bluuebunny/crossref_metadata_2025 huggingface dataset:
Epitope Mapping of the Hemagglutinin Molecule of A/(H1N1)pdm09 Influenza Virus by Using Monoclonal Antibody Escape Mutants
Authors: Matsuzaki Yoko , Sugawara Kanetsu , Nakauchi Mina , Takahashi Yoshimasa , Onodera Taishi , Tsunetsugu-Yokota Yasuko , Matsumura Takayuki , Ato Manabu , Kobayashi Kazuo , Shimotai Yoshitaka , Mizuta Katsumi , Hongo Seiji , Tashiro Masato , Nobusawa Eri
Published: August 2014

We determined the antigenic structure of pandemic influenza A(H1N1)pdm09 virus hemagglutinin (HA) using 599 escape mutants that were selected using 16 anti-HA monoclonal antibodies (MAbs) against A/Narita/1/2009. The sequencing of mutant HA genes revealed 43 amino acid substitutions at 24 positions in three antigenic sites, Sa, Sb, and Ca2, which were previously mapped onto A/Puerto Rico/8/34 (A/PR/8/34) HA (A. J. Caton, G. G. Brownlee, J. W. Yewdell, and W. Gerhard, Cell 31:417–427, 1982), and an undesignated site, i.e., amino acid residues 141, 142, 143, 171, 172, 174, 177, and 180 in the Sa site, residues 170, 173, 202, 206, 210, 211, and 212 in the Sb site, residues 151, 154, 156, 157, 158, 159, 200, and 238 in the Ca2 site, and residue 147 in the undesignated site (numbering begins at the first methionine). Sixteen MAbs were classified into four groups based on their cross-reactivity with the panel of escape mutants in the hemagglutination inhibition test. Among them, six MAbs targeting the Sa and Sb sites recognized both residues at positions 172 and 173. MAb n2 lost reactivity when mutations were introduced at positions 147, 159 (site Ca2), 170 (site Sb), and 172 (site Sa). We designated the site consisting of these residues as site Pa. From 2009 to 2013, no antigenic drift was detected for the A(H1N1)pdm09 viruses. However, if a novel variant carrying a mutation at a position involved in the epitopes of several MAbs, such as 172, appeared, such a virus would have the advantage of becoming a drift strain.

IMPORTANCE
The first influenza pandemic of the 21st century occurred in 2009 with the emergence of a novel virus originating with swine influenza, A(H1N1)pdm09. Although HA of A(H1N1)pdm09 has a common origin (1918 H1N1) with seasonal H1N1, the antigenic divergence of HA between the seasonal H1N1 and A(H1N1)pdm09 viruses gave rise to the influenza pandemic in 2009. To take precautions against the antigenic drift of the A(H1N1)pdm09 virus in the near future, it is important to identify its precise antigenic structure. To obtain various mutants that are not neutralized by MAbs, it is important to neutralize several plaque-cloned parent viruses rather than only a single parent virus. We characterized 599 escape mutants that were obtained by neutralizing four parent viruses of A(H1N1)pdm09 in the presence of 16 MAbs. Consequently, we were able to determine the details of the antigenic structure of HA, including a novel epitope.
DESC1 and MSPL Activate Influenza A Viruses and Emerging Coronaviruses for Host Cell Entry
Authors: Zmora Pawel , Blazejewska Paulina , Moldenhauer Anna-Sophie , Welsch Kathrin , Nehlmeier Inga , Wu Qingyu , Schneider Heike , Pöhlmann Stefan , Bertram Stephanie
Published: August 2014

The type II transmembrane serine protease (TTSP) TMPRSS2 cleaves and activates the influenza virus and coronavirus surface proteins. Expression of TMPRSS2 is essential for the spread and pathogenesis of H1N1 influenza viruses in mice. In contrast, H3N2 viruses are less dependent on TMPRSS2 for viral amplification, suggesting that these viruses might employ other TTSPs for their activation. Here, we analyzed TTSPs, reported to be expressed in the respiratory system, for the ability to activate influenza viruses and coronaviruses. We found that MSPL and, to a lesser degree, DESC1 are expressed in human lung tissue and cleave and activate the spike proteins of the Middle East respiratory syndrome and severe acute respiratory syndrome coronaviruses for cell-cell and virus-cell fusion. In addition, we show that these proteases support the spread of all influenza virus subtypes previously pandemic in humans. In sum, we identified two host cell proteases that could promote the amplification of influenza viruses and emerging coronaviruses in humans and might constitute targets for antiviral intervention.

IMPORTANCE
Activation of influenza viruses by host cell proteases is essential for viral infectivity and the enzymes responsible are potential targets for antiviral intervention. The present study demonstrates that two cellular serine proteases, DESC1 and MSPL, activate influenza viruses and emerging coronaviruses in cell culture and, because of their expression in human lung tissue, might promote viral spread in the infected host. Antiviral strategies aiming to prevent viral activation might thus need to encompass inhibitors targeting MSPL and DESC1.
Emergence of Broadly Neutralizing Antibodies and Viral Coevolution in Two Subjects during the Early Stages of Infection with Human Immunodeficiency Virus Type 1
Authors: Sather D. Noah , Carbonetti Sara , Malherbe Delphine C. , Pissani Franco , Stuart Andrew B. , Hessell Ann J. , Gray Mathew D. , Mikell Iliyana , Kalams Spyros A. , Haigwood Nancy L. , Stamatatos Leonidas
Published: August 2014

