Miracle-dz/UniFAR-FTUs huggingface dataset:
Systems biology: Leading the revolution in ecotoxicology

The rapid development of new technologies such as transcriptomics, proteomics, and metabolomics (Omics) are changing the way ecotoxicology is practiced. The data deluge has begun with genomes of over 65 different aquatic species that are currently being sequenced, and many times that number with at least some level of transcriptome sequencing. Integrating these top‐down methodologies is an essential task in the field of systems biology. Systems biology is a biology‐based interdisciplinary field that focuses on complex interactions in biological systems, with the intent to model and discover emergent properties of the system. Recent studies demonstrate that Omics technologies provide valuable insight into ecotoxicity, both in laboratory exposures with model organisms and with animals exposed in the field. However, these approaches require a context of the whole animal and population to be relevant. Powerful approaches using reverse engineering to determine interacting networks of genes, proteins, or biochemical reactions are uncovering unique responses to toxicants. Modeling efforts in aquatic animals are evolving to interrelate the interacting networks of a system and the flow of information linking these elements. Just as is happening in medicine, systems biology approaches that allow the integration of many different scales of interaction and information are already driving a revolution in understanding the impacts of pollutants on aquatic systems. Environ. Toxicol. Chem. 2011;30:265–273. © 2010 SETAC
Adenocarcinoma of the prostate with endometrioid features. A light microscopic and immunohistochemical study of ten cases

The authors reviewed the histologic slides of 2600 prostatic carcinomas seen at Memorial Hospital from 1963 to 1983. In ten cases, resection specimens had a predominantly endometrioid appearance. Six patients had polypoid lesions in and around the verumontanum, and one had a polypoid lesion away from the verumontanum. Two patients had no mucosal lesions and one was not cystoscoped. Histologically, the tumors showed a tall pseudostratified columnar epithelium, usually with amphophilic cytoplasm. The cells were arranged either along papillae or in complexes of large acini or in single glands. In eight of the ten cases, the endometrioid carcinomas were associated with a prior or coexistent typical microacinar prostatic adenocarcinoma. In four cases, the endometrioid pattern existed in a pure form, although in two such cases with urethral tumors, the patients had histories of successfully treated microacinar adenocarcinomas of the posterior prostatic lobe. In one case, a urethral endometrioid tumor coexisted with a small posterior lobe microacinar adenocarcinoma. In five cases, both endometrioid and microacinar carcinomas were seen, including endometrioid and microacinar carcinomas found at the same site at different times (2 cases), tumors with a predominantly endometrioid, yet focally microacinar pattern (1 case), and primary tumors where lymph node metastases had different histologic features (2 cases). Of the three patients with a pure or predominantly endometrioid pattern treated with diethylstilbestrol, two had a marked clinical response. All ten endometrioid prostatic adenocarcinomas showed prostate‐specific antigen and prostate‐specific acid phosphatase immunoreactivity, in contrast to none of the control uterine endometrial carcinomas. In material spanning a 20‐year period, the authors have not seen a single prostatic tumor entirely analogous to the uterine endometrial carcinoma. Until such proof exists, prostatic carcinomas with endometrioid features are best classified and treated as variants of prostatic duct carcinomas.
Patterns of Stroke Recurrence According to Subtype of First Stroke Event: The North East Melbourne Stroke Incidence Study (NEMESIS)

