Interaction between ω-6 fatty acids intake and blood cadmium on the risk of low cognitive performance in older adults from National Health and Nutrition Examination Survey (NHANES) 2011-2014.
Identifying preventable diets and environmental exposure is essential to ensuring the health of the aging population. This study evaluated the interaction effect between blood cadmium and ω-6 fatty acids intake on low cognitive performance in Americans. The data of this cross-sectional study were obtained from the 2011-2012 and 2013-2014 National Health and Nutritional Examination Survey (NHANES). Cognitive performance was measured by the Consortium to Establish a Registry for Alzheimer's Disease test, Animal Fluency Test, and Digit Symbol Substitution Test. Multivariate logistic regression models were used. A total of 1,918 individuals were included, with 467 (24.35%) low cognitive performance. Compared with participants with normal-level blood cadmium, those with high-level blood cadmium had a higher risk of low cognitive performance [odds ratio (OR) was 1.558 with 95% confidence interval (CI): 1.144-2.123]. Low-level ω-6 fatty acids intake was positively associated with low cognitive performance [OR = 1.633 (95%CI: 1.094-2.436)] compared with normal-level intake. Moreover, there was a significant interaction between low-level ω-6 fatty acids intake and high-level blood cadmium on the risk of low cognitive performance (relative excess risk due to interaction: 0.570, 95%CI: 0.208-0.932; the attributable proportion of interaction: 0.219, 95%CI: 0.102-0.336; synergy index: 1.552, 95%CI: 1.189-2.027). There was a synergistic interaction between low-level ω-6 fatty acids intake and high-level blood cadmium on low cognitive performance. Low-level ω-6 fatty acids intake may amplify the adverse effects of long-term exposure to cadmium on cognitive performance. This may have a certain significance for the prevention of cognitive decline in the elderly.


Embedding iliac bone biopsies at low temperature using glycol and methyl methacrylates.
A mixture of pure and anhydrous glycol methacrylate and methyl methacrylate is used as an embedding medium for iliac bone biopsies. Infiltration is carried out at -20 C with the embedding medium and a cold inactivated catalyst-initiator system. Raising the temperature to 4 C initiates polymerization and limits the peak temperature of polymerization to 25 C. In this way, such thermolabile enzymes as osteoclastic acid phosphatase are preserved. After staining, sections are dehydrated in polyethylene glycol 400 30% in 2-propanol. This gives flat sections and improves staining properties.


Avoidance learning as predictor of posttraumatic stress in firefighters.
Avoidance is a well-established maintenance factor in anxiety-related psychopathology. Individuals prone to anxiety show more maladaptive avoidance responses in conditioning paradigms aimed at avoidance learning, which indicates impairments in safety learning. To what extent avoidance learning is associated with posttraumatic stress disorder (PTSD) is still unclear, despite the logical relevance to the symptomatology. In this prospective study, we investigate avoidance learning responses in first responders, a population at high risk for traumatic exposure and thus PTSD development, and studied whether avoidance learning was associated with concurrent and future PTSD symptoms. Firefighters (N = 502) performed an avoidance learning task at baseline assessment in which they first learned that two conditioned stimuli (CS+) were followed by an aversive stimulus (US) and one conditioned stimulus (CS-) was not. After that, they could learn to which CS avoidance of the US was effective, ineffective or unnecessary. Self-reported PTSD symptoms were assessed at baseline, and at 6, 12, 18 and 24 months. Participants exhibited comparable avoidance patterns to low anxiety individuals from previous studies. Avoidance learning responses were not associated with PTSD symptoms at baseline nor at follow-up. Our study found no evidence that avoidance learning was related to PTSD symptom severity in a high-risk, yet low symptomatic population, nor did it predict the development of PTSD symptoms at a later point in time. Future research should focus on studying avoidance learning in a clinical or high symptomatic sample to further clarify the role of avoidance learning in PTSD development.


Are diabetes guidelines truly evidence based?
The global epidemic of obesity and diabetes underscores the urgency to develop strategies to prevent cardiovascular (CV) disease in this vulnerable population. Clinical guidelines are intended to help the clinician manage these patients, but guidelines are often discordant among professional organizations and not always evidence based. Clinicians must rely upon the best available evidence, and therefore we critically reviewed the evidence behind the American Diabetes Association (ADA) 2016 guidelines on the prevention of CV disease in diabetes. We believe the most robust evidence comes from randomized controlled trials specifically designed for diabetes with hard clinical endpoints such as mortality and CV events. Our analysis supports the ADA recommendations regarding a Mediterranean diet, glycemic control, and BP control, but we believe the evidence to support aspirin and statin therapy in diabetes is inconclusive. This discordance may be multi-factorial including the exclusion of some relevant studies and an over-reliance upon subgroup and meta-analysis. Given the lack of mortality benefit and inconsistent clinical benefits of aspirin and statins, it is essential that clinicians individualize treatment decisions while carefully weighing the risks and harms of any intervention.


Stimulation of gonadotropin release and of ovarian development, by the administration of a gonadoliberin agonist and of dopamine antagonists, in female silver eel pretreated with estradiol.
In freshwater or seawater female silver eel, the release of gonadotropin (GTH) accumulated in the pituitary under estradiol (E2) influence could be stimulated by a conjugated treatment with a mammalian gonadoliberin agonist (GnRH-A = des-Gly10, (D-Ala6)-LH-RH ethylamide) and a blocker of dopamine receptor (pimozide). Furthermore, despite the GTH release, no reduction or even a significant increase in pituitary GTH levels were noted, indicating a stimulation of GTH synthesis. In consequence of the endogenous GTH release, a stimulation of ovarian development was induced, as demonstrated by the gonadosomatic index and histological study. Similar results were obtained with a combined treatment with GnRH-A and an inhibitor of catecholamine synthesis (L-alpha-methyl-3,4-dihydroxyphenylalanine). In contrast, no effect was produced by GnRH-A, pimozide, or L-alpha-methyl-DOPA, given alone. The results suggest that a double neuroendocrine mechanism (a lack of GnRH production and a dopaminergic inhibition of GnRH action) is involved in the prepubertal blockage of eel gonadotropic function before the reproductive migration.


A photodynamically sensitized dendritic cell vaccine that promotes the anti-tumor effects of anti-PD-L1 monoclonal antibody in a murine model of head and neck squamous cell carcinoma.
Immune checkpoint inhibitors are promising tools in combating several cancers, including head and neck squamous cell carcinoma (HNSCC). However, a substantial portion of HNSCC patients do not respond to PD-L1 antibody. Here we describe a photodynamic therapeutic (PDT) approach to enhance anti-tumor effects of the anti-PD-L1 antibody. Phototoxicity of PDT was confirmed using fluorescence microscopy, Cell Counting Kit-8 (CCK-8), Enzyme Linked Immunosorbent Assay (ELISA) and flow cytometry analyses. Phenotypic and functional maturation of immature DCs (imDCs) induced by PDT were measured using flow cytometry and ELISA. A mouse model was established using the HNSCC line, SCC7, and was used to evaluate therapeutic effects of PDT-DC vaccine in facilitating anti-tumor immunity of PD-L1 antibody. Immunogenic cell death (ICD) of SCC7 cells was induced by PDT with 0.5 µM of m-THPC and the 5 J/cm2 of light dose. ICD of SCC7 cells stimulated imDCs maturation. In vivo assays suggested that PDT-DC vaccine and anti-PD-L1 mAb synergistically induced anti-tumor immunity and suppressed tumor progression. PDT-DC vaccine enhances therapeutic effects of PD-L1 antibody, which might provide a novel approach for HNSCC immunotherapy.


Using Protein-Fragment Complementation Assays (PCA) and Peptide Arrays to Study Telomeric Protein-Protein Interactions.
Studying protein-protein interactions is critical to our understanding of signaling pathways. Telomere Interactome is assembled around telomeres and consists of proteins and factors from diverse pathways. Dissecting how this protein network contributes to telomere protection and length regulation requires the elucidation of the complex and dynamic interactions between the proteins within the interactome. Here, we focus on three assays, Bi-molecular Fluorescence Complementation (BiFC), Gaussia Luciferase Protein-fragment Complementation Assay (GLuc PCA), and OPAL peptide array, which have proven vital in our studies of telomere protein interaction networks.


Creatine kinase BB isoenzyme levels by radioimmunoassay in patients with neurological disease.
Creatine kinase BB (CK-BB) isoenzyme was measured by radioimmunoassay in serum and in cerebrospinal fluid from 61 patients with various neurological disorders. Statistically significant elevations of CK-BB isoenzyme in the serum were observed in patients with acute cerebrovascular accidents and in those with seizures and a prolonged alteration in level of consciousness. Statistically significant elevations of CK-BB isoenzyme in the cerebrospinal fluid were also found in patients who had suffered acute cerebrovascular accidents. Some patients with central nervous system infections, acute demyelinating disease, certain drug overdoses, head trauma, and complex migraine also had elevations of serum and CSF CK-BB isoenzyme. In 2 patients with elevations of CK-BB isoenzyme, the elevations in serum occurred later than those detected in the cerebrospinal fluid. If CK-BB elevations determined by radioimmunoassay can be demonstrated to be quantitatively related to the extent of brain damage, then these determinations in conjunction with experimental animal models and newer radiological techniques should allow evaluation, in an objective and precise manner, of measures designed to decrease that damage.


S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin.
Ovarian cancer is the leading cause of gynecological cancer-related mortality. The novel oncogene S100A10 has been reported to be involved in cancer cell proliferation, invasion and metastasis. The role of S100A10 in ovarian cancer has not been well studied and the effect of S100A10 on chemotherapy remains unclear. The aims of the present study were to investigate the functional role of S100A10 in the progression and carboplatin sensitivity of ovarian cancer. We examined the expression levels in tissues of S100A10 in 138 cases of ovarian cancer by IHC. To determine the functional roles of downregulated S100A10 in ovarian cancer, cell proliferation, colony formation, cell migration and invasion assays were performed. Chemoresistance was analyzed by apoptosis assay. A xenograft tumor model was established to confirm the role of S100A10 in carboplatin resistance in vivo. Using Western blot assays, we also explored the possible mechanisms of S100A10 in ovarian cancer. The results showed that increased expression of S100A10 was positively associated with carboplatin resistance (P < 0.001), tumor grade (P = 0.048) and a poorer prognosis (P = 0.0053). Functional analyses demonstrated that S100A10 suppression significantly suppressed ovarian cancer cell proliferation, colony formation, cell migration and invasion, remarkably increased carboplatin-induced apoptosis in SKOV3 and A2780 cells and inhibited tumor growth in vivo. Downregulation of S100A10 expression could inhibit cell proliferation and enhance ovarian cancer cell sensitivity to carboplatin, possibly involving the regulation of cleaved-Caspase3 and cleaved-PARP. Together, the results of the present study reveal that S100A10 expression can be used as a predictive marker for the prognosis of ovarian cancer and chemosensitivity to carboplatin.


