Transport, metabolism, and in vivo population pharmacokinetics of the chloro benztropine analogs, a class of compounds extensively evaluated in animal models of drug abuse.
Recently, extensive behavioral research has been conducted on the benztropine (BZT) analogs with the goal of developing successful therapeutics for cocaine abuse. The present study was conducted to characterize the contribution of dispositional factors in mediating the behavioral differences among the chloro BZT analogs and to identify cytochrome P450 enzymes involved in their metabolism. Bidirectional transport and efflux studies of four of the chloro BZT analogs were conducted. Screening with a panel of human and rat Supersomes was performed for 4',4''-diCl BZT. In addition, pharmacokinetic and brain distribution studies for 4'-Cl and 4',4''-diCl BZT in Sprague-Dawley rats were conducted. The permeability of the chloro analogs ranged from 8.26 to 32.23 and from 1.37 to 21.65 x 10(-6) cm/s, whereas the efflux ratios ranged from 2.1 to 6.9 and from 3.3 to 28.4 across Madin-Darby canine kidney-multidrug resistance 1 (MDCK-MDR1) and Caco-2 monolayers, respectively. The P-glycoprotein (P-gp) inhibitor verapamil reduced the efflux ratios and enhanced the absorptive transport of the chloro BZT analogs. 4',4''-diCl BZT was a substrate of human CYP2D6 and 2C19 and rat 2C11 and 3A1. The brain uptake for 4'-Cl and 4',4''-diCl BZT was comparable and higher than previously reported for cocaine (brain-to-plasma partition coefficient = 4.6-4.7 versus 2.1 for cocaine). The rank order for t(1/2) was 4',4''-diCl BZT >> 4'-Cl BZT > cocaine and for steady-state volume of distribution was 4'-Cl BZT > 4',4''-diCl BZT >> cocaine. In conclusion, the chloro analogs differ significantly in their clearance and duration of action, which correlates to their behavioral profiles and abuse liability. Furthermore, these results suggest that the distinctive behavioral profile of these analogs is not due to limited brain exposure.


Clinical efficacy and safety of tolterodine compared to placebo in detrusor overactivity.
We evaluated the efficacy, patient acceptability and side effect profile of tolterodine, a new antimuscarinic agent for treating bladder overactivity. In our randomized, placebo controlled, parallel group study 123, 129 and 64 patients 18 years old or older with proved detrusor overactivity (idiopathic detrusor instability or detrusor hyperreflexia) were randomized to receive 1 or 2 mg. tolterodine, or placebo, respectively, twice daily for 12 weeks. Main outcome measures were number of voids per 24 hours, urine volume per void and episodes of urge incontinence per 24 hours on a frequency-volume chart with detailed recording of side effects. After 12 weeks of treatment mean number of voids per 24 hours plus or minus standard deviation decreased from 11.2 +/- 3.1 to 9.0 +/- 2.6 with the 2 mg. dosage (p = 0.0045 versus placebo). At this dose mean urine volume per void increased from 155 +/- 52 to 190 +/- 70 ml. (p <0.0001 versus placebo), while mean number of incontinence episodes per 24 hours decreased from 3.6 +/- 4.0 to 1.8 +/- 3.1 (p = 0.19 versus placebo). Similar efficacy was observed in patients receiving the 1 mg. dose. Severe dry mouth was reported by only 2, 1 and 2% of patients given the 1 and 2 mg. dose, and placebo, respectively. There was no clinical or electrocardiographic evidence of significant cardiac adverse events. Tolterodine administration resulted in a significant decrease in the frequency of voiding and improved voided volume but it was seldom associated with troublesome or severe side effects.


Shape effect on the electronic state and nonlinear optical properties in the regulable Y-shaped quantum dots under applied electric field.
The electronic state and nonlinear optical properties in the Y-shaped quantum dots has been theoretically investigated by adjusting the shape with the applied electric field. Within the effective-mass approximation, the energy levels and the wave functions of the system are obtained by means of the finite difference method. The results show that both the strength or the in-plane orientation of external electric field and the shape of regulable Y-shaped quantum dots have a significant influence on the electronic state, optical absorption coefficients and the refractive index changes.


How have outcomes for patients with follicular lymphoma changed with the addition of monoclonal antibodies?
The outcome for patients with follicular lymphoma (FL) has substantially improved over the last few years. This improved survival appears to be largely related to the increasingly widespread use of anti-CD20 monoclonal antibody (mAb) rituximab in the therapy of FL today, either in combination with chemotherapy, for remission 'induction' and more recently as 'maintenance' therapy. Encouraging results have also been reported from radiolabelled anti-CD20 mAb or radioimmunotherapy (RIT), which exploits the unique method of action of this approach and high radiosensitivity of FL. High response rates and durable remissions have been seen with both (90)Y Ibritumomab tiuxetan and (131)I Tositumomab, and more recently compelling data are emerging demonstrating the efficacy of using these drugs as consolidation after initial treatment with chemotherapy or rituximab plus chemotherapy combinations. This review will focus on the current approaches and explore the data that has led to the emergence of a new nomenclature appearing in the language of clinicians involved in the treatment of FL, namely 'induction' therapy, 'consolidation' of initial response and 'maintenance' therapy. The current treatment approaches that have led to such increased optimism regarding the therapeutic outcome in FL are evaluated and discussed.


Initial career choices of medical school honors graduates in the early 1970s and 1980s.
To investigate the changes over time in the attractiveness of a number of medical specialties as careers, the author analyzed the initial career pathways of students who graduated with honors in 1972, 1973, 1982, and 1983 from nine of the most prestigious American medical schools. The data were analyzed to discern career selection differences among the total population studied, between the men and women, and between the graduates of public and private institutions. Internal medicine showed statistically significant declines in its attractiveness to the students in all the categories but remained overrepresented as a career choice by honors students compared with its attractiveness to medical students in general for the years studied. Radiology was chosen by an increasing percentage of the honors students in the 1980s, but mostly by students from private medical schools. The men who were honors graduates in the 1980s chose surgery fields more often, while women honors graduates tended to enter pediatrics and obstetrics-gynecology. These data indicate that the career choices of honors graduates in the early 1980s more closely mirrored the career choices of all students entering medical specialty fields and do not reveal gross imbalances. Of the primary care disciplines, only internal medicine attracted fewer honors graduates in the 1980s.


The Use of Station Time Allotments by Fourth Year Medical Students in a Standardized Patient-Based Clinical Skills Examination.
We performed this study to assess medical student use of station time allotments in a standardized patient-based clinical skills assessment. Videotapes of student-SP encounters were reviewed. Total encounter time, and time spend in the physical examination, were recorded in seconds. The mean time use for each station was calculated. Cases were categorized by patient age, case content and acuity. Times were compared across cases. On average, students spent most time in encounters requiring complex interviewing strategies or physical examination maneuvers. Students also spent more time on cases that involved content familiar to them from multiple clerkship disciplines. Many factors are believed to influence the use of station time allotments in SP-based clinical skills assessment. Our findings have provided information helpful for case refinement, and may assist others when planning multi-station examinations.


Tolerance for ambiguity could influence awareness of breast cancer genetic testing and inform health education.
This exploratory study assessed relationships among education, tolerance for ambiguity, and genetic testing awareness in light of implications for cancer genetics education. Cross-sectional analyses were conducted from self-administered written survey data of a breast cancer risk communication trial, including 899 Women's Health patients recruited from 2003 to 2005. The modifying effect of tolerance for ambiguity on the relationship between educational background and breast cancer genetic testing awareness was assessed through logistic regression. There was a statistically significant main effect of education (p < 0.05), but not tolerance for ambiguity, on genetic testing awareness. However, the relationship between education and awareness was stronger among those with high tolerance for ambiguity (p for interaction <0.05), even when controlling for age, race, and breast cancer family history. Among persons with high (>1 SD above the mean) and medium tolerance for ambiguity, the relationship between education and awareness was positive and significant (p = 0.048 and 0.002, respectively). Among participants with low tolerance for ambiguity, the association was not significant. Educational background may predict awareness knowledge of breast cancer genetic testing only for those with higher tolerance for ambiguity. These findings could inform future intervention research concerning education about cancer genetic testing.


Applicability of UV-Curable Binders in High Solid Suspensions for Direct-Ink-Write 3D Printing in Extremely Cold Temperatures.
Leveraging material extrusion 3D printing of high solid suspensions for rapid manufacturing in future space missions requires materials compatible with the unique environments found on the Lunar surface. However, there is currently a lack of selection criteria for materials processable in the harsh environmental conditions on the Moon without significantly altering the 3D printers. Here, we provide valuable insights into the behavior of high solid suspensions at low temperatures to guide informed decision-making for manufacturing in subzero environments. We investigate the effects of direct-ink-write (DIW) printing at -30 °C on the structure-property relationships of UV-curable high solid inks of glass microspheres. We analyze the inks based on extrudability and curability at subzero temperatures to verify extrusion, shape retention, and sufficient solidification, culminating in successful printing at -30 °C. Preferential polymerization among monomers is observed at -30 °C and results in a lower cross-linking density in the final print, with a reduced tensile modulus. However, lower ratios of highly mobile monomers result in the retention of mechanical properties, demonstrating the selection criteria for binder design. Through this work, we highlight the importance of binder formulations used for 3D printing in uncommon environmental conditions that are emerging as tomorrow's manufacturing challenge.


Air Quality Implications of Using Ammonia as a Renewable Fuel: How Low Can NOx Emissions Go?
In addition to their lifecycle carbon emissions, another important issue with decarbonized energy pathways is their air quality, water, or land use implications. This paper considers the air quality issue for ammonia combustion. When directly combusting ammonia, reactions of its N atom with atmospheric oxygen lead to NOx emissions that are O(103) ppm, 2 orders of magnitude higher than EPA limits or the amount emitted by current natural-gas-fired technologies. In order to provide guidance to policymakers and technologists on what is fundamentally possible, this Perspective analyzes the fundamental minimum NOx emissions that can be produced from ammonia combustion. The analysis shows that it is possible to achieve quite low NOx emission levels of O(10) ppm, but these designs differ markedly from those used in today's lean, premixed combustion systems.