Background Specific information about the nature of recurrent events that occur after each subtype of index stroke may be useful for refining preventive therapies. We aimed to determine whether stroke recurrence rates, the pattern of subtype recurrence, and prescription of secondary prevention agents differed according to initial stroke subtype. Methods Multiple overlapping sources were used to recruit all first-ever stroke patients from a geographically defined region of Melbourne, Australia over a 3-year period from 1996 to 1999. Potential stroke recurrences (fatal and nonfatal) occurring within 2 years of the initial event were identified following patient interview and follow up of death records. Subjects were classified into the different Oxfordshire groups and the type of first-ever stroke was compared with recurrent stroke events. Results One thousand, three hundred and sixteen first-ever strokes were registered during the 3-year period (mean age 74·4 years). A total of 103 first recurrent stroke events (fatal and nonfatal) occurred among those with a first-ever ischemic stroke or intracerebral hemorrhage (ICH) during the 2-year follow-up period. The recurrent stroke subtype was different to the index stroke subtype in most (78%) patients. People with partial anterior circulation infarct had the greatest proportion of recurrences (13%), with a third of these being the more severe total anterior circulation infarct subgroup. The relative risk of ICH after an index lacunar infarct (LACI) compared with an index non-LACI was 4·06 (95% CI 1·10–14·97, P=0·038). Prescription of secondary prevention agents was greater at 2 years after stroke than at hospital discharge, and was similar between ischemic stroke subtypes. Conclusion Approximately 9% of people with first-ever stroke suffered a recurrent event, despite many being prescribed secondary prevention agents. This has implications for the uptake of current preventive strategies and the development of new strategies. The possibility that ICH is greater among index LACI cases needs to be confirmed.
Adaptation to famine: A family of stationary-phase genes revealed by microarray analysis

Bacterial adaptation to nutrient limitation and increased population densities is central to survival and virulence. Surprisingly, <3% of Escherichia coli genes are known to play roles specific to the stationary phase. There is evidence that the leucine-responsive regulatory protein (Lrp) may play an important role in stationary phase, so this study used microarrays representing >98% of E. coli genes to more comprehensively identify those controlled by Lrp. The primary analysis compared isogenic Lrp+ and Lrp− strains in cells growing in steady state in glucose minimal medium, either in the presence or absence of leucine. More than 400 genes were significantly Lrp-responsive under the conditions used. Transcription of 147 genes was lower in Lrp+ than in Lrp− cells whether or not leucine was present; most of these genes were tightly coregulated under several conditions, including a burst of synthesis on transition to stationary phase. This cluster includes 56 of 115 genes already known to play roles in stationary phase. Our results suggest that the actual number of genes induced on entrance into stationary phase is closer to 200 and that Lrp affects nearly three-quarters of them, including genes involved in response to nutrient limitation, high concentrations of organic acids, and osmotic stress.
Promoting abstinence among relapsed chronic smokers: the effect of telephone support.

OBJECTIVES The present study used telephone support both to sustain abstinence and to encourage renewed quit attempts in smokers who had completed an intensive smoking cessation clinic. METHODS Subjects were hard-core smokers (n = 1083) who had attended a multisession cessation clinic. They were then assigned randomly to receive telephone support (intervention calls 3, 9, and 21 months after the targeted cessation clinic quit date) or no further intervention. RESULTS In the intervention condition, subjects who relapsed were significantly more likely to resume abstinence (that is, to recycle) than those in the comparison condition at follow-up (6 months: 17.8% vs 11.3%; 24 months: 25.7% vs 18.2%). Telephone support was not effective in preventing relapse, and overall differences in abstinence outcome were not significant. CONCLUSIONS The major hypothesis of the current study--that telephone support would enhance the resumption of abstinence--received partial support. However, there was no evidence either of an overall treatment effect or of an effect in preventing relapse. Telephone outreach may be more effective in the context of self-help or other less intensive interventions.
Fractal analysis design for distinguishing subject characteristics on motor control of neck pain patients

Literature reflects that there is considerable amount of research has been conducted concerning motor control and postural control of human body. Research findings also reveal the importance of stability and variability of movement in relation to spine, in particular. However, the evaluation method on stability and variability of spinal movement is limited on the linear methods in revealing the significance of movement. The knowledge on the nonlinearity and the dynamic features of spinal movement is still inadequate in describing the motor control and musculoskeletal characteristics.
Statins differ in their ability to block NF-kappaB activation in human blood monocytes.

