Effects of Emerging Alcohol and Marijuana Use Behaviors on Adolescents' Neuropsychological Functioning Over Four Years.
Adolescence is a period of neuromaturation concomitant with increased substance involvement. Most substance use studies of adolescents have focused on categorical classifications (e.g., dependent vs. nondependent), but little is known about the influence of specific substance use behaviors on cognitive functioning in youth. This study prospectively evaluated the quantitative effects of different substance use behaviors on neuropsychological functioning. A cognitive test battery was administered at baseline (ages 12-14 years), before substance use initiation, and at follow-up (M = 4.0 years, SD = 2.0) to evaluate changes in verbal memory, visuospatial ability, psychomotor speed, processing speed, and working memory. Robust regressions examined substance use behaviors as predictors of neuropsychological functioning (N = 234). Several substance use behaviors predicted follow-up neuropsychological functioning above and beyond effects of baseline performance on the same measure (ps < .05). Specifically, more alcohol use days predicted worse verbal memory (β = -.15) and visuospatial ability (β = -.19). More postdrinking effects (β = -.15) and greater drug use (β = -.11) predicted worse psychomotor speed. Processing speed was not predicted by substance involvement (ps > .05). Unexpectedly, more alcohol use predicted better working memory performance (β = .12). The frequency and intensity of adolescent alcohol use may be more intricately linked to neuropsychological outcomes than previously considered. The low prevalence of substance use disorder in the sample suggests that subdiagnostic users may still experience adverse effects to verbal memory, visuospatial functioning, and psychomotor speed after initiating intense or frequent alcohol use.


The murine H19 gene is activated during embryonic stem cell differentiation in vitro and at the time of implantation in the developing embryo.
The differentiation in vitro of murine embryonic stem cells to embryoid bodies mimics events that occur in vivo shortly before and after embryonic implantation. We have used this system, together with differential cDNA cloning, to identify genes the expression of which is regulated during early embryogenesis. Here we describe the isolation of several such cDNA clones, one of which corresponds to the gene H19. This gene is activated in extraembryonic cell types at the time of implantation, suggesting that it may play a role at this stage of development, and is subsequently expressed in all of the cells of the mid-gestation embryo with the striking exception of most of those of the developing central and peripheral nervous systems. After birth, expression of this gene ceases or is dramatically reduced in all tissues.


Hepatic α-tocopherol transfer protein: ligand-induced protection from proteasomal degradation.
There are eight naturally occurring forms of the dietary antioxidant vitamin E. Of these, only α-tocopherol is retained at high levels in vertebrate plasma and tissues. This selectivity is achieved in part by the action of the hepatic α-tocopherol transfer protein (TTP), which facilitates the selective incorporation of dietary α-tocopherol into circulating lipoproteins. We examined the effects of vitamin E on TTP expression in cultured hepatocytes. Treatment with vitamin E precipitated a time- and dose-dependent increase in the steady-state levels of TTP. This stabilization was caused by α-tocopherol-induced attenuation of the ubiquitination of TTP and its subsequent degradation by the proteasome. In vitro, vitamin E protected TTP from proteolytic degradation by trypsin, suggesting ligand-induced changes in protein conformation. Cell fractionation studies showed that TTP is distributed between the cytosolic and membranous organelle fraction, and that tocopherol induced the translocation of some TTP from the cytosol to the organelle fraction. Furthermore, vitamin E markedly attenuated the degradation of organelle-bound TTP. These findings suggest that vitamin E imparts a distinct conformation on TTP that is associated with localization to a specific cellular compartment, where the protein is less susceptible to proteasomal degradation.


Loading of a unilateral temporomandibular joint prosthesis: a three-dimensional mathematical study.
The load on the prosthetic side and the influence of the design on the remaining natural contralateral TMJ must be known before a unilateral temporomandibular joint (TMJ) prosthesis can be developed. The aim of the present study was to determine the maximum loading of the TMJ prosthetic side and the natural contralateral TMJ and to investigate the influence of the location of the center of rotation of the prosthesis on the maximum loading. For this purpose, a mathematical model of the mandible with a unilateral TMJ prosthesis with a fixed center of rotation (CR) was developed. The location of the CR of the TMJ prosthesis was varied from the middle of the natural mandibular condyle to 15 mm inferior to this location. Although the maximum joint reaction forces changed as a result of a unilateral TMJ prosthesis, the trend of the loading curves was similar to that of an intact mandible. A unilateral TMJ prosthesis resulted in a 50% higher loading of the prosthetic side, while the load on the natural contralateral TMJ remained within normal limits. The maximum load on the prosthetic side occurred during molar bites and could reach 100 N in the cranial direction, 30 N in the ventral direction, and 25 N in the medio-lateral direction. The location of the CR did not have a significant influence on the loading of the TMJ prosthesis and the natural contralateral TMJ.


Small Scale Production of Recombinant Adeno-Associated Viral Vectors for Gene Delivery to the Nervous System.
Adeno-associated viral vectors have numerous applications in neuroscience, including the study of gene function in health and disease, targeting of light-sensitive proteins to anatomically distinct sets of neurons to manipulate neuronal activity (optogenetics), and the delivery of fluorescent protein to study anatomical connectivity in the brain. Moreover several phase I/II clinical trials for gene therapy of eye and brain diseases with adeno-associated viral vectors have shown that these vectors are well tolerated by human patients. In this chapter we describe a detailed protocol for the small scale production of recombinant adeno-associated viral vectors. This protocol can be executed by investigators with experience in cell culture and molecular biological techniques in any well-equipped molecular neurobiology laboratory. With this protocol we typically obtain research batches of 100-200 μL that range in titer from 5 × 1012 to 2 × 1013 genomic copies/mL.


Acoustic shock wave propagation in a heterogeneous medium: a numerical simulation beyond the parabolic approximation.
Numerical simulation of nonlinear acoustics and shock waves in a weakly heterogeneous and lossless medium is considered. The wave equation is formulated so as to separate homogeneous diffraction, heterogeneous effects, and nonlinearities. A numerical method called heterogeneous one-way approximation for resolution of diffraction (HOWARD) is developed, that solves the homogeneous part of the equation in the spectral domain (both in time and space) through a one-way approximation neglecting backscattering. A second-order parabolic approximation is performed but only on the small, heterogeneous part. So the resulting equation is more precise than the usual standard or wide-angle parabolic approximation. It has the same dispersion equation as the exact wave equation for all forward propagating waves, including evanescent waves. Finally, nonlinear terms are treated through an analytical, shock-fitting method. Several validation tests are performed through comparisons with analytical solutions in the linear case and outputs of the standard or wide-angle parabolic approximation in the nonlinear case. Numerical convergence tests and physical analysis are finally performed in the fully heterogeneous and nonlinear case of shock wave focusing through an acoustical lens.


Coronavirus infections in children: from SARS and MERS to COVID-19, a narrative review of epidemiological and clinical features.
Emerging and re-emerging viruses represent an important challenge for global public health. In the 1960s, coronaviruses (CoVs) were recognized as disease agents in humans. In only two decades, three strains of CoVs have crossed species barriers rapidly emerging as human pathogens resulting in life-threatening disease with a pandemic potential: severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002, Middle-East respiratory syndrome coronavirus (MERS-CoV) in 2012 and the recently emerged SARS-CoV-2. This narrative review aims to provide a comprehensive overview of epidemiological, pathogenic and clinical features, along with diagnosis and treatment, of the ongoing epidemic of new coronavirus disease 2019 (COVID-19) in the pediatric population in comparison to the first two previous deadly coronavirus outbreaks, SARS and MERS. Literature analysis showed that SARS-CoV, MERS-CoV and SARS-CoV-2 infections seem to affect children less commonly and less severely as compared with adults. Since children are usually asymptomatic, they are often not tested, leading to an underestimate of the true numbers infected. Most of the documented infections belong to family clusters, so the importance of children in transmitting the virus remains uncertain. Like in SARS and MERS infection, there is the possibility that children are not an important reservoir for novel CoVs and this may have important implications for school attendance. While waiting for an effective against SARS-CoV-2, further prevalence studies in paediatric age are needed, in order to clarify the role of children in different age groups in the spread of the infection.


Selective transport of divalent cations by transition metal permeases: the Alcaligenes eutrophus HoxN and the Rhodococcus rhodochrous NhlF.
nhlF and hoxN, the genes encoding a cobalt transporter of Rhodococcus rhodochrous J1 and a nickel permease of Alcaligenes eutrophus H16, respectively, were expressed in Escherichia coli. 57CO2+ and 63Ni2+ transport of the recombinants was examined by means of a previously described physiological assay. Although the transporters are highly similar, different preferences for divalent transition metal cations were observed. HoxN was unable to transport 57CO2+, but mediated 63Ni2+ uptake. The latter activity was unaffected by a tenfold excess of other divalent cations, showing the specificity of HoxN for Ni2+. In contrast, NhlF transported both 57CO2+ and 63Ni2+ ion. NhlF-mediated 63Ni2+ uptake was markedly reduced in the presence of CO2+, while 57CO2+ uptake was only slightly lower in the presence of Ni2+. These results indicate different affinities of NhlF for CO2+ and Ni2+ and identified CO2+ ion as the preferred substrate.


Effects of anticoagulation intensity on hemostatic markers in patients with non-valvular atrial fibrillation.
Elevation of hemostatic markers may account for the increased risk of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). The aim of this study was to determine the effects of anticoagulation intensity on hemostatic markers in patients with NVAF. In 509 patients with NVAF, comprising 263 patients treated with warfarin and 246 patients without warfarin, the hemostatic markers of prothrombin fragment F1.2 (F1.2), fibrin D-dimer, platelet factor 4 (PF4), and beta-thromboglobulin were determined and compared with those in 111 patients with sinus rhythm. F1.2 was inversely related with anticoagulation intensity and D-dimer increased with age. All hemostatic markers, except F1.2, were greater in patients with NVAF than in patients with sinus rhythm. F1.2 and D-dimer were significantly lower in patients with international normalized ratio (INR) > or =1.5 than in NVAF patients without warfarin and were not different between NVAF patients with INR of 1.5-1.9 and with INR > or =2.0. Low intensity of anticoagulation (INR 1.5-1.9) suppresses the elevated concentration of F1.2 and D-dimer in patients with NVAF, and might be favorable in Japanese patients with NVAF in view of the balance between prevention of thromboembolism and the adverse effect by warfarin (ie, bleeding).


