Electron microscopic mapping of single-stranded discontinuities in cauliflower mosaic virus DNA by means of the biotin-avidin technique.
Biotin-labeled deoxyuridine triphosphate has been used to label the three natural single-stranded discontinuities of Cauliflower Mosaic Virus DNA. The presence of biotin permitted the direct visualization and mapping of the discontinuities by electron microscopy, using ferritin-labeled avidin.


[Resistance Mechanisms to Immune Checkpoint Inhibitor and Its Overcome with Focus on β-Catenin in Lung Cancer].
Although the indications for immune checkpoint inhibitors are expanding rapidly, the disease will eventually progress in many patients. Elucidating and overcoming the resistant mechanisms to immune checkpoint inhibitors is a major challenge. WNT/β-catenin pathway has long been known as one of the mechanisms involved in cell proliferation and epithelial-mesenchymal transition in cancer development. Recently, it has become clear that WNT/β-catenin pathway also plays a role in cancer immune escape, as reported in melanoma. We have also studied WNT/β-catenin pathway as a mechanism of immune escape in lung cancer. In this article, we review how WNT/β-catenin pathway is involved in immune escape and resistance to immune checkpoint inhibitors, mainly in non-small cell lung cancer. In addition, we discuss how to overcome the tumor immune mechanism caused by WNT/β-catenin pathway in the context of current combination therapies and therapies in development.


Non-invasive in vivo monitoring of transplanted stem cells in 3D-bioprinted constructs using near-infrared fluorescent imaging.
Cell-based tissue engineering strategies have been widely established. However, the contributions of the transplanted cells within the tissue-engineered scaffolds to the process of tissue regeneration remain poorly understood. Near-infrared (NIR) fluorescence imaging systems have great potential to non-invasively monitor the transplanted cell-based tissue constructs. In this study, labeling mesenchymal stem cells (MSCs) using a lipophilic pentamethine indocyanine (CTNF127, emission at 700 nm) as a NIR fluorophore was optimized, and the CTNF127-labeled MSCs (NIR-MSCs) were printed embedding in gelatin methacryloyl bioink. The NIR-MSCs-loaded bioink showed excellent printability. In addition, NIR-MSCs in the 3D constructs showed high cell viability and signal stability for an extended period in vitro. Finally, we were able to non-invasively monitor the NIR-MSCs in constructs after implantation in a rat calvarial bone defect model, and the transplanted cells contributed to tissue formation without specific staining. This NIR-based imaging system for non-invasive cell monitoring in vivo could play an active role in validating the cell fate in cell-based tissue engineering applications.


High-throughput enrichment and isolation of megakaryocyte progenitor cells from the mouse bone marrow.
Megakaryocytes are a rare population of cells that develop in the bone marrow and function to produce platelets that circulate throughout the body and form clots to stop or prevent bleeding. A major challenge in studying megakaryocyte development, and the diseases that arise from their dysfunction, is the identification, classification, and enrichment of megakaryocyte progenitor cells that are produced during hematopoiesis. Here, we present a high throughput strategy for identifying and isolating megakaryocytes and their progenitor cells from a heterogeneous population of bone marrow samples. Specifically, we couple thrombopoietin (TPO) induction, image flow cytometry, and principal component analysis (PCA) to identify and enrich for megakaryocyte progenitor cells that are capable of self-renewal and directly differentiating into mature megakaryocytes. This enrichment strategy distinguishes megakaryocyte progenitors from other lineage-committed cells in a high throughput manner. Furthermore, by using image flow cytometry with PCA, we have identified a combination of markers and characteristics that can be used to isolate megakaryocyte progenitor cells using standard flow cytometry methods. Altogether, these techniques enable the high throughput enrichment and isolation of cells in the megakaryocyte lineage and have the potential to enable rapid disease identification and diagnoses ahead of severe disease progression.


Cognitive enhancement therapy for a model of Down syndrome.
Down syndrome is a complex condition that results from having a third copy of human chromosome 21. People with the syndrome experience problems with learning and memory that affect many aspects of their lives. In this issue of Science Translational Medicine, Salehi et al. report on successful drug treatment of learning deficits in an animal model of Down syndrome. This study highlights the function of the norepinephrine-ergic system in Down syndrome and suggests possible treatment options for people with Down syndrome.


Aerobic fitness is associated with lower proportions of senescent blood T-cells in man.
Senescent T-cells accumulate with age, lowering the naïve T-cell repertoire and increasing host infection risk. As this response is likely to be influenced by certain lifestyle factors, we examined the association between aerobic fitness (VO(2max)) and the age-related accumulation of senescent T-cells. Blood lymphocytes from 102 healthy males (18-61 yr) were analyzed for KLRG1, CD57, CD28, CD45RA, CD45RO surface expression on CD4+ and CD8+ T-cells by 4-color flow cytometry. Advancing age (yr) was positively associated with the proportion (%) of senescent (KLRG1+/CD57+; KLRG1+/CD28-) CD4+ (B=1.00; 1.02) and CD8+ (B=0.429; 1.02) T-cells and inversely associated with naïve (KLRG1-/CD28+) CD4+ (B=-1.000) and CD8+ (B=-0.993) T-cells. VO(2max) was inversely associated with senescent CD4+ (B=-0.97) and CD8+ (B=-0.240). Strikingly, age was no longer associated with the proportions of senescent or naïve T-cells after adjusting for VO(2max), while the association between VO(2max) and these T-cell subsets withstood adjustment for age, BMI and percentage body fat. Ranking participants by age-adjusted VO(2max) revealed that the highest tertile had 17% more naïve CD8+ T-cells and 57% and 37% less senescent CD4+ and CD8+ T-cells, respectively, compared to the lowest tertile. VO(2max) was not associated with latent cytomegalovirus (CMV), Epstein-Barr virus (EBV) or herpes simplex virus-1 (HSV-1) infection, indicating that the moderating associations of VO(2max) were not confounded by persistent viral infections. This is the first study to show that aerobic fitness is associated with a lower age-related accumulation of senescent T-cells, highlighting the beneficial effects of maintaining a physically active lifestyle on the aging immune system.


Atypical manifestation of a fistula between a hydatid cyst of a liver and a gallbladder: A case report.
The hydatid cyst of the liver is the most common location of hydatid disease. Complications in this form are dominated by superinfection of the cyst and rupture into the bile ducts or the peritoneal cavity. We report the case of a 54-year-old female patient with a hydatid cyst of the liver complicated by a rupture in the gallbladder revealed by urinary symptoms.


Analysis of the subsequent treatment of osteoporosis by transitioning from bisphosphonates to denosumab, using quantitative computed tomography: A prospective cohort study.
Denosumab reduces bone resorption and improves bone mineral density (BMD). Studies have analyzed subsequent treatment transitioning from bisphosphonates to denosumab based on dual-energy X-ray absorptiometry scanning (DXA). Quantitative computed tomography (QCT) can help assess cortical and trabecular bones separately in three dimensions without the interference of the surrounding osteophytes. In the present study, we analyzed the subsequent treatment transition from bisphosphonates to denosumab using QCT. Thirty-two patients with postmenopausal osteoporosis to be treated with denosumab were recruited. The patients were divided into two groups (15 prior bisphosphonate and 17 naïve) based on their previous treatment. BMD of the lumbar spine and hip were evaluated by DXA and QCT at baseline and 12 months following denosumab treatment. The percentage change in volumetric BMD assessed by QCT at 12 months significantly improved in the naïve group compared with that in the prior bisphosphonate group. The region-specific assessment of femur at 12 months revealed that denosumab treatment was effective in both cortical and trabecular bones except the trabecular region of the prior bisphosphonate group. Our study suggests that although denosumab treatment was useful in both treatment groups, BMD increase was significantly higher in the naïve group than in the prior-bisphosphonate group. Interestingly, in the prior-bisphosphonate group, denosumab treatment was more effective in the cortical region than the trabecular region. Our study offers insights into the subsequent treatment and permits greater confidence when switching to denosumab from bisphosphonates.


An outlet obstruction caused by V-shaped bar at the bladder neck in a woman.
A case of outlet obstruction caused by a V-shaped bar at the bladder neck in a woman was treated successfully by transurethral resection of the bar. The poor urinary flow in our patient was believed to be due to impedance during voiding caused by retraction of the bladder neck in the anteroposterior direction by the bar. Our case is different from previously reported cases.


Are UK commercial expeditions complying with wilderness medical society guidelines on ascent rates to altitude?
The incidence of acute mountain sickness can be reduced by ascending slowly to altitude. We compared a recommended ascent rate with those offered by commercial companies to three of the most popular high-altitude destinations in the world. While the majority complied with the recommended ascent rate, ascents on Kilimanjaro did not.


America in the 1980s: 10 major changes ahead.
At least 10 major developments will substantially change our country, our lives, our livelihoods, and our families in the 1980s. Despite all of our immediate and visible problems, if we Americans follow sensible policies of government deregulation, of capital formation, of energy conservation, and energy development, then the economic, the political, and the social future of the United States in the revolutionary 1980s is absolutely dazzling.


The role of substance use in the lives of incarcerated older adults: A qualitative study.
The prevalence of drug abuse among older adults has grown over the last decade. Despite the expanding development of a body of research dedicated to studying this phenomenon, drug abuse by incarcerated older adults has been marginalized. Thus, the aim of the present study was to explore drug abuse patterns in the lives of incarcerated older adults. Semi-structured interviews were conducted with 28 incarcerated older adults, and an interpretive analysis was used to analyze the participants' narratives. Four themes emerged: (1) Growing up around drugs; (2) Prison onset; (3) Professionals, and (4) Lifelong substance abuse. The study findings reveal a unique typology of drug-related themes in the lives of incarcerated older adults. This typology sheds light on the interplay between aging, drug use, and incarceration and the way these three socially marginalized positions may intersect.


In vivo proof of concept of oral insulin delivery based on a co-administration strategy with the cell-penetrating peptide penetratin.
Oral delivery of insulin is blocked by low intestinal absorption caused by the poor permeability of insulin across cellular membranes and the susceptibility to enzymatic degradation in the gastrointestinal tract. Cell-penetrating peptides (CPPs) have been investigated for a number of years as oral absorption enhancers for hydrophilic macromolecules. Penetratin, a cationic and amphipathic CPP, effectively enhances insulin absorption and we were able to alleviate the enzymatic barrier by using the enzymatic resistant D-form of penetratin. In this study, mice were dosed orally with a physical mixture of insulin and penetratin. Blood glucose concentrations were measured and a pharmacological availability (PA) of 18.2% was achieved in mice dosed with insulin and D-penetratin. Following the promising data, we investigated the degradation parameters of insulin and penetratin in rat intestinal fluid. As expected, L-penetratin was degraded rapidly whereas D-penetratin had a halflife of 67±7min in 10-fold diluted gastrointestinal fluid. Insulin degradation was slowed by the presence of penetratin in intestinal fluid. The half-life of insulin increased from 24.9±4.5min to 55.6±14min and 90.5±11.8min in the presence of L- and D-penetratin respectively. In conclusion, both Land D-penetratin acted as oral absorption enhancers at select CPP concentrations for insulin and the current study is the first solid evidence of pharmacological activity of oral insulin delivery systems based on non-covalent intermolecular interactions with penetratin.


