Structural studies of the capsular polysaccharide and lipopolysaccharide O-antigen of Aeromonas salmonicida strain 80204-1 produced under in vitro and in vivo growth conditions.
Aeromonas salmonicida is a pathogenic aquatic bacterium and the causal agent of furunculosis in salmon. In the course of this study, it was found that when grown in vitro on tryptic soy agar, A. salmonicida strain 80204-1 produced a capsular polysaccharide with the identical structure to that of the lipopolysaccharide O-chain polysaccharide. A combination of 1D and 2D NMR methods, including a series of 1D analogues of 3D experiments, together with capillary electrophoresis-electrospray MS (CE-ES-MS), compositional and methylation analyses and specific modifications was used to determine the structure of these polysaccharides. Both polymers were shown to be composed of linear trisaccharide repeating units consisting of 2-acetamido-2-deoxy-D-galacturonic acid (GalNAcA), 3-[(N-acetyl-L-alanyl)amido]-3,6-dideoxy-D-glucose[3-[(N-acetyl-L-alanyl)amido]-3-deoxy-D-quinovose, Qui3NAlaNAc] and 2-acetamido-2,6-dideoxy-D-glucose (2-acetamido-2-deoxy-D-quinovose, QuiNAc) and having the following structure: [-->3)-alpha-D-GalpNAcA-(1-->3)-beta-D-QuipNAc-(1-->4)-beta-D-Quip3NAlaNAc-(1-]n, where GalNAcA is partly presented as an amide and AlaNAc represents N-acetyl-L-alanyl group. CE-ES-MS analysis of CPS and O-chain polysaccharide confirmed that 40% of GalNAcA was present in the amide form. Direct CE-ES-MS/MS analysis of in vivo cultured cells confirmed the formation of a novel polysaccharide, a structure also formed in vitro, which was previously undetectable in bacterial cells grown within implants in fish, and in which GalNAcA was fully amidated.


Reaction of the C3(X(1)Σg (+)) carbon cluster with H2S(X(1)A1), hydrogen sulfide: photon-induced formation of C3S, tricarbon sulfur.
In this paper we report on the neutral-neutral reaction of the C3 carbon cluster with H2S in solid inert argon at 12 K, conditions that mimic, in part, the surfaces of interstellar grains. In the first step of the reaction, a C3•H2S complex is formed via an almost barrierless entrance addition mechanism. This complex, stabilized by an estimated 7.45 kJ/mol (CCSD(T)/aug-cc-pVTZ//B3LYP/6-311++G(d,p) level), is formed by the interaction of a terminal carbon of C3 with a hydrogen in H2S. This con-covalent complex displays a band at 2044.1 cm(-1) observed via Fourier transform infrared absorption spectroscopy. With the help of the MP2/aug-ccpVDZ level method, this band is assigned to the CC asymmetric vibration mode. When the complex is exposed to UV-visible photons (hν < 5.5 eV) the tricarbon sulfur C3S molecule is identified, based on the appearance of a characteristic CC stretching band at 2047.5 cm(-1). Calculated ground-state potential energy surfaces also confirm the concomitant formation of molecular H2. This facile reaction pathway involves an attainable transition state of 174.4 kJ/mol. Conversely, competing lower-energy reaction pathways that would lead to the generation of H2C3S (propadienethione), or C2H2 (acetylene) and CS, involve much more complex, multi-stage pathways, and are not observed experimentally.


Interactive effect of temperature and plant species on nitrogen cycling and treatment in stormwater biofiltration systems.
Stormwater biofiltration systems (also known as biofilters, bioretention, rain gardens) are engineered nature-based solutions, which help mitigate aquatic nitrogen pollution arising from storm runoff. These systems are being increasingly used in a range of climates across the world. A decline in treatment performance is frequently observed in cold weather conditions. While plant species comprise an important design factor influencing system performance, the effect of temperature on the fate of dissolved nitrogen forms, namely ammonium (NH4+) and nitrate (NO3-), in the presence of different plant species in these systems remains unclear. A large scale laboratory experiment was undertaken that measured potential rates of nitrification, denitrification and dissimilatory nitrate reduction to ammonium (DNRA) as well as the microbial community structure to investigate nitrogen fate and hence removal under two different temperature conditions (2 °C and 15 °C) in the presence of four distinct plant species. The results indicate that lower nitrification rates (reduced by a factor of 4) coupled with potential media NH4+ desorption could be contributing to reduced NH4+ removal during cold conditions. Planting with species exhibiting good nutrient uptake capacity can reduce the extent of this performance decline. While NO3- reduction generally remains problematic during cold weather (<0 to 55% reduction), which may not be significantly different from warmer periods, the study demonstrated that the denitrification potential and gene abundance (nap, nar, NirS, norB, nosZ) to be higher than those of nitrification (amoA). Denitrification may not proceeding at optimal rates due to lack of conducive environmental conditions. Nitrogen transformation via DNRA was found to be relatively insignificant. Future studies should investigate the potential of employing cold-resilient plant species to maintain both NH4+ and NO3- removal in cold weather conditions.


A cross-sectional analysis of executive function in Down syndrome from 2 to 35 years.
Previous research has indicated a unique profile of executive function (EF) in children and adolescents with Down syndrome (DS). However, there is a paucity of research on EF in adults with DS. This study aimed to gain a broader understanding of strengths and weaknesses in EF in DS from 2 to 35 years. Parents of 112 individuals with DS between 2 and 35 years participated in this study. Parents either completed the Behaviour Rating Inventory of Executive Function - for individuals 6+ years - or the Behaviour Rating Inventory of Executive Function Preschool Version - for children 2-5 years. Results suggest not only overall difficulties but also patterns of strength and weakness within EF for individuals with DS. For the 2 to 5-year-old group, emotional control and shift were relative strengths, planning/organisation and inhibit were intermediate skills, and working memory was a relative weakness. For the 6 to 18-year-old group, emotional control and organisation of materials were relative strengths, inhibit and initiate were intermediate skills, and working memory, monitor, planning/organisation, and shift were relative weaknesses. Most abilities were consistent from 2 to 18 years, except shift, which decreased in preadolescence before beginning to recover in adolescence. Across the full age range (2-35 years), composite scores indicated quadratic trends in inhibit, working memory, and planning/organisation, and a cubic trend in shift, with EF abilities generally declining in middle childhood before recovering in adulthood. This study extends previous research on EF in DS by providing an initial description of EF profiles across the lifespan. More longitudinal and behavioural research is needed to further characterise the development of EF in DS.


Diagnostic sensitivity of direct wet mount microscopy for soil-transmitted helminth infections in Jimma Town, Ethiopia.
Soil-transmitted helminthiasis (STH) remains a major public health problem in school children in Ethiopia. Although direct wet mount microscopy (DWMM) is the means to diagnose parasitic diseases in health care facilities in Ethiopia, it remains unclear what its diagnostic performance is for STH. A cross-sectional study was performed in Jimma Town (Ethiopia) and included 600 children from 10 primary schools. The diagnostic sensitivity of DWMM was compared to a composite reference standard (CRS) consisting of Kato-Katz, McMaster and Mini-FLOTAC. We also explored the impact of intensity of infection (the highest faecal egg counts (FECs; expressed as eggs per gram of stool (EPG)) across the CRS) on the diagnostic sensitivity of DWMM. Based on the CRS, there were 210 Ascaris (35.0%), 312 Trichuris (52.0%) and 102 hookworm cases (17.0%). The median intensity of infections equalled 2,057 EPG for Ascaris, 200 EPG for Trichuris and 110 EPG for hookworms. The sensitivity of DWMM was 73.8% for Ascaris, but was around 17% for both Trichuris and hookworms. The sensitivity significantly increased with intensity of STH. For Ascaris, the odds for detecting an infection intensity of 1,000 EPG was 6.2 times higher than detecting an infection of 100 EPG. For Trichuris and hookworms, these odds ratios were 7.1 and 14. The diagnostic sensitivity of DWMM is low for STH, but it is able to detect those subjects that are in the highest need of treatment, and hence contributes to the global goal to eliminate STH as a public health problem.


Effects of employer management on employee recruitment, satisfaction, engagement, and retention on large US dairy farms.
Lack of employee engagement and satisfaction and high turnover rate of employees are major problems on some US dairy farms. Farm adoption of human resource management (HRM) practices varies widely. Using feedback from 168 employees from 12 large dairy farms, our objectives were to understand employee perceptions of HRM strengths and weaknesses and their influence on (1) employee satisfaction, (2) retention of employees, (3) willingness of employees to recommend the farm as a place to work, and (4) level of employee engagement on the farm. Employees who rated their employers higher for almost any management-related question (MRQ) were more satisfied in their jobs and more likely to recommend their place of work to other potential employees. Employees reported a higher intention to stay on the farm when employers scored higher on MRQs connected to employer-employee relationships. Employees who rated "Relationships" (a component consisting of 5 MRQs) higher were more likely to have a higher rate of satisfaction, were more likely to intend to stay at their job, and were more likely to recommend their place of work to others. No single management question was positively related to employee engagement (as measured by employees having and sharing ideas to improve the business); however, ethnicity, gender, job role, duration of employment, and employee's self-appraisal of their desire to learn and commitment to the farm were each associated with engagement. Female employees were less likely to provide ideas to their employers (compared with male employees), as were Spanish-speaking employees (compared with English-speaking employees). Differences between Spanish- and English-speaking employees were also present in measures such as intention to stay (shorter) and willingness to recommend the farm as a place to work (higher). Employees who rated themselves higher on their desire to learn and commitment to the farm were more likely to provide ideas to their employers, as were longer-term employees. In conclusion, we inferred that dairy farm management can improve employee retention and engagement through improved use of HRM practices.


Design and performance test of variable diameter threshing drum of combine harvester.
During the rice harvesting process of combine harvester, it is necessary to adjust the working parameters of the threshing device in time according to working conditions to ensure operational efficiency and performance. This paper designs a variable diameter threshing drum, develops a device for diameter regulation with self-locking function, and its installation process and working principle are introduced in detail. A force analysis and modal analysis were carried out on the device for diameter adjustment of variable diameter threshing drum. It aims to ensure that the design dimensions of the constant speed spiral disc and claws in the device for diameter adjustment are in compliance with the self-locking conditions, and effectively ensure the reliability of the device for diameter adjustment. A field experiment was carried out to check the reliability of the developed system. A regression analysis model takes the feeding rate, threshing gap and drum speed as influencing factors. The grain separation loss rate and damage rate as performance indexes were established, and calculations for multiple target optimization were performed. The experimental results showed that the threshing gap could be adjusted in real time according to the different feeding rates of the variable diameter threshing drum.


