Miracle-dz/UniFAR-FTUs huggingface dataset:
Marked Differences between Metalloproteases Meprin A and B in Substrate and Peptide Bond Specificity*

Meprin A and B are highly regulated, secreted, and cell-surface metalloendopeptidases that are abundantly expressed in the kidney and intestine. Meprin oligomers consist of evolutionarily related α and/or β subunits. The work herein was carried out to identify bioactive peptides and proteins that are susceptible to hydrolysis by mouse meprins and kinetically characterize the hydrolysis. Gastrin-releasing peptide fragment 14–27 and gastrin 17, regulatory molecules of the gastrointestinal tract, were found to be the best peptide substrates for meprin A and B, respectively. Peptide libraries and a variety of naturally occurring peptides revealed that the meprin β subunit has a clear preference for acidic amino acids in the P1 and P1′ sites of substrates. The meprin α subunit selected for small (e.g. serine, alanine) or hydrophobic (e.g. phenylalanine) residues in the P1 and P1′ sites, and proline was the most preferred amino acid at the P2′ position. Thus, although the meprin α and β subunits share 55% amino acid identity within the protease domain and are normally localized at the same tissue cell surfaces, they have very different substrate and peptide bond specificities indicating different functions. Homology models of the mouse meprin α and β protease domains, based on the astacin crystal structure, revealed active site differences that can account for the marked differences in substrate specificity of the two subunits.
Spatial patterns of off-the-system traffic crashes in Miami–Dade County, Florida, during 2005–2010

ABSTRACT Objective: The objective of this study is to analyze the spatial distribution of the vehicles involved in crashes in Miami–Dade County. In addition, we analyzed the role of time of day, day of the week, seasonality, drivers’ age in the distribution of traffic crashes. Method: Off-the-system crash data acquired from the Florida Department of Transportation during 2005–2010 were divided into subcategories according to the risk factors age, time of day, day of the week, and travel season. Various spatial statistics methods, including nearest neighbor analysis, Getis-Ord hot spot analysis, and kernel density analysis revealed substantial spatial variations, depending on the subcategory in question. Results: Downtown Miami and South Beach showed up consistently as hotspots of traffic crashes in all subcategories except fatal crashes. However, fatal crashes were concentrated in residential areas in inland areas. Conclusion: This understanding of patterns can help the county target high-risk areas and help to reduce crash fatalities to create a safer environment for motorists and pedestrians.
The Effect of Oral Niacinamide on Plasma Phosphorus Levels in Peritoneal Dialysis Patients

Background Hyperphosphatemia remains a significant problem for patients requiring dialysis and is associated with increased mortality. Current treatment options include dietary restriction, dialysis, and phosphate binders. Treatment using the latter is frequently limited by cost, tolerability, and calcium loading. One open-label trial found niacinamide to be effective at decreasing serum phosphorus values in hemodialysis patients. Niacinamide may effectively reduce phosphorus levels in peritoneal dialysis (PD) patients already receiving standard phosphorus-lowering therapies. Methods An 8 week, randomized, double blind, placebo-controlled trial to evaluate the effectiveness of niacinamide to reduce plasma phosphorus levels in PD patients. Patients had to demonstrate a baseline phosphorus value > 4.9 mg/dL. Patients were randomized to niacinamide or placebo and prescribed 250 mg twice daily, with titration to 750 mg twice daily, as long as safety parameters were not violated. Phosphate binders, active vitamin D, and cinacalcet were kept constant during the study. The primary end point was change in plasma phosphorus. Secondary end points included changes in lipid parameters. Results 15 patients started on the study drug (8 niacinamide, 7 placebo) and 7 in each arm had at least one on-study phosphorus measurement. The niacinamide treatment group experienced an average 0.7 ± 0.9 mg/dL decrease in plasma phosphorus and the placebo-treated group experienced an average 0.4 ± 0.8 mg/dL increase. The treatment effect difference (1.1 mg/dL) was significant (p = 0.037). No significant changes in high- or low-density lipoproteins or triglycerides were demonstrated. Two of the 8 patients randomized to the niacinamide treatment arm had to withdraw from the study due to drug-related adverse effects. Adverse effects may limit the use of niacinamide in PD patients. Conclusion Niacinamide, when added to standard phosphorus-lowering therapies, resulted in a modest yet statistically significant reduction in plasma phosphorus levels at 8 weeks. [ClinicalTrials.gov number NCT00508885 (ClinicalTrials.gov)]
Pressure ulcer risk assessment in long-term care nursing.