Discordant Values in Lower Extremity Physiologic Studies Predict Increased Cardiovascular Risk.
Background Ankle-brachial indexes (ABI) are a noninvasive diagnostic tool for peripheral arterial disease and a marker of increased cardiovascular risk. ABI is calculated using the highest systolic blood pressure of the 4 ankle arteries (bilateral dorsalis pedis and posterior tibial). Accordingly, patients may be assigned a normal ABI when the result would be abnormal if calculated using one of the other blood pressure readings. Cardiovascular outcomes for patients with discordant ABIs are undescribed. Methods and Results We performed a retrospective study of patients who underwent ABI measurement for any indication between January 1996 and June 2018. Those with normal ABIs (1.00-1.39) were included. We compared patients with all 4 normal ABIs (calculated using all 4 ankle arteries; n=15 577, median age 64.0 years, 54.4% men) to those with discordant ABIs (at least 1 abnormal ABI ≤0.99; n=2095, median age 66.0 years, 47.8% men). The outcomes assessed were ischemic stroke, myocardial infarction, and all-cause mortality. Compared with patients with concordant normal ABIs, patients with discordant ABIs were older; women; smoked; and had chronic kidney disease, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, hypertension, or prior stroke. Patients with discordant ABIs had a greater risk of myocardial infarction (hazard ratio [HR], 1.31; 95% CI, 1.10-1.56), ischemic stroke (HR, 1.53; 95% CI, 1.37-1.72), and all-cause mortality (HR, 1.27; 95% CI, 1.16-1.39), including after adjustment for baseline comorbidities. Conclusions Discordant ABI results were associated with an increased risk of myocardial infarction, stroke, and all-cause mortality in the studied population. Clinicians should examine ABI calculations using all 4 ankle arteries to better characterize a patient's cardiovascular risk.


Enzymatic solubilization of brewers' spent grain by combined action of carbohydrases and peptidases.
Brewers' spent grain (BSG), a high-volume coproduct from the brewing industry, primarily contains proteins, barley cell wall carbohydrates, and lignin. To create new possibilities for the exploitation of this large biomass stream, the solubilization of BSG by the combined action of carbohydrases (Depol 740 and Econase) and peptidase (Alcalase and Promod 439) was explored. Hydrolysis protocols were optimized with respect to temperature (influencing both microbial contamination and rate of enzymatic hydrolysis), pH, enzyme dose, order of enzyme addition, and processing time. On the basis of this approach, one- and two-step protocols are proposed taking 4-8 h and yielding combined or separate fractions of hydrolyzed oligosaccharides and liberated hydrolyzed protein. Optimized procedures resulted in the solubilization of >80% of the proteinaceous material, up to 39% of the total carbohydrates, and up to 42% of total dry matter in BSG. Of the original xylan present in BSG, 36% could be solubilized. Sequential and simultaneous treatments with the two enzyme types gave similar results. In sequential processes, the order of the carbohydrase and peptidase treatments had only minor effects on the outcome. Depol 740 released more pentoses than Econase and gave slightly higher overall dry matter solubilization yields.


Enhanced catalytic four-electron dioxygen (O2) and two-electron hydrogen peroxide (H2O2) reduction with a copper(II) complex possessing a pendant ligand pivalamido group.
A copper complex, [(PV-tmpa)Cu(II)](ClO4)2 (1) [PV-tmpa = bis(pyrid-2-ylmethyl){[6-(pivalamido)pyrid-2-yl]methyl}amine], acts as a more efficient catalyst for the four-electron reduction of O2 by decamethylferrocene (Fc*) in the presence of trifluoroacetic acid (CF3COOH) in acetone as compared with the corresponding copper complex without a pivalamido group, [(tmpa)Cu(II)](ClO4)2 (2) (tmpa = tris(2-pyridylmethyl)amine). The rate constant (k(obs)) of formation of decamethylferrocenium ion (Fc*(+)) in the catalytic four-electron reduction of O2 by Fc* in the presence of a large excess CF3COOH and O2 obeyed first-order kinetics. The k(obs) value was proportional to the concentration of catalyst 1 or 2, whereas the k(obs) value remained constant irrespective of the concentration of CF3COOH or O2. This indicates that electron transfer from Fc* to 1 or 2 is the rate-determining step in the catalytic cycle of the four-electron reduction of O2 by Fc* in the presence of CF3COOH. The second-order catalytic rate constant (k(cat)) for 1 is 4 times larger than the corresponding value determined for 2. With the pivalamido group in 1 compared to 2, the Cu(II)/Cu(I) potentials are -0.23 and -0.05 V vs SCE, respectively. However, during catalytic turnover, the CF3COO(-) anion present readily binds to 2 shifting the resulting complex's redox potential to -0.35 V. The pivalamido group in 1 is found to inhibit anion binding. The overall effect is to make 1 easier to reduce (relative to 2) during catalysis, accounting for the relative k(cat) values observed. 1 is also an excellent catalyst for the two-electron two-proton reduction of H2O2 to water and is also more efficient than is 2. For both complexes, reaction rates are greater than for the overall four-electron O2-reduction to water, an important asset in the design of catalysts for the latter.


Pulmonary tuberculosis among patients hospitalised with community-acquired pneumonia in a tuberculosis-prevalent area.
A suburban teaching hospital in a tuberculosis (TB) prevalent area. To evaluate the proportion of pulmonary TB among patients hospitalised with suspected community-acquired pneumonia (CAP), and to develop a diagnostic index for identifying TB among these patients. TB cases confirmed using 1) sputum culture, or 2) both sputum acid-fast bacilli smear and polymerase chain reaction for Mycobacterium tuberculosis, were compared with non-tuberculous CAP by demographic, clinical, laboratory and radiographic information. Using multiple logistic regression analysis, risk factors for TB were identified. A diagnostic index was developed by summing up their simplified regression coefficients. Its performance was checked using c-statistic. TB was the second leading cause of CAP (37/528, 7.0%). Risk factors were initial symptoms >7 days, serum albumin <3.5 g/dl, cavitary/nodular infiltrates and upper lobe involvement (1 point for each). The c-statistic of the index was 0.856 (95%CI 0.789-0.923), and for bootstrapping samples of 1000 repetitions it was 0.856 (95%CI 0.791-0.921). For scores ≥2, sensitivity and specificity were respectively 81.1% and 75.8%. TB is one of the leading causes of CAP in TB-prevalent areas. Our diagnostic index may help clinicians identify TB immediately from CAP and initiate appropriate isolation and optimal treatment.


Plasma concentrations of antipsychotic drugs in psychiatric inpatients.
In current psychiatric therapy, two or more kinds of antipsychotic drugs are usually prescribed in Japan. However, there are few data on the therapeutic plasma concentrations of antipsychotic drugs or on the correlation between the daily dose and the plasma concentration, in cases where several antipsychotic drugs had been prescribed for each patient. We measured the therapeutic plasma concentrations of 9 antipsychotic drugs in 24 psychiatric inpatients during a 6-month period. They were treated with fixed dosages of antipsychotic drugs. Plasma samples were collected early in the morning once a month, and the concentrations of antipsychotic drugs were determined by gas chromatography with nitrogen phosphorus detection, high-performance liquid chromatography (HPLC) with fluorescence detection and HPLC with UV detection. The plasma levels of chlorpromazine, levomepromazine, thioridazine, haloperidol, bromperidol, zotepine, oxypertine, sulpiride and sultopride were 21.8-92.4, 31.7-156, 101-203, 16.4-56.2, 2.72-11.7, 13.6-84.0, 29.9-80.4, 70.1-1,120 and 35.7-2,990 ng/ml, respectively. A linear correlation between the daily dose and the plasma concentration was noted for sultopride, levomepromazine, sulpiride, haloperidol, chlorpromazine and zotepine.


Blood-brain barrier carrier-mediated transport and brain metabolism of amino acids.
The transport of neutral amino acids through the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo, is an important control point for the overall regulation of cerebral metabolism, including protein synthesis and neurotransmitter production. The Michaelis-Menten kinetics of BBB amino acid transport have been investigated in vivo with the brain uptake index (BUI) technique, and in vitro with the isolated human brain capillary preparation. The only amino acid that is albumin-bound is tryptophan, and the majority of albumin-bound tryptophan in the plasma is available for transport through the BBB via an enhanced dissociation mechanism that operates at the surface of the brain capillary endothelium. The availability in brain of amino acids is predicted from the BBB Km values to be sharply influenced by supra-physiological concentrations of phenyalanine in the 200-500 microM range. Moreover, the measurement of cerebral protein synthesis with an internal carotid artery perfusion technique and HPLC-based measurements of aminoacyl-transfer RNA specific activities shows an inverse relationship between cerebral protein synthesis and plasma phenyalanine concentrations in the 200-500 microM range. These findings indicate the neurotoxicity of hyperphenylalninemia is not restricted to the phenylketonuria range of approximately 2000 microM, but is exerted in the supra-physiological range of 200-500 microM.


Effects of 'Candidatus Liberibacter solanacearum' haplotypes A and B on tomato gene expression and geotropism.
The tomato psyllid, Bactericera cockerelli Šulc (Hemiptera: Triozidae), is a pest of solanaceous crops such as tomato (Solanum lycopersicum L.) in the U.S. and vectors the disease-causing pathogen 'Candidatus Liberibacter solanacearum' (or Lso). Disease symptom severity is dependent on Lso haplotype: tomato plants infected with Lso haplotype B experience more severe symptoms and higher mortality compared to plants infected with Lso haplotype A. By characterizing the molecular differences in the tomato plant's responses to Lso haplotypes, the key components of LsoB virulence can be identified and, thus, targeted for disease mitigation strategies. To characterize the tomato plant genes putatively involved in the differential immune responses to Lso haplotypes A and B, RNA was extracted from tomato 'Moneymaker' leaves 3 weeks after psyllid infestation. Gene expression levels were compared between uninfected tomato plants (i.e., controls and plants infested with Lso-free psyllids) and infected plants (i.e., plants infested with psyllids infected with either Lso haplotype A or Lso haplotype B). Furthermore, expression levels were compared between plants infected with Lso haplotype A and plants infected with Lso haplotype B. A whole transcriptome analysis identified 578 differentially expressed genes (DEGs) between uninfected and infected plants as well as 451 DEGs between LsoA- and LsoB-infected plants. These DEGs were primarily associated with plant defense against abiotic and biotic stressors, growth/development, plant primary metabolism, transport and signaling, and transcription/translation. These gene expression changes suggested that tomato plants traded off plant growth and homeostasis for improved defense against pathogens, especially when infected with LsoB. Consistent with these results, tomato plant growth experiments determined that LsoB-infected plants were significantly stunted and had impaired negative geotropism. However, it appeared that the defense responses mounted by tomatoes were insufficient for overcoming the disease symptoms and mortality caused by LsoB infection, while these defenses could compensate for LsoA infection. The transcriptomic analysis and growth experiments demonstrated that Lso-infected tomato plants underwent gene expression changes related to abiotic and biotic stressors, impaired growth/development, impaired plant primary metabolism, impaired transport and signaling transduction, and impaired transcription/translation. Furthermore, the transcriptomic analysis also showed that LsoB-infected plants, relative to LsoA-infected, experienced more severe stunting, had improved responses to some stressors and impaired responses to others, had poorer transport and signaling transduction, and had impaired carbohydrate synthesis and photosynthesis.


