Miracle-dz/UniFAR-FTUs huggingface dataset:
Moderate hypothermia during ex vivo machine perfusion promotes recovery of hearts donated after cardiocirculatory death†.

OBJECTIVES To establish the optimal machine perfusion temperature for recovery of hearts in a rodent model of donation after declaration of cardiocirculatory death (DCD). METHODS Hearts from male Lewis rats (n = 14/group) were subjected to 25 min of in situ warm (37°C) ischaemia to simulate DCD. They were then explanted and reperfused with diluted autologous blood for 60 min at 20, 25, 30, 33 or 37°C, after which they were stored at 0-4°C in Custodiol preservation solution for 240 min. Fresh-excised and cold-stored ischaemic hearts were used as controls. The viability of the different groups was assessed by comparing heart rate and left ventricular contractility in a Langendorff circuit, as well as perfusate levels of troponin-t and creatine kinase (CK), and myocardial levels of adenosine triphosphate (ATP) and reduced glutathione. RESULTS During ex vivo reperfusion, hearts in all groups resumed beating within minutes. The mean heart rate was highest in the 37°C group at 154.72 ± 33.01 beats × min(-1) (bpm), and declined in proportion to temperature to 39.72 ± 5.53 bpm at 20°C. Troponin-t levels were highest in the 37°C group (79.49 ± 20.79 µg/l), the values were significantly lower in all other reconditioned groups with a minimum of 12.472 ± 7.08 µg/l in the 20°C group (P < 0.0001). Tissue ATP levels ranged from 4.32 ± 1.71 µmol/g at 33°C to 4.59 ± 1.41 µmol/g at 30°C, all significantly higher than the mean ATP level of 1.41 ± 0.93 µmol/g in untreated ischaemic hearts (P < 0.0001). During Langendorff assessment, the mean heart rate and contractility of all groups were higher than those of cold-stored ischaemic hearts (P < 0.0001), yet not significantly different from those of fresh controls. The perfusate levels of troponin-t and CK, and myocardial levels of reduced-glutathione and ATP were not significantly different between groups. CONCLUSION Our results suggest that mild hypothermia during ex vivo reperfusion improves recovery of ischaemic hearts in a rodent DCD model.
Relationship Between Retinal and Glomerular Lesions in IDDM Patients

Current knowledge regarding the concordance and discordance of the eye and kidney complications of diabetes is based on observations by ophthalmoscopy of retinal structural changes, which may be present at early stages of the disorder, and renal functional changes, which only become apparent at the later stages of the disease. For this reason we investigated the relationship between retinal structural lesions and quantitative measures of glomerular structure in patients with insulin-dependent diabetes mellitus (IDDM). Renal biopsies were evaluated using morphometric techniques, and retinopathy classification was determined by retinal fundus photography in 86 patients with IDDM: age 30.4 ± 7.3 years and duration of IDDM 18.9 ± 6.3 years (mean ± SD). Retinopathy score correlated with glomerular basement membrane width (r = 0.39, P = 0.0002), mesangial volume fraction (VvMes/Glom) (r = 0.35, P = 0.0009), surface density of the peripheral capillary wall (SvPGBM/Glom) (r = 0.34, P = 0.0013), and index of arteriolar hyalinosis (r = 0.36, P = 0.0008). Abnormalities in VvMes/Glom and SvPGBM/Glom were more pronounced in patients with both retinopathy and hypertension. Four of the 15 patients (27%) with either normal urinary albumin excretion (UAE) or low-level microalbuminuria had advanced retinopathy but normal VvMes/Glom. In conclusion, the presence of advanced retinal disease with or without hypertension in patients with IDDM indicates a greater likelihood of advanced nephropathy as evidenced by increased VvMes/Glom and decreased SvPGBM/Glom. However, marked discordance between retinopathy and nephropathy occurs, as illustrated by patients with normal UAE or low-level microalbuminuria, normal glomerular structural measures, and advanced retinopathy.
Stereotactic pallidotomy for Parkinson's disease

Eleven patients suffering from Parkinson's disease were followed for up to 4 years after unilateral pallidotomy. We observed persistent contralateral improvement and unexpected ipsilateral improvement of motor symptoms. In addition, there was a protracted relief of contralateral dyskinesias and maintenance of relatively stable levodopa dosage.
Structural complexity of territories: preference, use of space and defence in commensal house mice, Mus domesticus


