bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uneven implementation of the National Perinatal Depression Initiative: findings from a survey of Australian women's hospitals
Authors: Fisher Jane , Chatham Elizabeth , Haseler Sally , McGaw Beth , Thompson Jane 
Published: October 2012

BackgroundAustralia is a leader in recognising that perinatal mental health problems are prevalent and constitute a significant burden of disease among women. In 2009, the Australian government launched the National Perinatal Depression Initiative (NPDI) to address this.AimsTo investigate implementation of Australia's NPDI.Materials and MethodsData were collected by a structured online survey assessing: screening for depression and depression risk in women receiving antenatal and postnatal care; staff training about perinatal depression; barriers and enablers to implementing the NPDI recommendations. All Australian members of Women's Healthcare Australasia (WHA) were invited to complete the survey in March 2011.ResultsOf 30 Australian WHA members, 14 (46.6%) completed the survey. The sample included a representative distribution of small, medium and large hospitals. All respondents had introduced some NPDI recommendations. Most (80%) reported using the Edinburgh Postnatal Depression Scale (EPDS) to screen for antenatal depression and for risk of developing depression but at varied gestational ages, and with differing cut‐off scores for follow‐up or referral. Only one assessed depression status postpartum. Responsibility for screening and feedback was predominantly assigned to midwives, most of whom were offered <4 h training. Implementation barriers included insufficient personnel; per‐client time requirements; insufficient clarity about screening protocols; difficulties modifying the medical record; few referral options and a lack of training resources.ConclusionsImplementation of the NPDI is uneven among Australian maternity hospitals. Little is known about perinatal mental health screening practices in the private sector and hospitals with <1000 births annually.
Patterns of weight gain in pregnant women with and without gestational diabetes mellitus: An observational study
Authors: Stewart Zoe A. , Wallace Euan M. , Allan Carolyn A. 
Published: October 2012

ObjectiveTo quantify late‐pregnancy weight gain in women with and without gestational diabetes mellitus (GDM) and to determine factors associated with gestational weight gain.Study designA prospective clinical audit of 212 women (115 GDM and 97 non‐GDM) who were weighed at each antenatal visit from 24–32 weeks gestation until delivery. Women received routine antenatal clinical care. For women with GDM, this included a 2‐h lifestyle counselling session, capillary blood glucose testing and frequent clinical review.ResultsWomen with GDM gained less weight than nondiabetic women (GDM: 1.18 kg (1.6%) [range, 3.8–7.1 kg]; non‐GDM: 4.0 kg (4.8%) [range, 0.7–18.5 kg]; P < 0.0001). Weight gain was influenced by body mass index and country of birth. Women with GDM showed reduced weight gain at weeks 1–4 postrecruitment, relative to weeks 4–8 (0.04 kg/week vs 0.45 kg/week; P < 0.0001). Nondiabetic women gained weight at a constant rate. GDM status was the only independent predictor of postrecruitment weight gain.ConclusionsApplication of a model of care for GDM (lifestyle advice and regular clinical review, in addition to home glucose monitoring) may reduce weight gain in women with GDM. The potential for applying a modified version of this model to all women in pregnancy warrants further study.
HPV vaccination of adult women: An audit of Australian general practitioners
Authors: Mazza Danielle , Petrovic Katja , Chakraborty Samantha 
Published: October 2012

