Miracle-dz/UniFAR-FTUs huggingface dataset:
Ventricular repolarization in a rat model of global heart failure

Isoproterenol in high doses induces infarction‐like myocardial damage and structural and functional remodelling of the ventricular myocardium. The purpose of the present study was to investigate ventricular repolarization in a rat model of isoproterenol‐induced heart failure. Isoproterenol was administered twice to female Wistar rats (170 mg/kg, s.c., 24 h apart). Four weeks after the injections, cardiac output was measured and unipolar epicardial ventricular electrograms were recorded in situ. Activation–recovery intervals were calculated to assess repolarization. Histological examination of the heart ventricles was also performed. Heart failure in rats treated with isoproterenol was indicated by myocardial histopathological damage and reduced cardiac output. In rats with heart failure, the regional differences in activation–recovery interval prolongation over the ventricular epicardium resulted in increasing heterogeneity in the activation–recovery interval distribution and increasing repolarization heterogeneity of the ventricular subepicardium. Myocardial damage and haemodynamic changes in heart failure induced by isoproterenol were accompanied by significant changes in ventricular repolarization, which were not associated with myocardial hypertrophy.
Lethal distemper in badgers (Meles meles) following epidemic in dogs and wolves: Evidence for viral adaptation in the wildlife milieu?

Please cite this article as: Di Sabatino, Daria, Di Francesco, Gabriella, Zaccaria, Guendalina, Malatesta, Daniela, Brugnola, Luca, Marcacci, Maurilia, Portanti, Ottavio, De Massis, Fabrizio, Savini, Giovanni, Teodori, Liana, Ruggieri, Enzo, Mangone, Iolanda, Badagliacca, Pietro, Lorusso, Alessio, Lethal distemper in badgers (Meles meles) following epidemic in dogs and wolves: Evidence for viral adaptation in the wildlife milieu? , (2016), doi: 10.1016/j.meegid. 2016.10. 020
Monte Carlo simulation analysis of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin pharmacodynamics against intensive care unit‐isolated methicillin‐resistant Staphylococcus aureus

The aim of the present study was to compare the potential of ceftobiprole, dalbavancin, daptomycin, tigecycline, linezolid and vancomycin to achieve their requisite pharmacokinetic/pharmacodynamic (PK/PD) targets against methicillin‐resistant Staphylococcus aureus isolates collected from intensive care unit (ICU) settings. Monte Carlo simulations were carried out to simulate the PK/PD indices of the investigated antimicrobials. The probability of target attainment (PTA) was estimated at minimum inhibitory concentration values ranging from 0.03 to 32 μg/mL to define the PK/PD susceptibility breakpoints. The cumulative fraction of response (CFR) was computed using minimum inhibitory concentration data from the Canadian National Intensive Care Unit study. Analysis of the simulation results suggested the breakpoints of 4 μg/mL for ceftobiprole (500 mg/2 h t.i.d.), 0.25 μg/mL for dalbavancin (1000 mg), 0.12 μg/mL for daptomycin (4 mg/kg q.d. and 6 mg/kg q.d.) and tigecycline (50 mg b.i.d.), and 2 μg/mL for linezolid (600 mg b.i.d.) and vancomycin (1 g b.i.d. and 1.5 g b.i.d.). The estimated CFR were 100, 100, 70.6, 88.8, 96.5, 82.4, 89.4, and 98.3% for ceftobiprole, dalbavancin, daptomycin (4 mg/kg/day), daptomycin (6 mg/kg/day), linezolid, tigecycline, vancomycin (1 g b.i.d.) and vancomycin (1.5 g b.i.d.), respectively. In conclusion, ceftobiprole and dalbavancin have the highest probability of achieving their requisite PK/PD targets against methicillin‐resistant Staphylococcus aureus isolated from ICU settings. The susceptibility predictions suggested a reduction of the vancomycin breakpoint to 1 μg/mL.
Vasorelaxation induced by methyl cinnamate, the major constituent of the essential oil of Ocimum micranthum, in rat isolated aorta

