Evidence-based practice profiles among bachelor students in four health disciplines: a cross-sectional study.
Despite the recognition of integrating evidence-based practice (EBP) in educational programs, there is limited research about bachelor students' EBP profiles (EBP knowledge, attitudes and behaviour) in the health disciplines nursing, occupational therapy, physiotherapy and radiography. The aim of this study was to assess EBP profiles among bachelor students in health disciplines, and explore differences between health disciplines, educational institutions, students' assessment of EBP teaching and expectations of EBP performance. A survey using the 'Evidence-Based Practice Profile - Norwegian version' (EBP2-N) was conducted among final year bachelor students in health disciplines from four educational institutions. The questionnaire consisted of five domains (Relevance, Terminology, Confidence, Practice and Sympathy) and assessed the five steps of EBP. We performed regression analyses to analyse mean differences in domain scores between health disciplines, Cohen's d to illustrate the magnitude of the largest difference in each domain, Omega squared to describe portion of variance in domain scores, and Spearman's rho (rs) to assess the monotonic relationship between EBP2-N domains and assessment of EBP teaching and expectations of EBP performance, respectively. Students reported highest overall mean score for Relevance, with an estimated standardized mean of 81.2 (CI 95% = 80.4-82.0). The other EBP2-N domains had estimated standardized means of 54 and less. Statistically significant differences (p < 0.03) between health disciplines were observed for all domains. The largest mean difference was found for Relevance with highest score for occupational therapy and lowest for radiography, with an estimated Cohen's d of 1.11. Moderate positive associations were observed between Relevance scores and students' assessment of EBP teaching (rs = 0.31), and expectations of EBP performance from teachers (rs = 0.36). We also observed a moderate positive correlation between Confidence and students' assessment of EBP teaching (rs = 0.46). Bachelor students in health disciplines found EBP relevant, but revealed low understanding of EBP terminology, low confidence with EBP skills, and low use of EBP in clinical situations. We observed differences in EBP profiles between health disciplines and between educational institutions. The differences in scores raise questions about the understanding of EBP within disciplines, and the complexity of EBP in educational settings.


An interlaboratory comparison between similar methods for determination of melatonin, cortisol and testosterone in saliva.
An interlaboratory comparison study for melatonin, cortisol and testosterone in saliva in which five laboratories participated is reported in this study. Each laboratory blindly measured eight samples prepared from natural saliva spiked with melatonin, cortisol and testosterone in the range 0-579 pmol/L for melatonin, 0-90 nmol/L for cortisol, and 0-622 pmol/L for testosterone. The recovery of spiked material for melatonin ranged from 91-110%, from 83-100% for cortisol and from 80-94% for testosterone. The content of natural hormone in saliva was estimated to be between 0.278 and 6.90 pmol/L for melatonin, 0.56 and 6.72 nmol/L for cortisol and 11.9 and 73.8 pmol/L for testosterone. This indicates a large interlaboratory variation. The present study emphasizes the importance of external quality control for the analysis of melatonin, cortisol and testosterone in saliva.


TNF-alpha is involved in activating DNA fragmentation in skeletal muscle.
Intraperitoneal administration of 100 microg kg(-1) (body weight) of tumour necrosis factor-alpha to rats for 8 consecutive days resulted in a significant decrease in protein content, which was concomitant with a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumour necrosis factor-alpha-treated animals as compared with the non-treated controls. Analysis of muscle DNA fragmentation clearly showed enhanced laddering in the skeletal muscle of tumour necrosis factor-alpha-treated animals, suggesting an apoptotic phenomenon. In a different set of experiments, mice bearing a cachexia-inducing tumour (the Lewis lung carcinoma) showed an increase in muscle DNA fragmentation (9.8-fold) as compared with their non-tumour-bearing control counterparts as previously described. When gene-deficient mice for tumour necrosis factor-alpha receptor protein I were inoculated with Lewis lung carcinoma, they were also affected by DNA fragmentation; however the increase was only 2.1-fold. These results suggest that tumour necrosis factor-alpha partly mediates DNA fragmentation during experimental cancer-associated cachexia.


Anti-inflammatory and immunomodulatory activities of the extracts from the inflorescence of Chrysanthemum indicum Linné.
Chrysanthemum indicum Linné (CI) has a long history for the treatment of inflammation, hypertension and respiratory diseases in China. The purpose of the present study was to investigate the anti-inflammatory and immunomodulatory properties of the inflorescence or bud of CI extracts. The ethanol extract of CI (CIEE) was fractionated to a petroleum ether soluble fraction (CIPF), an ethyl acetate soluble fraction (CIEF), a butanol soluble fraction (CIBF) and a water soluble fraction (CIWF) successively. CIBF (150 mg/kg, p.o.) caused a significant inhibition on the auricle edema in mice. CIBF (150, 300 mg/kg, p.o.) not only significantly increased the delayed-type hypersensitivity (DTH) reaction induced by 2,4-dinitro-fluorobenzene (DNFB) but also significantly enhanced antibody generation by splenic cells of mice and IgG and IgM levels in mice sera in response to sheep red blood cells (SRBC) in cyclophosphamide (CP)-induced mice. Furthermore, CIBF (150, 300 mg/kg, p.o.) obviously potentiated the function of the mononuclear phagocytic system in CP-induced mice. The above results reveal that CIBF possesses anti-inflammatory, humoral and cellular immunomodulatory and mononuclear phagocytic activities, probably due to the presence of flavonoids.


Age-Friendly Care At The Emergency Department.
Mount Sinai Hospital in New York City is at the forefront of an innovative approach to geriatric emergency care.


Effect of aminophylline on regional perfusion distribution in the lungs.
Using ten normal dogs, the right upper lobe of the lung was isolated in vivo by a balloon catheter and was artificially ventilated with nitrogen, air, 60% oxygen in nitrogen, and 60% oxygen and 20% carbon dioxide in nitrogen, while the rest of the lungs maintained a spontaneous breathing of ambient air. Aminophylline did not show a vasodilating action under severe alveolar hypoxia (PAO2: ca. 40 mmHg); on the contrary, it seemed to potentiate hypoxic pulmonary vasoconstriction. When the regional alveolar oxygen tension became less hypoxic (PAO2: ca. 70 mmHg) or higher than that in the rest of the lungs which spontaneously breathed ambient air, aminophylline showed a definite vasodilating action. Aminophylline also showed a vasodilating action in alveolar hypercapnia in the presence of alveolar hyperoxia.


Zebrafish as a model to study PTPs during development.
Protein-tyrosine phosphatases (PTPs) have important roles in signaling, but relatively little is known about their function in vivo. We are using the zebrafish as a model to study the function of PTPs at the organismal, cellular and molecular level. The zebrafish is an excellent experimental model for the analysis of gene function. We have developed methods to quantitatively study effects of PTP knockdown or expression of (mutant) PTPs, particularly with respect to gastrulation cell movements. Moreover, we have studied the phosphoproteome of zebrafish embryos. In this review, we will discuss methods to manipulate the zebrafish genome and techniques that we have developed to assess developmental defects during gastrulation and to assess differences in the phosphoproteome.


Phototherapy for Itch.
Phototherapy is an effective treatment modality for many types of pruritus. Although the exact mechanisms by which phototherapy reduces itch vary across pruritic conditions, its effects may result from immune suppression and/or neural modulation. In this article, the authors review the efficacy of different types of phototherapy for common inflammatory and noninflammatory pruritic conditions and discuss common side effects, such as erythema and exacerbation of pruritus. Although phototherapy may be an effective and relatively safe option for skin-directed treatment of chronic itch, barriers may exist for individual patients.


Applying the syndemic framework to cancer research for effective cancer control in low- and middle-income countries.
Cancer burden is increasing rapidly globally, especially in low- and middle-income countries (LMICs), which already face a double burden of infectious diseases and other non-communicable diseases (NCDs). LMICs also struggle with poor social determinants of health, leading to cancer health disparities, such as delayed diagnoses and increased death rates due to cancer. Contextually, relevant research needs to be prioritised in these regions to ensure feasible, evidence-based healthcare planning and delivery for cancer prevention and control. A syndemic framework has been used to study the disease clustering of infectious diseases and NCDs across varied social contexts to understand how diseases interact adversely and how the wider environmental context and other socioeconomic factors contribute to poor health outcomes within specific populations. We propose using this model to study the 'syndemic of cancers' in the disadvantaged population of LMICs and suggest ways for the clear operationalisation of the syndemic framework through multidisciplinary evidence-generation models for the delivery of integrated, socially conscious interventions for effective cancer control.


Impact of the COVID-19 pandemic on the organisation of stroke care. Madrid Stroke Care Plan.
The overload of the healthcare system and the organisational changes made in response to the COVID-19 pandemic may be having an impact on acute stroke care in the Region of Madrid. We conducted a survey with sections addressing hospital characteristics, changes in infrastructure and resources, code stroke clinical pathways, diagnostic testing, rehabilitation, and outpatient care. We performed a descriptive analysis of results according to the level of complexity of stroke care (availability of stroke units and mechanical thrombectomy). The survey was completed by 22 of the 26 hospitals in the Madrid Regional Health System that attend adult emergencies, between 16 and 27 April 2020. Ninety-five percent of hospitals had reallocated neurologists to care for patients with COVID-19. The numbers of neurology ward beds were reduced in 89.4% of hospitals; emergency department stroke care pathways were modified in 81%, with specific pathways for suspected SARS-CoV2 infection established in 50% of hospitals; and SARS-CoV2-positive patients with acute stroke were not admitted to neurology wards in 42%. Twenty-four hour on-site availability of mechanical thrombectomy was improved in 10 hospitals, which resulted in a reduction in the number of secondary hospital transfers. The admission of patients with transient ischaemic attack or minor stroke was avoided in 45% of hospitals, and follow-up through telephone consultations was implemented in 100%. The organisational changes made in response to the SARS-Co2 pandemic in hospitals in the Region of Madrid have modified the allocation of neurology department staff and infrastructure, stroke units and stroke care pathways, diagnostic testing, hospital admissions, and outpatient follow-up.