A stable N-heterocyclic carbene organocatalyst for hydrogen/deuterium exchange reactions between pseudoacids and deuterated chloroform.
It was observed that the stable and commercially available N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene, the so-called IDipp, catalyzes hydrogen/deuterium exchange reactions between pseudoacids and chloroform-d1, while the analogous saturated NHC 1,3-bis(2,4,6-trimethylphenyl)imidazolin-2-ylidene, the so-called SIMes, is inefficient for the same transformation. Experimental and computational DFT studies allowed these differences of reactivity to be attributed to the relative stability of the corresponding azolium–trichloromethyl anion ion pairs: in the former case, the complex evolves toward dissociation of the ions to produce an aromatic azolium cation and a basic trichloromethyl anion, while in the latter case, it evolves by ion recombination to give the product of formal carbene C–H insertion into the C–H bond of chloroform. These results provide a rationale for some early intuitions and observations of Wanzlick, Arduengo, and others on the reactivity of NHCs with chloroform as well as a simple organocatalytic method for the deuteration of pseudoacids (pKa,DMSO = 14–19) with chloroform-d1.


Surveillance computed tomography imaging and detection of relapse in intermediate- and advanced-stage pediatric Hodgkin's lymphoma: a report from the Children's Oncology Group.
PURPOSE Children with Hodgkin's lymphoma (HL) routinely undergo surveillance computed tomography (CT) imaging for up to 5 years after therapy, resulting in cost and radiation exposure, without clear benefit. The objective of this study was to determine the contribution of surveillance CT, as compared with clinical findings, to detection of disease recurrence. PATIENTS AND METHODS Two hundred sixteen patients, age ≤ 21 years old, were treated on the multicenter Pediatric Oncology Group 9425 trial. Data for patients who experienced relapse were retrospectively reviewed to determine whether imaging or clinical events prompted suspicion of disease recurrence. Correlation was made to disease stage, time to recurrence, relapse site, and overall survival (OS). Results With a median follow-up time of 7.4 years, 25 (11.6%) of 216 patients had experienced a relapse, of whom 23 experienced local relapse. Median time to relapse was 7.6 months (range, 0.2 to 48.9 months). Nineteen relapses (76%) were detected based on symptoms, laboratory or physical examination findings, and two relapses (8%) were detected by imaging within the first year after therapy. Only four patients (16%) had their recurrence detected exclusively by surveillance imaging after the first year. Six deaths occurred, all in patients who experienced relapse within the first year after therapy. No patient with a recurrence after 1 year off treatment has died, regardless of how the recurrence was detected. CONCLUSION The majority of pediatric HL relapses occurred within the first year after therapy or were detected based on change in clinical status. Detecting late relapse, whether by imaging or clinical change, did not affect OS. These findings indicate that CT is overused for routine surveillance of patients with HL.


Different influences of two types of diets commonly used for rats on a series of parameters related to the metabolism of central serotonin and noradrenaline.
A commercial chow and a semipurified diet fed for 14 days to Sprague-Dawley male rats kept under standardized conditions of temperature, humidity, and light had different effects on a series of parameters related to the metabolism of central serotonin and noradrenaline. Rats fed the commercial chow had (1) a lower serum level of the six neutral amino acids (valine, isoleucine leucine, tyrosine, phenylalanine, and methionine) known to compete with tryptophan for its entry into the brain, (2) a higher ratio of tryptophan to the sum of the six neutral amino acids, (3) a lower ratio of tyrosine to the other five neutral amino acids, (4) a lower ratio of serotonin to 5-hydroxyindoleacetic acid in hypothalamus, (5) a higher tryptophan hydroxylase activity in raphe nuclei, and (6) a higher content of noradrenaline in hypothalamus. It is suggested that chow fed rats had a more active central serotonin metabolism in hypothalamus than rats fed the semipurified diet.


Bimetallic Molecular Catalyst Design for Carbon Dioxide Reduction.
The core challenge in developing cost-efficient catalysts for carbon dioxide (CO2 ) conversion mainly lies in controlling its complex reaction pathways. One such strategy exploits bimetallic cooperativity, which relies on the synergistic interaction between two metal centers to activate and convert the CO2 substrate. While this approach has seen an important trend in heterogeneous catalysis as a handle to control stabilities of surface intermediates, it has not often been utilized in molecular and heterogenized molecular catalytic systems. In this review, we gather general principles on how natural CO2 activating enzymes take advantage of bimetallic strategy and how phosphines, cyclams, polypyridyls, porphyrins, and cryptates-based homo- and hetero-bimetallic molecular catalysts can help understand the synergistic effect of two metal centers.


CJ-21,164, a new D-glucose-6-phosphate phosphohydrolase inhibitor produced by a fungus Chloridium sp.
A new D-glucose-6-phosphate phosphohydrolase (G6Pase) inhibitor, CJ-21,164 (1) was isolated from the fermentation broth of the fungus Chloridium sp. CL48903. The structure was elucidated to be a novel tetramer of the salicylic acid derivatives by spectroscopic analyses. Compound I inhibited G6Pase in rat liver microsomes with an IC50 of 1.6 microM. Glucose output from hepatocytes isolated from rat liver was inhibited when I was present in the incubation medium, consistent with the role of I as a G6Pase inhibitor.


[The nurse's paradox or the virtue of care cessation].
Between treatment which brings no improvement or which can even result in dangerous side effects and the lethal risk of the disease itself, the nurse is often faced with delicate situations. They must examine their conscience and choose between ministering treatment at all costs and not applying a medical prescription.


Investigation of finite-size effects in chemical bonding of AuPd nanoalloys.
In this paper, the size-dependent changes in energetic, vibrational, and electronic properties of C-O gas molecule interacting with surface Pd atom of a variety of AuPd nanoalloy structures are investigated by means of first principles calculations. The variation in C-O adsorption energies, C-O vibration frequencies (νC-O), and Pd d-bond centers (εd) on a series of non-supported Aun-1-Pd1 nanoparticles (with n varying from 13 to 147) and on two semi-finite surfaces are inspected with cluster size. We demonstrate for the first time that, with small AuPd bimetallic three-dimensional clusters as TOh38, one can reach cluster size convergence even for such a sensitive observable as the adsorption energy on a metal surface. Indeed, the results show that the adsorbate-induced perturbation is extremely local and it only concerns the isolated Pd interacting with the reactive gas molecule. Except for 13 atom clusters, in which molecular behaviour is predominant, no finite-size effects are observed for surface Pd atom substituted in AuPd free nanoclusters above 38 atoms.


[Antigenicity of hepatitis C virus F protein and serum prevalence of anti-F in HCV-infected patients].
To examine the antigenicity of hepatitis C virus (HCV) F protein and investigate serum prevalence of anti-F in HCV-infected patients. Eleven pairs of overlapping primers were used to synthesize the full-length HCV f gene, from which the truncated HCV f65 gene fragment was amplified by PCR. HCV f65 gene was then cloned into pET32a(+), and transformed into E. coli strain Plyss (DE3). This recombinant E.coli was induced by IPTG for the production of HCV F65 protein. The expressed HCV F65 protein, purified by Ni-NTA agarose, was further used in ELISA to detect serum anti-F, and to immunize rabbits for making polyclonal anti-F. The rabbit polyclonal anti-F was purified by Staphylococcus aureus protein A agarose. After recombinant pET32a(+)-f65 was constructed successfully, HCV F65 protein was expressed and purified. The purified HCV F65 protein was used as a capture antigen in ELISA to detect serum anti-F in HCV infected patients (n = 30). The result showed that the mean A450 value and the positive rate of serum anti-F were 0.125+/-0.061 and 63.3%, respectively. The rabbit-derived polyclonal anti-F reacted specifically with HCV F65 protein, of which the titer was 1:30,000. Our expressed HCV F65 protein is of antigenicity, and can be used to determine serum anti-F. Anti-F IgG does exist in the sera of the HCV-infected patients. Moreover, the rabbit-derived polyclonal anti-F can be used to detect HCV F protein.


Specificities involved in the initiation of retroviral plus-strand DNA.
Reverse transcription of the retroviral RNA genome begins with tRNA-primed synthesis of a minus-strand DNA, which subsequently acts as the template for the synthesis of plus-strand DNA. This plus-strand DNA is initiated at a unique location and makes use of a purine-rich RNA oligonucleotide derived by RNase H action on the viral RNA. To determine the variables that are relevant to successful specific initiation of plus-strand DNA synthesis, we have used nucleic acid sequences from the genome of Rous sarcoma virus along with three different sources of RNase H: avian myeloblastosis virus DNA polymerase, murine leukemia virus DNA polymerase, and the RNase H of Escherichia coli. Our findings include evidence that specificity is controlled not only by the nucleic acid sequences but also by the RNase H. For example, while the avian reverse transcriptase efficiently and specifically initiates on the sequences of the avian retrovirus, the murine reverse transcriptase initiates specifically but at a location 4 bases upstream of the correct site.


The Effect of Paracetamol versus Meperidine on Postoperative Pain of Cesarean Section.
Meperidine and paracetamol are frequently used in postoperative pain control. We evaluated the effect of paracetamol versus meperidine on postoperative pain control of elective cesarean section in patients under general anesthesia. In this randomized double-blind study, seventy mothers' candidate for cesarean section under general anesthesia were randomized in paracetamol group (n = 35), received 1 g paracetamol in 100 ml normal saline, and meperidine group (n = 35), received 25 mg meperidine in 100 ml normal saline and then compared regarding the pain and vomiting severity based on visual analog scale (VAS). Two groups did not show significant difference regarding pain score based on VAS during 30 min after surgery in the recovery room, however, the pain score after 30 min in paracetamol group was significantly more than meperidine group. The difference between two groups regarding pain score in surgery ward at 0, 2, 4, 6 h, were not significant, however, pain score after 6 h in meperidine group was significantly lower than paracetamol group. The score of vomiting based on VAS in the recovery room in meperidine group was marginally more than paracetamol group (P > 0.05). The score of vomiting, based on VAS in meperidine group was significantly more than paracetamol group during the 24 h in the surgery ward. The analgesic consumption in meperidine group during 24 h after surgery was significantly lower than paracetamol group. We indicated that the meperidine decreased postoperative pain score and analgesic consumption more than paracetamol, but increased the vomiting score.


