bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality of life in haemophilia A: Hemophilia Utilization Group Study Va (HUGS‐Va)
Authors: POON J.‐L. , ZHOU Z.‐Y. , DOCTOR J. N. , WU J. , ULLMAN M. M. , ROSS C. , RISKE B. , PARISH K. L. , LOU M. , KOERPER M. A. , GWADRY‐SRIDHAR F. , FORSBERG A. D. , CURTIS R. G. , JOHNSON K. A.
Published: April 2012

Summary.  This study describes health‐related quality of life (HRQoL) of persons with haemophilia A in the United States (US) and determines associations between self‐reported joint pain, motion limitation and clinically evaluated joint range of motion (ROM), and between HRQoL and ROM. As part of a 2‐year cohort study, we collected baseline HRQoL using the SF‐12 (adults) and PedsQL (children), along with self‐ratings of joint pain and motion limitation, in persons with factor VIII deficiency recruited from six Haemophilia Treatment Centres (HTCs) in geographically diverse regions of the US. Clinically measured joint ROM measurements were collected from medical charts of a subset of participants. Adults (N = 156, mean age: 33.5 ± 12.6 years) had mean physical and mental component scores of 43.4 ± 10.7 and 50.9 ± 10.1, respectively. Children (N = 164, mean age: 9.7 ± 4.5 years) had mean total PedsQL, physical functioning, and psychosocial health scores of 85.9 ± 13.8, 89.5 ± 15.2, and 84.1 ± 15.3, respectively. Persons with more severe haemophilia and higher self‐reported joint pain and motion limitation had poorer scores, particularly in the physical aspects of HRQoL. In adults, significant correlations (P < 0.01) were found between ROM measures and both self‐reported measures. Except among those with severe disease, children and adults with haemophilia have HRQoL scores comparable with those of the healthy US population. The physical aspects of HRQoL in both adults and children with haemophilia A in the US decrease with increasing severity of illness. However, scores for mental aspects of HRQoL do not differ between severity groups. These findings are comparable with those from studies in European and Canadian haemophilia populations.
Marked differences in CCR5 expression and activation levels in two South African populations
Authors: Picton Anabela C. P. , Shalekoff Sharon , Paximadis Maria , Tiemessen Caroline T.
Published: April 2012

The chemokine receptor CCR5 is pivotal in determining an individual’s susceptibility to HIV‐1 infection and rate of disease progression. To establish whether population‐based differences exist in cell surface expression of CCR5 we evaluated the extent of CCR5 expression across all peripheral blood cell types in individuals from two populations, South African Africans (SAA) and South African Caucasians (SAC). Significant differences in CCR5 expression, both in number of CCR5 molecules per cell (density) and the percentage of CCR5‐expressing cells, were observed between the two study groups, within all cell subsets. Most notably, the percentage of all CCR5+ cell subsets was significantly lower in SAC compared with SAA individuals (P < 0·01) among natural killer (NK) ‐cell subsets (CD56+, CD16+ CD56+ and CD56dim) whereas CCR5 density was significantly higher in SAC compared with SAA individuals in CCR5+ CD8+ T‐cell subsets and CCR5+ NK‐cell subsets (CD56+, CD16+ CD56+ and CD56dim) (all P < 0·05). These relationships were maintained after exclusion of CCR5Δ32 heterozygous individuals (n = 7) from the SAC dataset. The SAA individuals exhibited significantly higher cell activation levels, as measured by HLA‐DR expression, than SAC individuals in CD4+ T‐cell subsets (P = 0·002) and CD56+ NK‐cell subsets (P < 0·001). This study serves to demonstrate that ethnically divergent populations show marked differences in both cell activation and CCR5 expression, which are likely to impact on both susceptibility to HIV‐1 infection and the rate of HIV‐1 disease progression.
An in vitro assessment of the physical properties of novel Hyflex nickel–titanium rotary instruments
Authors: Peters O. A. , Gluskin A. K. , Weiss R. A. , Han J. T.
Published: April 2012

Peters OA, Gluskin AK, Weiss RA, Han JT. An in vitro assessment of the physical properties of novel Hyflex nickel–titanium rotary instruments. International Endodontic Journal, 45, 1027–1034, 2012.

Aim  To determine several properties including torsional and fatigue limits, as well as torque during canal preparation, of Hyflex, a rotary instrument manufactured from so‐called controlled memory nickel–titanium alloy.

Methodology  The instruments were tested in vitro using a special torque bench that permits both stationary torque tests according to ISO3630‐1 and fatigue limit determination, as well as measurement of torque (in Ncm) and apical force (in N) during canal preparation. Fatigue limit (in numbers of cycles to failure) was determined in a 90°, 5 mm radius block‐and‐rod assembly. Simulated canals in plastic blocks were prepared using both a manufacturer‐recommended single‐length technique as well as a generic crown‐down approach. anova with Bonferroni post hoc procedures was used for statistical analysis.

Results  Torque at failure ranged from 0.47 to 1.38 Ncm, with significant differences between instrument sizes (P < 0.0001). Fatigue life ranged from 260 to 2565, with the shortest and longest lifespan for instruments size 20, .04 taper and size 25, .08 taper, respectively. Torque during canal preparation was significantly higher for small instruments used in the single‐length technique but lower for the size 40, .04 taper, compared to a crown‐down approach. No instrument fractured; 82% of the instruments used were plastically deformed; however, only 37% of these remained deformed after a sterilization cycle.

