Miracle-dz/UniFAR-FTUs huggingface dataset:
Prospective relation of C-reactive protein with type 2 diabetes: response to Han et al.

We read with great interest the article by Han et al., which was recently published in Diabetes Care (1). The authors studied the association between baseline levels of C-reactive protein (CRP) and the 6-year incidence of the metabolic syndrome and type 2 diabetes in Mexican subjects. They found an odds ratio (OR) of 4.1 (95% CI 2.1–8.0) for developing the metabolic syndrome and an OR of 5.4 (2.2–13.4) for incident type 2 diabetes among women in the highest compared with the lowest tertile of CRP. ORs were adjusted for age, smoking, physical activity, and alcohol intake. In men, no such association was found. Additional adjustment for BMI slightly lowered the ORs; adjustment for waist-to-hip …
Inducible Expression of the Cell Surface Heparan Sulfate Proteoglycan Syndecan-2 (Fibroglycan) on Human Activated Macrophages Can Regulate Fibroblast Growth Factor Action*

Monocyte/macrophages play important roles in regulating tissue growth and angiogenesis through the controlled release of heparin-binding growth factors such as fibroblast growth factor (FGF), vascular endothelial growth factor, and heparin binding epidermal growth factor. The action of these potent growth mediators is known to be regulated by adsorption to heparan sulfate proteoglycans (HSPGs) on the surface and within the extracellular matrix of other neighboring cells, which respectively promote or restrict interactions with their signal-transducing receptors on target cells. Here we report on the nature of HSPGs inducibly expressed on the surface of macrophages that confer these cells with the capacity to regulate endogenous growth factor activity. We reveal that activated human macrophages express only a single major 48-kDa cell surface HSPG, syndecan-2 (fibroglycan) as the result of de novo RNA and protein synthesis. In addition, we demonstrate this macrophage HSPG selectively binds the macrophage-derived growth factors FGF-2, vascular endothelial growth factor and heparin binding EGF and can present FGF-2 in a form that transactivates receptor-bearing BaF32 cells. These results define a novel and unique proteoglycan profile for macrophages and imply a key role for syndecan-2 in the delivery of sequestered growth factors by inflammatory macrophages for productive binding to their appropriate target cells in vivo.
Peplau’s Contributions to Psychiatric and Nursing Knowledge

Hildegard Peplau’s work formally began the development, basis and revolution of nursing knowledge for general nursing as well as for psychiatric mental health nursing. Her underlying philosophical assumptions and interpersonal relations theory not only emphasized the science of nursing that was empirically rooted and dominant from the time, but she illustrated how nursing as an art could equally contribute to the nursing knowledge, practice, and research that is so evident in nursing today. As a pioneer of nursing, Peplau helped to bridge the gap between theory and practice that continues to build on nursing’s knowledge base today. On the Canadian front, nurse leader, Cheryl Forchuk, continues to put it to the test.
Comparative study of the physiological roles of three peroxidases (NADH peroxidase, Alkyl hydroperoxide reductase and Thiol peroxidase) in oxidative stress response, survival inside macrophages and virulence of Enterococcus faecalis

The opportunistic pathogen Enterococcus faecalis is well equipped with peroxidatic activities. It harbours three loci encoding a NADH peroxidase, an alkyl hydroperoxide reductase and a protein (EF2932) belonging to the AhpC/TSA family. We present results demonstrating that ef2932 does encode a thiol peroxidase (Tpx) and show that it is part of the regulon of the hydrogen peroxide regulator HypR. Characterization of unmarked deletion mutants showed that all three peroxidases are important for the defence against externally provided H2O2. Exposure to internal generated H2O2 by aerobic growth on glycerol, lactose, galactose or ribose showed that Npr was absolutely required for aerobic growth on glycerol and optimal growth on the other substrates. Growth on glycerol was also dependent on Ahp. Addition of catalase restored growth of the mutants, and therefore, extracellular H2O2 concentrations have been determined. This showed that the time point of growth arrest of the Δnpr mutant correlated with the highest H2O2 concentration measured. Analysis of the survival of the different strains inside peritoneal macrophages revealed that Tpx was the most important antioxidant activity for protecting the cells against the hostile phagocyte environment. Finally, the Δtpx and the triple mutant showed attenuated virulence in a mouse peritonitis model.
Strategies to Improve Private-Well Water Quality: A North Carolina Perspective

