tbuckley/cabot-search huggingface dataset:
First imported Plasmodium ovale malaria in Central America: case report of a Guatemalan soldier and a call to improve its accurate diagnosis
Authors: María Eugenia Castellanos, Sheilee Díaz, Emily Parsons, Leonard F Peruski, Fabiola Enríquez, Juan Luis Ramírez, Norma Padilla
Journal: Military Medical Research (2015)

The Mesoamerican Ministers of Health have set 2020 as the target for malaria elimination to be achieved in the region. Imported malaria cases are a potential threat to countries attempting elimination or working to prevent resurgence. We report the first imported Plasmodium ovale infection with molecular confirmation in Central America, which occurred in a Guatemalan soldier that had been deployed in Africa. The obstacles for its diagnosis using the standard microscopy technique and the need to improve its detection are discussed.
Independent Genome Reduction and Phylogenetic Reclassification of the Oceanic SAR11 Clade
Authors: J. Viklund, T. J. G. Ettema, S. G. E. Andersson
Journal: Molecular Biology and Evolution (2011)

The SAR11 clade, here represented by Candidatus Pelagibacter ubique, is the most successful group of bacteria in the upper surface waters of the oceans. In contrast to previous studies that have associated the 1.3 Mb genome of Ca. Pelagibacter ubique with the less than 1.5 Mb genomes of the Rickettsiales, our phylogenetic analysis suggests that Ca. Pelagibacter ubique is most closely related to soil and aquatic Alphaproteobacteria with large genomes. This implies that the SAR11 clade and the Rickettsiales have undergone genome reduction independently. A gene flux analysis of 46 representative alphaproteobacterial genomes indicates the loss of more than 800 genes in each of Ca. Pelagibacter ubique and the Rickettsiales. Consistent with their different phylogenetic affiliations, the pattern of gene loss differs with a higher loss of genes for repair and recombination processes in Ca. Pelagibacter ubique as compared with a more extensive loss of genes for biosynthetic functions in the Rickettsiales. Some of the lost genes in Ca. Pelagibacter ubique, such as mutLS, recFN, and ruvABC, are conserved in all other alphaproteobacterial genomes including the small genomes of the Rickettsiales. The mismatch repair genes mutLS are absent from all currently sequenced SAR11 genomes and also underrepresented in the global ocean metagenome data set. We hypothesize that the unique loss of genes involved in repair and recombination processes in Ca. Pelagibacter ubique has been driven by selection and that this helps explain many of the characteristics of the SAR11 population, such as the streamlined genomes, the long branch lengths, the high recombination frequencies, and the extensive sequence divergence within the population.
Influence of Donor and Recipient HLA Locus Mismatching on Development of Obliterative Bronchiolitis after Lung Transplantation
Authors: LARRY L. SCHULMAN, ALAN D. WEINBERG, CARLTON C. McGREGOR, NICOLE M. SUCIU-FOCA, SILVIU ITESCU
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Obliterative bronchiolitis (OB) after lung transplantation is the end result of multiple immunologic, virologic, genetic, and environmental effects on the transplanted lung. In this study, we first analyzed risk factors for OB in a single-center population of 152 lung transplant recipients. We then examined the influence of donor and recipient HLA mismatching on progression to OB, and on the identified risk factors for OB. The median time to onset of OB for the entire study population was 2.7 yr. The significant risk factors for OB by multivariate analyses were grade A2 or A3 acute rejection (p = 0.0126) and cytomegalovirus (CMV) pneumonitis (p = 0.0358). The only significant HLA risk factor for OB was mismatching at the HLA-A locus (p = 0.0144). On the basis of Cox proportional hazards modeling, a predictive formula was derived to estimate the risk of OB after lung transplantation. Although mismatching at the HLA-DR locus was a significant risk factor for CMV pneumonitis in recipients exposed to CMV before transplantation (p = 0.0199), and protected against acute rejection, it did not independently protect against OB. These results indicate that HLA mismatches between donors and recipients significantly influence the development of OB both directly, and indirectly, by influencing the major risk factors for OB.
Survival of Patients Undergoing Hemodialysis with Paricalcitol or Calcitriol Therapy
Authors: Ming Teng, Myles Wolf, Edmund Lowrie, Norma Ofsthun, J. Michael Lazarus, Ravi Thadhani
Journal: New England Journal of Medicine (2003)

