Cross sectional study of depression, anxiety and quality of life in glaucoma patients at a tertiary centre in North Kerala.
To determine the magnitude and direction of association of anxiety and depression and the quality of life (QoL) in persons with glaucoma. This prospective cross-sectional study in conducted in a tertiary eye center in north Kerala included glaucoma patients and normal subjects aged 40-80 years. The Patient Health Questionnaire-9 (PHQ-9), the Generalized Anxiety Disorder-7 (GAD-7), Glaucoma Quality of Life (GQOL), and glaucoma evaluation were performed for all participants. One-way analysis of variance was used for statistical analysis. The study included 148 subjects with glaucoma and 150 subjects without glaucoma. The prevalence of depression (35.81%) and anxiety (25.0%) was significantly higher in glaucoma patients. In a multivariate regression model, PHQ-9 (adjusted OR: 2.39, 95% CI: 1.31-4.38, P < 0.001), GAD-7 (adjusted OR: 2.06, 95% CI: 1.01-4.19, P = 0.01) and GQOL (coefficient: 6.92, 95% CI: 4.52-9.31, P = < 0.001) was significantly associated with glaucoma. The GAD-7 score was significantly higher (P = 0.02) in PACG compared to POAG in moderate and severe anxiety. ADL scores (one-way ANOVA, P = 0.001) and GQOL scores (one-way ANOVA, P < 0.001) were significantly associated with vision impairment and blindness. Depression and anxiety are common in glaucoma patients, indicating the need for screening protocols using PHQ and GAD scales to identify persons at risk. The lack of ophthalmic risk factors associated with depression and anxiety emphasizes the importance of psychological evaluation and combined management with a psychiatrist in glaucoma management.


Human vascular smooth muscle cell-monocyte interactions and metalloproteinase secretion in culture.
Degradation of the atherosclerotic plaque extracellular matrix could destabilize the lesion, rendering it more prone to rupture. Both macrophages and vascular smooth muscle cells (SMCs) are potential sources of matrix metalloproteinases (MMPs), secreted enzymes that can digest vascular matrix. We explored interactions between human vascular SMCs and human monocytes that result in the secretion of interstitial collagenase (MMP-1) and stromelysin (MMP-3). Monocytes alone or those treated with SMC-conditioned media did not secrete these metalloproteinases as detectable by Western blot analysis. SMCs increased secretion of both MMP-1 and MMP-3 greater than 20-fold when cocultured with monocytes or when treated with monocyte-conditioned media. Addition of macrophage colony stimulating factor (< or = 1000 U/mL) to cocultures of monocytes and SMCs did not affect metalloproteinase secretion. Recombinant interleukin (IL)-1 receptor antagonist inhibited MMP-1 and MMP-3 induction in SMC cultures treated with monocyte-conditioned media (94% and 96% reduction, respectively), while a neutralizing antibody to tumor necrosis factor-alpha had no significant effect on metalloproteinase secretion. In contrast to the induction by monocyte-conditioned media of MMP-1 and MMP-3 secretion by SMCs, monocyte-conditioned media did not increase secretion of 72-kD gelatinase (MMP-2). Thus, monocytes induce MMP-1 and MMP-3 secretion by vascular SMCs through an IL-1-dependent mechanism. This response of SMCs to a defined macrophage product may contribute to plaque destabilization by mononuclear phagocytes in the lesion.


Endogenous HLA-DQ8αβ programs superantigens (SEG/SEI) to silence toxicity and unleash a tumoricidal network with long-term melanoma survival.
As the most powerful T cell agonists known, superantigens (SAgs) have enormous potential for cancer immunotherapy. Their development has languished due to high incidence (60%-80%) of seroreactive neutralizing antibodies in humans and tumor necrosis factor-α (TNFα)-mediated cardiopulmonary toxicity. Such toxicity has narrowed their therapeutic index while neutralizing antibodies have nullified their therapeutic effects. Female HLA-DQ8 (DQA*0301/DQB*0302) tg mice expressing the human major histocompatibility complex II (MHCII) HLA-DQ8 allele on a high proportion of PBL, spleen and lymph node cells were used. In the established tumor model, staphylococcal enterotoxin G and staphylococcal enterotoxin I (SEG/ SEI) (50 µg each) were injected on days 6 and 9 following tumor inoculation. Lymphoid, myeloid cells and tumor cell digests from tumor tissue were assayed using flow cytometry or quantitated using a cytometric bead array. Tumor density, necrotic and viable areas were quantitated using the ImageJ software. In a discovery-driven effort to address these problems we introduce a heretofore unrecognized binary complex comprizing SEG/SEI SAgs linked to the endogenous human MHCII HLA-DQ8 allele in humanized mice. By contrast to staphylococcal enterotoxin A (SEA) and staphylococcal enterotoxin B (SEB) deployed previously in clinical trials, SEG and SEI does not exhibit neutralizing antibodies in humans or TNFα-mediated toxicity in humanized HLA-DQ8 mice. In the latter model wherein SAg behavior is known to be 'human-like', SEG/SEI induced a powerful tumoricidal response and long-term survival against established melanoma in 82% of mice. Other SAgs deployed in the same model displayed toxic shock. Initially, HLA-DQ8 mediated melanoma antigen priming, after which SEG/SEI unleashed a broad CD4+ and CD8+ antitumor network marked by expansion of melanoma reactive T cells and interferon-γ (IFNy) in the tumor microenvironment (TME). SEG/SEI further initiated chemotactic recruitment of tumor reactive T cells to the TME converting the tumor from 'cold' to a 'hot'. Long-term survivors displayed remarkable resistance to parental tumor rechallenge along with the appearance of tumor specific memory and tumor reactive T memory cells. Collectively, these findings show for the first time that the SEG/SEI-(HLA-DQ8) empowers priming, expansion and recruitment of a population of tumor reactive T cells culminating in tumor specific memory and long-term survival devoid of toxicity. These properties distinguish SEG/SEI from other SAgs used previously in human tumor immunotherapy. Consolidation of these principles within the SEG/SEI-(HLA-DQ8) complex constitutes a conceptually new therapeutic weapon with compelling translational potential.


Optically Transparent Flexible Broadband Metamaterial Absorber Based on Topology Optimization Design.
A conformal metamaterial absorber with simultaneous optical transparency and broadband absorption is proposed in this paper. The absorptance above 90% over a wide frequency range of 5.3-15 GHz can be achieved through topology optimization combined with a genetic algorithm (GA). The broadband absorption can be kept at incident angles within 45° and 70° for TE mode and TM mode, respectively. In the meantime, by employing transparent substrates, including polyvinyl chloride (PVC) and polyethylene terephthalate (PET), good optical transmittance and flexibility can be obtained simultaneously. The experimental results agree well with the numerical simulations, which further validates the reliability of our design and theoretical analysis. With its visible-wavelength transparency, flexibility, broadband absorption, low profile, excellent angle stability and polarization insensitivity, the proposed absorber is highly favored for practical applications in microwave engineering, such as electromagnetic interference and stealth technology. Moreover, the proposed design method of topology optimization can be extended to design the absorber quickly and efficiently, according to specific engineering requirements.


Respiratory syncytial virus infections in pediatric liver transplant recipients.
Respiratory syncytial virus (RSV) is the most important cause of lower respiratory tract infection in infants and young children. The charts of 17 children found to have RSV among 493 children who underwent liver transplantation between February 1985 and February 1991 were reviewed. The median age at diagnosis was 20 months. Median time of diagnosis was 24 days after transplantation. Thirteen patients developed nosocomial infections while convalescing from their transplant. Common symptoms included tachypnea, cough, fever, and congestion. Acute radiographic changes were seen in 12 patients. Two deaths were associated with progressive pulmonary disease and occurred in children with infection early in the postoperative period who were intubated before the onset of symptoms. RSV in children after liver transplantation has a clinical spectrum similar to that in normal children. Early onset of infection (less than 20 days) after transplantation and preexisting lung disease may predict more severe disease.


Coexistence of Autoimmune Hyper- and Hypothyroidism in a Kindred with Reduced Sensitivity to Thyroid Hormone.
Resistance to thyroid hormone beta (RTHβ) is a rare disease with an autosomal dominant transmission. Diagnosis may be challenging especially in patients with hyper- or hypothyroidism. A 31-year-old male patient with suppressed thyroid-stimulating hormone (TSH), elevated free thyroxine and free triiodothyronine, along with high thyroid receptor antibodies was diagnosed with Graves' disease. Benzylthiouracil was started. One month later, reduced sensitivity to thyroid hormones was suspected because of persistently high thyroid hormone levels contrasting with high TSH level. Molecular analysis highlighted a 10c.1357C>T p.P453S mutation in the thyroid hormone receptor beta gene (THRB). RTHβ was diagnosed. Several relatives also had RTHβ (the mother, the young son, and 2 out of 3 siblings). Autoimmune hypothyroidism was present in the mother, whereas 2 out of 3 siblings had asymptomatic autoimmunity. Both Graves' disease and autoimmune hypothyroidism were described in patients with RTHβ. We show here for the first time that autoimmune hypo- and hyperthyroidism may coexist in kindred with RTHβ. Seven previously published cases of Graves' disease and RTHβ were retrieved and analyzed. Treatments and thyroid hormone level targets are discussed as well as the possible link between RTHβ and autoimmune thyroid diseases.


[Disseminated melanoma treatment].
Disseminated melanoma is an incurable disease whose prognosis has remained unchanged over the past 20 years. To date, no consensus treatment has emerged. No treatment strategy has proved superior to dacarbazine (Deticene) monochemotherapy that remains considered as the reference treatment for this disease. Both multidrug chemotherapy and biochemotherapy have provided disappointing results, with poorer quality of life and no survival benefit for the patients. Other treatment approaches, particularly immunotherapy, remain to be investigated in clinical trials.


