The influence of orthodontic treatment on dental caries: An Australian cohort study.
To assess the influence of orthodontic treatment on long-term caries experience in 30-year-old South Australians. The research hypothesis that was tested was that those with previous orthodontic treatment would have lower caries experience. In 2005-2006, a sample of 1859 30-year-olds from Adelaide, South Australia, who comprised 47% of participants who had previously taken part in an oral epidemiology study in 1988-1989, were traced from the Australian electoral roll and invited to participate in a cross-sectional study investigating long-term dental health outcomes. Participants completed a questionnaire that collected information on socio-demographic characteristics, dental health behaviours and receipt of orthodontic treatment. This was followed by clinical examination. The outcome variables were the summed decayed, missing and filled teeth (DMFT) score, and its individual components. Data were analysed using negative binomial regression. The response rate for the questionnaire was 34% (n = 632). There were no systematic differences between those who were followed up and those who were not followed up. Clinical data for 448 participants were available for analyses, representing 24% of the originally contacted individuals. By the age of 30, over a third of participants had received orthodontic treatment. Regardless of initial malocclusion classification, orthodontically treated participants had a lower DMFT score at age 30 but this did not reach statistical significance. Adjusted models controlling for socio-demographic, dental health behaviour and malocclusion status showed no associations between orthodontic treatment and decayed (Exp B: 1.00, 95% CI: 0.72-1.40), missing (Exp B: 1.00, 95% CI: 0.59-1.69), or filled teeth (Exp B: 1.18, 95% CI: 0.93-1.51) or overall DMFT (Exp B: 1.12, 95% CI: 0.88-1.41). There was no difference in the long-term caries experience of South Australians aged 30 years based on past orthodontic treatment. Our study does not support the contention that those treated orthodontically have better dental health later in life.


Comprehensive identification of mRNA isoforms reveals the diversity of neural cell-surface molecules with roles in retinal development and disease.
Genes encoding cell-surface proteins control nervous system development and are implicated in neurological disorders. These genes produce alternative mRNA isoforms which remain poorly characterized, impeding understanding of how disease-associated mutations cause pathology. Here we introduce a strategy to define complete portfolios of full-length isoforms encoded by individual genes. Applying this approach to neural cell-surface molecules, we identify thousands of unannotated isoforms expressed in retina and brain. By mass spectrometry we confirm expression of newly-discovered proteins on the cell surface in vivo. Remarkably, we discover that the major isoform of a retinal degeneration gene, CRB1, was previously overlooked. This CRB1 isoform is the only one expressed by photoreceptors, the affected cells in CRB1 disease. Using mouse mutants, we identify a function for this isoform at photoreceptor-glial junctions and demonstrate that loss of this isoform accelerates photoreceptor death. Therefore, our isoform identification strategy enables discovery of new gene functions relevant to disease.


Are clinical features in Löfgren's syndrome-related erythema nodosum different from idiopathic erythema nodosum?
We retrospectively evaluated acute sarcoidosis (Löfgren's syndrome) patients diagnosed at 2 centers and compared the clinical features of Löfgren's syndrome (LS) related erythema nodosum (EN) to patients with idiopathic IEN who were diagnosed within the same time frame. Thirty patients (10 males, 20 females) who were diagnosed with LS and were being followed up for the last 8 years at 2 centers were included. Thirty patients (4 males, 26 females) who were admitted to the rheumatology outpatient clinics for IEN during that time period were taken as controls. The clinical and laboratory features at the initial admission, treatment modalities and response were recorded. Twentyfour (80%) patients with LS related EN had arthritis and/or arthralgia. Fifteen of them had only findings of periarticular ankle inflammation and 4 had polyarthritis. When LS related EN patients were compared to IEN patients, the former group had more arthritis and/or arthralgia (p < 0.001), leucocytosis (p = 0.02), lymphopenia (p = 0.005) and thrombocytosis (p = 0.05), and higher ESR (p = 0.02). Twentyfive (83.3%) patients with LS related EN were administered oral corticosteroids. In 21 patients, hilar lymphadenopathy disappeared on control chest x-ray and CT; in 3 patients, minimal residual lymph node enlargement was persistent. During a median follow-up of 54 months (range: 10-84 months), none of the LS related EN patients had clinical relapse. Apart from BHL, arthritis and/or arthralgia especially periarticular ankle inflammation is the feature which could be used to differentiate LS related EN from IEN. There is more need for steroids in LS patients and the symptoms quickly resolve with steroids.


[Intracellular glucose oxidase from Penicillium funiculosum 46.1].
A method for isolating extracellular glucose oxidase from the fungus Penicillium funiculosum 46.1, using ultrafiltration membranes, was developed. Two samples of the enzyme with a specific activity of 914-956 IU were obtained. The enzyme exhibited a high catalytic activity at pH above 6.0. The effective rate constant of glucose oxidase inactivation at pH 2.6 and 16 degrees C was 2.74 x 10(-6) s-1. This constant decreased significantly as pH of the medium increased (4.0-10.0). The temperature optimum for glucose oxidase-catalyzed beta-D-glucose oxidation was in the range 30-65 degrees C. At temperatures below 30 degrees C, the activation energy for beta-D-glucose oxidation was 6.42 kcal/mol; at higher temperatures, this parameter was equal to 0.61 kcal/mol. Kinetic parameters of glucose oxidase-catalyzed delta-D-glucose oxidation depended on the initial concentration of the enzyme in the solution. Glucose oxidase also catalyzed the oxidation of 2-deoxy-D-glucose, maltose, and galactose.


Genetic examination of initial amino acid oxidation and glutamate catabolism in the hyperthermophilic archaeon Thermococcus kodakarensis.
Amino acid catabolism in Thermococcales is presumed to proceed via three steps: oxidative deamination of amino acids by glutamate dehydrogenase (GDH) or aminotransferases, oxidative decarboxylation by 2-oxoacid:ferredoxin oxidoreductases (KOR), and hydrolysis of acyl-coenzyme A (CoA) by ADP-forming acyl-CoA synthetases (ACS). Here, we performed a genetic examination of enzymes involved in Glu catabolism in Thermococcus kodakarensis. Examination of amino acid dehydrogenase activities in cell extracts of T. kodakarensis KUW1 (ΔpyrF ΔtrpE) revealed high NADP-dependent GDH activity, along with lower levels of NAD-dependent activity. NADP-dependent activities toward Gln/Ala/Val/Cys and an NAD-dependent threonine dehydrogenase activity were also detected. In KGDH1, a gene disruption strain of T. kodakarensis GDH (Tk-GDH), only threonine dehydrogenase activity was detected, indicating that all other activities were dependent on Tk-GDH. KGDH1 could not grow in a medium in which growth was dependent on amino acid catabolism, implying that Tk-GDH is the only enzyme that can discharge the electrons (to NADP(+)/NAD(+)) released from amino acids in their oxidation to 2-oxoacids. In a medium containing excess pyruvate, KGDH1 displayed normal growth, but higher degrees of amino acid catabolism were observed compared to those for KUW1, suggesting that Tk-GDH functions to suppress amino acid oxidation and plays an anabolic role under this condition. We further constructed disruption strains of 2-oxoglutarate:ferredoxin oxidoreductase and succinyl-CoA synthetase. The two strains displayed growth defects in both media compared to KUW1. Succinate generation was not observed in these strains, indicating that the two enzymes are solely responsible for Glu catabolism among the multiple KOR and ACS enzymes in T. kodakarensis.


Minimal Fluoroscopic Catheter Ablation for Adult Patients with Paroxysmal Supraventricular Tachycardia without the Assistance of Intracardiac Echocardiography.
Radiation exposure during fluoroscopic procedures increases the risk of cancer for both patients and operators. The aim of this study was to investigate the safety and efficacy of adopting a three-dimensional electroanatomical mapping (3D EAM) system during ablation for paroxysmal supraventricular tachycardia (PSVT), without the assistance of intracardiac echocardiography (ICE), for both right- and left-chamber cardiac procedures. We retrospectively enrolled all patients with PSVT from September 2018 to December 2020. The patients were grouped according to the use of the 3D EAM system (3D-guided group, n = 102 vs. conventional group, n = 226). The acute success rates were high in both groups (100% vs. 99.1%). The fluoroscopy time was significantly lower in the 3D-guided group than in the conventional group (2.4 ± 4.4 vs. 19.0 ± 10.8 min); the procedure time was significantly increased in the 3D-guided group (104.5 ± 29.9 vs. 94.0 ± 31.9 min), and this was associated with the post-electrophysiology test diagnosis after adjustment for multiple variables [standardized B coefficient (β) 0.188]. There was no learning curve for each electrophysiologist in terms of fluoroscopy and procedure times. The 3D EAM system, without the assistance of ICE, was safe and effective in guiding PSVT ablation in both left- and right-chamber ablation.


Genomic Contraindications for Heart Transplantation.
Genome sequencing raises new ethical challenges. Decoding the genome produces new forms of diagnostic and prognostic information; however, the information is often difficult to interpret. The connection between most genetic variants and their phenotypic manifestations is not understood. This scenario is particularly true for disorders that are not associated with an autosomal genetic variant. The analytic uncertainty is compounded by moral uncertainty about how, exactly, the results of genomic testing should influence clinical decisions. In this Ethics Rounds, we present a case in which genomic findings seemed to play a role in deciding whether a patient was to be listed as a transplant candidate. We then asked experts in bioethics and cardiology to discuss the implications of such decisions.


Cardiovascular effects of felypressin.
Cardiovascular effects of felypressin (FEL) were studied in Wistar rats. Heart rate and mean arterial pressure measurements were taken in awake rats treated with vasopressin (AVP), FEL, or epinephrine (EPI). Each group received either an intravenous (IV) or an intracerebroventricular V1 receptor antagonist, saline, area postrema removal, or sham surgery. Analysis of variance and Student-Newman-Keuls (P < .05) were applied. Felypressin and AVP induced a pressor effect, and bradycardia was inhibited by IV V1 antagonist. Intracerebroventricular V1 antagonist and area postrema removal enhanced their pressor effects. Epinephrine induced a higher pressor effect and a similar bradycardia that was not affected by the treatments. It was concluded that FEL depends on V1 receptors to induce pressor and bradycardic effects, and that it produces a high relationship between bradycardia and mean arterial pressure variation depending on area postrema and central V1 receptors. These effects are potentially less harmful to the cardiovascular system than the effects of EPI.


