Ecotoxicity assessment of triphenyl phosphate (TPhP) exposure in Hoplobatrachus rugulosus tadpoles.
Triphenyl phosphate (TPhP), a widely used aromatic organophosphate flame retardant, is known to accumulate in organisms through water, air, and soil, consequently, causing toxicity. This study is the first to evaluate the acute and sub-chronic toxicities of TPhP to amphibians. In the acute toxicity analysis, the 96-h median lethal concentration (LC50) for GS35 Hoplobatrachus rugulosus tadpoles was 2.893 mg/L, and the 10% effect concentration (EC10) was 289 μg/L. After two weeks of exposure to low TPhP concentrations, the survival and metamorphosis rates of H. rugulosus tadpoles decreased, and the metamorphosis time was prolonged as the TPhP concentration increased. The threshold concentration that affected tadpole survival and metamorphosis time was 50 μg/L and 100 μg/L, respectively. No significant differences were observed in the condition factor and hepatic somatic index of the tadpole after metamorphosis; however, tadpole body mass and TPhP concentration were negatively correlated. Further, TPhP inhibited the expressions of Cu-Zn sod and cat, thereby reducing the activities of superoxide dismutase and catalase in the tadpole liver. The threshold for affecting gene expression and enzymatic activity was 100 μg/L. These findings provide significant insights on the stress ecology of aquatic organisms.


Algorithms for using an activity-based accelerometer for identification of infant sleep-wake states during nap studies.
To determine the accuracy of using different algorithms on the output from an Actical accelerometer, a device normally used to measure physical activity, to distinguish sleep from wake states. Thirty-one infants aged 10-22 weeks wore the accelerometer on the shin for a daytime nap recording in tandem with polysomnography. Sleep-wake epochs were identified using four computations/algorithms: the zero-threshold computation, two common algorithms used for wrist-based devices (Sadeh and Cole), and a new algorithm developed for this study (count-scaled). Accuracy was examined in direct epoch comparison with polysomnography using 15-, 30- and 60-s sampling epochs. Overall agreements (accuracy) for sleep-wake states were >80% for all computations. The count-scaled algorithm sampling 15-s epochs gave the highest accuracy, with sensitivity (sleep agreement) at 86% and specificity (awake agreement) at 85%. Other computations yielded higher sensitivity at the expense of specificity. Another way to assess the accuracy of identification of sleep-wake states was to compare sleep parameter outputs. All computations and sampling epochs were significantly correlated with total sleep time (r=0.76-0.88), sleep latency (r=0.70-0.93), sleep efficiency (r=0.76-0.87), and wake time after sleep onset (r=0.41-0.53). The number of awakenings after sleep onset was overestimated by accelerometry. The Actical accelerometer, designed to measure physical activity, can reliably identify sleep in infants during napping, with the count-scaled algorithm showing some advantages over other methods for accurate identification of sleep-wake epochs.


Leveen shunt visualization without function using technetium-99m macroaggregated albumin.
Nonfunction of a Leveen shunt was diagnosed in a 53-year-old cirrhotic woman by lack of lung visualization following intraperitoneal administration of Tc-99m MAA, despite imaging of the shunt tubing itself. Surgery confirmed the malfunction and follow-up study after surgical correction showed normal function. Using intraperitoneal injection, an end-organ must be seen to confirm shunt function. The method of Rosenthall et al may provide a more rapid diagnosis of nonfunction without the necessity of end-organ imaging.


A case report of secondary parathyroid adenomatous hyperplasia with carcinoma.
Secondary parathyroid hyperplasia canceration is very rare and thus easily be overlooked during parathyroid ultrasound examination. However, secondary parathyroid hyperplasia still has the possibility of canceration, and it is still important to be alert to its occurrence when performing ultrasound examinations and clinical treatment. A 49-years-old man visited our outpatient department with generalized weakness and pain in both lower extremities a month ago. Hyperparathyroidism secondary to chronic renal failure. The patient underwent ultrasound and other preoperative examinations. The preoperative ultrasound showed 3 parathyroid enlargements, 2 on the left and 1 on the right. The patient then underwent surgical treatment. Ultrasonography suggested the presence of 3 parathyroid hyperplasias, and ectopic right inferior parathyroid gland was visible during intraoperative examination. 10 days after surgery, the patient's Parathyroid Hormone returned to the normal range. Secondary parathyroid hyperplasia has the potential to become cancerous, so doctors should be alert to its occurrence when conducting ultrasound examinations. Ultrasound examination is the key to its diagnosis and subsequent treatment.


A population-based study on serious inpatient bacterial infections in patients with chronic lymphocytic leukemia and their impact on survival.
Infections in chronic lymphocytic leukemia (CLL) have been thoroughly investigated in the setting of clinical trials and single-center studies. However, large cohort studies on real-world data and studies on temporal trends are lacking. We performed a nationwide study on serious bacterial infections in CLL. Using high-quality Swedish government-based registries, 13 009 CLL patients diagnosed in 1982-2013 and their 49 380 matched controls were included. Overall, CLL patients had an increased risk of serious inpatient bacterial infections with a hazard ratio (HR) 5.32 and 95% confidence interval (95% CI) 5.11-5.53, and the highest risk was observed for septicemia (HR 6.91, 95% CI 6.46-7.39) and lung infections (5.91, 5.64-6.18). The risk of serious inpatient bacterial infections decreased overtime with HR 0.87 (0.81-0.94) and HR 0.76 (0.70-0.82) in 1993-2002 and 2003-2013, respectively, compared to 1982-1992. CLL patients had an increased risk of death following a serious inpatient bacterial infection compared to matched CLL patients, and the risk was highest in the first 12 months after the infection (HR 5.48, 95% CI 5.11-5.90). We have, in this nationwide study, characterized the risk of serious bacterial infections in CLL patients and, importantly, depicted that the risk has decreased overtime.


MicroRNAs in somatic cell reprogramming.
The generation of induced pluripotent stem (iPS) cells by exogenous transcription factors involves a comprehensive rearrangement of cellular functions, including the microRNA profile. The resulting cell lines are similar to embryonic stem (ES) cells and have therefore raised much interest for in vitro studies and the perspective of clinical application. Yet, microRNAs are not mere listeners of the reprogramming orchestra but play an active role in the process. In consequence, overexpression or suppression of individual microRNAs has profound effects in colony formation efficiency, and in combination they can produce iPS cells without added transcription factors. Moreover, variations in microRNA expression of iPS/ES cells can predict their differentiation potential and may have consequences at other levels. Altogether, these findings highlight the relevance of pursuing further these studies.


Calibration of intracellular Ca transients of isolated adult heart cells labelled with fura-2 by acetoxymethyl ester loading.
A procedure for calibration of fluorescence signals from adult rat heart cells loaded with the -AM ester of fura-2 is described. Calibration is complicated by dye compartmentation and potentially incomplete dye hydrolysis. These problems were overcome by subtracting from fluorescence transients the non-cytosolic (mitochondrial) component of fura-2 fluorescence plus any Ca-insensitive component of dye fluorescence, after selectively and sequentially quenching cytosolic and non-cytosolic dye with Mn. The Kd of fura-2 in cells loaded by the -AM ester, in cells depleted of ATP and equilibrated with Ca buffers, was found to be 371 +/- 39 nM at 37 degrees C. We found that calibration values for RMAX and RMIN derived from previously measured cells were of general validity, removing the need to measure RMAX and RMIN on every cell. Once these calibration values are determined, the calibration procedure to measure cytosolic Ca on any cell is a five minute procedure to determine compartmentation, using just one non-toxic and inexpensive solution. Finally, we have calculated how the errors intrinsic to the measurements translate into errors of the calculated Ca concentration and transient peak heights. These calculations allow reasonable parameters for data acquisition to be set.


Primary angiitis of the central nervous system presenting with subacute and fatal course of disease: a case report.
Primary angiitis of the central nervous system is an idiopathic disorder characterized by vasculitis within the dural confines. The clinical presentation shows a wide variation and the course and the duration of disease are heterogeneous. This rare but treatable disease provides a diagnostic challenge owing to the lack of pathognomonic tests and the necessity of a histological confirmation. A 28-year-old patient presenting with headache and fluctuating signs of encephalopathy was treated on the assumption of viral meningoencephalitis. The course of the disease led to his death 10 days after hospital admission. Postmortem examination revealed primary angiitis of the central nervous system. Primary angiitis of the central nervous system should always be taken into consideration when suspected infectious inflammation of the central nervous system does not respond to treatment adequately. In order to confirm the diagnosis with the consequence of a modified therapy angiography and combined leptomeningeal and brain biopsy should be considered immediately.


Dysfunctional stress responses in chronic pain.
Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints.


Animal carcass burial management: implications for sustainable biochar use.
This review focuses on existing technologies for carcass and corpse disposal and potential alternative treatment strategies. Furthermore, key issues related to these treatments (e.g., carcass and corpse disposal events, available methods, performances, and limitations) are addressed in conjunction with associated environmental impacts. Simultaneously, various treatment technologies have been evaluated to provide insights into the adsorptive removal of specific pollutants derived from carcass disposal and management. In this regard, it has been proposed that a low-cost pollutant sorbent may be utilized, namely, biochar. Biochar has demonstrated the ability to remove (in)organic pollutants and excess nutrients from soils and waters; thus, we identify possible biochar uses for soil and water remediation at carcass and corpse disposal sites. To date, however, little emphasis has been placed on potential biochar use to manage such disposal sites. We highlight the need for strategic efforts to accurately assess biochar effectiveness when applied towards the remediation of complex pollutants produced and circulated within carcass and corpse burial systems.


Hypothyroidism Modeling in Wistar Rats: Comparison of Two Surgical Methods.
In this study we present 2 surgical models of hypothyroidism in male Wistar rats (n=80) based on total thyroidectomy. Animals weighing 180-200 g were randomly divided into sham-operated group and 2 experimental groups. Thyroidectomy was performed by 2 different methods: primary ligation of either thyroid artery (TE-I) or vein (TE-II). The success of the model was verified through general postoperative conditions, serum hormone levels, histological study, and neck ultrasound. Hypothyroidism was successfully reproduced in both TE-I and TE-II models. TE-I was characterized by lower intra- and post-operative mortality, while TE-II provided better surgical exposure to the key anatomical sites.