Effects of supplementing Holstein cows with soybean oil compared with palmitic acid-enriched triglycerides on milk production and nutrient partitioning.
Both insulin and trans-10,cis-12 C18:2 (t10c12CLA) can be increased by high-starch diets; thus, it is difficult to determine whether insulin or t10c12CLA mediates nutrient partitioning toward body tissues during milk fat depression. To minimize insulin secretion while manipulating t10c12CLA levels, diets supplemented with palmitic acid-enriched triglycerides and soybean oil were fed to cows. Thirty-two Holstein cows (93 ± 35 d in milk) were included in the crossover experiment with each treatment period being 28 d. Treatment diets contained 25% neutral detergent fiber, 32% starch, 18% crude protein, and 4.6% fatty acids (dry matter basis). Treatment diets contained either palmitic acid-enriched triglycerides (2.5% dry matter, BergaFat T-300, Berg + Schmidt America LLC, Libertyville, IL; PAT) or soybean oil (2.5% dry matter; SBO). Cows were blocked by milk yield, body weight, and parity, and then randomly assigned to 1 of 2 treatment sequences (PAT-SBO or SBO-PAT). Cows fed PAT produced milk with only 3.1% fat, indicating milk fat depression; SBO decreased fat content further to only 2.4%. No effect of treatment was observed on dry matter intake, apparent net energy intake, milk yield, body condition score, or fat thickness over the rump and rib. However, compared with PAT, SBO decreased fat-corrected milk yield, energy-corrected milk yield, milk fat yield, de novo fatty acids, and 16-carbon fatty acid yield, whereas SBO increased body weight gain. Neutral detergent fiber digestibility tended to be lower in SBO, whereas fatty acid digestibility was higher. Additionally, the concentration of plasma insulin, nonesterified fatty acids, and triglycerides, and milk metabolites (trans-10 C18:1 and t10c12CLA) were all higher in SBO. In conclusion, with similar dietary starch content, the diet containing palmitic acid-enriched triglycerides partitioned more energy toward milk synthesis, whereas the diet containing soybean oil partitioned more energy toward body tissue gain.


One-Pot Method for the Synthesis of 2,5-Unsubstituted Pyrrolidino[3',4':1,9]fullerenes.
A new, efficient process has been developed for the preparation of 2,5-unsubstituted pyrrolidino[3',4':1,9]fullerenes by the Ti(O-i-Pr)4-promoted reaction of fullerene C60 with 1,3,5-perhydrotriazines generated in situ upon the reaction of primary alkyl- and benzylamines with paraformaldehyde and EtMgBr.


The acutely decompensated right ventricle: pathways for diagnosis and management.
Decompensated right ventricular (RV) failure is becoming increasingly common as the prevalence of predisposing conditions grows. Advances in diagnosis and management have granted insights into the following pathophysiologic mechanisms of RV dysfunction: impaired RV contractility, RV pressure overload, and RV volume overload. Emerging imaging modalities, such as cardiac MRI, and new therapeutic agents, such as pulmonary selective vasodilators, have expanded our options for evaluation and management, respectively. An improved understanding of pathophysiology and technologic progress provides us with new pathways in the diagnosis and hemodynamic support of these often critically ill patients.


[Endocrine disorders in toxic goiter in the postoperative period].
The disturbances of endocrinous functions in patients with toxic goiter in the early postoperative period were more pronounced in the critical state and in the average gravity of the disease. The endocrinous disorders revealed were well corrected by antithyroid drugs, corticosteroids, neuroleptics and beta-adrenoblockers and in most of the patients they were found to disappear or to reduce to the preoperative level within 8 days after operation.


Asymmetric Michael Reaction of α-CF3 Thioester and α,β-Unsaturated Aldehyde Catalyzed by Diphenylprolinol Silyl Ether.
Asymmetric Michael reaction of α-CF3 thioester and α,β-unsaturated aldehyde is catalyzed by diphenylprolinol silyl ether to afford the trifluoromethyl substituted Michael product with excellent enantioselectivity. Although the Michael products were generated as a mixture of syn- and anti-isomers, they can be transformed to single isomers of other useful compounds, such as lactone, lactam, piperidine, dihydropyran containing trifluoromethyl groups, or fluoro substituents.


Dissecting susceptibility from exogenous triggers: the model of alopecia areata and associated inflammatory skin diseases.
Alopecia areata (AA) is a T-cell-driven autoimmune disease of the hair follicle and frequently reported to be associated with inflammatory skin diseases (ISD) such as atopic eczema (AE) or psoriasis. Interestingly, AA on the one hand and both AE and psoriasis on the other hand are believed to be driven by mutually antagonistic T-cell subsets. To characterize AA-specific T-cell profiles and inflammatory pattern by intra-individual comparison of AA and coexistent ISD. 112 patients with AA were recruited and investigated for coexisting ISD. In-depth analyses were performed in patients with AA and AE (n = 2), AA and psoriasis (n = 1), AA and psoriasis and AE (n = 1) and AA and lichen planus (n = 1), using histology, immunohistochemistry and cytokine staining of T cells isolated from lesional skin. Of 112 AA patients investigated, 23 suffered from an ISD. The prevalence of AE, vitiligo, psoriasis and lichen planus was higher in the investigated AA cohort than in the normal population. The clinical as well as histological phenotype of AA the coexistent ISD were unequivocal. In line with this, T-cell infiltrates were found to be disease-characteristics with AA and lichen planus dominated by CD8+ and IFN-γ+ TNF-α+ producing T cells while psoriasis lesions in the same patients were dominated by IL-17+ and AE by IL-4+ T cells. AA patients have a higher incidence of various T-cell-driven inflammatory skin diseases than the normal population, a phenomenon which might relate to over-activation of skin-homing T cells and to specific immune triggers as the primary cause of inflammation. More importantly, we showed that by using AA as a model disease, our approach of intra-individual comparison of distinct inflammatory responses in the same patient is feasible and offers the unique possibility to gain insights into disease pathogenesis independent from genetic susceptibilities.


Modulation of c-myc, c-myb, c-fos, c-sis and c-fms proto-oncogene expression and of CSF-1 transcripts and protein by phorbol diester in human malignant histiocytosis DEL cell line with 5q 35 break point.
Following exposure to phorbol ester (TPA), DEL cell line, a human malignant histiocytosis (MH) cell line, is able to differentiate along a macrophage phenotype and thus it provides a suitable model for analyzing the sequential and differential gene expression associated with monocyte/macrophage differentiation. C-myc, c-myb, c-fos, c-sis and c-fms expression were determined by Northern analysis at various times following TPA treatment. The results showed that TPA down-modulated the constitutive expression of c-myc, c-myb, and c-fms, mRNA to low but still detectable levels. Conversely, TPA-induced differentiation resulted in transient appearance of c-fos, whereas no change in the level of c-sis and actin transcripts were observed. Thus, the c-fms and c-sis genes appear to be regulated in a specific manner in this malignant histiocytosis derived cell line. Furthermore, these investigations demonstrated a constitutive CSF-1 gene expression which transiently increased at mRNA and also at protein level as evaluated by a murine bone marrow CFU bioassay. Through this drug-induced modulation, the DEL cell line offers an additional model for studying some of the subtle interrelations existing between a growth factor (CSF-1) and its receptor (c-fms) in the monocyte/macrophage system.


Guidelines for preventing "dilution false negatives" in in vitro laboratory testing of the donor population.
In this article we develop a calculation or formula for use in determining the potential dilution effect of fluids administered during patient treatment on serologic testing parameters. The formula uses basic principles of (a) fluid distribution over time from administration; (b) ratios of plasma and extravascular fluid volumes to body weight; and (c) common practices of fluid resuscitation. A dilution threshold of 50% was set using data from enzyme-linked immunosorbent assay human immunodeficiency virus antibody determinations performed on in vitro diluted seropositive serum samples. These data respond to issues raised by guidelines from the Centers for Disease Control and the U.S. Food and Drug Administration to achieve recipient safety without unnecessarily restricting the potential donor pool.


Impact of the dynamic and static component of the sport practised for electrocardiogram analysis in screening athletes.
To interpret the electrocardiogram (ECG) of athletes, the recommendations of the ESC and the Seattle criteria define type 1 peculiarities, those induced by training, and type 2, those not induced by training, to rule out cardiomyopathy. The specificity of the screening was improved by Sheikh who defined "Refined Criteria," which includes a group of intermediate peculiarities. The aim of our study was to investigate the influence of static and dynamic components on the prevalence of different types of abnormalities. The ECGs of 1030 athletes performed during preparticipation screening were interpreted using these three classifications. Our work revealed 62/16%, 69/13%, and 71/7% of type 1 peculiarities and type 2 abnormalities for the ESC, Seattle, and Refined Criteria algorithms, respectively(P<.001). For type 2 abnormalities, three independent factors were found for the ESC and Seattle criteria: age, Afro-Caribbean origin, and the dynamic component with, for the latter, an OR[95% CI] of 2.35[1.28-4.33] (P=.006) and 1.90[1.03-3.51] (P=.041), respectively. In contrast, only the Afro-Caribbean origin was associated with type 2 abnormalities using the Refined Criteria: OR[95% CI] 2.67[1.60-4.46] (P<.0001). The Refined Criteria classified more athletes in the type 1 category and fewer in the type 2 category compared with the ESC and Seattle algorithms. Contrary to previous studies, a high dynamic component was not associated with type 2 abnormalities when the Refined Criteria were used; only the Afro-Caribbean origin remained associated. Further research is necessary to better understand adaptations with regard to duration and thus improve the modern criteria for ECG screening in athletes.


Protargol synthesis: an in-house protocol.
The protargol staining method has proved to be indispensable for revealing the cellular structures of a variety of protozoa, especially the flagellates and ciliates. Protargol provides permanent stains of a variety of cellular structures: nuclei, extrusomes, basal bodies, and microfilamentous constituents of cells. Together with the older silver nitrate methods, protargol impregnations have provided the basis for the detailed descriptions of nearly all ciliates to date. The performance of commercially available preparations has varied widely. Recently, suppliers have stopped stocking the effective forms of protargol resulting in a worldwide shortage. Thus, it has become necessary for protistologists to explore on-site synthesis of this critically important agent. An optimum protocol for synthesis of protargol should be rapid, relatively inexpensive, simple enough to be done by non-chemists, and achievable without specialized equipment. In this article, the authors briefly review the interesting history of protargol and describe a protocol, based on the early studies of neuroanatomists, that yields a protargol producing impregnations of ciliates comparable to those obtained with previously available commercial preparations.