Previous studies suggest the physical structure of a habitat has profound effects on intraspecific competition and spacing behaviour among small mammals. We compared habitat preferences and the exploratory behaviour and aggressive territorial defence of male house mice in three types of enclosure differing only in their degree of structural complexity. Each enclosure contained a nestbox placed in one corner, a central food hopper and 10 house bricks. The bricks were either placed around the outer walls (open enclosures), lined up across the middle (wall enclosures) or scattered separately across the floor (complex enclosures). In pairwise choice tests, mice showed a strong preference for wall or complex enclosures over open enclosures but no preference between wall and complex enclosures. They were more active throughout the enclosure with complex structuring and stayed near the side walls in open enclosures. Residents in open enclosures initially showed a lower rate of attack and duration of pursuit when faced with an intruder but not when faced with a second intruder. In complex enclosures, nearly all encounters ended because the residents continued pursuit but lost track of the intruder. This occurred in only half of intruder pursuits in open and wall enclosures. Our results suggest that mice prefer areas containing physical structure because this provides a degree of protection from predators but territories with complex physical structuring appear to be much more difficult to defend. Complex areas may thus support a higher density of mice than open areas or those with more simply aligned physical structuring. Copyright 2000 The Association for the Study of Animal Behaviour.
Defective oxidative metabolism of rat liver mitochondria in hemorrhagic and endotoxin shock.

MELA, LEENA, LEONARDO V. BACALZO, JR., AND LEONARD D. MILLER. Defective oxidatiue metabolism of rat liver mitochondria in hemorrhagic and endotoxin shock. Am. J. Physiol. 220(2) : 571477. 197 1 . -Rat liver mitochondrial functions were studied after hemorrhagic hypovolemia and Escherichia coli endotoxin shock. The respiratory activity in State 4 was increased indicating normal utilization of substrates and oxygen, but loose coupling. The electron-transfer reactions induced by substrates were unaltered. The respiratory rates in State 3, however, were inhibited in the presence of any of the substrates used, succinate, glutamate-malate, or aketoglutarate. Due to increased State 4 and decreased State 3 rates, the respiratory control ratios dropped from control values of 6-8 to about 2. The ADP utilization rate decreased parallel with the respiratory rates. Also, an addition of ADP to mitochondria prepared at final stages of shock failed to induce steady-state changes of the cytochromes. The mitochondrial uncoupler-sensitive ATPase activity was inhibited as well by 7075. All these alterations occurred both in hemorrhagic and endotoxin shock. The only significant difference was the dependence of the alterations on the length of the shock. The data suggest that the mitochondrial defect caused by shock is in the adenine nucleotide translocase and/or utilization mechanism in connection with the fault in ATPase activity.
Enhanced reactivity to visual stimuli in deaf individuals.

PURPOSE Several studies have reported faster response time to visual stimuli in profoundly deaf individuals. This result is often linked to the processing of peripheral targets, and it is assumed to occur in relation to attention orienting. We evaluated whether enhanced reactivity to visual events in profoundly deaf individuals can be explained by faster orienting of visual attention alone. METHODS We examined 11 deaf individuals and 11 hearing controls, in a simple detection task and in a shape discrimination task. While simple detection can be performed under distributed attention, shape discrimination requires orienting of spatial attention to the target. The same visual targets served for both tasks, presented at central or peripheral locations and corrected for cortical magnification. RESULTS The simple detection task revealed faster RTs in deaf than hearing controls, regardless of target location. Moreover, while hearing controls paid a cost in responding to peripheral than central targets, deaf participants performed equally well regardless of target eccentricity. In the shape discrimination task deaf never outperformed hearing controls. CONCLUSIONS These findings reveal that enhanced reactivity to visual stimuli in the deaf cannot be explained only by faster orienting of visual attention and can emerge for central as well as peripheral targets. Moreover, the persisting advantage for peripheral locations in the deaf, observed here under distributed attention, suggests that this spatially-selective effect could result from reorganised sensory processing rather than different attentional gradients.
Dielectric-Modulated Field Effect Transistors for DNA Detection: Impact of DNA Orientation

