Condom distribution: a cost-utility analysis.
To explore the cost-effectiveness of a condom distribution programme. We conducted a cost-utility analysis of a social marketing campaign in which over 33 million condoms were made freely available throughout Louisiana. Surveys among 275,000 African Americans showed that condom use increased by 30%. Based on the estimated cost of the intervention and costs of HIV/AIDS-associated medical treatment, we estimated the quality-adjusted life years (QALYs) saved, and number of HIV infections averted by the programme. The programme was estimated to prevent 170 HIV infections and save 1909 QALYs. Over $33 million in medical care costs were estimated to be averted, resulting in cost savings. Sensitivity analyses showed that these results were quite stable over a range of estimates for the main parameters. Condom increases as small as 2.7% were still cost-saving. Condom distribution is a community-level HIV prevention intervention that has the potential to reach large segments of the general population, thereby averting significant numbers of HIV infections and associated medical costs. The intervention is easy to scale up to large populations or down to small populations. The financial and health benefits of condom social marketing support making it a routine component of HIV prevention services nationally.


Healthcare professionals and the ethics of healthcare marketing.
The article explores marketing ethics considerations in the application of marketing to healthcare. While we realize that acceptance of healthcare marketing by all stakeholders is important for successful marketing, we emphasize its level of acceptance by healthcare professionals. The high levels of resistance to advertising and other forms of healthcare marketing by healthcare professionals has been largely based on the grounds that the practices are unethical. The nature of the resistance thus invites this exploration of healthcare marketing (and the marketing concept), marketing ethics, and the acceptance (rejection) by healthcare professionals of healthcare marketing.


The solvation of NaCl in model water with different hydrogen bond strength.
Based on hybrid water models, we design a series of solvent environments with different hydrogen bond strength and study the solvation of NaCl in them. The microstructures and dynamical behaviors of solvents and ion solutes are presented in detail to trace the correlations between the hydrogen bond strength of water and the solvation mechanism of the ions. In the process of the solvation of NaCl, the balance of the competition between breaking original solvent structures and formation of hydration shells around ions is sensitive to the hydrogen bonding ability of water. The results indicate that NaCl is most ideally dissolved in natural water with the strongest hydration effects around both cations and anions. In solvents with both reduced and enhanced hydrogen bond strength, the ions are more inclined to be in contact or aggregate into clusters of different sizes. These phenomena show that appropriate hydrogen bond strength is crucial for water's natural dissolving capacity.


Effect of 4-aminopyrazolo[3,4-d]pyrimidine on the catabolism of high-density lipoprotein apolipoprotein A-I in the rat.
The in vivo turnover and sites of catabolism of O-(4-diazo-3-[125I]iodobenzoyl)sucrose-labelled rat high-density lipoprotein (HDL) apolipoprotein A-I were studied in rats treated for 3 days with 4-aminopyrazolo-[3,4-d]pyrimidine (4APP). It was found that 4APP treatment decreases the serum cholesterol concentration to 6 mg/dl and stimulates the serum decay of labelled HDL. The latter effect could be attributed to an increased catabolism of radioactive HDL apolipoprotein A-I by the liver. When the serum cholesterol concentration was raised to physiological levels by a bolus injection of unlabelled rat HDL, at the time of administration of the labelled HDL, the serum decays and the tissue uptakes of apolipoprotein A-I labelled HDL were identical in 4APP-treated rats and control animals. When a bolus injection of unlabelled human low-density lipoprotein (LDL) was administered to 4APP-treated rats, the serum decay and tissue uptake of apolipoprotein A-I labelled HDL remained rapid. The recovery of radioactivity in the adrenal glands was increased almost 10 fold by 4APP treatment, a phenomenon which was reversed by a bolus injection of unlabelled HDL, but not by injection of unlabelled LDL. It is concluded that treatment of rats with 4APP does not affect the rate of catabolism of rat HDL apolipoprotein A-I, when the serum HDL concentration in the treated animals is restored to physiological levels.


Participating in a new group and the identification processes: The quest for a positive social identity.
Immigrants experience identity shifts; they can identify with the new cultural group and, sometimes, identify less with their group of origin. Previous research suggests that participation in the new cultural group predicts these two identity shifts. However, these studies have exclusively used correlational methodologies. Furthermore, previous research ignored that when a group is negatively valued, individuals may not identify with it, even after participating in it, to preserve a positive social identity. This article tests with an experimental methodology whether participation recreated the identity shifts previously identified (greater identification with the new group and lower identification with the group of origin when perceiving dissimilarity). Furthermore, it tested how a group's value impacted these identity shifts following participation. Immigrants in Quebec (N = 184) either participated in Quebec's culture (watched hockey) or did not (watched basketball). Quebec's value was manipulated by changing whether Quebec won, tied, or lost the game. Compared to watching basketball, watching Quebec's team win or tie showed the hypothesized identity shifts, illustrating the importance of the new group's value when participating.


Outside the pattern: Evolution of the genital asymmetry in Saicinae (Hemiptera: Heteroptera: Reduviidae).
Despite genital structures in insects being consistently important as systematic and taxonomy evidence, within assassin bugs (Heteroptera, Reduviidae) at least, the male and female genitalic structures of several subfamilies are poorly or totally unknown. The genital structure is mostly symmetric within Saicinae genera, but male genital asymmetry has been recorded in Gallobelgicus, Polytoxus, and recently Pseudosaica. The subfamily has been considered as closely related to Emesinae and Visayanocorinae but this hypothesis has never been tested using a comprehensive taxa sampling, being a constraint to test morphological traits changes or exploring characters' evolution hypotheses. Here, we compiled a morphological data set of 170 characters that includes external morphological characters and genitalia of both sexes of Saicinae which was analyzed cladistically including 55 terminals, comprising 16 genera (64% of the generic diversity), 43 species of Saicinae and 12 outgroups. Saicinae was recovered as polyphyletic, Saicireta correntina is recovered as sister-species of Empicoris armatus + Collartida (Emesinae), Oncerotrachelus, Carayonia (Visayanocorinae), and the Clade Saicinae sensu stricto. Carayonia orientalis is recovered as sister-species of Saicinae sensu stricto. Ancestral state reconstruction of symmetry of the male genitalia shows an ancestor with symmetric male genitalia, two independent emergences of asymmetrical male genitalia within Saicinae sensu stricto, and the asymmetrical endosomal sclerites appearing before the other asymmetric traits.


Non-Tuberculous Mycobacterial Pulmonary Disease identified during community-based screening for Mycobacterium Tuberculosis: a case report.
There is a rising prevalence of Non-Tuberculous Mycobacterial (NTM) disease in sub-Saharan Africa identified on culture specimens. However, distinguishing mycobacterial colonisations from infection from identified NTMs on culture in the sub-Saharan Africa setting remains to be established. A 49-year-old man presented with the cardinal symptoms of tuberculosis (TB) in a community TB prevalence survey in Blantyre, Malawi. Mycobacteriology was atypical, prompting a line probe assay which revealed Mycobacterium avium complex (MAC) species. The epidemiology of Mycobacterium tuberculosis complex (MTBC) is better known than that of NTM. Up-scaling culture and speciation may be a solution to this gap in knowledge of the burden of disease of NTM. Like most resource-poor settings, TB culture is not routinely done in the diagnosis and management of TB in Malawi. Furthermore, the treatment of NTM is not analogous to that of MTBC. The multi-drug regimens used for NTM disease treatment includes a newer macrolide (azithromycin, clarithromycin), ethambutol, and rifamycin, and require prolonged durations of therapy aimed at facilitating clearance of the mycobacteria and minimizing the emergence of drug resistance. Clinicians must thus be aware of this rising burden of NTM disease and consider other diagnostic options to better investigate this disease in patients.


Psychological tension and closeness to others: stress and interpersonal distance preference.
The prediction that increased tension would lead to a preference for greater distance from others was tested on 40 male and 40 female Ss approached in eight natural settings of high or low tension and their distance preference measured. Ss in the four higher-tension situations indicated a preference for significantly more distance. Self-reported tension was correlated significantly and positively with the distance preferred across all eight situations. There was no effect of sex.


West syndrome in an infant with vitamin B12 deficiency in the absence of macrocytic anaemia.
Vitamin B(12) deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B(12) deficiency can be difficult when the typical macrocytic anaemia is absent. We report the case of a 10-month-old female diagnosed with West syndrome associated with vitamin B(12) deficiency but without macrocytic anaemia caused by nutritional inadequacy in the mother. The patient's motor skills and cognitive development were normal until she was 9 months old, when she began to exhibit a series of sudden flexions of the head, trunk, arms, and legs. She was exclusively breast-fed and had received no vitamin supplementation. Results of electroencephalography (EEG) indicated modified hypsarrhythmia and the patient was diagnosed as having West syndrome. Synthetic adrenocorticotropic hormone was administered and although her spasms had resolved, the patient remained apathic and could not sit without assistance. EEG results indicated generalized slow activity. After she was diagnosed as having vitamin B(12) deficiency, parenteral treatment with vitamin B(12) was initiated. Her symptoms resolved and EEG was completely normal. When she was 20 months old she exhibited an age-appropriate developmental and neurological profile. To our knowledge, this is the first report of West syndrome as a presenting symptom of vitamin B(12) deficiency.


Effect of doping on surface reactivity and conduction mechanism in samarium-doped ceria thin films.
A systematic study by reversible and hysteretic electrochemical strain microscopy (ESM) in samples of cerium oxide with different Sm content and in several working conditions allows disclosing the microscopic mechanism underlying the difference in electrical conduction mechanism and related surface activity, such as water adsorption and dissociation with subsequent proton liberation. We have measured the behavior of the reversible hysteresis loops by changing temperature and humidity, both in standard ESM configuration and using the first-order reversal curve method. The measurements have been performed in much smaller temperature ranges with respect to alternative measuring techniques. Complementing our study with hard X-ray photoemission spectroscopy and irreversible scanning probe measurements, we find that water incorporation is favored until the doping with Sm is too high to allow the presence of Ce3+. The influence of doping on the surface reactivity clearly emerges from all of our experimental results. We find that at lower Sm concentration, proton conduction is prevalent, featured by lower activation energy and higher electrical conductivity. Defect concentrations determine the type of the prevalent charge carrier in a doping dependent manner.


