Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic value of C-reactive protein in HIV-infected patients with Pneumocystis jirovecii pneumonia

Summary C-reactive protein (CRP) is a sensitive marker of inflammation and tissue damage. We aimed to describe CRP responses in HIV-infected patients presenting with Pneumocystis pneumonia (PCP), bacterial pneumonia (BP) and pulmonary tuberculosis (TB) and, in patients with PCP, to identify if elevated CRP has prognostic significance. Data obtained by case-note review of consecutive HIV-infected adults with acute respiratory episodes included admission CRP (elevated >5 mg/L), haemoglobin, white blood count, CD4 count and partial pressure of oxygen in the blood (PaO2), presence of pulmonary co-pathology/intercurrent infection and outcome (survival). Median (range) CRP in patients with BP = 120 mg/L (<5–620 mg/L), TB = 44 mg/L (<5–256.3 mg/L) and PCP = 35 mg/L (<5–254 mg/L). CRP was elevated in 93/103 (90.3%) patients with PCP; six patients died; and all had an elevated CRP. PaO2 and CRP values were associated as follows: average CRP levels declined by 10% (95% confidence interval [CI] 0.20%) per kPa increase in PaO2 = 0.002. Factors associated with death were higher CRP, odds ratio (OR) (95% CI) = 5.30 (1.61 to 17.51) per 100 mg/L increase, P = 0.006 and haemoglobin, OR (95% CI) = 0.52 (0.29 to 0.93) per g/dL, P = 0.033. CRP is elevated in the majority of HIV-infected patients with PCP, BP and TB. Admission CRP measurement lacks specificity, but in PCP elevations of CRP are associated with disease severity (PaO2) and poor outcome and might be used prognostically, together with other mortality risk factors; further prospective evaluation is needed.
Short term exposure to air pollution and stroke: systematic review and meta-analysis

Objective To review the evidence for the short term association between air pollution and stroke. Design Systematic review and meta-analysis of observational studies Data sources Medline, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and Web of Science searched to January 2014 with no language restrictions. Eligibility criteria Studies investigating the short term associations (up to lag of seven days) between daily increases in gaseous pollutants (carbon monoxide, sulphur dioxide, nitrogen dioxide, ozone) and particulate matter (<2.5 µm or <10 µm diameter (PM2.5 and PM10)), and admission to hospital for stroke or mortality. Main outcome measures Admission to hospital and mortality from stroke. Results From 2748 articles, 238 were reviewed in depth with 103 satisfying our inclusion criteria and 94 contributing to our meta-estimates. This provided a total of 6.2 million events across 28 countries. Admission to hospital for stroke or mortality from stroke was associated with an increase in concentrations of carbon monoxide (relative risk 1.015 per 1 ppm, 95% confidence interval 1.004 to 1.026), sulphur dioxide (1.019 per 10 ppb, 1.011 to 1.027), and nitrogen dioxide (1.014 per 10 ppb, 1.009 to 1.019). Increases in PM2.5 and PM10 concentration were also associated with admission and mortality (1.011 per 10 μg/m3 (1.011 to 1.012) and 1.003 per 10 µg/m3 (1.002 to 1.004), respectively). The weakest association was seen with ozone (1.001 per 10 ppb, 1.000 to 1.002). Strongest associations were observed on the day of exposure with more persistent effects observed for PM2·5. Conclusion Gaseous and particulate air pollutants have a marked and close temporal association with admissions to hospital for stroke or mortality from stroke. Public and environmental health policies to reduce air pollution could reduce the burden of stroke. Systematic review registration PROSPERO-CRD42014009225.
Activation and promotion of adipose stem cells by tumour necrosis factor‐alpha preconditioning for bone regeneration

