Miracle-dz/UniFAR-FTUs huggingface dataset:
Biology of cachexia.

About half of all cancer patients show a syndrome of cachexia, characterized by loss of adipose tissue and skeletal muscle mass. Such patients have a decreased survival time, compared with the survival time among patients without weight loss, and loss of total body protein leads to substantial impairment of respiratory muscle function. These changes cannot be fully explained by the accompanying anorexia, and nutritional supplementation alone is unable to reverse the wasting process. Despite a falling caloric intake, patients with cachexia frequently show an elevated resting energy expenditure as a result of increases in Cori cycle (i.e., catalytic conversion of lactic acid to glucose) activity, glucose and triglyceride-fatty acid cycling, and gluconeogenesis. A number of cytokines, including tumor necrosis factor-apha, interleukins 1 and 6, interferon gamma, and leukemia-inhibitory factor, have been proposed as mediators of the cachectic process. However, the results of a number of clinical and laboratory studies suggest that the action of the cytokines alone is unable to explain the complex mechanism of wasting in cancer cachexia. In addition, cachexia has been observed in some xenograft models even without a cytokine involvement, suggesting that other factors may be involved. These probably include catabolic factors, which act directly on skeletal muscle and adipose tissue and the presence of which has been associated with the clinical development of cachexia. A polyunsaturated fatty acid, eicosapentaenoic acid, attenuates the action of such catabolic factors and has been shown to stabilize the process of wasting and resting energy expenditure in patients with pancreatic cancer. Such a pharmacologic approach may provide new insights into the treatment of cachexia.
Green tea polyphenol (–)‐epigallocatechin‐3‐gallate induces neurorescue of long‐term serum‐deprived PC12 cells and promotes neurite outgrowth

Our previous studies have shown that the green tea polyphenol (–)‐epigallocatechin‐3‐gallate (EGCG) prevents neuronal cell death caused by several neurotoxins. The present study sought to determine the neuroprotective effect of EGCG when it is administered after the induction of cell damage (‘neurorescue’). In an attempt to imitate a progressive mode of death, PC12 cells were initially subjected to serum‐starvation conditions for a period of 1 or 3 days before administration of EGCG (0.1–10 µm) for up to 3 days. In spite of the high percentage of cell death, single or repetitive administration of EGCG (1 µm) significantly attenuated cell death. The neurorescue effect of EGCG was abolished by pre‐treatment with the protein kinase C inhibitor GF109203X (2.5 µm), suggesting the involvement of the protein kinase C pathway in neurorescue by the drug. This is consistent with the rapid (15 min) translocation of the protein kinase C alpha isoform to the cell membrane in response to EGCG. The correlative neurite outgrowth activity of EGCG on PC12 cells may also contribute to its neurorescue effect. The present findings suggest that EGCG may have a positive impact on aging and neurodegenerative diseases to retard or perhaps even reverse the accelerated rate of neuronal degeneration.
Has TRISS become an anachronism? A comparison of mortality between the National Trauma Data Bank and Major Trauma Outcome Study databases

BACKGROUND The Trauma and Injury Severity Score (TRISS) has been the approach to trauma outcome prediction during the past 20 years and has been adopted by many commercial registries. Unfortunately, its survival predictions are based upon coefficients that were derived from a data set collected in the 1980s and updated only once using a data set collected in the early 1990s. We hypothesized that the improvements in trauma care during the past 20 years would lead to improved survival in a large database, thus making the TRISS biased. METHODS The TRISSs from the Pennsylvania statewide trauma registry (Collector, Digital Innovations) for the years 1990 to 2010. Observed-to-expected mortality ratios for each year of the study were calculated by taking the ratio of actual deaths (observed deaths, O) to the summation of the probability of mortality predicted by the TRISS taken over all patients (expected deaths, E). For reference, O/E ratio should approach 1 if the TRISS is well calibrated (i.e., has predictive accuracy). RESULTS There were 408,489 patients with complete data sufficient to calculate the TRISSs. There was a significant trend toward improved outcome (i.e., decreasing O/E ratio; nonparametric test of trend, p < 0.001) over time in both the total population and the blunt trauma subpopulation. In the penetrating trauma population, there was a trend toward improved outcome (decreasing O/E ratio), but it did not quite reach significance (nonparametric test of trend p = 0.073). CONCLUSION There is a steady trend toward improved O/E survival in the Pennsylvania database with each passing year, suggesting that the TRISS is drifting out of calibration. It is likely that improvements in care account for these changes. For the TRISS to remain an accurate outcome prediction model, new coefficients would need to be calculated periodically to keep up with trends in trauma care. This requirement for occasional updating is likely to be a requirement of any trauma prediction model, but because many other deficiencies in the TRISS have been reported, we think that rather than updating the TRISS, it would be more productive to replace the TRISS with a modern statistical model. LEVEL OF EVIDENCE Prognostic study, level II.
Availability of healthy snack foods and beverages in stores near high-income urban, low-income urban, and rural elementary and middle schools in Oregon.