Strong IgG isotypic antibody response in sowdah type onchocerciasis.
Persons exposed to Onchocerca volvulus express differences in manifestations of onchocerciasis ranging from hyporeactive (generalized) to hyperreactive (sowdah) forms; absence of disease is seen in endemic normal persons. Analysis of the IgG isotypic antibody response to O. volvulus extracts and nonparasite ubiquitous antigens in 92 West Africans revealed highest anti-O. volvulus IgG1 and IgG2 responses in sowdah, high levels in the generalized form, and low antibody levels in endemic normal persons. Nonexposed persons had no antibodies. A significant IgG3 antibody response was detected only in sowdah, while high IgG4 levels occurred in both polar groups but were absent in both control groups. Isotypic responses to antigens unrelated to O. volvulus were similar in all groups but showed higher IgG1 and IgG2 levels in sowdah. Sowdah patients had high levels of Ro/SS-A antibodies, circulating immune complexes, and eosinophil cationic protein. These results document a strong B cell response in African sowdah and indicate variations in immune responsiveness.


Comparison of baseline characteristics, clinical features, angiographic results, and early outcomes in men vs women with acute myocardial infarction undergoing primary coronary intervention.
Women have had a higher early mortality rate than men after acute myocardial infarction (AMI) in the prethrombolytic and thrombolytic eras. Primary percutaneous coronary intervention (PCI) has been shown to significantly improve survival of patients with AMI, and to be superior to thrombolytic therapy in terms of immediate restoration of normal flow in the infarct-related artery and reduction of recurrent ischemic events. However, the effect of primary PCI on early outcomes of women vs men remains unknown. Therefore, we examined whether there was any difference in term of 30-day mortality between women and men after primary PCI. Between May 1993 and April 2002, primary PCI was performed in 1,032 consecutive patients (15.3% women and 84.7% men) with AMI. The overall successful reperfusion (final Thrombolysis in Myocardial Infarction grade 3 flow) and 30-day morality rates were 84.0% and 8.5%, respectively. The rate of successful reperfusion did not differ between women and men (84.8% vs 83.9%, p = 0.77). However, mortality at 30 days was significantly higher in women than in men (14.6% vs 7.4%, p = 0.003). In comparison with men, women were older; had significantly higher incidences of hypertension, diabetes mellitus, complete atrioventricular block, and right ventricular infarction; and had longer times of reperfusion (all p values < 0.05). During hospitalization, advanced congestive heart failure (New York Heart Association class 3 or greater), free wall rupture, and major bleeding complications were more likely to occur in women than in men (all p values < 0.05). Compared with men, the unadjusted odds ratio for 30-day death among women was 2.12 (95% confidence interval [CI], 1.27 to 3.53). After adjusting for age, the odds ratio was substantially reduced to 1.66 (95% CI, 0.98 to 2.79). Further adjustment for age and other variables further reduced the odds ratio to 1.06 (95% CI, 0.53 to 2.14). A gender gap of 30-day mortality existed between women and men with AMI that could not be altered by primary PCI. However, this gap was only an apparent one, and was not truly related to gender alone. In comparison with men, women were older, had significantly higher incidences of comorbidities and major untoward clinical events, and had longer times of reperfusion, which could help explain why the 30-day mortality rate was higher in women than in men.


Pharmacological conversion of gut epithelial cells into insulin-producing cells lowers glycemia in diabetic animals.
As a highly regenerative organ, the intestine is a promising source for cellular reprogramming for replacing lost pancreatic β cells in diabetes. Gut enterochromaffin cells can be converted to insulin-producing cells by forkhead box O1 (FoxO1) ablation, but their numbers are limited. In this study, we report that insulin-immunoreactive cells with Paneth/goblet cell features are present in human fetal intestine. Accordingly, lineage-tracing experiments show that, upon genetic or pharmacologic FoxO1 ablation, the Paneth/goblet lineage can also undergo conversion to the insulin lineage. We designed a screening platform in gut organoids to accurately quantitate β-like cell reprogramming and fine-tune a combination treatment to increase the efficiency of the conversion process in mice and human adult intestinal organoids. We identified a triple blockade of FOXO1, Notch, and TGF-β that, when tested in insulin-deficient streptozotocin (STZ) or NOD diabetic animals, resulted in near normalization of glucose levels, associated with the generation of intestinal insulin-producing cells. The findings illustrate a therapeutic approach for replacing insulin treatment in diabetes.


Gastrointestinal involvement of dialysis-related amyloidosis.
Beta-2 microglobulin-related amyloids were found in gastric biopsy specimens from 3 of 11 patients who had been on hemodialysis more than 10 years and examined. The deposits were found not only in arteriolar walls but also in lamina propria and muscle tissue. In another patient who was on hemodialysis for 8 years, beta 2-microglobulin-related amyloids were found in the muscle layer of operatively resected colon. These four patients also had the same substance deposited in the osteoarticular system. The results suggest the systemic involvement of beta 2-microglobulin-related amyloidosis in patients on long-term hemodialysis.


Frequency and irregularity of heart rate in drivers suspected of driving under the influence of cannabis.
Delta 9-tetrahydrocannabinol (THC) is the major active component of cannabis. Cardiovascular effects of THC have previously been reported: tachycardia after intake, but also bradycardia at higher doses. The purpose of this study was, firstly, to investigate the frequency and irregularity of heart rate in a group of cannabis users in their natural surroundings. We also compared THC-positive drivers with a regular pulse with THC-positive drivers with an irregular pulse. The division of Forensic Toxicology and Drug Abuse (DFTDA) at the Norwegian Institute of Public Heath analyzes blood samples from all drivers suspected of driving under the influence of drugs. We studied pulse rate and regularity in 502 THC-positive drivers who tested negative for other substances. As a control group, we randomly selected 125 drug-negative cases from the database of the DFTDA; no alcohol, narcotics, or medicinal drugs of abuse were detected. The Delta9-THC-positive drivers had a higher mean pulse rate than the control group [82.8 beats/min (SD 16.3) versus 75.6 beats/min (SD 9.2)] and more cases with tachycardia were detected in the Delta9-THC-positive group (19.4% versus 1.6%). There was only one driver with an irregular heart beat in the control group, while there were nine among the Delta9-THC-positive drivers. The drivers with an irregular pulse were over-represented amongst those with the lowest blood Delta9-THC concentrations. This report represents a large study of subjects in a real-life situation and includes observations on pulse frequency, regularity, and blood Delta9-THC concentration. A substantial fraction of Delta9-THC-positive drivers had tachycardia, but there was no correlation between blood Delta9-THC concentration and pulse rate in the present study. We had no further diagnostic information on the cause of the pulse irregularities, but our results indicate that occasional users of cannabis tend to have irregular heart rates at low THC concentrations and at low pulse rates.


Influence of surface roughness on field emission of electrons from carbon nanotube films.
Electron field emission properties of a nanotube film are influenced not only by a field enhancement factor of carbon nanotubes (CNTs) beta(CNT) but also by that of film morphology beta(P). A simple method to separate beta(P), and beta(CNT) is proposed by using their different dependences on the cathode-anode distance. Analyses conducted for CNT emitters with rough surface exhibit that beta(P) ranges from 1 to approximately 4.5. The separated beta(CNT) values are in good agreement with the CNT geometries observed by a scanning electron microscope. Variation in beta(P)-values is ascribed to the surface roughness of the CNT films.


Malnutrition is an unusual cause of decreased muscle mass in chronic kidney disease.
Patients with chronic kidney disease (CKD), including those who are treated with hemodialysis, frequently develop hypoalbuminemia and a decrease in body weight. These abnormalities are usually attributed to malnutrition, but true malnutrition (ie, a disorder due to an abnormal diet) is rarely the mechanism causing decreased protein stores. Hypoalbuminemia is closely related to evidence of inflammation, and a decrease in muscle mass is caused by activation of muscle protein breakdown. In uremic rodents and patients, the initial step in the loss of muscle protein is activation of caspase-3, which cleaves the complex structure of muscle to provide substrates for the ubiquitin-proteasome pathway (UPP). The activity of caspase-3 can be detected by the presence of a characteristic 14-kDa actin fragment in the insoluble fraction of a muscle biopsy specimen. Abnormalities in cell signaling activate caspase-3 and the UPP; a key abnormality is decreased activity in the phosphatidylinositol-3-kinase/Akt pathway, leading to activation of caspase-3 and a specific E3 ubiquitin conjugating enzyme, atrogin-1/MAFbx. Inflammatory cytokines also represent a potential cell signaling abnormality that activates muscle protein breakdown, possibly because cytokines activate the E3 ubiquigin conjugating enzyme, MuRF1. An understanding of these pathways could help the clinician to identify therapeutic targets for preventing loss of muscle protein.


Serological evidences of bovine herpesvirus-1 infection in bovines of organized farms in India.
Bovine herpesvirus type-1 (BHV-1) is an important pathogen of cattle causing a variety of clinical signs, including the upper respiratory tract infection, infectious bovine rhinotracheitis (IBR). Infectious bovine rhinotracheitis, a highly infectious disease of cattle and buffaloes, occurs throughout the world including India. The present study based on micro-serum neutralization test reports the sero-epidemiology of BHV-1 infection in cattle and buffaloes from different parts of India. Serum samples from cattle, bulls, buffalo bulls and yaks were screened for BHV-1 antibodies. A total of 1115 serum samples were screened, and a total of 437 (39.2%) serum samples were found positive and 678 (60.8%) serum samples were found negative. Overall 168 (38.0%) cattle, 17 (85.0%) buffalo, 212 (38.6%) bulls, 8 (13.5%) buffalo bulls and 32 (71.1%) yaks were found positive for BHV-1 antibodies. State wise, Assam had highest seropositivity of 71.1% for yaks, Madhya Pradesh had 68.9% for cattle and Meghalaya was negative for the presence of antibodies to BHV-1 in cattle.


ALP & FALP: C++ libraries for pairwise local alignment E-values.
Pairwise local alignment is an indispensable tool for molecular biologists. In real time (i.e. in about 1 s), ALP (Ascending Ladder Program) calculates the E-values for protein-protein or DNA-DNA local alignments of random sequences, for arbitrary substitution score matrix, gap costs and letter abundances; and FALP (Frameshift Ascending Ladder Program) performs a similar task, although more slowly, for frameshifting DNA-protein alignments. To permit other C++ programmers to implement the computational efficiencies in ALP and FALP directly within their own programs, C++ source codes are available in the public domain at http://go.usa.gov/3GTSW under 'ALP' and 'FALP', along with the standalone programs ALP and FALP. firstname.lastname@example.com Supplementary data are available at Bioinformatics online.


