Mechanism of thrombin-induced angiogenesis.
Clinical, laboratory, histopathological and pharmacological evidence support the notion that a systemic activation of blood coagulation is often present in cancer patients. Additionally, thrombin was shown to promote tumour progression and metastasis in animals, and epidemiological studies suggest an increased risk of cancer diagnosis after primary thromboembolism. We have proposed that the aforementioned results may be related to our finding that thrombin is a potent activator of angiogenesis. This is a thrombin receptor-mediated event (the receptor is referred to as protease-activate receptor) and is independent of fibrin formation. Many cellular effects of thrombin on endothelial cells can contribute to the angiogenic action of thrombin. (i) Exposure of endothelial cells to thrombin cause a time- and dose-dependent decrease in the attachment of these cells to basement membrane components, with a concomitant increase in matrix metalloproteinase 2 activation. (ii) Thrombin upregulates the expression of integrin alphavbeta3, the marker of the angiogenic phenotype of endothelial cells. (iii) Thrombin has chemotactic and aptotactic effects on endothelial cells and upregulates the expression of the vascular endothelial growth factor (VEGF) receptors (KDR and Flt1). Thus, thrombin synergizes with the key angiogenic factor VEGF in endothelial cell proliferation. Furthermore, thrombin enhances the secretion of VEGF and matrix metalloproteinase 9 of PC3 prostate cancer cells. These results can explain the angiogenic and tumour-promoting effect of thrombin and provide the basis for development of thrombin receptor mimetics or antagonists for therapeutic application.


Effects of high phosphorus diet on bone metabolism-related gene expression in young and aged mice.
In this study, the effects of high phosphorus (P) diet on bone metabolism-related gene expression were investigated in young and aged mice. Twelve- and 80-week-old ddY male mice were divided into two groups, respectively, and fed a control diet containing 0.3% P or a high P diet containing 1.2% P. After 4 weeks of treatment, serum parathyroid hormone (PTH) concentration was significantly higher in the high P groups than in the control groups in both young and aged mice and was significantly higher in aged mice than in young mice fed the high P diet. High P diet significantly increased receptor activator of NF-κB ligand (RANKL) mRNA in the femur of both young and aged mice and significantly increased the RANKL/osteoprotegerin (OPG) mRNA ratio only in aged mice. High P diet significantly increased mRNA expression of transient receptor potential vanilloid type 6, calbindin-D9k, and plasma membrane Ca(2+)-ATPase 1b in the duodenum of both young and aged mice. These results suggest that high P diet increased RANKL mRNA expression in the femur and calcium absorption-related gene expression in the duodenum regardless of age. Furthermore, the high P diet-induced increase in PTH secretion might increase the RANKL/OPG mRNA ratio in aged mice.


Chewing Entrains Cyclical Actions but Interferes With Discrete Actions in Children.
Functional chewing patterns are achieved early in life prior to other motor skills like walking. Chewing seems to improve specific aspects of attention; however, there is limited research on chewing in dual motor tasks. This study examined relationships between chewing and secondary motor tasks in children. Sixteen typically developing children (13.1 ± 2.3 years) participated in finger tapping, simple reaction time, and walking while chewing at different speeds. The chewing rates varied when produced with a secondary motor task, especially for slow chewing and preferred chewing, and the secondary motor tasks were differentially influenced by the chewing. This relationship was not as strong as what has been reported in adults. It appears the neural oscillatory mechanisms involved in chewing and the secondary motor tasks may not be fully developed in children.


Minimally invasive approach to incarcerated or strangulated groin hernias: A 2018 EAST Master Class Video Presentation.
Groin hernia repair is one of the most common general surgical procedures performed worldwide. Although only a small percentage will become incarcerated or strangulated, this is an indication for repair. Minimally invasive surgery is becoming the standard of care for most procedures, and we believe this to be a safe and feasible approach for incarcerated or strangulated groin hernias. We present a description of our recommended approach with technical details and accompanying video clips to highlight these techniques.


The Checkpoint Kinase 1 Inhibitor Prexasertib Induces Regression of Preclinical Models of Human Neuroblastoma.
Purpose: Checkpoint kinase 1 (CHK1) is a key regulator of the DNA damage response and a mediator of replication stress through modulation of replication fork licensing and activation of S and G2-M cell-cycle checkpoints. We evaluated prexasertib (LY2606368), a small-molecule CHK1 inhibitor currently in clinical testing, in multiple preclinical models of pediatric cancer. Following an initial assessment of prexasertib activity, this study focused on the preclinical models of neuroblastoma.Experimental Design: We evaluated the antiproliferative activity of prexasertib in a panel of cancer cell lines; neuroblastoma cell lines were among the most sensitive. Subsequent Western blot and immunofluorescence analyses measured DNA damage and DNA repair protein activation. Prexasertib was investigated in several cell line-derived xenograft mouse models of neuroblastoma.Results: Within 24 hours, single-agent prexasertib promoted γH2AX-positive double-strand DNA breaks and phosphorylation of DNA damage sensors ATM and DNA-PKcs, leading to neuroblastoma cell death. Knockdown of CHK1 and/or CHK2 by siRNA verified that the double-strand DNA breaks and cell death elicited by prexasertib were due to specific CHK1 inhibition. Neuroblastoma xenografts rapidly regressed following prexasertib administration, independent of starting tumor volume. Decreased Ki67 and increased immunostaining of endothelial and pericyte markers were observed in xenografts after only 6 days of exposure to prexasertib, potentially indicating a swift reduction in tumor volume and/or a direct effect on tumor vasculature.Conclusions: Overall, these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy. Clin Cancer Res; 23(15); 4354-63. ©2017 AACR.


[T-bet gene expression in acute graft versus host disease].
To study the role of T-bet [a T helper 1 (Th1) lymphocyte transcription factor] gene expression in predicting acute graft-versus-host disease (aGVHD) and evaluate the correlation between T-bet gene and aGVHD. Twenty patients who underwent allogeneic stem cell transplantation (allo. HSCT) entered this study. The expression of T-bet gene was examined with reverse transcription (RT)-PCR in bone marrow samples collected from patients on the day before conditioning, and day 0, day 14, day 28, and day 42 after HSCT. The expression level of T-bet in patients developed aGVHD was increased compared with that before conditioning (P = 0.043). The incidence of aGVHD was 91.7% in patients whose T-bet expression level was increased on day 14 after transplant while was 12.5% in those whose T-bet gene expression level was not increased on that day (P < 0.001). Patients with increased expression levels of T-bet after allo-HSCT may have an increased possibility to develop aGVHD. T-bet expression level may serve as an advisable guide to the clinician in predicting aGVHD and monitoring treatment.


Cytosolic tryparedoxin of Leishmania donovani modulates host immune response in visceral leishmaniasis.
Leishmaniasis is a neglected tropical disease caused by the unicellular protozoan parasite of genus Leishmania. Tryparedoxin (TXN) is a low molecular mass dithiol protein belonging to oxidoreductases super-family; which function in concert with tryparedoxin peroxidase (TXNPx) as a system in protozoan parasites including Leishmania. Leishmanial hydroperoxides detoxification cascade uses trypanothione as electron donor to reduce hydroperoxide inside the macrophages during infection. However, the mechanism by which tryparedoxin can contribute in progression of visceral leishmaniasis (VL) and its impact on host's cellular immune response during infection in Indian VL patient is unknown. In this study, we purified a ∼17 kDa recombinant cytosolic tryparedoxin (cTXN) protein of Leishmania donovani (rLdcTXN) and investigated its immunological responses in peripheral blood monocytes (PBMC) isolated from VL patients. The protein significantly enhanced the promastigotes count after 96 h of culture showing a direct correlation with parasite growth. Furthermore, stimulation of PBMC isolated from VL patients with rLdcTXN resulted in up-regulation of IL-4 and IL-10 production whereas IL-12 and IFN-γ was significantly down-regulated suggesting a pivotal role of cTXN in provoking the immune suppression during VL. Our study demonstrates the importance of cTXN protein which can potentially modulate the outcome of disease through suppressing host protective Th1 response in VL patients.


Synthesis of an aggregation-induced emission-based fluorescent probe based on rupestonic acid.
Chinese herbal medicine and Chinese patent medicine have been widely applied for cancer care in China. Rupestonic acid, an active ingredient of Artemisia rupestris L., has recently been confirmed to have certain anti-tumor effects in vitro. In this study, we employed the application of a commonly devoted triphenylamine as a fluorophore and the addition of 2,4-thiazolidinedione as a bridge to integrate rupestonic acid into the AIE system to create an fluorescent probe with anti-tumor properties. The spectral, cytotoxic, and cellular imaging properties of the probe were measured. Its promising responses make possible the application of the probe in antitumor theragnostic systems.


Effect of spinal cord injury on urinary bladder spinal neural pathway: a retrograde transneuronal tracing study with pseudorabies virus.
To determinate the effect of acute and chronic spinal cord injury (SCI) resulting from thoracic cord transection on the urinary bladder spinal neural pathway. Seventy-six adult Sprague-Dawley rats were randomly divided into four groups, non-SCI (normal rats undergoing no surgical procedure except pseudorabies virus [PRV] injection), SCI(b) (SCI and PRV injected immediately after SCI), SCI(c) (SCI and PRV injected at 3 weeks after SCI), and SCI(d) (SCI and PRV injected at 3 months after SCI). Transcardiac perfusion fixation was done at appropriate survival periods after PRV injection into the bladder wall tissue. Sections of the dorsal root ganglion, spinal cord, and brain were processed for visualization of the virus by the streptavidin-peroxidase immunohistochemical procedure. The bladder weight of the non-SCI, SCI(b), SCI(c), SCI(d) rats was 144 +/- 9 mg, 142 +/- 8 mg, 486 +/- 51 mg, and 656 +/- 69 mg, respectively. The time-ordered flow charts of PRV tracing were similar in the non-SCI and SCI rats. The cross-sectional area of the labeled dorsal root ganglion cell profiles increased significantly after SCI (P <0.001): 593 +/- 40 microm2, 588 +/- 39 microm2, 815 +/- 53 microm2, and 902 +/- 57 microm2 in the non-SCI, SCI(b), SCI(c), SCI(d) rats, respectively. The number of labeled cells in the dorsal horn in the L6 and S1 segments 3 days after PRV injection markedly increased in chronic SCI rats, as did the number of labeled motor neurons 4 days after injection. Acute and chronic SCI have no effect on the process of virus transneuronal transport below the level of the lesion. Subsequent to chronic SCI, reorganization of the micturition reflex pathways may occur.


