bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Histone Deacetylases as a Multifaceted Approach to Treat the Diverse Outcomes of Stroke
Authors: Langley Brett , Brochier Camille , Rivieccio Mark A.
Published: May 2009

Achieving therapeutic efficacy in ischemic stroke represents one of the biggest challenges in translational neurobiology. Despite extensive efforts, tissue plasminogen activator remains the only available intervention for enhancing functional recovery in humans once a stroke has occurred. To expand the repertoire of therapeutic options in stroke, one must consider and target its diverse pathophysiologies that trigger cell loss in a manner that also permits and enhances neuronal plasticity and repair. Several converging lines of inquiry suggest that histone deacetylase (HDAC) inhibition could be a strategy to achieve these goals. Here, we review evidence that targeting HDACs with low-molecular-weight inhibitors significantly decreases neuronal injury and improves functional outcome in multiple preclinical models of focal ischemia. These salutary effects emanate, in part, from modifications of chromatin and nonchromatin proteins that enhance adaptive gene expression or adaptive protein function. Together, the findings suggest that HDAC inhibition is a strategy capable of targeting diverse pathophysiologies of stroke with a wide therapeutic window.
Anticoagulation in Childhood-Onset Arterial Ischemic Stroke With Nonmoyamoya Arteriopathy
Authors: Bernard Timothy J. , Goldenberg Neil A. , Tripputi Mark , Manco-Johnson Marilyn J. , Niederstadt Thomas , Nowak-Göttl Ulrike
Published: May 2009

Background and Purpose—

Childhood arterial ischemic stroke treatment guidelines recommend extended anticoagulation in cardioembolism and dissection. We sought to investigate the safety of extended anticoagulation in childhood arterial ischemic stroke with nonmoyamoya arteriopathy, for which the risk of recurrent stroke is high.

Methods—

Thirty-seven patients with childhood-onset arterial ischemic stroke with acute arteriopathy (excluding moyamoya) were diagnosed between 1999 and 2007 and treated with anticoagulation for at least 4 weeks. Patients were followed in hospital-based cohort studies at 2 centers and systematically assessed for bleeding episodes and recurrent events.

Results—

Over a cumulative anticoagulation duration of 1329 patient-months, there were no major bleeding episodes and 2 clinically relevant bleeding episodes. Cumulative probability of recurrent arterial ischemic stroke at 1 year was 14%.

Conclusions—

Anticoagulation can be used safely for secondary arterial ischemic stroke prevention in children with acute nonmoyamoya arteriopathy. Anticoagulation is worthy of evaluation in future randomized, controlled treatment trials in this disease.
Relationship Between Blood Pressure Category and Incidence of Stroke and Myocardial Infarction in an Urban Japanese Population With and Without Chronic Kidney Disease
Authors: Kokubo Yoshihiro , Nakamura Satoko , Okamura Tomonori , Yoshimasa Yasunao , Makino Hisashi , Watanabe Makoto , Higashiyama Aya , Kamide Kei , Kawanishi Katsuyuki , Okayama Akira , Kawano Yuhei
Published: May 2009

Background and Purpose—

Chronic kidney disease (CKD) is increasingly recognized as an independent risk factor for stroke and myocardial infarction (MI). Few studies, however, have examined the relationship between blood pressure (BP) category and these diseases in subjects with and without CKD.

Methods—

We studied 5494 Japanese individuals (ages 30 to 79, without stroke or MI at baseline) who completed a baseline survey and received follow-up through December 2005. The glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease study equation modified by the Japanese coefficient. CKD was defined as an estimated GFR <60 mL/min/1.73m
2
. BP categories were defined by the European Society of Hypertension and European Society of Cardiology 2007 criteria.

Results—

In 64 395 person-years of follow-up, we documented 346 incidences of cardiovascular diseases (CVD; 213 strokes and 133 MI events). Compared with the GFR (≥90 mL/min/1.73m
2
) group, the hazard ratios (95% confidential intervals) for stroke were 1.9 (1.3 to 3.0) in the GFR 50 to 59 mL/min/1.73m
2
group and 2.2 (1.2 to 4.1) in the GFR <50 mL/min/1.73m
2
group. Results for cerebral infarction were similar. Compared with the optimal BP subjects without CKD, the normal BP, high-normal BP, and hypertensive subjects without CKD showed increased risks of CVD and stroke; however the impact of each BP category on CVD (
P
for interaction: 0.04 in men, 0.49 in women) and stroke (0.03 in men, 0.90 in women) was more evident in men with CKD.

Conclusions—

CKD may increase the association of BP and CVD in a Japanese urban population.
Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke
Authors: Lansberg Maarten G. , Bluhmki Erich , Thijs Vincent N.
Published: May 2009

Background and Purpose—

The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies.

Methods—

A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed.

Results—

The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.10 to 1.56;
P
=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43;
P
=0.83) compared to placebo treated patients.