[Protective effect of 2,4-dihydroxybenzophenone on cocaine-induced hepatotoxicity and neurotoxicity in mice].
To investigate the protective effect of 2,4-dihydroxybenzophenone(BP-1) on acute hepatotoxicity and neurotoxicity induced by cocaine in mice, and its possible mechanism. Male ICR mice were pretreated with BP-1(100,200,400 mg/kg, ig, 4 d), cocaine(75 mg/kg) was injected 30 minutes after BP-1 administration on day 4.Twenty-four hours after the injection of cocaine, the serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed by HITACHI-7170A automatic analyzer. The content of malondialdehyde (MDA) and the content of reduced glutathione (GSH) and oxidized glutathione (GSSG) were examined, and the ratio of GSH/GSSG was calculated, and histopathological analyses were also made. Male ICR mice were pretreated with BP-1(100,200,400 mg/kg, ig, 3 d), cocaine(20 mg/kg) was injected 30 minutes after BP-1 administration on day 3.The locomotor activity during 0-180 minutes of mice was recorded individually for each animal immediately after cocaine injection. After the administration of cocaine, compared with corresponding solvent group, the activities of ALT [(1 571±1 161) IU/L vs. (30±16) IU/L, P<0.05], AST [(408±226) IU/L vs. (101±12) IU/L, P<0.05] and LDH [(3 963±1 431) IU/L vs. (1 935±287) IU/L, P<0.05] were significantly increased; the ratio of GSH/GSSG [(5.11±0.63) vs. (6.88±1.13),P<0.05] was decreased and the content of MDA [(1.97±1.36) μ mol/g vs. (0.07±0.06) μmol/g, P<0.01] was significantly increased. With the pretreatment of BP-1, compared with cocaine treatment group, the serum ALT [(112±96 )IU/L, (54±20) IU/L, (35±15) IU/L, P<0.05],AST [(130±33) IU/L,(107±5) IU/L, (99±9) IU/L, P<0.05] and LDH [(1 667±564) IU/L, (1 507±365) IU/L, (1 249±349) IU/L, P<0.01] were significantly decreased, the ratios of GSH/GSSG [(7.33±1.84), (9.28±0.67), (10.5±1.20), P<0.05] were increased and the contents of MDA [(1.82±1.19)μmol/g, (0.49±0.31)μmol/g, (0.35±0.30) μmol/g, P<0.05] were decreased. Significant amelioration in liver histopathology was also presented in the BP-1 treatment groups. The BP-1 pretreated mice showed significant reduction in activity counts evoked by cocaine (20 mg/kg), and shorten the time for activity counts to become normal. BP-1 has protective effect on acute hepatotoxicity and neurotoxicity of mice induced by cocaine. Its mechanisms might be associated with its antioxidant activity.


An application of partial least squares for identifying dietary patterns in bone health.
In a large cohort of older women, a mechanism-driven statistical technique for assessing dietary patterns that considers a potential nutrient pathway found two dietary patterns associated with lumbar spine and femoral neck bone mineral density. A "healthy" dietary pattern was observed to be beneficial for bone mineral density. Dietary patterns represent a broader, more realistic representation of how foods are consumed, compared to individual food or nutrient analyses. Partial least-squares (PLS) is a data-reduction technique for identifying dietary patterns that maximizes correlation between foods and nutrients hypothesized to be on the path to disease, is more hypothesis-driven than previous methods, and has not been applied to the study of dietary patterns in relation to bone health. Women from the Aberdeen Prospective Osteoporosis Screening Study (2007-2011, n = 2129, age = 66 years (2.2)) provided dietary intake using a food frequency questionnaire; 37 food groups were created. We applied PLS to the 37 food groups and 9 chosen response variables (calcium, potassium, vitamin C, vitamin D, protein, alcohol, magnesium, phosphorus, zinc) to identify dietary patterns associated with bone mineral density (BMD) cross-sectionally. Multivariable regression was used to assess the relationship between the retained dietary patterns and BMD at the lumbar spine and femoral neck, adjusting for age, body mass index, physical activity level, smoking, and national deprivation category. Five dietary patterns were identified, explaining 25% of the variation in food groups and 77% in the response variables. Two dietary patterns were positively associated with lumbar spine (per unit increase in factor 2: 0.012 g/cm2 [95% CI: 0.006, 0.01]; factor 4: 0.007 g/cm2 [95% CI: 0.00001, 0.01]) and femoral neck (factor 2: 0.006 g/cm2 [95% CI: 0.002, 0.01]; factor 4: 0.008 g/cm2 [95% CI: 0.003, 0.01)]) BMD. Dietary pattern 2 was characterized by high intakes of milk, vegetables, fruit and vegetable juices, and wine, and low intakes of processed meats, cheese, biscuits, cakes, puddings, confectionary, sweetened fizzy drinks and spirits while dietary pattern 4 was characterized by high intakes of fruits, red and white meats, and wine, and low intakes of vegetables and sweet spreads. Our findings using a robust statistical technique provided important support to initiatives focusing on what constitutes a healthy diet and its implications.


Limited role of inducible nitric oxide synthase in blood-brain barrier function after experimental subarachnoid hemorrhage.
Excessive nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) may play a pivotal role in blood-brain barrier (BBB) breakdown following subarachnoid hemorrhage (SAH). We investigated if the inhibition of iNOS could reduce BBB breakdown and cerebral edema, thereby leading to improved outcome 24 h after SAH. Forty male rats were assigned to three groups: control, SAH, and treatment groups. SAH was induced by perforating the bifurcation of the internal carotid artery. The neurological score and the mortality were evaluated 24 h after the surgery. The expression of iNOS, the concentration of NO metabolites, morphological changes in neuronal cells, water content, and IgG leakage were also evaluated. The expression of iNOS, as well as the concentration of NO metabolites, was elevated after SAH. Treatment with p-Toluenesulfonate decreased both the expression of iNOS and the concentration of NO metabolites. However, there was no significant change in water content, BBB disruption, or morphological findings between the SAH group and the treatment group. Furthermore no significant differences in neurological score or mortality were observed. The iNOS inhibitor failed to reduce BBB breakdown, brain edema, and neuronal cell death and failed to improve the neurological score and the mortality 24 h after SAH.


Human T-cell leukemia virus type 1 Tax and cellular transformation.
Infection of T-cells by human T-cell leukemia virus type 1 (HTLV-1) causes a lymphoproliferative malignancy known as adult T-cell leukemia (ATL). ATL is characterized by abnormal lymphocytes, called flower cells, which have cleaved and convoluted nuclei. Tax, encoded by the HTLV-1 pX region, is a critical nonstructural protein that plays a central role in leukemogenesis; however, the mechanisms of HTLV-1 oncogenesis have not been clarified fully. In this review, we summarize current thinking on how Tax may affect ATL leukemogenesis.


Upward spirals of positive emotions counter downward spirals of negativity: insights from the broaden-and-build theory and affective neuroscience on the treatment of emotion dysfunctions and deficits in psychopathology.
This review integrates Fredrickson's broaden-and-build theory of positive emotions with advances in affective neuroscience regarding plasticity in the neural circuitry of emotions to inform the treatment of emotion deficits within psychopathology. We first present a body of research showing that positive emotions broaden cognition and behavioral repertoires, and in so doing, build durable biopsychosocial resources that support coping and flourishing mental health. Next, by explicating the processes through which momentary experiences of emotions may accrue into self-perpetuating emotional systems, the current review proposes an underlying architecture of state-trait interactions that engenders lasting affective dispositions. This theoretical framework is then used to elucidate the cognitive-emotional mechanisms underpinning three disorders of affect regulation: depression, anxiety, and schizophrenia. In turn, two mind training interventions, mindfulness and loving-kindness meditation, are highlighted as means of generating positive emotions that may counter the negative affective processes implicated in these disorders. We conclude with the proposition that positive emotions may exert a countervailing force on the dysphoric, fearful, or anhedonic states characteristic of psychopathologies typified by emotional dysfunctions.


The use of halofuginone in limiting urethral stricture formation and recurrence: an experimental study in rabbits.
We developed a reproducible animal model for the induction of urethral stricture in the rabbit and evaluated the role of halofuginone in limiting stricture formation. A total of 20 New Zealand male rabbits were used in the first phase of the experiment. Bulbar urethral stricture was induced by electrocoagulation. The animals were then randomly assigned to 2 groups of 10 each, which received a diet containing halofuginone or a normal diet. In the second phase electrocoagulation induced stricture was treated with visual internal urethrotomy in 45 rabbits. These rabbits were randomly assigned to 2 groups, namely a halofuginone and a control group. In the first phase stricture developed in 2 study rabbits (20%) vs 10 controls (100%). In the second phase 37 rabbits were evaluable (8 died). Recurrent stricture was observed in 5 of the 18 study rabbits (27%) vs 14 of the 19 controls (73%). Halofuginone is effective in limiting the occurrence of de novo urethral stricture and recurrent stricture after visual internal urethrotomy. This antifibrotic molecule may become an important therapy to treat urethral stricture and/or recurrence following endoscopic manipulation of stricture in humans.


Hormonal and nonhormonal desensitization in isolated bone cells.
Prior exposure to PTH markedly decreased the responsiveness of isolated, cultured bone cells to the stimulatory effect of the hormone on cyclic AMP formation. This process of desensitization developed within 30 min, persisted during prolonged incubation of the cells in PTH-free medium, and could not be attributed to enhanced excretion of cyclic AMP from the cells, nor to the extracellular accumulation of an inhibitor of PTH action. Adenylate cyclase activity in a subcellular fraction derived from PTH-treated cells was refractory to PTH and to sodium fluoride. These results indicate that PTH-mediated desensitization reflects, at least in part, impaired cyclic AMP formation. Adenosine and PGE2, known stimulators of bone cell cyclic AMP formation, elicited agonist-specific desensitization, and also desensitized bone cells to the effects of subsequently added PTH. PTH blunted the cellular response to adenosine, but not to PGE2. Modest refractoriness to PTH was evident in cells that had been treated previously with the cyclic AMP phosphodiesterase inhibitors IBMX, theophylline, and Bt2cAMP, whereas treatment with sodium butyrate had no effect. The actions of the inhibitors, like that of PTH, were rapid in onset and long-lasting. Desensitization caused by previous treatment with the phosphodiesterase inhibitors, and with PTH itself, was accompanied by enhanced phosphodiesterase activity in bone cell homogenates. Induction of phosphodiesterase activity may well contribute to desensitization in the bone cell system.


