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Felice Francavilla - One of the best experts on this subject based on the ideXlab platform.
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ORIGINAL RESEARCH—ERECTILE DYSFUNCTION Erectile Dysfunction is the Main Determinant of Psychological Distress in Men with Spinal Cord Injury
2012Co-Authors: Arcangelo Barbonetti, Francesca Cavallo, Giorgio Felzani, Sandro Francavilla, Felice FrancavillaAbstract:Introduction. The weight of erectile dysfunction (ED) among the various Determinants of psychological distress in men with spinal cord injury (SCI) reMains to be clarified. Aim. The aim of this article was to evaluate psychological distress features in SCI men with or without ED. Methods. Forty consecutive patients with neurologically stable SCI were included in the study. Functional indepen- dence (FI) was assessed by Barthel Index (BI), which was divided into global score (questions 1-10) and bowel/bladder subscore (questions 5 and 6). Erectile function was evaluated with Sexual Health Inventory for Men (SHIM). Main Outcome Measures. Psychological distress was assessed with the Symptom Checklist-90-revised (SCL-90-R), scoringnineprimarydimensionsandtheircombinationasGlobalSeverityIndex,aglobalindexofpsychologicaldistress. Results. All SCL-90-R scores and the percentage of patients with scores >75th percentile of the entire study population were significantly higher in the group with ED (N = 21) than without ED (N = 19). Most of SCL-90-R subscales were inversely correlated with SHIM score. ED was exhibited by a high proportion (84%) of men with thoracolumbar lesions but by no patients with cervical lesions. Men with cervical lesions exhibited significantly lower SCL-90-R scores than those with thoracolumbar lesions, in spite of lower FI. However, the thoracolumbar group also reported a more severe bowel/bladder dysfunction. At multivariate logistic regression analysis, ED score significantly explained the variance of most of SCL-90-R dimension scores, whereas no association was revealed between global BI and any score of SCL-90-R dimensions. Bowel/bladder BI explained only to a very low extent the variance of depressive symptoms. Conclusions. Healthcare providers should be aware of the importance of managing ED in spinal cord-injured men, as it represents a major Determinant of their psychological distress, independently of the degree of FI impairment. Barbonetti A, Cavallo F, Felzani G, Francavilla S, and Francavilla F. Erectile dysfunction is the Main Determinant of psychological distress in men with spinal cord injury. J Sex Med 2012;9:830-836.
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Erectile dysfunction is the Main Determinant of psychological distress in men with spinal cord injury.
The journal of sexual medicine, 2011Co-Authors: Arcangelo Barbonetti, Francesca Cavallo, Giorgio Felzani, Sandro Francavilla, Felice FrancavillaAbstract:ABSTRACT Introduction The weight of erectile dysfunction (ED) among the various Determinants of psychological distress in men with spinal cord injury (SCI) reMains to be clarified. Aim The aim of this article was to evaluate psychological distress features in SCI men with or without ED. Methods Forty consecutive patients with neurologically stable SCI were included in the study. Functional independence (FI) was assessed by Barthel Index (BI), which was divided into global score (questions 1–10) and bowel/bladder subscore (questions 5 and 6). Erectile function was evaluated with Sexual Health Inventory for Men (SHIM). Main Outcome Measures Psychological distress was assessed with the Symptom Checklist‐90‐revised (SCL‐90‐R), scoring nine primary dimensions and their combination as Global Severity Index, a global index of psychological distress. Results All SCL‐90‐R scores and the percentage of patients with scores >75th percentile of the entire study population were significantly higher in the group with ED (N = 21) than without ED (N = 19). Most of SCL‐90‐R subscales were inversely correlated with SHIM score. ED was exhibited by a high proportion (84%) of men with thoracolumbar lesions but by no patients with cervical lesions. Men with cervical lesions exhibited significantly lower SCL‐90‐R scores than those with thoracolumbar lesions, in spite of lower FI. However, the thoracolumbar group also reported a more severe bowel/bladder dysfunction. At multivariate logistic regression analysis, ED score significantly explained the variance of most of SCL‐90‐R dimension scores, whereas no association was revealed between global BI and any score of SCL‐90‐R dimensions. Bowel/bladder BI explained only to a very low extent the variance of depressive symptoms. Conclusions Healthcare providers should be aware of the importance of managing ED in spinal cord‐injured men, as it represents a major Determinant of their psychological distress, independently of the degree of FI impairment. Barbonetti A, Cavallo F, Felzani G, Francavilla S, and Francavilla F. Erectile dysfunction is the Main Determinant of psychological distress in men with spinal cord injury. J Sex Med 2012;9:830–836.