Conclusions—

Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.
Petrus Brito, the author of the apparatus Ecce vicit leo?
Authors: Lefebvre-Teillard Anne
Published: May 2009

A comparison between the opinions attributed to Petrus Brito in the Paris glosses on the Compilatio prima and the opinions expressed in the apparatus Ecce vicit leo on the Decretum (with Animal est substantia, one of the two major representative apparatus of the French, and, specifically, Paris canonistic school of the 13th century) shows a substantial correspondence in several significant instances. It is therefore possible to attribute the authorship of Ecce vicit leo to Petrus Brito.
The editio stipulationis, An interpretation of D. 2,13,1,4 (Ulp. 4 ad ed.)
Authors: Babusiaux Ulrike
Published: May 2009

The Praetor's edict is said to be vague. Its contents are often better understood in the light of the broader context of legal and factual circumstances. Thus, the significance of the edict's editio stipulationis may be explained by analyzing its legal context and the practice with respect to the stipulatio, both of which establish that the stipulator was bound to inform the other party to the contract. That obligation may explain other specific features of the rules which applied to a verbal contract, in particular as regards the ambiguitas contra stipulatorem. An offence against the edictal obligation 'totam stipulationem edere' entailed that the stipulator would be worse off, but the sanction against him was not precisely stated. The very vague character of the edict may in this case have strengthened its effectiveness.
Authenticum and authenticae – What's in a name? References to Justinian's Novels in medieval manuscripts
Authors: Wallinga Tammo
Published: May 2009

In the Middle Ages Justinian's Novels were known in essentially two different forms: the Latin translation called the Authenticum, and excerpts from the Authenticum known as authenticae, which were incorporated in manuscripts of the Codex Justinianus. Correspondingly, there are two types of medieval references (allegationes): to texts in the Authenticum itself and to authenticae. This article studies the process of incorporating authenticae in the Codex Justinianus and argues that those allegationes that refer to the original Authenticum are no guarantee that this text was actually read in its original form by the author of the allegatio, rather than an authentica.
The Justices of the Peace at the heart of the French Law Reform experimental process (1914–1915)
Authors: Bernaudeau Vincent
Published: May 2009

The pre-enactment stages of the French Act of 22 December 1915 extending the cases where a review of judgements rendered by Justices of the Peace (at the canton-district level) could be brought before the Cour de Cassation shed a new light on the respective roles played by representatives of Parliament, of the central administration departments, and of the highest level of the Judiciary. These three categories of established public actors were brought together in an institutionalized Law Reform experimental process (laboratoire législatif), in which they shared a common legitimacy. An analysis of their work highlights the importance of their legal experience and knowledge for the conception and drafting of the Act, but is also necessary in order to interpret and understand those actors' notions with regard to the role of justice and the establishment of peace towards the citizens. The system and the rules which tend to ensure the Act's application emphasize the Executive Departments' capacity to affect the working of the courts, so as to implement their policies in favour of rationalizing the legal practitioners' work and modernizing the Judiciary at the beginning of the 20th century.
Extending the Life-Course Interdependence Model
Authors: Eitle David , Taylor John , Pih Kay Kei-ho
Published: May 2009

Few studies exploring the association between adolescent self-esteem and crime have considered whether the early adolescent self-esteem has any enduring consequences for young adult crime. Inspired by the life course and developmental criminology approaches, Arnett’s notion of emerging adulthood, and Kaplan’s self-derogation theory, this article examines whether self-derogation predicts young adult crime, controlling for early adolescent behaviors and more temporally proximate risk and protective factors. In addition, the article examines whether the strength of the ties to college and work exhibit interdependence with early self-derogation and young adolescent crime in predicting young adult crime. Using longitudinal data from a sample of males living in Miami-Dade County, the article finds that self-derogation predicts young adult crime. Furthermore, the authors find that early self-derogation exhibits interdependence with the bond to college, consistent with Wright, Caspi, Moffitt, and Silva’s social protection hypothesis, and that youth crime exhibits interdependence with the bond to work in young adulthood.
Safety and Biodistribution Profile of Placental-derived Mesenchymal Stromal Cells (PLX-PAD) Following Intramuscular Delivery
Authors: Ramot Yuval , Meiron Moran , Toren Amir , Steiner Michal , Nyska Abraham
Published: May 2009

The administration of mesenchymal stromal cells (MSCs) provides an exciting emerging therapeutic modality for the treatment of peripheral arterial disease, a condition that is associated with critical limb ischemia as its end stage. Placental-derived MSCs, termed PLX-PAD cells, are stable adhesive stromal cells isolated from full-term human placentae, cultured on carriers, and expanded in a bioreactor called the PluriX. These cells can be expanded in vitro without phenotypic or karyotypic changes. We studied the safety and biodistribution properties of PLX-PAD cells following intramuscular administration in NOD/SCID mice. No significant clinical signs, hematological and biochemical parameters, or major pathological changes were found in PLX-PAD-treated animals in comparison to vehicle controls. Several animals in the control and PLX-PAD-treated groups developed thymic malignant lymphoma, first seen after one month, as expected in this mouse strain. In addition, both groups developed spontaneous mesenteric vessel inflammation. Real-time quantitative polymerase chain reaction (RT-qPCR) demonstrated that distribution of PLX-PAD cells was confined to the injection site. Placental-derived MSCs remained in this site with gradual decrease in concentration during a three-month period. In view of these data, we conclude that the administration of PLX-PAD cells is not associated with any adverse effects in NOD/SCID mice.
The use of artificial nutrition among cancer patients enrolled in palliative home care services
Authors: Orrevall Y , Tishelman C , Permert J , Cederholm T
Published: May 2009