[Ventilatory adaptations for breath holding in divers].
The length of breath-hold duration in divers is dependant on a number of interacting variables which include mechanical factors (lung volumes), chemical factors (sensitivity to hypoxia and hypercapnia), non-chemical factors (involuntary muscular contractions), psychological factors (motivation, stress, competition) and various extrinsic factors (training, muscular exercise). These stimulus provoke the unpleasant sensation of an urge to breathe at the termination point of the breath hold. Training and experience produces adaptations in divers which decreases sensitivity to CO(2) and which delays and minimises the involuntary contractions of respiratory muscles provoked by the absence of respiratory movements. These adaptations modify the breaking point of, and increase the duration of breath holding. Godfrey & Campbell's model (1968), modified by Courteix et coll. (1993) and Delapille (2000), attempts to explain the control of breathing in the context of apnea and to define the effects of each of these stimulus on the respiratory activity of divers and non-divers.


Does Type D Personality Impact on the Prognosis of Patients Who Underwent Catheter Ablation for Atrial Fibrillation? A 1-Year Follow-Up Study.
Although Type D personality has been associated with the prognosis of various cardiac diseases, few studies have investigated the influence of Type D personality on the cardiac and psychiatric prognoses of patients with atrial fibrillation (AF). Depression, anxiety, and quality of life were measured at baseline and 6 months. The recurrence of AF was measured during 1-year following radiofrequency catheter ablation (RFCA) for AF. The Kaplan-Meier method with log-rank tests were used to compare the cumulative recurrence of AF. ACox proportional hazard model was conducted to identify factors that contribute to the recurrence of AF. A total of 236 patients admitted for RFCA were recruited. Patients with a Type D personality had higher levels of depression and anxiety and a poorer quality of life compared to controls. Although depression, anxiety, and quality of life had improved 6 months after RFCA, significant differences in psychiatric symptoms remained between patients with and without Type D personality. In the Cox models, the type of AF was the only factor that influenced the recurrence of AF. Our results suggest that Type D personality predominately influences psychological distress in patients with AF, but not the recurrence of AF.


The 65,000-Mr DNA-binding and virion trans-inducing proteins of herpes simplex virus type 1.
The possible identity of the herpes simplex virus type 1 (HSV-1) 65K (65,000-Mr) virion protein which stimulates transcription from immediate-early genes with the HSV-1 65K DNA-binding protein was investigated. The two proteins were found to be distinct by the three separate criteria of immunological reactivity, tryptic peptide fingerprinting, and mobility in two-dimensional gels. Using HSV-1/HSV-2 intertypic recombinants and a serotype-specific antiserum, we located the gene encoding the 65K DNA-binding protein between coordinates 0.574 and 0.682 on the HSV-1 genome. The protein is posttranslationally modified by phosphorylation. In crude extracts of HSV-1-infected cells the 65K trans-inducing protein did not detectably bind to double-stranded calf thymus DNA under the conditions of our assay.


Heat-induced native dimerization prevents amyloid formation by variable domain from immunoglobulin light-chain REI.
Amyloid light-chain (AL) amyloidosis is a protein-misfolding disease characterized by accumulation of immunoglobulin light chains (LCs) into amyloid fibrils. Dimerization of a full length or variable domain (VL ) of LC serves to stabilize the native state and prevent the formation of amyloid fibrils. We here analyzed the thermodynamic properties of dimerization and unfolding reactions by nonamyloidogenic VL from REI LC or its monomeric Y96K mutant using sedimentation velocity and circular dichroism. The data indicate that the equilibrium shifts to native dimerization for wild-type REI VL by elevating temperature due to the negative enthalpy change for dimer dissociation (-81.2 kJ·mol-1 ). The Y96K mutation did not affect the stability of the monomeric native state but increased amyloidogenicity. These results suggest that the heat-induced native homodimerization is the major factor preventing amyloid formation by wild-type REI VL . Heat-induced native oligomerization may be an efficient strategy to avoid the formation of misfolded aggregates particularly for thermostable proteins that are used at elevated temperatures under conditions where other proteins tend to misfold. Structural data are available in the Protein Data Bank under the accession numbers 5XP1 and 5XQY.


The Ms. Olsen test: Measurement properties of a short test of nursing staffs' competence in clinical decision-making.
To assess the measurement properties of the Ms. Olsen test for registered nurses and assistant nurses, respectively, and suggest cut-off points between competence levels. Cross-sectional study. The results were analysed by implementing the Rasch Measurement Theory. Nursing staff working in various health care settings participated (n = 757). To measure the competence of nursing staff in clinical decision-making, a 19-item scale from the Nursing Older People-Competence Evaluation Tool-the 'Ms. Olsen test'-was used. Data were collected in October 2017, 2018 and 2019. The Ms. Olsen test showed reasonably good measurement properties for registered nurses and assistant nurses respectively. Results show slightly better measurement properties for registered nurses than for assistant nurses. The cut-off for registered nurses, 0.62, corresponds to managing approximately two-thirds of the items while, for assistant nurses, the cut-off of 0.01 corresponds to managing approximately half of the items. The Ms. Olsen test is a short (7- to 10-min) test measuring competence in clinical decision-making among nursing staff working in older people nursing. Despite reasonably good measurement properties, this should be considered an initial validation in the development of a short test for assessing clinical decision-making among nursing staff in various health care setting. Several scales aiming to measure nursing competence have been developed over the last decade, but measurement properties (beyond classical test theory) are seldom evaluated, few scales concern other staff groups than registered nurses and few scales have proposed or established cut-offs for safe practice. The Ms. Olsen test is a short test of clinical decision-making that demonstrates reasonably good measurement properties. Cut-off points for registered nurses and assistant nurses were established. The Ms. Olsen test may be used to measure and evaluate competence in clinical decision-making among nursing staff working in older people nursing and educational settings.


The patient: Emerging clinical applications of intravenous immunoglobulin.
Intravenous immunoglobulin (IGIV) originally was used as prophylactic treatment of infections in patients with primary immunodeficiency disease. Today, administration of IGIV, due in large part to its immunomodulatory activity, has expanded to include a number of other disorders. Available data suggest that the accepted indications for IGIV will continue to expand. As the number of clinical applications for this therapy grows, so will market opportunities; current preparations will be modified and improved and new products introduced. Intravenous immunoglobulin therapy has improved the lives of many patients with immune-related disorders. Future applications will ideally advance this paradigm further.


Characterization of 2-bromoethanesulfonate as a selective inhibitor of the coenzyme m-dependent pathway and enzymes of bacterial aliphatic epoxide metabolism.
Bacterial growth with short-chain aliphatic alkenes requires coenzyme M (CoM) (2-mercaptoethanesulfonic acid), which serves as the nucleophile for activation and conversion of epoxide products formed from alkene oxidation to central metabolites. In the present work the CoM analog 2-bromoethanesulfonate (BES) was shown to be a specific inhibitor of propylene-dependent growth of and epoxypropane metabolism by Xanthobacter autotrophicus strain Py2. BES (at low [millimolar] concentrations) completely prevented growth with propylene but had no effect on growth with acetone or n-propanol. Propylene consumption by cells was largely unaffected by the presence of BES, but epoxypropane accumulated in the medium in a time-dependent fashion with BES present. The addition of BES to cells resulted in time-dependent loss of epoxypropane degradation activity that was restored upon removal of BES and addition of CoM. Exposure of cells to BES resulted in a loss of epoxypropane-dependent CO(2) fixation activity that was restored only upon synthesis of new protein. Addition of BES to cell extracts resulted in an irreversible loss of epoxide carboxylase activity that was restored by addition of purified 2-ketopropyl-CoM carboxylase/oxidoreductase (2-KPCC), the terminal enzyme of epoxide carboxylation, but not by addition of epoxyalkane:CoM transferase or 2-hydroxypropyl-CoM dehydrogenase, the enzymes which catalyze the first two reactions of epoxide carboxylation. Comparative studies of the propylene-oxidizing actinomycete Rhodococcus rhodochrous strain B276 showed that BES is an inhibitor of propylene-dependent growth in this organism as well but is not an inhibitor of CoM-independent growth with propane. These results suggest that BES inhibits propylene-dependent growth and epoxide metabolism via irreversible inactivation of the key CO(2)-fixing enzyme 2-KPCC.


[Overexpression of fibroblast growth factor receptor like 1 (FGFRL1) inhibits proliferation and migration of HCT116 human colon cancer cells, and promotes their apoptosis].
Objective To investigate the effect of fibroblast growth factor receptor like 1 (FGFRL1) overexpression on the biological behavior of HCT116 human colon cancer cell line. Methods A recombinant plasmid, named as pcDNA3.1-FGFRL1 which expresses FGFRL1 in mammal cells, was constructed. After a transfection of HCT116 cells with pcDNA3.1-FGFRL1, the stable expression cell line was obtained via continual selection with G418, and FGFRL1 expression was analyzed by real time quantitative PCR and Western blotting. In the following experiment, cells were divided into three groups: the blank group (untreated HCT116 cells), the negative group (empty vector stably transfected cells) and the experience group (pcDNA3.1-FGFRL1 stably transfected cells). Cell proliferation was detected by CCK-8 assay. Cell migration ability was analyzed with TranswellTM assay and their apoptosis was evaluated by flow cytometry. Results FGFRL1 mRNA and protein levels increased significantly in FGFRL1 overexpression group. After the overexpression of FGFRL1, proliferation and migration of HCT116 cells dropped significantly, while their apoptosis increased significantly. Conclusion Overexpression of FGFRL1 inhibits the proliferation and migration of colon cancer HCT116 cells and promotes their apoptosis.


