Miracle-dz/UniFAR-FTUs huggingface dataset:
The significance of tissue‐type plasminogen activator for pretransplant assessment of liver graft viability: analysis of effluent from the graft in rats

Abstracts We studied the significance of tissue‐type plasminogen activator (tPA) on the pretransplant assessment of liver graft viability in rats. The liver grafts were excised from the rats and then divided into two groups. Group 1 consisted of grafts preserved for 4 h in chilled, lactated Ringer's solution (4d̀C) and group 2 consisted of grafts preserved for 6 h in the same solution. After preservation, the liver grafts were flushed out through the portal vein using 5 ml of chilled, lactated Ringer's solution (4d̀C). The entire effluent from the hepatic veins was then collected and analyzed for tPA, ammonia, lactate, pyruvate, glutamic oxaloacetic transaminase, and lactate dehydrogenase. The tPA concentration of effluent in group 2 was significantly higher than that in group 1 (0.80±0.23 ng/ml vs 0.42±0.08 ng/ml, P < 0.05). The lactate, pyruvate, and ammonia levels in group 2 were also higher than those in group 1 (134±13 mg/dl vs 120±2 mg/dl, 0.34±0.40 mg/dl vs 0.09±0.01 mg/dl, and 183±79 μ/dl vs 102±40 μ/dl, respectively). However, the discriminative power of tPA was stronger than that of the other parameters. Histological findings revealed a higher number of try‐pan blue‐stained sinusoidal lining cells that were detached and swollen in group 2. We conclude that the amount of tPA in the effluent flushed from the graft can serve as a sensitive and reliable indicator of cold‐preserved liver grafts in rats.
Overproduction of glycolytic enzymes in yeast

Eight different enzyymes for glycolysis and alcoholic fermentation were overproduced in a common Saccharomyces cerevisiae strain by placing their genes on multicopy vectors. The specific enzyme activities were increased between 3·7‐and 13·9‐fold above the wild‐type level. The overproduction of the different glycolytic enzymes had no effect on the rate of ethanol formation, even with those enzymes that catalyse irreversible steps: hexokinase, phosphofructokinase and pyruvate kinase. Also the simultaneous increase in the activities of pairs of enzymes such as pyruvate kinase and phosphofructokinase or pyruvate decarboxylase and alcohol dehyrogenase, did not increase the rate of ethanol production. The levels of key glycolytic metabolites were also normal, compared to the reference strain.
Effect of Inhibition of Deoxyribonucleic Acid and Protein Synthesis on the Direction of Cell Wall Growth in Streptococcus faecalis

Selective inhibition of protein synthesis in Streptococcus faecalis (ATCC 9790) was accompanied by a rapid and severe inhibition of cell division and a reduction of enlargement of cellular surface area. Continued synthesis of cell wall polymers resulted in rapid thickening of the wall to an extent not seen in exponential-phase populations. Thus, the normal direction of wall growth was changed from a preferential feeding out of new wall surface to that of thickening existing cell surfaces. However, the overall manner in which the wall thickened, from nascent septa toward polar regions, was the same in both exponential-phase and inhibited populations. In contrast, selective inhibition of deoxyribonucleic acid (DNA) synthesis using mitomycin C was accompanied by an increase in cellular surface area and by division of about 80% of the cells in random populations. Little or no wall thickening was observed until the synthesis of macromolecules other than DNA was impaired and further cell division ceased. Concomitant inhibition of both DNA and protein synthesis inhibited cell division but permitted an increase in average cell volume. In such doubly inhibited cells, walls thickened less than in cells inhibited for protein synthesis only. On the basis of the results obtained, a model for cell surface enlargement and cell division is presented. The model proposes that: (i) each wall enlargement site is influenced by an individual chromosome replication cycle; (ii) during chromosome replication peripheral surface enlargement would be favored over thickening (or septation); (iii) a signal associated with chromosome termination would favor thickening (and septation) at the expense of surface enlargement; and (iv) a factor or signal related to protein synthesis would be required for one or more of the near terminal stages of cell division or cell separation, or both.
Trauma Attending in the Resuscitation Room: Does it Affect Outcome?