Reduction in pulmonary function and increased frequency of cough associated with passive smoking in teenage athletes.
Previous studies have suggested that passive smoking (involuntary inhalation of tobacco smoke by nonsmokers) reduces small airways function. We evaluated the exposure to passive smoking and its effects on pulmonary function and symptoms in a group of 12- to 17-year-old high school athletes (N = 209; 119 boys and 90 girls) at their annual presport participation physical examinations. A structured interview was used to assess pulmonary symptoms, personal smoking habits, and passive cigarette smoke exposure. All athletes performed forced expiratory maneuvers on a portable spirometer. We measured forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow 25% to 75% (FEF25-75). The best of three FEF25-75 measured was used. Less than 70% of predicted FEF25-75 was considered abnormal. Of the 209 athletes, 7.7% were active smokers and were excluded. Of the remaining 193 athletes, 68.4% were currently exposed to passive smoking. We found a fourfold increase in incidence of low FEF25-75 and/or cough in athletes exposed to passive smoking compared with athletes not exposed: 18 of 132 exposed athletes (13.6%) had low FEF25-75 and/or cough compared with two of 61 unexposed athletes (3.3%) who had low FEF25-75 and cough (P = .02). Boys were more frequently exposed to passive smoking than girls (74% of boys [80/108] v 61% of girls [52/85] ), but the effects were more pronounced in girls. These data show a relationship between exposure to passive smoking and early pulmonary dysfunction in young athletes. The frequent exposure to passive smoke and the high prevalence of dysfunction in this population, generally considered to be healthy, is of particular concern.


Systemic Immune-Inflammation Index May Predict the Development of Contrast-Induced Nephropathy in Patients With ST-Segment Elevation Myocardial Infarction.
The aim of this study was to investigate the predictive capacity of a systemic immune-inflammation index (SII) in the detection of contrast-induced nephropathy (CIN) following ST-segment elevation myocardial infarction (STEMI). A total of 477 STEMI patients were enrolled in the study. The patients were divided into 2 groups according to CIN development. A cutoff point of 5.91 for logarithm-transformed SII was identified with 73.0% sensitivity and 57.5% specificity to predict CIN following STEMI. According to a pairwise analysis of receiver operating characteristic curve analysis, the predictive power of SII in detecting CIN following STEMI was similar to that of high-sensitivity C-reactive protein and better than the neutrophil/lymphocyte ratio or platelet/lymphocyte ratio. As a result, SII can be used as one of the independent predictors of CIN after STEMI.


Biological significance of cell cycle kinetics in 128 standard risk newly diagnosed patients with acute myelocytic leukemia.
Bromodeoxyuridine (BrdU) was administered to 128 newly diagnosed patients with standard risk acute myelocytic leukaemia (AML) for cell cycle measurements. Labelling indices (LI) were obtained from both the bone marrow aspirate (BMasp) and biopsies (bx) and durations of S-phase (Ts) and total cell cycle time (Tc) were measured by double-labelling the S-phase cells in vitro with tritiated thymidine. Median LI BMasp was 8% and from BMbx was 25%. The median Ts was 12 h (range 3.1-35 h) and Tc was 48 h (range 11.5-211 h). All patients received induction therapy with a combination of cytosine arabinoside and an anthracycline. Outcome of therapy or FAB type were not related to cell cycle characteristics. Patients with above median LI BMasp, however, had longer remission durations (P = 0.03) as did patients with above median Ts (P = 0.03) and Tc (P = 0.03). Upon longer follow-ups, even some of the patients with slowly cycling myeloblasts have relapsed (log rank P = 0.453 and 0.203 for Ts and Tc respectively). We conclude that patients with rapidly cycling cells tend to relapse faster; however, slowly cycling nature of myeloblasts is not associated with curability.


Inhibition of voltage-gated K+ channel gene expression by the neuropeptide thyrotropin-releasing hormone.
Many neurotransmitters regulate action potential activity in neuronal, endocrine, and cardiac cells by rapidly modulating the gating of K+ channels. Neurotransmitters might also produce prolonged effects on excitability by regulating the expression of K+ channel genes. Here we show that the neuropeptide thyrotropin-releasing hormone (TRH) down-regulates Kv1.5 and Kv2.1 K+ channel mRNAs in clonal pituitary cells. The effect on Kv1.5 mRNA expression does not require protein synthesis and is due to decreased transcription. Immunoblots demonstrate that Kv1.5 and Kv2.1 immunoreactivities are significantly reduced by TRH within 12 hr. The change in channel protein expression is associated with a decrease in voltage-gated K+ currents. Thus, TRH enhances excitability by inhibiting K+ channel gene expression. Neuropeptide regulation of K+ channel gene expression may produce long-term changes in neuronal action potential activity and synaptic transmission.


Mammalian Retinal Cell Quantification.
Normal retina and its cell layers are essential for processing visual stimuli, and loss of its integrity has been documented in many disease processes. The numbers and the axonal processes of retinal ganglion cells are reduced substantially in glaucoma, leading to vision loss and blindness. Similarly, selective loss of photoreceptors in age-related macular degeneration and hereditary retinal dystrophies also results in the compromise of visual acuity. Development of genetically modified mice has led to increased understanding of the pathogenesis of many retinal diseases. Similarly, in this digital era, usage of modalities to quantify the retinal cell loss has grown exponentially leading to a better understanding of the suitability of animal models to study human retinal diseases. These quantification modalities provide valuable quantifiable data in studying pathogenesis and disease progression. This review will discuss the immunohistochemical markers for various retinal cells, available automated tools to quantify retinal cells, and present an example of retinal ganglion cell quantification using HALO image analysis platform. Additionally, we briefly review retinal cell types and subtypes, salient features of retina in various laboratory animal species, and a few of the main disease processes that affect retinal cell numbers in humans.


Survival in patients with stage IV noncardia gastric cancer - the influence of DNA ploidy and Helicobacter pylori infection.
Palliative surgery followed by postoperative chemotherapy is a challenging approach in the treatment of stage IV gastric cancer yet patients must be carefully selected on the basis of likely clinical benefit. The records of 218 patients with histological diagnosis of gastric adenocarcinoma who underwent palliative surgery followed by postoperative chemotherapy were retrospectively reviewed. Twelve potential prognostic variables including tumour DNA index and serum IgG anti- Helicobacter pylori (HP) antibodies were evaluated for their influence on overall survival by multivariate analysis. The median survival was 13.25 months [95% Confidence Interval (CI) 12.00, 14.50]. Three factors were found to have an independent effect on survival: performance status (PS) [PS 60-70 vs. 90-100 Hazard Ratio (HR) 1.676; CI 1.171-2.398, p = 0.005], liver metastases (HR 1.745; CI 1.318-2.310, p < 0.001), and DNA Index as assessed by Image cytometry (2.2-3.6 vs. >3.6 HR 3.059; CI 2.185-4.283, p < 0.001 and <2.2 vs. >3.6 HR; 4.207 CI 2.751-6.433 <0.001). HP infection had no statistically significant effect on survival by either univariate or multivariate analysis. Poor pre-treatment PS, the presence of liver metastasis and high DNA Index were identified factors associated with adverse survival outcome in patients with Stage IV gastric cancer treated with palliative gastrectomy and postoperative chemotherapy. HP infection had no influence on survival of these patients.


[Immunity and physiology].
Immune system is described as a physiological system in its function and relations with the other organs (nervous, endocrine, nutritional and reproductive systems). Communications are mediated by common receptors and cytokines. Physiological reality of these interrelations has been discussed in function of stress and age.


Female and male fitness consequences of clonal growth in a dwarf bamboo population with a high degree of clonal intermingling.
Although many studies have reported that clonal growth interferes with sexual reproduction as a result of geitonogamous self-pollination and inbreeding depression, the mating costs of clonal growth are expected to be reduced when genets are spatially intermingled with others. This study examined how clonal growth affects both female and male reproductive success by studying a population of a mass-flowering plant, Sasa veitchii var. hirsuta, with a high degree of clonal intermingling. In a 10 × 10 m plot, genets were discriminated based on the multilocus genotypes of 11 nuclear microsatellite loci. The relationships between genet size and the components of reproductive success were then investigated. Male siring success and female and male selfing rates were assessed using paternity analysis. A total of 111 genets were spatially well intermingled with others. In contrast to previous studies with species forming distinct monoclonal patches, seed production linearly increased with genet size. While male siring success was a decelerating function of genet size, selfing rates were relatively low and not related to genet size. The results, in conjunction with previous studies, emphasize the role of the spatial arrangement of genets on both the quantity and quality of offpsring, and suggest that an intermingled distribution of genets can reduce the mating costs of clonal growth and enhance overall fitness, particularly female fitness.


An evaluation of memory under regional anesthesia with IV lorazepam as a premedicant.
Forty male volunteer patients undergoing regional anesthesia were evaluated for alertness and memory in a double-blind study which compared IV lorazepam (4 mg) plus IM meperidine (50 mg) with IV placebo plus IM meperidine (50 mg) as premedicants. The data indicate no significant retrograde effects. Significant differences at all measurement points from 20 minutes to 3 hours following IV drug administration indicated greater sedation and less recall and recognition of events and stimuli (auditory and visual) with the combination of lorazepam and meperidine than with placebo and meperidine. A significant number of patients over age 40 were judged to be excessively sedated after administration of lorazepam. However, respiration, blood pressure, and pulse did not appear to be differentially affected by lorazepam and there were no adverse changes even in patients considered to be oversedated.


