A virtual deliberative public engagement study on heritable genome editing among South Africans: Study protocol.
This article outlines the protocol for a prospective study for virtual deliberative public engagement on heritable genome editing in humans. The study intends to create a platform for a diverse group of 25-30 South Africans to engage with a facilitator and each other on 15 policy questions regarding heritable genome editing, with a focus on: a) the prevention of heritable genetic conditions; b) editing for immunity; and c) editing for enhancement. The aim is to understand the views on these issues so as to inform further research and policy, and to analyse the process and effect of deliberation on opinion. Participants will be expected to study the provided resource materials and pass the entrance exam-aligning with the protocols of the Harvard Personal Genome Project. In this way, the commitment, openness and basic knowledge of the candidates will be tested to ascertain whether they are suitable participants for the deliberative engagement.


Functional responses modified by predator density.
Realistic functional responses are required for accurate model predictions at the community level. However, controversy remains regarding which types of dependencies need to be included in functional response models. Several studies have shown an effect of very high predator densities on per capita predation rates, but it is unclear whether this predator dependence is also important at low predator densities. We fit integrated functional response models to predation data from 4-h experiments where we had varied both predator and prey densities. Using an information theoretic approach we show that the best-fit model includes moderate predator dependence, which was equally strong even at low predator densities. The best fits of Beddington-DeAngelis and Arditi-Akçakaya functional responses were closely followed by the fit of the Arditi-Ginzburg model. A Holling type III functional response did not describe the data well. In addition, independent behavioral observations revealed high encounter rates between predators. We quantified the number of encounters between predators and the time the focal predator spent interacting with other individuals per encounter. This time "wasted" on conspecifics reduced the total time available for foraging and may therefore account for lower predation rates at higher predator densities. Our findings imply that ecological theory needs to take realistic levels of predator dependence into account.


Video-Based Educational Interventions for Patients With Chronic Illnesses: Systematic Review.
With rising time constraints, health care professionals increasingly depend on technology to provide health advice and teach patients how to manage chronic disease. The effectiveness of video-based tools in improving knowledge, health behaviors, disease severity, and health care use for patients with major chronic illnesses is not well understood. The aim of this study was to assess the current literature regarding the efficacy of video-based educational tools for patients in improving process and outcome measures across several chronic illnesses. A systematic review was conducted using CINAHL and PubMed with predefined search terms. The search included studies published through October 2021. The eligible studies were intervention studies of video-based self-management patient education for an adult patient population with the following chronic health conditions: asthma, chronic kidney disease, chronic obstructive pulmonary disease, chronic pain syndromes, diabetes, heart failure, HIV infection, hypertension, inflammatory bowel disease, and rheumatologic disorders. The eligible papers underwent full extraction of study characteristics, study design, sample demographics, and results. Bias was assessed with the Cochrane risk-of-bias tools. Summary statistics were synthesized in Stata SE (StataCorp LLC). Data reporting was conducted per the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. Of the 112 studies fully extracted, 59 (52.7%) were deemed eligible for inclusion in this review. The majority of the included papers were superiority randomized controlled trials (RCTs; 39/59, 66%), with fewer pre-post studies (13/59, 22%) and noninferiority RCTs (7/59, 12%). The most represented conditions of interest were obstructive lung disease (18/59, 31%), diabetes (11/59, 19%), and heart failure (9/59, 15%). The plurality (28/59, 47%) of video-based interventions only occurred once and occurred alongside adjunct interventions that included printed materials, in-person counseling, and interactive modules. The most frequently studied outcomes were disease severity, health behavior, and patient knowledge. Video-based tools were the most effective in improving patient knowledge (30/40, 75%). Approximately half reported health behavior (21/38, 56%) and patient self-efficacy (12/23, 52%) outcomes were improved by video-based tools, and a minority of health care use (11/28, 39%) and disease severity (23/69, 33%) outcomes were improved by video-based tools. In total, 48% (22/46) of the superiority and noninferiority RCTs and 54% (7/13) of the pre-post trials had moderate or high risk of bias. There is robust evidence that video-based tools can improve patient knowledge across several chronic illnesses. These tools less consistently improve disease severity and health care use outcomes. Additional study is needed to identify features that maximize the efficacy of video-based interventions for patients across the spectrum of digital competencies to ensure optimized and equitable patient education and outcomes.


Molecular Genetic Characteristics of Plasmid-Borne mcr-9 in Salmonella enterica Serotype Typhimurium and Thompson in Zhejiang, China.
Salmonella enterica is a zoonotic food-borne pathogen threatening public health around the world. As is the case with many other pathogens, the spread of mobilized colistin resistance (mcr) alleles is of grave concern. In this study, totally 689 clinical Salmonella isolates were collected from a local hospital in Hangzhou, Zhejiang Province, China between 2009 and 2018. Resistance genes were screen by PCR. Two mcr-9-positive Salmonella strains S15 and S639 were identified which belong to serotype Typhimurium and Thompson, respectively. We observed that both mcr-9 genes were located on conjugative IncHI2 plasmids which encoded numerous resistance genes, likely facilitating the dissemination of mcr-9 by co-resistance mechanisms. The mcr-9 cassettes encoded on the two plasmids were not identical: downstream of the mcr-9 genes, we found IS1 on one plasmid (pS15), while the other had a WbuC-IS26 (pS639). Despite the presence of mcr-9 cassettes, the strains were not rendered colistin resistant. Yet, it is of epidemiological importance to implement surveillance to be able to observe and possibly control the spread of mcr-9 due to its potential to mediate resistance to the last-resort antibiotic colistin.


Harman in alcoholic beverages: pharmacological and toxicological implications.
Harman, a beta-carboline compound, was identified and quantitated in beer and wine samples using a combination of high performance liquid chromatography with fluorescence detection and gas chromatography-negative chemical ionization mass spectrometry. The concentration of harman in beer (7.3-140.0 ng/ml) was greater than in wine (0.8-10.5 ng/ml) and was not related to alcohol content. The pharmacological and toxicological implications of harman in alcoholic beverages are discussed.


Best practices: that improved patient outcomes and agency operational performance.
OASIS gave Medicare-certified home care providers our first uniform external comparative data to quantify patient outcomes. PPS reimbursement offered further opportunity to use the data to measure operational performance. This article describes the use of external comparative data and PDSA methodology to identify best practices that improved patient outcomes and agency operational performance.


Differential effect of spermine on nuclear and cytoplasmic transfer RNA methyl transferases from Xenopus laevis Oocytes.
X laevis ovarian tissue or isolated oocytes contain two major tRNA methyl transferase activities capable of methylating total E. coli tRNA using S-adenosyl methionine as a methyl donor. These enzymes can be resolved by chromatography on DEAE-cellulose or by gel filtration on Sephadex G-200 into fractions I and II. The tRNA methyl transferase I which is present mainly in the oocyte nuclei, has a molecular weight of 190,000 and an apparent Km for S-adenosyl methionine of 1.5 microM. The activity of peak II which exists predominantly in the oocyte cytoplasm, has a molecular weight of 125,000 and an apparent Km for S-adenosyl methionine of 17 microM. The most striking difference between these two enzymes, however, resides in their response to spermine or magnesium ions. The nuclear enzyme is activated more that 8 fold by spermine and 4 fold by Mg2+ while the cytoplsmic activity is slightly inhibited by the polyamine and unaffected by Mg2+. The effect of spermine on the nuclear tRNA methyl transferase is highly dependent on the salt concentration since the stimulatory effect of the polyamine decrease at KCI concentrations above 100 mM becoming inhibitory above 200 mM. Spermine increases 4 fold the Vmax of the reaction catalyzed by the nuclear enzyme but does not affect its apparent Km for tRNA which is approximately 2.9 microM. The apparent Km for tRNA of the cytoplasmic enzyme is 3.3 microM.


The roles of place-value understanding and non-symbolic ratio processing system in symbolic rational number processing.
While it has been widely demonstrated that children's and adolescents' understanding of rational number plays an important role in their mathematics achievement, we have limited knowledge about the cognitive correlates of this understanding. The current study aimed at examining whether children's non-symbolic ratio processing and their understanding of place-value structure of whole numbers play a role in their understanding of fractions and decimals and whether their roles are different for fractions versus decimal understanding. A sample of 124 fourth graders was tested. Participants were tested on their symbolic rational number processing, non-symbolic ratio processing, place-value understanding of whole numbers, mathematics achievement, as well as a series of domain-general and domain-specific cognitive skills related to symbolic rational number processing. The findings suggest that, while the understanding of place value of whole numbers significantly predicted the understanding of both fractions and decimals, non-symbolic ratio processing specifically predicted the understanding of fractions, but not decimals. The findings highlight the roles of place-value understanding and non-symbolic ratio processing in the acquisition of symbolic rational numbers.


Algorithmic analysis of relational learning processes in instructional technology: Some implications for basic, translational, and applied research.
A few noteworthy exceptions notwithstanding, quantitative analyses of relational learning are most often simple descriptive measures of study outcomes. For example, studies of stimulus equivalence have made much progress using measures such as percentage consistent with equivalence relations, discrimination ratio, and response latency. Although procedures may have ad hoc variations, they remain fairly similar across studies. Comparison studies of training variables that lead to different outcomes are few. Yet to be developed are tools designed specifically for dynamic and/or parametric analyses of relational learning processes. This paper will focus on recent studies to develop (1) quality computer-based programmed instruction for supporting relational learning in children with autism spectrum disorders and intellectual disabilities and (2) formal algorithms that permit ongoing, dynamic assessment of learner performance and procedure changes to optimize instructional efficacy and efficiency. Because these algorithms have a strong basis in evidence and in theories of stimulus control, they may have utility also for basic and translational research. We present an overview of the research program, details of algorithm features, and summary results that illustrate their possible benefits. It also presents arguments that such algorithm development may encourage parametric research, help in integrating new research findings, and support in-depth quantitative analyses of stimulus control processes in relational learning. Such algorithms may also serve to model control of basic behavioral processes that is important to the design of effective programmed instruction for human learners with and without functional disabilities.


