abstract: Subcutaneous @entity4 (SCPTCL) is characterized by primary involvement of the subcutaneous fat in a manner mimicking @entity7 . We studied 16 cases of this @entity3 to define its immunophenotypical profile as well as cellular origin. Involvement of the subcutaneous fat in a lacelike pattern with neoplastic cells rimming individual fat spaces was present in all cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were @entity2 +, whereas three were negative for both @entity1 and @entity2 . Twelve cases were stained for betaF1; of these, eight were betaF1+ and four were betaF1-. Focal staining for @entity6 and @entity8 was seen in 2 of 13 and two of eight cases, respectively. Intense diffuse positivity for the cytotoxic granular proteins @entity9 ( @entity9 ) and perforin was present in all cases, indicating an origin from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma gene rearrangement by polymerase chain reaction. Controls included seven cases of benign @entity7 and seven other peripheral T cell lymphomas involving the skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise specified (PTL,NOS), four @entity5 ( @entity5 ), one T/NK cell @entity3 . The seven cases of @entity7 lacked cytological atypia and were characterized by an admixture of @entity1 + and @entity2 + cells with interspersed aggregates of L26+ B cells. Only infrequent cells showed staining for @entity9 and perforin. In the control cases of @entity4 , the infiltrate had a tendency for dermal and sometimes even epidermal involvement, with sheeting out of malignant cells, in contrast to the characteristic subcutaneous localization and rimming of fat spaces noted in SCPTCL. The two PTL, NOS were @entity1 + and negative for both @entity9 and perforin. Although the remaining controls expressed @entity9 and perforin, in keeping with their cytotoxic T or natural killer (NK) cell origin, histological and other immunophenotypical features allowed distinction from SCPTCL. Five cases of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit. All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the mechanism of cell death in these @entity0 . Our study indicates that SCPTCL constitutes a distinctive clinicopathological entity derived from cytotoxic T lymphocytes and should be differentiated from other benign and malignant lymphoid infiltrates involving the subcutis. The apoptosis seen in these @entity0 may be mediated by release of cytotoxic granular proteins.

title: Subcutaneous XXXX is a @entity0 of cytotoxic T lymphocytes.

answer: @entity4


abstract: BACKGROUND: The extraction of RNA from leukocytes for reverse transcription-PCR (RT-PCR) is time-consuming and contributes to variation in analysis of the Philadelphia (Ph1) chromosome of @entity1 ( @entity1 ) by RT-PCR. To detect residual @entity1 after bone marrow transplantation, mRNA from at least 10(5) leukocytes should be analyzed, but the RNase activity of the cells precludes simple leukocytes lysis as an alternative to RNA extraction. We sought to identify the main source of RNase activity of leukocytes. METHODS: We used a three-step chromatographic process and @entity0 sequence analysis. We selected eosinophil-free granulocytes by using a biotinylated @entity2 antibody and selected mononuclear cells by fractionating the leukocytes with a Ficoll-Paque(R) density gradient. RESULTS: Chromatography and @entity0 sequencing identified @entity3 ( @entity3 ) as the main source of leukocyte RNase. Depletion of eosinophils reduced the @entity3 content of cell lysates by approximately 90%, allowing a signal from a lysate of 50 K562 Ph1-positive cells mixed with 10(5) @entity2 (+) granulocytes that was equivalent to 77% of the signal in the absence of leukocytes. A similar lysate with mononuclear cells gave a signal equivalent to 53% of that without mononuclear cells. RNA extraction gave a signal equivalent to only 24% of the leukocyte-free control. CONCLUSION: The depletion of eosinophils during the preparation of leukocyte samples for RT-PCR efficiently reduces the risk of mRNA degradation by ribonucleases, enabling RT-PCR analysis directly from cell lysates with a better signal than can be obtained by RNA extraction.

title: Major interference from leukocytes in reverse transcription-PCR identified as neurotoxin ribonuclease from eosinophils: detection of residual XXXX from cell lysates by use of an eosinophil-depleted cell preparation.

answer: @entity1


abstract: Many studies seek to explore the impact of extrinsic soluble factors present in serum, interstitial fluids or cell-conditioned media on cells in vitro. A convenient approach to elucidate the effects of a particular factor is its selective neutralization. However, intrinsic production of soluble factors such as cytokines by the cultured cells is common and can have an impact via autocrine mechanisms. The addition of cytokine-specific neutralizing antibodies leads to neutralization of the targeted factors irrespective of their source and affects paracrine and autocrine effects alike. Thus, neutralization assays are not suitable to irrevocably demonstrate that the examined factors exert their effect via a paracrine mechanism. We were interested in investigating the impact of immunosuppressive factors present in @entity0 -associated @entity2 by dissecting paracrine versus autocrine effects of @entity1 ( @entity1 ) and @entity3 ( @entity3 ) on the activation of monocyte-derived dendritic cells (DC). We explored several methods of depletion based on introduction of the neutralizing antibodies bound to beads. Here we describe the pitfalls of the investigated depletion approaches and show the importance of monitoring the presence of residual neutralizing antibodies in the sample upon depletion, which impacts on the suitability of the approach to distinguish paracrine from autocrine effects. Only one of three investigated approaches showed no dislocation of neutralizing antibody from the beads into the sample. This method, which is based on covalently linking antibody to magnetic beads harbouring a reactive group allowed for the complete removal of the investigated factors from @entity2 and represents an elegant tool to elucidate immunoregulatory or -stimulatory cytokine networks in considerably more depth than the use of neutralizing antibodies in cell cultures alone can contribute.

title: Antibody-mediated depletion of immunosuppressive factors from @entity0 -associated XXXX for investigation of paracrine versus autocrine effects.

answer: @entity2


abstract: Mitochondrial membrane potential (delta psi(m)) was determined in intact isolated nerve terminals using the membrane potential-sensitive probe JC-1. Oxidative stress induced by @entity2 (0.1-1 mM) caused only a minor decrease in delta psi(m). When complex I of the respiratory chain was inhibited by @entity8 (2 microM), delta psi(m) was unaltered, but on subsequent addition of @entity2 , delta psi(m) started to decrease and collapsed during incubation with 0.5 mM @entity2 for 12 min. The @entity4 level and [ @entity4 ]/[ @entity5 ] ratio were greatly reduced in the simultaneous presence of @entity8 and @entity2 . @entity2 also induced a marked reduction in delta psi(m) when added after @entity9 (10 microM), an inhibitor of @entity10 . @entity2 (0.1 or 0.5 mM) inhibited @entity11 dehydrogenase and decreased the steady-state @entity6 level in nerve terminals. It is concluded that there are at least two factors that determine delta psi(m) in the presence of @entity2 : (a) The @entity7 level reduced owing to inhibition of @entity11 dehydrogenase is insufficient to ensure an optimal rate of respiration, which is reflected in a fall of delta psi(m) when the @entity10 is not functional. (b) The greatly reduced @entity4 level in the presence of @entity8 and @entity2 prevents maintenance of delta psi(m) by @entity10 . The results indicate that to maintain delta psi(m) in the nerve terminal during @entity2 -induced oxidative stress, both complex I and @entity10 must be functional. Collapse of delta psi(m) could be a critical event in @entity3 in @entity0 or @entity1 when @entity2 is generated in excess and complex I of the respiratory chain is simultaneously impaired.

title: Depolarization of in situ mitochondria due to hydrogen peroxide-induced oxidative stress in nerve terminals: inhibition of XXXX dehydrogenase.

answer: @entity11


abstract: A fusion protein of @entity0 liver @entity3 with @entity2 -cytochrome P450 reductase was expressed genetically in @entity1 microsomal membranes. This flavo-cytochrome is active in 6-hydroxylation of @entity4 . Rotational diffusion of the fusion protein was examined by observing the flash-induced absorption anisotropy r(t) of the P450.CO complex. Theoretical analysis of r(t) was performed based on a "rotation-about-membrane normal" model. The absorption anisotropy decayed within 2 ms to a time-independent value r(3). Forty percent of the fusion protein rotated with a rotational relaxation time phi of 1.35 ms. Treatment with high salt increased the mobile population of the fusion protein to 62% with phi = 0.96 ms. The mobile population of the fusion protein is close to that of @entity3 coexpressed with the P450 reductase and greater than that of @entity3 alone [Iwase et al. (1991) Biochemistry 30, 8347-8351]. The large mobile population of the fusion protein provides evidence that @entity3 is mobilized by forming associations with P450 reductase in microsomal membranes.

title: Dynamic mobility of genetically expressed fusion protein between cytochrome P4501A1 and @entity2 -cytochrome P450 reductase in XXXX microsomes.

answer: @entity1


abstract: Ultrahigh molecular weight @entity2 (UHMWPE) is widely used as bone-replacement material for articulating surfaces due to its excellent wear resistance and low coefficient of friction. But, the @entity3 , generated during abrasion between mating surfaces, leads to aseptic loosening of implants. Thus, various reinforcing agents are generally utilized, which may alter the surface and biological properties of UHMWPE. In the current work, the cellular response of compression molded UHMWPE upon reinforcement of bioactive multiwalled @entity1 nanotubes (MWCNTs) and bioinert @entity4 ( @entity5 ) is investigated. The phase retention and stability were observed using X-ray diffraction, Raman spectroscopy and Fourier transform infrared (FTIR) spectroscopy. The reinforcement of MWCNTs and @entity5 has shown to alter the wettability (from contact angle of ~88    2   to ~118    4  ) and surface energy (from ~23.20 to ~17.75 mN/m) of composites with respect to UHMWPE, without eliciting any adverse effect on cytocompatibility for the L929 @entity0 fibroblast cell line. Interestingly, the cellular growth of the L929 @entity0 fibroblast cell line is observed to be dominated by the dispersion fraction of surface free energy (SFE). After 48 h of incubation period, a decrease in metabolic activity of MWCNT- @entity5 reinforced composites is attributed to apatite formation that reduces the dispersion fraction of surface energy. The mineralized apatite during incubation was confirmed and quantified by energy dispersive spectroscopy and X-ray diffraction respectively. Thus, the dispersion fraction of surface free energy can be engineered to play an important role in achieving enhanced metabolic activity of the MWCNT- @entity5 reinforced UHMWPE biopolymer composites.

title: Dispersion fraction enhances cellular growth of XXXX nanotube and @entity4 reinforced ultrahigh molecular weight @entity2 biocomposites.