Insurance disparity in cardiovascular mortality among non-elderly cancer survivors.
Insurance status plays a vital role in cancer diagnosis, treatments and survival. Cancer patients have higher cardiovascular disease (CVD) mortality than the general population. The Surveillance, Epidemiology and End Results (SEER) program 2007-2016 was used to estimate the CVD mortality among cancer patients aged 18 to 64 years at the time of diagnosis of an initial malignancy with the eight most prevalent cancers. Standardized mortality ratios (SMRs) were calculated for each insurance (Non-Medicaid vs Medicaid vs Uninsured) using coded cause of death from CVD with adjustment of age, race, and gender. The Fine-Grey Model was used to estimate adjusted Hazard Ratios (HR) of each insurance in CVD mortality. A total of 768,055 patients were included in the final analysis. CVD death in patients with Medicaid insurance remained higher than in those with Non-Medicaid insurance (HR = 1.71; 95%CI, 1.61-1.81; p < 0.001). Older age, male gender, and black race were all associated with increased CVD mortality in the multivariable model. Compared to the general population, patients with Medicaid had the highest SMRs of CVD mortality, regardless of year of cancer diagnosis, follow-up time, cancer site, and race. Non-Medicaid insured patients had similar CVD mortality to the general population after 2 years out from their cancer diagnosis. Cancer patients with Non-Medicaid insurance have significantly lower CVD mortality than those with no insurance or Medicaid. The insurance disparity remained significant regardless of type of CVD, cancer site, year of diagnosis and follow-up time.


Therapeutic sectorial full-thickness sclero-keratoplasty for recurrent fungal keratitis.
To report the management of a severe and recurrent fungal keratitis that required repeated penetrating keratoplasties. Despite multiple topical, intraocular and systemic antifungal treatments, superotemporal hyphal infiltration repeatedly penetrated the corneal transplant causing continuous recurrences. Cultures collected before and during surgery isolated the same organism, Fusarium spp. Corneal infection extending to the sclera and internal angle structures is the main cause of recurrence of fungal keratitis after corneal transplantation. Sectorial full-thickness sclero-keratoplasty combined with a central penetrating keratoplasty should be a surgical technique to be considered in cases where these locations are suspected to be the source of recurrence. It enables a definitive elimination of the infection, with excellent final visual acuities. No postoperative complications were reported in this case.


Ageing in people with autistic spectrum disorder.
Although autism in children and in adults attracts attention with respect to clinical and research needs, autism in the older individuals has not been considered to any degree. We review the evidence for urgently addressing the question of ageing in people with autistic spectrum disorder (ASD), focusing on those with disability. Perspectives are reviewed in relation to demographics, experiences of relatives or carers, anticipated residential care needs, requirement for specifically designed cognitive assessment tools and importance of initiating new brain ageing research initiatives in this area. With escalating numbers of ASD individuals with disability reaching old age, provision of care is the paramount issue that is only beginning to be addressed in a few European communities and in the USA. How ageing affects cognition in such individuals as they reach an age no longer consistent with parental care is unknown, lacking any published evidence, and there is a clear need to design cognitive and behavioural assessment tools appropriate to ageing in ASD individuals with disability, as was the case with respect to dementia as a whole. Although there is a growing body of evidence on pathological, imaging, neuropharmacological and other key brain abnormalities in ASD, these are, to date, confined to children and young (only rarely to middle aged) adults. The need for new initiatives in research into ageing in ASD is urgent. Apart from a growing care crisis, the prospect of understanding brain ageing in this population may bring potential rewards beyond immediate clinical need given the precedent of Down syndrome.


My Space, Your Space, Our Space: Exploring the Potential of Collaborative Group Facilitation Between Therapists and Peer Workers in Mental Health Settings.
This paper explores the potential of collaborative group facilitation between therapists and peer workers in mental health. A case study of co-practice between a music therapist and a peer worker is used to illustrate how lived experience expertise can enrich and complement therapeutic groups. The paper aims to begin a discussion around collaborative group facilitation within mental health practice and to advocate for continued development of collaborative practice between peer workers and therapists. Experiences of collaboration are explored through the case study provided using a synthesis of the authors' reflections and dialogue. The importance of role negotiation, role definition, and open communication around changing roles and boundaries are discussed as key considerations for beginning collaborations, as well as the establishment and maintenance of a foundation of trust and support within the working relationship.


Cognitive impairment, childhood trauma, sedentary behaviour, and elevated C-reactive protein levels in major affective disorders.
Elevated C-reactive protein (CRP) levels were associated with cognitive decline, sedentary behaviour, and childhood trauma in patients with major affective disorders. This study aims to examine the association of peripheral CRP levels, cognitive function, childhood trauma, sedentary behaviour, and quality of life in individuals with major affective disorders, including bipolar disorder (BD), major depressive disorder (MDD), and individuals without mood disorders (controls). We included outpatients with BD (n = 42), MDD (n = 27), and healthy controls (n = 40). All participants were assessed by a questionnaire, structured clinical interview, and the following scales: international physical activity questionnaire, childhood trauma questionnaire, 17-item Hamilton Depression Rating Scale (HDRS17), and World Health Organization Quality of Life instrument, brief version (WHOQOL-BREF). Other measures were included: hs-CRP levels, anthropometric measures, and cognitive tests (Trail-making test part A and part B, Stroop test, phonemic verbal fluency test, and semantic verbal fluency test). Our results indicated that BD outpatients were less significantly physically active on leisure domain than controls. Levels of hs-CRP ≥ 5 mg/L were significantly linked with a history of childhood sexual abuse and childhood physical abuse, as well as worse neurocognitive performance in major depressive disorders, mainly in BD. There was a significant negative correlation between Trail-making part B score and WHOQOL-BREF total score. The findings support the hypothesis that levels of hs-CRP ≥ 5 mg/L may be a possible predictor of cognitive dysfunction, childhood sexual abuse and sedentary behaviour in major affective disorders.


Phylogenetic analysis of macroecological patterns of home range area in snakes.
A home range is the area animals use to carry out routine activities such as mating, foraging, and caring for young. Thus, the area of a home range is an important indicator of an animal's behavioural and energetic requirements. While several studies have identified the factors that influence home range area (HRA), none of them has investigated global patterns of HRA among and within snake species. Here, we used a phylogenetic mixed model to determine which factors influence HRA in 51 snake species. We analysed 200 HRA estimates to test the influence of body mass, sex, age, diet, precipitation, latitude, winter and summer temperature, while controlling for the duration of the study and sample size. We found that males had larger HRA than females, that adults had larger HRA than juveniles, and that snake species with fish-based diets had smaller HRA than snake species with terrestrial vertebrate-based and invertebrate-based diets. We also found that HRA tended to increase as mean winter temperature decreases and tended to decrease with precipitation. After accounting for these factors, the phylogenetic heritability of HRA in snakes was low (0.21 ± 0.14). Determining the factors that dictate macroecological patterns of space use has important management implications in an era of rapid climate change.


Constructing internal audit quality evaluation index: evidence from listed companies in Jiangsu province, China.
Internal audit quality is the foundation for a company's survival and development across the world. As a result, global efforts have been made to develop a scientific and accurate evaluation index for internal audit quality. However, literature shows that existing internal audit quality evaluation indices have many flaws, such as a lack of systematic internal audit evaluation indicators, poor execution, and inability to identify priority areas. To address gaps in the literature, this study intended to construct an internal audit quality evaluation index utilizing the joint approaches of the Balanced Scorecard, Delphi Process, and Analytical Hierarchy Process. A systematic literature review, examination of companies' internal audit guidelines, Balanced Scorecard, and Delphi approaches resulted in a multilevel internal audit quality evaluation index with five dimensions (stakeholder satisfaction, stakeholder contribution, financial results, internal audit process, and learning and growth) and 36 indicators. The Analytical Hierarchy Process revealed that the most prioritized dimension is the internal audit process. The consistency ratio and evaluation feedback from the listed companies' internal auditors, management, and audit committee members revealed that the results are valid and reliable.


Surveys of Norwegian youth indicated that breast feeding reduced subsequent risk of obesity.
Breast-feeding protects against overweight in childhood, while it is uncertain if it is protective against adolescent and adult overweight. The objective of this study was to examine whether having been breast fed protects against adolescent and adult overweight and obesity. Participants in the Oslo Youth study examined in 1979/1981 (n=635, mean age 13.1 years) and in 1999. Weight and height were measured in 1979/1981 and self-reported in 1999. Breast-feeding information was provided by the parents in 1979/1981. Potential confounders adjusted for included parents' body mass index and education, mother's smoking habits, participants' physical activity, smoking status, education and energy intake. Comparing those having been breast fed more than 3 months with those never breast fed, the adjusted odds ratios (95% confidence interval [CI]) between the two groups were 0.27 (0.13-0.56) for being overweight and 0.15 (0.03-0.72) for being obese in adolescent. In adulthood, the corresponding odds ratios were 0.64 (0.33-1.26) and 0.34 (0.12-1.01), respectively. Breast feeding during infancy appears to protect against adolescent overweight and obesity, while the effect on adult weight status is weaker. With increasing age, the impact of any protective physiologic mechanisms of breast feeding seen earlier in life tends to diminish.


Panic in the Pandemic: When Should Kidney Transplant Programs Close?
Pandemics greatly interfere with overall health care delivery as resources are diverted to combat the crisis. Kidney transplantation programs were closed temporarily during the COVID-19 pandemic. Given the critical shortage of organs, their short shelf life, and their overall importance to improving length and quality of life for those with kidney disease, this analysis examines the impact of discarding deceased donor organs. The net benefit (or harm) of discarding deceased donor organs was measured in projected life years from a societal and individual perspective using a Markov model. A wide range of infection rates, pandemic durations, and case fatality rates associated with infection in wait listed and transplant recipients were examined. Overall, patient life expectancy fell for both wait listed and transplant recipients as the pandemic conditions became more unfavorable. However, the overall net benefit of a transplant during the pandemic was preserved. For example, prior to the pandemic, the net benefit of a kidney transplant over dialysis was calculated to be 6.25 life years (LYs) or 8.24 quality-adjusted life years (QALYs) in a 40-year old recipient. This fell to 5.86 LYs (7.78 QALYs) during the pandemic. Even assuming plausible but higher relative case fatality rates and risks of nosocomial and donor transmission in transplant recipients compared to wait listed patients, the net benefit remained >4 years for most deceased donor organs. As long as hospitals have adequate resources to deal with the pandemic and can limit nosocomial infection, kidney transplantation should not be curtailed.