Thiol switches in membrane proteins - Extracellular redox regulation in cell biology.
Redox-mediated signal transduction depends on the enzymatic production of second messengers such as hydrogen peroxide, nitric oxide and hydrogen sulfite, as well as specific, reversible redox modifications of cysteine-residues in proteins. So-called thiol switches induce for instance conformational changes in specific proteins that regulate cellular pathways e.g., cell metabolism, proliferation, migration, gene expression and inflammation. Reduction, oxidation and disulfide isomerization are controlled by oxidoreductases of the thioredoxin family, including thioredoxins, glutaredoxins, peroxiredoxins and protein dsisulfide isomerases. These proteins are located in different cellular compartments, interact with substrates and catalyze specific reactions. Interestingly, some of these proteins are released by cells. Their extracellular functions and generally extracellular redox control have been widely underestimated. Here, we give an insight into extracellular redox signaling, extracellular thiol switches and their regulation by secreted oxidoreductases and thiol-isomerases, a topic whose importance has been scarcely studied so far, likely due to methodological limitations. We focus on the secreted redox proteins and characterized thiol switches in the ectodomains of membrane proteins, such as integrins and the metalloprotease ADAM17, which are among the best-characterized proteins and discuss their underlying mechanisms and biological implications.


Persistence of BCR-ABL genomic rearrangement in chronic myeloid leukemia patients in complete and sustained cytogenetic remission after interferon-alpha therapy or allogeneic bone marrow transplantation.
In recent years, the prognosis of chronic myeloid leukemia (CML) has been greatly improved either with interferon-alpha (IFN-alpha) therapy or allogeneic bone marrow transplantation (BMT). In the present study, minimal residual disease was evaluated in 21 patients in complete cytogenetic response (CCR) after such treatments. Samples from bone marrow aspirates or peripheral blood or both were analyzed by conventional cytogenetics, Southern blot, interphase fluorescent in situ hybridization (FISH), and quantitative reverse transcription-polymerase chain reaction (Q-RT-PCR). In all patients, FISH detected 1% to 12% nuclei with a BCR-ABL fusion gene, whereas Q-RT-PCR experiments were negative or weakly positive. Based on these results, we hypothesize that the BCR-ABL genomic rearrangement persists unexpressed in nonproliferating cells whatever the treatment (IFN-alpha or BMT). These data point to the need for follow-up of CML patients in CCR over an extensive period at the DNA level (FISH) to evaluate the residual disease and at the RNA level (Q-RT-PCR) to estimate the risk of relapse. (Blood. 2000;95:404-408)


Postinfarction cardiac rupture after coronary revascularization.
Rupture of the myocardium is a catastrophic complication of acute myocardial infarction. Coronary revascularization has been increasingly utilized for the treatment of postinfarction angina. Further, myocardial infarction is a well known complication of coronary revascularization. Nonetheless, cardiac rupture after coronary revascularization has been rarely described. Described herein are three such cases with a review of the literature.


The Role of Seminal Oxidative Stress Scavenging System in the Pathogenesis of Sperm DNA Damage in Men Exposed and Not Exposed to Genital Heat Stress.
Responding to the need for the verification of some experimental animal studies showing the involvement of oxidative stress in germ cell damage in the heat-induced testis, we investigated the possibility of a direct relationship between seminal oxidative stress markers (total antioxidant capacity, catalase activity, superoxide dismutase activity, and malondialdehyde concentration) and ejaculated sperm chromatin/DNA integrity (DNA fragmentation and chromatin condensation abnormalities) in distinct groups of men exposed and not exposed to prolonged scrotal hyperthermia. A statistical increase in the proportion of sperm with DNA fragmentation was observed in all the studied subgroups compared to the fertile men. In turn, the groups subjected to heat stress as professional drivers or infertile men with varicocele presented greater disturbances in the oxidative stress scavenging system than men not exposed to genital heat stress. Based on the comparative analysis of the studied parameters, we can conclude that alterations in the seminal oxidative stress scavenging system are directly engaged in the pathogenesis of ejaculated sperm DNA damage regardless of the intensity of the impact of thermal insult. To the best of our knowledge, this study, for the first time, revealed the co-existence of oxidative stress and sperm DNA damage in the semen of professional drivers.


Application of Stereolithography Based 3D Printing Technology in Investment Casting.
Advanced methods for manufacturing high quality parts should be used to ensure the production of competitive products for the world market. Investment casting (IC) is a process where a wax pattern is used as a sacrificial pattern to manufacture high precision casting of solid metal parts. Rapid casting is in turn, a technique that eases the IC process by combining additive manufacturing (AM) technologies with IC. The use of AM technologies to create patterns for new industrial products is a unique opportunity to develop cost-effective methods for producing investment casting parts in a timely manner. Particularly, stereolithography (SLA) based AM is of interest due to its high dimensional accuracy and the smooth surface quality of the printed parts. From the first appearance of commercially available SLA printers in the market, it took a few decades until desktop SLA printers became available to consumers at a reasonable price. Therefore, the aim of this review paper is to analyze the state-of-the-art and applicability of SLA based 3D printing technology in IC manufacturing, as SLA based AM technologies have been gaining enormous popularity in recent times. Other AM techniques in IC are also reviewed for comparison. Moreover, the SLA process parameters, material properties, and current issues are discussed.


CD248: reviewing its role in health and disease.
CD248, also known as endosialin or tumor endothelial marker-1 (TEM-1), is a C-type lectin-like domain (CTLD) containing cell surface glycoprotein that is expressed by stromal cells of proliferating tissues during embryogenesis and postnatally in tumors and inflammatory lesions. Loss-of-function studies in mice support the notion that CD248 promotes tumor growth and inflammation, observations that are stimulating interest in evaluating this molecule as a therapeutic target. In spite of these advances, the mechanisms by which CD248 modulates cancer and inflammation remain largely enigmatic. This review highlights our current understanding of CD248, its structure, pattern of expression, regulation and function in various disease processes.


Excessive genomic DNA copy number variation in the Li-Fraumeni cancer predisposition syndrome.
DNA copy number variations (CNVs) are a significant and ubiquitous source of inherited human genetic variation. However, the importance of CNVs to cancer susceptibility and tumor progression has not yet been explored. Li-Fraumeni syndrome (LFS) is an autosomal dominantly inherited disorder characterized by a strikingly increased risk of early-onset breast cancer, sarcomas, brain tumors and other neoplasms in individuals harboring germline TP53 mutations. Known genetic determinants of LFS do not fully explain the variable clinical phenotype in affected family members. As part of a wider study of CNVs and cancer, we conducted a genome-wide profile of germline CNVs in LFS families. Here, by examining DNA from a large healthy population and an LFS cohort using high-density oligonucleotide arrays, we show that the number of CNVs per genome is well conserved in the healthy population, but strikingly enriched in these cancer-prone individuals. We found a highly significant increase in CNVs among carriers of germline TP53 mutations with a familial cancer history. Furthermore, we identified a remarkable number of genomic regions in which known cancer-related genes coincide with CNVs, in both LFS families and healthy individuals. Germline CNVs may provide a foundation that enables the more dramatic chromosomal changes characteristic of TP53-related tumors to be established. Our results suggest that screening families predisposed to cancer for CNVs may identify individuals with an abnormally high number of these events.


Relationship between 17-hydroxyprogesterone responses to human chorionic gonadotropin and markers of ovarian follicle morphology in women with polycystic ovary syndrome.
Women with polycystic ovary syndrome (PCOS) have increased 17-hydroxyprogesterone (17-OHP) responses to gonadotropin stimulation although individual variability is substantial, as reflected by exaggerated as well as normal responses. The relationship between 17-OHP responses to gonadotropin stimulation and markers of ovarian function has not been assessed. To determine whether 17-OHP responses are associated with antral follicle count (AFC), anti-Mullerian hormone (AMH), or inhibin B (Inh B) levels in PCOS and normal women. Prospective study. Research center at an academic medical center. Women with PCOS (n = 18) and normal controls (n = 18). Blood samples were obtained before and 24 hours after administration of 25 μg recombinant-human chorionic gonadotropin. Ovarian imaging was conducted with three-dimensional pelvic ultrasound. Basal and stimulated levels of 17-OHP, androgens, estrogen, AMH, Inh B, and AFC. In women with PCOS, 17-OHP responses were heterogeneous and inversely correlated with AMH and Inh B levels, but not AFC. In a subgroup of PCOS women with exaggerated 17-OHP responses, AMH levels were equivalent to that of normal women. In PCOS women with normal 17-OHP responses, AMH levels were markedly elevated. Based on heterogeneous 17-OHP responses to human chorionic gonadotropin in women with PCOS, AMH levels are inversely linked to ovarian androgen production while positively correlated with AFC. These findings suggest that in PCOS, AMH production may reflect redistribution of the follicle population or regulation by intraovarian mechanisms.


A perfect X-ray beam splitter and its applications to time-domain interferometry and quantum optics exploiting free-electron lasers.
X-ray free-electron lasers (FELs) deliver ultrabright X-ray pulses, but not the sequences of phase-coherent pulses required for time-domain interferometry and control of quantum states. For conventional split-and-delay schemes to produce such sequences, the challenge stems from extreme stability requirements when splitting Ångstrom wavelength beams, where the tiniest path-length differences introduce phase jitter. We describe an FEL mode based on selective electron-bunch degradation and transverse beam shaping in the accelerator, combined with a self-seeded photon emission scheme. Instead of splitting the photon pulses after their generation by the FEL, we split the electron bunch in the accelerator, prior to photon generation, to obtain phase-locked X-ray pulses with subfemtosecond duration. Time-domain interferometry becomes possible, enabling the concomitant program of classical and quantum optics experiments with X-rays. The scheme leads to scientific benefits of cutting-edge FELs with attosecond and/or high-repetition rate capabilities, ranging from the X-ray analog of Fourier transform infrared spectroscopy to damage-free measurements.


Effect on mortality and reinfarction of adding fruits and vegetables to a prudent diet in the Indian experiment of infarct survival (IEIS).
The effects of antioxidant-rich foods as adjuncts to a prudent diet were compared for 12 weeks in a randomized, single-blind and controlled trial in 204 (group A) and 202 (group B) patients with acute myocardial infarction. There was a significant decrease in cardiac end points in group A compared to group B (37 vs 58, p < 0.01) after 12 weeks. Within intervention group A, those 108 patients with greater adherence to the intervention program showed a greater reduction in cardiac end points (14 vs 58, p < 0.001), and a significant decrease in total mortality (6 vs 28, p < 0.001), including cardiac mortality (6 vs 25, p < 0.01) compared to group B. Underlying these beneficial effects, antioxidant-rich foods caused a significantly smaller rise in lactate dehydrogenase (LDH) cardiac enzyme in group A than in group B (427.8 vs 561.6 IU/dL), indicating that the protective influence of such a diet may be observed within 1 week. The subset of group A patients showing reduction in mortality also had a lesser rise in LDH and greater reduction in blood lipids, blood glucose and blood pressures. Antioxidant-rich foods also caused a significant decrease in blood lipids with a lower decrease in high-density lipoprotein cholesterol in group A than in group B. Assay of serum level of antioxidants and long-term follow-up may confirm our observations.


