Physiological genetics, chemical composition, health benefits and toxicology of tea (Camellia sinensis L.) flower: A review.
The flower of tea (Camellia sinensis L.) plant has been paid an increasing attention in the last twenty years, since it was found that tea flowers contained representative constituents similar to those of tea leaves, such as catechins, caffeine and amino acids. Tea flower is theoretically valuable although it has been considered as an industrial waste over a long period of time. This review summarizes the research findings conducted until now on physiological genetics, chemical composition, health benefits and toxicology of tea flowers, aiming to foresee their future applications. A lot of genes are involved in flower development and the synthesis and transmission of various chemicals in tea flowers. The chemical composition of tea flower consists mainly of catechins, polysaccharides, proteins, amino acids and saponins and thus tea flower possesses various health benefits such as antioxidant, anti-inflammatory, immunostimulating, antitumor, hypoglycemic, anti-obesity and anti-allergic activities. Moreover, tea flower contains a protease that can elevate the free amino acids content in the tea infusion by almost two folds. More importantly, the enzymatic activity of the protease is much higher than that of the commercially available proteases. Additionally, aqueous extracts of tea flower are demonstrated to safe to animals. Thus, the potential uses of tea flowers in food and medical fields are warranted.


Association between MRI findings and clinical outcomes in a period of 5 years after lumbar spine microdiscectomy.
To evaluate the associations between magnetic resonance imaging (MRI) findings and pain, disability and quality of life before surgery and up to 5 years after lumbar microdiscectomy. Sixty-one patients who underwent one-level lumbar microdiscectomy by the same surgeon participated in this analytic, observational, prospective study. Lumbar spine MRI was performed preoperatively and 5 years postoperatively. Pain, disability and quality of life were measured with VAS, ODI, Roland Morris and SF-36 pre- and up to 5 years postoperatively. Subsequently associations between radiological findings and clinical outcomes were recorded. Before surgery patients with disc extrusion or sequestration, with increased thecal sac compression (d > 2/3), with Modic changes (MC) 2 and 3 on the operated level and Pfirrmann grades IV and V on the operated and both adjacent discs presented the worst preoperative clinical outcomes. MC preoperatively were not related with postoperative results, in contrast with the type of disc herniation and thecal sac compression. Preoperative Pfirrmann grade IV and V on the operated and both adjacent discs and postoperative MC 2 and 3 on the operated level were related to poor clinical outcomes 36-60 months post-discectomy. Extrusion or sequestration of the operated disc, increased compression of thecal sac, MC 2 and 3 on the operated level and Pfirrmann grades IV and V on the operated and adjacent discs were associated with the worst clinical outcomes. Nerve root impingement, facet joint arthritis, perineural fibrosis and disc granulation tissue had no effect on clinical scores.


Electrodiagnosis of carpal tunnel syndrome.
This article discusses the epidemiology and clinical presentation of carpal tunnel syndrome and the electrodiagnostic approach to evaluating patients with possible carpal tunnel syndrome. The selection of the best sensory testing protocol and use of motor conduction studies and needle electromyography are discussed. Interpretation requires care, particularly in light of the risks of false-positive testing results and possible technical errors.


Immunocytochemical localization of glial fibrillary acidic protein (GFAP) in the area postrema of the cat. Light and electron microscopic study.
Glial fibrillary acidic protein (GFAP) was demonstrated in the cytoplasm and processes of ependymal cells and astroglial components of the area postrema of the cat. These observations differ from the findings in the ependyma of the ventricular cavities which are consistently negative for the protein. Since some studies have suggested sensory functions of the glial cells in this emetic chemoreceptor trigger zone, a careful consideration of morphological and biochemical attributes of these cells seems appropriate.


Evaluation of inter-observer variability according to RECIST 1.1 and its influence on response classification in CT measurement of liver metastases.
The aim of this study is the evaluation of inter-observer variability in the measurement of liver metastases according to RECIST and its influence on response classification. A total of 100 radiologists measured liver target lesions, on pre- and post-chemotherapy CT scans of three patients. Each observer filled out a questionnaire about his personal and work features. The evaluations of a well experienced radiologist, considered as "the gold standard", were compared to those taken by the observers. The percentage of the observers in agreement with the reviewer, in terms of the response category and in terms of inter-observer variability, was calculated for each patient. The percentage of the inter-observer agreement was elevated. Most of the observers in agreement with the reviewer were senior radiologists, while those who disagreed were junior radiologist, but this result did not reach a statistical significance. More than 30% of observers disagreed with the reviewer at least in one of the three cases. RECIST measurements are reproducible on a large and heterogeneous population of radiologists. Age and expertise of the radiologist remain the most critical factors: this suggests a revision by well-experienced radiologists in clinical trials.


Anaesthesia for tracheal resection. Modified use of the Carden Tube.
Surgical procedures involving sharing of the airway between the anaesthetist and surgeon, such as bronchoscopy, microlaryngeal surgery and tracheal resection impose special problems on the anaesthetist. The surgeon requires unrestricted surgical access, whereas the anaesthetist must ensure adequate and safe pulmonary ventilation and anaesthesia. This case report describes a two stage technique for management of the airway and ventilation during tracheal resection for stenosis. Initially a modified Carden tube with a ventilating injector was used through a tracheostomy stoma and subsequently an orotracheal tube was substituted. Anaesthesia was maintained entirely by the inravenous route. The surgical access was unrestricted and there was no pulmonary contamination.


Worse Survival in Elderly Patients with Extremity Soft-Tissue Sarcoma.
Nearly half of soft-tissue sarcoma (STS) patients are over the age of 65, and the behavior of cancer in these elderly patients is poorly understood. The aim of this study was to assess the impact of age, sarcoma histotype, grade, stage, and treatment modalities on survival of extremity STS (ESTS) patients. Patients ≥18 years diagnosed with ESTS between 1989 and 2008 were selected from the Netherlands Cancer Registry. Survival rates and patient and treatment characteristics were analyzed for all patients. Relative survival and relative excess risk of death were estimated for young (<65 years) and older (>65 years) patients. Overall, 3066 patients were included in this study. Histotype was different between young (<65 years) and elderly (>65 years) patients (p < 0.001). Patients over the age of 65 were more often diagnosed with high-stage ESTS and an increasing proportion of high-grade ESTS (p < 0.001). The proportion of patients who received no treatment increased with age, and the elderly received fewer combined-modality treatments. Age was significantly associated with relative 5-year survival [72.7 % for younger patients and 43.8 % for the oldest elderly (>85 years)]. In multivariable analysis, age still remained a significant prognostic factor. Different distribution of sarcoma histotypes, more high-stage and high-grade sarcomas at diagnosis, less aggressive treatment, and worse survival rates emphasize the need for optimizing sarcoma research and care of the elderly.


Teamswork!
The physician-centric approach to patient care is giving way to a team-based model in which nurses, pharmacists, social workers and others truly share responsibility. The goal: Higher quality, enhanced efficiency.


Drinking behaviour in rats treated with isoprenaline, angiotensin II or angiotensin antagonists.
1. Isoprenaline hydrochloride injected subcutaneously in rats given a choice test of 1.8% NaCl and water, first induced saline intake which started immediately and was almost concluded in 15 min, followed by a copious water intake. When either saline or water were given in a separate test, saline intake surpassed the water intake in the first 15 min.2. The delay of 15, 30 or 60 min after injection of isoprenaline, 100 mug/kg, before drinking was allowed, significantly reduced saline intake but did not modify the amount of water subsequently drunk.3. Isoprenaline caused a sudden drop in arterial blood pressure, the extent and duration depending on the dose. The time of maximum drop 3-4 min after injection coincided with the time the rat drank salt.4. Isoprenaline-induced saline drinking was significantly reduced after bilateral nephrectomy but water intake was unaffected.5. The beta-adrenoceptor blocking agent, propranolol, inhibited isoprenaline-induced NaCl and water intake, while the alpha-adrenoceptor antagonist phenoxybenzamine abolished isoprenaline-induced NaCl intake and enhanced water intake.6. Saralasin acetate (P-113), a competitive inhibitor of angiotensin II, given into the third brain ventricle, prevented the isoprenaline-induced NaCl and water intake as well as angiotensin II-induced drinking. The angiotensin converting enzyme inhibitor SQ-20881 reduced the isoprenaline-induced NaCl and water intake.7. In conclusion, hypotension might be a component of salt drinking evoked by isoprenaline although the dipsogenic action of beta-stimulation is mainly due to endogenous renin-angiotensin activation.


