Electrophoretic variants of enzymes in isolates of Plasmodium falciparum, P. malariae and P. vivax from Thailand.
A new electrophoretic variant of glucose phosphate isomerase (GPI), which we now denote GPI-3, has been found in isolates of Plasmodium falciparum from 6 patients, all of whom acquired the infection in the same region (in or near Prachinburi province) of Thailand. In other regions, from which 453 isolates have been tested, only GPI-1 and/or GPI-2 have been found. Two isolates of P. malariae from patients at Kanchanaburi showed a band of GPI activity on cellulose acetate gels at a cathodal position quite distinct from that of any previously known GPI variants in other human malaria parasites. Thirty-nine isolates of P. vivax from 3 regions of Thailand have been examined for variants of GPI and lactate dehydrogenase (LDH). Three forms of GPI were found, corresponding approximately in band positions to GPI-1, 2 and 3 of P. falciparum. The position of the band of LDH activity in P. vivax was the same in all the isolates examined, and different from that of LDH-1 in P. falciparum.


[Bed capacity management in times of the COVID-19 pandemic : A simulation-based prognosis of normal and intensive care beds using the descriptive data of the University Hospital Augsburg].
Following the regional outbreak in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread all over the world, presenting the healthcare systems with huge challenges worldwide. In Germany the coronavirus diseases 2019 (COVID-19) pandemic has resulted in a slowly growing demand for health care with a sudden occurrence of regional hotspots. This leads to an unpredictable situation for many hospitals, leaving the question of how many bed resources are needed to cope with the surge of COVID-19 patients. In this study we created a simulation-based prognostic tool that provides the management of the University Hospital of Augsburg and the civil protection services with the necessary information to plan and guide the disaster response to the ongoing pandemic. Especially the number of beds needed on isolation wards and intensive care units (ICU) are the biggest concerns. The focus should lie not only on the confirmed cases as the patients with suspected COVID-19 are in need of the same resources. For the input we used the latest information provided by governmental institutions about the spreading of the disease, with a special focus on the growth rate of the cumulative number of cases. Due to the dynamics of the current situation, these data can be highly variable. To minimize the influence of this variance, we designed distribution functions for the parameters growth rate, length of stay in hospital and the proportion of infected people who need to be hospitalized in our area of responsibility. Using this input, we started a Monte Carlo simulation with 10,000 runs to predict the range of the number of hospital beds needed within the coming days and compared it with the available resources. Since 2 February 2020 a total of 306 patients were treated with suspected or confirmed COVID-19 at this university hospital. Of these 84 needed treatment on the ICU. With the help of several simulation-based forecasts, the required ICU and normal bed capacity at Augsburg University Hospital and the Augsburg ambulance service in the period from 28 March 2020 to 8 June 2020 could be predicted with a high degree of reliability. Simulations that were run before the impact of the restrictions in daily life showed that we would have run out of ICU bed capacity within approximately 1 month. Our simulation-based prognosis of the health care capacities needed helps the management of the hospital and the civil protection service to make reasonable decisions and adapt the disaster response to the realistic needs. At the same time the forecasts create the possibility to plan the strategic response days and weeks in advance. The tool presented in this study is, as far as we know, the only one accounting not only for confirmed COVID-19 cases but also for suspected COVID-19 patients. Additionally, the few input parameters used are easy to access and can be easily adapted to other healthcare systems.


Mucosal healing of Crohn's disease in a patient with concurrent systemic lupus erythematosus using infliximab.
We describe a patient with Crohn's disease (CD) concurrent with systemic lupus erythematosus (SLE). Continuous prednisolone and cyclosporine treatment resulted in no recurrent symptoms. However, diarrhea, vomiting, and fever occurred for approximately 3 months. A colonoscopy was then performed, which showed a discontinuous cobblestone appearance and longitudinal ulcers extending from the sigmoid colon to the descending colon and distal ileum. A biopsy revealed a noncaseating granulomatous lesion in the colonic mucosa. These findings led to a diagnosis of CD concurrent with SLE. We first attempted treatment with a full elemental diet, mesalazine, and azathioprine, in that order. However, as there was no improvement in inflammation, we started infliximab, a tumor necrosis factor-alpha inhibitor. Transanal double-balloon enteroscopy performed 4 months after starting infliximab showed mucosal healing, suggesting that infliximab was effective. There are few reports of treating patients with CD concurrent with SLE using a tumor necrosis factor-alpha inhibitor. We report our experience with a patient who had mucosal healing with infliximab and review the literature.


Drivers of phenology shifts and their effect on productivity in northern grassland of China during 1984-2017-evidence from long-term observational data.
Plant phenology under changing climate is a critical factor controlling terrestrial vegetation productivity. However, large uncertainties exist due to different data sources and phenological parameter extraction methods. In this study, we took advantage of a suite of long-term field observational data in northern grassland of China to investigate the drivers of phenological shifts and their effect on the maximum aboveground net primary productivity (ANPPmax) across four representative grassland types during 1984-2017. Results showed that drivers of phenological events (i.e., start (SOS), end (EOS), and length (GSL) of the growing season) with warming influence dramatically differed among grassland types, indicating that the synergistic effect of temperature and precipitation should be highlighted. For temperate desert steppe and alpine meadow, GSL of dominant species was both significantly lengthened with temperature rising with averaged 0.94 days year-1 (P < 0.001) and 1.15 days year-1 (P < 0.001), respectively, while for typical temperate grassland, GSL was considerably shortened by an average of 0.58 days year-1 (P < 0.01) as a result of water deficit caused by sharp warming and precipitation decreasing in summer and autumn. For most grassland types in our study, both SOS and GSL were significantly correlated with ANPPmax under different precipitation gradients with SOS advanced and GSL extended leading to higher ANPPmax. Only the typical temperate grassland presents a relatively poor correlation between phenological events and productivity. Furthermore, compared with GSL, ANPPmax was more sensitive to the advancement of SOS for every 1-day phenological change. However, the effect of EOS on ANPPmax across the four grassland types was much weaker and unstable. There were spatial response differences between ANPPmax and phenological transition events, with the temperate meadow grassland tending to be more sensitive compared with three other grassland types.


The cognitive architecture of processes responsible to assess similarity and clarity in a comparison task.
When asked to compare two stimuli, participants are on average faster to respond Same than Different, an effect coined the fast-same. The dual-process theory argues that information about similarity is processed in priority over any other type of information, causing the fast-same effect. We tested this serial architecture of cognitive processes using a double factorial paradigm, suitable for a Systems Factorial Technology (SFT) analysis. Twenty participants completed a task in which they compared two letters, which were varied on two dimensions: the similarity and the clarity of the letters. Their task was to indicate if the second letter was the Same as the second letter (ranging from identical and clear to similar and slightly blurry) or if it was Different (if the stimuli were either dissimilar or very blurry). The SFT results show that most participants processed the information in serial, but in a mixed order. In other words, for some trials, participants processed similarity first, and for some other trials, they processed clarity first. This implies that participant indeed processed information in serial in the comparison task, but that it does not cause the fast-same effect.


Life-history traits and effective population size in species with overlapping generations revisited: the importance of adult mortality.
The relationship between life-history traits and the key eco-evolutionary parameters effective population size (Ne) and Ne/N is revisited for iteroparous species with overlapping generations, with a focus on the annual rate of adult mortality (d). Analytical methods based on populations with arbitrarily long adult lifespans are used to evaluate the influence of d on Ne, Ne/N and the factors that determine these parameters: adult abundance (N), generation length (T), age at maturity (α), the ratio of variance to mean reproductive success in one season by individuals of the same age (φ) and lifetime variance in reproductive success of individuals in a cohort (Vk•). Although the resulting estimators of N, T and Vk• are upwardly biased for species with short adult lifespans, the estimate of Ne/N is largely unbiased because biases in T are compensated for by biases in Vk• and N. For the first time, the contrasting effects of T and Vk• on Ne and Ne/N are jointly considered with respect to d and φ. A simple function of d and α based on the assumption of constant vital rates is shown to be a robust predictor (R(2)=0.78) of Ne/N in an empirical data set of life tables for 63 animal and plant species with diverse life histories. Results presented here should provide important context for interpreting the surge of genetically based estimates of Ne that has been fueled by the genomics revolution.


Sub-lethal plant defences: the paradox remains.
Lodgepole pine (Pinus contorta) trees of two different seed origins, one a poor quality host (Alaskan lodgepole pine), the other a good quality host (south coastal lodgepole pine), were infested with known numbers of eggs of the pine beauty moth, Panolis flammea. Each tree had paired sleeves, one allowing access by invertebrate predators, the other denying this access. When the sleeves were removed, the numbers of larvae surviving, their weights and developmental stages were assessed. Larvae reared on south coastal lodgepole pine (SLP) in the absence of predators were significantly heavier and had significantly better survival rates than larvae reared in comparable conditions on Alaskan lodgepole pine (ALP). However, in the open sleeves, although the larvae reared on SLP were significantly heavier than those on ALP, survival was significantly greater on ALP. Thus predation was greater on the faster developing larvae on the better quality host. These results indicate that slow growth by a herbivore does not necessarily result in greater vulnerability to predators.


Analgesia induced by exposure to a novel environment in rats: effect of concurrent and post-training stressful stimulation.
Exposure of rats for 2 min to a new environment (a 50 X 25 X 25-cm box) induced a mild analgesia measured by the tail-flick method. Additional stressful stimuli (0.5 mA, 1.5-s footshocks, light flashes, or tones) presented during the 2-min exposure did not alter the analgesia. However, the postexposure presentation of light flashes or tones, for either 10 s or 2 min, while the animals were alone in a waiting cage, prevented the analgesic response. Similarly, placing the subjects with their conspecifics in the home cage for 2 min after the exposure prevented the analgesic response. The data suggest that the analgesia may represent a physiological correlate of novelty and that the response can be impaired by post-training treatments.


