Vitamin E requirement in relation to dietary fish oil and oxidative stress in elderly.
A growing body of evidence shows that oxygen radicals and other products of free radical reactions are involved in aging and age-related degenerative diseases. Recent studies have suggested that fish oils (FO) have a potentially beneficial effect on age-associated diseases. Consumption of FO may increase requirement for vitamin E, especially under conditions where oxidative stress is increased. Vitamin E requirement increases with increased intake of dietary polyunsaturated fatty acids (PUFA). This relationship may be exaggerated in elderly subjects. Our studies, as well as those of others, have shown that plasma lipid peroxides are significantly higher in older subjects compared to young subjects. Thus, in conditions where the percentage of highly unsaturated fatty acid increases in the membrane, older subjects may be more susceptible to oxidative damage. In a series of human studies, we found that older women, receiving FO supplements for 3 months exhibited a greater increase in plasma PUFA compared to young subjects. By substituting membrane fatty acids with the potentially unstable (n-3) fatty acids of FO, older subjects were found to be at greater risk of oxidative stress than young subjects. In addition, when exposed to eccentric exercise-induced oxidative stress, older men, receiving vitamin E supplements for 48 days, exhibited significantly lower levels of lipid peroxides in urine compared to placebo control. These data indicate that older subjects are more susceptible to oxidative stress and may benefit from the antioxidant protection provided by vitamin E.


Isolation, chemical characterization, and biophysical properties of three different abnormal lipoproteins: LP-X1, LP-X2, and LP-X3.
Three different but related abnormal lipoprotein species, LP-X1, LP-X2, and LP-X3, have been isolated from cholestatic plasma by ethanol precipitation and zonal ultracentrifugation. All three populations are rich in phospholipids (64.9 to 67.5%) and cholesterol (23.0 to 26.8%) but poor in cholesteryl esters (0.4 to 1.9%), triglycerides (1.8 to 3.2%), and protein (3.2 to 6.7%) with differences in chemical composition which result in buoyant densities (1.038, 1.049, and 1.058, respectively) to allow their separation. LP-X1, LP-X2, and LP-X3 exhibited apparent flotation rates of 17.3, 9.7, and 3.2 Svedbergs and Stokes radii of 339, 343, and 294 A, respectively. As determined from circular dichroic measurements, the protein constituents of all three particles possessed a high degree of alpha helical structure (41 to 65%). Each LP-X particle exhibited abnormally low fluidity as evaluated by electron paramagnetic resonance. All of the particles contained human serum albumin and the C-proteins as major protein constituents, but only LP-X2 and LP-X3 contained apolipoprotein A-I and apolipoprotein E.


Unusual metastatic chondrosarcoma detected with bone scintigraphy.
A case is presented of a scapular chondrosarcoma which showed intense uptake of Tc99m MDP in the primary tumour and in pleural and osseous metastases. Additionally, there was intense visualization of the malignant pleural effusion. The bone scintigraphy correctly diagnosed the extent of the involvement. This finding is unusual because chondrosarcomas in such a disseminated state are relatively rare.


Perspectives on barriers and facilitators to mental health support after a traumatic birth among a sample of primarily White and privately insured patients.
To elicit the perspectives of individuals with a traumatic birth experience on barriers and facilitators to receiving mental health support in the postpartum period. Individuals who experienced a traumatic birth within the last three years (n = 32) completed semi-structured phone interviews about their birth and postpartum experience. The Post-traumatic Stress Disorder Checklist for DSM-V (PCL-5), Patient Health Questionnaire (PHQ-8), and Generalized Anxiety Disorder scale (GAD-7) were administered. Qualitative data was analyzed using a modified grounded theory by three independent coders. Among participants, 34.4% screened positive for PTSD, 18.8% for depression, and 34.4% for anxiety. Participants described multi-level barriers that prevented clinicians from recognizing and supporting patients' postpartum mental health needs; those involved lack of communication, education, and resources. Recommendations from participants included that 1) obstetric professionals should acknowledge birth-related trauma experienced by any individual, 2) providers of multiple disciplines need to be integrated into postpartum care, and 3) mental health support may be needed before the ambulatory postpartum visit. There are multi-level barriers towards detecting and responding to individuals' mental health needs after a traumatic birth. Obstetric professionals need to use a trauma-informed approach and proactively assess mental health throughout the postpartum period.


Experimentally produced sinusoidal fetal heart rate pattern in the chronically instrumented fetal lamb.
A sinusoidal fetal heart rate and elevated fetal arginine vasopressin levels were found in two bled fetal lambs. Arginine vasopressin was continuously infused intravenously in chronically instrumented fetal lambs at rates ranging between 1.0 and 90 mlU/kg/min. No sinusoidal heart rate occurred in 21 experiments on six control animals with intact vagal nerves. Atropine at doses less than 0.4 mg had no effect (six experiments on three animals). Higher doses of atropine (greater than 1.2 mg) resulted in sinusoidal heart rate (24 experiments on six animals). Twenty-three infusions were performed in five bilaterally vagotomized fetuses, and the sinusoidal heart rate was successfully induced in 17 experiments. The arginine vasopressin infusion rate was less than 1.5 mlU/kg/min on the six occasions in which the sinusoidal heart rate did not appear. All sinusoidal heart rate patterns were associated with fluctuation of fetal arterial pressure at the same frequency. There was a linear correlation between the amplitude of sinusoidal heart rate and magnitude of arterial blood pressure fluctuation. The amplitude of sinusoidal heart rate increased with the concentration of arginine vasopressin infused. Modification of sinusoidal heart rate pattern was attempted with use of sympathetic agonists and antagonists. The possible etiology and mechanisms of sinusoidal heart rate pattern are discussed.


Non-contrast MR angiography of pelvic arterial vasculature using the Quiescent interval slice selective (QISS) sequence.
To evaluate Quiescent Interval Slice Selective (QISS) balanced steady-state free precession (bSSFP) and QISS fast low-angle shot (FLASH) sequences for non-contrast Magnetic Resonance Angiography (MRA) of iliac arteries regarding image quality and diagnostic confidence in order to establish these sequences in daily clinical practice. A prospective study of healthy subjects (n = 10) was performed. All subjects underwent the QISS MRI protocol with bSSFP und FLASH sequences. Vessel contrast-to-background ratio (VCBR) were measured in pre-defined vessel segments. Image quality and diagnostic confidence was assessed using a Likert scale (five-point scale). Inter-reader agreement was determined using Cohen's kappa coefficient (κ). Ten healthy subjects (median age 29 years, IQR: 26.25 to 30 years) were included in this prospective study. Median MR examination time was 2:05 min (IQR 1:58 to 2:16) for QISS bSSFP and 4:11 min (IQR 3:57 to 4:32) for QISS FLASH. Both sequences revealed good VCBR in all examined vessel segments. VCBR (muscle tissue) were marginally higher for FLASH sequences (e.g., 0.82 vs. 0.78 in the right femoral artery, p = 0.035*), while bSSFP sequence showed significantly higher VCBR (fat tissue) in the majority of examined arterials vessels (e.g., 0.78 vs. 0.62 in right femoral artery, p = 0.001*). The image quality and diagnostic confidence of both sequences were rated as good to excellent. Moderate to good inter-reader agreement was found. QISS MRA using bSSFP and FLASH sequences are diagnostic for visualization of iliac arterial vasculature. The QISS bSSFP sequence might offer advantages due to the markedly shorter exam time and superior visualization of smaller vessels. The QISS FLASH sequence seems to be a robust alternative for non-contrast MRA since it is less sensitive to magnetic field inhomogeneities.


The challenge of upper airway obstruction in pediatric intensive care.
Over a 5-year period, 75 patients were admitted to a pediatric intensive care unit because of acute upper airway obstruction (AUAO). Congenital abnormalities were demonstrated in 25 children; 9 of them died secondary to severe combined malformations or major central nervous system dysfunction. Acquired AUAOs were seen in 50 patients; 1 died in brain death secondary to anoxia. Obstructions were observed at all levels of the airways from the nose to the carina. In 28% of the patients, AUAO had remained undiagnosed until admission for complications such as acute respiratory failure, cardiac arrest, coma, seizures. With early diagnosis and prompt release of the obstruction the prognosis is good unless severe congenital abnormalities or major central nervous system damage are associated.


Capacitation in vitro of bovine spermatozoa by oviduct epithelial cell monolayer conditioned medium.
The effect of the active capacitating factor secreted from oviduct epithelial cell monolayers (OECM) in different environments on in vitro fertilization was evaluated. Capacitation was determined as the ability of sperm to fertilize bovine oocytes in vitro. When the mTALP was supplemented with glucose during conditioning, the sperm penetration rate was significantly reduced (P < 0.05) compared to the control (7% +/- 1 vs. 30% +/- 4). The percentages of sperm penetrated oocytes were higher following insemination in the OECM-conditioned medium derived from the early stage (48% +/- 7) of the estrous cycle than in the OECM-conditioned medium derived from either mid (35% +/- 2) or late stages (28% +/- 3) of the estrous cycle. When the medium was supplemented with 0.1 or 0.5 microgram/ml estradiol-17 beta during medium conditioning, sperm penetration rates increased (P < 0.05) compared to the control group (55% +/- 4 vs. 40% +/- 3 and 54% +/- 2 vs. 41% +/- 3, respectively). In addition, the percentages of penetrated oocytes significantly decreased (P < 0.05) following insemination when the OECM-conditioned medium was added to 0.01%, 0.05%, and 0.1% ethanol compared to the control (25% +/- 4, 19% +/- 2, 18% +/- 3, and 45% +/- 3, respectively). Sperm penetration rates significantly (P < 0.01) decreased when the OECM-conditioned medium was heated to 100 degrees C for 5 min (10% +/- 1 vs. 40% +/- 3). These results suggest that the active capacitating factor was secreted by the OECM and that this capacitating factor in the OECM-conditioned medium was inhibited by the presence of glucose. This factor was found to be heat-sensitive and its action was affected by ethanol. The OECM derived from the three phases of the estrous cycle as well as the presence of estradiol-17 beta influenced the capacity of the OECM to secrete this capacitating factor in vitro.