Conclusions  Hyflex rotary instruments are bendable and flexible and have similar torsional resistance compared to instruments made of conventional NiTi. Fatigue resistance is much higher, and torque during preparation is less, compared to other rotary instruments tested previously under similar conditions.
Less than eight (and a half) misconceptions of spatial analysis
Authors: Kühn Ingolf , Dormann Carsten F.
Published: April 2012

Spatial analyses are indispensable analytical tools in biogeography and macroecology. In a recent Guest Editorial, Hawkins (Journal of Biogeography, 2012, 39, 1–9) raised several issues related to spatial analyses. While we concur with some points, we here clarify those confounding (1) spatial trends and spatial autocorrelation, and (2) spatial autocorrelation in the response variable and in the residuals. We argue that recognizing spatial autocorrelation in statistical modelling is not only a crucial step in model diagnostics, but that disregarding it is essentially wrong.
Morphopathological features of a severe ulcerative disease outbreak associated with Tenacibaculum maritimum in cultivated sole, Solea senegalensis (L.)
Authors: Vilar P , Faílde L D , Bermúdez R , Vigliano F , Riaza A , Silva R , Santos Y , Quiroga M I
Published: April 2012

This study describes morphopathologic changes in naturally infected farmed Senegalese sole affected by tenacibaculosis caused by Tenacibaculum maritimum. Macroscopic observation, in addition to light microscopy and scanning electron microscopy, was used to study the lesions. Main lesions were characterized by complete loss of epidermis and dermis, as well as extensive necrosis of muscle layers. Mild‐to‐moderate inflammatory response with the presence of macrophages was noted around hyaline degenerated muscle cells. Gram‐negative filamentous bacteria could be detected only at the dermis. Under scanning electron microscopy, filamentous bacteria located over the scales without epithelium could be observed. These findings together with the isolation and PCR detection of the bacteria in kidney and skin tissues suggest that once the bacteria reach the dermis, probably through eroded epidermis, they are able to proliferate and produce enzymes that are responsible for the damage in the underlying tissues.
Occlusal dysesthesia: a qualitative systematic review of the epidemiology, aetiology and management
Authors: HARA E. S. , MATSUKA Y. , MINAKUCHI H. , CLARK G. T. , KUBOKI T.
Published: April 2012

Summary  Occlusal dysesthesia refers to a persistent complaint of uncomfortable bite sensation with no obvious occlusal discrepancy. This systematic review aimed to draw a picture of such patients, to present an agreement of previously reported diagnostic criteria and to analyse the evidence level of the recommended management approaches. An electronic search for all relevant reports on occlusal dysesthesia was thoroughly performed based on previous nomenclatures (e.g. phantom bite, occlusal hyperawareness) in PubMed and The Cochrane Library in July, 2011. A total of 84 reports were matched, among which only 11 studies were included after a two‐step (abstract and detailed full‐text revision) screening process. Additionally, a thorough manual review of reference lists of the included reports enabled the inclusion of two additional studies. Data analysis revealed that 37 occlusal dysesthesia patients presented a mean age of 51·7 ± 10·6 years and were predominantly women (male/female: 1/5·1) with symptom duration of more than 6 years (average: 6·3 ± 7·5 years) and with concomitant psychological disturbances (e.g. mood disorders, somatoform disorders, personality disorders). Only four authors presented diagnostic criteria for occlusal dysesthesia, which served as the basis for an agreement in the diagnostic criteria. Treatment approaches included psychotherapy, cognitive/behaviour therapy, splint therapy and prescription of anti‐depressants or anti‐anxiety drugs. Classification of evidence level of management approaches, however, revealed that most of them were expert opinions with single‐ or multiple‐case report(s). Future studies are necessary for a deeper understanding of the mechanisms behind the occlusal dysesthesia symptoms, and consequently, for improvements in evidence‐based management approaches.
Perceived chewing ability and need for long‐term care in the elderly: a 5‐year follow‐up study
Authors: MORIYA S. , TEI K. , MURATA A. , MURAMATSU M. , INOUE N. , MIURA H.
Published: April 2012

Summary  Increasing need for long‐term care in older adults is expected with the ageing of Japan’s population. The aim of the present study was to show the relationship between perceived chewing ability and long‐term care needs for over 5 years in elderly persons. The chewing ability of 812 elderly persons living independently was evaluated at baseline using self‐assessed masticatory ability, and it was classified into one of three categories: ability to chew all foods (good masticatory ability), ability to chew only slightly hard food (fair masticatory ability), and ability to only chew soft or pureed food (poor masticatory ability). Participants’ care needs were then followed through Japan’s long‐term care insurance system for over 5 years. The log‐rank test and Cox proportional hazard model were used to examine statistical differences in the frequency of care‐needs certification between participants with good and fair or poor masticatory ability. Among participants aged 65–79 years, the frequency of care‐needs certification was significantly higher in those with fair or poor masticatory ability than in those with good masticatory ability, and the relative hazard ratio was significantly higher in those with fair or poor masticatory ability than in those with good masticatory ability, after adjusting for age, gender, current employment status, educational background, social interaction, chronic medical conditions and dentition status. These relationships were not found among those aged 80–93 years. Impairment in perceived chewing ability may be associated with higher incidence of certification in Japan’s long‐term care insurance system among elderly persons aged 65–79.
Sleep bruxism increases the risk for painful temporomandibular disorder, depression and non‐specific physical symptoms
Authors: FERNANDES G. , FRANCO A. L. , SIQUEIRA J. T. T. , GONÇALVES D. A. G. , CAMPARIS C. M.
Published: April 2012