Therapeutic applications of repetitive transcranial magnetic stimulation (rTMS) in movement disorders: a review.
Repetitive transcranial magnetic stimulation (rTMS) is emerging as a valuable adjunctive therapeutic modality in movement disorders. It is a non-invasive technique of repeated stimulation of the cerebral cortex by a train of magnetic pulses. The therapeutic effect of rTMS was first noted in depression. Later several researchers have investigated the role of rTMS in various movement disorders, notably Parkinson's disease, dystonia, Tourette's syndrome etc. The rTMS protocols used in these studies vary widely, lacks uniformity and often the results are not consistent. The optimal rTMS parameters for each disorder are yet to be established. This review discusses the current knowledge on the therapeutic applications of rTMS in various movement disorders.


Exercise therapy and other types of physical therapy for patients with neuromuscular diseases: a systematic review.
To summarize and critically appraise the available evidence on exercise therapy and other types of physical therapies for patients with neuromuscular diseases (NMD). Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews, Medline, CINAHL, EMBASE (Rehabilitation and Physical Medicine), and reference lists of reviews and articles. Randomized clinical trials (RCTs), controlled clinical trials (CCTs), and other designs were included. Study participants had to have any of the following types of NMD: motoneuron diseases, disorders of the motor nerve roots or peripheral nerves, neuromuscular transmission disorders, or muscle diseases. All types of exercise therapy and other physical therapy modalities were included. Outcome measures had to be at the level of body functions, activities, or participation according to the definitions of the International Classification of Functioning, Disability and Health (ICF). Two reviewers independently decided on inclusion or exclusion of articles and rated the methodologic quality of the studies included. All RCTs, CCTs, and other designs only if of sufficient methodologic quality were included in a best evidence synthesis. A level of evidence was attributed for each subgroup of NMD and each type of intervention. Initially 58 studies were included: 12 RCTs, 5 CCTs, and 41 other designs. After methodologic assessment, 19 other designs were excluded from further analysis. There is level II evidence ("likely to be effective") for strengthening exercises in combination with aerobic exercises for patients with muscle disorders. Level III evidence ("indications of effectiveness") was found for aerobic exercises in patients with muscle disorders and for the combination of muscle strengthening and aerobic exercises in a heterogeneous group of muscle disorders. Finally, there is level III evidence for breathing exercises for patients with myasthenia gravis and for patients with myotonic muscular dystrophy. Adverse effects of exercise therapy were negligible. The available evidence is limited, but relevant for clinicians. Future studies should be preferably multicentered, and use an international classification of the variables of exercise therapy and an ICF core set for NMD in order to improve comparability of results.


Hippocampal dendritic spines express the RyR3 but not the RyR2 ryanodine receptor isoform.
The hippocampus is a brain region implicated in synaptic plasticity and memory formation; both processes require neuronal Ca2+ signals generated by Ca2+ entry via plasma membrane Ca2+ channels and Ca2+ release from the endoplasmic reticulum (ER). Through Ca2+-induced Ca2+ release, the ER-resident ryanodine receptor (RyR) Ca2+ channels amplify and propagate Ca2+ entry signals, leading to activation of cytoplasmic and nuclear Ca2+-dependent signaling pathways required for synaptic plasticity and memory processes. Earlier reports have shown that mice and rat hippocampus expresses mainly the RyR2 isoform, with lower expression levels of the RyR3 isoform and almost undetectable levels of the RyR1 isoform; both the RyR2 and RyR3 isoforms have central roles in synaptic plasticity and hippocampal-dependent memory processes. Here, we describe that dendritic spines of rat primary hippocampal neurons express the RyR3 channel isoform, which is also expressed in the neuronal body and neurites. In contrast, the RyR2 isoform, which is widely expressed in the neuronal body and neurites of primary hippocampal neurons, is absent from the dendritic spines. We propose that this asymmetric distribution is of relevance for hippocampal neuronal function. We suggest that the RyR3 isoform amplifies activity-generated Ca2+ entry signals at postsynaptic dendritic spines, from where they propagate to the dendrite and activate primarily RyR2-mediated Ca2+ release, leading to Ca2+ signal propagation into the soma and the nucleus where they activate the expression of genes that mediate synaptic plasticity and memory.


Two different effects of calcium on aquaporins in salinity-stressed pepper plants.
Two different effects of calcium were studied, respectively, in plasma membrane vesicles and in protoplasts isolated from roots of control pepper plants (Capsicum annuum L cv. California) or of plants treated with 50 mM NaCl, 10 mM CaCl(2) or 10 mM CaCl(2) + 50 mM NaCl. Under saline conditions, osmotic water permeability (P ( f )) values decreased in protoplasts and plasma membrane vesicles, and the same reduction was observed in the PIP1 aquaporin abundance, indicating inhibitory effects of NaCl on aquaporin functionality and protein abundance. The cytosolic Ca(2+) concentration, [Ca(2+)](cyt), was reduced by salinity, as observed by confocal microscope analysis. Two different actions of Ca(2+) were observed. On the one hand, increase in free cytosolic calcium concentrations associated with stress perception may lead to aquaporin closure. On the other hand, when critical requirements of Ca(2+) were reduced (by salinity), and extra-calcium would lead to an upregulation of aquaporins, indicating that a positive role of calcium at whole plant level combined with an inhibitory mechanism at aquaporin level may work in the regulation of pepper root water transport under salt stress. However, a link between these observations and other cell signalling in relation to water channel gating remains to be established.


Updates on the APBI-IMRT-Florence Trial (NCT02104895) Technique: From the Intensity Modulated Radiation Therapy Trial to the Volumetric Modulated Arc Therapy Clinical Practice.
Several phase 3 trials have demonstrated partial breast irradiation noninferiority compared with whole breast irradiation in terms of local control and similar or reduced toxicity. During recent years, especially owing to the COVID-19 pandemic, a growing interest in 5-fraction regimens emerged. The APBI-IMRT-Florence trial (NCT02104895) schedule (30 Gy in 5 fractions) might represent an appealing treatment option, being both a safe and effective partial breast irradiation schedule, with long-term reported results. The aim of this report is to support planners interested in implementing this technique and to warrant equal access to postoperative radiation treatment for most early breast cancer patient candidates. We report the current delivery technique optimized from the original protocol and the updated dose constraints for plan optimization. We also report a statistical analysis of dosimetric parameters on 50 patients treated in consecutive fractions. Treatment-related toxic effects were assessed using the acute radiation morbidity scoring criteria and late radiation morbidity scoring scheme from the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer. The mean volume of ipsilateral breast was 731 cm3 (standard deviation ± 450; range, 151-2205) and the mean planning target volume (PTV) was 139 cm3 (standard deviation ± 48; range, 55-259). There was good correlation between ipsilateral breast V15Gy and the ratio between the PTV and ipsilateral breast volume (R2 = .911). At a median follow-up of 4.5 years, 32% of patients (n = 16) developed any grade 1 acute toxic effect. No grade >1 toxic effect was observed. Sixteen percent of patients (n = 8) developed any grade 1 late toxic effect. No grade >1 toxic effect was observed. Physician-assessed cosmesis was reported as excellent (84%), good (14%), and fair (2%). The schedule of 30 Gy in 5 consecutive fractions might represent a safe, easy-to-deliver, and cost-effective option for appropriately selected patients affected by early breast cancer.


Characterization of the sources and health risks of polycyclic aromatic hydrocarbons in PM2.5 and their relationship with black carbon: A case study in northern Taiwan.
Polycyclic aromatic hydrocarbons (PAHs) and black carbon (BC) often coexist in PM2.5 because both form during the incomplete combustion of organic matter. These compounds are regarded as hazardous air pollutants with potential health effects, including respiratory and cardiovascular effects. In this study, to evaluate the health risks of PAHs and BC at an urban site in northern Taiwan, 16 priority PAHs and BC, identified by the United States Environmental Protection Agency, were analyzed and quantified in PM2.5 to determine their concentrations, their relationship with each other, and their likely sources. The results indicated that the mean concentrations of total PAHs and BC were 0.91 ng m-3 and 0.97 μg m-3, respectively, with a significant positive correlation between them, indicating the same emission sources. The results also indicated that fossil fuel combustion and traffic emissions were primary contributors to PAHs, with wood and biomass combustion playing a less prominent role. Among these 16 priority PAHs, benzo[a]pyrene, dibenz[a,h]anthracene, benzo[b]fluoranthene, and indeno[1,2,3-cd]pyrene served as major carcinogenic compounds, accounting for 89.0% of the total carcinogenic toxicity. Thus, the lifetime excess cancer risk resulting from PAH exposure was estimated as 8.03 × 10-6, indicating a potential carcinogenic risk to human health at the sampling site. Overall, this study highlights the need for future mitigation policies for traffic emissions and fossil fuel combustion for reducing the local emissions of BC and co-produced PAHs in northern Taiwan.


Serum NOX1 and Raftlin as new potential biomarkers of Major Depressive Disorder: A study in treatment-naive first episode patients.
Biological factors are known to be important in understanding the pathogenesis of Major Depressive Disorder (MDD). Oxidative stress and neuroinflammation pathways are likely to play a critical role here. We undertook a study to investigate two novel biomarkers - serum NADPH oxidase 1 (NOX1) and Raftlin levels - in treatment-naive, smoking-free first episode patients with MDD compared to healthy controls (HCs) matched for age, sex and body mass index. We found increased NOX1 and Raftlin levels in MDD patients compared to HCs. Both parameters showed very good diagnostic performance in the MDD group. In addition, we found a significant positive correlation between depression severity (HAMD) scores and both biomarker levels in the patient group. To the best of our knowledge, this is the first human study to evaluate serum NOX1 and Raftlin levels in depression. NOX1, an important source of reactive oxygen species (ROS), and Raftlin, which may play a role in the inflammatory process, represent novel potential biomarkers of MDD. These findings support the implication of oxidative stress and inflammatory processes in patients with MDD, and indicate that the deteriorated ROS-antioxidant balance can be regulated via NOX1 in patients with depression.


