Is Serum Angiotensin-Converting Enzyme Level Useful For Determining Necroinflammatory Activity In Chronic Hepatitis B Infection?
The purpose of this study was to investigate the relationship between the findings from liver biopsy and the serum angiotensin-converting enzyme (ACE) level to determine whether ACE might serve as a potential noninvasive sign of necroinflammatory activity in patients with Chronic Hepatitis B (CHB) infection. A total of 54 CHB patients referred for liver biopsy were enrolled in the study. Serum ACE levels were determined photometrically with a kinetic test. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), hepatitis B virus-deoxyribonucleic acid (HBV-DNA), histological activity index (HAI), and white blood cell counts were higher in patients with severe fibrosis, while albumin levels were low. The serum ACE levels showed a statistically significant correlation with HBV-DNA, HAI score, and ALT-AST levels. In this study, a statistically significant relation between serum ACE levels and HAI scores was observed. This represents the first analysis to compare necroinflammation of the liver and serum ACE levels. There may be some explanations that the suppression of hepatocyte growth factor (HGF) by Angiotensin II and increased inflammatory damage might be a reason for the correlation between HAI and ACE. Serum ACE levels, HBV-DNA levels, and serum transaminase levels might be used together as noninvasive markers for the prediction of necroinflammation in CHB patients.


Hepatitis C virus NS2 protein inhibits DNA damage pathway by sequestering p53 to the cytoplasm.
Chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality globally, and often leads to end-stage liver disease. The DNA damage checkpoint pathway induces cell cycle arrest for repairing DNA in response to DNA damage. HCV infection has been involved in this pathway. In this study, we assess the effects of HCV NS2 on DNA damage checkpoint pathway. We have observed that HCV NS2 induces ataxia-telangiectasia mutated checkpoint pathway by inducing Chk2, however, fails to activate the subsequent downstream pathway. Further study suggested that p53 is retained in the cytoplasm of HCV NS2 expressing cells, and p21 expression is not enhanced. We further observed that HCV NS2 expressing cells induce cyclin E expression and promote cell growth. Together these results suggested that HCV NS2 inhibits DNA damage response by altering the localization of p53, and may play a role in the pathogenesis of HCV infection.


A reason to hope.
The recent announcement that vaccination against HIV has been partially successful in Thailand gives scientists important clues for further developments.


Cardiopulmonary exercise test: A 20-year (2002-2021) bibliometric analysis.
The clinical application value of cardiopulmonary exercise test (CPET) has increasingly attracted attention, and related research has been increasing yearly. However, there is no summary analysis of the existing CPET literature. This is the first bibliometric analysis of publications in the CPET. CPET-related articles published between 2002 and 2021 were retrieved from the Web of Science Core Collection database. The search was limited to Articles and Reviews in English. CiteSpace software was used to conduct collaborative network analysis of countries/regions, institutions, authors, the co-occurrence of subject categories and keywords, and co-citation analysis of authors, journals, and references. A total of 4,426 publications were identified. During the study period, the number of published articles increased yearly. Developed countries from the Americas and Europe led the field. The University of Milan was the most prolific institution, with Ross Arena and Wasserman K being the most prolific and co-cited authors in the field, respectively. Cardiovascular System & Cardiology and Respiratory System were the main areas involved. Moreover, heart failure, oxygen uptake, and prognostic value were the central themes. CPET had attracted widespread attention, and the number of publications will increase substantially according to the current growth trends. In the future, CPET is expected to be further adopted in large-scale clinical studies as a means of assessing the functional ability of patients to verify the efficacy of related interventions. High-quality evidence-based medical CPET-related indicators is expected to be used in clinical diseases risk prediction.


Facile and Green Preparation of Pectin/Cellulose Composite Films with Enhanced Antibacterial and Antioxidant Behaviors.
Novel bioactive films based on pectin and cellulose (PC) with different loadings of tea polyphenols and cinnamaldehyde were successfully prepared. A thermal stability was tested, and the results showed that the thermal stability decreased slightly after loading with cinnamaldehyde and tea polyphenols, compared to PC films. The antimicrobial and antioxidant capacities were also investigated. Results showed that PC composite films had good DPPH radical and hydroxyl radical scavenging activities and excellent antibacterial activities against Escherichia coli, Candida albicans and Staphylococcus aureus. Based on the results, the great antioxidant and antibacterial activities of the tea polyphenol and cinnamaldehyde loaded PC films make them suitable for food packaging and preservation.


Why are behaviors of children suffering from various neuronopathic types of mucopolysaccharidoses different?
Mucopolysaccharidoses (MPS) are inherited metabolic disorders from the group of lysosomal storage diseases (LSD). They arise from mutations causing dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs) in lysosomes. Impaired degradation of these compounds results in their accumulation in cells and dysfunction of most tissues and organs of patients. If heparan sulfate (HS) is the sole or one of stored GAGs, brain functions are also affected. However, despite the fact that products of incomplete degradation of the same chemical, HS, are accumulated in brains of patients suffering from Hurler disease (MPS type I), Hunter disease (MPS type II), Sanfilippo disease (MPS type III) and Sly disease (MPS type VII), and obvious deterioration of brain functions occur in these patients, their behavior is considerably different between various types of MPS. Here we asked the question about biochemical reasons of these differences. We performed theoretical analysis of products of incomplete HS degradation that accumulate in tissues of patients diagnosed for these diseases. A correlation between chemical structures of incompletely degraded HS and behaviors of patients suffering from particular MPS types was found. We propose a hypothesis that particular chemical moieties occurring at the ends of incompletely degraded HS molecules may determine characteristic behavioral disturbances, perhaps due to chemical reactions interfering with functions of neurons in the brain. A possible experimental testing of this hypothesis is also proposed. If the hypothesis is true, it might shed some new light on biochemical mechanisms of behavioral problems occurring not only in MPS but also in some other diseases.


Late evolution of giant verruciform xanthoma in the setting of CHILD syndrome.
Congenital hemidysplasia with ichthyosiform erythroderma and limb defects (CHILD) syndrome is a rare X-linked dominant disorder that is characterized by peculiar cutaneous features commonly associated with skeletal and internal organ involvement. Cutaneous verruciform xanthoma is an uncommon cutaneous manifestation of congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome. We present a case presenting with a late onset of a large verruciform xanthoma of the right foot, in addition to the more typical cutaneous features of congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome.


Impact of climate variation on mosquito abundance in California.
Temporal variation in the abundance of the encephalitis virus vector mosquito, Culex tarsalis Coquillet, was linked significantly with coincident and antecedent measures of regional climate, including temperature, precipitation, snow pack, and the El Niño/Southern Oscillation anomaly. Although variable among traps, historical records that spanned two to five decades revealed climate influences on spring and summer mosquito abundance as early as the previous fall through early summer. Correlations between winter and spring precipitation and snow pack and spring Cx. tarsalis abundance were stronger than correlations with summer abundance. Spring abundance was also correlated positively with winter and spring temperature, whereas summer abundance correlated negatively with spring temperature and not significantly with summer temperature. Correlations with antecedent climate provide the opportunity to forecast vector abundance and therefore encephalitis virus risk, a capability useful in intervention decision support systems at local and state levels.


Cerebral perfusion deficits in divers with neurological decompression illness.
Cerebral perfusion deficits detected by injection of 99Tcm-hexamethylpropyleneamine oxime (HMPAO) and single photon emission tomography is said to correlate well with clinical findings in divers with neurological decompression illness. We studied 12 divers. Six had residual cerebral signs (group 1) and six had no residual cerebral symptoms or signs (group 2). Perfusion deficits were as common in group 2 as in group 1. The site of the deficit did not correlate well with either the neurological findings at presentation or the residual clinical signs after treatment. The data suggest that claims that HMPAO scanning correlates with clinical findings and can be used for patients management were incorrect.


Human gamma/delta T cells responding to mycobacteria.
Responses of human T cells against mycobacteria and mycobacterial components were analysed. T cells expressing either the alpha/beta or the gamma/delta T cell receptor were selected from human peripheral blood lymphocytes and proliferative responses to intact mycobacteria and to molecular mass-fractionated mycobacterial lysates were determined. alpha/beta T cells responded primarily to fractions greater than 30 kDa. Protease digestion abolished the stimulating activities for alpha/beta T cells, confirming that alpha/beta T cells respond to protein components. In contrast components recognized by gamma/delta T cells proved resistant to protease digestion. In limiting dilution studies, frequencies of proliferating gamma/delta T cells remained virtually unaltered by protease treatment of stimulating lysates, while those of alpha/beta T cells became almost undetectable. Furthermore, only few gamma/delta T cells responded to the 65 kDa heat shock protein. Our data indicate that, unlike alpha/beta T cells, gamma/delta T cells respond to mycobacterial components which are resistant to vigorous protease digestion.


Decreased levels of Cx43 gap junctions result in ameloblast dysregulation and enamel hypoplasia in Gja1Jrt/+ mice.
Coordinated differentiation of the ameloblast cell layer is essential to enamel matrix protein deposition and subsequent mineralization. It has been hypothesized that this process is governed by Cx43-based gap junctional intercellular communication as oculodentodigital dysplasia (ODDD) patients harboring autosomal-dominant mutations in Cx43 exhibit enamel defects typically resulting in early adulthood tooth loss. To assess the role of Cx43 in tooth development we employ a mouse model of ODDD that harbors a G60S Cx43 mutant, Gja1(Jrt)/+, and appears to exhibit tooth abnormalities that mimic the human disease. We found that total Cx43 plaques at all stages of ameloblast differentiation, as well as within the supporting cell layers, were greatly reduced in Gja1(Jrt)/+ incisors compared to wild-type littermate controls. To characterize the Gja1(Jrt)/+ mouse tooth phenotype, mice were sacrificed prior to tooth eruption (postnatal day 7), weaning (postnatal day 21), and adulthood (2 months postnatal). A severely disorganized Gja1(Jrt)/+ mouse ameloblast layer and abnormal accumulation of amelogenin were observed at stages when the cells were active in secretion and mineralization. Differences in enamel thickness became more apparent after tooth eruption and incisor exposure to the oral cavity suggesting that enamel integrity is compromised, leading to rapid erosion. Additional analysis of incisors from mutant mice revealed that they were longer with a thicker dentin layer than their wild-type littermates, which may reflect a mechanical stress response to the depleted enamel layer. Together, these data show that reduced levels of Cx43 gap junctions result in ameloblast dysregulation, enamel hypoplasia, and secondary tissue responses.


