Educational inequalities, urbanicity and levels of non-communicable diseases risk factors: evaluating trends in Argentina (2005-2013).
We investigated a) whether urbanicity is associated with individual-level non-communicable diseases (NCD) risk factors and whether urbanicity modifies trends over time in risk factors; and (b) whether educational inequalities in NCD risk factors change over time or are modified by province urbanicity. We used data from three large national surveys on NCD risk factors (Encuesta Nacional de Factores de Riesgo; ENFR2005-2009-2013) conducted in urban areas of Argentina (n = 108,489). We used gender-stratified logistic random-intercept models (individuals nested within provinces) to determine adjusted associations of self-reported individual NCD risk factors (hypertension, diabetes, obesity, and current smoking) with education and urbanicity. In both men and women, the prevalence of obesity and diabetes increased over time but smoking decreased. Hypertension prevalence increased over time in men. Higher urbanicity was associated with higher odds of smoking and lower odds of hypertension in women but was not associated with NCD risk factors in men. Obesity increased more over time in more compared to less urbanized provinces (in men) while smoking decreased more over time in less urbanized provinces. All risk factors had a higher prevalence in persons with lower education (stronger in women than in men), except for diabetes in men and smoking in women. Educational inequalities in obesity (in men) and hypertension (in men and women) became stronger over time, while an initial inverse social gradient in smoking for women reverted and became similar to other risk factors over time. In general, the inverse associations of education with the risk factors became stronger with increasing levels of province urbanicity. Increasing prevalence of diabetes and obesity over time and growing inequities by education highlight the need for policies aimed at reducing NCD risk factors among lower socioeconomic populations in urban environments in Argentina.


Unilateral Withdrawal of Life-sustaining Therapy in a Severely Impaired Child.
An infant with complex congenital heart disease suffers a prolonged cardiac arrest with minutes of anoxia. He is left with severe brain damage and profound neurologic impairment. He no longer responds to caregivers. Much of the time, he cries and grimaces as if in pain. He has required increasing sedation to control these symptoms. His parents live hours from the hospital and seldom visit. When their infant's situation is explained to them over the telephone, they request that doctors "do everything to keep him alive." His bedside caregivers report high levels of moral and psychological distress and frequently discuss J.S.'s "suffering." An ethics consultation is requested, asking whether it is permissible to withdraw life support despite the parents' request that therapy continue.


[Medullary sponge kidney (MSK) in association with glomerulonephritis (GNP)].
Medullary sponge kidney (MSK) is a congenital, non-hereditary anomaly characterized by dilation of the precalix ducts. It is often associated with other diseases, and its symptoms are linked to frequent complications, such as sepsis of the urinary system and the renal colic of nephrolithiasis. However, MSK is rare in association with glomerulonephritis (GNP), as can be seen from medical literature data that shows only one case (reported in 1974) in which MSK with a concomitant focal sclerosing glomerulonephritis was noted. In this report, we describe a case of MSK that was found after a routine renal echograph and biopsy of a mesangial GNP previously diagnosed at another center. The echographic results showing typical MSK was confirmed by means of RX urography and renal TC. The MSK-glomerulonephritis combination appears to be completely random, because the involved structures (the collecting duct and the glomerule) have different embryologic origin. Therefore, a pathogenic hypothesis common to the two anomalies seems rather unlikely. Although MSK is a usually benign disease, because a compromise of glomerular filtration that occurs in approximately 10% of cases, proper diagnosis is important to allow prophylactic intervention aimed at the reduction of complications that could reduce overall renal function when associated with other nephropathies. Renal echography is an important diagnostic tool that may reveal more cases of MSK than previously reported.


Ultrastructural localization of a platelet-derived growth factor/v-sis-related protein(s) in cytoplasm and nucleus of simian sarcoma virus-transformed cells.
The subcellular distribution of v-sis-related protein(s) was analyzed in three simian sarcoma virus (SSV)-transformed cell lines with immunofluorescence and protein A-gold labeling techniques using rabbit polyclonal anti-platelet-derived-growth factor (PDGF) antisera. Antigenically reactive proteins were recognized in subcellular organelles related to protein synthesis and processing, including polyribosomes, endoplasmic reticulum, and the Golgi apparatus, as well as on the cytoplasmic surface of plasma membranes. Prominent immunoreactive proteins were also shown in association with nuclear chromatin in intact cells and in isolated nuclei using Lowicryl K4M resin embedding techniques. Protein A-gold labeling was markedly reduced in sections of non-SSV-transformed fibroblasts incubated with anti-PDGF and absent from SSV-transformed cells if Epon resin was substituted for Lowicryl in the embedding process or if sections were with irrelevant antisera. Nuclear localization of v-sis-related antigens was confirmed in a nitrocellulose-based immunoassay using nuclei isolated from SSV-transformed fibroblasts. Thus, polypeptides recognized antigenically as related to the v-sis gene product not only may be found in subcellular organelles associated with protein synthesis and packaging but also may be found in the nucleus of SSV-transformed cells. These results raise the possibility that v-sis- or PDGF-like proteins may function within the nucleus of SSV-transformed cells.


Incidence of deep infection in aseptic revision THA using vancomycin-impregnated impacted bone allograft.
The addition of antibiotic to cement is a frequent practice in aseptic revision hip surgery There is concern about adding vancomycin to cement due to potential effects on mechanical properties and prolonged elution of subtherapeutic levels antibiotic. Bone allografts can store and provide high levels of vancomycin to surrounding tissues. We analyzed the incidence of infection after one-stage aseptic revision hip reconstruction utilizing acetabular and/or femoral vancomycin-impregnated impacted bone allograft and a THA fixed with cement containing no antibiotic. We hypothesized that the infection rate may be similar to that reported in the literature following traditional impaction grafting using antibiotic loaded cement. Seventy five consecutive patients (80 hips) with a preoperative Merle D'Aubigné and Postel functional score averaging 4.8 points were followed up for a mean of 36 months (range 24 - 59 months). The incidence of infection was 1.25% (CI 95%=96.26-100%). A deep infection (thought to be haematognous in origin) occurred in 1 patient 2 years after the index surgery. The average postoperative Merle D´Aubigne score was 16.2 points. The last radiographic evaluation demonstrated a less than 5 mm acetabular migration and a less than 5 mm femoral subsidence in all cases. Vancomycin-supplemented allografts restored bone stock and provided sound fixation with a low incidence of infection. This incidence of deep sepsis is similar to that reported with antibiotic-loaded PMMA but without the reported mechanical and pharmacological disadvantages.


Characteristics of Healthy Older Adults that Influence Self-rated Cognitive Function.
We sought to clarify the nature of self-reported cognitive function among healthy older adults by considering the short-term, within-person association (coupling) of subjective cognitive function with objective cognitive performance. We expected this within-person coupling to differ between persons as a function of self-perceived global cognitive decline and depression, anxiety, or neuroticism. This was an intensive measurement (short-term longitudinal) study of 29 older adult volunteers between the ages of 65 and 80 years without an existing diagnosis of dementia or mild cognitive impairment. Baseline assessment included neuropsychological testing and self-reported depression, anxiety, and neuroticism, as well as self- and informant-reported cognitive decline (relative to 10 years previously). Intensive within-person measurement occasions included subjective ratings of cognitive function paired with performance on a computerized working memory (n-back) task; each participant attended four or five assessments separated by intervals of at least one day. Statistical analysis was comprised of multilevel linear regression. Comparison of models suggested that both neuroticism and self-rated cognitive decline explained unique variance in the within-person, across-occasion coupling of subjective cognitive function with objective working memory performance. Self-ratings of cognition may accurately reflect day-to-day variations in objective cognitive performance among older adults, especially for individuals lower in neuroticism and higher in self-reported cognitive decline. Clinicians should consider these individual differences when determining the validity of complaints about perceived cognitive declines in the context of otherwise healthy aging. (JINS, 2018, 24, 57-66).


Diagnostic cutoff for pressure drop coefficient in relation to fractional flow reserve and coronary flow reserve: A patient-level analysis.
Functional assessment of intermediate coronary stenosis during cardiac catheterization is conducted using diagnostic parameters like fractional flow reserve (FFR), coronary flow reserve (CFR), hyperemic stenosis resistance index (HSR), and hyperemic microvascular resistance (HMR). CDP (ratio of pressure drop across a stenosis to distal dynamic pressure), a nondimensional index derived from fundamental fluid dynamic principles, based on a combination of intracoronary pressure, and flow measurements may improve the functional assessment of coronary lesion severity. Patient-level data pertaining to 350 intracoronary pressure and flow measurements across coronary stenoses was assessed to evaluate CFR, FFR, HSR, HMR, and CDP. CDP was calculated as (ΔP)/(0.5 × ρ × APV(2)). The density of blood (ρ) was assumed to be 1.05 g/cm(3). The correlation of current diagnostic parameters (CFR, FFR, HSR, and HMR) with CDP was evaluated. The receiver operating characteristic (ROC) curve was used to identify the optimal cut-off point of CDP, corresponding to the clinically used cut-off values (FFR = 0.80 and CFR = 2.0). CDP correlated significantly with FFR (r = 0.81, P < 0.05) and had significant diagnostic efficiency (ROC-area under curve of 86%), specificity (72%) and sensitivity (85%) at FFR < 0.8. The corresponding cut-off value for CDP to detect FFR < 0.8 was at CDP>25.4. CDP also correlated significantly (r = 0.98, P < 0.05) with epicardial-specific parameter, HSR. CDP, a functional parameter based on both intracoronary pressure and flow measurements, has close agreement (area under ROC curve = 86%) with FFR, the frequently used method of evaluating stenosis severity.


Elevated Hemoglobin and Macrocytosis: A Neglected Association to Become a Diagnostic Tool (A Case Report).
The landmark value of mean corpuscular volume (MCV) in the diagnosis and classification of anemias has been established more than a century ago. In contrast, the importance of MCV assessment in patients with elevated hemoglobin and hematocrit is not nearly as appreciated. This case describes a patient who exhibited long-standing macrocytosis (elevated MCV) that contributed to elevated hemoglobin and hematocrit levels thus mimicking a diagnosis of polycythemia vera. The case demonstrates that discounting the MCV effect on hemoglobin/hematocrit levels can lead to potential errors in interpretation of blood tests and misdiagnosis.