Techniques for the identification of genes involved in psychiatric disorders.
Most psychiatric disorders are complex genetic traits involving both genetic and environmental risk factors. This paper aims to review the gene identification strategies being applied by molecular geneticists in their efforts to elucidate the genetic and molecular basis of psychiatric disorders. Future strategies will also be canvassed. The psychiatric genetic literature was reviewed to identify current strategies applied to gene identification, with examples provided where available. The future strategies and applications that will arise from genome projects, including the International Haplotype Mapping Project, are also discussed. Many advances in the techniques of gene discovery, and the increasing resources available, are rapidly being adopted by researchers and applied to the complex problem of identifying susceptibility genes for mental illnesses. Perhaps the single most important advance to date is the Human Genome Project and all that has stemmed from the vast quantity of information that this endeavour has provided. With these technological advances and the massive increase of publicly available genetic resources, several genes have recently been implicated in the susceptibility to psychiatric illnesses including schizophrenia and depression. After many years of fruitless endeavours, these recent reports indicate that the labours of researchers in psychiatric genetics are beginning to show exciting results. Identification of these susceptibility genes holds great promise, with the unravelling of the molecular and biochemical basis of some conditions now being a more realistic and tangible goal. The increasing number of genes being identified augers well for the future treatment of psychiatric disorders. The genes identified, and the pathways of genes and proteins that they implicate, will provide potential novel targets for new therapeutic drugs. Psychiatric genetics appears to be poised for significant advances in our knowledge and understanding of the molecular genetic basis of mental illness.


Genome-wide association mapping of rust resistance in Aegilops longissima.
The rust diseases, including leaf rust caused by Puccinia triticina (Pt), stem rust caused by P. graminis f. sp. tritici (Pgt), and stripe rust caused by P. striiformis f. sp. tritici (Pst), are major limiting factors in wheat production worldwide. Identification of novel sources of rust resistance genes is key to developing cultivars resistant to rapidly evolving pathogen populations. Aegilops longissima is a diploid wild grass native to the Levant and closely related to the modern bread wheat D subgenome. To explore resistance genes in the species, we evaluated a large panel of Ae. longissima for resistance to several races of Pt, Pgt, and Pst, and conducted a genome-wide association study (GWAS) to map rust resistance loci in the species. A panel of 404 Ae. longissima accessions, mostly collected from Israel, were screened for seedling-stage resistance to four races of Pt, four races of Pgt, and three races of Pst. Out of the 404 accessions screened, two were found that were resistant to all 11 races of the three rust pathogens screened. The percentage of all accessions screened that were resistant to a given rust pathogen race ranged from 18.5% to 99.7%. Genotyping-by-sequencing (GBS) was performed on 381 accessions of the Ae. longissima panel, wherein 125,343 single nucleotide polymorphisms (SNPs) were obtained after alignment to the Ae. longissima reference genome assembly and quality control filtering. Genetic diversity analysis revealed the presence of two distinct subpopulations, which followed a geographic pattern of a northern and a southern subpopulation. Association mapping was performed in the genotyped portion of the collection (n = 381) and in each subpopulation (n = 204 and 174) independently via a single-locus mixed-linear model, and two multi-locus models, FarmCPU, and BLINK. A large number (195) of markers were significantly associated with resistance to at least one of 10 rust pathogen races evaluated, nine of which are key candidate markers for further investigation due to their detection via multiple models and/or their association with resistance to more than one pathogen race. The novel resistance loci identified will provide additional diversity available for use in wheat breeding.


Nanophotonic crystals on unpolished sapphire substrates for deep-UV light-emitting diodes.
A new method has been established and employed to create a random nanophotonic crystal (NPhC) structure without photolithography on the unpolished side of a single-side-polished sapphire substrate. This nano structure has potential use in enhancing the light-extraction efficiency (LEE) of deep ultraviolet light-emitting diodes (DUV-LEDs), and has never been built for DUV-LED applications before. Two mask layers in the nano scale (Au and SiO2) were used to create the NPhC and observed using scanning electron microscopy to have an average height of 400 nm and various sizes from 10 to 200 nm. Finally, a conventional DUV-LED and a DUV-LED device with NPhC were simulated using 2D Lumerical Finite-Difference Time-Domain (FDTD) for comparison. The results show that the LEE of the DUV-LED device with this NPhC integrated was significantly directly enhanced by up to 46% and 90% for TE and TM modes, respectively, compared to the conventional DUV-LED device. Thus, this NPhC is believed to be a new, key technique to enhance the LEE of DUV-LEDs.


New phenazine based anolyte material for high voltage organic redox flow batteries.
Herein, we report the synthesis and investigation of a novel phenazine derivative M1 with oligomeric ethylene glycol ether substituents as a promising anolyte material for non-aqueous organic redox flow batteries (RFBs). The designed material undergoes a reversible and stable reduction at -1.72 V vs. Ag/AgNO3 and demonstrates excellent (>2.5 M) solubility in MeCN. A non-aqueous organic redox flow battery assembled using the novel phenazine derivative as an anolyte and a substituted triarylamine derivative as a catholyte exhibited high specific capacity (∼93% from the theoretical value), >95% Coulombic efficiency, 65% utilization of active materials and good charge-discharge cycling stability.


Health-related quality of life and disability in patients with acute unilateral peripheral vestibular disorders.
Health-related quality of life is used to denote that portion of the quality of life that is influenced by the person's health. To compare the health-related quality of life of individuals with vestibular disorders of peripheral origin by analyzing functional, emotional and physical disabilities before and after vestibular treatment. A prospective, non randomized case-controlled study was conduced in the ENT Department, between January 2015 and December 2015. All patients were submitted to customize a 36 item of health survey on quality of life, short form 36 health survey questionnaire (SF-36) and the Dizziness Handicap Inventory for assessing the disability. Individuals were diagnosed with acute unilateral vestibular peripheral disorders classified in 5 groups: vestibular neuritis, Ménière Disease, Benign Paroxysmal Positional Vertigo, cochlear-vestibular dysfunction (other than Ménière Disease), or other type of acute peripheral vertigo (as vestibular migraine). There was a statistical significant difference for each parameter of Dizziness Handicap Inventory score (the emotional, functional and physical) between the baseline and one month both in men and women, but with any statistical significant difference between 7 days and 14 days. It was found a statistical significant difference for all eight parameters of SF-36 score between the baseline and one month later both in men and women; the exception was the men mental health perception. The correlation between the Dizziness Handicap Inventory and the SF-36 scores according to diagnostics type pointed out that the Spearman's correlation coefficient was moderate correlated with the total scores of these instruments. The Dizziness Handicap Inventory and the SF-36 are useful, proved practical and valid instruments for assessing the impact of dizziness on the quality of life of patients with unilateral peripheral vestibular disorders.


Heparan sulfate proteoglycans are required for mesoderm formation in Xenopus embryos.
Mesoderm forms in the vertebrate embryo as a result of inductive interactions involving secreted growth factors and cell surface molecules. Proteoglycans have recently been implicated in the control of cell adhesion, migration and growth factor responsiveness. We have found that removal of glycosaminoglycan chains of proteoglycans from Xenopus ectodermal explants by heparinase, but not by chondroitinase, results in inhibition of elongation and mesodermal differentiation in response to signaling factors: activin, FGF and Wnt. Heparinase treatment differentially affected expression of early general and region-specific mesodermal markers, suggesting that mesodermal cell fates become specified in the early embryo via at least two signaling pathways which differ in their requirements for heparan sulfate proteoglycans. Addition of soluble heparan sulfate restored activin-mediated induction of muscle-specific actin gene in heparinase-treated explants. Finally, heparinase inhibited autonomous morphogenetic movements and mesodermal, but not neural, differentiation in dorsal marginal zone explants, which normally give rise to mesoderm in the embryo. These results directly demonstrate that heparan sulfate proteoglycans participate in gastrulation and mesoderm formation in the early embryo.


Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo.
Calorie restriction (CR) produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetylase SIRT1 has been implicated as one of the key downstream regulators of CR in yeast, rodents, and humans. Small molecule activators of SIRT1 have been identified that exhibit efficacy in animal models of diseases typically associated with aging including type 2 diabetes. To identify molecular processes induced in the liver of mice treated with two structurally distinct SIRT1 activators, SIRT501 (formulated resveratrol) and SRT1720, for three days, we utilized a systems biology approach and applied Causal Network Modeling (CNM) on gene expression data to elucidate downstream effects of SIRT1 activation. Here we demonstrate that SIRT1 activators recapitulate many of the molecular events downstream of CR in vivo, such as enhancing mitochondrial biogenesis, improving metabolic signaling pathways, and blunting pro-inflammatory pathways in mice fed a high fat, high calorie diet. CNM of gene expression data from mice treated with SRT501 or SRT1720 in combination with supporting in vitro and in vivo data demonstrates that SRT501 and SRT1720 produce a signaling profile that mirrors CR, improves glucose and insulin homeostasis, and acts via SIRT1 activation in vivo. Taken together these results are encouraging regarding the use of small molecule activators of SIRT1 for therapeutic intervention into type 2 diabetes, a strategy which is currently being investigated in multiple clinical trials.


Comparison of urinary neopterin and pseudouridine in patients with malignant proliferative diseases.
The HPLC method for the simultaneous determination of urinary neopterin, pseudouridine, and creatinine allows a rapid evaluation of the activation state of cell-mediated immunity, and the stimulation of whole-body rRNA + tRNA turnover, associated with malignant growth. Urinary neopterin and pseudouridine concentrations in healthy subjects amounted to: 106.6 +/- 34.6 mumol/mol creatinine, and 19.6 +/- 5.2 mmol/mol creatinine (mean +/- SD), respectively. The increase of neopterin excretion in patients with haematological neoplasms ranged from 146% in Hodgkin's disease to 534% in non-Hodgkin's lymphoma, whereas the increase in cancer cases ranged from 95% in adenocarcinoma of the gaster to 741% in hepatocellular carcinoma. The changes in pseudouridine excretion were much less pronounced: 63% in non-Hodgkin's lymphoma and 120% in carcinoma of the urinary bladder. The correlation coefficient between neopterin and pseudouridine was relatively low (r = 0.43), although statistically significant (P < 0.01). In the case of several neoplasms e.g. Hodgkin's disease, polycythaemia vera, and adenocarcinoma of the gaster, neopterin was significantly elevated, whereas pseudouridine remained at a normal concentration. There was a positive relationship between the stage of the disease (primary focus, regional metastases, dissemination) and urinary concentration of pseudouridine in patients with adenocarcinoma of the large intestine. In the same patients the increase of neopterin excretion was noticed both in early and advanced stages, with the highest values in disseminated disease.