Summary  To explore the relationship between sleep bruxism (SB), painful temporomandibular disorders (TMD) and psychologic status in a cross‐sectional study. The sample consisted of 272 individuals. The Research Diagnostic Criteria for TMD (RDC/TMD) was used to diagnose TMD; SB was diagnosed by clinical criteria proposed by The American Academy of Sleep Medicine. The sample was divided into four groups: (1) patients without painful TMD and without SB, (2) patients without painful TMD and with SB, (3) patients with painful TMD and without SB and (4) patients with painful TMD and with SB. Data were analysed by Odds Ratio test with a 95% confidence interval. Patients with SB had an increased risk for the occurrence of myofascial pain (OR = 5·93, 95% CI: 3·19–11·02) and arthralgia (2·34, 1·58–3·46). Group 3 had an increased risk for moderate/severe depression and non‐specific physical symptoms (10·1, 3·67–27·79; 14·7, 5·39–39·92, respectively), and this risk increased in the presence of SB (25·0, 9·65–64·77; 35·8, 13·94–91·90, respectively). SB seems to be a risk factor for painful TMD, and this in turn is a risk factor for the occurrence of higher depression and non‐specific physical symptoms levels, but a cause–effect relationship could not be established.
Iophenoxic acid as a bait marker for wild mammals: efficacy and safety considerations
Authors: Ballesteros Cristina , Sage Mickaël , Fisher Penny , Massei Giovanna , Mateo Rafael , De La Fuente José , Rossi Sophie , Gortázar Christian
Published: April 2012

Bait delivery of vaccines, toxicants or contraceptives to target wild mammals is an essential component of management strategies worldwide. Marking agents are required to enable the identification of individuals that consume the baits in order to evaluate and optimize the cost‐efficacy of baiting campaigns.

Ethyl‐iophenoxic acid (Et‐IPA) is an organic iodine‐containing compound that has been used increasingly since the 1980s as a bait marker. It binds to proteins in animal blood and therefore can be detected indirectly by measuring plasma or serum iodine concentration or directly by measuring plasma or serum Et‐IPA concentration with liquid chromatography. Methyl‐iophenoxic acid and propyl‐iophenoxic acid can also be used to provide quantitative information on temporal or spatial patterns of bait consumption in a range of mammalian species. We review the suitability of Et‐IPA and its analogues as bait markers in mammals.

The highly variable persistence of analogues and in species highlights the need for calibration testing of each compound as a marker for each species and for each proposed use before starting a bait delivery trial.

After absorption, the fate of IPAs (by metabolism, distribution and excretion) is variable, but most are bound to plasma proteins. Marking efficacy is therefore high.

The implications of exposure to IPAs for predators and humans were analyzed to evaluate its safety for delivery to wild mammals. Although it is highly unlikely that secondary exposure through ingestion could involve sufficiently large quantities to produce adverse effects, further studies are necessary to assess long‐term effects after chronic exposure to these compounds.

IPAs can mark animal serum for long periods of time, and improvements in detection methods for them are currently being developed, so that they are a good choice for oral baiting field experiments with mammals.
Behind every great ant, there is a great gut
Authors: POULSEN MICHAEL , SAPOUNTZIS PANAGIOTIS
Published: April 2012

Ants are quite possibly the most successful insects on Earth, with an estimated 10 000 species worldwide, making up at least a third of the global insect biomass, and comprising several times the biomass of all land vertebrates combined. Ant species have diverse trophic habits, including herbivory, hunting/gathering, scavenging and predation and are distributed in diverse habitats, performing a variety of important ecosystem functions. Often they exert these functions while engaging in symbiotic associations with other insects, plants or microbes; however, remarkably little work has focused on the potential contribution of the ants’ gut symbionts. This issue of Molecular Ecology contains a study by Anderson et al. (2012), who take a comparative approach to explore the link between trophic levels and ant microbiomes, specifically, to address three main questions: (i) Do closely related herbivorous ants share similar bacterial communities? (ii) Do species of predatory ants share similar bacterial communities? (iii) Do distantly related herbivorous ants tend to share similar bacterial communities? By doing so, the authors demonstrate that ants with similar trophic habits appear to have relatively conserved gut microbiomes, suggesting symbiont functions that directly relate to dietary preference of the ant host. These findings suggest an ecological role of gut symbionts in ants, for example, in metabolism and/or protection, and the comparative approach taken supports a model of co‐evolution between ant species and specific core symbiont microbiomes. This study, thereby, highlights the omnipresence and importance of gut symbioses—also in the Hymenoptera—and suggests that these hitherto overlooked microbes likely have contributed to the ecological success of the ants.
Pilot study of a pharmaceutical care intervention in an outpatient lung transplant clinic
Authors: Harrison Jennifer J. , Wang June , Cervenko Julia , Jackson Leah , Munyal Dipika , Hamandi Bassem , Chernenko Susan , Dorosz Josie , Chaparro Cecilia , Singer Lianne G.
Published: April 2012

Background

Lung transplant recipients have complex drug regimens. Study objectives were to assess drug therapy problems (DTPs), pharmacist recommendations, and patient satisfaction with pharmacist services.