Phosphodiesterase 7 inhibition induces dopaminergic neurogenesis in hemiparkinsonian rats.
Parkinson's disease is characterized by a loss of dopaminergic neurons in a specific brain region, the ventral midbrain. Parkinson's disease is diagnosed when approximately 50% of the dopaminergic neurons of the substantia nigra pars compacta (SNpc) have degenerated and the others are already affected by the disease. Thus, it is conceivable that all therapeutic strategies, aimed at neuroprotection, start too late. Therefore, an urgent medical need exists to discover new pharmacological targets and novel drugs with disease-modifying properties. In this regard, modulation of endogenous adult neurogenesis toward a dopaminergic phenotype might provide a new strategy to target Parkinson's disease by partially ameliorating the dopaminergic cell loss that occurs in this disorder. We have previously shown that a phosphodiesterase 7 (PDE7) inhibitor, S14, exerts potent neuroprotective and anti-inflammatory effects in different rodent models of Parkinson's disease, indicating that this compound could represent a novel therapeutic agent to stop the dopaminergic cell loss that occurs during the progression of the disease. In this report we show that, in addition to its neuroprotective effect, the PDE7 inhibitor S14 is also able to induce endogenous neuroregenerative processes toward a dopaminergic phenotype. We describe a population of actively dividing cells that give rise to new neurons in the SNpc of hemiparkinsonian rats after treatment with S14. In conclusion, our data identify S14 as a novel regulator of dopaminergic neuron generation. Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the ventral midbrain. Currently, no cure and no effective disease-modifying therapy are available for Parkinson's disease; therefore, an urgent medical need exists to discover new pharmacological targets and novel drugs for the treatment of this disorder. The present study reports that an inhibitor of the enzyme phosphodiesterase 7 (S14) induces proliferation in vitro and in vivo of neural stem cells, promoting its differentiation toward a dopaminergic phenotype and therefore enhancing dopaminergic neuron generation. Because this drug is also able to confer neuroprotection of these cells in animal models of Parkinson's disease, S14 holds great promise as a therapeutic new strategy for this disorder.


Knee MRI biomarkers associated with structural, functional and symptomatic changes at least a year from ACL injury - A systematic review.
Osteoarthritis (OA) results from various aetiologies, including joint morphology, biomechanics, inflammation, and injury. The latter is implicated in post-traumatic OA, which offers a paradigm to identify potential biomarkers enabling early identification and intervention. This review aims to describe imaging features associated with structural changes or symptoms at least one year following injury. A systematic review was conducted using PRISMA guidance, prospectively registered on PROSPERO (CRD42022371838). Three independent reviewers screened titles and abstracts, followed by full-texts, performed data extraction, and risk of bias assessments (Newcastle-Ottawa Scale). Inclusion criteria included imaging studies involving human participants aged 18-45 who had sustained a significant knee injury at least a year previously. A narrative synthesis was performed using synthesis without meta-analysis methodology. Six electronic databases and conference proceedings were searched, identifying 11 studies involving 776 participants. All studies included participants suffering an anterior cruciate ligament (ACL) injury and utilised MRI. Different, and not directly comparable, techniques were used. MRI features could be broadly divided into structural, including joint position and morphology, and compositional. Promising biomarkers for diagnosing and predicting osteoarthritis include T1rho and T2 relaxation time techniques, bone morphology changes and radiomic modelling. As early as 12 months after injury, differences in tibia position, bone morphology, presence of effusion and synovitis, and cartilage/subchondral bone composition can be detected, some of which are linked with worse patient-reported or radiological progression. Standardisation, including MR strength, position, sequence, scoring and comparators, is required to utilise clinical and research OA imaging biomarkers fully.


Activation of c-Ki-ras coexists with c-myc amplification in cells from a nude mouse tumor induced by the human breast carcinoma cell line SW 613-S.
In vitro transfection experiments have shown that cooperation between two different oncogenes can confer a fully malignant phenotype to primary rodent cells. We have previously reported that SW 613-Tul cells, derived from a tumor induced in a nude mouse by the human breast carcinoma cell line SW 613-S, showed a 30-fold amplification of the c-myc gene. In the present work, we show that these cells also harbor an activated c-Ki-ras gene capable of inducing the formation of foci upon transfection of NIH 3T3 cells with SW 613-Tul genomic DNA. Our results suggest that both the c-myc and c-Ki-ras oncogenes, activated by two different mechanisms, may cooperate in the full expression of the tumorigenic phenotype of SW 613-Tul cells.


Obstructive Ileus caused by blood clot after emergency total gastrectomy in a patient with hemophilia A: report of a case.
We report herein the extremely unusual case of a patient with hemophilia A who developed a hematoma ileus soon after undergoing an emergency total gastrectomy. Postoperatively, the patient was found to have an obstruction in the small intestine that was difficult to differentiate from intussusception. Reoperation revealed the cause of the obstruction to be a large blood clot. This case report serves to demonstrate that careful hemostasis and observation during surgery is essential in patients with hemophilia.


Guanine-guided time-resolved luminescence recognition of DNA modification and i-motif formation by a terbium(III)-platinum(II) complex.
Site-specific recognition of DNA modification or the formation of noncanonical structures has important applications in molecular biology, disease diagnosis, and gene expression analysis. In this study, we introduce a guanine-guided sensing tool using a terbium(III)-platinum(II) complex (TPC) as a time-resolved luminescence probe to site-specifically recognize DNA modification and i-motif formation in aqueous solution. The probe is composed of a TbIII center as the luminescent reporter and two PtII units as the receptor for guanine (G) nucleobase. TPC exhibits remarkable reaction selectivity for guanine nucleotides over other nucleotides, giving rise to a significant increase in luminescence. The luminescence enhancement of TPC is mainly attributed to an energy transfer from G base to the TbIII center after the specific coordination of PtII with N7 of guanine (N7-G), which would be facilitated by the phosphates through promoting the departure of coordinated water and bringing G closer to TbIIIvia noncovalent interactions. Based on such sensing feature, the enhanced luminescence of TPC sensitized by G nucleotides can correspondingly decrease upon N7-G modifications of DNA or i-motif formation through constructing simple guanine-guided sensing tools. This probe would provide a useful strategy for site-specific recognition of DNA for extensive purposes.


Responses to intravenous and oral diltiazem in elderly and younger patients with systemic hypertension.
Diltiazem concentrations and blood pressure, heart rate, PR interval and forearm vascular resistance responses to intravenous (25 and 50 mg) and oral (120 mg) diltiazem were compared in 13 elderly persons (mean age 68 +/- 4 years) and 10 young persons (mean 30 +/- 5 years) with essential hypertension. Diltiazem elimination was slower in the elderly. After a dose of 25 mg, clearance was 13 +/- 4 ml/min/kg in the elderly and 23 +/- 7 in the young (p less than 0.05); after 50 mg, 16 +/- 6 and 21 +/- 12 ml/min/kg (p less than 0.05); and after oral administration, 22 +/- 9 and 35 +/- 14 ml/kg/min (p less than 0.02). No age-related differences in volume of distribution (by model or area methods) were seen. Elimination half-lives were 4.5 +/- 2.2 hours in the elderly and 3.8 +/- 0.7 hour in the young persons (p less than 0.01); 4.5 +/- 1.6 and 3.3 +/- 0.7 hours (p = 0.10); and 4.7 +/- 1.5 and 3.3 +/- 1.8 hours (p = 0.08) after 50, 25 and 120 mg. Maximal decreases in mean blood pressure were from 113 +/- 14 to 91 +/- 12 mm Hg (19%) in the elderly patients and from 108 +/- 8 to 99 +/- 9 mm Hg in the younger patients (8%) after 50 mg; from 106 +/- 13 to 93 +/- 14 mm Hg and from 109 +/- 11 to 99 +/- 13 mm Hg, respectively, after 25 mg; and from 113 +/- 10 to 97 +/- 10 mm Hg and from 109 +/- 11 to 97 +/- 8 after 120 mg orally.(ABSTRACT TRUNCATED AT 250 WORDS)


Neuritogenesis and neuronal differentiation promoted by 2,4-dinitrophenol, a novel anti-amyloidogenic compound.
Neurite outgrowth is a critical event in neuronal development, formation, and remodeling of synapses, response to injury, and regeneration. We examined the effects of 2,4-dinitrophenol (DNP), a recently described blocker of the aggregation and neurotoxicity of the beta-amyloid peptide, on neurite elongation of central neurons. Morphometric analysis of rat embryo hippocampal and cortical neuronal cultures showed that neurite outgrowth was stimulated by DNP. This effect was accompanied by increases in the neuronal levels of the microtubule-associated protein tau and of cyclic adenosine 3',5' monophosphate (cAMP). DNP also promoted cAMP accumulation, increased tau level, neurite outgrowth, and neuronal differentiation in the mouse neuroblastoma cell line N2A. We show that DNP-induced differentiation requires activation of the extracellular signal-regulated kinase (ERK). The finding that DNP promotes neuritogenesis and neuronal differentiation suggests that, in addition to its anti-amyloidogenic actions, it may be a useful lead compound in the development of novel therapeutic approaches targeting neurite dystrophy and synaptic dysfunction in neurodegenerative pathologies such as Alzheimer's disease.


[Morphological investigations of turkey hearts after feeding ofFusarium toxins].
100 turkey poults (1 day of age) were housed in 16 boxes, each containing 6-7 animals. In each case 4 boxes constituted 4 feeding groups. One was the control group and the other three received a feed containing different quantities of the mycotoxin moniliformin (0.8; 1.6; 2.4 mg/kg) and beauvericin (0.8; 1.7; 2.5 mg/kg). The animals were fed for 12 weeks and then slaughtered. Pieces of the heart were examined by routine histology. The microscopical evaluation showed cell infiltration into the heart muscle and alterations of the heart muscle. However, a relation could be detected between the mycotoxin concentration in the feed and the frequency and the quality of heart alterations.