Cicaprost inhibits metastases of animal tumors.
Since an involvement of platelet aggregation in the metastatic process has been found, platelet activation inhibitors were investigated for their potential to reduce tumor metastases. Recent in-vitro and in-vivo investigations showed an antimetastatic effect of prostacyclin (PGI2) and stable prostacyclin analogues. This study concentrates on the effect of the stable prostacyclin analogue Cicaprost (Schering AG) on tumor metastases in two metastasizing tumors of rodents. C57BL/6 mice bearing s.c.-implanted M5076 reticulum sarcoma were treated with Cicaprost in doses of 0.1-1.0 mg/kg throughout the experiment. Cicaprost in all doses tested reduced the number of liver metastases in a statistically significant manner. The 1.0 mg/kg dose, which decreases the median number of liver metastases to more than 93% compared to the control, was most effective. Cicaprost in the 0.5 mg/kg dose reduced the number of liver metastases in mice bearing i.v.-implanted M5076 reticulum sarcoma. In Cop-Fisher rats bearing s.c.-implanted spontaneously metastasizing R3327 MAT Lu prostate carcinoma, Cicaprost in a dose of 1.0 mg/kg p.o. daily strongly reduced the number of lung metastases. These results indicate that Cicaprost is a potent inhibitor of tumor metastases in different tumor models in rodents.


Dynamic mechanical properties of dental nanofilled light-cured resin composites: Effect of food-simulating liquids.
This work is aimed at the study by dynamic mechanical analysis (DMA) of viscoelastic properties that is, the elastic modulus (E'), the loss modulus (E″), the loss tangent (tanδ) and the glass transition temperature (T(g)), of two current commercial light-cured resin composites, Filtek Supreme Body and Filtek Supreme Translucent, characterized as nanofilled. These composites show differences in the filler content and type. For DMA analysis the bar-shaped specimens were divided into groups of three samples each. The first group consisted of dry samples measured 1 h after light-curing (at room temperature) during which they were placed in a desiccator at 37 °C. The other groups consisted of samples which had been stored in air, distilled water, artificial saliva SAGF or ethanol/water solution (75 v/v), at 37±1 °C for 1, 7, 30 or 90 days. DMA tests were performed on a Diamond Dynamic Mechanical Analyzer (Perkin-Elmer) in bending mode. A frequency of 1 Hz was applied and a temperature range of 25-185 °C, while a heating rate of 2 °C/min were selected to cover mouth temperature and the materials' likely T(g). The studied dry composites showed comparable values for their properties in spite of their differences in the filler content and type. Storage of composites in air 37 °C for 1 day caused a significant post curing which was not continued during storage up to 90 days. Water and artificial saliva showed the same effect on composites. They caused both post curing and plasticization. Ethanol/water solution 75% v/v had a more strong effect than water and artificial saliva due to its organophilic nature. It caused post curing, plasticization and most probably degradation of the bond filler-silane coupling agent.


Autoradiographic visualization of CNS receptors for vasoactive intestinal peptide.
Receptors for VIP were characterized in the rat CNS. 125I-VIP bound with high affinity to rat brain slices. Binding was time dependent and specific. Pharmacology studies indicated that specific 125I-VIP binding was inhibited with high affinity by VIP and low affinity by secretin and PHI. Using in vitro autoradiographic techniques high grain densities were present in the dentate gyrus, pineal gland, supraoptic and suprachiasmatic nuclei, superficial gray layer of the superior colliculus and the area postrema. Moderate grain densities were present in the olfactory bulb and tubercle, cerebral cortex, nucleus accumbens, caudate putamen, interstitial nucleus of the stria terminalis, paraventricular thalamic nucleus, medial amygdaloid nucleus, subiculum and the medial geniculate nucleus. Grains were absent in the corpus callosum and controls treated with 1 microM unlabeled VIP. The discrete regional distribution of VIP receptors suggest that it may function as an important modulator of neural activity in the CNS.


Dimethyl 2-methyl-1,2-dihydro-quinoline-2,4-dicarboxyl-ate.
In the crystal of the title compound, C(14)H(15)NO(4), pairs of inter-molecular N-H⋯O hydrogen bonds link the mol-ecules into centrosymmetric R(2) (2)(10) dimers. These dimers are further connected via inter-molecular C-H⋯O hydrogen bonds, forming a three-dimensional network. The heterocyclic ring adopts a twisted conformation.


Systematic review with meta-analysis: the impact of a depressive state on disease course in adult inflammatory bowel disease.
Despite a higher prevalence of psychosocial morbidity in Inflammatory Bowel Disease (IBD), the association between depressive state and disease course in IBD is poorly understood. To investigate the impact of depressive state on disease course in IBD. We conducted a systematic review in MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and PsychINFO for prospective studies evaluating the impact of baseline depressive state on subsequent disease course in adult IBD. Eleven studies matched our entry criteria, representing 3194 patients with IBD. Three reported on patients with ulcerative colitis (UC), four included patients with Crohn's disease (CD) exclusively, and four studies included both UC and CD. Five studies reported an association between depressive state and disease course. None of the UC-specific studies found any association. In three of four CD-specific studies, a relationship between depressive state and worsening disease course was found. In four of five studies including patients in remission at baseline, no association between depressive state and disease course was found. Pooled analysis of IBD studies with patients in clinical remission at baseline identified no association between depressive state and disease course (HR 1.04, 95%CI: 0.97-1.12). There is limited evidence to support an association between depressive state and subsequent deterioration in disease course in IBD, but what data that exist are more supportive of an association with CD than UC. Baseline disease activity may be an important factor in this relationship. Further studies are needed to understand the relationship between mental health and outcomes in IBD.


The field dependence of NMR imaging. I. Laboratory assessment of signal-to-noise ratio and power deposition.
A method is proposed for measuring on the bench the NMR signal-to-noise ratio of rf probes, (over the range 1-100 MHz) and also the power deposited in patients during the imaging experiment. The technique is based on the principle of reciprocity, in that a direct relationship exists between the magnetic field generated (upon transmission) by a matched probe coil and the signal-to-noise ratio delivered by the same coil when used as a receiver. The construction and use of a calibrated sense coil for measuring the field is described, and the precautions and theory necessary for accurate measurement and understanding are outlined. Finally, the method is verified by comparison with a direct spectral measure of sensitivity obtained from a small doped water sample placed in NMR imaging equipment.


Molecular and biochemical characterization of the Mexican axolotl CD3 (CD3ε and CD3γ/δ).
In mammals, the T-cell receptor (TCR) complex expressed on mature T-cells consists of α/β or γ/δ clonotypic heterodimers non-covalently associated with four invariant chains forming the CD3 complex (CD3γ, CD3δ, CD3ε and CD3ζ). The TCR is the unit implicated in the antigenic peptide recognition whereas the CD3 subunits present as three different dimers (δ-ε, γ-ε and ζ-ζ) in the receptor complex participate to the signal transduction and are indispensable for the expression of the TCR at the cell surface. We report the cloning, characterization and expression analysis of CD3γ/δ and CD3ε genes in an amphibian urodele, the Mexican axolotl. Amino acid comparisons show that important motifs and residues were preserved between the axolotl CD3 chains and various vertebrate CD3ε, CD3γ, CD3δ and CD3γ/δ chains. During ontogeny, CD3ε transcripts are first detected in the dorsal region of tail-bud embryos before thymus organogenesis. CD3γ/δ transcripts are first detected in the head of 4-week-old larvae. A cross-reactive polyclonal anti-CD3ε antibody was used for the co-immunoprecipitation of the two CD3 proteins of 25 and 29 kDa, respectively, associated with the 90-kDa αβ TCR heterodimer.


Overview of the safety of felodipine based on clinical trials in patients with hypertension.
All clinical studies of at least 1 week's duration with felodipine in patients with hypertension were included in a safety analysis. The major finding was that felodipine does not increase mortality or the incidence of major cardiovascular events and that the data indicate a favorable effect.


Role of LGI1 protein in synaptic transmission: From physiology to pathology.
Leucine-Rich Glioma Inactivated protein 1 (LGI1) is a secreted neuronal protein highly expressed in the central nervous system and high amount are found in the hippocampus. An alteration of its function has been described in few families of patients with autosomal dominant temporal lobe epilepsy (ADLTE) or with autoimmune limbic encephalitis (LE), both characterized by epileptic seizures. Studies have shown that LGI1 plays an essential role during development, but also in neuronal excitability through an action on voltage-gated potassium Kv1.1 channels, and in synaptic transmission by regulating the surface expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPA-R). Over the last decade, a growing number of studies investigating LGI1 functions have been published. They aimed to improve the understanding of LGI1 function in the regulation of neuronal networks using different animal and cellular models. LGI1 appears to be a major actor of synaptic regulation by modulating trans-synaptically pre- and post-synaptic proteins. In this review, we will focus on LGI1 binding partners, "A Disintegrin And Metalloprotease (ADAM) 22 and 23", the complex they form at the synapse, and will discuss the effects of LGI1 on neuronal excitability and synaptic transmission in physiological and pathological conditions. Finally, we will highlight new insights regarding N-terminal Leucine-Rich Repeat (LRR) domain and C-terminal Epitempin repeat (EPTP) domain and their potentially distinct role in LGI1 function.


A new species of genus Neoaloa Singh Kirti, 2015 from Bihar, India (Lepidoptera: Erebidae: Arctiinae: Arctiini).
A new species, Neoaloa cernyi Singh Joshi, sp. nov. is described from Gular-Ghat of Valmiki Tiger Reserve, Bihar, India. Additionally, the original combination of Aloa collaris Hampson, 1891, comb. rev. is restored.