New thermodynamically consistent competitive adsorption isotherm in RPLC.
A new equation of competitive isotherms was derived in the framework of the ideal adsorbed solution (IAS) that predicts multisolute adsorption isotherms from single-solute isotherms. The IAS theory makes this new isotherm thermodynamically consistent, whatever the saturation capacities of these single-component isotherms. On a Kromasil-C(18) column, with methanol-water (80/20 v/v) as the mobile phase, the best single-solute adsorption isotherm of both toluene and ethylbenzene is the liquid-solid extended multilayer BET isotherm. Despite a significant difference between the monolayer capacities of toluene (370 g/l) and ethylbenzene (170 g/l), the experimental adsorption data fit very well to single-component isotherms exhibiting the same capacities (200 g/l). The new competitive model was used for the modeling of the elution band profiles of mixtures of the two compounds. Excellent agreement between experimental and calculated profiles was observed, suggesting that the behavior of the toluene-ethylbenzene adsorbed phase on the stationary phase is close to ideal. For example, the concentrations measured for the intermediate plateau obtained in frontal analysis differ by less than 2% from those predicted by the IAS model.


Oestrogen synthesis by the foetal rat testis in organ culture.
Testes from 19- to 21-day old rat foetuses were bisected and cultured in the presence of tritiated testosterone, androstenedione or dehydroepiandrosterone as precursors for oestrogen biosynthesis. Oestrone and oestradiol formed were identified by recrystallization to constant specific activity, and their conversion rate was determined after isotopic dilution. Both oestrogens formed from either precursor, their conversion rate being about 0.05% for oestradiol and 0.015% for oestrone.


The role of soluble E-selectin in HIV associated preeclampsia.
To determine the serum concentration of soluble E-selectin (sE-selectin) in HIV associated preeclampsia. The study population (n = 72) consisted of normotensive pregnant (n = 36) and preeclamptic (n = 36) women stratified by HIV status (negative vs. positive). Serum concentrations of sE-selectin were quantified using the MilliPlex multiplex immunoassay method. Statistical analyses were conducted using GraphPad Prism software. When stratified by pregnancy type and HIV status, serum sE-selectin levels were elevated in the preeclamptic HIV-negative group compared to the normotensive HIV-negative group (p = 0.0070**). Gestational age, systolic blood pressure, diastolic blood pressure and baby weight were statistically different across the study groups (p < 0.0001). This study demonstrates an elevation of sE-selectin in preeclamptic HIV-negative compared to the normotensive HIV-negative group. However, when stratified by HIV status, there was no significant difference observed in preeclamptic HIV-positive and normotensive HIV-positive groups. The findings of this small-scale study suggest that sE-selectin may be used as a biomarker or an early identifier of preeclampsia. Studies with large numbers should be considered to confirm our findings.


Multivariate analysis of factors associated with renal dysfunction in patients with obstructive jaundice.
The aim was to evaluate the factors determining preoperative renal dysfunction in patients with obstructive jaundice. In a prospective cross-sectional observational study, 63 patients, 27 with benign and 36 with malignant obstructive jaundice, were investigated at admission and compared with 25 healthy control subjects. Variables analysed included extracellular body water (ECW) compartment, plasma levels of aldosterone, renin, atrial natriuretic peptide, vasopressin, nitric oxide, endothelin (ET) 1 and prostaglandin E2 (PGE2), urinary nitric oxide and PGE2, serum albumin and renal function. The metabolic profile of obstructive jaundice was characterized by a depletion of the ECW (P = 0.004), and increased plasma levels of atrial natriuretic peptide (P < 0.001), ET-1 (P = 0.044), vasopressin (P = 0.017), aldosterone (P = 0.005) and renin (P = 0.001). Increased plasma (P < 0.001) and urinary (P = 0.001) PGE2 levels were also found. Fifty-four per cent of patients had a creatinine clearance of less than 70 ml/min. In multivariate analysis, serum bilirubin, renin, ET-1, PGE2, decreased urinary sodium excretion and age were identified as predictors of renal dysfunction. Renal dysfunction in patients with obstructive jaundice was associated with the degree of biliary obstruction, age of the patient and reduced urinary sodium excretion. These alterations were closely related to derangements in sodium- and water-regulating hormones.


Subcortical leukomalacia. Relationship to development of the cerebral sulcus and its vascular supply.
The development of the microvascular architecture of the cerebral cortex and white matter was studied in the preterm, term, and older infant, using postmortem cerebral angiography and metal impregnation studies. During the first few months after birth, a relatively avascular triangle forms in the white matter at the depth of the sulcus. Subcortical leukomalacia occurs in this triangle as well as in border zones between the major cerebral arteries.


Equestrian perniosis: A case report and review of the literature.
Equestrian perniosis is a rare form of perniosis that is predominantly seen in young female equestrians who ride in cold temperatures. Tight fitting clothing, age under 35 years, and smoking can contribute to the disease manifestation. The diagnosis can be determined from a thorough history and physical examination. However, a biopsy can be taken to confirm the diagnosis. Although many cases are self-limiting and resolve within a few days to weeks of diagnosis, nifedipinie can be considered as a therapeutic measure for persistent cases. Measures such as wearing loose fitting clothing and horseback riding in warmer temperatures and for shorter time periods can prevent recurrence.


In vitro chemosensitivity testing of leukemic cells: development of a semiautomated colorimetric assay.
A rapid chemosensitivity assay was developed, employing the human continuous leukemic cell lines HL 60, K 562, FLG 29.1. This automated colorimetric assay is based on the characteristic of viable, metabolically active cells to cleave p-iodonitrotetrazolium violet (INT) into a red formazan derivative, whose optical density is readable at 492 nm by an automated microtiter-plate reader photometer. A linear relationship was found between the viable cell number and the optical density of INT cleaved by the cellular samples. Dead cells did not reduce INT and did not interfere with the formazan derivative generation and the photometric reading. Leukemic cell lines were also tested for INT formazan derivative generation after exposure to antileukemic drugs at various concentrations, representative of plasma levels obtainable in vivo. A dose-dependent inhibition was detected, with different sensitivity patterns, related both to the drugs and to the different cell lines. A significant correlation between the viable cell number and the amount of tetrazolium salt cleaved was also demonstrated after drug exposure. INT assay allows the processing of a great number of samples and gives the opportunity to screen several drugs, saving time and yielding fully reliable results.


Regional cerebral blood flow: estimation by means of nonmetabolized diffusible tracers--an overview.
Visualization and measurement of functional activity throughout the human brain has been made possible by position emission tomography (PET) using tracers, the accumulation of which in the various regions of the brain are functions of regional blood flow or energy metabolism. Certain principles and mathematical expressions describing the exchange of diffusible, nonmetabolized substances between capillary and brain, published nearly 40 years ago, have been useful in this development.


Interactions with alloparents are associated with the diversity of infant skin and fecal bacterial communities in Chicago, United States.
Social interactions shape the infant microbiome by providing opportunities for caregivers to spread bacteria through physical contact. With most research focused on the impact of maternal-infant contact on the infant gut microbiome, it is unclear how alloparents (i.e., caregivers other than the parents) influence the bacterial communities of infant body sites that are frequently contacted during bouts of caregiving, including the skin. To begin to understand how allocare may influence the diversity of the infant microbiome, detailed questionnaire data on infant-alloparent relationships and specific allocare behaviors were coupled with skin and fecal microbiome samples (four body sites) from 48 infants living in Chicago, United States. Data from 16S rRNA gene amplicon sequencing indicated that infant skin and fecal bacterial diversity showed strong associations (positive and negative) to having female adult alloparents. Alloparental feeding and co-sleeping displayed stronger associations to infant bacterial diversity compared to playing or holding. The associations with allocare behaviors differed in magnitude and direction across infant body sites. Bacterial relative abundances varied by infant-alloparent relationship and breastfeeding status. This study provides some of the first evidence of an association between allocare and infant skin and fecal bacterial diversity. The results suggest that infants' exposure to bacteria from the social environment may vary based on infant-alloparent relationships and allocare behaviors. Since the microbiome influences immune system development, variation in allocare that impacts the diversity of infant bacterial communities may be an underexplored dimension of the social determinants of health in early life.


A survey for antibodies against Fasciola hepatica in cattle and sheep in finland indicates a low level of exposure.
Fasciolosis is a parasitic infection caused by the liver fluke Fasciola hepatica that can have a major economic impact on livestock industry. The prevalence of the disease has recently been increasing in many North European countries. The objective of this study was to determine the prevalence of antibody against F. hepatica in Finnish cattle herds and sheep flocks during 2019 by using a commercial enzyme-linked immunosorbent assay (ELISA). Randomly selected bulk tank milk samples were obtained from 660 dairy herds. Blood samples were collected at slaughterhouses from 1944 suckler cows from 309 herds and from 1120 sheep from 95 flocks. Antibodies against F. hepatica were found in 0.45% (95% confidence interval (CI): 0.15-1.33) of the dairy herds and 0.97% (95% CI: 0.33-2.82) of the suckler cow herds. The seropositive herds were located in eastern and central Finland. None of the sampled sheep flocks tested had antibodies against F. hepatica (95% CI: 0-3.89). The results of the assays were compared with meat inspection data received from the slaughterhouses. All positive herds also had liver condemnations due to F. hepatica based on the meat inspection reports. Compared to other North European countries, the prevalence of fasciolosis in Finland can be considered low, and according to meat inspection reports, there are no indications of the prevalence increasing in Finland.


Bacterial Community of the Digestive Tract of the European Medicinal Leech (Hirudo verbana) from the Danube River.
The digestive tract of medicinal leeches from commercial suppliers has been investigated previously and comprises of a relatively simple bacterial community. However, the microbiome of medicinal leeches collected directly from the natural habitat has not been examined. In this study, we characterized the bacterial community in the digestive tract (anterior crop, posterior crop, and intestine) of the European medicinal leech, Hirudo verbana, collected from the Danube river using culture-independent and culture-dependent approaches. Culture-independent approach confirmed that the digestive tract of H. verbana carries a relatively simple bacterial community with species richness in the individual samples ranging from 43 to164. The dominant bacterial taxon was Mucinivorans sp. (49.7% of total reads), followed by Aeromonas sp. (18.7% of total reads). Several low abundance taxa, new for H. verbana, such as Phreatobacter, Taibaiella, Fluviicola, Aquabacterium, Burkholderia, Hydrogenophaga, Wolinella, and unidentified Chitinophagia, were also detected. The aerobic culturing approach showed Aeromonas veronii (Proteobacteria), the known leech symbiont, as the most dominant taxon followed by several Pseudomonas and Acidovorax spp. No significant differences in the bacterial community composition were detected among different parts of the digestive tract of individual leeches. However, the overall composition of the bacterial community among individual specimen varied significantly and this is possibly due to differences in leech age, feeding status, and blood source. Our results showed that the core bacterial community of H. verbana collected from the natural habitat is similar to that reported from the digestive tract of commercially supplied leeches maintained in the laboratory.


