bluuebunny/crossref_metadata_2025 huggingface dataset:
Location of osteoclast precursors in fetal rat calvaria cultured on collagen gels
Authors: Braidman Isobel P. , Rothwell Claire , Webber David M. , Crowe Peter , Anderson David C.
Published: March 2010

Although osteoclasts are derived from hematopoietic cells, the exact identity of their precursors and the mechanism for their recruitment onto bone surfaces remain unclear. We wished to study their differentiation in the fetal rat calvaria and to locate its source of osteoclast precursor cells. Osteoclasts were detected by neutral red staining or cytochemical reaction for acid phosphatase of intact bone (cell number and area measured by computerized image analysis) or in cryostat sections of bone (enzyme activity measured by quantitative cytochemistry). Histology of semithin sections of fixed bones was also examined. The 19 day calvariae contained few mature osteoclasts. After 48 h culture on gels of type 1 collagen (1.5 mg/ml) supplemented with 5 mM calcium β-glycerophosphate, 10 mM proline, and 2 μg/ml ascorbic acid, numerous large osteoclasts were seen on their endocranial surfaces. In contrast, cell morphology and enzyme activity deteriorated in bones cultured in liquid medium. The cells that formed in vitro rapidly responded to calcitonin by contraction. Stripping of endocranial membranes from the calvariae prevented osteoclast formation in culture, but these cells were seen when “stripped” bones had been cocultured with their membranes for 48 h or with intact 16 day calvariae (well before the onset of osteogenesis). Few osteoclasts were found when an 0.22μm filter was inserted between the stripped calvaria and the endocranial membranes. We conclude that the endocranial membranes, which contain the meningeal blood vessels, are a major source of osteoclast precursors and that these cells are present in calvarial tissue even before the onset of osteogenesis.
Parathyroid hormone stimulates formation of inositol phosphates in a membrane preparation of canine renal cortical tubular cells
Authors: Coleman Daniel T. , Dr. Bilezikian John P.
Published: March 2010

Recent studies have shown that, in addition to its well-known action to stimulate adenylate cyclase activity, parathyroid hormone (PTH) may stimulate the inositol phosphate second messenger system in its target tissues, bone and kidney. We have developed a membrane preparation of canine renal cortex to test this hypothesis. We also have examined the potential role of guanine nucleotides on the formation of inositol phosphates (IPs) in this tissue. Collagenase-dispersed tubules were labeled with [3H]inositol, and membranes containing labeled phospholipase C (PLC) substrates ([3H]phosphatidyl inositol, [3H]phosphatidylinositol monophosphate, and [3H]phosphatidylinositol bisphosphate) were prepared. bPTH-(1–34) (100 nM) rapidly increased levels of all measured [3H]IPs (IP1, IP2, and IP3) 1.6–1.7-fold within the first 30 s of stimulation. The half-maximal concentration for the response to bPTH-(1–34) was approximately 8 nM. GTPγS (100 μM), a nonhydrolyzable analog of GTP, also increased levels of the three [3H]IPs (1.8 to 2.8-fold). The half-maximal concentration for the response to GTPγS was approximately 30 μM. In the presence of GTPμS, bPTH-(1–34) increased levels of IPs by up to 2.7 times more than GTPγS alone. The results indicate that bPTH-(1–34) can stimulate the formation of inositol phosphates in the kidney and suggest that PTH may activate a receptor coupled to this effect through a guanine nucleotide regulatory protein.
Opportunities and challenges of rural practice: managing self amid ambiguity
Authors: Curtin Lisa , Hargrove David S.
Published: March 2010

Living and practicing psychology in a small, rural community has opportunities and challenges. We describe the context of rural communities and identify several of those challenges and opportunities. A case study demonstrates the influence of multigenerational involvement, complex professional and social situations, and the potential difficulties facing the responsible clinician. We suggest both a theoretical perspective and specific procedures for treating prototypical cases in a rural practice. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 66:1–13, 2010.
Technology of creation of an expert system for diagnosing thyroid pathology based on a set of qualitative signs of cell atypia
Authors: Kirillov Vladimir , Gladyshev Alexander , Demidchik Evgeny
Published: March 2010

An expert system for differential diagnosis of thyroid pathology has been developed, in which the function of transforming qualitative signs of cell atypia into the quantitative form is realized. It based on the set of qualitative signs of cell atypia and works in the mode by the question—answer principle. An expert system (software) contained the X‐matrix and six standard S‐matrices. The X‐matrix was designed for filling with the alternative answers yes/no regarding the presence of cells with characteristic signs of atypia in the visual fields of a preparation. S‐matrices characterized the main forms of thyroid diseases, such as papillary and follicular cancer, follicular adenoma, autoimmune thyroiditis, nodular colloid and diffuse toxic goiter, by their set of yes/no answers. The answers entered to the X‐matrix were compared with answers of the S‐matrix. Each element of each S‐matrix, besides the answers yes/no, contained its weighting coefficient corresponding to a qualitative feature of a certain nosologic form. Weighting coefficient of each feature for every nosologic form was calculated by their frequency of occurrence in 30 visual fields. Comparison of X‐matrices with S‐matrices and verification of diagnosis according to the value of a diagnostic index with a percentage probability was performed in the automatic mode. Diagnostic index was determined by the sum of weighting coefficients of features with the coincident yes/no answers, while comparing X‐matrix elements with the corresponding S‐matrix elements. The software displayed on the monitor is the list of nosologic forms in the order of decreasing the diagnostic index values. Microsc. Res. Tech. 73:1091–1100, 2010. © 2010 Wiley‐Liss, Inc.
Near future ocean acidification increases growth rate of the lecithotrophic larvae and juveniles of the sea star Crossaster papposus
Authors: Dupont Sam , Lundve Bengt , Thorndyke Mike
Published: March 2010

