The purpose of this study was to determine the reliability of screening for medication adherence in HIV-infected children. The results suggest that caregivers who are unable to describe the ...medication regimen or who are nonadherent with appointments are unlikely to adhere to the medication regimen. Adherence with at least 90% of medication doses was associated with a virologic response.
Background This study tested the hypothesis that microstructural white matter abnormalities in frontostriatal-limbic tracts are associated with poor response inhibition on the Stroop task in ...depressed elders. Method Fifty-one elders with major depression participated in a 12-week escitalopram trial. Diffusion tensor imaging was used to determine fractional anisotropy (FA) in white matter regions. Executive function (response inhibition) was assessed with the Stroop task. Voxelwise correlational analysis was used to examine the relationship between Stroop performance and fractional anisotropy. Results Significant associations between FA and Stroop color word interference were evident in multiple frontostriatal-limbic regions, including white matter lateral to the anterior and posterior cingulate cortex and white matter in prefrontal, insular, and parahippocampal regions. Conclusions These findings suggest that microstructural white matter abnormalities of frontostriatal-limbic networks are associated with executive dysfunction of late-life depression. This observation provides the rationale for examination of specific frontostriatal-limbic pathways in the pathophysiology of geriatric depression.
The synthesis, structure-activity relationships, and biological properties of a novel series of imidazole-containing inhibitors of farnesyltransferase are described. Starting from a ...3-aminopyrrolidinone core, a systematic series of modifications provided 5h, a non-thiol, non-peptide farnesyltransferase inhibitor with excellent bioavailability in dogs. Compound 5h was found to have an unusually favorable ratio of cell potency to intrinsic potency, compared with other known FTIs. It exhibited excellent potency against a range of tumor cell lines in vitro and showed full efficacy in the K-rasB transgenic mouse model.
An orally active, nonpeptide Arg‐Gly‐Asp (RGD) mimetic αvβ3 antagonist, (S)‐3‐Oxo‐8‐2‐6‐(methylamino)pyridin‐2‐yl‐1‐ethoxy‐2‐(2,2,2‐trifluoroethyl)‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine‐4‐acetic acid ...(compound 1), has been generated, which prevented net bone loss and inhibited cancellous bone turnover in vivo. The compound binds αvβ3 and the closely related integrin αvβ5 with low nanomolar affinity but binds only weakly to the related integrins αIIbβ3, and α5β1. Compound 1 inhibited αvβ3‐mediated cell adhesion with an IC50 = 3 nM. More importantly, the compound inhibited human osteoclast‐mediated bone resorption in vitro with an IC50 = 11 nM. In vivo, compound 1 inhibited bone resorption in a dose‐dependent fashion, in the acute thyroparathyroidectomized (TPTX) rat model of bone resorption with a circulating EC50 ∼ 20 μM. When dosed orally at 30 mg/kg twice a day (b.i.d.) in the chronic ovariectomy (OVX)‐induced rat model of osteopenia, compound 1 also prevented bone loss. At doses ranging from 3 to 30 mg/kg b.i.d., compound 1 partially prevented the OVX‐induced increase in urinary deoxypyridinoline. In addition, the compound prevented the OVX‐induced reduction in cancellous bone volume (BV), trabecular number (Tb.N), and trabecular thickness (Tb.Th), as assessed by quantitative microcomputerized tomography (μCT) and static histomorphometry. Furthermore, both the 10‐mg/kg and 30‐mg/kg doses of compound prevented the OVX‐induced increase in bone turnover, as measured by percent osteoid perimeter (%O.Pm). Together, these data indicate that the αVβ3 antagonist compound 1 inhibits OVX‐induced bone loss. Mechanistically, compound 1 prevents bone loss in vivo by inhibiting osteoclast‐mediated bone resorption, ultimately preventing cancellous bone turnover.
In a sample of students referred to a school-based Pupil Assistance Committee, the Inattention and Hyperactivity-Impulsivity factors of the Attention Deficit Hyperactivity Disorder (ADHD) Rating ...Scale-IV were used to predict diagnostic status, determined by a parent-reported diagnostic interview and teacher rating scale. Results of logistic regression and receiver operating curve analyses indicated that the Inattention and Hyperactivity-Impulsivity factors differentiated students with ADHD from controls and distinguished children with different ADHD subtypes. Symptom utility estimates demonstrated that a single informant approach was best suited for ruling out ADHD, whereas a combined informant method was optimal for positively diagnosing this disorder. Methods for determining the incremental utility of combining teacher with parent reports were demonstrated.
We investigated interactions between genetic and psychological factors in predicting shoulder impairment phenotypes. We hypothesized that pro-inflammatory genes would display stronger relationships ...compared with pain-related genes when combined with psychological factors for predicting phenotypic changes.
Altogether, 190 participants completed a 5-day experimental protocol. An experimental shoulder injury model was used to induce physical impairment, and a priori selected genetic (pain-related, pro-inflammatory) and psychological (anxiety, depressive symptoms, pain catastrophizing, fear of pain, kinesiophobia) factors were included as predictors of interest. Impairment phenotypes were injury-induced deficits in range of motion (ROM) and strength. After controlling for age, sex, and race, genetic and psychological predictors were entered separately as main effects and interaction terms in regression models for each phenotype.
Strong statistical evidence was provided for interactions between: 1) IL-1β (rs1143634) and fear of pain for predicting loss of shoulder flexion and abduction, 2) IL-1β (rs1143634) and anxiety for predicting loss of flexion, and 3) IL-1β (rs1143634) and depressive symptoms for predicting loss of internal rotation. In addition, the interaction between OPRM1 (rs1799971) and fear of pain as well as COMT (rs4818) and pain catastrophizing provided strong statistical evidence for predicting strength loss.