Inherited Thrombocytopenia Caused by Germline ANKRD26 Mutation Should Be Considered in Young Patients With Suspected Myelodysplastic Syndrome.
Thrombocytopenia 2 (THC2) is an autosomal dominant disorder characterized by ankyrin repeat domain 26 mutation and moderate thrombocytopenia. THC2 exposes patients to a low risk of bleeding and an increased likelihood of myelodysplastic syndrome/acute myeloid leukemia. Germline evaluation for a genetic disorder should be considered when a patient presents with isolated thrombocytopenia and associated dysmegakaryopoiesis. In this case report, we present a male patient who presented with isolated thrombocytopenia but was ultimately confirmed to have an inherited THC2 thrombocytopenia/myelodysplastic syndrome. Given the rarity of the disease, no clear guidelines on how to follow THC2 patients over the long term have been established. We recommend a monthly complete blood count and clinical visits every 3 months at a minimum.


Algal Protein Kinase, Triacylglycerol Accumulation Regulator 1, Modulates Cell Viability and Gametogenesis in Carbon/Nitrogen-Imbalanced Conditions.
Nutrient-deprived microalgae accumulate triacylglycerol (TAG) in lipid droplets. A dual-specificity tyrosine phosphorylation-regulated kinase, TAG accumulation regulator 1 (TAR1) has been shown to be required for acetate-dependent TAG accumulation and the degradation of chlorophyll and photosynthesis-related proteins in photomixotrophic nitrogen (N)-deficient conditions (Kajikawa et�al. 2015). However, this previous report only examined particular condition. Here, we report that in photoautotrophic N-deficient conditions, tar1-1 cells, with a mutation in the TAR1 gene, maintained higher levels of cell viability and lower levels of hydrogen peroxide generation and accumulated higher levels of TAG and starch compared with those of wild type (WT) cells with bubbling of air containing 5% carbon dioxide. Transcriptomic analyses suggested that genes involved in the scavenging of reactive oxygen species are not repressed in tar1-1 cells. In contrast, the mating efficiency and mRNA levels of key regulatory genes for gametogenesis, MID, MTD and FUS, were suppressed in tar1-1 cells. Among the TAR1-dependent phosphopeptides deduced by phosphoproteomic analysis, protein kinases and enzymes related to N assimilation and carbon (C) metabolism are of particular interest. Characterization of these putative downstream factors may elucidate the molecular pathway whereby TAR1 mediates cellular propagation and C and N metabolism in C/N-imbalanced stress conditions.


Modeling of Usual Care: Vasopressor Initiation for Sepsis With Hypotension.
Usual care regarding vasopressor initiation is ill-defined. We aimed to develop a quantitative "dynamic practice" model for usual care in the emergency department (ED) regarding the timing of vasopressor initiation in sepsis. In a retrospective study of 589 septic patients with hypotension in an urban tertiary care center ED, we developed a multi-variable model that distinguishes between patients who did and did not subsequently receive sustained (>24 h) vasopressor therapy. Candidate predictors were vital signs, intravenous fluid (IVF) volumes, laboratory measurements, and elapsed time from triage computed at timepoints leading up to the final decision timepoint of either vasopressor initiation or ED hypotension resolution without vasopressors. A model with six independently significant covariates (respiratory rate, Glasgow Coma Scale score, SBP, SpO2, administered IVF, and elapsed time) achieved a C-statistic of 0.78 in a held-out test set at the final decision timepoint, demonstrating the ability to reliably model usual care for vasopressor initiation for hypotensive septic patients. The included variables measured depth of hypotension, extent of disease severity and organ dysfunction. At an operating point of 90% specificity, the model identified a minority of patients (39%) more than an hour before actual vasopressor initiation, during which time a median of 2,250 (IQR 1,200-3,300) mL of IVF was administered. This single-center analysis shows the feasibility of a quantitative, objective tool for describing usual care. Dynamic practice models may help assess when management was atypical; such tools may also be useful for designing and interpreting clinical trials.


Effect of Organic Loading Rate on Anaerobic Digestion Performance of Mesophilic (UASB) Reactor Using Cattle Slaughterhouse Wastewater as Substrate.
In this study, the performance of a laboratory scale upflow anaerobic sludge blanket (UASB) reactor operating at mesophilic temperature (35 °C) was examined. Cattle slaughterhouse wastewater (CSWW) was used as the main substrate. The total and effective volumes of the reactor were 8 L and 6 L, respectively. Twelve different organic loading rates (OLR) were applied and the performance was evaluated. The chemical oxygen demand (COD) removal efficiency was more than 90% during batch study. In the continuous study, COD removal was also approximately 90% at OLR 0.4 g/L d-1 which subsequently dropped to below 50% when the loading rate increased to 15 g/L d-1. Approximately 5 L/d of biogas was obtained with high methane concentration at stages VI and XI corresponding to OLR of 2 and 10 g/L d-1, respectively. It was observed that the concentration of volatile fatty acids was low and that the alkalinity of the wastewater was sufficient to avoid acidification. Specific methane yields of 0.36 and 0.38 LCH₄/g COD added were achieved at OLR 7 and 10 g/L d-1. A hydraulic retention time (HRT) of 1 day was sufficient to remove greater than 70% of COD which correspond to 89% methane concentration. Parameters like soluble COD, NH₃-N, pH, alkalinity, total suspended solid (TSS), fats, oil, and grease were also investigated. The results show that the UASB reactor could serve as a good alternative for anaerobic treatment of CSWW and methane production.


ANNUAL DIFFERENCES IN FEMALE REPRODUCTIVE SUCCESS AFFECT SPATIAL AND COHORT-SPECIFIC GENOTYPIC HETEROGENEITY IN PAINTED TURTLES.
Long-term ecological data were used to evaluate the relative importance of movements, breeding structure, and reproductive ecological factors to the degree of spatial and age-specific variation in genetic characteristics of painted turtles (Chrysemys picta) on the E. S. George Reserve in southeastern Michigan. Estimates of the degree of spatial genetic structuring were based on the proportion of total genotypic variance partitioned within and between subpopulations (inferred from hierarchical F-statistics based on variation at 18 protein loci), and in terms of gene correlations (co-ancestry among individuals derived from reproductive data on full-sib families of females nesting at specific nesting areas). Little variation in allele frequency was observed among turtles from different marshes (Fmt = 0.003), though significant variation was observed among turtles from different nesting areas associated with each marsh (Fnm = 0.046). Gene correlations among individuals within nesting areas varied greatly over years (0.032-0.171; mean = 0.069) and were negatively correlated to the proportion of females that successfully nested during each year. General concordance between independent estimates of genotypic correlations (i.e., Fnm derived from protein electrophoretic variation vs. mean co-ancestry) suggests that allozyme data, when collected over spatial scales consistent with species behavioral characteristics and reproductive ecology, may accurately reflect the apportionment of gene diversity within and among subpopulations. The magnitude and patterning of allelic variation among nesting areas and individuals appears to be primarily a function of gametic correlations among members of full-sib families, irrespective of the degree of gene flow or female nesting-site fidelity. Comparisons of genetic characteristics among 11 cohorts (1974-1984) revealed that heterozygosity (H) and inbreeding coefficients (F) varied greatly. Cohort estimates of H and F were correlated to female nesting success and to estimates of co-ancestry for the same years. Results clearly reflect the concomitant importance of ecological factors (principally the proportion of the female population that successfully produce offspring during each year) in determining the magnitude and patterning of gene correlations within and among groups, and to the genotypic composition of offspring born during each year.


Synthesis, Structure, Reactivity and Catalytic Implications of a Cationic, Acetylide-Bridged Trigold-JohnPhos Species.
The cationic complex [(JohnPhos-Au)3 (acetylide)][SbF6 ] (JohnPhos=(2-biphenyl)di-tert-butylphosphine, L1) has been characterised structurally and features an acetylide-trigold(I)-JohnPhos system; the trinuclear-acetylide unit, coordinated to the monodentate bulk phosphines, adopts an unprecedented μ,η1 ,η2 ,η1 coordination mode with an additional interaction between distal phenyl rings and gold centres. Other cationic σ,π-[(gold(I)L1)2 ] complexes have also been isolated. The reaction of trimethylsilylacetylene with various alcohols (iPrOH, nBuOH, n-HexOH) catalysed by cationic [AuI L1][SbF6 ] complexes in CH2 Cl2 at 50 °C led to the formation of acetaldehyde acetals with a high degree of chemo- and regioselectivity. The reaction mechanism was studied, and several organic and inorganic intermediates have been characterised. A comparative study with the analogous cationic [CuI L1][PF6 ] complex revealed different behaviour; the copper metal is lost from the coordination sphere leading to the formation of cationic vinylphosphonium and copper nanoparticles. Additionally, a new catalytic approach for the formation of this high-value cationic vinylphosphonium has been established.


2'-Benzoyloxycinnamaldehyde-mediated DJ-1 upregulation protects MCF-7 cells from mitochondrial damage.
2'-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent which induces cancer cells apoptosis via reactive oxygen species (ROS) generation. BCA shows more effective antiproliferation in MDA-MB-435 than in MCF-7 breast cancer cells. DJ-1 has been known to protect cells against oxidative stress as an antioxidant because of its cysteine residues sensitive to oxidative stress. In the present study, we evaluated the mechanism of DJ-1 for cell protection from oxidative stress after BCA treatment in MCF-7 cell. BCA upregulates the expression of DJ-1 in MCF-7 cells. However, DJ-1 expression decreased continuously for 24 h after BCA treatment in MDA-MB-435 cells. DJ-1 knockdown sensitized MCF-7 cells to BCA, on the contrary, DJ-1 overexpression induced MDA-MB-435 cells less sensitive to BCA. Confocal microscopic observation showed that only in MCF-7 cells BCA increased the overlapped signal between mitochondria and DJ-1 protein. Mitochondrial membrane potential (MMP) was decreased in MDA-MB-435 cells by BCA, and DJ-1 overexpression inhibited BCA-induced MMP decrease in these cells. On the contrary, DJ-1 knockdown in MCF-7 induced MMP perturbation by BCA. These findings suggest that DJ-1 upregulation protects MCF-7 cells from BCA via inhibiting mitochondrial damage.