Effect of Promoting High-Quality Staff Interactions on Fall Prevention in Nursing Homes: A Cluster-Randomized Trial.
New approaches are needed to enhance implementation of complex interventions for geriatric syndromes such as falls. To test whether a complexity science-based staff training intervention (CONNECT) promoting high-quality staff interactions improves the impact of an evidence-based falls quality improvement program (FALLS). Cluster-randomized trial in 24 nursing homes receiving either CONNECT followed by FALLS (intervention), or FALLS alone (control). Nursing home staff in all positions were asked to complete surveys at baseline, 3, 6, and 9 months. Medical records of residents with at least 1 fall in the 6-month pre- and postintervention windows (n = 1794) were abstracted for fall risk reduction measures, falls, and injurious falls. CONNECT taught staff to improve their connections with coworkers, increase information flow, and use cognitive diversity in problem solving. Intervention components included 2 classroom sessions, relationship mapping, and self-monitoring. FALLS provided instruction in the Agency for Healthcare Research and Quality's Falls Management Program. Primary outcomes were (1) mean number of fall risk reduction activities documented within 30 days of falls and (2) median fall rates among residents with at least 1 fall during the study period. In addition, validated scales measured staff communication quality, frequency, timeliness, and safety climate. Surveys were completed by 1545 staff members, representing 734 (37%) and 811 (44%) of eligible staff in intervention and control facilities, respectively; 511 (33%) respondents were hands-on care workers. Neither the CONNECT nor the FALLS-only facilities improved the mean count of fall risk reduction activities following FALLS (3.3 [1.6] vs 3.2 [1.5] of 10); furthermore, adjusted median recurrent fall rates did not differ between the groups (4.06 [interquartile range {IQR}, 2.03-8.11] vs 4.06 [IQR, 2.04-8.11] falls/resident/y). A modest improvement in staff communication measures was observed overall (mean, 0.03 [SE, 0.01] points on a 5-point scale; P = .03) and for communication timeliness (mean, 0.8 [SE, 0.03] points on a 5-point scale; P = .02). There was wide variation across facilities in intervention penetration. An intervention targeting gaps in staff communication and coordination did not improve the impact of a falls quality improvement program. New approaches to implementing evidence-based care for complex conditions in the nursing home are urgently needed. clinicaltrials.gov Identifier: NCT00636675.


[The relation between cord compression rate and the outcome of surgical treatment].
To study the relation of compressive spinal cord changes in morphology with postoperative results. 114 cases of operative patients were divided in to three groups: ossification of posterior longitudinal ligament (OPLL), cervical spondylotic myelopathy (CSM), and cervical intervertebral disc herination. The spinal cord plane and to the compressive ratio in the most heavily pressed position were measured according to the JOA record. The compressive ratio and the plane were not corelated with clinical history. The spinal cord plane was positively corelated with the recovery rate. The preoperative spinal cord plane in OPLL and CSM is mostly corelated with the recovery rate.


Development of Quality Indicators for Cardiac Rehabilitation in Australia: A Modified Delphi Method and Pilot Test.
International guidelines recommend cardiac rehabilitation (CR) for secondary prevention of cardiovascular disease, however, it is underutilised and the quality of content and delivery varies widely. Quality indicators (QIs) for CR are used internationally to measure clinical practice performance, but are lacking in the Australian context. This study reports the development of QIs for minimum dataset (MDS) for CR and the results of a pilot test for feasibility and applicability in clinical practice in Australia. A modified Delphi method was used to develop initial QIs which involved a consensus approach through a series of face-to-face and teleconference meetings of an expert multidisciplinary panel (n=8), supplemented by an environmental scan of the literature and a multi-site pilot test. Eight (8) QIs were proposed and sent to CR clinicians (n=250) electronically to rate importance, current data collection status, and feasibility of future collection. The top six of these QIs were selected with an additional two key performance indicators from the New South Wales (NSW) Ministry of Health and two QIs from international registers for a draft MDS. The pilot test in 16 sites (938 patient cases) demonstrated median performance of 93% (IQR 47.1-100%). All 10 QIs were retained and one further QI related to diabetes was added for a final draft MDS. The MDS of 11 QIs for CR provides an important foundation for collection of data to promote the quality of CR nationally and the opportunity to participate in international benchmarking.


Circulation of 2 Barmah Forest Virus Lineages in Military Training Areas, Australia.
During 2017-2018, Barmah Forest virus was recovered from mosquitoes trapped in military training areas in Australia and from a soldier infected at 1 of these areas. Phylogenies of the nucleotide sequences of the envelope glycoprotein gene E2 and the 3' untranslated region suggest that 2 lineages are circulating in eastern Australia.


Inoculation with abscisic acid (ABA)-catabolizing bacteria can improve phytoextraction of heavy metal in contaminated soil.
Promotion of plant capacity for accumulation of heavy metals (HMs) is one of the key strategies in enhancing phytoremediation in contaminated soils. Here we report that, Rhodococcus qingshengii, an abscisic acid (ABA)-catabolizing bacteria, clearly boosts levels of Cd, Zn, and Ni in wild-type Arabidopsis by 47, 24, and 30%, respectively, but no increase in Cu was noted, when compared with non-inoculated Arabidopsis plants in contaminated growth substrate. Furthermore, when compared with wild-type plants, R.qingshengii-induced increases in Cd, Zn, and Ni concentrations were more pronounced in abi1/hab1/abi2 (ABA-sensitive mutant) strains of Arabidopsis, whereas little effect was observed in snrk2.2/2.3 (ABA insensitive mutant). This demonstrates that metabolizing ABA might be indispensable for R. qingshengii to improve metal accumulation in plants. Bacterial inoculation significantly elevated the expression of Cd, Zn, and Ni-related transporters; whereas the transcript levels of Cu transporters remained unchanged. This result may be a reasonable explanation for why the uptake of Cd, Zn, and Ni in plants was stimulated by bacterial inoculation, while no effect was observed on Cu levels. From our results, we clearly demonstrate that R. qingshengii can increase the accumulation of Cd, Zn, and Ni in plants via an ABA-mediated HM transporters-associated mechanism. Metabolizing ABA in the plants by ABA-catabolizing bacterial inoculation might be an alternative strategy to improve phytoremediation efficiency in HMs contaminated soil.


Severe polymicrobial and fungal periprosthetic osteomyelitis persisting after hip disarticulations treated with caspofungin in risk patients: a case series.
Periprosthetic fungal infections are considered rare and opportunistic infections. Treatment is difficult, and established standards do not yet exist. The choice of the appropriate antifungal drug might affect the patient outcome. All the three cases presented showed polybacterial recurrent infection of the revision hip arthroplasty. All patients were of younger age, had multiple revisions of the endoprosthesis, each had a large partial femoral replacement greater than 40% of the femoral length, gentamycin-loaded cement, and a long anchoring distance of the used intramedullary stem. Due to the severe life-threatening infection with deep osteomyelitis, an amputation had to be performed. However, despite surgical intervention, the fungal dominated infection persisted. Finally, only the use of caspofungin allowed permanent infection control. The polybacterial infection is driven by the symbiosis between fungi and bacteria. Therefore, eradication of the fungus is required to achieve elimination of the bacteria. Antimycotics of the echinocandin-class, such as caspofungin, may be considered as initial treatment.


Right-to-left shunt in CADASIL patients: prevalence and correlation with clinical and MRI findings.
A high prevalence of right-to-left shunt (RLS) was described in a family of patients with CADASIL, a rare cerebral arteriopathy attributable to Notch3 gene mutations. The aim of this study was to determine the prevalence of RLS in patients with CADASIL and possible relation to clinical phenotype and cerebral MRI lesion load. Twenty-three CADASIL patients underwent Transcranial Doppler with gaseous contrast to asses RLS. Correlations between RLS, clinical features, and MRI lesion volume (LV) were determined. Large RLS was diagnosed in 47% of patients. No significant clinical or MRI differences were found between patients with and without RLS. We found a high prevalence of RLS in our group of CADASIL patients. This may not be a coincidence, but can be rather related to the role of the Notch receptor family in the development of cardiovascular system.


Payor mix of trauma patients at a rural-metropolitan regional trauma center: a three-year experience.
The development of a statewide trauma system will depend on designation of community hospitals as trauma centers. The financial impact of such designation will be a prime concern. The payor mix of trauma patients will be one of the deciding factors as to whether hospitals will agree to accept designation. A three-year review of payor class on discharge for 2,605 trauma and 55,041 nontrauma admissions to a nonuniversity teaching hospital is presented. Sixty-four percent of all trauma admissions had third-party payor insurance coverage, compared with 72% of all nontrauma admissions (P less than .00001). Twenty-seven percent of trauma admissions were for penetrating injury. Sixty-eight percent of patients admitted for blunt trauma had third-party coverage, while 50% of those admitted for penetrating trauma had third-party coverage. Total commercial insurance coverage was higher for trauma patients than for nontrauma admissions. The payor class mix for trauma patients presented may be representative of similar institutions in a similar geographic setting and may offer assistance to hospitals considering the financial impact of trauma center designation.


The roles of collagen in chronic kidney disease and vascular calcification.
The extracellular matrix component collagen is widely expressed in human tissues and participates in various cellular biological processes. The collagen amount generally remains stable due to intricate regulatory networks, but abnormalities can lead to several diseases. During the development of renal fibrosis and vascular calcification, the expression of collagen is significantly increased, which promotes phenotypic changes in intrinsic renal cells and vascular smooth muscle cells, thereby exacerbating disease progression. Reversing the overexpression of collagen substantially prevents or slows renal fibrosis and vascular calcification in a wide range of animal models, suggesting a novel target for treating patients with these diseases. Stem cell therapy seems to be an effective strategy to alleviate these two conditions. However, recent findings indicate that the natural pore structure of collagen fibers is sufficient to induce the inappropriate differentiation of stem cells and thereby exacerbate renal fibrosis and vascular calcification. A comprehensive understanding of the role of collagen in these diseases and its effect on stem cell biology will assist in improving the unmet requirements for treating patients with kidney disease.


Different effect of diltiazem and nifedipine on some central actions of ethanol in the rat.
The effect of two Ca2+ channel inhibitors (CCIs) on ethanol-induced hypothermia and hypnosis, on tolerance formation to both effects, and on audiogenic convulsions during ethanol withdrawal was studied in rats. Nifedipine, 2 and 5 mg/kg IP, significantly augmented the hypnotic action of ethanol without affecting hypothermia. Diltiazem failed to influence either effect of the toxin. Rectal temperature did not change in ethanol-naive rats after acute injection of diltiazem or nifedipine. Both drugs dose-dependently suppressed the development of tolerance to the hypothermic effect of ethanol without affecting the tolerance to the hypnotic action. Only nifedipine markedly suppressed the audiogenic seizure response in ethanol withdrawn animals. These data suggest that Ca2+ channels play a role in both acute and chronic effects of ethanol while pointing to certain differences in behavioral effects of various CCIs.