The effects of reverse atrial electrical remodeling on atrial defibrillation thresholds.
The implantable atrial defibrillator is a developing therapeutic option for paroxysmal atrial fibrillation, but shock related discomfort continues to be a limiting factor. To further characterize successful defibrillation, the relationship between reverse atrial electrical remodeling and internal atrial defibrillation thresholds in canines with chronic atrial fibrillation was examined. Testing was performed in 21 dogs. Chronic atrial fibrillation was induced in eight dogs by creating moderate mitral regurgitation and rapidly pacing the right atrium for > or = 6 weeks. The atrial fibrillation cycle length, atrial effective refractory period, refractory period dispersion, and internal atrial defibrillation thresholds were determined after establishment of chronic atrial fibrillation after 4 hours of sinus rhythm postcardioversion and 7 days of sinus rhythm postcardioversion. These measurements were then compared to a normal population of 13 dogs. The atrial defibrillation thresholds were 6.6 J (1.9-10.1 J) initially, 2.9 J (1.5-3.7 J) after 4 hours of sinus rhythm, and 0.9 J (0.4-1.3 J) after 7 days of sinus rhythm (P = 0.04). This decrease was associated inversely with the atrial effective refractory period (P < 0.03), and atrial fibrillation cycle length (P < 0.05), and with a decrease in atrial refractory period dispersion after 7 days of sinus rhythm (P = 0.04). These electrophysiological measurements reached normal population levels by 7 days. Atrial defibrillation thresholds decrease as atrial reverse electrical remodeling occurs and this reduction corresponds to increased atrial fibrillation cycle length, increased atrial refractoriness, and decreased refractory period dispersion.


Practical application of nonrandomized research to patient care: a case study of nesiritide.
Prospective, randomized clinical trials are the gold standard for establishing cause-and-effect relationships between therapeutic interventions and specific outcomes. Unfortunately, these types of studies are not always available to evaluate important clinical end points such as mortality. Meta-analyses and observational studies are often used in an attempt to fill the gap in the literature when no prospective, randomized trials exist to answer a research question. A rapid increase in the number of published meta-analyses and observational studies has occurred in recent years. In the absence of prospective, randomized studies, it is essential for the clinician to understand the important issues involved in interpreting these other types of studies. When evaluating a meta-analysis, the clinician should assess for several different forms of bias, clinical heterogeneity, and use of appropriate methodology. When evaluating an observational study, sources of bias and confounding should be identified. If the potential for confounding is present, the methods used to minimize the impact of confounders should be evaluated for appropriateness. Mortality associated with nesiritide in the treatment of acute decompensated heart failure is a contemporary example of the use of nonrandomized research to address a research question that is unanswered by prospective, randomized studies. We review the details of a recent meta-analysis and observational evaluation of mortality associated with nesiritide and discuss the issues that are important in critical evaluation of nonrandomized study designs.


Portal blood arterialization with an extracorporeal device to treat toxic acute hepatic failure in a swine model.
This study aimed to determine whether a controlled portal blood arterialization by a liver extracorporeal device (L.E.O2 NARDO) is effective in treating acute hepatic failure (AHF) induced through CCl4 administration in a swine model. 20 swine with AHF induced by intraperitoneal injection of carbon tetrachloride (CCl4) in oil solution, were randomly divided into two groups: animals receiving L.E.O2 NARDO treatment 48 h after the intoxication (study group); animals sham operated 48 h after the intoxication (control group). Blood was withdrawn from the iliac artery and reversed in the portal venous system by an interposed extracorporeal device. Each treatment lasted 6 h. The survival was assessed at 5 days after L.E.O2 NARDO treatment or sham operation. In both groups blood samples were collected for biochemical analysis at different time points and liver biopsies were collected 48 h after intoxication and at sacrifice. We observed decreased transaminases levels and a more rapid INR recovery in the study group, as compared to the control group. Eight animals of the study group vs. two animals of the control group survived at five days after surgery with a statistically significant difference (p<0.05). Liver biopsies performed at sacrifice showed a reduction of the damaged hepatic areas in the study group as compared to the control group. Arterial blood supply in the portal system through the L.E.O2 NARDO device is easily applicable, efficacious, and safe in a swine model of AHF induced by CCl4 intoxication.


Upcycling to Sustainably Reuse Plastics.
Plastics are now indispensable in daily lives. However, the pollution from plastics is also increasingly becoming a serious environmental issue. Recent years have seen more sustainable approaches and technologies, commonly known as upcycling, to transform plastics into value-added materials and chemical feedstocks. In this review, the latest research on upcycling is presented, with a greater focus on the use of renewable energy as well as the more selective methods to repurpose synthetic polymers. First, thermal upcycling approaches are briefly introduced, including the redeployment of plastics for construction uses, 3D printing precursors, and lightweight materials. Then, some of the latest novel strategies to deconstruct condensation polymers to monomers for repolymerization or introduce vulnerable linkers to make the plastics more degradable are discussed. Subsequently, the review will explore the breakthroughs in plastics upcycling by heterogeneous and homogeneous photocatalysis, as well as electrocatalysis, which transform plastics into more versatile fine chemicals and materials while simultaneously mitigating global climate change. In addition, some of the biotechnological advances in the discovery and engineering of microbes that can decompose plastics are also presented. Finally, the current challenges and outlook for future plastics upcycling are discussed to stimulate global cooperation in this field.


Boiling histotripsy lesion characterization on a clinical magnetic resonance imaging-guided high intensity focused ultrasound system.
High intensity focused ultrasound (HIFU) is a non-invasive therapeutic technique that can thermally ablate tumors. Boiling histotripsy (BH) is a HIFU approach that can emulsify tissue in a few milliseconds. Lesion volume and temperature effects for different BH sonication parameters are currently not well characterized. In this work, lesion volume, temperature distribution, and area of lethal thermal dose were characterized for varying BH sonication parameters in tissue-mimicking phantoms (TMP) and demonstrated in ex vivo tissues. The following BH sonication parameters were varied using a clinical MR-HIFU system (Sonalleve V2, Philips, Vantaa, Finland): acoustic power, number of cycles/pulse, total sonication time, and pulse repetition frequency (PRF). A 3×3×3 pattern was sonicated inside TMP's and ex vivo tissues. Post sonication, lesion volumes were quantified using 3D ultrasonography and temperature and thermal dose distributions were analyzed offline. Ex vivo tissues were sectioned and stained with H&E post sonication to assess tissue damage. Significant increase in lesion volume was observed while increasing the number of cycles/pulse and PRF. Other sonication parameters had no significant effect on lesion volume. Temperature full width at half maximum at the end of sonication increased significantly with all parameters except total sonication time. Positive correlation was also found between lethal thermal dose and lesion volume for all parameters except number of cycles/pulse. Gross pathology of ex vivo tissues post sonication displayed either completely or partially damaged tissue at the focal region. Surrounding tissues presented sharp boundaries, with little or no structural damage to adjacent critical structures such as bile duct and nerves. Our characterization of effects of HIFU sonication parameters on the resulting lesion demonstrates the ability to control lesion morphologic and thermal characteristics with a clinical MR-HIFU system in TMP's and ex vivo tissues. We demonstrate that this system can produce spatially precise lesions in both phantoms and ex vivo tissues. The results provide guidance on a preliminary set of BH sonication parameters for this system, with a potential to facilitate BH translation to the clinic.


Radiation oncology: physics advances that minimize morbidity.
Radiation therapy has become an ever more successful treatment for many cancer patients. This is due in large part from advances in physics including the expanded use of imaging protocols combined with ever more precise therapy devices such as linear and particle beam accelerators, all contributing to treatments with far fewer side effects. This paper will review current state-of-the-art physics maneuvers that minimize morbidity, such as intensity-modulated radiation therapy, volummetric arc therapy, image-guided radiation, radiosurgery and particle beam treatment. We will also highlight future physics enhancements on the horizon such as MRI during treatment and intensity-modulated hadron therapy, all with the continued goal of improved clinical outcomes.


A Light Responsive Nanoparticle-Based Delivery System Using Pheophorbide A Graft Polyethylenimine for Dendritic Cell-Based Cancer Immunotherapy.
In this study, the photochemical internalization (PCI) technique was adopted in a nanoparticle-based antigen delivery system to enhance antigen-specific CD8+ T cell immune response for cancer immunotherapy. Pheophorbide A, a hydrophobic photosensitizer, grafted with polyethylenimine (PheoA-PEI) with endosome escape activity and near-infrared imaging capability was prepared. A model antigen ovalbumin (OVA) was then complexed with PheoA-PEI to form PheoA-PEI/OVA nanoparticles (PheoA-PEI/OVA NPs) that are responsive to light. Flow cytometry analysis revealed increased endocytosis in a murine dendritic cell line (DC2.4) that was treated with PheoA-PEI/OVA NPs compared to free OVA. Generation of reactive oxygen species (ROS) in DC2.4 cells was also confirmed quantitatively and qualitatively using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Confocal laser scanning microscopy (CLSM) further demonstrated that the PheoA-PEI/OVA NPs enhanced cytosolic antigen release after light stimulation. Moreover, PheoA-PEI/OVA NP treated DC2.4 cells exhibited enhanced cross-presentation to B3Z T cell hybridoma in vitro after light irradiation, substantially increased compared to those treated with free OVA. Consistently, in vivo results revealed upregulation of CD3+CD8+T lymphocytes in tumors of mice treated with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. The activated T cell response is partly responsible for the inhibitory effect on E.G7 tumor growth in mice immunized with dendritic cells plus PheoA-PEI/OVA NPs and light irradiation. Our results demonstrate the feasibility to enhance antigen-specific CD8+ T cell immune response by light-responsive nanoparticle-based vaccine delivery for cancer immunotherapy.


