Using Transcriptome Analysis to Identify Genes Involved in Switchgrass Flower Reversion.
Floral reversion is a process in which differentiated floral organs revert back to vegetative organs. Although this phenomenon has been described for decades, the underlying molecular mechanisms remain unclear. In this study, we found that immature switchgrass (Panicum virgatum) inflorescences can revert to neonatal shoots when incubated on a basal medium with benzylaminopurine. We used anatomical and histological methods to verify that these shoots were formed from floret primordia through flower reversion. To further explore the gene regulation of floral reversion in switchgrass, the transcriptome of reversed, unreversed, and uncultured immature inflorescences were analyzed and 517 genes were identified as participating in flower reversion. Annotation using non-redundant databases revealed that these genes are involved in plant hormone biosynthesis and signal transduction, starch and sucrose metabolism, DNA replication and modification, and other processes crucial for switchgrass flower reversion. When four of the genes were overexpressed in Arabidopsis thaliana, vegetative growth was facilitated and reproductive growth was inhibited in transgenic plants. This study provides a basic understanding of genes regulating the floral transition in switchgrass and will promote the research of floral reversion and flower maintenance.


Cell adhesion molecules regulate fibrotic process via Th1/Th2/Th17 cell balance in a bleomycin-induced scleroderma model.
Mice s.c. injected with bleomycin, an experimental model for human systemic sclerosis, develop skin and lung fibrosis, which is mediated by inflammatory cell infiltration. This process is highly regulated by multiple adhesion molecules and does not require Ag sensitization. To assess the role of adhesion molecules in this pathogenetic process, bleomycin-induced fibrosis was examined in mice lacking adhesion molecules. L-selectin and/or ICAM-1 deficiency inhibited skin and lung fibrosis with decreased Th2 and Th17 cytokines and increased Th1 cytokines. In contrast, P-selectin deficiency, E-selectin deficiency with or without P-selectin blockade, or P-selectin glycoprotein ligand 1 (PSGL-1) deficiency augmented the fibrosis in parallel with increased Th2 and Th17 cytokines and decreased Th1 cytokines. Furthermore, loss of L-selectin and/or ICAM-1 reduced Th2 and Th17 cell numbers in bronchoalveolar lavage fluid, whereas loss of P-selectin, E-selectin, or PSGL-1 reduced Th1 cell numbers. Moreover, Th1 cells exhibited higher PSGL-1 expression and lower expression of LFA-1, a ligand for ICAM-1, whereas Th2 and Th17 cells showed higher LFA-1 and lower PSGL-1 expression. This study suggests that L-selectin and ICAM-1 regulate Th2 and Th17 cell accumulation into the skin and lung, leading to the development of fibrosis, and that P-selectin, E-selectin, and PSGL-1 regulate Th1 cell infiltration, resulting in the inhibition of fibrosis.


[Structural features of the excretory ducts of the palatal salivary glands in the rat].
In serial semithin sections, by means of a transmission and scanning electron microscopy, perforating holes, through which fluid is transported from the interstitium into the ductal lumens, have been revealed in the deferent duct walls of the palatal salivary glands. The mechanism of how these holes are formed is closely connected with secretory process of glandulocytes and is directly dependent on its intensity. The transmural holes increase porosity of the deferent duct walls, thus they contribute to better moistening of the mouth cavity with fluid both under normal and experimental conditions. Their role is especially important when there is a functional insufficiency of the large salivary glands. There are holes not only in the palatal deferent ducts, but also in other small salivary glands of the mouth cavity.


Magnetic resonance imaging and spectroscopy of regional brain structure in a 10-year-old boy with elevated blood lead levels.
The effects of elevated blood lead levels on the development of children have been examined only in the context of behavioral and neuropsychological evaluations. No studies have examined the effects of lead on brain metabolism in vivo or on structural and/or functional correlates of brain function in children. In the human brain, magnetic resonance spectroscopy (MRS) provides a noninvasive, risk-free method to monitor the biochemistry of acute and chronic stages of disease. The purpose of this study was to examine in vivo the use of MRS for the evaluation of the neurotoxic effects of lead on the nervous system, by detection of brain metabolism, especially N-acetylaspartate, a metabolite shown to decrease in processes that involve neuronal loss. Two male cousins who live in the same household and share the same socioeconomic background and home environment were studied. The subject, a 10-year-old boy, had elevated blood lead levels. His cousin, a 9-year-old boy, was not exposed to lead. Both underwent a comprehensive neuropsychological evaluation and both were evaluated using the magnetic resonance imaging (MRI) and MRS at the University of Pennsylvania Medical Center. High-resolution MRI and MRS were performed using a 3-in surface coil. Localized proton spectra were obtained from contiguous 6 x 6 x 10-mm voxels using one-dimensional phase encoding, with a 2000-millisecond repetition time and a 31-millisecond echo time. Neuropsychological evaluation demonstrated areas of impairment in the lead-exposed child, including difficulties in academic skills of reading, writing, and arithmetic, as well as deficient linguistic skills and attentional mechanism. By contrast, studies of the cousin, who was not exposed to lead, showed overall neuropsychological functioning within normal limits. Although both children had a normal MRI examination of the brain, studies of the lead-exposed boy showed a significant alteration in brain metabolites, with a reduction in the N-acetylaspartate:creatine ratio for both gray and white matter on the MRS examination, compared with his cousin. The present study is a first attempt to determine in vivo metabolic differences in the brain of a child exposed to lead compared with a healthy control subject. This is a unique case because these children were matched on a number of variables usually regarded as confounders in behavioral lead studies, and therefore can be regarded as matched controls. The present study demonstrates that MRS is a feasible, noninvasive technique for in vivo examination of the brains of children exposed to lead. We were able to obtain high-quality spectra from voxels as small as 0.36 cm at 1.5T. The spatial resolution used in the present study is sufficient to obtain spectra from voxels almost exclusively composed of gray matter. The one-dimensional phase-encoding approach used presents the advantage of obtaining several spectra simultaneously in a relatively short time. The present study has allowed us to examine the spectroscopic patterns of frontal gray and white matter after lead exposure relative to the normal pattern seen in healthy children and adults. The MRS study of the healthy, nonlead-exposed cousin demonstrated spectra entirely consistent with the spectral pattern reported in previous studies of healthy individuals. By contrast, the spectra obtained from the lead-exposed child deviated from the expected pattern in all metabolite ratios analyzed. Because N-acetylaspartate has been shown as a measure of neuronal viability, the level of N-acetylaspartate may enable us to evaluate the degree of neuronal loss in children exposed to lead. The MRI examination indicated no structural abnormalities or cortical thinning, and no abnormal findings in either case. By contrast, MRS indicated a significant change from normal values for the lead-exposed child. This supports the idea that lead neurodevelopmental toxicity may be related to inter


SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis.
Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis and progression of liver fibrosis. Identifying core regulators of ECM deposition may lead to urgently needed diagnostic and therapetic strategies for the disease. The transcription factor Sex determining region Y box 9 (SOX9) is actively involved in scar formation and its prevalence in patients with liver fibrosis predicts progression. In this study, transcriptomic approaches of Sox9-abrogated myofibroblasts identified >30% of genes regulated by SOX9 relate to the ECM. Further scrutiny of these data identified a panel of highly expressed ECM proteins, including Osteopontin (OPN), Osteoactivin (GPNMB), Fibronectin (FN1), Osteonectin (SPARC) and Vimentin (VIM) as SOX9 targets amenable to assay in patient serum. In vivo all SOX-regulated targets were increased in human disease and mouse models of fibrosis and decreased following Sox9-loss in mice with parenchymal and biliary fibrosis. In patient serum samples, SOX9-regulated ECM proteins were altered in response to fibrosis severity, whereas comparison with established clinical biomarkers demonstrated superiority for OPN and VIM at detecting early stages of fibrosis. These data support SOX9 in the mechanisms underlying fibrosis and highlight SOX9 and its downstream targets as new measures to stratify patients with liver fibrosis.


Ultraviolet radiation and its effects on pregnancy: A review study.
Seasons and Vitamin D are factors that are directly and indirectly related to ultraviolet (UV) radiations and can affect pregnancy. Therefore, the present study aims at investigating the effects of being exposed to direct UV radiation during pregnancy period and its effects on fetal growth, premature birth, and high blood pressure. This study was conducted by searching different websites such as Medline, Embase, ProQuest, Global Health, Google Scholar, and Scopus. Of the 430 papers found, between 1985 and 2017, seventeen related articles were used. The results showed that being exposed to UV radiation during the first 3 months of pregnancy is associated with improved fetal growth and causes high blood pressure during pregnancy. The literature shows that being women exposure to UV radiation had beneficial effects on fetal growth and blood pressure during pregnancy period. However, since this issue has not been extensively studied in the past, the results from previous studies should be generalized with extreme care and caution. Therefore, it is suggested that further studies be carried out in this area.


Zinc regulation of food intake: new insights on the role of neuropeptide Y.
The role of neuropeptide Y (NPY) in feeding behavior and zinc deficiency-induced anorexia has been controversial because hypothalamic NPY levels are elevated in both zinc deficiency and food restriction. A recent report shows that while NPY is released from terminals in the paraventricular nucleus of the hypothalamus of food-restricted animals, this release is significantly impaired in zinc-deficient animals. Zinc deficiency may therefore cause anorexia by inhibiting the release of NPY that is required for receptor activation.