[Hybrid revascularization].
To evaluate our initial experience in the combination of two less invasive procedures for myocardial revascularization, coronary artery bypass grafting without cardiopulmonary bypass and immediate posterior angioplasty, on untreated lesions (hybrid revascularization) as an alternative treatment to conventional surgery in selected patients. From october 1996 to September 1998, 19 patients received hybrid revascularization. The mean age was 64 (47-76). Two patients underwent urgent surgery. Two patients had left main coronary disease, and 9 three-vessel disease. In general, we considered this procedure for patients with high-risk factors for cardiopulmonary bypass and two or more vessel disease. The internal mammary artery was connected to the left anterior descending artery in all 19 patients. All patients were moved to the hemodynamic ward immediately after surgery in 7 cases and before 48 h in the rest, 24 angioplasties were performed. A mean of 2.6 vessels per patient were revascularized and revascularization was complete in 15 patients (79%). One patient had perioperative myocardial infarction. There was no hospital mortality. Length of stay in the intensive care unit was 44 h (IQR = 49) and global postoperative stay was 8 days (IQR = 3.5). In the postoperative angiographic study, before the angioplasty, 95% of mammary arteries (CI 95% 74-100%) and 100% of saphenous grafts (CI 95% 59-100%) were patent. Combined revascularization allows almost complete revascularization, avoiding complications of cardiopulmonary bypass and minimizing surgical aggression. At the same time, it secures the graft of internal mammary artery to left anterior descending artery.


IL-17F Gene rs763780 and IL-17A rs2275913 Polymorphisms in Patients with Periodontitis.
Background: Periodontitis (PD) is a chronic inflammatory disease that can eventually lead to tooth loss. Genetic and environmental factors such as smoking are involved in the pathogenesis of PD. The development of PD is potentiated by various pathogens that induce an immune response leading to the production of cytokines, such as interleukin (IL)-17. The synthesis of IL-17 is influenced genetically. The polymorphisms in IL-17 gene may affect the synthesis of IL-17. The aim of this study was to examine the association between the IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in non-smoking and smoking patients to check if these polymorphisms could be a risk factor for PD. Methods: The study enrolled 200 patients with PD (130 non-smokers and 70 smokers) and 160 control subjects (126 non-smokers and 34 smokers). Periodontitis was diagnosed on the basis of 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. All samples were genotyped using allelic discrimination assays with TaqMan® probes on a Real-Time PCR Detection System. Results: There were no statistically significant differences in the distribution of the IL-17F rs763780 and IL-17A rs2275913 genotypes and alleles between patients with PD and control subjects, between smoking patients with PD and smoking control subjects, and between non-smoking patients with PD and non-smoking control subjects. Conclusions: The results of this study suggest a lack of statistically significant associations between IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in Polish population.


Influence of different erythrocyte storage times on the macrophage response in haemorrhagic shock mice.
To investigate the characteristics of the macrophage response to transfusion of erythrocytes kept at different storage times in the mouse model of haemorrhagic shock. Erythrocytes were isolated from mice and stored for 7, 21 or 35 days and samples injected intravenously into haemorrhagic shock mice. Changes in macrophages, inflammatory cytokines and T cell differentiation were assessed using flow cytometry or enzyme-linked immunosorbent assay (ELISA). In a second experiment, haemorrhagic shock mice were injected with 21D-erythrocytes and the expression of nuclear factor erythroid 2 p45-related factor 2 (Nrf2), arginine -1 (Arg-1) and inducible nitrous oxide (iNOS) determined. The proportion of M1-polarized macrophages was greatest in the 21D group while M2 macrophages tended to increase with the erythrocyte storage time. Levels of inflammatory cytokines and T helper 1 (Th1) cells increased in proportion to erythrocytes storage time. Most regulatory T cells (Treg) were found at 21D. Arg-1 expression was significantly increased in a group that received an heme oxygenase 1 (HO-1) agonist and significantly decreased in a group that received an HO-1 inhibitor but there were no differences in the expression of iNOS or Nrf2. 21D storage time may be an important time point for erythrocyte storage and immunity response and Arg-1 may have a role in the macrophage response to erythrocyte infusion.


Immobilized horse liver alcohol dehydrogenase as an on-line high-performance liquid chromatographic enzyme reactor for stereoselective synthesis.
Horse liver alcohol dehydrogenase (HLADH) has been non-covalently immobilized on an immobilized artificial membrane (IAM) high-performance liquid chromatography (HPLC) stationary phase. The resulting IAM-HLADH retained the reductive activity of native HLADH as well as the enzyme's enantioselectivity and enantiospecificity. HLADH was also immobilized in an IAM HPLC stationary phase prepacked in a 13 x 4.1 mm ID column to create an immobilized enzyme reactor (HLADH-IMER). The reactor was connected through a switching valve to a column containing a chiral stationary phase (CSP) based upon p-methylphenylcarbamate derivatized cellulose (Chiralcel OJR-CSP). The results from the combined HLADH-IMER/CSP and chromatographic system demonstrate that the enzyme retained its activity and stereoselectivity after immobilization in the column and that the substrate and products from the enzymatic reduction could be transferred to a second column for analytical or preparative separation. The combined HLADH-IMER/CSP system is a prototype for the preparative on-line use of cofactor-dependent enzymes in large-scale chiral syntheses.


Synthesis of furano[2,3-c]pyran-3-one and thieno[2,3-c]pyran-3-one derivatives through the coupling of 3-alkynyl-2-heteroaromatic carboxaldehydes with Fischer carbene complexes: total synthesis of a Baccharis-derived cadinene derivative.
The coupling of Fischer carbene complexes with 3-alkynyl-2-heteroaromatic carboxaldehyde derivatives has been examined. The reaction affords pyrones fused to furans or thiophenes in a single step. The compounds are stable enough for isolation. If the carbene complex features a remote alkene substituent, a subsequent Diels-Alder reaction can occur. This reaction has been used as the key step in the synthesis of a naturally occurring cadinene derivative.


Long-term follow-up of left ventricular thrombus after acute myocardial infarction. A two-dimensional echocardiographic study in 96 patients.
To determine the incidence, natural history, and relation to anticoagulant therapy of left ventricular thrombus (LVT) following acute myocardial infarction (MI), we performed two-dimensional echocardiography in 96 consecutive patients with isolated MI during the acute episode and after four and 12 months. Only patients with anterior MI received oral anticoagulant therapy on admission and throughout the study period. The LVT was identified in 21/65 patients with anterior and in 1/31 patients with inferior MI. The large majority of LVT cases were seen for the first time during the acute phase of MI. LVT was associated with a significantly higher peak value of CK-MB (118 +/- 24 vs 76 +/- 35, p less than 0.001) and Killip class (2.5 +/- 0.8 vs. 1.5 +/- 0.7, p less than 0.002). Patients with anterior MI and LVT more frequently had segmental dyskinesia during acute MI than patients without LVT (86 percent vs 18 percent, p less than 0.001). In four patients LVT resolved during the study period. Discontinuation of anticoagulant therapy in four patients with an aneurysm led to LVT formation in three. Two patients suffered a clinically recognized embolic event; one never had LVT demonstrated by echocardiography. Thus, LVT usually develops in the early days following large anterior MI, complicated by pump failure and segmental dyskinesia, even when patients receive oral anticoagulant therapy. Surprisingly, the incidence of embolic events was low (1/22) in our LVT patients.


Proteoglycan synthesis and content in articular cartilage and cartilage repair tissue in horses.
Hexosamine concentration, DNA concentration, and [35S]sulfate incorporation for articular cartilage obtained from various sites in the metacarpophalangeal and carpal joints of horses were measured. The same measurements were made on the repair tissue filling full-thickness articular defects in the intermediate carpal bone and on cartilage surrounding partial-thickness defects 6 weeks after the defects were created arthroscopically. Cellularity (measured as DNA concentration), proteoglycan content (measured as hexosamine concentration), and proteoglycan synthesis (measured as [35S]sulfate incorporation) varied according to the site sampled. Cartilage from the transverse ridge of the head of the third metacarpal bone and the radial facet of the third carpal bone had the lowest hexosamine concentration, whereas rate of proteoglycan synthesis was lowest in cartilage from the transverse ridge of the head of the third metacarpal bone and the distal articular surface of the radial carpal bone. Repair tissue filling a full-thickness cartilage defect at 6 weeks was highly cellular. It was low in proteoglycan content, but was actively synthesizing these macromolecules. In contrast, the cartilage surrounding a partial-thickness defect was unchanged 6 weeks after the original defect was made.


Crosstalk between SUMOylation and ubiquitylation controls DNA end resection by maintaining MRE11 homeostasis on chromatin.
DNA end resection is delicately regulated through various types of post-translational modifications to initiate homologous recombination, but the involvement of SUMOylation in this process remains incompletely understood. Here, we show that MRE11 requires SUMOylation to shield it from ubiquitin-mediated degradation when resecting damaged chromatin. Upon DSB induction, PIAS1 promotes MRE11 SUMOylation on chromatin to initiate DNA end resection. Then, MRE11 is deSUMOylated by SENP3 mainly after it has moved away from DSB sites. SENP3 deficiency results in MRE11 degradation failure and accumulation on chromatin, causing genome instability. We further show that cancer-related MRE11 mutants with impaired SUMOylation exhibit compromised DNA repair ability. Thus, we demonstrate that MRE11 SUMOylation in coordination with ubiquitylation is dynamically controlled by PIAS1 and SENP3 to facilitate DNA end resection and maintain genome stability.