Hilbert Space in Isotopologue Dy(III) SMM Dimers: Dipole Interaction Limit in [163/164Dy2(tmhd)6(tape)]0 Complexes.
Single-molecule magnets are molecular complexes proposed to be useful for information storage and quantum information processing applications. In the quest for multilevel systems that can act as Qudits, two dysprosium-based isotopologues were synthesized and characterized. The isotopologues are [164Dy2(tmhd)6(tape)] (1(I=0)) and [163Dy2(tmhd)6(tape)] (2(I=5/2)), where tmhd = 2,2,6,6-tetramethylheptandionate and tape = 1,6,7,12-tetraazaperylene. Both complexes showed slow relaxation at a zero applied magnetic field with dominant Orbach and Raman relaxation mechanisms. μSQUID studies at milli-Kelvin temperatures reveal quasi-single ion loops, in contrast with the expected S-shape (near zero field) butterfly loops, characteristic of antiferromagnetically coupled dimeric complexes. Through analysis of the low-temperature data, we find that the interaction operating between Dy(III) is small, leading to a small exchange biasing from the zero-field transition. The resulting indirectly coupled nuclear states are degenerate or possess a small energy difference between them. We, therefore, conclude that for the creation of Qudits with enlarged Hilbert spaces, shorter Dy(III)···Dy(III) distances are deemed essential.


[Chemical constituents from ethyl acetate extract of flower of Albizia julibrissin].
The ethyl acetate extract of the flower of Albizia julibrissin was isolated and purified by silica gel, Sephadex LH-20 and MCI GEL CHP-20P column chromatography to yield 29 compounds. Their structures were elucidated as 8-hydroxy-2, 6-dimethyl-2E, 6Z-octadienoic acid (1), 8-O-formyl-2, 6-dimethyl-2E, 6Z-octadienoic acid (la), 8-hydroxy-2, 6-dimethyl-2E, 6E-octadienoic acid (2), 8-O-formyl-2, 6-dimethyl-2E, 6E-octadienoic acid (2a), (2E, 6S)-2, 6-dimethyl-6-O-beta-D-xylpyranosyloxy-2, 7-menthia-folic acid (3), clovan-2beta, 9alpha-diol (4), 2beta-O-formyl-clovan-9alpha-ol (4a), 2beta, 9alpha-O-diformyl-clovan (4b), vomifoliol (5), (6S, 9R)-roseoside (6), vanillin (7), 4-O-ethylgallic acid (8), 3-ethoxy4-hydroxy-benzoic acid (9), p-hydroxybenzaldehyde (10), gallic acid (11), protocatechoic acid (12), stearic acid (13), palmitic acid (14), 2, 3-dihydroxypropyl hexadecanoate (15), linoleic acid (16), scopoletin (17), indole-3-carboxaldehyde (18), 2-furoic acid (19), 5-(hydroxymethyl)-2-furaldehyde (20), (22E, 24R)-5alpha, 8alpha-epidioxy-ergosta-6, 22-dien-3beta-ol (21), (22E, 24R)-5alpha, 8alpha-epidioxy-ergosta-6, 9, 22-trien-3beta-ol (22), (+)-lariciresinol 9'-stearate (23), formononetin (24) and uridine (25). Compounds 1a, 2a, 4a and 4b were new artifacts from the separation process, and others were obtained from A. julibrissin for the first time.


Focal seizures versus epileptic spasms in children with focal cortical dysplasia and epilepsy onset in the first year.
Focal cortical dysplasia (FCD) has been recognized as one of the most frequent causes of drug resistant epilepsy, especially in children. In infancy, onset of FCD-related epilepsy is substantially characterized by epileptic spasms (ES) or focal seizures. Which elements pertaining to the FCD are responsible for the onset of one type of seizure over the other is still unclear. Purpose of our study was to compare the characteristics of FCDs in terms of lateralization and site in patients with epileptic spasms versus patients with focal seizures. We retrospectively reviewed data from 41 patients with FCD related epilepsy with onset during the first 14 months of life. Seizure semeiology and drug resistance were analyzed, as were age at onset and FCD site and lateralization. Twenty-one children had focal seizures, 11 had ES and nine had focal seizures followed by ES. Mean age at onset was respectively 8.2, 5.1 and 1.8 months. Drug resistance was present in respectively 38.5%, 34.6% and 26.9% of children. Among patients with only ES, 90.9% had an exclusively frontal FCD localization, versus 42.9% of patients with focal seizures and 11.1% of patients with focal seizures followed by ES. FCD lateralization was right sided respectively in 47.6%, 81.8% and 66.7% of patients. Frontal lobe localization of FCDs was closely associated with ES (p=0.001). Moreover we also found that patients with focal seizures followed by ES had a significantly earlier age at onset compared to patients with focal seizures only (p<0.001). The association between ES and right-sided FCD lateralization, even if numerically suggestive, did not reach statistical significance (p=0.16). There was no significant association between seizure type and drug resistance (p=0.08).


A pilot study of rat brain regional distribution of calcitonin, katacalcin and calcitonin gene-related peptide before and after antipsychotic treatment.
In contrast to extensive determinations of calcitonin gene-related peptide (CGRP) in neural tissues, calcitonin and its carboxyl-terminal flanking peptide katacalcin (in human PDN-21) have not been systematically measured by radioimmunoassay (RIA) in discrete brain structures. Using microwave irradiation (MW), a procedure that increases the recovery of neuropeptides, we investigated by radioimmunoassay (RIA) the rat brain regional distribution of CGRP like- immunoreactivity (-LI), calcitonin-LI, and katacalcin-LI. Calcitonin-LI and katacalcin-LI were found in low concentrations in frontal cortex, occipital cortex, striatum and hippocampus. Moreover, a 4-week treatment with antipsychotic drugs altered the concentrations of the calcitonin-gene family peptides in the frontal cortex, occipital cortex, and hippocampus; the magnitude of these changes, however, was only moderate. Lastly, calcitonin-LI and katacalcin-LI baseline concentrations as well as after antipsychotic treatment were highly correlated in the frontal cortex, striatum, and hippocampus. The possible regulatory role of calcitonin gene family peptides in the central nervous system (CNS) needs to be further explored.


Blood Trihalomethane Concentrations and Osteoarthritis among U.S. Population Aged over 50 Years.
Exposure to trihalomethanes (THMs) has been associated with inflammation and oxidative stress, which are implicated in osteoarthritis. However, the association of THM exposure with osteoarthritis is unknown. Therefore, we pooled seven independent National Health and Nutrition Examination Survey cycles (1999-2012) among participants aged over 50 years who had quantified blood concentrations of chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM). Among 4,077 adults aged over 50 years, 781 (21.3%) reported osteoarthritis. Logistic regression models showed increased odds of osteoarthritis across the categories of blood BDCM, DBCM, and brominated THM (Br-THM, which was the sum of BDCM, DBCM, and TBM) concentrations [odds ratios = 1.46 (95% CI 1.09-1.94), 1.53 (95% CI 1.15-2.04), and 1.35 (95% CI 0.97-1.88), respectively], comparing highest versus lowest exposure categories (quartiles or tertiles). Additionally, we found positive dose-response relationships between blood BDCM, DBCM, and Br-THM concentrations and serum markers of oxidative stress (i.e., gamma-glutamyltransferase). In summary, blood Br-THM concentrations were associated with elevated serum levels of gamma-glutamyltransferase as well as an increased risk of osteoarthritis among U.S. adults aged over 50 years. However, more prospective population studies are needed to verify these findings and explore the underlying mechanisms.


The adrenal cortico-medullary ratio in the fowl.
1. A new integrating method of assessing the proportions of cortical and medullary tissue in the avian adrenal gland is described and statistically evaluated. 2. It is shown that a single "central" section of the adrenal gland will suffice to obtain accurate results. 3. Each section was projected on to a grid of about 2500 intersection points and the ratio of points falling on cortical or medullary tissue was determined. 4. Applications of this method to normal fowls showed that there were significant breed, sex and, particularly, age differences in the cortico-medullary ratio of the fowl's adrenal glands.


Relationships of bovine leukemia virus prevalence in dairy herds and density of dairy cattle to human lymphocytic leukemia.
A case-control study was conducted to examine possible relationships between human acute lymphoid leukemia and exposure to dairy cattle and drinking of raw milk. Two hundred twenty-three persons with acute lymphoid leukemia, diagnosed during the years 1969 to 1971 and 1973 to 1980 from the 87 most rural Iowa counties, were accessed from case records at the Iowa State Health Registry for participation in the present study. Each person and 2 matched controls were interviewed for history of residence, exposure to dairy cattle, and consumption of nonpasteurized dairy products. Two types of comparisons between affected persons and controls were done: the prevalence of bovine leukemia virus infection (as measured by serologic study) in dairy herds with which the affected persons and controls had either occupational contact or from which they had consumed raw milk and the density of dairy cattle in the townships where affected persons and controls lived. The bovine leukemia virus infection prevalence in dairy herds with which affected persons had contact was 20%, whereas the infection prevalence in the herds with which the controls had contact was 38%. The density of dairy cows in townships where affected persons resided was generally less than that in townships where controls resided. However, there was one exception; the density of dairy cows at 20 years before diagnosis was higher (589) in townships where affected adult female persons resided, compared with that in townships where controls resided (567).


Phenotypical and molecular characterization of Acinetobacter spp. isolated from a pharmaceutical facility.
Characterizing microorganisms according to different criteria is useful when investigating sources of microbiological contamination in the pharmaceutical industry. The aim of this study was to characterize 38 Acinetobacter baumannii complex strains isolated from a biopharmaceutical industry by 16S rRNA sequencing, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS), multilocus sequence typing (MLST), antimicrobial susceptibility profile, biofilm formation, and sensibility to disinfectants. Thirty-three (86.9%) strains were identified by 16S rRNA gene sequencing as A. seifertii/pitti/nosocomialis/lactucae, four (10.5%) as A. baumannii, and one (2.6%) as A. vivianii/courvalini. MALDI-TOF/MS did not identify one strain, and incorrectly identified 30/37 (81.1%) strains as A. baumannii. Strains were assigned to 12 different STs, of which nine were newly defined in this study (STs 2091-2099). Twenty-six (68.4%) strains showed resistance to amikacin and gentamicin. Thirty-three (86.8%) strains were classified as moderately or strongly adherent on polystyrene. Alcohol 70%/15 min and quaternary ammonium 0.08%/20 min were not able to eliminate the biofilm formed, but sodium hypochlorite 0.1%/15 min was efficient. In conclusion, improved methods are needed to improve the identification of Acinetobacter strains in pharmaceutical industries. This organism is of particular concern as it forms recalcitrant biofilms, leading to persistence in the manufacturing environment and increased risk of product contamination.


