Visual search and target detection during simulated driving in Parkinson's disease.

Patients with Parkinson's Disease (PD) often exhibit difficulties with visual search that may impede their ability to recognize landmarks and cars while driving. The main objective of this study was to investigate visual search performances of both billboards and cars in patients with PD using a driving simulator. A second objective was to examine the role of cognitive functions in performing the visual search task while driving. Nineteen patients with PD (age: 68 ±â€¯8yo, sex (Men/Women): 15/4) and 14 controls (age: 60 ±â€¯11yo, sex: 7/7) first performed a battery of cognitive tests. They then drove in a simulator and were instructed to follow a lead vehicle while searching for billboards with the letter A (stationary target) or red cars (moving target) among other distractors. Accuracy and response times of visual search were the main outcome variables. Standard deviation of lateral position (SDLP) was the secondary outcome. During driving, patients were less accurate in identifying the targets, particularly for the stationary billboards located in the outer periphery. Within the group of patients, significant correlations were found between several measures of cognitive tests and simulator-based visual search accuracy. By contrast, only the score on the MOCA test correlated significantly with visual search accuracy in controls. Findings suggest that patients with PD have impaired visual search for more eccentric stationary targets while driving a simulator, which is likely due to cognitive deficits. Difficulties identifying objects in the outer periphery may have implications for driving safety. Decreased functional field of view under increased cognitive load may have attributed to the difficulties identifying these landmarks. This may impact the ability to identify, anticipate, and respond to important information (e.g., pedestrians, navigation signs, landmarks), especially in complex driving situations (e.g. urban driving or intersections).Future studies should be conducted in a larger sample size to determine whether a visual search task on a driving simulator may predict on-road driving performances.

Effects of the spatial repellent metofluthrin on landing rates of outdoor biting anophelines in Cambodia, Southeast Asia.

The emergence of artemisinin-resistant malaria in Southeast Asia is a major problem. The fact that many people become infected with malaria when they are outside has prompted the development of 'spatial' rather than topical repellents. The respective effects of one or four slow-release emanators of metofluthrin, a pyrethroid, were tested in Pailin, Pursat and Koh Kong, Cambodia. Numbers of mosquitoes counted in outdoor landing catches when one or four emanators were suspended close to the collector were compared with control collections. In Pailin, the effects of emanators on catches in Furvela tent traps and Centers for Disease Control (CDC) light traps suspended underneath houses were also investigated. Rate ratios were used to determine differences. A total of 29 255 mosquitoes were collected over 2934 h of landing collections, 87 nights of tent trapping and 81 nights of light trap capture. In Pailin, landing rates were reduced by 48% by a single emanator and by 67% by four emanators (P < 0.001). Similar reductions were observed in the number of mosquitoes collected in tent traps and the number of anophelines only collected in light traps. Results were similar in Pursat, but, for unknown reasons, those in Koh Kong showed no difference between control and metofluthrin collections (P > 0.05). These findings suggest that although the product can produce a significant effect, it requires further improvement.

Direct manipulation of perceived angular declination affects perceived size and distance: a replication and extension of Wallach and O'Leary (1982).

In two experiments involving a total of 83 participants, the effect of vertical angular optical compression on the perceived distance and size of a target on the ground was investigated. Replicating an earlier report (Wallach & O'Leary, 1982), reducing the apparent angular declination below the horizon produced apparent object width increases (by 33 %), consistent with the perception of a greater ground distance to the object. A throwing task confirmed that perceived distance was indeed altered by about 33 %. The results are discussed in relation to cue recruitment and to recent evidence of systematic bias in the perception of angular declination.

Mobility, mood and site of care impact health related quality of life in Parkinson's disease.

