Miracle-dz/UniFAR-FTUs huggingface dataset:
Nitric oxide‐mediated cytoprotection of hepatocytes from glucose deprivation‐induced cytotoxicity: Involvement of heme oxygenase‐1

Heme oxygenase‐1 (HO‐1) is the rate‐limiting enzyme in heme catabolism, which leads to the generation of carbon monoxide (CO), biliverdin, and free iron. One of 3 mammalian HO isoforms, HO‐1, is a stress‐responsive protein and known to modulate such cellular functions as cytokine production, cell proliferation, and apoptosis to protect organs and tissues from acute injury. Although nitric oxide (NO)‐mediated cytoprotective effects against cytotoxicity induced by glucose deprivation have been well recognized, the underlying mechanisms remain to be elucidated. Thus, we investigate the involvement of HO‐1 in the cytoprotective effects of NO. Deprivation of glucose markedly reduced the viability of BNL CL.2 cells and primary rat hepatocytes. Pretreatment with NO donor, sodium nitroprusside (SNP), protected hepatocytes from glucose deprivation‐induced cytotoxicity; zinc protoporphyrin (ZnPP) IX, an inhibitor of HO, was found to block the SNP‐induced cytoprotection. SNP increased the induction of HO‐1 protein as well as its activity in hepatocytes. A cytoprotective effect comparable to SNP was observed when the cells were transfected with HO‐1 gene or preincubated with another HO‐1 inducer, hemin. Additional experiments revealed the involvement of CO in the cytoprotective effect of SNP/HO‐1 in BNL CL.2 cells. CO mediated cytoprotective effect through suppression of ERK MAPK activation. In conclusion, our results show that SNP protects hepatocytes from glucose deprivation‐induced cytotoxicity through up‐regulation of HO‐1. Thus, HO‐1 might be an important cellular target of NO donor with clinical implications for the prevention of acute liver injury in several pathological conditions.
Flunarizine (Sibelium) in the Prophylaxis of Migraine. An Open, Long-Term, Multicenter Trial

Sixty-four Spanish neurological centers participated in a study designed to evaluate the efficacy and safety of flunarizine in migraine. One thousand four hundred and thirty-five outpatients (367 [25.6%] males and 1,068 [74.4%] females) fulfilling the criteria proposed by the International Headache Society for the diagnosis of migraine entered the study. Patients were treated with 10 mg of single-dose flunarizine (Sibelium) alone at bedtime in open fashion for 6 months. At the end of this treatment period, flunarizine was withdrawn, but the follow-up of the patients continued for another 6 months. The evaluation criteria used were a rating scale (the GES) based on frequency, duration, intensity, and characteristics of the attacks as well as a checklist of possible side-effects. This clinical assessment was recorded in detail in the patients' rating notebooks at the start and at the end of the third, sixth, ninth, and twelfth month of the study. A mean decrease of 66.9% in the GES was obtained at the end of the treatment period, which implies a good or excellent result in the prophylaxis of migraine attacks in 69.5% of the patients. This improvement was practically unchanged at the end of the follow-up period. Side-effects were moderate, the most frequent ones being drowsiness and weight gain. Their incidence decreased after the first months of treatment.
Acute protein-calorie malnutrition impairs wound healing: a possible role of decreased wound nitric oxide synthesis.

BACKGROUND Nitric oxide is synthesized in wounds. Systemic inhibition of wound nitric oxide synthesis decreases wound collagen accumulation and wound mechanical strength. The role of nitric oxide during impaired healing is not known. In a model of impaired wound healing induced by acute protein-calorie malnutrition, we correlated wound healing parameters with wound nitric oxide synthesis. STUDY DESIGN One group of Sprague-Dawley rats was rendered acutely malnourished by restricting its food intake to 50 percent of the food intake of an ad libitum-fed control group. Wound collagen accumulation and types I and III collagen gene expression were measured 10 days postwounding in subcutaneously implanted polyvinyl alcohol sponges. Nitric oxide synthesis was determined in wound fluid and in supernatants of wound cell cultures. RESULTS Animals with acute protein-calorie malnutrition lost 10.4 +/- 0.8 percent, while controls gained 17.5 +/- 1.2 percent of their original body weight. Protein-calorie malnutrition reduced sponge hydroxyproline contents (995 +/- 84 compared with 1,580 +/- 109 micrograms/100 mg sponge, p < .001), indicating diminished wound collagen accumulation. Gene expression of type III, but not type I, collagen was decreased in wounds of protein-calorie malnutrition animals. Nitrite/nitrate and citrulline concentrations in wound fluid (p < .01) and in wound cell supernatants (p < .001) were also lower in protein-calorie malnutrition animals, indicating a net decrease in nitric oxide production. CONCLUSIONS Impaired wound collagen accumulation caused by protein-calorie malnutrition may be a reflection of reduced nitric oxide synthesis within the wound.
Failure to rescue patients after reintervention in gastroesophageal cancer surgery in England.