Transcriptomic analysis of visceral adipose from healthy and diabetic obese subjects.
Understanding the role of visceral fat accumulation in the occurrence and progression of metabolic syndrome is of considerable interest. In order to understand the difference between visceral tissue biology of healthy and unhealthy obese individuals, we have used microarray profiling to compare genome-wide expression differences between visceral adipose tissue biopsies obtained from obese diabetics, and those from age and body mass index (BMI) matched normal glucose tolerance subjects. Whereas genes upregulated in diabetics showed enrichment of natural killer cell mediated cytotoxicity, the downregulated genes showed enrichment of biosynthesis of unsaturated fatty acids. Given the known inhibitory effect of unsaturated fatty acids on inflammation and natural killer cell number or activity, our results suggest that visceral inflammation resulting from decreased levels of unsaturated fatty acids may underlie progression of diabetes in obese individuals.


Atypical ADPKD Due to a DNAJB11 Pathogenic Variant: An Educational Case Report.
Due to next-generation sequencing, variants in new genes such as DNAJB11 are recently being identified as causing atypical autosomal dominant polycystic kidney disease (ADPKD). It is important to describe phenotypes associated with these variants in order to increase awareness among clinicians, especially since genetic variability affects ADPKD severity. We describe a 55-year-old female patient of Haitian origin who presented with slowly deteriorating kidney function, microscopic hematuria, proteinuria, enlarged kidneys with innumerable small cysts, and a family history of chronic kidney disease and cysts. The phenotype was atypical for ADPKD caused by PKD1 or PKD2 variants, since cysts were of small size, kidneys were only moderately enlarged, and the patient had no extra-renal involvement suggestive of typical ADPKD such as liver cysts, pancreatic cysts, cranial aneurysms, or cardiac abnormalities. A panel of genes was analyzed by next-generation massive sequencing techniques, including DNAJB11, DZIP1L, GANAB, HNF1B, PKD1, PKD2, and PKHD1. Genetic testing revealed a heterozygous variant in the DNAJB11 gene (c.123 dup), which is predicted to result in premature protein termination (p. Lys42*) and was classified by the laboratory as likely pathogenic. She was treated with candesartan 16 mg once daily to address her proteinuria. At the time of the most recent follow-up, her proteinuria has increased, and her kidney function continues to slowly deteriorate. DNAJB11 variants are a rare cause of atypical ADPKD. It is important to recognize the clinical features that help distinguish DNAJB11 from PKD1 and PKD2 variants. Atypical ADPKD due to DNAJB11 variants is usually characterized by small cysts, normal kidney size, proteinuria, progressive chronic kidney disease, and phenotypic overlap with autosomal dominant tubulointerstitial kidney disease (ADTKD). It may, however, present itself with enlarged kidneys as was seen in our patient. Genetic testing should be offered whenever a patient presents atypical features of ADPKD, which also requires increased awareness among clinicians regarding the various phenotypes of atypical ADPKD.


Dichlorobis(1-propylimidazolidine-2-thione-kappaS)cobalt(II).
The crystal structure of the title compound, [CoCl(2)(C(6)H(12)N(2)S)(2)], consists of monomer units of a Co(II) atom coordinated to two 1-propylimidazolidine-2-thione ligands and to two chloride ions. The heterocyclic thione ligand is monodentate and coordinated to the metal through the thione S atom. The environment around the Co(II) atom is a slightly distorted tetrahedron. The Co-S bond lengths are 2.341 (2) and 2.330 (2) A, and the Co-Cl bond lengths are 2.234 (2) and 2.238 (2) A. The most important point of distortion is the S-Co-S bond angle of only 97.83 (8) degrees. Intramolecular classical hydrogen bonds are found between the chloride ions and the N-H groups. Additionally, intra- and intermolecular non-classical hydrogen bonds are found.


A modified nonpulsatile flow system for the in vitro study of cardiac valve prostheses.
An in vitro system was constructed for measurements of resistance to forward flow by cardiac valve prostheses at a wide spectrum of flow rates. There was a close correlation between the known area of constriction (valvular orifice) and that calculated from the flow/pressure relationship using derivations of the Bernoulli equation. This simple setup appears particularly suited to determine hydrodynamic efficiency of various cardiac valve concepts on a comparative basis.


Fast switching from isotropic liquids to nematic liquid crystals: rotaxanes as smart fluids.
We examine a solution of rod-like piston-rotaxanes, which can switch their length by external excitation (for example optically) from a short state of length L to a long state of length qL. We show that this solution can exhibit a number of different behaviours. In particular it can rapidly switch from an isotropic to a nematic liquid crystalline state. There is a minimum ratio q* = 1.13 for which transitions from a pure isotropic state to a pure nematic state are possible. We present a phase-switching diagram, which gives the six possible behaviours for this system. It turns out that a large fraction of the phase switching diagram is occupied by the transition from a pure isotropic to a pure nematic state.


Metabolism of intact reticulocytes and mitochondria under lowered energy load induced by cycloheximide.
Cycloheximide was used to decrease the energy load by inhibitors of hemoglobin synthesis as the major ATP-consumer in intact rabbit reticulocytes. Inhibitor concentrations up to 2.5 X 10(-5) M led to decreased ATP-production at simultaneously elevated ATP/ADP ratios. Higher inhibitor levels resulted in further decreasing ATP-production but now in the reverse parallel to declining ATP/ADP ratios. Studies with intact reticulocyte mitochondria revealed almost no influence on respiration rates at the low range of concentrations but increasing inhibitions of state 3, state 4 and uncoupled respiration as well, with a 50% inhibition around 3 mM. Thus the dual action of the inhibitor is obviously due to the specific suppression of protein synthesis on the one hand and the unspecific inhibition of mitochondrial respiration on the other. Similar conclusions have been drawn by using ouabain to suppress the ATP-consumption by Na-K-ATPase. A preliminary load characteristic for rabbit reticulocytes with glucose as substrate is presented.


Transforming growth factor beta 1 and fibronectin messenger RNA in rat brain: responses to injury and cell-type localization.
Transforming growth factor-beta 1 rapidly increases in adult rat brain in response to experimental lesions. This study characterized the schedule of changes, regional distribution, and cellular localization of striatal transforming growth factor-beta 1 messenger RNA and fibronectin messenger RNA following partial striatal deafferentation by frontal cortex ablation. Frontal cortex ablation induced striatal transforming growth factor-beta 1 messenger RNA elevations that coincided temporally and overlapped anatomically with the course of degeneration of cortico-striatal afferent fibers. Within three days post-lesioning, transforming growth factor-beta 1 messenger RNA was localized at the cortical wound. By 10 days, the anatomical site of transforming growth factor-beta 1 messenger RNA expression shifted to the dorsal half of the deafferented striatum and co-localized with OX-42+ immunostained microglia-macrophage at the site of degenerating afferent terminals. Similarly, fibronectin messenger RNA also shifted from the cortical wound to the deafferented striatum by 10 days post-lesioning. Fibronectin messenger RNA was localized to glial fibrillary acidic protein+ immunostained astrocytes surrounding degenerating corticostriatal afferents. Infusion of transforming growth factor-beta 1 peptide elevated striatal and cortical fibronectin messenger RNA. These findings suggest that microglia-macrophage associated with degenerating afferent fibres can upregulate transforming growth factor-beta 1 messenger RNA and may influence fibronectin messenger RNA synthesis in reactive astrocytes. This study suggests that transforming growth factor-beta 1 has a role in controlling extracellular matrix synthesis following brain injury, which is analogous to that in peripheral wound healing.


Detection of a North American lineage H5 avian influenza virus in a South African wild duck.
An H5-coinfection of a sample from wild ducks from which an H3N8 virus was isolated in 2004 was detected by reverse transcription polymerase chain reaction (RT-PCR). Sequence analysis of the partial H5 gene revealed that the strain was of low pathogenicity according to the amino acid sequence PQRTGLF at the Ho cleavage site. Phylogenetic analysis demonstrated that the partial H5 gene sequence fell within the American H5 lineage and shared 99.6% nucleotide sequence identity with the A/mallard duck/ALB/57/1976 (H5N2) strain isolated in 1976. Interregional transmission of influenza virus genes has been reported occasionally, although this is the first report from South Africa, where other influenza viruses have always had Eurasian origins.


Barriers to Incident Reporting among Nurses: A Qualitative Systematic Review.
Incident reporting in health care prevents error recurrence, ultimately improving patient safety. A qualitative systematic review was conducted, aiming to identify barriers to incident reporting among nurses. Joanna Briggs Institute methodology for qualitative systematic reviews was followed, with data extracted using JBI QARI tools, and selected studies assessed for methodological quality using Critical Appraisal Skills Program (CASP). A meta-aggregation synthesis was carried out, and confidence in findings was assessed using GRADE ConQual. A total of 921 records were identified, but only five studies were included. The overall methodological quality of these studies was good and GRADE ConQual assessment score was "moderate." Fear of negative consequences was the most cited barrier to nursing incident reporting. Barriers also included inadequate incident reporting systems and lack of interdisciplinary and interdepartmental cooperation. Lack of nurses' necessary training made it more difficult to understand the importance of incident reporting and the definition of error. Lack of effective feedback and motivation and a pervasive blame culture were also identified.


Energy Level Matching and Band Edge Reconfiguration for Enhanced Charge Transport in Dion-Jacobson 3D/2D Perovskite Heterojunctions.
Generally, the 2D CsPbI3 layer capping on 3D counterparts has been considered as an effective strategy for both enhancing photovoltaic efficiency and stability. However, the intrinsically poor out-of-plane charge transport through the 2D layer remarkably hinders the overall performance of solar devices. To overcome such a challenge, we report the rationally designed 3D-CsPbI3/2D-(PYn)PbI4 (n = 1-4) heterojunctions with desirable energy level matching. It is evidenced that the valence band (VB) edge reconfiguration would occur with the increase of n, accompanied by the VB maximum (VBM) of the 2D component moving down from the higher level above that of the 3D component to the underneath. Consequently, the as-constructed 3D/2D-(PYn)PbI4 (n = 1, 2) heterojunctions exhibit optimal energy level matching, with accelerated transport of holes from 3D to 2D component and limited backflow of electrons. These findings might provide some meaningful insights on the energy level matching in 3D/2D perovskite heterojunctions.