The effect of a designated tool on person-centred goal identification and service planning among older people receiving homecare in New Zealand.
This study sought to determine the ability of a designated tool developed to identify client-directed goals in a sample of older people referred for homecare. A retrospective pre/post-intervention design was used and a total of 360 older people in an urban centre in New Zealand were included in the analysis. All clients receiving services at the time of data collection (July 2007) who were referred for service provision between July 2003 and the implementation in January 2007 of a restorative model of homecare were included in the analysis. The restorative model of homecare included a designated goal-facilitation tool [Towards Achieving Realistic Goal in Elders Tool (TARGET)]. Prior to the use of TARGET, participants had a goal recorded for their home-care episode in 31 cases (8.6%), whereas following the implementation of TARGET, goals were recorded in 339 cases (94.2%). At a quarterly review, eight clients (2.2%) achieved their goal prior to TARGET, whereas 172 clients (47.8%) fully achieved their goal when TARGET was utilised. Within the sample, multinomial logistic regression showed that the use of TARGET significantly improved goal attainment. Furthermore, moderate-to-severe cognitive impairment significantly reduced the successful attainment of goals. The study highlighted the importance of a designated tool for facilitating older people to set goals that are then used in developing support plans to structure services to assist them in the home. The need for alternative strategies for goal setting for people with significant cognitive impairment was highlighted. This study, in attempting to determine the effect of a goal-facilitation tool as a driver for quality improvement in homecare, had an observational comparative design, this being the most pragmatic option to assess the feasibility of TARGET prior to further work being undertaken. The results do show that in this sample of older people receiving homecare, the use of TARGET led to a greater proportion of goal identification, higher rates of goal attainment and a more diverse range of categories of goals than traditional non-structured methods of goal setting.


Total Sleep Deprivation Triggers Greater Activation in the Parietal Brain in the Visual Working Memory Updating Processes: An Event-Related Potentials Study.
Working memory functions are known to be altered after total sleep deprivation (TSD). However, few studies have explored the deficits of working memory updating (WMU) after TSD, or the underlying electrophysiological mechanisms of these alterations. In the current exploratory study, we enrolled 14 young male volunteers who performed two kinds of WMU tasks-spatial and object two-back tasks-with simultaneous electroencephalography recordings under two sleep conditions: a normal sleep baseline condition and after 36 h of TSD. Repeated-measures analysis of variance showed that compared with those at baseline, the rates of correct responses in the WMU tasks decreased significantly after TSD. Analysis of event-related potentials revealed that the average amplitude of P3 components decreased significantly in the frontal and central brain regions and increased significantly in the parietal brain regions. Our findings suggest that TSD damages WMU behavior, impairs cognitive functions in the frontal and central brain regions, and triggers greater activation in the parietal brain regions. This is the first study to report the existence of event-related compensatory neural activity. This event-related compensatory effect may provide a new perspective for understanding the mechanisms underlying the influences triggered by sleep loss.


Quantitative proteomic analysis of extracellular matrix extracted from mono- and dual-species biofilms of Fusobacterium nucleatum and Porphyromonas gingivalis.
The Gram-negative bacteria Fusobacterium nucleatum and Porphyromonas gingivalis are members of a complex dental biofilm associated with periodontal disease. In this study, we cultured F. nucleatum and P. gingivalis as mono- and dual-species biofilms, and analyzed the protein composition of the biofilms extracellular polymeric matrix (EPM) by high-resolution liquid chromatography-tandem mass spectrometry. Label-free quantitative proteomic analysis was used for identification of proteins and sequence-based functional characterization for their classification and prediction of possible roles in EPM. We identified 542, 93 and 280 proteins in the matrix of F. nucleatum, P. gingivalis, and the dual-species biofilm, respectively. Nearly 70% of all EPM proteins in the dual-species biofilm originated from F. nucleatum, and a majority of these were cytoplasmic proteins, suggesting an enhanced lysis of F. nucleatum cells. The proteomic analysis also indicated an interaction between the two species: 22 F. nucleatum proteins showed differential levels between the mono and dual-species EPMs, and 11 proteins (8 and 3 from F. nucleatum and P. gingivalis, respectively) were exclusively detected in the dual-species EPM. Oxidoreductases and chaperones were among the most abundant proteins identified in all three EPMs. The biofilm matrices in addition contained several known and hypothetical virulence proteins, which can mediate adhesion to the host cells and disintegration of the periodontal tissues. This study demonstrated that the biofilm matrix of two important periodontal pathogens consists of a multitude of proteins whose amounts and functionalities vary largely. Relatively high levels of several of the detected proteins might facilitate their potential use as targets for the inhibition of biofilm development.


The Feasibility of Xpert MTB/RIF Testing to Detect Rifampicin Resistance among Childhood Tuberculosis for Prevalence Surveys in Northern China.
Drug resistance surveillance is crucial for control of drug-resistant tuberculosis (TB). However, limited data exists on the burden of drug-resistant TB in children. The goal of this work was to generate prevalence data regarding rifampicin- (RIF-) resistant childhood TB in northern China and to test the feasibility of Xpert for surveying pediatric TB drug resistance prevalence. We enrolled 362 clinically diagnosed childhood TB patients and collected sputum, gastric lavage aspirate (GLA), bronchoalveolar lavage fluid (BALF), and cerebral spinal fluid (CSF) samples. Xpert and solid culture were utilized to detect RIF resistance. The detection rate of Xpert-positive TB among new clinically diagnosed TB cases was 38.4% (139/362), significantly higher than that of solid culture-positive TB (16.3%, 59/362, P < 0.01). Notably, Xpert-positive rates differed significantly by sample type, with the highest positive rate for GLA (51.2%). The unit testing costs per RIF-resistant TB patient were $828.41 for solid culture and $761.86 for Xpert. Our data demonstrate that the prevalence of RIF resistance among childhood TB cases in our study (6.9%) is comparable to the national RIF resistance prevalence level of new cases (6.7%). In addition, Xpert is superior to the solid culture for RIF resistance survey in the childhood TB patients.


[The extracellular pH and membrane fluidity on intracellular retention of adriamycin].
Using flow cytometry, we evaluated the effect of extracellular pH on intracellular retention of adriamycin (ADR) in K562 cells. The intracellular retention of ADR at pH 7.60 increased markedly compared to the level at pH 7.30. The cell membrane fluidity was measured by spin labeled electron spin resonance techniques. The cell membrane fluidity at pH 7.60 decreased significantly in comparison with those at pH 7.45 and 7.30. The antiproliferative effect of ADR at pH 7.60 was significantly augmented compared to those at pH 7.45 and 7.30. These results suggested that the augmentation of ADR-induced antiproliferative effect by extracellular alkalic shift was caused by membrane rigidity of lipid bilayer, resulting in the decrease of ADR efflux due to less function of P-glycoprotein.


AP-1 and ARF1 control endosomal dynamics at sites of FcR mediated phagocytosis.
Phagocytosis, the mechanism of ingestion of large material and microorganisms, relies on actin polymerization and on the focal delivery of intracellular endocytic compartments. The molecular mechanisms involved in the formation and delivery of the endocytic vesicles that are recruited at sites of phagocytosis are not well characterized. Here we show that adaptor protein (AP)-1 but not AP-2 clathrin adaptor complexes are recruited early below the sites of particle attachment and are required for efficient receptor-mediated phagocytosis in murine macrophages. Clathrin, however, is not recruited with the AP complexes. We further show that the recruitment of AP-1-positive structures at sites of phagocytosis is regulated by the GTP-binding protein ARF1 but is not sensitive to brefeldin A. Furthermore, AP-1 depletion leads to increased surface levels of TNF-alpha, a cargo known to traffic through the endosomes to the plasma membrane upon stimulation of the macrophages. Together, our results support a clathrin-independent role for AP complexes in endosomal dynamics in macrophages by retaining some cargo proteins, a process important for membrane remodeling during phagocytosis.


Cervical Total Disk Replacement: Available Implant Size Matters.
This study was a post hoc analysis of data collected from 2 Food and Drug Administration (FDA) Investigational Device Exemption (IDE) trials. The purposes of this study were to: (1) measure disk space heights adjacent to the level to be treated with a total disk replacement (TDR); (2) analyze cervical disk space heights to be replaced with TDR; and (3) investigate the frequency of use of a smaller height TDR when available. Cervical TDR produces outcomes noninferior or superior to anterior cervical discectomy and fusion. While the restoration of the height of a collapsed, degenerated disk is a surgical goal, there are potential problems with overdistracting the segment with an implant. Disk heights were measured using radiographs from the 1-level Simplify Cervical Artificial Disk IDE trial, producing values for 259 levels adjacent to the treated level and 162 treated levels. The device is available in 4, 5, and 6 mm heights. The 4 mm height became available only after treatment was 13% complete in the single-level trial and was available for all of the 2-level trial. Measurements of 259 adjacent levels found that 55.2% of disk spaces had a height of <4 mm. Among operated levels, 82.7% were <4 mm. When a 4 mm TDR was available, it was used in 38.4% of operated levels in the 1-level trial and 54.3% of levels in the 2-level trial. Among nonoperated levels, 55.2% were of height <4 mm, suggesting that TDRs of greater heights may potentially overdistract the disk space. The 4 mm TDR was selected by surgeons in 49.4% of all implanted levels, suggesting a preference for smaller TDR height. Further investigation is warranted to determine if the lower height implants are related to clinical and/or radiographic outcomes. Level III.


Building Smarter Aqueous Batteries.
Amidst the global trend of advancing renewable energies toward carbon neutrality, energy storage becomes increasingly critical due to the intermittency of renewables. As an alternative to lithium-ion batteries (LIBs), aqueous batteries have received growing attention for large-scale energy storage due to their economical and safe features. Despite the fruitful achievements at the material level, the reliability and lifetime of aqueous batteries are still far from satisfactory. Alike LIBs, integrating smartness is essential for more reliable and long-life aqueous batteries via operando monitoring and automatic response to extreme abuses. In this review, recent advances in sensing techniques and multifunctional battery-sensor systems together with self-healing methods in aqueous batteries is summarized. The significant role of artificial intelligence in designing and optimizing aqueous batteries with high efficiency is also highlighted. Ultimately, it is extrapolated toward the future and present the humble perspective for building smarter aqueous batteries.


An Explanation of the Influence on Deciding which Type of Foot Strike to Use when Running Barefoot or in Minimalistic Shoes.
Buying minimalistic shoes does not mean that you know how to use them. Salespersons are rarely competent to give adequate advice how to transition to new shoes. The same happens when someone chooses to run barefoot. So, the aim of the present experiment was to find out whether giving or not giving an explanation of the correct technique of foot placement in barefoot running and running in a minimalistic shoe influences the frequency of rear-foot strikes in natural, rear foot strikers when running barefoot or in minimalistic shoes. Thirty-nine subjects (age =34.9 ± 6.9 years, height = 174 ± 9 cm, mass = 73.1 ± 13.8 kg), randomly divided into four groups participated in this experiment. Subjects in groups 1 and 3 did not receive an explanation, while groups 2 and 4 did. Besides the difference in explanation, there was also a difference in the shoes worn during the intervention. Subjects in the groups 1 and 2 ran barefoot, while subjects in groups 3 and 4 ran in minimalistic shoes. The initial state of the foot strike patterns was measured in classic running shoes. During the intervention subjects ran according to the group they were in. 80% of the subjects in groups 1 and 3 took the most steps in a rear-foot strike pattern (Median =100) while only 21% of the subjects in groups 2 and 4 took the most steps in a rear-foot strike pattern (Median = 15.7), U = 64, z = 3.619, p (0.00) < 0.05, r = -0.58. The results show that an explanation and dem-onstration of the correct technique of foot placement in barefoot running and running in a minimalistic shoe is important when someone decides to switch from classic running shoes to minimalistic shoes or to go barefoot.