Ocean acidification (OA) is believed to be a major threat for near‐future marine ecosystems, and that the most sensitive organisms will be calcifying organisms and the free‐living larval stages produced by most benthic marine species. In this respect, echinoderms are one of the taxa most at risk. Earlier research on the impact of near‐future OA on echinoderm larval stages showed negative effects, such as a decreased growth rate, increased mortality, and developmental abnormalities. However, all the long‐term studies were performed on planktotrophic larvae while alternative life‐history strategies, such as nonfeeding lecithotrophy, were largely ignored. Here, we show that lecithotrophic echinoderm larvae and juveniles are positively impacted by ocean acidification. When cultured at low pH, larvae and juveniles of the sea star Crossaster papposus grow faster with no visible affects on survival or skeletogenesis. This suggests that in future oceans, lecithotrophic species may be better adapted to deal with the threat of OA compared with planktotrophic ones with potentially important consequences at the ecosystem level. For example, an increase in populations of the top predator C. papposus will likely have huge consequences for community structure. Our results also highlight the importance of taking varying life‐history strategies into account when assessing the impacts of climate change, an approach that also provides insight into understanding the evolution of life‐history strategies. J. Exp. Zool. (Mol. Dev. Evol.) 314B:382–389, 2010. © 2010 Wiley‐Liss, Inc.
Stratification and synaptogenesis in the mushroom body of the honeybee, Apis mellifera
Authors: Ganeshina Olga
Published: March 2010

Stratification is a basic anatomical feature of central brain in both vertebrates and many invertebrates. The aim of this study was to investigate the relationship between stratification and synaptogenesis in the developing mushroom bodies of the honeybee. During metamorphosis, the vertical lobe of mushroom body shows progressive stratification with three thick primary strata and more secondary strata and laminae. Three primary strata are formed at the metamorphic stage P1, before the youngest generation of the mushroom body intrinsic neurons, Kenyon cells, is produced. Thus, the primary strata within the lobe are unlikely to represent three major subpopulations of the Kenyon cells sequentially produced in the mushroom bodies. Formation of laminae starts at the stage P2 and culminates at the end of metamorphosis. The laminae appear within the lobe rather than being added sequentially from the ingrowth stratum. Alternating dark and light lamina (lamina doublets) are formed in the vertical lobe in late metamorphosis (stages P6–P9), but they are not visible in adults. The pattern of stratification is not continuous along the vertical lobe at the same developmental stage, and resorting of axons of the Kenyon cells is likely to occur within dark laminae. In the developing vertical lobe, dark laminae show lower synaptic density and exhibit an ultra structure that is indicative for a delay in synaptogenesis relative to the primary strata. A local transient block of synaptogenesis within the dark laminae may provide correct targeting of Kenyon cells by extrinsic mushroom body neurons. J. Morphol., 2010. © 2010 Wiley‐Liss, Inc.
Intraarticular gene transfer of thrombospondin‐1 suppresses the disease progression of experimental osteoarthritis
Authors: Hsieh Jeng‐Long , Shen Po‐Chuan , Shiau Ai‐Li , Jou I‐Ming , Lee Che‐Hsin , Wang Chrong‐Reen , Teo Min‐Li , Wu Chao‐Liang
Published: March 2010

In osteoarthritis, angiogenesis, which occurs in the osteochondral junction and synovium, may accelerate inflammation and contribute to the severity of the disease. We used anterior cruciate ligament‐transection (ACLT) to investigate the therapeutic effect of an angiogenesis inhibitor, thrombospondin‐1 (TSP‐1), in a rat model of osteoarthritis. Osteoarthritis was induced in Wistar rats in the knee of one hind leg. After ACLT, AdTSP‐1 (adenoviral vector encoding mouse TSP‐1) was intraarticularly injected into the knee joints. Transgene expression, angiogenesis, and inflammatory responses in the knee joints were examined. They were also assessed morphologically, radiographically, and histologically for manifestations of disease. The levels of TSP‐1 peaked on day 3 and were substantially maintained for at least 9 days after AdTSP‐1 infection. Adenovirus‐mediated gene expression was detected in the synovial membrane and chondrocytes. TSP‐1 gene transfer induced transforming growth factor‐β (TGF‐β) production, but it reduced microvessel density, macrophage infiltration, and interleukin‐1β (IL‐1β) levels. Gross morphological and histopathological examinations revealed that rats treated with AdTSP‐1 had less severe osteoarthritis than controls. In vivo adenovirus‐mediated TSP‐1 gene transfer significantly reduced microvessel density, inflammation, and suppressed the progression of osteoarthritis. This study provides potential applications of TSP‐1 gene delivery for treating osteoarthritis. Published by Wiley Periodicals, Inc. J Orthop Res 28:1300–1306, 2010
Precise landmarking in computer assisted total knee arthroplasty is critical to final alignment
Authors: Brin Yaron S. , Livshetz Isaac , Antoniou John , Greenberg‐Dotan Sari , Zukor David J.
Published: March 2010

