bluuebunny/crossref_metadata_2025 huggingface dataset:
Activation of RANKL‐induced osteoclasts and memory T lymphocytes by Porphyromonas gingivalis is serotype dependant
Authors: Vernal Rolando , Díaz‐Zúñiga Jaime , Melgar‐Rodríguez Samanta , Pujol Myriam , Diaz‐Guerra Eva , Silva Augusto , Sanz Mariano , Garcia‐Sanz Jose A.
Published: January 2014

Aim

Destructive periodontitis is associated with a Th1–Th17 immune response and activation of RANKL‐induced osteoclasts. In addition, Porphyromonas gingivalis K1 and K2 serotypes induce a strong Th1–Th17 response. This study aimed to investigate whether these P. gingivalis serotypes induce higher osteoclasts activation, by increased Th17‐associated RANKL production, and an antigen‐specific memory T‐lymphocyte response.

Material and Methods

The RANKL production and TRAP+ osteoclast induction were quantified on naïve T lymphocytes stimulated with dendritic cells primed with the P. gingivalis serotypes. The T‐bet, GATA‐3, RORC2 and Foxp3 expression was correlated with RANKL production. The frequency of proliferating memory T lymphocytes in response to P. gingivalis serotypes was determined in both periodontitis and healthy subjects.

Results

T lymphocytes stimulated by K1 or K2‐primed dendritic cells elicited higher levels of RANKL and TRAP+ osteoclasts than cells stimulated with the other serotypes. RANKL positively correlated with RORC2. Whereas periodontitis patients had a higher frequency of memory T lymphocytes responding to K1 or K2, healthy subjects had a higher frequency of memory T lymphocytes responding to K4 or K−.

Conclusions

P. gingivalis serotypes K1 and K2, but not others, are associated with an increased production of the osteoclastogenesis‐related factor RANKL. This important information suggests that these serotypes could elicit a greater bone resorption in vivo and have a role in the periodontitis pathogenesis.
How the length of genital parts affects copulation performance in a carabid beetle: implications for correlated genital evolution between the sexes
Authors: Okuzaki Y. , Sota T.
Published: January 2014

To identify factors leading to the correlated evolution of exaggerated male and female genitalia, we studied the effects of the variable dimensions of corresponding functional genital parts (male copulatory piece and female vaginal appendix) on copulatory performance in the polygamous carabid beetle Carabus (Ohomopterus) maiyasanus. We used mating pairs of individuals from two populations to increase the variances in genital dimensions and determined the copulation performance (insemination and spermatophore replacement, and copulation time) in single‐ and double‐mating situations. In single mating, insemination success was not affected by genital dimensions, although the copulation time was significantly shorter when the male aedeagus was longer. In the double‐mating experiment, insemination and replacement of spermatophores by the second male succeeded more frequently when the copulatory piece was shorter and the vaginal appendix was longer, and when the difference between the length of the copulatory piece and the vaginal appendix was smaller. Thus, a matching of the corresponding genital parts between the sexes increases the male's reproductive success in sperm competition, but elongation of the copulatory piece cannot be explained simply by the improvement in male reproductive success. We discuss possible factors for the elongation of genital parts in terms of sexual conflict and reproductive interference through interspecific copulation.
Compatibility between Forficula auricularia and entomopathogenic nematodes to be used in pome fruit pest management
Authors: Lordan J. , Alegre S. , Alins G. , Sarasúa M. J. , Morton A. , García del Pino F.
Published: January 2014

Use of predators, parasitoids and entomopathogens as biocontrol agents in pome fruit production can lead to more efficient and sustainable pest management programmes. The European earwig (Forficula auricularia Linnaeus [Dermaptera: Forficulidae]) is a major predator of key pests in pome fruit orchards, and entomopathogenic nematodes (EPNs) of the families Steinernematidae and Heterorhabditidae are obligate parasites of a large number of insect species. Therefore, the interaction between earwigs and EPNs can play an important role in pest management programmes. Susceptibility of the European earwig to Steinernema carpocapsae, Steinernema feltiae (Steinernematidae) and Heterorhabditis bacteriophora (Heterorhabditidae) was evaluated. S. carpocapsae was the only tested EPN capable of killing the European earwig. However, the European earwig can detect the presence of S. carpocapsae and therefore avoid nematode‐treated shelters. An earwig deterrent activity in EPN‐killed codling moth larvae that reduces the foraging of European earwig on insect cadavers containing nematodes and allows nematodes to complete their life cycle was also assessed with the three species of nematodes. These findings suggest a positive compatibility between the European earwig and EPNs.
Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: A meta‐analysis of diagnostic accuracy
Authors: Shi Ke‐Qing , Tang Jun‐Zhou , Zhu Xue‐Lian , Ying Li , Li De‐Wei , Gao Jian , Fang Yu‐Xiao , Li Gui‐Ling , Song Yi‐Jiang , Deng Zhu‐Jun , Wu Jian‐Min , Tang Kai‐Fu
Published: January 2014

Background and Aim

Controlled attenuation parameter (CAP) is a novel ultrasound‐based elastography method for detection of steatosis severity. This meta‐analysis aimed to assess the performance of CAP.

Methods

PubMed, the Cochrane Library, and the Web of Knowledge were searched to find studies, published in English, relating to accuracy evaluations of CAP for detecting stage 1 (S1), stage 2 (S2), or stage 3 (S3) hepatic steatosis which was diagnosed by liver biopsy. Sensitivities, specificities, and hierarchical summary receiver operating characteristic (HSROC) curves were used to examine CAP performance. The clinical utility of CAP was also evaluated.