Atherin: a newly identified, lesion-specific, LDL-binding protein in human atherosclerosis.
Prolonged retention of LDL in focal, atherosclerosis-prone areas of arteries is a primary event in atherogenesis. To determine whether unrecognized LDL-binding proteins participate in this process, we generated a cDNA expression library from deendothelialized rabbit aorta, a model for early atherosclerosis that shows striking focal LDL retention in healing lesions. Library screening identified a previously unknown, highly conserved, 56kDa LDL-binding protein that we call atherin. Confocal microscopy of human arteries shows that atherin is present only in atherosclerotic lesions, not in normal intima. Within lesions, atherin is found both in the extracellular compartment and within foam cells. Essentially all extracellular atherin, as well as atherin within foam cells, co-localizes with LDL across the entire spectrum of human disease, from early lesions to advanced plaques. Our results suggest that focal arterial LDL accumulation may be initiated and maintained by binding between LDL and atherin, and that atherin may play a central role in atherogenesis by immobilizing LDL in the arterial wall.


Ultrasound diagnosis of juvenile forearm fractures.
Metaphyseal forearm fractures are a common pathology in any emergency department. The standard diagnostic procedure is an X-ray of the forearm and wrist. Former studies have shown that these fractures can be visualized by ultrasound. The intention of this study was to evaluate the safety and reliability of the ultrasound diagnostic procedure in comparison with X-ray diagnosis. Patients aged 0-12 years with tentative diagnosis of forearm fracture in a physical examination were then examined, from six positions, with a 7.5-MHz linear array transducer. The diagnosis and the recommended treatment were noted, after which standard X-rays were taken. Finally, differences between diagnoses, the extent and direction of the deformity, and the treatment recommended after both diagnostic procedures were analysed. From January 2007 to May 2008, 93 patients were examined. We found 77 fractures in 64 patients (48 radius, 2 physeal fractures of the radius, 1 ulna, and 13 radius and ulna). The sensitivity of ultrasound in diagnosing forearm fractures was 94%, and the specificity was 99%. Difference between the means of the deformities were 1.6° (radius anterior-posterior direction), 1.6° (radius medial-lateral direction), 0.2° (ulna anterior-posterior direction), and 0.2° (ulna medial-lateral direction). Ultrasound seems to be a valuable and safe alternative to X-ray diagnosis.


Comparative study on prophylactic irradiation to the whole neck and to the upper neck for patients with neck lymph node-negative nasopharyngeal carcinoma.
The purpose of this study was to investigate the prophylactic irradiation volume to neck drainage areas for patients with N0 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). From January 2003 to October 2008, 270 patients with N0 classification (American Joint Committee on Cancer [AJCC] 2002 staging system) NPC who had undergone IMRT were retrospectively analyzed. Among all the patients, 171 patients received prophylactic upper-neck irradiation, and 99 patients received prophylactic whole-neck irradiation. At a median follow-up of 65.1 months (range, 4-106 months). The 5-year overall survival (OS), nodal recurrence-free survival (NRFS), and distant metastasis-free survival (DMFS) rates of the upper neck group and the whole neck group were 93.6% vs 90.9% (p = .553), 99.4% vs 99.0% (p = .278), and 98.8% vs 94.9% (p = .128), respectively. A total of 3 neck recurrences were found, including 2 from the whole neck group and 1 from the upper neck group. The latter (0.6%) was an out-of-field recurrence. Prophylactic irradiation to the upper neck (levels II, III, and VA) may be feasible for patients with neck lymph node-negative NPC.


Effects of NRA0045, a novel potent antagonist at dopamine D4, 5-HT2A, and alpha1 adrenaline receptors, and NRA0160, a selective D4 receptor antagonist, on phencyclidine-induced behavior and glutamate release in rats.
Administration of phencyclidine (PCP) to animals produces abnormal behavior such as hyperlocomotion, stereotyped behavior, and ataxia; this abnormal behavior is only weakly blocked by dopamine D(2) receptor antagonists. This study examined the effects of a novel thiazole derivative, NRA0045 which potently antagonizes not only dopamine D(4) receptors but also 5-HT(2A) and alpha(1) adrenaline receptors, and NRA0160, a selective dopamine D(4) receptor antagonist, on PCP-induced abnormal behavior, and accompanying increases in extracellular levels of glutamate in the medial prefrontal cortex. Furthermore, this study compared the effects of these drugs with those of clozapine and haloperidol. To study the effects of NRA-drugs, atypical and typical antipsychotics, we measured locomotor activity with an infra-red sensor, and stereotypy and ataxia on a rating scale. Extracellular glutamate levels were measured by in vivo microdialysis. NRA0045 (1 or 3 mg/kg) or clozapine (1 mg/kg) attenuated hyperlocomotion, stereotypy, and ataxia induced by PCP (7.5 mg/kg) without affecting behavior after saline injection. Although haloperidol (0.1 or 1 mg/kg) attenuated or inhibited PCP-induced behavior, this drug also affected behavior after saline injection. NRA0160 (0.1, 1, or 3 mg/kg) had no effect on behavior induced by PCP or saline. NRA0045 (3 mg/kg), but not NRA0160, inhibited PCP-induced increases in glutamate levels in the medial prefrontal cortex. PCP-induced hyperlocomotion correlated with the PCP-induced increases in glutamate levels in this brain region. These results suggest that the effects of NRA0045 on PCP-induced abnormal behavior are similar to those of the atypical antipsychotic clozapine. NRA0045 probably attenuates PCP-induced abnormal behavior by inhibiting the PCP-induced increase in glutamate levels in the medial prefrontal cortex; this inhibition may be mediated via the blockade of 5-HT(2A) receptors.


Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts.
Toxoplasma gondii is an obligate intracellular parasite infecting up to one third of the human population. The central event in the pathogenesis of toxoplasmosis is the conversion of tachyzoites into encysted bradyzoites. A novel approach to analyze the structure of in vivo-derived tissue cysts may be the increasingly used computational image analysis. The objective of this study was to quantify the geometrical complexity of T. gondii cysts by morphological, particle, and fractal analysis, as well as to determine if it is impacted by parasite strain, cyst age, and host type. A total of 31 images of T. gondii brain cysts of four type-2 strains (Me49, and local isolates BGD1, BGD14, and BGD26) was analyzed using ImageJ software. The parameters of interest included diameter, circularity, packing density (PD), fractal dimension (FD), and lacunarity. Although cyst diameter varied widely, its negative correlation with PD was observed. Circularity was remarkably close to 1, indicating a perfectly round shape of the cysts. PD and FD did not vary among cysts of different strains, age, and derived from mice of different genetic background. Conversely, lacunarity, which is a measure of heterogeneity, was significantly lower for BGD1 strain vs. all other strains, and higher for Me49 vs. BGD14 and BGD26, but did not differ among Me49 cysts of different age, or those derived from genetically different mice. The results indicate a highly uniform structure and occupancy of the different T. gondii tissue cysts. This study furthers the use of image analysis in describing the structural complexity of T. gondii cyst morphology, and presents the first application of fractal analysis for this purpose. The presented results show that use of a freely available software is a cost-effective approach to advance automated image scoring for T. gondii cysts.


[Olfactory disorders].
In contrast to what the medical community thought, human olfaction is far more functional and performing than previously believed. Almost fifteen percent of the general population is concerned by an olfactory disorder. The causes of olfactory dysfunction are numerous and in certain cases olfactory alteration precedes neurodegenerative or systemic diseases. Thus, a thorough workup consisting of an otolaryngological examination, olfactory testing and if necessary further exams is emphasized. Since medical knowledge on olfactory dysfunction is only emerging, curative treatments are not always available. In contrast to other neurons, olfactory neurons have the capacity of spontaneous regeneration and a large part of the physician's job is to inform and follow-up patients with olfactory disorders.


Camptodactyly Caused by an Anomalous Origin of the Flexor Digitorum Superficialis Tendon: A Case Report and Review of the Literature.
Camptodactyly is a flexion contracture of the proximal interphalangeal joints and is known as an isolated malformation that affects 1 in 300 in the population and can be inherited as an autosomal dominant trait with variable expression. A 17-year-old female was referred to the Clinic of Plastic Surgery, University Clinical Center of Kosovo, Prishtina, for the first time with camptodactyly of the little finger in the right hand. She was presented with a progressive flexion contracture of the proximal interphalangeal joint greater than 110 degrees of her right little finger. According to our observations from outpatient consultations, we concluded that the case of camptodactyly in the little finger in the flexible form (>110 degrees), which underwent surgical treatment, presented excellent result. Therefore, we think that the surgical technique used in our case report will contribute to treating this complicated deformity.


Serum indoxyl sulfate as a potential biomarker of aortic arterial stiffness in coronary artery disease.
Indoxyl sulfate (IS), a dietary tryptophan metabolite, acts as a cardiotoxin and uremic toxin. High IS levels are associated with chronic kidney disease and cardiovascular diseases. This study investigated the association between serum IS levels and aortic arterial stiffness (AAS) in coronary artery disease (CAD) patients. The carotid-femoral pulse wave velocity (cfPWV) was measured by the SphygmoCor system and patients with values of >10 m/s were classified in the AAS group. The baseline characteristics were recorded and measured (including biochemical and clinical data). Serum IS levels were determined using liquid chromatography-mass spectrometry. AAS occurred in 50 (34.7%) of 144 patients with CAD. They were older, had higher IS levels and percentages of diabetes, systolic blood pressure, blood urea nitrogen, and creatinine but lower estimated glomerular filtration rates. The IS level and older age significantly correlated with AAS [odds ratio (OR) = 3.834, p = 0.031; OR = 1.095, p = 0.002, respectively]. Furthermore, the serum IS level (β = 0.167, adjusted R2 change: 0.026, p = 0.027) had a significant positive correlation with cfPWV. Taken together, higher serum IS levels are potential independent biomarkers for AAS in patients with CAD. Therefore, early checking of serum IS levels may help prevent CAD progression and have clinical implications in the near future.