A novel SYNE1 gene mutation in a Chinese family of Emery-Dreifuss muscular dystrophy-like.
In the present study, a novel mutation in exon 46 at codon 2304 (G2304R) of the SYNE1 gene is described in a Chinese family (proband, mother, and sister) with Emery-Dreifuss muscular dystrophy-like, which clinically manifests as muscle weakness, muscle atrophy, joint contracture, and without significant cardiac abnormalities. Clinical examination and neuroimaging of the captured target region and high-throughput sequencing were performed in a family of four generations. Muscle changes were evaluated using magnetic resonance imaging and muscle biopsies. Target region capture sequencing yielded a novel missense mutation in codon 2304 (G2304R), which is a heterozygous A to G point mutation at position 6910 (c.6910A > G) in exon 46 of SYNE1 leading to a glycine-to-arginine substitution (p.Gly2304Arg). The results were also identified by Sanger sequencing in three family members but not in the other three unaffected family members and 100 control subjects. This mutation is probably pathogenic and is the first of its kind reported in a familial Emery-Dreifuss muscular dystrophy-like.


Efficiency of different sanitation methods on Listeria monocytogenes biofilms formed under various environmental conditions.
The resistance of Listeria monocytogenes biofilms formed under food processing conditions, against various sanitizing agents and disinfection procedures was evaluated in the present study. The first sanitation procedure included biofilm formation on stainless steel coupons (SS) placed in tryptic soy broth supplemented with 0.6% yeast extract (TSBYE) of various concentrations of NaCl (0.5, 7.5 and 9.5%) at different temperatures (5 and 20 °C). The biofilms formed were exposed to warm (60 °C) water for 20 min, or to peroxyacetic acid (2% PAA) for 1, 2, 3 and 6 min. Treatment with warm water caused no significant (P ≥ 0.05) reductions in the attached populations. Conversely, surviving bacteria on SS coupons decreased as the exposure time to 2% PAA increased and could not be detected by culture after 6 min of exposure. Biofilms formed at 20°C were more resistant to PAA than biofilms formed at 5 °C. Salt concentration in the growth medium had no marked impact on the resistance to PAA. The second sanitation procedure included biofilm formation of nonadapted (NA) and acid-adapted (AA) cells in TSBYE of pH 5.0 and 7.0 (i.e., NA-5.0, NA-7.0 and AA-5.0, AA-7.0) at 4 °C. Coupons bearing attached cells of L. monocytogenes were periodically exposed to chlorine (0.465% Cl(-)), quaternary ammonium compound (1% QAC) and 2% PAA. The resistance of attached cells to QAC, PAA and Cl(-) followed the order: AA-5.0>NA-7.0 ≥ AA-7.0>NA-5.0. The most effective sanitizer was QAC followed by PAA and Cl(-). The results can lead to the development of efficient sanitation strategies in order to eliminate L. monocytogenes from the processing environment. Furthermore, such results may explain the presence of L. monocytogenes after sanitation as a result of cell attachment history.


Influenza vaccination among persons with work-related asthma.
Seasonal influenza vaccination is recommended for all asthma patients. Persons with work-related asthma may have more severe disease than those with non-work-related asthma and may particularly benefit from receiving influenza vaccination. To determine if influenza vaccination coverage differs among individuals aged 18-64 years with work-related and non-work-related asthma. Data from the 2006-2009 Behavioral Risk Factor Surveillance System Asthma Call-Back Survey collected in 38 states and the District of Columbia were analyzed in 2013. Multivariable logistic regression and predictive marginal analyses were conducted to identify factors independently associated with influenza vaccination among respondents aged 18-64 years with work-related asthma. Among adults aged 18-64 years with current asthma, an estimated 42.7% received influenza vaccination in the past 12 months. Although influenza vaccination coverage was significantly higher among adults with work-related asthma than those with non-work-related asthma (48.5% vs 42.8%), this association became non-significant after adjustment for demographic and clinical characteristics (prevalence ratio=1.08, 95% CI=0.99, 1.20). Among individuals with work-related asthma, receiving the influenza vaccine was associated with being 50-64 years old, being unemployed in the prior year, and seeking urgent treatment for worsening asthma symptoms. Among persons with work-related and non-work-related asthma, less than half received influenza vaccination in the prior year, both below the Healthy People 2010 target of 60%. These results suggest the need for strengthening current vaccination interventions to meet the updated Healthy People 2020 objective of achieving at least 70% influenza vaccination coverage.


Chalcogen Bonding Catalysis of a Nitro-Michael Reaction.
Chalcogen bonding is the non-covalent interaction between Lewis acidic chalcogen substituents and Lewis bases. Herein, we present the first application of dicationic tellurium-based chalcogen bond donors in the nitro-Michael reaction between trans-β-nitrostyrene and indoles. This also constitutes the first activation of nitro derivatives by chalcogen bonding (and halogen bonding). The catalysts showed rate accelerations of more than a factor of 300 compared to strongly Lewis acidic hydrogen bond donors. Several comparison experiments, titrations, and DFT calculations support a chalcogen-bonding-based mode of activation of β-nitrostyrene.


An investigation of the information provided to the parents of young people with mental health needs on an internet forum.
Access to Children and Adolescent Mental Health Services (CAMHS) can be difficult, with lengthy wait times. Many of the young people and their parents are not signposted to any form of support during their wait for initial assessment or treatment and people are increasingly turning towards web-based resources for help and advice. However, there are some concerns about the quality of the information shared online. Research on the use and quality of information shared on online platforms for mental health inquiries is limited. We aimed to investigate the content and quality of the responses shared by forum users on an online forum for parents of young people with mental health needs (Mumsnet 'Talk'). Forum users were primarily parents, but 8 posts were written by posters identifying as a healthcare worker, teacher, or autism spectrum specialist. Qualitative methodology was adopted for this study. Forum content from Mumsnet was extracted in an anonymised form and thematic analysis was conducted to explore the content. Information shared in the online forum was assessed for quality by comparing the responses with clinical guidelines. Thread topics related to 16 mental health problems. "Autistic Traits/Autism Spectrum Disorder", "Obsessions and Intrusive Thoughts/ Obsessive Compulsive Disorder" and "Comorbid Anxiety and Depression" were the most prevalent thread topics, consisting 38.3% of the extracted content. The investigation focused on "Information Offered" as the general dimension. Based on the thematic analysis, there were four second-order themes regarding the information offered by forum users; referral, advice, anecdotal information and opinion on case. The quantitative assessment of responses found that 58.3% of the knowledge exchange on Mumsnet was congruent with evidence-based clinical guidelines. Themes indicate that parents of children and young people with mental health needs seem to use online fora for informational support. It is promising that a significant proportion of the information shared within the extracted forum content is congruent with evidence-based knowledge. However, further investigation is needed to generate better understanding of the overall quality of mental health information available on online platforms.


Association of prednisone and antinuclear antibodies with pregnancy outcomes in women with unexplained recurrent pregnancy loss.
To investigate the therapeutic role of prednisone in patients having unexplained recurrent pregnancy loss (URPL) with positivity of antinuclear antibodies (ANA) and the relationship between ANA titers, prednisone, and pregnancy outcomes. We included 202 women diagnosed as having URPL with positive ANA at titer of 1:80 or more. Among them, 159 patients receiving prednisone plus aspirin were included as group PA and the remaining 43 patients prescribed aspirin only served as group A. Live birth rates were considered as the primary outcome. Incidence rates of pregnancy complications and outcomes of the newborns were also compared. Additionally, the association between live birth and major clinical variables was studied. Live birth rates were comparable between the two groups (93.1% versus 83.7%, P = 0.107). No significant differences were observed regarding the incidence rates of adverse pregnancy outcomes, other pregnancy complications and the fetal outcomes. Alteration of ANA titers after pregnancy compared with pre-conception results was the only significant variable associated with live birth. Prednisone plus aspirin did not show improved therapeutic effects over aspirin alone in URPL patients with positive ANA. Variation of ANA titers was found to be a prognostic indicator of pregnancy outcomes in these patients.


Implementation of Vaccinomics and In-Silico Approaches to Construct Multimeric Based Vaccine Against Ovarian Cancer.
One of the most common gynecologic cancers is ovarian cancer and ranked third after the other two most common cancers: cervical and uterine. The highest mortality rate has been observed in the case of ovarian cancer. To treat ovarian cancer, an immune-informatics approach was used to design a multi-epitope vaccine (MEV) structure. Epitopes prediction of the cancer testis antigens (NY-ESO-1), A-Kinase anchor protein (AKAP4), Acrosin binding protein (ACRBP), Piwi-like protein (PIWIL3), and cancer testis antigen 2 (LAGE-1) was done. Non-toxic, highly antigenic, non-allergenic, and overlapping epitopes were shortlisted for vaccine construction. Chosen T-cell epitopes displayed a robust binding attraction with their corresponding Human Leukocyte Antigen (HLA) alleles demonstrated 97.59% of population coverage. The vaccine peptide was established by uniting three key constituents, comprising the 14 epitopes of CD8 + cytotoxic T lymphocytes (CTLs), 5 helper epitopes, and the adjuvant. For the generation of the effective response of CD4 + cells towards the T-helper cells, granulocyte-macrophage-colony-stimulating factor (GM-CSF) was applied. With the addition of adjuvants and linkers, the construct size was 547 amino acids. The developed MEV structure was predicted to be antigenic, non-toxic, non-allergenic, and firm in nature. I-tasser anticipated the 3D construction of MEV. Moreover, disulfide engineering further enhanced the stability of the final vaccine protein. In-silico cloning and vaccine codon optimization were done to analyze the up-regulation of its expression. The outcomes established the vaccine's immunogenicity and safety profile, besides its aptitude to encourage both humoral and cellular immune responses. The offered vaccine, grounded on our in-silico investigation, may be considered for ovarian cancer immunotherapy. The online version contains supplementary material available at 10.1007/s10989-021-10294-w.


Prescribed performance model-free adaptive sliding mode control of a shape memory alloy actuated system.
This paper concentrates on a simple and robust control method for the discrete time nonlinear systems to fulfill the requirement of predefined accuracy. A sliding mode control method is designed by introducing equivalent dynamic linearization technique according to the input/output (I/O) information merely. A square-root type error transformation method is presented for the tracking error to be restricted within a preassigned zone. The performance of presented control method is demonstrated through experiments on a nonlinear system. Experiment results show that the presented control method has a superior tracking accuracy compared with PID controller and model-free adaptive control (MFAC).


