Biocontamination and diversity of epilithic bacteria and fungi colonising outdoor stone and mortar sculptures.
Microbial communities colonising outdoor sculptures form intricate and dynamic ecosystems, which can accelerate the deterioration processes of the artworks and pose challenges to their conservation. In this study, the bacterial and fungal communities colonising the surfaces of five contemporary outdoor sculptures were characterised by high-throughput sequencing. The sculptures, made of marble, granite, Ançã limestone and mortar, are in urban parks and squares in the district of Porto, Portugal. The analysis of the microbial populations revealed great taxonomic diversity and species richness, including in well-preserved sculptures showing few visible traces of contamination. Proteobacteria, namely the genera Pseudomonas and Sphingomonas, were the core taxa common to all the sculptures, while Massilia and Aureobasidium were dominant only in granite. An abundance of pigment-producing microorganisms, such as Deinococcus, Methylobacterium, Rhodotorula and Sporobolomyces, was also found in granite. These are relevant taxonomic groups that can negatively impact stone and mortar artworks. The study was complemented with colourimetric analyses and bioluminescence assays to measure the adenosine triphosphate (ATP) content of samples collected from specific contaminated areas of the sculptures. The characterisation of the microbiomes of sculptures can provide further knowledge on the deterioration risks of this type of artwork in the region and help outline future targeted conservation strategies. KEY POINTS: • Rich and abundant microbiomes expose sculptures' vulnerability to deterioration. • Well-preserved sculptures are at risk of deterioration by pigment-producing taxa. • ATP and colourimetry quickly identified the most relevant contaminated areas.


LongHest project: A prospective, observational study of extended half-life treatment in the musculoskeletal health of patients with severe haemophilia A.
Prophylactic treatment is the gold standard in the treatment of patients with haemophilia. Prophylaxis with extended half-life (EHL) treatment has shown long-term safety and efficacy in patients with haemophilia. To evaluate the efficacy of prophylaxis with EHL treatment in the frequency of haemarthrosis and musculoskeletal health in adult patients with severe haemophilia A. Prospective cohort study. Forty-six patients with severe haemophilia A were recruited. The frequency of haemarthrosis (self-reports), joint condition (Haemophilia Joint Health Score), pain intensity (visual analogue scale), range of motion (goniometry), and strength (dynamometry) and muscle activation (surface electromyography) were evaluated. Three assessments were carried out: at baseline (T0), at 6 months (T1) and at 12 months following treatment (T2). There were significant changes in the within-subject effect in the frequency of haemarthrosis in elbow (F(1.05;96.20) = 3.95; P < .001) and knee (F(1.73;157.99) = 9.96; P < .001). Significant within-subject effect in elbow pain intensity (F(2;182) = 63.51; P < .001) was found. The mean values of the frequency haemarthrosis in elbow (from .66±1.01 to .04±.20) and knees (from .55±.68 to .33±.53) decrease after the period study. The intensity of elbow pain and (from 3.08±1.69 to 2.67±1.73), decrease after the 12-month follow-up period. Prophylaxis with extended half-life treatment reduces the frequency of haemarthrosis in elbow and knee in adult patients with haemophilia. EHL treatment reduces the intensity of elbow pain in patients with haemophilic arthropathy.


[Pneumocystis carinii pneumonia in HIV infections. Committee of the 1st Consensus Conference of anti-infectious therapy organized in May 1990 in Paris by the Société de Pathologie Infectieuse de Langue Française].
At the end of the first consensus conference on anti-infectious therapy organized by the French Language Society of Infectious Pathology in May 1990 and devoted to pneumocystosis in patients with human immunodeficiency virus (HIV) infection, the consensus committee produced this paper which answers the following 4 questions: what are the indications, technical requirements, sensitivity and benefits of induced expectoration in the diagnosis of Pneumocystis carinii pneumonia? what are the initial and secondary severity factors; in which cases is transfer to an intensive care unit indicated; in which manner can treatment be modified? what is the position occupied by corticosteroid therapy in the management of pneumocystosis? when is prophylaxis of pneumocystosis indicated; what prophylactic methods are used and how to choose among them?


Potentiation of the PFC response to thymus-independent antigens by heterologous erythrocytes.
Immunization with horse erythrocytes (HRBC) and a thymus-independent (TI) antigen of the TI-2 category, such as a native dextran, dinitrophenyl-dextran (DNP-dextran), or DNP-Ficoll, resulted in a three- to four-fold enhancement of the plaque-forming cell response to the TI antigen. The effect was found to be T-cell associated, since cyclosporin A abrogated enhancement. The T cells of T-cell factor involved were elicited early in the response to HRBC and acted on the initial stages of the TI response. The HRBC-induced potentiation affected only B cells activated by the TI antigen; it could not induce a TI response when TI-2 antigen was given under nonresponsive conditions; and it had only a slight effect on the response to a thymus-dependent (TD) antigen. A soluble TD antigen, bovine serum albumin-coupled dextran (BSA-dextran), did not have potentiating ability equivalent to that of the particulate HRBC. It was concluded that non-specific T-cell help can influence TI-2 responses when they are present simultaneously.


Illness Stigma, Worry, Intrusiveness, and Depressive Symptoms in Youth With Inflammatory Bowel Disease.
Youth who experience IBD-associated stigma may manifest increased worry about aversive symptoms that can intrude on their participation in routine activities (eg, school, social events), potentially resulting in limited opportunities for reinforcement and increased depressive symptoms. The present study examined an IBD stigma → IBD worry → illness intrusiveness → depressive symptoms serial mediation model, in which stigma was hypothesized to confer an indirect effect on youth depressive symptoms through the serial effects of stigma on IBD worry and illness intrusiveness. Youth with IBD (N = 90) between the ages of 10 and 18 years were recruited from a pediatric gastroenterology clinic and completed measures of IBD stigma, IBD worry, illness intrusiveness, and depressive symptoms. In addition to several independent direct effects among the modeled variables, results revealed a significant IBD stigma → IBD worry → illness intrusiveness → depressive symptoms serial mediation path (effect = 0.63, 95% CI = 0.22 to 1.20), controlling for youth sex and IBD severity. The experience of IBD-related stigma may prompt increased worry about IBD symptoms, independent of the influence of disease activity. Further, heightened worry appears to amplify youths' experience of IBD-imposed limitations on routine and rewarding activities, increasing their risk for experiencing depressive symptoms. Our findings highlight the importance of regular screening for depressive symptoms, as well as the identification of potential risk factors associated with emotional adjustment difficulties. Stigma-specific treatment modules could be integrated within existing cognitive-behavioral approaches for reducing worry and depressive symptoms in youth with IBD.


Effect of buffer composition and preparation protocol on the dispersion stability and interfacial behavior of aqueous DPPC dispersions.
The effect of the buffer composition and the preparation protocol on the dynamic surface tension (DST) and vesicle sizes of aqueous dipalmitoylphosphatidylcholine (DPPC) dispersions was studied. Four isotonic buffers were used in preparing DPPC dispersions at physiological conditions for possible biological applications: (1) a standard PBS solution; (2) the above PBS with 1mM CaCl(2); (3) PBS with one tenth the previous standard phosphate salt concentrations and 2.5 mM CaCl(2); and (4) 150 mM NaCl with 2.5 mM CaCl(2) and 10mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid). Two protocols, with a new method and an old method (Bangham method), were used in preparing the DPPC dispersions. The DPPC dispersions prepared with the new method contained mostly vesicles and were quite stable at 25 or 37 degrees C. Dynamic light scattering (DLS) and spectroturbidimetry (ST) results showed that the DPPC vesicle sizes in buffer (4) were much smaller than those in the other buffers. When the DPPC dispersions were prepared with the new method, the diameter of the DPPC particles was smaller than those with the old method. The DPPC vesicles with the new method were more stable than those with the other method. The DPPC dispersions of 1000 ppm at 37 degrees C with the new method produced, at pulsating area conditions at 20 cycles per minute, low tension minima (gamma(min)), lower than 10 mN/m, in buffers (1), (2), and (4). With buffer (4) the DSTs were lower and were achieved faster than with the other buffers. A minimum concentration of 1000 or 250 ppm DPPC was needed to produce DSTs lower than 10 mN/m within 10 min or less, with buffer (2) or (4), respectively. IRRAS results suggest that DPPC in buffer (2) or (4) forms a close-packed monolayer at the interface. These results have implications for designing efficient protocols of lipid dispersion preparation and lung surfactant replacement formulations in treating respiratory disease.


Five early milestones in premature infants.
The onset of five early milestones was studied in premature and full-term infants. The milestones are: recognition of mother's voice and face, 3-month smile, following through 180 degrees, and two hand-eye coordination. It was hypothesized that premature infants would show delay in acquiring milestones related to time separated from mother. Compared to full-term infants, the prematures had a significant difference in the means only for the onset of smiling, and no effect related to maternal separation.


The impact of liver disease on health-related quality of life: a review of the literature.
Quality of life as an outcome variable has become an important measure in clinical research. Making a transition from a "biomedical model" of health to one that incorporates the social aspects of disease, clinicians and researchers dealing with chronic illness now incorporate quality-of-life measures into clinical practice and research. Chronic liver disease has shown a significant impact on the well-being of patients and contributes to the significant morbidity associated with these conditions. In this article, we review the recent research that has examined the impact of chronic liver disease on health-related quality of life.


