ADHD-associated dopamine transporter, latrophilin and neurofibromin share a dopamine-related locomotor signature in Drosophila.

Attention-deficit/hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder with hyperactivity as one of the hallmarks. Aberrant dopamine signaling is thought to be a major theme in ADHD, but how this relates to the vast majority of ADHD candidate genes is illusive. Here we report a Drosophila dopamine-related locomotor endophenotype that is shared by pan-neuronal knockdown of orthologs of the ADHD-associated genes Dopamine transporter (DAT1) and Latrophilin (LPHN3), and of a gene causing a monogenic disorder with frequent ADHD comorbidity: Neurofibromin (NF1). The locomotor signature was not found in control models and could be ameliorated by methylphenidate, validating its relevance to symptoms of the disorder. The Drosophila ADHD endophenotype can be further exploited in high throughput to characterize the growing number of candidate genes. It represents an equally useful outcome measure for testing chemical compounds to define novel treatment options.

Do physicians within the same practice setting manage osteoporosis patients similarly? Implications for implementation research.

UNLABELLED: Using data from long-term glucocorticoid users and long-term care residents, we evaluated osteoporosis prescribing patterns related to physician behavior and common practice settings. We found no significant clustering effect for common practice setting, suggesting that osteoporosis quality improvement (QI) efforts may be able to ignore this factor in designing QI interventions. INTRODUCTION: Patients' receipt of prescription therapies are significantly influenced by their physician's prescribing patterns. If physicians in the same practice setting influence one another's prescribing, evidence implementation interventions must consider targeting the practice as well as individual physicians to achieve maximal success. METHODS: We examined receipt of osteoporosis treatment (OP Rx) from two prior evidence implementation studies: long-term glucocorticoid (GC) users and nursing home (NH) residents with prior fracture or osteoporosis. Common practice setting was defined as doctors practicing at the same address or in the same nursing home. Alternating logistic regression evaluated the relationship between OP Rx, common practice setting, and individual physician treatment patterns. RESULTS: Among 6,281 GC users in 1,296 practices, the proportion receiving OP Rx in each practice was 6-100%. Among 779 NH residents in 66 nursing homes, the proportion in each NH receiving OP Rx was 0-100%. In both, there was no significant relationship between receipt of OP Rx and common practice setting after accounting for treatment pattern of individual physicians. CONCLUSION: Physicians practicing together were not more alike in prescribing osteoporosis medications than those in different practices. Osteoporosis quality improvement may be able to ignore common practice settings and maximize statistical power by targeting individual physicians.

Spontaneous Magnetic Ordering in the Fullerene Charge-Transfer Salt (TDAE)C60.

The zero-field muon spin relaxation technique has been used in the direct observation of spontaneous magnetic order below a Curie temperature (T(c)) of approximately 16.1 kelvin in the fullerene charge-transfer salt (tetrakisdimethylaminoethylene)C(60) [(TDAE)C(60)]. Coherent ordering of the electronic magnetic moments leads to a local field of 68(1) gauss at the muon site at 3.2 kelvin (parentheses indicate the error in the last digit). Substantial spatially inhomogeneous effects are manifested in the distribution of the local fields, whose width amounts to 48(2) gauss at the same temperature. The temperature evolution of the internal magnetic field below the freezing temperature mirrors that of the saturation magnetization, closely following the behavior expected for collective spin wave (magnon) excitations. The transition to a ferromagnetic state with a T(c) higher than that of any other organic material is now authenticated.

Complex-shaped platinum coils for brain aneurysms: higher packing density, improved biomechanical stability, and midterm angiographic outcome.

BACKGROUND AND PURPOSE: Five to 60% of coiled brain aneurysms recanalize, generally because of coil compaction. In vitro exclusive use of complex-shaped coils allows better packing of the aneurysmal sac and the neck as compared with helical coils. We report a single-center, prospective study using complex coils. Safety, packing density, and recanalization rate were evaluated. MATERIALS AND METHODS: Seventy-seven aneurysms were embolized using complex coils alone. Aneurysms had a volume of 265 mm3 (diameter: 7.1+/-3.3 mm) and a neck size of 4.1+/-1.8 mm (range: 1.5-12 mm). Average follow-up available in 31 patients was 10.5+/-7.6 months (range: 3-36 months). Primary angiographic endpoints included aneurysmal recanalization and (re)rupture. Primary adverse events included stroke or death. RESULTS: Complete or near-complete occlusion was achieved in all of the aneurysms but required balloon assistance in 24.6%. The packing density was computed as 37%+/-13%. No rerupture was observed during the follow-up interval. Recanalization was seen in 4 (12.9%) of 31. Two basilar tip aneurysms underwent a safe and complete recoiling. Periprocedural nondevice-related neurologic deficits were seen in 2 (2.9%) of 69 patients. CONCLUSIONS: The use of complex-shaped coils allows higher packing density, which may improve the recanalization rate. Basilar tip aneurysms remain a challenge.

Anisotropic 4f-spin dynamics across the B-T phase diagram of Ce(7)Ni(3).

