bluuebunny/crossref_metadata_2025 huggingface dataset:
Alzheimer′s disease and granulocyte density diversity
Authors: Järemo Petter , Milovanovic Micha , Buller Caroline , Nilsson Staffan , Winblad Bengt
Published: March 2013

Background

The current study investigates circulating eosinophils and neutrophils in Alzheimer′s (AD) type dementia with respect to density (kg/L). The existence of β‐amyloid plaques in the brain is a feature of AD. Sporadic scientific reports indicate that the disease affects circulating neutrophils. In contrast, numerous publications investigate inflammatory reactions in AD brains. Locally, the plaques evoke a substantial inflammatory response involving activated microglia and astrocytes.

Methods

Subjects with probable AD (n = 39) were included and compared with elderly individuals (n = 22) lacking apparent memory problems. We sampled 10 mL venous blood in citrate. Granulocytes were separated according to density in linear Percoll™ gradients. Subsequently, the gradients were divided into density subfractions (n = 16). In every fraction, determination of eosinophil and neutrophil counts was carried out.

Results

AD sufferers displayed less granulocytes in fractions nos. 13‐15 containing light cells. For these fractions, the P‐values proved to be (P < 0·001; not significant; P = 0·03) and (P = 0·01; P = 0·01; not significant), for eosinophils and neutrophils, respectively.

Conclusions

The present work describes that less circulating light granulocytes are a feature of AD demented individuals. It is to hypothesize that it is a sign of impaired granulocyte turnover and cell damage. It is concluded that AD affects inflammatory cells in the periphery and that the behaviour of granulocytes in dementia is worthwhile further studies.
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

Axonal 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

Mutations 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.
The mdx mouse model as a surrogate forDuchenne muscular dystrophy
Authors: Partridge Terence A.
Published: March 2013

Research into fundamental principles and the testing of therapeutic hypotheses for treatment of human disease is commonly performed on mouse models of human diseases. Although this is often the only practicable approach, it carries a number of caveats arising from differences between the two species. This review focuses on the example of skeletal muscle disease, in particular muscular dystrophy, to identify some of the principal classes of obstacles to translation of data from mouse to humans. Of these, the difference in scale is one of the most commonly ignored, and is of particular interest because it has quite major repercussions for evaluation of some classes of intervention and of outcome criteria, while having comparatively little bearing on others. Likewise, inter‐species differences and similarities in cell and molecular biological mechanisms underlying development, growth and response to pathological processes should be considered on an individual basis. An awareness of such distinctions is crucial if we are to avoid misjudging the likely applicability to humans of results obtained on mouse models.
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

Joint 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

PEGylation 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

Type 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.
ECONOMIC FREEDOM AND INCOME INEQUALITY REVISITED: EVIDENCE FROM A PANEL ERROR CORRECTION MODEL
Authors: APERGIS NICHOLAS , DINCER OGUZHAN , PAYNE JAMES E.
Published: March 2013

We investigate the causal relationship between income inequality and economic freedom using data from U.S. states over the period 1981 to 2004 within a panel error correction model framework. The results indicate bidirectional causality between income inequality and economic freedom in both the short and the long run. These results suggest that high income inequality may cause states to implement redistributive policies causing economic freedom to decline. As economic freedom declines, income inequality rises even more. In other words, it is quite possible for a state to get caught in a vicious circle of high income inequality and heavy redistribution. (JEL D63, H11)
Resource tracking in marine parasites: going with the flow?
Authors: Thompson Ross M. , Poulin Robert , Mouritsen Kim N. , Thieltges David W.
Published: March 2013

Understanding how diversity interacts with energy supply is of broad ecological interest. Most studies to date have investigated patterns within trophic levels, reflecting a lack of food webs which include information on energy flow. We added parasites to a published marine energy‐flow food web, to explore whether parasite diversity is correlated with energy flow to host taxa. Parasite diversity was high with 36 parasite taxa affecting 40 of the 51 animal taxa. Adding parasites increased the number of trophic links per species, trophic link strength, connectance, and food chain lengths. There was evidence of an asymptotic relationship between energy flowing through a food chain and parasite diversity, although there were clear outliers. High parasite diversity was associated with host taxa which were highly connected within the food web. This suggests that energy flow through a taxon may favour parasite diversity, up to a maximal value. The evolutionary and energetic basis for that limitation is of key interest in understanding the basis for parasite diversity in natural food webs and thus their role in food web dynamics.
No free lunch: displaced marsh consumers regulate a prey subsidy to an estuarine consumer
Authors: Boucek Ross E. , Rehage Jennifer S.
Published: March 2013