answer: @entity1


abstract: BACKGROUND AND PURPOSE: Amyotrophic @entity5 is a progressive @entity5 that involves @entity3 upper and lower motor neurons. In @entity0 with @entity4 , pathologic studies and ex vivo high-resolution MR imaging at ultra-high field strength revealed the co-localization of @entity1 and activated microglia distributed in the deep layers of the primary motor cortex. The aims of the study were to measure the cortical thickness and evaluate the distribution of @entity1 -related signal changes in the primary motor cortex of @entity0 with @entity4 as possible in vivo biomarkers of @entity5 . MATERIALS AND METHODS: Twenty-two @entity0 with definite @entity4 and 14 healthy subjects underwent a high-resolution 2D multiecho gradient-recalled sequence targeted on the primary motor cortex by using a 7T scanner. Image analysis consisted of the visual evaluation and quantitative measurement of signal intensity and cortical thickness of the primary motor cortex in @entity0 and controls. Qualitative and quantitative MR imaging parameters were correlated with electrophysiologic and laboratory data and with clinical scores. RESULTS: Ultra-high field MR imaging revealed @entity2 in the deep layers of the primary motor cortex of @entity0 with @entity4 with a diagnostic accuracy of 71%. Signal hypointensity of the deep layers of the primary motor cortex correlated with @entity5 (r = -0.47; P < .001) and with disease progression rate (r = -0.60; P = .009). CONCLUSIONS: The combined high spatial resolution and sensitivity to paramagnetic substances of 7T MR imaging demonstrate in vivo signal changes of the cerebral motor cortex that resemble the distribution of activated microglia within the cortex of @entity0 with @entity4 . Cortical thinning and signal hypointensity of the deep layers of the primary motor cortex could constitute a marker of @entity5 in @entity0 with @entity4 .

title: High-Resolution 7T MR Imaging of the Motor Cortex in XXXX .

answer: @entity4


abstract: @entity2 (AP) is an endogenous neurosteroid. It modulates the effect of y-amino-butyric acid ( @entity1 ) on the @entity1 type A (GABAA) receptor, which leads to increased receptor activity. Since the @entity1 -system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABAA receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 @entity0 were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.

title: Isoallopregnanolone antagonize @entity2 -induced effects on saccadic eye velocity and self-reported sedation in XXXX .

answer: @entity0


abstract: UNASSIGNED: The aim of this study was to investigate the effect of @entity2 (Hp) on cyclooxygenase-2 (COX-2) and inducible @entity1 synthase ( @entity4 ) levels in @entity0 with @entity3 and its clinical significance. A total of 114 @entity0 with @entity3 , 57 whom were positive for Hp (observation group) and 57 of whom were negative for Hp (control group), were selected for the study. The mRNA levels of COX-2 and @entity4 in the gastric @entity3 tissue from the two groups of @entity0 were analyzed through the reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression levels of COX-2 and @entity4 were analyzed using western blotting and an @entity4 kit, respectively. In addition, normal @entity0 gastric mucosal GES-1 cells were cultured in vitro and stimulated by Hp for 3, 6, 9 and 12 h. The variations in the mRNA and protein levels of COX-2 and @entity4 were then analyzed via RT-qPCR and western blotting. Compared with the control group, the mRNA levels of COX-2 and @entity4 in the gastric tissue from the observation group were significantly increased (P<0.05). Furthermore, the expression level of COX-2 and @entity4 protein in the gastric tissue from the observation group was significantly higher than that in the tissue from the control group (P<0.05). In vitro analysis showed that the COX-2 and @entity4 mRNA and protein levels were significantly increased in the Hp-stimulated normal @entity0 gastric mucosal GES-1 cells compared with those in the unstimulated cells. Furthermore, the effect was time-dependent (P<0.05). In conclusion, COX-2 and @entity4 are the main inflammatory markers. Hp can induce high expression levels of COX-2 and @entity4 in gastric @entity3 tissue, which may be associated with the occurrence and development of @entity3 .

title: Effect of @entity2 on cyclooxygenase-2 and inducible @entity1 synthase in @entity0 with XXXX and its clinical significance.

answer: @entity3


abstract: OBJECTIVE: Obesity and overweight are increasing conditions. Adipose tissue with proinflammatory properties could be involved in @entity4 ( @entity4 ) activity and radiographic progression. This study aims to investigate the influence of overweight and @entity2 on @entity4 activity and severity. METHODS: We conducted a systematic review and metaanalysis to assess the association of body mass index (BMI) categories with the Disease Activity Score in 28 joints (DAS28), functional disability [Health Assessment Questionnaire (HAQ)], and @entity1 in @entity0 with @entity4 . We searched Medline through PubMed, EMBASE, and the Cochrane Database of Systematic Reviews for all studies assessing DAS28, HAQ, or/and radiographic damage according to predefined BMI groups. RESULTS: Among the 737 citations retrieved, 58 articles met the inclusion criteria and 7 were included in the metaanalysis. DAS28 was higher in @entity2 (BMI > 30 kg/m(2)) than @entity2 (BMI  <= 30 kg/m(2)) @entity0 (mean difference 0.14, 95% CI 0.01-0.27, p = 0.04, I(2) = 0%). HAQ score was also higher among @entity2 @entity0 (mean difference 0.10, 95% CI 0.01-0.19, p = 0.03, I(2) = 0%). @entity1 was negatively associated with @entity2 (standardized mean difference -0.15, 95% CI -0.29 to -0.02, p = 0.03, I(2) = 38%). CONCLUSION: Obesity in @entity4 is associated with increased DAS28 and HAQ score and with lower @entity1 . These associations mainly result from an increase of subjective components of the DAS28 (total joint count and global health assessment) in @entity2 @entity0 . Conflicting results were reported concerning @entity3 markers ( @entity5 and erythrocyte sedimentation rate).

title: Association of Body Mass Index Categories with Disease Activity and Radiographic Joint Damage in XXXX : A Systematic Review and Metaanalysis.

answer: @entity4


abstract: PURPOSE: To describe a case of @entity8 , presenting with @entity5 , @entity11 , @entity10 , and @entity4 after @entity13 . METHODS: The authors report a 7-year-old @entity0 with @entity2 in his left eye after embolization of a pineal @entity12 secondary to @entity8 . Ophthalmic evaluation, fundus photography, @entity6 angiography, spectral domain optical coherence tomography, electroretinogram, examination under anesthesia, and pars plana vitrectomy ( @entity9 ) were performed. RESULTS: Fundus examination of the left eye revealed extensive posterior segment @entity1 , vascular tortuosity, and @entity4 . Fluorescein angiography was remarkable for @entity3 , midperipheral nonperfusion, and associated leakage from multiple areas of @entity10 . Spectral domain optical coherence tomography was normal. Electroretinogram demonstrated decreased b-wave amplitude. The @entity0 was subsequently treated with 25-gauge pars plana vitrectomy, panretinal endophotocoagulation, and intravitreal bevacizumab. Five weeks after surgery, best-corrected visual acuity had improved to 20/40, and examination showed resolution of @entity4 and @entity10 . CONCLUSION: @entity7 , posterior segment @entity1 , and @entity4 suggested a combination of retinal involvement of @entity8 complicated by nontarget embolization.

title: @entity1 after @entity12 in a @entity0 with XXXX .

answer: @entity8


abstract: The promise of 'personalized @entity2 care' with therapies toward specific molecular aberrations has potential to improve outcomes. However, there is recognized heterogeneity within any given @entity2 -type from @entity0 to @entity0 (inter- @entity0 heterogeneity), and within an individual (intra- @entity0 heterogeneity) as demonstrated by molecular evolution through space ( @entity2 to @entity1 ) and time (after therapy). These issues have become hurdles to advancing @entity2 treatment outcomes with novel molecularly targeted agents. Classic trial design paradigms are challenged by heterogeneity, as they are unable to test targeted therapeutics against low frequency genomic 'oncogenic driver' aberrations with adequate power. Usual accrual difficulties to clinical trials are exacerbated by low frequencies of any given molecular driver. To address these challenges, there is need for innovative clinical trial designs and strategies implementing novel diagnostic biomarker technologies to account for inter- @entity0 molecular diversity and scarce tissue for analysis. Importantly, there is also need for pre-defined treatment priority algorithms given numerous aberrations commonly observed within any one individual sample. Access to multiple available therapeutic agents simultaneously is crucial. Finally intra- @entity0 heterogeneity through time may be addressed by serial biomarker assessment at the time of @entity2 progression. This report discusses various 'next-generation' biomarker-driven trial designs and their potentials and limitations to tackle these recognized molecular heterogeneity challenges. Regulatory hurdles, with respect to drug and companion diagnostic development and approval, are considered. Focus is on the 'Expansion Platform Design Types I and II', the latter demonstrated with a first example, 'PANGEA: Personalized Anti-Neoplastics for @entity3 '. Applying integral medium-throughput genomic and proteomic assays along with a practical biomarker assessment and treatment algorithm, 'PANGEA' attempts to address the problem of heterogeneity towards successful implementation of molecularly targeted therapies.

title: Next-generation clinical trials: Novel strategies to address the  challenge of XXXX molecular heterogeneity.

answer: @entity2


abstract: PURPOSE: The purpose of this investigation was to examine the effects of a modified version of a newly developed therapy for @entity2 and acquired @entity1 ( @entity1 ), Combined @entity2 and Apraxia of Speech Treatment (CAAST). METHOD: Four speakers with chronic @entity1 and @entity2 received CAAST in the context of multiple baseline designs. Dependent variables included language measures (i.e. production of correct information units (CIUs)) and speech production measures (i.e. speech intelligibility and percent correct consonants (PCC) in sentence repetition). RESULT: Three of the @entity0 demonstrated improved CIU production with treated picture sets and two also demonstrated generalization to untreated sets. All @entity0 achieved substantially increased CIU production in an untrained discourse context. Speech intelligibility increased for three of the @entity0 and increases in PCC were observed for all of the @entity0 at two weeks post-treatment. However, PCC improvements were maintained for only two of the speakers at six weeks post-treatment. CONCLUSION: The revised CAAST protocol was associated with improved changes in speech and generalization across contexts in comparison to the previous iteration of CAAST. However, focus on sentence production in generalization practice may have been detrimental to CIU production for one @entity0 .

title: Combined @entity2 and XXXX treatment (CAAST): Systematic replications in the development of a novel treatment.

answer: @entity1


abstract: Nineteen @entity0 with morphological abnormalities of the red blood cells are described, and these formed approximately 3% of the total cases of @entity1 . In two @entity0 the abnormal blood film developed after the insertion of an aortic and mitral valve prosthesis respectively, but in another two @entity0 the abnormal blood film was corrected by aortic valve surgery. Anisopoikilocytosis may have been associated with microangiopathic @entity2 in one @entity0 , but in the others the @entity1 was severe and other mechanical factors were not present. The mitral valve was involved in 16 @entity0 and the aortic valve in eight. Elliptocytosis was the only abnormality in 11 blood films, schistocytes and burr cells were present in seven, and in three there were a few microspherocytes. Family studies in seven @entity0 produced evidence of @entity4 in three. @entity2 was present in only two @entity0 . One of these had @entity3 , and the other developed overt @entity2 following the replacement of a diseased mitral valve by a Starr-Edwards prosthesis. In this latter case there was a transiently positive direct antiglobulin test, and the @entity2 and abnormal blood picture were corrected without further surgical treatment. @entity2 did not develop in 23 @entity0 after the insertion of an aortic valve prosthesis or homograft. Indirect evidence of haemolysis was obtained in some @entity0 who were not anaemic. There was a reticulocytosis in one third and serum haptoglobins were decreased or absent in over half of the @entity0 tested.