In this study, patients’ views and experiences of using home artificial nutrition, and factors associated with use of home parenteral nutrition (HPN) were investigated. Structured telephone interviews with 620 cancer patients enrolled in 21 palliative home care services were analysed. HPN was more common (11%) than home enteral tube feeding (HETF, 3%). Home artificial nutrition (including HPN and HETF) was usually introduced more than four months before death. Three of four HPN recipients also had oral food intake. HPN use was associated with eating difficulties, nausea/vomiting, and fatigue rather than gastrointestinal problems per se. HETF was generally used for patients with problems related to oesophagus and head and neck tumours. In conclusion the results suggest that, contrary to existing guidelines, HPN is used to supplement oral intake, and not only for patients with a non-functioning gastrointestinal tract.
An evaluation of the implementation of a programme to improve end-of-life care in nursing homes
Authors: Badger F , Clifford C , Hewison A , Thomas K
Published: May 2009

The Gold Standards Framework in Care Homes programme aims to improve the quality of end-of-life care for residents. The impact of introducing phase 2 of the programme to homes in England was evaluated. A pre–post survey design was adopted, focusing on indicators identified as markers of good end-of-life care. The 95 homes in phase 2 of the programme were invited to participate in the evaluation. Homes completed a baseline survey of care provision and an audit of the five most recent resident deaths. The survey and audit were repeated post programme completion. Forty-nine homes returned completed pre- and post-surveys, 44 returned pre- and post-data on deaths. Although some staff found completion of the programme challenging, homes that returned pre- and post-data demonstrated improvements in aspects of end-of-life care. There were statistically significant increases in the proportion of residents who died in the care homes and those who had an advanced care plan. Crisis admissions to hospital were significantly reduced. This evaluation indicates that appropriately funded structured programmes have the potential to assist nursing homes improve the provision of end-of-life care to older adults, in line with government health policy.
End-of-life care in hospital: a descriptive study of all inpatient deaths in 1 year
Authors: Abel J. , Rich A. , Griffin T. , Purdy S.
Published: May 2009

The objectives of this study are to ascertain how many patients who died in a district general hospital in England might have been able to be cared for at home, to obtain the cost of each inpatient stay, to make an estimate of the maximum resource implications of care packages for these patients, and to calculate the savings in hospital admissions that could be used for the development of community services. These objectives are dependant on full implementation of the End of Life Strategy. A descriptive study of all inpatient deaths in one year in a district general hospital in the south west of England was conducted. Data collection — case notes of all patients who died at the hospital from the beginning of June 2006 to end of May 2007. A total of 599 case notes of 627 patients who died in the study period were reviewed. A total of 331 patients (56%) were not assessed as being in the last year of life. Of the remaining 44%, 152 (26%) were clearly in the last year of life and 110 (18%) had significant co-morbidities and could probably have been recognised as being in the last year of life. A total of 399 (67%) of patients were appropriately admitted to hospital for their final illness, 194 (33%) could have been looked after at home. At least 119 (20%) clearly and 75 (13%) probably could have stayed at home. The mean cost of admission was £3173 per patient. A total of 77 (13%) of patients were admitted from nursing homes and 53 (69%) of these could have stayed in the nursing home to die. A total of 44% of all patients who died within the district general hospital had chronic life threatening illnesses. A maximum of one third of all hospital deaths could have been looked after at home if excellent end of life services were in place. When commissioning end of life care services, it is possible to calculate how many extra patients may need community care packages and the cost that could be redistributed from hospital to community for these services.
Psychiatrists’ use, knowledge and attitudes to first- and second-generation antipsychotic long-acting injections: comparisons over 5 years
Authors: Patel MX , Haddad PM , Chaudhry IB , McLoughlin S. , David AS
Published: May 2009