Phosphorus bioaccessibility measured in four amino acid-based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice.
The aim of this study was to quantify the bioaccessibility of phosphorus from amino acid-based formulas (AAFs) under different digestive conditions. We developed in-vitro batch digestion models with stomach digestion at different pH mimicking the normal digestive condition and conditions representing use of acid-suppressive medication. To validate bioaccessibility findings, we devised a low phosphorus murine model to test phosphorus bioavailability under compromised digestive conditions using proton pump inhibitors (PPIs) to neutralize stomach pH. In vitro phosphorus bioaccessibility of AAFs Neocate® Infant and Neocate Junior ranged between 57% and 65% under normal digestive conditions for infants (stomach pH 3.5) and between 38% and 46% under conditions that simulated bypass of stomach acidification, which is comparable to control diet and two EleCare® AAFs. In vivo bioavailability analysis showed that both Neocate formulas were able to normalize plasma phosphorus levels when administered to low phosphorus mice along with PPIs (control diet + PPI 8 ± 0.4; Neocate Infant 10.1 ± 0.9; Neocate Junior 9.2 ± 0.6; EleCare Infant 8.6 ± 0.4; EleCare Junior 8.7 ± 0.5; n = 8-10; P < 0.0001 versus baseline 3.4 ± 0.2 mg/dL). In comparison, plasma phosphorus levels remained lower on the low phosphorus diet (5.7 ± 0.2 mg/dL). Furthermore, urinary phosphorus/creatinine and intact fibroblast growth factor 23 were significantly lowered by low phosphorus diet. In contrast, intact parathyroid hormone and 1,25-dihydroxy vitamin D decreased and increased, respectively, and these parameters likewise normalized in mice administered AAFs. The present findings indicated that phosphorus bioaccessibility in the in-vitro batch digestion model translates well into phosphorus bioavailability in mice even under compromised digestive conditions that bypass gastric acidification.


High expression of matrix metalloproteinases 16 is associated with the aggressive malignant behavior and poor survival outcome in colorectal carcinoma.
Recent evidence suggested an important role of matrix metalloproteinases 16 (MMP16) in the progression of several cancers. However, the contribution of MMP16 to colorectal cancer (CRC) remains elusive. In this study, we combined analyzed the MMP16 expression in The Cancer Genome Atlas (TCGA), GSE39582 database and in-house database. In TCGA and GSE39584 database, the log-rank test demonstrated that overall survival (OS) for patients with low MMP16 expression in tumor tissues was significantly higher than those with high expression (P < 0.05). In the validation cohort, high MMP16 expression was significantly correlated with N stage (P = 0.008) and lymphovascular invasion (P = 0.002). The 5-year OS and disease free survival (DFS) in high and low MMP16 expression groups were 66.0% and 80.6%, 54.3% and 72.8%, respectively. Univariate and multivariate analysis showed that high MMP16 expression was an independently prognosis factor for both OS and DFS (P < 0.05). Functional study found that silencing MMP16 expression could inhibit migration and invasion of colon cancer cells. In conclusion, high expression of MMP16 is associated with the aggressive malignant behavior and poor survival outcome of CRC patients. MMP16 can serve as an indicator of prognosis as well as a potential novel target for treatment of CRC patients.


Multiple myeloma involving the cricoid cartilage.
This presents a case report of a patient with multiple myeloma who developed such a lesion in the cricoid--a circumstance which has not previously been recorded.


Interplay between FAK, PKCδ, and p190RhoGAP in the regulation of endothelial barrier function.
Disruption of either intercellular or extracellular junctions involved in maintaining endothelial barrier function can result in increased endothelial permeability. Increased endothelial permeability, in turn, allows for the unregulated movement of fluid and solutes out of the vasculature and into the surrounding connective tissue, contributing to a number of disease states, including stroke and pulmonary edema (Ermert et al., 1995; Lee and Slutsky, 2010; van Hinsbergh, 1997; Waller et al., 1996; Warboys et al., 2010). Thus, a better understanding of the molecular mechanisms by which endothelial cell junction integrity is controlled is necessary for development of therapies aimed at treating such conditions. In this review, we will discuss the functions of three signaling molecules known to be involved in regulation of endothelial permeability: focal adhesion kinase (FAK), protein kinase C delta (PKCδ), and p190RhoGAP (p190). We will discuss the independent functions of each protein, as well as the interplay that exists between them and the effects of such interactions on endothelial function.


Survival of human periodontal ligament fibroblast cells in Cornisol and HBSS for transportation of avulsed teeth: a comparative ex vivo study.
Viability of periodontal ligament fibroblast cells (PDFC) is one of the key factors in determining the success of replantation of avulsed teeth. Extra-oral time and transport media are closely related to the same. The present study aims to evaluate and compare the efficiency of Cornisol, Hank's balanced salt solution (HBSS) and normal saline in preserving the viability of PDFC. The human PDFC were isolated from primary culture from freshly extracted human premolars. Effect of Cornisol, HBSS and normal saline on viability of isolated PDFC was assessed using standard MTT assay. The cells were exposed to the experimental solutions (Cornisol/HBSS/normal saline) for varying time points (30 min, 1 h, 24 h, 48 h and 96 h) and viability was determined by colorimetric MTT method by quantifying the amount of formazan crystal formed (optical density). Experiment was performed in triplicates and the data were subjected to statistical analysis. Statistical analysis was performed using the Kruskal-Wallis ANOVA with post hoc Bonferroni's test with a significance level of p value ≤.05. Cornisol ≥ HBSS > saline. Cornisol can be used as a storage media for avulsed teeth and is significantly more effective than HBSS in maintaining the periodontal ligament cell viability at tested time intervals.


Metabolomics and neuroanatomical evaluation of post-mortem changes in the hippocampus.
Understanding the human brain is the ultimate goal in neuroscience, but this is extremely challenging in part due to the fact that brain tissue obtained from autopsy is practically the only source of normal brain tissue and also since changes at different levels of biological organization (genetic, molecular, biochemical, anatomical) occur after death due to multiple mechanisms. Here we used metabolomic and anatomical techniques to study the possible relationship between post-mortem time (PT)-induced changes that may occur at both the metabolomics and anatomical levels in the same brains. Our experiments have mainly focused on the hippocampus of the mouse. We found significant metabolomic changes at 2 h PT, whereas the integrity of neurons and glia, at the anatomical/ neurochemical level, was not significantly altered during the first 5 h PT for the majority of histological markers.


Nucleoside triphosphate and cation requirement for dopamine uptake by plain synaptic vesicles isolated from rat cerebrums.
Plain synaptic vesicles were partially purified from rat cerebrums and their [3H]dopamine uptake was investigated. The addition of MgCl2 plus ATP and of CaCl2 plus ATP increased the uptake 16 times and 5.5 times, respectively, higher than the control level, whereas the separate addition of these agents augmented the level at most 2.5 times. GTP stimulated the uptake as well as ATP, whereas UTP was one-third as effective and CTP, ADP, and AMP were all ineffective. Adenylyl imidodiphosphate was not only ineffective, but strongly reduced the ATP-dependent uptake. The half-maximal level of the ATP-dependent uptake was reached within 1.5 min after the start of incubation at 25 degrees C. The incorporation peaked at 5-10 min, then gradually declined to half-maximum at 45 min. This decline was prevented by the further addition of small amounts of CaCl2. There was no uptake at 0 degrees C, and the incorporation rate was at least 2 times faster at 37 degrees C than it was at 25 degrees C. The apparent Michaelis constant for [3H] dopamine was 1.6 muM. The half maximal inhibition of uptake was obtained at 0.1 muM reserpine; neither colchicine nor ouabain showed significant inhibition. The ATP-dependent uptake was not affected by K+, Na+, and Cl-, but was drastically decreased by isotonic phosphate buffer.


Cardiovascular risk in patients achieving low-density lipoprotein cholesterol and particle targets.
Previous research suggests that LDL particle number (LDL-P) may be a better tool than LDL cholesterol (LDL-C) to guide LDL-lowering therapy. Using real-world data, this study has two objectives: [1] to determine the incidence of CHD across LDL-P thresholds; and [2] to compare CHD/stroke events among patients achieving comparably low LDL-P or LDL-C levels. A claims analysis was conducted among high-risk patients identified from the HealthCore Integrated Research Database(SM). The impact of LDL levels on risk was compared across cohorts who achieved LDL-P <1000 nmol/L or LDL-C <100 mg/dL. Cohorts were matched to balance demographic and comorbidity differences. Among 15,569 patients with LDL-P measurements, the risk of a CHD event increased by 4% for each 100 nmol/L increase in LDL-P level (HR 1.04; 95% CI 1.02-1.05, p < .0001). The comparative analysis included 2,094 matched patients with ≥12 months of follow-up, 1,242 with ≥24 months and 705 with ≥36 months. At all time periods, patients undergoing LDL-P measurement were more likely to receive intensive lipid-lowering therapy and had a lower risk of CHD/stroke than those in the LDL-C cohort (HR: 0.76; 95% CI: 0.61-0.96; at 12 months). In this real-world sample of commercially insured patients, higher LDL-P levels were associated with increased CHD risk. Moreover, high-risk patients who achieved LDL-P <1000 nmol/L received more aggressive lipid-lowering therapy than patients achieving LDL-C <100 mg/dL, and these differences in lipids and therapeutic management were associated with a reduction in CHD/stroke events over 12, 24 and 36 months follow-up.


Helicobacter pylori infection is correlated with the incidence of erosive oral lichen planus and the alteration of the oral microbiome composition.
Oral lichen planus (OLP), a common clinical oral disease, is associated with an increased risk of malignant transformation. The mechanism underlying the pathogenesis of OLP is unknown. Oral dysbacteriosis is reported to be one of the aetiological factors of OLP. Although Helicobacter pylori infection is associated with various oral diseases, the correlation between H. pylori infection and OLP is unclear. This study aimed to investigate the effect of H. pylori infection on OLP pathogenesis and oral microbiome composition in the Chinese population, which has a high incidence of H. pylori infection. In this study, saliva samples of 30 patients with OLP (OLP group) and 21 negative controls (NC group) were collected. H. pylori infection was detected using the carbon-13-labeled urea breath test (UBT). The saliva samples were divided into the following four groups based on the H. pylori status: H. pylori-positive OLP (OLP+), H. pylori-positive NC (NC+), H. pylori-negative OLP (OLP-), and H. pylori-negative NC (NC-). Oral microbiome compositions were significantly different between the OLP and NC groups and between the OLP- and OLP+ groups. Compared with those in the OLP- group, those in the OLP+ group had a higher incidence of erosive OLP and higher levels of salivary cytokines. In contrast, the oral microbiome composition and cytokine levels were not significantly different between the NC- and NC+ groups. This is the first report to demonstrate that H. pylori infection is significantly correlated with the pathogenesis of erosive OLP.