Attack frequency and disease duration as indicators for brain damage in migraine.
The aim of this study was to pinpoint predilection sites of brain damage in migraine by quantitatively identifying morphometric and diffusion differences in migraineurs, compared with control subjects, and to assess whether migraine attack frequency and attack history are indicators for brain abnormalities in migraineurs. Previous clinical neuroimaging investigations introduced the concept of migraine as a progressive brain disease. They reported an increased risk of white matter hyperintensities (WMH) with increasing attack frequency in migraineurs. We investigated 28 patients with migraine, using high-resolution T1- and diffusion-weighted magnetic resonance imaging and optimized voxel-based morphometry to localize gray and WM density, and fractional anisotropy and apparent diffusion coefficient differences. We identified predilection sites of brain abnormalities in migraineurs in the frontal lobes, brainstem, and the cerebellum, and we show that both attack frequency and disease duration are indicators for brain damage in migraine. Our findings report an unbiased quantitative whole brain assessment of morphological abnormalities in migraine. This might help to identify indicators for migraine as a possibly progressive brain disease. In order to reveal the causes and consequences of brain damage in migraine, further neuroimaging studies have to investigate quantitative brain changes in a longitudinal design.


Four-dimensional analyses show that replication compartments are clonal factories in which Epstein-Barr viral DNA amplification is coordinated.
Herpesviruses must amplify their DNA to load viral particles and they do so in replication compartments. The development and functions of replication compartments during DNA amplification are poorly understood, though. Here we examine 2 functionally distinct replicons in the same cells to dissect DNA amplification within replication compartments. Using a combination of single-cell assays, computational modeling, and population approaches, we show that compartments initially were seeded by single genomes of Epstein-Barr virus (EBV). Their amplification subsequently took 13 to 14 h in individual cells during which their compartments occupied up to 30% of the nucleus and the nuclear volume grew by 50%. The compartmental volumes increased in proportion to the amount of DNA and viral replication proteins they contained. Each compartment synthesized similar levels of DNA, indicating that the total number of compartments determined the total levels of DNA amplification. Further, the amplification, which depended on the number of origins, was regulated differently early and late during the lytic phase; early during the lytic phase, the templates limited DNA synthesis, while later the templates were in excess, coinciding with a decline in levels of the viral replication protein, BMRF1, in the replication compartments. These findings show that replication compartments are factories in which EBV DNA amplification is both clonal and coordinated.


Activation of invariant natural killer T cells stimulates adipose tissue remodeling via adipocyte death and birth in obesity.
In obesity, adipose tissue undergoes dynamic remodeling processes such as adipocyte hypertrophy, hypoxia, immune responses, and adipocyte death. However, whether and how invariant natural killer T (iNKT) cells contribute to adipose tissue remodeling are elusive. In this study, we demonstrate that iNKT cells remove unhealthy adipocytes and stimulate the differentiation of healthy adipocytes. In obese adipose tissue, iNKT cells were abundantly found nearby dead adipocytes. FasL-positive adipose iNKT cells exerted cytotoxic effects to eliminate hypertrophic and pro-inflammatory Fas-positive adipocytes. Furthermore, in vivo adipocyte-lineage tracing mice model showed that activation of iNKT cells by alpha-galactosylceramide promoted adipocyte turnover, eventually leading to potentiation of the insulin-dependent glucose uptake ability in adipose tissue. Collectively, our data propose a novel role of adipose iNKT cells in the regulation of adipocyte turnover in obesity.


Variations in brain morphometry among healthy preschoolers born preterm.
Preterm birth is associated with an increased risk of neonatal brain injury, which can lead to alterations in brain maturation. Despite being born without the most significant medical consequences of preterm birth, infants born early remain at increased risk for subtle brain injury that affects future neurodevelopment and functioning. To investigate the gray matter morphometry measures of cortical thickness, cortical surface area, and sulcal depth using MRI at 5 years of age in healthy children born preterm. Cohort study. Participants were 52 children born preterm (<33 weeks gestational age) and 37 children born full term. Cortical segmentation and calculation of morphometry measures were completed using FreeSurfer version 5.3.0 and compared between groups using surface-based, voxel-wise analyses. The preterm group had a significantly thinner cortex in temporal and parietal regions while cortical thickness was significantly larger within occipital and inferior frontal regions. Surface area was significantly reduced within the fusiform gyrus. Sulcal depth was significantly lower within the posterior parietal and inferior temporal regions but greater in the middle temporal and medial parietal regions. Regional differences were found between preschoolers born preterm and full term in cortical thickness, surface area, and sulcal depth. Cortical thickness differences primarily overlapped with regions found in previous studies of older children and adults. Differences in sulcal depth may represent additional areas of maturational differences in preterm children. These findings likely represent a combination of delayed maturation and permanent alterations caused by the perinatal processes associated with preterm birth.


Morphology of the trabecular meshwork within monkey (Macaca speciosa) eyes after irradiation with the free-running Nd:YAG laser.
The long-term tissue response of monkey eyes to trabeculoplasty produced at the chamber angle by neodymium:YAG (Nd:YAG) laser (thermal mode) was investigated. Four weeks after irradiation, a monolayer of corneal-like endothelial cells extended over the trabeculum in impact zones, with partial occlusion of intertrabecular spaces; this condition persisted at all subsequent stages of observation (viz, up to 13 weeks). Both primary and secondary degeneration of trabecular endothelial cells occurred predominantly at the posterior border of the juxtacanalicular tissue, and continued throughout the observation period. Lysis and degradation of collagen fibrils were also prominent in this region, and collagen-phagocytosing cells could be seen at all stages. Although activated fibroblasts were marked in this zone, regeneration processes were, in general, less marked than those of degeneration. The significance of these findings in relation to the mechanism by which trabeculoplasty works is discussed.


Evaluation of the echocardiogram as an epidemiologic tool in an asymptomatic population.
An asymptomatic adult population of 196 men and women was studied with the echocardiogram to derive age- and sex-specific "normal" values for a number of clinically used echocardiograhic variables. The results are in general agreement with previously published normal values. Body position during the examination, age and sex influence the echocardiographic results; body surface area correction normalized most of these effects. The prevalence of occult abnormalities determined by the echocardiogram is 7%; the most common finding was mitral valve prolapse. Inter- and intraobserver variability was assessed. The interobserver differences found on analysis are statistically, but not clinically , significant. The echocardiogram appears to be a suitable tool to use in epidemiologic studies to detect selected cardiac abnormalities, but is limited for this purpose because some subjects in such a population cannot be adequately examined.


Sudden infant death syndrome and abnormal metabolism of thiamin.
Although it has been generally accepted that moving the infant from the prone to the supine position has solved the problem of sudden infant death syndrome (SIDS), it has been hypothesized that this is an insufficient explanation and that a mixture of genetic risk, some form of stressful incident and marginal brain metabolism is proportionately required. It is suggested that each of these three variables, with dominance in one or more of them, act together in the common etiology. Much has been written about the association of thiamin and magnesium but the finding of extremely high concentrations of serum thiamin in SIDs victims has largely caused rejection of thiamin as being involved in the etiology. The publication of abnormal brainstem auditory evoked potentials strongly suggests that there are electrochemical changes in the brainstem affecting the mechanisms of automatic breathing and the control of cardiac rhythm. The brainstem, cerebellum and limbic system of the brain are known to be highly sensitive to thiamin deficiency (pseudo-hypoxia) and the pathophysiology is similar to a mild continued deprivation of oxygen. Little attention has been paid to the complex metabolism of thiamin. Dietary thiamin requires the cooperation of the SLC19 family of thiamin transporters for its absorption into cells and recent information has shown that transporter SNPs may be relatively common and can be expected to increase genetic risk. Thiamin must be phosphorylated to synthesize thiamin pyrophosphate (TPP), well established in its vital action in glucose metabolism. TPP is also a cofactor for the enzyme 2-hydroxyacyl-CoA lyase (HACL1) in the peroxisome, emphasizing its importance in alpha oxidation and plasmalogen synthesis in cell membrane physiology. The importance of thiamine triphosphate (TTP) in energy metabolism is still largely unknown. Thiamin metabolism has been implicated in hyperemesis gravidarum and iatrogenic Wernicke encephalopathy has been reported when the patient is treated with hyperalimentation, in spite of the pharmaceutical doses of thiamin in the intravenous fluid. Defective glucose metabolism, the vital fuel for energy synthesis, particularly in brain, must affect the developing fetus and the pattern of subsequent neonatal health. Sudden death in an apparently healthy infant, occurring at 3-4months, has long been known to result from feeding the infant with thiamin deficient breast milk. The early investigators of the cause of beriberi considered that this form of sudden death was pathognomonic of the infantile form of the disease.


Cyclovirus Vietnam DNA in immunodeficient patients.
Cyclovirus Vietnam (CyCV-VN) is a CyCV detected in 2013 from cerebrospinal fluid (CSF) samples of patients with neurological disorders. Information on prevalence, pathogenesis and disease association of CyCV-VN is still very patchy. In this study, we have used a PCR assay targeting the Rep gene to investigate the prevalence of CyCV-VN infection in blood and CSF samples of 346 Italian subjects. Overall, 7% of blood samples were positive for CyCV-VN while the virus was not detected in any of the CSF samples. The prevalence of CyCV-VN was relatively high in HIV positive patients (21%), modest in patients with HBV or HCV infection (6%), and low in transplant recipient patients (2%). Positive patients showed low levels of CyCV-VN viremia. The virus was not detected in serum samples from healthy individuals. Longitudinal analysis of serum samples obtained from selected patients showed a stable or transient presence of circulating CyCV-VN. The present study is the first to demonstrate CyCV-VN DNA circulation in Italy and to cast light on some biological aspects of this novel virus of men.


Tuberculosis control in the era of HIV.
Without HIV, the tuberculosis (TB) epidemic would now be in decline almost everywhere. However, instead of looking forward to the demise of TB, countries that are badly affected by HIV are struggling against a rising tide of HIV-infected patients with TB. As a consequence, global TB control policies have had to be revised and control of TB now demands increased investment. This paper assesses what is being done to address the issue and what remains to be done.


Associations among Bullying Victimization, Family Dysfunction, Negative Affect, and Bullying Perpetration in Macanese Adolescents.
Bullying has become one of the most significant problem behaviors that school-aged adolescents face. The current study examines the strain-delinquency relationship by employing General Strain Theory as a guiding framework. "Strain" was operationalized as bullying victimization and family dysfunction, "delinquency" was operationalized as bullying perpetration, and "negative affect" was operationalized as anxiety and depression. Analyses were carried out based on a group of 2,139 Macanese schoolchildren. Using a structural equation modeling technique, the results revealed that exposure to family dysfunction and bullying victimization was associated with adolescents' negative affect, such as anxiety and depression. Contrary to our expectations, the indirect effect of victimization on bullying through negative affect was negative, though the mediation effect was relatively small and only significant in boys. In addition, gender analyses of invariance showed that male adolescents who experienced more family conflict and parental control were less likely to engage in bullying. This study could lead to further anti-bullying interventions and practical efforts designed to improve positive parenting and adolescents' interpersonal skills.


