Nuclease-assisted suppression of human DNA background in sepsis.
Sepsis is a severe medical condition characterized by a systemic inflammatory response of the body caused by pathogenic microorganisms in the bloodstream. Blood or plasma is typically used for diagnosis, both containing large amount of human DNA, greatly exceeding the DNA of microbial origin. In order to enrich bacterial DNA, we applied the C0t effect to reduce human DNA background: a model system was set up with human and Escherichia coli (E. coli) DNA to mimic the conditions of bloodstream infections; and this system was adapted to plasma and blood samples from septic patients. As a consequence of the C0t effect, abundant DNA hybridizes faster than rare DNA. Following denaturation and re-hybridization, the amount of abundant DNA can be decreased with the application of double strand specific nucleases, leaving the non-hybridized rare DNA intact. Our experiments show that human DNA concentration can be reduced approximately 100,000-fold without affecting the E. coli DNA concentration in a model system with similarly sized amplicons. With clinical samples, the human DNA background was decreased 100-fold, as bacterial genomes are approximately 1,000-fold smaller compared to the human genome. According to our results, background suppression can be a valuable tool to enrich rare DNA in clinical samples where a high amount of background DNA can be found.


Soluble P2X7 Receptor Plasma Levels in Obese Subjects before and after Weight Loss via Bariatric Surgery.
Obesity is a systemic disease frequently associated with important complications such as type 2 diabetes and cardiovascular diseases. It has also been proven that obesity is a disease associated with chronic low-grade systemic inflammation and that weight loss improves this low-grade chronic inflammatory condition. The P2X7 purinergic receptor (P2X7R), belonging to the family of the receptors for extracellular ATP, is a main player in inflammation, activating inflammasome and pro-inflammatory cytokine production. In this study, we evaluated the plasma levels of soluble P2X7R (sP2X7R) measured in a group of obese patients before and one year after bariatric surgery. Furthermore, we evaluated the relation of sP2X7R to inflammatory marker plasma levels. We enrolled 15 obese patients who underwent laparoscopic sleeve gastrectomy, evaluating anthropometric parameters (weight, height, BMI and waist circumference) before and after surgery. Moreover, we measured the plasma levels of inflammatory markers (CRP, TNFα and IL-6) before and after weight loss via bariatric surgery. The results of our study show that one year after bariatric surgery, obese patients significantly decrease body weight with a significant decrease in CRP, TNF-alfa and IL-6 plasma levels. Similarly, after weight loss, obese subjects showed a significant reduction in sP2X7R plasma levels. Moreover, before surgery, plasma levels of sP2X7R were inversely related with those of CRP, TNF-alfa and IL-6. Given the role of P2X7R in inflammation, we hypothesized that, in obese subjects, sP2X7R could represent a possible marker of chronic low-grade inflammation, hypothesizing a possible role as a mediator of obesity complications.


DRUG MISUSE AND SELF-MEDICATION AMONG PHARMACY STUDENTS IN JORDAN.
Aim: To estimate risks and prevalence of self-medication and potential abuse risk among pharmacy students in Jordanian Universities. Materials and Methods: A cross-sectional study design was conducted with 450 students, selected using multistage sampling methods, from seven different universities. Data was collected by self-administrated questionnaires covering demographic and academic information, health-related information, use of self-medication, and pattern of self-medication among pharmacy students. Results: Out of 394 students who answer the questions, 76.9% reported that they had usually treated themselves in case of simple cases without physician or pharmacist consultation. Most commonly used drugs among the surveyed students were Paracetamol 60%, multivitamins supplement 74.25%, and herbal products 37.2%, combination of NSAIDs and Paracetamol 20.6%, and laxatives 19.4%. Cold and flu 25.5%, headache 22.3%, abdominal pain 7.9%, gastric pain 7.9%, cold and flu, headache, abdominal pain, and gastric pain 14.9% were the main conditions which contribute to self-medication practice. It was also found that Pharmacy students were over-confident with the type of cases they could treat without referral to a specialist physician, despite knowing that some of the symptoms may be due to serious health problems. Misuse of analgesics and laxatives was clear, and there was a weakness in knowledge of the indications for the use of the most common drug. Conclusions: The prevalence of self-medication among pharmacy students in Jordan is high, and medical teaching institutions need to educate students about the proper use of medicines. Strict legislation and more education on self-medication are necessary for effective use of medicines.


A Psychosocial Genomics Pilot Study in Oncology for Verifying Clinical, Inflammatory and Psychological Effects of Mind-Body Transformations-Therapy (MBT-T) in Breast Cancer Patients: Preliminary Results.
Several studies have highlighted the key role of chronic inflammation in breast cancer development, progression, metastasis, and therapeutic outcome. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation. Recent findings suggest that positive psychosocial experiences, including psychotherapeutic interventions and therapeutic mind-body protocols, can modulate the inflammatory response by reducing the expression of genes/proteins associated with inflammation and stress-related pathways. Our preliminary results indicate that a specific mind-body therapy (MBT-T) could induce a significant reduction of the release of different cytokines and chemokines, such as SCGFβ, SDF-1α, MCP3, GROα, LIF, and IL-18, in the sera of breast cancer patients compared to a control group, suggesting that MBT-T could represent a promising approach to improve the wellness and outcome of breast cancer patients.


Androgen-independent prostate cancer cells acquire the complete steroidogenic potential of synthesizing testosterone from cholesterol.
The proliferation and differentiation of normal prostate epithelial cells depends upon the action of androgens produced by the testis. Prostate cancers retain the ability to respond to androgens in the initial stages of cancer development, but progressively become independent of exogenous androgens in advanced stages of the disease while maintaining the expression of functional androgen receptor (AR). In the present study, we have determined the potential of prostate cancer cells to synthesize androgens from cholesterol which may be involved in intracrine regulation of AR in advanced stages of the disease. Established androgen-independent prostate cancer cell lines, PC3 and DU145 cells, expressed mRNA and proteins for scavenger receptor type B1 (SRB1), steroidogenic acute regulatory (StAR) protein, cytochrome P450 cholesterol side chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and other enzymes involved in androgen biosynthesis. Expression of all these proteins and enzymes was significantly higher in the androgen-independent derivative of LNCaP prostate cancer cells (C81) than in the androgen-dependent cell line (C33). In serum-free cultures, the androgen-independent C81 cells secreted approximately 5-fold higher testosterone than C33 cells as determined in the conditioned media by immunoassays. These cells could also directly convert radioactive cholesterol into testosterone which was identified by thin layer chromatography. These results for the first time show that prostate cancer cells in advanced stages of the disease could synthesize androgens from cholesterol and hence are not dependent upon testicular and/or adrenal androgens.


Treatment principles for coccygodynia.
An evaluation of treatment methods and outcomes for coccygodynia cases that do not respond to conservative treatment. Local anesthetic and steroid injections were applied in 32 coccygodynia cases that did not respond to conservative treatment (average of 15 months). Coccyx excision was performed as surgical treatment in 25 cases that had pain relief after the injections but later re-presented with complaints. The patients' pain levels were assessed with VAS. Postacchini classification was used for patient classification based on plain radiography. 20 (62%) of the cases (the total including injection and surgery groups) had a trauma history. Majority of the cases treated with local steroid injection included patients with Type I, while the 25 cases that received surgical treatment predominantly included Type II patients. One case had post-operative skin infection, which was treated with antibiotics. It was observed by comparing pre-operative and post-operative pain scores that both methods provided significant pain relief in all patients. While local steroid injection is an effective method of treatment for Type I patients, the coccyx removal is an effective method for controlling the pain in patients with trauma history and in Type II, III and IV patients.


Effect of enzymic (collagenase) harvesting on the intracellular Na+/K+ ratio of Swiss/3T3 cells as revealed by X-ray microanalysis.
Swiss/3T3 cell cultures were harvested with 0.05% collagenase and after centrifugation the pellet was prepared by the freeze-fracture/freeze-drying (FFFD) method for bulk-specimen X-ray microanalysis. Time-dependent variations in the intracellular monovalent elemental concentrations (Na+, K+ and Cl-) as well as of the Na+/K+ ratio were followed for 120 min subsequent to harvesting. The quantitative measurements revealed a very considerable increase in the intracellular Na+ and Cl- accompanied by a decrease in the K+ concentration as soon as 5 min after harvesting. The Na+/K+ ratio had increased by this time to about 1.5 on average. These changes indicate a sustained depolarization of the cell membrane. During the first 60 min this depolarization tended to normalize as demonstrated by an exponential decrease in the intracellular Na+ and Cl- and an increase in the K+ content involving a decrease in the Na+/K+ ratio. The total intracellular monovalent ion concentration remained almost constant during this post-harvesting period. These results suggest that harvesting represents a serious depolarizing stimulus to the cells, the consequences of which are restored only after 1-2h. These alterations should be taken into consideration during various experimental designs when using anchorage-dependent cell cultures.


Excess morbidity and mortality in patients with craniopharyngioma: a hospital-based retrospective cohort study.
Most studies in patients with craniopharyngioma did not investigate morbidity and mortality relative to the general population nor evaluated risk factors for excess morbidity and mortality. Therefore, the objective of this study was to examine excess morbidity and mortality, as well as their determinants in patients with craniopharyngioma. Hospital-based retrospective cohort study conducted between 1987 and 2014. We included 144 Dutch and 80 Swedish patients with craniopharyngioma identified by a computer-based search in the medical records (105 females (47%), 112 patients with childhood-onset craniopharyngioma (50%), 3153 person-years of follow-up). Excess morbidity and mortality were analysed using standardized incidence and mortality ratios (SIRs and SMRs). Risk factors were evaluated univariably by comparing SIRs and SMRs between non-overlapping subgroups. Patients with craniopharyngioma experienced excess morbidity due to type 2 diabetes mellitus (T2DM) (SIR: 4.4, 95% confidence interval (CI): 2.8-6.8) and cerebral infarction (SIR: 4.9, 95% CI: 3.1-8.0) compared to the general population. Risks for malignant neoplasms, myocardial infarctions and fractures were not increased. Patients with craniopharyngioma also had excessive total mortality (SMR: 2.7, 95% CI: 2.0-3.8), and mortality due to circulatory (SMR: 2.3, 95% CI: 1.1-4.5) and respiratory (SMR: 6.0, 95% CI: 2.5-14.5) diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence were identified as risk factors for excess T2DM, cerebral infarction and total mortality. Patients with craniopharyngioma are at an increased risk for T2DM, cerebral infarction, total mortality and mortality due to circulatory and respiratory diseases. Female sex, childhood-onset craniopharyngioma, hydrocephalus and tumour recurrence are important risk factors.


