bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of neuropilin‐2 in the ipsilateral growth of midbrain dopaminergic axons
Authors: Torigoe Makio , Yamauchi Kenta , Tamada Atsushi , Matsuda Ikuo , Aiba Atsu , Castellani Valérie , Murakami Fujio 
Published: March 2013

AbstractAxonal projections in the CNS can be categorized as either crossed or uncrossed. Crossing and uncrossing of axons has been explained by attractive and repulsive molecules like Netrin‐1 and Slits, which are secreted by midline structures. However, uncrossed projections can be established even in double knockout mice of slit1 and slit2 or of roundabout1 (robo1) and robo2, two receptors for Slits. Here, we found that a novel mechanism mediated by Neuropilin‐2 (Nrp2) contributes to the formation of uncrossed projections of midbrain dopaminergic neurons (mDANs). Nrp2 transcriptional activities were detected in a subset of mDANs, and its protein was expressed in mDAN axons growing through the ipsilateral diencephalon. In nrp2lacZ/lacZ mice, mDAN axons aberrantly grew toward the ventral midline and even crossed it, suggesting that Nrp2 is necessary for the development of mDAN ipsilateral projections. We investigated the involvement of Semaphorin 3B (Sema3B) and Sema3F, two ligands of Nrp2, by analysing mDAN axon trajectories in single or double knockout mice. In both cases, mDAN axons still projected ipsilaterally, suggesting the involvement mechanisms independent of these Sema3s. Nrp2‐deficient mDAN axons retained their responsiveness to Slit2, demonstrating that aberrant mDAN axons in nrp2lacZ/lacZ mice were not indirectly mediated by alterations in Slit/Robo signaling. Taken together, our results indicate that a novel mechanism mediated by Nrp2 contributes to the establishment of uncrossed projections by mDAN axons.
Psychological treatment of dental anxiety among adults: a systematic review
Authors: Wide Boman Ulla , Carlsson Viktor , Westin Maria , Hakeberg Magnus 
Published: March 2013

The aim was to investigate the efficacy of behavioural interventions as treatment of dental anxiety/phobia in adults, by conducting a systematic review of randomized controlled trials (RCTs). The inclusion criteria were defined according to the Patients, Interventions, Controls, Outcome (PICO) methodology. The study samples had documented dental anxiety, measured using validated scales [the Dental Anxiety Scale (DAS) or the Dental Fear Survey (DFS)], or fulfilled the psychiatric criteria for dental phobia. Behavioural interventions included were based on cognitive behavioural therapy (CBT)/behavioural therapy (BT), and control conditions were defined as information, sedation, general anaesthesia, and placebo/no treatment. The outcome variables were level of dental anxiety, acceptance of conventional dental treatment, dental treatability ratings, quality of life and oral health‐related quality of life, and complications. This systematic review identified 10 RCT publications. Cognitive behavioural therapy/behavioural therapy resulted in a significant reduction in dental anxiety, as measured using the DAS (mean difference = −2.7), but the results were based on low quality of evidence. There was also some support that CBT/BT improves the patients' acceptance of dental treatment more than general anaesthesia does (low quality of evidence). Thus, there is evidence that behavioural interventions can help adults with dental anxiety/phobia; however, it is clear that more well‐designed studies on the subject are needed.
Whole genome sequencing identifies SCN2A mutation in monozygotic twins with Ohtahara syndrome and unique neuropathologic findings
Authors: Touma Marlin , Joshi Mugdha , Connolly Meghan C. , Ellen Grant P. , Hansen Anne R. , Khwaja Omar , Berry Gerard T. , Kinney Hannah C. , Poduri Annapurna , Agrawal Pankaj B. 
Published: March 2013