A long-term follow-up study of first episodes of idiopathic status convulsivus in childhood: in relation to subsequent epilepsy (second report).
Fifty-four idiopathic status convulsivus (SC) cases were followed prospectively for a period between 5 and 21 years, the average being 13 years. Three-fourths of the cases had no residuals. There were two patterns of subsequent epilepsy; 1) complex partial seizures (CPS) with or without secondarily generalization (GTS) developed 4.3 +/- 3.5 years after febrile SC, 2) unilateral seizures or CPS +/- GTS developed 1.2 +/- 1.0 years after afebrile SC. The seizure prognosis of these cases was good except for some cases in the former group. There have been two kinds of theories regarding SC and epilepsy until now. One was derived from retrospective studies: SC and/or complex febrile convulsion (FC) were considered the main causes of temporal lobe epilepsy (TLE) producing mesial temporal sclerosis (MTS). Another was derived from prospective studies, in which the relation between FC and TLE was considered weak. Our results revealed that 6 cases (15%) out of 30 febrile SC developed epilepsy, and that five of those six cases were diagnosed as CPS. Three of 5 CPS cases were diagnosed as TLE. Recently the seizure prognosis of operative therapy for TLE--especially the MTS type--has been very favorable. Furthermore, it has become easy to find MTS by Magnetic Resonance Imaging (MRI). So, we emphasize that a precise follow-up study of SC using MRI, EEG, etc., is important in deciding the appropriate therapy for TLE, as well as in the study of the pathogenesis of TLE.


New strategies for base frame fabrication in microtia reconstruction.
The base frame provides a stable support for the helix, antihelix, and tragus-antitragus complex in microtia reconstruction, and this support is vital to attain a highly defined outline for a reconstructed auricle. The success of base frame sculpting depends on appropriate treatment of the cartilage, mainly the sixth and seventh costal cartilages, which may have different characteristics. The aim of this study was to demonstrate the relevant details for base frame fabrication under various scenarios. Between 2016 and 2019, a total of 352 patients with microtia underwent autologous auricular reconstruction. Concerning the different sizes and characteristics of the costal cartilage used for the base frame reconstruction, we describe the related methods for fabrication and introduce corresponding strategies for proper management. We found that 90% of the patients responded at follow-up, and 76% of them were satisfied with the cosmetically refined auricle with harmonious integrity. The elaborate design and appropriate utilization of costal cartilage for base frame sculpting is one of the most significant and fundamental processes in microtia reconstruction. It contributes to achieving a clearly defined outline of the auricle with harmonious integrity, which is as important as the other projected subunits.


Green microsaponification-based method for gas chromatography determination of sterol and squalene in cyanobacterial biomass.
Sterol analysis of complex matrices can be very laborious. To minimize the existing drawbacks, a new micro-method of sterols and squalene determination in cyanobacteria was developed and applied to monitor their production of Phormidium autumnale cultured heterotrophically. Sample extraction/saponification and GC analysis of the target compounds were optimized separately using Plackett-Burman design (PB) followed by a central composite rotational design (CCRD). The most influential variables were identified to maximize compound recovery. Chloroform presented the highest capability to extract all target compounds with a horizontal shaker table (HST) for homogenization in the saponification step. For the pretreatment, a small amount of chloroform was used for 90 min at 50 °C and 6 min for the saponification time. The sample introduction in the GC injector was studied by evaluating pressure and injector temperature. High response for sterols and squalene were obtained between 19 and 23 psi and at 310 °C of injection temperature. The new method was able to determine different sterol concentrations: 0.2-0.6 mg kg-1 of squalene, 5-18 mg kg-1 of stigmasterol, 6 mg kg-1 of cholesterol, and 3 mg kg-1 of β-sitosterol, showing high analytical performance and fulfilling all steps, thus proving to be a promising technique.


Assessing the "negative effect" and "positive effect" of COVID-19 in China.
The COVID-19 pandemic lockdowns led to a sharp drop in socio-economic activities in China in 2020, including reductions in fossil fuel use, industry productions, and traffic volumes. China's economy suffered a serious negative effect from COVID-19. However, there is a "positive effect" on CO2 emissions reduction. Here, for the first time, this paper constructs a new model named "Weighted Multi-regional Hypothetical Extraction Method (WMHEM)" based on a multiregional input-output model. It not only solves the problems of traditional HEM methods such as improper use of assumptions, excessive reliance on industry intermediate input, but also accurately reflects the impact of external shocks on the inter-industry linkages. By using the monthly economic data of each provinces in China during COVID-19 (except Hong Kong,Macao and Taiwan) an the latest Multi-regional input-output tables, the "economic negative effect" and "CO2 emission positive effect" under COVID-19 in China are measured. Results show that COVID-19 lockdown was estimated to have reduced China's CO2 emissions substantially between January and March in 2020, with the largest reductions in February. With the spread of coronavirus controlled, China's CO2 emissions rebounded in April. In addition, key emission reduction sectors and key development encouraged sectors are selected by combining "economic negative effect" and "CO2 emission positive effect" during COVID-19. Therefore, policies recommendations are put forward based on forward and backward linkages respectively which are from two ends of the supply chain to turn pandemic-related CO2 emissions declines into firm climate action.


Maternal age is a risk factor for caesarean section following induction of labour.
In Australia, more than 20% of women giving birth are 35 years or older. Advanced maternal age (AMA) is a risk factor for stillbirth, and many clinicians now recommend induction of labour (IOL) at around term gestation. The aim of this study is to determine if AMA is associated with emergency caesarean section (CS) following IOL. A retrospective cohort study was undertaken using routinely collected de-identified data. Live-born, singleton, cephalic, non-anomalous pregnancies undergoing IOL between 37 + 0 and 42 + 0 weeks were included. Previous CS and privately insured admission status were excluded. Mode of delivery was compared for women ≥38 years (AMA) and women <38 years. The primary outcome was birth by CS. Bivariate and multivariate logistic regression analyses were undertaken. A total of 7459 women were included (≥38 years n = 718, 9.6%; <38 years n = 6741, 90.4%). AMA women had similar rates of unassisted vaginal births (OR 1.15, 95% CI 0.98-1.35, P = 0.080) and CS (OR 1.08, 95% CI 0.90-1.30, P = 0.407) but fewer instrumental deliveries (OR 0.69, 95% CI 0.55-0.87, P = 0.002) compared to women <38 years. When controlled for confounders, AMA was independently associated with a two-fold increase in birth by CS following IOL (adjusted OR 2.29; 95% CI 1.64-3.20; P < 0.001). There were no differences in neonatal outcomes. Following IOL, AMA was associated with a two-fold increased likelihood of birth by CS in both nulliparous and multiparous women. However, the majority of AMA women birthed vaginally. Clinicians may find this information useful when counselling older women who are undergoing term IOL.


Research on the microstructure of insect cuticle and the strength of a biomimetic preformed hole composite.
The insect cuticle is a typical natural composite with excellent strength, stiffness, and fracture toughness. Scanning electron microscope observation of the microstructure of Hydrophilidae (an insect) cuticle showed several unique plies and structural characteristics, which may provide available information to the design of advanced composites. The microstructure found in the vicinity of pore canals in the insect cuticle was used for the design of the composite laminate with a hole. Compared with the composite laminate with a normally drilled hole, it was found that the strength of the specially designed composite laminate increases markedly, which is of important significance to the design of high-performance composites.


[Compositions and metabolic footprints of soil nematode communities under different alfalfa-crop planting patterns in semi-arid region of the Loess Plateau, Northwest China.]
Soil nematode communities play an important role in ecosystem material cycling and energy flow. In this study, soil samples were collected from three rotation systems in southern Ningxia mountainous region, including alfalfa continuous cropping (A-A), alfalfa-corn rotation (A-C), alfalfa-potato rotation (A-P). Soil physicochemical properties, nematode community composition and their metabolic footprints were measured. Compared with the A-A plot, the concentrations of soil organic carbon (SOC) and total nitrogen (TN) were significantly increased by 4.6% and 7.4% for SOC, 4.0% and 5.2% for TN in the A-C and A-P plots, respectively. Soil microbial biomass carbon and nitrogen were significantly higher in the A-C and A-P plots when compared with the A-A plot. The total abundance of soil nematodes in the A-C and A-P plots was higher by 49.5% and 93.7% than that in the A-A plot, respectively, with the dominant trophic group being changed to omnivores-predators from plant parasite. Compared to the A-A plot, the plant parasite index (PPI) was decreased significantly in the A-C and A-P plots, indicating that the harm of plant-parasites was reduced in soil food web. The nematode channel ratio (NCR) in the A-C and A-P plots were higher than that in the A-A plot, indicating that the role of bacterial decomposition was enhanced in soil organic matter decomposition. The maturity index (MI), the total nematode metabolic footprint, enrichment footprint, structure footprint in the A-C and A-P plots were all significantly higher than those in the A-A plot, suggesting that the structure and function of soil food web were more mature and stable, and the productivity and metabolic activity of nematodes were significantly enhanced. In general, the alfalfa-crop rotations improved soil nutrient status and reduced the disturbance degree of soil food web. Furthermore, soil ecosystem developed in the stable and healthy direction, which would be beneficial to the sustainable development of agriculture.


[Forensic medical expertise in Saint-Petersburg in the period from the XVIII and the early XX centuries: the sources and organization of the forensic medical expert activity].
This article contains information about the organization of the forensic medical expert investigation in the city of Saint-Petersburg since the time of its foundation. The sources of origin of the first Russian service of forensic medical expertise as a component of the state-supported healthcare system, as exemplified by the Saint-Petersburg state healthcare institution 'Bureau of Forensic Medical Expertise', are described.


One-pot synthesis of a new 2-substituted 1,2,3-triazole 1-oxide derivative from dipyridyl ketone and isonitrosoacetophenone hydrazone: Nickel(II) complex, DNA binding and cleavage properties.
An efficient and simple one-pot synthesis of a new 1,2,3-triazole-1-oxide via reaction between isonitrosoacetophenone hydrazone and dipyridyl ketone in the EtOH/AcOH at room temperature has been developed smoothly in high yield. The reaction proceeds via metal salt free, in-situ formation of asymmetric azine followed by cyclization to provide 1,2,3-triazole 1-oxide compound. It has been structurally characterized. The 1:1 ratio reaction of the 1,2,3-triazole 1-oxide ligand with nickel(II) chloride gives the mononuclear complex [Ni(L)(DMF)Cl2], hexa-coordinated within an octahedral geometry. Characterization of the 1,2,3-triazole compound and its Ni(II) complex with FTIR, 1H and 13C NMR, UV-vis and elemental analysis also confirms the proposed structures of the compounds. The interactions of the compounds with Calf thymus DNA (CT-DNA) have been investigated by UV-visible spectra and viscosity measurements. The results suggested that both ligand and Ni(II) complex bind to DNA in electrostatic interaction and/or groove binding, also with a slight partial intercalation in the case of ligand. DNA cleavage experiments have been also investigated by agarose gel electrophoresis in the presence and absence of an oxidative agent (H2O2). Both 1,2,3-triazole 1-oxide ligand and its nickel(II) complex show nuclease activity in the presence of hydrogen peroxide. DNA binding and cleavage affinities of the 1,2,3-triazole 1-oxide ligand is stronger than that of the Ni(II) complex.


