Development of Emu oil-loaded PCL/collagen bioactive nanofibers for proliferation and stemness preservation of human adipose-derived stem cells: possible application in regenerative medicine.
Adipose tissue-derived stem cells (ASCs) are promising candidate in stem cell therapies, and maintaining their stemness potential is vital to achieve effective treatment. Natural-based scaffolds have been recently attracted increasing attention in nanomedicine and drug delivery. In the present study, a polymeric nanofibrous scaffold was developed based on the polycaprolactone/Collagen (PCL/Coll) containing Emu oil as a bioactive material to induce the proliferation of ASCs, while simultaneously preserving the stemness property of those cells. Fabrication of the electrospun Emu oil-loaded PCL/Coll nanofibers was confirmed by using FE-SEM, FTIR, and tensile test. ASCs were seeded on two types of nanofibers (PCL/Coll and Emu oil-loaded PCL/Coll) and their proliferation, cell cycle progression, and stemness gene expressions were evaluated using MTT, propidium iodide staining, and qPCR during 14 days, respectively. The results indicated that ASCs displayed improved adhesion capacity with the higher rates of bioactivity and proliferation on the Emu oil-loaded nanofibers than the other groups. The proliferation capacity of ASCs on Emu oil-loaded PCL/Coll nanofibers was further confirmed by the cell cycle progression analysis. It was also found that Emu oil-loaded nanofibers significantly up-regulated the expression of stemness markers including sox-2, nanog, oct4, klf4, and c-Myc. The results demonstrated that the nanofibers containing Emu oil can reinforce the cell adhesion and enhance ASCs proliferation while preserving their stemness; therefore, using scaffolds containing natural products may have a great potential to enhance the in vitro expansion capacity of ASCs in the field of stem cell therapy and regenerative medicine.


Disseminated Intravascular Coagulation and Excessive Fibrinolysis (DIC XFL) Syndrome in Prostate Cancer: A Rare Complicated Disorder.
Disseminated Intravascular Coagulation (DIC) develops in patient with prostate cancer, which is manifested by systemic, intracranial, intracavitary or intracutaneous bleeding indicating uncompensated or excessive fibrinolysis (XFL). This case report is a description of a 61-year-old male with metastatic prostate cancer that progressed to manifest DIC. The condition is rare in clinical practice, and even rarer when is coupled with XFL. Treatment was mainly replenishing coagulation factors, platelets and controlling the disease progression with aggressive hormonal therapy. The patient progressed to coagulopathy further with fibrinolysis, hence leading to mortality. This case study discusses the pathophysiology of this complication and various methods to monitor the disease progression are discussed.


Associations between muscle mass, strength, and performance and non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is a rising global health issue. The influence of muscle in its pathophysiology has recently gained attention. Our aim was to investigate the association of low muscle mass, strength, and performance with the presence and severity of NAFLD. Patients with metabolic syndrome followed in an outpatient clinic, were consecutively included, between April 1st and December 31st, 2019. Abdominal ultrasound for the diagnosis of NAFLD, NAFLD fibrosis score (NFS) and Fibrosis-4 Index (FIB-4) for determination of significant fibrosis, dual-energy X-ray absorptiometry for calculation of skeletal muscle index (SMI = appendicular skeletal mass / weight x100) and sarcopenic index (SI = appendicular skeletal mass / Body Mass Index), and the Short Physical Performance Battery for muscle strength and performance assessment were performed. Sarcopenia was defined as low muscle strength and low SMI or SI. A total of 157 patients were included, of which 68.8% had NAFLD, 66.2% low SMI, 50.3% low SI, 16.6% low performance and 11.5% low strength. In patients with NAFLD, prevalence of significant fibrosis by NFS was 15.7%. Low SMI was associated with presence of NAFLD when adjusted for age, sex, type 2 diabetes mellitus, hypertension, and dyslipidemia, but not for body mass index and waist circumference. Low SMI, low SI, and sarcopenia were associated with significant fibrosis in univariate analysis; the small number of events precluded a multivariable analysis. Low SMI was associated with NAFLD independently of demographics and comorbidities but not of other parameters of body composition. This contrasts with most studies published on this matter.


Predictors of random sextant biopsy outcome in screened men with PSA > 4 ng/mL and a negative sextant biopsy at previous screening. Experience in a population-based screening program in Florence.
The aim of this study was to evaluate possible pedictors of the outcome of repeat random sextant biopsy of the prostate prompted by a rise in prostate-specific antigen (PSA). Random biopsies performed for PSA elevation (>4 ng/mL) in the course of a randomized study of screening efficacy were reviewed, and 87 consecutive biopsies (carcinoma = 13, high-grade prostatic intraepithelial neoplasia = 6, negative = 68) performed in subjects with a negative random biopsy at the previous screening round were considered. Findings at digital rectal examination or transrectal ultrasonography and total PSA value were not useful predictors of repeat biopsy outcome, whereas PSA velocity was significantly associated with biopsy outcome. The positive predictive value for a cancer biopsy was 2.7% (1/36), 28.5% (2/7), and 22.7% (10/44) for PSA velocity values of <0.1, 0.1-0.19, and >0.19 ng/mL/yr, respectively. A cutoff of 0.1 ng/mL/yr for PSA velocity would have allowed to avoid approximately half (35/74 = 47.2%) of the benign biopsies while decreasing the sensitivity by 7.6% (1/13), and is thus suggested as a possible criterion for the indication of repeat random biopsy for persistent PSA elevation.


Are we underestimating the diversity and incidence of insect bacterial symbionts? A case study in ladybird beetles.
Vertically transmitted bacterial symbionts are common in arthropods. However, estimates of their incidence and diversity are based on studies that test for a single bacterial genus and often only include small samples of each host species. Focussing on ladybird beetles, we collected large samples from 21 species and tested them for four different bacterial symbionts. Over half the species were infected, and there were often multiple symbionts in the same population. In most cases, more females than males were infected, suggesting that the symbionts may be sex ratio distorters. Many of these infections would have been missed in previous studies as they only infect a small proportion of the population. Furthermore, 11 out of the 17 symbionts discovered by us were either in the genus Rickettsia or Spiroplasma, which are rarely sampled. Our results suggest that the true incidence and diversity of bacterial symbionts in insects may be far greater than previously thought.


Influence of the endosymbiont of Blastocrithidia culicis and Crithidia deanei on the glycoconjugate expression and on Aedes aegypti interaction.
Blastocrithidia culicis and Crithidia deanei are trypanosomatid protozoa of insects that normally contain intracellular symbiotic bacteria. The protozoa can be rid of their endosymbionts by antibiotics, producing a cured cell line. Here, we analyzed the glycoconjugate profiles of endosymbiont-harboring and cured strains of B. culicis and C. deanei by Western blotting and flow cytometry analyses using lectins that recognize specifically sialic acid and mannose-like residues. The absence of the endosymbiont increased the intensity of the lectins binding on both trypanosomatids. In addition, wild and cured strain-specific glycoconjugate bands were identified. The role of the surface saccharide residues on the interaction with explanted guts from Aedes aegypti gut was assessed. The aposymbiotic strains of B. culicis and C. deanei presented interaction rates 3.3- and 2.3-fold lower with the insect gut, respectively, when compared with the endosymbiont-bearing strains. The interaction rate of sialidase-treated cells of the wild and cured strains of B. culicis and C. deanei was reduced in at least 90% in relation to the control. The interaction of B. culicis (wild strain) with explanted guts was inhibited in the presence of mucin (56%), fetuin (62%), sialyllactose (64%) and alpha-methyl-D-mannoside (80%), while in C. deanei (wild strain) the inhibition was 53%, 56%, 79% and 34%, respectively. Collectively, our results suggest a possible involvement of sialomolecules and mannose-rich glycoconjugates in the interaction between insect trypanosomatids and the invertebrate host.


Mechanical properties, biological behaviour and drug release capability of nano TiO2-HAp-Alginate composite scaffolds for potential application as bone implant material.
Nanocomposite scaffolds of TiO2 and hydroxyapatite nanoparticles with alginate as the binding agent were fabricated using the freeze drying technique. TiO2, hydroxyapatite and alginate were used in the ratio of 1:1:4. The scaffolds were characterized using X-ray diffraction, fourier transform infrared spectroscopy, and scanning electron microscopy. The biocompatibility of the scaffolds was evaluated using cell adhesion and MTT assay on osteosarcoma (MG-63) cells. Scanning electron microscopy analysis revealed that cells adhered to the surface of the scaffolds with good spreading. The mechanical properties of the scaffolds were investigated using dynamic mechanical analysis. The swelling ability, porosity, in vitro degradation, and biomineralization of the scaffolds were also evaluated. The results indicated controlled swelling, limited degradation, and enhanced biomineralization. Further, drug delivery studies of the scaffolds using the chemotherapeutic drug methotrexate exhibited an ideal drug release profile. These scaffolds are proposed as potential candidates for bone tissue engineering and drug delivery applications.


Highly purified mycobacterial phosphatidylinositol mannosides drive cell-mediated responses and activate NKT cells in cattle.
Mycobacterial lipids play an important role in the modulation of the immune response upon contact with the host. Using novel methods, we have isolated highly purified phosphatidylinositol mannoside (PIM) molecules (phosphatidylinositol dimannoside [PIM2], acylphosphatidylinositol dimannoside [AcPIM2], diacyl-phosphatidylinositol dimannoside [Ac2PIM2], acylphosphatidylinositol hexamannoside [AcPIM6], and diacylphosphatidylinositol hexamannoside [Ac2PIM6]) from virulent Mycobacterium tuberculosis to assess their potential to stimulate peripheral blood mononuclear cell (PBMC) responses in Mycobacterium bovis-infected cattle. Of these molecules, one (AcPIM6) induced significant levels of gamma interferon (IFN-γ) in bovine PBMCs. Three PIM molecules (AcPIM6, Ac2PIM2, and Ac2PIM6) were shown to drive significant proliferation in bovine PBMCs. AcPIM6 was subsequently used to phenotype the proliferating cells by flow cytometry. This analysis demonstrated that AcPIM6 was predominantly recognized by CD3(+) CD335(+) NKT cells. In conclusion, we have identified PIM lipid molecules that interact with bovine lymphocyte populations, and these lipids may be useful as future subunit vaccines or diagnostic reagents. Further, these data demonstrate, for the first time, lipid-specific NKT activation in cattle.


