Miracle-dz/UniFAR-FTUs huggingface dataset:
Systemic Endothelial Cell Markers in Primary Antiphospholipid Syndrome

Summary The pathogenic mechanism underlying the prothrombotic tendency of Hughes’ or antiphospholipid syndrome (APS) has not been elucidated. Numerous procoagulant mechanisms have been tested including platelet activation, monocyte tissue factor (TF) expression and endothelial cell (EC) activation. There is some evidence for the latter from studies on cultured human umbilical vein endothelial cells (HUVEC). Incubation with antiphospholipid antibodies (aPL) induces EC activation in vitro. We investigated whether there was evidence of EC perturbation in vivo using enzyme-linked immunosorbant assays (ELISAs) for soluble markers of EC dysfunction. Serum and plasma were collected from controls and patients with primary APS and ELISAs performed to quantify soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), endothelin-1 (ET-1), von Willebrand factor (vWF) and soluble tissue factor (sTF). In addition, soluble p-selectin (p-selectin) and vascular endothelial growth factor (VEGF) were measured: the former as a marker of platelet activation, the latter as a potential mediator of TF expression. No significant differences in the levels of blood-borne soluble markers were detected between the patient and control groups except for VEGF and sTF, patients having significantly higher levels of VEGF and sTF than controls (p <0.05). These results suggest plasma soluble tissue factor and VEGF may play a role in the pathogenesis of thrombosis in APS, although the cell of origin of these molecules remains unclear.
Antidepressant drug development: Focus on triple monoamine reuptake inhibition

Many patients with major depressive disorder (MDD) only partially respond, and some have no clinically meaningful response, to current widely used antidepressant drugs. Due to the purported role of dopamine in the pathophysiology of depression, triple-reuptake inhibitors (TRIs) that simultaneously inhibit serotonin (5-HT), norepinephrine (NE) and dopamine reuptake could be a useful addition to the armamentarium of treatments for MDD. A TRI should more effectively activate mesolimbic dopamine-related reward-networks, restore positive mood and reduce potent 5-HT reuptake blockade associated “hypodopaminergic” adverse effects of decreased libido, weight gain and “blunting” of emotions. On the other hand, dopaminergic effects raise concern over abuse liability and TRIs may have many of the cardiovascular effects associated with NET inhibition. Several clinical development programs for potential TRI antidepressants have failed to demonstrate significantly greater efficacy than placebo or standard of care. Successful late-stage clinical development of a TRI is more likely if experimental research studies in the target population of depressed patients have demonstrated target engagement that differentially and dose-dependently improves assessments of reward-network dysfunction relative to existing antidepressants. TRI treatment could be individualized on the basis of predictive markers such as the burden of decreased positive mood symptoms and/or neuroimaging evidence of reward network dysfunction. This review focuses on how the next generation of monoamine-based treatments could be efficiently developed to address unmet medical need in MDD.
Intragenomic heterogeneity in the 16S rRNA genes of Flavobacterium columnare and standard protocol for genomovar assignment.

Genetic variability in 16S rRNA gene sequences has been demonstrated among isolates of Flavobacterium columnare, and a restriction fragment length polymorphism (RFLP) assay is available for genetic typing of this important fish pathogen. Interpretation of restriction patterns can be difficult due to the lack of a formal description of the expected number and sizes of DNA fragments generated for each of the described genomovars. In this study, partial 16S rRNA gene sequences (ca. 1250-bp fragment) from isolates representing each described genomovar and isolates generating unique restriction patterns were cloned and sequenced. The results demonstrated that some isolates contained up to three different 16S rRNA genes whose sequences generate different RFLP patterns due to intragenomic heterogeneity within HaeIII restriction sites. The occurrence of HaeIII restriction sites within the portion of the 16S rRNA gene used for typing the F. columnare isolates and intragenomic heterogeneity within these sites explained the restriction patterns observed following RFLP analyses. This research provides a standard protocol for typing isolates of F. columnare by RFLP and a formal description of the expected restriction patterns for the previously described genomovars I, II, II-B and III. Additionally, we describe a new genomovar, I/II.
Histological and ultrastructural findings suggesting an initiating role for Chlamydia pneumoniae in the pathogenesis of atherosclerosis.

