Miracle-dz/UniFAR-FTUs huggingface dataset:
Letter by Jong et al regarding article, "dietary fish and omega-3 fatty acid consumption and heart rate variability in US adults".

To the Editor: We read with interest the recent report from Mozaffarian et al1 that consumption of ω-3 fatty acid containing fish is associated with increased heart rate variability (HRV) markers of vagal heart rate modulation. Importantly, in their analysis, higher HRV was accompanied by a lower risk of subsequent cardiac death. Their findings, which demonstrate the potential use of HRV indices as surrogate or secondary measures of treatment efficacy when evaluating preventive strategies for cardiovascular disease, raise 2 important questions for research on the HRV response to interventions such as diet. First, how would one characterize the magnitude of treatment effects such …
The Effect of Corporate Taxes on Firm Productivity in Korea

This paper explains how marginal corporate tax rate at the industry level affects individual firm productivity. I constructed the individual firm level data of over 1,000 firms in Korea from 1980 to 2010, and estimated an error correction model. Firm productivity was measured as total factor productivity, which denotes the residual of the estimated Cobb-Douglas production function. The results show that corporate taxes have a negative effect on firm productivity, and that the magnitude of productivity reduction from corporate taxes increases as the firm generates higher profitability. I also found that the total factor productivity of an individual firm increases faster in the sector which reveals faster growing productivity.
START or SMART? Timing of Antiretroviral Therapy Initiation and Cardiovascular Risk for People With Human Immunodeficiency Virus Infection

The Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection (START) study has reinforced the benefits of early initiation of antiretroviral therapy (ART). However, a notable secondary finding from that study was that immediate initiation of ART did not prevent cardiovascular disease (CVD) events (0.17 vs 0.20 events/1000 person-years, P = .65). This result appears to contradict a body of evidence, most notably from the Strategies for Management of Antiretroviral Therapy (SMART) study, which reported a 70% increased hazard of cardiovascular events for those deferring or interrupting treatment. Thus, an important unresolved question is whether the timing of ART impacts CVD risk. In this review, published data on relationships between timing of ART and CVD risk are reviewed. The data support a role for ART in mitigating CVD risk at lower CD4 counts, but data also suggests that, among those initiating therapy early, ART alone appears to suboptimally mitigate CVD risk. Additional interventions to address CVD risk among human immunodeficiency virus-infected populations are likely to be needed.
The Endocrine Regulation of Aging by Insulin-like Signals

Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor–1, growth hormone, and thyroid hormones are interdependent. In all species examined to date, endocrine manipulations can slow aging without concurrent costs in reproduction, but with inevitable increases in stress resistance. Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism.
Sustainable Wildlife Management and Legal Commercial Use of Bushmeat in Colombia: The Resource Remains at the Cross-Road

SUMMARY Most countries in the Amazon have no clear policy frameworks to provide a legal path for sustainable wildlife management (SWM), including the commercial use of bushmeat. In Colombia, despite efforts to provide more local autonomy in the management of natural resources and the openness towards the sustainable use of wildlife since the 1970s, there are still a number of legal and technical impediments that need to be addressed. In this research, we first compiled evidence of the current illegal trade of bushmeat to justify the need to clarify legal frameworks regulating the activity. Then, we explore the opportunities for legal commercial hunting by rural communities and highlight current bottlenecks. Finally, we report on lessons learnt from past initiatives of sustainable bushmeat use in the country. In our conclusion, we provide some practical recommendations to promote the sustainable use of wildlife, clarify the definition of commercial use for subsistence purposes and legalize sustainable local bushmeat trade by rural communities.
Clinical situations associated with difficult-to-control hypertension

There is no doubt that patients with high blood pressure (BP) are at higher cardiovascular and death risk than those subjects whose BP levels are below the admitted normal threshold. However, most of the epidemiological surveys show that BP is uncontrolled in more than fifty percent of hypertensive subjects. There are several reasons that can justify this lack of hypertension control, some of them depending on the patient, such as therapeutic adherence, or some related to the doctor, due to therapeutic inertia or reluctance to increment the number and doses of antihypertensive drugs. Sometimes the efficacy or adverse effects related to the antihypertensive drugs underlie the uncontrolled hypertension. And, finally, there are some clinical conditions that are associated with difficult-to-control hypertension. Among them, comorbidities such as diabetes, obesity, obstructive sleep apnoea syndrome or chronic kidney disease, but also drug-related hypertension or resistant hypertension. In this article we review the epidemiology and the conditions which are related to poorly controlled hypertension and that can explain why hypertension may become difficult-to-treat.
Neoteny and the Plesiomorphic Condition of the Plesiosaur Basicranium

