Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical applications of circulating oxidized low-density lipoprotein biomarkers in cardiovascular disease

Purpose of review The aim of this article is to review, analyze and interpret the growing body of evidence on circulating oxidized low-density lipoprotein and its relationship to diagnosis and prognosis of cardiovascular disease. Recent findings Previous studies focused on indirect measures of oxidative stress such as susceptibility of low-density lipoprotein to oxidation and measurement of autoantibodies to oxidized low-density lipoprotein. The generation of monoclonal antibodies recognizing distinct oxidation-specific epitopes has allowed the development of sensitive and specific assays to measure circulating oxidized low-density lipoprotein. Recent work in human populations has demonstrated that circulating oxidized low-density lipoprotein is associated with preclinical atherosclerosis, coronary and peripheral arterial atherosclerosis, acute coronary syndromes and vulnerable plaques. Several studies have also suggested that elevated levels of oxidized low-density lipoprotein are a prognostic indicator of cardiovascular outcomes. In addition, it has been shown that lipoprotein(a) is the primary carrier of oxidized phospholipids in the circulation of humans, suggesting additional mechanisms through which lipoprotein(a) may be pro-atherogenic. Summary Research on circulating oxidized low-density lipoprotein biomarkers is rapidly accelerating and providing novel insights into the pathophysiology of cardiovascular disease. Future studies will further assess the clinical utility of oxidized low-density lipoprotein biomarkers by determining their prognostic value in the diagnosis and prognosis of cardiovascular disease and will also evaluate the relative merit of specific assays by performing comparative studies.
Symptoms of PTSD following recovery of war dead: 13-15-month follow-up.

OBJECTIVE The authors explored whether individuals who participated in the recovery of war dead were more likely to experience later symptoms of posttraumatic stress disorder (PTSD) than were individuals who were not involved in the recovery of war dead. METHOD PTSD symptoms were assessed by questionnaire in men and women who had or had not handled human remains during the Persian Gulf War: 116 men and women who had and 118 who had not handled human remains participated in the study 3-5 months after returning from the war; 55 of the subjects who had and 56 of those who had not handled human remains participated in a follow-up assessment 13-15 months after their return. RESULTS Subjects who had been involved in the recovery of war dead had significantly higher symptom levels than comparison subjects at both time points. CONCLUSIONS After more than 1 year, individuals who had handled human remains during wartime were at higher risk for PTSD symptoms than those who had not.
Selectivity of Digitalis Glycosides for Isoforms of Human Na,K-ATPase*

There are four isoforms of the α subunit (α1–4) and three isoforms of the β subunit (β1–3) of Na,K-ATPase, with distinct tissue-specific distribution and physiological functions. α2 is thought to play a key role in cardiac and smooth muscle contraction and be an important target of cardiac glycosides. An α2-selective cardiac glycoside could provide important insights into physiological and pharmacological properties of α2. The isoform selectivity of a large number of cardiac glycosides has been assessed utilizing α1β1, α2β1, and α3β1 isoforms of human Na,K-ATPase expressed in Pichia pastoris and the purified detergent-soluble isoform proteins. Binding affinities of the digitalis glycosides, digoxin, β-methyl digoxin, and digitoxin show moderate but highly significant selectivity (up to 4-fold) for α2/α3 over α1 (KD α1 > α2 = α3). By contrast, ouabain shows moderate selectivity (≈2.5-fold) for α1 over α2 (KD α1 ≤ α3 < α2). Binding affinities for the three isoforms of digoxigenin, digitoxigenin, and all other aglycones tested are indistinguishable (KD α1 = α3 = α2), showing that the sugar determines isoform selectivity. Selectivity patterns for inhibition of Na,K-ATPase activity of the purified isoform proteins are consistent with binding selectivities, modified somewhat by different affinities of K+ ions for antagonizing cardiac glycoside binding on the three isoforms. The mechanistic insight on the role of the sugars is strongly supported by a recent structure of Na,K-ATPase with bound ouabain, which implies that aglycones of cardiac glycosides cannot discriminate between isoforms. In conclusion, several digitalis glycosides, but not ouabain, are moderately α2-selective. This supports a major role of α2 in cardiac contraction and cardiotonic effects of digitalis glycosides.
A peptide tetramer Tk‐tPN induces tolerance of cardiac allografting by conversion of type 1 to type 2 immune responses via the Toll‐like receptor 2 signal‐promoted activation of the MCP1 gene