Results

Nine studies, with 11 cohorts were analyzed. The summary sensitivities and specificities values were 0.78 (95% confidence interval [CI], 0.69–0.84) and 0.79 (95% CI, 0.68–0.86) for ≥ S1, 0.85 (95% CI, 0.74–0.92) and 0.79 (95% CI, 0.71–0.85) for ≥ S2, and 0.83 (95% CI, 0.76–0.89) and 0.79 (95% CI, 0.68–0.87) for ≥ S3. The HSROCs were 0.85 (95% CI, 0.81–88) for ≥ S1, 0.88 (95% CI, 0.85–0.91) for ≥ S2, and 0.87 (95% CI, 0.84–0.90) for ≥ S3. Following a “positive” measurement (over the threshold value) for ≥ S1, ≥ S2, and ≥ S3, the corresponding post‐test probabilities for the presence of steatosis (pretest probability was 50%) were 78%, 80% and 80%, respectively; if the values were below these thresholds (“negative” results), the post‐test probabilities were 22%, 16%, and 17%, respectively.

Conclusions

CAP has good sensitivity and specificity for detecting hepatic steatosis; however, based on a meta‐analysis, CAP was limited in their accuracy of steatosis, which precluded widespread use in clinical practice.
GluN2D‐containing NMDA receptors inhibit neurotransmission in the mouse striatum through a cholinergic mechanism: implication for Parkinson's disease
Authors: Zhang Xiaoqun , Feng Ze‐Jun , Chergui Karima
Published: January 2014

The GluN2 subunits that compose NMDA receptors (NMDARs) determine functional and pharmacological properties of the receptor. In the striatum, functions and potential dysfunctions of NMDARs attributed to specific GluN2 subunits have not been clearly elucidated, although NMDARs play critical roles in the interactions between glutamate and dopamine. Through the use of amperometry and field potential recordings in mouse brain slices, we found that NMDARs that contain the GluN2D subunit contribute to NMDA‐induced inhibition of evoked dopamine release and of glutamatergic neurotransmission in the striatum of control mice. Inhibition is likely mediated through increased firing in cholinergic interneurons, which were shown to express GluN2D. Indeed, NMDA‐induced inhibition of both dopamine release and glutamatergic neurotransmission is reduced in the presence of muscarinic receptor antagonists and is mimicked by a muscarinic receptor agonist. We have also examined whether this function of GluN2D‐containing NMDARs is altered in a mouse model of Parkinson's disease. We found that the inhibitory role of GluN2D‐containing NMDARs on glutamatergic neurotransmission is impaired in the 6‐hydroxydopamine lesioned striatum. These results identify a role for GluN2D‐containing NMDARs and adaptive changes in experimental Parkinsonism. GluN2D might constitute an attractive target for the development of novel pharmacological tools for therapeutic intervention in Parkinson's disease.

image

We have examined the role of NMDA receptors composed of the GluN2D subunit in the mouse striatum. These receptors inhibit the release of dopamine and of glutamate through a mechanism that involves activation of cholinergic interneurons. This inhibitory role is impaired in the dopamine‐depleted striatum. This study identifies GluN2D as a potential target for therapeutic intervention in Parkinson's disease.
Alanine‐(87)‐threonine polymorphism impairs signaling and internalization of the human P2Y11 receptor, when co‐expressed with the P2Y1 receptor
Authors: Haas Michael , Shaaban Ahmed , Reiser Georg
Published: January 2014

The P2Y11 nucleotide receptor detects high extracellular ATP concentrations. Mutations of the human P2RY11 gene can play a role in brain autoimmune responses, and the P2Y11 receptor alanine‐87‐threonine (A87T) polymorphism has been suggested to affect immune‐system functions. We investigated receptor functionality of the P2Y11A87T mutant using HEK293 and 1321N1 astrocytoma cells. In HEK293 cells, the P2Y11 receptor agonist 3′‐O‐(4‐benzoylbenzoyl)adenosine 5′‐triphosphate (BzATP) was completely inactive in evoking intracellular calcium release while the potency of ATP was reduced. ATP was also less potent in triggering cAMP generation. However, 1321N1 astrocytoma cells, which lack any endogenous P2Y1 receptors, did not display a reduction. Only when 1321N1 cells were co‐transfected with P2Y11A87T and P2Y1 receptors, the calcium responses to the P2Y11 receptor‐specific agonist BzATP were reduced. It is already known that P2Y1 and P2Y11 receptors interact. We thus conclude that the physiological impact of A87T mutation of the P2Y11 receptor derives from detrimental effects on P2Y1–P2Y11 receptor interaction. We additionally investigated alanine‐87‐serine and alanine‐87‐tyrosine P2Y11 receptor mutants. Both mutations rescue the response to BzATP in HEK293 cells, thus ruling out polarity of amino acid‐87 to be the molecular basis for altered receptor characteristics. We further found that the P2Y11A87T receptor shows complete loss of nucleotide‐induced internalization in HEK293 cells. Thus, we demonstrate impaired signaling of the P2Y11 A87T‐mutated receptors when co‐operating with P2Y1 receptors.