Psychiatrists’ attitudes and knowledge about antipsychotic long-acting injections (LAIs) are important given the increasing emphasis on patient choice in treatment and the availability of second-generation antipsychotic (SGA) LAIs. A cross-sectional study of consultant psychiatrists’ attitudes and knowledge in North West England was carried out. A pre-existing questionnaire on clinicians’ attitudes and knowledge regarding LAIs was updated. Of 102 participants, 50% reported a decrease in their use of LAIs. LAI prescribing was evenly split between first-generation antipsychotic (FGA) and SGA-LAIs. Most regarded LAIs as associated with better adherence (89%) than tablets. A substantial proportion believed that LAIs could not be used in first-episode psychosis (38%) and that patients always preferred tablets (33%). Compared with a previous sample, the current participants scored more favourably on a patient-centred attitude subscale (60.4% vs 63.5%, P = 0.034) and significantly fewer regarded LAIs as being stigmatising and old-fashioned. Reported LAI prescribing rates have decreased in the last 5 years despite an SGA-LAI becoming available and most clinicians regarding LAIs as effective. Most attitudes and knowledge have remained stable although concerns about stigma with LAI use have decreased. Concerns about patient acceptance continue as do negative views about some aspects of LAI use; these may compromise medication choices offered to patients.
Verapamil but not calpain or creatine alters arsenate-induced cardiac cell death
Authors: Luong MW , Rabkin SW
Published: May 2009

The objective of this study was to examine the potential of arsenate to induce cardiomyocyte cell death and to explore the cellular mechanisms of arsenate toxicity. Isolated cardiomyocytes in culture from embryonic chick hearts were treated with a pentavalent arsenic species (H3AsO4) or arsenate. Arsenate produced a significant ( P < 0.01) concentration-dependent increase in cell death with an EC50about 1 mM. Cardiomyocytes manifested a loss of actin structure, reduced size, and damaged nuclei. Creatine 0.1–100 uM did not significantly modify arsenate-induced cell death. In contrast, verapamil, 0.01–1 uM, produced a significant concentration-dependent accentuation of arsenate-induced cell death. The effect of verapamil was evident at low concentrations of arsenate, which produced only a small increase in cell death, and at high concentrations of arsenate, which induced a large amount of cell death. Verapamil alone did not alter cardiomyocyte cell death. By comparison, calpain inhibitor II did not modify arsenate-induced cardiomyocyte cell death. These data suggest that cardiomyocytes are vulnerable to the effects of verapamil to increase the cellular toxicity of arsenate. Two potential cellular mechanisms of arsenate toxicity, however, are likely not involved in arsenate toxicity namely calpain activation and reduction of creatine phosphate production.
Approach to Enteral Feeding in the PICU
Authors: Mehta Nilesh M.
Published: May 2009

The pediatric intensive care unit (PICU) environment poses unique challenges to achieving enteral nutrition (EN) goals for the critically ill child. Nutrition support in the PICU is often in conflict with the complexity of care provided to acutely ill children. A significant proportion of eligible patients do not receive optimal enteral nutrition for avoidable reasons. Early institution of EN is recommended and the gastric route is preferred because of ease of administration and reduced costs compared with the transpyloric route. In patients with poor gastric emptying or in cases where a trial of gastric feeding has failed, transpyloric or postpyloric feeding may be used to decrease the risk of aspiration and to improve enteral feed tolerance. However, there is no evidence of benefit for routine use of small bowel feeding in all patients admitted to the PICU. The placement of blind nasoenteric feeding tubes can be technically challenging, is not without complications, and requires local expertise and experience for successful placement and maintenance. A protocolized approach to selecting the optimal route and advancing enteral feedings may optimize EN delivery. Institutional practice guidelines based on consensus, available evidence, and national guidelines may decrease time to reaching caloric goal, improve protein balance, and potentially affect clinical outcomes. The rationale and challenges to the delivery and maintenance of optimal EN, and strategies to achieve optimal EN during critical illness, are discussed.
Enteral Nutrition Support of the Preterm Infant in the Neonatal Intensive Care Unit
Authors: Groh‐Wargo Sharon , Sapsford Amy
Published: May 2009

The delivery of a preterm baby is a nutrition emergency. Growth and the accumulation of nutrient reserves are higher during the third trimester of pregnancy than at any other time during the life cycle. Enteral nutrition is the preferred mode of support and human milk the preferred source of enteral nutrition. Human milk is highly digestible and contains many anti‐infective components, which confer a lower risk of infection. The mother of a preterm infant requires education, equipment, and encouragement to successfully initiate and sustain lactation. Human milk requires nutrient fortification to meet the protein and mineral needs of the rapidly growing preterm infant. Commercial human milk fortifiers are available. If human milk is unavailable or the volume is insufficient, preterm formulas are available. Preterm formulas have different sources of macronutrients and greater density of all nutrients than formulas intended for term newborns. Preterm infants benefit from early enteral feedings with slow but steady increases in feedings to achieve full support. Infants born at <35 weeks gestational age are supported with tube feedings. A transition to feedings at the breast or to bottle feedings is gradually made as the baby matures. Nutrient recommendations specific to the preterm infant are available. Special products and feeding strategies exist to respond to common medical conditions that can complicate nutrition management. Optimal nutrition care of the preterm infant offers the opportunity to improve outcomes for children.
A Review of Pharmacist Contributions to Diabetes Care in the United States
Authors: Armor Becky L. , Britton Mark L. , Dennis Vincent C. , Letassy Nancy A.
Published: May 2009