Stable solution of induced modulation instability.
In this paper,we discussed the nonlinear evolution of modulation instability and the steady-state process of induced modulation instability in sine-oscillatory response nonlocal nonlinear media. With plane wave plus perturbation as initial conditions, we simulated the long-term evolution of modulation instability in the nonlocal nonlinear Schrodinger equation with sine-oscillatory response numerically. For the input of modulated wave, the approximate analytical solution of the stable solution of the equation is obtained under the assumption that only the fundamental wave and the first harmonic wave are present. For the input of modulated wave with arbitrary harmonic waves, we obtained the exact numerical solution of the stable solution of the induced modulation instability.


p51/p63, a novel p53 homologue, potentiates p53 activity and is a human cancer gene therapy candidate.
p51 (p73L/p63/p40/KET), a recently isolated novel p53 homologue, binds to p53-responsive elements to upregulate some p53 target genes and has been suggested to share partially overlapping functions with p53. p51 may be a promising candidate target molecule for anti-cancer therapy. In this study, we adenovirally transduced p51A cDNA into human lung, gastric and pancreatic cancer cells and analyzed the intracellular function of p51 in anti-oncogenesis in vitro and in vivo. Overexpression of p51A revealed an anti-proliferative effect in vitro in all the cancer cells examined in this study. The anchorage-dependent and -independent cell growth of EBC1 cells carrying mutations in both p51 and p53 was suppressed and significant apoptosis following adenoviral transduction with p51 and/or p53 was seen. This growth suppression was cooperatively enhanced by the combined infection with adenoviral vectors encoding both p51 and p53. Furthermore, p51 activated several, but not all, p53-inducible genes, indicating that the mechanisms controlling p51- and p53-mediated tumor suppression differed. Our observations indicate that, although p51 exhibited reduced anti-oncogenetic effects compared with p53, it cooperatively enhanced the anti-tumor effects of p53. Our results suggest that p51 functions as a tumor suppressor in human cancer cells in vitro and in vivo and may be useful as a potential tool for cancer gene therapy.


Metabolically improved exopolysaccharide production by Streptococcus thermophilus and its influence on the rheological properties of fermented milk.
Altered levels of enzymes in the central carbon metabolism in Streptococcus thermophilus increased the exopolysaccharide (EPS) production 3.3 times over that of the parent strain. The influence of enhanced EPS production on the rheological properties of fermented milk is described for engineered strains of S. thermophilus which produce different levels of EPSs.


Post-ischemic changes of [3H]glycine binding in the gerbil brain after cerebral ischemia.
Sequential changes of [3H]glycine binding in the gerbil were investigated in selectively vulnerable areas 1 h to 7 days after 10 min of cerebral ischemia. A significant reduction in [3H]glycine binding was found in the hippocampus and thalamus from as early as 1 h after ischemia. In contrast, the striatum and frontal cortex showed a significant decline in [3H]glycine binding from 5 h after recirculation. Thereafter, a severe reduction in [3H]glycine binding was observed in all regions 7 days after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity was unaffected in the hippocampus, frontal cortex and thalamus up to 48 h after ischemia. Thereafter, a severe loss of MAP2-immunoreactive neurons was found in these regions, especially in the hippocampal CA1 sector. However, the striatum showed a severe loss of MAP2 immunoreactivity from 24 h after ischemia. These results demonstrate that transient cerebral ischemia causes severe reduction in [3H]glycine binding throughout the brain, and this reduction precedes the neuronal damage in selectively vulnerable areas. These findings suggest that a neurotransmitter, glycine, may play a key role in the pathogenesis of post-ischemic neurodegeneration in selectively vulnerable areas.


Marital quality and depression as mediators linking childhood maltreatment to adult physical health.
Childhood maltreatment is known to influence adult physical health among midlife adults. Evidence suggests that depressive symptoms mediate the association. However, research has discounted the role of marital quality in understanding health outcomes among adults maltreated in childhood. To advance this line of inquiry, we examined the relationship between marital quality and depressive symptoms in a sequential mediation model linking childhood maltreatment to adult physical health over ten years. Our sample consisted of midlife adults (n = 550) from three waves of the Midlife Development in the United States (MIDUS) study. The majority (n = 91.4 %) were white. At MIDUS 2, the mean age was 54.84 (SD = 10.78) and the mean age at MIDUS 3 was 63.96 (SD = 10.81). Structural equation modeling was used to examine the degree to which marital quality and depressive symptoms mediated the relationship between childhood maltreatment and adult physical outcomes. Bootstrapping procedures were used to estimate the indirect effects. The serial mediation effects from maltreatment to adult physical health through marital quality and depressive symptoms were significant. Likewise, the simple indirect effects from maltreatment to subjective evaluations and the number of chronic health conditions through depressive symptoms were also significant. Childhood maltreatment is linked to adult physical health problems through marital quality and depressive symptoms, suggesting that the quality of adult marriages may play a critical role in health outcomes. Improving the quality of marriages may reduce risk factors, such as depression, that potentate future physical health problems.


Using a cartoon questionnaire to improve consent process in children: a randomized controlled survey.
The aim of the study was to evaluate the effectiveness of an audio and animated cartoon questionnaire (AACQ) at improving consent process in child for biospecimen donation. A multi-center randomized and controlled survey was performed at two pediatric hospitals in China from 2019 to 2020. Children aged from 7 to 18 years in the pediatric surgery wards were invited to investigate the participants' willingness and attitudes for donating biospecimens. A total of 264 children, including 119 in the AACQ group and 145 in the TQ group, and 67 parents of children were analyzed. A separate knowledge test was acquired in the questionnaires. Our findings showed that the response rate of the AACQ group (89.85%) was significantly higher than that of the TQ group (68.44%; p < 0.001). AACQ can improve the child's understanding, increase children's engagement in biospecimen donation, reduced the differences in selected characteristics affecting children understanding, and enhanced their risk awareness of donating biospecimens. We also found that increasing pain and privacy disclosure were the most popular concern among children for the refusal to donate biospecimens. AACQ is an effective and standardized tool of content delivery to children from the surgical wards. Children who fully understood of biospecimen donation are suggested to participate in the consent signing. Using audio and animated cartoon questionnaire is a more effective and standardized tool of content delivery to children. This study expanded the use of an animated cartoon to a children's survey. Audio and animated cartoon questionnaire (AACQ) can improve the child's understanding, increase children's engagement in biospecimen donation compared to text questionnaire (TQ) group, and enhanced their risk awareness of donating biospecimens. More AACQ should be used with children in the future to effectively deliver content to children and improve children's participation in the survey.


Cannula and Pump Positions Are Associated With Left Ventricular Unloading and Clinical Outcome in Patients With HeartWare Left Ventricular Assist Device.
Cannula and pump positions are associated with clinical outcomes such as device thrombosis in patients with HeartMate II; however, clinical implications of HVAD (HeartWare International, Framingham, Massachusetts) cannula position are unknown. This study aims to assess the relationship among cannula position, left ventricular (LV) unloading, and patient prognosis. Twenty-seven HVAD patients (60.0 ± 12.6 years of age and 19 males [70%]) underwent ramp test. Device position was quantified from chest X-ray parameters obtained at the time of the hemodyamic ramp test: (1) cannula coronal angle, (2) pump depth, (3) cannula sagittal angle, and (4) pump area. Lower cannula coronal angle was associated with LV unloading (as measured by smaller LV diastolic dimension and lower pulmonary capillary wedge pressure). Smaller pump area was associated with LV dynamic unloading, as assessed by steeper negative slopes of LV diastolic dimension and pulmonary capillary wedge pressure during incremental rotational speed change. Cannula coronal angle ≤65° was associated with reduced heart failure readmission rate (hazard ratio, 10.33; P = .007 by log-rank test). HVAD cannula and pump positions are associated with LV unloading and improved clinical outcomes. Prospective studies evaluating surgical techniques to ensure optimal device positioning and its effects on clinical outcomes are warranted.


Effects of diets high in saturated fat and cholesterol on the lipid composition of canine platelets.
The phospholipid composition of platelets from dogs on various experimental diets was determined. Thyroidectomized foxhounds were fed a control diet or the control diet supplemented with (1) beef tallow, (2) beef tallow and cholesterol, or (3) beef tallow, cholesterol, and safflower oil for 23 weeks prior to isolation of platelets. Platelets from animals fed the control diet contained 36.7% phosphatidylcholine (PC), 22.8% phosphatidylethanolamine (PE), 18.4% sphingomyelin (Sph), 11.8% phosphatidylserine (PS), 6.3% phosphatidylinositol (PI), and 2.2% lysophosphatidylcholine. The PE was 77.6% in the plasmalogen form. No highly significant changes in the phospholipid class composition resulted from the experimental diets. Cholesterol supplementation of the diets, however, caused consistent alterations in the fatty acid compositions of the platelet phospholipids including increases in the percentages of 18:1 omega 9 (oleic acid), 18:2 omega 6 (linoleic acid), and 20:3 omega 6 (homo-gamma linolenic acid) and a decrease in the percentage of 20:4 omega 6 (arachidonic acid). Addition of safflower oil to the tallow-cholesterol diet partially reversed these effects. These cholesterol-induced alterations in fatty acid composition could be due to exchange with plasma lipids, de novo synthesis, or altered platelet metabolism. The mechanism remains to be determined.


Prevention of infection and graft-versus-host disease by suppression of intestinal microflora in children treated with allogeneic bone marrow transplantation.
The effect of suppression with antimicrobial agents of the intestinal microflora of paediatric bone marrow graft recipients on severe bacterial and fungal infections and on moderate to severe acute graft-versus-host disease was studied retrospectively. Data on 65 cases of bone marrow transplantation for either severe bone marrow failure or leukaemia, performed in a strict protective environment with either complete or selective gastrointestinal decontamination, were evaluated. All bone marrow grafts were from HLA-identical siblings and were not depleted of T-lymphocytes. Twenty percent of the recipients had one or more episodes of septicaemia during the granulocytopenic period after transplantation, mostly due to gram-positive bacteria. Only five children died due to infection, in each case caused by a microorganism originating from the endogenous flora. Complete gastrointestinal decontamination was superior to selective gastrointestinal decontamination in preventing infectious complications (p less than 0.001). The same was the case for the prevention of acute graft-versus-host disease of grade II or higher, which was observed in 7 of 40 (17.5%) completely decontaminated children versus 9 of 18 (50%) selectively decontaminated children evaluable for graft-versus-host disease (p less than 0.01). It is concluded that complete gastrointestinal decontamination in a strict protective environment is a feasible and very effective method for preventing severe infections and acute graft-versus-host disease after allogeneic bone marrow transplantation in children and adolescents; it resulted in a low transplantation-related mortality of 26% and a good quality of survival in 69% of the graft recipients.