Characterization of growth-restricted fetuses with breakdown of the brain-sparing effect diagnosed by spectral Doppler.
To characterize serial findings of the middle cerebral artery (MCA) and umbilical artery (UA) flow patterns, their relationship to each other, and neonatal outcomes in growth-restricted fetuses. Serial pulsatility indices (PIs) from MCA and UA Doppler waveforms were measured in 41 growth-restricted fetuses until Cesarean delivery. We found three patterns, as follows: phase 1 (n = 27), UA PI < MCA PI (no brain-sparing effect); phase 2 (n = 11), UA PI > MCA PI (brain-sparing effect); phase 3 (n = 3), both PIs elevated with the absence of end-diastolic flow or presence of reverse end-diastolic flow, which was designated as the 'breakdown of the brain-sparing effect'. Umbilical cord blood gas data at delivery were compared between each group. Age at delivery and body weights were significantly different for each phase. The mean body weights in all phases were significantly diminished from Japanese standard body weights, indicating growth restriction. The phase 3 pH and base excess were significantly different from those of the other two phases. Growth-restricted fetuses which suffered from the state of breakdown of the brain-sparing effect were delivered early with severe growth restriction and mild metabolic acidosis. The change from decreased to increased MCA PI along with increasing UA PI may predict a severely growth-restricted infant.


[Biofeedback and relaxation for patients with hypertension].
We have known for decades that essential hypertension significantly contributes to many physical diseases. In most cases, hypertension results from a person's perception of stress producing events or situations. According to Greenberg, when a person is confronted by a situation or an event, the person must perceive it as either positively or negatively stressful. If it is perceived as positively stressful, a series of psychological reactions are incurred followed by physiological reactions. If these psychophysiological manifestations persist, the person is then faced with possible pathological conditions. This study attempted to support the hypothesis that people with hypertension should be able to benefit from biofeedback and relaxation techniques. Using these techniques, they will be better able to recognize and understand perceived stressful events or situations and will therefore act appropriately. The purpose of this study is to examine the effects of biofeedback, relaxation and the combination of both techniques on medically diagnosed hypertensive patients. More specifically, the study examined the following questions: What is the clients' ability to lower their blood pressure using biofeedback, relaxation and the combination of both techniques? To what capacity can clients reduce their biofeedback and relaxation training programme? Twenty-three males, aged 40 to 70 years (M = 54 years), who were registered with a cardiovascular disease prevention and rehabilitation centre, volunteered to participate in this study. For five weeks, clients trained Tuesdays and Thursdays, one hour per session. Compliance to the training programme was respected by using only those clients who had missed fewer than three of the sessions. The results showed little statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)


Gastric mammalian target of rapamycin signaling regulates ghrelin production and food intake.
Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. Mammalian target of rapamycin (mTOR) is an intracellular fuel sensor critical for cellular energy homeostasis. Here we showed the reciprocal relationship of gastric mTOR signaling and ghrelin during changes in energy status. mTOR activity was down-regulated, whereas gastric preproghrelin and circulating ghrelin were increased by fasting. In db/db mice, gastric mTOR signaling was enhanced, whereas gastric preproghrelin and circulating ghrelin were decreased. Inhibition of the gastric mTOR signaling by rapamycin stimulated the expression of gastric preproghrelin and ghrelin mRNA and increased plasma ghrelin in both wild-type and db/db mice. Activation of the gastric mTOR signaling by l-leucine decreased the expression of gastric preproghrelin and the level of plasma ghrelin. Overexpression of mTOR attenuated ghrelin promoter activity, whereas inhibition of mTOR activity by overexpression of TSC1 or TSC2 increased its activity. Ghrelin receptor antagonist d-Lys-3-GH-releasing peptide-6 abolished the rapamycin-induced increment in food intake despite that plasma ghrelin remained elevated. mTOR is therefore a gastric fuel sensor whose activity is linked to the regulation of energy intake through ghrelin.


[The prefiguration of a museum of the Hand of Man].
The author has created a foundation, acknowledged as being of public benefit, whose purpose is to set up a "Museum of the Hand of Man", conceived as a coordination and research center on the hand. An attempt at systematizing a prefiguration of this institution is proposed, with five subsectors: the original of this institution is proposed, with five subsectors: the original hand, the experienced hand, the hand and culture, the hand and society, and the hand as a symbol. In addition, a collection of publications on these various aspects of the hand is projected.


The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis.
Hyperprolactinaemia is commonly induced by antipsychotic medications that have dopamine-blockade as their main mechanism of action. The purpose of this study was to assess the effect of antipsychotic-induced hyperprolactinaemia on hypothalamic-pituitary-gonadal axis (HPG) function.HPG axis function was assessed in 67 consecutive outpatients who were diagnosed with schizophrenia and stabilized for a period of not less than 2 years on typical antipsychotic medication, by means of clinical history, relevant questionnaires and measurement of plasma prolactin, estradiol, progesterone, testosterone, LH, FSH, sex hormone binding globulin, and TSH levels. Normative laboratory data were used to assess whether hormone levels fell within the reference range for a normal population. There was a significant correlation between dose of medication and plasma prolactin levels for the total group (P<0.001). Prolactin levels were significantly negatively associated with sex hormone levels in females (P<0.05). Males taking antipsychotic medication had a mean prolactin level of 404.1m/IU and mean gonadotrophin and sex hormone levels that fell within normal limits. The results of this study indicate that neuroleptic-induced prolactin secretion is a dose-related side effect and, in females, the level of hyperprolactinaemia is correlated with the degree of suppression of the HPG axis. Women taking long-term prolactin-raising antipsychotic medications are likely to be hyperprolactinaemic and have an associated hypogonadal state. In males, prolactin levels remain within normal limits, but at the upper end, with no apparent disturbance of reproductive hormones.


ACSL3 is a novel GABARAPL2 interactor that links ufmylation and lipid droplet biogenesis.
While studies of the autophagy-related (ATG) genes in knockout models have led to an explosion of knowledge about the functions of autophagy components, the exact roles of LC3 and GABARAP family proteins (human ATG8 equivalents) are still poorly understood. A major drawback in understanding their roles is that the available interactome data has largely been acquired using overexpression systems. To overcome these limitations, we employed CRISPR/Cas9-based genome-editing to generate a panel of cells in which human ATG8 genes were tagged at their natural chromosomal locations with an N-terminal affinity epitope. This cellular resource was employed to map endogenous GABARAPL2 protein complexes using interaction proteomics. This approach identified the ER-associated protein and lipid droplet (LD) biogenesis factor ACSL3 as a stabilizing GABARAPL2-binding partner. GABARAPL2 bound ACSL3 in a manner dependent on its LC3-interacting regions, whose binding site in GABARAPL2 was required to recruit the latter to the ER. Through this interaction, the UFM1-activating enzyme UBA5 became anchored at the ER. Furthermore, ACSL3 depletion and LD induction affected the abundance of several ufmylation components and ER-phagy. Together these data allow us to define ACSL3 as a novel regulator of the enigmatic UFM1 conjugation pathway.


Anthropometric failures and its associated factors among preschool-aged children in a rural community in southwest Ethiopia.
In 2019, 144 million under-five-year-old children were stunted, and 47 million were wasted globally. In Ethiopia, approximately 350,000 children are estimated to die each year. Preschool aged children need focused attention because this age group not only has special needs, but also forms the platform for growth and development of all children. Under nutrition among preschool children is the result of a complex interplay of diverse elements, such as birth weight, household access to food, availability and use of drinking water. This study aimed at determining the anthropometric failures and associated factors using composite indictors. A community-based cross-sectional study design was used among randomly selected 588 caregivers with pre-school aged children. Under-nutrition of pre-school aged children was computed by using the composite index of anthropometric failure. A multi-stage sampling technique followed by a systematic random sampling technique was used to select study participants. Structured questionnaires were used to collect data. WHO Anthro software was used to calculate height for age, weight for age and weight for height. The overall prevalence of anthropometric failure (CIAF). Both bivariable and multivariable binary logistic regressions were used to identify factors associated with under-nutrition. The overall prevalence of under-nutrition among pre-school children was 50.8%, which was significantly associated with being a female (AOR = 1.51, CI: 1.076, 2.12), being from a large family (AOR = 1.78, CI: 1.19, 2.663), having acute respiratory infection (AOR = 1.767, CI: 1.216, 2.566), lack of improved source of drinking water (AOR = 1.484 CI: 1.056, 2.085) and poor dietary diversity score (AOR = 1.5, CI: 1.066, 2.112). The study area has a high prevalence of CIAF in pre-school aged children. The CIAF was found to be significantly associated with the sex of the child, family size, ARI within the last two weeks, and dietary diversity score. To promote the use of family planning and the prevention of infectious diseases, health education is required. The government should adapt CIAF as a metric for assessing children's nutritional status.


In Vitro Toxicity of Bone Graft Materials to Human Mineralizing Cells.
Bone graft materials from synthetic, bovine, and human sources were analyzed and tested for in vitro cytotoxicity on dental pulp stem cells (DPSCs) and osteosarcoma cells (Saos-2). Raman spectroscopy indicated significant amounts of collagen only in human bone-derived materials, where the mineral to protein ratio was 3.55 ± 0.45, consistent with bone. X-ray fluorescence revealed tungsten (W) concentrations of 463 ± 73, 400 ± 77, and 92 ± 42 ppm in synthetic, bovine, and human bone chips, respectively. When these chips were added to DPSCs on tissue culture plastic, the doubling times after two days were the same as the controls, 16.5 ± 0.5 h. Those cultured with synthetic or bovine chips were 96.5 ± 8.1 and 25.2 ± 1.4 h, respectively. Saos-2 was more sensitive. During the first two days with allogeneic or bovine graft materials, cell numbers declined. When DPSC were cultured on collagen, allogeneic and bovine bone chips did not increase doubling times. We propose cytotoxicity was associated with tungsten, where only the concentration in human bone chips was below 184 ppm, the value reported as cytotoxic in vitro. Cells on collagen were resistant to bone chips, possibly due to tungsten adsorption by collagen.