NaBiS2 decorated polysaccharide sponges for adsorption-photocatalytic degradation of dye under visible light illumination.
Dye is emissions aggravating aquatic ecosystem pollution, and photocatalysis is considered the most appealing option to remove dyes by degradation. However, the current photocatalysts suffer from agglomeration, large bandgaps, high mass transfer resistance, and high operation cost. Herein, we present a facile hydrothermally induced phase separation and in situ synthesis strategy for fabrication of sodium bismuth sulfide (NaBiS2)-decorated chitosan/cellulose sponges (NaBiCCSs). The NaBiCCSs demonstrate unique polysaccharide cellular structure (150-500 μm), uniformly immobilized NaBiS2 nanoparticles (70-90 nm), narrow bandgap (1.18 eV), high photocurrent (0.74 μA/cm2), and outstanding compressibility. Benefiting from the characteristics and the high affinity to dyes, the NaBiCCSs provide innovative synergistic adsorption-photocatalytic degradation model for dye removal, attaining a superior methylene blue removal rate of 98.38 % under visible light illumination and offering good reusability. This study offers a sustainable technical solution for dye contaminant removal.


Innovative screening for functional improved aromatic amine derivatives: Toxicokinetics, free radical oxidation pathway and carcinogenic adverse outcome pathway.
Aromatic amines, one of the most widely used low-cost antioxidants in rubbers, have been regarded as pollutants with human health concerns. To overcome this problem, this study developed a systematic molecular design, screening, and performance evaluation method to design functionally improved, environmentally friendly and synthesizable aromatic amine alternatives for the first time. Nine of 33 designed aromatic amine derivatives have improved antioxidant property (lower bond dissociation energy of N-H), and their environmental and bladder carcinogenicity impacts were evaluated through toxicokinetic model and molecular dynamics simulation. The environmental fate of the designed AAs-11-8, AAs-11-16, and AAs-12-2 after antioxidation (i.e., peroxyl radicals (ROO·), hydroxyl radicals (HO·), superoxide anion radicals (O2·-) and ozonation reaction) was also analyzed. Results showed that the by-products of AAs-11-8 and AAs-12-2 have less toxicity after antioxidation. In addition, human bladder carcinogenicity of the screened alternatives was also evaluated through adverse outcome pathway. The carcinogenic mechanisms were analyzed and verified through amino acid residue distribution characteristics, 3D-QSAR and 2D-QSAR models. AAs-12-2, with high antioxidation property, low environmental impacts and carcinogenicity, was screened as the optimum alternative for 3,5-Dimethylbenzenamine. This study provided theoretical support for designing environmentally friendly and functionally improved aromatic amine alternatives from toxicity evaluation and mechanism analysis.


Infarction of accessory spleen.
A rare disease that can mimic acute appendicitis is infarction of accessory spleen. It may occur in children and is difficult to diagnose preoperatively. Greater awareness of this entity may show not only that it is associated with other intraabdominal anomalies but also that it is more common in the tropics than elsewhere. Two cases are reported.


Comparison of different approaches for dose response analysis.
Characterizing an appropriate dose-response relationship and identifying the right dose in a clinical trial are two main goals of early drug-development. MCP-Mod is one of the pioneer approaches developed within the last 10 years that combines the modeling techniques with multiple comparison procedures to address the above goals in clinical drug development. The MCP-Mod approach begins with a set of potential dose-response models, tests for a significant dose-response effect (proof of concept, PoC) using multiple linear contrasts tests and selects the "best" model among those with a significant contrast test. A disadvantage of the method is that the parameter values of the candidate models need to be fixed a priori for the contrasts tests. This may lead to a loss in power and unreliable model selection. For this reason, several variations of the MCP-Mod approach and a hierarchical model selection approach have been suggested where the parameter values need not be fixed in the proof of concept testing step and can be estimated after the model selection step. This paper provides a numerical comparison of the different MCP-Mod variants and the hierarchical model selection approach with regard to their ability of detecting the dose-response trend, their potential to select the correct model and their accuracy in estimating the dose response shape and minimum effective dose. Additionally, as one of the approaches is based on two-sided model comparisons only, we make it more consistent with the common goals of a PoC study, by extending it to one-sided comparisons between the constant and alternative candidate models in the proof of concept step.


Accumulation of allo-MHC cross-reactive memory T cells in bone marrow.
The T cells in the bone marrow (BM) have recently been shown to be enriched with memory T cells. We investigated in this study the reactivity of minor-antigen specific memory cytotoxic T lymphocytes (CTLs) induced from the BM of in vivo primed mice using two different antigen systems. The antigen-specific CTLs could be efficiently induced from the BM of immunized mice. This CTL activity was not observed with naïve control mice, indicating that the activity was largely attributable to the memory T cells. Notably, these minor antigen specific CTLs showed cross-reactivity to allo-MHC antigens. Cold target inhibition analyses revealed that the same CTL populations were responsible for both anti-minor antigen and anti-allo-MHC reactivity. Taken collectively, these results not only confirmed functionally the enrichment of memory CTLs in the BM, but also indicated that such memory cells could cross-react with allo-MHC antigens. The possible role of these BM-resident memory T cells in the development of graft-versus-host disease (GVHD) is also discussed.


Prognosis of resected invasive mucinous adenocarcinoma compared with the IASLC histologic grading system for invasive nonmucinous adenocarcinoma: Surgical database study in the TKIs era in Korea.
The prognosis of invasive mucinous adenocarcinoma (IMA) remains controversial and should be clarified by comparison with the International Association for the Study of Lung Cancer (IASLC) histologic grading system for invasive nonmucinous adenocarcinoma (INMA). This study included patients with IMA who underwent curative resection. Their clinicopathological outcomes were compared with those of patients with INMA. Propensity score matching was performed to compare the prognosis of IMA with IASLC grade 2 or 3. Kaplan-Meier survival curves and log-rank tests were used to analyze recurrence-free survival (RFS) and overall survival (OS). The prognoses of IMA and IASLC grade 2 were similar in terms of RFS and OS. Although patients with IMA had better RFS than patients with IASLC grade 3, the OS was not significantly different. After propensity score matching, IMA demonstrated similar RFS to IASLC grade 2 but superior to IASLC grade 3; there was no difference in the OS compared with grades 2/3. Multivariate analysis revealed that tumor size (hazard ratio [HR] = 1.20, p = 0.028), lymphovascular invasion (HR = 127.5, p = 0.003), and maximum standardized uptake value (HR = 1.24, p = 0.005) were poor prognostic predictors for RFS. Patients with IMA demonstrated RFS similar to and significantly better than that of patients with IASLC grades 2 and 3, respectively. For OS, IMA prognosis was between that of IASLC grades 2 and 3. Since the prognosis of IMA among lung adenocarcinomas appears to be relatively worse, further clinical studies investigating IMA-specific treatment and follow-up plans are necessary to draw more inferences.


[Association coefficients of three planktonic rotifer species in the field and their explanation by interspecific relationships (competition, predator-prey relationships)].
Coefficients of interspecific association of three rotifer species (Brachionus calyciflorus, Brachionus rubens, Asplanchna brightuelli) of 314 plankton samples from about 100 ponds in South Germany were determined: two coefficients basing on present-absent data (Table 2: C 7, C 8), one coefficient regarding population density (Table 2: C 9), and one coefficient of partial interspecific association taking in mind the presence or absence of the third species (Table 3: C p). Some of the computed coefficients are significantly positive or negative indicating that joint appearances are sometimes more and sometimes less frequent than expected by chance. Most of these results cam be interpreted by the knowledge of interspecific relationships, vz. competition between Brachionus calyciflorus and B. rubens, and predator-prey relationships between Asplanchna brightwelli and B. rubens which had been detected in former studies. In each case the association between two of the species is modified by the presence of the third. The causes (alternative prey, destruction of the competitors etc.) are discussed.