This paper summarizes the outcomes associated with pharmacist involvement in diabetes care in all pharmacy practice settings. Published literature was identified through a search of MEDLINE (1960 to September, week 1, 2008) and International Pharmaceutical Abstracts using the search terms “pharmacist,” “pharmaceutical care,” and “diabetes mellitus.” Only articles reporting clinical or behavior change outcomes were selected for review; papers written outside the United States and citations only in abstract form were not reviewed. The specific data extracted included the following: practice setting, model of care, roles of the pharmacist, study design, number of patients studied, duration of the evaluation, and documented outcomes such as changes in hemoglobin A1c values, adherence to standards of care (lipids, blood pressure, eye exams, foot exams, aspirin use), and changes in quality of life. The greatest improvements in hemoglobin A1c values tend to be observed when pharmacists work in collaborative practice models. Growing evidence demonstrates that pharmacists, working as educators, consultants, or clinicians in partnership with other health care professionals, are able to contribute to improved patient outcomes.
Research Dissemination and Diffusion
Authors: Kerner Jon F. , Hall Kara L.
Published: May 2009

In moving health and social service programs from planning into action, it is essential to understand the extent to which the knowledge gained from research should influence the actions taken by organizations and agencies that provide services (e.g., government, nongovernment organizations [NGOs]). The complexity of the challenges in translating lessons learned from science into different service settings, as well as into public policy, requires a multifaceted approach to accelerate the integration of research with practice. In this paper, the relationship between science and service is examined within the contexts of the scientific, health practice, and policy communities largely from a public sector perspective within the United States.
Divorce Attitudes Around the World
Authors: Toth Katalin , Kemmelmeier Markus
Published: May 2009

This article examines the link between culture and divorce attitudes using country-level data of the International Social Survey Programme 1994. Outside of examining the favorability of attitudes, we distinguish different types of attitudes based on whether the consequences of marital dissolution on children were considered when evaluating the acceptability of divorce. Testing competing hypotheses derived from attitude research and cross-cultural psychology, we demonstrate that (a) individualist societies exhibit more favorable divorce attitudes than collectivist societies but that (b) there is a curvilinear relationship between culture and type of divorce attitude, such that highly individualist and highly collectivist societies are similar with regard to the structure of prevailing divorce attitudes. The discussion focuses on the broader meanings of endorsing certain types of divorce attitudes in individualist and collectivist cultures.
Protective role of the HLA–A*02 allele in Portuguese patients with multiple sclerosis
Authors: Silva AM , Bettencourt A , Pereira C , Santos E , Carvalho C , Mendonça D , Costa PP , Monteiro L , Martins B
Published: May 2009

Background

Multiple sclerosis (MS) is associated with human leukocyte antigen (HLA) HLA–DRB1*15. Recent evidence that CD8 T cells are implicated in MS suggests that HLA class I may also contribute. An association of HLA–A*02 and A*03 alleles has been described.

Objectives

We examined the influence of HLA–A*02 and HLA–A*03 in Portuguese patients with MS, independently of HLA–DRB1*15 using a logistic regression model.

Conclusions

DRB1*15 increased the risk of developing MS and HLA–A*02 decreased the risk. A*03 had no effect. To analyze if HLA–A*02 association was independent from DRB1*15, an interaction between these two alleles was introduced in the model; no significant interaction was found.
Pathways Linking Intimate Partner Violence and Posttraumatic Disorder
Authors: Dutton Mary Ann
Published: May 2009

Intimate partner violence (IPV), which includes physical violence, sexual violence, and psychological or emotional abuse, is a significant public health threat. The Centers for Disease Control and Prevention (CDC) estimate that each year 1.5 million women are physically assaulted and/or raped by an intimate partner. However, because many victims of IPV are repeatedly abused, a more accurate accounting of the extent of violence suggests that approximately 4.8 million intimate partner physical assaults and rapes are perpetrated annually against women in the United States. The article discusses a survey involving 3,429 English-speaking women enrolled in a health maintenance organization (HMO) for 3 or more years. The findings are 46% of participants who were screened reported a lifetime history of any IPV and 14.7% reported a history within the past 5 years, including physical, sexual, and nonphysical types.
Review: Blood pressure and dementia — a comprehensive review
Authors: Kennelly Sean P. , Lawlor Brian A. , Kenny Rose Anne
Published: May 2009

Alzheimer's disease (AD) and vascular dementia (VaD) are important causes of cognitive decline in the elderly. As a result of an ageing population worldwide, the incidence of dementia is expected to rise exponentially over the coming decades. Vascular risk factors are implicated in the pathogenesis of both AD and VaD. Hypertension in midlife is particularly associated with an increased risk of developing dementia. One might hope the treatment of high blood pressure in midlife would reduce the risk of developing dementia, as it does the risk of stroke. Divergent results have been reported in studies examining this effect, with the evidence suggesting that certain antihypertensives confer benefits beyond others. This implies that certain drugs may have neuroprotective properties separate to their blood pressure lowering capabilities. Recent trials have added to our understanding of these relationships.
Clinical Implications of Peroneal Artery Variation
Authors: Kishman Lauren , Malin Danielle , Nerone Vince , Siesel Kathy
Published: May 2009