Methods

Using a pharmaceutical care assessment process, pharmacists identified DTPs and made therapeutic recommendations. Number of DTPs identified per pharmacist visit was calculated and compared to standard care visits through retrospective chart review. Potential clinical impact of recommendations was evaluated by blinded clinicians. Patient satisfaction was assessed via survey.

Results

Fifty‐five DTPs were identified in 43 patients over 50 pharmacist visits (1.05 ± 1.34 DTPs per visit). In these same patients, rate of DTP identification was 0.51 ± 0.64 DTPs per standard visit in the preceding two‐wk period (p = 0.018 vs. pharmacist visit). The most common DTPs identified by the pharmacist were adverse drug effect (27%) and untreated indication (25%). Overall, 62% of pharmacist recommendations were rated very significant or significant. Survey return rate was 58% and satisfaction scores ranged from 3 to 5 out of 5. Review of medications and teaching regarding the use of medications received the most “very satisfied” and “highly important” scores.

Conclusions

Pharmacists can make valuable contributions in a lung transplant clinic setting by identifying DTPs and making recommendations with a positive impact on patient outcomes and satisfaction.
Ten‐yr renal allograft survival of patients with antiphospholipid antibody syndrome
Authors: Vaidya Smita
Published: April 2012

Background

Long‐term allograft survival of antiphospholipid antibody syndrome (APAS) patients as well as patients who have antiphospholipid antibodies but no thrombotic complications remains largely unknown. This study evaluates long‐term allograft survival of APA as well as patients with APAS.

Methods

During the study period from January 1, 1992 through May 31, 2009, 1625 patients with ESRD awaiting renal transplants were screened for APAS. Ninety‐four (5.8%) of these patients had circulating levels of anticardiolipin antibodies (ACA) and 39 of these patients had documented evidence of clotting disorders and were diagnosed with APAS. Twenty‐one patients with APAS received transplants on either low molecular weight (LMW) heparin or Coumadin as anticoagulation therapy. Of 94 patients with only ACA, 46 received renal transplants. Of the remaining 1492 patients, 1285 patients with no evidence of either ACA or APAS received renal transplants.

Results

Ten‐yr allograft survival of patients with APAS treated with Coumadin was similar to those treated with LMW heparin (18% vs. 20%, NS). However, those allograft survivals were significantly lower than those patients positive for ACA (28%) alone (ACA vs. LMW heparin or Coumadin p = 0.0001).

Conclusion

Despite anticoagulation therapies, patients with APAS have lower long‐term graft survival than those patients who have circulating ACA but no APAS.
Treatment options for acute depression in bipolar disorder
Authors: Bauer Michael , Ritter Philipp , Grunze Heinz , Pfennig Andrea
Published: April 2012

Bauer M, Ritter P, Grunze H, Pfennig A. Treatment options for acute depression in bipolar disorder. Bipolar Disord 2012: 14 (Suppl. 2): 37–50. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S.

Objective:  The burden of depression represents the most debilitating dimension for the majority of patients with bipolar disorder and dominates the long‐term course of the illness. The purpose of this manuscript is to review the evidence base of the available treatment options for bipolar depression within two frequent clinical scenarios.

Methods:  The evidence is largely based on a systematic literature search and appraisal that was part of the development of the German Guideline for Bipolar Disorders. All relevant randomized controlled trials were critically evaluated.

Results:  Overall, the number of suitably controlled studies for the treatment of bipolar depression is relatively low. There are two common scenarios. Scenario A, if a patient with bipolar depression is currently not being treated with a mood‐stabilizing agent (de novo depression, first or subsequent episode), then quetiapine or olanzapine are options, or alternatively, carbamazepine and lamotrigine can be considered. Antidepressants are an option for short‐term use, but whether they are best administered as monotherapy or in combination with mood‐stabilizing agents is still controversial. In practice, most clinicians use antidepressants in combination with an antimanic agent. Scenario B, if a patient is already being treated optimally with a mood‐stabilizing agent (good adherence and appropriate dose) such as lithium, lamotrigine is an option. There is no evidence for additional benefit from antidepressants where a patient is already being treated with a mood stabilizer; however, in practice an antidepressant is often trialled. Efficient psychotherapy is an important part of the treatment regimen and should span all phases of the illness.

Conclusions:  Treatment decisions in bipolar depression involve a range of different pharmacological and non‐pharmacological options. Monitoring potential unwanted effects and the appropriateness of treatment can help to effectively balance benefits and risks in individual situations. However, the quality of the assessment and reporting of risks in clinical trials need to be improved to better inform treatment decisions.
Protective effects of cathelicidin‐encoding Lactococcus lactis in murine ulcerative colitis
Authors: Wong Clover Ching Man , Zhang Lin , Li Zhe Jie , Wu Willium Ka Kei , Ren Shun Xiang , Chen Yang Chao , Ng Tzi Bun , Cho Chi Hin
Published: April 2012

Background and Aim:  Intrarectal administration of mouse cathelin‐related antimicrobial peptide (mCRAMP) reduced intestinal inflammation in mice. In the current study, we examined whether mCRAMP‐transformed Lactococcus lactis given orally attained similar protective effects.

