bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurosarcoidosis‐related intracranial haemorrhage: three new cases and a systematic review of the literature
Authors: O'Dwyer J. P. , Al‐Moyeed B. A. , Farrell M. A. , Pidgeon C. N. , Collins D. R. , Fahy A. , Gibney J. , Swan N. , Dempsey O. J. , Kidd D. P. , Reid J. M. , Smyth S. , McCabe D. J. H. 
Published: June 2012

Background and purposeIntracranial haemorrhage in neurosarcoidosis (NS‐ICH) is rare, poorly understood and the diagnosis of NS may not be immediately apparent.MethodsThe clinical features of three new NS‐ICH cases are described including new neuropathological findings and collated with cases from a systematic literature review.ResultsCases: (i) A 41‐year‐old man with headaches, hypoandrogenism and encephalopathy developed a cerebellar haemorrhage. He had neuropathological confirmation of NS with biopsy‐proven angiocentric granulomata and venous disruption. He responded to immunosuppressive therapy. (ii) A 41‐year‐old man with no history of hypertension was found unconscious. A subsequently fatal pontine haemorrhage was diagnosed. Liver biopsy revealed sarcoid granulomas. (iii) A 36‐year‐old man with raised intracranial pressure headaches presented with a seizure and a frontal haemorrhage. Hilar lymph node biopsy confirmed sarcoidosis, and he was treated successfully. Systematic review: Twelve other published cases were identified and collated with our cases. Average age was 36 years and M:F = 2.3:1; 46% presented with neurological symptoms and 31% had CNS‐isolated disease. Immediate symptoms of ICH were acute/worsening headache or seizures (60%). ICH was supratentorial (62%), infratentorial (31%) or subarachnoid (7%). Forty percent had definite NS, 53% probable NS and 7% possible NS (Zajicek criteria). Antigranulomatous/immunosuppressive therapy regimens varied and 31% died.ConclusionsThis series expands our knowledge of the pathology of NS‐ICH, which may be of arterial or venous origin. One‐third have isolated NS. Clinicians should consider NS in young‐onset ICH because early aggressive antigranulomatous therapy may improve outcome.
Whole genome amplification in large neurons of the terrestrial slug Limax
Authors: Yamagishi Miki , Ito Etsuro , Matsuo Ryota 
Published: June 2012

J. Neurochem. (2012) 122, 727–737.AbstractThe brain of gastropod mollusks contains giant neurons whose nuclei are enlarged with a large amount of genomic DNA. Such DNA is produced by repeated endoreplication. We have previously demonstrated that the frequency of the neuronal DNA endoreplication is correlative to the body growth of the adult land slug and to the increase in the amount of transcripts within the neuron. However, it has long been controversial whether the neuronal DNA endoreplication entails whole genome amplification (polyploidy), or whether only the necessary genomic loci are amplified (polyteny, polysomy, or cis‐amplification by unequal recombination). In the present study, we adopted two modern techniques – quantitative genomic PCR and 5′‐bromodeoxyuridine labeling – to distinguish between these two possibilities. Our results demonstrated that multiple genomic loci were amplified to the same extent irrespective of the transcriptional activities at these loci. Moreover, the visceral giant cell, the biggest neuron in the slug’s brain, was estimated to contain approximately 10 000‐times as much genomic DNA as the haploid amount. The 5′‐bromodeoxyuridine‐labeling experiments also revealed a uniform DNA synthesis within the nucleus. These results strongly support the idea that the giant neurons contain a polyploid genome rather than a locus‐specific amplified genome.
Vimentin participates in microglia activation and neurotoxicity in cerebral ischemia
Authors: Jiang Susan X. , Slinn Jacqueline , Aylsworth Amy , Hou Sheng T. 
Published: June 2012