Vascular anatomy has a strong influence on the choice of surgical approach. Anomalies of vascular patterns may explain uncharacteristic physical or clinical findings. We present a case of an anomalous peroneal artery not previously described. The anomalous anatomic pattern is the peroneal artery replacing the posterior tibial artery in the medial ankle and providing the primary blood supply to the plantar foot.
Maternal Variables Influencing Duration of Breastfeeding Among Low-Income Mothers
Authors: McKechnie Anne Chevalier , Tluczek Audrey , Henriques Jeffrey B.
Published: May 2009

This study used a retrospective comparison of 2 naturally occurring groups, first to examine how exclusive versus partial breastfeeding relates to duration of breastfeeding and, second, to determine if factors such as age and body mass index are associated with exclusive versus partial breastfeeding duration. These factors were hypothesized to influence the amount of breastfeeding in a sample of 42 low-income mothers enrolled in the Supplemental Nutrition Program for Women, Infants, and Children of a predominately rural, Midwestern county. This study examined de-identified data from a state database spanning a calendar year. Breastfeeding behavior, age, and body mass index measurements for mothers giving birth within the first 6 months of that year were analyzed. Exclusive breastfeeding mothers breastfed longer, were of older age, and had lower body mass indexes than partial breastfeeding mothers. These findings further describe characteristics of low-income breastfeeding women. Understanding how factors associated with exclusive versus partial breastfeeding affect breastfeeding duration may inform clinicians and researchers of areas for future interventions.
Predictors of Weight and Adiposity During Early Infancy
Authors: Anderson Alex Kojo , Bignell Whitney , Buen Nicole , Chakraborty Priyanka , Anderson Mildred
Published: May 2009

The problem of overweight/ obesity among children has led some experts to suggest that the current Institute of Medicine recommendation for pregnancy weight gain may play a role in early childhood overweight. The study examined the predictors of early infancy weight and body composition as a prospective study that followed mothers and their newborns from birth through 12 weeks postpartum. Participants were 40 mother-infant pairs either exclusively breastfeeding or mixed feeding. The main outcomes were weight changes, weight-for-height z score, height-for-age z score, weight-for-age z score, BMI-for-age z score, and percent body fat measured by the PEA POD body composition system and adjusted for infant feeding practice and gestational age. Female infants accumulated higher percent body fat than male infants through the 12 weeks of follow-up. Maternal pregnancy weight gain positively correlated with infant length at the different time points and not infant weight. Maternal prepregnancy body mass index (P = .030) and pregnancy weight gain (P = .040) significantly correlated with infant birth weight and not weights at 2, 4, 8, and 12 weeks postpartum. Maternal pregnancy weight gain had an inverse association with infant percent body fat after adjusting for other covariates. In conclusion, maternal pregnancy weight gain predicted infant birth weight but not infant adiposity and subsequent weight through the first 12 weeks after delivery. Higher pregnancy weight gain predicts slower early postnatal growth.
Evaluation of Fruit Juice Intake and Body Mass Index Within a Sample of Ontario Preschoolers
Authors: Rysdale Lee A. , Brunelle Pamela L. , Simpson Janis Randall , Knee Christopher A. , Keller Heather H.
Published: May 2009

This study describes fruit juice consumption and associated factors for a sample of Ontario preschoolers and determines potential relationships between intake and body mass index (BMI). Secondary data analysis was conducted on growth, dietary, and demographic data collected during the validation of NutriSTEP (Nutrition Screening Tool for Every Preschooler) with 254 preschoolers, aged 3 to 5 years. Dietary data were collected through parent-completed 3-day food intake records. BMI was determined using child weight and height measurements taken by a registered dietitian. Demographic characteristics were gathered using an 8-item standardized questionnaire adapted from Statistics Canada. Bivariate analyses were performed to determine associations with juice intake, BMI category, and child, parental, and family characteristics. Almost one quarter (23.6%) of the preschoolers were at risk of being overweight or were overweight, 73.2% were within the normal range, and 3.1% were underweight. Overall, 88.1% of the children consumed 100% fruit juice during the intake period, with a mean intake of 210 ± 183.1 mL/d. Fifty-seven percent consumed more than 125 mL/d of fruit juice, and 31.1% consumed more than 250 mL/d, whereas US recommendations limit intake to 125 to 175 mL/d. No significant differences were seen in fruit juice intake among the BMI categories or with selected child, parental, or family characteristics. Consuming 100% fruit juice does not appear to be associated with preschoolers' BMI, but further longitudinal research is needed in larger, more diverse groups to confirm this finding. Meanwhile, increased parent education around appropriate beverage intake, including fruit juice, is warranted.
Transcriptomic analysis of tomato carpel development reveals alterations in ethylene and gibberellin synthesis during pat3/pat4 parthenocarpic fruit set
Authors: Pascual Laura , Blanca Jose M , Cañizares Joaquin , Nuez Fernado
Published: May 2009

Background

Tomato fruit set is a key process that has a great economic impact on crop production. We employed the Affymetrix GeneChip Tomato Genome Array to compare the transcriptome of a non-parthenocarpic line, UC82, with that of the parthenocarpic line RP75/59 (pat3/pat4mutant). We analyzed the transcriptome under normal conditions as well as with forced parthenocarpic development in RP75/59, emasculating the flowers 2 days before anthesis. This analysis helps to understand the fruit set in tomato.