Association between dental pain, use of dental services and school absenteeism: 2015 National School Health Survey, Brazil.
To analyze association between dental pain, use of dental services and school absenteeism in Brazilian adolescents. This was a cross-sectional study with data from the National School Health Survey (PeNSE 2015). The study's dependent variable was school absenteeism due to health reasons in the last 12 months. Socioeconomic characteristics, dental pain and use of dental services were the independent variables evaluated. Logistic regression was used to estimate odds ratios (OR) and respective 95% confidence intervals (95%CI). Data on 102,072 schoolchildren were included. Absenteeism prevalence due to health reasons was 53.7% (95%CI 53.2;54.3). In the adjusted analysis, there was association between dental pain and school absenteeism (OR=1.35 - 95%CI 1.26;1.45), and an increase in absenteeism occurrence the greater the number of dental visits. The results suggest that dental pain and frequency of dental visits may be related to school absenteeism.


Safety evaluation of Elixir Paregorico in healthy volunteers: a phase I study.
A liquid alcoholic extract of Papaver somniferum named Elixir Paregorico is extensively used for diarrheal diseases in Brazil. Its increased popularity has brought concerns and fears over the safety of this herbal product. Given the lack of investigative clinical studies, in this regard, this study investigated whether Elixir Paregorico administration causes any noticeable toxic effects in healthy volunteers. In all, 28 middle-aged healthy male (n = 14) and female (n = 14) were enrolled. After screening and a washout period, eligible subjects received four oral doses per day of Elixir Paregorico (3 mL diluted in 30 mL of water) over a 10-day period. Altogether, all 28 participants completed the study. The results of hematological and biochemical tests performed pre and post-treatment were within the normal range. In both male and female volunteers, there were no statistical differences (P > 0.05) in the results of clinical and laboratory tests performed at screening, on 5th and 10th day visits, and at final assessment. Although mild adverse events were related, which subsided spontaneously, no serious untoward reactions were reported following Elixir Paregorico administration. To our knowledge, this is the first demonstration that Elixir Paregorico administered four times a day for 10 days is safe and does not cause any noticeable toxic effect in healthy volunteers.


Activation of the extracellular calcium-sensing receptor initiates insulin secretion from human islets of Langerhans: involvement of protein kinases.
The extracellular calcium-sensing receptor (CaR) is usually associated with systemic Ca(2+) homeostasis, but the CaR is also expressed in many other tissues, including pancreatic islets of Langerhans. In the present study, we have used human islets and an insulin-secreting cell line (MIN6) to investigate the effects of CaR activation using the calcimimetic R-568, a CaR agonist that activates the CaR at physiological concentrations of extracellular Ca(2+). CaR activation initiated a marked but transient insulin secretory response from both human islets and MIN6 cells at a sub-stimulatory concentration of glucose, and further enhanced glucose-induced insulin secretion. CaR-induced insulin secretion was reduced by inhibitors of phospholipase C or calcium-calmodulin-dependent kinases, but not by a protein kinase C inhibitor. CaR activation was also associated with an activation of p42/44 mitogen-activated protein kinases (MAPK), and CaR-induced insulin secretion was reduced by an inhibitor of p42/44 MAPK activation. We suggest that the beta-cell CaR is activated by divalent cations co-released with insulin, and that this may be an important mechanism of intra-islet communication between beta-cells.


Pharmacokinetics of vancomycin in patients undergoing continuous ambulatory peritoneal dialysis.
The pharmacokinetics of vancomycin were studied in four patients on continuous ambulatory peritoneal dialysis. After a single intravenous infusion of 10 mg/kg of total body weight, multiple blood, urine, and dialysate samples were collected during a 72-h evaluation period. The steady-state volume of distribution was 0.73 +/- 0.07 (mean +/- standard deviation) liters/kg with a beta half-life of 90.2 +/- 24.2 h. The continuous ambulatory peritoneal dialysis clearance of vancomycin was 1.35 +/- 0.35 ml/min, and the serum clearance was 6.4 +/- 1.1 ml/min. Peritoneal dialysate concentrations of vancomycin were rapidly attained after the intravenous infusion and averaged 2.2 +/- 0.7 mg/liter throughout the 72-h observation period. A loading dose of 23 mg/kg followed by a maintenance dose of 17 mg/kg every 7 days should attain and maintain therapeutic serum and dialysate concentrations. More frequent dosing may be necessary for less susceptible organisms.


[Effects of exopolysaccharide from Tolypocladium sinense on murine immunocytes in vitro].
To elucidate the effects of exopolysaccharide from Tolypocladium sinense on murine immunocytes in vitro. Extracted exopolysccharide (EPS) from cultured Tolypocladium sinense. The effects of EPS on mouse immune parameters were detected in vitro using cell culture techniques. The results indicated that EPS might significantly not only promote mouse macrophage neutral red uptake ability and cytotoxicity (P < 0.05), but also stimulate their thymus lymphocytes proliferation (P < 0.05). EPS may elevate murine cellular immunity to a certain.


DH & DHS Data Reform Program (Victoria): Progress to Date.
The Department of Health and Department of Human Services (DH & DHS) Data Reform Program (formerly the DH & DHS Information Management (IM) Strategy) was established to improve the efficiency of data collection and reporting arrangements between the departments and external organisations and individuals. The Data Reform Program is being undertaken incrementally and focuses on reducing the proliferation and duplication of program data collections, improving program data integrity and the timely feedback of collected information to program data providers. To achieve the objectives of the Data Reform Program, the Department of Health has centralised and strengthened governance processes to improve the management and impact of its data collection and reporting requirements of external organisations and individuals. As part of the Data Reform Program, specialist data management tools and resources have also been developed to support data reform within DH and DHS.


Reconstitution of TCR Signaling Using Supported Lipid Bilayers.
Biochemical reconstitution has served as an important tool for understanding the mechanisms of many cellular processes including DNA replication, transcription, translation, vesicle trafficking, and ubiquitin-mediated proteolysis. Here, we demonstrate that biochemical reconstitution can be applied to studying a complex signaling pathway involving as many as 12 proteins or protein complexes acting at the surface of model membranes. We show that a temporal sequence of events in activated T cells beginning with phosphorylation of the T cell receptor and culminating in the activation of actin polymerization can be replicated in vitro. Our reconstitution demonstrates the sufficiency of these proteins in producing many of the complex behaviors observed during T cell activation. The ability to manipulate all of the components, measure reaction rates, and observe molecular behaviors, including at single molecule resolution, has enabled us to gain insight into some of the important biochemical features of this signaling pathway such as microcluster formation. The same system could be adapted to study other membrane-proximal signaling pathways, including growth factor receptors, death receptors, and Eph receptors.


Testing for associations between systolic blood pressure and single-nucleotide polymorphism profiles obtained from sparse principal component analysis.
Hypertension is a prevalent condition linked to major cardiovascular conditions and multiple other comorbidities. Genetic information can offer a deeper understanding about susceptibility and the underlying disease mechanisms. The Genetic Analysis Workshop 18 (GAW18) provides abundant genotype data to determine genetic associations for being hypertensive and for the underlying trait of systolic blood pressure (SBP). The high-dimensional nature of this data promotes dimension reduction techniques to remove excess noise and also synthesize genetic information for complex, polygenic traits. For both measured and simulated phenotype data from GAW18, we use sparse principal component analysis to obtain sparse genetic profiles that represent the underlying data structures. We then detect associations between the obtained sparse principal components (PCs) and SBP, a major indicator of hypertension, following up by investigating the sparse PCs for genetic structure to gain insight into new patterns. After adjusting for multiple testing, 27 of 122 PCs were significantly associated with measured SBP, offering a large number of components to investigate. Considering the top 3 PCs, linked genetic regions have been identified; these may act in unison while associated with SBP. Simulated data offered similar results. Sparse PCs can offer a new data-driven approach to structuring genotype data and understanding the genetic mechanics behind complex, polygenic traits such as hypertension.


Removal of acid-labile protecting groups on carbohydrates using water-tolerant and recoverable vanadyl triflate catalyst.
Acetal, trityl, and TBDMS protecting groups on saccharides were subjected to alcoholysis using a catalytic amount of vanadyl triflate in an MeOH-CH2Cl2 solvent system. The configuration at the anomeric positions of saccharides was retained, and no glycosidic bond cleavage and oxidation of sulfides were observed. The presented method was easily implemented, compatible with diverse functional groups, and regioselective in some cases.


Molecular diversity and ecology of microbial plankton.
The history of microbial evolution in the oceans is probably as old as the history of life itself. In contrast to terrestrial ecosystems, microorganisms are the main form of biomass in the oceans, and form some of the largest populations on the planet. Theory predicts that selection should act more efficiently in large populations. But whether microbial plankton populations harbour organisms that are models of adaptive sophistication remains to be seen. Genome sequence data are piling up, but most of the key microbial plankton clades have no cultivated representatives, and information about their ecological activities is sparse.


A Machine Learning Approach for Hot-Spot Detection at Protein-Protein Interfaces.
Understanding protein-protein interactions is a key challenge in biochemistry. In this work, we describe a more accurate methodology to predict Hot-Spots (HS) in protein-protein interfaces from their native complex structure compared to previous published Machine Learning (ML) techniques. Our model is trained on a large number of complexes and on a significantly larger number of different structural- and evolutionary sequence-based features. In particular, we added interface size, type of interaction between residues at the interface of the complex, number of different types of residues at the interface and the Position-Specific Scoring Matrix (PSSM), for a total of 79 features. We used twenty-seven algorithms from a simple linear-based function to support-vector machine models with different cost functions. The best model was achieved by the use of the conditional inference random forest (c-forest) algorithm with a dataset pre-processed by the normalization of features and with up-sampling of the minor class. The method has an overall accuracy of 0.80, an F1-score of 0.73, a sensitivity of 0.76 and a specificity of 0.82 for the independent test set.