Method:  mCRAMP was produced and secreted from the transformed L. lactis. Murine colitis was induced by ingestion of 3% dextran sulfate sodium (DSS) for 7 days. Eight or 10 log colony forming unit (cfu) L. lactis or the transformed strains with or without nisin induction were given orally as a parallel treatment with DSS. The body weight, fecal microbiota populations, clinical symptoms and histological examinations of colonic tissues were determined. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) level were also evaluated to reflect the degree of inflammation. A prototype anti‐inflammatory drug sulfasalazine was used as a reference drug to compare the efficacy and mechanisms of action for ulcerative colitis (UC).

Result:  Compared with the control group with colitis, cathelicidin‐transformed L. lactis could improve the clinical symptoms, maintain crypt integrity and preserve mucus content (P < 0.01). The number of apoptotic cells, MPO activity and MDA level were also significantly reduced (P < 0.05). The increases of fecal microbiota in colitis animals were markedly prevented (P < 0.001). Unlike mCRAMP‐encoding L. lactis, effective doses of sulfasalazine only alleviated the clinical symptoms (P < 0.01) but not the mucosal damage in the colon.

Conclusion:  mCRAMP‐transformed L. lactis has been shown to produce mCRAMP, effectively preventing murine UC. Oral administration of this biological preparation is better than sulfasalazine for the treatment of UC.
UNIQUE USAGE OF A PARTIALLY COVERED METAL STENT FOR DRAINAGE OF A PANCREATIC PSEUDOCYST VIA ENDOSONOGRAPHY‐GUIDED TRANSCYSTGASTROSTOMY
Authors: NICI ANTHONY J. , HUSSAIN SYED A. , KIM SANG H. , MEHTA PREETI
Published: April 2012

Pancreatic pseudocysts are frequent complications of pancreatitis episodes. The current therapeutic modalities for drainage of pancreatic pseudocysts include surgical, percutaneous, and endoscopic drainage modalities. Endosonography‐assisted endoscopic drainage of these pseudocysts with the placement of multiple plastic or fully covered self‐expanding biliary metal stents is becoming more commonly carried out. The present case report discusses the unique and successful drainage of a pancreatic pseudocyst with the placement of a partially covered self‐expanding metal stent.
Comparative review of family–professional communication: What mental health care can learn from oncology and nursing home care
Authors: van de Bovenkamp Hester M. , Trappenburg Margo J.
Published: April 2012

Because family members take on caring tasks and also suffer as a consequence of the illness of the patient, communication between health‐care professionals and family members of the patient is important. This review compares communication practices between these two parties in three different parts of health care: oncology, nursing home care, and mental health care. It shows that there are important differences between sectors. Mental health stands out because contacts between family members and professionals are considered problematic due to the autonomy and confidentiality of the patient. The article explores several explanations for this, and, by comparing the three health sectors, distils lessons to improve the relationship between family members and health‐care professionals.
Ampakine CX546 increases proliferation and neuronal differentiation in subventricular zone stem/progenitor cell cultures
Authors: Schitine Clarissa , Xapelli Sara , Agasse Fabienne , Sardà‐Arroyo Laura , Silva Ana P. , De Melo Reis Ricardo A. , de Mello Fernando G. , Malva João O.
Published: April 2012

Ampakines are chemical compounds known to modulate the properties of ionotropic α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA)‐subtype glutamate receptors. The functional effects attributed to ampakines involve plasticity and the increase in synaptic efficiency of neuronal circuits, a process that may be intimately associated with differentiation of newborn neurons. The subventricular zone (SVZ) is the main neurogenic niche of the brain, containing neural stem cells with brain repair potential. Accordingly, the identification of new pharmaceutical compounds with neurogenesis‐enhancing properties is important as a tool to promote neuronal replacement based on the use of SVZ cells. The purpose of the present paper is to examine the possible proneurogenic effects of ampakine CX546 in cell cultures derived from the SVZ of early postnatal mice. We observed that CX546 (50 μm) treatment triggered an increase in proliferation, evaluated by BrdU incorporation assay, in the neuroblast lineage. Moreover, by using a cell viability assay (TUNEL) we found that, in contrast to AMPA, CX546 did not cause cell death. Also, both AMPA and CX546 stimulated neuronal differentiation as evaluated morphologically through neuronal nuclear protein (NeuN) immunocytochemistry and functionally by single‐cell calcium imaging. Accordingly, short exposure to CX546 increased axonogenesis, as determined by the number and length of tau‐positive axons co‐labelled for the phosphorylated form of SAPK/JNK (P‐JNK), and dendritogenesis (MAP2‐positive neurites). Altogether, this study shows that ampakine CX546 promotes neurogenesis in SVZ cell cultures and thereby may have potential for future stem cell‐based therapies.
Climate‐driven diversity dynamics in plants and plant‐feeding insects
Authors: Nyman Tommi , Linder Hans Peter , Peña Carlos , Malm Tobias , Wahlberg Niklas
Published: April 2012

Ecology Letters(2012)

The origin of species‐rich insect–plant food webs has traditionally been explained by diversifying antagonistic coevolution between plant defences and herbivore counter‐defences. However, recent studies combining paleoclimatic reconstructions with time‐calibrated phylogenies suggest that variation in global climate determines the distribution, abundance and diversity of plant clades and, hence, indirectly influences the balance between speciation and extinction in associated herbivore groups. Extant insect communities tend to be richest on common plant species that have many close relatives. This could be explained either by climate‐driven diffuse cospeciation between plants and insects, or by elevated speciation and reduced extinction in herbivore lineages associated with expanding host taxa (resources). Progress in paleovegetation reconstructions in combination with the rapidly increasing availability of fossil‐calibrated phylogenies provide means to discern between these alternative hypotheses. In particular, the ‘Diffuse cospeciation’ scenario predicts closely matching main diversification periods in plants and in the insects that feed upon them, while the ‘Resource abundance‐dependent diversification’ hypothesis predicts that both positive and negative responses of insect diversity are lagged in relation to host‐plant availability. The dramatic Cenozoic changes in global climate provide multiple possibilities for studying the mechanisms by which climatic shifts may drive diversity dynamics in plants and insect herbivores.
Seasonality and monthly dynamics of marine myovirus communities
Authors: Chow Cheryl‐Emiliane T. , Fuhrman Jed A.
Published: April 2012