BackgroundWhile initial Human Papillomavirus (HPV) vaccine uptake estimates are encouraging, especially in the school‐aged population, it is unclear to what extent general practitioners (GPs) have been recommending and administering the vaccine to adult women and what the uptake has been.MethodsA mixed methods study of Australian GPs consisting of a knowledge and attitudes questionnaire and an audit which assessed overall vaccination rates since commencement of the Australian National HPV program and in the last 50 female patients aged 27–45 years who consulted them.ResultsGPs have a good level of knowledge regarding HPV vaccination and are strongly committed to it for women until 27 years but are much less so for women aged 27–45 years. From 2007 to 2010, only 1.9% of women aged 27–45 who consulted the GPs commenced HPV vaccination. Of those, however, the majority completed all three doses. Higher rates of commencement of HPV vaccination (11.4%) were demonstrated by auditing the last 50 consecutive patients seen by the GP. In this group of women, 63% had received a Pap test in the last two years. Female GPs had significantly higher rates of vaccination.ConclusionsThere is relatively low HPV vaccine uptake in women aged 27–45. Once HPV vaccination is commenced, however, completion rates are high in women in this age group. Low uptake may be due to lack of opportunistic awareness raising in relevant consultations. Clear guidance together with further exploration of patient factors and GP barriers and enablers would assist implementation of HPV vaccination.
Asthma phenotypes identified by latent class analysis in the ISAAC phase II Spain study
Authors: Weinmayr G. , Keller F. , Kleiner A. , du Prel J. B. , Garcia‐Marcos L. , Batllés‐Garrido J. , Garcia‐Hernandez G. , Suarez‐Varela M. M. , Strachan D. P. , Nagel G. 
Published: October 2012

SummaryBackgroundClassification of respiratory symptoms may help to identify different underlying asthma phenotypes reflecting differences in aetiology and prognosis of wheezing disease among children.ObjectiveTo determine childhood asthma phenotypes based on respiratory symptoms from a widely used questionnaire to further classify phenotypes in international settings.MethodsBetween 2000 and 2002 cross‐sectional studies were performed in four centres in Spain. Parental questionnaires were used to collect information on allergic diseases in more than 4000 children aged 8–12 years. In addition, objective markers for allergic sensitization and bronchial hyperresponsiveness (BHR) were measured. Latent class analyses (LCA) were applied to identify subgroups of children according to respiratory symptoms, and then the association of these groups with relevant clinical features such as concomitant allergic disease symptoms, atopy and BHR was studied.ResultsWe found seven classes, one corresponding to healthy children, three classes related to wheeze and three other classes mainly related to congestion and coughed‐up phlegm. These tentative phenotypes differed in severity of symptoms and also in clinical correlates such as BHR and allergic sensitization. Atopy was more predominant in the ‘wheeze phenotypes’ whereas concomitant ‘allergic’ symptoms were most frequent in two of the ‘wheeze phenotypes’ and one of the ‘cough phenotypes’.ConclusionsLCA on reported symptoms in a cross‐sectional survey allowed different subgroups with meaningful clinical correlates to be defined. It remains to be investigated to what extent these groups also have different aetiologies, prognoses and therapeutic needs.
Down syndrome and personalized medicine: Changing paradigms from genotype to phenotype to treatment
Authors: McCabe Linda L. , McCabe Edward R. B. 
Published: October 2012

Abstract Personalized Medicine represents a paradigm shift in the conceptual framework of research and clinical care. This shift argues that Down syndrome is a treatable condition, and therefore we must invest in research to improve outcomes. Individuals with Down syndrome have varying levels of increased risk for a number of co‐morbidities, including infantile spasms and early onset Alzheimer's disease. We will review research in these associated conditions to show how investigators are attempting to identify biomarkers, including genomic, epigenomic, proteomic and metabolomic “signatures” that will predict who may be at risk to develop a specific co‐morbidity prior to onset and will provide novel targets for therapeutic development. This Personalized Medicine approach will permit predictive and preventive approaches for individuals at increased risk for co‐morbidities. The support for clinical trials among individuals with Down syndrome is beginning to overcome the “culture of intractability” that has surrounded this disorder.
Functional analysis of ectodermal β‐catenin during external genitalia formation
Authors: Mazahery Ahmad Reza , Suzuki Kentaro , Nagafuchi Akira , Miyajima Masayasu , Nakagata Naomi , Orvis Grant D. , Behringer Richard R. , Yamada Gen 
Published: October 2012