IMPORTANCE Gastroesophageal cancer resections are associated with significant reintervention and perioperative mortality rates. OBJECTIVE To compare outcomes following operative and nonoperative reinterventions between high- and low-mortality gastroesophageal cancer surgical units in England. DESIGN All elective esophageal and gastric resections for cancer between 2000 and 2010 in English public hospitals were identified from a national administrative database. Units were divided into low- and high-mortality units (LMUs and HMUs, respectively) using a threshold of 5% or less for 30-day adjusted mortality. The groups were compared for reoperations and nonoperative reinterventions following complications. SETTING Both LMUs and HMUs. PARTICIPANTS Patients who underwent esophageal and gastric resections for cancer. EXPOSURE Elective esophageal and gastric resections for cancer, with reoperations and nonoperative reinterventions following complications. MAIN OUTCOMES AND MEASURES Failure to rescue is defined as the death of a patient following a complication; failure to rescue-surgical is defined as the death of a patient following reoperation for a surgical complication. RESULTS There were 14 955 esophagectomies and 10 671 gastrectomies performed in 141 units. For gastroesophageal resections combined, adjusted mortality rates were 3.0% and 8.3% (P < .001) for LMUs and HMUs, respectively. Complications rates preceding reoperation were similar (5.4% for LMUs vs. 4.9% for HMUs; P = .11). The failure to rescue-surgical rates were lower in LMUs than in HMUs (15.3% vs. 24.1%; P < .001). The LMUs performed more nonoperative reinterventions than the HMUs did (6.7% vs. 4.7%; P < .001), with more patients surviving in LMUs than in HMUs (failure to rescue rate, 7.0% vs. 12.5%; P < .001). Overall, LMUs reintervened more than HMUs did (12.2% vs 9.6%; P < .001), and LMUs had lower failure to rescue rates following reintervention than HMUs did (9.0% vs. 18.3%; P = .001). All P values stated refer to 2-sided values. CONCLUSIONS AND RELEVANCE Overall, LMUs were more likely to reintervene and rescue patients following gastroesophageal cancer resections in England. Patients were more likely to survive following both reoperations and nonsurgical interventions in LMUs.
Reliable Virtual Full-Duplex Relaying in the Presence of Interrelay Interference

Interrelay interference (IRI) is known to limit the performance of virtual full-duplex (VFD) relaying schemes. Available interference cancelation schemes are unable to simultaneously improve the diversity and maintain the multiplexing gain of VFD relaying schemes in multiple antennas scenarios. In this paper, we propose a technique to improve the reliability of multiantenna VFD relaying scheme, while maintaining the multiplexing gain in the presence of IRI. In the proposed scheme, the source and interrelay channels are concatenated and their signals are jointly decoded at the relay. A superposition of the decoded messages is forwarded to the destination. To reduce the effect of IRI on the receiving relay, two suboptimal relay transmit antenna selection schemes, namely, random antenna selection and maximum capacity antenna selection, are investigated. The system capacity and outage probability bounds of the proposed scheme are derived in closed form. The diversity and multiplexing tradeoff is also characterized. The analytical and numerical results show that the proposed scheme can achieve full diversity and maintain the multiplexing gain of the full-duplex relaying scheme. Also, the proposed scheme can outperform conventional VFD relaying scheme in terms of reliability even in the presence of IRI.
Phrenic Nerve Stimulation in the Evaluation of Ventilator-Dependent Individuals with C4- and C5-Level Spinal Cord Injury