Marine myoviruses (i.e. bacteriophages with a contractile tail sheath) are numerically abundant and genetically diverse. We developed a terminal restriction fragment length polymorphism assay (TRFLP) for g23, the conserved gene encoding the major capsid protein, to investigate T4‐like myovirus communities at USC's Microbial Observatory at the San Pedro Ocean Time‐series (SPOT), where we previously reported bacterial seasonality. Between 71 and 154 operational taxonomic units (OTUs) were observed monthly over 3 years. Roughly 25% of OTUs were detected in 31 or more months. T4‐like myoviral community structure varied seasonally with some OTUs peaking repeatedly in spring–summer and others in fall–winter, while moderately abundant OTUs persisted year‐round. Recurring community structure was demonstrated using discriminant function analysis (DFA, selecting taxa that best predict months) and average Bray–Curtis similarity. DFA showed communities from adjacent months or 12 months apart were positively auto‐correlated, while communities 3–7 months apart were negatively auto‐correlated. Bray–Curtis similarity was highest between adjacent months – with a local maximum at 12‐month and local minima at 6‐ and 18‐ to 20‐month lags. The T4‐like virus community at SPOT exhibited seasonality, yet the somewhat unexpected persistence of moderately abundant OTUs and predictability of the community add new twists to existing conceptual models of marine viruses.
Plasticity of symbiont acquisition throughout the life cycle of the shallow‐water tropical lucinid Codakia orbiculata (Mollusca: Bivalvia)
Authors: Gros Olivier , Elisabeth Nathalie H. , Gustave Sylvie D. D. , Caro Audrey , Dubilier Nicole
Published: April 2012

In marine invertebrates that acquire their symbionts from the environment, these are generally only taken up during early developmental stages. In the symbiosis between lucinid clams and their intracellular sulfur‐oxidizing bacteria, it has been shown that the juveniles acquire their symbionts from an environmental stock of free‐living symbiont forms, but it is not known if adult clams are still competent to take up symbiotic bacteria from the environment. In this study, we investigated symbiont acquisition in adult specimens of the lucinid clam Codakia orbiculata, using transmission electron microscopy, fluorescence in situ hybridization, immunohistochemistry and PCR. We show here that adults that had no detectable symbionts after starvation in aquaria for 6 months, rapidly reacquired symbionts within days after being returned to their natural environments in the field. Control specimens that were starved and then exposed to seawater aquaria with sulfide did not reacquire symbionts. This indicates that the reacquisition of symbionts in the starved clams returned to the field was not caused by high division rates of a small pool of remaining symbionts that we were not able to detect with the methods used here. Immunohistochemistry with an antibody against actin, a protein involved in the phagocytosis of intracellular bacteria, showed that actin was expressed at the apical ends of the gill cells that took up symbionts, providing further evidence that the symbionts were acquired from the environment. Interestingly, actin expression was also observed in symbiont‐containing cells of untreated lucinids freshly collected from the environment, indicating that symbiont acquisition from the environment occurs continuously in these clams throughout their lifetime.
Sunitinib causes dose‐dependent negative functional effects on myocardium and cardiomyocytes
Authors: Rainer Peter P. , Doleschal Bernhard , Kirk Jonathan A. , Sivakumaran Vidhya , Saad Zora , Groschner Klaus , Maechler Heinrich , Hoefler Gerald , Bauernhofer Thomas , Samonigg Hellmut , Hutterer Georg , Kass David A. , Pieske Burkert , von Lewinski Dirk , Pichler Martin
Published: April 2012

Study Type – Aetiology (case control)

Level of Evidence 2b

What's known on the subject? and What does the study add?

The multikinase inhibitor sunitinib causes cardiotoxic side effects in a substantial number of treated patients. Previously, data from clinical studies suggested that these side effects are more frequently found in patients with a lower body mass index, but the reasons for this toxic effect remain elusive.

In this study we determined, in a human multicellular model, that sunitinib causes an impairment of the contractile function of cardiomyocytes in a dose‐dependent manner. Furthermore, we found that sunitinib induces alterations in calcium homeostasis in cardiomyocytes. In addition, an increased production of reactive oxygen species after exposure of cardiomyocytes to this drug was detected. These findings suggest that measurement of plasma concentration might help to control cardiotoxic side effects and optimize a more personalized application of this drug.

OBJECTIVES

To examine the acute effects of sunitinib on inotropic function, intracellular Ca2+ transients, myofilament Ca2+ sensitivity and generation of reactive oxygen species (ROS) in human multicellular myocardium and isolated mouse cardiomyocytes.

To search for microRNAs as suitable biomarkers for indicating toxic cardiac effects.

PATIENTS AND METHODS

After exposure to sunitinib (0.1–10 µg/mL) developed force, diastolic tension and kinetic variables were assessed in isolated human myocardium.