The plant protein trichosanthin (Tk) and its derived peptide tetramer Tk‐tPN have been shown to stimulate the type 2 immune responses for treating autoimmune disease. This work explores the possibility of using Tk‐tPN as a non‐toxic immunosuppressant to induce transplantation tolerance using the mechanisms by which T‐cell‐mediated immune responses are transferred from type 1 to type 2 through innate immunity‐related pathways. Immunocytes and cytokine secretions involved in the mouse cardiac allografting model with Tk‐tPN treatment were characterized. Identification of critical genes and analysis of their functions through Toll‐like receptor (TLR) ‐initiated signalling and the possible epigenetic changes were performed. Mean survival times of the cardiac allografts were delayed from 7·7 ± 0·3 days (control) to 22·7 ± 3·9 days (P < 0·01) or 79·1 ± 19·2 days (P < 0·0001) when Tk‐tPN was introduced into the recipients alone or together with rapamycin, respectively. The grafting tolerance was donor‐specific. The secretion pattern of the type 1 cytokine/transcription factor (IL‐2+ IFN‐γ+ T‐bet+), which is responsible for the acute graft rejection, was shifted to the type 2 factor (IL‐4+ IL‐10+ Gata3+), together with a selective expansion of the IL‐4/IL‐10‐producing CD8+ CD28− regulatory T‐cell subset. A TLR2‐initiated high expression of chemokine gene MCP1 was detectable simultaneously. Epigenetically Tk/Tk‐tPN could also acetylate the histone H3K9 of MCP1 promoter to skew the immunity towards T helper type 2 responses. Tk/Tk‐tPN is therefore capable of down‐regulating the type 1 response‐dominant rejection of cardiac allografts by evoking type 2 immunity through the activation of a TLR2‐initiated signalling pathway and MCP1 gene to expand the IL‐4/IL‐10‐secreting CD8+ CD28− regulatory T cells. Tk‐tPN could be a promising novel immunosuppressant to induce tolerance in allotransplantation.
Modulation of Mitogenic Activity of Fibroblast Growth Factors by Inorganic Polyphosphate*

The proliferation of normal human fibroblast cells was enhanced by the addition of inorganic polyphosphate (poly(P)) into culture media. The mitogenic activities of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) were also enhanced by poly(P). A physical interaction between poly(P) and FGF-2 was observed, and FGF-2 was both physically and functionally stabilized by poly(P). Furthermore, poly(P) facilitated the FGF-2 binding to its cell surface receptors. Because poly(P) is widely distributed in mammalian tissues, it may be a spontaneous modulator of FGFs.
Expression of the crystal protein gene under the control of the alpha-amylase promoter in Bacillus thuringiensis strains

The expression of an insecticidal crystal protein gene of Bacillus thuringiensis under the control of the alpha-amylase gene promoter was investigated. The cryIC gene, which encodes a protein known to have a unique activity against Spodoptera (armyworm) species, was used in this investigation. The cryIC gene was placed, along with the alpha-amylase promoter from B. subtilis, in a B. thuringiensis-derived cloning vector, generating a pair of recombinant plasmids, pSB744 and pSB745. The cloning vector that contains the minimal replicon of B. thuringiensis subsp. kurstaki HD73 is stably maintained in a variety of B. thuringiensis strains, as previously reported by Gamel and Piot (Gene 120:17-26, 1992). The present study confirmed that the recombinant plasmids are also stably maintained in B. thuringiensis subsp. kurstaki Cry-B and HD73 growing in media without selection pressure for at least 48 h. The cryIC gene on the recombinant plasmids were notably expressed at high levels in both recombinant strains. Expression of the introduced cryIC gene on the recombinant plasmid in B. thuringiensis subsp. kurstaki HD73 did not impair expression of the resident cryIA(c) gene. The CryIA(c) protein is known to have a high level of activity against loopers such as Trichoplusia ni (the cabbage looper). As a result of coexpression of the introduced cryIC gene and the resident cryIA(c) gene, recombinant strain HD73 acquired an additional insecticidal activity against Spodoptera exigua (the beet armyworm) whereas the original activity level against T. ni was maintained.
Health Status of Haenyeo Who Visited the Emergency Department