A technique for bioinstrumentation of the thorax of miniature swine.
A surgical technique for sternal thoracotomy was developed for use in miniature swine. An incision was made from the midpoint of the neck to the tip of the xiphoid cartilage. The thorax was entered by dividing the sternum along its long axis with an electric oscillating saw. The thoracotomy was closed with 3-mm wide polyester fiber umbilical tapes placed around each sternebrae to appose the cut surfaces. The technique provided good access to the cranial vena cava, both atria and appendages, both ventricles, great cardiac veins, coronary sinus, ascending aorta and arch, and the pulmonary artery. Miniature swine tolerated this procedure well. It appeared to be less painful than lateral approaches and produced fewer pleural adhesions because only the mediastinum was entered.


Equivalent Hypertrophy and Strength Gains in β-Hydroxy-β-Methylbutyrate- or Leucine-supplemented Men.
Ingestion of proteins with high leucine content during resistance training (RT) can augment hypertrophy. Some data suggest that a leucine metabolite, β-hydroxy, β-methylbutyrate (HMB), is substantially more anabolically efficacious than leucine. We aimed to test whether supplementation with HMB versus leucine, added to whey protein, would result in differential muscle hypertrophy and strength gains in young men performing RT. Twenty-six resistance-trained men (23 ± 2 yr) performed 12 wk of RT with three phases. Phase 1: 8 wk of periodized RT (three training sessions per week). Phase 2: 2 wk overreaching period (five sessions per week). Phase 3: 2 wk taper (three sessions per week). Participants were randomly assigned to twice daily ingestion of: whey protein (25 g) plus HMB (1.5 g) (whey+HMB; n = 13) or whey protein (25 g) plus leucine (1.5 g) (whey+leu; n = 13). Skeletal muscle biopsies were performed before and after RT. Measures of fat- and bone-free mass, vastus lateralis (VL) muscle thickness and muscle cross-sectional area (CSA) (both by ultrasound), muscle fiber CSA, and 1-repetition maximum (1-RM) strength tests were determined. We observed increases in fat- and bone-free mass, VL muscle thickness, muscle CSA and fiber type CSA and 1-RM strength with no differences between groups at any phase. We observed no differences between groups or time-group interactions in hormone concentrations at any phase of the RT program. β-Hydroxy-β-methylbutyrate added to whey did not result in greater increases in any measure of muscle mass, strength, or hormonal concentration compared to leucine added to whey. Our results show that HMB is no more effective in stimulating RT-induced hypertrophy and strength gains than leucine.


Innate immunity to Mycobacterium tuberculosis.
The different manifestations of infection with Mycobacterium tuberculosis reflect the balance between the bacillus and host defense mechanisms. Traditionally, protective immunity to tuberculosis has been ascribed to T-cell-mediated immunity, with CD4(+) T cells playing a crucial role. Recent immunological and genetic studies support the long-standing notion that innate immunity is also relevant in tuberculosis. In this review, emphasis is on these natural, innate host defense mechanisms, referring to experimental data (e.g., studies in gene knockout mice) and epidemiological, immunological, and genetic studies in human tuberculosis. The first step in the innate host defense is cellular uptake of M. tuberculosis, which involves different cellular receptors and humoral factors. Toll-like receptors seem to play a crucial role in immune recognition of M. tuberculosis, which is the next step. The subsequent inflammatory response is regulated by production of pro- and anti-inflammatory cytokines and chemokines. Different natural effector mechanisms for killing of M. tuberculosis have now been identified. Finally, the innate host response is necessary for induction of adaptive immunity to M. tuberculosis. These basic mechanisms augment our understanding of disease pathogenesis and clinical course and will be of help in designing adjunctive treatment strategies.


Phenylpropanoid Biosynthesis Gene Expression Precedes Lignin Accumulation During Shoot Development in Lowland and Upland Switchgrass Genotypes.
Efficient conversion of lignocellulosic biomass into biofuels is influenced by biomass composition and structure. Lignin and other cell wall phenylpropanoids, such as para-coumaric acid (pCA) and ferulic acid (FA), reduce cell wall sugar accessibility and hamper biochemical fuel production. Toward identifying the timing and key parameters of cell wall recalcitrance across different switchgrass genotypes, this study measured cell wall composition and lignin biosynthesis gene expression in three switchgrass genotypes, A4 and AP13, representing the lowland ecotype, and VS16, representing the upland ecotype, at three developmental stages [Vegetative 3 (V3), Elongation 4 (E4), and Reproductive 3 (R3)] and three segments (S1-S3) of the E4 stage under greenhouse conditions. A decrease in cell wall digestibility and an increase in phenylpropanoids occur across development. Compared with AP13 and A4, VS16 has significantly less lignin and greater cell wall digestibility at the V3 and E4 stages; however, differences among genotypes diminish by the R3 stage. Gini correlation analysis across all genotypes revealed that lignin and pCA, but also pectin monosaccharide components, show the greatest negative correlations with digestibility. Lignin and pCA accumulation is delayed compared with expression of phenylpropanoid biosynthesis genes, while FA accumulation coincides with expression of these genes. The different cell wall component accumulation profiles and gene expression correlations may have implications for system biology approaches to identify additional gene products with cell wall component synthesis and regulation functions.


Cross-species infection of specific-pathogen-free pigs by a genotype 4 strain of human hepatitis E virus.
Hepatitis E virus (HEV) is an important pathogen. The animal strain of HEV, swine HEV, is related to human HEV. The genotype 3 swine HEV can infect humans and genotype 3 human HEV can infect pigs. The genotype 4 swine and human HEV strains are genetically related, but it is unknown whether genotype 4 human HEV can infect pigs. A swine bioassay was utilized in this study to determine whether genotype 4 human HEV can infect pigs. Fifteen, 4-week-old, specific-pathogen-free pigs were divided into three groups of five each. Group 1 pigs were each inoculated intravenously with PBS buffer as negative controls, group 2 pigs similarly with genotype 3 human HEV (strain US-2), and group 3 pigs similarly with genotype 4 human HEV (strain TW6196E). Serum and fecal samples were collected at 0, 7, 14, 21, 28, 35, 42, 49, and 56 days postinoculation (dpi) and tested for evidence of HEV infection. All pigs were necropsied at 56 dpi. As expected, the negative control pigs remained negative. The positive control pigs inoculated with genotype 3 human HEV all became infected as evidenced by detection of HEV antibodies, viremia and fecal virus shedding. All five pigs in group 3 inoculated with genotype 4 human HEV also became infected: fecal virus shedding and viremia were detected variably from 7 to 56 dpi, and seroconversion occurred by 28 dpi. The data indicated that genotype 4 human HEV has an expanded host range, and the results have important implications for understanding the natural history and zoonosis of HEV.


Eperisone, an antispastic agent, possesses vasodilating actions on the guinea-pig basilar artery.
The effects of eperisone, an antispasmodic, on the electrical and mechanical properties of smooth muscle cells of the guinea-pig basilar artery were investigated. Eperisone (below 50 microM) did not modify the membrane potential, membrane resistance, excitatory junction potential evoked by perivascular nerve stimulation or the K- and 5-hydroxytryptamine-induced depolarizations. However, in concentrations over 10 microM, this agent reversibly blocked the spontaneously generated and evoked action potentials in the presence of 5 to 8 mM tetraethylammonium. The contractions evoked by high concentrations of K, 5-hydroxytryptamine or direct muscle stimulation in the presence of tetraethylammonium were dose dependently inhibited by eperisone, in concentrations over 1 microM. In Ca-free 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid-containing solution, 5-hydroxytryptamine produced only a single contraction. Eperisone inhibited this contraction to the same extent as that observed in the presence of Ca. These results indicate that eperisone possesses the property of a Ca antagonist on smooth muscle tissues of the guinea-pig basilar artery, in addition to the action of antispastic agent, i.e., this agent blocks the voltage-dependent influx of Ca at the smooth muscle membrane, but not at the nerve terminals, and inhibits the action of Ca in cells through inhibition of the contractile protein.


Vacuumlike Jet Fragmentation in a Dense QCD Medium.
We study the fragmentation of a jet propagating in a dense quark-gluon plasma. Using a leading, double-logarithmic approximation in perturbative QCD, we compute for the first time the effects of the medium on multiple vacuumlike emissions. We show that, due to the scatterings off the plasma, the in-medium parton showers differ from the vacuum ones in two crucial aspects: their phase-space is reduced and the first emission outside the medium can violate angular ordering. We compute the jet fragmentation function and find results in qualitative agreement with LHC measurements.


Amplification of epidermal growth factor receptor gene but no evidence of ras mutations in primary human esophageal cancers.
Primary esophageal squamous cell carcinomas from 41 patients were analyzed for the presence of proto-oncogene alterations associated with this malignancy. The occurrence of activating ras gene mutations in 25 tumors was determined using oligomer hybridization of target sequences amplified by polymerase chain reaction. We found no evidence for mutations in codons 12 and 61 of the H-ras, K-ras, and N-ras genes, nor in codon 13 of the K-ras and N-ras loci in any of these tumors. The apparent absence of activated ras oncogene in esophageal cancers represents a possible exception to the presence of these mutations found consistently in numerous other types of human malignancies, and is in striking contrast to the 40% prevalence of ras mutations in human colorectal cancers. Southern blot hybridization experiments with DNAs from tumors demonstrated amplification of the epidermal growth factor receptor gene (c-erbB) in two of 25 carcinomas. No amplification of the structurally related c-erbB2 (neu) gene was detected. In three out of 12 carcinomas, the level of epidermal growth factor receptor RNA was significantly higher than in normal esophageal mucosal tissue. Our results suggest that enhanced transcription of the epidermal growth factor receptor gene is associated with the development of some esophageal cancers.