Low serum HDL-cholesterol levels are associated with long symptom duration in patients with major depressive disorder.
The purpose of the present study was to examine whether the association between depression and the serum high-density lipoprotein cholesterol (HDL-C) is modified by symptom duration. Depressed patients (n = 88) and an age- and sex-matched group of healthy general population controls (n = 88) underwent a Structured Clinical Interview for DSM-IV (SCID), and depressed participants reported the duration of their symptoms. The serum levels of total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and non-HDL, and the ratios of LDL-C/HDL and TC/HDL-C were assessed. Major depressive disorder (MDD) subjects with a long symptom duration (>or=3 years) had lower levels of HDL-C compared with healthy controls or MDD subjects with a symptom duration <3 years. The likelihood for long symptom duration doubled for each 0.5-mmol/L decrease in HDL-C levels in regression models adjusted for age, gender, marital status, overweight, symptom severity, alcohol consumption, smoking, physical exercise, medication use, and non-HDL-C (P < 0.05). These findings suggest that a low serum HDL-C level, a risk factor for coronary heart disease, is specifically associated with long-term depressive symptomatology.


Morphometric Variation in Pine Wood Nematodes, Bursaphelenchus xylophilus and B. mucronatus, Isolated from Multiple Locations in South Korea.
Intraspecific variation in morphometry of pine wood nematodes Bursaphelenchus xylophilus and B. mucronatus in relation to geographical locations in South Korea was investigated using morphometric characters (body length, a, b and c ratio, stylet length, and spicule length for a male nematode and V (%) value for a female nematode). B. xylophilus was isolated from Pinus thunbergii in Jinju (1998), Ulsan (2000), Yangsan (2000), Mokpo (2001) and Jeju (2004), and from P. densiflora in Gumi (2001). B. mucronatus was isolated from P. thunbergii in Jinju (1991) and from P. densiflora in Milyang (2001). The body length of male and female B. xylophilus had the highest coefficient of variability and showed significant differences among geographical locations. The V (%) value for female B. xylophilus showed the lowest coefficient of variability, changing little with geographical area and host plant. All morphometric characters in B. mucronatus except for stylet length and female body length showed no significant differences between locations or hosts, suggesting they may not be affected by geographical area or host plant.


Binary System for MicroRNA-Targeted Imaging in Single Cells and Photothermal Cancer Therapy.
Abnormal expression of microRNAs (miRNAs) is often associated with tumorigenesis, metastasis, and progression. Among them, miRNA-21 is found to be overexpressed in most of the cancer cells. Here, a binary system is designed for miRNA-21 targeted imaging and photothermal treatment in single cells. The binary system is composed by a pair of probes (probe-1 and probe-2), which are encapsulated in liposomes for cell delivery. Both of the two probes adopt gold nanoparticles (AuNPs) as the core material, and the AuNPs are functionalized with Cy5-marked molecular beacon (MB-1/MB-2 for probe-1/probe-2, respectively). The loop part of MBs are designed to be complementary with miRNA-21. Therefore, after the binary system enters into the cytoplasm, MBs can be opened upon miRNA-21 triggered hybridization, which turns "on" the fluorescence of Cy5 for the localization of miRNA-21. At the same time, a cross-linking between the probes occurs since the far ends of MB-1 and MB-2 are designed to be complementary with each other. The miRNA-induced aggregation shifts the absorption of AuNPs to near-infrared, which can be observed under dark-field microscopy (DFM) and used for the following photothermal therapy. Under near-infrared (NIR) irradiation, MCF-7 breast cancer cells are successfully killed. The proposed system can be further applied in tumor-bearing mice and shows significant therapeutic effect. This work provides a new tool for intracellular miRNA analysis and targeted treatment against cancer.


Subthalamic and striatal neurons concurrently process motor, limbic, and associative information in rats performing an operant task.
Although the subthalamic nucleus (STN) is commonly assumed to be a relay for striatal (STR) output, anatomical evidence suggests the two structures are connected in parallel, raising the possibility that parallel STN and STR firing patterns mediate behavioral processes. The STR is known to play a role in associative and limbic processes, and although behavioral studies suggest that the STN may do so as well, evaluation of this hypothesis is complicated by a lack of pertinent STN physiological data. We recorded concurrent STN and STR firing patterns in rats learning an operant nose-poke task. Both structures responded in similar proportions to task events including instructive cues, discriminative nose-pokes, and sucrose reinforcement. Neuronal responses to reinforcement comprised phasic excitations preceding reinforcement and inhibitions afterward; the inhibition was attenuated when reinforcement was absent. Reinforcement responses occurred more frequently during later training sessions in which discriminative action was required, suggesting that responses were context-dependent. Nose-pokes were typically preceded by excitations; there also was a nonsignificant trend toward inhibition encoding correct nose-pokes. Sustained changes in firing rate coinciding with specific task events suggested that both nuclei were encoding behavioral sequences; this is the first report of such behavior in the STN. Our findings also reveal complex STN responses to reinforcement. Thus both STN and STR neurons show concurrent involvement in motor, limbic, and associative processes.


[Genetic analysis and gene mapping for a salt tolerant mutant at seedling stage in rice].
A salt tolerant mutant at seedling stage was obtained from an M2 population of radiation mutagenesis of an indica rice cultivar R401. The mutant seedlings could survive under the treatment of sodium chloride solution at the concentration of 150 mmol/L, while the wild-type control seedlings withered and died. An F2 population was developed from a cross between a japonica cultivar Nipponbare and the salt tolerant mutant. By investigating the performance of the F2 population under the stress of 150 mmol/L NaCl solution, we found that the mutant phenotype was caused by the recessive mutation of a single gene, temporarily designated SST(t). Bulked segregant analysis (BSA) based on the F2 mapping population revealed that SST(t) is located on chromosome 6. By analyzing 137 typical salt-tolerant F2 plants using molecular markers, SST(t) was mapped in a 2.3 cM (or 406 kb) interval between InDel markers ID26847 and ID27253, with genetic distances of 1.2 cM and 1.1 cM to the two markers, respectively.


Childhood acute lymphoblastic leukemia (ALL) presenting with severe osteolysis: a model to study leukemia-bone interactions and potential targeted therapeutics.
Interference with the molecular mechanisms that generate tumor supportive niches in the bone microenvironment is a rational approach to inhibit the growth of hematological malignancies. However, the advancement of knowledge in this area has been slowed down by the lack of in vitro models to facilitate the screening of potential candidate agents. The rare cases of acute lymphoblastic leukemia (ALL) in children presenting with extensive bone involvement may represent an exaggerated form of some aspects of the normal tumor-bone interactions. Thus, these cases can provide insight into processes that are otherwise challenging to uncover. The authors describe the case of a 6-year-old child who presented with severe osteopenia that resolved at the time of leukemic remission. Compared to control sera, serum taken at disease presentation contained increased levels of a group of osteolytic cytokines and was effective in activating preosteoclast cells in culture. Based on these findings, the authors describe an experimental model to identify agents that would interfere with leukemia mediated osteolytic process.


In vitro antidiabetic and antihypercholesterolemic activities of camel milk protein hydrolysates derived upon simulated gastrointestinal digestion of milk from different camel breeds.
Milk protein hydrolysates derived from 4 camel breeds (Pakistani, Saheli, Hozami, and Omani) were evaluated for in vitro inhibition of antidiabetic enzymatic markers (dipeptidyl peptidase IV and α-amylase) and antihypercholesterolemic enzymatic markers (pancreatic lipase and cholesterol esterase). Milk samples were subjected to in vitro simulated gastric (SGD) and gastrointestinal digestion (SGID) conditions. In comparison with intact milk proteins, the SGD-derived milk protein hydrolysates showed enhanced inhibition of α-amylase, dipeptidyl peptidase IV, pancreatic lipase, and cholesterol esterase as reflected by lower half-maximal inhibitory concentration values. Overall, milk protein hydrolysates derived from the milk of Hozami and Omani camel breeds displayed higher inhibition of different enzymatic markers compared with milk protein hydrolysates from Pakistani and Saheli breeds. In vitro SGD and SGID processes significantly increased the bioactive properties of milk from all camel breeds. Milk protein hydrolysates from different camel breeds showed significant variations for inhibition of antidiabetic and antihypercholesterolemic enzymatic markers, suggesting the importance of breed selection for production of bioactive peptides. However, further studies on identifying the peptides generated upon SGD and SGID of milk from different camel breeds are needed.


Dehydroepiandrosterone induces a neuroendocrine phenotype in nerve growth factor-stimulated chromaffin pheochromocytoma PC12 cells.
The adrenal androgen dehydroepiandrosterone (DHEA) is produced in the inner zone of the adrenal cortex, which is in direct contact to adrenal medullary cells. Due to their close anatomical proximity and tightly intermingled cell borders, a direct interaction of adrenal cortex and medulla has been postulated. In humans congenital adrenal hyperplasia due to 21-hydroxylase deficiency results in androgen excess accompanied by severe adrenomedullary dysplasia and chromaffin cell dysfunction. Therefore, to define the mechanisms of DHEA action on chromaffin cell function, we investigated its effect on cell survival and differentiation processes on a molecular level in the chromaffin cell line PC12. DHEA lessened the positive effect of NGF on cell survival and neuronal differentiation. Nerve growth factor (NGF)-mediated induction of a neuronal phenotype was inhibited by DHEA as indicated by reduced neurite outgrowth and decreased expression of neuronal marker proteins such as synaptosome-associated protein of 25 kDa and vesicle-associated membrane protein-2. We examined whether DHEA may stimulate the cells toward a neuroendocrine phenotype. DHEA significantly elevated catecholamine release from unstimulated PC12 cells in the presence but not absence of NGF. Accordingly, DHEA enhanced the expression of the neuroendocrine marker protein chromogranin A. Next, we explored the possible molecular mechanisms of DHEA and NGF interaction. We demonstrate that NGF-induced ERK1/2 phosphorylation was reduced by DHEA. In summary, our data show that DHEA influences cell survival and differentiation processes in PC12 cells, possibly by interacting with the ERK1/2 MAPK pathway. DHEA drives NGF-stimulated cells toward a neuroendocrine phenotype, suggesting that the interaction of intraadrenal steroids and growth factors is required for the maintenance of an intact adrenal medulla.