Fine needle aspiration biopsy in patients with diffusely enlarged spleens.
To evaluate the diagnostic value and potential risk of fine needle aspiration biopsy (FNAB) of the spleen in patients with diffuse splenomegaly due to an undetermined cause. Retrospective evaluation of the medical records and cytologic material from 58 patients on whom FNAB was performed between 1967 and 1993. Sixty-five FNABs were performed on 58 patients. Lymphoproliferative diseases were found in six; in four additional cases, metastatic adenocarcinoma, sarcoidosis, Candida albicans and enterococcal infection were demonstrated. The remaining 55 biopsies either showed normal splenic tissue or were nondiagnostic. No complications were recorded. Splenic FNAB may be useful in some patients with diffuse splenomegaly. The diagnostic yield is rather low. The procedure, however, is simple, safe and well tolerated.


Steroidal and pregnane glycosides from the rhizomes of Tacca chantrieri.
The rhizomes of Tacca chantrieri have been analyzed as part of a systematic study on saponin constituents of medicinal plants. This has resulted in the isolation of three new bisdesmosidic furostanol saponins (1-3), two new bisdesmosidic pseudofurostanol saponins (4, 5), and two new pregnane glycosides (6, 7). Their structures were determined on the basis of extensive spectroscopic studies and a few chemical transformations.


Delayed development of toxic shock syndrome following abdominal tissue expansion in a pediatric reconstruction patient: case report.
Toxic shock syndrome (TSS) is a potentially fatal postoperative complication, and even more so if the diagnosis is delayed. We present the case of a 7-month-old male infant who developed TSS as a complication of tissue expansion using an external port device. There have been 5 documented cases of TSS after tissue expander or breast prosthesis placement occurring in the adult population, however, there has not been a reported case of TSS in an infant. The long interval to development of TSS like symptoms, 4 months in this case, should not exclude TSS from the differential diagnosis. In a pediatric patient, a diffuse macular rash without the severe systemic symptoms on initial presentation can present as a diagnostic challenge. New diagnosis techniques are discussed that can shorten the time to a diagnosis of TSS. In this case, because the local bacterial count was low, the expanded tissue was transferred without complication.


[Application of direct amplification with PowerPlex 16 HS system for detection of DNA in conventional evidence materials].
To study the effectiveness of direct amplification with PowerPlex 16 HS system for DNA detection in three conventional materials: fresh blood, oral swab, and cigarette butt. The genetic data of 11 samples of fresh blood, 10 samples of oral swab and 10 samples of cigarette butts were analyzed with PowerPlex 16 HS kit. The result was statistically analyzed. Success rate of whole genetic map test in fresh blood and oral swab samples was 100%. Success rate in cigarette butt samples was 90%. Direct amplification with PowerPlex 16 HS system is effective method to three types of conventional evidence material including fresh blood, oral swab and cigarette butt.


Introduction of a Hexalysine (6 K) Tag Can Protect from N-Terminal Cleavage and Increase Yield of Recombinant Proteins Expressed in the Periplasm of E. coli.
Recombinant expression of proteins in the periplasm of E. coli is frequently used for proteins containing disulfide bonds that are essential for protein folding and activity, as the cytosol of E. coli constitutes a reducing environment. The periplasm in contrast is an oxidative environment which supports proper protein folding. However, yields can be limited compared with cytoplasmic expression, and protocols must be adjusted to avoid overloading the periplasmic transportation machinery. Another less-appreciated issue with periplasmic expression is the potential generation of unwanted N-terminal cleavage products, a persistent issue which we encountered when expressing the disulfide bond containing extracellular regions of several Helicobacter pylori adhesins (BabA, BabB, BabC, and LabA) in the periplasm of E. coli XL10 GOLD, a strain traditionally not used for proteins expression. Here, we describe how introducing a C-terminal hexa-lysine (6 K) tag enhanced solubility and protected BabA from N-terminal proteolytic degradation (BabA), enabling crystallization and subsequent X-ray structural analysis. However. the same strategy had no advantageous effect for LabA, which using this protocol could be retrieved from the periplasm in relatively high yields (20-40 mg/L).


Holmium Intraductal Laser Lithotripsy of Biliary Stones in Liver Grafts.
Biliary stones after liver transplantation (LT) rarely occur but a focus on those complications and their treatment is needed. In total, 390 adult patients who underwent an LT from July 2004 to July 2014 entered the study. Biliary complications and notably biliary stones after LT were identified. In total, 365 LT were analyzed. Biliary stones were identified in 14 patients (3.8%). Predictive factors for the onset of biliary stones after LT were hepatocellular diseases (P = .038; OR = 9.7) and biliary stenosis (P = .000; OR = 11.9). Treatments consisted of percutaneous transhepatic procedures (4 patients), endoscopic retrograde procedures (9 patients), and in open surgery (1 case); in 2 cases, due to a failure of previous treatments, holmium intraductal laser lithotripsy (HILL) was used: the first patient, a 35-year-old woman developed multiple intrahepatic biliary stones after LT. Percutaneous transhepatic cholangiography (PTC) was ineffective and a HILL was performed, clearing the right common bile duct but leaving residual stones in the left duct. The patient underwent a retransplantation due to recurrent hepatitis C virus infection but died 3 months later because of graft failure. The second patient, a 42-year-old 14 years after retransplantation, developed biliary sludge and stones; after several attempts with PTC and endoscopic retrograde cholangiopancreatography, a HILL was performed. All stones except one big one were treated. The patient is alive and well. When usual treatments are unsuccessful and biliary stones are large, their fragmentation and treatment could be done with HILL, a promising procedure after LT.


Design and evaluation of a ZP3 peptide vaccine in a homologous primate model.
The concept of a safe, immunocontraceptive vaccine using the zona pellucida glycoprotein 3 (ZP3) as an immunogen has been marred by the appearance of ovarian dysfunction in several species. However, careful selection of epitopes on mouse ZP3 have demonstrated that it is possible to segregate contraceptive bone marrow-derived (B)-cell epitopes from the cytotoxic thymus-derived (T)-cell epitopes thought to be responsible for inducing ovarian disease. B-cell epitopes on marmoset ZP3 (mstZP3) were identified by epitope mapping studies. Using a panel of polyclonal antibodies against recombinant mstZP3, an immunodominant epitope mstZP3(301-320) was identified. A chimeric peptide was co-linearly synthesized incorporating this sequence with a promiscuous tetanus toxoid T-helper cell epitope. Using the common marmoset (Callithrix jacchus) as an animal model, we have compared the consequences of active immunization with homologous recombinant mstZP3 and mstZP3(301-320) chimeric peptide vaccine. Long-term infertility was achieved using mstZP3 but at the expense of ovarian function. In contrast, no disruption to ovarian function was observed following mstZP3(301-320) immunization. Antibodies to this peptide immunolocalized to the zona pellucida of both marmoset and human ovarian sections and inhibited human sperm-zona binding by approximately 60% in vitro. However, in-vivo studies indicated that targeting a single ZP3 epitope was insufficient to reliably and consistently achieve a contraceptive effect.


Equine sarcoids. A clinical and epidemiological study in relation to equine leucocyte antigens (ELA).
Associations between clinical parameters of sarcoids and the equine leucocyte antigen system (ELA) were analysed for 120 Swedish horses. Median age of affected horses was 5.2 years, and the majority presented with solitary tumors between 2 and 5 cm in diameter and ventral abdomen was a predilection site. Clinical signs first appeared at a median age of 3.5 years, and sarcoids at different locations first appeared at different ages. Lesions at different sites differed in size, and multiple tumors, early onset, long duration, and older age all had an association with large size. Clinical manifestations of sarcoids and the association between certain ELA-specificities and early onset (A5) and increased recurrence rates after surgery (W13), in addition to increased prevalence (A3W13), strengthen further that some horses are inherently predisposed to sarcoid growth. Unassociated with any clinical parameters, one third of the untreated horses became free of sarcoids due to "spontaneous" regression, perhaps as a result of immune responses against the tumors. Seventy percent of the horses were treated (mostly by excision), and large size was the main parameter promoting treatment. Excision had no significant effect on possibly remaining sarcoids. Recurrence rate after first treatment was about 35%, with the majority of tumors recurring within 4 months. Early onset, long duration, large size, and localization to distal limbs all appeared to increase risk of recurrence. Early treatment, performed under general anesthesia in recumbency which permits wide excision and measures to avoid autoinoculation, significantly reduced recurrence rates.


Socio-economic factors, mood, primary care utilization, and quality of life as predictors of intervention cessation and chronic stress in a type 2 diabetes prevention intervention (PREVIEW Study).
Sedentary lifestyle and unhealthy diet combined with overweight are risk factors for type 2 diabetes (T2D). Lifestyle interventions with weight-loss are effective in T2D-prevention, but unsuccessful completion and chronic stress may hinder efficacy. Determinants of chronic stress and premature cessation at the start of the 3-year PREVIEW study were examined. Baseline Quality of Life (QoL), social support, primary care utilization, and mood were examined as predictors of intervention cessation and chronic stress for participants aged 25 to 70 with prediabetes (n = 2,220). Moderating effects of sex and socio-economic status (SES) and independence of predictor variables of BMI were tested. Participants with children, women, and higher SES quitted intervention earlier than those without children, lower SES, and men. Lower QoL, lack of family support, and primary care utilization were associated with cessation. Lower QoL and higher mood disturbances were associated with chronic stress. Predictor variables were independent (p ≤ .001) from BMI, but moderated by sex and SES. Policy-based strategy in public health should consider how preventive interventions may better accommodate different individual states and life situations, which could influence intervention completion. Intervention designs should enable in-built flexibility in delivery enabling response to individual needs. ClinicalTrials.gov Identifier: NCT01777893.


Water sorption properties of HM-pectin and liposomes intended to alleviate dry mouth.
Pharmaceutical formulations intended for treatment of xerostomia (dry mouth) should be able to keep the oral mucosa hydrated for a prolonged period of time. The products already existing on the market contain water-soluble polymers, however their ability to moisturize the oral mucosa for a longer period of time seems limited. In this paper the sorption properties of water vapor of high-methoxylated pectin (HM-pectin, a hydrophilic biopolymer) and phosphatidylcholine-based (Soya-PC) liposomes have been studied and compared using a gravimetric method. The kinetics of water desorption and sorption have been recorded over the relative humidity range RH=95-0-95%, at 35°C. The obtained isotherms were found to be well described by the n-layer Brunauer-Emmet-Teller (BET) adsorption model. The water isotherms on HM-pectin were Type II (IUPAC), while water isotherms on liposomes were Type III. The maximum water sorption capacity of liposomes (1.2mg water per mg of adsorbent at 95% RH) was found to be twice as high as for pectin. Due to the slower water release from the liposomes, as well as their high water sorption capacity, they seem to have great potential in relieving the symptoms of dry mouth syndrome.