Strakowski JA, Pease WS, Johnson EW: Phrenic nerve stimulation in the evaluation of ventilator-dependent individuals with C4- and C5-level spinal cord injury. Am J Phys Med Rehabil 2007;86:153–157. Three individuals with C4 or C5 spinal cord injuries (SCI) were seen in follow-up for management of their late complications, which included impaired ventilation. Electrodiagnostic studies were performed on all three as part of the assessment of the function of their phrenic nerves and diaphragm muscles in relation to their need for mechanical ventilator support. Each patient had evidence of lower–motor neuron injury to the phrenic nerves. Two of the patients who initially displayed small-amplitude (<0.1 mV) compound muscle action potentials (CMAP) bilaterally were later reevaluated during the course of their observation in the outpatient rehabilitation clinic. The CMAP amplitude of the diaphragm increased in these two cases during the 3–11 mos after SCI. Evidence of nerve recovery occurred in parallel with improvements in pulmonary function testing and was followed by successful weaning from the ventilator. These individuals both gained ventilator independence after the CMAP amplitude of least one hemidiaphragm was >0.4 mV. In the third case, early failure of ventilator weaning was reported to the patient as a poor prognostic sign. At the time of our first evaluation 11 mos after injury, a CMAP of 1.0 mV was seen on the right, with an absent response on the left. In case 3, the needle electromyogram demonstrated voluntary active motor unit action potentials that provided additional electrophysiologic support for phrenic nerve function. Phrenic nerve–conduction studies can provide useful measures in assessing the recovery of lower–motor neuron diaphragm function in relation to impaired ventilation in individuals with C4- or C5-level SCI.
Antibodies to the trypsin cleavage peptide VP8 neutralize rotavirus by inhibiting binding of virions to target cells in culture

Two distinct patterns of neutralization were identified by comparing the neutralization curves of monoclonal antibodies (MAbs) directed at the two surface proteins, VP4 and VP7, of rhesus rotavirus. VP7-specific MAbs were able to neutralize virus efficiently, and slight increases in antibody concentration resulted in a sharp decline in infectivity. On the other hand, MAbs to VP4 proved much less efficient at neutralizing rhesus rotavirus, and the fraction of infectious virus decreased gradually throughout a wide range of antibody concentrations. MAbs directed at VP8*, the smaller trypsin cleavage fragment of VP4, were shown to efficiently prevent binding of radiolabeled virions to MA104 cell monolayers, to an extent and at concentrations comparable to those required for neutralization of infectivity. Conversely, MAbs recognizing VP7 or the larger VP4 trypsin cleavage product, VP5*, showed little or no inhibitory effect on virus binding to cells. All MAbs studied were able to neutralize rotavirus that was already bound to the surface of cells. The MAbs directed at VP8*, but not those recognizing VP5* or VP7, were shown to mediate release of radiolabeled virus from the surface of the cells. With MAbs directed at VP7, papain digestion of virus-bound antibody molecules led to an almost complete recovery of infectivity. Neutralization could be fully restored by incubation of virus-Fab complexes with anti-mouse immunoglobulin G antiserum. Neutralization with MAbs directed at VP8* proved insensitive to digestion with papain as well as to the addition of anti-immunoglobulin antibodies.
Exposure to lead appears to selectively alter metabolism of cortical gray matter.

OBJECTIVE The effects of lead poisoning on the development of children have been examined primarily in the context of behavioral and neuropsychological studies. The purpose of this study was to examine the in vivo use of magnetic resonance spectroscopy (MRS) for the evaluation of the neurotoxic effects of lead on the nervous system. MRS has the ability to monitor brain metabolism by detecting a number of neurochemicals among which is N-acetylaspartate, a metabolite shown to decrease in processes that involve neuronal loss. METHODS In the present study we evaluated the metabolism of gray and white matter of frontal cortex using MRS in individuals with elevated blood lead levels and compared the results with those obtained on nonlead-exposed controls. RESULTS Although all of the participants had normal MRI examinations of the brain, the lead-exposed individuals exhibited a significant reduction in the N-acetylaspartate/creatine and phosphocreatine ratios in frontal gray matter compared with the nonlead-exposed controls. CONCLUSIONS The findings of this study suggest that lead has an effect on brain metabolites as detected by MRS in vivo. More specifically, we have found statistically significant reduced levels of brain metabolites in gray but not white matter in lead-exposed individuals. These results imply that MRS is able to detect metabolic abnormalities in individuals with lead poisoning.
Does nanoparticle activity depend upon size and crystal phase?