Philip C Noble - One of the best experts on this subject based on the ideXlab platform.
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femoral bowing is Main Determinant of the proper alignment to restore mechanical axis in total knee arthroplasty
Orthopaedic Proceedings, 2018Co-Authors: R Megahed, O Stocks, Sabir K Ismaily, G Stocks, Philip C NobleAbstract:IntroductionThe success of knee replacement surgery depends, in part, on restoration of the correct alignment of the leg with respect to the load-bearing vector passing from the hip to the ankle (the mechanical axis). Conventional thinking is that the correct angle of resection of the distal femur (Valgus Cut Angle, VCA) depends on femoral length or femoral offset, though femoral bowing, in addition to length and medial offset, may also have a significant influence on the VCA. We hypothesized that femoral bowing has a strong effect on the VCA necessary to restore physiologic alignment after arthroplasty or osteotomy.MethodsA total of 102 long-leg radiographs were obtained from patients scheduled for primary total knee arthroplasty. The patients on average were 41% male 59% female, 67.9 ± 11.1 years, 67.0 ± 4.7 in, 192 ± 43 lbs, and had a BMI of 29.7 ± 4.8. All radiographs were prepared with the feet placed in identical rotation and the patellae pointing forward, and were excluded if there was evidence of ...
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femoral bowing is Main Determinant of the proper alignment to restore mechanical axis in total knee arthroplasty
Journal of Bone and Joint Surgery-british Volume, 2016Co-Authors: R Megahed, O Stocks, Sabir K Ismaily, G Stocks, Philip C NobleAbstract:Introduction The success of knee replacement surgery depends, in part, on restoration of the correct alignment of the leg with respect to the load-bearing vector passing from the hip to the ankle (the mechanical axis). Conventional thinking is that the correct angle of resection of the distal femur (Valgus Cut Angle, VCA) depends on femoral length or femoral offset, though femoral bowing, in addition to length and medial offset, may also have a significant influence on the VCA. We hypothesized that femoral bowing has a strong effect on the VCA necessary to restore physiologic alignment after arthroplasty or osteotomy. Methods A total of 102 long-leg radiographs were obtained from patients scheduled for primary total knee arthroplasty. The patients on average were 41% male 59% female, 67.9 ± 11.1 years, 67.0 ± 4.7 in, 192 ± 43 lbs, and had a BMI of 29.7 ± 4.8. All radiographs were prepared with the feet placed in identical rotation and the patellae pointing forward, and were excluded if there was evidence of malrotation, as defined by (i) a difference in the medial head offsets of the right and left femur of >3mm, (ii) a difference in the width of the tibiofibular syndesmoses, or (iii) a difference in the rotation of one foot compared to the other. The following anatomic variables were measured on each radiograph: (i) the neck shaft angle (NSA) of the femur, (ii) the length of the femur, (iii) the length of the femoral shaft, (iv) the medial head offset, (v) the medial-lateral bow of the distal femur, (vi) the hip- knee axis angle, (vii) the mechanical axis deviation of the extremity at the knee, (viii) the medio-lateral bow of the tibia, and (ix) the valgus cut angle required to restore the mechanical axis to the center of the knee during surgery (VCA). Bivariate plots were constructed using the measurements thought to influence the VCA: femoral bowing, femoral offset, and length of femur. Multivariate regression was then used to find the variable that had the strongest effect on the VCA. Results The bivariate plot of offset and VCA yielded an R2 of 0.02544 (p = 0.11) was not statistically significant. However, the bivariate plot of femoral length and VCA yielded an R2 of 0.1294 (p = 0.0002) showing significant correlation. Lastly, the bivariate plot of femoral bowing and VCA yielded an R2 of 0.59136 (p Discussion While clinicians performing knee replacements typically do not consider femoral bowing when selecting the valgus angle appropriate for each patient, our findings demonstrate that femoral bowing has a potent effect on VCA. The multivariate regression indicated that femoral bowing had the highest effect on VCA followed by offset and femoral length. These findings suggest that surgeons should consider measuring long alignment radiographs before performing a total knee arthroplasty.
Shoshana Yakar - One of the best experts on this subject based on the ideXlab platform.
