Levosimendan improves cardiac function, hemodynamics, and body inflammation in patients with acute myocardial infarction and heart failure.
To examine the effects of levosimendan on cardiac function, hemodynamics, and body inflammation of patients with acute myocardial infarction and heart failure. A retrospective analysis was conducted on 113 acute myocardial infarction patients with heart failure (admitted to Xianyang First People's Hospital from September 2018 to January 2022). According to the treatment plan, patients were categorized into a control group (n = 53) (treated with conventional diuresis and vasodilation) and observation group (n = 60) (treated with levosimendan in addition to the treatment of the control group). Indexes were compared between the two groups before and after treatment, including effectiveness rate, mean pulmonary arterial pressure (PAMP) and pulmonary capillary wedge pressure (PCWP). Left ventricular end-diastolic diameter (LVEDD), left ventricular end-systolic diameter (LVESD) and left ventricular ejection fraction (LVEF) were monitored before and after treatment by color Doppler ultrasonography. Serum high-sensitivity C-reactive protein (hs-CRP) levels were measured before and after treatment. Logistic analysis was applied to screen independent factors affecting treatment efficacy. Adverse reactions and life quality after 6 months of treatment were compared between the two groups. The overall response rate of the observation group was higher than that of the control group (P<0.05). Changes in PAMP and PCWP in the two groups before and after treatment were significantly different. Patients in the observation group had improved indicators compared with the control group (all P<0.05). After treatment, the cardiac function indexes and inflammation-related factors of the observation group were improved more than those of the control group (P<0.05). Patients in the observation group had a lower incidence of adverse reactions and a higher life quality 6 months after treatment compared to the control group (P<0.05). Diabetes and treatment regimen were independent risk factors affecting treatment efficacy by logistic regression analysis. The administration of levosimendan helps improve cardiac function, hemodynamics, and body inflammation in patients with acute myocardial infarction and heart failure, with fewer adverse reactions and higher safety.


The Pseudomonas aeruginosa ExoY phenotype of high-copy-number recombinants is not detectable in natural isolates.
The nucleotidyl cyclase ExoY is an effector protein of the type III secretion system of Pseudomonas aeruginosa We compared the cyclic nucleotide production and lung disease phenotypes caused by the ExoY-overexpressing strain PA103ΔexoUexoT::Tc pUCPexoY, its vector control strain PA103ΔexoUexoT::Tc pUCP18, its loss-of-function control PA103ΔexoUexoT::Tc pUCPexoY K81M and natural ExoY-positive and ExoY-negative isolates in a murine acute airway infection model. Only the P. aeruginosa carrier of the exoY-plasmid produced high levels of cUMP and caused the most severe course of infection. The pathology ascribed to ExoY from studies using the high-copy-number plasmid on mammalian cells in vitro and in vivo was not observed with natural P. aeruginosa isolates. This indicates that the role of ExoY during infection with real-life P. aeruginosa still needs to be resolved.


Plasma somatomedin-binding proteins in hypopituitarism: changes during growth hormone therapy.
The somatomedin (SM) peptides are carried in plasma complexed to specific SM-binding proteins (SMBPs). In addition to the SMBP in the complex, there is an unsaturated SMBP in plasma in which the SMBP is not occupied by SMs. We have compared levels of unsaturated SMBP in 7 normal adults to those in 21 children with GH deficiency before and during treatment with hGH (0.1 U/kg.day) for 4 days. In addition, the SM-C/insulin-like growth factor I (IGF-I) content of each plasma was measured by RIA. There was a significant (P less than 0.01) difference in unsaturated SMBP levels between normal controls (17.8 +/- 0.8% bound/20 microliters) and untreated hypopituitary patients (27.8 +/- 2.2% bound/20 microliters). Thus, a lower SM-C/IGF-I content was associated with a higher unsaturated SMBP level. Furthermore, there was a significant negative correlation between SM-C/IGF-I content and unsaturated SMBP in untreated hypopituitary patients (r = 0.73; P less than 0.0001). Treatment with hGH normalized the mean unsaturated SMBP level in hypopituitary patients within 2 days. Full displacement curves and Scatchard analysis showed that the increased unsaturated SMBP level in hypopituitary plasma was entirely due to an increased affinity (8.4 X 0.9 X 10(-10) M) compared to normal (2.3 X 0.2 X 10(-9) M). A higher affinity form of unsaturated SMBP is uniquely present in hypopituitarism and disappears with hGH treatment. The measurement of this unsaturated SMBP mirrors the SM peptide content.


Scanning electron microscope studies of turkey semen.
Turkey spermatozoa were examined morphologically with the aid of a Cambridge Stereoscan electron microscope. Mean dimensions, in micra, of normal spermatozoa were: acrosome, 1.8; nucleus, 9.1; midpiece, 4.8; tail, 61.0; total length 76.7. The maximum diameter of the head at its widest was 0.8 microns. There was an increase in abnormal spermatozoa in yellowish semen, with coiling being the most prevalent abnormality. The spherical-shaped cells with granular appearance, also present in yellowish semen, were ascertained to be large macrophages. Occasionally, macrophages filled with phagocytized sperm cells were evident. Hens inseminated with yellowish semen had 57.6 percent fertility compared to 92.1 percent for hens inseminated with control semen.


Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress.
Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) is the primary transcription factor protecting cells from oxidative stress by regulating cytoprotective genes, including the antioxidant glutathione (GSH) pathway. GSH maintains cellular redox status and affects redox signaling, cell proliferation, and death. GSH homeostasis is regulated by de novo synthesis as well as GSH redox state; previous studies have demonstrated that Nrf2 regulates GSH homeostasis by affecting de novo synthesis. We report that Nrf2 modulates the GSH redox state by regulating glutathione reductase (GSR). In response to oxidants, lungs and embryonic fibroblasts (MEFs) from Nrf2-deficient (Nrf2(-/-)) mice showed lower levels of GSR mRNA, protein, and enzyme activity relative to wild type (Nrf2(+/+)). Nrf2(-/-) MEFs exhibited greater accumulation of glutathione disulfide and cytotoxicity compared to Nrf2(+/+) MEFs in response to t-butylhydroquinone, which was rescued by restoring GSR. Microinjection of glutathione disulfide induced greater apoptosis in Nrf2(-/-) MEFs compared to Nrf2(+/+) MEFs. In silico promoter analysis of the GSR gene revealed three putative antioxidant-response elements (ARE1, -44; ARE2, -813; ARE3, -1041). Reporter analysis, site-directed mutagenesis, and chromatin immunoprecipitation assays demonstrated binding of Nrf2 to two AREs distal to the transcription start site. Overall, Nrf2 is critical for maintaining the GSH redox state via transcriptional regulation of GSR and protecting cells against oxidative stress.


Modeling subject-specific phase-dependent effects and variations in longitudinal responses via a geometric Brownian motion process.
We address statistical issues regarding modeling a collection of longitudinal response trajectories characterized by the presence of subject-specific phase-dependent effects and variation. To accommodate these two time-varying individual characteristics, we employ a geometric stochastic differential equation for modeling based on a Brownian motion process and develop a two-step paradigm for statistical analysis. This paradigm reverses the order of statistical inference in random effects model. We first extract individual information about phase-dependent treatment effects and volatility parameters for all subjects. Then, we derive the association relationship between the parameters characterizing the individual longitudinal trajectories and the corresponding covariates by means of multiple regression analysis. The stochastic differential equation model and the two-step paradigm together provide significant advantages both in modeling flexibility and in computational efficiency. The modeling flexibility is due to the easy adaptation of temporal change points for subject-specific phase transition in treatment effects, whereas the computational efficiency benefits in part from the independent increment property of Brownian motion that avoids high-dimensional integration. We demonstrate our modeling approach and statistical analysis on a real data set of longitudinal measurements of disease activity scores from a rheumatoid arthritis study.


Supraventricular tachycardia. Doing the right things.
Supraventricular tachycardia is an outmoded term which, while widely used, is imprecise and is impeding the development of antiarrhythmic management strategies. Precise arrhythmia descriptions, recognition of the arrhythmogenic basis of the arrhythmia and an appreciation of the variety of therapeutic approaches available is an essential part of modern day medicine. The selected strategy will be dictated by an accurate assessment of how the arrhythmia disadvantages the patient. Good clinical practice will ensure constant monitoring of the effect of and need for therapy. The 'right things' in arrhythmia management can now be defined and should form the basis of new, practical, clinical protocols.


Trunk radial growth, water and carbon relations of mature apple trees on two size-controlling rootstocks during severe summer drought.
The use of size-controlling rootstocks is central to modern high-density fruit production systems. While biological mechanisms responsible for vigor control are not fully understood, differences in water relations and carbohydrate storage ability have been suggested as two potential factors. To better understand the processes that control growth vigor, we analyzed the trunk radial variation at seasonal and diurnal timescales and measured the midday leaf water potential (ΨMD), leaf gas exchange and concentrations of non-structural carbohydrates (NSC) in apple trees of variety 'Jonagold' grafted on two rootstocks of contrasting growth vigor (dwarfing J-TE-G vs invigorating J-TE-H). The measurements were conducted during an exceptionally hot and dry summer. We found that smaller annual trunk radial increments in dwarfed trees were primarily due to an earlier cessation of trunk secondary growth. The interdiurnal trunk circumference changes (ΔC) were slightly lower in dwarfed trees, and these trees also had fewer days with positive ΔC values, particularly during the driest summer months. The trunks of dwarfed trees shrank gradually during the drought, showed less pronounced diurnal variation of trunk circumference and the maximum trunk daily shrinkage was only weakly responsive to the vapor pressure deficit. These results indicated that lower turgidity in the cambial region may have limited the trunk radial expansion in dwarfed trees during the hot and dry days. Dwarfed trees also maintained lower ΨMD and leaf gas exchange rates during the summer drought. These parameters decreased in parallel for both rootstock combinations, suggesting their similar drought sensitivity. Similar concentrations and seasonal dynamics of NSC in both rootstock combinations, together with their similar spring growth rates, suggest that NSC reserves were not directly limiting for growth. Our results support the prominent role of water relations in rootstock-induced size-controlling mechanisms and highlight the complexity of this topic.


