PLK1-mediated phosphorylation of WDR62/MCPH2 ensures proper mitotic spindle orientation.
Primary microcephaly (MCPH) is an autosomal recessive disorder characterized by congenital reduction of head circumference. Here, we identified compound heterozygous mutations c.731 C > T (p.Ser 244 Leu) and c.2413 G > T (p.Glu 805 X) in the WDR62/MCPH2 gene, which encodes the mitotic centrosomal protein WDR62, in two siblings in a Japanese family with microcephaly using whole-exome sequencing. However, the molecular and cellular pathology of microcephaly caused by WDR62/MCPH2 mutation remains unclear. To clarify the physiological role of WDR62, we used the CRISPR/Cas9 system and single-stranded oligonucleotides as a point-mutation-targeting donor to generate human cell lines with knock-in of WDR62/MCPH2 c.731 C > T (p.Ser 244 Leu) missense mutation. In normal metaphase, the mitotic spindle forms parallel to the substratum to ensure symmetric cell division, while WDR62/MCPH2-mutated cells exhibited a randomized spindle orientation caused by the impaired astral microtubule assembly. It was shown that a mitotic kinase, Polo-like kinase 1 (PLK1), is required for the maintenance of spindle orientation through astral microtubule development. In this study, we demonstrated that WDR62 is a PLK1 substrate that is phosphorylated at Ser 897, and that this phosphorylation at the spindle poles promotes astral microtubule assembly to stabilize spindle orientation. Our findings provide insights into the role of the PLK1-WDR62 pathway in the maintenance of proper spindle orientation.


Pterygium inversum unguis secondary to gel polish.
Pterygium inversum unguis (PIU) is characterized by the abnormal adherence of the hyponychium to the ventral surface of the nail plate. It can be both unsightly and painful, resulting in morbidity for patients. Gel polish is a popular nail cosmetic that has been reported to cause several complications. PIU may be another adverse outcome. To highlight a newly recognized adverse effect of a popular beauty technique. This retrospective and prospective case series reports 17 women who developed PIU after gel polish use. All study-related activities occurred at a University of Miami dermatology outpatient clinic. All 17 subjects developed PIU after two to five years of gel polish application. Nine of 17 patients reported using both UVA and LED light to cure gel polish. Of the remaining eight, five used LED light only and three did not know or could not remember. All but two patients had a resolution of PIU a few weeks after switching from gel polish to regular polish manicures. While it remains undiscerned whether PIU is related to chemicals present in the gel polish or to the application and/or removal process of such, patients and dermatologists should be aware of the potential risks of gel manicures.


A quantitative HPLC-UV method for determination of serum sorafenib and sorafenib N-oxide and its application in hepatocarcinoma patients.
Sorafenib, an oral multi-kinase inhibitor, has been approved for treatment of advanced renal-cell and hepatocellular carcinoma (HCC). However, 20% of HCC patients taking sorafenib are forced to withdraw due to adverse effects within one month after administration. Orally administered sorafenib is oxidatively metabolized, predominantly by cytochrome P450 3A4 (CYP3A4), in small-intestinal mucosa or liver. We aimed to characterize the CYP3A4-mediated metabolism of sorafenib in HCC patients and explore the contribution of the major metabolite sorafenib N-oxide to adverse effects and therapeutic efficacy. We have therefore developed a method for quantitative determination of sorafenib and its N-oxide in the present study. To optimize the preanalytical procedure, we initially ascertained the solubility of the analytes. Because they are lipophilic, solvents containing more than 40% acetonitrile were required for efficient recovery. The pretreatment procedure that we ultimately developed consists of acetonitrile precipitation, followed by extraction using octadecyl silyl-silica gel to eliminate water-soluble and hydrophilic components of serum. Application of this procedure before HPLC enabled accurate and reproducible quantitation of analytes in a linear range from 0.03 to 30 μg/mL. After characterizing the peaks in the HPLC-ultraviolet chromatogram obtained from a medicated patient by LC-tandem mass spectrometry, we applied this method to HCC patients taking sorafenib, showing large inter-individual differences in the pharmacokinetic profile. In conclusion, our assay system should be useful for follow-up of patients taking sorafenib and for exploring the association between the pharmacokinetics of sorafenib and its N-oxide and the adverse effects or therapeutic efficacy.