image

The human P2Y11 nucleotide receptor plays key role in immune‐responses in brain and other tissues. We provide evidence for significant functional disturbance of the P2Y11 receptor carrying the Alanine‐87‐Threonine mutation caused by natural polymorphism. This receptor defect is apparent only when co‐expressed with P2Y1 receptors. We found reductions in ligand‐induced calcium and cAMP responses and in nucleotide‐induced receptor internalization / resensitization. Thus, prolonged nucleotide treatments are the basis for the molecular defects of the mutant receptor in diseases.
MRS glucose mapping and PET joining forces: re‐evaluation of the lumped constant in the rat brain under isoflurane anaesthesia
Authors: Alf Malte F. , Duarte João M. N. , Lei Hongxia , Krämer Stefanie D. , Mlynarik Vladimir , Schibli Roger , Gruetter Rolf
Published: January 2014

Although numerous positron emission tomography (PET) studies with 18F‐fluoro‐deoxyglucose (FDG) have reported quantitative results on cerebral glucose kinetics and consumption, there is a large variation between the absolute values found in the literature. One of the underlying causes is the inconsistent use of the lumped constants (LCs), the derivation of which is often based on multiple assumptions that render absolute numbers imprecise and errors hard to quantify. We combined a kinetic FDG‐PET study with magnetic resonance spectroscopic imaging (MRSI) of glucose dynamics in Sprague–Dawley rats to obtain a more comprehensive view of brain glucose kinetics and determine a reliable value for the LC under isoflurane anaesthesia. Maps of Tmax/CMRglc derived from MRSI data and Tmax determined from PET kinetic modelling allowed to obtain an LC‐independent CMRglc. The LC was estimated to range from 0.33 ± 0.07 in retrosplenial cortex to 0.44 ± 0.05 in hippocampus, yielding CMRglc between 62 ± 14 and 54 ± 11 μmol/min/100 g, respectively. These newly determined LCs for four distinct areas in the rat brain under isoflurane anaesthesia provide means of comparing the growing amount of FDG‐PET data available from translational studies.

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The lumped constant (LC) is a correction factor employed to estimate the glucose metabolic rate (CMRglc) from the metabolic rate of a radioactive glucose analog such as 18F‐fluorodeoxyglucose (FDG). By combining FDG positron emission tomography (PET) with magnetic resonance spectroscopic imaging (MRSI) of glucose dynamics, we determined the FDG LC in the rat brain under isoflurane anaesthesia.
Chronic inflammatory demyelinating polyradiculoneuropathy and variants: where we are and where we should go
Authors: Nobile‐Orazio Eduardo
Published: January 2014

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a chronic and often disabling sensory motor neuropathy postulated as caused by an immune attack against peripheral nerve myelin. In addition to a classic sensory–motor polyneuropathy, other phenotypes of CIDP have been described including the Lewis‐Sumner syndrome, distal acquired demyelinating symmetric (DADS) neuropathy, pure motor CIDP, pure sensory CIDP including chronic immune sensory polyradiculopathy (CISP), and focal CIDP. These phenotypes are currently considered to be variants of CIDP, even if the possibility that they represent different demyelinating neuropathies cannot be fully excluded considering differences in their response to therapy. Several data support the role of the immune system in the pathogenesis of CIDP even if the precise targets and actors (antibodies and lymphocytes) of this immune response remain uncertain. Recent studies have shown that the therapeutic response may differ in patients with peculiar clinical presentations supporting the hypothesis that different pathogenetic mechanisms may underlie the heterogeneity of CIDP. The majority of patients with CIDP show improvement after immune therapies including corticosteroids, plasma exchange, and high‐dose intravenous immunoglobulin (IVIg). It remains unclear why none of the other immune therapies that were reported to be variably effective in other immune disorders proved to be effective also in CIDP.
Distribution of sensory nerve endings around the human sinus tarsi: a cadaver study
Authors: Rein Susanne , Manthey Suzanne , Zwipp Hans , Witt Andreas
Published: January 2014

The aim of this study was to analyse the pattern of sensory nerve endings and blood vessels around the sinus tarsi. The superficial and deep parts of the fat pads at the inferior extensor retinaculum (IER) as well as the subtalar joint capsule inside the sinus tarsi from 13 cadaver feet were dissected. The distribution of the sensory nerve endings and blood vessels were analysed in the resected specimens as the number per cm2 after staining with haematoxylin‐eosin, S100 protein, low‐affinity neurotrophin receptor p75, and protein gene product 9.5 using the classification of Freeman and Wyke. Free nerve endings were the predominant sensory ending (P < 0.001). Ruffini and Golgi‐like endings were rarely found and no Pacini corpuscles were seen. Significantly more free nerve endings (P < 0.001) and blood vessels (P = 0.01) were observed in the subtalar joint capsule than in the superficial part of the fat pad at the IER. The deep part of the fat pad at the IER had significantly more blood vessels than the superficial part of the fat pad at the IER (P = 0.012). Significantly more blood vessels than free nerve endings were seen in all three groups (P < 0.001). No significant differences in distribution were seen in terms of right or left side, except for free nerve endings in the superficial part of the fat pad at the IER (P = 0.003). A greater number of free nerve endings correlated with a greater number of blood vessels. The presence of sensory nerve endings between individual fat cells supports the hypothesis that the fat pad has a proprioceptive role monitoring changes and that it is a source of pain in sinus tarsi syndrome due to the abundance of free nerve endings.
Consumers' Optimism Bias and Responses to Risk Disclosures in Direct‐to‐Consumer (DTC) Prescription Drug Advertising: The Moderating Role of Subjective Health Literacy
Authors: AHN HO‐YOUNG (ANTHONY) , PARK JIN SEONG , HALEY ERIC
Published: January 2014