Background: Evidence suggests that the 44.5 million U.S. residents drawing their drinking water from private wells face higher risks of waterborne contaminant exposure than those served by regulated community water supplies. Among U.S. states, North Carolina (N.C.) has the second-largest population relying on private wells, making it a useful microcosm to study challenges to maintaining private-well water quality. Objectives: This paper summarizes recommendations from a two-day summit to identify options to improve drinking-water quality for N.C. residents served by private wells. Methods: The Research Triangle Environmental Health Collaborative invited 111 participants with knowledge of private-well water challenges to attend the Summit. Participants worked in small groups that focused on specific aspects and reconvened in plenary sessions to formulate consensus recommendations. Discussion: Summit participants highlighted four main barriers to ensuring safe water for residents currently relying on private wells: (1) a database of private well locations is unavailable; (2) racial disparities have perpetuated reliance on private wells in some urbanized areas; (3) many private-well users lack information or resources to monitor and maintain their wells; and (4) private-well support programs are fragmented and lack sufficient resources. The Summit produced 10 consensus recommendations for ways to overcome these barriers. Conclusions: The Summit recommendations, if undertaken, could improve the health of North Carolinians facing elevated risks of exposure to waterborne contaminants because of their reliance on inadequately monitored and maintained private wells. Because many of the challenges in N.C. are common nationwide, these recommendations could serve as models for other states. https://doi.org/10.1289/EHP890
Rapid infancy weight gain and subsequent obesity: Systematic reviews and hopeful suggestions

In a systematic review, we identified 21 separate studies with data on the association between rapid infancy weight gain, up to age 2 y, and subsequent obesity risk. Uniformly all studies reported significant positive associations. We transformed the reported effect sizes to a standard infancy weight gain exposure, and found that further differences in study design accounted for much of the variation in risk. An accompanying paper by Melinda Yeung reminds us that there are benefits of postnatal catch‐up growth in certain populations, and suggests that genetic and nutritional factors could moderate the unhealthy translation of rapid infancy weight gain to visceral fat and insulin resistance. Further evidence is needed, and we will need to rigorously test the benefits and risks of any interventions. However, the concept of “healthy” rapid catch‐up infancy growth is an attractive prospect.
Oropharyngeal cancer – is it time to change management according to human papilloma virus status?

Purpose of reviewThere is currently strong evidence supporting human papilloma virus (HPV) causation in a distinct disease entity of oropharyngeal cancer (OPC), with an increasing incidence worldwide.This review aims to critically analyse whether a change in our management approaches to HPV-positive OPC is now required for this increasingly significant public health concern. Recent findingsHPV-positive OPC appears to have increased worldwide. HPV status has a strong prognostic effect, and, in combination with smoking status, primary, and nodal stage, is useful in the risk stratification of OPC. HPV-positive OPC responds better to chemoradiotherapy, surgery, and postoperative chemoradiotherapy than HPV-negative tumours, with improved survival outcomes. There remain concerns regarding the efficacy of HPV detection assays in clinical practice. HPV-negative head and neck cancer still accounts for the largest subset of patients that we treat and carries poor survival outcomes. SummaryIt is currently not advisable to change management for either HPV-positive or HPV-negative OPC as there is a lack of high-quality evidence to support this. High-quality randomized controlled trials are required to assess the efficacy of the different treatment modalities currently available for both HPV-positive and HPV-negative OPC.
Characterizing CD43 expression in haematogones using multicolor flow cytometric analysis

