abstract: 30 years ago an @entity9 antibiotic was shown to have antineoplastic activity. This led to the development of well over 1000 analogues with a vast spectrum of biochemical characteristics. Many biological actions have been described. The original @entity10 are active against many types of @entity1 and are an integral part of several curative combinations. They are ineffective against other @entity1 . Although some analogues show an altered spectrum of activity or an improved therapeutic index relative to the older agents, it is not clear that @entity8 can be totally avoided with these agents. Primary and secondary resistance to @entity10 remain major clinical problems. Pharmacokinetic studies have been of limited help in explaining this. Overexpression of a surface-membrane permeability glycoprotein (Pgp) was identified in @entity2 of @entity0 who had clinical multidrug resistance in 1985. This led the way for the discovery of a number of resistance mechanisms in vitro. Some of these have been found in more than 1 type of cell line, and more than 1 mechanism may exist in a single cell. Additional resistance proteins have been identified, qualitative and quantitative alterations of topoisomerase II have been described, and some mechanisms in other systems have not yet been identified. Some of these may prove to be important in clinical drug resistance. Drugs such as @entity5 antagonists and @entity4 , studied initially for their ability to block the Pgp pump, appear to be heterogeneous in this capacity and may have additional sites of action. It will be critical for clinical studies to define the precise resistance mechanism(s) that must be reversed. To date this has been difficult, even in trials ostensibly dealing with the original Pgp. Liposomes can potentially alter @entity3 and target drug delivery to specific sites. In addition, they may permit the use of lipophilic drugs that would otherwise be difficult to administer systemically. Resistant @entity1 may be sensitive to @entity10 delivered by liposomes. To reduce @entity8 , administering @entity6 ( @entity6 ) by slow infusion through a central-venous line should be considered whenever feasible. Monitoring of cardiac ejection fraction and the use of endomyocardial biopsy will permit @entity0 to be treated safely after they reach the dose threshold at which @entity7 begins to be a potential risk. A number of structurally modified @entity10 with the potential advantages of decreased @entity8 and avoidance of multidrug resistance mechanisms are entering clinical trials. Meanwhile, the vast weight of clinical experience leaves @entity6 as a well tolerated and effective choice for most potentially @entity9 -sensitive @entity1 .

title: XXXX antibiotics in @entity1 therapy. Focus on drug resistance.

answer: @entity9


abstract: 30 years ago an @entity9 antibiotic was shown to have antineoplastic activity. This led to the development of well over 1000 analogues with a vast spectrum of biochemical characteristics. Many biological actions have been described. The original @entity10 are active against many types of @entity1 and are an integral part of several curative combinations. They are ineffective against other @entity1 . Although some analogues show an altered spectrum of activity or an improved therapeutic index relative to the older agents, it is not clear that @entity8 can be totally avoided with these agents. Primary and secondary resistance to @entity10 remain major clinical problems. Pharmacokinetic studies have been of limited help in explaining this. Overexpression of a surface-membrane permeability glycoprotein (Pgp) was identified in @entity2 of @entity0 who had clinical multidrug resistance in 1985. This led the way for the discovery of a number of resistance mechanisms in vitro. Some of these have been found in more than 1 type of cell line, and more than 1 mechanism may exist in a single cell. Additional resistance proteins have been identified, qualitative and quantitative alterations of topoisomerase II have been described, and some mechanisms in other systems have not yet been identified. Some of these may prove to be important in clinical drug resistance. Drugs such as @entity5 antagonists and @entity4 , studied initially for their ability to block the Pgp pump, appear to be heterogeneous in this capacity and may have additional sites of action. It will be critical for clinical studies to define the precise resistance mechanism(s) that must be reversed. To date this has been difficult, even in trials ostensibly dealing with the original Pgp. Liposomes can potentially alter @entity3 and target drug delivery to specific sites. In addition, they may permit the use of lipophilic drugs that would otherwise be difficult to administer systemically. Resistant @entity1 may be sensitive to @entity10 delivered by liposomes. To reduce @entity8 , administering @entity6 ( @entity6 ) by slow infusion through a central-venous line should be considered whenever feasible. Monitoring of cardiac ejection fraction and the use of endomyocardial biopsy will permit @entity0 to be treated safely after they reach the dose threshold at which @entity7 begins to be a potential risk. A number of structurally modified @entity10 with the potential advantages of decreased @entity8 and avoidance of multidrug resistance mechanisms are entering clinical trials. Meanwhile, the vast weight of clinical experience leaves @entity6 as a well tolerated and effective choice for most potentially @entity9 -sensitive @entity1 .

title: @entity9 antibiotics in XXXX therapy. Focus on drug resistance.

answer: @entity1


abstract: @entity2 is a significant problem in critically ill @entity0 . It is widespread, can colonise @entity0 quickly and causes @entity1 . However, its overall impact on morbidity and mortality in the critically ill remains unmeasured. This study was designed to investigate A. baumannii colonisation and @entity1 rates in a critically ill population over an 18-month period. Twenty-seven @entity0 from a population of 347 were identified as having A. baumannii. Sixteen were colonised, whereas 11 were infected. Eleven of the 27 @entity0 with A. baumannii died (41%). Of these, eight were colonised and three were infected. In the same period, 320 @entity0 did not have A. baumannii and their mortality rate was 20% (n = 64). The mortality rate of @entity0 with A. baumannii was significantly higher than that of @entity0 without @entity1 .

title: The impact of XXXX in the intensive care unit.

answer: @entity2


abstract: BACKGROUND: Favorable treatment outcomes with @entity1 blockade led us to explore cytokine responses in @entity3 ( @entity3 ). METHODS: Blood monocytes of 120 @entity0 and 24 healthy volunteers were subtyped by flow cytometry. Isolated blood mononuclear cells (PBMCs) were stimulated for cytokine production; this was repeated in 13 severe @entity0 during treatment with etanercept. Cytokines in pus were measured. RESULTS: CD14brightCD16dim inflammatory monocytes and patrolling monocytes were increased in @entity4 @entity0 . Cytokine production by stimulated PBMCs was low compared to controls but the cytokine gene copies did not differ, indicating post-translational inhibition. The low production of @entity5 was restored, when cells were incubated with adalimumab. In pus, high concentrations of pro-inflammatory cytokines were detected. Based on the patterns, six different cytokine profiles were discerned, which are potentially relevant for the choice of treatment. Clinical improvement with etanercept was predicted by increased production of @entity2 and @entity5 by PBMCs at week 8. CONCLUSIONS: Findings indicate compartmentalized cytokine expression in @entity3 ; high in pus but suppressed in PBMCs. This is modulated through blockade of @entity1 .

title: Compartmentalized Cytokine Responses in XXXX .

answer: @entity3


abstract: BACKGROUND: Mild @entity2 (mTBI) constitutes 75% of more than 1.5 million traumatic @entity4 annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian @entity1 is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in @entity5 . As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian @entity1 population. METHODS: From June 2013 to May 2014, @entity0 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I @entity1 center. @entity0 with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as @entity3 and/or posttraumatic @entity6 ; concussed @entity0 were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. RESULTS: There were 84 concussions and 30 nonconcussed @entity0 . Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed @entity0 . Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. CONCLUSION: The MACE showed a lower mean score for individuals with concussion, defined by @entity3 and/or posttraumatic @entity6 . However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian @entity1 population. LEVEL OF EVIDENCE: Diagnostic study, level II.

title: Utility of the Military Acute Concussion Evaluation as a screening tool for mild XXXX in a civilian @entity1 population.

answer: @entity2


abstract: BACKGROUND: Mild @entity2 (mTBI) constitutes 75% of more than 1.5 million traumatic @entity4 annually. There exists no consensus on point-of-care screening for mTBI. The Military Acute Concussion Evaluation (MACE) is a quick and easy test used by the US Army to screen for mTBI; however, its utility in civilian @entity1 is unclear. It has two parts: a history section and the Standardized Assessment of Concussion (SAC) score (0-30) previously validated in @entity5 . As a performance improvement project, our institution sought to evaluate the MACE as a concussion screening tool that could be used by housestaff in a general civilian @entity1 population. METHODS: From June 2013 to May 2014, @entity0 18 years to 65 years old with suspected concussion were given the MACE within 72 hours of admission to our urban Level I @entity1 center. @entity0 with a positive head computed tomography were excluded. Demographic data and MACE scores were recorded in prospect. Concussion was defined as @entity3 and/or posttraumatic @entity6 ; concussed @entity0 were compared with those nonconcussed. Sensitivity and specificity for each respective MACE score were used to plot a receiver operating characteristic (ROC) curve. An ROC curve area of 0.8 was set as the benchmark for a good screening test to distinguish concussion from nonconcussion. RESULTS: There were 84 concussions and 30 nonconcussed @entity0 . Both groups were similar; however, the concussion group had a lower mean MACE score than the nonconcussed @entity0 . Data analysis demonstrated the sensitivity and specificity of a range of MACE scores used to generate an ROC curve area of only 0.65. CONCLUSION: The MACE showed a lower mean score for individuals with concussion, defined by @entity3 and/or posttraumatic @entity6 . However, the ROC curve area of 0.65 highly suggests that MACE alone would be a poor screening test for mTBI in a general civilian @entity1 population. LEVEL OF EVIDENCE: Diagnostic study, level II.

title: Utility of the Military Acute Concussion Evaluation as a screening tool for mild @entity2 in a civilian XXXX population.

answer: @entity1


abstract: BACKGROUND: Lymph is pumped through the collecting lymphatic vessels by both intrinsic and extrinsic forces, propelling it downstream back into circulation. The intrinsic lymph pump relies on the spontaneous contraction of lymphatic muscles to generate the force of pumping lymph (Plp). However, the association between leg @entity1 and reduced leg Plp in the general population is unknown. Therefore, this study determined the association of leg Plp and @entity1 complaints and quality of life in healthy @entity0 . METHODS AND RESULTS: A total of 465 healthy volunteers (78 @entity0 and 387 @entity0 , age 30-85 years) filled out a questionnaire and medical history to rule out severe @entity2 . Quality of life was assessed using the Medical Outcome Study Short Form 36 (SF36). Leg Plp was measured using minimally invasive @entity3 fluorescence lymphography and an occlusion cuff technique while sitting. All @entity0 were divided into three groups according to the Plp values, as follows: @entity0 with Plp >40   mmHg in both legs, 20   mmHg-40   mmHg in either leg; and <20   mmHg in both legs were divided into the good (n=100), moderate (n=314), and poor (n=51) Plp groups, respectively. The survey revealed the poor leg Plp group was associated with more frequently complaints of leg @entity1 , as well as lower quality of life than the moderate and good Plp groups. CONCLUSION: Reduced leg Plp is significantly associated with leg @entity1 complaints and lower quality of life in the general population.