The involvement of the transient receptor potential A1 (TRPA1) in the maintenance of mechanical and cold hyperalgesia in persistent inflammation.
This study investigated the role of TRPA1 in the development and maintenance of mechanical and cold hyperalgesia in persistent inflammation induced by Complete Freund's Adjuvant (CFA) in mice. The intraplantar (i.pl.) injection of CFA induced a long lasting (28 days) hyperalgesia for both mechanical and thermal (cold) stimuli. The intraperitoneal (i.p., 30-300 mg/kg), intraplantar (i.pl., 100 microg/site) or intrathecal (i.t., 10 microg/site) injection of the TRPA1 selective antagonist HC-030031 significantly reduced the mechanical hyperalgesia evaluated by the von Frey hair test. The effect of HC-030031 was evidenced on the day after CFA injection and was kept throughout the test. However, the intracerebroventricular (i.c.v., 10 microg/site) injection of HC-030031 did not interfere with CFA-induced hyperalgesia. Treatment with HC-030031 (300 mg/kg, i.p.) completely inhibited the noxious cold hyperalgesia induced by tetrafluoroethane in mice that received CFA. The pre-treatment with the TRPA1 oligonucleotide antisense (AS-ODN, i.t.) consistently prevented both mechanical and cold hyperalgesia. Interestingly, both TRPA1 protein expression and mRNA were over-expressed in spinal cord and dorsal root ganglia (DRG) of mice treated with CFA, an effect that was fully prevented by the pre-treatment with the TRPA1 antagonist HC-030031. Collectively, the present results showed that TRPA1 present at either peripheral or spinal sites play a relevant role in the development and maintenance of both mechanical and cold hyperalgesia during CFA-induced inflammation. Thus, TRPA1 selective antagonists represent promising candidates to treat hyperalgesia in persistent inflammatory states.


Mechanisms underlying chemotherapy-induced neurotoxicity and the potential for neuroprotective strategies.
Chemotherapy-induced neurotoxicity is a significant complication in the successful treatment of many cancers. Neurotoxicity may develop as a consequence of treatment with platinum analogues (cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine) and more recently, thalidomide and bortezomib. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. These symptoms may be disabling, adversely affecting activities of daily living and thereby quality of life. The incidence of chemotherapy-induced neurotoxicity appears critically related to cumulative dose and infusion duration, while individual risk factors may also influence the development and severity of neurotoxicity. Differences in structural properties between chemotherapies further contribute to variations in clinical presentation. The mechanisms underlying chemotherapy-induced neurotoxicity are diverse and include damage to neuronal cell bodies in the dorsal root ganglion and axonal toxicity via transport deficits or energy failure. More recently, axonal membrane ion channel dysfunction has been identified, including studies in patients treated with oxaliplatin which have revealed alterations in axonal Na(+) channels, suggesting that prophylactic pharmacological therapies aimed at modulating ion channel activity may prove useful in reducing neurotoxicity. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity will inevitably assist in the development of future neuroprotective strategies and in the design of novel chemotherapies with improved toxicity profiles.


A rare case of zosteriform cutaneous metastases from squamous cell carcinoma of hard palate.
A 70-year-old woman presented with painful nodules on the left side of the neck of 1 month duration. Upon questioning, the patient gave history of reverse smoking since 50 years. On examination, the patient had a superficial ulcer over the hard palate. A provisional diagnosis of zosteriform cutaneous metastases was made. Fine needle aspiration cytology of the nodule performed showed metastatic squamous cell carcinoma deposits. Later, biopsy was performed from the neck lesion and oral lesion, and it confirmed the diagnosis. Histopathology of the oral biopsy was suggestive of infiltrating squamous cell carcinoma. Biopsy of neck lesion was suggestive of squamous cell carcinoma secondaries. Majority of these cases can be misdiagnosed as herpes zoster and were treated with antiviral drugs. Distant metastases from oral squamous cell carcinoma are unusual, but generally occur in lungs, bone, and liver. Cutaneous metastasis is extremely rare, and it often reflects an advanced stage with sinister prognosis. Therefore, metastatic diseases should be considered in the differential diagnosis of zosteriform rash in the elderly.


Successful recovery of motile and viable boar sperm after vitrification with different methods (pearls and mini straws) using sucrose as a cryoprotectant.
Vitrification of sperm by direct contact with liquid nitrogen is increasing in popularity as an alternative to conventional (slow) freezing. Although slow freezing is very challenging in boar sperm cryopreservation, this is currently the standard method used. We compared vitrification in "pearls" and in "mini straws" using the in vitro fertilization media Porcine Gamete Media with 0.3 M sucrose with the standard (slow) method used to preserve boar sperm. Both vitrification methods reduced the viability of the sperm sample more than slow freezing (42.2 ± 4.3% total motility and 71.4 ± 2.3% alive), however, both protocols allowed for the successful recovery of the sperm samples. By comparing two different methods of vitrification and two different methods of post-thaw preparation we were able to determine the optimal vitrification-thaw protocol for boar sperm. When comparing pearls and mini-straws, the smaller liquid volume associated with pearls had a positive effect on the survivability of the samples, reducing sperm DNA damage (1.2 ± 0.2% vs. 5.1 ± 0.1.7%) and preserving motility (26.15 ± 2.8% vs 9.39 ± 0.9%) after thawing. In conclusion, the pearl method was the most suitable of the vitrification techniques for use with boar sperm.


A resonant sextuplet of sub-Neptunes transiting the bright star HD 110067.
Planets with radii between that of the Earth and Neptune (hereafter referred to as 'sub-Neptunes') are found in close-in orbits around more than half of all Sun-like stars1,2. However, their composition, formation and evolution remain poorly understood3. The study of multiplanetary systems offers an opportunity to investigate the outcomes of planet formation and evolution while controlling for initial conditions and environment. Those in resonance (with their orbital periods related by a ratio of small integers) are particularly valuable because they imply a system architecture practically unchanged since its birth. Here we present the observations of six transiting planets around the bright nearby star HD 110067. We find that the planets follow a chain of resonant orbits. A dynamical study of the innermost planet triplet allowed the prediction and later confirmation of the orbits of the rest of the planets in the system. The six planets are found to be sub-Neptunes with radii ranging from 1.94R⊕ to 2.85R⊕. Three of the planets have measured masses, yielding low bulk densities that suggest the presence of large hydrogen-dominated atmospheres.


Identification of an integrated stress and growth response signaling switch that directs vertebrate intestinal regeneration.
Snakes exhibit extreme intestinal regeneration following months-long fasts that involves unparalleled increases in metabolism, function, and tissue growth, but the specific molecular control of this process is unknown. Understanding the mechanisms that coordinate these regenerative phenotypes provides valuable opportunities to understand critical pathways that may control vertebrate regeneration and novel perspectives on vertebrate regenerative capacities. Here, we integrate a comprehensive set of phenotypic, transcriptomic, proteomic, and phosphoproteomic data from boa constrictors to identify the mechanisms that orchestrate shifts in metabolism, nutrient uptake, and cellular stress to direct phases of the regenerative response. We identify specific temporal patterns of metabolic, stress response, and growth pathway activation that direct regeneration and provide evidence for multiple key central regulatory molecules kinases that integrate these signals, including major conserved pathways like mTOR signaling and the unfolded protein response. Collectively, our results identify a novel switch-like role of stress responses in intestinal regeneration that forms a primary regulatory hub facilitating organ regeneration and could point to potential pathways to understand regenerative capacity in vertebrates.


Promotion of cyclic electron transport around photosystem I during the evolution of NADP-malic enzyme-type C4 photosynthesis in the genus Flaveria.
C4 plants display higher cyclic electron transport activity than C3 plants. This activity is suggested to be important for the production of ATPs required for C4 metabolism. To understand the process by which photosystem I (PSI) cyclic electron transport was promoted during C4 evolution, we conducted comparative analyses of the functionality of PSI cyclic electron transport among members of the genus Flaveria, which contains several C3, C3-C4 intermediate, C4-like and C4 species. The abundance of NDH-H, a subunit of NADH dehydrogenase-like complex, increased markedly in bundle sheath cells with the activity of the C4 cycle. By contrast, PROTON GRADIENT REGULATION5 (PGR5) and PGR5-LIKE1 increased in both mesophyll and bundle sheath cells in C4-like Flaveria palmeri and C4 species. Grana stacks were drastically reduced in bundle sheath chloroplasts of C4-like F. palmeri and C4 species; these species showed a marked increase in PSI cyclic electron transport activity. These results suggest that both the expression of proteins involved in PSI cyclic electron transport and changes in thylakoid structure contribute to the high activity of cyclic electron flow in NADP-malic enzyme-type C4 photosynthesis. We propose that these changes were important for the establishment of C4 photosynthesis from C3-C4 intermediate photosynthesis in Flaveria.


Malignant Endometrial Polyps in Uterine Serous Carcinoma: The Prognostic Value of Polyp Size and Lymphovascular Invasion.
Uterine serous carcinoma (USC) involving an endometrial polyp and concurrent extrauterine disease is associated with poor prognosis. We examined the clinicopathological profiles of patients with stage 1A USC with and without polyp involvement and the role of polyp size and lymphovascular invasion (LVI) as prognostic indicators for extrauterine disease in patients with early USC. From 2002 to 2014, 242 patients with pure USC were identified. Fisher exact test was used for categorical variables. The student t test was used for means. Logistic regression was used to compute the odds ratio for continuous and categorical variables. Among stage 1A patients, the odds ratio of developing extrauterine disease for every 1 cm increase in polyp size is 1.368 (95% confidence interval, 1.034-1.810). Polyp size is only significantly associated with advanced stage disease for patients with myometrial invasion. A higher percent of LVI was found in stage 4 patients (31%). There is no survival or recurrence difference for stage 1 patients regardless of treatment or observation. Polyp size does not predict extrauterine disease for USC patients with disease in polyp only or disease in polyp and endometrium. Further study is needed to investigate whether presence of LVI is a prognostic factor.