Although there are no Class I data supporting the regionalization of trauma care the consensus is that trauma centers decrease morbidity and mortality. However, the controversy continues over whether trauma surgeons should be in-house or take call from home. The current literature does not answer the question because in all of the recent studies the attendings who took call from home were in the resuscitation room guiding the care. We believe the correct question is: Does the presence of the trauma attending in the resuscitation room make a difference? At a university-affiliated Level II trauma center data from the trauma registry, resuscitation room flowsheet, and dictated admission notes were reviewed on all patients over a 6-month period. Data points were: attending present in the resuscitation room, standard demographics, resuscitation room time, time to operating room (OR), time to CT scan, length of stay, complications, and mortality. A total of 943 patients were studied with 216 (23%) having the attending present in the resuscitation room and 727 (77%) without the attending present. The groups were similar in terms of age, sex, Injury Severity Score, percentage Injury Severity Score greater than 15 (16–17.1%), and mechanism of injury (24–29% penetrating). Of all the data points studied only time to the OR had a statistically significance difference (P < 0.05) with it taking 43.8 minutes (±20.1) when the attending was present and 109.4 minutes (±107) when the attending was absent. There were also no missed injuries, delays to the OR, or inappropriate workups when the attendings were present. Only the time to the OR reached statistical significance. The time to the OR is indicative of the decisionmaking process in the resuscitation room, and it is in this area that the attendings’ presence is the most useful. Also, we believe that it is important that there were no missed injuries, delays to the OR, or inappropriate workups when the attendings were present in the resuscitation room. This again speaks to the decision-making process. We believe that these data support the need for the attending to be present in the resuscitation room to facilitate accurate and timely decisions regardless of whether they take the call from home or in-house.
Vitamin D 3 Inhibits Hedgehog Signaling and Proliferation in Murine Basal Cell Carcinomas

Constitutive Hedgehog (HH) signaling underlies several human tumors, including basal cell carcinoma (BCC). Recently, Bijlsma and colleagues reported a new biologic function for vitamin D3 in suppressing HH signaling in an in vitromodel system. On the basis of that work, we have assessed effects of vitamin D3 on HH signaling and proliferation of murine BCCs in vitro and in vivo. We find that indeed in BCC cells, vitamin D3 blocks both proliferation and HH signaling as assessed by mRNA expression of the HH target gene Gli1. These effects of vitamin D3 on Gli1 expression and on BCC cell proliferation are comparable to the effects of cyclopamine, a known inhibitor of the HH pathway. These results are specific for vitamin D3, because the precursor 7-dehydrocholesterol and the downstream products 25-hydroxy vitamin D3 [25 (OH)D] and 1,25-dihydroxy vitamin D3 [1,25(OH)2D] are considerably less effective in reducing either Gli1 mRNA or cellular proliferation. Moreover, these effects seem to be independent of the vitamin D receptor (VDR) because short hairpin RNA knockdown of VDR does not abrogate the anti-HH effects of D3 despite reducing expression of the VDR target gene 24-hydroxylase. Finally, topical vitamin D3 treatment of existing murine BCC tumors significantly decreasesGli1 and Ki67 staining. Thus, topical vitamin D3 acting via its HH inhibiting effect may hold promise as an effective anti-BCC agent. Cancer Prev Res; 4(5); 744–51. 2011 AACR.
A Co-operative Inquiry Into Generating, Describing, and Transforming Knowledge About De-escalation Practices in Mental Health Settings

De-escalation is concerned with managing violent behaviour without resorting to coercive measures. Co-operative Inquiry provided the conceptual basis for generating knowledge regarding de-escalation practices in acute mental health care settings. The research included service users and staff members as co-researchers and knowledge was generated in dynamic research cycles around an extended epistemology of knowing: experiential, presentational, propositional, and practical. Through this process, co-researchers became de-escalation learners, implementing de-escalation practices while transforming violence management. Neighbouring mental health communities’ involvement strengthened the transformation process and assisted in validating the research results.
Role of the laparoscopic approach to cytoreductive nephrectomy in metastatic renal-cell carcinoma: does size matter?