Despite a substantial body of research in direct‐to‐consumer advertising (DTCA) for prescription drugs, what is missing from the existing discussion on the risk disclosure in DTCA is a focus on the roles of individual motivation and ability to process risk information. Guided by the Elaboration Likelihood Model (ELM) and the Motivation‐Ability‐Opportunity framework, the current study examines the roles of the consumer's optimism bias and subjective health literacy in responding to the risk disclosure in DTCA. By analyzing survey data (N = 404), the study reveals that: (1) consumers who show a tendency to believe that they are at less risk of experiencing adverse reactions to prescription drugs than their peers are less likely to pay attention to the risk disclosure or intend to seek further information about the health risks of drugs, (2) the relationship between optimism bias and information‐seeking intentions is stronger for consumers with high subjective health literacy than for those with low health literacy. Implications and recommendations are provided.
Proposal of a concept and design of a randomized phase III trial investigating the survival effect of para‐aortic lymphadenectomy in endometrial cancer
Authors: Watari Hidemichi , Todo Yukiharu , Kang Sokbom , Odagiri Tetsuji , Sakuragi Noriaki
Published: January 2014

Although prospective studies have failed to show the therapeutic effect of lymphadenectomy in the surgical treatment of endometrial cancer, several retrospective studies including the SEPAL study revealed the survival effect of lymphadenectomy. To prospectively investigate the survival benefit of para‐aortic lymphadenectomy shown in the SEPAL study, we are proposing a new concept of a randomized phase III trial. An appropriate study population will be selected according to the preoperative assessments (evaluation of myometrial invasion and cervical invasion with magnetic resonance imaging, extrauterine spread with computed tomography, and histological type and grade by pathological evaluation) to estimate the risk of lymph node metastasis. Patients relevant to potential International Federation of Gynecology and Obstetrics (2008) stage IB, II and III diseases will be eligible, and randomly assigned to two arms: pelvic lymphadenectomy alone (control), or pelvic and para‐aortic lymphadenectomy (experimental). After initial surgery, patients with postoperative pathological risk factors for recurrence will receive adjuvant chemotherapy. Because we aim to investigate the therapeutic significance of primary treatments, including surgery and adjuvant chemotherapy, the primary end‐point could be recurrence‐free survival. One of the most important issues to successfully perform this prospective study is to assure the quality of lymphadenectomy (extent and area), which could be evaluated based on the number of harvested nodes and objective evaluation of dissected area by videos and/or photos.
Tailoring lymphadenectomy according to the risk of lymph node metastasis in endometrial cancer
Authors: Todo Yukiharu , Watari Hidemichi , Kang Sokbom , Sakuragi Noriaki
Published: January 2014

It has been strongly suggested that patients with endometrial cancer with low risk of lymph node metastasis do not benefit from lymphadenectomy and that intermediate‐risk/high‐risk endometrial cancer patients benefit from complete pelvic and para‐aortic lymphadenectomy. This hypothesis needs to be validated by prospective studies. For randomized controlled trials (RCT), heterogeneity of intervention compromises internal validity and non‐participation of experienced doctors compromises external validity. As these situations easily occur in randomized surgical trials (RST) intended for high‐risk patients, the effects of complicated surgery, such as full lymphadenectomy, might be underestimated in RST. In a famous RST, data for all eligible patients implied that survival outcome for the non‐randomized group was significantly better than that for the randomized group. One plausible explanation is that physicians' judgment and experience produce better treatment decisions than do random choices. Although two RCT from European countries showed negative results of lymphadenectomy on prognosis, valuing the care of individual patients may be more important than uncritically adopting the results of RCT. In endometrial cancer, lymphadenectomy must be tailored to maximize the therapeutic effect of surgery and minimize its invasiveness and adverse effects. Two strategies are: (i) to remove lymph nodes most likely to harbor disease while sparing lymph nodes that are unlikely to be affected; and (ii) to perform full lymphadenectomies only on patients who can potentially benefit from them. Here, we focus on the second strategy. Preoperative risk assessments used in Japan and Korea to select low‐risk patients who would not benefit from lymphadenectomy are discussed.
Annual report of Gynecologic Oncology Committee, Japan Society of Obstetrics and Gynecology, 2013
Authors: Aoki Daisuke
Published: January 2014

We present the Patient Annual Report in 2011 and the Treatment Annual Report in 2005 that were collected and analyzed by the Japan Society of Obstetrics and Gynecology. Data on 15 698 patients with cervical cancer, 7713 with endometrial cancer and 4672 with ovarian cancer in whom treatment was started in 2011 and data on the prognosis of 2985 patients with cervical cancer, 2812 with endometrial cancer, and 1839 with ovarian cancer who were started on treatment in 2005 were analyzed and summarized. Patient Annual Report in 2011: Stage 0 accounted for 58%, stage I for 24%, stage II for 9%, stage III for 5%, and stage IV for 4% of all the patients with cervical cancer. Stage 0 accounted for 6%, stage I for 61%, stage II for 8%, stage III for 18%, and stage IV for 7% of patients with endometrial cancer. Stage I accounted for 43%, stage II for 9%, stage III for 29%, and stage IV for 8% of patients with ovarian cancer. Treatment Annual Report in 2005: The 5‐year overall survival rates of patients with cervical cancer were 91% in stage I, 78% in stage II, 57% in stage III, and 30% in stage IV. The 5‐year overall survival rates of patients with endometrial cancer were 95% in stage I, 89% in stage II, 77% in stage III, and 23% in stage IV. The 5‐year overall survival rates of patients with ovarian surface epithelial‐stromal tumors were 92% in stage I, 75% in stage II, 50% in stage III and 39% in stage IV.
The wisdom of letting go and performance: The moderating role of emotional intelligence and discrete emotions
Authors: Gooty Janaki , Gavin Mark B. , Ashkanasy Neal M. , Thomas Jane S.
Published: January 2014