Delineating the key early events that lead to the development of broadly neutralizing anti-HIV-1 antibodies during natural infection may help guide the development of immunogens and vaccine regimens to prevent HIV-1 infection. In this study, we monitored two HIV-1-positive subjects, VC20013 and VC10014, over the course of infection from before they developed broadly neutralizing antibody (bNAb) activity until several years after neutralizing breadth was detected in plasma. Both subjects developed bNAb activity after approximately 1 year postinfection, which ultimately mapped to the membrane-proximal external region (MPER) in VC20013 and an epitope that overlaps the CD4 receptor binding site in VC10014. In subject VC20013, we were able to identify anti-MPER activity in the earliest plasma sample that exhibited no bNAb activity, indicating that this epitope specificity was acquired very early on, but that it was initially not able to mediate neutralization. Escape mutations within the bNAb epitopes did not arise in the circulating envelopes until bNAb activity was detectable in plasma, indicating that this early response was not sufficient to drive viral escape. As bNAb activity began to emerge in both subjects, we observed a simultaneous increase in autologous antienvelope antibody binding affinity, indicating that antibody maturation was occurring as breadth was developing. Our findings illustrate one potential mechanism by which bNAbs develop during natural infection in which an epitope target is acquired very early on during the course of infection but require time and maturation to develop into broadly neutralizing activity.

IMPORTANCE
One major goal of HIV-1 vaccine research is the development of a vaccine that can elicit broadly neutralizing antibodies (bNAbs). Although no such vaccine exists, bNAbs develop in approximately 20% of HIV-1-infected subjects, providing a prototype of the bNAbs that must be reelicited by vaccine. Thus, there is significant interest in understanding the mechanisms by which bNAbs develop during the course of infection. We studied the timing, epitope specificity, and evolution of the bNAb responses in two HIV-1-positive patients who developed bNAb activity within the first several years after infection. In one subject, antibodies to a broadly neutralizing epitope developed very early but were nonneutralizing. After several months, neutralizing activity developed, and the virus mutated to escape their activity. Our study highlights one mechanism for the development of bNAbs where early epitope acquisition followed by sufficient time for antibody maturation drives the epitope-specific antibody response toward broadly neutralizing activity.
Septic sacroiliitis revealing an infectious endocarditis
Authors: Mahfoudhi Madiha , Hariz Anis , Turki Sami , Kheder Adel
Published: August 2014

We report the case of a 43-year-old man admitted for right hip ache and fever. Physical examination revealed a fever, an ache at the manipulation of the sacroiliac joint and a limitation of abduction and external rotation of the right hip. There was no murmur in cardiac auscultation. No anomaly was found at the conventional radiographs of the sacroiliac joint, while the pelvic MRI confirmed a right sacroiliitis. A sacroiliac puncture with a study of synovial fluid demonstrated the presence ofStreptococcus viridans. The blood culture revealed the same germ. Transthoracic and transoesophageal echocardiography confirmed infectious endocarditis with vegetation in the mitral valve. He received penicillin G and gentamicin relayed by pristinamycin because of an allergy to penicillin G with a total duration of treatment of 40 days. His symptoms and the laboratory and radiological tests abnormalities resolved totally with no recurrence.
West-African trypanosomiasis in a returned traveller from Ghana: an unusual cause of progressive neurological decline
Authors: Elliott Ivo , Patel Trupti , Shah Jagrit , Venkatesan Pradhib
Published: August 2014

West-African trypanosomiasis caused byTrypanosoma brucei gambienseis a rare imported infection presenting with somnolence, lymphadenopathy and wide-ranging neurological symptoms. A 67-year-old Caucasian man presented with a 10-month history of cognitive deterioration, ataxic gait, somnolence and urinary incontinence. His symptoms had progressed more rapidly over the course of a month prior to admission. Serological testing confirmed a diagnosis of West-African trypanosomiasis. The patient was successfully treated with eflornithine and made a good recovery. West-African trypanosomiasis should be considered in the differential diagnosis of unexplained cognitive decline in those with a relevant travel history. If left untreated, the condition is universally fatal.
Elevated 1 h postload plasma glucose levels identify adults with normal glucose tolerance but increased risk of non-alcoholic fatty liver disease
Authors: Sesti Giorgio , Hribal Marta Letizia , Fiorentino Teresa Vanessa , Sciacqua Angela , Perticone Francesco
Published: August 2014

Objective

To determine the ability of the proposed diagnostic value of a 1-h OGTT glucose ≥155mg/dL to identify individuals with non-alcoholic fatty liver disease (NAFLD) diagnosed by ultrasonography in a cohort of adult white individuals.

Design

The study group comprised 710 white individuals participating to the CATAnzaro MEtabolic RIsk factors (CATAMERI) Study, a cross-sectional study assessing cardio-metabolic risk factors in individuals carrying at least one risk factor including dysglycemia, overweight/obesity, hypertension, dyslipidemia. a 75 g oral Oral Glucose Tolerance Test (OGTT) was performed with 0, 30, 60, 90 and 120 min sampling for plasma glucose and insulin measurements. Cardio-metabolic risk factors including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were assessed in the whole cohort.