"Selective" serotonin 5-HT2A receptor antagonists.
Blockade of the serotonin 5-HT2A G protein-coupled receptor (5-HT2AR) is a fundamental pharmacological characteristic of numerous antipsychotic medications, which are FDA-approved to treat schizophrenia, bipolar disorder, and as adjunctive therapies in major depressive disorder. Meanwhile, activation of the 5-HT2AR by serotonergic psychedelics may be useful in treating neuropsychiatric indications, including major depressive and substance use disorders. Serotonergic psychedelics and other 5-HT2AR agonists, however, often bind other receptors, and standard 5-HT2AR antagonists lack sufficient selectivity to make well-founded mechanistic conclusions about the 5-HT2AR-dependent effects of these compounds and the general neurobiological function of 5-HT2ARs. This review discusses the limitations and strengths of currently available "selective" 5-HT2AR antagonists, the molecular determinants of antagonist selectivity at 5-HT2ARs, and the utility of molecular pharmacology and computational methods in guiding the discovery of novel unambiguously selective 5-HT2AR antagonists.


Training Programs Designed for Muscle Hypertrophy in Bodybuilders: A Narrative Review.
Bodybuilding is a sport that requires adequate training strategies in order to maximize skeletal muscle hypertrophy. The purpose of the present review was to perform a narrative assessment of the training routines designed for muscle hypertrophy used by bodybuilders. A search was carried out in the databases Pubmed/MEDLINE, Scielo, EBSCO, LILACS, SportDiscus, Web of Science, and CINAHL with the words "Resistance training" and "hypertrophy" in bodybuilders and their variations that involve the respective outcomes. Fourteen studies were identified that investigated the long-term training routines of bodybuilders. These studies demonstrate a pattern in the training organization, whereby there is a separation of training into four distinct periods: off-season, pre-contest, peak week, and post-contest. Each period has a specific spectrum of intensity load, total training volume, and exercise type (multi- or single-joint). We conclude that bodybuilding competitors employed a higher intensity load, lower number of repetitions, and longer rest intervals in the off-season than pre-contest.


Partition of nonreplicating DNA by the par system of bacteriophage P1.
P1 plasmid encodes a cis-acting centromere analog, parS, and two Par proteins that together stabilize plasmids by partitioning them to daughter bacteria. We infected immune bacteria with bacteriophage lambda into which parS had been inserted. The presence of P1 Par proteins in the infected cells was found to delay the appearance of cells cured of the nonreplicating, extrachromosomal lambda-parS DNA. This stabilization of lambda-parS, approximated in a computer simulation, demonstrates that active partition by the P1 par system does not require the act of plasmid replication and can be studied in its absence.


Psychiatric diagnoses and medication treatment among patients presenting for paediatric weight management: associations with adiposity, aerobic fitness and cardiometabolic health.
We compared anthropometry, cardiometabolic risk and aerobic fitness among obese youth in weight management who were diagnosed with one or more psychiatric disorders (PD), with (PD+M) or without (PD-M) a prescribed psychotropic medication with those with no PD (NPD). Physical measures were evaluated at baseline, and psychiatric diagnoses and related medications were identified from medical records. Of 99 patients 64 (65%) had a diagnosed PD, and of those, 23 (36%) had a related medication (PD+M). Compared to NPD, PD-M had a higher body mass index (BMI) (P = 0.003), BMI z-score (P = 0.015), percent body fat (P = 0.005) and waist circumference (P < 0.001), after adjusting for age, but PD+M did not. Cardiometabolic risk did not differ between groups, but aerobic fitness was lower among PD-M (P = 0.001) and PD+M (P = 0.008) compared to NPD. Obese youth in weight management exhibit high rates of psychiatric diagnoses that are associated with lower fitness and higher adiposity and may impact treatment efficacy.


Endurance exercise capacity in adults with cystic fibrosis.
We have compared the maximal and endurance exercise capacities in 22 (15 male) adult cystic fibrosis (CF) patients with a resting oxygen saturation (SaO2) > or = 90%, with age and sex matched controls (CON). The maximum oxygen uptake (VO2max) and heart-rate were lower for the CF group whereas the maximum ventilation reached a higher percentage of predicted. Furthermore, for the CF group there was a relationship between the % predicted VO2max and measures of lung function, confirming a ventilatory limit to maximum exercise in patients with more severe disease and a near normal maximum exercise capacity in those with mild disease. Endurance capacity, defined as the duration of exercise at 80% of each individuals VO2max, was however similar for the two groups [CF: 22.21 (15.82) vs. CON: 24.94 (13.05) min]; despite the CF group exercising under less efficient ventilatory conditions. Endurance capacity was not related to the measurements of lung function. Of the seven CF patients desaturating at maximal exercise (SaO2 < 90%), five desaturated at a work load of 80% VO2max, whereas only one desaturated at 50% VO2max. This study confirms that with increasing severity of disease, maximal exercise capacity may be limited in adult CF patients, whereas endurance capacity (at the same relative work load) is unimpaired. Furthermore, CF patients who desaturate during a progressive maximal exercise test are likely to desaturate during constant work load exercise if the intensity is high but unlikely to do so if the intensity is low. The information from these exercise tests would be of value for prescribing individual training programmes and for evaluating the effects.


The relationship of terminals containing neuropeptide Y-like immunoreactivity to lumbar sympathetic vasoconstrictor neurones in the rabbit.
The distributions of preganglionic neurones retrogradely labelled with horseradish peroxidase and of immunohistochemically identified varicose axons reactive for neuropeptide Y (NPY-IR) in the intermediate zone of rabbit lumbar spinal segments have been compared. Neurones projecting in the caudal lumbar sympathetic chain (LSC), which are mainly vasoconstrictor, were located laterally, associated with dense accumulations of NPY-IR terminals in mid L3 to caudal L4. In all other regions of the lumbar intermediate zone, there was relatively little correlation between the location of either LSC neurones, or those projecting to the pelvic viscera, and aggregations of NPY-IR axons. Most of these axons probably arise in the C1 nucleus, but it seems possible that this nucleus innervates only some groups of lumbar vasoconstrictor neurones.


Action of commonly used disinfectants against enteroviruses.
The virucidal effect of some of the most commonly used hospital disinfectants against Coxsackie B4, Echovirus 11, Poliovirus type 1 and Rotavirus have been evaluated. It was found that 'Chloros', 'Totacide 28' and methylated spirits were completely virucidal to all the viruses under study. 'Stericol' and 'Lysol' had a limited effect while 'Hibiscrub' and 'Savlon' had no effect at all.


Expectations of Lumbar Surgery Outcomes among Opioid Users Compared with Non-Users.
Matched cohort study. To compare and describe the effect of opioid usage on the expectations of lumbar surgery outcomes among patients taking opioids and patients not taking opioids. Chronic opioid use is common among lumbar-spine surgery patients. The decision to undergo elective lumbar surgery is influenced by the expected surgery outcomes. However, the effects of opioids on patients' expectations of lumbar surgery outcomes remain to be rigorously assessed. A total of 77 opioid users grouped according to dose and duration (54 "higher users," 30 "lower users") were matched 2:1 to 154 non-opioid users based on age, sex, marital status, chiropractic care, disability, and diagnosis. All patients completed a validated 20-item Expectations Survey measuring expected improvement with regard to symptoms, function, psychological well-being, and anticipated future spine condition. "Greater expectations" was defined as a higher survey score (possible range, 0-100) based on the number of items expected and degree of improvement expected. The mean Expectations Survey scores for all opioid users and all non-users were similar (73 vs. 70, p=0.18). Scores were different, however, for lower users (79) compared with matched non-users (69, p=0.01) and compared with higher users (70, p=0.01). In multivariable analysis, "reater expectations" was independently associated with having had chiropractic care (p=0.03), being more disabled (p=0.002), and being a lower-dose opioid user (p=0.03). Compared with higher users, lower users were also more likely to expect not to need pain medications 2 years after surgery (47% vs. 83%, p=0.003). Patient expectations of lumbar surgery are associated with diverse demographic and clinical variables. A lower dose and shorter duration of opioid use were associated with expecting more items and expecting more complete improvement compared with non-users. In addition, lower opioid users had greater overall expectations compared with higher users.


Short-Range Electronic Interactions between Vanadium and Molybdenum in Bimetallic SAPO-5 Catalysts Revealed by Hyperfine Spectroscopy.
Engineering two cooperative sites into a catalyst implies the onset of synergistic effects related to the existence of short-range electronic interactions between two metal components. However, these interactions and the relative structure-property correlations are often difficult to obtain. Here we show that hyperfine spectroscopy has the potential to reveal the presence of V4+-O-Mo6+ linkages assessing the degree of spin density transfer from paramagnetic V4+ species to proximal oxo-bridged Mo6+ metal ions. The dimer species were prepared by adsorption of Mo(CO)6 in the pores of SAPO-5, followed by thermal decomposition and oxidation and subsequent grafting of anhydrous VCl4(g) followed by hydrolysis and dehydration. The metal species react with SAPO protons during the exchange process and generate new Lewis acid sites, which act as redox centers. X- and Q-band EPR and HYSCORE experiments have been employed to monitor the local environment of V4+ species obtaining direct evidence for spin delocalization over 27Al, 31P, 95Mo, and 97Mo nuclei, demonstrating the presence of bimetallic V-O-Mo well-defined structures.