Complete nucleotide sequence of plasmid Rts1: implications for evolution of large plasmid genomes.
Rts1, a large conjugative plasmid originally isolated from Proteus vulgaris, is a prototype for the IncT plasmids and exhibits pleiotropic thermosensitive phenotypes. Here we report the complete nucleotide sequence of Rts1. The genome is 217,182 bp in length and contains 300 potential open reading frames (ORFs). Among these, the products of 141 ORFs, including 9 previously identified genes, displayed significant sequence similarity to known proteins. The set of genes responsible for the conjugation function of Rts1 has been identified. A broad array of genes related to diverse processes of DNA metabolism were also identified. Of particular interest was the presence of tus-like genes that could be involved in replication termination. Inspection of the overall genome organization revealed that the Rts1 genome is composed of four large modules, providing an example of modular evolution of plasmid genomes.


As Long as Parents Can Accept Them: Medical Disclosure, Risk, and Disability in Twentieth-Century American Adoption Practice.
This article reviews adoption debates about the disclosure of children's medical history in the twentieth century, noting shifts in the prescription of how much and what to tell adoptive applicants. I look at how adoption professional debates throughout the twentieth century around the disclosure of a child's medical history reveal the ways in which these professionals tried to deal with issues of predictability, risk, adoptability, and acceptability when it came to the persistent question of disability in adoptive family making. I consider how this management is similar to and different from histories of reproduction. I argue that as child eligibility gradually expanded to include children labeled disabled, and as adoption moved from a being a parent-centered practice to a child-centered one, professionals more intensely negotiated the management and communication of disability risk as a way to both mitigate the possibility of a failed placement and to facilitate a successful one.


Additional genetic abnormalities significantly worsen poor prognosis associated with 1q21 amplification in multiple myeloma patients.
We investigated the prognostic value of amp(1q21) alone and in combination with other abnormalities in newly diagnosed myeloma patients. The study group consisted of 104 patients treated with various induction regimens, mostly thalidomide based (87 patients). Amp(1q21) was detected in 49 (47.1%) of patients; in 26 (25.0%) cases, it was combined with del(13q14), in 7 (6.7%) with del(17p13) and in 15 (14.4%) with t(4;14)(p16;q32). The response rate was significantly better in amp(1q21)-negative than in amp(1q21)-positive patients (74.5% vs 55.1%, p = 0.025; complete response 18.2% vs 4.1%, p = 0.024). The median progression-free survival (PFS) was 33.9 months in patients without amp(1q21) and 10.3 months with this aberration (p = 0.002). The presence of additional abnormalities resulted in significantly shortened PFS when compared with patients with isolated amp(1q21): coexisting del(13q14) resulted in 7.8 vs 29.0 months of PFS (p = 0.024) and del(17p13) resulted in 4.0 vs 24.9 months of PFS (p = 0.034). The presence of amp(1q21) significantly influenced overall survival (OS) as well as PFS resulting in the median OS of 26.6 vs 62.4 months (p = 0.018) in patients without amp(1q21). The presence of additional genetic abnormalities significantly affected OS when compared with patients carrying isolated amp(1q21): for del(13q14) 18.9 vs 58.4 months (p = 0.004) and for del(17p13) 12.0 vs 46.5 months (p = 0.036). On multivariate analysis amp(1q21), del(13q14) and del(17p13) were found to be an independent adverse predictors of shorter PFS and OS. Our results showed that the presence of amp(1q21) was associated with poor prognosis. Moreover additional genetic abnormalities made PFS and OS further shortened.


Household transmission of Streptococcus pneumoniae among siblings with acute otitis media.
Nasopharyngeal transmission of Streptococcus pneumoniae was evaluated among 23 siblings with acute otitis media (AOM). Restriction fragment length polymorphism revealed that the nasopharyngeal strains were identical between siblings in 12 of 13 clusters of AOM experienced in 11 families. This study demonstrated person-to-person transmission of S. pneumoniae, especially drug-resistant strains, among siblings with AOM.


[Lysine and arginine requirement of "Ustilago cynodontis" 4001 yeast-like cells. I. --Growth in the presence and in the absence of lysine (author's transl)].
For optimal growth, the yeast-like cells of Ustilago cynodontis 4001 (originating from the mycelium 4001 prototroph forms) require the presence of both arginine and lysine. However, in the absence of lysine, growth does occur, but two exponential growth phases can then be observed: a pseudo-lag phase during which the growth rate is slow, and a second, true exponential phase. The initial OD of the culture and the arginine concentration of the medium do not appear to affect the duration of the pseudo-lag phase. The arginine concentration does, however, affect the growth yield. Upon addition of lysine to the culture medium, the period of the pseudo-lag phase is reduced and the growth rate increased. The pseudo-lag phase can be completely suppressed by the addition of adequate amounts of lysine. In the presence of lysine and in the absence of arginine, cells are not capable of multiplication. Addition of arginine initiates growth; whether or not a lag phase occurs depends on the quantity of arginine added. The successive inoculation of cells into lysine-free medium leads to suppression of the pseudo-lag phase but only after three or four passages. Therefore it does not seem that there is selection of cells which do not require lysine during the pseudo-lag phase. It is shown that it is not the modification of the culture medium which suppresses the lysine requirement: the cells which are put to grow in the supernatant of a culture in which a pseudo-lag phase had taken place behave in the same way that when they are inoculated in a new medium. The modification of the cell metabolism itself is discussed.


Georg Schmorl Prize of the German Spine Society (DWG) 2020: new biomechanical in vitro test method to determine subsidence risk of vertebral body replacements.
Prevention of implant subsidence in osteoporotic (thoraco)lumbar spines is still a major challenge in spinal surgery. In this study, a new biomechanical in vitro test method was developed to simulate patient activities in order to determine the subsidence risk of vertebral body replacements during physiologic loading conditions. The study included 12 (thoraco)lumbar (T11-L1, L2-L4) human specimens. After dorsal stabilisation and corpectomy, vertebral body replacements (VBR) with (a) round centrally located and (b) lateral end pieces with apophyseal support were implanted, equally distributed regarding segment, sex, mean BMD ((a) 64.2 mgCaHA/cm3, (b) 66.7 mgCaHA/cm3) and age ((a) 78 years, (b) 73.5 years). The specimens were then subjected to everyday activities (climbing stairs, tying shoes, lifting 20 kg) simulated by a custom-made dynamic loading simulator combining corresponding axial loads with flexion-extension and lateral bending movements. They were applied in oscillating waves at 0.5 Hz and raised every 100 cycles phase-shifted to each other by 50 N or 0.25°, respectively. The range of motion (ROM) of the specimens was determined in all three motion planes under pure moments of 3.75 Nm prior to and after implantation as well as subsequently following activities. Simultaneously, subsidence depth was quantified from fluoroscope films. A mixed model (significance level: 0.05) was established to relate subsidence risk to implant geometries and patients' activities. With this new test method, simulating everyday activities provoked clinically relevant subsidence schemes. Generally, severe everyday activities caused deeper subsidence which resulted in increased ROM. Subsidence of lateral end pieces was remarkably less pronounced which was accompanied by a smaller ROM in flexion-extension and higher motion possibilities in axial rotation (p = 0.05). In this study, a new biomechanical test method was developed that simulates physiologic activities to examine implant subsidence. It appears that the highest risk of subsidence occurs most when lifting heavy weights, and into the ventral part of the caudal vertebra. The results indicate that lateral end pieces may better prevent from implant subsidence because of the additional cortical support. Generally, patients that are treated with a VBR should avoid activities that create high loading on the spine.


Numerical study of roughness distributions in nonlinear models of interface growth.
We analyze the shapes of roughness distributions of discrete models in the Kardar, Parisi, and Zhang (KPZ) and in the Villain, Lai, and Das Sarma (VLDS) classes of interface growth, in one and two dimensions. Three KPZ models in d=2 confirm the expected scaling of the distribution and show a stretched exponential tail approximately as exp(-x0.8), with a significant asymmetry near the maximum. Conserved restricted solid-on-solid models belonging to the VLDS class were simulated in d=1 and d=2. The tail in d=1 has the form exp(-x2) and, in d=2, has a simple exponential decay, but is quantitatively different from the distribution of the linear fourth-order (Mullins-Herring) theory. It is not possible to fit any of the above distributions to those of 1/f(alpha) noise interfaces, in contrast with recently studied models with depinning transitions.


[Sacro-iliac osteochondritis (author's transl)].
Sacro-iliac osteochondritis is difficult to recognize, it is rather frequently a case of diagnosis by elimination, which can be only confirmed by the course. Its prognosis is excellent. The predominance of lesions on the iliac edge reflects the affinity of this epiphysitis for the accessory iliac ossification point.


[Preparation of herpetin lyophilized liposome and evaluation on its safety and pharmacodynamics].
In this study, the herpetin (HPT) lyophilized liposome was prepared, and its saftey and pharmacodynamics were evaluated. HPT lyophilized liposome was prepared by thin-film ultrasonication method. The lyoprotectant was optimized using particle size and encapsulation efficiency as indexes. Then, the influencing factors of HPT lyophilized liposome were investigated. In addition, preliminary safety and therapy efficiency of HPT lyophilized liposome to liver injury induced by CCl4 in the mice. The optimal lyoprotectant was 5% sucrose plus 5% lactose and the dispersed HPT lyophilized liposomes were spherical with the mean diameter of (107.0 ± 1.2) nm and the mean encapsulation efficiency of (99.7 ± 0.50)%. The lyophilized powder was sensitive to temperature, humidity and illumination. None of hemolysis, hemagglutination and vein irritation was observed after intravenous injection of HPT lyophilized liposomes into rabbits. HPT lyophilized liposome showed obviously therapy efficiency to liver injury induced by CCl4 in the mice. The improvements of ALT, AST and ALP were better than that in HPT free drug. The obtained HPT lyophilized liposome met the standard of CP with fine particle size and encapsulation efficiency after dispersion. The HPT lyophilized liposome showed good safety and enhanced the treatment efficacy of HPT. The HPT lyophilized liposome should be stored in low temperature, sealed condition far away from light.