Serum ferritin as a marker of potential biochemical iron overload in athletes.
Beyond hematological manipulation, iron supplementation therapy is commonplace in athletes to counterbalance physiological or pathologic anemia and to prevent physiologic dysfunction. However, misuse of iron therapy, occasionally resulting in iron overload, is not free from metabolic risks. We planned to measure baseline serum ferritin concentration in sedentary individual and athletes. The Institute of Clinical Biochemistry of the Verona University. PARTICIPANTS Serum ferritin was measured in 60 male healthy sedentary controls, 80 amateur road cyclists, 42 male professional cross-country skiers, and 88 professional male road cyclists. The biochemical iron overload was ascertained by measuring baseline serum ferritin concentration as a reliable approach that mirrors the total body iron content. The concentration of serum ferritin in healthy controls was 112 +/- 78 ng/mL, whereas that of amateur cyclists, professional skiers, and professional cyclists was 127 +/- 76 ng/mL (P = 0.185), 183 +/- 130 ng/mL (P = 0.001), and 332 +/- 218 ng/mL (P < 0.001), respectively. Both categories of professional athletes showed significantly increased concentrations of serum ferritin, whereas the concentration of amateur cyclists was comparable to that of healthy sedentary controls. Professional endurance athletes have serum ferritin concentrations that are 2-fold to 3-fold higher than those of matched sedentary individuals and amateur athletes, exceeding the threshold for the diagnosis of biochemical iron overload and unveiling potential metabolic risks.


Work-Function-Tunable Electron Transport Layer of Molecule-Capped Metal Oxide for a High-Efficiency and Stable p-i-n Perovskite Solar Cell.
The composite electron transporting layer (ETL) of metal oxide with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) prevents perovskite from metal electrode erosion and increases p-i-n perovskite solar cell (PVSC) stability. Although the oxide exhibits protective function, an additional work function modifier is still needed for good device performance. Usually, complicated multistep synthesis is employed to have a highly crystalline film that increases manufacturing cost and inhibits scalability. We report a facile synthesis of a novel organic-molecule-capped metal oxide nanoparticle film for the composite ETL. The nanoparticle film not only has a dual function of electron transport and protection but also exhibits work function tunability. Solvothermal-prepared SnO2 nanoparticles are capped with tetrabutylammonium hydroxide (TBAOH) through ligand exchange. The resulting TBAOH-SnO2 nanoparticles disperse well in ethanol and form a uniform film on PCBM. The power conversion efficiency of the device dramatically increases from 14.91 to 18.77% using this layer because of reduced charge accumulation and aligned band structure. The PVSC thermal stability is significantly enhanced by adopting this layer, which prevents migration of I- and Ag. The ligand exchange method extends to other metal oxides, such as TiO2, ITO, and CeO2, demonstrating its broad applicability. These results provide a cornerstone for large-scale manufacture of high-performance and stable PVSCs.


Arterial kink and damage in normal segments of the superficial femoral and popliteal arteries abutting nitinol stents--a common cause of late occlusion and restenosis? A single-center experience.
To identify a new angiographic parameter associated with poor short- and long-term outcomes with nitinol stenting in the larger infrainguinal arteries. Nitinol stents have proven to be useful and safe, but imperfect, tools for treating claudication and limb-threatening ischemia. Primary and secondary patency in superficial femoral artery (SFA) occlusions treated with nitinol stents are up to 80% at 1 year, but restenosis is between 40-50% at 2 years. The causes of SFA and popliteal restenosis remain unclear. Stent fracture has been implicated in some cases of restenosis, but this is clearly the minority. Chronic mechanical trauma to the arteries caused by native vessel-stent interaction, intensified by limb motion over time, appears to be a more plausible explanation. Presented here are 2 cases of restenosis apparently caused by acute and chronic trauma to the native vessel from interaction of the artery with the ends of relatively rigid nitinol stent systems. The source of some future restenotic and occlusive events are not apparent using routine angiography techniques. The additional step of an on-table leg bend test at 80-90 degrees will allow the interventionalist to visualize many cases of negative interaction between the native artery and the stents that will occur during routine movement. This allows the operator to potentially avoid stent-induced arterial trauma.


Membrane proteomic analysis identifies the polarity protein PARD3 as a novel antiviral protein against PEDV infection.
Porcine epidemic diarrhea virus (PEDV) is a highly pathogenic enteric coronavirus causing lethal watery diarrhea in suckling piglets. PEDV could remodel host membrane structures for their replication, assembly and escape from host cells. However, little is known about the host membrane proteins of PEDV infection. In this study, we analyzed differentially abundant proteins (DAPs) between PEDV infection group and control group and identified the polarity protein PARD3 as one of the most significantly DAPs. PARD3 is implicated in the formation of tight junctions at epithelial cell-cell contacts. Then, we found that PEDV infection promoted the degradation of PARD3 via the ubiquitin proteasome pathway. Moreover, knockdown of PARD3 promoted the proliferation of PEDV. Further study showed that the downregulation of PARD3 altered the normal morphology of the tight junction proteins and promoted apical and basolateral virus proliferation. Tight junctions enable epithelial cells to form physical barriers, which act as an innate immune mechanism that can impede viral infection and PEDV affected the barrier functions by causing degradation of PARD3. Taken together, this work is the first time to investigate the membrane protein profile of PEDV-infected cells using quantitative proteomics and suggests that PARD3 could be a potential novel antiviral protein against PEDV infection. SIGNIFICANCE: Membrane proteins are involved in various physiological and biochemical functions critical for cellular function. It is also dynamic in nature, where many proteins are changed during in response to environmental stress. However, membrane proteins are difficult to study because of their hydrophobicity. Membrane proteomic methods using mass spectrometry analysis have been developed and applied for the characterization of the plasma membrane and subcellular organelles of various virus infected cells. Porcine epidemic diarrhea virus (PEDV) is an enteric pathogen of importance to the swine industry, causing high mortality in neonatal piglets. Because PEDV infected Vero cells can lead to significant changes in cell membrane morphology and form syncytial lesions. Here, we isolated the membrane proteins of PEDV infected and control cells and applied isobaric tags for relative and absolute quantification (iTRAQ) labeling coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantitatively identify the differentially abundant proteins (DAPs) in PEDV-infected Vero cells and confirmed the DAPs by performing RT-qPCR and Western blot analysis. Among these differential proteins, we focused on a down-regulated protein PARD3 which is important for cell tight junction and cell polarity. Loss of PARD3 can destroy the tight junction of cells and promote the proliferation of PEDV in the apical and basolateral sides. These findings will provide valuable information to better understand the mechanisms underlying the host defense responses to PEDV infection.


Self-management strategies in chronic obstructive pulmonary disease.
This article enables the reader to understand the newest scientific concepts and advances in the field of self-management in chronic obstructive pulmonary disease, recognize the importance of self-management education and what might be needed to enhance behavior modification, and translate these advances into strategies and specific interventions in clinical practice.


Clinical research in psychopharmacology, the current situation and its perspectives. A conversation with Pierre-Michel Llorca.
For this issue, Luc Zimmer, professor of pharmacology and chair of the Neuropsychopharmacology Committee of the French Society of Pharmacology and Therapeutics (SFPT), talked with Michel Llorca, professor of psychiatry at the Université d'Auvergne and head of a department of psychiatry at the University Hospital of Clermond-Ferrand. They discuss together the positioning of psychiatry in the neurosciences and the need to build bridges with other medical disciplines. Through examples and professional experiences, they also talk about the difficulties of developing clinical biomarkers for psychiatry and ultimately for psychopharmacology. Finally, they discuss the current difficulties facing research of drugs for psychiatry, pointing out some success stories.


Acute effects of decreased glutamine supply on protein and amino acid metabolism in hepatic tissue: a study using isolated perfused rat liver.
Glutamine deficiency, a common finding in severe illness, has a negative influence on immune status, protein metabolism, and disease outcome. In several studies, a close relationship between glutamine, branched-chain amino acid (BCAA), and protein metabolism was demonstrated. The aim of the present study was to investigate the effect of glutamine deficiency on amino acid and protein metabolism in hepatic tissue using a model of isolated perfused rat liver (IPRL). Parameters of protein metabolism and amino acid metabolism were measured using both recirculation and single pass technique with L-[1-(14)C]leucine and [1-(14)C]ketoisocaproate (KIC) as a tracer. Glutamine concentration in perfusion solution was 0.5 mmol/L in control and 0 mmol/L in the glutamine-deficient group. The net release of glutamine (about 11 micromol/g/h) and higher net uptake of most of the amino acids was observed in the glutamine-deficient group. There was an insignificant effect of lack of glutamine on hepatic protein synthesis, proteolysis, and the release of urea. However, significantly lower release of proteins by the liver perfused with glutamine-deficient solution was observed. The lack of glutamine in perfusion solution caused a significant decrease in leucine oxidation (6.66 +/- 1.04 v 13.67 +/- 2.38, micromol/g dry liver/h, P <.05) and an increase in KIC oxidation (163.7 +/- 16.5 v 92.0 +/- 12.9 micromL/g dry liver/h, P <.05). We conclude that decreased delivery of glutamine to hepatic tissue activates glutamine synthesis, decreases resynthesis of essential BCAA from branched-chain keto acids (BCKA), increases catabolism of BCKA, and has an insignificant effect on protein turnover in hepatic tissue.