The aim of the present study was to investigate the vascular effects of the E‐isomer of methyl cinnamate (E‐MC) in rat isolated aortic rings and the putative mechanisms underlying these effects. At 1–3000 μmol/L, E‐MC concentration‐dependently relaxed endothelium‐intact aortic preparations that had been precontracted with phenylephrine (PHE; 1 μmol/L), with an IC50 value (geometric mean) of 877.6 μmol/L (95% confidence interval (CI) 784.1–982.2 μmol/L). These vasorelaxant effects of E‐MC remained unchanged after removal of the vascular endothelium (IC50 725.5 μmol/L; 95% CI 546.4–963.6 μmol/L) and pretreatment with 100 μmol/L NG‐nitro‐l‐arginine methyl ester (IC50 749.0 μmol/L; 95% CI 557.8–1005.7 μmol/L) or 10 μmol/L 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (IC50 837.2 μmol/L; 95% CI 511.4–1370.5 μmol/L). Over the concentration range 1–3000 μmol/L, E‐MC relaxed K+‐induced contractions in mesenteric artery preparations (IC50 314.5 μmol/L; 95% CI 141.9–697.0 μmol/L) with greater potency than in aortic preparations (IC50 1144.7 μmol/L; 95% CI 823.2–1591.9 μmol/L). In the presence of a saturating contractile concentration of K+ (150 mmol/L) in Ca2+‐containing medium combined with 3 μmol/L PHE, 1000 μmol/L E‐MC only partially reversed the contractile response. In contrast, under similar conditions, E‐MC nearly fully relaxed PHE‐induced contractions in aortic rings in a Ba2+‐containing medium. In preparations that were maintained under Ca2+‐free conditions, 600 and 1000 μmol/L E‐MC significantly reduced the contractions induced by exogenous Ca2+ or Ba2+ in KCl‐precontracted preparations, but not in PHE‐precontracted preparations (in the presence of 1 μmol/L verapamil). In addition, E‐MC (1–3000 μmol/L) concentration‐dependently relaxed the contractions induced by 2 mmol/L sodium orthovanadate. Based on these observations, E‐MC‐induced endothelium‐independent vasorelaxant effects appear to be preferentially mediated by inhibition of plasmalemmal Ca2+ influx through voltage‐dependent Ca2+ channels. However, the involvement of a myogenic mechanism in the effects of E‐MC is also possible.
Transgenerational left ventricular hypertrophy and hypertension in offspring after uteroplacental insufficiency in male rats

Epidemiological studies have shown an association between low birthweight and adult disease development with transmission to subsequent generations. The aim of the present study was to examine the effect of intrauterine growth restriction in rats, induced by uteroplacental insufficiency, on cardiac structure, number, size, nuclearity, and adult blood pressure in first (F1) and second (F2) generation male offspring. Uteroplacental insufficiency or sham surgery was induced in F0 Wistar‐Kyoto pregnant rats in late gestation giving rise to F1 restricted and control offspring, respectively. F1 control and restricted females were mated with normal males, resulting in F2 control and restricted offspring, respectively. F1 restricted male offspring were significantly lighter at birth (P < 0.05), but there were no differences in birthweight of F2 offspring. Left ventricular weights and volumes were significantly increased (P < 0.05) in F1 and F2 restricted offspring at day 35. Left ventricular cardiomyocyte number was not different in F1 and F2 restricted offspring. At 6 months‐of‐age, F1 and F2 restricted offspring had elevated blood pressure (8–15 mmHg, P < 0.05). Our findings demonstrate the emergence of left ventricular hypertrophy and hypertension, with no change in cardiomyocyte number, in F1 restricted male offspring, and this was transmitted to the F2 offspring. The findings support transgenerational programming effects.
5‐Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential (ΔΨm)‐mediated apoptosis in hepatocellular carcinoma