Identification of a second two-component signal transduction system that controls fosfomycin tolerance and glycerol-3-phosphate uptake.
Particular interest in fosfomycin has resurfaced because it is a highly beneficial antibiotic for the treatment of refractory infectious diseases caused by pathogens that are resistant to other commonly used antibiotics. The biological cost to cells of resistance to fosfomycin because of chromosomal mutation is high. We previously found that a bacterial two-component system, CpxAR, induces fosfomycin tolerance in enterohemorrhagic Escherichia coli (EHEC) O157:H7. This mechanism does not rely on irreversible genetic modification and allows EHEC to relieve the fitness burden that results from fosfomycin resistance in the absence of fosfomycin. Here we show that another two-component system, TorSRT, which was originally characterized as a regulatory system for anaerobic respiration utilizing trimethylamine-N-oxide (TMAO), also induces fosfomycin tolerance. Activation of the Tor regulatory pathway by overexpression of torR, which encodes the response regulator, or addition of TMAO increased fosfomycin tolerance in EHEC. We also show that phosphorylated TorR directly represses the expression of glpT, a gene that encodes a symporter of fosfomycin and glycerol-3-phosphate, and activation of the TorR protein results in the reduced uptake of fosfomycin by cells. However, cells in which the Tor pathway was activated had an impaired growth phenotype when cultured with glycerol-3-phosphate as a carbon substrate. These observations suggest that the TorSRT pathway is the second two-component system to reversibly control fosfomycin tolerance and glycerol-3-phosphate uptake in EHEC, and this may be beneficial for bacteria by alleviating the biological cost. We expect that this mechanism could be a potential target to enhance the utility of fosfomycin as chemotherapy against multidrug-resistant pathogens.


Genetics and cell biology of building specific synaptic connectivity.
The assembly of specific synaptic connections during development of the nervous system represents a remarkable example of cellular recognition and differentiation. Neurons employ several different cellular signaling strategies to solve this puzzle, which successively limit unwanted interactions and reduce the number of direct recognition events that are required to result in a specific connectivity pattern. Specificity mechanisms include the action of contact-mediated and long-range signals that support or inhibit synapse formation, which can take place directly between synaptic partners or with transient partners and transient cell populations. The molecular signals that drive the synaptic differentiation process at individual synapses in the central nervous system are similarly diverse and act through multiple, parallel differentiation pathways. This molecular complexity balances the need for central circuits to be assembled with high accuracy during development while retaining plasticity for local and dynamic regulation.


Generalized Effects of Naturalistic Social Communication Intervention for Minimally Verbal Children with Autism.
JASP-EMT, the combined Enhanced Milieu Teaching (EMT) and Joint Attention, Structured Play, and Emotion Regulation (JASPER) interventions, has been found to be effective for promoting social communication in young children with autism (Kasari et al. in J Am Acad Child Adolesc Psychiatry 53(6):635-646, https://doi.org/10.1016/j.jaac.2014.01.019 , 2014). The current study examined the effects of this naturalistic intervention on social language use in three children with autism who were in the early stages of language acquisition. Generalization to communication partners who did not utilize the intervention strategies was systematically examined using a multiple-baseline design. The results from this study indicate that this blended intervention is effective in increasing target social language for young children with autism, however, generalization to communication partners does not readily occur. Implications for practice and future research are discussed.


cFLIP protein prevents tumor necrosis factor-alpha-mediated induction of caspase-8-dependent apoptosis in insulin-secreting betaTc-Tet cells.
Type 1 diabetes is characterized by the infiltration of activated leukocytes within the pancreatic islets, leading to beta-cell dysfunction and destruction. The exact role played by interferon-gamma, tumor necrosis factor (TNF)-alpha, and interleukin-1beta in this pathogenic process is still only partially understood. To study cytokine action at the cellular level, we are working with the highly differentiated insulin-secreting cell line, betaTc-Tet. We previously reported that it was susceptible to apoptosis induced by TNF-alpha, in combination with interleukin-1beta and interferon-gamma. Here, we report that cytokine-induced apoptosis was correlated with the activation of caspase-8. We show that in betaTc-Tet cells, overexpression of cFLIP, the cellular FLICE (FADD-like IL-1beta-converting enzyme)-inhibitory protein, completely abolished cytokine-dependent activation of caspase-8 and protected the cells against apoptosis. Furthermore, cFLIP overexpression increased the basal and interleukin-1beta-mediated transcriptional activity of nuclear factor (NF)-kappaB, whereas it did not change cytokine-induced inducible nitric oxide synthase gene transcription and nitric oxide secretion. The presence of cFLIP prevented the weak TNF-alpha-induced reduction in cellular insulin content and secretion; however, it did not prevent the decrease in glucose-stimulated insulin secretion induced by the combined cytokines, in agreement with our previous data demonstrating that interferon-gamma alone could induce these beta-cell dysfunctions. Together, our data demonstrate that overexpression of cFLIP protects mouse beta-cells against TNF-alpha-induced caspase-8 activation and apoptosis and is correlated with enhanced NF-kappaB transcriptional activity, suggesting that cFLIP may have an impact on the outcome of death receptor-triggered responses by directing the intracellular signals from beta-cell death to beta-cell survival.


Study of HSV-1 DNA species from trigeminal ganglia of rabbits during acute and latent infections.
Recurrent herpetic keratitis remains a major cause of corneal blindness in developed countries. A fundamental unanswered question regarding herpes simplex virus infection concerns the relationship between the virus and host cell DNA during latency. In the present study DNA was extracted from trigeminal ganglia during both acute and latent infection following ocular inoculation. Extracted, purified DNA was utilized for transfection and for hybridization studies using a 32P-labeled HSV-1 DNA probe. DNA extracted during acute infection was complete, linear and non-integrated. Autoradiographic patterns of DNA isolated during latent infection were suggestive of two separate DNA species.


Virulence of Escherichia coli in relation to host factors in women with symptomatic urinary tract infection.
The relationship between bacterial characteristics and the severity of urinary tract infection in adults has not been clarified. In this study, Escherichia coli strains (n = 178) were prospectively collected from women with community-acquired urinary tract infection. The isolates were identified by O:K:H serotype and characterized for adherence, hemolysin production, and serum bactericidal resistance. The patients had acute pyelonephritis with or without complicating factors and acute cystitis. Nine serotypes (O1:K1:H7, O1:K1:H-, O2:K1:H-, O4:K12:H1, O7:K1:H-, O9:K34:H-, O16:K1:H6, O16:K1:H-, and O75:K5:H-) comprised 65% of the strains in uncomplicated pyelonephritis, but were significantly less often encountered in complicated pyelonephritis or cystitis. Adherence was the single property most characteristic of the pyelonephritogenic clones. Adhesins specifically recognizing Gal alpha 1----4Gal beta-containing receptors occurred in 80% of strains in uncomplicated pyelonephritis, in 50% of strains in complicated infections, and in 37% of cystitis strains. Hemolysin production and serum resistance did not correlate with any disease pattern. Advanced age did not seem to reduce the selection of virulent E. coli to cause pyelonephritis. These results demonstrate in women a relationship between E. coli virulence and the severity of urinary tract infection analogous to that previously observed in pediatric populations and also illustrate the balance between host resistance and bacterial virulence in the urinary tract.


Numerical study of dc-biased ac-electrokinetic flow over symmetrical electrodes.
This paper presents a numerical study of DC-biased AC-electrokinetic (DC-biased ACEK) flow over a pair of symmetrical electrodes. The flow mechanism is based on a transverse conductivity gradient created through incipient Faradaic reactions occurring at the electrodes when a DC-bias is applied. The DC biased AC electric field acting on this gradient generates a fluid flow in the form of vortexes. To understand more in depth the DC-biased ACEK flow mechanism, a phenomenological model is developed to study the effects of voltage, conductivity ratio, channel width, depth, and aspect ratio on the induced flow characteristics. It was found that flow velocity on the order of mm/s can be produced at higher voltage and conductivity ratio. Such rapid flow velocity is one of the highest reported in microsystems technology using electrokinetics.


Regulation of capacitative calcium entries by alpha1-syntrophin: association of TRPC1 with dystrophin complex and the PDZ domain of alpha1-syntrophin.
Calcium mishandling in Duchenne dystrophic muscle suggested that dystrophin, a membrane-associated cytoskeleton protein, might regulate calcium signaling cascade such as calcium influx pathway. It was previously shown that abnormal calcium entries involve uncontrolled stretch-activated currents and store-operated Ca2+ currents supported by TRPC1 channels. Moreover, our recent work demonstrated that reintroduction of minidystrophin in dystrophic myotubes restores normal capacitative calcium entries (CCEs). However, until now, no molecular link between the dystrophin complex and calcium entry channels has been described. This study is the first to show by coimmunoprecipitation assays the molecular association of TRPC1 with dystrophin and alpha1-syntrophin in muscle cells. TRPC1 was also associated with alpha1-syntrophin in dystrophic muscle cells independently of dystrophin. Furthermore, glutathione S-transferase (GST) pull-down assays showed that TRPC1 binds to the alpha1-syntrophin PDZ domain. Transfected recombinant alpha1-syntrophin formed a complex with TRPC1 channels and restored normal CCEs in dystrophic muscle cells. We suggest that normal regulation of CCEs in skeletal muscle depends on the association between TRPC1 channels and alpha1-syntrophin that may anchor the store-operated channels to the dystrophin-associated protein complex (DAPC). The loss of this molecular association could participate in the calcium alterations observed in dystrophic muscle cells. This study provides a new model for the regulation of calcium influx by interaction with the scaffold of the DAPC in muscle cells.


A slice geometry phantom for cross sectional tomographic imagers.
This investigation presents the design and fabrication of a magnetic resonance imaging (MRI) test phantom for determining slice thickness, slice adjacency, slice offset, and slice angulation. This test phantom is a three-dimensional conic section of MRI image producing material; proper orientation allows analysis in each of the major imaging planes. The phantom design (geometrical configuration) incorporates both theoretical and quantitative methodologies. The necessary mathematical analyses are both simple and rapid. In addition, this phantom has been successfully used to assess the image slice parameters for computed tomography (CT) scanners and single photon emission computed tomography (SPECT) imaging systems. Slice profile parameter results, full width at half maximum (FWHM), from this phantom design are compared with conventional methods.