[The neurochemical mechanisms regulating the burst activity in isolated endogenous oscillators in the snail: the role of monoamines and opioid peptides].
Electrical activity of three different isolated identified bursting neurons in the Helix brain is studied. A new method for isolation of identified neurons is worked out. The data obtained demonstrate that all three neurons are endogenous oscillators: isolated neurons reveal spontaneous changes from inactive condition to regular activity, from regular activity to bursting one and on the contrary. Moreover it is shown that bursting activity in all three isolated neurons can be regulated by the same neurochemical agents: serotonin, enkephalins; combined action of dopamine and enkephalins stimulates bursting activity in these neurons, while dopamine inhibits it. The possible role of these neurochemical mechanisms in generation of rhythm for different rhythmical functions is discussed.


Factors associated with fertility intention among women with systemic lupus erythematosus in China: A cross-sectional study.
This study aims to explore the status and influencing factors of fertility intention in women of childbearing age with systemic lupus erythematosus (SLE). A total of 158 SLE patients admitted to the Affiliated Hospital of Nantong University from February 2021 to February 2022 were selected for a cross-sectional study. The dependent variable in this study was the fertility intention of lupus women of childbearing age, so the questionnaire was selected: "In view of your disease, do you plan to have children? Yes/no" as the measurement statement. Lupus patients were divided into fertility intention groups and non-fertility intention groups. The questionnaire survey comprises following scales: Hospital Anxiety and Depression Scale (HADS), Multidimensional Fatigue Inventory (MFI-20), Female Sexual Distress Scale-Revised (FSDS-R), and others. Independent t-test, one-way ANOVA, Mann-Whitney U test, and binary logistic regression were used for analysis. The results showed that 20.9% of lupus patients in this study had a fertility intention. The fertility intention was associated with age, reproductive history, reproductive concerns, sexual distress, fatigue, family function, social support, depression, and sleep. Binary logistic regression showed that physical fatigue (OR 3.56, 95% CI 1.048-12.07) and personal health (OR 2.50, 95% CI 1.065-5.853) had significant predictors of fertility intention. Our study identified a lower fertility intention in SLE patients who had reproductive concerns, sexual distress, family dysfunction, and fatigue. We encourage healthcare institutions to provide counseling services to all the SLE patients who have fertility intention and focus more on those who have requirements for fertility.


Levocetirizine and rupatadine in chronic idiopathic urticaria.
Chronic idiopathic urticaria (CIU) is a common dermatological condition. Its pathogenesis involves mainly histamine and also other mediators, including platelet-activating factor (PAF) and tumor necrosis factor-α (TNF-α). In the absence of an exact etiology, H1 -antihistaminics are the mainstay of treatment. Levocetirizine is widely prescribed for CIU. Rupatadine, a newer antihistaminic, has PAF receptor antagonist activity and has shown anti-TNF-α activity in vitro. These additional anti-inflammatory effects may improve its efficacy. This study was conducted to compare the efficacy and safety of rupatadine and levocetirizine, respectively, in CIU patients. A prospective, open, comparative, randomized study was conducted in 100 patients, of whom 50 were treated with levocetirizine and 50 were treated with rupatadine. Efficacy parameters used were urticarial activity score (UAS) and Dermatology Life Quality Index (DLQI) values. Safety was evaluated by monitoring for adverse drug reactions and by using the critical flicker fusion threshold (CFFT) test and a visual analog scale (VAS) at baseline, and at 2, 4, and 6 weeks. The mean UAS decreased to 0.10 in the levocetirizine group and to 0.38 in the rupatadine group. Patients in the levocetirizine group showed a more significant (P < 0.001) improvement, although symptoms improved in both groups. Significant reductions in mean DLQI scores were observed in both groups, but the decrease was statistically significant in the levocetirizine group (P < 0.05). Somnolence was the most common side effect in both groups. Patients in the levocetirizine group showed more psychomotor impairment based on the CFFT test. Findings on the VAS showed sedative effects in both groups (P < 0.05). Levocetirizine was found to be more efficacious than rupatadine in CIU patients, but both drugs caused mild sedation.


Regional differences in hospitalizations and cholecystectomies for biliary dyskinesia.
Published studies suggest that socioeconomic factors contribute to increasing cholecystectomy rates for biliary dyskinesia (BD). The aim of this study was to identify factors driving admissions and operations for BD by examining regional variability in hospitalizations and cholecystectomies for this disorder. Annual hospitalizations and cholecystectomy rates for biliary diseases were assessed using the State Inpatient Databases of the Agency for Healthcare Research and Quality based on diagnosis codes for biliary dyskinesia, cholecystolithiasis and cholecystitis. Annual admissions for BD varied nearly sevenfold among different states within the United States. Hospitalizations for gallstone disease and its complication showed less variability, differing 2-fold between states. Nearly 70% of admissions for BD and about 85% of admissions for gallstone disease resulted in cholecystectomies. Higher admission rates for BD were best predicted by high overall hospitalization rates, admission rate for gallstone disease and the physician workforce within a state. Cholecystectomy rates for BD were higher in states with low population density and high rates of cholecystectomy for gallstone disease. These data suggest that established medical practice patterns significantly contribute to the variability in admissions and operations for biliary dyskinesia. The findings also indicate that lower thresholds for operative interventions are an important determinant in the approach to this disorder. Considering the benign course of functional illnesses, the bar for surgical interventions should be raised rather than lowered; in addition active conservative treatment options should be developed for these patients.


[Interferon responses of various populations of lymphocytes of inbred mice with various degrees of sensitivity to the western equine encephalitis virus].
The sensitivity of mice of three lines: CBA, BALB/C, and C57BL/6 (males aged greater than or equal to 4-5 and one week) to peripheral inoculation with Western equine encephalomyelitis (WEE) virus was studied. The C57BL/6 line was found to be the most and CBA the least sensitive. The first generation hybrids between these lines are intermediate in their sensitivity to WEE virus. A correlation was established between the increased sensitivity to WEE virus of C57BL/6 mice and the defect of the interferon system in these mice manifested by the extremely low capacity of their thymocytes for production of beta and alpha-interferons, as well as by a significant decrease of interferon responses of splenocytes to Newcastle disease virus, L-1 (alpha-interferon), lafarin, beta-interferon, concanaxalin-A (alpha-interferon) after immunization with antigens of different origin.


Nitrogen acquisition strategy and its effects on invasiveness of a subtropical invasive plant.
Preference and plasticity in nitrogen (N) form uptake are the main strategies with which plants absorb soil N. However, little effort has been made to explore effects of N form acquisition strategies, especially the plasticity, on invasiveness of exotic plants, although many studies have determined the effects of N levels (e.g. N deposition). To address this problem, we studied the differences in N form acquisition strategies between the invasive plant Solidago canadensis and its co-occurring native plant Artemisia lavandulaefolia, effects of soil N environments, and the relationship between N form acquisition strategy of S. canadensis and its invasiveness using a 15N-labeling technique in three habitats at four field sites. Total biomass, root biomass, and the uptakes of soil dissolved inorganic N (DIN) per quadrat were higher for the invasive relative to the native species in all three habitats. The invader always preferred dominant soil N forms: NH4 + in habitats with NH4 + as the dominant DIN and NO3 - in habitats with NO3 - as the dominant DIN, while A. lavandulaefolia consistently preferred NO3 - in all habitats. Plasticity in N form uptake was higher in the invasive relative to the native species, especially in the farmland. Plant N form acquisition strategy was influenced by both DIN levels and the proportions of different N forms (NO3 -/NH4 +) as judged by their negative effects on the proportional contributions of NH4 + to plant N (f NH4 +) and the preference for NH4 + (β NH4 +). In addition, total biomass was positively associated with f NH4 + or β NH4 + for S. canadensis, while negatively for A. lavandulaefolia. Interestingly, the species may prefer to absorb NH4 + when soil DIN and/or NO3 -/NH4 + ratio were low, and root to shoot ratio may be affected by plant nutrient status per se, rather than by soil nutrient availability. Our results indicate that the superior N form acquisition strategy of the invader contributes to its higher N uptake, and therefore to its invasiveness in different habitats, improving our understanding of invasiveness of exotic plants in diverse habitats in terms of utilization of different N forms.


[The treatment of parapneumonic effusions and pleural empyemas].
Pleural effusions of infectious origin usually present as a complication of pneumonia, or, more rarely, of thoracic surgical procedures. Treatment is based upon the clinical picture, the appearance of the pleural fluid, on certain laboratory parameters, and upon the success of therapeutic interventions. The initial antibiotic regimen should cover the causative organisms that may empirically be expected in the individual setting of the patient. Similar to the situation in pneumonias, the spectrum of organisms in community-acquired effusions or empyemas differs substantially from that in hospital-acquired pleural infections. The management of pleural empyemas should follow an interdisciplinary strategy which involves the pulmonologist and the thoracic surgeon. The single most important intervention is the early and effective drainage of the pleural cavity. Loculated effusions that do not promptly improve after drainage can additionally be treated by a trial of intrapleural fibrinolysis for a period of approximately three days. However, the precise role of fibrinolytics in the setting of complicated pleural effusions and empyemas remains to be better defined. Early definitive surgical treatment, preferentially by video-assisted thoracoscopic surgery (VATS), should be the goal in all patients who do not promptly respond to drainage and/or intrapleural fibrinolytic therapy and who qualify for a surgical intervention.


A comparative study of six European databases of medically oriented Web resources.
The paper describes six European medically oriented databases of Web resources, pertaining to five quality-controlled subject gateways, and compares their performance. The characteristics, coverage, procedure for selecting Web resources, record structure, searching possibilities, and existence of user assistance were described for each database. Performance indicators for each database were obtained by means of searches carried out using the key words, "myocardial infarction." Most of the databases originated in the 1990s in an academic or library context and include all types of Web resources of an international nature. Five databases use Medical Subject Headings. The number of fields per record varies between three and nineteen. The language of the search interfaces is mostly English, and some of them allow searches in other languages. In some databases, the search can be extended to Pubmed. Organizing Medical Networked Information, Catalogue et Index des Sites Médicaux Francophones, and Diseases, Disorders and Related Topics produced the best results. The usefulness of these databases as quick reference resources is clear. In addition, their lack of content overlap means that, for the user, they complement each other. Their continued survival faces three challenges: the instability of the Internet, maintenance costs, and lack of use in spite of their potential usefulness.