Drawing upon cognitive appraisal theory and affective events theory, we develop and test a model of discrete emotions, coping, and performance that contains both within‐ and between‐person components. We argue that when employees feel angry, guilty, joyous, or proud at work, those with higher levels of ability‐based emotional intelligence will turn to emotion‐focused coping as a means to deal with the immediate aftermath of the emotion. This form of coping requires the least amount of cognitive resources and facilitates performance by helping individuals to meet their task demands. Random coefficient modelling findings from daily diary data collected in a law enforcement setting support our proposed ideas concerning the interactive effects of emotions and emotional intelligence on coping, as well as the effects of coping on task performance.

Practitioner points

The findings from this study conducted in a law enforcement setting suggest that coping strategies such as venting, denial, and disengagement might be adaptive for short‐term performance.

Organizations could manage employee emotions via awareness of appropriate coping responses and selecting higherABEIindividuals for jobs that involve emotions on a routine basis.
Neurobiological Processes of Risk and Resilience in Adolescence: Implications for Policy and Prevention Science
Authors: Busso Daniel S.
Published: January 2014

This article focuses on the concepts of risk and resilience and their potential to inform clinical interventions, school‐based prevention programs, and social policies. Research suggests that childhood adversity can trigger a cascade of psychological and neurobiological events that can lead to mental disorders in later life. Yet little is known about how these processes manifest in adolescence, a developmental window that is typically associated with an elevated risk for psychopathology and represents a period of neurological growth and reorganization that is second only to early childhood. A better understanding of adolescent brain development may provide an empirical grounding to improve the focus and timing of interventions, particularly those that target self‐regulation, meta‐cognition, and social supports. Finally, opportunities and challenges that emerge when bridging neuroscience and prevention science are discussed.
Food Choice Is Multifaceted, Contextual, Dynamic, Multilevel, Integrated, and Diverse
Authors: Sobal Jeffery , Bisogni Carole A. , Jastran Margaret
Published: January 2014

Eating is broadly conceptualized as food choice. Food choice is a complex activity with many dimensions. Food choice is multifaceted as it involves whether, where, when, how long, how, why, with whom, for whom, and under what conditions eating occurs. Food choice is contextual as it is situated within specific conditions and settings involving both individuals and institutions. Food choice is dynamic as it unfolds and is embedded in eating episodes over lifetimes within historical eras. Food choice is multilevel as physical, biological, psychological, and sociocultural factors operate simultaneously and interact. Food choice is integrated as people coordinate many considerations to construct specific eating activities. Food choice is diverse in its broad scope of distinct and unique eating activities. Food choice can be examined using both multi‐perspective and multi‐purpose approaches, and it may not be possible to integrate different perspectives into a unified approach to understanding and changing food choice.
From one host to another: tracking vector movements using microsatellite markers
Authors: Waite Jessica L.
Published: January 2014

In principle, the solution to stopping the spread of any vectorborne pathogen is a simple one – just stop infected vectors from biting new hosts and the pathogen cannot spread. Importantly, this does not necessarily require killing all vectors, or protecting all hosts. Transmission only occurs when an infected vector moves to a new host, and so knowing how vectors move between hosts in nature and how they choose hosts is crucial to understanding transmission. For example, the infection status of a potential vector or that of a potential host would have a huge influence on pathogen transmission if it affected vector movement or host choice. Remarkably little is known about how vectors move between and choose hosts in nature, in part because of the logistical difficulties of tracking vector movement. This is why the article by Levin and Parker () in this issue of Molecular Ecology is so exciting.
A tale of two lineages: unexpected, long‐term persistence of the amphibian‐killing fungus in Brazil
Authors: Lips Karen
Published: January 2014

For the past 17 years, scientists have been compiling a list of amphibian species susceptible to infection by the amphibian‐killing chytrid fungus, Batrachochytrium dendrobatidis (Bd), all over the world, with >500 species infected on every continent except Antarctica (Olson et al. ). Where Bd has been found, the impacts on amphibians has been one of two types: either Bd arrives into a naïve amphibian population followed by a mass die‐off and population declines (e.g. Lips et al. ), or Bd is present at some moderate prevalence, usually infecting many species but at apparently nonlethal intensities for a long time. In this issue of Molecular Ecology, Rodriguez et al. () discover that the Atlantic Coastal Forest of Brazil is home to two Bd lineages: the Global Pandemic Lineage (Bd‐GPL) – the strain responsible for mass die‐offs and population declines – and a lineage endemic to Brazil (Bd‐Bz). Even more surprising was that both lineages have been present in this area for the past 100 years, making these the oldest records of Bd infecting amphibians. The team also described a moderate but steady prevalence of ~20% across all sampled anuran families for over 100 years, indicating that Brazil has been in an enzootic disease state for over a century. Most amphibians were infected with Bd‐GPL, suggesting this lineage may be a better competitor than Bd‐Bz or may be replacing the Bd‐Bz lineage. Rodriguez et al. () also detected likely hybridization of the two Bd lineages, as originally described by Schloegel et al. ().
Capacity building in the health sector to improve care for child nutrition and development
Authors: Yousafzai Aisha K. , Rasheed Muneera A. , Daelmans Bernadette , Manji Sheila , Arnold Caroline , Lingam Raghu , Muskin Joshua , Lucas Jane E.
Published: January 2014