Elevated calcium and phosphorus levels after therapy with injectable vitamin D for secondary hyperparathyroidism may accelerate vascular disease and hasten death in patients undergoing long-term hemodialysis. Paricalcitol, a new vitamin D analogue, appears to lessen the elevations in serum calcium and phosphorus levels, as compared with calcitriol, the standard form of injectable vitamin D.We conducted a historical cohort study to compare the 36-month survival rate among patients undergoing long-term hemodialysis who started to receive treatment with paricalcitol (29,021 patients) or calcitriol (38,378 patients) between 1999 and 2001. Crude and adjusted survival rates were calculated and stratified analyses were performed. A subgroup of 16,483 patients who switched regimens was also evaluated.The mortality rate among patients receiving paricalcitol was 3417 per 19,031 person-years (0.180 per person-year), as compared with 6805 per 30,471 person-years (0.223 per person-year) among those receiving calcitriol (P<0.001). The difference in survival was significant at 12 months and increased with time (P<0.001). In the adjusted analysis, the mortality rate was 16 percent lower (95 percent confidence interval, 10 to 21 percent) among paricalcitol-treated patients than among calcitriol-treated patients. A significant survival benefit was evident in 28 of 42 strata examined, and in no stratum was calcitriol favored. At 12 months, calcium and phosphorus levels had increased by 6.7 and 11.9 percent, respectively, in the paricalcitol group, as compared with 8.2 and 13.9 percent, respectively, in the calcitriol group (P<0.001). The two-year survival rate among patients who switched from calcitriol to paricalcitol was 73 percent, as compared with 64 percent among those who switched from paricalcitol to calcitriol (P=0.04).Patients who receive paricalcitol while undergoing long-term hemodialysis appear to have a significant survival advantage over those who receive calcitriol. A prospective, randomized study is critical to confirm these findings.
Thyroid hormone-induced alterations in phospholamban protein expression. Regulatory effects on sarcoplasmic reticulum Ca2+ transport and myocardial relaxation.
Authors: E Kiss, G Jakab, E G Kranias, I Edes
Journal: Circulation Research (1994)

The aim of the present study was to determine the changes in phospholamban protein levels and their regulatory effect on sarcoplasmic reticulum (SR) Ca2+ uptake and left ventricular function in hypothyroid and hyperthyroid rat hearts. Hypothyroidism was associated with decreases in basal left ventricular function (+dP/dt and -dP/dt), whereas in hyperthyroidism these parameters were elevated compared with values for euthyroid hearts. The maximal SR Ca2+ uptake rates were 12.8 +/- 1.1, 15.5 +/- 1.2, and 21.4 +/- 1.4 nmol Ca2+ per milligram per minute, and the EC50 values for Ca2+ were 0.76 +/- 0.09, 0.41 +/- 0.07, and 0.30 +/- 0.05 mumol/L assayed in homogenates from hypothyroid, euthyroid, and hyperthyroid hearts, respectively. The relative tissue level of phospholamban was increased (135%) in hypothyroidism and decreased (75%) in hyperthyroidism compared with euthyroidism (100%). An opposite trend was observed for the SR Ca(2+)-ATPase, which was depressed (74%) in hypothyroid hearts but increased (134%) in hyperthyroid hearts. Consequently, the relative ratio of phospholamban to Ca(2+)-ATPase was highest in hypothyroid and lowest in hyperthyroid hearts, and these changes correlated with changes in the EC50 of the SR Ca2+ uptake for Ca2+. Stimulation of hearts with 0.1 mumol/L isoproterenol revealed that the relaxant effects were lower in hyperthyroid hearts and higher in hypothyroid hearts compared with euthyroid hearts, consistent with the alterations in the phospholamban levels. The maximal increases in the speed of relaxation, elicited by isoproterenol stimulation, correlated with the changes in the relative ratio of phospholamban to Ca(2+)-ATPase in these hearts.(ABSTRACT TRUNCATED AT 250 WORDS)
Aquaporin 7: the glycerol aquaeductus in the heart
Authors: M. Gladka, H. el Azzouzi, L. J. De Windt, P. A. da Costa Martins
Journal: Cardiovascular Research (2009)