A method to investigate the dependence of the physicochemical properties of nanoparticles (e.g., size, surface area and crystal phase) on their oxidant generating capacity is proposed and demonstrated for TiO2 nanoparticles. Gas phase synthesis methods that allow for strict control of size and crystal phase were used to prepare TiO2 nanoparticles. The reactive oxygen species (ROS) generating capacity of these particles was then measured. The size dependent ROS activity was established using TiO2 nanoparticles of nine different sizes (4–195 nm) but the same crystal phase. For a fixed total surface area, an S-shaped curve for ROS generation per unit surface area was observed as a function of particle size. The highest ROS activity per unit area was observed for 30 nm particles, and observed to be constant above 30 nm. There was a decrease in activity per unit area as size decreased from 30–10 nm; and again constant for particles smaller than 10 nm. The correlation between crystal phase and oxidant capacity was established using TiO2 nanoparticles of 11 different crystal phase combinations but similar size. The ability of different crystal phases of TiO2 nanoparticles to generate ROS was highest for amorphous, followed by anatase, and then anatase/rutile mixtures, and lowest for rutile samples. Based on evaluation of the entire dataset, important dose metrics for ROS generation are established. The implications of these ROS studies on biological and toxicological studies using nanomaterials are discussed.
A cost-effectiveness model comparing endovascular repair to open surgical repair of abdominal aortic aneurysms in Canada.

OBJECTIVES The primary risk of abdominal aortic aneurysms (AAAs) is rupture, which is associated with a high mortality rate. Elective surgical options for AAA include open repair (OR) and endovascular aneurysm repair (EVAR). EVAR is less invasive than OR, and therefore may have less surgical risk than OR. However, the graft used for EVAR is much more expensive then the graft used for OR. METHODS A decision model with a 10-year time horizon was used to assess the cost-effectiveness of EVAR versus OR. The primary outcome measure was quality-adjusted life-years (QALYs). The model incorporated the costs and benefits of both perioperative outcomes and postoperative outcomes. A systematic review was conducted to derive clinical outcome rates. Cost and utility model variables were based on various literature sources and data from a recent Canadian observational study. Parameter uncertainty was assessed using probabilistic sensitivity analysis. RESULTS In the base-case model, the incremental cost per QALY of EVAR was estimated to be $268,337, whereas the incremental cost per life-year was found to be $444,129. The incremental cost per QALY of EVAR remained above $295,715 under different assumptions of cohort age and model time horizon. CONCLUSIONS Based on commonly quoted willingness-to-pay thresholds, EVAR was not found to be cost-effective compared to OR.
Dietary Folate, Riboflavin, Vitamin B-6, and Vitamin B-12 and Depressive Symptoms in Early Adolescence: The Ryukyus Child Health Study

Objective: To examine the association between dietary folate, riboflavin, vitamin B-6, and vitamin B-12 and depressive symptoms in a group of adolescents. Methods: This cross-sectional study, conducted in all public junior high schools in Naha City and Nago City, Okinawa, Japan, included 3,067 boys and 3,450 girls aged 12 years to 15 years (52.3% of eligible sample). Dietary intake was assessed using a validated, self-administered diet history questionnaire. Depressive symptoms were defined as present when participants had a Center for Epidemiologic Studies Depression Scale score of ≥16. Results: The prevalence of depressive symptoms was 22.5% for boys and 31.2% for girls. Folate intake was inversely associated with depressive symptoms in both boys (adjusted odds ratio (OR) [95% confidence interval (CI)] in the highest (compared with the lowest) quintile, 0.60 [0.45, 0.79]; p for trend = . 002) and girls (OR [95% CI], 0.61 [0.48, 0.77]; p for trend = <.001). Vitamin B-6 intake was inversely associated with depressive symptoms in both boys (OR [95% CI], 0.73 [0.54, 0.98]; p for trend = .02) and girls (OR [95% CI], 0.72 [0.56, 0.92]; p for trend = .002). Riboflavin intake was inversely associated with depressive symptoms in girls (OR [95% CI], 0.85 [0.67, 1.08]; p for trend = .03), but not in boys. No clear association was seen between vitamin B-12 intake and depressive symptoms in either sex. Conclusions: This study suggests that higher intake of dietary B vitamins, particularly folate and vitamin B-6, is independently associated with a lower prevalence of depressive symptoms in early adolescence. BDHQ = brief self-administered diet history questionnaire; CES-D = Center for Epidemiologic Studies Depression Scale; CI = confidence interval; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; OR = odds ratio; RYUCHS = Ryukyus Child Health Study.
Impact of moderate coronary atherosclerosis on long-term left ventricular remodeling after aortic valve replacemen.