Catheter navigation by intracardiac echocardiography enables zero-fluoroscopy linear lesion formation and bidirectional cavotricuspid isthmus block in patients with typical atrial flutter.
One of the most helpful aspects of intracardiac echocardiography (ICE) implementation in electrophysiological studies (EPS) is the real-time visualisation of catheters and cardiac structures. In this prospective study, we investigated ICE-guided zero-fluoroscopy catheter navigation during radiofrequency (RF) ablation of the cavotricuspid isthmus (CTI) in patients with typical atrial flutter (AFL). Thirty consecutive patients (mean age 72.9 ± 11.4 years, 23 male) with ongoing (n = 23) or recent CTI-dependent AFL underwent an EPS, solely utilizing ICE for catheter navigation. Zero-fluoroscopy EPS could be successfully accomplished in all patients. Mean EPS duration was 41.4 ± 19.9 min, and mean ablation procedure duration was 20.8 ± 17.1 min. RF ablation was applied for 6.0 ± 3.1 min (50W, irrigated RF ablation). Echocardiographic parameters, such as CTI length, prominence of the Eustachian ridge (ER), and depth of the CTI pouch on the ablation plane, were assessed to analyse their correlation with EPS- or ablation procedure duration. The CTI pouch was shallower in patients with an ablation procedure duration above the median (4.8 ± 1.1 mm vs. 6.4 ± 0.9 mm, p = 0.04), suggesting a more lateral ablation plane in these patients, where the CTI musculature is stronger. CTI length or ER prominence above the respective median did not correlate with longer EPS duration. Zero-fluoroscopy CTI ablation guided solely by intracardiac echocardiography in patients with CTI-dependent AFL is feasible and safe. ICE visualisation may help to localise the optimal ablation plane, detect and correct poor tissue contact of the catheter tip, and recognise early potential complications during the ablation procedure.


Liver function of dairy cows in late pregnancy and early lactation.
The possibility that alterations in liver function may occur during late pregnancy as well as after calving has been investigated in healthy dairy cows and the results compared with those from non-pregnant non-lactating cows. There were significant alterations in plasma total bilirubin, glucose, total ketone body and urea concentrations, in bromsulphthalein clearance and in plasma aspartate aminotransferase and creatine kinase activities in periparturient cows compared with non-pregnant non-lactating cows. Of these, only the alterations in glucose, ketone bodies and urea concentrations and bromsulphthalein half-time and retention were markedly different before calving. The degree of fatty infiltration of the liver was significant two weeks before as well as two weeks after calving which differed from previous reports. It seems likely that the changes in the liver in dairy cows are functional and reversible and related to the metabolic demands of late pregnancy and early lactation. The results suggest that such changes in the liver occur well before calving.


Environmentally induced variation in body size of turtles hatching in natural nests.
Eggs from three snapping turtles (Chelydra serpentina) were divided between two natural nests in a factorial experiment assessing the role of the nest environment as a cause for variation in body size and energy reserves of hatchlings at our study site in northcentral Nebraska. Nest # 1 was located in an unshaded area on the south side of a high sandhill, whereas nest #2 was located in an unshaded area on level ground. Eggs in nest #1 increased in mass over the course of incubation, with eggs at the bottom of the nest gaining more mass than eggs nearer to the surface. In constrast, eggs in nest #2 lost mass during incubation, with eggs at the bottom declining less in mass than eggs at the top of the cavity. Hatchlings from nest #1 were much larger (but contained smaller masses of unused yolk) than hatchlings from nest #2. Additionally, eggs from the lower layers in both nests tended to produce larger hatchings (but with smaller masses of unused yolk) than eggs from the upper layers. Thus, ecologically important variation in body size and nutrient reserves of hatchling snapping turtles results from variation in the environment among and within nests.


Foetal blood flow measured using phase contrast cardiovascular magnetic resonance--preliminary data comparing 1.5 T with 3.0 T.
Phase contrast cardiovascular magnetic resonance (PC CMR) has emerged as a clinical tool for blood flow quantification but its use in the foetus has been hampered by the need for gating with the foetal heart beat. The previously described metric optimized gating (MOG) technique has been successfully used to measure foetal blood flow in late gestation foetuses on a 1.5 T CMR magnet. However, there is increasing interest in performing foetal cardiac imaging using 3.0 T CMR. We describe our pilot investigation of foetal blood flow measured using 3.0 T CMR. Foetal blood flows were quantified in 5 subjects at late gestational age (35-38 weeks). Three were normal pregnancies and two were pregnancies with ventricular size discrepancy. Data were obtained at 1.5 T and 3.0 T using a previously described PC CMR protocol. After reconstruction using MOG, blood flow was quantified independently by two observers. Intra- and inter-observer reproducibility of flow measurements at the two field strengths was assessed by Pearson correlation coefficient (R(2)), linear regression and Bland Altman analysis. PC CMR flow measurements were obtained in 36 of 40 target vessels. Strong intra-observer agreement was obtained between measurements at each field strength (R(2) = 0.78, slope = 0.83 ± 0.11), with a mean bias of -1 ml/min/kg and 95% confidence limits of ±71 ml/min/kg. Inter-observer agreement was similarly high for measurements at both 1.5 T (R(2) = 0.86, slope = 0.95 ± 0.13, bias = 6 ± 52 ml/min/kg) and 3.0 T (R(2) = 0.88, slope = 0.94 ± 0.13, bias = 4 ± 47 ml/min/kg). Across all PC CMR measurements, SNR per pixel was expectedly higher at 3.0 T relative to 1.5 T (165 ± 50%). The relative differences in flow measurements between observers were low (range: 4-16%) except for pulmonary blood flow which showed much higher variability at 1.5 T (34%) versus that at 3.0 T (11%). This was attributed to the poorly visualized, small pulmonary vessels at 1.5 T, which made delineation inconsistent between observers. This is the first pilot study to measure foetal blood flow using PC CMR at 3.0 T. The flow data obtained were in good correlation with those measured at 1.5 T, both within and between observers. With increased SNR at 3.0 T, smaller pulmonary vessels were better visualized which improved inter-observer agreement of associated flows.


Localization of the preprosomatostatin-mRNA by in situ hybridization in the ewe hypothalamus.
The peptidergic neurohormone somatostatin (SRIF) derives from a precursor called preprosomatostatin (PPS) by proteolysis. We have isolated by RT-PCR and sequenced a partial cDNA coding for the ovine PPS. It contains a 348 base pairs coding sequence that shares strong similarities with previously cloned mammalian cDNAs. The ovine cDNA was used to synthesize radiolabeled cRNA to probe the PPS mRNA in the ewe hypothalamus by in situ hybridization. The PPS mRNA-containing cells are widely distributed in the hypothalamus. According to the number of silver grains over a cell, they show various staining intensities. The distribution of the PPS mRNA is in good agreement with that of the peptide previously determined using immunohistochemistry. The strongest labeled areas include the periventricular region of the paraventricular nucleus and the lateral division of the ventromedial nucleus. The difference in labeling intensity observed in the diverse populations of labeled neurons could reflect various levels of neuronal activity.


A Causal Gene for Seed Dormancy on Wheat Chromosome 4A Encodes a MAP Kinase Kinase.
Seed germination under the appropriate environmental conditions is important both for plant species survival and for successful agriculture. Seed dormancy, which controls germination time, is one of the adaptation mechanisms and domestication traits [1]. Seed dormancy is generally defined as the absence of germination of a viable seed under conditions that are favorable for germination [2]. The seed dormancy of cultivated plants has generally been reduced during domestication [3]. Bread wheat (Triticum aestivum L.) is one of the most widely grown crops in the world. Weak dormancy may be an advantage for the productivity due to uniform emergence and a disadvantage for the risks of pre-harvest sprouting (PHS), which decreases grain quality and yield [4]. A number of quantitative trait loci (QTLs) controlling natural variation of seed dormancy have been identified on various chromosomes [5]. A major QTL for seed dormancy has been consistently detected on chromosome 4A [6-13]. The QTL was designated as a major gene, Phs1, which could be precisely mapped within a 2.6 cM region [14]. Here, we identified a mitogen-activated protein kinase kinase 3 (MKK3) gene (designated TaMKK3-A) by a map-based approach as a candidate gene for the seed dormancy locus Phs1 on chromosome 4A in bread wheat. Complementation analysis showed that transformation of a dormant wheat cultivar with the TaMKK3-A allele from a nondormant cultivar clearly reduced seed dormancy. Cultivars differing in dormancy had a single nonsynonymous amino acid substitution in the kinase domain of the predicted MKK3 protein sequence, which may be associated with the length of seed dormancy.


The Peptide Microarray ChloroPhos1.0: A Screening Tool for the Identification of Arabidopsis thaliana Chloroplast Protein Kinase Substrates.
We designed the peptide microarray ChloroPhos1.0 to screen for substrates of chloroplast protein kinases. The peptides represented on the microarray were selected from phosphoproteomics data, and the identified chloroplast phosphopeptides were spotted as 15-mers on a glass slide with the phosphorylation site centered. Altogether, 905 distinct peptides from chloroplast proteins are present on the array. Here we describe how the array can be used to identify the target protein spectrum of chloroplast kinases. We present the method and discuss limitations and challenges associated with the determination of phosphorylation activity on peptide substrates in vitro.


Piezoelectric extracorporeal lithotripsy by ultrashort waves with the EDAP LT 01 device.
A total of 433 extracorporeal lithotripsy procedures was performed for renal, ureteral and bladder stones by means of a system of ultrasonographic detection and piezoelectric destruction in 386 patients. The stones were detected easily in 87 per cent of the patients, difficult to detect in 10 per cent and impossible to detect in 3 per cent. Mean duration of treatment was 35 minutes. Mean number of piezoelectric waves was 2,700 at 1.25 per second. With a frequency of 1.25 to 5 per second, extracorporeal lithotripsy was performed without any local, regional or general anesthesia, and without premedication in 210 patients. Of the 217 patients with a renal stone reviewed at 3 months 161 (74 per cent) had successful results and 56 (26 per cent) failed therapy. Thirty patients (14 per cent) underwent 2 or 3 sessions. The morbidity was low: 2 per cent of the patients suffered ureteral obstruction, 1.5 per cent had subcapsular hematoma and 4 per cent had fever. No significant modifications of laboratory tests were necessary and no patient suffered renal failure. Of the stones 31 in the lumbar ureter, 15 in the pelvic ureter and 8 in the bladder were treated, with success rates of 87, 46 and 50 per cent, respectively. A total of 103 patients was treated on an outpatient basis. This outpatient treatment, together with the low cost and minimal maintenance of the apparatus, and the absence of anesthesia constitute a new progress in the treatment of renal stones.


Biogenesis and function of rice small RNAs from non-coding RNA precursors.
Non-coding RNAs, especially small RNAs, play important roles in many biological processes. Several small RNA types, including microRNAs (miRNAs) and small interfering RNAs (siRNAs), are well-described in rice (Oryza sativa), although much remains to be learned about their function. Many small RNAs along with their targets have been characterized with deep sequencing technologies. Some special classes of these small RNAs have been found to be unique to rice or within the larger group of grasses. The functional and biological roles of numerous plants small RNAs have been described in detail, including functions as varied as the regulation of tissue development, phase transition, or abiotic and biotic stress resistance. Mutant analysis has proven useful in the genetic identification of components involved in small RNA biogenesis and also in identification of regulatory functions of small RNAs. Although many small RNAs have been identified by deep sequencing in rice, their precise regulatory functions and cell-type specificity are in many cases still unknown.