There is a major medical need for developing novel and effective approaches for repairing non‐union and critical‐sized bone defects. Although the mechanisms remain to be determined, it is known that inflammation plays a crucial role in initiating bone repair and regeneration. This study investigated the effect of short‐term (3 days) preconditioning with tumor necrosis factor‐alpha (TNF‐α) on proliferation, mobilization, and differentiation of adipose tissue‐derived mesenchymal stem cells (ASCs). We demonstrated that TNF‐α pre‐conditioning increased proliferation, mobilization, and osteogenic differentiation of ASCs and up‐regulated bone morphogenetic protein‐2 (BMP‐2) protein level. BMP‐2 silencing by siRNA partially inhibited osteogenic differentiation of ASCs induced by TNF‐α; BMP‐2 pre‐conditioning also significantly increased osteogenic differentiation of ASCs but the effects were significantly smaller than those observed for TNF‐α preconditioning. Furthermore, TNF‐α treatment promoted extracellular‐signal‐regulated kinases(Erk)1/2 and p38 mitogen‐activated protein kinase (MAPK) signaling pathways, but only Erk1/2 inhibition reduced the BMP‐2 levels and osteogenic differentiation induced by TNF‐α preconditioning. Together, these results support the hypothesis that inflammation contributes to bone regeneration by promoting proliferation, mobilization, and osteogenic differentiation of ASCs; 3 days of TNF‐α preconditioning, mimicking the short boost of inflammation normally occurring after bone injury, might serve as a feasible approach for directing stem cells into osteogenic differentiation. J. Cell. Physiol. 9999: XX–XX, 2013. © 2013 Wiley Periodicals, Inc. J. Cell. Physiol. 228: 1737–1744, 2013. © 2013 Wiley Periodicals, Inc.
Musculoskeletal architecture of the prey capture apparatus in salamandrid newts with multiphasic lifestyle: does anatomy change during the seasonal habitat switches?

Some newt species change seasonally between an aquatic and a terrestrial life as adults, and are therefore repeatedly faced with different physical circumstances that affect a wide range of functions of the organism. For example, it has been observed that seasonally habitat‐changing newts display notable changes in skin texture and tail fin anatomy, allowing one to distinguish an aquatic and a terrestrial morphotype. One of the main functional challenges is the switch between efficient aquatic and terrestrial prey capture modes. Recent studies have shown that newts adapt quickly by showing a high degree of behavioral flexibility, using suction feeding in their aquatic stage and tongue prehension in their terrestrial stage. As suction feeding and tongue prehension place different functional demands on the prey capture apparatus, this behavioral flexibility may clearly benefit from an associated morphological plasticity. In this study, we provide a detailed morphological analysis of the musculoskeletal system of the prey capture apparatus in the two multiphasic newt species Ichthyosaura alpestris and Lissotriton vulgaris by using histological sections and micro‐computed tomography. We then test for quantitative changes of the hyobranchial musculoskeletal system between aquatic and terrestrial morphotypes, The descriptive morphology of the cranio‐cervical musculoskeletal system provides new insights on form and function of the prey capture apparatus in newts, and the quantitative approach shows hypertrophy of the hyolingual musculoskeletal system in the terrestrial morphotype of L. vulgaris but hypertrophy in the aquatic morphotype of I. alpestris. It was therefore concluded that the seasonal habitat shifts are accompanied by a species‐dependent muscular plasticity of which the potential effect on multiphasic feeding performance in newts remains unclear.
Pharmacokinetics of Abacavir and its Anabolite Carbovir Triphosphate without and with Darunavir/ Ritonavir or Raltegravir in HIV-Infected Subjects

Background Here, we aimed to investigate the pharmacokinetics of abacavir and carbovir triphosphate (CBV-TP) with darunavir/ritonavir 900/100 mg once daily or raltegravir 400 mg twice daily. Methods HIV-infected subjects on abacavir (600 mg once daily) underwent steady-state pharmacokinetic assessments without and with darunavir/ritonavir or raltegravir. Within-subject changes in plasma and intracellular pharmacokinetic parameters were evaluated by geometric mean ratios (GMRs) and 90% CIs. Results A total of 19 patients completed the study. With darunavir/ritonavir (versus abacavir alone), abacavir GMRs (90% CI) were 0.73 (0.66, 0.80), 0.62 (0.50, 0.77) and 0.78 (0.69, 0.87) for area under the curve (AUC), trough concentration (Ctrough) and maximum concentration (Cmax), respectively. With raltegravir, they were 1.03 (0.97, 1.10), 0.83 (0.62, 1.11) and 1.06 (0.95, 1.18), respectively. Intracellular CBV-TP GMRs (90% CI) were 0.88 (0.72, 1.07), 0.68 (0.48, 0.95) and 0.98 (0.79, 1.23) for AUC, Ctrough and Cmax, respectively, with darunavir/ritonavir, and 0.96 (0.76, 1.20), 0.57 (0.33, 1.00) and 1.07 (0.85, 1.35), respectively, with raltegravir. Conclusions There was a 27% decrease in abacavir plasma exposure with darunavir/ritonavir and no changes with raltegravir. CBV-TP Ctrough was significantly decreased with darunavir/ritonavir (32%) and showed a high inter-individual variability with raltegravir.
Changing management of gallstone-related disease in pregnancy – a retrospective cohort analysis

