bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome
Authors: Kim H. S. , Lee T.‐Y. , Kim E. Y. , Choi J. H. , Kim S. Y. , Hwang Y.‐C. , Kang J.‐H. , Ahn K. J. , Chung H. Y. , Jeong I.‐K. 
Published: February 2012

Diabet. Med. 29, 1335–1338 (2012)AbstractFulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA1c (< 69 mmol/mol, 8.5%), (3) rapid progression to diabetic ketoacidosis, (4) very low C‐peptide level, and (5) often associated with elevated serum pancreatic enzymes, and absence of diabetes‐related autoantibodies. We encountered a case of fulminant Type 1 diabetes that developed with an initial manifestation of the insulin autoimmune syndrome and rapidly progressed to diabetic ketoacidosis during pregnancy. A 31‐year‐old Korean woman presented with recurrent sudden onset of sweating and change of consciousness during sleep at 19 weeks gestation. During a 72‐h fasting test, hypoglycaemia (1.72 mmol/l) occurred at 4 h after the start of the test. At that time, there was a high insulin level (370.2 μU/ml), a paradoxically low C‐peptide level (0.01 nmol/l) and a positive insulin autoantibody test. An oral glucose tolerance test revealed postprandial hyperglycaemia. She was initially diagnosed as the insulin autoimmune syndrome. On the day 5 of admission, she developed diabetic ketoacidosis. Her HbA1c was 62 mmol/mol (7.8%). The rapid progression of diabetic ketoacidosis altered the diagnosis to fulminant Type 1 diabetes. This case differed from typical fulminant Type 1 diabetes because it presented with hypoglycaemia, and positive insulin and anti‐phospholipid antibody tests. Her HLA typing was HLA‐DQA1*0302, 0501, HLA‐DRB1*0301 (DR3), 0901(DR9). Her glucose level was subsequently very well controlled with multiple insulin injections and she successfully delivered a healthy baby.
Implementing treatment goals for successful long‐term management of psoriasis
Authors: Mrowietz U. 
Published: February 2012

AbstractTreatment goals are commonly used throughout medicine to ensure efficacious therapy of diseases and to prevent complications related to uncontrolled disease activity, such as the management of hypertension and diabetes. Psoriasis is a systemic immune‐mediated inflammatory disease comprising characteristic skin manifestations. A range of co‐morbidities has been associated with it, including diabetes and cardiovascular diseases such as myocardial infarction (MI) and stroke. There is good evidence that the severity of skin symptoms is related to mortality associated with MI. Therefore, long‐term efficacious control of skin inflammation is the treatment paradigm of choice, particularly in patients with severe skin involvement. Surveys in a number of countries have revealed a substantial under‐treatment of patients with moderate‐to‐severe psoriasis, leaving a considerable proportion without adequate disease control. In addition, a high number of patients were not satisfied with their treatment, including the time they needed to allocate for skin therapy and the number of visits to physicians. Therefore, the use of effective therapies is necessary to achieve appropriate control of inflammation and to improve patient satisfaction. The definition of treatment goals is an appropriate instrument for raising the quality of care and sets therapeutic standards in addition to evidence‐based guidelines. Consensus treatment goals for moderate‐to‐severe psoriasis were recently defined, and a treatment goal algorithm was developed through a Delphi process by a group of experts from 19 European countries. These have since been adopted into the update of the German S3 guidelines for treatment of psoriasis. Furthermore, a novel analysis was carried out on published Phase 3 clinical trial data from three studies of adalimumab therapy in psoriasis, which used the consented definition of moderate‐to‐severe disease and the proposed treatment goal algorithm. The data showed that the ‘treatment goal’ was achieved in 68.2–79.3% of the patients treated with adalimumab by week 16, with >93% achieving ‘treatment success’ (a ≥75 reduction in psoriasis area and severity index compared with baseline). These results were similar to those achieved using the protocol‐specified definitions of disease severity. Regular assessment of treatment goals during maintenance phase at intervals recommended by the published guidelines, such as 16 weeks for adalimumab, will ensure efficacious therapy over time. This may, consequently, represent progress towards establishing a standard of care for psoriasis.
Enamel hypoplasia in molars of sheep and goats, and its relationship to the pattern of tooth crown growth
Authors: Kierdorf H. , Witzel C. , Upex B. , Dobney K. , Kierdorf U. 
Published: February 2012