Assessing the Reliability of the Framework for Equitable and Effective Teaching With the Many-Facet Rasch Model.
This manuscript reports results of an empirical assessment of a newly developed measure designed to assess apprentice teaching proficiency. In this study, Many Facets Rasch model software was used to evaluate the psychometric quality of the Framework for Equitable and Effective Teaching (FEET), a rater-mediated assessment. The analysis focused on examining variability in (1) supervisor severity in ratings, (2) level of item difficulty, (3) time of assessment, and (4) teacher apprentice proficiency. Added validity evidence showed moderate correlation with self-reports of apprentice teaching. The findings showed support for the FEET as yielding reliable ratings with a need for added rater training.


p53 gene mutational rate, Gleason score, and BK virus infection in prostate adenocarcinoma: Is there a correlation?
Prostate cancer represents the second leading cause of cancer deaths in Western countries. Viral infections could play a role in prostate carcinogenesis. Human polyomavirus BK (BKV) is a possible candidate because of its transforming properties. In this study, BKV sequences in urine, blood, fresh, and paraffin-embedded prostate cancer samples from 26 patients were searched using Q-PCR analysis. T antigen (TAg) and p53 localization in neoplastic cells were evaluated by immunohistochemical analysis. Also, the presence of mutations in 5-9 exons of p53 gene was analyzed. Results showed that BKV-DNA was found in urine (54%), plasma (31%), and in fresh prostate cancer specimens (85%). The analysis of p53 gene evidenced several mutations in high Gleason patients, according to tumor advanced stage. Immunohistochemical analysis results evidenced the localization of p53 and TAg into cytoplasm, whereas in TAg-negative tumors, p53 was nuclear. This study suggests that BKV acts as cofactor in the pathogenesis of prostate cancer. These observations emphasize previous studies regarding the cellular pathways that may be deregulated by BKV.


Mendelian segregation of normal CAG trinucleotide repeat alleles at three autosomal loci.
Segregation ratio distortion (SRD) with preferential transmission of expanded CAG alleles has been reported in Machado-Joseph disease (MJD/SCA3), spinocerebellar ataxia type I (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA). We have examined the transmission frequencies of alleles in normal heterozygotes at these disease loci in 377 pairs of twins and their parents and find no evidence for SRD.


Evolution and trends of hikikomori: a bibliometrics analysis.
Hikikomori is the Japanese term for the phenomenon of young adults isolating themselves from society and becoming reclusive. This study aims to examine the evolution and distribution of hikikomori, as well as identify the major players and institutions involved in hikikomori research. The searches, which were conducted in Scopus database identified 286 academic research works pertaining to hikikomori research. The findings indicate that hikikomori has attracted the attention of academic researchers in both the East and the West, with a consistent increase in research output since the Internet revolution over the past decade. The study highlights the potential for additional research on hikikomori and provides a benchmark for new researchers entering the field.


Effect of the decompressive extent on the magnitude of the spinal cord shift after expansive open-door laminoplasty.
A retrospective study to analyze the effect of decompressive extent on the posterior shift of spinal cord after expansive open-door laminoplasty (ELAP). To investigate the effect of decompressive extent on cord shift distance after ELAP, and determine the morphologic limitations of posterior approach when the cervical alignment is lordotic or straight. It is still controversial on the effect of space available for spinal cord at the level cephalad to the decompression with cord shift. Moreover, there is less understanding regarding the significance of decompressive extent of laminoplasty in relation to spinal cord shift and clinical outcome. Preoperative and postoperative MRIs of 76 patients with a straight or lordotic cervical spine who had undergone cervical laminoplasty were reviewed and evaluated retrospectively. Radiographic parameters including cervical sagittal alignment, space available at the level cephalad, the thickness of compressive mass, and the average anterior subarachnoid space were measured. Laminoplasty was performed from C1 to C7 in 11 cases (CI group), C2 to C7 in 30 cases (CII group), and C3 to C7 in 35 cases (CIII group). According to whether the anterior indirect decompression was adequate or not, CII and CIII groups were further divided into two subgroups, the noncontact group in which the spinal cord was completely separated from the anterior compressive mass after laminoplasty, and the contact group in which there was residual cord compression after laminoplasty. The recovery rate that based on the Japanese Orthopedic Association score was calculated for each patient. There were statistically significant differences in the average anterior subarachnoid space among CI, CII, and CIII groups (P < 0.05);the average anterior subarachnoid space was the largest in CI group, and the smallest in CIII group. The space available at the level cephalad had strong sigmoidal correlation with cord postoperative shift in CIII group (R = 0.91). A higher neurologic recovery rate (69% ± 20% vs. 29% ± 11%; P < 0.05) in the noncontact group after surgery than in the contact group, with a similar follow-up period. The posterior decompression extent is a main factor affecting cord shift distance after laminoplasty in the context of a straightened or lordotic cervical curvature. The space available at the levels cephalad is a key factor to predict cord shift distance in laminoplasty from C3 to C7. Neurologic recovery rate after ELAP is affected by whether the anterior indirect decompression was adequate or not.


Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.


Foraging patch selection in winter: a balance between predation risk and thermoregulation benefit.
In winter, foraging activity is intended to optimize food search while minimizing both thermoregulation costs and predation risk. Here we quantify the relative importance of thermoregulation and predation in foraging patch selection of woodland birds wintering in a Mediterranean montane forest. Specifically, we account for thermoregulation benefits related to temperature, and predation risk associated with both illumination of the feeding patch and distance to the nearest refuge provided by vegetation. We measured the amount of time that 38 marked individual birds belonging to five small passerine species spent foraging at artificial feeders. Feeders were located in forest patches that vary in distance to protective cover and exposure to sun radiation; temperature and illumination were registered locally by data loggers. Our results support the influence of both thermoregulation benefits and predation costs on feeding patch choice. The influence of distance to refuge (negative relationship) was nearly three times higher than that of temperature (positive relationship) in determining total foraging time spent at a patch. Light intensity had a negligible and no significant effect. This pattern was generalizable among species and individuals within species, and highlights the preponderance of latent predation risk over thermoregulation benefits on foraging decisions of birds wintering in temperate Mediterranean forests.


Adherence to local antimicrobial guidelines for initial treatment of community-acquired infections.
Adherence to antimicrobial guidelines is key to ensuring a correct treatment of severe infections and to lessening misuse of broad-spectrum antimicrobials. We conducted a retrospective cross-sectional study at the Emergency Department of Aalborg University Hospital, North Denmark Region. Our aim was to examine adherence to local antimicrobial guidelines in the empirical treatment of community-acquired infections and to identity any predictors of guideline non-adherence. We identified 1,555 patients who had blood cultures performed and were admitted to the medical emergency department in 2016. We reviewed the medical charts of 755 patients and included those who received at least one antibiotic prescription within the first 24 hours of admission. We excluded patients with known immunodeficiency, severe renal failure or hospitalisation within the previous month. Of the 383 included patients, 203 (53%) received guideline-concordant antibiotic treatment. The treatment was guideline-concordant in 41% of patients with suspected sepsis of unknown origin, in 44% with pneumonia and in 37% with urinary tract infections. Patients with underlying chronic obstructive pulmonary disease (25%) received guideline-concordant treatment significantly more often (83%, p < 0.01) than other groups. Adherence to local antimicrobial guidelines was not high. Further studies are needed to identify barriers to guideline adherence. None. The study was registered with the Danish Data Protection Agency (R. no. 2008-58-0028).


White matter microstructural variability mediates the relation between obesity and cognition in healthy adults.
Obesity has been linked with structural and functional brain changes. However, the impact of obesity on brain and cognition in aging remains debatable, especially for white matter. We therefore aimed to determine the effects of obesity on white matter microstructure and potential implications for cognition in a well-characterized large cohort of healthy adults. In total, 1255 participants (50% females, 19-80 years, BMI 16.8-50.2 kg/m2) with diffusion-weighted magnetic resonance imaging at 3T were analysed. Tract-based spatial statistics (TBSS) probed whether body mass index (BMI) and waist-to-hip ratio (WHR) were related to fractional anisotropy (FA). We conducted partial correlations and mediation analyses to explore whether obesity or regional FA were related to cognitive performance. Analyses were adjusted for demographic, genetic, and obesity-associated confounders. Results showed that higher BMI and higher WHR were associated with lower FA in multiple white matter tracts (p < 0.05, FWE-corrected). Mediation analyses provided evidence for indirect negative effects of higher BMI and higher WHR on executive functions and processing speed through lower FA in fiber tracts connecting (pre)frontal, visual, and associative areas (indirect paths, |ß| ≥ 0.01; 99% |CI| > 0). This large cross-sectional study showed that obesity is correlated with lower FA in multiple white matter tracts in otherwise healthy adults, independent of confounders. Moreover, although effect sizes were small, mediation results indicated that visceral obesity was linked to poorer executive functions and lower processing speed through lower FA in callosal and associative fiber tracts. Longitudinal studies are needed to support this hypothesis.


Absolute configuration of natural diastereoisomers of 6beta-hydroxyhyoscyamine by vibrational circular dichroism.
The absolute configuration of the two natural diastereoisomers of 6beta-hydroxyhyoscyamine has been determined using vibrational circular dichroism (VCD) spectroscopy. The predicted VCD and IR spectra of (3R,6R,2'S)-6beta-hydroxyhyoscyamine (1) and (3S,6S,2'S)-6beta-hydroxyhyoscyamine (2) were calculated using density functional theory (DFT) with the B3LYP functional and 6-31G(d) basis set and considering the eight lower energy conformations of each diastereoisomer. In both cases, the first four conformers showed the N-Me group in the syn orientation, permitting the formation of a hydrogen bond between the hydroxy group at the tropane ring and the tertiary nitrogen atom. In addition the eight conformers showed an intramolecular hydrogen bond between the hydroxy and carbonyl groups of the tropic ester moiety. The calculated IR spectra of both molecules showed good agreement with the experimental spectra, while comparison of the experimental and calculated VCD spectra showed that the absolute configuration of dextrorotatory 6beta-hydroxyhyoscyamine is (3R,6R,2'S), while the levorotatory isomer is (3S,6S,2'S).