An increase in the expression of neuropeptidergic vasodilator, but not vasoconstrictor, cerebrovascular nerves in aging rats.
Perivascular nerve fibres containing noradrenaline (NA), serotonin (5-HT), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) and calcitonin gene-related peptide (CGRP) were localized in whole-mount stretch preparations of the arteries of the rat circle of Willis using fluorescence and immunohistochemical techniques. Changes in the pattern and density of these perivascular nerves were studied from birth to 27 months of age. All perivascular nerve types reached a peak density of innervation at 1 month of age. This was followed by a general fall in the density of fluorescent nerve fibres. However, with aging, there was a decrease in the expression of vasoconstrictor neurotransmitters (NA and 5-HT) in cerebrovascular nerves, whereas the expression of vasodilator neurotransmitter (VIP and CGRP) in perivascular nerve fibres supplying the rat cerebral arteries was strikingly increased in old age. The density of NPY- and SP-containing nerve fibres was not significantly altered in old age. These changes are discussed in relation to the increased incidence of cerebrovascular disorders in the elderly.


Two-component protein adsorption kinetics in porous ion exchange media.
This work provides a theoretical analysis of multicomponent adsorption kinetics for conditions typical of protein adsorption in porous ion exchangers as well as experimental results for the adsorption of lysozyme/cytochrome c mixtures in the cation exchanger SP-Sepharose-FF. The theory predicts the formation of overshoots in the intraparticle concentration profiles and in the total amount adsorbed for the more weakly adsorbed component. An analytical solution valid for the case where the isotherms are rectangular is developed and found to be in good agreement with the limiting behavior of the general numerical solution of the model equations. The experimental results show that the two proteins are competitively adsorbed and that an overshoot of adsorbed cytochrome c occurs during simultaneous adsorption. Model predictions based on the assumption that the adsorption isotherms are rectangular and that lysozyme completely displaces cytochrome c are in qualitative and quantitative agreement with the experimental kinetics suggesting that the overshoot phenomena observed with multicomponent systems in these resins can be explained with a diffusion model without the need to account for flux coupling or electrophoretic contributions to transport.


Validation of specific questionnaires to assess nausea and vomiting of pregnancy in a French population.
To validate the modified Pregnancy-Unique Quantification of Emesis and Nausea (PUQE) score and the Health-Related Quality of Life for Nausea and Vomiting of Pregnancy (NVP-QOL) score in a French population. A retrospective study was conducted of data for women who delivered at a tertiary care hospital in La Roche sur Yon, France, between November 1, 2012, and April 1, 2013. Only women who reported nausea and vomiting of pregnancy (NVP) in the first trimester were invited to respond to the two questionnaires. Overall, complete questionnaires were available from 399 women, 238 (59.6%) of whom reported NVP in the first trimester. The modified-PUQE score was associated with the self-reported symptom severity (P<0.001). A relationship was also noted when either the NVP-QOL score or the modified-PUQE score was compared with the symptom intensity (P<0.001 for both comparisons). Furthermore, a high NVP-QOL score was associated with a high modified-PUQE score (P<0.001). The modified-PUQE and NVP-QOL scores provided valid indices for assessing NVP severity and alterations in quality of life. Owing to its simplicity, the modified-PUQE score might be used routinely among women experiencing NVP in the first trimester of pregnancy.


Thymus-independent T-cell differentiation in vitro.
The generation of large quantities of novel human T-cell clones ex vivo would make a wide range of gene- and immuno-therapies for tumours and viral infections possible. Several techniques have been described to generate, in vitro and in vivo (using xenogenic hosts), mature T cells from fetal-neonatal and adult human CD34+ cells. All these techniques are cumbersome and cannot be easily translated into clinical protocols because they involve co-cultivation of CD34+ cells with thymic fragments from either human or murine fetuses. We report that the mononuclear cells of human cord blood contain a cell population that supports the differentiation of CD34+ cells into CD4+ or CD8+ naive T cells in serum-deprived cultures stimulated with stem cell factor and interleukin 7. CD4+ or CD8+ CD45RA+ TCRalphabeta+ T cells were continuously produced in vitro over a period of 20 d under these conditions. The generation of T cells in these cultures was a dynamic process and clones of T cells expressing new T-cell receptor beta-chain rearrangements were generated over time. These results pave the way for the development of very simple culture conditions for ex-vivo production of naive helper or cytotoxic T cells which could be very useful for gene- and immuno-therapy of human diseases.


Identification and functional characterization of three myeloid differentiation factor 88 (MyD88) isoforms from thick shell mussel Mytilus coruscus.
Myeloid differentiation factor 88 (MyD88) is a pivotal adapter protein that involved in interleukin-1 receptor/toll-like receptor (IL-1R/TLR) signal transduction, which could spur downstream cascades and eventually drawn into innate immune response. MyD88 has been extensively studied in vertebrates, however, the information ascribe to MyD88 in invertebrates is still very scarce especially its function annotation remains extremely obscure. At here, three novel MyD88 isoforms termed McMyD88a, McMyD88b and McMyD88c were firstly cloned from thick shell mussel Mytilus coruscus. McMyD88a, McMyD88b and McMyD88c shared domain topology containing the Death domain (DD) and TIR domain (TIR) with its counterparts in mammals. All three McMyD88s were ubiquitously expressed in examined tissues in thick shell mussel, with the higher expression levels in immune-related tissues such as haemocytes, gills and digestive glands. Upon Vibrio alginolyticus, polyinosine-polycytidylic acid (poly I:C) and lipopolysaccharide (LPS) challenge, McMyD88a, McMyD88b and McMyD88c transcripts were significantly induced in haemocytes despite of differential expression levels and responsive time points. Overexpression of McMyD88a, McMyD88b and McMyD88c showed a dose-dependent induction to NF-κB or ISRE in mammalian cell lines. Taken together, these results suggested that McMyD88a, McMyD88b and McMyD88c are members of MyD88 family and play potential roles in innate immune response to pathogenic invasions in thick shell mussel. Moreover, these results suggested indirectly the existence of a MyD88-dependent signaling pathway in thick shell mussel, and provide insight into the immunoregulatory effect in molluscs.


Seizures induced by microperfusion of glutamate and glycine in the hippocampus of rats pretreated with latrunculin A.
Changes in the membrane distribution of N-methyl-D-aspartate (NMDA) glutamate receptors seem to produce dramatic modifications in neuronal excitability and other properties of the neuron. In order to determine in vivo if these effects are due to the binding of extracellular glutamate and glycine to NMDA extrasynaptic receptors, we perfused the hippocampus of freely moving rats with the actin depolymerizant agent latrunculin A (4 microM) through microdialysis probes. One month later, continuous microperfusion of glutamate (1 mM) or glycine (1 mM) was used to induce epileptic seizures in the animals pretreated with latrunculin A. Glutamate microperfusion induced seizures in 50% of the animals studied, and glycine induced seizures in 75% of the rats. However, no effect was observed on control rats, or on those animals previously treated with picrotoxin. Simultaneous microperfusion of 100 microM MK-801 significantly reduced the number and duration of seizures induced by both glutamate and glycine. This study demonstrates that the application of latrunculin A results in long-term changes in susceptibility to the epileptogenic action of glutamate and glycine.


Visual Conformity With Affirmed Gender or "Passing": Its Distribution and Association With Depression and Anxiety in a Cohort of Transgender People.
Visual conformity with affirmed gender (VCAG) or "passing" is thought to be an important, but poorly understood, determinant of well-being in transgender people. VCAG is a subjective measure that is different from having an inner sense of being congruent with one's gender identity. We examined the frequency and determinants of VCAG and explored its association with mental health outcomes in a cohort of transgender adults. The "Study of Transition, Outcomes & Gender (STRONG)" is a cohort of transgender individuals recruited from 3 Kaiser Permanente health plans located in Georgia, Northern California and Southern California. A subset of cohort members completed a survey between 2015 and 2017. VCAG was assessed as the difference between 2 scales: scale 1 reflecting the person's sense of how they are perceived by others, and scale 2 reflecting the person's desire to be perceived. Participants were considered to have achieved VCAG when their scale 1 scores were equal to or exceeded their scale 2 scores. The frequency of VCAG and their independent associations with anxiety and depression symptoms were explored using data from 620 survey respondents including 309 transwomen and 311 transmen. Based on self-described gender identity, none of the participants identified as nonbinary or gender fluid. VCAG, depression, and anxiety. VCAG was achieved in 28% of transwomen and 62% of transmen and was more common in persons who reported greater sense of acceptance and pride in their gender identity as measured on the Transgender Congruence Scale. Another factor associated with greater likelihood of VCAG was receipt of gender-affirming surgery, but the association was only evident among transmen. Participants who achieved VCAG had a lower likelihood of depression and anxiety with prevalence ratios (95% confidence intervals) of 0.79 (0.65, 0.96) and 0.67 (0.46, 0.98), respectively. VCAG may serve as an important outcome measure after gender-affirming therapy. Strengths of this study include a well-defined sampling frame and use of a novel patient-centered outcome of interest. Cross-sectional design and uncertain generalizability of results are the limitations. These results, once confirmed by prospective studies, may help better characterize the determinants of well-being in the transgender community, facilitating the design of interventions to improve the well-being and quality of life of this vulnerable population. To M, Zhang Q, Bradlyn A, et al. Visual Conformity With Affirmed Gender or "Passing": Its Distribution and Association With Depression and Anxiety in a Cohort of Transgender People. J Sex Med 2020;17:2084-2092.