[Tuberculosis in Iceland. 1976].
Because of signs of tuberculous lesions in old skeletons it can be stated with certainty that tuberculosis has occurred in the country shortly after the settlement. From that time and up to the seventeenth century, little or nothing is known about the occurrence of the disease. A few preserved descriptions of diseases and deaths indicate that tuberculosis has existed in the country before the advent of qualified physicians in 1760. On the basis of papers and reports from the first physicians and the first tuberculosis registers the opinions is set forth that the disease has been rare up to the latter part of the nineteenth century. During the two last decades of that century the disease began to spread more rapidly and increased steadily up to the turn of the century. Although reporting of the disease was started in the last decade of the nineteenth century the reporting was first ordered by law with the passage of the first tuberculosis Act in the year 1903. With this legislation official measures for tuberculosis control work really started in the country. The first sanatorium was built in 1910. In 1921 the tuberculosis Act was revised and since then practically all the expenses for the hospitalization and treatment of tuberculous cases has been defrayed by the state. In the year 1935 organized tuberculosis control work was begun and a special physician appointed to direct it. From then on systematic surveys were made, partly in health centers i.e. tuberculosis clinics, which were established in the main towns, and partly by means of transportable X ray units in outlying rural areas of the country. In 1939 the tuberculosis Act was again revised with special reference to the surveys and the activities of the tuberculosis clinics. This act is still in force. Some items of it are described. The procedure of the surveys and the methods of examination are described. The great majority of subjects were tuberculin tested and all positive reactors X rayed. Furthermore, X ray examination was made in all cases where tuberculin examination had not been made or was incomplete. The negative reactors were not X rayed. The tuberculin tests were percutaneous, cutaneous and intracutaneous. The X ray examination during the first years was performed by means of fluoroscopy and roentgenograms were made in all doubtful cases. In 1945 when the survey of the capital city of Reykjavík was made and comprised a total of 43,595 persons photoroentgenograms were made. After 1948 only this method together with tuberculin testing was used in all the larger towns in the country. During the period 1940-1945 such surveys were carried out in 12 medical districts, or parts thereof and included 58,837 persons or 47 percent of the entire population. The attendance in these surveys ranged from 89.3 percent to 100 percent of those considered able to attend. In the capital city, Reykjavík, the attendance was 99.32 percent. The course and prevalence of tuberculosis in Iceland from 1911 to 1970 are traced on the basis of tuberculosis reporting registers, mortality records which were ordered by law in 1911, tuberculin surveys and post mortem examinations. The deficiencies of these sources are pointed out. Since 1939 the morbidity rates are accurate. The number of reported cases of tuberculosis increases steadily up to the year 1935, when 1.6 percent of the population is reported to have active tuberculosis at the end of that year. Thereafter it begins to decline gradually the first years but abruptly in 1939, then without doubt because of the revision of the tuberculosis legislation and more exact reporting regulations. After that year the fall is almost constant with rather small fluctuations as regards new cases, relapses and total number of reported cases remaining on register at the end of each year. In 1950 the new cases are down to 1.6 per thousand and at the end of the year the rate for those remaining on register is 6.9 per thousand. In the year 1954 there is a noteworthy drop both in new cases and the total number reported, doubtless because of the new specific medication which began in 1952. In 1960 the new cases are down to 0.4, relapses 0.2 and the rate for those remaining on register at the end of the year 2.4 per thousand. And in 1970 the rate for the same categories are: new 0.2, relapses 0.06, and remaining at the end of the year 0.5 per thousand. At the beginning of the period, when registration of deaths was initiated, tuberculosis mortality was found to be about 150 per 100,000 population. During the next two decades it increases, irregularly but persistently, to reach a peak of 217 in 1925. It remained high for the next seven years, dropped suddenly to 154 in 1933, and then, apart from a slight temporary increase during the years of the second world war, continued to fall rapidly reaching 20 per 100,000 population in 1950. In the period from 1930-50 the tuberculous death rate thus dropped a little over 90 percent. In the year 1952, when specific tuberculosis medical treatment was initiated (streptomycin, isoniazid and PAS) the death rate dropped to 14 per 100,000 population and the next year further down to 9 and since 1956 it never exceeded 5 per 100,000. From the year 1962 the tuberculosis mortality has never been over 2 per 100,000 population. The mortality rates have been broken down to reveal the role of age and sex specific death rates over some selected five year periods. Also the rates are shown according to different forms of the disease, pulmonary, meningeal and other forms. The highest proportionate mortality (60%) was observed in the 15-19 year age group between 1926 and 1930. From 1911 to 1930 tuberculous meningitis caused a remarkably high number of deaths, fluctuating between 20 and 50 per 100,000 population. Since 1956 not a single death from this form of the disease has occurred. Up to that year the highest meningitis death-rate consistently occurred in infancy and early childhood. Sex-specific tuberculosis death rates indicate that in every age-group the disease is more dangerous to women. Between 1941 and 1945, when the combined mortality-rate began to drop sharply, it was the rate for the males, which was first affected. Due to the very steep decline in tuberculosis mortality especially from 1952 tuberculosis mortality figures can no longer be considered the right criterion for the spread and course of the disease. The infection and morbidity rates are from then on the best measures of the prevalence and course of the disease. Tuberculosis infection-rates obtained through tuberculin testing on a comparatively broad scale, especially in school children 7-13 years of age, show a progressive reduction in tuberculosis infection in the country as a whole. These tuberculin surves on school children were initiated by the district health officers in the second decade of the century and therefore now extend over 60 years. The procedure of the tuberculin surveys and the methods used are mentioned. The shortcomings of these surveys and their importance are discussed. The value of the surveys is considered doubtful as long as the examinations are performed without any guidance or coordination. About the year 1930 the total percentage tuberculin tested in the age group 7-13 years was a little over 10 percent. In the year 1935 the director of tuberculosis control sent all the health officers instructions on how to perform the tuberculin testing together with some encouragement to perform such surveys. That year about 43 percent of the 7-13 years population was tested and in 1945 the percentage was 75. Between 1965 and 1970 the attendance percentage was 85. The tested 7-13 years age group showed in 1935 26.1 percent positive reaction, in 1945 10.1 percent, in 1955 5.3 percent and in 1970 0.7 percent. In 1970 0.2 percent of the 7 years old children reacted positively and 1.1 percent of those 13 years of age. the decline of the infection rate in this age group is remarkable. The very few BCG vaccinated children were excluded from the surveys. In the tuberculosis surveys made in the years 1940-1945, which covered 12 medical districts or parts thereof, extensive tuberculin examinations were performed. The results of these surveys showed that the infection rate was higher among male adults than females. This difference was notable after the age of 15 and especially in isolated and thinly populated rural districts. In urban and more thickly populated rural districts the infection rate was much higher. BCG vaccination was first used in Iceland in 1945. Only few persons were vaccinated in the first two years. In 1948 a systematic vaccination was proposed in the country to supplement the tuberculosis-control plan. The vaccination was particularly meant for the age group 12-29 where the risk of infection appeared to be greatest. However, at the end of the year 1950 a total of only about 6,900 persons had been vaccinated mostly groups of school children, young adults and contacts of tuberculosis cases. Most of the children and adults were born between the years 1929 and 1936 but in none of these years did the vaccination exceed 15 percent of those born in any one of the years concerned. Because of the rapid decline in the tuberculosis infection rate, morbidity and mortality in the country this vaccination plan was abandoned and changed at the end of the year 1950. After that only few groups of people were vaccinated, i.e. tuberculosis contacts, medical students, student nurses, adults studying abroad and persons who asked for vaccination. Between 1950 and 1970 only about 7,000 people have been vaccinated. So the total number of BCG vaccinations up to the end of 1970 has not exceeded 14,000 in the country. Therefore it seems most unlikely that the relatively few BCG vaccinations, given in recent years can be expected to have had much influence in speeding up the downward trend of the disease in the country. (ABSTRACT TRUNCATED)


New Closures for More Precise Modeling of Landau Damping in the Fluid Framework.
Incorporation of kinetic effects such as Landau damping into a fluid framework was pioneered by Hammett and Perkins, by obtaining closures of the fluid hierarchy, where the gyrotropic heat flux fluctuations or the deviation of the fourth-order gyrotropic fluid moment are expressed through lower-order fluid moments. To obtain a closure of a fluid model expanded around a bi-Maxwellian distribution function, the usual plasma dispersion function Z(ζ) that appears in kinetic theory or the associated plasma response function R(ζ)=1+ζZ(ζ) has to be approximated with a suitable Padé approximant in such a way that the closure is valid for all ζ values. Such closures are rare, and the original closures of Hammett and Perkins are often employed. Here we present a complete mapping of all plausible Landau fluid closures that can be constructed at the level of fourth-order moments in the gyrotropic limit and we identify the most precise closures. Furthermore, by considering 1D closures at higher-order moments, we show that it is possible to reproduce linear Landau damping in the fluid framework to any desired precision, thus showing convergence of the fluid and collisionless kinetic descriptions.


Evolutionary Hysteresis and Ratchets in the Evolution of Periodical Cicadas.
It has been previously hypothesized that the perfectly synchronized mass emergence of periodical cicadas (Magicicada spp.) evolved as a result of a switch from size-based to age-based emergence. In the former case, cicada nymphs emerge immediately (at the first opportunity) on reaching maturity, whereas in the latter case, nymphs wait in order to emerge at a specific age. Here we use an individual-based model to simulate the cicada life cycle and to study the evolution of periodicity. We find that if age-based emergence evolves in a constant abiotic environment, it typically results in a population that is protoperiodic, and synchronous emergence of the whole population is not achieved. However, perfect periodicity and synchronous emergence can be attained, if the abiotic environment changes back and forth between favorable and unfavorable conditions (hysteresis). Furthermore, once age-based emergence evolves, generally it can only be invaded by other age-based emergence strategies with longer cycle lengths (evolutionary ratchet). Together, these mechanisms promote the evolution of long periodic life cycles and synchronous emergence in the Magicicada. We discuss how our results connect to previous theories and recent phylogenetic studies on Magicicada evolution.