Abstract β‐catenin is a molecule belonging to the armadillo family of proteins that is a crucial core‐component of cellular adherens junctions, and a component of the canonical Wnt‐signaling pathway. We attempted to analyze the functional significance of ectodermal‐derived β‐catenin during the development of the mouse genital tubercle, a mammalian anlage of the external genitalia. For this purpose, the conditional loss of function mouse mutant Wnt7a‐Cre;β‐catf/f was utilized. Loss of ectodermal β‐catenin leads to the formation of urethral cleft during preputial uprising. Although expression of E‐cadherin was retained in the genital tubercle ectoderm of mutants, probably through plakoglobin compensatory expression, expression of other crucial adherens junction components such as α‐catenin and F‐actin in the cell‐cell border were distinctly reduced. We also showed that β‐catenin is necessary for the expression of its transcriptional downstream target Lef‐1 which was localized in the basal layer of the preputial ectoderm, excluding the midventral region at E15.5. Such specialized region was observed to possess cytoplasmic β‐catenin expression at this stage. Coincidentally, mitotically active cells were also found in the basal layer of the preputial ectoderm excluding the midventral region. In mutant genital tubercle, cell proliferation in the preputial ectoderm was decreased. Taken together, we suggest that ectodermal β‐catenin is necessary not only to maintain adherens junction integrity, but also to regulate cell proliferation possibly through Lef‐1 functions. Thus, β‐catenin is shown to perform dual functions, initially as an adhesion molecule and later on as a possible transcription factor.
Interferential therapy: a new treatment for slow transit constipation. A pilot study in adults
Authors: Queralto M. , Vitton V. , Bouvier M. , Abysique A. , Portier G. 
Published: October 2012

AbstractAimThe study aimed to assess, for the first time, the effectiveness of interferential therapy (IFT) in the treatment of slow transit constipation in adults and its impact on the quality of life.MethodAll consecutive patients with slow transit constipation diagnosed by symptomology and a colonic transit time (CTT) of > 100 h measured with radiopaque markers were included in this prospective study. IFT was performed for 1 h/day over 3 months. Clinical improvement was based on the stool diary and the Knowles–Eccersley–Scott Symptom and Cleveland Clinic Constipation Scores. Quality of life was assessed with the Gastrointestinal Quality of Life Index questionnaire.ResultsEleven patients with a median age of 51 years were included. At the end of the follow‐up period, seven (63.6%) had significantly improved after IFT with a median of 0.66 stools per week [interquartile range (IQR) 0.33–0.66] before treatment and 1.66 (IQR 1.33–1.66) after (P = 0.007). The Knowles–Eccersley–Scott Symptom score changed from 30 (IQR 27–33) before treatment to 19 (IQR 17–26) after treatment (P = 0.005) and the Cleveland Clinic Constipation Score from 26 (IQR 25–28) to 17 (IQR 13–24; P = 0.005). The CTT improved from 103 h (IQR 101–113) to 98 h (IQR 94–107; P = 0.02). The Gastrointestinal Quality of Life Index score improved from 60 (IQR 57–63) to 95 (IQR 68–100; P = 0.005).ConclusionIFT is a new non‐invasive treatment for slow transit constipation. Further studies to confirm these results with longer follow‐up are necessary.
Predictors of hemoglobin response to eculizumab therapy in paroxysmal nocturnal hemoglobinuria
Authors: DeZern Amy E. , Dorr Donna , Brodsky Robert A. 
Published: October 2012

AbstractBackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a clonal, hematopoietic stem cell disorder that manifests with hemolytic anemia and bone marrow failure. Eculizumab has been shown to improve anemia, decrease intravascular hemolysis, and reduce the risk of thrombosis.Design and methodsThis is a retrospective, single‐center study of patients treated with eculizumab and categorized according to response criteria. Complete response (CR) was defined as transfusion independence with normal hemoglobin for age/sex, absence of symptoms, and lactate dehydrogenase <1.5 times the upper limit of normal. A good partial response (GPR) was defined as decreased transfusions from pretreatment and lactate dehydrogenase <1.5 upper limit of normal without thrombosis. These patients did not achieve normal hemoglobins for age and sex. A suboptimal response was defined as unchanged transfusion needs and persistent of symptoms.ResultsThirty patients with PNH clones were treated with eculizumab and classified as complete responders (four patients), good partial responders (16), and suboptimal responders (10) over 863 patient‐months of treatment. Complete responders had a decrease in red cell clone size, while good partial responders had an increase. Thirteen patients treated did not meet inclusion criteria for the clinical trials of eculizumab due to lack of transfusions or thrombocytopenia; eight had at least a GPR.ConclusionsEculizumab is efficacious in patients with PNH, but responses can vary and may depend on underlying marrow failure, underlying inflammatory conditions and red cell clone size following treatment. Normalization of hemoglobin with decrease in red cell clone size may predict CR.
Plasticity in transmission strategies of the malaria parasite, Plasmodium chabaudi: environmental and genetic effects
Authors: Cameron Angus , Reece Sarah E. , Drew Damien R. , Haydon Daniel T. , Yates Andrew J. 
Published: October 2012