Mapping ecological processes and ecosystem services for prioritizing restoration efforts in a semi-arid Mediterranean river basin.
Semi-arid Mediterranean regions are highly susceptible to desertification processes which can reduce the benefits that people obtain from healthy ecosystems and thus threaten human wellbeing. The European Union Biodiversity Strategy to 2020 recognizes the need to incorporate ecosystem services into land-use management, conservation, and restoration actions. The inclusion of ecosystem services into restoration actions and plans is an emerging area of research, and there are few documented approaches and guidelines on how to undertake such an exercise. This paper responds to this need, and we demonstrate an approach for identifying both key ecosystem services provisioning areas and the spatial relationship between ecological processes and services. A degraded semi-arid Mediterranean river basin in north east Spain was used as a case study area. We show that the quantification and mapping of services are the first step required for both optimizing and targeting of specific local areas for restoration. Additionally, we provide guidelines for restoration planning at a watershed scale; establishing priorities for improving the delivery of ecosystem services at this scale; and prioritizing the sub-watersheds for restoration based on their potential for delivering a combination of key ecosystem services for the entire basin.


Assessment of upper extremity-injured persons' return to work potential.
Therapists specializing in the rehabilitation of persons with upper extremity disorders--hand therapists--have developed an evaluation procedure to determine if and when an injured worker has the physical capacity to safely return to work. The Return to Work Evaluation has five components: (1) physical evaluation, (2) subjective effects of injury interview, (3) biomechanical job analysis, (4) work stimulation, (5) reevaluation. The therapist designs a work simulation based on the identification of the critical physical demand characteristics of the patient's work. After documenting the patient's response to the work simulation, the therapist formulates recommendations to the physician with regard to the patient's ability to safely return to the workplace. These recommendations may include the need for job/worker modifications or the need for a reconditioning program. The implementation of the Return to Work Evaluation has decreased the physician's liability in return-to-work decisions and has allowed injured workers to maintain optimal function after medical treatment.


Transmitter biochemistry and histochemistry of the hypoplastic cerebellum in mice after neonatal administration of cytosine arabinoside.
Administration of cytosine arabinoside, a DNA polymerase inhibitor, to mice (50 mg/kg body weight) on postnatal days 2, 3 and 4 resulted in severe hypoplasia of the cerebellar cortex accompanied by a large decrease in the cerebellar DNA and RNA contents. On postnatal days 10, 20, 30 and 70, concentrations of the putative neurotransmitters, noradrenaline and serotonin, were significantly increased in the affected cerebellum. In contrast, gamma-aminobutyric acid concentration was little changed, although a decrease in the content of gamma-aminobutyric acid per cerebellum was observed from postnatal day 20. No changes were found in the concentrations of these transmitter candidates nor in dopamine in the cerebral cortex or the brain stem. Histofluorescence observations revealed abnormally dense noradrenergic fibers in a poorly organized cerebellar cortex. The distribution of these fibers was characterized by a honeycomb pattern in the Purkinje cell and granular layers, and a dense plexus in the lower part of the thin molecular layer. However, the significance of neither the density of the noradrenergic fibers nor their abnormal distribution was apparent from the results of this study.


Regioselective palladium cross-coupling of 2,4-dihalooxazoles: convergent synthesis of trisoxazoles.
A regioselective Suzuki-Miyaura cross-coupling of 2,4-dihalooxazoles followed by a Stille coupling has been successfully developed. The procedure affords convergent syntheses of trisoxazoles in high yield and in a minimum number of steps.


Exercise in hypertensive children and adolescents: any harm done?
Hypertensive children and adolescents are frequently arbitrarily excluded from sports or exercise because of the fear of possible complications, such as stroke or myocardial infarction. No hypertensive children have had exercise-related morbidity or mortality in the reviewed literature. No restriction from dynamic exercise seems warranted; training has led to reductions in blood pressure in hypertensive youth. Isometric exercise is more hotly debated. Because no complications of exercise have been reported, the author prefers to allow participation if no target organ damage is present. Life-long maintenance of habitual physical activity may help prevent adult-onset essential hypertension.


Phenolic composition and correlation with antioxidant properties of various organic fractions from Hertia cheirifolia extracts.
Hertia cheirifolia L. is a medicinal plant that has been used for a long time in folk Mediterranean medicine. The aim of the present study was to analyze and compare the phenolic profile and the antioxidant potential of organic fractions from H. cheirifolia extracts. Crude methanolic extracts were firstly prepared from the different parts of the plant. Then four different organic fractions were obtained by fractioning each extract, using different solvents with increasing polarity (hexane, chloroform, and ethyl acetate). The Phenolic content was analyzed using a UV-Vis colorimetric methods followed by a qualitative and quantitative analysis by high performance liquid chromatography-diode array detector (HPLC-DAD) system. After that, the antioxidant potential of the different organic fractions was evaluated using DPPH and ABTS free radical scavenging assays, reducing power of iron (FRAP) and inhibition of β-carotene oxidation tests. Our results revealed that ethyl acetate fractions (EA) contained the highest content of total phenolics (100-250 mg GAE/g). Indeed, the ethyl acetate fraction from the flower extract (EA-F) displayed the lowest IC50 values for the scavenging of DPPH and ABTS free radicals (38.83 ± 0.34 µg/ml and 23.76 ± 0.11 µg/ml, respectively). Also, the strongest iron reducing power (2628.87 ± 16.47 µmol Fe2+Eq/ml) and the best rate of inhibition of the β-carotene oxidation (58.91 ± 5.79 %) were recorded. In sum, the present study suggests that, the organic fractions from H. cherifolia are potential natural antioxidants and this is probably related to their phenolics content and structure.


Current situation of scrub typhus in South Korea from 2001-2013.
The bacteria Orientia tsutsugamushi is the causative agent of scrub typhus, mite-borne disease, which causes an acute febrile illness in patients. An epidemiologic study was conducted to understand the characteristics of scrub typhus in South Korea. Reporting of tsutsugamushi disease is mandatory in South Korea since 1994. To investigate the prevalence of tsutsugamushi disease from 2001 to 2013, medical records from the Korea Center for Disease Control and Prevention were reviewed. In total, 70,914 cases were reported during 2001-2013. Of these, 37.16% (26,349) were male and 62.84% (44,565) were female. The highest number of cases was in the 60-69-year-old age group (19,484; 27.48%), and 72.22% (51,212) were in the 50-79-year-old age group. There were 65,100 cases (91.80%) reported during October (24,964; 35.20%) and November (40,136; 56.60%). An almost four-fold increase in the number of patients was observed in 2013 (10,485 cases) compared to 2001 (2,637 cases). The highest number of patients was reported in the Jeonbuk (9,425; 13.29%) and lowest in the Jeju (362; 0.51%). A rapid increase in the incidence of patients with tsutsugamushi disease was observed in most areas from 2001 to 2013, with the majority of cases reported in the western and southern coast.


Dissociation of glucocorticoid effects of C-21 steroids at high concentrations in thymocytes.
A dissociation between inhibition of RNA synthesis and cell lysis was observed when thymocytes of adrenalectomized rats were incubated with high concentrations of pregn-4-ene-11 beta-ol-3,20-dione and pregna-1,4-diene-11 beta-ol-3,20-dione. In contrast, no dissociation of these effects was found with the typical glucocorticoids cortisol and corticosterone, nor with their 1,4-diene analogs under the same conditions.


K-Pro: Kinetics Data on Proteins and Mutants.
The study of protein folding plays a crucial role in improving our understanding of protein function and of the relationship between genetics and phenotypes. In particular, understanding the thermodynamics and kinetics of the folding process is important for uncovering the mechanisms behind human disorders caused by protein misfolding. To address this issue, it is essential to collect and curate experimental kinetic and thermodynamic data on protein folding. K-Pro is a new database designed for collecting and storing experimental kinetic data on monomeric proteins, with a two-state folding mechanism. With 1,529 records from 62 proteins corresponding to 65 structures, K-Pro contains various kinetic parameters such as the logarithm of the folding and unfolding rates, Tanford's β and the ϕ values. When available, the database also includes thermodynamic parameters associated with the kinetic data. K-Pro features a user-friendly interface that allows browsing and downloading kinetic data of interest. The graphical interface provides a visual representation of the protein and mutants, and it is cross-linked to key databases such as PDB, UniProt, and PubMed. K-Pro is open and freely accessible through https://folding.biofold.org/k-pro and supports the latest versions of popular browsers.


Identification of a nucleo-cytoplasmic ionic pathway by osmotic shock in isolated mouse liver nuclei.
The observation that the nuclear envelope outer membrane contains ion channels raises the question of whether these conductances communicate between the cytosol and the nuclear envelope cisternae or between the cytosol and the cytoplasm. Failure to detect large, nonselective holes using the patch-clamp technique has led to the speculation that ion channels and nuclear pores are in fact the same. In this paper we present evidence that the ionic channel, recorded in isolated liver nuclei with the patch-clamp configuration of "nucleus-attached," spans the double membrane of the envelope, providing a direct contact between nucleoplasm and cytoplasm.


Midterm Results after Open Surgical and Endovascular Management of Arterioureteral Fistula.
Arterioureteral fistula refers to the anomalous fistulous connection between the iliac artery and the ureter. It is often associated with pelvic malignancy, abdominal surgery, and radiation. As it is a potentially life-threatening condition, prompt diagnosis and management is essential. We performed a retrospective analysis of patients treated for arterioureteral fistula in a single-vascular institution from January 2013 to March 2019. Preoperative assessment included physical and laboratory examinations and medical history, with diagnosis established through computed tomography angiography, digital subtraction angiography, or ureteroscopy. Parameters analyzed included perioperative mortality and morbidity as well as treatment durability during midterm follow-up. Nine patients with ten arterioureteral fistulas were included in the study. Macroscopic hematuria was the main presenting symptom, with 2 patients admitted due to hemorrhagic shock. Endovascular treatment was carried out in 6 patients. In 4 cases, single stent-graft deployment inside the common iliac artery was performed, in one case in combination with plugging of the internal iliac artery. One patient underwent implantation of an iliac-branched device, whereas in another patient coiling of the internal iliac artery sufficed for management of the fistula. Open surgical repair was carried out in three cases. Perioperative mortality was zero; one patient had prolonged hospital stay due to superficial wound infection. Recurrent hematuria and stent-graft infection were observed during follow-up in three patients after endovascular repair, all of them treated through open surgery with no further complications. One patient developed an enterocutaneous fistula after open repair during follow-up and required redo surgery. Arterioureteral fistula is a challenging clinical scenario demanding prompt diagnosis and management. Open surgery remains the treatment of choice in cases of preexisting vascular reconstruction or manifest infection. Endovascular techniques offer a viable solution in significantly comorbid patients or in patients presenting with acute, life-threatening bleeding. Rigorous follow-up is required regardless of treatment modality due to the considerable rate of reinterventions.