SummaryMutations in SCN2A gene cause a variety of epilepsy syndromes. We report a novel SCN2A‐associated epilepsy phenotype in monozygotic twins with tonic seizures soon after birth and a suppression‐burst electroencephalography (EEG) pattern. We reviewed the medical records, EEG tracings, magnetic resonance imaging (MRI), and neuropathologic findings, and performed whole genome sequencing (WGS) on Twin B's DNA and Sanger sequencing (SS) on candidate gene mutations. Extensive neurometabolic evaluation and early neuroimaging studies were normal. Twin A died of an iatrogenic cause at 2 weeks of life. His neuropathologic examination was remarkable for dentate‐olivary dysplasia and granule cell dispersion of the dentate gyrus. Twin B became seizure free at 8 months and was off antiepileptic drugs by 2 years. His brain MRI, normal at 2 months, revealed evolving brainstem and basal ganglia abnormalities at 8 and 15 months that resolved by 20 months. At 2.5 years, Twin B demonstrated significant developmental delay. Twin B's WGS revealed a heterozygous variant c.788C>T predicted to cause p.Ala263Val change in SCN2A and confirmed to be de novo in both twins by SS. In conclusion, we have identified a de novo SCN2A mutation as the etiology for Ohtahara syndrome in monozygotic twins associated with a unique dentate‐olivary dysplasia in the deceased twin.
Factors affecting the Haemophilia Joint Health Score in children with severe haemophilia
Authors: Bladen M. , Main E. , Hubert N. , Koutoumanou E. , Liesner R. , Khair K. 
Published: March 2013

SummaryJoint damage from bleeding episodes leads to physical or functional limitations in people with haemophilia. Various factors may influence the frequency and severity of joint damage. This study examined whether age, prophylaxis, history of high‐titre inhibitors (HTI) and bleeding events influenced the Haemophilia Joint Health Score (HJHS) in children. Medical and physiotherapy notes of boys with severe haemophilia, aged 4–18 years, were reviewed to identify factors associated with increased HJHS. The HJHS of 83 boys (median age: 11) ranged from 0 to 25, with 44/83 (53%) having a score of zero. The median HJHS was 0 (mean 2.6). In the non‐HTI group, the HJHS for boys on late prophylaxis was 2.68 times higher than those who started early and the HJHS was on average 10% higher for every additional recent bleed. In this group the odds of having a zero score fell by 30% for every year increase in age. Boys with a history of HTI had higher HJHS scores than the non‐HTI group, and age, number of recent bleeds and tolerized status were positively associated with HJHS. The score rose on average by 28% for every year of age and by 76% for non‐tolerized boys. This study provides further evidence supporting early prophylaxis use and the importance of immune tolerance therapy. The HJHS is a useful tool for identifying and tracking changes in joint health with respect to therapy or disease progression. With improvements in haemophilia treatment, the disproportionate number of zero scores will continue to make interpretation of the HJHS challenging.
von Willebrand factor contributes to longer half‐life of PEGylated factor VIII in vivo
Authors: Tang L. , Leong L. , Sim D. , Ho E. , Gu J.‐M. , Schneider D. , Feldman R. I. , Monteclaro F. , Jiang H. , Murphy J. E. 
Published: March 2013

SummaryPEGylation of B‐domain deleted factor VIII (PEG‐FVIII‐BDD) prolongs the half‐life of the molecule by approximately twofold in animals (Mei et al., Blood 2010; 116: 270). To investigate the role of von Willebrand factor (vWF) in the catabolism of PEG‐FVIII‐BDD in vivo, a FVIII‐BDD mutant (F8V), which is incapable of binding vWF, was generated by deleting the vWF‐binding region in the a3 domain of FVIIII‐BDD. F8V was expressed, purified and PEGylated by site‐specific conjugation. The biochemical and biological properties of F8V and PEGylated F8V (PEG‐F8V) were evaluated in vitro and in vivo. The specific activity of purified F8V by a chromogenic assay was similar to FVIII‐BDD and PEGylation had minimal impact on the specific activity of F8V in this assay. Analysis by Biacore indicated that both F8V and PEG‐F8V display greatly reduced vWF binding in vitro. Pharmacokinetic studies in FVIII knockout (HaemA) mice showed that the terminal half‐life (T1/2) of F8V was dramatically reduced relative to FVIII‐BDD (0.6 h vs. 6.03 h). PEGylation of F8V promoted a significant increase in T1/2, although PEGylation did not fully compensate for the loss in vWF binding. PEG‐F8V showed a shorter T1/2 than PEG‐FVIII‐BDD both in HaemA mice (7.7 h vs. 14.3 h) and in Sprague‐Dawley male rats (2.0 ± 0.3 h vs. 6.0 ± 0.5 h). These data demonstrated that vWF contributes to the longer T1/2 of PEG‐FVIII‐BDD. Furthermore, this suggests that the clearance of the FVIII:vWF complex, through vWF receptors, is not the sole factor which places an upper limit on the duration of PEG‐FVIII circulation in plasma.
Similarity in joint function limitation in Type 3 von Willebrand's disease and moderate haemophilia A
Authors: Sood S. L. , Cuker A. , Wang C. , Metjian A. D. , Chiang E. Y. , Soucie J. M. , Konkle B. A. ,   HTCN Study Investigators
Published: March 2013