Professional female free divers (Haenyeo) in Korea have been exposed to breathing in the water without any respiratory equipment and are increasingly aging. However, data on their general health status are scarce. A total of 733 electronic medical records of 480 professional female free divers who visited the emergency department from July 2012 to June 2013 were analyzed. Their mean age was 74.3 years, and 87.4% were 65 years or older. Most women had one or more comorbid conditions and were taking medication. The most common discharge diagnosis based on the International Classification of Disease-10 was symptomsand abnormal clinical and laboratory findings. Furthermore, 12.3% had a discharge diagnosis related to injury, and almost half of the injuries were caused by slip down. Older professional female free divers were more likely to have comorbid conditions and take medication, and have discharge diagnoses related to slipdown injury, and digestive, respiratory, and circulatory conditions more frequently. Therefore, specific symptoms related to diving and various age-related aspects such as injury prevention and chronic disease management should be considered in developing a health program for professional female free divers.
Heart block and empirical therapy after transcatheter closure of perimembranous ventricular septal defect

Two patients with perimembranous ventricular septal defects (VSDs) and inlet extension have undergone uncomplicated transcatheter device closure using the Amplatzer membranous VSD device. Both patients developed complete heart block 2–4 days from the closure. Both patients responded well to high‐dose intravenous therapy with steroids and high‐dose oral anti‐inflammatory aspirin. Both patients remain in normal sinus rhythm 8 weeks and 10 months, respectively, from the episode. © 2005 Wiley‐Liss, Inc.
Higher than Physician’s Desk Reference (US) doses on atypical antipsychotics

The Physician’s Desk Reference (PDR) was established to provide for the practicing of a complete listing of all medications with the FDA-approved labelling, including dosage recommendations. Perhaps in order to maximise individual usage of medications, pharmaceutical companies have frequently targeted lowest possible doses for FDA approval. However, many patients with a variety of illnesses due to resistance and/or multiple illnesses, may need higher than these dose ranges to maximise therapeutic response. In terms of regularly prescribed atypical antipsychotics released over the past 10 years, only risperidone initially obtained approval for a dose for psychosis (16 mg) higher than that suggested currently (maximum of 8 mg). The dose that was approved for mania was lower: a maximum of 6 mg. The others: respectfully, olanzapine (schizophrenia:15 mg, mania:20 mg), quetiapine (schizophrenia: 750 mg; mania: 800 mg), ziprasidone (schizophrenia and mania: 160 mg) and aripiprazole (schizophrenia and mania: 30 mg) obtained approvals for psychosis that may limit adverse events but, at the same time, limit benefits. Other data from various sources (double-blind trials, open-label trials, reviews and case reports) have found safety and/or efficacy for the following maximum doses: olanzapine (40 mg), quetiapine (1600 mg), ziprasidone (320 mg) and aripiprazole (75 mg). Reports above those doses are included, but either are insufficient in numbers or bring up questions on safety. In many situations, feared increase in adverse events were not magnified by use of higher doses.
DNA Ligase IV and XRCC4 Form a Stable Mixed Tetramer That Functions Synergistically with Other Repair Factors in a Cell-free End-joining System*

Repair of DNA double-strand breaks in mammalian cells occurs via a direct nonhomologous end-joining pathway. Although this pathway can be studied in vivo and in crude cell-free systems, a deeper understanding of the mechanism requires reconstitution with purified enzymes. We have expressed and purified a complex of two proteins that are critical for double-strand break repair, DNA ligase IV (DNL IV) and XRCC4. The complex is homogeneous, with a molecular mass of about 300,000 Da, suggestive of a mixed tetramer containing two copies of each polypeptide. The presence of multiple copies of DNL IV was confirmed in an experiment where different epitope-tagged forms of DNL IV were recovered simultaneously in the same complex. Cross-linking suggests that an XRCC4·XRCC4 dimer interface forms the core of the tetramer, and that the DNL IV polypeptides are in contact with XRCC4 but not with one another. Purified DNL IV·XRCC4 complex functioned synergistically with Ku protein, the DNA-dependent protein kinase catalytic subunit, and other repair factors in a cell-free end-joining assay. We suggest that a dyad-symmetric DNL IV·XRCC4 tetramer bridges the two ends of the broken DNA and catalyzes the coordinate ligation of the two DNA strands.
Prevalence and Patterns of Condom Use Among Patients Attending a Sexually Transmitted Disease Clinic