BACKGROUND AND PURPOSE Retrospective studies have shown laparoscopic cytoreductive nephrectomy (LCN) to be a safe procedure in selected patients. The objective of this article is to identify characteristics that may predict when a laparoscopic procedure may offer improved postoperative outcome and whether it affects the timing of postoperative systemic therapy compared with open surgery. PATIENTS AND METHODS A cohort of 43 LCN cases were matched with 43 open cytoreductive nephrectomy (OCN) cases based on both pathologic size of tumor and stage. Eleven cases were laparoscopic converted to open nephrectomy. Cases excluded from the analysis were adjacent organ involvement, inferior vena cava involvement, and bulky lymphadenopathy. Data analysis of 11 variables was performed using the t test, log-rank, and Wilcoxon tests. Significance was at P = 0.05. Survival data were calculated using the Kaplan-Meier estimate. RESULTS Significant differences between LCN vs OCN were estimated blood loss (mean 277 ml vs 816 ml) and length of hospitalization (3.2 days vs 5.1 days). The median size of tumor for LCN cases was 7.5 cm and for OCN, 9.5 cm. The mean size of tumor of LCN vs laparoscopic converted to open cases was 6.8 cm vs 11.2 cm, and this difference was significant. There was no significant difference in postoperative performance status, time to commencement of systemic treatment, or in survival time between both groups. This study provides further evidence that a laparoscopic approach with cytoreductive nephrectomy in metastatic renal-cell carcinoma is a safe option for tumors 10 cm and smaller. The approach (laparoscopic vs open) had no effect on postoperative complications or time to systemic therapy. CONCLUSION Procedures with tumors larger than 10 cm were more likely to be converted to an open procedure. Tumors larger than 10 cm may be best approached via an open procedure, especially in the presence of involvement of adjacent organs or bulky lymphadenopathy.
Competition and regulation.

Perhaps as a reflection of the current medical care environment and governmental budgetary stringencies, cost containment is a major source of policy concern. There are some who would argue that one should have a comprehensive understanding of how the medical care system works in order to design appropriate policies to improve its performance. As other articles in this volume demonstrate, there is still much we do not know about individual aspects of the medical care system, and no article even attempts a comprehensive discussion of the system. Policymakers, however, cannot await research findings, and there have been numerous policy interventions in the last two decades aimed at cost containment.
What do we really know about witness preparation?

Witnesses often meet with an attorney or witness preparation specialist before trial to review, discuss, and sometimes modify the substance and delivery of their anticipated testimony. This process is commonly referred to as witness preparation. During witness preparation, witnesses are taught to use effective testimony delivery skills (e.g., verbal and nonverbal communication skills) so that they will be perceived as being credible and persuasive in the courtroom. Although social scientists know much about communication skills, credibility, and persuasion, few published studies have attempted to determine whether or not these factors can be modified through witness preparation training. The present article reviews the psychological literature pertaining to witness preparation and makes recommendations for needed witness preparation research.
Within-Patient Variability in Tacrolimus Blood Levels Predicts Kidney Graft Loss and Donor-Specific Antibody Development