Current Role of Allogeneic Stem Cell Transplantation in Multiple Myeloma.
Major progress in the treatment of multiple myeloma has been made in the last several years. However, myeloma remains incurable and patients with high-risk cytogenetics or advanced stage disease have an even worsen survival. Only allogeneic transplantation may have curative potential in some patients. However, the high non-relapse mortality and incidence of chronic graft-versus-host disease have raised controversy regarding this procedure. In this review, we will address the role of upfront and delayed allogeneic transplant.


[Prokaryotic expression, purification and activity detection of the extracellular and intracellular domains of human IGF1R beta subunit].
To construct the prokaryotic expression vectors of extracellular domain (β-ED) and intracellular protein kinase domain (β-PKD) of insulin-like growth factor 1 receptor beta (IGF1R-β) subunit, purify the fusion proteins GST-IGF1R β-ED and GST-IGF1R β-PKD, and detect their activities. Human GST-IGF1R β-ED and GST-IGF1R β-PKD coding regions were amplified from human mammary cDNA library by PCR and cloned into the prokaryotic expression vector pGEX-KG. The fusion proteins GST-IGF1R β-ED and GST-IGF1R β-PKD were expressed in E.coli Rossate and purified by GST-Sepharose 4B beads. The expression of the fusion proteins were detected by Western blotting. The interactions of the proteins with mediator of epidermal growth factor receptor-2 (ERBB2)-driven cell motility (MEMO) protein were identified by GST pull-down assay. GST-IGF1R β-ED and GST-IGF1R β-PKD recombinant plasmids were successfully cloned. Double enzyme digestion and sequencing confirmed that the inserted fragments were identical to the target ones. The fusion proteins were successfully induced in Rossate and Western blotting showed the expression as expected. GST pull-down assay revealed that GST-IGF1R β-PKD could interact with MEMO in vitro. GST-IGF1R β-ED and GST-IGF1R β-PKD were successfully cloned and purified. In addition, GST-IGF1R β-PKD could interact with MEMO in vitro, which demonstrated the good activity of the purified proteins.


Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock.
To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II). Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period. A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms. PCT values were highest in patients with septic shock (12.89+/-4.39 ng/ml;P<0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91+/-3.87 ng/ml vs 0.53+/-2.9 ng/ml;P<0.001, and 0.41+/-3.04 ng/ml;P<0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26+/-1.62, 16.09+/-2.06, and 17.42+/-1.72 points, respectively), but was significantly higher in patients with septic shock (29.27+/-1.35,P<0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock. In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.


Roflumilast, a cyclic nucleotide phosphodiesterase 4 inhibitor, protects against cerebrovascular endothelial injury following cerebral ischemia/reperfusion by activating the Notch1/Hes1 pathway.
The loss of tight junction (TJ) and adherens junction (AJ) proteins leads to the damage of the blood-brain barrier (BBB) during cerebral ischemia. Inhibition of cyclic nucleotide phosphodiesterase 4 (PDE4) by roflumilast (Roflu) protects against ischemic stroke-induced neuronal damage. However, the effects of Roflu on vascular endothelial injury and BBB integrity remain unknown. Here, we investigated whether and how Roflu protects against cerebrovascular endothelial injury caused by cerebral ischemia/reperfusion. We demonstrated that PDE4B knocking-down increased the expression of TJ and AJ proteins in human brain microvascular endothelial cells (HBMECs) subjected to oxygen-glucose deprivation reperfusion (OGD/R). Inhibition of PDE4 by Roflu (1.0 μM) showed similar effects as PDE4B knocking-down. We then found that Roflu activated Notch1/Hairy and enhancer of split 1 (Hes1) signaling. Consistently, the effects of Roflu on TJ and AJ proteins were reversed by the γ-secretase inhibitor DAPT or Hes1 knocking-down. Furthermore, Roflu (1.0 mg/kg) improved neurobehavioral outcomes and ameliorated BBB disruption in rats following ischemic stroke. Roflu also increased the levels of TJ proteins and AJ proteins in vivo. Collectively, these data suggest that Roflu is a promising compound for the prevention of BBB damage. The protective effects of Roflu are mediated through activation of the Notch1/Hes1 pathway.


Associations of body dissatisfaction with anxiety and depression in the pregnancy and postpartum periods: A longitudinal study.
Pregnancy is a time of increasing vulnerability to the development of body dissatisfaction, anxiety, and depression. The present study aims to examine associations of body dissatisfaction with anxiety and depression at the following points: 6 months before pregnancy (retrospective report); in the first, second, and third trimesters of pregnancy; and up to 6 weeks postpartum. A prospective longitudinal design with a quantitative approach was adopted. A consecutive sample of 1,371 Chinese pregnant women in Hong Kong was assessed using standardized instruments at four time points. A mixed-effects model with repeated measures revealed that body dissatisfaction and depression symptoms changed across different stages of pregnancy. Hierarchical multiple regressions showed that, after adjusting for the identified risk factors, body dissatisfaction before and during pregnancy were positively associated with antenatal anxiety and depression symptoms. Concurrent body dissatisfaction was positively associated with postpartum depression symptoms. There was a high attrition rate in the follow-up assessments. Antenatal anxiety symptoms were assessed using the scale for general anxiety, which may not adequately capture the experience of anxiety among pregnant women. Primary healthcare practitioners should be made aware of body dissatisfaction among pregnant women in order to facilitate early intervention for anxiety and depression, because untreated psychological disturbance during pregnancy may persist into the postpartum period.


Termites of a South African savanna : I. List of species and subhabitat preferences.
This study describes the termite fauna of the South African Savanna Ecosystem Project study area at Nylsvley Reserve, Naboomspruit, northern Transvaal. Twenty species of fifteen genera and two families are recorded, and biological notes are given. The faunal composition is broadly similar to that of West African savannas, but a little impoverished. Main deficiencies are in variety of Macrotermitinae and Trinervitermes; Termitinae are broadly comparable.Most of the species occur in the flatter areas of broad-leaved savanna; three are restricted to open land bordering a marsh. Steeply rocky broad-leaved savanna lacks two species but has two others restricted to it; Acacia patches (including sites of former human settlement) have a much reduced variety of species.


A spectrophotometric method for the quantification of an enzyme activity producing 4-substituted phenols: determination of toluene-4-monooxygenase activity.
A spectrophotometric method for the quantitative determination of an enzyme activity resulting in the accumulation of 4-substituted phenols is described in this article. Toluene-4-monooxygenase (T4MO) activity in whole cells of Pseudomonas mendocina KR1 is used to demonstrate this method. This spectrophotometric assay is based on the coupling of T4MO activity with tyrosinase activity. The 4-substituted phenol, produced by the action of T4MO on the aromatic ring of a substituted arene, is a substrate for tyrosinase, which converts phenols to o-quinones. The latter react with the nucleophile 3-methyl-2-benzothiazolinone hydrazone (MBTH) to produce intensely colored products that absorb light maximally at different wavelengths, depending on the phenolic substrate used. The incubation of whole cells of P. mendocina KRI with fluorobenzene resulted in the accumulation of 4-fluorophenol. The coupling of T4MO activity with tyrosinase activity in the presence of fluorobenzene resulted in the formation of a colored product absorbing maximally at 480 nm. The molar absorptivity (epsilon) value for the o-quinone-MBTH adduct formed from 4-fluorophenol was determined experimentally to be 12,827 M(-1) cm(-1) with a linear range of quantification between 2.5 and 75 microM. The whole cell assay was run as a continuous indirect assay. The initial rates of T4MO activity toward fluorobenzene, as determined spectrophotometrically, were 61.8+/-4.4 nmol/min/mg P. mendocina KR1 protein (using mushroom tyrosinase), 64.9+/-4.6 nmol/min/mg P. mendocina KR1 protein (using cell extracts Pseudomonas putida F6), and, as determined by HPLC analysis, 62.6+/-1.4 nmol/min/mg P. mendocina KR1 protein.


Attention-based multimodal fusion with contrast for robust clinical prediction in the face of missing modalities.
With the increasing amount and growing variety of healthcare data, multimodal machine learning supporting integrated modeling of structured and unstructured data is an increasingly important tool for clinical machine learning tasks. However, it is non-trivial to manage the differences in dimensionality, volume, and temporal characteristics of data modalities in the context of a shared target task. Furthermore, patients can have substantial variations in the availability of data, while existing multimodal modeling methods typically assume data completeness and lack a mechanism to handle missing modalities. We propose a Transformer-based fusion model with modality-specific tokens that summarize the corresponding modalities to achieve effective cross-modal interaction accommodating missing modalities in the clinical context. The model is further refined by inter-modal, inter-sample contrastive learning to improve the representations for better predictive performance. We denote the model as Attention-based cRoss-MOdal fUsion with contRast (ARMOUR). We evaluate ARMOUR using two input modalities (structured measurements and unstructured text), six clinical prediction tasks, and two evaluation regimes, either including or excluding samples with missing modalities. Our model shows improved performances over unimodal or multimodal baselines in both evaluation regimes, including or excluding patients with missing modalities in the input. The contrastive learning improves the representation power and is shown to be essential for better results. The simple setup of modality-specific tokens enables ARMOUR to handle patients with missing modalities and allows comparison with existing unimodal benchmark results. We propose a multimodal model for robust clinical prediction to achieve improved performance while accommodating patients with missing modalities. This work could inspire future research to study the effective incorporation of multiple, more complex modalities of clinical data into a single model.


Mining Fatty Acid Biosynthesis for New Antimicrobials.
Antibiotic resistance is a serious public health concern, and new drugs are needed to ensure effective treatment of many bacterial infections. Bacterial type II fatty acid synthesis (FASII) is a vital aspect of bacterial physiology, not only for the formation of membranes but also to produce intermediates used in vitamin production. Nature has evolved a repertoire of antibiotics inhibiting different aspects of FASII, validating these enzymes as potential targets for new antibiotic discovery and development. However, significant obstacles have been encountered in the development of FASII antibiotics, and few FASII drugs have advanced beyond the discovery stage. Most bacteria are capable of assimilating exogenous fatty acids. In some cases they can dispense with FASII if fatty acids are present in the environment, making the prospects for identifying broad-spectrum drugs against FASII targets unlikely. Single-target, pathogen-specific FASII drugs appear the best option, but a major drawback to this approach is the rapid acquisition of resistance via target missense mutations. This complication can be mitigated during drug development by optimizing the compound design to reduce the potential impact of on-target missense mutations at an early stage in antibiotic discovery. The lessons learned from the difficulties in FASII drug discovery that have come to light over the last decade suggest that a refocused approach to designing FASII inhibitors has the potential to add to our arsenal of weapons to combat resistance to existing antibiotics.