Formononetin protects against cisplatin‑induced acute kidney injury through activation of the PPARα/Nrf2/HO‑1/NQO1 pathway.
Acute kidney injury (AKI) is characterized by an abrupt deterioration of renal function. Formononetin (FOR) protects against cisplatin (CIS)‑induced AKI, and it has various potential pharmacological and biological effects, including anti‑inflammatory, antioxidative and anti‑apoptotic effects. The current study investigated the role of FOR in CIS‑induced AKI. Rats were treated with CIS to establish an AKI model, followed by treatment with FOR. HK‑2 cells were treated with CIS, FOR, GW6471 [a peroxisome proliferator‑activated receptor α (PPARα) antagonist], eupatilin (a PPARα agonist) and nuclear factor erythroid 2‑related factor 2 (Nrf2) small interfering RNA (siNrf2), and cell proliferation and apoptosis were determined by MTT and flow cytometry assays. The mRNA and proteins levels of PPARα, Nrf2, heme oxygenase‑1 (HO‑1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were measured by reverse transcription‑quantitative PCR and western blotting. The results demonstrated that FOR attenuated the histopathological changes, the levels of blood urea nitrogen, creatinine, TNF‑α and IL‑1β, and the MDA content and MPO activity, whereas it enhanced CAT activity in the AKI rat model. Furthermore, FOR and eupatilin promoted cell viability and CAT activity, and increased the levels of PPARα, Nrf2 and HO‑1 and NQO1, but suppressed apoptosis and MPO activity, and reduced the levels of MDA, TNF‑α and IL‑1β in CIS‑treated HK‑2 cells. Notably, the aforementioned effects were reversed by GW6471 treatment or siNrf2 transfection. In conclusion, FOR protects against CIS‑induced AKI via activation of the PPARα/Nrf2/HO‑1/NQO1 pathway.


[Evolution of the intake and nutritional status of zinc, iron and copper in women undergoing bariatric surgery until the second year after surgery].
Bariatric surgery allows a significant reduction in weight and improvement of comorbidities associated with obesity in the long term, but it can also adversely affect the nutritional status of some micronutrients. To evaluate changes in intake and parameters of nutritional status of zinc, iron and copper in patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG), until the second postoperative year. We prospectively studied 45 women undergoing GBP or SG (mean age 35.2 ± 8.4 years, mean BMI 39.8 ± 4.0 kg/m²), every 6 months We measured intake and status indications nutritional zinc, iron and copper, and annually evaluated body composition. The contribution of minerals through supplements represented twice the recommended intake for a healthy woman in patients undergoing GT and three times for GBP. 20 women underwent GBP and 25 SG. In both groups there was a significant reduction in weight and body fat percentage, which was maintained until the second postoperative year. Women who have had a greater commitment GBP nutritional status of zinc, iron and copper, that patients undergoing SG. Gastric bypass Roux-Y produces a greater commitment of nutritional status of zinc, iron and copper sleeve gastrectomy. It should evaluate whether administration of supplementation fractional improve the absorption of these nutrients.


Autologous stem cell transplantation with busulfan, cyclophosphamide, and etoposide as an intensifying frontline treatment in patients with peripheral T cell lymphomas: a multicenter retrospective trial.
The effectiveness of high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) as a frontline treatment in peripheral T cell lymphomas (PTCLs) is still unclear. We retrospectively investigated the clinical outcomes of HDT/ASCT as an intensifying frontline treatment in 31 patients with newly diagnosed PTCLs. The conditioning regimen of HDT/ASCT consisted of busulfan, cyclophosphamide, and etoposide (BuCyE). At diagnosis, five (16.1 %) patients were classified as high risk according to the prognostic index for PTCL (PIT). The disease status of the patients before HDT/ASCT consisted of 23 patients (74.2 %) with complete response (CR) and eight patients (25.8 %) with partial response (PR). Six (75 %) out of eight patients with PR at pretransplantation were improved in terms of the response to CR after HDT/ASCT. At a median follow-up of 32.4 months, the 3-year probability of overall survival (OS) and progression-free survival (PFS) was 64.5 ± 8.6 %. Transplant-related mortality occurred in three patients (9.7 %), due to septic shock, hemorrhage, and delayed pneumonia, respectively. Bone marrow involvement of PTCL at diagnosis was a poor prognostic factor for OS. In conclusion, frontline HDT/ASCT with a conditioning regimen of BuCyE may be an effective and tolerable intensifying therapeutic option to improve outcomes in patients with PTCLs.


A whole-genome transcriptome analysis of articular chondrocytes in secondary osteoarthritis of the hip.
To date, exhaustive gene expression analyses of chondrocytes in hip osteoarthritis (OA) have yielded specific gene expression patterns. No study has reported on the exhaustive transcriptome of secondary hip OA based on acetabular dysplasia in a Japanese population, while previous reports have focused on primary or idiopathic hip OA in Caucasian populations. This study aims to search for specific gene expression patterns of secondary hip OA chondrocytes by transcriptome analysis. Human articular cartilage was obtained from femoral heads following hemiarthroplasty for femoral neck fracture (N = 8; non-OA) and total hip arthroplasty for secondary hip OA (N = 12). Total RNA was extracted from the articular cartilage and submitted for microarray analysis. The obtained data were used to perform gene expression analysis, GO enrichment analysis and pathway analysis and were compared with data from primary hip OA in Caucasian populations in the literature. We identified 888 upregulated (fold change: FC ≥ 2) and 732 downregulated (FC ≤ 0.5) genes in hip OA versus non-OA chondrocytes, respectively. Only 10% of upregulated genes were common between the secondary and primary OA. The newly found genes prominently overexpressed in the secondary hip OA chondrocytes were DPT, IGFBP7, and KLF2. Pathway analysis revealed extracellular matrix (ECM)-receptor interaction as an OA-related pathway, which was similar to previous reports in primary hip OA. This is the first study to report the genome-wide transcriptome of secondary hip OA chondrocytes and demonstrates new potential OA-related genes. Gene expression patterns were different between secondary and primary hip OA, although the results of pathway and functional analysis were similar.


Von Willebrand factor, ADAMTS13, and thrombotic thrombocytopenic purpura.
Discoveries during the past decade have revolutionized our understanding of idiopathic thrombotic thrombocytopenic purpura (TTP). Most cases in adults are caused by acquired autoantibodies that inhibit ADAMTS13, a metalloprotease that cleaves von Willebrand factor within nascent platelet-rich thrombi to prevent hemolysis, thrombocytopenia, and tissue infarction. Although approximately 80% of patients respond to plasma exchange, which removes autoantibody and replenishes ADAMTS13, one third to one half of survivors develop refractory or relapsing disease. Intensive immunosuppressive therapy with rituximab appears to be effective as salvage therapy, and ongoing clinical trials should determine whether adjuvant rituximab with plasma exchange also is beneficial at first diagnosis. A major unanswered question is whether plasma exchange is effective for the subset of patients with idiopathic TTP who do not have severe ADAMTS13 deficiency.


Prostaglandin E receptors.
Prostaglandin (PG) E(2) exerts its actions by acting on a group of G-protein-coupled receptors (GPCRs). There are four GPCRs responding to PGE(2) designated subtypes EP1, EP2, EP3, and EP4 and multiple splicing isoforms of the subtype EP3. The EP subtypes exhibit differences in signal transduction, tissue localization, and regulation of expression. This molecular and biochemical heterogeneity of PGE receptors leads to PGE(2) being the most versatile prostanoid. Studies on knock-out mice deficient in each EP subtype have defined PGE(2) actions mediated by each subtype and identified the role each EP subtype plays in various physiological and pathophysiological responses. Here we review recent advances in PGE receptor research.


Breath hydrogen and methane: poor indicators of apparent digestion of soy fiber.
To examine whether end-alveolar breath hydrogen and methane could be used as indicators of fiber digestion in humans, 16 male subjects were fed four fiber-free, complete liquid diets with 0, 30 g (heat processed), 30 g, and 60 g/day soy polysaccharide. Breath hydrogen was measured hourly and breath methane every 4 h on days 6 and 8 of each study period. Feces were collected, homogenized, dried, and analyzed for neutral detergent fiber (NDF). NDF in diets was determined and apparent NDF digestibility calculated. NDF from soy was extensively fermented, greater than 80%, on the fiber-containing diets. No significant relationship was found between breath-gas excretion and fiber digestion, although breath-gas values varied greatly. Breath hydrogen and methane were not significantly different when subjects consumed diets containing 0, 30, or 60 g soy polysaccharide.


Inhibition of CXCR4/CXCL12 signaling axis by ursolic acid leads to suppression of metastasis in transgenic adenocarcinoma of mouse prostate model.
Increasing evidences indicate that CXCR4/CXCL12 signaling pathway plays a pivotal role in the process of distant site metastasis that accounts for more than 90% of prostate cancer related deaths in patients. Thus, novel drugs that can downregulate CXCR4/CXCL12 axis have a great potential in the treatment of metastatic prostate cancer. In this report, we tested an agent, ursolic acid (UA) for its ability to modulate CXCR4 expression in prostate cancer cell lines and inhibit metastasis in vivo in transgenic adenocarcinoma of mouse prostate (TRAMP) model. We observed that UA downregulated the expression of CXCR4 in prostate cancer cells irrespective of their HER2 status in a dose- and time-dependent manner. Neither proteasome inhibitor nor lysosomal stabilization had any effect on UA-induced decrease in CXCR4 expression. When investigated for the molecular mechanisms, it was observed that the downregulation of CXCR4 was due to transcriptional regulation as indicated by downregulation of mRNA expression, inhibition of NF-κB activation and modulation of chromatin immunoprecipitation activity. Suppression of CXCR4 expression by UA further correlated with the inhibition of CXCL12-induced migration and invasion in prostate cancer cells. Finally, we also found that UA treatment can inhibit metastasis of prostate cancer to distal organs, including lung and liver and suppress CXCR4 expression levels in the prostate tissues of TRAMP mice. Overall, our experimental findings suggest that UA exerts its antimetastatic effects through the suppression of CXCR4 expression in prostate cancer both in vitro and in vivo.


Effect of vibration on the shear strength of impacted bone graft in revision hip surgery.
We developed a method of applying vibration to the impaction bone grafting process and assessed its effect on the mechanical properties of the impacted graft. Washed morsellised bovine femoral heads were impacted into shear test rings. A range of frequencies of vibration was tested, as measured using an accelerometer housed in a vibration chamber. Each shear test was repeated at four different normal loads to generate stress-strain curves. The Mohr-Coulomb failure envelope from which shear strength and interlocking values are derived was plotted for each test. The experiments were repeated with the addition of blood in order to replicate a saturated environment. Graft impacted with the addition of vibration at all frequencies showed improved shear strength when compared with impaction without vibration, with 60 Hz giving the largest effect. Under saturated conditions the addition of vibration was detrimental to the shear strength of the aggregate. The civil-engineering principles of particulate settlement and interlocking also apply to impaction bone grafting. Although previous studies have shown that vibration may be beneficial in impaction bone grafting on the femoral side, our study suggests that the same is not true in acetabular revision.