Placental morphology and concentrations of glutathione (GSH and GSSG) and lipid peroxides (LPO) in two models of disturbed pregnancy of Uje:WIST rats.
Treatment of pregnant rats with heat-denaturated bacterial material (endotoxin-model) or exposure to chronic restraint of prenatally lithium-treated pregnant dams (stress-model) were used as two models of disturbed pregnancy, both causing decreased fetal body mass. The quotient of fetal/placental mass was lowered in the endotoxin-group only. Placental mass and protein content were not changed significantly in both experimental groups, although a tendency to smaller placentae was noticed in the stress-group. Placental histology of the stress-group did not differ from untreated controls. In the endotoxin-group an altered structure of the placental barrier was observed. Small decreases of GSH and GSSG in the endotoxin-group and of GSSG in the stress-group without significant changes of the GSH/GSSG relationship were measured in homogenates of the placental labyrinth. Moderate enhancement of LPO concentration occurred in the endotoxin-group and more distinctly in two litters of the stress-group, the latter being connected with high GSSG concentrations and low fetal/placental mass-quotients.


Clinical study of oral administration of DN-1417, a TRH analog, in patients with intractable epilepsy.
An open dose-finding trial of orally administered DN-1417 was undertaken to investigate dose, efficacy, and adverse reactions. One hundred ninety patients, with epilepsy resistant to conventional drug treatment, were randomly allocated to two treatment groups of low dose (20 mg/day for adult) and high dose (80 mg/day for adult). Medication was given while fasting, once a day, for 8 weeks. If at the end of the first 4-week treatment period the patient had a satisfactory response, the dose was doubled. Patient response was assessed by global improvement rating (GIR) based on changes in seizure frequency, EEG findings, and nonparoxysmal clinical manifestations. The responses assessed by GIR was "slightly to markedly improved" in 48% of the patients with low-dose treatment and 55% with high-dose treatment. There was no clear dose-related difference between the two treatments. In patients with Lennox-Gastaut syndrome having no history of West syndrome, the rate of response assessed by GIR was found to be slightly dose-related (low dose, 61%; high dose, 73%).


Fission yeast MO25 protein is localized at SPB and septum and is essential for cell morphogenesis.
Cell morphogenesis is of fundamental significance in all eukaryotes for development, differentiation, and cell proliferation. In fission yeast, Drosophila Furry-like Mor2 plays an essential role in cell morphogenesis in concert with the NDR/Tricornered kinase Orb6. Mutations of these genes result in the loss of cell polarity. Here we show that the conserved proteins, MO25-like Pmo25, GC kinase Nak1, Mor2, and Orb6, constitute a morphogenesis network that is important for polarity control and cell separation. Intriguingly, Pmo25 was localized at the mitotic spindle pole bodies (SPBs) and then underwent translocation to the dividing medial region upon cytokinesis. Pmo25 formed a complex with Nak1 and was required for both the localization and kinase activity of Nak1. Pmo25 and Nak1 in turn were essential for Orb6 kinase activity. Further, the Pmo25 localization at the SPBs and the Nak1-Orb6 kinase activities during interphase were under the control of the Cdc7 and Sid1 kinases in the septation initiation network (SIN), suggesting a functional linkage between SIN and the network for cell morphogenesis/separation following cytokinesis.


High-Efficiency Reverse (5'→3') Synthesis of Complex DNA Microarrays.
DNA microarrays are important analytical tools in genetics and have recently found multiple new biotechnological roles in applications requiring free 3' terminal hydroxyl groups, particularly as a starting point for enzymatic extension via DNA or RNA polymerases. Here we demonstrate the highly efficient reverse synthesis of complex DNA arrays using a photolithographic approach. The method is analogous to conventional solid phase synthesis but makes use of phosphoramidites with the benzoyl-2-(2-nitrophenyl)-propoxycarbonyl (BzNPPOC) photolabile protecting group on the 3'-hydroxyl group. The use of BzNPPOC, with more than twice the photolytic efficiency of the 2-(2-nitrophenyl)-propoxycarbonyl (NPPOC) previously used for 5'→3' synthesis, combined with additional optimizations to the coupling and oxidation reactions results in an approximately 3-fold improvement in the reverse synthesis efficiency of complex arrays of DNA oligonucleotides. The coupling efficiencies of the reverse phosphoramidites are as good as those of regular phosphoramidites, resulting in comparable yields. Microarrays of DNA surface tethered on the 5' end and with free 3' hydroxyl termini can be synthesized quickly and with similarly high stepwise coupling efficiency as microarrays using conventional 3'→5' synthesis.


Diverse heterochromatin states restricting cell identity and reprogramming.
Heterochromatin is defined as a chromosomal domain harboring repressive H3K9me2/3 or H3K27me3 histone modifications and relevant factors that physically compact the chromatin. Heterochromatin can restrict where transcription factors bind, providing a barrier to gene activation and changes in cell identity. While heterochromatin thus helps maintain cell differentiation, it presents a barrier to overcome during efforts to reprogram cells for biomedical purposes. Recent findings have revealed complexity in the composition and regulation of heterochromatin, and shown that transiently disrupting the machinery of heterochromatin can enhance reprogramming. Here, we discuss how heterochromatin is established and maintained during development, and how our growing understanding of the mechanisms regulating H3K9me3 heterochromatin can be leveraged to improve our ability to direct changes in cell identity.


Organ-sparing radiation therapy for head and neck cancer.
To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.


COVID-19 and hyperammonemia: Potential interplay between liver and brain dysfunctions.
Although COVID-19 affects the respiratory system, extrapulmonary manifestations frequently occur, including encephalopathy and liver damage. Here, we want to call attention to a possible connection between liver and brain dysfunctions, in which ammonia can play a role targeting astrocytes. Importantly, astrocyte dysfunction can produce future and/or long-term neurological consequences.


Controlling stereochemistry during oxidative coupling. Preparation of Rp or Sp phosphoramidates from one P-chiral precursor.
Stereochemical outcome of oxidative coupling of H-phosphonate diesters with amines, promoted by iodine, can be controlled to obtain the corresponding phosphoramidate diesters with inversion or with retention of configuration at the phosphorus centre.


Comparative analysis of the safety and tolerability of eslicarbazepine acetate in older (≥60 years) and younger (18-59 years) adults.
To investigate the safety and tolerability of eslicarbazepine acetate (ESL), a once-daily oral anti-seizure drug (ASD), in older and younger adult patient populations. Two post-hoc pooled data analyses were performed: one from three Phase III studies in patients with focal (partial-onset) seizures who were taking 1-3 concomitant ASDs; the other from five Phase II studies in patients from non-epilepsy populations not taking other ASDs chronically and/or at a clinically-effective anti-seizure dose. The frequencies of treatment-emergent adverse events (TEAEs) were calculated for the older (≥60 years) and younger (18-59 years) adults separately. In the focal seizures study pool, 4.1 % of patients (58/1431) were aged ≥60 years. The overall frequency of TEAEs was 77.5 % in older ESL-treated patients and 72.6 % in younger ESL-treated patients (p = 0.495). For patients who received placebo, the overall frequency of TEAEs was 50.0 % in the older adults and 57.5 % in the younger adults (p = 0.531). The overall placebo-adjusted frequency of TEAEs was 27.5 % in older adults and 15.1 % in younger adults. The placebo-adjusted frequencies of the TEAEs dizziness, somnolence, headache, nausea, diplopia, blurred vision, and ataxia were ≥5 % higher, and frequencies of vomiting and vertigo were ≥2 % higher in older than younger adults. The overall frequency of TEAEs leading to discontinuation was 15.0 % in older ESL-treated patients and 17.6 % in younger ESL-treated patients (p = 0.647); the frequency increased with increasing ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 5.6 % in older adults and 6.6 % in younger adults (p = 0.847). In the non-epilepsy study pool, 30.2 % of patients (515/1705) were aged ≥60 years. The overall frequency of TEAEs was 56.9 % in older ESL-treated patients and 58.8 % in younger ESL-treated patients. The placebo-adjusted frequencies were 14.9 % in older and 15.1 % in younger ESL-treated patients. The placebo-adjusted frequencies of the TEAEs nausea, vomiting, fatigue, and vertigo were ≥2 % higher in older adults, whereas somnolence was ≥2 % higher in younger adults. The overall frequency of TEAEs leading to discontinuation was 18.3 % in older ESL-treated patients and 12.1 % in younger ESL-treated patients (p = 0.003); frequencies were not related to ESL dose. For patients who received placebo, the overall frequency of TEAEs leading to discontinuation was 8.0 % in older adults and 5.6 % in younger adults (p = 0.407). Analyses of adverse event data support the safety and tolerability of ESL in adults aged ≥60 years. In the limited number of older patients with focal seizures taking ESL plus concomitant ASDs (n = 40), the frequency of TEAEs was generally higher than in younger adults. However, in the non-epilepsy patient group (in which the number of older patients was ten times larger; 427 patients taking ESL without concomitant ASDs), no marked age-related TEAE differences were observed, suggesting that increased ASD load associated with adjunctive therapy may complicate treatment selection in older patients, due to risk of increased adverse events. As is common practice for all ASDs, balancing clinical response and tolerability is needed in this vulnerable group of patients.


Validating the potential of the International Classification of Functioning, Disability and Health to identify barriers to and facilitators of consumer participation.
Occupational therapists need tools to identify barriers and facilitators to participation in societal roles. The purpose of this study was to examine the potential of the International Classification of Functioning, Disability and Health (ICF) two-level classification for use in occupational therapy. A secondary analysis of an existing dataset was conducted to identify participation barriers and facilitators that mapped to the ICF and those that did not. A broad range of factors was captured across the components of the ICF. Findings also revealed enabling and disabling factors that were not evident in the ICF. The ICF can support the identification of a broad range of external barriers and facilitators relevant to participation and of interest to occupational therapy. However, therapists must use other strategies to gain a comprehensive understanding of the nature, extent and consequences of barriers and facilitators that may exist in a given


A test of altitude-related variation in aerobic metabolism of Andean birds.
Endotherms at high altitude face the combined challenges of cold and hypoxia. Cold increases thermoregulatory costs, and hypoxia may limit both thermogenesis and aerobic exercise capacity. Consequently, in comparisons between closely related highland and lowland taxa, we might expect to observe consistent differences in basal metabolic rate (BMR), maximal metabolic rate (MMR) and aerobic scope. Broad-scale comparative studies of birds reveal no association between BMR and native elevation, and altitude effects on MMR have not been investigated. We tested for altitude-related variation in aerobic metabolism in 10 Andean passerines representing five pairs of closely related species with contrasting elevational ranges. Mass-corrected BMR and MMR were significantly higher in most highland species relative to their lowland counterparts, but there was no uniform elevational trend across all pairs of species. Our results suggest that there is no simple explanation regarding the ecological and physiological causes of elevational variation in aerobic metabolism.