Resistance to cassava mosaic disease in transgenic cassava expressing antisense RNAs targeting virus replication genes.
African cassava mosaic virus (ACMV) is a major contributor to cassava mosaic disease (CMD), the economically most important and devastating disease of cassava in Africa. We have developed transgenic cassava plants with increased ACMV resistance using improved antisense RNA technology by targeting the viral mRNAs of Rep (AC1), TrAP (AC2) and REn (AC3). Viral DNA replication assays in detached leaves demonstrated that replication of two ACMV isolates was strongly reduced or inhibited in most transgenic lines. After ACMV infection of plants using biolistic inoculation, several lines remained symptomless at lower infection pressure (100 ng viral DNA/plant). Symptom development was reduced and attenuated even at higher DNA doses. Transgenic ACMV-resistant plants had significantly reduced viral DNA accumulation in their infected leaves. Short sense and antisense RNAs specific to AC1 were identified in transgenic lines expressing AC1 antisense RNA, suggesting that the short RNAs mediate interference by post-transcriptional gene silencing. Our results demonstrate that resistance to ACMV infection of cassava can be achieved with high efficacy by expressing antisense RNAs against viral mRNAs encoding essential non-structural proteins, providing a new tool to combat CMD in Africa.


Antireduction: an ancient strategy fit for future.
While antioxidants are on everyone's lips, antireductants are their much less-known counterparts. Following an antioxidant's definition, an antireductant prevents the chemical reduction of another compound by undergoing reduction itself. Antireductants have been traced back as far as the origin of life, which they facilitated by removal of atmospheric dihydrogen, H2 Moreover, as electron acceptors, antireductants equipped the first metabolic pathways, enabling lithoautotrophic microbial growth. When the Earth's atmosphere became more oxidizing, certain antireductants revealed their Janus-face by acting as antioxidants. Both capacities, united in one compound, were detected in primary as well as plant secondary metabolites. Substantiated by product identification, such antireductants comprise antiradicals (e.g. carotenoids) up to diminishers of ruminal methane emission (e.g. fumarate, catechin or resveratrol). Beyond these Janus-faced, multifunctional compounds, the spectrum of antireductants extends to pure electron-attractors (e.g. atmospheric triplet oxygen, O2, for plant root and gut protection). Current and prospective fields of antireductant application range from health promotion over industrial production to environmental sustainability.


1-beta-D-arabinofuranosylcytosine inhibits borna disease virus replication and spread.
Borna disease virus (BDV) is a nonsegmented, negative-strand RNA virus that causes neurological diseases in a variety of warm-blooded animal species. There is general consensus that BDV can also infect humans, being a possible zoonosis. Although the clinical consequences of human BDV infection are still controversial, experimental BDV infection is a well-described model for human neuropsychiatric diseases. To date, there is no effective treatment against BDV. In this paper, we demonstrate that the nucleoside analog 1-beta-D-arabinofuranosylcytosine (Ara-C), a known inhibitor of DNA polymerases, inhibits BDV replication. Ara-C treatment inhibited BDV RNA and protein synthesis and prevented BDV cell-to-cell spread in vitro. Replication of other negative-strand RNA viruses such as influenza virus or measles virus was not inhibited by Ara-C, underscoring the particularity of the replication machinery of BDV. Strikingly, Ara-C treatment induced nuclear retention of viral ribonucleoparticles. These findings could not be attributed to known effects of Ara-C on the host cell, suggesting that Ara-C directly inhibits the BDV polymerase. Finally, we show that Ara-C inhibits BDV replication in vivo in the brain of infected rats, preventing persistent infection of the central nervous system as well as the development of clinical disease. These findings open the way to the development of effective antiviral therapy against BDV.


Communication after laryngectomy. An assessment of patient satisfaction.
To determine the satisfaction of patients with their current method of alaryngeal communication. To focus primarily on the patients' perception of their own speech. A retrospective review of patients who underwent total laryngectomy for malignancy identified 4 groups of patients. A survey using a mailed questionnaire was used to compare groups. Tertiary care university hospital, University of Texas Medical Branch at Galveston. Forty-seven patients underwent total laryngectomy for cancer and survived. Thirty-one of the 47 patients responded to the survey. Patients were divided into 4 groups by their current method of communication: (1) tablet writers; (2) esophageal speech; (3) electrolarynx; and (4) tracheoesophageal speech. Satisfaction with communication, satisfaction with speech quality, ability to communicate over telephone, limitation of interaction with others, and satisfaction with quality of life. Patients in group 4 were significantly more satisfied with their speech (P < .001), perceived their speech to be of better quality (P < .001), had improved ability to communicate over the telephone (P < .001), and had less limitation of their interactions with others (P < .004). Patients in group 4 also rated their overall quality of life higher (P = .23). Although many studies in the past have demonstrated the objective superiority of tracheoesophageal speech compared with other methods of alaryngeal communication, most studies have focused on the intelligibility of speech judged by listeners. This study demonstrates that patients who use tracheoesophageal speech rate their own speech significantly higher than patients who use other methods and most likely have an overall superior quality of life.


The role of calcitonin gene-related peptide and substance P in the pathogenesis of dialysis headache.
The present study aims to establish the role of serum CGRP and SP levels in the disease pathophysiology in patients with dialysis headache not accompanied by primary or secondary headaches, and also whether there is a correlation between these vasoactive peptides and the severity of headache. This study was designed as prospective and multicenter. A total of 30 dialysis headache patients and 30 patients without headache as the control group in the Nephrology outpatient clinics which implement similar dialysis procedures were included in the study. Blood samples were taken from all the patients before hemodialysis, and post-hemodialysis samples were collected. CGRP and SP contents in serum samples were measured using the ELISA method with detection kits. A total of 60 patients were included in the study with 17 female and 13 male patients in the dialysis headache group and 18 female and 12 male patients in the control group, and there were no significant differences in sex and age between the groups. CGRP levels in the headache group were found to be significantly higher compared with the control group both before and after hemodialysis. Furthermore, pre-hemodialysis CGRP levels were significantly higher than post-hemodialysis CGRP levels in both the headache and control groups. Serum SP levels in the headache group were found to be higher compared with the control group both before and after hemodialysis, there was no significant difference between the groups. Even though SP levels in both groups decreased after hemodialysis, there was again no significant difference between the groups. No correlation was found between the patients' severity of headache and serum CGRP and SP levels. This study concludes that CGRP and SP, even though the latter is not statistically significant, play a role in the pathophysiology of the dialysis headache, and further studies with a larger and more specific patient population may reveal the relationship between the neuropeptides and dialysis headache more clearly.


Clinical trials with the new antitussive levodropropizine in adult bronchitic patients.
The results of 6 clinical trials involving a total of 174 patients are reported. Levodropropizine (S(-)-3-(4-phenyl-piperazin-1-yl)-propane-1,2-diol, DF 526) was compared in double-blind manner with placebo, morclofone and cloperastine. The antitussive activity and therapeutic efficacy of the drug were shown to be greater than those of placebo and morclofone and similar to those of cloperastine. Levodropropizine was effective in about 80% of patients; in responders, cough frequency was reduced by an average of 33-51%. Levodropropizine was generally well tolerated and mild side-effects were reported for only 3% of patients.


Planned Versus Unplanned Risks: Evidence for Subtypes of Risk Behavior in Adolescence.
Risk behavior escalates during adolescence, contributing to substantial morbidity and mortality. This study examined whether individual differences in personality and neurocognitive function previously shown to be associated with overall frequency of risk behavior are differentially related to two proposed subtypes of adolescent risk behavior: planned and unplanned. Adolescents (N = 69, 49% male, M = 15.1 years, SD = 1.0), completed a battery of self-report measures and neurocognitive tasks. Several personality and neurocognitive variables predicted membership in the planned versus unplanned risk group: perceiving the benefits of risk behaviors to outweigh risks, more accurately identifying beneficial choices in a modified Iowa Gambling Task (IGT), and performing more advantageously on the IGT and the Game of Dice Task. This study supports the hypothesis that planned versus unplanned risk behavior comprise distinct subtypes in adolescence. Understanding the mechanisms underlying these subtypes may inform prevention programs targeting specific contributors to adolescent risk behavior.


Simultaneous determination of Cd, Cu, Mn, Ni, Pb and Zn in nail samples by inductively coupled plasma mass spectrometry (ICP-MS) after tetramethylammonium hydroxide solubilization at room temperature: comparison with ETAAS.
A simple method is described for the determination of Cd, Cu, Mn, Ni, Pb and Zn in nails by using inductively coupled plasma mass spectrometry (ICP-MS) or electrothermal atomic absorption spectrometry (ETAAS). Prior to analysis, 10-20 mg of nail samples were accurately weighed into (15 mL) conical tubes. Then, 1 mL of 25% (w/v) tetramethylammonium hydroxide (TMAH) solution was added to the samples, incubated at room temperature overnight and then further diluted to 10 mL with 1% (v/v) HNO(3). After that, samples were directly analyzed. Rhodium was used as internal standard for ICP-MS analysis. Method detection limits (3 s, n=20) were 0.1, 3.0, 1.0, 4.5, 1.5, 5.0 ng g(-1) for Cd, Cu, Mn, Ni, Pb and Zn, respectively for ICP-MS, and 24, 26, 30, 143, 130 and 1000 ng g(-1), respectively for ETAAS. The key issue addressed here is the elimination of the acid digestion prior to analysis. Moreover, with the use of the proposed method there is a considerable improvement in the sample throughput comparing to the traditional methods using microwave-assisted acid sample digestion prior to analysis. For validation purposes, six ordinary nail samples were solubilized and then directly analyzed by ICP-MS and ETAAS, with no statistical difference between the two techniques at 95% level on applying the t-test.


[Oxidative metabolism of HIV-infected macrophages: the role of glutathione and a pharmacologic approach].
Oxidative stress and glutathione deficiency seem to play a major role in the pathogenesis of HIV infection, as suggested by the increased survival of HIV-infected patients treated with N-acetylcysteine, a prodrug of glutathione. However, beneficial effects of GSH-replenishing drugs are restricted in vivo by the high concentrations needed to obtain biological effects and their low bioavailability. In this study, we evaluated the antiretroviral and antioxidant activities of new more lipophilic GSH-replenishing molecules, in macrophages infected in vitro with HIV-1. In these experimental conditions, a prodrug of N-acetylcystéine and beta-mercaptoethylamine, I-152 demonstrated a potent anti-HIV activity, increased intracellular GSH level, and decreased TNF-alpha production. Altogether, these results suggest that I-152 could be beneficial as adjuvant therapy of antiretrovirals in HIV-infected patients, especially in those with damages to the central nervous system or with mitochondrial damages associated with highly active antiretroviral therapy.