title: Low Lymphatic Pumping Pressure in the Legs Is Associated with Leg XXXX and Lower Quality of Life in Healthy Volunteers.

answer: @entity1


abstract: Increased release of @entity2 ( @entity4 ) from airway parasympathetic nerve endings is one mechanism that may contribute to increases in airway responsiveness in immunoglobulin E (IgE)-immune allergen-exposed animals. We measured @entity4 released from @entity0 @entity1 following electrical field stimulation in vitro. BALB/c @entity0 were immunized by exposure to an aerosol of 1% ovalbumin in sterile @entity3 -buffered saline for 20 min/day for 10 days. At this time, levels of ovalbumin-specific IgE were proportionately higher than ovalbumin-specific IgG. As a control, nonimmune @entity0 were similarly exposed to @entity3 -buffered saline alone. Forty-eight hours after the last aerosol, @entity1 were removed for assessment of either the contractile responses to electrical field stimulation and a cholinergic agonist ( @entity5 or @entity4 ) or release of @entity4 produced by electrical field stimulation. @entity4 in the bath was measured using high-performance liquid chromatography with electrochemical detection. The stimulation frequencies causing one-half the maximal contractile response to electrical field stimulation were 4.1 +/- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and immune @entity0 , respectively, whereas the molar concentrations of @entity5 causing one-half of the maximal contractile response did not significantly differ. In addition, the dose-response curves of immune and nonimmune @entity1 to @entity4 were superimposable. A significant increase in @entity4 release was demonstrated at both 10 and 20 Hz in @entity1 from immune @entity0 . @entity4 release (pmol.g tissue-1.min-1) from nonimmune and immune @entity0 @entity1 , respectively, were 140 +/- 8 and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at 20 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Increased XXXX release in @entity1 from allergen-exposed IgE-immune @entity0 .

answer: @entity2


abstract: Increased release of @entity2 ( @entity4 ) from airway parasympathetic nerve endings is one mechanism that may contribute to increases in airway responsiveness in immunoglobulin E (IgE)-immune allergen-exposed animals. We measured @entity4 released from @entity0 @entity1 following electrical field stimulation in vitro. BALB/c @entity0 were immunized by exposure to an aerosol of 1% ovalbumin in sterile @entity3 -buffered saline for 20 min/day for 10 days. At this time, levels of ovalbumin-specific IgE were proportionately higher than ovalbumin-specific IgG. As a control, nonimmune @entity0 were similarly exposed to @entity3 -buffered saline alone. Forty-eight hours after the last aerosol, @entity1 were removed for assessment of either the contractile responses to electrical field stimulation and a cholinergic agonist ( @entity5 or @entity4 ) or release of @entity4 produced by electrical field stimulation. @entity4 in the bath was measured using high-performance liquid chromatography with electrochemical detection. The stimulation frequencies causing one-half the maximal contractile response to electrical field stimulation were 4.1 +/- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and immune @entity0 , respectively, whereas the molar concentrations of @entity5 causing one-half of the maximal contractile response did not significantly differ. In addition, the dose-response curves of immune and nonimmune @entity1 to @entity4 were superimposable. A significant increase in @entity4 release was demonstrated at both 10 and 20 Hz in @entity1 from immune @entity0 . @entity4 release (pmol.g tissue-1.min-1) from nonimmune and immune @entity0 @entity1 , respectively, were 140 +/- 8 and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at 20 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Increased @entity2 release in XXXX from allergen-exposed IgE-immune @entity0 .

answer: @entity1


abstract: Increased release of @entity2 ( @entity4 ) from airway parasympathetic nerve endings is one mechanism that may contribute to increases in airway responsiveness in immunoglobulin E (IgE)-immune allergen-exposed animals. We measured @entity4 released from @entity0 @entity1 following electrical field stimulation in vitro. BALB/c @entity0 were immunized by exposure to an aerosol of 1% ovalbumin in sterile @entity3 -buffered saline for 20 min/day for 10 days. At this time, levels of ovalbumin-specific IgE were proportionately higher than ovalbumin-specific IgG. As a control, nonimmune @entity0 were similarly exposed to @entity3 -buffered saline alone. Forty-eight hours after the last aerosol, @entity1 were removed for assessment of either the contractile responses to electrical field stimulation and a cholinergic agonist ( @entity5 or @entity4 ) or release of @entity4 produced by electrical field stimulation. @entity4 in the bath was measured using high-performance liquid chromatography with electrochemical detection. The stimulation frequencies causing one-half the maximal contractile response to electrical field stimulation were 4.1 +/- 0.2 and 2.8 +/- 0.2 Hz (P = 0.0001) for nonimmune and immune @entity0 , respectively, whereas the molar concentrations of @entity5 causing one-half of the maximal contractile response did not significantly differ. In addition, the dose-response curves of immune and nonimmune @entity1 to @entity4 were superimposable. A significant increase in @entity4 release was demonstrated at both 10 and 20 Hz in @entity1 from immune @entity0 . @entity4 release (pmol.g tissue-1.min-1) from nonimmune and immune @entity0 @entity1 , respectively, were 140 +/- 8 and 205 +/- 22 (P = 0.013) at 10 Hz and 147 +/- 13 and 227 +/- 14 (P = 0.008) at 20 Hz.(ABSTRACT TRUNCATED AT 250 WORDS)

title: Increased @entity2 release in @entity1 from allergen-exposed IgE-immune XXXX .

answer: @entity0


abstract: The aim of this study was to investigate the prevalence of facial nerve involvement with @entity4 -enhanced magnetic resonance imaging (Gd-MRI) in @entity0 with idiopathic @entity2 (IPFP), and to discuss the localization and the pattern of enhancement. A total of 13 @entity0 (9 female, 4 male) with IFPF were included in this study. Topographic tests and electromyography (EMG) were performed, and MRI was taken. Ten subjects whose cranial MRIs were taken for nonorganic pathology served as the control group. Twelve of 13 paralytic facial nerves had enhancement on postcontrast images. Two facial nerves of the control group demonstrated enhancement. We found a correlation between the enhancement of the facial nerve and the time for recovery. The average time from the onset of @entity5 to the recovery in @entity0 with enhancement was 14 weeks, whereas it was 6 weeks in @entity0 with no enhancement. Finally, all @entity0 had complete recovery of the @entity3 . We concluded that contrast enhancement of the paralytic facial nerve can be a radiological sign of a @entity1 and may indicate a prolonged recovery.

title: Magnetic resonance imaging of the intratemporal facial nerve in idiopathic XXXX .

answer: @entity2


abstract: OBJECTIVE: To investigate serial assessments of systolic coronary flow reversal in the @entity4 related artery for predicting poor left ventricular functional recovery after reperfused acute @entity2 . SETTING: Regional hospital. @entity0 AND METHODS: 49 @entity0 with anterior acute @entity2 had transthoracic Doppler echocardiography to record coronary flow velocity in the left anterior descending coronary artery immediately after successful primary coronary angioplasty (day 0), and at 48 hours, one week, and three weeks. MAIN OUTCOME MEASURES: Coronary flow velocity at each time point; regional wall motion score index (RWMSI) at day 0 and at three weeks. Irreversible dysfunction was defined as a decrease in RWMSI to < 0.22. RESULTS: Measurements of coronary flow velocity could be made in 45 @entity0 . @entity0 were divided into three groups: no systolic flow reversal (group 1, n = 27), systolic flow reversal observed only on day 0 (group 2, n = 8), and systolic flow reversal persisting until 48 hours (group 3, n = 10). Although baseline RWMSI was similar among the three groups, the value at three weeks was significantly higher in group 3 than in the other two groups. In predicting @entity1 , the persistence of systolic flow reversal up to 48 hours had a higher positive predictive value (100%) than the presence of systolic flow reversal on day 0 (67%, p < 0.04). The negative predictive value of systolic flow reversal at 48 hours (83%) was comparable in accuracy to the presence of systolic flow reversal on day 0 (85%, NS). CONCLUSIONS: In reperfused anterior acute @entity2 , serial assessment of coronary flow velocity in the left anterior descending coronary artery is feasible using transthoracic Doppler echocardiography, and the persistence of systolic flow reversal at 48 hours is a more specific marker of @entity1 than peak @entity3 kinase or diastolic deceleration time.

title: Persistence of systolic coronary flow reversal predicts XXXX after reperfused anterior @entity2 .

answer: @entity1


abstract: OBJECTIVE: To investigate serial assessments of systolic coronary flow reversal in the @entity4 related artery for predicting poor left ventricular functional recovery after reperfused acute @entity2 . SETTING: Regional hospital. @entity0 AND METHODS: 49 @entity0 with anterior acute @entity2 had transthoracic Doppler echocardiography to record coronary flow velocity in the left anterior descending coronary artery immediately after successful primary coronary angioplasty (day 0), and at 48 hours, one week, and three weeks. MAIN OUTCOME MEASURES: Coronary flow velocity at each time point; regional wall motion score index (RWMSI) at day 0 and at three weeks. Irreversible dysfunction was defined as a decrease in RWMSI to < 0.22. RESULTS: Measurements of coronary flow velocity could be made in 45 @entity0 . @entity0 were divided into three groups: no systolic flow reversal (group 1, n = 27), systolic flow reversal observed only on day 0 (group 2, n = 8), and systolic flow reversal persisting until 48 hours (group 3, n = 10). Although baseline RWMSI was similar among the three groups, the value at three weeks was significantly higher in group 3 than in the other two groups. In predicting @entity1 , the persistence of systolic flow reversal up to 48 hours had a higher positive predictive value (100%) than the presence of systolic flow reversal on day 0 (67%, p < 0.04). The negative predictive value of systolic flow reversal at 48 hours (83%) was comparable in accuracy to the presence of systolic flow reversal on day 0 (85%, NS). CONCLUSIONS: In reperfused anterior acute @entity2 , serial assessment of coronary flow velocity in the left anterior descending coronary artery is feasible using transthoracic Doppler echocardiography, and the persistence of systolic flow reversal at 48 hours is a more specific marker of @entity1 than peak @entity3 kinase or diastolic deceleration time.

title: Persistence of systolic coronary flow reversal predicts @entity1 after reperfused anterior XXXX .