J. Neurochem. (2012) 122, 764–774.AbstractMicroglia are the ‘immune cells’ of the brain and their activation plays a vital role in the pathogenesis of many neurodegenerative diseases. Activated microglia produce high levels of pro‐inflammatory factors, such as TNFα, causing neurotoxicity. Here we show that vimentin played a key role in controlling microglia activation and neurotoxicity during cerebral ischemia. Deletion of vimentin expression significantly impaired microglia activation in response to LPS in vitro and transient focal cerebral ischemia in vivo. Reintroduction of the functional vimentin gene back into vimentin knockout microglia restored their response to LPS. More importantly, impairment of microglia activation significantly protected brain from cerebral ischemia‐induced neurotoxicity. Collectively, we demonstrate a previously unknown function of vimentin in controlling microglia activation.
Photoperiodic expression of two RALDH enzymes and the regulation of cell proliferation by retinoic acid in the rat hypothalamus
Authors: Shearer Kirsty D. , Stoney Patrick N. , Nanescu Sonia E. , Helfer Gisela , Barrett Perry , Ross Alexander W. , Morgan Peter J. , McCaffery Peter 
Published: June 2012

J. Neurochem. (2012) 122, 789–799.AbstractRetinoic acid (RA) has been found to regulate hypothalamic function, but precisely where it acts is unknown. This study shows expression of retinaldehyde dehydrogenase (RALDH) enzymes in tanycytes that line the third ventricle in an area overlapping with the site of hypothalamic neural stem cells. The influence of RA was examined on the proliferation of progenitors lining the third ventricle using organotypic slice cultures. As has been shown in other regions of neurogenesis, RA was found to inhibit proliferation. Investigations of the dynamics of RALDH1 expression in the rat hypothalamus have shown that this enzyme is in tanycytes under photoperiodic control with highest levels during long versus short days. In parallel to this shift in RA synthesis, cell proliferation in the third ventricle was found to be lowest during long days when RA was highest, implying that RALDH1 synthesized RA may regulate neural stem cell proliferation. A second RA synthesizing enzyme, RALDH2 was also present in tanycytes lining the third ventricle. In contrast to RALDH1, RALDH2 showed little change with photoperiodicity, but surprisingly the protein was present in the apparent absence of mRNA transcript and it is hypothesized that the endocytic tanycytes may take this enzyme up from the cerebrospinal fluid (CSF).
Investigating the utility of human embryonic stem cell‐derived neurons to model ageing and neurodegenerative disease using whole‐genome gene expression and splicing analysis
Authors: Patani Rickie , Lewis Patrick A. , Trabzuni Daniah , Puddifoot Clare A. , Wyllie David J. A. , Walker Robert , Smith Colin , Hardingham Giles E. , Weale Michael , Hardy John , Chandran Siddharthan , Ryten Mina 
Published: June 2012

J. Neurochem. (2012) 122, 738–751.AbstractA major goal in regenerative medicine is the predictable manipulation of human embryonic stem cells (hESCs) to defined cell fates that faithfully represent their somatic counterparts. Directed differentiation of hESCs into neuronal populations has galvanized much interest into their potential application in modelling neurodegenerative disease. However, neurodegenerative diseases are age‐related, and therefore establishing the maturational comparability of hESC‐derived neural derivatives is critical to generating accurate in vitro model systems. We address this issue by comparing genome‐wide, exon‐specific expression analyses of pluripotent hESCs, multipotent neural precursor cells and a terminally differentiated enriched neuronal population to expression data from post‐mortem foetal and adult human brain samples. We show that hESC‐derived neuronal cultures (using a midbrain differentiation protocol as a prototypic example of lineage restriction), while successful in generating physiologically functional neurons, are closer to foetal than adult human brain in terms of molecular maturation. These findings suggest that developmental stage has a more dominant influence on the cellular transcriptome than regional identity. In addition, we demonstrate that developmentally regulated gene splicing is common, and potentially a more sensitive measure of maturational state than gene expression profiling alone. In summary, this study highlights the value of genomic indices in refining and validating optimal cell populations appropriate for modelling ageing and neurodegeneration.
Involvement of dopaminergic neuronal cystatin C in neuronal injury‐induced microglial activation and neurotoxicity
Authors: Dutta Garima , Barber David S. , Zhang Ping , Doperalski Nicholas J. , Liu Bin 
Published: June 2012