Effects of agents that modulate potassium permeability on smooth muscle cells of the guinea-pig basilar artery.
1 Effects of various chemical agents, with known actions on K-permeability, on the membrane potential, membrane resistance and spike activity of smooth muscle cells of the guinea-pig basilar artery were investigated using the microelectrode method. The K-permeability suppressing agents procaine, tetraethylammonium (TEA), 4-aminopyridine (4-AP), and the K-permeability increasing agents acetylcholine (ACh), caffeine and 2-nicotinamidoethyl nitrate (2-NN) were used.2 The mean resting membrane potential of smooth muscle cells was -50.6 mV and was electrically quiescent. The maximum slope of the membrane depolarization produced by a ten fold increase in [K](o) plotted on a log scale was 42 mV. The contribution of the Na-K pump mechanism to the membrane potential was apparent, i.e. the maximum hyperpolarization induced by activation of the Na-K pump was -71 mV. This hyperpolarization ceased following application of ouabain. Reduction in the [Na](o) slightly hyperpolarized the membrane.3 TEA (1-10 mM) and procaine (0.3-10 mM) depolarized the membrane dose-dependently, and increased the membrane resistance. TEA markedly inhibited and procaine slightly inhibited rectification of the membrane.4 Caffeine had dual actions on the membrane potential, i.e. a low concentration (below 1 mM) hyperpolarized the membrane and reduced the membrane resistance, while increased concentrations (above 1 mM) transiently hyperpolarized, and then depolarized the membrane with an increase in the membrane resistance.5 ACh hyperpolarized the membrane dose-dependently (10(-7)-10(-5)M), and reduced the membrane resistance. The hyperpolarizing action of ACh did not persist and even in the presence of ACh, the membrane was repolarized to near the control level.6 2-NN (up to 10(-4)M) and 4-AP (up to 1 mM) did not modify the membrane potential or the membrane resistance.7 TEA (10 mM) generated a spike either spontaneously or by application of electrical stimulation and the spike was preceded or followed by slow oscillatory potential changes. These potential changes ceased with application of diltiazem (10(-5)M).8 Low concentrations of procaine (below 1 mM) accelerated but high concentrations (5-10 mM) inhibited the spike generation in the presence of 10 mM TEA. Low concentrations of caffeine (below 1 mM) inhibited the spike generation and higher concentrations (above 1 mM) of caffeine accelerated the spike generation in the presence of 10 mM TEA. ACh (10(-6)-10(-4)M) consistently inhibited the spike generation, with 10 mM TEA pretreatment.9 4-AP (1 mM) did not modify the membrane potential yet accelerated the spike generation, in the presence of 10 mM TEA. 2-NN (10(-4)M) had no effect on the spike evoked in the presence of 10 mM TEA.10 The results show that the low membrane potential in smooth muscle cells of the guinea-pig basilar artery is mainly due to the low permeability of the membrane to K ion, presumably due to the lack of a K channel sensitive to 2-NN and 4-AP. Similarities and differences between this vascular tissue and other regions are also discussed.


Rating scales for mania: is self-rating reliable?
This commentary addresses the issue of whether self-rating mania scales are reliable. After a brief introduction, several newly developed self-rating mania scales are described and critically reviewed. Among the issues discussed are: the practical utility of self-assessment in patients with mania; the influence of severity of illness on ability to self-report; and, the extent to which the presence of psychosis or the absence of insight significantly interferes with a patients' ability to reliably complete self-rating measures. Data from recent studies suggests that self-rating mania scales are both reliable and valid for patients with manic symptoms, including those with psychotic features and those having little or no insight into their illness. The merits of including self-rating measures in the assessment of mania are discussed in terms of their value for both clinical and research purposes.


Antibody-based detection of acid-shocked, acid-adapted, and apple juice-incubated Escherichia coli O157:H7.
Sandwich enzyme-linked immunosorbent assays (sELISA) allow for rapid detection of Escherichia coli (E. coli) O157:H7. Acidic conditions similar to those in certain foods and juices may reduce the ability to detect E. coli O157:H7. Growth of E. coli O157:H7 at pH 4 compared to pH 5-7 reduced fluorescent signal at the lower bacterial concentrations without altering the range of detection. Both acid-adaptation and a subsequent pH 7 incubation reversed sensitivity. Incubation in apple juice was not deleterious to sELISA detection. Exposure to acidic conditions can cause a small reduction in sELISA sensitivity used to detect E. coli O157:H7.


Immunoglobulin G4-associated de novo autoimmune hepatitis after liver transplantation for chronic hepatitis B- and C-related cirrhosis and hepatocellular carcinoma: a case report with literature review.
Immunoglobulin G4 (IgG4)-associated autoimmune hepatitis (AIH) was recognized as a new disease entity; however, IgG4-associated de novo AIH after the liver transplantation had not been reported yet. Herein we have described a 56-year-old man who developed IgG4 de novo AIH as 1 year-post liver transplantation after receiving pegylated interferon alpha-2a and ribavirin therapy for hepatitis C virus recurrence. The histopathologic evidence showed an aggressive lymphoplasmacytic interface hepatitis with centrilobular necrosis (plasma cells > 30%) and IgG4-positive plasma cells (>10 per high power field). Serum IgG (9220 mg/dL) and IgG4 (3289 mg/dL) were also elevated. Improvement of liver function tests (LFTs) by prednisone and azathioprine therapy are manifested as normalized alanine aminotransferase and IgG levels. IgG4 relates to more severe histological activity; however, it is believed to be a good prognostic predictor of a response to prednisone plus azathioprine therapy especially with early diagnosis and timely management.


Prognostic significance of myocardial ischemia by dobutamine stress echocardiography in patients without angina pectoris after coronary revascularization.
The clinical utility of stress testing in patients without angina pectoris after revascularization has been questioned. Dobutamine stress echocardiography (DSE) is an established technique for detection of myocardial ischemia and cardiac risk stratification. We studied the prognostic value of DSE in 393 patients without typical angina pectoris after coronary revascularization. Ischemia was incremental to clinical data in predicting all-cause death (hazard ratio 3.5, 95% confidence interval 1.8 to 6.7) and cardiac death (hazard ratio 4.2, 95% confidence interval 1.8 to 9.8). In conclusion, myocardial ischemia during DSE is independently associated with an increased risk of all-cause mortality and cardiac death in these patients after adjustment for clinical data.


Seeing stem cells at work in vivo.
Stem cell based-therapies are novel therapeutic strategies that hold key for developing new treatments for diseases conditions with very few or no cures. Although there has been an increase in the number of clinical trials involving stem cell-based therapies in the last few years, the long-term risks and benefits of these therapies are still unknown. Detailed in vivo studies are needed to monitor the fate of transplanted cells, including their distribution, differentiation, and longevity over time. Advancements in non-invasive cellular imaging techniques to track engrafted cells in real-time present a powerful tool for determining the efficacy of stem cell-based therapies. In this review, we describe the latest approaches to stem cell labeling and tracking using different imaging modalities.


Size, gender, and sex change in dwarf ginseng,Panax trifolium (Araliaceae).
Flowering individuals of dwarf ginseng may be either male or hermaphroditic. I recorded the sex expression and size of individuals in three populations for three or four years in order to 1) determine whether this bimodal distribution of sex expression was due to sex changing or genetic dimorphism, and 2) test predictions about a) the relationship between size and gender, and b) the association of size change and sex change. Twenty five to 37% of the flowering individuals in each population changed gender from one year to the next. Of the plants I followed for four years, 83% changed sex and 57% changed more than once. In each of these populations as well as two others, hermaphrodites were significantly larger than males. Gender dynamics of the three populations differed, but hermaphrodites tended to become smaller and were more likely to change gender than remain hermaphroditic the following year, whereas males tended to grow larger and were more likely to remain male than to change gender. Dwarf ginseng is clearly a diphasic (sex changing) species in which sex expression is determined primarily by size. A difference between genders in the immediate resource costs of reproduction appears to be an important determinant of sex change and gender phase ratios in populations.


Hearts from mice lacking desmin have a myopathy with impaired active force generation and unaltered wall compliance.
Desmin intermediate filaments are key structures in the cytoskeleton of cardiac muscle. Since they are associated with Z-discs and intercalated discs, they may have a role in sarcomere alignment or force transmission. We have explored the mechanical function of the desmin filaments in the cardiac wall by comparing desmin-deficient (Des-/-) and wild-type (Des+/+) mice. The Langendorff technique was used to examine the contractility of the whole heart. Rate of force generation, Ca(2+)-sensitivity and force per cross-sectional area were measured in skinned ventricle muscle preparations. Des-/- mice have a cardiomyopathy with increased heart weight. Diastolic pressure was increased at all filling volumes in the Des-/- group. Since passive wall stress (i.e. force per area) was unchanged, the alteration in diastolic pressure is a consequence of the thicker ventricle wall. Developed pressure, rate of pressure increase and developed wall stress were significantly reduced, suggesting that active force generation of the contractile apparatus is reduced in Des-/-. Concentrations of actin and myosin in the ventricle were unaltered. Measurements in skinned muscle preparations showed a lower active force development with unaltered Ca(2+)-sensitivity and rate of tension development. It is suggested that the intermediate filaments have a role in active force generation of cardiac muscle, possibly by supporting sarcomere alignment or force transmission. The desmin filaments do not contribute the passive elasticity of the ventricle wall. Des-/- mice provide a model for genetic cardiomyopathy where the main factor contributing to altered cardiac performance is a decrease in active force generation, possibly in combination with a loss of functional contractile units.


Correspondence of optimal stimulation and beta power varies regionally in STN DBS for Parkinson disease.
Subthalamic nucleus deep brain stimulation (STN DBS) for Parkinson disease (PD) normalizes neuronal hypersynchrony in the beta frequency range (13-30 Hz). The spatial correspondence of maximal beta power to the site of optimal stimulation along the DBS lead trajectory has been debated. We determined the trajectory locations of the active contact, maximal beta power, and the dorsal border of the STN (DB-STN) in DBS patients. Beta power profiles were measured during intraoperative microelectrode recording (MER). Active contact locations were assigned during blinded, postoperative DBS programming. The DB-STN was identified both electrophysiologically during MER and anatomically on MRI. After grouping DBS trajectories into quadrants relative to the anatomic STN midpoint, we examined regional variations in the relative trajectory locations of the three entities. STN DBS significantly improved motor performance for all 13 DBS patients, with active contacts at the DB-STN. Along trajectories passing posterior-medial to the STN midpoint, maximal beta power co-localized with active contacts at the DB-STN (difference Δ = 0.4 ± 1.6 mm, p = 0.57). By contrast, in posterior-lateral trajectories, maximal beta arose within the STN, ventral to active contacts (Δ = 1.9 ± 1.3 mm, p = 0.002). For trajectories anterior to the STN midpoint, maximal beta power co-localized with the DB-STN, while active contacts were ventral to peak beta power (p = 0.05). Our findings indicate that co-localization of optimal stimulation and beta power varies by anatomical region in STN DBS for Parkinson disease.


Ryanodine receptors are involved in muscarinic antinociception in mice.
The role of ryanodine receptors (RyRs) in the induction of muscarinic antinociception was investigated in a condition of acute thermal pain by means of the mouse hot-plate test. I.c.v. administration of non-hyperalgesic doses of ryanodine (0.001-0.06 nmol per mouse i.c.v.), an antagonist of ryanodine receptors (RyRs), dose-dependently prevented the antinociception induced by both physostigmine (100-150 microgkg(-1) s.c.) and oxotremorine (40-70 microgkg(-1) s.c.). A shift to the right of the dose-response curve of both cholinomimetic compounds was observed. Pretreatment with non-analgesic doses of 4-chloro-m-cresol (4-Cmc; 0.003-0.3 nmol per mouse i.c.v.), an agonist of RyRs, reversed in a dose-dependent manner the antagonistic effect produced by ryanodine of muscarinic antinociception. The pharmacological treatments employed neither modified the animals' gross behavior nor produced any behavioral impairment of mice as revealed by the rota-rod and hole-board tests. These results indicate that a variation of intracellular calcium contents at the central nervous system level is involved in muscarinic antinociception. In particular, the stimulation of RyRs appears to play an important role in the increase of the pain threshold produced by physostigmine and oxotremorine in mice.