The effectiveness of interventions promoting healthy child growth and development depends upon the capacity of the health system to deliver a high‐quality intervention. However, few health workers are trained in providing integrated early child‐development services. Building capacity entails not only training the frontline worker, but also mobilizing knowledge and support to promote early child development across the health system. In this paper, we present the paradigm shift required to build effective partnerships between health workers and families in order to support children's health, growth, and development, the practical skills frontline health workers require to promote optimal caregiving, and the need for knowledge mobilization across multiple institutional levels to support frontline health workers. We present case studies illustrating challenges and success stories around capacity development. There is a need to galvanize increased commitment and resources to building capacity in health systems to deliver early child‐development services.
Promoting equity through integrated early child development and nutrition interventions
Authors: Black Maureen M. , Dewey Kathryn G.
Published: January 2014

Sustainable development, a foundation of the post‐2015 global agenda, depends on healthy and productive citizens. The origins of adult health begin early in life, stemming from genetic–environmental interactions that include adequate nutrition and opportunities for responsive learning. Inequities associated with inadequate nutrition and early learning opportunities can undermine children's health and development, thereby compromising their productivity and societal contributions. Transactional theory serves as a useful framework for examining the associations that link early child development and nutrition because it emphasizes the interplay that occurs between children and the environment, mediated through caregiver interactions. Although single interventions targeting early child development or nutrition can be effective, there is limited evidence on the development, implementation, evaluation, and scaling up of integrated interventions. This manuscript introduces a special edition of papers on six topics central to integrated child development/nutrition interventions: (1) review of integrated interventions; (2) methods and topics in designing integrated interventions; (3) economic considerations related to integrated interventions; (4) capacity‐building considerations; (5) examples of integrated interventions; and (6) policy implications of integrated interventions. Ensuring the health and development of infants and young children through integrated child development/nutrition interventions promotes equity, a critical component of sustainable development.
Cost effectiveness of responsive stimulation and nutrition interventions on early child development outcomes in Pakistan
Authors: Gowani Saima , Yousafzai Aisha K. , Armstrong Robert , Bhutta Zulfiqar A.
Published: January 2014

Early childhood programs are heralded as a way to improve children's health and educational outcomes. However, few studies in developing countries calculate the effectiveness of quality early childhood interventions. Even fewer estimate the associated costs of such interventions. The study here looks at the costs and effectiveness of a cluster‐randomized effectiveness trial on children from birth to 24 months in rural Sindh, Pakistan. Responsive stimulation and/or enhanced nutrition interventions were integrated in the Lady Health Worker program in Pakistan. Outcomes suggest that children who receive responsive stimulation had significantly better development outcomes at 24 months than those who only received enhanced nutrition intervention. A cost‐effectiveness analysis of the results verifies that early childhood interventions that include responsive stimulation are more cost effective than a nutrition intervention alone in promoting children's early development. Costs of a responsive stimulation intervention integrated in an existing community‐based service providing basic health and nutrition care is approximately US$4 per month per child. We discuss these findings and make recommendations about scaling up and costs for future early child development programs.
Marked changes in platelet count and function following pediatric congenital heart surgery
Authors: Bønding Andreasen Jo , Hvas Anne‐Mette , Ravn Hanne B.
Published: January 2014

Background

Reduced hemostatic capacity is common following congenital heart surgery using cardiopulmonary bypass (CPB). The etiology is multifactorial with dilutional coagulopathy, as well as platelet adhesion and activation in the CPB circuit and oxygenator. The purpose of the present study was to evaluate platelet count and function in children following CPB.

Methods

In a prospective, observational study comprising 40 children, platelet count and function (Multiplate Analyzer®) were measured before surgery, immediately after bypass, and on the first postoperative day. Furthermore, conventional coagulation analysis and thromboelastometry (ROTEM®) were carried out.

Results

A significant decrease in platelet count was observed immediately after coming of bypass (P < 0.001) and persisted to the first postoperative day (P = 0.002). Platelet function was reduced immediately after bypass after induction with ADP (P < 0.001) or TRAP (P = 0.03). The duration of CPB correlated significantly with the decrease in platelet count (r = −0.62, P = 0.0001) and reduction in platelet function (r = −0.42—0.63; P < 0.01). Moderate to deep hypothermia during CPB was associated with a decreased platelet function (P = 0.01–0.12), whereas cyanosis or previous heart surgery caused no further changes in platelet function following CPB.

Conclusion

Both platelet count and platelet function were significantly reduced after CPB in children undertaken correctional heart surgery. Duration of CPB and hypothermia was associated with significant changes in platelet function.
Effect of intranasal dexmedetomidine or oral midazolam premedication on sevoflurane EC50 for successful laryngeal mask airway placement in children: a randomized, double‐blind, placebo‐controlled trial
Authors: Savla Jyothi R. , Ghai Babita , Bansal Dipika , Wig Jyotsna
Published: January 2014

Introduction

This study was conducted to determine the effect of oral midazolam (OM) or intranasal dexmedetomidine (IND) on the EC50 of sevoflurane for successful laryngeal mask airway placement in children. We hypothesize that premedication with either agent might reduce the sevoflurane EC50 for laryngeal mask airway placement in children to a similar extent.