BACKGROUND Food stores near schools are an important source of snacks for children. However, few studies have assessed availability of healthy snacks in these settings. The aim of this study was to assess availability of healthy snack foods and beverages in stores near schools and examine how availability of healthy items varied by poverty level of the school and rural-urban location. METHODS Food stores were selected based on their proximity to elementary/middle schools in three categories: high-income urban, low-income urban, and rural. Audits were conducted within the stores to assess the presence or absence of 48 items in single-serving sizes, including healthy beverages, healthy snacks, fresh fruits, and fresh vegetables. RESULTS Overall, availability of healthy snack foods and beverages was low in all stores. However, there was significant cross-site variability in availability of several snack and fruit items, with stores near high-income urban schools having higher availability, compared to stores near low-income urban and/or rural schools. Stores near rural schools generally had the lowest availability, although several fruits were found more often in rural stores than in urban stores. There were no significant differences in availability of healthy beverages and fresh vegetables across sites. CONCLUSIONS Availability of healthy snack foods and beverages was limited in stores near schools, but these limitations were more severe in stores proximal to rural and low-income schools. Given that children frequent these stores to purchase snacks, efforts to increase the availability of healthy products, especially in stores near rural and low-income schools, should be a priority.
COMPARATIVE AND THEORETICAL APPROACHES TO STUDYING SEXUAL SELECTION IN PRIMATES

Primates exhibit amazing variation in traits that are likely to have arisen through sexual selection. Many of these traits play a role in visual or chemical communication. The striking countenance of a dominant male mandrill serves as a classic example [Setchell]. Scent marking in callitrichids is another form of communication that may be sexually selected [Heymann], while dichromatism is a complicated phenomenon that is likely to be influenced by many factors, including sexual selection [Gerald]. Other sexually-selected traits are behavioral, including female intrasexual competition for mates [Saltzman; Vervaecke et al.; Heymann], infanticide by males [Crockett] or females [Digby, 1995; Saltzman], and cryptic female choice [Reeder]. Finally, sexual selection itself may be influenced by the competitive regime, as mediated, for example, by demographic factors [Strier; Watson et al.]. Primatologists have made great strides in understanding sexual selection in primates. The chapters in this book, which I summarize here, highlight many of these exciting advances, while also illustrating the shift from descriptive accounts of primate biology to tests of hypotheses that have arisen from advances in mainstream behavioral ecology [Shahnoor & Jones]. One chapter in this volume, for example, investigates the potential for applying new models of reproductive skew to understand patterns of sexual selection in primates [Hager]. Skew models are one of the most influential conceptual frameworks to emerge in the last decade of behavioral ecology research [Clutton-Brock, 1998; Reeve et al., 1998; Johnstone, 2000]. Figure 1 shows the number of citations for “reproductive skew” in a search of ISI’s Web of Science for the years 1994 to 2001. When “primate” is included as an additional search term, however, no hits are obtained, illustrating the lack of attention by primatologists to this conceptual framework. Similarly, searching for the phrase “reproductive skew” produced only two
Long-term posttraumatic stress symptoms vary inversely with early opiate dosing in children recovering from serious burns: Effects durable at 4 years