OBJECTIVE The benefits of statin therapy in cardiovascular medicine are ascribed to its lipid-lowering effect as well as its anti-inflammatory properties. Whereas all statins have been shown to reduce cholesterol plasma levels, their effect on inflammatory markers has been inconsistent. Here, we show that statins differ markedly in their effectiveness in preventing activation of NF-kappaB, a transcription factor involved in the activation of immediately early genes during inflammation. METHODS Six statins (atorvastatin (Atv), cerivastatin (Cer), fluvastatin (Flu), lovastatin (Lov), pravastatin (Pra), simvastatin (Sim)) were tested for their ability to influence the induction of NF-kappaB in human monocytes (Mo) during inflammation. Mo isolated from healthy blood donors were incubated with LPS (10 microg/ml) in the presence and absence of statin (0.001-5 microM). NF-kappaB binding activity (EMSA), degradation and phosphorylation of the inhibitor protein IkappaB-alpha (Western blotting), tissue factor (TF) mRNA (rtPCR), and TF activity (clotting assay) were analyzed. RESULTS All statins inhibited LPS-induced NF-kappaB binding activity in Mo in a dose-dependent manner. The inhibitory effect was due to reduced phosphorylation and degradation of the NF-kappaB inhibitor protein IkappaB, and was primarily dependent on the absence of mevalonate. Whilst this effect appeared with all statins, there were marked differences in the degree of inhibition between the statins. Cer (45 +/- 9% inhibition, p < 0.05) was 9-fold more effective in reducing NF-kappaB activation than Flu (5 +/- 10% inhibition). The differences in the potency of statins (Cer > Atv > Sim > Pra > Lov > Flu) were also reflected at the transcriptional level and the protein level of NF-kappaB controlled tissue factor expression. CONCLUSIONS The finding that statins differ in their potency in interfering with the activation of NF-kappaB signaling in human monocytes further supports the hypothesis that some statins inhibit the inflammatory response more than others.
Are we prepped for preexposure prophylaxis (PrEP)? Provider opinions on the real-world use of PrEP in the United States and Canada.

BACKGROUND Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate and emtricitabine (Truvada) has demonstrated efficacy in placebo-controlled clinical trials involving men who have sex with men, high-risk heterosexuals, serodiscordant couples, and intravenous drug users. To assist in the real-world provision of PrEP, the Centers for Disease Control and Prevention (CDC) has released guidance documents for PrEP use. METHODS Adult infectious disease physicians were surveyed about their opinions and current practices of PrEP through the Emerging Infections Network (EIN). Geographic information systems analysis was used to map out provider responses across the United States. RESULTS Of 1175 EIN members across the country, 573 (48.8%) responded to the survey. A majority of clinicians supported PrEP but only 9% had actually provided it. Despite CDC guidance, PrEP practices were variable and clinicians reported many barriers to its real-world provision. CONCLUSIONS The majority of adult infectious disease physicians across the United States and Canada support PrEP but have vast differences of opinion and practice, despite the existence of CDC guidance documents. The success of real-world PrEP will likely require multifaceted programs addressing barriers to its provision and will be assisted with the development of comprehensive guidelines for real-world PrEP.
Recognition and Therapeutic Management of Migraine in 2004, in France: Results of FRAMIG 3, a French Nationwide Population‐Based Survey

Objective. —To evaluate the proportion of migraineurs who are self‐aware of their disease in France, to determine the factors (disability, quality of life, psychiatric comorbidities, and medical consultation) that may promote self‐awareness of migraine, and to assess the influence of these factors on migraine attacks.
A Multidisciplinary, Comprehensive, Ambulatory Treatment Scheme for Diabetes Mellitus in Children