Pulse subsidies account for a substantial proportion of resource availability in many systems, having persistent and cascading effects on consumer population dynamics, and energy flow within and across ecosystem boundaries. Although the importance of pulsed resource subsidies is well‐established, the mechanisms that regulate resource fluxes across ecosystem boundaries are not well understood. The aim of our study was to determine the extent that marsh consumers regulated a marsh prey subsidy to estuarine consumers in the oligohaline reaches of an Everglades estuary. We characterized a marsh pulsed subsidy of cyprinodontoid, invertebrate and sunfish prey that move into the upper estuary from adjacent drying marshes. In response to the prey pulse, we examined the numerical, fitness and dietary responses of three focal consumers in the upper estuary; two marsh species (largemouth bass and bowfin) that accompanied the subsidy as a result of marsh drying, and one estuarine consumer (snook). At the onset of marsh drying and the prey subsidy, estuarine consumers switched diets to consume the larger marsh prey (sunfishes), while bass and bowfin maintained similar diets (cyprinodontoids and invertebrates respectively) than pre and post subsidy. From the consumption of this subsidy, bass (marsh species) and snook (estuarine species) exhibited fitness gains while bowfin did not. Although both marsh and estuarine consumers benefitted from the subsidy, we found evidence that freshwater consumers shunted some of the subsidy away from snook. Of the prey sampled in consumer stomachs, 41% of marsh prey biomass was eaten by marsh consumers, while 59% was consumed by the estuarine consumer. We conclude that the amount of the marsh prey available to estuarine consumers may be greater in the absence of marsh consumers, thus the magnitude of the prey subsidy could depend on the dynamics of the marsh consumers from donor communities.
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

The 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

Using 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 Applications

The 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

Objectives

To 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.

Design

Development phase: variable selection and rating by clinician panel. Validation phase: medical record review and secondary data analysis.

Setting

Assessing the Care of Vulnerable Elders‐2 study.

Participants

Six hundred forty‐four older (≥75) individuals receiving ambulatory care.

Measures

Development: 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.

Results

The 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).

Conclusion

Older 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

Objectives

To identify older adults with comorbidities or poor functional status at high risk of postoperative venous thromboembolism (VTE).

Design

Retrospective cohort study.

Setting

Veterans Affairs Medical Center (VAMC).

Participants

Older adults who underwent total hip and knee replacement (THR and TKR) from 2002 to 2009.

Measurements

Using 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.

Results

There 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).

Conclusion

Individuals 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

Objectives

To evaluate the relative contributions of basal and prandial components to total hyperglycemia in older and younger adults with type 2 diabetes mellitus.

Design

Participant‐level data were pooled from six randomized studies of 24 weeks or longer treatment with insulin glargine or an active comparator.

Setting

Prospective, randomized Phase 3 or 4 controlled trials.

Participants

One thousand six hundred ninety‐nine individuals: 509 (30%) aged 65 and older and 1,190 (70%) younger than 65.

Measurements

Contributions 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.

Results

After 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).

Conclusion

The 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.
Resynchronization: Considering Device‐Based Cardiac Therapy in Older Adults
Authors: Kramer Daniel B. , Reynolds Matthew R. , Mitchell Susan L.
Published: March 2013

Cardiac resynchronization therapy (CRT) is a device‐based treatment available to select individuals with systolic heart failure (HF), a large proportion of whom are aged 65 and older. As the field of CRT advances, together with shifting demographics and expanded indications for implantation, there is a need for practitioners caring for older adults to understand what is and is not known about the use of CRT specifically in this population. Clinical trials demonstrating benefits for severe and mild HF have uncertain generalizability to older adults. Other studies demonstrate that device‐related complications may be more common with CRT than with simpler devices and more common in older adults. CRT clinical trials also may not adequately capture outcomes and concerns specific to older adults, including quality of life and end‐of‐life care experiences. Informed decision‐making by clinicians, policy‐makers, and patients will require greater understanding of the use and outcomes of CRT in older persons.
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

Background

A 4‐year‐old rhesus macaque presented with acute, progressive paresis of the extremities.

Methods

A complete blood count, serum biochemical analysis, neurologic exam and necropsy were performed.

Results

The clinical, histopathological, and immunohistochemical findings confirmed a high‐grade intramedullary glial tumor of the spinal cord that was most consistent with an ependymoma.