A case of recovery from dementia following rejuvenative treatment.
A female patient born in 1931 suffered mental decline for about 1 year. She could no longer conduct her usual activities and home chores and could not hear without a hearing aid. Brain magnetic resonance imaging (MRI) performed in February, 2008, revealed degenerative changes. Treatment consisted of repeated sessions of intermittent hypoxic training (IHT), and individualized vitamins, amino acids, microelements, supplementation, and nutritional adjustment. Until April, 2009, the patient had completed four cycles of IHT and 8 months of the supplementation program. The patient gradually recovered her healthy mental state; she resumed shopping and cooking and began playing piano again, which she was not capable of doing last year. An MRI of her brain performed during April, 2009, showed no degenerative changes.


[Effect of copper intake and copper-zinc ratio on rat lipid peroxidation in copper deficiency].
To study the relations among the copper concentration, the copper-zinc ratio (Cu/Zn) and the biomarkers of lipid peroxidation by controlling the level of copper intake in copper deficiency, to analyze the effect of trace element copper on the rat lipid peroxidation. Determine the content of copper in blood and the activity of superoxide dismutase (SOD), glutathione peroxidase (QSH-Px) and catalase (CAT) and the content of malondialdehyde (MDA), carrying out the relevant research. The rats were treated with copper gluconate (Cu-G) in different doses in the case of insufficient copper intake, the copper concentration in the blood of each group rats presented irregular fluctuate, while the copper-zinc ratio (Cu/Zn) showed a ascending trend following the increase of copper intake, and the results have statistical significance (P < 0.01). In the status of copper deficiency, the SOD activity is lower than the normal level, and then presented a rise trend with the increased of copper intake that is, the ratio of copper-zinc (Cu/Zn). The content of MDA is higher than the normal level, and the content of MDA decreased with the increased of copper intake and the Cu/Zn ratio, and maintained at a relatively low level. The decreased of Cu/Zn ratio could induce the decrease of the CAT activity in the rat blood, while there were no linear correlation be found between them. And no significant effect on the GSH-Px activity in the rat blood in inadequate of copper intake. In copper deficiency, the SOD activity in the rat blood would be lower than the normal level and the content of MDA would increase in rat blood, while with the increase of Cu/Zn ratio, the SOD activity increased gradually, and the content of MDA dropped to a lowed level. While the insufficient intake of copper could induce a increase of the CAT activity in blood and no effect on GSH-Px.


An On-Site Thermoelectric Cooling Device for Cryotherapy and Control of Skin Blood Flow.
Cryotherapy involves the surface application of low temperatures to enhance the healing of soft tissue injuries. Typical devices embody a remote source of chilled water that is pumped through a circulation bladder placed on the treatment site. In contrast, the present device uses thermoelectric refrigeration modules to bring the cooling source directly to the tissue to be treated, thereby achieving significant improvements in control of therapeutic temperature while having a reduced size and weight. A prototype system was applied to test an oscillating cooling and heating protocol for efficacy in regulating skin blood perfusion in the treatment area. Data on 12 human subjects indicate that thermoelectric coolers (TECs) delivered significant and sustainable changes in perfusion for both heating (increase by (±SE) 173.0 ± 66.0%, P < 0.005) and cooling (decrease by (±SE) 57.7 ± 4.2%, P < 0.0005), thus supporting the feasibility of a TEC-based device for cryotherapy with local temperature regulation.


Highly Stable and Regenerative Metal-Organic Framework Designed by Multiwalled Divider Installation Strategy for Detection of Co(II) Ions and Organic Aromatics in Water.
MOF-based sensors capable of effectively and stably detecting toxic species in water have attracted huge attention in terms of improving environmental monitoring levels and water quality. Combining the flexibility of structure and modifying of pore surface, a multiwalled divider installation (MWDI) strategy is proposed and used for property enhancement. We herein report three metal-organic frameworks (MOFs) 1-3 based on a C3 symmetry organic phosphonic ligand with topology increased from 3,6-connected to 3,8-connected. Among them, MOFs 1 and 2 with remaining binding sites and large pores display lower luminescence response to Co2+ than does the applying standard. Guided by the MWDI strategy, 3 with high rigid framework and triple molecular installer divided rhombic pore was achieved under top-down topological analysis as anticipated, which endows high sensitivity and rapid response to Co2+, contributed by the synergy from free activated sites and appropriate pore and molecular dividing effect. Particularly, the high stability of 3 in boiling solvent and acid/base solutions has been evidenced and explained by structural robustness and kinetic inertness. Moreover, 3 shows excellent detection ability toward trinitrophenol (TNP) over other aromatic analytes in water, attributing to the predomination of energy transfers. Of note is that the used framework can be in situ regenerated into a fresh one. That provides a promising strategy to prepare effective and economic luminescent sensors in a predictable way for property modification.


Beware of Osteogenesis Imperfecta: Subdural Hematoma in a 10-Year-Old Child With Minor Head Trauma.
Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by disruption of normal collagen formation resulting in varying degrees of ligamentous laxity and skeletal vulnerability; the low bleeding potential is easily overlooked. Subdural hematoma (SDH) is a common neurosurgical condition, classically related to the rupture of bridging cortico-dural veins after trauma. In the pediatric population, the age distribution shows a massive preponderance for children in their early first decade. We report a very unusual case of SDH in a 10-year-old boy with OI type I, with history of minor trauma. SDH remains exceedingly rare in OI, and its pathophysiology is unclear. To the best of our knowledge, this is the first report of a unilateral subacute SDH associated with OI in a child of such advanced age. These cases may also carry legal ramifications, including misdiagnosis of child abuse in ambiguous situations that are not thoroughly investigated.


Influential factors inducing suboptimal humoral response to vector-based influenza immunisation in Thoroughbred foals.
Numerous equine influenza (EI) epizooties are reported worldwide. EI vaccination is the most efficient methods of prevention. However, not all horses develop protective immunity after immunisation, increasing the risk of infection and transmission. This field study aimed to understand the poor response to primary EI vaccination. The EI antibody response was measured in 174 Thoroughbred foals set in 3 stud farms (SF#1 to SF#3) over a 2years period. All foals were immunised with a commercial recombinant canarypox-based EI vaccine. Sera were tested by single radial haemolysis against the A/equine/Jouars/4/06 EIV strain (H3N8) at the time of the first vaccination (V1), 2weeks and 3months after the second immunisation (V2), 2days and 3months after the third immunisation (V3). The frequency of poor-responders (no detectable antibody titres) was surprisingly elevated after V2 (56.8%), increased to 81.7% at V2+3months and reached 98.6% at V3. The frequency of poor-responder was still 19.2%, 3months after V3. Two independent influential factors were identified. The short (V2+2weeks) and mid-term (V2+3months, V3+3months) antibody levels were positively correlated to the age at V1 (p-value=0.003, 0.031 and 0.0038, respectively). Presence of maternally-derived antibodies (MDA) at V1 was negatively correlated with antibody levels after V3 only (p-value=0.0056). Given that SF#1 antibody response was below clinical protective levels at all-time points studied, the annual boost immunisation (V4) was brought forward by 7.0±1.1months. V1 was delayed by 7weeks the following year, which significantly increased short- and mid-term antibody titres (p-value=9.9e-07 and 2.31e-07, respectively). The age and MDA at first immunisation with the canarypox-based IE vaccine play an independent role in the establishment of antibody levels. This study also highlights the benefit provided by serological surveillance to evaluate herd immunity and to implement corrective management/vaccination measures.


Role for Raf in the entry of viruses associated with AIDS (review).
The biology of acquired immune deficiency (AIDS) is yet to be completely understood partly because it is complicated by the manifestation of various viral infections and associated pathogenesis. Virus entry into target cells is a key step in the virus replication cycle which is characterized by intricate and complex interactions between virus and host cells. Analyses of virus entry are always hampered to some extent due to the inability to mimic in vivo conditions. Emphasis has been placed on understanding what the virus does during the entry process; for example the signaling it mediates during entry, or identifying the cellular receptors with which the virus interact. Often, the role of the cellular environment that is critical for the complex process of virus uptake has taken a back stage. Interestingly, most of the viruses associated with AIDS cause tumors. In a recently concluded study, we identified a role for intracellular oncogenic (Raf) signaling in human herpesvirus-8 (HHV-8/KSHV) infection of target cells. In this review we present an update on entry of various viruses commonly associated with AIDS and yet another novel way of analyzing virus entry.


Essence of care involving nursing students.
In 2001 the Department of Health published The Essence of Care, which aims to improve patient care by identifying and measuring good practice benchmarks. Educators and trainers need to integrate such initiatives into course curricula and develop innovative approaches to enable the contribution of nursing students. This paper describes the initial phase of collaborative work between the University of Southampton's School of Nursing and Midwifery and the local NHS trust which was designed to achieve these aims, including the development of a good practice evaluation tool which students complete at the end of their clinical placements.


Proteome analysis of Phytomonas serpens, a phytoparasite of medical interest.
The protozoan Phytomonas serpens (class Kinetoplastea) is an important phytoparasite that has gained medical importance due to its similarities to Trypanosoma cruzi, the etiological agent of Chagas disease. The present work describes the first proteome analysis of P. serpens. The parasite was separated into cytosolic and high density organelle fractions, which, together with total cell extract, were subjected to LC-MS/MS analyses. Protein identification was conducted using a comprehensive database composed of genome sequences of other related kinetoplastids. A total of 1,540 protein groups were identified among the three sample fractions. Sequences from Phytomonas sp. in the database allowed the highest number of identifications, with T. cruzi and T. brucei the human pathogens providing the greatest contribution to the identifications. Based on the proteomics data obtained, we proposed a central metabolic map of P. serpens, which includes all enzymes of the citric acid cycle. Data also revealed a new range of proteins possibly responsible for immunological cross-reactivity between P. serpens and T. cruzi.


Comparative study of the dentin bond strength of a new universal adhesive.
This study compared the dentin bond strength of a new universal adhesive with that of contemporary multi-step dentin adhesives. Six experimental groups were prepared according to the adhesives used and their application modes: Optibond FL (OB), Adper Single Bond Plus (SB), One-Step Plus (OS), Clearfil SE Bond (CS), All-Bond Universal using etch-and-rinse mode (ABE), and AllBond Universal using self-etch mode (ABS). Micro-tensile bond strength (µTBS) and failure mode were evaluated for each group. The bonded interface was analyzed using transmission electron microscopy (TEM). As a result, µTBS of 6 experimental groups was followed as: OB=ABE=SE=ABS>SB>OS group. TEM micrographs of ABE and ABS groups revealed a homogenous adhesive layer formation. In conclusion, a new universal adhesive can make reliable bond to dentin, regardless of the application mode.