Deprivation of available energy has been postulated to play a major role in the genesis of heart failure,1–3 and accumulating evidence points to the premise that changes in gene expression that alter energy metabolism weaken the heart muscle,4,5 reinforcing the logic of ameliorating energy substrates, and/or metabolism as a heart failure therapeutic. Reduced cardiac energy levels, in turn, influence a plethora of cardiac events, including free radical defense mechanisms which lower cardiomyocyte survivability,6 cardiac contractility,7 adverse remodelling and arrhythmogenic susceptibility.8

The heart is able to produce energy from a wide range of substrates and shifts continuously between sources, according to supply availability as controlled by exercise, nutritional status, or pathophysiological conditions. Therefore, the immediate cardiac capacity to produce energy and to adapt its metabolism to requirement changes is a crucial cardiac functional parameter. ATP is the direct source of energy for all energy-consuming reactions in the heart (pump function, Ca2+ re-uptake into the sarcoplasmic reticulum and maintenance of the sarcolemmal ion gradients). In the healthy adult heart, more than 70% of the energy required is covered by fatty acid oxidation in mitochondria, with the remaining 30% being accounted for by carbohydrate oxidation, mainly using glucose and ketone bodies as exogenous substrates.9–11 Under conditions of high ATP demand relative to ATP availability, the myocyte is able to recruit additional pathways or depend more heavily on alternative pathways for … 

*Corresponding author. Tel: +31 30 253 8900; fax: +31 30 253 9036. E-mail address : p.a.dacostamartins{at}umcutrecht.nl
Conditional Neuronal Nitric Oxide Synthase Overexpression Impairs Myocardial Contractility
Authors: Natalie Burkard, Adam G. Rokita, Susann G. Kaufmann, Matthias Hallhuber, Rongxue Wu, Kai Hu, Ulrich Hofmann, Andreas Bonz, Stefan Frantz, Elizabeth J. Cartwright, Ludwig Neyses, Lars S. Maier, Sebastian K.G. Maier, Thomas Renné, Kai Schuh, Oliver Ritter
Journal: Circulation Research (2007)

The role of the neuronal NO synthase (nNOS or NOS1) enzyme in the control of cardiac function still remains unclear. Results from nNOS(-/-) mice or from pharmacological inhibition of nNOS are contradictory and do not pay tribute to the fact that probably spatial confinement of the nNOS enzyme is of major importance. We hypothesize that the close proximity of nNOS and certain effector molecules like L-type Ca(2+)-channels has an impact on myocardial contractility. To test this, we generated a new transgenic mouse model allowing conditional, myocardial specific nNOS overexpression. Western blot analysis of transgenic nNOS overexpression showed a 6-fold increase in nNOS protein expression compared with noninduced littermates (n=12; P<0.01). Measuring of total NOS activity by conversion of [(3)H]-l-arginine to [(3)H]-l-citrulline showed a 30% increase in nNOS overexpressing mice (n=18; P<0.05). After a 2 week induction, nNOS overexpression mice showed reduced myocardial contractility. In vivo examinations of the nNOS overexpressing mice revealed a 17+/-3% decrease of +dp/dt(max) compared with noninduced mice (P<0.05). Likewise, ejection fraction was reduced significantly (42% versus 65%; n=15; P<0.05). Interestingly, coimmunoprecipitation experiments indicated interaction of nNOS with SR Ca(2+)ATPase and additionally with L-type Ca(2+)- channels in nNOS overexpressing animals. Accordingly, in adult isolated cardiac myocytes, I(Ca,L) density was significantly decreased in the nNOS overexpressing cells. Intracellular Ca(2+)-transients and fractional shortening in cardiomyocytes were also clearly impaired in nNOS overexpressing mice versus noninduced littermates. In conclusion, conditional myocardial specific overexpression of nNOS in a transgenic animal model reduced myocardial contractility. We suggest that nNOS might suppress the function of L-type Ca(2+)-channels and in turn reduces Ca(2+)-transients which accounts for the negative inotropic effect.
Assessment of bronchial reactivity by forced oscillation admittance avoids the upper airway artefact
Authors: R. Farré, M. Rotger, F Marchal, R Peslin, D. Navajas
Journal: European Respiratory Journal (1999)