Can periodontal measures assist in the identification of adults with undiagnosed hyperglycaemia? A systematic review.
The aim of this review was to answer the following question: Can periodontal measures be used to identify dental patients with undiagnosed hyperglycaemia? Systematic searches of electronic databases and the grey literature were carried out to identify studies developing and/or validating prediction models, based on any periodontal measure, to screen adults for undiagnosed hyperglycaemia (pre-diabetes and diabetes). Risk of bias was evaluated using the PRediction mOdel risk-of-Bias ASsessment Tool (PROBAST). Ten studies were identified, of which eight were model development studies. The remaining two studies reported the external validation of one existing prediction model. The periodontal prediction model with some evidence of external validation showed moderate diagnostic performance in the development sample but lower performance in the external validation samples. According to PROBAST, all studies had high risk of bias mainly due to methodological limitations in data analysis, but also in the recruitment of participants, choice and measurement of periodontal predictors and diabetes. There is a need for more robust external validation studies of existing prediction models adhering to current recommendations. Dental professionals who see patients at risk of diabetes and routinely collect periodontal measures have an important role to play in their identification and referral.


Deregulated MIR335 that targets MAPK1 is implicated in poor outcome of paediatric acute lymphoblastic leukaemia.
Acute lymphoblastic leukaemia (ALL) is the most common paediatric malignancy. Although 90% of patients are now long-term survivors, the remaining 10% have poor outcome predominantly due to drug resistance. In this study, we carried out genome-wide microRNA (miRNA) microarray analysis on diagnostic bone marrow samples to determine miRNA expression profiles associated with poor outcome in ALL. A reduced expression of MIR335 was identified as the most significant miRNA abnormality associated with poor outcome. It is well known that glucocorticoid (GC) resistance is one of the major reasons contributing to poor outcome. We show that exogenous expression of MIR335 in ALL cells increases sensitization to prednisolone-mediated apoptosis. Moreover, we demonstrate that MAPK1 is a novel target of MIR335, and that MEK/ERK inhibitor treatment enhanced prednisolone-induced cell death through the activation of BIM (BCL2L11). These results provide a possible underlying molecular mechanism to explain the association between reduced MIR335 with poor clinical outcome, and suggest that approaches to re-introduce MIR335 expression or override MAPK1 activity may offer promising therapeutic strategies in the treatment of ALL.


Geriatricians and care homes: perspectives from geriatric medicine departments and primary care trusts.
Older people in care homes are clinically complex and particularly vulnerable to the effects of poor care and poor medicine. They are also a group to whom the NHS seems least committed. Geriatricians have become disengaged over the past two decades, as a result of social policies rather than clinical judgements. In 2000, the Royal College of Physicians, with the Royal College of Nursing and the British Geriatrics Society, issued guidance and recommendations for improving clinical practice. This paper reports progress since then based on results of national surveys of geriatric medicine departments and primary care trusts in England. The results show that important deficiencies persist, though most respondents were in favour of greater specialist involvement. Some suggestions are made for ways to improve the shared care of residents in care homes.


Stimulation of persisting colonies in agar cultures by sera from patients with CML and AML.
Cord plasma contains colony-stimulating activity (CSA) which stimulates the in vitro clonal growth of neutrophils, eosinophils, macrophages, erythrocytes, and persisting mast cells in semisolid cultures. Analysis of day 35 colonies in agar cultures was found to be a suitable means of demonstrating this activity and discriminating between it and granulocyte-macrophage colony-stimulating factor (GM-CSF). Serum (10%) from patients with acute and chronic myeloid leukemia (AML and CML) was added to normal human bone marrow cultures to search for similar activity in these patient's serum. Although the number of colonies on day 12 (predominantly neutrophils and macrophages) was not significantly different from the number of colonies in cultures containing normal serum, the number of colonies increased 500% in cultures containing CML serum on day 35. Serum from patients with AML during regeneration also stimulated an increased number of colonies on day 35. Although both eosinophil and mast cell colonies were still present on day 35, only mast cell colonies persisted for 150 days. On day 35, cultures containing 10% CML serum contained predominantly eosinophil colonies (84%), whereas cultures containing AML serum contained predominantly mast cell colonies (76%). Although serum contains various CSFs, the specific factor which stimulates persisting mast cell colonies may be the human equivalent of murine persisting (P) cell-stimulating factor (Multi-CSF).


Endoscopic needle aspiration cytology: a new method for the diagnosis of upper gastrointestinal cancer.
A technique for obtaining needle aspiration cytology specimens from upper gastrointestinal lesions at endoscopy is described. The validity of the technique was initially confirmed by applying it to resected gastric carcinomas. Thirty seven endoscopically visualised lesions were then sampled by forceps biopsy, brush and needle cytology. Ten lesions were subsequently found to be carcinomas. Needle aspiration produced identifiable malignant cells from seven of these lesions. In two it was the only sampling method which provided the correct diagnosis. This technique may be a useful addition to conventional endoscopic sampling methods, particularly where tumours lie deep to normal mucosa, or necrotic slough.


Antepartum reversible cerebral vasoconstriction syndrome with pre-eclampsia and reversible posterior leukoencephalopathy.
Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by severe headache and diffuse segmental constriction of the cerebral arteries that resolves spontaneously within a few months. Pregnancy is one of the precipitating factors of RCVS and most of the reported cases occurred in the post-partum period. We report a case of RCVS that occurred in a pregnant women with pre-eclampsia during her antepartum period. A 34-year-old woman in full-term pregnancy presented with a severe and acute headache. Magnetic resonance angiography (MRA) showed multiple segmental constrictions of the cerebral arteries. Magnetic resonance imaging revealed a high-intensity lesion in the left occipital lobe, consistent with reversible posterior leukoencephalopathy syndrome, on fluid attenuated inversion recovery sequences. The case was also complicated by severe pre-eclampsia and the patient underwent emergency cesarean section. Although her symptoms resolved rapidly, MRA revealed new lesions of arterial constriction 4 days after onset. The vasoconstriction completely resolved on MRA after 10 days and the patient was discharged without neurological sequelae.


The ionic, electrical, and secretory effects of endogenous cyclic adenosine monophosphate in mouse pancreatic B cells: studies with forskolin.
Forskolin, an activator of adenylate cyclase, was used to study the effects of endogenous cAMP on the stimulus-secretion coupling in mouse pancreatic B cells. Forskolin produced a rapid, dose-dependent (0.05-50 microM) increase in islet cAMP, which was not influenced by the prevailing concentration of glucose and did not require extracellular Ca2+. At a nonstimulatory concentration of glucose (3 mM), a high concentration of forskolin (20 microM) barely doubled basal insulin release, marginally decreased 86Rb+ efflux from the islets, was without effect on the B cell membrane potential, and did not affect 45Ca2+ uptake (5 min). High concentrations of endogenously formed cAMP thus failed to mimic these early steps of the B cell response to glucose and other stimuli. At a threshold concentration of the sugar (7 mM), 5 microM forskolin slightly depolarized the B cell membrane, induced electrical activity (slow waves and spikes), stimulated 45Ca2+ uptake, and triggered insulin release. At a stimulatory concentration of glucose (10 mM), forskolin potentiated insulin release; half maximal and maximal effects were observed at 1 and 20 microM, respectively. Forskolin also increased the rate of 45Ca2+ and 86Rb+ efflux from islet cells, augmented 45Ca2+ uptake, and potentiated the electrical activity triggered by glucose in B cells. Its effects on insulin release, 45Ca2+ fluxes, and electrical activity were inhibited by omission of extracellular Ca2+ and/or Ca channels blockers. At a high concentration of glucose (25 mM), forskolin augmented the amplitude and the duration of the spikes occurring in the depolarized B cell membrane, slightly increased 45Ca2+ uptake, and potentiated insulin release. At threshold or stimulatory concentrations of glucose, endogenously formed cAMP can thus induce or enhance the Ca2+-dependent events normally triggered by the sugar. It is suggested that, besides its action on intracellular Ca stores, cAMP facilitates Ca2+ influx in B cells, by modulating the gating properties of the Ca channels.


EEG frequency patterns in the cat prepyriform cortex during sleep and waking.
The cellular populations in the prepyriform cortex are a primary processing station for sensory information from the olfactory bulb. These populations are also influenced from forebrain and other brain systems involved in behaviour. Recording electrodes can be precisely placed in this cortex compared to many other brain structures. This permits straddling the cortical superficial pyramidal cell layer with a bipolar recording configuration and the ability to obtain information about awake-vigilant and other state conditions from this brain structure. Methadone, a vigorously arousing drug in the cat, and a short acting barbiturate was administered to compare the differences of EEG patterns obtained during normal awake and sleep conditions. Fourier analysis was used in this study and combined with computer profiles of spectra to show time relationships of the state conditions in the cortex. Good separation of the spectra, between the major states in the cat, were observed using this technique for both natural and drug-induced changes.


Software-Defined Optimal Computation Task Scheduling in Vehicular Edge Networking.
With the development of smart vehicles and various vehicular applications, Vehicular Edge Computing (VEC) paradigm has attracted from academic and industry. Compared with the cloud computing platform, VEC has several new features, such as the higher network bandwidth and the lower transmission delay. Recently, vehicular computation-intensive task offloading has become a new research field for the vehicular edge computing networks. However, dynamic network topology and the bursty computation tasks offloading, which causes to the computation load unbalancing for the VEC networking. To solve this issue, this paper proposed an optimal control-based computing task scheduling algorithm. Then, we introduce software defined networking/OpenFlow framework to build a software-defined vehicular edge networking structure. The proposed algorithm can obtain global optimum results and achieve the load-balancing by the virtue of the global load status information. Besides, the proposed algorithm has strong adaptiveness in dynamic network environments by automatic parameter tuning. Experimental results show that the proposed algorithm can effectively improve the utilization of computation resources and meet the requirements of computation and transmission delay for various vehicular tasks.