Genetic and biochemical characterization of hyicin 3682, the first bacteriocin reported for Staphylococcus hyicus.
Hyicin 3682, the first bacteriocin reported for Staphylococcus hyicus, is a BsaCOL variant produced by S. hyicus 3682, a strain isolated from bovine milk. Hyicin 3682 is found in the culture supernatant, is bactericidal and its producing strain exhibits a much broader spectrum of antimicrobial activity than the producing strain of BsaCOL against several Gram-positive bacteria, which include foodborne pathogens, food-spoilage microorganisms and bacterial species of medical and veterinary importance. Sequencing of the genome of S. hyicus 3682 provided the nucleotide sequence of the entire gene cluster involved in hyicin 3682 production, which seems to be located on pRJ109, the single plasmid carried by this strain. This gene cluster is expressed and consists of 8525bp and of eight genes (hyiA, hyiB, hyiC, hyiD, hyiP, hyiF, hyiE and hyiG) encoded on the same DNA strand. The mature lantibiotic exhibits 91% identity to BsaCOL and its molecular mass was found to be ∼26Da higher due to two amino acid substitutions. S. hyicus 3682 proved to be only partially immune to its cognate bacteriocin up to 1024 AU/ml. Therefore, hyicin 3682, the first Bsa variant reported in coagulase-negative staphylococci, does exhibit antimicrobial and siblicidal activities.


Brief reactive psychosis in a deaf man.
A prelingually deaf man developed a brief reactive psychosis that was influenced by sociocultural, community, and interpersonal conflicts. Resolution of symptoms followed interventions that addressed all areas of conflict.


Tentorial Notch Meningiomas: Innovative Preoperative Management and Literature Review.
Tentorial meningiomas account for only 3-6% of all intracranial meningiomas. Among them, tentorial incisura (notch) location must be considered as a subgroup with specific surgical anatomy and indications, morbidity, and mortality. In this study, we propose an update on preoperative management in order to reduce postoperative deficits. We retrospectively collected adult patients treated for incisural meningioma between January 1992 and December 2016 in two different neurosurgical departments. Demographic, clinical, and neuroradiological preoperative and postoperative data were analyzed. In the most recent subgroup of tumors, a preoperative digital simulation was performed to define a volumetric digital quantification of the tumor resection. A review of the pertinent literature has been also done. We included 26 patients. The median age was 58.4 years. Onset neurological signs were cranial nerve deficit in 9 patients, hemiparesis in 7, gait disturbance in 3, and intracranial hypertension in 3 patients. Simpson grade I removal was achieved in 12 patients, II in 10, III in 3, and IV in 1 patient. An overall rate of 23% postoperative complications was observed. The average follow-up duration was 68.5 months. Residual tumor was reported in 8 patients. Five patients underwent gamma knife radiosurgery. In 34.6% of patients, the surgical approach was chosen with preoperative digital planning estimating the potential volume of postoperative residual tumor, the target for radiosurgical treatment. A multidisciplinary approach to plan incisural meningiomas management is important. To lower postoperative morbidity and mortality, a careful preoperative case analysis is useful. A planned residual tumor, supported by preoperative simulation imaging, could be safely treated with radiosurgery.


[A comparative analysis of organization of care for patients with stroke in Russia, Europe and the United States].
Studies of the systems of medical care for patients with acute disorders of brain circulation indicate that well-organized "stroke" service promotes morbidity decrease, lowers neurological deficit expression and restriction of social and daily activities. At the same time, there are essential differences in the scope of the medical care, which a patient can receive in different countries and no consensus on the most optimal system of medical scope for patients with stroke at different stages. The recent statistical reviews confirm that a patient admitted to specialized stroke departments has a less chance to die or to be a handicap. The article analyzes current systems service for patients with acute disorders of brain blood circulation in the United States, Europe and Russia.


Delay discounting in currently using and currently abstinent cocaine-dependent outpatients and non-drug-using matched controls.
Higher rates of delay discounting have been consistently noted in substance abusers compared to non-drug-using matched controls. Additional data from some studies comparing discounting rates in current versus former substance abusers suggest that discounting rates may be adaptable and that drug abstinence may be associated with reductions in discounting. The primary purpose of the present study was to determine whether a period of cocaine abstinence (at least 30 days) resulted in altered discounting rates of money in a population of primary cocaine-dependent patients compared to current cocaine users and non-drug-using matched controls. Results suggest that there was no difference in discounting between currently abstinent and currently using cocaine-dependent outpatients. When these two groups were combined, cocaine-dependent patients showed higher discounting rates than non-drug-using matched controls. These data replicate previous work in cocaine-dependent and other substance abusers compared to non-drug-using controls and suggest that a longer period of abstinence may be required to modify discounting in this population.


Comparison of transradial and transfemoral access for transcatheter arterial embolization of iatrogenic renal hemorrhage.
There are few reports of renal artery embolization (RAE) via transradial access (TRA) for renal hemorrhage, and none have compared outcomes of RAE via TRA and transfemoral access (TFA). The objective was to compare technical and clinical outcomes in patients undergoing RAE via TRA or TFA for iatrogenic renal hemorrhage. This study included 45 RAE procedures (16 TRA and 29 TFA) for iatrogenic renal hemorrhage in 43 patients performed at a tertiary referral center between October 2018 and December 2020. Information regarding underlying diseases, coagulation status, angiographic and embolization procedure details, technical and clinical successes, and complications were retrospectively evaluated. There were no differences in demographics, underlying diseases, updated Charlson comorbidity scores, angiographic findings, and volume of contrast material between the TRA and TFA groups. By contrast, prothrombin time and international normalized ratio were significantly lower in the TRA than in the TFA group. Embolic materials differed significantly in the two groups. Procedure duration, fluoroscopy time, digital subtraction angiography number, and dose area product were slightly lower in the TRA than in the TFA group, but the differences were not statistically significant. Technical and clinical success rates in the TRA and TFA groups were 100% and 96.6%, and 100% and 96.6%, respectively. No patient in either group experienced procedure-related complications during a 4 week follow-up period. RAE via TRA in the management of iatrogenic renal hemorrhage was safe and feasible, with similar procedure duration and radiation exposure to RAE via TFA. TRA may be an acceptable alternative to TFA in these patients.


Safety of regular use of long-acting beta agonists as monotherapy or added to inhaled corticosteroids in asthma. A systematic review.
Safety of long-acting beta agonists (LABA) has been questioned and recent evidence suggested a detrimental effect on asthma control as well as an increased risk of death. To evaluate the safety of regular use of LABA compared with placebo or LABA added to inhaled corticosteroids (ICS) compared with ICS in persistent asthma. Randomized studies from MEDLINE, EMBASE, and Cochrane Controlled Trials Register were identified. Additionally, AstraZeneca, GlaxoSmithKline, Novartis and FDA clinical trials databases were searched. Primary outcomes were asthma exacerbations (AE) requiring systemic corticosteroids or hospitalization, life-threatening exacerbations and asthma-related deaths. We identified 92 randomized clinical trials with 74,092 subjects. LABA (as monotherapy) reduced exacerbations requiring corticosteroids (Relative Risk [RR]=0.80; 95% CI, 0.73-0.88), without detrimental effects on hospitalizations or life-threatening episodes. Contrarily, LABA showed a significant increase in asthma-related deaths (Relative Risk=3.83; 95% CI, 1.21-12.14). Subgroup analysis suggests that children, patients receiving salmeterol, and a duration of treatment>12 weeks are associated with a higher risk of serious adverse effects; also there was a protective effect of concomitant use of ICS. On the other hand, combination of LABA/ICS reduced exacerbations (RR=0.73; 95% CI, 0.67-0.79), and hospitalizations (RR=0.58, 95% CI, 0.45-0.74). Combined therapy was also equivalent to ICS in terms of life-threatening episodes and asthma-related deaths. Again, children and use of salmeterol were associated with an increased risk of some severe outcomes as compared with adults and formoterol users, respectively. This review reinforced the international recommendations in terms of the use of LABA remains the preferred add-on therapy to ICS for patients whose disease cannot adequately controlled with ICS, and that LABA cannot be prescribed as a monotherapy. Nevertheless, in spite of the protective effect of the ICS, children and salmeterol use still show an increased risk of non-fatal serious adverse events.


Designing and Interpreting Limiting Dilution Assays: General Principles and Applications to the Latent Reservoir for Human Immunodeficiency Virus-1.
Limiting dilution assays are widely used in infectious disease research. These assays are crucial for current human immunodeficiency virus (HIV)-1 cure research in particular. In this study, we offer new tools to help investigators design and analyze dilution assays based on their specific research needs. Limiting dilution assays are commonly used to measure the extent of infection, and in the context of HIV they represent an essential tool for studying latency and potential curative strategies. Yet standard assay designs may not discern whether an intervention reduces an already miniscule latent infection. This review addresses challenges arising in this setting and in the general use of dilution assays. We illustrate the major statistical method for estimating frequency of infectious units from assay results, and we offer an online tool for computing this estimate. We recommend a procedure for customizing assay design to achieve desired sensitivity and precision goals, subject to experimental constraints. We consider experiments in which no viral outgrowth is observed and explain how using alternatives to viral outgrowth may make measurement of HIV latency more efficient. Finally, we discuss how biological complications, such as probabilistic growth of small infections, alter interpretations of experimental results.