answer: @entity2


abstract: BACKGROUND: Chlamydia is the most common sexually transmitted @entity3 in Scotland, and is associated with potentially serious reproductive outcomes, including @entity4 ( @entity4 ) and @entity1 ( @entity1 ) in @entity0 . Chlamydia testing in Scotland is currently targeted towards symptomatic individuals, individuals at high risk of existing undetected infection, and young @entity0 . The cost-effectiveness of testing and treatment to prevent @entity4 and @entity1 in Scotland is uncertain. METHODS: A compartmental deterministic dynamic model of @entity2 in 15-24 year olds in Scotland was developed. The model was used to estimate the impact of a change in testing strategy from baseline (16.8% overall testing coverage; 0.4 partners notified and tested/treated per treated positive index) on @entity4 and @entity1 cases. Cost-effectiveness calculations informed by best-available estimates of the quality-adjusted life years (QALYs) lost due to @entity4 and @entity1 were also performed. RESULTS: Increasing overall testing coverage by 50% from baseline to 25.2% is estimated to result in 21% fewer cases in young @entity0 each year ( @entity4 : 703 fewer; @entity1 : 88 fewer). A 50% decrease to 8.4% would result in 20% more @entity4 (669 additional) and @entity1 (84 additional) cases occurring annually. The cost per QALY gained of current testing activities compared to no testing is   40,034, which is above the   20,000-  30,000 cost-effectiveness threshold. However, calculations are hampered by lack of reliable data. Any increase in partner notification from baseline would be cost-effective (incremental cost per QALY gained for a partner notification efficacy of 1 compared to baseline:   5,119), and would increase the cost-effectiveness of current testing strategy compared to no testing, with threshold cost-effectiveness reached at a partner notification efficacy of 1.5. However, there is uncertainty in the extent to which partner notification is currently done, and hence the amount by which it could potentially be increased. CONCLUSIONS: Current @entity2 testing strategy in Scotland is not cost-effective under the conservative model assumptions applied. However, with better data enabling some of these assumptions to be relaxed, current coverage could be cost-effective. Meanwhile, increasing partner notification efficacy on its own would be a cost-effective way of preventing @entity4 and @entity1 from current strategy.

title: Impact and cost-effectiveness of XXXX testing in Scotland: a mathematical modelling study.

answer: @entity2


abstract: UNASSIGNED: Purpose: The present work compared the behavioral outcomes of ACCS therapy delivered either intravenously (i.v.) or intracerebroventricularly (i.c.v.) after penetrating ballistic-like @entity5 (PBBI). Histological markers for neuroinflammation and neurodegeneration were employed to investigate the potential therapeutic mechanism of ACCS. Methods: Experiment-1, ACCS was administered either i.v. or i.c.v. for 1 week post-PBBI. Outcome metrics included behavioral (rotarod and Morris water maze) and gross morphological assessments. Experiment-2, @entity0 received ACCS i.c.v for either 1 or 2 weeks post-PBBI. The inflammatory response was determined by immunohistochemistry for neutrophils and microglia reactivity. @entity2 was visualized using @entity4 staining. Results: Both i.v. and i.c.v. delivery of ACCS improved motor outcome but failed to improve cognitive outcome or tissue sparing. Importantly, only i.c.v. ACCS treatment produced persistent motor improvements at a later endpoint. The i.c.v. ACCS treatment significantly reduced PBBI-induced increase in @entity6 ( @entity6 ) and ionized @entity3 binding adaptor molecule 1 ( @entity7 ) expression. Concomitant reduction of both @entity7 and @entity4 staining were detected in corpus callosum with i.c.v. ACCS treatment. Conclusions: ACCS, as a treatment for @entity1 , showed promise with regard to functional (motor) recovery and demonstrated strong capability to modulate neuroinflammatory responses that may underline functional recovery. However, the majority of beneficial effects appear restricted to the i.c.v. route of ACCS delivery, which warrants future studies examining delivery routes (e.g. intranasal delivery) which are more clinically viable for the treatment of @entity1 .

title: Treatment with amnion-derived cellular cytokine solution (ACCS) induces persistent motor improvement and ameliorates neuroinflammation in a @entity0 model of penetrating ballistic-like XXXX .

answer: @entity5


abstract: UNASSIGNED: Purpose: The present work compared the behavioral outcomes of ACCS therapy delivered either intravenously (i.v.) or intracerebroventricularly (i.c.v.) after penetrating ballistic-like @entity5 (PBBI). Histological markers for neuroinflammation and neurodegeneration were employed to investigate the potential therapeutic mechanism of ACCS. Methods: Experiment-1, ACCS was administered either i.v. or i.c.v. for 1 week post-PBBI. Outcome metrics included behavioral (rotarod and Morris water maze) and gross morphological assessments. Experiment-2, @entity0 received ACCS i.c.v for either 1 or 2 weeks post-PBBI. The inflammatory response was determined by immunohistochemistry for neutrophils and microglia reactivity. @entity2 was visualized using @entity4 staining. Results: Both i.v. and i.c.v. delivery of ACCS improved motor outcome but failed to improve cognitive outcome or tissue sparing. Importantly, only i.c.v. ACCS treatment produced persistent motor improvements at a later endpoint. The i.c.v. ACCS treatment significantly reduced PBBI-induced increase in @entity6 ( @entity6 ) and ionized @entity3 binding adaptor molecule 1 ( @entity7 ) expression. Concomitant reduction of both @entity7 and @entity4 staining were detected in corpus callosum with i.c.v. ACCS treatment. Conclusions: ACCS, as a treatment for @entity1 , showed promise with regard to functional (motor) recovery and demonstrated strong capability to modulate neuroinflammatory responses that may underline functional recovery. However, the majority of beneficial effects appear restricted to the i.c.v. route of ACCS delivery, which warrants future studies examining delivery routes (e.g. intranasal delivery) which are more clinically viable for the treatment of @entity1 .

title: Treatment with amnion-derived cellular cytokine solution (ACCS) induces persistent motor improvement and ameliorates neuroinflammation in a XXXX model of penetrating ballistic-like @entity5 .

answer: @entity0


abstract: A 30-year-old @entity0 developed chills, cough and @entity6 a few minutes after using a fluoropolymer-based waterproofing spray in a small closed room. He visited our hospital 1  h later. Examination revealed that the @entity0 had incessant cough, @entity9 , @entity2 and decreased peripheral arterial @entity1 saturation. Blood tests revealed @entity3 with elevated serum @entity7 levels. Chest radiographs and computed tomography (CT) scan showed bilateral ground glass opacities, mainly in the upper lobes. Bronchoalveolar lavage (BAL) fluid obtained from the right middle lobe showed a bloody appearance. Microscopic examination of a BAL cytospin specimen revealed the presence of numerous red blood cells associated with extreme @entity8 . Microbiological studies of the BAL fluid were negative. The @entity0 was observed without corticosteroid therapy, and his symptoms and abnormal shadows on the chest radiographs and CT improved. On day 7 after admission, the @entity0 was discharged from the hospital. Accidental inhalation of waterproofing spray may cause @entity4 , a rare manifestation of @entity5 . Supportive treatment may be effective and sufficient.

title: XXXX after use of a fluoropolymer-based waterproofing spray.

answer: @entity4


abstract: OBJECTIVES: To investigate the effects of botulinum A toxin in treating @entity0 with @entity1 due to detrusor underactivity. METHODS: Twenty @entity0 with chronic urinary retention (n = 13) or severe @entity5 (n = 7) received 50 U of botulinum A toxin by urethral injection. The clinical effects, obstructive symptom score, quality-of-life index, and urodynamics were compared at baseline and after treatment. RESULTS: Of the 4 males and 16 females (age range 14 to 86 years) with @entity1 ( @entity3 in 5, @entity1 in 5, @entity2 in 6, and detrusor failure of unknown origin in 4), 18 (90%) were treated satisfactorily. Among these @entity0 , the mean quality-of-life score decreased significantly from 5.68 +/- 0.67 to 1.16 +/- 1.61. The median voiding pressure (56.5 +/- 41.2 versus 39.0 +/- 38.4 cm @entity4 ) decreased significantly, as did the maximal urethral closure pressure (65.5 +/- 38.1 versus 50 +/- 32.1 cm @entity4 ) and residual urine volume (300 +/- 189.1 versus 50 +/- 153.6 mL) at 2 weeks after treatment and remained stationary for 3 months. The subjective maximal effect was achieved within 1 to 2 weeks. In 7 @entity0 , the indwelling catheters were removed, and in 4 @entity0 who performed clean intermittent self-catheterization, the frequency decreased or it was discontinued. The other 7 @entity0 with difficult urination had significant improvement in the obstructive symptom score (18 +/- 3.3 versus 7 +/- 4.5, P = 0.000). CONCLUSIONS: Botulinum A toxin at a dose of 50 U was effective in reducing urethral sphincter resistance among our @entity0 with detrusor underactivity and difficult urination.

title: Effect of botulinum a toxin in the treatment of XXXX due to detrusor underactivity.

answer: @entity1


abstract: BACKGROUND: The purpose of this study was to assess the relationship between changes in @entity1 ( @entity1 ) during @entity2 ( @entity2 ) and the peripheral changes in blood pressure (BP) and sympathetic nerve activity (SNA) in @entity0 subjects. We hypothesized that @entity0 with no @entity1 shortening during @entity2 have a vasovagal-like response with a greater decrease in BP and SNA when compared to @entity0 with @entity1 shortening. METHODS: @entity1 , BP, and SNA recordings were attempted in 24 @entity0 undergoing the implantation of a dual-chamber implantable defibrillator. Changes were measured during the first 5 seconds of @entity2 and compared with the 5 seconds prior to @entity2 induction. RESULTS: @entity1 shortened during @entity2 in nine @entity0 (mean%   @entity1 = -12    8%) and remained unchanged or lengthened in seven @entity0 (mean%   @entity1 = 7    7%). Eight @entity0 had ventriculoatrial (VA) conduction prohibiting assessment of @entity1 changes. In @entity0 with @entity1 shortening, the %   MBP (mean BP) was -47    6% compared to -58    8% in @entity0 with no @entity1 shortening (P < 0.01). In @entity0 with VA conduction, the %   MBP was -54    3%. SNA recordings were successfully obtained in four @entity0 . When compared to baseline, SNA increased by 34    30% in two @entity0 with @entity1 shortening, decreased by 25% in one @entity0 with @entity1 lengthening, and by 90% in the fourth @entity0 with VA conduction. CONCLUSIONS: We have shown that @entity0 with no @entity1 shortening have a significantly greater decrease in MBP during @entity2 when compared to @entity0 with @entity1 shortening. The underlying mechanism appears to be reflex mediated with a vasovagal-like response in @entity0 with no @entity1 shortening.

title: "Vasovagal" Response during XXXX : Incidence and Implications.