Clinical evaluation of the Ortho Rubella ELISA Test System.
The Ortho Rubella ELISA Test System (Ortho Diagnostics Canada Ltd., Toronto, Ontario) is an enzyme-linked immunosorbent assay (ELISA) for the determination of IgG antibodies to rubella virus. Comparison of the Ortho Rubella ELISA with a commercial hemagglutination inhibition (HAI) test revealed that the ELISA is well suited for routine use as a qualitative screening test for rubella immune status or the demonstration of seroconversions. Quantitation of rubella antibodies by the Ortho Rubella ELISA, however, requires that ELISA endpoint determination be made on serial serum dilutions.


N-Acylethanolamines: lipid metabolites with functions in plant growth and development.
Twenty years ago, N-acylethanolamines (NAEs) were considered by many lipid chemists to be biological 'artifacts' of tissue damage, and were, at best, thought to be minor lipohilic constituents of various organisms. However, that changed dramatically in 1993, when anandamide, an NAE of arachidonic acid (N-arachidonylethanolamine), was shown to bind to the human cannabinoid receptor (CB1) and activate intracellular signal cascades in mammalian neurons. Now NAEs of various types have been identified in diverse multicellular organisms, in which they display profound biological effects. Although targets of NAEs are still being uncovered, and probably vary among eukaryotic species, there appears to be remarkable conservation of the machinery that metabolizes these bioactive fatty acid conjugates of ethanolamine. This review focuses on the metabolism and functions of NAEs in higher plants, with specific reference to the formation, hydrolysis and oxidation of these potent lipid mediators. The discussion centers mostly on early seedling growth and development, for which NAE metabolism has received the most attention, but also considers other areas of plant development in which NAE metabolism has been implicated. Where appropriate, we indicate cross-kingdom conservation in NAE metabolic pathways and metabolites, and suggest areas where opportunities for further investigation appear most pressing.


Cobalt-Catalyzed Regio- and Stereoselective Hydrosilylation of 1,3-Diynes To Access Silyl-Functionalized 1,3-Enynes.
A regio- and stereoselective hydrosilylation of 1,3-diynes has been developed relying on catalysts generated from bench-stable Co(acac)2 and dppp ligand. A variety of symmetrical and unsymmetrical 1,3-diynes undergo this transformation, yielding the corresponding silyl-functionalized 1,3-enynes in high yields with excellent regioselectivity. Gram-scale reactions and further transformations of the silyl-containing 1,3-enyne products highlight the synthetic utilities of this Co-catalyzed hydrosilylation of 1,3-diynes.


Inelastic electron transport in polymer nanofibers.
In this paper we present theoretical analysis of the electron transport in conducting polymers being in a metal-like state. We concentrate on the study of the effects of temperature on characteristics of the transport. We treat a conducting polymer in the metal state as a network of metalliclike grains embedded in poorly conducting environment, which consists of randomly distributed polymeric chains. We carry out the present studies assuming that the intergrain conduction is mostly provided by electron quantum tunneling via intermediate states localized on polymer chains between the grains. To analyze the effects of temperature on this kind of electron intergrain transport we represent the thermal environment as a phonon bath coupled to the intermediate state. The electron transmission is computed using the Buttiker model within the scattering matrix formalism. This approach is further developed, and the dephasing parameter is expressed in terms of relevant energies including the thermal energy. It is shown that temperature dependencies of both current and conductance associated with the above transport mechanism differ from those typical for other conduction mechanisms in conducting polymers. This could be useful to separate out the contribution from the intergrain electron tunneling to the net electric current in transport experiments on various polymer nanofibers. The proposed model could be used to analyze inelastic electron transport through molecular junctions.


The psychometric properties of Turkish version of the Modified Paediatric Mini Mental Scale.
Children with neurological diseases suffer from neurocognitive problems due to both the disease and the treatment processes. Therefore, it is necessary that a battery can be used to determine and track the cognitive function of these children. The aim of this study is to establish the Turkish version of the Modified Paediatric Mini Mental Scale (MPMMS), ensure its cultural adaptation, and test the validity and reliability of the Turkish version of the MPMMS. Sixty-five children with the neurological condition were enrolled in this methodological study. The subjects' age, height, weight, and body mass index were recorded. The MPMMS and the social function subscale of the Paediatric Evaluation of Disability Inventory (PEDI) were used to assess the participants' cognitive function. The construct validity of the questionnaire was determined by the correlation between the MPMMS and the social function subscale of the PEDI. Cronbach's alpha was calculated to determine internal consistency. To determine test-retest reliability, 32 children were assessed 7-14 days after the initial assessment, and the intraclass correlation coefficient (ICC) was calculated. The mean age of the participants was 9.26 ± 3.87 years. A very strong significant correlation was found between the MPMMS and social function subscale of the PEDI (r = 0.935, p = 0.000). The internal consistency of the MPMMS was excellent (Cronbach's alpha = 0.932). The Turkish version of the MPMMS has excellent validity and reliability and can be used by professionals in various health care settings to determine children's cognitive abilities.


Identification of key candidate genes and pathways in glioblastoma by integrated bioinformatical analysis.
Glioblastoma (GBM), characterized by high morbidity and mortality, is one of the most common lethal diseases worldwide. To identify the molecular mechanisms that contribute to the development of GBM, three cohort profile datasets (GSE50161, GSE90598 and GSE104291) were integrated and thoroughly analyzed; these datasets included 57 GBM cases and 22 cases of normal brain tissue. The current study identified differentially expressed genes (DEGs), and analyzed potential candidate genes and pathways. Additionally, a DEGs-associated protein-protein interaction (PPI) network was established for further investigation. Then, the hub genes associated with prognosis were identified using a Kaplan-Meier analysis based on The Cancer Genome Atlas database. Firstly, the current study identified 378 consistent DEGs (240 upregulated and 138 downregulated). Secondly, a cluster analysis of the DEGs was performed based on functions of the DEGs and signaling pathways were analyzed using the enrichment analysis tool on DAVID. Thirdly, 245 DEGs were identified using PPI network analysis. Among them, two co-expression modules comprising of 30 and 27 genes, respectively, and 35 hub genes were identified using Cytoscape MCODE. Finally, Kaplan-Meier analysis of the hub genes revealed that the increased expression of calcium-binding protein 1 (CABP1) was negatively associated with relapse-free survival. To summarize, all enriched Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways may participate in mechanisms underlying GBM occurrence and progression, however further studies are required. CABP1 may be a key gene associated with the biological process of GBM development and may be involved in a crucial mechanism of GBM progression.


The Effect of α-lipoic Acid on C-Reactive Protein Level: A Meta-analysis of Randomized, Double-Blind, and Placebo-Controlled Studies.
The C-reactive protein is generally considered a marker of inflammation, and it is widely used in clinical practice as a minimally invasive index of any ongoing inflammatory response. Alpha-lipoic acid (ALA) supplementation can be beneficial for human health, especially in the sense of its anti-inflammatory action. The aim of this meta-analysis was to, based on the currently available highest level of evidence (prospective, randomized, double-blind, and placebo-controlled data), investigate the effect of ALA supplementation on CRP levels. Prospective, randomized, double-blind, and placebo-controlled clinical trials were extracted after a systematic search of PubMed, the Cochrane Library, the Web of Science, EMBASE, and the Scopus databases. A random effect model was used in this meta-analysis to investigate the influence of ALA on the blood CRP level. The subgroup analysis and meta-regression were used to identify the source of heterogeneity. This meta-analysis provided evidence of the positive effect of ALA on the reduction of the blood CRP level. The subgroup analysis and meta-regression results indicated that ALA can reduce the CRP level when administrated at a 600 mg dose, and not in higher or lower doses. Also, a shorter duration of study positively correlates with the reduction of CRP after ALA supplementation.


Application of network methods for understanding mental disorders: pitfalls and promise.
Galvanized with the availability of sophisticated statistical techniques and large datasets, network medicine has emerged as an active area of investigation. Following this trend, network methods have been utilized to understand the interplay between symptoms of mental disorders. This realistic approach that may provide an improved framework into understanding mental conditions and underlying mechanisms is certainly to be welcomed. However, we have noticed that symptom network studies tend to lose sight of the fundamentals, overlook major limitations embedded in study designs, and make inferences that are difficult to justify with current findings. There is concern that disregarding these flaws may halt the progress of the network approach in psychiatry. Therefore, in this paper, we first attempt to identify the pitfalls: (1) a reductionist understanding of medicine and psychiatry, thereby inadvertently reintroducing the dichotomy of medicine (lung cancer) and psychiatry (depression), (2) a shortsighted view of signs and symptoms, (3) overlooking the limitations of available datasets based on scales with embedded latent class structures, (4) overestimating the importance of the current findings beyond what is supported by the study design. By addressing current issues, the hope is to navigate this rapidly growing field to a more methodologically sound and reproducible path that will contribute to our understanding of mental disorders and its underlying mechanisms.


An unusual presentation of seborrheic keratoses in a man with hereditary hemochromatosis.
Hereditary hemochromatosis is an autosomal recessive disorder that disturbs iron metabolism and results in iron deposition throughout the body. Iron accumulation in various organs may cause a wide range of systemic symptoms and cutaneous manifestations of the disease are particularly striking. Classically, hereditary hemochromatosis has been termed "bronze diabetes." Although diffuse hyperpigmentation is a well-described feature of this disease, other cutaneous symptoms may also occur, and a variety of anomalies may be observed. We present a case of long-standing hereditary hemochromatosis associated with hypopigmented plaques, which were found to be seborrheic keratoses on histologic examination. The cutaneous findings in hereditary hemochromatosis are summarized and an unusual case of seborrheic keratosis manifesting as hypopigmented plaques in a man with hereditary hemochromatosis is described. PubMed was used to search the following terms: hemochromatosis, hereditary, hyperpigmentation, hypopigmentation, keratosis, melanin, seborrheic, siderosis. Despite the generalized hyperpigmentation that is usually observed in hereditary hemochromatosis, seborrheic keratosis may present rarely as hypopigmented lesions in individuals affected by this disease. Therefore, seborrheic keratoses should be considered in the differential diagnosis in hemochromatosis patients who present with uncharacteristic pigmentation.