Single-step PCR-based genetic sex determination of rat tissues and cells.
The advent of genome editing strategies has expanded the range of animal models available for gene manipulation and renewed research interest in the rat. Gender is a key variable for in vivo gene function analyses. Here, we present a simple PCR-based method to determine genetic sex in the rat.


Is quantitative magnetic resonance imaging valuable in the assessment of trabecular bone structure in osteoporosis?
This study aims to evaluate the value of quantitative magnetic resonance imaging in the assessment of bone trabeculae in osteoporosis by comparing the results with dual-energy X-ray (DXA) absorptiometry. The study consisted of 85 postmenopausal women (mean age 57.2 years; range 43 to 83 years) underwent both DXA absorptiometry and lumbar quantitative magnetic resonance imaging. T2 and T2* values were calculated by magnetic resonance imaging and the results were compared with bone mineral density. According to bone mineral density t-scores; there were 32 normal, 30 osteopenic, and 23 osteoporotic patients. T2 values of L1- L4 were different in normal with osteoporotic, and the osteopenic with osteoporotic groups. There were increased T2 values with reducing t-scores. Comparing the normal and osteopenic groups, no statistical difference was found in T2 measurements of lumbar vertebrae, except L4. T2* values of L1-L4 vertebrae were not statistically different between the study groups. T2 measurements of lumbar vertebra on quantitative magnetic resonance imaging may be useful in evaluation of bone trabeculae in osteoporosis, and may also be helpful in differentiation of osteoporotic from normal, and osteopenic from osteoporotic patients.


Suppression of the HPA Axis During Cholestasis Can Be Attributed to Hypothalamic Bile Acid Signaling.
Suppression of the hypothalamic-pituitary-adrenal (HPA) axis has been shown to occur during cholestatic liver injury. Furthermore, we have demonstrated that in a model of cholestasis, serum bile acids gain entry into the brain via a leaky blood brain barrier and that hypothalamic bile acid content is increased. Therefore, the aim of the current study was to determine the effects of bile acid signaling on the HPA axis. The data presented show that HPA axis suppression during cholestatic liver injury, specifically circulating corticosterone levels and hypothalamic corticotropin releasing hormone (CRH) expression, can be attenuated by administration of the bile acid sequestrant cholestyramine. Secondly, treatment of hypothalamic neurons with various bile acids suppressed CRH expression and secretion in vitro. However, in vivo HPA axis suppression was only evident after the central injection of the bile acids taurocholic acid or glycochenodeoxycholic acid but not the other bile acids studied. Furthermore, we demonstrate that taurocholic acid and glycochenodeoxycholic acid are exerting their effects on hypothalamic CRH expression after their uptake through the apical sodium-dependent bile acid transporter and subsequent activation of the glucocorticoid receptor. Taken together with previous studies, our data support the hypothesis that during cholestatic liver injury, bile acids gain entry into the brain, are transported into neurons through the apical sodium-dependent bile acid transporter and can activate the glucocorticoid receptor to suppress the HPA axis. These data also lend themselves to the broader hypothesis that bile acids may act as central modulators of hypothalamic peptides that may be altered during liver disease.


Tumor localization and beam monitoring--electrofluorotomography.
Methodology and instrumentation are presented which are potentially capable of presenting fluoroscopically derived transverse axial body sections for use in radiation-oncology treatment planning and beam monitoring. These combine the methods of Takahashi for generating transverse axial tomograms with electronic radiography, electrofluorotomography, and a contouring program for extracting body and tumor contours in a digital format. The system will also be capable of assuring both initial and day-to-day beam alignment.


Confronting the loss of trophic support.
Classic experiments with peripheral sympathetic neurons established an absolute dependence upon NGF for survival. A forgotten problem is how these neurons become resistant to deprivation of trophic factors. The question is whether and how neurons can survive in the absence of trophic support. However, the mechanism is not understood how neurons switch their phenotype to lose their dependence on trophic factors, such as NGF and BDNF. Here, we approach the problem by considering the requirements for trophic support of peripheral sympathetic neurons and hippocampal neurons from the central nervous system. We developed cellular assays to assess trophic factor dependency for sympathetic and hippocampal neurons and identified factors that rescue neurons in the absence of trophic support. They include enhanced expression of a subunit of the NGF receptor (Neurotrophin Receptor Homolog, NRH) in sympathetic neurons and an increase of the expression of the glucocorticoid receptor in hippocampal neurons. The results are significant since levels and activity of trophic factors are responsible for many neuropsychiatric conditions. Resistance of neurons to trophic factor deprivation may be relevant to the underlying basis of longevity, as well as an important element in preventing neurodegeneration.


Pt/CNT Micro-Nanorobots Driven by Glucose Catalytic Decomposition.
Swimming micro-nanorobots have attracted researchers' interest in potential medical applications on target therapy, biosensor, drug carrier, and others. At present, the experimental setting of the swimming micro-nanorobots was mainly studied in pure water or H2O2 solution. This paper presents a micro-nanorobot that applied glucose in human body fluid as driving fuel. Based on the catalytic properties of the anode and cathode materials of the glucose fuel cell, platinum (Pt) and carbon nanotube (CNT) were selected as the anode and cathode materials, respectively, for the micro-nanorobot. The innovative design adopted the method of template electrochemical and chemical vapor deposition to manufacture the Pt/CNT micro-nanorobot structure. Both the scanning electron microscope (SEM) and transmission electron microscope (TEM) were employed to observe the morphology of the sample, and its elements were analyzed by energy-dispersive X-ray spectroscopy (EDX). Through a large number of experiments in a glucose solution and according to Stoker's law of viscous force and Newton's second law, we calculated the driving force of the fabricated micro-nanorobot. It was concluded that the structure of the Pt/CNT micro-nanorobot satisfied the required characteristics of both biocompatibility and motion.


Clinical Proteomics for Post-Hematopoeitic Stem Cell Transplantation Outcomes.
Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy. The past decade has been characterized by an explosive evolution of proteomics technologies, largely due to important advances in high-throughput MS instruments and bioinformatics. Building on these opportunities, blood biomarkers have been identified and validated both as promising diagnostic tools, prognostic tools that risk-stratify patients before future occurrence of GVHD and as predictive tools for responsiveness to GVHD therapy and non-relapse mortality. These biomarkers might facilitate timely and selective therapeutic intervention. This review summarizes current information on clinical proteomics for GVHD as well as other complications following HSCT. Finally, it proposes future directions for the translation of clinical proteomics to discovery of new potential therapeutic targets to the development of drugs.


ARE POPULATIONS ISLANDS? ANALYSIS OF CHLOROPLAST DNA VARIATION IN AQUILEGIA.
The degree to which conspecific populations are interconnected via ongoing gene flow remains an important focus of evolutionary biology. One major difficulty in distinguishing ongoing gene flow from historical subdivision is that either process can generate similar estimates of apparent gene flow. Thus, gene flow estimates themselves are insufficient to distinguish between these alternatives. However, genetic data coupled with additional information about demography and distribution do allow a distinction to be made. Here we address the specific question, does gene flow link populations of Aquilegia? In a survey of a 525 B.P. chloroplast DNA fragment sampled from 251 individual plants from 18 populations of three taxa, five haplotypes were identified. No significant relationship between geographic distance and apparent gene flow between population pairs existed. Further, the estimated level of gene flow was entirely compatible with a historical subdivision of Aquilegia populations during the late Pleistocene or early Holocene. Therefore, these patterns of variation are due not to ongoing gene flow, but rather to historical association among populations. Thus Aquilegia populations may be considered as distinct evolutionary entities with regard to seed-mediated processes. As a result, comparative analysis of ecological traits undergoing potentially rapid evolution (e.g., life histories, mating systems, inbreeding depression) should be possible in these taxa.


[The development of a computerized acidimeter].
A instrument combining advanced computer technology with tradition acidimeter in order to overcome the inconvenience of operating and the subjectivity of result is introduced. The instrument realizes, automatic adjust of Standard and automatic complement of temperature and improve the precision to 0.01 grade. It has a good performance.


The contribution of stem cells to epidermal and hair follicle tumours in the dog.
Although cutaneous stem cells have been implicated in skin tumourigenesis in humans, no studies have been conducted to elucidate the presence and the possible role of stem cells in hair follicle tumours in the dog. Stem cell markers are expressed in canine epidermal and follicular tumours and can be used to better understand the biology and origin of these tumours. In the present study, normal skin sections and 44 follicular tumours were retrospectively investigated for the immunohistochemical expression of keratin 15 (K15) and nestin. In addition, 30 squamous cell carcinomas were evaluated for K15 expression. In normal skin, K15 and nestin were expressed in the outer root sheath cells of the isthmic portion of the hair follicle (bulge region), and K15 expression was also scattered in the basal cell layer of the epidermis. Infundibular keratinizing acanthomas, pilomatricomas and squamous cell carcinomas were mostly negative for K15, trichoblastomas were moderately to strongly positive, tricholemmomas were either negative or strongly positive, and trichoepitheliomas had heterogeneous staining. Nestin expression was generally faint in all follicular tumours. Our results show that K15 can be a reliable marker for investigating the role of stem cells in hair follicle tumours of the dog, while nestin was judged to be a nonoptimal marker. Furthermore, our study suggests that hair follicle stem cells are present in the bulge region of hair follicles and could possibly play a role in tumourigenesis of canine tumours originating from this portion of the follicle, namely trichoblastomas, tricholemmomas and trichoepitheliomas. The loss of K15 expression in squamous cell carcinomas compared with normal skin suggests that this event could be important in the malignant transformation.


Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction and Natural Heart Regeneration in Newborn Piglets.
Newborn mammals, including piglets, exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). The electrophysiologic properties of this naturally regenerated myocardium have not been examined. We hypothesized that epicardial conduction is preserved after P1 MI in piglets. Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation at age P1 (n = 6) or P7 (n = 7), After 7 weeks, cardiac magnetic resonance imaging was performed with late gadolinium enhancement for analysis of fibrosis. Epicardial conduction mapping was performed using custom 3D-printed high-resolution mapping arrays. Age- and weight-matched healthy pigs served as controls (n = 6). At the study endpoint, left ventricular (LV) ejection fraction was similar for controls and P1 pigs (46.4 ± 3.0% vs. 40.3 ± 4.9%, p = 0.132), but significantly depressed for P7 pigs (30.2 ± 6.6%, p < 0.001 vs. control). The percentage of LV myocardial volume consisting of fibrotic scar was 1.0 ± 0.4% in controls, 9.9 ± 4.4% in P1 pigs (p = 0.002 vs. control), and 17.3 ± 4.6% in P7 pigs (p < 0.001 vs. control, p = 0.007 vs. P1). Isochrone activation maps and apex activation time were similar between controls and P1 pigs (9.4 ± 1.6 vs. 7.8 ± 0.9 ms, p = 0.649), but significantly prolonged in P7 pigs (21.3 ± 5.1 ms, p < 0.001 vs. control, p < 0.001 vs. P1). Conduction velocity was similar between controls and P1 pigs (1.0 ± 0.2 vs. 1.1 ± 0.4 mm/ms, p = 0.852), but slower in P7 pigs (0.7 ± 0.2 mm/ms, p = 0.129 vs. control, p = 0.052 vs. P1). Overall, our data suggest that epicardial conduction dynamics are conserved in the setting of natural heart regeneration in piglets after P1 MI.


Nucleic acid aptamers for clinical diagnosis: cell detection and molecular imaging.
Nucleic acid aptamers have recently attracted significant attention in the field of clinical diagnosis because they have numerous merits, such as high affinity, high specificity, small size, little immunogenicity, stable structures, and ease of synthesis. This review focuses on discussing the potential applications of aptamers in cell detection and molecular imaging. For the ex vivo cell detection, this review discusses the status of five strategies: endogenous nucleic acid analysis, flow cytometry analysis, nanoparticle-based cell sensing, microfluidic cell separation, and histological examination. This review also discusses in vivo molecular and cell imaging by introducing aptamer-based molecular imaging, cell imaging, and integrated imaging and therapy. On the basis of the status of these promising studies, this review summarizes several challenging issues and unmet needs that may require more effort or attention in the future.


Regulation of DNA superhelicity by rpoB mutations that suppress defective Rho-mediated transcription termination in Escherichia coli.
The highly defective rho-15 mutant of Escherichia coli produces plasmid DNA that is 22% less negatively supercoiled than DNA from an isogenic wild-type strain (J. S. Fassler, G. F. Arnold, and I. Tessman, Mol. Gen. Genet. 204:424-429, 1986). We extended our measurements of plasmid superhelicity to additional rho mutants and to strains containing mutations that suppress rho transcription termination defects; the suppressor mutations were in the rpoB and the rho genes. The superhelicity of plasmid DNA was reduced by 11 and 10%, respectively, in the rho-702 and rho-201 mutants, both of which are less defective in Rho-mediated transcription termination than rho-15. Plasmid superhelicity was restored in all the suppressed rho mutants; in one rpoB mutant, plasmid DNA was even more negatively supercoiled than in rpoB+ cells, whether in a rho+ or rho mutant background. Suppression of rho mutants enabled them to maintain plasmids that could not be maintained in the mutants in the absence of the suppressor mutations. The results indicate that in addition to DNA gyrase, topoisomerase I, and Rho, RNA polymerase is also a determinant of DNA superhelicity, and its effect is modified by the Rho protein. We propose that Rho may increase the degree of DNA unwinding by the transcription complex, possibly at transcription termination sites.


Impact of microaxillar mechanical left ventricular support on renal resistive index in patients with cardiogenic shock after myocardial infarction: a pilot trial to predict renal organ dysfunction in cardiogenic shock.
To evaluate the effects of left ventricular support with the microaxial left ventricular pump using the Impella device on the renal resistive index assessed by Doppler ultrasonography in haemodynamically stable patients with cardiogenic shock following myocardial infarction. A non-randomised interventional single-centre study. Consecutive patients with cardiogenic shock supported with an Impella were included during May 2018 and October 2018. The renal resistive index determined as a quotient of (peak systolic velocity - end diastolic velocity)/ peak systolic velocity was obtained using Doppler ultrasound; invasive blood pressure was determined in radial artery simultaneously for safety reasons. A total of 15 patients were measured. The renal resistive index was determined in both kidneys in 13 patients and for one kidney in two patients, respectively. The mean difference between right and left renal resistive index was 0.026 ± 0.023 (P=0.72). When increasing the Impella microaxillar mechanical support by a mean of 0.44 L/min (±0.2 L/min), the renal resistive index decreased significantly from 0.66 ± 0.08 to 0.62 ± 0.06 (P<0.001) consistently in all patients, whereas systolic or diastolic blood pressure remained unchanged. Microaxillar mechanical support by the Impella device in haemodynamically stable patients with cardiogenic shock led to a significant reduction of the renal resistive index without affecting systolic or diastolic blood pressure. This observation is consistent with the notion that Impella support may promote renal organ protection by enhancing renal perfusion.


MicroRNA 648 Targets ET-1 mRNA and is cotranscriptionally regulated with MICAL3 by PAX5.
Pulmonary hypertension (PHT) is associated with high mortality in sickle cell anemia (SCA). Previously, we showed that elevated levels of placenta growth factor (PlGF) in SCA patients correlate with increased levels of the potent vasoconstrictor endothelin-1 (ET-1) and PHT. Moreover, PlGF induced the expression of ET-1 via hypoxia-inducible factor 1α. Here, we show a novel example of ET-1 posttranscriptional regulation by PlGF via action of microRNA 648 (miR-648), which is subject to transcriptional coregulation with its host gene, MICAL3 (microtubule-associated monooxygenase, calponin, and LIM domain containing 3gene). PlGF repressed expression of miR-648 in endothelial cells. Luciferase reporter assays using wild-type and mutant ET-1 3' untranslated region (UTR) constructs, and transfection of miR-648 mimics showed that miR-648 targets the 3' UTR of ET-1 mRNA. Since miR-648 is located in a 5'-proximal intron of MICAL3, we examined which of three potential promoters was responsible for its expression. The MICAL3 distal promoter (P1) was the predominant promoter used for transcription of pre-miR-648, and it was under positive control by PAX5 (paired box protein 5) transcription factor, as demonstrated by the loss and gain of function of PAX5 activity, and chromatin immunoprecipitation analysis. These studies provide a novel link wherein PlGF-mediated downregulation of PAX5 attenuates miR-648 expression leading to increased ET-1 levels that are known to induce PHT in SCA.


Hypertension in HIV-1-infected patients and its impact on renal and cardiovascular integrity.
With increasing life spans of HIV-infected individuals under highly active antiretroviral therapy, long-term consequences of the chronic infection and antiretroviral treatment are becoming more prevalent. Data on prevalence and consequences of hypertension are limited, but recent studies suggest that HIV-infected individuals are at a higher risk of developing hypertension. In this prospective study, HIV-1-infected patients from the Frankfurt AIDS Cohort Study (FACS) were followed for 1 year to determine the frequency of systemic hypertension and to assess the associated clinical and demographic factors. A total 214 HIV-1-infected patients, predominantly Caucasian males, participated in the study. Prevalence of systemic hypertension was 29%. The groups of hypertensive and normotensive individuals were comparable in terms of ethnic background and duration of infection. As in the general population, hypertensive subjects were older (49.1+/-11.1 vs 39.0+/-8.1 years; P<0.0001) and waist-to-hip ratio was higher than in normotensive individuals (0.99+/-0.07 vs 0.93+/-0.08; P<0.0001). Hypertension was associated with a much higher frequency of persistent proteinuria (41.1% vs 2.8%; P<0.001), coronary heart disease (16.1% vs 1.3%; P<0.0001) and myocardial infarction (8.1% vs 0.7%; P<0.005), whereas most cardiovascular risk factors were similar in both groups. Our data do not demonstrate any association between the presence of hypertension and antiretroviral therapy or immune status. However, hypertension seems to have a high impact on the existing risk for premature cardiovascular disease. Furthermore, overt proteinuria is frequent in HIV-1 infection with hypertension and might be due to hypertensive nephrosclerosis as well as yet undefined renal disease in these patients.


Genome-wide single-nucleotide polymorphism data reveal cryptic species within cryptic freshwater snail species-The case of the Ancylus fluviatilis species complex.
DNA barcoding utilizes short standardized DNA sequences to identify species and is increasingly used in biodiversity assessments. The technique has unveiled an unforeseeably high number of morphologically cryptic species. However, if speciation has occurred relatively recently and rapidly, the use of single gene markers, and especially the exclusive use of mitochondrial markers, will presumably fail in delimitating species. Therefore, the true number of biological species might be even higher. One mechanism that can result in rapid speciation is hybridization of different species in combination with polyploidization, that is, allopolyploid speciation. In this study, we analyzed the population genetic structure of the polyploid freshwater snail Ancylus fluviatilis, for which allopolyploidization was postulated as a speciation mechanism. DNA barcoding has already revealed four cryptic species within A. fluviatilis (i.e., A. fluviatilis s. str., Ancylus sp. A-C), but early allozyme data even hint at the presence of additional cryptic lineages in Central Europe. We combined COI sequencing with high-resolution genome-wide SNP data (ddRAD data) to analyze the genetic structure of A. fluviatilis populations in a Central German low mountain range (Sauerland). The ddRAD data results indicate the presence of three cryptic species within A. fluviatilis s. str. occurring in sympatry and even syntopy, whereas mitochondrial sequence data only support the existence of one species, with shared haplotypes between species. Our study hence points to the limitations of DNA barcoding when dealing with organismal groups where speciation is assumed to have occurred rapidly, for example, through the process of allopolyploidization. We therefore emphasize that single marker DNA barcoding can underestimate the true species diversity and argue in strong favor of using genome-wide data for species delimitation in such groups.


