAMRA and Raindrop patients who lost≥2 lines of CDVA at 24mo was 3.4%and1%,respectively.The adverse event rate was comparable between the devices.No significant inductions of astigmatism were noted.Both technologies induced a transient myopic shift in MRSE followed by a hyperopic shift and subsequent stabilization.Totally 87%of KAMRA and 98%of Raindrop patients attained a monocular UNVA of J5（20/40）or better at 24mo,28%of KAMRA and 67%of Raindrop patients attained a monocular UNVA of J1（20/20）or better at 24mo.CONCLUSION：Both devices can be considered safe and effective,however,the results of corneal inlay implantation are mixed,and long-term patient satisfaction will likely depend on subjective expectations about the capabilities of the inlays.Variability in surgical technique and postoperative care within and between the two clinical trials diminishes the comparative power of this article.展开更多
We report a bioinformatic analysis of the datasets of sequences of all ten genes from the 2009 H1N1 influenza A pandemic in the state of Wisconsin. The gene with the greatest summed information entropy was found to be...We report a bioinformatic analysis of the datasets of sequences of all ten genes from the 2009 H1N1 influenza A pandemic in the state of Wisconsin. The gene with the greatest summed information entropy was found to be the hemagglutinin (HA) gene. Based upon the viral ID identifier of the HA gene sequence, the sequences of all of the genes were sorted into two subsets, depending upon whether the nucleotide occupying the position of maximum entropy, position 658 of the HA sequence, was either A or U. It was found that the information entropy (H) distributions of subsets differed significantly from each other, from H distributions of randomly generated subsets and from the H distributions of the complete datasets of each gene. Mutual information (MI) values facilitated identification of nine nucleotide positions, distributed over seven of the influenza genes, at which the nucleotide subsets were disjoint, or almost disjoint. Nucleotide frequencies at these nine positions were used to compute mutual information values that subsequently served as weighting factors for edges in a graph net-work. Seven of the nucleotide positions in the graph network are sites of synonymous mutations. Three of these sites of synonymous mutation are within a single gene, the M1 gene, which occupied the position of greatest graph centrality. It is proposed that these bioinformatic and network graph results may reflect alterations in M1-mediated viral packaging and exteriorization, known to be susceptible to synonymous mutations.展开更多
AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic...AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.展开更多
Migrant workers, particularly gold mining workers, have been identified as a group at risk for HIV and sexually transmitted infections (STI). A cross-sectional study was undertaken on the correlates of human immunodef...Migrant workers, particularly gold mining workers, have been identified as a group at risk for HIV and sexually transmitted infections (STI). A cross-sectional study was undertaken on the correlates of human immunodeficiency virus (HIV) and syphilis infections in a sample of migrants (Ghanaian citizens [156] and non-Ghanaian citizens [8]) working in a gold mining centres in Konongo, Ghana. The study was conducted between the months of January 2013 to December 2013. Of a total of 600 eligible migrant workers, only 164 (27.33%;males 114, females 50) of the eligible migrants took part in the study. Subjects voluntarily completed a risk-factor questionnaire and provided blood specimen for testing for the presence of antibodies to HIV and Treponema pallidum, the causative agent of syphilis. These data were analyzed using both univariate and multivariate techniques. The median age of the participants was 29.0 years (range 18 - 62 years). Of the 164 migrant workers tested, HIV and syphilis seroprevalence were 6.7% and 3.7% respectively. On multivariate analysis, the independent determinants for HIV infection were being female [odds ratio (OR) 2.94;95% confidence interval (95% CI 0.86 - 10.0);unmarried (OR 10.13;95% CI 1.2 - 81.09);drug use (OR 3.76;95% CI 0.38 - 36.3);and blood transfusion (OR 2.45;95% CI 0.27 - 22.37). Similarly, on multivariate analysis, the independent determinants for syphilis infection were having concurrent sexual partners (OR 2.16;95% CI 0.38 - 12.12);and blood transfusion (OR 5.07;95% CI 0.51 - 50.37). Consistent with similar studies worldwide, our results suggest high prevalence of HIV and syphilis infections among migrant workers who work in gold mining centres in Ghana.展开更多
文摘Despite the introduction of potent immunosuppressive medications within recent decades, acute rejection still accounts for up to 12% of all graft losses, and is generally associated with an increased risk of late graft failure. Current detection of acute rejection relies on frequent monitoring of the serum creatinine followed by a diagnostic renal biopsy. This strategy is flawed since an alteration in the serum creatinine is a late clinical event and significant irreversible histologic damage has often already occurred. Furthermore, biopsies are invasive procedures that carry their own inherent risk. The discovery of non-invasive urinary biomarkers to help diagnose acute rejection has been the subject of a significant amount of investigation. We review the literature on urinary biomarkers here, focusing on specific markers perforin and granzyme B m RNAs, FOXP3 m RNA, CXCL9/CXCL10 and mi RNAs. These and other biomarkers are not yet widely used in clinical settings, but our review of the literature suggests that biomarkers may correlate with biopsy findings and provide an important early indicator of rejection, allowing more rapid treatment and better graft survival.