The Living Kidney Donor Safety Study: Protocol of a Prospective Cohort Study.
Living kidney donation is considered generally safe in healthy individuals; however, there is a need to better understand the long-term effects of donation on blood pressure and kidney function. To determine the risk of hypertension in healthy, normotensive adults who donate a kidney compared with healthy, normotensive non-donors with similar indicators of baseline health. We will also compare the 2 groups on the rate of decline in kidney function, the risk of albuminuria, and changes in health-related quality of life. Prospective cohort study of 1042 living kidney donors recruited before surgery from 17 transplant centers (12 in Canada and 5 in Australia) between 2004 and 2014. Non-donor participants (n = 396) included relatives or friends of the donor, or donor candidates who were ineligible to donate due to blood group or cross-match incompatibility. Follow-up will continue until 2021, and the main analysis will be performed in 2022. The anticipated median (25th, 75th percentile, maximum) follow-up time after donation is 7 years (6, 8, 15). Donors and non-donors completed the same schedule of measurements at baseline and follow-up (non-donors were assigned a simulated nephrectomy date). Annual measurements were obtained for blood pressure, estimated glomerular filtration rate (eGFR), albuminuria, patient-reported health-related quality of life, and general health. Incident hypertension (a systolic/diastolic blood pressure ≥ 140/90 mm Hg or receipt of anti-hypertensive medication) will be adjudicated by a physician blinded to the participant's donation status. We will assess the rate of change in eGFR starting from 12 months after the nephrectomy date and the proportion who develop an albumin-to-creatinine ratio ≥3 mg/mmol (≥30 mg/g) in follow-up. Health-related quality of life will be assessed using the 36-item RAND health survey and the Beck Anxiety and Depression inventories. Donation-attributable hypertension may not manifest until decades after donation. This prospective cohort study will estimate the attributable risk of hypertension and other health outcomes after living kidney donation.


Rare occurrence of mix stromal tumours: a case report of gastrointestinal and extra-intestinal stromal tumour on the jejunum and omentum of a nine year old girl from Adamawa State, Nigeria.
Stromal tumors of the jejunum (GIST) and omentum (EGIST) are uncommon and dearth of information still exists on their occurrence concurrently. Here, we report a nine year old girl that presented with tender abdominal mass measuring 14 × 8 cm associated with features of gastric outlet obstruction and hyponatremia of 115mmol/L. A diagnosis of hyponatremia in a child with gastric outlet obstruction secondary to intraabdominal mass was made for which exploratory laparotomy was carried out. Histology of the tumour revealed stromal spindle epithelioid as well as myxoid cells. Complete resection of the tumour and correction for hyponatremia was done in addition to antibiotics therapy with remarkable improvement. Index case is that of mixed stromal tumours that presented with features of gastric outlet obstruction, and the patient did well after surgery.


Application of PCR-SSCP for molecular epidemiological studies on the exposure of farm children to bacteria in environmental dust.
The environmental exposure of farm children to microorganisms in dust has become a focus of interest, since microbial exposure on farms has been related to a reduced prevalence of asthma and atopic diseases in children. Previous studies almost exclusively focused on the determination of microbial counts using conventional culturing or the determination of microbial compounds i.e. endotoxins. In this study PCR-SSCP (single-strand conformation polymorphism) was modified for characterising bacterial communities in environmental dusts and their sensitivity and reproducibility was validated. A fivefold repeated PCR-SSCP analyses of a well homogenised mattress dust, cow-shed dust, swine-shed dust, chicken-shed dust and a horse-shed dust sample, respectively, showed similarities, based on Pearson correlations, ranging from 89.7% to 95.2%. The reproducibility of day to day variations (five days) and gel to gel variations (five gels) was also around 90%. The detection limit of Escherichia coli was 7 x 10(1) cfu g(-1) whereas Listeria monocytogenes and Bacillus licheniformis containing 30% spores showed visible bands at 7 x1 0(2) cfu g(-1). Application of this method to dust samples of 37 sheds and 63 children's mattresses showed that distinct farm environment dusts reflected different SSCP profiles. However, digital analysis of the gels showed that some bands in the profiles of shed- and mattress dusts were found at the same position in the gels. By excision, cloning, sequencing and phylogenetic analyses, these bands were identified as Corynebacterium tuberculostearicum, Corynebacterium mucifaciens, Staphylococcus epidermidis, Acinetobacter lwoffii, Brevibacterium iodinum, Brevibacterium linens and Arthrobacter spp, respectively. These results may reflect transfer of microorganisms from animal sheds to mattresses. In conclusion this study demonstrates that PCR-SSCP is a promising method with sensitive detection limits and moderate sample variances to be applied for epidemiological studies characterizing the exposure of farmers using environmental dust.


[Consensus document by the Spanish Society of Paediatric Infectious Diseases and the advisory committee on vaccines of the Spanish Paediatrics Association on vaccination in immunocompromised children].
Vaccination in immunocompromised infants, children and adolescents is a major aspect in the follow-up of this complex pathology in specific Paediatric Units. Vaccination is also an important prevention tool, as this can, to a certain extent, determine the morbidity and mortality in these patients. This consensus document was jointly prepared by Working Groups of the Spanish Society of Paediatric Infectious Diseases and the Advisory Committee on Vaccines of the Spanish Paediatric Association, who are usually involved in updating the management of vaccinations in immunocompromised children, and reflects their opinions. The consensus specifically summarises indications for vaccination in the following special paediatric populations: Solid organ and haematopoietic transplant-recipients; primary immunodeficiency; asplenic children; non-previously transplanted immunocompromised patients; chronically ill patients; HIV-infected children and also the vaccines recommended for immunodeficient children who travel.


Treatment of acute myeloid leukemia developing after a myelodysplastic phase with low dose arabinosyl cytosine.
Patients with acute myeloid leukemia (AML) secondary to myelodysplastic phase respond poorly to standard chemotherapy designed for AML. As arabinosyl cytosine (Ara-C) at low-dose has been reported to achieve promising results in certain forms of AML, we have applied the low-dose (10 mg m-2/12 h subcutaneously for 14-24 days) regimen in 11 patients with AML secondary to myelodysplastic syndromes. Though a complete remission could be achieved in 2 patients and a short partial remission in 2 further patients, complications are severe and often life threatening. The amount of hematological supportive care required often exceeded that needed for patients treated by conventional TAD regimen. Moreover, survival of the responders did not seem to be longer than that of non-responders. A review of the literature showed that the results of this low-dose Ara-C regimen might be more promising in patients in the myelodysplastic phase and in those with de novo acute leukemia.


Stable and Efficient Red Perovskite Light-Emitting Diodes Based on Ca2+-Doped CsPbI3 Nanocrystals.
α-CsPbI3 nanocrystals (NCs) with poor stability prevent their wide applications in optoelectronic fields. Ca2+ (1.00 Å) as a new B-site doping ion can successfully boost CsPbI3 NC performance with both improved phase stability and optoelectronic properties. With a Ca2+/Pb2+ ratio of 0.40%, both phase and photoluminescence (PL) stability could be greatly enhanced. Facilitated by increased tolerance factor, the cubic phase of its solid film could be maintained after 58 days in ambient condition or 4 h accelerated aging process at 120°C. The PL stability of its solution could be preserved to 83% after 147 days in ambient condition. Even using UV light to accelerate aging, the T50 of PL could boost 1.8-folds as compared to CsPbI3 NCs. Because Ca2+ doping can dramatically decrease defect densities of films and reduce hole injection barriers, the red light-emitting diodes (LEDs) exhibited about triple enhancement for maximum the external quantum efficiency (EQE) up to 7.8% and 2.2 times enhancement for half-lifetime of LED up to 85 min. We believe it is promising to further explore high-quality CsPbI3 NC LEDs via a Ca2+-doping strategy.


[Atrial fibrillation : new anticoagulants and antiarrhythmic drugs].
Atrial fibrillation is the most common form of arrhythmia and one of the most frequent causes of ischemic stroke. Several new anticoagulants have recently been introduced as alternatives to vitamin-K antagonists for prophylaxis of ischemic stroke and tested in phase-3 studies for efficacy and safety. Identifying patients who will profit in particular from the new anticoagulant therapy is crucial to the clinical application of these drugs. Vernakalant and dronedarone are new antiarrhythmic drugs for rhythm control of atrial fibrillation. However, therapeutic efficacy of the new agents still has to be proven.


Lithium adsorption by acid and sodium amberlite.
In this paper we used a previously reported model for examining the adsorption of nonelectrolytes in solution by solid adsorbents to study the adsorption of lithium(I) cations by acid and sodium amberlites, which is an ion-exchange process. Based on the results, both are equilibrium processes and obey a kinetic law with a unity partial order in the Li+ concentration. The kinetic results were used to calculate the specific rate constants and thermodynamic activation functions involved. Also, equilibrium isotherms were used to determine the corresponding ion-exchange capacities, the individual equilibrium constants, and the thermodynamic functions for the overall process.


TNFRSF13B in B cell responses to organ transplantation.
Antibodies directed against organ transplants are thought to pose the most vexing hurdle to enduring function and survival of the transplants, particularly organ xenotransplants, and accordingly basic and clinical investigation has focused on elucidating the specificity and pathogenicity of graft-specific antibodies. While much has been learned about these matters, far less is known about the B cells producing graft-specific antibodies and why these antibodies appear to injure some grafts but not others. With the goal of addressing those questions, we have investigated the properties of tumor necrosis factor receptor super family-13B (TNFRSF13B), which regulates various aspects of B cell responses. A full understanding of the functions of TNFRSF13B however is hindered by extreme polymorphism and by diversity of interactions of the protein. Nevertheless, TNFRSF13B variants have been found to exert distinct impact on natural and elicited antibody responses and host defense and mutations of TNFRSF13B have been found to influence the propensity for development of antibody-mediated rejection of organ transplants. Because B cell responses potentially limit application of xenotransplantation, understanding how TNFRSF13B diversity and TNFRSF13B variants govern immunity in xenotransplantation could inspire development of novel therapeutics that could in turn accelerate clinical implementation of xenotransplantation.