Circuit mechanisms for colour vision in zebrafish.
The use of spectral information in natural light to inform behaviour is one of the oldest and most fundamental abilities of visual systems. It long-predates animals' venture onto the land, and even the appearance of image-forming eyes. Accordingly, circuits for colour vision evolved under the surface of ancient oceans for hundreds of millions of years. These aquatic beginnings fundamentally underpin, and likely constrain, the organisation of modern visual systems. In contrast to our detailed circuit level understanding from diverse terrestrial vertebrates, however, comparatively little is known about their aquatic counterparts. Here, I summarise some of what is known about neural circuits for colour vision in fish, the most species-diverse group of vertebrates. With a focus on zebrafish, I will explore how their computational strategies are linked to the statistics of natural light in the underwater world, and how their study might help us understand vision in general, including in our own eyes.


Mapping the imaginative mind: Charting new paths forward.
The fields of psychology and neuroscience are in the midst of an explosion of research seeking to understand human imagination - the ability to form thoughts and mental images that stretch beyond what is currently available to the senses. Imaginative thought is proving to be remarkably diverse, capturing the capacity to recall past experiences, consider what lies ahead, and understand others' minds, in addition to other forms of creative and spontaneous thinking. In the first part of this article, we introduce an integrative framework that attempts to explain how components of a core brain network facilitate interacting features of imagination that we refer to as the "mind's eye" and "mind's mind." We then highlight three emerging research directions that could inform our understanding of how imagination arises and unfolds in everyday life.


Bioinformatic Analysis of Circular RNA Expression.
Circular RNAs (circRNAs) are stable RNA molecules generated by backsplicing that play regulatory functions through interaction with other RNA and proteins, as well as by encoding peptides. Dysregulation of circRNA expression can drive cancer development and progression with different mechanisms. CircRNAs are currently regarded as extremely attractive molecules in cancer research for the identification of new and possibly targetable disease regulatory networks and for the development of biomarkers for cancer diagnosis, prognosis definition, and monitoring. Using specific experimental and computational protocols, circRNAs can be identified through RNA-seq by spotting the reads spanning backsplice junctions, which are specific to circular molecules. In this chapter, we report a state-of-the-art computational protocol for a genome-wide analysis of circRNAs from RNA-seq data, which considers circRNA detection, quantification, and differential expression testing. Finally, we indicate how to determine circular transcript sequences and the resources for an in silico functional characterization of circRNAs.


Simultaneous porcine circovirus type 2 and Mycoplasma hyopneumoniae co-inoculation does not potentiate disease in conventional pigs.
The aim of this study was to assess the effect of simultaneous experimental inoculation of porcine circovirus type 2 (PCV2; intranasal delivery) and Mycoplasma hyopneumoniae (Mhyo; transtracheal delivery) into conventional, seropositive 6-week-old piglets. Thirty-six male piglets were assigned randomly to four groups: control (n=6), PCV2 (n=6), Mhyo (n=12) and PCV2+Mhyo (n=12). Blood samples and faecal and nasal swabs were collected at 0, 7, 14 and 21 days post inoculation (dpi). No significant clinical signs attributable to PCV2 infection were observed during the experiment. Coughing was recorded in three pigs from the Mhyo group and six from the PCV2+Mhyo group. No significant differences in mean body weight and rectal temperature were observed between the groups. Mild microscopical lesions similar to those reported for post-weaning multisystemic wasting syndrome were observed in two PCV2 pigs and in one PCV2+Mhyo animal. Mhyo-compatible lung lesions were observed in 21/24 pigs inoculated with Mhyo (10 from the Mhyo group and 11 from the PCV2+Mhyo group). PCV2 was detected by in-situ hybridization in 3/12 PCV2 and in 4/12 PCV2+Mhyo animals. No significant differences in PCV2 load (serum and nasal and faecal swabs), duration of viraemia or antibody titre were detected between PCV2-inoculated groups. No significant differences in Mhyo load in nasal swabs, percentage of Mhyo-seropositive pigs and mean lung score was detected between Mhyo-inoculated groups. Under the conditions of the present study, concurrent inoculation of PCV2 and Mhyo did not result in potentiation of clinical signs and lesions attributed to either infection.


Impact of the unplanned excision on the oncological outcomes of patients with soft tissue sarcomas: a single-center retrospective review of 490 patients.
This study aimed to (1) compare the oncological results of patients who underwent re-excision after unplanned excision with those who underwent planned excision and (2) analyze the impact of local recurrences on oncological outcomes. Patients with soft tissue sarcoma who had been treated in our center between 2000 and 2018 were retrospectively reviewed. Patients were divided into two groups: Group PE (Planned excision; n=345) and group UE (Unplanned excision; n=145). Two groups were compared in terms of local recurrence-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS). Local recurrences effects over MFS and OS were also analyzed. There were 26 (17.9%) local recurrences in the UE group and 30 (8.7%) local recurrences in the PE group (P=0.005). There was no difference in MFS and OS between study groups (P=0.278 and P=0.848, respectively). Five years MFS rates of UE and PE groups were 76.4% and 73.6%, and five-year OS rates of UE and PE groups were 70.3% and 73.9%, respectively (P=0.417, P=0.656). Patients with local recurrence had a 1.96 times higher risk of metastasis than patients without local recurrence (P=0.008). Patients with local recurrence had 1.65 times higher risk of mortality than patients without local recurrence (P=0.047). Although local recurrence is much more common in the UE group, this outcome does not seem to affect MFS or OS. These results indicate that similar outcomes can be achieved if UE patients are referred and appropriately treated with wide re-resections. Level III, Therapeutic Study.


Tissue residues from subacute oral feeding of polychlorinated biphenyl dielectric fluids.
The results of this study can be summarized as follows: (1) Monochlorobiphenyl and the 30%-chlorinated biphenyl MCS 1043 did not accumulate in the lipid reservoir of the rats when fed at 25 ppm and 100 ppm in the diet. This result indicates that mono-, di-, and trichlorobiphenyls are readily metabolized and/or excreted under the conditions of this study. (2) Although a fraction of the ingested Aroclor 1242 and Aroclor 1016 was stored in the rats' lipid reservoir, most of this residue was depleted after the rats had been on the basal laboratory diet for several weeks. (3) Residues of Aroclor 1016 accumulated more slowly and to a significantly lesser extent than those of Aroclor 1242. During the recovery period these PCB residues decreased to lower values for Aroclor 1016. This result indicates that a product containing reduced amounts of the more highly chlorinated PCBs should have improved environmental compatibility.


Plasma and erythrocyte zinc concentrations and their relationship to dietary zinc intake and zinc supplementation during pregnancy in low-income African-American women.
To evaluate the effects of usual dietary intake of zinc and of zinc supplementation during pregnancy on plasma and erythrocyte zinc concentrations. A randomized, double-blind, placebo-controlled trial. Low-income African-American women (n = 580) assigned randomly to groups at 19 weeks of gestation. A daily dose of zinc (25 mg) or a placebo until delivery. Plasma, erythrocyte, and dietary zinc levels. Multiple regression and repeated measures analysis of variance. In both the placebo and the supplemented groups, when all subjects were grouped by usual dietary zinc intake above or below the median (12 mg/day), results were the same: Women with high dietary zinc intake had higher erythrocyte zinc levels at the time of randomization and at all subsequent measurements during pregnancy than those who had low dietary zinc intake (P < or = .06; difference not significant for zinc-supplemented group); no difference was observed for plasma zinc levels. On the other hand, when the subjects were stratified at the median by total daily zinc intake (usual dietary zinc + 25 mg zinc supplement) during pregnancy, a significant difference in plasma zinc levels (P < .005) was found between women with high total zinc intake (mean = 38 mg/day) and low total intake (mean = 13 mg/day) at 26, 32, and 38 weeks of gestation; however, no such differences were found in erythrocyte zinc levels. These results should help dietitians and other health professionals better understand the expected changes in plasma and erythrocyte zinc levels during pregnancy, and the relationship between dietary and supplemental zinc and zinc nutriture.


Monitoring of unbound protein in vesicle suspensions with off-null ellipsometry.
In studies on the binding of proteins to small unilamellar phospholipid vesicles (SUV), the concentration of unbound protein usually remains unknown, because the vesicles cannot be separated from the bulk solution. In the present study, this limitation was overcome by addition of a supported planar phospholipid bilayer to the cuvette containing a vesicle suspension. Ellipsometric measurement of the protein adsorption velocities on this bilayer allowed determination of the concentrations of unbound protein. At high protein concentrations the adsorption is rapidly completed and the usual null-ellipsometry is too slow to obtain well-defined initial adsorption rates. Therefore, an off-null technique was developed, allowing measurement of the adsorbed protein mass at time intervals of 20 ms. Binding of prothrombin and coagulation factor Xa was measured in SUV suspensions prepared from a 20% dioleoylphosphatidylserine (DOPS) and 80% dioleoylphosphatidylcholine (DOPC) phospholipid mixture. For prothrombin, a dissociation constant Kd = 140 +/- 27 nM (mean +/- S.E.) and maximal surface concentration gamma max = (8.9 +/- 0.8) x 10(-3) mole of protein per mole of lipid, were obtained. For factor Xa, these values were Kd = 49.6 +/- 6.3 nM and gamma max = (23.0 +/- 1.4) x 10(-3) mole of protein per mole of lipid. These binding parameters are similar to those obtained earlier for planar bilayers. Apparently, the binding of factor Xa and prothrombin is not dependent on surface curvature.


Ectoine and hydroxyectoine inhibit aggregation and neurotoxicity of Alzheimer's beta-amyloid.
beta-Amyloid peptide (Abeta) is the major constituent of senile plaques, the key pathological feature of Alzheimer's disease. Abeta is physiologically produced as a soluble form, but aggregation of Abeta monomers into oligomers/fibrils causes neurotoxic change of the peptide. In nature, many microorganisms accumulate small molecule chaperones (SMCs) under stressful conditions to prevent the misfolding/denaturation of proteins and to maintain their stability. Hence, it is conceivable that SMCs such as ectoine and hydroxyectoine could be potential inhibitors against the aggregate formation of Alzheimer's Abeta, which has not been studied to date. The current work shows the effectiveness of ectoine and hydroxyectoine on the inhibition of Abeta42 aggregation and toxicity to human neuroblastoma cells. The characterization tools used for this study include thioflavin-T induced fluorescence, atomic force microscopy and cell viability assay. Considering that ectoine and hydroxyectoine are not toxic to cellular environment even at concentrations as high as 100 mM, the results may suggest a basis for the development of ectoines as potential inhibitors associated with neurodegenerative diseases.