Introduction Historically, the systematics of the Plesiosauria (Reptilia, Sauropterygia) were based largely on postcranial characters (Persson, 1963; Brown, 1981). Several factors account for this bias: plesiosaur skulls tend to be delicate and are often crushed even when preserved, postcranial elements are relatively common and cranial elements are not, lack of knowledge about the relationships of stem-group sauropterygians, and lack of knowledge of plesiosaur cranial anatomy itself. However, recent detailed examinations of plesiosaur cranial anatomy have identified many characters of use in plesiosaur systematics (Brown, 1993; Cruickshank, 1994; Storrs & Taylor, 1996; Storrs, 1997; Carpenter, 1997; Evans, 1999; O’Keefe, 2001, 2004), and the systematics of the group have changed markedly in response (Carpenter, 1997; O’Keefe, 2001, 2004). The work of Rieppel and others has clarified the anatomy and relationships of stem-group sauropterygians (Storrs, 1991; see Rieppel, 2000, for review). This work has laid the anatomic and phylogenetic foundations for a better understanding of plesiosaur cranial anatomy. The purpose of this paper is to describe the condition of the braincase in stratigraphically early and morphologically primitive plesiosaurs. Information on the braincase of plesiomorphic taxa is important because it establishes the polarity of characters occurring in more derived plesiosaurs. This paper begins with a short review of braincase anatomy in stem-group sauropterygians. Data on braincase morphology of the plesiomorphic plesiosaur genera Thalassiodracon and Eurycleidus are then presented and interpreted via comparison with other plesiosaurs, stemgroup sauropterygians, and stem diapsids (Araeoscelis). Early diapsids are relevant because plesiosaur skulls more closely resemble early diapsids than stem-group sauropterygians in several key areas. Plesiosaurs display a broad trend of delayed and reduced ossification compared with stem-group sauropterygians (Storrs, 1991). This trend is linked to the acquisition of a truly pelagic lifestyle in the Plesiosauria (Romer, 1956).
HLA-DR4 Molecules in Neuroendocrine Epithelial Cells Associate to a Heterogeneous Repertoire of Cytoplasmic and Surface Self Peptides1

Expression of MHC class II genes by epithelial cells is induced in inflammatory conditions such as autoimmunity and organ transplantation. Class II ligands generated by the epithelial cell processing mechanisms are unknown, although some unique epitopes have been described in epithelial cells that B cells could not generate. Epithelial cells are the targets of autoreactive T cell responses in autoimmune diseases and of transplant rejection processes, which may involve recognition of cell type-specific epitopes. In the present report, we have compared the DR4-associated repertoire and the intracellular distribution of class II, invariant chain (Ii), and DM molecules between a human DR4-, Ii-, and DM-transfected rat neuroendocrine epithelial cell line and a homozygous DR4 (DRB1*0401) lymphoblastoid B cell line, by mass spectrometry sequencing techniques, and immunoelectron microscopy. The epithelial cells chosen for transfection, RINm5F, are rat insular cells widely used for human studies of autoimmune diabetes. The results revealed a remarkably heterogeneous pool of self protein-derived peptides from the cell surface and various intracellular compartments, including the cytosol and secretory vesicles in epithelial cells, compared with a very restricted homogeneous repertoire in lymphoblastoid B cell lines, where few epitopes from surface molecules were predominant. The generation of distinct DR4-associated peptide repertoires in these two cell types could be due to the effect of several factors including differences in subcellular location of Ii and DM molecules, differential DO expression, and cell type-specific mechanisms of class II ligand generation. This is specially relevant to processes involving epithelial T cell interactions such as organ-specific autoimmunity and transplant rejection.
Treatment-experienced breast cancer: new pathways for improving survival. Introduction.

