bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complications in MS Patients after CCSVI Procedures Abroad (Calgary, AB)
Authors: Burton Jodie M. , Alikhani Katayoun , Goyal Mayank , Costello Fiona , White Chris , Patry David , Bell Robert , Hill Michael D. 
Published: February 2016

ABSTRACT:Background:The “chronic cerebrospinal venous insufficiency” or “CCSVI” hypothesis, namely that multiple sclerosis (MS) is caused by abnormalities in the azygous and internal jugular veins with subsequent alterations in venous hemodynamics in the central nervous system, has been a dominant topic in MS care in Canada over the past year. Although there is no methodologically rigorous evidence to support this hypothesis presently, a considerable number of MS patients have undergone endovascular CCSVI procedures. Such procedures include angioplasty or stent placement in jugular and azygous veins. The safety and efficacy of these procedures is unknown, but not without risk.Methods:Chart and patient review of five patients with confirmed MS followed in Calgary were undertaken after patients came to medical attention by referral or admission secondary to complications believed to be associated with CCSVI procedures.Results:Complications upon investigation and review included internal jugular vein stent thrombosis, cerebral sinovenous thrombosis, stent migration, cranial nerve injury and injury associated with venous catheterization.Conclusions:As the debate about CCSVI and its relationship to MS continues, the complications and risks associated with venous stenting and angioplasty in jugular and azygous veins are becoming clearer. As increasing numbers of MS patients are seeking such procedures, these five cases represent the beginning of a wave of complications for which standardized care guidelines do not exist. Our experience and that of our colleagues will be used to develop guidelines and strategies to monitor and manage these patients as their numbers increase.
Founder Mutation for a-sarcoglycan-LGMD2D in a Magdalen Islands Acadian Cluster
Authors: Tétreault M. , Srour M. , Allyson J. , Thiffault I. , Loisel L. , Robitaille Y. , Bouchard JP. , Brais B. 
Published: February 2016

ABSTRACT:Background:We have recruited a group of four living and reviewed the records of six deceased distantly related French-Canadians of Acadian descent affected by a childhood-onset form of recessive limb-girdle muscular dystrophy (LGMD). All cases originate from the small archipelago of the Magdalen Islands (population: 13,000) isolated in the Gulf of St-Lawrence.Methods:Based on the likely sharing of the same founder mutation we completed a 319K SNPs genome-wide scan to identify the disease locus and then screen candidate genes in this region.Results:All patients had normal initial motor milestones. They presented with limb girdle weakness at the average age of seven years (5-11). Progressive weakness led to loss of ambulation at a wide range of ages (10-39). Patients also developed macroglossia, large calves and mild to moderate contractures, hyperlordosis and decreased pulmonary function. Creatine kinase levels were elevated (1,800-10,000 U/L) in the first decades, but decreased with progression of disease. Homozygosity mapping uncovered a shared chromosomal region of 6.33Mb. The alpha sarcoglycan (SGCA) gene, mutated in LGMD2D, lay in this candidate interval. Sequencing of all SGCA exons uncovered a shared homozygous missense mutation (c.229C>T, p.R77C), the most common SGCA mutation internationally reported. Using demographic data, we estimated a high carrier rate of 1/22.Conclusion:The p.R77C mutation has also been observed in many populations, including in France and Spain (Basques). This corresponds to the first reported recessive founder disease for the Magdalen Islands, an archipelago settled in the XlXth century, largely by Acadian immigrants.
An International Needs Assessment of Caregivers for Frontotemporal Dementia
Authors: Chow Tiffany W. , Pio Fabricio J. , Rockwood Kenneth 
Published: February 2016

ABSTRACT:Objective:To guide development of public awareness and caregiver support resources for frontotemporal dementia (FTD) syndromes.Methods:We used an online survey to explore their needs. The survey was self-administered by self-identified, English-speaking caregivers for patients with FTD in several countries.Results:Of 79 caregiver respondents, approximately half were caring for patients with behavioural variant FTD or semantic dementia. The most common initial symptoms were Changes in Thinking and Judgment. Half of the respondents identified “failure to recognize the early stage of illness as a dementia” as the most troublesome aspect. Accordingly, over 40% of respondents had difficulty obtaining an accurate diagnosis for the patient. Caregivers prioritized family counseling and the public educational message that dementia can affect young people.Conclusion:The largest international survey of FTD caregivers to-date showed that support is needed for all family members adapting to the shock of early-onset dementia, and this may be most readily provided online.
The Utility of Self-Report Measures and the Continuous Performance Test in the Diagnosis of ADHD in Adults
Authors: Solanto Mary V. , Etefia Kenneth , Marks David J. 
Published: February 2016