Conclusions

We describe a case of a naturally occurring spontaneous spinal cord neoplasia in a non‐human primate.
Rural Chile Transformed: Lights and Shadows
Authors: Bengoa José
Published: March 2013

Rural society in Chile has undergone profound change over the past few decades. For centuries, large haciendas had dominated Chile's Central Valley. The agrarian reforms carried out by Frei and Allende – and to a greater extent the counter‐reform of Pinochet – transformed that property structure with its generalized system of agricultural production for the domestic market. Recently, there has been a marked shift in emphasis towards specialization, exports and off‐farm agricultural resources. A seasonal labour market has arisen, employing predominantly female workers, whose precarious work conditions stand in marked contrast to the success of Chilean agricultural exports. This paper reviews the main trends in Chilean agriculture and rural society, drawing on data gathered principally in Colchagua Province, which is known for its fine export wines.
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

Ischemia/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.
Pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats
Authors: Pypendop B. H. , Brosnan R. J. , Majewski‐Tiedeken C. R. , Stanley S. D. , Ilkiw J. E.
Published: March 2013

The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End‐tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 μg/kg), alfentanil (100 μg/kg), or sufentanil (1 μg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration–time data. A 3‐compartment model best fitted the concentration–time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady‐state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo‐SD (range)], and the terminal half‐life (min) [median (range)] were 0.25 ± 0.04 (0.09–0.34), 2.18 ± 0.16 (1.79–2.83), 18.6 ± 5.0 (15–29.8), and 151 (115–211) for fentanyl; 0.10 ± 0.01 (0.07–0.14), 0.89 ± 0.16 (0.68–1.83), 11.6 ± 2.6 (9.2–15.8), and 144 (118–501) for alfentanil; and 0.06 ± 0.01 (0.04–0.10), 0.77 ± 0.07 (0.63–0.99), 17.6 ± 4.3 (13.9–24.3), and 54 (46–76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half‐lives for fentanyl and alfentanil, longer than for sufentanil.
Plasma and tissue pharmacokinetics of marbofloxacin in experimentally infected chickens with Mycoplasma gallisepticum and Escherichia coli
Authors: Ding H. , Wang L. , Shen X. , Gu X. , Zeng D. , Zeng Z.
Published: March 2013

The plasma and tissue pharmacokinetics of marbofloxacin in chickens experimentally infected with Mycoplasma gallisepticum and Escherichia coli were studied. Marbofloxacin was given to 66 infected chickens by oral administration at a dosage of 5 mg/kg b.w., once a day for three days. Plasma, brain, kidney, liver, lung, muscle and trachea were collected and marbofloxacin concentrations were analyzed by a high performance liquid chromatography method. In the infected chickens, maximal marbofloxacin concentrations in plasma, brain, kidney, liver, lung, muscle and trachea were 1.84, 1.33, 7.35, 5.61, 3.12, 2.98, and 4.51 g/mL (g); the elimination half‐lives of marbofloxacin were 6.8, 2.74, 9.31, 8.45, 9.55, 11.53 and 5.46 h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. AUC were calculated to be 9.68, 8.04, 45.1, 27.03, 20.56, 19.47, and 32.68 μg/mL (g) ·h for plasma, brain, kidney, liver, lung, muscle and trachea, respectively. Marbofloxacin concentration in tissues except for brain exceeded marbofloxacin concentration in plasma, with AUCtissue/AUCplasma ranging from 2.01 to 4.66 and Peaktissue/Peakplasma ranging from 1.62 to 3.99. The results showed that a marbofloxacin dosage of 5 mg/kg administered orally at 24 h intervals may provide successful treatment of chicken with MG and E. coli infection.
Prevalence and causes of abnormal liver function in patients with coeliac disease
Authors: Casella Giovanni , Antonelli Elisabetta , Di Bella Camillo , Villanacci Vincenzo , Fanini Lucia , Baldini Vittorio , Bassotti Gabrio
Published: March 2013

Background & Aims

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten‐free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten‐free diet.

Patients and methods

Data from 245 untreated CD patients (196 women and 49 men, age range 15–80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed.

Results

Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten‐free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis.

Conclusions

In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications.
Facultative predation and scavenging by mammalian carnivores: seasonal, regional and intra‐guild comparisons
Authors: Pereira Laura M. , Owen-Smith Norman , Moleón Marcos
Published: March 2013

The extent to which vertebrate carnivores shift facultatively between predation and scavenging has recently been emphasized. Potentially, all carnivores have to do is wait until animals succumb to the debilitating effects of advancing age. However, this may be insufficient because of intense competition among other scavengers and decomposers for food. Moreover, the availability of carcasses of animals dying from causes other than predation varies seasonally, so carnivores must be adapted to exploit various sources of food through the seasonal cycle.