Cross-cover of oral and maxillofacial surgery out-of-hours: an audit of a new adult treatment clinic.
We present our experience of launching the adult treatment clinic - a daytime clinic for semiurgent referrals to oral and maxillofacial surgery (OMFS). This has proved to be an effective way in which cross-covering junior doctors could refer patients for a safe and efficient review in a supervised environment.


Induction of diapause in a migratory seed bug, Neacoryphus bicrucis (Say) (Heteroptera: Lygaeidae).
Neacoryphus bicrucis hibernates in the adult stage and exhibits a facultative reproductive diapause. Constant photoperiods of the durations encountered in the field do not evoke the diapause response but Shortening of the photoperiods does, providing the decrease in daylength is of a certain length and occurs within a certain photoperiodic interval. The sensitive stages are larval instars II to V. The percentage of diapausing bugs increases as temperature is lowered.It is suggested that the response to daylength shortening in N. bicrucis is an adaptation to ensure seasonal synchronization in a highly migratory species where successive generations may breed at different latitudes.


In-situ Observation of Cross-Sectional Microstructural Changes and Stress Distributions in Fracturing TiN Thin Film during Nanoindentation.
Load-displacement curves measured during indentation experiments on thin films depend on non-homogeneous intrinsic film microstructure and residual stress gradients as well as on their changes during indenter penetration into the material. To date, microstructural changes and local stress concentrations resulting in plastic deformation and fracture were quantified exclusively using numerical models which suffer from poor knowledge of size dependent material properties and the unknown intrinsic gradients. Here, we report the first in-situ characterization of microstructural changes and multi-axial stress distributions in a wedge-indented 9 μm thick nanocrystalline TiN film volume performed using synchrotron cross-sectional X-ray nanodiffraction. During the indentation, needle-like TiN crystallites are tilted up to 15 degrees away from the indenter axis in the imprint area and strongly anisotropic diffraction peak broadening indicates strain variation within the X-ray nanoprobe caused by gradients of giant compressive stresses. The morphology of the multiaxial stress distributions with local concentrations up to -16.5 GPa correlate well with the observed fracture modes. The crack growth is influenced decisively by the film microstructure, especially by the micro- and nano-scopic interfaces. This novel experimental approach offers the capability to interpret indentation response and indenter imprint morphology of small graded nanostructured features.


Monitoring bacterial composition and assemblage in the Gulf of Corcovado, southern Chile: Bacteria associated with harmful algae.
Harmful Algal Blooms (HABs) have caused damage to the marine environment in Isla San Pedro in the Gulf of Corcovado, Chile. While rising water temperature and artificial eutrophication are the most discussed topics as a cause, marine bacteria is a recent attractive parameter as an algal bloom driver. This study monitored algal and bacterial compositions in the water of Isla San Pedro for one year using microscopy and 16S rRNA metabarcoding analysis, along with physicochemical parameters. The collected data were analyzed with various statistical tools to understand how the particle-associated bacteria (PA) and the free-living (FL) bacteria were possibly involved in algal blooms. Both FL and PA fractions maintained a stable bacterial composition: the FL fraction was dominated by Proteobacteria (α-Proteobacteria and γ-Proteobacteria), and Cyanobacteria dominated the PA fraction. The two fractions contained equivalent bacterial taxonomic richness (c.a. 8,000 Operational Taxonomic Units) and shared more than 50% of OTU; however, roughly 20% was exclusive to each fraction. The four most abundant algal genera in the Isla San Pedro water were Thalassiosira, Skeletonema, Chaetoceros, and Pseudo-nitzchia. Statistical analysis identified that the bacterial species Polycyclovorans algicola was correlated with Pseudo-nitzschia spp., and our monitoring data recorded a sudden increase of particle-associated Polycyclovorans algicola shortly after the increase of Pseudo-nitzschia, suggesting that P. algicola may have regression effect on Pseudo-nitzschia spp. The study also investigated the physicochemical parameter effect on algal-bacterial interactions. Oxygen concentration and chlorophyll-a showed a strong correlation with both FL and PA bacteria despite their assemblage differences, suggesting that the two groups had different mechanisms for interacting with algal species.


Duodenal bile acids in diagnosis of congenital biliary atresia.
This diagnostic study was useful in distinguishing between complete and partial biliary obstruction in a small number of cases. It has been used widely in Japan and is published here to bring it to the attention of other investigators.


Activity of meropenem with and without ciprofloxacin and colistin against Pseudomonas aeruginosa and Acinetobacter baumannii.
Time-kill synergy studies showed that at 24 h, subinhibitory meropenem and ciprofloxacin concentrations of 0.06 to 128 and 0.03 to 32 microg/ml, respectively, showed synergy against 34/51 Pseudomonas aeruginosa strains; subinhibitory concentrations of meropenem (0.06 to 8 microg/ml) and colistin (0.12 to 1 microg/ml) showed synergy against 13 isolates. Subinhibitory meropenem and ciprofloxacin concentrations of 0.25 to 2 and 0.12 to 16 microg/ml, respectively, showed synergy against 18/52 Acinetobacter baumannii strains at 24 h. Subinhibitory meropenem and colistin concentrations of 0.03 to 64 and 0.06 to 8 microg/ml, respectively, showed synergy against 49 strains at 24 h.


Identification of patients with non-d, non-C irritable bowel syndrome and treatment with renzapride: an exploratory, multicenter, randomized, double-blind, placebo-controlled clinical trial.
This was an exploratory study of renzapride in 168 male and female patients with non-D, non-C irritable bowel syndrome (IBS). Patients were randomized to placebo or renzapride (1, 2, or 4 mg/day) for 8 weeks. The primary efficacy variable was patient-reported satisfactory relief of IBS symptoms. Secondary variables included relief of abdominal pain/discomfort. The proportion of patients reporting satisfactory relief of their IBS symptoms for at least 50% of the time did not differ significantly from those on placebo. However, post hoc analysis in women showed differences in responder rate on renzapride versus placebo of 18.2% (95% CI -5% to 42%; P = 0.066) during weeks 1-4 and 6% (95% CI -21% to 33%; P = 0.339) during weeks 5-8. Renzapride was well tolerated and most adverse events were mild to moderate in intensity. Further studies are warranted to determine whether renzapride is beneficial in this patient population.


Lactate and pyruvate metabolism in isolated renal tubules of normal dogs.
The kinetics of lactate and pyruvate (1 and 5 mM in each case) metabolism was studied in isolated dog renal tubules. Utilization of these two substrates and the production of glucose, pyruvate, or lactate, and alanine were determined. The rates of lactate and pyruvate utilization and of glucose production were constant during 60 min of incubation. Glucose production from pyruvate was less than that from lactate. Addition of albumin to the incubation medium greatly inhibited lactate and pyruvate utilization at both substrate concentrations. It stimulated, however, glucose production from 1 mM, but not 5 mM, lactate or pyruvate. These effects were found to be due to the presence of fatty acids in the albumin solution used. In the absence of fatty acids, glucose production represented 35 to 40% of lactate uptake, but represented less than 20% of pyruvate uptake. Fatty acids markedly enhanced the percentage of transformation of lactate and pyruvate into glucose, and that of pyruvate into lactate. Alanine represented 20% or less of lactate and pyruvate uptake. These results suggest that fatty acids have a regulatory influence on lactate and pyruvate dog kidney metabolism.


The importance of work organization on workload and musculoskeletal health--Grocery store work as a model.
We have evaluated the consequences of work organization on musculoskeletal health. Using a postal questionnaire, answered by 1600 female grocery store workers, their main work tasks were identified and four work groups were defined (cashier, picking, and delicatessen work, and a mixed group, who performed a mix of these tasks). The crude odds ratios (ORs) for neck/shoulder complaints were 1.5 (95% CI 1.0-2.2), 1.1 (0.7-1.5) and 1.6 (1.1-2.3), respectively, compared to mixed work. Adjusting for individual and psychosocial factors had no effect on these ORs. For elbows/hands, no significant differences were found. Technical measurements of the workload showed large differences between the work groups. Picking work was the most strenuous, while cashier work showed low loads. Quantitative measures of variation revealed for mixed work high between minutes variation and the highest between/within minutes variation. Combining work tasks with different physical exposure levels increases the variation and may reduce the risk of musculoskeletal complaints.


Polythiophene-coated Fe3O4 superparamagnetic nanocomposite: synthesis and application as a new sorbent for solid-phase extraction.
In the present work, a novel type of superparamagnetic nanosorbent, polythiophene-coated Fe3O4 nanoparticles (Fe3O4@PTh NPs), have been successfully synthesized. The synthesized NPs were characterized by scanning electron microscopy (SEM), Fourier transform-infrared (FT-IR) spectroscopy, and thermal gravimetric analysis (TGA). The synthesized Fe3O4@PTh NPs were applied as an efficient sorbent for extraction and preconcentration of several typical plasticizer compounds (di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP), and dioctyl adipate (DOA)) from environmental water samples. Separation of Fe3O4@PTh NPs from the aqueous solution was simply achieved by applying external magnetic field. Separation and determination of the extracted plasticizers was performed by gas chromatography-flame ionization detection (GC-FID). Several variables affecting the extraction efficiency of the analytes i.e., amount of NPs sorbent, salt concentration, extraction time, and desorption conditions were investigated and optimized. The best working conditions were as follows: amount of sorbent, 100 mg; NaCl concentration, 30% (w/v); sample volume, 45 mL; extraction time, 10 min; and 100 μL of ethyl acetate for desorption of the analytes within 2 min. Under optimized conditions, preconcentration factors for DBP, DEHP, and DOA were obtained as 86, 194, and 213, respectively. The calibration curves were linear (R(2)>0.998) in the concentration range of 0.4-100 μg L(-1) for both DEHP and DOA and 0.7-100 μg L(-1) for DBP. The limits of detection (LODs) were obtained in the range of 0.2-0.4 μg L(-1). The intra-day relative standard deviations (RSDs%) based on four replicates were obtained in the range of 4.0-12.3%. The proposed procedure was applied to analysis of water samples including river water, bottled mineral water, and boiling water exposed to polyethylene container (after cooling) and recoveries between 85 and 99% and RSDs lower than 12.8% were obtained.