Effects of dry matter and energy intake on quality of oocytes and embryos in ruminants.
The success of herd fertility involves the development of healthy follicles, viable oocytes and embryos capable of establishing and maintaining a pregnancy. Herein we discuss how nutrition interacts with reproduction throughout follicle development and pregnancy establishment, focusing on dry matter and energy intake. High feed intake, especially associated with moderate to high body condition, before and through superstimulation protocols, natural or induced single-ovulations or before ovum pick-up has detrimental effects on the quality of oocytes or embryos. Feed restriction or high energy supply can be used strategically to obtain either more or better quality oocytes or embryos. Altering diets that provide different concentrations of circulating insulin may improve ovarian status, oocyte quality, embryo development and pregnancy establishment and maintenance. Some sources of fat can positively affect reproductive performance, such as polyunsaturated fatty acids, improving embryo quality and pregnancy. In contrast, fat supplementation in the diet may compromise embryo cryotolerance. Finally, nutrition can alter concentrations of circulating or intrafollicular hormones and metabolites and the expression of genes in cattle oocytes and embryos. For an adequate feeding program to benefit reproductive performance, factors such as genetic group, source of energy, metabolic status, physiological status and level of feed intake must be taken into account.


Orientational and translational dynamics of polyether/water solutions.
Optical heterodyne-detected optical Kerr effect (OHD-OKE) experiments and pulsed field-gradient spin-echo NMR (PFGSE-NMR) experiments were performed to measure the rotational and translational diffusion constants of a polyether, tetraethylene glycol dimethyl ether (TEGDE), in binary mixtures with water over concentrations ranging from pure TEGDE to approaching infinite dilution. In addition, hydrodynamic calculations of the rotational and translational diffusion constants for several rigid TEGDE conformations in the neat liquid and in the infinitely dilute solution were performed to supplement the experimental data. The rotational relaxation data follow the Debye-Stokes-Einstein (DSE) equation within experimental error over the entire water concentration range. The agreement with the DSE equation indicates that there is no significant structural change of the polyether as the water content is changed. In contrast to the rotational dynamics, the translational diffusion data show a distinct deviation from Stokes-Einstein (SE) behavior. As the water content of the mixture is reduced, the translational diffusion rate decreases less rapidly than the increase in viscosity alone predicts until the water/TEGDE mole ratio of 7:1 is reached. Upon further reduction of water content, the translational diffusion tracks the viscosity. Comparison of the translational data with the rotational data and the hydrodynamic computations shows that the translational dynamics cannot be explained by a molecular shape change and that the low water fraction solutions are the ones that deviate from hydrodynamic behavior. A conjecture is presented as a possible explanation for the different behaviors of the rotational and translational dynamics.


Prevalence and Clinical Significance of Respiratory Effort-Related Arousals in the General Population.
To determine the prevalence and clinical associations of respiratory effort-related arousals (RERA) in a general population sample. A total of 2,162 participants (51.2% women, 58.5 ± 11.0 years old, body mass index [BMI] 25.6 ± 4.2 kg/m2) of a general population-based cohort (HypnoLaus, Switzerland) underwent full polysomnography at home. Each subject with a RERA index ≥ 5 events/h was compared with an age-, sex- and apnea-hypopnea index (AHI)-matched control without RERA. A RERA index ≥ 5 events/h was present in 84 participants (3.8%; 95% confidence interval: 3.2-4.8%). In 17 participants (0.8%; 95% confidence interval: 0.5-1.3%), RERAs were the predominant sleep breathing disorder and only one of them complained of excessive daytime sleepiness. Compared to matched controls, subjects with a RERA index ≥ 5 events/h were similar in terms of BMI (26.5 ± 3.5 versus 26.3 ± 4.8 kg/m2, P = .73), neck circumference (38.5 ± 3.3 versus 37.6 ± 3.7 cm, P = .10) and Epworth Sleepiness Scale score (6.7 ± 3.7 versus 6.0 ± 3.7, P = .22). Also, no differences were found for hypertension (21.4% versus 27.4%, P = .47), diabetes (7.1% versus 7.1%, P = 1.00), or metabolic syndrome (31.0% versus 23.8%, P = .39). In a middle-aged population-based cohort, the prevalence of a RERA index ≥ 5 events/h was low (3.8%) and was not associated with negative clinical outcomes when using the currently recommended scoring criteria of the American Academy of Sleep Medicine.


Cytotoxic Potential of the Marine Diatom Thalassiosira rotula: Insights into Bioactivity of 24-Methylene Cholesterol.
Marine microalgae are receiving great interest as sustainable sources of bioactive metabolites for health, nutrition and personal care. In the present study, a bioassay-guided screening allowed identifying an enriched fraction from SPE separation of the methanolic extract of the marine diatom Thalassiosira rotula with a chemically heterogeneous composition of cytotoxic molecules, including PUFAs, the terpene phytol, the carotenoid fucoxanthin and the phytosterol 24-methylene cholesterol (24-MChol). In particular, this latter was the object of deep investigation aimed to gain insight into the mechanisms of action activated in two tumour cell models recognised as resistant to chemical treatments, the breast MCF7 and the lung A549 cell lines. The results of our studies revealed that 24-MChol, in line with the most studied β-sitosterol (β-SIT), showed cytotoxic activity in a 3-30 µM range of concentration involving the induction of apoptosis and cell cycle arrest, although differences emerged between the two sterols and the two cancer systems when specific targets were investigated (caspase-3, caspase-9, FAS and TRAIL).


Influence of Nest Box Color and Release Sites on Osmia lignaria (Hymenoptera: Megachilidae) Reproductive Success in a Commercial Almond Orchard.
Intensively managed, commercial orchards offer resources for managed solitary bees within agricultural landscapes and provide a means to study bee dispersal patterns, spatial movement, nest establishment, and reproduction. In 2012, we studied the impact of 1) the color of nest boxes covaried with four nest box density treatments and 2) the number of bee release sites covaried with two nest box density treatments on the reproductive success of Osmia lignaria Say in a California almond orchard pollinated by a mixture of O. lignaria and Apis mellifera L. Nest box color influenced the number of nests, total cells, and cells with male and female brood. More nests and cells were produced in light blue nest boxes than in orange or yellow nest boxes. The covariate nest box density also had a significant effect on brood production. The number of release sites did not affect O. lignaria nesting and reproduction, but the number of cavities in nest boxes influenced reproduction. Overall, the color of nest boxes and their distribution, but not the number of release sites, can greatly affect O. lignaria nest establishment and reproductive success in a commercial almond orchard. The ability to locate nesting sites in a homogenous, large orchard landscape may also be facilitated by the higher frequency of nest boxes with low numbers of cavities, and by the ability to detect certain nest box colors that best contrast with the blooming trees.


Construction of a literature database and its use to provide probabilities for decision-analytic models of thrombolytic therapy.
Probabilities for decision-analytic models are routinely obtained from the medical literature. This study describes development and use of a literature database to facilitate obtaining probabilities for decision-analytic models of thrombolytic therapy for acute myocardial infarction. Implementation demonstrates the concept of a literature database to be both feasible and effective. Specific difficulties encountered in the evaluation of continuous variables, the potential storage of actual probabilities, and the advantage for easy growth with the literature are discussed.


Streamlined Synthesis and Assembly of a Hybrid Sensing Architecture with Solid Binding Proteins and Click Chemistry.
Combining bioorthogonal chemistry with the use of proteins engineered with adhesive and morphogenetic solid-binding peptides is a promising route for synthesizing hybrid materials with the economy and efficiency of living systems. Using optical sensing of chloramphenicol as a proof of concept, we show here that a GFP variant engineered with zinc sulfide and silica-binding peptides on opposite sides of its β-barrel supports the fabrication of protein-capped ZnS:Mn nanocrystals that exhibit the combined emission signatures of organic and inorganic fluorophores. Conjugation of a chloramphenicol-specific DNA aptamer to the protein shell through strain-promoted azide-alkyne cycloaddition and spontaneous concentration of the resulting nanostructures onto SiO2 particles mediated by the silica-binding sequence enables visual detection of environmentally and clinically relevant concentrations of chloramphenicol through analyte-mediated inner filtering of sub-330 nm excitation light.


Operando Spectroscopy Observation of Mo Clusters-Ti3 C2 TX Catalyst/Support Interface's Dynamic Evolution in Hydrogen Evolution Reaction.
The interaction between catalyst and support plays an important role in electrocatalytic hydrogen evolution (HER), which may explain the improvement in performance by phase transition or structural remodeling. However, the intrinsic behavior of these catalysts (dynamic evolution of the interface under bias, structural/morphological transformation, stability) has not been clearly monitored, while the operando technology does well in capturing the dynamic changes in the reaction process in real time to determine the actual active site. In this paper, nitrogen-doped molybdenum atom-clusters on Ti3 C2 TX (MoACs /N-Ti3 C2 TX ) is used as a model catalyst to reveal the dynamic evolution of MoAcs on Ti3 C2 TX during the HER process. Operando X-ray absorption structure (XAS) theoretical calculation and in situ Raman spectroscopy showed that the Mo cluster structure evolves to a 6-coordinated monatomic Mo structure under working conditions, exposing more active sites and thus improving the catalytic performance. It shows excellent HER performance comparable to that of commercial Pt/C, including an overpotential of 60 mV at 10 mA cm-2 , a small Tafel slope (56 mV dec-1 ), and high activity and durability. This study provides a unique perspective for investigating the evolution of species, interfacial migration mechanisms, and sources of activity-enhancing compounds in the process of electroreduction.


