For a direct-sequence code division multiple access system with hard decision parallel interferen... more For a direct-sequence code division multiple access system with hard decision parallel interference cancellation (DS-CDMA with HD-PIC), we derive analytical results concerning the probability of a bit error. More precisely, we investigate the exponential rate Hk(s) of a CDMA system with s stages of HD-PIC, with k users and processing gain equal to n, as n→∞. The rate is a good measure of performance and allows us to compare the performance after applying several stages of HD-PIC. Furthermore, we derive results for the asymptotic behaviour of the exponential rates H k(s) as k→∞. Finally, we investigate what happens when, for k fixed, we perform many stages of HD-PIC. These results can be used to guarantee a small BEP by applying a number of HD-PIC stages that depends on the number of users. The results show analytically that HD-PIC significantly improves performance. This conference paper is based upon and extends results and techniques of Van der Hofstad et al. (2000), that we briefly discuss
Complexin II is reduced in Huntington's disease (HD) patients and in the R6 ⁄ 2 mouse model of HD... more Complexin II is reduced in Huntington's disease (HD) patients and in the R6 ⁄ 2 mouse model of HD. Mice lacking complexin II (Cplx2 -⁄mice) show selective cognitive deficits that reflect those seen in R6 ⁄ 2 mice. To determine whether or not there is a common mechanism that might underlie the cognitive deficits, long-term potentiation (LTP) was examined in the CA3 region of hippocampal slices from R6 ⁄ 2 mice and Cplx2 -⁄mice. While associational ⁄ commissural (A ⁄ C) LTP was not significantly different, mossy fibre (MF) LTP was significantly reduced in slices from R6 ⁄ 2 mice and Cplx2 -⁄mice compared with wild-type (WT) and Cplx2 + ⁄ + control mice. MF field excitatory postsynaptic potentials (fEPSPs) in response to paired stimuli were not significantly different between control mice and R6 ⁄ 2 or Cplx2 -⁄mice, suggesting that MF basal glutamate release is unaffected. Forskolin (30 lm) caused an increase in glutamate release at MF synapses in slices from R6 ⁄ 2 mice and from Cplx2 -⁄mice that was not significantly different from that seen in control mice, indicating that the capacity for increased glutamate release is not diminished. Thus, R6 ⁄ 2 mice and Cplx2 -⁄mice have a common selective impairment of MF LTP in the CA3 region. Together, these data suggest that complexin II is required for MF LTP, and that depletion of complexin II causes a selective impairment in MF LTP in the CA3 region. This impairment in MF LTP could contribute to spatial learning deficits observed in R6 ⁄ 2 and Cplx2 -⁄mice.
Snower KN, Lynn JB CVS Caremark, Northbrook, IL, USA OBJECTIVES: Adherence to medications is an i... more Snower KN, Lynn JB CVS Caremark, Northbrook, IL, USA OBJECTIVES: Adherence to medications is an integral component of treating human immunodeficiency virus (HIV). The objective of this study was to identify factors associated with suboptimal adherence to HIV therapy (MPR < 95%). METHODS: HIV patients were identified by a pharmacy claim between January 1, 2008 and November 30, 2008, for a non-nucleoside reverse transcriptase inhibitor, protease inhibitor, nucleoside reverse transcriptase inhibitor, entry inhibitor, integrase inhibitor or combination medication, using a large de-identified administrative claims database. Medication possession ratio (MPR) was calculated during the 12 months following their index prescription for those patients continuously enrolled and with at least two fills per medication. For patients utilizing more than one HIV medication, a mean MPR was calculated, weighted by length of time on each medication. Logistic regression was used to identify factors associated with suboptimal adherence. RESULTS: The analysis included 18,497 patients (20.0% female, mean age 46.7 years). Mean MPR was 87.2% (95% CI: 86.9-87.4), with 48.6% of patients having suboptimal adherence. Suboptimal adherence was associated with female gender (OR = 1.55, 95% CI: 1.44-1.68), dispenses from retail pharmacies (OR = 1.54, 95% CI: 1.43-1.67), less than three-months supply per dispense (OR = 1.38, 95% CI: 1.26-1.52), patient age less than 45 years (OR = 1.26, 95% CI: 1.18-1.34), using more than one pharmacy for HIV medications (OR = 1.20, 95% CI: 1.11-1.29), being new to therapy (OR = 1.12, 95% CI: 1.04-1.19), taking more pills per day (OR = 1.09 for each additional pill per day, 95% CI: 1.06-1.12) and using more HIV medications (OR = 1.08 for each additional medication, 95% CI: 1.06-1.11). Type of insurance coverage and amount of copay were not significantly associated with suboptimal adherence. CON-CLUSIONS: Knowledge of factors related to suboptimal adherence can help identify HIV patients who may require additional attention during their course of care.