Results

Of the 710 participants examined, 295 had normal glucose tolerance (NGT) with 1-hour post-load plasma glucose <155 mg/dL (NGT 1h-low), 109 individuals had NGT 1h-high, 104 had isolated impaired fasting glucose (IFG), and 202 had impaired glucose tolerance (IGT). As compared with NGT 1h-low, NGT 1h-high and IGT subjects exhibited significantly higher body mass index (BMI), triglycerides, high sensitivity C reactive protein, ALT, GGT, and hepatic insulin resistance (IR), assessed by the liver IR index, as well as lower high density lipoprotein, and insulin-like growth factor-1 (IGF-1) levels. In a logistic regression analysis adjusted for age, gender, and BMI, NGT 1h-high participants had a 1.5-fold increased risk of having NAFLD and an even increased risk was observed in subjects with IGT (1.8-fold), but not in the isolated IFG group (1.01-fold).

Conclusions

These data suggest that the value of a 1-hour OGTT glucose ≥155 mg/dL may be helpful to identify a subset of NGT individuals at risk for NAFLD.
Current and future use of point-of-care tests in primary care: an international survey in Australia, Belgium, The Netherlands, the UK and the USA
Authors: Howick Jeremy , Cals Jochen W L , Jones Caroline , Price Christopher P , Plüddemann Annette , Heneghan Carl , Berger Marjolein Y , Buntinx Frank , Hickner John , Pace Wilson , Badrick Tony , Van den Bruel Ann , Laurence Caroline , van Weert Henk C , van Severen Evie , Parrella Adriana , Thompson Matthew
Published: August 2014

Objective

Despite the growing number of point-of-care (POC) tests available, little research has assessed primary care clinician need for such tests. We therefore aimed to determine which POC tests they actually use or would like to use (if not currently available in their practice).

Design

Cross-sectional survey.

Setting

Primary care in Australia, Belgium (Flanders region only), the Netherlands, the UK and the USA.

Participants

Primary care doctors (general practitioners, family physicians).

Main measures

We asked respondents to (1) identify conditions for which a POC test could help inform diagnosis, (2) from a list of tests provided: evaluate which POC tests they currently use (and how frequently) and (3) determine which tests (from that same list) they would like to use in the future (and how frequently).

Results

2770 primary care clinicians across five countries responded. Respondents in all countries wanted POC tests to help them diagnose acute conditions (infections, acute cardiac disease, pulmonary embolism/deep vein thrombosis), and some chronic conditions (diabetes, anaemia). Based on the list of POC tests provided, the most common tests currently used were: urine pregnancy, urine leucocytes or nitrite and blood glucose. The most commonly reported tests respondents expressed a wish to use in the future were: D-dimer, troponin and chlamydia. The UK and the USA reported a higher actual and desired use for POC tests than Australia, Belgium and the Netherlands. Our limited data suggest (but do not confirm) representativeness.

Conclusions

Primary care clinicians in all five countries expressed a desire for POC tests to help them diagnose a range of acute and chronic conditions. Rates of current reported use and desired future use were generally high for a small selection of POC tests, but varied across countries. Future research is warranted to explore how specific POC tests might improve primary care.
THE AHEAD STUDY: MANAGING ANTICOAGULATED PATIENTS WHO SUFFER HEAD INJURY
Authors: Mason Suzanne , Kuczawski Maxine , Teare Marion D , Stevenson Matthew , Holmes Michael , Ramlakhan Shammi , Goodacre Steve , Morris Francis , Harper Rosemary
Published: August 2014

Objectives & Background

Existing practice in emergency departments (ED) in the UK for managing anticoagulated patients after blunt head trauma is variable and based on limited evidence. We aimed to determine the head injury complication rate within this group of patients and identify risk factors associated with a poor outcome.

Methods

A prospective observational multi-centre study enrolled patients taking warfarin who attended 33 emergency departments in England and Scotland after blunt head trauma. ED attendance data and patient reported outcomes were collected over an 18-month period from October 2011. Head injury complication was defined by head injury-related death, neurosurgery resulting from injury, clinically-significant CT head scan or re-attendance with significant head injury complications. Factors including neurological status (Glasgow Coma Score, GCS), level of anticoagulation (INR) and neurological symptoms were entered into multivariate logistic regression analyses as predictors of a poor outcome.

Results

A total of 3566 patients were enrolled; anonymised clinical data was submitted for 99.1% of patients. The age range was 18 to 101 years (median 81 yrs, IQR 12), 48.7% were men. Mean initial INR was 2.67 (SD 1.34, IQR 1.1), 80.5% patients had a GCS of 15 and 68.1% did not report any associated neurological symptoms. 59.3% of patients had a CT head scan with a significant head injury-related finding identified in 5.6%. Reversal therapy was given to 5.3% of patients, only 19 (0.5%) patients underwent neurosurgery and 42 (1.2%) patients died of a head injury-related death. The overall rate of head injury complication was found to be 6.1%. Multivariate logistic regression modelling found GCS <13 (OR 12.7; 95% CI 2.41 to 67.2), vomiting (OR 3.09; 95% CI 1.71 to 5.61) and loss of consciousness (OR 2.53; 95% CI 1.54 to 4.15) to be significantly associated with a poor outcome. In univariate analyses an INR >4 was associated with an increased risk of an adverse outcome, however it made no significant contribution to the multivariable models.