title: Red blood cell abnormalities in XXXX .

answer: @entity1


abstract: OBJECTIVES: To evaluate the impact of different dosages of @entity3 (TPM) add-on to stable antiepileptic therapy for refractory @entity1 in adults. MATERIAL AND METHODS: Pooled intention-to-treat analysis of six similarly designed double-blind, placebo-controlled trials, including 481 @entity0 treated with doses of TPM 200, 400, 600 and 800 mg/day, and 265 @entity0 receiving placebo. RESULTS: @entity2 were reduced by >/=50% from baseline in 41% of TPM-treated @entity0 and 15% of placebo-treated @entity0 (P < 0.001); 5 and 0.8%, respectively, were @entity2 -free (P < 0.003). TPM was significantly better than placebo regardless of gender, age, baseline @entity2 rate as well as number and type of concomitant antiepileptic drugs. Efficacy was statistically significant in favour of TPM at all dose levels: at least 50% @entity2 reduction was achieved in 40% of @entity0 with 200 mg, 41% with 400 mg, 44% with 600 mg and 41% with 800 mg TPM when compared with 15% with placebo (P </= 0.001 for each dosage arm vs placebo). The median reduction in monthly @entity2 frequency was 38%, 42%, 45% and 38% vs 8%, respectively (P </= 0.001). Moreover, response to TPM was significantly superior to placebo at each of the dose levels tested for most of the baseline variables. The total percentage of withdrawals increased with the dosage, and the withdrawals caused by adverse events increased from 3% with placebo to 7% with 200 mg TPM (not significant vs placebo), 15% with 400 mg TPM (P = 0.08), 16% with 600 mg TPM (P = 0.002) and 15% with 800 mg TPM (P = 0.003). CONCLUSION: The efficacy of TPM add-on in @entity1 is consistent across efficacy endpoints and independent of study population characteristics. The response at 200 mg TPM is similar to the response at higher doses, but as drop-outs caused by adverse events are more frequent above the 200 mg dose, this pooled analysis supports that 200 mg daily is a good target dose for add-on therapy in most @entity0 with @entity1 , showing an excellent balance between efficacy and tolerability.

title: A pooled analysis of adjunctive @entity3 in refractory XXXX .

answer: @entity1


abstract: @entity7 who are aware of their increased risk of developing @entity0 may suffer from high @entity3 . Chronic stress may interfere with NCA and low NCA is associated with increased @entity2 risk. We studied 80 @entity7 and 47 age- and education-matched healthy females (controls). Heparinized venous blood (30 ml) was drawn from all subjects between 8 and 9 A.M., and each @entity1 answered a set of psychologic questionnaires. In addition, the first-morning urine sample was collected. @entity7 scored significantly higher in @entity3 compared to controls. Levels of stress hormones in @entity7 were higher and in vitro secretion of @entity6 , IL-12 and @entity4 lower compared to controls. NCA against NK-resistant (MCF-7, COLO-205, U937) and NK-sensitive (K562) cell lines was significantly lower in @entity7 and much less augmented by in vitro preincubation with @entity6 or IL-12 compared to controls. NCA and in vitro @entity5 cytokine secretion were inversely correlated with the @entity3 and the level of stress hormones in blood or urine. High @entity3 and elevated levels of stress hormones are associated with impaired immune surveillance functions in @entity7 . This may contribute to the increased risk of @entity7 to develop @entity0 . An interventional trial to enhance coping and reduce stress levels may help to decrease the risk for @entity0 onset in @entity7 .

title: Increased @entity3 in daughters of XXXX @entity1 is associated with decreased natural cytotoxic activity, elevated levels of stress hormones and decreased secretion of @entity5 cytokines.

answer: @entity0


abstract: OBJECTIVE: To identify the most commonly used @entity0 -reported outcome (PRO) measures in clinical vestibular research, and to assess their test characteristics and applicability to the study of age-related @entity2 in clinical trials. DATA SOURCES: We performed a systematic review of the PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycINFO databases from 1950 to August 13,  2013. STUDY SELECTION: PRO measures were defined as outcomes that capture the subjective experience of the @entity0 (eg, symptoms, functional status, health perceptions, quality of life). Two independent reviewers selected studies that used PRO measures in clinical vestibular research. Disparities were resolved with consensus between the reviewers. Of 2260 articles initially found in the literature search, 255 full-text articles were retrieved for assessment. Of these, 104 met inclusion criteria for data collection. DATA EXTRACTION: PRO measures were identified by 2 independent reviewers. The 4 most commonly used PROs were evaluated for their applicability to the condition of age-related @entity2 . Specifically, for these 4 PROs, data were collected pertaining to instrument test-retest reliability, item domains, and target population of the instrument. DATA SYNTHESIS: A total of 50 PRO instruments were identified. The 4 most frequently used PROs were the Dizziness Handicap Inventory, Activities-specific Balance Confidence scale, Vertigo Symptom Scale-short form, and visual analog scale. Of these 4 PROs, 3 were validated for use in @entity0 with @entity3 and 1 was validated in community-dwelling older individuals with @entity1 . Items across the 4 PROs were categorized into 3 domains based on the International Classification of Functioning, Disability and Health: activity, participation, and body functions and structures. CONCLUSIONS: None of the most commonly used PRO instruments were validated for use in community-dwelling older adults with age-related @entity2 . Nevertheless, the 3 common domains of items identified across these 4 PRO instruments may be generalizable to older adults and provide a basis for developing a PRO instrument designed to evaluate the effectiveness of interventions targeted toward age-related @entity2 .

title: Systematic review of XXXX -reported outcome measures in clinical vestibular research.

answer: @entity0


abstract: Antimicrobial resistance among the Viridans group of streptococci (VGS) has emerged as a hindrance to effective antibiotic therapy. Our objective was to evaluate the prevalence of antibiotic-resistant VGS in healthy @entity0 . Plaque samples were collected from tooth and tongue surfaces of 102 healthy subjects. Serially diluted samples were inoculated onto BHI agar plates and Mitis Salivarius Agar (MSA) plates and incubated as appropriate. Representative colonies were identified to species level by standard methods. Susceptibility of the VGS was performed by determining the minimum inhibitory concentrations (MICs) of 11 antibiotics using Etest. Of the 540 VGS isolates from both sites, 58% were from the tooth surfaces and 42% from the tongue. The most prevalent were @entity12 (21.5%) and @entity4 (16.3%). Imipenem and @entity5 had excellent activities. Resistance rates to @entity3 , @entity2 , @entity8 , @entity7 , @entity6 and @entity10 , were 60.7, 40.8, 34.7, 32.6, 27.5 and 25.3%, respectively. Resistance rates to @entity1 and @entity9 were 15.9% and 15.4%, respectively. The majority of the @entity7 -resistant isolates were from the tongue; 41% versus 29%. At the species level, 26% and 23% of @entity12 and 23% and 14% of @entity11 from the tooth and tongue, respectively were resistant to @entity1 . The data show species-related and site-related variations in the susceptibility pattern and an emerging high prevalence of antibiotic-resistant VGS. The difference in the susceptibilities between the species underscores the importance of accurate-identification and the need for surveillance of antimicrobial resistance among clinical isolates in our hospitals.

title: High frequency of isolation of antibiotic-resistant oral Viridans streptococci from XXXX in Kuwait.

answer: @entity0


abstract: The metabolism of high grade @entity4 was studied in 15 @entity0 using intra-tumoural microdialysis. Two catheters were implanted during a stereotactic biopsy procedure: one in the @entity1 and one in the peri-tumoural tissue. The @entity0 were fully mobilized the same day as the operation. Microdialysis samples were collected the next day and subsequently analysed for @entity2 , @entity5 , @entity8 , @entity7 and @entity3 . The main objective was to establish base-line levels of the studied substances. In addition, an in vitro experiment was performed in order to estimate recovery for the flow rates and catheters used. @entity2 showed a tendency to be lower in @entity1 than in peri-tumoural tissue, indicating a high energy demand of the @entity1 . @entity5 was significantly higher in @entity1 tissue. This supports previous reports that high grade astrocytomas use glycolysis rather than respiration to meet their energy demand. The @entity1 were also classified into necrotic and non-necrotic, according to the radiological finding. The @entity1 showed significantly higher levels of @entity7 . They also presented a tendency to higher levels of @entity3 than the @entity1 . These findings might be explained by the release of intracellular @entity7 and of cell-membrane @entity3 by cell destruction. We believe that microdialysis in awake and mobilized @entity0 will prove to be a valuable tool in investigating metabolic events in malignant @entity6 especially during therapy.

title: Baseline levels of @entity2 metabolites, @entity7 and XXXX in malignant glioma assessed by stereotactic microdialysis.

answer: @entity3


abstract: OBJECTIVE: To evaluate exhaled @entity3 (e @entity3 ), exhaled CO (eCO), and serum @entity4 concentrations as diagnostic criteria for @entity0 @entity2 (BRD) and determine whether a combination of biomarkers would be useful for predicting health outcomes of heifer @entity0 . ANIMALS: 337 heifer @entity0 newly arrived at a feedlot. PROCEDURES: Body weights, serum @entity4 concentrations, and rumen temperatures were determined. @entity0 (n = 183) were randomly selected for breath sampling. Variables were compared among @entity0 that remained healthy and those requiring treatment. RESULTS: Body weight at the time of first and second antimicrobial treatments did not differ from that at arrival, whereas body weight at the time of third antimicrobial treatment was lower. Temperature was lower at arrival, compared with that during antimicrobial treatment. Ratio of e @entity3 :eCO(2) was lowest at arrival, intermediate at the first and second antimicrobial treatments, and greatest at the third antimicrobial treatment. Ratio of eCO:eCO(2) was greater at times of antimicrobial treatment, compared with arrival. Concentration of serum @entity4 was greatest at the time of the first antimicrobial treatment, lowest at the times of second and third treatments, and intermediate at arrival. Arrival ratios of e @entity3 : e @entity1 and eCO:eCO(2) and concentration of @entity4 did not differ among heifers subsequently treated 1, 2, or 3 times. CONCLUSIONS AND CLINICAL RELEVANCE: Although breath analysis was successfully implemented in a research feedlot, arrival rumen temperature, e @entity3 , eCO, and @entity4 concentration were not accurate in predicting occurrence of BRD during a preconditioning program. However, these biomarkers might support the diagnosis of BRD.

title: Evaluation of breath biomarkers and serum @entity4 concentration for diagnosis of @entity0 XXXX in heifers newly arrived at a feedlot.