Changes in myocyte sarcomere length, whole‐cell calcium transients, myofilament force‐Ca2+ relationship, and ROS generation were examined in isolated ventricular mouse cardiomyocytes.

Microarray and realtime‐PCR were used to screen for differentially expressed microRNAs in cultured cardiomyocytes that were exposed for 24 h to sunitinib.

RESULTS

We found that higher concentrations of sunitinib (1 and 10 µg/mL) decreased developed force at 30 minutes 76.9 + 2.8 and 54.5 + 6.3%, compared to 96.1 + 2.6% in controls (P < 0.01).

Sunitinib exposure significantly decreased sarcomere shortening and Ca2+ transients.

Myofilament Ca2+ sensitivity was not altered, while ROS levels were significantly increased after exposure to the drug.

MicroRNA expression patterns were not altered by sunitinib.

CONCLUSIONS

Sunitinib elicits a dose‐dependent negative inotropic effect in myocardium, accompanied by a decline in intracellular Ca2+ and increased ROS generation.

In clinical practice, these cardiotoxic effects should be considered in cases where cardiac concentrations of sunitinib could be increased.
Statins and glycaemic control—a cause for concern?
Authors: Hitman G. A.
Published: April 2012

Diabet. Med. 29, 557 (2012)
Hyperglycaemia monitoring and management in stroke care: policy vs. practice
Authors: Mitchell E. A. , Coates V. E. , Ryan A. A. , McCarron M. O. , Lyttle D. , McCrum‐Gardner E.
Published: April 2012

Diabet. Med. 29, 1108–1114 (2012)

Aim  To evaluate the extent to which hyperglycaemia was monitored and managed among patients admitted to hospital with acute stroke and transient ischaemic attack.

Methods  We conducted a retrospective cohort study involving a review of the records of 112 patients consecutively admitted with acute stroke or transient ischaemic attack to all three district general hospitals in one Health and Social Care Trust in Northern Ireland from 1 January to 15 April 2008. Glucose results for each of the first 5 days of hospital admission were ascertained. We compared interventions, clinical outcome and discharge planning between patients who experienced glucose ≥ 7.8 mmol/l in the first 5 days, and patients with lower glucose results.

Results  The daily prevalence rate of hyperglycaemia > 7.8 mmol/l across the first 5 days ranged from 24 to 34%. A total of 41 (37%) patients experienced hyperglycaemia on at least one occasion during the first 5 days. A history of diabetes mellitus prompted near patient glucose testing, but, among patients without diagnosed diabetes, glycaemia was under‐monitored. Hyperglycaemia was a persisting trend, was under‐treated and under‐reported to general practitioners. Elevated glucose results failed to influence higher rates of fasting plasma glucose tests and BMI assessment.

Conclusions  There is a need for greater vigilance in the detection of hyperglycaemia and undiagnosed diabetes mellitus among patients admitted to hospital with stroke or transient ischaemic attack.
The influence of neighbourhood disadvantage on smoking cessation and its contribution to inequalities in smoking status
Authors: TURRELL GAVIN , HEWITT BELINDA A. , MILLER SOPHIE A.
Published: April 2012

Introduction and Aims. Individual smokers from disadvantaged backgrounds are less likely to quit, which contributes to widening inequalities in smoking. Residents of disadvantaged neighbourhoods are more likely to smoke, and neighbourhood inequalities in smoking may also be widening because of neighbourhood differences in rates of cessation. This study examined the association between neighbourhood disadvantage and smoking cessation and its relationship with neighbourhood inequalities in smoking.

Design and Methods. A multilevel longitudinal study of mid‐aged (40–67 years) residents (n = 6915) of Brisbane, Australia, who lived in the same neighbourhoods (n = 200) in 2007 and 2009. Neighbourhood inequalities in cessation and smoking were analysed using multilevel logistic regression and Markov chain Monte Carlo simulation.

Results. After adjustment for individual‐level socioeconomic factors, the probability of quitting smoking between 2007 and 2009 was lower for residents of disadvantaged neighbourhoods (9.0–12.8%) than their counterparts in more advantaged neighbourhoods (20.7–22.5%). These inequalities in cessation manifested in widening inequalities in smoking: in 2007 the between‐neighbourhood variance in rates of smoking was 0.242 (P ≤ 0.001) and in 2009 it was 0.260 (P ≤ 0.001). In 2007, residents of the most disadvantaged neighbourhoods were 88% (OR 1.88, 95% credible intervals (CrI) 1.41–2.49) more likely to smoke than residents in the least disadvantaged neighbourhoods: the corresponding difference in 2009 was 98% (OR 1.98, 95% CrI 1.48–2.66).