New insights into the evolutionary history of Fungi from a 407 Ma Blastocladiomycota fossil showing a complex hyphal thallus.
Zoosporic fungi are key saprotrophs and parasites of plants, animals and other fungi, playing important roles in ecosystems. They comprise at least three phyla, of which two, Chytridiomycota and Blastocladiomycota, developed a range of thallus morphologies including branching hyphae. Here we describe Retesporangicus lyonii gen. et sp. nov., an exceptionally well preserved fossil, which is the earliest known to produce multiple sporangia on an expanded hyphal network. To better characterize the fungus we develop a new method to render surfaces from image stacks generated by confocal laser scanning microscopy. Here, the method helps to reveal thallus structure. Comparisons with cultures of living species and character state reconstructions analysed against recent molecular phylogenies of 24 modern zoosporic fungi indicate an affinity with Blastocladiomycota. We argue that in zoosporic fungi, kinds of filaments such as hyphae, rhizoids and rhizomycelium are developmentally similar structures adapted for varied functions including nutrient absorption and anchorage. The fossil is the earliest known type to develop hyphae which likely served as a saprotrophic adaptation to patchy resource availability. Evidence from the Rhynie chert provides our earliest insights into the biology of fungi and their roles in the environment. It demonstrates that zoosporic fungi were already diverse in 407 million-year-old terrestrial ecosystems.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.


The laminar/turbulent transition in a sludge pipeline.
Globally, wastewater treatment plants are under pressure to handle high concentration sludge in a sludge treatment line. Unawareness of the non-Newtonian behaviour of the thickened sludge has the potential to cause unexpected problems when the fluid behaviour changes from turbulent to laminar flow. In this study, sludge apparent viscosity was plotted as a function of total suspended solids concentration (TSS) and shear rate. Then, the transition velocity based on several predictive models in the literature was determined. This analysis provides a practical basis for the prediction of the pipe flow behaviour of thickened sludge in troubleshooting and engineering design.


Cyclic AMP signaling and gene regulation.
Cyclic adenosine monophosphate (cAMP) is a ubiquitous second messenger produced in cells in response to hormones and nutrients. The production of cAMP is dependent upon the actions of many different proteins that affect its synthesis and degradation. An important function of cAMP is to activate the phosphorylating enzyme, protein kinase A. The key roles of cAMP and protein kinase A in the phosphorylation and regulation of enzyme substrates involved in intermediary metabolism are well known. A newly discovered role for protein kinase A is in the phosphorylation and activation of transcription factors that are critical for the control of the transcription of genes in response to elevated levels of cAMP.


Forensic Neuropathologic Phenotypes of Fungal Central Nervous System Infections: A Case Series.
Fungal infections of the central nervous system (FI-CNS) are life-threatening infections that most commonly affect immunocompromised individuals, but immunocompetent individuals may also be infected. Although FI-CNS are relatively rare, the prevalence of FI-CNS is on the rise because of the increasing number of transplant recipients, human immunodeficiency virus-infected individuals, and use of immunosuppressive therapies. Most cases of FI-CNS originate from outside the central nervous system. The etiologic fungi can be classified into 3 fungal groups: molds, dimorphic fungi, and yeasts. The clinical presentation of FI-CNS is highly variable and may be difficult to diagnose premortem. We present a case series of 3 patients, each infected by 1 representative species from each of the 3 fungal groups (Aspergillus species, Blastomyces species, Candida species) to illustrate different neuropathologic phenotypes of FI-CNS. All 3 patients had no history of immunodeficiency and were not suspected to have FI-CNS until they were diagnosed at autopsy. Fungal infections of the central nervous system are often fatal due to delayed diagnosis and diagnostic testing. Awareness of such poly-phenotypic manifestations of FI-CNS will be helpful in reducing delayed diagnosis. It is important for clinicians to include FI-CNS on the differential diagnosis when radiographic findings are nonspecific.


[Spatial distribution of American tegumentary leishmaniasis cases in Campinas, State of São Paulo, between 1992 and 2003].
This is a retrospective study with ecological features that describes the epidemiological pattern and geographical distribution of American tegumentary leishmaniasis cases in Campinas, São Paulo, between 1992 and 2003. The probable infection locations were georeferenced by means of Global Position System and spatially described using Spring 4.01 Beta software from the Brazilian National Space Research Institute. A kernel estimator was applied to identify areas of case concentration, three epidemic areas with higher case intensity were found in the municipal area in 1993/1995 and 2002/2003. Socio-demographic (gender, age, occupation, residence time), closeness of domicile to forest, and clinical form of the disease were studied. Although socio-environment characteristics of the areas were different, epidemics profiles were similar. Age, sex and occupational distribution suggest peri-domestic transmission. Proximity to forest has been a risk factor.


Treatment of myoclonus.
Myoclonus creates significant disability for patients. This symptom or sign can have many different etiologies, presentations, and pathophysiological mechanisms. A thorough evaluation for the myoclonus etiology is critical for developing a treatment strategy. The best etiological classification scheme is a modified version from that proposed by Marsden et al. in 1982. Clinical neurophysiology, as assessed by electromyography and electroencephalography, can be used to classify the pathophysiology of the myoclonus using a neurophysiology classification scheme. If the etiology of the myoclonus cannot be reversed or treated, then symptomatic treatment of the myoclonus itself may be warranted. Unfortunately, there are few controlled studies for myoclonus treatments. The treatment strategy for the myoclonus is best derived from the neurophysiology classification scheme categories: 1) cortical, 2) cortical-subcortical, 3) subcortical-nonsegmental, 4) segmental, and 5) peripheral. A cortical physiology classification is most common. Levetiracetam is suggested as first-line treatment for cortical myoclonus, but valproic acid and clonazepam are commonly used. Cortical-subcortical myoclonus is the physiology demonstrated by myoclonic seizures, such as in primary epileptic myoclonus (e.g., juvenile myoclonic epilepsy). Valproic acid has demonstrated efficacy in such epileptic syndromes with other medications providing an adjunctive role. Clonazepam is used for subcortical-nonsegmental myoclonus, but other treatments, depending on the syndrome, have been used for this physiological type of myoclonus. Segmental myoclonus is difficult to treat, but clonazepam and botulinum toxin are used. Botulinum toxin is used for focal examples of peripheral myoclonus. Myoclonus treatment is commonly not effective and/or limited by side effects.


[History of public health in the country of Vaud in the middle ages: an evaluation].
The rich archival sources of mediaeval Vaudois institutions make it possible to study a great variety of health problems of that country. Recent studies elucidate, e.g., the administration of the vineyards of the hospital of the town of Vevey as well as the management of great numbers of pilgrims or victims of a disaster by the same hospital. Progression and demographic consequences of the plaque outbreaks of 1348 and 1360 have been worked out and the network of leper-houses could be reconstructed. Finally, the ambiguous attitude of the citizens of Lausanne towards their hospital in the 14th century has been revealed: pious legacies on the one hand, endeavour to control them politically on the other.


Selection of surgical modality for massive splenomegaly in children.
Laparoscopic splenectomy (LS), a treatment for both benign and malignant splenic diseases, can prove technically challenging in patients with massive splenomegaly. In particular, the optimal surgical modality for treating massive splenomegaly in children remains controversial. The clinicopathologic data of 289 pediatric patients undergoing splenectomy for massive splenomegaly were studied in a retrospective analysis. Accordingly, the patients were classified into the LS surgery group and open splenectomy (OS) surgery group. In the laparoscopy cohort, they were separated into two subgroups according to the method of surgery: the multi-incision laparoscopic splenectomy (MILS) and the single-incision laparoscopic splenectomy (SILS) surgery groups, respectively. Patient demographics, clinical data, surgery, complications, and postoperative recovery underwent analysis. Concurrently, we compared the risk of adverse laparoscopic splenectomy outcomes utilizing univariable and multivariable logistic regression. The total operation time proved remarkably shorter in the OS group in contrast to the LS group (149.87 ± 61.44 versus 188.20 ± 52.51 min, P < 0.001). Relative to the OS group, the LS group exhibited lowered postoperative pain scores, bowel recovery time, and postoperative hospitalization time (P < 0.001). No remarkable difference existed in post-operation complications or mortality (P > 0.05). Nevertheless, the operation duration was remarkably longer in the SILS surgery group than in the MILS surgery group (200 ± 46.11 versus 171.39 ± 40.30 min, P = 0.02). Meanwhile, the operative duration of MILS and SILS displayed a remarkable positive association with splenic length. Moreover, the operative duration of SILS displayed a remarkable positive association with the age, weight, and height of the sick children. Splenic length proved an independent risk factor of adverse outcomes (P < 0.001, OR 1.378). For pediatric patients with massive splenomegaly who can tolerate prolonged anesthesia and operative procedures, LS surgery proves the optimal treatment regimen. SILS remains a novel surgery therapy which may be deemed a substitutional surgery approach for treating massive splenomegaly.


Resection with primary anastomosis vs nonrestorative resection for perforated diverticulitis with peritonitis: a systematic review and meta-analysis.
It is still controversial whether the optimal operation for perforated diverticulitis with peritonitis is primary anastomosis (PRA) or nonrestorative resection (NRR). The aim of this systematic review and meta-analysis was to evaluate mortality and morbidity rates following emergency resection for perforated diverticulitis with peritonitis and ostomy reversal, as well as ostomy nonreversal rates. The Pubmed, EMBASE, Cochrane Library, MEDLINE via Ovid, CINAHL and Web of Science databases were systematically searched. Mortality was the primary end-point. A subgroup meta-analysis of randomized controlled trials was performed in addition to a meta-analysis of all eligible studies. Odds ratios (ORs) and mean difference (MD) were calculated for dichotomous and continuous outcomes, respectively. Seventeen studies, including three randomized controlled trials (RCTs), involving 1016 patients (392 PRA vs 624 NRR) were included. Overall, mortality was significantly lower in patients with PRA compared with patients with NRR [OR (95% CI) = 0.38 (0.24, 0.60), P < 0.0001]. Organ/space surgical site infection (SSI) [OR (95% CI) = 0.25 (0.10, 0.63), P = 0.003], reoperation [OR (95% CI) = 0.48 (0.25, 0.91), P = 0.02] and ostomy nonreversal rates [OR (95% CI) = 0.27 (0.09, 0.84), P = 0.02] were significantly decreased in PRA. In the RCTs, the mortality rate did not differ [OR (95% CI) = 0.46 (0.15, 1.38), P = 0.17]. The mean operating time for PRA was significantly longer than for NRR [MD (95% CI) = 19.96 (7.40, 32.52), P = 0.002]. Organ/space SSI [OR (95% CI) = 0.28 (0.09, 0.82), P = 0.02] was lower after PRA. Ostomy nonreversal rates were lower after PRA. The difference was not statistically significant [OR (95% CI) = 0.26 (0.06, 1.11), P = 0.07]. However, it was clinically significant [number needed to treat/harm (95% CI) = 5 (3.1, 8.9)]. This meta-analysis found that organ/space SSI rates as well as ostomy nonreversal rates were decreased in PRA at the cost of prolonging the operating time.