answer: @entity2


abstract: BACKGROUND: Gastrointestinal (GI) @entity6 is an important and sometimes serious complication in critically ill neurological @entity0 who suffered from @entity2 and @entity5 and those in intensive care. There is no study evaluating frequency, severity and risk factors of @entity4 in @entity0 with primary @entity8 ( @entity8 ). AIMS: To evaluate the frequency, severity and predictors of @entity4 in @entity0 with @entity8 . METHODS: In a prospective hospital-based study, consecutive CT-proven @entity8 @entity0 within 10 days of the ictus were included. The @entity0 with history of peptic ulcer, @entity4 , @entity1 , @entity6 diathesis and those on antiplatelet, anticoagulant or nonsteroidal antiinflammatory drugs (NSAIDS) were excluded. A detailed neurological evaluation was carried out. Glasgow @entity7 scale (GCS) was used for assessment of consciousness level and Canadian neurological scale (CNS) for severity of @entity2 . The haematomas were classified into small (<20 ml), medium (20-40 ml) and large (>40 ml). The occurrence of @entity4 during 14 days of ictus was considered due to @entity8 . To evaluate the predictors of @entity4 , various clinical and CT scan findings were evaluated by univariate followed by multivariate logistic regression analysis. RESULTS: Fifty-one @entity0 with @entity8 were included whose age ranged between 30 and 80 years and 14 were female. The mean GCS score was 8.9 (3-15) and CNS score was 2.2 (2-4). Haematoma was small (<20 ml) in 11 @entity0 and medium (20-40 ml) and large (>40 ml) in 20 @entity0 each. Evidences of @entity3 were present in 20 @entity0 . @entity6 ( @entity6 ) was noted in 15 @entity0 which was more than 40 ml in 4 @entity0 and one of these @entity0 needed blood transfusion. On univariate analysis, the size of haematoma, @entity3 , motor signs on the nonhemiplegic side and pupillary asymmetry were significantly related to @entity4 . On multivariate analysis, the best set of predictors of @entity6 included size of haematoma, @entity3 and GCS score. CONCLUSION: @entity4 is more likely present in @entity0 with larger haematoma having @entity3 . Our study highlights the importance of @entity3 , which is an important and modifiable risk factor for @entity4 in @entity8 @entity0 .

title: Predictors of XXXX in acute @entity8 .

answer: @entity4


abstract: BACKGROUND: Gastrointestinal (GI) @entity6 is an important and sometimes serious complication in critically ill neurological @entity0 who suffered from @entity2 and @entity5 and those in intensive care. There is no study evaluating frequency, severity and risk factors of @entity4 in @entity0 with primary @entity8 ( @entity8 ). AIMS: To evaluate the frequency, severity and predictors of @entity4 in @entity0 with @entity8 . METHODS: In a prospective hospital-based study, consecutive CT-proven @entity8 @entity0 within 10 days of the ictus were included. The @entity0 with history of peptic ulcer, @entity4 , @entity1 , @entity6 diathesis and those on antiplatelet, anticoagulant or nonsteroidal antiinflammatory drugs (NSAIDS) were excluded. A detailed neurological evaluation was carried out. Glasgow @entity7 scale (GCS) was used for assessment of consciousness level and Canadian neurological scale (CNS) for severity of @entity2 . The haematomas were classified into small (<20 ml), medium (20-40 ml) and large (>40 ml). The occurrence of @entity4 during 14 days of ictus was considered due to @entity8 . To evaluate the predictors of @entity4 , various clinical and CT scan findings were evaluated by univariate followed by multivariate logistic regression analysis. RESULTS: Fifty-one @entity0 with @entity8 were included whose age ranged between 30 and 80 years and 14 were female. The mean GCS score was 8.9 (3-15) and CNS score was 2.2 (2-4). Haematoma was small (<20 ml) in 11 @entity0 and medium (20-40 ml) and large (>40 ml) in 20 @entity0 each. Evidences of @entity3 were present in 20 @entity0 . @entity6 ( @entity6 ) was noted in 15 @entity0 which was more than 40 ml in 4 @entity0 and one of these @entity0 needed blood transfusion. On univariate analysis, the size of haematoma, @entity3 , motor signs on the nonhemiplegic side and pupillary asymmetry were significantly related to @entity4 . On multivariate analysis, the best set of predictors of @entity6 included size of haematoma, @entity3 and GCS score. CONCLUSION: @entity4 is more likely present in @entity0 with larger haematoma having @entity3 . Our study highlights the importance of @entity3 , which is an important and modifiable risk factor for @entity4 in @entity8 @entity0 .

title: Predictors of @entity4 in acute XXXX .

answer: @entity8


abstract: DESIGN: Retrospective cohort study. SETTING: Major international tertiary care referral center for @entity1 repair. @entity0 : One hundred thirty-eight @entity0 at the @entity0 's Hospital of Philadelphia who had palate repair performed between 2010 and 2013, excluding syndromic @entity0 , @entity0 undergoing palate revision, and @entity0 with incomplete payment information. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Fees and charges for procedures. RESULTS: Surgeon payment was significantly higher for international adoptees (   =  2047.51 [ 128.35 to  3966.66], P = .038). Medicaid-adjusted surgeon payments averaged  1006 more for adoptees ([- 394.19 to  2406.98], P = .158). CONCLUSIONS: Hospital and anesthesiology costs for adoptee palate repair were highly variable but did not differ significantly from those for nonadoptees. Partly due to payer mix, surgeon reimbursement was somewhat higher for international adoptees. No difference in total payment was found.

title: Economic Analysis of XXXX Repair in International Adoptees.

answer: @entity1


abstract: UNASSIGNED: Genome-wide DNA hypomethylation is an early event in the carcinogenic process. Percent methylation of long interspersed @entity7 element-1 (LINE-1) is a biomarker of genome-wide methylation and is a potential biomarker for @entity0 . Understanding factors associated with percent LINE-1 DNA methylation in histologically normal tissues could provide insight into early stages of @entity3 . In a cross-sectional study of 121 healthy @entity1 with no prior history of @entity2 who underwent reduction mammoplasty, we examined associations between plasma and breast @entity6 , genetic variation in one- @entity5 metabolism, and percent LINE-1 methylation using multivariable regression models (adjusting for race, oral contraceptive use, and @entity4 use). Results are expressed as the ratio of LINE-1 methylation relative to that of the referent group, with the corresponding 95% confidence intervals (CI). We found no significant associations between plasma or breast @entity6 and percent LINE-1 methylation. Variation in @entity9 , MTR, and @entity8 were significantly associated with percent LINE-1 methylation. Variant allele carriers of @entity9 @entity12 had 4% lower LINE-1 methylation (Ratio 0.96, 95% CI 0.93-0.98), while variant allele carriers of MTR @entity11 (Ratio 1.03, 95% CI 1.01-1.06) and @entity8 @entity10 (Ratio 1.03, 95% CI 1.01-1.06) had 3% higher LINE-1 methylation, compared to those carrying the more common genotypes of these SNPs. DNA methylation of LINE-1 elements in histologically normal breast tissues is influenced by polymorphisms in genes in the one- @entity5 metabolism pathway. Future studies are needed to investigate the sociodemographic, environmental and additional genetic determinants of DNA methylation in breast tissues and the impact on @entity0 susceptibility.

title: Associations between genetic variation in one- XXXX metabolism and LINE-1 DNA methylation in histologically normal breast tissues.

answer: @entity5


abstract: UNASSIGNED: In this study, we investigate whether the provision of biologic therapy for @entity1 is equitable across South Asian and English groups in NHS Trusts, which serve areas with significant ethnic variation. Data were requested from 10 NHS Trusts using a Freedom of Information (FOI) approach. Details of numbers of @entity0 by ethnicity treated with infliximab or adalumimab for @entity1 between 2010 and 2012 were requested. Using population-based estimates of disease prevalence and Census data on population structure, observed and expected numbers who should have received treatment were calculated. In three Trusts, the number of South Asian @entity0 who received such treatment was significantly less than British/White @entity0 . These were: Pennine Acute Hospitals NHS Trust covering Oldham and North Manchester, Barking, Havering _ Redbridge University Hospitals NHS Trust and University Hospitals of @entity2 Trust. The study is limited by several factors: The only data available on prevalence in both English and South Asian communities comes from Leicester and was published in 1993. More recent data suggests that the prevalence of @entity1 now approaches 150/10(5) compared to the 76/10(5) for English @entity0 which was recorded in Leicester. However, the two subsequent studies on prevalence which were published in 2000 from the North of England and 2010 from Scotland do not provide a breakdown by ethnicity. The data were collected by administrative staff using a variety of approaches to their Trust's data bases and so the techniques used in each Trust are not comparable. In addition, studies from elsewhere suggest that the quality of FOI data is affected by the motivation of staff who collect the data. With the exception of Leicester, there was no quality check on the accuracy of the data. In Leicester, 139 @entity0 were on a register of biologic therapy and this compared with 343 @entity0 reported by the FOI request. However, the proportions of @entity0 by type of treatment and by ethnicity were comparable in the two data sets. This suggests that the data on ethnic differences reported by the FOI study reflects real differences. Clearly, there are South Asian communities where @entity0 with @entity1 appear not to receive appropriate treatment in the form of biologics, and the reasons behind this need further consideration and investigation. We need to develop robust methods of monitoring the provision of biologic therapy across ethnic groups and communities. It is unacceptable for there to be a difference based on such grounds.

title: Ethnic variations in the provision of biologic therapy for XXXX : a Freedom of Information study.

answer: @entity1


abstract: BACKGROUND: Chronic @entity4 is highly prevalent worldwide. PRIMARY STUDY OBJECTIVE: The aim of this study was to evaluate the efficacy of Helical(  ) microcoils, a new, noninvasive treatment for chronic @entity4 . DESIGN: This was a prospective, observational study. SETTING: The study was conducted at the main author's private clinic, in S  o Paulo, Brazil. @entity0 : We evaluated 20 physicians, from 2 different hospitals, who suffered from chronic @entity4 and volunteered to participate in the study. INTERVENTION: The Helical(  ) microcoils were applied to the skin over the affected areas. Before and after the intervention, the physician- @entity0 completed questionnaires and a visual analog scale. PRIMARY OUTCOME MEASURES: We quantified postintervention improvement or worsening of @entity3 and @entity2 . RESULTS: Significant improvements in @entity3 and @entity2 were observed in 95% of the physician- @entity0 evaluated. The only side effect reported was mild @entity1 at the application site, which occurred in 5 of the 20 cases. CONCLUSION: The use of Helical microcoils was found to be safe and efficacious in relieving @entity2 and @entity3 .

title: Cutaneous Application of Silicone Wafers Containing Carbon Microcoils: Efficacy in Relieving Chronic Muscle Tension and XXXX .

answer: @entity3


abstract: UNASSIGNED: Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200    g   @entity4 ), and short-term BP variability ( @entity6 ), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential @entity2 with normal estimated glomerular filtration rate (>60   ml   @entity4 ) per 1.73   m(2)), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (26%) @entity0 . ARV of 24-h systolic BP (SBP) was significantly higher in @entity0 with MAU (9.8 (8.5-11.1) mm   Hg) when compared with those without it (9.1 (8-10.2) mm   Hg; P=0.007). This difference held (P=0.026) after adjustment for age, mean levels of BP and other potential confounders by analysis of covariance. A statistically significant correlation was also found between ARV of 24-h SBP and uAER (r=0.17; P=0.003). This association remained significant (b=0.15; P=0.01), also taking into account the effect of 24-h average systolic and diastolic BP, age, gender, @entity1 , serum @entity3 , @entity5 , estimated glomerular filtration rate in multiple regression analyses. All the other indices of short-term @entity6 tested were not independently associated with MAU. Our results seem to suggest that in essential @entity2 , short-term @entity6 , only when estimated by ARV of 24-h SBP, is independently associated with MAU.Journal of @entity0 @entity2 advance online publication, 18 June 2015; doi:10.1038/jhh.2015.66.