To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), ma... more To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), male Wistar rats were administrated HD at dosage of 200 or 400 mg/kg for 8 weeks (five-times per week). All rats were sacrificed after 8 weeks of treatment and the cerebrum cortex (CC), spinal cord (SC) and sciatic nerves (SN) were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilaments (NFs) subunits (NF-L, NF-M and NF-H) in nerve tissues of 200 and 400 mg/kg HD rats significantly decreased in both the supernatant and pellet fractions. Furthermore, significant negative correlations between NFs levels and gait abnormality were observed. As for microtubule (MT) and microfilament (MF) proteins, the levels of ␣-tubulin, -tubulin and -actin in the supernatant and pellet fraction of SN significantly decreased in 200 and 400 mg/kg HD rats and correlated negatively with gait abnormality. However, the contents of MT and MF proteins in CC and SC were inconsistently affected and had no significant correlation with gait abnormality. The levels of NF-L and NF-H in serum significantly increased, while NF-M, ␣-tubulin, -tubulin and -actin contents remain unchanged. A significant positive correlation (R = 0.9427, P < 0.01) was observed between gait abnormality and NF-H level in serum as the intoxication went on. These findings suggested that HD intoxication resulted in a progressive decline of cytoskeletal protein contents, which might be relevant to the mechanisms of HD-induced neuropathy. NF-H was the most sensitive index, which may serve as a good indicator for neurotoxicity of n-hexane or HD.
Knowledge about the molecular mechanisms involved in the pathogenesis of tumoral progression in m... more Knowledge about the molecular mechanisms involved in the pathogenesis of tumoral progression in mycosis fungoides (MF) is still scarce. Because the 9p21 locus seems to be a good target for a detailed study in MF, this prompted us to compare the mechanisms of inactivation of the p16 INK4a , p15 INK4b , and p14 ARF genes in aggressive and stable forms of MF, performing microsatellite analysis, methylation-specific polymerase chain reaction, direct sequencing, and p16 INK4a protein expression by immunohistochemistry. Additionally, the p53 gene was also sequenced in tumoral lesions. Thirty-nine patients with stable MF were studied. Alterations in p16 INK4a and p15 INK4b genes were detected in 18% and 5% of the cases, respectively. None of the cases analyzed showed alterations of the p14 ARF gene. In contrast with these findings, in the 11 patients with aggressive MF, alterations of the p16 INK4a , p15 INK4b , or p14 ARF genes were found in 8 (73%), 3 (27%), and 2 (18%) cases, respectively. A significant proportion (4/11) of these alterations were already present in the p16 INK4a gene in the initial plaque lesions in these aggressive forms of MF. Alterations in the p16 INK4a gene, either methylation or loss of heterozygosity, were clearly more frequent than those in the p15 INK4b and p14 ARF genes. These p16 INK4A alterations were confirmed using immunohistochemistry. None of the nine tumoral lesions analyzed showed mutations in exons 1-2 of the p16 INK4a gene or in exons 5-8 of the p53 gene. These results seem to suggest that 9p21 alterations, and selectively p16 INK4a silencing, could be a characteristic phenomenon in MF progression. (Lab Invest 2002, 82:123-132).
Exposure chronically to n-hexane produces peripheral–central axonopathy mediated by 2,5-hexanedio... more Exposure chronically to n-hexane produces peripheral–central axonopathy mediated by 2,5-hexanedione (HD). Previous studies have demonstrated decreases in neurofilament (NF) contents of peripheral and central nervous regions from rats intoxicated with HD, and recent analysis has demonstrated that axonal atrophy, instead of NF-filled swellings, is a specific component of morphologic alterations. To deeply investigate the alterations of cytoskeletal proteins in HD peripheral neuropathy, the relative levels of NF-L, NF-M, NF-H, α-tubulin, β-tubulin and β-actin of rat sciatic–tibial nerves were determined by SDS-PAGE and immunoblotting. HD was administrated to Wistar rats by intraperitoneal injection at dosage of 200 or 400 mg/kg/day (five-times per week). Rats were sacrificed after 6 weeks of treatment, and sciatic–tibial nerves were dissected, homogenized, and used for the determination of cytoskeletal proteins. Except for supernatant NF-L that could not be assayed, the results showed HD intoxication was associated with significant decreases in NF subunits in both of the supernatant and the pellet fractions of sciatic–tibial nerve homogenates (P<0.01), and obvious reductions in α-tubulin, β-tubulin and β-actin only in the supernatant (P<0.05 or P<0.01). Among these alterations, the falls in the levels of NF subunits tended to be greater compared to those of the other cytoskeletal proteins in all HD-exposed groups, and the trend for decrements in NF-M was greater than those in the other NF subunits. Thus, HD intoxication was associated with significant declines in cytoskeletal protein contents in rat sciatic–tibial nerves, and the decreases might be related to the involvement of the peripheral axonopathy induced by HD.