Acute post-irradiation canine intestinal blood flow.
Radiation-induced early transient incapacitation (ETI) is accompanied by severe systemic hypotension, during which arterial blood pressure often decreases to less than 50 per cent of normal. One haemodynamic compensatory mechanism is increased peripheral resistance due to vasoconstriction. This vasoconstriction in the small intestine of dogs is disproportionately increased during haemorrhagic or endotoxic shock, and intestinal ischaemia is frequent. In an attempt to elucidate mechanisms underlying radiation-induced ETI and the gastrointestinal radiation syndrome, canine intestinal submucosal blood flow was measured by the hydrogen polarographic technique, both before and after exposure to gamma radiation. Systemic blood pressures, blood gases and haematocrits were determined simultaneously. Data obtained from 12 sham-irradiated dogs and 12 irradiated dogs indicated that 90 Gy, whole-body, gamma radiation produced a 31 per cent decrease in systemic mean blood pressure beginning within 20 min post-irradiation and lasting for at least 90 min. However, the intestinal submucosal blood flow did not decrease as anticipated, but it exhibited an actual post-irradiation increase. This increase in post-irradiation intestinal submucosal blood flow began within 5 min after irradiation and lasted for at least 90 min. Post-irradiation haematocrits were 10.5 per cent higher than those obtained before irradiation and those obtained from sham-irradiated subjects. Histopathological examination of ileal mucosa revealed significant pathologic lesions in some irradiated animals within two hours after exposure.


Epithelioid sarcoma of soft tissues: a case of extrarenal renin-secreting tumour.
The case of a young woman presenting with a renin-secreting soft tissue sarcoma is described. The primary extrarenal tumour as well as metastatic disease were associated with severe hypertension and both required surgical treatment. The location of these rare malignant tumours and their association with renin-dependent hypertension is discussed. In cases of this type, reappearance of hypertension suggests tumour recurrence.


The influence of heat shock protein 70 induction on hemodynamic variables in a porcine model of recurrent endotoxemia.
The manipulation of stress gene expression by heavy metals provides protection against the lethal effects of endotoxemia in murine models of septic shock. These findings suggest that the increased resistance to endotoxin in vivo after stress protein induction could be explained by an attenuation of hemodynamic alterations and an altered pattern of inflammatory mediator release. Therefore, we measured main hemodynamic variables such as systemic and pulmonary artery pressure, cardiac output, heart rate, central venous pressure, and pulmonary artery wedge pressure, as well as the time-course of thromboxane-B2, 6-keto-PGF1 alpha, and interleukin 6 formation with and without induction of the stress response in an established porcine model of recurrent endotoxemia (Circ Shock 35:237-244, 1991). Induction of the stress response was carried out by a pretreatment with Zn2+ (25 mg/kg zinc-bis-(DL-hydrogenaspartate) = 5 mg/kg Zn2+). Pretreatment with Zn2+ prior to lipopolysaccharide (LPS) infusion induced an increased heat shock protein 70 (HSP70) expression in the lungs, liver, and kidneys and significantly increased plasma levels of interleukin 6, 6-keto-PGF1 alpha, and thromboxane-B2, compared with untreated controls. After LPS infusion, however, pretreated animals showed significantly decreased peak plasma levels of all mediators compared with the untreated group. Hemodynamic data presented significantly decreased peak pulmonary artery pressure and pulmonary vascular resistance index values, significantly increased systemic artery pressure and systemic vascular resistance index values, and significantly altered hypodynamic/hyperdynamic cardiac output levels in the pretreated group. In conclusion, the data show that the induction of HSP70 by Zn2+ attenuates the liberation of inflammatory mediators, as well as the course of hemodynamic variables due to LPS.


Early tumor shrinkage as a predictive factor of metastatic renal cell carcinoma in molecular targeted therapy: A single institutional study.
The aim of the present study was to investigate the impact of metastatic sites and early tumor shrinkage (eTS) as prognostic predictive factors of metastatic renal cell carcinoma (mRCC) in molecular targeted therapy. A total of 209 advanced RCC cases treated with sorafenib, sunitinib, axitinib, pazopanib, temsirolimus and everolimus from our single institution were included in the present study. Several known prognostic predictive factors, including metastatic sites and the rate of eTS, were analyzed by Kaplan-Meier survival estimate analysis followed by Cox's proportional hazards model analysis. eTS was measured by three independent physicians. Four metastatic sites in the liver, bone, lymph nodes and brain as well as greater eTS were identified as potential independent predictors of overall survival (OS) in several cohorts: i) Metastatic RCC (n=194); ii) metastatic clear cell RCC (n=119); and iii) mRCC patients with eTS data (n=127). In sub-analyses of patients treated with each 1st line tyrosine kinase inhibitor, eTS was identified as a potentially potent predictor of OS in patients treated with axitinib. The liver, bone, lymph nodes, brain metastases and eTS were identified as independent predictive factors of OS by analyzing a limited Japanese cohort.


Simultaneous plasma determination of CEA, HCG-beta and beta-2-microglobulin in patients with nontrophoblastic tumors.
With the object of studying the possible usefulness of the simultaneous plasma determination of CEA, HCG-beta and beta 2-microglobulin in patients with nontrophoblastic tumors, we measured by radioimmunoassay the concentrations of these substances in 77 patients with normal renal function. In the group without metastases (32 cases), the percentages of positives we low and similar for the 3 tumor markers. In the group with metastases (45 cases), the X2 test of independence between each of the 2 markers at a level of 95 % showed a relationship between the results obtained in the determination of HCG-beta and beta 2-microglobulin, as an independence between CEA and HCG-beta results and CEA and beta 2-microglobulin results. These data suggest the utility of determining CEA with only 1 of the other 2 antigens in disseminated tumors.


Clinical Outcomes of Radiotherapy in Elderly and Younger Patients With T4 Esophageal Cancer: A Retrospective Single-center Analysis.
The standard of treatment for esophageal cancer with adjacent organ invasion (T4) has not been established. We retrospectively analyzed the clinical outcomes of radiotherapy (RT) in elderly and younger patients with T4 esophageal cancer. Sixty-nine patients with T4 esophageal cancer who underwent RT at the Kanagawa Cancer Center between January 2014 and November 2020 were included in this study. Patients aged ≥70 years were defined as the elderly group and those aged <70 years were defined as the younger group. The total dose of RT was set at 60 Gy in 30 fractions. Chemotherapy combined with 5-fluorouracil and cisplatin was administered concurrently with RT in general. The overall survival (OS) rate was estimated using the Kaplan-Meier method. Adverse events were assessed using CTCAE v4.0. The median survival time (MST) of the elderly group (n=35) was 21.5 months, and the OS rates at 1, 3, and 5 years were 63.7%, 31.3%, and 15.6%, respectively. The MST of the younger group (n=34) was 12.5 months, and the OS rates at 1, 3, and 5 years were 52.2%, 29.4%, and 29.4%, respectively. No significant difference in OS was observed between the two groups (p=0.767). Toxicities were not significantly different between the two groups except for thrombocytopenia and esophageal fistula (p=0.012 and p=0.022, respectively). The clinical outcomes of RT for T4 esophageal cancer in elderly patients were generally similar to those in the younger group.


Small hepatocellular carcinoma with ring calcification: a case report and literature review.
Ring calcification in untreated hepatocellular carcinoma (HCC) is extremely rare, with only 3 previously reported cases in the English-language literature. A case of HCC with ring calcification was reported in this paper. Additionally, 3 previously reported cases of HCC with ring calcification were reviewed. In 3 of these 4 cases (including our case), surgery was performed. Although the size of the ring-calcified lesion ranged from 3.0-3.7 cm in previously reported cases, the size was only 1 cm in ours. The differentiation of the tumor was moderate in the 2 previously reported cases in the histological findings and poor in ours. In spite of their poor differentiation for their sizes, these tumors showed no early enhancement in dynamic computed tomography. All calcified tumors showed a thick fibrous capsule and extensive necrosis histologically. Ring calcification was considered to result from a circulatory disturbance caused by the imbalance between the less abundant arterial blood flow and high inner pressure induced by either the thick fibrous capsule or vigorous proliferation due to the poor differentiation. Ring calcification in untreated HCC may suggest a lower differentiation of the tumor. Even if its size is small, hepatic resection should be performed for any tumor with ring calcification because poor differentiation is considered to be one of the risk factors for recurrence after local ablation therapy, including radio frequency ablation.


Pili canaliculi as manifestation of giant axonal neuropathy.
Giant axonal neuropathy is a rare autosomal recessive neurodegenerative disease. The condition is characterized by neurons with abnormally large axons due to intracellular filament accumulation. The swollen axons affect both the peripheral and central nervous system. A 6-year old female patient had been referred to a geneticist reporting problems with walking and hypotonia. At the age of 10, she became wheelchair dependent. Scanning electron microscopy of a curly hair classified it as pili canaliculi. GAN gene sequencing demonstrated mutation c.1456G>A (p.GLU486LYS). At the age of 12, the patient died due to respiratory complications. Dermatologists should be aware of this entity since hair changes are considered suggestive of GAN.


Vertical drying of a suspension of sticks: Monte Carlo simulation for continuous two-dimensional problem.
The vertical drying of a two-dimensional colloidal film containing zero-thickness sticks (lines) was studied by means of kinetic Monte Carlo (MC) simulations. The continuous two-dimensional problem for both the positions and orientations was considered. The initial state before drying was produced using a model of random sequential adsorption with isotropic orientations of the sticks. During the evaporation, an upper interface falls with a linear velocity in the vertical direction, and the sticks undergo translational and rotational Brownian motions. The MC simulations were run at different initial number concentrations (the numbers of sticks per unit area), p_{i}, and solvent evaporation rates, u. For completely dried films, the spatial distributions of the sticks, the order parameters, and the electrical conductivities of the films in both the horizontal, x, and vertical, y, directions were examined. Significant evaporation-driven self-assembly and stratification of the sticks in the vertical direction was observed. The extent of stratification increased with increasing values of u. The anisotropy of the electrical conductivity of the film can be finely regulated by changes in the values of p_{i} and u.


Efficacy of Zofenopril vs. Irbesartan in Combination with a Thiazide Diuretic in Hypertensive Patients with Multiple Risk Factors not Controlled by a Previous Monotherapy: A Review of the Double-Blind, Randomized "Z" Studies.
Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18-24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (-0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the recommendations of current guidelines.