title: Average real variability of 24-h systolic blood pressure is associated with microalbuminuria in @entity0 with primary XXXX .

answer: @entity2


abstract: UNASSIGNED: Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200    g   @entity4 ), and short-term BP variability ( @entity6 ), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential @entity2 with normal estimated glomerular filtration rate (>60   ml   @entity4 ) per 1.73   m(2)), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (26%) @entity0 . ARV of 24-h systolic BP (SBP) was significantly higher in @entity0 with MAU (9.8 (8.5-11.1) mm   Hg) when compared with those without it (9.1 (8-10.2) mm   Hg; P=0.007). This difference held (P=0.026) after adjustment for age, mean levels of BP and other potential confounders by analysis of covariance. A statistically significant correlation was also found between ARV of 24-h SBP and uAER (r=0.17; P=0.003). This association remained significant (b=0.15; P=0.01), also taking into account the effect of 24-h average systolic and diastolic BP, age, gender, @entity1 , serum @entity3 , @entity5 , estimated glomerular filtration rate in multiple regression analyses. All the other indices of short-term @entity6 tested were not independently associated with MAU. Our results seem to suggest that in essential @entity2 , short-term @entity6 , only when estimated by ARV of 24-h SBP, is independently associated with MAU.Journal of @entity0 @entity2 advance online publication, 18 June 2015; doi:10.1038/jhh.2015.66.

title: Average real variability of 24-h systolic blood pressure is associated with microalbuminuria in XXXX with primary @entity2 .

answer: @entity0


abstract: @entity2 ( @entity2 ) is an established and successful procedure. However, the design of prostheses continues to be modified in an attempt to optimise the functional outcome of the @entity0 . The aim of this study was to determine if @entity0 outcome after @entity2 was influenced by the design of the prosthesis used. A total of 212 @entity0 (mean age 69; 43 to 92; 131 female (62%), 81 male (32%)) were enrolled in a single centre double-blind trial and randomised to receive either a Kinemax (group 1) or a Triathlon (group 2) @entity2 . @entity0 were assessed pre-operatively, at six weeks, six months, one year and three years after surgery. The outcome assessments used were the Oxford Knee Score; range of movement; @entity1 numerical rating scales; lower limb power output; timed functional assessment battery and a satisfaction survey. Data were assessed incorporating change over all assessment time points, using repeated measures analysis of variance longitudinal mixed models. Implant group 2 showed a significantly greater range of movement (p = 0.009), greater lower limb power output (p = 0.026) and reduced report of 'worst daily @entity1 ' (p = 0.003) over the three years of follow-up. Differences in Oxford Knee Score (p = 0.09), report of 'average daily @entity1 ' (p = 0.57) and timed functional performance tasks (p = 0.23) did not reach statistical significance. Satisfaction with outcome was significantly better in group 2 (p = 0.001). These results suggest that @entity0 outcome after @entity2 can be influenced by the prosthesis used.

title: Implant design influences XXXX outcome after total knee arthroplasty: a prospective double-blind randomised controlled trial.

answer: @entity0


abstract: A poor response to chemotherapy ( <= 90% @entity1 ) for @entity2 leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over @entity3 ( @entity3 ) with narrow margins in @entity0 who respond poorly to chemotherapy. We only analysed @entity0 with an @entity2 of the limb, a poor response to chemotherapy and close margins on @entity3 (marginal/intralesional) or primary amputation: 360 @entity0 (36 @entity3 (intralesional margins), 197 @entity3 (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following @entity3 with intralesional margins, and 39 (20%) following @entity3 with marginal margins. There was no local recurrence in @entity0 who underwent amputation. The five-year survival for all @entity0 was 41% (95% confidence interval (CI) 35 to 46), but for those treated by @entity3 with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by @entity3 with intralesional margins. @entity0 who had @entity3 and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 @entity0 but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over @entity3 with marginal margins in these @entity0 with a poor overall prognosis. Cite this article: Bone Joint J 2015;97-B:115-20.

title: Does amputation offer any survival benefit over limb salvage in XXXX @entity0 with poor chemonecrosis and close margins?

answer: @entity2


abstract: A poor response to chemotherapy ( <= 90% @entity1 ) for @entity2 leads to poorer survival and an increased risk of local recurrence, particularly if there is a close margin of excision. We evaluated whether amputation confers any survival benefit over @entity3 ( @entity3 ) with narrow margins in @entity0 who respond poorly to chemotherapy. We only analysed @entity0 with an @entity2 of the limb, a poor response to chemotherapy and close margins on @entity3 (marginal/intralesional) or primary amputation: 360 @entity0 (36 @entity3 (intralesional margins), 197 @entity3 (marginal margins) and 127 amputations) were included. Local recurrence developed in 13 (36%) following @entity3 with intralesional margins, and 39 (20%) following @entity3 with marginal margins. There was no local recurrence in @entity0 who underwent amputation. The five-year survival for all @entity0 was 41% (95% confidence interval (CI) 35 to 46), but for those treated by @entity3 with marginal margins was 46.2% (95% CI 38 to 53), 36.3% (95% CI 27 to 45) for those treated by amputation, and 28% (95 CI 14 to 44) for those treated by @entity3 with intralesional margins. @entity0 who had @entity3 and then developed local recurrence as a first event had the same survival as those who had primary amputation without local recurrence. Prophylactic adjuvant radiotherapy was used in 40 @entity0 but had no discernible effect in preventing local recurrence. Although amputation offered better local control, it conferred no clear survival benefit over @entity3 with marginal margins in these @entity0 with a poor overall prognosis. Cite this article: Bone Joint J 2015;97-B:115-20.

title: Does amputation offer any survival benefit over limb salvage in @entity2 XXXX with poor chemonecrosis and close margins?

answer: @entity0


abstract: PURPOSE: Although survival rates have improved for @entity0 with bulky and advanced-stage @entity9 ( @entity9 ), current treatments entail substantial acute morbidity and risks for late effects such as @entity6 , second @entity1 , and @entity3 . A novel, brief chemotherapy regimen ( @entity7 , @entity16 , @entity15 , @entity12 , @entity11 , @entity13 , and @entity5 [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, @entity7 , and @entity11 , and maintain dose-intensity (DI). This brief chemotherapy was combined with @entity10 ( @entity10 ) to bulky disease sites. METHODS: Since May 1989, 65 previously untreated @entity0 were treated for stage II @entity9 with bulky mediastinal involvement (n = 21) or for stage III or IV @entity9 (n = 44). @entity0 received weekly chemotherapy for 12 weeks. Consolidative @entity10 was given to the first 25 @entity0 to sites of @entity2 or @entity8 that persisted after chemotherapy; in the remaining 40 @entity0 , @entity10 was limited to bulky disease ( @entity14 > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]). RESULTS: With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II @entity0 with bulky mediastinal disease and 82% for @entity0 with stage III to IV disease. There were no treatment-related @entity4 . In a preliminary analysis on a subset of @entity0 , female and male fertility appears to be preserved. CONCLUSION: These preliminary results indicate that the Stanford V chemotherapy regimen with or without @entity10 is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage @entity9 . Less cumulative exposure to alkylating agents, @entity7 , and @entity11 and limited use of radiation is expected to decrease risks for second @entity1 and late cardiopulmonary @entity3 . Based on these results, the Stanford V chemotherapy with or without @entity10 regimen deserves further study in the context of a randomized clinical trial.

title: Brief chemotherapy, Stanford V, and adjuvant radiotherapy for bulky or advanced-stage XXXX : a preliminary report.

answer: @entity9


abstract: PURPOSE: Scintigraphic flare in association with response to therapy has been well described in the medical literature. During the course of a recent @entity0 trial, it became apparent that several @entity1 with worsening bone scan but no other clinical evidence of disease progression might have potentially benefited from continued therapy, but had therapy discontinued. A retrospective analysis of this issue was performed to assess the magnitude and scope of this problem. MATERIALS AND METHODS: A total of 648 @entity1 with hormone receptor-positive or unknown @entity0 were treated as part of a large-scale trial of first-line hormonal therapy. @entity1 were assessed for response to therapy, including response duration, progression-free interval (PFI), overall survival, and quality of life. The retrospective analysis presented here was performed to assess whether @entity1 with a possible scintigraphic flare within the first 16 weeks of therapy might have had therapy discontinued prematurely due to a worsening bone scan attributable to @entity2 flare, rather than due to disease progression. RESULTS: Analysis of the hormonal trial showed that of 376 assessable @entity1 108 (29%) with @entity3 had a possible scintigraphic flare by week 8 or 16 of the trial, based on data on the case report forms and radiology reports (bone scans and x-rays). Of these, 69 @entity1 (64%) were continued on study therapy, which resulted in clinical benefit in 50 (72%) of those @entity1 . In contrast, 39 @entity1 (36%) with possible scintigraphic flare were removed from the trial. CONCLUSION: We conclude that changes in bone scintigraphy that mimic progressive disease early in the course of hormonal treatment of @entity1 with @entity0 metastatic to bone may represent scintigraphic flare associated with response. Thus, clinicians must be cognizant of the phenomenon of scintigraphic flare to avoid premature discontinuation of a potentially beneficial treatment.

title: Worsening bone scan in the evaluation of antitumor response during hormonal therapy of XXXX .

answer: @entity0


abstract: @entity7 ( @entity7 ) status is the most important prognostic factor for localized @entity3 . Usually, @entity0 with Breslow thickness of less than 1.0 mm are not included in @entity7 protocols. However, the literature presents a rate ranging from 3 to 7% of nodal recurrence in thin @entity3 . Ulceration, regression and high mitotic rate have been considered to be indications for an @entity7 biopsy. The metastatic potential of the vertical growth phase is uncertain. To correlate pathological features in thin @entity3 with @entity7 @entity1 , we reviewed 358 @entity0 submitted to @entity7 biopsy. Seventy-seven @entity0 with lesions of 1 mm or smaller were included in the study group. Histological evaluation of the @entity2 included thickness, Clark level, mitotic rate, @entity4 , regression, and growth phase. Lymphoscintigraphy was performed on all @entity0 . Lymphatic mapping and gamma probe detection were both used for @entity7 biopsy. Histological examination of @entity7 consisted of @entity5 - @entity6 and immunohistochemical staining. Median follow-up was 37 months. Six @entity0 had micrometastases. Statistical analysis by the Fisher test showed that @entity4 (P = 0.019), high mitotic rate (P = 0.008) and vertical growth phase (P = 0.002) were positively correlated with micrometastases. If other studies confirm these results, more @entity3 @entity0 must be submitted to @entity7 biopsy.