The use of specific AAV serotypes to stably transduce primary CNS neuron cultures.
Although primary neuronal cell cultures are a valuable source of in vitro insight for many neurobiologists, all current gene expression technologies for these cells have significant drawbacks. Some of these limitations of current gene expression protocols include toxicity, transient expression, a requirement for postnatal neurons, and/or low efficiency. To date, many types of experiments were not possible because of these limitations. Here, we outline a methodology by which primary cultured neurons can be transduced at any age, after plating, with virtually no toxicity and continued gene expression for the lifetime of the culture. This method involves the use of adeno-associated viral vectors, which have the potential to be highly useful for either upregulation or downregulation of single or multiple genes, including neurotrophins, other neuroprotective genes, and neurotoxins.


In vitro assessment of anti-Leishmania immunity of man acquired with a vaccine.
Monocytes, obtained from a human volunteer immunized with a Leishmania infantum-derived vaccine, when cultured in vitro displayed a strong parasiticidal activity against L. major promastigotes. In addition, immune serum conferred leishmanicidal activities to monocytes of normal, unexposed donors, and to murine macrophages.


Acute effect of rheopheresis on peripheral endothelial dysfunction in patients suffering from sudden hearing loss.
Single low density lipoprotein (LDL) fibrinogen apheresis has shown beneficial effects in the treatment of patients with sudden sensorineural hearing loss (SSHL). Pathophysiologically, a microcirculatory disorder of the inner ear, probably caused by disturbed endothelial function, is discussed as a final common pathway of a variety of SSHL etiologies. Thus, we carried out a prospective pilot study on the efficacy of Rheopheresis on vascular function in these patients, embedded into an ongoing randomized controlled multicenter trial investigating the efficacy of Rheopheresis for the treatment of SSHL. Potential modulation of systemic endothelial dysfunction by Rheopheresis was examined by measuring flow-associated vasodilatation of the brachial artery (according to the criteria of the American College of Cardiology) in a small group of patients suffering from SSHL (N=6, 5m/1f, mean age 56+/-11 years) within the last 3 days. At baseline, five of the six patients with acute hearing loss showed endothelial dysfunction as evidenced by diminished flow-mediated vasodilatation (FMD<5%). After a single Rheopheresis treatment, flow-mediated vasodilatation improved significantly (from 3.9+/-3.6% to 7.2+/-2.4%, P=0.05, mean+/-SD, two-sided paired T-test). This was paralleled by a reduction in fibrinogen (364+/-216 mg/dL to 142+/-96 mg/dL, P=0.03), total cholesterol (228+/-23 to 98+/-10, P<0.0001) and LDL cholesterol levels (153+/-8 mg/dL to 83+/-23 mg/dL, P<0.01). Based on this case series we conclude that single Rheopheresis treatment might have an acute beneficial effect on endothelial dysfunction in patients suffering from SSHL.


Deep sequencing in library selection projects: what insight does it bring?
High throughput sequencing is poised to change all aspects of the way antibodies and other binders are discovered and engineered. Millions of available sequence reads provide an unprecedented sampling depth able to guide the design and construction of effective, high quality naïve libraries containing tens of billions of unique molecules. Furthermore, during selections, high throughput sequencing enables quantitative tracing of enriched clones and position-specific guidance to amino acid variation under positive selection during antibody engineering. Successful application of the technologies relies on specific PCR reagent design, correct sequencing platform selection, and effective use of computational tools and statistical measures to remove error, identify antibodies, estimate diversity, and extract signatures of selection from the clone down to individual structural positions. Here we review these considerations and discuss some of the remaining challenges to the widespread adoption of the technology.


Tissue polypeptide-specific antigen: a discriminative parameter between prostate cancer and benign prostatic hypertrophy.
The serum concentration of the cell proliferation marker TPS (tissue polypeptide-specific antigen) was compared with the tumour marker PSA (prostate specific antigen). PSA was found elevated in 50% of the benign prostatic hypertrophy (BPH) patients, in 88% of the patients with active prostate cancer and in 40% of the patients who were in an inactive phase. For TPS these values were 6, 34 and 0%, respectively. The metastatic progression was biochemically mirrored by pronounced elevations of PSA and TPS. These data suggest that TPS might be a valuable adjunct in the diagnosis and follow-up of patients with prostate cancer, especially in differentiating benign from malignant deterioration of the disease.


Synthetic oligonucleotides: AFM characterisation and electroanalytical studies.
One of the most important steps in designing more sensitive and stable DNA based biosensors is the immobilisation procedure of the nucleic acid probes on the transducer surface, while maintaining their conformational flexibility. MAC Mode AFM images in air demonstrated that the oligonucleotide sequences adsorb spontaneously on the electrode surface, showing the existence of pores in the adsorbed layer that reveal big parts of the electrode surface, which enables non-specific adsorption of other molecules on the uncovered areas. The electrostatic immobilisation onto a glassy carbon electrode followed by hybridisation with a complementary sequence and control with a non-complementary sequence was studied using differential pulse voltammetry and electrochemical impedance spectroscopy. Changes in the oxidation currents of guanosine and adenosine were observed after hybridisation events as well as after control experiments. Modification of the double layer capacitance that took place after hybridisation or control experiments showed that non-specific adsorption of complementary or non-complementary sequences occur allowing the formation of a mixed multilayer.


Some insights into analytical bias involved in the application of grab sampling for volatile organic compounds: a case study against used Tedlar bags.
In this study, we have examined the patterns of VOCs released from used Tedlar bags that were once used for the collection under strong source activities. In this way, we attempted to account for the possible bias associated with the repetitive use of Tedlar bags. To this end, we selected the bags that were never heated. All of these target bags were used in ambient temperature (typically at or below 30°C). These bags were also dealt carefully to avoid any mechanical abrasion. This study will provide the essential information regarding the interaction between VOCs and Tedlar bag materials as a potential source of bias in bag sampling approaches.


An Apela RNA-Containing Negative Feedback Loop Regulates p53-Mediated Apoptosis in Embryonic Stem Cells.
Maintaining genomic integrity is of paramount importance to embryonic stem cells (ESCs), as mutations are readily propagated to daughter cells. ESCs display hypersensitivity to DNA damage-induced apoptosis (DIA) to prevent such propagation, although the molecular mechanisms underlying this apoptotic response are unclear. Here, we report that the regulatory RNA Apela positively regulates p53-mediated DIA. Apela is highly expressed in mouse ESCs and is repressed by p53 activation, and Apela depletion compromises p53-dependent DIA. Although Apela contains a coding region, this coding ability is dispensable for Apela's role in p53-mediated DIA. Instead, Apela functions as a regulatory RNA and interacts with hnRNPL, which prevents the mitochondrial localization and activation of p53. Together, these results describe a tri-element negative feedback loop composed of p53, Apela, and hnRNPL that regulates p53-mediated DIA, and they further demonstrate that regulatory RNAs add a layer of complexity to the apoptotic response of ESCs after DNA damage.


Nerve disorders in dancers.
Dancers are required to perform at the extreme of physiologic and functional limits. Under such conditions, peripheral nerves are prone to compression. Entrapment neuropathies in dance can be related to the sciatic nerve or from a radiculopathy related to posture or a hyperlordosis. The most reproducible and reliable method of diagnosis is a careful history and clinical examination. This article reviews several nerve disorders encountered in dancers, including interdigital neuromas, tarsal tunnel syndrome, medial hallucal nerve compression, anterior tarsal tunnel syndrome, superficial and deep peroneal nerve entrapment, and sural nerve entrapment.


The influence of early virtual reality intervention on pain, anxiety, and function following primary total knee arthroplasty.
Total knee arthroplasty (TKA) is one of the most popular surgeries in the orthopedic field. One of the reasons for a failed TKA is pain and difficulty to return to normal function. A pain control method that is becoming more and more popular is the use of virtual reality (VR). We aimed to examine VR intervention in the immediate post-operative physiotherapy following TKA. This prospective randomized-controlled study recruited a total of 55 patients undergoing primary TKA in a single institute, operated by three surgeons. They were assigned either study group or control group. Both groups were treated with conventional physiotherapy and CPM equipment (Continuous passive motion device), the study group received additional VR modality. Both groups completed a series of questionnaires prior and after the intervention: State-Trait Anxiety Inventory (STAI) questionnaire (used to diagnose anxiety), Visual analog scale (VAS) for pain and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) (knee function score). The average age was 70 years-old with equal distribution of male and female. Both groups showed a decrease in pain and anxiety following the intervention (p value < 0.05) but there was no difference between the groups (p value > 0.05 for all parameters). The was no difference in the WOMAC scores in the six-month post-operative examination between groups (p-value = 0.653). Virtual reality intervention in the immediate post-operative period following total knee arthroplasty decrease pain and anxiety but did not influence the pain, anxiety, and long-term function results more than conventional physiotherapy.


HPV16-E7 expression causes fluorodeoxyuridine-mediated radiosensitization in SW620 human colon cancer cells.
We have reported that HT29 colon cancer cells, which are radiosensitized by fluorodeoxyuridine (FdUrd), exhibit a greater increase in cyclin E-dependent kinase activity and progress further into S phase in the presence of FdUrd than do SW620 colon cancer cells, which are only minimally sensitized by this drug (Cancer Res 56: 3203, 1996). Although these findings suggested that the ability to progress into S phase in the presence of FdUrd permits cells to be radiosensitized, we wished to test this hypothesis by attempting to drive SW620 human colon cells into S phase by transducing them with the HPV16-E7 gene. Two-parameter flow cytometry showed that E7-transduced cells progressed through S phase after radiation and FdUrd treatment more rapidly than SW620 parental cells. We found that E7-transduced SW620 cells were significantly radiosensitized by FdUrd (100 nmol/L, 14 hours) with an enhancement ratio for 2 clones of 1.47 +/- 0.03 and 1.51 +/- 0.14, compared with 1.24 +/- 0.04 in SW620 parental cells. These data strongly support the hypothesis that dysregulation of S-phase progression is an important factor in FdUrd-mediated radiosensitization.