Potassium homeostasis and dyskalemias: the respective roles of renal, extrarenal, and gut sensors in potassium handling.
Integrated mechanisms controlling the maintenance of potassium homeostasis are well established and are defined by the classic "feedback control" of potassium balance. Recently, increasing investigative attention has focused on novel physiological paradigms that increase the complexity and precision of homeostasis. This review briefly considers the classic and well-established feedback control of potassium and then considers subsequent investigations that inform on an intriguing and not widely recognized complementary paradigm: the "feed-forward control of potassium balance." Feed-forward control refers to a pathway in a homeostatic system that responds to a signal in the environment in a predetermined manner, without responding to how the system subsequently reacts (i.e., without responding to feedback). Studies in several animal species, and recently in humans, have confirmed the presence of a feed-forward control mechanism that is capable of mediating potassium excretion independent of changes in serum potassium concentration and aldosterone. Knowledge imparted by this update of potassium homeostasis hopefully will facilitate the clinical management of hyperkalemia in patients with chronic and recurrent hyperkalemia. Awareness of this updated integrative control mechanism for potassium homeostasis is more relevant today when the medical community is increasingly focused on leveraging and expanding established renin-angiotensin-aldosterone system inhibitor treatment regimens and on successfully coping with the challenges of managing hyperkalemia provoked by renin-angiotensin-aldosterone system inhibitors. These new insights are relevant to the future design of clinical trials delineating renal potassium handling.


Activation of Gq/11 in the mouse corpus luteum is required for parturition.
Mice with a deletion of Gα(q/11) in granulosa cells were previously shown to be subfertile. They also have a reduced ovulatory response due to a deficiency in the ability of the activated LH receptor to fully induce the granulosa cell progesterone receptor. Because this conditional deletion of Gα(q/11) will interfere with the actions of any G protein-coupled receptor that activates G(q/11) in granulosa or luteal cells, we sought to determine whether the actions of other hormones that contribute to fertility were also impaired. We focused our attention on prostaglandin F2 (PGF2)α, because this hormone is known to activate phospholipase C (a prominent Gα(q/11) effector) in luteal cells and because the action of PGF2α on luteal cells is the first step in the murine parturition pathway. Our data show that the conditional deletion of Gα(q/11) from granulosa cells prevents the ability of PGF2α to induce Akr1c18 in luteal cells. Akr1c18 codes for 20α-hydroxysteroid dehydrogenase, an enzyme that inactivates progesterone. The PGF2α-mediated induction of this enzyme towards the end of pregnancy increases the inactivation of progesterone and precipitates parturition in mice. Thus, the conditional deletion of Gαq/11 from granulosa/luteal cells prevents the progesterone withdrawal that occurs at the end of pregnancy and impairs parturition. This novel molecular defect contributes to the subfertile phenotype of the mice with a deletion of Gα(q/11) from granulosa cells.


[Multi-family therapy in day care settings].
This article describes the practice of multi-family therapy in day care settings. Between six to eight families attend together for whole days and weeks and the principles and the methods of this approach are described and illustrated with examples of systemic work with children with severe behavioural and learning disorders, as well as with adolescents presenting with anorexia nervosa.


FISH localization of the human Y-homolog of protein kinase PRKX (PRKY) to Yp11.2 and two pseudogenes to 15q26 and Xq12-->q13.
Recently, we reported the isolation of a new subfamily of serine-threonine protein kinases. This subfamily was shown to consist of at least four members. Sequencing and FISH mapping of all 4 members now reveals that the Y-homolog (PRKY) of the previously mapped PRKX gene (Xp22.3) is located in Yp11.2, in close vicinity to AMELY. The other two copies reside on Xq12-->q13 (PRKXP2) and 15q26 (PRKXP1, containing CA repeat STS D15S87) and represent pseudogenes.


Cutaneous lesions caused by the yellow fever vaccine - have you ever seen them?
The Yellow Fever virus was isolated in 1927 and the disease is considered endemic and epidemic in tropical regions of South America and Africa, with thousands of new cases reported annually. Several side effects of the vaccine have already been reported. Although reports of skin rash secondary to the vaccine range from 0 to 15%, no image or detailed description of the lesions were found in the literature. Here we describe a rash on a toddler vaccinated to travel.


Laser-induced silver nanojoining of gold nanoparticles.
Gold nanoparticles have been silver-joined to fabricate nanowires by irradiating gold nanospheres of 25 nm in diameter and silver nanospheres of 8 nm in diameter held together on a carbon-coated copper grid with a 30 ps laser pulse of 532 nm for 20 min at a fluence of 3.0 mJ/cm2. Laser-induced nanojoining of silver nanoparticles as well as that of gold nanoparticles has also been carried out by varying the wavelength and fluence of irradiation laser pulses. Irradiation at an optimum condition of laser fluence is essential for the proper silver nanojoining of gold nanospheres to produce gold@silver core-shell composite nanowires. The excitation of the surface plasmon resonances of the base-metallic gold nanospheres rather than the filler-metallic silver nanospheres paves the way for the silver nanojoining of gold nanoparticles.


Cocaethylene: When Cocaine and Alcohol Are Taken Together.
Cocaine is taken frequently together with ethanol and this combination produces a psychoactive metabolite called cocaethylene which has similar properties to the parent drug and may be more cardiotoxic. Cocaethylene has a longer half-life than cocaine, so that people who combine cocaine and ethanol may experience a longer-lasting, as well as more intense, psychoactive effect. Cocaethylene is the only known instance where a new psychoactive substance is formed entirely within the body. Although known to science for decades, cocaethylene has not been extensively studied and even its metabolic pathways are not entirely elucidated. Like its parent drug, cocaethylene blocks the reuptake of dopamine and increases post-synaptic neuronal activity; the parent drug may also block reuptake of serotonin as well. Cocaethylene has been studied in animal models in terms of its pharmacology and its potential neurological effects. Since the combination of cocaine and alcohol is commonly used, it is important for clinicians to be aware of cocaethylene, its role in prolonging or intensifying cocaine intoxication, and how it may exacerbate cocaine-induced cardiovascular disorders. Most cardiac-related risk assessment tools do not ask about cocaine use, which can prevent clinicians from making optimal therapeutic choices. Greater awareness of cocaethylene is needed for clinicians, and those who use cocaine should also be aware of the potential for polysubstance use of cocaine and ethanol to produce a potentially potent and long-lasting psychoactive metabolite.


Molecular alterations and potential actionable mutations in peritoneal mesothelioma: a scoping review of high-throughput sequencing studies.
Peritoneal mesothelioma (PeM) is a rare malignancy with a poor prognosis. Currently there is a lack of effective systemic therapies. Due to the rarity of PeM, it is challenging to study new treatment options. Off-label use of targeted drugs could be an effective approach. This scoping review aims to explore the genomic landscape of PeM to identify potential therapeutic targets. A systematic literature search of Embase, Medline, Web of Science, the Cochrane Library, and Google Scholar was carried out up to 1 November 2022. Studies that reported on molecular alterations in PeM detected by high-throughput sequencing techniques were included. Genes that were altered in ≥1% of PeMs were selected for the identification of potential targeted therapies. Thirteen articles were included, comprising 824 PeM patients. In total, 142 genes were altered in ≥1% of patients, of which 7 genes were altered in ≥10%. BAP1 was the most commonly altered gene (50%). Other commonly altered genes were NF2 (25%), CDKN2A (23%), CDKN2B (17%), PBRM1 (15%), TP53 (14%), and SETD2 (13%). In total, 17% of PeM patients were carriers of a germline mutation, mainly in BAP1 (7%). This scoping review provides an overview of the mutational landscape of PeM. Germline mutations might be a larger contributor to the incidence of PeM than previously thought. Currently available targeted therapy options are limited, but several targeted agents [such as poly (ADP-ribose) polymerase (PARP), enhancer of zeste homolog 2 (EZH2), and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors] were identified that might provide new targeted therapy options in the future.


The Effect of Transformational and Transactional Leadership Styles on Organizational Readiness for Change Among Health Professionals.
The purpose of this study was to determine the effect of transformational and transactional leadership styles on organizational readiness for change among health professionals in the case of selected public hospitals in the North Showa Zone, Oromia Region, Ethiopia. The institutional-based cross-sectional study design was employed for one month in April 2021. The data were collected from a sample of 212 subordinate health professional staffs. Multi-factor leadership surveys and organizational readiness for change questionnaires were used for data collection. Data were analyzed using descriptive statistics and exploratory factor analysis, run on the SPSS 23 version. Pearson correlation and multiple regressions were used. Multiple regression results were expressed using the statistical values R2 and β-coefficient. Statistical significance was declared at a P-value of <.05. The Pearson product correlation of organizational readiness for change was found to be low positive and statistically significant for both transformational leadership behavior (r = .49, P < .01) and transactional leadership behavior (r = .39, P < .01). Both transformational leadership behavior (t = 5.32, P = .00) and transactional leadership behavior (t = 2.08, P = .034) were found to be significant contributors to the variance of organizational readiness for change among health professionals, according to the findings. However, transformational leadership behavior style appears to make a more significant contribution (β = 0.39) than transactional leadership style (β = 0.15) in predicting organizational readiness for change among health professionals. The study revealed that whenever transformational and/or transactional leadership behaviors are exhibited by the administrative staff, readiness for organizational change (commitment and efficacy) increases among health professionals. The study also concluded that a quarter of the readiness for organizational change can be affected by the two leadership styles.


Clinical evaluation of a functional prothrombin time-based assay for identification of factor V Leiden carriers in a group of Italian patients with venous thrombosis.
The efficiency of a new prothrombin-based activated protein C (APC) resistance test to detect factor V Leiden (FVL) was clinically evaluated in 150 Italian patients with deep venous thrombosis. Patient samples are diluted in factor-V-deficient plasma, an APC-containing reagent, and specific factor V activator; after incubation, clotting is initiated by addition of activated-factor-FV-dependent prothrombin activator. Two prothrombin time determinations were performed under identical assay conditions except that no APC was added to one. A ratio over 4.2 for normal individuals and under 2.0 for FVL patients is expected: between 1.3 and 1.9 for FVL heterozygotes, and between 1.0 and 1.1 for FVL homozygotes. Using a predefined cut-off ratio of 2.0, a specificity and a sensitivity of 1.00 for detection of FVL mutation were found. With a cut-off ratio of 1.1, a specificity of 0.98 and a sensitivity of 1.00 were found for discrimination between FVL heterozygous (n = 60) and homozygous (n = 6). No interferences by heparins, oral contraceptives, oral anticoagulant therapy, protein C, protein S, D-dimer, homocysteine, MTHFR mutations and antiphospholipid autoantibodies were detected. In our experience, this new prothrombin time-based APC resistance assay provides improved discrimination between normal individuals and FVL carriers compared with the classical methods. Moreover, this new assay allows good discrimination between homozygous and heterozygous FVL carriers. In the authors' experience this prothrombin time-based method was not influenced by many factors compared with the classical activated partial thromboplastin time-based method.