Increasing of Blood-Brain Tumor Barrier Permeability through Transcellular and Paracellular Pathways by Microbubble-Enhanced Diagnostic Ultrasound in a C6 Glioma Model.
Most of the anticancer agents cannot be efficiently delivered into the brain tumor because of the existence of blood-brain tumor barrier (BTB). The objective of this study was to explore the effect of microbubble-enhanced diagnostic ultrasound (MEUS) on the BTB permeability and the possible mechanism. Glioma-bearing rats were randomized into three groups as follows: the microbubble-enhanced continued diagnostic ultrasound (MECUS) group; the microbubble-enhanced intermittent diagnostic ultrasound (MEIUS) group and the control group. The gliomas were insonicated through the skull with a diagnostic ultrasound and injected with microbubbles through the tail veins. Evans Blue (EB) and dynamic contrast-enhanced-MRI were used to test changes in the BTB permeability. Confocal laser scanning microscopy was used to observe the deposition of the EB in the tumor tissues. The distribution and expression of junctional adhesion molecule-A (JAM-A) and calcium-activated potassium channels (KCa channels) were detected by a Western blot, qRT-PCR, and immunohistochemical staining. In the MEUS groups, the EB extravasation (11.0 ± 2.2 μg/g in MECUS group and 17.9 ± 2.3 μg/g in MEIUS group) exhibited a significant increase compared with the control group (5.3 ± 0.9 μg/g). The MEIUS group had more EB extravasation than the MECUS group. The Ktrans value of the dynamic contrast-enhanced-MRI in the MEUS groups was higher than that of the control group and correlated strongly with the EB extravasation in the tumor (R2 = 0.97). This showed that the Ktrans value might be a non-invasive method to evaluate the BTB permeability in rat glioma after microbubble-enhanced ultrasound treatment.Western blot, qRT-PCR and immunohistochemical staining revealed that MEUS increased the KCa channels expression and reduced JAM-A expression in glioma. This change was more obvious in the MEIUS group than in the MECUS group. The results demonstrated that MEUS effectively increased the BTB permeability in glioma. The mechanisms might involve the up-regulation of KCa channels expression and affecting the formation of tight junctions in the BTB by a reduction of JAM-A expression. These findings might provide some new guidance for glioma drug therapy.


Poisoning the spindle: serendipity and discovery of the anti-tumor properties of the Vinca alkaloids.
In 1995, Canadian scientists Robert Noble and Charles Beer were inducted into the Canadian Medical Hall of Fame for their 1950s "discovery" of Vinblastine. Their "chance" finding of an anticancer drug in the leaves of the periwinkle plant (Vinca rosea, Linn.), is used to explore the historical issue of discovery, accidental discovery, and priority. The elements of the discovery are reconstructed through the oral testimony of key players and their published and unpublished records. Several "unsung heroes" played key roles in this project and reasons for their relative invisibility will be presented. Special attention is paid to the relationship between the small Canadian academic group working at UWO and the large pharmaceutical company (Eli Lilly) engaged in similar research at the same time.


Parents' experience of coming to know the care of a chronically ill child.
The family is the primary source of care for a chronically ill child, and it is the parents who must manage the child's illness on a daily basis. This qualitative study was undertaken to investigate the ways in which 10 two-parent families of children with juvenile arthritis experience their child's illness. In this paper the theme of coming to terms with the management of the illness and what it entails for the parents is examined. The data provide evidence of how the parents learn, and their efforts and experience of learning to care for the child on a daily basis. This is a complex process and includes the different phases the parents experience as they move through the learning process. The findings suggest that the parents learn the child's care and make adjustments to the demands of managing the child's illness in a way that works best for them.


Structure-function analysis of human stomatin: A mutation study.
Stomatin is an ancient, widely expressed, oligomeric, monotopic membrane protein that is associated with cholesterol-rich membranes/lipid rafts. It is part of the SPFH superfamily including stomatin-like proteins, prohibitins, flotillin/reggie proteins, bacterial HflK/C proteins and erlins. Biochemical features such as palmitoylation, oligomerization, and hydrophobic "hairpin" structure show similarity to caveolins and other integral scaffolding proteins. Recent structure analyses of the conserved PHB/SPFH domain revealed amino acid residues and subdomains that appear essential for the structure and function of stomatin. To test the significance of these residues and domains, we exchanged or deleted them, expressed respective GFP-tagged mutants, and studied their subcellular localization, molecular dynamics and biochemical properties. We show that stomatin is a cholesterol binding protein and that at least two domains are important for the association with cholesterol-rich membranes. The conserved, prominent coiled-coil domain is necessary for oligomerization, while association with cholesterol-rich membranes is also involved in oligomer formation. FRAP analyses indicate that the C-terminus is the dominant entity for lateral mobility and binding site for the cortical actin cytoskeleton.


VEGF plasma pattern in ovulation induction: evidence for an episodic secretion and lack of immediate effect of hCG.
Vascular endothelial growth factor (VEGF) is a potent stimulator of vascular proliferation and permeability. Ovarian granulosa cells have been identified as a major source of the cytokine and r-hCG was able to stimulate VEGF mRNA expression in vitro. In this study we have investigated the immediate effect of ovulation induction with hCG on peripheral VEGF levels in 6 women with primary infertility enrolled in the IVF/ET program. The patients underwent a 24-hour continuous blood withdrawal with sampling intervals of 15 minutes starting from 5 hours before ovulation induction with 10.000 IU hCG. Ovulation induction with hCG had no significant immediate effect on mean peripheral VEGF levels. However, VEGF plasma levels did exhibit significant episodic fluctuations with rapid increases every 90-120 minutes without any relation to circulating hCG levels. Taken together, the results of this study suggest that VEGF is released episodically and that systemic VEGF levels are not acutely altered by ovulation induction with hCG.


ACE inhibition with cilazapril improves myocardial perfusion to the ischemic regions during exercise: a pilot study.
This study was performed to examine whether cilazapril, a novel nonsulfhydril angiotensin-converting enzyme (ACE) inhibitor, may improve regional myocardial perfusion at exercise in patients with coronary heart disease (CHD). In a single-blind, nonrandomized trial, 5 mg cilazapril or placebo was administered to eight patients with documented CHD and stable exertional angina. Multistage bicycle exercise tests were performed and each patient served as his own control. At peak exercise, as well as at rest, [99mTc]hexakis-2-methoxy-2-isobutylisonitrile myocardial images were obtained. Percent myocardial activity differences (%AD) between exercise and resting images were compared (cilazapril versus placebo). Heart rate and blood pressure were not significantly different between trials. However, after cilazapril administration, %AD was higher than after placebo, with relative differences between trials of greater than 30%, along with alleviation of clinical symptoms in seven of eight patients. These data suggest that in patients with stable-effort angina, ACE inhibition with cilazapril is able to redistribute myocardial blood flow and to improve regional oxygen supply to the ischemic myocardium.


The LoFric catheter: new technology improves an old technique.
The LoFric catheter is a hydrophilic, nonlatex plastic catheter for use in adults and children. Immersing the catheter in water produces a slippery, protective coating on the catheter. This protective coating prevents trauma to the mucosal surface. Because of its slippery surface even patients who have difficulty using a conventional catheter are usually able to use a LoFric catheter.


Chromosome structure in Chilocorus (Coleoptera: Coccinellidae). II. The asynchronous replication of constitutive heterochromatin.
Chromosome replication has been analysed in four species of Chilocorus. In C. ORBUS Csy., C. tricyclus Smith, and C. hexacyclus Smith, centric regions of all chromosomes are last to replicate, preceded in order by heterochromatic arms and euchromatic arms. In C. stigma Say, very late replication of centric regions can be detected only in otherwise wholly euchromatic chromosomes (= monophasics); in chromosomes with one arm heterochromatic ( = disphasics), these arms are last to replicate. Based on pachytene bivalent morphology and chromosome banding patterns, and supported by autoradiographic data, models are presented for the general organisation of Chilocorus chromosomes. All chromosomes in the first three species are subdivided into euchromatic arm, centric heterochromatin, and either a second euchromatic are (monophasics) or a heterochromatic arm (diphasics). Chilocorus stigma diphasics apparently lack distinct centric organisation, and are therefore divided into euchromatic and heterochromatic arms only.


Pharmacokinetics and tolerability of daptomycin at doses up to 12 milligrams per kilogram of body weight once daily in healthy volunteers.
Daptomycin, a novel lipopeptide, is bactericidal against a broad range of gram-positive strains, including methicillin- (MRSA) and vancomycin-resistant Staphylococcus aureus. Daptomycin is approved at 4 mg/kg of body weight given intravenously once daily for the treatment of complicated skin and skin structure infections and at 6 mg/kg for the treatment of S. aureus bloodstream infections (bacteremia), including right-sided endocarditis caused by methicillin-susceptible S. aureus and MRSA. The present study was designed to evaluate the multiple-dose pharmacokinetics and safety of daptomycin at doses of 6 to 12 mg/kg in healthy volunteers. Three cohorts of 12 subjects each were given daptomycin (10 mg/kg) or placebo once daily for 14 days, daptomycin (12 mg/kg) or placebo once daily for 14 days, or daptomycin (6 or 8 mg/kg) once daily for 4 days. Daptomycin produced dose-proportional increases in the area under the plasma concentration-time curve and in trough daptomycin levels and nearly dose-proportional increases in peak daptomycin concentrations. Other pharmacokinetic parameters measured on day 1 and at steady state were independent of the dose, including the half-life (approximately 8 h), weight-normalized plasma clearance (9 to 10 ml/h/kg), and volume of distribution (approximately 100 ml/kg). Plasma protein binding was 90% to 93% and was independent of the daptomycin concentration. Daptomycin did not produce electrocardiographic abnormalities or electrophysiological evidence of muscle or nerve toxicity. Daptomycin was well tolerated in subjects dosed with up to 12 mg/kg intravenously for 14 days. Doses of daptomycin higher than 6 mg/kg once daily may be considered in further studies to evaluate the safety and efficacy of daptomycin in difficult-to-treat infections.


[Potential consequences of the sudden postnatal drop of estrogen levels in preterm neonates].
Estrogens have profound effects on bone- and lipid homeostasis, modulate immune functions and play a major role in the regulation of the development and function of central nervous system, cardiovascular system and respiratory system. They induce hepatic protein production. There is a strong connection between estrogens and several hormone systems including growth hormone--IGF axis and renin-angiotensin system. The extragenital effects of estrogens are probably more evident in the fetus than in fertile women. However, direct data are not available because of the lack of estrogen-deficient pregnancy models. Theoretically, in immature infants the premature cessation of in utero high estrogen levels is associated with the progression of perinatal acute complications. The volume of uterus in female premature infants is lower than in term newborns, the plasma levels of atherogen lipids are high, osteopenia due to inadequate bone acquisition is frequent. Inflammatory complications are common. Recently, the physiological effects of estrogen- and progesterone supplementation of premature infants have been evaluated in a pilot study. The preliminary results indicate, that the risk of bronchopulmonary dysplasia, osteopenia might be decreased in treated infants. Further studies are needed to confirm the effectivity and long term safety of estrogen supplementation of preterm neonates.