Disease-Modifying Drug Uptake and Health Service Use in the Ageing MS Population.
Evidence regarding the efficacy or effectiveness of the disease-modifying drugs (DMDs) in the older multiple sclerosis (MS) population is scarce. This has contributed to a lack of evidence-based treatment recommendations for the ageing MS population in practice guidelines. We examined the relationship between age (<55 and ≥55 years), DMD exposure and health service use in the MS population. We conducted a population-based observational study using linked administrative health data from British Columbia, Canada. We selected all persons with MS and followed from the most recent of their first MS or demyelinating event, 18th birthday or 01-January-1996 (index date) until the earliest of emigration, death or 31-December-2017 (study end). We assessed DMD exposure status over time, initially as any versus no DMD, then by generation (first or second) and finally by each individual DMD. Age-specific analyses were conducted with all-cause hospitalizations and number of physician visits assessed using proportional means model and negative binomial regression with generalized estimating equations. We included 19,360 persons with MS (72% were women); 10,741/19,360 (56%) had ever reached their 55th birthday. Person-years of follow-up whilst aged <55 was 132,283, and 93,594 whilst aged ≥55. Any DMD, versus no DMD in the <55-year-olds was associated with a 23% lower hazard of hospitalization (adjusted hazard ratio, aHR0.77; 95%CI 0.72-0.82), but not in the ≥55-year-olds (aHR0.95; 95%CI 0.87-1.04). Similar patterns were observed for the first and second generation DMDs. Exposure to any (versus no) DMD was not associated with rates of physician visits in either age group (<55 years: adjusted rate ratio, aRR1.02; 95%CI 1.00-1.04 and ≥55 years: aRR1.00; 95%CI 0.96-1.03), but variation in aRR was observed across the individual DMDs. Our study showed beneficial effects of the DMDs used to treat MS on hospitalizations for those aged <55 at the time of exposure. In contrast, for individuals ≥55 years of age exposed to a DMD, the hazard of hospitalization was not significantly lowered. Our study contributes to the broader understanding of the potential benefits and risks of DMD use in the ageing MS population.


Effect of mild hypothermia on uncontrollable intracranial hypertension after severe head injury.
Recent experimental studies have demonstrated that mild hypothermia at about 34 degrees C can be effective in the control of intracranial hypertension. A randomized controlled study of mild hypothermia was carried out in 33 severely head-injured patients. All patients fulfilled the following criteria: 1) persistent intracranial pressure (ICP) greater than 20 mm Hg despite fluid restriction, hyperventilation, and high-dose barbiturate therapy; 2) an ICP lower than the mean arterial blood pressure; and 3) a Glasgow Coma Scale score of 8 or less. The patients were divided into two groups: one received mild hypothermia (16 patients) and one served as a control group (17 patients). Mild hypothermia significantly reduced the ICP and increased the cerebral perfusion pressure. Eight patients (50%) in the hypothermia group and three (18%) in the control group survived (p < 0.05), while five (31%) in the hypothermia group and 12 (71%) in the control group died of uncontrollable intracranial hypertension (p < 0.05). In five patients in the hypothermia group, cerebral blood flow was measured by the hydrogen clearance method and arteriojugular venous oxygen difference was evaluated before and during mild hypothermia. Mild hypothermia significantly decreased the cerebral blood flow, arteriojugular venous oxygen difference, and cerebral metabolic rate of oxygen (p < 0.01). The results of this preliminary investigation suggest that mild hypothermia is a safe and effective method to control traumatic intracranial hypertension and to improve mortality and morbidity rates.


Growth of Mediastinal Bronchial Artery Aneurysms in a Patient With Bronchiectasis.
Mediastinal bronchial artery aneurysm (BAA) is a rare and life-threatening disease. We experienced the first case confirming that, despite only slight deterioration of bronchiectasis, mediastinal BAAs expanded remarkably. A 61-year-old female was hospitalized because of hemoptysis. Her respiratory condition required intubated mechanical ventilation. Bronchial artery angiography unexpectedly found unruptured mediastinal BAAs. These BAAs were enlarged compared with those seen in a computed tomography (CT) taken 5 years before. We successfully embolized both BAAs and peripheral arteries. Mediastinal BAAs are capable of increasing more rapidly than a slightly deteriorated underlying bronchiectasis. For rapid and accurate diagnosis of BAA, bronchial artery angiography is important.


αβ-Dehydrocurvularin isolated from the fungus Aspergillus welwitschiae effectively inhibited the behaviour and development of the root-knot nematode Meloidogyne graminicola in rice roots.
The root-knot nematode Meloidogyne graminicola has become a serious threat to rice production as a result of the cultivation changes from transplanting to direct seeding. The nematicidal activity of Aspergillus welwitschiae have been investigated in vitro, and the disease control efficacy of the active compound has been evaluated under greenhouse and field conditions. The active compound αβ-dehydrocurvularin (αβ-DC), isolated by nematicidal assay-directed fractionation, showed significant nematicidal activity against M. graminicola, with a median lethal concentration (LC50) value of 122.2 μg mL- 1. αβ-DC effectively decreased the attraction of rice roots to nematodes and the infection of nematodes and also suppressed the development of nematodes under greenhouse conditions. Moreover, αβ-DC efficiently reduced the root gall index under field conditions. To our knowledge, this is the first report to describe the nematicidal activity of αβ-DC against M. graminicola. The results obtained under greenhouse and field conditions provide a basis for developing commercial formulations from αβ-DC to control M. graminicola in the future.


The bacterial aetiology of adult community-acquired pneumonia in Asia: a systematic review.
Community-acquired pneumonia (CAP) is a major cause of adult mortality in Asia. Appropriate empirical treatment depends on knowledge of the pathogens commonly responsible. However, assessing the aetiological significance of identified organisms is often difficult, particularly with sputum isolates that might represent contamination with oropharyngeal flora. A systematic review of all adult CAP aetiology studies from Asia, excluding the Middle East, published in English between 1 January 1990 and 1 March 2012 was conducted. Forty-eight studies reporting on 10 423 patients were included, representing data from China, India, Indonesia, Japan, Malaysia, The Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam. Data from large parts of Asia were unavailable and there was substantial heterogeneity in methodology. As in western studies, Streptococcus pneumoniae, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella spp. and Haemophilus influenzae were all significant pathogens. However, compared with western studies, S. pneumoniae was of less relative importance. Gram-negative bacilli and Mycobacterium tuberculosis were more important, and in northeast Thailand Burkholderia pseudomallei was a major pathogen. These data have major implications for diagnostic strategies and empirical treatment. Narrow-spectrum antibiotics targeting S. pneumoniae may be inappropriate in many Asian settings, and agents active against TB may lead to partial response and delayed TB diagnosis.


Seeds of Success: Empowering Latina STEM Girl Ambassadors Through Role Models, Leadership, and STEM-Related Experiences.
Gender stereotypes and lack of access to relatable role models, mentors, and STEM opportunities have been suggested to deter middle school girls and students from underrepresented backgrounds away from STEM. Seeds of Success, an out-of-school program, is designed to inspire girls to consider STEM careers by countering gender stereotypes through relatable role models, promoting STEM confidence through STEM workshops and hands-on activities, and encouraging alignment between cultural and STEM identities through community-based STEM projects that develop leadership skills. Since 2015, the program has impacted 453 students who in turn have reached more than 42,777 people in Puerto Rico through their STEM Ambassadors projects. A robust mix-method evaluation of the 2020 and 2021 cohorts demonstrates significant improvements in participants' STEM attitudes and science identity, as well as in their self-perception as a leader, confidence in their ability to succeed in science, knowledge about STEM careers and opportunities, and access to STEM role models. Moreover, 95% of participants intend to continue participating in STEM activities after the program and overall scores for the entire survey were significantly higher after the program than before. We discuss lessons learned for other programs seeking to empower girls from historically underserved backgrounds in STEM.


Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.
SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.


Chronic adaptations in proximal tubular H/HCO3 transporters.
Chronic acidosis, chronic K deficiency, and chronic hyperfiltration all lead to similar parallel increases in Na/H antiporter and Na/3HCO3 cotransporter activities. These effects persist when the transporters are removed from the inducing environment, and thus represent memory effects. The effect of acidosis on the Na/H antiporter can be reproduced by preincubating cultured proximal tubule cells chronically in acid media, suggesting that low extracellular fluid pH is an important signal in acidosis. The specific extracellular signals in chronic K deficiency and chronic hyperfiltration have not been elucidated. The effect of acid preincubation on Na/H antiporter activity in cultured proximal tubule cells is dependent on protein synthesis and is associated with increased abundance of mRNA for the Na/H antiporter. The cell signalling pathways which mediate these effects have not been determined. However, the common response in chronic acidosis, chronic K deficiency, and chronic hyperfiltration to the demand for increased H transport, suggests that a common signalling pathway will be found in all these conditions.


[Electron-acceptor (acid) properties of the contents of blood platelet intracellular granules and their significance for the reactions of these cells].
The fluorescent marker method and measurements of aggregation were utilized to study the significance of the acidic intragranular space in blood platelets. Acridine orange is liberated from 5-HT granules after alkalinization by the ammonia ion which inhibits the induction of platelet aggregation by ADP and causes the platelet disaggregation. At low doses, ammonia ion enhances ADP-induced aggregation. The transformation kinetics of 5-HT granules was investigated in the course of clot formation with a new instrument that simultaneously monitors the light transmittance (aggregation, clot formation) and fluorescence intensity (accumulation and liberation of fluorescent marker). These experiments provide the evidence that processes of fibrin filament sedimentation and fibrin-blood platelet interaction were followed by a liberation of fluorescent marker from 5-HT granules.