[Vasculitis in children].
Vasculitis is a group of rare diseases of unknown etiology, characterised by inflammation and necrosis of blood vessels, contributing to various clinical consequences. The variety of clinical symptoms and presence of symptoms from various syndromes often make the diagnosis difficult. Until now no causal treatment has been established. In order to achieve a remission of the disease, corticosteroids and immunosuppressive therapy are recommended.


Biodiversity of leaf litter fungi in streams along a latitudinal gradient.
Global patterns of biodiversity have emerged for soil microorganisms, plants and animals, and the extraordinary significance of microbial functions in ecosystems is also well established. Virtually unknown, however, are large-scale patterns of microbial diversity in freshwaters, although these aquatic ecosystems are hotspots of biodiversity and biogeochemical processes. Here we report on the first large-scale study of biodiversity of leaf-litter fungi in streams along a latitudinal gradient unravelled by Illumina sequencing. The study is based on fungal communities colonizing standardized plant litter in 19 globally distributed stream locations between 69°N and 44°S. Fungal richness suggests a hump-shaped distribution along the latitudinal gradient. Strikingly, community composition of fungi was more clearly related to thermal preferences than to biogeography. Our results suggest that identifying differences in key environmental drivers, such as temperature, among taxa and ecosystem types is critical to unravel the global patterns of aquatic fungal diversity.


High-efficiency grating coupler based on fast directional optimization and robust layout strategy in 130 nm CMOS process.
We experimentally demonstrated a high-efficiency grating coupler by combining an interleaved etch and apodized structure for fiber-to-chip coupling. The grating coupler was optimized using the fast directional optimization method to achieve apodization. The grating coupler utilized a layout strategy involving an extended mask to avoid alignment errors for a multi-etch structure. The coupling efficiency was measured to be -2.2 dB at a wavelength of 1549 nm with a 3 dB bandwidth of 47 nm. The grating coupler, having no gold reflector, subwavelength index matching structure, or additional material layers, was fabricated using a commercial silicon photonics process with a minimum feature size of 140 nm. This grating coupler design provides a robust and effective coupling scheme and the proposed method can be employed to adopt the design in accordance with standard foundry design rules.


In Vivo Evaluation of White Matter Abnormalities in Children with Duchenne Muscular Dystrophy Using DTI.
Duchenne muscular dystrophy is an X-linked disorder characterized by progressive muscle weakness and prominent nonmotor manifestations, such as a low intelligence quotient and neuropsychiatric disturbance. We investigated WM integrity in patients with Duchenne muscular dystrophy using DTI. Fractional anisotropy and mean, axial, and radial diffusivity (DTI measures) were used to assess WM microstructural integrity along with neuropsychological evaluation in patients with Duchenne muscular dystrophy (n = 60) and controls (n = 40). Exon deletions in the DMD gene were confirmed using multiplex ligation-dependent probe amplification. Patients were classified into proximal (DMD Dp140+) and distal (DMD Dp140-) subgroups based on the location of the exon deletion and expression of short dystrophin Dp140 isoform. WM integrity was examined using whole-brain Tract-Based Spatial Statistics and atlas-based analysis of DTI data. The Pearson correlation was performed to investigate the possible relationship between neuropsychological scores and DTI metrics. The mean ages of Duchenne muscular dystrophy and control participants were 8.0 ± 1.2 years and 8.2 ± 1.4 years, respectively. The mean age at disease onset was 4.1 ± 1.8 years, and mean illness duration was 40.8 ± 25.2 months. Significant differences in neuropsychological scores were observed between the proximal and distal gene-deletion subgroups, with more severe impairment in the distal-deletion subgroup (P < .05). Localized fractional anisotropy changes were seen in the corpus callosum, parietal WM, and fornices in the patient subgroup with Dp140+, while widespread changes were noted in the Dp140- subgroup. The Dp140+ subgroup showed increased axial diffusivity in multiple WM regions relative to the Dp140- subgroup. No significant correlation was observed between clinical and neuropsychological scores and diffusion metrics. Widespread WM differences are evident in patients with Duchenne muscular dystrophy relative to healthy controls. Distal mutations in particular are associated with extensive WM abnormalities and poor neuropsychological profiles.


Effects of alterations in left ventricular filling, contractility, and systemic vascular resistance on the ascending aortic blood velocity waveform of normal subjects.
To confirm the consistent effects on Doppler-measured aortic blood flow velocity waveform variables of alterations in left ventricular preload, afterload, and inotropy using pharmacologic and physiologic maneuvers. Medical school laboratory. Healthy volunteers. Increasing infusion rates of dobutamine (1.25 to 5 micrograms/kg.min), esmolol (1.25 to 5 mg/min), phentolamine (1.25 to 5 mg/min), methoxamine (1.25 to 5 mg/min), metaraminol (1.25 to 5 mg/min), and placebo (1.25 to 5 mL of 0.9% saline/min) and increasing plasma removal (0.5 to 1 L) in awake, rested, supine subjects. Ascending aortic blood flow was measured by the suprasternal Doppler approach allowing calculation of waveform variables of stroke distance and minute distance (linear measures of stroke volume and cardiac output), peak velocity, mean acceleration and flow time corrected for heart rate. An index of systemic vascular resistance was obtained by dividing mean systemic BP by the minute distance. Inotropic changes predominantly affected peak velocity and mean acceleration. Changes in preload mainly affected the flow time corrected for heart rate, whereas afterload changes had an intermediate effect. Unsuspected but subsequently confirmed hemodynamic effects were seen with esmolol and metaraminol. Aortic blood flow velocity waveform variables measured by Doppler ultrasound can be used to noninvasively follow changes in left ventricular preload, afterload, and inotropy.


The ultimate gift. Interview by Elizabeth Lynch.
Donating an organ to someone you do not know is a huge decision. But for one nurse, it was something she felt she had to do.


Downregulation of miRNA-29, -23 and -21 in urine of Duchenne muscular dystrophy patients.
To study the signature of 87 urinary miRNAs in Duchenne muscular dystrophy (DMD) patients, select the most dysregulated and determine statistically significant differences in their expression between controls, ambulant (A) and nonambulant (NA) DMD patients, and patients on different corticosteroid regimens. Patients/materials & methods: Urine was collected from control (n = 20), A (n = 31) and NA (n = 23) DMD patients. miRNA expression was measured by reverse transcription-quantitative PCR. miR-29c-3p was significantly downregulated in A DMD patients while miR-23b-3p and miR-21-5p were significantly downregulated in NA DMD patients compared with age-matched controls. miR-29c-3p, miR-23b-3p and miR-21-5p are promising novel noninvasive biomarkers for DMD, and miR-29c-3p levels are differentially affected by different steroid regimens, supporting the antifibrotic effect of steroid therapy.


Use of a novel beta-tricalcium phosphate-based bone void filler as a graft extender in spinal fusion surgeries.
Synthetic bone void fillers are gaining acceptance as graft extenders in spinal surgery. One such product is an ultraporous formulation of nanometer-sized particles of beta-tricalcium phosphate (beta-TCP). An ongoing prospective open-label, randomized, observer-blinded, comparative study evaluated the efficacy and safety of a novel beta-TCP bone void filler as an additive to autogenous bone graft material in patients undergoing spinal fusion. Posterolateral instrumented or noninstrumented spinal fusion was performed at a single level or multiple levels with or without additional interbody fusion. Patients received autogenous bone on 1 side and autogenous bone augmented with extender (in a 1:1 ratio based on the weight of the materials) on the opposite side, each patient serving as his or her own control. The graft material was placed at the level of the facet joints and the intertransverse processes. Patients were randomized to receive the extender on either the right or the left side. This article is a preliminary report on patients who have undergone this procedure.


Effects of repetition rate, phase, and frequency on the auditory brainstem response in neonates and adults.
This study evaluated the effects of stimulus repetition rate, phase, and frequency on the auditory brainstem response (ABR) in normal-hearing neonates and adults. In both neonates and adults, the results clearly showed large ABR wave V latency differences between condensation and rarefaction for low-frequency stimuli. Phase dependent latency effects are believed to be a result of the phase-sensitive low-frequency neurons. Increasing stimulus repetition rate produced greater wave V latency shift in neonates than in adults. The consequences of rate changes were independent of stimulus phase and frequency.


GC-MS determination of levoglucosan in atmospheric particulate matter collected over different filter materials.
An analytical procedure consisting of ultrasonic extraction with acetonitrile, trimethylsilylation and GC-MS analysis was applied to the determination of levoglucosan (LG) in aerosol collected with three different filter types (teflon, quartz, glass). Methyl-beta-L-arabinopyranoside (MA) and sedoheptulosan (SD, 2,7-anhydro-beta-D-altro-heptulopyranose) were investigated as recovery standards. Mean recovery of MA decreased in the order 82%, 78%, 74% and that of SD from 82% to 76% and 32% from teflon, quartz and glass blank filters, respectively, whereas recovery of LG was little affected (80-86%). The extraction efficiency from glass filters could be increased by using methanol in place of acetonitrile, but recovery of SD remained inadequate. Internal calibration with MA was linear in the 0.035-70 microg mL(-1) LG concentration interval. The method was tested on different air filter materials utilized to sample PM(10) in outdoor air and wood smoke emitted from stove and boiler encompassing LG concentrations from 0.06 to 230 microg m(-3) with RSD in the 2.9-22% range. The application of the method in aerosol sampled in alpine zones of Italy revealed a linear correlation between LG and PM(10) concentrations with a higher proportion of LG in winter and in rural areas where the use of woody biomass for residential heating is widespread.