Amylin and selective glucoregulatory peptide alterations during prolonged exercise.
Amylin is a pancreatic β-cell peptide that facilitates the regulation of blood glucose concentration by inhibiting release of glucagon and modulating gastric emptying. Prolonged exercise may alter amylin and aid in the maintenance of blood glucose concentration; however, no studies have investigated the effects of prolonged exercise on amylin. This study aimed to determine the effects of 90 min of treadmill exercise on amylin and other glucoregulatory hormone responses in a postprandial state. Eight young healthy males completed a preliminary trial for VO2max and body composition determination and subsequent experimental and control trials in a counterbalanced manner. The experimental trial subjects arrived at the laboratory at 8:00 a.m., 1 h after consumption of a standard nutrient beverage (Ensure Plus®). At 9:50 a.m., subjects initiated 90 min of treadmill exercise at 60% of VO2max. Blood samples were collected twice before exercise, every 18 min during exercise, and every 20 min during 1 h of recovery. A resting control trial was conducted in an identical manner without VO2 assessment. Plasma glucose and leptin concentrations remained stable across exercise, whereas lactate significantly increased to peak at 18 min of exercise then gradually declined. Amylin, insulin, and C-peptide values significantly declined over the trials, with no difference between exercise and control days. Glucagon area-under-the-curve concentrations were significantly greater during the exercise than the control trials. There was a significant time effect and trial effect for cortisol with a higher concentration during the experimental trial than during the control trial. In a postprandial state, prolonged exercise stimulates glucagon and cortisol increases that are associated with stable blood glucose and leptin concentrations; however, similar to postprandial state control condition, insulin, C-peptide, and amylin concentrations decline.


A mutation in the vesicle-trafficking protein VAPB causes late-onset spinal muscular atrophy and amyotrophic lateral sclerosis.
Motor neuron diseases (MNDs) are a group of neurodegenerative disorders with involvement of upper and/or lower motor neurons, such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), progressive bulbar palsy, and primary lateral sclerosis. Recently, we have mapped a new locus for an atypical form of ALS/MND (atypical amyotrophic lateral sclerosis [ALS8]) at 20q13.3 in a large white Brazilian family. Here, we report the finding of a novel missense mutation in the vesicle-associated membrane protein/synaptobrevin-associated membrane protein B (VAPB) gene in patients from this family. Subsequently, the same mutation was identified in patients from six additional kindreds but with different clinical courses, such as ALS8, late-onset SMA, and typical severe ALS with rapid progression. Although it was not possible to link all these families, haplotype analysis suggests a founder effect. Members of the vesicle-associated proteins are intracellular membrane proteins that can associate with microtubules and that have been shown to have a function in membrane transport. These data suggest that clinically variable MNDs may be caused by a dysfunction in intracellular membrane trafficking.


Prehypertension: a meta-analysis of the epidemiology, risk factors, and predictors of progression.
We investigated the prevalence and risk factors of prehypertension, as well as the predictors of progression from prehypertension to hypertension. To do this, we performed a systematic review and meta-analysis of cross-sectional and longitudinal studies, after unrestricted searches of PubMed and The Cochrane Library through September 2010. In addition, we reviewed references, major textbooks, and review articles. Pooled prevalence, standardized mean differences, and odds ratios were estimated by using a random-effects model. Twenty-six articles met our inclusion criteria; these included 20 cross-sectional and 6 longitudinal studies, with a total sample of 250,741 individuals. The overall pooled prevalence of prehypertension was 36%. The pooled prevalence among males was higher than that among females (40% vs 33%). The pooled standardized mean difference for body mass index was 1.37 (95% confidence interval [CI], 1.20-1.55); for total cholesterol, 8.08 (95% CI, 6.71-9.46); for low-density-lipoprotein cholesterol, 5.14 (95% CI, 3.09-7.18); and for fasting plasma glucose, 4.23 (95% CI, 3.28-5.18); all of which showed more significant results in females. The pooled odds ratio was 1.13 (95% CI, 0.93-1.37) for smoking and 0.98 (95% CI, 0.69-1.39) for drinking. In addition, factors such as older age at baseline, male sex, Mongolian race, and being overweight or obese were predictors of progression to hypertension, according to descriptive analysis. The prevalence of prehypertension was relatively high, especially for males. There were many modifiable risk factors associated with prehypertension, to which healthcare providers should pay more attention.


Few SARS-CoV-2 infections detected in Newfoundland and Labrador in the absence of Public Health Laboratory-based confirmation.
To assess the incidence of COVID-19 infection in the absence of a confirmatory test in persons suspecting they contracted COVID-19 and elucidate reasons for their belief. We recruited persons with a confirmed COVID-19 diagnosis and persons who believed they may have contracted COVID-19 between December, 2019 and April, 2021 into a study of immunity against SARS-CoV-2. An intake questionnaire captured their perceived risk factors for exposure and symptoms experienced, including symptom duration and severity. ELISA testing against multiple SARS-CoV-2 antigens was done to detect antibodies against SARS-CoV-2. No participant had received COVID-19 vaccination prior to the time of testing. The vast majority of study subjects without Public Health confirmation of infection had no detectable antibodies against SARS-CoV-2. Suspected infection with SARS-CoV-2 generally involved experiencing symptoms common to many other respiratory infections. Unusually severe or persistent symptoms often supported suspicion of infection with SARS-CoV-2 as did travel or contact with travelers from outside Newfoundland and Labrador. Rare cases in which antibodies against SARS-CoV-2 were detected despite negative results of Public Health testing for SARS-CoV-2 RNA involved persons in close contact with confirmed cases. Broad public awareness and declaration of pandemic status in March, 2020 contributed to the perceived risk of contracting COVID-19 in Newfoundland and Labrador from late 2019 to April 2021 and raised expectation of its severity. Serological testing is useful to diagnose past infection with SARS-CoV-2 to accurately estimate population exposure rates.


Reference intervals for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in infants' day 14-30 of life and a comparison with other studies.
Objectives Established reference intervals of thyroid function in neonates are important; however, studies often consist of a small sample size or lack of clinical information. We aim to define reference intervals for thyroid-stimulating hormone (TSH) and free thyroxine (FT4) for infants aged 14-30 days. We also reviewed follow-up TSH for infants with initial values 10-20 mIU/L. Methods Venous TSH and FT4 of term babies aged 14-30 days with breast milk jaundice that had thyroid function test performed as part of a prolonged jaundice workout from September 2016 to March 2017 were analyzed. Electronic medical records were reviewed to ensure only well babies with no pathological causes of jaundice or conditions that may affect thyroid function were included. TSH and FT4 were analyzed using immunoassay analyzer Dxl 800, Beckman Coulter. Results There were no correlations between FT4 and TSH with gender, birth weight and ethnicity. Correlation coefficient between FT4 and total bilirubin was weak at 0.138 (p=0.001). No association was found between TSH and bilirubin levels. Mean FT4 was higher in the younger age group day 14-21 (p<0.01). There was no significant difference in TSH values between the age groups. Infants with mildly elevated TSH 10-20 mIU/L had normalized values on follow-up (mean, 11.41 vs. 4.42 mIU/L; p<0.01; 95%CI, 5.88-8.09). The following reference intervals (2.5-97.5th percentile) were derived: FT4 day 14-21 (n=513): 11.59-21.00 pmoL/L; FT4 day 22-30 (n=66): 10.14-19.60 pmoL/L; TSH day 14-30 (n=579): 1.90-10.34 mIU/L. Comparison between studies showed variations of reference intervals with different manufacturer assays, age and methodology. Conclusions Our reference intervals would be useful in the clinical setting. Infants with mildly elevated TSH could be monitored first instead of immediate treatment.


Aerobic Anoxygenic Phototrophic Bacteria Promote the Development of Biological Soil Crusts.
Chlorophyll-containing oxygenic photoautotrophs have been well known to play a fundamental role in the development of biological soil crusts (BSCs) by harvesting solar radiations and providing fixed carbon to the BSCs ecosystems. Although the same functions can be theoretically fulfilled by the widespread bacteriochlorophyll-harboring aerobic anoxygenic phototrophic bacteria (AAnPB), whether AAnPB play a role in the formation of BSCs and how important they are to this process remain largely unknown. To address these questions, we set up a microcosm system with surface sands of the Hopq desert in northern China and observed the significant effects of near-infrared illumination on the development of BSCs. Compared to near-infrared or red light alone, the combined use of near-infrared and red lights for illumination greatly increased the thickness of BSCs, their organic matter contents and the microalgae abundance by 24.0, 103.7, and 1447.6%, respectively. These changes were attributed to the increasing abundance of AAnPB that can absorb near-infrared radiations. Our data suggest that AAnPB is a long-overlooked driver in promoting the development of BSCs in drylands.


Pharmacotherapy of regional melanoma therapy.
In-transit melanoma metastases develop within regional dermal and subdermal lymphatics before reaching the regional lymph nodes. The prognosis is poor and comparable to multiple nodal metastases. Isolated limb infusion (ILI) or perfusion (ILP) are effective treatments for unresectable, in-transit melanoma, with response rates reaching 95%. Although ILI and ILP are more effective than systemic therapy, most patients will recur, thus highlighting the need for newer strategies to improve durable response rates. We review historical and current literature from 1958 to 2009 regarding regional therapy for melanoma, with focus on the ILI and ILP techniques, pharmacokinetics and resistance mechanisms of melphalan. Alternative therapies, adjunct strategies and new targeted therapies aimed at improving response rates and long-term remission are also discussed. The reader will gain a comprehensive review on regional pharmacotherapy for melanoma, including alternative therapies, adjunct strategies and new targeted therapies. Regional chemotherapy is a viable, evolving treatment for patients with in-transit melanoma and a springboard for ongoing research aimed at improving therapies for malignant melanoma.