Pro-inflammatory gene variants contributed more to physical impairment with two single nucleotide polymorphisms (SNPs; IL-1β rs1143634 and TNF/LTA rs2229094) interacting with psychological factors to predict six shoulder impairment phenotypes. In comparison, two pain-related gene SNPs (OPRM1 rs1799971 and COMT rs4818) interacted with psychological factors to predict four shoulder impairment phenotypes (abduction: 5-day average loss; strength loss: 5-day average, peak, and relative loss).
Most studies of Alzheimer's disease (AD) have focused on a single precipitating alteration as the etiological event rather than global changes closely linked to aging. Recent evidence suggests that ...the most significant of these global changes are metabolic. Here we present data indicating that metabolic rate, nutrition, and neuronal size are all early indicators of AD. Understanding the cellular and molecular basis for these changes may open a new dimension to understanding AD.
Objectives To describe the spectrum of axillary artery pathology seen in high-performance overhead athletes and the outcomes of current treatment. Methods A retrospective review of patients that had ...undergone management of axillary artery lesions in a specialized center for thoracic outlet syndrome (TOS). Treatment outcomes were assessed with respect to arterial pathology and operative management. Results Nine male athletes were referred for arterial insufficiency in the dominant arm between January 2000 and August 2010, representing 1.6% of 572 patients treated for TOS (19% of 47 patients treated for arterial TOS). Seven were elite baseball pitchers (six professional, one collegiate), and two were professional baseball coaches with practice pitching responsibilities, with a mean age of 30.9 ± 2.9 years. Presenting symptoms included arm fatigue (five), finger numbness (four), cold hypersensitivity/Raynaud's (two), rest pain (one), and cutaneous fingertip embolism (one). Three patients underwent transcatheter thrombolysis prior to referral, including one with angioplasty and stenting. At angiography and surgical exploration 2.5 ± 0.8 weeks after symptom presentation (range, 1-8 weeks), six patients had occlusion of the distal axillary artery opposite the humeral head either at rest (three) or with arm elevation (three), one had axillary artery dissection with positional occlusion, and two had thrombosis of circumflex humeral artery aneurysms. Five patients had embolic arterial occlusions distal to the elbow. Treatment included segmental axillary artery repair with saphenous vein (n = 7; five interposition bypass grafts and two patch angioplasties), ligation/excision of circumflex humeral artery aneurysms (n = 2), and distal artery thrombectomy/thrombolysis (n = 2). Mean postoperative hospital stay was 3.8 ± 0.5 days, and the time until resumption of unrestricted overhead throwing was 10.8 ± 2.7 weeks. At a median follow-up of 15 months (range, 3-123 months), primary-assisted patency was 89%, and secondary patency was 100%. All nine patients had continued careers in professional baseball, although one retired during long-term follow-up. Conclusions Repetitive positional compression of the axillary artery can cause a spectrum of pathology in the overhead athlete, including focal intimal hyperplasia, aneurysm formation, segmental dissection, and branch vessel aneurysms. Prompt recognition of these rare lesions is crucial given their propensity toward thrombosis and distal embolism, with positional arteriography necessary for diagnosis. Full functional recovery can usually be anticipated within several months of surgical treatment, consisting of mobilization and segmental reconstruction of the diseased axillary artery or ligation/excision of branch aneurysms, as well as concomitant management of distal thromboembolism.
A data anomaly was observed that affected the uniformity and reproducibility of fluorescent signal across DNA microarrays. Results from experimental sets designed to identify potential causes (from ...microarray production to array scanning) indicated that the anomaly was linked to a batch process; further work allowed us to localize the effect to the posthybridization array stringency washes. Ozone levels were monitored and highly correlated with the batch effect. Controlled exposures of microarrays to ozone confirmed this factor as the root cause, and we present data that show susceptibility of a class of cyanine dyes (e.g., Cy5, Alexa 647) to ozone levels as low as 5-10 ppb for periods as short as 10-30 s. Other cyanine dyes (e.g., Cy3, Alexa 555) were not significantly affected until higher ozone levels (> 100 ppb). To address this environmental effect, laboratory ozone levels should be kept below 2 ppb (e.g., with filters in HVAC) to achieve high quality microarray data.
Point-of-care(POC) tests enable rapid results and are well established in medical practice.Recent advances in analytical techniques have led to a new generation of POC devices that will alter ...gastrointestinal diagnostic pathways.This review aims to identify current and newtechnologies for the POC diagnosis of gastrointestinal cancer.A structured search of the Embase and Medline databases was performed.Papers reporting diagnostic tests for gastrointestinal cancer available as a POC device or containing a description of feasibility for POC application were included.Studies recovered were heterogeneous and therefore results are presented as a narrative review.Six diagnostic methods were identified(fecal occult blood, fecal proteins, volatile organic compounds, pyruvate kinase isoenzyme type M2, tumour markers and DNA analysis).Fecal occult blood testing has a reported sensitivity of 66%-85% and specificity greater than 95%.The others are at a range of development and clinical application.POC devices have a proven role in the diagnosis of gastrointestinal cancer.Barriers to their implementation exist and the transition from experimental to clinical medicine is currently slow.New technologies demonstrate potential to provide accurate POC tests and an ability to diagnose gastrointestinal cancer at an early stage with improved clinical outcome and survival.
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