AbstractEnamel is the most highly mineralized and durable tissue of the mammalian body. As enamel does not undergo remodeling or repair, disturbances of enamel formation leave a permanent record in the tissue that can be used for life history reconstruction. This study reports light and scanning electron microscope findings on hypoplastic enamel defects, and on the chronology of crown growth in the molars of sheep and goats. A marked reduction of enamel extension rates in cervical compared with more cuspal crown portions of sheep and goat molars was recorded, with formation of the cervical 25% of the crown taking about the same time as that of the upper 75% of the crown. This explains the more frequent occurrence of enamel hypoplasia in cervical compared with upper and middle crown portions. Regarding the identification of hypoplastic enamel defects by external inspection, our results suggest a dependence on the type of defect and the associated presence of smaller or larger amounts of coronal cementum. Defects considered to reflect a slight to moderate impairment of secretory ameloblast function can normally be correctly diagnosed as they are not occluded by thick layers of cementum. In contrast, defects denoting a severe impairment of enamel matrix secretion can typically not be correctly identified because they are occluded by large amounts of cementum, so that neither depth nor extension of the defects can be assessed on external inspection. In these cases, microscopic analysis of tooth sections is required for a correct diagnosis of the hypoplastic enamel defects.
Modelling changes in the distribution of the critical food resources of a specialist folivore in response to climate change
Authors: Adams‐Hosking Christine , McAlpine Clive , Rhodes Jonathan R. , Grantham Hedley S. , Moss Patrick T. 
Published: February 2012

AbstractAim An important consideration when planning to conserve a species under climate change is to understand how the distribution of its food resources may also contract or shift under those same climatic conditions. Here, we use a case study to demonstrate a spatial conservation planning approach to inform decisions about where, under climate change, to protect and restore critical food and habitat resources for highly specialized species.Location Eastern Australia.Methods We developed fitted models for the koala (Phascolarctos cinereus) and five of its key eucalypt food trees using the maximum entropy algorithm available in Maxent. We then projected these models using a range of IPCC A1FI climate change scenarios and identified areas with a higher probability of occurrence. We calculated where the koala and its food trees may co‐occur under future climate change.Results The koala and its food trees experienced significant range contractions as climate change progressed, sometimes to regions outside their current distributions. The inland speciesEucalyptus camaldulensisandEucalyptus coolabahcontracted from the more arid interior, which is outside the koala range, but persisted in the eastern regions of the koala’s range, whileEucalyptus viminalis,Eucalyptus populneaandEucalyptus tereticorniscontracted eastwards and southwards, with a fragmented distribution. The highest probabilities of overlap between koalas and their food trees were identified in fragmented coastal and southern regions of the koala’s current range.Main conclusions The application of a robust species distribution modelling decision support tool identified important changes, under climate change, in the distribution of a specialist species and its key food trees. These distributions did not change in complete synergy and therefore areas of overlap varied, depending on the food tree species modelled. This is of particular importance in a conservation planning context, when considering targeted protection and restoration of species‐specific habitat resources.
Computer‐assisted assessment of obsessive‐compulsive disorder in young people: a preliminary evaluation of the Development and Well‐Being Assessment
Authors: Krebs Georgina , Liang Holan , Hilton Kristina , Macdiarmid Fiona , Heyman Isobel 
Published: February 2012

BackgroundPaediatric obsessive‐compulsive disorder (OCD) often goes undetected, delaying access to evidence‐based treatment. This study aimed to assess the utility of a computerised diagnostic tool, the Development and Well‐Being Assessment (DAWBA), in detecting OCD and comorbidity in youth.MethodA total of 51 young people referred to a specialist OCD service between September 2007 and July 2008 completed the DAWBA prior to clinical assessment. Computer‐rated and clinician‐rated DAWBA diagnoses were compared with those assigned by the specialist clinic.ResultsThe computer‐rated and clinician‐rated DAWBA correctly classified OCD in 71% and 77% of cases respectively. Compared to consensus diagnoses, the computer‐rated DAWBA tended to over‐diagnose comorbidity, while the clinician‐rated DAWBA diagnoses of comorbidity corresponded well with the consensus.ConclusionsThe DAWBA has potential value in detecting OCD as well as comorbid disorders, and could be a cost‐effective method for diagnosing OCD and related problems.
Effects of sertindole on cognition in clozapine‐treated schizophrenia patients
Authors: Nielsen R. E. , Levander S. , Thode D. , Nielsen J. 
Published: February 2012