文摘AIM：To provide a side-by-side analysis of the summary of safety and effectiveness data（SSED）submitted to the FDA for the KAMRA and Raindrop corneal inlays for the correction of presbyopia.METHODS：SSED reports submitted to the FDA for KAMRA and Raindrop were compared with respect to loss of corrected distance visual acuity（CDVA）,adverse event rates,induction of astigmatism,retention of contrast sensitivity,stability of manifest refractive spherical equivalent（MRSE）,and achieved monocular uncorrected near visual acuity（UNVA）at 24mo.RESULTS：Totally 442/508 of KAMRA patients and344/373 Raindrop patients remained enrolled in the clinical trials at 24mo.The proportion of KAMRA and Raindrop patients who lost≥2 lines of CDVA at 24mo was 3.4%and1%,respectively.The adverse event rate was comparable between the devices.No significant inductions of astigmatism were noted.Both technologies induced a transient myopic shift in MRSE followed by a hyperopic shift and subsequent stabilization.Totally 87%of KAMRA and 98%of Raindrop patients attained a monocular UNVA of J5（20/40）or better at 24mo,28%of KAMRA and 67%of Raindrop patients attained a monocular UNVA of J1（20/20）or better at 24mo.CONCLUSION：Both devices can be considered safe and effective,however,the results of corneal inlay implantation are mixed,and long-term patient satisfaction will likely depend on subjective expectations about the capabilities of the inlays.Variability in surgical technique and postoperative care within and between the two clinical trials diminishes the comparative power of this article.
文摘We report a bioinformatic analysis of the datasets of sequences of all ten genes from the 2009 H1N1 influenza A pandemic in the state of Wisconsin. The gene with the greatest summed information entropy was found to be the hemagglutinin (HA) gene. Based upon the viral ID identifier of the HA gene sequence, the sequences of all of the genes were sorted into two subsets, depending upon whether the nucleotide occupying the position of maximum entropy, position 658 of the HA sequence, was either A or U. It was found that the information entropy (H) distributions of subsets differed significantly from each other, from H distributions of randomly generated subsets and from the H distributions of the complete datasets of each gene. Mutual information (MI) values facilitated identification of nine nucleotide positions, distributed over seven of the influenza genes, at which the nucleotide subsets were disjoint, or almost disjoint. Nucleotide frequencies at these nine positions were used to compute mutual information values that subsequently served as weighting factors for edges in a graph net-work. Seven of the nucleotide positions in the graph network are sites of synonymous mutations. Three of these sites of synonymous mutation are within a single gene, the M1 gene, which occupied the position of greatest graph centrality. It is proposed that these bioinformatic and network graph results may reflect alterations in M1-mediated viral packaging and exteriorization, known to be susceptible to synonymous mutations.
基金Supported by Translation Medicine Research Compassionate Use Program of MMI,No.2006-001Data collection was funded as part of Mueller Medical International LLC research on polyanionic saccharides as in-vivo surface active immuno-modulating agents for epithelial mediated processes at its Center for Translational Medicine Research in Foster Rhode Island
文摘AIM:To study usefulness of high-potency sucralfate(HPS)in a patient with chemoradiation mucositis and discuss its mechanism of action.METHODS:HPS,a non-covalently cross-link of sucralfate,cations and bidentate anionic chelators,has a maintains a surface concentration of sucralfate 3 h following administration that is 7-23 fold that possible with standard-potency sucralfate.The accelerated mucosal healing and pain alleviation of HPS in patients with erosive esophageal reflux,prompted its use in this patient with chemoradiation mucositis of the oropharynx and alimentary tract.A literature-based review of the immuno-modulatory effects of sucralfate is discussed.RESULTS:Within 48 h of intervention:(1)there was complete disappearance of oral mucositis lesions;tenderness with(2)patient-reported disappearance of pain,nausea and diarrhea;patient required(3)no opiate analgesia and(4)no tube-feeding supplements to regular diet.Dysgeusia and xerostomia persisted.A modified Naranjo Questionnaire score of 10 supported the likelihood that HPS intervention caused the observed clinical effects.No adverse reactions noted.CONCLUSION:In this patient HPS was useful to treat chemo-radiation mucositis of the oropharynx and alimentary tract.HPS may directly or indirectly facilitate an immunomodulatory mechanism involving accelerated growth factor activation,which may be a new target for therapeutic intervention in such patients.
文摘Migrant workers, particularly gold mining workers, have been identified as a group at risk for HIV and sexually transmitted infections (STI). A cross-sectional study was undertaken on the correlates of human immunodeficiency virus (HIV) and syphilis infections in a sample of migrants (Ghanaian citizens [156] and non-Ghanaian citizens [8]) working in a gold mining centres in Konongo, Ghana. The study was conducted between the months of January 2013 to December 2013. Of a total of 600 eligible migrant workers, only 164 (27.33%;males 114, females 50) of the eligible migrants took part in the study. Subjects voluntarily completed a risk-factor questionnaire and provided blood specimen for testing for the presence of antibodies to HIV and Treponema pallidum, the causative agent of syphilis. These data were analyzed using both univariate and multivariate techniques. The median age of the participants was 29.0 years (range 18 - 62 years). Of the 164 migrant workers tested, HIV and syphilis seroprevalence were 6.7% and 3.7% respectively. On multivariate analysis, the independent determinants for HIV infection were being female [odds ratio (OR) 2.94;95% confidence interval (95% CI 0.86 - 10.0);unmarried (OR 10.13;95% CI 1.2 - 81.09);drug use (OR 3.76;95% CI 0.38 - 36.3);and blood transfusion (OR 2.45;95% CI 0.27 - 22.37). Similarly, on multivariate analysis, the independent determinants for syphilis infection were having concurrent sexual partners (OR 2.16;95% CI 0.38 - 12.12);and blood transfusion (OR 5.07;95% CI 0.51 - 50.37). Consistent with similar studies worldwide, our results suggest high prevalence of HIV and syphilis infections among migrant workers who work in gold mining centres in Ghana.