Neuroimaging characteristics of ruptured aneurysm as predictors of outcome after aneurysmal subarachnoid hemorrhage: pooled analyses of the SAHIT cohort.
OBJECT Neuroimaging characteristics of ruptured aneurysms are important to guide treatment selection, and they have been studied for their value as outcome predictors following aneurysmal subarachnoid hemorrhage (SAH). Despite multiple studies, the prognostic value of aneurysm diameter, location, and extravasated SAH clot on computed tomography scan remains debatable. The authors aimed to more precisely ascertain the relation of these factors to outcome. METHODS The data sets of studies included in the Subarachnoid Hemorrhage International Trialists (SAHIT) repository were analyzed including data on ruptured aneurysm location and diameter (7 studies, n = 9125) and on subarachnoid clot graded on the Fisher scale (8 studies; n = 9452) for the relation to outcome on the Glasgow Outcome Scale (GOS) at 3 months. Prognostic strength was quantified by fitting proportional odds logistic regression models. Univariable odds ratios (ORs) were pooled across studies using random effects models. Multivariable analyses were adjusted for fixed effect of study, age, neurological status on admission, other neuroimaging factors, and treatment modality. The neuroimaging predictors were assessed for their added incremental predictive value measured as partial R(2). RESULTS Spline plots indicated outcomes were worse at extremes of aneurysm size, i.e., less than 4 or greater than 9 mm. In between, aneurysm size had no effect on outcome (OR 1.03, 95% CI 0.98-1.09 for 9 mm vs 4 mm, i.e., 75th vs 25th percentile), except in those who were treated conservatively (OR 1.17, 95% CI 1.02-1.35). Compared with anterior cerebral artery aneurysms, posterior circulation aneurysms tended to result in slightly poorer outcome in patients who underwent endovascular coil embolization (OR 1.13, 95% CI 0.82-1.57) or surgical clipping (OR 1.32, 95% CI 1.10-1.57); the relation was statistically significant only in the latter. Fisher CT subarachnoid clot burden was related to outcome in a gradient manner. Each of the studied predictors accounted for less than 1% of the explained variance in outcome. CONCLUSIONS This study, which is based on the largest cohort of patients so far analyzed, has more precisely determined the prognostic value of the studied neuroimaging factors. Treatment choice has strong influence on the prognostic effect of aneurysm size and location. These findings should guide the development of reliable prognostic models and inform the design and analysis of future prospective studies, including clinical trials.


Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote.
In prokaryotes, few studies have applied the flippase (FLP)/P1-flippase recombination target (LoxP-FRT) recombination system to switch gene expression. This study developed a new method for switching gene expression by constructing an FLP/LoxP-FRT site-specific recombination system in Escherichia coli. To this end, we placed the Nos terminator flanked by a pair of LoxP-FRT in front of enhanced green fluorescent protein (eGFP). The Nos terminator was used to block the expression of the eGFP. When a plasmid expressing FLP was available, deletion of the Nos terminator would allow expression of eGFP. The regulatory effect was demonstrated by eGFP expression. The efficiency of the gene switch was calculated as high as 89.67%. The results showed that the FLP/LoxP-FRT recombinase system could be used as a gene switch to regulate gene expression in prokaryotes. This new method for switching gene expression could simplify the gene function analysis in E. coli and other prokaryotes, as well as eukaryotes.


Pediatric Trigger Digits.
Pediatric trigger thumb (PTT) and finger (PTF) are upper extremity deformities that frequently go unrecognized by providers. Early recognition by pediatricians and caregivers is vital because PTT is successfully treated nonoperatively in more than 95% of patients if diagnosed early. Similarly, PTF can be successfully treated nonoperatively in 67% of patients. Although PTT is typically benign and 10 times more common, PTF may be associated with underlying concurrent medical conditions, such as juvenile rheumatoid arthritis, diabetes, mucopolysaccharide and lysosomal disorders, and trisomy 18. Routine examinations consisting of full hand range of motion should be performed in all children. Clinicians should be aware of the importance of conservative treatment options for PTT and PTF and the value of screening for underlying medical conditions associated with PTF.


[Jejunal intussusceptions as a lead point ectopic pancreatic tissue in a 1-year-old male. Case report].
intussusception is the most common cause of acute bowel obstruction in infants and young children. Incidence has been reported as 1.5 to 4 cases per 1,000 live births. Most intussusceptions are ileocecocolic; jejunal intussusceptions in children is extremely rare. a 1-year-old male was admitted to the emergency department with diarrheal evacuations, without mucus or blood, crying and irritable. Previously he had melaena in one occasion. The abdomen was found soft and depressible and low pain. He was treated with ceftriaxone, omeprazole and metoclopramide. Two days after admission he had melaena and rectal bleeding. Plain abdominal radiography showed air fluid levels. Abdominal surgery was performed finding jejunal intussusceptions which were reduced. Demonstrable lesion as a lead point was a small tumor that was removed. The pathologist's report showed pancreatic islets cells. jejunal intussusceptions in children are extremely rare and occur at any age. Main symptoms are intermittent abdominal pain and vomiting. Ultrasonography is the study of choice. Often a lesion is demonstrable as a lead point for the intussusceptions and therefore requires open or laparoscopic surgery. In this case, it was unusual to have the presence of ectopic pancreatic tissue as a lead point.


First-principles study of controllable contact types in Janus MoSH/GaN van der Waals heterostructure.
The search for contact materials with low contact resistance and tunable Schottky barrier (SB) height of two-dimensional (2D) materials is important for improving the electronic performance. Inspired by the recently synthesized metallic Janus MoSH, this study employs first-principles calculations to investigate the electronic structure, mechanical properties, and interface characteristics of Janus MoSH/GaN and MoHS/GaN van der Waals (vdW) heterostructures. We find that both heterostructures exhibit isotropic mechanical properties and form p-type Schottky barrier contacts (p-ShC) and the SB height of MoHS/GaN is smaller than that of the MoSH/GaN heterostructure. The variation in SB height and contact type under biaxial strain and electric field is also studied for both vdW heterostructures, respectively. Compared to the MoSH/GaN heterostructure, the MoHS/GaN heterostructure can transition to Ohmic contact (OhC) under biaxial strain and electric field, making the S-face contact of MoSH with GaN a more effective contact approach. These findings could provide a new pathway for the design of controllable Schottky nanodevices and high-performance electronic devices on GaN-based vdW heterostructures.


SARS-CoV-2 RNA detection in the air and on surfaces in the COVID-19 ward of a hospital in Milan, Italy.
The COVID-19 outbreak has rapidly progressed worldwide finding the health system, scientists and society unprepared to face a little-known, fast spreading, and extremely deadly virus. Italy is one of the countries hardest hit by the pandemic, resulting in healthcare facilities bearing heavy burdens and severe restrictive measures. Despite efforts to clarify the virus transmission, especially in indoor scenarios, several aspects of SARS-CoV-2 spread are still rudimentary. This study evaluated the contamination of the air and surfaces by SARS-CoV-2 RNA in the COVID-19 isolation ward of a hospital in Milan, Italy. A total of 42 air and surface samples were collected inside five different zones of the ward including contaminated (COVID-19 patients' area), semi-contaminated (undressing room), and clean areas. SARS-CoV-2 RNA detection was performed using real time reverse transcription polymerase chain reaction. Overall, 24.3% of swab samples were positive, but none of these were collected in the clean area. Thus, the positivity rate was higher in contaminated (35.0%) and semi-contaminated (50.0%) areas than in clean areas (0.0%; P<0.05). The most contaminated surfaces were hand sanitizer dispensers (100.0%), medical equipment (50.0%), medical equipment touch screens (50.0%), shelves for medical equipment (40.0%), bedrails (33.3%), and door handles (25.0%). All the air samples collected from the contaminated area, namely the intensive care unit and corridor, were positive while viral RNA was not detected in either semi-contaminated or clean areas. These results showed that environmental contamination did not involve clean areas, but the results also support the need for strict disinfection, hand hygiene and protective measures for healthcare workers as well as the need for airborne isolation precautions.


The Effects of Biomaterial Implant Wear Debris on Osteoblasts.
Aseptic loosening subsequent to periprosthetic osteolysis is the leading cause for the revision of arthroplasty failure. The biological response of macrophages to wear debris has been well established, however, the equilibrium of bone remodeling is not only dictated by osteoclastic bone resorption but also by osteoblast-mediated bone formation. Increasing evidence shows that wear debris significantly impair osteoblastic physiology and subsequent bone formation. In the present review, we update the current state of knowledge regarding the effect of biomaterial implant wear debris on osteoblasts. The interaction of osteoblasts with osteoclasts and macrophages under wear debris challenge, and potential treatment options targeting osteoblasts are also presented.


Extracorporeal Membrane Oxygenation Support for Cardiac Dysfunction Due to Kawasaki Disease Shock Syndrome.
Background: Kawasaki disease (KD) is usually characterized as an inflammatory vasculitis during early childhood, which predominantly involves medium-sized arteries and is treated with intravenous γ-globulin (IVIG) and oral aspirin. KD with hemodynamic instability, characterized by systolic blood pressure decreasing by more than 20% below the normal range, is defined as Kawasaki disease shock syndrome (KDSS). The pathogenesis of KDSS is still not comprehensively understood. Life-threatening cardiogenic shock can occur during the acute phase of KDSS, while the mechanism of cardiac dysfunction due to KDSS is still controversial, and such cases are rarely reported. Here, we present the application of veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) for cardiac function support of a child with KDSS. By doing so, it will be a reminder that KDSS can cause severe cardiac dysfunction, and we should stay vigilant at the early stage of the disease to distinguish KDSS from toxic septic shock in the first place and initiate the appropriate treatment at the right moment, in order to prevent such patients from having irreversible outcomes.


