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.

Hip and other osteoporotic fractures increase the risk of subsequent fractures in nursing home residents.

UNLABELLED: Nursing home residents with a history of hip fractures or prior osteoporotic fractures were found to have an increased risk of another osteoporotic fracture over the ensuing two years when compared to nursing home residents with no fracture history. INTRODUCTION: Because of the high prevalence of osteoporosis and fall risk factors in nursing home residents, it is possible that the importance of previous fracture as a marker for subsequent fracture risk may be diminished. We tested whether a history of prior osteoporotic fractures would identify residents at increased risk of additional fractures after nursing home admission. METHODS: We identified all Medicare enrollees aged 50 and older who were in a nursing home in North Carolina in 2000 (n=30,655). We examined Medicare hospitalization claims to determine which enrollees had been hospitalized in the preceding 4 years for a hip fracture (n=7,257) or other fracture (n=663). We followed participants from nursing home entry until the end of 2002 using Medicare hospital claims to determine which participants were hospitalized with a subsequent fracture (n=3,381). RESULTS: Among residents with no recent fracture history, 6.8% had a hospital claim for a subsequent fracture, while 15.1% of those with a prior non-hip fracture and 23.9% of participants with a prior hip fracture sustained subsequent fractures. Multivariate proportional hazards models of time to fracture indicated that persons with prior hip fractures are at three times higher risk (HR=2.99, 95% CI: 2.78, 3.21) and those hospitalized with other non-hip fractures are at 1.8 times higher risk of subsequent fractures (HR=1.84, 95% CI: 1.50, 2.25). CONCLUSION: Nursing home residents hospitalized with a prior osteoporotic fracture are at increased risk of a fracture.

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.

Prevalence and predictors of osteoporosis treatment in nursing home residents with known osteoporosis or recent fracture.

SUMMARY: We studied nursing home residents with osteoporosis or recent fracture to determine the frequency and predictors of osteoporosis treatment. There was wide variation in performance, and both clinical and systems variables predicted use. This study shows that improvement in osteoporosis care is possible and important for many nursing homes. INTRODUCTION: We determined the prevalence and predictors of osteoporosis evaluation and treatment in high-risk nursing home residents. METHODS: We identified 67 nursing facilities in North Carolina and Arizona with > 10 residents with osteoporosis or recent hip fracture. Medical records (n=895) were abstracted for osteoporosis evaluation [dual-energy X-ray absorptiometry (DXA), vitamin D level, serum calcium), treatment (calcium, vitamin D, osteoporosis medication, hip protectors), clinical, and systems covariates. Data were analyzed at the facility level using mixed models to account for the complex nesting of residents within providers and nursing facilities. RESULTS: Calcium and vitamin D was prescribed for 69% of residents, bisphosphonates for 19%, calcitonin for 14%, other pharmacologic therapies for 6%, and hip protectors for 2%. Overall, 36% received any bone protection (medication or hip protectors), with wide variation among facilities (0-85%). Factors significantly associated with any bone protection included female gender [odds ratio (OR) 2.4, (1.5-3.7)] and nonurban/suburban location [1.5, (1.1-2.2)]. Residents with esophagitis, peptic ulcer disease (PUD), or dysphagia [0.6, (0.4-0.9)] and alcohol abuse [0.2, (0.0-0.9)] were less likely to receive treatment. CONCLUSIONS: There is substantial variation in the quality of osteoporosis treatment across nursing homes. Interventions that improve osteoporosis quality of care are needed.

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.

Temperature and field dependence of the order parameter in the antiferroquadrupolar phase of CeB6 from mu+ Knight shift measurements.

The Fermi contact hyperfine contribution to the Knight shift of positive muons, implanted at the interstitial 3d sites in CeB6, is found to exhibit the same temperature dependence below T(Q) in phase II as the quadrupolar order parameter determined from resonant and nonresonant x-ray scattering. Furthermore, the contact coupling parameter is shown to be anisotropic and field dependent. These unanticipated features are interpreted to arise from the RKKY induced conduction electron spin polarization, which depends on the orientation and expectation value of the ordered 4f quadrupole moments.

Field-induced magnetization distribution and antiferroquadrupolar order in CeB(6).