Does a pre-hospital emergency pathway improve early diagnosis and referral in suspected stroke patients?--Study protocol of a cluster randomised trial [ISRCTN41456865].
Early interventions proved to be able to improve prognosis in acute stroke patients. Prompt identification of symptoms, organised timely and efficient transportation towards appropriate facilities, become essential part of effective treatment. The implementation of an evidence based pre-hospital stroke care pathway may be a method for achieving the organizational standards required to grant appropriate care. We performed a systematic search for studies evaluating the effect of pre-hospital and emergency interventions for suspected stroke patients and we found that there seems to be only a few studies on the emergency field and none about implementation of clinical pathways. We will test the hypothesis that the adoption of emergency clinical pathway improves early diagnosis and referral in suspected stroke patients. We designed a cluster randomised controlled trial (C-RCT), the most powerful study design to assess the impact of complex interventions. The study was registered in the Current Controlled Trials Register: ISRCTN41456865--implementation of pre-hospital emergency pathway for stroke--a cluster randomised trial. Two-arm cluster-randomised trial (C-RCT). 16 emergency services and 14 emergency rooms were randomised either to arm 1 (comprising a training module and administration of the guideline), or to arm 2 (no intervention, current practice). Arm 1 participants (152 physicians, 280 nurses, 50 drivers) attended an interactive two sessions course with continuous medical education CME credits on the contents of the clinical pathway. We estimated that around 750 patients will be met by the services in the 6 months of observation. This duration allows recruiting a sample of patients sufficient to observe a 30% improvement in the proportion of appropriate diagnoses. Data collection will be performed using current information systems. Process outcomes will be measured at the cluster level six months after the intervention. We will assess the guideline recommendations for emergency and pre-hospital stroke management relative to: 1) promptness of interventions for hyperacute ischaemic stroke; 2) promptness of interventions for hyperacute haemorrhagic stroke 3) appropriate diagnosis. Outcomes will be expressed as proportions of patients with a positive CT for ischaemic stroke and symptoms onset < or = 6 hour admitted to the stroke unit. The fields in which this trial will play are usually neglected by randomised controlled trial (RCT). We have chosen the cluster-randomised controlled trial (C-RCT) to address the issues of contamination, adherence to real practice, and community dimension of the intervention, with a complex definition of clusters and an extensive use of routine data to collect the outcomes.


Nanostructural Properties and Twist Periodicity of Cellulose Nanofibrils with Variable Charge Density.
Cellulose nanofibrils (CNFs) are a renewable and facile to produce nanomaterial that recently gained a lot of attention in soft material research. The nanostructural properties of the fibrils largely determine their self-organizing functionalities, and the ability to tune the CNF nanostructure through control of the processing parameters is therefore crucial for developing new applications. In this study, we systematically altered the CNF production parameters (i.e., variation in cellulose source, chemical, and mechanical treatment) to observe their impact on the nanostructural properties of the resulting fibrils. Atomic force microscopy (AFM) allowed detailed topological examination of individual CNFs to elucidate fibril properties such as contour length, kink distribution and the right-handed twist periodicity of individual fibrils. Statistical analysis revealed a large dependency of the fibril properties on the industrial treatment of the cellulose source material. Our results furthermore confirm that the average charge density of the fibrils regulates both contour length and twist periodicity and, thus, has a very strong impact on the final morphology of CNFs. These results provide a route to tune the detailed nanostructure of CNFs with potential impact on the self-organization of these biological colloids and their optimal use in new nanomaterials.


Differential roles of the dorsal and ventral hippocampus in predator odor contextual fear conditioning.
The study of fear memory is important for understanding various anxiety disorders in which patients experience persistent recollections of traumatic events. These memories often involve associations of contextual cues with aversive events; consequently, Pavlovian classical conditioning is commonly used to study contextual fear learning. The use of predator odor as a fearful stimulus in contextual fear conditioning has become increasingly important as an animal model of anxiety disorders. Innate fear responses to predator odors are well characterized and reliable; however, attempts to use these odors as unconditioned stimuli in fear conditioning paradigms have proven inconsistent. Here we characterize a contextual fear conditioning paradigm using coyote urine as the unconditioned stimulus. We found that contextual conditioning induced by exposure to coyote urine produces long-term freezing, a stereotypic response to fear observed in mice. This paradigm is context-specific and parallels shock-induced contextual conditioning in that it is responsive to extinction training and manipulations of predator odor intensity. Region-specific lesions of the dorsal and ventral hippocampus indicate that both areas are independently required for the long-term expression of learned fear. These results in conjunction with c-fos immunostaining data suggest that while both the dorsal and ventral hippocampus are required for forming a contextual representation, the ventral region also modulates defensive behaviors associated with predators. This study provides information about the individual contributions of the dorsal and ventral hippocampus to ethologically relevant fear learning.


Role of platelets as mediators that link inflammation and thrombosis in atherosclerosis.
Platelets, crucial mediators of the acute complications of atherosclerosis that cause life-threatening ischemic events at late stages of the disease, are also key effectors of inflammation throughout plaque development through their interaction with endothelial and immune cells in the injured vessel wall. During the first steps of atherosclerosis, blood inflammatory leukocytes interact with the damaged endothelium in areas rich in platelet aggregates. In late stages of the disease, platelets secrete several inflammatory molecules, even without forming aggregates. These molecules exacerbate the inflammation and induce the transition from chronic to acute disease, featuring increased instability of the atherosclerotic lesion that results in plaque rupture and thrombosis. Moreover, platelets play an important role in vascular wall remodeling induced by chronic inflammation by controlling vascular cell differentiation and proliferation. In this review, we discuss the role of platelets as cell mediators that link inflammation and thrombosis in atherosclerotic disease and their potential in the development of new therapeutic tools to fight cardiovascular disease.


Plant water status, ethylene evolution, N(2)-fixing efficiency, antioxidant activity and lipid peroxidation in Cicer arietinum L. nodules as affected by short-term salinization and desalinization.
Salinity induced changes in ethylene evolution, antioxidant defense system, N(2)-fixing efficiency and membrane integrity in relation to water and mineral status in chickpea (Cicer arietinum L.) nodules were studied under screen house conditions. At vegetative stage (55-65 DAS) plants were exposed to single saline irrigation (Cl(-) dominated) of levels 0, 2.5, 5.0 and 10.0dSm(-1) and sampled after 3d. The other set of treated plants was desalinized by flooding and the plants were sampled after further 3d. Water potential (Psiw) of leaf and osmotic potential (Psis) of leaf and nodules significantly decreased from -0.44 to -0.56MPa and from -0.65 to -1.15MPa and from -0.75 to -1.77MPa, respectively upon salinization. RWC of leaf and nodules also reduced from 86.05% to 73.30% and 94.70% to 89.98%, respectively. The decline in Psis of nodules was due to accumulation of proline and total soluble sugar. In comparison to control, the increase in ethylene (C(2)H(4)) production was 35-108% higher and correspondingly increase in 1-aminocycloprane-1-carboxylic acid (ACC) content (37-126%) and ACC oxidase activity (31-118%) was also noticed. Similarly, marked increase in H(2)O(2) (25-139%) and thiobarbituric acid substances (TBRAS, 11-133%) contents was seen. N(2)-fixing efficiency i.e. N(2)-ase activity, leghemoglobin and N contents of nodules declined significantly after saline irrigation. The induction in specific activity of antioxidant enzymes was confirmed by the increase in activity of superoxide dismutase, peroxidase, ascorbate peroxidase, glutathione reductase and glutathione transferase, whereas reverse was true for catalase. These activated enzymes could not overcome the accumulation of H(2)O(2) in nodules. Ascorbic acid content also declined from 20 to 38%, whereas Na(+)/K(+) ratio and Cl(-) content were significantly enhanced. Upon desalinization, a partial recovery in all above metabolic processes and water relations parameters was noticed. It is suggested that ethylene in relation to water status and lipid peroxidation and along with other metabolic processes has an important role in induced nodules senescence under salinity.


Label-free impedance detection of cancer cells.
Ovarian cancer cells, SKOV3, have been immobilized onto platinum microelectrodes using anti-EPCAM capture antibodies and detected with high sensitivity using electrochemical impedance. The change in impedance following cell capture is strongly dependent on the supporting electrolyte concentration. By controlling the concentration of Dulbecco's phosphate buffered saline (DPBS) electrolyte, the double layer thickness can be manipulated so that the interfacial electric field interacts with the bound cells, rather than simply decaying across the antibody capture layer. Significantly, the impedance changes markedly upon cell capture over the frequency range from 3 Hz to 90 kHz. For example, using an alternating-current (ac) amplitude of 25 mV, a frequency of 81.3 kHz, and an open circuit potential (OCP) as the direct-current (dc) voltage, a detection limit of 4 captured cells was achieved. Assuming an average cell radius of 5 μm, the linear dynamic range is from 4 captured cells to 650 ± 2 captured cells, which is approximately equivalent to fractional coverages from 0.1% to 29%. An equivalent circuit that models the impedance response of the cell capture is discussed.


Studies on the site of phosphorylation of Ca2+/calmodulin-dependent protein kinase (CaM-kinase) IV by CaM-kinase kinase.
The phosphorylation site(s) involved in the activation of CaM-kinase IV by CaM-kinase kinase alpha was studied using a mutant CaM-kinase IV (K71R) in which Lys71 (ATP-binding site) was replaced with Arg, because the autophosphorylation of CaM-kinase IV occurring at multiple sites made it difficult to study phosphorylation of the enzyme by CaM-kinase kinase. Sequence analysis of the phosphopeptide from the trypsin digest of CaM-kinase IV (K71R) phosphorylated by CaM-kinase kinase alpha suggested that the phosphorylation of CaM-kinase IV by CaM-kinase kinase only occurred at Thr196. The recombinant mutant CaM-kinase IV in which Thr196 or Thr200 was replaced with nonphosphorylatable alanine showed little activity in the presence and absence of the kinase kinase. The mutant enzyme in which Thr196 was replaced with negatively charged aspartic acid showed almost 25 times as high activity as the wild-type enzyme in the absence of the kinase kinase, and no more activation was observed in its presence. In contrast, the enzyme in which Thr200 was replaced with aspartic acid showed little enzyme activity. Thus, it may be concluded that the phosphorylation of Thr196 in CaM-kinase IV by CaM-kinase kinase is necessary for the subsequent autophosphorylation and activation of CaM-kinase IV.