Dapagliflozin for the treatment of type 1 diabetes mellitus.
In 2017, the management of type 1 diabetes mellitus (T1DM) remains intriguing for the clinician, who has to balance between adequate glycemic control and untoward events related to insulin up-titration. Thus, agents that will complement insulin actions and reduce adverse effects are highly welcome. Areas covered: In this review, the authors summarize results from studies on the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin in T1DM. Expert opinion: In T1DM, dapagliflozin is associated with significant antihyperglycemic and metabolic properties, which are achieved with reduction or stabilization of insulin dose and with a very low trend for hypoglycemia. However, there is a lot to learn with respect to diabetic ketoacidosis (DKA), bone fractures and lower limb ischemia.


Transverse mode switchable fiber laser through wavelength tuning.
We report a fiber laser design that is capable of producing switchable transverse modes through wavelength tuning. The transverse mode switching is realized by exploiting the particular transverse mode-wavelength association characteristics of the few-mode fiber Bragg grating. Different transverse mode outputs with high spatial mode quality can be obtained by adjusting the oscillating wavelength with a tunable filter within the fiber laser cavity. For each of the spatial mode outputs, the laser operates at the corresponding single wavelength with narrow linewidth. Through adding polarization controllers in the laser cavity, output modes with cylindrical vector polarization are also realized.


Modified chemotactic peptides: synthesis, conformation, and biological activity of For-Thp-Leu-delta ZPhe-OMe.
For-Thp-Leu-delta ZPhe-OMe (2), an analogue of the chemotactic tripeptide For-Met-Leu-Phe-OMe, containing 4-aminotetrahydrothiopyran-4-carboxylic acid (Thp) and (Z)-2,3-didehydrophenylalanine (delta ZPhe) as achiral, conformationally restricted mimics of Met and Phe, respectively, has been synthesized. In the crystal the new formyltripeptide adopts a type I beta-turn conformation stabilized by a weak H bond between the formylic oxygen and the delta ZPhe NH. 1H-nmr analysis based on NH solvent accessibility and nuclear Overhauser effect experiments suggests that the beta-turn is not preferred in CDCl3 solution where a gamma-turn, centered at the Thp residue, prevails. The biological activity of 2 has been determined on human neutrophils and compared to that of previously studied analogues. The tripeptide 2 is practically unable to elicit superoxide anion production and lysozyme release, while slight, but not statistically significant activity was induced in chemotaxis. The role of the orientation of the aromatic ring with respect to the backbone adjacent atoms is discussed.


Generalizing the Concept of Specific Compound Formulation Additives towards Non-Fluorescent Drugs: A Solubilization Study on Potential Anti-Alzheimer-Active Small-Molecule Compounds.
Tailor-made compound formulation additives enable the testing of potential drugs with undesirable pharmacological profiles. A combinatorial approach using Raman microscopy as the readout method is presented to select peptide sequences from large one-bead-one-compound libraries. The resulting peptide-PEG conjugates solubilize potential prophylactic and therapeutic anti-Alzheimer compounds and can be used as specific additives not only for fluorescent but also for non-fluorescent compounds.


Hyperspectral imaging in quality control of inkjet printed personalised dosage forms.
The aim of the study was to investigate applicability of near infra-red (NIR) hyperspectral imaging technique in quality control of printed personalised dosage forms. Inkjet printing technology was utilized to fabricate escalating doses of an active pharmaceutical ingredient (API). A solution containing anhydrous theophylline as the model drug was developed as a printable formulation. Single units solid dosage forms (SDFs) were prepared by jetting the solution onto 1 cm × 1 cm areas on carrier substrate with multiple printing passes. It was found that the number of printing passes was in excellent correlation (R(2)=0.9994) with the amount of the dispensed drug (μg cm(-2)) based on the UV calibration plot. The API dose escalation was approximately 7.5 μg cm(-2) for each printing pass concluding that inkjet printing technology can optimally provide solutions to accurate deposition of active substances with a potential for personalized dosing. Principal component analysis (PCA) was carried out in order to visualize the trends in the hyperspectral data. Subsequently, a quantitative partial least squares (PLS) regression model was created. NIR hyperspectral imaging proved (R(2)=0.9767) to be a reliable, rapid and non-destructive method to optimize quality control of these planar printed dosage forms.


Epidermal growth factor receptor and KRAS mutations in Brazilian lung cancer patients.
Epidermal growth factor receptor is involved in the pathogenesis of non-small cell lung cancer and has recently emerged as an important target for molecular therapeutics. The KRAS oncogene also plays an important role in the development of lung cancer. The aim of this study was to evaluate the frequency of epidermal growth factor receptor and KRAS mutations in a population of Brazilian patients with non-small cell lung cancer. A total of 207 specimens from Brazilian patients with non-small cell lung cancer were analyzed for activating epidermal growth factor receptor and KRAS somatic mutations, and their associations with clinicopathological characteristics (including age, gender, ethnicity, smoking habits, and histological subtype) were examined. We identified 63 cases (30.4%) with epidermal growth factor receptor mutations and 30 cases (14.6%) with KRAS mutations. The most frequent epidermal growth factor receptor mutation we detected was a deletion in exon 19 (60.3%, 38 patients), followed by an L858R amino acid substitution in exon 21 (27%, 17 patients). The most common types of KRAS mutations were found in codon 12. There were no significant differences in epidermal growth factor receptor or KRAS mutations by gender or primary versus metastatic lung cancer. There was a higher prevalence of KRAS mutations in the non-Asian patients. Epidermal growth factor receptor mutations were more prevalent in adenocarcinomas than in non-adenocarcinoma histological types. Being a non-smoker was significantly associated with the prevalence of epidermal growth factor receptor mutations, but the prevalence of KRAS mutations was significantly associated with smoking. This study is the first to examine the prevalence of epidermal growth factor receptor and KRAS mutations in a Brazilian population sample with non-small cell lung cancer.


Intraoperative awakening of the patient during orthognathic surgery: a method to prevent the condylar sag.
The intraoperative diagnosis, during orthognathic procedures, of an unfavorable condylar position is highly desirable. A simple technique that can reliably identify a malpositioned condyle intraoperatively has obvious advantages. The manual positioning of the condyle is easier, but it requires the utmost care and an experienced operator. Muscle tone is described as maintaining contact across the temporomandibular joint. The anesthetized and curarized patient has a condylar position posterior to that in the same patient when he is awake, with the same seating force applied. Under general anesthesia, the condyle may be inferior and might not feel stable until it moves posteriorly and has adequate compression of the retrodiscal tissues on the posterior wall. Relapse of the occlusion as a result of changes in the condylar position may occur immediately after the removal of the temporary intermaxillary fixation (IMF). The surgeon needs to understand the mechanism of condylar sag and the specific patterns of malocclusion that it may produce. This will enable him to make a diagnosis and to implement the appropriate corrective measures, providing the opportunity for immediate correction of condylar position, thereby obviating the need for a second operation or orthodontic compromise. A study group (group A, 76 patients) and a control group (group B, 73 patients) were randomly formed from the dysgnathic patients scheduled for bimaxillary orthognathic surgery (Le Fort I osteotomy and bilateral sagittal split osteotomy). The free mandibular proximal segment was gently and manually positioned in the glenoid fossa. All the mandibles were fixed with bicortical screws. In group A, immediately after the fixation, IMFs were removed and the occlusions were checked with light digital pressure on the chin, then the patients were rapidly awakened (maintaining the intubation) in a state of conscious analgo-sedation and asked to open and close, and to laterally move the mandible. If clinical examination of the passive and active movements of the mandible was suitable, the anesthesia was reinforced and the operation was concluded. In 11 of the 76 patients of group A, malocclusion was noted, after the rigid fixation, with the method of digital pressure on the chin; the intraoperative awakening of the patients confirmed the clinical appearance and it provided further clinical signs to identify the offending condyle and to favor appropriate corrections. In 8 of the group A patients, malocclusions were not noted with manipulation of the mandible, but they were pointed out during the intraoperative awakening, and then they were appropriately corrected. In 2 of the group B patients, malocclusion was noted, after the rigid fixation, with the method of digital pressure on the chin, and it was immediately corrected. In 7 of the group B patients, malocclusion was not noted during the operation with the method of digital pressure on the chin, but it was noted at the end of the surgical procedure (12-24 hours after). Muscle tone, muscular activity, and proprioception appear to have important roles in the clinical evidence of a postoperative malocclusion during the intraoperative awakening; they can reliably implement the accuracy of the diagnosis of condylar sag, and they can favor its correction.


15-PGDH inhibitors: the antiulcer effects of carbenoxolone, pioglitazone and verapamil in indomethacin induced peptic ulcer rats.
15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the enzyme responsible for prostaglandins (PGs) metabolism. PGs have an important role in the protection of stomach mucosa against destructive stimuli. The aim of the present study is to investigate the inhibitory effect of carbenoxolone, pioglitazone and verapamil on 15-PGDH enzyme. The experiments were carried out in the Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt from May 2011 to August 2011. Adult male albino rats were fasted for 18 hours before administration of high dose of indomethacin (30 mg/kg, p.o.), except for the negative control group which received saline only, followed by pyloric ligation to induce acute gastric ulcers. The rats were pretreated orally with saline, pioglitazone (20 mg/kg), verapamil (25 mg/kg), carbenoxolone (30 mg/kg) or their combinations 30 minutes before indomethacin. The rats were sacrificed after four hours of pyloric ligation. The effects of the previous treatments on the ulcer index (Ui), the microscopic appearance of gastric mucosa, the gastric acid output, the gastric barrier mucus content, and 15-PGDH enzyme activity were determined. Indomethacin resulted in severe ulceration and increased gastric acid output (p < 0.05) compared to negative control. The rats pretreated with carbenoxolone, pioglitazone, verapamil had reduced ulcer index, gastric acid output and 15-PGDH activity (p < 0.05) compared to either indomethacin group or the negative control group. Individual treatments with carbenoxolone, pioglitazone or verapamil increased gastric barrier mucus (p < 0.05) compared to either indomethacin group or the negative control group. The combinations of verapamil with either carbenoxolone or pioglitazone caused further reduction in ulcer index, gastric acid output and 15-PGDH activity (p < 0.05), while causing further increase in gastric barrier mucus (p < 0.05) compared to their respective individual treatment group. The antiulcer properties of pioglitazone and verapamil are, in part, consequences of their inhibitory effect on the enzyme 15-PGDH, responsible for PGs degradation, and the resultant prolongation of PGE2 biological activity in rat stomach mucosa.