Sagittal-lung CT measurements in the evaluation of asthma-COPD overlap syndrome: a distinctive phenotype from COPD alone.
This study aimed at investigating the capability of sagittal-lung computed tomography (CT) measurements in differentiating chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome (ACOS). Clinical and high-resolution CT of 229 patients including 123 pure COPD patients and 106 ACOS patients were included. Sagittal-lung CT measurements in terms of bilateral lung height (LH), anterior-posterior lung diameter (APLD), diaphragm height (DH), and anterior sterno-diaphragmatic angle (ASDA), as well as inter-pulmonary septum length (IPSL) on axial images were measured both before and after bronchodilator (BD) administration. Comparisons of clinical characteristics and CT measurements between patient groups were performed. All pre-BD quantitative sagittal features measuring diaphragm flattening and hyperinflation were not significantly different between patients with COPD and patients with ACOS (P values all >0.05). Following BD administration, the ACOS patients exhibited lower left LH, bilateral APLD, and bilateral ASDA, but higher right DH, compared to pure COPD patients (P values all <0.05). Right LH, left DH and IPSL were not significantly different between patient groups. Besides, variations of all sagittal-lung CT measurements were significantly larger in patients with ACOS than in patients with pure COPD (P values all <0.001) and showed high performance in differentiating these two kinds of patient, with diagnostic sensitivities ranging from 76.4 to 97.2%, specificities ranging from 86.2 to 100.0%, and accuracies ranging from 80.9 to 90.7%. Sagittal-lung CT measurements allow for differentiating patients with ACOS from those with pure COPD. The ACOS patients had larger post-BD variations of sagittal-lung CT measurements than patients with pure COPD.


Molecular dynamics simulation of the capillary leveling of viscoelastic polymer films.
Surface tension-driven flow techniques have recently emerged as an efficient means of shedding light into the rheology of thin polymer films. Motivated by experimental and theoretical approaches in films bearing a varying surface topography, we present results on the capillary relaxation of a square pattern at the free surface of a viscoelastic polymer film, using molecular dynamics simulations of a coarse-grained polymer model. Height profiles are monitored as a function of time after heating the system above its glass-transition temperature and their time dependence is fitted to the theory of capillary leveling. Results show that the viscosity is not constant, but time dependent. In addition to providing a complementary insight about the local inner mechanisms, our simulations of the capillary-leveling process therefore probe the viscoelasticity of the polymer and not only its viscosity, in contrast to most experimental approaches.


Evaluation of a rapid latex slide agglutination test for herpes simplex virus as a specimen screen and culture identification method.
A total of 449 clinical specimens and 199 culture fluids were tested using the Virogen Herpes Slide Test (Wampole Laboratories, Div. Carter-Wallace, Inc., Cranbury, N.J.), a rapid latex agglutination procedure. The results were compared with those obtained with isolation of herpes simplex virus in cell culture followed by identification using immunoperoxidase or fluorescent reagents. The sensitivity, specificity, and positive and negative predictive values of the direct test were 49.7, 93.4, 96.0, and 37.1%, respectively. The sensitivity and specificity of the latex agglutination test for culture confirmation were 75.9 and 100%, respectively.


Genotype Variation in Rice (Oryza sativa L.) Tolerance to Fe Toxicity Might Be Linked to Root Cell Wall Lignification.
Iron (Fe) is an essential element to plants, but can be harmful if accumulated to toxic concentrations. Fe toxicity can be a major nutritional disorder in rice (Oryza sativa) when cultivated under waterlogged conditions, as a result of excessive Fe solubilization of in the soil. However, little is known about the basis of Fe toxicity and tolerance at both physiological and molecular level. To identify mechanisms and potential candidate genes for Fe tolerance in rice, we comparatively analyzed the effects of excess Fe on two cultivars with distinct tolerance to Fe toxicity, EPAGRI 108 (tolerant) and BR-IRGA 409 (susceptible). After excess Fe treatment, BR-IRGA 409 plants showed reduced biomass and photosynthetic parameters, compared to EPAGRI 108. EPAGRI 108 plants accumulated lower amounts of Fe in both shoots and roots compared to BR-IRGA 409. We conducted transcriptomic analyses of roots from susceptible and tolerant plants under control and excess Fe conditions. We found 423 up-regulated and 92 down-regulated genes in the susceptible cultivar, and 42 up-regulated and 305 down-regulated genes in the tolerant one. We observed striking differences in root gene expression profiles following exposure to excess Fe: the two cultivars showed no genes regulated in the same way (up or down in both), and 264 genes were oppositely regulated in both cultivars. Plants from the susceptible cultivar showed down-regulation of known Fe uptake-related genes, indicating that plants are actively decreasing Fe acquisition. On the other hand, plants from the tolerant cultivar showed up-regulation of genes involved in root cell wall biosynthesis and lignification. We confirmed that the tolerant cultivar has increased lignification in the outer layers of the cortex and in the vascular bundle compared to the susceptible cultivar, suggesting that the capacity to avoid excessive Fe uptake could rely in root cell wall remodeling. Moreover, we showed that increased lignin concentrations in roots might be linked to Fe tolerance in other rice cultivars, suggesting that a similar mechanism might operate in multiple genotypes. Our results indicate that changes in root cell wall and Fe permeability might be related to Fe toxicity tolerance in rice natural variation.


Loss of GGN leads to pre-implantation embryonic lethality and compromised male meiotic DNA double strand break repair in the mouse.
The integrity of male germ cell genome is critical for the correct progression of spermatogenesis, successful fertilization, and proper development of the offspring. Several DNA repair pathways exist in male germ cells. However, unlike somatic cells, key components of such pathways remain largely unidentified. Gametogenetin (GGN) is a testis-enriched protein that has been shown to bind to the DNA repair protein FANCL via yeast-two-hybrid assays. This finding and its testis-enriched expression pattern raise the possibility that GGN plays a role in DNA repair during spermatogenesis. Herein we demonstrated that the largest isoform GGN1 interacted with components of DNA repair machinery in the mouse testis. In addition to FANCL, GGN1 interacted with the critical component of the Fanconi Anemia (FA) pathway FANCD2 and a downstream component of the BRCA pathway, BRCC36. To define the physiological function of GGN, we generated a Ggn null mouse line. A complete loss of GGN resulted in embryonic lethality at the very earliest period of pre-implantation development, with no viable blastocysts observed. This finding was consistent with the observation that Ggn mRNA was also expressed in lower levels in the oocyte and pre-implantation embryos. Moreover, pachytene spermatocytes of the Ggn heterozygous knockout mice showed an increased incidence of unrepaired DNA double strand breaks (DSBs). Together, our results suggest that GGN plays a role in male meiotic DSB repair and is absolutely required for the survival of pre-implantation embryos.


Exposure to perfluoroalkyl substances and hyperlipidemia among adults: data from NHANES 2017-2018.
The present study aims to explore the relationship between PFAS exposure and hyperlipidemia using data from NHANES. 1600 subjects were included in the analysis, and 9 kinds of PFAS were measured. Multivariate logistic regression analysis was performed to explore the association between serum PFAS and hyperlipidemia. Compared with the lowest quartile of Sm-PFOS, the percentage change for hyperlipidemia was 57% and 41% in the third and highest quartile of PFOS. The positive association between Sm-PFOS and hyperlipidemia remained significant in population aged <60, and the OR for hyperlipidemia in 4th quartile of Sm-PFOS was 1.81. These findings indicated serum Sm-PFOS was independently associated with a higher risk for hyperlipidemia. The epidemiological study warrants further study to elucidate the causal relationship between them.


Trade-offs in prenatal detection of Down syndrome.
This paper presents the results of different screening policies for prenatal detection of Down syndrome that would allow decision makers to make informed choices. A decision analysis model was built to compare 8 screening policies with regard to a selected set of outcome measures. Probabilities used in the analysis were obtained from official administrative data reports in Spain and Catalonia and from data published in the medical literature. Sensitivity analyses were carried out to test the robustness of screening policies' results to changes in uptake rates, diagnostic accuracy, and resources consumed. Selected screening policies posed major trades-offs regarding detection rates, false-positive results, fetal loss, and costs of the programs. All outcome measures considered were found quite robust to changes in uptake rates. Sensitivity and specificity rates of screening tests were shown to be the most influential factors in the outcome measures considered. The disclosed trade-offs emphasize the need to comprehensively inform decision makers about both positive and negative consequences of adopting one screening policy or another.


Effect of neutral-cushioned running shoes on plantar pressure loading and comfort in athletes with cavus feet: a crossover randomized controlled trial.
High injury rates observed in athletes with cavus feet are thought to be associated with elevated plantar pressure loading. Neutral-cushioned running shoes are often recommended to manage and prevent such injuries. To investigate in-shoe plantar pressure loading and comfort during running in 2 popular neutral-cushioned running shoes recommended for athletes with cavus feet. Controlled laboratory study. Plantar pressures were collected using the in-shoe Novel Pedar-X system during overground running in 22 athletes with cavus feet in 2 neutral-cushioned running shoes (Asics Nimbus 6 and Brooks Glycerin 3) and a control condition (Dunlop Volley). Comfort was measured using a validated visual analog scale. Compared with the control, both neutral-cushioned running shoes significantly reduced peak pressure and pressure-time integrals by 17% to 33% (P < .001). The Brooks Glycerin most effectively reduced pressure beneath the whole foot and forefoot (P < .01), and the Asics Nimbus most effectively reduced rearfoot pressure (P <.01). Both neutral-cushioned running shoes reduced force at the forefoot by 6% and increased it at the midfoot by 12% to 17% (P < .05). Contact time and area increased in both neutral-cushioned running shoes (P < .01). The Asics Nimbus was the most comfortable, although both neutral-cushioned running shoes were significantly more comfortable than the control (P < .001). Two popular types of neutral-cushioned running shoes were effective at reducing plantar pressures in athletes with cavus feet. Regional differences in pressure reduction suggest neutral-cushioned running shoe recommendation should shift from being categorical in nature to being based on location of injury or elevated plantar pressure.