Conclusion

This is the largest cohort of anticoagulated head injury patients ever reported. The head injury complication rate was 6.1% which correlates well with previous findings. INR was not found to be associated with a poor outcome however GCS <13, vomiting and loss of consciousness were identified as significant risk factors for an adverse outcome in anticoagulated patients with a head injury.
ORAL PREDNISOLONE IN THE TREATMENT OF ACUTE GOUT: A PRAGMATIC, MULTI-CENTRE, DOUBLE-BLIND, RANDOMIZED, EQUIVALENCE TRIAL
Authors: Rainer Timothy H , Cheng Chi H , Graham Colin A , Janssens Hein J , Man Chi Y , Tam Lai S , Choi Yu F , Yau Wah H , Lee Ka H
Published: August 2014

Objectives & Background

To compare oral prednisolone with oral indomethacin in patients presenting to emergency departments (ED) with acute gout firstly for analgesic effectiveness, and secondly for safety.

Methods

Pragmatic, multi-centre, double-blind, randomized, equivalence trial. Each patient received either oral indomethacin plus placebo or prednisolone plus placebo for 5 days. Data were analysed in the first two hours in the ED, and from days 1 to 14.

Results

416 patients were recruited (208 patients in each arm), and 376 patients completed the study. Clinically significant reductions in mean pain score were observed within two hours of treatment with both indomethacin and prednisolone both at rest and with activity, and also over the subsequent 14 days. The margin of equivalence seta prioriat 13% between the two arms was not breached. There were no major adverse events during the ED or later phases of the study. In the first two hours, there were minor adverse events affecting 34 (18%) patients in the indomethacin group and 10 (5.3%) patients in the prednisolone group (P<0.001). From day 1 to day 14, 75 (39%) patients in the indomethacin group and 75 (40%) patients in the prednisolone group suffered from mild side effects (P=0.50).

Conclusion

Prednisolone and Indomethacin are equally effective first line treatments for acute gout in ED patients. There were no serious adverse event rates during a follow-up period of 14 days.
THE DIAGNOSTIC UTILITY OF D-DIMER, AND OTHER CLINICAL VARIABLES IN PREGNANT AND POSTPARTUM PATIENTS WITH SUSPECTED ACUTE PULMONARY EMBOLISM
Authors: Choi Hyun , Krishnamoorthy Dinesh
Published: August 2014

Objectives & Background

Pulmonary Embolism (PE) in pregnancy remains one of the leading causes of maternal morbidity and mortality in the developed world. However, there is a paucity of high quality evidence resulting in a lack of consensus in managing this group of patients. The aim of the study was to address the diagnostic utility of D dimer for suspected PE in pregnant and postpartum patients, and to identify any clinical presentation variables that are predictors of PE in this group of patients.

Methods

A retrospective case note review of 152 pregnant and postpartum patients who underwent diagnostic imaging (Ventilation/Perfusion (V/Q) or computed tomographic pulmonary angiography (CTPA)) for suspected PE at a tertiary teaching hospital from 2007 to 2011 was conducted. The reference range for D-dimer was less than 0.5 mg/L as being normal. The following variables were also assessed in terms of their predictive capability for PE diagnosis in pregnancy; Heart Rate (HR), Mean Arterial Pressure (MAP), Shock Index (SI), and A-a gradient.

Results

The application of D-dimer testing for suspected PE in this study population had a sensitivity of 100% (95% CI, 73%– 100%), specificity of 42% (95% CI, 31%–53%), and a likelihood negative ratio of 0. None of the clinical variables were significant predictors of PE according to regression analyses: d-dimer odds ratio (OR) 1.52 95% CI [0.95, 2.42], HR OR 1.02 95% CI [0.56, 1.85], MAP OR 1.54 95% CI [0.89, 2.66], SI OR 0.70 95% CI [0.33, 1.51] and A-a gradient OR 2.08 95% CI [0.93, 4.62].

Conclusion

According to our study, there is supportive evidence that a negative D-dimer result is useful as a means of ruling out PE in pregnant and post-partum patients. However, we need a larger prospective observational study to collaborate the findings.
EMERGENCIES BY APPOINTMENT: WOULD PATIENTS WITH MINOR INJURIES PREFER A BOOKED APPOINTMENT AT THEIR LOCAL EMERGENCY DEPARTMENT TO THE CURRENT WALK-IN SERVICE PROVISION
Authors: Roberts Lynn , Dykes Linda
Published: August 2014

Objectives & Background

Emergency Departments (ED) typically offer walk-in services for minor injuries, and patients arriving at peak times may experience delays. Other NHS services (e.g. GP, dentists and GUM) utilise booked appointments even for urgent problems.

We wished to ascertain whether patients attending our ED (a DGH with a very large rural catchment area) with minor injuries would find an appointment system accessed via phone/internet acceptable, and also their views on perhaps being asked to return for an appointment later the same (or following) day, should they arrive when waiting times are unacceptably long.

Methods

A cross-sectional sample of 512 ED attendees with minor injuries/conditions were identified by the triage nurse. A questionnaire with a semi-structured design was used to determine the experiences, opinions and preferences of patients with minor injuries/conditions in relation to the proposed development of an appointment system. Ethical approval was obtained. Statistical analysis used mainly non-parametric tests plus descriptive statistics, with cluster analysis used to predict associations with patients' willingness to accept booked appointment.

Results

Overall, most participants (79%) indicated they were strongly supportive of the concept of booked appointments as an alternative to the current “walk-in” system, particularly those who would book by internet/phone (p=0.000).

Younger patients, those in employment, and those with lower levels of anxiety and perceived urgency were also significantly more likely to find booked appointments acceptable.