Nielsen RE, Levander S, Thode D, Nielsen J. Effects of sertindole on cognition in clozapine‐treated schizophrenia patients.Objective:  To assess the cognitive effects of sertindole augmentation in clozapine‐treated patients diagnosed with schizophrenia. Cognition is secondary outcome of the trial.Method:  A 12‐week, double‐blinded, randomized, placebo‐controlled, augmentation study of patients treated with clozapine. Participants were randomized 1:1 to receive 16 mg of sertindole or placebo as adjunctive treatment to clozapine.Results:  Participants displayed substantial cognitive deficits, ranging from 1.6 standard deviation below norms at baseline to more than three standard deviations on tests of response readiness and focused attention. There were no significant differences between sertindole augmentation and placebo groups at study end. Correlation analysis of Positive and Negative Syndrome (PANSS) subscales, Global Assessment of Functioning subscale (GAF‐F) and Clinical Global Impression (CGI) with 20 neurocognitive indices was conducted, but no significant correlations were found. Second, we tested change from baseline to endpoint for the PANSS, GAF‐F, and CGI, vs. the concomitant changes in cognitive test performance, and found no significant correlations.Conclusion:  The clozapine‐treated patients displayed marked cognitive deficits at baseline. Adding sertindole did not improve or worsen cognitive functioning, which is in line with previous negative studies of the effect on cognition of augmenting clozapine treatment with another antipsychotic drug.
Arabidopsis Plants Having Defects in Nonsense‐mediated mRNA Decay Factors UPF1, UPF2, and UPF3 Show Photoperiod‐dependent Phenotypes in Development and Stress Responses
Authors: Shi Chuan , Baldwin Ian T. , Wu Jianqiang 
Published: February 2012

AbstractNonsense‐mediated mRNA decay (NMD) is an important mRNA quality surveillance pathway in all eukaryotes that eliminates aberrant mRNAs derived from various sources. Three NMD factor proteins, UPF1, UPF2, and UPF3 are required for the NMD process and were found to be also involved in certain stress responses in mammalian and yeast cells. Using Arabidopsis thaliana mutants of UPF1 and UPF3 and UPF2‐silenced lines (irUPF2), we examined the involvement of UPF1, UPF2, and UPF3 in development and in response to stresses, wounding and infection by Pseudomonas syringae pv. tomato strain DC3000. Under the long (16 h) photoperiod condition, Arabidopsis having a defect in NMD factors exhibited altered morphologies of various organs, disturbed homeostasis of wounding‐induced jasmonic acid and pathogen‐elicited salicylic acid, and abnormal wounding‐ and methyl jasmonate‐induced changes in the transcript levels of two defense‐related genes, LOX2 and VSP2. Importantly, when plants were cultivated under the short (10 h) photoperiod condition, mutants of UPF1 and UPF3 and irUPF2 showed smaller differences from the wild‐type plants in growth and stress‐induced responses. These data suggest a complex regulatory network, likely composed of light signaling and NMD factor‐mediated pathways, in influencing plant development and adaption to environmental stresses.
Electrophysiological determinants of arrhythmic susceptibility upon endocardial and epicardial pacing in guinea‐pig heart
Authors: Osadchii O. E. 
Published: February 2012

AbstractAimEndocardial pacing instituted to treat symptomatic bradycardia may nevertheless promote tachyarrhythmia in some pacemaker‐implanted patients. We sought to determine the contributing electrophysiological mechanisms.MethodsLeft ventricular (LV) monophasic action potential duration (APD90) and effective refractory periods were determined in perfused guinea‐pig hearts along with volume‐conducted ECG recordings during epicardial and endocardial stimulations.ResultsConsistent with electrotonic modulation of repolarization, APD90 at a given (either epicardial or endocardial) recording site tended to be longer while pacing from the ipsilateral LV site as compared to stimulations applied at the opposite side of ventricular wall. As a result, the intrinsic transmural repolarization gradient was amplified during endocardial pacing while being significantly reduced upon epicardial stimulations. The maximum slope of APD90 restitution was greater upon endocardial than epicardial pacing. The excitability was found to recur at earlier repolarization time point at endocardium than epicardium, thereby contributing to increased endocardial critical intervals for re‐excitation. Premature extrasystolic beats could have been elicited at shorter coupling stimulation intervals and propagated with greater transmural conduction delay upon endocardial than epicardial stimulations. Endocardial site exhibited lower ventricular fibrillation thresholds and greater inducibility of tachyarrhythmia upon extrasystolic stimulations as compared to epicardium.ConclusionArrhythmic susceptibility in guinea‐pig heart is greater during endocardial than epicardial pacing because of greater transmural APD90 dispersion, steeper electrical restitution slopes, greater critical intervals for LV re‐excitation and slower transmural conduction of the earliest premature ectopic beats. Further studies are warranted to determine whether these effects may contribute to proarrhythmia in paced human patients.
Emergence of Proteus mirabilis Harboring
bla
KPC-2
and
qnrD
in a Chinese Hospital
Authors: Hu Yan-yan , Cai Jia-chang , Zhang Rong , Zhou Hong-wei , Sun Qian , Chen Gong-xiang 
Published: February 2012