How Increased Nodal Metastasis and Recurrence in Cribriform Adenocarcinoma Relate to Polymorphous Adenocarcinoma and Survival: A Systematic Review.
Recently, histologic grade was removed from salivary tumor nomenclature by the WHO to include disease of higher grade. One such entity, cribriform adenocarcinoma (CAC), is an aggressive group of polymorphous adenocarcinoma (PAC), with frequent nodal metastasis and locoregional recurrence. We aim to examine the biologic behavior of this disease as compared with the PAC general cohort inclusive of all subtypes. A systematic review of the literature on polymorphous adenocarcinoma and cribriform adenocarcinoma was completed. A descriptive analysis was performed for the following predictor variables: nodal and distant metastasis, in addition to recurrence. The outcome variables, disease free recurrence, and disease specific survival, where plotted using Kaplan-Meier curves. PAC and CAC both show median age of diagnosis in the sixth decade of life and a female predominance. CAC occurs most frequently in the tongue and PAC in the palate. The 2 groups show a similar biologic behavior in regards to incidence of distant metastasis (4.1 vs 5.5%), recurrence (12.5 vs 17.8%), and death from disease (3 vs 2.7%). However, there was an increased incidence of nodal metastasis in CAC (53%) as compared with that in PAC of all subtypes (14%). CAC exhibits more aggressive biologic behavior as compared with the PAC cohort. Although CAC is not an officially recognized entity, these tumors likely comprise a significant portion of the cases of PAC with poor outcomes and are deserving of attention and consideration for escalation in oncologic treatment.


Recovery of Model Pharmaceutical Compounds from Water and Organic Solutions with Alginate-Based Composite Membranes.
In this work, we combined the non-solvent induced phase separation (NIPS) and further cross-linking by cations towards the preparation of nanofiltration membranes based on sodium alginate, a biodegradable, natural polymer. Acetone, ethanol, toluene, and hexane were used as non-solvents, and cations of calcium, silver, and aluminum-for polymer cross-linking, respectively. Results showed the precipitation strength of non-solvent played a noticeable role in the membrane's performance; for instance, the toluene permeability changed by four orders of magnitude with the decrease of precipitation strength of the non-solvent: acetone (Ptoluene = 0.1 kg∙m-2∙h-1∙bar-1) < ethanol (3 kg∙m-2∙h-1∙bar-1) < hexane (41 kg∙m-2∙h-1∙bar-1) < toluene (415 kg∙m-2∙h-1∙bar-1). It was shown that simultaneous precipitation and crosslinking in aqueous solutions AlCl3 or AgNO3 must be used in the preparation of alginate membranes for the highly selective recovery of pharmaceutical compounds from organic media. These membranes show rejection R = 90-93% of substances with MW = 626 g/mol and ethanol permeability PEtOH = 1.5-2.5 kg∙m-2∙h-1∙bar-1. For the highly selective recovery of pharmaceutical compounds from water, the method of obtaining membranes must be changed. Precipitation in toluene and then crosslinking in aqueous solutions of AlCl3 or AgNO3 must be used sequentially instead of simultaneous precipitation and crosslinking in aqueous solutions of the same inorganic salts. The permeability of such membranes varied from 0.44 to 7.8 kg∙m-2∙h-1∙bar-1 depending on the crosslinking cation in the alginate. The rejection of model substances with MW 350 and 626 g/mol were on the level of 99%. Alginate membranes can be used to solve separation problems in the pharmaceutical field, for example, to isolate antibiotics from their extractants and remove the same antibiotics from aqueous pharmaceutical waste to prevent their accumulation in the environment and the emergence of resistant genes and bacteria.


Congruency in physician-EMT assessment.
The transport of 488 patients by Department of Health and Hospital (DHH) ambulances during a three-week period was studied in an effort to determine the operational effectiveness of the Point of Entry (POE) Plan in Boston. The Plan is based on an assumption that EMTs can correctly assess patients' medical problems. Comparisons of the physicians' diagnoses and the EMTs' assessments were made to establish the level of congruency for each of the seven care categories delineated. Several secondary univariate analyses were performed for their association with accuracy in patient assessment. Appropriate ambulance utilization also was reviewed based on the diagnosis and the circumstances of the incident. Findings supported the effectiveness of the assessment and transportation of emergency patients in the Boston emergency medical services system.


Redo Coronary Artery Bypass Grafting in the era of Advanced PCI.
To review the evidence behind the role and relevance of redo coronary artery bypass grafting (CABG) in the current practice of percutaneous coronary intervention (PCI). A comprehensive electronic literature search was performed to identify articles that discuss the practice of PCI and redo CABG in patients that require coronary revascularization. All relevant studies are summarized in narrative manner to reflect current indications and preference. The advancement in utilization of PCI has reduced the rate of redo CABG in patients with previous CABG that requires revascularization of an already treated coronary disease or a new onset of coronary artery stenosis. Redo CABG is associated with satisfactory perioperative outcomes but higher mortality at immediate postoperative period when compared to PCI. Redo CABG patients are less likely to develop comorbidities associated with revascularisation, but the operative mortality is higher and long-term survival rates are similar in comparison to PCI. There is a need for further research into the role of redo CABG in the current advanced practice of PCI.


Down-regulation of miR-219-5p increase the risk of cancer-related mortality in patients with prostate cancer.
Prostate cancer is a common malignancy in men that is difficult to treat and carries a high risk of death. miR-219-5p is expressed in reduced amounts in many malignancies. However, the prognostic value of miR-219-5p for patients with prostate cancer remains unclear. We retrospectively analysed data from 213 prostate cancer patients from 10 June 2012 to 9 May 2015. Overall survival was assessed by Kaplan-Meier analysis and Cox regression models. Besides, a prediction model was constructed, and calibration curves evaluated the model's accuracy. Of the 213 patients, a total of 72 (33.8%) died and the median survival time was 60.0 months. We found by multifactorial analysis that miR-219-5p deficiency increased the risk of death by nearly fourfold (HR: 3.86, 95% CI): 2.01 to 7.44, p<0.001) and the risk of progression by twofold (HR: 2.79, 95% CI: 1.68 to 4.64, p<0.001). To quantify each covariate's weight on prognosis, we screened variables by cox model to construct a predictive model. The Nomogram showed excellent accuracy in estimating death's risk, with a corrected C-index of 0.778. miR-219-5p can be used as a biomarker to predict death risk in prostate cancer patients. The mortality risk prediction model constructed based on miR-219-5p has good consistency and validity in assessing patient prognosis.


The A-1087IL-10 allele is associated with cardiovascular disease in SLE.
The risk of cardiovascular disease (CVD) in SLE patients is very high. It is therefore surprising that IL-10 has been discussed both as pathogenic in SLE and as an atheroprotective cytokine. In contrast, TNF is believed to be atherogenic and we recently reported that raised activity in the TNF-system is implicated in SLE-related CVD. Twenty-six (aged 52 +/- 8 years) female patients with SLE and a history of CVD (myocardial infarction, angina, stroke or claudication) were compared with 26 age-matched SLE patients without CVD (SLE controls) or 26 age-matched population controls. The -1087IL-10 gene polymorphism was determined by PCR with restriction endonuclease mapping. Serum IL-10 and TNF-levels were determined by ELISA. The A allele frequency of -1087IL-10 gene in SLE/CVD was higher than in SLE controls (0.62 versus 0.42, p < 0.05). Ten (38%) of 26 SLE/CVD exhibited IL-10 AA genotype compared with five (19%) of 26 SLE controls. Serum IL-10 and TNF-levels were raised in SLE/CVD compared with SLE controls or population controls (p < 0.001). Furthermore, in SLE/CVD, a significantly reduced IL-10:TNF ratio was observed in patients with IL-10 AA genotype compared with AG or GG genotype (0.56 versus 0.77 versus 1.24, p < 0.05). In SLE controls and population controls, individuals with IL-10 GG genotype tended to have higher IL-10:TNF ratio. In conclusion, the A-1087IL-10 allele which has been reported to cause a lower capacity for IL-10 production could contribute to CVD in SLE. Furthermore, the IL-10 AA genotype is associated with reduced ratio of atheroprotective to atherogenic cytokines in SLE patients with CVD.


Appearance of prolactin-releasing peptide-producing cells in the area postrema of postnatal rats.
Prolactin-releasing peptide (PrRP) was recently isolated from bovine hypothalamus. PrRP is the natural ligand for an orphan G-protein-coupled receptor, hGR3, and directly stimulates prolactin secretion from the anterior pituitary in vitro and in vivo. It has also been reported that PrRP plays an important role as a neurotransmitter and/or neuromodulator in the brain. Although much knowledge has been gained concerning PrRP in the adult rat brain, little attention has been paid to the fetal and postnatal stages. We therefore examined the development of PrRP neurons in the rat brain. In immunocytochemical and in situ hybridization experiments, we observed the transient appearance of PrRP-producing cells in the area postrema (AP), in which PrRP-producing cells do not exist in the normal adult rat. PrRP-producing cells in the AP were detected at P14, and many PrRP-producing cells were observed at P17, though none were detected at P19. This is the first report of the appearance of PrRP-producing cells in the postnatal AP. Our findings suggest that PrRP may play a previously unknown role in the AP of postnatal rats.


Identification of target and function specific antibodies for effective drug delivery.
Phage antibody technology is a powerful approach for generating human antibodies to virtually any target antigen. For many therapeutic applications, it is useful to generate antibodies that bind to cell-surface receptors in a manner where binding results in internalization of the antibody. This allows use of the antibody to deliver toxic payloads intracellularly to achieve a therapeutic effect. Here we describe how phage antibody libraries can be directly selected on tumor cell lines to generate antibodies binding cell-surface receptors and which are rapidly internalized upon binding. Protocols are provided showing how to (1) directly select internalizing antibodies from phage antibody libraries; (2) screen phage antibodies in a high-throughput flow cytometry assay for binding to the tumor cell line used for selection; (3) identify the antigen bound by the phage antibody using immunoprecipitation and mass spectrometry; and (4) verify and quantitate such that phage antibodies are internalized.