Duality of alpha-subunit of canine kidney sodium- and potassium-activated adenosinetriphophatase in electrophoresis.
Sodium- and potassium-activated adenosinetriphosphatase (Na+, K+-ATPase) purified from dog kidney outer medulla was examined by polyacrylamide gel electrophoresis and by photoaffinity labeling with N-(ouabain)-N'-(2-nitro-4-azidophenyl)-ethylenediamine (NAP-ouabain). The large subunit band (alpha-band) split into two bands on the gel after the enzyme was heat-treated in the presence of 1% sodium dodecylsulfate (SDS). Of the two bands (alpha I and alpha II), alpha I had the same electrophoretic mobility as the original band, while alpha II moved slightly faster. Total conversion into alpha II was not observed, about half of the original remaining as alpha I. Below 60 degree C, heat treatment did not produce alpha II. Phenylmethylsulfonyl fluoride did not prevent the appearance of alpha II. Both alpha I and alpha II were labeled with [3H]NAP-ouabain. Nonspecific incorporation of [3H]NAP-ouabain also occurred irrespective of illumination, but it was removed either by diffusion during staining and destaining of the gel or by treatment of the enzyme with trichloroacetic acid. It is tentatively concluded that the splitting of the band reflects some intrinsic differences in situ of the alpha-subunit of dog kidney membrane Na+,K+-ATPase.


Circulating brain-derived neurotrophic factor and indices of metabolic and cardiovascular health: data from the Baltimore Longitudinal Study of Aging.
Besides its well-established role in nerve cell survival and adaptive plasticity, brain-derived neurotrophic factor (BDNF) is also involved in energy homeostasis and cardiovascular regulation. Although BDNF is present in the systemic circulation, it is unknown whether plasma BDNF correlates with circulating markers of dysregulated metabolism and an adverse cardiovascular profile. To determine whether circulating BDNF correlates with indices of metabolic and cardiovascular health, we measured plasma BDNF levels in 496 middle-age and elderly subjects (mean age approximately 70), in the Baltimore Longitudinal Study of Aging. Linear regression analysis revealed that plasma BDNF is associated with risk factors for cardiovascular disease and metabolic syndrome, regardless of age. In females, BDNF was positively correlated with BMI, fat mass, diastolic blood pressure, total cholesterol, and LDL-cholesterol, and inversely correlated with folate. In males, BDNF was positively correlated with diastolic blood pressure, triglycerides, free thiiodo-thyronine (FT3), and bioavailable testosterone, and inversely correlated with sex-hormone binding globulin, and adiponectin. Plasma BDNF significantly correlates with multiple risk factors for metabolic syndrome and cardiovascular dysfunction. Whether BDNF contributes to the pathogenesis of these disorders or functions in adaptive responses to cellular stress (as occurs in the brain) remains to be determined.


Psychosocial Factors Associated with Paternal Perinatal Depression in the United States: A Systematic Review.
Paternal perinatal depression can occur in approximately one out of ten fathers. However, research within this population is limited. A previous systematic review suggested that United States had higher rates of paternal perinatal depression compared to other countries. Therefore, this systematic review identified psychosocial factors for depression during the perinatal period in fathers who live in the United States. A literature search was conducted from multiple databases using keywords and MeSH terms to retrieve articles up to the year 2019. Twenty five articles were included in this review. A social-ecological framework was applied to identify psychosocial factors associated with paternal depression. Individual factors include prior history of depression, having maladaptive cognitive coping styles, fathers who self-identified as African-American or Hispanic, parenting stress, substance use, and history of criminal conviction. Interpersonal factors include lack of social support, quality of relationship with the mother of the baby, coparenting conflict, quality of current and childhood relationships with their own parents, and maternal depression. Community factors include frequent daily experiences with racism, and limited access to transportation and housing. These findings underscore the importance of assessing depression and developing father-inclusive interventions that address the psychological needs of fathers.


Leadership in neurosurgery.
These are challenging times for neurosurgery. Although no one can predict our future, great changes are in the wind--many of which we are powerless to prevent. We must all take on added social responsibility, above and beyond that of patient care. The leadership of your organization can only act with the support of active and concerned neurosurgeons who are willing to participate in many programs available to our profession. The individual must personally embrace the leadership standards of Sir William Osler and Harvey Cushing. One of the privileges of giving a presidential address is to pay public homage to those who have been supportive and instrumental in my long professional journey. During my residency, Dr. Dwight Parkinson was my mentor and teacher and set a wonderful standard for the ideal practice of neurosurgery. Decisions were black or white, never gray, with Dr. Parkinson, who left little doubt as to the correct way to handle clinical problems. He was, and continues to be, one of the most incisive, imaginative, innovative scientific minds in neurosurgery, and I owe him a great debt of gratitude. Two other men influenced my neurosurgical development. They are Dr. William Horsey, formerly neurosurgeon at the St. Michael's Hospital in Toronto, and Dr. Peardon Donaghy, with whom I spent a most enjoyable and productive year in Burlington at his microvascular neurosurgical laboratory. These two men demonstrated the humility, warmth, and kindness to patients that cannot be learned by formal study, but comes from observing the example of people who manifest those qualities in their own personality.(ABSTRACT TRUNCATED AT 250 WORDS)


A multidisciplinary evaluation of the child with a visually related learning disability.
It is conceded that not all learning disabilities result from vision or visual perceptual problems. Optometrists are advised to familiarize themselves with techniques employed by other disciplines dealing with learning disabled children. It is suggested that they direct themselves to the myriad of variables involved in the care of the under achieving or non-achieving child so that their own specific techniques will become of greater value to the patient.


Recent progress in dietary fiber (plantix) in human nutrition.
Dietary fiber was extensively discussed in an article by G.A. Spiller and R.J. Amen in this journal in 1975 (Volume 7 Issue 1). The progress in this field has been tremendous in the past 2 years. What was an uncertain field in 1975 and what at that time to some investigators still appeared as a hypothesis or fad without much proof has turned into a much more respected part of nutritional sciences. The scientific quality of recent studies on dietary fiber in human nutrition shows a great deal of sophistication and care. Improved analytical methodologies are being used more extensively. Many nutritionists and clinicians have accepted the fact that a reasonable increase in the dietary fiber intake in the U.S. and U.K would be advisable. In this article, the possible beneficial effects of dietary fiber on health, the possible harmful side effects, and the food science aspects are carefully discussed after an update on chemistry, analytical procedures, and nomenclature. Undoubtedly, dietary fiber has found a new niche in the sciences of nutrition, medicine, epidemiology, and foods.


Myocardial infarction in young patients without coronary atherosclerosis: assume primary antiphospholipid syndrome until proved otherwise.
The objective of this study was to highlight the need for investigation of antiphospholipid (aPL) antibodies in patients presenting with myocardial infarction (MI) and normal coronary arteries at angiography. We present five patients who were found to have had an MI without evidence of atherosclerosis. All had aPL antibodies and thus fulfilled the diagnosis of antiphospholipid syndrome (APS). Who did not have recurrent events on long-term anticoagulation maintaining an international normalised ratio of 3-4. This study suggests that APS is probably a major cause of MI in those with normal coronary arteries at angiography. It is an important diagnosis to make as they do not require anti-atherosclerotic treatment but appear, from this case series, to do well on high-dose warfarin. Further clinical studies are necessary to look at prevalence and best management in these patients.


A new staging system for cardiac transthyretin amyloidosis.
Cardiac transthyretin (ATTR) amyloidosis is an increasingly recognized, progressive, and fatal cardiomyopathy, the natural history of which remains unclear. We sought to establish and validate a new prognostic staging system applicable to patients with both wild-type ATTR (ATTRwt) and hereditary variant ATTR (ATTRv) amyloid cardiomyopathy. Eight hundred and sixty-nine patients with cardiac ATTR amyloidosis (553 with ATTRwt and 316 with ATTRv) attending the UK National Amyloidosis Centre were stratified into three disease stages at baseline on the basis of cut points in two universally measured biomarkers, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR). Stage I was defined as NT-proBNP ≤3000 ng/L and eGFR ≥45 ml/min, Stage III was defined as NT-proBNP >3000 ng/L and eGFR <45 ml/min, and the remainder were Stage II. The staging system was validated in a cohort of 318 patients with cardiac ATTR amyloidosis from France. Median survival among 393 (45%) Stage I patients was 69.2 months, 334 (38%) Stage II patients was 46.7 months, and 142 (16%) Stage III patients was 24.1 months (P < 0.0001). After adjusting for age, compared with Stage I, the hazard ratio (HR) for death for Stage II was 2.05 [confidence interval (CI) 1.54-2.72, P < 0.001] and for Stage III was 3.80 (CI 2.73-5.28, P < 0.001). HRs and statistical significance were little altered by transthyretin genotype and were maintained in the validation cohort. This simple, universally applicable staging system stratifies patients with both ATTRwt and ATTRv amyloid cardiomyopathy into prognostic categories. It will be of value in the design of forthcoming clinical trials of novel amyloid-specific therapies.


Parameters Associated with Adverse Fetal Outcomes in Parvovirus B19 Congenital Infection.
Objective To investigate the clinical and sonographic parameters associated with adverse fetal outcomes in patients with congenital parvovirus B19 infection managed by intrauterine transfusion. Methods This was a single-center retrospective study conducted from January 2005 to December 2016 that assessed patients with singleton pregnancies with fetal parvovirus infection confirmed by a polymerase chain reaction of the amniotic fluid or fetal blood samples who underwent at least one intrauterine transfusion. The maternal characteristics, sonographic findings and parameters related to intrauterine transfusion were compared between the two groups (recovery/non-recovery), who were categorized based on fetal response after in-utero transfusions. Progression to fetal death or delivery without fetal recovery after the transfusions was considered non-recovery and categorized as an adverse outcome. Results The final analysis included ten singleton pregnancies: seven of which were categorized into the recovery group and three of which into the non-recovery group. The baseline characteristics were similar between the groups. All fetuses were hydropic at the time of diagnosis. No significant differences related to sonographic or intrauterine transfusion parameters were identified between the groups; however, the non-recovery group tended to have an increased number of sonographic markers and lower fetal hemoglobin and platelet levels before the transfusion. Conclusion We were unable to firmly establish the clinical or sonographic parameters associated with adverse fetal outcomes in patients with parvovirus infection managed with intrauterine transfusions; however, edema, placental thickening and oligohydramnios may indicate greater fetal compromise and, subsequently, adverse outcomes. However, further studies are necessary, mainly due to the small number of cases analyzed in the present study.