In this letter, we present a study that highlights the importance of electrostatic effects on DNA sequence orientation, and the subsequent influence on the functioning principles of nanogap embedded dielectric-modulated field effect transistor (DMFET) biosensors. We find that the orientation of DNA molecules is responsible for governing the sensitivity and dominance of charge or dielectric constant effect in nanogap embedded FET devices. Using 2-D TCAD simulations, the study not only provides a correct explanation for the observed trend of threshold voltage shifts for DNA detection using n-channel DMFET, which has been loosely attributed to the dominance of the charge effect, but also gives insight into the reason of higher sensitivity of p-channel over n-channel DMFET biosensors.
Identification and Characterization of E2F7, a Novel Mammalian E2F Family Member Capable of Blocking Cellular Proliferation*

The mammalian E2F family of transcription factors plays a crucial role in the regulation of cellular proliferation, apoptosis, and differentiation. Consistent with its biological role in a number of important cellular processes, E2F regulates the expression of genes involved in cell cycle, DNA replication, DNA repair, and mitosis. It has proven difficult, however, to determine the specific roles played by the various known family members in these cellular processes. The work presented here now extends the complexity of this family even further by the identification of a novel E2F family member, which we now term E2F7. Like the expression of the known E2F activators, E2F1, E2F2, and E2F3, the expression of E2F7 is growth-regulated, at least in part, through E2F binding elements on its promoter, and its protein product is localized to the nucleus and associates with DNA E2F recognition sites with high affinity. A number of salient features, however, make this member unique among the E2F family. First, the E2F7 gene encodes a protein that possesses two distinct DNA-binding domains and that lacks a dimerization domain as well as a transcriptional activation and a retinoblastoma-binding domain. In contrast to the E2F activators, E2F7 can block the E2F-dependent activation of a subset of E2F target genes as well as mitigate cellular proliferation of mouse embryo fibroblasts. These findings identify E2F7 as a novel member of the mammalian E2F transcription factor family that has properties of a transcriptional repressor capable of negatively influencing cellular proliferation.
Altered regulation of the 5‐HT system in the brain of MAO‐A knock‐out mice

Genetic deficiency of monoamine oxidase‐A (MAO‐A) induces major alterations of mood and behaviour in human. Because serotonin (5‐HT) is involved in mood regulation, and MAO‐A is responsible for the catabolism of 5‐HT, we investigated 5‐HT mechanisms in knock‐out mice (2‐month‐old) lacking MAO‐A, using microdialysis, electrophysiological, autoradiographic and molecular biology approaches. Compared to paired wild‐type mice, basal extracellular 5‐HT levels were increased in ventral hippocampus (+202%), frontal cortex (+96%) and dorsal raphe nucleus (DRN, +147%) of MAO‐A mutant mice. Conversely, spontaneous firing rate of 5‐HT neurons in the DRN (recorded under chloral hydrate anaesthesia) was ∼40% lower in mutants. Acute 5‐HT reuptake blockade by citalopram (0.2 and 0.8 mg/kg i.v.) produced a much larger increase in extracellular 5‐HT levels (by ∼4 fold) and decrease in DRN neuronal firing (with a ∼4.5 fold decrease in the drug's ED50) in MAO‐A knock‐out mice, which expressed lower levels of the 5‐HT transporter throughout the brain (−13 to −34% compared to wild‐type levels). The potency of the 5‐HT1A agonist 8‐OH‐DPAT to produce hypothermia and to reduce the firing of DRN serotoninergic neurons was significantly less in the mutants, indicating a desensitization of 5‐HT1A autoreceptors. This was associated with a decreased autoradiographic labelling of these receptors (−27%) in the DRN. Altogether, these data indicate that, in MAO‐A knock‐out mice, the enhancement of extracellular 5‐HT levels induces a down‐regulation of the 5‐HT transporter, and a desensitization of 5‐HT1A autoreceptors which allows the maintenance of tonic activity of 5‐HT neurons in the DRN.
Correlation between Radiologic and Clinical Findings in Charnley Total Hip Replacement