Haematogones are precursor B cells commonly detected in small numbers in the bone marrow. Morphologically, haematogones can mimic lymphoblasts and are best distinguished using multicolour flow cytometry with antibody combinations. Haematogones show characteristic and reproducible patterns of antigen expression representing the B‐cell maturation sequence. CD43 expression, widely seen in haematopoietic elements, has not been well characterized in haematogones. We demonstrate that CD43 is consistently expressed in haematogones in a reproducible pattern similar to that of CD10 when combined with CD20. We propose that in combination with other markers, CD43 can be useful in the identification of haematogones.
Improving Safety of Glucose Control in Intensive Care using Virtual Patients and Simulated Clinical Trials

Despite the potential clinical benefits of normalizing blood glucose in critically ill patients, the risk of hypoglycemia is a major barrier to widespread clinical adoption of accurate glycemic control. To compare five glucose control protocols, a validated insulin-glucose system model was employed to perform simulated clinical trials. STAR, SPRINT, UNC, Yale and Glucontrol protocols were assessed over a medical-surgical intensive care unit patient cohort. Results were interpreted separately for patients with low to high sensitivity to insulin, and low to high variability in metabolic state. STAR and SPRINT provided good glucose control with risk of severe hypoglycemia less than 0.05% across all patient groups. UNC also achieved good control for patients with low and medium levels of insulin sensitivity (SI), but risk of severe hypoglycemia was raised for patients with high SI. Glucontrol showed degradation of performance for patients with high metabolic variability.
Membrane Type 1 Matrix Metalloproteinase Induces Epithelial-to-Mesenchymal Transition in Prostate Cancer*

By mining DNA microarray data bases at GenBank™, we identified up-regulation of membrane type 1 matrix metalloproteinase (MT1-MMP) in human primary and metastatic prostate cancer specimens as compared with nonmalignant prostate tissues. To explore the role of up-regulated MT1-MMP in early stage cancer progression, we have employed a three-dimensional cell culture model. Minimally invasive human prostate cancer cells (LNCaP) were transfected with MT1-green fluorescent protein (GFP) chimeric cDNA as compared with GFP cDNA, and morphologic and phenotypic changes were characterized. GFP-expressing LNCaP cells formed multicellular spheroids with cuboidal-like epithelial morphology, whereas MT1-GFP-expressing cells displayed a fibroblast-like morphology and a scattered growth pattern in type I collagen gels. Cell morphologic changes were accompanied by decreased epithelial markers and enhanced mesenchymal markers, consistent with epithelial-to-mesenchymal transition. MT1-MMP-induced morphologic change and cell scattering were abrogated by target inhibition of either the catalytic domain or the hemopexin domain. We further demonstrated that MT1-MMP-induced phenotypic changes were dependent upon up-regulation of Wnt5a, which has been implicated in epithelial-to-mesenchymal transition. We conclude that MT1-MMP plays an important role in early cancer dissemination by converting epithelial cells to migratory mesenchymal-like cells.
Bioadhesive Microspheres for Ophthalmic Administration of Acyclovir

The bioavailability of acyclovir to the ophthalmic epithelium is low and when the drug is administered in ophthalmic ointment it must be applied every four hours. An emulsification technique has been used to prepare acyclovir‐loaded chitosan microspheres with the aim of promoting the prolonged release of drug and increasing its ocular bioavailability.
Usefulness of Microfat Grafting in Patients With Repaired Cleft Lip

AbstractIn many patients, the volume of the upper lip is deficient after cleft lip repair operation. However, there is no well-established procedure to correct this volume deficiency. In the present study, the authors attempted to increase the overall three-dimensional volume of the upper lip in repaired cleft lip patients with upper lip volume deficiency through autogenous microfat grafting. Thirty patients with upper lip volume deficiency after cleft lip repair underwent fat grafting in the upper lip from November 2007 to March 2015. Among these patients, postoperative outcome was evaluated in 15 patients using 2 methods for the evaluation. One method involved measuring the change in the shape of lips using pre- and postoperative photographs, and the other involved investigating the levels of satisfaction with the surgical results by distributing a scoring questionnaire to patients, doctors, and the general public. The ratio of upper lip protrusion relative to the lower lip increased by 46.71% on average after operation, and the sum of the vermilion heights increased by 31.68% on average. In the survey of satisfaction levels, patients, plastic surgeons, and the general public gave mean scores of 3.80, 3.91, and 4.03, respectively. When volume deficiency of the upper lip is present in repaired cleft lip patients, correction using autogenous microfat grafting is believed to be effective.
Analysis of in situ protease activity in chronic adult periodontitis patients: expression of activated MMP-2 and a 40 kDa serine protease.