[The nurse opposite emotions].
When one approaches a work of classical literature best thing can do is shut up and let that speak for itself "La señorita Cora" doubly deserves the title of classic. First, because it still extraordinary tales of Cortázar, some like this reach the condition of anthological parts. Secondly, because within the literature starring nurses, it is difficult to find a work that explore the emotional world of nursing care with such lucidity. Therefore, much more interesting that read this comment is read and reread the story. And I say back to read because the classical works are characterized by the more return on them, far from tired, offer us new perspectives which we had not seen until then.


A threshold photoelectron-photoion coincidence spectrometer with double velocity imaging using synchrotron radiation.
A novel threshold photoelectron-photoion coincidence (TPEPICO) imaging spectrometer at the U14-A beamline of the Hefei National Synchrotron Radiation Laboratory is presented. A set of open electron and ion lenses are utilized to map velocity imaging of photoelectrons and photoions simultaneously, in which a repelling electric field using an extra lens is applied to magnify images of photoelectrons instead of traditional accelerating electric field in order to suppress the contribution of energetic electrons in the threshold photoelectron spectroscopy (TPES) and the mass-selected TPEPICO spectroscopy. The typical energy resolution of TPES is measured to be 9 meV (full width at half maximum), as shown on the (2)P(1/2) ionization of argon. The measured mass resolving power for the present TPEPICO imaging spectrometer is above 900 of M/DeltaM. Subsequently as a benchmark, oxygen molecule is photoionized by monochromatic synchrotron radiation at 20.298 eV and dissociates to an oxygen atomic ion and a neutral oxygen atom, and the translation energy distribution of oxygen atomic ion is measured by the time-sliced imaging based on mass-selected TPEPICO experiment. The kinetic energy resolution of the present ion velocity imaging is better than 3% of DeltaE/E.


Complex transmission dynamics of clonally related virulent Mycobacterium tuberculosis associated with barhopping by predominantly human immunodeficiency virus-positive gay men.
Limited data suggest that measures to reduce tuberculosis transmission should be based on locations rather than on personal contacts. Molecular epidemiologic methods (analysis of IS6110 patterns, spoligotypes, variable numbers of tandem DNA repeats, and automated DNA sequence data) identified a cohort of 48 persons who were infected with progeny of the same Mycobacterium tuberculosis strain. Epidemiologic investigation documented that a large proportion of the patients were gay white human immunodeficiency virus-positive men. Most practiced barhopping, an activity that involved patronizing many bars in the same neighborhood each night. Few subjects were directly linked to more than 1 or 2 other persons by conventional investigation methods, which shows that the transmission dynamics were unusually complex compared with most previously described episodes of strain spread. The data support the concept that identification of locations where pathogen dissemination likely occurs may provide additional strategies for targeted tuberculosis control.


Adaptive language model training for molecular design.
The vast size of chemical space necessitates computational approaches to automate and accelerate the design of molecular sequences to guide experimental efforts for drug discovery. Genetic algorithms provide a useful framework to incrementally generate molecules by applying mutations to known chemical structures. Recently, masked language models have been applied to automate the mutation process by leveraging large compound libraries to learn commonly occurring chemical sequences (i.e., using tokenization) and predict rearrangements (i.e., using mask prediction). Here, we consider how language models can be adapted to improve molecule generation for different optimization tasks. We use two different generation strategies for comparison, fixed and adaptive. The fixed strategy uses a pre-trained model to generate mutations; the adaptive strategy trains the language model on each new generation of molecules selected for target properties during optimization. Our results show that the adaptive strategy allows the language model to more closely fit the distribution of molecules in the population. Therefore, for enhanced fitness optimization, we suggest the use of the fixed strategy during an initial phase followed by the use of the adaptive strategy. We demonstrate the impact of adaptive training by searching for molecules that optimize both heuristic metrics, drug-likeness and synthesizability, as well as predicted protein binding affinity from a surrogate model. Our results show that the adaptive strategy provides a significant improvement in fitness optimization compared to the fixed pre-trained model, empowering the application of language models to molecular design tasks.


Evaluation of Kappa Index as a Tool in the Diagnosis of Multiple Sclerosis: Implementation in Routine Screening Procedure.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Previous studies have shown that cerebrospinal fluid (CSF) kappa free light chains (K-FLCs) may have a role in MS diagnosis. In this regard, the kappa index (K-Index) has demonstrated higher sensitivity, and slightly lower specificity than oligoclonal bands (OCBs), the gold standard for the detection of intrathecal immunoglobulin synthesis, a feature of MS. Here, we evaluated the performance of the K-Index (K-Index = CSF/serum K-FLC divided by CSF/serum albumin) for the differential diagnosis of MS in a cohort of patients with suspected MS. K-FLCs were quantitatively measured in parallel serum and CSF samples by turbidimetry (Freelite Mx reagent on an Optilite system, The Binding Site Group Ltd). From 160 (63.4%) of a total of 252 patients who had K-FLC in CSF <0.03 mg/dl, below the sensitivity limit of the technique, only one had a diagnosis of MS. However, the absence of OCB in this same patient suggested no synthesis of intrathecal immunoglobulin. Globally, MS patients presented significantly higher K-Index levels than patients without an MS diagnosis (66.96 vs. 0.025, respectively; p < 0.0001). In agreement, patients with positive OCB testing also exhibited higher K-Index levels than patients negative for OCB (65.02 vs. 0.024, respectively; p < 0.0001). An optimal K-Index cutoff of 3.045 was defined by receiver operating characteristic (ROC) analysis for screening suspected MS, achieving a higher diagnostic sensitivity and slightly lower specificity than OCB (Sens. 0.9778 and Spec. 0.8629 vs. Sens. 0.8889 and Spec. 0.9086, respectively). A previously reported K-Index cutoff of 6.6 also showed good diagnostic performance (Sens. 0.9333; Spec. 0.8731), validating its power as a diagnostic biomarker for MS. Finally, a time- and cost-effective algorithm for MS screening is proposed that would offer an initial rapid evaluation of the intrathecal immunoglobulin synthesis through the K-FLC in CSF and K-Index analysis, followed by reflexing OCB testing that may be ordered more selectively.


Treatment Persistence Between Long-Acting Injectable Versus Orally Administered Aripiprazole Among Patients with Schizophrenia in a Real-World Clinical Setting in Japan.
Persistence with antipsychotic treatment is critical in managing patients with schizophrenia. To evaluate whether aripiprazole long-acting injection (aripiprazole once-monthly, AOM) can contribute to longer treatment persistence compared with daily orally administered aripiprazole (OA) in real-world clinical settings in Japan, treatment persistence in patients with schizophrenia was compared between patients treated with AOM and those with OA, using a claims database compiled by JMDC Inc., Tokyo, Japan. Data of patients with schizophrenia who newly initiated AOM or OA treatment between May 2015 and November 2017 were analyzed. The Cox proportional hazard model was used to estimate the hazard ratio (HR) for treatment discontinuation of AOM vs. OA treatment, adjusted for age, sex, chlorpromazine-equivalent dose of antipsychotics, and the number of psychiatric hospitalizations. The analysis included 198 patients in the AOM group and 1240 patients in the OA group (mean age 38.4 ± 11.9 years and 39.3 ± 12.4 years, respectively). The AOM group was significantly less likely to discontinue treatment than the OA group (adjusted HR 0.54, 95% confidence interval [CI] 0.43-0.68). When using the tolerable patients extracted from the OA group (i.e., patients with at least two OA prescriptions; n = 983) vs. the whole AOM group, AOM users were again significantly less likely to discontinue treatment (adjusted HR 0.67, 95% CI 0.53-0.86). AOM was associated with longer treatment persistence than OA in the antipsychotic treatment of patients with schizophrenia in real-world clinical settings in Japan, suggesting that the use of AOM may contribute to longer antipsychotic treatment.


Understanding and controlling the efficiency of Au24M(SR)18 nanoclusters as singlet-oxygen photosensitizers.
Singlet oxygen, 1O2, can be generated by molecules that upon photoexcitation enable the 3O2 → 1O2 transition. We used a series of atomically precise Au24M(SR)18 clusters, with different R groups and doping metal atoms M. Upon nanosecond photoexcitation of the cluster, 1O2 was efficiently generated. Detection was carried out by time-resolved electron paramagnetic resonance (TREPR) spectroscopy. The resulting TREPR transient yielded the 1O2 lifetime as a function of the nature of the cluster. We found that: these clusters indeed generate 1O2 by forming a triplet state; a more positive oxidation potential of the molecular cluster corresponds to a longer 1O2 lifetime; proper design of the cluster yields results analogous to those of a well-known reference photosensitizer, although more effectively. Comprehensive kinetic analysis provided important insights into the mechanism and driving-force dependence of the quenching of 1O2 by gold nanoclusters. Understanding on a molecular basis why these molecules may perform so well in 1O2 photosensitization is instrumental to controlling their performance.


Isolation and selection of a bacteriophage-typing set for Enterobacter cloacae.
Seventy-six phages active against Enterobacter cloacae were isolated from sewage and other sources. They were tested at RTD on 92 selected strains of E. cloacae and their lytic reactions were used to select phages for a typing set. Numerical analysis by the Jaccard coefficient was used to assess the similarity between the phages. A computer-based test selection procedure selected sub-sets of phages to discriminate between all 92 E. cloacae strains and within the most frequent serological groups. A subjective analysis of the candidate phages based on similarity, clarity of plaque and frequency of lysis was combined with the computer selected sub-sets to produce a final set of 25 phages that gave a good theoretical discrimination of clinical isolates of E. cloacae.