The intent of this study was to determine whether the typical practice of using risk assessment tools in combination with the federally mandated Minimum Data Set (MDS) actually predict more cases of pressure ulcers (PUs) in long-term care facilities. Data in this study were collected from 555 resident charts in a sample of eight nursing homes. A total of 66 PUs were identified between September 1, 1996 and September 1, 1997 in a comparative test of the predictive abilities of the MDS versus the Braden Scale (BS) patient profiles. As shown by a Chi square test, the MDS and the BS assessment tools were valid in finding factors that placed residents in jeopardy of developing pressure ulcers: MDS chi 2 = 43.68, df = 1, p < . 0001 and BS chi 2 = 52.47, df = 1, p < . 001. However, a two-tailed t test, indicated results of the BS were significantly different than the MDS: t = 3.77, df = 97, p < . 003 and BS = t = 3.77, df = 97, p < . 001. Both the MDS and the BS identified patient factors: the MDS identified 311 at risk, resulting in accurate prediction of 62 of 66 PUs, while the BS found 172 at risk and predicted only 46 PUs accurately. Therefore, data indicate the BS did not make a significant difference in predicting the incidence of pressure ulcers in this sample of long-term care facilities. These unexpected findings would argue in favor of discontinuing the practice of using the BS for PU risk assessment simultaneously with the MDS, but rather at independent time frames such as immediately upon resident admission. This would continue to support the recommendations of the National Pressure Ulcer Advisory Panel (NPUAP), and at the same time, provide a more timely pressure ulcer risk assessment.
Transgenic Mouse with the Herpes Simplex Virus Type 1 Latency-Associated Gene: Expression and Function of the Transgene

ABSTRACT During herpes simplex virus type 1 (HSV-1) latent infection in human peripheral sensory ganglia, the major viral gene transcribed is the latency-associated transcript (LAT) gene. In order to facilitate the study of this gene, we generated a transgenic mouse that contains the DNA fragment that transcribes the LAT RNAs (2.0 kb and its 1.5-kb spliced transcript) under control of the cytomegalovirus promoter. The tissue distribution of these transcripts and their effects upon HSV-1 replication, latency, and reactivation in the transgenic-mouse model were examined. Different steady-state amounts of both transcripts were found in various tissues. While the highest levels of the 2.0-kb RNA were detected in heart and skeletal muscle, the 1.5-kb transcript was found at elevated levels in the brain and at much higher levels in the trigeminal ganglia (TG). Replication of both the wild-type and a LAT-negative mutant virus was suppressed in primary embryonic fibroblasts obtained from LAT-expressing transgenic mice compared to that in cells obtained from normal mice. HSV-1 DNA amounts in latently infected TG of transgenic mice were similar to those in normal mice. Reactivation of latent HSV-1 LAT-negative mutants by explant cocultivation of TG from transgenic mice was more efficient than reactivation from normal-mouse TG. Considering our present and previous results, we propose that the significantly higher steady-state level of the 1.5-kb RNA in the TG may link this transcript to latency functions and that by inhibition of virus replication, the LAT gene may protect ganglion cells and thereby increase the probability of reactivation.
Delayed Microvascular Shear Adaptation in Pulmonary Arterial Hypertension. Role of Platelet Endothelial Cell Adhesion Molecule-1 Cleavage.