Longitudinal field µSR measurements in applied fields parallel and perpendicular to the c-axis of the hexagonal heavy-fermion antiferromagnet Ce(7)Ni(3) served to monitor the 4f-spin dynamics across the magnetic phase diagram in the B-T plane, which consists of an incommensurate/commensurate antiferromagnetic (AF) section below 1.9 K/0.7 K and below an applied field B of 0.25 T, and for B along the c-axis, of a field-induced magnetic (FIM) section for B≥0.6 T and below 0.5 K. The observed µ(+) spin-lattice relaxation rates reveal persisting spin dynamics across the whole phase diagram, reflect the various phase boundaries and are interpreted to arise in the AF and FIM phases from the Ce3 sublattice (the Ce ions are located on three different sublattices) and in the intermediate phase, viewed as a short range ordered (SRO) state, also from the Ce1 and Ce2 sublattices with slower fluctuation rates. In the paramagnetic regime the Ce1 sublattice displays the slowest spin dynamics. In the FIM phase the fraction of relaxing µ(+) appears to shrink with rising B, evidencing a possible phase separation.

Effect of angiotensin-converting enzyme inhibitor therapy on 30-day outcome in patient > or = 65 years of age with chronic congestive heart failure.

Patients discharged from the hospital on an angiotensin-converting enzyme inhibitor had a significant decrease in 30-day death or readmission (by 30% in 1,195 unselected Medicare patients hospitalized with congestive heart failure). Other independent predictors of poor outcome determined by multivariate analysis included history of congestive heart failure, male gender, increased number of comorbidities, higher serum blood urea nitrogen, and lower serum sodium.

Evidence for a two component magnetic response in UPt3

The magnetic response of the heavy fermion superconductor UPt3 has been investigated on a microscopic scale by muon Knight shift studies. Two distinct and isotropic Knight shifts have been found for the field in the basal plane. While the volume fractions associated with the two Knight shifts are approximately equal at low and high temperatures, they show a dramatic and opposite temperature dependence around T(N). Our results are independent on the precise muon localization site. We conclude that UPt3 is characterized by a two component magnetic response.

Relationship of DNA ploidy to hormone receptor status and proliferation in invasive breast carcinoma.

PURPOSE: In 247 primary invasive breast carcinomas, DNA ploidy was related to hormone receptor status, proliferation, and clinical/histopathologic factors. METHODS: DNA ploidy analysis was performed by image analysis using imprints. Estrogen (ER) and progesterone (PR) receptor status was determined immunohistochemically. The proliferative activity of the tumours was assessed by Ki-67 antigen labelling. Total observation time was 3.5 years. RESULTS: DNA ploidy analysis revealed a high fraction of tumours with non-peridiploid patterns (78%). Significant correlations between DNA ploidy and ER/PR receptor status (P < 0.01) were found with increased frequencies of peridiploid DNA results in receptor positive tumours. A significant relationship became manifest between DNA ploidy and Ki-67 index showing high frequencies of non-peridiploid DNA patterns in tumours with Ki-67 index > 20% (P < 0.01). There was a strong correlation (P < 0.001) between DNA ploidy and histopathologic grading, while tumour size and lymph node status were not correlated to DNA ploidy. CONCLUSIONS: The results of our study on invasive breast carcinoma demonstrate that DNA ploidy measured by image analysis is predominantly associated with markers of cell differentiation. Preliminary outcome data reveal a risk-indicating potential of DNA ploidy primarily in cases with favourable results for other prognostic factors.

The Fragile X mental retardation protein.

The clinical features of the Fragile X mental retardation syndrome are linked to the absence of the set of protein isoforms, derived from alternative splicing of the Fragile X mental retardation gene 1 (FMR1), and collectively termed FMRP. FMRP is an RNA binding protein that is part of a ribonucleoprotein particle associated to actively translating polyribosomes, and which can shuttle between nucleus and cytoplasm. Two highly homologous human proteins, FXR1P and FXR2P, share the same domain structure as FMRP, and probably similar functions. The properties of FMRP suggested that it is involved in nuclear export, cytoplasmic transport, and/or translational control of target mRNAs. In particular, it may play a role in regulation of protein synthesis at postsynaptic sites of dendrites, and in maturation of dendritic spines. Efforts are underway to identify the putative specific mRNA targets of FMRP, and study the effect of FMRP absence on the corresponding proteins. Other approaches have led to the identification of proteins that interact with FMRP. Some of them discriminate between FMRP and the homologous FXR1/2P proteins, and may thus be important for defining unique functions of FMRP that are deficient in Fragile X patients. The physiological functions of FMRP are notably approached through the study of a FMR1 knock-out mouse model. The recent identification in Drosophila melanogaster of genes encoding homologs of FMRP/FXRP and of their interacting proteins, open the way to use of Drosophila genetics to study FMRP function.

Previous cesarean birth. A risk factor for placenta previa?

OBJECTIVE: To study the risk of placenta previa following a previous cesarean birth. STUDY DESIGN: We conducted a population-based, case-control study using 1990 North Carolina state birth certificate data. The study population included 342 women with a pregnancy complicated by placenta previa and 1,082 randomly selected controls. Analysis was restricted to women who reported one or more previous live births and delivered a singleton, live neonate. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated using logistic regression, controlling for maternal age, race, prior spontaneous or induced abortions and cigarette use. RESULTS: When the data were adjusted for maternal age, race, prior spontaneous or induced abortions, and cigarette use, women who had a previous cesarean birth and had a parity of 3 were 1.7 times more likely (OR 1.7, 95% CI 0.7, 4.2) and women of parity > or = 4 were 5.5 times more likely (OR 5.5, 95% CI 1.0, 30.1) to have placenta previa than women of parity 1 who had a previous cesarean birth. CONCLUSION: Women with a history of a previous cesarean birth and parity > or = 3 were at increased risk of having a pregnancy complicated by placenta previa.