Mammalian-heart adenylate deaminase: cross-species immunoanalysis of tissue distribution with a cardiac-directed antibody.
A sheep antiserum against purified rabbit-heart adenylate deaminase (EC 184.108.40.206) (AMPD) was developed and validated as an immunologic probe to assess the cross-species tissue distribution of the mammalian cardiac AMPD isoform. The antiserum and the antibodies purified therefrom recognized both native and denatured rabbit-heart AMPD in immunoprecipitation and immunoblot experiments, respectively, and antibody binding did not affect native enzyme activity. The immunoprecipitation experiments further demonstrated a high antiserum titer. Immunoblot analysis of either crude rabbit-heart extracts or purified rabbit-heart AMPD revealed a major immunoreactive band with the molecular mass (approximately 81 kDa) of the soluble rabbit-heart AMPD subunit. AMPD in heart extracts from mammalian species other than rabbit (including human) was equally immunoreactive with this antiserum by quantitative immunoblot criteria. Although generally held to be in the same isoform class as heart AMPD, erythrocyte AMPD was not immunoreactive either within or across species. Nor was AMPD from most other tissues [e.g., white (gastrocnemius) muscle, lung, kidney] immunoreactive with the cardiac-directed antibody. Limited immunoreactivity was evidenced by mammalian liver, red (soleus) muscle, and brain extracts across species, indicating the presence of a minor cardiac(-like) AMPD isoform in these tissues. The results of this study characterize the tissue distribution of the cardiac AMPD isoform using a molecular approach with the first polyclonal antibodies prepared against homogeneous cardiac AMPD. This immunologic probe should prove useful at the tissue level for AMPD immunohistochemistry.


Implementing Routine HIV Screening in Hospitals: An Effective Practice to Expand HIV Testing - Xishuangbanna Prefecture, Yunnan Province, China, 2019-2020.
Research evidence is insufficient to suggest whether routine human immunodeficiency virus (HIV) screening in healthcare settings is effective in promoting greater awareness of HIV-positive status. This study found that, following the implementation of routine HIV screening in hospitals in Xishuangbanna Prefecture, Yunnan Province, there was a significant increase in the number of HIV screenings, positive results, and the positive rate of HIV screening in primary-level hospitals. Routine hospital-based HIV screening is effective in identifying HIV infections in areas with concentrated epidemics.


Domain-wide displacement of histones by activated heat shock factor occurs independently of Swi/Snf and is not correlated with RNA polymerase II density.
We show that histone-DNA interactions are disrupted across entire yeast heat shock genes upon their transcriptional activation. At HSP82, nucleosomal disassembly spans a domain of approximately 3 kb, beginning upstream of the promoter and extending through the transcribed region. A kinetic analysis reveals that histone H4 loses contact with DNA within 45 s of thermal upshift. Nucleosomal reassembly, prompted by temperature downshift, is also rapid, detectable within 60 s. Prior to their eviction, promoter-associated histones are transiently hyperacetylated, while those in the coding region are not. An upstream activation sequence mutation that weakens the binding of heat shock factor obviates domain-wide remodeling, while deletion of the TATA box that nearly abolishes transcription is permissive to 5'-end remodeling. The Swi/Snf complex is rapidly recruited to HSP82 upon heat shock. Nonetheless, domain-wide remodeling occurs efficiently in Swi/Snf mutants despite a sixfold reduction in transcription; it is also seen in gcn5Delta, set1Delta, and paf1Delta mutants. Contrary to current models, we demonstrate that a high density of RNA polymerase (Pol) is insufficient to elicit histone displacement. This finding suggests that histone eviction is modulated by factors that are not linked to elongating Pol II. It further suggests that histone depletion plays a causal role in mediating vigorous transcription in vivo and is not merely a consequence of it.


Water exchange on a geological timescale - examples from two coastal sites in the Baltic Sea.
The water turnover of two coastal areas, Forsmark and Laxemar-Simpevarp, has been modeled for 13 selected years between 6500 BC and 9000 AD by utilizing information about past, present, and future bathymetry. The Forsmark area can be described as an open-ended funnel, and is analyzed with a 3D-model (MIKE 3-FM); the Laxemar area is partitioned into clusters of sub-basins treated with a discrete coupled basin model (CouBa). In all simulations, the main variation factor is the land uplift. The 3D-model domain is successively modified. For the CouBa approach the successive basin configurations are objectively deduced based on the 3D domain modifications. The average age (AvA) of the resident water relative to the open coast is generally lower for the Forsmark area. A typical progression is that the AvA values increase until a sub-basin ceases to be connected to the coastal zone. This disconnection is often preceded by a lowered AvA.


[On the synthesis of the cerebrally active compound tinofedrine (author's transl)].
The synthesis of tinofedrine (I), (+)-(R)-alpha-((S)-1-[3,3-di-3-thienylallyl)amino]benzylalcohol, a new cerebrally active drug, and the verification of its structure by spectrometric methods are reported.


Suppression of MALAT1 alleviates neurocyte apoptosis and reactive oxygen species production through the miR-499-5p/SOX6 axis in subarachnoid hemorrhage.
Subarachnoid hemorrhage (SAH), a common devastating cerebrovascular accident, is a great threat to human health and life. Exploration of the potential therapeutic target of SAH is urgently needed. Previous studies showed that long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes cell apoptosis in various diseases, while its role in SAH remains unclear. In our study, we established a mouse model of SAH and used the oxyhemoglobin (OxyHb) to induce neuronal injury in vitro. Interestingly, MALAT1 was found upregulated in brain tissues of SAH mice and OxyHb-stimulated neurons. In addition, knockdown of MALAT1 attenuated apoptosis and decreased reactive oxygen species (ROS) production in OxyHb-stimulated neurons. Mechanistically, we demonstrated that MALAT1 bound with miR-499-5p. Furthermore, our findings indicated that miR-499-5p bound to SOX6 3' untranslated region (UTR) and negatively regulated SOX6 mRNA and protein levels. Rescue assays suggested that SOX6 overexpression counteracted the effects of MALAT1 knockdown on neurocyte apoptosis, and ROS production in OxyHb-stimulated neurons. The in vivo assays indicated that knockdown of MALAT1 improved brain injury of SAH mice. Our study demonstrates that silencing of MALAT1 alleviates neurocyte apoptosis and reduces ROS production through the miR-499-5p/SOX6 axis after SAH injury.


A switchable DNA origami/plasmonic hybrid device with a precisely tuneable DNA-free interparticle gap.
We here show a reconfigurable DNA/plasmonic nanodevice with a precisely tunable and DNA-free interparticle gap. The nanodevice comprises two DNA boxes for the size-selective incorporation of nanoparticles in a face-to-face orientation and an underlying switchable DNA platform for the controlled and reversible adjustment of the interparticle distance.


Clinical course and survival after elective splenectomy in 19 patients with primary myelofibrosis.
Nineteen patients with primary myelofibrosis and myeloid metaplasia (MMM), who fulfilled well-defined criteria, underwent elective splenectomy as soon as the diagnosis was confirmed. Nine patients developed postoperative complications such as intra-abdominal bleeding (three), rupture of the inferior vena cava (one), ascites (two), Australia antigen-positive hepatitis (three), mesenteric artery thrombosis (one) and pneumonia (one). One patient died within a month of the operation due to secondary intra-abdominal infection. The mean age of the patients at splenectomy was 56 years and the mean duration of their disease 2.4 years. The median actuarial survival after operation was 51 months. Although the series of patients is small, it seems that splenectomy did not have an adverse effect on life expectancy. The haematological status and the quality of life improved after splenectomy in 17 of 19 patients. The results warrant a further trial with elective splenectomy in an early stage of MMM.


Selectivity of reaction pathways for green diesel production towards biojet fuel applications.
Green diesel is the second generation biofuel with the same structure as fossil fuels (alkanes), allowing this biofuel to provide excellent fuel properties over biodiesel such as higher energy content and lower hazardous gas emission. Generally, green diesel can be produced through the deoxygenation/hydrogenation of natural oil and/or its derivatives at 200-400 °C and 1-10 MPa over supported metal catalysts. This process comprises of three reaction pathways: hydrodeoxygenation, decarboxylation, and decarbonylation. The extent to which these three different pathways are involved is strongly influenced by the catalyst, pressure, and temperature. Subsequently, the determination of catalyst and reaction condition plays a significant role owing to the feasibility of the process and the economic point of view. This article emphasizes the reaction pathway of green diesel production as well as the parameters influencing the predominant reaction route.


Clinical and pharmacokinetic study of 96-h infusions of doxorubicin in advanced cancer patients.
A phase I and a pharmacokinetic study of 96-h infusions of doxorubicin were performed in order to evaluate the maximum tolerated dose with this schedule of administration. Seventeen patients suffering from a digestive carcinoma were included in the study and a total of 71 courses of treatment were performed. The starting dose was 15 mg/m2/day and was increased in 2.5 mg/m2/day increments. The main toxicities observed were neutropenia and mucositis, which became limiting from 22.5 mg/m2/day (90 mg/m2 over a 96-h period); this dose was therefore defined as the maximal tolerated dose. No objective response to treatment was observed. For further studies, the recommended dose should not exceed 20 mg/m2/day. A plasma plateau concentration of doxorubicin was reached within 24 h. Despite a constant infusion rate, the plasma concentration of doxorubicin showed transient variations in several patients. However, an average plasma concentration could be evaluated for 33 courses of treatment, and this was linearly related to the dose. Doxorubicinol was the only detected metabolite of doxorubicin and its plasma concentration progressively increased throughout infusion. A detailed pharmacokinetic study was performed in 13 courses of treatment. The mean plasma clearance of doxorubicin was 25.2 l/h/m2 and the mean terminal half-lives of doxorubicin and doxorubicinol were respectively 43.6 and 66.2 h. Urinary excretion of doxorubicin plus metabolite was regular from the 24th to the 96th hour of infusion; however, the proportion of doxorubicinol progressively increased in urine. The protracted half-life of this metabolite probably explains its accumulation during infusion.