Serological relationships among budding, prosthecate bacteria.
The somatic antigens of 25 strains of budding bacteria were typed and 14 serologically distinct groups were identified, suggesting considerable antigenic diversity among hyphomicrobia. Ten of the groups were represented by a single isolate, 2 contained two isolates, 1 three isolates, and 1 eight isolates. The strains in the largest group of eight isolates each shared at least one common antigen. However, there was also considerable antigenic heterogeneity within this cluster. Serological activity resided in the lipopolysaccharide (LPS) portion of cell walls and also in a heat labile component of Hyphomicrobium neptunium. The amino acid utilizing isolates, H. neptunium and Hyphomonas polymorpha, were serologically unrelated and it is suggested that the two organisms could be grouped as members of the same genus but not the same species.


[A case report of idiopathic thrombocytosis in 27-year-old man treated for myocardial infarction].
We present the case of 27-year-old male, physical training teacher in whom the first clinical sign of idiopathic thrombocytosis was myocardial infarction. The infarct was complicated by heart arrest caused by ventricular fibrillation. Streptolysis (streptokinase) was used in treatment. Thrombocytosis 842 G/l was observed in blood tests at admission. To estimate its cause the bone marrow biopsy and trepanobiopsy of hip bone were performed. Tests were performed to exclude the secondary cause of thrombocytosis. The coronarography did not show relevant stenoses of coronary arteries. The results let diagnose myocardial infarction in a patient with essential thrombocytosis.


What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study.
Over 38,000 new cases of lung cancer occur each year in the UK. Most are diagnosed after initial presentation to primary care, but the relative importance of the various clinical features is largely unknown. A population based case-control study was undertaken in all 21 general practices in Exeter, Devon, UK (population 128 700). 247 primary lung cancers were studied in subjects aged over 40 years diagnosed between 1998 and 2002 and 1235 controls matched by age, sex and general practice. The entire primary care record for 2 years before diagnosis was coded using the International Classification of Primary Care-2. Univariable and multivariable conditional logistic regression analyses were used to identify and quantify clinical features independently associated with lung cancer. The main outcome measures were odds ratios and positive predictive values for these variables. Seven symptoms (haemoptysis, loss of weight, loss of appetite, dyspnoea, thoracic pain, fatigue and cough), one physical sign (finger clubbing), and two abnormal investigation results (thrombocytosis and abnormal spirometry) were associated with lung cancer in multivariable analyses, as was cigarette smoking. After excluding variables reported in the final 180 days before diagnosis, haemoptysis, dyspnoea and abnormal spirometry remained independently associated with cancer. This study provides an evidence base for selection of patients for investigation of possible lung cancer, both for clinicians and for developers of guidelines.


Studies on the oxygen supply of heterotopic auxiliary liver grafts in rats.
Heterotopic auxiliary liver transplantations were performed in rats using the method of Hess et. al. [6]. Oxygen pressure of liver tissue was measured with a Pt-surface electrode of Kessler and Lübbers [10]. After ligation of the hepatic artery, liver tissue PO2 decreased and remained low during further preparation. Only two of the seven lobes of the rat liver (= 30% of the parenchyma) were used as a graft. After revascularization and application of a gelatine plasma substitute, tissue PO2 of the graft increased to values of normal rat liver, although the graft was supplied with portal blood only. We suggest that one reason for this is the increase of portal perfusion rate, for the whole amount of portal blood perfuses only 30% of liver parenchyma. In the first month after transplantation PO2 of the graft parenchyma was low, but increased continually in the following months, reaching PO2 values of normal rat livers after 1 year.


Incidental finding of a primary thyroid tuberculosis.
Thyroid tuberculosis (TT) is a very rare condition, even in countries where tuberculosis is endemic. However, the prevalence of tuberculosis has increased worldwide and thyroid involvement can be a primary manifestation of the disease. We present the case of a 43-year-old patient with this diagnosis and perform a review of the related literature. After searching for similar case reports in Western Europe since 2010 we identified six cases in four countries. TT should be considered in the differential diagnosis of a thyroid nodule. Fine-needle aspiration cytology and polymerase chain reaction are useful tools as preoperative diagnosis. Typical caseous necrotic granulomas are the hallmark in biopsy.


A qualitative examination of the impact of microgrants to promote physical activity among adolescents.
Microgrants are a mechanism for providing funding to community organizations or groups to support health initiatives. Little research to date has examined the use of microgrants in promoting physical activity (PA), and no studies have explored how microgrants may support PA promotion among adolescents. The purpose of this study was to explore the role of microgrants in enhancing PA opportunities for Canadian adolescents. Employing a case study approach, nine community organizations from across Canada were selected as cases providing sports and physical activities with the support of microgrant funding. Researchers visited each organization and conducted semi-structured interviews with 40 program participants (12-25 years of age, M = 16.3, SD = 2.6) and 17 adult organizers/instructors (23-57 years of age, M = 37.4, SD = 10.0). Interview transcripts were inductively and deductively coded to identify concepts and create a hierarchy of themes. Analysis produced themes regarding participants' perceptions of the Funding, Running Programs and Events, the Impact of Program (for the Organization, Teen Participants, and the Community). Opportunities for PA programming would not have been possible without the microgrant funding. Microgrant funding was valuable in promoting PA for adolescents, and they afforded opportunities for adolescents to engage in new and/or nontraditional activities. In addition to promoting PA, the microgrants had benefits for participants and the community organizations including improved organizational capacity. Microgrants appear to be an effective mechanism for enhancing community capacity to provide PA opportunities for Canadian adolescents by helping to reduce financial barriers and empowering adolescents to take an active role in identifying and hosting new and creative PA events within their communities.


Requirement of MHC class I antigen expression on human tumors for in vitro recognition by autologous blood lymphocytes.
Expression of class I antigens on ex-vivo tumor cells was found to be required for their recognition by autologous blood lymphocytes in vitro. Lymphocyte stimulation (auto-tumor stimulation ATS) in mixed lymphocyte tumor cell cultures (MLTC) and cytolysis in short term assays (autologous lymphocyte-mediated cytotoxicity ALC) were positive with cells of a proportion of sarcoma and carcinoma patients. In addition to the class I antigens, these tumors also carried the adhesion molecule ICAM-1. Monoclonal antibodies (MAb) to the MHC class I, but not to class II antigens inhibited lymphocyte proliferation in the MLTC and lysis of tumor cells in the ALC tests. In a proportion of originally negative or low expressor tumors, in vitro treatment with Interferon gamma and tumor necrosis factor alpha induced the expression of class I antigens and/or ICAM-1. In the MLTC the cytokine treated tumor cells stimulated the blood lymphocytes and generated cytotoxic effectors which reacted also with the untreated tumor cells.


Dual-Mode Organic Electrochemical Transistors Based on Self-Doped Conjugated Polyelectrolytes for Reconfigurable Electronics.
Reconfigurable organic logic devices are promising candidates for next generations of efficient computing systems and adaptive electronics. Ideally, such devices would be of simple structure and design, be power efficient, and compatible with high-throughput microfabrication techniques. This work reports an organic reconfigurable logic gate based on novel dual-mode organic electrochemical transistors (OECTs), which employ a self-doped conjugated polyelectrolyte as the active material, which then allows the transistors to operate in both depletion mode and enhancement mode. Furthermore, mode switching is accomplished by simply altering the polarity of the applied gate and drain voltages, which can be done on the fly. In contrast, achieving similar mode-switching functionality with other organic transistors typically requires complex molecular design or multi-device engineering. It in shown that dual-mode functionality is enabled by the concurrent existence of anion doping and cation dedoping of the films. A device physics model that accurately describes the behavior of these transistors is developed. Finally, the utility of these dual-mode transistors for implementing reconfigurable logic by fabricating a logic gate that may be switched between logic gates AND to NOR, and OR to NAND on the fly is demonstrated.


Experimental protocol of a randomized controlled clinical trial investigating the effects of personalized exercise rehabilitation on kidney transplant recipients' outcomes.
This randomized controlled trial (RCT) will investigate the effects of a personalized exercise rehabilitation regimen on return to work and find work rate, vascular health, functional capacity, quality of life, kidney function, and body composition in kidney transplant (KT) recipients. This RCT will recruit 120 men and/or women who have had a KT to participate in a 12 month exercise intervention or control (standard clinical care only) group. The 12 month exercise intervention will consist of one-on-one, progressive exercise rehabilitation sessions twice a week, for 60 min each session. The control group will continue standard clinical care as recommended by their post-transplant medical team without any intervention. The primary outcomes will be assessments of vascular structure and function, walking and strength measures to assess functional capacity, blood markers to assess kidney function, questionnaires to assess quality of life, DXA body scan to assess body composition, and a 1-week free living physical activity assessment. Additionally, employment status will be assessed. These assessments will be performed at baseline, 6 months, and 12 months. This investigation will increase the understanding of the role exercise rehabilitation has on managing the physiological and psychological health of the individual as well as on the individual's personal economic impact (via employment status). This study design has the potential to assist in constructing an effective exercise rehabilitation program that can be incorporated into part of standard post-transplant care.


The Design and Evaluation of Online Interactive Learning in an Undergraduate Nutrition Course.
Understanding factors that promote student engagement with online learning environments is important for benchmarking and improving the quality of teaching in a digital era. This study aimed to describe the online interactive content created for delivery of an undergraduate nutrition course and to evaluate student engagement with the online interactive content. We collected online questionnaire data in 2018 and 2019 from two cohorts of students enrolled in a Deakin University undergraduate nutrition unit. Two-sample unpaired t-tests were used to examine differences in participant engagement with online topic guides between static text-based and interactive content. A total of 89 participants (19-56 years) were included. Sixty four of students reported always/usually reading static text-based topic guides most weeks and 64% perceived them as moderately/highly effective. While 60% of participants reported reading the online interactive topic guides most weeks and 93% perceived them as moderate/highly effective. Most participants indicated the interactive topic guides were more effective than static text-based topic guides they experienced in other courses (76%). Hours dedicated to the online interactive topic guide were higher (6.4 SD 2.9 vs. 1.7 SD 1.7 h; P < 0.001) as was the rating of how engaging the topic guides were (7.2 SD 1.6 vs. 6.7 SD 2.5; P = 0.008). These findings suggest that interactive content is more engaging. However, this content may not be accessible to all students, and so familiarization and training prior to engaging in an interactive online unit may be needed.