Image‐free computer navigation systems build a frame of reference of a patient's knee from anatomical landmarks entered by the surgeon during the initial stage of total knee arthroplasty. We performed tibial cuts on 70 sawbones using computer navigation. All landmarks were marked identically except for the tibial mechanical entry point, which was marked correctly in 10 bones and with offsets of 5, 10, and 15 mm medially and laterally in the others. The actual coronal angle of the tibial cuts was measured directly and compared to the final angle given by the navigation system. Significant deviations of the coronal angle were observed in the trial groups. Landmarking errors during navigated TKA can lead to inaccurate tibial bone cuts. This navigation system did not have an iterative software method to verify landmarking errors that can lead to inaccurate tibia bone cuts. Published by Wiley Periodicals, Inc. J Orthop Res 28:1355–1359, 2010
Effect of varying osmotic conditions on the response of bovine nucleus pulposus cells to growth factors and the activation of the ERK and Akt pathways
Authors: Mavrogonatou Eleni , Kletsas Dimitris
Published: March 2010

Intervertebral disc and especially nucleus pulposus is characterized by low cellularity. Additionally, extreme variations in osmolality are observed in this tissue, as a result of its specific physicochemical environment, daily activities, or degeneration. In this study, we investigated the role of osmotic fluctuations in the proliferative response of nucleus pulposus cells to exogenous growth factors. In particular, we examined the effect of platelet‐derived growth factor (PDGF) and insulin‐like growth factor‐I (IGF‐I) on the proliferation of bovine nucleus pulposus cells and on the activation of the MEK/ERK and PI‐3‐K/Akt pathways under varying osmotic conditions, in an effort to understand the mechanisms regulating cell proliferation in the intact and the degenerated intervertebral disc. Exposure of cells to high osmolality restrained novel DNA synthesis induced by PDGF or IGF‐I in a dose‐dependent manner and reduced ERK and Akt activation stimulated by serum or isolated growth factors. Our findings indicate that hyperosmolality imposes a strict control in intervertebral disc cells' proliferation, while hypo‐osmotic conditions prevailing in degenerated discs may offer a more permissive environment for cellular proliferation. Published by Wiley Periodicals, Inc. J Orthop Res 28:1276–1282, 2010
Evaluation of bone tunnel placement for suture augmentation of an injured anterior cruciate ligament: Effects on joint stability in a goat model
Authors: Fisher Matthew B. , Jung Ho‐Joong , McMahon Patrick J. , Woo Savio L‐Y.
Published: March 2010

Use of novel tissue engineering approaches to heal an injured anterior cruciate ligament (ACL) requires suture repair and/or augmentation to provide joint stability. We evaluated the effects of the location of suture augmentation at the femur and tibia in terms of joint stability using a goat model. Eight goat stifle joints were tested with augmentation sutures placed in two femoral tunnel locations: (1) anterior to, or (2) through the ACL footprint, and two tibial tunnel locations: (1) medial to, or (2) medial and lateral to the footprint. Using a robotic/universal force‐moment sensor testing system, the anterior tibial translation (ATT) and the corresponding in situ force carried by the sutures were obtained at 30°, 60°, and 90° of flexion in response to external loads. No significant differences were found between augmentation groups due to tunnel location in terms of ATT or the in situ forces carried by the sutures at all flexion angles tested. Similar results were found under 5 N m of varus–valgus torque. Under a 67 N anterior tibial load, the ATT was restored to within 3 mm of the intact joint following suture augmentation (p > 0.05). Suture augmentation, when placed close to the ACL insertion, could be helpful in providing initial joint stability to aid ACL healing in the goat model. Published by Wiley Periodicals, Inc. J Orthop Res 28:1373–1379, 2010
Antimicrobial and antioxidant activities of the essential oil from Herba Moslae
Authors: Li Jing‐en , Nie Shao‐ping , Qiu Zeng‐hui , Che Mei‐jing , Li Chang , Xie Ming‐yong
Published: March 2010

BACKGROUND: Herba Moslae is a well‐known edible and medicinal plant in China, and the essential oil, which is assumed to contain the active components, was isolated by steam distillation method. The aim of this study was to investigate the antimicrobial activity and the antioxidant activity of the essential oil from Herba Moslae.

RESULTS: The essential oil from Herba Moslae exhibited antimicrobial activity against all of the tested bacteria and fungi. The minimum inhibitory concentration (MIC) values for bacteria ranged from 118 to 472 µg mL−1, and the minimum bactericidal concentration (MBC) values were from 236 to 944 µg mL−1. The oil showed pronounced antibacterial and antifungal activity against Staphylococcus aureus and Aspergillus oryzae, but weak inhibition to Escherichia coli. The antioxidant activity of the essential oil from Herba Moslae was evaluated by using DPPH radical scavenging assay, β‐carotene/linoleic acid bleaching assay and metal chelating activity assay. In addition, the amount of total phenolic content in the oil (386 ± 1 µg kg−1) was determined.