In utero ultrasonographic features of campomelic dysplasia.
A prenatal diagnosis of campomelic dysplasia in a primigravida is described. First level fetal ultrasonography demonstrated bowing and shortening of lower limbs. Second level examination allowed the correct diagnosis by demonstrating several skeletal anomalies pathognomonic of campomelic dysplasia.


Interantral alveolar ridge splitting for maxillary horizontal expansion and simultaneous dental implant insertion: A case report.
Dental implants present an advanced technique for the rehabilitation of partial or edentulous patients. Tooth loss caused by caries, periodontal disease or systemic factors often results in a decline of the bucco-lingual alveolar ridge dimension. Within one year the initial bone width can be resorbed up to 50%. As a consequence dental implants may be limited for rehabilitation and cannot be performed in a conventional manner because of the risk of dehiscence and fenestrations. Bone blocks, guided bone regeneration (GBR), horizontal osteogenic distraction and bone grafts may be used for augmentation procedures. In case of sufficient vertical bone dimension, an alveolar ridge splitting and augmentation technique (ARST) can be conducted. This case has been reported in line with PROCESS criteria [1]. We present a 51-year old female patient, who has had a full denture for about 30 years. The reason for consultation was the demand for a fixed prosthesis. Dental implants in combination of the ARST with GBR allowed us to correct horizontal deformities of the alveolar ridge. We discuss the possibility of using the ARST in the interantral region for a full arch rehabilitation of the maxilla with simultaneous dental implant placement in a narrow alveolar ridge. The ARST in addition to simultaneous implant placement with a GBR can be successfully used for a full arch rehabilitation of the maxilla in a narrow alveolar ridge.


Human natural cytotoxic lymphocytes: definition by a monoclonal antibody of a subset which kills an anchorage-dependent target cell line but not the K-562 cell line.
A monoclonal mouse antibody (HNC-1A3) which defines a subset of human lymphocytes with natural cytotoxic activity was produced and studied. HNC-1A3+ cells represent 12 +/- 3% of peripheral blood mononuclear leukocytes. When sorted out using a fluorescence-activated cell sorter, they consist of 60% small lymphocytes, 35% large (predominantly agranular) lymphocytes, and 5% monocytes. They contain 30 +/- 6% E-rosette-forming cells, 6 +/- 1% OKT4+ cells, 17 +/- 6% OKT8+ cells and less than 2% OKT10+ or Leu-7 (HNK-1)+ cells. They are responsible for most of the natural cytotoxic activity against the MA-160 prostatic adenoma cell line but mediate an insignificant amount of cytotoxicity against the NK prototype target K562 cell line. Conversely, Leu-7+ cells which mediate most NK activity against K562 are weakly active against MA-160. Our data suggest a heterogeneity among leukocytes mediating natural cytotoxicity, with restricted specificities for the recognition sites on target cells.


Cortical thickness, surface area, and gyrification abnormalities in children exposed to maltreatment: neural markers of vulnerability?
Childhood maltreatment has been shown to significantly elevate the risk of psychiatric disorder. Previous neuroimaging studies of children exposed to maltreatment have reported atypical neural structure in several regions, including the prefrontal cortex and temporal lobes. These studies have exclusively investigated volumetric differences rather than focusing on genetically and developmentally distinct indices of brain structure. Here we used surface-based methods to examine cortical thickness, surface area, and local gyrification in a community sample of children with documented experiences of abuse (n = 22) and a group of carefully matched nonmaltreated peers (n = 21). Reduced cortical thickness in the maltreated compared with the nonmaltreated group was observed in an extended cluster that incorporated the anterior cingulate, superior frontal gyrus, and orbitofrontal cortex. In addition, reduced cortical surface area was observed within the parcellated regions of the left middle temporal area and lingual gyrus. Local gyrification deficits within the maltreated group were located within two clusters, the lingual gyrus and the insula extending into pars opercularis. This is the first time structural abnormalities in the anterior cingulate and lingual gyrus have been detected in children exposed to maltreatment. Surface-based methods seem to capture subtle, previously undetected, morphological abnormalities associated with maltreatment. We suggest that these approaches detect developmental precursors of brain volume differences seen in adults with histories of abuse. Because the reported regions are implicated in several clinical disorders, they might constitute biological markers of vulnerability, linking exposure to early adversity and psychiatric risk.


Teaching in the "New Normal": Using an Evidence-Based Process to Determine Should It Stay or Should It Go (SISoSIG).
After pivoting to emergency remote instruction due to the COVID-19 pandemic, medical educators have added new techniques to their toolbox. As we welcome a "new normal," we may be able to teach even more effectively than we did before by adapting some of these techniques. This paper provides an evidence-based decision-making process for faculty to consider what should stay and what should go as they revise and enhance instruction from one semester to another. The SISoSIG process provides opportunities to reflect on lessons learned and discuss how to build on that learning to become even more effective practitioners.


Effects of inertance on respiratory mechanics measurements in mechanically ventilated children.
The use of the first-order linear single compartment model when studying respiratory mechanics classically neglects inertance (Irs). We hypothesized that Irs would affect compliance (Crs) and resistance (Rrs) estimates in mechanically ventilated young children. Prospective study; single-center evaluation. University-affiliated tertiary pediatric intensive care unit. Forty-four patients with and without respiratory disease. Patients were studied during volume-controlled constant inspiratory flow ventilation. Pressure (PaO) and flow (V') were analyzed according to two different models: a one-compartment first-order linear model according to PaO = (1/Crs) x V + Rrs x V' and a one-compartment second-order linear model according to PaO = (1/Crs) x V + Rrs x V' + Irs x V''. Irs was higher in children with vs. those without respiratory disease (median 0.00224 cm H2O/L/sec2, Q1-Q3 0.00180-0.00321 vs. median 0.00133 cm H2O/L/sec2, Q1-Q3 0.00072-0.00210; p < .001)). A positive correlation between Irs and the difference of Crs estimates between the first- and the second-order model was found in both groups (r = .84, p < .05 and r = .67, p < .05). Rrs estimates were similar in both groups. This study showed that the linear single-compartment model may not adequately estimate the respiratory mechanical properties in mechanically ventilated children, particularly in the presence of respiratory disease. Including an Irs term significantly diminished Crs estimates. A one-compartment second-order linear model might be a useful clinical tool in more adequately measuring respiratory mechanics and optimizing ventilatory settings in children with respiratory disease.


Interactions of nuclear estrogen receptor with DNA and RNA.
The interaction of the nuclear estrogen receptor from hen oviduct with nucleic acids were studied by competition assay using DNa-cellulose centrifugation. We demonstrated that the estradiol-receptor complex binds similarly well to poly(A) RNA and denatured DNA. The estrogen receptor was found to interact more strongly with poly(G), poly(U) than with poly(A), poly(C). The receptor complex binds similarly to poly(A) and poly(dA), and to poly(U) and poly(dU). However, the receptor complex shows stronger binding to poly(G) than to poly(dG) and to poly(C) than to poly(dC). Studies with heteropolyribonucleotides indicated that poly(U1G1) is more effective in competing for the estrogen receptor, and poly(AC) and poly(AUG) are moderately effective, whereas poly(ACU) is least effective. GMP and dGMP showed some competition for the nuclear receptor at 300-fold higher nucleotide concentrations than that of the synthetic poly(G). Observations that the nuclear estrogen receptor binds to poly(A) RNA and interacts selectively with polyribonucleotides suggest that the estrogen receptor-RNA interaction may play a role for the function of estrogens in gene regulation.


Complex local dynamics in DNA on the picosecond and nanosecond time scales.
Time-resolved Stokes shift measurements of the local structural relaxation of three DNA oligonucleotides are presented. Logarithmic relaxation is seen for over three decades in time (40 ps-40 ns), indicating a complex relaxation among a large number of conformational substates. The observed relaxation is the same in all the sequences. Sequence dependence of the localized dynamics of DNA does not appear within this time range. We infer that 30%-50% of the relaxation is faster than 40 ps, has a nonlogarithmic decay and has a sequence dependent amplitude.


Protein SUMOylation regulates insulin secretion at multiple stages.
Type-II Diabetes Mellitus (T2DM) is one of the fastest growing public health issues of modern times, consuming 12% of worldwide health budgets and affecting an estimated 400 million people. A key pathological trait associated with this disease is the failure of normal glucose-stimulated insulin secretion (GSIS) from pancreatic beta cells. Several lines of evidence suggest that vesicle trafficking events such as insulin secretion are regulated by the post-translational modification, SUMOylation, and indeed SUMOylation has been proposed to act as a 'brake' on insulin exocytosis. Here, we show that diabetic stimuli which inhibit GSIS are correlated with an increase in cellular protein SUMOylation, and that inhibition of deSUMOylation reduces GSIS. We demonstrate that manipulation of cellular protein SUMOylation levels, by overexpression of several different components of the SUMOylation pathway, have varied and complex effects on GSIS, indicating that SUMOylation regulates this process at multiple stages. We further demonstrate that inhibition of syntaxin1A SUMOylation, via a knockdown-rescue strategy, greatly enhances GSIS. Our data are therefore consistent with the model that SUMOylation acts as a brake on GSIS, and we have identified SUMOylation of syntaxin 1 A as a potential component of this brake. However, our data also demonstrate that the role of SUMOylation in GSIS is complex and may involve many substrates.


Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.
RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials.


Increased susceptibility to injury and normal reactivity to prostaglandin protection of mucous cells isolated from gastric mucosa of portal hypertensive rats.
We examined the susceptibility of mucous cells isolated from gastric mucosa of portal hypertensive rats to ethanol injury. In addition, we assessed their response to protective action of prostaglandin against ethanol injury in vitro. Ethanol significantly decreased cell viability in calcium-containing medium. The injury of mucous cells isolated from portal hypertensive rats was more extensive than those isolated from sham-operated rats. Ethanol-induced cell injury was reduced similarly in both groups by pretreatment with 16,16-dimethyl prostaglandin E2. These results suggest that mucous cells isolated from portal hypertensive gastric mucosa are more susceptible to ethanol injury and this susceptibility is dependent on extracellular calcium. The cells from portal hypertensive gastric mucosa retain, however, sensitivity to protective action of 16,16-dimethyl prostaglandin E2.