SummaryType 3 von Willebrand's disease (VWD) is a rare bleeding diathesis with complete or near complete deficiency of von Willebrand factor (VWF) and low factor VIII (FVIII) levels. In contrast, only FVIII is decreased in haemophilia A (HA). Both disorders are complicated by arthropathy. The purpose of this study was to further clarify the roles of FVIII and VWF: Antigen (VWF:Ag) in joint range of motion (ROM) loss over time. We compared joint ROM loss and other bleeding manifestations in 100 Type 3 VWD subjects (FVIII<5%) and 1814 moderate HA subjects (FVIII 1–5%) within the U.S. Universal Data Collection (UDC) database. High rates of bleeding were reported at baseline. During follow‐up, moderate HA patients reported a joint (46% vs. 34%, P < 0.0001) or muscle bleed (27% vs. 16%, P < 0.0001) in a higher proportion of visits than VWD patients. Other bleeds, including mucosal, were reported in a greater proportion of visits among patients with Type 3 VWD than among those with HA (49% vs. 32%, P < 0.0001). Multivariate analysis revealed no difference in joint ROM loss over time in the Type 3 VWD vs. moderate HA populations. A higher FVIII level was protective in both VWD and HA (P < 0.001). Our findings support the hypothesis of primacy of the FVIII level in determining risk of joint haemorrhage, and may help target therapy in Type 3 VWD and moderate HA to prevent joint disability.
Female resistance behaviour and progeny sex ratio in two Bradysia species (Diptera: Sciaridae) with paternal genome elimination
Authors: Featherston R. , Jones T. M. , Elgar M. A. 
Published: March 2013

AbstractThe relationship between female mating preferences and sex allocation has received considerable theoretical and empirical support. Typically, choosier females adjust their progeny sex ratio towards sons, who inherit the attractive traits of their father. However, in species with paternal genome elimination, where male sperm do not contain the paternal genome, predictions for the direction of progeny sex ratio biases and their relationship with female choosiness are atypical. Paternal genome elimination also creates a potential for male–female conflict over sex allocation, and any influence of female mate choice on sex ratio outcomes have interesting implications for sexually antagonistic coevolution. Within the Sciaridae (Diptera) are species that produce single‐sex progeny (monogenic species) and others in which progeny comprise both sexes (digenic species). Paternal genome elimination occurs in both species. We explore female mate resistance behaviour in a monogenic and digenic species of mushroom gnat from the genus Bradysia. Our experiments confirmed our theoretical predictions, revealing that in the monogenic and digenic species, females producing female‐biased progeny were more likely to have resisted at least one mating attempt.
Adoption of Self‐Protective Behaviors in Response to a Foodborne Illness Outbreak: Perspectives of Older Adults
Authors: SteelFisher Gillian , Blendon Robert , Hero Joachim , Ben‐Porath Eran 
Published: March 2013

AbstractUsing national polling data from the U.S.A., this study assessed differences between older (>64) and younger (18–64) adults in their levels of concern about getting sick from a hypothetical outbreak and their likelihood of adopting each of several protective behaviors in response to a warning and a recall. Concern levels among older adults were lower than younger adults when outbreak‐related illnesses were reported in the same state or town as the respondent, but concern among both increased as cases were reported in closer geographic proximity. Majorities of both older and younger adults reported that they were very likely to adopt a range of recommended protective behaviors, but older adults were less likely to adopt many. For example, if the outbreak was described as mild (no deaths), older adults were less likely to stop purchasing affected items and throw out affected items in the home. Under a severe scenario (with deaths), older adults were also less likely to take several actions, including throwing out the affected item, not purchasing the affected item at stores that sell groceries and not ordering the affected item in restaurants.Practical ApplicationsThe findings from this study suggest there need to be improved communications to older adults in regard to foodborne illness outbreaks. Future communications should focus more on providing actionable information regarding ways that consumers can change their behavior to reduce their risk of infection. For example, it may be important to highlight clear directions for identifying recalled units of foods or drinks so older adults can easily find them if they are in their own kitchens. Communications should also include channels that are better targeted toward older consumers, such as networks of senior services. Materials should follow guidelines that have been shown to be effective with older adults, such as including basic changes like larger font sizes and clear graphics on printed materials.
When Comorbidity, Aging, and Complexity of Primary Care Meet: Development and Validation of the Geriatric CompleXity of Care Index
Authors: Min Lillian , Wenger Neil , Walling Anne M. , Blaum Caroline , Cigolle Christine , Ganz David A. , Reuben David , Shekelle Paul , Roth Carol , Kerr Eve A. 
Published: March 2013