CONCLUSION: This study suggests that the essential oil from Herba Moslae could be potentially used as a new potential source of natural antimicrobial, antioxidants and antiputrefactive in food industry. Copyright © 2010 Society of Chemical Industry
Optimum extraction process of polyphenols from Bridelia grandis stem bark using experimental design
Authors: Brusotti Gloria , Ngueyem Tatiana Adrienne , Biesuz Raffaela , Caccialanza Gabriele
Published: March 2010

Euphorbiaceae barks are known to contain an appreciable amount of polyphenolic compounds responsible for several biological activities. Preliminary extraction from Bridelia grandis stem bark afforded high content of polyphenols, determined by spectrophotometric methods such as Folin–Ciocalteu (for total phenols, TP) and n‐butanol‐HCl (for condensed tannins, CT). A preliminary Plackett–Burman screening design was used to identify the key factors that influence the TP and CT extraction. Between all the variables known to influence the extraction from vegetable matrixes, six were selected; maceration was chosen as traditional extraction methodology. To investigate the effect of solvents and extraction method, methanol, acetone 70% (v/v in water), centrifugation and ultrasound were chosen. A full factorial design 23 was applied to optimize the extraction procedure. The responses were obtained analyzing the extracts for their TP and CT contents determined by the above‐mentioned spectrophotometric methods. The results confirm that, within the explored domain, the optimum solvent is methanol and the optimum method is one‐cycle centrifugation. Finally, it was also compared with the effect of maceration on the considered responses. It has never given results better than centrifugation, whereas in the case of CT it represents an advantage to employ a three‐cycle centrifugation instead of one.
Fish oil: production and use now and in the future
Authors: Pike Ian H. , Jackson Andrew
Published: March 2010

The global production of fish oil is around one million tonnes. This production is expected to be maintained. Rich in long‐chain omega‐3 fatty acids, especially EPA and DHA, it can supplement diets inadequate in these fatty acids such as those in many Western countries. Farmed fish, especially oily fish such as salmonids fed on fish oil provide an excellent source of these acids. Fish oil can be used directly in a purified form (nutraceuticals) in a wide range of foods. The daily recommended intake of EPA plus DHA of 0.25 to 0.50 g can then be met.
How good is the evidence for a favourable effect of very long chain n‐3 polyunsaturated fatty acids on cardiovascular disease?
Authors: Stanley John
Published: March 2010

The evidence for beneficial effects of very long chain (VLC) n‐3 polyunsaturated fatty acids (PUFA) on cardiovascular disease (CVD) is strong because it is based on the results of adequately powered intervention trials with disease endpoints. This contrasts with the evidence for a detrimental effect of saturated fat on CVD which is weak because such studies have not been carried out. Accordingly, any set of dietary recommendations which attaches more importance to saturated fat intakes than VLC n‐3 PUFA intakes can be questioned. Despite the strength of the evidence there are practical difficulties associated with implementing the recommendation to increase intake of VLC n‐3 PUFA to 1g per day which need to be overcome. These include the acceptability of fatty fish consumption, the presence of methyl mercury in fish at the top of the food chain and declining global fish stocks.
Mental rotation of body parts and sensory temporal discrimination in fixed dystonia
Authors: Katschnig Petra , Edwards Mark J. , Schwingenschuh Petra , Aguirregomozcorta Maria , Kägi Georg , Rothwell John C. , Bhatia Kailash P.
Published: March 2010

Fixed dystonia is an uncommon but severely disabling condition typically affecting young women following a minor peripheral injury. There is no evidence of any structural lesions of the central nervous system nor any clear peripheral nerve or root damage. Electrophysiological techniques such as short intracortical inhibition, cortical silent period and a plasticity inducing protocol have revealed similarities but also differences compared to classical mobile dystonia. To further explore the pathophysiology of fixed dystonia we compared mental rotation of body parts and sensory temporal discrimination in 11 patients with fixed dystonia, 11 patients with classical mobile dystonia and 10 healthy controls. In the mental rotation task subjects were presented with realistic photos of left or right hands, feet and the head of a young women with a black patch covering the left or the right eye in six different orientations. Subjects had to verbally report the laterality of the presented stimuli. To assess sensory temporal discrimination subjects were asked to discriminate whether pairs of visual, tactile (electrical), or visuo‐tactile stimuli were simultaneous or sequential (temporal discrimination threshold) and in the latter case which stimulus preceded the other (temporal order judgement). In accordance with previous studies patients with mobile dystonia were abnormal in mental rotation and temporal discrimination, whereas patients with fixed dystonia were only impaired in mental rotation. Possible explanations for this deficit may include the influence of the abnormal body posture itself, a shared predisposing pathophysiology for mobile and fixed dystonia, or a body image disturbance. These findings add information to the developing pathophysiological picture of fixed dystonia. © 2010 Movement Disorder Society
Neurochemical alterations in spinocerebellar ataxia type 1 and their correlations with clinical status
Authors: Öz Gülin , Hutter Diane , Tkáč Ivan , Clark H. Brent , Gross Myron D. , Jiang Hong , Eberly Lynn E. , Bushara Khalaf O. , Gomez Christopher M.
Published: March 2010