Mastoid findings secondary to posterior fossa dural venous sinus thrombosis.
In the setting of posterior fossa dural venous sinus thrombosis, mastoid findings can potentially be mistaken as the cause rather than a secondary effect. Obstruction of the mastoid venous drainage can lead to transudation of fluid into the mastoid air cells. We hypothesize that a continuum of the mastoid manifestations secondary to dural venous sinus thrombosis can be seen on MRI and that the difference in venous drainage between the mastoid and middle ears can assist with this important imaging differential. A retrospective review of acute dural venous sinus thrombosis cases and their follow-up imaging were graded as follows: no involvement; grade 1 mucosal congestion; grade 2, film of fluid; or grade 3, complete opacification. Presence of middle ear fluid was also documented. Of 22 posterior fossa dural venous sinus thrombosis cases without clinical infectious mastoiditis, 19 had mastoid findings: eight with grade 1, eight with grade 2, and three with grade 3. Middle ear fluid was seen in only one case. There was a statistically significant association between posterior fossa dural venous sinus thrombosis and mastoid findings (chisquare test (n = 22), p < 0.04). Fifteen of 18 cases with follow-up MRI examinations showed lessening of the mastoid findings with resolving dural venous sinus thrombosis. Acute posterior fossa dural venous sinus thrombosis may present with a spectrum of mastoid findings that should not be misdiagnosed as the cause of the thrombosis. This study illustrates that in the absence of clinical findings of mastoiditis, mastoid fluid with a clear middle ear argues that the mastoid changes are the effect of the dural venous sinus thrombosis rather than the cause.


Motivations for the recreational use of erectile enhancing medications in urban gay and bisexual men.
Recreational erectile enhancing medication (EEM) use has been associated with a number of health risk behaviours among gay and bisexual men. This study aims to extend previous findings about the associations between recent EEM use and illegal drug use, incident sexually transmitted infections (STIs) and unprotected sex, as well as to report on motivations for EEM use. A cross-sectional, street-intercept survey method was used to collect data from 912 gay/bisexual men at two large lesbian, gay and bisexual community events in New York City in 2006. Lifetime EEM use was reported by 28.0% of the men; 17.4% used EEM in the past 3 months. EEM users were more likely to be white and HIV positive. EEM users were more likely to engage in unprotected anal insertive sex with seroconcordant and serodiscordant partners. EEM users who were HIV negative were more likely to report using alcohol and other drugs before and during sex, especially crystal methamphetamine (AOR 18.66; 95% CI 6.82 to 51.02) as well as to endorse incident STIs. The most frequent responses for EEM use were to "add to the fun", "maintain an erection while using a condom" and "to have sex for hours". Men with HIV were 2.93 times (95% CI 1.24 to 6.88) more likely to endorse using EEMs to bareback. Gay and bisexual men use EEMs to enhance their sexual experiences among other motives. Different motives and correlates emerged by HIV status. Overall, EEM use was correlated with multiple health risk behaviours. EEM users who were HIV negative appear to be at particularly high risk of acquiring HIV.


BRONCHIECTASIS IN ADULT PATIENTS: CLINICAL PECULIARITIES AND APPROACHES TO THE TREATMENT.
The aim: To perform a clinical analysis of bronchiectasis in adults, to analyze the effectiveness of nebulizer therapy with hypertonic NaCl solution with hyaluronic acid. Materials and methods: All patients were performed clinical-functional examination (MRC dyspnea index, Sp O2, 6-minute walking test, external respiration function); calculated the index BODE, analyzed the SGRQ, studied the results of sputum. Statistical data analysis was performed using the Microsoft Excel for Microsoft 365 MSO 16.0.13530.2040418 package of statistical functions. Results: The main symptom in 100% of cases was chronic cough with production of sputum. Patients were concerned about shortness of breath (91.7%), episodic hemoptysis (29.2%), systemic symptoms (fatigue, weight loss). Hypertonic NaCl solution has a direct mucolytic effect, osmotic and anti-edematous effect. Protection of the mucous membrane of the respiratory tract makes hyaluronic acid an ideal additional component of hypertonic saline solution. All patients showed a positive effect of treatment immediately. After 2 weeks, the respiratory rate decreased, the FEV1 index increased at 8.6 (p<0.05), SpO2 increased up to 93.75 ± 7.13%, the number of points according to the SGRQ decreased, BODE index also decreased. Conclusions: Leading clinical signs of bronchiectasis were: a chronic cough with daily sputum production (100% of patients), shortness of breath (91.7%). The use of nebulizer inhalations decreased shortness of breath at 17.6% (р<0.05), improved external respiratory function indices (FVCL increased at 9.7% (р<0.01), FEV1 at 8.6% (р<0.01)) and blood oxygen saturation increased at 4.9% (р<0.05)). The offered complex increased tolerance to physical exertion (the 6-minute walk test and 4-year survival (BODE prognostic index).


Loss of benzaldehyde in the fragmentation of protonated benzoylamines: Benzoyl cation as a hydride acceptor in the gas phase.
In electrospray ionization tandem mass spectrometry of protonated 1-benzoylamines (1-benzoylpiperadine, 1-benzoylmorpholine, and 1-benzoyl-4-methylpiperazine), the dominant fragmentation pathway was amide bond cleavage to form benzoyl cation and neutral amine. Meanwhile, in their fragmentations, an interesting loss of benzaldehyde (106 Da) was observed and identified to derive from hydride transfer reaction between the benzoyl cation and amine. A stepwise mechanism for loss of 106 Da (benzene and CO) could be excluded with the aid of deuterium labeling experiment. Theoretical calculations indicated that hydride transfers from amines (piperadine, morpholine, and 1-methylpiperazine) to benzoyl cation were thermodynamically permitted, and 1-methylpiperazine was the best hydride donor among the 3 amines. The mass spectrometric experimental results were consistent with the computational results. The relative abundance of the iminium cation (relative to the benzoyl cation) in the fragmentation of protonated 1-benzoyl-4-methylpiperazine was higher than that in the fragmentation of the other 2 protonated 1-benzoylamines. By comparing the fragmentations of protonated 1-benzyl-4-methylpiperazine and protonated 1-benzoyl-4-methylpiperazine and the energetics of their hydride transfer reactions, this study revealed that benzoyl cation was a hydride acceptor in the gas phase, but which was weaker than benzyl cation.


CD44 and VEGF expression in extrahepatic metastasis of human hepatocellular carcinoma.
We investigated the correlation between vascular endothelial growth factor (VEGF) and CD44 expression in hepatocellular carcinoma (HCC) and the frequency of extrahepatic metastasis, in order to evaluate the influence of vascular growth and adhesion molecules in facilitation of distant metastasis. We obtained materials from primary lesions of HCC with no extrahepatic metastasis (control group) and primary lesions and metastatic lesions with extrahepatic metastasis (metastasis group). Immunohistochemical staining was performed using anti-human CD44v3 monoclonal antibodies and anti-human VEGF ab-3 monoclonal antibodies. Although pathological parameters such as tumor size, differentiation, capsule formation, and vascular invasion were analyzed, there was no marked difference among the groups. Percentages of nodules with VEGF-positive tumor and sinusoidal cells were low in primary lesions of the control and metastasis groups, while high in metastatic lesions in the metastasis group. On the other hand, percentages of nodules with CD44-positive tumor and sinusoidal cells were low in primary lesions of the control group, while high in primary lesions and metastatic lesions of the metastasis group. The present study demonstrated that CD44 expression in primary lesions is related to a higher frequency of extrahepatic metastasis, suggesting that this is a clinicopathologically useful parameter in predicting the occurrence of distant metastasis.


The cost of alkaline solutions in ambulatory hemodialysis: an analysis about wasteful from the processes control.
There are few studies about costs of inputs used in hemodialysis and among these expenditures, the compounds that make up the dialysate are one of the values considered as representative of this therapy. However, there aren't costs studies that guiding solutions. The objective of this article is discuss whether there is wasteful of alkaline solutions in ambulatory hemodialysis and hence the possibility of reduction in cost from the standardization process simulation of establishment of dialysate flow in periods between shifts in hemodialysis outpatients. Starting from an observational analytic, a simulation was performed twenty case scenarios, which ten cases established by standardizing processes control on the dialysate flow in recession. The combination of data was performed using as a basis the prices of three suppliers of alkali liquid or powder. It was observed among the scenarios with standardized processes, ranging between 7.7% and 33.3% savings in the alkaline solution cost (powder or liquid), by reducing waste. It is possible to restrain the wasteful use of alkaline solutions, both powder and liquid. Consequently, its cost from the patterning on reducing the flow of dialysate during the intervals between shifts observed in the outpatient hemodialysis. However, these results are conditional upon the commitment of health professionals, mainly to supervision exercise and control of activities in quality function deployment.


ELISA assay for measurement of human hemoglobin A and hemoglobin F.
An enzyme-linked immunosorbent assay (ELISA) for the measurement of nanogram quantities of hemoglobin A and hemoglobin F is described. The assay employs hemoglobin bound to polystyrene test tubes. The antigen is quantitated by the addition of rabbit antibody specific for the hemoglobin type, followed by a second antibody of goat antirabbit gamma globulin coupled to alkaline phosphatase. Quantitation of the reaction is achieved by incubating the coated tubes with p-nitrophenyl phosphate. The binding characteristics, the linearity, the ability of the assay to discriminate between hemoglobin A and hemoglobin F, the ability to discriminate between native and denatured gamma globin, and the comparison of this assay with a previously described immunoradiometric (IRMA) assay are discussed.


[Drosophila melanogaster imaginal discs mitotic anomalies induced by tumor-supressor dlg silencing construction].
Mitosis, cytokinesis and nuclear texture of wing imaginal discs cells silenced by UAS-RNAi-dlg construct induced by 1096-Ga 14 driver were studied. The silencing construct contains coding region of dlg gene and the complementary region. Further, this RNA hairpin (Dietzl et al., 2007) is processed by endogenous protein Dicer and the resulting RNA fragments silence mRNA dlg. Tumor suppressor gene dlg is encoding for 21 transcripts. The construct UAS-RNAi-dlg inactivates 14 transcripts--RE, RH, RQ, RS, RG, RD, RL, RB, RK, RR, RT, RN, RA, RP--and does not silenced the other 7 (RO, RF, RI, RU, RJ, RC, RM). This permits to study functions of proteins containg guanilate-kinase domain IPR008145 at C-end of the protein. The most important consequences of the silencing are abnormal mitotic exit and the formation of binuclear cells. Quantitative fluorescence measurements of anti-H3-p histone and DAPI signals showed phase-specific changes in nuclear texture. The inactivation of cellular cortex polarization is the most likely target of dlg inactivation in mitosis.


Calcium-dependent chloride transient currents in the immature oocyte of the frog, Rana esculenta.
Transient currents of chloride were studied in the plasma membrane of immature frog oocyte in voltage clamp conditions. The transients appeared to be activated by an influx of Ca2+ from the external medium. The mechanism leading to a surge of intracellular Ca2+ concentration needed at least 30 sec before full recovery. It was inhibited by substituting Ba2+ for Ca2+ in the external medium, or in the presence of La3+, Co2+ and Cd2+, or when external Na+ was replaced by Li+. Verapamil proved ineffective. The data suggest that an intracellular system of Ca-activated Ca-release is present in the frog oocyte, which can be primarily activated by membrane hyperpolarization via an influx of Ca2+ through non-selective channels.