J. Aubrey WAddell, PhArm.d. , FAPhA, BCOP, is Associate Professor, University of Tennessee College of Pharmacy and Oncology Pharmacist, Blount Memorial Hospital, 2119 Scarlet Rose Court, Maryville, TN 37801 (JWaddell@bmnet.com). Based on the proceedings of a symposium held December 4, 2007, during the ASHP Midyear Clinical Meeting and Exhibition in Las Vegas, NV, and supported by an educational grant from Bristol-Myers Squibb Company. Dr. Waddell received an honorarium for his participation in the symposium and for the preparation of this article. Dr. Waddell reports having no affiliation with or financial interest in a commercial organization that poses a conflict with the authorship of this article.
Biweekly Administration of Docetaxel and Gemcitabine for Elderly Patients with Advanced Non-Small Cell Lung Cancer: A Phase II Study

Abstract With 69 years being the median age at diagnosis in the United States, management of elderly patients with advanced non-small cell lung cancer (NSCLC) has become a common problem faced by the oncology practitioner. We evaluated a biweekly administration of the combination regimen using docetaxel (Sanofi Aventis, Athens) and gemcitabine (Eli Lilly, Athens) in a phase II study (objective response rate, median survival, median response duration and safety). A total of 198 cycles were administered to 38 patients with advanced NSCLC with a median age of 72 years (range 65-85 years). Patients received docetaxel 80 mg/m2 and gemcitabine 1000 mg/m2 on days 1 and 14 of a 28-day cycle. Twenty patients achieved a partial response (PR) (20/34, 58.8%), 4 patients had stable disease (SD) (4/34, 11.7%) and 10 (10/34, 29.4%) had progressive disease (PD). The median time to disease progression was 3 months (range 1-11 months) with a mean survival of 7 months (range 1-29 months). Hematological and non-hematological toxic effects were generally mild to moderate and manageable: grade 3 neurotoxicity and grade 3 allergy occurred in 5 patients (13.1%) and 1 patient (2.6%), respectively. Peripheral neuropathy, mostly grades 1 and 2, was reported in 29 patients (76.3%), which was seen more frequently in patients >70 years of age (P=0.048). We conclude that the biweekly administration of a docetaxel/gemcitabine combination with G-CSF support constitutes a tolerable and convenient regimen for the treatment of elderly patients with advanced NSCLC, with efficacy similar to that reported in other regimens. Hence, this two-drug combination appears promising and warrants further evaluation.
Dickkopf‐1 regulates bone formation in young growing rodents and upon traumatic injury

The physiological role of Dickkopf‐1 (Dkk1) during postnatal bone growth in rodents and in adult rodents was examined utilizing an antibody to Dkk1 (Dkk1‐Ab) that blocked Dkk1 binding to both low density lipoprotein receptor‐related protein 6 (LRP6) and Kremen2, thereby preventing the Wnt inhibitory activity of Dkk1. Treatment of growing mice and rats with Dkk1‐Ab resulted in a significant increase in bone mineral density because of increased bone formation. In contrast, treatment of adult ovariectomized rats did not appreciably impact bone, an effect that was associated with decreased Dkk1 expression in the serum and bone of older rats. Finally, we showed that Dkk1 plays a prominent role in adult bone by mediating fracture healing in adult rodents. These data suggest that, whereas Dkk1 significantly regulates bone formation in younger animals, its role in older animals is limited to pathologies that lead to the induction of Dkk1 expression in bone and/or serum, such as traumatic injury. © 2011 American Society for Bone and Mineral Research
STEC-EPEC oligonucleotide microarray: a new tool for typing genetic variants of the LEE pathogenicity island of human and animal Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) strains.