Circadian rhythm in the torque developed by elbow flexors during isometric contraction. Effect of sampling schedules.
Time-dependent changes in elbow flexion torque have been documented according to two different sampling schedules. Seven physical education students took part in the first series of experiments, and 7 other similar subjects in the second. In both sets of experiments, the subjects performed isometric contractions: maximal and submaximal at 90 degrees in the first experiments and maximal at different angular positions in the second. After a 30-minute rest period, the torque developed was measured at 00:00, 06:00, 09:00, 12:00, 15:00, 18:00, and 21:00 h on the day of the experiment. These subjects remained in the laboratory for 24 h. In the second series of experiments, the torque developed was measured at 01:00, 05:00, 09:00, 13:00, 17:00, and 21:00 h over the subsequent 6 days with only one test session per day. In this case, there was an interval of 20 h between two successive test sessions. In the first experiment, a significant time-of-day effect was observed for the torque of the elbow flexors under isometric conditions with an acrophase at 17:58 h. The 24 h normalized mean score was 92.85% with an amplitude of 7.63% of the daily mean. In the second series of experiments, there was evidence of a circadian rhythm in the torque developed by the elbow flexors at every angle position, especially at 90 degrees, the angle investigated in the first set of experiments. The peak torque was calculated to have occurred at 17:55 h. The amplitude of the rhythm was equal to 6.99% of the daily mean. There were no statistically significant differences in the characteristics of the circadian rhythm observed between the two experimental designs. We concluded that an experiment extending over several days could be employed to evaluate circadian rhythms in muscular activity reliably.


Negative-pressure Wound Therapy for Periocular Necrotizing Fasciitis.
Periocular necrotizing fasciitis is a rare, but potentially blinding, or even fatal disease. The authors report a case of a 44-year-old man who presented with quiescent bilateral periocular and facial necrotizing fasciitis. The patient was treated with antibiotics and surgical debridement, followed by negative-pressure wound therapy (NPWT), until the wound bed was thought to be healthy enough to support bilateral upper eyelid full-thickness skin grafts. NPWT appeared to decrease local edema; speed reperfusion and granulation tissue formation; and served to stabilize the skin grafts against the wound bed, while not causing any ocular complications. NPWT can be a safe and effective adjunct treatment for periocular necrotizing fasciitis.


Gene and drug landing page aggregator.
Many biological and biomedical researchers commonly search for information about genes and drugs to gather knowledge from these resources. For the most part, such information is served as landing pages in disparate data repositories and web portals. The Gene and Drug Landing Page Aggregator (GDLPA) provides users with access to 50 gene-centric and 19 drug-centric repositories, enabling them to retrieve landing pages corresponding to their gene and drug queries. Bringing these resources together into one dashboard that directs users to the landing pages across many resources can help centralize gene- and drug-centric knowledge, as well as raise awareness of available resources that may be missed when using standard search engines. To demonstrate the utility of GDLPA, case studies for the gene klotho and the drug remdesivir were developed. The first case study highlights the potential role of klotho as a drug target for aging and kidney disease, while the second study gathers knowledge regarding approval, usage, and safety for remdesivir, the first approved coronavirus disease 2019 therapeutic. Finally, based on our experience, we provide guidelines for developing effective landing pages for genes and drugs. GDLPA is open source and is available from: https://cfde-gene-pages.cloud/. Supplementary data are available at Bioinformatics Advances online.


Out-of-hospital cardiac arrest in denver, colorado: epidemiology and outcomes.
The annual incidence of out-of-hospital cardiac arrest (OOHCA) in the United States is approximately 6 per 10,000 population and survival remains low. Relatively little is known about the performance characteristics of a two-tiered emergency medical services (EMS) system split between fire-based basic life support (BLS) dispersed from fixed locations and hospital-based advanced life support (ALS) dispersed from nonfixed locations. The objectives of this study were to describe the incidence of OOHCA in Denver, Colorado, and to define the prevalence of survival with good neurologic function in the context of this particular EMS system. This was a retrospective cohort study using standardized abstraction methodology. A two-tiered hospital-based EMS system for the County of Denver and 10 receiving hospitals were studied. Consecutive adult patients who experienced nontraumatic OOHCA from January 1, 2003, through December 31, 2004, were enrolled. Demographic, prehospital arrest characteristics, treatment data, and survival data using the Utstein template were collected. Good neurologic survival was defined by a Cerebral Performance Categories (CPC) score of 1 or 2. During the study period, 1,985 arrests occurred. Of these, 715 (36%) had attempted resuscitation by paramedics and constitute our study sample. The median age was 65 years (interquartile range = 52-78 years), 69% were male, 41% had witnessed arrest, 25% had bystander cardiopulmonary resuscitation (CPR) performed, and 30% had ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) as their initial rhythm. Of the 715 patients, 545 (76%) were transported to a hospital, 223 (31%) had return of spontaneous circulation (ROSC), 175 (25%) survived to hospital admission, 58 (8%) survived to hospital discharge, and 42 (6%, 95% confidence interval [CI] = 4% to 8%) had a good neurologic outcome. Out-of-hospital cardiac arrest survival in Denver, Colorado, is similar to that of other United States communities. This finding provides the basis for future epidemiologic and health services research in the out-of-hospital and ED settings in our community.


Eco-effective design and evidence-based design: perceived synergy and conflict.
Eco-effective design (EED) and evidence-based design (EBD) are two powerful trends currently shaping healthcare architecture. EED addresses whether/how the design and operation of buildings improve ecological value and enhance human health. EBD addresses whether/how the design and operation of buildings support positive health outcomes in the built environment through a growing collection of solutions informed by research and practical knowledge. The primary hypothesis of this study was that EBD and EED are compatible approaches to health facility design, especially when addressing the impact of the environment on human health. To explore this hypothesis, healthcare facility administrators were surveyed regarding their perceptions of the relationship between EED and EBD. Input from focus groups and EED and EBD experts was used to formulate the administrator questionnaire. The study concluded that the relationship between EED and EBD typically was synergistic.


[Difficulties in Caring for Psychiatric Patient as Experienced by Non-Psychiatric Nurses].
The purpose of this study was to identify non-psychiatric nurses' difficulties in caring for patients with mental illness. Data were collected from eighteen general medical-surgical nurses working at a university hospital in Seoul, Korea. This study involved two focus group discussions and three in-depth individual interviews. All interviews were recorded and transcribed as they were spoken, and data were analyzed using qualitative content analysis. General medical-surgical nurses experienced difficulties in 3 categories, 9 subcategories, 27 codes. The three categories were 'nurse' related factors, 'patient' related factors, 'resource' related factors. The nine categories were 'unpreparedness', 'nursing barriers due to stigma', 'undervaluing and avoidance of psychiatric nursing', 'eroding into the trap of a vicious cycle', 'facing unapproachable patients', 'dealing with unhelpful family members', 'burdening already overburdened staff', 'obstructive environment', and 'isolation of staff with heavy responsibilities'. The results of this study indicate the need to develop psychiatric mental health education programs for non-psychiatric nurses. Education about psychiatric mental health and support from institutions for non-psychiatric nurses can reduce their negative attitude toward psychiatric patients and difficulties in caring for psychiatric patients.


Cortical processing of near-threshold tactile stimuli in a paired-stimulus paradigm--an MEG study.
In the present magnetoencephalography study, we applied a paired-stimulus paradigm to study the weak cortical responses evoked by near-threshold tactile prime stimuli by means of their attenuating effect on the cortical responses evoked by subsequently applied above-threshold test stimuli. In stimulus pairs with adequate interstimulus intervals (ISIs), the extent of test stimulus response attenuation is related to the amplitude of prime stimulus responses, and the duration of the attenuating effect indicates how long memory traces of a prime stimulus reside in cortical areas. We hypothesized that the attenuation of test stimulus responses, studied for ISIs of 30, 60 and 150 ms, would provide insight into the temporal dynamics of near-threshold stimulus processing in primary (SI) and secondary somatosensory cortex (SII), and reveal differences in response amplitude due to conscious perception. Attenuation of test stimulus responses in SI was observed for ISIs up to 60 ms, whereas in SII the effect outlasted the ISI of 150 ms. Differences due to conscious perception of the near-threshold stimuli were only observed in SII with stronger attenuation for perceived than for missed near-threshold stimuli. Applying this indirect approach to near-threshold stimulus processing, we could show that the extent and duration of response attenuation is related to prime stimulus processing and differential temporal and functional characteristics of near-threshold stimulus information processing in SI and SII: transient processing of basic stimulus information not sufficient for conscious perception in SI and long-lasting activations involving conscious perception in SII.


[Corrigendum] Knockdown of lncRNA HNF1A-AS1 inhibits oncogenic phenotypes in colorectal carcinoma.
Following the publication of the article, the authors noted an error associated with the presentation of Fig. 3B. This Figure part showed the cell cycle analysis as determined by flow cytometry of HT29 cells transfected with either a HNF1A-AS1-specific siRNA or a negative control siRNA at 48 h post-transfection. An error was made in the compilation of this Figure, and the same data were inadvertently selected to represent the cell cycle analysis of both the HT29-SI and the HT29-NC cells (i.e., the data relating to the HT29-NC cells were included in the Figure twice). A corrected version of Fig. 3 is shown on the next page. Note that this correction affects neither the interpretation of the data nor the reported conclusions of this work. The authors all agree to this Corrigendum, and regret that this error went unnoticed during the proofs correction stage. They also wish to thank the Editor for allowing them the opportunity to publish this Corrigendum, and regret any inconvenience this error has caused. [the original article was published in Molecular Medicine Reports 16: 4694-4700, 2017; DOI: 10.3892/mmr.2017.7175].