AIMS: An association between Chlamydia pneumoniae and atherosclerosis is now well established. The finding of C. pneumoniae in atherosclerotic lesions has led to the hypothesis that this organism may have an aetiological role in atherogenesis. The implications of such a concept are enormous, but to date the pathological features of the lesion have not been examined in the light of this new hypothesis. This study was designed to determine the pathological basis of the association between C.pneumoniae and atherosclerotic lesions. METHODS: The pathological features of 50 atherosclerotic lesions from 50 different patients, in which C.pneumoniae had been demonstrated by immunocytochemistry and PCR techniques, were examined using light and electron microscopy techniques. In 20 cases the lesions were fatty streaks, 20 were fibro-atheroma lesions, and 10 were advanced, complicated lesions. RESULTS: Intimal smooth-muscle cells infected with C. pneumoniae exhibit vacuolation, loss of myofilaments, an increase in lipid, rupture and fragmentation. Macrophages phagocytose these muscle cell fragments, lipid and C. pneumoniae. Large numbers of extracellular C. pneumoniae organisms were identified in the central necrotic core, in areas of fibrosis, in areas of fragmentation of the internal elastic lamina, and in ceroid bodies. Neither pathological changes nor organisms were seen in the endothelium. CONCLUSIONS : C. pneumoniae infection of intimal smooth&hypen; muscle cells is accompanied by cytoplasmic alterations and damage. The fatty streak appears to be formed by a macrophage response to this muscle damage. C. pneumoniae is found in early, mature and advanced lesions. This is the first study of the pathology of atherosclerosis suggesting that the lesion be interpreted as an infective chlamydial granuloma.
Chronic pain care

Objective Experiencing pain not only affects patients’ biopsychosocial functioning but also the existential domain. Attention to the existential, in addition to the biopsychosocial domains, might thus be important in chronic pain care. Therefore, we investigated: (a) how satisfied patients were with the attention of their practitioners to the impact of pain on biological, psychological, social, and existential life domains, and (b) how satisfaction with each domain was related to patient functioning. Method Pain patients (N = 163) were questioned on their satisfaction with the attention of their practitioners to biological, psychological, social, and existential life domains, and on pain intensity, pain disability, life satisfaction, and depressive symptoms. Results Patients reported low satisfaction with the attention of their practitioners to the social and existential domains. Satisfaction with each domain was negatively related with pain intensity, pain disability, and depressive symptoms and positively related with life satisfaction. Only satisfaction with the existential domain was able to predict all functional outcomes above and beyond all other satisfaction variables modeled simultaneously. Conclusions Patients reported not feeling satisfied with the attention to the social and existential life domains. Furthermore, practitioners’ attention to the existential domain seems highly important for patient functioning. Openness to existential concerns of pain patients might thus be an important aspect of chronic pain care.
Trends in rates of mental illness in homicide perpetrators

Background The rise in homicides by those with serious mental illness is of concern, although this increase may not be continuing. Aims To examine rates of mental illness among homicide perpetrators. Method A national consecutive case series of homicide perpetrators in England and Wales from 1997 to 2006. Rates of mental disorder were based on data from psychiatric reports, contact with psychiatric services, diminished responsibility verdict and hospital disposal. Results Of the 5884 homicides notified to the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness between 1997 and 2006, the number of homicide perpetrators with schizophrenia increased at a rate of 4% per year, those with psychotic symptoms at the time of the offence increased by 6% per year. The number of verdicts of diminished responsibility decreased but no change was found in the number of perpetrators receiving a hospital order disposal. The likeliest explanation for the rise in homicide by people with psychosis is the misuse of drugs and/or alcohol, which our data show increased at a similar magnitude to homicides by those with psychotic symptoms. However, we are unable to demonstrate a causal association. Although the Poisson regression provides evidence of an upward trend in homicide by people with serious mental illness between 1997 and 2006, the number of homicides fell in the final 2 years of data collection, so these findings should be treated with caution. Conclusions There appears to be a concomitant increase in drug misuse over the period, which may account for this rise in homicide. However, an increase in the number of people in contact with mental health services may suggest that access to mental health services is improving. Previous studies have used court verdicts such as diminished responsibility as a proxy measure of mental disorder. Our data indicate that this does not reflect accurately the prevalence of mental disorder in this population.
Chorioamnionitis and neonatal outcome in preterm infants: a clinical overview