[Clinical study on treatment of atopic dermatitis by integrated traditional Chinese and Western medicine].
To observe the clinical effects and explore the mechanism of the integrated traditional Chinese and Western medicine in treating atopic dermatitis (AD). Forty-seven patients with AD were randomly assigned to two groups, the control group and the treated group, they were treated with conventional Western medicine (10 mg Loratadine tablet, once daily) and with integrated medicine additionally given modified Jiawei Danggui Decection besides Western medicine respectively for 4 weeks. Double-sandwich ELISA was used to detect the levels of interleukin- 4, -10 and -12 (IL-4, IL-10 and IL-12) before and after treatment. The total effective rate in the treated group was 56% (14/25 cases), better than that in the control group (22.7%, 5/22 cases), showing significant difference between the two groups (X2 = 5.38, P < 0.05). Before treatment the serum levels of IL-4, IL-10 were significantly higher and level of IL-12 was lower in AD patients as compared with those in healthy persons (P < 0.01); they all restored to normal in the treated group after treatment but unchanged in the control group, showing significant difference between the two groups (P < 0.01). The clinical effect of integrated traditional Chinese and Western medicine is ascertainable, its mechanism might be associated with the regulation on related cytokines.


Regulation of CXCR4/AKT-signaling-induced cell invasion and tumor metastasis by RhoA, Rac-1, and Cdc42 in human esophageal cancer.
CXC chemokines and their cognate receptors have been implicated wildly in cancer pathogenesis. In the present study, we report a critical cause relationship between CXCR4 expression and tumorigenesis in the setting of human esophageal squamous cell carcinoma (ESCC). In ESCC cells, CXCR4 expression was significantly higher than in human esophageal epithelial cells (HEEC). Reduction of CXCR4 in ESCC cells reduced cell proliferation and invasion in vitro and tumor growth in vivo. Among the potential downstream targets of CXCR4-CXCL12 are RhoA, Rac-1, and Cdc42, which are likely to contribute to the invasiveness of ESCC cells. Finally, we found that CXCR4-CXCL12/AKT axis regulates RhoA, Rac-1, and Cdc42 to modulate cell invasion and tumor metastasis. Together, these results demonstrate a role for CXCR4 in ESCC metastasis and progression and suggest potential targets for therapeutic intervention.


The aftermath of suicide on the psychiatric inpatient unit.
Suicide in the hospital setting results in a complex array of reactions by the staff, the institution, the remaining patients, the family of the patient, and the outpatient caregivers. In the aftermath of a suicide survivors pass through four predictable and parallel stages: shock, recoil, posttrauma, and recovery. Specific approaches to these stages are addressed. The management of the shock phase requires carefully orchestrated crisis-intervention strategies, containment, and risk management. The numbness and disbelief of this period gives way to the reactions of the recoil phase, which include guilt, shame, anger, depression, self-doubt, and a search for meaning. Group meetings, outreach to the family, the suicide review conference, and, in particular, informal peer contact, are key aspects of recovery in this stage. Family survivors require specialized interventions that take into account the stigmatization that commonly accompanies suicide. In addition, as one fourth to one third of hospital suicides result in lawsuits, specialized approaches to assessment and documentation are indicated. In the posttraumatic phase more general issues of professional efficacy are addressed. The resolution of this phase is enhanced by an open dialogue focusing on the limitations of assessment and treatment of the suicidal patient. Final recovery for staff includes a posture of anticipation appropriate to the clinical setting.


Screening and identification of multi-component in Qingkailing injection using combination of liquid chromatography/time-of-flight mass spectrometry and liquid chromatography/ion trap mass spectrometry.
An approach for screening and identification of multi-component in complex traditional Chinese medicine systems with a combinative LC/MS (MS(n)) technique was described in this paper. The chemical profile of Qingkailing injection, a well-known traditional Chinese formula in China, was studied using the established method as for an application. Benefit from combining the accurate mass measurement of LC/TOF-MS to generate elemental compositions and the complementary multilevel structural information provided by LC/ion trap MS(n), 33 components in Qingkailing injection were identified in all. The three isomers of chlorogenic acid, isochlorogenic acid and neochlorogenic acid which are derived from Flos Lonicerae, one of the medicinal materials in Qingkailing, were differentiated by verifying their MS3 fragmentation data. All the components identified were surveyed and classified according to their medicinal materials derivation. This study is expected to provide an effective and reliable pattern for comprehensive and systematic characterization of the complex traditional Chinese medicine systems.


Cloning, expression, purification and biochemical characterization of the recombinant chitinase enzyme encoded by CTS2 in the budding yeast.
Chitin is a polymer of β-1,4-linked N-acetylglucosamine (GlcNAc) and plays a central role in the assembly of the fungal cell wall. Chitinases are hydrolytic enzymes that break down glycosidic bonds in the chitin. Chitinases are classified into three categories, endochitinases, exochitinases and N-acetylglucosaminases, according to the manner in which the enzyme cleaves the chitin polymer. Saccharomyces cerevisiae has two chitinase-encoding genes, CTS1 and CTS2. However, whether Cts2p shows a chitinase activity remains unknown. In this study, we have cloned, expressed and purified the recombinant Cts2p protein from bacterial cells. We have demonstrated that Cts2p has a higher chitobiosidase (exochitinase) activity than endochitinase activity, but no N-acetylglucosaminase activity. The optimal temperature for the chitobiosidase activity of Cts2p is 37 °C.


Pyoderma gangrenosum following isotretinoin therapy for acne nodulocystic.
A 19-year-old man with nodulocystic acne on baseline was treated with isotretinoin therapy. After 1 month on the medication, he developed pyoderma gangrenosum on his pubis area, arms and legs, and pathergy on a puncture site. Possible underlying diseases were excluded. The patient was started on steroids (prednisone 1 mg/kg/d) and isotretinoin therapy was withdrawn. Later the prednisone was tapered and dapsone 100 mg/daily was initiated. After 10 months of follow-up all lesions had healed and no underlying diseases developed.


Inflammation and melanoma growth and metastasis: the role of platelet-activating factor (PAF) and its receptor.
An inflammatory tumor microenvironment fosters tumor growth, angiogenesis and metastatic progression. Platelet-activating factor (PAF) is an inflammatory biolipid produced from membrane glycerophospholipids. Through the activity of its G-protein coupled receptor, PAF triggers a variety of pathological reactions including tumor neo-angiogenesis. Several groups have demonstrated that inhibiting PAF-PAF receptor pathway at the level of a ligand or receptor results in an effective inhibition of experimental tumor growth and metastasis. In particular, our group has recently demonstrated that PAF receptor antagonists can effectively inhibit the metastatic potential of human melanoma cells in nude mice. Furthermore, we showed that PAF stimulated the phosphorylation of CREB and ATF-1 in metastatic melanoma cells, which resulted in overexpression of MMP-2 and MT1-MMP. Our data indicate that PAF acts as a promoter of melanoma metastasis in vivo. Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that these cells are better equipped to respond to PAF within the tumor microenvironment when compared to their non-metastatic counterparts.


[Neuroradiological examination of the intracranial visual pathway. Part I].
The clinical symptoms of lesions affecting the intracranial visual pathway vary as widely as their aetiology. The anatomy, the basics of neuro-ophthalmology and MRI protocols are touched on in the first part of this serial paper; in addition the most important pathological entities affecting the sellar region are presented. The focus is on the differentiation between extrinsic and intrinsic lesions, but in addition to this vascular lesions are presented with reference to illustrative cases.


Production of bioactive conjugated linoleic acid by the multifunctional enolase from Lactobacillus plantarum.
Lactobacillus plantarum α-enolase, a multifunctional-anchorless-surface protein belonging to the conserved family of enolases with a central role in glycolytic metabolism, was characterized to have a side role in the intricate metabolism of biohydrogenation of linoleic acid, catalyzing the formation of bioactive 9-cis-11-trans-CLA through dehydration and isomerization of 10-hydroxy-12-cis-octadecenoic acid. The identity of the enolase was confirmed through mass spectrometric analysis that showed the characteristic 442 amino acid sequence with a molecular mass of 48.03kDa. The enolase was not capable of using linoleic acid directly as a substrate but instead uses its hydroxyl derivative 10-hydroxi-12-cis-octadecenoic acid to finally form bioactive conjugated linoleic acid. Biochemical optimization studies were carried out to elucidate the conditions for maximum production of 9-cis-11-trans-CLA and maximum stability of α-enolase when catalyzing this reaction. Furthermore, through structural analysis of the protein, we propose the binding sites of substrate and product molecules that were characterized as two hydrophobic superficial pockets located at opposite ends of the enolase connected through a channel where the catalysis of dehydration and isomerization might occur. These results prove that multifunctional α-enolase also plays a role in cell detoxification from polyunsaturated fatty acids such as linoleic acid, along with the linoleate isomerase complex.


Scorpion toxins from Tityus cambridgei that affect Na(+)-channels.
By means of high performance liquid chromatography (HPLC) the soluble venom of the Amazonian scorpion Tityus cambridgei was fractionated into over 50 different components. Four toxic and/or lethal peptides to mice were obtained in pure form and sequenced. Mass spectrometry analysis showed molecular weights of 7310, 7151, 7259 and 7405, respectively, for toxins Tc48a, Tc49a, Tc54 and Tc49b. The N-terminal amino acid sequence was obtained for the three first toxins mentioned, whereas the full primary structure was determined for Tc49b. It contains 64 amino acid residues, closely packed by four disulfide bridges. Sequence comparison analysis showed similarities around 50% with other toxins from scorpions of the genus Tityus of Brazil. It is lethal to mice at doses of 20 microg per 20 g mouse. The toxin was shown to affect the Na(+)-currents permeability of rat cerebellum granular cells in culture. Almost a complete elimination of current was observed with 100 nM toxin concentration. This effect was partially reversible. Furthermore, this toxin does not modify the function of the Shaker B K(+)-channels expressed on Sf9 cells, nor does it modify the Na(+)-channel function in a similar manner as those reported for the alpha-scorpion toxins purified from other scorpions.