BACKGROUND Children surviving serious burns are at risk for developing posttraumatic stress disorder (PTSD) as a function both of the injury and of its treatment. Short-term studies in such children have demonstrated reduced PTSD symptoms with intensive early pain control. However, the long-term impact of early pain control strategies on posttraumatic stress symptoms in children recovering from serious burn injuries has not been examined. METHODS This was a retrospective review of a multiple time point data collection involving a cohort of 147 infants, children, and teenagers with 4 years of follow-up after serious burns conducted at 4 pediatric burn centers to examine the impact of early opiate dosing on long-term posttraumatic stress symptoms. The main outcome measure was the nine-item Short Form Child Stress Disorders Checklist, which is an established and validated assessment. The impact of total opiate dosing during the first 7 days on these scores was assessed. RESULTS Subjects had an average age of 11 years and average injury size of 22% total body surface area burned (%TBS). The correlation between opiate units (OUs) and %TBS was 0.46 at baseline, OU increasing with increasing %TBS. OUs were strongly predictive of Child Stress Disorders Checklist scores up to 4 years, with higher OU (10 units vs. 6 and 2 units) remaining constantly different up to 4 years in predicting lower stress scores for both smaller and larger burns. CONCLUSION Early opiate management of pain associated with acute burn wounds and burn treatment predicts the development and resolution rate of PTSD symptoms in a large multicenter sample of children hospitalized for serious burns. The effect seems to be dose related and durable at least up to 4 years in a range of burn sizes. LEVEL OF EVIDENCE Prognostic/epidemiologic study, level II.
A survey of mangiferin and hydroxycinnamic acid ester accumulation in coffee (Coffea) leaves: biological implications and uses.

BACKGROUND AND AIMS The phenolic composition of Coffea leaves has barely been studied, and therefore this study conducts the first detailed survey, focusing on mangiferin and hydroxycinnamic acid esters (HCEs). METHODS Using HPLC, including a new technique allowing quantification of feruloylquinic acid together with mangiferin, and histochemical methods, mangiferin content and tissue localization were compared in leaves and fruits of C. pseudozanguebariae, C. arabica and C. canephora. The HCE and mangiferin content of leaves was evaluated for 23 species native to Africa or Madagascar. Using various statistical methods, data were assessed in relation to distribution, ecology, phylogeny and use. KEY RESULTS Seven of the 23 species accumulated mangiferin in their leaves. Mangiferin leaf-accumulating species also contain mangiferin in the fruits, but only in the outer (sporophytic) parts. In both leaves and fruit, mangiferin accumulation decreases with ageing. A relationship between mangiferin accumulation and UV levels is posited, owing to localization with photosynthetic tissues, and systematic distribution in high altitude clades and species with high altitude representatives. Analyses of mangiferin and HCE content showed that there are significant differences between species, and that samples can be grouped into species, with few exceptions. These data also provide independent support for various Coffea lineages, as proposed by molecular phylogenetic analyses. Sampling of the hybrids C. arabica and C. heterocalyx cf. indicates that mangiferin and HCE accumulation may be under independent parental influence. CONCLUSIONS This survey of the phenolic composition in Coffea leaves shows that mangiferin and HCE accumulation corresponds to lineage recognition and species delimitation, respectively. Knowledge of the spectrum of phenolic accumulation within species and populations could be of considerable significance for adaptation to specific environments. The potential health benefits of coffee-leaf tea, and beverages and masticatory products made from the fleshy parts of Coffea fruits, are supported by our phenolic quantification.
Flooding in Central Chile: Implications of Tides and Sea Level Increase in the 21st Century