Abstract The term chorioamnionitis is used to refer to an intrauterine infection/inflammation occurring between the maternal tissues and the fetal membranes (choriodecidual space) or in the fetal annexes (chorioamniotic membranes, amniotic fluid, umbilical cord). Histological examination of the placenta is the gold standard for diagnosis. However, clinical, biochemical and microbiological criteria are also used to define the disease. The literature contains a large body of evidence showing that chorioamnionitis is the leading cause of very preterm birth and, therefore, contributes significantly to neonatal morbidity and mortality. In recent decades, numerous studies have attempted to establish whether, and to what extent, intrauterine infection/inflammation might negatively affect the short- and long-term outcome of preterm infants. The question is still unanswered. The discrepancy observed across studies can be attributed largely to the use of different inclusion and exclusion criteria, diagnostic criteria and methods, and to whether or not potential confounding factors, such as gestational age were considered. Anyhow, the association between chorioamnionitis and severe prematurity requires serious efforts by researchers to clarify the mechanisms linking intrauterine infection/inflammation with preterm birth, and thus to identify strategies that may guide clinicians’ diagnostic and therapeutic choices, with regard to both mothers and infants.
Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies.

OBJECTIVE There is strong evidence for a genetic contribution to schizophrenia, but efforts to identify susceptibility genes have been largely unsuccessful because of the low power of individual studies. The authors' goal was to evaluate the collective evidence for an association between the Val158/108Met polymorphism of the catechol O-methyltransferase (COMT) gene and schizophrenia. METHOD They performed separate meta-analyses of existing case-control and family-based association studies. RESULTS Overall, case-control studies showed no indication of an association between either allele and schizophrenia, and family-based studies found modest evidence implicating the Val allele in schizophrenia risk. The pooled analyses of studies from diverse geographical regions may have obscured ethnic differences in patterns of genetic risk for schizophrenia. Stratification of the studies by ethnicity of the subjects yielded evidence for an association with the Val allele in case-control studies of European samples and, especially, in family-based studies of European samples. Case-control and family-based studies of Asian samples produced mixed results and, overall, little evidence for association. CONCLUSIONS The results of the two types of association studies diverged somewhat, but the evidence from the family-based studies, although based on fewer reports, may be more accurate. The Val allele may be a small but reliable risk factor for schizophrenia for people of European ancestry, but the influence of this polymorphism on risk in Asian populations remains unclear. These results call for more family-based studies to confirm the association between COMT and schizophrenia in European samples and to clarify its contribution to risk in Asian samples. They also suggest that case-control studies should use methods of genomic control to avoid being confounded by population stratification.
Epilepsies of neonatal onset: seizure type and evolution

Most neonatal seizures are occasional seizures and not true epilepsy. This study investigates seizure types of true neonatal epilepsies and their evolution with development. Seventy‐five children with epilepsies of onset within 1 month of life, who were examined between 1970 and 1995, and whose seizure types could be confirmed with ictal EEG recordings, were studied. The patients were followed up for a minimum of 3 years and the evolution of epileptic syndromes was investigated. Sixty‐three (84%) of 75 patients had partial seizures, while nine had generalized seizures, and only three had both generalized and partial seizures. Twenty‐three of 24 neonates with benign familial or non‐familial neonatal convulsions presented with partial seizures; these syndromes should not necessarily be categorized into generalized epilepsy as they are in the present International Classification. Age‐dependent changes were a common feature of symptomatic neonatal epilepsies. Eighteen (41%) of 44 patients with symptomatic epilepsies of neonatal onset developed West syndrome in infancy. Fifteen (83%) of these 18 patients presented with symptomatic localization‐related epilepsy in the neonatal period. In seven of these 15 patients, West syndrome was followed by localization‐related epilepsy. Symptomatic localization‐related epilepsy with transient West syndrome in infancy is another type of age‐dependent epileptic syndrome.
Health-related quality of life in women with metastatic breast cancer treated with trastuzumab (Herceptin).