The purpose of this study is to evaluate prevalence and patterns of condom use among patients attending a sexually transmitted disease (STD) clinic, who are at increased risk of developing STDs. Interviews of 800 patients attending a Baltimore STD clinic were conducted. The prevalence of condom use was dependent on the measure of use employed. For example, 9 out of 10 patients reported ever having used condoms, slightly less than one-third of the patients reported having used condoms in the past 30 days, and only 17% of the patients reported using a condom at last sex. Use also varied somewhat by type of sexual partner, and within any given relationship, from first to last sexual encounter. The most significant factor corresponding to condom use in the 30 days prior to the interview was number of sexual partners (lifetime and in the last month). Multivariate analyses revealed number of lifetime partners to be the most significant predictor of condom use for men, whereas age was the most significant variable for women. These findings suggest that interventions should focus not only on the individual, but the couple.
The Economic Impact of Forced Migration

The current refugee crisis is a catastrophe affecting millions of families, endangering the stability of nations that are hosts to large numbers of migrants, and of the region around them. Forced migration flows which are mismanaged, as at present, create large negative political and economic externalities for the world as a whole. Concerns of advanced countries that accepting forced migrants will cause job losses or falling wages, and place an undue burden on the public purse, are largely unjustified. Although there is no perfect scheme for allocating the burden, any solution must envisage increased numbers of refugees settling in the North and increased aid for the countries in the South with the largest numbers of refugees.
The validity of pap smear parameters as predictors of endometrial pathology in menopausal women

Cytopathologists recognize that certain Pap smear findings are suspicious for endometrial pathology in menopausal women. To study their prognostic importance in the directed cervical smear, six parameters were used to evaluate smears for evidence of an endometrial lesion: the presence of (1) histiocytes, (2) multinucleated histiocytes, (3) nonspecific inflammation, (4) bleeding, (5) elevated squamous cell maturation index, and (6) the degree of cytologic atypicality of endometrial glandular cells, expressed as a ‘score’ from 0 to 6. Clinical pathologic correlation of 102 women with these parameters was undertaken. A multivariable statistical analysis determined which of these six parameters was most predictive of an endometrial lesion. Cytologically ‘scored’ endometrial glandular cells was the only parameter predictive of endometrial pathology. Its emergence as the sole prognostic cervical Pap smear parameter for endometrial pathology has not been previously reported. This predictive value was consistent even with control for bleeding history and age. Appropriate interpretation of abnormal Pap smear findings contributes substantial diagnostic information in the evaluation of the endometrium.
Clinical use of fresh-frozen plasma and cryoprecipitate in neonatal intensive care unit

Evidence-based indications for the use of plasma products in neonatal medicine are limited to few conditions. In the setting of inherited disorders of hemostasis, fresh frozen plasma (FFP) and cryoprecipitate should be used as replacement therapy only if the specific factor concentrate is not available. FFP is indicated to treat disseminated intravascular coagulation (DIC), liver failure, vitamin K-dependent bleeding and to reconstitute whole blood for exchange transfusion. Despite the lack of evidence, the use of cryoprecipitate to treat neonates with acquired hypofibrinogenemia during DIC or liver failure is now considered standard therapy.
Lack of ABC transporter autoinduction in mice following long-term exposure to imatinib