ObjectivesTo develop and validate the Geriatric CompleXity of Care Index (GXI), a comorbidity index of medical, geriatric, and psychosocial conditions that addresses disease severity and intensity of ambulatory care for older adults with chronic conditions.DesignDevelopment phase: variable selection and rating by clinician panel. Validation phase: medical record review and secondary data analysis.SettingAssessing the Care of Vulnerable Elders‐2 study.ParticipantsSix hundred forty‐four older (≥75) individuals receiving ambulatory care.MeasuresDevelopment: 32 conditions categorized according to severity, resulting in 117 GXI variables. A panel of clinicians rated each GXI variable with respect to the added difficulty of providing primary care for an individual with that condition. Validation: Modified versions of previously validated comorbidity measures (simple count, Charlson, Medicare Hierarchical Condition Category), longitudinal clinical outcomes (functional decline, survival), intensity of ambulatory care (primary, specialty care visits, polypharmacy, number of eligible quality indicators (NQI)) over 1 year of care.ResultsThe most‐morbid individuals (according to quintiles of GXI) had more visits (7.0 vs 3.7 primary care, 6.2 vs 2.4 specialist), polypharmacy (14.3% vs 0% had ≥14 medications), and greater NQI (33 vs 25) than the least‐morbid individuals. Of the four comorbidity measures, the GXI was the strongest predictor of primary care visits, polypharmacy, and NQI (P < .001, controlling for age, sex, function‐based vulnerability).ConclusionOlder adults with complex care needs, as measured by the GXI, have healthcare needs above what previously employed comorbidity measures captured. Healthcare systems could use the GXI to identify the most complex elderly adults and appropriately reimburse primary providers caring for older adults with the most complex care needs for providing additional visits and coordination of care.
Venous Thromboembolism After Joint Replacement in Older Male Veterans with Comorbidity
Authors: Kapoor Alok , Chew Priscilla , Silliman Rebecca A. , Hylek Elaine M. , Katz Jeffrey N. , Cabral Howard , Berlowitz Dan 
Published: March 2013

ObjectivesTo identify older adults with comorbidities or poor functional status at high risk of postoperative venous thromboembolism (VTE).DesignRetrospective cohort study.SettingVeterans Affairs Medical Center (VAMC).ParticipantsOlder adults who underwent total hip and knee replacement (THR and TKR) from 2002 to 2009.MeasurementsUsing multivariate logistic regression, the independent effect of cardiopulmonary comorbidities and diabetes on VTE was analyzed. Functional status expressed in a summary physical component score (PCS) was also analyzed in a subset of individuals in whom information on it was available.ResultsThere were 23,326 THR and TKR surgeries performed at the VAMC during the study period. Individuals with chronic obstructive pulmonary disease (COPD) had a 25% greater risk of VTE (odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.06–1.48), whereas those with coronary artery disease, congestive heart failure, and cerebrovascular disease did not have a greater risk of VTE. Individuals with diabetes mellitus had a lower risk of VTE (OR = 0.77, 95% CI = 0.64–0.92). Individuals with low PCS, which were available for 3,169 patients, had a 62% greater risk, although the effect did not reach statistical significance (lowest vs highest quartile OR = 1.62, 95% CI = 0.93–2.80).ConclusionIndividuals with COPD had slightly greater risk of VTE, whereas low functional status had a larger effect that did not reach statistical significance. The constraints of administrative data analysis and sample size available for PCS limit conclusions about the role of these comorbidities and functional status.
Contributions of Basal and Prandial Hyperglycemia to Total Hyperglycemia in Older and Younger Adults with Type 2 Diabetes Mellitus
Authors: Munshi Medha N. , Pandya Naushira , Umpierrez Guillermo E. , DiGenio Andres , Zhou Rong , Riddle Matthew C. 
Published: March 2013