Influence of gravity changes induced by parabolic flight on cytokine production in mouse spleen.
Dysregulation of the immune system has been a well-documented effect of human exposure to a microgravity environment during space flight. These effects have included altered cytokine production, reduced proliferative responses, altered signal transduction pathways and altered distribution of peripheral immune cells. Recent reports have documented immunologic studies performed in-flight. When tested during space flight, delayed-type hypersensitivity was reduced, indicating a dysregulation of cell-mediated immune function. However, the mechanisms by which this occurs remain unclear. The production of cytokines plays a critical role in the ability of a host to mount an immune response against an invading microorganism. In this study, the alteration of cytokine responses in mice following parabolic flight (PF) was investigated.


Therapeutic Drug Monitoring of Levetiracetam in Select Populations.
Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) that has a more favorable side effect profile compared to older AEDs. Therapeutic drug monitoring (TDM) of LEV is generally unnecessary given its linear and predictable dose-serum concentration relationship, lack of drug-drug interactions, and broad therapeutic window. However, there is growing evidence showing that alteration of LEV pharmacokinetics (PK) may occur in special populations calling for the need for TDM. The purpose of this review was to summarize current literature surrounding altered LEV PK in special patient populations and determine if there is a need for levetiracetam TDM. A literature search of MEDLINE (1946 - November 2017) database of available evidence pertaining to altered LEV PK in humans was conducted. A total of 51 articles were found. There has not been a positive correlation shown between LEV levels and efficacy or toxicity. Variable LEV levels are reported in the literature with respect to adverse effects, seizures and efficacy occurring below, within and above the supposed reference ranges. Age is a major contributor to altered pharmacokinetics of LEV as shown in elderly patients and pediatric patients. Compared to adults, clearance of LEV has been shown to be decreased by almost half in patients over 65 and increased by 30-40% in pediatric patients. LEV pharmacokinetics varied further when data from its use in neonates was explored. LEV clearance declined in a linear fashion with declining estimates of creatinine clearance but was variable in patients with end-stage renal failure or those requiring renal replacement therapy. In patients who were critically ill, LEV clearance may be augmented and these patients may require higher doses of medications to maintain drug levels. In patients who are pregnant, LEV levels are likely to decline as pregnancy progresses due to changes in glomerular filtration rate and remain variable in the post-partum period. Routine TDM of levetiracetam is not recommended for all populations, however, it may be beneficial to maintain an individual therapeutic range in patients where the PK of LEV may be altered, such as in patients who are critically ill patients, pregnant, pediatrics or elderly.


Hospitalization for pneumonia in the Finnish working-age population.
The aim of this investigation was to describe the use of hospital services among the Finnish working-age population aged 15 to 64 years on account of pneumonia. The study was based on nationwide hospital discharge records maintained by the National Research and Development Centre for Welfare and Health. Pneumonia caused 63,414 periods of hospital treatment and a total of 568,861 hospitalization days among working-age people in Finland from 1984 to 1993. The mean annual age-specific rate of pneumonia-related hospital treatment periods per 1000 persons among men was 2.67 (SD 0.17) and among women 1.10 (SD 0.08). The men had more treatment periods than the women in every 5-year age group, the greatest difference being in the youngest age groups and in the oldest ones. In men the mean annual rate of treatment periods increased rapidly after the age of 40 years (from 1.54 per 1000 persons in age group 40-45 years to 7.86 per 1000 in age group 60-64 years). In women the increase in corresponding age groups was more moderate (from 0.77 to 3.19). The increasing number of pneumonia-related hospital treatment periods after the age of 40 is facing the challenge for the occupational health care in the future.


[Incidence of emesis in outpatients on chemotherapy for breast cancer and the clinical efficacy of ondansetron hydrochloride tablets].
The incidence of nausea and vomiting was investigated for a maximum of 7 days in 32 breast cancer patients receiving CAF (cyclophosphamide, adriamycin, 5-fluorouracil) and CMF (cyclophosphamide, methotrexate, 5-fluorouracil) therapies. For those patients who experienced nausea and vomiting, 4 mg/day of ondansetron hydrochloride (OND) in tablet form was given in the next course of the chemotherapy, and the anti-emetic effect of the drug was examined. During the observation period, nausea was seen in 17.2-50.0% of the patients and vomiting in 3.1-15.6%. The number of patients who had nausea and vomiting was 22. The anti-emetic effect was examined in 18 out of 22 cases with nausea and vomiting. An anti-emetic effect based on the judgement criterion (efficacy rate) was seen in 94.4% or more of patients for all the days of observation. A marked effect was seen in higher proportion of patients. In conclusion, nausea and vomiting occurred in 17.2-50.0% of the breast cancer patients on chemotherapy (CAF and CMF therapies). To improve the QOL of those patients, anti-emetic treatment using OND tablets as necessary is considered to be effective.


Cytokine dysregulation despite immunoglobulin replacement therapy in common variable immunodeficiency (CVID).
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. CVID is a heterogeneous disorder with a presumed multifactorial etiology. Intravenous or subcutaneous immunoglobulin replacement therapy (IgRT) can prevent severe infections but not underlying immune dysregulation. In this study, we evaluated the serum concentrations of proinflammatory (TNF-α, IL-1β, IL-6) and immunoregulatory cytokines (IL-10), as well as lipopolysaccharide (LPS) and soluble CD14 (sCD14) in CVID individuals with infectious only (INF-CVID), and those with additional systemic autoimmune and inflammatory disorders (NIC-CVID), and healthy donors (HD). Our results showed increased serum concentrations of TNF-α, IL-1β, IL-6, and IL-10 in both INF-CVID and NIC-CVID subjects compared to HD. However, elevations of TNF-α, IL-1β, IL-6, and IL-10 were significantly more marked in NIC-CVID than INF-CVID. Additionally, LPS concentrations were increased only in NIC-CVID but not in INF-CVID compared to HD. Circulating levels of sCD14 were significantly increased in NIC-CVID compared to both INF-CVID and HD. These findings indicate persistent cytokine dysregulation despite IgRT in individuals with CVID. Moreover, the circulating cytokine profile reveals the heterogeneity of immune dysregulation in different subgroups of CVID subjects.


Delayed neurotoxicity after ingestion of carbamate pesticide.
We studied a patient who ingested 27 gm (500 mg/kg) of carbaryl (1-naphthyl N-methylcarbamate), a popular carbamate pesticide. After he recovered from acute cholinergic toxicity, acute weakness of arms and legs was accompanied by electrophysiologic findings consistent with axonal peripheral neuropathy. Recovery began at 1 week and continued for 9 months. A similar delayed neuropathy has been described with organophosphates but not with carbamate insecticides.


Order-chaos transition in correlation diagrams and quantization of period orbits.
Eigenlevel correlation diagrams has proven to be a very useful tool to understand eigenstate characteristics of classically chaotic systems. In particular, we showed in a previous publication [Phys. Rev. Lett. 80, 944 (1998)0031-900710.1103/PhysRevLett.80.944] how to unveil the scarring mechanism, a cornerstone in the theory of quantum chaos, using the Planck constant as the correlation parameter. By increasing the Planck constant, we induced a transition from order to chaos, in which scarred wave functions appeared as the interaction of pairs of eigenstates in broad avoided crossings, forming a well-defined frontier in the correlation diagram. In this paper, we demonstrate that this frontier can be obtained by means of the semiclassical quantization of the involved scarring periodic orbits. Additionally, in order to calculate the Maslov index of each scarring periodic orbit, which is necessary for the semiclassical quantization procedure, we introduce a straightforward method based on Lagrangian descriptors. We illustrate the theory using the vibrational eigenstates of the LiCN molecular system.


Overexpression of miR-15b-5p promotes gastric cancer metastasis by regulating PAQR3.
Gastric cancer (GC) is the fifth most common cancer in the world, with 952,000 new cases diagnosed in 2012. Tumor metastasis is the major cause of cancer recurrence and death. miR-15b-5p has been reported to be dysregulated in numerous types of cancers. However, the role of miR-15b-5p in GC metastasis remains unclear. An miRNA microarray was adopted to analyze the miRNA expression profile. By employing quantitative real-time polymerase chain reaction (qRT-PCR), miR-15b-5p expression levels were detected in GC cell lines, tissues and plasma samples. In addition, the effects of miR-15b-5p on cell proliferation, migration and invasion were studied by applying gain-of-function approaches. Moreover, the target of miR-15b-5p was assessed by dual-luciferase assay, and the mechanism underlying the regulation of GC metastasis by miR-15b-5p was assessed by rescue experiments. The results revealed that miR-15b-5p was upregulated in GC cell lines, tissues and plasma samples. A high plasma level of miR-15b-5p was correlated with distant tumor metastasis. In addition, overexpression of miR‑15b-5p in GC cells promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition (EMT). Moreover, progestin and adipoQ receptor family member 3 (PAQR3) was found to be a direct target of miR-15b-5p and re-expression of PAQR3 in miR-15b-5p-overexpressing GC cells partly attenuated the proliferation, migration and invasion. These findings revealed that miR-15b-5p promotes the metastasis of GC cells through PAQR3 and may represent a potential biomarker of GC.


Use of bladder volume measurement assessed with ultrasound to predict postoperative urinary retention.
Postoperative urinary retention (POUR) is a common complication after spinal anesthesia. Ultrasound (US) is a simple, non-invasive method to estimate bladder volume before and after surgery. Primary aim of the present study was to investigate utility of bladder volume measured before and after surgery in prediction of POUR risk. Secondary aim was to investigate necessity of urethral catheter use and risk of urethral catheter-related infections. Eighty patients who received spinal anesthesia for arthroscopic knee surgery were included in the study. Level and duration of sensory and motor block; bladder volume measured preoperatively, in post-anesthetic care unit (PACU), and when discharged from PACU; use of urethral catheter; and incidence of urinary tract infection data were recorded. POUR was observed in 28.7% of patients. Length of time for sensory block regression was significantly shorter in patients without POUR (p=0.012). Spontaneous urination was not observed in 3 of 23 patients with POUR, although bladder volume was less than 600 mL. Bladder volume over 600 mL without urination was recorded in 20 patients. There was no statistical difference in preoperative bladder volume between patients who did or did not develop POUR. Bladder volume on admission to PACU was higher in patients with POUR (p=0.023). Urgency and dysuria were observed in 5 patients who required urethral catheterization during postoperative period. Urinary tract infection developed in 1 patient. There was no statistical difference in development of urinary tract infection between patient groups who did and did not undergo urethral catheterization. Assessment of patient bladder volume with US before arthroscopic knee surgery may be used to foresee development of POUR. Avoiding elective urinary catheterization may reduce urinary infections.