Change and stability: use of complementary and alternative medicine in Israel: 1993, 2000 and 2007.
Complementary and alternative health care has gained increasing popularity in Western societies in recent years. The objective of the article is to explore cross-sectional variations and temporal changes in the patterns of complementary and alternative medicine (CAM) consultations in Israel in 1993, 2000 and 2007. Interviews were conducted with 2003 respondents in 1993, 2505 in 2000, and 752 in 2007, using identical questions. The samples represented the Israeli Jewish urban population aged 45-75 in the respective years. The rate of use of CAM during the previous year increased from 6% in 1993, to 10% in 2000 and reached 12% in 2007. Women and highly educated persons have been significantly and consistently more likely to use CAM. Among the users, homeopathy, acupuncture and reflexology are the main types of CAM used. Lower back pain became the leading problem for which care was sought. A significant proportion of the users continue to use conventional medicine concurrently, and an increasing share was referred to CAM by their physician. Past good experience has become a major reason for CAM use. Between 1993 and 2007, CAM use in the Israeli urban Jewish population aged 45-75 years increased significantly. As in other countries CAM grew from an infant industry and entered the mainstream of health care. The evidence reported here highlights the urgent need for the design of health and social policies aiming to achieve more effective integration between CAM and conventional medicine.


Does performance-based financing increase value for money in low- and middle- income countries? A systematic review.
Governments of low- and middle-income countries (LMICs) are widely implementing performance-based financing (PBF) to improve healthcare services. However, it is unclear whether PBF provides good value for money compared to status quo or other interventions aimed at strengthening the healthcare system in LMICs. The objective of this systematic review is to identify and synthesize the existing literature that examines whether PBF represents an efficient manner of investing resources. We considered PBF to be efficient when improved care quality or quantity was achieved with equal or lower costs, or alternatively, when the same quality of care was achieved using less financial resources. A manual search of the reference lists of two recent systematic reviews on economic evaluations of PBF was conducted to identify articles that met our inclusion and exclusion criteria. Subsequently, a search strategy was developed with the help of a librarian. The following databases and search engines were used: PubMed, EconLit, Google Scholar and Google. Experts on economic evaluations were consulted for validation of the selected studies. A total of seven articles from five LMICs were selected for this review. We found the overall strength of the evidence to be weak. None of the articles were full economic evaluations; they did not make clear connections between the costs and effects of PBF. Only one study reported using a randomized controlled trial, but issues with the randomization procedure were reported. Important alternative interventions to strengthen the capacities of the healthcare system have not been considered. Few studies examined the costs and consequences of PBF in the long term. Important costs and consequences were omitted from the evaluations. Few LMICs are represented in the literature, despite wide implementation. Lastly, most articles had at least one author employed by an organization involved in the implementation of PBF, thereby resulting in potential conflicts of interest. Stronger empirical evidence on whether PBF represents good value for money in LMICs is needed.


Early and late phases of ocular anaphylaxis in actively immunized guinea pigs.
A model of ocular anaphylaxis with distinct early- and late-phase components was studied in actively immunized guinea pigs. Twenty guinea pigs were injected with dinitrophenylated (DNP) bovine gamma globulin emulsified in Freund's complete adjuvant and challenged topically with di-DNP-lysine. Clinical signs were monitored over a 48 h period. An early-phase reaction (EPR) characterized by conjunctival edema, conjunctival erythema, lid swelling, and lid redness was observed. This reaction peaked at 0.5 h after challenge and subsided to a low point at 3-4 h. Subsequently, a second episode of lid swelling and lid redness was observed at 4-8 h. All animals in both groups exhibited an EPR. In addition, 75% of the animals underwent an EPR and an LPR. No animals exhibited an isolated LPR. Of the animals that underwent a dual response, 47% were biphasic, 6% were prolonged and 47% were multiphasic. The development of an active model of ocular anaphylaxis exhibiting both EPR and LPR components will enable studies of mechanisms which regulate the frequency and magnitude of these ocular allergic responses.


Thoracic epidural analgesia for radical cystectomy improves bowel function even in traditional perioperative care: a retrospective study in eighty-five patients.
Radical cystectomy is associated with significant morbidity and mortality due to complex surgery and comorbidities associated with advanced age of patients. In contrast to the surgery, which is clearly the procedure of choice for patients with invasive bladder cancer, the opti- mal anesthesiologic method is still under debate. Therefore, we retrospectively analyzed 85 patients having undergone radical cystectomy at our institution, either under combined epidural-general anesthesia (CEGA) or opioid based general anesthesia (GA). The intraoperative blood loss was significantly lower in CEGA group (497.37 ± 354.13) than in GA group (742.31 ± 403.69; p = 0.006), due to induced hypotension. Consequently, blood transfusion requirements were lower in CEGA group (107.20 ± 263.92) than in GA group (388.18 ± 321.32; p = 0.001). The incidence of postoperative ileus was also lower in CEGA group (p = 0.024). There was no difference in analgesic efficacy, but a trend towards lower incidence of venous thrombosis and infection was noticed. The results of our study suggest that epidural anesthesia might have specific advantages in patients undergoing radical cystectomy.


A practical protocol for dynamic modelling of activated sludge systems.
Use of dynamic simulation models has become standard practice in The Netherlands. Since the introduction around 5 years ago more then 100 full scale wastewater treatment plants have been modelled. Initially very different approaches have been used varying in calibration approach, amount of sampling and time investment. Based on the accumulated practical experiences the Dutch Foundation of Applied Water Research STOWA has stimulated the development of a protocol to aid in the set-up and calibration of models for full scale wastewater treatment plants. Herein the aim was to develop a protocol, which in practice was easy to use, minimising time and costs effort, but give a reliable and useable method. In this paper this protocol is briefly described.


Determination of renal clearance of neopterin by a pharmacokinetic approach.
Pharmacokinetic modelling was used to determine the glomerular filtration rate and tubular secretion of neopterin, a marker for cellular immune activation. The method involves parameter identification employing the transient venous plasma concentration profiles of marker substances. By combined i.v. injection of neopterin and inulin which is excreted exclusively via glomerular filtration, neopterin was shown to be excreted in addition to glomerular filtration, by tubular secretion: clearance of inulin, 112 (S.D. 2.2) ml/liter; clearance of neopterin, 499 (S.D. 79.7) ml/min. A pilot experiment using in addition p-amino hippuric acid suggests that neopterin and p-amino hippuric acid may employ the same carrier system for tubular secretion.


A composite chiral pair of rotational bands in the odd-A nucleus 135Nd.
High-spin states in 135Nd were populated with the 110Pd(30Si,5n)135Nd reaction at a 30Si bombarding energy of 133 MeV. Two DeltaI=1 bands with close excitation energies and the same parity were observed. These bands are directly linked by DeltaI=1 and DeltaI=2 transitions. The chiral nature of these two bands is confirmed by comparison with three-dimensional tilted axis cranking calculations. This is the first observation of a three-quasiparticle chiral structure and establishes the primarily geometric nature of this phenomenon.


Statistical relationship between ultrasound echo envelope and envelope peak.
This study shows that the amplitude information of ultrasound echoes is carried mainly by the envelope peaks (EPs). It is first shown that the EPs in an A-line represent the maximum number of independent amplitude data. It is then demonstrated that the entire envelope could be approximately reconstructed from the EPs. Finally, using the echo data from a tissue-mimicking phantom, it is found that there are no significant differences among the attenuation coefficients estimated from the EPs, the original envelope samples, and the reconstructed envelope samples. The results of this study indicate that, in the time domain, the attenuation coefficient can be most efficiently estimated from the envelope peaks.


FISSR-PCR: a simple and sensitive assay for highthroughput genotyping and genetic mapping.
The recently developed Inter-Simple Sequence Repeat PCR (ISSR-PCR) or microsatellite primed PCR or Simple Sequence Repeat (SSR)-Anchored PCR technique detects polymorphic markers in a wide variety of genomes. Usually the ISSR primers are either 5' end-labeled with gamma[32P]ATP or one of the alpha[32P] labeled dNTPs is added to the PCR reaction and the PCR products are resolved on PAGE and autoradiographed. Alternatively, cold PCR products are resolved on agarose gel electrophoresis. In the present study, we show that informativity, sensitivity and speed of the ISSR-PCR can be substantially enhanced by adding fluorescent nucleotide in the PCR reaction followed by resolution of PCR products on an ABI 377 automated sequencer. The informativeness, measured as a number of detectable amplified fragments, was two-fold higher and the quantity of required template DNA is two-fold lower than the regular ISSR-PCR. We have termed this method as FISSR-PCR and show its usefulness in generating large number of species and varietal specific markers in plants, insects, parasites of insects and human and various infectious organisms. Further, we show that the FISSR markers are inherited and segregated in Mendelian fashion as demonstrated on a panel of 99 F2 offspring derived from a cross of two divergent silkworm strains. The FISSR-PCR marker assay could be a method of choice for large scale screening of varieties/cultivars and highthroughput genotyping in mapping of genomes where microsatellite information is scanty or absent.


PHYSIOLOGICAL STRESS AND COLOR POLYMORPHISM IN THE INTERTIDAL SNAIL NUCELLA LAPILLUS.
The intertidal snail Nucella lapillus exhibits considerable variation in shell color both within and between populations differentially exposed to wave action. Populations from high-wave-energy shores tended to be highly polymorphic and were dominated by pigmented morphs (especially brown), while those at more sheltered locations exhibited less polymorphism and were predominantly white. Field and laboratory experiments were conducted to determine the role of physiological stress and selective predation in maintaining the observed distribution of color morphs. The results demonstrated that 1) physiological stress from high temperature and desiccation during periods of tidal emersion was greater on protected shores, 2) under similar natural conditions, brown morphs heated up faster, attained higher temperatures, desiccated more rapidly, and suffered greater mortality than did white morphs, and 3) when pairs of brown and white morphs were tethered intertidally there was virtually no mortality of either morph on the exposed shore or in shaded microhabitats on the protected shore, but brown morphs suffered much greater mortality in sunny microhabitats on the protected shore. These findings demonstrate that the interpopulation variation in shell color of N. lapillus is in part a response to a selective gradient in physiological stress. Selection for crypsis by visually hunting predators did not appear to play a prominent role; however, only adults were considered, and the predation experiments were conducted in the fall before shorebirds that prey on whelks had arrived from their summer feeding grounds. Further experimentation to quantify the effects of visual predators such as birds and fish, particularly on juvenile snails, is necessary to assess adequately the importance of predation.