Urethral sensitivity in the aetiology of sensory urgency.
To investigate urethral hypersensitivity as a cause of sensory urgency. Twenty women with sensory urgency and 10 normal controls were enrolled in the study. A urethral conductance catheter was designed comprising three pairs of electrodes. These were accurately located in the urethra using the principle of urethral electrical conductance. The urethral sensory threshold was then measured at three sites along the urethral by applying a stimulatory current across each pair of electrodes in turn. The women with sensory urgency had significantly higher thresholds for urethral stimulation along the whole urethra when compared with the control group. Urethral hypersensitivity was not found to be a feature of sensory urgency and in fact the converse was demonstrated. This has not been described before. High sensory thresholds may occur with small fibre peripheral neuropathies. Thus, peripheral neuropathy is potentially a factor in the, as yet unknown, aetiology of sensory urgency.


Engineering 4-coumaroyl-CoA derived polyketide production in Yarrowia lipolytica through a β-oxidation mediated strategy.
Polyketides are a diverse class of molecules sought after for their valuable properties, including as potential pharmaceuticals. Previously, we demonstrated that the oleaginous yeast Yarrowia lipolytica is an optimal host for production of the simple polyketide, triacetic acid lactone (TAL). We here expand the capacities of this host by overcoming previous media challenges and enabling production of more complex polyketides. Specifically, we employ a β-oxidation related strategy to improve polyketide production directly from defined media. Beyond TAL production, we establish biosynthesis of the 4-coumaroyl-CoA derived polyketides: naringenin, resveratrol, and bisdemethoxycurcumin, as well as the diketide intermediate, (E)-5-(4-hydroxyphenyl)-3-oxopent-4-enoic acid. In this background, we enable high-level de novo production of naringenin through import of both a heterologous pathway and a mutant Y. lipolytica allele. In doing so, we generated an averaged maximum titer of 898 mg/L naringenin, the highest titer reported to date in any host. These results demonstrate that Y. lipolytica is an ideal polyketide production host for more complex 4-coumaroyl-CoA derived products.


Donor Immunization Against Human Leukocyte Class II Antigens is a Risk Factor for Graft-versus-Host Disease.
The sensitization to HLA antigens is caused mainly by pregnancy and transfusions; however, anti-HLA antibodies also may be detected in nulliparous females and nontransfused males, and thus specifically in hematopoietic stem cell transplantation (HSCT) donors. In such cases, the impact on HSCT outcome is known only for platelet transfusion refractoriness. This study addresses the impact on graft-versus-host disease (GVHD) of anti-HLA antibodies detected in voluntary unrelated donors. Among 100 donor/recipient (D/R) pairs, 33 and 82 showed at least 1 HLA class I and class II mismatch, respectively. Because class II mismatches were more frequent, we focused our detection on anti-class II antibodies, using the Luminex assay. Among 82 HLA class II mismatched D/R pairs, 26 donors (32%) had at least 1 anti-HLA class II antibody detected in peripheral blood. Recipients of a graft from an anti-class II immunized donor had a higher cumulative incidence for a first episode of either acute or chronic GVHD (2- year cumulative incidence, 88% versus 67%; P = .03), which was confirmed in multivariate analysis (hazard ratio, 1.7; P = .04). In particular, according to the National Institutes of Health classification scheme, the cumulative incidence of chronic GVHD was higher in recipients of immunized donors (multivariate hazard ratio, 2.5; P = .02). Identifying specificities of anti-class II antibodies revealed that 13 of 26 alloimmunized donors had recipient-specific antibodies, directed mainly against mismatched HLA-DPB1 alleles. Donor-derived anti-HLA antibodies could be detected in recipients up to at least 6 months post-HSCT, supporting their association with chronic GVHD. Donor immunization against foreign HLA antigens is a new parameter to predict the occurrence of GVHD after HSCT from HLA-mismatched unrelated donors.


Boosting Alkaline Hydrogen Evolution Reaction through Water Structure Manipulation.
In the past, the design of efficient electrocatalyst materials for alkaline hydrogen evolution reaction (HER) was mostly focused on tuning the adsorption properties of reaction intermediates. A recent breakthrough shows that the performance can be improved by manipulating water structure at the electrode-electrolyte interface using atomically localized electric fields. The new approach was realized by using IrRu dizygotic single-atom sites and led to a significantly accelerated water dissociation and an overall improved alkaline HER performance. Supported by extensive data from advanced modeling, characterization, and electrochemical measurements, the work delivers an intricate examination of the interaction between water molecules and the catalyst surface, thereby enriching our understanding of water dissociation kinetics and offering new insights to boost overall alkaline HER efficiency.


Triclocarban affects earthworms during long-term exposure: Behavior, cytotoxicity, oxidative stress and genotoxicity assessments.
Triclocarban (TCC) is a contaminant of emerging concern widely applied as an antimicrobial in personal care products and introduced into the terrestrial environment through the application of biosolids (i.e., treated sewage sludge) in agriculture. Displaying the potential to bioaccumulate in the food chain and a high half-life in the soil, the presence of this compound in the environment may lead to potential ecological risks. In this context, TCC toxicity assessments in Eisenia andrei earthworms were carried out through acute, avoidance and chronic tests following cytotoxicity, antioxidant system, i.e. acatalase (CAT), glutathione-S-transferase (GST), glutathione (GSH), lipid peroxidation (LPO), and DNA damage (comet assay) evaluations. An LC50 of 3.3 ± 1.6 mg cm-2 in the acute contact test and an EC50 of 1.92 ± 0.31 mg kg-1 in the avoidance test during 72 h and 48 h, respectively, were obtained. The behavioral test indicates earthworm avoidance from 15.0 mg kg-1 of TCC. During chronic soil exposure, a 44% reduction in earthworm cell viability was observed after 14 days of exposure to 10 mg kg-1 TCC, while an increase in the percentage of amoebocyte cells also ocurred. Chronic exposure to TCC led to reduced CAT and GST activities, decreased GSH levels and increased LPO in exposed organisms. DNA damage was observed after 45 days from a 1 mg kg-1 dose of TCC. Therefore, TCC exhibits toxicological potential to Eisenia andrei earthworms, mainly during long-term exposures. This study provides mechanistic earthworm information towards understanding the environmental and human health implications of TCC exposure and draws attention to correct biosolid management.


Olfactory dysfunction revisited: a reappraisal of work-related olfactory dysfunction caused by chemicals.
Occupational exposure to numerous individual chemicals has been associated with olfactory dysfunction, mainly in individual case descriptions. Comprehensive epidemiological investigations into the olfactotoxic effect of working substances show that the human sense of smell may be impaired by exposure to metal compounds involving cadmium, chromium and nickel, and to formaldehyde. This conclusion is supported by the results of animal experiments. The level of evidence for a relationship between olfactory dysfunction and workplace exposure to other substances is relatively weak.


Independent and combined associations of dietary antioxidant intake with bone mineral density and risk of osteoporosis among elderly population in United States.
The influence of dietary antioxidant intake on the occurrence and progression of osteoporosis may be significant. However, to date, evidence on the link between combined effect of dietary antioxidants on bone mineral density (BMD) level and risk of osteoporosis is limited. We aimed to assess the independent and combined association of dietary antioxidant intake with BMD level and risk of osteoporosis among elderly population in United States through analysis of data in the National Health and Nutrition Examination Survey. The dietary antioxidant intake was assessed based on six antioxidants, including vitamin A, vitamin C, vitamin E, zinc, selenium, and total carotenoid. A composite dietary antioxidant index (CDAI) was used to evaluate the combined exposure of dietary antioxidant intake. A total of 5618 participants were included. Higher dietary vitamin A, vitamin C, vitamin E, zinc, selenium, and total carotenoid, were positively associated with BMD level. Compared with participants in the first quartile, those in the higher quartile of vitamin E (Q4: OR 0.652; 95% CI 0.463-0.918), zinc (Q4: OR 0.581; 95% CI 0.408-0.826), and selenium (Q3: OR 0.673; 95% CI 0.503-0.899) were associated with decreased risk of overall osteoporosis. Furthermore, compared to those in the first quartile, participants in the highest quartile of CDAI were associated with increased total femur (β 0.019; 95% CI 0.007-0.032), femur neck (β 0.020; 95% CI 0.009-0.032), trochanter (β 0.012; 95% CI 0.001-0.023), and intertrochanter BMD level (β 0.022; 95% CI 0.007-0.037); participants in the highest quartile of CDAI were associated with decreased risk of overall osteoporosis (OR 0.536; 95% CI 0.376-0.763). Furthermore, the associations of CDAI with the BMD level and osteoporosis risk were more significant among female participants. Our study provides evidence that a combination of dietary antioxidants intake was associated increased BMD level and decreased osteoporosis risk.


Serum elafin as a potential inflammatory marker in psoriasis.
Psoriasis is a distressing chronic skin disease. Its exact pathogenesis is still unclear, as many factors interplay in its occurrence. The aim of the study is to estimate elafin levels in the serum of both cases and controls and to correlate the levels with psoriasis severity and other markers of inflammation. Twenty-six psoriatic cases along with 26 healthy controls were assigned in this case-control study. Psoriasis severity was determined by Psoriasis Area and Severity Index score. Elafin levels were measured by ELISA in serum of both cases and controls. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured in the cases. Elafin levels show highly statistical significance difference (P < 0.001) between cases and controls. There is a statistical significant correlation between elafin levels and both psoriasis severity and inflammation markers as CRP and ESR. Elafin represents a mirror for psoriasis severity and inflammatory state.


The DNA damage potential of quantum dots: Toxicity, mechanism and challenge.
Quantum dots (QDs) are semiconductor nanoparticles (1-10 nm) with excellent optical and electrical properties. As QDs show great promise for applications in fields such as biomedicine, their biosafety is widely emphasized. Therefore, studies on the potential 'nanotoxicity' of QDs in genetic material are warranted. This review summarizes and discusses recent reports derived from different cell lines or animal models concerning the effects of QDs on genetic material. QDs could induce many types of genetic material damage, which subsequently triggers a series of cellular adverse outcomes, including apoptosis, cell cycle arrest and senescence. However, the individual biological and ecological significance of the genotoxicity of QDs is not yet clear. In terms of mechanisms of genotoxicity, QDs can damage DNA either through their own nanomorphology or through the released metal ions. It also includes the reactive oxygen species generation, inflammation and failure of DNA damage repair. Notably, apoptosis may lead to false positive results in genotoxicity tests. Finally, given the different uses of QDs and the interference of the physicochemical properties of QDs on the test method, genotoxicity testing of QDs should be different from traditional toxic compounds, which requires further research.