The synergistic effect of microplastic and malathion exposure on fiddler crab Minuca ecuadoriensis microplastic bioaccumulation and survival.
We assessed the combined effects of polyethylene microplastic (MP) and malathion (MLT) on the survival of the fiddler crab Minuca ecuadoriensis, and MP tissue bioaccumulation in four treatments following 120 h exposure: T1) Control; T2) MLT 50 mg L-1; T3) MP 200 mg L-1; and T4) MLT (50 mg L-1) + MP (200 mg L-1). The highest mortality (80%) was in T4, followed by T2 (28%) and no mortality was in T3. Higher MP bioaccumulation was observed in T4 (572 items g tissue-1) followed by T3 (70 items g tissue-1). Our findings indicate that the synergistic effect of MLT and MP increased M. ecuadoriensis bioaccumulative capacity and decreases survival. Thus, as MP contamination in aquatic environments is ubiquitous, our study raises a warning on the synergistic effects of MP with other environmental contaminants and serves as a baseline for further studies.


A sensitive bioassay for lipase using bacterial bioluminescence.
A new bioassay for lipase utilizes a dim mutant of luminous bacteria which emit light upon the addition of long chain fatty acids, especially myristic acid. The luminescence response is proportional to the amount of added myristic acid over a 100-fold range, down to 10 nM. Trimyristin was used as a substrate for lipase and the hydrolyzed myristic acid was determined by the response of the luminous bacteria either on a continuous basis in the same reaction mixture or alternatively, when the hydrolytic stage is done separately followed by the independent detecting system. Using these procedures it is possible to assay lipase activity at rate corresponding to a release of as low as 10 pmol myristic acid per min.


A novel and simple approach to element fractionation analysis: Single step fractionation of milk.
A novel single step fractionation of cow's milk was achieved using ethyl ether, n-hexane and isopropyl alcohol (3:3:4) mixture via solubility difference and precipitation. Milks were separated into lipid, serum and protein fractions. The distribution of elements was determined by ICP OES and validated by the analysis of NIST-1549a. The applicability of the scheme was tested by the analysis of whole, skimmed, semi-skimmed and infant formula. The distribution tendency of each element was variable. The lipid and protein bound element concentrations ranged from 0.053 to 5.3 mg L-1 and 0.046-1111.2 mg L-1, respectively, whereas it was between 0.064 and 954.5 mg L-1 for the serum fraction. The trend of element distributions were in the order: protein > serum > lipid for the most elements, except for Mg, Na and K. This study provide practical and innovative way to elucidate the distribution of elements which may provide information to be applied in health and nutrition strategies.


Effects of blood glucose levels on aspirin-induced gastric mucosal damage.
In female rats aspirin-induced gastrin mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis. In vitro incubation of gastric mucosal homogenates showed that diburyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed.


Refractory Chronic Lymphocytic Leukemia with Central Nervous System Involvement: A Case Report with Literature Review.
There have been few reports on central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL). This is an extremely rare disease with poor prognosis, owing to resistance to various treatments. We describe a 33-year-old man with intractable CLL with CNS involvement. He was diagnosed with CLL, with diplopia as the first manifestation. Magnetic resonance imaging revealed a contrast-enhancing tumor in the right temporal lobe, which was diagnosed as CNS involvement in CLL on brain biopsy. High-dose methotrexate therapy was ineffective for this lesion, which was also resistant to subsequent whole-brain irradiation, treatment with fludarabine-cyclophosphamide-rituximab chemoimmunotherapy, and ibrutinib administration. Because no standard protocol exists for CLL with CNS involvement, it is important to accumulate case data to verify the choice of new drugs for administration at an early stage. Therefore, we also conducted a literature review of 50 case reports of CNS lesions in the last 10 years to consider the pathophysiology, diagnosis, and treatment of CNS involvement in CLL. The possibility of new therapeutic agents, eg, ibrutinib and venetoclax, or a combination of these agents and methotrexate, can be envisioned as a treatment strategy for CLL with CNS involvement.


Modified Microcoil for Preoperative Localization of Solitary Pulmonary Nodules: A Prospective, Single-Arm, Multicenter Clinical Study.
To evaluate the efficacy and safety of placement of a modified microcoil for precise preoperative localization of solitary pulmonary nodules (SPNs) before video-assisted thoracoscopic surgery (VATS). This prospective, single-arm, multicenter study included patients who underwent computed tomography (CT)-guided modified microcoil insertion prior to SPN resection by VATS between January 2018 and June 2018. The patient demographics, nodule characteristics, and histopathologic findings were recorded. The primary endpoints included efficacy and safety. A total of 96 patients (41 men and 55 women; mean age, 59.3 years ± 8.9) with 96 SPNs were eligible for enrolment in the study. The mean maximal transverse diameter of the nodules was 10.3 mm ± 5.2 (range, 8-20 mm). The mean time between CT-guided microcoil insertion and the start of the surgical procedure was 14.6 hours (range, 12-24 hours). The duration of the preoperative CT-guided microcoil localization procedure was 29 minutes ± 9 (range, 10-35 minutes), and the intraoperative fluoroscopy time was 0.7 minutes ± 0.7 (range, 0.5-3 minutes). The clinical success rate was 96.9% (93/96), and all nodules were successfully resected using VATS. One patient experienced asymptomatic pneumothorax, but there were no cases of pulmonary hemorrhage. SPN localization with the modified microcoil is feasible and safe. The modified microcoil can facilitate the thoracoscopic resection of SPNs.


Hepatic glutathione concentrations and the release of pyrrolic metabolites of the pyrrolizidine alkaloid, monocrotaline, from the isolated perfused liver.
We have examined the relationship between the metabolism of the pyrrolizidine alkaloid, monocrotaline, and glutathione concentration in the isolated, perfused rat liver. On perfusion of monocrotaline (300 microM) through the isolated liver, high concentrations (1.1 mM) of its metabolite glutathionyldehydroretronecine are released into bile, while much lower amounts (4.86 microM; 0.05 mumol/g liver) accumulate in the perfusate over a 1 hr perfusion period. Metabolite concentration in both the bile and perfusate increase when the level of monocrotaline perfused is increased to 900 microM. Metabolite release is also elevated in livers pretreated with phenobarbital. Monocrotaline perfusion lowered glutathione concentrations in the liver from 30 min onwards. Livers from animals treated with buthionine sulfoximine or chloroethanol showed much lower glutathione levels after 60 min perfusion. Livers from chloroethanol-treated (but not buthionine sulfoximine-treated) animals showed significantly lower release of pyrroles into the bile on perfusion with monocrotaline, but there is no effect on the rate of build-up of pyrrolic metabolites in the perfusate. We conclude that hepatic glutathione concentrations and the release of pyrrolic metabolites of monocrotaline mutually interact. Exposure of the liver to monocrotaline reduces glutathione concentrations, while marked depletion of liver glutathione concentration leads to a decrease in the release of monocrotaline metabolites.


Implantation of posterior chamber phakic intraocular lens for myopia and hyperopia - long-term clinical outcomes.
To evaluate long-term refractive outcomes of implantable collamer lens (ICL) implantation and late postoperative complications. We assessed outcomes of patients who underwent ICL implantation (type ICM V4 for myopia, ICH V3 for hyperopia, TICM V4 for astigmatism) in our department between 1998 and 2013. It comprised 62 eyes (40 myopic and 22 hyperopic). The average follow-up period was 10.5 years. We evaluated: uncorrected and best-corrected visual acuity (UCVA and BCVA), spherical equivalent (SE), ICL vault, endothelial cell density and late postoperative complications. In myopes, the average UCVA was 1.0±0.37 and BCVA 1.18±0.38, in hyperopes 0.78±0.19 and 1.14±0.18, respectively. The average SE in myopes, whose target refraction was emmetropia, was -0.6±0.83 Dsf, in hyperopes +0.73±0.93. Central ICL vault was 206.16μm±105.94, (range 10-427) in myopes, 195.5μm±109.09, (range 20-404) in hyperopes. The most common late postoperative complication was cataract formation. Three myopic eyes (7.5%) developed symptomatic anterior subcapsular opacities with loss of at least two lines of BCVA. Cataract significantly affecting visual acuity occurred in 5 myopic eyes (12.5%) and 2 hyperopic eyes (9.09%). In these eyes, ICL removal and cataract surgery was performed. In our experience, ICL implantation in moderate and high ametropia was effective and relatively safe. The most common late complication was cataract formation. This complication can be managed effectively surgically with good refractive outcomes without loss of BCVA.


Study on Schizochytrium sp. improving the growth performance and non-specific immunity of golden pompano (Trachinotus ovatus) while not affecting the antioxidant capacity.
A feeding experiment was conducted to determine the effects of Schizochytrium sp. on growth performance, antioxidant capacity and non-specific immunity in golden pompano (Trachinotus ovatus).Two diets were formulated with or without Schizochytrium sp. supplemented (D1:0% and D2: 3%) to feed fish for 8 weeks. Results showed that growth performance, feed intake and survival rate increased significantly with Schizochytrium sp. supplemented (P < 0.05). Feed coefficient rate (FCR) of golden pompano fed the diet supplemented with Schizochytrium sp. was significantly lower than that of fish fed the control diet (P < 0.05). No significant differences were found in antioxidant capacity both in transcriptional level, including nclear factor erythroid-2-related factor-2 (Nrf2), Kelch-like-ECH-associated protein (keap1), catalase (CAT), glutathione peroxidase (GSH-PX) and heme oxygenase 1 (HO-1) and enzyme activity, such as total antioxidant capacity (T-AOC), malondialdehyde (MDA) and superoxide dismutase (SOD) (P > 0.05). Gut amylase and lipase were significantly higher in dietary Schizochytrium sp. supplemented treatment than that in control group (P < 0.05). The relative peroxisome proliferator-activated receptor-α (PPARα) expression level in liver was significantly higher in Schizochytrium sp supplemented treatment than that in control one (P < 0.05). The mRNA expression of myeloid differentiation factor 88 (MyD88), IL-1R-associated kinases 4 (IRAK4), interferon regulating Factor 3 (IRF3), interferon regulating Factor 3(IRF7) and heat shock protein 70 (HSP70) were significantly lower in Schizochytrium sp. supplemented treatment than that in control one (P < 0.05). In Schizochytrium sp. supplemented diet, golden pompano had significantly longer villi length than that in control diet (P < 0.05); muscle thickness in Schizochytrium sp. supplemented diet was thicker than that in control one (P < 0.05) and there were more goblet cells in Schizochytrium sp. treatment (P < 0.05). After the rearing trial, an air exposure trial was conducted. Results showed that the air-exposure mortality (AEM) and mRNA expression level of Nrf2, keap1, CAT, GSH-PX and HO-1 showed no significant difference (P > 0.05). These results indicated that dietary Schizochytrium sp. improved the growth performance and non-specific immunity of golden pompano while made no difference to antioxidant capacity.