RATIONALE Altered pulmonary hemodynamics and fluid flow-induced high shear stress (HSS) are characteristic hallmarks in the pathogenesis of pulmonary arterial hypertension (PAH). However, the contribution of HSS to cellular and vascular alterations in PAH is unclear. OBJECTIVES We hypothesize that failing shear adaptation is an essential part of the endothelial dysfunction in all forms of PAH and tested whether microvascular endothelial cells (MVECs) or pulmonary arterial endothelial cells (PAECs) from lungs of patients with PAH adapt to HSS and if the shear defect partakes in vascular remodeling in vivo. METHODS PAH MVEC (n = 7) and PAH PAEC (n = 3) morphology, function, protein, and gene expressions were compared with control MVEC (n = 8) under static culture conditions and after 24, 72, and 120 hours of HSS. MEASUREMENTS AND MAIN RESULTS PAH MVEC showed a significantly delayed morphological shear adaptation (P = 0.03) and evidence of cell injury at sites of nonuniform shear profiles that are critical loci for vascular remodeling in PAH. In clear contrast, PAEC isolated from the same PAH lungs showed no impairments. PAH MVEC gene expression and transcriptional shear activation were not altered but showed significant decreased protein levels (P = 0.02) and disturbed interendothelial localization of the shear sensor platelet endothelial cell adhesion molecule-1 (PECAM-1). The decreased PECAM-1 levels were caused by caspase-mediated cytoplasmic cleavage but not increased cell apoptosis. Caspase blockade stabilized PECAM-1 levels, restored endothelial shear responsiveness in vitro, and attenuated occlusive vascular remodeling in chronically hypoxic Sugen5416-treated rats modeling severe PAH. CONCLUSIONS Delayed shear adaptation, which promotes shear-induced endothelial injury, is a newly identified dysfunction specific to the microvascular endothelium in PAH. The shear response is normalized on stabilization of PECAM-1, which reverses intimal remodeling in vivo.
Epidural administration of bupivacaine, morphine, or their combination for postoperative analgesia in dogs.

OBJECTIVE To compare the analgesic effects of epidural administration of morphine (MOR), bupivacaine hydrochloride (BUP), their combination (COM), and 0.9% sterile NaCl solution (SAL) in dogs undergoing hind limb orthopedic surgeries. DESIGN Blinded, randomized clinical trial. ANIMALS 41 healthy dogs admitted for elective orthopedic surgeries involving the pelvis or hind limbs. PROCEDURE Analgesic and control agents were administered postoperatively prior to recovery from isoflurane anesthesia. Ten dogs received MOR, 0.1 mg/kg of body weight; 10 received BUP, 0.5%, 1 ml/10-cm distance from the occipital protuberance to the lumbosacral space; 11 received COM; and 10 received SAL epidurally. Dogs were monitored for 24 hours after epidural injection for pain score, heart and respiratory rates, blood pressure, time to required administration of supplemental analgesic agent, total number of supplemental doses of analgesic agent required, and plasma concentrations of cortisol, MOR, and BUP. RESULTS Pain scores were significantly lower in dogs in the COM and BUP groups than in dogs in the SAL group. Pain scores also were significantly lower in dogs in the COM group than in dogs in the MOR group. Time to required administration of supplemental analgesic agent was longer for dogs in the COM group than for dogs in the MOR and SAL groups. Total number of supplemental doses of analgesic agent required was lower for dogs in the BUP and COM groups than for dogs in the SAL group. CLINICAL IMPLICATIONS Postoperative epidural administration of COM or BUP alone provides longer-lasting analgesia, compared with MOR or SAL.
Hypnosis and biofeedback in the treatment of migraine headache.

Abstract A study was made to explore the decta of subject-hypnotizability in response to 3 treatment procedures applied to 33 migraine headache sufferers. These treatment procedures included biofeedback training for hand-warming, biofeedback training for alpha enhancement, and training for self-hypnosis. The Hypnotic Induction Profile (HIP) of Spiegel & Bridger (1970) was given to each s to determine degree of hypnotizability and the MMF'I was administered to all 8s. All 3 treatment groups showed aigdicant reductions in headache rates and there were no gignificant differences between groups. Cutting acros treatment groups, high hypnotizable Ss (N = 15) showed significant reductions in headache rates when compared with low hypnotizable Ss (N = 13). There was no correlation between HIP scores and the hysteria scale of the MMPI.
Effects of subclinical pregnancy toxemia on immune responses in sheep.