Diagnostic power of relative sit-to-stand muscle power, grip strength, and gait speed for identifying a history of recurrent falls and fractures in older adults.
To compare the diagnostic value of relative sit-to-stand muscle power with grip strength or gait speed for identifying a history of recurrent falls and fractures in older adults. Data from an outpatient clinic included anthropometry (height/weight), bone density, 5 times sit-to-stand time (stopwatch and standardized chair), grip strength (hydraulic dynamometer), and gait speed (4 m). Relative sit-to-stand muscle power (W.kg-1, normalised to body mass) was calculated using a validated equation. Outcomes of falls (past 1 year) and fractures (past 5 years) were self-reported and verified by medical records wherever possible. Binary logistic regression considering for potential confounders (age, sex, BMI, Charlson comorbidity index, femoral neck bone density) and receiver operating characteristics (ROC) curves were used in statistical analysis. 508 community-dwelling older adults (median age: 78 years, interquartile range: 72, 83, 75.2% women) were included. Compared to greater relative sit-to-stand muscle power (1.62-3.78W.kg-1 for women; 2.03-3.90W.kg-1 for men), those with extremely low relative sit-to-stand muscle power were 2.35 (95% CI 1.54, 3.60, p < 0.001) and 2.41 (95% CI 1.25, 4.65, p = 0.009) times more likely to experience recurrent falls and fractures, respectively, in fully adjusted model. Compared to grip strength or gait speed, relative sit-to-stand muscle power showed the highest area under the ROC curve for identifying recurrent falls (AUC: 0.64) and fractures (AUC: 0.62). All tests showed low diagnostic power (AUC: < 0.7). Relative sit-to-stand muscle power performed slightly (but not statistically) better than grip strength or gait speed for identifying a history of recurrent falls and fractures in older adults. However, all tests showed low diagnostic power.


Preliminary results of robotic inguinal hernia repair following its introduction in a single-center trial.
Robotic surgery using the da Vinci system has markedly increased worldwide. However, robotic inguinal hernia repair remains unpopular outside the United States. We introduced and evaluated a robotic transabdominal preperitoneal repair (R-TAPP) technique for inguinal hernia in our hospital. First, we designed a task protocol according to the surgical results of 388 laparoscopic TAPP (L-TAPP) procedures performed during the 4 years prior to introducing R-TAPP. Our task protocol included several time limitations during a step-wise procedure: creating the peritoneal flap (<60 minutes), mesh placement with fixation (<30 minutes), and peritoneal suture closure (<30 minutes) under experienced supervision. We investigated the preliminary clinical results of R-TAPP performed by a single operator between December 2018 and January 2020. We identified 27 lesions in 20 patients (unilateral in 13 and bilateral in seven). According to the Japan Hernia Society Classification, our cohort included eight type I, five type II, and seven bilateral hernias (nine type I, four type II, and one type IV). The median operation time was 124 minutes (range, 81-164 minutes), and the median console operation time was 85 minutes (range, 50-132). The median time required for the peritoneal incision was 30 minutes (range, 18-54 minutes), that for mesh placement (including tucking) was 13 minutes (range, 7-27 minutes), and that for peritoneal suturing was 9 minutes (range, 3-20 minutes). Our preliminary results suggest that our task protocol for R-TAPP is feasible. However, refinement of our task protocol is essential for standardization.


Structures of mefenamic acid metabolites from human urine.
Three major metabolites of mefenamic acid were isolated from the urine of a normal adult man receiving mefenamic acid orally. The structures of those metabolites were determined as glucuronides of mefenamic acid, its hydroxymethyl derivative, and its carboxylic acid derivative on the basis of spectral data.


Measurement of Metabolites from Migrating Cells.
Metastasis is a multistep process that involves responses to extrinsic and intrinsic signals at every step. It is thus only truly appreciated in the context of a whole organism. Nevertheless, in vitro studies can be used to facilitate understanding of the possible factors contributing to any phenotype that is associated with metastatic competence. The use of migration assays-where monolayers of cells migrate to cover gaps or "wounds"-has been described for decades to identify signaling pathways that regulate motile competence and to screen for ways of interfering with this ability. Here we depict the combination of such an assay with assessment of indicators of carbon metabolism using commercially available assays. This enables identification of changes in cellular metabolism associated with actively migrating cells.


RNase E finds some sRNAs stimulating.
In this issue of Molecular Cell, Bandyra et al. (2012) describe how a bacterial sRNA can lead to degradation of an mRNA by pairing within the coding region of the mRNA; the 5' monophosphate end of the sRNA activates RNase E, leading to rapid cleavage of the paired mRNA.


Selective Benzylic CH-Borylations by Tandem Cobalt Catalysis.
Metal-catalyzed C-H activations are environmentally and economically attractive synthetic strategies for the construction of functional molecules as they obviate the need for pre-functionalized substrates and minimize waste generation. Great challenges reside in the control of selectivities, the utilization of unbiased hydrocarbons, and the operation of atom-economical dehydrocoupling mechanisms. An especially mild borylation of benzylic CH bonds was developed with the ligand-free pre-catalyst Co[N(SiMe3 )2 ]2 and the bench-stable and inexpensive borylation reagent B2 pin2 that produces H2 as the only by-product. A full set of kinetic, spectroscopic, and preparative mechanistic studies are indicative of a tandem catalysis mechanism of CH-borylation and dehydrocoupling via molecular CoI catalysts.


Time interval between onset of symptoms and COVID-19 testing in Brazilian state capitals, August 2020.
To analyze notifications of flu-like syndrome according to the time interval between onset of symptoms and testing for COVID-19. This was a cross-sectional study using records of flu-like syndrome cases containing results of COVID-19 diagnostic tests in the Brazilian state capitals and Federal District, held on the e-SUS Notifica system, from March 1st, 2020 to August 18th, 2020. The time interval between symptom onset and testing was compared using the ANOVA test, classifying it according to test adequacy/timeliness. Taking 1,942,514 notifications, average time between symptom onset and testing was 10.2 days (±17.1). Among those tested, females (55.1%), people aged 20-39 years (43.8%), and the Southeast region of Brazil (43.0%) predominated. 58.8% of IgM ELISA tests were performed at an adequate time while 68.0% of rapid antigen tests were not performed at an adequate time. Inadequacy was found between symptom onset and time taken to test for COVID-19 in the Brazilian regions.


Structural characterization of a fucoidan from Ascophyllum nodosum and comparison of its protective effect against cellular oxidative stress with its analogues.
In the present study, a fucoidan fraction (ANP-3) was isolated from Ascophyllum nodosum, and the combined application of desulfation, methylation, HPGPC, HPLC-MSn, FT-IR, GC-MS, NMR, and Congo red test elucidated ANP-3 (124.5 kDa) as a triple-helical sulfated polysaccharide constituted by →2)-α-Fucp3S-(1→, →3)-α-Fucp2S4S-(1→, →3,6)-β-Galp4S-(1→, →3,6)-β-Manp4S-(1→, →3,6)-β-Galp4S-(1→,→6)-β-Manp-(1→, →3)-β-Galp-(1→, α-Fucp-(1→, and α-GlcAp-(1→ residues. To better understand the relationship between the fucoidan structure of A. nodosum and protective effects against oxidative stress, two fractions ANP-6 and ANP-7 were used as contrast. ANP-6 (63.2 kDa) exhibited no protective effect against H2O2-induced oxidative stress. However, ANP-3 and ANP-7 with the same molecular weight of 124.5 kDa could protect against oxidative stress by down-regulating reactive oxygen species (ROS) and malondialdehyde (MDA) levels and up-regulating total antioxidant capability (T-AOC), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities. Then metabolites analysis indicated that arginine biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis metabolic pathways and metabolic biomarkers such as betaine were involved in the effects of ANP-3 and ANP-7. The better protective effect of ANP-7 compared to that of ANP-3 could be attributed to its relatively higher molecular weight, sulfate substitution and →6)-β-Galp-(1→ content, and lower uronic acid content.


Simultaneous determination of multi-residue and multi-class antibiotics in aquaculture shrimps by UPLC-MS/MS.
An accurate, reliable and fast multi-residue, multi-class method using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for simultaneous determination and quantification of 24 pharmacologically active substances of three different classes (Quinolones including fluoroquinolones, sulphonamides and tetracyclines) in aquaculture shrimps. Sample preparation involves extraction with acetonitrile containing 0.1% formic acid and followed by clean up with n-hexane and 0.1% methanol in water by UPLC-MS/MS within 8 min. The method was validated according to European Commission Decision 2002/657. Acceptable values were obtained for linearity (5-200 μg kg-1), specificity, Limit of Quantification (5-10 μg kg-1), recovery (between 83 and 100%), repeatability (RSD < 9%), within lab reproducibility (RSD < 15%), reproducibility (RSD ≤ 22%), decision limit (105-116 μg kg-1) and detection capability (110-132 μg kg-1). The validated method was applied to aquaculture shrimp samples from India.


Open controlled therapeutic trial of intravenous immune globulin in relapsing-remitting multiple sclerosis.
Ten patients with relapsing-remitting multiple sclerosis were treated with intravenous immune globulin, 0.4 g/kg per day for 5 consecutive days, and then with additional booster doses of immune globulin of 0.4 g/kg, once every 2 months, for the next 12 months. Ten untreated patients with relapsing-remitting multiple sclerosis who were matched with the study patients for age, disease duration, and number of attacks per year served as controls. Immune globulin treatment was well tolerated, with no side effects. The exacerbation rate decreased from 3.7 +/- 1.2 exacerbations per year before treatment to 1.0 +/- 0.7 exacerbations per year during the treatment in the immune globulin-treated patients, while it remained unaltered in the controls. The posttreatment Kurtzke Expanded Disability Status Scale score decreased from a mean of 4.45 to 4.15, whereas in controls it increased from 3.55 to 3.75. The results suggest that immune globulin suppresses the ongoing pathologic process in multiple sclerosis and may be a promising treatment to prevent disease exacerbations.