Multisite reproducibility of the broth microdilution method for susceptibility testing of Nocardia species.
Antimicrobial susceptibility testing (AST) of clinical isolates of Nocardia is recommended to detect resistance to commonly used antimicrobial agents; such testing is complicated by difficulties in inoculum preparation and test interpretation. In this study, six laboratories performed repetitive broth microdilution testing on single strains of Nocardia brasiliensis, Nocardia cyriacigeorgica, Nocardia farcinica, Nocardia nova, and Nocardia wallacei. For each isolate, a total of 30 microdilution panels from three different lots were tested at most sites. The goal of the study was to determine the inter- and intralaboratory reproducibility of susceptibility testing of this group of isolates. Acceptable agreement (>90% agreement at ±1 dilution of the MIC mode) was found for amikacin, ciprofloxacin, clarithromycin, and moxifloxacin. After eliminating MIC values from single laboratories whose results showed the greatest deviation from those of the remaining laboratories, acceptable agreement was also found for amoxicillin-clavulanic acid, linezolid, minocycline, and tobramycin. Results showed unsatisfactory reproducibility of broth microdilution testing of ceftriaxone with N. cyriacigeorgica and N. wallacei, tigecycline with N. brasiliensis and N. cyriacigeorgica, and sulfonamides with N. farcinica and N. wallacei. N. nova ATCC BAA-2227 is proposed as a quality control organism for AST of Nocardia sp., and the use of a disk diffusion test for sulfisoxazole is proposed as a check of the adequacy of the inoculum and to confirm sulfonamide MIC results.


Endothelial cell morphology around graded stenoses of the dog common carotid artery.
Graded stenoses (40-64% diameter reduction) were applied to dog common carotid arteries under anesthesia, and 27 days later the poststenotic velocity field was examined using transcutaneous pulsed Doppler velocimetry. Following in situ fixation, endothelial cell area, shape and orientation was measured by digitizing endothelial cell outlines in scanning electron micrographs. Endothelial cell area in the vicinity of the stenosis throat (within +/- 1 diameter) was reduced. No relation to stenosis hemodynamics was apparent. Cell area was increased 5 diameters downstream; in this region, there was turbulence due to jet break up. Cells were maximally rounded at the stenosis throat and gradually returned to upstream elongation by 5 diameters downstream. There was a region of flow separation and low velocity recirculation between the stenosis and the site of maximum turbulence, thus, downstream cell rounding was associated with flow separation. Subdivision of the experiments into four stenosis grades revealed little variation of the pattern of morphology between groups. It is possible that this is related to flow limitation with increasing grade. Elongation of endothelial cells through the entrance of the stenosis was apparent in only four experiments. Poststenotic dilatation of greater than 12% external diameter increase was noted in only four out of the sixteen experiments. In general, the relation of cell elongation to shear stress is supported, but this relationship does not fully explain endothelial cell shape at a stenosis.


Evaluation of an enzyme-linked immunosorbent assay that measures rhinovirus-specific antibodies in human sera and nasal secretions.
Rhinovirus-specific antibodies have traditionally been detected by their ability to neutralise the homologous rhinovirus serotype in tissue culture. Recently, however, we have described an enzyme-linked immunosorbent assay that detects rhinovirus-specific antibodies in sera and nasal secretions [Barclay and Al-Nakib, 1987]. Here we describe an evaluation of the ELISA in a study involving 71 adult volunteers inoculated intranasally with human rhinovirus type 2 (HRV-2). Pre- and post-inoculation serum samples and pre-inoculation nasal washings were tested for the presence of HRV-2-specific antibodies by ELISA. Such antibodies were associated with protection against infection when present locally in nasal secretions, but when also present in the serum they were associated with protection against both infection and the development of illness. The antibody concentrations showed strong correlation with each other and with that of antibodies detected by the neutralisation test. Following HRV-2 infection, rises in HRV-2-specific IgA in sera detected by ELISA occurred more frequently than rises in neutralising antibody. These results suggest that the ELISA is a sensitive and reliable indicator of recent infection, as well as a predictor of homologous immune status.


Ankle sprains and fractures in adults.
The orthopaedic nurse will undoubtedly care for patients with ankle injuries. Ankle sprains and fractures are common injuries seen in orthopaedic practices in the United States. To provide comprehensive nursing care of these injuries, nurses should understand ankle biomechanics as well as anatomy. Knowledge of fracture classification schemes, pathology of injury, and treatment modalities is also important. Fracture classification schemes vary as do treatment modalities. Ankle sprains and fractures can be treated operatively or nonoperatively, and orthopaedic nurses play an important role in the care of patients with such ankle injuries.


[Lesions of the male breast].
Lesions of the male breast are rather rare. The most frequent lesion is gynecomastia followed by breast cancer. Gynecomastia is well known but male breast cancer is a rather rare tumor. It occurs in less than 1% of all cancers in men and of breast cancers. The mean age is high with a median of 68 years. Predisposing factors appear to be associated with hyperestrogenism such as testicular factors including maldescensus, orchitis and infertility. Other factors are Klinefelter, adipositas, diabetes mellitus and liver disease. In recent years an increased risk of male breast cancer has been reported in families with positive family history and in which BRCA2 mutations have been identified. Diagnostic procedures for male breast lesions should be the same as for the female breast. Underdiagnosis of male breast lesions is a frequently reported problem. Histology of male breast cancer differs in some aspects from female breast cancer. Male breast cancers are more frequently invasive ductal, G3 and steroid hormone receptor positive. In case of intraductal cancer male lesions are more frequently papillary. Lobular carcinomas almost never occur. Prognostic factors for male breast cancer are similar to female breast cancer. For male breast cancer no randomised therapy studies are described. Therefore all therapy strategies are extrapolated from female breast cancer. The existing main therapeutic problem is undertreatment.


Allosteric communication in cysteinyl tRNA synthetase: a network of direct and indirect readout.
Protein structure networks are constructed for the identification of long-range signaling pathways in cysteinyl tRNA synthetase (CysRS). Molecular dynamics simulation trajectory of CysRS-ligand complexes were used to determine conformational ensembles in order to gain insight into the allosteric signaling paths. Communication paths between the anticodon binding region and the aminoacylation region have been identified. Extensive interaction between the helix bundle domain and the anticodon binding domain, resulting in structural rigidity in the presence of tRNA, has been detected. Based on the predicted model, six residues along the communication paths have been examined by mutations (single and double) and shown to mediate a coordinated coupling between anticodon recognition and activation of amino acid at the active site. This study on CysRS clearly shows that specific key residues, which are involved in communication between distal sites in allosteric proteins but may be elusive in direct structure analysis, can be identified from dynamics of protein structure networks.


Effect of travel and rest on performance of professional basketball players.
We have studied 8,495 regular season games in the National Basketball Association over eight seasons (1987-1988 through 1994-1995) to analyze the effects of travel and rest on performance. We found that more time between games improved performance, an effect that was constant over time and statistically significant. More than 1 day between games increased the home team's score by 1.1 points and the visitor's by 1.6 points. Peak performance occurred with 3 days between games. The negative effects of little time between games may be due to lack of time for physical recovery, rather than any effects of circadian rhythm (jet lag). We found few consistent effects of distance traveled or direction of travel. We did find a suggestion of circadian rhythm effects in a subanalysis of games on either coast in which the visitor traveled across the country, while the home team did not travel (n = 101). In these games, the visiting team did four points better (p = 0.07) when they traveled west to east rather than east to west, almost nullifying the home-court advantage. This effect, like similar findings for Monday Night Football games, may be due to West Coast visitors playing night games at an earlier time according to their "internal clock". An incidental finding in our study was that the home-court advantage decreased over 8 years, from about six points to three points (due to relatively lower field-goal percentages and fewer free throws by the home team).


Patients' understanding of and adjustment to epilepsy: interim findings from a European survey.
The purpose of the study was to discover how much European patients with epilepsy and their carers understand about epilepsy. This article reports the interim results for the first four European countries recruited to the study and includes data collected from 1,920 people with epilepsy and 2,136 carers. Clinical and demographic details and data on understanding of epilepsy were collected using self-completed questionnaires mailed to members of epilepsy support groups. There were no significant differences between people with epilepsy and carers for scores on the Epilepsy Knowledge Questionnaire, although people with epilepsy were more likely to score in the higher ranges. Higher scorers on the questionnaire were more likely to be better educated, to have lower scores on the impact of epilepsy scales, to have higher scores on the adjustment to epilepsy scale, and were less likely to report feeling stigmatized. The study confirms the findings of previous studies that people with epilepsy are reasonably well informed, although some gaps in their knowledge were evident. A comparison of country differences will be made and multivariate statistical analysis will allow a better understanding of the contribution of knowledge to people's overall adjustment to their condition.


Immunohistochemical detection of components of the insulin-like growth factor system during skeletal muscle growth in the pig.
The insulin-like growth factor (IGF) system plays an important role in postnatal somatic and skeletal muscle growth in pigs. There is little information on the occurrence and distribution of components of the IGF system in postnatal porcine skeletal muscle. IGF-I, IGF receptor 1 (IGF1R) and the IGF-binding proteins IGFBP-1 and -3 in longissimus dorsi and triceps brachii were localized in muscle biopsies from 12 commercially crossbred pigs aged from 28 to 199 days as well as from the sire generation, by immunohistochemistry. Plasma IGF-I concentrations were also determined using radio-immunoassays. Unlike other species, IGF-I was localized in porcine skeletal muscle fibres. Staining intensity correlated with the highest plasma IGF-I levels and phases of intensive muscle growth from the 11th to 22nd week. The pattern of IGF1R immunostaining, which was strong, correlated with that of IGF-I, IGF1R was also localized in endomysial tissues. IGFBP-1 was not detected within muscle fibres, but was found in the endomysium and vessel walls, while IGFBP-3 was localized with IGF-1 and its receptor. Higher magnification revealed that IGF1R, IGFBP-3 and probably IGF-I appeared in the tubular system. Inhibitory as well as stimulating controls of IGFBP-1 and -3 on IGF functions are discussed, which may maintain a balance between autocrine growth promoting activities of IGF-I and IGF1R.