Age of First Exposure to Soccer Heading and Sensory Reweighting for Upright Stance.
US Soccer eliminated soccer heading for youth players ages 10 years and younger and limited soccer heading for children ages 11-13 years. Limited empirical evidence associates soccer heading during early adolescence with medium-to-long-term behavioral deficits. The purpose of this study was to compare sensory reweighting for upright stance between college-aged soccer players who began soccer heading ages 10 years and younger (AFE ≤ 10) and those who began soccer heading after age 10 (AFE > 10). Thirty soccer players self-reported age of first exposure (AFE) to soccer heading. Sensory reweighting was compared between AFE ≤ 10 and AFE > 10. To evaluate sensory reweighting, we simultaneously perturbed upright stance with visual, vestibular, and proprioceptive stimulation. The visual stimulus was presented at two different amplitudes to measure the change in gain to vision, an intra-modal effect; and change in gain to galvanic vestibular stimulus (GVS) and vibration, both inter-modal effects. There were no differences in gain to vision (p=0.857, η2=0.001), GVS (p=0.971, η2=0.000), or vibration (p=0.974, η2=0.000) between groups. There were no differences in sensory reweighting for upright stance between AFE ≤ 10 and AFE > 10, suggesting that soccer heading during early adolescence is not associated with balance deficits in college-aged soccer players, notwithstanding potential deficits in other markers of neurological function.


Clinical Mass Spectrometry Approaches to Myeloma and Amyloidosis.
The diagnosis of myeloma and other plasma cell disorders has traditionally been done with the aid of electrophoretic methods, whereas amyloidosis has been characterized by immunohistochemistry. Mass spectrometry has recently been established as an alternative to these traditional methods and has been proved to bring added benefit for patient care. These newer mass spectrometry-based methods highlight some of the key advantages of modern proteomic methods and how they can be applied to the routine care of patients.


The cost of HIV disease in Northern Italy: the payer's perspective.
Healthcare expenditures incurred by the Health Service for HIV-infected patients have not been reported in Italy. To present health care costs for HIV-infected patients in the Lombardy Region, in 2004-2007, to determine the clinical characteristics of HIV infection associated with costs. Retrospective, observational, budget impact study, based on information collected for the period 2004-2007, including hospitalizations, outpatient services, highly active antiretroviral therapy (HAART) and non-HAART drug utilization. Inclusion criteria includes: confirmed HIV infection, age ≥18 years, resident in Lombardy Region, and followed at the "L. Sacco" Hospital in Milan from 2004 to 2007. The mean total cost per year to provide healthcare to HIV-positive patients was rather stable (€ 9658.36 in 2004 and € 9745.65 in 2007 (+0.90%)); HAART represented more than 60% of the total cost. We found that hepatitis C virus coinfection was related to higher costs (€ 11,003.45 vs. € 8896.06), as well as CD4 cell count <200 cells/mm (€ 12,681.36 vs. € 9594.11 and € 9450.36 in 200-499 and ≥500 cells/mm, respectively). The mean total cost of HIV health care was higher in patients who initiated antiretroviral treatment before 1997 than in those who started after 1996. The mean total cost per year to provide health care to HIV-positive patients was stable during the period 2004-2007, with an increase of HAART percentage impact on the total cost. Several clinical characteristics of HIV-infected patients were significantly associated with cost variation.


[Diagnostic criteria for acute pancreatitis and evaluation of the severity].
A research group supported by grants from the Ministry of Health and Labor has recently proposed new diagnostic criteria of acute pancreatitis and scoring system to predict the severity of the disease. Comparisons with the present criteria and scoring system were described and their potential problems were briefly discussed.


Patterns of Physical Activity Adherence by Adolescents With Diabetes or Obesity Enrolled in a Personalized Community-Based Intervention.
The purpose of this study was to determine the feasibility of a personalized, 16-week community-based physical activity intervention for adolescents with diabetes or obesity and examine the weekly patterns of adherence to the intervention. Physical activity adherence was evaluated throughout the intervention using accelerometers in 46 adolescents with type 1 diabetes (N = 22), type 2 diabetes (N = 12), or obesity (N = 12) (age, 14.4 ± 1.5 years; 56.5% female; 61% Hispanic). Of these, 39 completed the intervention, and 7 did not. There were no differences in baseline anthropometric characteristics or fitness between the completers versus noncompleters. Completers began above 1060 metabolic equivalent (MET) min/wk-1and stayed above 900 MET min/wk-1 for ~4 weeks and declined 39 MET min/wk-1 until end of study. Noncompleters began at 924 MET min/wk-1 yet dropped below 800 MET min/wk-1 by end of week 1 and declined an average of 151 MET min/wk-1. Interestingly, self-report of barriers to activity were higher in completers versus noncompleters. Findings highlight that adolescents completing the intervention could sustain a prescribed level of personalized activity for at least 1 month but had steadfast declines in weekly activity. Even with individualized programs, factors other than barriers to activity need to be considered when designing approaches to physical activity adherence for adolescents with diabetes or obesity.


HYBID derived from tumor cells and tumor-associated macrophages contribute to the glioblastoma growth.
Glioblastoma is the most malignant tumor of the brain associated with poor prognosis and outcome, and hence there is an urgent need to develop novel treatments for glioblastoma. In this study, we focused on hyaluronan binding protein (HYBID, as known as CEMIP/KIAA1199), a protein involved in hyaluronan depolymerization in chondrocytes and synoviocytes. We previously reported that Hybid-deficient (KO) mice show accumulation of hyaluronan in the brain, and memory impairment. To elucidate the role of HYBID in glioblastoma pathogenesis, we knocked down HYBID in human glioblastoma cells using siRNAs and developed a murine orthotopic xenograft model in the Hybid KO mice. Downregulation of HYBID in glioblastoma cells resulted in inhibition of cell proliferation and migration, and increased cell death. The growth of glioblastoma cells implanted in the mouse brain was suppressed in Hybid KO mice compared to that in the wild-type mice. Interestingly, infiltration of macrophages in the glioblastoma tissue was decreased in Hybid KO mice. Using intraperitoneal macrophages derived from Hybid KO mice and glioma cell supernatants, we examined the role of HYBID in macrophages in the tumor environment. We showed that HYBID contributes to macrophage migration and the release of pro-tumor factors. Moreover, we revealed that HYBID can be a poor prognostic factor in glioma patients by bioinformatics approaches. Our study provides data to support that HYBID expressed by both glioblastoma cells and tumor-associated macrophages may contribute to glioblastoma progression and suggests that HYBID may be a potential target for therapy that focuses on the tumor microenvironment of glioblastoma.


Worldwide research tendency and hotspots on hip fracture: a 20-year bibliometric analysis.
We analyzed the overall knowledge structure, development trends, and research hotspots of 7684 publications related to hip fracture through the bibliometric method. Our results indicate this area has received more and more attention from researchers. Prevention of complications will be the focus of future studies. Hip fracture is an international public health problem, with high morbidity, mortality, and associated health care costs. Research on hip fracture has been developed rapidly in recent years, but no bibliometric studies have been performed. We aimed to identify the publication changes in scientific output relating to hip fracture over the past two decades. The scientific output relating to hip fracture from 2000 to 2019 was identified and selected from the Web of Science Core Collection. Excel 2019 was used to summarize the quantitative indicators including publication number, citations, H-index, journal's impact factors, and journal citation reports. VOS viewer and CiteSpace software tools were used for co-authorship, citation, co-citation, and co-occurrence analyses between countries, institutions, journals, authors, references, and keywords. Data were analyzed on November 13, 2020. A total of 7684 publications were extracted. The USA was the leading contributor in this field with the largest publications (1876, 24.41%), the most citations (75,423 times), and the highest H-index (124). The number of publications in the Western European region is 1.82 times higher than that of North America region, and 3.59 times that of Eastern Asia region. The most productive institutions on hip fracture were University of Maryland (160). Injury (506) had the highest number of publications, while Osteoporosis International (20,483 times) was the most co-cited journal. Magaziner J and Parker MJ were the key researchers. The keywords were stratified into five clusters: cluster 1 ("operative approaches study"), cluster 2 ("rehabilitation study"), cluster 3 ("osteoporosis study"), cluster 4 ("outcomes and complications study"), and cluster 5 ("epidemiology study"). For hotspots, "tranexamic acid" showed a relatively latest average appearing years of 2017.52, followed by "30-day-mortality," "readmission," and "length of stay." There will be an increasing number of publications on the hip fracture research based on the current global trends, and the USA stays ahead in this field. In terms of region, Western Europe had the greater impact than North America. It is recommended to pay attention to the promising hotspots, such as tranexamic acid, 30-day-mortality, readmission, and length of stay.


A human mutation in STAT3 promotes type 1 diabetes through a defect in CD8+ T cell tolerance.
Naturally occurring cases of monogenic type 1 diabetes (T1D) help establish direct mechanisms driving this complex autoimmune disease. A recently identified de novo germline gain-of-function (GOF) mutation in the transcriptional regulator STAT3 was found to cause neonatal T1D. We engineered a novel knock-in mouse incorporating this highly diabetogenic human STAT3 mutation (K392R) and found that these mice recapitulated the human autoimmune diabetes phenotype. Paired single-cell TCR and RNA sequencing revealed that STAT3-GOF drives proliferation and clonal expansion of effector CD8+ cells that resist terminal exhaustion. Single-cell ATAC-seq showed that these effector T cells are epigenetically distinct and have differential chromatin architecture induced by STAT3-GOF. Analysis of islet TCR clonotypes revealed a CD8+ cell reacting against known antigen IGRP, and STAT3-GOF in an IGRP-reactive TCR transgenic model demonstrated that STAT3-GOF intrinsic to CD8+ cells is sufficient to accelerate diabetes onset. Altogether, these findings reveal a diabetogenic CD8+ T cell response that is restrained in the presence of normal STAT3 activity and drives diabetes pathogenesis.


Site location and requirements for the installation of a nuclear magnetic resonance scanning unit.
The installation of a nuclear magnetic resonance unit in any diagnostic facility involves certain location and environmental requirements. Based on our experience with the FONAR QED 80 system, we have delineated the major factors which must be considered when planning for such an installation. The major requirements are location and space. Suggested layouts for the suite and the control room are included. Certain environmental specifications will vary depending on the location of the facility and the type of unit installed.