J. Neurochem. (2012) 122, 752–763.AbstractFactors released from injured dopaminergic (DA) neurons may trigger microglial activation and set in motion a vicious cycle of neuronal injury and inflammation that fuels progressive DA neurodegeneration in Parkinson’s disease. In this study, using proteomic and immunoblotting analysis, we detected elevated levels of cystatin C in conditioned media (CM) from 1‐methyl‐4‐phenylpyridinium and dieldrin‐injured rat DA neuronal cells. Immunodepletion of cystatin C significantly reduced the ability of DA neuronal CM to induce activation of rat microglial cells as determined by up‐regulation of inducible nitric oxide synthase, production of free radicals and release of proinflammatory cytokines as well as activated microglia‐mediated DA neurotoxicity. Treatment of the cystatin C‐containing CM with enzymes that remove O‐ and sialic acid‐, but not N‐linked carbohydrate moieties markedly reduced the ability of the DA neuronal CM to activate microglia. Taken together, these results suggest that DA neuronal cystatin C plays a role in the neuronal injury‐induced microglial activation and neurotoxicity. These findings from the rat DA neuron‐microglia in vitro model may help guide continued investigation to define the precise role of cystatin C in the complex interplay among neurons and glia in the pathogenesis of Parkinson’s disease.
Ancient DNA identifies post‐glacial recolonisation, not recent bottlenecks, as the primary driver of contemporary mtDNA phylogeography and diversity in Scandinavian brown bears
Authors: Bray Sarah C.E. , Austin Jeremy J. , Metcalf Jessica L. , Østbye Kjartan , Østbye Eivind , Lauritzen Stein‐Erik , Aaris‐Sørensen Kim , Valdiosera Cristina , Adler Christina J , Cooper Alan 
Published: June 2012

AbstractAimBrown bear populations in Scandinavia show a strong mitochondrial DNA (mtDNA) phylogeographic structure and low diversity relative to other parts of Europe. Identifying the timing and origins of this mtDNA structure is important for conservation programs aimed at restoring populations to a natural state. Therefore, it is essential to identify whether contemporary genetic structure is linked to post‐glacial recolonisation from divergent source populations or an artefact of demographic impacts during recent population bottlenecks. We employed ancient DNA techniques to investigate the timing and potential causes of these patterns.LocationScandinavia and Europe.MethodsAncient mtDNA sequences from 20 post‐glacial Scandinavian bears were used to investigate phylogeographic structure and genetic diversity over the last 6000 years. MtDNA from 19 Holocene Norwegian bears was compared with 499 sequences from proximate extant populations in Sweden, Finland, Estonia and western Russia. A single mtDNA sequence from a Holocene Denmark sample was compared with 149 ancient and modern bears from Western Europe.ResultsAll nineteen Holocene Norwegian samples are identical to or closely related to the most common mtDNA haplotype found in northern Europe today. MtDNA diversity was low and not significantly different from extant populations in northern Europe. In Denmark, we identified a single mtDNA haplotype that is previously unrecorded from Scandinavia.Main conclusionsThe current discrete phylogeographic structure and lack of mtDNA diversity in Scandinavia is attributed to serial founder effects during post‐glacial recolonisation from divergent source populations rather than an artefact of recent anthropogenic impacts. In contrast to previous interpretations, the recolonisation of southern Scandinavia may not have been limited to bears from a single glacial refugium. Results highlight the importance of conserving the long‐term evolutionary separation between northern and southern populations and identify southern Scandinavia as an important reservoir of mtDNA diversity that is under threat in other parts of Europe.
Stable‐hydrogen isotope measures of natal dispersal reflect observed population declines in a threatened migratory songbird
Authors: Studds Colin E. , McFarland Kent P. , Aubry Yves , Rimmer Christopher C. , Hobson Keith A. , Marra Peter P. , Wassenaar Leonard I. 
Published: June 2012