AbstractParasites may alter their behaviour to cope with changes in the within‐host environment. In particular, investment in transmission may alter in response to the availability of parasite resources or host immune responses. However, experimental and theoretical studies have drawn conflicting conclusions regarding parasites' optimal (adaptive) responses to deterioration in habitat quality. We analyse data from acute infections with six genotypes of the rodent malaria species Plasmodium chabaudi to quantify how investment in transmission (gametocytes) is influenced by the within‐host environment. Using a minimum of modelling assumptions, we find that proportional investment in gametocytogenesis increases sharply with host anaemia and also increases at low parasite densities. Further, stronger dependence of investment on parasite density is associated with greater virulence of the parasite genotype. Our study provides a robust quantitative framework for studying parasites' responses to the host environment and whether these responses are adaptive, which is crucial for predicting the short‐term and evolutionary impact of transmission‐blocking treatments for parasitic diseases.
Recovery of a nearly extinct Galápagos tortoise despite minimal genetic variation
Authors: Milinkovitch Michel C. , Kanitz Ricardo , Tiedemann Ralph , Tapia Washington , Llerena Fausto , Caccone Adalgisa , Gibbs James P. , Powell Jeffrey R. 
Published: October 2012

AbstractA species of Galápagos tortoise endemic to Española Island was reduced to just 12 females and three males that have been bred in captivity since 1971 and have produced over 1700 offspring now repatriated to the island. Our molecular genetic analyses of juveniles repatriated to and surviving on the island indicate that none of the tortoises sampled in 1994 had hatched on the island versus 3% in 2004 and 24% in 2007, which demonstrates substantial and increasing reproduction in situ once again. This recovery occurred despite the parental population having an estimated effective population size <8 due to a combination of unequal reproductive success of the breeders and nonrandom mating in captivity. These results provide guidelines for adapting breeding regimes in the parental captive population and decreasing inbreeding in the repatriated population. Using simple morphological data scored on the sampled animals, we also show that a strongly heterogeneous distribution of tortoise sizes on Española Island observed today is due to a large variance in the number of animals included in yearly repatriation events performed in the last 40 years. Our study reveals that, at least in the short run, some endangered species can recover dramatically despite a lack of genetic variation and irregular repatriation efforts.
Introducing the patient's perspective in hospital health technology assessment (HTA): the views of HTA producers, hospital managers and patients
Authors: Gagnon Marie‐Pierre , Desmartis Marie , Gagnon Johanne , St‐Pierre Michèle , Gauvin François‐Pierre , Rhainds Marc , Lepage‐Savary Dolorès , Coulombe Martin , Dipankui Mylène Tantchou , Légaré France 
Published: October 2012

AbstractBackgroundThe recent establishment of health technology assessment (HTA) units in University hospitals in the Province of Quebec (Canada) provides a unique opportunity to foster increased participation of patients in decisions regarding health technologies and interventions at the local level. However, little is known about factors that influence whether the patient's perspective is taken into consideration when such decisions are made.ObjectiveTo explore the practices, perceptions and views of the various HTA stakeholders concerning patient involvement in HTA at the local level.MethodData were collected using semi‐structured interviews with 24 HTA producers and hospital managers and two focus groups with a total of 13 patient representatives.ResultsPatient representatives generally showed considerable interest in being involved in HTA. Our findings support the hypothesis that the patient perspective contributes to a more accurate and contextualized assessment of health technologies and produces HTA reports that are more useful for decision makers. They also suggest that participation throughout the assessment process could empower patients and improve their knowledge. Barriers to patient involvement in HTA at the local level are also discussed as well as potential strategies to overcome them.Discussion and conclusionThis study contributes to knowledge that could guide interventions in favour of patient participation in HTA activities at the local level. Experimenting with different patient involvement strategies and assessing their impact is needed to provide evidence that will inform future interventions of this kind.
Piecing together the family portrait of TCR‐CD3 complexes
Authors: Kuhns Michael S. , Badgandi Hemant B. 
Published: October 2012