Immunity and Alzheimer's disease: immunological perspectives on the development of novel therapies.
Alzheimer's disease (AD) is the most common neurodegenerative disorder among older people. However, no cure or disease-modifying treatments are currently available, and the molecular and cellular mechanisms responsible for the etiology of AD remain under debate. Recent studies suggest that the immune system has a crucial role in AD pathogenesis and, thus, immunotherapy might be a promising new treatment. Here, we review the roles of the immune system in AD pathogenesis as well as recent developments in immunotherapy for AD. Furthermore, we hypothesize that age-related immune dysregulation, which might be a consequence of the age-associated chronic inflammation known as 'inflammaging', significantly contributes to AD pathogenesis. Finally, we propose various immunological mechanisms for the development of safe and effective therapies for AD.


Acute effect of metformin on exercise capacity in active males.
Physical activity and metformin are often used concomitantly in the treatment of diabetes, even though little is known about possible interactions between these treatment modalities. This study was designed to examine the acute effect of metformin on oxygen consumption and lactate concentration during exercise. Eleven healthy, active men [mean +/- s.d.: age = 29.9 +/- 3.7 years; body mass index = 25.2 +/- 2.8 kg/m2; maximal oxygen consumption (VO2max) = 53.5 +/- 8.9 ml/kg/min] completed a randomized, double-blind, placebo-controlled, crossover study. The testing protocol consisted of a standardized breakfast with metformin (1000 mg) or placebo. Three hours after breakfast, participants underwent a graded maximal exercise test on a cycle ergometer. Approximately 30 min after this exercise test, participants cycled continuously at an intensity below their ventilatory threshold for 45 min (mean exercise intensity = 69 +/- 5.5% of VO2max). During the graded exercise test, average oxygen consumption was higher for the metformin condition (2.9 vs. 2.8 l/min, p = 0.04); however, there was no treatment effect on VO2max or ventilatory threshold. During continuous exercise, lactate was lower for the metformin condition (4.7 vs. 5.4 mmol/l, p = 0.05). Following a standardized lunch, glucose concentrations were lower in the metformin compared with the placebo condition (5.8 vs. 6.4 mmol/l, p = 0.04). A single dose of metformin does not acutely influence maximal oxygen consumption or ventilatory threshold in healthy active males. The lower lactate concentration observed during continuous exercise with metformin was an unexpected finding considering that, in the resting state, metformin has been previously associated with a modest increase in lactate concentrations.


Incomplete cellular depopulation may explain the high failure rate of bovine ureteric grafts.
The aim was to assess the results of a decellularized bovine ureter graft (SynerGraft) for complex venous access. Bovine ureter conduits were implanted in patients with a failed fistula or access graft in whom native vessels were unsuitable as conduits. Graft histories were obtained from all patients who had undergone this procedure at one institution. Failed grafts were explanted and subjected to histological examination. A sample of fresh bovine ureter was immunostained for galactose (alpha1 --> 3) galactose (alpha-Gal). Nine patients with a median age of 46 (range 25-70) years underwent complex venous access surgery between August 2004 and November 2006 using a SynerGraft. Graft types included loop superficial femoral artery to stump of long saphenous vein (four patients), loop brachial artery to vein (two), brachial artery to axillary vein (two) and left axillary artery to innominate vein (one). Three grafts developed aneurysmal dilatation and two thrombosed. Histological assessment of the explanted bovine ureters revealed acute and chronic transmural inflammation. Immunostaining of fresh bovine ureter suggested residual cells and the xenoantigen alpha-Gal. Graft failure with aneurysmal dilatation and thrombosis in complex arteriovenous conduits using bovine ureter may be due to residual xenoantigens.


Emergency Department Grief Support: A Multidisciplinary Intervention to Provide Bereavement Support After Death in the Emergency Department.
The nature of death in the emergency department (ED) may put survivors at higher risk for complicated bereavement. Access to bereavement care could mitigate this, but many EDs do not include bereavement follow-up as part of their routine practice. We describe the implementation at our institution of ED Grief Support, a program developed to extend care to the bereaved through in-person, telephone, and e-mail follow-up for 1 year after the death of a loved one. Bereavement follow-up was preferentially extended to survivors of patients <45 years of age who were chosen because of the higher likelihood of unexpected death in this age group. Detailed records of each case were collected prospectively using online data management software and outcomes were recorded. Successful strategies to navigate communication and resource referrals are discussed. We enrolled 192 patients during our 2-year period of observation. The majority died from trauma and parents were the most common next-of-kin to be contacted. Commonly requested services included: clarification of the circumstances of death, the interpretation of autopsy reports, referral to community bereavement resources, and family meetings. Challenges included supporting the emotional well-being of staff and the resource-intensive nature of the follow-up. Staff members who worked with ED Grief Support find it meaningful and note a positive influence on their well-being as providers. Longitudinal bereavement follow-up from the ED is feasible and had a perceived positive impact on the bereaved as well as ED staff.


Concomitant Medial and Lateral Meniscus Posterior Horn Root Repair With ACL Reconstruction Using Trans-Tibial Tunnel Technique.
Concomitant medial meniscus posterior horn root tears and lateral meniscus posterior horn root tears are rare in occurrence. There is limited literature on the simultaneous repair of medial and lateral meniscus root tears, with ACL reconstruction. We discuss management of concomitant medial meniscus posterior horn root tear (MMPHRT), lateral meniscus posterior horn root tear (LMPHRT), and anterior cruciate ligament (ACL) tear. We highlight the surgical technique in which we perform a repair of both medial and lateral meniscus posterior horn root repairs with ACL reconstruction. We explain the sequence of such a repair to avoid tunnel coalescence.


Reducing antimicrobial resistance by practicing better infection prevention and control.
This article summarizes an event hosted on the sidelines of the 77th session of the United Nations General Assembly (UNGA) to discuss the impact of the COVID-19 pandemic on antimicrobial resistance.


Novel isolation and purification method permitting functional cytotoxicity studies of macrophages from milky spots in the greater omentum.
Milky spots in the greater omentum are well organized perivascular infiltrates of leukocytes which are probably involved in the clearance of tumor cells from the peritoneal cavity. In milky spots, macrophages are the predominant cell type forming a distinct population of cells. To investigate whether these macrophages have a function in the control of metastatic spread in the peritoneal cavity, a novel isolation and purification method was developed in order to study the functional cytotoxicity of macrophages from milky spots in the greater omentum against tumor cells in vitro. In order to obtain a cell suspension, greater omenta of unstimulated healthy male WAG/RIJ rats were incubated in collagenase/DNase suspension and filtered. Subsequently, macrophages were isolated and purified using flow cytometry by sorting unstained cells on the basis of size and internal complexity. Macrophages and other cells were identified by routine May-Grünwald-Giemsa staining and by immunophenotyping with the specific macrophage monoclonal antibody ED 1. Furthermore, macrophage subtypes were characterized by ultrastructural analysis. Functional cytotoxicity of the isolated macrophages was assayed against the syngeneic CC 531 tumor cell line in a colorimetric MTT assay. From three greater omenta of healthy rats 1.16 +/- 0.16 x 10(6) macrophages were isolated with a purity of 83 +/- 2% and a viability of > or = 96%. The macrophages were of the exudate (monocytic), exudate-resident and resident cell type and were in equal proportions. The contaminating cells were mainly mesothelial. A maximum cytotoxicity of approximately 30% was reached with the macrophage fraction at an effector-to-target ratio of 10. Furthermore, it was established that the mesothelial cells did not exhibit cytotoxicity.


miR-330 regulates the proliferation of colorectal cancer cells by targeting Cdc42.
MicroRNAs are small non-coding RNA molecules that play important roles in the multistep process of colorectal carcinoma (CRC) development. However, the miRNA-mRNA regulatory network is far from being fully understood. The objective of this study was to investigate the expression and the biological roles of miR-330 in colorectal cancer cells. Cdc42, one of the best characterized members of the Rho GTPase family, was found to be up-regulated in several types of human tumors including CRC and has been implicated in cancer initiation and progression. In the present study, we identified miR-330, as a potential regulator of Cdc42, was found to be inversely correlated with Cdc42 expression in colorectal cancer cell lines. Ectopic expression of miR-330 down-regulated Cdc42 expression at both protein and mRNA level, mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest and apoptosis of the colorectal cancer cells, whereas restoration of Cdc42 could partially attenuate the effects of miR-330. In addition, elevated expression of miR-330 could suppress the immediate downstream effectors of Cdc42 and inhibit the growth of colorectal cancer cells in vivo. To sum up, our results establish a role of miR-330 in negatively regulating Cdc42 expression and colorectal cancer cell proliferation. They suggest that manipulating the expression level of Cdc42 by miR-330 has the potential to influence colorectal cancer progression.


Efficiency of Soil Amendments for Copper Removal and Brassica Juncea (L.) Growth in Wastewater Irrigated Agricultural Soil.
Wastewater irrigation is becoming a massive challenge for sustainable agriculture. Particularly, copper (Cu) presence in wastewater poses a great threat to the food chain quality. Thus, scientists need to address this issue by using chemical and organic soil amendments to restore the soil ecosystem. Therefore, this study aims to examine the efficacy of sulphur, compost, acidified animal manure and sesame straw biochar for Cu immobilization, adsorption and Brassica growth in wastewater irrigated soil. The current findings presented that all the soil amendments prominently improved brassica yield and significantly minimized the Cu uptake by Brassica shoots and roots in sesame straw biochar (SB) (64.2% and 50.2%), compost (CP) (48% and 32.5%), acidified manure (AM) (37% and 23.2%) and Sulphur (SP) (16% and 3.1%) respectively relative to untreated soil. In addition, Cu bioavailability was reduced by 51%, 34%, 16.6%, and 7.4% when SB, CP, AM, and SP were incorporated in wastewater irrigated polluted soil. The Cu adsorption isotherm results also revealed that SB treated soil has great potential to increase Cu adsorption capacity by 223 mg g- 1 over control 89 mg g- 1. Among all the treatments, SB and CP were considered suitable candidates for the restoration of Cu polluted alkaline nature soil.