answer: @entity2


abstract: OBJECTIVES: Previous studies have demonstrated that intranasal administration of inactivated (fixed) @entity4 (iFt) live vaccine strain (LVS) in conjunction with the mucosal adjuvant, cholera toxin B ( @entity7 ), provides full protection against subsequent lethal challenge with Ft LVS and partial protection against the more virulent Ft SchuS4 strain. Understanding the mechanisms of @entity7 -induced immune stimulation that confer protection against Ft will be valuable to the development of an effective vaccine against this highly virulent fatal pathogen. In this study, an in vitro system was utilized to further elucidate the immunologic adjuvant effect of @entity7 when administered with the fixed bacterial immunogen iFt. METHODS: The @entity1 macrophage cell line (RAW264.7) was treated with combinations of iFt and @entity7 . The treated RAW264.7 cells and their supernatants were collected and assessed for cell surface marker expression and cytokine secretion. In addition, the ability of RAW264.7 cells to present bacterial antigens (iFt or LVS) to an Ft-specific T-cell hybridoma cell line, following exposure to @entity7 , was analyzed. RESULTS: We found that RAW264.7 cells responded to treatment with iFt + @entity7 by an increased secretion of the proinflammatory cytokines interleukin 6 and @entity0 @entity2 factor a and upregulation of the surface expression of @entity3 and the costimulatory molecules @entity5 and @entity6 . Furthermore, the experimental vaccine treatment iFt + @entity7 enhanced the ability of macrophages to present iFt antigens to an FT-specific T-cell hybridoma cell line, although they failed to do so with LVS. CONCLUSION: The adjuvant @entity7 administered in conjunction with iFt showed evidence of enhancing an antigen-specific proinflammatory response in vitro. These observations allow us to define, in part, the mechanisms of immune activation conferred by mucosal administration of iFt + @entity7 against lethal @entity4 challenge.

title: Cholera toxin B induced activation of XXXX macrophages exposed to a fixed bacterial immunogen.

answer: @entity1


abstract: PURPOSE: To evaluate the impact of local superficial radiotherapy with respect to local control, survival, and @entity1 for @entity0 with "minimal" stage IA @entity3 ( @entity6 ). METHODS AND MATERIALS: Between 1954 and 1996 a total of 21 @entity0 were identified as receiving curative local superficial radiation (LSR) for minimal stage IA @entity6 . All @entity0 had pathologic documentation at diagnosis and at the time of suspected recurrences and no @entity0 received prior radiation. Ten @entity0 were treated with 100-280 Kv (A1), and 11 with 4-12 Mev electrons. Nine @entity0 had failed prior therapies ( @entity2 : 4; PUVA: 3; BCNU: 1; UVB: 1) and six received adjuvant therapy after completion of LSR (PUVA: 5; @entity2 : 1). Minimum follow-up was 1 year. RESULTS: The median follow-up was 36 months (13-246), and the median age when commencing LSR was 55 years (27-73). All @entity0 were Caucasian, and 11 were male. A total of 32 lesions were identified in 21 @entity0 ; 13 @entity0 had unilesional disease, 5 @entity0 had 2 lesions, and 3 had 3 lesions. A total of 33 fields were treated with a median treatment surface area of 107 cm2 (11-785). The median surface dose was 20 Gy (6-40), with 17 @entity0 receiving a dose > or = 20 Gy. The median fraction number was 5 for all fields, but was 10 for the fields receiving 20-40 Gy. The complete response rate was 97%, and all @entity0 were alive at last evaluation. All failures were cutaneous. One @entity0 had persistent disease (treated with 6 Gy), and three failed locally at 52 months (8 Gy), 16 months (20 Gy), and 4 months (20 Gy). None of these @entity0 received adjuvant therapy. Two @entity0 failed in distant skin sites and were salvaged. The actuarial DFS for the entire group at 5 and 10 years was 75 and 64%, respectively, with local control of 75% at both time intervals. For the 13 @entity0 with unilesional disease, the DFS was 85% at 10 years. For those treated with doses > or = 20 Gy, the DFS was 91% as was local control (no distant failures). @entity1 included mild erythema and dry desquamation acutely. Chronic @entity1 included @entity5 [2], and @entity7 [1]. No second cutaneous @entity4 was noted. CONCLUSION: @entity0 with minimal Stage IA @entity6 may be managed effectively with local superficial radiation alone without adjuvant therapy. Distant failure is unusual and @entity0 should receive a minimum surface dose of 20 Gy, which offers excellent local control. Sequalae of therapy are minimal.

title: Local superficial radiotherapy in the management of minimal stage IA XXXX ( @entity6 ).

answer: @entity3


abstract: UNASSIGNED: Acute exercise increases @entity1 uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase @entity1 uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased cell surface abundance of @entity4 . While increased proximal insulin signaling does not seem to mediate this effect, elevated phosphorylation of @entity5 , a downstream target of both insulin ( @entity3 ) and exercise (AMPK) signaling, appears to play a role. The main purpose of this study was to determine whether AMPK activation increases skeletal muscle insulin sensitivity. We found that prior AICAR stimulation of wild-type @entity0 muscle @entity2 to stimulate @entity1 uptake. However, this was not observed in @entity0 with reduced or ablated AMPK activity in skeletal muscle. Furthermore, prior AICAR stimulation enhanced insulin-stimulated phosphorylation of @entity5 at Thr(649) and Ser(711) in wild-type muscle only. These phosphorylation events were positively correlated with @entity1 uptake. Our results provide evidence to support that AMPK is sufficient to increase skeletal muscle insulin sensitivity. Moreover, @entity5 phosphorylation may facilitate the effect of prior AMPK activation to enhance @entity1 uptake in response to insulin.

title: Prior AICAR stimulation XXXX in @entity0 skeletal muscle in an AMPK-dependent manner.

answer: @entity2


abstract: PURPOSE: The 9p21 locus, encoding three important @entity1 suppressors ( @entity3 / @entity3 , @entity3 /ARF, and @entity6 / @entity6 ), is a major target of inactivation in the pathogenesis of many @entity0 @entity1 . @entity0 AND METHODS: To explore, at high resolution, the frequency and size of alterations affecting this locus in adult BCR-ABL1-positive @entity2 ( @entity2 ) and to investigate their prognostic value, 112 @entity0 (101 de novo and 11 relapsed cases) were analyzed by genome-wide single-nucleotide polymorphism arrays and gene candidate deep exon sequencing. Paired diagnosis-relapse samples were further available and analyzed for 19 (19%) cases. RESULTS: @entity3 and @entity6 genomic alterations were identified in 29% and 25% of newly diagnosed @entity0 , respectively. Deletions were monoallelic in 72% of cases, and in 43% of them, the minimal overlapping region of the lost area spanned only the @entity5 gene locus. An analysis conducted at relapse showed an increase in the detection rate of @entity3 /ARF loss (47%) compared with the time of diagnosis (P = 0.06). Point mutations within the 9p21 locus were found at very low levels, with only a nonsynonymous substitution in the exon 2 of @entity3 . Of note, deletions of @entity5 were significantly associated with poor outcomes in terms of overall survival (P = 0.0206), disease free-survival (P = 0.0010), and cumulative incidence of relapse (P = 0.0014). CONCLUSIONS: Inactivation of the 9p21 locus by genomic deletion is a frequent event in BCR-ABL1-positive @entity2 . Deletions are frequently acquired during @entity4 progression and are a poor prognostic marker of long-term outcomes.

title: @entity5 alterations impair prognosis in adult BCR-ABL1-positive XXXX @entity0 .

answer: @entity2


abstract: The concept of a @entity9 (such as @entity6 ) has always been controversial ( @entity8 , M.A. (1996). Somatization and conversion disorders. In: B.S. Fogel, R.B. Schiffer _ S.M. Rao (Eds.), @entity7 and Wilkins, Baltimore, @entity5 ). Although the diagnosis is recognised by current @entity2 taxonomies, many physicians still regard such disorders either as feigned or as failure to find the responsible organic cause for the @entity0 's symptoms. We report a @entity0 with left sided @entity6 (and without @entity4 ) in whom no @entity3 or structural lesion could be found. By contrast, psychological @entity1 was associated with the onset and recurrent exacerbation of her hemiparalysis. We recorded brain activity when the @entity0 prepared to move and tried to move her paralysed (left) leg and when she prepared to move and did move her good (right) leg. Preparing to move or moving her good leg, and also preparing to move her paralysed leg, activated motor and/or premotor areas previously described with movement preparation and execution. The attempt to move the paralysed leg failed to activate right primary motor cortex. Instead, the right orbito-frontal and right anterior cingulate cortex were significantly activated. We suggest that these two areas inhibit prefrontal (willed) effects on the right primary motor cortex when the @entity0 tries to move her left leg.

title: The functional anatomy of a XXXX .

answer: @entity6


abstract: Infections, @entity1 and @entity8 are the most important causes of @entity3 of unknown origin.A case report of a 80-year old @entity0 is described, who was admitted to our hospital because of @entity3 lasting more than 2 weeks, @entity5 and lack of appetite. Physical examination did not provide any relevant information, laboratory tests revealed an elevation of @entity2 markers and @entity6 . Serological tests for infectious and @entity8 and cultures of stool, blood and urine were all negative. Imaging did not show any pathological findings, colonoscopy and gastroscopy were macroscopically normal. Surprisingly, histology showed massive @entity9 of the duodenum. After initiation of therapy with @entity10 , @entity3 and @entity2 markers declined and the @entity0 could be discharged from hospital without complaints on the 15(th) day after admission. @entity7 is one of the most common intestinal pathogens worldwide. Infection can cause acute @entity4 , but may also be responsible for chronic abdominal complaints or may stay asymptomatic. To our knowledge, @entity9 has not been described as differential diagnosis of @entity3 of unknown origin so far. In synopsis of clinical presentation and outcome after antibiotic therapy, we postulate that @entity7 was the relevant cause of @entity3 and @entity5 in this case. In @entity0 presenting with these symptoms, @entity7 should be considered as differential diagnosis.

title: [Fever and @entity5 as leading symptoms of infection with XXXX ].

answer: @entity7


abstract: PURPOSE: Bone and soft-tissue defects in the leg can be caused by high-energy @entity2 . One of the causes of extensive @entity1 are @entity2 . The incidence of these has been noticeably increasing in recent years in countries with political instabilities due to the random availability of weapons. The aim of this study is to focus on the essentials of treatment of post-gunshot tibial bone loss using the Ilizarov concept. METHODS: In the period between June 2011 and July 2013, 30 @entity0 with open @entity3 after gunshots comprised the present study with an average follow-up of 18  months. The bone defect was associated with soft-tissue loss in 18 cases. All cases were subjected to extensive debridement of all devitalized tissues back to the healthy bone with viable soft tissue coverage. All cases were treated by the Ilizarov external fixator using the bifocal bone transport technique. RESULTS: The overall bone results were satisfactory in 28 cases (93.3  %). The overall functional results were satisfactory in 22 cases (73.3  %). The bone end results were significantly affected by age and smoking, while the functional end results were significantly affected by smoking, the presence of infection at the time of presentation, and complications during the procedure. CONCLUSIONS: Bone transport is a reliable method in the treatment of gunshot @entity1 of the tibia after extensive debridement of all the devitalized tissues. The Ilizarov external fixator allows the functional use of the limb throughout the course of treatment, preventing @entity4 and increasing @entity0 satisfaction.

title: Our experience in the management of segmental XXXX caused by gunshots.