Autologous blood injection for treatment of chronic recurrent TMJ dislocation: is it successful? Is it safe enough? A systematic review.
The purpose of this article is to review the English literature about the efficacy and safety of autologous blood injection in treating patients suffering from chronic recurrent temporomandibular joint dislocation. In this article, we highlight the key trials and recent directions about this modality and discuss about the mechanism, advantages, and disadvantages of this approach. A literature search was performed using PubMed, Medline, and Ovid Medline databases to identify articles reporting on the injection of autologous blood for treatment of chronic recurrent dislocation of temporomandibular joint. Other references cited in the retrieved reports, as well as the "related articles" tool in PubMed Medline, were also checked to improve the search and, if relevant, were included in the study. The search was restricted to articles published in the English language. Seven studies meeting the inclusion criteria were reviewed. The selected articles included four prospective clinical trials and three case report articles. There are a few articles about the clinical use of autologous blood for treating patients with chronic recurrent temporomandibular joint dislocation. Reviewing of the literature shows that there are successful results about this modality, but there are still some concerns about it in terms of the effect of the injected blood on the articular cartilage and formation of fibrous or bony ankylosis.


Association between neurite metrics and tau/inflammatory pathology in Alzheimer's disease.
The molecular mechanism of neurodegeneration, including tau and neurite complexity, is an important topic in Alzheimer's disease (AD) research. We recruited 27 amyloid-positive individuals identified through 11C-Pittsburgh compound B (PiB) positron emission tomography (PET) and 31 amyloid-negative individuals with normal cognition. All participants underwent 11C-PiB and 18F-THK5351 PET and magnetic resonance imaging (MRI) with neurite orientation dispersion and density imaging (NODDI) protocol. The neurite density index (NDI), orientation dispersion index (ODI), and PET images were analyzed to calculate voxel-wise correlations among the imaging modalities and correlations with cognitions. In the amyloid-positive participants, there were significant negative correlations between 18F-THK5351 and NDI and between 18F-THK5351 and ODI. The bilateral mesial and lateral temporal lobes were mainly involved. Regarding cognition, 18F-THK5351 showed more marked associations with all cognitive domains than the other modalities. Tau and neuroinflammation in AD may reduce the neurite density and orientation dispersion, particularly in the mesial and lateral temporal lobes.


Anticancer and anti-angiogenic activities of extract from Actinidia eriantha Benth root.
The roots of Actinidia eriantha Benth (AER) are commonly used traditional folk medicine for the treatment of gastric carcinoma, nasopharyngeal carcinoma, and breast carcinoma. Besides, the anti-proliferative and immunomodulatory effects of AER polysaccharides on tumor-bearing mice have been reported previously. This work was carried out to investigate the anticancer and anti-angiogenic activities of AER. The growth inhibitory effects of ethanol extracts from the leaves (EEL), stems (EES) and roots (EER) of A. eriantha on human gastric carcinoma SGC7901 cells, human nasopharyngeal carcinoma CNE2 cells, human breast carcinoma MCF7 cells and human umbilical vein endothelial cells (HUVECs) were evaluated by MTT assay. The ethyl acetate fraction from EER (EA-EER) was further investigated for the anticancer activity against SGC7901 cells and the anti-angiogenic activity in HUVECs in vitro. The apoptosis in SGC7901 cells and HUVECs was confirmed by DAPI nuclear staining and flow cytometry analysis, the effect on cellular DNA fragmentation was detected in SGC7901 cells. And the cell cycle-arresting activity in HUVECs was determined by flow cytometry. Moreover, the inhibitory effect of EA-EER on cell migration in HUVECs was observed by both wound-healing and Transwell migration assays. RT-PCR and Western-blotting were performed to determine the mRNA and protein expression levels, respectively, including Bax, Bcl-2 and caspase-3 in SGC7901 cells, as well as VEGF-A and VEGFR-2 in HUVECs. Furthermore, the in vivo anti-angiogenic activity of EA-EER was evaluated by using chick embryo chorioallantoic membrane (CAM) assay. Ultimately, the chemical components in EA-EER were isolated and purified by repeated column chromatography followed by structure characterization using 1H and 13C nuclear magnetic resonance and mass spectroscopy. Compared with EEL and EES, EER displayed the strongest growth inhibitory effect on SGC7901 cells, CNE2 cells and HUVECs. Among the EER fractions, EA-EER exhibited the most potent growth inhibitory activity against SGC7901 cells, CNE2 cells and HUVECs. Moreover, EA-EER induced obvious apoptosis in SGC7901 and HUVECs, and significantly inhibited the proliferation of HUVECs via blockade of cell cycle G1 to S progression. Furthermore, EA-EER suppressed the expression of Bcl-2 and improved the expression Bax and caspase-3 in SGC7901 cells. EA-EER not only inhibited migration of HUVECs, but also down-regulated the expression of VEGF-A and VEGFR-2 in HUVECs. In vivo, EA-EER exposure reduced the formation of blood vessels in chick embryos. A bio-guided isolation of EA-EER led to the isolation of three compounds for the first time, namely (6R, 7E, 9S)-6, 9-hydroxy-megastigman-4, 7-dien-3-one-9-O-β-D-glucopyranoside, Oleanolic acid-23-O-β-D-glucopyranoside, 3β, 23, 24-trihydroxyl-12-oleanen-28-oic acid. The present research demonstrated that the significant anticancer and anti-angiogenic effects of AER, providing the supportive evidence for its traditional use in the treatment for cancer. It was suggested that AER could be use as a potential source of cancer therapeutic drug.


Triple burden of malnutrition among mother-child pairs in low-income and middle-income countries: a cross-sectional study.
This study aimed to assess the prevalence and determinants of the triple burden of malnutrition among mother-child pairs in low-income and middle-income countries. Cross-sectional study. Low-income and middle-income countries. Women and children. Triple burden of malnutrition (overweight/obese mother with undernourished and anaemic under 5 years child). Data for this study were drawn from recent 22 low-income and middle-income countries Demographic and Health Surveys. A total weighted sample of 116 795 mother-child pairs was included in the study. STATA V.14.2 was used to clean, code and analyse the data. Multilevel logistic regression was employed to identify factors associated with the problem. Adjusted OR (AOR) with 95% CI and a p<0.05 was reported to indicate statistical association. Model fitness and comparison were done using intraclass correlation coefficient, median OR, proportional change in variance and deviance. The pooled prevalence of the triple burden of malnutrition among mother-child pairs was 11.39%. It showed statistically significant positive associations with mothers aged ≥35 years (AOR 2.25, 95% CI 2.08 to 2.44), family size >10 (AOR 1.17, 95% CI 1.08 to 1.26), delivery by caesarean section (AOR 1.93, 95% CI 1.83 to 2.03), the richest household (AOR 1.72, 95% CI 1.56 to 1.88), grand multiparous (AOR 1.62, 95% CI 1.46 to 1.81), age of child 36-47 months (AOR 1.77, 95% CI 1.64 to 1.90), at a p<0.05. Whereas breast feeding (AOR 0.94, 95% CI 0.89 to 0.99), married mothers (AOR 0.87, 95% CI 0.78 to 0.96), female children (AOR 0.88, 95% CI 0.84 to 0.92), improved toilet (AOR 0.23, 95% CI 0.17 to 0.29), improved source of drinking water (AOR 0.28, 95% CI 0.21 to 0.35), rural residents (AOR 0.66, 95% CI 0.62 to 0.69) had a contrasting relationship with the triple burden of malnutrition. About 1 out of 10 households suffer from the triple burden of malnutrition in low-income and middle-income countries. This study revealed that several maternal, child, household and community-level factors have a significant impact on the triple burden of malnutrition among mother-child pairs.


Pharmacokinetic enhancers (cobicistat/ritonavir) and the potential for drug-drug interactions.
The potential for clinically significant drug interactions (CSDIs) for patients taking ritonavir and cobicistat is high because of their powerful pharmacokinetic effect on the cytochrome P450 (CYP) enzyme system, most notably their inhibitory effect on CYP3A4. An audit was conducted to measure and correct for patients exposed to potentially dangerous drug interactions. Two hundred individuals attending a regional specialist human immunodeficiency virus (HIV) clinic between June and September 2014 who were receiving the pharmacokinetic enhancers ritonavir or cobicistat were interviewed to determine a medication history including medications prescribed by their general practitioner (GP), over-the-counter (OTC) medicines, herbal remedies and recreational drugs. Of the 200 patients interviewed, patients were aged 23-76 years (median age was 41.5), 64% were female and 173 reported taking a co-medication. Sixty-six (33%) were taking a medication or medications which had no significant drug interaction associated with them. One hundred and seven (54%) were taking one or more medications with a CSDI which could require a dose adjustment, close monitoring or an absolute contraindication. Only 27% of these co-medications were identified in the normal course of an outpatient visit outside of the audit. A detailed medication history is often lacking at routine HIV follow-up visits. There is a significant risk of CSDIs in this cohort. Awareness of physicians and pharmacists needs to be raised. Implementation of several innovative strategies to capture the most accurate medication histories and avoid drug toxicities now employed in this cohort is also discussed here.


The use of nonnutritive sucking to facilitate oral feeding in a term infant: a single case study.
This individual case study presents an evaluation of and reflection on the use of nonnutritive sucking as a technique to facilitate nutritive sucking with an infant with feeding difficulties. Nonnutritive sucking is used in a variable way with mainly premature or sick infants. However, the rationale underpinning use of such an approach is not clear. The infant participant in this study, Baby H, was born at 37 weeks. This case illustrates the use of nonnutritive sucking as an approach with supported rationales for promoting transition toward oral feeding with infants who have complex needs and who are term infants. The literature focuses on using nonnutritive sucking with premature infants who have no additional difficulties such as hypoxic neonatal encephalopathy, meconium aspiration, sepsis, or severe perinatal asphyxia. The intervention carried out with Baby H demonstrates that nonnutritive sucking can contribute toward the management of an infant's feeding development. Baby H took 23 days to develop a sequential nonnutritive sucking pattern, but her ability to transfer this to nutritive sucking and safe feeding took the first 17 months of this infant's life. This study is unique in that it explored the issues involved with a term infant who had complex needs that impacted on feeding development. It is important because many practitioners use nonnutritive sucking with infants who have complex needs.