TGF-β1 up-regulates the expression of PDGF-β receptor mRNA and induces a delayed PI3K-, AKT-, and p70(S6K) -dependent proliferative response in activated hepatic stellate cells.
Transforming growth factor beta 1 (TGF-β1) is a pleiotropic cytokine that activates hepatic stellate cell (HSC) proliferation, but inhibits parenchymal cell proliferation. Therefore, we hypothesize that TGF-β1 regulates HSC proliferation and elucidated its molecular action. In order to elucidate the molecular mechanism whereby TGF-β1 up-regulates platelet derived growth factor beta (PDGF-β) receptor mRNA and induces a delayed proliferation of HSC, we used proliferation and apoptosis assays as well as RT-PCR, Western blot analysis, immunostaining, and flow cytometry in mouse and rat HSC. We show that TGF-β1 markedly induces the proliferation of mouse HSC in culture with concomitant 2.1-fold (p < 0.001) stimulation in [(3) H]-thymidine incorporation into cellular DNA. This induction is maximal between 24 and 36 hours postcytokine exposure that is triggered by 7.6-fold (p < 0.001) up-regulation of PDGF-β receptor mRNA and associated increase in PDGF-β receptor protein after 48 hours. TGF-β1-dependent HSC proliferation is mimicked by H2 O2 that is inhibited by catalase, implying that TGF-β1 action is mediated via reactive oxygen species. HSC proliferation is blunted by PDGF-β receptor-neutralizing antibody as well as by specific inhibitors of PI3 kinase (PI3K), AKT, and p70(S6K) , indicating that the action of TGF-β1 involves the activation of PDGF-β receptor via the PI3K/AKT/p70(S6K) signaling pathway. TGF-β1 also induces a reorganization of actin and myosin filaments and cell morphology leading to the formation of palisades although their myosin and actin contents remained constant. These findings suggest that TGF-β1-mediated oxidative stress causes the transdifferentiation of HSC and primes them for extracellular matrix (ECM) deposition and scar contraction. We conclude that liver injury up-regulates TGF-β1 that inhibits parenchymal cell proliferation, but stimulates HSC proliferation leading to the production of ECM and type I collagen resulting in fibrosis.


Optimized QuEChERS Method Combined with UHPLC-MS/MS for the Simultaneous Determination of 15 Mycotoxins in Liquorice.
In our study, a reliable and rapid analytical method for the simultaneous determination of 15 mycotoxins (aflatoxin B1, aflatoxin B2, aflatoxin G1, aflatoxin G2, alternariol, agroclavine, citrinin, diacetoxyscirpenol, deoxynivalenol, fumonisin B1, fumonisin B2, ochratoxin A, sterigmatocystin, T-2 toxin, and zearalenone) in liquorice using ultra-HPLC coupled to tandem MS was developed and validated. Due to the complex ingredients in liquorice, we chose a QuEChERS-based extraction procedure as the sample pretreatment. Meanwhile, for the first time, acetate buffer was used to replaced water, which can greatly reduce the concentration of formic acid in acetonitrile, which further reduces the extraction efficiency of impurities. The optimal combination of adsorbents is 150 mg primary secondary amine, 150 mg silica gel, 600 mg octadecylsilane, and 900 mg anhydrous magnesium sulfate. Electrospray ionization in both positive- and negative-ionization modes was applied to detect all the mycotoxins in a single run time of 15 min, with LOQs in the range of 0.125-2.5 μg/kg. The recoveries of determination obtained were in the range of 81.0-104.7%, whereas the analytes could be accurately quantified in the 0.25-625 μg/kg concentration range, with all coefficients being >0.992. Intra- and interday reproducibility were lower than 5.5 and 8.9%, respectively, for all analytical mycotoxins. The validated method was finally applied to screen mycotoxins in 31 batches of real samples collected from drugstores and hospitals in Shanghai, China. Our survey findings show that six mycotoxins were detected, including alternariol, citrinin, deoxynivalenol, fumonisin B1, ochratoxin, and zearalenone, and that the positive rate of mycotoxins was 54.8% in real samples, ranging from 3.37 to 520.6 μg/kg.


Complex dynamics and synchronization of delayed-feedback nonlinear oscillators.
We describe a flexible and modular delayed-feedback nonlinear oscillator that is capable of generating a wide range of dynamical behaviours, from periodic oscillations to high-dimensional chaos. The oscillator uses electro-optic modulation and fibre-optic transmission, with feedback and filtering implemented through real-time digital signal processing. We consider two such oscillators that are coupled to one another, and we identify the conditions under which they will synchronize. By examining the rates of divergence or convergence between two coupled oscillators, we quantify the maximum Lyapunov exponents or transverse Lyapunov exponents of the system, and we present an experimental method to determine these rates that does not require a mathematical model of the system. Finally, we demonstrate a new adaptive control method that keeps two oscillators synchronized, even when the coupling between them is changing unpredictably.


Partner-Level and Sexual Networking Factors Are Associated With Vaccine-Type and Nonvaccine-Type Human Papillomavirus Infection After Vaccine Introduction in Young Women.
The aim of this study was to determine individual-level, partner-level, and sexual networking factors associated with vaccine- and non-vaccine-type human papillomavirus (HPV) in young women, by vaccination status. Sexually experienced women 13 to 26 years old (n = 784) completed a survey and were tested for 36 HPV genotypes. We determined factors associated with 4-valent vaccine-type HPV (HPV-6, HPV-11, HPV-16, HPV-18) and non-vaccine-type HPV among vaccinated and unvaccinated women, using univariable and multivariable logistic regression models. Participants' mean age was 19.2 years, 77.7% had received ≥1 vaccine dose, and 7.7% were positive for vaccine-type HPV (HPV-6, HPV-11, HPV-16, and/or HPV-18). Factors associated with vaccine-type HPV in vaccinated women included gonorrhea history (adjusted odds ratio [AOR], 2.71), new female sex partner(s) (AOR, 4.79), age at vaccination (≥15 vs. <15 years; AOR, 2.47), and age discordance with most recent partner (don't know vs. discordant; AOR, 9.17). Factors associated with non-vaccine-type HPV in vaccinated women included history of sexually transmitted infection (AOR, 2.69), male most recent partner (AOR, 2.85), age of first sex (AOR, 1.15), and partner concurrency (don't know vs. 1 other partner; AOR, 2.03). Factors associated with vaccine-type HPV in unvaccinated women included new female sex partner(s) (AOR, 7.45) and partner concurrency (don't know vs. no; AOR, 2.95). Factors associated with non-vaccine-type HPV in unvaccinated women included race (White vs. multiracial; AOR, 4.10) and partner concurrency (don't know vs. 0; AOR, 4.65). Novel findings of this study, including associations between female sex partners and HPV, and between not knowing about partner concurrency and HPV, have implications for sexual education, clinical counseling, and public health interventions.


Functional Deimmunization of Interferon Beta-1b by Identifying and Silencing Human T Cells Epitopes.
Interferonbeta-1b (IFNβ-1b) developed as therapeutic protein for the treatment of multiple sclerosis (MS). Studies have been shown that Long-term usage of this protein can lead to the development of anti-drug antibodies (ADAs) and this phenomenon cause total loss or reduced efficacy of IFNβ-1b. The aim of this study was to predict and silence IFNβ-1b T-cells epitopes by in silico methods and genetic engineering. Based on bioinformatics studies we identified optimal sets of conservative point mutations for eliminating T-cells epitopes in IFNβ-1b protein. Four synthetic genes with desirable mutation constructed and PET26b+ was used as an expression vector in E. coli. The expression of this proteins confirmed by SDS-PAGE and Western blotting, consequently, IFNβ-1b proteins was purified by His-tag chromatography. To determined activity of mutants' variants anti-proliferative and anti-viral activity compared to wild form was evaluated using MTT assay in A549 and Vero cells lines respectively. Also the immunogenicity of mutant proteins compared with Betaseron measured in BALB/c mice. The in vitro bioactivity analysis demonstrated that functional activities of all mutant proteins were maintained and is the same as biological activity of Betaseron. Pharmacokinetic studies suggest that, in engineered proteins that contain substitution of Histidine to Glutamic Acid at position 131 (mut 2 and mut 1+2) antibodies response reduced by about 50%, as compared to that for Betaseron. Computational analysis expedites identification and prediction of epitopes in therapeutic protein, therefore, we used immunoinformatic tools for modification of dominant T-cell epitope in IFNβ-1b protein, and this strategy has capacity to create proteins which have naturally reduced immunogenicity.


The Ki-67 index and survival in non-small cell lung cancer: a review and relevance to positron emission tomography.
We reviewed the current literature to discover the range of studies covering tissue-based and noninvasive methods for determining tumor stage and the prognostic value of staging in non-small cell lung cancer. Despite refinements in staging of non-small cell lung cancer, each stage remains heterogeneous because each stage contains patients who are at higher risk for recurrence than other patients within the same stage. Tissue-based and noninvasive methods have been investigated to complement tumor stage in assessing non-small cell lung cancer prognosis. The prognostic significance of tumor proliferation assessed by Ki-67 protein expression has been demonstrated in non-small cell lung cancer. Recent positron emission tomography studies have also shown both prognostic value in non-small cell lung cancer uptake of [F-18] fluorodeoxyglucose (FDG) and correlation between non-small cell lung cancer FDG uptake and tumor proliferation. We reviewed the prognostic significance of Ki-67 expression in non-small cell lung cancer and related it to positron emission tomography.


[Evaluation of the vascular endothelial growth factor in children and adolescents with type 1 diabetes].
Diabetes type 1 is the chronic disease, leading to many acute and late complications. Pathogenesis of the late complications is not fully understood. Lately, growth factors, and especially vascular endothelial growth factor (VEGF) are gaining great interest as potential risk factors of late diabetic complications, mainly nephropathy and retinopathy The aim of the study was evaluation of the level of VEGF in children and adolescents with diabetes type 1, and searching for correlation between level of this cytokine and microangiopathy and metabolic control. 68 young diabetic type patients were studied, aged 8-20 yrs (x = 15.54 yrs), suffering from diabetes type 1 from 2.3-16.5 yrs (x = 7.84 yrs), 34 boys, 34 girls. They were all under control of Outpatient Diabetic Department. Control group were healthy children, age and gender matched. Metabolic control was assessed on the basis of HbA1c level. All children underwent ophthalmology examination, microalbuminuria was evaluated in 24 hours urine samples. VEGF was estimated with use of immunoenzymatic method (RD Systems). In the study group we found: significantly higher levels of VEGF compared to control group (328.68 +/- 251.6 vs 132.19 +/- 85.51 pg/ml: p<0.05). We did not find any differences between genders in VEGF level. VEGF increases with diabetes duration time, and the highest values are in children with diabetes duration over 10 years, although the differences did not reach statistical significance. VEGF level was significantly higher in children with poor metabolic control of the disease (406.65 +/- 322.11 pg/ml vs 132.19 +/- 85.51 pg/ml; p<0.05). Patients with retinopathy had the highest level of VEGF, compared to children without complications. Assessment of VEGF level can be useful method in prognosis of diabetes microangiopathic complications. As microalbuminuria occurs relatively late in diabetic complications process, evaluation of VEGF may become a prognostic marker of the earliest phases of this complication.