BACKGROUND Shiga toxin-producing Escherichia coli (STEC) and enteropathogenic E. coli (EPEC) are important emerging pathogens that can cause a severe and sometimes fatal illness. Differentiation of eae, tir, espA, espD, and espB gene variants of the locus of enterocyte effacement (LEE) pathogenicity island represents an important tool for typing in routine diagnostics as well as in pathogenesis, epidemiologic, clonal, and immunologic studies. METHODS Type-specific oligonucleotide microarrays and a PCR scheme were designed and constructed for the detection and typing of genetic variants of the LEE genes. Oligonucleotide probes were tested for their specificity against the corresponding type strain by microarray hybridization using fluorescent DNA, either PCR-amplified (single, multiplex, long-range), chromosomal, or amplified chromosomal DNA. RESULTS The PCR scheme and the oligonucleotide microarray allowed us to distinguish 16 variants (alpha1, alpha2, beta1, beta2, gamma1, gamma2/theta, delta/kappa, epsilon, zeta, eta, iota, lambda, mu, nu, xi, omicron) of the eae gene, 4 variants (alpha1, beta1, gamma1, gamma2/theta) of the tir gene, 4 variants (alpha1, beta1, beta2, gamma1) of the espA gene, 3 variants (alpha1, beta1, gamma1) of the espB gene, and 3 variants (alpha1, beta1, gamma1) of the espD gene. We found a total of 12 different combinations of tir, espA, espB, and espD genes among the 25 typed strains. CONCLUSIONS The PCR scheme and the oligonucleotide microarray described are effective tools to rapidly screen multiple virulence genes and their variants in E. coli strains isolated from human and animal infections. The results demonstrate the great genetic diversity among LEE genes of human and animal STEC and EPEC strains.
A hypermorphic mouse Gli3 allele results in a polydactylous limb phenotype

Gli3 protein processing to generate the Gli3 repressor is mediated by proteasome and inhibited by Hedgehog signaling. The Gli3 repressor concentration is graded along the anterior–posterior axis of the developing vertebrate limb due to posteriorly restricted Sonic hedgehog expression. In this study, we created a small deletion at the Gli3 locus (Gli3Δ68), which causes a half reduction in the Gli3 repressor levels and a slightly increased activity of full‐length mutant protein in the limb. Mice homozygous for Gli3Δ68 develop one to two extra partial digits in the anterior of the limb, while mice carrying one copy of the Gli3Δ68 allele die soon after birth and display seven digits. These phenotypes are more severe than those found in mice lacking one wild‐type Gli3 allele. The expression of dHand, Hoxd12, and Hoxd13 is anteriorly expanded in the limb, even though no up‐regulation of Gli1 and Ptc RNA expression is detected. These findings suggest that a decrease in the Gli3 repressor level in combination with an increase in Gli3 full‐length activity results in more severe digit patterning abnormalities than those caused by a loss of one wild‐type Gli3 allele. Developmental Dynamics 236:769–776, 2007. © 2007 Wiley‐Liss, Inc.
Glutathione S transferase deficiency and passive smoking increase childhood asthma

Background: It has been suggested that the genetically determined deficiency of glutathione S transferase (GST) enzymes involved in the detoxification of environmental tobacco smoke (ETS) components may contribute to the development of asthma. Methods: A large population of German schoolchildren (n = 3054) was genotyped for deficiencies of the GST isoforms M1 and T1. The association between GSTM1 and GSTT1 genotypes and asthma as well as atopy was investigated with respect to current and in utero ETS exposure. Results: In children lacking the GSTM1 allele who were exposed to current ETS the risk for current asthma (OR 5.5, 95% CI 1.6 to 18.6) and asthma symptoms such as wheeze ever (OR 2.8, 95% CI 1.3 to 6.0), current wheezing (OR 4.7, 95% CI 1.8 to 12.6) and shortness of breath (OR 8.9, 95% CI 2.1 to 38.4) was higher than in GSTM1 positive individuals without ETS exposure. Hints of an interaction between ETS exposure and GSTM1 deficiency were identified. In utero smoke exposure in GSTT1 deficient children was associated with significant decrements in lung function compared with GSTT1 positive children not exposed to ETS. Conclusions: GSTM1 and GSTT1 deficiency may increase the adverse health effects of in utero and current smoke exposure.
T Helper‐Independent Activation of Human CD8+ Cells: the Role of CD28 Costimulation