Evaluation of preemptive effect of epidural S(+)-ketamine for hysterectomy: plasmatic concentrations of interleukins.
Some studies showed that ketamine inhibits the production of cytokines. The objective of this study was to evaluate the preemptive analgesic effect of epidural S(+)-ketamine in hysterectomy and plasmatic cytokines (IL-6, TNF-α and IL-10). A double-blinded study with 29 patients was conducted. Patients in Group 1 received 13 mL of 0.25% bupivacaine with 25mg of S(+)- ketamine 30 minutes before surgical incision and 15 mL of saline solution via the epidural route 30 minutes after. Patients in Group 2 received 15 mL of saline solution 30 minutes before the surgical incision, followed by 13 mL of 0.25% bupivacaine with 25mg of S(+)-ketamine 30 minutes after. Postoperative analgesia was made with epidural bupivacaine and fentanyl. Dipyrone 1 g was used whenever required. The following paramenters were evaluated: concentration of cytokines, intensity of pain, time of first request of analgesic and total quantity of analgesic used. Time for the first request for analgesics was 61.5 minutes in Group 1 and 69.0 in Group 2, without difference between these groups. There was no difference for total dose of fentanyl used in Group 1 (221.4 μg) and Group 2 (223.3 μg). A similar analgesic effect was obtained in both groups, except in T12 (Group 1 = 2.4±3.2; Group 2 = 5.5±3.4). No differences in concentration of cytokines were observed. The epidural injection of 25mg S(+)-ketamine before incision reduced the pain intensity only 12 hours after surgical incision and did not alter concentration of cytokines.


Performance of threshold-based stone segmentation and radiomics for determining the composition of kidney stones from single-energy CT.
Knowledge of kidney stone composition can help in patient management; urine composition analysis and dual-energy CT are frequently used to assess stone type. We assessed if threshold-based stone segmentation and radiomics can determine the composition of kidney stones from single-energy, non-contrast abdomen-pelvis CT. With IRB approval, we identified 218 consecutive patients (mean age 64 ± 13 years; male:female 138:80) with the presence of kidney stones on non-contrast, abdomen-pelvis CT and surgical or biochemical proof of their stone composition. CT examinations were performed on one of the seven multidetector-row scanners from four vendors (GE, Philips, Siemens, Toshiba). Deidentified CT images were processed with a radiomics prototype (Frontier, Siemens Healthineers) to segment the entire kidney volumes with an AI-based organ segmentation tool. We applied a threshold of 130 HU to isolate stones in the segmented kidneys and to estimate radiomics over the segmented stone volume. A coinvestigator verified kidney stone segmentation and adjusted the volume of interest to include the entire stone volume when necessary. We applied multiple logistic regression tests with precision recall plots to obtain area under the curve (AUC) using a built-in R statistical program. The threshold-based stone segmentation successfully isolated kidney stones (uric acid: n = 102 patients, calcium oxalate/phosphate: n = 116 patients) in all patients. Radiomics differentiated between calcium and uric acid stones with an AUC of 0.78 (p < 0.01, 95% CI 0.73-0.83), 0.79 sensitivity, and 0.90 specificity regardless of CT vendors (GE CT: AUC = 0.82, p < 0.01, 95% CI 0.740-0896; Siemens CT: AUC = 0.77, 95% CI 0.700-0.846, p < 0.01). Automated threshold-based stone segmentation and radiomics can differentiate between calcium oxalate/phosphate and urate stones from non-contrast, single-energy abdomen CT.


Long non-coding RNA AC245100.4 activates the PI3K/AKT pathway to promote PCa cell proliferation by elevating PAR2.
Prostate cancer (PCa) is among the most generally diagnosed cancers in males. A long non-coding RNA (lncRNA) called AC245100.4 has been discovered and linked to PCa carcinogenesis. However, its specific and potential mechanism is uncertain in PCa. In this research, we investigated the role of AC245100.4 in cell proliferation and the underlying mechanism in PCa cells. qRT-PCR assays were utilized to detect AC245100.4 expression and confirm its downstream target. The pathways related to AC245100.4 were identified by RAP-MS. PCa cell proliferation was experimented by Cell Counting Kit-8 and Colony formation assays. Western blot was performed to detect PAR2, AKT, p-AKT, Cyclin D1 and PCNA expression. AC245100.4/PAR2 overexpression promotes PCa cell proliferation and the opposite results are obtained after AC245100.4/PAR2 knockdown. Mechanistically, we found that PAR2 is confirmed as the AC245100.4 downstream target and AC245100.4 promotes PCa cell proliferation by regulating PAR2. AC245100.4 promotes PCa cell proliferation via PI3K/AKT pathway. Rescue assays validated that PAR2 knockdown reversed the impact of AC245100.4 overexpression on increasing p-AKT protein levels. This research revealed that AC245100.4 enhances cell proliferation in PCa cells through modulating the PAR2/PI3K/AKT axis, which may offer novel tumor markers and potential therapeutic targets for PCa.


Plasma concentrations and hemodynamic effects of nifedipine: a study in anesthetized dogs.
The elimination kinetics of the calcium channel blocking agent nifedipine were studied in three male mongrel dogs after single intravenous bolus doses, and the drug's disposition followed first-order kinetics. After single intravenous doses, the elimination rate constant (mean +/- SE) was 0.693 +/- 0.069 h-1; the total body clearance, 0.736 +/- 0.226 L/h/kg; and the apparent volume of distribution, 1.15 +/- 0.12 L/kg. Based on these data, a model for the administration of nifedipine by an intravenous bolus-infusion regimen was developed to rapidly achieve and maintain stable plasma drug concentrations. Testing of this model in six anesthetized, open-chest dogs revealed pulmonary artery (mixed venous) drug concentrations that were consistently lower than those predicted, with stable plasma nifedipine levels achieved within 5 min and maintained over 60-min study periods. In these animals, a linear relationship was found between nifedipine concentrations in plasma and the total amount of drug administered (r = 0.92, p less than 0.001). Log-linear relationships were found between plasma nifedipine concentrations and mean arterial blood pressure (r = -0.93, p less than 0.001), cardiac output (r = 0.94, p less than 0.001), peripheral vascular resistance (r = -0.93, p less than 0.001), and pulmonary vascular resistance (r = -0.83, p less than 0.001). In addition, infusion of CaCl2 (3 mg/kg/min) resulted in increases in blood pressure despite the presence of stable plasma nifedipine concentrations. No electrocardiographic changes were seen at any plasma nifedipine level.


Impact of the interpregnancy interval after cesarean delivery on subsequent perinatal risks: a retrospective study.
To assess the impact of the interpregnancy interval (IPI) after cesarean delivery on the risks of adverse perinatal events during subsequent pregnancies. We retrospectively examined perinatal outcomes of subsequent pregnancies of women whose most recent birth experience involved cesarean delivery at our hospital between January 2014 and December 2019. IPI was defined as the time between live birth and subsequent conception. Three IPI groups: < 18 months, 18-60 months, and > 60 months, were assessed. The risks of preterm birth, preeclampsia, placenta previa, placental abruption, fetal growth restriction, and successful vaginal birth were compared among the three IPI groups using uni- and multivariate analyses. We registered 592 births after cesarean delivery: 178, 288, and 126 in the IPI < 18 months, 18-60 months, and > 60 months groups, respectively. The groups did not differ significantly regarding perinatal outcomes. The multivariate analysis revealed no significant differences in the risks of adverse perinatal outcomes among all groups. The odds ratios (ORs) for preterm birth at < 37 weeks of gestation were 1.24 and 1.64 for those in the < 18 months and > 60 months groups, respectively (P = 0.362 and P = 0.055, respectively). The groups did not differ significantly regarding vaginal birth success rate (ORs 1.72 for the < 18 months group, 0.49 for the > 60 months group; P = 0.486 and P = 0.446, respectively). After cesarean delivery, IPIs shorter than 18 months and longer than 60 months do not significantly impact the risks of adverse perinatal outcomes or successful vaginal birth compared with IPIs of 18-60 months.


STIM and calcium channel complexes in cancer.
The ion Ca(2+) is a ubiquitous second messenger that mediates a variety of cellular functions. Dysfunction of the mechanisms involved in Ca(2+) homeostasis underlies a number of pathological processes, including cancer. Store-operated Ca(2+) entry (SOCE) is a major mechanism for Ca(2+) entry modulated by the intracellular Ca(2+) stores. The Ca(2+)-selective store-operated current (ICRAC) is mediated by the endoplasmic reticulum (ER) Ca(2+) sensor STIM1 and the store-operated Ca(2+) (SOC) channel Orai1, while other non-selective cation currents (ISOC) involves the participation of members of the canonical transient receptor potential (TRPC) channel family, including TRPC1. Distinct isoforms of the key components of SOCE have been described in mammalian cells, STIM1 and 2, Orai1-3 and TRPC1-7. In cancer cells, SOCE has been reported to play an important role in cell cycle progression and proliferation, migration, metastasis and evasion of apoptosis. Changes in the expression of the key elements of SOCE and Ca(2+) homeostasis remodeling have been account to play important roles in the phenotypic changes observed in transformed cells. Despite there are differences in the expression level of the molecular components of SOCE, as well as in the relevance of the STIM, Orai and TRPC isoforms in SOCE and tumorigenesis among cancer cell types, there is a body of evidence supporting an important role for SOCE underlying the phenotypic modifications of cancer cells that propose STIM and the SOC channels as suitable candidate targets for future prognostic or therapeutic strategies. This article is part of a Special Issue entitled: Calcium and Cell Fate. Guest Editors: Jacques Haiech, Claus Heizmann, Joachim Krebs, Thierry Capiod and Olivier Mignen.