BACKGROUND Periodontitis is characterized by extensive destruction of the gingival tissues and associated supporting structures of the teeth. Although the pathogenesis of the various forms of this disease is not completely understood, host-derived proteases are believed to have an important role. In this study, we analyzed human tissue samples from chronic adult periodontitis patients to assess the levels of specific proteases and determine the effect of pH and tetracyclines on their activity. METHODS Gingival tissue samples were obtained from patients with chronic adult periodontitis (probing depths ranged from 5 to 9 mm) and periodontally healthy controls. Tissue extracts were prepared and analyzed for protease activity by zymography and Western blotting. RESULTS Maximal protease activity from clinically normal and diseased tissues was observed at pH 8. Latent matrix metalloproteinase (MMP)-9 and MMP-2 were expressed in all samples examined, while active MMP-2 was detected only in tissues obtained from patients with clinical disease. The MMP activities were differentially inhibited by derivatives of tetracycline. At pH 6, a protease with a mass of approximately 40 kDa was observed in diseased samples. The enzymatic activity was inhibited by phenylmethylsulfonyl fluoride, suggesting it is a serine protease. CONCLUSIONS The results of the current study substantiate the proposed role of host-derived proteases in the pathogenesis of chronic adult periodontitis. Specifically, they indicate that activated MMP-2 and a 40 kDa serine protease are involved in tissue destruction associated with this form of periodontal disease and also suggest that tissue pH influences protease activity in situ.
The ASRS-6 Has Two Latent Factors

Objective: To test whether the Adult Self-Report Scale for ADHD, six-items version (ASRS-6), measures inattentiveness and hyperactivity independently. Method: The ASRS-6 was completed by 234 university students and 157 outpatients treated for drug dependence. In both samples, the ASRS-6 was subjected to two confirmatory factor analyses, one testing a one-factor model and the other testing a model with two correlated factors indicating inattentiveness and hyperactivity, respectively. Test–retest reliability of the subscales was tested on a subset of the student sample (n = 25). Results: In both samples, the one-factor solution did not fit the data, but the two-factor solution fit the data better. Subscales differed in their correlates in ways that mirror the correlates of inattentiveness and hyperactivity in the published literature on ADHD. In the student sample, the test–retest reliability was adequate for hyperactivity (r = .70) and inattentiveness (r = .77). Conclusion: The ASRS-6 measures two correlated constructs, rather than one unitary construct.
Cooling following large volcanic eruptions corrected for the effect of diffuse radiation on tree rings

The lack of a larger cooling in proxy records of climate change following large volcanic eruptions such as those of Tambora in 1815 and Krakatau in 1883 has long been a puzzle for climatologists. These records, however, may have been biased by enhanced tree growth for several years following each eruption induced by additional diffuse radiation caused by the stratospheric volcanic aerosol clouds from the eruptions. By comparing proxy reconstructions of climate with and without tree ring data, this effect is demonstrated for the five largest eruptions for the period 1750–1980. When proxy records of Northern Hemisphere climate change are corrected for this proposed diffuse effect, there is no impact on climate change for time scales longer than 20 years. However, it now appears that there was a hemispheric cooling of about 0.6°C for a decade following the unknown volcanic eruption of 1809 and Tambora in 1815, and a cooling of 0.3°C for several years following the Krakatau eruption of 1883.
EFFECTS OF THERMAL STRESS ON VIABILITY AND RIBONUCLEIC ACID OF AEROBACTER AEROGENES IN AQUEOUS SUSPENSION.