OBJECTIVE: Examine the correlates of Health Related Quality of Life (HRQL) in a large cohort of Parkinson's disease (PD) patients from National Parkinson Foundation (NPF) Centers of Excellence (COEs). BACKGROUND: Improving outcomes for PD will depend upon uncovering disease features impacting HRQL to identify targets for intervention and variables for risk-adjustment models. Differences in HRQL outcomes between COEs could uncover modifiable aspects of care delivery. METHODS: This cross-sectional study examined the relative contribution of demographic, social, clinical and treatment features potentially related to HRQL, as measured by the PDQ-39, in 4601 consecutive subjects from 18 COEs. Stepwise linear regression was utilized to identify correlates of HRQL. RESULTS: The variability in the PDQ-39 summary index score correlated with H&Y stage (R(2) = 22%), Timed up and Go (TUG) (17%), disease duration (11%), comorbidities (8%), cognitive status (8%), antidepressant use (6%) and center at which a patient received care (5%). Stepwise regression reordered the importance of the variables, with the H&Y first and TUG and the center becoming equal and the second most important variables determining the PDQ-39 total score. All independent variables together accounted for 44% of the variability in HRQL. CONCLUSIONS: We confirmed many but not all HRQL associations found in smaller studies. A novel observation was that the site of care was an important contributor to HRQL, suggesting that comparison of outcomes and processes among centers may identify best practices.

Genetic mapping identifies a major locus spanning P450 clusters associated with pyrethroid resistance in kdr-free Anopheles arabiensis from Chad.

Prevention of malaria transmission throughout much of Africa is dependent on bednets that are impregnated with pyrethroid insecticides. Anopheles arabiensis is the major malaria vector in Chad and efforts to control this vector are threatened by the emergence of pyrethroid resistance. WHO bioassays revealed that An. arabiensis from Ndjamena is resistant to pyrethroids and dichlorodiphenyltrichloroethane (DDT) but fully susceptible to carbamates and organophosphates. No 1014F or 1014S kdr alleles were detected in this population. To determine the mechanisms that are responsible for resistance, genetic crosses were established between the Ndja strain and an insecticide susceptible population from Mozambique. Resistance was inherited as an autosomal trait and quantitative trait locus (QTL) mapping identified a single major locus on chromosome 2R, which explained 24.4% of the variance in resistance. This QTL is enriched in P450 genes including 25 cytochrome P450s in total. One of these, Cyp6p4 is 22-fold upregulated in the Ndja strain compared with the susceptible. Piperonyl butoxide (PBO) synergist and biochemical assays further support a role for P450s in conferring pyrethroid resistance in this population.

Risk factors for recurrence of ovarian borderline tumors.

OBJECTIVE: The objective of this study was to identify clinicopathologic features that are associated with an increased risk of recurrence for borderline ovarian tumors (BOT). METHODS: We performed a retrospective review of all patients treated for BOT at our institution from 1979 to 2008. Progression-free survival (PFS) was defined as the time of diagnosis to time of recurrence/death or last follow-up. The Kaplan-Meier method was used to calculate the PFS rate and the Wilcoxon-Gehan test was performed to identify prognostic factors. RESULTS: A total of 266 patients were identified. The median age was 43 years (range, 15-94 years). The majority of patients (68.4%) had FIGO stage I disease and serous histology (73.7%). Only 23 (8.6%) patients developed recurrent disease. The median PFS was 19 years and the median follow-up was 4 years. Abnormal baseline CA-125 (>35 U/ml), advanced stage, age at diagnosis, and invasive implants were associated with decreased PFS. Of the 196 patients with serous BOT, those with a micropapillary pattern had a 3-year PFS of 75.9% (95%CI, 55.6-87.8) compared with 94.3% (95% CI, 88.4-97.3) for patients without micropapillary pattern (P<0.001). CONCLUSION: Age at diagnosis, an elevated preoperative CA-125, invasive implants, and micropapillary histology were clinical factors associated with increased risk of recurrence in women with BOT. Including these clinicopathologic features will likely identify patients at higher risk for recurrence, for whom development of new treatment strategies would be appropriate.