ObjectivesTo evaluate the relative contributions of basal and prandial components to total hyperglycemia in older and younger adults with type 2 diabetes mellitus.DesignParticipant‐level data were pooled from six randomized studies of 24 weeks or longer treatment with insulin glargine or an active comparator.SettingProspective, randomized Phase 3 or 4 controlled trials.ParticipantsOne thousand six hundred ninety‐nine individuals: 509 (30%) aged 65 and older and 1,190 (70%) younger than 65.MeasurementsContributions of basal hyperglycemia (BHG) and postprandial hyperglycemia (PPHG) to total hyperglycemia, defined as the incremental area under the curve of daytime blood glucose (BG) from the overall glucose profile calculated from 7‐point self‐measured BG profiles, of participants aged 65 and older were compared with those of participants younger than 65.ResultsAfter 24 weeks of treatment, glycosylated hemoglobin (HbA1c) decreased in the older (8.6–7.0%) and younger (8.7–7.1%) groups; the relative contribution of BHG was significantly lower in both age groups (P < .001). The relative contribution of BHG to that of PPHG was significantly smaller in older than in younger participants at baseline (75.4% vs 79.4%; P < .001) and 24 weeks (37.6% vs 44.7%; P < .001). The relative contribution of BHG to total hyperglycemia was not correlated with HbA1c at baseline and after 24 weeks of treatment in older participants but was positively correlated at baseline (correlation coefficient (r) = 0.082; P = .005) and 24 weeks (r = 0.062; P = .03) in younger participants. A significantly lower proportion of older participants reported symptomatic, glucose‐confirmed, and nocturnal hypoglycemia during 24 weeks of treatment (P < .001).ConclusionThe relative contribution of BHG was lower, and that of PPHG was greater in older than in younger participants, suggesting that different therapeutic approaches may be required to treat hyperglycemia effectively in these different age groups.
Spontaneous high‐grade glial intramedullary tumor of the spine in a rhesus macaque (Macaca mulatta)
Authors: Hanley P.W. , Wilkerson G.K. , Bernacky B.J. , Barnhart K.F. , Baze W.B. , McArthur M.J. 
Published: March 2013

AbstractBackgroundA 4‐year‐old rhesus macaque presented with acute, progressive paresis of the extremities.MethodsA complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed.ResultsThe clinical, histopathological, and immunohistochemical findings confirmed a high‐grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma.ConclusionsWe describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non‐human primate.
AMPK involvement in endoplasmic reticulum stress and autophagy modulation after fatty liver graft preservation: a role for melatonin and trimetazidine cocktail
Authors: Zaouali Mohamed Amine , Boncompagni Eleonora , Reiter Russel J. , Bejaoui Mohamed , Freitas Isabel , Pantazi Eirini , Folch‐Puy Emma , Abdennebi Hassen ben , Garcia‐Gil Francisco A. , Roselló‐Catafau Joan 
Published: March 2013

AbstractIschemia/reperfusion injury (IRI) associated with liver transplantation plays an important role in the induction of graft injury. Prolonged cold storage remains a risk factor for liver graft outcome, especially when steatosis is present. Steatotic livers exhibit exacerbated endoplasmic reticulum (ER) stress that occurs in response to cold IRI. In addition, a defective liver autophagy correlates well with liver damage. Here, we evaluated the combined effect of melatonin and trimetazidine as additives to IGL‐1 solution in the modulation of ER stress and autophagy in steatotic liver grafts through activation of AMPK. Steatotic livers were preserved for 24 hr (4°C) in UW or IGL‐1 solutions with or without MEL + TMZ and subjected to 2‐hr reperfusion (37°C). We assessed hepatic injury (ALT and AST) and function (bile production). We evaluated ER stress (GRP78, PERK, and CHOP) and autophagy (beclin‐1, ATG7, LC3B, and P62). Steatotic livers preserved in IGL‐1 + MEL + TMZ showed lower injury and better function as compared to those preserved in IGL‐1 alone. IGL‐1 + MEL + TMZ induced a significant decrease in GRP78, pPERK, and CHOP activation after reperfusion. This was consistent with a major activation of autophagic parameters (beclin‐1, ATG7, and LC3B) and AMPK phosphorylation. The inhibition of AMPK induced an increase in ER stress and a significant reduction in autophagy. These data confirm the close relationship between AMPK activation and ER stress and autophagy after cold IRI. The addition of melatonin and TMZ to IGL‐1 solution improved steatotic liver graft preservation through AMPK activation, which reduces ER stress and increases autophagy.