AbstractAimMeasuring dispersal is crucial for estimating demographic rates that inform conservation plans for rare and threatened species. We evaluated natal dispersal patterns in Bicknell's thrush (Catharus bicknelli) across most of the breeding range using a 10‐year data set of stable‐hydrogen isotope ratios in feathers (δ2HF) grown on the natal area and sampled 1 year later at the first breeding site.LocationNorth‐eastern United States and south‐eastern Canada.MethodsWe used δ2HF values of adult thrushes sampled at 25 breeding sites as prior information for assigning first‐time breeders to their natal site. We calculated the minimum distance birds moved from their natal to first breeding site and fit these data to three statistical distributions for characterizing the importance of long‐distance dispersal: the exponential, Weibull and half‐Cauchy. Finally, we assessed differences in the probability of dispersal across the breeding range and through time to understand spatio‐temporal variation in demographic connectivity.ResultsThe δ2HF values of first‐time breeders were lower compared with those of adults, a difference that was greater at the southern compared with northern breeding range extreme. Assignment tests accounting for age differences in δ2HF suggested that most birds dispersed < 200 km from their natal area and within the centre of the breeding range, whereas comparatively few individuals dispersed up to 700 km. A Weibull distribution provided the best fit to these data. Two of three corrections for age differences in δ2HF indicated that natal dispersal probability declined by 30–38% from 1996 to 2005.Main conclusionsOur findings suggest that estimating natal dispersal with δ2HF measurements may contribute to understanding the resilience of geographically isolated Bicknell's thrush populations. Declining natal dispersal may be symptomatic of observed population declines and could compound this trend by limiting demographic exchange between habitat patches predicted to be increasingly isolated by natural and anthropogenic habitat changes.
The impact of aging on mitochondrial function and biogenesis pathways in skeletal muscle of sedentary high‐ and low‐functioning elderly individuals
Authors: Joseph Anna‐Maria , Adhihetty Peter J. , Buford Thomas W. , Wohlgemuth Stephanie E. , Lees Hazel A. , Nguyen Linda M.‐D. , Aranda Juan M. , Sandesara Bhanu D. , Pahor Marco , Manini Todd M. , Marzetti Emanuele , Leeuwenburgh Christiaan 
Published: June 2012

SummaryAge‐related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high‐ and low‐functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low‐functioning elderly (LFE) participants when compared to young and high‐functioning elderly participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in cytochrome c oxidase activity. Levels of key metabolic regulators, SIRT3 and PGC‐1α, were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects; however, no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population.
The use of multiple 8 compression suturing as a novel procedure to preserve fertility in patients with placenta accreta: case series
Authors: Shazly Sherif A.‐E.M. , Badee Ahmed Y.A. , Ali Mohammed K. 
Published: June 2012

Placenta accreta/percreta is a serious cause of intractable post‐partum haemorrhage during caesarean section and a common cause of peripartum hysterectomy. In this case series, we evaluated the use of multiple 8 sutures as a novel procedure to preserve the uterus in these cases. Seven women with placenta accreta/percreta were initially managed with bilateral uterine artery ligation. The procedure was resorted to in cases that did not respond to ligation (five women). Women were followed up for up to 24 months to report complications.
Implementation and audit of ‘Fast‐Track Surgery’ in gynaecological oncology surgery
Authors: Sidhu Verinder S. , Lancaster Letitia , Elliott David , Brand Alison H. 
Published: June 2012

BackgroundFast‐track surgery is a multidisciplinary approach to surgery that results in faster recovery from surgery and decreased length of stay (LOS).AimsThe aims of this study were as follows: (i) to report on the processes required for the introduction of fast‐track surgery to a gynaecological oncology unit and (ii) to report the results of a clinical audit conducted after the protocol's implementation.MethodsA fast‐track protocol, specific to our unit, was developed after a series of multidisciplinary meetings. The protocol, agreed upon by those involved in the care of women in our unit, was then introduced into clinical practice. An audit was conducted of all women undergoing laparotomy, with known or suspected malignancy. Information on LOS, complication and readmission rates was collected. Descriptive statistics and Poisson regression were used for statistical analysis.ResultsThe developed protocol involved a multidisciplinary approach to pre‐, intra‐ and postoperative care. The audit included 104 consecutive women over a 6‐month period, who were followed for 6 weeks postoperatively. The median LOS was 4 days. The readmission rate was 7% and the complication rate was 19% (1% intraoperative, 4% major and 14% minor). Multivariate analysis revealed that increased duration of surgery and increasing age were predictors of longer LOS.ConclusionThe development of a fast‐track protocol is achievable in a gynaecological oncology unit, with input from a multidisciplinary team. Effective implementation of the protocol can result in a short LOS, with acceptable complication and readmission rates when applied non‐selectively to gynaecological oncology patients.
Long‐Term Outcomes of Cardiovascular Implantable Electronic Devices in Patients with Staphylococcus aureus Bacteremia
Authors: OBEID KARAM M. , SZPUNAR SUSAN , KHATIB RIAD 
Published: June 2012