The DNA demethylating agent decitabine activates the TRAIL pathway and induces apoptosis in acute myeloid leukemia.
Although epigenetic drugs have been approved for use in selected malignancies, there is significant need for a better understanding of their mechanism of action. Here, we study the action of a clinically approved DNA-methyltransferase inhibitor - decitabine (DAC) - in acute myeloid leukemia (AML) cells. At low doses, DAC treatment induced apoptosis of NB4 Acute Promyelocytic Leukemia (APL) cells, which was associated with the activation of the extrinsic apoptotic pathway. Expression studies of the members of the Death Receptor family demonstrated that DAC induces the expression of TNF-related apoptosis-inducing ligand (TRAIL). Upregulation of TRAIL, upon DAC treatment, was associated with specific epigenetic modifications induced by DAC in the proximity of the TRAIL promoter, as demonstrated by DNA demethylation, increased DNaseI sensitivity and histone acetylation of a non-CpG island, CpG-rich region located 2kb upstream to the transcription start site. Luciferase assay experiments showed that this region behave as a DNA methylation sensitive transcriptional regulatory element. The CpG regulatory element was also found methylated in samples derived from APL patients. These findings have been confirmed in the non-APL, AML Kasumi cell line, suggesting that this regulatory mechanism may be extended to other AMLs. Our study suggests that DNA methylation is a regulatory mechanism relevant for silencing of the TRAIL apoptotic pathway in leukemic cells, and further elucidates the mechanism by which epigenetic drugs mediate their anti-leukemic effects.


Breeding and characterization of amino acid-analogue-resistant mutants of Arthrospira platensis.
To obtain amino acid-analogue-resistant mutants the wild strain A9 of Arthrospira platensis was mutated by ethylmethane sulfonate (EMS). Mutagenic effects of strain A9 by EMS were studied. The experimental results indicated that the survival rate curve of strain A9 took a typical "exponential shape" with lethal dosage of EMS being 1%. The survival of A9 strain was 13.2% when treated with 0.4% of EMS, and the resistant mutation rates to two amino acid analogues, ρ-fluorophenylalanine (FPA) and L-canavanine sulphate (CS), were greatly increased with the highest rates being at 4.9 × 10(-4) and 3.24 × 10(-4), respectively. By repeated screening, two stable mutants resistant to amino acid analogues, A9f resistant to FPA and A9c resistant to CS, were obtained. Resistances of the two mutants to corresponding amino acid-analogues were both significantly increased. Compared with their parent strain A9, A9f appeared larger than A9 performance in filament diameter, spiral diameter, spiral pitch, filament length and spiral number, and A9c showed much longer length and spiral pitch than those of the initial strain. Analysis results on amino acids compositions and contents showed that both two mutants accumulated quite higher concentration of amino acids in cells. The two mutants might be excellent high amino acids producing strain. By this means two useful mutants with stable genetic makers for further genetic study of A. platensis were obtained, which laid a good foundation for further study on the transformation of A. platensis.


A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy.
Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P = 0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P = 0.0002), sex (P = 0.0009), serum albumen levels (P = 0.0018), performance status (P = 0.0026) and lactic dehydrogenase values (P = 0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months; P = 0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.


Hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with HCC: prognostic features before resection, ablation, or TACE.
Patients with hepatocellular carcinoma (HCC) receiving different treatments might have specific prognostic factors that can be captured in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI). We aimed to identify the clinical findings and HBP features with prognostic value in patients with HCC. In this retrospective, single-institution study, we included patients with Barcelona Clinic Liver Cancer very early/early stage HCC who underwent GA-MRI before treatment. After performing propensity score matching, 183 patients received the following treatments: resection, radiofrequency ablation (RFA), and transarterial chemoembolization (TACE) (n = 61 for each). Cox regression models were used to identify clinical factors and HBP features associated with disease-free survival (DFS) and overall survival (OS). In the resection group, large tumor size was associated with poor DFS (hazard ratio [HR] 4.159 per centimeter; 95% confidence interval [CI], 1.669-10.365) and poor OS (HR 8.498 per centimeter; 95% CI, 1.072-67.338). In the RFA group, satellite nodules on HBP images were associated with poor DFS (HR 5.037; 95% CI, 1.061-23.903) and poor OS (HR 9.398; 95% CI, 1.480-59.668). Peritumoral hypointensity on HBP images was also associated with poor OS (HR 13.062; 95% CI, 1.627-104.840). In addition, serum albumin levels and the prothrombin time-international normalized ratio were associated with DFS and/or OS. Finally, in the TACE group, no variables were associated with DFS/OS. Different HBP features and clinical factors were associated with DFS/OS among patients with HCC receiving different treatments. • In patients who underwent resection for HCC, a large tumor size on HBP images was associated with poor disease-free survival and overall survival. • In the RFA group, satellite nodules and peritumoral hypointensity on HBP images, along with decreased serum albumin levels and PT-INR, were associated with poor disease-free survival and/or overall survival. • In the TACE group, no clinical or HBP imaging features were associated with disease-free survival or overall survival.


The "Spirit 8" successfully captured spiritual well-being in African palliative care: factor and Rasch analysis.
To describe the dimensionality of a measure of spiritual well-being (SWB) (the "Spirit 8") in palliative care (PC) patients in South Africa and Uganda, and to determine SWB in this population. A cross-sectional survey was conducted using the Missoula Vitas Quality of Life Index (MVQOLI). Translated questionnaires were administered to consecutively recruited patients. Factor analysis and Rasch analysis were used to examine the dimensionality of eight items from the Well-being and Transcendent subscales. The resulting measure (the "Spirit 8") was used to determine levels of SWB. Two hundred eighty-five patients recruited; mean age 40.1; 197 (69.1%) female; primary diagnosis HIV (80.7%), cancer (17.9%). Internal consistency of the eight-item scale was α=0.73; Well-being factor α=0.69, Transcendence factor α=0.68. Rasch analysis suggested unidimensionality. Mean SWB score was 26.01 (standard deviation 5.68). Spiritual distress was present in 21.4-57.9%. Attending the Ugandan service, HIV and younger age were associated with poorer SWB scores. The Spirit 8 is a brief, psychometrically robust, unidimensional measure of SWB for use in South African and Ugandan PC research. Further research testing the Spirit 8 and examining the SWB of PC patients in South Africa and Uganda is needed to improve spiritual care.


Roflumilast N-oxide, a PDE4 inhibitor, improves cilia motility and ciliated human bronchial epithelial cells compromised by cigarette smoke in vitro.
Mucociliary malfunction occurs in chronic obstructive pulmonary disease (COPD) and compromised functions of ciliated bronchial epithelial cells may contribute to this. Cigarette smoke, a major risk factor for COPD, impairs ciliary beat frequency (CBF). cAMP augments CBF. This in vitro study addressed, in differentiated, primary human bronchial epithelial cells, whether roflumilast N-oxide, a PDE4 inhibitor, (i) augments CBF; (ii) prevents the reduction in CBF induced by cigarette smoke extract (CSE); and (iii) protects against the loss of the ciliated phenotype following long-term CSE exposure. Air-liquid interface cultured human bronchial epithelial cells were incubated with roflumilast N-oxide and exposed to CSE. CBF was assessed by digital high speed video microscopy (DHSV). Ciliated cells were characterized by β-tubulin IV staining and analyses of Foxj1 and Dnai2 mRNA and protein (real-time quantitative PCR, Western blotting). Roflumilast N-oxide concentration-dependently triggered a rapid and persistent increase in CBF and reversed the decrease in CBF following CSE. Long-term incubation of bronchial epithelial cells with CSE resulted in a loss in ciliated cells associated with reduced expression of the ciliated cell markers Foxj1 and Dnai2. The PDE4 inhibitor prevented this loss in the ciliated cell phenotype and the compromised Foxj1 and Dnai2 expression. The enhanced release of IL-13 following CSE, a cytokine that diminishes the proportion of ciliated cells and in parallel, reduces Foxj1 and Dnai2, was reversed by roflumilast N-oxide. Roflumilast N-oxide protected differentiated human bronchial epithelial cells from reduced CBF and loss of ciliated cells following CSE.


Tailoring surface structure of polymer nanospheres in Pickering emulsion polymerization.
A series of surface-functionalized polystyrene (PS) nanospheres with similar particles size of about 100 nm and adjusted content of sulfonate groups on the surface are prepared by Pickering emulsion polymerization using titania nanoparticles modified with a mixture of two surfactants as stabilizers. TEM and FE-SEM images indicate that the titania nanoparticles are firmly adsorbed on the surface of polymer nanospheres because of the electric attraction between negative charged surfactant molecules and positive charged titania particles. XPS and electrophoresis measurements confirm that the surfactant with a double bond has been successfully grafted on the surface of PS nanospheres, and the surfactant without a double bond is removed with titania nanoparticles. Polymer nanospheres with appropriate concentration of sulfonate groups on the surface have good colloidal stability in the nonpolar solvent and may be suitable for bistable electrophoretic display application.


Draft genome sequence of the cellulolytic Clostridium thermocellum wild-type strain BC1 playing a role in cellulosic biomass degradation.
The bacterium Clostridium thermocellum BC1, a thermophilic, anaerobic bacterium of the family Clostridiaceae, was isolated from a compost treatment site in Germany. It is able to grow efficiently on cellulose and cellodextrins. The draft genome sequence of C. thermocellum BC1 has been established and provides the genetic basis for application of this microorganism in thermophilic degradation of cellulosic biomass.


