Miracle-dz/UniFAR-FTUs huggingface dataset:
Retinoblastoma as an Epigenetic Disease: A Proposal

The aim of the present review is to give new insights into the pathogenesis of retinoblastoma, by applying the principles of Epigenetics to the analysis of clinical, epidemiological, and biological data concerning the disease. As an emerging new scientific approach linking the genome to the environment, Epigenetics, as applied to the interpretation of clinical, epidemiological and biological data in retinoblastoma, can not only explain the inconsistencies of the mutational (“two hit”) model, but also open new outstanding scenarios in the fields of diagnosis, treatment and prevention of this eye tumour. This review is both a collection of literature data arguing against the role of the mutational (“two hit”) model in the genesis of retinoblastoma, and a documented evaluation of how the Epigenetic, rather than the genetic model fit the variegated phenotypic expression of the disease. The epigenetic model in the genesis of retinoblastoma, proposed herein, emphasizes the role of environment and the interaction of the environment with the genome, in generating reti-noblastoma in young children. Environmental toxicants, including radiations, wrong diets, and infectious diseases, among others, all play a major role in conditioning the degree of DNA methylation in embryos and foetuses during pregnancy, thus leading to stable, functional alterations of the genome, which, on the other hand, can be also transmit-ted from generation to generation, thus mimicking a hereditary disease. An accurate analysis of the currently available literature on both retinoblastoma and Epigenetics, coupled with the knowledge of the variegated phenotypic expression of the disease, can easily lead to the conclusion that retinoblastoma is an epigenetic, rather than a genetic disease.
Caregiver burden among dementia patient caregivers: A review of the literature

PurposeTo identify current evidence of factors influencing dementia-related caregiver burden (CB), describe patient and caregiver characteristics associated with CB, and describe evidence-based interventions designed to lessen the burden of caregiving. Data sourcesComprehensive literature review of Cumulative Index of Nursing and Allied Health Literature, MEDLINE, and Psych Info was performed for the years 1996–2006 of peer-reviewed journals using keywords CB and dementia. ConclusionDementia caregiving has been associated with negative effects on caregiver health and early nursing home placement for dementia patients. Many factors influence the impact of the caregiving experience such as gender, relationship to the patient, culture, and personal characteristics. Although various interventions have been developed with the goal of alleviating CB, evidence suggests that individually developed multicomponent interventions including a diversity of services will decrease burden, improve quality of life, and enable caregivers to provide at-home care for longer periods prior to institutionalization. Implications for practiceThe ability to properly assess the dementia patient–caregiver dyad related to CB is critical to decreasing its negative physical and psychological health outcomes. Appropriately tailored interventions can improve the health and well-being of both caregiver and patient.
HERSCHEL/PACS SURVEY OF PROTOPLANETARY DISKS IN TAURUS/AURIGA—OBSERVATIONS OF [O i] AND [C ii], AND FAR-INFRARED CONTINUUM

The Herschel Space Observatory was used to observe ∼120 pre-main-sequence stars in Taurus as part of the GASPS Open Time Key project. Photodetector Array Camera and Spectrometer was used to measure the continuum as well as several gas tracers such as [O i] 63 μm, [O i] 145 μm, [C ii] 158 μm, OH, H2O, and CO. The strongest line seen is [O i] at 63 μm. We find a clear correlation between the strength of the [O i] 63 μm line and the 63 μm continuum for disk sources. In outflow sources, the line emission can be up to 20 times stronger than in disk sources, suggesting that the line emission is dominated by the outflow. The tight correlation seen for disk sources suggests that the emission arises from the inner disk (<50 AU) and lower surface layers of the disk where the gas and dust are coupled. The [O i] 63 μm is fainter in transitional stars than in normal Class II disks. Simple spectral energy distribution models indicate that the dust responsible for the continuum emission is colder in these disks, leading to weaker line emission. [C ii] 158 μm emission is only detected in strong outflow sources. The observed line ratios of [O i] 63 μm to [O i] 145 μm are in the regime where we are insensitive to the gas-to-dust ratio, neither can we discriminate between shock or photodissociation region emission. We detect no Class III object in [O i] 63 μm and only three in continuum, at least one of which is a candidate debris disk.
Implication of Fetal SMN2 Expression in Type I SMA Pathogenesis: Protection or Pathological Gain of Function?

Spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron gene 1 (SMN1). The SMN2 gene, which is the highly homologous SMN1 copy that is present in all the patients, is unable to prevent the disease. Most of the SMN1 transcript is full-length, whereas a substantial proportion of the SMN2 transcript lacks exon 7 (Δ7). We characterized the developmental expression of SMN2 by comparing control and SMA fetuses. The control spinal cord revealed the highest amount of FL SMN, most of which was of SMN1 origin. When analyzing the SMA spinal cord transcripts, we detected a considerable reduction in the FL/Δ7 ratios due to a decrease in the FL and an increase in Δ7 isoform. After immunoblot and immunohistochemistry analyses, we found that the amount of SMN2 protein in the SMA spinal cord and muscle was lower than in the controls. However, the results of the expression of SMN2 in intestine, lung, adrenal gland, kidney, and eye, which are unaffected by the disease, were the same in controls and SMA samples. In these tissues, SMN2 may compensate for the absence of SMN1, whereas in SMA motor neurons, a cell-specific dysregulation of the SMN2 expression could favor the onset of the acute form of the disease.
High-Resolution Magnetoencephalographic Functional Mapping of the Cortical Network Mediating Intentional Movement

Amo C, Boyajian RA, Romine JS, Otis SM: High-resolution magnetoencephalographic functional mapping of the cortical network mediating intentional movement. Am J Phys Med Rehabil 2007;86:304–309. Magnetoencephalography (MEG) is a sensitive technique that can detect and map cortical electrophysiologic activations with high spatial (mm) and temporal (msecs) resolutions. We used 148-channel whole-head MEG to record the activation sequence for the somatosensory and motor cortical network during cued hand movements in a healthy 39-yr-old subject. The complex sequence and topography of cortical activations were superimposed onto the subject's brain magnetic resonance images. Frontal premotor and supplementary motor and cingulate areas activated well before the primary motor area and again repetitively from 200 msecs onward with activations alternating repeatedly between frontal and parietal areas. The network's very close functional integration of supplementary motor areas suggests how brain injury that is localized to these regions, but not to the primary motor area itself, can disrupt integrity of movement, and why preservation of functional integrity of some areas traditionally viewed as extramotor may be necessary for recovery from neurologic disability.
Ertapenem in critically ill patients with early-onset ventilator-associated pneumonia: pharmacokinetics with special consideration of free-drug concentration.

OBJECTIVES Most information about pharmacokinetics of antimicrobial agents is obtained from studies in healthy volunteers. However, antibiotics are therapeutically used in infected patients with very different pharmacokinetic properties compared with healthy individuals. PATIENTS AND METHODS In a single-centre, prospective, open-label study, 17 adult critically ill patients with early-onset ventilator-associated pneumonia (VAP) were treated with 1 g of ertapenem infusion once a day. Blood and urine samples were collected before and at different time-points up to 24 h after medication on day 1. Concentrations of ertapenem in plasma were determined with a validated HPLC method. Free-drug concentrations were estimated using a two-class binding site equation. RESULTS The overall clinical success rate of the assessable cases was 66.7% (12/16). Pharmacokinetic parameters of ertapenem in our critically ill patients were clearly different when compared to those reported in the literature for healthy volunteers. The enhanced V(z) (17 vs. 8 L) and CL(TOT) (43 vs. 20 mL/min) with resulting lower C(max) (90 vs. 253 mg/L) and AUC(0-infinity) (418 vs. 817 mg x h/L) values were mainly related to hypoalbuminaemia (range 9.2-25.6 g/L) in our patient population. A population pharmacokinetic analysis using the NONMEM program indicated creatinine clearance as a significant covariate for explaining the between-subject variability of ertapenem in the patient population. Estimated free plasma concentrations of ertapenem exceeded a MIC(90) of 2 mg/L only for 6 h (25%) after infusion. CONCLUSIONS For an adequate dose adjustment of highly protein-bound drugs like ertapenem, knowledge of actual albumin concentrations is necessary. A shortening of the dosage interval or continuous infusion of ertapenem should be considered to ensure optimal free concentrations in critically ill patients with severe hypoalbuminaemia and normal renal function.
Frontline Science: c‐Myc regulates P‐selectin glycoprotein ligand‐1 expression in monocytes during HIV‐1 infection