Background:

The use of cardiovascular implantable electronic devices (CIEDs) is increasing. Staphylococcus aureus bacteremia (SAB) poses a risk for hematogenous seeding of the device. Our aim is to identify risk factors associated with secondary CIED infection, due to hematogenous seeding, during SAB from an unrelated primary focus.
Methods:

All patients with SAB and CIED were screened. Patients with SAB due to a primary source unrelated to the CIED were included. Patients were classified into cases if CIED infection was documented and controls without CIED infection during a minimum of 12 weeks follow‐up. A retrospective review of patients’ charts was done.
Results:

Thirty patients with CIED and SAB from an unrelated focus were identified. CIED infection developed in 11 patients (36.7%). No significant differences were noted between cases and controls in the source, time‐to‐therapy, and time‐to‐intervene but infected devices were more likely to be implantable cardioverter‐defibrillators (ICD) versus permanent pacemakers (PPMs) (9/11 [81.8%] vs 2/11 [18.2%] respectively, crude odds ratio 12.6, 95% confidence interval 10.8–14.4; P = 0.003).
Conclusion:

Hematogenous seeding of a CIED during SAB from an unrelated focus is not uncommon. The risk factors for CIED seeding are unknown but ICD devices seem to be at greater risk when compared to PPM. The reasons are not yet clear. Larger studies are needed to better define risk factors and design preventive measures. (PACE 2012; 35:961–965)
Closed Loop Stimulation is Effective in Improving Heart Rate and Blood Pressure Response to Mental Stress: Report of a Single‐Chamber Pacemaker Study in Patients with Chronotropic Incompetent Atrial Fibrillation
Authors: PROIETTI RICCARDO , MANZONI GIANMAURO , DI BIASE LUIGI , CASTELNUOVO GIANLUCA , LOMBARDI LEONIDA , FUNDARÒ CAMILLA , VEGLIANTE NADIA , PIETRABISSA GIADA , SANTANGELI PASQUALE , CANBY ROBERT A. , SAGONE ANTONIO , VIECCA MAURIZIO , NATALE ANDREA 
Published: June 2012

Introduction:

Closed‐loop stimulation (CLS) is a form of rate‐adaptive pacing capable of providing an effective pacing rate profile not only during physical exercise but also during mental stress. To test its effectiveness, CLS and accelerometer sensor (AS) rate response were compared intraindividually during a mental stress test (MST).
Methods:

Thirty‐six patients (mean age 78.9 ± 6.4 years) implanted with a pacemaker with the CLS algorithm (Cylos, Biotronik, Berlin, Germany) underwent MSTs in different pacing configurations: nonrate‐adaptive mode (VVI), AS mode (VVIR), and CLS mode, respectively. A modified Stroop test was used in order to induce mental stress. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure, and pacing percentage burden were collected for 5 minutes before, during, and 5 minutes after the test.
Results:

Mean peak‐HR during MST was significantly higher in CLS configuration than in VVIR and VVI modes (92.8 ± 12.6 vs 78.9 ± 6.5 vs 77.8 ± 7.5; P ≤ 0.001). The average HR increase during MST was also higher in CLS configuration than in VVIR and VVI modes (22.7 ± 16.7 vs 8.2 ± 8.6 vs 6.6 ± 6.3; P ≤ 0.001). The percentage of pacing beats during MST was higher in CLS configuration than with the other two algorithms (48.4 ± 17.9 vs 27.4 ± 17.5 vs 25.8 ± 17.6; P ≤ 0.001). The average peak‐SBP was significantly higher during MST in CLS mode than in VVIR and VVI configurations (172.6 ± 15.5 vs 156.7 ± 12.2 vs 145.5 ± 13.7; P ≤ 0.001). The mean SBP increase showed a similar behavior (51.8 ± 24.7 vs 18.4 ± 13.7 vs 16.4 ± 10.3; P ≤ 0.001).
Conclusion:

CLS algorithm in a single‐chamber device is more effective than AS in detecting an hemodynamic demand due to an emotional stress and supplying a proper HR increase. These results are even more surprising compared to previous data in dual‐chamber pacemakers, because they imply that CLS algorithm can provide an appropriate rate‐modulation in patients with AF and chronotropic incompetence.
(PACE 2012; 35:990–998)