Effect of replacing corn straw by sweet sorghum silage or whole plant corn silage in sheep diets on rumen fermentation and bacterial flora.
Sweet sorghum silage (SS; Sorghum dochna 'Dochna') has been extensively studied in recent years as a supplementary forage-to-corn silage (CS; Zea mays L.), but there are still relatively few studies on its effects on the rumen environment of sheep. Determining the short-term impact of converting roughage from corn straws to SS compared to CS on rumen fermentation and bacterial population dynamics was the main goal of the current study. Twelve female thin-tailed Han sheep (29.8 ± 1.34 kg) were randomly divided into one of two treatments: concentrate supplemented with SS or CS, respectively. During the 15-day pretest period, concentrate was fed in two separate feedings at 0800 h and 1800 h, and ensure that the animals were all consumed within an hour of being fed. Thereafter, the animals had free access to corn straw. The feeding procedures during the pretest period were the same as during the measurement period. Rumen fluid was collected via sheep esophageal tube on the last day of adaptation phase (1-7 days) and stabilisation phase (8-30 days), respectively. The results showed that there was a similarity in the total concentration of VFA (volatile fatty acid) and the proportions of acetate, propionate, butyrate, and branched-chain VFA (P > 0.05) and microbial diversity indices (P > 0.05) between the two silage groups throughout the experimental period. The concentration of Ammonia nitrogen (P = 0.001) and proportion of valerate (P = 0.028) decreased in the CS and SS groups, respectively. The abundance and predicted function of rumen bacteria in the SS group did not differ significantly (P > 0.05) between the two measurement phases. However, the abundance of Prevotella_1 (P = 0.038) was higher in the CS group than in the SS group at 7 d. The abundances of Firmicutes (P = 0.005) and Ruminococcaceae_NK4A214_group (P = 0.002) increased, while the abundances of Bacteroidetes (P = 0.044), Proteobacteria (P = 0.046), and Prevotella_1 (P = 0.009) decreased in the CS group at 30 d. Genes related to pyruvate metabolism (P = 0.020) were significantly higher at 30 d than at 7 d, whereas purine metabolism (P = 0.007), pyrimidine metabolism (P = 0.007), and metabolic pathways (P = 0.010) were lower at 30 d in the CS group. In conclusion, this study indicated that SS maintained a steady rumen environment, while CS caused high fluctuations in bacterial abundance and predicted function for sheep.


Optimization of an aqueous tablet-coating process containing carboxymethylated Cassia fistula gum.
The present investigation was aimed at developing and optimizing a simple aqueous tablet-coating formulation and its process. 5-Fluorouracil (5-FU) was used to ascertain the relative lipophilic/hydrophilic behavior of the coating system. Optimization was performed by evaluating the adhesive force strength and cohesive force strength of the tablet coat using a texture analyzer. The in vitro release of 5-FU was found to decrease with an increase in (tablet surface-coat) adhesive force strength. The (tablet-tablet) cohesive force strength was reduced by the addition of magnesium silicate to the coating solution. The addition of magnesium silicate (0.2% w/v) to the carboxymethyl Cassia fistula gum-chitosan (CCG-CH) coating surface significantly inhibited the release of 5-FU possibly due to an increase in the hydrophobic character of the coated tablet surface. This was possible by coating cohesive force strength reduction coating compositions (CCG-CH (70:30) and 0.3% magnesium silicate). Further, the FTIR-ATR and DSC analyses suggested the pivotal role of magnesium silicate in modifying the release of 5-FU from CCG-CH-coated tablets due to hydrogen bonding of its Si-O-Si or Mg-O groups with -OH moieties of CCG-CH.


Evidence for an hMSH3 defect in familial hamartomatous polyps.
Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and assayed for somatic mutation of PTEN, a gene inactivated in the germline of some hamartomatous polyposis syndrome patients. Ten hamartomatous polyposis syndrome patients were genotyped for germline mutations. Epithelial and nonepithelial polyp DNA were assayed for microsatellite instability (MSI) and PTEN frameshift mutation. DNA MMR and PTEN protein expression were assessed in all polyps by immunohistochemistry. In addition, 99 MSI-high sporadic CRCs and 50 each of hMLH1(-/-) and hMSH3(-/-) cell clones were examined for PTEN frameshifts. Twenty-five (58%) of 43 hamartomatous polyposis syndrome polyps demonstrated dinucleotide or greater MSI in polyp epithelium, consistent with hMSH3 deficiency. MSI domains lost hMSH3 expression, and PTEN expression was lost in polyps from germline PTEN patients; sporadic hamartomatous polyps did not show any of these findings. PTEN analysis revealed wild type exon 7 and 8 sequences suggestive of nonexistent or rare events for PTEN frameshifts; however, MSI-high sporadic CRC showed 11 (11%) of 99 frameshifts within PTEN, with 4 tumors having complete loss of PTEN expression. Subcloning hMLH1(-/-) and hMSH3(-/-) cells revealed somatic PTEN frameshifts in 4% and 12% of clones, respectively. Nondysplastic epithelium from hamartomatous polyposis syndrome polyps harbors hMSH3 defects, which may prime neoplastic transformation. Polyps from PTEN(+/-) patients lose PTEN expression, but loss is not a universal early feature of all hamartomatous polyposis syndrome. However, PTEN frameshifts can occur in hMSH3-deficient cells, suggesting that hMSH3 deficiency could drive hamartomatous polyposis syndrome tumorigenesis.


A profile of protein-protein interaction: Crystal structure of a lectin-lectin complex.
Proteins may utilize complex networks of interactions to create/proceed signaling pathways of highly adaptive responses such as programmed cell death. Direct binary interactions study of proteins may help propose models for protein-protein interaction. Towards this goal we applied a combination of thermodynamic kinetics and crystal structure analyses to elucidate the complexity and diversity in such interactions. By determining the heat change on the association of two galactose-specific legume lectins from Butea monosperma (BML) and Spatholobus parviflorus (SPL) belonging to Fabaceae family helped to compute the binding equilibrium. It was extended further by X-ray structural analysis of BML-SPL binary complex. In order to chart the proteins interacting mainly through their interfaces, identification of the nature of forces which stabilized the association of the lectin-lectin complex was examined. Comprehensive analysis of the BMLSPL complex by isothermal titration calorimetry and X-ray crystal structure threw new light on the lectin-lectin interactions suggesting of their use in diverse areas of glycobiology.


Development of an automated and High throughput UHPLC/MS based workflow for cleaning verification of potent compounds in the pharmaceutical manufacturing environment.
Cleaning verification (CV) is a critical step in the pharmaceutical manufacturing process to eliminate or reduce unacceptable contamination of a product as a result of insufficiently cleaned equipment surfaces. The main concern is cross contamination with active pharmaceutical ingredients (APIs) from previous runs that may impact patient safety. Current conventional approaches involve rather tedious sample preparation and analytical methods with relative lengthy analysis time. Potent APIs possessing low acceptable daily intake (ADI) values require analytical methods for CV with very low detection limits to confirm that these APIs are below their acceptance limits prior to the next manufacturing process. In this work, a novel end to end CV workflow was developed, which includes the automated sample and calibration solution preparation as well as high throughput analysis by ultra-high-performance liquid chromatography (UHPLC) coupled with single quadrupole mass spectrometry in multiple injection chromatography and selected ion monitoring mode (MIC-MS-SIM). The method was validated using ten model compounds. Acceptable specificity, linearity (R2 > 0.997) and single digit ng/mL LOQ and LOD were achieved for all model compounds. This approach was also successfully applied to the analysis of 22 internal CV samples from an internal program.


A Plasmodium falciparum aminopeptidase gene belonging to the M1 family of zinc-metallopeptidases is expressed in erythrocytic stages.
A new single copy gene has been isolated from Plasmodium falciparum, by immunoscreening a genomic DNA expression library. The gene appears devoid of introns, displays the classical A + T richness and codon usage of P. falciparum genes, and is transcribed into a 4 kb mRNA in erythrocytic stages. The deduced amino acid sequence corresponds to a 1056 residue protein (122 kDa) containing the canonical HExxHx18E signature of zinc-metallopeptidase active sites of the M1 family at position 467-490, a downstream conserved tyrosine residue involved in catalysis in position 551, and the GAMEN conserved motif characteristic of aminopeptidases in the M1 family, at position 431-435. The greatest similarities were found with aminopeptidases N of Escherichia coli and Haemophilius influenza (more than 80% identical residues in the canonical signature of the active site) but significant similarities centred on the active site region exist with all other members of the M1 family such as other prokaryotic aminopeptidases, eukaryotic aminopeptidases A and N and leukotriene A4 hydrolases (40-50% identical residues in the canonical signature of the active site). A polyclonal serum raised to a synthetic peptide deduced from the gene labelled schizont proteins of 96 and 68 kDa purified to homogeneity and both displaying aminopeptidase activity, as well as cytoplasmic structures in schizont stages.


Infrared intensities of methyl acetate, an interstellar compound - comparisons of three organic esters.
The mid-infrared (IR) spectra of the simplest aliphatic esters have been studied in the past in the solid, liquid, and gas phases with an emphasis on vibrational frequencies and peak assignments. However, relatively little has been published on the IR intensities of the amorphous forms of these compounds. These IR intensities are of particular interest to the astrochemical community as they are needed to help quantify laboratory measurements of the formation and destruction of extraterrestrial molecules, including esters. Here we report and compare IR intensities of three organic esters: methyl formate, methyl acetate, and methyl propionate, all studied with the same equipment and procedures. Of these three esters, our main interest is with methyl acetate, for which little quantitative IR work is available. For each ester, we report apparent absorption coefficients and band strengths, and compare them to earlier work. We also have calculated the first IR optical constants for both amorphous and crystalline methyl acetate. We use our new results to measure vapor pressures and a sublimation enthalpy for methyl acetate and to comment on a radiation-chemical experiment with methyl acetate and how it can be better quantified.


[Effects of bionic glue on experimental population dynamics of Paratrioza sinica and its natural enemies].
To find out whether and how the newly invented technique-bionic glue affects the main pest of wolf berry-Paratrioza sinica and its natural enemies Tamarixia lyciumi and Chrysopa septempunctata. Spraying bionic glue in field when wolf berry just geminated, investigated the adults and nymphs of P. sinica and it's natural enemies: adults of T. lyciumi and eggs of C. septempunctata. Bionic glue can significantly reduce the population number of P. sinica, but with little impacts on its natural enemies of T. lyciumi and C. septempunctata, and more experiments are need for further research.


Inverse gas chromatographic determination of solubility parameters of excipients.
The principle aim of this work was an application of inverse gas chromatography (IGC) for the estimation of solubility parameter for pharmaceutical excipients. The retention data of number of test solutes were used to calculate Flory-Huggins interaction parameter (chi1,2infinity) and than solubility parameter (delta2), corrected solubility parameter (deltaT) and its components (deltad, deltap, deltah) by using different procedures. The influence of different values of test solutes solubility parameter (delta1) over calculated values was estimated. The solubility parameter values obtained for all excipients from the slope, from Guillet and co-workers' procedure are higher than that obtained from components according Voelkel and Janas procedure. It was found that solubility parameter's value of the test solutes influences, but not significantly, values of solubility parameter of excipients.