A study has been carried out on 262 children with juvenile diabetes and their parents, treated up to 10 yr on an ambulatory basis by a multidisciplinary team composed of pediatric endocrinologist, nurse, dietitian, psychologist, and social worker. Comparison of the findings with those of a study performed before inception of the Counselling Center for Juvenile Diabetics revealed the following positive influences: the degree of control attained was both higher and sustained with greater regularity; there were fewer complications with no episodes of coma, brittle diabetes, or severe ketoacidosis and almost no need for hospitalization; the attitude of the affected child, his parents, and his teachers was found to be considerably improved; there was better understanding of the nature of the disease and its requirements; the child's motivation to maintain the diabetic regimen was greater and conflicts within the family circle were markedly reduced; the child's self-concept was much higher; and both scholastic achievements and social adjustment were greater. We concluded that psychological stability is a basic factor in the control of diabetes, and the value of the multidisciplinary approach in the treatment of this chronic disease is indicated.
Biological inspired secure autonomous routing mechanism for wireless sensor networks

The field of wireless sensor network (WSN) is an important and challenging research area today. Advancements in sensor networks enable a wide range of environmental monitoring applications. Multihop routing in WSN is affected by new nodes constantly entering/leaving. Moreover, secure routing is a difficult problem due to the resource limitations in WSN. Thus, biological inspired algorithms are reviewed and enhanced to tackle the problems. Ant routing and human security system have shown excellent performance. Certain parameters as energy level, velocity, packet reception, dropping, mismatch rates and packet sending power are considered while making decision. The decision will come up with the optimal route and also to take best action against security attacks. In this paper, the design and initial work of BIOlogical Inspired Secure Autonomous Routing Protocol (BIOSARP) is presented. The proposed bio-inspired mechanism will meet the enhanced WSN requirements, including better delivery ratio, less energy consumption and routing overhead.
Decreased immunoreactivity of the polypeptide precursor pro-opiomelanocortin (POMC) and the prohormone convertase pc1/3 after chronic ethanol exposure in Sprague-Dawley rats.

BACKGROUND The melanocortin (MC) peptides and opioid peptide β-endorphin are cleaved from the polypeptide precursor pro-opiomelanocortin (POMC). POMC-derived peptides are generated by extensive posttranslational processing that involves several enzymes including prohormone convertase 1/3 and 2 (PC1/3 and PC2). Because ethanol (EtOH) decreases POMC mRNA levels, we determined whether the exposure to an EtOH-containing diet (ED) would significantly reduce central immunoreactivity (IR) of POMC, PC1/3, PC2, and β-endorphin. METHODS Male Sprague-Dawley rats were given 18 days of access to a normal rodent chow or a control diet (CD), or short-term (4 days) or long-term (18 days) access to an ED. At the end of the study, rats were perfused with 4% paraformaldehyde, and their brains were sectioned into sets for processing with POMC, PC1/3, PC2, and β-endorphin IR. RESULTS Rats exposed to an ED for 18 days (ED18) exhibited significant reductions of POMC and PC1/3 IR in the arcuate nucleus of the hypothalamus (Arc) relative to rats pair-fed a CD. On the other hand, rats exposed to an ED did not show any changes of central β-endorphin or PC2 IR relative to rats pair-fed a CD, regardless of length of exposure. Because there were no differences in body weights or caloric intake between the CD and ED groups, reductions of POMC and PC1/3 IR in ED-treated rats are best explained by EtOH exposure rather than altered energy balance. CONCLUSIONS This study shows that EtOH site-specifically reduces POMC and PC1/3 IR in rat brain. These observations are consistent with EtOH-induced reductions of α-melanocyte-stimulating hormone (α-MSH) and POMC IR that were previously reported. As MC agonists have been shown to blunt EtOH intake in rodents, exogenous MC receptor agonists, as well as targets that may increase the synthesis of endogenous α-MSH (e.g., PC1/3), may have therapeutic value for treating alcohol abuse disorders and alcoholism.
Just-in-time Database-Driven Web Applications