Cell-by-cell reconstruction in reaggregates from neonatal gerbil retina begins from the inner retina and is promoted by retinal pigmented epithelium.
For future retinal tissue engineering, it is essential to understand formation of retinal tissue in a 'cell-by-cell' manner, as can be best studied in retinal reaggregates. In avians, complete laminar spheres can be produced, with ganglion cells internally and photoreceptors at the surface; a similar degree of retinal reconstruction has not been achieved for mammals. Here, we have studied self-organizing potencies of retinal cells from neonatal gerbil retinae to form histotypic spheroids up to 15 days in culture (R-spheres). Shortly after reaggregation, a first sign of tissue organization was detected by use of an amacrine cell (AC)-specific calretinin (CR) antibody. These cells sorted out into small clusters and sent unipolar processes towards the centre of each cluster. Thereby, inner cell-free spaces developed into inner plexiform layer (IPL)-like areas with extended parallel CR(+) fibres. Occasionally, IPL areas merged to combine an 'inner half retina', whereby ganglion cells (GCs) occupied the outer sphere surface. This tendency was much improved in the presence of supernatants from retinal pigmented cells (RPE-spheres), e.g. cell organization and proliferation was much increased, and cell death shortened. As shown by several markers, a perfect outer ring was formed by GCs and displaced ACs, followed by a distinct IPL and 1-2 rows of ACs internally. The inner core of RPE spheres consisted of horizontal and possibly bipolar cells, while immunostaining and RT-PCR analysis proved that photoreceptors were absent. This shows that (1) mammalian retinal histogenesis in reaggregates can be brought to a hitherto unknown high level, (2) retinal tissue self-organizes from the level of the IPL, and (3) RPE factors promote formation of almost complete retinal spheres, however, their polarity was opposite to that found in respective avian spheroids.


Chondroid lipoma--a case report.
Chondroid lipoma is a rare fatty tumor of soft tissues, especially in limbs and limb girdles. Though it is clinically benign, the main importance lies in its histological similarity with myxoid liposarcoma and chondrosarcoma, which have poorer prognosis. In our study, classical histological pattern of chondroid lipoma was confirmed on H&E and PAS stains with low mitotic count.


Biofeedback treatment of bladder dysfunction in multiple sclerosis. A randomized trial.
Fifteen women and five men with bladder dysfunction due to multiple sclerosis were randomized to plus/minus biofeedback using bladder pressure and simultaneous EMG registration via surface electrodes. All the patients had behavioural modification, pharmacological adjustment and pelvis floor training. The number of incontinence episodes decreased and maximal cystometric capacity increased, while first sensation and pad test were unchanged. Subjective treatment results assessed by visual analogue scales for incontinence and obstrusive voiding symptoms were highly significant. However no biofeedback parameter was improved and no difference could be demonstrated between the two treatment groups. In conclusion the used biofeedback technique is insufficient and the 60 min. standardized pad weighing test is inadequate in this type of patients.


A FISCHER INDOLIZATION STRATEGY TOWARD THE TOTAL SYNTHESIS OF (-)-GONIOMITINE.
A Fischer indolization strategy toward the core of (-)-goniomitine is reported. Initial investigations into the Pd-catalyzed asymmetric allylic alkylation of dihydropyrido[1,2-a]indolone (DHPI) substrates are also discussed.


[Evaluation of the treatment of chronic active hepatitis (HBsAg+) with isoprinosine. II. Immunological studies].
A two-month treatment of the chronic active hepatitis (HBsAg+) with isoprinosine produced quantitative and functional T-cells populations in patients with cellular response disorders. Immunological studies have shown that such an effect of isoprinosine lasted for about 4-5 months. Repeated administration of isoprinosine for one month normalized recurrent abnormalities in the monitored immunological parameters.


Analysis of 30 anaesthesia-related deaths in Germany between 2006 and 2015: An analysis of a closed claims database.
Anaesthesiology is one of the safest fields in medicine today in relation to mortality. Deaths directly because of anaesthesia have fortunately now become rare exceptions. Nevertheless, important findings can still be drawn from the rare deaths that still occur. The aim of this study was to identify and analyse the causes of deaths related to anaesthesia alone over a 10-year period. Retrospective structured analysis of a database of medical liability claims. Hospitals at all levels of care in Germany. The database of a large insurance broker included data for 81 413 completed liability claims over the 10-year period from 2006 to 2015. Among 1914 cases associated with anaesthetic procedures, 56 deaths were identified. Of these, 30 clearly involved anaesthesia (Edwards category 1) and were included in the evaluation. None (retrospective database analysis). Causes of anaesthesia-related death identified from medical records, court records, expert opinions and autopsy reports. The 30 deaths were analysed in detail at the case and document level. They included high proportions of 'potentially avoidable' deaths, at 86.6%, and what are termed 'never events', at 66.7%. Problems with the airway were the cause in 40% and problems with correct monitoring in 20%. In addition, communication problems were identified as a 'human factor' in 50% of the cases. The majority of the anaesthesia-related deaths investigated could very probably have been avoided with simple anaesthesiological measures if routine guidelines had been followed and current standards observed. Actions to be taken are inferred from these results, and recommendations are made. In future, greater care must be taken to ensure that the level of safety already achieved in anaesthesiology can be maintained despite demographic developments and increasing economic pressures.


The involvement of type 1a angiotensin II receptors in the regulation of airway inflammation in a murine model of allergic asthma.
There has been increasing evidence suggesting the involvement of angiotensin II (Ang II) and type 1 Ang II receptors (AT1) in the pathogenesis of bronchial asthma. However, whether such an involvement would promote or suppress the pathophysiology of asthma is controversial. The aim of this study was to investigate the role of AT1 in the development of allergic airway inflammation. Agtr1a+/+ [wild-type C57BL/6 mice (WT)] and Agtr1a-/- mice [AT1a knockout mice (AT1aKO)] with a genetic background of C57BL/6 were systemically sensitized to ovalbumin (OVA), followed by OVA inhalation. OVA-specific IgE in serum obtained just before the inhalation was measured. Bronchoalveolar lavage (BAL) fluid and lung tissues were obtained at various time-points. Cell numbers and differentiation, and cytokine contents in BAL fluids were determined. Peribronchial accumulation of eosinophils and mucus inclusions in the bronchial epithelium were evaluated in lung tissues stained histochemically. Cell numbers and differentiation in BAL fluids of the mice were also determined after lipopolysaccharide (LPS) inhalation. The levels of OVA-specific IgE in AT1aKO were significantly higher than those in WT. The numbers of total cell, eosinophils and lymphocytes in BAL fluids 7 days after OVA inhalation in AT1aKO were significantly higher than those in WT. Airway inflammation in bronchial tissues in terms of eosinophil accumulation and mucus hypersecretion in AT1aKO was also stronger than in WT. The contents of IL-4, IL-5 and IL-13, but not IFN-gamma, in BAL fluids of AT1aKO were significantly higher than those of WT. In contrast, neutrophil accumulation in BAL fluids after LPS inhalation was significantly higher in WT than in AT1aKO. AT1a might be involved in the negative regulation of the development of allergic airway inflammation through polarizing the T-helper (Th) balance towards Th1 predominance. Therefore, it would be of clinical importance to investigate the effects of long-term administration of AT1 blockers on the Th1/Th2 balance in hypertensive patients with bronchial asthma.


Oesophageal flap valvuloplasty and wrapping suturing prevent gastrooesophageal reflux disease in dogs after oesophageal anastomosis.
To examine the efficiency of oesophageal flap valvuloplasty and wrapping suturing technique in decreasing the rate of postoperative gastrooesophageal reflux disease in a dog model. We operated on 10 dogs in this study. First, we resected a 5-cm portion of the distal oesophagus and then restored the continuity of the oesophageal and gastric walls by end-to-end anastomosis. A group of five dogs was subjected to the oesophageal flap valvuloplasty and wrapping suturing technique, whereas another group (control) of five dogs was subjected to the stapling technique after oesophagectomy. The symptom of gastrooesophageal reflux was recorded by 24-h pH oesophageal monitoring. Endoscopy and barium swallow examination were performed on all dogs. Anastomotic leakage was observed by X-ray imaging, whereas benign anastomotic stricture and mucosal damage were observed by endoscopy. None of the 10 dogs experienced anastomotic leakage after oesophagectomy. Four dogs in the new technology group resumed regular feeding, whereas only two of the dogs in the control group tolerated solid food intake. pH monitoring demonstrated that 25% of the dogs in the experimental group exhibited reflux and that none had mucosal damage consistent with reflux. Conversely, both reflux and mucosal damage were observed in all dogs in the control group. The oesophageal flap valvuloplasty and wrapping suturing technique can improve the postoperative quality of life through the long-term elimination of reflux oesophagitis and decreased stricture formation after primary oesophageal anastomosis.


Regulation of pro-inflammatory cytokine expression by curcumin in hyaline membrane disease (HMD).
Persistent expression of pro-inflammatory cytokines is believed to play a major role in the pathogenesis of chronic lung disease (CLD) in premature infants. Inhibition of pro-inflammatory cytokine production in the lungs of preterm newborns may result in the attenuation of CLD. Curcumin is a naturally occurring phenolic compound derived from the food spice tumeric with broad based in vitro anti-inflammatory properties. In this study lung inflammatory cells from preterm newborns at risk for the development of CLD were derived via modified broncho-alveolar lavage and stimulated ex vivo with lipopolysaccharide (LPS) (10 ng/ml). Curcumin was added to these cultures at 0, 0.5 and 20 uM concentrations. Pro-inflammatory cytokine, TNFalpha, IL-1beta and IL-8 protein was measured from the culture supernatants 12 hours post culture. For control, adult peripheral blood mononuclear cells (PBMC) were cultured under the same conditions. Both neonatal lung inflammatory cells and adult PBMC produced high levels of pro-inflammatory cytokines in response to LPS. Curcumin produced significant inhibition of IL-1beta and IL-8 but minimal inhibition of TNFalpha expression by preterm lung inflammatory cells at 20 uM concentrations. Adult PBMC expression of IL-8 was significantly inhibited by curcumin at 20 uM concentrations. Therefore, curcumin inhibits pro-inflammatory cytokine production (TNFalpha, IL-1beta and IL-8) by lung inflammatory cells ex vivo. Pathways involved with curcumin regulation of these cytokines are developmentally intact and functional in premature infants. Curcumin may be effective as a therapeutic agent in the attenuation of CLD.