The development of chemoresistance may reduce the efficacy of chemotherapeutic drugs for treating hepatocellular carcinoma (HCC). In the present study, the effects of apigenin on intensifying the chemosensitivity of HCC cells and an HCC xenograft model in response to 5‐fluorouracil (5‐FU) were investigated. Sub‐toxic concentrations of apigenin (4 μmol/L) significantly enhanced the cytotoxicity of 5‐FU (100 μg/mL) in HCC cells. In vivo, combined treatment with apigenin (20 mg/kg, five times/week for 3 weeks) and 5‐FU (20 mg/kg for 5 consecutive days) significantly inhibited the growth of HCC xenograft tumours. Annexin V–propidium iodide dual staining assays, terminal deoxyribonucleotidyl transferase‐mediated dUTP–digoxigenin nick end‐labelling assays and western blotting analysis were used to confirm the synergistic effects of apigenin and 5‐FU on HCC apoptosis. Coincubation of HCC cells with apigenin and 5‐FU increased levels of reactive oxygen species (ROS), which was followed by a decrease in the mitochondrial membrane potential (ΔΨm). In addition, combined triggered the mitochondrial apoptotic pathway, as indicated by decreased Bcl‐2 expression and loss of ΔΨm, with significant activation of caspase 3 and poly(ADP‐ribose) polymerase. The present study is the first to demonstrate that apigenin may potentiate the cytotoxicity of 5‐FU in HCC via inhibition of ROS‐mediated drug resistance and concurrent activation of the mitochondrial pathways of apoptosis.
Arthritis caused by Mycoplasma salivarium in hypogammaglobulinaemia.

contributing to the fall in plasma albumin concentration may have included at least two factors-namely, rehydration with crystalloid solutions as the major factor and reduced synthesis of albumin associated with impaired liver function. Previous alcoholism may have contributed. Finally, Gundersen9 showed that in healthy diabetics intravenous insulin may directly cause a reduction in the plasma albumin concentration. Our cases suggest that plasma osmotic pressure may be an important variable in patients treated by large volumes of crystalloid infusions and that further studies are required to elucidate mechanisms of pulmonary oedema in such patients. ADDENDUM-Since this paper was first submitted crystalloid infusions in diabetic ketoacidosis have been the subject of some debate.10-"3 The existence of the phenomenon of acute pulmonary oedema is not seriously disputed, but the mechanisms and frequency of its occurrence are controversial. We were unable to make any assertions about the likely mechanisms in our patients or what made them unusual, "at risk" patients. It would be surprising if the condition was limited to young ketoacidotic patients; in older patients heart failure or pneumonia is probably often diagnosed in error.
How do psychiatric patients on prison healthcare centres differ from inpatients in secure psychiatric inpatient units?

Abstract Mentally ill prisoners have consistently been highlighted as a group with complex needs. However, it is not clear what these needs are, how effective prison health services are in meeting the needs of this vulnerable group, and whether there would be any benefit to transferring them to psychiatric facilities. This study compared the characteristics and needs of mentally ill patients in prison healthcare centres (HCC prisoners) with patients in forensic medium secure psychiatric units (MSU inpatients) in the UK. HCC prisoners and MSU inpatients were in fact very similar. Where they did differ, though, was that MSU inpatients were significantly more likely to be of non-white ethnicity, diagnosed with psychotic or substance use disorders, and have recorded histories of drug misuse. HCC prisoners and MSU inpatients reported the same number of needs overall, according to the CANFOR-S (Camberwell Assessment of Need Forensic Short Version), but HCC prisoners reported significantly higher levels of unmet need. The need for transfer to alternative services was common in both groups, with bottlenecks evident at all levels. The high level of unmet need reported in the HCC prison sample is of particular clinical concern and highlights the need for improved assessment and treatment services in this setting.
Investigating the Role of Endothelial Glycogen Synthase Kinase3α/β in Atherogenesis in Low Density Lipoprotein Receptor Knockout Mice