Charge-coupled device image sensor as a demodulator in a 2-D polarimeter with a piezoelastic modulator.
It is shown how demodulation of rapidly modulated light beams can be achieved within a single charge-coupled device (CCD). Two interlaced image planes are created by optically masking every second CCD row and transferring the charges back and forth between the two image planes in synchrony with the modulation. The method has been successfully tested for modulation frequencies of 50 and 100 kHz, using integration times up to 1 s. No significant accumulated charge transfer losses are seen for integration times as long as 10(5) modulation cycles (1 s). This demonstrates the feasibility of a CCD polarimeter using piezoelastic modulation of the state of polarization.


Leptomeningeal Relapse of Embryonal Rhabdomyosarcoma after 15 years.
Aim Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumour of childhood. We present the case of a late relapse of RMS to the leptomeninges after 15 years. Methods A 20 year old male presented with a 3 week history of headaches and nausea. He previously had RMS of his right ear diagnosed at age 5 years which was treated with concurrent chemoradiotherapy. An MRI Brain and Spine confirmed extensive leptomeningeal disease and CSF analysis confirmed the presence of recurrent embryonal RMS. Results He completed two cycles of cyclophosphamide and topotecan followed by 45Gy/25Fr of craniospinal radiotherapy. Conclusion Late relapses beyond five years can be seen in up to 9% of patients, however very late recurrences (>10 years) are exceedingly rare. Molecular based methods such as gene expression profiling can aid risk stratification and survivorship clinics may become increasingly useful in following patients with high risk features.


Antioxidant capacity of food mixtures is not correlated with their antiproliferative activity against MCF-7 breast cancer cells.
Combining different foods may produce additive, synergistic, or antagonistic interactions that may modify certain physiological effects (i.e., anticancer properties). For investigating these interactions and potential synergetic combinations, thirteen foods from three categories, including fruits (raspberries, blackberries, apples, grapes), vegetables (broccoli, tomatoes, mushrooms, purple cauliflowers, onions), and legumes (soy beans, adzuki beans, red kidney beans, black beans), were evaluated for their inhibitory activity against MCF-7 breast cancer cells. Grape, onion, and adzuki bean showed maximal growth inhibition of MCF-7 from the fruit, vegetable, and legume groups, respectively. When these three foods were combined in pairs, unique interactions were observed that were not seen when individual extracts were used. Combining onion and grape resulted in a synergistic antiproliferative effect (APE) against MCF-7 compared with either onion or grape treatment alone. In contrast, combining grape and adzuki bean resulted in an antagonistic interaction. Additionally, four antioxidant assays (total phenolic contents, ferric reducing antioxidant power, 2,2-diphenyl-1-picrylhydrazyl, and oxygen radical absorbance capacity) were further used to evaluate the antioxidant capacities (AC) of individual foods and their combinations. Combining raspberry and adzuki bean extracts demonstrated synergistic AC in all four assays, but they did not show synergistic APE against the MCF-7 cells. Combining broccoli and soy produced antioxidant antagonism, but did not have an antagonistic APE against MCF-7. The synergistic or antagonistic AC of food mixtures did not correlate with the synergistic or antagonistic APE against MCF-7. Further investigation is to determine the mechanisms of these interactions and to predict and enhance the therapeutic benefits of foods and food components through strategic food combinations.


Radiographic analysis of the development of periapical lesions in normal rats, sialoadenectomized rats and sialoadenectomized-immunosuppressed rats.
The purpose of this study was to investigate and to compare radiographically the development of periapical lesions in the lower left first molar of normal rats, sialoadenectomised rats and sialoadenectomised-immunosuppressed rats. Sixty male Wistar rats, weighing from 170 to 200 g were utilized. The animals were divided equally into three groups: group I--20 normal rats; group II--20 sialoadenectomised rats; and group III--20 sialoadenectomised-immunosuppressed rats. Groups II and III were sialoadenectomized using the modified Cheyne technique. After 2 weeks, group III was submitted to a immunosuppression regimen by daily subcutaneous cyclosporin A injection (10 mg/kg body weight). After 1 week of immunosuppression for this group, the pulps of all the animals (group I, II and III) were exposed to the oral cavity, to produce apical periodontitis. Five animals of each group were killed 7, 14, 21 and 28 days after pulpal exposure. Their mandibles were surgically removed and radiographically analysed. The lesions were measured using 'Global Lab Image' software. The results showed predictable growth of the lesions during the experimental period. No significant difference was observed between the groups. It was concluded that possible changes in the oral flora and in the host immune response due to xerostomia associated or not to the immunosuppression did not alter the development of the periapical lesions in rats.


Human papillomavirus 16 and head and neck squamous cell carcinoma.
Evidence suggests that human papillomavirus (HPV)16 seropositivity reflects past HPV16 exposure and is associated with risk for head and neck squamous cell carcinoma (HNSCC). Our objectives were to test the hypothesis that HPV16 seropositivity is associated with risk for HNSCC, to correlate HPV16 seropositivity with HPV16 tumor DNA, and to correlate HPV16 seropositivity and HPV16 DNA with sexual history and patient survival. In a case-control study of approximately 1,000 individuals, we assessed serology to the HPV16 L1 protein and in cases only, assayed tumors for HPV16 DNA. HPV16 seropositivity was associated with 1.5- and 6-fold risks for tumors of the oral cavity and pharynx, respectively. There was a dose response trend for HPV16 titer and increasing risk of HNSCC (p < 0.0001) and HPV16 tumor DNA (p < 0.0001). In cases, HPV16 DNA and seropositivity were significantly associated with sexual activity; odds ratios (ORs) of 12.8 and 3.7 were observed for more than 10 oral sexual partners and ORs of 4.5 and 3.2 were associated with a high number of lifetime sexual partners, respectively. Finally, HPV16 seropositivity and HPV16 tumor DNA were associated with hazard ratios of 0.4 and 0.5, respectively, indicating better survival for HPV positive individuals. HPV16 seropositivity was associated with risk for HNSCC, with greatest risk for pharyngeal cancer. We observed dose response relationships between serology titer and both risk for HNSCC and HPV16 tumor DNA. In cases, HPV16 tumor DNA and positive serology were associated with sexual history and improved disease free survival.


Plasma lipoprotein(a) concentration predicts future coronary and cardiovascular events in patients with stable coronary heart disease.
Association between lipoprotein(a) (Lp(a)) level and a first-ever coronary (CHD) event is recognized. Less is evident in patients with overt CHD and stable symptoms in whom we investigated associations between Lp(a) and future events. Relationships between Lp(a) concentration and CHD and cardiovascular disease outcomes during 6 years' median follow-up were evaluated in the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study. Lp(a) concentrations were measured in plasma from 7863 patients who had sustained a previous coronary event and been randomized to pravastatin or placebo. Lp(a) levels were categorized by lowest half, third quartile, 75th to 90th percentile, and highest decile. The prognostic value of Lp(a) on outcomes was assessed by fitting a Cox proportional-hazards model after adjustment for other risk factors and baseline cardiovascular disorders. The prognostic value of a change in Lp(a) at year 1 categorized by quartiles was assessed using Cox regression in a landmark model incorporating the above factors and baseline levels. Baseline Lp(a) concentration was associated with total CHD events (P<0.001), total cardiovascular disease events (P=0.002), and coronary events (P=0.03). Greatest risk occurred at >73 mg/dL, upper decile. For events after year 1, an increase in Lp(a) at 1 year was associated with adverse outcomes for total CHD events and total cardiovascular disease events (P=0.002 each). In the LIPID study, baseline Lp(a) was associated with future cardiovascular disease and CHD events. Increased Lp(a) concentrations after 1 year were also associated with future events, supporting measurement of Lp(a) for risk assessment of patients with known CHD.


Murine orthostatic response during prolonged vertical studies: effect on cerebral blood flow measured by arterial spin-labeled MRI.
High-field MRI scanners are, in principle, well suited for mouse studies; however, many high-field magnets employ a vertical design that may influence the physiological state of the rodent. The purpose of this study was to investigate the orthostatic response of cerebral blood flow (CBF) in mice during a prolonged MR experiment in the vertical position. Arterial spin-labeled (ASL) MRI was performed at 4.7-Tesla with a 15-cm gradient insert that allowed horizontal and vertical CBF measurements to be obtained with the same scanner. For mice in the head-up (HU) vertical position, CBF decreased by approximately 40% compared to the horizontal position, although blood pressure did not differ. Furthermore, CBF values for vertically positioned mice treated with phenylephrine remained constant while blood pressure increased. These results support the conclusion that cerebral autoregulation was intact, albeit at a lower level. Since CBF recovers to near horizontal values by volume loading with saline, it appears that a decrease in central venous pressure (CVP) leading to an increase in sympathetic tone may be a contributing mechanism for lowered CBF. This suggests that using an HU vertical position for MRI in mice may have broader implications, especially for studies that rely on CBF (such as BOLD and fMRI).


Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions.
The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Narrative review. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urokinase-type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the future.


Autosomal recessive Bethlem myopathy.
Bethlem myopathy is a well-defined clinical entity among collagen VI disorders, featuring proximal muscle weakness and contractures of the fingers, wrists, and ankles. It is an early-onset, slowly progressive, and relatively mild disease, invariably associated to date with heterozygous dominant mutations in the 3 collagen VI genes. We have characterized the clinical, laboratory, and genetic features of autosomal recessive Bethlem myopathy in 2 unrelated patients. This study is based on clinical, histochemical, immunocytochemical, and electron microscope evaluation of the muscle and dermal fibroblasts, CT imaging of the muscles, and biochemical and molecular analysis. Both patients carry a truncating COL6A2 mutation (Q819X; R366X) associated with missense changes in the partnering allele lying within the C2 domain of the alpha2(VI) chain (D871N; R843W-R830Q). They show decreased amounts of collagen VI in the basal lamina of muscle fibers and in dermal fibroblast cultures and altered behavior of collagen VI tetramers. Biochemical studies supported the pathogenic effect of identified amino acid substitutions, which involve strictly conserved residues. The reported patients illustrate the occurrence of Bethlem myopathy with a recessive mode of inheritance. This observation completes the hereditary pattern in collagen VI myopathies with both Ullrich congenital muscular dystrophy and Bethlem myopathy underlined by either recessive or dominant effecting mutations. This finding has relevant implications for genetic counseling and molecular characterization of patients with Bethlem myopathy, as well as for genotype-phenotype correlations in collagen VI disorders.