Methods

Fifty‐two American Society of Anesthesiologists (ASA) I children (aged 1–6 years) scheduled for general anesthesia with laryngeal mask airway were randomized to one of the three groups: group M received 0.5 mg·kg−1 OM with honey and intranasal saline, group D received 2 μg·kg−1 IND along with oral honey, and group P received oral honey and intranasal saline at least 30 min prior to induction of anesthesia. Anesthesia was induced with incremental sevoflurane up to 8% in 100% O2. A predetermined target endtidal sevoflurane (ETsevo) concentration (2% in the first child of all three groups) was sustained for 10 min before the attempt of laryngeal mask airway insertion by adjusting dial concentration. No intravenous anesthetic or neuromuscular blockade was used. ETsevo was increased/decreased (step size 0.2%) using Dixon's and Massey's up and down method in next patient depending upon previous patient's response. Placement of the laryngeal mask airway without movement, coughing, biting, or bucking was considered as successful. EC50 of sevoflurane was calculated as the average of the crossover midpoints in each group, which was further confirmed by probit analysis.

Results

The EC50 of sevoflurane for laryngeal mask airway placement after OM (1.66 ± 0.31) and IND (1.57 ± 0.14) premedications was significantly lower than the placebo group (2.00 ± 0.17, P < 0.0001). The EC95 (95% CI) derived from probit regression analysis was 2.34% (2.22–2.51%) with OM, 1.88% (1.77–2.04%) with IND, and 2.39% (2.25–2.35%) with placebo group.

Conclusions

Oral midazolam and IND premedications significantly reduce the sevoflurane EC50 for laryngeal mask airway insertion in children by 17% and 21%, respectively.
LESION SIMULATING DISEASE 1 and ENHANCED DISEASE SUSCEPTIBILITY 1 differentially regulate UV‐C‐induced photooxidative stress signalling and programmed cell death in Arabidopsis thaliana
Authors: WITUSZYŃSKA WERONIKA , SZECHYŃSKA‐HEBDA MAGDALENA , SOBCZAK MIROSŁAW , RUSACZONEK ANNA , KOZŁOWSKA‐MAKULSKA ANNA , WITOŃ DAMIAN , KARPIŃSKI STANISŁAW
Published: January 2014

As obligate photoautotrophs, plants are inevitably exposed to ultraviolet (UV) radiation. Because of stratospheric ozone depletion, UV has become more and more dangerous to the biosphere. Therefore, it is important to understand UV perception and signal transduction in plants. In the present study, we show that LESION SIMULATING DISEASE 1 (LSD1) and ENHANCED DISEASE SUSCEPTIBILITY 1 (EDS1) are antagonistic regulators of UV‐C‐induced programmed cell death (PCD) in Arabidopsis thaliana. This regulatory dependence is manifested by a complex deregulation of photosynthesis, reactive oxygen species homeostasis, antioxidative enzyme activity and UV‐responsive genes expression. We also prove that a UV‐C radiation episode triggers apoptotic‐like morphological changes within the mesophyll cells. Interestingly, chloroplasts are the first organelles that show features of UV‐C‐induced damage, which may indicate their primary role in PCD development. Moreover, we show that Arabidopsis Bax inhibitor 1 (AtBI1), which has been described as a negative regulator of plant PCD, is involved in LSD1‐dependent cell death in response to UV‐C. Our results imply that LSD1 and EDS1 regulate processes extinguishing excessive energy, reactive oxygen species formation and subsequent PCD in response to different stresses related to impaired electron transport.
Syndecan‐2 regulates melanin synthesis via protein kinase C βII‐mediated tyrosinase activation
Authors: Jung Hyejung , Chung Heesung , Chang Sung Eun , Choi Sora , Han Inn‐Oc , Kang Duk‐Hee , Oh Eok‐Soo
Published: January 2014

Syndecan‐2, a transmembrane heparan sulfate proteoglycan that is highly expressed in melanoma cells, regulates melanoma cell functions (e.g. migration). Since melanoma is a malignant tumor of melanocytes, which largely function to synthesize melanin, we investigated the possible involvement of syndecan‐2 in melanogenesis. Syndecan‐2 expression was increased in human skin melanoma tissues compared with normal skin. In both mouse and human melanoma cells, siRNA‐mediated knockdown of syndecan‐2 was associated with reduced melanin synthesis, whereas overexpression of syndecan‐2 increased melanin synthesis. Similar effects were also detected in human primary epidermal melanocytes. Syndecan‐2 expression did not affect the expression of tyrosinase, a key enzyme in melanin synthesis, but instead enhanced the enzymatic activity of tyrosinase by increasing the membrane and melanosome localization of its regulator, protein kinase CβII. Furthermore, UVB caused increased syndecan‐2 expression, and this up‐regulation of syndecan‐2 was required for UVB‐induced melanin synthesis. Taken together, these data suggest that syndecan‐2 regulates melanin synthesis and could be a potential therapeutic target for treating melanin‐associated diseases.
Molecular pathology of pancreatic cancer
Authors: Saiki Yuriko , Horii Akira
Published: January 2014