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reduced serum igf 1 associated with hepatic osteodystrophy is a Main Determinant of low cortical but not trabecular bone mass
Journal of Bone and Mineral Research, 2018Co-Authors: Zhongbo Liu, Tianzhen Han, Haim Werner, Clifford J. Rosen, Mitchell B. Schaffler, Shoshana YakarAbstract:Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was Maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a Main Determinant of low cortical but not trabecular bone mass. © 2017 American Society for Bone and Mineral Research.
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Reduced Serum IGF‐1 Associated With Hepatic Osteodystrophy Is a Main Determinant of Low Cortical but Not Trabecular Bone Mass
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2017Co-Authors: Zhongbo Liu, Tianzhen Han, Haim Werner, Clifford J. Rosen, Mitchell B. Schaffler, Shoshana YakarAbstract:Hepatic osteodystrophy is multifactorial in its pathogenesis. Numerous studies have shown that impairments of the hepatic growth hormone/insulin-like growth factor-1 axis (GH/IGF-1) are common in patients with non-alcoholic fatty liver disease, chronic viral hepatitis, liver cirrhosis, and chronic cholestatic liver disease. Moreover, these conditions are also associated with low bone mineral density (BMD) and greater fracture risk, particularly in cortical bone sites. Hence, we addressed whether disruptions in the GH/IGF-1 axis were causally related to the low bone mass in states of chronic liver disease using a mouse model of liver-specific GH-receptor (GHR) gene deletion (Li-GHRKO). These mice exhibit chronic hepatic steatosis, local inflammation, and reduced BMD. We then employed a crossing strategy to restore liver production of IGF-1 via hepatic IGF-1 transgene (HIT). The resultant Li-GHRKO-HIT mouse model allowed us to dissect the roles of liver-derived IGF-1 in the pathogenesis of osteodystrophy during liver disease. We found that hepatic IGF-1 restored cortical bone acquisition, microarchitecture, and mechanical properties during growth in Li-GHRKO-HIT mice, which was Maintained during aging. However, trabecular bone volume was not restored in the Li-GHRKO-HIT mice. We found increased bone resorption indices in vivo as well as increased basal reactive oxygen species and increased mitochondrial stress in osteoblast cultures from Li-GHRKO and the Li-GHRKO-HIT compared with control mice. Changes in systemic markers such as inflammatory cytokines, osteoprotegerin, osteopontin, parathyroid hormone, osteocalcin, or carboxy-terminal collagen cross-links could not fully account for the diminished trabecular bone in the Li-GHRKO-HIT mice. Thus, the reduced serum IGF-1 associated with hepatic osteodystrophy is a Main Determinant of low cortical but not trabecular bone mass. © 2017 American Society for Bone and Mineral Research.
Baptiste Saudemont - One of the best experts on this subject based on the ideXlab platform.
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the fitness cost of mis splicing is the Main Determinant of alternative splicing patterns
Genome Biology, 2017Co-Authors: Baptiste Saudemont, Alexandra Popa, Joanna L Parmley, Vincent Rocher, Corinne Blugeon, Anamaria Necsulea, Eric MeyerAbstract:Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of protein variants or to the regulation of gene expression via nonsense-mediated messenger RNA (mRNA) decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts and the question of the relative proportion of splicing errors to functional splice variants reMains highly debated. We propose a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We analyzed the transcriptome of the intron-rich eukaryote Paramecium tetraurelia. We show that in both normal and in NMD-deficient cells, AS rates strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed for AS events that are detectable by NMD as well as for those that are not, which invalidates the hypothesis of a link with the regulation of gene expression. Our results show that in genes with a median expression level, 92–98% of observed splice variants correspond to errors. We observed the same patterns in human transcriptomes and we further show that AS rates correlate with the fitness cost of splicing errors. These observations indicate that genes under weaker selective pressure accumulate more maladaptive substitutions and are more prone to splicing errors. Thus, to a large extent, patterns of gene expression variants simply reflect the balance between selection, mutation, and drift.