[Analysis of the nutritional state and body composition of school children in Granada (Spain)].
The objective of this study was to first determine the nutritional state of a sample population of school children, and then analyze the distribution pattern of their subcutaneous fat layer. The sample was composed of 977 school children from the city and province of Granada (Spain). All of the children (524 girls and 452 boys) were 9-17 years of age. To study their nutritional state and the distribution of the subcutaneous fat layer, they were given a complete anthropometric evaluation, which included measuring their weight, height, body mass index, skin folds, and body perimeters. The results obtained showed a 23.01% prevalence of overweight in the female subjects and 20.81% in the male subjects. Furthermore, the female subjects had an obesity prevalence of 12.70% in comparison to the male subjects, whose obesity prevalence was 4.98%. The distribution pattern of subcutaneous fat was found to be mainly located in the central part of body. The high percentage of overweight and obesity along with the development of a central fat distribution pattern (neck, chest, and abdomen) in these school children is clear evidence of potential cardiovascular risk.


PAM2 (piston assisted microsyringe): a new rapid prototyping technique for biofabrication of cell incorporated scaffolds.
Rapid prototyping techniques are widely used to fabricate well-defined three-dimensional structures of tissue homologs. The piston-assisted microsyringe (PAM2) is a rapid prototyping technology specifically developed for low-shear stress extrusion of viscous hydrogel solutions containing cells. In this article the working parameters of the system were established to guarantee the realization of spatially controlled hydrogel scaffolds. Moreover the shear stresses acting on the cell membrane during extrusion was investigated through a computational fluid-dynamic analysis. The computational models show that the shear stress on the cells is of the order of 100 Pa during the extrusion process. HepG2 cells encapsulated in alginate were then extruded into spatially organized hepatic lobule-like architectures and their viability and function were evaluated. The results show that the metabolic fingerprint of the cells is preserved with respect to controls and the cells are uniformly distributed through the gel scaffold.


[Motor reactions in rats during critical growth periods in the early postnatal age].
Within the first days after birth, the sleeping rats demonstrate the high rate of motor reactions (RMR) of the jerk type. With advancing age the RMR diminishes. However during a sudden change in the growth, the 25-day-old rats show an increase in the RMR of the jerk type. This is manifested by the return of the functions to the state marking the first days of life. The catecholaminergic mechanisms of the growth and development of rats are discussed.


[Cryofractographic study of the structure of yeast cells found in an anabiotic state].
Cryofractographic studies of normally growing yeast cells have shown that the length, number and arrangement of slit-like invaginations, as well as the number, frequency of arrangement and dimensions of pores on the nucleolemma, differ among various yeast species. The data on the structure of various organoids published earlier have been confirmed. The volume of all cellular organoids, with an exception of mitochondria, decreases upon dehydration. The invaginations of the plasmalemma coalesce to form a common network. This is important in the course of changes in the volume and density of the cytoplasm of cells in the anabiotic state, maintaining the structural connection of the plasmalemma with the cellular contents, which is necessary for the survival of an organism under extreme conditions.


RSK regulates activated BRAF signalling to mTORC1 and promotes melanoma growth.
The Ras/mitogen-activated protein kinase (MAPK) signalling cascade regulates various biological functions, including cell growth, proliferation and survival. As such, this pathway is often deregulated in cancer, including melanomas, which frequently harbour activating mutations in the NRAS and BRAF oncogenes. Hyperactive MAPK signalling is known to promote protein synthesis, but the mechanisms by which this occurs remain poorly understood. Here, we show that expression of oncogenic forms of Ras and Raf promotes the constitutive activation of the mammalian target of rapamycin (mTOR). Using pharmacological inhibitors and RNA interference, we find that the MAPK-activated protein kinase RSK (p90 ribosomal S6 kinase) is partly required for these effects. Using melanoma cell lines carrying activating BRAF mutations, we show that ERK/RSK signalling regulates assembly of the translation initiation complex and polysome formation, as well as the translation of growth-related messenger RNAs containing a 5'-terminal oligopyrimidine (TOP) motif. Accordingly, we find that RSK inhibition abrogates tumour growth in mice. Our findings indicate that RSK may be a valuable therapeutic target for the treatment of tumours characterized by deregulated MAPK signalling, such as melanoma.