Catalytic mechanism and novel receptor binding sites of human parainfluenza virus type 3 hemagglutinin-neuraminidase (hPIV3 HN).
The human parainfluenza virus type 3 (hPIV3) hemagglutinin-neuraminidase (HN) has opposing functions of binding sialic acid receptors and cleaving them, facilitating virus release. The crystal structure of hPIV3 HN complexed with the substrate analogue difluorosialic acid (DFSA) revealed that catalysis by HN involves the formation of a covalently linked sialosyl-enzyme intermediate which was trapped along with a transition-state analogue resembling an oxocarbenium ion. This mechanism of enzyme catalysis was also confirmed in the crystal structure of the influenza N9 neuraminidase complexed with DFSA. Additionally, novel secondary receptor binding sites were identified in the hPIV3 HN-DFSA complex including one near the catalytic cavity which upon binding DFSA imposes subtle changes and may help the HN balance the opposing functions. Multiple receptor binding sites may increase avidity to facilitate cell binding and fusion promotion. The secondary receptor binding sites in the paramyxoviruses are so far unique to each virus type.


Novel Ultrasound Joint Selection Methods Using a Reduced Joint Number Demonstrate Inflammatory Improvement when Compared to Existing Methods and Disease Activity Score at 28 Joints.
A pilot study testing novel ultrasound (US) joint-selection methods in rheumatoid arthritis. Responsiveness of novel [individualized US (IUS) and individualized composite US (ICUS)] methods were compared with existing US methods and the Disease Activity Score at 28 joints (DAS28) for 12 patients followed for 3 months. IUS selected up to 7 and 12 most ultrasonographically inflamed joints, while ICUS additionally incorporated clinically symptomatic joints. The existing, IUS, and ICUS methods' standardized response means were -0.39, -1.08, and -1.11, respectively, for 7 joints; -0.49, -1.00, and -1.16, respectively, for 12 joints; and -0.94 for DAS28. Novel methods effectively demonstrate inflammatory improvement when compared with existing methods and DAS28.


Postulated mode of action of metals on purified human ALA-dehydratase (EC 4-2-1-24).
The effects of twelve metals at various concentrations ranging from 10(-41 to 10(-7) M have been studied on delta-aminolaevulinic acid dehydratase 9000 fold (ALA-D), isolated and purified from human red cells. The results obtained are in very good agreement with those of many authors: zinc, a constitutive element of the enzyme, behaves as an activator at low concentration, and an inhibitor at higher concentrations. The same effect is noted with aluminium, cadmium, mercury and tin. The manganese has a poor inhibitory action, copper and lead are powerful inhibitors of the enzyme. The other metals studies have no noticiable effect on ALA-D. These results agree with the following hypothesis: according to their structure, metals would bind the enzyme in one or several allosteric sites, and induce an allosteric transposition to the active or inactive form of enzyme.


The influence of pulmonary metastasectomy on survival in osteosarcoma and soft-tissue sarcomas: a retrospective analysis of survival outcomes, hospitalizations and requirements of home oxygen therapy.
Pulmonary metastasectomy for sarcoma is a widely accepted practice. Nevertheless, no previous studies has been reported the outcomes following metastasectomy compared with chemotherapy for patients with resectable and isolated pulmonary metastases. Our aim is to compare these modalities for the subset of patients with resectable metastases. Furthermore, the outcomes for patients with unresectable lung metastases are reported. Sarcoma patients with isolated lung metastases were identified and their computed axial tomography scans were reviewed by a thoracic surgeons' committee. Patients were divided into three groups: A: patients with resectable metastases treated with metastasectomy (n=29), B: patients with resectable metastases who received systemic therapy (n=17) and C: patients with unresectable metastases (n=25). Survival outcomes were plotted and compared through log-rank test for osteosarcoma and non-osteosarcoma patients. Seventy-one patients (32 with osteosarcoma and 39 with non-osteosarcoma) were eligible. Progression-free survival (PFS) was superior in patients who belonged to Group A compared with Groups B and C (8.0, 4.3 and 2.2 months, respectively, P=0.0002). Furthermore, overall survival (OS) was superior in patients who belonged to Group A compared with Groups B and C (39.6, 20.0 and 7.8 months, respectively, P<0.0001). A subanalysis for osteosarcoma patients showed superior PFS and OS for Group A vs B (median PFS 21.6 and 3.65 months, respectively, P=0.011 and median OS 34.0 and 12.4 months, respectively, P=0.0044). For non-osteosarcoma patients, there were no such significant survival differences between Groups A and B. Overall, patients who belonged to Group A had significantly lower mean percentage of their follow-up time spent admitted at hospital, and a trend towards lower requirements for home oxygen therapy. Pulmonary metastasectomy is associated with improved survival of osteosarcoma patients with resectable lung metastases. For non-osteosarcoma patients, the survival benefit of metastasectomy over chemotherapy is uncertain and warrants further evaluation. Patients with unresectable metastases have poor prognosis.


[Phenotype of immunocompetent cells and its role in antitumour immune response].
The paper contains an overview of the role of certain minor subpopulations of lymphocytes in tumour growth and of the main results obtained in the studies of the phenotype of immunocompetent cells from cancer patients. Special attention is given to selected indicators of immunity as predictors of the disease and efficacy of immunotherapy.


Positive feedback of gonadotropins in males.
The influence of estradiol and progesterone upon serum LH and FSH has been evaluated in three groups of five normal adult males. These steroids were administered to ascertain whether the hypothalamus and pituitary in the male possesses the capability for acute release and positive feedback of gonadotropins, a well established characteristic of the hypothalamus and pituitary in the female. Suppression of circulating levels of gonadotropins occurred after the oral administration of 0.1 mg of ethinyl estradiol daily for three days to experimental group 1, and after 0.1 mg ethinyl estradiol given daily for nine days plus 1.0 mg given on day 10 to experimental group 2. Positive feedback of serum LH levels occurred in two of five men of experimental group 3 after they received 0.5 mg ethinyl estradiol orally daily for three days. Three men had a rise of FSH concentration between day 5 and 8 of the administration of this drug. Ten mg of progesterone (IM) given to these men after suppression with estradiol also produced a positive feedback of FSH in three and of LH in four of the five men.


A nanomechanical strategy involving focal adhesion kinase for overcoming drug resistance in breast cancer.
Despite implementation of nanomechanical studies in cancer research, studies on the nanomechanical aspects of drug resistance in cancer are lacking. Here, we established the mechanical signatures of drug-resistant breast cancer cells using atomic force microscopy-based indentation techniques and functionalized nanopatterned substrates (NPS). Additionally, we examined the expression of proteins pertinent to focal adhesions in order to elucidate the molecular signatures responsible for the acquisition of drug resistance in breast cancer cells. Drug-resistant breast cancer cells exhibited mechanical reinforcement, increased actin stress fibers, dysfunctional mechano-reciprocal interaction with the NPS, vinculin overexpression, and improved focal adhesion kinase (FAK) activity. Owing to differences in FAK activation upon co-treatment with a FAK inhibitor, the drug-resistant breast cancer cells were eradicated more efficiently than invasive breast cancer cells having pro-survival activity. These findings demonstrated the potential of a novel co-treatment regimen using FAK inhibitors for overcoming drug resistance in breast cancer cells.


Absolute pitch judgments of familiar melodies generalize across timbre and octave.
Most listeners can determine when a familiar recording of music has been shifted in musical key by as little as one semitone (e.g., from B to C major). These findings appear to suggest that absolute pitch memory is widespread in the general population. However, the use of familiar recordings makes it unclear whether these findings genuinely reflect absolute melody-key associations for at least two reasons. First, listeners may be able to use spectral cues from the familiar instrumentation of the recordings to determine when a familiar recording has been shifted in pitch. Second, listeners may be able to rely solely on pitch height cues (e.g., relying on a feeling that an incorrect recording sounds "too high" or "too low"). Neither of these strategies would require an understanding of pitch chroma or musical key. The present experiments thus assessed whether listeners could make accurate absolute melody-key judgments when listening to novel versions of these melodies, differing from the iconic recording in timbre (Experiment 1) or timbre and octave (Experiment 2). Listeners in both experiments were able to select the correct-key version of the familiar melody at rates that were well above chance. These results fit within a growing body of research supporting the idea that most listeners, regardless of formal musical training, have robust representations of absolute pitch - based on pitch chroma - that generalize to novel listening situations. Implications for theories of auditory pitch memory are discussed.


Evaluation of screening risk and nonrisk patients for methicillin-resistant Staphylococcus aureus on admission in an acute care hospital.
Screening for methicillin-resistant Staphylocccus aureus (MRSA) is advocated as part of control measures, but screening all patients on admission to hospital may not be cost-effective. Our objective was to evaluate the additional yield of screening all patients on admission compared with only patients with risk factors and to assess cost aspects. A prospective, nonrandomized observational study of screening nonrisk patients ≤72 hours of admission compared with only screening patients with risk factors over 3 years in a tertiary referral hospital was conducted. We also assessed the costs of screening both groups. A total of 48 of 892 (5%) patients was MRSA positive; 28 of 314 (9%) during year 1, 12 of 257 (5%) during year 2, and 8 of 321 (2%) during year 3. There were significantly fewer MRSA-positive patients among nonrisk compared with MRSA-risk patients: 4 of 340 (1%) versus 44 of 552 (8%), P ≤ .0001, respectively. However, screening nonrisk patients increased the number of screening samples by 62% with a proportionate increase in the costs of screening. A backward stepwise logistic regression model identified age > 70 years, diagnosis of chronic pulmonary disease, previous MRSA infection, and admission to hospital during the previous 18 months as the most important independent predictors to discriminate between MRSA-positive and MRSA-negative patients on admission (94.3% accuracy, P < .001). Screening patients without risk factors increased the number of screenings and costs but resulted in few additional cases being detected. In a hospital where MRSA is endemic, targeted screening of at-risk patients on admission remains the most efficient strategy for the early identification of MRSA-positive patients.


Clinical, radiological profile and prognostic role of transcranial color-coded duplex in cerebral venous thrombosis: a case-control study.
Cerebral venous thrombosis is a rare type of stroke, occurring more among young individuals. The presentation is highly variable, and this can delay diagnosis and management, thereby affecting outcome. The aim is to study the clinical, radiological profile, risk factors for cerebral venous thrombosis (CVT) and the role of transcranial color-coded duplex (TCCD) in CVT prognosis among Egyptian patients. Eighty CVT patients and 80 normal healthy individuals were included. Magnetic resonance imaging, magnetic resonance venography, and genetic thrombophilia tests were done for patients. Deep cerebral venous system was evaluated using B-mode transcranial color-coded duplex (TCCD) for both groups. Showed female predominance with gender specific risk factors being the most common etiology. The most common hereditary thrombophilia was homozygous factor V Leiden mutation and anti-thrombin III (AT III). Headache was the most common presentation. Forty-three patients had transverse sinus thrombosis. Regarding TCCD, there was an increase in mean blood flow velocities, peak flow velocities and end diastolic flow velocities in deep middle cerebral vein and basal veins in CVT group compared to control group. There was a positive correlation not reaching statistical significance between flow velocities in the deep venous system and modified Rankin Scale. Clinical presentation is extremely variable. In our population, homozygous factor V Leiden mutation and AT III deficiency were the most common. Increased deep cerebral venous system flow velocities using TCCD in patients with CVT reflect their venous hemodynamic state.