Translocation of Photosynthate in Curly Top Virus-infected Tomatoes.
Photosynthate translocation in single leaflets of healthy and curly top virus-infected tomatoes was investigated using (14)C as a marker. The amount of radioactivity found in plant parts not exposed to (14)CO(2) was substantially lower in diseased than in healthy plants. The time lag for the appearance of (14)C in the petiole was considerably longer in the infected plants than in the healthy. The kinetics of disappearance of (14)C from the lamina during the 24-hour period following labeling showed a strong retention of recent assimilates within the diseased leaf, not accompanied by increased immobilization into insoluble forms. Sucrose was the predominant compound participating in photosynthate transport in both healthy and diseased leaves. The amount of (14)CO(2) fixed was approximately 40% lower in curly top virus-infected leaves than in healthy leaves.


Acute liver rejection: evaluation with cell-directed MR contrast agents in a rat transplantation model.
Enhancement patterns with gadolinium (4s)-4-(4-ethoxybenzyl)-3,6,9-tris (carboxylatomethyl)-3,6,9-triazaundecandioic acid (EOB) diethylenetriaminepentaacetic acid (DTPA), a hepatocyte-directed magnetic resonance (MR) contrast agent, and superparamagnetic iron oxide particles (SPIO), a Kupffer cell-directed contrast agent, were compared at MR imaging in rat models of allogeneic and syngeneic liver transplantation. Light and electron microscopy were performed to monitor the morphologic changes in these livers and revealed typical findings in acute rejecting liver (allogeneic transplants) and normal architecture in syngeneic transplants. Liver enhancement with Gd-EOB-DTPA at MR imaging was delayed and prolonged with transplantation, and even more with rejection, but the level of enhancement when compared with that of control rats remained unaffected. Uptake of SPIO was decreased in the acutely rejecting livers but was normal in the syngeneic transplantation model. Enhanced MR imaging with cell-directed contrast agents depicted decreased phagocytotic activity in acute transplant rejection and enabled the excretory function of hepatocytes to be monitored. Additionally, Gd-EOB-DTPA may be applied advantageously for detection of focal lesions in transplanted livers.


Odd-numbered long-chain fatty acids in erythrocyte phospholipids as long-term follow-up parameter in propionic acidemia.
Odd-numbered long-chain fatty acids (OLCFAs) increase in total erythrocyte lipids or plasma in patients with propionic acidemia and have been proposed as a useful parameter of metabolic control. However, up to now no parameter for long-term metabolic control has been available for this disorder. In contrast to previous investigations, we investigated OLCFAs with particular reference to differences for two phospholipid fractions of erythrocyte lipids. The phosphatidylethanolamine (PE) fraction of erythrocyte lipids has a slow turnover rate and might reflect the metabolic propionyl-CoA burden over a period of some weeks. Distinct increases in OLCFA of up to 200% in the phosphatidylcholine fraction were observed after episodes of metabolic decompensation and maximum OLCFA levels were found 3 weeks after the onset of a crisis. As a sign of poor metabolic control, OLCFA levels in PE steadily increased after recurrent episodes of decompensation, but not in clinically stable patients. However, in one patient with clinically good metabolic control, OLCFAs continually increased after the second year of life for an as yet unknown reason. In conclusion, data from this study indicate the usefulness of OLCFA analysis in the PE fraction of erythrocyte lipids, in particular with regard to the need for such a parameter for evidence-based improvement of management strategies in propionic acidemia.


Robust polarimetry via convex optimization.
We present mathematical methods, based on convex optimization, for correcting non-physical coherency matrices measured in polarimetry. We also develop the method for recovering the coherency matrices corresponding to the smallest and largest values of the degree of polarization given the experimental data and a specified tolerance. We use experimental non-physical results obtained with the standard polarimetry scheme and a commercial polarimeter to illustrate these methods. Our techniques are applied in post-processing, which complements other experimental methods for robust polarimetry.


Study on the Effects of EGR and Spark Timing on the Combustion, Performance, and Emissions of a Stoichiometric Natural Gas Engine.
This paper involved conducting an experimental investigation on the effects of exhaust gas recirculation (EGR) and spark timing on the combustion, performance, and emission characteristics of a China-VI heavy-duty, natural gas engine fueled with high-methane content. The results showed that increasing the EGR rate extends the spark timing range and slows the combustion. This then increases ignition delay, prolongs combustion duration, and decreases heat release rate. Peak in-cylinder pressure (PCP) and indicated thermal efficiency (ITE) initially increase because of higher boost pressure with increasing EGR rate. However, as EGR rate increases further, PCP and ITE begin to decrease because of the deviation of combustion phasing. Lower in-cylinder temperature caused by higher EGR rate may cause nitrogen oxide (NOx) emissions to reduce significantly, while total hydrocarbon (THC) and carbon monoxide (CO) emissions increase, and THC emissions could increase exponentially at high EGR rates. In-cylinder pressure, temperature, and heat release rate increase with early spark timing, but the rate of increase is reduced at higher engine speeds. Early spark timing causes THC and CO emissions to increase at part-load conditions, whereas there is little change at full-load conditions. NOx emissions also increase with early spark timing because of the higher in-cylinder temperature.


Stem cell transplantation and lung dysfunction.
To identify factors that impact the incidence and severity of lung dysfunction after haematopoietic stem cell transplantation (HSCT) for preventive and therapeutic purposes. Respiratory failure from lung dysfunction after HSCT is a serious and often fatal transplant-related complication, but recent data reveal decreasing incidence and improving outcome over time. Idiopathic pneumonia syndrome (IPS) and bronchiolitis obliterans are now recognized as part of a spectrum of post-HSCT lung diseases involving both aspects of innate and adaptive immune responses, but may differ in the main lung structure affected: alveolar versus airway epithelium. There exists a strong association between acute graft-versus-host disease (GVHD) and IPS, and bronchiolitis obliterans is pathognomonic of chronic GVHD. Experimental models of IPS and bronchiolitis obliterans have proven useful to test strategies designed to limit lung injury including the effects of allogeneity, chemoradiotherapy and stem cell therapy. Recent advances in critical care practices, early diagnosis and utilizing ARDS Network ventilatory and conservative fluid management recommendations have also contributed to better outcome from lung dysfunction after HSCT. Understanding the factors that contribute to post-HSCT lung injury should lead to safer transplant practices that will allow the broader use of HSCT for sicker children with comorbidities.


Geophysical potential for wind energy over the open oceans.
Wind turbines continuously remove kinetic energy from the lower troposphere, thereby reducing the wind speed near hub height. The rate of electricity generation in large wind farms containing multiple wind arrays is, therefore, constrained by the rate of kinetic energy replenishment from the atmosphere above. In recent years, a growing body of research argues that the rate of generated power is limited to around 1.5 W m-2 within large wind farms. However, in this study, we show that considerably higher power generation rates may be sustainable over some open ocean areas. In particular, the North Atlantic is identified as a region where the downward transport of kinetic energy may sustain extraction rates of 6 W m-2 and above over large areas in the annual mean. Furthermore, our results indicate that the surface heat flux from the oceans to the atmosphere may play an important role in creating regions where sustained high rates of downward transport of kinetic energy and thus, high rates of kinetic energy extraction may be geophysical possible. While no commercial-scale deep water wind farms yet exist, our results suggest that such technologies, if they became technically and economically feasible, could potentially provide civilization-scale power.


Introducing Wound Healing Assays in the Undergraduate Biology Laboratory Using Ibidi Plates.
The wound healing assay is a simple and inexpensive method that allows researchers to experimentally mimic cell growth and migration leading to wound healing. In this assay, a wound is created on a monolayer of cultured mammalian cells and cell migration is monitored. Micrographs are captured at regular intervals during the duration of the experiment. These microscopy images are analyzed to compare cell migration and wound closure under different conditions. Introduction of different cytotoxic treatments into a wound healing assay can provide information as to whether a particular drug or compound of interest has the ability to affect cell migration. This type of analysis is important when assessing the ability of a particular cancer cell line to display invasive and metastatic behaviors. One of the challenges of this assay is to create the original wound in a way that is consistent across plates or treatments, facilitating comparisons across experimental groups. This is a particular challenge when using the wound healing assay in the context of an undergraduate biology class to expose students to a distinct form of mammalian cell culture and help them apply scientific knowledge and research skills. We found an easy way to overcome this obstacle by using ibidi plates. In this article, we provide a simple protocol to use ibidi plates and HeLa cells to set up wound healing assays. This laboratory exercise allows undergraduate students to utilize different skills developed through cell culture experience, such as growing, treating, and imaging mammalian cells.


Bovine immunodeficiency virus: facts and questions.
Bovine immunodeficiency virus (BIV) is a lentivirus whose serologic prevalence is worldwide. Little is known about its impact on animal health status, pathogenesis and mode of transmission. Understanding BIV biology implies isolation of new viral strains and long-term studies on experimentally-infected cows and surrogate hosts such as rabbits.


Cellulose-based functional hydrogels derived from bamboo for product design.
Hydrogels have outstanding research and application prospects in the field of product design. Among them, the design and preparation of cellulose-based functional hydrogels derived from bamboo have attracted increasing research interest. Cellulose-based hydrogels not only have the skeleton function of hydrogels, but also retain excellent specificity, smart structural design, precise molecular recognition ability, and superior biocompatibility. Cellulose-based hydrogels show important application prospects in various fields, such as environmental protection, biomedicine, and energy. What's more, they are potentially viable for application in food packaging and plant agriculture, such as fertilizers release and crop production. Recently, researchers have extracted cellulose from bamboo and generated a variety of cellulose-based functional hydrogels with excellent properties by various cross-linking methods. In addition, a variety of multifunctional hybrid cellulose-based hydrogels have been constructed by introducing functional components or combining them with other functional materials, thus expanding the breadth and depth of their applications. Herein, we elaborate on advances in the field of cellulose-based hydrogels and highlight their applications in food packaging and plant agriculture. Meanwhile, the existing problems and prospects are summarized. The review provides a reference for the further development of cellulose-based hydrogels.


Effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease.
To investigate the effect of theophylline on sleep and sleep-disordered breathing in patients with chronic obstructive pulmonary disease (COPD), we studied 12 male nonhypercapnic subjects with a mean +/- SEM age of 62.8 +/- 2.5 yr and a FEV1 of 1.36 +/- 0.11 L using a randomized double-blind crossover protocol. Sustained-action theophylline (250 mg three times or four times a day) or placebo was administered for 2 days, and the alternate drug was administered on the following 2 days. Sleep studies were performed on Nights 2 and 4 with spirometry at 9:00P.M. and 7:00A.M. Two puffs of metaproterenol or albuterol were administered at 10:00P.M. on both study nights. A theophylline level, drawn at bedtime (10:00 to 11:00P.M.), was 14.2 +/- 0.78 micrograms/ml on the theophylline nights and less than 2 on placebo nights. The morning FEV1 was significantly better during theophylline administration (1.27 +/- 0.12 versus 1.00 +/- 0.11 L, p less than 0.001). The mean arterial oxygen saturation (SaO2) and transcutaneous carbon dioxide pressure (PCO2) were also better during NREM sleep on theophylline nights. Neither the mean SaO2 and transcutaneous PCO2 during REM sleep nor the apnea plus hypopnea index (events per hour of sleep) differed between placebo and theophylline nights. Theophylline administration did not impair the amount or architecture of sleep as neither total sleep time nor the fraction of time spent in Stages 1, 2, and 3/4 and REM differed between the two regimens. The number of arousals per hour of sleep was slightly less on theophylline nights (19.9 +/- 1.7 versus 24.9 +/- 2.7, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Adaptive Cation Pillar Effects Achieving High Capacity in Li-Rich Layered Oxide, Li2 MnO3 -LiMeO2 (Me = Ni, Co, Mn).
Intensive research is underway to further enhance the performance of lithium-ion batteries (LIBs). To increase the capacity of positive electrode materials, Li-rich layered oxides (LLO) are attracting attention but have not yet been put to practical use. The structural mechanisms through which LLO materials exhibit higher capacity than conventional materials remain unclear because their disordered phases make it difficult to obtain structural information by conventional analysis. The X-ray total scattering analysis reveals a disordered structure consisting of metal ions in octahedral and tetrahedral sites of Li layers as a result of cation mixing after the extraction of Li ions. Metal ions in octahedral sites act as rigid pillars. The metal ions move to the tetrahedral site of the Li layer, which functions as a Li-layer pillar during Li extraction, and returns to the metal site during Li insertion, facilitating Li diffusion as an adaptive pillar. Adaptive pillars are the specific structural features that differ from those of the conventional layered materials, and their effects are responsible for the high capacity of LLO materials. An essential understanding of the pillar effects will contribute to design guidelines for intercalation-type positive electrodes for next-generation LIBs.


In vitro comparison of the fracture resistance and failure mode of fiber, ceramic, and conventional post systems at various stages of restoration.
This in vitro study evaluated 6 post systems over 4 simulated clinical stages of tooth restoration to (1) determine quantitatively the fracture resistance strength at each stage when a static loading force is applied to cause failure; (2) determine the failure mode for each post system at each simulated clinical stage; and (3) determine the feasibility of removing failed post systems. Ten post systems made with various materials and designs were tested at the following 4 stages of simulated clinical treatment: stage #1: posts only, loaded using a 3-point loading model to failure, to determine transverse strengths and failure modes for each post system; stage #2: posts alone, bonded into teeth; stage #3: posts bonded into teeth with core build up; stage #4: post and core build up and full veneer restoration. For stages #2 through #4, the coronal portion of 60 mandibular premolars was amputated at the cemento-enamel junction, the canals were treated endodontically, and the specimens were mounted in acrylic blocks. A testing force was applied to the posts at 90 degrees to the long axis of the tooth, 4 mm from the cemento-enamel junction. The O'Brien test for constant variance was performed over the treatment groups. For nonconstant variance, the Welsh analysis of variance was used to test for equalities of treatment means. The Tukey Kramer procedure determined which treatment procedures differed. The failure thresholds for each post system were significantly different at each stage of testing, but the order of test results by post type remained generally consistent from one stage to the next. ParaPosts (Coltene, Whaledent Int, New York, NY) and core build up resulted in significantly higher failure thresholds through all 4 stages of testing. This post system also consistently displayed a high number of nonfavorable tooth fractures. FibreKor post and cores (Jeneric Pentron Inc, Wallingford, CT) resulted in significantly lower failure threshold values in stages #2 through #4. This post system displayed no tooth fractures in stages #2 and #3 and a similar number of nonfavorable tooth fractures in stage #4 when compared with the other systems. C-Post (Bisco Dental Products, Schaumburg, IL), CosmoPost (Ivoclar Vivadent North America Inc, Amherst, NY), and AesthetiPost (Bisco Dental Products) grouped in descending order through stages #2 to #4. These systems displayed intermediate fracture resistance strengths, as well as a moderate number of nonfavorable tooth fractures. CosmoPost exhibited a significant number of brittle post fractures with fragments left in the root canal at all stages. The fracture resistance of the cast metal post varied from stage to stage. No teeth fractured at stage #2. At stage #3, 9 of 10 teeth fractured nonfavorably, and all teeth fractured nonfavorably in stage #4. The fiber posts evaluated provided an advantage over a conventional post that showed a higher number of irretrievable post and unrestorable root fractures. At the stage of final restoration insertion, there was no difference in force to failure for all but the FibreKor material, which continued to be weaker than all other tested materials. The fiber posts were readily retrievable after failure, whereas the remaining post systems tested were nonretrievable. J Prosthodont 2001;10:26-36.


Melatonin and its relationship to plant hormones.
Plant melatonin appears to be a multi-regulatory molecule, similar to those observed in animals, with many specific functions in plant physiology. In recent years, the number of studies on melatonin in plants has increased significantly. One of the most studied actions of melatonin in plants is its effect on biotic and abiotic stress, such as that produced by drought, extreme temperatures, salinity, chemical pollution and UV radiation, among others. This review looks at studies in which some aspects of the relationship between melatonin and the plant hormones auxin, cytokinin, gibberellins, abscisic acid, ethylene, jasmonic acid and salicylic acid are presented. The effects that some melatonin treatments have on endogenous plant hormone levels, their related genes (biosynthesis, catabolism, receptors and transcription factors) and the physiological actions induced by melatonin, mainly in stress conditions, are discussed. Melatonin is an important modulator of gene expression related to plant hormones, e.g. in auxin carrier proteins, as well as in metabolism of indole-3-acetic acid (IAA), gibberellins, cytokinins, abscisic acid and ethylene. Most of the studies performed have dealt with the auxin-like activity of melatonin which, in a similar way to IAA, is able to induce growth in shoots and roots and stimulate root generation, giving rise to new lateral and adventitious roots. Melatonin is also able to delay senescence, protecting photosynthetic systems and related sub-cellular structures and processes. Also, its role in fruit ripening and post-harvest processes as a gene regulator of ethylene-related factors is relevant. Another decisive aspect is its role in the pathogen-plant interaction. Melatonin appears to act as a key molecule in the plant immune response, together with other well-known molecules such as nitric oxide and hormones, such as jasmonic acid and salicylic acid. In this sense, the discovery of elevated levels of melatonin in endophytic organisms associated with plants has thrown light on a possible novel form of communication between beneficial endophytes and host plants via melatonin.


The pediatric spica cast: a sex-related modification.
For the child's comfort and to facilitate nursing care, placement of the supporting strut on a hip spica is posterior for the male and anterior for the female.


Influence of cycle exercise on acetone in expired air and skin gas.
This study investigated the influence of cycle exercise on acetone concentration in expired air and skin gas. The subjects for this experiment were eight healthy males. Subjects performed a continuous graded exercise test on a cycle ergometer. The workloads were 360 (1.0 kg), 720 (2.0 kg), 990 (2.75 kg) kgm/min, and each stage was 5 min in duration. A pedaling frequency of 60 rpm was maintained. Acetone concentration was analyzed by gas chromatography. The acetone concentration in expired air and skin gas during exercise at 990 kgm/min intensity was significantly increased compared with the basal level. The skin-gas acetone concentration at 990 kgm/min significantly increased compared with the 360 kgm/min (P < 0.05). The acetone excretion of expired air at 720 kgm/min and 990 kgm/min significantly increased compared with the basal level (P < 0.05). Acetone concentration in expired air was 4-fold greater than skin gas at rest and 3-fold greater during exercise (P < 0.01). Skin gas acetone concentration significantly related with expired air (r = 0.752; P < 0.01). This study confirmed that the skin-gas acetone concentration reflected that of expired air.


Thymocyte-synthesized glucocorticoids play a role in thymocyte homeostasis and are down-regulated by adrenocorticotropic hormone.
Thymocytes from adult mice synthesize glucocorticoids (GCs), and some data indicate a role for this hormone production in thymic homeostasis. Here we present further support for this view by showing that the dramatic increase in thymocyte number seen after adrenalectomy (ADX) does not correlate with the decrease in systemic GCs but rather with an ACTH-mediated down-regulation of GC synthesis in thymocytes. High ACTH concentrations caused by ADX in wild-type mice down-regulated CYP11B1 mRNA expression, encoding the last enzyme required for corticosterone synthesis and as a consequence reduced GC synthesis in thymocytes. This was not seen in IL-1beta/IL-18 double-knockout mice unable to respond to ADX with high ACTH levels. However, if ADX IL-1beta/IL-18 double-knockout mice were treated with ACTH, this led to a down-regulation of CYP11B1 and GC synthesis in thymocytes. In addition, in vivo treatment of mice with the CYP11B1 antagonist metyrapone, without affecting the systemic corticosterone level, increased thymocyte numbers and in vitro treatment of isolated thymocytes prevented thymocyte loss. Furthermore, in vitro experiments showed that both ACTH and its receptor-induced second-messenger molecule cAMP down-regulated mRNA expression of critical enzymes in GC steroidogenesis and GC synthesis in thymocytes. We conclude that thymocyte-produced GCs are important for the homeostasis of adult mouse thymocytes and that high ACTH level, in contrast to stimulating GC synthesis in the adrenal glands, has the opposite effect in thymocytes.