The anisotropic Knight shift of implanted positive muons (micro(+)) in CeB(6) has been studied between 2.2 and 200 K in a field of 0.6 T. The results imply that the field-induced magnetization distribution is not only found at the Ce sites but also in other regions of the unit cell (e.g., near or inside the B6 molecule, as proposed by Saitoh et al. [J. Phys. Soc. Jpn. Suppl. 71, 106-108 (2002)]). While above the antiferroquadrupolar ordering temperature T(Q) approximately 3.55 K this additional magnetization appears to be antiparallel to the Ce moments, a drastic change is observed below T(Q), and the additional magnetization is eventually aligned parallel to the Ce moments.

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.

A highly conserved protein family interacting with the fragile X mental retardation protein (FMRP) and displaying selective interactions with FMRP-related proteins FXR1P and FXR2P.

The absence of the fragile X mental retardation protein (FMRP), encoded by the FMR1 gene, is responsible for pathologic manifestations in the Fragile X Syndrome, the most frequent cause of inherited mental retardation. FMRP is an RNA-binding protein associated with polysomes as part of a messenger ribonucleoprotein (mRNP) complex. Although its function is poorly understood, various observations suggest a role in local protein translation at neuronal dendrites and in dendritic spine maturation. We present here the identification of CYFIP1/2 (Cytoplasmic FMRP Interacting Proteins) as FMRP interactors. CYFIP1/2 share 88% amino acid sequence identity and represent the two members in humans of a highly conserved protein family. Remarkably, whereas CYFIP2 also interacts with the FMRP-related proteins FXR1P/2P, CYFIP1 interacts exclusively with FMRP. FMRP--CYFIP interaction involves the domain of FMRP also mediating homo- and heteromerization, thus suggesting a competition between interaction among the FXR proteins and interaction with CYFIP. CYFIP1/2 are proteins of unknown function, but CYFIP1 has recently been shown to interact with the small GTPase Rac1, which is implicated in development and maintenance of neuronal structures. Consistent with FMRP and Rac1 localization in dendritic fine structures, CYFIP1/2 are present in synaptosomal extracts.

Identifying and characterizing one-time and never users of mammography screening services among medicare eligible women.

BACKGROUND: Despite eligibility for a screening mammogram once every 2 years from 1991 to 1997, only a small percentage of Medicare women utilized this benefit. We examined mammography use among 388,707 North Carolina Medicare women from 1994 to 1997 to identify characteristics of one-time and never users of mammography. METHODS: Data were obtained from North Carolina Medicare mammography claims and enrollment files from 1994 to 1997. Women ages 65+ as of 01/01/1994, continuously enrolled in Medicare from 1994 to 1997, and alive as of 12/31/1997 were included in the sample (n = 388,707). Mammogram use was categorized as never, once, or at least twice during 1994/1995 and 1996/1997. Women with at least one mammography claim during 1994/1995 and at least one mammography claim during 1996/1997 were called repeat users, women with one mammography claim during the 4 years were labeled one-time users, and women with zero mammography claims during the 4 years were termed never users. Multivariate logistic regression analyses were conducted to determine associations between characteristics and mammography frequency. RESULTS: Biennial mammography claims data rates were 35.3% in 1994/1995 and 41.8% in 1996/1997. Compared with all other users, one-time users (n = 108,899) were more likely to be ages 65-74 (vs 75-84 and 85+), live in an urban versus rural county, and be eligible for Medicare only versus Medicare and Medicaid. Never users (n = 184,545) were more likely to be ages 85+, be non-Caucasian, live in a rural county, and be eligible for both Medicare and Medicaid versus Medicare. CONCLUSIONS: These results demonstrate different demographic characteristics for one-time and never mammography users. This approach of using multiple years of claims data to segment the targeted population provides the opportunity to tailor interventions to subgroups.

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.

Using north carolina medicare data to assess excess prostate cancer mortality among african americans.

PURPOSE: To investigate the basis for the higher prostate cancer mortality rate for African American (AA) men, which is twice the rate for White men.METHODS: 221 AA and 979 White men with a primary diagnosis code of prostate cancer ("patients") in the North Carolina Medicare Hospitalization claims from 1997 were compared with 1,326 AA and 5,874 White men of the same age with no cancer hospitalizations ("beneficiaries") selected from the NC Medicare Enrollment files. Mortality rates were calculated as the cumulative percent of deaths using the hospital discharge date as day 1. AA and White age distributions were similar.RESULTS: Cumulative mortality percentages at 6, 12, and 18 months were, respectively, 4.5, 7.7, 10.9 for AA patients; 2.8, 6.5, 9.2 for White patients; 2.3, 3.8, 7.4 for AA beneficiaries; and 1.8, 3.1, 6.1 for White beneficiaries.CONCLUSIONS: AA prostate cancer patients had higher overall mortality than did White prostate cancer patients during the first year, but by 12-months the White-Black survival advantage for prostate cancer patients was similar in magnitude to the White-Black survival advantage among the non-cancer Medicare beneficiaries. AAs' higher prostate cancer mortality may derive from higher short-term case fatality rates, which may reflect differences in treatment and access to quality medical care, co-morbidities, and tumor characteristics such as stage and grade at diagnosis, and in part from the survival disadvantage for AA in the general population.