Methods for Gait Analysis During Obstacle Avoidance Task.
In this study, we present algorithms developed for gait analysis, but suitable for many other signal processing tasks. A novel general-purpose algorithm for extremum estimation of quasi-periodic noisy signals is proposed. This algorithm is both flexible and robust, and allows custom adjustments to detect a predetermined wave pattern while being immune to signal noise and variability. A method for signal segmentation was also developed for analyzing kinematic data recorded while performing on obstacle avoidance task. The segmentation allows detecting preparation and recovery phases related to obstacle avoidance. A simple kernel-based clustering method was used for classification of unsupervised data containing features of steps within the walking trial and discriminating abnormal from regular steps. Moreover, a novel algorithm for missing data approximation and adaptive signal filtering is also presented. This algorithm allows restoring faulty data with high accuracy based on the surrounding information. In addition, a predictive machine learning technique is proposed for supervised multiclass labeling with non-standard label structure.


Comparison of Fluoridated Miswak and Toothbrushing with Fluoridated Toothpaste on Plaque Removal and Fluoride Release.
Dental caries and periodontal diseases are all induced by oral biofilm (dental plaque). This study was conducted to evaluate if fluoride-impregnated miswak is as effective in plaque removal and fluoride release as toothbrushing with fluoride toothpaste. This single-blind, randomized, crossover study was conducted at the Department of Cariology, University of Gothenburg, Gothenburg, Sweden, from February 2010 to January 2011. Fifteen healthy subjects participated in this study. The participants were instructed to use the following: (1) 0.5% NaF-impregnated miswak, (2) nonfluoridated miswak, (3) toothbrush with nonfluoride toothpaste, and (4) toothbrush with 1450 ppm fluoride toothpaste. Each method was used twice a day for 1 week after which plaque amount and fluoride concentration in resting saliva were measured. There was a 1-week washout period between each method. No significant difference between miswak and tooth-brushing was found regarding plaque removal on buccal and lingual surfaces. A somewhat higher fluoride concentration in resting saliva was found after using impregnated miswak when compared with toothbrushing with fluoride toothpaste (p < 0.05). Miswak and toothbrushing showed the same plaque removing effect on buccal and lingual surfaces. Miswak impregnated with 0.5% NaF resulted in a higher concentration of fluoride in saliva than brushing with 1450 ppm fluoride toothpaste. Miswak impregnated with 0.5% NaF and toothbrushing results in comparable plaque removal and about the same fluoride concentration in saliva even it was somewhat higher for impregnated miswak.


Clinical studies in the second line setting of advanced pancreatic cancer: are we making any progress?
Despite the enormous advances in clinical research in oncology, the prognosis of pancreatic carcinoma remains poor. The therapeutic options in this type of cancer are very limited, with modest results at present. In the 2012 American Society of Clinical Oncology (ASCO) Annual Meeting, four interesting trials on the second line treatment of pancreatic cancer were presented. The first study (Abstract #4017) with a phase II design suggested that maintenance therapy with sunitinib, after a complete course of standard first line treatment, was feasible and effective while the second phase I/II study (Abstract #4034) evaluated the role of trabedersen, an agent that inhibits TGF-β2 expression. Finally, the efficacy and toxicity of lapatinib combined with either FOLFOX (Abstract #e14533) or capecitabine (Abstract #e14569) were examined in the second line setting of pancreatic cancer.


Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women.
Frailty, as defined by the index derived from the Cardiovascular Health Study (CHS index), predicts risk of adverse outcomes in older adults. Use of this index, however, is impractical in clinical practice. We conducted a prospective cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss, inability to rise from a chair 5 times without using arms, and reduced energy level (Study of Osteoporotic Fractures [SOF index]) with that of the CHS index with the components of unintentional weight loss, poor grip strength, reduced energy level, slow walking speed, and low level of physical activity. Women were classified as robust, of intermediate status, or frail using each index. Falls were reported every 4 months for 1 year. Disability (> or =1 new impairment in performing instrumental activities of daily living) was ascertained at 4(1/2) years, and fractures and deaths were ascertained during 9 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index. Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes. Frail women had a higher age-adjusted risk of recurrent falls (odds ratio, 2.4), disability (odds ratio, 2.2-2.8), nonspine fracture (hazard ratio, 1.4-1.5), hip fracture (hazard ratio, 1.7-1.8), and death (hazard ratio, 2.4-2.7) (P < .001 for all models). The AUC comparisons revealed no differences between models with the CHS index vs the SOF index in discriminating falls (AUC = 0.61 for both models; P = .66), disability (AUC = 0.64; P = .23), nonspine fracture (AUC = 0.55; P = .80), hip fracture (AUC = 0.63; P = .64), or death (AUC = 0.72; P = .10). Results were similar when -2 log likelihood statistics were compared. The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice.


Duty of care and political expectations. Part 3: law and the new code.
Current expectations of nurses, in terms of professional standards, are high. These expectations are dictated from Government manifesto literature from 1997-2001, which reveals the stark political agenda and political promises given to the electorate. Traditionally, the 'standard' expected of a professional was defined according to law - to the precedents set down in common law. Case law reveals that the standards expected of professionals may be different to those expected of nurses, as written in political literature. This article explores the definitions as found in the legal and professional literature. The Nursing and Midwifery Council's Code of Professional Conduct will be reviewed, including the new Code (2008), in order to identify the basis for determining standards expected of, and by, nurses practicing in the clinical arena. The suggestion is that the current level of expectation of professional behaviour of nurses may relate more to the political agenda than the legal definition, and this has resulted in nurse confusion.


Room temperature HFIP/Ag-promoted palladium-catalyzed C-H functionalization of benzothiazole with iodoarenes.
A versatile synthetic protocol involving the room temperature direct arylation of benzothiazole with a wide variety of iodoarenes under Ag-promoted Pd-catalyzed conditions in HFIP as the reaction solvent has been presented. A sequential HFIP-promoted selective iodination of arenes followed by Pd-catalyzed direct arylation of benzothiazole has also been disclosed. The utility of the developed protocol has been demonstrated by the synthesis of anti-tumor agents, PMX-610 and CJM-126 (precursor).


Effectiveness of a pragmatic school-based universal intervention targeting student resilience protective factors in reducing mental health problems in adolescents.
Worldwide, 10-20% of adolescents experience mental health problems. Strategies aimed at strengthening resilience protective factors provide a potential approach for reducing mental health problems in adolescents. This study evaluated the effectiveness of a universal, school-based intervention targeting resilience protective factors in reducing mental health problems in adolescents. A cluster randomised controlled trial was conducted in 20 intervention and 12 control secondary schools located in socio-economically disadvantaged areas of NSW, Australia. Data were collected from 3115 students at baseline (Grade 7, 2011), of whom 2149 provided data at follow up (Grade 10, 2014; enrolments in Grades 7 to 10 typically aged 12-16 years; 50% male; 69.0% retention). There were no significant differences between groups at follow-up for three mental health outcomes: total SDQ, internalising problems, and prosocial behaviour. A small statistically significant difference in favour of the control group was found for externalising problems. Findings highlight the continued difficulties in developing effective, school-based prevention programs for mental health problems in adolescents. ANZCTR (Ref no: ACTRN12611000606987).


Manipulating Light-Matter Interactions in Plasmonic Nanoparticle Lattices.
Rationally assembled nanostructures exhibit distinct physical and chemical properties beyond their individual units. Developments in nanofabrication techniques have enabled the patterning of a wide range of nanomaterial designs over macroscale (>in.2) areas. Periodic metal nanostructures show long-range diffractive interactions when the lattice spacing is close to the wavelength of the incident light. The collective coupling between metal nanoparticles in a lattice introduces sharp and intense plasmonic surface lattice resonances, in contrast to the broad localized resonances from single nanoparticles. Plasmonic nanoparticle lattices exhibit strongly enhanced optical fields within the subwavelength vicinity of the nanoparticle unit cells that are 2 orders of magnitude higher than that of individual units. These intense electromagnetic fields can manipulate nanoscale processes such as photocatalysis, optical spectroscopy, nonlinear optics, and light harvesting. This Account focuses on advances in exciton-plasmon coupling and light-matter interactions with plasmonic nanoparticle lattices. First, we introduce the fundamentals of ultrasharp surface lattice resonances; these resonances arise from the coupling of the localized surface plasmons of a nanoparticle to the diffraction mode from the lattice. Second, we discuss how integrating dye molecules with plasmonic nanoparticle lattices can result in an architecture for nanoscale lasing at room temperature. The lasing emission wavelength can be tuned in real time by adjusting the refractive index environment or varying the lattice spacing. Third, we describe how manipulating either the shape of the unit cell or the lattice geometry can control the lasing emission properties. Low-symmetry plasmonic nanoparticle lattices can show polarization-dependent lasing responses, and multiscale plasmonic superlattices-finite patches of nanoparticles grouped into microscale arrays-can support multiple plasmon resonances for controlled multimodal nanolasing. Fourth, we discuss how the assembly of photoactive emitters on the nanocavity arrays behaves as a hybrid materials system with enhanced exciton-plasmon coupling. Positioning metal-organic framework materials around nanoparticles produces mixed photon modes with strongly enhanced photoluminescence at wavelengths determined by the lattice. Deterministic coupling of quantum emitters in two-dimensional materials to plasmonic lattices leads to preserved single-photon emission and reduced decay lifetimes. Finally, we highlight emerging applications of nanoparticle lattices from compact, fully reconfigurable imaging devices to solid-state emitter structures. Plasmonic nanoparticle lattices are a versatile, scalable platform for tunable flat optics, nontrivial topological photonics, and modified chemical reactivities.


Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) on neurobehavioural development, health and spontaneous behaviour in maternally exposed mice.
Polychlorinated biphenyls (PCBs) are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) in mice, mimicking human exposure during gestation and lactation. Environmentally relevant doses of PCB153 were added to the experimental diets. Feed concentrations were approximately 0.5, 6.5, and 1500 μg PCB153/kg feed, representing a realistic and a worst case scenario of frequent consumption of contaminated fish. The study also investigated the effects of maternal nutrition, i.e. a standard rodent diet versus a high inclusion of salmon. Mice pups were examined for physical- and reflex development, sensorimotor function and spontaneous behaviour from five days after birth until weaning. A selection of pups were followed until 16 weeks of age and tested for open field behaviour and the acoustic startle response (ASR) with prepulse inhibition (PPI). Blood thyroid hormones and liver enzymes, blood lipids and PCB153 content in fat were examined at 16 weeks. Statistical analyses modelled the three way interactions of diet, PCB exposure and litter size on behaviour, using generalized linear models (GLM) and linear mixed effect models (LME). The litter was used as a random variable. Non-parametric tests were used for pair wise comparisons of biochemical analyses. Litter size consistently influenced pup development and behaviour. Few lasting PCB153 related changes were observed, but results indicated effects on synchronization of physical development. Perinatal PCB153 exposure appeared to reduce habituation and cause aggression in males, though not statistically significant. Litter size and maternal diet influenced physical development and function more than PCB153 in perinatally exposed mouse pups and supports the developmental importance of maternal care and the social environment.


Obstetrician-Gynecologists' Strategies to Address Vaccine Refusal Among Pregnant Women.
To describe 1) obstetrician-gynecologists' (ob-gyns') perceptions of the frequency of vaccine refusal among pregnant patients and perceived reasons for refusal and 2) ob-gyns' strategies used when encountering vaccine refusal and perceived effectiveness of those strategies. We conducted an email and mail survey among a nationally representative network of ob-gyns from March 2016 to June 2016. The response rate was 69% (331/477). Health care providers perceived that pregnant women more commonly refused influenza vaccine than tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine: 62% of respondents reported 10% or greater of pregnant women they care for in a typical month refused influenza vaccine compared with 32% reporting this for Tdap vaccine. The most commonly reported reasons for vaccine refusal were patients' belief that influenza vaccine makes them sick (48%), belief they are unlikely to get a vaccine-preventable disease (38%), general worries about vaccines (32%), desire to maintain a natural pregnancy (31%), and concern that their child could develop autism as a result of maternal vaccination (25%). The most commonly reported strategies ob-gyns used to address refusal were stating that it is safe to receive vaccines in pregnancy (96%), explaining that not getting the vaccine puts the fetus or newborn at risk (90%), or that not getting the vaccine puts the pregnant woman's health at risk (84%). The strategy perceived as most effective was stating that not getting vaccinated puts the fetus or newborn at risk. Ob-gyns perceive vaccine refusal among pregnant women as common and refusal of influenza vaccine as more common than refusal of Tdap vaccine. Emphasizing the risk of disease to the fetus or newborn may be an effective strategy to increase vaccine uptake.


Endoplasmic reticulum stress pathway involvement in local and remote myocardial ischemic conditioning.
Remote ischemic perconditioning (RIPer) and local ischemic postconditioning (IPost) are promising methods to decrease ischemia-reperfusion injury. We tested whether these two methods were effective in reducing infarct size through activation of endoplasmic reticulum (ER) stress response, a potential survival pathway. Rats exposed to myocardial ischemia-reperfusion were allocated to one of six groups: control, no intervention at myocardial reperfusion; IPost, three cycles of 10-s coronary artery occlusion followed by 10-s reperfusion applied at the onset of myocardial reperfusion; RIPer, 10-min limb ischemia followed by 10-min reperfusion initiated during coronary artery occlusion; control + 4-PBA, injection of ER stress inhibitor 4-phenylbutyrate (4-PBA) 1 h before coronary occlusion; IPost + 4-PBA; and RIPer + 4-PBA. Infarct size was significantly reduced in IPost and RIPer groups (33.32% ± 3.65% and 21.86% ± 3.98%, respectively) compared with the control group (54.86% ± 6.01%, P < 0.05). Western blot analysis of GRP78 (glucose-regulated protein) level and cleaved activating transcription factor 6, two ER stress markers, demonstrated an enhancement of ER stress response in IPost group but not in RIPer group at 15-min reperfusion. Furthermore, 4-PBA abolished cardioprotection induced by IPost (infarct size 53.75 ± 3.49 vs. 33.32 ± 3.65%, P < 0.05) but not by RIPer (28.80 ± 10.45% vs. 21.86 ± 3.98%, not statistically significant). GRP78 and cleaved activating transcription factor 6 levels were no longer increased in IPost group after 4-PBA. These findings point to a role for ER stress response in cardioprotection against reperfusion injury in IPost but not RIPer, suggesting differences in cardioprotective mechanisms between local and remote conditioning.


Including Arts in Rehabilitation Enhances Outcomes in the Psychomotor, Cognitive, and Affective Domains: A Scoping Review.
The purpose of this scoping review was to analyze the published literature regarding the use of art in the context of rehabilitation for consideration in physical therapy. The CINAHL, PsycArticles, APA PsycInfo, Art Index, Music Index, Cochrane Reviews, and PubMed electronic databases were accessed. Inclusion and exclusion criteria were established and utilized to determine study eligibility. Study details were extracted from each article by researchers using a systematic format. Summation of journal type, participants, dosing and type of intervention, setting and interventionist, outcome domains, and study results were included. Out of 1452 studies, 76 were included for extraction. Of these studies, most had outcome measures aligned with the psychomotor and affective domains of learning (n = 66). Very few studies had outcome measures with psychomotor and cognitive domains (n = 2) or psychomotor, affective, and cognitive outcome measures (n = 8). Regarding the arts used, music, dance, or both were used in 77 instances. Fewer studies reported using creative arts therapy, singing, theater, writing, and rhythm (n = 17). Of the 76 studies analyzed, 74 reported a within-group treatment effect. The arts effectively enhance physical therapist practice; therefore, it is recommended that physical therapists continue to seek collaboration with art professionals and explore the use of arts in practice. Findings demonstrate that combining the arts with physical therapist practice amplifies not only psychomotor but affective and cognitive outcomes as well. The arts have applicability across broad populations (eg, chronic pain, neurologic dysfunction, respiratory conditions). This study supports that physical therapist education and practice should embrace the arts as a collaborative modality to promote enhanced psychomotor, affective, and cognitive outcomes.


Avocatin B Protects Against Lipotoxicity and Improves Insulin Sensitivity in Diet-Induced Obesity.
The effects of an avocado-derived fatty acid oxidation (FAO) inhibitor, avocatin B (AvoB), on glucose and lipid metabolism in models of diet-induced obesity (DIO) and in vitro models of lipotoxicity are evaluated. The safety of its oral consumption in humans is also determined. Mice are given high-fat diets (HFD) for 8 weeks. Thereafter, AvoB or vehicle is administered orally twice weekly for 5 weeks. AvoB inhibits FAO which led to improved glucose tolerance, glucose utilization, and insulin sensitivity. AvoB's effects on metabolism under lipotoxic conditions are evaluated in vitro in pancreatic β-islet cells and C2C12 myotubes. AvoB inhibits FAO and increases glucose oxidation, resulting in lowering of mitochondrial reactive oxygen species that improves insulin responsiveness in C2C12 myotubes and insulin secretion in INS-1 (832/13) cells, respectively. A randomized, double-blind, placebo-controlled clinical trial in healthy human participants is conducted to assess the safety of AvoB consumption (50 mg or 200 mg per day for 60 days). AvoB is well-tolerated and not associated with any dose-limiting toxicity. Therapeutic agents that are safe and effectively inhibit FAO and improve DIO-associated pathologies are currently not available. AvoB's mechanism of action and favorable safety profile highlight its nutritional and clinical importance.


Are prosocials unique in their egalitarianism? The pursuit of equality in outcomes among individualists.
The present research aims to elucidate to what extent the motive to ensure equality in outcomes is general and to what extent it interacts with other important motives such as maximizing own or collective gains. Because individuals may have different considerations and motivations in decision-making situations, it is likely that people with a different social value orientation will respond differently to an unequal distribution of outcomes. Contrary to expectations, not only prosocials care about equality in outcomes. In Study 1, the authors found that individualists choose to forego personal gains, despite obvious selfish reasons to cooperate, when outcomes were distributed unequally. In a second experiment, this finding was replicated and shows that individualists, just as prosocials, demand equality in outcomes in interdependent situations. The studies suggest that typifying individualists as solely being concerned about enhancing personal outcomes is too limited and that fairness norms may trump social value orientation.


Autoimmunity and treatment outcome in melanoma.
Only a subset of melanoma patients with advanced disease seems to benefit from immunotherapy. Predictive markers identifying these patients are unfortunately not available. Whether immune-related side effects could serve as predictors for treatment response or just resemble unwanted side effects from immunotherapy will be outlined in this review. Early studies suggested an association of immune-related side effects such as vitiligo and autoimmune thyroiditis with response in patients receiving IL-2 or IFNα. However, conflicting data have been reported as well, mentioning the effect of a higher rate of immune-related toxicities during prolonged administration of the drug in responders/survivors. This type of bias is also known as guarantee-time bias. Recently, a clearly significant and clinically relevant prolongation of survival was demonstrated in patients with metastatic melanoma treated with ipilimumab. Immune-related adverse events were associated with response to ipilimumab, however, at the cost of considerable toxicity. Evidence for an association of immune-related toxicities and response in patients receiving IL-2 or IFNα is weak, considering guarantee-time bias. On the contrary, this association for patients receiving anti-cytotoxic T-lymphocyte antigen-4 therapy (ipilimumab) appears much stronger. Importantly, can we uncouple tumor immunity from autoimmunity in order to optimize immunotherapy in melanoma?