'Just-in-time' database-driven web applications (DBWA) are inexpensive, quickly developed software that can be put to many uses within a healthcare organization. DBWA garnered 73,873 hits on our system-wide intranet in 2002. They enabled collaboration and communication via user-friendly web browser-based interfaces for both mission and patient care critical functions. Nineteen DBWA were developed The application categories that comprised 80 per cent of the hits were results reporting (27%), graduate medical education (26%), research (20%), and bed availability (8%). The mean number of hits per application was 3,888 (SD 5598; range 14-19,879). A model is described for 'just-in-time' DBWA development.
Transcriptional and DNA Binding Activity of the Foxp1/2/4 Family Is Modulated by Heterotypic and Homotypic Protein Interactions

ABSTRACT Foxp1, Foxp2, and Foxp4 are large multidomain transcriptional regulators belonging to the family of winged-helix DNA binding proteins known as the Fox family. Foxp1 and Foxp2 have been shown to act as transcriptional repressors, while regulatory activity of the recently identified Foxp4 has not been determined. Given the importance of this Fox gene subfamily in neural and lung development, we sought to elucidate the mechanisms by which Foxp1, Foxp2, and Foxp4 repress gene transcription. We show that like Foxp1 and Foxp2, Foxp4 represses transcription. Analysis of the N-terminal repression domain in Foxp1, Foxp2, and Foxp4 shows that this region contains two separate and distinct repression subdomains that are highly homologous termed subdomain 1 and subdomain 2. However, subdomain 2 is not functional in Foxp4. Screening for proteins that interact with subdomains 1 and 2 of Foxp2 using yeast two-hybrid analysis revealed that subdomain 2 binds to C-terminal binding protein 1, which can synergistically repress transcription with Foxp1 and Foxp2, but not Foxp4. Subdomain 1 contains a highly conserved leucine zipper similar to that found in N-myc and confers homo- and heterodimerization to the Foxp1/2/4 family members. These interactions are dependent on the conserved leucine zipper motif. Finally, we show that the integrity of this subdomain is essential for DNA binding, making Foxp1, Foxp2, and Foxp4 the first Fox proteins that require dimerization for DNA binding. These data reveal a complex regulatory mechanism underlying Foxp1, Foxp2, and Foxp4 activity, demonstrating that Foxp1, Foxp2, and Foxp4 are the first Fox proteins reported whose activity is regulated by homo- and heterodimerization.
Detection of Acute Tolerance to the Analgesic and Nonanalgesic Effects of Remifentanil Infusion in a Rabbit Model

Although acute tolerance to analgesia develops rapidly with remifentanil, it is unknown whether acute tolerance also develops to its nonanalgesic effects. We investigated the analgesic and cardiorespiratory effects of remifentanil during a continuous infusion in a rabbit model. Ten tracheotomized New Zealand White rabbits with arterial and venous accesses were placed on a sling that allowed for reasonably free movement. In spontaneously breathing conscious animals, remifentanil was infused IV at a constant-rate of 0.3 &mgr;g · kg−1 · min−1 for 360 min. Sedative/analgesic and cardiorespiratory variables were assessed repeatedly during remifentanil infusion, including the number of animals behaviorally unresponsive to clamping the forepaw (nonresponders) and subcutaneous electrical stimulation thresholds required to elicit head lift (HLT: pain detection/arousal threshold) and escape movement responses (EMT: pain tolerance threshold). Within 60–120 min of starting the infusion, the number of nonresponders, HLT, EMT, and Paco2 increased significantly, whereas blood pressure, heart rate, and respiratory rate decreased. Thereafter, all variables returned towards preinfusion levels despite continuing infusion. These results indicate that during a remifentanil infusion acute tolerance develops for both its analgesic and cardiorespiratory effects.
Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

OBJECTIVE Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). PATIENTS AND METHODS We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary β2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. RESULTS The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine β2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for β2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. CONCLUSIONS NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.