The main purpose of this study was to evaluate the relationship between the radiologic findings in clinically successful Charnley total hip replacements (THR) at an average of five years postoperatively (‘5-year follow-up’) and the clinical result 10 to 14 years after operation (‘10-year follow-up’). The study included 150 arthroplasties graded as clinically successful at the 5-year follow-up despite radiologic loosening of the femoral component in 41 per cent and of the acetabular component in 7 per cent. The incidence of clinical failure between the two follow-ups was 7 per cent (10 hips). Only 2 per cent (3/125) of THRs with intact components or a loose stem with migration not exceeding 4 mm became failures. Clinical failures resulted in 28 per cent (7/25) of THRs with more extensive loosening of the stem or with a loose socket. At the 10-year follow-up 47 per cent of the femoral and 13 per cent of the acetabular components were loose. Progression of loosening of the femoral stem occurred in 63 per cent and of the socket in 73 per cent between the two follow-ups. The incidence of loosening of the stem showed a significant correlation both with the extent of cementation distal to the tip and with the orientation of the prosthesis in the sagittal plane.
[Sensitivity to antibiotics of bacteria from nosocomial infections. Evolution in resuscitation services of military hospitals].

OBJECTIVE The aim of this study, conducted in the French Military hospitals, was to monitor the course of the antimicrobial sensibility of bacteria isolated from nosocomial infection in intensive care units. PATIENTS AND METHODS A prospective study has been conducted from January to December 1998 in all the intensive care units of the French Army. All the non-repetitive strains isolated from nosocomial infection were collected and sent to a reference centre. Antimicrobial susceptibility was determined by the agar dilution method. Beta-lactamase were identified by iso-electro-focalisation. Antibiotics choice and interpretative criteria were those of the "Comité Français de l'Antibiogramme de la Société Française de Microbiologie". RESULTS A total of 849 strains are included in this study. Pseudomonas aeruginosa was the most frequently isolated bacterium (20%) followed by Escherichia coli (19%) Staphylococcus aureus (15%), coagulase-negative Staphylococci (CoNS) (11%) and Enterococci (7%). Imipenem was the most effective antibiotic against enterobacteriaceae (336 isolates; 100% susceptibility). Gentamicin (92%), amikacin (92%) third generation cephalosporins (83%), aztreonam (83%) and ciprofloxacin (78%) were also very effective. Resistance to III generation cephalosporins was correlated with an extended spectrum beta-lactamase (BLSE) in 36% of cases. This BLSE could be associated with an over production of the constitutive cephalosporinase. The most frequent species producing BLSE were Enterobacter aerogenes (75% of BLSE) and Klebsiella pneumoniae (17%). Among the 172 P. aeruginosa isolated, antimicrobial susceptibility were respectively: 71% for imipenem, 62%: tobramycin, 60%: amikacin 59%: ciprofloxacin 59% piperacillin + tazobactam, 55% piperacillin, 53%: ceftazidime and 44% for ticarcillin. Seventy per cent of the 96 CoNS and 50.2% of the 126 S. aureus isolated were resistant to methicillin. A strain of S. aureus and 2 CoNS strains had intermediate resistance to teicoplanin. Twenty per cent of the 59 Enterococci strains isolated were resistant to aminopenicillins (10/11 strains of E. faecium), and 9% presented a high level of resistance to gentamicine. One strain of E. faecium was resistant to vancomycin. CONCLUSION The evolution of the susceptibility to antibiotics in intensive care units reflects the antibiotic pressure and level of cross-transmission. High rates of meticillin-resistance among staphylococci, of resistance to beta-lactams antibiotics among P. aeruginosa and of ciprofloxacin among Enterobacteriaceae are shown in this study. The implementation of appropriate strategies for surveillance and prevention is necessary.
Hypertransaminasemia in pediatric celiac disease patients and its prevalence as a diagnostic clue