The forced oscillation technique (FOT) allows easy assessment of bronchial reactivity. The use of a standard FOT generator (SG) results in changes in respiratory system resistance (delta Rrs,SG) which are affected by an artefact caused by the extrathoracic upper airway (EUA). The aim was to improve the FOT assessment of bronchial reactivity with the SG by computing the change in FOT admittance (delta Ars,SG), which is theoretically unaffected by this artefact. Delta Rrs,SG and delta Ars,SG after bronchial challenge in 17 children were compared with the values measured with a head generator (HG) FOT setup (delta Rrs,HG and delta Ars,HG, respectively), which were taken as a reference, since HG provides data virtually freed from the EUA artefact. At 10 Hz, the SG significantly underestimated the resistance change: delta Rrs,SG=1.77+/-0.62 versus delta Rrs,HG=6.09+/-1.23 hPa x L(-1) x s. Delta Rrs,SG and delta Rrs,HG did not show a significant correlation. By contrast, the amplitude of the change in admittance measured by SG was close to the one obtained with the reference HG: /delta Ars,SG/=29.5+/-4.6 versus /delta Ars,HG/=32.7+/-3.9 mL x hPa(-1) x s(-1). /Delta Ars,SG/ and /delta Ars,HG/ showed a significant correlation (r=0.65, p>0.01). Similar results were found up to 20 Hz. The extrathoracic upper airway artefact was minimized when computing the change in admittance with the standard generator. This forced oscillation technique index may improve the sensitivity in assessing bronchial reactivity with the standard generator setup, which is the most common and easiest to use method for routine lung function testing.
The volatile metabolic fingerprint of ventilator-associated pneumonia
Authors: Lieuwe D. J. Bos, Ignacio Martin-Loeches, Janine B. Kastelijn, Gisela Gili, Mateu Espasa, Pedro Povoa, Arend H. J. Kolk, Hans-Gerd Janssen, Peter J. Sterk, Antonio Artigas, Marcus J. Schultz
Journal: Intensive Care Medicine (2014)
Seizures in low-grade gliomas: natural history, pathogenesis, and outcome after treatments
Authors: Roberta Rudà, Lorenzo Bello, Hugues Duffau, Riccardo Soffietti
Journal: Neuro-Oncology (2012)

Seizures represent a common symptom in low-grade gliomas; when uncontrolled, they significantly contribute to patient morbidity and negatively impact quality of life. Tumor location and histology influence the risk for epilepsy. The pathogenesis of tumor-related epilepsy is multifactorial and may differ among tumor histologies (glioneuronal tumors vs diffuse grade II gliomas). Gross total resection is the strongest predictor of seizure freedom in addition to clinical factors, such as preoperative seizure duration, type, and control with antiepileptic drugs (AEDs). Epilepsy surgery may improve seizure control. Radiotherapy and chemotherapy with alkylating agents (procarbazine + CCNU+ vincristine, temozolomide) are effective in reducing the frequency of seizures in patients with pharmacoresistant epilepsy. Newer AEDs (levetiracetam, topiramate, lacosamide) seem to be better tolerated than the old AEDs (phenobarbital, phenytoin, carbamazepine), but there is lack of evidence regarding their superiority in terms of efficacy.
Cooperative Study of Hospital Frequency and Character of Transient Ischemic Attacks
Authors: P. Michael Conneally
Journal: JAMA (1978)