Interference and shaping in sensorimotor adaptations with rewards.
When a perturbation is applied in a sensorimotor transformation task, subjects can adapt and maintain performance by either relying on sensory feedback, or, in the absence of such feedback, on information provided by rewards. For example, in a classical rotation task where movement endpoints must be rotated to reach a fixed target, human subjects can successfully adapt their reaching movements solely on the basis of binary rewards, although this proves much more difficult than with visual feedback. Here, we investigate such a reward-driven sensorimotor adaptation process in a minimal computational model of the task. The key assumption of the model is that synaptic plasticity is gated by the reward. We study how the learning dynamics depend on the target size, the movement variability, the rotation angle and the number of targets. We show that when the movement is perturbed for multiple targets, the adaptation process for the different targets can interfere destructively or constructively depending on the similarities between the sensory stimuli (the targets) and the overlap in their neuronal representations. Destructive interferences can result in a drastic slowdown of the adaptation. As a result of interference, the time to adapt varies non-linearly with the number of targets. Our analysis shows that these interferences are weaker if the reward varies smoothly with the subject's performance instead of being binary. We demonstrate how shaping the reward or shaping the task can accelerate the adaptation dramatically by reducing the destructive interferences. We argue that experimentally investigating the dynamics of reward-driven sensorimotor adaptation for more than one sensory stimulus can shed light on the underlying learning rules.


Simulating the spatial luminance distribution of planar light sources by sampling of ray files.
Ray files offer a very accurate description of the optical characteristics of a light source. This is essential whenever optical components are positioned in close proximity (near-field) of the light source in order to perform accurate ray tracing simulations. However, a ray file does not allow for a direct simulation of the spatial luminance distribution, i.e. luminance map, by off-the-shelf ray tracers. Simulating luminance maps of light sources or luminaires is especially important in general lighting in order to predict their general perception when viewed by the observer, and more specific, the perception of glare of luminaires having a non-uniform luminance distribution. To enable the simulation of luminance maps while maintaining the high accuracy offered by a ray file, a sampling method is presented. To validate the approach, near-field goniophotometer measurements of two planar light sources were performed. From these measurement data, ray files were extracted to which the sampling method was applied in order to obtain a set of surface sources. This approach was validated by comparing measured luminance images with simulated luminance images. A good agreement was found, validating the presented method.


[Comments on studies of industrial and non-industrial environments in Brazil: a comparative approach].
Air quality in industrial environments has been studied since the second half of the 20th century. Well-documented results show that exposure to chemical pollutants through their consumption, production, and storage can damage workers' health. New research focusing on non-industrial environments has shown unexpected correlations between air quality and health effects. Artificial ventilation systems have been related to health-related complaints and a high rate of absenteeism. Symptoms related to air quality in non-industrial environments are recognized by the World Health Organization and encompassed under the so-called sick building syndrome (SBS). In Brazil there are few studies comparing indoor air quality and health. The present study is intended to map the studies already conducted in Brazil in order to encourage further research in this area, due to its importance for public health.


[A study on the change of the primipara mother-infant interaction by infant's age in months].
The intent of this longitudinal descriptive correlational study is to investigate the change of the mother-infant interactions over the periods of one month, three months and six months of the infant's age. This study is also intended to explore the interrelationships among three major factors--the perception of pregnancy, the mother-infant interaction and the maternal attitude. The samples participated are 36 pairs of mother and infant from two university hospitals in Seoul. A data collection was made, from October in 1988 to September in 1989, for each subject at five periods of time; prenatal period (after 36 weeks in pregnancy), postpartum two or three days, one month, three months and six months of infant's age. The research tools used in this investigation are Mother-Infant Play Interaction Scale (MIPIS), Prenatal Self-Evaluation Questionnaire and Cohler's Maternal Attitude Scale. Some of the findings are as follows; 1. There is a significant increase in the mother-infant interaction from one month to three months and six months of infant's age. The highest score of the mother-infant interaction during three periods is at the time of three months. 2. The primipara's mother-infant interaction is not affected by the demographic characteristics, such as age, education and vocation of mother, types of delivery, or sex of infant. 3. Among seven categories of the perception of pregnancy, the most positively perceived categories by primiparas are acceptance of pregnancy and identification of a motherhood role; whereas the negative ones are preparation for labor, concern for well-being of self and baby, and fear of pain, helplessness and loss of control in order of negativity. 4. There is no significant relationship between the perception of pregnancy and the mother-infant interactions. 5. There is no significant change in the maternal attitude over the period of one month, three months, and six months of infant's age. 6. There is no significant relationship between the maternal attitude and the mother-infant interactions. 7. The significant relationships are found between the perception of pregnancy and maternal attitude, especially in the categories of concern for well-being of self and baby, acceptance of pregnancy, identification of a motherhood role, fear of pain, helplessness and loss of control, and relationship with husband. In conclusion, it is confirmed that primipara's mother-infant interactions change over time period, and that perception of pregnancy and the maternal attitude do not affect the mother-infant interactions despite a significant relationship between those two variables.(ABSTRACT TRUNCATED AT 400 WORDS)