Being asked to return for a later appointment having already arrived at the ED was deemed less popular, although patients living closer to the hospital were more likely to find being asked to return for an appointment acceptable (p=0.012).

Conclusion

This study confirms acceptance of the concept of ED offering appointments to minor injury patients. Participants would prefer pre-booked appointments over being asked to return later or next day, but they would accept either in preference to enduring excessive delays.
PRE-HOSPITAL NON-INVASIVE VENTILATION FOR ACUTE RESPIRATORY FAILURE: A SYSTEMATIC REVIEW AND NETWORK META ANALYSIS
Authors: Goodacre Steve
Published: August 2014

Objectives & Background

We aimed to determine the effectiveness of pre-hospital continuous positive airway pressure (CPAP) or bi-level inspiratory positive airway pressure (BiPAP) compared with usual care for adults presenting to the emergency services with acute respiratory failure.

Methods

We searched 14 electronic databases and research registers from inception to August 2013. Searches were supplemented by hand-searching the reference list of relevant articles (including citation searching), the World Wide Web and contacting experts in the field. We selected randomised or quasi-randomised controlled trials that compared pre-hospital NIV to a relevant comparator treatment in patients with acute respiratory failure. An aggregate data network meta-analysis was used to jointly estimate intervention effects relative to standard care. A network meta-analysis using a mixture of individual patient-level data (IPD) and aggregate data was carried out to assess potential treatment effect modifiers.

Results

The literature searches identified 2284 citations. Eight randomised and two quasi-randomised controlled trials (six CPAP; four BiPAP; sample sizes 23 to 207) were selected for inclusion. The aggregate data network meta-analysis suggested that CPAP was the most effective treatment in terms of mortality (probability=0.989) and intubation rate (probability=0.639), and reduced both mortality (odds ratio 0.41; 95% CrI (credible interval) 0.20 to 0.77) and intubation rate (0.32; 95% CrI 0.17 to 0.62) compared to standard care. The effect of BiPAP upon mortality (odds ratio 1.94; 95% CrI 0.65 to 6.14) and intubation rate (odds ratio 0.40; 95% CrI 0.14 to 1.16) was uncertain. The network meta-analysis using IPD and aggregate data suggested that sex was a modifier of the effect of treatment on mortality.

Conclusion

Pre-hospital CPAP can reduce mortality and intubation rates compared to standard care, while the effectiveness of pre-hospital BiPAP is uncertain.

Comparison of mortality for interventions versus standard care from the primary trials
Statin therapy in patients with cirrhosis
Authors: Wright Andrew P , Adusumalli Srinath , Corey Kathleen E
Published: August 2014

Cardiovascular disease is one of the leading causes of death among patients with cirrhosis and following liver transplantation. Although 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (‘statins’) reduce the risk of cardiovascular events, fears about hepatotoxicity have historically led to underuse in patients with liver disease. In addition, the pharmacokinetics of statins can be significantly altered in cirrhosis, creating challenges with their use in liver disease. However, emerging data from randomised controlled trials and observational studies suggest that statin therapy appears to be safe and effective in patients with chronic liver disease and compensated cirrhosis. The cardiovascular risk benefits as well as the potential pleiotropic benefits of statins warrants strong consideration of use of statin therapy in patients with cirrhosis.
Functional, morphological and electrocardiographical abnormalities in patients with apical hypertrophic cardiomyopathy and apical aneurysm: correlation with cardiac MR
Authors: Suwa Kenichiro , Satoh Hiroshi , Sano Makoto , Nobuhara Mamoru , Saitoh Takeji , Saotome Masao , Urushida Tsuyoshi , Katoh Hideki , Tawarahara Kei , Ohtani Hayato , Wakabayashi Yasushi , Takase Hiroyuki , Terada Hajime , Takehara Yasuo , Sakahara Harumi , Hayashi Hideharu
Published: August 2014

Objective

The prognosis of apical hypertrophic cardiomyopathy (APH) has been benign, but apical myocardial injury has prognostic importance. We studied functional, morphological and electrocardiographical abnormalities in patients with APH and with apical aneurysm and sought to find parameters that relate to apical myocardial injury.

Methods

Study design: a multicentre trans-sectional study.Patients: 45 patients with APH and 5 with apical aneurysm diagnosed with transthoracic echocardiography (TTE) in the database of Hamamatsu Circulation Forum.Measure: the apical contraction with cine-cardiac MR (CMR), the myocardial fibrotic scar with late gadolinium enhancement (LGE)-CMR, and QRS fragmentation (fQRS) defined when two ECG-leads exhibited RSR’s patterns.

Results

Cine-CMR revealed 27 patients with normal, 12 with hypokinetic and 11 with dyskinetic apical contraction. TTE misdiagnosed 11 (48%) patients with hypokinetic and dyskinetic contraction as those with normal contraction. Apical LGE was apparent in 10 (83%) and 11 (100%) patients with hypokinetic and dyskinetic contraction, whereas only in 11 patients (41%) with normal contraction (p<0.01). Patients with dyskinetic apical contraction had the lowest left ventricular ejection fraction, the highest prevalence of ventricular tachycardia, and the smallest ST depression and depth of negative T waves. The presence of fQRS was associated with impaired apical contraction and apical LGE (OR=8.32 and 8.61, p<0.05).