Factors That Can Promote the Green Entrepreneurial Intention of College Students: A Fuzzy Set Qualitative Comparative Analysis.
Green entrepreneurship has a huge role in solving environmental degradation and social problems. As today's youth are tomorrow's entrepreneurs, enhancing their green entrepreneurial intention will contribute to the sustainable development of economy in the future. The existing literature has examined the green entrepreneurial intention of college students based on self-efficacy, entrepreneurial creativity, entrepreneurship education, financial support, sustainable development values, and other influencing factors. However, these studies focus on net effect of factors on the results of college students' green entrepreneurial intention, ignoring the combination of multiple factors, and the relationship between different configurations of factors and the results of college students' green entrepreneurial intention. Therefore, this study aimed to understand and analyze the influence of the complex relationship between multiple antecedents (entrepreneurial creativity, future self-continuity, green cognition, entrepreneurship culture, entrepreneurship education, and financial support) on college students' green entrepreneurial intention from a comprehensive perspective. Based on 207 questionnaires collected from colleges in the coastal cities of China, this study used the fuzzy set qualitative comparative analysis method for data analysis. The results showed three dominant paths of great significance to college students' high green entrepreneurial intention: entrepreneurial creativity-green cognition-dominant path; entrepreneurial creativity-financial support-dominant path; and the future self-continuity-entrepreneurship culture-entrepreneurship education-dominant path. The results of this study can help college educators to plan courses on innovative thinking and green entrepreneurship to improve college students' entrepreneurial creativity and green cognitive ability.


Olympic and world sport: making transnational society?
This paper introduces the special issue of the British Journal of Sociology on the subject of the transnational aspects of Olympic and world sport. The special issue is underpinned by the perspective that because sport provides a space for the forging of transnational connections and global consciousness, it is increasingly significant within contemporary processes of globalization and the making of transnational society. In this article, we examine in turn eight social scientific themes or problems that are prominent within the special issue: globalization, glocalization, neo-liberal ideologies and policies, transnational society, securitization, global civil society, transnational/global public sphere, and fantasy/imagination. We conclude by highlighting five 'circles' of future research inquiry within world sport that should be explored by social scientists.


In Vitro Study of the Metabolic Characteristics of Eight Isoquinoline Alkaloids from Natural Plants in Rat Gut Microbiota.
Gut microbiota is populated with an immense number of microorganisms, which can be regulated by dietary components and drugs to markedly affect the nutritional and health status of the host. Eight medicinal isoquinoline alkaloids from natural plants were cultured anaerobically with rat gut microbiota and an LC/MSn-IT-TOF technique was used to identify the resulting metabolites. Palmatine, tetrahydropalmatine, dauricine, and tetrandrine containing nitro-hexatomic isoquinoline rings could be easily transformed by the intestinal flora in vitro and a total of nine demethylated metabolites were detected. However, sinomenine, homoharringtonine, harringtonine, and galanthamine, which all contained benzazepine, could not undergo demethylation. Computer-assisted docking was used to analyze the binding between these compounds and sterol 14α-demethylase. The computational results demonstrated that hydrophobic interactions were the main driving force for binding, but the steric hindrance produced by the benzazepine structure resulted in a weak interaction between the hit compounds and the enzyme. This work illustrated that gut microbiota were important in the metabolism of isoquinoline alkaloids.


A preliminary study of the appropriation of Van Helmont's oeuvre in Britain in chymistry, medicine and natural philosophy.
Van Helmont's work was of major importance in seventeenth-century medicine, chymistry and natural philosophy. His work was a source of inspiration and mystery and an authoritas. His oeuvre was, together with that of many others, the culminating point of an ongoing process, starting in the Middle Ages, of turning medicine into a scientific discipline. In this essay, the appropriation, that is, the process of assimilation of an author's work by other scholars, of Van Helmont's oeuvre in England will be studied among chymists, physicians and natural philosophers (the distinctions between these three groups is primarily conceptual, but in practice hard to distinguish). Appropriation reminds us that the process of assimilating ideas of an author by contemporaries or later generations is not a passive activity, for scholars actively adapt and interpret them in new ways not initially envisaged by its original author.


Effects of a triclosan dentifrice on plaque formation, gingivitis and gingival bleeding in pregnant women: five-month clinical results.
The objective of this study was to determine the effects of a triclosan/copolymer dentifrice on plaque formation, gingivitis and gingival bleeding in pregnant subjects. This double-blind clinical study was carried out in 180 women at 3 months of pregnancy. The subjects were stratified into two balanced groups according to their baseline plaque, gingivitis and bleeding scores. Subjects received a thorough dental prophylaxis and were assigned to brush with either a placebo or triclosan dentifrice for five months. They were instructed to brush their teeth as they normally would, twice a day for one minute per brushing. Follow-up examinations after five months of dentifrice use evaluated supragingival plaque, gingivitis and gingival bleeding. After five months, the triclosan dentifrice significantly reduced plaque formation, gingivitis and gingival bleeding by 40.5%, 22.5% and 35.3%, respectively, compared to the placebo group (p<0.05).


Phenome-Wide Association Study of Polygenic Risk Score for Alzheimer's Disease in Electronic Health Records.
Alzheimer's disease (AD) is the most common form of dementia and a growing public health burden in the United States. Significant progress has been made in identifying genetic risk for AD, but limited studies have investigated how AD genetic risk may be associated with other disease conditions in an unbiased fashion. In this study, we conducted a phenome-wide association study (PheWAS) by genetic ancestry groups within a large academic health system using the polygenic risk score (PRS) for AD. PRS was calculated using LDpred2 with genome-wide association study (GWAS) summary statistics. Phenotypes were extracted from electronic health record (EHR) diagnosis codes and mapped to more clinically meaningful phecodes. Logistic regression with Firth's bias correction was used for PRS phenotype analyses. Mendelian randomization was used to examine causality in significant PheWAS associations. Our results showed a strong association between AD PRS and AD phenotype in European ancestry (OR = 1.26, 95% CI: 1.13, 1.40). Among a total of 1,515 PheWAS tests within the European sample, we observed strong associations of AD PRS with AD and related phenotypes, which include mild cognitive impairment (MCI), memory loss, and dementias. We observed a phenome-wide significant association between AD PRS and gouty arthropathy (OR = 0.90, adjusted p = 0.05). Further causal inference tests with Mendelian randomization showed that gout was not causally associated with AD. We concluded that genetic predisposition of AD was negatively associated with gout, but gout was not a causal risk factor for AD. Our study evaluated AD PRS in a real-world EHR setting and provided evidence that AD PRS may help to identify individuals who are genetically at risk of AD and other related phenotypes. We identified non-neurodegenerative diseases associated with AD PRS, which is essential to understand the genetic architecture of AD and potential side effects of drugs targeting genetic risk factors of AD. Together, these findings expand our understanding of AD genetic and clinical risk factors, which provide a framework for continued research in aging with the growing number of real-world EHR linked with genetic data.


Selection and evaluation of three interventional procedures for achalasia based on long-term follow-up.
To determine the best method out of the three types of interventional procedure for achalasia based on a long-term follow-up. The study cohort was comprised of 133 patients of achalasia. Among them, 60 patients were treated under fluoroscopy with pneumatic dilation (group A), 8 patients with permanent uncovered or antireflux covered metal stent dilation (group B), and 65 patients with temporary partially covered metal stent dilation (group C). One hundred and thirty dilations were performed on the 60 patients of group A (mean 2.2 times per case). The mean diameter of the strictured cardia was 3.3+/-2.1 mm before dilation and 10.6+/-3.8 mm after dilation. The mean dysphagia score was 2.7+/-1.4 before dilation and 0.9+/-0.3 after dilation. Complications in group A were chest pain (n=30), reflux (n=16), and bleeding (n=6). Thirty-six patients (60%) in group A exhibited dysphagia relapse during a 12-month follow-up, and 45 patients (90%) out of 50 exhibited dysphagia relapse during a 36-month follow-up. Five uncovered and 3 antireflux covered expandable metal stents were permanently placed in the 8 patients of group B. The mean diameter of the strictured cardia was 3.4+/-1.9 mm before dilation and 19.5+/-1.1 mm after dilation. The mean dysphagia score was 2.6+/-1.3 before dilation and 0.4+/-0.1 after dilation. Complications in group B were chest pain (n=6), reflux (n=5), bleeding (n=3), and hyperplasia of granulation tissue (n=3). Four patients (50%) in group B exhibited dysphagia relapse during a 12-month follow-up, and 2 case (66.7%) out of 3 patients exhibited dysphagia relapse during a 36-month follow-up. Sixty-five partially covered expandable metal stents were temporarily placed in the 65 patients of group C and withdrawn after 3-7 days via gastroscopy. The mean diameter of the strictured cardia was 3.3+/-2.3 mm before dilation and 18.9+/-3.5 mm after dilation. The mean dysphagia score was 2.4+/-1.3 before dilation and 0.5+/-0.2 after dilation. Complications in group C were chest pain (n=26), reflux (n=13), and bleeding (n=8). 6 patients (9.2%) out of 65 exhibited dysphagia relapse during a 12-month follow-up, and 8 patients (14.5%) out of 55 exhibited dysphagia relapse during a 36-month follow-up. All the stents were inserted and withdrawn successfully. The follow-up in groups A-C lasted 12-96 months. Temporary partially covered metal stent dilation is one of the best methods with interventional procedure for achalasia in terms of long-term follow-up.