Characteristic motor activity of the gastrointestinal tract in fasted conscious dogs measured by implanted force transducers.
Gastrointestinal contractile actiivity from the gastric body to the terminal ileum in conscious dogs was continuously recorded for several weeks by means of chronically implanted strain-gage force transducers. It was found that the 24-hr changes in the gastrointestinal contractile activity consisted of the two different major patterns, the digestive and interdigestive patterns. In the interdigestive state, a cyclic, recurring, caudad-moving band of strong contractions starting in the stomach and the duodenum and traversing the entire length of the small intestine was observed. When one band of strong contractions reached the distal ileum, another developed in the stomach and the duodenum again and propagated in a caudad direction. Such recycling episodes interrupted by long-lasting quiescence repeatedly occurred until the next meal. These characteristic contractile activities observed in our dogs are identical with the interdigestive myoelectric complex of the stomach and the small bowel recently reported by Code and Marlett (5). Four sequential phases (I-IV) of the migrating myoelectric complex, defined in terms of action potential activity, seem to correspond to the resting (quiescence), preceding irregular contractions, strong contractions, and subsiding contractions observed in the present study, respectively. Function and control mechanism of the interdigestive contractile activity were discussed.


Somatic embryogenesis and direct as well as indirect organogenesis in Lilium pumilum DC. Fisch., an endangered ornamental and medicinal plant.
Somatic embryogenesis and organogenesis in Lilium pumilum were successfully regulated by picloram, α-naphthaleneacetic acid (NAA), and 6-benzyladenine (BA). In organogenesis, the highest shoot regeneration frequency (92.5%) was obtained directly from bulb scales on Murashige and Skoog (MS) medium containing 2.0 mg L(-1) BA and 0.2 mg L(-1) NAA, while organogenic callus (OC) formed from leaves on MS medium supplemented with 1.0 mg L(-1) BA and 0.5 mg L(-1) NAA. Following subculture, 76.7% of OC regenerated shoots. In somatic embryogenesis, the combination of picloram and NAA increased the amount of embryogenic callus (EC) that formed with a maximum on 90.7% of all explants which formed 11 somatic embryos (SEs) per explant. Differences between EC and OC in cellular morphology and cell differentiation fate were easily observed. SEs initially formed via an exogenous or an endogenous origin. The appearance of a protoderm in heart-shaped SE and the bipolar shoot-root development in oval-shaped SE indicated true somatic embryogenesis. This protocol provides a new and detailed regulation and histological examination of regeneration pattern in L. pumilum.


Pembrolizumab as first-line treatment for advanced NSCLC in older adults: A phase II clinical trial evaluating geriatric and quality-of-life outcomes.
Since specific data on immunotherapy in older adults with advanced non-small cell lung cancer (aNSCLC) are scarce, we designed this study to determine the overall survival (OS) at one year of first-line pembrolizumab in patients older than 70 years with aNSCLC expressing PD-L1. Secondary objectives included progression-free survival, disease-specific survival, response rate, tolerability, quality of life (QoL) changes, and geriatric assessments. A single-arm, open-label, phase II clinical trial was carried out by the Spanish Lung Cancer Group between February 2018 and November 2019 at ten active sites in Spain. We included patients 70 years old and older with histological or cytological documented stage IIIB or IV aNSCLC and PD-L1 expression ≥ 1%. Each subject received 200 mg of intravenous pembrolizumab every three weeks for a maximum of two years. 83 patients were recruited for the study and 74 were finally analysed. Most were male (N = 64, 86.5%) and former smokers (N = 51, 68.9%). 24 patients (32.4%) completed at least one year of treatment, 62 (83.7%) discontinued treatment, and 30 (40.5%) experienced disease progression. The median follow-up of our cohort was 18.0 months [range: 0.1-47.7] and 46 patients (62.2%) died during the period of study. The estimated OS at one year was 61.7% (95% CI: 49.6-71.8%) and the median OS of our cohort was 19.2 months (95% CI: 11.3-25.5). QoL tended to improve throughout the study, although the differences were not statistically significant. The main geriatric scores remained stable, except for a worsening in nutritional status (P = 0.004) and an improvement in frailty (P = 0.028). Our results support treating older adults with aNSCLC expressing PD-L1 with pembrolizumab in monotherapy. The stability of most geriatric scores and the positive trend on the patients' QoL should be highlighted, although our results did not reach statistical significance.


Photophysics of anthracene-indole systems in unilamellar vesicles of DMPC and POPC: Exciplex formation and temperature effects.
The quenching of anthracene fluorescence by indole (IN), 1,2-dimethylindole (DMI), tryptophan (Trp) and indole 3-acetic acid (IAA) in dimiristoylphophatidylcholine (DMPC) and palmitoyloleoylphosphatidylcholine (POPC) lipid bilayers was investigated. The studies were carried out at 25 degrees C in POPC vesicles and below (15 degrees C) and above (35 degrees C) the phase transition temperature (24 degrees C) of DMPC. A very efficient quenching of the anthracene fluorescence by IN and DMI in the lipid membrane is observed in all cases. It is less efficient in the case of Trp and IAA. Stern-Volmer plots are linear for DMI but present a downward curvature for the other quenchers. This was interpreted as an indication of the presence of an inaccessible fraction of anthracene molecules. By a modified Stern-Volmer analysis the fraction accessible to the quenchers and the quenching constant were determined. Partition constants of the quenchers were obtained from the changes in the fluorescence emission of the indole moiety caused by the presence of the phospholipid. Using the partition constants bimolecular quenching rate constants were determined in terms of the local concentration of quencher in the lipid bilayer. These corrected rate constants are lower than those in homogeneous solvents. In the case of DMPC values the gel phase are higher than in the liquid-crystalline phase. In the quenching by IN and DMI a new, red shifted, emission band appears which could be assigned to an exciplex emission. The exciplex band is absent in the quenching by IAA and Trp.


Inhibition of influenza virus ribonucleic acid polymerase by ribavirin triphosphate.
Ribavirin 5'-triphosphate (RTP), derived from the broad-spectrum antiviral compound ribavirin (Virazole), can selectively inhibit influenza virus ribonucleic acid polymerase in a cell-free assay. Ribavirin and its 5'-monophosphate have no effect on the polymerase. The inhibition is competitive with respect to adenosine 5'-triphosphate and guanosine 5'-triphosphate. RTP also inhibits ApG- and GpC-stimulated influenza virus ribonucleic acid polymerase. Since ribavirin is phosphorylated in the cell, the inhibition of influenza multiplication in the cell may also be caused by RTP.


Spatial distribution and pollution assessment of mercury in sediments of Lake Taihu, China.
Spatial distribution patterns of total mercury (THg) in 36 surficial sediment samples representing five regions of Lake Taihu were assessed using the ArcGis geostatistical analyst module. The pollution levels of THg were also evaluated from the same five lake regions. Concentrations of THg were in a ranged of 23-168 ng/g (mean 55 ng/g) in surfical sediments, which was significantly higher than those established baseline levels of the lake. Results of THg indicated that the northern region exhibited notably higher values, the bay regions showed elevated values relative to open areas, and the lakeside regions were higher than those observed in the central area. Lake Taihu suffered moderate to high Hg pollution, and expressed clear Hg enrichment status according to monomial pollution index I(geo) and human activity factors. The concentrations of THg in the surficial sediments of Lake Taihu showed moderate-strong variation (coefficient of variation 52%). Geostatistical analysis indicated a weak spatial self-correlation, suggesting the contamination of Hg in Lake Taihu is primarily the result of anthropogenic activities.


The primary structure of the mitochondrial energy-linked nicotinamide nucleotide transhydrogenase deduced from the sequence of cDNA clones.
The amino acid sequence of the bovine mitochondrial nicotinamide nucleotide transhydrogenase, which catalyzes hydride ion transfer between NAD(H) and NADP(H) coupled to proton translocation across the mitochondrial inner membrane, has been deduced from the corresponding cDNA. Two clones were isolated by screening a bovine lambda gt10 cDNA library, using two synthetic oligonucleotides and a cDNA restriction fragment as probes. The inserts together covered 3,105 base pairs of coding sequence, corresponding to 1.035 amino acid residues. However, the reading frame at the 5' end was still open. N-terminal sequence analysis of the isolated enzyme indicated the presence of 8 additional residues. Thus, the mature transhydrogenase appeared to have 1,043 amino acid residues and a calculated molecular weight of 109,212. The deduced amino acid sequence of the transhydrogenase contained the sequences of four tryptic peptides that had been isolated from the enzyme. Two of these were the peptides that had been used for construction of the oligonucleotide probes. The other two were tryptic peptides isolated after labeling the NAD-binding site of the transhydrogenase once with [3H]p-fluorosulfonylbenzoyl-5'-adenosine (FSBA), and another time with [14C]N,N'-dicyclohexylcarbodiimide. The FSBA-labeled peptide was found to be located immediately upstream of the [14C]N,N'-dicyclohexylcarbodiimide-labeled peptide, about 230 residues from the N terminus. One of the tryptic peptides used for oligonucleotide probe construction was the same as that labeled with [3H]FSBA when the NAD-binding site was protected from FSBA attack. This peptide, which might be at the NADP-binding site of the transhydrogenase, was located very near the C terminus of the enzyme. The central region of the transhydrogenase (residues 420-850) is highly hydrophobic and appears to comprise about 14 membrane-spanning segments. By comparison, the N- and the C-terminal regions of the enzyme, which contain the NAD- and the putative NADP-binding sites, respectively, are relatively hydrophilic and are probably located outside the mitochondrial inner membrane on the matrix side. There is considerable homology between the bovine enzyme and the Escherichia coli transhydrogenase (two subunits, alpha with Mr = 54,000 and beta with Mr = 48,700), whose amino acid sequence has been determined from the genes (Clarke, D.M., Loo, T.W., Gillam, S., and Bragg, P.D. (1986) Eur. J. Biochem. 158, 647-653).


Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.
Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the "gold-standard" preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.


Validation of a multi-residue method for the determination of several antibiotic groups in honey by LC-MS/MS.
The presented multi-method was developed for the confirmation of 37 antibiotic substances from the six antibiotic groups: macrolides, lincosamides, quinolones, tetracyclines, pleuromutilines and diamino-pyrimidine derivatives. All substances were analysed simultaneously in a single analytical run with the same procedure, including an extraction with buffer, a clean-up by solid-phase extraction, and the measurement by liquid chromatography tandem mass spectrometry in ESI+ mode. The method was validated on the basis of an in-house validation concept with factorial design by combination of seven factors to check the robustness in a concentration range of 5-50 μg kg(-1). The honeys used were of different types with regard to colour and origin. The values calculated for the validation parameters-decision limit CCα (range, 7.5-12.9 μg kg(-1)), detection capability CCβ (range, 9.4-19.9 μg kg(-1)), within-laboratory reproducibility RSD(wR) (<20% except for tulathromycin with 23.5% and tylvalosin with 21.4 %), repeatability RSD(r) (<20% except for tylvalosin with 21.1%), and recovery (range, 92-106%)-were acceptable and in agreement with the criteria of Commission Decision 2002/657/EC. The validation results showed that the method was applicable for the residue analysis of antibiotics in honey to substances with and without recommended concentrations, although some changes had been tested during validation to determine the robustness of the method.


Nearly Complete Genome Sequences of Two Bovine Viral Diarrhea Virus Isolates, Subtype 1f Strain SLO/1170/2000 and Subtype 1d Strain SLO/2416/2002.
Bovine viral diarrhea virus (BVDV) subtypes 1f and 1d were isolated for the first time in Slovenia in 1999 and detected later in a majority of BVDV-infected cattle herds. Here, we report the first nearly complete genome sequences of noncytopathogenic BVDV-1f strain SLO/1170/2000 and cytopathogenic BVDV-1d strain SLO/2416/2002, isolated in Slovenia.


Time to stroke magnetic resonance imaging.
Recent guidelines on stroke neuroimaging from the American Academy of Neurology (AAN) recommend magnetic resonance imaging (MRI) over computed tomography (CT) for stroke diagnosis when patients present within 12 hours of onset. We sought to estimate the proportion of stroke MRI that is performed within 12 hours. Using the best available data, we estimated total time from symptom onset to MRI with a Monte Carlo simulation. We modeled 3 times to MRI: time to presentation, time to emergency department (ED) MRI, and time to inpatient MRI. Total time to MRI was estimated by summing these time components while varying model parameters around our base model. Sensitivity analyses assessed the relative importance of model parameters to overall MRI timing. In 2009, we estimate that 66% of stroke patients underwent MRI, 14% received an MRI in the ED, and 68% of all MRIs were obtained on hospital day 0 or 1. We estimate that 29% (95% confidence interval 24-33%) of stroke MRIs are obtained within 12 hours of onset. Sensitivity analyses revealed that even large clinical changes (eg, decreasing time to presentation) would only moderately influence this proportion. For example, if mean time to presentation were reduced to 30 minutes (from the base case estimate of 16 hours), the proportion of stroke MRI performed within 12 hours would only increase to 55.3%. Stroke guidelines favor the use of MRI over CT only during the first 12 hours from symptom onset, yet less than one-third of stroke MRIs are actually performed within this timeframe.


Interrupted reprogramming of alveolar type II cells induces progenitor-like cells that ameliorate pulmonary fibrosis.
We describe here an interrupted reprogramming strategy to generate "induced progenitor-like (iPL) cells" from alveolar epithelial type II (AEC-II) cells. A carefully defined period of transient expression of reprogramming factors (Oct4, Sox2, Klf4, and c-Myc (OSKM)) is able to rescue the limited in vitro clonogenic capacity of AEC-II cells, potentially by activation of a bipotential progenitor-like state. Importantly, our results demonstrate that interrupted reprogramming results in controlled expansion of cell numbers yet preservation of the differentiation pathway to the alveolar epithelial lineage. When transplanted to the injured lungs, AEC-II-iPL cells are retained in the lung and ameliorate bleomycin-induced pulmonary fibrosis. Interrupted reprogramming can be used as an alternative approach to produce highly specified functional therapeutic cell populations and may lead to significant advances in regenerative medicine.


Inhibition of vasoconstriction by platelet activating factor in the in situ blood perfused rat mesentery.
1. Perfusion pressure was measured in the in situ mesentery of anaesthetized rats perfused with blood at a constant 2 mL/min. 2. Increases in perfusion pressure were produced by mesenteric peri-arterial nerve stimulation at 10 Hz for 5 s at 2 min intervals and by bolus intra-arterial injections of the vasoconstrictors noradrenaline, angiotensin II and 5-hydroxytryptamine. 3. The intra-arterial infusion of platelet-activating factor (PAF) to produce a blood concentration of 3 X 10(-10) mol/L inhibited all responses to a similar extent. Intra-arterial prazosin (1-5 X 10(-9) mol/L), however, preferentially reduced responses to nerve stimulation and noradrenaline. 4. PAF at concentrations from 3 X 10(-11) to 10(-9) mol/L produced increasing inhibition of vasoconstrictor responses to nerve stimulation. The dose-response to PAF was shifted to the right by the concomitant intra-arterial infusion of the PAF antagonist SRI 63-441. 5. PAF at very low concentrations in vivo inhibits mesenteric vasoconstriction, produced by sympathetic nerve stimulation or various agonists, by a PAF-receptor mediated vasodilatation of the mesenteric vasculature.


Trichloroethylene-contaminated drinking water and congenital heart defects: a critical analysis of the literature.
The organic solvent trichloroethylene (TCE) is a metal degreasing agent and an intermediate in the production of fluorochemicals and polyvinyl chloride. TCE is also a common, persistent drinking water contaminant. Several epidemiological studies have alleged links between TCE exposure during pregnancy and offspring health problems including congenital heart defects (CHDs); however, the results of these studies are inconsistent, difficult to interpret, and involve several confounding factors. Similarly, the results of animal studies examining the potential of TCE to elicit cardiac anomalies have been inconsistent, and they have often been performed at doses far exceeding the highest levels ever reported in the drinking water. To determine what is known about the relationship between TCE and the incidence of CHDs, a comprehensive analysis of all available epidemiological data and animal studies was performed. Additionally, in vivo and in vitro studies examining possible mechanisms of action for TCE were evaluated. The specific types of heart defects alleged to have been caused by TCE in animal and human epidemiology studies were categorized by the morphogenetic process responsible for the defect in order to determine whether TCE might disrupt any specific developmental process. This analysis revealed that no single process was clearly affected by TCE, providing support that gestational TCE exposure does not increase the prevalence of CHDs. As a final evaluation, application of Hill's causality guidelines to the collective body of data revealed no indication of a causal link between gestational TCE exposure at environmentally relevant concentrations and CHDs.


Intratumoral Platelets: Harmful or Incidental Bystanders of the Tumor Microenvironment?
The tumor microenvironment (TME) has gained considerable interest because of its decisive impact on cancer progression, response to treatment, and disease recurrence. The TME can favor the proliferation, dissemination, and immune evasion of cancer cells. Likewise, there is accumulating evidence that intratumoral platelets could favor the development and aggressiveness of solid tumors, notably by influencing tumor cell phenotype and shaping the vascular and immune TME components. Yet, in contrast to other tumor-associated cell types like macrophages and fibroblasts, platelets are still often overlooked as components of the TME. This might be due, in part, to a deficit in investigating and reporting the presence of platelets in the TME and its relationships with cancer characteristics. This review summarizes available evidence from clinical and animal studies supporting the notion that tumor-associated platelets are not incidental bystanders but instead integral and active components of the TME. A particular emphasis is given to the description of intratumoral platelets, as well as to the functional consequences and possible mechanisms of intratumoral platelet accumulation.


The first successful case of ABO-incompatible living-donor lobar lung transplantation following desensitization therapy.
ABO-incompatible (ABO-I) living-donor lobar lung transplantation (LDLLT) was successfully performed in a 14-year-old girl who suffered from bronchiolitis obliterans due to graft-versus-host disease following hematopoietic stem cell transplantation. In the ABO-I LDLLT procedure, the blood type O patient received a right lower lobe donated from her blood type B father and a left lower lobe donated from her blood type O mother. Desensitization therapy, using rituximab, immunosuppressants, and plasmapheresis, was implemented for 3 weeks prior to transplantation to reduce the production of anti-B antibodies in the recipient and prevent acute antibody-mediated rejection after ABO-I LDLLT.


Performance evaluation of a depth-of-interaction detector by use of position-sensitive PMT with a super-bialkali photocathode.
Our purpose in this work was to evaluate the performance of a 4-layer depth-of-interaction (DOI) detector composed of GSO crystals by use of a position-sensitive photomultiplier tube (PMT) with a super-bialkali photocathode (SBA) by comparing it with a standard bialkali photocathode (BA) regarding the ability to identify the scintillating crystals, energy resolution, and timing resolution. The 4-layer DOI detector was composed of a 16 × 16 array of 2.9 × 2.9 × 7.5 mm(3) GSO crystals for each layer and an 8 × 8 multi-anode array type position-sensitive PMT. The DOI was achieved by a reflector control method, and the Anger method was used for calculating interacting points. The energy resolution in full width at half-maximum (FWHM) at 511 keV energy for the top layer (the farthest from the PMT) was improved and was 12.0% for the SBA compared with the energy resolution of 12.7% for the BA. As indicators of crystal identification ability, the peak-to-valley ratio and distance-to-width ratio were calculated; the latter was defined as the average of the distance between peaks per the average of the peak width. For both metrics, improvement of several percent was obtained; for example, the peak-to-valley ratio was increased from 1.78 (BA) to 1.86 (SBA), and the distance-to-width ratio was increased from 1.47 (BA) to 1.57 (SBA). The timing resolution (FWHM) in the bottom layer was improved slightly and was 2.4 ns (SBA) compared with 2.5 ns (BA). Better performance of the DOI detector is expected by use of a super bialkali photocathode.