ABSTRACTBackground: Attention-deficit/hyperactivity disorder (ADHD) occurs in as many as 4% of adults yet it is often not recognized in clinical settings because the presenting symptoms may resemble those seen in other disorders or because symptoms may be masked by commonly comorbid conditions such as anxiety and depression.Objective: The purpose of this study was to examine the diagnostic utility of instruments commonly used in the assessment of adults presenting with symptoms of ADHD.Methods: We reviewed several widely used self-report and laboratory measures and empirically examined the utility of the Brown Attention-Deficit Disorder Scale for Adults (Brown ADD Scale) and the Conners Continuous Performance Test (CPT) in differentially identifying adults with ADHD and those with other Axis I disorders.Results:Ninety-three adults who self-referred to the ADHD program for adults at a university medical center participated in the study. Of these, 44 had ADHD combined subtype (ADHD-CB), and 26 had ADHD, predominantly inattentive subtype (ADHD-IA). Thirty-three non-ADHD adults diagnosed with Axis I mood or anxiety disorders comprised an “Other Psychiatric” group. Rates of comorbid disorders, including substance abuse, in the ADHD groups were typical of those reported in the adult ADHD literature. Data on the Brown ADD Scale and on the CPT were available for subsets of 61 and 46 participants, respectively. Analyses showed that the ADHD-CB, ADHD-IA, and Other Psychiatric groups all received mean scores in the clinical range on the Brown ADD Scale, with a trend toward even higher elevations in the two ADHD groups. Among 12 CPT variables assessed for the three groups, the mean scores on only two variables for the ADHD-IA group were clinically elevated. Neither the Brown ADD Scale nor CPT scores evinced sufficient sensitivity and specificity to qualify them to assist in differential diagnosis of ADHD vis-a-vis other, predominantly internalizing, psychiatric disorders.Conclusion: The results indicate a need for closer examination of executive and adaptive functioning in adults with ADHD compared with those with internalizing disorders in order to identify features that could assist in differential diagnosis.
Brain Network Organization and Social Executive Performance in Frontotemporal Dementia
Authors: Sedeño Lucas , Couto Blas , García-Cordero Indira , Melloni Margherita , Baez Sandra , Morales Sepúlveda Juan Pablo , Fraiman Daniel , Huepe David , Hurtado Esteban , Matallana Diana , Kuljis Rodrigo , Torralva Teresa , Chialvo Dante , Sigman Mariano , Piguet Olivier , Manes Facundo , Ibanez Agustin 
Published: February 2016

AbstractObjectives:Behavioral variant frontotemporal dementia (bvFTD) is characterized by early atrophy in the frontotemporoinsular regions. These regions overlap with networks that are engaged in social cognition-executive functions, two hallmarks deficits of bvFTD. We examine (i) whether Network Centrality (a graph theory metric that measures how important a node is in a brain network) in the frontotemporoinsular network is disrupted in bvFTD, and (ii) the level of involvement of this network in social-executive performance.Methods:Patients with probable bvFTD, healthy controls, and frontoinsular stroke patients underwent functional MRI resting-state recordings and completed social-executive behavioral measures.Results:Relative to the controls and the stroke group, the bvFTD patients presented decreased Network Centrality. In addition, this measure was associated with social cognition and executive functions. To test the specificity of these results for the Network Centrality of the frontotemporoinsular network, we assessed the main areas from six resting-state networks. No group differences or behavioral associations were found in these networks. Finally, Network Centrality and behavior distinguished bvFTD patients from the other groups with a high classification rate.Conclusions:bvFTD selectively affects Network Centrality in the frontotemporoinsular network, which is associated with high-level social and executive profile. (JINS, 2016,22, 250–262)
Salience and Default Mode Network Coupling Predicts Cognition in Aging and Parkinson’s Disease
Authors: Putcha Deepti , Ross Robert S. , Cronin-Golomb Alice , Janes Amy C. , Stern Chantal E. 
Published: February 2016