African soil properties and nutrients mapped at 30 m spatial resolution using two-scale ensemble machine learning.
Soil property and class maps for the continent of Africa were so far only available at very generalised scales, with many countries not mapped at all. Thanks to an increasing quantity and availability of soil samples collected at field point locations by various government and/or NGO funded projects, it is now possible to produce detailed pan-African maps of soil nutrients, including micro-nutrients at fine spatial resolutions. In this paper we describe production of a 30 m resolution Soil Information System of the African continent using, to date, the most comprehensive compilation of soil samples ([Formula: see text]) and Earth Observation data. We produced predictions for soil pH, organic carbon (C) and total nitrogen (N), total carbon, effective Cation Exchange Capacity (eCEC), extractable-phosphorus (P), potassium (K), calcium (Ca), magnesium (Mg), sulfur (S), sodium (Na), iron (Fe), zinc (Zn)-silt, clay and sand, stone content, bulk density and depth to bedrock, at three depths (0, 20 and 50 cm) and using 2-scale 3D Ensemble Machine Learning framework implemented in the mlr (Machine Learning in R) package. As covariate layers we used 250 m resolution (MODIS, PROBA-V and SM2RAIN products), and 30 m resolution (Sentinel-2, Landsat and DTM derivatives) images. Our fivefold spatial Cross-Validation results showed varying accuracy levels ranging from the best performing soil pH (CCC = 0.900) to more poorly predictable extractable phosphorus (CCC = 0.654) and sulphur (CCC = 0.708) and depth to bedrock. Sentinel-2 bands SWIR (B11, B12), NIR (B09, B8A), Landsat SWIR bands, and vertical depth derived from 30 m resolution DTM, were the overall most important 30 m resolution covariates. Climatic data images-SM2RAIN, bioclimatic variables and MODIS Land Surface Temperature-however, remained as the overall most important variables for predicting soil chemical variables at continental scale. This publicly available 30-m Soil Information System of Africa aims at supporting numerous applications, including soil and fertilizer policies and investments, agronomic advice to close yield gaps, environmental programs, or targeting of nutrition interventions.


Antimalarial Plants Used across Kenyan Communities.
Malaria is one of the serious health problems in Africa, Asia, and Latin America. Its treatment has been met with chronic failure due to pathogenic resistance to the currently available drugs. This review attempts to compile phytotherapeutical information on antimalarial plants in Kenya based on electronic data. A comprehensive web search was conducted in multidisciplinary databases, and a total of 286 plant species from 75 families, distributed among 192 genera, were retrieved. Globally, about 139 (48.6%) of the species have been investigated for antiplasmodial (18%) or antimalarial activities (97.1%) with promising results. However, there is no record on the antimalarial activity of about 51.4% of the species used although they could be potential sources of antimalarial remedies. Analysis of ethnomedicinal recipes indicated that mainly leaves (27.7%) and roots (19.4%) of shrubs (33.2%), trees (30.1%), and herbs (29.7%) are used for preparation of antimalarial decoctions (70.5%) and infusions (5.4%) in Kenya. The study highlighted a rich diversity of indigenous antimalarial plants with equally divergent herbal remedy preparation and use pattern. Further research is required to validate the therapeutic potential of antimalarial compounds from the unstudied claimed species. Although some species were investigated for their antimalarial efficacies, their toxicity and safety aspects need to be further investigated.


TLR3 Mutations in Adult Patients With Herpes Simplex Virus and Varicella-Zoster Virus Encephalitis.
Defects in genes of the Toll-like receptor 3 (TLR3) pathway are associated with susceptibility to herpes simplex virus type 1 encephalitis (HSE). We analyzed a cohort of 11 adult Italian patients in whom viral encephalitis developed. We detected 2 rare missense mutations in TLR3: 1 in a patient with HSE (p.Leu297Val) and 1 in a patient with varicella-zoster virus encephalitis (p.Leu199Phe). Both mutations are extremely rare in human populations and have pathogenicity scores highly suggestive of a functional effect. Data herein expand the phenotypic spectrum of TLR3 mutations to varicella-zoster virus encephalitis and support the role of TLR3 genetic defects as risk factors for HSE in adults.


Parent-adolescent communication about sexual intercourse: an analysis of maternal reluctance to communicate.
A unified theory of behavior was applied to parent-adolescent communication about sexual intercourse to understand why some mothers speak less often with their children about not having sexual intercourse. According to the theory, parental decisions or intentions to engage in such conversations are a function of expectancies, social norms, self-concept, emotions, and self-efficacy. Data were collected from a random sample of 668 mother-adolescent dyads recruited from middle schools located in the Bronx community of New York City. Data were collected via self-administered surveys. Mother and adolescent reports on the frequency of parent-adolescent communication about sexual intercourse were obtained. Adolescents and mothers reported how often the mother had discussed 21 topics related to sexual behavior. Results supported the utility of the framework for understanding parent-adolescent communication about sexual intercourse. Significant maternal correlates included (a) expectancies about lacking knowledge, being embarrassed and encouraging children to think maturely and focus on school; (b) self-concept and perceiving that mothers who didn't talk with their children about sex were irresponsible; (c) emotions about feeling relaxed and comfortable; and (d) self-efficacy about the ease of talking with one's child. Implications for family based prevention programs are discussed.


Health care technology: nursing's challenge and opportunity.
The growth in health care technology is ubiquitous and has far reaching consequences both for users and providers. This paper explores how health care technology affects ours lives, presents the challenges inherent in its use, and also identifies some of the opportunities that it provides nurses.


Scalable ultrasmall three-dimensional nanowire transistor probes for intracellular recording.
New tools for intracellular electrophysiology that push the limits of spatiotemporal resolution while reducing invasiveness could provide a deeper understanding of electrogenic cells and their networks in tissues, and push progress towards human-machine interfaces. Although significant advances have been made in developing nanodevices for intracellular probes, current approaches exhibit a trade-off between device scalability and recording amplitude. We address this challenge by combining deterministic shape-controlled nanowire transfer with spatially defined semiconductor-to-metal transformation to realize scalable nanowire field-effect transistor probe arrays with controllable tip geometry and sensor size, which enable recording of up to 100 mV intracellular action potentials from primary neurons. Systematic studies on neurons and cardiomyocytes show that controlling device curvature and sensor size is critical for achieving high-amplitude intracellular recordings. In addition, this device design allows for multiplexed recording from single cells and cell networks and could enable future investigations of dynamics in the brain and other tissues.


Thalidomide has a significant effect in patients with thalassemia intermedia.
To investigate the effect of thalidomide in patients with thalassemia intermedia. We observed the effect of thalidomide in seven patients with thalassemia intermedia requiring blood transfusion. Four of the patients were transfusion-independent, and three patients were transfusion-dependent. For the four transfusion-independent patients, hemoglobin concentration increased significantly (≥2 g/dl) in three and moderately (1-2 g/dl) in one. After 3 months of treatment, hemoglobin concentration increased 3.2 ± 1.2 g/dl compared to pretreatment. Among the three transfusion-dependent patients, transfusion was terminated after one month of treatment in one patient and decreased >50% in the other two patients, accompanied by an increase in the average hemoglobin concentration. Thalidomide had a significant effect in patients with thalassemia intermedia. Further studies of a larger scale and more rigorous design are warranted.


GENOTYPE-ENVIRONMENT INTERACTION FOR CLIMATE AND COMPETITION IN A NATURAL POPULATION OF FLOUR BEETLES, TRIBOLIUM CASTANEUM.
The norm of reaction, the set of average phenotypes produced by a genotype in different environments, can be affected by spatial variation in natural selection especially when there exists genotype-environment interaction. In subdivided populations, the greater the genotype-environment interaction variance and the lower the migration rate, the more independent are the possible evolutionary trajectories for local adaptation. I examined genotype-environment interaction in the rate of population increase for lineages randomly derived from a wild population of Tribolium castaneum across a series of ecologically important environments. The lineages were derived from an outbred, wild-caught population by 14 generations of random genetic drift, during which the effective size of each lineage was approximately 22 breeding adults. The environments studied were the classic temperate-wet and cold-dry climates of Park (1954) in factorial combination with two genetic strains of a congeneric competitor, T. confusum. Much among-lineage genetic variation for rate of population increase was found for each of these ecologically important environments of climate and competition. Genotype-environment interaction accounted for 40.5% of the total among-lineage variance in rate of population increase signifying that the performance of a lineage in one environment is not necessarily a good predictor of its performance in another. Changing the genetic identity of the competitor changed the rate of increase of some lineages as much or more than changing the climatic conditions of temperature and humidity. This is the first empirical study to characterize the genotype-environment interaction variance associated with genetic variation in a competing congeneric species. This competitor-specific genetic variation in competitive ability may play an important role in coevolution in subdivided populations.


[DNA microarrays in parasitology and medical sciences].
The article presents the current knowledge on the microarray technique and its applications in medical sciences and parasitology. The first part of the article is focused on the technical aspects (microarray preparation, different microarray platforms, probes preparation, hybridization and signal detection). The article also describes possible ways of proceeding during laboratory work on organism of which the genome sequence is not known or has been only partially sequenced. The second part of the review describes how microarray technique have been, or possibly will be, used for better understanding parasite life cycles and development, host-parasite relationship, comparative genomics of virulent organisms, develpoment vaccines against the most virulent parasites and host responses to infection.


Magnetic resonance imaging in amyotrophic lateral sclerosis.
We aimed to investigate the importance of magnetic resonance imaging for the diagnostic process of the upper motor neuron involvement. Fifteen patients (Group 1) who were diagnosed with amyotrophic lateral sclerosis in the neurology department of the Sisli Etfal Hospital and 20 controls (Group 2) entered the study. Magnetic resonance imaging examinations were performed in the radiology clinic of the same hospital. T2 and proton density weighted axial images were obtained. These images were evaluated by two blind radiologists. The radiologists looked for two signs: the presence of a low signal intensity at the precentral cortex and the presence of symmetrical rounded foci of high signal intensity within the internal capsule on both T2 and proton density weighted images. For the first sign there was no statistically significant difference between the two groups but for the latter one there was a statistically significant difference. We think that the presence of the latter sign may make it possible for the radiologists to help the clinicians further in this difficult and confusing diagnosis.


Study of 1-3-2 type piezoelectric composite transducer array.
Based on a new structure of precise location and decoupling between the transducer elements, high frequency underwater transmission transducer arrays with 4 elements and 8 elements serried uniform linear array were studied, using novel 1-3-2 type piezoelectric composite as the sensing material. There are ceramic framework supports in the transverse and longitudinal directions in 1-3-2 type piezoelectric composite structure; the transducer is free from the influence of outside mechanical impact and the environment temperature change. Transducer and array samples have been designed, fabricated and measured. The resonant frequency is 150 kHz, resonant transmission response greater than 160 dB, and bandwidth is from 140 kHz to 160 kHz. The results indicate that, the transducer array has wide bandwidth, high sensitivity, stabile performance, and good coherence.