Kinetic studies on the reaction catalysed by phosphofructokinase from Trypanosoma brucei.
The steady-state kinetics of the reaction catalysed by the bloodstream form of Trypanosoma brucei were studied at pH 6.7. In the presence of 50 mM-potassium phosphate buffer, the apparent co-operativity with respect to fructose 6-phosphate and the non-linear relationship between initial velocity and enzyme concentration, which were found when the enzyme was assayed in 50 mM-imidazole buffer [Cronin & Tipton (1985) Biochem. J. 227, 113-124], are not evident. Studies on the variations of the initial rate with changing concentrations of MgATP and fructose 6-phosphate, the product inhibition by fructose 1,6-bisphosphate and the effects of the alternative substrate ITP were consistent with an ordered reaction pathway, in which MgATP binds to the enzyme before fructose 6-phosphate, and fructose 1,6-bisphosphate is the first product to dissociate from the ternary complex.


Presumed parvovirus B19-associated retinal pigment epitheliopathy.
To describe a patient with a white dot syndrome associated with acute erythema infectiosum. A patient with a clinical history of erythema infectiosum and multifocal punctate white lesions at the level of the retinal pigment epithelium was followed up for an 8-month interval. Serum was tested for immunoglobulin M (IgM) and IgG antibodies to parvovirus B19 at the time of the initial evaluation and during convalescence using an indirect immunofluorescence antibody technique. Serial photographs and fluorescein angiograms were obtained. IgM and IgG antibodies to parvovirus were detected in the serum at the time of initial evaluation; IgM antibodies had disappeared but IgG antibodies persisted in serum obtained at 1-month follow-up. Fundus evaluation revealed clinical disappearance of some lesions, with increased pigmentation of others over the course of follow-up. The authors have identified an adult patient who presented with a white dot syndrome associated with acute erythema infectiosum documented by serologically proved parvovirus B19 infection.


Typologies and Correlates of Police Violence Against Female Sex Workers Who Inject Drugs at the México-United States Border: Limits of De Jure Decriminalization in Advancing Health and Human Rights.
Decriminalization of sex work is increasingly promoted as a structural measure to improve the health of vulnerable groups. In México, sex work is not illegal, but knowledge of policies' street-level impact is limited. This study describes typologies of police violence against female sex workers who inject drugs (FSWID), identifying risk and protective factors for violence exposure to inform policy responses. Survey data were collected during 2008-2010 among HIV-negative FSWID in a behavioral intervention in Tijuana and Ciudad Juarez (N = 584). Latent class analysis identified typologies of police violence in the past 6 months: asked for money, money taken, syringes taken, asked for sex, and sexually assaulted. Structural equation modeling (SEM) predicted latent class membership using sociodemographic, behavioral and risk environment factors, controlling for age, education, marital status, and city. Recent police violence was reported by 68% of FSWID, with three typologies emerging: Low (36.6%); Material (47.8%): having money/syringes taken or being asked for money; and Material/Sexual (15.7%): material violence and being asked for sex or sexually assaulted. In multivariable SEM, Material Violence was associated with: being jailed [adjusted Odds Ratio (aOR) = 4.34], HIV testing (aOR = 2.18), and trading sex indoors (aOR = 1.66). Factors associated with Material/Sexual Violence included: being jailed (aOR = 41.18), injecting with clients (aOR = 3.12), earning more money for sex without a condom (aOR = 2.88), being raped by a client (aOR = 2.13), drinking with clients (aOR = 2.03), receiving substance use treatment (aOR = 1.95), being <18 when first trading sex (aOR = .43), trading sex outdoors (aOR = .53), and poor working conditions (aOR = .56). Despite de jure decriminalization of sex work, police violence against FSWID at the México-United States border is pervasive with implications for sex- and drug-related harms. Closing gaps in policy implementation and mitigating material/sexual violence from police is imperative to decreasing economic vulnerability, risk of overdose and HIV, and improving engagement in HIV and harm reduction services.


Drug usage evaluation of dapsone.
Dapsone has been the principal drug in a multidrug regimen recommended by the World Health Organization for the treatment of leprosy. It is also widely used by dermatologists in varied skin conditions like dermatitis herpetiformis, bullous pemphigoid, Behcet's disease, lupus erythematous and a host of other skin diseases. Hence an attempt has been made to review the utilization and qualitative evaluation of dapsone over a period of 6 months in a tertiary care teaching hospital. The study consisted of 80 patients (54 leprosy and 26 non-leprosy patients), prescribed with dapsone 100 mg oral once daily. The prescribing patterns of dapsone in leprosy and other dermatological conditions (non-leprosy) were analyzed and the safety, efficacy and appropriateness of the doses prescribed were reviewed. The adverse drug reactions observed in the study population were type I Lepra reactions, gastrointestinal side effects (abdominal pain and anorexia), peripheral neuropathy, other nervous side effects (insomnia, headache and vertigo) and other adverse reactions (fever and tinnitus). Patient information leaflets were distributed to patients to educate on the appropriate use of dapsone.


Resource use efficiency of indoor lettuce (Lactuca sativa L.) cultivation as affected by red:blue ratio provided by LED lighting.
LED lighting in indoor farming systems allows to modulate the spectrum to fit plant needs. Red (R) and blue (B) lights are often used, being highly active for photosynthesis. The effect of R and B spectral components on lettuce plant physiology and biochemistry and resource use efficiency were studied. Five red:blue (RB) ratios (0.5-1-2-3-4) supplied by LED and a fluorescent control (RB = 1) were tested in six experiments in controlled conditions (PPFD = 215 μmol m-2 s-1, daylength 16 h). LED lighting increased yield (1.6 folds) and energy use efficiency (2.8 folds) as compared with fluorescent lamps. Adoption of RB = 3 maximised yield (by 2 folds as compared with RB = 0.5), also increasing leaf chlorophyll and flavonoids concentrations and the uptake of nitrogen, phosphorus, potassium and magnesium. As the red portion of the spectrum increased, photosystem II quantum efficiency decreased but transpiration decreased more rapidly, resulting in increased water use efficiency up to RB = 3 (75 g FW L-1 H2O). The transpiration decrease was accompanied by lower stomatal conductance, which was associated to lower stomatal density, despite an increased stomatal size. Both energy and land surface use efficiency were highest at RB ≥ 3. We hereby suggest a RB ratio of 3 for sustainable indoor lettuce cultivation.


Comparison of the humoral response between sheep vaccinated with a killed-virus vaccine and those vaccinated with a modified-live virus vaccine against bluetongue virus serotype 17.
OBJECTIVE To compare the humoral response between sheep vaccinated with a killed-virus (KV) vaccine and those vaccinated with a modified-live virus (MLV) vaccine against bluetongue virus (BTV) serotype 17. DESIGN Randomized clinical trial followed by a field trial. ANIMALS 30 yearling crossbred ewes (phase 1) and 344 sheep from 7 Wyoming farms (phase 2). PROCEDURES In phase 1, ewes seronegative for anti-BTV antibodies received sterile diluent (control group; n = 10) or an MLV (10) or KV (10) vaccine against BTV-17 on day 0. Ewes in the KV group received a second dose of the vaccine on day 21. Ewes were bred 5 months after vaccination and allowed to lamb. Anti-BTV antibodies were measured in ewes at predetermined times after vaccination and in their lambs once at 5 to 10 days after birth. In phase 2, 248 commercial sheep were screened for anti-BTV antibodies and vaccinated with a KV vaccine against BTV-17 on day 0. Sheep seronegative for anti-BTV antibodies on day 0 (n = 90) underwent follow-up serologic testing on day 365 along with 96 unvaccinated cohorts (controls). RESULTS In phase 1, all vaccinated ewes developed anti-BTV antibodies by 14 days after vaccination and remained seropositive for 1 year; all of their lambs were also seropositive. All control ewes and lambs were seronegative. In phase 2, the prevalence of vaccinated sheep with anti-BTV antibodies 1 year after vaccination was 93% and 76% as determined by a serum neutralization assay and competitive ELISA, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Both vaccines induced antibodies against BTV-17 that persisted for at least 1 year and provided passive immunity for lambs and may be a viable option to protect sheep against disease.


Spina bifida cystica. An orthopaedic criterion for the early closure of myelomeningocoeles.
There is an urgent need for criteria upon which to base the decision to close a myelomeningocoele soon after birth. Orthopaedic experience advises that early closure of the spinal lesion should not be done unless there is active flexion power at both hips. This criterion is offered with the knowledge that there may occasionally be other exceptional factors to contradict it, but it is based on experience of 96 personal cases aged between 18 months and 7 years. These cases are analysed and discussed. A further possible criterion for not closing the spinal lesion early is the presence of a gross lumbosacral kyphosis.


The thermal history of human fossils and the likelihood of successful DNA amplification.
Recent success in the amplification of ancient DNA (aDNA) from fossil humans has led to calls for further tests to be carried out on similar material. However, there has been little systematic research on the survival of DNA in the fossil record, even though the environment of the fossil is known to be of paramount importance for the survival of biomolecules over archaeological and geological timescales. A better understanding of aDNA survival would enable research to focus on material with greater chances of successful amplification, thus preventing the unnecessary loss of material and valuable researcher time. We argue that the thermal history of a fossil is a key parameter for the survival of biomolecules. The thermal history of a number of northwest European Neanderthal cave sites is reconstructed here and they are ranked in terms of the relative likelihood of aDNA survival at the sites, under the assumption that DNA depurination is the principal mechanism of degradation. The claims of aDNA amplification from material found at Lake Mungo, Australia, are also considered in the light of the thermal history of this site.