We explore how mammalian carnivores cope with seasonality in carrion supply and in prey vulnerability to predation. We focus mainly on large carnivores and ungulates, and compare especially ecological communities in northern temperate and African savanna ecosystems.

When carrion is scarce, carnivores can (i) take advantage of temporarily vulnerable segments of prey populations, such as newborn young, heavily pregnant females and males distracted or debilitated by reproduction, (ii) switch to carcass remains left by or stolen from other carnivores, or (iii) exploit small animals and non‐animal food sources.

Relationships between carnivores tending towards predation or scavenging can be both competitive and facilitative. Top carnivores may provide a supply of carcasses throughout the year, which subsidizes scavengers when carrion availability from other sources is low. Alterations of seasonal patterns due to anthropogenic environmental change may enhance the role of top carnivores as buffers of anthropogenic perturbations of natural processes.

Megaherbivores, which are not normally regarded as prey but can provide huge carrion subsidies, may strongly influence interspecific interactions between carnivores and the proportion of food flowing towards scavenging relative to predation.

Relationships among carnivores based on hunting vs. scavenging strategies are flexible and subject to changes in response to circumstances. Their functional complexity is relevant for assessing the effects of global change on ecosystem function.
Numerical modeling of asteroid survivability and possible scenarios for the Morokweng crater‐forming impact
Authors: Potter Ross W. K. , Collins Gareth S.
Published: March 2013

The fate of the impactor is an important aspect of the impact‐cratering process. Defining impactor material as surviving if it remains solid (i.e., does not melt or vaporize) during crater formation, previous numerical modeling and experiments have shown that survivability decreases with increasing impact velocity, impact angle (with respect to the horizontal), and target density. Here, we show that in addition to these, impactor survivability depends on the porosity and shape of the impactor. Increasing impactor porosity decreases impactor survivability, while prolate‐shaped (polar axis > equatorial axis) impactors survive impact more so than spherical and oblate‐shaped (polar axis < equatorial axis) impactors. These results are used to produce a relatively simple equation, which can be used to estimate the impactor fraction shocked to a given pressure as a function of these parameters. By applying our findings to the Morokweng crater‐forming impact, we suggest impact scenarios that explain the high meteoritic content and presence of unmolten fossil meteorites within the Morokweng crater. In addition to previous suggestions of a low‐velocity and/or high‐angled impact, this work suggests that an elongated and/or low porosity impactor may also help explain the anomalously high survivability of the Morokweng impactor.
Thermal modeling of shock melts in Martian meteorites: Implications for preserving Martian atmospheric signatures and crystallization of high‐pressure minerals from shock melts
Authors: Shaw Cliff S. J. , Walton Erin
Published: March 2013

The distribution of shock melts in four shergottites, having both vein and pocket geometry, has been defined and the conductive cooling time over the range 2500 °C to 900 °C calculated. Isolated 1 mm2 pockets cool in 1.17 s and cooling times increase with pocket area. An isolated vein 1 × 7 mm in Northwest Africa (NWA) 4797 cools to 900 °C in 4.5 s. Interference between thermal haloes of closely spaced shock melts decreases the thermal gradient, extending cooling times by a factor of 1.4 to 100. This is long enough to allow differential diffusion of Ar and Xe from the melt. Small pockets (1 mm2) lose 2.2% Ar and 5.2% Xe during cooling, resulting in a small change in the Ar/Xe ratio of the dissolved gas over that originally trapped. With longer cooling times there is significant fractionation of Xe from Ar and the Ar/Xe ratio increases rapidly. The largest pockets show less variation of Ar/Xe and likely preserve the original trapped gas composition. Considering all of the model calculations, even the smallest isolated pockets have cooling times greater than the duration of the pressure pulse, i.e., >0.01 s. The crystallization products of these shock melts will be unrelated to the peak shock pressure experienced by the meteorite.
Microevolution in time and space: SNP analysis of historical DNA reveals dynamic signatures of selection in Atlantic cod
Authors: Therkildsen Nina O. , Hemmer‐Hansen Jakob , Als Thomas D. , Swain Douglas P. , Morgan M. Joanne , Trippel Edward A. , Palumbi Stephen R. , Meldrup Dorte , Nielsen Einar E.
Published: March 2013