title: Vertical growth phase and positive sentinel node in thin XXXX .

answer: @entity3


abstract: There are few population-based studies of @entity1 and none conducted in developing countries. In the present study the prevalence and predictors of elevated serum @entity6 levels (SCr > or = 1.3 mg/dl for @entity0 and 1.1 mg/dl for @entity0 ) were determined among Brazilian adults (18-59 years) and older adults (>60 years). @entity0 included all older adults (N = 1742) and a probabilistic sample of adults (N = 818) from Bambu town, MG, Southeast Brazil. Predictors were investigated using multiple logistic regression. Mean SCr levels were 0.77 +/- 0.15 mg/dl for adults, 1.02 +/- 0.39 mg/dl for older @entity0 , and 0.81 +/- 0.17 mg/dl for older @entity0 . Because there were only 4 cases (0.48%) with elevated SCr levels among adults, the analysis of elevated SCr levels was restricted to older adults. The overall prevalence of elevated SCr levels among the elderly was 5.09% (76/1494). The prevalence of hypercreatinemia increased significantly with age (chi = 26.17, P = 0.000), being higher for older @entity0 (8.19%) than for older @entity0 (5.29%, chi = 5.00, P = 0.02). Elevated SCr levels were associated with age 70-79 years (odds ratio [OR] = 2.25, 95% confidence interval [CI]: 1.15-4.42), @entity2 (OR = 3.04, 95% CI: 1.34-6.92), use of antihypertensive drugs (OR = 2.46, 95% CI: 1.26-4.82), @entity5 (OR = 3.37, 95% CI: 1.31-8.74), and @entity4 (OR = 3.43, 95% CI: 1.30-9.09) among @entity0 , and with age >80 years (OR = 4.88, 95% CI: 2.24-10.65), use of antihypertensive drugs (OR = 4.06, 95% CI: 1.67-9.86), physical inactivity (OR = 2.11, 95% CI: 1.11-4.02) and @entity3 (OR = 3.89, 95% CI: 1.58-9.62) among @entity0 . The prevalence of @entity1 observed was much lower than that reported in other population-based studies, but predictors were similar. New investigations are needed to confirm the variability in prevalence and associated factors of @entity1 among populations.

title: XXXX based on serum @entity6 levels in a Brazilian community: the Bambu   Health and Ageing Study.

answer: @entity1


abstract: There are few population-based studies of @entity1 and none conducted in developing countries. In the present study the prevalence and predictors of elevated serum @entity6 levels (SCr > or = 1.3 mg/dl for @entity0 and 1.1 mg/dl for @entity0 ) were determined among Brazilian adults (18-59 years) and older adults (>60 years). @entity0 included all older adults (N = 1742) and a probabilistic sample of adults (N = 818) from Bambu town, MG, Southeast Brazil. Predictors were investigated using multiple logistic regression. Mean SCr levels were 0.77 +/- 0.15 mg/dl for adults, 1.02 +/- 0.39 mg/dl for older @entity0 , and 0.81 +/- 0.17 mg/dl for older @entity0 . Because there were only 4 cases (0.48%) with elevated SCr levels among adults, the analysis of elevated SCr levels was restricted to older adults. The overall prevalence of elevated SCr levels among the elderly was 5.09% (76/1494). The prevalence of hypercreatinemia increased significantly with age (chi = 26.17, P = 0.000), being higher for older @entity0 (8.19%) than for older @entity0 (5.29%, chi = 5.00, P = 0.02). Elevated SCr levels were associated with age 70-79 years (odds ratio [OR] = 2.25, 95% confidence interval [CI]: 1.15-4.42), @entity2 (OR = 3.04, 95% CI: 1.34-6.92), use of antihypertensive drugs (OR = 2.46, 95% CI: 1.26-4.82), @entity5 (OR = 3.37, 95% CI: 1.31-8.74), and @entity4 (OR = 3.43, 95% CI: 1.30-9.09) among @entity0 , and with age >80 years (OR = 4.88, 95% CI: 2.24-10.65), use of antihypertensive drugs (OR = 4.06, 95% CI: 1.67-9.86), physical inactivity (OR = 2.11, 95% CI: 1.11-4.02) and @entity3 (OR = 3.89, 95% CI: 1.58-9.62) among @entity0 . The prevalence of @entity1 observed was much lower than that reported in other population-based studies, but predictors were similar. New investigations are needed to confirm the variability in prevalence and associated factors of @entity1 among populations.

title: @entity1 based on serum XXXX levels in a Brazilian community: the Bambu   Health and Ageing Study.

answer: @entity6


abstract: 1. A @entity4 protein similar to erabutoxins a and b of Laticauda semifasciata was isolated in crystalline form from the venoms of Laticauda laticaudata and Laticauda colubrina. The name ;laticotoxin a' is proposed. 2. Laticotoxin a is homogeneous by CM-cellulose column chromatography, disc electrophoresis and ultracentrifugation and by terminal @entity1 analyses. 3. Laticotoxin a consists of 62 @entity1 residues. The molecular weight by ultracentrifuging is 6520. 4. The minimal 50% lethal dose of laticotoxin a by intramuscular injection to @entity0 is 0.13mug./g. body wt. The toxin attacks the postsynaptic membrane, competing with @entity2 . 5. Radioactive @entity3 are incorporated into laticotoxin a in vivo. The incorporation is inhibited by @entity5 , suggesting that the biosynthesis of the toxin follows the mechanism of protein biosynthesis, although the toxin molecule is rather small as a protein.

title: Properties and biosynthesis of a XXXX protein of the venoms of s snakes Laticauda laticaudata and Laticauda colubrina.

answer: @entity4


abstract: PURPOSE: @entity4 ( @entity4 ) screening among @entity0 with newly diagnosed @entity2 can decrease mortality in their affected first-degree relatives. In Germany, it is not yet clinical practice and the cost-effectiveness of different testing strategies is unknown. METHODS: We developed a decision-analytic model to analyze the cost-effectiveness of @entity4 screening from the perspective of the German Statutory Health Insurance system. A total of 22 testing strategies considering family-history assessment, analysis of @entity1 samples (i.e., immunohistochemistry (IHC), microsatellite instability, and @entity3 mutation testing) and genetic sequencing were analyzed. Life-years gained in relatives by closed-meshed colonoscopy and aspirin prophylaxis were estimated by Markov models. Uncertainty was assessed deterministically and probabilistically. RESULTS: On average, detected mutation carriers gained 0.52 life-years (undiscounted: 1.34) by increased prevention. Most strategies were dominated, with three exceptions: family assessment by the Bethesda criteria followed by IHC and @entity3 testing and genetic sequencing; IHC and @entity3 testing and genetic sequencing; and direct sequencing of all index @entity0 . Their incremental cost-effectiveness was [ @entity5 ]77,268, [ @entity5 ]253,258, and [ @entity5 ]4,188,036 per life-year gained, respectively. CONCLUSION: The results were less favorable than those of previous models. Chemoprevention appears to provide comparably low additional benefit and improves cost-effectiveness only slightly.

title: Economic evaluation of genetic screening for XXXX in Germany.

answer: @entity4


abstract: BACKGROUND: Accurate diagnosis of @entity3 ( @entity3 ) is of paramount importance in @entity0 management which necessitates the development of efficient as well as accurate diagnostic methods. Q wave is not present in all @entity0 with @entity3 and its prevalence is declining. Recently, fragmented QRS (Fqrs) complex has been introduced as a marker of prior @entity3 . In this study, we intended to investigate diagnostic value of fQRS compared to Q wave. METHODS: We included 500 consecutive @entity0 with known or suspected @entity2 ( @entity2 ) who underwent two days gated myocardial perfusion imaging (MPI) using Dipyridamole pharmacologic stress. ECG was evaluated to detect fQRS as well as Q-Wave. Finally, subjects were compared in terms of ventricular perfusion and function indices. RESULTS: 207 @entity0 and 269 @entity0 with mean age of 57.06  12 years were studied. ECG analysis showed that 14.3% of the @entity0 had both fQRS and Q waves, 30.7% had fQRS and 3.8% had Q waves. Fixed myocardial perfusion defect was noted in 22.3% of @entity0 according to MPIs. Sensitivity, specificity, positive and negative predictive values for @entity1 detection were 78%, 65%, 39% and 91% respectively for fQRS and 61%, 94% , 76% and 89% for Q wave. CONCLUSIONS: Although fQRS had lower specificity compared to Q wave in the detection of @entity1 , due to higher sensitivity and negative predictive value can be an invaluable diagnostic index. There is also an incremental value for fQRS in association with Q-wave in @entity1 assessment.

title: Comparison between fragmented QRS versus Q wave in XXXX detection using myocardial perfusion single photon emission computed tomography.

answer: @entity1


abstract: Objectives. To explore the correlation of serum IgG4 (sIgG4) with clinical manifestations or therapeutic response in @entity1 ( @entity1 ). Methods. Consecutive 136 @entity1 @entity0 were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 @entity1 @entity0 were stained immunohistochemically for IgG4. Results. Forty-six percent of 136 @entity1 @entity0 had elevated sIgG4. @entity0 with elevated sIgG4 had higher sIgG4/sIgG ratio, @entity4 , erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all P < 0.05). Among 45 @entity0 who received @entity3 and @entity7 therapy, 50% (9/18) of @entity0 with elevated sIgG4 and 85% (23/27) of @entity0 with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (   (2) = 6.508, P = 0.011). IgG4-positive plasma cell count correlated positively with sIgG4, total @entity2 score, and CD3-, @entity5 -, and @entity6 -positive cell counts (all P < 0.05). Conclusions. Our results showed that elevated sIgG4 in @entity1 is common and disproportional to total IgG and @entity1 with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to @entity3 and @entity7 therapy.

title: Elevated Serum IgG4 Defines Specific Clinical Phenotype of XXXX .