Dose tolerance and pharmacokinetic studies of L (+) pseudoephedrine capsules in man.
Dose tolerance and pharmacokinetic studies of pseudoephedrine sustained action capsules were performed in thirty-three adult male subjects who received either 120 mg or 150 mg capsules every twelve hours for seven consecutive days in a double-blind parallel design study. Although only one subject in the 150 mg group was discontinued prematurely from this study, a large number of side effects typical of CNS stimulation were seen. A placebo effect might account for a portion of these complaints, however symptoms evaluated as being due to drug were significantly more severe and persistent in the 150 mg group. Pulse rates showed a persistent and significant increase while systolic and diastolic blood pressure fell from the baseline values in both groups. A pharmacokinetic analysis of the pseudoephedrine plasma concentration-time data provided estimates of half-life and the volume of distribution/availability ratio. The values obtained were in good agreement with values reported by others. Half-life was not influenced by urine pH probably as a result of the narrow range of urine pHs observed in the subjects. Calculations of relative bioavailability suggest that the 120 mg capsule formulation has a 30% greater bioavailability compared to the 150 mg capsule.


Marijuana effect expectancies: relations to social anxiety and marijuana use problems.
High social anxiety is related to marijuana problems, yet the nature of this relation remains unclear. We examined relations between marijuana effect expectancies, social anxiety, and marijuana among undergraduates (N=337). Social anxiety was related positively to Negative Expectancies and negatively to Tension Reduction Expectancies. Among socially anxious individuals, greater belief that marijuana produces Cognitive and Behavioral Impairment was associated with greater marijuana use rates. Negative Expectancies mediated the social anxiety-marijuana problems link. These data provide new insight into problematic marijuana use among this high-risk group.


Timing of birth and risk of multiple sclerosis in the Scottish population.
Development of multiple sclerosis (MS) is believed to result from interplay of genes and environmental factors, which may be anticipated to act in a seasonal manner. Scotland has the highest prevalence of MS in the world. We aimed to determine if risk of multiple sclerosis is associated with season of birth in the Scottish population. Data for MS patients within the West of Scotland (n = 1,309) was obtained. Birth rates of MS patients were compared with national (n = 6,198,352) and regional (n = 664,447) controls. Excess MS births occur in the spring months, with 22% more than expected (401 observed vs. 328 expected, p < 0.0001). Peak month in both sexes was April. Fewer MS births occurred in autumn, with 16% fewer births compared with regional controls (275 observed vs. 328 expected, p = 0.01). Our study, the largest in the Scottish population, demonstrates season of birth and risk of MS are associated. Elucidating potential environmental factor(s) accounting for such an association remains a challenge.


Experimental estimation of mutation rates in a wheat population with a gene genealogy approach.
Microsatellite markers are extensively used to evaluate genetic diversity in natural or experimental evolving populations. Their high degree of polymorphism reflects their high mutation rates. Estimates of the mutation rates are therefore necessary when characterizing diversity in populations. As a complement to the classical experimental designs, we propose to use experimental populations, where the initial state is entirely known and some intermediate states have been thoroughly surveyed, thus providing a short timescale estimation together with a large number of cumulated meioses. In this article, we derived four original gene genealogy-based methods to assess mutation rates with limited bias due to relevant model assumptions incorporating the initial state, the number of new alleles, and the genetic effective population size. We studied the evolution of genetic diversity at 21 microsatellite markers, after 15 generations in an experimental wheat population. Compared to the parents, 23 new alleles were found in generation 15 at 9 of the 21 loci studied. We provide evidence that they arose by mutation. Corresponding estimates of the mutation rates ranged from 0 to 4.97 x 10(-3) per generation (i.e., year). Sequences of several alleles revealed that length polymorphism was only due to variation in the core of the microsatellite. Among different microsatellite characteristics, both the motif repeat number and an independent estimation of the Nei diversity were correlated with the novel diversity. Despite a reduced genetic effective size, global diversity at microsatellite markers increased in this population, suggesting that microsatellite diversity should be used with caution as an indicator in biodiversity conservation issues.


'Mend the bend': a report of two cases of labial dilacerated and palatal dilacerated crown.
Dilaceration is the result of a developmental anomaly in which there has been an abrupt change in the axial inclination between the crown and the root of a tooth. Crown dilaceration of permanent tooth occurs due to the non-axial displacement of the already formed hard tissue portion of the developing crown at an angle to their longitudinal axis due to trauma to the primary predecessors. Thus endo-aesthetic management of such teeth helps in maintaining morphology as well as aesthetics in a growing child. This article depicts two cases of severely dilacerated crown.


Development of a catheter for combined intravascular ultrasound and photoacoustic imaging.
Atherosclerosis is characterized by formation and development of the plaques in the inner layer of the vessel wall. To detect and characterize atherosclerotic plaques, we previously introduced the combined intravascular ultrasound (IVUS) and intravascular photoacoustic (IVPA) imaging capable of assessing plaque morphology and composition. The utility of IVUS/IVPA imaging has been demonstrated by imaging tissue-mimicking phantoms and ex vivo arterial samples using laboratory prototype of the imaging system. However, the clinical realization of a IVUS/IVPA imaging requires an integrated intravascular imaging catheter. In this paper, two designs of IVUS/IVPA imaging catheters--side fire fiber-based and mirror-based catheters--are reported. A commercially available IVUS imaging catheter was utilized for both pulse-echo ultrasound imaging and detection of photoacoustic transients. Laser pulses were delivered by custom-designed fiber-based optical systems. The optical fiber and IVUS imaging catheter were combined into a single device. Both designs were tested and compared using point targets and tissue-mimicking phantoms. The results indicate applicability of the proposed catheters for clinical use.


Early life adversity is associated with a smaller hippocampus in male but not female depressed in-patients: a case-control study.
Three studies assessed the association of early life adversity (ELA) and hippocampal volumes in depressed patients, of which one was negative and the two others did not control for several potential confounding variables. Since the association of ELA and hippocampal volumes differ in male and female healthy volunteers, we investigated the association of ELA and hippocampal volumes in depressed patients, while focusing specifically on sex and controlling for several relevant socio-demographic and clinical variables. Sixty-three depressed in-patients treated in a psychiatric setting, with a current Major Depressive Episode (MDE) and a Major Depressive Disorder (MDD) were included and assessed for ELA. Hippocampal volumes were measured with brain magnetic resonance imaging (MRI) and automatic segmentation. They were compared between patients with (n = 28) or without (n = 35) ELA. After bivariate analyses, multivariate regression analyses tested the interaction of sex and ELA on hippocampal volume and were adjusted for several potential confounding variables. The subgroups of men (n = 26) and women (n = 37) were assessed separately. Patients with ELA had a smaller hippocampus than those without ELA (4.65 (±1.11) cm3 versus 5.25 (±1.01) cm3), bivariate: p = 0.03, multivariate: HR = 0.40, 95%CI [0.23;0.71], p = 0.002), independently from other factors. This association was found in men (4.43 (±1.22) versus 5.67 (±0.77) cm3), bivariate: p = 0.006, multivariate HR = 0.23, 95%CI [0.06;0.82], p = 0.03) but not in women. ELA is associated with a smaller hippocampus in male but not female depressed in-patients. The reasons for this association should be investigated in further studies.


Laparoscopic en bloc resection of locally advanced colon cancer with involvement of the liver, small bowel, omentum, and abdominal wall.
Locally advanced colon cancer with the involvement of adjacent organs is treated radically with en bloc resection with negative margins. Laparoscopy is seldom recommended for such patients. Operative laparoscopic technique is presented for radical en bloc resection of locally advanced right colon cancer. The patient is a 56-year-old morbidly obese (body mass index 47) male, who was scheduled to undergo a routine laparoscopic right hemicolectomy and at exploration was found to have a large mass involving segments V and VI of the liver, small bowel, omentum, and abdominal wall. A laparoscopic-assisted en bloc resection was performed. The patient went home in 7 days. The tumor was staged as T4N0M0, American Joint Commission on Cancer stage IIb with 21 negative nodes. Laparoscopic resection for selected patients with locally advanced colonic neoplasms should be considered an option in tertiary referral centers.


Juvenile xanthogranuloma of the paravertebral soft tissue in infancy: a report of two cases.
We report 2 cases of paravertebral soft tissue lesions with the histologic features of juvenile xanthogranuloma, both of which occurred in infants. Juvenile xanthogranuloma situated in the soft tissue is rare. We describe 2 cases with similar clinical and pathologic features; there has been no recurrence at 1 and 2 years after excision, respectively.


The spatial learning phenotype of heterozygous leaner mice is robust to systematic variation of the housing environment.
Providing stimulation and allowing the performance of motivated behaviors through environmental enrichment improves learning and memory in rodents and delays cognitive impairment in neurodegenerative disease models. The leaner mutation affects the Ca(v)2.1 voltage-gated calcium channel alpha(1A)-subunit gene, and homozygous mice show severe phenotypic alterations. Although several authors have described heterozygous mice as normal, recent studies in our laboratory indicate motor and cognitive impairment in tg(la)/+ mice. In the present study, we evaluated whether this impairment is robust to systematic variation of the housing environment from barren to standard and furnished (enriched) cages. Wildtype (n = 55) and tg(la)/+ (n = 79) C57Bl/6J mice were assigned randomly to 1 of the 3 housing systems and tested on the Morris water maze at 6, 12, and 20 mo of age. The results confirmed impaired performance in tg(la)/+ mice, particularly in older mice. At 12 and 20 mo, only wildtype (and not tg(la)/+) mice showed evidence of learning (spending increased time in the target quadrant) during the probe trial. Housing also affected performance: at 12 mo, only mice from furnished cages showed evidence of learning, and in aged mice (20 mo), only those housed in more complex environments showed long-term memory (8 mo after previous testing) of the platform position. In conclusion, a heterozygous mutation in a Ca(2+) channel gene causes cognitive deficits in leaner mice that are robust to environmental variation but attenuated by physical and behavioral stimulation.


Kallmann syndrome: fibroblast growth factor signaling insufficiency?
Kallmann syndrome (KAL) is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Anosmia is related to the absence or hypoplasia of the olfactory bulbs. Hypogonadism is due to GnRH deficiency and is likely to result from the failed embryonic migration of GnRH-synthesizing neurons. These cells normally migrate from the olfactory epithelium to the forebrain along the olfactory nerve pathway. KAL is phenotypically and genetically heterogeneous. The gene responsible for the X-chromosome linked form of the disease (KAL1) has been identified in 1991. KAL1 encodes anosmin-1, an approximately 95-kDa glycoprotein of unknown function which is present locally in various extracellular matrices during the period of organogenesis. The recent finding that FGFR1 mutations are involved in an autosomal dominant form of Kallmann syndrome (KAL2), combined with the analysis of mutant mouse embryos that no longer express Fgfr1 in the telencephalon, suggests that the disease results from a deficiency in FGF signaling at the earliest stage of olfactory bulb morphogenesis. We propose that the role of anosmin-1 is to enhance FGF signaling and suggest that the gender difference in anosmin-1 dose (because KAL1 partially escapes X-inactivation) explains the higher prevalence of the disease in males.