AbstractObjectives:Cognitive impairment is common in Parkinson’s disease (PD). Three neurocognitive networks support efficient cognition: the salience network, the default mode network, and the central executive network. The salience network is thought to switch between activating and deactivating the default mode and central executive networks. Anti-correlated interactions between the salience and default mode networks in particular are necessary for efficient cognition. Our previous work demonstrated altered functional coupling between the neurocognitive networks in non-demented individuals with PD compared to age-matched control participants. Here, we aim to identify associations between cognition and functional coupling between these neurocognitive networks in the same group of participants.Methods:We investigated the extent to which intrinsic functional coupling among these neurocognitive networks is related to cognitive performance across three neuropsychological domains: executive functioning, psychomotor speed, and verbal memory. Twenty-four non-demented individuals with mild to moderate PD and 20 control participants were scanned at rest and evaluated on three neuropsychological domains.Results:PD participants were impaired on tests from all three domains compared to control participants. Our imaging results demonstrated that successful cognition across healthy aging and Parkinson’s disease participants was related to anti-correlated coupling between the salience and default mode networks. Individuals with poorer performance scores across groups demonstrated more positive salience network/default-mode network coupling.Conclusions:Successful cognition relies on healthy coupling between the salience and default mode networks, which may become dysfunctional in PD. These results can help inform non-pharmacological interventions (repetitive transcranial magnetic stimulation) targeting these specific networks before they become vulnerable in early stages of Parkinson’s disease. (JINS, 2016,22, 205–215)
Variation in White Matter Connectivity Predicts the Ability to Remember Faces and Discriminate Their Emotions
Authors: Unger Ashley , Alm Kylie H. , Collins Jessica A. , O’Leary Jacquelyn M. , Olson Ingrid R. 
Published: February 2016

AbstractObjectives: The extended face network contains clusters of neurons that perform distinct functions on facial stimuli. Regions in the posterior ventral visual stream appear to perform basic perceptual functions on faces, while more anterior regions, such as the ventral anterior temporal lobe and amygdala, function to link mnemonic and affective information to faces. Anterior and posterior regions are interconnected by a long-range white matter tracts; however, it is not known if variation in connectivity of these pathways explains cognitive performance. Methods: Here, we used diffusion imaging and deterministic tractography in a cohort of 28 neurologically normal adults ages 18–28 to examine microstructural properties of visual fiber pathways and their relationship to certain mnemonic and affective functions involved in face processing. We investigated how inter-individual variability in two tracts, the inferior longitudinal fasciculus (ILF) and the inferior fronto-occipital fasciculus (IFOF), related to performance on tests of facial emotion recognition and face memory. Results: Results revealed that microstructure of both tracts predicted variability in behavioral performance indexed by both tasks, suggesting that the ILF and IFOF play a role in facilitating our ability to discriminate emotional expressions in faces, as well as to remember unique faces. Variation in a control tract, the uncinate fasciculus, did not predict performance on these tasks. Conclusions: These results corroborate and extend the findings of previous neuropsychology studies investigating the effects of damage to the ILF and IFOF, and demonstrate that differences in face processing abilities are related to white matter microstructure, even in healthy individuals. (JINS, 2016, 22, 180–190)
The Same Difference: Protecting Same-Sex Couples under the Domestic Violence Ordinance
Authors: Kapai Puja 
Published: February 2016

AbstractHong Kong recently amended its Domestic Violence Ordinance (“DVO”). During the deliberations, the issue of whether protection under the DVO ought to be extended to same-sex couples arose for discussion and has since been the subject of extensive debate. Religious and conservative groups have argued that including these groups within the DVO risks overhauling the traditional meaning of “family” and could implicitly legitimize same-sex marriage whilst others have insisted that failing to provide equivalent civil remedies under the DVO to such groups amounts to sexual orientation discrimination and is contrary to Hong Kong's international human rights commitments. This paper reviews the various arguments that have been raised against the inclusion of same-sex couples within the DVO and argues that Hong Kong's international and constitutional commitments to the principles of equality and non-discrimination require that samesex couples be brought within the purview of this legislation.
The Validation of a Spanish Version of the Multidimensional Inventory of Religious/Spiritual Well-Being in Mexican College Students
Authors: Berger Daniela , Fink Andreas , Perez Gomez Maria Margarita , Lewis Andrew , Unterrainer Human-Friedrich 
Published: February 2016