Results

Differentially expressed genes were extracted with maSigPro, which is designed for the analysis of single and multiseries time course microarray experiments. 2842 genes showed changes throughout normal carpel development and fruit set. Most of them showed a change of expression at or after anthesis. The main differences between lines were concentrated at the anthesis stage. We found 758 genes differentially expressed in parthenocarpic fruit set. Among these genes we detected cell cycle-related genes that were still activated at anthesis in the parthenocarpic line, which shows the lack of arrest in the parthenocarpic line at anthesis. Key genes for the synthesis of gibberellins and ethylene, which were up-regulated in the parthenocarpic line were also detected.

Conclusion

Comparisons between array experiments determined that anthesis was the most different stage and the key point at which most of the genes were modulated. In the parthenocarpic line, anthesis seemed to be a short transitional stage to fruit set. In this line, the high GAs contends leads to the development of a parthenocarpic fruit, and ethylene may mimic pollination signals, inducing auxin synthesis in the ovary and the development of a jelly fruit.
Inter-observer reproducibility of HER2 immunohistochemical assessment and concordance with fluorescent in situhybridization (FISH): pathologist assessment compared to quantitative image analysis
Authors: Turashvili Gulisa , Leung Samuel , Turbin Dmitry , Montgomery Kelli , Gilks Blake , West Rob , Carrier Melinda , Huntsman David , Aparicio Samuel
Published: May 2009

Background

In breast cancer patients, HER2 overexpression is routinely assessed by immunohistochemistry (IHC) and equivocal cases are subject to fluorescentin situhybridization (FISH). Our study compares HER2 scoring by histopathologists with automated quantitation of staining, and determines the concordance of IHC scores with FISH results.

Methods

A tissue microarray was constructed from 1,212 invasive breast carcinoma cases with linked treatment and outcome information. IHC slides were semi-quantitatively scored by two independent pathologists on a range of 0 to 3+, and also analyzed with an Ariol automated system by two operators. 616 cases were scorable by both IHC and FISH.

Results

Using data from unequivocal positive (3+) or negative (0, 1+) results, both visual and automated scores were highly consistent: there was excellent concordance between two pathologists (kappa = 1.000, 95% CI: 1-1), between two machines (kappa = 1.000, 95% CI: 1-1), and between both visual and both machine scores (kappa = 0.898, 95% CI: 0.775–0.979). Two pathologists successfully distinguished negative, positive and equivocal cases (kappa = 0.929, 95% CI: 0.909–0.946), with excellent agreement with machine 1 scores (kappa = 0.835, 95% CI: 0.806–0.862; kappa = 0.837, 95% CI: 0.81–0.862), and good agreement with machine 2 scores (kappa = 0.698, 95% CI: 0.6723–0.723; kappa = 0.709, 95% CI: 0.684–0.732), whereas the two machines showed good agreement (kappa = 0.806, 95% CI: 0.785–0.826). When comparing categorized IHC scores and FISH results, the agreement was excellent for visual 1 (kappa = 0.814, 95% CI: 0.768–0.856), good for visual 2 (kappa = 0.763, 95% CI: 0.712–0.81) and machine 1 (kappa = 0.665, 95% CI: 0.609–0.718), and moderate for machine 2 (kappa = 0.535, 95% CI: 0.485–0.584).

Conclusion

A fully automated image analysis system run by an experienced operator can provide results consistent with visual HER2 scoring. Further development of such systems will likely improve the accuracy of detection and categorization of membranous staining, making this technique suitable for use in quality assurance programs and eventually in clinical practice.
Dynamic regulation of RNA editing of ion channels and receptors in the mammalian nervous system
Authors: Tan Bao Zhen , Huang Hua , Lam Runyi , Soong Tuck Wah
Published: May 2009

The post-transcriptional modification of mammalian transcripts in the central nervous system by adenosine-to-inosine RNA editing is an important mechanism for the generation of molecular diversity, and serves to regulate protein function through recoding of genomic information. As the molecular players and an increasing number of edited targets are identified and characterized, adenosine-to-inosine modification serves as an exquisite mechanism for customizing channel function within diverse biological niches. Here, we review the mechanisms that could regulate adenosine-to-inosine RNA editing and the impact of dysregulation in clinical conditions.
RAGE: therapeutic target and biomarker of the inflammatory response—the evidence mounts
Authors: Ramasamy Ravichandran , Yan Shi Fang , Schmidt Ann Marie
Published: May 2009

RAGE may be a biomarker and/or target for therapeutic intervention in chronic disease such as diabetes, inflammation, neurodegeneration, and tumors.