No sex-specific effects of balance training on dynamic balance performance in healthy children.
Cross-sectional studies in children reported better balance performance for girls than for boys. Thus, balance trainability might be different between female and male children. The aim of the present study was to examine the effects of balance training (BT) on dynamic balance performance in girls compared to boys. Seventeen girls (age: 11.1 ± 0.7 years) and 22 boys (age: 11.1 ± 0.8 years) were assigned to either a BT-group or an active control (CON) group. BT was conducted over eight weeks (two sessions/week) while the CON-groups received their regular physical education lessons during the same period. Before and after treatment, dynamic balance performance was assessed by using the Lower Quarter Y-Balance (YBT-LQ) test. A series of three-way analyses of covariance (ANCOVA) were undertaken to test for within-between effects of Test [×2 (pretest vs. posttest)], Group [×2 (BT-group vs. CON-group)] and Sex [×2 (boys vs. girls)]. The three-way ANCOVA yielded a significant main effect of Test (p = 0.002-0.043, η p 2 = 0.122-0.262) and of Group (all p < 0.001, η p 2 = 0.330-0.651) but not of sex for all YBT-LQ reach directions and the composite score. Further, there were significant Test × Group interactions (all p < 0.001, η p 2 = 0.330-0.651) in favor of both BT-groups but neither Test × Sex nor Test × Group × Sex interactions were detected. We conclude that BT is an effective treatment to improve dynamic balance performance in healthy children regardless of their sex. Consequently, girls and boys can be provided with the same BT regime to enhance their postural control.


Contributions of a blended learning based on peer evaluation for teaching drug-drug interactions to undergraduate pharmacy students.
Numerous studies have pointed out the need for better training of healthcare professionals in drug-drug interactions management in order to minimize adverse drugs reactions impacts on patients. The aim of this study was to evaluate the benefits of a blended learning strategy based on peer evaluation (PE) for teaching drug-drug interactions to undergraduate pharmacy students. Third-year pharmacy students (n = 72) from the University of Limoges were involved in a hybrid teaching using the Moodle platform (2.9 version). After the theoretical lectures, an online activity was proposed to students. Each student submitted a report addressing a clinical case for peer evaluation. Students evaluated the pedagogical approach using an online survey. Quantitative benefits were assessed from students randomly assigned into two groups: PE in pharmacodynamics items (PE-PD) or PE in pharmacokinetics items (PE-PK). During this activity, three marks were given: one from peers for their evaluation work and two from teachers for oral group presentation of the clinical cases and for the final written examination. Statistics were performed using two-tailed unpaired t-test and significance was set for p < 0.05. Only a few students (n = 14, 20.6%) were aware of the peer evaluation principle and even less, only one student (n = 1, 1.5%), had already encountered it. Students considered that they benefited from this evaluation (n = 65, 95.6%); from their work being reviewed (n = 62, 91.2%) and that they participated in improving their classmates understanding (n = 59, 86.8%). Peers' allocated marks were similar in the two PE groups (PE-PD = 17.4 ± 1.4; PE-PK = 17.3 ± 1.4). Teachers' marks for oral presentation were significantly lower for pharmacodynamics than for pharmacokinetics items (PE-PD = 15.2 ± 1.2; PE-PK = 16.1 ± 2.1; p < 0.05). The final examination marks were equivalent in both groups (PE-PD = 11.0 ± 2.1; PE-PK = 11.2 ± 1.9). Besides the fact that a major short-term quantitative improvement was not detected, our teaching approach was qualified as being a positive and stimulating learning tool by students.


Preliminary validation of the short physical performance battery in older adults with multiple sclerosis: secondary data analysis.
There are relatively few standard, objective measures for studying physical function among older adults with multiple sclerosis (MS), yet such measures are necessary considering the shift in prevalence and associated consequences of both MS and older age on physical function. We undertook a preliminary examination of the construct validity of Short Physical Performance Battery (SPPB) scores in older adults with MS based on an expected differential pattern of associations with measures of lower and upper extremity function. The sample included 48 persons with MS aged 50 years and older who were enrolled in a pilot, randomized controlled trial of exercise training. Participants completed the SPPB and other objective and self-report measures of lower and upper extremity function as part of baseline testing. SPPB scores demonstrated strong associations with measures of lower extremity function (|r s| = .66-.79), and weak associations with measures of upper extremity function (|r s| = .03-.33). We provide preliminary evidence that supports the validity of scores from the SPPB as a measure of lower extremity function for inclusion in clinical research and practice involving older adults with MS.


Bis(pyridine-2-carboxyl-ato-κ2 N,O)copper(II)]-benzene-1,3,5-tri-carb-oxy-lic acid-water (1/2/2).
In the title complex, [Cu(C6H4O2N)2]·2C9H6O6·2H2O, the Cu2+ ion lies on a center of inversion and coordinates with symmetry related pyridine nitro-gen and carboxyl oxygen atoms from two pyridine-2-carb-oxy-lic acid anions, giving rise to a square-planar coordination geometry. There are weak axial bonds between Cu and an O atom of a symmetry-related trimesic acid moieties [Cu⋯O = 2.837 (2) Å] The Cu⋯O weak inter-actions and hydrogen bonds stabilize the whole structure.


Percutaneous fixation of acetabular fractures: computer-assisted determination of safe zones, angles and lengths for screw insertion.
Percutaneous retrograde screw fixation for acetabular fractures is a demanding procedure due to the complex anatomy of the pelvis and the varying narrow safe bony corridors. Limited information is available on optimal screw placement and the geometry of safe zones for screw insertion in the pelvis. Three-dimensional reconstructions of 50 consecutive CT scans of polytrauma patients (35 males, 15 females) were used to introduce three virtual CAD bolts (representing screws) into the anterior column (superior ramus of the pubic bone), posterior column (the ischial bone) and the supraacetabular region, as performed during percutaneous screw fixation. The three-dimensional (3D) position of these screws was evaluated with a computer software (MIMICS) after virtual optimal insertion. The 3D position, the narrowest zone and the distance to the hip joint of the two columns and the supraacetabular region were defined. The mean maximal screw length for the three virtual screws measured between 107.4 and 148 ± 18.7 mm. The narrowest zone of the pelvic bone (superior pubic ramus) had a width of 9.2 ± 2.4 mm. The average distances between the bolts and the hip joint were 3.9 and 19.4 ± 7.4 mm. For the anterior column (superior pubic ramus) screw, the mean lateral angle to the sagittal midline plane was 39.0 ± 3.2° and the mean posterior angle to the transversal midline plane was 15.1 ± 4.0°. The mean supraacetabular screw angles measured 22.4 ± 3.4° (medial), 35.3 ± 4.6° (cranial) and the mean angles for the ischial screw were 12.0 ± 5.4° (posterior) and 18.4 ± 4.0° (lateral). The zones for safe screw positioning are very narrow, making percutaneous screw fixation of the acetabulum a challenging procedure. The predefined angles for the most frequently positioned percutaneous screws may aid in preoperative planning, decrease operative and radiation times and help to increase safe insertion of screws.


Production cost of a real microalgae production plant and strategies to reduce it.
The cost analysis of a real facility for the production of high value microalgae biomass is presented. The facility is based on ten 3 m3 tubular photobioreactors operated in continuous mode for 2 years, data of Scenedesmus almeriensis productivity but also of nutrients and power consumption from this facility being used. The yield of the facility was close to maximum expected for the location of Almería, the annual production capacity being 3.8 t/year (90 t/ha·year) and the photosynthetic efficiency being 3.6%. The production cost was 69 €/kg. Economic analysis shows that labor and depreciation are the major factors contributing to this cost. Simplification of the technology and scale-up to a production capacity of 200 t/year allows to reduce the production cost up to 12.6 €/kg. Moreover, to reduce the microalgae production cost to approaches the energy or commodities markets it is necessary to reduce the photobioreactor cost (by simplifying its design or materials used), use waste water and flue gases, and reduce the power consumption and labor required for the production step. It can be concluded that although it has been reported that production of biofuels from microalgae is relatively close to being economically feasible, data here reported demonstrated that to achieve it by using the current production technologies, it is necessary to substantially reduce their costs and to operate them near their optimum values.


Nucleated red blood cells are a predictor of mortality in patients under extracorporeal membrane oxygenation.
The presence of Nucleated Red Blood Cells (NRBCs) in critically ill patients is associated with higher mortality and poor prognosis. Although patients on extracorporeal support such as veno-venous or veno-arterial extracorporeal membrane oxygenation (VV/VA-ECMO) are severely ill, NRBCs have rarely been investigated regarding their predictive value so far. As part of a retrospective study, we examined all cardiothoracic surgery patients from July 2019 to September 2020 who received ECMO treatment during their inpatient stay. The aim of this study was to investigate the occurrence of NRBCs during ECMO support in terms of their predictive value for mortality. In total 30 patients (age at admission: 62.7 ± 14.3 year; 26 male; ECMO duration: 8.5 ± 5.1 days; ICU duration: 18.0 ± 14.5 days) were included. 16 patients (53.3%) died during their inpatient stay. There were no significant differences in demographic characteristics between VA- or VV- ECMO patients. NRBCs occurred in all patients while under ECMO support. NRBC value was significant higher in those who died (2299.6 ± 4356.6 µl) compared to the surviving patients (133.6 ± 218.8 µl, p < 0.001). Univariate analysis found that patients with a cutoff value of ≥ 270 NRBCs/µl during ECMO support were 39 times more likely to die (OR 39.0, 95% CI 1.5-997.5, p < 0.001). 12 out of 13 patients (92.3%) with ≥ 270 NRBCs/µl died. The area under the curve (AUC) of the receiver operating characteristic curve was 0.85 (95% CI 0.69-0.96) with a sensitivity of 75.0% and a specificity of 92.9%. NRBCs appear to be an accurate biomarker for mortality in patients with ECMO support. They may be helpful in deciding if therapy becomes futile. Trial registration DRKS00023626 (December 20th 2020).