Reducing depression in pregnancy: designing multimodal interventions.
Research indicates that high levels of stress, low social support networks, and depression during pregnancy have a powerful negative effect on maternal functioning and infant developmental outcomes. Low-income, inner-city women from ethnic minority groups, whose levels of depression have been documented as higher than their white counterparts, are at increased risk, as are their infants. This article reviews the relevant research literature and proposes that "bundling" several social work treatments intended to reduce or prevent depression, expand social networks, and enhance mothers' knowledge of child development is more effective than any single approach. Joining treatments into one intervention approach offers multiple treatments for multiple problems and can be designed to be evaluated.


Composite acoustic medium with simultaneously negative density and modulus.
We fabricated an acoustic composite structure consisting of a periodic array of interspaced membranes and side holes. Experimental data on the transmission, effective density, and phase velocity are presented. The system exhibits two critical frequencies, omega{SH} and omega{c}. Our metamaterial is double negative and transparent for frequencies lower than omega{SH}. For the frequencies omega{SH}<omega<omega{c}, the medium is opaque and only the density is negative. For the frequencies above omega{c}, the system is double positive and transparent. The present medium exhibits a very wide double negative spectral range that opens the possibility of the application of metamaterials for "white lights."


Effect of substrate geometry on liquid-crystal-mediated nanocylinder-substrate interactions.
Using classical density functional theory, the liquid crystal (LC)-mediated interaction between a cylindrical nanoparticle and a structured substrate is studied. The surface is structured by cutting a rectangular groove into the surface. In the absence of the nanoparticle, a range of defect structures is formed in the vicinity of the groove. By varying the groove width and depth, the LC-mediated interaction changes from repulsive to attractive. This interaction is strongest when the groove is of comparable size to the nanoparticle. For narrow grooves the nanoparticle is attracted to the center of the groove, while for wider grooves there is a free energy minimum near the sidewalls.


Exploiting the Protein Corona from Cell Lysate on DNA Functionalized Gold Nanoparticles for Enhanced mRNA Translation.
This study describes the use of DNA functionalized gold nanoparticles (AuNPs) to enhance the synthesis of proteins in cell lysate and examines the mechanisms behind the enhanced mRNA translation. With an appropriate DNA oligomer sequence that hybridizes to the 3'-untranslated region of two mRNA of interest, insulin and green fluorescent protein (GFP), we found that these DNA conjugated AuNPs (AuNP-DNA) introduced into HeLa cell lysate enhanced the synthesis of insulin and GFP by up to 2.18 and 1.80-fold, respectively, over baseline production with just the mRNA present. The insulin synthesis was markedly reduced with non-DNA citrate-capped AuNP (1.25-fold) and AuNP-DNA with a nonspecific poly(T) sequence (1.25-fold). We showed that both nonspecific adsorption of ribosomes and translation factors to form a lysate protein corona on AuNP-DNA and weak hybridization between DNA oligomers and mRNA of interest were important factors that brought translation factors, ribosomes, and mRNA into close proximity of each other. This could reduce the recycling time of ribosomes during mRNA translation, thereby increasing the efficiency of protein synthesis. The outcome of this work shows that with rational DNA design, it could be possible to modulate intracellular biological processes with AuNP-DNA and increase their production of proteins for various biomedical applications.


Mitochondrial phosphatidylethanolamine level modulates Cyt c oxidase activity to maintain respiration capacity in Arabidopsis thaliana rosette leaves.
Phosphatidylethanolamine is the predominant phospholipid of the mitochondrial inner membrane. In Arabidopsis, pect1-4 mutants exhibit reduced cellular phosphatidylethanolamine levels owing to reduced CTP:phosphorylethanolamine cytidylyltransferase (PECT; EC 18.104.22.168) activity. Consequently, pect1-4 mutants may have decreased mitochondrial phosphatidylethanolamine levels, thereby affecting respiration capacity. Wild-type and pect1-4 plants grew similarly under a short-day condition until 5 weeks, when pect1-4 leaves had slightly less Chl. Total respiration was comparable between wild-type and pect1-4 leaves at 3 weeks and then increased 2-fold in the wild-type but only 1.1-fold in pect1-4 leaves. Compared with the wild type, the Cyt oxidase pathway capacity was reduced by 36% in pect1-4 leaves at 5 weeks and by 43% in pect1-4 mitochondria in 5-week-old rosette leaves. Maximal Cyt c oxidase (COX) activity was 20% lower in pect1-4 mitochondria than in wild-type mitochondria at 5 weeks despite comparable COX II protein levels in mitochondria at that time. Furthermore, COX II protein levels doubled in both wild-type and pect1-4 mitochondria between 3 and 5 weeks. Phosphatidylethanolamine levels were similar between mitochondria from these plants at 3 weeks and then increased by 6.4% in wild-type mitochondria and decreased by 6.5% in pect1-4 mitochondria by 5 weeks. Phosphatidylcholine levels compensated for the decreases in phosphatidylethanolamine levels. COX activity was lower in pect1-4 mitochondria at 5 weeks, most probably due to reduced phosphatidylethanolamine levels and/or an altered phosphatidylethanolamine:phosphatidylcholine ratio. Thus, PECT1 regulates mitochondrial phosphatidylethanolamine levels, which are important for maintaining respiration capacity in Arabidopsis leaves during prolonged growth under short-day conditions.


[Overweight and obesity; recommendations from the National Health Council].
The Health Council of the Netherlands has issued a report on overweight and obesity. These are considered major threats to personal health, the public health care services and economic welfare. Overweight and obesity are no longer considered variations of the norm, but as a disease. As genetically predisposing factors cannot be influenced, major initiatives to contain further deterioration of the problem must be on environmental factors i.e. on macronutrient intake and physical exercise. Special target groups (young people, people of low socioeconomic status and immigrants) need to be defined. Government, health care organisations, industry and the general public should work together to combat overweight and obesity. The chances of success are not predictable but are certainly big enough to justify action.


Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women.
Triple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type. In this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women. Tumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes. Expression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome. Stromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC.


Sequence analysis for assessing potential allergenicity.
Sequence analysis plays an important role in assessing the potential allergenicity of proteins used in transgenic foods, particularly for proteins that have not previously been part of the food supply. Sequence comparisons are used to indicate potential unexpected cross reactivity to existing allergens and to assess the potential for developing new sensitivities. Although the concept of using sequence analysis is straightforward, implementing a bioinformatic analysis that is accurate and complete can be complex. Several factors need to be considered, including the design and content of the sequence database, the analysis strategy, and the criteria for evaluating the results.


Stepwise progression of B cell malignancy occurred in a bone marrow stromal cell-dependent pre-B cell clone.
The murine long-term bone marrow culture system which can support the almost infinite growth of normal B lineage cells was used to establish the experimental model for spontaneous B cell leukemogenesis. At the early phase of the culture, B cell differentiation with diversification of immunoglobulin genes was induced. However, the culture was finally captured by a single B cell clone which had the fastest growth rate. The B cell clone was strictly dependent on stromal cells for in vitro growth and did not generate leukemia when injected into syngenic mice. After up to a year of maintenance of the clone, the leukemic cells developed spontaneously. The leukemic cell line isolated in vivo retained the stromal cell-dependency, and further in vitro selection process was required to establish the stromal cell-independent leukemic cell line. These leukemic cell lines highly expressed c-myc and Ha-ras genes regardless of stromal cell-dependency. We detected no chromosomal aberrations accompanied with the process of leukemic transformation. Our results suggest that spontaneous neoplastic transformation of B cells in long-term bone marrow culture occurs in a stepwise manner.


Temperature probing and emission color tuning by morphology and size control of upconverting β-NaYb0.67Gd0.30F4:Tm0.015:Ho0.015 nanoparticles.
The chemical composition, shape and size of upconverting nanoparticles are known to have a great influence on their spectroscopic properties, such as the emission color and the emission intensity variation as a function of temperature. This work shows the color tuning and the thermal sensitivity of NaYb0.67Gd0.30F4:Tm0.015:Ho0.015 nanoparticles synthesized by two different approaches of the same synthetic method showing the influence of size and morphology, 250 nm hexagonal-plated and 30 nm spheroidal nanoparticles, on the visible upconversion color under NIR irradiation. According to the 1931-CIE diagram, the hexagonal-shaped nanoparticles show white light emission and the spheroidal ones generate red light emission under 980 nm excitation. Besides, the variation of the luminescence intensity ratio of Tm3+ emissions as a function of temperature was monitored in the 77-293 K temperature range, and the maximum relative sensitivity (Sm) of the samples reached 1.33% K-1 for the hexagonal-plated nanoparticles and 1.76% K-1 for the spheroidal nanoparticles. These maximum sensitivity values are higher compared to the ones found in the literature for temperature sensing using upconverting nanoparticles. These data suggest the versatility of these nanoparticles for applications on white light emission and nanothermometry.


[Impact of biochemisty on the duration of treatment for pulmonary embolus].
Can the biochemical evidence for "new thrombophilic factors" influence the duration of AVK treatment following the occurrence of a first pulmonary embolus? Certainly for the classic but very rare antithrombin defects as well as for the existence of circulating anticoagulant. Possibly for protein C and S defects. On the other hand, the existence of a heterozygotic "Leiden" mutation of factor V, or factor II, and an increase of factors VIII, IX, or XI, do not at present warrant a change in AVK prescription. In effect, in the case where the existence of a thrombogenic state implies a prolongation of AVK treatment with its significant potential complications, it is indispensable that the risk/benefit ratio is well founded, which is not the case for these "new" thrombophilic states. The coexistence of several of these new biochemical anomalies (for example the association of a factor V and factor II mutation) probably represents an excess risk of thrombosis, but in this situation the reasoning remains the same. On the other hand, faced with a confirmed recurrence, the studies in the literature tell us that very long term treatment should be debated independently from the biochemical results. It is conceivable that there are biochemical anomalies (sometimes quite frequent which should be viewed as "normal variants") which, although they have great significance for improving the understanding of venous thrombo-embolic disease, do not at present warrant a change in our therapeutic protocols. Another facet of the problem concerns the use of D-dimers following the first months of AVK treatment in order to possibly distinguish patients at low risk of recurrence. The first results of this approach are interesting, but require confirmation before they can be used in practice.