A new understanding: Gene expression, cell characteristic and antioxidant enzymes of Zygosaccharomyces rouxii under the D-fructose regulation.
Zygosaccharomyces rouxii is a well-known salt-tolerant yeast. In our previous study, it was interesting that Z. rouxii could produce higher levels of 4-hydroxy-2, 5-dimethyl-3(2 H)-furanone in 120 g/L D-fructose and 180 g/L NaCl involved YPD medium at 5 d. In order to explore the resistance and furanone production mechanisms of Z. rouxii under D-fructose regulation, a comparative transcriptomics method in Z. rouxii was to set to find differentially expressed genes, the physiological and biochemical indexes (growth and cell morphology, lipid peroxidation and relative electrical conductivity, the antioxidant enzymes activity), and the expression of oxidoreductase activity genes. The results indicated that a larger number of different expressed genes at transcriptome analysis, such as the series antioxidant enzymes were related to the resistance characteristics. Research had confirmed that the living cell numbers and cell areas of D-fructose regulation group were significantly lower than the controls at the initial stage, while those higher than of the controls at the late stage. During the fermentation period, the lipid peroxidation and the relative electrical conductivity of the yeast cell membrane were increased. And also the D-fructose regulation group present lower inhibition superoxide anion ability. The activity of CAT in the D-fructose regulation group was always higher than that of the control group. Only the activity of GSH-Px was found to be significantly increased at 1 d except for other enzymes activities. Most of the oxidoreductase activity genes, such as especially the GSH-Px gene under D-fructose regulation conditions were expressed at higher levels than those of control groups. Combining the levels of transcription and enzymes activity data, those could understand that exogenous D-fructose had a stress effect on Z. rouxii at the early stage of culture. With the fermentation time progress, it was no longer a stressor substance for the Z. rouxii, and changed the nutrient to promote growth of Z. rouxii in the later stages. During the whole process, GSH-Px was the main defense enzyme and CAT was the sustained defense enzyme. Therefore, the experimental results might provide effective mechanisms in Z. rouxii for practical application of furanone production in the industry under exogenous D-fructose regulation.


Flood syndrome managed by partial splenic embolization and percutaneous peritoneal drainage.
Flood syndrome is a rare complication of cirrhosis of liver accompanied by ascites and a sudden rupture of umbilical hernia causing drainage of ascitic fluid from abdominal cavity. We report management of a case of Flood syndrome which was caused by rupture of incisional hernia. The clinical picture was similar to well described and widely accepted Flood syndrome. A 70-year-old female with decompensated hepatitis C cirrhosis was transported to the emergency department with a sudden drainage of ascitic fluid after sudden dehiscence of pre-existing incisional hernia and diffuse abdominal tenderness. Initially, she was managed by applying ostomy bag and diuretics to reduce the ascites. On 8th day of admission, a 16 Fr. drain was percutaneously placed in the left lower abdominal quadrant to divert the fluid from the abdominal wall defect. On 13th day, 80% partial splenic embolization (PSE) was attempted to control portal hypertension to reduce the ascites volume. After PSE, the hepatic venous pressure gradient reduced from 28 to 21cm H2O. The peritoneal drain was removed on 16th day and she was discharged on 22nd day. We conclude that PSE and temporary percutaneous peritoneal drainage are useful option to manage Flood syndrome.


Elongation of the murein sacculus of Escherichia coli.
Elongation is an orderly multisite process in which, at each of about 90 growth points, two strands of murein are concurrently being synthesized, inserted and cross-linked to the sacculus. The enzymes involved move around the circumference of the cytoplasmic membrane at a rate of about 5 nm per second as new strands are being inserted, and this rate is sufficient to double the length of the cell during the cell division cycle.


Review: the sickle hemoglobinopathies--genetic analyses of common phenocopies and new molecular approaches to treatment.
Within the very large group of sickle cell hemoglobinopathies several phenocopy clusters exist. These can be conveniently classified as: 1) conditions in which HbA and S are present, 2) disorders where HbS is the predominant hemoglobin, and 3) the HbSF phenotype. This review will focus on distinguishing the genotype of these common phenocopies as well as new potential approaches to therapy.


Factors limiting the commercial application of animal cells in culture.
The application of quality control and assurance procedures to the components of animal cell cultures has transformed what was an art to a viable industrial technology. This results in the successful large scale operation of such cultures. However it is clear that the cost of obtaining a license to produce materials from animal cells in culture severely impedes the movement of products into the market place. It is therefore necessary to examine in more detail the reasons for the reluctance of the regulatory authorities to issue product licences and in particular to appreciate the way ethical issues influence this process. This paper reviews these issues and indicates a way ahead.


Notch and BCR signaling synergistically promote the proliferation of Raji B-lymphoma cells.
The evolutionarily conserved Notch signaling pathway plays a pivotal role in cell proliferation, apoptosis, and cell fate decision from invertebrates to vertebrates, and is oncogenic in some human hematopoietic malignancies. To study the role of Notch signaling in B-lymphoma, we expressed a soluble fragment of human Delta-like1 (hDll1) in E. coli, which was shown to activate the Notch signaling. Incubation of Burkitt's lymphoma Raji cells with the soluble hDll1 led to gamma-secretase-dependent up-regulation of a Notch downstream gene, Hes1. This treatment synergized with B-cell receptor (BCR)-mediated signaling to promote proliferation of Raji cells in vitro, which was cancelled by GSI. We further showed that Notch signaling significantly repressed, while gamma-secretase inhibitor (GSI) enhanced, "natural" apoptosis of Raji cells. Because c-myc is a downstream gene of both Notch signaling and BCR signaling, and GSI blocked c-myc expression in the presence of hDll1 and anti-IgM, Notch signaling might interact with BCR signaling at the level of c-myc expression to regulate proliferation and apoptosis of B-lymphoma cells.


Effect of HLA-compatibility in married couples on the development and severity of gestosis.
We studied the effect of histocompatibility in married couples on the development and severity of gestosis. It was found that gestosis more often develops in women with two common HLA alleles of class II major histocompatibility complex with her husband. The greatest number of coincidences was detected in subgroups with medium and severe gestosis. Perinatal outcomes in women with medium-severe gestosis having HLA-alleles common with husbands are characterized by delivery of babies with lower body weight.


Adrenal dopamine content of the developing rat. Influence of the thyroid status and insulin-hypoglycaemia.
Neonatal hypothyroidism accelerates the postnatal evolution of the adrenal dopamine (DA) content and concentration in the young rat. In 14-day-old control animals, insulin-hypoglycaemia leads to a transient increase in adrenal dopamine content up to 159% above the value in saline-injected animals. This increase is already at its maximum 1 h after insulin administration and lasts 7 h. In the hypothyroid animals, the DA increase evoked by hypoglycaemia is impaired in magnitude (74%) and duration (4 h).


Early administration of FTY720 prevents chronic airway as well as vascular destruction in experimental rat lung transplantation.
Chronic rejection (CR) in terms of bronchiolitis obliterans (BO) and vascular sclerosis (VS) still represents the major obstacle for pulmonary graft survival in the medium and long term course after lung transplantation (LTX). Aside from nonspecific stimuli, early acute rejection (AR) seems to be causative especially in cases of a late diagnosis or inadequate treatment. This study investigated the effects of FTY720, a new immunosuppressant that promotes lymphocyte sequestration into lymph nodes and Peyer's patches, on the development of CR after experimental LTX. A total of 50 rats underwent allogenic (F344-to-WKY) and syngenic (WKY-to-WKY) left LTX. Group 1 animals had no treatment. Group 2 animals were administered FTY720 (3 mg/kg body weight per day) at the maximum time of AR (day 14) and continued up to day 100 after LTX. Group 3 animals were treated with the same dosage of FTY720 from day 0 to 100. The grades of AR and CR were classified according to the criteria of the International Society for Heart and Lung Transplantation. Within 14 days after allogenic LTX, all nontreated rats developed early AR followed by severe CR with VS and BO. Similar data were observed for FTY720 treatment of existing AR (group 2). Only early administration of FTY720 (at the time of LTX) significantly reduced the proportion of animals with severe acute vascular rejection (P < .001). However, all of these allografts showed high-grade acute airway inflammation. After long-term application, the chronic inflammatory response was absent; none of the allografts developed BO and VS. Only application of FTY720 immediately after LTX prevented lymphocyte recirculation and lung injury.