ABSTRACT

Nineteen carbapenem-nonsusceptible
Proteus mirabilis
isolates were recovered from intensive care units in the Second Affiliated Hospital of Zhejiang University during a 3-month period. The isolates showed a high level of resistance against ciprofloxacin, in addition to their resistance against the carbapenems. Pulsed-field gel electrophoresis (PFGE) analysis showed that these isolates belonged to three clonal strains. PCRs and DNA sequence analysis of the carbapenemase and other β-lactamase genes indicated that all the isolates harbored the
bla
KPC-2
gene. Twelve of 19 isolates harbored the plasmid-mediated quinolone resistance (PMQR) genes, both the
qnrD
and
aac(6
′
)-Ib-cr
genes. Eight representative isolates with high levels of quinolone resistance carried the similar mutation profiles of S83I in
gyrA
, E466D in
gyrB
, and S80I in
parC
. Reduced carbapenem susceptibility was transferred to
Escherichia coli
(EC600) in a conjugation experiment, while the quinolone resistance was not. DNA hybridization showed that
qnrD
was located on a plasmid of approximately 4.5 kb. In summary, large clonally related isolates of KPC-2-producing
P. mirabilis
emerged in a Chinese hospital, and
qnrD
was detected in KPC-producing
P. mirabilis
for the first time.
Peroral Ciprofloxacin Therapy Impairs the Generation of a Protective Immune Response in a Mouse Model for Salmonella enterica Serovar Typhimurium Diarrhea, while Parenteral Ceftriaxone Therapy Does Not
Authors: Endt Kathrin , Maier Lisa , Käppeli Rina , Barthel Manja , Misselwitz Benjamin , Kremer Marcus , Hardt Wolf-Dietrich 
Published: February 2012

ABSTRACT

Nontyphoidal
Salmonella
(NTS) species cause self-limiting diarrhea and sometimes severe disease. Antibiotic treatment is considered only in severe cases and immune-compromised patients. The beneficial effects of antibiotic therapy and the consequences for adaptive immune responses are not well understood. We used a mouse model for
Salmonella
diarrhea to assess the effects of
per os
treatment with ciprofloxacin (15 mg/kg of body weight intragastrically 2 times/day, 5 days) or parenteral ceftriaxone (50 mg/kg intraperitoneally, 5 days), two common drugs used in human patients. The therapeutic and adverse effects were assessed with respect to generation of a protective adaptive immune response, fecal pathogen excretion, and the emergence of nonsymptomatic excreters. In the mouse model, both therapies reduced disease severity and reduced the level of fecal shedding. In line with clinical data, in most animals, a rebound of pathogen gut colonization/fecal shedding was observed 2 to 12 days after the end of the treatment. Yet, levels of pathogen shedding and frequency of appearance of nonsymptomatic excreters did not differ from those for untreated controls. Moreover, mice treated intraperitoneally with ceftriaxone developed an adaptive immunity protecting the mice from enteropathy in wild-type
Salmonella enterica
serovar Typhimurium challenge infections. In contrast, the mice treated intragastrically with ciprofloxacin were not protected. Thus, antibiotic treatment regimens can disrupt the adaptive immune response, but treatment regimens may be optimized in order to preserve the generation of protective immunity. It might be of interest to determine whether this also pertains to human patients. In this case, the mouse model might be a tool for further mechanistic studies.
Targeted Intracellular Delivery of Antituberculosis Drugs to Mycobacterium tuberculosis-Infected Macrophages via Functionalized Mesoporous Silica Nanoparticles
Authors: Clemens Daniel L. , Lee Bai-Yu , Xue Min , Thomas Courtney R. , Meng Huan , Ferris Daniel , Nel Andre E. , Zink Jeffrey I. , Horwitz Marcus A. 
Published: February 2012