Soft-tissue vessels and cellular preservation in Tyrannosaurus rex.
Soft tissues are preserved within hindlimb elements of Tyrannosaurus rex (Museum of the Rockies specimen 1125). Removal of the mineral phase reveals transparent, flexible, hollow blood vessels containing small round microstructures that can be expressed from the vessels into solution. Some regions of the demineralized bone matrix are highly fibrous, and the matrix possesses elasticity and resilience. Three populations of microstructures have cell-like morphology. Thus, some dinosaurian soft tissues may retain some of their original flexibility, elasticity, and resilience.


Association of Chlamydophila pneumoniae DNA in peripheral blood mononuclear cells and IgA antibody with atherosclerotic diseases.
An association has been demonstrated between Chlamydophila pneumoniae (C. pneumoniae) infection and atherosclerosis, but data on the relationship between C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) and antibodies to this organism are lacking. We investigated the C. pneumoniae DNA in PBMC by polymerase chain reaction (PCR) and C. pneumoniae IgG and IgA antibodies by enzyme-linked immunosorbent assay of 168 patients with atherosclerotic diseases and 27 controls (healthy control subjects). C. pneumoniae DNA was detected for 48/168 (29%) atherosclerosis patients, IgG for 79 (47%), and IgA for 98 (58%), whereas the corresponding numbers for the controls were 11 (41%), 13 (48%), and 7 (26%). There was no significant difference of the C. pneumoniae DNA positivity rate between the atherosclerosis patients and the controls. However, the C. pneumoniae IgA-positive rate was significantly higher for carotid atherosclerosis patients who had C. pneumoniae DNA in their PBMC than for those without it (74% vs. 18%, P < 0.05). Among the patients with coronary artery disease, the C. pneumoniae IgA antibody positive rate was significantly higher for the patients with DNA than for those without it (68% vs. 18%, P < 0.05). Our results suggest that a high C. pneumoniae IgA antibody titer and C. pneumoniae DNA positivity are associated with an increased risk of atherosclerotic diseases due to endovascular C. pneumoniae infection.


Inflammatory neuropathy in homosexual men with lymphadenopathy.
Twelve homosexual men had peripheral neuropathy with fever, night sweats, and lymphadenopathy. Sensory symptoms predominated, but there was also weakness and cranial nerve dysfunction. Manifestations were multifocal in nine and distal and symmetric in three. CSF was abnormal in all eight patients examined. Sural nerve in five patients showed axonal degeneration, accompanied in two by segmental demyelination. Four patients had epineurial and endoneurial perivascular chronic inflammatory cells without evidence of vasculitis. Neuropathy remitted spontaneously in six patients. Four patients received steroids without clinical response, although one later responded to plasmapheresis-lymphocytapheresis. Four patients later progressed to AIDS.


Mode-matching without root-finding: application to a dissipative silencer.
This article presents an analytic mode-matching approach suitable for modelling the propagation of sound in a two-dimensional, three-part, ducting system. The approach avoids the need to find roots of the characteristic equation for the middle section of the duct (the component) and is readily applicable to a broad class of problems. It is demonstrated that the system of equations, derived via analytic mode-matching, exhibits certain features which ensure that they can be recast into a form that is independent of the roots of the characteristic equation for the component. The precise details of the component are irrelevant to the procedure; it is required only that there exists an orthogonality relation, or similar, for the eigenmodes corresponding to the propagating wave forms in this region. The method is applied here to a simple problem involving acoustic transmission through a dissipative silencer of the type commonly found in heating ventilation and air-conditioning ducts. With reference to this example, the silencer transmission loss is computed, and the power balance for the silencer is investigated and is shown to be an identity that is necessarily satisfied by the system of equations, regardless of the level of truncation.


A simultaneous iris angiography technique in pigmented rabbits.
To report a simultaneous iris angiography (IA) technique combined with the use of indocyanine green (ICG) and fluorescein sodium (FS) in pigmented rabbits. 15 rabbits were randomly divided into 3 groups according to the dye doses: the dose of the lower-volume group was 2 mg FS and 2 mg ICG; the dose of the moderate-volume group was 5 mg FS and 5 mg ICG, and the dose of the higher-volume group was 8 mg FS and 8 mg ICG. Fifteen IAs were performed by a confocal scanning laser ophthalmoscope and a rapid localization technique giving a flat-on image. Simultaneous digital angiography provided two kinds of a fully dynamic video of iris vessels fluorescein in all pigmented rabbits, which is the same in pigmented and albino rabbits and no vascular pattern was hidden by the iris stromal pigment. Furthermore, dye doses influenced the IA effect in rabbits. The lower-volume dye can demonstrate iris vessels, without obvious leakage, which, however, extinguish rapidly after 10-15 s. In the higher-volume group, vascular imaging lasted longer, but subsequently significant FS and ICG leakage appeared as streams on the surface of the iris until the dye disappeared from the iris vessels; the diffuse and intense aqueous fluid lasted 1 day. The moderate-volume dye displayed vessels clearly by ICG for 300 s, without leakage; FS clear vessels were maintained for about 15-20 s and the structure of the iris became fuzzy due to quick leakage. Simultaneous IA with a rapid localization technique allows high-quality imaging of the pigmented rabbits and the moderate dosage of 5 mg FS and 5 mg ICG is preferred for best visualization.


Spontaneous reactivation in chronic hepatitis B: patterns and natural history.
We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B.


Surface and internalized Escherichia coli O157:H7 on field-grown spinach and lettuce treated with spray-contaminated irrigation water.
Numerous field studies have revealed that irrigation water can contaminate the surface of plants; however, the occurrence of pathogen internalization is unclear. This study was conducted to determine the sites of Escherichia coli O157:H7 contamination and its survival when the bacteria were applied through spray irrigation water to either field-grown spinach or lettuce. To differentiate internalized and surface populations, leaves were treated with a surface disinfectant wash before the tissue was ground for analysis of E. coli O157:H7 by direct plate count or enrichment culture. Irrigation water containing E. coli O157:H7 at 10(2), 10(4), or 10(6) CFU/ml was applied to spinach 48 and 69 days after transplantation of seedlings into fields. E. coli O157:H7 was initially detected after application on the surface of plants dosed at 10(4) CFU/ml (4 of 20 samples) and both on the surface (17 of 20 samples) and internally (5 of 20 samples) of plants dosed at 10(6) CFU/ml. Seven days postspraying, all spinach leaves tested negative for surface or internal contamination. In a subsequent study, irrigation water containing E. coli O157:H7 at 10(8) CFU/ml was sprayed onto either the abaxial (lower) or adaxial (upper) side of leaves of field-grown lettuce under sunny or shaded conditions. E. coli O157:H7 was detectable on the leaf surface 27 days postspraying, but survival was higher on leaves sprayed on the abaxial side than on leaves sprayed on the adaxial side. Internalization of E. coli O157:H7 into lettuce leaves also occurred with greater persistence in leaves sprayed on the abaxial side (up to 14 days) than in leaves sprayed on the adaxial side (2 days).


[A contribution of multidetector computed tomography to indications for chest wall stabilisation in multiple rib fractures].
Multidetector computed tomography (MDCT) is more sensitive for the detection of injury to the thoracic wall and intra-thoracic organs than a plain chest radiograph. The chest wall deformity and instability following multiple rib fracture involves fractures of four or more adjacent ribs at two levels, sometimes including a sternal fracture. It may also be associated with lung trauma (pneumothorax, haemothorax, rupture, laceration or pulmonary contussion). An isolated multiple-rib fracture can successfully be treated conservatively. Early intubation and mechanical ventilation are indicated in patients with progressive respiratory insufficiency. Indications for surgical stabilisation of this fracture are based on the signs of respiratory failure and the results of imagining methods (MDCT at the present time). Examination by MDCT was carried out in patients with severe thoracic trauma. In five patients with multiple rib fractures, the CT findings were included in indication criteria for open rib osteosynthesis and thoracotomy. A clinical indication criterion was respiratory insufficiency after the patient's weaning from a ventilator, manifested by paradoxical chest motion. A radiographic indication included an extensive chest deformity with rib displacement into the pleural cavity in 3D reconstruction from MDCT images. Surgery was performed within one hour to five days of admission. Access was gained through an oblique skin incision and by cutting though the chest wall muscles to release fractured ribs. To explore the thoracic cavity, a defect in the intercostal muscles was extended by an incision at the site of rib fracture. Suction of a haemothorax was done and lung ruptures were sutured in three patients. After chest drain insertion, the fractured ribs were stabilized by plate osteosynthesis (fy Medin). In the post-operative period, mechanical ventilation was continued for 3 to 6 days in four patients. There were no complications. In the patients with flail chest, the 3D reconstruction from MDCT images allowed us to make more exact pre- operative decisions concerning the extent of rib osteosynthesis and the method of exposure. If lung injury was also shown, this was an indication for thoracic cavity exploration. The pathophysiological effects of flail chest involve several factors including the size of a flail segment, change in intra-thoracic pressure during spontaneous breathing and multiple injuries to the intra-thoracic organs. Therapy is related to the seriousness of respiratory disorder associated with flail chest, the degree of chest wall deformity and other complications of conservative treatment (dependence on mechanical ventilation with no possibility of weaning). Surgical stabilization of the chest wall is the most reliable method of treatment which allows us to avoid or interrupt the adverse effect of rib displacement and chest instability. A contribution of MDCT examination to the indication for surgical stabilization lies in that MDCT provides imagining of the details decisive for the classification of fracture types including their tendency to displacement. MDCT permits a better visualisation of chest injury and a better understanding of the respiratory disorder. Based on 3D reconstruction from MDCT images, it is possible to make the pre-operative considerations for rib osteo- synthesis more specific and to choose the best approach. At the same time MDCT enables us to diagnose associated intra-thoracic injuries and provides indications for their treatment. In addition, it gives us a possibility to evaluate the role of a flail segment in breathing dysfunction and to establish indications for surgical stabilization in multiple rib fractures. Rib osteosynthesis allowed for early stabilization of the chest wall and improved the mechanics of breathing, thus requiring a shorter period of mechanical ventilation. The evaluation of statistical significance of these facts will be made when a larger group of patients examined by MDCT is available.