Practice Parameter: treatment of nonmotor symptoms of Parkinson disease: report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: Nonmotor symptoms (sleep dysfunction, sensory symptoms, autonomic dysfunction, mood disorders, and cognitive abnormalities) in Parkinson disease (PD) are a major cause of morbidity, yet are often underrecognized. This evidence-based practice parameter evaluates treatment options for the nonmotor symptoms of PD. Articles pertaining to cognitive and mood dysfunction in PD, as well as treatment of sialorrhea with botulinum toxin, were previously reviewed as part of American Academy of Neurology practice parameters and were not included here. METHODS: A literature search of MEDLINE, EMBASE, and Science Citation Index was performed to identify clinical trials in patients with nonmotor symptoms of PD published between 1966 and August 2008. Articles were classified according to a 4-tiered level of evidence scheme and recommendations were based on the level of evidence. RESULTS AND RECOMMENDATIONS: Sildenafil citrate (50 mg) may be considered to treat erectile dysfunction in patients with Parkinson disease (PD) (Level C). Macrogol (polyethylene glycol) may be considered to treat constipation in patients with PD (Level C). The use of levodopa/carbidopa probably decreases the frequency of spontaneous nighttime leg movements, and should be considered to treat periodic limb movements of sleep in patients with PD (Level B). There is insufficient evidence to support or refute specific treatments for urinary incontinence, orthostatic hypotension, and anxiety (Level U). Future research should include concerted and interdisciplinary efforts toward finding treatments for nonmotor symptoms of PD.

Reduced susceptibility to DDT in field populations of Anopheles quadriannulatus and Anopheles arabiensis in Malawi: evidence for larval selection.

Bioassays for insecticide resistance in adult mosquitoes were conducted on samples of Anopheles gambiae Giles s.l. (Diptera: Culicidae) species collected as larvae from breeding sites in the lower Shire Valley, Malawi. The results indicate full susceptibility to permethrin, deltamethrin and malathion, but reduced susceptibility to DDT in one sample from Thom (LT(50) of 8.39 min for females and 25.09 min for males). Polymerase chain reaction-based species identification of the mosquitoes assayed revealed a mixture of Anopheles arabiensis Patton and Anopheles quadriannulatus (Theobold). The LT(50) did not differ significantly between species. Genotyping of the L1014F and L1014S kdr alleles showed all mosquito specimens to be homozygous wild type; thus the reduced susceptibility detected is not attributable to target site insensitivity and instead is likely to be metabolic in nature. Anopheles quadriannulatus is characteristically zoophagic and exophilic. Indeed, of 82 Anopheles collected through knockdown collections within dwellings, only one was An. quadriannulatus and the rest were An. arabiensis. They are unlikely, therefore, to have been exposed to selection pressure arising from insecticide-treated net usage or to DDT indoor residual spraying. Therefore, it is suggested that this example of reduced susceptibility to DDT in An. quadriannulatus reflects selection in the larval stages.

Overexpression of D2/D3 receptors increases efficacy of ropinirole in chronically 6-OHDA-lesioned Parkinsonian rats.

Ropinirole, which is a non-ergot dopamine agonist derivative, exerts therapeutic benefits in Parkinson's disease (PD). Based on recent studies implicating dopamine receptors 2 and 3 (D2R and D3R) as possible targets of ropinirole, we over-expressed these dopamine receptor genes in the dopamine-denervated striatum of rodents to reveal whether their over-expression modulated ropinirole activity. Adult Sprague-Dawley rats initially received unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. At 1 month after surgery, successfully lesioned animals (3 or less forelimb akinesia score, and 8 or more apomorphine-induced rotations/min over 1 h) were randomly assigned to intrastriatal injection (ipsilateral to the lesion) of blank lentiviral vector, D2R, D3R or both genes. At about 5 months post-lesion, ropinirole (0.2 mg/kg, i.p.) was administered daily for 9 consecutive days. The subtherapeutic dose of ropinirole improved the use of previously akinetic forelimb and produced robust circling behavior in lesioned animals with striatal over-expression of both D2R and D3R compared to lesioned animals that received blank vector. In contrast, the subtherapeutic dose of ropinirole generated only modest motor effects in lesioned animals with sole over-expression of D2R or D3R. Western immunoblot and autoradiographic assays showed enhanced D2R and D3R protein levels coupled with normalized D2R and D3R binding in the ventral striatum of lesioned animals with lentiviral over-expression of both D2R and D3R relative to vehicle-treated lesioned animals. Immunohistochemical analyses showed that D2R and D3R GFP fluorescent cells colocalized with enkephalin and substance P immunoreactive medium spiny neurons. These data support the use of the subtherapeutic dose of ropinirole in a chronic model of PD.