The concept that activation of MHC class I‐restricted CD8+ cells entirely depends on help from MHC class II‐restricted CD4+ T cells has recently been supplemented with an alternative model in which CD8+ cells can directly be activated by MHC class I‐expressing professional antigen‐presenting cells (APC), which are able to deliver an accessory signal. The authors analysed the role of CD28‐mediated costimulation for T helper cell‐independent activation of purified human CD8+ T cells in two different in vitro models. Freshly isolated CD8+ cells could be activated (proliferation, IL‐2 production and cytotoxic activity) by anti‐CD3‐presenting FcγR+ mouse cells transfected with the human CD28 ligand, CD80, as the only accessory signal. On the other hand, activation of CD8+ cells by allogeneic MHC class I on EBV‐transformed B cells, which express two different CD28 ligands, CD80 and CD86, also proceeded very efficiently (proliferation, cytotoxic activity and CD25 expression), but was either not, or only partially, blocked by anti‐CD80 and anti‐CD86 MoAb or CTLA‐4Ig. This indicates that other costimulatory signals are also effective, and that CD28 triggering is not absolutely required for initial T‐cell activation. CsA and CD80/CD86‐blocking agents were synergistic in completely inhibiting activation of CD8+ cells in the MLR with allogeneic B‐cell lines. This combination also induced non‐responsiveness of CD8+ cells upon restimulation in the absence of blocking agents. Therefore, although professional APC can apparently provide multiple costimulatory signals for direct activation of CD8+ T cells, the signal derived from CD80/CD86 is unique in providing CsA‐resistance.
Determination of the lactate threshold and maximal blood lactate steady state intensity in aged rats

The reliability of the lactate threshold (LT) determined in aged rats and its validity to identify an exercise intensity corresponding to the maximal blood lactate steady state (MLSS) were analyzed. Eighteen male aged Wistar rats (∼365 days) were submitted to two incremental swimming tests until exhaustion, consisting of an initial load corresponding to 1% of body mass (BM) and increments of 1% BM at each 3‐min with blood lactate ([lac]) measurements. The LT was determined by visual inspection (LTV) as well by applying a polynomial function on the [lac]/workload ratio (LTP) by considering the vertices of the curve. For the MLSS, twelve animals were submitted, on different days, to 3–4 exercise sessions of 30‐min with workload corresponding to 4, 5 or 6% BM. The MLSS was considered the highest exercise intensity at which the [lac] variation was not higher than 0.07 mM.min−1 during the last 20‐min. No differences were observed for the test‐retest results (4.9 ± 0.7 and 5.0 ± 0.8 %BM for LTv; and 6.0 ± 0.6 and 5.8 ± 0.6 %BM for LTp) that did not differ from the MLSS (5.4 ± 0.5 %BM). The LT identified for aged rats in swimming, both by visual inspection and polynomial function, was reliable and did not differ from the MLSS. Copyright © 2009 John Wiley & Sons, Ltd.
Age-related changes in the expression of NMDA, serotonin, and GAD in the central auditory system of the rat

Abstract Conclusions: We suggest that age-induced changes of serotonin, N-methyl-d-aspartate receptor (NMDAR), and glutamate decarboxylase (GAD) expression in rats are dependent on the specific location in the central auditory system (CAS). Objectives: Despite the importance of understanding changes in neurotransmitters during presbycusis, only a few studies have assessed age-associated changes in neurotransmitter at each level of the CAS. We therefore evaluated effects of aging on neurotransmission in the CAS of rats. Methods: The concentrations of serotonin, NMDAR, and GAD were assayed immunohistochemically in the cochlear nucleus (CN), superior olivary nucleus (SON), inferior colliculus (IC), medial geniculate body (MGB), and auditory cortex (AC) of Sprague-Dawley rats, aged 2 weeks (n = 20) or 24 months (n = 20). Results: The total number of neuronal cell bodies of the CAS did not differ significantly at each level between young and aged rats (p > 0.05). Serotonin expression was increased with age in the IC and MGB, but decreased in the CN, SON, and AC (p < 0.05). NMDAR was significantly higher in the CN, MGB, and AC of aged compared with young rats, but was significantly decreased over time in the SOC and IC (p < 0.05). GAD67 was increased with age in the MGB and AC and decreased in the CN and SON (p < 0.05), but was not changed in the IC.