Leukocyte extravasation is a crucial feature of the normal immune response to disease and infection and is implicated in various pathologies during chronic inflammatory disease. P‐Selectin glycoprotein ligand‐1 (PSGL‐1) is critical for leukocyte extravasation; however, despite extensive study, it remains unclear how its expression is regulated, which in turn, impedes a more precise understanding of how its expression level affects transmigration. To investigate the regulation of PSGL‐1, 60 subjects, with or without HIV infection, were recruited and PSGL‐1 expression in monocytes was measured. PSGL‐1 was found to be up‐regulated on leukocytes from HIV‐infected individuals, and the physiologically relevant mediators soluble CD40 ligand (sCD40L) and glutamate were able to induce PSGL‐1 transcription in human monocytes ex vivo. HIV‐1 induced PSGL‐1 induction, and its dependence on CD40L was validated further by use of the mouse‐tropic HIV (EcoHIV) mouse model of HIV infection in C57BL/6 and CD40L knockout (KO) mice. To investigate crosstalk between the signaling cascades induced by CD40L and glutamate that lead to PSGL‐1 induction, a network‐based, discrete dynamic model was developed. The model reveals the MAPK pathway and oxidative stress as critical mediators of crosstalk between CD40L and glutamate‐induced pathways. Importantly, the model predicted induction of the c‐Myc transcription factor upon cotreatment, which was validated using transcriptomic data and pharmacologic inhibition of c‐Myc. This study suggests a novel systems serology approach for translational research and reveals a mechanism for PSGL‐1 transcriptional regulation, which might be leveraged to identify novel targets for therapeutic intervention.
The IT way of loafing on the job: cyberloafing, neutralizing and organizational justice

Summary Much attention has been devoted to how technological advancements have created a brave new workplace, revolutionzing the ways in which work is being carried out, and how employees can improve their productivity and efficiency. However, the advent of technology has also opened up new avenues and opportunities for individuals to misbehave. This study focused on cyberloafing—the act of employees using their companies’ internet access for personal purposes during work hours. Cyberloafing, thus, represents a form of production deviance. Using the theoretical frameworks offered by social exchange, organizational justice and neutralization, we examined the often-neglected dark side of the internet and the role that neutralization techniques play in facilitating this misbehavior at the workplace. Specifically, we developed a model which suggested that when individuals perceived their organizations to be distributively, procedurally and interactionally unjust, they were likely to invoke the metaphor of the ledger as a neutralization technique to legitimize their subsequent engagement in the act of cyberloafing. Data were collected with the use of an electronic questionnaire and focus group interviews from 188 working adults with access to the internet at the workplace. Results of structural equation modelling provided empirical support for all of our hypotheses. Implications of our findings for organizational internet policies are discussed. Copyright # 2002 John Wiley & Sons, Ltd.
Mapping the interaction of Snf 1 with TORC 1 in Saccharomyces cerevisiae

1 Department of Chemical and Biological Engineering, Chalmers University of Technology, Göteborg, Sweden, 2 Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, Zürich, Switzerland and 3 Faculty of Science, University of Zürich, Zürich, Switzerland * Corresponding author. Department of Chemical and Biological Engineering, Chalmers University of Technology, Kemivägen 10, Göteborg 412 96, Sweden. Tel. : þ 46 31 772 3804; Fax: þ 46 31 772 3801; E-mail: nielsenj@chalmers.se
HIV Seropositivity among Paediatric Surgical Patients at the Lagos University Teaching Hospital: What Risk to the Surgeon