[Relationship between activity of hydrolases in fungi isolated from vagina of pregnant women and selected symptoms].
Pregnancy is considered a factor of vulvovaginal mycosis. Secretion of hydrolases is an important determinant of Candida virulence. Thus, the aim of the study was to found the relationship between activity of 19 hydrolases in fungi isolated from vagina of pregnant women and symptoms of mycosis. 251 pregnant women were examined. Samples were collected from vagina and cultured on Sabouraud media. Activity of hydrolytic enzymes was evaluated using API ZYM (bioMerieux) test Fungi were found in 20.1% of vaginal samples. Symptoms were detected in 45.8% of women. Only 32.1% of women with discharge and 26.4% with pruritus had mycosis. Out of the 19 examined hydrolazes, 13 active enzymes were detected in fungal strains. We found for the first time the relationship between activity of fungal esterase lipase and the presence of vaginal discharge in pregnant women.


Antimicrobial activities of microbial strains isolated from soil of stressed ecological niches of Eastern Uttar Pradesh, India.
Antimicrobial activities of twenty bacterial strains isolated from ten different stressed agro-ecological niches of Eastern Uttar Pradesh, India were evaluated against bacteria, yeasts and molds. Eleven isolates showing strong antimicrobial activities were characterized. Eight antifungal compounds were purified and partially characterized by Ultra-Violet (UV) absorption spectra and grouped into polyenes and non-polyenes. Antibacterial metabolites produced by four isolates were purified and chemically characterized, of which one isolate (AB) produced a new form of olivanic acid, and other three isolates (C5, Py and M4) produced antibacterial compounds having phenoxazone nucleus.


Alprazolam-induced mania: two clinical cases.
Two patients treated with alprazolam had histories suggestive of a bipolar disorder and developed lithium-responsive manic episodes. The authors caution that treatment with alprazolam may be complicated by the induction of mania.


Increase in paratyphoid fever cases in Japanese travellers returning from Cambodia in 2013.
In 2013, an unusual increase of paratyphoid fever cases in travellers returning from Cambodia was reported in Japan. From December 2012 to September 2013, 18 cases of Salmonella Paratyphi A infection were identified. Microbiological analyses revealed that most isolates had the same clonal identity, although the epidemiological link between these cases remains unclear. It was inferred that the outbreak was caused by a common and persistent source in Cambodia that was likely to have continued during 2014. The information of surveillance and laboratory data from cases arising in travellers from countries with limited surveillance systems should be timely shared with the country of origin.


Caecal threadworms Trichostrongylus tenuis in red grouse Lagopus lagopus scoticus: effects of weather and host density upon estimated worm burdens.
Trichostrongylus tenuis eggs were counted in faeces from individually marked wild red grouse for 8 years. Egg counts varied seasonally and annually. In some years, a sudden increase in mid-April was consistent with delayed maturation of larvae which had overwintered in the birds in a hypobiotic state. A more gradual increase in summer was probably due to uninterrupted maturation of larvae ingested then. Despite 30-fold year-to-year variation in mean egg counts, relative differences in egg counts among known individuals within years tended to persist across years. Rainfall in previous summers explained much of the year-to-year variation in egg counts, probably because parasite recruitment was greatest during wet summers. Grouse density was only weakly related to worm egg counts. The data were not consistent with the hypothesis that the cyclic-type population fluctuation in red grouse numbers observed at the time of this study was caused by the parasites.


Molecular modeling of flavonoids that inhibits xanthine oxidase.
The inhibition of xanthine oxidase activity by various flavonoids was assessed. All of the tested flavonoids were competitive inhibitors, and from the kinetic analysis suggested that flavonoids bind to the reactive site. To further understand the stereochemistry between these flavonoids and xanthine oxidase, structure-based molecular modeling was performed. Apigenin was the most potent inhibitor which showed the most favorable interaction in the reactive site. The bicyclic benzopyranone ring of apigenin stacked with phenyl of Phe 914, and the phenolic group stretched to the space surrounding with several hydrophobic residues. Quercetin and myricetin composed a 3-hydroxyl group on benzopyranone which resulting in reduction of binding affinity. The phenolic group of genistein positioned in opposite orientation comparison with apigenin, and resulted in a weaker interaction with xanthine oxidase. Isovitexin showed the weakest inhibitory effect among the compounds tested. The bulky group of sugar in isovitexin may hamper its interaction with xanthine oxidase.


Burn injury with infection alters prostaglandin E2 synthesis and metabolism.
The aim of this study was to examine the relationship between prostaglandin synthesis and prostaglandin degradation in a model of burn injury with infection. Male B2D6F1 mice were assigned to control, burn (16% dorsal scald burn), or burn with infection (burn with topical application of 1,000 colony forming units of Pseudomonas aeruginosa) groups. Lung tissue was harvested at 1, 2, and 3 days after burn injury and subsequently processed for total RNA and protein. Northern and Western blot analyses were used to examine differences in cyclooxygenase 2 (COX-2) and prostaglandin 15-OH dehydrogenase (PGDH) protein and mRNA expression. Total RNA was probed with the riboprobe for murine PGDH and COX-2 and the 100,000g protein fraction was immunoblotted by using an rabbit anti-murine PGDH and anti-murine COX-2 antibody. COX-2 expression was elevated in the burn with infection animals on day 1 and day 2 after burn injury. At these time points in the burn + infection group, PGDH was significantly depressed. Burn injury increased COX-2 expression on day 1, but by day 2, COX-2 expression had decreased to control values. A corresponding increase in PGDH expression was observed on day 2 in the burned mice. The mRNA expression of COX-2 was followed by a similar increase in COX-2 protein expression at all time points in the injured animals. This was not the case with PGDH expression. On day 1, PGDH mRNA expression was depressed in the burn with infection mice with no change in PGDH protein expression. This finding indicates that PGDH is subject to regulation at both the transcriptional and posttranscriptional levels. Burn wound infection depressed both PGDH mRNA and protein expression and increased COX-2 mRNA and protein expression. Therefore, increases in circulating prostaglandin E2 levels during septic injury are derived from alterations in synthesis and degradation of prostaglandin E2.


Combined use of MS-222 (tricaine) and isoflurane extends anesthesia time and minimizes cardiac rhythm side effects in adult zebrafish.
As an important vertebrate model organism, zebrafish are typically studied at the embryonic stage to take advantage of their properties of transparency and rapid development. However, more and more studies require assays to be done on adults. Consequently, a good anesthetic is needed to sedate and immobilize the adult zebrafish during experimental manipulation. To date, MS-222 (tricaine methanesulfonate) is the only Food and Drug Administration approved anesthetic for aquaculture and is widely used by the zebrafish research community. Nevertheless, in adult zebrafish, MS-222 reduces heart rate and causes high mortality under long-term sedation. Consequently, adult zebrafish have limited research applications. In this study, we present a new anesthetic formula for the adult zebrafish that results in minimal side effects on its physiology under prolonged sedation. The combined use of MS-222 with isoflurane effectively extended the time of anesthesia, and the zebrafish recovered faster than when anesthetized with the traditional MS-222. Moreover, MS-222 + isoflurane did not cause reduction of heart rates, which enabled long-term electrocardiogram recording and microscopic observation on the adult zebrafish. Taken together, the new MS-222 + isoflurane formula will facilitate general applications of adult zebrafish in time-consuming experiments with minimal side effects on the model organism's overall physiology.


Isotopic analysis of dissolved organic nitrogen in soils.
Determination of the isotopic signature of dissolved organic nitrogen (DON) is important to assess its dynamics in terrestrial ecosystems. Analysis of (15)N-DON, however, has been hindered by the lack of simple, reliable, and established methods. We evaluate three off-line techniques for measuring the (15)N signature of DON in the presence of inorganic N using a persulfate digestion followed by microdiffusion. The (15)N-DON signature is calculated from the difference between total dissolved (15)N ((15)N-TDN) and inorganic (15)N. We quantified the (15)N recovery and signature of DON, NH(4)(+), and NO(3)(-) in a series of inorganic N/DON mixtures (with a TDN concentration of 10 mg N L(-1)) for three lab protocols. Phenylalanine was used as a model compound for DON. The best lab protocol determined the concentration of inorganic N and TDN prior to diffusion using improved spectrophotometric techniques. An accuracy of 88% for (15)N-DON should be routinely possible; coefficient of variation was <2.9%. Hence, reliable (15)N-DON values are obtained over an DON concentration range of 2.3-10 mg L(-1). High levels of DON could influence the accuracy of (15)N-NO(3)(-) mainly at DON:NO(3)(-) ratios above 0.4. Evaluation of alternative NO(3)(-) measurements is still necessary. Our method is applicable for soil solution samples and soil extracts and has no risk of cross-contamination. Potential applications are large, in particular for (15)N tracer studies, and will increase our insight in DON behavior in soils.


Early outcomes of percutaneous pulmonary valve implantation using the Edwards SAPIEN XT transcatheter heart valve system.
Patients with congenital or acquired heart defects affecting the pulmonary valve and right ventricular outflow tract (RVOT) commonly require multiple surgical interventions, resulting in significant morbidity. A less invasive alternative is percutaneous pulmonary valve implantation (PPVI). Though studies have previously reported the safety and efficacy of the early generation transcatheter heart valves (THVs), data on more recent devices are severely lacking. We performed a multinational, multicentre, retrospective, observational registry analysis of patients who underwent PPVI using the Edwards SAPIEN XT THV. Of the 46 patients that were enrolled, the majority had tetralogy of Fallot as the underlying diagnosis (58.7%), and stentless xenograft as the most common RVOT anatomy (34.8%). Procedural success rate was high (93.5%), with a low frequency of periprocedural complications and adverse events (6.5% and 10.9%, respectively). At 30days post-procedure, NYHA class had improved significantly (90.6% were at NYHA I or II). The rate of moderate/severe pulmonary regurgitation had decreased from 76.1% at baseline to 5.0% at 30days, and the calculated peak systolic gradient had decreased from 45.2 (SD±21.3) mmHg to 16.4 (SD±8.0) mmHg, with these values remaining low up to 2years. The data suggest the efficacy and safety of the SAPIEN XT THV in PPVI in common anatomies in patients with conduits, as well as those with native pulmonary valves or transannular patches. Continued data collection is necessary to verify long-term findings. CLINICALTRIALS. NCT02302131.


Sympathetic innervation of fetal mouse thymus.
This study was carried out to investigate the presence of sympathetic nerve fibers in the developing thymus. Thymic rudiments from 13 days of gestation up to birth and adult thymuses were examined by histofluorescence microscopy to detect the presence of these nerve fibers during ontogeny. Sympathetic nerve fibers were first visible around day 17 of gestation and increased in density and distribution by the time of birth and in the adult thymus. The appearance of immunoreactive cells about the same time as the presence of nerve fibers in the thymic rudiments has been discussed in light of a regulatory role for the sympathetic neuronal input on the maturation of thymocytes during ontogeny.