BACKGROUND The role of coronary atherosclerosis (CA+) in ventricular remodeling after aortic valve replacement (AVR) for isolated aortic stenosis (AS) is not well defined. We sought to evaluate the impact of not revascularized moderate coronary atherosclerosis in long-term left ventricular (LV) remodeling after AVR. METHODS We assessed by coronariography the coronary artery disease in 66 patients referred for AVR and evaluated morphological and functional LV data by echocardiography both preoperatively and postoperatively (3 ± 1.2 years). RESULTS In patients without coronary atherosclerosis, hypertrophy regression was more intense and the absolute reverse remodeling was higher in LV mass index (-55.8 ± 36 g/m² vs -28.4 ± 34 g/m², p = 0.004), reduction of LV dimensions (LV end-diastolic diameter [LVEDD]: -4.1 ± 7.4 mm vs -2.2 ± 8.3 mm, p = 0.04), and regression of wall thickness (interventricular septum [IVS]: -3.3 ± 2.6 mm vs -1.6 ± 2.2 mm, p = 0.01; and posterior wall thickness [PWT]: -2.1 ± 2.1 mm vs 0.6 ± 2.1 mm, p = 0.012). CONCLUSIONS After AVR for AS, not revascularized moderate coronary atherosclerosis determines a long-term lesser degree of LV hypertrophy regression and a worse absolute reverse remodeling of LV mass index, LVEDD, IVS and PWT.
RM Pressfit® Cup: Good Preliminary Results at 5 to 8 Years Follow-Up for 189 Patients

Aim The RM Classic® cup shows very good results. The RM Pressfit® cup has an equatorial pressfit; it is a monoblock implant without metalback. The aim of this study was to evaluate retrospectively the survival of this implant, monitoring patients for at least 5 years in all consecutive cases operated in our centre. Methods Between February 2006 and December 2008, our department performed 189 consecutive nonselected primary total hip arthroplasties using the RM® Pressfit cup, and all of these were included in the study. The operative technique involved an anterolateral approach. The latest follow-up evaluation was performed at a minimum of 5 years after the index arthroplasty. Results The mean follow-up was 6.5 years (5-8 years). We had preoperative information for 186 of the 189 patients. 102 patients were seen in consultation (54.0%), 46 (24.3%) patients were contacted by phone, 37 (19.6%) patients died, and 4 patients (2.1%) were lost for unknown reasons. Of the 189 arthroplasties, 6 (3.2%) required revision; 4 (2.1%) for infection, 1 (0.5%) for significant haematoma with persistent deglobulisation and 1 (0.5%) for periprosthetic calcification during the 5 to 8 years following the operation. No hip was revised because of aseptic loosening. The mean annual wear rate based on the last follow-up at 5 years minimum was 0.065 mm per year. We observed no migration, 1 femoral loosening and no acetabular loosening. Conclusions Our study finds a good survival rate which is compatible with the 94% at 20 years with RM Classic®. These results are suggestive but must be confirmed with long-term studies.
Human herpesvirus 8 seroprevalence and viral load in healthy adult blood donors

BACKGROUND : Human herpesvirus 8 (HHV‐8) is widely suspected to be a human tumor virus because it is associated with Kaposi's sarcoma and primary effusion B cell lymphoma. Report of a case of HHV‐8‐positive donor blood in the US has led to concern for the safety of donor blood from HHV‐8‐seropositive donors.
Light and electron microscopic evidence for a GABAergic projection from the caudal basal forebrain to the thalamic reticular nucleus in rats

Neurons in the magnocellular nucleus of the caudal basal forebrain extend an axonal projection which arborizes within the reticular nucleus of the thalamus. The present study addresses the ultrastructure and neurochemistry of this projection in rats. Many labeled terminals are apparent within the thalamic reticular nucleus following Phaseolus vulgaris leucoagglutinin injections into the caudal basal nucleus; anterogradely labeled axon terminals most commonly contact both somata and dendrites of reticular nucleus neurons with symmetric membrane specializations. Thus, the majority of the labeled terminals examined contrast with choline acetyltransferase positive terminals which have been previously identified as contacting dendrites and forming asymmetric synapses within this nucleus.