The RAGE binds multiple ligand families linked to hyperglycemia, aging, inflammation, neurodegeneration, and cancer. Activation of RAGE by its ligands stimulates diverse signaling cascades. The recent observation that the cytoplasmic domain of RAGE interacts with diaphanous or mDia–1 links RAGE signal transduction to cellular migration and activation of the Rho GTPases, cdc42 and rac–1. Pharmacological blockade of RAGE or genetic deletion of RAGE imparts significant protection in murine models of diabetes, inflammatory conditions, Alzheimer’s disease, and tumors. Intriguingly, soluble forms of RAGE, including the splice variant–derived esRAGE, circulate in human plasma. Studies in human subjects suggest that sRAGE levels may be modulated by the diseases impacted by RAGE and its ligands. Thus, in addition to being a potential therapeutic target in chronic disease, monitoring of plasma sRAGE levels may provide a novel biomarker platform for tracking chronic inflammatory diseases, their severity, and response to therapeutic intervention.
Age at onset of first episode and time to treatment in
in-patients with bipolar disorder
Authors: Morken Gunnar , Vaaler Arne E. , Folden Gunn E. , Andreassen Ole A. , Malt Ulrik F.
Published: May 2009

This study aimed to investigate the relationship between age at onset and
time to first pharmacological treatment in patients with either bipolar I
or II disorder. A total of 146 consecutive in-patients acutely admitted
from the same catchment area were included. Patients were divided into
four age groups: 0–12 years (23%); 13–18 years (32%); 19–29 years (26%);
and 30 years (18%). Mean age at first affective episode was 20.2 years
(s.d.=11.8). This represents a similar pattern to the age at onset seen
in out-patients in the USA. Early age at onset predicted a longer time to
first pharmacological treatment (ρ =0.695, P
<0.01).
Prevalence of autism-spectrum conditions: UK school-based
population study
Authors: Baron-Cohen Simon , Scott Fiona J. , Allison Carrie , Williams Joanna , Bolton Patrick , Matthews Fiona E. , Brayne Carol
Published: May 2009

Background

Recent reports estimate the prevalence of autism-spectrum conditions in
the UK to be 1%.

Aims

To use different methods to estimate the prevalence of autism-spectrum
conditions, including previously undiagnosed cases, in
Cambridgeshire.

Method

We carried out a survey of autism-spectrum conditions using the Special
Educational Needs (SEN) register. A diagnosis survey was distributed to
participating schools to be handed out to parents of all children aged
5–9 years. The mainstream primary school population was screened for
unknown cases.

Results

The prevalence estimates generated from the SEN register and diagnosis
survey were 94 per 10 000 and 99 per 10 000 respectively. A total of 11
children received a research diagnosis of an autism-spectrum condition
following screening and assessment. The ratio of known:unknown cases is
about 3:2 (following statistical weighting procedures). Taken together,
we estimate the prevalence to be 157 per 10 000, including previously
undiagnosed cases.

Conclusions

This study has implications for planning diagnostic, social and health
services.
Prenatally Induced Changes in Muscle Structure and Metabolic Function Facilitate Exercise-Induced Obesity Prevention
Authors: Huber Korinna , Miles Jennifer L. , Norman Amy M. , Thompson Nichola M. , Davison Michael , Breier Bernhard H.
Published: May 2009

Effective regulation of energy metabolism is vital for the maintenance of optimal health, and an inability to make these dynamic adjustments is a recognized cause of obesity and metabolic disorders. Epidemiological and experimental studies have highlighted the role of prenatal factors in the disease process, and it is now generally accepted that maternal nutrition during pregnancy significantly influences intrauterine development, shaping postnatal health. Consequences of impaired nutrition during fetal development include intrauterine growth restriction (IUGR) and subsequent obesity development in adult life. We have previously shown that prenatal undernutrition has a lasting effect on behavior, with IUGR offspring expressing a higher preference for voluntary exercise, and moderate daily exercise preventing obesity development. The present study investigated skeletal muscle structure in IUGR offspring and how moderate daily exercise drives changes in metabolic pathways that promote obesity prevention. Pregnant Wistar rats were either fed chow ad libitum or undernourished, generating control or IUGR offspring respectively. Although red muscle structure indicated higher oxidative capacity in IUGR offspring, obesity prevention was not due to increased fatty acid oxidation, indicated by decreased peroxisomal proliferator-activated receptor-γ coactivator 1 and carnitine-palmitoyltransferase 1 expression. In contrast, increased protein kinase Cζ expression and glycogen content in white muscle of exercised IUGR offspring suggests an enhanced capacity for anaerobic utilization of glucose. Furthermore, exercise-induced lactate accumulation was effectively prevented by stimulation of a lactate shuttle, driven by the increases in monocarboxylate transporters-4 and -1 in white muscle. This enhanced metabolic flexibility in IUGR offspring may facilitate muscle contractile performance and therefore support moderate daily exercise for effective obesity prevention.