Comparison of the motor discharge to the voluntary sphincters of continence in the rat.
The rat external anal sphincter (EAS) and external urethral sphincter (EUS) are voluntary muscles of continence that can display similar synchronous electromyographic (EMG) activity patterns. However, the two sphincters are quite different in structure and function. The EUS is a fast twitch muscle and contains fibers expressing type 2B myosin. In contrast, the EAS exhibits slower kinetics and lacks type 2B fibers. This striking contrast in kinetics and fiber type profiles may be shaped by differences in the basal motor drive that each sphincter receives. A double EMG approach was used to obtain spontaneously active single motor unit action potentials from the EUS and EAS simultaneously and compare their basal discharge frequencies in urethane anaesthetized rats. The basal firing rates of motor units of the EUS and EAS were not significantly different (3.9 ± 0.9 Hz vs. 3.1 ± 1.6 Hz, respectively, n = 7 animals, P = 0.32, paired Student's t-test). However, auto-correlogram analysis showed that EUS is driven by neurons with faster instantaneous firing frequencies: 30.5 ± 2.4 Hz vs 14.3 ± 0.9 Hz in the EAS (P = 0.03, paired Student's t-test). The oscillator(s) driving the EUS operate(s) at a frequency twice that of the EAS. This may explain the presence of type 2B fibers in the EUS. In the inter-micturition periods no cross correlation was found in motor discharge to the sphincters suggesting that the two muscles do not share a common central drive to sustain the continent tonus of the two outlet tracts.


Occurrence and characterization of Listeria spp. in ready-to-eat retail foods from Vancouver, British Columbia.
The occurrence of Listeria spp. and Listeria monocytogenes in retail RTE meat and fish products in Vancouver, British Columbia (B.C.) was investigated. To assess potential consumer health risk, recovered L. monocytogenes isolates were subjected to genotypic and phenotypic characterization. Conventional methods were used to recover Listeria spp. from deli meat (n = 40) and fish (n = 40) samples collected from 17 stores. Listeria spp. were recovered only from fish samples (20%); 5% harboured Listeria innocua, 5% had L. monocytogenes and 10% contained Listeria welshimeri. L. monocytogenes isolates serotyped as 1/2a and 1/2b, possessed dissimilar PFGE patterns, and had full-length InlA. Three 1/2a clonal isolates encoded the 50 kb genomic island, LGI1. Antimicrobial resistance (AMR) profiling showed all Listeria spp. possessed resistance to cefoxitin and nalidixic acid. L. monocytogenes were resistant to clindamycin, two were resistant to streptomycin, and one to amikacin. Reduced susceptibility to ciprofloxacin was seen in all L. monocytogenes, L. innocua and three L. welshimeri isolates. Reduced susceptibility to amikacin and chloramphenicol was also observed in one L. monocytogenes and three L. welshimeri isolates, respectively. Recovery of L. monocytogenes in fish samples possessing AMR, full-length InlA, LGI1, and serotypes frequently associated with listeriosis suggest B.C. consumers are exposed to high-risk strains.


[Dependence of the duration of one mitotic cycle during synchronous cleavage divisions (tau o) on the temperature in 4 Rana species and the limits of the optimal temperatures for their reproduction and early development].
The dependence of the duration of one mitotic cycle during synchronous cleavage divisions (tau o) on temperature was studied in Rana temporaria, R. arvalis, R. lessonae, R. ridibunda and the corresponding curves were plotted in both linear and semilogarithmic scale. The curves can be used to characterize the relative duration of development, as well as to estimate the limits of optimal temperatures and to reveal the temperature-temporal regularities of development in these species.


Retraction.
Retraction: "AIB1 induces epithelial-mesenchymal transition in gastric cancer via the PI3K/AKT signaling," by Lei Diao, Yang Li, Qiao Mei, Wei Han, and Jing Hu, J Cell Biochem. 2021; 926-933: The above article, published online on November 6, 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/10.1002/jcb.29530) has been retracted by agreement between the authors, the journal's Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed after the authors stated that unintentional errors occurred during the research process, and the experimental results cannot be verified. Thus, the conclusions are considered to be invalid.


Ethical guidelines to publication of chemical research. American Chemical Society.
The guidelines embodied in this document were revised by the editors of the Publication Division of the American Chemical Society in January 1994 and endorsed by the Society Committee on Publications.


The quorum-sensing inhibiting effects of stilbenoids and their potential structure-activity relationship.
Stilbenoids, known an important phytoalexins in plants, were renowned for their beneficial effects on cardiovascular, neurological and hepatic systems. In the present study, quorum sensing inhibition activity of ten stilbenoids were tested using Chromobacterium violaceum CV026 as the bio-indicator strain and the structure-activity relationship was also investigated. Among them, resveratrol (1), piceatannol (2) and oxyresveratrol (3) showed potential anti-QS activities. At the sub-MIC concentrations, 1-3 demonstrated a statistically significant reduction of violacein in C. violaceum CV026 in a concentration dependent manner. Furthermore, the effects of 1-3 on QS regulated virulence factors in Pseudomonas aeruginosa PAO1 were also evaluated. Our results showed that the stilbenoids 1-3 can markedly decreased the production of pyocyanin and swarming motility of P. aeruginosa PAO1. Further transcriptome analyses showed that 1-3 suppressed the expression of QS-induced genes: lasR, lasI, rhlR and rhlI.


Ethnic Variations in Cardiovascular and Renal Outcomes From Newer Glucose-Lowering Drugs: A Meta-Analysis of Randomized Outcome Trials.
Background Hispanic populations are more likely to develop diabetes and its related diseases than non-Hispanic White populations. Little evidence exists to support whether the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists are generalizable to the Hispanic populations. Methods and Results We included the cardiovascular and renal outcome trials (up to March 2021) that reported the major adverse cardiovascular events (MACEs), cardiovascular death/hospitalization for heart failure, and composite renal outcomes by ethnicity in individuals with type 2 diabetes (T2D), calculated pooled hazard ratios (HRs) with 95% CIs using fixed-effects models, and tested the differences between Hispanic and non-Hispanic populations (P for interaction [Pinteraction]). In 3 sodium-glucose cotransporter 2 inhibitor trials, there was a statistically significant difference between Hispanic (HR, 0.70 [95% CI, 0.54-0.91]) and non-Hispanic (HR, 0.96 [95% CI, 0.86-1.07]) groups in treatment effects on MACE risk (Pinteraction=0.03), except for risks of cardiovascular death/hospitalization for heart failure (Pinteraction=0.46) and composite renal outcome (Pinteraction=0.31). In 5 glucagon-like peptide-1 receptor agonist trials, there was no statistically significant difference in treatment effect on MACE risk between Hispanic (HR, 0.82 [95% CI, 0.70-0.96]) and non-Hispanic (HR, 0.92 [95% CI, 0.84-1.00]) populations (Pinteraction=0.22). In 3 dipeptidyl peptidase-4 inhibitor trials, the HR for MACE risk appeared greater in Hispanic (HR, 1.15 [95% CI, 0.98-1.35]) than non-Hispanic (HR, 0.96 [95% CI, 0.88-1.04]) populations (Pinteraction=0.045). Conclusions Compared with non-Hispanic individuals, Hispanic individuals with T2D appeared to obtain a greater benefit of lowered MACE risk with sodium-glucose cotransporter 2 inhibitors.


Protecting or promoting effects of spermine on DNA strand breakage induced by iron or copper ions as a function of metal concentration.
Polyamines are ubiquitous polycations that participate in cellular processes such as growth, differentiation and cell death. Among the different functions ascribed to these organic cations, the polyamine spermine is known to protect DNA from the damage produced by reactive oxygen species (ROS) generated by different agents including copper ions. We have found that spermine exerts opposite effects on DNA strand breakage induced by Fenton reaction depending on metal concentration. Whereas at low concentration of the transition metals, 10 microM copper or 50 microM Fe(II), 1 mM spermine exerted a protective role, at metal concentrations higher than 25 microM copper or 100 microM Fe(II), spermine stimulated DNA strand breakage. The promotion of the damage induced by spermine was independent of DNA sequence but decreased by increasing the ionic concentration of the media or by the presence of metal-chelating agents. Moreover, spermine did not increase the oxidation of 2-deoxyribose by metal/H2O2 when DNA was substituted by 2-deoxyribose as a target for damage. Our results corroborate that spermine may protect DNA and 2-deoxyribose from the damage induced by ROS but also demonstrate that under certain conditions spermine may promote DNA strand breakage. The fact that this promoting effect of spermine on ROS-induced damage was observed only in the presence of DNA suggests that this polyamine under certain conditions may facilitate the interaction of copper and iron ions with DNA leading to the formation of ROS in close proximity to DNA.


Scaffolding student learning in clinical practice.
For many years the profession has acknowledged a schism between theories taught in the classroom and the practice of clinicians. This tends to arise from beliefs that knowledge which has been generalized (formalized) can be readily transferred to informal settings (practice). Whilst apprehension of formalized knowledge is crucial to professional development, a mediator is necessary to demonstrate its relevance to practice. A variety of solutions have been offered which all have value but without effective social support fail to resolve the problem. Findings from a longitudinal study investigating the professional development of pre-registration nursing students indicate the importance of sponsorship by a member of clinical staff and participation in legitimate peripheral activities. In the absence of effective sponsorship, students found it difficult to participate in clinical activities or to learn. As a result, their professional development during placements became stunted with subsequent implications for their professional future. Questions concerned with this phenomena were explored using documentary evidence supplied by research participants, observations of their practice and focused interviews throughout their programme. Sociocultural or activity theories of human learning offer some attractive explanations. One strategy is scaffolding which takes place within sponsored nursing activities and builds on the important concept of the Zone of Proximal Development (ZPD), where speech becomes a tool to mediate learning and development. As a diagnostic tool, scaffolding enables both supervisor and learner to recognize knowledge-in-waiting and knowledge-in-use and hence learning need, thus stimulating opportunities for further learning and professional development beneficial to both learner and supervisor. It provides a means for theory and practice to become integrated.


The Development and Validation of a Questionnaire to Investigate the Association Between Maternal Food Insecurity and Fetal Structural Anomalies: Delphi Procedure and Pilot Study.
Food insecurity represents a public health issue that has been associated with poor birth outcomes. We describe the methodological steps followed to structure and validate a questionnaire, which has the potential to contribute to the planning and conduction of future studies investigating the possible association between maternal food insecurity and fetal structural anomalies. We first conducted a literature review to structure and validate the questionnaire. Subsequently, we drafted the questionnaire based on the results of this review, further refined through two focus groups. Afterward, the questionnaire was submitted using the Delphi Method to a panel of experts for validation. We conducted a pilot study prior to recruiting the final sample. The questionnaire consisted of sections covering information about socio-demographic characteristics, women's health and lifestyle, pregnancy, and food security status. After the first Delphi round, the Content Validity Index (CVI) for each section ranged 0.81-0.85, while after the second round all items had a CVI of 1. The final version of the questionnaire, consisting of 87 items, was pilot tested among 20 participants. Cronbach's Alpha for each section resulted in values higher than 0.6. The response rate ranged from 78 to 100%. A situation of food security was present in 85% of the participants, while 5% were in a situation of mild food insecurity and 10% of moderate food insecurity. The questionnaire has appropriate measurement properties, and is an adequate instrument to evaluate the association between maternal food insecurity and fetal structural anomalies.