Livestock feed resources availability, feeding practices, and nutrient balances in high Himalaya (Gurez) valley of Kashmir.
Assessment of the ruminant livestock feed sources availability, existing feeding practices, and nutrient balances was embarked at different zones of Gurez valley of Kashmir in two major seasons (summer and winter). A baseline survey was conducted to obtain the information in three zones, viz., Lower, Middle and Upper Gurez. The study was carried out in three villages in each zone where seven farmer families per village were selected randomly for the study. A total of 63 households owning livestock were interviewed to collect the information and the samples of available animal feeds and fodders fed during the seasons for chemical analysis. Daily nutrient intakes were calculated and compared with the standard requirements to determine the nutrient balances of livestock during the seasons. The main crops cultivated only during summer season were pulses (98.41%), maize (95.24%), and potatoes (90.48%), while few farmers in Lower and Middle Gurez also sow oats (42.86%) and had apple orchards (17.46%), the by-products and wastes of which were utilized as livestock feeds. The only fodder crop cultivated throughout Gurez was maize. During winter, due to very harsh climatic conditions, no agricultural activities are being carried out, as such greenery perishes from the scenario. Feed resources availability to the livestock varied according to the season. Animals relied mainly on natural grazing resources available overabundant during summer and remained undernourished due to very limited feed resources during winter when completely stall-fed. Most of the farmers offered tree foliage (92%) and practiced concentrate feed (86%) supplementation to their animals particularly during winter season (96%). Farmers (87%) were preparing concentrate feed at home by blending ingredients available with them. Only 6% of the farmers supplemented the diet of animals with mineral mixture. Nutrient intakes through different feed resources were in excess during summer, while non-availability of green fodder during winter leads to considerable nutritional deficit in quantity, as well as quality. It is concluded that lack of technical know-how among the animal rearers regarding livestock feeding strategies and winter season feed/fodder scarcity are the major constraints that limit livestock productivity. It is therefore suggested that there is a dire need for nutritional innovations to increase fodder production as well as adoption of fodder conservation and feeding strategies for ensuring year-round availability of animal feeds if sustainable livestock production is to be met in the high Himalaya Gurez valley of Kashmir.


4-Meth-oxy-N'-(4-meth-oxy-benzyl-idene)benzohydrazide.
The title compound, C(16)H(16)N(2)O(3), was prepared by the reaction of 4-meth-oxy-benzaldehyde with 4-meth-oxy-benzohydrazide in methanol. The dihedral angle between the two benzene rings is 3.1 (3)°. In the crystal, inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into C(4) chains along the b axis.


A method for the interpretation of parasite egg counts in faeces of sheep.
A new method for the interpretation of strongyloid egg counts in faeces in sheep flocks is proposed. The "Flock Parasitism Index" (FPI) is based on three epizootiological concepts: extent of parasitism, distribution of its intensity, and risk of pasture contamination by eggs. In the estimation of FPI from a number of faecal samples from different animals in a flock, the percentage of parasitized sheep and the distribution of parasitized animals of the sample into the classical categories of "low", "moderate" and "high" from the number of eggs per gram of faeces (EPG) and the arithmetic mean of EPG of the sample are considered. The pathogenic and epizootiological importance of each one of the "low", "moderate" and "high" categories are considered to be 0.1, 0.5 and 1, respectively. From the relationship between EPG and worm burdens, probabilities for "low", "moderate" and "high" distributions are calculated, and from the percentages of worm burdens estimated and their levels of confidence at 95% it is suggested that values of FPI equal to 2.0 must be considered as the limit of parasitism where economic losses are tolerable.


Bronchopulmonary dysplasia and postnatal growth following extremely preterm birth.
To report the current incidence of bronchopulmonary dysplasia (BPD) and to compare changes in weight and head circumference between infants who developed BPD and infants who did not. Retrospective, whole-population study. All neonatal units in England between 2014 and 2018. All liveborn infants born <28 completed weeks of gestation. The change in weight z-score (ΔWz) was calculated by subtracting the birthweight z-score from the weight z-score at 36 weeks postmenstrual age (PMA) and at discharge. The change in head circumference z-score (ΔHz) was calculated by subtracting the birth head circumference z-score from the head circumference z-score at discharge. BPD was defined as the need for any respiratory support at 36 weeks PMA. 11 806 infants were included in the analysis. The incidence of BPD was 57.5%, and 18.9% of the infants died before 36 weeks PMA. The median (IQR) ΔWz from birth to 36 weeks PMA was significantly smaller in infants who developed BPD (-0.69 (-1.28 to -0.14), n=6105) than in those who did not develop BPD (-0.89 (-1.40 to -0.33), n=2390; adjusted p<0.001). The median (IQR) ΔHz from birth to discharge was significantly smaller in infants who developed BPD (-0.33 (-1.69 to 0.71)) than in those who did not develop BPD (-0.61 (-1.85 to 0.35); adjusted p<0.001). Postnatal growth was better in infants diagnosed with BPD compared with infants without BPD possibly due to more aggressive nutrition strategies.


Intracellular pyruvate-lactate-alanine cycling detected using real-time nuclear magnetic resonance spectroscopy of live cells and isolated mitochondria.
Pyruvate, an end product of glycolysis, is a master fuel for cellular energy. A portion of cytosolic pyruvate is transported into mitochondria, while the remaining portion is converted reversibly into lactate and alanine. It is suggested that cytosolic lactate and alanine are transported and metabolized inside mitochondria. However, such a mechanism continues to be a topic of intense debate and investigation. As a part of gaining insight into the metabolic fate of the cytosolic lactate and alanine; in this study, the metabolism of mouse skeletal myoblast cells (C2C12) and their isolated mitochondria was probed utilizing stable isotope-labeled forms of the three glycolysis products, viz. [3-13 C1 ]pyruvate, [3-13 C1 ]lactate, and [3-13 C1 ]alanine, as substrates. The uptake and metabolism of each substrate was monitored, separately, in real-time using 1 H-13 C 2D nuclear magnetic resonance (NMR) spectroscopy. The dynamic variation of the levels of the substrates and their metabolic products were quantitated as a function of time. The results demonstrate that all three substrates were transported into mitochondria, and each substrate was metabolized to form the other two metabolites, reversibly. These results provide direct evidence for intracellular pyruvate-lactate-alanine cycling, in which lactate and alanine produced by the cytosolic pyruvate are transported into mitochondria and converted back to pyruvate. Such a mechanism suggests a role for lactate and alanine to replenish mitochondrial pyruvate, the primary source for adenosine triphosphate (ATP) synthesis through oxidative phosphorylation and the electron transport chain. The results highlight the potential of real-time NMR spectroscopy for gaining new insights into cellular and subcellular functions.


Alternative treaty monitoring approaches using ultra-low background measurement technology.
The International Monitoring System (IMS) of the Comprehensive Test Ban Treaty includes a network of stations and laboratories for collection and analysis of radioactive aerosols. Alternative approaches to IMS operations are considered as a method of enhancing treaty verification. Ultra-low background (ULB) detection promises the possibility of improvements to IMS minimum detectable activities (MDAs) well below the current approach, requiring MDA < or = 30 microBq/m(3) of air for (140)Ba, or about 10(6) fissions per daily sample.


Prostacyclin, thromboxane A2 interactions in haemostasis and thrombosis.
Prostacyclin and thromboxane A2 are products of arachidonic acid which play a role in the regulation of haemostatic plug and thrombus formation. Aspirin inhibits the synthesis of both compounds but is more active in blocking TXA2 formation; based on this, aspirin is suggested to have an anti-thrombotic effect. Other possible approaches to the development of anti-thrombotic drugs are discussed.


Do type 2 diabetes patients without diabetic retinopathy or subjects with impaired fasting glucose have impaired colour vision? The Okubo Color Study Report.
To investigate associations between fasting plasma glucose level and the prevalence of acquired colour vision impairment in type 2 diabetes patients without diabetic retinopathy. Participants in this cross-sectional study of male officials aged 20-60 yr in the Japanese Self Defence Force, underwent colour vision testing, ophthalmic examination, a standardized interview and examination of venous blood samples. Ishihara plates, a Lanthony 15-hue desaturated panel and Standard Pseudoisochromatic Plates Part 2 were used to examine colour vision. The Farnsworth-Munsell 100-hue test was performed to define acquired colour vision impairment. Cardiovascular disease risk factors were determined from serum blood samples, physical records and an interview. We performed logistic regression analysis adjusted for age, diagnosed hypertension, dyslipidaemia, cataract, glaucoma, being overweight, smoking status and alcohol intake. Crude and adjusted odds ratios were calculated for three glucose levels, which included normal fasting glucose, impaired fasting glucose and diabetes. Out of a total of 1042 men enrolled, 872 were eligible for the study, and 31 were diagnosed with acquired colour vision impairment. As compared with the subjects with normal fasting glucose (< 5.6 mmol/l), the crude odds ratio for acquired colour vision impairment was 0.93 (95% CI 0.32-2.74) for the subjects with impaired fasting glucose (5.6-6.9 mmol/l) and 8.07 (95% CI 2.48-26.22) for the patients with type 2 diabetes. The multiple-adjusted odds ratios were 0.77 (95% CI 0.25-2.34) for the subjects with impaired fasting glucose and 5.89 (95% CI 1.55-22.40) for the patients with type 2 diabetes. Our findings suggest that there is a dramatically increased prevalence of acquired colour vision impairment in type 2 diabetes patients without diabetic retinopathy which might be attributable to another pathogenesis associated with diabetic retinopathy.


Tuberculin skin test. How to optimise?
The tests used in the diagnosis of tuberculosis latent infection, the tuberculin skin test (TST) and the interferon -gamma assays (IGRA), identify the existence of an adaptive immune response towards mycobacterial antigens. Considering the limitations of the two tests, the best solution is to take advantage of the best characteristics of each one. Most of the authors agree to the use of the two tests, using the IGRAS in the confirmation of a positive TST (because of its higher specificity). The operative characteristics of TST depend on the prevalence of the illness in the community and the aim of its use (its operative characteristics are higher when used in the tracing scope or as a diagnostic test). To interpret correctly a TST, the physician must know the epidemiology of tuberculosis in the community and correctly define the indications for its use.


Permanent extracorporeal esophagogastric tube for esophageal replacement.
Six patients are presented in whom an extracorporeal esophagogastric tube bypass was employed in lieu of standard methods of esophageal reconstruction. These tubes, obtained from Japan, have functioned well in 4 of the 6 patients. This approach offers an alternative to gastrostomy feedings alone in a patient with advanced esophageal disease in whom no other method of surgical reconstruction can be offered.