Background Lack of adherence to immunosuppressive drugs is a risk factor for development of de novo donor-specific antibodies (dnDSA) and can contribute to antibody-mediated rejection and graft loss. Moreover, nonadherence is the main determinant of immunosuppressive drug level variability. High intrapatient variability of tacrolimus relates to a worse outcome in transplant recipients through unknown mechanisms. We hypothesized that a high within-patient variability of tacrolimus could increase the rate of dnDSA development and contribute to further death-censored graft loss (DCGL). Methods We included 310 adult renal transplants receiving twice-daily tacrolimus throughout their first posttransplant year, with (1) at least 3 blood trough levels available to calculate coefficient of variation (CV) from month 4 to 12, (2) graft survival longer than 1 year, and (3) absence of pretransplant DSA. The dnDSA were analyzed in sera at 1, 3, and 5 years and around 6 month before the last follow-up visit or graft loss by single-antigen beads. Results During the follow-up, 53 patients lost their graft excluding death. A total of 116 patients (37.4%) had a CV greater than 30% and 39 (12.6%) developed dnDSA. Coefficient of variation greater than 30% (hazards ratio, 2.613; 95% confidence interval, 1.361-5.016; P = 0.004) independently related to DCGL. Acute rejection, re-transplant and CV greater than 30% (hazards ratio, 2.925; 95% confidence interval, 1.473-5.807; P = 0.002) were the only variables related to dnDSA development by Cox regression analysis. Conclusions Tacrolimus level variability is a strong risk factor for dnDSA development and DCGL. Variability must be added to the current monitoring of kidney transplant recipients due to its relationship with adherence and to graft outcome.
Relationship of psychosis to aggression, apathy and function in dementia

Psychosis has been associated with aggression in dementia, but the nature of this relationship has been unclear. There has been very little research into the relations between apathy and functional status to psychosis in dementia. The purpose of this study is to investigate the relationship between psychosis and aggression, apathy, and functional status in outpatients with dementia.
Percutaneous Nephrolithotomy During Early Pregnancy in Urgent Situations: Is It Feasible and Safe?

PURPOSE Urolithiasis during pregnancy poses risks for mother and the fetus with specific challenges in diagnosis and management. We report our experience with urgent percutaneous nephrolithotomy (PCNL) in seven pregnant patients with symptomatic renal stone in early pregnancy. MATERIALS AND METHODS Seven pregnant patients with symptomatic renal stones were reviewed. The technique comprised PCNL with complete access under guide of ultrasonography in prone position under general anesthesiausing pneumatic lithoclast for stone fragmentation. RESULTS There was no significant residual fragment of stone in the operated kidneys. The patients discharged without complications and delivered their babies healthy. CONCLUSION PCNL should not be considered as the first therapeutic method in the first trimester of pregnancy, unless in urgent situations such as symptomatic renal pelvic stone with moderate to severe hydronephrosis in patients who do not tolerate or are complicated by nephrostomy or internal stent. However, this procedure could be technically demanding and should be done in centers with enough experience and equipment in percutaneousnephrolithotomy.
The expression of vesicular glutamate transporters VGLUT1 and VGLUT2 in neurochemically defined axonal populations in the rat spinal cord with emphasis on the dorsal horn

Two vesicular glutamate transporters, VGLUT1 and VGLUT2, have recently been identified, and it has been reported that they are expressed by largely nonoverlapping populations of glutamatergic neurons in the brain. We have used immunocytochemistry with antibodies against both transporters, together with markers for various populations of spinal neurons, in an attempt to identify glutamatergic interneurons in the dorsal horn of the mid‐lumbar spinal cord of the rat. The great majority (94–100%) of nonprimary axonal boutons that contained somatostatin, substance P or neurotensin, as well as 85% of those that contained enkephalin, were VGLUT2‐immunoreactive, which suggests that most dorsal horn neurons that synthesize these peptides are glutamatergic. In support of this, we found that most somatostatin‐ and enkephalin‐containing boutons (including somatostatin‐immunoreactive boutons that lacked calcitonin gene‐related peptide and were therefore probably derived from local interneurons) formed synapses at which AMPA receptors were present.
MAGED4 – expression in renal cell carcinoma and identification of an HLA-A*25-restricted MHC class I ligand from solid tumor tissue