answer: @entity1


abstract: The purpose of this study was to examine the effects of whey protein supplementation on @entity1 ( @entity4 ) metabolism and liver oxidative stress in @entity0 . Twenty-four @entity0 were divided into 3 groups (n = 8) to receive one of the following diets for 4 weeks: control diet (C), whey protein-composed diet (WP), and whey protein-supplemented diet (WPS). The C and WP diets consisted of AIN-93 with 20% casein and 20% whey protein as protein source, respectively. WPS was AIN-93 (20% casein) supplemented by the addition of 20% (w/w) whey protein. Four weeks of ingesting a WPS diet resulted in a significantly higher (P < 0.05) total protein and @entity2 intakes. Although a significant increase (P < 0.05) in the hepatic @entity5 and @entity7 levels occurred in WPS group compared with C and WP, no significant change was observed in plasma @entity4 concentration between groups. Furthermore, the levels of lipid @entity6 and advanced oxidation protein products, known liver oxidative stress markers, were increased in the WPS group compared with the C group. In addition, no change in @entity3 liver concentration was observed in any of the groups studied. In conclusion, whey protein supplementation increases @entity2 intake substantially; however, it does not change plasma @entity4 concentrations. On the other hand, increased hepatic oxidative stress markers were observed in whey protein supplemented @entity0 were probably due to high protein intake.

title: Whey protein supplementation increases @entity2 intake but not @entity1 plasma concentration in XXXX .

answer: @entity0


abstract: BACKGROUND: Previously, sponsored publications have shown that either @entity3 or @entity1 (pulse regimen) are effective for @entity0 with @entity2 . However, independent comparative studies are lacking. OBJECTIVES: To objectively compare treatment with @entity3 and @entity1 in @entity0 with @entity2 . METHODS: The effectiveness of @entity3 (250 mg/day 3 months) versus @entity1 pulse regimen (400 mg/day for the first week of each month, for three cycles) was retrospectively evaluated in @entity0 with @entity2 using mycological tests and subjective outcome measures. Statistical analyses were performed using one-way analyses of variance (ANOVA) for continuous variables and Fisher exact tests for categorical variables. RESULTS: Included in the study were 117 @entity0 (74 @entity0 treated by @entity3 and 43 @entity0 treated with @entity1 ). @entity0 were examined at an average period of 20 months after the end of therapy. Mycological cure was observed in 70.6% and 62.8% of the @entity0 who were treated by @entity3 or @entity1 , respectively (not statistically significant). Mean visual analogue scale assessment of treatment outcome was 79.9 mm (SD 24.7 mm) and 65.2 mm (SD 34.6 mm) for @entity0 treated by @entity3 or @entity1 , respectively (p=0.008). When the results were stratified according to age and gender, it was observed that the advantage of @entity3 versus @entity1 retained statistical significance only for @entity0 who were 55 years old and above, or females. CONCLUSIONS: Mycological cure proportions were not statistically significant between @entity0 treated by @entity3 or @entity1 for @entity2 . However, better subjective outcome measures indicated an advantage for @entity3 over @entity1 , noticeable in females and @entity0 55 years old and above.

title: An independent comparison of @entity3 and @entity1 in the treatment of XXXX .

answer: @entity2


abstract: IMPORTANCE AND BACKGROUND:: @entity5 ( @entity5 ) palsy and perineural invasion (PNI) are adverse features in @entity2 of the parotid gland. @entity5 sacrifice at the time of surgery is associated with significant morbidity. The role of adjuvant radiotherapy in @entity0 with high-risk features, including @entity5 involvement, remains unclear. OBJECTIVE:: Analyze the disease-free survival (DFS) and @entity4 ( @entity4 ) and the impact of @entity1 characteristics, including @entity5 involvement, for @entity0 treated with surgical resection for @entity2 . DESIGN:: This is a retrospective chart review. SETTING:: University of Utah and Intermountain Healthcare, Utah. @entity0 :: A total of 129 @entity0 who were treated with primary surgery for nonmetastatic primary malignancies of the parotid gland from 1988 to 2006. INTERVENTIONS:: Parotidectomy with or without adjuvant therapy. MAIN OUTCOME(S) AND MEASURES:: Kaplan-Meier analysis was used to obtain 5-year estimates of DFS and @entity4 . Recurrence risk factors, particularly the impact of @entity5 involvement, were analyzed. RESULTS:: Five-year DFS and @entity4 rates were 79% and 78%, respectively. Thirty-two (28%) @entity0 developed recurrent disease. Disease recurrence occurred in 64% of @entity0 with both @entity5 and PNI, in 43% with @entity5 without PNI, in 27% with only PNI, and in 16% without either feature. CONCLUSIONS AND RELEVANCE:: @entity5 involvement, particularly @entity5 , is a predictor of increased risk of recurrence and @entity3 . Radiotherapy cannot substitute for @entity5 sacrifice in high-risk @entity0 .

title: The Prognostic Significance of Facial Nerve Involvement in XXXX of the Parotid Gland.

answer: @entity2


abstract: OBJECTIVE: To examine trajectories of @entity1 in caregivers of critically ill adults from intensive care unit admission to 2 months postintensive care unit discharge and explore @entity0 and caregiver characteristics associated with differing trajectories. DESIGN: Longitudinal descriptive study. SETTING: Medical intensive care unit in a tertiary university hospital. SUBJECTS: Fifty caregivers and 47 @entity0 on mechanical ventilation for >= 4 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Caregivers completed measures assessing @entity1 (Short version Center for Epidemiologic Studies-Depression Scale 10-items), burden (Brief Zarit Burden Interview), and health risk behaviors (caregiver health behaviors) during intensive care unit admission, at intensive care unit discharge, and 2 months postintensive care unit discharge. Group-based trajectory analysis was used to identify patterns of change in shortened Center for Epidemiologic Studies-Depression Scale scores over time. Two trajectory groups emerged: 1) caregivers who had clinically significant @entity1 (21.0  4.1) during intensive care unit admission that remained high (13.6  5) at 2 months postintensive care unit discharge (high trajectory group, 56%); and 2) caregivers who reported scores that were lower (10.6  5.7) during intensive care unit admission and decreased further (5.7  3.6) at 2 months postintensive care unit discharge (low trajectory group, 44%). Caregivers in the high trajectory group tended to be younger, female, an adult @entity0 living with financial difficulty, and less likely to report a religious background or preference. More caregivers in the high trajectory group reported greater burden and more health risk behaviors at all time points; @entity0 tended to be male with poorer functional ability at intensive care unit discharge. Caregivers' responses during intensive care unit admission did not differ in regard to number of days @entity0 were on mechanical ventilation before enrollment. CONCLUSION: Findings suggest two patterns of depressive symptom response in caregivers of critically ill adults on mechanical ventilation from intensive care unit admission to 2 months postintensive care unit discharge. Future studies are necessary to confirm these findings and implications for providing caregiver support.

title: Patterns of XXXX in caregivers of mechanically ventilated critically ill adults from intensive care unit admission to 2 months postintensive care unit discharge: a pilot study.

answer: @entity1


abstract: Systemic corticosteroids (CS) are often used in treatment of @entity1 and are usually considered the main cause of @entity3 in @entity0 with @entity1 . The aim of this paper was to assess the influence of CS on development of @entity3 in @entity1 . In this study @entity2 ( @entity2 ) was analyzed in 43 @entity0 with @entity1 . Most of the examined @entity0 (72.1%) used CS for more than 3 months. @entity3 was diagnosed in 30.2% of @entity0 , and @entity4 in 44.2% of @entity0 . There were no statistically significant difference in @entity2 among @entity0 who were on CS and the ones who were not. In the group of newly diagnosed @entity0 60% had reduced bone density, opposing 61.6% of @entity0 with previously diagnosed disease. There was no statistically significant difference among those two groups of @entity0 . Risk factor such as corticosteroid therapy is not independent risk factor for reduced @entity2 . Newly diagnosed @entity0 have high prevalence of reduced @entity2 and they were not on CS therapy, which suggest that possible inflammatory nature of the disease is a possible risk factor for reduced @entity2 in @entity1 .

title: [The influence of corticosteroid therapy on development of @entity3 in XXXX ].

answer: @entity1


abstract: Management of @entity3 often includes oral opioid use. The effectiveness of therapy is dependent upon compliance, which in turn is dependent upon response, side effects, access, and convenience. Our hypothesis was that a transdermal @entity4 system would provide more effective @entity1 management than oral opioids. Fifty @entity0 with @entity3 were examined. After litration to levels corresponding to current oral opioid use, each @entity0 was maintained on transdermal @entity4 for one month. Oral opioid therapy was then resumed. Their experience was assessed with the a visual analogue scale for @entity1 intensity, a numerical @entity1 score, the @entity2 questionnaire, the @entity1 disability index, and the Verran Snyder-Halpern sleep scale. Significant improvement in @entity1 was found with transdermal @entity4 compared with oral opioids. Mild opioid side effects were common, but easily controlled. Use of transdermal @entity4 is an effective alternative to oral opioids for managing @entity3 .

title: Transdermal XXXX as treatment for @entity3 .

answer: @entity4


abstract: BACKGROUND: Appropriate @entity0 selection is very important when initiating mild @entity3 (MTH) for @entity0 following out-of-hospital @entity2 , and the extent of unconsciousness at implementation must be defined in such cases. However, there are no clear standards regarding the level of unconsciousness at which MTH would be beneficial. The effects of MTH in @entity0 with different degrees of unconsciousness according to the motor response score of the Glasgow @entity1 Scale (GCS) were investigated. METHODS: The subjects consisted of witnessed non-traumatic adult out-of-hospital @entity2 @entity0 admitted to our institute from April 2002 to August 2011. The @entity0 were divided into six groups according to the GCS motor response score: 1 (GCS M1), 2 (GCS M2), 3 (GCS M3), 4 (GCS M4), 5 (GCS M5), and 6 (GCS M6). The neurological outcome was evaluated at 30  days after hospital admission using the Cerebral Performance Category. @entity4 ( @entity4 ) analysis was performed to estimate the threshold GCS M level where @entity3 is indicated. Odds ratios were then calculated by multiple logistic-regression analysis using factors including GCS M5-6 and MTH. RESULTS: A total of 289 @entity0 were enrolled in this study. @entity4 analysis demonstrated two points of significant increase in percentage of good recovery at 30  days after admission, dividing the GCS M categories into three groups. @entity0 classified with a GCS motor response score of 5 or higher had the highest percentage of good recovery. The odds ratio for good recovery (CPC1-2) was 2.901 (95  % CI 1.460-5.763, P   =   0.002) for MTH, and that for GCS M5-6 was 159.835 (95  % CI 33.592-760.513, P   <   0.001). CONCLUSIONS: MTH may be unnecessary in @entity0 with a GCS motor response score of 5 or higher. Consequently, because there are post @entity2 @entity0 with a GCS motor response score of 4 or lower who benefit from MTH, MTH may be limited to @entity0 with a GCS motor response score of 4 or lower.

title: At what level of unconsciousness is mild XXXX indicated for out-of-hospital @entity2 : a retrospective, historical cohort study.