Detection of early proteomic alterations in 5xFAD Alzheimer's disease neonatal mouse model via MALDI-MSI.
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder, characterized by memory deficit and dementia. AD is considered a multifactorial disorder where multiple processes like amyloid-beta and tau accumulation, axonal degeneration, synaptic plasticity, and autophagic processes plays an important role. In this study, the spatial proteomic differences in the neonatal 5xFAD brain tissue were investigated using MALDI-MSI coupled to LC-MS/MS, and the statistically significantly altered proteins were associated with AD. Thirty-five differentially expressed proteins (DEPs) between the brain tissues of neonatal 5xFAD and their littermate mice were detected via MALDI-MSI technique. Among the 35 proteins identified, 26 of them were directly associated with AD. Our results indicated a remarkable resemblance in the protein expression profiles of neonatal 5xFAD brain when compared to AD patient specimens or AD mouse models. These findings showed that the molecular alterations in the AD brain existed even at birth and that some proteins are neurodegenerative presages in neonatal AD brain. HIGHLIGHTS: Spatial proteomic alterations in the 5xFAD mouse brain compared to the littermate. 26 out of 35 differentially expressed proteins associated with Alzheimer's disease (AD). Molecular alterations and neurodegenerative presages in neonatal AD brain. Alterations in the synaptic function an early and common neurobiological thread.


Exact relaxation dynamics in the totally asymmetric simple exclusion process.
The relaxation dynamics of the one-dimensional totally asymmetric simple exclusion process on a ring is considered in the case of step initial condition. Analyzing the time evolution of the local particle densities and currents by the Bethe ansatz method, we examine their full relaxation dynamics. As a result, we observe peculiar behaviors, such as the emergence of a ripple in the density profile and the existence of the excessive particle currents. Moreover, by making a finite-size scaling analysis of the asymptotic amplitudes of the local densities and currents, we find the scaling exponents with respect to the total number of sites to be -3/2 and -1, respectively.


Benefits of the Use of Sewage Sludge over EDTA to Remediate Soils Polluted with Heavy Metals.
Sewage sludges from urban wastewater treatment plants are often used to remediate degraded soils. However, the benefits of their use in metal-polluted soils remain unclear and need to be assessed in terms of factors besides soil fertility. This study examines the use of thermal-dried sewage sludge (TDS) as an amendment for heavy metal-polluted soil in terms of its effects on soil chemical properties, leachate composition, and the growth of native plant communities. To assess the response of the soil and its plant community to an increase in metal mobilization, the effects of TDS amendment were compared with those of the addition of a chelating agent (ethylenediaminetetraacetic acid [EDTA]). The experimental design was based on a real-case scenario in which soils from of an abandoned mine site were used in a greenhouse bioassay. Two doses of TDS and EDTA were applied to a soil containing high Pb, Zn, Cu, and Cd levels (4925, 5675, 404, and 25 mg kg, respectively). Soil pH was 6.4, and its organic matter content was 5.53%. The factors examined after soil amendment were soil fertility and heavy metal contents, leachate element losses, the plant community arising from the seed bank (plant cover, species richness and biodiversity, above/below ground biomass), and phytotoxic effects (chemical contents of abundant species). Thermal-dried sewage sludge emerged as a good phytostabilizer of Pb, Zn, Cu, and Cd given its capacity to reduce the plant uptake of metals and achieve rapid plant cover. This amendment also enhanced the retention of other elements in the plant root system and overall showed a better capacity to remediate soils polluted with several heavy metals. The addition of EDTA led to plant productivity losses and nutritional imbalances because it increased the mobility of several elements in the soil and its leachates.


Lymphoid markers, activation markers, and adhesion molecules in cutaneous biopsy specimens from HIV+ patients with disease progression. The Military Medical Consortium for the Advancement of Retroviral Research.
One important factor in understanding the pathogenesis of human immune deficiency virus (HIV) disease is documenting the patterns of immune dysregulation present in HIV-positive patients. The cells which home to skin are mainly certain subsets of T cells and, as opposed to the peripheral blood, where circulating factors may inhibit terminal phenotypic differentiation, the cutaneous environment potentiates differentiation during cutaneous eruptions. The authors' aim was to characterize the inflammatory dermatoses in biopsy specimens from HIV-positive patients with immunohistochemical stains for lymphoid markers, activation markers, and adhesion molecules and to determine if there was any correlation with the type of dermatosis and the HIV-disease stage. Lymphoid and activation markers as well as adhesion molecules were studied on cutaneous biopsy specimens from 96 inflammatory dermatoses in HIV-positive patients. The dermatoses included psoriasiform dermatoses with and without a lichenoid component, perivascular lymphoid dermatoses, perivascular and periadnexal inflammatory dermatoses, spongiotic dermatoses, granulomatous dermatoses, and neutrophilic dermatoses with and without vasculitis. Although there was a decrease in CD4/CD8 ratios in the cutaneous inflammatory dermatoses with progression of the disease, the ratios of CD4/CD8 cells were far higher than those in the peripheral blood. There were also increasing numbers of CD23+ cells and increased E-Selectin expression on endothelial cells from the early stages of disease, with no consistent pattern of ICAM-1 expression on epithelial cells with disease progression. The expression of lymphoid markers, activation markers, and adhesion molecules in the skin with progression of HIV disease, is consistent with a T helper (Th)1 to Th0/Th2 cytokine pattern of immune dysregulation. This cytokine pattern may be modified by the cytopathic effects of HIV on lymphoid and dendritic populations and by effects of other concurrent infections. Significant numbers of CD4+ T cells in skin infiltrates, with low peripheral CD4 T-cell counts, suggest that the cutaneous T-cell populations may be distinctive.


DISPERSION OF A NEW CORONAVIRUS SARS-COV-2 BY AIRLINES IN 2020: TEMPORAL ESTIMATES OF THE OUTBREAK IN MEXICO.
On January 23, 2020, China imposed a quarantine on the city of Wuhan to contain the SARS-CoV-2 outbreak. Regardless of this measure, the new infection has spread to several countries around the world. We developed a method to study the dissemination of this infection by airline routes and provide estimations of the time of arrival of the outbreak to different cities. Using the Kermack and McKendrick model complemented with diffusion on a graph composed of nodes and edges, we made an analysis of COVID-19 dispersion to other cities by air travel. The estimation was accurate in that it was possible to predict in the middle of February 2020 the arrival of the first outbreak in Mexico, which eventually occurred between March 20 and 30. This estimation was robust with respect to small changes in epidemiological parameters at the other nodes. The estimation of the time of arrival of the outbreak from its epicenter, allows for a time period to implement and strengthen preventive measures aimed at the general population as well as to strengthen hospital infrastructure and training of human resources. In the present study, this estimation was accurate, as observed from the real data of the beginning of the outbreak in Mexico City up to April 6, 2020.


Case Report: Kinetics and durability of humoral and cellular response of SARS-CoV-2 messenger RNA vaccine in a lung and kidney transplant recipient.
We present a case report of a 63-year-old female health care worker who is 15 years status post double lung transplant and six years status post living related donor kidney transplant who is healthy on a chronic immunosuppression regimen including prednisone, mycophenolate, and tacrolimus who received the SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech BNT162b2) primary series and had poor initial humoral response to the COVID-19 mRNA vaccine, then demonstrated a robust, sustained immune response against S1 and S2 antigens for over seven months after receiving the recommended vaccine doses, including booster dose, without developing COVID-19 or other serious adverse events. Her immune response to vaccination indicates effective formation of anti-spike T cell memory despite chronic immunosuppression. This case report provides a comprehensive characterization of her immune response to this SARS-CoV-2 vaccination series. As vaccine effectiveness data is updated, and as better understanding of immune response including hybrid immunity emerges, these findings may reassure that recipients of SOTs may be capable of durable immune responses to emerging variants of SARS-CoV-2.


Structural Elucidation of cis/trans Dicaffeoylquinic Acid Photoisomerization Using Ion Mobility Spectrometry-Mass Spectrometry.
Due to the recently uncovered health benefits and anti-HIV activities of dicaffeoylquinic acids (diCQAs), understanding their structures and functions is of great interest for drug discovery efforts. DiCQAs are analytically challenging to identify and quantify since they commonly exist as a diverse mixture of positional and geometric (cis/trans) isomers. In this work, we utilized ion mobility spectrometry coupled with mass spectrometry to separate the various isomers before and after UV irradiation. The experimental collision cross sections were then compared with theoretical structures to differentiate and identify the diCQA isomers. Our analyses found that naturally the diCQAs existed predominantly as trans/trans isomers, but after 3 h of UV irradiation, cis/cis, cis/trans, trans/cis, and trans/trans isomers were all present in the mixture. This is the first report of successful differentiation of cis/trans diCQA isomers individually, which shows the great promise of IMS coupled with theoretical calculations for determining the structure and activity relationships of different isomers in drug discovery studies.


Endothelial nitric oxide synthase is a molecular vascular target for the Chinese herb Danshen in hypertension.
Danshen, a Chinese herb, reduces hypertension in Oriental medicine. We hypothesized that Danshen acts partially through endothelial nitric oxide synthase (eNOS) signaling mechanisms. We tested the hypothesis using tanshinone II(A), an active ingredient of Danshen, and the two-kidney, one-clip renovascular hypertension model in hamsters. Oral tanshinone (50 microg/100 g body wt) reduced mean arterial pressure (MAP) from 161.2 +/- 6.9 to 130.0 +/- 7.8 mmHg (mean +/- SE; P < 0.05) in hypertensive hamsters. MAP in sham-operated hamsters was 114.3 +/- 9.2 mmHg. Topical tanshinone at 1 microg/ml and 5 microg/ml increased normalized arteriolar diameter from 1.00 to 1.25 +/- 0.08 and 1.57 +/- 0.11, respectively, and increased periarteriolar nitric oxide concentration from 87.1 +/- 11.3 to 146.9 +/- 23.1 nM (P < 0.05) at 5 microg/ml in hamster cheek pouch. N(G)-monomethyl-L-arginine inhibited tanshinone-induced vasodilation. Hypertension reduced eNOS protein relative to sham-operated control. Tanshinone prevented the hypertension-induced reduction of eNOS and increased eNOS expression to levels higher than sham-operated control in hamster cheek pouch. Topical tanshinone increased normalized arteriolar diameter from 1.0 to 1.47 +/- 0.08 in the cremaster muscle of control mice and to 1.12 +/- 0.13 in cremasters of eNOS knockout mice. In ECV-304 cells transfected with eNOS-green fluorescent protein, tanshinone increased eNOS protein expression 1.35 +/- 0.05- and 1.85 +/- 0.07-fold above control after 5-min and 1-h application, respectively. Tanshinone also increased eNOS phosphorylation 1.19 +/- 0.07- and 1.72 +/- 0.20-fold relative to control after 5-min and 1-h application. Our data provide a basis to understand the action of a Chinese herb used in alternative medicine. We conclude that eNOS stimulation is one mechanism by which tanshinone induces vasodilation and reduces blood pressure.