A comparative risk assessment for Listeria monocytogenes in prepackaged versus retail-sliced deli meat.
Deli meat was ranked as the highest-risk ready-to-eat food vehicle of Listeria monocytogenes within the 2003 U.S. Food and Drug Administration and U.S. Department of Agriculture, Food Safety and Inspection Service risk assessment. The comparative risk of L. monocytogenes in retail-sliced versus prepackaged deli meats was evaluated with a modified version of this model. Other research has found that retail-sliced deli meats have both higher prevalence and levels of L. monocytogenes than have product sliced and packaged at the manufacturer level. The updated risk assessment model considered slicing location as well as the use of growth inhibitors. The per annum comparative risk ratio for the number of deaths from retail-sliced versus prepackaged deli meats was found to be 4.89, and the per-serving comparative risk ratio was 4.27. There was a significant interaction between the use of growth inhibitors and slicing location. Almost 70% of the estimated deaths occurred from retail-sliced product that did not possess a growth inhibitor. A sensitivity analysis, assessing the effect of the model's consumer storage time and shelf life assumptions, found that even if retail-sliced deli meats were stored for a quarter of the time prepackaged deli meats were stored, retail-sliced product is 1.7 times more likely to result in death from listeriosis. Sensitivity analysis also showed that the shelf life assumption had little effect on the comparative risk ratio.


Amperometric determination of L-lactate based on entrapment of lactate oxidase on a transducer surface with a semi-permeable membrane using a SIRE technology based biosensor. Application: tomato paste and baby food.
Determination of dissolved L-lactate in tomato paste and baby food samples using a SIRE-based (sensors based on injection of the recognition element) biosensor is reported. The measuring principle is based on the use of a small amount of enzyme, which is injected into an internal delivery flow system and held in direct spatial contact with the amperometric transducer by the use of a semipermeable membrane. Measurements are based upon the reversible enzymatic conversion of L-lactate to pyruvate and hydrogen peroxide by lactate oxidase. Differential measurements are performed in which the samples are measured in the presence and absence of enzyme allowing for control over matrix interferences present in crude samples. The linear range investigated for the determination of L-lactate in tomato paste and baby food was 0-0.1 mM using a lactate oxidase concentration of 22 U/mL. Samples were diluted with buffer prior to biosensor measurements. The L-lactate concentrations of the tomato paste and baby food were determined to be 1.02 +/- 0.02 mM and 2.51 +/- 0.10 mM, respectively, using the standard addition method. The repeatability for tomato paste and baby food measurements was 2.5% (RSD, n = 15) and 4.0% (RSD, n = 15) and the reproducibility was 13.0% (RSD, n = 45) and 3.0% (RSD, n = 45), respectively. The concentration of dissolved L-lactate can be used as a measure of freshness in the food industry. All biosensor measurements were compared with measurements from an established spectrophotometric assay (Boehringer Mannheim). It was found that the biosensor had good correlation with the spectrophotometric method. The biosensor gave 12% higher values for the tomato paste measurements and 2.5% higher values for the baby food measurements. However, a distinct advantage of the biosensor is that it can perform L-lactate measurements within 3 minutes, whereas the spectrophotometric assay requires a 35-minute measurement time.


Quality Characteristics of Reduced-Fat Emulsified Sausages Made with Yeast Mannoprotein Enzymatically Prepared with a β-1,6-glucanase.
Mannoproteins, as yeast polysaccharides, have been utilized in food the industry as dietary fibers, emulsifying agents or fat replacers. Mannoprotein MP112, produced from yeast by enzymatic hydrolysis of myxobacterial β-1,6-glucanase GluM, exhibits excellent emulsifying properties in emulsion preparation. In this study, we aimed to examine the application of stable emulsion with the addition of mannoprotein MP112 (MP112 emulsion) to reduce the fat content of sausages. The addition of MP112 emulsion in emulsified sausages significantly reduced the fat content and increased the moisture and protein contents of emulsified sausages without the expense of their good sensory quality. Moreover, the textural properties of sausages were markedly improved with the higher hardness, chewiness and cohesiveness, especially in the 50-75% replacement ratio of MP112 emulsion. On the other hand, MP112 emulsion replacement of animal fat markedly improved the nutritional composition of emulsified sausages; they displayed a higher PUFA/SFA ratio and lower n-6/n-3 ratio due to their saturated fatty acids being replaced by poly-unsaturated fatty acids. Meanwhile, the oxidative stability of sausages was improved linearly, corresponding to the increased replacement ratio of MP112 emulsion. Our results show that mannoprotein-based emulsions could be used as potential fat alternatives in developing reduced-fat meat products.


Description of female of Titidius urucu Esmerio Lise, 1996 (Araneae: Thomisidae).
The genus Titidius Simon, 1895 belongs to the family Thomisidae Sundevall, 1833 and can be easily identified from the related genera Tmarus Simon, 1875 and Acentroscelus Simon, 1886 by the high carapace, anterior eye row straight and posterior eye row recurve-;pd in dorsal view, carapace smooth with moderate setation, abdomen longer than wide, legs long, slender and setose and clypeus vertical (Esmerio Lise 1996). It is currently composed of 20 species, all occurring in Brazil with exception of Titidius ignestii Caporiacco, 1947 from Guyana (World Spider Catalog 2017). Eight species are distributed in the Amazon region (Esmerio Lise 1996): T. caninde Esmerio Lise, 1996, T. gurupi Esmerio Lise, 1996, T. multifasciatus Mello-Leitão, 1929 and T. rubrosignatus (Keyserling, 1880) from Pará; T. galbanatus (Keyserling, 1880) from Amazonas and Pará; T. quinquenatus Mello-Leitão, 1929 and T. urucu from Amazonas; and T. rubescens Carporiacco, 1947 from Amazonas and Roraima.


Angiotensin II decreases cGMP levels in neuronal cultures from rat brain.
In previous studies we have determined that both cultured neuronal and astrocyte glial cells prepared from the hypothalamus and brain stem of 1-day-old rats contain specific receptors for angiotensin II (ANG II). Astrocyte glial receptors are coupled to inositol phospholipid hydrolysis, but there is little indication of the intracellular messengers or signal transduction mechanisms coupled to the neuronal ANG II receptors. In the present study, we have determined that ANG II decreases cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels in neuronal but not in astrocyte glial cultures. This effect is both time and concentration dependent and is inhibited by the ANG II-receptor antagonist [Sar1,Ile8]ANG II, showing the involvement of specific ANG II receptors. ANG II has no effects on particulate or soluble guanylate cyclase activities or on efflux of cGMP from neuronal cultures. However, the effects of ANG II on cellular cGMP content are abolished by pretreatment with the calcium channel blockers cadmium and nifedipine, and by the nonselective phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. These results suggest that calcium entry and possibly activation of a phosphodiesterase enzyme are involved in this ANG II-induced effect. This represents the first demonstration of a receptor-mediated effect of ANG II on an intracellular messenger in neuronal cultures. The functional role of cGMP as an intracellular messenger coupled to ANG II receptors in cultured neurons remains to be determined.


"AND" luminescent "reactive" molecular logic gates: a gateway to multi-analyte bioimaging and biosensing.
This review outlines examples that illustrate a recent and highly innovative concept in the field of (bio)molecular sensing, namely the simultaneous multi-analyte detection using "reactive" luminescent probes that are able to produce an optical signal only in response to multiple (bio)chemical inputs and through covalent chemical reactions with target (bio)analytes. Unlike conventional "AND" molecular logic gates based on supramolecular photochemical mechanisms, these unusual "smart" optical (bio)probes are suitable tools to track the rise and fall of a wider range of biologically relevant analytes, in complex media and with higher selectivity. The potential utility of this concept for in vivo molecular imaging and possible solutions to adapt the described luminogenic processes to far-red or NIR emitters are also discussed.


Risk factors of CMV infection in patients after umbilical cord blood transplantation: a multicenter study in China.
This retrospective study examined risk factors for cytomegalovirus (CMV) infection after umbilical cord blood transplantation (UCBT) and the impact of CMV infection on patient survival. In all 176 patients, plasma CMV DNA was negative prior to the transplantation, and examined twice a week for 100 d, and then once weekly for additional 300 d. Preemptive antiviral therapy (ganciclovir or foscarnet) was started in patients with >1,000/mL copies of CMV DNA but no full-blown CMV disease, and was discontinued upon two consecutive negative reports of blood CMV DNA test. The survival and risk factors for CMV infection or disease were examined using logistic regression. CMV infection developed in 71% (125/176) of the patients, with a median onset of 32 d. Four patients (2.3%) developed CMV disease. Neither the 5-year overall survival (OS) nor event-free survival (EFS) differed significantly in infected patients vs. those with no infection (59.4% vs. 64.8%, P=0.194; 53.4% vs. 59.1%, P=0.226). A stepwise multivariate analysis indicated an association of CMV infection with age, high-dose glucocorticoids, the number of transplanted CD34(+) cells, and the number of platelet transfusion, but not with gender, the conditioning regimen, and the day of neutrophil recovery and chronic graft-versus-host disease (cGVHD). CMV infection is very common after UCBT, but does not seem to affect long-term survival with preemptive antiviral treatment.


Self-grafting-induced epigenetic changes leading to drought stress tolerance in tomato plants.
Grafting is widely used as a method to increase stress tolerance in good fruiting lines of Solanaceae plants. However, little is known about how grafting, affects epigenetic modifications and leads to stress tolerance, especially within the same line. Here, we studied the effects of self-grafting in tomato plants on histone and DNA modifications and changes in gene expression related to drought stress. We found that at the three-leaf stage, 1 week after self-grafting, histone H3 K4 trimethylation and K27 trimethylation changes were observed in more than 500 genes each, and DNA methylation changes in more than 5,000 gene regions at the shoot apex compared to the non-grafted control. In addition, two weeks after the epigenomic changes, global expression changes continued to be observed at the shoot apex in several genes related to the metabolic process of nitrogen compounds, responses to stimulus, chromosome organization, cell cycle-related genes, and regulation of hormone levels. Finally, these grafted seedlings acquired remarkable drought tolerance, suggesting that epigenomic modifications during the wound-healing process mitigate stress tolerance in tomato plants.