OBJECTIVE To determine the effects of moderate feed restriction, single or twin pregnancy, and subclinical pregnancy toxemia (PT) on immune responses of ewes. ANIMALS 16 Sardinian ewes. PROCEDURE Six weeks before lambing, ewes were assigned to 1 of 2 groups (n = 8/group) matched for number of fetuses, body condition score, and plasma glucose, non-esterified fatty acids (NEFA), and beta hydroxybutyrate (BHBA) concentrations, and feed intake was restricted for 1 of the groups. Cell-mediated immunity was evaluated in vivo and in vitro. Humoral immunity was evaluated in vivo by determining production of IgG antibodies against keyhole limpet hemocyanin (KLH). RESULTS Four ewes developed subclinical PT (plasma BHBA concentration > 0.86 mmol/L without any clinical signs of disease). Whether feed was restricted and type of pregnancy (single vs twin) did not have any significant effects on cell-mediated and humoral immune responses. Ewes with subclinical PT had significantly lower in vitro proliferation of phytohemagglutinin-stimulated peripheral blood mononuclear cells and significantly lower values for KLH-specific IgG than did healthy ewes. Plasma BHBA and NEFA concentrations were negatively correlated with in vitro proliferation of peripheral blood mononuclear cells; plasma NEFA concentration was negatively correlated with values for KLH-specific IgG. CONCLUSIONS AND CLINICAL RELEVANCE Results suggest that subclinical PT may be associated with impairments in cell-mediated and humoral immune responses in sheep.
Sinus mucosa elevation using Bio‐Oss® or Gingistat® collagen sponge: an experimental study in rabbits

OBJECTIVE To describe the sequential healing in augmented sinus cavities with deproteinized bovine bone mineral (DBBM) granules or collagen sponges. MATERIAL AND METHODS Twenty albino New Zealand rabbits were included in the study. An incision was performed along the midline of the nasal dorsum, and the nasal bone was exposed. Circular bony windows with a diameter of 5 mm were prepared bilaterally. After elevation of the mucosa, the two sites were randomly filled with either DBBM or a collagen sponge. Five animals each were randomly sacrificed after 7, 14, 21 and 40 days, respectively. RESULTS At both sides, new bone was found forming from the resident pristine bone. During the first stage of healing, DBBM granules were surrounded by a denser connective tissue that was attached to the biomaterial surface and that was progressively mineralized. At the collagen sponge side, the biomaterial was almost completely resorbed and the space was reduced by to two-thirds already after 21 days. At both sides, after 40 days, mineralized bone and marrow spaces were occupying large areas of the elevated space. CONCLUSIONS New bone was found forming from the pristine bony walls of the sinus and extending toward the most peripheral regions in both sites. While DBBM particles yielded osteoconductivity and were able to preserve over time the space within the elevated mucosa, the collagen sponge failed the goal of maintaining the space.
Interaction with Btn2p Is Required for Localization of Rsg1p: Btn2p-Mediated Changes in Arginine Uptake in Saccharomyces cerevisiae

ABSTRACT Btn2p, a novel coiled-coil protein, is up-regulated in btn1Δ yeast strains, and this up-regulation is thought to contribute to maintaining a stable vacuolar pH in btn1Δ strains (D. A. Pearce, T. Ferea, S. A. Nosel, B. Das, and F. Sherman, Nat. Genet. 22:55-58, 1999). We now report that Btn2p interacts biochemically and functionally with Rsg1p, a down-regulator of the Can1p arginine and lysine permease. Rsg1p localizes to a distinct structure toward the cell periphery, and strains lacking Btn2p (btn2Δ strains) fail to correctly localize Rsg1p. btn2Δ strains, like rsg1Δ strains, are sensitive for growth in the presence of the arginine analog canavanine. Furthermore, btn2Δ strains, like rsg1Δ strains, demonstrate an elevated rate of uptake of [14C]arginine, which leads to increased intracellular levels of arginine. Overexpression of BTN2 results in a decreased rate of arginine uptake. Collectively, these results indicate that altered levels of Btn2p can modulate arginine uptake through localization of the Can1p-arginine permease regulatory protein, Rsg1p. Our original identification of Btn2p was that it is up-regulated in the btn1Δ strain which serves as a model for the lysosomal storage disorder Batten disease. Btn1p is a vacuolar/lysosomal membrane protein, and btn1Δ suppresses both the canavanine sensitivity and the elevated rate of uptake of arginine displayed by btn2Δ rsg1Δ strains. We conclude that Btn2p interacts with Rsg1p and modulates arginine uptake. Up-regulation of BTN2 expression in btn1Δ strains may facilitate either a direct or indirect effect on intracellular arginine levels.
Nutritional Support in Acute Pancreatitis: An Update on Management Issues