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.

Magnetic quantum critical point and superconductivity in UPt3 doped with Pd.

Transverse-field muon spin relaxation measurements have been carried out on the heavy-fermion superconductor UPt (3) doped with small amounts of Pd. We find that the critical Pd concentration for the emergence of the large-moment antiferromagnetic phase is approximately 0.6 at. %Pd. At the same Pd content, superconductivity is completely suppressed. The existence of a magnetic quantum critical point in the phase diagram, which coincides with the critical point for superconductivity, provides evidence for ferromagnetic spin-fluctuation mediated odd-parity superconductivity, which competes with antiferromagnetic order.

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.

A novel RNA-binding nuclear protein that interacts with the fragile X mental retardation (FMR1) protein.

Silenced expression of the FMR1 gene is responsible for the fragile X syndrome. The FMR1 gene codes for an RNA binding protein (FMRP), which can shuttle between the nucleus and the cytoplasm and is found associated to polysomes in the cytoplasm. By two-hybrid assay in yeast, we identified a novel protein interacting with FMRP: nuclear FMRP interacting protein (NUFIP). NUFIP mRNA expression is strikingly similar to that of the FMR1 gene in neurones of cortex, hippocampus and cerebellum. At the subcellular level, NUFIP colocalizes with nuclear isoforms of FMRP in a dot-like pattern. NUFIP presents a C2H2 zinc finger motif and a nuclear localization signal, but has no homology to known proteins and shows RNA binding activity in vitro. NUFIP does not interact with the FMRP homologues encoded by the FXR1 and FXR2 genes. Thus, these results indicate a specific nuclear role for FMRP.

[Prevention of postoperative nausea and vomiting after hysterectomy with oral dolasetron, intravenous dehydrobenzperidol or a combination of both substances]. / Prophylaxe von postoperativer Ubelkeit und Erbrechen nach Hysterektomie mit oralem Dolasetron, intravenösem Dehydrobenzperidol (DHB) oder einer Kombination beider Substanzen. Eine placebokontrollierte Untersuchung.

OBJECTIVE: PONV is a frequent postoperative complication. The aim of this study was to assess the efficacy of oral dolasetron in comparison to intravenous droperidol (DHB) and to a combination of both drugs for prophylaxis of PONV. METHODS: 80 patients (ASA I-III) were randomly allocated to one of four groups and received the following medication: group A: 50 mg dolasetron was given orally 45-60 minutes before anaesthesia was induced, group B: 2.5 mg i.v. DHB + placebo p.o. was administered while inducing anaesthesia (positive control group), group C: 50 mg dolasetron was given 45-60 minutes before anaesthesia was induced and 2.5 mg i.v. DHB was given while inducing anaesthesia, group D: placebo tablet was administered 45-60 minutes before anaesthesia was induced (negative control group). PONV was assessed using a 5-point score: 0 = no symptoms, 1 = nausea, 2 = retching, 3 = vomiting, 4 = multiple vomiting. Metoclopramid was given as antiemetic if a patient reached two or more score points. RESULTS: PONV scores were significantly lower in group A and C (p < 0.001) compared to the control group. Patients treated with DHB showed a significantly lower PONV score in comparison to the placebo treated patients (p < 0.05). Between the groups A, B and C we found no significantly different PONV scores. Postoperative consumption of metoclopramid was significantly lower in the groups A (2.4 +/- 5.2 mg) and C (1.0 +/- 3.1 mg) than in the placebo group (6.0 +/- 6.8 mg), whereas between group B (3.0 +/- 5.7 mg) and D we found no significant differences. CONCLUSIONS: Single dose of oral dolasetron and single dose of intravenous DHB reduced PONV effectively, in patients undergoing gynaecologic surgery. A combination of dolasetron and DHB has no better effect than a single dose of oral dolasetron. Contrary to DHB the application of dolasetron decreased the postoperative antiemetic requirement significantly.