Risk factors for developing cardiovascular disease (CVD) are associated with inflammation and endothelial activation. Activated endothelial cells (ECs) express adhesion proteins that recruit monocytes to the subendothelial layer initiating plaque development. Understanding the mechanism(s) by which ECs increase adhesion protein expression will facilitate the development of therapies aimed at preventing CVD progression and mortality. Glycogen synthase kinase (GSK)3α/β are constitutively active kinases which have been associated with many cellular pathways regulating cell viability and metabolism. While roles for myeloid GSK3α/β in the development of atherosclerosis have been established, there is limited knowledge on the potential roles of endothelial GSK3α/β. With the use of Cre recombinase technology, GSK3α/β was knocked out of both ECs and macrophages (Tie2Cre GSK3α/βfl/fl LDLR−/−). A bone marrow transplant was used to replenish GSK3α/β in the myeloid lineage allowing the assessment of an endothelial-selective GSK3α/β knockout (BMT Tie2Cre GSK3α/βfl/fl LDLR−/−). In both models, adhesion protein expression, macrophage recruitment and plaque volume were reduced in GSK3α knockout mice. GSK3β knockout had no significant effect. Results from this study are the first to suggest a pro-atherogenic role of endothelial GSK3α and support existing evidence for targeting GSK3α in the treatment of atherosclerotic CVD.
Knowledge and vaccination status of hepatitis B amongst medical interns of Rural Medical College, Loni, Maharashtra, India

Hepatitis B Virus (HBV) infection is a serious global public health problem. It is the most common blood borne viral infection which places healthcare professional at higher occupational risk. The present study was conducted to assess the current knowledge and vaccination status about hepatitis B amongst medical interns. A cross-sectional study was conducted between February and March 2009 on 100 medical interns of the Rural Medical College, Loni, India. A pre-designed questionnaire which assessed their knowledge of hepatitis B was the tool of data collection. The data was analyzed in the form of percentage and proportions, and the chi-square test was applied. In the present study, 83.3% of interns showed a good level of knowledge regarding hepatitis B infection. The percentage of interns with the correct knowledge regarding post exposure prophylaxis and mode of transmission of hepatitis B were 89% and 90% respectively. It was found that 87% of the respondents espoused vaccination as a measure for the prevention of hepatitis B and 72% of the interns were fully immunized against hepatitis B. However, there is a misconception about prophylaxis, vaccination and the treatment of HBV. Hence there is an imperative need for health education to improve the knowledge of the interns towards hepatitis B infection. DOI: http://dx.doi. org/10.3329/seajph.v3i2. 20034 South East Asian Journal of Public Health Vol.3(2) 2013: 19-22
CaMKIIδ and cardiomyocyte Ca2+ signalling new perspectives on splice variant targeting

Control of cardiomyocyte cytosolic Ca2+ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca2+, Ca2+/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca2+ channels/transporters. CaMKII is primarily expressed either in the δB or δC splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca2+ levels promote the binding of a Ca2+/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδB/δC variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca2+ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδB in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδC. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδB, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca2+ uptake and maintain cytosolic Ca2+ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.
High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya

Although malaria is widely considered a major cause of death in young children born with sickle cell anemia (SCA) in sub-Saharan Africa, this is poorly quantified. We attempted to investigate this question through 4 large case-control analyses involving 7164 children living on the coast of Kenya. SCA was associated with an increased risk of admission to hospital both with nonmalaria diseases in general (odds ratio [OR] = 4.17; 95% confidence interval [CI], 1.95-8.92; P < .001) and with invasive bacterial diseases in particular (OR = 8.73; 95% CI, 4.51-16.89; P < .001). We found no evidence for a strongly increased risk of either uncomplicated malaria (OR = 0.43; 95% CI, 0.09-2.10; P = .30) or malaria complicated by a range of well-described clinical features of severity (OR = 0.80; 95% CI, 0.25-2.51; P = .70) overall; nevertheless, mortality was considerably higher among SCA than non-SCA children hospitalized with malaria. Our findings highlight both the central role that malaria plays in the high early mortality seen in African children with SCA and the urgent need for better quantitative data. Meanwhile, our study confirms the importance of providing all children living with SCA in malaria-endemic areas with effective prophylaxis.
Inability of trained nurses to perform basic life support.