Wound macrophages express TGF-alpha and other growth factors in vivo: analysis by mRNA phenotyping.
The presence of macrophages is required for the regeneration of many cell types during wound healing. Macrophages have been reported to express a wide range of mitogenic factors and cytokines, but none of these factors has been shown in vivo to sustain all the wound-healing processes. It has been suggested that transforming growth factor-alpha (TGF-alpha) may mediate angiogenesis, epidermal regrowth, and formation of granulation tissue in vivo. Macrophages isolated from a wound site, and not exposed to cell culture conditions, expressed messenger RNA transcripts for TGF-alpha, TGF-beta, platelet-derived growth factor A-chain, and insulin-like growth factor-1. The expression of these transcripts was determined by a novel method for RNA analysis in which low numbers of mouse macrophages were isolated from wound cylinders, their RNA was purified and reverse-transcribed, and the complementary DNA was amplified in a polymerase chain reaction primed with growth factor sequence-specific primers. This single-cell RNA phenotyping procedure is rapid and has the potential for quantification, and mRNA transcripts from a single cell or a few cells can be unambiguously demonstrated, with the simultaneous analysis of several mRNA species. Macrophages from wounds expressed TGF-alpha antigen, and wound fluids contained TGF-alpha. Elicited macrophages in culture also expressed TGF-alpha transcripts and polypeptide in a time-dependent manner after stimulation with modified low-density lipoproteins and lipopolysaccharide endotoxin, which are characteristic of the activators found in injured tissues.


Patterns of admission and factors associated with neonatal mortality among neonates admitted to the neonatal intensive care unit of University of Gondar Hospital, Northwest Ethiopia.
The neonatal period is a highly vulnerable time for an infant completing many of the physiologic adjustments required for life outside the uterus. As a result, there are high rates of morbidity and mortality. The three major causes of mortality in developing countries include prematurity, infection, and perinatal asphyxia. The aim of this study was to identify the patterns of neonatal admission and factors associated with mortality among neonates admitted at the Neonatal Intensive Care Unit (NICU) of University of Gondar Hospital. A retrospective cross-sectional study was conducted among all admitted neonates in the NICU of University of Gondar referral hospital from December 1, 2015 to August 31, 2016. Information was extracted retrospectively during admission from patient records and death certificates, using a pretested questionnaire. The data were entered and analyzed using SPSS version 20, and p-values <0.05 were considered statistically significant. A total of 769 neonates was included in the study. There were 448 (58.3%) male neonates, and 398 (51.8%) neonates were rural residents. More than two-thirds of the 587 deliveries (76.3%) were performed in tertiary hospitals. Neonatal morbidity included hypothermia 546 (71%), sepsis 522 (67.9%), prematurity 250 (34.9%), polycythemia 242 (31.5%), hypoglycemia 142 (18.5), meconium aspiration syndrome 113 (14.7%), and perinatal asphyxia 96 (12.5%). The overall mortality was 110 (14.3%; 95% confidence interval [CI]: 11.9-16.9) of which 69 (62.7%) deaths occurred in the first 24 hours of age. In the multivariate analysis, mortality was associated with perinatal asphyxia (adjusted odds ratio [AOR]: 5.97; 95% CI: 3.06-11.64), instrumental delivery (AOR: 2.99; 95% CI: 1.08-8.31), and early onset neonatal sepsis (AOR: 2.66; 95% CI: 1.62-6.11). Hypothermia, sepsis, and prematurity were the main reasons for NICU admission. Neonates often died within the first 24 hours of age. Implementing a better referral link and timely intervention could decrease neonatal mortality and morbidities in Gondar, Ethiopia.


A case-base sampling method for estimating recurrent event intensities.
Case-base sampling provides an alternative to risk set sampling based methods to estimate hazard regression models, in particular when absolute hazards are also of interest in addition to hazard ratios. The case-base sampling approach results in a likelihood expression of the logistic regression form, but instead of categorized time, such an expression is obtained through sampling of a discrete set of person-time coordinates from all follow-up data. In this paper, in the context of a time-dependent exposure such as vaccination, and a potentially recurrent adverse event outcome, we show that the resulting partial likelihood for the outcome event intensity has the asymptotic properties of a likelihood. We contrast this approach to self-matched case-base sampling, which involves only within-individual comparisons. The efficiency of the case-base methods is compared to that of standard methods through simulations, suggesting that the information loss due to sampling is minimal.


Correlates of the peridomestic abundance of Lutzomyia longipalpis (Diptera: Psychodidae) in Amazonian Brazil.
Abundance of the sandfly Lutzomyia longipalpis, the vector of Leishmania chagasi, was surveyed using CDC light-suction traps in fifteen villages and 180 homesteads on Marajó island, Pará State, Brazil. Flies were most abundant in cultivated areas, secondary growth and open woodland, away from savanna grassland and forest. Within homesteads, the abundance of flies in animal sheds was weakly associated with the number of hosts kept therein, and inversely related to the number elsewhere, both human and animal. Houses harboured more flies if dogs were present and if the house had: a roof of thatch rather than of tiles or tin; a thatched roof which had not been treated with insecticide; relatively more holes in walls and roof. The sex ratio of flies was more male-biased at higher densities. We weigh the importance of these variables as risk factors for Le. chagasi infection.


Transcriptome and proteome profiling to understanding the biology of high productivity CHO cells.
A combined transcriptome and proteome analysis was carried out to identify key genes and proteins differentially expressed in Chinese hamster ovary (CHO) cells producing high and low levels of dhfr-GFP fusion protein. Comparison of transcript levels was performed using a proprietary 15K CHO cDNA microarray chip, whereas proteomic analysis was performed using iTRAQ quantitative protein profiling technique. Microarray analysis revealed 77 differentially expressed genes, with 53 genes upregulated and 24 genes downregulated. Proteomic analysis gave 75 and 80 proteins for the midexponential and stationary phase, respectively. Although there was a general lack of correlation between mRNA levels and quantitated protein abundance, results from both datasets concurred on groups of proteins/genes based on functional categorization. A number of genes (20%) and proteins (45 and 23%) were involved in processes related to protein biosynthesis. We also identified three genes/proteins involved in chromatin modification. Enzymes responsible for opening up chromatin, Hmgn3 and Hmgb1, were upregulated whereas enzymes that condense chromatin, histone H1.2, were downregulated. Genes and proteins that promote cell growth (Igfbp4, Ptma, S100a6, and Lgals3) were downregulated, whereas those that deter cell growth (Ccng2, Gsg2, and S100a11) were upregulated. Other main groups of genes and proteins include carbohydrate metabolism, signal transduction, and transport. Our findings show that an integrated genomic and proteomics approach can be effectively utilized to monitor transcriptional and posttranscriptional events of mammalian cells in culture.


THE EVOLUTION OF HOST-PLANT USE AND SEQUESTRATION IN THE LEAF BEETLE GENUS PHRATORA (COLEOPTERA: CHRYSOMELIDAE).
Leaf beetles in the genus Phratora differ in host plant use and in the chemical composition of their larval defensive secretion. Most species specialize on either poplars or willows (family Salicaceae), but two species feed on birch (family Betulaceae). Phratora vitellinae utilizes salicylates from the host plant to produce its larval secretion, which contains salicylaldehyde, while other Phratora species produce an autogenous secretion. To reconstruct the evolutionary history of host plant use and the larval secretion chemistry in this genus, we sequenced 1383 base pairs of the mt cytochrome oxidase I gene for six European and one North American Phratora species and three outgroup taxa. Bootstrap values of the complete nucleotide sequence were 99-100% for six of eight nodes in the maximum parsimony tree. They were 71% and 77% for the two other nodes. The maximum parsimony tree and the maximum likelihood tree based on nucleotide sequence showed the same relationships as a maximum parsimony tree based on the amino acid sequence. Beetle phylogeny overlapped broadly with host plant taxonomy and chemistry, and it revealed historical constraints influencing host plant use. However, there was one host shift from the willow family (Salicaceae) to the birch family (Betulaceae). The use of host plant phenol glycosides for the larval defensive secretion evolved along the lineage that led to P. vitellinae. Phratora vitellinae feeds on the taxonomically widest range of host plants, which are characterized by moderate to high levels of salicylates. The results support the hypothesis that the use of salicylates for the larval secretion evolved twice independently in chrysomeline leaf beetles.


Surface electrical stimulation perturbation context determines the presence of error reduction in swallowing hyolaryngeal kinematics.
Error-based learning (EBL) involves gradually reducing movement errors caused by a perturbation. When the perturbation has been unexpectedly removed, exaggerated movements occur in the opposite direction of a perturbation effect, known as aftereffects. Our goal was to determine whether the perturbation type impacts error reduction or aftereffects in swallowing hyolaryngeal kinematics. We perturbed peak hyolaryngeal elevation during swallowing in 16 healthy adults with surface electrical stimulation (SES) in 2 different ways during videofluoroscopy: intermittent SES (I-SES) was applied only during swallowing, and continuous SES (C-SES) was applied during swallowing and during interswallow intervals. In C-SES and I-SES, the onset and offset of the perturbation were unmasked. Only the C-SES perturbation caused error reduction (gradually increasing peak elevation). Aftereffects were absent in both perturbations, unlike findings from our previous study with masked perturbation. Furthermore, the duration of laryngeal vestibule closure (dLVC) increased during the I-SES perturbation but was unchanged during C-SES perturbation. EBL of swallowing airway protection events was strongly influenced by the context of the perturbation. These findings also elucidate how the relationship among critical swallowing airway protection events (hyoid peak, laryngeal peak, and dLVC) can be modified during EBL.


[Role of Flow Cytometry in the Diagnosis of Chronic Myeloid Leukemia].
To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance. The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups. The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI. The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.


Guidelines for clinical trials in melasma. Pigmentation Disorders Academy.
There have been very few well-conducted trials in melasma and this makes the process of comparing treatment outcome between trials difficult. The Pigmentary Disorders Academy has examined the issues relating to clinical trials on melasma, and has proposed recommendations on how they should be conducted. This covers all aspects including correct diagnosis of the condition, evaluation of efficacy and safety outcome, and overall clinical trial design. It is anticipated that the establishment of accepted guidelines on the conduct of clinical trials in melasma will greatly assist the dermatological community.