Illumina next generation sequencing data and expression microarrays data from retinoblastoma and medulloblastoma tissues.
Retinoblastoma (Rb) is a pediatric intraocular malignancy and probably the most robust clinical model on which genetic predisposition to develop cancer has been demonstrated. Since deletions in chromosome 13 have been described in this tumor, we performed next generation sequencing to test whether recurrent losses could be detected in low coverage data. We used Illumina platform for 13 tumor tissue samples: two pools of 4 retinoblastoma cases each and one pool of 5 medulloblastoma cases (raw data can be found at http://www.ebi.ac.uk/ena/data/view/PRJEB6630). We first created an in silico reference profile generated from a human sequenced genome (GRCh37p5). From this data we calculated an integrity score to get an overview of gains and losses in all chromosomes; we next analyzed each chromosome in windows of 40 kb length, calculating for each window the log2 ratio between reads from tumor pool and in silico reference. Finally we generated panoramic maps with all the windows whether lost or gained along each chromosome associated to its cytogenetic bands to facilitate interpretation. Expression microarrays was done for the same samples and a list of over and under expressed genes is presented here. For this detection a significance analysis was done and a log2 fold change was chosen as significant (raw data can be found at http://www.ncbi.nlm.nih.gov/geo/accession number GSE11488). The complete research article can be found at Cancer Genetics journal (Garcia-Chequer et al., in press) [1]. In summary here we provide an overview with visual graphics of gains and losses chromosome by chromosome in retinoblastoma and medulloblastoma, also the integrity score analysis and a list of genes with relevant expression associated. This material can be useful to researchers that may want to explore gains and losses in other malignant tumors with this approach or compare their data with retinoblastoma.


Ability of enzymes to remove Candida.
Infection by C. albicans is a significant cause of denture stomatitis. Therefore, the results of this study, which demonstrated that yeast lytic enzymes and proteolytic enzymes removed C. albicans from acrylic resin surfaces, suggest that these compounds are potentially useful denture cleansers.


Fusarium sporotrichioides Sherb. and trichothecenes associated with Fusarium-ear rot of corn before harvest.
Fusarium sporotrichioides was found to be the predominant fungus in approximately 2 % of corn ears damaged byFusarium species, before harvest during 1984 and 1985 in Poland. Concentrations of up to 1,714.9 mg/kg of total type-A trichothecenes (T-2 Toxin, HT-2 Toxin, Neosolaniol, T-2 Triol, and T-2 Tetraol) were found in hand-selected, heavily damaged kernels obtained fromF. sporotrichioides-molded ears.


Side-chain cleavage P-450 from bovine adrenocortical mitochondria. Reconstitution of enzyme activity.
The subunit structure of the cytochrome P-450 from bovine adrenocortical mitochondria responsible for the conversion of cholesterol to pregnenolone (side-chain cleavage) has been studied. Isoelectric focusing in 6 M urea reveals two fractions of identical amino acid composition which differ in apparent isoelectric points and in phospholipid content: fraction SI shows 0.6-1.8 nmol phospholipid per 53 000 daltons and pI approx. 4.0; SII shows 6.6-8.9 nmol phospholipid per 53 000 daltons and pI approx. 7.0. SII can be made to behave on isoelectric focusing like SI by removal of phospholipid and SI like SII when the extracted phospholipid is added to the protein (SI). Enzymatic activity can be restored to SII by addition of heme and to SI by addition of heme together with the phospholipid extracted from P-450 from the fractions SI and SII. This phospholipid contains at least four classes of phospholipid of which two have been tentatively identified as phosphatidylcholine and phosphatidylethanolamine. A variety of phospholipids from commercial sources do not permit reconstitution of enzyme activity. Evidence is presented to show that minor contaminants seen on polyacrylamide SDS gels are not essential for enzyme activity nor do they appear greatly to influence enzymatic activity. The possible role of phospholipid in reconstituting cytochrome P-450 activity is considered.


Molecular cloning and functional characterization of a glucose transporter (CsGLUT) in Clonorchis sinensis.
A complementary DNA (cDNA) encoding a glucose transporter of Clonorchis sinensis (CsGLUT) was isolated from the adult C. sinensis cDNA library. The open reading frame of CsGLUT cDNA consists of 1653 base pairs that encode a 550-amino acid residue protein. Hydropathy analysis suggested that CsGLUT possess 12 putative membrane-spanning domains. The Northern blot analysis result using poly(A)(+)RNA showed a strong band at ~2.1 kb for CsGLUT. When expressed in Xenopus oocytes, CsGLUT mediated the transport of radiolabeled deoxy-D-glucose in a time-dependent but sodium-independent manner. Concentration-dependency results showed saturable kinetics and followed the Michaelis-Menten equation. Nonlinear regression analyses yielded a Km value of 588.5 ± 53.0 μM and a Vmax value of 1500.0 ± 67.5 pmol/oocyte/30 min for [1,2-(3)H]2-deoxy-D-glucose. No trans-uptakes of bile acid (taurocholic acid), amino acids (tryptophan and arginine), or p-aminohippuric acid were observed. CsGLUT-mediated transport of deoxyglucose was significantly and concentration-dependently inhibited by radio-unlabeled deoxyglucose and D-glucose. 3-O-Methylglucose at 10 and 100 μM inhibited deoxyglucose uptake by ~50 % without concentration dependence. No inhibitory effects by galactose, mannose, and fructose were observed. This work may contribute to the molecular biological study of carbohydrate metabolism and new drug development of C. sinensis.


A family with hereditary angioedema and multiple immunologic disorders.
A 58-year-old man with end-stage renal disease treated with long-term ambulatory peritoneal dialysis gave a history of hereditary angioedema. Results of testing of his serum for antinuclear antibody were strongly positive, and a titer of 1:2,560 for antiribosomal antibody was documented. Three of his six children reported multiple medical problems, including episodic swelling, discoid lupus, and arthritis. An indepth study of this kindred showed a number of associated immunologic disturbances. Three children had decreased C1 esterase inhibitor and decreased C4 levels. T cell enumeration revealed low proportions of suppressor cells in these three children as well as in another unaffected child. Serum IgM level was low in the propositus, and IgG level was also decreased in one of the affected children. HLA typing failed to show a clear association of class I or class II antigens with hereditary angioedema. Family members tested did not demonstrate anti-SS-A, anti-SS-B, antinuclear antibody, anti-double-stranded DNA, anti-Sm, or anti-ribonuclear protein antibodies.


Monitoring particle aggregation processes.
A wide range of test methods for monitoring particle aggregation processes is reviewed. These include techniques for measuring aggregation rates in fundamental studies and those which are useful in the monitoring and control of practical coagulation/flocculation processes. Most emphasis is on optical methods, including light transmission (turbidity) and light scattering measurements and the fundamentals of these phenomena are briefly introduced. It is shown that in some cases, absolute aggregation rates can be derived. However, even when only relative rates can be obtained, these can still be very useful, for instance in defining optimum flocculation conditions. Some of the methods available for investigating properties of aggregates (flocs), such as size, strength and fractal dimension are also discussed, along with some related properties such as sedimentation rate and filterability of flocculated suspensions.


The nonlinearity and nonlinear convergence of CO2 emissions: Evidence from top 20 highest emitting countries.
Carbon dioxide (CO2) is the most prevalent greenhouse gas that triggers climate change, which in turn leads to catastrophic effects on trade, business, human health, and other areas. Understanding the characteristics and tendency of CO2 emissions will improve policy making and mitigation strategies. Understanding the linearity or nonlinearity and convergence or divergence of CO2 emissions is essential for selecting appropriate modeling techniques and for designing reliable policies. Therefore, this paper investigates the nonlinearity and nonlinear convergence of CO2 emissions among the world's top 20 highest emitting countries, which account for 80% of the world's total emissions. To check the nonlinearity of CO2 emissions, the McLeod-Li nonlinearity test, the Terasvirta nonlinearity test, and the Brock-Dechert-Scheinkman-LeBaron nonlinearity test are employed. The convergence or divergence of CO2 emissions is checked by using the Kilic nonlinear unit root test, the Hu and Chen nonlinear unit root test, and the Park and Shintani nonlinear unit root test. The findings revealed that the CO2 emissions process in all the 20 countries is nonlinear; 17 countries exhibit convergence in CO2 emissions while the other 3 countries diverged from 1960 to 2018. Based on the results, the nonlinear nature of CO2 emissions requires special attention from scholars when selecting estimation techniques for CO2 emissions. For countries with convergence, emissions trends can be used to forecast future values of CO2 emissions. Moreover, strong policy actions are required to achieve convergence in the countries with divergence.


Whole Genome Sequencing of the Asian Arowana (Scleropages formosus) Provides Insights into the Evolution of Ray-Finned Fishes.
The Asian arowana (Scleropages formosus) is of commercial importance, conservation concern, and is a representative of one of the oldest lineages of ray-finned fish, the Osteoglossomorpha. To add to genomic knowledge of this species and the evolution of teleosts, the genome of a Malaysian specimen of arowana was sequenced. A draft genome is presented consisting of 42,110 scaffolds with a total size of 708 Mb (2.85% gaps) representing 93.95% of core eukaryotic genes. Using a k-mer-based method, a genome size of 900 Mb was also estimated. We present an update on the phylogenomics of fishes based on a total of 27 species (23 fish species and 4 tetrapods) using 177 orthologous proteins (71,360 amino acid sites), which supports established relationships except that arowana is placed as the sister lineage to all teleost clades (Bayesian posterior probability 1.00, bootstrap replicate 93%), that evolved after the teleost genome duplication event rather than the eels (Elopomorpha). Evolutionary rates are highly heterogeneous across the tree with fishes represented by both slowly and rapidly evolving lineages. A total of 94 putative pigment genes were identified, providing the impetus for development of molecular markers associated with the spectacular colored phenotypes found within this species.


FBR murine osteosarcoma virus. II. Nucleotide sequence of the provirus reveals that the genome contains sequences acquired from two cellular genes.
The complete nucleotide sequence of the FBR proviral DNA has been determined. The provirus of 3791 nucleotides (specifying a genome of 3284 bases) encodes a single gag- fos fusion product of 554 amino acids. The fos portion of the gene lacks the sequences which code for the first 24 and the last 98 amino acids of the 380-amino acid mouse c- fos gene product. In addition, the coding region has sustained three in-frame deletions, one in the p30gag portion, and two in the fos region, as compared to the sequences of AKR-MLV and the c- fos gene, respectively. The gene product terminates in sequences, termed v-fox, that are present in uninfected mouse DNA at loci unrelated to the c- fos gene. The c-fox gene(s) is expressed as an abundant class of polyadenylated RNA in normal mouse tissues.