Coastal floods have become a serious problem on a global scale, increasing in frequency or magnitude due to natural conditions, and exacerbated by socioeconomic factors. This investigation analyzes the role of tides and average sea levels on the development and intensity of flooding in the lower section of the Andalién River, located toward the southern extreme of the coast of central Chile and northeast of Concepción, the country’s second most populous city. Numerical simulation (1D) was used in five modeled scenarios to determine potential flooding areas, demonstrating the influence of tides in flooding processes as far away as 7.3 km from the river mouth, which is reinforced by the fact that 57% of flooding events occur during syzygies. Further, a climate change-induced sea level rise of 60 cm from current levels by the end of the 21st century would produce a 4% increase in flood-prone areas, with 17% of flooding affecting the current built-up area and 83% of floodplains and salt marshes. Efforts must be made to protect or conserve these latter areas in order to increase natural resilience, given the high costs of implementing structural measures to protect future residential areas.
Altered UDP-Glucuronosyltransferase and Sulfotransferase Expression and Function during Progressive Stages of Human Nonalcoholic Fatty Liver Disease

The UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) represent major phase II drug-metabolizing enzymes that are also responsible for maintaining cellular homeostasis by metabolism of several endogenous molecules. Perturbations in the expression or function of these enzymes can lead to metabolic disorders and improper management of xenobiotics and endobiotics. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver damage ranging from steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Because the liver plays a central role in the metabolism of xenobiotics, the purpose of the current study was to determine the effect of human NAFLD progression on the expression and function of UGTs and SULTs in normal, steatosis, NASH (fatty), and NASH (not fatty/cirrhosis) samples. We identified upregulation of UGT1A9, 2B10, and 3A1 and SULT1C4 mRNA in both stages of NASH, whereas UGT2A3, 2B15, and 2B28 and SULT1A1, 2B1, and 4A1 as well as 3′-phosphoadenosine-5′-phosphosulfate synthase 1 were increased in NASH (not fatty/cirrhosis) only. UGT1A9 and 1A6 and SULT1A1 and 2A1 protein levels were decreased in NASH; however, SULT1C4 was increased. Measurement of the glucuronidation and sulfonation of acetaminophen (APAP) revealed no alterations in glucuronidation; however, SULT activity was increased in steatosis compared with normal samples, but then decreased in NASH compared with steatosis. In conclusion, the expression of specific UGT and SULT isoforms appears to be differentially regulated, whereas sulfonation of APAP is disrupted during progression of NAFLD.
Individual Placement and Support in Sweden—A randomized controlled trial

Abstract Background: Currently there is no evidence on the effectiveness of Individual Placement and Support (IPS) in Sweden. Aims: To determine the effectiveness of IPS on vocational outcomes among people with severe mental illness (SMI) in a Swedish context. A secondary aim was to evaluate a community integration effect. Methods: A randomized controlled trial with a parallel design was used. Mental health outpatients with SMI were randomized to IPS or traditional vocational rehabilitation (TVR) services. The allocation status was assessor-blinded. The primary outcome was competitive employment. All vocational outcomes were collected continuously, and socio-demographic and clinical variables at baseline, 6 and 18 months. The trial is registered with ClinicalTrials.gov: NCT00960024. Results: One hundred and twenty participants were randomized. Eighty seven per cent were assessed after 6 months, and 73% after 18 months. IPS was more effective than TVR in terms of gaining employment at 18-month follow-up (46% vs. 11%; difference 36%, 95% CI 18–54), along with the amount of working hours and weeks, longer job tenure periods and income. Cox regression analysis showed that IPS participants gained employment five times quicker than those in TVR. Ninety per cent of the IPS participants became involved in work, internships or education, i.e. activities integrated in mainstream community settings, while 24% in the TVR group achieved this. Conclusions: IPS is effective in a Swedish context in terms of gaining employment and becoming integrated within the local community. The welfare system presented obstacles for gaining competitive employment directly and it was indicated that internships delayed time to first competitive employment.
Renal Interaction Between Itraconazole and Cimetidine