AbstractAfter the Multidimensional Inventory for Religious/Spiritual Well-Being (MI-RSWB) was validated as a reliable instrument for the Western European context it is primarily intended in this study to translate the measure into Spanish and adapt it for the Mexican culture. Furthermore we investigate whether spirituality/religiosity has a similar impact on indicators of personality and subjective well-being in Mexico as it does in samples drawn from Western European cultures. 190 students (99 females) from public and private universities in Guadalajara, all Mexican citizens, were involved in this study. We found strong evidential support for the six factor solution of the Original MI-RSWB in this Mexican population. By mirroring previous research the measure showed a highly satisfying internal consistency (α = .91 for the total score and .75 or higher for all six sub dimensions). Furthermore the total RSWB score was observed to be related with Eysenck’s personality dimensions Extraversion (r = .24, p < .01), and Psychoticism (r = –.28, p < .001), although not with Neuroticism. There was also a positive correlation with Sense of Coherence (r = .31, p < .001). In conclusion, the dimensionality of RSWB and its associations with personality and subjective well-being was well supported in this first application within a Mexican cultural context.
Drug screening on Hutchinson Gilford progeria pluripotent stem cells reveals aminopyrimidines as new modulators of farnesylation
Authors: Blondel S , Egesipe A-L , Picardi P , Jaskowiak A-L , Notarnicola M , Ragot J , Tournois J , Le Corf A , Brinon B , Poydenot P , Georges P , Navarro C , pitrez P R , Ferreira L , Bollot G , Bauvais C , Laustriat D , Mejat A , De Sandre-Giovannoli A , Levy N , Bifulco M , Peschanski M , Nissan X 
Published: February 2016

AbstractHutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by a dramatic appearance of premature aging. HGPS is due to a single-base substitution in exon 11 of the LMNA gene (c.1824C>T) leading to the production of a toxic form of the prelamin A protein called progerin. Because farnesylation process had been shown to control progerin toxicity, in this study we have developed a screening method permitting to identify new pharmacological inhibitors of farnesylation. For this, we have used the unique potential of pluripotent stem cells to have access to an unlimited and relevant biological resource and test 21 608 small molecules. This study identified several compounds, called monoaminopyrimidines, which target two key enzymes of the farnesylation process, farnesyl pyrophosphate synthase and farnesyl transferase, and rescue in vitro phenotypes associated with HGPS. Our results opens up new therapeutic possibilities for the treatment of HGPS by identifying a new family of protein farnesylation inhibitors, and which may also be applicable to cancers and diseases associated with mutations that involve farnesylated proteins.
The anticancer effect of chaetocin is enhanced by inhibition of autophagy
Authors: Jung H-J , Seo I , Casciello F , Jacquelin S , Lane S W , Suh S-Il , Suh M-H , Lee J S , Baek W-K 
Published: February 2016

AbstractChaetocin is a fungal metabolite that possesses a potent antiproliferative activity in solid tumors by inducing cell death. Although recent studies have extended the role of chaetocin in tumors, the underlying molecular mechanisms such as the downstream cascade that induces cell death has not clearly been elucidated. In this study, we show that chaetocin is able to induce both apoptosis and autophagy in several hepatoma cell lines including HepG2, Hep3B and Huh7 cell lines. Moreover, we found that the inhibition of caspase-3/7 activity by z-VAD-fmk treatment was able to block chaetocin-mediated cell death, whereas blocking autophagy by Bafilomycin A1 or the knockdown of autophagy protein 5 enhanced cell death mediated by chaetocin. These findings suggest that chaetocin has a potent anticancer effect against hepatoma. Inhibition of autophagy may potentiate anticancer effects of chaetocin thus providing evidence that combined treatment with chaetocin and autophagy inhibitors will be an effective strategy for treating cancer.
AIMP1 downregulation restores chondrogenic characteristics of dedifferentiated/degenerated chondrocytes by enhancing TGF-β signal
Authors: Ahn J , Kumar H , Cha B-H , Park S , Arai Y , Han I , Park S G , Lee S-H 
Published: February 2016