The measurement of health-related quality of life (HRQL) was an important component of clinical trials of trastuzumab (Herceptin; Genentech, San Francisco, CA) in women with progressive HER2-overexpressing metastatic breast cancer who may or may not have had prior chemotherapy. Health-related quality of life was measured at baseline and specified intervals during therapy using the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire (QLQ-C30, version 1.0). Five domains were chosen a priori for analysis: global quality of life, physical, role and social functioning, and fatigue. In the phase II study, in which trastuzumab was given alone, there was no change in on-treatment QLQ-C30 scores compared with baseline. These results suggest that trastuzumab does not adversely affect HRQL during therapy. In the phase III study, the effects of trastuzumab plus chemotherapy were compared with those of chemotherapy alone. A comparison of QLQ-C30 scores during treatment did not show statistically significant differences between the two groups at the preset level of P = . 01. However, comparison of on-treatment scores with baseline in patients receiving chemotherapy alone indicated mild worsening of physical and role functioning and of fatigue throughout the duration of treatment, whereas a similar comparison of those receiving chemotherapy with trastuzumab revealed mild worsening of role functioning at weeks 8 and 20 and of fatigue only at week 8. These results suggest that trastuzumab may be associated with an amelioration of the deleterious effects of chemotherapy alone. In summary, in the doses and schedules used in these studies, trastuzumab is not associated with worsening of HRQL.
Management of blunt major pancreatic injury.

BACKGROUND Major duct injury is the principal determinant of outcome for patients with pancreatic trauma, and there are a number of therapeutic choices available specific to the location of the insult. We report a series of blunt major pancreatic injury cases, with a review of the different procedures used and a discussion of the results. METHODS A total of 48 cases of blunt major pancreatic injury treated during a 10-year period at one trauma center were reviewed retrospectively. Diagnosis and assessment of injury severity were based on imaging studies and proved by surgical findings. Charts were reviewed to establish the mechanism of injury, surgical indications and imaging studies, management strategy, and outcome. RESULTS Of the 32 grade III patients, 19 underwent distal pancreatectomy with splenectomy, 8 had pancreatectomy with preservation of the spleen, and 2 received a pancreatic duct stent, with the remaining 3 individuals undergoing nonsurgical treatment, pancreaticojejunostomy, and drainage alone, respectively. The grade III complication rate was 60.6%. Of the 14 grade IV patients, 4 underwent drainage alone because of the severity of the associated injuries, 4 underwent pancreaticojejunostomy, 3 had distal pancreatectomy with splenectomy, and 1 underwent distal pancreatectomy. The two remaining patients received a pancreatic duct stent. The grade IV complication rate was 53.8%. The Whipple procedure was performed for two grade V patients; one died subsequently. For all 48 patients, intraabdominal abscess was the most common morbidity (n = 11) followed, in order of prevalence, by major duct stricture (n = 4), pancreatitis (n = 2), pseudocyst (n = 2), pancreatic fistula (n = 1), and biliary fistula (n = 1). All stented cases developed complications, with one dying and three experiencing major duct stricture. CONCLUSION The complication rate for our cases of blunt major pancreatic injury was high (62.2%), especially when treatment was delayed more than 24 hours; the same result was also noted for cases transferred from other institutions. Distal pancreatectomy with spleen preservation had a lower complication rate (22.2%) compared with other procedures and is suggested for grade III and grade IV injuries. Magnetic resonance pancreatography was unreliable early after injury but was effective in the chronic stage. Although pancreatic duct stenting can be used to treat posttraumatic pancreatic fistula and pseudocyst, the major duct stricture in the chronic stage of recovery and the risk of sepsis in the acute stage must be overcome.
Knowing the Enemy: Western Understanding of Islam at the Time of the Crusades