Robust biomarkers of neurodegeneration are critical for testing of neuroprotective therapies. The clinical applicability of such biomarkers requires sufficient sensitivity to detect disease in individuals. Here we tested the sensitivity of high field (4 tesla) proton magnetic resonance spectroscopy (1H MRS) to neurochemical alterations in the cerebellum and brainstem in spinocerebellar ataxia type 1 (SCA1). We measured neurochemical profiles that consisted of 10 to 15 metabolite concentrations in the vermis, cerebellar hemispheres and pons of patients with SCA1 (N = 9) and healthy controls (N = 15). Total NAA (N‐acetylaspartate + N‐acetylaspartylglutamate, tNAA) and glutamate were lower and glutamine, myo‐inositol and total creatine (creatine + phosphocreatine, tCr) were higher in patients relative to controls, consistent with neuronal dysfunction/loss, gliotic activity, and alterations in glutamate–glutamine cycling and energy metabolism. Changes in tNAA, tCr, myo‐inositol, and glutamate levels were discernible in individual spectra and the tNAA/myo‐inositol ratio in the cerebellar hemipheres and pons differentiated the patients from controls with 100% specificity and sensitivity. In addition, tNAA, myo‐inositol, and glutamate levels in the cerebellar hemispheres and the tNAA and myo‐inositol levels in the pons correlated with ataxia scores (Scale for the Assessment and Rating of Ataxia, SARA). Two other biomarkers measured in the cerebrospinal fluid (CSF) of a subset of the volunteers (F2‐isoprostanes asa marker of oxidative stress and glial fibrillary acidic protein (GFAP) as a marker of gliosis) were not different between patients and controls. These data demonstrate that 1H MRS biomarkers can be utilized to noninvasively assess neuronal and glial status in individual ataxia patients. © 2010 Movement Disorder Society
Age of Parkinson's disease onset as a predictor for the development of dyskinesia
Authors: Ku Stephen , Glass Graham A.
Published: March 2010

The risk of developing levodopa‐associated dyskinesia is known to vary inversely with the age of Parkinson's disease onset. This study quantifies dyskinesia risks for different Parkinson's onset ages in a patient population treated at the Parkinson's Disease Research, Education, and Clinical Center at the San Francisco Veterans Affairs Medical Center. Medical records were reviewed to determine age of Parkinson's onset, medication history, and dyskinesia onset. Dyskinesia risks were determined by using Kaplan‐Meier analysis. Cox proportional hazard models were used to compare age groups and to perform multivariate modeling. This study included 109 patients with Parkinson's, 105 of whom had onset of symptoms after 1989. At 5 years of levodopa treatment, the dyskinesia risk for patients with onset age 40–49 was 70%, decreasing to 42% for onset ages 50–59, 33% for onset ages 60–69, and 24% for onset ages 70–79. Pairwise comparisons between the 40–49 age group and the other age groups were statistically significant in time‐to‐event models. After 5 years of levodopa treatment, dyskinesia risks became uniformly high regardless of age of onset. These results suggest it is appropriate to use different baseline dyskinesia risks in clinical decision‐making for patients on the basis of their ages of onset. However, the most significant difference occurs between ages 40–49 and ages 50–79, and if more than 5 years of levodopa therapy are anticipated, dyskinesia risk may have less utility when deciding upon Parkinson's therapy. Drug studies for Parkinson's disease should also take age of Parkinson's onset into account when analyzing dyskinesia outcomes. © 2010 Movement Disorder Society
Effect of histamine H2 receptor antagonism on levodopa–induced dyskinesia in the MPTP‐macaque model of Parkinson's disease
Authors: Johnston Tom H. , van der Meij Anne , Brotchie Jonathan M. , Fox Susan H.
Published: March 2010

Levodopa‐induced motor complications, including dyskinesia and wearing off, are troublesome side effects of treatment and impair quality of life in Parkinson's disease (PD) patients. The use of nondopaminergic agents as adjuncts to levodopa are potential options for managing these problems. Here, we asses the ability of the clinically available, selective histamine H2 antagonist, famotidine (1, 3, and 30 mg/kg) to treat levodopa‐induced dyskinesia and wearing off in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐macaque model of PD. Famotidine (3 mg/kg) increased peak activity, enhanced peak anti‐parkinsonian action (1 and 3 mg/kg), and extended duration of action (3 mg/kg, by 38%) of a low dose of levodopa (compared to low dose levodopa alone). Enhancement of anti‐parkinsonian actions of low dose levodopa by famotidine (3 mg/kg) was associated with only mild, nondisabling dystonia. Famotidine had no effect on the anti‐parkinsonian actions of high dose levodopa (compared to high dose levodopa alone). However, famotidine (1, 3, and 30 mg/kg) had a significant effect on chorea, but not dystonia, induced by high dose levodopa (compared to high dose levodopa alone). Famotidine increased high dose levodopa–induced “good quality” on time, i.e., on time not associated with disabling dyskinesia, by up to 28% (compared to high dose levodopa alone). In conclusion, famotidine, a drug currently available for use in the clinic, can enhance the peak‐dose anti‐parkinsonian actions and extend total duration of action of a low dose of levodopa, without producing disabling dyskinesia. Furthermore, in combination with a higher dose of levodopa, famotidine can reduce peak‐dose levodopa‐induced chorea and improve the quality of on‐time. © 2010 Movement Disorder Society
Task force report on scales to assess dyskinesia in Parkinson's disease: Critique and recommendations
Authors: Colosimo Carlo , Martínez‐Martín Pablo , Fabbrini Giovanni , Hauser Robert A. , Merello Marcelo , Miyasaki Janis , Poewe Werner , Sampaio Cristina , Rascol Olivier , Stebbins Glenn T. , Schrag Anette , Goetz Christopher G.
Published: March 2010