Medical killing--an Evangelical perspective.
Evangelicals are unconditionally opposed to active euthanasia. Indirect euthanasia is seen as simply belonging to the risks inherent in any medical intervention. Passive euthanasia is accepted if used in order to save the dignity of the dying and is seen as merely ceasing to interfere with an irreversible dying process. The basis of evangelical ethics is the Bible supplemented by science and experience as a kind of natural law. Even though natural law comes under Biblical revelation, its acceptance is the reason for the similarity of the Evangelical and the Roman-Catholic position of Evangelicals. Evangelicals stress the necessity of a better counseling and investment for the deadly ill patient.


Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial.
High-fat meals induce postprandial inflammation. Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action. There is also an increasing body of evidence supporting the role of curcumin, a polyphenol from the curcuminoid family, as a modulator of proinflammatory processes. The objectives of this study were to investigate the following: 1) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal; and 2) the acute combined effects of this combination on the postprandial inflammatory response of subjects with abdominal obesity. In a double blind, crossover, randomized, placebo-controlled study, 11 men and 11 postmenopausal women [mean ± SD age: 62 ± 5 y; mean ± SD body mass index (in kg/m2): 29 ± 3] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1-2 wk: once after consumption of a dietary supplement (200 mg resveratrol and 100 mg curcumin, Res/Cur) and once after consumption of a placebo (cellulose). Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers, adhesion molecules, and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests. Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations. Supplementation with Res/Cur did not modify postprandial variations in circulating inflammatory markers (C-reactive protein, IL-6, IL-8, monocyte chemoattractant protein-1) and adhesion molecules [soluble E-selectin, soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1] compared to placebo (PTreatment×Time > 0.05). However, Res/Cur significantly decreased the cumulative postprandial response of sVCAM-1, compared to placebo (incremental area under the curve -4643%, P = 0.01). Postprandial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments. Acute supplementation with Res/Cur has no impact on the postprandial inflammation response to a high-fat meal in abdominally obese older adults. Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal. This trial was registered at clinicaltrials.gov as NCT01964846.


Dysglycemia and arrhythmias.
Disorders in glucose metabolism can be divided into three separate but interrelated domains, namely hyperglycemia, hypoglycemia, and glycemic variability. Intensive glycemic control in patients with diabetes might increase the risk of hypoglycemic incidents and glucose fluctuations. These three dysglycemic states occur not only amongst patients with diabetes, but are frequently present in other clinical settings, such as during critically ill. A growing body of evidence has focused on the relationships between these dysglycemic domains with cardiac arrhythmias, including supraventricular arrhythmias (primarily atrial fibrillation), ventricular arrhythmias (malignant ventricular arrhythmias and QT interval prolongation), and bradyarrhythmias (bradycardia and heart block). Different mechanisms by which these dysglycemic states might provoke cardiac arr-hythmias have been identified in experimental studies. A customized glycemic control strategy to minimize the risk of hyperglycemia, hypoglycemia and glucose variability is of the utmost importance in order to mitigate the risk of cardiac arrhythmias.


Competition and selectivity in supramolecular synthesis: structural landscape around 1-(pyridylmethyl)-2,2'-biimidazoles.
Three isomeric forms of 1-(pyridylmethyl)-2,2'-biimidazole, A1-A3, have been synthesized and subjected to systematic co-crystallizations with selected hydrogen- and halogen-bond donors in order to explore the impact of electrostatics and geometry on the resulting supramolecular architectures. The solid-state supramolecular behavior of A1-A3 is largely consistent in halogen-bonded co-crystals. Only two types of primary interactions, the N-HN/NH-N homomeric hydrogen-bond interactions responsible for the pairing of biimidazole moieties and the IN(pyridine) halogen bonds responsible for the co-crystal formation and structure extension, are present in these systems. The co-crystallizations with hydrogen-bond donors (carboxylic acids), however, lead to multiple possible structural outcomes because of the presence of the biimidazole-acid N-HO[double bond, length as m-dash]C/NH-O heterosynthon that can compete with biimidazole-biimidazole N-HN/NH-N homosynthon. In addition, the somewhat unpredictable nature of proton transfer makes the hydrogen-bonded co-crystals structurally less consistent than their halogen-bonded counterparts.


[A case of duplication of the common bile duct with anomaly of the intrahepatic bile duct].
A 50-year-old man, with a complaint of fever and epigastralgia, was admitted to the Yamaga City Hospital. Choledocholithiasis and stenosis of the lower part of choledochus were pointed out. Cholecystectomy, choledocholithotomy and papilloplasty were performed and the choledochotomy closed over a T-tube. T-tube cholangiograms, after operation, revealed stenosis, negative shadow and abnormal branching of the left intrahepatic bile duct. Then, the lateral segmentectomy of the liver was done. But the negative shadow didn't disappear . With further examination, we could find the accessory bile duct in the retroperitoneal space. Cholangiogram, from this accessory bile duct, revealed patency of this bile duct into the left intrahepatic bile duct and the duodenum. A final diagnosis of duplication of the common bile duct was established. We collected Japanese cases of this anomaly and discussed a classification of the disorder.


Marital interactions of male versus female alcoholics.
This study assessed the interactions of 131 alcoholic and nonalcoholic couples as they engaged in discussions of personally relevant problems. For 50 couples, the husband was alcoholic; for 15 couples, the wife was alcoholic; for 16 couples, both spouses were alcoholics; and for 50 couples, neither spouse was alcoholic. Observations were conducted during sessions when alcohol was consumed and in nondrinking sessions. Female alcoholic couples (with nonalcoholic spouses) demonstrated high negativity in the "no-drink" session, which was normalized in the drink session, suggesting an adaptive function to alcohol use. Concordant couples (both members were alcoholic) also demonstrated high negativity in the no-drink session, but exhibited increased negativity in the drink session, suggesting that concordance has a maladaptive impact on marital interaction. All alcoholic groups demonstrated greater negativity and lower positivity and congeniality in their marital interactions compared to nonalcoholic couples. Couples with male alcoholics were the least divergent from normal control couples. Unique female patterns in alcoholism are discussed in terms of adaptive and reinforcing patterns and spousal influences.


Modestobacter altitudinis sp. nov., a novel actinobacterium isolated from Atacama Desert soil.
Three presumptive Modestobacter strains isolated from a high altitude Atacama Desert soil were the subject of a polyphasic study. The isolates, strains 1G4T, 1G51 and 1G52, were found to have chemotaxonomic and morphological properties that were consistent with their assignment to the genus Modestobacter. They formed a well supported clade in Modestobacter 16S rRNA gene trees and were most closely related to the type strain of 'Modestobacter excelsi' (99.8-99.9% similarity). They were also closely related to the type strains of Modestobacter caceresii (99.6 % similarity), Modestobacter italicus (99.7-99.9% similarity), Modestobacter lacusdianchii (98.4-99.2% similarity), Modestobacter marinus (99.4-99.5% similarity) and Modestobacter roseus (99.3-99.5% similarity), but were distinguished from their closest relatives by a combination of phenotypic features. Average nucleotide identity and digital DNA:DNA hybridization similarities drawn from comparisons of draft genome sequences of isolate 1G4T and its closest phylogenetic neighbours mentioned above, were well below the threshold used to assign closely related strains to the same species. The close relationship between isolate 1G4T and the type strain of M. excelsi was showed in a phylogenomic tree containing representative strains of family Geodermatophilaceae. The draft genome sequence of isolate 1G4T (size 5.18 Kb) was shown to be rich in stress related genes providing further evidence that the abundance of Modestobacter propagules in Atacama Desert habitats reflects their adaptation to the harsh environmental conditions prevalent in this biome. In light of all of these data it is proposed that the isolates be assigned to a novel species in the genus Modestobacter. The name proposed for this taxon is Modestobacter altitudinis sp. nov., with isolate 1G4T (=DSM 107534T=PCM 3003T) as the type strain.


[Screening for active components of Sophorae Flos on inhibiting AGEs formation based on non-enzymatic glycation reaction].
Sugar-poison caused blood-heat is the pathological basis of many complications of diabetes. Advanced glycation end products( AGEs) are considered as the potential glycotoxic factor that can cause blood-heat. Sophorae Flos hold the effect of removing pathogenic heat from blood. In this study,chromatographic non-enzymatic glycation reaction system of bovine serum albumin( BSA)/methylglyoxal( MGO) and Sophorae Flos was established to identify active components in Sophorae Flos inhibiting AGEs formation. The HPLC was used to analyze chromatograms before and after the incubation of Sophorae Flos and methylglyoxal. Changes of chromatographic peaks of eight compounds was found. It is speculated that this change may be due to new substance produced by the reaction of active components in Sophorae Flos and methylglyoxal,and these active components may be flavonoid component rutin. Further investigation for the effects of rutin and MGO reaction( 1 ∶ 1,1 ∶ 3,3 ∶ 1) for 6 days on the formation of AGEs was performed. The results showed that the inhibition activity of rutin on AGEs production was most obvious when the reaction ratio was 1 ∶3,and the most inhibition was in 24 h and stabilized after 3 d. The product of the reaction of rutin with MGO was identified by LC-ESI-MS/MS,which indicated that the newly formed seven substances were the mono-and di-MGO adducts of rutin. This study showed that rutin is the active component on Sophorae Flos for removing pathogenic heat from blood by forming new compounds to inhibit the formation of sugar poison products,which provides reference for rational application of Sophorae Flos.