MAGE derived HLA ligands have repeatedly been shown to elicit T-cell responses against tumor cells. In renal cell carcinoma (RCC), however, only few T-cell epitopes from cancer testis antigens have been described. To identify potential candidates, we applied a combined approach of microarray/qPCR expression analysis and sequencing of HLA ligands from RCC by mass spectrometry. We analyzed the expression of 21 MAGE genes in 10 RCC samples and 2 glioblastoma samples and could identify the first MHC class I ligand NIGDEALIGRW from MAGED4 presented by HLA-A*25 on RCC solid tumor tissue. MAGED4 was expressed in 30% of RCC and both glioblastoma samples. Among the other MAGE family members only MAGEB2 and -C1 and the broadly expressed MAGED1, -D2, -F1, and -H1 were expressed in RCC. Ligands from MAGED4 could thus be interesting tumor-associated antigens in a subset of RCC, even though the identified ligand is presented by a rather rare allele.
Clinical significance of granuloma in Crohn's disease.

AIM Granuloma is considered the hallmark of microscopic diagnosis in Crohn's disease (CD), but granulomas can be detected in only 21-60% of CD patients. The aim of this study was to evaluate the frequency of granulomas by multiple endoscopic biopsies in patients with CD and to examine whether group of patients with or without granuloma exhibit a different clinical course. METHODS Fifty-six patients with newly diagnosed CD were included in the study. Jejunoscopy, enteroclysis and ileo-colonoscopy were performed in all patients. At least two biopsy specimens from each examined gastrointestinal segment were examined microscopically searching granuloma. The clinical course was followed in all patients, and extraintestinal manifestations as well as details of any immunosuppressive therapy and surgical intervention were noted. RESULTS Granuloma was found in 44.6% of the cases (25 patients). Patients with granuloma had higher activity parameters at the time of the biopsies. Extraintestinal manifestations were observed and surgical interventions were performed more often in the granuloma group. The need of immunosuppressive therapy was significantly more frequent in the patients with granuloma. Granuloma formation is more often seen in younger patients, and mainly in the severe, active penetrating disease. CONCLUSION The significantly higher frequency of surgical interventions and immunosuppressive therapy suggests that granuloma formation is associated with a more severe disease course during the first years of CD.
Water on Mars: Isotopic constraints on exchange between the atmosphere and surface

Using a new measurement of the D/H fractionation efficiency and new estimates of the water loss, we calculate that Mars has the equivalent of a ∼9 m global water layer in a reservoir that exchanges with the atmosphere. The measured D/H enrichment is about 5 times the terrestrial value, but without exchange, the atmosphere converges on an enrichment of 50 in about 0.5 Ma. Due to the large buffering reservoir and the rapid loss rate (10−3 pr‐µm yr−1), the small atmospheric reservoir, averaging 10 pr‐µm, is unlikely to be in continuous isotopic equilibrium with the full 9 m exchangeable reservoir. Instead, it presumably equilibrates during periods of high obliquity; the atmospheric D/H ratio is expected to be enriched in between such periods. If isotopic exchange with a small (4 mm global layer) reservoir occurs under current conditions, it possible for the atmospheric D/H ratio to be within 10% of its long term equilibrium.
Distinct Contributions of Autophagy Receptors in Measles Virus Replication

Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO2 and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.
Long-Term Memory for Spatial and Temporal Mental Models Includes Construction Processes and Model Structure

There is a strong case that people construct and manipulate mental models in working memory but relatively little evidence that mental models are preserved in long-term memory. Instead people may remember an episodic construction trace: a record of the operations used to construct a mental model (Payne, 1993). Experiment 1 investigated memory for determinate spatial descriptions (which describe a single configuration of objects) and indeterminate spatial descriptions (which describe two equally plausible configurations). Recognition performance was impaired when the overlap between the episodic construction trace of a description at learning and at test was disrupted by reordering the sentences within a description. Participants were better at remembering the gist of determinate descriptions than that of indeterminate descriptions. For indeterminate descriptions, provided differences in gist recognition were controlled, participants showed better memory for the original description. Experiment 2 showed a similar pattern of results with temporal descriptions. A third experiment manipulated the similarity between foils in the recognition test and the original descriptions to provide further evidence for both episodic construction trace and remembered mental models. In combination, these results favour a hybrid account of memory for mental models, which includes information about both construction processes and model structure.