A rare anatomical variation of the biliary tree.
A 31-year-old woman was admitted to our department in order to undergo a laparoscopic cholecystectomy. The operation was converted to open due to cholorrhea during the dissection in the hepatocystic triangle. The cholorrhea came from a transected bile duct, which was 2 mm in diameter, came out of the hepatoduodenal ligament, ran along the common hepatic duct and drained into the cystic duct, in proximity to the neck of the gallbladder. The gallbladder was removed and an intraoperative cholangiography revealed that the aberrant bile duct was originated from the right posterior sectoral duct (RPSD). The RPSD continued its typical course up to its confluence with the right anterior sectoral duct and the formation of the right hepatic duct. This is a rare type of aberrant bile duct, which is added to the long catalogue of the anatomical variations of the biliary tree.


Influence of leaf age, species and soil depth on the authenticity and geographical origin assignment of green tea.
Stable isotope fractionation occurring during leaf growth provides internal characteristics for identifying the geographical origin, traceability and authentication of tea. Studying the influence of leaf age, species and the relationship with the cultivated soil may reveal previously undocumented stable isotope fractionation mechanisms, and provide a deeper understanding of the physiological isotopic effects on the tractability and authentication accuracy of green tea to combat mislabeling and fraudulent conduct. A total of 36 pairs of young (one bud with one leaf) and mature growth (older leaf) samples from two species of Longjing tea (Longjing #43 and Colonial cultivar) and corresponding cultivation soil samples from two different depth layers (0-20 cm and 20-40 cm) were collected in Westlake district, Hangzhou, Zhejiang province, China. Four stable isotope ratios (δ13 C, δ15 N, δ2 H, and δ18 O values) were measured using an elemental analyzer coupled with an isotope ratio spectrometer. Linear correlation and one-way analysis of variance (ANOVA) statistical analyses were performed to investigate isotopic fractionation mechanisms during plant growth, and reflect the dynamic physiological processes from soil to leaf. The carbon and nitrogen isotope ratios (δ13 C and δ15 N values) reflected the absorption, migration and fractionation of carbon dioxide and nitrogenous nutrients during photosynthesis, nutrient uptake, nitrogen fixation and leaf respiration. The water isotope ratios (δ2 H and δ18 O values) reflected the use and fractionation of water by tea plants at different growth stages. Considerable differences were found for hydrogen and oxygen isotope ratios according to leaf age, revealing complex isotopic fractionation mechanisms and possible interference factors. Leaf maturity effects should be considered, as they will influence the precision and accuracy of models when assigning the geographical origin, traceability and authentication of tea.


Innervation of the muscle of the bladder in the rat.
A quantitative ultrastructural analysis of the organisation and terminal density of the nerves associated with the muscle of the body of the bladder was undertaken in the rat. The results obtained were suggestive of the organisation of the intramuscular plexuses into 2 separate and possibly functionally distinct networks. The nerves ramifying within the muscle fascicles mostly contained between 1 and 3 axons and on the basis of counts made in 12 animals, appeared to provide the muscle with only a moderate level of innervation. Although adrenergic terminals were frequently seen in the perivascular plexuses, they were rarely encountered in the nerves within the muscle fascicles. The majority of the terminals in the intrafascicular nerves were similar to those normally classified as cholinergic and, in many, the exposed parts of the axonal membrane were closely related to that of adjacent muscle cells. In addition to clear vesicles and large dense-cored vesicles, many of these terminals contained scattered small dense-cored vesicles. It was suggested that the involvement of the material present in the small dense-cored vesicles with acetylcholine in impulse transmission might account for the atypical features of such transmission in the bladder and in particular its resistance to blockade by atropine. The nerves forming the interfascicular networks contained few axons with cholinergic terminals, and were characterised by much larger numbers of a morphologically distinctive type of terminal. Some of these were indistinguishable from those recently defined as the terminals of purinergic axons but their distribution in the nerves suggests that they represent the terminals of afferent axons and is consistent with the concept that, together with those observed in other tissues, such axons are involved in pain perception.


A randomized comparison of the MCRI On-X and CarboMedics Top Hat bileaflet mechanical replacement aortic valves: early postoperative hemodynamic function and clinical events.
This study compared hemodynamic function and clinical events in consecutive patients randomly assigned to receive a wholly supra-annular replacement valve or a valve with an intra-annular component. Fifty-two patients with an average age of 62 years (range 40-74 years) were sized for both a CarboMedics Top Hat valve (CarboMedics Inc, Austin, Tex) and an MCRI On-X valve (Medical Carbon Research Institute, LLC, Austin, Tex) before random assignment to receive either valve type. Echocardiographic and clinical assessments were performed in the immediate postoperative period and at 1 year. The mean effective orifice areas were 1.41 +/- 0.42 cm2 for the Top Hat and 2.17 +/- 0.78 cm2 for the On-X (P < .0001). The mean pressure differences were 12.2 +/- 4.4 mm Hg and 6.9 +/- 3.6 mm Hg, respectively (P < .0001). New York Heart Association functional class was better with the On-X than the Top Hat valves, but there were no differences in clinical events, regression of left ventricular mass, or measures of hemolysis. The partially intra-annular MCRI On-X valve was hemodynamically superior to the wholly supra-annular CarboMedics Top Hat valve. However, there were no differences in early clinical outcomes between the two valve types.


Selective increases of procoagulant activity in rabbit lymphoid populations in vitro following stimulation with endotoxin: dependence on anatomic source.
Rabbit mononuclear leukocytes isolated from a variety of anatomic sites were examined for ability to generate procoagulant activity in vitro. Marrow, blood and spleen mononuclear cell populations were found to differ functionally from lymph node, thymus and alveolar populations by having much greater ability to increase in tissue factor activity in response to an endotoxin stimulus. Thus, after incubation in the presence of endotoxin, leukocytes obtained from marrow, blood, and spleen were found to increase in procoagulant activity characterized as tissue factor by 832, 1942 and 12.6 fold, respectively. In contrast, pulmonary alveolar macrophages increased in tissue factor activity only by 2.8 fold, and lymph node and thymus mononuclear cells showed little or no increases. These functional differences, demonstrated by exposing the six cell populations to endotoxin under controlled conditions in vitro, likely explain the similar pattern of anatomic selectivity of leukocyte tissue factor increases reported to occur in vivo during endotoxemia and Shwartzman reactions (1).


Highly Stable MWCNT@NVP Composite as a Cathode Material for Na-Ion Batteries.
A 3D framework with Nasicon structured polyanionic Na3V2(PO4)3 (NVP) has been emphasized as a leading cathode material for sodium-ion batteries (SIBs) due to its high working voltage plateau, structural stability, and good rate performance. Herein, pristine NVP and MWCNT@NVP composite synthesized via a facile solid-state method are examined and compared as cathode materials for Na-ion batteries. The morphological study confirms the uniform distribution of MWCNTs in the pristine NVP structure. Impedance spectroscopy clearly confirms more diffusion of Na ions for the MWCNT@NVP composite as compared to pristine NVP, considering its diffusion coefficient which directly implies on an increase in specific capacity. MWCNT@NVP (FNV-2) showed specific discharge capacity 110 mAhg-1 at 0.1C current rate which is almost stable at higher current rates with marginal fading. However, the pristine NVP shows capacity loss at a higher current rate. It is noteworthy that the MWCNT@NVP composite shows stable performance with marginal specific capacity fading (1%) compared to pristine (15%). This is because of the mechanical integrity and stability afforded to the composite by the intertwined MWCNT framework in the MWCNT@NVP composite matrix against electrode degradation during the electrochemical reaction. More significantly, even at a higher current rate, that is, at 10 C, the composite recorded a very stable and excellent Columbic efficiency of 97% with a reversible specific capacity of 94 mAhg-1 after 2000 cycles. An enhanced electrochemical performance, that is, rate capability and cycling stability, demonstrates the high potential of the MWCNT@NVP composite for Na-ion storage. Moreover, a sodium-ion full cell with hard carbon demonstrated a reversible capacity of 103 mAhg-1 at C/20 current rate, which clearly demonstrates that MWCNT@NVP is a promising cathode material for sodium-ion batteries.


[HIV-related multiple non-Hodgkin lymphomas].
A 35-year-old man was admitted with continuous general fatigue and low grade fever. He was HIV-positive, and had gastric diffuse large B-cell lymphoma and renal T-cell anaplastic large cell lymphoma (T-ALCL). We diagnosed double lymphomas related to AIDS. The patient received anti-retroviral therapy, and started the CHOP regimen for the double lymphomas, resulting in transient improvement. However, fever again appeared during HAART and CHOP treatment, and a right inguinal subcutaneous lesion appeared. Biopsy specimen demonstrated null cell ALCL, and this patient demonstrated multiple lymphomas. This case suggested that cancer generation was promoted by low immunity, although it is known that ambivalent tumors such as non-Hodgkin lymphomas can occur frequently.


Utility of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Cardiac Infections.
Diagnosis of cardiac infections, which includes infective endocarditis (IE) and cardiac device infections, despite having a high death rate, is still challenging. Frequently used modalities such as echocardiography, computed tomography (CT), and magnetic resonance imaging cannot confirm the presence of an active infection or extracardiac findings. Taking these things to consideration, newer guidelines have suggested the inclusion of 18F fluorodeoxyglucose positron emission tomography/CT (18F FDG PET/CT) in the workup of patients with suspected prosthetic valve IE. In this pictorial essay, we are demonstrating the utility of 18F-FDG PET/CT in varied cases of IE, cardiac implantable electronic devices, and coronary stent infection and how they helped in solving diagnostic dilemmas.


Isolation and partial polypeptide characterization of bovine neutrophil plasma membranes.
The neutrophil plasma membrane has a major role in migration, phagocytosis, and destruction of microorganisms. Neutrophils isolated from blood and mammary secretions were homogenized, and the plasma membrane fraction was isolated on discontinuous sucrose gradient (20, 32, and 50%). Purity of plasma membrane preparation was determined by use of marker enzyme analysis. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the membrane proteins was performed under reducing conditions for polypeptide characterization. The membrane proteins were also labeled with 125I externally, using 1,3,4,6-tetrachloro-3 alpha-6 alpha-diphenylglycouril, and proteins were separated by SDS-PAGE and autoradiographed. Compared with whole cell homogenate, the plasma membrane fraction obtained at the 20/32% interface was enriched for the marker enzymes, 5'-nucleotidase (16-fold), alkaline phosphatase (5.5-fold), and total phosphatase (26-fold). The membrane fraction had minimal specific activity for beta-glucuronidase (0.4-fold), compared with whole cell homogenate. Plasma membrane protein yield was about 500 micrograms/10(9) bovine blood neutrophils. The SDS-PAGE of plasma membrane proteins revealed 25 protein bands, of which 13 were major bands. There were 3 distinct bands (18, 36, and 65 kd) in the plasma membrane-enriched fraction (20/32 interface) that were not seen in other fractions (30/50% and pellet). Further, 125I-labeling identified 5 distinct protein bands (205, 140, 65, 35, and 30 kd). Blood and mammary neutrophils had similar polypeptide patterns, except that 36- and 65-kd bands were more prominent for blood neutrophils than for mammary neutrophils.