Co-occurrence of restless legs syndrome and Parkin mutations in two families.
Recent studies have suggested an association between restless legs syndrome (RLS) and Parkinson's disease (PD). We present a large multigenerational family and a smaller family with RLS. A Parkin mutation was found in 10 of 20 patients from both families with idiopathic RLS but was not considered causative. The clinical phenotype did not differ between RLS patients with and without a Parkin mutation. Inheritance of RLS was consistent with autosomal dominant transmission, and linkage analysis excluded all three known loci for RLS.


Crystalline ribosomes are present in brains from senile humans.
Paracrystalline inclusions known as Hirano bodies characteristically appear in the hippocampal region of the brains of humans exhibiting senile and presenile dementias as well as several other neurodegenerative diseases. We present evidence that the currently accepted model for those structures based on alternating filament sheets is not correct, but that Hirano bodies are stacked sheets of membrane-bound ribosomal particles derived from partially degraded rough endoplasmic reticulum or Nissl substance. Using fluorescence staining with acridine orange and ethidium bromide, were have shown that the bodies contain RNA. Spatial filtering of electron micrographs by Fourier techniques shows that the individual particles that make up the arrays have a characteristic shape previously reported for the large subunit of eukaryotic ribosomes. The storage of these ribosomal particles in inclusion bodies may indicate a quiescent state of protein synthesis in the cells. This withdrawal of synthetic mechanisms in the hippocampus may have significant consequences in the loss of ability to consolidate short-term to long-term memory.


Rapid and sensitive identification of glycoprotein H genotypes in clinical human cytomegalovirus samples.
Human cytomegalovirus (HCMV) is a common pathogen that causes persistent infections in immune deficient patients and results in significant morbidity and mortality, particularly among transplant recipients and children. Different HCMV glycoprotein H (gH) genotypes may cause different diseases and affect the severity of these diseases. To develop a sensitive quantitative real-time PCR assay that could rapidly distinguish between two HCMV gH genotypes, primers were designed to target the conserved region of the gH gene. gH1 and gH2 probes were designed to target the two variable regions. Standard HCMV strains (AD169 and TOWNE) and 203 clinical urine samples from HCMV infected children were used for the present study. Based on the primer-probe set used to detect the target gH gene segment of HCMV, our quantitative real-time PCR assay specifically discriminated between HCMV gH1 and gH2 with a detection limit of approximately 10(2) viral copies/ml. Among the 203 clinical urine samples tested, 145 were gH1 positive, 56 were gH2 positive, and 2 were positive for both. Thus, we developed a gH gene-based real time-PCR method that could rapidly, stably, and specifically distinguish between two HCMV gH genotypes. We found HCMV gH1 to be common among children examined in Zhejiang, China.


Otosclerosis and endolymphatic hydrops.
It has been postulated that otosclerosis may produce vertigo by several mechanisms. One mechanism is by causing endolymphatic hydrops. We present six temporal bones in which otosclerosis and endolymphatic hydrops coexist. We consider that there is a spectrum-like interrelationship between these two entities. At one end of the spectrum the relationship is coincidental, while at the other end of the spectrum we consider the massive amount of active otosclerosis to be a causative factor in the development of the endolymphatic hydrops.


Lamotrigine therapy in infantile neuronal ceroid lipofuscinosis (INCL).
Since 1990, altogether 16 INCL patients received lamotrigine (LTG) because of intractable epilepsy. The response to LTG was favorable in 15/16 children. The severity of seizures decreased significantly in 15/16 patients, the frequency of seizures decreased in 14/16, and the effects were maintained. In addition, LTG had a beneficial effect on the well-being of 14/16 children. LTG failed to maintain it's efficacy in monotherapy. No severe side effects were found.


Adsorption mechanisms of chromate and phosphate on hydrotalcite: A combination of macroscopic and spectroscopic studies.
Hydrotalcite (HT) is a layered double hydroxide (LDH), which is considered as a potential adsorbent to remove anion contaminants. In this study, adsorption of chromate (CrO4) and phosphate (PO4) on HT was conducted at various pH and temperatures. Related adsorption mechanisms were determined via the isotherm, kinetic, and competitive adsorption studies as well as the Cr K-edge X-ray absorption fine-structure (XAFS) spectroscopy. The maximum adsorption capacities for CrO4 and PO4 on HT were 0.16 and 0.23 mmol g-1. Regarding adsorption kinetics, CrO4 and PO4 adsorption on HT could be well described by the second order model, and the rate coefficient of CrO4 and PO4 on HT decreased significantly with the increasing pH from 5 to 9. The adsorption kinetics for CrO4 and PO4 were divided into fast and slow stages with the boundary at 15 min. This biphasic adsorption behavior might be partially attributed to multiple reactive pathways including anion exchange and surface complexation. Fitting results of Cr K-edge EXAFS analysis showed a direct bonding between CrO4 and Al on HT surfaces. Such a surface complexation appeared to be the rate-limiting step for CrO4 adsorption on HT. By contrast, the diffusion through the hydrated interlayer space of HT was the major rate-limiting step for PO4. This study determined the adsorption behaviors of CrO4 and PO4 on HT, including the initial transfer process and the subsequent adsorption mechanisms. Such information could improve the strategy to use HT as the potential adsorbent for the remediation of anionic pollutants.


Double-stranded RNA virus in the human pathogenic fungus Blastomyces dermatitidis.
Double-stranded RNA viruses were detected in a strain of Blastomyces dermatitidis isolated from a patient in Uganda. The viral particles are spherical (mostly 44 to 50 nm in diameter) and consist of about 25% double-stranded RNA (5 kb) and 75% protein (90 kDa). The virus contains transcriptional RNA polymerase activity; it synthesized single-stranded RNA in vitro in a conservative manner. The newly synthesized single-stranded RNA was a full-length strand, and the rate of chain elongation was approximately 170 nucleotides per min. The virus-containing strain shows no morphological difference from virus-free strains in the mycelial phase. Although the association with the presence of the virus is unclear, the virus-infected strain converts to the yeast form at 37 degrees C, but the yeast cells fail to multiply at that temperature.


Selective laser trabeculoplasty retreatment after prior argon laser trabeculoplasty: 1-year results.
Argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) are treatments for open-angle glaucoma. Many patients have previously received ALT but could benefit from further treatment. The purpose of this study was to examine whether SLT provided clinical benefit for patients who had previously received complete argon treatment. This was a prospective, partially randomized, comparison study. The study compared the effect after 1 year of SLT in patients with open-angle glaucoma (primary, pigmentary, or pseudoexfoliation) who had previously received 360 degrees of ALT with the effect of laser treatment (ALT or SLT) given for the first time in patients with this condition. Ninety-six subjects were given 180 degrees of laser trabeculoplasty. When both eyes qualified for treatment, the first eye treated was included in the analysis. Twenty-seven subjects were treated with SLT after previously receiving 360 degrees of ALT therapy; the remainder were given their first laser treatment, 30 being randomly assigned by coin toss to receive SLT and 39 to receive ALT. The mean intraocular pressure (IOP) before treatment was 21.5 mm Hg (SLT after ALT), 22.9 mm Hg (SLT), and 22.0 mm Hg (ALT), with no statistical difference among the groups (p > 0.05). The mean IOP at 1 year was 16.7 mm Hg (SLT after ALT), 17.1 mm Hg (SLT), and 16.4 mm Hg (ALT). The IOP for all 3 groups was statistically significantly lower than at baseline (p < 0.001), but there were no differences among the groups in this respect (p > 0.05). At 1 year, the percentage IOP reductions from baseline were 23% (SLT), 19.3% (SLT after ALT), and 24% (ALT). There were no differences among the groups in the number of medications used before the laser, although there was a small but statistically significant decrease in the number of medications used before or after the laser treatment in both the SLT and the SLT after ALT group, but not the ALT group. SLT retreatment can produce a clinically useful decrease in IOP at 1 year, similar to that obtained by ALT, in patients who have had prior argon laser treatment. SLT may be a useful adjunctive therapy when 360 degrees of ALT has already been performed.


Bayesian assessment of the influence and interaction conditions in multipopulation tailoring clinical trials.
Multipopulation tailoring trials provide a trial design option that supports the realization of tailored therapeutics or personalized medicine. Several recent publications have focused on statistical and clinical considerations that arise in these trials that are designed to study the overall treatment effect in a population of interest as well as one or more prospectively defined subpopulations. Millen et al. (2012) introduced the influence and interaction conditions as part of a general framework to facilitate decision making in multipopulation trials. This article provides Bayesian methods for assessing the influence and interaction conditions. The methods introduced are illustrated using case studies based on clinical trials with biomarker-driven designs.


The relationship between purines, pyrimidines, nucleosides, and glutamine for fibroblast cell proliferation.
Previous studies indicate that glutamine is a critical requirement for cell proliferation in vitro. We recently showed that depletion of glutamine from the culture medium supporting growing cells significantly reduced the proportion of cells undergoing DNA synthesis. Similarly glutamine depletion significantly reduced the stimulatory response of quiescent cells to 10% serum. This study shows that the inhibitory effects of depletion of glutamine--in either of these two situations--can be overcome by the addition of adenine or adenosine. Adenine was the only nitrogen base and adenosine was the only nucleoside for which this effect was observed. Such effects could, however, also be achieved by addition of the purine metabolites hypoxantine and inosine. Furthermore, it was found that glutamine (or adenine/adenosine) is only required during a limited interval coinciding with the late part of the G1-phase and the beginning of S-phase. These data suggest the possibility that glutamine exerts its main regulatory effects on cell proliferation by acting as a precursor for adenine and adenosine.


Evolutionary divergence of the Citrobacter freundii tryptophan operon regulatory region: comparison with other enteric bacteria.
The regulatory region of the trp operon of Citrobacter freundii was sequenced and compared with the corresponding regions of other enteric bacteria. Significant differences were noted in the promoter region. These differences are presumably responsible for the weak expression of the cloned trp operon in Escherichia coli. The presumed operator region, although nonfunctional in E. coli, has dyad symmetry, but the sequence of the symmetrical region differs appreciably from those of operators that can be regulated by the E. coli trp repressor. The sequence of the trp leader region of C. freundii resembles that of other enteric bacteria, suggesting that the C. freundii operon is also regulated by attenuation. Comparison of the sequence of the initial portion of trpE with the homologous regions of E. coli and Salmonella typhimurium indicates that the three organisms probably are evolutionary equidistant.