Application of real-time PCR to monitor population dynamics of defined mixed cultures of moderate thermophiles involved in bioleaching of chalcopyrite.
To compare oxidative dissolution rates of chalcopyrite by different consortia of moderately thermophilic acidophiles, various defined mixed cultures of three bacteria Acidithiobacillus caldus s2, Leptospirillum ferriphilum YSK, and Sulfobacillus sp. LN and one archaeon Ferroplasma thermophilum L1 were studied in batch shake flask cultures incubated at 45 degrees C. Chalcopyrite dissolution was determined by measuring variations of soluble copper, ferric iron, and pH. Microbial population dynamics involved in bioleaching process were monitored using real-time quantitative polymerase chain reaction (PCR) technology. The complex consortia containing both chemoautotrophic (L. ferriphilum and At. caldus) and chemomixotrophic (Sulfobacillus LN and F. thermophilum) moderate thermophiles were found to be the most efficient in all of those tested. Mutualistic interactions between physiologically distinct moderately thermophilic acidophiles, involving transformations of iron and sulfur and transfer of organic compound, were considered to play a critical role in promoting chalcopyrite dissolution. The real-time PCR assay was reliable to analyze population dynamics of moderate thermophiles in bioleaching systems, and the analysis results were consistent with physiological characteristics of these strains.


Treatment outcomes and associated factors among children with severe acute malnutrition at Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia: a retrospective cohort study.
Ethiopia is one of the countries with the highest under-five child mortality rates, with malnutrition remaining the major cause of death. Overall, 10% of children in Ethiopia are wasted, and 3% are severely wasted. To assess the treatment outcomes and associated factors among children with severe acute malnutrition (SAM) at Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia, data of 162 under-five children admitted from January to December, 2020, at Hiwot Fana Specialized University hospital were collected retrospectively from 1 January to 20 February 2021. Pre-tested structured questionnaire was used to extract data from medical records. The data was entered into Statistical Package for the Social Sciences version 21 for analysis. A p-value <0.05 was considered statistically significant. In this study, 162 participants were included and 54% were males. The majority (80.2%) of children were newly admitted and 49.7% had less than 7 days of hospital stay, 70.99% recovered from malnutrition, and 42.6% had marasmus. Amoxicillin and gentamycin combination (47.5%) was the most commonly prescribed intravenous antibiotics. Having diarrhoea (AOR = 22, 95% CI: 2.86-169.46), presence of comorbidities such as malaria (AOR = 103.29, 95% CI: 7.42-1437.74) and human immunodeficiency virus (HIV) (AOR = 42.72, 95% CI: 4.47-408.23) were statistically associated with poor recovery from severe malnutrition. More than 70% of children with SAM had good treatment outcomes. Child vaccination history, length of hospital stay, admission weight for height, and presence of comorbidities such as diarrhoea, pneumonia, measles, HIV, malaria, and tuberculosis were factors associated with bad malnutrition and treatment outcomes.


Effect of head-centered and body-centered hemispace in unilateral neglect.
The aim of this study was to evaluate the effects of head-centered and body-centered hemispace on a line bisection task in patients with left unilateral neglect. Five patients with left unilateral neglect were given a line bisection task under four different conditions. The results clearly demonstrate that both head-centered and body-centered hemispace had a statistically significant effect on the line bisection task. The results are discussed with respect to a reference frame of space and the validity of dividing unilateral neglect into two components (i.e., spatial neglect and object neglect) is proposed.


CD of proline-rich polypeptides: application to the study of the repetitive domain of maize glutelin-2.
An overview of CD of proline-rich peptides is reported. First, structural characteristics, theoretical CD studies, and the biological relevance of polyproline II structure in such peptides are discussed. Second, a CD study of peptides belonging to the repetitive domain of maize glutelin-2, H-(Val-His-Leu-Pro-Pro-Pro)n-OH (n = 3, 5, 8), is described. This series of peptides displayed the CD features of polyproline II structure in water (5 degrees C, pH 5). Moreover, it was shown that the addition of increasing amounts of the polyanionic molecule heparin forced a displacement of the conformational equilibrium of those peptides toward higher proportions of the polyproline II structure. In contrast, when the temperature is raised such a structure gradually disappears, leading to more disordered conformations.


Release of neurohypophysial hormones in vitro.
1. The rate of release of neurohypophysial hormones in vitro, using isolated, halved neural lobes of the rat in an incubation medium containing excess K(+) and Ca(2+), was measured. The highest average rate of release was observed between 10 and 20 min after commencement of incubation.2. Incubation of isolated, halved rat neural lobes in the presence of acetylcholine, with or without eserine, did not stimulate hormone release. When complete isolated hypothalamo-neurohypophysial systems were incubated in a suspension medium containing 10(-7) mg/ml. acetylcholine a significant increase in the release of oxytocin occurred (P < 0.01); the increase in vasopressin release was less pronounced (P < 0.05).3. Uptake of O(2) by the isolated, halved neural lobes and the hypothalamo-neurohypophysial systems continued for 2-3 hr, i.e. in excess of the experimental incubation time.4. During the first 40 min of incubation the control halved neural lobes increased in weight; the neural lobes incubated in buffer containing high potassium and calcium showed no increase in weight.5. Neural lobes incubated in buffer containing excess K(+) and Ca(2+) contained about 3 times as much potassium as controls. The sodium content was not affected significantly.6. Factors involved in the process of neurohypophysial hormone release are discussed.


Total Syntheses of Resin Glycosides Murucoidins IV and V.
Murucoidins IV and V, two bioactive resin glycosides with complex yet similar structures isolated from the morning glory family, were synthesized in a convergent manner. All of the glycosylations in these syntheses including the key [3 + 2] coupling were achieved by our recently developed interrupted Pummerer reaction mediated (IPRm) glycosylations. The broad functional group compatibility of IPRm glycosylation allowed us to employ a latent-active concept and a single-pot transient protection-glycosylation-deprotection strategy which significantly improved the global synthetic efficiency.


Titanium dioxide visible light photocatalysis: surface association enables photocatalysis with visible light irradiation.
Titanium dioxide (TiO2) is a widely employed and inexpensive photocatalyst, but its use in organic synthesis has been limited by the short-wavelength ultraviolet irradiation typically used. We have discovered that TiO2 particles efficiently mediate photocatalytic radical cation Diels-Alder cycloadditions using a simple visible light source, enabled by the formation of a visible light absorbing complex of the substrate on the semiconductor surface.


Quantification of amphetamine-induced changes in [11C]raclopride binding with continuous infusion.
Positron emission tomography and single-photon emission computer tomography receptor-binding ligands can be used to measure changes in neurotransmitter levels. In particular, amphetamine-induced dopamine release has been assessed with [11C]raclopride by paired bolus injections and with [123I]iodobenzamide by using a single bolus plus infusion (B/I) study. Here, we measured the change in [11C]raclopride-specific binding in rhesus monkeys after i.v. administration of 0.4 mg/kg amphetamine by using both the bolus and B/I paradigms. Paired bolus studies (control and postamphetamine) were analyzed using compartment modeling and graphical analysis with a new plasma metabolite model to measure the total distribution volume (VT). Specific binding, calculated with three measures linearly proportional to the binding potential, demonstrated a 22-42% reduction in the postamphetamine study. VT values from B/I studies were determined by the tissue-to-plasma ratio at equilibrium, in addition to the bolus methods. There was good agreement between the control VT values between bolus and B/I studies. The amphetamine-induced change in specific binding in B/I studies was 19 +/- 16%, measured directly from tissue radioactivity levels. This study demonstrates that stimulus-induced changes in specific binding can be measured with a single [11C]raclopride study using the B/I method.


Effects of centrally injected GLP-1 in various experimental models of gastric mucosal damage.
Glucagon-like peptide-1 (GLP-1) is accepted to be a peptide involved in the central regulation of gastrointestinal function, but its potential gastroprotective effect is not clear. The aim of this study was to investigate whether intracerebroventricularly injected GLP-1 has protective effects on gastric mucosal lesions induced by several models, and if yes, whether these effects are due to the gastric antisecretory effect of the peptide. GLP-1 which was injected in three different doses (1, 10, 100 ng/10 microl; i.c.v.) to conscious rats prevented the mucosal lesions induced by reserpine and ethanol, but did not prevent the gastric mucosal lesions induced by pyloric ligation. In addition, 1 ng/10 microl dose of centrally injected GLP-1 inhibited gastric acid secretion in pylorus-ligated rats. As a result, we conclude that intracerebroventricularly injected GLP-1 may play a role in the prevention of gastric mucosal lesions induced by certain experimental models and this gastroprotective effect may be independent from its antisecretory effect.


Antiemetic and Myeloprotective Effects of Rhus verniciflua Stoke in a Cisplatin-Induced Rat Model.
Rhus verniciflua Stoke has been commonly used in traditional medicine to treat gastrointestinal (GI) dysfunction diseases. In order to investigate pharmacological properties of Rhus verniciflua Stoke water extract (RVX) on cisplatin-induced amnesia, RVX (0, 25, 50, or 100 mg/kg) was orally administrated for five consecutive days after a single intraperitoneal injection of cisplatin (6 mg/kg) to SD rat. Cisplatin injection significantly increased the kaolin intake (emesis) but reduced the normal diet intake (anorexia) whereas the RVX treatment significantly improved these abnormal diet behaviors at both the acute and delayed phase. The serotonin concentration and the related gene expressions (5-HT3 receptors and SERT) in small intestine tissue were abnormally altered by cisplatin injection, which were significantly attenuated by the RVX treatment. Histological findings of gastrointestinal tracts, as well as the proteins level of proinflammatory cytokines (TNF-α, IL-6, and IL-1β), revealed the beneficial effect of RVX on cisplatin-induced gastrointestinal inflammation. In addition, RVX significantly improved cisplatin-induced myelosuppression, as evidenced by the observation of leukopenia and by histological examinations in bone marrow. Our findings collectively indicated Rhus verniciflua Stoke improved the resistance of rats to chemotherapy-related adverse effects in the gastrointestinal track and bone marrow.