A total of 969 (73%) of 1,328 patients with cases of suspected transient ischemic attacks (TIAs) who came to six institutions during a 21-month period were followed up. Factors were identified and prospectively analyzed for risk for further TIAs, stroke, and deatn. A history of multiple carotid artery TIAs was significantly related to further TIAs. A single TIA placed the patient at greater risk for early infarction. Older age, male sex, and unreliability to take dangerous medication were risk factors for cerebral infarction. Anticoagulant therapy, older age, male sex, diabetes mellitus, heart disease, abnormal ECG, and poor surgical risk were factors for death. The increased mortality associated with anticoagulants was confined to the older age group. While white patients treated with antiplatelet-aggregating agents had a lower mortality than those treated otherwise, this was not true amont black patients.
Liver specific deletion of CYLDexon7/8 induces severe biliary damage, fibrosis and increases hepatocarcinogenesis in mice
Authors: Toni Urbanik, Regina Johanna Boger, Thomas Longerich, Katharina Becker, Karl Roland Ehrenberg, Nadine Hövelmeyer, Matthias Hahn, Marcus Schuchmann, Dirk Jäger, Ari Waisman, Marcus Alexander Wörns, Henning Schulze-Bergkamen
Journal: Journal of Hepatology (2012)
Phagocyte nicotinamide adenine dinucleotide phosphate oxidase activity in patients with inherited IFN-γR1 or IFN-γR2 deficiency
Authors: Francesca Conti, Walmir Cutrim Aragão Filho, Carolina Prando, Caroline Deswarte, Marjorie Hubeau, Peter E. Newburger, Jean-Laurent Casanova, Jacinta Bustamante, Antonio Condino-Neto
Journal: Journal of Allergy and Clinical Immunology (2014)
Longitudinal Assessment of Premorbid Cognitive Functioning in Patients With Schizophrenia Through Examination of Standardized Scholastic Test Performance
Authors: Rebecca Fuller, Peg Nopoulos, Stephan Arndt, Dan O’Leary, Beng-Choon Ho, Nancy C. Andreasen
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Studies suggest the presence of premorbid cognitive impairment in patients with schizophrenia, yet the onset and course of these deficits remain unclear. The purpose of this study was to investigate the longitudinal course of premorbid cognitive functioning in individuals with schizophrenia by using prospective data obtained from scholastic test results. METHOD: Scores from grades 4, 8, and 11 on the Iowa Tests of Basic Skills and the Iowa Tests of Educational Development were obtained for 70 subjects who later developed schizophrenia. The mean percentile rank of the subjects' scores in the areas of vocabulary, reading comprehension, language, mathematics, sources of information, and an overall composite category were compared with state norms. RESULTS: The subjects scored below the 50th percentile for each category in all three grades, but only language, reading, sources of information, and composite scores from grade 11 were significantly below state norms. With regard to longitudinal course, there was a significant linear decrease in language scores over time. Scores from grade 11 were positively correlated with WAIS-R IQ, verbal fluency, and Rey Auditory Verbal Learning scores at first illness episode. Scores from grade 11 were not significantly correlated with age at illness onset or ratings of disorganized, psychotic, or negative symptoms. CONCLUSIONS: Scholastic test scores at grades 4 and 8 were nonsignificantly below average in this group of children who later developed schizophrenia. However, test scores dropped significantly between grades 8 and 11. This corresponds to ages 13–16 years, or the onset of puberty. Poor or declining scholastic performance may be a precursor to the cognitive impairment seen during the first episode of illness.
Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand–Induced Apoptosis Is Inhibited by Bcl-2 but Restored by the Small Molecule Bcl-2 Inhibitor, HA 14-1, in Human Colon Cancer Cells
Authors: Frank A. Sinicrope, Robert C. Penington, Xi Ming Tang
Journal: Clinical Cancer Research (2004)