Little is known about how quickly natural populations adapt to changes in their environment and how temporal and spatial variation in selection pressures interact to shape patterns of genetic diversity. We here address these issues with a series of genome scans in four overfished populations of Atlantic cod (Gadus morhua) studied over an 80‐year period. Screening of >1000 gene‐associated single‐nucleotide polymorphisms (SNPs) identified 77 loci that showed highly elevated levels of differentiation, likely as an effect of directional selection, in either time, space or both. Exploratory analysis suggested that temporal allele frequency shifts at certain loci may correlate with local temperature variation and with life history changes suggested to be fisheries induced. Interestingly, however, largely nonoverlapping sets of loci were temporal outliers in the different populations and outliers from the 1928 to 1960 period showed almost complete stability during later decades. The contrasting microevolutionary trajectories among populations resulted in sequential shifts in spatial outliers, with no locus maintaining elevated spatial differentiation throughout the study period. Simulations of migration coupled with observations of temporally stable spatial structure at neutral loci suggest that population replacement or gene flow alone could not explain all the observed allele frequency variation. Thus, the genetic changes are likely to at least partly be driven by highly dynamic temporally and spatially varying selection. These findings have important implications for our understanding of local adaptation and evolutionary potential in high gene flow organisms and underscore the need to carefully consider all dimensions of biocomplexity for evolutionarily sustainable management.
Esophageal motor responses to increasing adjustment of an implanted gastric band
Authors: Burgerhart J. S. , Aarts E. O. , van de Meeberg P. C. , Berends F. J. , Siersema P. D. , Smout A. J. P. M.
Published: March 2013

Background

The adjustable gastric band is an effective surgical treatment to induce weight loss in patients with morbid obesity. We aimed to assess the effects of band placement and stepwise adjustment on esophageal motility, using high‐resolution manometry (HRM).

Methods

Patients underwent esophageal HRM before and 6 weeks after gastric band placement. During postoperative assessment, HRM was combined with intraband pressure measurement at increasing filling volumes.

Key Results

In total, 15 patients were studied. Mean DCI (±SD) decreased from 1085.3 ± 1064.1 mmHg s−1 cm−1 before to 507 ± 347.2 mmHg s−1 cm−1 (P = 0.015) after band placement, mean IBP from 10.7 ± 1.7 mmHg to 7.7 ± 1.6 mmHg (P = 0.01). Stepwise band adjustment from 1 to 8 mL had an immediate and profound effect on swallow‐induced esophageal contractions: DCI increased from 766 ± 590.4 to 7231 ± 6298.1 mmHg s−1 cm−1, IBP from 4.3 mmHg to 31.1 ± 17.3 mmHg, and intraband pressure increased from −109.1 ± 60.6 mmHg to 150.2 ± 65 mmHg. During band filling with volumes >5 mL, upward displacement of the LES was observed, indicative of shortening of the esophagus; the distance between the UES and LES decreased from 23.5 ± 1.3 cm at 0 mL to 19.9 ± 2 cm at 8 mL.

Conclusions & Inferences

Stepwise gastric band adjustment leads to immediate enforcement of esophageal peristalsis associated with an increase in intrabolus pressure and with pronounced esophageal shortening. Subjects who lack these responses to outflow obstruction may be more prone to dysphagia after band placement.
Fungal community analysis by high‐throughput sequencing of amplified markers – a user's guide
Authors: Lindahl Björn D. , Nilsson R. Henrik , Tedersoo Leho , Abarenkov Kessy , Carlsen Tor , Kjøller Rasmus , Kõljalg Urmas , Pennanen Taina , Rosendahl Søren , Stenlid Jan , Kauserud Håvard
Published: March 2013

Novel high‐throughput sequencing methods outperform earlier approaches in terms of resolution and magnitude. They enable identification and relative quantification of community members and offer new insights into fungal community ecology. These methods are currently taking over as the primary tool to assess fungal communities of plant‐associated endophytes, pathogens, and mycorrhizal symbionts, as well as free‐living saprotrophs.

Taking advantage of the collective experience of six research groups, we here review the different stages involved in fungal community analysis, from field sampling via laboratory procedures to bioinformatics and data interpretation. We discuss potential pitfalls, alternatives, and solutions.

Highlighted topics are challenges involved in: obtaining representative DNA/RNA samples and replicates that encompass the targeted variation in community composition, selection of marker regions and primers, options for amplification and multiplexing, handling of sequencing errors, and taxonomic identification.

Without awareness of methodological biases, limitations of markers, and bioinformatics challenges, large‐scale sequencing projects risk yielding artificial results and misleading conclusions.