Obesity in preschool children: an intervention programme in primary health care in Singapore.
The Programme on Prevention and Management of Obesity in Preschool Children, aged three to six years, was implemented in 17 Primary Health Clinics in November 1991. The study sample comprised 1128 preschool children who qualified to enter the obesity register, using the defined criteria for obesity of 2 standard deviations above the normal weight for height and age. This group was divided into three categories, namely, mildly overweight (120% to below 140%), moderately overweight (140% to below 160%), and severely overweight (above 160%). The severely overweight category was referred to dietitians for follow-up management, while the other two categories were managed by the clinic staff through pre-planned nurse-conducted counselling sessions. In this paper, we analysed the first 1128 preschool children aged three to six years on the Programme with respect to their demographic characteristics; medical conditions; family history of obesity, diabetes, hypertension and ischaemic heart disease; number of siblings and parents' educational and occupational status. The Malay children showed significantly more severe grades of obesity compared to the Chinese and Indian children. A family history of obesity and hypertension among the three groups were significant (P < 0.001). After one year of follow-up with the intervention programme, the following were found: 40.4% (456) of the children improved in their obesity status and 20.2% (228) reached normal status. The severe, moderate and mild categories reduced from 6.3% to 5.9%, 29.3% to 23.2% and 64.4% to 50.7% respectively and was found to be statistically significant (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Defining Local Chemical Conditions in Magnetosomes of Magnetotactic Bacteria.
Defining chemical properties of intracellular organelles is necessary to determine their function(s) as well as understand and mimic the reactions they host. However, the small size of bacterial and archaeal microorganisms often prevents defining local intracellular chemical conditions in a similar way to what has been established for eukaryotic organelles. This work proposes to use magnetite (Fe3O4) nanocrystals contained in magnetosome organelles of magnetotactic bacteria as reporters of elemental composition, pH, and redox potential of a hypothetical environment at the site of formation of intracellular magnetite. This methodology requires combining recent single-cell mass spectrometry measurements together with elemental composition of magnetite in trace and minor elements. It enables a quantitative characterization of chemical disequilibria of 30 chemical elements between the intracellular and external media of magnetotactic bacteria, revealing strong transfers of elements with active influx or efflux processes that translate into elemental accumulation (Mo, Se, and Sn) or depletion (Sr and Bi) in the bacterial internal medium of up to seven orders of magnitude relative to the extracellular medium. Using this concept, we show that chemical conditions in magnetosomes are compatible with a pH of 7.5-9.5 and a redox potential of -0.25 to -0.6 V.


Space radiation protection: Destination Mars.
National space agencies are planning a human mission to Mars in the XXI century. Space radiation is generally acknowledged as a potential showstopper for this mission for two reasons: a) high uncertainty on the risk of radiation-induced morbidity, and b) lack of simple countermeasures to reduce the exposure. The need for radiation exposure mitigation tools in a mission to Mars is supported by the recent measurements of the radiation field on the Mars Science Laboratory. Shielding is the simplest physical countermeasure, but the current materials provide poor reduction of the dose deposited by high-energy cosmic rays. Accelerator-based tests of new materials can be used to assess additional protection in the spacecraft. Active shielding is very promising, but as yet not applicable in practical cases. Several studies are developing technologies based on superconducting magnetic fields in space. Reducing the transit time to Mars is arguably the best solution but novel nuclear thermal-electric propulsion systems also seem to be far from practical realization. It is likely that the first mission to Mars will employ a combination of these options to reduce radiation exposure.


Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer.
Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physico-chemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell internalization capability, and highly controlled release profile in response to application of focused ultrasound energy. Using an in vitro model of hepatocellular carcinoma and an in vivo large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach.


Relation between psychoneuroendocrine profile in stressful conditions and antibodies to herpesvirus 6 and 7.
The aim of the present study is to evaluate whether the individual susceptibility to infectious disease is influenced by the psychological profile of cadets exposed to stressful events associated with military lifestyle in academy and if the neuroendocrine responses to stressful events is related with humoral immunity estimated by measuring antibody titres to human herpesvirus (HHV-6)7 (HHV-7) and to what extent it is influenced by personality traits. It has been observed that cadets with lower psychoaptitude scores (1-2) have a significant higher susceptibility to infectious disease (x2=7.95; p=0.019) compared to subjects with higher scores. A positive relationship between cortisol and antibody titers to HHV-6 (r=0.304; p=0.024) it has been found. It can be interesting to observe that antibody titers on HHV-6 are also related to psychoaptitude profile (r=0.239; p=0.044). The antibody titers to HHV-7 are negatively related to the 5 scales of BFQ and in particular with subdimension Co (cordiality) of BFQ (r=0.401; p=0.002). The survey carried out on over 1,500 cadets of the Military Academy of Modena shows that the susceptibility to infectious diseases during the first six months of admission to the Academy seem to be influenced by the psychoaptitudinal profile. The finding of a positive relationship between serum cortisol and antibody vs HHV-6 suggests that the impairment of the immune system linked to circulatory cortisol levels may induce a reactivation of a latent herpesvirus 6 with related increase of antibody titers.


Stabilized ubisemiquinone in reconstituted succinate ubiquinone reductase.
QP-S, a ubiquinone (Q) protein, accepts electrons from succinate through succinate dehydrogenase (SDH). A new method has produced a preparation of QP-S which has a different amino acid composition and SDS gel electrophoretic pattern from that of the old preparation (Biochemistry 19, 3579-3585 (1980)). The new preparation contains less than 1 nmol heme/mg protein; the activity of the preparation was not proportional to its heme content. A thenoyltrifluoroacetone sensitive free radical signal was detected by EPR spectroscopy in succinate-Q reductase reconstituted from this QP-S and SDH; the characteristics of this species identify it as ubisemiquinone. At pH 7.4, the Em of the two electron step was about 70 mV with E1 = 5 mV and E2 = 125 mV. The properties of the radical differed slightly from those of "Qs" radical in more intact preparations (e.g. submitochondrial particles). The present is the simplest system in which such a succinate reducible ubisemiquinone free radical has been demonstrated.


Malignant melanoma of the left nasal fossa - case report.
Mucosal malignant melanoma is an extremely rare tumor of the nose, with an aggressive character, low prognosis and frequent recurrences. The authors present a case of a 60-year-old male patient, diagnosed five years ago with adenoid cystic carcinoma, for which he had surgery and radiotherapy, who was admitted in our Clinic with unilateral epistaxis and obstruction of the nasal cavity. Clinical exam revealed an obstructive polypoidal bleeding mass of the left nasal cavity. Biopsy was performed and the histopathological exam showed malignant mucosal melanoma. Wide local endoscopic surgery was practiced for two times in the last two years, and for now, there is no recurrence. Malignant melanomas are tumors with high mortality rate, which necessitate an early diagnosis and immediate treatment.


Marital Transitions, Parenting, and Schooling: Exploring the Link Between Family-Structure History and Adolescents' Academic Status.
The linkage between family structure and adolescents' academic experiences is part of a larger, dynamic process unfolding over time. To investigate this phenomenon, this study drew on the National Longitudinal Study of Adolescent Health and the Adolescent Health and Academic Achievement Study. Logistic regressions revealed that family structure at birth predicted students' academic status in math in the ninth grade, and multinomial regressions revealed that family instability, along with curricular location in the ninth grade, parenting behaviors, and adolescents' adjustment and aspirations, distinguished those who completed higher-level math by the end of high school from those who did not but still graduated from high school and from those who dropped out of high school.


Is territorial expansion a mechanism for crossmodal plasticity?
Crossmodal plasticity is the phenomenon whereby, following sensory damage or deprivation, the lost sensory function of a brain region is replaced by one of the remaining senses. One of several proposed mechanisms for this phenomenon involves the expansion of a more active brain region at the expense of another whose sensory inputs have been damaged or lost. This territorial expansion hypothesis was examined in the present study. The cat ectosylvian visual area (AEV) borders the auditory field of the anterior ectosylvian sulcus (FAES), which becomes visually reorganized in the early deaf. If this crossmodal effect in the FAES is due to the expansion of the adjoining AEV into the territory of the FAES after hearing loss, then the reorganized FAES should exhibit connectional features characteristic of the AEV. However, tracer injections revealed significantly different patterns of cortical connectivity between the AEV and the early deaf FAES, and substantial cytoarchitectonic and behavioral distinctions occur as well. Therefore, the crossmodal reorganization of the FAES cannot be mechanistically attributed to the expansion of the adjoining cortical territory of the AEV and an overwhelming number of recent studies now support unmasking of existing connections as the operative mechanism underlying crossmodal plasticity.


Clomipramine treatment of obsessive-compulsive disorder. II. Biochemical aspects.
Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the dopamine metabolite homovanillic acid, and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol were measured in CSF before and after three weeks' treatment of severe obsessive-compulsive disorder with clomipramine hydrochloride. Patients who responded to clomipramine treatment had significantly higher CSF levels of 5-HIAA before treatment. The amelioration of obsessive-compulsive symptoms was positively correlated to the reduction of CSF concentrations of 5-HIAA during clomipramine treatment but negatively correlated to plasma concentrations of clomipramine. Reduction of CSF concentrations of 5-HIAA, which probably reflects drug action on central serotonin neurons, was maximal at a plasma clomipramine concentration of about 300 nmole/L. At higher levels, the reduction of CSF levels of 5-HIAA was smaller. The antiobsessive effect of clomipramine may be connected to its capacity to inhibit serotonin uptake.


Emerging drugs for celiac disease.
Celiac disease is an immune-mediated gluten-dependent disorder, primarily affecting the small intestine in genetically predisposed individuals. The disorder has a very heterogeneous clinical and histopathological spectrum. Current treatment with a gluten-free diet is very effective, but the diet is difficult to maintain and remains costly. Alternatives to the gluten-free diet have been proposed to either replace this current treatment, or at least, to supplement use of the gluten-free diet. Studies in the published English language literature relevant to this review were examined for this report. Most recent published double-blind, placebo-controlled clinical trials have focused on an orally administered recombinant glutenase (ALV003) showing significant but limited benefit to celiac disease patients already compliant with a gluten-free diet. Other studies have addressed other immune mechanisms that may play a role in its pathogenesis and have not been so positive. Added investigations, particularly over the long-term, in other larger and more heterogeneous populations are needed.