A red algal cyclophilin has an effect on development and growth in Nicotiana tabacum.
In this study, an algal Cyp was introduced into plant to research the effect of the gene on growth and development. cDNA GjCyp-1 was isolated from the red alga (Griffithsia japonica), and a recombinant GjCyp-1 containing a CaMV35S promoter at the amino-terminus was constructed in Nicotiana tabacum. The altered GjCyp-1 levels in plants and the expression pattern of Cyp after hormone treatment were confirmed by RNA blotting. Transcript of GjCyp-1 was induced by plant hormones such as gibberellic acid (GA(3)), indoleacetic acid (IAA), and zeatin (ZA). Constitutive overexpression of GjCyp-1 appeared to be beneficial to seed germination. The ratio of emergence of cotyledon from seeds overexpressing GjCyp-1 was almost three times higher than that of the transgenic seeds carrying only the vector. In addition, it was found that most of the seedlings overexpressing GjCyp-1 were dwarfs with altered root systems. The ratio of leaf length and width and root length from transgenic seedlings overexpressing GjCyp-1 was almost 2 and 3.5 times lower than that of the transgenic seedlings carrying only the vector, respectively. The data in this study suggest that GjCyp-1 may affect development and growth in organisms.


Bridging the gap: Palliative care integration into survivorship care.
As the number of cancer survivors grows, there is an increasing need for comprehensive care to address the unique physical, psychological, and social needs of this population. Palliative care (PC) integration within survivorship care offers a promising model of care, however, there is no comprehensive review of literature to guide clinical practice. This manuscript presents a scoping review of the research literature on models of care that integrate PC with survivorship care, as well as a detailed description of an exemplar clinical model. We identified 20 articles that described various models of survivorship care with integrated PC, highlighting the diversity of approaches and the multidisciplinary nature of interventions. Few studies reported outcomes but those that did demonstrated improvements in pain, self-efficacy, depression, function, and documentation of advance care planning. The evidence base remains limited, indicating the need for further research in this area with a focus on exploring outcomes using prospective experimental designs. Future clinical practice and research should explore sustainable payment models and the implementation of integrated survivorship care in value-based payment systems.


Human leptin levels are pulsatile and inversely related to pituitary-adrenal function.
Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese.


Conditions of visual verbal extinction: does the ipsilesional stimulus have to be identified?
Six left-neglect patients were presented with four-letter words in the left and/or right hemifield, in different contextual conditions: unilateral, bilateral-x in which one word appears on one side and a string of "x" appears on the other side (the side of "x'' was not predictable), and bilateral-word (presentation of one word in each hemifield). In Experiment 1, left extinction occurred even if the right stimulus was an easily discriminable string of "x." Experiment 2 showed that increasing the size of the left stimuli reduced extinction when a string of "x" was presented on the right hemifield. However, extinction was stronger with bilateral-word presentation. These results indicate the presence of an early component in the extinction phenomenon, i.e., a "magnetic" attraction toward the ipsilesional hemifield, but are also in favor of some additional deficit, at a later stage of information processing.


Computational design of synthetic gene circuits with composable parts.
In principle, novel genetic circuits can be engineered using standard parts with well-understood functionalities. However, no model based on the simple composition of these parts has become a standard, mainly because it is difficult to define signal exchanges between biological units as unambiguously as in electrical engineering. Corresponding concepts and computational tools for easy circuit design in biology are missing. Taking inspiration from (and slightly modifying) ideas in the 'MIT Registry of Standard Biological Parts', we developed a method for the design of genetic circuits with composable parts. Gene expression requires four kinds of signal carriers: RNA polymerases, ribosomes, transcription factors and environmental 'messages' (inducers or corepressors). The flux of each of these types of molecules is a quantifiable biological signal exchanged between parts. Here, each part is modeled independently by the ordinary differential equations (ODE) formalism and integrated into the software ProMoT (Process Modeling Tool). In this way, we realized a 'drag and drop' tool, where genetic circuits are built just by placing biological parts on a canvas and by connecting them through 'wires' that enable flow of signal carriers, as it happens in electrical engineering. Our simulations of well-known synthetic circuits agree well with published computational and experimental results. The code is available on request from the authors.


[Patient satisfaction in 4 hospitals of the Basque Health Service].
To compare patient satisfaction in 4 acute hospitals. The sample was composed of individuals admitted to 4 hospitals in the Basque Health Service (Osakidetza, Spain) in January and February 2002. Six hundred and fifty patients were selected from each hospital and were sent a satisfaction questionnaire composed of 34 items summarized in 6 factors. Independent scores for each factor were created. Sociodemographic variables, those related to admission, as well as some global questions and the average scores of the factors were compared among the 4 hospitals. Differences between the 4 hospitals were found in age, the number of previous admissions, type of service, length of hospital stay, and the questions evaluating satisfaction with waiting time between users' arrival at the hospital and admission. Although the degree of satisfaction was high, differences were detected depending on the factor and the hospital. Thus, "information", "dealings with staff" and "comfort" were rated more highly by users of hospital 3 than by those of hospital 1. The results observed in the univariate analysis changed only slightly in the multivariate models. The questionnaire used allowed comparable results to be obtained among the 4 hospitals participating in this study and identified areas of excellence and areas requiring improvement in each of the centers.


Top-cited articles in traumatic brain injury.
A review of the top-cited articles in a scientific discipline can identify areas of research that are well established and those in need of further development, and may, as a result, inform and direct future research efforts. Our objective was to identify and characterize the top-cited articles in traumatic brain injury (TBI). We used publically available software to identify the 50 TBI articles with the most lifetime citations, and the 50 TBI articles with the highest annual citation rates. A total of 73 articles were included in this review, with 27 of the 50 papers with the highest annual citation rates common to the cohort of 50 articles with the most lifetime citations. All papers were categorized by their primary topic or focus, namely: predictor of outcome, pathology/natural history, treatment, guidelines and consensus statements, epidemiology, assessment measures, or experimental model of TBI. The mean year of publication of the articles with the most lifetime citations and highest annual citation rates was 1990 ± 14.9 years and 2003 ± 6.7 years, respectively. The 50 articles with the most lifetime citations typically studied predictors of outcome (34.0%, 17/50) and were specific to severe TBI (38.0%, 19/50). In contrast, the most common subject of papers with the highest annual citation rates was treatment of brain injury (22.0%, 11/50), and these papers most frequently investigated mild TBI (36.0%, 18/50). These findings suggest an intensified focus on mild TBI, which is perhaps a response to the dedicated attention these injuries are currently receiving in the context of sports and war, and because of their increasing incidence in developing nations. Our findings also indicate increased focus on treatment of TBI, possibly due to the limited efficacy of current interventions for brain injury. This review provides a cross-sectional summary of some of the most influential articles in TBI, and a bibliometric examination of the current status of TBI research.


Serum biochemical profile, enzymatic activity and lipid peroxidation in organs of laying hens fed diets containing cashew nut shell liquid.
The objective of this study was to evaluate the effect of feeding laying hens diets containing cashew nut shell liquid (CNSL) as a source of anacardic acid on the blood biochemical parameters as well as the enzymatic activity and lipid peroxidation of liver and tissues of the reproductive system (ovary, magnum, and uterus). A total of 216 Hisex White commercial laying hens were distributed randomly into six treatments, with six replicates of six birds. Treatments consisted of a diet without growth promoter (GP); a diet with GP; and diets without GP, with addition of increasing levels of CNSL (0.25, 0.50, 0.75 and 1.0%). Addition of CNSL to the diet did not affect the blood biochemical parameters (uric acid, creatinine, alanine aminotransferase, aspartate aminotransferase, total cholesterol, high density lipoproteins, low-density lipoproteins and triglycerides), the enzymatic activity (superoxide dismutase and nonprotein sulphydryl groups) in the organs (liver, ovary, magnum and uterus) or the peroxidation of lipids from the blood serum, liver, magnum and uterus (p > 0.05). However, the addition of 0.75% and 1.00% CNSL provided a lower thiobarbituric acid reactive substances content in the birds' ovary (p < 0.001) compared to birds of other treatments, whereas the treatment without the GP provided a higher value. Addition of up to 1% of the CNSL as a source of anacardic acid in the laying hens' diets does not influence blood biochemical parameters or the endogenous enzymatic activity in the liver, ovary, magnum and uterus, but affects the lipid peroxidation in the ovary, although the problem is reduced from the inclusion of 0.75% CNSL.


Efficacy of different selective media for the isolation of salmonellae from faeces.
Comparative results obtained in isolating salmonellae from faeces by the use of tetrathionate broth, MS, and MM enrichment medium are given. The best results were obtained by tetrathionate broth prepared from infusion broth. The MS as well as the MM medium increased the total number of positive results.


A transgenic mouse model for studying the clearance of blood-borne pathogens via human complement receptor 1 (CR1).
Complement receptor 1 (CR1) on the surface of human erythrocytes facilitates intravascular clearance of complement-opsonized pathogens. The need for complement activation can be circumvented by directly coupling the organism to CR1 using a bispecific monoclonal antibody heteropolymer (HP). Lack of a functional homologue to CR1 on mouse erythrocytes has made it difficult to study HP-dependent clearance of pathogens in small animals. We have developed a transgenic mouse that expresses human CR1 on erythrocytes. CR1 antigen is of appropriate size and in a clustered distribution as confirmed by immunoblotting and fluorescence microscopy, respectively. HP that immobilized bacteriophage PhiX174 prototype pathogen to erythrocyte CR1 of the transgenic mice increased the rate of clearance of the virus compared with HP that bound bacteriophage, but not CR1. This transgenic mouse model will allow evaluation of different HPs for their in vivo efficacy and potential as human therapeutics.