Abstract Objectives: Gallstone-related disease is the second most common non-obstetric cause, following appendicitis, for acute abdomen in pregnancy. This study aimed to investigate treatment strategies, changes over time and outcome. Materials and methods: All consecutive patients with symptomatic gallstone-related disease during pregnancy admitted to Skane University hospital in Lund and Malmö 2001–2015 were analysed retrospectively. Information regarding the patient, pregnancy and fetus/child was recorded. The material was analysed by dividing it into two equal time periods and by comparing conservative management and surgical intervention. Results: We included 96 patients with 97 pregnancies. The age was 30 (26–34) years and BMI 28 (24–31). Median length of pregnancy at first admission was 23 (13–31) weeks. The three most common diagnoses were biliary colic (n = 63), cholecystitis (n = 22) and acute pancreatitis (n = 16). Conservative treatment was practiced in 62 (64%) patients and intervention in 35 (36%). Conservatively treated patients were admitted later during pregnancy (week 26 (20–33) versus 17 (10–22), p < . 001). Surgically treated patients had a longer total length of stay (all admissions) than conservatively treated patients (p = .001), less readmissions (p = .001) and equal birth outcome. Surgical intervention was more common in the later time period (48% versus 22%, p = .011). Of the conservatively treated patients, 56% were subjected to surgical intervention within 2 years after delivery. Conclusions: We found that intervention was more common in the later time period, with good results concerning safety, and less readmissions. A majority of the conservatively treated patients had surgical intervention within two years after delivery. Our results support surgical intervention in pregnancy.
Combination Therapy with Amantadine, Oseltamivir and Ribavirin for Influenza a Infection: Safety and Pharmacokinetics

Background Antiviral resistance among influenza A viruses is associated with high morbidity and mortality in immunocompromised hosts. However, treatment strategies for drug-resistant influenza A are not established. A triple-combination antiviral drug (TCAD) regimen consisting of amantadine (AMT), oseltamivir (OSL) and ribavirin (RBV) demonstrated good efficacy in an animal model. Methods We first analysed the pharmacokinetics (PKs) of TCAD therapy in healthy volunteers. We then performed a pilot study of TCAD therapy in patients undergoing chemotherapy or haematopoietic cell transplantation. AMT (75 mg), OSL (50 mg) and RBV (200 mg) were administered three times a day for 10 days. The safety and PKs of TCAD therapy were monitored. Results The PKs of TCAD therapy in healthy volunteers was shown to be similar to the PKs of each drug individually from a single dose. In the pilot study, six immunocompromised patients received TCAD therapy and one patient received OSL monotherapy. All but one patient completed 10 days of TCAD therapy without side effects; one patient receiving TCAD was withdrawn from the study because of respiratory failure and ultimately recovered. Viral load was decreased after TCAD therapy, despite the presence of either AMT- or OSL-resistant virus in two cases. One patient with 2009 influenza A/ H1N1 receiving OSL monotherapy developed confirmed OSL resistance during treatment. Conclusions TCAD therapy had similar PKs to each individual antiviral during monotherapy following a single dose and can be administered safely in immunocompromised patients.
Evaluation of Luminex xTAG Gastrointestinal Pathogen Panel Assay for Detection of Multiple Diarrheal Pathogens in Fecal Samples in Vietnam