ABSTRACT

Delivery of antituberculosis drugs by nanoparticles offers potential advantages over free drug, including the potential to target specifically the tissues and cells that are infected by
Mycobacterium tuberculosis
, thereby simultaneously increasing therapeutic efficacy and decreasing systemic toxicity, and the capacity for prolonged release of drug, thereby allowing less-frequent dosing. We have employed mesoporous silica nanoparticle (MSNP) drug delivery systems either equipped with a polyethyleneimine (PEI) coating to release rifampin or equipped with cyclodextrin-based pH-operated valves that open only at acidic pH to release isoniazid (INH) into
M. tuberculosis
-infected macrophages. The MSNP are internalized efficiently by human macrophages, traffic to acidified endosomes, and release high concentrations of antituberculosis drugs intracellularly. PEI-coated MSNP show much greater loading of rifampin than uncoated MSNP and much greater efficacy against
M. tuberculosis-
infected macrophages. MSNP were devoid of cytotoxicity at the particle doses employed for drug delivery. Similarly, we have demonstrated that the isoniazid delivered by MSNP equipped with pH-operated nanovalves kill
M. tuberculosis
within macrophages significantly more effectively than an equivalent amount of free drug. These data demonstrate that MSNP provide a versatile platform that can be functionalized to optimize the loading and intracellular release of specific drugs for the treatment of tuberculosis.
Altered Murine Tissue Colonization by Borrelia burgdorferi following Targeted Deletion of Linear Plasmid 17-Carried Genes
Authors: Casselli Timothy , Tourand Yvonne , Bankhead Troy 
Published: February 2012

ABSTRACT

The causative agent of Lyme disease,
Borrelia burgdorferi
, possesses a segmented genome comprised of a single linear chromosome and upwards of 23 linear and circular plasmids. Much of what is known about plasmid-borne genes comes from studying laboratory clones that have spontaneously lost one or more plasmids during
in vitro
passage. Some plasmids, including the linear plasmid lp17, are never or rarely reported to be lost during routine culture; therefore, little is known about the requirement of these conserved plasmids for infectivity. In this study, the effects of deleting regions of lp17 were examined both
in vitro
and
in vivo
. A mutant strain lacking the genes
bbd16
to
bbd25
showed no deficiency in the ability to establish infection or disseminate to the bloodstream of mice; however, colonization of peripheral tissues was delayed. Despite the ability to colonize ear, heart, and joint tissues, this mutant exhibited a defect in bladder tissue colonization for up to 56 days postinfection. This phenotype was not observed in immunodeficient mice, suggesting that bladder colonization by the mutant strain was inhibited by an adaptive immune-based mechanism. Moreover, the mutant displayed increased expression of outer surface protein C
in vitro
, which was correlated with the absence of the gene
bbd18
. To our knowledge, this is the first report involving genetic manipulation of lp17 in an infectious clone of
B. burgdorferi
and reveals for the first time the effects of lp17 gene deletion during murine infection by the Lyme disease spirochete.
GLADE
Authors: Rusu Florin , Dobra Alin 
Published: February 2012

In this paper we introduce GLADE, a scalable distributed framework for large scale data analytics. GLADE consists of a simple user-interface to define Generalized Linear Aggregates (GLA), the fundamental abstraction at the core of GLADE, and a distributed runtime environment that executes GLAs by using parallelism extensively.
GLAs are derived from User-Defined Aggregates (UDA), a relational database extension that allows the user to add specialized aggregates to be executed inside the query processor. GLAs extend the UDA interface with methods to Serialize/Deserialize the state of the aggregate required for distributed computation. As a significant departure from UDAs which can be invoked only through SQL, GLAs give the user direct access to the state of the aggregate, thus allowing for the computation of significantly more complex aggregate functions.
GLADE runtime is an execution engine optimized for the GLA computation. The runtime takes the user-defined GLA code, compiles it inside the engine, and executes it right near the data by taking advantage of parallelism both inside a single machine as well as across a cluster of computers. This results in maximum possible execution time performance (all our experimental tasks are I/O-bound) and linear scaleup.