Lipid-dependent interaction of D-beta-hydroxybutyrate dehydrogenase with cellular membranes.
A mechanism of selective localization of membrane-bound enzymes was examined by studying the interaction between D-beta-hydroxybutyrate dehydrogenase (EC 184.108.40.206) and native cellular membranes in which the lipid components were altered. (1) The catalytic activity of the purified lipid-free enzyme could be restored by the re-interaction with microsomal and mitochondrial membranes, whereas with erythrocyte membranes or liposomes from lipids of erythrocyte membranes this activity could not be restored (Miyahara, M., Utsumi, K. and Deamer, D.W. (1981) Biochim. Biophys. Acta 641, 222-231). In the erythrocyte lipid components, only lysophosphatidylcholine markedly inhibited the enzyme reactivation. (2) The inhibitory effect of lysophosphatidylcholine was confirmed in microsomes in which the lysophosphatidylcholine contents had been increased, by phospholipase A2 treatment, to the levels in erythrocyte membranes. (3) Selective digestion by phospholipase C of phosphatidylcholine in the microsomes was accompanied by a lowering of the level of reactivation in the membranes. (4) The presence of lipophilic alkyl compounds such as cetylamine and cetyltrimethylammonium bromide, which contain the ammonium group, in the membranes also inhibited the enzyme reactivation. However, negatively charged and neutral alkyl compounds were less suppressive. The results above suggested that the interaction of D-beta-hydroxybutyrate dehydrogenase with native cellular membranes is dependent on the amounts of phosphatidylcholine and lysophosphatidylcholine exposed on the membrane surface. It was also suggested that the presence of the ammonium group of non-diacyl compounds is unfavorable for the effective interaction of the enzyme.


Cyanobacteria-/cyanotoxin-contaminations and eutrophication status before Wuxi drinking water crisis in Lake Taihu, China.
After the appalling "Wuxi Drinking Water Crisis", increasing investigations concerning the contaminations of cyanobacterial blooms and their toxins in Lake Taihu have been performed and reported in the last two years. However, information regarding these issues before the crisis in 2007 remained insufficient. To provide some background data for further comparisons, the present study reported our investigations conducted in 2004, associated with the cyanotoxin contaminations as well as the eutrophication status in Lake Taihu. Results from the one-year-study near a drinking water resource for Wuxi City indicated that, unlike the status in recent two years, cyanobacteria and chlorophyta are the co-dominance species throughout the year. The highest toxin concentration (34.2 ng/mL) in water columns occurred in August. In bloom biomass, the peak value of intracellular toxin (0.59 microg/mg DW) was determined in October, which was lag behind that in water column. In addition, MC-RR was the major toxin variant throughout the year. During the study period, nutrients levels of total nitrogen and phosphorus were also recorded monthly. Results from the present study will lead to a better understanding of the eutrophication status and the potential risks before "Wuxi Drinking Water Crisis".


Homoisoflavonoids from the bulbs of Bellevalia longipes and an assessment of their potential cytotoxic activity.
Seven undescribed homoisoflavonoids were identified from the bulbs of Bellevalia longipes Post (Asparagaceae) as well as thirteen known and one natural homoisoflavonoid that had been reported as a synthetic product previously. A general approach for recognizing homoisoflavonoids via NMR spectroscopy data were presented. The undescribed compounds were: 8-dehydroxy-5-O-demethyl-6-hydroxyscillapersicone, 6-methoxyscillapersicone, 5-O-demethyl-6-methoxyscillapersicone, 8-O-methylscillapersicone, 4'-O-methylscillapersicone, 4',8-O,O-dimethylscillapersicone, 3'-O-methylscillapersicone, and 3-hydroxy-desmethylophiopogonanone A. Structures were determined based on analysis of HRMS and NMR data, while absolute configurations were assigned using ECD spectroscopy. Human cancer cell lines were used to assess the cytotoxic activities of the isolated compounds, where 3-dehydroxy-3'-hydroxyeucomol showed IC50 values of 0.62 μM, 5.36 μM, and 2.52 μM, when tested against MDA-MB-435 (melanoma), MDA-MB-231 (breast), and OVCAR3 (ovarian) cells, respectively.


Role of the import motor in insertion of transmembrane segments by the mitochondrial TIM23 complex.
The TIM23 complex mediates translocation of proteins across, and their lateral insertion into, the mitochondrial inner membrane. Translocation of proteins requires both the membrane-embedded core of the complex and its ATP-dependent import motor. Insertion of some proteins, however, occurs in the absence of ATP, questioning the need for the import motor during lateral insertion. We show here that the import motor associates with laterally inserted proteins even when its ATPase activity is not required. Furthermore, our results suggest a role for the import motor in lateral insertion. Thus, the import motor is involved in ATP-dependent translocation and ATP-independent lateral insertion.


Spatial distribution, origin and contamination assessment of heavy metals in surface sediments from Jangsong tidal flat, Kangryong river estuary, DPR Korea.
This study aims to investigate spatial distribution, contamination and origin of heavy metals (Pb, Zn, Cu, Ni, Co and Cr) in surface sediments of Jangsong tidal flat (JTF), Kangryong river estuary, DPR Korea, where has been affected by various mining activities. The spatial diverse of heavy metals are due to differences in their sources and sediment properties. Enrichment factor, geoaccumulation index and ecological risk indexes indicate that JTF is not polluted and has low ecological risk, although slight enrichments occur for some metals. Multivariate analyses revealed that Mn, Ni and Cr originated from lithogenic source, whereas other metals were of anthropogenic origin, among which Fe and Co originated from the iron mine settling pond near JTF, while Pb, Zn and Cu originated from AMD effluent by sulfide mining activity in catchment of JTF. The different transport mechanisms of heavy metals from AMD result in diverse distribution of the metals in JTF.


Perspectives on methodology for in vitro culture of Helicobacter pylori.
Over the past 25 years, a variety of methods have been developed for culture of Helicobacter pylori in vitro. H. pylori is a capnophilic and microaerophilic organism that is typically cultured using complex culture media. Analysis of H. pylori growth in chemically defined media has provided insight into the nutritional requirements, physiology, and metabolic capacities of this organism.


Insights in Hodgkin Lymphoma angiogenesis.
Angiogenesis is a hallmark of tumor growth and progression in solid and hematological malignancies. Different cellular components of the tumor microenvironment such as macrophages, mast cells, circulating endothelial cells and angiogenic factors, including vascular endothelial growth factor and its receptors are involved in the maintenance of Hodgkin Lymphoma. In this review article, we highlight relevant literature focusing on the relationships between angiogenesis and Hodgkin Lymphoma as well as discussing anti-angiogenic treatments in this malignancy.


The elevation of cyclic GMP as a response to acute hypervolemia is blocked by a monoclonal antibody directed against atrial natriuretic peptides.
Substantial volume expansion in conscious rats induces a strong diuresis and natriuresis that is caused by the increase in plasma levels of atrial natriuretic peptides (ANP) as measured by a radioimmunoassay. This renal response could be blocked by monoclonal antibodies directed against ANP. Parallel to the change in ANP, the cyclic GMP levels in plasma, urine and kidney tissue were increased after volume loading and reduced after additionally given antibodies. From this study it seems to be clear that the cyclic GMP rise is not a direct effect of volume expansion but is specifically mediated by the released ANP.


Sensitive detection of sulfide ions in red region based on luminescence resonance energy transfer between upconversion nanoparticles and dye-670.
Many sulfides are toxic substances that easily harm the respiratory tract, therefore affecting respiratory function or damaging other organs of the body, leading to its failure. Therefore, there is a pressing need to develop methods for sensitive detection of sulfur ions (S2- ). Based on luminescence resonance energy transfer (LRET) theory, we report the construction of a near-infrared (NIR) excitation luminescence probe using NaGdF4 :Yb3+ ,Er3+ @NaYF4 upconversion nanoparticles (UCNPs) as the donor and dye-670 as the receptor for detection of S2- . When UCNPs and dye-670 molecules were combined using ligand exchange and electrostatic attraction, LRET occurred and UCNP luminescence was quenched. When S2- was added to the system, sulfide ions were able to destroy the double bond of the dye, inhibiting LRET and restoring UCNP luminescence. Under optimum condition, the linear range of S2- detection was 0.65-18.2 μM, and the detection limit was 34.2 nM. This method was applied for determination of S2- in water with satisfactory results.


Visual information of vehicle velocity acquired by pedestrians involved in road crossing accidents.
This paper describes a geometric optical relationship between the perceived visual information of approaching vehicles by pedestrians who intend to cross the road and the factors underlying pedestrian accidents in Japan. We create a model based on this visual information, wherein the retinal image corresponding to vehicle velocity perception is broken down into tangential components and normal components in a two-dimensional polar coordinate system that employs the nodal point of the eyeball as the origin. Our visual model uses the relationship between the tangential and normal components of the velocity to calculate the distance at which the velocity of the vehicle can be perceived by pedestrians. The maximum distance at which vehicle velocity can be perceived by pedestrians derived from the visual model is consistent with the timing at which a vehicle collides with a pedestrian most frequently in the pedestrian accidents gleaned from accident statistics. The result of the simulation of the visual model showed that the eye height of the pedestrian, the total height of the vehicle and the sensory threshold of motion determine the components by which the maximum perception distance of the vehicle velocity is given. These findings contribute to the enhancement of safety measures in traffic accidents from the pedestrian's perspective.


Therapeutic time window for the application of chondroitinase ABC after spinal cord injury.
Rats with a crush in the dorsal funiculi of the C4 segment of the spinal cord were treated with chondroitinase ABC delivered to the lateral ventricle, receiving 6 intraventricular injections on alternate days. In order to investigate the time window of efficacy of chondroitinase, treatment was begun at the time of injury or after a 2, 4 or 7 days delay. Behavioural testing over 6 weeks showed that acutely treated animals showed improved skilled forelimb reaching compared to penicillinase controls. Forelimb contact placing recovered in treated animals but not controls, and gait analysis showed recovery towards normal forelimb stride length in treated animals but not controls. Chondroitinase-treated animals showed greater axon regeneration than controls. The treatment effect on contact placing, stride length and axon regeneration was not dependent on the timing of the start of treatment, but in skilled paw reaching acutely treated animals recovered better function. The area of chondroitinase ABC digestion visualized by stub antibody staining included widespread digestion around the lateral ventricles and partial digestion of cervical spinal cord white matter, but not grey matter.