Nurses' documentation of physiological observations in three acute care settings.
To explore nurses' documentation of physiological observations in acute care; emergency department, medical and surgical units. In Australia, physiological observations include respiratory rate, oxygen saturation, heart rate, blood pressure, temperature and level of consciousness. There is a clear relationship between abnormal physiological observations and adverse events. Nurses have highest level of responsibility for accurate measurement, interpretation and documentation of physiological observations. A descriptive exploratory design was used and the study data were collected using a prospective point prevalence approach between 25 July 2012-22 August 2012. The study was conducted in the emergency department, two 30-bed medical units and one 30-bed surgical unit of a 578 bed public health service in Melbourne, Australia. All adult patients aged ≥18 years present during data collection periods were eligible for inclusion. Patients in the emergency department resuscitation area were excluded. Patient characteristics and physiological observations for the preceding 24 hours in ward patients or eight hours in emergency department patients were collected. One hundred and seventy-eight patients were included; 38 emergency department patients, 84 medical patients and 56 surgical patients. The median age was 72·5 years and 43·8% were males. The most frequently documented physiological observations were respiratory rate, oxygen saturation, heart rate and systolic blood pressure. The least frequently recorded physiological observations were temperature and conscious state. One or more abnormal physiological parameters was documented in 79·8% (n = 142) patients; evidence of reporting abnormalities was documented in 19·7% of patients (n = 28/142). When controlled for length of stay, physiological observations were more frequently documented in the emergency department. There was variability in the number of parameters documented and frequency of physiological observations documented by nurses. Physiological abnormalities that do not necessarily fulfil rapid response team activation criteria are common in acute care patients and provide nurses with an opportunity for early recognition of deteriorating patients.


[Accuracy of blood glucose self-monitoring in children with type-I diabetes].
Children with type I diabetes often believe that they are able do gauge their blood glucose value without measurement. This study investigated how accurate these estimates are and which of the patient characteristics might affect accuracy. Nineteen children with type I diabetes (age 7.3-17.3 years, duration of diabetes 0.1-12.0 years) estimated their blood glucose immediately before a blood glucose measurement by reflectance meter. Ten to 54 estimations and measurements were done by each individual during a summer camp. According to the method of Cox et al. accuracy of estimates was evaluated by error grid analysis. Five zones were defined: accurate estimates (zone A); clinically benign errors (zone B); clinically dangerous errors (zone C, D, E). An overall accuracy index was calculated by subtracting the summed percentage of estimates in zones C, D, E from the percentage in zone A. The mean percentage of estimates in zone A was 41.5 (10.0-75.0)%, the mean overall accuracy index was 9.8 (-47.4-62.5)%. Except for mean blood glucose which was inversely correlated with accuracy index (r = -0.53, P = 0.02) none of the other patient characteristics showed an effect on accuracy index. Accuracy of blood glucose estimates is lower in children with type I diabetes than in adults and varies substantially between individuals. High mean blood glucose values are associated with a lower accuracy of estimates.


Efficacy and safety of Qixue Tongzhi Granule in improving the exercise capacity of stable coronary artery disease: study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.
Despite optimal medical therapy, patients with stable coronary artery disease (SCAD) still have a high risk of recurrent cardiovascular events. Exercise capacity measured by cardiopulmonary exercise testing (CPET) is a good surrogate marker for the long-term prognosis of SCAD. Qixue Tongzhi Granule (QTG) is created by academician Chen Keji and has the function of tonifying qi, promoting blood circulation, and regulating qi-flowing. This trial aims to investigate the efficacy and safety of QTG in improving exercise tolerance, alleviating angina pectoris and anxiety/depression symptoms, promoting health-related quality of life, and reducing the risk of adverse cardiovascular events in subjects with SCAD. This is a randomized, double-blind, placebo-controlled trial. 150 SCAD patients with qi deficiency, blood stasis, and liver qi stagnation syndrome are enrolled. Patients will be randomly allocated to the QTG or placebo groups at a 1:1 ratio. QTG and placebo will be added to the modern guideline-directed medical therapy for 12 weeks and patients will be followed up for another 24 weeks. The primary outcome is the improvement of metabolic equivalents measured by CPET. The secondary outcomes are cumulative incidence of composite endpoint events, other indicators in CPET, changes in the Seattle Angina Questionnaire, traditional Chinese medicine syndrome scale, 12 items of Short Form Health Survey Questionnaire, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7, changes of ST-T segment in the electrocardiogram, improvement of left ventricular ejection fraction and left ventricular end-diastolic diameter in echocardiography. In addition, metabolomics analysis will be performed based on blood samples. Adverse events and safety evaluations will also be documented. A full analysis set, per protocol set, and safety analysis set will be conducted. This clinical trial can enrich treatment options for CHD patients with low cardiorespiratory fitness and psychological imbalance, and it may also create a new situation for promoting the application of traditional Chinese medicine in cardiac rehabilitation.Clinical Trial Registration: [http://www.chictr.org.cn], identifier: [ChiCTR2200058988].


Emergence of adaptive computation by single neurons in the developing cortex.
Adaptation is a fundamental computational motif in neural processing. To maintain stable perception in the face of rapidly shifting input, neural systems must extract relevant information from background fluctuations under many different contexts. Many neural systems are able to adjust their input-output properties such that an input's ability to trigger a response depends on the size of that input relative to its local statistical context. This "gain-scaling" strategy has been shown to be an efficient coding strategy. We report here that this property emerges during early development as an intrinsic property of single neurons in mouse sensorimotor cortex, coinciding with the disappearance of spontaneous waves of network activity, and can be modulated by changing the balance of spike-generating currents. Simultaneously, developing neurons move toward a common intrinsic operating point and a stable ratio of spike-generating currents. This developmental trajectory occurs in the absence of sensory input or spontaneous network activity. Through a combination of electrophysiology and modeling, we demonstrate that developing cortical neurons develop the ability to perform nearly perfect gain scaling by virtue of the maturing spike-generating currents alone. We use reduced single neuron models to identify the conditions for this property to hold.


Efficacy of the growing rod technique on kyphotic early-onset scoliosis.
To explore the application of the growing rod (GR) technique in the treatment of kyphotic early-onset scoliosis (KEOS) and analyze its surgical efficacy and safety. The clinical data of 30 children with KEOS who received GR treatment at our department between January 2016 and December 2019 were analyzed retrospectively. There were 18 cases with normal kyphosis (normal kyphosis group) and 12 cases with excessive kyphosis (excessive kyphosis group). Both groups received GR treatment, and all patients received anteroposterior and lateral spine X-ray examinations before, after the initial surgery, and at the final follow-up. The surgical conditions and imaging parameters of the two groups were compared, and the complications were recorded. There was no statistical difference in the Cobb angle of the major curve, apical vertebral translation (AVT), and trunk shift (TS) between the two groups before, after the first surgery, and at the final follow-up (P > 0.05). The Cobb angle of the major curve, the AVT, and the TS in both groups after the first surgery were lower than before the first surgery (P < 0.05), but there was no statistical difference between the two groups (P > 0.05). At the final follow-up, there were increases in both the Cobb angle and the AVT (P < 0.05), while the TS decreased in comparison with findings after the first surgery (P < 0.05). Before and after the first surgery and at the final follow-up appointment, there was a statistical difference in the degree of thoracic kyphosis (TK) between the two groups (P < 0.05), while there was no statistical difference in terms of lumbar lordosis (LL), the proximal junctional angle (PJA), and the distal junctional angle (DJA) (P > 0.05). After the first surgery, TK and LL showed a significant moderate response in both groups (P < 0.05), while there was no significant difference in TK, LL, PJA, and DJA compared with the results at the final follow-up (P > 0.05). The use of the GR technique can improve kyphosis in KEOS treatment.


Problems in intramedullary nailing of femoral fractures.
Intramedullary nailing, an improved method for treatment of fractures of the shaft of the femur, is still in a transitional stage. Experience in 35 cases indicates that supplementary fixation as safeguard against sepparation or overriding often is advisable, particularly in the presence of considerable fragmentation. Wire loops, cross screws and, in some cases, a Collins band modified in such a way as to avoid occlusion of blood supply, have been used for this purpose. For strength and rigidity, the rod used should be as great in diameter as the medullary space can accommodate. A method of preoperative determination of the size of rod to use has been devised. As the intramedullary rod may bend or break, it is advisable that patients be cautioned against full weight bearing on the injured leg too soon after operation.


A Comparative Analysis of the ADOS-G and ADOS-2 Algorithms: Preliminary Findings.
The Autism Diagnostic Observation Schedule (ADOS) is a widely utilized observational assessment tool for diagnosis of autism spectrum disorders. The original ADOS was succeeded by the ADOS-G with noted improvements. More recently, the ADOS-2 was introduced to further increase its diagnostic accuracy. Studies examining the validity of the ADOS have produced mixed findings, and pooled relationship trends between the algorithm versions are yet to be analyzed. The current review seeks to compare the relative merits of the ADOS-G and ADOS-2 algorithms, Modules 1-3. Eight studies met inclusion criteria for the review, and six were selected for paired comparisons of the sensitivity and specificity of the ADOS. Results indicate several contradictory findings, underscoring the importance of further study.


Arsenite removal from groundwater by iron-manganese oxides filter media: Behavior and mechanism.
Arsenic, a common contaminant in groundwater environments, usually coexists with other contaminants, for example, ammonium, iron, and manganese. In our previous studies, an iron-manganese (Fe-Mn) oxides filter media was developed for catalytic oxidation removal of ammonium, iron, and manganese. In this study, batch oxidation/adsorption kinetic experiments revealed that the filter media could easily oxidize arsenite (As(III)) to arsenate (As(V)). And the sorption kinetics was found to follow the pseudo-second-order kinetic model. X-ray powder diffraction (XRD) and Fourier transform infrared spectra (FTIR) along with X-ray photoelectron spectroscopy (XPS) were used to analyze the surface change in the Fe-Mn oxides. Based on sorption and spectroscopic measurements, the mechanism of As(III) removal by the Fe-Mn oxides filter media was found to be an oxidation coupled with sorption approach. As(III) in the aqueous solution was firstly oxidized to As(V) on the surfaces of the Fe-Mn oxides filter media. Then the converted As(V) was attracted to the Fe-Mn oxides filter media surfaces and bounded with the active sites (-OH groups), through weak intermolecular H-bondings. Our results indicated that the novel Fe-Mn oxides filter media could be applied for the simultaneous removal of ammonium, iron, manganese, and As(III) in drinking water treatment and environmental remediation. PRACTITIONER POINTS: A novel iron-manganese oxides filter for efficient As(III) removal was established. The exhausted filter media could be easily regenerated by NaHCO3 solution. Mn(III) related to surface lattice oxygen species was responsible for As(III) oxidation. The oxidation and adsorption processes were involved in As(III) removal. The filter media could be successfully applied to simultaneous removal of ammonium, manganese, iron, and arsenic.