Diagnostic Accuracy of Infection Markers to Diagnose Infections in Neonates and Children Receiving Extracorporeal Membrane Oxygenation.
Infections represent one of the most common complications in patients managed on Extracorporeal Membrane Oxygenation (ECMO) and are associated with poorer outcomes. Clinical signs of infection in patients on ECMO are non-specific. We assessed the diagnostic accuracy of Procalcitonin (PCT), C-reactive protein (CRP) and White cell count (WCC) to diagnose infection on ECMO. Retrospective single center observational study including neonates and children <18 years treated with ECMO in 2015 and 2016. Daily data on PCT, CRP and WCC were assessed in relation to microbiologically confirmed, and clinically suspected infection on ECMO using operating characteristics (ROC) curves. Sixty-five ECMO runs in 58 patients were assessed. CRP had the best accuracy with an area under the ROC curve (AUC) of 0.79 (95%-CI 0.66-0.92) to diagnose confirmed infection and an AUC of 0.72 (0.61-0.84) to diagnose confirmed and suspected infection. Abnormal WCC performed slightly worse with an AUC of 0.70 (0.59-0.81) for confirmed and AUC of 0.66 (0.57-0.75) for confirmed and suspected infections. PCT was non-discriminatory. The diagnosis of infections acquired during ECMO remains challenging. Larger prospective studies are needed that also include novel infection markers to improve recognition of infection in patients on ECMO.


PhRMA survey on the conduct of first-in-human clinical trials under exploratory investigational new drug applications.
The FDA guidance on exploratory IND studies is intended to enable sponsors to move ahead more efficiently with the development of promising candidates. A survey of PhRMA member companies was conducted in 2007 to obtain a cross-sectional industry perspective on the current and future utility of exploratory IND studies. About 56% of survey responders (9 companies of 16 survey responders) conducted or were planning to conduct clinical studies under exploratory INDs. The majority of microdosing studies are performed to characterize human pharmacokinetics or to examine target organ pharmacokinetics using PET imaging techniques. On the other hand, the majority of pharmacological end point studies conducted under exploratory IND are performed to determine whether the compound modulated its pharmacological target or to evaluate the degree of saturation of a target receptor. The present survey suggests that although the merits of exploratory INDs are still being debated, the diversity in the applications cited, the potential for early clinical guidance in decision making and the increasing pressure on containing drug development costs, suggest that the exploratory IND/CTA will be a valuable option with evolving and possibly more specific applications for the future.


Oxidative damage in the livers of senescence-accelerated mice: a gender-related response.
The prevalence of liver diseases emphasizes the need of animal models to research on the mechanism of disease pathogenesis. Furthermore, most of the liver pathologies have the oxidative stress as an important component. The senescence-accelerated mouse strain SAMP8 was proposed as a valuable animal model for the study of liver diseases. To gain a better understanding of the mechanisms underlying degenerative processes in SAMP8 mice livers, we studied the oxidative-induced damage in 5-month-old SAMP8 mice and SAMR1, senescence-accelerated-resistant mice. We found profound differences in the antioxidant response to aging between sexes, with males displaying lowest levels of main antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) in SAMP8; whereas females had no difference in their activities, except for GR, when compared with their SAMR1 controls. The results obtained show the binomial SOD/CAT as an important factor for counteracting reactive oxygen species-dependent damage. There were not pathological differences at the morphological level between both strains, although the decay in protection against free radicals had an immediate response by increasing lipid and protein oxidative damage in SAMP8 mice liver. At 5 months, both male and female SAMP8 mice confront the oxidative stress challenge to different extents. Indeed, proteins seem to be the most vulnerable biomolecule in SAMP8 male mice.


The anti-platelet effects of apocynin in mice are not mediated by inhibition of NADPH oxidase activity.
Apocynin, or a (myelo)peroxidase-derived product thereof, is a powerful inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Apocynin has also been shown to prevent aggregation of platelets in response to agonists such as collagen and thrombin. The aims of this study were to establish whether NADPH oxidase activity is required for aggregation of murine platelets to collagen and other agonists and whether the anti-aggregatory effects of apocynin are due to an inhibitory action against this enzyme. Washed platelets were isolated from male C57BL6 (wild-type), Nox2-deficient (Nox2(-/y )), and p47phox-deficient (p47phox(-/-)) mice for assessment of aggregation and NADPH oxidase subunit (Nox2, p47phox) expression. Collagen and U46619 elicited aggregation of murine platelets, and these responses were inhibited by apocynin at concentrations ≥100 μM. By contrast, aggregations to a direct protein kinase C activator, phorbol-12,13-dibutyrate, were insensitive to apocynin. Immunoblotting of platelet protein homogenates from wild-type mice with anti-Nox2 or p47phox antibodies revealed strong bands at 58 and 50 kDa, respectively. While expression of these immunoreactive bands was greatly diminished in platelets from Nox2(-/y ) and p47phox(-/-) mice, collagen still elicited aggregations that were similar to those observed in platelets from wild-types. Moreover, apocynin was an equally effective inhibitor of aggregation in platelets from all three mouse strains. In conclusion, these data suggest that NADPH oxidase-derived reactive oxygen species play no role in the aggregation response of washed murine platelets to collagen. Thus, our observation that apocynin is a powerful inhibitor of platelet aggregation raises further questions about the selectivity of this drug as an NADPH oxidase inhibitor.


Can Cancellara Really be a Flandrien? Ethno-Cultural Identity Representation Predicts Regional Exclusivity of a Historically Contested Cycling Term.
In Flanders the term flandrien refers to cyclists who display a strong work ethic, great perseverance, are powerful and who perform best in adverse weather conditions. Until the 1960s, only leading cyclists originating from the province of West- and East-Flanders were considered as flandriens. After 1960, the media extended the use of this term to Belgian cyclists in general and even to international cyclists. The present study examined whether Flemish citizens agree with this generalization considering that the term flandrien still plays a highly symbolical role in the public discourse on Flemish identity. First, the main aim was to investigate whether having an ethno-cultural identity representation of the Flemish identity is positively related to perceived regional exclusivity of the term flandrien. Second, this study explored whether Flemish identification moderates this relation (i.e. this relation is only expected for high identifiers) and also predicts Flemings' regional exclusivity of the term. Results revealed that the more Flemings endorse an ethno-cultural identity representation the more they consider a flandrien as an exclusively Flemish cyclist, and the less they will include international cyclists in their consideration of a flandrien. Flemish identification did not moderate this relation but did predict the consideration of a flandrien as a Flemish cyclist. These findings indicate that the current interpretation of the historical cycling term flandrien is influenced by cultural conceptualizations of Flemish identity.


Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Inhibitor as a Novel Therapeutic Tool for Lung Injury.
Pulmonary fibrosis is a progressive disease characterized by lung remodeling due to excessive deposition of extracellular matrix. In this study, the bleomycin experimental model of pulmonary fibrosis was employed to investigate the anti-fibrotic and immunomodulatory activity of the inhibition of MALT1 protease activity. Mice received a single intra-tracheal administration of bleomycin (1 mg/kg) in the presence or absence of MI-2, a selective MALT1 inhibitor, (a dose of 30 mg/kg administered intra-peritoneally 1 h after bleomycin and daily until the end of the experiment). Seven days after bleomycin instillation mice were sacrificed and bronchoalveolar lavage fluid analysis, measurement of collagen content in the lung, histology, molecular analysis and immunohistochemistry were performed. To evaluate mortality and body weight gain a subset of mice was administered daily with MI-2 for 21 days. Mice that received MI-2 showed decreased weight loss and mortality, inflammatory cells infiltration, cytokines overexpression and tissue injury. Moreover, biochemical and immunohistochemical analysis displayed that MI-2 was able to modulate the excessive production of reactive oxygen species and the inflammatory mediator upregulation induced by bleomycin instillation. Additionally, MI-2 demonstrated anti-fibrotic activity by reducing transforming growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and receptor associated factor 6 (TRAF6) expression. The underlying mechanisms for the protective effect of MI-2 bleomycin induced pulmonary fibrosis may be attributed to its inhibition on NF-κB pathway. This is the first report showing the therapeutic role of MALT1 inhibition in a bleomycin model of pulmonary fibrosis, thus supporting further preclinical and clinical studies.


Nickel-Copper-Catalyzed Hydroacylation of Vinylarenes with Acyl Fluorides and Hydrosilanes.
The hydroacylation of vinylarenes with acyl fluorides and hydrosilanes was enabled by a synergistic bimetallic Ni/Cu-catalytic system, giving access to the corresponding branched ketone products. The reaction takes place under mild conditions at 25-80 °C and tolerates base-sensitive functional groups such as methoxycarbonyl and acetoxy groups.


Tobacco and alcohol use in rural elderly Indian population.
Tobacco and alcohol use are serious health problems. Studies focusing on problems associated with tobacco and alcohol use in the elderly are limited. To find out the prevalence of tobacco and alcohol use among rural elderly population. This cross-sectional study was conducted in the intensive field practice area of the Comprehensive Rural Health Services Project in Ballabgarh in Faridabad, Haryana, a rural field practice area of the Centre for Community Medicine, All India Institute of Medical Sciences, New Delhi. The sample was selected using stratified random cluster sampling. The participants were >/=60 years of age at the time of interview. Data on tobacco and alcohol use pattern of 1117 elderly were collected during the interview. The prevalence of smoking was 71.8% in men (n=490) and 41.4% in women (n=497). Among men smokers, 41.5% were light smokers (</=5 beedis/day), 42.9% were moderate smokers (6-20 beedis/day) and 15.6% were heavy smokers (>20 beedis/day). Among women smokers, 71.8% were light smokers, 23.8% were moderate smokers and 4.4% were heavy smokers. Regular alcohol intake was seen in 16.3% of the men compared with 0.8% of the women. The finding of a high prevalence of smoking and alcohol consumption among men in this rural population of India is of serious concern and therefore needs remedial measures.