Effects of metronidazole analogues on Giardia lamblia: experimental infection and cell organization.
The chemotherapeutic agents used for the treatment of giardiasis are often associated with adverse side effects and are refractory cases, due to the development of resistant parasites. Therefore the search for new drugs is required. We have previously reported the giardicidal effects of metronidazole (MTZ) and its analogues (MTZ-Ms, MTZ-Br, MTZ-N(3), and MTZ-I) on the trophozoites of Giardia lamblia. Now we evaluated the activity of some giardicidal MTZ analogues in experimental infections in gerbils and its effects on the morphology and ultrastructural organization of Giardia. The giardicidal activity in experimental infections showed ED(50) values significantly lower for MTZ-I and MTZ-Br when compared to MTZ. Transmission electron microscopy was employed to approach the mechanism(s) of action of MTZ analogues upon the protozoan. MTZ analogues were more active than MTZ in changing significantly the morphology and ultrastructure of the parasite. The analogues affected parasite cell vesicle trafficking, autophagy, and triggered differentiation into cysts. These results coupled with the excellent giardicidal activity and lower toxicity demonstrate that these nitroimidazole derivates may be important therapeutic alternatives for combating giardiasis. In addition, our results suggest a therapeutic advantage in obtaining synthetic metronidazole analogues for screening of activities against other infectious agents.


Suture Anchor Repair of Pectoralis Major Muscle Dehiscence After Modified Ravitch.
During repair of pectus excavatum by the modified Ravitch procedure, the major pectoral muscles are detached from their sternal insertion to obtain adequate surgical exposure. Following repair, the muscles are approximated in midline and reinserted through scarring. Dehiscence of the major pectoral muscles after the modified Ravitch procedure is a rare phenomenon, not previously reported in literature. We report on 2 cases and describe an effective treatment method using sternal suture anchors with good long-term results.


Risk factors of cesarean delivery at prenatal care, admission and during labor in low-risk pregnancy: multivariate logistic regression analysis.
Risk assessment for cesarean delivery is not a one-time assessment, but rather a procedure that continues throughout pregnancy and labor. The objective of this study was to develop models to determine risk factors of cesarean delivery in three stages in low-risk pregnancy. The period from pregnancy to childbirth was divided into three stages, including prenatal care, admission and labor. Multivariable logistic regression analysis was used to develop three risk assessment models according to these stages, which were compared by areas under receiver operating characteristic (ROC) curves. We developed three predictive models with different risk factors. The ability of each model to determine the risk of cesarean delivery differed according to the three stages. The ROC curve values differed significantly between the labor (model III) and prenatal care (model I) or admission (model II) models (z=11.43, P<0.001; z=8.18, P<0.001, respectively). There was also a difference in the ROC between models I and II (z=6.76, P<0.001). This study shows that the models constructed for the more advanced stages of pregnancy were the more accurate risk factors of cesarean delivery. Therefore, the risk assessment model for cesarean delivery should be differently adapted according to each stage.


Factors associated with hysterectomy among older women from Latin America and the Caribbean.
To identify factors associated with hysterectomy, data collected from 1999-2000 were assessed from seven cities of the Health, Well-Being and Aging in Latin America and the Caribbean Study on 6,549 women, aged 60 years and older. Hysterectomy prevalence ranged from 12.8% in Buenos Aires (Argentina) to 30.4% in Bridgetown (Barbados). The median age for having had a hysterectomy ranged from 45 to 50 years across the cities and was 47 years in the pooled sample. Ethnic differences in hysterectomy rates were partially explained by differences across cities. Factors significantly associated with lower odds for hysterectomy included older age, household crowding conditions, and having public/military or no health insurance, compared to having private health insurance. Women who had three or more children were less likely to have had a hysterectomy, a finding that differs from most previous studies. Socioeconomic position related to rates of hysterectomy in late life rather than hysterectomies earlier in life. However, the nature of these differences varied across birth cohorts. The findings suggested that adverse socioeconomic factors were most likely related to hysterectomy risk by affecting access to health care, whereas parity was most likely acting through an effect on decision-making processes.


Acute oral captopril inhibits angiotensin converting enzyme activity in human cerebrospinal fluid.
Angiotensin converting enzyme (ACE) activity in human plasma and cerebrospinal fluid (CSF), was measured by a fluorimetric method, following an acute oral dose (75 mg) of captopril. A decrease of approximately 60% in enzyme activity was observed in CSF, suggesting that the drug penetrates the blood/brain barrier (BBB) in sufficient amounts to inhibit the ACE in CSF. The activity of CSF enkephalinase, an enzyme present in human brain and inhibited in vitro by an elevated concentration of captopril, was, however, unaffected by the acute drug administration. It is proposed that the antihypertensive effect of captopril in humans may be due, at least in part, to the inhibition of ACE contained within brain structures.


[Effect of cholera enterotoxin on carbohydrate metabolism of the liver and small intestine mucosa in the rabbit].
Changes in carbohydrate metabolism were studied in the isolated intestinal loops of rabbits during secretory diarrhea, induced by cholera enterotoxin. Glucose synthesis level in the small intestinal mucosa and liver was measured by isotope technique, using L-alanine as a precursor. Intestinal gluconeogenesis, calculated per mg of protein, appeared to be twice higher than in the liver of fasting rabbits. Cholera enterotoxin administration enhanced gluconeogenesis in the liver by 60%, as compared to the control. The rate of glucose synthesis and glucose-6-phosphatase activity in the intestinal mucosa remained unchanged, whereas glucose-6-phosphatase in the liver was slightly inhibited. It is suggested that gluconeogenesis in the liver supplies glucose as a convenient energy source for the secretory process induced by cholera enterotoxin in the rabbit small intestine.


Thermolysin activation mutants with changes in the fusogenic region of an influenza virus hemagglutinin.
Influenza virus A/seal/Mass/1/80 (H7N7) mutants were obtained; the hemagglutinins (HAs) of the mutants were not activated by trypsin, as in the wild-type virus, but by thermolysin. The mutants grew efficiently under multiple replication cycle conditions and formed plaques in chicken embryo cells only when thermolysin was added to the culture medium. They exhibited hemolytic activity and induced protective immunity in chickens after an asymptomatic course of infection. Nucleotide sequencing of the HA gene and direct amino acid sequencing showed that insertion of a single leucine into the fusion peptide of the HA2 chain close to the cleavage site and a shift of the cleavage site toward the C terminus by one amino acid were responsible for the changes in the biological properties of the thermolysin activation mutants. Revertants could be obtained when trypsin or trypsin-like endoproteases were present in the virus-producing system.


In vitro antibacterial and antifungal activity of salicylanilide benzoates.
The resistance to antimicrobial agents brings a need of novel antimicrobial agents. We have synthesized and found the in vitro antibacterial activity of salicylanilide esters with benzoic acid (2-(phenylcarbamoyl)phenyl benzoates) in micromolar range. They were evaluated in vitro for the activity against eight fungal and eight bacterial species. All derivatives showed a significant antibacterial activity against Gram-positive strains with minimum inhibitory concentrations ≥ 0.98 μmol/L including methicillin-resistant Staphylococcus aureus strain. The most active compounds were 5-chloro-2-(3,4-dichlorophenylcarbamoyl)phenyl benzoate and 4-chloro-2-(4-(trifluoromethyl)phenylcarbamoyl)phenyl benzoate. The antifungal activity is significantly lower.


Polymer as an Additive in the Emitting Layer for High-Performance Quantum Dot Light-Emitting Diodes.
A facile but effective method is proposed to improve the performance of quantum dot light-emitting diodes (QLEDs) by incorporating a polymer, poly(9-vinlycarbazole) (PVK), as an additive into the CdSe/CdS/ZnS quantum dot (QD) emitting layer (EML). It is found that the charge balance of the device with the PVK-added EML was greatly improved. In addition, the film morphology of the hole-transporting layer (HTL) which is adjacent to the EML, is substantially improved. The surface roughness of the HTL is reduced from 5.87 to 1.38 nm, which promises a good contact between the HTL and the EML, resulting in low leakage current. With the improved charge balance and morphology, a maximum external quantum efficiency (EQE) of 16.8% corresponding to the current efficiency of 19.0 cd/A is achievable in the red QLEDs. The EQE is 1.6 times as high as that (10.5%) of the reference QLED, comprising a pure QD EML. This work demonstrates that incorporating some polymer molecules into the QD EML as additives could be a facile route toward high-performance QLEDs.


Starvation-induced cross protection against heat or H2O2 challenge in Escherichia coli.
Glucose- or nitrogen-starved cultures of Escherichia coli exhibited enhanced resistance to heat (57 degrees C) or H2O2 (15 mM) challenge, compared with their exponentially growing counterparts. The degree of resistance increased with the time for which the cells were starved prior to the challenge, with 4 h of starvation providing the maximal protection. Protein synthesis during starvation was essential for these cross protections, since chloramphenicol addition at the onset of starvation prevented the development of thermal or oxidative resistance. Starved cultures also demonstrated stronger thermal and oxidative resistance than did growing cultures adapted to heat, H2O2, or ethanol prior to the heat or H2O2 challenge. Two-dimensional gel electrophoresis of 35S-pulse-labeled proteins showed that subsets of the 30 glucose starvation proteins were also synthesized during heat or H2O2 adaptation; three proteins were common to all three stresses. Most of the common proteins were among the previously identified Pex proteins (J.E. Schultz, G. I. Latter, and A. Matin, J. Bacteriol. 170:3903-3909, 1988), which are independent of cyclic AMP positive control for their induction during starvation. Induction of starvation proteins dependent on cyclic AMP was not important in these cross protections, since a delta cya strain of E. coli K-12 exhibited the same degree of resistance to heat or H2O2 as the wild-type parent did during both growth and starvation.