Design and test of potato seeding apparatus based on double-layer seed picking scoop structure.
At present, potato seeders in China generally have poor uniformity of seed rows and high coefficients of variation in plant spacing during seed rows, causing difficulties for subsequent mechanized plant protection and harvesting. Based on the effect of seed discharge to analyze the sowing process, a potato seed discharger with a double-layer seed picking spoon structure was designed. By analyzing the seed discharging mechanism and its operation process, the shape and size structural parameters of the seed picking spoon were determined. Finite element simulation of the seed pickup process and seed carrying process of the seed discharging mechanism was carried out by EDEM software to determine the double-layer seed scoop scheme and the range of factors for subsequent tests. A two-factor test was conducted with seeding line speed and seed drop height as test factors, and plant spacing coefficient of variation and seed potato lateral offset dispersion as test indexes. The test results showed that the double-layer seeding spoon chain seeder reduced the coefficient of variation in plant spacing by 5.8%, and the dispersion in lateral offset by 5.5 mm, compared with the single seeding spoon seeder, when the seeding speed was 0.184 m/s and the height of falling seed was 9 cm.


MUC1-specific cytotoxic T lymphocytes in cancer therapy: induction and challenge.
MUC1 glycoprotein is often found overexpressed and hypoglycosylated in tumor cells from numerous cancer types. Since its discovery MUC1 has been an attractive target for antitumor immunotherapy. Indeed, in vitro and in vivo experiments have shown T-cell-specific responses against MUC1 in an HLA-restricted and HLA-unrestricted manner, although some animal models have highlighted the possible development of tolerogenic responses against this antigen. These observations permit the development of new T-cell vaccine strategies capable of inducing an MUC1-specific cytotoxic T cell response in cancer patients. Some of these strategies are now being tested in clinical trials against different types of cancer. To date, encouraging clinical responses have been observed with some MUC1 vaccines in phase II/III clinical trials. This paper compiles knowledge regarding MUC1 as a promising tumor antigen for antitumor therapeutic vaccines applicable to numerous cancers. We also summarize the results of MUC1-vaccine-based clinical trials.


LncRNA ZNFX1-AS1 targeting miR-193a-3p/SDC1 regulates cell proliferation, migration and invasion of bladder cancer cells.
Long non-coding RNA (lncRNA) is closely associated with cancer occurrence and tumor development. However, the biological function of lncRNA ZNFX1-AS1 has not yet been reported in bladder cancer. The present study aimed to study the function of ZNFX1-AS1 in bladder cancer cells and the mechanism involved. The expression of ZNFX1-AS1 in bladder cancer tumor tissues and cell lines was examined by qRT-PCR. The effects of ZNFX1-AS1 knockdown on cell proliferation, cell cycle, cell migration, and invasion were assessed by Cell Counting Kit-8, flow cytometry (FCM), and transwell assays. Bioinformatics analyses and Luciferase reporter assays were performed to explore the mechanism by which ZNFX1-AS1 exerted its oncogenesis role in bladder cancer. The anti-tumor effect of ZNFX1-AS1 silencing on bladder cancer in vivo was also evaluated. ZNFX1-AS1 was over-expressed in bladder cancer tumor tissues and cell lines. ZNFX1-AS1 expression was found to be associated with tumor size and advanced clinical stage in patients with bladder cancer. Downregulation of ZNFX1-AS1 inhibited cell proliferation, cell clone formation, migration, and invasion of bladder cancer cells. ZNFX1-AS1 was found to interact with miR-193a-3p/Syndecan 1 (SDC1). ZNFX1-AS1 expression was negatively correlated with miR-193a-3p expression, but positively correlated with SDC1 expression in bladder cancer samples. ZNFX1-AS1 knockdown also effectively suppressed tumor growth in an in vivo xenograft model. ZNFX1-AS1 regulated bladder cancer progression by targeting the miR-193a-3p/SDC1 axis. Our study may provide novel insights for bladder cancer prognosis and therapy.


Solvent-induced transformation of single crystals of a spin-crossover (SCO) compound to single crystals with two distinct SCO centers.
The long-sought-after crystal structure of Fe(tpa)(NCS)(2) (1, tpa = tris(2-pyridylmethyl)amine), an otherwise well-studied spin-crossover (SCO) complex, has been obtained, and its one-step, incomplete spin transition was correlated to its solid-state structures at different temperatures. Upon exposure to methanol vapor, single-crystal-to-single-crystal transformation of 1 to a new SCO compound, 2, formulated as {[Fe(tpa)(NCS)(2)] x [Fe(tpa)(NCS)(2) x CH(3)OH]}, occurs with a dramatic color change from yellow to red. Crystallographic studies revealed that the asymmetric unit of the structure of 2 contains two independent Fe(II) centers. Studies by magnetic measurements and Mossbauer spectroscopy revealed a two-step complete spin transition for compound 2, between LS-LS and HS-HS, via an unambiguous intermediate LS-HS phase; the two SCO centers of disparate spin states were resolved crystallographically. That a significant portion of the original crystal structure is maintained indicates that the present approach is a more subtle means of altering the properties associated with SCO phenomenon than by changing counteranions or crystallization using different solvents. Furthermore, the dramatic changes in crystal structure and SCO behaviors triggered by mere solvent sorption suggest that this approach is rather efficient in modifying and hopefully fine-tuning and optimizing properties of SCO compounds. Coupled with the aforementioned gentleness and subtlety, the present approach of heterogeneously introducing perturbations to pre-existing supramolecular arrays of SCO units is more conducive to systematic studies aiming at the discovery of new SCO systems and phenomenon toward their ultimate materials applications.


Relevance of 4-F4t-neuroprostane and 10-F4t-neuroprostane to neurological diseases.
F4-neuroprostanes (F4-NeuroPs) are non-enzymatic oxidized products derived from docosahexaenoic acid (DHA) and are suggested to be oxidative damage biomarkers of neurological diseases. However, 128 isomers can be formed from DHA oxidation and among them, 4(RS)-4-F4t-NeuroP (4-F4t-NeuroP) and 10(RS)-10-F4t-NeuroP (10-F4t-NeuroP) are the most studied. Here, we report the identification and the clinical relevance of 4-F4t-NeuroP and 10-F4t-NeuroP in plasma of four different neurological diseases, including multiple sclerosis (MS), autism spectrum disorders (ASD), Rett syndrome (RTT), and Down syndrome (DS). The identification and the optimization of the method were carried out by gas chromatography/negative-ion chemical ionization tandem mass spectrometry (GC/NICI-MS/MS) using chemically synthesized 4-F4t-NeuroP and 10-F4t-NeuroP standards and in oxidized DHA liposome. Both 4-F4t-NeuroP and 10-F4t-NeuroP were detectable in all plasma samples from MS (n = 16), DS (n = 16), ASD (n = 9) and RTT (n = 20) patients. While plasma 10-F4t-NeuroP content was significantly higher in patients of all diseases as compared to age and gender matched healthy control subjects (n = 61), 4-F4t-NeuroP levels were significantly higher in MS and RTT as compared to healthy controls. Significant positive relationships were observed between relative disease severity and 4-F4t-NeuroP levels (r = 0.469, P <0.0001), and 10-F4t-NeuroP levels (r = 0.757, P < 0.0001). The study showed that the plasma amount ratio of 10-F4t-NeuroP to 4-F4t-NeuroP and the plasma amount as individual isomer can be used to discriminate between different brain diseases. Overall, by comparing the different types of disease, our plasma data indicates that 4-F4t-NeuroP and 10-F4t -NeuroP: i) are biologically synthesized in vivo and circulated, ii) are related to clinical severity of neurological diseases, iii) are useful to identify shared pathogenetic pathways in distinct brain diseases, and iv) appears to be distinctive for different neurological conditions, thus representing potentially new biological disease markers. Our data strongly suggest that in vivo DHA oxidation follows preferential chemical rearrangements according to different brain diseases.


Femoral Nerve Catheters Improve Home Disposition and Pain in Hip Fracture Patients Treated With Total Hip Arthroplasty.
Opioids have been the mainstay of treatment in the physiologically young geriatric hip fracture patient undergoing total hip arthroplasty (THA). However opioid-related side effects increase morbidity. Regional anesthesia may provide better analgesia, while decreasing opioid-related side effects. The goal of this study was to examine the effect of perioperative continuous femoral nerve blockade with regards to pain scores, opioid-related side effects and posthospital disposition in hip fracture patients undergoing THA. Twenty-nine consecutive geriatric hip fracture patients (22 women/7 men) underwent THA. Average follow-up was 8.3 months (6 weeks-39 months). Fifteen patients were treated with standard analgesia (SA). Fourteen patients received an ultrasound-guided insertion of a femoral nerve catheter after radiographic confirmation of a hip fracture. All complications and readmissions that occurred within 6 weeks of surgery were noted. Continuous femoral nerve catheter (CFNC) patients were discharged home more frequently than SA patients (43% for CFNC vs 7% for SA; P = .023). CFNC patients reported lower average pain scores preoperatively (P < .0001), on postoperative day 1 (P = .005) and postoperative day 2 (P = .037). Preoperatively, CFNC patients required 61% less morphine equivalent (P = .007). CFNC patients had a lower rate of opioid-related side effects compared with SA patients (7% vs 47%; P = .035). CFNC patients were discharged to home more frequently. Use of a CFNC decreased daily average patient-reported pain scores, preoperative opioid usage, and opioid-related side effects after THA for hip fracture. Based on these data, we recommend routine use of perioperative CFNC in hip fracture patients undergoing THA.


Prevalence and predictors of anemia in a population-based study of octogenarians and centenarians in Georgia.
Anemia has been associated with increased physical and financial costs and occurs more frequently in older individuals. Therefore, the primary objectives of this study were to examine the prevalence and possible predictors of anemia in the very old. Hemoglobin was used to identify those with anemia in a group of centenarians and near centenarians (98+, n = 185) and octogenarians (n = 69), who were recruited as part of the population-based multidisciplinary Georgia Centenarian Study. Blood markers, including ferritin, vitamin B12, red blood cell folate, methylmalonic acid, creatinine, and C-reactive protein, demographic variables, and medication and/or supplement usage were used to determine possible predictors of anemia. The prevalence of anemia was 26.2% in octogenarians and 52.1% in centenarians. Low serum albumin (<3.6 g/dL) and decreased estimated glomerular filtration rate (<45 mL/min/m(2)) were predictors of anemia in centenarians. Anemia is a major health issue, particularly as people age. Because of the high prevalence of anemia in older individuals, awareness of the predictors associated with anemia becomes increasingly important so as to reduce the negative consequences associated with it and allow for the identification of steps that can be taken to correct anemia, including managing chronic disease.