Objective: To evaluate muscle function (MF) of patients on hemodialysis (HD) and to investigate t... more Objective: To evaluate muscle function (MF) of patients on hemodialysis (HD) and to investigate the dialysis determinants of maximal voluntary handgrip strength (HGS). Methods: Forty-three patients on HD (25 men, six diabetics, 54.5 AE 12.2 y of age, 62.2 AE 51.4 mo on dialysis) were studied. HGS was measured three times with a mechanical dynamometer (Jamar) before and after HD sessions on the non-fistula side and the highest value was used for analysis. HGS values lower than the 10th percentile of an age-, gender-, and region-specific reference were considered MF loss. Biochemical and dialysis variables (ultrafiltration, interdialytic body weight gain, urea clearance, urea before and after HD, systolic and diastolic blood pressures before and after HD, and difference in systolic and diastolic blood pressures) were also examined. Results: The HGS values before and after HD values were significantly higher in men but were not statistically different before and after the HD sessions (29.8 AE 10.3 and 30.2 AE 9.9 kg for men, 14.1 AE 7.0 and 14.5 AE 6.3 kg for women). MF loss was observed in 24 patients (55.8%), 12 women and 12 men. Dialysis variables were not different between patients with and without MF loss and did not correlate with HGS measured before or after an HD session.
For a direct-sequence code division multiple access system with hard decision parallel interferen... more For a direct-sequence code division multiple access system with hard decision parallel interference cancellation (DS-CDMA with HD-PIC), we derive analytical results concerning the probability of a bit error. More precisely, we investigate the exponential rate Hk(s) of a CDMA system with s stages of HD-PIC, with k users and processing gain equal to n, as n→∞. The rate is a good measure of performance and allows us to compare the performance after applying several stages of HD-PIC. Furthermore, we derive results for the asymptotic behaviour of the exponential rates H k(s) as k→∞. Finally, we investigate what happens when, for k fixed, we perform many stages of HD-PIC. These results can be used to guarantee a small BEP by applying a number of HD-PIC stages that depends on the number of users. The results show analytically that HD-PIC significantly improves performance. This conference paper is based upon and extends results and techniques of Van der Hofstad et al. (2000), that we briefly discuss
Complexin II is reduced in Huntington's disease (HD) patients and in the R6 ⁄ 2 mouse model of HD... more Complexin II is reduced in Huntington's disease (HD) patients and in the R6 ⁄ 2 mouse model of HD. Mice lacking complexin II (Cplx2 -⁄mice) show selective cognitive deficits that reflect those seen in R6 ⁄ 2 mice. To determine whether or not there is a common mechanism that might underlie the cognitive deficits, long-term potentiation (LTP) was examined in the CA3 region of hippocampal slices from R6 ⁄ 2 mice and Cplx2 -⁄mice. While associational ⁄ commissural (A ⁄ C) LTP was not significantly different, mossy fibre (MF) LTP was significantly reduced in slices from R6 ⁄ 2 mice and Cplx2 -⁄mice compared with wild-type (WT) and Cplx2 + ⁄ + control mice. MF field excitatory postsynaptic potentials (fEPSPs) in response to paired stimuli were not significantly different between control mice and R6 ⁄ 2 or Cplx2 -⁄mice, suggesting that MF basal glutamate release is unaffected. Forskolin (30 lm) caused an increase in glutamate release at MF synapses in slices from R6 ⁄ 2 mice and from Cplx2 -⁄mice that was not significantly different from that seen in control mice, indicating that the capacity for increased glutamate release is not diminished. Thus, R6 ⁄ 2 mice and Cplx2 -⁄mice have a common selective impairment of MF LTP in the CA3 region. Together, these data suggest that complexin II is required for MF LTP, and that depletion of complexin II causes a selective impairment in MF LTP in the CA3 region. This impairment in MF LTP could contribute to spatial learning deficits observed in R6 ⁄ 2 and Cplx2 -⁄mice.