Comparison of surface emissions and subsurface distribution of cis- and trans-1,3-dichloropropene and chloropicrin in sandy field beds covered with four different plastic films.
The purpose of this study was to conduct a field study at a Florida field site on surface emissions and subsurface distribution of cis-and trans-1,3-dichloropropene (1,3-D) and chloropicrin (CP) in raised beds injected with Telone C35 with four replications. A total of 16 beds were applied with Telone C35 by chisel injection and covered with four different plastic films, 4 beds for each film. Each bed was installed with five 20-cm long soil pore air probes and a surface air collection pan at arbitrarily locations along the length of each bed for sampling soil pore air and surface air, respectively, for analysis of the three biologically active compounds, cis- and trans-1,3-D and CP. We found that average concentrations of the three compounds at 20-cm depth among the beds covered with four different plastic films generally were not statistically different. Among the four beds covered with the same plastic film, average concentrations of the three compounds were statistically different only in the four metallic PE covered beds at 5 and 24 hours after injection. Volatilization rates of the three compounds among the beds covered with four different plastic films, with the exception of CP at 48 hours after injection, were not statistically different. It appeared that initial upward diffusion and volatilization flux were influenced by solar radiation. Initial subsurface concentrations of the three compounds and volatilization flux, especially cis-1,3-D, were greater in the beds on the east side of the field than that in the beds on the west side of the field. Whether or not difference in initial subsurface concentrations of the compounds between east side beds and west side beds may influence fumigant efficacy remains to be determined.


Enzymatic synthesis and in vitro evaluation of folate-functionalized liposomes.
In this study, folate-poly(ethylene glycol)3400-cholesterol conjugates (FA-PEG-Chol) were enzymatically synthesized in one step and incorporated into liposomes to prepare folate (FA)-functionalized liposomes for targeted drug delivery. The FA-functionalized liposomes loaded with betulinic acid (BA) (FA-L-BA) were prepared by thin lipid film method. The FA-L-BA was characterized by their morphology, particle size, zeta potential, encapsulation efficiency (EE), stability, cell cytotoxicity and cellular uptake. The average size of FA-L-BA was 222±8 nm. The spherical particles exhibited a negative electrical charge of -20.12±1.45 mV and high EE of 91.61%±1.16%. The liposomes were taken up selectively by HepG2 cells. FA-L-BA showed enhanced cytotoxicity (50% inhibitory concentration [IC50] =63.07±2.22 μg/mL) compared to nontargeted control normal liposomes loaded with BA (L-BA; IC50 =93.14±2.19 μg/mL) in HepG2 cells in vitro. In addition, FA-functionalized liposomes loaded with Ir-1 (FA-L-Ir-1) showed significantly higher cellular uptake in HepG2 cells compared to nontargeted control normal liposomes loaded with Ir-1 (L-Ir-1). This novel approach for the liposomes surface modified with FA by a one-step enzymatic amidation was expected to provide potential application as a drug carrier for active targeted delivery to tumor cells.


Anorexia nervosa and comorbid autism spectrum disorders.
Traits of autism spectrum disorder (ASD) are overrepresented among individuals with anorexia nervosa (AN) and may also moderate the behavioral manifestation of AN. This review aims to provide an overview of AN and comorbid ASD. Elevated ASD traits do not seem to precede AN among some individuals but are rather related to the illness stage. However, studies have suggested that there are ASD-specific mechanisms for developing AN in a subgroup of individuals with AN. Pronounced traits of ASD and diagnosed ASD are associated with illness prolongation and poorer outcomes in AN, and individuals with AN and elevated ASD traits may benefit less from many of the current treatments. Studies do not support a specific genetic relationship between ASD and AN. Recent research encourages the improved recognition of elevated ASD traits in individuals with AN and provides grounds for developing tailored treatments for those with this comorbidity.


Perceived risk of work-related injury and intentions to change employment.
A survey of 263 employed men and women examined the effect of length of employment, perceived ability to find a better job, positive job features (pay, job security, and intrinsic interest), and perceived risk of occupational injury on intentions to stay with or leave one's current employer. Perceived risk of occupational injury significantly predicted one's belief that the person would not stay with the current employer. Perceived inability to find alternative employment lessened the desirability of leaving the current employer. Desire to leave was lower when a job was rated highly for pay, security, and intrinsic interest. Length of employment, as a measure of job commitment, was not a factor.


Safe Reinforcement Learning With Stability Guarantee for Motion Planning of Autonomous Vehicles.
Reinforcement learning with safety constraints is promising for autonomous vehicles, of which various failures may result in disastrous losses. In general, a safe policy is trained by constrained optimization algorithms, in which the average constraint return as a function of states and actions should be lower than a predefined bound. However, most existing safe learning-based algorithms capture states via multiple high-precision sensors, which complicates the hardware systems and is power-consuming. This article is focused on safe motion planning with the stability guarantee for autonomous vehicles with limited size and power. To this end, the risk-identification method and the Lyapunov function are integrated with the well-known soft actor-critic (SAC) algorithm. By borrowing the concept of Lyapunov functions in the control theory, the learned policy can theoretically guarantee that the state trajectory always stays in a safe area. A novel risk-sensitive learning-based algorithm with the stability guarantee is proposed to train policies for the motion planning of autonomous vehicles. The learned policy is implemented on a differential drive vehicle in a simulation environment. The experimental results show that the proposed algorithm achieves a higher success rate than the SAC.


Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3.
A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3.


CT-guided sacroplasty for the treatment of sacral insufficiency fractures.
To describe the clinical presentation, procedure and outcome in patients treated with computed tomography (CT)-guided sacroplasty as a treatment for sacral insufficiency fractures. Three patients (mean age 80 years, range 75-87 years) were treated with CT-guided sacroplasty. The mean pre-procedure visual analogue score (VAS) for pain was 8 (range 7-9) with a mean symptom duration of 8 months (range 2.5-18). The procedure was performed under CT guidance with needles being placed along the fracture lines from a posterior approach. Polymethylmethacrylate (PMMA) cement was introduced in 0.2 ml aliquots after cement temperature reduction. Cement injection was monitored by four-section block axial acquisition to assess potential cement migration. All three procedures were performed without significant complication. One patient developed a tiny asymptomatic cement leak into the S1 foramen. The mean volume of cement injected into a unilateral sacral fracture was 4 ml. All patients tolerated the procedure well under intravenous sedation. The mean VAS score post-procedure was 2. Continued symptomatic relief was seen at 6 weeks and 3 months. CT-guided sacroplasty represents an alternative treatment for sacral insufficiency fractures that are resistant to conservative treatment. The symptomatic relief the procedure produces seems to be excellent both in this small series and in described cases in the literature.


Systematic Engineering on Ni-Based Nanocatalysts Effectively Promote Hydrogen Evolution Reaction.
Designing a synthesis of ultra-small Ni-based nanomaterials with high intrinsic activity and stability in alkaline hydrogen evolution reaction (HER) is a major challenge. Herein, a series of noble metal doped ultra-small size (4 nm) M-Ni/NiO nanoparticles supported on CNT are rationally designed by a solvent-free microwave reduction method that is fast (60 s), simple, includes no surfactants, extensive (>1 g), and has high yield (82.7%). The Ir-Ni/NiO@CNT has superior performance with a low overpotential of 24.6 mV at 10 mA cm-2 . In addition, the turnover frequency (TOF) value up to 2.51 s-1 and the exchange current density reaches 4.34 mA cm-2 , indicating that the catalyst has better intrinsic catalytic activity. It is further proved by density functional theory (DFT) that the NiO surface is conducive to the adsorption of OH* in the Volmer step while the Ni is inclined to adsorb H*, which synergistically promotes the water-splitting reaction, thereby increasing the catalytic rate of HER. It is believed that this work will provide valuable contributions and inspirations toward the large-scale production of high-performance Ni-based electrocatalysts for HER.


Two cases of bilateral reverse shoulder arthroplasty performed in patients with rheumatoid arthritis.
Bilateral shoulder joint disorders caused by rheumatoid arthritis significantly impair daily functioning owing to a lack of contralateral compensation. In Japan, reverse shoulder joint prostheses were approved in 2014. This was expected to improve the surgical outcomes of rheumatoid shoulder arthroplasty. We report two patients with rheumatoid arthritis who underwent bilateral reverse shoulder arthroplasty. This study aims to evaluate their postoperative clinical outcomes and activities of daily living. The patients were women in their 70s with stage III class 2 rheumatoid arthritis. Their treatment and postoperative activities of daily living were retrospectively reviewed. The first patient underwent the inlay type and experienced a residual limitation of external rotation postoperatively; therefore, she was restricted to dress with front-open clothes. However, she was able to undress after the lining of the garment was changed to a slippery material. The second patient underwent the onlay type and showed almost no limitations in postoperative activities of daily living. She was able to undress with an external rotation of 40-50°. Bilateral reverse shoulder arthroplasty improved range of motion, the Japanese Orthopaedic Association shoulder score, and functional outcomes. Only a few difficulties were encountered in the activities of daily living.


[Consumption of white wine retards development of atherosclerosis and affects anticoagulation].
An inverse relationship between moderate alcohol use and coronary heart disease was found in various countries. Aims of the study were to find out whether drinking of moravian white wine will have the same effect on lipoproteins and fibrinogen as described in foreign wines. Blood pressure, body mass, blood glucose and a hepatic enzyme were also measured before and after drinking. Drinking of the Moravian white wine (vintage 1999; alcohol 11.48 vol %) was studied in 50 men aged 44.4 (SD 9.25) years. Drinking of 350 ml (40.2 g of alcohol) every evening for four weeks without any change of dietary factors followed in 45 men by statistically significant increase in HDL cholesterol from 1.17 to 1.25 mmol/l (p < 0.001) and free HDL cholesterol from 0.17 to 0.20 mmol/l (p < 0.0001) and highly significant (p < 0.00001) decrease in plasma fibrinogen level from 3.77 to 3.35 g/l. Nor triglycerides, or blood glucose and BMI were changed after increasing source of carbohydrates in wine. Mean systolic blood pressure of 123.4 mmHg did not change and diastolic blood pressure decreased insignificantly from 78.0 to 76.7 mmHg. Minimal decrease of ALT from 0.60 to 0.59 mukat/l disproved any hepatic disturbance. Everynight moderate drinking of Moravian white wine has similar beneficial effect as consumption of foreign alcohol drinks.