ABSTRACT Diarrheal disease is a complex syndrome that remains a leading cause of global childhood morbidity and mortality. The diagnosis of enteric pathogens in a timely and precise manner is important for making treatment decisions and informing public health policy, but accurate diagnosis is a major challenge in industrializing countries. Multiplex molecular diagnostic techniques may represent a significant improvement over classical approaches. We evaluated the Luminex xTAG gastrointestinal pathogen panel (GPP) assay for the detection of common enteric bacterial and viral pathogens in Vietnam. Microbiological culture and real-time PCR were used as gold standards. The tests were performed on 479 stool samples collected from people admitted to the hospital for diarrheal disease throughout Vietnam. Sensitivity and specificity were calculated for the xTAG GPP for the seven principal diarrheal etiologies. The sensitivity and specificity for the xTAG GPP were >88% for Shigella spp. , Campylobacter spp. , rotavirus, norovirus genotype 1/2 (GI/GII), and adenovirus compared to those of microbiological culture and/or real-time PCR. However, the specificity was low (∼60%) for Salmonella species. Additionally, a number of important pathogens that are not identified in routine hospital procedures in this setting, such as Cryptosporidium spp. and Clostridium difficile, were detected with the GPP. The use of the Luminex xTAG GPP for the detection of enteric pathogens in settings, like Vietnam, would dramatically improve the diagnostic accuracy and capacity of hospital laboratories, allowing for timely and appropriate therapy decisions and a wider understanding of the epidemiology of pathogens associated with severe diarrheal disease in low-resource settings.
Sialoadhesin-Positive Macrophages Bind Regulatory T Cells, Negatively Controlling Their Expansion and Autoimmune Disease Progression1

An important regulatory suppressive function in autoimmune and other inflammatory processes has been ascribed to CD4+Foxp3+ regulatory T cells (Tregs), which requires direct cell-cell communication between Tregs, effector T cells, and APCs. However, the molecular basis for these interactions has not yet been clarified. We show here that sialoadhesin (Sn), the prototype of the siglec family of sialic acid-binding transmembrane proteins, expressed by resident and activated tissue-infiltrating macrophages, directly binds to Tregs, negatively regulating their expansion in an animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In this model, macrophages infiltrate the CNS exhibiting tissue-destructing and demyelinating activity, leading to MS-like symptoms. We show here that severity of EAE symptoms is reduced in Sn knockout (KO) mice compared with wild-type littermates due to an up-regulation of CD4+Foxp3+ Treg lymphocytes. Through the use of a Sn fusion protein, Tregs were shown to express substantial amounts of Sn ligand on their cell surface, and direct interaction of Sn+ macrophages with Tregs specifically inhibited Treg but not effector T lymphocyte proliferation. Conversely, blocking of Sn on macrophages by Sn-specific Abs resulted in elevated proliferation of Tregs. Data indicate that Sn+ macrophages regulate Treg homeostasis which subsequently influences EAE progression. We propose a new direct cell-cell interaction-based mechanism regulating the expansion of the Tregs during the immune response, representing a “dialogue” between Sn+ macrophages and Sn-accessible sialic acid residues on Treg lymphocytes.
ACTN3 Genotype, Athletic Status, and Life Course Physical Capability: Meta-Analysis of the Published Literature and Findings from Nine Studies

The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, although not consistently. Our objective was to conduct a meta‐analysis of the published literature on athletic status and investigate its associations with physical capability in several new population‐based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For life course physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research program, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (P = 0.09, n = 7,672 in males; P = 0.90, n = 7,839 in females), standing balance, timed get up and go, or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population. Hum Mutat 32:1–11, 2011. © 2011 Wiley‐Liss, Inc.
Exploring the Relationship Between Gratitude and Family Satisfaction Among College Students