Conclusions

CMR is superior to TTE for analysing abnormalities of the apex in patients with APH and with apical aneurysm. The presence of fQRS can be a promising parameter for the early detection of apical myocardial injury.
Molecular cytogenetics and phylogenetic analysis of Brazilian leaf frog species of the genera Phyllomedusa and Phasmahyla (Hylidae: Phyllomedusinae)
Authors: Barth Adriane , Vences Miguel , Solé Mirco , Costa Marco Antonio
Published: August 2014

In this study we describe the karyotypes and molecular phylogenetic relationships of the leaf frogs Phyllomedusa bahiana Lutz, 1925, Phyllomedusa burmeisteri Boulenger, 1882, Phyllomedusa nordestina Caramaschi, 2006, Phyllomedusa rohdei Mertens, 1926, Phyllomedusa hypochondrialis (Daudin, 1800), and Phasmahyla spectabilis Cruz, Feio and Nascimento, 2008. We analyzed the karyotypes using C-banding, fluorochrome staining, and fluorescence in situ hybridization of telomeric probe, and inferred phylogeny using nuclear tyrosinase and mitochondrial 16S rDNA sequences. Heterochromatin distribution in P. nordestina diverged from the other species, and P. bahiana and P. rohdei showed evident interstitial telomere sequences. Molecular analyzes confirmed the current taxonomic classification, grouping mitochondrial DNA sequences of each species, and usually without haplotype sharing in the nuclear gene. We also extended the distribution of P. burmeisteri to northern Bahia state and restricted P. bahiana to southern Bahia state, with a discrete extension of the range of P. bahiana to the north and northeast of Minas Gerais state. The tyrosinase haplotype network showed a haplotype shared between P. bahiana and P. burmeisteri from Porto Seguro, Bahia. Based on this, we suggest a new distribution in the overlapping area between these two species, which according to our data ranges between Porto Seguro and Camacan, in Bahia state.
Characterization of gross composition, energy value, and fatty acid profile of milk from lowland tapir (Tapirusterrestris) during different lactation periods
Authors: Van Nieuwenhove C. , Pérez M.E. , Hernández M. , Luna Pizarro P.
Published: August 2014

We evaluated gross composition, energy value, and fatty acid profile of colostrum, transitional, and mature milk of lowland tapir (Tapirus terrestris (L., 1758)) from Argentina. Samples were obtained from six healthy animals kept in captive or semicaptive conditions. Protein content varied over time from 6 to 19 g/100 g of milk; carbohydrates varied from 2.4 to 5.4 g/100 g of milk; fat varied from 2.4 to 17.3 g/100 g of milk. Energy value also varied over time, with colostrum having the highest value. Fatty acid profile revealed a unique pattern in tapir milk, characterized by the presence of higher amounts of lauric, myristic, and pentadecanoic acids than in milk from other equids. Traces of conjugated linoleic acid (CLA) were measured, being the only trans fatty acid detected in tapir milk. Neither butyric acid (C4:0) nor fatty acids longer than C18 were found in tapir milk. The characteristics of tapir milk include high concentration of fat, caseins, and whey proteins. Gross composition and saturated fatty acid to unsaturated fatty acid (SFA/UFA) ratio of tapir milk were more similar to that of horse milk than rhinoceros milk. The present study sheds light on tapir fatty acid metabolism and on nutritional requirements of their newborns, which can be used to improve conservation and management strategies. Furthermore, different periods of lactation were evaluated in this species for the first time, thus contributing to the general knowledge of milk from other members of the order Perissodactyla.
A tale of lost tails: pseudoautotomy in the Neotropical snake genusDrymoluber(Serpentes: Colubridae)
Authors: Costa H.C. , Moura M.R. , Feio R.N.
Published: August 2014

Pseudoautotomy (no spontaneous tail breakage without regeneration) occurs in the snakes Drymoluber brazili (Gomes, 1918) and Drymoluber dichrous (Peters, 1863) throughout their geographic range. Examination of 197 specimens of D. dichrous and 60 D. brazili show, respectively, a frequency of tail breakage (FTB) in 26% and 40% of specimens, similar or higher than observed for most species with pseudoautotomy. There is no sexual difference in FTB for D. brazili, and no relationship between tail breakage and snout–vent length (SVL). For D. dicrous, tail breakage is more frequently observed in males when specimens are <710 mm SVL, but for longer specimens, the FTB is higher in females; this strange pattern may not be explained by a single hypothesis. The FTB does not vary significantly between disjunct populations of D. dichrous, suggesting that they are subject to similar predation pressures and escape rates, or minor or no effect of habitat structure on predation risk. The FTB increases with SVL in D. dichrous (but not in D. brazili, probably due to sample size), which is an indication that as the snake grows, the chance of being injured increases and partial tail loss becomes an efficient defense. The multiple tail break hypothesis is not supported for the genus Drymoluber Amaral, 1930, remaining restricted to taxa with specialized pseudoautotomy.
Minimization of energy per particle among Bravais lattices in ℝ2: Lennard–Jones and Thomas–Fermi cases
Authors: Bétermin Laurent , Zhang Peng
Published: August 2014