Conclusion. Fundamentally, social and economic inequalities at the neighbourhood and individual levels cause smoking and cessation inequalities. Reducing these inequalities will require comprehensive, well‐funded and targeted tobacco control efforts and equity‐based policies that address the social and economic determinants of smoking. [Turrell G, Hewitt BA, Miller SA. The influence of neighbourhood disadvantage on smoking cessation and its contribution to inequalities in smoking status. Drug Alcohol Rev 2012;31:645–652]
Towards a relational framework for pathological gambling (Part II): Congruence
Authors: Lee Bonnie K.
Published: April 2012

In an illustrative clinical case study, congruence is depicted as the fifth circuit in a relational framework to extricate gambler and spouse from pathological gambling and its after‐effects. Congruence couple therapy poses interventions in four dimensions of the couple experience: (i) intra‐psychic; (ii) interpersonal; (iii) intergenerational and (iv) universal‐spiritual. Congruence is operationalized as awareness, attention, acknowledgment and the alignment of the four dimensions. The philosophical underpinnings of this concept‐based model are laid out with clinical vignettes. The couple reported improved relationship quality with a reduction of gambling urges and maintained abstinence. The couple relationship serves as leverage for both gambler and spouse to reconnect with themselves, with each other, with their intrinsic worth and dignity and with their family of origin experiences. As such, congruence couple therapy goes beyond the level of the individual and intra‐psychic to reconstruct key family relationships in both past and present, and to rebuild spiritual resources to fortify the couple's capital for sustained recovery.
ON THE PLAUSIBILITY OF HOMEOPATHIC ‘SIMILITUDE’
Authors: BELLAVITE PAOLO
Published: April 2012

The homeopathic principle of similitude is not based on the principle of vaccination but on the more general principle of inversion of effects, a widespread medical phenomenon. Based on the systemic networks which play an important role in response to stress, this principle concerns the reorganization of regulation systems, through a coherent response to the medicine. This model is backed by a large number of published studies from our laboratory and others, by toxicological evidence such as the emerging fields of ‘hormesis’, of neuropharmacology, and of systems biology. The immune system is just one example of the possible application of this law of similitude, which constitutes the true ‘heart’ of the homeopathic idea, and again ethically justifies the attempt to apply it to experimental pharmacology.
IS HOMEOPATHY REALLY ‘MORALLY AND ETHICALLY UNACCEPTABLE’? A CRITIQUE OF PURE SCIENTISM
Authors: MILGROM LIONEL , CHATFIELD KATE
Published: April 2012

In this short response we show that Kevin Smith's moral and ethical rejections of homeopathy1 are fallacious and rest on questionable epistemology. Further, we suggest Smith's presumption of a utilitarian stance is an example of scientism encroaching into medicine.
HOMEOPATHY AND EXTRAORDINARY CLAIMS – A RESPONSE TO SMITH'S UTILITARIAN ARGUMENT
Authors: SEBASTIAN IRENE
Published: April 2012

Kevin Smith's utilitarian argument against homeopathy1 is flawed because he did not review and refute the relevant basic science literature on ultra‐high dilutions. He also failed to appreciate that allopathic medicine is based on a deductive‐nomothetic method and that homeopathic medicine is based on an inductive‐idiographic method, and thus that the implications for clinical research are very different. His misunderstanding of provings and of the holism of homeopathic medicine also demonstrated his failure to understand the history, philosophy and method of homeopathy. Finally, I questioned the value of introducing ethical judgment into an ongoing scientific debate.
Is Something Better Than Nothing? An Evaluation of Early Childhood Programs in Cambodia
Authors: Rao Nirmala , Sun Jin , Pearson Veronica , Pearson Emma , Liu Hongyun , Constas Mark A. , Engle Patrice L.
Published: April 2012

This study evaluated the relative effectiveness of home‐based, community‐based, and state‐run early childhood programs across Cambodia. A total of 880 five‐year‐olds (55% girls) from 6 rural provinces in Cambodia attending State Preschools, Community Preschools, Home‐Based Programs, or no programs were assessed twice using the Cambodian Developmental Assessment Test. Controlling for baseline differences, children who participated in any early childhood programs performed significantly better in posttest than those of children who did not participate in any programs. Children in State Preschools scored significantly higher than those in either Community Preschools or Home‐Based Programs; scores did not differ as a function of attending Community Preschools or Home‐Based Programs. The results indicate that some preschool experience is better than none at all.
Maternal Depressive Symptoms, Dysfunctional Cognitions, and Infant Night Waking: The Role of Maternal Nighttime Behavior
Authors: Teti Douglas M. , Crosby Brian
Published: April 2012

Mechanisms were examined to clarify relations between maternal depressive symptoms, dysfunctional cognitions, and infant night waking among 45 infants (1–24 months) and their mothers. A mother‐driven mediational model was tested in which maternal depressive symptoms and dysfunctional cognitions about infant sleep predicted infant night waking via their impact on mothers’ bedtime and nighttime behavior with infants (from video). Two infant‐driven mediational models were also examined, in which infant night waking predicted maternal depressive symptoms, or dysfunctional cognitions, via their impact on nighttime maternal behavior. Stronger support for the mother‐driven model was obtained, which was further supported by qualitative observations from video‐recordings. This study provides important insights about maternal depression’s effects on nighttime parenting, and how such parenting affects infant sleep.
Development Aid to Agriculture and Economic Growth
Authors: Kaya Ozgur , Kaya Ilker , Gunter Lewell
Published: April 2012

The link between foreign aid and economic growth has been a controversial issue with no strong consensus so far. This paper argues that a possible reason why some studies may conclude that aid is ineffective in promoting economic growth might be that not all aid is given for development purposes (i.e. aid given for strategic considerations, humanitarian reasons or emergency relief). This study classifies foreign aid into four subcategories: agricultural aid, social infrastructure aid, investment aid, and non‐investment aid. Using the generalized method of moments (GMM) estimation technique on a Barro type growth regression with panel data from the aid recipient economies, this paper finds that when aid is directed to the agricultural sector of the developing countries, it is positively and significantly related to growth and can affect economic growth in the short run.