MRI appearances of borderline ovarian tumours.
This review was performed to describe the range of magnetic resonance imaging (MRI) appearances of borderline ovarian tumours. The MRI findings in 26 patients with 31 borderline ovarian tumours (mean age: 40.1 years, range: 14-85 years) were retrospectively reviewed. For each tumour, site, size, MRI characteristics, and enhancement following gadolinium administration were recorded. There were 20 serous and 11 mucinous borderline ovarian subtypes. Nine of 26 patients demonstrated bilateral disease on MRI; synchronous contralateral ovarian disease included three benign, five serous borderline, and one serous invasive tumour. A history of a metachronous mucinous borderline tumour was identified in one patient. MRI appearances were classified into four morphological categories: group 1 (6/31, 19%), unilocular cysts; group 2 (6/31, 19%), minimally septate cysts with papillary projections; group 3 (14/31, 45%), markedly septate lesions with plaque-like excrescences; and group 4 (5/31, 16%), predominantly solid with exophytic papillary projections, all of serous subtype. There was a significant difference in mean volume between serous (841.5 cm(3)) and mucinous (6358.2 cm(3)) subtypes (p=0.009). All tumours demonstrated at least one MRI feature suggestive of malignancy. The present review demonstrates the variable MRI appearances of borderline ovarian tumours along with imaging features suggestive of tumour subtype. In patients in whom the clinical features are suggestive of a borderline ovarian tumour (young age and normal or minimally elevated CA125), the ability to predict a borderline disease using morphological features observed on MRI would be extremely helpful in surgical planning, with the potential to offer fertility or ovary-preserving surgery. Future studies are required to further this aim.


Optical coherence tomography, intravascular ultrasound or angiography guidance for distal left main coronary stenting. The ROCK cohort II study.
to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid-term outcome accordingly. Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited. ROCK II is a multicenter, investigator-driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal-LM stenting. The primary study endpoint was target-lesion failure (TLF) including cardiac death, target-vessel myocardial infarction and target-lesion revascularization. We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non-inferiority of OCT versus IVUS. A total of 730 patients, 377 with intravascular-imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one-year rate of TLF was 21.2% with angiography and 12.7% with intravascular-imaging (p = 0.039), with no difference between OCT and IVUS (p = 0.26). Intravascular-imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23-0.93: p = 0.03). Propensity-score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one-year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p = 0.03 for IVUS or OCT vs. angiography). No between-group significant differences in the rate of individual components of TLF were found. Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS.


A genetic analysis of stereotypy in the mouse: dopaminergic plasticity following chronic stress.
After repeated stressful experiences, DBA/2 (DBA) mice showed an increase in apomorphine-induced climbing while C57BL/6 (C57) mice showed a clear-cut decrease of this behavior. Genetic analysis involving F1 and F2 hybrids and the backcross populations (F1 X C57; F1 X DBA) indicated complete dominance of the C57 genotype and a significant genotype X environment interaction. These findings are discussed in terms of dopaminergic plasticity and of the heuristic value of this animal model in relation to disturbed behaviors triggered by stressful experiences.


Diagnosis of Active Pulmonary Tuberculosis and Community Acquired Pneumonia Using Convolution Neural Network Based on Transfer Learning.
A convolutional neural network (CNN) model for the diagnosis of active pulmonary tuberculosis (APTB) and community-acquired pneumonia (CAP) using chest radiographs (CRs) was constructed and verified based on transfer learning. CRs of 1247 APTB cases, 1488 CAP cases and 1247 normal cases were collected. All CRs were randomly divided into training set (1992 cases), validation set (1194 cases) and test set (796 cases) by stratified sampling in 5:3:2 radio. After normalization of CRs, the convolution base of pre-trained CNN (VGG16) model on ImageNet dataset was used to extract features, and the grid search was used to determine the optimal classifier module, which was added to the convolution base for transfer learning. After the training, the model with the highest accuracy of the validation set was selected as the optimal model to verify in the test set and calculate the accuracy of the model. The accuracy of validation set in the 63rd epochs was the highest, which was 0.9430, and the corresponding Categorical crossentropy was 0.1742. The accuracy of the training set was 0.9428, and the Categorical crossentropy was 0.1545. When the optimal model was applied to the test set, the accuracy was 0.9447, and the Categorical crossentropy was 0.1929. The transfer learning-based CNN model has good classification performance in the diagnosis of APTB, CAP and normal patients using CRs.


Establishment of Guidelines for the Control of Glycosylation Reactions and Intermediates by Quantitative Assessment of Reactivity.
Stereocontrolled chemical glycosylation remains a major challenge despite vast efforts reported over many decades and so far still mainly relies on trial and error. Now it is shown that the relative reactivity value (RRV) of thioglycosides is an indicator for revealing stereoselectivities according to four types of acceptors. Mechanistic studies show that the reaction is dominated by two distinct intermediates: glycosyl triflates and glycosyl halides from N-halosuccinimide (NXS)/TfOH. The formation of glycosyl halide is highly correlated with the production of α-glycoside. These findings enable glycosylation reactions to be foreseen by using RRVs as an α/β-selectivity indicator and guidelines and rules to be developed for stereocontrolled glycosylation.


Characteristics of the immediate postarthroscopic blood clot formation in the knee joint.
The immediate postoperative bleeding and blood clot formation was observed in 26 human knee joints following a variety of arthroscopic surgical procedures. Observations were made following lavage with lactated Ringer's and normal saline solutions. Bleeding occurred from all incised vascular tissue. Blood clot accumulated after each solution within 5 min following tourniquet release and decompression of the joint. Most of the blood clot remained unattached within the joint cavity. Blood clot did attach to all surgically incised or excised surfaces. The clinical relevance of these observations is related to the potential role of the blood clot in intraarticular tissue repair following arthroscopic surgery.


Local antifertility effect of luteinizing hormone-releasing hormone (LRH).
Injection of luteinizing hormone-releasing hormone (LRH) into the right uterine horn of the rat on D5 produced a dose related inhibition of pregnancy in the treated horn. The number of viable fetuses as well as the uterine weight was reduced while the number of placental sites was increased. The contralateral uninjected horn was unaffected. These data demonstrate that LRH can inhibit pregnancy in the rat through an extrapituitary effect.


RETRACTED: MZF1 regulates α-globin gene transcription via long-range interactions in erythroid differentiation.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). The article has been retracted at the request of the editor. The journal was informed by Dr Xiangmin Xu and Dr Yongzhong Zhao that they were not involved in the study or research and that the article was submitted without their knowledge. As such this article represents a misuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process. All authors were informed of the article retraction however Dr Li and Dr Zeng did not respond to the enquiries.


Type XI collagen is associated with the chondrocyte surface in suspension culture.
Chondrocytes from bovine articular cartilage were stripped of matrix, then allowed to reconstitute their pericellular matrix in suspension culture. After incubation, the cells were centrifuged through a Percoll (TM) cushion and separated into a cell fraction, a medium fraction, and an interface fraction. The collagen in each fraction was analyzed by SDS-polyacrylamide gel electrophoresis and immunolocation with antisera against type XI and type II. Under these conditions, type XI collagen was recovered in the cell fraction, but was not detectable by immunolocation in the medium fraction or the interface fraction. In contrast, type II collagen was found in all three of these fractions. Insoluble type XI fibers subjected to the same fractionation scheme in the absence of cells were recovered in the medium and interface fractions, but not in the cell fraction. Incubation of intact cells with collagenase digested the cell-associated collagen, indicating that it was outside of the cells. The type XI collagen was removed from the cells by extraction with 4 M guanidinium chloride. These results indicate that type XI collagen is preferentially retained at the chondrocyte surface, and are consistent with our proposal that it is involved in organization of the pericellular matrix.


First next-generation sequencing data for Haploporidae (Digenea: Haploporata): characterization of complete mitochondrial genome and ribosomal operon for Parasaccocoelium mugili Zhukov, 1971.
The first data on a whole mitochondrial genome of Haploporidae, Parasaccocoelium mugili (Digenea: Haploporata: Haploporidae) was generated using the next-generation sequencing (NGS) approach. We sequenced the complete mitochondrial DNA (mtDNA) and ribosomal operon of Parasaccocoelium mugili, intestine parasite of mullet fish. The mtDNA of P. mugili contained 14,021 bp, including 12 protein-coding genes, two ribosomal genes, 22 tRNA genes, and non-coding region. The ribosomal operon of P. mugili was 8308 bp in length, including 18S rRNA gene (1981 bp), ITS1 rDNA (955 bp), 5.8S rRNA gene (157 bp), ITS2 rDNA (268 bp), 28S rRNA gene (4180 bp), and ETS (767 bp). We used the mtDNA protein-coding regions to make phylogenetic reconstructions of Haploporidae. Additionally, we performed the sequence cluster analysis based on codon usage bias of most of currently available mitochondrial genome data for trematodes. The observed gene arrangement in mtDNA sequence of P. mugili is identical to those of Plagiorchis maculosus (Rudolphi, 1802). Results of maximum likelihood (ML) phylogenetic analysis showed that P. mugili was closely related to Paragonimus species from the suborder Xiphidiata. The results of sequence cluster analysis based on codon usage bias showed that P. mugili has the highest similarity with Plagiorchis maculosus (Xiphidiata). Our results do not contradict to proposing a new suborder for Haploporoidea-Haploporata. On the basis of obtained results, the relationship between mitochondrial protein-coding gene rearrangements and synonymous nucleotide substitutions in mitochondrial genomes has been suggested.


[Treatment of subacute cutaneous lupus erythematosus with thalidomide].
A patient with subacute-cutaneous lupus erythematosus showed no response to corticosteroids and azathioprine. Treatment with thalidomide resulted in a dramatic clearing of skin lesions but failed to improve pathological laboratory tests.


Sublethal effects of pesticide mixtures on selected biomarkers of Carassius auratus.
In the present study, the in vivo effects of commercial propoxur alone and in combination with isoprocarb and chlorpyrifos on acetylcholinesterase and glutathione S-transferases activities in goldfish (Carassius auratus) were investigated. Brain and muscle AChE activity was significantly inhibited (88% and 85% at most, respectively) by propoxur after 5 d of exposure at concentrations between 141 and 2263μg/L, bell-shaped concentration-response curves were obtained. In most cases, time dependence was apparent. Under insecticide mixture exposure (binary mixture propoxur/isoprocarb and ternary mixture propoxur/isoprocarb/chlorpyrifos), the inhibition of AChE activity was significant in all cases and linear concentration-response relationships were observed. Propoxur (alone and in combination) significantly inhibited gill GST activity, and both mixtures also induced significant inhibition of liver GST activity. However, concentration and time dependence were not apparent. AChE is likely to be more informative than GST and seems to be a good biomarker to diagnose exposure to anticholinesterase pesticides in wild populations of this species.