AbstractDedifferentiation and degeneration of chondrocytes critically influences the efficiency of cartilage repair. One of the causes is the defect of transforming growth factor (TGF)-βsignaling that promotes chondrogenic differentiation and degeneration. In the present study, we found that aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) negatively regulates TGF-βsignaling via interactions with Smad2 and Smad3 in immunoprecipitation assay and luciferase assay. In addition, we observed that the AIMP1 expression level was significantly increased in osteoarthritis (OA) patient-derived degenerated chondrocytes compared with healthy control. So, we hypothesized that downregulation of AIMP1 using small-interfering RNA (siRNA) technology in dedifferentiated (collected at passage #6) and degenerated (obtained from OA-affected areas) chondrocytes could lead to recover TGF-βsignaling in both chondrocytes. Indeed, AIMP1 downregulation restored TGF-βsignaling by promoting phosphorylation of Smad2 and Smad3, which shows redifferentiated characteristics in both dedifferentiated and degenerated chondrocytes. Additionally, implantation analyses usingin vivomouse model clearly showed that AIMP1 downregulation resulted in the increased chondrogenic potential as well as the enhanced cartilage tissue formation in both dedifferentiated and degenerated chondrocytes. Histological analyses clarified that AIMP1 downregulation increased expression levels of collagen type II (Col II) and aggrecan, but not Col I expression. Taken together, these data indicate that AIMP1 downregulation using siRNA is a novel tool to restore TGF-βsignaling and thereby increases the chondrogenic potential of dedifferentiated/degenerated chondrocytes, which could be further developed as a therapeutic siRNA to treat OA.
Altered Kv2.1 functioning promotes increased excitability in hippocampal neurons of an Alzheimer’s disease mouse model
Authors: Frazzini V , Guarnieri S , Bomba M , Navarra R , Morabito C , Mariggiò M A , Sensi S L 
Published: February 2016

AbstractAltered neuronal excitability is emerging as an important feature in Alzheimer’s disease (AD). Kv2.1 potassium channels are important modulators of neuronal excitability and synaptic activity. We investigated Kv2.1 currents and its relation to the intrinsic synaptic activity of hippocampal neurons from 3xTg-AD (triple transgenic mouse model of Alzheimer's disease) mice, a widely employed preclinical AD model. Synaptic activity was also investigated by analyzing spontaneous [Ca2+]i spikes. Compared with wild-type (Non-Tg (non-transgenic mouse model)) cultures, 3xTg-AD neurons showed enhanced spike frequency and decreased intensity. Compared with Non-Tg cultures, 3xTg-AD hippocampal neurons revealed reduced Kv2.1-dependent Ik current densities as well as normalized conductances. 3xTg-AD cultures also exhibited an overall decrease in the number of functional Kv2.1 channels. Immunofluorescence assay revealed an increase in Kv2.1 channel oligomerization, a condition associated with blockade of channel function. In Non-Tg neurons, pharmacological blockade of Kv2.1 channels reproduced the altered pattern found in the 3xTg-AD cultures. Moreover, compared with untreated sister cultures, pharmacological inhibition of Kv2.1 in 3xTg-AD neurons did not produce any significant modification in Ik current densities. Reactive oxygen species (ROS) promote Kv2.1 oligomerization, thereby acting as negative modulator of the channel activity. Glutamate receptor activation produced higher ROS levels in hippocampal 3xTg-AD cultures compared with Non-Tg neurons. Antioxidant treatment with N-Acetyl-Cysteine was found to rescue Kv2.1-dependent currents and decreased spontaneous hyperexcitability in 3xTg-AD neurons. Analogous results regarding spontaneous synaptic activity were observed in neuronal cultures treated with the antioxidant 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our study indicates that AD-related mutations may promote enhanced ROS generation, oxidative-dependent oligomerization, and loss of function of Kv2.1 channels. These processes can be part on the increased neuronal excitability of these neurons. These steps may set a deleterious vicious circle that eventually helps to promote excitotoxic damage found in the AD brain.