OBJECTIVES:The aims of this study were to evaluate the following: 1) the prevalence of hypertransaminasemia (HT) in a pediatric celiac disease (CD) and its relation with clinical parameters; 2) the frequency of HT as the only manifestation of pediatric CD; and 3) the evolution of HT after a gluten free diet.METHODS:A total of 114 consecutive pediatric CD patients were studied (60% with classical and 40% with atypical forms). Antiendomisyum antibodies and anti-tissue transglutaminase antibodies were determined in patients with a clinical suspicion of CD (including unexplained chronic HT), in patients at risk, and in patients with preoperative increased ALT activity for minor surgery. CD was confirmed by duodenal biopsy. At baseline, the relationship between clinical factors and aminotransferase status was univariately and multivariately assessed. After starting a gluten free diet, patients were followed up, until serological markers cleared and serum aminotransferase normalized.RESULTS:HT occurred in 32% of patients (37 of 114) at diagnosis. HT was the only manifestation of CD in five patients (4.3%). Patients with HT were younger (2.9 ± 0.4 yr) than patients with normal aminotransferases (5.1 ± 0.5 yr) (p = 0.007). A higher percentage of patients with classical CD tend to have abnormal aminotransferases (73%; 95% CI = 65–81%) than do patients with atypical CD (27%; 95% CI = 19–35%) (p = 0.068). Logistic regression analysis showed that only younger age was significantly associated with HT (p = 0.039; OR = 0.8; 95% CI = 0.71–0.99). Aminotransferases normalized with a gluten free diet in all 35 patients who were followed-up, either before (n = 18) or at the same time (n = 17) as serological markers cleared.CONCLUSIONS:HT is a frequent finding in pediatric CD patients and, in a substantial proportion, may be the only manifestation of CD. Thus, serological markers of CD should be introduced in the first step of the diagnostic workup of liver diseases in pediatric patients.
Microvessel Density as a Surrogate Prognostic Marker in Patients with Multiple Myeloma: A Meta-Analysis

Background/Aims: Bone marrow (BM) angiogenesis is considered a hallmark of multiple myeloma (MM) development and progression, and can be quantified with the use of microvessel density (MVD). The purpose of this study is to provide a review and a meta-analysis of the current literature regarding the prognostic value of MVD in the overall survival (OS) of MM patients. Methods: MEDLINE was screened for studies evaluating the OS of MM patients with regard to their MVD count in BM trephine. The pooled hazard ratio (HR) and its associated 95% confidence interval (CI) among MM patients with a high and low MVD count was the primary end point. Secondary outcomes included odds ratios (OR) for 12-, 36-, and 60-month survival. Results: Ten eligible trials were identified for the analysis of the primary end point and 9 for the secondary end points. Pooled HR for OS was 1.85 (95% CI: 1.25-2.73, p = 0.002). The pooled OR of survival were 1.59 (95% CI: 1.02-2.46, p = 0.04) at 12 months, 2.90 (95% CI: 1.68-5.03, p = 0.0001) at 36 months, and 3.42 (95% CI: 2.41-4.85, p < 0.00001) at 60 months, in favor of the low MVD group. Conclusion: This meta-analysis provides persuasive evidence that MVD has significant impact on the clinical outcome of MM patients.
From research to practice: how OPUS treatment was accepted and implemented throughout Denmark

The early phases of psychosis have been hypothesized to constitute a critical period, a window of opportunity. At the same time, the early phases of psychosis are associated with increased risk of unwanted outcome, such as suicidal behaviour and social isolation. This was the background for the emergence of early intervention services, and in Denmark, the OPUS trial was initiated as part of that process.
Evaluation of Nucleic Acid Amplification Tests as Reference Tests for Chlamydia trachomatis Infections in Asymptomatic Men

ABSTRACT Urine ligase chain reaction (LCR) and PCR tests and urethral swab culture were compared for their abilities to detect Chlamydia trachomatis infection in 3,639 asymptomatic men by using one-, two-, and three-test reference standards. Frozen urine at four of five participating centers was also tested by a transcription-mediated amplification assay which was used as a reference test. LCR increased the yield of positive results by 27% and PCR increased the yield of positive results by 26% over the yield of positive results by culture (n = 295). LCR and PCR sensitivities were similar, ranging from 80.4 to 93.5%, depending on the reference standard. Culture sensitivity was substantially less. A multiple-test standard yielded LCR, PCR, and culture specificities of 99.6%, with or without discrepant analysis. Test performance varied among centers partly due to different interpretations of the testing protocols. The study confirms that urine LCR and PCR for the detection of C. trachomatis have substantially improved sensitivities over that of urethral swab culture for testing of asymptomatic men, enabling screening of this important target group. These tests, perhaps in combination, are also candidate reference tests for the conduct of test evaluation studies.