Botulinum toxin A during pregnancy: a survey of treating physicians.

Botulinum toxin A (btxA) is widely used for cosmetic purposes, headaches, dystonia, spasticity, pain and other on and off label uses. Despite the widespread use of btxA in women of childbearing potential, there are few data on the effects of this drug on pregnant women and the fetus. The goal of this study was to survey physicians who use btxA, to determine their experience with pregnant women. We surveyed 900 physicians who used commercially available btxA. The questionnaire asked treating physicians if they had knowingly or unknowingly injected pregnant women and what was the outcome of each pregnancy. In total, 396 physicians (44%) returned questionnaires, of whom only 12 physicians reported injecting pregnant women with btxA. Sixteen pregnant women were injected, mostly in the first trimester, and only one patient, who had prior spontaneous abortions, suffered a miscarriage. Another woman had a therapeutic abortion. All other pregnancies went to term and there were no fetal malformations. Based on this limited survey of treating physicians in the USA, btxA appears to be relatively safe for both expectant mother and fetus. We need further data, however, and we would recommend that physicians and patients carefully consider the risks and benefits before using btxA in pregnant women.

Characterization of a military training site containing 232Thorium.

Understanding contaminant distribution is critical to selection and implementation of effective and affordable containment and remediation efforts. This article describes the characterization of soil containing thorium at a training site on Kirtland Air Force Base, Albuquerque, NM. The site has been used by the Defense Nuclear Weapons School since the early 1960's to train personnel in emergency response to nuclear weapons accidents and for characterization and containment of radioactive contamination. The purpose of work reported herein is to describe the primary location and migration pattern of 232Thorium (232Th) and 232Th progeny (decay products) at the site. Soil containing thorium oxide (ThO2) was applied to the site for approximately 30 years (early 1960-1990) and was used to simulate a plutonium release from a nuclear weapons accident. Data presented indicate that surface 232Th and 232Th progeny at approximately 5 times background levels are approaching test site boundaries. However, the data also indicate that vertical migration has not exceeded 0.9 m because of the insoluble nature of ThO2. The major mechanisms of 232Th mobility appear to be surface migration mediated by precipitation runoff and wind-blown soil.

Reversible corpus callosum lesion in legionnaires' disease.

Legionnaires' disease is often associated with neurological findings. Despite such findings, computed tomography and neuropathological investigations are typically normal. This report describes a reversible lesion of the corpus callosum identified on magnetic resonance imaging (MRI) in a patient with legionnaires' disease. MRI may show previously undocumented neuropathology in acute legionnaires' disease. Legionella pneumophila infection should be included in the differential diagnosis of conditions associated with reversible lesions of the corpus callosum.

Pyrethroid and DDT cross-resistance in Aedes aegypti is correlated with novel mutations in the voltage-gated sodium channel gene.

Samples of the dengue vector mosquito Aedes aegypti (L.) (Diptera: Culicidae) were collected from 13 localities between 1995 and 1998. Two laboratory strains, Bora (French Polynesia) and AEAE, were both susceptible to DDT and permethrin; all other strains, except Larentuka (Indonesia) and Bouaké (Ivory Coast), contained individual fourth-instar larvae resistant to permethrin. Ten strains were subjected to a range of biochemical assays. Many strains had elevated carboxylesterase activity compared to the Bora strain; this was particularly high in the Indonesian strains Salatiga and Semarang, and in the Guyane strain (Cayenne). Monooxygenase levels were increased in the Salatiga and Paea (Polynesia) strains, and reduced in the two Thai strains (Mae Kaza, Mae Kud) and the Larentuka strain. Glutathione S-transferase activity was elevated in the Guyane strain. All other enzyme profiles were similar to the susceptible strain. The presence of both DDT and pyrethroid resistance in the Semarang, Belem (Brazil) and Long Hoa (Vietnam) strains suggested the presence of a knock-down resistant (kdr)-type resistance mechanism. Part of the S6 hydrophobic segment of domain II of the voltage-gated sodium channel gene was obtained by RT-PCR and sequenced from several insects from all 13 field strains. Four novel mutations were identified. Three strains contained identical amino acid substitutions at two positions, two strains shared a different substitution, and one strain was homozygous for a fourth alteration. The leucine to phenylalanine substitution that confers nerve insensitivity to pyrethroids in a range of other resistant insects was absent. Direct neurophysiological assays on individual larvae from three strains with these mutations demonstrated reduced nerve sensitivity to permethrin or lambda cyhalothrin inhibition compared to the susceptible strains.