Sustained co-delivery of 5-fluorouracil and cis-platinum via biodegradable thermo-sensitive hydrogel for intraoperative synergistic combination chemotherapy of gastric cancer.
Gastric cancer is the fifth most common cancer and the third leading cause of cancer death worldwide, posing a severe threat to human health. Surgical resection remains the most preferred option for gastric cancer treatment. However, for advanced gastric cancer, the curative effect of surgical resection is usually limited by the local recurrence, peritoneal carcinomatosis, or distal metastasis. Intraoperative chemotherapy is an attractive in situ adjuvant treatment strategy to reduce the recurrence and metastasis after surgical resection. Here, we designed a 5-fluorouracil (5-FU) and cis-platinum (DDP) co-delivery system based on a biodegradable temperature-sensitive hydrogel (PDLLA-PEG-PDLLA, PLEL) for intraoperative adjuvant combination chemotherapy of gastric cancer. This 5-FU + DDP/PLEL hydrogel system characterized by a special sol-gel phase transition in response to physiological temperature and presented sustained drug release in vitro and in vivo. A strong synergistic cell proliferation inhibition and apoptosis promotion of 5-FU + DDP/PLEL were observed against gastric cancer MKN45-luc cells. After intraperitoneal injection, the dual-drug loaded hydrogel formulation showed superior anti-tumor effects than the single-drug carrying hydrogels and combination of free 5-FU and DDP on the gastric cancer peritoneal carcinomatosis model. The use of hydrogel for dual-drug delivery had benefited to fewer side effects as well. What's more, we established a mouse model for postsurgical residual tumors and peritoneal carcinomatosis of gastric cancer, in which the intraoperative administration of 5-FU + DDP/PLEL also remarkably inhibited the local recurrence of the orthotopic tumors and the growth of the abdominal metastatic tumors, resulting in an extended lifetime. Hence, this developed dual-drug loaded hydrogel system has great potential in the intraoperative chemotherapy of gastric cancer, that suggests a clinically-relevant and valuable option for postsurgical management of gastric cancer.


Thickness of the gerbil tympanic membrane measured with confocal microscopy.
Thickness data for the gerbil tympanic membrane, an extremely thin biological membrane, are presented. Thickness measurements were performed on fresh material using fluorescence images taken perpendicular through the membrane with a commercial confocal microscope. Thickness varies strongly across the membrane. Similar thickness distributions in all samples (pars tensa n = 11; pars flaccida n = 3) were observed. The pars tensa has a rather constant thickness of about 7 microm in the central region curving as a horse shoe upwards around the manubrium. In the most superior parts of the pars tensa thickness becomes gradually twice as large. Thickness increases also steeply from the central region towards the edges (about 35 microm near the annulus and 20 microm near the manubrium). A pronounced, local thickening of about 30 microm is present close to the edge and extends as a ring along the entire annular periphery of the pars tensa. Overall, the pars flaccida is thicker than the pars tensa and has a rugged surface. Its central region has a mean thickness of about 24 microm with a mean variation of about 4 microm. The average thickness in the inferior region is slightly larger than in the superior region. The pars flaccida thickens steeply, up to about 80 microm, near the edges.


Decrease of intragastric acidity in healthy subjects dosed with ranitidine 75 mg, cimetidine 200 mg, or placebo.
This study assessed the duration of action of single doses of ranitidine (75 mg), cimetidine (200 mg), or placebo on intragastric acidity in healthy subjects. When dosed with placebo, mean daytime intragastric acidity (0-10 hr after dose) was 37.62 mmol/liter, decreasing to 17.21 mmol/liter (mean decrease 59%; P < 0.001 vs placebo) and 25.06 mmol/liter (mean decrease 35%; P < 0.001 vs placebo) when treated with ranitidine and cimetidine, respectively. Ranitidine inhibited intragastric acidity to a greater degree than cimetidine (P < 0.001). Mean nighttime (10-20 hr after-dose) intragastric acidity when dosed with placebo was 34.37 mmol/liter, decreasing to 29.06 mmol/liter (mean decrease 18%; P = 0.027 vs placebo) when dosed with ranitidine and remaining virtually unchanged at 33.85 mmol/liter (mean decrease 2%; NS vs. placebo) when dosed with cimetidine. Ranitidine inhibited acidity to a greater degree than cimetidine (P = 0.043). The inhibitory effect of ranitidine, 75 mg, on intragastric acidity can be detected from 0-15 hr after an oral dose. Cimetidine 200 mg has little inhibitory effect beyond 10 hr.


Pseudogenization of the chloroplast threonine (trnT-GGU) gene in the sunflower family (Asteraceae).
The chloroplast genome evolves through the course of evolution. Various types of mutational events are found within the chloroplast genome, including insertions-deletions (InDels), substitutions, inversions, gene rearrangement, and pseudogenization of genes. The pseudogenization of the chloroplast threonine (trnT-GGU) gene was previously reported in Cryptomeria japonica (Cupressaceae), Pelargonium × hortorum (Geraniaceae), and Anaphalis sinica and Leontopodium leiolepis of the tribe Gnaphalieae (Asteroideae, Asteraceae). Here, we performed a broad analysis of the trnT-GGU gene among the species of 13 subfamilies of Asteraceae and found this gene as a pseudogene in core Asteraceae (Gymnarrhenoideae, Cichorioideae, Corymbioideae, and Asteroideae), which was linked to an insertion event within the 5' acceptor stem and is not associated with ecological factors such as habit, habitat, and geographical distribution of the species. The pseudogenization of trnT-GGU was not predicted in codon usage, indicating that the superwobbling phenomenon occurs in core Asteraceae in which a single transfer RNA (trnT-UGU) decodes all four codons of threonine. To the best of our knowledge, this is the first evidence of a complete clade of a plant species using the superwobbling phenomenon for translation.


Antibodies to diethylcarbamazine cross-react with microfilariae of Wuchereria bancrofti.
Antibodies directed against the microfilarial sheath have been instrumental in the immune elimination of circulating microfilariae in human lymphatic filariasis. We report here that antibodies to diethylcarbamazine (DEC, the most commonly used anti-filarial drug) cross-react with the sheath of Wuchereria bancrofti microfilariae. Antibodies with reactivity to DEC were raised in rabbits by immunization with a conjugate of methylpiperazine carboxylic acid (MPCA, an acid hydrolysis product of DEC) coupled to bovine serum albumin. The reactivity of these antibodies with microfilarial sheath of W. bancrofti was demonstrated by indirect immunofluorescent assay and indirect immunoperoxidase assay. This reactivity could be effectively inhibited by pre-incubation of the antisera with different haptens such as DEC, MPCA or piperazine citrate.


Intestinal villus and crypt cell responses to cholera toxin.
Adenylate cyclase activity was measured in rat small intestinal villus and crypt cells after in vivo and in vitro exposure to cholera toxin. The increase in intestinal adenylate cyclase induced by cholera toxin in vivo appeared to be largely confined to the villus cell with the largest increase observed for upper villus cells. Crypt cell adenylate cyclase was not responsive to cholera toxin. No response could be demonstrated for isolated villus or crypt cells incubated with cholera toxin in vitro. In vivo incubation with 125I-cholera toxin demonstrated binding to only villus cells. These results suggest that the major effect of cholera toxin was on villus cells rather than crypt cells and this was due to the greater accessibility or binding capacity of the villus cell to luminal cholera toxin.


Single-atom nanozymes: From bench to bedside.
Single-atom nanozymes (SANs) are the new emerging catalytic nanomaterials with enzyme-mimetic activities, which have many extraordinary merits, such as low-cost preparation, maximum atom utilization, ideal catalytic activity, and optimized selectivity. With these advantages, SANs have received extensive research attention in the fields of chemistry, energy conversion, and environmental purification. Recently, a growing number of studies have shown the great promise of SANs in biological applications. In this article, we present the most recent developments of SANs in anti-infective treatment, cancer diagnosis and therapy, biosensing, and antioxidative therapy. This text is expected to better guide the readers to understand the current state and future clinical possibilities of SANs in medical applications.


Serum carcinoembryonic antigen (CEA) as a clinical marker in acquired idiopathic generalized anhidrosis: a close correlation between serum CEA level and disease activity.
Hypohidrosis/anhidrosis are congenital or acquired sweating impairments. Among them, acquired idiopathic generalized anhidrosis/hypohidrosis (AIGA) is the most common, and characterized by favourable response to systemic corticosteroid, however, no clinical markers for disease severity or activity have been developed. Our aim was to verify the usefulness of serum carcinoembryonic antigen (CEA) level monitoring as a clinical marker for disease activity of AIGA. Ten cases of AIGA diagnosed at Asahikawa Medical University, from 1980 to 2014 were included in the study. CEA and/or CEACAM1 expression level was analysed using immunohistochemistry and enzyme-linked immunosorbent assay. CEA expression was restricted to the apical membrane of glandular cells in eccrine sweat glands in most of the three types of cases we examined [healthy control, patients with atopic dermatitis (AD) or urticaria]. However, CEA expression was detected diffusely and much more intensively in eight of the 10 AIGA cases included in this study. CEACAM1-expression was much more restricted on the apical membrane of glandular cells of both the AIGA cases and the other control subjects. While serum CEA levels increased in all five AIGA cases examined (5.8-43.2 ng/mL), it remained within normal limits in all control subjects: nine healthy individuals; 10 cases of AD; 10 cases of idiopathic urticaria; four cases of normohidrotic cholinergic urticaria (Mann-Whitney's U-test, P < 0.05). The increased serum CEA levels in AIGA decreased in conjunction with improved sweating during methyl prednisolone pulse therapy or repeated bathing. Serum CEA level may serve as a clinical marker for AIGA activity.


[Age dependence of some hematological parameters in the Wistar:Schönwalde strain of white laboratory rat].
We investigated the haematological response to growth of male and female rats of an outbred stock of Wistar rats (Wistar:Sch onwalde ) from the 4th to the 18th week of age. There exists in some parameters a difference between both sexes. Most values of red blood picture are in close correlation to body weight. Our values differ from those in literature, especially in red blood picture. The possible causes are discussed.