About 20% of acute pancreatitis cases develop necrosis and have a high risk of inflammatory and infectious complications and a high mortality rate. Acute pancreatitis has a variety of causes and despite years of research its pathogenesis remains complex and obscure. Both local and systemic inflammatory responses play key roles in the pathophysiology of this disorder. Treatment plans continue to rely on supportive care without proven specific therapies. Pancreatic rest and use of total parenteral nutrition (TPN) were the gold standard for nutritional support of these challenging patients. Because numerous studies in other critically ill patients demonstrated benefits of enteral nutrition, recent investigations compared TPN to enteral nutrition in acute pancreatitis. These studies indicated that enteral nutrition delivered into the jejunum was tolerated well, even in patients with severe acute pancreatitis. "Mild'' cases of pancreatitis should improve and tolerate oral nutrition within a few days. In contrast, "severe'' cases of pancreatitis or those with a protracted clinical course require nutritional support to aid in preventing adverse effects of starvation and nutrient deficiencies. Current recommendations are to attempt enteral nutrition in patients with acute pancreatitis prior to instituting TPN. Further studies to determine optimal nutrient composition are warranted and should investigate the possibility of modulating the inflammatory response induced by pancreatitis to improve outcomes.
Age Differences in Positive Feelings and Their Expression

Although various studies point to the importance of positive emotions for health and well-being across the entire life span, current research on age differences in emotional reactivity mainly focuses on negative emotions. Empirical evidence on positive emotions is scarce and mixed. Part of the inconsistencies may be related to study differences in the stimuli used and the emotional response systems considered. Thus, the present study examined different response systems (i.e., subjective feelings, facial and verbal expressions) and used internal stimuli of high personal relevance to all participants. More specifically, we used a modified relived emotion task in which younger (M = 25.64, SD = 4.05) and older (M = 70.06, SD = 3.94) adults first privately relived emotions associated with a recent positive event in their life, and subsequently thought aloud about this event and its accompanying feelings. We additionally explored whether conscientiousness, as a marker of self-regulatory skills, is associated with interindividual and age-related differences in positive emotions. During the relived emotion task, there were no age differences in positive feelings; however, compared with young adults, older adults reported more positive feelings during the think-aloud phase. Contrary to our prediction, however, older adults verbally and nonverbally expressed fewer positive emotions than their younger counterparts. Moreover, conscientiousness was associated with individual and age-related differences in positive feelings, pointing to the potential explanatory role of self-regulatory skills in the experience of positive emotions.
Cholesterol efflux capacity does not associate with coronary calcium, plaque vulnerability, and telomere length in healthy octogenarians[S]

Several studies have revealed that traditional risk factors are less effective in predicting CVD risk in the elderly, suggesting the need to identify new biomarkers. Here, we evaluated the association between serum cholesterol efflux capacity (CEC), an atheroprotective property of HDL recently identified as a novel marker of CVD risk, and atherosclerotic burden in a cohort of very old, healthy individuals. Serum CEC values were not significantly correlated either with calcium score or with markers of vulnerable plaque, such as positive remodeling, hypodensity, spotty calcification, or napking-ring sign. In addition, no association was detected between CEC and telomere length, a marker of biological aging that has been linked to atherosclerosis extent. Interestingly, elderly subjects presented a remarkably higher CEC (+30.2%; P < 0.0001) compared with values obtained from a cohort of sex-matched, cardiovascular event-free, middle-aged individuals. In conclusion, serum CEC is not related to traditional risk factors in very old, cardiovascular event-free subjects, but has significantly higher values compared with a healthy, younger population. Whether this improved HDL functionality may represent a protective factor in CVD onset must be established in future studies.
Advances in pharmacotherapy for pediatric anxiety disorders

Pediatric anxiety disorders are prevalent, chronic, and often lead to significant impaired functioning that impacts both short‐ and long‐term outcomes for children and adolescents. Treatment options include pharmacotherapy and psychosocial interventions. This presentation will review treatment advances specifically for pharmacotherapy. Current research supports serotonin reuptake inhibitors as the medication class to be the first‐line treatment option for pediatric anxiety disorders. Available evidence for the efficacy of other classes of medications will be reviewed, along with the available approaches to manage partial responders and nonresponders. The risks and benefits of pharmacotherapy will also be reviewed. In addition, recent research has shown the potential promise of novel agents that act upon other neural systems implicated in the development of pediatric anxiety disorders. Novel compounds that affect the glutamate system will be discussed. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.