SUMMARY: The death-rate of washed Aerobacter aerogenes in aqueous suspension at 47° depended on the nature of the growth medium, the composition of the liquid used to wash and resuspend the bacteria, the bacterial growth phase, the bacterial concentration in heated suspensions, the pH value, the oxygen tension and the composition of the diluent in which bacteria were heated. The relative resistance of bacteria in different growth phases differed according to the growth medium and the washing fluid; stationary phase bacteria were not more resistant than exponential phase organisms under all conditions. Starvation increased the thermal resistance of exponential and stationary phase bacteria. High bacterial concentration favoured survival at 47° under most conditions; cell-free filtrate from a heated dense suspension (1010 bacteria/ml.) protected a sparser population of fresh bacteria (107-109/ml.) heated in it. Protective material in filtrate was heat-stable (100°/15 min.) and diffused through cellophan. The optimum pH value for survival at 47° was near pH 6·5. Aerobic conditions favoured survival in distilled water but not in salt solutions or phosphate saline (pH 6·5). The effects of various concentrations of NaCl and KCl on the survival of bacteria at 47° under aerobic conditions were different, K+ concentrations above 0·1 m being more lethal than equivalent concentrations of Na+; the lethal effect of heating in mixtures of these salts (total m > 0·1) increased with K+ concentration. Growth medium, Mg2+ (0·01–5 mm) and, to a lesser extent, Mn2+ (0·5 mm) or Co2+ (5 mm) decreased the death-rate, whereas ethylenediamine tetraacetic acid (mm), or various sugars, increased it. Mg2+ but not Mn2+ reversed the lethal effect of sugars. Generally, conditions which accelerated the death-rate of Aerobacter aerogenes at 47° also increased the rate of degradation of endogenous RNA. This was accompanied by an increase in the ultraviolet absorption of cold acid-extracts of bacteria and of the suspending fluid. Bacterial protein was degraded to a smaller extent. Depletion of RNA is probably not the primary cause of death at 47° but the effect on bacterial metabolism of a rapid increase in endogenous pool constituents resulting from RNA degradation may contribute to the lethal effect.
Unusually marked hypoxic sensitization to indoloquinone E09 and mitomycin C in a human colon‐tumour cell line that lacks DT‐diaphorase activity

Studies with purified DT‐diaphorase have shown that the enzyme is capable of catalyzing a two‐electron reduction of the novel indoloquinone E09 to a DNA‐damaging alkylating species. The aim of this study was to determine to what extent DT‐diaphorase may be involved in the metabolic activation of E09 and mitomycin C in both aerobic and hypoxic conditions. Two human colon‐carcinoma cell lines were used; HT29 has high levels of DT‐diaphorase whilst BE lacks this activity because of a point mutation in the NQOI gene. In aerobic conditions the 2 cell lines show similar sensitivities to a number of cytotoxic drugs including cisplatin, doxorubicin and etopo‐side. They are equally sensitive to the benzotriazine di‐N‐oxide SR 4233 but HT29 is more sensitive than BE to mitomycin C and E09. Sensitivity to SR 4233 is increased by about 100‐fold for both cell lines in hypoxic conditions. DT‐diaphorase‐deficient BE cells show markedly increased sensitivity to mitomycin C and particularly E09 in hypoxic conditions, whereas DT‐diaphorase‐rich HT29 cells show little hypoxic sensitization to these agents unless exposed in the presence of dicoumarol. These results suggest that DT‐diaphorase can reduce E09 and mitomycin C to potent cytotoxic species in aerobic conditions, and this activity predominates over the one‐electron‐reducing enzymes even in hypoxic conditions. In the absence of DT‐diaphorase activity, E09 and mitomycin C are reduced in hypoxic conditions, presumably by one‐electron‐reducing enzymes, to a similar or greater extent than is achieved with DT‐diaphorase.