Removal of mucus for ultrastructural observation of the surface of human gastric epithelium using pronase.
Helicobacter pylori adhering to the human gastric epithelium causes gastric diseases such as ulcer, carcinoma and lymphoma. It is thus important to observe in detail both the surface of the epithelial cells and the H. pylori that adhered to it for the elucidation of H. pylori-induced diseases by scanning electron microscopy (SEM). Since the thick mucus layer blocks the observation of the cell surface and the bacteria, it is generally eliminated during the processing for SEM by roughly mechanical methods, but these treatments also demolish the ultrastructure of the cells. We studied the nonmechanical method for removal of mucus layer of gastric epithelium using pronase. To determine the optimal concentration of pronase, mucin was used as a substrate for inhibition of the viscosity. Pronase was added in 2% mucin at the concentration of 10, 50, 100, 500, 1000, 2000 or 5000 unit/ml and the flowing time of the mixture was measured. Based on the digestion experiment, biopsied specimens from 24 patients with dyspepsic symptoms were fixed in glutaraldehyde and then washed in rolling with different concentration of pronase. After the pretreatment by pronase, the specimens were treated according to the standard process for SEM. We succeeded in removing the mucus layer on the surface of epithelial cells from the biopsied specimens fixed in glutaraldehyde by rinsing with 2000 unit/ml pronase for 24 hours. Using our digestive method without destroying the ultrastructure, the earliest stage which H. pylori has adhered onto the human gastric epithelium can be observed for the investigation of H. pylori-induced gastric disorders by SEM.


Dosing information for paediatric patients: are they really "therapeutic orphans"?
To review the approved product information (PI) of prescription medicines to determine the extent and nature of information available on paediatric dosing and the availability of paediatric dosage formulations in Australia. The PIs for all prescription medicines listed in the Australian Monthly Index of Medical Specialties (MIMS) were reviewed. Dosing information for each PI was categorised according to age groupings. PIs claiming suitability for use in paediatric patients were reviewed for information on the availability of paediatric dosage forms. Proportion of PIs providing paediatric dosing information; availability of dosage forms suitable for children. A total of 1497 PIs were reviewed. The proportions, for each age group, of PIs with inadequate paediatric dosing information were: < 1 month (80.5%), 1-3 months (79.1%), 3 months-2 years (77.5%), 2-6 years (73.2%), and 6-12 years (71.6%). The proportions, for each age group, of PIs that gave specific paediatric dosing information but did not provide a paediatric dosage form were: < 1 month (26.5%), 1-3 months (25.1%), 3 months-2 years (23.3%), 2-6 years (21.9%), and 6-12 years (24.0%). The PIs for many prescription products listed in MIMS do not adequately detail paediatric doses. Many medicines for which specific paediatric dosing information is given are not available in dosage forms appropriate for children.


Outbreaks of hydropericardium syndrome and molecular characterization of Korean fowl adenoviral isolates.
Outbreaks ofhydropericardium syndrome (HPS), caused by fowl adenovirus serotype 4 (FAdV-4), have occurred in Korea and caused severe economic loss due to mortality and weight loss. From these outbreaks, several adenoviruses were isolated and identified in samples from broilers, layers, breeders, and native Korean fowl. In pathologic examinations, hydropericardium and multifocal hepatic necrosis, with an intranuclear inclusion body in hepatocytes, were observed. Specific adenovirus particles were also observed in the nucleus of hepatocytes, by electron microscopic examination. Polymerase chain reaction (PCR) analysis of the hexon gene identified all of the isolates as FAdV, serotype 4 and genotype C. To reproduce FAdV-4 field cases, 8- and 52-week-old specific pathogen free (SPF) chicks were infected intramuscularly with the field isolate CBU070244. The mortality rate of infected chicks ranged from 10%-40%, and specific pathologic lesions, such as swollen livers and hydropericardium, were observed. Further studies to determine the prevalence of infection, and analysis of the economic impact to the poultry industry, are needed in the near future.


Association between serum lactate dehydrogenase and 60-day mortality in Chinese Hakka patients with acute myeloid leukemia: A cohort study.
There is evidence that a high level of serum lactate dehydrogenase (LDH) is associated with poorer overall survival in acute myeloid leukemia (AML), but its link to 60-day mortality of AML remains unclear. All patients newly diagnosed with AML were included in this cohort study. LDH was measured for the first time after admission. Multivariable logistic regression was used to explore the association between serum LDH and 60-day mortality. Interaction and stratified analyses were conducted including age, sex, albumin, glucose, myoglobin, and standard chemotherapy. Three hundred and seventy-one patients ≥15 years of age, who were newly diagnosed with AML, were consecutively selected. The total prevalence of 60-day mortality was 27.2% (101/371), while it was 32.1% (42/131) and higher than in the LDH ≥570U/L compared with the LDH<570U/L, with the prevalence of 24.6% (59/240); however, the difference was not statistically significant. In multivariate regression models, odd ratios and corresponding 95% confidence intervals (CIs) for Log2 and twice limit of normal (ULN) of LDH were 1.46 (1.0, 2.14) and 2.76 (1.24, 6.16), respectively. Interaction analysis revealed no interactive role in the association between LDH concentration and 60-day mortality. Serum LDH level was associated with 60-day mortality, especially for the patients with LDH ≥570U/L.


Bioeconomy as a transforming driver of intensive greenhouse horticulture in SE Spain.
Bioeconomy is becoming the main driver transforming European agri-food value chains towards global sustainability in the food supply chain. Intensive horticultural production systems based on medium and low-tech greenhouses are suitable scenarios implementing bioeconomy strategies to achieve sustainability targets. Since the publication of the European Strategy of Bioeconomy in 2012, policy measures intended to boost bioeconomy are responsible for changing what are now considered outdated production systems to more high-tech models capable of responding to climate-change challenges. This article describes the potential for the agri-food supply chain to drive the transition of medium and low-tech intensive greenhouse systems to biobased, circular economy value-chains. Key areas of impact relate to waste valorisation and management, new inputs based on biotechnological innovations, building clusters of innovative delivery partners within the sector, and the increase in public awareness of the impact of the bioeconomy through socio-economic analysis.


Validity threats: overcoming interference with proposed interpretations of assessment data.
Factors that interfere with the ability to interpret assessment scores or ratings in the proposed manner threaten validity. To be interpreted in a meaningful manner, all assessments in medical education require sound, scientific evidence of validity. The purpose of this essay is to discuss 2 major threats to validity: construct under-representation (CU) and construct-irrelevant variance (CIV). Examples of each type of threat for written, performance and clinical performance examinations are provided. The CU threat to validity refers to undersampling the content domain. Using too few items, cases or clinical performance observations to adequately generalise to the domain represents CU. Variables that systematically (rather than randomly) interfere with the ability to meaningfully interpret scores or ratings represent CIV. Issues such as flawed test items written at inappropriate reading levels or statistically biased questions represent CIV in written tests. For performance examinations, such as standardised patient examinations, flawed cases or cases that are too difficult for student ability contribute CIV to the assessment. For clinical performance data, systematic rater error, such as halo or central tendency error, represents CIV. The term face validity is rejected as representative of any type of legitimate validity evidence, although the fact that the appearance of the assessment may be an important characteristic other than validity is acknowledged. There are multiple threats to validity in all types of assessment in medical education. Methods to eliminate or control validity threats are suggested.


Frequency and Clinical Associating Factors of Valvular Heart Disease in Asymptomatic Korean Adults.
Limited information is available on the prevalence and clinical determinants of valvular heart disease (VHD) in apparently healthy people. This study sought to assess the frequency and clinical associating factors of aortic stenosis (AS), aortic regurgitation (AR), mitral stenosis (MS), mitral regurgitation (MR), tricuspid regurgitation (TR) in asymptomatic individuals with health check-up examination. We included 23,254 subjects ≥50 years of age who underwent a health check-up examination with transthoracic echocardiography (TTE) between 2012 and 2016 in a single tertiary-care hospital in Korea. Among a total of 23,254 subjects, 15,358 men (66.0%) and 7,896 women (34.0%) underwent TTE. Newly identified (predominantly mild) VHD was detected in 9.4% of subjects. The most common VHD were TR (4.6%), AR (3.0%) and MR (2.4%). Clinically significant (more than moderate) VHD was identified in 176 subjects (0.8%). Age ≥75 years was associated with all clinically significant VHD, and female gender was associated with AR, MS and TR. Korea has been very active in the health check-up examination including echocardiography. We find that VHD in apparently healthy people is not uncommon than believed; all VHD except MS were more frequent in elderly over 75 years of age in a large population-based study.


Idiopathic generalized epilepsies: Which seizure type is more difficult to control?
The purpose of the current study was to investigate that which seizure type is more difficult to be brought under control with antiseizure medication treatment in patients with idiopathic generalized epilepsy (IGE). This was a retrospective study of a large database of patients with epilepsy, which was built over more than a decade. All patients with a diagnosis of IGE, with at least 12 months of follow-up at our center, were studied at the epilepsy center at Shiraz University of Medical Sciences, Shiraz, Iran, from 2008 until 2022. 358 patients were included. The seizure types were generalized tonic-clonic seizures (GTCSs) (in 87.2%), myoclonic seizures (in 57.5%), and absence seizures (in 51.7%). Among patients who had GTCSs (N = 312), 160 patients (51.3%) became free of this seizure type. Among patients who had myoclonic seizures (N = 206), 122 patients (59.2%) became seizure-free. Among patients who had absences (N = 185), 127 patients (68.6%) became seizure-free. The difference between the groups was significant (p = 0.0007). Receiving valproate was significantly associated with a myoclonus-free status (compared with other drugs). The likelihood of achieving seizure control is different for various seizure types in patients with IGE (achievement of seizure control is less likely for GTCSs and more likely for absences). Antiseizure drug efficacy should be considered along with other variables (e.g., sex) when selecting an ASM for a patient with IGE. Specifically designed clinical trials are needed to develop more efficacious and safe drugs to treat various syndromes of IGE.


Positioning accuracy during VMAT of gynecologic malignancies and the resulting dosimetric impact by a 6-degree-of-freedom couch in combination with daily kilovoltage cone beam computed tomography.
To improve the delivery of radiotherapy in gynecologic malignancies and to minimize the irradiation of unaffected tissues by using daily kilovoltage cone beam computed tomography (kV-CBCT) to reduce setup errors. Thirteen patients with gynecologic cancers were treated with postoperative volumetric-modulated arc therapy (VMAT). All patients had a planning CT scan and daily CBCT during treatment. Automatic bone anatomy matching was used to determine initial inter-fraction positioning error. Positional correction on a six-degrees-of-freedom (6DoF) couch was followed by a second scan to calculate the residual inter-fraction error, and a post-treatment scan assessed intra-fraction motion. The margins of the planning target volume (MPTV) were calculated from these setup variations and the effect of margin size on normal tissue sparing was evaluated. In total, 573 CBCT scans were acquired. Mean absolute pre-/post-correction errors were obtained in all six planes. With 6DoF couch correction, the MPTV accounting for intra-fraction errors was reduced by 3.8-5.6 mm. This permitted a reduction in the maximum dose to the small intestine, bladder and femoral head (P=0.001, 0.035 and 0.032, respectively), the average dose to the rectum, small intestine, bladder and pelvic marrow (P=0.003, 0.000, 0.001 and 0.000, respectively) and markedly reduced irradiated normal tissue volumes. A 6DoF couch in combination with daily kV-CBCT can considerably improve positioning accuracy during VMAT treatment in gynecologic malignancies, reducing the MPTV. The reduced margin size permits improved normal tissue sparing and a smaller total irradiated volume.