A new method for the precise and complete correction of distortion on cineangiographic image: its effect on left ventricular measurements.
Some of the problems associated with the precise evaluation of left ventricular volumes from angiographic images are due to the magnification and distortion of the pictures obtained from X-ray equipment. Magnification errors can be evaluated easily but the distortion (due to pincushion effect) are more difficult to measure. A mathematical method is proposed for a complete point-by-point correction of errors due to magnification and X-ray distortion. This method is applicable to most currently used angiographic equipment. Since more and more angiographic images are processed with local or remote digital computers, the applicability of the proposed technique becomes realistic. Results from this study show that a 5-30% overestimation of usual geometric ventricular parameters is encountered if no correction is made for distortion. End-diastolic measurements are more affected than end-systolic ones because of the greater degree of spherical distortion at the periphery of the picture area.


RNA-seq analysis and reconstruction of gene networks involved in response to salinity stress in quinoa (cv. Titicaca).
To better understand the mechanisms involved in salinity stress, the adaptability of quinoa cv. Titicaca-a halophytic plant-was investigated at the transcriptome level under saline and non-saline conditions. RNA-sequencing analysis of leaf tissue at the four-leaf stage by Illumina paired-end method was used to compare salt stress treatment (four days after stress at 13.8 dsm-1) and control. Among the obtained 30,846,354 transcripts sequenced, 30,303 differentially expressed genes from the control and stress treatment samples were identified, with 3363 genes expressed ≥ 2 and false discovery rate (FDR) of < 0.001. Six differential expression genes were then selected and qRT-PCR was used to confirm the RNA-seq results. Some of the genes (Include; CML39, CBSX5, TRX1, GRXC9, SnRKγ1 and BAG6) and signaling pathways discussed in this paper not been previously studied in quinoa. Genes with ≥ 2 were used to design the gene interaction network using Cytoscape software, and AgriGO software and STRING database were used for gene ontology. The results led to the identification of 14 key genes involved in salt stress. The most effective hub genes involved in salt tolerance were the heat shock protein gene family. The transcription factors that showed a significant increase in expression under stress conditions mainly belonged to the WRKY, bZIP and MYB families. Ontology analysis of salt stress-responsive genes and hub genes revealed that metabolic pathways, binding, cellular processes and cellular anatomical entity are among the most effective processes involved in salt stress.


A matched cohort study of radio-chemotherapy versus radiotherapy alone in soft tissue sarcoma patients.
Adjuvant radiotherapy is the standard postoperative treatment after conservative surgery in high risk soft tissue sarcoma. The role of adjuvant chemotherapy is still debated. Therefore, a matched cohort analysis was performed in high risk soft tissue patients to analyse differences in terms of clinical outcome and toxicity between patients treated with concomitant radio-chemotherapy (RTCT) and radiotherapy (RT) alone. For each patient in RT group was selected a patient in the RTCT group matching for age, T stage and grading. Acute and late toxicity were recorded, overall survival, recurrence free survival and distant metastases free survival were analysed and compared between the two groups. Ninety patients were selected, half of patients underwent radio-chemotherapy and half received radiotherapy alone. During the treatment Grade 3 dermatitis was recorded in 15 (16.7%) patients, 6 (6.7%) patients associated chemotherapy and during follow up 12 (13.3%) patients developed grade 2 late fibrosis, 3 (3.3%) joint stiffness and 1 (1.1%) patient experienced a bone fracture. There were no differences in the rate of acute and late toxicity between RTCT and RT alone group. Nineteen (21.1%) patients developed local recurrence, overall 5-year local relapse free survival was 83%. There were no differences between the two groups. 29 patients developed distant metastases, 14 (15.6%) patients in the RTCT group and 15 (16.7%) patients in the RT group. The 5-year distant metastases free survival was 67%. Age > 65 years was the only independent factor affecting distant recurrence (HR = 5.7, 95% CI 2.7-11.9; p = 0.001). At the time of analysis 15 (16.7%) patients were dead, 6 (6.7%) patients in the RTCT group and 9 (10%) patients in the RT group. 5-years overall survival was: 88%. At multivariate analysis age > 65 years was an independent prognostic factor of overall survival (HR = 3.7, 95% CI 1.2-12.1, p = 0.037). Prospective randomized studies with large size population and with subgroup analysis for histological subtypes are necessary to clarify the role of adjuvant chemotherapy in soft tissue sarcoma patients. Tailored treatment has to be considered in elderly soft tissue patients to guarantee a better outcome in this high risk and fragile population.


Knee joint repositioning error in different trunk positions among females with chronic nonspecific low back pain: A cross-sectional study.
Proprioception is a self-perceived sense of position and movement of one's body and its deficits can lead to motor control problems such as delayed muscle reflexes. Previous studies have confirmed lumbar proprioception impairments among individuals with Low Back Pain (LBP), which can afflict the normal central sensory-motor control and hence increases the risk of abnormal loading on the lumbar spine. Although the local investigation of proprioception is important, its influence on other joints in a kinetic chain particularly between extremities and spine should not be ignored. Therefore, the aim of this study was to compare the proprioception of knee joint in different trunk positions among females with chronic nonspecific low back pain (CNSLBP) and healthy females. The study included 24 healthy subjects and 25 patients with CNSLBP participated in this study. Repositioning error of knee joint in four different lumbar positions including flexion, neutral position, 50% ROM of left rotation and 50% ROM right rotation was evaluated using an inclinometer. Absolute error and constant error were obtained and analyzed. Absolute error in flexion and neutral positions in the individuals with CNSLBP were significantly higher than in healthy individuals; whereas, there was no significant difference in absolute and constant error between the two groups in 50% rotation to either side. This study showed that knee joint repositioning accuracy was reduced in patients with CNSLBP compared to healthy ones.


Different dietary starch patterns in low-protein diets: effect on nitrogen efficiency, nutrient metabolism, and intestinal flora in growing pigs.
Protein releases amino acids faster than starch releases glucose in digestive tract of pigs fed low-protein (LP) diets. Poor synchronization of dietary glucose and amino acids supply leads to compromised nitrogen efficiency. Dietary starch patterns modulation may improve this situation. Growing barrows (29.7 ± 2.0 kg) were randomly allotted into 5 dietary treatments with LP diets consisting of different purified starches. Treatments included: waxy corn starch (W LP), corn starch + waxy corn starch (C + W LP), corn starch (C LP), pea starch + waxy corn starch (P + W LP) and pea starch (P LP). In the experiment, growth performance, protein deposition, nutrient metabolism, and fecal microbial community of pigs were investigated. In vitro starch digestion was used for predicting the in vivo glucose response. Dietary starch in vitro glucose release profile was determined by starch source and the ratio of amylopectin and amylose. C + W LP treatment showed decreased total nitrogen excretion and plasma citrulline concentration and improved plasma leptin concentration among treatments (P < 0.05). Besides, the highest nitrogen apparent biological value, whole-body protein deposition and growth performance and lowest urinary nitrogen excretion were also observed in C + W LP treatment. Compared with the other groups, C + W LP and C LP showed increased plasma pyruvate, IGF-1, and lipase concentrations (P < 0.05). The W LP group presented dramatically increased plasma alanine and urea nitrogen concentration and decreased aldolase and leptin concentrations (P < 0.05). Dietary starch patterns did not make an impact on bacterial richness and diversity, but changed the taxonomic and functional structures of the microbial communities. Microbial protein fermentation product (isobutyrate and isovalerate) presented increased in P LP treatments compared with the other treatments (P < 0.05). Dietary starch patterns modulation can regulate dietary glucose release profile, nutrient metabolism, protein turnover, and fecal microbial fermentation in pigs. The optimal dietary glucose release profile effectively strengthened whole-body protein deposition and improve nitrogen efficiency and growth performance in growing pigs fed LP diets.


Nursing students' attitudes towards suicide and suicidal patients: A multicentre cross-sectional survey.
Education of nursing students can be a valuable resource in contributing to suicide prevention in mental health service users. The evaluation of students' attitudes towards a complex clinical issue is an important aspect of education that can expand traditional paths to acquisition of competence. Thus far, very few studies investigated attitudes towards suicidal risk among nursing students, and no data are available on Italian settings. The aim of this study was to explore nursing students' attitudes towards suicidal risk across the Nursing schools in three Italian universities. Multicentre cross-sectional survey incorporating a before-after design. A non-randomized sample of nursing students of the bachelor's degree in Nursing in three University hospitals was recruited. Nursing students completed "Suicide Behaviour Attitude questionnaire-Italian version" (SBAQ-ita scale); second-year nursing students of the University of Milan completed the scale before (T0) and 2 months after (T1) a specific lecture on suicide and suicidal risk. Three hundred and fourteen students were enrolled (response rate 76.77%). The overall score of sample attitudes had a Median (Me) of 3.5[2.5;4] for the domain "Feeling towards the patient", 3[2;4] for the domains "Professional ability", 5[3;7] for the domain "Right to suicide", 5[4;6] for the domain "Knowledge". Improved median score regarding the domain "Professional ability" (0.015), and decreased median score on the "Knowledge" (0.021) domain were observed at T1. The study highlights the impact of an educational intervention on nursing students' attitudes, supporting its implementation to improve academic education programmes.