answer: @entity3


abstract: @entity5 in @entity4 has been recognized to be morphologically heterogenous, featuring adenomatous, foveolar, and hybrid phenotypes. Recent studies have suggested a @entity0 suppressor role for @entity11 in the @entity3 sequence. The phenotypic stability and role of @entity11 in the @entity0 progression of different types of @entity5 have not been evaluated. Thirty-eight endoscopic mucosal resections with @entity5 and/or @entity3 ( @entity3 ) arising in @entity4 were evaluated for the expression of @entity9 , @entity12 , @entity10 , @entity8 , and @entity11 . The background mucosa was also evaluated. The results were correlated with morphologic classification and clinicopathologic parameters. Of 38 endoscopic mucosal resections, 23 had @entity3 and @entity5 , 8 had @entity3 only, and 7 had @entity5 only. Among @entity1 , 73% were foveolar, 17% were adenomatous, and 10% were hybrid. Twenty of 23 cases with @entity5 and adjacent @entity3 showed an identical immunophenotype of @entity5 and @entity3 comprising 16 gastric, 3 intestinal, and 1 mixed immunophenotype. Three cases showed discordance of @entity5 and @entity3 immunophenotype. These findings suggest that most Barrett-related @entity3 cases are either gastric or intestinal, with phenotypic stability during progression supporting separate gastric and intestinal pathways of @entity2 . @entity11 showed gradual downregulation of expression during progression in @entity6 but not in foveolar or hybrid @entity5 , supporting a @entity0 suppressor role, at least in the intestinal pathway. @entity11 was also found to be expressed to a greater degree in @entity7 compared with nonintestinalized columnar metaplasia. Consistent with @entity11 as a @entity0 suppressor, this suggests that nonintestinalized columnar metaplasia may be an unstable intermediate state at risk for @entity0 progression.

title: Divergent expression of @entity9 , @entity12 , @entity10 , @entity8 , and @entity11 in XXXX and intramucosal adenocarcinomas with intestinal and foveolar morphology: is this evidence of distinct gastric and intestinal pathways to @entity2 in @entity4 ?

answer: @entity5


abstract: AIMS/HYPOTHESIS: Retinal M  ller cells are known to produce inflammatory and angiogenic cytokines, which play important roles in @entity0 . @entity6 -inducible factor (HIF)-1 has been shown to play a crucial role in retinal @entity3 and neovascularisation. We sought to determine the role of M  ller cell-derived HIF-1 in @entity2 -induced @entity7 (OIR) and @entity0 using conditional @entity9 (also known as @entity9 ) knockout (KO) @entity1 . METHODS: Conditional @entity9 KO @entity1 were generated by crossing @entity1 expressing cyclisation recombinase (cre, also known as P1_gp003) in M  ller cells with floxed @entity9 @entity1 and used for OIR and @entity11 -induced @entity0 to induce @entity10 and @entity3 , respectively. Abundance of @entity9 and pro-angiogenic and pro-inflammatory factors was measured by immunoblotting and immunohistochemistry. @entity10 was visualised by angiography and quantified by counting pre-retinal nuclei. Retinal @entity3 was evaluated by @entity5 . RESULTS: While the @entity9 KO @entity1 showed significantly decreased @entity9 levels in the retina, they exhibited no apparent histological or @entity4 under normal conditions. Compared with wild-type counterparts, @entity9 KO @entity1 with OIR demonstrated attenuated overproduction of @entity8 ( @entity8 ) and @entity12 , reduced vascular leakage and alleviated neovascularisation in the retina. Under @entity0 conditions, disruption of @entity9 in M  ller cells attenuated the increases of @entity7 and adherent leucocytes, as well as the overproduction of @entity8 and @entity12 . CONCLUSIONS/INTERPRETATION: M  ller cell-derived @entity9 is a key mediator of @entity10 , vascular leakage and @entity3 , the major pathological changes in @entity0 . M  ller cell-derived @entity9 is therefore a promising therapeutic target for @entity0 .

title: Ischaemia-induced @entity10 and @entity0 in @entity1 with conditional knockout of XXXX -inducible factor-1 in retinal M  ller cells.

answer: @entity6


abstract: Hypothalamic leptinoceptive neurones can be visualized by histochemical demonstration of @entity3 -induced nuclear translocation of the signalling molecule @entity4 . We investigated the relationship of the leptinoceptive neurones to the @entity2 signalling system. With double-labelling immunohistochemistry, we studied the colocalization of @entity3 -activated transcription factor, @entity4 , with @entity2 receptor subtypes, sst1, sst2A, sst2B, sst3 and sst4, or the neuropeptide itself, in the @entity0 hypothalamus. Immunoreactivity for all the entities was widely distributed throughout the entire hypothalamus. Despite the wide distribution, only few cases of colocalization of @entity2 with @entity3 -activated @entity4 were detected in the paraventricular, arcuate and dorsomedial nuclei. A moderate to high degree of colocalization of nuclear @entity4 and all investigated subtypes of @entity2 receptors was found in the lateral and dorsal @entity1 areas and in the dorsomedial @entity1 nucleus. Immunoreactivity for sst1, sst2B and sst4 was present in @entity4 -containing nuclei of the paraventricular, periventricular, arcuate and ventromedial @entity1 neurones, as well as in the retrochiasmatic and posterior @entity1 areas. Despite the wide distribution of sst2A in the @entity0 hypothalamus, few events of colocalization with @entity3 -activated @entity4 were observed in the dorsomedial nucleus and in the lateral and dorsal @entity1 areas only. Many @entity3 -responsive neurones of the dorsal, lateral, periarcuate, perifornical and posterior @entity1 areas, as well as in the ventromedial and dorsomedial @entity1 nuclei, displayed sst3 immunoreactivity at their neuronal cilia. These results provide strong anatomical evidence for the direct interaction of @entity3 and the @entity2 systems in neuroendocrine control loops such as the energy homeostasis, growth or stress response.

title: @entity3 -target neurones of the @entity0 hypothalamus express XXXX receptors.

answer: @entity2


abstract: The @entity0 tissue kallikrein family (KLK for protein; KLK for gene) includes 15 members. Twelve kallikreins, including @entity4 , are concurrently upregulated in @entity1 . However, the mechanism of this phenomenon remains unclear. In this study, we measured @entity4 expression in a large series of ovarian tissue cytosols and examined possible mechanisms of @entity4 up-regulation in @entity1 . Using a newly developed enzyme-linked immunosorbent assay (ELISA) with two monoclonal antibodies, we quantified @entity4 expression in ovarian tissue cytosols, and confirmed the upregulation of @entity4 in @entity1 and its unfavourable prognostic value. We then examined @entity4 mRNA expression using reverse transcription-polymerase chain reaction and established its good concordance with @entity4 protein expression. This finding suggested that the @entity4 gene is under transcriptional regulation. We then scrutinised a few mechanisms that could explain @entity4 upregulation. The relative abundance of two @entity4 mRNA transcripts was studied; we found the same differential expression pattern in all samples, regardless of @entity4 levels. Genomic mutation screening of all exons and the 5'-flanking region of the @entity4 gene identified two linked single- @entity3 polymorphisms in the 5'-untranslated region, but neither correlated with @entity4 expression. Ovarian cell lines were separately treated with five @entity2 hormones. None of the treatments produced significant effects on @entity4 expression. We conclude that @entity4 is transcriptionally upregulated in @entity1 , but probably not through alternative mRNA transcript expression, genomic mutation, or @entity2 hormone induction.

title: Transcriptional upregulation of @entity0 tissue kallikrein 6 in XXXX : clinical and mechanistic aspects.

answer: @entity1


abstract: AIM: To demonstrate the various patterns of @entity5 ( @entity5 ) around the shoulder and to discuss a therapeutic algorithm. METHOD: In this retrospective study, 6 @entity0 with histologically proven @entity5 were operated on. The diagnosis was based on clinical examination, plain X-rays, ultrasonography and MRI in 5/6 @entity0 . Also, a histological examination was done in all cases. According to the localisation of the disease, surgery was done by endoscopy alone, endoscopy together with open surgery or direct open surgery. RESULTS: In one case each, we saw an isolated disease of the subacromial bursa or the gleno-humeral joint. In two cases, we found an intraarticular affection together with the biceps @entity3 . The other two @entity0 showed a massive periarticular deposition of loose bodies together with a defect of the rotator cuff. All @entity0 with @entity1 (5/6) showed different stages of @entity4 . In 5 of 6 @entity0 all bodies could be removed at surgery. At follow-up after 36 months the @entity0 subjectively rated the result as satisfactory to excellent. In the @entity0 with total removal of the bodies, no recurrences were seen on plain X-ray or ultrasonography. CONCLUSION: @entity5 around the shoulder appears with a variable pattern. According to the possible late complications described in the literature (i. e., secondary @entity2 , involvement of the rotator cuff and secondary malignant transformation), we find operative treatment justified. Surgery addressing removal of loose bodies and partial synovectomy allows good results. The operative approach (endoscopy or open surgery) is related to the localisation and severity of the condition.

title: [Primary XXXX of the shoulder].

answer: @entity5


abstract: The May 2003 COM. A 57-year-old @entity0 presented with slurring of her speech and right arm weakness. Her past medical history included @entity3 ( @entity3 ), @entity6 , @entity5 , @entity8 , @entity2 and @entity13 . Neurological examination showed persistent word finding difficulty but her motor and sensory function had essentially returned to normal. Extensive laboratory studies were unrevealing. Imaging studies showed a @entity7 over the left posterior parietal lobe and the findings suggested an @entity4 or inflammatory process. A biopsy of the involved dura and meninges was performed and revealed @entity17 . Emperipolesis was noted. The finding of emperipolesis is characteristic of @entity17 , but in 30% of cases, this feature will not be identified. Large pale histiocytes of @entity17 are immunoreactive for @entity14 protein and KP1, but negative for @entity16 . The differential diagnosis of a chronic inflammatory infiltrate containing numerous, large histiocytes includes @entity9 such as @entity15 and @entity11 , and Langerhans @entity18 . CNS Rosai-Dorfman most commonly involves @entity0 between 20- and 40-years-old, with a slight male predominance. Approximately 75% of cases are intracranial, whereas 20% involve the spine. Over 90% of CNS Rosai-Dorfman cases involve the leptomeninges and are seen by neuroimaging as a dural-based, contrast-enhancing masses that often elicit vasogenic @entity1 in the underlying brain. Thus, clinically and radiologically, the disease is thought to represent @entity12 . Leptomeningeal @entity17 is considered a benign condition and in most cases surgical resection is the treatment of choice. Although the number of cases in the literature is small, disease progression following surgical resection is uncommon. Little is known regarding the pathogenesis of @entity17 . Most have suggested that it represents either an @entity10 or a reaction to an @entity4 agent that has yet to be discovered. Currently it is best considered a benign, idiopathic @entity18 .

title: May 2003: 57-year-old- XXXX with acute loss of strength in her right upper extremity and slurred speech.