Intrapleural instillation of streptokinase. Effects on systemic fibrinolysis.
Ten consecutive patients aged 25 to 75 with postoperative empyema or hemothorax conventionally treated with drainage without sufficient effect were given intrapleural instillations of streptokinase (Kabikinase, 250,000 IE) for 4 hours). The effects on systemic fibrinolysis were studied. Venous blood samples for determination of fibrinolytic activity on fibrin plates, plasminogen, alpha 2-antiplasmin, alpha 2-macroglobulin, fibrinogen, fibrin(ogen) degradation products (FDP) and thrombin time were taken before instillation, after instillation and then after 24 hours. Preinstillation values were compared to the values 4 and 24 hours after instillation with Student's paired t-test. There were no differences in fibrinolytic activity, alpha 2-macroglobulin and thrombin time. There was a slight increase in plasminogen, alpha 2-antiplasmin and fibrinogen, probably due to an acute phase reaction. Fibrin degradation products showed an increase with border line significance. These changes are not consistent with generalized fibrinolysis, and it is concluded that intrapleural instillations of streptokinase can be given safely in the early posttraumatic or postoperative period.


An Overview of New Possible Treatments of Alzheimer's Disease, Based on Natural Products and Semi-Synthetic Compounds.
Dementias and all related neurodegenerative diseases of the Central Nervous System (CNS) are a current issue arousing a great deal of interest in the international scientific community. This is due to the increasing number of patients suffering from these diseases. These pathologies represent a serious problem, not only concerning the quality of life of the patient, but in addition, the enormous economic efforts that society has to do for their treatment. There are currently a few strategies that are available in order to prevent the progression or to mitigate symptoms of the aforementioned diseases. This consideration is particularly true if we consider the specific pathology of Alzheimer's Disease (AD). We performed a literature search for peer-reviewed articles using different databases, such as PubMed or Scopus, and exploiting different keywords and different logical operators. Ninety-eight papers were included in the review. Four papers give an overview of the background of the dementias all over the world. The remaining papers are focused on new possibilities of treatment with natural and semi-synthetic compounds for AD. The aim of this review is to give an overview of new and promising natural products and semi-synthetic compounds which could represent a source of "lead compounds" for the development of new potential drugs that could be a valid therapeutic strategy for the treatment of this pathology.


Dynamic Notch Signaling Specifies Each Cell Fate in Drosophila Spermathecal Lineage.
Spermathecae are glandular organs in the insect female reproductive tract that play essential roles in insect reproduction; however, the molecular mechanism involved in their development is largely unknown. Drosophila spermathecae consist of class-III secretory units, in which each secretory cell (SC) discharges its products to the central lumen through an end-apparatus and a canal. Secretory unit formation in Drosophila spermathecae utilizes a fixed cell lineage, in which each secretory unit precursor (SUP) divides to produce one pIIb cell and one pIIa cell. The former differentiates into an apical cell (AC), whereas the latter divides again to produce an SC and a basal cell (BC). It is unclear how each cell acquires its identity and contributes to secretory unit formation. Here, we demonstrate that Notch signaling is required and sufficient for the specification of lumen epithelial precursors (LEPs; vs. SUPs), pIIb (vs. pIIa), and SCs (vs. BCs) sequentially. To our surprise, Notch activation in LEPs and SCs apparently utilizes different ligand mechanisms. In addition, Notch signaling both suppresses and activates transcription factors Hindsight (Hnt) and Cut during spermathecal lineage specification, supporting the notion that Notch signaling can have opposite biological outcomes in different cellular environments. Furthermore, LEP-derived epithelial cells (ECs) and ACs show distinct cellular morphology and are essential for securing secretory units to the epithelial lumen. Our work demonstrates, for the first time, the dynamic role of Notch signaling in binary cell fate determination in Drosophila spermathecae and the role of ECs and ACs in secretory unit formation.


Revisiting the hallmarks of cancer.
The hallmarks of cancer described by Hanahan and Weinberg have proved seminal in our understanding of cancer's common traits and in rational drug design. Not free of critique and with understanding of different aspects of tumorigenesis coming into clearer focus in the recent years, we attempt to draw a more organized and updated picture of the cancer hallmarks. We define seven hallmarks of cancer: selective growth and proliferative advantage, altered stress response favoring overall survival, vascularization, invasion and metastasis, metabolic rewiring, an abetting microenvironment, and immune modulation, while highlighting some considerations for the future of the field.


Immunopathologic studies in pityriasis lichenoides.
Skin biopsy specimens from five patients with pityriasis lichenoides et varioliformis acuta and from six patients with pityriasis lichenoides chronica were studied by direct immunofluorescence and by an immunoperoxidase technique using a panel of monoclonal antibodies. The dermal inflammatory infiltrate was composed of T cells, macrophages, and a small proportion of CD1a+ cells, mostly perivascular. CD8+ cells (cytotoxic/suppressor phenotype) predominated in the epidermis according to the degree of epidermal necroses, whereas CD4+ cells (helper/inducer phenotype) were superior in number among dermal T cells. A few B cells and Leu7+ cells were detected in only a small proportion of lesions. The results obtained confirm that the two conditions are variants of a single disease process and suggest that cell-mediated immune mechanisms may be important in the pathogenesis of the epidermal and vascular damage. Endothelial cells (HLA-DR+ and HLA-DQ+) and CD1a+ cells (epidermal and possibly dermal) could be primarily involved, acting as antigen-presenting cells.


Synthesis of Enantiomerically Pure 1,2,3-Trisubstituted Cyclopropane Nucleosides Using Pd-Catalyzed Substitution via Directing Group-Mediated C(sp3)-H Activation as a Key Step.
A series of enantiomerically pure 1,2,3-trisubstituted cyclopropane nucleosides Ia-Id and IIa-IId of medicinal chemical interest was designed and synthesized. In the synthesis, a Pd-catalyzed substitution reaction via a directing group-mediated C(sp3)-H activation was effectively used to construct the 1,2,3-trisubstituted cyclopropane structure as a key step.


Identification and characterisation of enteroaggregative Escherichia coli subtypes associated with human disease.
Enteroaggregative E. coli (EAEC) are a major cause of diarrhoea worldwide. Due to their heterogeneity and carriage in healthy individuals, identification of diagnostic virulence markers for pathogenic strains has been difficult. In this study, we have determined phenotypic and genotypic differences between EAEC strains of sequence types (STs) epidemiologically associated with asymptomatic carriage (ST31) and diarrhoeal disease (ST40). ST40 strains demonstrated significantly enhanced intestinal adherence, biofilm formation, and pro-inflammatory interleukin-8 secretion compared with ST31 isolates. This was independent of whether strains were derived from diarrhoea patients or healthy controls. Whole genome sequencing revealed differences in putative virulence genes encoding aggregative adherence fimbriae, E. coli common pilus, flagellin and EAEC heat-stable enterotoxin 1. Our results indicate that ST40 strains have a higher intrinsic potential of human pathogenesis due to a specific combination of virulence-related factors which promote host cell colonization and inflammation. These findings may contribute to the development of genotypic and/or phenotypic markers for EAEC strains of high virulence.


Tunable electronic structures and half-metallicity in two-dimensional InSe functionalized with magnetic superatom.
Based on first-principles calculations, we investigate the geometric, energetic and electronic properties of two-dimensional (2D) InSe functionalized with magnetic superatoms (MnCl3). As a nonmagnetic semiconductor, 2D InSe exhibits non-covalent interaction with MnCl3 and provides an ideal substrate for the assembly of magnetic superatoms. We show that with a low coverage of MnCl3, the functionalized system behaves as a magnetic semiconductor with spin-polarized superatomic states residing inside the energy gap of InSe. When the coverage becomes higher, the system has one spin channel crossing Fermi level while the other remains insulating, thus being half-metallic. We further demonstrate electric field effects on the functionalized system, and reveal that half metal with 100% spin polarization can be achieved at a lower coverage due to the field induced charge transfer, which downshifts the unoccupied bands of one spin component so that they become partially filled. These findings are generally applicable, demonstrating the great promise of combining superatom assembly with electric gating for controllable and versatile 2D spintronics.


Effects of Changing pH, Incubation Time, and As(V) Competition, on F- Retention on Soils, Natural Adsorbents, By-Products, and Waste Materials.
The purpose of this work was to elucidate the repercussion of changing pH, incubation time and As(V) competition on fluoride (F-) sorption on forest and vineyard soil samples, pyritic, and granitic materials, as well as on the by-products pine sawdust, oak wood ash, mussel shell ash, fine and coarse mussel shell, and slate processing waste fines. To reach this end, the methodological approach was based on batch-type experiments. The results indicate that, for most materials, F- sorption was very high at the start, but was clearly diminished when the pH value increased. However, oak wood ash and shell ash showed high F- sorption even at alkaline pH, and pine sawdust showed low F- sorption for any pH value. Specifically, F- sorption was close to 100% for both ashes at pH < 6, and around 70% at pH 10, while for forest soil it was close to 90% at pH < 2, and around 60% at pH values near 8. Regarding the effect of incubation time on F- sorption, it was very low for both soils, pyritic material, granitic material, and both kinds of ashes, as all of them showed very rapid F- sorption from the start, with differences being lesser than 10% between sorption at 30 min and 1 month of incubation. However, sawdust and slate fines sorbed 20% of added F- in 30 min, remaining constant up to 12 h, and doubling after 30 days. And finally, mussel shell sorbed 20% at 30 min, increasing to close to 60% when incubation time was 30 days. This means that some of the materials showed a first sorption phase characterized by rapid F- sorption, and a slower sorption in a second phase. As regards the effect of the presence of As(V) on F- sorption, it was almost negligible, indicating the absence of competition for sorption sites. In view of that all, these results could aid to appropriately manage soils and by-products when focusing on F- removal, in circumstances where pH value changes, contact time vary from hours to days, and potential competition between F- and As(V) could take place.