Background: Although much concern has been expressed about the occupational risk posed to surgeons by the HIV pandemic infection, the paediatric age group is often seen as less likely to harbor the disease. Aim: To determine the HIV infection rate among children presenting for surgical operations at the Lagos University Teaching Hospital (LUTH), Lagos. Materials, patients and method: Blood was taken from 1000 consecutive children referred to LUTH for surgical conditions and tested for HIV sero-positivity using the Western blot method. Consenting parents of sero-positive patients were also tested. Result: Five children tested positive for HIV, giving an overall infection rate of 0.5%. Four mothers and three consenting fathers were also positive. In one child, none of the parents was positive and he was suspected to have developed the disease from a previous blood transfusion prior to presentation in LUTH. This possibly resulted from transfusion of infected blood during its window period. Conclusion: Although the HIV infection rate of 0.5% in paediatric surgical group in Lagos is low, surgeons should vigilantly apply universal precautions to prevent needle-stick injuries while the rate of HIV infection should be periodically monitored to determine the trend.
Psychiatric Hospital Nursing Staff's Experiences of Participating in Group-Based Clinical Supervision: An Interview Study

Group-based clinical supervision is commonly offered as a stress-reducing intervention in psychiatric settings, but nurses often feel ambivalent about participating. This study aimed at exploring psychiatric nurses’ experiences of participating in group-based supervision and identifying psychosocial reasons for their ambivalence. Semi-structured interviews were conducted with 22 psychiatric nurses at a Danish university hospital. The results indicated that participation in clinical supervision was difficult for the nurses because of an uncomfortable exposure to the professional community. The sense of exposure was caused by the particular interactional organisation during the sessions, which brought to light pre-existing but covert conflicts among the nurses.
Success of Meniscal Repair at Anterior Cruciate Ligament Reconstruction

Background Meniscal repair is performed in an attempt to prevent posttraumatic arthritis resulting from meniscal dysfunction after meniscal tears. The socioeconomic implications of premature arthritis are significant in the young patient population. Investigations and techniques focusing on meniscus preservation and healing are now at the forefront of orthopaedic sports medicine. Hypothesis Concomitant meniscal repair with anterior cruciate ligament reconstruction is a durable and successful procedure at 2-year follow-up. Study Design Case series; Level of evidence, 4. Methods All unilateral primary anterior cruciate ligament reconstructions entered in 2002 in a cohort who had meniscal repair at the time of anterior cruciate ligament reconstruction were evaluated. Validated patient-oriented outcome instruments were completed preoperatively and then again at the 2-year postoperative time point. Reoperation after the index procedure was also documented and confirmed by operative reports. Results A total of 437 unilateral primary anterior cruciate ligament reconstructions were performed with 82 concomitant meniscal repairs (54 medial, 28 lateral) in 80 patients during the study period. Patient follow-up was obtained on 94% (77 of 82) of the meniscal repairs, allowing confirmation of meniscal repair success (defined as no repeat arthroscopic procedure) or failure. The overall success rate for meniscal repairs was 96% (74 of 77 patients) at 2-year follow-up. Conclusion Meniscal repair is a successful procedure in conjunction with anterior cruciate ligament reconstruction. When confronted with a “repairable” meniscal tear at the time of anterior cruciate ligament reconstruction, orthopaedic surgeons can expect an estimated >90% clinical success rate at 2-year follow-up using a variety of methods as shown in our study.
Hypertension Induced in Pregnant Mice by Placental Renin and Maternal Angiotensinogen

Maternal hypertension is a common complication of pregnancy and its pathophysiology is poorly understood. This phenomenon was studied in an animal model by mating transgenic mice expressing components of the human renin-angiotensin system. When transgenic females expressing angiotensinogen were mated with transgenic males expressing renin, the pregnant females displayed a transient elevation of blood pressure in late pregnancy, due to secretion of placental human renin into the maternal circulation. Blood pressure returned to normal levels after delivery of the pups. Histopathologic examination revealed uniform enlargement of glomeruli associated with an increase in urinary protein excretion, myocardial hypertrophy, and necrosis and edema in the placenta. These mice may provide molecular insights into pregnancy-associated hypertension in humans.
Differential predation by the generalist predator Orius insidiosus on congeneric species of thrips that vary in size and behavior