In 1076, some twenty years before the First Crusade was launched, Pope Gregory VII wrote to al-Nāşir, Sultan of Bougie in what is now Algeria: For there is nothing which Almighty God, who wishes that all men should be saved and that no man should perish, more approves in our conduct, than that a man should first love God and then his fellow men … Most certainly you and we ought to love each other in this way more than other races of men, because we believe and confess one God, albeit in different ways, whom each day we praise and reverence as the creator of all ages and the governor of this world. For, as the Apostle says: “He is our peace, who hath made both one”. This enlightened view of Islam was not widely shared in Latin Christendom at that time, nor was it rooted in any very profound knowledge of the Muslim religion. B. Z. Kedar is, I think, correct in his view that a good deal of information about Islam was available in the West before the crusades, both in written and oral sources, but because there was a general lack of interest in the subject, no attempt had been made to coordinate this knowledge.
Photobleaching of Fluorescent Dyes under Conditions Used for Single-Molecule Detection:  Evidence of Two-Step Photolysis.

The photostability of fluorescent dyes is of crucial importance for the statistical accuracy of single-molecule detection (SMD) and for the image quality of scanning confocal microscopy. Concurrent results for the photostability were obtained by two different experimental techniques. First, the photostabilities of several coumarin and rhodamine derivatives in aqueous solution were obtained by monitoring the steady-state fluorescence decay in a quartz cell. Furthermore, an epi-illuminated microscope, continuous wave (CW) excitation at 514.5 nm, and fluorescence correlation spectroscopy (FCS) with a newly developed theory were used to study the photobleaching characteristics of rhodamines under conditions used for SMD. Depending on the rhodamine structure, the probability of photobleaching, p(b), is in the order of 10(-)(6)-10(-)(7) for irradiances below 10(3) W/cm(2). However, a considerable increase of p(b) for irradiances above this level was observed which can only be described by photobleaching reactions from higher excited states (two-step photolysis). In view of these observations, the probability of photobleaching, p(b), as well as a closed expression of its dependence on the CW excitation irradiance considering a five-level molecular electronic state model with the possibility of photobleaching from higher excited electronic states, is derived. From this model, optimal conditions for SMD with respect to the number of emitted fluorescence photons and to the signal-to-background ratio are discussed, taking into account both saturation and photobleaching. The additional photobleaching due to two-step photolysis limits the applicable irradiance.
Prior Transient Ischemic Attack and Dementia After Subsequent Ischemic Stroke

Although functional recovery and survival after ischemic stroke seem to improve in patients with prior transient ischemic attack (TIA), little is known about the effect of prior TIA on poststroke cognition. To evaluate the impact of prior TIA on dementia, 1697 nonaphasic patients who survived the first month after their first-ever ischemic stroke were identified from the population-based registry of Dijon, France, from 1985 to 2007 and divided into 3 groups according to the time interval between prior TIA and stroke (<4 wk, ≥4 wk, no TIA). Outcome was dementia diagnosed by neurologists using Diagnostic and Statistical Manual of mental disorders-III or IV criteria over the first month after stroke. Multivariate analyses were performed using logistic regression models. The prevalence of dementia after stroke was 20.6% [95% confidence interval (CI), 18.5-22.7], 26.8% (95% CI, 13.3-40.4), and 33.1% (95% CI, 27.3-38.9) among patients without TIA, with a prestroke TIA≥4 weeks, and with a prestroke TIA<4 weeks, respectively. Patients with prestroke TIA<4 weeks (adjusted odds ratio: 1.83; 95% CI, 1.32-2.52; P=0.0003) had a higher risk of dementia than those without TIA.