Sex, Race, and Socioeconomic Disparities in Patients With Aortic Stenosis (from a Nationwide Inpatient Sample).
Aortic stenosis (AS) is the third most prevalent cardiovascular disease following hypertension and coronary artery disease. The primary objective of this cross-sectional study is to examine gender, racial, and socioeconomic disparities in AS-related health care utilization in patients aged ≥50 years using data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. AS was identified among inpatient discharges with International Classification of Diseases, Ninth Revision, Clinical Modification, code 424.1. Using stratum-specific weighted totals, means, proportions, and regression models, we examined time trends and disparities for inhospital AS prevalence according to gender, race, and income over the 2002 to 2012 period, predictors of AS (gender, race, income, age, health insurance, co-morbidities, and hospital-level characteristics), and AS's role as a predictor of inhospital death, length of stay, and total charges. Inhospital AS prevalence increased from 2.10% in 2002 to 2.37% in 2012, with similar trends observed within gender, race, and income strata. Women were less likely to have AS compared with men (adjusted odds ratio [ORadj] 0.84; 95% confidence interval [CI] 0.83 to 0.86). Blacks (ORadj 0.68; 95% CI 0.66 to 0.71), Hispanics (ORadj 0.79; 95% CI 0.76 to 0.84), and Asians/Pacific Islanders (ORadj 0.68; 95% CI 0.64 to 0.74) were less likely than whites to have AS diagnosis that was directly associated with income. AS was inversely related to inhospital death but positively linked to total charges overall and longer hospital stays among men, whites, and middle-income patients. However, shorter stays with AS were observed among blacks. In conclusion, among older inpatients, AS prevalence was ∼2% and was higher among males, whites, and higher income groups. Although inhospital death was lower and total charges were higher in AS, length of stay's association with AS varied by gender, race, and income.


Inhibition of complement activation by a secreted Staphylococcus aureus protein.
Staphylococcus aureus can cause a variety of acute and chronic diseases. The ability of S. aureus to cause persistent infections has been linked to its ability to evade or inactivate host immune responses. We have identified a secreted 19-kDa protein produced by S. aureus that binds to the complement protein C3. N-terminal sequencing of this protein identified it as the extracellular fibrinogen-binding protein (Efb). In this study, we demonstrate that Efb can bind to the alpha -chain of C3 and inhibit both the classical and alternative pathways of complement activation. In addition, we show that Efb can inhibit complement-mediated opsonophagocytosis in a dose-dependent manner and that Efb inhibits complement activity by blocking deposition of C3 or by preventing further complement activation beyond C3b. These data suggest that Efb is a virulence factor involved in facilitating persistent S. aureus infections by interfering with complement activity in vivo.


Removal of sediment and bacteria from water using green chemistry.
Although nearly all newly derived water purification methods have improved the water quality in developing countries, few have been accepted and maintained for long-term use. Field studies indicate that the most beneficial methods use indigenous resources, as they are both accessible and accepted by communities they help. In an effort to implement a material that will meet community needs, two fractions of mucilage gum were extracted from the Opuntia ficus-indica cactus and tested as flocculation agents against sediment and bacterial contamination. As diatomic ions are known to affect both mucilage and promote cell aggregation, CaCl(2) was studied in conjunction and compared with mucilage as a bacteria removal method. To evaluate performance, ion-rich waters that mimic natural water bodies were prepared. Column tests containing suspensions of the sediment kaolin exhibited particle flocculation and settling rates up to 13.2 cm/min with mucilage versus control settling rates of 0.5 cm/min. Bacillus cereus tests displayed flocculation and improved settling times with mucilage concentrations lower than 5 ppm and removal rates between 97 and 98% were observed for high bacteria concentration tests (>10(8) cells/ml). This natural material not only displays water purification abilities, but it is also affordable, renewable and readily available.


Hemodynamic, blood volume, and oxygen transport responses to albumin and hydroxyethyl starch infusions in critically ill postoperative patients.
Hemodynamic, plasma volume, and oxygen transport effects were measured after administration of 500 ml of 5% albumin or 6% hydroxyethyl starch (HES) in hypovolemic postoperative patients using a prospectively randomized crossover design. Both agents produced marked and significant improvement in plasma volume and flow as well as small transient increases in arterial and venous pressures, urine output, colloidal osmotic pressure (COP), and oxygen transport. The authors conclude that HES is a safe, inexpensive, effective plasma expander that has hemodynamic effects similar to those of other colloids. It was apparent from these and other studies that clinically stable postoperative patients may have appreciable blood volume deficits. Routine vital signs correlated poorly with the preinfusion control hemodynamic values or the changes in blood volume status after volume loading. Normal cardiac output, central venous pressure (CVP), and pulmonary arterial wedge pressure (WP) values are commonly seen in critically ill postoperative patients who, nevertheless, may be hypovolemic. Measurement of changes in these variables after a fluid challenge is a useful way to assess plasma volume status.


Positioning of the NOR-bearing chromosomes in relation to nucleoli in daughter cells after mitosis.
It is known that chromosomes occupy non-random positions in the cell nucleus. However, it is not clear to what extent their nuclear positions, together with their neighborhood, are conserved in daughter cells. To address specific aspects of this problem, we used the model of the chromosomes carrying ribosomal genes that are organized in clusters termed Nucleolus Organizer Regions (NORs). We compared the association of chosen NOR-bearing chromosomes (NOR-chromosomes) with nucleoli, as well as the numbers of nucleoli, in the pairs of daughter cells, and established how frequently the daughter cells had equal numbers of the homologs of certain NOR-chromosomes associated with individual nucleoli. The daughter cells typically had different numbers of nucleoli. At the same time, using immuno-FISH with probes for chromosomes 14 and 15 in HeLa cells, we found that the cell pairs with identical combinations appeared significantly more frequently than predicted by the random model. Thus, although the total number of chromosomes associated with nucleoli is variable, our data indicate that the position of the NOR-bearing chromosomes in relation to nucleoli is partly conserved through mitosis.


Molecular dynamics simulation of polyethylene on single wall carbon nanotube.
Molecular dynamics simulations are carried out on the isothermal crystallization process of single polyethylene chains with different chain lengths on the single wall carbon nanotube. This process is summarized as two steps, i.e., adsorption and orientation, and the bond-orientational order parameter is used to show the details of this process. The results show that the attractive van der Waals interactions control the adsorption and orientation of polyethylene on single wall carbon nanotube, and as the chain length increases, more microstructures appear in the last ordered structure. The stems of the ordered structure align parallel to the single wall carbon nanotube axis.


I am an Educator: Investigating Professional Identity Formation using Social Cognitive Career Theory.
PhenomenonClinician-educators (CE) are physicians who fill a unique role within academic medicine, as they are responsible both for patient care and for training future physicians via teaching, curricular design, and creation of educational scholarship. Development of a strong professional identity as an educator leads to greater career satisfaction and a higher likelihood of staying in academic medicine. However, little is known about how this identity develops, especially in the training environment where there are competing pressures to develop as a clinician and researcher. This study aimed to explore professional identity formation in residents and fellows interested in becoming educators. Approach: We used a longitudinal, qualitative approach to investigate professional identity formation in residents and fellows participating in the Clinician-Educator Training Pathway. The longitudinal nature allowed us to temporally explore which aspects of the program and experiences acted as barriers or facilitators of professional identity formation as a CE. Our study used the social cognitive career theory (SCCT) Career Choice Model, which considers contextual influences in addition to the three variables of self-efficacy beliefs, outcome expectations, and goals. Findings: We found that participants shared a common goal of building self-efficacy as an educator. Participants took actions to engage more deliberately in formal and informal teaching and acting as an educator by giving learner feedback, developing curricula, and consuming and conducting educational research, all of which increased self-efficacy as educators. At the beginning of the program, participants were unclear of the roles and trajectories followed to become CEs. Engaging with a community of CEs clarified pathways and presented role models that could be seen as possible selves. This study also elucidated contextual influences relating to personal factors, career opportunities, and potential for advancement that mediated the goals and actions taken by participants to become educators. Insights: This study demonstrates that the SCCT Career Choice Model provides an excellent framework for understanding professional identity formation in future educators. Our participants built self-efficacy, formed outcome expectations, and set goals and took specific actions toward the goal of becoming an educator. Participants tested the various role model attributes as possible selves to see how those would be effective in their own career. Reflection on expectations, career goals, and self-efficacy as a clinician and an educator can assist in identity formation as a CE and can assist those designing CE training programs to better support identity formation in their participants.


A recombination based method to rapidly assess specificity of two-hybrid clones in yeast.
The yeast two-hybrid system is frequently used to identify protein-protein interactions. Confirming the specificity of candidate clones requires separation and isolation of yeast plasmids, propagation in bacteria and testing combinations of DNA-binding and activation domain hybrids in yeast. In order to simplify this procedure, we developed a rapid method based on PCR amplification of library insert DNAs and in vivo cloning into the activation domain hybrid vector. Reporter gene activity is assayed in parallel for combinations with different DNA-binding domain hybrids. Further characterization of inserts does not require plasmid isolation and intermediate hosts.


Minimally Invasive Parafascicular Surgery (MIPS) for Spontaneous Intracerebral Hemorrhage Compared to Medical Management: A Case Series Comparison for a Single Institution.
We compared the safety and effectiveness of minimally invasive parafascicular surgery (MIPS) as a frontline treatment for spontaneous supratentorial ICH to medical management. Patients. The sample consisted of 17 patients who underwent MIPS from January 2014 to December 2016 and a comparison group of 23 patients who were medically managed from June 2012 to December 2013. All had an International Classification of Disease (ICD) diagnosis of 431 and were treated at Grady Memorial Hospital, an urban, public, safety-net hospital. The primary endpoint was risk of inpatient mortality. Secondary endpoints were rates of inpatient infection and favorable discharge status, defined as discharge to home or rehabilitation facility. Demographics and pre- and postclinical outcomes were compared using t-tests, the Mann-Whitney test, and chi-squared tests for continuous, ordinal and categorical measures, respectively. Cox proportional hazard models were used to estimate the time to inpatient death. Logistic regression analyses were used to determine treatment effects on secondary outcomes. We also conducted exploratory subgroup analyses which compared MIPS to two medical management subgroups: those who had surgery during their hospitalization and those that did not. Two patients (12%) died in the MIPS group compared to three (12%) in the medical management group. MIPS did not increase the risk of inpatient mortality relative to medical management. Rates of inpatient infection did not differ significantly between the two groups; eight MIPS patients (47%) and 13 medically managed patients (50%) contracted infections. MIPS significantly increased the likelihood of favorable discharge status (odds ratio (OR) 1.77; 95% CI, 1.12-21.9) compared to medical management. No outcome measures were significantly different between MIPS and the medical management subgroup without surgery, while rates of favorable discharge were higher among the MIPS patients compared to the medical management group with surgery. These data suggest that MIPS, as a frontline treatment for spontaneous ICH, versus medical management for spontaneous ICH warrants further investigation.