Chlorophyll d and Acaryochloris marina: current status.
The discovery of the chlorophyll d-containing cyanobacterium Acaryochloris marina in 1996 precipitated a shift in our understanding of oxygenic photosynthesis. The presence of the red-shifted chlorophyll d in the reaction centre of the photosystems of Acaryochloris has opened up new avenues of research on photosystem energetics and challenged the unique status of chlorophyll a in oxygenic photosynthesis. In this review, we detail the chemistry and role of chlorophyll d in photosynthesis and summarise the unique adaptations that have allowed the proliferation of Acaryochloris in diverse ecological niches around the world.


HOXC9 overexpression is associated with gastric cancer progression and a prognostic marker for poor survival in gastric cancer patients.
As a member of the homeobox family, HOXC9 is overexpressed in several malignant tumors and may be regarded as a biomarker for prognostic evaluation. However, the expression pattern and prognostic significance of HOXC9 in gastric cancer have not been detailedly studied. HOXC9 mRNA expression difference in normal tissues and gastric cancer tissues were investigated using RT-PCR, and immunohistochemistry was used to analyze HOXC9 protein expression in precancerous lesions and gastric cancer at different stages, and its clinicopathological characteristics and survival were statistically tested. Compared to the normal gastric mucosa tissues, the expression levels of HOXC9 mRNA in the human gastric cancer tissues were significantly higher. HOXC9 protein levels of gastric cancer were obviously higher than that in other noncancerous tissues (P < 0.001). Positive expression of HOXC9 was associated with tumor size (P = 0.036), lymphatic invasion (P = 0.001), depth of invasion (P < 0.001), lymph-node metastasis (P < 0.001), and higher stage disease (P < 0.001). Furthermore, Kaplan-Meier survival curves showed that HOXC9 expression is inversely correlated with both disease-specific and disease-free 5 year survival of patients with gastric cancer (P < 0.001 for both). Strikingly, our multivariate Cox regression analysis revealed that HOXC9 expression was an independent poor prognostic factor in gastric cancer (P < 0.05). HOXC9 expression was observed in a subset of patients with gastric cancer and was associated with an unfavorable prognosis. As well as being a new prognostic indicator, HOXC9 protein could be a useful marker for early diagnosis.


Host-associated fitness variation in a seed beetle (Coleoptera: Bruchidae): evidence for local adaptation to a poor quality host.
The geographic distributions of many generalist herbivores differ from those of their host plants, such that they experience coarse-grained spatial variation in natural selection on characters influencing adaptation to host plants. Thus, populations differing in host use are expected to differ in their ability to survive and grow on these host plants. We examine host-associated variation in larval performance (survivorship, development time, and adult body weight) and oviposition preference, within and between two populations ofStator limbatus (Coleoptera: Bruchidae) that differ in the hosts available to them in nature. In one population,Acacia greggii (Fabaceae: Mimosoideae) andCercidium microphyllum (Fabaceae: Caesalpininoideae) are each abundant, while in the second population onlyC. floridum andC. microphyllum are present. In both populations, egg-to-adult survivorship was less than 50% onC. floridum, while survivorship was greater than 90% onA. greggii. Most of the mortality onC. floridum occurred as larvae were burrowing through the seed coat; very low mortality occurred during penetration of the seed coat ofA. greggii. Significant variation was present between populations, and among families (within populations), in survivorship and egg-to-adult development time onC. floridum; beetles restricted toCercidium in nature, without access toC. floridum, survived better and developed faster onC. floridum than beetles that had access toA. greggii. Large host effects on body size were detected for female offspring: females reared onA. greggii were larger than those reared onC. floridum, whereas male offspring wee approximately the same size regardless of rearing host. Trade-offs between performance onC. floridum andC. floridum were not detected in this experiment. Instead, our data indicate that development time and survivorship onC. floridum may be largely independent of development time and survivorship onA. greggii. Patterns of oviposition preference corresponded to the observed patterns of host suitability: in laboratory preference tests, beetles with access toA. greggii in nature tended to prefer this host more than beetles without access to this host in nature.


Spatial scale of tuberculosis transmission in Lima, Peru.
Spatially targeted interventions may be effective alternatives to individual or population-based prevention strategies against tuberculosis (TB). However, their efficacy may depend on the mechanisms that lead to geographically constrained hotspots. Local TB incidence may reflect high levels of local transmission; conversely, they may point to frequent travel of community members to high-risk areas. We used whole-genome sequencing to explore patterns of TB incidence and transmission in Lima, Peru. Between 2009 and 2012, we recruited incident pulmonary TB patients and their household contacts, whom we followed for the occurrence of TB disease. We used whole-genome sequences of 2,712 Mycobacterial tuberculosis isolates from 2,440 patients to estimate pariwise genomic distances and compared these to the spatial distance between patients' residences. Genomic distances increased rapidly as spatial distances increased and remained high beyond 2 km of separation. Next, we divided the study catchment area into 1 × 1 km grid-cell surface units and used household spatial coordinates to locate each TB patient to a specific cell. We estimated cell-specific transmission by calculating the proportion of patients in each cell with a pairwise genomic distance of 10 or fewer single-nucleotide polymorphisms. We found that cell-specific TB incidence and local transmission varied widely but that cell-specific TB incidence did not correlate closely with our estimates of local transmission (Cohen's k = 0.27). These findings indicate that an understanding of the spatial heterogeneity in the relative proportion of TB due to local transmission may help guide the implementation of spatially targeted interventions.


Alterations in human red blood cell membrane properties induced by the lipopolysaccharide from Proteus mirabilis S1959.
The effect of lipopolysaccharide (LPS, endotoxin), isolated from Proteus mirabilis S1959 strain, on red blood cell (RBC) membranes in whole cells as well as on isolated membranes was studied. Lipid membrane fluidity, conformational state of membrane proteins and the osmotic fragility of RBCs were examined using electron paramagnetic resonance spectroscopy and spectrophotometric method. Lipid membrane fluidity was determined using three spin-labeled fatty acids: 5-, 12- and 16-doxylstearic acid (5-, 12- and 16-DS). The addition of LPS S1959 to RBC suspension resulted in an increase in membrane fluidity, as indicated by 12-DS. At the concentrations of 0.5 and 1 mg/ml, LPS treatment led to a significant (P<0.05) increase in lipid membrane fluidity in the deeper region of lipid bilayer (determined by 12-DS). The conformational changes in membrane proteins were determined using two covalently bound spin labels, 4-maleimido-2,2,6,6-tetramethylpiperidine-1-oxyl and 4-iodoacetamido-2,2,6,6-tetramethylpiperidine-1-oxyl (ISL). The highest concentration of endotoxin significantly (P<0.05) decreased the relative rotational correlation time of ISL and significantly (P<0.05) increased the osmotic fragility of RBCs. The effect of endotoxin was much more profound in isolated membranes than in intact cells treated with LPS. At the concentrations 0.5 and 1 mg/ml, LPS led to a significant increase in h(w)/h(s) ratio. These results indicated increased membrane protein mobility, mainly in the spectrin-actin complex in membrane cytoskeleton. These data suggest that LPS-induced alterations in membrane lipids and cytoskeleton proteins of RBCs lead to loss of membrane integrity.


Pigmented villonodular synovitis: a retrospective study of seventy five cases (eighty one joints).
Pigmented villonodular synovitis (PVNS) is a relatively rare, benign proliferation lesion of the synovium of large joints, but there is not much information available about the disease's aetiology, clinical history, differential diagnosis, treatment, and long-term effects. We conducted a study to analyse these aspects of PVNS. We reviewed all clinical data for 75 patients with PVNS (81 joints) who were treated either by synovectomy alone or synovectomy plus arthroplasty. In all cases, the diagnosis of PVNS was confirmed by pathological examination. The ratio of males to females was 27:48, and the average age of patients was 46 years (range, 15-80 years). Lesions were located in the knee, hip, or ankle, and pain and swelling were the main symptoms. Of 75 patients, 42 had a history of trauma to the involved joint. Forty-one patients (43 joints) underwent synovectomy alone, and 34 patients (38 joints) underwent synovectomy and arthroplasty together. Of the 75 patients, 61 had full follow-up data. Twelve patients had recurrent legions detected by pathological examinations; four patients had more than two recurrences. Moreover, five patients developed PVNS after arthroplasty. PVNS occurs most often in middle-aged women and most frequently involves the knee, followed by the hip and ankle. The disease's etiology is varied and unclear. Surgical excision alone or with arthroplasty is an effective treatment, but there is a high rate of recurrence.