answer: @entity1


abstract: @entity7 ( @entity7 ) is a relatively common @entity6 manifested by low platelet count due to immune-mediated @entity5 and/or suppression of platelet production. This study aim was to evaluate characteristics and clinical presentation of adult @entity0 with @entity7 and exploring the clinical value of platelet antibodies assay in proposed cases in Iranian population. In this prospective case series 46 adult @entity0 with @entity7 and platelet count of  <100  *  10(9)/L, referred to the Taleghani Medical Center, Tehran, Iran between 2007 and 2009 were evaluated. There were 26 females and 20 males (1.3:1) with mean age of 38.9      19.7  years. The platelet autoantibodies were measured by means of indirect platelet suspension immunofluorescence test. According to our results, 7 @entity0 (15.2  %) displayed a positive platelet antibody assay. There was a significant negative correlation between platelet count and antibody level (r  =  -0 0.59; p  <  0.001). Additionally, a positive correlation between platelet count and @entity0 ' age (r  =  0.302; p  =  0.042) was detected. 20 @entity0 (56.5  %) were symptomatic at presentation and the most common @entity1 signs were @entity8 , @entity8 and @entity4 . Results indicated no significant correlation between increased platelet antibody level and @entity1 manifestations except for @entity2 (r  =  0.435; p  =  0.02) and @entity4 (r  =  0.382; p  =  0.015). Disclosure of platelet autoantibodies and the consequential @entity3 associated to some extent but not completely with the propensity to bleed which necessitates more factors to be evaluated.

title: Clinical significance of positive platelet immunofluorescence assay in adult immune XXXX .

answer: @entity3


abstract: The hormonal regulation of sex differences in electrocommunicatory behavior and brain substance P-like immunoreactivity ( @entity2 -ir) were examined in the weakly electric fish, Apteronotus leptorhynchus. This animal modulates its electric organ discharge (EOD) to produce discrete electric social signals (chirps), which function in @entity0 . Males readily chirp in response to electrosensory stimuli that mimic the presence of a conspecific; females also chirp in response to such stimuli, but do so at much lower rates than males. We have recently demonstrated that @entity1 treatment enhances chirping behavior in females and may also lead to a change in chirp quality or structure. In this study, we quantified @entity1 -induced changes in chirp structure and simultaneously examined whether @entity3 alter the sexually dimorphic pattern of @entity2 -ir in a brain region (prepacemaker nucleus, PPn) known to control chirping. Our results demonstrate that, in females, @entity3 cause both the induction of chirping and an alteration of chirp structure; chirps recorded from @entity1 -implanted females had longer durations and more dramatic frequency and amplitude modulations compared to controls, and appear similar to those reported to be produced during spawning. Moreover, @entity1 -induced changes in chirping are correlated with increased expression of @entity2 -ir within specific brain nuclei of females. These changes may underly behavioral changes in chirping, since treated females showed a male-like pattern of @entity2 -ir in the PPn. However, alterations in @entity2 -ir were not restricted to the PPn, but also occurred in diencephalic regions related to pituitary function and reproductive behavior. The results suggest that @entity3 modulate chirping activity and cause both specific and wide-spread changes in @entity2 -ir that may relate to a functional system that interrelates pituitary function, reproductive behavior, and chirping.

title: XXXX -induced changes in electrocommunicatory behavior are correlated with changes in substance P-like immunoreactivity in the brain of the electric fish Apteronotus leptorhynchus.

answer: @entity1


abstract: The @entity1 locus coeruleus contains a population of noradrenergic neurons which express the neurotrophin receptor p75 (von Bartheld and Bothwell, 1992). To determine which neurotrophin may regulate the development of noradrenergic neurons in the @entity1 locus coeruleus, expression of trk receptors, retrograde transport of neurotrophins, and responses to NGF were examined. P75-expressing noradrenergic neurons were found to project to the basal forebrain. They transport radio-iodinated NGF after injections into this target. The retrograde transport of NGF is specific to the noradrenergic neuronal population as evidenced by double labeling with antibodies against @entity0 -beta-hydroxylase. The same neuronal population expresses @entity3 receptor mRNA. The size of noradrenergic neurons in the locus coeruleus proper, but not in the nucleus subcoeruleus, is significantly increased after injections of NGF into the telencephalon, consistent with the hypothesis that target-derived NGF provides trophic support. Noradrenergic coeruleus neurons are rescued from toxic effects of @entity2 injected into the telencephalon when NGF is injected into the midbrain. NGF has no rescue effect when it is coinjected with @entity2 into the telencephalon. In explant or dissociated cultures, noradrenergic coeruleus neurons do not respond to elevated levels of NGF with increased neurite outgrowth. Taken together, these results suggest that NGF plays a role in the development and maintenance of noradrenergic coeruleus neurons in the @entity1 brain. The data also support our previous conclusion that major species differences exist between birds ( @entity1 ) and mammals with regard to trophic regulation of presumptive homologous neuronal populations.

title: Noradrenergic neurons in the locus coeruleus of birds express XXXX , transport NGF, and respond to NGF.

answer: @entity3


abstract: BACKGROUND: Guidelines for the prevention of @entity3 call for low-density lipoprotein @entity2 ( @entity8 ) reduction as the primary target of treatment and reduction of @entity4 (TG) as an additional target. OBJECTIVE: The purpose of this study was to investigate the ability of @entity6 and @entity7 to reduce @entity8 and TG concentrations and to meet 3 target lipid levels: @entity8 <or=2.6 mmol/L; TG <or=1.5 mmol/L; and both @entity8 <or=2.6 mmol/L and TG <or=1.5 mmol/L. METHODS: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult @entity0 aged 35 to 75 years with @entity1 and @entity5 , defined as @entity8 concentration >or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg @entity6 or 20 mg @entity7 . Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National @entity2 Education Program level of @entity8 (<or=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. RESULTS: The intent-to-treat analysis included 552 @entity0 (418 @entity0 , 134 @entity0 ) randomized to receive @entity6 and 535 (404 @entity0 , 131 @entity0 ) randomized to receive @entity7 . The number of @entity0 enrolled in the study allowed the evaluation fo the drugs' effects on TG. @entity0 demogrpahic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with @entity7 , @entity6 produced significantly greater reductions in @entity8 (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with @entity7 -treated @entity0 , a significantly greater number of @entity6 -treated @entity0 reached the @entity8 target after 8 weeks (45% vs 24%; P < 0.001). Fewer @entity6 @entity0 needed to have their dose doubled; nevertheless more @entity6 @entity0 reached the @entity8 target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 @entity0 (2.2%) in the @entity6 group and in 13 @entity0 (2.4%) in the @entity7 group. CONCLUSIONS: @entity6 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than @entity7 20 or 40 mg/d in reducing @entity8 and TG levels and at achieving recommended lipid targets in this selected @entity0 population with @entity1 and @entity5 . Both statis were well tolerated.

title: A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of @entity6 and @entity7 in reaching low-density lipoprotein XXXX and triglyceride targets: the treat-to-target (3T) study.

answer: @entity2


abstract: BACKGROUND: Guidelines for the prevention of @entity3 call for low-density lipoprotein @entity2 ( @entity8 ) reduction as the primary target of treatment and reduction of @entity4 (TG) as an additional target. OBJECTIVE: The purpose of this study was to investigate the ability of @entity6 and @entity7 to reduce @entity8 and TG concentrations and to meet 3 target lipid levels: @entity8 <or=2.6 mmol/L; TG <or=1.5 mmol/L; and both @entity8 <or=2.6 mmol/L and TG <or=1.5 mmol/L. METHODS: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult @entity0 aged 35 to 75 years with @entity1 and @entity5 , defined as @entity8 concentration >or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg @entity6 or 20 mg @entity7 . Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National @entity2 Education Program level of @entity8 (<or=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. RESULTS: The intent-to-treat analysis included 552 @entity0 (418 @entity0 , 134 @entity0 ) randomized to receive @entity6 and 535 (404 @entity0 , 131 @entity0 ) randomized to receive @entity7 . The number of @entity0 enrolled in the study allowed the evaluation fo the drugs' effects on TG. @entity0 demogrpahic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with @entity7 , @entity6 produced significantly greater reductions in @entity8 (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with @entity7 -treated @entity0 , a significantly greater number of @entity6 -treated @entity0 reached the @entity8 target after 8 weeks (45% vs 24%; P < 0.001). Fewer @entity6 @entity0 needed to have their dose doubled; nevertheless more @entity6 @entity0 reached the @entity8 target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 @entity0 (2.2%) in the @entity6 group and in 13 @entity0 (2.4%) in the @entity7 group. CONCLUSIONS: @entity6 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than @entity7 20 or 40 mg/d in reducing @entity8 and TG levels and at achieving recommended lipid targets in this selected @entity0 population with @entity1 and @entity5 . Both statis were well tolerated.

title: A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of @entity6 and XXXX in reaching low-density lipoprotein @entity2 and triglyceride targets: the treat-to-target (3T) study.

answer: @entity7


abstract: BACKGROUND: Guidelines for the prevention of @entity3 call for low-density lipoprotein @entity2 ( @entity8 ) reduction as the primary target of treatment and reduction of @entity4 (TG) as an additional target. OBJECTIVE: The purpose of this study was to investigate the ability of @entity6 and @entity7 to reduce @entity8 and TG concentrations and to meet 3 target lipid levels: @entity8 <or=2.6 mmol/L; TG <or=1.5 mmol/L; and both @entity8 <or=2.6 mmol/L and TG <or=1.5 mmol/L. METHODS: The Treat-to-Target (3T) Study was a 52-week, multicenter, randomized, parallel-group study. Using the double-blind, double-dummy technique, adult @entity0 aged 35 to 75 years with @entity1 and @entity5 , defined as @entity8 concentration >or=4.0 mmol/L (>or=155 mg/dL), were randomized in a 1:1 ratio to receive once-daily oral treatment with 20 mg @entity6 or 20 mg @entity7 . Fasting (12-hour) blood samples for the estimation of lipid levels and clinical laboratory values were collected after 4, 8, 12, 26, and 52 weeks. The dose was doubled after 12 weeks if the target National @entity2 Education Program level of @entity8 (<or=2.6 mmol/L [100 mg/dL]) was not reached at 8 weeks. RESULTS: The intent-to-treat analysis included 552 @entity0 (418 @entity0 , 134 @entity0 ) randomized to receive @entity6 and 535 (404 @entity0 , 131 @entity0 ) randomized to receive @entity7 . The number of @entity0 enrolled in the study allowed the evaluation fo the drugs' effects on TG. @entity0 demogrpahic characteristics were similar for the 2 treatment groups, and there were no differences in baseline lipid values. Compared with @entity7 , @entity6 produced significantly greater reductions in @entity8 (8 weeks: -46% vs -40%, P < 0.001; 52 weeks: -49% vs -44%, P < 0.001) and in TG (8 weeks: -23% vs -14%, P < 0.001; 52 weeks: -24% vs -16%, P < 0.001). Compared with @entity7 -treated @entity0 , a significantly greater number of @entity6 -treated @entity0 reached the @entity8 target after 8 weeks (45% vs 24%; P < 0.001). Fewer @entity6 @entity0 needed to have their dose doubled; nevertheless more @entity6 @entity0 reached the @entity8 target after 52 weeks (61% vs 41%; P < 0.001). Both statins were well tolerated. Muscular symptoms occurred in 12 @entity0 (2.2%) in the @entity6 group and in 13 @entity0 (2.4%) in the @entity7 group. CONCLUSIONS: @entity6 20 or 40 mg/d for up to 1 year of treatment was significantly more effective than @entity7 20 or 40 mg/d in reducing @entity8 and TG levels and at achieving recommended lipid targets in this selected @entity0 population with @entity1 and @entity5 . Both statis were well tolerated.