We prove in this paper that the minimizer of Lennard–Jones energy per particle among Bravais lattices is a triangular lattice, i.e. composed of equilateral triangles, in ℝ2 for large density of points, while it is false for sufficiently small density. We show some characterization results for the global minimizer of this energy and finally we also prove that the minimizer of the Thomas–Fermi energy per particle in ℝ2 among Bravais lattices with fixed density is triangular.
Design and modeling of microneedle integrated with microactuator for drug delivery
Authors: Girija Sravani K. , Srinivas Y. , Swain Bikash , Sunil Banu K. , Srinivasa Rao K.
Published: August 2014

Today's world has very much demand for the development of microscale devices, due to its less cost, space requirements, high-dimensional stability and especially manufacturing time. In this paper, we have design and simulated MEMS based microactuator and microneedle integration which will be very helpful for blood sampling device like e-mosquito. The dimensions of the modeled beam are of 100 mm long, 30 mm width, 10 mm thickness. This new design model consists of piezoceramic material sandwiched between two metal electrodes and the piezoelectric actuator is made with microneedle which will help for blood sampling purposes. The results after the simulation of this new model present that it will be suitable for blood sampling analysis with aluminum as electrodes and silicon as microneedle.
OPTICAL GAIN AND ENERGY BAND STRUCTURE OF PHOTONIC CRYSTAL VCSELs WITH HIGH-INDEX-CONTRAST SUBWAVELENGTH GRATINGS
Authors: CHEN J. , FAN W. J. , WANG Q. J. , GEBSKI MARCIN , DEMS MACIEJ , CZYSZANOWSKI TOMASZ , ZHANG D. H.
Published: August 2014

Photonic crystal vertical-cavity surface-emitting laser structure with incorporation of high-index-contrast subwavelength gratings is fabricated and the three quantum well active region of the structure is investigated with 8 band k.p model. The dispersion of energy sub-bands and wave functions in the conduction bands and valence bands indicate that effective overlapping and interactions between electrons and holes can be realized in the quantum wells and that the maximum spontaneous emission rate and optical gain occurs at the expected wavelength, which is confirmed by the measured photoluminescence spectrum.
Age dating of an extensive thrust system on Mercury: implications for the planet's thermal evolution
Authors: Giacomini L. , Massironi M. , Marchi S. , Fassett C. I. , Di Achille G. , Cremonese G.
Published: August 2014

The tectonic evolution of Mercury is dominated at a global scale by contractional features such as lobate scarps that are widely distributed across the planet. These structures are thought to be the consequence of the secular cooling of Mercury. Therefore, dating these features is essential to place constraints on the timing of planetary cooling, which is important for understanding the thermal evolution of Mercury. In this work, we date an extended thrust system, which we term the Blossom Thrust System, located between 80°E and 100°E, and 30°N and 15°S, and which consists of several individual lobate scarps exhibiting a north–south orientation and a westward vergence. The age of the system was determined using several different methods. Traditional stratigraphic analysis was accompanied by crater counting of units that overlap the thrust system and by using the buffered crater-counting technique, allowing us to determine an absolute model age for the tectonic feature. These complementary methods give consistent results, implying that activity on the thrust ended between 3.5 and 3.7 Ga, depending on the adopted absolute-age model. These data provide an important insight into this portion of Mercury's crust, which may have implications for models of the thermal evolution of the planet as a whole.
Influence of deformation conditions on the development of heterogeneous recrystallization microstructures in experimentally deformed Carrara marble
Authors: Valcke S. L. A. , de Bresser J. H. P. , Pennock G. M. , Drury M. R.
Published: August 2014

Recrystallized grains are potentially useful as indicators of palaeostress in naturally deformed rocks, providing that well-calibrated relationships (palaeopiezometers) exist between the recrystallized grain size and stress. Rocks can exhibit microstructures that are heterogeneous, that is, containing recrystallized as well as deformed grains, and showing subgrains within grains that differ in size and character from the grain core to the mantle. Previous studies on palaeopiezometers only rarely took into account such heterogeneous microstructure. We used electron backscattered diffraction (EBSD) to accurately quantify the heterogeneous microstructures in experimentally deformed Carrara marble (flow stress 15–85 MPa, temperature 700–990 °C and natural strain 0.15–0.90). The sizes of bulges, recrystallized grains and deformed grains have been measured. We found that the overall character of the microstructures varies as a function of deformation conditions. In heterogeneous samples showing core-mantle microstructures, the sizes of the bulges and recrystallized grains are independent of strain and show an inverse dependency on stress. The recrystallized grains have been found to nucleate at grain boundary bulges. Our study illustrates that very different microstructures may develop in relation to the complexity of the recrystallization mechanisms. We therefore suggest that piezometers should be calibrated and applied for a single type of overall microstructure.
The TRPA1 channel is a cardiac target of mIGF-1/SIRT1 signaling
Authors: Pazienza Valerio , Pomara Cristoforo , Cappello Francesco , Calogero Raffaele , Carrara Matteo , Mazzoccoli Gianluigi , Vinciguerra Manlio
Published: August 2014