Alpha-ribazole, a fluorescent marker for the liquid chromatographic determination of vitamin B12 in foodstuffs.
A method to determine the contents of free vitamin B12 in various foods by reversed phase liquid chromatography-fluorimetry is reported. It includes a purification of the samples by passage through an immunoaffinity column and a pre-column conversion of vitamin B12 into the fluorescent alpha-ribazole (successive treatments of the extract with 2.5 M sodium hydroxide (at 100 degrees C for 15 min) and alkaline phosphatase (7.5 U) at 37 degrees C and pH 8 for 16 h). An enzymatic hydrolysis prior to the purification step (pepsin at 37 degrees C and pH 4 for 3 h) made it possible to release the vitamin B12 bound to proteins and thus to obtain the total vitamin B12 contents of these foodstuffs. The method proposed for the determination of free and bound vitamin B12 gives a good recovery rate (95-100%) and a satisfactory repeatability (R.S.D.r between 1.0 and 5.4%). Owing to its low quantification limit (3 ng g(-1)) and the good resolution of the alpha-ribazole peak, it could most probably be applied to the determination of this vitamin in any foodstuff.


Infrared spectroscopic characterization of monocytic microvesicles (microparticles) released upon lipopolysaccharide stimulation.
Microvesicles (MVs) are involved in cell-cell interactions, including disease pathogenesis. Nondestructive Fourier-transform infrared (FTIR) spectra from MVs were assessed as a technique to provide new biochemical insights into a LPS-induced monocyte model of septic shock. FTIR spectroscopy provided a quick method to investigate relative differences in biomolecular content of different MV populations that was complementary to traditional semiquantitative omics approaches, with which it is difficult to provide information on relative changes between classes (proteins, lipids, nucleic acids, carbohydrates) or protein conformations. Time-dependent changes were detected in biomolecular contents of MVs and in the monocytes from which they were released. Differences in phosphatidylcholine and phosphatidylserine contents were observed in MVs released under stimulation, and higher relative concentrations of RNA and α-helical structured proteins were present in stimulated MVs compared with MVs from resting cells. FTIR spectra of stimulated monocytes displayed changes that were consistent with those observed in the corresponding MVs they released. LPS-stimulated monocytes had reduced concentrations of nucleic acids, α-helical structured proteins, and phosphatidylcholine compared with resting monocytes but had an increase in total lipids. FTIR spectra of MV biomolecular content will be important in shedding new light on the mechanisms of MVs and the different roles they play in physiology and disease pathogenesis.-Lee, J., Wen, B., Carter, E. A., Combes, V., Grau, G. E. R., Lay, P. A. Infrared spectroscopic characterization of monocytic microvesicles (microparticles) released upon lipopolysaccharide stimulation.


Specialized pro-resolving lipid mediators: A new class of non-immunosuppressive and non-opioid analgesic drugs.
We now appreciate that the mechanism of resolution depends on an active and time-dependent biosynthetic shift from pro-inflammatory to pro-resolution mediators, the so-called specialized pro-resolving lipid mediators (SPMs). These SPMs are biosynthesized from the omega-3 fatty acids arachidonic acid (AA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), or docosahexaenoic acid (DHA). Despite effective for a fraction of patients with rheumatic diseases and neuropathic pain, current analgesic therapies such as biological agents, opioids, corticoids, and gabapentinoids cause unwanted side effects, such as immunosuppression, addiction, or induce analgesic tolerance. A growing body of evidence demonstrates that isolated SPMs show efficacy at very low doses and have been successively used as therapeutic drugs to treat pain and infection in experimental models showing no side effects. Moreover, SPMs work as immunoresolvents and some of them present long-lasting analgesic and anti-inflammatory effects (i.e. block pain without immunosuppressive effects). In this review, we focus on how SPMs block pain, infection and neuro-immune interactions and, therefore, emerge as a new class of non-immunosuppressive and non-opioid analgesic drugs.


Combined statistical analysis method assessing fast versus slow movement training in a patient with cerebellar stroke: a single-case study.
Gold standards of data analysis for single-case research do not currently exist. The purpose of this study was to determine whether a combined statistical analysis method is more effective in assessing movement training effects in a patient with cerebellar stroke. A crossover single-case research design was conducted. The patient was a 69-year-old man with a chronic cerebellar infarct who received two 5-week phases of finger tracking training at different movement rates. Changes were measured with the Box and Block Test, the Jebsen-Taylor test, the finger extension force test, and the corticospinal excitability test. Both visual analysis and statistical tests (including split-middle line method, t test, confidence interval, and effect size) were used to assess potential intervention effects. The results of the t tests were highly consistent with the confidence interval tests, but less consistent with the split-middle line method. Most results produced medium to large effect sizes. The possibility of an incomplete washout effect was a confounding factor in the current analyses. The combined statistical analysis method may assist researchers in assessing intervention effects in single-case stroke rehabilitation studies.


Association between parents' work hours and nutrient inadequacy in Japanese schoolchildren on weekdays and weekends.
Evidence is sparse concerning whether the nutrient intake in schoolchildren differs according to parents' work hours. The aim of this study was to investigate the relationship between parents' work hours and nutrient inadequacy among Japanese primary schoolchildren using dietary reference intakes on days with and without a school lunch. Participants included 10- to 11-y-old children in grade 5 from 19 public primary schools in four prefectures of east Japan. Data for 699 children were analyzed. Participants completed 24-h dietary records with photographs of their meals for 4 d consecutively, which included of 2 d of weekdays and 2 d of weekends. Their mothers' and fathers' work hours were obtained from questionnaires that were completed by the participants' guardians. Logistic regression analyses were used to estimate the odds ratios for whether participants had poor nutrient intake, with adjustment for confounders. Children whose mothers worked ≥40 h/wk had significantly higher rates of nutrient shortages for vitamins A, E, K, and B6, pantothenic acid, potassium, magnesium, and iron (P = 0.007, 0.003, 0.007, 0.023, 0.021, 0.045, 0.004, and 0.009, respectively) than those in the 0 h/wk group. These differences were not significant based on fathers' working hours, with the exception of vitamin A (≥40 versus 0-39 h/wk, P = 0.032). Additionally, nutrient shortages for children were more pronounced on weekdays than on weekends. This evidence revealed the necessity to improve nutrition intake in children whose mothers work more than statutory working hours, which would enable children to have adequate nutrient intake, especially on weekdays.


Prevalence of mental disorders in patients with cancer compared to matched controls - secondary analysis of two nationally representative surveys.
To compare prevalence rates of mental disorders in patients with cancer and general population controls. In two stratified nationally representative surveys, the 12-month prevalence of mental disorders was assessed in 2141 patients with cancer and 4883 general population controls by the standardized Composite International Diagnostic Interview (CIDI). We determined odds ratios (ORs) to compare the odds for mental disorders (combined and subtypes) in cancer patients with age- and gender-matched controls. The 12-month prevalences rate for any mental disorder was significantly higher in patients with cancer compared to controls (OR 1.28, 95% CI 1.14-1.45). Prevalence rates were at least two times higher for unipolar mood disorders (major depression: OR 2.07, 95% CI 1.71-2.51; dysthymia: OR 2.93, 95% CI 2.13-4.02) and mental disorders due to a general medical condition (OR 3.31, 95% CI 2.32-4.71). There was no significant elevation for anxiety disorders overall (OR 0.95, 95% CI 0.81-1.11). Mildly elevated prevalence rates emerged for post-traumatic stress disorder (OR 1.57, 95% CI 1.11-2.23) and social phobia (OR 1.57, 95% CI 1.07-2.31), while specific phobia (OR 0.82, 95% CI 0.67-1.00) and agoraphobia (OR 0.49, 95% CI 0.33-0.73) were significantly less frequent in cancer. While elevated depression rates reinforce the need for its systematic diagnosis and treatment, lower prevalences were unexpected given previous evidence. Whether realistic illness-related fears and worries contribute to lower occurrence of anxiety disorders with excessive fears in cancer may be of interest to future research.


Estrogenic and antiestrogenic regulation of MMP-2 and MMP-13 mRNA in RUCA-I endometrial tumor cells in vitro and in vivo.
We investigated the influence of estrogenic and antiestrogenic treatment on proteolytic activity--especially on MMP-2 and MMP-13--in the RUCA-I transplantable endometrial tumor model. Morphological studies demonstrate that RUCA-I cells are forming highly differentiated gland-like structures by remodelling and invading the underlying ECM. Estrogens upregulate the mRNA levels of MMP-2 and MMP-13 in the rat uterus. Treatment with the pure antiestrogen ICI 182,780 results in the downregulation of MMP-2 and MMP-13 mRNA. The same regulation for MMP-13 mRNA is found in vitro in RUCA-I cells. In contrast, in the transplantation tumor, the mRNA level of MMP-13 is repressed by estrogens and induced by ICI 182,780. MMP-2 mRNA is not regulated by hormones in the transplantation tumor and in RUCA-I cells. The divergent regulation suggests a varying influence of cell-cell-, cell-extracellular matrix interactions and soluble factors.