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the fitness cost of mis splicing is the Main Determinant of alternative splicing patterns
bioRxiv, 2017Co-Authors: Baptiste Saudemont, Alexandra Popa, Joanna L Parmley, Vincent Rocher, Corinne Blugeon, Anamaria Necsulea, Eric Meyer, Laurent DuretAbstract:Most eukaryotic genes are subject to alternative splicing (AS), which may contribute to the production of functional protein variants or to the regulation of gene expression, notably via nonsense-mediated mRNA decay (NMD). However, a fraction of splice variants might correspond to spurious transcripts, and the question of the relative proportion of splicing errors vs. functional splice variants reMains highly debated. We propose here a test to quantify the fraction of AS events corresponding to errors. This test is based on the fact that the fitness cost of splicing errors increases with the number of introns in a gene and with expression level. We first analyzed the transcriptome of the intron-rich unicellular eukaryote Paramecium tetraurelia. We show that both in normal and in NMD-deficient cells, AS rates (intron retention, alternative splice site usage or cryptic intron splicing) strongly decrease with increasing expression level and with increasing number of introns. This relationship is observed both for AS events that are detectable by NMD or not, which invalidates the hypothesis of a possible link with the regulation of gene expression. Our results indicate that in genes with a median expression level, 92%-98% of observed splice variants correspond to errors. Interestingly, we observed the same patterns in human transcriptomes. These results are consistent with the mutation-selection-drift theory, which predicts that genes under weaker selective pressure should accumulate more maladaptive substitutions, and therefore should be more prone to errors of gene expression.
Phillipa M Kyle - One of the best experts on this subject based on the ideXlab platform.
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is zygosity or chorionicity the Main Determinant of fetal outcome in twin pregnancies
Obstetrical & Gynecological Survey, 2006Co-Authors: Stephen G M Carroll, Linda Tyfield, Louise Reeve, Helen Porter, Peter Soothill, Phillipa M KyleAbstract:Two thirds of twin pregnancies are dizygotic, and all these twin pairs are dichorionic. Among monozygotic twins, 70% have monochorionic and 30% have dichorionic placentation. All monochorionic twins and 10% of dichorionic twins are monozygotic. Observations that fetal outcomes are worse for monochorionic than for dichorionic twins have been ascribed to complications caused by placental vascular anastomoses, but whether absolute outcomes are related to monozygosity or monochorionicity reMains uncertain. This prospective study of women having twin pregnancies in the years 1998-2000 was intended to relate fetal outcomes to zygosity and chorionicity. The study compared two kinds of dichorionic twin pregnancies resulting in live births: 92 dizygotic and thus dichorionic pregnancies and 15 monozygotic, dichorionic pregnancies. Zygosity was determined using microsatellite markers amplified by the polymerase chain reaction technique, and the placentas were examined microscopically to determine chorionic type. In all 51 dizygotic twin pregnancies, in which the infants were of the same sex, the placenta was classified as dichorionic. All 41 pairs of different-sex twins were dizygotic. In seven of 39 pairs of monozygotic monochorionic twins, either both twins were not born alive or they were delivered before 24 weeks gestation. Monochorionic pregnancies had significantly lower gestational ages at delivery as well as significantly lower birth weights. Cases with birth weight discordance of more than 25% were more numerous in monochorionic pregnancies than in the other groups. All 10 fetal losses were in the monochorionic group; six of them were related to twin-twin transfusion. No significant differences in any parameters were found between the monozygotic dichorionic and dizygotic groups. These findings demonstrate that, in twin pregnancies, fetal outcomes are related to chorionicity, not zygosity.
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is zygosity or chorionicity the Main Determinant of fetal outcome in twin pregnancies
American Journal of Obstetrics and Gynecology, 2005Co-Authors: Stephen G M Carroll, Linda Tyfield, Louise Reeve, Helen Porter, Peter Soothill, Phillipa M KyleAbstract:Objective The purpose of this study was to examine whether fetal outcome in twin pregnancies is dependent on zygosity or chorionicity. Study design This was a prospective observational study comprised of women with twin pregnancies who attended the fetal medicine unit at St Michael's Hospital, Bristol, Ireland, during the years 1998 to 2000 and who were delivered in hospitals in south west England. After delivery, zygosity was determined with umbilical cord blood with the use of microsatellite markers that were amplified by polymerase chain reaction. Placentae were examined histologically for chorionic type. The perinatal outcomes of 3 groups of monozygotic monochorionic, monozygotic dichorionic, and dizygotic pregnancies were compared with the use of the Mann-Whitney U test and the Fisher's exact test. Results All 92 dizygotic and 15 monozygotic dichorionic pregnancies resulted in live births. In 7 of the 39 cases in the monozygotic monochorionic group, either both twins were not live born or delivery occurred 25% in the monochorionic pregnancies compared with the other 2 groups (P Conclusion Fetal outcome in twin pregnancies is related to chorionicity rather than zygosity.