[Doppler sonographic flow parameter of the anterior cerebral artery in patent ductus arteriosus of the newborn infant compared to a healthy control sample].
33 premature infants (age: 32 +/- 3 weeks; birth weight 1,268 +/- 535 gs) with the clinical signs of patent ductus arteriosus Botalli (PDA) and a control group of 96 healthy infants (age: 37 +/- 4 weeks; birth weight 2 348 +/- 944 gs) were investigated. Pulsed doppler recordings were obtained in the anterior cerebral arteries (ACA) and compared with the flow pattern in the truncus coeliacus (TC). In all children the maximal systolic velocity (Vs), the endsystolic (Ves) and the enddiastolic velocity (Ved) and the pulsatility-index (PI) were measured. The 96 healthy premature born infants showed the following velocities: Vs: 41 +/- 12 cm X sec-1; Ves: 19 +/- 7 cm X sec-1; Ved: 10 +/- 4 cm X sec-1. The pulsatility-index was 0.74 +/- 0.08. In children with PDA all velocities were significantly lower than in the healthy control group: Vs: 31 +/- 10 cm X sec-1; Ves: 7 +/- 6 cm X sec-1; Ved: -1 +/- 5 cm X sec-1. Ved was more decreased than Vs resulting in a significant increase in PI (1.04 +/- 0.14). 22 infants with surgically proven large PDA (age: 31 +/- 3 weeks; birth weight: 1,160 +/- 467 gs) showed significant lower velocities (Vs: 34 +/- 8 cm X sec-1; Ves: 4 +/- 4 cm X sec-1; Ved: -4 +/- 4 cm X sec-1) in comparison with the healthy control group and the 11 children with small PDA (age: 33 +/- 4 weeks; birth weight: 1,494 +/- 621 gs).(ABSTRACT TRUNCATED AT 250 WORDS)


Quadriceps strength in women with a previous hip fracture: relationships to physical ability and bone mass.
Associations between physical ability, level of current physical activity and bone mass were examined in 47 elderly women (mean age 80 years) who had suffered from a hip fracture 3-36 months (mean 17 months) previously. Measures of physical ability included isokinetic quadriceps strength of both the non-fractured and fractured leg, and walking and stair climbing speed. An estimate of current physical activity was made using the Northwick Park activity index questionnaire specifically designed for hip fracture patients. Bone mineral density of the spine and hip (Ward's triangle, femoral neck and trochanter) was assessed by dual energy X-ray absorptiometry. Relationships between the measured parameters were analysed using multiple regression analyses, taking into account the confounding effects of age, height, weight and months since fracture. Quadriceps strength of the fractured leg was on average 18% lower than that of the contralateral leg (p < 0.001). Quadriceps strength of the fractured leg proved to be the most robust predictor of walking speed (Rpartial = 0.69, p < 0.0001), stair climbing speed (Rpartial = 0.46, p < 0.001) and the activity index (Rpartial = 0.56, p < 0.0001). Bone mineral density was independently predicted only by body weight (Rpartial range: 0.45-0.72, p < 0.001), not by any of the parameters of physical ability or by the Northwick Park activity index. In conclusion, quadriceps strength is markedly affected in women with a previous hip fracture and is associated with walking ability and level of physical activity. This study showed that bone mass is linked to body weight, not to physical ability and activity. Thus, the main benefit of muscle strengthening exercises in these women may be to promote mobility.


The Effects of 16 Weeks of Exercise Training on Neutrophil Functions in Breast Cancer Survivors.
Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 - 60 minute mixed mode aerobic exercises, comprising 10 - 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 109/L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease. ClinicalTrials.gov, identifier NCT03760536.


Effects of different dietary fats on mammary carcinogenesis.
Mammary tumor induction was examined in female Fischer rats fed a low-corn oil, a high-corn oil, a high-lard, a high-beef tallow, or a high-coconut oil diet since weaning. The diets were prepared by adding the experimental fat to a basal diet containing sufficient essential fatty acids for growth. These diets differed only in the concentration or type of dietary fat. The rats were given a single i.v. dose (50 mg/kg body weight) of N-nitrosomethylurea at 50 days of age. Mammary tumor incidences 28 weeks after N-nitrosomethylurea treatment in rats on low-corn oil, high-corn oil, high-lard, high-beef tallow, and high-coconut oil diets were 33, 85, 65, 50, and 43%, respectively. The data show that an increase in fat intake enhances mammary carcinogenesis, but the magnitude of the increase depends on the type of fat. Further analyses showed that the total oleic and linoleic acid intake in the five groups of rats correlated positively (r = 0.95) with mammary tumor incidence, whereas the composition of the mammary tissue neutral lipids and phospholipids did not. Our data suggest that the total oleate and linoleate intake in the high-fat diet is the major factor influencing the incidence of tumors by N-nitrosomethylurea.


Microfluidics-assisted engineering of polymeric microcapsules with high encapsulation efficiency for protein drug delivery.
In this study, microfluidic technology was employed to develop protein formulations. The microcapsules were produced with a biphasic flow to create water-oil-water (W/O/W) double emulsion droplets with ultrathin shells. Optimized microcapsule formulations containing 1% (w/w) bovine serum albumin (BSA) in the inner phase were prepared with poly(vinyl alcohol), polycaprolactone and polyethylene glycol. All the particles were found to be intact and with a particle size of 23-47 μm. Furthermore, the particles were monodisperse, non-porous and stable up to 4 weeks. The encapsulation efficiency of BSA in the microcapsules was 84%. The microcapsules released 30% of their content within 168 h. This study demonstrates that microfluidics is a powerful technique for engineering formulations for therapeutic proteins.


An Enhanced Synthetic Multiclade DNA Prime Induces Improved Cross-Clade-Reactive Functional Antibodies when Combined with an Adjuvanted Protein Boost in Nonhuman Primates.
The search for an efficacious human immunodeficiency virus type 1 (HIV-1) vaccine remains a pressing need. The moderate success of the RV144 Thai clinical vaccine trial suggested that vaccine-induced HIV-1-specific antibodies can reduce the risk of HIV-1 infection. We have made several improvements to the DNA platform and have previously shown that improved DNA vaccines alone are capable of inducing both binding and neutralizing antibodies in small-animal models. In this study, we explored how an improved DNA prime and recombinant protein boost would impact HIV-specific vaccine immunogenicity in rhesus macaques (RhM). After DNA immunization with either a single HIV Env consensus sequence or multiple constructs expressing HIV subtype-specific Env consensus sequences, we detected both CD4(+) and CD8(+) T-cell responses to all vaccine immunogens. These T-cell responses were further increased after protein boosting to levels exceeding those of DNA-only or protein-only immunization. In addition, we observed antibodies that exhibited robust cross-clade binding and neutralizing and antibody-dependent cellular cytotoxicity (ADCC) activity after immunization with the DNA prime-protein boost regimen, with the multiple-Env formulation inducing a more robust and broader response than the single-Env formulation. The magnitude and functionality of these responses emphasize the strong priming effect improved DNA immunogens can induce, which are further expanded upon protein boost. These results support further study of an improved synthetic DNA prime together with a protein boost for enhancing anti-HIV immune responses. Even with effective antiretroviral drugs, HIV remains an enormous global health burden. Vaccine development has been problematic in part due to the high degree of diversity and poor immunogenicity of the HIV Env protein. Studies suggest that a relevant HIV vaccine will likely need to induce broad cellular and humoral responses from a simple vaccine regimen due to the resource-limited setting in which the HIV pandemic is most rampant. DNA vaccination lends itself well to increasing the amount of diversity included in a vaccine due to the ease of manufacturing multiple plasmids and formulating them as a single immunization. By increasing the number of Envs within a formulation, we were able to show an increased breadth of responses as well as improved functionality induced in a nonhuman primate model. This increased breadth could be built upon, leading to better coverage against circulating strains with broader vaccine-induced protection.


[Echographic and morphological parallels in the evaluation of the condition of the uterine scar].
Examinations of 86 women included echography, examination of the lower segment of the uterus during surgery, control manual examination of the postpartum uterus, and histologic examination of the tissues collected from the so-called cicatrix site. The authors claim that the criteria of the myometrial adequacy are the V-shaped lower segment of the uterus, at least 3-4 mm thick, continuous anterior contour of the uterus, the presence of a homogenous echostructure or a structure with small sites of elevated echogenicity. A balloon-shaped lower segment of the uterus and its thinness (less than 3 mm), no continuity in the uterine contour, predominance of elevated echogenicity incorporations in the echostructure of the cicatrix site indicate the inadequacy of the myometrium at the site of the transverse cicatrix in the lower segment of the uterus. The findings evidence that echography is a highly informative method for the diagnosis of the uterine cicatrix status and that echographic examinations should be widely used to choose the delivery mode for pregnant women with a history of abdominal delivery.


Temporal variation of the merozoite surface protein-2 gene of Plasmodium falciparum.
Extensive polymorphism of key parasite antigens is likely to hamper the effectiveness of subunit vaccines against Plasmodium falciparum infection. However, little is known about the extent of the antigenic repertoire of naturally circulating strains in different areas where malaria is endemic. To address this question, we conducted a study in which blood samples were collected from parasitemic individuals living within a small hamlet in Western Irian Jaya and subjected to PCR amplification using primers that would allow amplification of the gene encoding merozoite surface protein-2 (MSP2). We determined the nucleotide sequence of the amplified product and compared the deduced amino acid sequences to sequences obtained from samples collected in the same hamlet 29 months previously. MSP2 genes belonging to both major allelic families were observed at both time points. In the case of the FC27 MSP2 family, we observed that the majority of individuals were infected by parasites expressing the same form of MSP2. Infections with parasites expressing 3D7 MSP2 family alleles were more heterogeneous. No MSP2 alleles observed at the earlier time point were detectable at the later time point, either for the population as a whole or for individuals who were assayed at both time points. We examined a subset of the infected patients by using blood samples taken between the two major surveys. In no patients could we detect reinfection by a parasite expressing a previously encountered form of MSP2. Our results are consistent with the possibility that infection induces a form of strain-specific immune response against the MSP2 antigen that biases against reinfection by parasites bearing identical forms of MSP2.