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent that induces apoptosis in multiple tumor cell types while sparing most normal cells. We determined the effect of ectopic Bcl-2 expression on TRAIL-induced apoptosis and whether the small molecule Bcl-2 inhibitor, HA14-1, could increase TRAIL sensitivity.SW480 human colon cancer cells were stably transfected with the PC3-Bcl-2 plasmid or vector alone. Cells were incubated with recombinant human TRAIL +/- HA14-1 or caspase-9 inhibitor (Z-LEHD-FMK). Apoptosis was analyzed by Annexin V-fluorescein isothiocyanate labeling and DNA fragmentation factor 45 (DFF45) cleavage. Clonigenic survival was also studied. Caspase activation was determined by immunoblotting or colorimetric assay. The cytosolic expression of Bid, Bax, and XIAP and release of cytochrome c and Smac/DIABLO were determined by immunoblotting.Bcl-2 overexpression partially protected SW480 cells from a dose-dependent induction of apoptosis by TRAIL, as did a caspase-9 inhibitor, and increased their clonogenic survival. Bcl-2 overexpression attenuated TRAIL-induced cleavage of caspase-8, indicating its activation upstream and downstream of mitochondria, as well as cleavage of Bid and caspase-3. Bcl-2 inhibited TRAIL-induced Bax translocation, cytosolic release of cytochrome c and Smac/DIABLO, and the downstream cleavage of XIAP and DFF45. Coadministration of HA14-1 and TRAIL increased apoptosis in SW480/Bcl-2 cells by restoring Bax redistribution and cytochrome c release.Bcl-2 confers apoptosis resistance to TRAIL by inhibiting a mitochondrial amplification step and by inactivating downstream XIAP in SW480 cells. HA14-1 reversed Bcl-2-mediated TRAIL resistance, suggesting a novel strategy for increasing TRAIL sensitivity in Bcl-2-overexpressing colon cancers.
The use of perioperative intravenous sildenafil in patients with mitral valve disease and co-existent pulmonary hypertension during cardiac surgery
Authors: B.P. Madden, S. Sharma, E. Holden, Y. Looney, S.N. Fletcher, A. Sheth
Journal: European Respiratory Journal (2011)

Introduction: Patients who have mitral valve (MV) disease with associated pulmonary hypertension (PH) may develop acute rises in pulmonary vascular resistance (PVR) perioperatively.Such pulmonary hypertensive crises may significantly increase perioperative morbidity and mortality. Although there is limited experience with agents to reduce the PVR, their use may be associated with systemic hypotension.

Aim: To evaluate the safety and haemodynamic effects of intravenous (IV) sildenafil perioperatively, in patients with PH and MV disease undergoing cardiac surgery.

Method: Nine patients, two males and seven females, age range 64 to 81 (median 76) years, with PH, mean pulmonary artery pressure range 30 to 56 (median 43) mmHg, associated with MV disease, who had MV surgery, received IV sildenafil (1mg/ml) at a rate of 1mg/kg for one hour in the immediate post operative period.Pulmonary and systemic haemodynamic measurements were recorded at ten-minute intervals.

Results: A statistically significant reduction (p=0.006) in PVR was observed.There was a trend towards improvement in the cardiac index (CI), although it did not reach statistical significance (p=0.059).Mean systemic arterial pressure remained stable and no detrimental effect on other haemodynamic parameters was noted.

Discussion: Our study suggests that perioperative use of IV sildenafil is safe and not associated with systemic hypotension.We observed a favourable response in PVR and a trend towards improvement in CI.We suggest that IV sildenafil should be considered for selected patients with MV disease and PH who require MV surgery.