Drug‐induced dyskinesia is a common phenomenon in Parkinson's disease (PD) and is often socially as well as physically disabling for patients. The Movement Disorders Society commissioned a task force to assess available clinical rating scales, critique their clinimetric properties, and make recommendations regarding their clinical utility. A task force composed six clinical researchers who systematically searched the literature for scales measuring dyskinesia in PD, evaluated the scales' previous use, performance parameters, and quality of validation data (if available). A scale was designated “Recommended” if the scale has been used in clinical studies beyond the group that developed it, has been specifically used in PD reports, and if clinimetric studies have established that it is a valid, reliable, and sensitive. “Suggested” scales met two of the above criteria and those meeting one were “Listed.” Based on the systematic review, eight rating scales for dyskinesia that have either been validated or used in PD were identified. These were the Abnormal Involuntary Movement Scale (AIMS), The Unified Parkinson's Disease Rating Scale (UPDRS) part IV, the Obeso Dyskinesia Rating Scale, the Rush Dyskinesia Rating Scale, the Clinical Dyskinesia Rating Scale (CDRS), the Lang‐Fahn Activities of Daily Living Dyskinesia Scale, the Parkinson Disease Dyskinesia Scale (PDYS‐26), and the Unified Dyskinesia Rating Scale (UDysRS). Based on this review, at present two of the reviewed dyskinesia scales (AIMS and the Rush Dyskinesia Rating Scale) fulfill criteria for Recommended for use in PD populations, albeit weakly so; all of the remaining met criteria to be Suggested. However, the two most recent scales (PDYS‐26 and UDysRS) have excellent clinimetric properties and appear to provide a reliable and valid assessment tool of dyskinesia in PD. If they are used successfully beyond the groups that developed them, both have the potential to be re‐ranked as Recommended. As further testing of these scales in PD is warranted, no new scales are needed until the available scales are fully tested clinimetrically. © 2010 Movement Disorder Society
Association between cognition and function in patients with Parkinson disease with and without dementia
Authors: Rosenthal Emily , Brennan Laura , Xie Sharon , Hurtig Howard , Milber Joshua , Weintraub Daniel , Karlawish Jason , Siderowf Andrew
Published: March 2010

Patients with Parkinson's disease (PD) often have cognitive deficits from the time of diagnosis. Except in patients with dementia, the impact of cognitive symptoms on daily function is not well documented. This study had two objectives: (1) to determine the functional significance of cognitive deficits in nondemented patients with PD and (2) to assess the sensitivity of two measures of global cognitive abilities to identify individuals with impaired ADL function. One hundred eleven subjects with PD and a range of cognitive abilities were included. Of these, 20 were diagnosed with PDD. All subjects were assessed with the Mattis Dementia Rating Scale to two (DRS‐2) and the Mini‐Mental State Examination (MMSE). ADL function was reported by an informant using the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS‐ADL). The ability of the DRS‐2 and MMSE to capture the impact of cognitive impairment on ADL function was assessed in the entire cohort and in subsets of nondemented individuals. After adjustment for covariates, cognition as measured by the DRS‐2 was strongly related to ADL function in the entire cohort (partial correlation coefficient = 0.55, P < 0.001). The association remained strong when only nondemented subjects were included (r = 0.42, P < 0.001). The DRS‐2 was significantly more accurate than the MMSE, particularly for detecting milder degrees of ADL impairment (ROC area = 0.87 vs. 0.75, P = 0.0008). Cognition is associated with impairment in ADL function, even in nondemented patients with PD. However, sensitive cognitive assessment measures may be needed to identify these functionally relevant impairments. © 2010 Movement Disorder Society
Depression and the subsequent risk of Parkinson's disease in the NIH‐AARP Diet and Health Study
Authors: Fang Fang , Xu Qun , Park Yikyung , Huang Xuemei , Hollenbeck Albert , Blair Aaron , Schatzkin Arthur , Kamel Freya , Chen Honglei
Published: March 2010