answer: @entity0


abstract: BACKGROUND: Management of severe @entity5 (SAC) complicating @entity1 remains a challenge despite significant advances in medical therapy. The aim of this study was to report a 20-year experience with subtotal colectomy (STC) performed for SAC. STUDY DESIGN: A total of 164 consecutive @entity0 with a mean age of 37 +/- 15 years (range 16 to 86 years) underwent STC for SAC defined according to the criteria of Truelove and Witts. The decision for surgical treatment was based on clinical, biologic, radiologic, and endoscopic severity criteria both at entry and during hospitalization after failure to improve under medical treatment. A Brooke ileostomy was made to the right iliac fossa and a sigmoidostomy was made to the midline incision. All complications before discharge were recorded as in-hospital morbidity or mortality. RESULTS: Colonoscopy was performed in 153 @entity0 and endoscopic diagnosis of SAC was confirmed by pathologic examination in 84% of the cases. STC was performed on an emergency basis in 40 @entity0 with complications and only after failure of medical treatment in the remaining 124 @entity0 . The mortality rate was 0.6%. The overall morbidity rate was 33%; 24 @entity0 required reoperation, including 8% undergoing reoperation during followup for @entity4 . Definitive pathologic diagnosis changed in one half of the @entity0 ; the final diagnosis was @entity2 in 110 cases, @entity3 in 35, and indeterminate @entity5 in 19. CONCLUSIONS: Our results demonstrated the safety of STC performed in a tertiary care center for @entity0 with SAC who presented with complications or failed to respond to intensive medical therapy.

title: Subtotal colectomy for severe XXXX : a 20-year experience of a tertiary care center with an aggressive and early surgical policy.

answer: @entity5


abstract: BACKGROUND: In @entity0 with @entity1 and multivessel disease, @entity4 bypass graft surgery and percutaneous coronary intervention are treatment options. However, there is paucity of data comparing @entity4 bypass graft surgery against newer generation stents. METHODS AND RESULTS: @entity0 included in the New York State registries who had @entity1 and underwent isolated @entity4 bypass graft surgery or percutaneous coronary intervention with @entity6 eluting stent (EES) for multivessel disease were included. Propensity score matching was used to assemble a cohort with similar baseline characteristics. The primary outcome was all-cause mortality. Secondary outcomes were @entity5 ( @entity5 ), @entity2 , and repeat revascularization. Short-term (within 30 days) and long-term outcomes were evaluated. Among 16   089 @entity0 with @entity1 and multivessel disease, 8096 @entity0 with similar propensity scores were included. At short-term, EES was associated with a lower risk of @entity3 (hazard ratio [HR] =0.58; 95% confidence interval [CI], 0.34-0.98; P=0.04) and @entity2 (HR=0.14; 95% CI, 0.06-0.30; P<0.0001) but higher risk of @entity5 (HR=2.44; 95% CI, 1.13-5.31; P=0.02). At long-term, EES was associated with a similar risk of @entity3 (425 [10.50%] versus 414 [10.23%] events; HR=1.12; 95% CI, 0.96-1.30; P=0.16), a lower risk of @entity2 (118 [2.92%] versus 157 [3.88%] events; HR=0.76; 95% CI, 0.58-0.99; P=0.04) but a higher risk of @entity5 (260 [6.42%] versus 166 [4.10%] events; HR=1.64; 95% CI, 1.32-2.04; P<0.0001) and repeat revascularization (889 [21.96%] versus 421 [10.40%] events; HR=2.42; 95% CI, 2.12-2.76; P<0.0001). The higher risk of @entity5 was not seen in the subgroup of EES @entity0 who underwent complete revascularization (HR=1.37; 95% CI, 0.76-2.47; P=0.30). CONCLUSIONS: In @entity0 with @entity1 and multivessel disease, EES was associated with lower upfront risk of @entity3 and @entity2 when compared with @entity4 bypass graft surgery. However, at long-term, EES was associated with similar risk of @entity3 , a higher risk of @entity5 (in those with incomplete revascularization), and repeat revascularization but a lower risk of @entity2 .

title: XXXX Eluting Stents Versus Coronary Artery Bypass Graft Surgery for @entity0 With @entity1 and Multivessel Disease.

answer: @entity6


abstract: PURPOSE: Recently laser-in-situ-keratomileusis (LASIK) has been increasingly used to correct @entity5 . The purpose of this investigation was to evaluate the safety, efficacy, predictability, stability and complications using the scanning spot excimer LASIK technology. @entity0 AND METHODS: The results of 100 consecutive LASIK operations carried out between 2/1998 and 2/1999 on 60 @entity0 (mean age 37 years, range 20-55 years) have been evaluated. The Hansatome microkeratome with a superior hinge (flap diameter: 9.5 mm) and a scanning spot excimer laser (Technolas C-Lasik 217) were used in all cases. The mean spherical equivalent of the subjective manifest refraction was -6.96 +/- 2.87 diopters (D), the mean sphere was -6.47 +/- 2.71 D and the mean @entity2 was -0.98 +/- 0.94 D. In 6% of the eyes preoperative visual acuity was not better than 20/40. Examinations were performed preoperatively, after 1 and 7 days, after 1,4 and 12 months. Safety, efficacy, predictability, stability and complications were calculated using the datagraph software (version 1.11). RESULTS: All 100 eyes were examined after 1 day and 1 week, 96 after 1 month, 95 after 4 months and 92 after 1 year. Following 1 year none of the eyes lost 2 or more lines of best corrected visual acuity, 99% were within +/- 1 line and 1% gained 2 lines (safety index 1.03). In 92% of all eyes an uncorrected visual acuity of > or = 0.5 was reached, in 77% > or = 0.8 and in 51% > or = 1.0 (efficacy index 0.89). For 60 eyes (65.21%) a refractive correction of +/- 0.5 D was necessary, for 82 eyes (89.13%) +/- 1.0 D and for 91 eyes (98.91%) +/- 2.0 D. The mean spherical equivalent after 1 year was -0.15 +/- 1.31 D. Between 1 and 12 months a mean regression of -0.14 D occurred. On the request of the @entity0 , 5 eyes were retreated during the study period for under- or over-correction. Complications due to the microkeratome did not occur. @entity1 were not observed, a @entity3 ( @entity3 ) was seen in 12 cases, but all cases healed with no loss of visual acuity. In 7 eyes a slight decentration of the ablation was observed using corneal topography, which in one case caused an increase in glare sensitivity. CONCLUSIONS: LASIK with superior hinge and scanning spot excimer photoablation is suitable for the correction of @entity4 (up to a maximum of -12 D) and for @entity2 (up to a maximum of -5 D). The refractive results showed a high stability during the 12-month study period but there is still room for improvement of the predictability.

title: [LASIK with a superior hinge and scanning spot excimer laser ablation for correction of @entity4 and XXXX . Results of a prospective study on 100 eyes with a 1-year follow-up].

answer: @entity2


abstract: @entity2 is characterized by massive degeneration of @entity3 -containing neurons in the midbrain. However, the vulnerability of these neurons is heterogeneous both across different midbrain @entity3 -containing cell groups and within the substantia nigra, the brain structure most affected in this disease. To determine the exact pattern of cell loss and to map the cellular distribution of candidate pathogenic molecules, it is necessary to have landmarks independent of the degenerative process by which to subdivide the substantia nigra. We have developed a protocol for this purpose based on immunostaining for calbindin D(28K), a protein present in striatonigral afferent fibres. We used it to examine post-mortem brain samples from seven subjects who had had no history of neurological or @entity1 disease. We found intense immunostaining for calbindin D(28K) associated with the neuropil of the ventral midbrain. Within the calbindin-positive region, there were conspicuous calbindin-poor zones. Analysed in serial sections, many of the calbindin-poor zones seen in individual sections were continuous with one another, forming elements of larger, branched three-dimensional structures. Sixty per cent of all @entity3 -containing neurons in the substantia nigra pars compacta were located within the calbindin-rich zone, which we named the nigral matrix, and 40% were packed together within the calbindin-poor zones, which we named nigrosomes. We identified five different nigrosomes. This organization was consistent from one control brain to another. We propose that subdivision of the @entity0 substantia nigra based on patterns of calbindin immunostaining provides a key tool for analysing the organization of the substantia nigra and offers a new approach to analysing molecular expression patterns in the substantia nigra and the specific patterns of nigral cell degeneration in @entity2 .

title: The substantia nigra of the XXXX brain. I. Nigrosomes and the nigral matrix, a compartmental organization based on calbindin D(28K) immunohistochemistry.

answer: @entity0


abstract: BACKGROUND: Neoadjuvant systemic chemotherapy is being increasingly used prior to liver resection for colorectal @entity1 . Oxaliplatin has been implicated in causing structural changes to the @entity3 , and such changes may increase the morbidity and mortality of surgery. @entity0 AND METHODS: A retrospective study was undertaken of 101 consecutive @entity0 who had undergone liver resection for colorectal @entity1 in two HPB centers. Preoperative demographic and premorbid data were gathered along with liver function tests and @entity2 markers. A subjective assessment of the surgical procedure was noted, and in-hospital morbidity and mortality were calculated. The effect of preoperative chemotherapy on short-term and long-term outcome was analyzed, and actuarial 1 and 3 year survival was determined. RESULTS: @entity0 who received neoadjuvant chemotherapy had a higher number of @entity1 (median 2, range 1-8 versus median 1, range 1-5; P = 0.019) and more had @entity2 (24 @entity0 versus 8; P < 0.001). Overall morbidity was 37% and hospital mortality was 3.9%. Operative and in-hospital outcome was not influenced by chemotherapy. Long-term survival was worse in @entity0 who had received preoperative chemotherapy (actuarial 3-year survival 62% versus 80%; P = 0.04). CONCLUSIONS: This study shows no evidence that neoadjuvant chemotherapy, and in particular @entity4 , increases the risk associated with liver resection for colorectal @entity1 . Long-term outcome is reduced in @entity0 receiving preoperative chemotherapy, although they have more @entity5 .

title: Preoperative chemotherapy and the outcome of liver resection for colorectal XXXX .

answer: @entity1


abstract: OBJECTIVE: We aimed to confirm the efficacy of @entity5 in Japanese postmenopausal @entity0 ( @entity0 ) @entity1 , and investigate factors contributing @entity4 ( @entity4 ) prolongation. RESEARCH DESIGN AND METHODS: This retrospective study included 194 @entity0 @entity1 who received @entity5 (500  mg) from January 2012 to December 2014. MAIN OUTCOME MEASURES: @entity4 (efficacy measure), overall survival (OS), factors prolonging @entity4 and adverse events were evaluated. RESULTS: The median age was 65 (42 - 90) years. Overall, @entity4 was 5.48 months. In @entity1 without prior chemotherapy (n  =  59), OS was significantly longer (p  =  0.0131) than in @entity1 with prior chemotherapy (n  =  135). There was no strong correlation between @entity4 with @entity5 and other endocrine therapies, total duration of endocrine therapy and maximum duration of endocrine therapy. @entity4 was significantly longer in @entity1 with less than two prior chemotherapy regimens (p  =  0.0093), de novo @entity2 (p  =  0.0124) and without liver @entity2 (p  =  0.0024). We observed one case each of @entity6 and @entity3 . CONCLUSIONS: @entity5 is effective for @entity0 @entity1 and may show greater efficacy in @entity1 with few prior chemotherapy regimens, de novo @entity2 and absence of liver @entity2 . Prior endocrine therapy duration might not be a predictive factor for @entity5 @entity4 in heavily treated @entity0 @entity1 .