Purpose: Chronic imatinib exposure has been shown to result in upregulation of the ABCB1 (P-glycoprotein) and ABCG2 (BCRP) transporters in vitro, for which imatinib is a substrate. This finding, along a trend towards increasing imatinib clearance over time in patients, has resulted in the suggestion that pharmacokinetic resistance may be contributing to eventual treatment failure. Here, we sought to determine the effects of long-term imatinib exposure on apparent oral clearance and transporter expression in vivo.Methods: Male BALB/c mice were treated daily-times 5 with oral imatinib at a dose of 50 mg/kg for 4 consecutive weeks. Imatinib concentrations were measured in plasma and liver tissue prior to treatment and following each week of dosing. Western blotting of liver and intestinal tissue lysates was performed to assess expression of Abcb1 and Abcg2.Results: Plasma and liver concentrations of imatinib did not change significantly (P > 0.1) over the course of treatment, suggesting that steady-state had been reached. There was no increase in Abcb1 or Abcg2 expression in liver samples, whereas expression of these transporters in intestinal samples was highly variable, and no increase was apparent.Conclusions: Imatinib does not appear to cause upregulation of ABC transporters in the hepatic and intestinal compartments in mice. These data do not support the possibility that autoinduction contributes to the development of resistance to imatinib.
In vivo cytokine profiles in allergic and irritant contact dermatitis

Local cytokine profiles in skin biopsies from allergic and irritant patch test reactions were determined by in vivo immunohistochemistry to differentiate between these 2 clinically identical afflictions especially at the time of final reading in diagnostic patch testing. Biopsies were taken from established allergic persons after specific allergic patch test. ‐, to epoxy resin (1%) and formaldehyde (1%) and from non‐allergic individuals with irritant patch tests to sodium lauryl sulfate (10%) and formaldehyde (8%). At 72 h after application of the agents, significantly enhanced frequencies of dermal infiltrating cells, producing IL‐1α, TNF‐α. IL‐2. and IFN‐γ per 100 infiltrating cells in the dermis. were observed in allergic as well us irritant patch test reactions, as compared to normal skin. Significantly higher frequencies of IL‐ Iα‐producing cells were observed in biopsies from epoxy resin (1%) allergen‐affected and sodium lauryl sulfate (10%) irritant‐affected skin as compared to formaldehyde (1%) allergen‐affected skin. In addition, significantly higher frequencies of TNF ‐α reproducing cells were observed in epoxy resin allergen‐affected skin us compared to Formaldehyde (1%) allergen‐affected and formaldehyde (8%) irritant affected skin. The allergic and irritant patch test reactions showed similar levels of expression of the Thl cytokines IL‐2 and IFN‐γ in the dermis. confirmed by probe based detection of IL‐2 mRNA and IFN‐γ‐ mRNA, In conclusion, the described similarity shows that allergens and irritants can induce the same profile of IL‐la. TNF‐α. IL‐2. and IFN‐γ production, resulting in the near impossibility of discriminating between allergic and irritant contact dermal is at the lime of patch test reading.
Macrophage Secretory Phospholipase A2 Group X Enhances Anti-inflammatory Responses, Promotes Lipid Accumulation, and Contributes to Aberrant Lung Pathology*

Secreted phospholipase A2 group X (sPLA2-X) is one of the most potent enzymes of the phospholipase A2 lipolytic enzyme superfamily. Its high catalytic activity toward phosphatidylcholine (PC), the major phospholipid of cell membranes and low-density lipoproteins (LDL), has implicated sPLA2-X in chronic inflammatory conditions such as atherogenesis. We studied the role of sPLA2-X enzyme activity in vitro and in vivo, by generating sPLA2-X-overexpressing macrophages and transgenic macrophage-specific sPLA2-X mice. Our results show that sPLA2-X expression inhibits macrophage activation and inflammatory responses upon stimulation, characterized by reduced cell adhesion and nitric oxide production, a decrease in tumor necrosis factor (TNF), and an increase in interleukin (IL)-10. These effects were mediated by an increase in IL-6, and enhanced production of prostaglandin E2 (PGE2) and 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2). Moreover, we found that overexpression of active sPLA2-X in macrophages strongly increases foam cell formation upon incubation with native LDL but also oxidized LDL (oxLDL), which is mediated by enhanced expression of scavenger receptor CD36. Transgenic sPLA2-X mice died neonatally because of severe lung pathology characterized by interstitial pneumonia with massive granulocyte and surfactant-laden macrophage infiltration. We conclude that overexpression of the active sPLA2-X enzyme results in enhanced foam cell formation but reduced activation and inflammatory responses in macrophages in vitro. Interestingly, enhanced sPLA2-X activity in macrophages in vivo leads to fatal pulmonary defects, suggesting a crucial role for sPLA2-X in inflammatory lung disease.