Design and evaluation of artificial receptors for the reversal of neuromuscular block.
Applying patient friendly and cost-efficient medications in healthcare will be a real challenge in the 21st century. Sugammadex is a selective, yet expensive agent used for the post-surgical reversal of neuromuscular block since 2008. A wide library of cyclodextrin-based follow-ups, having potentially similar affinity towards target aminosteroid type neuromuscular blocking agents has been established. Almost 20 compounds were assessed with respect to in vitro affinity against three commonly applied drugs. Based on the capillary electrophoretic screening, carboxymethylated and sulfobutylated gamma-cyclodextrin derivatives have the potential to be promising lead molecules for their affinity towards pipecuronium was identical or even superior to Sugammadex. Carboxymethylated gamma-cyclodextrin showed efficient and complete reversal of the pipecuronium induced neuromuscular block in an ex vivo rat diaphragm experiment.


Phase I pharmacotoxicology study of human fibroblast interferon in human cancers.
Twelve patients with advanced cancer were treated with human fibroblast interferon. Interferon administered im in doses up to 10 x 10(6) U three times weekly for 2 weeks was associated with highly variable, but detectable, plasma levels. Bolus interferon given iv was associated with a reproducible, immediate peak of activity followed by a rapid loss of detectable activity. Continuous infusion of interferon over 2 hours resulted in a slowly increasing dose-related level to a maximum near the end of the infusion followed by a loss of detectable activity for about 1 hour following infusion. Interferon administered both im and iv caused a mild, easily tolerated pyrexia as the only regularly occurring side effect. In 1 patient interferon treatment suppressed a malignant clone of circulating blasts trisomic for chromosomes No. 8 and 21 from 59 to 0%.


Methylation of WNT target genes AXIN2 and DKK1 as robust biomarkers for recurrence prediction in stage II colon cancer.
Stage II colon cancer (CC) still remains a clinical challenge with patient stratification for adjuvant therapy (AT) largely relying on clinical parameters. Prognostic biomarkers are urgently needed for better stratification. Previously, we have shown that WNT target genes AXIN2, DKK1, APCDD1, ASCL2 and LGR5 are silenced by DNA methylation and could serve as prognostic markers in stage II CC patients using methylation-specific PCR. Here, we have extended our discovery cohort AMC90-AJCC-II (N=65) and methylation was analyzed by quantitative pyrosequencing. Subsequently, we validated the results in an independent EPICOLON1 CC cohort (N=79). Methylation of WNT target genes is negatively correlated to mRNA expression. A combination of AXIN2 and DKK1 methylation significantly predicted recurrences in univariate (area under the curve (AUC)=0.83, confidence interval (CI): 0.72-0.94, P<0.0001) analysis in stage II microsatellite stable (MSS) CC patients. This two marker combination showed an AUC of 0.80 (CI: 0.68-0.91, P<0.0001) in the EPICOLON1 validation cohort. Multivariate analysis in the Academic Medical Center (AMC) cohort revealed that both WNT target gene methylation and consensus molecular subtype 4 (CMS4) are significantly associated with poor recurrence-free survival (hazard ratio (HR)methylation: 3.84, 95% CI: 1.14-12.43; HRCMS4: 3.73, 95% CI: 1.22-11.48). CMS4 subtype tumors with WNT target methylation showed worse prognosis. Combining WNT target gene methylation and CMS4 subtype lead to an AUC of 0.89 (0.791-0.982, P<0.0001) for recurrence prediction. Notably, we observed that methylation of DKK1 is high in BRAF mutant and CIMP (CpG island methylator phenotype)-positive cancers, whereas AXIN2 methylation appears to be associated with CMS4. Methylation of AXIN2 and DKK1 were found to be robust markers for recurrence prediction in stage II MSS CC patients. Further validation of these findings in a randomized and prospective manner could pave a way to identify poor prognosis patients of stage II CC for AT.


Serum Neurofilament Light Chain Levels Are Associated with Clinical Characteristics and Outcome in Patients with Cervical Artery Dissection.
Serum neurofilament light chain (sNfL) levels represent a promising marker of neuroaxonal injury. They are elevated in several neurological conditions, but their importance in cerebrovascular diseases remains unclear. In a proof of concept study, we compared sNfL levels with clinical characteristics and outcome in patients with cervical artery dissection (CeAD). A total of 49 non-traumatic CeAD patients were included. sNfL levels were measured by high-sensitivity electrochemiluminescence immunoassay. Levels were compared with regard to (i) type of presenting symptoms (local symptoms only (n = 8), transient ischemic attack (TIA; n = 10) or ischemic stroke (n = 31)), (ii) stroke severity quantified by National Institute of Health Stroke Scale (NIHSS), (iii) time interval between onset of symptoms and blood sampling and (iv) 3-month outcome as measured by the modified Rankin Scale score. Analyses were performed using univariate and multivariate linear and ordinal regression models. CeAD patients presenting with stroke had significantly higher sNfL levels (median 108.9 pg/ml, interquartile range (37.8-427.7)) than patients with TIA (16.4 pg/ml (8.7-36.3), p = 0.002) or local symptoms (23.4 pg/ml (17.8-30.8), p = 0.0007). Among stroke patients, sNfL levels were positively associated with both NIHSS (p = 0.0002) and time between stroke onset and serum sampling (p = 1.9 × 10-6). Higher sNfL levels were associated with unfavorable outcome at 3 months (OR 4.67, 95% CI 1.69-12.95, p = 0.003). However, this association lost significance after adjustment for NIHSS. The highest sNfL level was observed in a TIA patient who had ischemic stroke 1 day after serum sampling for sNfL measurement. sNfL levels were increased in CeAD patients presenting with stroke, correlated with clinical severity and were influenced by the time point of blood sampling. The prognostic meaning of sNfL in CeAD deserves further testing.


Prevalence, pattern & correlates of hypertension among tribal population of Kashmir, India: A cross-sectional study.
The prevalence of hypertension is increasing among all ethnic groups across the globe with only a handful of studies from India addressing the prevalence of hypertension among tribal population. In view of paucity of data, this study was aimed at estimating the prevalence of hypertension and associated risk factors among tribal population of Kashmir, India. This cross-sectional survey included 6808 tribals aged >20 yr (5695 Gujjars and 1113 Bakarwals) from five randomly selected districts of Kashmir. Modified WHO-STEPS surveillance questionnaire was used to collect relevant data. Hypertension was defined by Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension (JNC 8) criteria. The mean age of our study participants was 43.12 ± 15.69 years. Overall prevalence of hypertension [95% confidence interval (CI)] was 41.4% (39.9-42.9%) [men=46.7% (44.1-49.1%); women=37.9% (35.9-39.9%)]. The prevalence of prehypertension (95% CI) in our study was 35 per cent (33.7-36.6%). Higher age [adjusted odds ratio (OR) (95% CI): >70 yr-2.2 (1.9-2.4)], passive smoking [OR-1.3 (1.1-1.5)], family history of hypertension [OR-1.6 (1.4-1.7)] and obesity [OR-1.3 (1.1-1.6)] were significantly associated with hypertension. A weak positive correlation was observed between BP (systolic/diastolic) with haemoglobin, red blood cell count and haematocrit (P<0.05). Gujjar and Bakarwal tribes of Jammu and Kashmir showed high prevalence of hypertension. Hence, urgent policies and reforms are needed to tackle this silent epidemic and further studies focusing on community-based interventions are required.


An extraordinarily low diploid chromosome number in the reptile Gonatodes taniae (Squamata, Gekkonidae).
Mitotic and meiotic chromosomes of the gekkonid lizard Gonatodes tanieae from Venezuela were analyzed with conventional staining, differential banding techniques, and in situ hybridization using a synthetic telomeric DNA probe. The karyotype of this species is distinguished by the extraordinarily reduced diploid chromosome number of 2n = 16, which is the lowest value known for reptiles. In contrast to most other reptilian species, G. taniae has exclusively bi-armed (meta- and submetacentric) macrochromosomes and no microchromosomes. Examination of the mitotic chromosomes with AT and GC base pair-specific fluorochromes shows the absence of multiple banding patterns in euchromatic regions. The n = 8 diakinetic bivalents of male meiosis present terminal, subterminal, interstitial, and pericentromeric chiasmata. Comparison of the karyotypes of G. taniae and G. vittatus (also collected in Venezuela), and with those of three other Gonatodes species, indicates that the exceptional diploid number of 2n = 16 is the result of repeated centric fusions. In addition to the telomeres, all pericentromeric regions of the G. taniae chromosomes contain considerable amounts of the (TTAGGG)n telomeric sequence. These are probably not only relics of the centric fusions, but also a major component of the highly repetitive DNA in the C band-positive heterochromatin.


Prevalence of Depression in Older Nursing Home Residents in High and Low Altitude Regions: A Comparative Study.
Objective: Depressive symptoms (depression hereafter) is common in older adults, and closely associated with environmental factors. This study compared the prevalence of depression in older adults living in high-altitude and low-altitude regions, and their association with quality of life (QOL). Method: A total of 632 older nursing home residents were included, with 425 participants living in low-altitude and 207 participants living in high-altitude regions. Depression and QOL were assessed using standardized instruments. Results: The prevalence of depression was 26.9% (95% CI: 23.43-30.37%) in the whole sample of older nursing home residents, with 11.1% (95% CI: 8.01-14.05%) in those living in low-altitude and 59.4% (95% CI: 52.68-66.17%) in those living in high-altitude regions. Multiple logistic regression analysis revealed that living in low-altitude region (P < 0.001, OR = 0.07, 95% CI: 0.04-0.12) was associated with lower risk of depression, while perception of poor health status (P < 0.001, OR = 3.86, 95% CI: 1.98-7.54) and having insomnia (P < 0.001, OR = 4.76, 95% CI: 2.99-7.56) were associated with higher risk of depression. QOL was significantly lower in physical (F (1,632) = 35.421, P < 0.001), psychological (F (1,632) = 20.777, P < 0.001), social (F (1,632) = 8.169, P < 0.001) and environmental domains (F (1,632) = 11.861, P < 0.001) in those with depression. Conclusion: Depression was common in older nursing home residents especially those living in the high-altitude region. Considering the negative impact of depression on QOL and functional outcomes, routine screening and timely treatment of depression should be implemented in this population.


Submitting a research proposal for ethical approval.
1. Research involving human subjects should conform to ethical and moral codes. 2. Special considerations should apply in respect of research in special and vulnerable groups such as children, people with learning disabilities/mental handicap, psychiatric patients and prisoners. 3. Local research ethics committees should protect subjects of research from possible harm. 4. Local research ethics committees should exercise discretion as to the mode of consent appropriate to the nature of the proposed research.