title: Efficacy of XXXX 500 mg in Japanese postmenopausal @entity0 @entity1 and factors associated with prolonged time-to-treatment failure.

answer: @entity5


abstract: BACKGROUND: To investigate the efficacy and @entity1 of FOLFOX4 regimen and LV5Fu2 regimen in @entity0 with advanced @entity3 after curative gastrectomy. METHODS: Eighty @entity0 with @entity3 after curative gastrectomy were randomized to receive a 2-h infusion of leucovorin (LV; 200mg/m(2)/d) followed by a @entity8 ( @entity8 ) bolus (400mg/m(2)/d) and 22-h infusion (600 mg/m(2)/d) for 2 consecutive days every 2 weeks, either alone or together with @entity5 85 mg/m(2) as a 2-h infusion on day 1 (FOLFOX4 regimen or LV5Fu2 regimen). The observation points were recurrence free survival, overall survival and @entity1 of the two groups. RESULTS: All @entity0 had received curative gastrectomy (R0 resection) before received either of the two regimens. The 3-year recurrence free survival rate and the 3-year overall survival rate in FOLFOX4 group were all significantly better than those in the control group (median, 30.0 months vs. 16.0 months, P<0.05; 36.0 months vs. 28.0 months, P<0.05). COX multivariant analysis was used to evaluate the prognostic factors and @entity5 was found to be the independent prognostic factor and could improve the survival rate in FOLFOX4 group. Grade 3/4 @entity9 occurred in 19% in FOLFOX4 group. There was no significant difference between the two groups in @entity6 , @entity7 , @entity4 , @entity2 and so on. Three @entity0 in each group were lost to follow up during treatment. CONCLUSION: FOLFOX4 regimen showed good efficacy and an acceptable safety profile for @entity0 with advanced @entity3 after curative gastrectomy compared with the control group. It may prove to be a suitable alterative regimen in this indication.

title: Prospective, randomized trial comparing @entity8 /LV with or without XXXX as adjuvant treatment following curative resection of @entity3 .

answer: @entity5


abstract: BACKGROUND: Non-adherence to treatment in @entity0 with @entity1 is associated with increased hospitalization, higher health care costs, and poorer long-term outcomes in terms of relapse rates. It is established that a negative drug attitude was a risk factor for non-adherence in long-term @entity1 . The scale "Drug Attitude Inventory" is one of the scales designed to assess this concept. It has been translated and validated in different languages. However, its psychometric properties have not yet been studied in our sociocultural context. OBJECTIVES: The aims of this study were to translate into Tunisian Arabic dialect the scale "Drug Attitude Inventory" with 30 dichotomous items (DAI-30) and validate it in Tunisian sociocultural context in @entity0 with @entity1 . MATERIALS AND METHODS: This study was performed in 234 outpatients with @entity1 , recruited through a random drawing. These @entity0 are in remission and meet remission criteria proposed by "The Remission in @entity1 Working Group". We recruited 30 @entity0 for pretest and 204 @entity0 for linguistic validation. Forward and backward translation of the DAI-30 was performed according to the protocol of the "MAPI Research Institute". This final version was submitted to 24 experts and followed by a pretest. @entity2 has been established by performing a principal component analysis factor on a sample of 204 @entity0 . Internal consistency was assessed by Cronbach alpha coefficient and inter-rater reliability was assessed by the use of Intra-Class Correlation coefficient (ICC). For the test-retest reliability evaluation, the "r" @entity3 was used between the DAI scores obtained in the initial evaluation and those obtained at 15 days. RESULTS: Regarding construct validity, factor analysis revealed seven factors that were responsible for 59.9% of the variance. The study of internal consistency between the 30 items was rated good (a=0.88). The test-retest reliability was satisfactory (r=0.99, p<10(-3)), as well as inter-rater reliability (ICC=0.99). CONCLUSION: In the Tunisian cultural context, the DAI-30 presented seven factors with good consistency and an inter-rater reliability.

title: Cultural translation and Tunisian validation of the Drug Attitude Inventory (DAI-30) in outpatients with XXXX .

answer: @entity1


abstract: Two hybrid genes ( @entity4 -HuIFN-gamma2 and @entity4 -HuIFN-gamma3) were constructed on the basis of @entity3 @entity4 ( @entity4 ) and @entity0 @entity2 (HuIFN-gamma) gene sequences. They were used to direct HuIFN-gamma synthesis in the mammary gland of @entity1 . HuIFN-gamma was efficiently produced in the mammary gland of @entity1 . @entity4 -HuIFN-gamma2 transgenic females expressed HuIFN-gamma in the milk at concentrations up to 570 mg/ml, and @entity4 -HuIFN-gamma3 transgenic females expressed up to 350 mg/ml. All females carrying the @entity4 -HuIFN-gamma3 gene expressed HuIFN-gamma in their milk. No significant changes were observed in the HuIFN-gamma expression level during the lactation period. Using RT-PCR analysis, ectopic expression for both hybrid genes was found in @entity1 . Despite ectopic expression of HuIFN-gamma in @entity1 , their development and pregnancy were normal. The heritability of the HuIFN-gamma expression level in milk was demonstrated up to the F2 generation. This work demonstrates that hybrid genes have the potential to develop in transgenic domestic animals producing HuIFN-gamma in milk.

title: Efficient @entity0 XXXX expression in the mammary gland of @entity1 .

answer: @entity2


abstract: INTRODUCTION: @entity0 @entity8 ( @entity8 ) has been hypothesized to be an age-dependent disease accompanied by similar vascular changes in other organs. SHRSP feature numerous vascular risk factors and may be a valid model of some aspects of @entity0 @entity8 . Here we compare renal histopathological changes with the brain pathology of spontaneously @entity5 @entity3 -prone @entity2 (SHRSP). MATERIAL AND METHODS: We histologically investigated the brains and kidneys of 61 SHRSP at different stages of age (12 to 44 weeks). The brain pathology (aggregated erythrocytes in capillaries and arterioles, microbleeds, microthromboses) and the kidney pathology (aggregated erythrocytes within peritubular capillaries, tubular protein cylinders, @entity6 ) were quantified separately. The prediction of the brain pathology by the kidney pathology was assessed by creating ROC-curves integrating the degree of kidney pathology and age of SHRSP. RESULTS: Both, brain and kidney pathology, show an age-dependency and proceed in definite stages whereas an aggregation of erythrocytes in capillaries and arterioles, we parsimoniously interpreted as stases, represent the initial finding in both organs. Thus, early renal @entity1 characterized by rather few intravasal erythrocyte aggregations and tubular protein cylinders predicts the initial step of SHRSPs' cerebral vascular pathology marked by accumulated erythrocytes. The combined increase of intravasal erythrocyte aggregations and protein cylinders accompanied by @entity6 and @entity9 in kidneys of older SHRSP predicts the final stages of SHRSPs' @entity4 marked by microbleeds and @entity7 . CONCLUSION: Our results illustrate a close association between structural brain and kidney pathology and support the concept of small vessel disease to be an age-dependent systemic pathology. Further, an improved joined nephrologic and neurologic diagnostic may help to identify @entity0 with @entity8 at an early stage.

title: Kidney pathology precedes and predicts the pathological cascade of @entity4 in @entity3 prone XXXX .

answer: @entity2


abstract: @entity6 sphingomyelinase belongs to the @entity1 -dependent neutral sphingomyelinase, which hydrolyses @entity5 to @entity4 and @entity2 , and acts as an extracellular hemolysin. The triplet residues, His151- @entity3 195-His296, of the enzyme are highly conserved among bacterial and @entity0 @entity1 -dependent neutral sphingomyelinases. The triplet residues converge on the active-site pocket of the 3D model of the enzyme. To investigate the function of these residues in the acid-base catalysis, we introduced several mutations for each residue by site-directed mutagenesis. Hemolytic and hydrolytic activities of the enzyme, abolished by the mutations at @entity3 195 and His296, revealed that these residues are critical for the catalytic function. The effect of the divalent metal cations on the pH dependency of the hydrolytic activities indicates that His296 corresponds to the most acidic ionizable group as a general base. The mutagenesis at His151 was also deleterious; however, the @entity7 and @entity8 mutant enzymes partially retained their activities. The @entity7 mutation affected the most basic ionizable group, suggesting that His151 may act as a general acid in catalysis. By the structural basis of the 3D model, @entity3 195 must maintain not only the appropriate spatial arrangement but also pK(a)s of His151 and His296. Taking into consideration all of these, we proposed the acid-base catalytic mechanism of @entity6 sphingomyelinase.

title: His151 and His296 are the acid-base catalytic residues of XXXX sphingomyelinase in sphingomyelin hydrolysis.

answer: @entity6


abstract: Messenger @entity3 encoding the alpha-subunit of @entity1 /calmodulin-dependent protein kinase II (camkII) is abundantly and constitutively expressed in dendrites of pyramidal and granule cell neurons of the adult hippocampus. Recent evidence suggests that camkII messenger @entity3 is stored in a translationally dormant state within @entity3 storage granules. Delivery of camkII messenger @entity3 from sites of storage to sites of translation may therefore be a key step in activity-driven dendritic protein synthesis and synaptic plasticity. Here we explored possible camkII trafficking in the context of long-term potentiation in the dentate gyrus of awake, adult @entity0 . Long-term potentiation was induced by patterned high-frequency stimulation, synaptodendrosomes containing pinched-off dendritic spines were obtained from microdissected dentate gyrus, and messenger @entity3 levels were determined by real-time polymerase chain reaction. High-frequency stimulation triggered a rapid 2.5-fold increase in camkII messenger @entity3 levels in the synaptodendrosome fraction. This increase occurred in the absence of camkII upregulation in the homogenate fraction, indicating trafficking of pre-existing messenger @entity3 to synaptodendrosomes. The elevation in camkII messenger @entity3 was paralleled by an increase in protein expression specific to the synaptodendrosome fraction, and followed by depletion of camkII message. Activity-dependent regulation of camkII messenger @entity3 and protein did not require @entity2 receptor activation. In contrast, @entity2 receptor activation was required for induction of the immediate early genes @entity4 and activity-regulated cytoskeleton-associated protein in dentate gyrus homogenates. The results support a model in which locally stored camkII messenger @entity3 is rapidly transported to dendritic spines and translated during long-term potentiation in behaving @entity0 .

title: Bursts of high-frequency stimulation trigger rapid delivery of pre-existing alpha-CaMKII mRNA to synapses: a mechanism in dendritic protein synthesis during long-term potentiation in adult awake XXXX .

answer: @entity0