Precision in calculated rho, T1 and T2 images as a function of data analysis method.
In NMR imaging rho, T1 and T2 images are usually calculated from a set of partial saturation, saturation recovery or inversion recovery experiments with multiple echoes and multiple repetition times. Several methods can be envisaged to extract parameter images from such a set of source images. These methods to a greater or lesser extent take advantage of the fact that a multiple echo/multiple repetition time experiment provides a set of largely independent T1 and T2 measurements. In this study several data analysis methods, including weighted and non-weighted averaging of results of independent T1 and T2 measurements, weighted and non-weighted averaging of source images prior to data reduction and simultaneous three-parameter fitting, were compared against another in terms of precision, computational efficiency and robustness. The predicted performance of the examined methods was verified by stochastic simulation experiments.


A high-affinity folate binding protein in human urine. Radioligand binding characteristics, immunological properties and molecular size.
High-affinity binding of [3H]folate in human urine displayed characteristics, e.g. apparent positive cooperativity, which are typical of specific folate binding. By means of a two-site enzyme-linked immunosorbent assay (ELISA) with rabbit antibodies against the low molecular weight folate binding protein from human milk, we measured folate binding protein concentrations in the range of 0.51 to 4.13 nM in urine samples from 16 apparently healthy individuals. Ultrogel AcA 44 chromatography of the urine showed that immunoreactive and radioligand bound folate binding protein coeluted in one large peak (Mr approximately 25,000).


Conductive magnetite nanoparticles trigger syntrophic methane production in single chamber microbial electrochemical systems.
Performance of methane-producing microbial electrochemical systems (MESs) is highly reliant on electron transfer efficiency from electrode to microorganisms and vice versa. In this study, magnetite nanoparticles were used as electron carriers to enhance extracellular electron transfer in single chamber MESs. The MES with magnetite exhibited the highest methane yield and current generation of 0.37 ± 0.009 LCH4/gCOD and 9.6 mA, respectively among the tested reactors. The experimental data was observed to be highly consistent with modified Gompertz model results (R2 > 0.99), which also showed 74.2% and 22.1% enhanced methane production rate in MES with magnetite as compared to control AD and MES without magnetite, respectively. Cyclic voltammetry and electrochemical impedance spectroscopy analysis confirmed that magnetite enhanced catalytic activity of biofilm and lowered both solution and charge transfer resistance. Therefore, supplementing magnetite in MESs could be a strategy to develop an efficient syntrophic biomethanation in field scale applications.


Invasive breast cancer: correlation of dynamic MR features with prognostic factors.
The purpose of this exploratory study was to correlate kinetic and morphologic MR features with histologic prognostic factors in invasive breast cancer. Sixty-one women with invasive breast cancer underwent dynamic contrast-enhanced MR imaging at 1.5 T, using T1-weighted 3D fast low-angle shot technique. The MR characteristics were correlated with classical pathologic prognostic factors (tumor size, histologic type, grade and lymph node status) and immunohistochemically detected biomarkers [c-erbB-2, p53, Ki-67, and estrogen receptor (ER)]. Univariate and multivariate statistical analyses were performed. Presence of rim enhancement pattern, early maximal enhancement and washout phenomenon were independently associated with established predictors of poor prognosis (higher histologic grade, positive Ki-67, and negative ER status). Our results suggest that these MR signs are not only important in differentiating benign from malignant lesions, but may also be useful to noninvasively identify highly aggressive breast carcinomas.


Pattern formation in the striatum: developmental changes in the distribution of striatonigral projections.
The mammalian striatum (the major subcortical structure in the telencephalon) can be divided into two compartments, the patch and the matrix, on the basis of various neurochemical and hodological markers expressed in the adult. The primary efferent target of striatal neurons is the substantia nigra. We have previously shown that the patch compartment sends projections to the substantia nigra embryonically; whereas the matrix does not form a similar projection until the early postnatal period (Fishell and van der Kooy, J. Neurosci., 7 (1987) 1969-1978). The projection of patch neurons to the substantia nigra is the earliest developmental marker for the patch compartment. Here we ask about the early distribution of patch projections and their possible relation to striatal compartmentalization. Embryonic anterograde axonal tracing of the striatonigral pathway can take advantage of the temporal separation of patch versus matrix projections to reveal the terminal distribution of patch striatonigral neurons independent of the nigral terminal distribution from the striatal matrix. The anterograde tracer rhodamine isothiocyanate was shown in a model system to persist in labeled neurons for more than a week, but to be available for uptake into these neurons for a few days after injection at the most. These properties of rhodamine isothiocyanate were combined experimentally with short and long term survival periods. This allowed assessment of the changing developmental distribution of nigral fibers from specifically the striatal patch compartment. In all experimental cases the anterogradely labeled sections of the substantia nigra were also stained with antibodies to tyrosine hydroxylase, which permitted differentiation of the dopamine cell rich pars compacta from the dopamine cell poor pars reticulata. The results show that in the adult the majority of patch and matrix striatonigral projections are confined to the substantia nigra pars reticulata. Furthermore, their fiber distribution within the pars reticulata is overlapping rather than complementary. Most interestingly, in the late embryonic period (most noticeably at embryonic day 19) there is a marked overlap between patch striatonigral fibers and nigral dopamine perikarya. By early postnatal times, when the matrix compartment begins to form its striatonigral projection, the overlap of patch striatonigral fibers and dopamine cells has largely disappeared. The results suggest that a transient interaction between patch striatonigral fibers and dopamine neurons (which is concomitant with the formation of striatal compartments), may be an important developmental event in the phenotypic maturation of striatal pa


The neurobiology of binge-like ethanol drinking: evidence from rodent models.
Binge alcohol (ethanol) drinking is a destructive pattern of ethanol consumption that may precipitate ethanol dependence-a chronic, debilitating, and prevalent health problem. While an abundance of research has focused on the neurochemical underpinnings of ethanol dependence, relatively little is known about the mechanisms underlying the heavy consumption characteristic of binge ethanol drinking. Recently, a simple preclinical model termed "drinking in the dark" (DID) was developed to examine binge-like ethanol consumption in a rodent population. This assay capitalizes on the predisposition of C57BL/6J mice to voluntarily consume substantial quantities of a high concentration (20% v/v) ethanol solution, resulting in pharmacologically relevant blood ethanol concentrations (BECs). This review provides a comprehensive overview of recent literature utilizing this model to investigate the neuromodulatory systems that may influence binge ethanol drinking. Studies examining the glutamatergic and opioidergic systems not only provide evidence for these systems in the modulation of binge-like ethanol consumption, but also suggest this preclinical model has predictive validity and may be an appropriate tool for screening novel pharmacological compounds aimed at treating binge ethanol drinking in the human population. Additionally, this review presents evidence for the involvement of the GABAergic, dopaminergic, nicotinic, and endocannabinoid systems in modulating binge-like ethanol consumption. Finally, recent evidence shows that corticotropin-releasing factor (CRF), agouti-related protein (AgRP), neuropeptide Y (NPY), and ghrelin are also implicated as impacting this pattern of ethanol consumption.


Complex coacervation of scallop (Patinopecten yessoensis) male gonad hydrolysates and κ-carrageenan: Effect of NaCl and KCl.
The complex coacervation between scallop Patinopecten yessoensis male gonad hydrolysates (SMGHs) and κ-carrageenan (κ-C) as influenced by ionic strength (NaCl and KCl) were monitored by using turbidimetric analysis at pH 1-12. The optical density of SMGHs/κ-C complexes initially increased at lower ionic strength (0-0.5 M) whereas decreased at higher ionic strength (0.5-1.5 M) as a result of the salt-enhanced and salt-reduced effect, respectively. Both of pHc and pHφ1 exhibited ionic strength-dependent behavior that firstly shifted to acidic pH followed by an increase as salt increasing. Moreover, salt addition strongly promoted the gelation of SMGHs/κ-C which was mainly driven by electrostatic forces, as reflected by increasing storage modulus G' from 3621 to 6559 Pa, 2681-25631 Pa at 0.1 Hz and decreasing T23 relaxation time from 349.10 to 296.89 ms, 241.07-186.89 ms by 0-0.5 M NaCl/KCl, respectively. Furthermore, the rheological and relaxation time T2 data were well associated with microscopy images that SMGHs/κ-C gels with NaCl/KCl showed a denser network with more flocculation formation and larger pore sizes with thicker network wall, especially in KCl group, which indeed supported the gel elasticity. Taken together, this study could provide theoretical and methodological basis for new functional hydrogel products with modified gel strength and microstructure by understanding the complex coacervation in gel system.


CT pattern of Infarct location and not infarct volume determines outcome after decompressive hemicraniectomy for Malignant Middle Cerebral Artery Stroke.
Malignant middle cerebral artery [MMCA] infarction has a different topographic distribution that might confound the relationship between lesion volume and outcome. Retrospective study to determine the multivariable relationship between computerized tomographic [CT] infarct location, volume and outcomes in decompressive hemicraniectomy [DHC] for MMCA infarction. The MCA infarctions were classified into four subgroups by CT, subtotal, complete MCA [co-MCA], Subtotal MCA with additional infarction [Subtotal MCAAI] and co-MCA with additional infarction [Co-MCAAI]. Maximum infarct volume [MIV] was measured on the pre-operative CT. Functional outcome was measured by the modified Rankin Scale [mRS] dichotomized as favourable 0-3 and unfavourable ≥4, at three months. In 137 patients, from least favourable to favourable outcome were co-MCAAI, subtotal MCAAI, co-MCA and subtotal MCA infarction. Co-MCAAI had the worst outcome, 56/57 patients with additional infarction had mRS ≥ 4. Multiple comparisons Scheffe test showed no significant difference in MIV of subtotal infarction, co-MCA, Subtotal MCAAI but the outcome was significantly different. Multivariate analysis confirmed MCAAI [7.027 (2.56-19.28), p = 0.000] as the most significant predictor of poor outcomes whereas MIV was not significant [OR, 0.99 (0.99-01.00), p = 0.594]. Other significant independent predictors were age ≥ 55 years 12.14 (2.60-56.02), p = 0.001 and uncal herniation 4.98(1.53-16.19), p = 0.007]. Our data shows the contribution of CT infarction location in determining the functional outcome after DHC. Subgroups of patients undergoing DHC had different outcomes despite comparable infarction volumes.