Musculoskeletal Injuries Resulting from Use of Hoverboards: Safety Concerns With an Unregulated Consumer Product.
Hoverboards were recently introduced to the US consumer market and experienced rapid popularity. Given the high frequency of musculoskeletal injury with other wheeled recreation devices, we sought to analyze hoverboard injuries in children. A retrospective review of patients with musculoskeletal injury related to hoverboard use was performed at a tertiary care children's hospital. From November 2015 to January 2016, 2.3% of all fractures were related to hoverboards. Common injury mechanisms were fall (79%) and finger entrapment between wheel and wheel-well (10%). The most frequently fractured sites included the distal radius (43%) and phalanx (17%). Common surgical procedures were nailbed repair and pinning for Seymour fracture and percutaneous pinning for distal radius fracture. There exists high risk for distal radius fractures from falls and phalanx fractures from finger entrapment between the wheel and wheel-well. Hoverboard safety can be improved with regular use of wrist guards and improved wheel-well design.


Is dry eye an environmental disease?
Previous studies have revealed that eye contact with either air pollutants or adverse indoor and/or outdoor environmental conditions can affect tear film composition and ocular surface components. These effects are mediated by selective binding of the environmental agents to ocular surface membrane receptors, leading to activation of pro inflammatory signaling pathways. The aim of the current review was to examine the published evidence associated with environmental factors and ocular surface disease and dry eye. Specifically, the reader will appreciate why it is possible to refer to them as mediators of Environmental Dry Eye Disease (EDED), a singular clinical entity inside DED context, directly caused by pollutants and/ or adverse climatic conditions. The indicators and clinical findings are described along with EDE differential diagnosis in its acute and the chronic phases. Based on strong existing evidence of clinical reports and epidemiological observations regarding DED and environmental factors we conclude that there is a straight cause-and-effect relationship between ambient stresses and DED. International standards and web-based tools are described for monitoring worldwide environmental conditions referring localities and populations susceptible to EDED. This information is beneficial to health providers to pinpoint the individuals and predisposed groups afflicted with DED. Such insights may not only improve the understanding and treatment of DED but also help to identify the contributing factors and lower the frequency and progression of EDED.


Course of skin symptoms and quality of life in children referred for patch testing--a long-term follow-up study.
Children are patch tested in the same manner as adults, but little has been done to establish whether positive or negative findings influence the course of skin symptoms. To uncover the course of skin symptoms and the impact of persistent eczema on life quality in paediatric patients referred for patch testing, a retrospective questionnaire was sent to children and adolescents referred for patch testing during a 9-year period. Persistent eczema at follow-up was strongly associated to atopic dermatitis, but was not explained by gender, age, contact allergy or time span from patch testing to follow-up. Among patients without atopic dermatitis, 23.5% reported to suffer from chronic eczema. Persistent eczema increased the risk of severe impairment of life quality. Our findings indicate a significant risk of childhood eczema becoming chronic and affecting life quality considerably. Patch testing did not affect the course of eczema, highlighting the difficulties of avoidance behaviour.


Protein corona formation and its influence on biomimetic magnetite nanoparticles.
Biomimetic magnetite nanoparticles (BMNPs) synthesized in the presence of MamC, a magnetosome-associated protein from Magnetoccus marinus MC-1, have gained interest for biomedical applications because of their unique magnetic properties. However, their behavior in biological systems, like their interaction with proteins, still has to be evaluated prior to their use in clinics. In this study, doxorubicin (DOXO) as a model drug was adsorbed onto BMNPs to form nanoassemblies. These were incubated with human plasma to trigger protein corona (PC) formation. Proteins from the human plasma stably attached to either BMNPs or DOXO-BMNP nanoassemblies. In particular, fibrinogen was detected as the main component in the PC of DOXO-BMNPs that potentially provides advantages, e.g. protecting the particles from phagocytosis, thus prolonging their circulation time. Adsorption of PC to the BMNPs did not alter their magnetic properties but improved their colloidal stability, thus reducing their toxicity in human macrophages. In addition, PC formation enhanced cellular internalization and did not interfere with DOXO activity. Overall, our data indicate that the adsorption of PC onto DOXO-BMNPs in biological environment even increases their efficiency as drug carrier systems.


Adhesion to oviduct glycans regulates porcine sperm Ca2+ influx and viability.
Before fertilization, sperm bind to epithelial cells of the oviduct isthmus to form a reservoir that regulates sperm viability and capacitation. The sperm reservoir maintains optimum fertility in species, like swine, in which semen deposition and ovulation may not be well synchronized. We demonstrated previously that porcine sperm bind to two oviductal glycan motifs, a biantennary 6-sialylated N-acetyllactosamine (bi-SiaLN) oligosaccharide and 3-O-sulfated Lewis X trisaccharide (suLeX). Here, we assessed the ability of these glycans to regulate sperm Ca2+ influx, capacitation and affect sperm lifespan. After 24 h, the viability of sperm bound to immobilized bi-SiaLN and suLeX was higher (46% and 41% respectively) compared to viability of free-swimming sperm (10-12%). Ca2+ is a central regulator of sperm function so we assessed whether oviduct glycans could affect the Ca2+ influx that occurs during capacitation. Using a fluorescent intracellular Ca2+ probe, we observed that both oviduct glycans suppressed the Ca2+ increase that occurs during capacitation. Thus, specific oviduct glycans can regulate intracellular Ca2+. Because the increase in intracellular Ca2+ was suppressed by oviduct glycans, we examined whether glycans affected capacitation, as determined by protein tyrosine phosphorylation and the ability to undergo a Ca2+ ionophore-induced acrosome reaction. We found no discernable suppression of capacitation in sperm bound to oviduct glycans. We also detected no effect of oviduct glycans on sperm motility during capacitation. In summary, LeX and bi-SiaLN glycan motifs found on oviduct oligosaccharides suppress the Ca2+ influx that occurs during capacitation and extend sperm lifespan but do not affect sperm capacitation or motility.


Cel48A from Thermobifida fusca: structure and site directed mutagenesis of key residues.
Lignocellulosic biomass is a potential source of sustainable transportation fuels, but efficient enzymatic saccharification of cellulose is a key challenge in its utilization. Cellulases from the glycoside hydrolase (GH) family 48 constitute an important component of bacterial biomass degrading systems and structures of three enzymes from this family have been previously published. We report a new crystal structure of TfCel48A, a reducing end directed exocellulase from Thermobifida fusca, which shows that this enzyme shares important structural features with the other members of the GH48 family. The active site tunnel entrance of the known GH48 exocellulases is enriched in aromatic residues, which are known to interact well with anhydroglucose units of cellulose. We carried out site-directed mutagenesis studies of these aromatic residues (Y97, F195, Y213, and W313) along with two non-aromatic residues (N212 and S311) also located around the tunnel entrance and a W315 residue inside the active site tunnel. Only the aromatic residues located around the tunnel entrance appear to be important for the ability of TfCel48A to access individual cellulose chains on bacterial cellulose (BC), a crystalline substrate. Both Trp residues were found to be important for the processivity of TfCel48A on BC and phosphoric acid swollen cellulose (PASC), but only W313 appears to play a role in the ability of the enzyme to access individual cellulose chains in BC. When acting on BC, reduced processivity was found to correlate with reduced enzyme activity. The reverse, however, is true when PASC is the substrate. Presumably, higher density of available cellulose chain ends and the amorphous nature of PASC explain the increased initial activity of mutants with lower processivity.


[The tomitsid treatment of chronic cystitis in children].
The clinical efficiency of tomicid used in the treatment of childhood cystitis was examined by employing clinical, endoscopic, microbiological, and immunological findings. A total of 140 children were examined. These include 78 with chronic obstructive pyelonephritis without cystitis and 62 with chronic cystitis. The urinary bladder was instilled with reference tomicid solution in 18 children with chronic cystitis during 10-12 days. Tomicid was found to produce bactericidal and anti-inflammatory effects. The immunomodulating effect was shown mainly in young children (aged 1-6 years). The lack of toxic and adverse effects of the drug allows one to recommend for use in pediatric urologic practice.


Thrombolytic effects in vivo of nattokinase in a carrageenan-induced rat model of thrombosis.
Nattokinase is a serine protease produced by Bacillus subtilis during the fermentation of the soybean product natto. The fibrinolytic activity and thrombolytic effects of nattokinase have been observed in vitro, but the effect in vivo has still to be researched. The objective of this study was to demonstrate the activity of nattokinase in vivo. To establish a rat model of thrombosis, κ-carrageenan was injected subcutaneously into the toes of Sprague-Dawley (SD) rats. Histological examination confirmed thrombosis. The rats were then treated with varying doses of nattokinase and the resulting thrombolysis was histologically assessed. ELISA was used to determine the levels of the fibrin/fibrinogen degradation products (FDPs) and D-dimer, which are sensitive indices of fibrinolytic activity. Vermis kinase, a known thrombolytic agent, was used as a positive control. Biopsy results revealed partial thrombolysis in the tail vessels of the rats treated with nattokinase or vermis kinase. FDP and D-dimer levels were higher in rats treated with high-dose nattokinase than in those treated with saline. No difference in FDP or D-dimer levels was observed between rats treated with high-dose nattokinase and those treated with vermis kinase. Both the histological and physiological evidence from this study indicate that nattokinase exerts thrombolytic effects in vivo.


A Metabolomic Approach to Understanding the Metabolic Link between Obesity and Diabetes.
Obesity and diabetes arise from an intricate interplay between both genetic and environmental factors. It is well recognized that obesity plays an important role in the development of insulin resistance and diabetes. Yet, the exact mechanism of the connection between obesity and diabetes is still not completely understood. Metabolomics is an analytical approach that aims to detect and quantify small metabolites. Recently, there has been an increased interest in the application of metabolomics to the identification of disease biomarkers, with a number of well-known biomarkers identified. Metabolomics is a potent approach to unravel the intricate relationships between metabolism, obesity and progression to diabetes and, at the same time, has potential as a clinical tool for risk evaluation and monitoring of disease. Moreover, metabolomics applications have revealed alterations in the levels of metabolites related to obesity-associated diabetes. This review focuses on the part that metabolomics has played in elucidating the roles of metabolites in the regulation of systemic metabolism relevant to obesity and diabetes. It also explains the possible metabolic relation and association between the two diseases. The metabolites with altered profiles in individual disorders and those that are specifically and similarly altered in both disorders are classified, categorized and summarized.