Diagnosis of porcine proliferative enteropathy: detection of Lawsonia intracellularis by pathological examinations, polymerase chain reaction and cell culture inoculation.
A total of 21 pigs aged 7-17 weeks with clinical symptoms suggestive for Porcine Proliferative Enteropathy were examined for Lawsonia intracellularis by analysing the following parameters: (i) intestinal gross and histological lesions, (ii) presence of comma-shaped bacteria in enterocytes by Warthin-Starry and a modified Ziehl-Neelsen stain, (iii) PCR amplification of L. intracellularis DNA from intestinal mucosa by using two oligonucleotide primer pairs targeting a 255-bp DNA fragment of the 16S rDNA-gene and a 319-bp DNA fragment of the L. intracellularis chromosome. Specificity of PCR reactions was confirmed by using DNA extracted from the L. intracellularis reference strain N343 (ATCC 55672) as well as by DNA sequence comparisons of PCR amplification products with data bank entries. Intestinal gross lesion indicative for PPE were observed in 20 pigs (95.2%). For all 21 pigs, the L. intracellularis aetiology was confirmed by histological as well as bacterioscopical examinations. Specific PCR amplification products were obtained from 20 pigs (95.2%). Taking PCR positivity as the definite criterion, L. intracellularis was diagnosed in 20 pigs from 11 herds in seven Swiss cantons (Argovia, Berne, Fribourg, Grisons, Lucerne, Schwyz, Thurgovia). To grow L. intracellularisin vitro, the cell culture method of Lawson et al. (J. Clin. Microbiol. 1993: 31, 1136-1142) was adopted. Inocula prepared from heavily infected fresh and frozen ileal mucosa of 15 pigs were cultured in rat enterocytic IEC-18 cells (ATCC CRL 1589). Six cell culture passages of 10 days each were completed. The reference strain N343 was examined for cultivability, accordingly. Except for occasional specific PCR amplifications from cell cultures up to the second passage, any indications for growth of L. intracellularis in IEC-18 cells were not found.


Dynamic hydrodistention classification of the ureter and the double hit method to correct vesicoureteral reflux.
The objective of this monograph is to familiarize the reader with dynamic hydrodistention classification of the ureter and Hydrodistention Implantation Technique (HIT) methodology for the endoscopic correction of vesicoureteral reflux (VUR). The indications, current success rates, complications, and potential future applications of these methods are reviewed. Hydrodistention (HD) of the ureteral orifice and distal ureter permits visualization of the intraureteral submucosal injection site and assessment of the degree of ureteral coaptation. We have designated 4 levels of HD. HO denotes absence of ureteral dilation, H1 indicates dilation of the ureteral orifice only. H2 allows visualization of the intramural ureter, and H3 allows visualization of the extramural ureter. The Double HIT method is a systematic technique that utilizes HD to both classify the ureter and gauge the degree of ureteral coaptation secondary to bulking during endoscopic injection. The needle is inserted at the mid ureteral tunnel at the 6 o'clock position. The first injection coapts the detrusor tunnel (until H1 or H0 is achieved), while a second implant within the most distal intramural tunnel leads to complete coaptation of the ureteral orifice (H0). HD grade correlated significantly with VUR grade. Normal ureters rarely hydrodistended. While non-refluxing contralateral ureters demonstrated low HD grades, all contralateral ureters that subsequently developed VUR showed H2 or H3. The HIT method has not only been employed for primary VUR (90% cure), but also for repeat endoscopic injections (90%), VUR associated with paraureteral diverticula (81%), complex cases such as post-reimplantation (88%), neurogenic bladders (78%), duplication anomalies (80%), and in adults (88%). Furthermore, injection of contralateral VUR-negative but hydrodistending ureters may be treated to prevent new contralateral VUR. While decreasing success was seen with increasing VUR grade with the STING method, superior success rates have been realized with the HIT method. The dynamic hydrodistention classification reflects the competency of the ureterovesical junction. The HIT and Double HIT methods achieve superior cure rates and are likely to become the method of choice for the treatment of primary as well as complex cases of VUR.


Human-centered design of a personal health record system for metabolic syndrome management based on the ISO 9241-210:2010 standard.
Previous studies have demonstrated the effectiveness of information and communication technologies to support healthy lifestyle interventions. In particular, personal health record systems (PHR-Ss) empower self-care, essential to support lifestyle changes. Approaches such as the user-centered design (UCD), which is already a standard within the software industry (ISO 9241-210:2010), provide specifications and guidelines to guarantee user acceptance and quality of eHealth systems. However, no single PHR-S for metabolic syndrome (MS) developed following the recommendations of the ISO 9241-210:2010 specification has been found in the literature. The aim of this study was to describe the development of a PHR-S for the management of MS according to the principles and recommendations of the ISO 9241-210 standard. The proposed PHR-S was developed using a formal software development process which, in addition to the traditional activities of any software process, included the principles and recommendations of the ISO 9241-210 standard. To gather user information, a survey sample of 1,187 individuals, eight interviews, and a focus group with seven people were performed. Throughout five iterations, three prototypes were built. Potential users of each system evaluated each prototype. The quality attributes of efficiency, effectiveness, and user satisfaction were assessed using metrics defined in the ISO/IEC 25022 standard. The following results were obtained: 1) a technology profile from 1,187 individuals at risk for MS from the city of Popayan, Colombia, identifying that 75.2% of the people use the Internet and 51% had a smartphone; 2) a PHR-S to manage MS developed (the PHR-S has the following five main functionalities: record the five MS risk factors, share these measures with health care professionals, and three educational modules on nutrition, stress management, and a physical activity); and 3) usability tests on each prototype obtaining the following results: 100% effectiveness, 100% efficiency, and 84.2 points in the system usability scale. The software development methodology used was based on the ISO 9241-210 standard, which allowed the development team to maintain a focus on user's needs and requirements throughout the project, which resulted in an increased satisfaction and acceptance of the system. Additionally, the establishment of a multidisciplinary team allowed the application of considerations not only from the disciplines of software engineering and health sciences but also from other disciplines such as graphical design and media communication. Finally, usability testing allowed the observation of flaws in the designs, which helped to improve the solution.


Kinetics of intestinal lamina propria mast cells, globule leucocytes, intraepithelial lymphocytes, goblet cells and eosinophils in murine strongyloidiasis.
The changes in numbers of 6 cell populations in the intestine of mice at various intervals after primary and challenge infections with Strongyloides ratti have been quantified. The number of lamina propria mast cells increased 8 days after primary infection and reached a peak at 12 days. After secondary infection, there was a transient fall in mast cell numbers followed by a slow increase. Globule leucocytes showed a similar trend early in the primary infection and had reached normal levels after 28 days. After challenge infection, there was an early and rapid increase in their numbers. Granular intraepithelial lymphocytes did not alter significantly during the first 14 days, but were significantly greater 28 days after primary infection; they did not vary significantly after challenge infection. However, numbers of non-granular intraepithelial lymphocytes increased 10 days after infection, were elevated prior to the secondary infection at 28 days, then declined in numbers nearly 2 weeks after challenge infection. Goblet cells increased significantly 12 days after primary infection then declined rapidly. After challenge infection, there was an accelerated increase in numbers. Eosinophil numbers increased 4 days after infection, reached a peak at 12 days and then declined. After challenge infection, there was an augmented and accelerated increase in eosinophil numbers followed by rapid decline. The role of the various cells types in host defences against worms or in containment of the inflammatory responses evoked by these parasites are discussed.


The cell's nucleolus: an emerging target for chemotherapeutic intervention.
The transient nucleolus plays a central role in the up-regulated synthesis of ribosomal RNA (rRNA) to sustain ribosome biogenesis, a hallmark of aberrant cell growth. This function, in conjunction with its unique pathohistological features in malignant cells and its ability to mediate apoptosis, renders this sub-nuclear structure a potential target for chemotherapeutic agents. In this Minireview, structurally and functionally diverse small molecules are discussed that have been reported to either interact with the nucleolus directly or perturb its function indirectly by acting on its dynamic components. These molecules include all major classes of nucleic-acid-targeted agents, antimetabolites, kinase inhibitors, anti-inflammatory drugs, natural product antibiotics, oligopeptides, as well as nanoparticles. Together, these molecules are invaluable probes of structure and function of the nucleolus. They also provide a unique opportunity to develop novel strategies for more selective and therefore better-tolerated chemotherapeutic intervention. In this regard, inhibition of RNA polymerase-I-mediated rRNA synthesis appears to be a promising mechanism for killing cancer cells. The recent development of molecules targeted at G-quadruplex-forming rRNA gene sequences, which are currently undergoing clinical trials, seems to attest to the success of this approach.


The effect of PUVA treatment on acid hydrolases in human polymorphonuclear leukocytes.
The activity of intracellular acid hydrolases in polymorphonuclear leukocytes (PMNL) from psoriatic patients and normal control subjects was determined. No significant differences between healthy and psoriatic individuals were detected, but a slight decrease in acid hydrolase activity was found in PMNL of psoriasis patients during PUVA therapy. PUVA treatment of PMNL in vitro at intensities that may be achieved in situ in the epidermis led to intracellular inactivation of acid hydrolases, which was not due to secretion of the enzymes or cell damage. The decrease in PMNL hydrolase activity appeared to be evoked by PUVA-generated reactive oxygen species because reduced glutathione prevented this decrease. The activity of free extracellular acid hydrolases was not affected by PUVA, and the superoxide production of PUVA-treated PMNL was increased. These results suggest that intracellular inactivation of acid hydrolases and possibly other lysosomal enzymes in PMNL or monocytes infiltrating the epidermis may contribute to the antipsoriatic activity of PUVA therapy.


Transcatheter therapies for tricuspid regurgitation: coaptation augmentation devices.
Advancements in transcatheter technology has increased the number of therapeutic options for patients with tricuspid regurgitation. One category of repair devices attempts to augment leaflet coaptation by either leaflet plication or by functioning as a space occupying device. These include the MitraClip (Abbott, Santa Clara, CA, USA), PASCAL (Edwards Lifesciences, Irvine, CA, USA) and FORMA (Edwards Lifesciences, Irvine, CA, USA) devices. All three have been successfully implanted with promising short-term echocardiographic and clinical outcomes. Improvements in patient selection, device design and procedural technique will lead to more effective tricuspid regurgitation reduction. Further research to assess efficacy, safety and durability of these devices is needed, along with determination of long-term clinical outcomes.