by more than 20%o ofthe baseline value participated in the remainder ofthe study. On two occasions subjects inhaled single blind 4 ml solutions of isotonic saline' and of nebulised isotonic ipratropium bromide free of benzalkonium chloride or edetic acid and had their FEVy measured over 60 minutes. On two further occasions they inhaled double blind 4 ml solutions ofincreasing concentrations of nebulised benzalkonium chloride (0-125 to 5-0 g/l) or edetic acid (0-25 to 10-0 g/l) until the FEV1 had fallen by >20%. All solutions were nebulised by compressed air using an Inspiron nebuliser at a flow rate of 8 I/min. The aerosol was inhaled through a mouthpiece during tidal breathing from a starting volume of4 ml in the nebuliser to dryness. The airway response was expressed as percentage change in FEV, from the baseline value, and the differences between the challenge solutions were evaluated by analysis ofvariance and application ofthe Newman-Keul's test. The PC20 FEVy values (cumulative concentration of benzalkonium chloride or edetic acid causing a 20% fall in FEV1) were obtained from each concentration-response curve and geometric mean values calculated for the group. There was no significant difference between the baseline FEV, measurements on the different study days. After inhaling 4 ml Atrovent six patients developed bronchoconstriction with a mean (SEM) fall in FEV1 of 35 3 (5 4)% two minutes after inhalation (figure). When these six subjects inhaled 4 ml preservative free ipratropium bromide solution all showed bronchodilatation, the mean FEV1 increasing to 112-3 (4-9)% of baseline at two minutes (figure). Inhalation of 4 ml saline produced no significant change in airway calibre. The change in FEVI after inhaling Atrovent was significantly different from that after inhaling preservative free ipratropium bromide at all time points after inhalation (p<0 05) and from the response after saline for the first 30 minutes (p<0 05). 120 si 100 80 0 2 5 10 15 30 45 60 Time (min) Changes in airway calibre after inhalation of nebulised Atrovent (A), preservative free ipratropium bromide (0) and saline (A) in the six asthmatic subjects in whom the FEV1 fell >200% after inhalation of4 ml solution ofnebulised Atrovent. Each point represents the mean FEVy expressed as per cent of baseline, and each bar the SEM. Inhalation of the preservatives administered separately produced dose related bronchoconstriction, which persisted for longer than 60 minutes. The cumulative geometric mean (range) PC20 FEV1 was 0 30 g/l (0-13-2-0) …
Estimation of Aqueous Solubility for a Diverse Set of Organic Compounds Based on Molecular Topology

An accurate and generally applicable method for estimating aqueous solubilities for a diverse set of 1297 organic compounds based on multilinear regression and artificial neural network modeling was developed. Molecular connectivity, shape, and atom-type electrotopological state (E-state) indices were used as structural parameters. The data set was divided into a training set of 884 compounds and a randomly chosen test set of 413 compounds. The structural parameters in a 30-12-1 artificial neural network included 24 atom-type E-state indices and six other topological indices, and for the test set, a predictive r2 = 0.92 and s = 0.60 were achieved. With the same parameters the statistics in the multilinear regression were r2 = 0.88 and s = 0.71, respectively.
Historical, Political, and Technological Context Associated with Early Identification of Hearing Loss

1. In 1978, there were only three states with legislative mandates for newborn hearing screening; now there are 16 and the number is growing rapidly (see J. Johnson et al. in this issue of Seminars) 2. For the first time, the federal government has set a specific goal to lower the average age at which hearing impairment is identified instead of just talking about its importance (see U.S. Department of Health and Human Services, p. 460); and 3. A new National Institute on Deafness and Other Communicative Disorders was recently established and has outlined a national strategic research plan that identifies "improved methods for early screening and diagnosis of hearing loss in infants and young children" (p. 63) as one of its primary goals. After many years of inadequate progress, it appears that the commitment and the technology to identify hearing impairment in infants and toddlers has reached the point where real progress is possible. However, to understand how best to proceed, it is important to know the historical, political, and technological context for early identification of hearing loss. This article will: (1) review the prevalence and consequences of hearing loss in childhood, (2) trace the governmental history of initiatives for early identification of hearing loss in the United States, (3) examine the general criteria for screening for medical disorders and their application to neonatal hearing screening, and (4) summarize the advantages and disadvantages of the available neonatal hearing screening techniques.