Mucosal immunity in the female genital tract, HIV/AIDS.
Mucosal immunity consists of innate and adaptive immune responses which can be influenced by systemic immunity. Despite having been the subject of intensive studies, it is not fully elucidated what exactly occurs after HIV contact with the female genital tract mucosa. The sexual route is the main route of HIV transmission, with an increased risk of infection in women compared to men. Several characteristics of the female genital tract make it suitable for inoculation, establishment of infection, and systemic spread of the virus, which causes local changes that may favor the development of infections by other pathogens, often called sexually transmitted diseases (STDs). The relationship of these STDs with HIV infection has been widely studied. Here we review the characteristics of mucosal immunity of the female genital tract, its alterations due to HIV/AIDS, and the characteristics of coinfections between HIV/AIDS and the most prevalent STDs.


Platelet transfusion support for patients with cancer and hematologic malignancies.
Advances in platelet transfusion have contributed to improved outcomes in the treatment of patients with cancer and leukemia. However, the optimal strategies to avoid some of the side effects that could result from platelet transfusions remain under investigation. These side effects include the development of refractoriness to transfusions, alloimmunization, transfusion reactions, the transmission of infectious agents, and transfusion-associated graft-versus-host disease. Leukodepletion by filtration is promising as a means of preventing the development of alloimmunization. Results of the Trial to Reduce Alloimmunization to Platelets will be reported shortly and will shed more light on that issue. Bedside filtration of cellular blood products also diminishes the transmission of cytomegalovirus infections by that route. Transfusion reactions are often mediated by cytokines in the plasma fraction of transfused platelet concentrates, and leukodepletion prior to storage reduces their incidence. Serious bacterial infections are sometimes transmitted by platelet transfusions and improved methods are needed for their detection and prevention. Photochemical methods that could inactivate bacteria and viruses in contaminated products deserve further study.


Phylogeographic and population genetic analyses reveal Pleistocene isolation followed by high gene flow in a wide ranging, but endangered, freshwater mussel.
Freshwater organisms of North America have had their contemporary genetic structure shaped by vicariant events, especially Pleistocene glaciations. Life history traits promoting dispersal and gene flow continue to shape population genetic structure. Cumberlandia monodonta, a widespread but imperiled (IUCN listed as endangered) freshwater mussel, was examined to determine genetic diversity and population genetic structure throughout its range. Mitochondrial DNA sequences and microsatellite loci were used to measure genetic diversity and simulate demographic events during the Pleistocene using approximate Bayesian computation (ABC) to test explicit hypotheses explaining the evolutionary history of current populations. A phylogeny and molecular clock suggested past isolation created two mtDNA lineages during the Pleistocene that are now widespread. Two distinct groups were also detected with microsatellites. ABC simulations indicated the presence of two glacial refugia and post-glacial admixture of them followed by simultaneous dispersal throughout the current range of the species. The Ouachita population is distinct from others and has the lowest genetic diversity, indicating that this is a peripheral population of the species. Gene flow within this species has maintained high levels of genetic diversity in most populations; however, all populations have experienced fragmentation. Extirpation from the center of its range likely has isolated remaining populations due to the geographic distances among them.


FDA Seeks Tighter Restrictions on E-cigarettes.
The FDA recently announced a plan to combat underage use of nicotine products by targeting flavors that appeal to adolescents. The proposal outlines restrictions on sales of flavored cartridges for electronic cigarettes, and a ban on menthol-flavored combustible cigarettes and all flavored cigars.


Appearance of circularly polarized light in an atmosphere-ocean system.
Using a Monte Carlo algorithm to simulate the scattering of sunlight in an atmosphere-ocean system, the degree of circular polarization of light in the ocean has been calculated at multiple depths and directions. In this system circularly polarized light is produced by the reflection of light from beneath the surface at an incident angle greater than the critical angle. We present the results of these simulations for different solar angles, wavelengths of light, and models that include the presence of aerosols in the atmosphere and hydrosols in the water.


Environmental enrichment facilitates amygdala kindling but reduces kindling-induced fear in male rats.
The purpose of this experiment was to determine the effect of prior environmental enrichment on the acquisition of kindling and the expression of kindling-induced fear. Sixty male rats were housed either in an enriched environment or in isolation, starting immediately after weaning. As adults, they were subjected to either 50 amygdala-kindling stimulations or sham stimulations, followed by testing in an unfamiliar open field. The kindled-enriched rats acquired the kindled state more quickly than did the kindled-isolated rats, but they also showed less fear in the open field than did the kindled-isolated rats. These results suggest that environmental enrichment has differential effects on kindling acquisition and its behavioral consequences.


Outcomes, risk factors and health burden of contrast-induced acute kidney injury: an observational study of one million hospitalizations with image-guided cardiovascular procedures.
Despite the use of low-osmolar contrast media that have significantly reduced the occurrence of severe adverse reactions, contrast-induced (CI) acute kidney injury (AKI) remains the third cause of AKI in hospitals. We sought to estimate the frequency of CI-AKI among hospitalized patients undergoing image-guided cardiovascular procedures, to quantify the effect of risk factors on the development of this complication and to assess relative organizational and economic burden in healthcare. A retrospective cross-sectional population-based study using the extensive French hospital discharge database (PMSI) was carried out. Hospitalizations with image-guided cardiovascular procedures using a contrast media were identified in adults over a 2-year period (2012-2013). Suspected CI-AKI was defined as the presence, during hospitalization, of a diagnostic code of AKI (International Classification of Diseases, 10th revision [ICD-10] codes: N141, 142, N144, N990, N17, N19 or R392) or a code of renal replacement therapy procedure (Classification Commune des Actes Médicaux [CCAM] codes: JVJB001, JVJF002-005 and JVJF008) as creatinine criteria were not available. During 1,047,329 hospitalizations studied, 32,308 suspected CI-AKI were observed, yielding a frequency of 3.1 %. By multivariate analysis, factors that significantly increased the risk of suspected CI-AKI included cardiogenic shock (odds ratio [OR] = 20.5, 95 % confidence interval [95 % CI] [18.7; 22.5]), acute heart failure (OR = 2.5, 95 % CI [2.4; 2.6]) and chronic kidney disease (OR = 2.3, 95 % CI [2.2; 2.3]. Renal replacement therapy was initiated during 6,335 (0.6 %) hospitalizations. The mean length of stay and cost of hospitalizations associated with suspected CI-AKI was higher than in hospitalizations without suspected CI-AKI (20.5 vs 4.7 days, p < 0.00001 and €15,765 vs €3,352, p < 0.0001, respectively). This is the first large-scale population-based study to estimate frequency and health burden of suspected CI-AKI occurring after image-guided cardiovascular procedures, and the first available data in a French population. We showed that this iatrogenic complication remains of high concern despite prevention efforts and contrast media product improvement. From our results, suspected CI-AKI is associated with particularly high mortality, significantly extends hospitalizations, and leads to additional costs reaching a total of €200M per year.


[Examination about the influence for daily life that nail and skin disorders induced by docetaxel in patients with breast cancer].
Docetaxel is one of the most important chemotherapeutic agents for the breast cancer patients. However, it has also experienced as toxicities causing nail diformation and skin trouble, and is considered as adverse elements other than edema and neurotoxicity. It is expected to have tremendous influence on women's daily life-decrease in quality of life. Nail and skin toxicity might occur among patients treated with docetaxel more frequently than evidence in the clinical medical records. Therefore, we have conducted a questionnaire investigation, targeting the patients who had been treated with docetaxel. Between March, 2004 and February, 2006, 52 patients, who had been prescribed docetaxel at the time of the surgery, or for their relapse, became subject to the evaluation. Skin impediments have found most during the second and the third courses; the contents include discomfort towards their beauty and housework. Influence to their daily life that the patients feel do not necessarily match the contents that doctors have recognized. In conclusion, this investigation evidenced that the troubles on quality of life such as nail and skin troubles, should be paid more attention, as well as major side effects such as edema, neutropenia, and neurotoxicity.


Two cases of disseminated mucormycosis in patients following allogeneic bone marrow transplantation.
We describe two cases of disseminated mucormycosis following allogeneic bone marrow transplantation (BMT). Both patients were suffering from chronic graft-ver-sus-host disease (GVHD) and treated with prolonged administration of corticosteroid. In both cases, the initial symptoms were high fever and left flank pain. Involved organs were the spleen, right kidney and the right lung in one case, and the spleen and the brain in the other. The diagnosis was confirmed by pathology after splenectomy. One patient, in whom the immunosuppressants could be discontinued, was treated with prolonged conventional and liposomal amphotericin B and 5-fluorocytosine. The other, in whom the immunosuppressants could not be discontinued due to extensive GVHD, was unresponsive to amphotericin B, and eventually died from the fungal infection. Although mucormycosis, especially the disseminated form thereof is infrequent, it should be considered in high-risk patients because early diagnosis and timely therapy combining antifungal drug or surgery and reduction of immunosuppression appear to improve the prognosis.


Detrended partial cross-correlation analysis of two nonstationary time series influenced by common external forces.
When common factors strongly influence two power-law cross-correlated time series recorded in complex natural or social systems, using detrended cross-correlation analysis (DCCA) without considering these common factors will bias the results. We use detrended partial cross-correlation analysis (DPXA) to uncover the intrinsic power-law cross correlations between two simultaneously recorded time series in the presence of nonstationarity after removing the effects of other time series acting as common forces. The DPXA method is a generalization of the detrended cross-correlation analysis that takes into account partial correlation analysis. We demonstrate the method by using bivariate fractional Brownian motions contaminated with a fractional Brownian motion. We find that the DPXA is able to recover the analytical cross Hurst indices, and thus the multiscale DPXA coefficients are a viable alternative to the conventional cross-correlation coefficient. We demonstrate the advantage of the DPXA coefficients over the DCCA coefficients by analyzing contaminated bivariate fractional Brownian motions. We calculate the DPXA coefficients and use them to extract the intrinsic cross correlation between crude oil and gold futures by taking into consideration the impact of the U.S. dollar index. We develop the multifractal DPXA (MF-DPXA) method in order to generalize the DPXA method and investigate multifractal time series. We analyze multifractal binomial measures masked with strong white noises and find that the MF-DPXA method quantifies the hidden multifractal nature while the multifractal DCCA method fails.