DNA methylation variations are required for epithelial-to-mesenchymal transition induced by cancer-associated fibroblasts in prostate cancer cells.
Widespread genome hypo-methylation and promoter hyper-methylation of epithelium-specific genes are hallmarks of stable epithelial-to-mesenchymal transition (EMT), which in prostate cancer (PCa) correlates with castration resistance, cancer stem cells generation, chemoresistance and worst prognosis. Exploiting our consolidated 'ex-vivo' system, we show that cancer-associated fibroblasts (CAFs) released factors have pivotal roles in inducing genome methylation changes required for EMT and stemness in EMT-prone PCa cells. By global DNA methylation analysis and RNA-Seq, we provide compelling evidence that conditioned media from CAFs explanted from two unrelated patients with advanced PCa, stimulates concurrent DNA hypo- and hyper-methylation required for EMT and stemness in PC3 and DU145, but not in LN-CaP and its derivative C4-2B, PCa cells. CpG island (CGI) hyper-methylation associates with repression of genes required for epithelial maintenance and invasion antagonism, whereas activation of EMT markers and stemness genes correlate with CGI hypo-methylation. Remarkably, methylation variations and EMT-regulated transcripts almost completely reverse qualitatively and quantitatively during MET. Unsupervised clustering analysis of the PRAD TCGA data set with the differentially expressed (DE) and methylated EMT signature, identified a gene cluster of DE genes defined by a CAF+ and AR- phenotype and worst diagnosis. This gene cluster includes the relevant factors for EMT and stemness, which display DNA methylation variations in regulatory regions inversely correlated to their expression changes, thus strongly sustaining the ex-vivo data. DNMT3A-dependent methylation is essential for silencing epithelial maintenance and EMT counteracting genes, such as CDH1 and GRHL2, that is, the direct repressor of ZEB1, the key transcriptional factor for EMT and stemness. Accordingly, DNMT3A knock-down prevents EMT entry. These results shed light on the mechanisms of establishment and maintenance of coexisting DNA hypo- and hyper-methylation patterns during cancer progression, the generation of EMT and cell stemness in advanced PCa, and may pave the way to new therapeutic implications.


Functional characterization of the T4 DNA ligase: a new insight into the mechanism of action.
ATP-dependent DNA ligases are essential enzymes in both DNA replication and DNA repair processes. Here we report a functional characterization of the T4 DNA ligase. One N-terminal and two C-terminal deletion mutants were expressed in Escherichia coli as histidine- tagged proteins. An additional mutant bore a substitution of Lys159 in the active site that abolished ATP binding. All the proteins were tested in biochemical assays for ATP-dependent self-adenylation, DNA binding, nick joining, blunt-end ligation and AMP- dependent DNA relaxation. From this analysis we conclude that binding to DNA is mediated by sequences at both protein ends and plays a key role in the reaction. The enzyme establishes two different complexes with DNA: (i) a transient complex (T.complex) involving the adenylated enzyme; (ii) a stable complex (S.complex) requiring the deadenylated T4 DNA ligase. The formation of an S. complex seems to be relevant during both blunt-end ligation and DNA relaxation. Moreover the inactive His-K159L substitution mutant, although unable to self-adenylate, still possesses AMP-dependent DNA nicking activity.


[Diagnosis and treatment of osteoporosis and rheumatoid arthritis in accordance with German guidelines. Results of a survey of patients, primary care physicians and rheumatologists].
In a cross-sectional study the prevalence of osteoporosis and osteopenia in patients with rheumatoid arthritis (ORA study) was investigated. Additionally, patients, their family doctors and rheumatologists were surveyed on their awareness of osteoporosis in RA, prevention, diagnosis, treatment and use of guidelines.In the years 2005 and 2006 a total of 532 patients with RA (98 men, 434 women) aged 23-87 years were consecutively recruited from 9 German centers for rheumatology. Clinical examination included a detailed documentation of osteoporosis medication. Dual-energy X-ray absorptiometry (DXA) was used to measure bone mineral density (BMD) at the lumbar spine and neck of the femur. Questionnaires on osteoporosis were sent to 119 family doctors (87 men, 32 women) and 44 rheumatologists (30 men, 14 women).The survey showed that rheumatologists had a higher awareness of osteoporosis in RA and compared to family doctors they estimated a higher frequency and tested RA patients more often for osteoporosis. In line with osteoporosis guidelines rheumatologists and family doctors saw an indication for densitometry in RA patients on steroid therapy and/or low intensity trauma fractures. In contrast to the 2006 recommendations of osteoporosis guidelines 50% of family doctors and rheumatologists preferred bisphosphonate off-label-therapy for premeopausal women with RA and comorbid glucocorticoid-induced osteoporosis. On the other hand 50% of premenopausal RA patients with osteoporosis did not receive any osteoporosis medication.The survey revealed a high degree of guideline compliance in diagnosing osteoporosis in RA but deficits were observed in the administration of osteoporosis medication, especially in premenopausal women.


Livestock odours and quality of life of neighbouring residents.
Neighbours of intensive livestock production facilities frequently complain of odour annoyance. They are also concerned about potential negative health effects of environmental exposures to livestock emissions. Quality of life (QoL) was assessed in residents of a rural community neighbouring an area with high concentration of animal farms. A postal cross-sectional survey was carried out among the 4,537 residents, aged 18-44 years. Of these, 3,112 (69 %) responded to questions on annoyance by livestock odours (4-point scale), on QoL (assessed by the short form 12, SF-12), and on potential confounders (age, gender, respiratory symptoms, smoking, living on or close to a farm, and employment status). SF-12 scores were available for 2745 (88 %) subjects. Sixty-one percent of the respondents complained about unpleasant odours, 91 % of these accused livestock as source of these odours. Physical and emotional SF-12 scores were inversely related to annoyance scores. Better risk communication might improve QoL in concerned neighbours of intensive livestock production facilities.


Cardiac-disease-induced PTSD (CDI-PTSD): A systematic review.
The goal of the current systematic review was to provide an overview of the findings in the field of Cardiac-Disease-Induced Posttraumatic Stress Disorder (CDI-PTSD) in order to establish CDI-PTSD as a valid diagnostic entity for a wide spectrum of cardiac diseases and related medical procedures. In accordance with PRISMA guidelines, we conducted a systematic electronic literature search. Of the 3202 citations identified, 150 studies meeting the selection criteria were reviewed. Our main findings were that the prevalence of CDI-PTSD ranged between 0% and 38% (averaging at 12%) and was highly dependent on the assessment tool used. The most consistent risk factors are of a psychological nature (e.g., pre-morbid distress). The consequences of CDI-PTSD range from psychosocial difficulties to lack of adherence and heightened mortality rates. Much inconsistency in the field was found with regard to patients who present with diagnoses other than acute coronary syndrome (e.g., cardiac arrest) and who undergo potentially traumatic medical procedures (e.g., defibrillator implantation). Yet the current review seems to strengthen the conceptualization of CDI-PTSD as a valid diagnostic entity, at least with regard to acute cardiac events.


Pausing of RNA polymerase during in vitro transcription of the tryptophan operon leader region.
RNA polymerase molecules pause at a single site during in vitro transcription of the tryptophan (trp) operon leader region. Pausing was observed when DNA templates derived from Escherichia coli. Salmonella typhimurium, and Klebsiella aerogenes were used. Fingerprint analyses showed that the major RNA species produced by the transcriptional pause is 91 nucleotides long. A minor RNA species 90 nucleotides long was also detected. Single-round transcription experiments were used to study the kinetics of pausing. Time course, pulse-chase, and delayed-labeling experiments suggest that every RNA polymerase molecule transcribing the trp leader region pauses. A suboptimal ribonucleoside triphosphate concentrations, the half-life of paused-leader RNA was approximately 3 min at 22 degrees C and 0.7 min at 37 degrees C. At near-optimal ribonucleoside triphosphate concentrations, the half-time of the paused species dropped to about 0.3 min at 22 degrees C. The appearance and half-life of the paused species were unaffected by salt concentration, rho factor, guanosine 3'-5'-bis(diphosphate), or point mutations in the trp attenuator region. It is postulated that transcriptional pausing may play a role in maintaining the synchronization of transcription and translation that is vital in the control of transcription termination at the trp operon attenuator.


Dosimetric characteristics of electron beams produced by a mobile accelerator for IORT.
Energy and angular distributions of electron beams with different energies were simulated by Monte Carlo calculations. These beams were generated by the NOVAC7 system (Hitesys, Italy), a mobile electron accelerator specifically dedicated to intra-operative radiation therapy (IORT). The electron beam simulations were verified by comparing the measured dose distributions with the corresponding calculated distributions. As expected, a considerable difference was observed in the energy and angular distributions between the IORT beams studied in the present work and the electron beams produced by conventional accelerators for non-IORT applications. It was also found that significant differences exist between the IORT beams used in this work and other IORT beams with different collimation systems. For example, the contribution from the scattered electrons to the total dose was found to be up to 15% higher in the NOVAC7 beams. The water-to-air stopping power ratios of the IORT beams used in this work were calculated on the basis of the beam energy distributions obtained by the Monte Carlo simulations. These calculated stopping power ratios, s(w,air), were compared with the corresponding s(w,air) values recommended by the TRS-381 and TRS-398 IAEA dosimetry protocols in order to estimate the deviations between a dosimetry based on generic parameters and a dosimetry based on parameters specifically obtained for the actual IORT beams. The deviations in the s(w,air) values were found to be as large as up to about 1%. Therefore, we recommend that a preliminary analysis should always be made when dealing with IORT beams in order to assess to what extent the possible differences in the s(w,air) values have to be accounted for or may be neglected on the basis of the specific accuracy needed in clinical dosimetry.


Design, Synthesis, and Acute Toxicity Assays for Novel Thymoquinone Derivative TQFL12 in Mice and the Mechanism of Resistance to Toxicity.
TQFL12 is a novel derivative designed and synthesized on the basis of Thymoquinone (TQ) which is extracted from Nigella sativa seeds. We have demonstrated that TQFL12 was more effective in the treatment of TNBC than TQ. In order to directly reflect the acute toxicity of TQFL12 in vivo, in this study, we designed, synthesized, and compared it with TQ. The mice were administered drugs with different concentration gradients intraperitoneally, and death was observed within one week. The 24 h median lethal dose (LD50) of TQ was calculated to be 33.758 mg/kg, while that of TQFL12 on the 7th day was 81.405 mg/kg, and the toxicity was significantly lower than that of TQ. The liver and kidney tissues of the dead mice were observed by H&E staining. The kidneys of the TQ group had more severe renal damage, while the degree of the changes in the TQFL12 group was obviously less than that in the TQ group. Western blotting results showed that the expressions of phosphorylated levels of adenylate-activated protein kinase AMPKα were significantly up-regulated in the kidneys of the TQFL12 group. Therefore, it can be concluded that the acute toxicity of TQFL12 in vivo is significantly lower than that of TQ, and its anti-toxicity mechanism may be carried out through the AMPK signaling pathway, which has a good prospect for drug development.