SummaryThe pre‐T‐cell receptor (TCR)‐, αβTCR‐, and γδTCR‐CD3 complexes are members of a family of modular biosensors that are responsible for driving T‐cell development, activation, and effector functions. They inform essential checkpoint decisions by relaying key information from their ligand‐binding modules (TCRs) to their signaling modules (CD3γε + CD3δε and CD3ζζ) and on to the intracellular signaling apparatus. Their actions shape the T‐cell repertoire, as well as T‐cell‐mediated immunity; yet, the mechanisms that underlie their activity remain an enigma. As with any molecular machine, understanding how they function depends upon understanding how their parts fit and work together. In the 30 years since the initial biochemical and genetic characterizations of the αβTCR, the structure and function of the individual components of these family members have been extensively characterized. Cumulatively, this information has allowed us to piece together a portrait of the αβTCR‐CD3 complex and outline the form of the remaining family members. Here we review the known structural and functional characteristics of the components of these TCR‐CD3 complex family members. We then discuss how these data have informed our understanding of the architecture of the αβTCR‐CD3 complex as well as their implications for the other family members. The intent is to provide a framework for considering: (i) how these thematically similar complexes diverge to execute their specific functions and (ii) how our knowledge of the form and function of these distinct family members can cross‐inform our understanding of the other family members.
Structural insights into key sites of vulnerability on HIV‐1 Env and influenza HA
Authors: Julien Jean‐Philippe , Lee Peter S. , Wilson Ian A. 
Published: October 2012

SummaryHuman immunodeficiency virus‐1 (HIV‐1) envelope protein (Env) and influenza hemagglutinin (HA) are the surface glycoproteins responsible for viral entry into host cells, the first step in the virus life cycle necessary to initiate infection. These glycoproteins exhibit a high degree of sequence variability and glycosylation, which are used as strategies to escape host immune responses. Nonetheless, antibodies with broadly neutralizing activity against these viruses have been isolated that have managed to overcome these barriers. Here, we review recent advances in the structural characterization of these antibodies with their viral antigens that defines a few sites of vulnerability on these viral spikes. These broadly neutralizing antibodies tend to focus their recognition on the sites of similar function between the two viruses: the receptor‐binding site and membrane fusion machinery. However, some sites of recognition are unique to the virus neutralized, such as the dense shield of oligomannose carbohydrates on HIV‐1 Env. These observations are discussed in the context of structure‐based design strategies to aid in vaccine design or development of antivirals.
Non‐catalytic tyrosine‐phosphorylated receptors
Authors: Dushek Omer , Goyette Jesse , van der Merwe P. Anton 
Published: October 2012

SummaryLeukocytes play a critical role in recognizing and responding to infection and cancer. Central to this function is an array of cell‐surface receptors that lack sequence homology. Many of these receptors have in common the fact that their signaling involves phosphorylation of cytoplasmic domains by extrinsic tyrosine kinases. These non‐catalytic tyrosine‐phosphorylated receptors (NTRs) share a number of other features, including small size and optimal stimulation by surface–associated ligands. We argue here that NTRs are also likely to share the same kinetic‐segregation triggering mechanism, which involves segregation of the engaged NTR from receptor tyrosine phosphatases with large ectodomains such as CD45 and CD148. NTRs signal through tyrosine‐containing cytoplasmic motifs, which recruit distinct cytoplasmic signaling proteins when phosphorylated, transducing activatory or inhibitory signals. They have two features that make them uniquely well suited to their role in immune recognition of infection and cancer. Their modular structure enables the coupling of many rapidly evolving receptors with diverse ligand specificities to the same conserved signaling machinery. Their similarity in size and shared signaling machinery enables them to colocalize at cell‐cell interfaces when they engage ligands, facilitating the integration of activatory and inhibitory signals from multiple receptors at the cell surface.