Calbindin-D 28K in hippocampal organotypic cultures.
Slices of hippocampus from 6-day-old rats were cultured for 2-4 weeks using the roller-tube technique. The organization of these explants was studied by immunocytochemical labeling of calbindin-D 28K (CaBP 28K). The development of the CaBP 28K staining was very close to that of the rat hippocampus in vivo with only 3 subpopulations of labeled cells: granule cells and their mossy fibers, pyramidal cells in the subiculum-CA1 zone and interneurons scattered in strata oriens and radiatum.


Activation of the high affinity nerve growth factor receptor by two polyanionic chemotherapeutic agents: role in drug induced neurotoxicity.
Suramin is a polyanionic chemotherapeutic agent which causes severe peripheral neuropathy. The mechanisms of antineoplastic and neurotoxic activities are still poorly understood. Interference with growth factor receptor function has been suggested for suramin's chemotherapeutic function. Previous studies from our laboratory have demonstrated that suramin interfered with the function of nerve growth factor (NGF) and induced lysosomal storage defects within dorsal root ganglion neurons. Pentosan polysulfate (PPS) was used as another polyanionic agent, to compare these two cellular functions; NGF receptor interaction and disruption in glycolipid metabolism. Like suramin and NGF, PPS induced neurite outgrowth from the PC12 cell line which correlated with tyrosine phosphorylation of the high affinity NGF receptor (TrkA/gpl40) and ERK-1/MAP kinase. Ultrastructural studies of dorsal root ganglion exposed to PPS for various time periods were normal. This contrasted with suramin exposed cultures which consistently developed lamellar inclusion bodies (LIB) within 6 h. LIB formation with suramin treatment was associated with neuronal cell death, while PPS treatment did not cause any neurotoxic effects. These results indicated that PPS mimicked the effect of suramin on NGF receptors but did not cause similar accumulation of LIB. This suggested that the effect of polyanionic compounds on TrkA was not involved in LIB accumulation and subsequent induction of neurotoxicity.


Triggering due to de Quervain's disease.
Triggering of the thumb due to de Quervain's disease is a rarity. When it occurs in a boy of seven years old, it has never been reported before in the English literature.


Acute macular neuroretinopathy.
A 17-year-old boy had minor visual impairment, paracentral scotomata, and parafoveal retinal lesions following a presumed viral infection. Contact lens biomicroscopy demonstrated the retinal defects to be located at the level of the deep sensory retina. Fluorescein angiography revealed subtle areas of hypofluorescence which corresponded to the visible disturbances of the sensory retina. Follow-up examination three months later revealed persistent complaints of paracentral scotomata and persistent, but less recognizable retinal lesions. We believe the primary site of involvement to be the deep sensory retina.


[The Veterinary Drug Act and the practice for domestic animals].
A general discussion of some matters which were factors in passing the Veterinary Medicinal Products Act is followed by a consideration of the consequences of the Act for companion animal practices.


Cell wall composition of tomato fruit changes during development and inhibition of vesicle trafficking is associated with reduced pectin levels and reduced softening.
Fruit development entails a multitude of biochemical changes leading up to the mature green stage. During this period the cell wall will undergo complex compositional and structural changes. Inhibition of genes encoding elements of the machinery involved in trafficking to the cell wall presents us with a useful tool to study these changes and their associated phenotypes. An antisense SlRab11a transgene has previously been shown to reduce ripening-associated fruit softening. SlRab11a is highly expressed during fruit development which is associated with a period of pectin influx into the wall. We have analysed the cell wall polysaccharides at different stages of growth and ripening of wild type and antisense SlRab11a transgenic tomato (Solanum lycopersicum cv, Ailsa Craig) fruit. Our results demonstrated intriguing changes in cell wall composition during the development and ripening of wild type Alisa Craig tomato fruit. Analysis of SlRab11a expression by TaqMan PCR showed it to be expressed most strongly during growth of the fruit, suggesting a possible role in cell wall deposition. The SlRab11a antisense fruit had a decreased proportion of pectin in the cell wall compared with the wild type. We suggest a new approach for modification of fruit shelf-life by changing cell wall deposition rather than cell wall hydrolytic enzymes.


Control of plant cell differentiation by histone modification and DNA methylation.
How cells differentiate and acquire diverse arrays of determined states in multicellular organisms is a fundamental and yet unanswered question in biology. Molecular genetic studies over the last few decades have identified many transcriptional regulators that activate or repress gene expression to promote cell differentiation in plant development. What has recently emerged as an additional important regulatory layer is the control at the epigenetic level by which locus-specific DNA methylation and histone modification alter the chromatin state and limit the expression of key developmental regulators to specific windows of time and space. Accumulating evidence suggests that histone acetylation is commonly linked with active transcription and this mechanism is adopted to control sequential progression of cell differentiation. Histone H3 trimethylation at lysine 27 and DNA methylation are both associated with gene repression, and these mechanisms are often utilised to promote and/or maintain the differentiated status of plant cells.


Arteriohepatic dysplasia (Alagille syndrome; Watson-Alagille syndrome).
Alagille syndrome (AS) (arteriohepatic dysplasia, Alagille-Watson syndrome) is a multi-system disorder with hepatic, skeletal, eye, cardiac and renal manifestations. It results from mutation of the JAG1 gene, located on chromosome 20, which encodes a ligand for Notch receptor(s). The interactions of Notch receptors and their ligands are crucial in controlling cell fate decisions in a variety of developmental processes. AS varies in its severity, even in the same family, from asymptomatic gene carriers through to lethality due to inoperable cardiac or end-stage liver disease. However, advances in medical and surgical therapy have improved the prognosis at the severe end of the spectrum. It is hoped that the enhanced understanding of the biology of AS resulting from the cloning of the JAG1 gene will enable us to develop additional strategies for more effective treatments.


Advances in the treatment options for vitiligo: activated low-dose cytokines-based therapy.
Vitiligo is a skin disorder characterized by a progressive depigmentation, which is caused by the loss of melanocytes at the cutaneous level. A shift of the immune system with a prevalence of T helper (Th)1/Th17 response instead of a Tregs/Th2 one and may be part of etiology of 10 vitiligo. This review describes the major points of vitiligo onset and shows the cutting-edge results in the field of low-dose medicine in the treatment of dermatologic diseases and, in particular. in vitiligo. In this review on advances in vitiligo pharmacotherapy, the most pertinent recent publications are reported. Electronic databases such as PubMed were searched for terms 'low-dose medicine' or 'low dose and vitiligo' or 'low dose and psoriasis.' The availability of a systemic treatment for vitiligo, based on the oral administration of low-dose activated signaling molecules represents an opportunity for the dermatologists to overcome some specific pitfalls of currently available therapeutic protocols.


Potential determinant factors of sexual identity in ambiguous genitalia.
This is a review of literature scanning the potential factors which may affect Sexual Identity (S.I.) and Gender Identity (G.I.) in patients with ambiguous genitalia. Definitions of these concepts are outlined. Genetic, gonadal, hormonal, social and cultural pressures are reviewed as well as lessons to learn from clinical experiences and outcomes. Current criteriae used to assign gender in a child with ambiguous genitalia are discussed including medical and surgical criteriae as well as cultural disruptors. At the dawn of the third millennium, it is remarkable how little we know about the establishment of our individual and social identities.


Tumour characteristics among women with very low-risk breast cancer.
It has been proposed that a proportion of non-palpable breast cancers that are diagnosed through mammography represents a very low-risk subgroup of cancers that may not affect survival (overdiagnosis). The salient pathologic features of cancers in this theoretical subgroup are not known, and therefore, it is not possible to predict which patients have a cancer of this type. We reviewed the clinical characteristics and survival experiences of 715 patients with an invasive breast cancer of 5.0 cm or less. The tumour from each patient was represented in triplicate on a tissue microarray. Cases were divided into low-risk and moderate-/high-risk categories based on lymph node status and palpability. Low-risk cancers were those that were non-palpable, node-negative and were only detected by mammographic screening. All other cancers were high/moderate risk. The two groups of cancer patients were compared for a number of tumour characteristics, based on immunohistochemistry. There were 79 low-risk cancers and 636 moderate-/high-risk cancers. The low-risk cancers were characterized by ER-positivity, PR-positivity, HER2-negativity, ck5/6-negativity, EGFR-negativity and p53-negativity. About 54 of the 79 low-risk cancers (68 %) were of the luminal A subtype versus 335 of 636 moderate-/high-risk cancers (53 %; p = 0.008). Among 42 women with a non-palpable, mammogram-detected PR+ HER2- cancer of 5.0 cm or less, the 15-year distant recurrence-free survival rate was 100 %. Small breast cancers that are PR+ and HER2- and that are detectable by mammogram alone have a very low risk of recurrence. A proportion of these may represent examples of overdiagnosis.


Comparing the whole-genome-shotgun and map-based sequences of the rice genome.
The rice genome has now been sequenced using whole-genome-shotgun and map-based methods. The relative merits of the two methods are the subject of debate, as they were in the human genome project. In this Opinion article, we will show that the serious discrepancies between the resultant sequences are mostly found in the large transposable elements such as copia and gypsy that populate the intergenic regions of plant genomes. Differences in published gene counts and polymorphism rates are similarly resolved by considering how transposable elements affect the sequence analysis.


Improving fixation strength of pedicle screw by microarc oxidation treatment: an experimental study of osteoporotic spine in sheep.
Failure of fixation caused by loosening of pedicle screws in osteoporosis is a problem in spinal surgery. We compared the in vivo fixation strength between pedicle screws treated with microarc oxidation (MAO) and untreated screws in an osteoporotic model of ovariectomized sheep. The MAO treated and untreated screws were placed in lumbar vertebral bodies. After 3 months of implantation, biomechanical tests, micro-CT analysis, and histological observations were conducted to examine the performance of the two groups. At time 0, no significant difference was found between the two groups in biomechanical tests (p > 0.05); 3 months later, higher pull-out strength and load with less displacement were detected in the MAO-treated group (p < 0.05). Micro-CT analysis showed that the tissue mineral density, bone volume fraction, trabecular thickness, and trabecular number in the MAO-treated group were all higher than those in untreated group (p < 0.05), and trabecular spacing was smaller (p < 0.05). Histologically, the bone-implant interface in the MAO-treated group was better than that in untreated group (p < 0.05). In conclusion, pedicle screws with a bioactive surface treated by MAO can improve screw fixation strength in osteoporotic spines in sheep.