Intestinal Microbiota and Metabolomics Reveal the Role of Auricularia delicate in Regulating Colitis-Associated Colorectal Cancer.
The edible fungus Auricularia delicate (ADe) is commonly employed in traditional medicine for intestinal disorders; however, its inhibitory effect on colitis-associated colorectal cancer (CAC) and the underlying mechanisms remain unexplored. (2) Methods: The inhibitory effect of ADe on CAC was investigated using a mouse model induced by azoxymethane/dextran sulfate sodium. ADe effectively suppressed the growth and number of intestinal tumors in mice. Intestinal microbiota analyses revealed that ADe treatment increased Akkermansia and Parabacteroides while it decreased Clostridium, Turicibacter, Oscillospira, and Desulfovibrio. ADe regulated the levels of 2'-deoxyridine, creatinine, 1-palmitoyl lysophosphatidylcholine, and choline in serum. Furthermore, the levels of these metabolites were associated with the abundance of Oscillospira and Paraacteroides. ADe up-regulated the free fatty acid receptor 2 and β-Arrestin 2, inhibited the nuclear factor kappa B (NF-κB) pathway, and significantly attenuated the levels of inflammatory cytokines, thereby mitigating the inflammatory in CAC mice. The protective effect of ADe in CAC mice is associated with the regulation of intestinal microbiota, which leads to the inhibition of NF-kB pathway and regulation of inflammation.


Impact of hypertension on the lifetime risk of coronary heart disease.
The lifetime risk estimate conveys the probability of disease in the remaining lifetime for an index age. These estimates may be useful for general audience-targeted knowledge translation activities against hypertension. There are only a few reports on the impact of hypertension on the lifetime risk of cardiovascular events. The Suita Study, a cohort study of urban residents, was established in 1989. We included all participants who were coronary heart disease (CHD) free at baseline. Age (in years) was used as the timescale. Age-specific incidence rates were calculated with the person-year method within 5-year bands. We estimated the sex- and index-age-specific lifetime risk of first-ever CHD, taking the competing risk of death into account. We followed 5834 participants from 1989 to 2007 for a total of 75 387.5 person-years. At age 45 years, the competing risk of death-adjusted lifetime risk for all CHD for men was 14.12% for normotensive men and 26.95% for hypertensive men. The competing risk of death-adjusted lifetime risk for all CHD at 45 years of age for women was 6.21% for normotensive women and 14.85% for hypertensive women. This increased lifetime risk of CHD for hypertensive patients was observed among both men and women across all index ages. Although the overall lifetime risk of CHD was lower than in the Western population, hypertension showed a significant effect on the residual lifetime risk of CHD among Japanese middle-aged men and women. This easy-to-understand knowledge may be used as an important index to assist public health education and planning.


The Washington State Nurse Anesthetist Workforce: a case study.
The purposes of this study were to describe the Washington State Certified Registered Nurse Anesthetist (CRNA) workforce and analyze selected dimensions of their clinical practice. We developed the 31-item CRNA Practice Questionnaire. After receiving institutional review board approval, the questionnaire was mailed in 2003 to CRNAs licensed in Washington with an address in Washington, Oregon, and Idaho. Statistical analysis included descriptive statistics for all variables and was performed by University of Washington Center for Health Workforce Studies staff. Results indicate that the typical Washington State CRNA is 50.7 years old, white, and equally likely to be a man or woman. More than half of the Washington State CRNAs are master's educated and have an average of 19 years of CRNA experience. Most work at least 40 hours a week, take call, and earn more than 100,000 dollars per year. Almost all have hospital privileges, but only 30% believe they are equal colleagues with physicians. A chi2 analysis comparing urban and rural respondents yielded few differences except that rural CRNAs reported seeking significantly less consultation and were more likely to take call. Workforce data may assist CRNAs when negotiating with employers and institutions and in resolving interprofessional conflicts and can have implications for scope of practice, policy, and legislative issues.


Multiple neural-network-based adaptive controller using orthonormal activation function neural networks.
A direct adaptive control scheme is developed using orthonormal activation function-based neural networks (OAFNN's) for trajectory tracking control of a class of nonlinear systems. Multiple OAFNN's are employed in these controllers for feedforward compensation of unknown system dynamics. Choice of multiple OAFNN's allows a reduction in overall network size reducing the computational requirements. The network weights are tuned on-line, in real time. The overall stability of the system and the neural networks is guaranteed using Lyapunov analysis. The developed neural controllers are evaluated experimentally and the experimental results are shown to support theoretical analysis. The effects of network parameters on system performance are experimentally evaluated and are presented in this research. The superior learning capability of OAFNN's is demonstrated through experimental results. The OAFNN's were able to model the true nature of the nonlinear system dynamics characteristics for a rolling-sliding contact as well as for stiction.


Salivary Leucocytes as In Vitro Model to Evaluate Nanoparticle-Induced DNA Damage.
Metal oxide nanoparticles (NPs) have a wide variety of applications in many consumer products and biomedical practices. As a result, human exposure to these nanomaterials is highly frequent, becoming an issue of concern to public health. Recently, human salivary leucocytes have been proposed as an adequate non-invasive alternative to peripheral blood leucocytes to evaluate genotoxicity in vitro. The present study focused on proving the suitability of salivary leucocytes as a biomatrix in the comet assay for in vitro nanogenotoxicity studies, by testing some of the metal oxide NPs most frequently present in consumer products, namely, titanium dioxide (TiO2), zinc oxide (ZnO), and cerium dioxide (CeO2) NPs. Primary and oxidative DNA damage were evaluated by alkaline and hOGG1-modified comet assay, respectively. Any possible interference of the NPs with the methodological procedure or the hOGG1 activity was addressed before performing genotoxicity evaluation. Results obtained showed an increase of both primary and oxidative damage after NPs treatments. These data support the use of salivary leucocytes as a proper and sensitive biological sample for in vitro nanogenotoxicity studies, and contribute to increase the knowledge on the impact of metal oxide NPs on human health, reinforcing the need for a specific regulation of the nanomaterials use.


Pareto optimal metabolic engineering for the growth-coupled overproduction of sustainable chemicals.
Our research aims to help industrial biotechnology develop a sustainable economy using green technology based on microorganisms and synthetic biology through two case studies that improve metabolic capacity in yeast models Yarrowia lipolytica (Y. lipolytica) and Saccharomyces cerevisiae (S. cerevisiae). We aim to increase the production capacity of beta-carotene (β-carotene) and succinic acid, which are among the highest market demands due to their versatile use in numerous consumer products. We performed simulations to identify in silico ranking of strains based on multiple objectives: the growth rate of yeast microorganisms, the number of used chromosomes, and the production capability of β-carotene (for Y. lipolytica) and succinate (for S. cerevisiae). Our multiobjective optimization methodology identified notable gene deletions by searching a vast solution space to highlight near-optimal strains on Pareto Fronts, balancing the above-cited three objectives. Moreover, preserving the metabolic constraints and the essential genes, this study produced robust results: seven significant strains of Y. lipolytica and seven strains of S. cerevisiae. We examined gene knockout to study the function of genes and pathways. In fact, by studying the frequently silenced genes, we found that when the GPH1 gene is knocked out in S. cerevisiae, the isocitrate lyase enzyme is activated, which converts the isocitrate into succinate. Our goals are to simplify and facilitate the in vitro processes. Hence, we present strains with the least possible number of knockout genes and solutions in which the genes are turned off on the same chromosome. Therefore, we present results where the constraints mentioned above are met, like the strains where only two genes are switched off and other strains where half of the knockout genes are on the same chromosome. This study offers solutions for developing an efficient in vitro mutagenesis for microorganisms and demonstrates the efficiency of multiobjective optimization in automatizing metabolic engineering processes.


New necessary and sufficient conditions for absolute stability of neural networks.
This paper presents new necessary and sufficient conditions for absolute stability of asymmetric neural networks. The main result is based on a solvable Lie algebra condition, which generalizes existing results for symmetric and normal neural networks. An exponential convergence estimate of the neural networks is also obtained. Further, it is demonstrated how to generate larger sets of weight matrices for absolute stability of the neural networks from known normal weight matrices through simple procedures. The approach is nontrivial in the sense that non-normal matrices can possibly be contained in the resulting weight matrix set. And the results also provide finite checking for robust stability of neural networks in the presence of parameter uncertainties.


Betulinic acid-induced programmed cell death in human melanoma cells involves mitogen-activated protein kinase activation.
Betulinic acid, a naturally occurring triterpene found in the bark of the white birch tree, has been demonstrated to induce programmed cell death with melanoma and certain neuroectodermal tumor cells. We demonstrate currently that treatment of cultured UISO-Mel-1 (human melanoma cells) with betulinic acid leads to the activation of p38 and stress activated protein kinase/c-Jun NH(2)-terminal kinase [widely accepted proapoptotic mitogen-activated protein kinases (MAPKs)] with no change in the phosphorylation of extracellular signal-regulated kinases (antiapoptotic MAPK). Moreover, these results support a link between the MAPKs and reactive oxygen species (ROS). As demonstrated previously, cells treated with betulinic acid generate ROS. Preincubation of cells with antioxidants blocks the process of programmed cell death, and prevents the phosphorylation of p38 and stress activated protein kinase/c-Jun NH(2)-terminal kinase. These data suggest that ROS act upstream of the MAPKs in the signaling pathway of betulinic acid. In addition to mediating these responses, treatment of cells with betulinic acid resulted in a gradual depolarization of mitochondrial membrane potential, a phenomenon established to contribute to the induction of programmed cell death. Interestingly, p38 was capable of partially modulating this perturbation, and investigations of mitochondria-associated apoptotic events indicate no involvement of known caspases. These data provide additional insight in regard to the mechanism by which betulinic acid induces programmed cell death in cultured human melanoma cells, and it likely that similar responses contribute to the antitumor effect mediated with human melanoma carried in athymic mice.