title: A 52-week, multicenter, randomized, parallel-group, double-blind, double-dummy study to assess the efficacy of XXXX and @entity7 in reaching low-density lipoprotein @entity2 and triglyceride targets: the treat-to-target (3T) study.

answer: @entity6


abstract: @entity3 ( @entity3 ) @entity2 ( @entity1 ) nick end labeling (TUNEL) is the method of using the @entity3 enzyme to covalently attach a tagged form of @entity1 to 3' ends of double- and single-stranded DNA breaks in cells. It is a reliable and useful method to detect DNA damage and cell death in situ. This video describes dissection, tissue processing, sectioning, and fluorescence-based TUNEL labeling of @entity0 skeletal muscle. It also describes a method of semi-automated TUNEL signal quantitation. Inherent normal tissue features and tissue processing conditions affect the ability of the @entity3 enzyme to efficiently label DNA. Tissue processing may also add undesirable autofluorescence that will interfere with TUNEL signal detection. Therefore, it is important to empirically determine tissue processing and TUNEL labeling methods that will yield the optimal signal-to-noise ratio for subsequent quantitation. The fluorescence-based assay described here provides a way to exclude autofluorescent signal by digital channel subtraction. The TUNEL assay, used with appropriate tissue processing techniques and controls, is a relatively fast, reproducible, quantitative method for detecting apoptosis in tissue. It can be used to confirm DNA damage and apoptosis as pathological mechanisms, to identify affected cell types, and to assess the efficacy of therapeutic treatments in vivo.

title: Detection and Analysis of DNA Damage in XXXX Skeletal Muscle In Situ Using the TUNEL Method.

answer: @entity0


abstract: BACKGROUND:: The pipeline @entity4 device (PED) has been used for treatment of @entity2 . Little is known about the use of the PED in @entity5 . OBJECTIVE:: To assess the safety and efficacy of the PED in @entity5 . METHODS:: This is a case series with prospective data collection on 20 @entity0 with freshly @entity5 who were treated with PED (with or without adjunctive coiling) at 2 cerebrovascular centers. @entity0 were loaded with aspirin and clopidogrel or received an infusion of tirofiban intraoperatively. RESULTS:: Hunt and Hess grades were I in 7 @entity0 (35%), II in 9 (45%), and III in 4 (20%). The mean duration from @entity3 to PED placement was 7    7.0 days. A single device was used in all but 1 @entity0 (95%). The procedure was staged in 20%. There was only 1 complication (5%); this was a fatal intraoperative aneurysm dome @entity1 that occurred during adjunctive coil deployment. Adjunctive coiling was used in 30%. No @entity0 required an invasive procedure after PED placement. Follow-up angiography (mean, 5.3    4.2 months; range, 2-12 months) showed 100% occlusion in 12 (80%) and incomplete occlusion in 3 @entity0 (20%). At latest follow-up, 19 @entity0 achieved a favorable outcome (modified rankin scale 0-2). CONCLUSION:: In our preliminary experience, treatment of @entity5 with the PED was associated with low complication rates, high occlusion rates, and favorable outcomes. These findings suggest that PED may be a safe and effective option for @entity0 with favorable Hunt and Hess grades and @entity2 to treat with conventional methods. ABBREVIATIONS:: FDA, Food and Drug AdministrationPED, pipeline @entity4 device.

title: Treatment of XXXX With the Pipeline Embolization Device.

answer: @entity5


abstract: BACKGROUND:: The use of flow diverters such as the pipeline embolization device (PED) for treatment of @entity3 carries the risk of side @entity5 . OBJECTIVE:: To determine the incidence and clinical outcomes associated with supraclinoid internal carotid artery (ICA) @entity5 after deployment of PEDs for ICA @entity4 . METHODS:: We reviewed @entity0 who underwent endovascular treatment with PEDs for ICA @entity4 between June 2011 and March 2013. Forty-nine @entity0 (43 @entity0 , mean age 56.3    1.8 years, 68 @entity4 ) in whom PEDs traversed the origin of supraclinoid ICA branches (ophthalmic [OA], posterior communicating [PcommA], and anterior choroidal artery [AChA]) were selected for this study. Follow-up angiograms (mean follow-up, 12.8    0.8 months) were studied to determine the location of PEDs and the patency of ICA branches. RESULTS:: PEDs were placed across the ostia of 49 @entity6 , 14 PcommAs, and 11 AChAs. Multiple PEDs were deployed in 16 @entity0 . Rate of @entity5 was 4% (2/49) for the OA, 7.1% (1/14) for the PcommA, and 0% for the AChA. @entity0 with @entity5 did not endure new @entity1 . ICA @entity5 was not associated with the number of PEDs covering the ostia (P = .76) or the origin of ICA branches from the @entity4 (P = .24). CONCLUSION:: The incidence of major @entity2 after treatment with PEDs was low. These events were not associated with new @entity1 nor were they related to the number of PEDs deployed or the origin of ICA branches from the @entity4 . ABBREVIATIONS:: AChA, anterior choroidal arteryICA, internal carotid arteryOA, ophthalmic arteryPED, pipeline embolization devicePcommA, posterior communicating artery.

title: Incidence and Clinical Implications of Carotid Branch Occlusion Following Treatment of Internal Carotid XXXX With the Pipeline Embolization Device.

answer: @entity3


abstract: There is an expanding role for interleukin (IL)-1 in diseases from @entity1 . More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of the IL-1 family of receptors contains a domain, which is highly homologous to the cytoplasmic domains of all toll-like receptors (TLRs). This domain, termed "toll IL-1 receptor (TIR) domain," signals as does the IL-1 receptors; therefore, inflammation due to the TLR and the IL-1 families is nearly the same. Fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of a broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. @entity4 is the most studied member of the IL-1 family because of its role in mediating @entity5 . However, a role for @entity2 in disease is being validated because of the availability of a neutralizing monoclonal antibody to @entity0 @entity2 . There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring @entity3 , which binds to the IL-1 receptor and prevents the binding of @entity4 as well as @entity2 . Rilonacept is a soluble decoy receptor that neutralizes primarily @entity4 but also @entity2 . Canakinumab is a human monoclonal antibody that neutralizes only @entity4 . Thus, a causal or significant contributing role can be established for @entity4 and @entity2 in @entity0 disease.

title: An expanding role for @entity2 blockade from XXXX .

answer: @entity1


abstract: There is an expanding role for interleukin (IL)-1 in diseases from @entity1 . More than any other cytokine family, the IL-1 family is closely linked to innate inflammatory and immune responses. This linkage is because the cytoplasmic segment of all members of the IL-1 family of receptors contains a domain, which is highly homologous to the cytoplasmic domains of all toll-like receptors (TLRs). This domain, termed "toll IL-1 receptor (TIR) domain," signals as does the IL-1 receptors; therefore, inflammation due to the TLR and the IL-1 families is nearly the same. Fundamental responses such as the induction of cyclo-oxygenase type 2, increased surface expression of cellular adhesion molecules and increased gene expression of a broad number of inflammatory molecules characterizes IL-1 signal transduction as it does for TLR agonists. @entity4 is the most studied member of the IL-1 family because of its role in mediating @entity5 . However, a role for @entity2 in disease is being validated because of the availability of a neutralizing monoclonal antibody to @entity0 @entity2 . There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring @entity3 , which binds to the IL-1 receptor and prevents the binding of @entity4 as well as @entity2 . Rilonacept is a soluble decoy receptor that neutralizes primarily @entity4 but also @entity2 . Canakinumab is a human monoclonal antibody that neutralizes only @entity4 . Thus, a causal or significant contributing role can be established for @entity4 and @entity2 in @entity0 disease.

title: An expanding role for XXXX blockade from @entity1 .

answer: @entity2


abstract: Wound healing is typically divided into 4 stages; disruption of any one of these stages can impair this process. This integrative review summarizes findings from key studies suggesting that @entity3 may exert a clinically relevant impact on wound healing. For example, stress has been shown to decrease levels of inflammatory mediators, prolonging the inflammatory stage of healing, and increasing overall healing time. @entity2 has also been linked with impeding wound healing. Hostility has also been correlated with decreased inflammatory mediators, conversely, effective communication has shown faster healing time. Compounding factors such as unhealthy behaviors are also linked to poor wound healing, such as decreased sleep, poor nutrition, reduced exercise, and increased @entity1 use. Clinical evidence suggests that @entity1 exposure can reduce angiogenesis. Limited sleep decreases @entity5 secretion, resulting in decreased monocyte migration and activation of macrophages. @entity4 can decrease capillary formation, collagen synthesis, and wound remodeling. Such evidence challenges clinicians to consider psychological factors when treating wound care @entity0 .

title: XXXX and its impact on wound healing: an integrative review.

answer: @entity3


abstract: The most common adult primary @entity5 , @entity3 ( @entity3 ), is characterized by fifteen months median @entity0 survival and has no clear etiology. We and others have identified the presence of @entity7 ) gene products endogenously expressed in @entity3 tissue and primary cells, with a subset of viral genes being consistently expressed in most samples. Among these viral genes, several have important oncomodulatory properties, regulating @entity1 stemness, proliferation, immune evasion, invasion and angiogenesis. These findings lead us to hypothesize that a specific HCMV gene signature may be associated with @entity3 pathogenesis. To investigate this hypothesis, we used @entity2 cell lines and @entity2 stem-like cells (GSC) infected with clinical and laboratory HCMV strains and measured relative viral gene expression levels along several time points up to 15 weeks post-infection. While HCMV gene expression was detected in several infected @entity2 lines through week 5 post-infection, only HCMV-infected GSC expressed viral gene products 15 weeks post-infection. Efficiency of infection across time was higher in GSC compared to cell lines. Importantly, HCMV-infected GSC outlived their uninfected counterparts, and this extended survival was paralleled by increased tumorsphere frequency and upregulation of stemness regulators, such as @entity8 , p- @entity6 , and @entity9 (a novel HCMV target identified in this study). @entity4 ( @entity4 ) treatment significantly upregulated HCMV gene expression in long-term infected @entity2 , suggesting that pro-inflammatory signaling in the @entity1 milieu may further augment HCMV gene expression and subsequent @entity1 progression driven by viral-induced cellular signaling. Together, our data support a critical role for long-term, low-level HCMV infection in promoting survival, stemness, and proliferation of GSC that could significantly contribute to @entity3 pathogenesis.

title: @entity7 gene expression in long-term infected XXXX stem cells.

answer: @entity2