Permanganate oxidation of diclofenac: The pH-dependent reaction kinetics and a ring-opening mechanism.
In this work, the fate of diclofenac (DCF) during permanganate (Mn(VII)) oxidation was investigated at environmentally relevant pH conditions (from 5 to 9). The batch experiments showed that the kinetics of the Mn(VII)/DCF reaction follows a second-order rate law with an apparent rate constant of 1.57±0.02 M(-1) s(-1) at pH 7 and 20 °C. The half-value of DCF was calculated to be 37.5 min, when the concentration of Mn(VII) (0.4 mM) was 20-fold excess of DCF. The pH-dependence of the reaction kinetics was investigated, and the DCF reactivity with Mn(VII) was found to decrease with increasing pH. The second-order rate constants were then quantitatively described by incorporating the species distribution of DCF. A lower reactivity of the anionic DCF (DCF(-)) in comparison with its neutral counterpart (DCF(0)) was most likely attributable to the interaction between the ionized carboxylate group and amine nitrogen position, which can reduce the nucleophilicity of amine nitrogen by inductive and resonance effects. Moreover, a range of degradation products and the corresponding structures were proposed on the basis of the LC-Q-TOF-MS analysis. A detailed ring-opening reaction mechanism was proposed as follows: Mn(VII) acts as an electrophile to attack the amine moiety, leading to the formation of the primary intermediate products 2,6-dichloroaniline and 5-hydroxy-diclofenac, which can be further transformed. The further degradation proceeded through a multistep process including ring-opening, decarboxylation, hydroxylation, and cyclation reactions.


Effects of different drugs on the curative effect, stress responses, and the circulatory system of patients with hypertensive trigeminal neuralgia.
This research aimed to analyze the effects of stellate nerve block with different drugs on the curative effect, stress responses, and the circulatory system of patients with hypertensive trigeminal neuralgia (TN). A retrospective analysis of 82 patients with hypertensive TN admitted to our hospital from January 2019 to January 2021 was conducted, and the patients were divided into a control group and an observation group according to different drugs. The pain visual analogue scale (VAS) scores were determined between the 2 groups before treatment and at 1, 2, 3, 7, and 30 d after treatment. The mean arterial pressure (MAP) and heart rate (HR) were measured in the 2 groups of patients before treatment and immediately after treatment (T0), half an hour after treatment (T1), 1 h after treatment (T2), and 6 h after treatment (T3). The left ventricular wall thickness (LVWT), left ventricular end systolic volume (LVESV), left ventricular ejection fraction (LVEF), and fraction shortening (FS) were detected in the 2 groups before treatment and at T0-T2. Patient satisfaction was also scored, and the incidence of adverse reactions was assessed. The VAS scores of the 2 groups of patients decreased significantly after treatment at 1, 2, 3, 7, and 30 d. The MAP and HR indicators of the 2 groups decreased gradually at T0-T2, and gradually recovered to levels before treatment at the T3 time point. The MAP and HR indicators of the observation group were significantly lower than those of the control group at T0-T2. After treatment, the levels of LVWT, LVESV, LVEF, and FS in the observation group at the T0-T2 time points were significantly lower than those of the control group. Additionally, after treatment, the satisfaction of the observation group was significantly higher than that of the control group. The total incidence of adverse reactions in the observation group was significantly lower than that in the control group. For patients with hypertensive TN, a single ropivacaine stellate nerve block can significantly relieve pain, and has little effect on heart function.


A haemolytic plaque forming assay for identifying cells producing anti-DNA antibodies.
A murine hybridoma cell line (aDNA35I9) secreting anti-DNA antibodies was used as a model for haemolytic plaque forming cells in an assay where DNA-conjugated sheep red blood cells (DNA-SRBC) were used as target cells. DEAE-dextran, employed to abolish the anti-complementary activity of agar gel, completely inhibited anti-DNA plaques. This problem was solved by using agarose instead of agar. Since the occurrence of small plaques may make reading of the test difficult, it was established that plaque size could be increased by decreasing the antigen density on the target cells. Free DNA in the gel inhibited plaque formation, indicating the specificity of the assay. Spleen cells from mice of the strains MRL/MP and NZB/W which are known to develop a stage of autoimmunity, produced plaques in numbers which were correlated to the age of the mice and to the anti-DNA antibody level in serum.


Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties.
To date, the primary treatments for Alzheimer's disease with proven efficacy have been acetylcholinesterase inhibitors that prevent the hydrolysis of acetylcholine (ACh) in the synaptic cleft, thereby prolonging its activity. Although these agents have some benefit in alleviating cognitive impairment, they have limited clinical utility because of insufficient efficacy and marginal tolerability. Within the last decade, there has been much experimental support for the use of therapeutics that directly target nicotinic ACh receptors (nAChRs) to improve cognitive function and slow neurodegenerative disease progression. These findings have spurred considerable research efforts to develop ligands selective for nAChRs, such as ABT-418 (Arneric et al., 1995), SIB-1553 (Bontempi et al., 2001), TC-2403 (Lippiello et al., 1996), and TC-2559 (Bencherif et al., 2000). There is abundant evidence that nAChR modulators have the potential to alleviate cognitive impairment in demented states. In addition to improving cognitive function, a large body of research implicates a role for nAChRs in neuroprotection, suggesting potential for disease modification. An impact of nAChR agonists on disease progression would provide an advantage over currently available treatments for memory loss. The profile of previous nAChR-targeted clinical candidates has not been adequate to warrant further development owing to poor oral bioavailability, side effects, and/or lack of efficacy. Thus, a challenge in nAChR drug design and development has been the reduction of undesirable effects that result from activity at specific nAChRs in the CNS and PNS, including cardiovascular toxicity, emesis, seizures, and hypothermia.


Radioiodine (I-131) therapy and the incidence of hypothyroidism.
Radioiodine (I-131) is one of the accepted forms of treatment for thyrotoxicosis. The major drawback of this treatment is the definite incidence of hypothyroidism, which is either early or late, and is cumulative. We set out to analyse the local incidence of this outcome. Patients with hyperthyroidism, treated with radioiodine from 1984 to end of 1989, and still on follow-up with the Department of Nuclear Medicine, Singapore General Hospital were analysed for the incidence of hypothyroidism. Three hundred and eighty-two patients were analysed (305 females, 77 males). Their ages ranged from 14 to 85 years (mean 48.2, SD 11.1 years). The doses of radioiodine ranged from 4 to 18 mCi (mean 7.6 mCi, SD 1.8 mCi). Two hundred and sixty-two patients who received I-131 only required a single dose, while 87 needed one repeated dose of I-131, and 33 needed more than 2 doses. Of the 382 patients, 271(70.9%) became clinically hypothyroid, 6 (1.6%) were subclinically hypothyroid, 100 (26.7%) were euthyroid and 3 (0.8%) remained hyperthyroid. One hundred and eighty-one patients (47.4%) were clinically hypothyroid at the end of 1 year, and an average rise of 4.8% per year was observed from the second to the fifth year. From the sixth year onwards, the average incidence of hypothyroidism was 1% per year. I-131 is indeed an effective means of controlling thyrotoxicosis (99.2% were no longer hyperthyroid). The main problem with this treatment is hypothyroidism, and this is easily managed with L-thyroxine.


A mathematical model of communication between groups of circadian neurons in Drosophila melanogaster.
In the fruit fly, circadian behavior is controlled by a small number of specialized neurons, whose molecular clocks are relatively well known. However, much less is known about how these neurons communicate among themselves. In particular, only 1 circadian neuropeptide, pigment-dispersing factor (PDF), has been identified, and most aspects of its interaction with the molecular clock remain to be elucidated. Furthermore, it is speculated that many other peptides should contribute to circadian communication. We have developed a relatively detailed model of the 2 main groups of circadian pacemaker neurons (sLNvs and LNds) to investigate these issues. We have proposed many possible mechanisms for the interaction between the synchronization factors and the molecular clock, and we have compared the outputs with the experimental results reported in the literature both for the wild-type and PDF-null mutant. We have studied how different the properties of each neuron should be to account for the observations reported for the sLNvs in the mutant. We have found that only a few mechanisms, mostly related to the slowing down of nuclear entry of a circadian protein, can synchronize neurons that present these differences. Detailed immunofluorescent recordings have suggested that, whereas in the mutant, LNd neurons are synchronized, in the wild-type, a subset of the LNds oscillate faster than the rest. With our model, we find that a more likely explanation for the same observations is that this subset is being driven outside its synchronization range and displays therefore a complex pattern of oscillation.


Use of health services by black children according to payment mechanism.
The use patterns of approximately 2,600 black children, categorized according to type of insurance (Medicaid, private health insurance or no insurance), were analyzed. All children were enrolled in an urban pediatric primary care program that attempted to increase access to health care by poor children. Medicaid recipients used health-care services more than their counterparts who had private or no insurance. All groups received significant levels of preventive care. The percentage of health care received in the emergency room did not vary significantly among the groups. These results suggest that special delivery systems can be effective in reaching poor children and eliminating usage differentials according to income.


Morphologic Change of In Vivo Porcine Liver Under 13 mm Hg Pneumoperitoneum Pressure.
Clinically, the total and residual liver volume must be accurately calculated before major hepatectomy. However, liver volume might be influenced by pneumoperitoneum during surgery. Changes in liver volume change also affect the accuracy of simulation and augmented reality navigation systems, which are commonly first validated in animal models. In this study, the morphologic changes in porcine livers in vivo under 13 mm Hg pneumoperitoneum pressure were investigated. Twenty male pigs were scanned with contrast-enhanced computed tomography without pneumoperitoneum and with 13 mm Hg pneumoperitoneum pressure. The surface area and volume of the liver and the vascular diameter of the aortic lumen, inferior vena cava lumen, and portal vein lumen were measured. There were statistically significant differences in the surface area and volume of the liver (P=0.000), transverse diameter of the portal vein (P=0.038), longitudinal diameter of the inferior vena cava (P=0.033), longitudinal diameter of the portal vein (P=0.036), vascular cross-sectional area of the inferior vena cava (P=0.028), and portal vein (P=0.038) before and after 13 mm Hg pneumoperitoneum pressure. This study indicated that the creation of pneumoperitoneum at 13 mm Hg pressure in a porcine causes liver morphologic alterations affecting the area and volume, as well as the diameter of a blood vessel.