Preparation and Characterization of Blank and Nerolidol-Loaded Chitosan-Alginate Nanoparticles.
Recently, there has been a growing interest in using natural products as treatment alternatives in several diseases. Nerolidol is a natural product which has been shown to have protective effects in several conditions. The low water solubility of nerolidol and many other natural products limits their delivery to the body. In this research, a drug delivery system composed of alginate and chitosan was fabricated and loaded with nerolidol to enhance its water solubility. The chitosan-alginate nanoparticles were fabricated using a new method including the tween 80 pre-gelation, followed by poly-ionic crosslinking between chitosan negative and alginate positive groups. Several characterization techniques were used to validate the fabricated nanoparticles. The molecular interactions between the chitosan, alginate, and nerolidol molecules were confirmed using the Fourier transform infrared spectroscopy. The ultraviolet spectroscopy showed an absorbance peak of the blank nanoparticles at 200 nm and for the pure nerolidol at 280 nm. Using both scanning and transmission electron microscopy, the nanoparticles were found to be spherical in shape with an average size of 12 nm and 35 nm for the blank chitosan-alginate nanoparticles and the nerolidol-loaded chitosan-alginate nanoparticles, respectively. The nanoparticles were also shown to have a loading capacity of 51.7% and an encapsulation efficiency of 87%. A controlled release profile of the loaded drug for up to 28 h using an in vitro model was also observed, which is more efficient than the free form of nerolidol. In conclusion, chitosan-alginate nanoparticles and nerolidol loaded chitosan-alginate nanoparticles were successfully fabricated and characterized to show potential encapsulation and delivery using an in vitro model.


c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation.
The c-Jun NH(2)-terminal kinase (JNK) signaling pathway is induced by cytokines and stress stimuli and is implicated in cell death and differentiation, but the specific function of this pathway depends on the cell type. Here we examined the role of JNK1 and JNK2 in CD8(+) T cells. Unlike CD4(+) T cells, the absence of JNK2 causes increased interleukin (IL)-2 production and proliferation of CD8(+) T cells. In contrast, JNK1-deficient CD8(+) T cells are unable to undergo antigen-stimulated expansion in vitro, even in the presence of exogenous IL-2. The hypoproliferation of these cells is associated with impaired IL-2 receptor alpha chain (CD25) gene and cell surface expression. The reduced level of nuclear activating protein 1 (AP-1) complexes in activated JNK1-deficient CD8(+) T cells can account for the impaired IL-2 receptor alpha chain gene expression. Thus, JNK1 and JNK2 play different roles during CD8(+) T cell activation and these roles differ from those in CD4(+) T cells.


Regional differences in the profile of disabled community-dwelling older adults: A European population-based cross-sectional study.
The main objective of this work was to estimate the prevalence of disability in European community-dwelling older adults, as well as to investigate differences in the profile of disabled older adults between European regions (Northern, Central, Eastern and Southern). A cross-sectional study based on wave 6 (2015) of the Survey of Health, Ageing and Retirement in Europe (SHARE) was conducted. Community-dwelling participants aged 65-84 were selected (n = 33,369). Disability was defined as presenting at least one functional limitation in basic activities of daily living (BADL). Sociodemographic, health services, lifestyle and health-related variables were analyzed. Statistical analysis was carried out through the Chi-square and ANOVA tests for bivariate analysis, and Poisson regression for multivariate analysis. Overall prevalence of disability was 13.8%: 9.4% in the Northern region, 13.1% in the Southern region, 13.6% in the Central region, and 16.6% in the Eastern region. Portugal, Poland, Estonia and Belgium showed the highest prevalence of BADL limitations, while Sweden, Denmark, Greece and Switzerland showed the lowest prevalence. Besides, disabled older adults from East Europe presented the most disadvantaged health profile, followed by the Southern region. On the other hand, disabled older adults living in the Northern region showed the most advantaged characteristics of most variables, except for smoking and polypharmacy.


Enzymatic dehydrogenative polymerization of urushiols in fresh exudates from the lacquer tree, Rhus vernicifera DC.
Fresh exudates from the lacquer tree, Rhus vernicifera DC, were extracted with acetone and the solution was chromatographed to isolate monomer, dimer, trimer, and oligomer fractions of urushiols. Constituents of the monomeric and dimeric fractions were then identified by two-dimensional (2D) 1H-13C heteronuclear multiple quantum coherence (HMQC) and heteronuclear multiple bond coherence (HMBC) NMR spectroscopic techniques. The results showed that the monomeric fraction contained 3-[8'Z,11'E,13'Z-pentadecatrienyl]catechol (1), 3-[8'Z,11'Z,14'-pentadecatrienyl]catechol (2), and 3-pentadecanyl]catechol (3), which was verified by HPLC analysis. The dimeric fraction contained 8'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[9'E,11'E,13'Z-pentadecatrienyl]catechol (4), 14'-(3' ',4' '-dihydroxy-5' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecatrienyl]catechol (5), 2-hydroxyl-3- or -6-alkenylphenyl ethyl ether (6), 14'-(3' ',4' '-dihydroxy-2' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadeca-trienyl]catechol (7), 15'-(2' '-hydroxy-3' '- or -6' '-alkenyl)phenyloxy-3-[8'Z,11'Z,13'E)-pentadecatrienyl]catechol (8), 14'-(2' ',3' '-dihydroxy-4' '-alkenyl)phenyl-3-[8'Z,10'E,12'E-pentadecantrienyl]catechol (9), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,3'-biphenyl (10), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-4,4'-biphenyl (11), 1,1',2,2'-tetrahydroxy-6,6'-dialkenyl-5,4'-biphenyl (12), and 1,2,1'-trihydroxy-6,6'-dialkenyldibenzofuran (13) as constituents. In addition, dimeric ethers and peroxides, such as compounds 14 and 15, were produced by autoxidation of monomeric urushiols in atmospheric air. The possible reaction mechanisms for the dehydrogenative polymerization of urushiols by Rhus laccase present in the fresh raw exudates under the atmospheric oxygen are discussed on the basis of structures identified. This is of primary importance because the use of the urushi exudates as coating materials does not involve organic solvents and is an environmentally friendly process.


Effect of vesicular stomatitis virus matrix protein on host-directed translation in vivo.
Vesicular stomatitis virus infection causes a rapid and potent inhibition of both host transcription and translation. Recently, the viral matrix (M) protein was shown to inhibit host-directed transcription in vivo in the absence of any other viral component (B. L. Black and D. S. Lyles, J. Virol. 66:4058-4064, 1992). The goal of this study was to determine the effect of M protein on host-directed translation. In vitro-transcribed mRNAs encoding M protein and chloramphenicol acetyltransferase (CAT) were cotransfected into BHK cells to determine the effect of M protein expression on translation of CAT mRNA. The results presented here show that M protein did not inhibit host-directed translation of CAT mRNA. On the contrary, this study gave the unexpected result that M protein actually stimulated host-directed translation under the same conditions in which it potently inhibited host-directed transcription. Under these conditions, the combined effect on host gene expression was a greater-than-20-fold inhibition. Furthermore, the enhancement of host translation mediated by M protein was genetically correlated with M protein's ability to inhibit host transcription. Thus, the results of this study establish that M protein does not inhibit host protein synthesis under the same conditions in which it potently inhibits host transcription and suggest that the inhibition of transcription and that of translation by vesicular stomatitis virus require separate viral gene products.


[Advances in the application of prosthetic reconstruction after tumor resection of the distal tibia:a systematic review].
The limited coverage of soft tissue and complex biomechanical factors make resection and reconstruction of distal tibial tumors extremely challenging. Megaprosthesis can provide good mechanical strength for tumor en bloc resection, but there are many postoperative complications, and the problems of insufficient soft tissue coverage and postoperative ankle instability must be solved. The development of three-dimensional digital technology may provide a new treatment strategy for distal tibial reconstruction. Compared to ankle joint preservation endoprostheses, the rapid osseointegration effect of three dimensional-printed megaprosthesis with ankle arthrodesis provides better ankle joint stability and postoperative function. In addition, the three dimensional-printed megaprosthesis may improve complications such as insufficient soft tissue coverage and talus collapse by reducing the circumference of the prosthesis and matching it with the talus through personalized design. Of course, there are few research reports on distal tibial prostheses, and the safety of three dimensional-printed megaprosthesis with ankle arthrodesis needs to be confirmed through extensive long-term follow-up studies. The selection of proximal and distal fixation methods for prostheses needs to be explored in future research.


[Familial heterotaxy syndrome. Case report and review of the international literature].
The authors report two families with two affected siblings of heterotaxy syndrome. Ivemark syndrome with asplenia and complex cardiovascular malformation occurred in two siblings of the first family. The first affected sibling in the second family had situs inversus, transposition of the great arteries with spleen on the right side of the abdomen. Ivemark syndrome with polysplenia and cardiovascular malformation were present in the second affected sibling of the second family. Autosomal recessive inheritance of Ivemark syndrome was reported in the most of the cases, but there are several cases of autosomal dominant inherited Ivemark syndrome. X-linked inheritance of heterotaxy syndrome is also known. Heterotaxy syndromes could also occurred in chromosomal translocation or deletion in sporadic cases. The molecular genetic studies were not able to find the mutation responsible for heterotaxy syndrome. The diagnosis of heterotaxy syndrome could be made by foetal echocardiography until molecular genetic methods are available. Therefore, in the case of positive anamnesis, foetal echocardiography on the 18-20 weeks of gestation is essential diagnostic method.


[The development of methodology, means and device for quick detection of aquatic bacteria in water supply systems of spacecrafts].
Microbial contamination is one of the major characteristics of potable water. The authors give data illustrating occurrence of various microbial species in the inlet products of the water regeneration and supply systems aboard spacecraft. Cultural/biochemical techniques of microbial monitoring (TMM) seem to have the best outlook for potable water assessment in space flight. To qualify water, TMM-I (integral indication of micro-organisms), TMM-C (coccal indication), and TMM-BP (indication of blue pus Pseudomonas aeroginosa) will be necessary and sufficient. Described is a TMM-utilizing unit for microbial analysis.


"Futile Care"-An Emergency Medicine Approach: Ethical and Legal Considerations.
Futility often serves as a proposed reason for withholding or withdrawing medical treatment, even in the face of patient and family requests. Although there is substantial literature describing the meaning and use of futility, little of it is specific to emergency medicine. Furthermore, the literature does not provide a widely accepted definition of futility, and thus is difficult if not impossible to apply. Some argue that even a clear concept of futility would be inappropriate to use. This article will review the origins of and meanings suggested for futility, specific challenges such cases create in the emergency department (ED), and the relevant legal background. It will then propose an approach to cases of perceived futility that is applicable in the ED and does not rely on unilateral decisions to withhold treatment, but rather on avoiding and resolving the conflicts that lead to physicians' believing that patients are asking them to provide "futile" care.