Transcriptional regulation of the Pseudomonas aeruginosa iron-sulfur cluster assembly pathway by binding of IscR to multiple sites.
Iron-sulfur ([Fe-S]) cluster proteins have essential functions in many biological processes. [Fe-S] homeostasis is crucial for bacterial survival under a wide range of environmental conditions. IscR is a global transcriptional regulator in Pseudomonas aeruginosa; it has been shown to regulate genes involved in [Fe-S] cluster biosynthesis, iron homeostasis, resistance to oxidants, and pathogenicity. Many aspects of the IscR transcriptional regulatory mechanism differ from those of other well-studied systems. This study demonstrates the mechanisms of IscR Type-1 binding to its target sites that mediate the repression of gene expression at the isc operon, nfuA, and tpx. The analysis of IscR binding to multiple binding sites in the promoter region of the isc operon reveals that IscR first binds to the high-affinity site B followed by binding to the low-affinity site A. The results of in vitro IscR binding assays and in vivo analysis of IscR-mediated repression of gene expression support the role of site B as the primary site, while site A has only a minor role in the efficiency of IscR repression of gene expression. Ligation of an [Fe-S] cluster to IscR is required for the binding of IscR to target sites and in vivo repression and stress-induced gene expression. Analysis of Type-1 sites in many bacteria, including P. aeruginosa, indicates that the first and the last three AT-rich bases were among the most highly conserved bases within all analyzed Type-1 sites. Herein, we first propose the putative sequence of P. aeruginosa IscR Type-1 binding motif as 5'AWWSSYRMNNWWWTNNNWSGGNYWW3'. This can benefit further studies in the identification of novel genes under the IscR regulon and the regulatory mechanism model of P. aeruginosa IscR as it contributes to the roles of an [Fe-S] cluster in several biologically important cellular activities.


Biomechanical properties of bones from rats treated with sevelamer.
Sevelamer hydrochloride is used for ten years in patients on dialysis as a phosphate binder. We have previously shown that oral application of sevelamer prevents the bone loss and increases the bone volume in ovariectomized rats. In this study we further analysed the biomechanical properties of bones from rats treated with sevelamer utilizing a threepoint bending test to determine the mechanical properties of the cortical bone of the mid-shaft femur, while the indentation test was used to determine the mechanical properties of cancellous bone in the marrow cavity of the distal femoral metaphysis. Parameters analyzed included: maximum load (F(u)), stiffness (S), energy absorbed (W), toughness (T) and ultimate strength (sigma). The intrinsic properties, stress, elastic modulus and toughness were determined from measured maximum load, strains, stiffness, energy absorbed, outer and inner diameters, and calculated bone cross-sectional moment of inertia. Sevelamer was given to rats for 25 weeks with a content of 3% of sevelamer in a standard diet, starting immediately following ovariectomy (OVX). Animals were divided to the following groups: (1) Sham; (2) Sham + sevelamer 3%; (3) OVX; (4) OVX + sevelamer 3%. Our results showed that sevelamer particularly influenced the rat trabecular bone by increasing the maximum load for 26.2%, energy absorbed for 24.2% and the ultimate strength for 26.2% in sham animals treated with sevelamer 3%, as compared to sham rats. Sevelamer 3% in OVX rats also increased the maximum load for 71.4%, stiffness for 70.7%, energy absorbed for 55.9% and the ultimate strength for 71.3% as compared to OVX controls. In the three bending test sevelamer had a very little effect on preventing loss of bone strenght in the cortical bone. These results collectively suggest that sevelamer improves bone biomechanical properties, mainly affecting trabecular bone quality in both normal and ovariectomized rats.


Neurodevelopmental markers in different psychopathological dimensions of first episode psychosis: the ESPIGAS study.
The main aim of this study was to explore whether specific groups of patients with first episode non-affective psychosis could be identified on a psychopathological basis and, then, whether such identified groups could be validated by exploring their correlation with a variety of neurodevelopmental markers. Eighty-seven patients with a first episode of non-affective psychotic disorder were consecutively recruited. We assessed psychopathology and neurological soft signs using the PANSS and the Neurological Evaluation Scale, respectively. We collected information on obstetric complications, premorbid adjustment and family history. All PANSS symptoms were analysed using principal component analysis and four factors were obtained (negative, disorganization, positive and paranoid). Subsequently, the four factors were subjected to a cluster analysis where three groups emerged: "paranoid" (n=40), "low score" (n=29) and "negative" (n=18) subtype. After adjusting by sex and age, we found that the "negative group" had poorer social premorbid adjustment, worse verbal fluency and higher prevalence of both obstetric complications and neurological soft signs, when compared with the "low score" group. Similarly, the "negative group" showed significantly poorer social premorbid adjustment and higher number of neurological soft signs than the "paranoid group". Our results support that, among non-affective first onset psychotic patients, those with predominant negative symptoms are more likely to correlate with higher presence of neurodevelopmental markers.


Role of Increased Lipoprotein (a) in Retinal Vein Occlusion: A Systematic Review and Meta-analysis.
Background Increased lipoprotein (a) [Lp(a)] has been associated with enhanced risk of cardiovascular events and more recently with venous thromboembolism. However, there is inconclusive data on the association between enhanced Lp(a) and retinal vein occlusion (RVO). We aimed to assess the role of Lp(a) in RVO. Methods We performed a systematic review and meta-analysis of the studies addressing the role of Lp(a) in RVO. A systematic literature search was performed to identify all published papers reporting Lp(a) levels. Main outcome measures consisted of Lp(a) levels in patients with (cases) or without (controls) RVO. Results We included 13 studies for a total of 1,040 cases and 16,648 controls. Lp(a) levels above normal limits were associated with RVO (OR 2.38, 95% CI 1.7-3.34) and patients with RVO had higher Lp(a) levels than controls (weighted mean difference: 13.4 mg/dL, 95% CI 8.2-18.6). Conclusion Increased Lp(a) levels associate with RVO and should be included among diagnostic and prognostic indexes for this unusual-site vein thrombosis. Therapeutic interventions aimed to lower Lp(a) should be tested in RVO patients.


[Of the Hôtel des invalides at the imperial court. Careers of Maloet father and son, doctors regents of the Medical College of Paris at the 18th century].
Although the names of the 18 Century's doctors of Medicine are not unknown, no essay was really written about them and this paper tends to attract attention to the Parisian medical elite of the Ancient System. Pierre Maloet is the example of the doctor of the Monarchical system who as a doctor from Montpellier registered in the Paris Faculty at the beginning of the Century and thanks to his relations with the Guyard-Duchenne managed to be introduced into the Court and the military world. Maloets' careers are good illustrations of penetration into the society and onto the domain of the great varieties of medical exercises. Never they publicly claimed the new ideas of the Century of Enlightment but they embodied its contradictions into the attachment to old structures and the will of innovation.


The Nucleic Acid Database.
The Nucleic Acid Database was established in 1991 as a resource to assemble and distribute structural information about nucleic acids. Over the years, the NDB has developed generalized software for processing, archiving, querying and distributing structural data for nucleic acid-containing structures. The architecture and capabilities of the Nucleic Acid Database, as well as some of the research enabled by this resource, are presented in this article.


Topical astragaloside IV-releasing hydrogel improves healing of skin wounds in vivo.
Topical delivery of therapeutic agents at the time of injury to accelerate skin repair and prevent the formation of scars during the wound healing process has received increasing attention and represents a novel regenerative and prophylactic strategy for wound treatment. The aim of this study was to invesigate, for the first time, the influence of topical astragaloside IV-releasing hydrogel on the wound repair and regeneration. Using the sodium alginate-gelatin as a hydrogel vehicle, the astragaloside IV was incorporated into the topical carrier and kept releasing with a sustained manner at the wound site. With the rat skin excision model, regulation of the astragaloside IV hydrogel on the wound repair and regeneration were investigated. It was found that the astragaloside IV hydrogel was effective in the skin wound repair, leading to a significant improvement on the wound closure, collagen synthesis and skin tensile strength recovery. Meanwhile, for the first time, that functions of astragaloside IV hydrogel in activating the skin appendages regeneration and increasing the transforming growth factor-β(1) (TGF-β(1)) level in serum were shown. Results of this study provided evidence for the alginate-gelatin hydrogel as efficient carrier for the topical delivery of bioactive molecules to the injured site. The astragaloside IV releasing hydrogel was shown a promising therapeutic formulation for wound healing, as well as its regenerative feature and underlying mechanism contribute to the skin regeneration were disclaimed.


Pediatric hospitalist comanagement of surgical patients: structural, quality, and financial considerations.
Comanagement of surgical patients is occurring more commonly among adult and pediatric patients. These systems of care can vary according to institution type, comanagement structure, and type of patient. Comanagement can impact quality, safety, and costs of care. We review these implications for pediatric surgical patients.