We conducted a case‐control study to examine the association between depression and Parkinson's disease (PD). Participants included 992 PD cases diagnosed after 2,000 and 279,958 individuals without PD from the NIH‐AARP Diet and Health Study follow‐up survey. Physician‐diagnosed depression and PD were self‐reported with information on the year of diagnosis in the following categories: before 1985, 1985–1994, 1995–1999, and 2000–present. Only PD cases diagnosed after 2000 were included in the analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived from logistic regression models, adjusted for age, gender, educational level, marital status, smoking, and coffee drinking. Individuals with depression diagnosed after 2000 were more likely to report a concurrent diagnosis of PD than those without depression (OR = 4.7, 95% CI = 3.9, 5.7). Depression diagnosed before 2000 was also associated with higher odds of PD diagnosed after 2000 (OR = 2.0, 95% CI = 1.6, 2.4). This association was stronger for depression diagnosed in 1995–1999 (OR = 2.7, 95% CI = 2.0, 3.6), but was also noted for depression diagnosed in 1985–1994 (OR = 1.6, 95% CI = 1.1, 2.3) or even before 1985 (OR = 1.7, 95% CI = 1.3, 2.3). This association was not modified by other factors and persisted in an analysis excluding participants who reported poor health status. The results suggest that depression may either be a very early symptom of PD or share common etiological factors with PD. © 2010 Movement Disorder Society
Bladder symptoms assessed with overactive bladder questionnaire in Parkinson's disease
Authors: Iacovelli Elisa , Gilio Francesca , Meco Giuseppe , Fattapposta Francesco , Vanacore Nicola , Brusa Livia , Giacomelli Elena , Gabriele Maria , Rubino Alfonso , Locuratolo Nicoletta , Iani Cesare , Pichiorri Floriana , Colosimo Carlo , Carbone Antonio , Palleschi Giovanni , Inghilleri Maurizio
Published: March 2010

In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB‐q) is a measure designed to assess the impact of OAB symptoms on health‐related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB‐q short form. Possible correlations between the OAB‐q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB‐q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS‐III), Hoehn‐Yahr (H‐Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age‐matched healthy subjects. The OAB‐q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB‐q scores, UPDRS‐III scores, and H‐Y staging. A multiple linear regression analysis showed that OAB‐q values were significantly influenced by age and UPDRS‐III. No statistical correlations were found between OAB‐q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB‐q mainly correlates with UPDRS‐III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB‐q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD. © 2010 Movement Disorder Society
Changes in occurrences of temperature extremes in continental Portugal: a stochastic approach
Authors: Lucio P. S. , Silva A. M. , Serrano A. I.
Published: March 2010

In this paper the tail regions of the air‐surface temperature are modelled explicitly, using the recent developments of extreme value theory. The tails are estimated by fitting a Generalized Pareto Distribution to the observations disregarding certain thresholds (lying beyond) that mark the beginning of the tail regions. There are different approaches to characterize the spatial behaviour of climatological phenomena, and a particularly elegant formulation is derived from the theory of point process governing peaks‐over‐threshold. The aim of this study is to verify whether extreme values related to weather attributes from Continental Portugal (regional scale) show any structural alteration, which can reflect global changes during the last century. For this purpose, daily extremes of air‐surface temperatures, as well as the clustering of extreme temperatures defined by the peaks‐over‐random‐threshold (PORT) methodology, are strongly indicated to detect signals concerning global change. The analysis of meteorologically extreme events in Continental Portugal indicates that there has been a sizable change in their frequency. Even the experimental design, as presented here, does not allow an assessment of the reasons for these changes in frequency of temperature extremes, suggesting that natural variability in the climate system could be the cause of the recent changes, besides anthropogenic forcing due to the increase of greenhouse gas concentrations in the atmosphere. These findings can be linked to studies which have attempted to determine causing mechanisms, analysing large‐scale natural oscillations such as the North Atlantic Oscillation (NAO). Copyright © 2010 Royal Meteorological Society
Race, Ethnicity, Ancestry, and Pharmacogenetics
Authors: Urban Thomas J.
Published: March 2010

Pharmacogenetics is the study of how genetic variation influences the response to drugs. The concepts of race, ethnicity, and ancestry have long had a strong influence on pharmacogenetic discovery and on our understanding of population‐level differences in drug response. The primary goal of pharmacogenetics, however, is to identify the individual genetic determinants of drug activity so that therapy can be tailored to the individual patient. This article describes the relationship between the concepts of race, ethnicity, and ancestry and how these concepts have been applied to pharmacogenetics, and it provides examples of the benefits and pitfalls associated with the use of racial or ethnic labels in genetic studies. The future of pharmacogenetics, including the study of rare genetic variation and what this means for racial or ethnic disparities in pharmacogenetic discovery, is also discussed. Mt Sinai J Med 77:133–139, 2010. © 2010 Mount Sinai School of Medicine
Genetic and Environmental Contributions to Racial Disparities in Preterm Birth
Authors: Dolan Siobhan M.
Published: March 2010

The preterm birth rate exceeds 12% in the United States, and preterm birth continues to be a clinical and public health challenge globally. Even though preterm birth is a major contributor to infant mortality and lifelong morbidity, there are few effective strategies to predict preterm birth and few clinical interventions to prevent it. Genomic research approaches that identify risk factors at the intersection of genetics and the environment will likely provide insights. Both genetic and environmental factors are known to contribute to the racial disparity seen in preterm birth. Through the identification of relevant gene‐environment interactions that contribute to preterm birth and may underlie the racial disparity in preterm birth, research that will translate to clinical practice and ultimately prevent a number of preterm births is possible. Mt Sinai J Med 77:160–165, 2010. © 2010 Mount Sinai School of Medicine
Is There a Genetic Basis for Health Disparities in Human Immunodeficiency Virus Disease?
Authors: Winkler Cheryl
Published: March 2010