Wild-type and mutant forms of v-src differentially alter neuronal migration and differentiation in vivo.

The effects of three different forms of v-src on brain cell development were determined in vivo. Recombinant retroviral vectors encoding the marker lacZ (control) and either wild-type v-src or SH2 or SH3 domain-deleted forms of v-src (deltaSH2 or deltaSH3, respectively) were used to infect neuronal progenitor cells in the embryonic chicken midbrain (optic tectum; OT). Embryos were injected in the OT with retroviral concentrates on embryonic day (E) 3 and sacrificed at E6, E9, and later in development. Patterns of cell proliferation, migration, and differentiation of lacZ-marked clonal cell progeny were then analyzed. Relative to lacZ-only controls, cell clone size at E6 was significantly increased for v-src-, unchanged for deltaSH2-, and smaller for deltaSH3-injected embryos. At E9, deltaSH2 cell clones were significantly larger than controls, suggesting increased survival from normal programmed cell death. Radial neuronal migration was impaired for v-src and deltaSH3 clones, whereas tangential neuronal migration was enhanced along fiber tracts in v-src and deltaSH2 clones. Moreover, radial glial cell development and differentiation was hindered in v-src and deltaSH3 clones. These experiments demonstrate that ectopic v-src signaling alters proliferation, migration, survival, and differentiation of developing brain cells and suggest that src signaling pathways are involved in these developmental processes. Furthermore, certain effects of v-src on brain cells require specific src homology domains.

Two mutations in the locus control region hypersensitivity site-2 (5' HS-2) of haplotype 19 beta s chromosomes alter binding of trans-acting factors.

There are five major haplotypes associated with sickle cell anemia (SS). Individuals homozygous for haplotypes 3 (Senegal) and 31 (Saudi Arabian) have high fetal hemoglobin (HbF) levels (15 to 30% of total hemoglobin) whereas individuals homozygous for haplotypes 17 (Cameroon), 19 (Benin), and 20 (Bantu) have low HbF levels (1 to 10%). We previously identified several point mutations in the LCR 5'HS-2 that were specific for haplotype 19 beta s chromosomes (compared to the GenBank HUMHBB reference sequence, T-->G at position 8580, A-->G at position 8598, and A-->T at position 9114). We postulated that one or more of these mutations may alter the binding of specific trans-acting factors and ultimately affect the expression of HbF in these sickle cell patients. We performed gel mobility shift assays using 32P-end-labeled double-stranded 19mers corresponding to each of the LCR 5'HS-2 normal (GenBank) and mutant sequences. Nuclear extracts prepared from HeLa and HEL cells were used in our experiments and neither the normal nor mutant sequence at position 8580 bound trans-acting factors in either nuclear extract. The 8598 mutant increased binding of Sp1; using purified protein and both nuclear extracts. HEL extracts were used to quantify the increase in Sp1 binding to the 8598 mutation and we found an increase in binding of 66 and 47%, respectively, in two shifted bands. The 9114 mutation sharply decreased binding of an unknown trans-acting factor by 74%. This factor was present in both HeLa and HEL nuclear extracts.

Students who work.

A study of 1,800 Kentucky high school students revealed that working students demonstrate a remarkable diversity of work experience and uses of earnings while not differing markedly from nonworking students in school experience. The data, both quantitative and qualitative, suggest that conventional wisdom is not sufficient to capture fully the current realities of students who work; however, unresolved theoretical issues remain.