Snower KN, Lynn JB CVS Caremark, Northbrook, IL, USA OBJECTIVES: Adherence to medications is an i... more Snower KN, Lynn JB CVS Caremark, Northbrook, IL, USA OBJECTIVES: Adherence to medications is an integral component of treating human immunodeficiency virus (HIV). The objective of this study was to identify factors associated with suboptimal adherence to HIV therapy (MPR < 95%). METHODS: HIV patients were identified by a pharmacy claim between January 1, 2008 and November 30, 2008, for a non-nucleoside reverse transcriptase inhibitor, protease inhibitor, nucleoside reverse transcriptase inhibitor, entry inhibitor, integrase inhibitor or combination medication, using a large de-identified administrative claims database. Medication possession ratio (MPR) was calculated during the 12 months following their index prescription for those patients continuously enrolled and with at least two fills per medication. For patients utilizing more than one HIV medication, a mean MPR was calculated, weighted by length of time on each medication. Logistic regression was used to identify factors associated with suboptimal adherence. RESULTS: The analysis included 18,497 patients (20.0% female, mean age 46.7 years). Mean MPR was 87.2% (95% CI: 86.9-87.4), with 48.6% of patients having suboptimal adherence. Suboptimal adherence was associated with female gender (OR = 1.55, 95% CI: 1.44-1.68), dispenses from retail pharmacies (OR = 1.54, 95% CI: 1.43-1.67), less than three-months supply per dispense (OR = 1.38, 95% CI: 1.26-1.52), patient age less than 45 years (OR = 1.26, 95% CI: 1.18-1.34), using more than one pharmacy for HIV medications (OR = 1.20, 95% CI: 1.11-1.29), being new to therapy (OR = 1.12, 95% CI: 1.04-1.19), taking more pills per day (OR = 1.09 for each additional pill per day, 95% CI: 1.06-1.12) and using more HIV medications (OR = 1.08 for each additional medication, 95% CI: 1.06-1.11). Type of insurance coverage and amount of copay were not significantly associated with suboptimal adherence. CON-CLUSIONS: Knowledge of factors related to suboptimal adherence can help identify HIV patients who may require additional attention during their course of care.
To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), ma... more To investigate the mechanisms and biomarker of the neuropathy induced by 2,5-hexanedione (HD), male Wistar rats were administrated HD at dosage of 200 or 400 mg/kg for 8 weeks (five-times per week). All rats were sacrificed after 8 weeks of treatment and the cerebrum cortex (CC), spinal cord (SC) and sciatic nerves (SN) were dissected, homogenized and used for the determination of cytoskeletal proteins by western blotting. The levels of neurofilaments (NFs) subunits (NF-L, NF-M and NF-H) in nerve tissues of 200 and 400 mg/kg HD rats significantly decreased in both the supernatant and pellet fractions. Furthermore, significant negative correlations between NFs levels and gait abnormality were observed. As for microtubule (MT) and microfilament (MF) proteins, the levels of ␣-tubulin, -tubulin and -actin in the supernatant and pellet fraction of SN significantly decreased in 200 and 400 mg/kg HD rats and correlated negatively with gait abnormality. However, the contents of MT and MF proteins in CC and SC were inconsistently affected and had no significant correlation with gait abnormality. The levels of NF-L and NF-H in serum significantly increased, while NF-M, ␣-tubulin, -tubulin and -actin contents remain unchanged. A significant positive correlation (R = 0.9427, P < 0.01) was observed between gait abnormality and NF-H level in serum as the intoxication went on. These findings suggested that HD intoxication resulted in a progressive decline of cytoskeletal protein contents, which might be relevant to the mechanisms of HD-induced neuropathy. NF-H was the most sensitive index, which may serve as a good indicator for neurotoxicity of n-hexane or HD.