Relevance of time-dependence for clinically viable diffusion imaging of the spinal cord.
Time-dependence is a key feature of the diffusion-weighted (DW) signal, knowledge of which informs biophysical modelling. Here, we study time-dependence in the human spinal cord, as its axonal structure is specific and different from the brain. We run Monte Carlo simulations using a synthetic model of spinal cord white matter (WM) (large axons), and of brain WM (smaller axons). Furthermore, we study clinically feasible multi-shell DW scans of the cervical spinal cord (b = 0; b = 711 s mm-2 ; b = 2855 s mm-2 ), obtained using three diffusion times (Δ of 29, 52 and 76 ms) from three volunteers. Both intra-/extra-axonal perpendicular diffusivities and kurtosis excess show time-dependence in our synthetic spinal cord model. This time-dependence is reflected mostly in the intra-axonal perpendicular DW signal, which also exhibits strong decay, unlike our brain model. Time-dependence of the total DW signal appears detectable in the presence of noise in our synthetic spinal cord model, but not in the brain. In WM in vivo, we observe time-dependent macroscopic and microscopic diffusivities and diffusion kurtosis, NODDI and two-compartment SMT metrics. Accounting for large axon calibers improves fitting of multi-compartment models to a minor extent. Time-dependence of clinically viable DW MRI metrics can be detected in vivo in spinal cord WM, thus providing new opportunities for the non-invasive estimation of microstructural properties. The time-dependence of the perpendicular DW signal may feature strong intra-axonal contributions due to large spinal axon caliber. Hence, a popular model known as "stick" (zero-radius cylinder) may be sub-optimal to describe signals from the largest spinal axons.


Attitude toward euthanasia scale: psychometric properties and relations with religious orientation, personality, and life satisfaction.
End-of-life decisions (ELDs) represent a controversial subject, with ethical dilemmas and empirical ambiguities that stand at the intersection of ethics and medicine. In a non-Western population, we examined individual differences in perceiving ELDs that end the life of a patient as acceptable and found that an attitude toward euthanasia (ATE) scale consists of 2 factors representing voluntary and nonvoluntary euthanasia. Also, acceptance of ELDs that end the life of a patient negatively correlated with life satisfaction, honesty-humility, conscientiousness, and intrinsic and extrinsic personal motivation toward religion. These findings provided additional construct validity of the ATE scale.


Partition-based and sharp uniform error bounds.
This paper develops probabilistic bounds on out-of-sample error rates for several classifiers using a single set of in-sample data. The bounds are based on probabilities over partitions of the union of in-sample and out-of-sample data into in-sample and out-of-sample data sets. The bounds apply when in-sample and out-of-sample data are drawn from the same distribution. Partition-based bounds are stronger than Vapnik-Chervonenkis (VC) bounds, but they require more computation.


Histamine: metabolism, physiology, and pathophysiology with applications in veterinary medicine.
To review the human and veterinary literature on histamine physiology and pathophysiology and potential applications for clinical use in veterinary critical care. Human and veterinary clinical studies, reviews, texts, and recent research in histamine receptor and antagonist therapy. Recent progress in molecular biology has led to a more complete understanding of the enzymes involved in histamine metabolism and histamine receptor physiology. The past decade of research has confirmed the role of histamine in the classical functions (contraction of smooth muscle, increase in vascular permeability, and stimulation of gastric acid secretion) and has also elucidated newer ones that are now under investigation. Data on the roles of histamine in angiogenesis, circadian rhythm, bone marrow regeneration, bacterial eradication, and cancer are emerging in the literature. Newer histamine antagonists are currently in drug trials and are expected to advance the clinical field in treatment of allergic, gastrointestinal, and cognitive disorders. Veterinary histamine research is directed at identifying the effects of certain pharmacological agents on blood histamine concentrations and establishing the relevance in clinical disease states. Research demonstrates important species differences in regards to histamine receptor physiology and tissue response. Studies in the area of trauma, sepsis, anaphylaxis, allergy, and gastrointestinal disorders have direct applications to clinical veterinary medicine. Histamine plays a key role in the morbidity and mortality associated with allergy, asthma, gastric ulcers, anaphylaxis, sepsis, hemorrhagic shock, anesthesia, surgery, cardiovascular disease, cancer, CNS disorders, and immune-mediated disease. Histamine antagonism has been in common use to block its adverse effects. With recent advances in the understanding of histamine receptor physiology, pharmaceutical agents targeting these receptors have increased the therapeutic options.


Invasion of the pterygoid plates: an indicator for regional lymph node failure in maxillary sinus cancer.
The aim of this study was to evaluate the long-term treatment results of combined superselective intraarterial chemotherapy and radiation therapy for advanced maxillary sinus cancer (MSC) and the incidence of regional lymph node failure, and to reveal the clinical and anatomical predictive factors for metastasis. We retrospectively evaluated 55 consecutive patients with locally advanced squamous cell carcinoma of the maxillary sinus who were treated with external radiotherapy and superselective intraarterial chemotherapy. Elective nodal irradiation (ENI) was performed only in the clinical node-positive (cN+) cases and not in the clinical node-negative (cN0) cases. Thirty-eight patients were cN0, and 17 were cN+ at diagnosis. Regional lymph node metastases occurred in 7 of 38 patients with cN0, and 2 of 17 with cN+ during the median follow-up period of 36 months. There were more cases of high-grade (3 or 4) late adverse events in the ENI group than in the non-ENI group (13% vs. 41%, respectively; p = 0.03). In cN0 cases without ENI, invasion of the pterygoid plates (57% vs. 90%; p < 0.01) and oral cavity (35% vs. 92%, with invasion vs without invasion, respectively; p = 0.02) was significantly correlated with a low 5-year regional recurrence-free rate. Patients with MCS and invasion of the pterygoid plates and oral cavity can be considered appropriate candidates for ENI.


A computer vision-based approach for behavior recognition of gestating sows fed different fiber levels during high ambient temperature.
The objectives of this study were to evaluate convolutional neural network models and computer vision techniques for the classification of swine posture with high accuracy and to use the derived result in the investigation of the effect of dietary fiber level on the behavioral characteristics of the pregnant sow under low and high ambient temperatures during the last stage of gestation. A total of 27 crossbred sows (Yorkshire × Landrace; average body weight, 192.2 ± 4.8 kg) were assigned to three treatments in a randomized complete block design during the last stage of gestation (days 90 to 114). The sows in group 1 were fed a 3% fiber diet under neutral ambient temperature; the sows in group 2 were fed a diet with 3% fiber under high ambient temperature (HT); the sows in group 3 were fed a 6% fiber diet under HT. Eight popular deep learning-based feature extraction frameworks (DenseNet121, DenseNet201, InceptionResNetV2, InceptionV3, MobileNet, VGG16, VGG19, and Xception) used for automatic swine posture classification were selected and compared using the swine posture image dataset that was constructed under real swine farm conditions. The neural network models showed excellent performance on previously unseen data (ability to generalize). The DenseNet121 feature extractor achieved the best performance with 99.83% accuracy, and both DenseNet201 and MobileNet showed an accuracy of 99.77% for the classification of the image dataset. The behavior of sows classified by the DenseNet121 feature extractor showed that the HT in our study reduced (p < 0.05) the standing behavior of sows and also has a tendency to increase (p = 0.082) lying behavior. High dietary fiber treatment tended to increase (p = 0.064) lying and decrease (p < 0.05) the standing behavior of sows, but there was no change in sitting under HT conditions.


Identification and quantification of caffeoylquinic acids and flavonoids from artichoke (Cynara scolymus L.) heads, juice, and pomace by HPLC-DAD-ESI/MS(n).
A method for the identification and quantification of phenolic compounds from artichoke (Cynara scolymus L.) heads, juice, and pomace by HPLC with diode array and mass spectrometric detection was developed. Among the 22 major compounds, 11 caffeoylquinic acids and 8 flavonoids were detected. Quantification of individual compounds was carried out by external calibration. Apigenin 7-O-glucuronide was found to be the major flavonoid in all samples investigated. 1,5-Di-O-caffeoylquinic acid represented the major hydroxycinnamic acid, with 3890 mg/kg in artichoke heads and 3269 mg/kg in the pomace, whereas in the juice 1,3-di-O-caffeoylquinic acid (cynarin) was predominant, due to the isomerization during processing. Total phenolic contents of approximately 12 g/kg on a dry matter basis revealed that artichoke pomace is a promising source of phenolic compounds that might be recovered and used as natural antioxidants or functional food ingredients.


[Somatic mutations of the P53 gene in stomach cancer].
The paper deals with a study of p53 gene somatic mutations in tumor cell genomes from patients with stomach cancers of different histological patterns. It used sequential and molecular cloning methods. The former involved amplicones characterized by abnormal volatility following SSCP analysis of plasmids from 9 tumors. Replacement nucleotides were identified in 4 tumors (intestinal--2, diffuse--2). Among 8 mutations were 1 single-nucleotide deletion in codon-249 with shifting sensing frame and one targeted mutation. Five of the former were missens-mutations which caused amino acid replacement while the other two silent mutations did not. Exon-assisted analysis of p53 ("wild") gene identified cells with stable structure in each tumor (1 mutation--2; 3 mutations--2 including genuinely-paired mutations in 1 exon). All mutations occurred in structurally and functionally important codons. Our evidence corroborated earlier data of SSCP analysis on tumor cell presence in populations with variable p53 genomes.


Predictive validity of the SOCRATES in a clinical sample of Latina/o adolescents.
The Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) is a widely used measure of a client's motivation to change their substance use behavior. It is comprised of 3 subscales, recognition, ambivalence, and taking steps, which correspond to one's awareness, uncertainty, and behavior relative to their substance use. Typically the measure has been examined in adult treatment samples, whereas less attention has been paid to its use with adolescents, especially racial/ethnic minority youth. The purpose of the current study was to test the predictive validity of the SOCRATES subscales on posttreatment substance use levels with a clinical sample of Latina/o adolescents (N = 105) in substance use treatment. Hypotheses were tested via generalized linear models for each of the 3 subscales. Results indicated that higher scores on the Taking Steps subscale of the SOCRATES at pretreatment were predictive of lower days of substance use after treatment for adolescents in the sample. Implications of the results and suggestions for future research are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).