Renal drug interactions can result from competitive inhibition between drugs that undergo extensive renal tubular secretion by transporters such as P‐glycoprotein (P‐gp). The purpose of this study was to evaluate the effect of itraconazole, a known P‐gp inhibitor, on the renal tubular secretion of cimetidine in healthy volunteers who received intravenous cimetidine alone and following 3 days of oral itraconazole (400 mg/day) administration. Glomerular filtration rate (GFR) was measured continuously during each study visit using iothalamate clearance. Iothalamate, cimetidine, and itraconazole concentrations in plasma and urine were determined using high‐performance liquid chromatography/ultraviolet (HPLC/UV) methods. Renal tubular secretion (CLsec) of cimetidine was calculated as the difference between renal clearance (CLr) and GFR (CLioth) on days 1 and 5. Cimetidine pharmacokinetic estimates were obtained for total clearance (CLT), volume of distribution (Vd), elimination rate constant (Kel), area under the plasma concentration‐time curve (AUC0–240 min), and average plasma concentration (Cpave) before and after itraconazole administration. Plasma itraconazole concentrations following oral dosing ranged from 0.41 to 0.92 μg/mL. The cimetidine AUC0–240 min increased by 25% (p < 0.01) following itraconazole administration. The GFR and Vd remained unchanged, but significant reductions in CLT (655 vs. 486 mL/min, p < 0.001) and CLsec (410 vs. 311 mL/min, p = 0.001) were observed. The increased systemic exposure of cimetidine during coadministration with itraconazole was likely due to inhibition of P‐gp‐mediated renal tubular secretion. Further evaluation of renal P‐gp‐modulating drugs such as itraconazole that may alter the renal excretion of coadministered drugs is warranted.
Immunomodulatory drugs in multiple myeloma

Immunomodulatory drugs (IMiDs) are thalidomide analogues that retain the direct anticancer cytotoxic and immunological activity of their parent compound, but with a different toxicity profile. In vitro studies show that IMiDs have a more potent antitumour effect than thalidomide on multiple myeloma (MM) cell lines. This activity is mediated by multiple mechanisms: direct antiproliferative effect; inhibition of angiogenesis due to reduced IL-6 and vascular endothelial growth factor secretion; inhibition of cytokines production, especially TNF-α; and stimulation of T-cell activity. Two IMiDs, CC-5013 and CC-4047, have been tested in clinical trials in MM patients with progressive or refractory disease, and one trial is ongoing in newly diagnosed MM patients. Observed toxicities include thrombocytopoenia, neutropoenia and cardiovascular events, but no significant neurotoxicity has been reported. Partial responses (≥ 50% reduction in M-protein) ranged from 20 to 71% in different studies depending on the pretreatment status of the patients. The combination of IMiDs with dexamethasone may be beneficial.
Urokinase-type plasminogen activator inhibits efferocytosis of neutrophils.

RATIONALE Phagocytosis of apoptotic cells, also called efferocytosis, plays an essential role in the resolution of inflammation. Urokinase-type plasminogen activator (uPA) is a multifunctional protein that has been implicated in inflammatory conditions, including pneumonia and severe infection, which are often accompanied by the development of acute lung injury. However, the role of uPA in modulating efferocytosis of apoptotic neutrophils has not been defined. OBJECTIVES To characterize the role of uPA in regulation of efferocytosis and to delineate the underlying mechanisms involved in this process. METHODS In vitro and in vivo phagocytosis, immunoprecipitation, and Western blotting assays. MEASUREMENTS AND MAIN RESULTS The phagocytosis of apoptotic neutrophils by macrophages was significantly inhibited by uPA. Mutant uPA lacking the growth factor domain and catalytically inactive uPA had similar inhibitory effects on efferocytosis, as did wild-type uPA. In contrast, absence of the kringle domain abrogated the ability of uPA to diminish efferocytosis. Both the α(V)β₃ integrin and vitronectin seemed to be involved in the inhibition of efferocytosis by uPA. Incubation of macrophages with uPA also diminished activation of the small GTPase Rac-1, which normally occurs during ingestion of apoptotic neutrophils. Under in vivo conditions in the lungs, uPA decreased the uptake of apoptotic neutrophils by alveolar macrophages. CONCLUSIONS Our data demonstrate a novel role for uPA in which it is able to diminish the uptake of apoptotic neutrophils by macrophages under both in vitro and in vivo conditions.