Cardiac overexpression of locally acting muscle-restricted (m)IGF-1 and the consequent downstream activation of NAD+-dependent protein deacetylase sirtuin 1 (SIRT1) trigger potent cardiac antioxidative and antihypertrophic effects. Transient receptor potential (TRP) cation channel A1 (TRPA1) belongs to the TRP ion channel family of molecular detectors of thermal and chemical stimuli that activate sensory neurons to produce pain. Recently, it has been shown that TRPA1 activity influences blood pressure, but the significance of TRPA1 in the cardiovascular system remains elusive. In the present work, using genomic screening in mouse hearts, we found that TRPA1 is a target of mIGF-1/SIRT1 signaling. TRPA1 expression is increased in the heart of cardiac-restricted mIGF-1 transgenic (Tg) mice, both in cardiomyocytes and noncardiomyocytes. In wild-type mice, SIRT1 occupied the TRPA1 promoter, inhibiting its expression, whereas in the presence of the cardiac mIGF-1 transgene, SIRT1 was displaced from the TRPA1 promoter, leading to an increase in its expression. Cardiac-specific ablation of SIRT1 (cardiac-specific knockout) in mIGF-1 Tg mice paradoxically did not increase TRPA1 expression. We have recently reported a systemic “hormetic” effect in mIGF-1 Tg mice, mild hypertension, which was depleted upon cardiac-specific knockout of SIRT1. Administration of the selective TRPA1 antagonist HC-030031 to mIGF-1 Tg mice restored blood pressure to basal levels. We identified TRPA1 as a functional target of the cardiac mIGF-1/SIRT1 signaling pathway, which may have pharmacological implications for the management of cardiovascular stress.
Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue
Authors: Majumder Rupamanjari , Pandit Rahul , Panfilov A. V.
Published: August 2014

Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model [fast inward Na+ current ( INa), L—type slow inward Ca2+ current ( ICaL), slow delayed-rectifier current ( IKs), rapid delayed-rectifier current ( IKr), inward rectifier K+ current ( IK1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is ∼2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.
A comparative study of matrix remodeling in chronic models for COPD; mechanistic insights into the role of TNF-α
Authors: Eurlings Irene M. J. , Dentener Mieke A. , Mercken Evi M. , de Cabo Rafael , Bracke Ken R. , Vernooy Juanita H. J. , Wouters Emiel F. M. , Reynaert Niki L.
Published: August 2014

Remodeling in chronic obstructive pulmonary disease (COPD) has at least two dimensions: small airway wall thickening and destruction of alveolar walls. Recently we showed comparable alterations of the extracellular matrix (ECM) compounds collagen, hyaluoran, and elastin in alveolar and small airway walls of COPD patients. The aim of this study was to characterize and assess similarities in alveolar and small airway wall matrix remodeling in chronic COPD models. From this comparative characterization of matrix remodeling we derived and elaborated underlying mechanisms to the matrix changes reported in COPD. Lung tissue sections of chronic models for COPD, either induced by exposure to cigarette smoke, chronic intratracheal lipopolysaccharide instillation, or local tumor necrosis factor (TNF) expression [surfactant protein C (SPC)-TNFα mice], were stained for elastin, collagen, and hyaluronan. Furthermore TNF-α matrix metalloproteinase (MMP)-2, -9, and -12 mRNA expression was analyzed using qPCR and localized using immunohistochemistry. Both collagen and hyaluronan were increased in alveolar and small airway walls of all three models. Interestingly, elastin contents were differentially affected, with a decrease in both alveolar and airway walls in SPC-TNFα mice. Furthermore TNF-α and MMP-2 and -9 mRNA and protein levels were found to be increased in alveolar walls and around airway walls only in SPC-TNFα mice. We show that only SPC-TNFα mice show changes in elastin remodeling that are comparable to what has been observed in COPD patients. This reveals that the SPC-TNFα model is a suitable model to study processes underlying matrix remodeling and in particular elastin breakdown as seen in COPD. Furthermore we indicate a possible role for MMP-2 and MMP-9 in the breakdown of elastin in airways and alveoli of SPC-TNFα mice.
Increased intrinsic excitability of muscle vasoconstrictor preganglionic neurons may contribute to the elevated sympathetic activity in hypertensive rats
Authors: Briant Linford J. B. , Stalbovskiy Alexey O. , Nolan Matthew F. , Champneys Alan R. , Pickering Anthony E.
Published: August 2014

Hypertension is associated with pathologically increased sympathetic drive to the vasculature. This has been attributed to increased excitatory drive to sympathetic preganglionic neurons (SPN) from brainstem cardiovascular control centers. However, there is also evidence supporting increased intrinsic excitability of SPN. To test this hypothesis, we made whole cell recordings of muscle vasoconstrictor-like (MVClike) SPN in the working-heart brainstem preparation of spontaneously hypertensive (SH) and normotensive Wistar-Kyoto (WKY) rats. The MVClike SPN have a higher spontaneous firing frequency in the SH rat (3.85 ± 0.4 vs. 2.44 ± 0.4 Hz in WKY; P = 0.011) with greater respiratory modulation of their activity. The action potentials of SH SPN had smaller, shorter afterhyperpolarizations (AHPs) and showed diminished transient rectification indicating suppression of an A-type potassium conductance ( IA). We developed mathematical models of the SPN to establish if changes in their intrinsic properties in SH rats could account for their altered firing. Reduction of the maximal conductance density of IA by 15–30% changed the excitability and output of the model from the WKY to a SH profile, with increased firing frequency, amplified respiratory modulation, and smaller AHPs. This change in output is predominantly a consequence of altered synaptic integration. Consistent with these in silico predictions, we found that intrathecal 4-aminopyridine (4-AP) increased sympathetic nerve activity, elevated perfusion pressure, and augmented Traube-Hering waves. Our findings indicate that IA acts as a powerful filter on incoming synaptic drive to SPN and that its diminution in the SH rat is potentially sufficient to account for the increased sympathetic output underlying hypertension.