Vertical transmission of microcystins to Nile crocodile (Crocodylus niloticus) eggs.
Cyanobacteria or blue green algae are known for their extensive and highly visible blooms in eutrophic, stagnant freshwater bodies. Climate change and global warming have also contributed to a rise in toxic cyanobacterial blooms. One of the most important cyanobacteria is Microcystis aeruginosa, which can synthesize various microcystins that can affect the health of terrestrial and aquatic animals. Commercial Nile crocodile (Crocodylus niloticus) farming in South Africa is based on keeping breeders (adult males and females) in big dams on farms (captive-bred approach). Unfortunately, cyanobacterial blooms in the breeder dams are a concern to farm owners, managers and veterinarians. The main objectives of this research project were to determine if microcystins were present in the contents of crocodile eggs and the liver and yolk of dead hatchlings, and to determine if the reduced hatchability on commercial farms might be caused by these toxins. Furthermore, the concentration of microcystins in the breeder dam was monitored on a monthly basis spanning the ovulation and egg laying period. During the hatching season microcystin concentrations in unfertilised eggs, egg shell membranes and in the yolk and liver of dead hatchlings were determined using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Microcystins were detected in Nile crocodile egg and hatchling samples. Microcystin (MC-LR, MC-RR, MC-YR) concentrations in the crocodile egg and hatchling samples collected from clutches with a good hatching rate (≥90%) ranged between 0 and 1.76 ng g-1, with the highest concentration in the egg shell membranes. Microcystin concentrations in samples collected from clutches with a bad hatching rate (≤10%) ranged from 0 - 1.63 ng g-1 with the highest concentration detected in the hatchling yolk. However, the concentrations were probably underestimated as the percentage recovery from spiked samples was very low with the extraction method employed. Bayesian analysis suggests that the liver, yolk and unfertilised egg all have similar microcystin concentrations, while the membranes have (with moderate to high certainty) higher microcystin concentrations. There appears to be no difference in microcystin concentrations among good and bad clutches across all tissue types or within a specific tissue type, but due to the small sample size, it was not possible to determine whether microcystin affected the hatchability of Nile crocodile eggs. However, vertical transmission of microcystin variants to the Nile crocodile egg does occur and the possible implications for the survival of wild Nile crocodile populations should be ascertained.


Infective endocarditis of an asymptomatic congenital aorta-right atrial tunnel: a case report.
Aorta-right atrial tunnel (ARAT) is a rare congenital anomaly whose aetiology and incidence are unknown. It might represent a diagnostic and therapeutic challenge requiring a combination of imaging modalities and an integrated teamwork. We report a case of a 23-year-old man with an asymptomatic ARAT complicated by infective endocarditis, diagnosed with non-invasive multimodality imaging, and successfully treated with a catheter-based approach. Aorta-right atrial tunnel closure in asymptomatic patients is still a matter of debate. Considering the risk of serious complications surgical treatment might be recommended soon after diagnosis. In selected cases, catheter-based closure might represent a safe, effective, and less invasive alternative to traditional surgical approach.


Volume overload and its risk factors in South African chronic kidney disease patients: an appraisal of bioimpedance spectroscopy and inferior vena cava measurements.
Fluid retention occurs early in chronic kidney disease (CKD) resulting in increased cardiovascular morbidity and mortality. This study aimed to assess volume and nutritional status among South African CKD participants and determine the relationship between malnutrition, inflammation, atherosclerosis, and volume overload using a body composition monitor (BCM). We also evaluated the usefulness of BCM measurement in assessing volume overload. 160 participants comprising hemodialysis, peritoneal dialysis, stage 3 CKD patients, and healthy controls (40 in each group) were studied. A BCM was used to assess fluid and nutritional status. Cardiac dimension measurements, and inferior vena cava diameter (IVCD) and carotid intima media thickness were assessed by echocardiography and ultrasonography, respectively. Serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels were measured as markers of inflammation. Fluid overload and malnutrition were present in 68% and 63% of studied patients, respectively. Using physical examination findings as the reference measurements for volume overload, the area under the concentration curves for BCM and IVCD measurements were 0.866 (sensitivity 82%, specificity 74%, p < 0.001) and 0.727 (sensitivity 57%, specificity 70%, p < 0.001), respectively. Lean tissue index, inflammation, and atherosclerosis were associated with volume overload. Volume overload and malnutrition were common across the spectrum of South African CKD cohorts; volume overload was associated with malnutrition, inflammation, and atherosclerosis. Bioimpedance spectroscopy (BIS) is a useful and sensitive tool for the assessment of fluid status in clinically euvolumic nondialytic CKD patients.


Aspects of skeletal muscle modelling.
The modelling of skeletal muscle raises a number of philosophical questions, particularly in the realm of the relationship between different possible levels of representation and explanation. After a brief incursion into this area, a list of desiderata is proposed as a guiding principle for the construction of a viable model, including: comprehensiveness, soundness, experimental consistency, predictive ability and refinability. Each of these principles is illustrated by means of simple examples. The presence of internal constraints, such as incompressibility, may lead to counterintuitive results. A one-panel example is exploited to advocate the use of the principle of virtual work as the ideal tool to deal with these situations. The question of stability in the descending limb of the force-length relation is addressed and a purely mechanical analogue is suggested. New experimental results confirm the assumption that fibre stiffness is positive even in the descending limb. The indeterminacy of the force-sharing problem is traditionally resolved by optimizing a, presumably, physically meaningful target function. After presenting some new results in this area, based on a separation theorem, it is suggested that a more fundamental approach to the problem is the abandoning of optimization criteria in favour of an explicit implementation of activation criteria.


Impact of biofluid viscosity on size and sedimentation efficiency of the isolated microvesicles.
Microvesicles are nano-sized lipid vesicles released by all cells in vivo and in vitro. They are released physiologically under normal conditions but their rate of release is higher under pathological conditions such as tumors. Once released they end up in the systemic circulation and have been found and characterized in all biofluids such as plasma, serum, cerebrospinal fluid, breast milk, ascites, and urine. Microvesicles represent the status of the donor cell they are released from and they are currently under intense investigation as a potential source for disease biomarkers. Currently, the "gold standard" for isolating microvesicles is ultracentrifugation, although alternative techniques such as affinity purification have been explored. Viscosity is the resistance of a fluid to a deforming force by either shear or tensile stress. The different chemical and molecular compositions of biofluids have an effect on its viscosity and this could affect movements of the particles inside the fluid. In this manuscript we addressed the issue of whether viscosity has an effect on sedimentation efficiency of microvesicles using ultracentrifugation. We used different biofluids and spiked them with polystyrene beads and assessed their recovery using the Nanoparticle Tracking Analysis. We demonstrate that MVs recovery inversely correlates with viscosity and as a result, sample dilutions should be considered prior to ultracentrifugation when processing any biofluids.


Chronic carbon monoxide poisoning: effects on performance of the isolated right ventricle.
Rats were exposed continuously for 21-35 days to 500 ppm carbon monoxide (37.4-39.2% HbCO). Aerobic resting force (RF)-active isometric twitch force (AF) curves of isolated right ventricle preparations were constructed at 27 degrees C. CO and control groups are nearly identical when expressed as percent of maximal AF over the range of RF used. There are no significant differences in AF either at the peak of the curve or at RF = 1 g. During 15 min of anoxia AF declines at both RF's used. Increased anoxic tolerance is apparent in all CO preparations when anoxic AF is plotted as percent of preanoxic AF. The effect is most marked at RF = 1 g, where time to one-half preanoxic AF is 12.6 +/- 0.9 vs.9.3 +/- 0.8 min for CO-exposed and controls, respectively. However, no significant differences in "absolute" AF are seen between the groups at either level of RF at any minute during anoxia. Aerobic recovery of CO preparations is markedly enhanced at 1 g RF. Anoxic tolerance and aerobic recovery differences, however, are smaller at the peak of the RF-AF curve. Effects on time to peak AF and maximal rate of rise of AF are not marked at either level of RF in CO preparations.


Infective endocarditis: a history of the development of its understanding.
Inflammation of the inner layer of the heart, especially the valvular endothelium, chordae tendinae and mural endocardium was first recognized almost 350 years ago. Over the years it has had many names, but is now generally designated infective endocarditis (IE) and has an associated infectious agent. A sterile vegetative process can also affect the valves and is usually referred to as Libman-Sacks endocarditis. The developments of medical science that allowed for our understanding of this entity included refinement of the autopsy, medical microscopy, microbiology, and in recent years, molecular studies. Some observations were misleading but clarification particularly followed the reports of Morgagni, Osler and Libman. As understanding of the pathobiology of infective endocarditis grew so did the effectiveness of therapy. This paper provides a detailed history of the development of the concept of Infective endocarditis citing many key morphological observations and concludes with brief comments about current concepts of pathogenesis as well as a few remarks about therapy.


Activation of FcRn Mediates a Primary Resistance Response to Sorafenib in Hepatocellular Carcinoma by Single-Cell RNA Sequencing.
Sorafenib is the first-line therapeutic option for advanced hepatocellular carcinoma (HCC). Many patients exhibit a primary resistance (PR) response after initial treatment. In previous studies, compared to acquired resistance, the mechanism of PR is unclear. The present study aimed to evaluate the response of patient samples to sorafenib by patient-derived xenograft (PDX) models, and the differences at the transcriptome level between the sorafenib PR group and the sorafenib sensitive group were analyzed by single-cell sequencing technology. A specific cell cluster may be differentiated by the liver bud hepatic cells, and the JUN transcription factors in this cell cluster were highly activated. The albumin is secreted by other cell clusters, and the cluster stimulates the FcRn complex receptor to activate the HIF pathway and cell proliferation, resulting in a poor response to sorafenib. These findings are validated by both cell communication analysis and experiments. Thus, the current studies provided a novel approach for the treatment of sorafenib-resistant HCC.


Dark chocolate for children's blood pressure: randomised trial.
Higher adult blood pressure, even without hypertension, predicts cardiovascular outcomes, and is predicted by childhood blood pressure. Regular dark chocolate intake lowers blood pressure in adults, but effects in children are unknown. To examine the feasibility of school-based provision of dark chocolate and its short-term efficacy in reducing mean group blood pressure. 194 children (aged 10-12 years) were randomised by class to intervention (7 g dark chocolate daily for 7 weeks, n=124) or control (n=70) groups; 98% and 93% provided baseline and follow-up measurements, respectively. Intervention and control students had similar systolic (mean difference 1.7 mm Hg, 95% CI -0.6 to 4.1) and diastolic (-1.2 mm Hg, 95% CI -3.6 to 1.3) blood pressure, anthropometry and well-being at outcome. Results show that providing dark chocolate is feasible and acceptable in the school setting. For a definitive trial, the authors recommend a larger sample, endovascular function measures, and consideration of higher antioxidant 'dose' by virtue of duration and/or content.