Identification of promising strategies to sustain improvements in hospital practice: a qualitative case study.
A quality improvement collaborative is an intensive project involving a combination of implementation strategies applied in a limited "breakthrough" time window. After an implementation project, it is generally difficult to sustain its success. In the current study, sustainability was described as maintaining an implemented innovation and its benefits over a longer period of time after the implementation project has ended. The aim of the study was to explore potentially promising strategies for sustaining the Enhanced Recovery After Surgery (ERAS) programme in colonic surgery as perceived by professionals, three to six years after the hospital had successfully finished a quality improvement collaborative. A qualitative case study was performed to identify promising strategies to sustain key outcome variables related to the ERAS programme in terms of adherence, time needed for functional recovery and hospital length of stay (LOS), as achieved immediately after implementation. Ten hospitals were selected which had successfully implemented the ERAS programme in colonic surgery (2006-2009), with success defined as a median LOS of 6 days or less and protocol adherence rates above 70%. Fourteen semi-structured interviews were held with eighteen key participants of the care process three to six years after implementation, starting with the project leader in every hospital. The interviews started by confronting them with the level of sustained implementation results. A direct content analysis with an inductive coding approach was used to identify promising strategies. The mean duration of the interviews was 37 minutes (min 26 minutes - max 51 minutes). The current study revealed strategies targeting professionals and the organisation. They comprised internal audit and feedback on outcomes, small-scale educational booster meetings, reminders, changing the physical structure of the organisation, changing the care process, making work agreements and delegating responsibility, and involving a coordinator. A multifaceted self-driven promising strategy was applied in most hospitals, and in most hospitals promising strategies were suggested to sustain the ERAS programme. Joining a quality improvement collaborative may not be enough to achieve long-term normalisation of transformed care, and additional investments may be needed. The findings suggest that certain post-implementation strategies are valuable in sustaining implementation successes achieved after joining a quality improvement collaborative.


Pathological study of splenomegaly associated with cadmium-induced anemia in rats.
Splenomegaly was observed both in male and female Sprague-Dawley rats after 1 week of exposure to CdCl2 (0.6 mg Cd/kg/day). Spleen weight reached about double that in controls by 8 weeks of Cd exposure. Histopathological examination of the enlarged spleen revealed that iron- and lipid-laden histiocytes were clustered in the periarterial lymphatic sheath, and the red pulp appeared to be expanded. It is noteworthy that electron microscopy revealed marked poikilocytosis and Heinz body formation in red blood cells (RBCs) in both the sinus and cord. Histiocytes were swollen by a granular substance in the cytoplasm and also many secondary lysosomes. These morphological findings indicate that degradation of damaged RBCs induced by exposure to Cd might be promoted in the spleen and possibly cause splenomegaly. This RBC damage-hemolysis-splenomegaly sequence is also considered to be associated with the etiology of Cd-induced anemia. In addition to the abnormal RBC degradation, nuclei of lymphocytes in the Cd-exposed spleen exhibited high electron density, consistent with a preapoptotic state suggesting the immunosuppressive effect of Cd.


Adverse effects of the SSRI antidepressant sertraline on early life stages of marine invertebrates.
Widespread contamination of coastal environments by emerging compounds includes low concentrations of pharmaceuticals. These pollutants are not currently incorporated in monitoring programs despite their effects on non-target organisms are very little documented. Among the selective serotonin reuptake inhibitor (SSRI) antidepressants, sertraline (SRT) is one of the most prescribed globally. In this work, earlier life stages of Amphibalanus amphitrite, Brachionus plicatilis and Mytilus galloprovincialis were exposed to environmental concentrations of SRT in order to study both sub-lethal and lethal responses in 24/48 h-tests. Low concentrations of SRT altered significantly swimming behavior in A. amphitrite and B. plicatilis giving 48 h-EC50 (μg/L) of 113.88 and 282.23, respectively whereas higher values were observed for mortality and immobilization. EC50 embryotoxicity with M. galloprovincialis was 206.80 μg/L. This work add new data about SRT ecotoxicity on marine invertebrates and confirms the applicability of behavioral endpoints to evaluate the environmental impact of antidepressants in marine organisms.


Serratia corneal ulcers: a retrospective clinical study.
To study the clinical and microbiological profile of Serratia corneal ulcers at the Cornea Service of the Wills Eye Hospital. This was a retrospective, observational case series. The clinical records of patients with Serratia marcescens corneal ulcers seen at the Cornea Service of the Wills Eye Hospital between January 1, 1998 and December 31, 2002 were reviewed. Twenty-four cases of Serratia keratitis were identified in 21 patients. Two patients (9.5%) had recurrent keratitis, 1 of which recurred twice. Both had corneal graft edema and were on topical steroids and antiglaucoma drops. The Serratia infection in 15 patients (71%) was associated with an abnormal corneal surface. Twelve of these patients (57%) had the ulcer in a corneal graft, 4 (19%) of which were associated with suture infiltrates. Fifteen patients (71%) were on topical medications-15 used corticosteroids and 13 used antiglaucoma drops. Six patients (29%) were contact lens wearers-1 had a concomitant suture infiltrate associated with a corneal graft, and 5 had otherwise healthy corneas. One isolate lacked in vitro susceptibility to ciprofloxacin and ofloxacin but was susceptible to gentamicin and tobramycin. Nineteen patients had a favorable response to medical therapy. Two patients with poor outcome had large corneal ulcers with severe necrosis and thinning associated with delay in treatment. Serratia marcescens keratitis is associated with the presence of an abnormal corneal surface, use of topical medications, and contact lens wear. Prompt medical therapy results in a good clinical response in the majority of cases.


[Perception of organizational climate and burnout amongst health care workers: the role of alexithymia as a moderator].
This paper reports a study on 238 health care workers from an hospital in central Italy. We examined: 1) how some dimensions regarding perceived quality of the organizational and relational climate (social warmth and quality of working life both in the ward and in the organization) influence various indicators of burnout (emotional exhaustion, depersonalization, personal accomplishment); 2) if it was possible to improve the previous regressive models by including the personality construct, alexithymia. Controlling for age and gender, results of the hierarchical regression showed significant two-way interactions between organizational/relational climate and alexithymia in predicting emotional exhaustion (p = .005 for both the ward and the organization) and personal fulfillment (for ward, p = .020; for perceived relational climate, p = .037). Depersonalization was accounted by the main effect of alexithymia (p = .000). In conclusion, results demonstrate the need to include the alexithymia construct in models predicting the various dimensions of burnout.


NAG-1 up-regulation mediated by EGR-1 and p53 is critical for quercetin-induced apoptosis in HCT116 colon carcinoma cells.
Quercetin, a flavonoid molecule ubiquitously present in nature, has multiple effects on cancer cells, including the inhibition of cell proliferation and migration. However, the responsible molecular mechanisms are not fully understood. We found that quercetin induces the expression of NAG-1 (Non-steroidal anti-inflammatory drug activated gene-1), a TGF-beta superfamily protein, during quercetin-induced apoptosis of HCT116 human colon carcinoma cells. Reporter assays using the luciferase constructs containing NAG-1 promoter region demonstrate that early growth response-1 (EGR-1) and p53 are required for quercetin-mediated activation of the NAG-1 promoter. Overexpression of NAG-1 enhanced the apoptotic effect of quercetin, but suppression of quercetin-induced NAG-1 expression by NAG-1 siRNA attenuated quercetin-induced apoptosis in HCT116 cells. Taken together, the present study demonstrates for the first time that quercetin induces apoptosis via NAG-1, providing a mechanistic basis for the apoptotic effect of quercetin in colon carcinoma cells.


Studies on the muscle relaxation effects of ethyl loflazepate (CM6912) and evaluation as an anti-anxiety drug.
A new anti-anxiety drug, CM6912 (ethyl loflazepate, ethyl 7-chloro-2,3-dihydro-5-(2-fluorophenyl)-2-oxo-1H-1,4-benzodiazepine-3- carboxylate), was investigated for its effects on the alpha- and gamma-motor systems and on the cooperative muscular motions and for its interactions with other CNS drugs. The results obtained are as follows: Muscular discharges (EMG) induced by decerebrate rigidity were unaffected by 10 mg/kg (p.o.) of CM6912, but the amplitudes of the EMG were reduced by 50% for 3 hr by 30 mg/kg of CM6912 at 30 min after administration. Diazepam (10 mg/kg) also decreased the amplitudes of the EMG even at 5 min after administration, indicating that diazepam had a stronger than CM6912. Both monosynaptic spinal reflex (MSR) and polysynaptic spinal reflex (PSR) were unaffected by CM6912 (100 mg/kg). Dorsal root reflex potential was slightly enhanced by CM6912 (100 mg/kg), but not at a dose of 30 mg/kg. Diazepam (10 mg/kg) did not decrease MSR, but slightly reduced PSR. Dorsal root reflex potential was almost doubled by diazepam. The frequency of spontaneous discharges of Gla spindle afferent fiber of the extensor muscle of the hindlimb of anesthetized cats was unchanged by 10 mg/kg CM6912, but was suppressed by diazepam at the same dose while at a dose of 30 mg/kg, it was reduced mildly by CM6912, and markedly by diazepam. ED50 values for the antagonistic action on bemegride-induced convulsions were 0.30 mg/kg for CM6912 and 0.49 mg/kg for diazepam at 1 hr after administration, and they were 0.30 mg/kg and 0.67 mg/kg for CM6912 and diazepam, respectively, at 4 hr. The potentiating action of CM6912 on chlorprothixene-induced anesthesia was far weaker than that of diazepam. The suppressive potency of CM6912 on the adaptability to the rotarod was about half that of diazepam, and the muscle relaxant action of CM6912, examined by the inclined board test and the hanging test, was found to be similar to that of diazepam. These results suggest that CM6912 is less potent than diazepam in reducing muscular tone and in inducing sleep, while it has a stronger and longer-lasting anti-anxietic activity than diazepam.


Rita Levi-Montalcini: the discovery of nerve growth factor and modern neurobiology.
The remarkable accomplishments in developmental neurobiology within the past 60 years have depended on two things: (i) a succession of original histochemical and immunohistochemical methodologies for identifying pathways in the nervous system with increasing precision and sensitivity, and (ii) the discovery of growth factors for neurons. Growth factors are naturally occurring, essential biological mediators that promote cell growth, differentiation, survival and function in specific nerve cell populations. The discovery of nerve growth factor (NGF) by Rita Levi-Montalcini in the 1950s represents an important milestone in the processes that led to modern cell biology. NGF was the first growth factor identified, for its action on the morphological differentiation of neural-crest-derived nerve cells. Later, its effect on neuronal cells of the peripheral and central nervous systems, and on several non-neuronal cells was also determined. Thus, Levi-Montalcini's work on NGF represents, as acknowledged by the Nobel Prize Assembly in its press release of 13 October 1986, "a fascinating example of how a skilled observer can create a concept out of apparent chaos".