By genomic and epigenomic screening techniques, substantial progress has been made in our understanding of pancreatic cancer. The comprehensive studies of the pancreatic cancer genome have revealed that most genetic alterations are identified to be associated with specific core signaling pathways including high‐frequency mutated genes such as KRAS, CDKN2A, TP53, and SMAD4 along with several low‐frequency mutated genes. Three types of histological precursors of pancreatic cancer: pancreatic intraepithelial neoplasia, mucinous cystic neoplasm, and intraductal papillary mucinous neoplasm, had been recognized by morphological studies and the recent genomic screening techniques revealed that each of these precursor lesions were associated with specific molecular alterations. In the familial pancreatic cancer cases, several responsible genes were discovered. Epigenetic changes also play an important role in the progression of pancreatic cancer. Several tumor suppressor genes were silenced due to aberrant promoter CpG island hypermethylation. Several genetically engineered mouse models, based on the Kras mutation, were created, and provided reliable tools to identify the key molecules responsible for the development or progression of pancreatic cancer.
Combined high‐grade neuroendocrine carcinoma of the lung: Clinicopathological and immunohistochemical study of 34 surgically resected cases
Authors: Yamada Kenji , Maeshima Akiko Miyagi , Tsuta Koji , Tsuda Hitoshi
Published: January 2014

To understand the pathogenesis of high‐grade neuroendocrine carcinoma (HGNEC), we examined the histopathology and immunoreactivity against adenocarcinoma (AD), squamous cell carcinoma (SQ), and neuroendocrine markers in 34 cases with combined HGNEC. The 5 year overall survival rates of patients with combined small cell carcinoma (SCC) (n = 9) and combined large cell neuroendocrine carcinoma (LCNEC) (n = 25) were 33% and 75%, respectively (P = 0.011). Most of the patients were male (94%), smokers (94%), and had tumors located in the peripheral (94%) and upper lobe (65%) of the lung. Histopathologically, non‐HGNEC components were predominantly ADs (65%) followed by SQs (26%). In combined HGNEC and AD, a lepidic AD component was found in 12 cases (48%). For the HGNEC components of combined HGNEC and AD, the incidence of positivity of thyroid transcription factor‐1 (TTF‐1) (8G7G3/1) and TTF1 (SPT24) were 64% and 91%, respectively. For HGNEC components of combined HGNEC and SQ, the incidence of positivity of 34βE12 and p63 were 22% and 11%, respectively. In conclusion, 48% of combined HGNEC and AD cases had a lepidic AD component, suggesting that HGNEC can develop in association with pre‐existing AD. AD markers, but not SQ markers, were frequently retained through development of the HGNEC component.
The threat of root‐knot nematodes (Meloidogyne spp.) in Africa: a review
Authors: Onkendi E. M. , Kariuki G. M. , Marais M. , Moleleki L. N.
Published: January 2014

Meloidogyne species pose a significant threat to crop production in Africa due to the losses they cause in a wide range of agricultural crops. The direct and indirect damage caused by various Meloidogyne species results in delayed maturity, toppling, reduced yields and quality of crop produce, high costs of production and therefore loss of income. In addition, emergence of resistance‐breaking Meloidogyne species has partly rendered various pest management programmes already in place ineffective, therefore putting food security of the continent at risk. It is likely that more losses may be experienced in the future due to the on‐going withdrawal of nematicides. To adequately address the threat of Meloidogyne species in Africa, an accurate assessment and understanding of the species present, genetic diversity, population structure, parasitism mechanisms and how each of these factors contribute to the overall threat posed by Meloidogyne species is important. Thus, the ability to accurately characterize and identify Meloidogyne species is crucial if the threat of Meloidogyne species to crop production in Africa is to be effectively tackled. This review discusses the use of traditional versus molecular‐based identification methods of Meloidogyne species and how accurate identification using a polyphasic approach can negate the eminent threat of root knot nematodes in crop production. The potential threat to Africa posed by highly damaging and resistance‐breaking populations of ‘emerging’ Meloidogyne species is also examined.
Analysis of resistance to witches’ broom disease (Moniliophthora perniciosa) in flower cushions of Theobroma cacao in a segregating population
Authors: Silva D. V. , Araújo I. S. , Branco S. M. J. , Aguilar‐Vildoso C. I. , Lopes U. V. , Marelli J. P. , Motamayor J. C. , Royaert S. , Rebouças R. C. , Corrêa R. X.
Published: January 2014

This study evaluates resistance to witches’ broom disease in flower cushions of Theobroma cacao under field conditions. The aim was to determine optimal inoculation methods to evaluate the disease incidence using flower cushions in the field. A segregating mapping population of 580 trees (cultivar TSH 1188 × CCN 51) was analysed under two field conditions: high and low inoculum levels (in different years), corresponding respectively to trees with or without dried witches’ brooms hanging on the trees and producing basidiocarps. The number of newly formed cushion brooms in each tree was counted by the conventional method, and also the healthy and infected flower cushions in three 30 cm‐long regions along the trunk and the two main branches. The field inoculation methods discriminated between genotypes, with a 26% increase in disease incidence by Moniliophthora perniciosa at high inoculum. Two different segregation patterns were also observed: 27:27:9:1 under low, and 27:9:9:9:3:3:3:1 under high inoculum potential. It was also determined that at least 20 flower cushions were needed to accurately determine the percentage of infection. These methodologies allowed identification of the extreme phenotypes in this mapping population, and can therefore facilitate the detection of sources of resistance to witches’ broom disease.