Knowledge about the molecular mechanisms involved in the pathogenesis of tumoral progression in m... more Knowledge about the molecular mechanisms involved in the pathogenesis of tumoral progression in mycosis fungoides (MF) is still scarce. Because the 9p21 locus seems to be a good target for a detailed study in MF, this prompted us to compare the mechanisms of inactivation of the p16 INK4a , p15 INK4b , and p14 ARF genes in aggressive and stable forms of MF, performing microsatellite analysis, methylation-specific polymerase chain reaction, direct sequencing, and p16 INK4a protein expression by immunohistochemistry. Additionally, the p53 gene was also sequenced in tumoral lesions. Thirty-nine patients with stable MF were studied. Alterations in p16 INK4a and p15 INK4b genes were detected in 18% and 5% of the cases, respectively. None of the cases analyzed showed alterations of the p14 ARF gene. In contrast with these findings, in the 11 patients with aggressive MF, alterations of the p16 INK4a , p15 INK4b , or p14 ARF genes were found in 8 (73%), 3 (27%), and 2 (18%) cases, respectively. A significant proportion (4/11) of these alterations were already present in the p16 INK4a gene in the initial plaque lesions in these aggressive forms of MF. Alterations in the p16 INK4a gene, either methylation or loss of heterozygosity, were clearly more frequent than those in the p15 INK4b and p14 ARF genes. These p16 INK4A alterations were confirmed using immunohistochemistry. None of the nine tumoral lesions analyzed showed mutations in exons 1-2 of the p16 INK4a gene or in exons 5-8 of the p53 gene. These results seem to suggest that 9p21 alterations, and selectively p16 INK4a silencing, could be a characteristic phenomenon in MF progression. (Lab Invest 2002, 82:123-132).
Exposure chronically to n-hexane produces peripheral–central axonopathy mediated by 2,5-hexanedio... more Exposure chronically to n-hexane produces peripheral–central axonopathy mediated by 2,5-hexanedione (HD). Previous studies have demonstrated decreases in neurofilament (NF) contents of peripheral and central nervous regions from rats intoxicated with HD, and recent analysis has demonstrated that axonal atrophy, instead of NF-filled swellings, is a specific component of morphologic alterations. To deeply investigate the alterations of cytoskeletal proteins in HD peripheral neuropathy, the relative levels of NF-L, NF-M, NF-H, α-tubulin, β-tubulin and β-actin of rat sciatic–tibial nerves were determined by SDS-PAGE and immunoblotting. HD was administrated to Wistar rats by intraperitoneal injection at dosage of 200 or 400 mg/kg/day (five-times per week). Rats were sacrificed after 6 weeks of treatment, and sciatic–tibial nerves were dissected, homogenized, and used for the determination of cytoskeletal proteins. Except for supernatant NF-L that could not be assayed, the results showed HD intoxication was associated with significant decreases in NF subunits in both of the supernatant and the pellet fractions of sciatic–tibial nerve homogenates (P<0.01), and obvious reductions in α-tubulin, β-tubulin and β-actin only in the supernatant (P<0.05 or P<0.01). Among these alterations, the falls in the levels of NF subunits tended to be greater compared to those of the other cytoskeletal proteins in all HD-exposed groups, and the trend for decrements in NF-M was greater than those in the other NF subunits. Thus, HD intoxication was associated with significant declines in cytoskeletal protein contents in rat sciatic–tibial nerves, and the decreases might be related to the involvement of the peripheral axonopathy induced by HD.
Objective: To evaluate muscle function (MF) of patients on hemodialysis (HD) and to investigate t... more Objective: To evaluate muscle function (MF) of patients on hemodialysis (HD) and to investigate the dialysis determinants of maximal voluntary handgrip strength (HGS). Methods: Forty-three patients on HD (25 men, six diabetics, 54.5 AE 12.2 y of age, 62.2 AE 51.4 mo on dialysis) were studied. HGS was measured three times with a mechanical dynamometer (Jamar) before and after HD sessions on the non-fistula side and the highest value was used for analysis. HGS values lower than the 10th percentile of an age-, gender-, and region-specific reference were considered MF loss. Biochemical and dialysis variables (ultrafiltration, interdialytic body weight gain, urea clearance, urea before and after HD, systolic and diastolic blood pressures before and after HD, and difference in systolic and diastolic blood pressures) were also examined. Results: The HGS values before and after HD values were significantly higher in men but were not statistically different before and after the HD sessions (29.8 AE 10.3 and 30.2 AE 9.9 kg for men, 14.1 AE 7.0 and 14.5 AE 6.3 kg for women). MF loss was observed in 24 patients (55.8%), 12 women and 12 men. Dialysis variables were not different between patients with and without MF loss and did not correlate with HGS measured before or after an HD session.
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