Comparison of angiotensin-converting enzyme (ACE), neutral endopeptidase (NEP) and dual ACE/NEP inhibition on blood pressure and resistance arteries of deoxycorticosterone acetate-salt hypertensive rats.
Omapatrilat, an inhibitor of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE), is an effective antihypertensive agent. Here, we studied the relative roles of NEP and ACE inhibition and their effect on resistance artery structure and function of deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Omapatrilat (40 mg/kg per day), the NEP inhibitor CGS 25462 (CGS, 100 mg/kg per day) and the ACE inhibitor enalapril (10 mg/kg per day), were given for 3 weeks to DOCA-salt hypertensive rats. Effects on small mesenteric resistance arteries were studied on a pressurized myograph. Collagen deposition was evaluated by confocal microscopy. Systolic blood pressure of DOCA-salt rats was significantly reduced (P < 0.05) by omapatrilat and CGS. Omapatrilat and CGS treatment increased lumen diameter and decreased media width and media/lumen ratio of small arteries of DOCA-salt rats (P < 0.05). Small artery relaxation responses to acetylcholine improved under omapatrilat or CGS treatment. The stress-strain curve shifted leftward in mesenteric arteries from DOCA-salt rats compared to control rats. Omapatrilat or CGS treatment resulted in a rightward shift, which was significantly different from that induced by enalapril. Omapatrilat and CGS decreased collagen deposition in the vessel wall of DOCA-salt rats. Enalapril had no effect on blood pressure, vascular structure, endothelial function or collagen deposition in the vessel wall of DOCA-salt rats. Dual inhibition of ACE/NEP in DOCA-salt hypertensive rats resulted in potent anti-hypertensive effects, prevented vascular remodelling and improved endothelial function of resistance arteries. NEP inhibition is involved to a large extent in the effect of omapatrilat in DOCA-salt rats. These actions of omapatrilat may confer protection against end-organ damage characteristic of severe hypertension.


Floral Induction in Arabidopsis by FLOWERING LOCUS T Requires Direct Repression of BLADE-ON-PETIOLE Genes by the Homeodomain Protein PENNYWISE.
Flowers form on the flanks of the shoot apical meristem (SAM) in response to environmental and endogenous cues. In Arabidopsis (Arabidopsis thaliana), the photoperiodic pathway acts through FLOWERING LOCUS T (FT) to promote floral induction in response to day length. A complex between FT and the basic leucine-zipper transcription factor FD is proposed to form in the SAM, leading to activation of APETALA1 and LEAFY and thereby promoting floral meristem identity. We identified mutations that suppress FT function and recovered a new allele of the homeodomain transcription factor PENNYWISE (PNY). Genetic and molecular analyses showed that ectopic expression of BLADE-ON-PETIOLE1 (BOP1) and BOP2, which encode transcriptional coactivators, in the SAM during vegetative development, confers the late flowering of pny mutants. In wild-type plants, BOP1 and BOP2 are expressed in lateral organs close to boundaries of the SAM, whereas in pny mutants, their expression occurs in the SAM. This ectopic expression lowers FD mRNA levels, reducing responsiveness to FT and impairing activation of APETALA1 and LEAFY. We show that PNY binds to the promoters of BOP1 and BOP2, repressing their transcription. These results demonstrate a direct role for PNY in defining the spatial expression patterns of boundary genes and the significance of this process for floral induction by FT.


Effects of a large-scale social media advertising campaign on holiday travel and COVID-19 infections: a cluster randomized controlled trial.
During the Coronavirus Disease 2019 (COVID-19) epidemic, many health professionals used social media to promote preventative health behaviors. We conducted a randomized controlled trial of the effect of a Facebook advertising campaign consisting of short videos recorded by doctors and nurses to encourage users to stay at home for the Thanksgiving and Christmas holidays ( NCT04644328 and AEARCTR-0006821 ). We randomly assigned counties to high intensity (n = 410 (386) at Thanksgiving (Christmas)) or low intensity (n = 410 (381)). The intervention was delivered to a large fraction of Facebook subscribers in 75% and 25% of randomly assigned zip codes in high- and low-intensity counties, respectively. In total, 6,998 (6,716) zip codes were included, and 11,954,109 (23,302,290) users were reached at Thanksgiving (Christmas). The first two primary outcomes were holiday travel and fraction leaving home, both measured using mobile phone location data of Facebook users. Average distance traveled in high-intensity counties decreased by -0.993 percentage points (95% confidence interval (CI): -1.616, -0.371; P = 0.002) for the 3 days before each holiday compared to low-intensity counties. The fraction of people who left home on the holiday was not significantly affected (adjusted difference: 0.030; 95% CI: -0.361, 0.420; P = 0.881). The third primary outcome was COVID-19 infections recorded at the zip code level in the 2-week period starting 5 days after the holiday. Infections declined by 3.5% (adjusted 95% CI: -6.2%, -0.7%; P = 0.013) in intervention compared to control zip codes. Social media messages recorded by health professionals before the winter holidays in the United States led to a significant reduction in holiday travel and subsequent COVID-19 infections.


Aβ seeding potency peaks in the early stages of cerebral β-amyloidosis.
Little is known about the extent to which pathogenic factors drive the development of Alzheimer's disease (AD) at different stages of the long preclinical and clinical phases. Given that the aggregation of the β-amyloid peptide (Aβ) is an important factor in AD pathogenesis, we asked whether Aβ seeds from brain extracts of mice at different stages of amyloid deposition differ in their biological activity. Specifically, we assessed the effect of age on Aβ seeding activity in two mouse models of cerebral Aβ amyloidosis (APPPS1 and APP23) with different ages of onset and rates of progression of Aβ deposition. Brain extracts from these mice were serially diluted and inoculated into host mice. Strikingly, the seeding activity (seeding dose SD50) in extracts from donor mice of both models reached a plateau relatively early in the amyloidogenic process. When normalized to total brain Aβ, the resulting specific seeding activity sharply peaked at the initial phase of Aβ deposition, which in turn is characterized by a temporary several-fold increase in the Aβ42/Aβ40 ratio. At all stages, the specific seeding activity of the APPPS1 extract was higher compared to that of APP23 brain extract, consistent with a more important contribution of Aβ42 than Aβ40 to seed activity. Our findings indicate that the Aβ seeding potency is greatest early in the pathogenic cascade and diminishes as Aβ increasingly accumulates in brain. The present results provide experimental support for directing anti-Aβ therapeutics to the earliest stage of the pathogenic cascade, preferably before the onset of amyloid deposition.


Syphilis Maligna: A Presentation to Bear in Mind.
Malignant syphilis is an uncommon form of secondary syphilis associated with HIV infection. Clinically, it is characterized by necrotic nodules and generalized ulcerated lesions. We present 4 cases of malignant syphilis diagnosed after evaluating syphilis cases diagnosed at our hospital between 2012 and 2016. We describe the epidemiologic, clinical, histiopathologic, and serologic characteristics of malignant syphilis and explore its response to treatment and association with HIV infection. Although malignant syphilis is uncommon, there has been an increase in the number of cases published in recent years, particularly in young HIV-positive patients. Malignant syphilis must be contemplated in the differential diagnosis of HIV patients with ulcerated, necrotic lesions.


The effects of the addition of mechanical traction to physical therapy on low back pain? A systematic review with meta-analysis.
This study aimed to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) on the comparative effects of different types or parameters of lumbar traction in low back pain (LBP). CENTRAL, CINAHL, ISI Web of Science, PEDro, PubMed, and Scopus databases were searched from their inception to March 31, 2021. We considered all RCTs comparing different types or parameters of lumbar traction on adults who complained of LBP with or without lumbar radiculopathy (LR). Any restriction regarding publication time or language was applied. Two reviewers independently selected the studies, performed the quality assessment, and extracted the results. Meta-analysis employed a random-effects model. Sixteen studies met the inclusion criteria for qualitative analysis, and five were pooled. Meta-analyses of results from five studies on LBP with LR showed no significant difference between diverse tractions modalities at short-term follow-up. Very low to low-quality evidence supports these results. High-force and low-force traction demonstrated clinically significant improvements in pain. The literature suggests the short-term effectiveness of traction on pain in LBP with LR, regardless of the type or the dosage employed. Different effects of traction other the mechanical ones can be hypothesized. This systematic review may be relevant for clinical practice due to the similar effects of different traction types or dosages. Level I, Therapeutic Study.


Amifostine exerts anti-angiogenic activity and suppresses vascular endothelial growth factor secreted by hemopoietic stem/progenitor cells.
To assess, in vitro, the effect of Amifostine (AMF, WR-2721) on angiogenesis and levels of vascular endothelial growth factor (VEGF) secreted from hemopoietic stem/progenitor cell populations. We conducted the study in the research laboratories of the Hashemite University, Jordan between September 2003 and January 2005 where we took samples were from Myelodysplastic syndrome (MDS) patients and healthy donors attending Al-Hussein Cancer Center and We determined the proliferation of human umbilical vein endothelial cells (HUVECs) in cultures supplemented with media conditioned with AMF-treated and AMF-untreated pure hemopoietic cells [CD34+ cells, and erythroid, myeloid and megakaryocytic progenitors]. Furthermore, in the same conditioned media, we evaluated levels of elaborated VEGF by a sensitive enzyme linked immunosorbent assay. Biologically, media conditioned with AMF-treated cells reduced proliferation of HUVECs compared to media conditioned with untreated control cells (p<0.05). In cultures of AMF-untreated cells, elaboration of VEGF was higher (p<0.05) in media conditioned with cells from MDS patients compared to healthy donors. A 30 minutes pre-exposure of cells to AMF (500 mM) suppressed levels of VEGF secreted within 24 hours in 63 of 89 evaluated cultures. The percentage of reduction of VEGF in AMF-sensitive cultures was comparable in cultures of MDS cells (18%, 2-37%; median, range) and normal cells (12%, 2-45%). The results showed that AMF exerts an anti-angiogenic activity and suppresses the secretion of VEGF in hemopoietic stem/progenitor cells obtained from both healthy individuals and patients with MDS.