Adverse effects of second-generation antipsychotics in children and adolescents: a Bayesian meta-analysis.
In adults, second-generation antipsychotics (SGAs) have a low frequency of extrapyramidal syndrome (EPS) and a moderate frequency of metabolic adverse effects. Here we aimed to assess short-term adverse effects of SGAs in children and adolescents. We searched for relevant studies in MEDLINE and EMBASE (1996-2010), Food and Drug Administration and European Medicines Agency clinical trial registries, and reference lists of review articles. We found 41 were short-term (3-12 weeks) controlled studies that evaluated SGA adverse effects in youths. Using Bayesian meta-analysis, we analyzed odds ratios (ORs) or mean average effects. Numbers of arms (subjects) in the 41 trials were aripiprazole, 10 (n = 671); olanzapine, 14 (n = 413); quetiapine, 10 (n = 446); risperidone, 25 (n = 1040); ziprasidone, 4 (n = 228); clozapine, 5 (n = 79); and placebo/untreated, 23 (n = 1138), totaling 93 arms (4015 patients). Clozapine was assessed only for weight gain and somnolence. Compared with placebo, significant treatment-related increases were observed for weight gain with olanzapine (mean ± SD = 3.99 ± 0.42 kg; 95% credible interval, 3.17-4.84 kg), clozapine (2.38 ± 1.13 kg; 95% credible interval, 0.19-4.62 kg), risperidone (2.02 ± 0.32 kg; 95% credible interval, 1.39-2.66 kg), quetiapine (1.74 ± 0.38 kg; 95% credible interval, 0.99-2.5 kg), and aripiprazole (0.89 ± 0.32 kg; 95% credible interval, 0.26-1.51 kg); glucose levels with risperidone (3.7 ± 1.36 mg/dL; 95% credible interval, 1.08-6.42 mg/dL) and olanzapine (2.09 ± 1.08 mg/dL; 95% credible interval, 0.13-4.32 mg/dL); cholesterol levels with quetiapine (10.77 ± 2.14 mg/dL; 95% credible interval, 6.6-14.95 mg/dL) and olanzapine (4.46 ± 1.65 mg/dL; 95% credible interval, 1.24-7.73 mg/dL); triglyceride levels with olanzapine (20.18 ± 5.26 mg/dL; 95% credible interval, 9.85-30.53 mg/dL) and quetiapine (19.5 ± 3.92 mg/dL; 95% credible interval, 11.84-27.17 mg/dL); hyperprolactinemia with risperidone (OR, 38.63; 95% credible interval, 8.62-125.6), olanzapine (OR, 15.6; 95% credible interval, 4.39-41.1), and ziprasidone (OR, 9.35; 95% credible interval, 1.24-37.03); and EPS with ziprasidone (OR, 20.56; 95% credible interval, 3.53-68.94), olanzapine (OR, 6.36; 95% credible interval, 2.43-13.84), aripiprazole (OR, 3.79; 95% credible interval, 2.17-6.17), and risperidone (OR, 3.71; 95% credible interval, 2.18-6.02). All SGAs increased the risk of somnolence/sedation. We conclude that short-term metabolic effects and EPS are frequent in children treated with SGAs. Second-generation antipsychotics have distinct profiles of secondary effects, which should be considered in making treatment decisions.


Direct and indirect effects of predation on mosquitofish behavior and survival.
Predation can have strong direct and indirect effects on the behavior of prey. We investigated whether predation by chain pickerel (Esox niger) caused adult eastern mosquitofish (Gambusia holbrooki) to alter their habitat use and whether pickerel predation influenced survival of adult and neonate mosquitofish. The number of adult mosquitofish using the riskier of three habitats was lowest when two predators occupied the risky habitat, intermediate in the treatment with one predator, and highest when no predators occurred there. More mosquitofish neonates survived high predation treatments than treatments lacking pickerel. We conclude that pickerel predation causes adult mosquitofish to shift to refuge habitats. The pattern of neonate survival suggests that adult habitat use may create a refuge from cannibalism for neonate mosquitofish, resulting in higher neonate survival in treatments with more pickerel. Hence, pickerel predation has a direct effect on adult mosquitofish behavior and a strong indirect effect on neonate survival. Both interspecific and intraspecific predation can effect prey populations and can interact to produce important indirect effects.


Effect of an Education Presentation On the Knowledge and Awareness of Urinary Tract Infection among Non-Licensed and Licensed Health Care Workers in Long-Term Care Facilities.
This article presents the findings of a pre-test, post-test quality improvement project that describes the change in knowledge from prior to and following an evidence-based education presentation. The presentation addressed the clinical symptoms, diagnostic processes, interventions, and responsibilities of licensed and unlicensed health care workers employed in long-term care facilities related to prevention and detection of non-catheter-related urinary tract infections. Results indicate that the education presentation improved knowledge in specific.


Relation between HLA-B27 and clinical features in patients with yersinia arthritis.
A study of 74 yersinia arthritis patients implied that the clinical picture of the disease may be modified by genetic background associated with the histocompatibility antigen B27 (HLA-B27). Sixty-six percent of patients were B27 positive. Joint symptoms were somewhat more severe in B27+ patients. Iritis, conjunctivitis, carditis, signs of urologic inflammation, and complete Reiter's triad occurred only in the B27 + group, whereas erythema nodosum was more common in B27 - group. Several B27 + patients also had "B27 + rheumatic diseases," such as ankylosing spondylitis or Reiter's disease, in their history.


The relationship between sleep and cognition in Parkinson's disease: A meta-analysis.
It is well established that sleep disorders have neuropsychological consequences in otherwise healthy people. Studies of night-time sleep problems and cognition in Parkinson's disease (PD), however, paint a mixed picture, with many reporting no relationship between sleep problems and neuropsychological performance. This review aimed to meta-analyse this research and to examine the factors underlying these mixed results. A literature search was conducted of published and unpublished studies, resulting in 16 papers that met inclusion criteria. Data were analysed in the domains of: global cognitive function; memory (general, long-term verbal recognition, long-term verbal recall); and executive function (general, shifting, updating, inhibition, generativity, fluid reasoning). There was a significant effect of sleep on global cognitive function, long-term verbal recall, long-term verbal recognition, shifting, updating, generativity, and fluid reasoning. Although there are effects on memory and executive function associated with poor sleep in PD, the effects were driven by a small number of studies. Numerous methodological issues were identified. Further studies are needed reliably to determine whether disturbed sleep impacts on cognition via mechanisms of hypoxia, hypercapnia, sleep fragmentation, chronic sleep debt or decreased REM and/or slow wave sleep in PD, as this may have important clinical implications.


AEBP1 Promotes Glioblastoma Progression and Activates the Classical NF-κB Pathway.
Our study was aimed at investigating the mechanistic consequences of the upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in glioblastoma (GBM). The expression of AEBP1 in GBM was assessed by bioinformatics analysis and qRT-PCR; the effects of AEBP1 on GBM cell proliferation, migration, invasion, and tumor growth in vitro and in vivo were detected by a CCK-8 assay, colony formation assay, scratch assay, Transwell assay, and subcutaneous tumor formation, respectively. The activation of related signaling pathways was monitored using western blot. Tumor-related databases and bioinformatics analysis revealed that AEBP1 was highly expressed in GBM and indicated poor outcome of patients; its high expression that was also confirmed in GBM tissues and cell lines was closely related to the tumor size. The results of in vitro experiments showed that AEBP1 could significantly promote GBM cell proliferation, migration, and invasion; in vivo experiments suggested that AEBP1 could contribute to the growth of GBM tumors. AEBP1 could upregulate the level of IκBα phosphorylation, decrease IκBα expression, activate the NF-κB signaling pathway, and promote the expression of downstream oncogenes. Upregulated AEBP1 in GBM promotes GBM cell proliferation, migration, and invasion and facilitates tumor growth in vivo by activating the classical NF-κB pathway.


Gold bipyramids molecularly imprinted gel colorimetric device for whole blood cholesterol analysis.
Simple and disposable monitoring of blood is usually the best solution for early clinical diagnosis and home self-inspection of the chronic patients. Herein, a simple point-of-care (POC) device which called molecularly imprinted membrane modified gel colorimetric device (MIMGCD) was prepared for whole blood cholesterol colorimetric detection at the first time. The convenient detection principle of this device rely on molecularly imprinted membranes for specifically separating cholesterol from whole blood firstly, following the gold bipyramids (GBPs) agarose gel system is react with the cholesterol oxidation to product hydrogen peroxide (H2O2), and the cholesterol will be quantified based on the color change. Under optimal conditions, the analytical performance of the proposed device yielded a linear range of 315.8-6000.0 μM and detection limit of 94.7 μM with 6.89% RSD for cholesterol, which can meet the needs of the detection of normal cholesterol content in the human body. Compared with the traditional whole blood detection methods, no complex sample preparation steps or precision instruments are required, endowing MIMGCD with the merits of easy to operate and low-cost. In addition, the multicolor variation of GBPs in the device allow a colorimetric card-like detection mechanism, which can be used for home self-inspection. This device has the potential to be utilized in clinical and home POC testing application for whole blood biomolecule analysis, thereby facilitating the whole blood screening and long-term monitoring in non-specialized laboratory infrastructure.


Socially driven eating and restriction in the eating disorders.
The aims of this study were: to develop a measure to examine the relationship between socially driven eating and specific eating behaviours; to examine whether different social situations increase or decrease eating in different diagnostic groups; and to determine whether dimensional links exist between responses to social triggers and different aspects of eating pathology. A clinical group of 107 eating-disordered women and 143 nonclinical women completed a measure of socially driven eating and restriction (the Social Eating Scale, or SES) and the Eating Disorders Inventory. The SES had good psychometric properties. Patients with binge-eating disorder (BED) ate more in all social situations, while those with anorexia nervosa ate less. In contrast, bulimia nervosa (BN) patients ate more in general social situations but less in situations where the social trigger was related to food, shape, or weight. There were consistent dimensional links between responses to social triggers and different aspects of eating pathology. These findings support the recent literature on social triggers of eating behaviours but stress the relevance of the mixed pathology of women with BN. The role of social triggers for eating might help to explain the effectiveness of interpersonal psychotherapy when applied to the eating disorders.


Physiological, biochemical, and morphological characteristics of myocardial anoxia: the use of a semi-perfusion canine preparation.
Regional myocardial anoxia was produced in dogs by perfusion of the left circumflex artery (LCA) with deoxygenated blood. Isolated sarcoplasmic reticulum fragments (cardiac relaxing system) showed decreased Ca2+ binding and uptake. The ability of isolated mitochondria to utilise long-chain fatty acids was markedly reduced. This model has revealed inherent biochemical differences between ischaemia and anoxia.


IgG and IgM antibodies immunoreacting with a 2,3-diacyl trehalose-2'-sulphate in sera from leprosy patients.
The distribution of IgG and IgM antibodies immunoreacting with the sulpholipid I (SLI) and sulpholipid IV (SLIV) of Mycobacterium tuberculosis was examined in sera from leprosy patients. It was found that the immunological reactions correlated with the clinical spectrum of leprosy; and in multibacillary patients, antibody titres declined in response to successful treatment. The serological patterns were similar to the PGL I patterns, however, the IgG responses towards the sulpholipids were predominant over the IgM responses in the case of the sulpholipid antigens.