WILLIAMS, SR., MICHAEL A. , Ph.D., August 2012, Counselor Education Exploring the Relationship Between Gratitude and Family Satisfaction Among College Students (162 pp.) Director of Dissertation: Thomas E. Davis The purpose of this study was to explore the relationship between gratitude and family satisfaction among college students, to investigate if the strength of the relationship between the two constructs were significantly different when the gender of the college student was taken into account and to identify some potential trends in the way that family satisfaction and gratitude were both conceptualized and expressed. A sample of 133 college students completed a web-based survey which included questions pertaining to demographics, the Gratitude Questionaire-6 (GQ-6; McCullough et al., 2002), the Family Satisfaction Survey (FSS; Olson, 2010) and a series of openended survey questions designed to elicit detail responses regarding the views of the respondents as they pertained to the constructs. Data collected from the GQ6 and the FSS were analyzed using a Pearson’s Correlation. A Regression analysis was conducted in order to examine additional data collected via the open-ended questions. Results indicated that a significantly positive relationship exists between gratitude and family satisfaction among college students. However, there is no significant difference in the relationship when examined along the lines of gender. This research supports the view that positive emotions are tied to desired outcomes such as family satisfaction. The research also encourages research into the use 4 of gratitude based interventions with individuals as well as families particularly those with members who are college students. Additionally, this research is relevant to those who seek to train professionals who serve families and college students including but not limited to counselor educators. Approved: _____________________________________________________________ Thomas E. Davis Professor of Counseling and Higher Education
Explaining Function with Anatomy: Language Lateralization and Corpus Callosum Size

The anatomy of the corpus callosum (CC) has been advocated as a potential marker for functional lateralization because its size is supposedly proportional to the number of fibers connecting the hemispheres. Previous morphometric studies of this relationship have compared CC size in groups of subjects who are more or less likely to show differences in their lateralization (e.g., left vs right handers). The findings, however, have been inconsistent, and to our knowledge, no previous study has directly compared CC size with lateralization assessed by functional imaging data. We therefore combined anatomical measurements of CC size with left versus right hemisphere language activation in 74 normal subjects. After controlling for perceptual and motor output effects, as well as for global white-matter volume, handedness, gender and age, we found that subjects who had a larger CC showed more left lateralization for language in posterior temporal and inferior frontal regions. Examination of these effects revealed that, as CC size increased, stronger lateralization resulted from more left hemisphere activation in both regions as well as reduced right hemisphere activation in the posterior temporal region. Our observations provide the first clear evidence in normal subjects that the midsagittal surface area of the CC contributes to the degree to which language is functionally lateralized. We discuss the complex interhemispheric processes that might underlie this effect.
Galectin-2 Induces a Proinflammatory, Anti-Arteriogenic Phenotype in Monocytes and Macrophages

Galectin-2 is a monocyte-expressed carbohydrate-binding lectin, for which increased expression is genetically determined and associated with decreased collateral arteriogenesis in obstructive coronary artery disease patients. The inhibiting effect of galectin-2 on arteriogenesis was confirmed in vivo, but the mechanism is largely unknown. In this study we aimed to explore the effects of galectin-2 on monocyte/macrophage phenotype in vitro and vivo, and to identify the receptor by which galectin-2 exerts these effects. We now show that the binding of galectin-2 to different circulating human monocyte subsets is dependent on monocyte surface expression levels of CD14. The high affinity binding is blocked by an anti-CD14 antibody but not by carbohydrates, indicating a specific protein-protein interaction. Galectin-2 binding to human monocytes modulated their transcriptome by inducing proinflammatory cytokines and inhibiting pro-arteriogenic factors, while attenuating monocyte migration. Using specific knock-out mice, we show that galectin-2 acts through the CD14/toll-like receptor (TLR)-4 pathway. Furthermore, galectin-2 skews human macrophages to a M1-like proinflammatory phenotype, characterized by a reduced motility and expression of an anti-arteriogenic cytokine/growth factor repertoire. This is accompanied by a switch in surface protein expression to CD40-high and CD206-low (M1). In a murine model we show that galectin-2 administration, known to attenuate arteriogenesis, leads to increased numbers of CD40-positive (M1) and reduced numbers of CD206-positive (M2) macrophages surrounding actively remodeling collateral arteries. In conclusion galectin-2 is the first endogenous CD14/TLR4 ligand that induces a proinflammatory, non-arteriogenic phenotype in monocytes/macrophages. Interference with CD14-Galectin-2 interaction may provide a new intervention strategy to stimulate growth of collateral arteries in genetically compromised cardiovascular patients.