The highest global prevalence rates for human immunodeficiency virus and acquired immune deficiency syndrome have been recorded in southern Africa; in the United States, individuals of African descent are disproportionately affected by human immunodeficiency virus infection. Human immunodeficiency virus–infected individuals with African ancestry are also estimated to have a 17‐fold or greater risk for developing human immunodeficiency virus–associated nephropathy in comparison with their counterparts of non‐African descent. Several recent studies have implicated genetic alleles that are more frequent in populations of African descent and increase the risk of human immunodeficiency virus infection and the risk of human immunodeficiency virus–associated neuropathy (HIVAN). The supposition that persons of African descent are more susceptible to human immunodeficiency virus infection because of an underlying genetic predisposition is not supported by available evidence. However, strong, replicated data show that the increased risk for human immunodeficiency virus–associated nephropathy, as well as other major forms of kidney disease in individuals of African descent, is due in part to MYH9 (myosin, heavy chain 9, non‐muscle) renal disease susceptibility alleles that are very frequent throughout sub‐Saharan Africa but are infrequent or absent in non‐Africans. Selection, drift, and demographic events shape the allelic architecture of the human genome: it is expected that these events will be reflected in geographic‐specific differentiation in allele frequencies for a small subset of alleles that may be associated with either increased or reduced risk for complex and infectious diseases. Mt Sinai J Med 77:149–159, 2010. © 2010 Mount Sinai School of Medicine
Environmental Justice and the Health of Children
Authors: Landrigan Philip J. , Rauh Virginia A. , Galvez Maida P.
Published: March 2010

Environmental injustice is the inequitable and disproportionately heavy exposure of poor, minority, and disenfranchised populations to toxic chemicals and other environmental hazards. Environmental injustice contributes to disparities in health status across populations of differing ethnicity, race, and socioeconomic status. Infants and children, because of their unique biological vulnerabilities and age‐related patterns of exposure, are especially vulnerable to the health impacts of environmental injustice. These impacts are illustrated by sharp disparities across children of different racial and ethnic backgrounds in the prevalence of 3 common diseases caused in part by environmental factors: asthma, lead poisoning, and obesity. Documentation of linkages between health disparities and environmental injustice is an important step toward achieving environmental justice. Mt Sinai J Med 77:178–187, 2010. © 2010 Mount Sinai School of Medicine
Colonoscopy Versus Computed Tomography Colonography for Colorectal Cancer Screening
Authors: Akhtar Reza , Lee Michelle , Itzkowitz Steven H.
Published: March 2010

Colorectal cancer is second only to lung cancer as the leading cause of death among North Americans of both sexes. Although screening rates for colorectal cancer in the United States have increased over the past decade, these rates (in the range of 45%−60%) are still lower than the screening rates for breast cancer (approximately 80%). Optical colonoscopy has been recognized as the preferred method for colorectal cancer screening in the United States, but computed tomography colonography has recently been gaining favor. This article compares the 2 methods with respect to both advantages and disadvantages. Mt Sinai J Med 77:214–224, 2010. © 2010 Mount Sinai School of Medicine
Epigenetics in Women's Health Care
Authors: Pozharny Yevgeniya , Lambertini Luca , Clunie Garfield , Ferrara Lauren , Lee Men‐Jean
Published: March 2010

Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression. DNA methylation, histone modification, and RNA regulation are some of the mechanisms involved in epigenetic modification. Epigenetic changes are believed to be a result of changes in an organism's environment that result in fixed and permanent changes in most differentiated cells. Some environmental changes that have been linked to epigenetic changes include starvation, folic acid, and various chemical exposures. There are periods in an organism's life cycle in which the organism is particularly susceptible to epigenetic influences; these include fertilization, gametogenesis, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal‐child health. New data suggest that epigenetic influences might be involved in the regulation of fetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. Various epigenetic mechanisms may also be involved in the pathogenesis of preeclampsia and intrauterine growth restriction. Additionally, environmental exposures are being held responsible for causing epigenetic changes that lead to a disease process. Exposure to heavy metals, bioflavinoids, and endocrine disruptors, such as bisphenol A and phthalates, has been shown to affect the epigenetic memory of an organism. Their long‐term effects are unclear at this point, but many ongoing studies are attempting to elucidate the pathophysiological effects of such gene‐environment interactions. Mt Sinai J Med 77:225–235, 2010. © 2010 Mount Sinai School of Medicine
Sertoli Leydig cell ovarian tumour and gastric polyps as presenting features of Peutz–Jeghers syndrome
Authors: Howell Lisa , Bader Abdulgader , Mullassery Dhanya , Losty Paul , Auth Marcus , Kokai George
Published: March 2010

We report a case of Peutz–Jeghers syndrome (PJS) in a 2‐year old with precocious puberty secondary to a Sertoli–Leydig cell tumour. Family history of PJS and other neoplasms were discovered. The tumour was excised and the STK11 gene deletion identified in both patient and father. Screening revealed hamartomatous gastric polyps, which were removed. Current recommendations for screening of children with PJS begin at age 8 years, based on reported occurrence of complications 1. This report illustrates the importance of considering early screening, along with close clinical review and patient/parent education, for detection of life threatening neoplasms and complications. Pediatr Blood Cancer 2010;55:206–207. © 2010 Wiley‐Liss, Inc.