We investigated interactions between the generalist predator Orius insidiosus (Say) (Heteroptera: Anthocoridae) and two species of thrips prey, Frankliniella bispinosa (Morgan) and Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), and interspecific differences in morphology and behavior between these prey species that could contribute to differences in predation by O. insidiosus. Frankliniella occidentalis is significantly larger than F. bispinosa. Frankliniella bispinosa has greater mobility compared with F. occidentalis. When O. insidiosus was offered either F. bispinosa or F. occidentalis as prey in single species trials, there were no significant differences in the number of prey captured. However, O. insidiosus had significantly more encounters with F. bispinosa than with F. occidentalis. In arenas with equal numbers of both species, O. insidiosus encountered and captured F. occidentalis more than F. bispinosa. In large arenas with two pepper plants (Capsicum annuum L.), O. insidiosus preyed on more F. occidentalis than on F. bispinosa. These results indicate that O. insidiosus can prey on both thrips species, but that it preferentially captures F. occidentalis. The greater locomotion and movement of F. bispinosa, perhaps combined with its smaller size, allow it to evade predation by O. insidiosus better than F. occidentalis. Consequently, the observed preference of O. insidiosus for F. occidentalis is not exclusively a function of active selection by the predator but also could arise from inherent differences among prey. We propose this differential predation as a mechanism contributing to observed differences in the temporal dynamics of these species in pepper fields.
Anémie en milieu hospitalier Marocain: Typologie et influences des facteurs sociodémographiques sur son incidence

EnglishAnaemia is a public health problem. Nationally, more than one third of the women and children are affected. Aim: Assess anaemia typology in an hospital setting and study the impact of socio-demographic factors on the occurrence of anaemia and make a typology using hemogram. Method: Eighty two sick (42 women and 40 men) were observed in an internal medical unit in the Idrissi hospital- Kenitra. The only inclusion criteria was anemia status (less than 10g/L Haemoglobin). Results: Level of instruction of patients varies remarkably with age, sex and area of residency. Poverty and inaccessibility to health facilities have an impact on apparition of anaemia. At the biological aspect, the microcytic anaemia is the frequent form with 39%, while the macrocytic represents 37.8% and normocytic one affects 23.2% of the subjects. According to TCMH levels, hypo chromic anaemia is found in 63.4% and normochromic in 36.6%. Severe anemia ( HB Conclusion: Anaemia is a frequent affection in this hospital setting. Its severity is associated to weakness of immunity defence and many inherent diseases. francaisAu Maroc l�anemie est un probleme de sante publique. Elle touche plus d�un tiers a l�echelle nationale chez les femmes et les enfants. Objectif: Etudier la typologie de l�anemie et influences des facteurs sociodemographiques sur son incidence en milieu hospitalier Marocain Methode: Cette etude a portee sur 82 malades (42 femmes et 40 hommes) qui ont ete observes au service de medecine interne, hopital El Idrissi de Kenitra. L�unique critere d�inclusion est la presence d�anemie (hemoglobine Resultats: Le niveau d�instruction des patients varie de facon remarquable selon l�âge, le sexe et le milieu de residence. La pauvrete et l�inaccessibilite aux services de sante sont parmi les facteurs sociodemographiques qui ont le plus d�impact sur l�apparition et le developpement de l�anemie chez la majorite des cas. Sur le plan biologique, l�anemie microcytaire est la forme la plus frequente (39%). Les anemies macrocytaires arrivent en seconde position (37,8%). Tandis que l�anemie hypochrome (63,4%) est plus rencontree par rapport a l�anemie normochrome (36,6%). Les resultats ont montre aussi que l�anemie severe (Hb Conclusion: L�anemie est une affection frequente en pratique hospitaliere courante. Sa severite est associee a la diminution de la capacite immunitaire des malades et aux multiples pathologiques inherentes.