Slowed lexical access is uniquely associated with positive and disorganised symptoms in schizophrenia.
This study addressed the relationship of both semantic priming and slowed lexical access to the symptoms of schizophrenia, and evaluated their association with other neurocognitive deficits. 57 outpatients with schizophrenia and 20 nonpsychiatric control subjects performed a lexical decision semantic priming task (LDT), and a brief neuropsychological battery. The schizophrenia group was also assessed with an extended Positive and Negative Symptom Scale. As expected, the schizophrenia group had significantly slower reaction times (RTs) than the control group, and poorer performance on most neuropsychological tasks. Both groups exhibited semantic priming effects in both automatic and controlled processing conditions; these effects were not significantly different between groups. RT was unrelated to age, illness duration, GAF scores, or neuroleptic dose; controlled semantic priming effects were related to illness duration only. RT to real word targets (but not to nonwords) on the LDT was significantly correlated with positive and disorganised, but not negative symptoms. The neurocognitive correlates of RT slowing were: full-scale IQ and verbal fluency, but not attention; working memory; episodic memory retrieval; executive function, or manual speed. Both controlled semantic priming effects as well as the difference between controlled and automatic priming effects were related to executive functions in general. Severity of symptoms in the three major symptom groups was generally unassociated with impairment on the neuropsychological battery. The associations of RT slowing to positive and disorganised symptoms remained even after controlling for each of the above clinical and neurocognitive measures. These findings suggest that in schizophrenia, slowed lexical access is uniquely related to positive and disorganised symptoms. This relationship is not accounted for by more general cognitive deficits, overall illness severity, or generalised effects of symptoms on cognitive function. This relationship may reflect a specific impairment in the access to semantic memory.


GOCS cohort: children's eating behavior scores and BMI.
In Chile, approximately one in three children under 6 years of age reported overweight/obese, while one in four children in elementary school suffer from obesity. There is a paucity of population-based information on the influence of childhood eating behavior on anthropometric measures related to obesity. To assess the association between eating behavior scores and Body Mass Index (BMI) z-scores in 7-10-year-old Chilean children. We conducted a cross-sectional study in 1058 children aged 7-10 (51% girls) from the 'Growth and Obesity Chilean Cohort Study' (GOCS). Direct measures of weight and height were used to compute BMI z-scores according to World Health Organization (WHO) curves. Children were classified as normal weight (-1<1 s.d.), overweight (1<2 s.d.) and obese (⩾2 s.d.). Eating behavior scores were measured through the Child Eating Behavior Questionnaire (CEBQ), previously adapted and validated for Chilean children. Multiple linear regressions were carried out using BMI z-score as the outcome and eating behavior scores as explanatory variables. All models were adjusted by age and gender. BMI z-scores were positively associated with pro-intake scores in the subscales 'enjoyment of food', 'emotional overeating' and 'food responsiveness' (P<0.0001). Contrary to other studies, 'desire for drinks' scores were also associated with BMI z-scores (P<0.0001). In contrast, food-avoidant 'satiety responsiveness', 'slowness in eating' and 'food-fussiness' scores were negatively associated with BMI z-scores (P<0.0001). We found a significant relationship between eating behavior scores and BMI z-scores in Chilean children, showing that BMI in 7-10-year-old Chilean children is positively associated with pro-intake eating behavior scores and negatively associated with anti-intake eating behavior scores. The identification of specific eating behaviors patterns related to obesity will provide important information for the implementation of prevention programs for this disease.


Lorenzo Tenchini (1852-1906): neuroanatomy and criminal anthropology.
Lorenzo Tenchini was born in Brescia and studied Medicine in Pavia where he became lecturer of Anatomy in 1880. In 1881, at the age of 29 years, he was appointed Professor of Anatomy at the University of Parma. In this city Tenchini began to study the morphology of the brains of criminals, later founding the "Museum of Criminal Anthropology". He collected brains of delinquents and their wax masks and studied the relationship between neuroanatomy and criminality. He promoted the building of a lunatic asylum in the province of Parma and was interested in social medicine, including the pellagra scourge in Northern Italy. Tenchini conducted important research work in the field of neuropsychiatry and anthropology. He was one of the founders of criminal anthropology in Italy and sought to explain criminal behavior through the study of neuroanatomy.


Identification of three single nucleotide polymorphisms in the chicken insulin-like growth factor 1 and 2 genes and their associations with growth and feeding traits.
The chicken insulin-like growth factor (IGF)1 and IGF2 genes have been partially sequenced in six individuals of each of two chicken strains of the Black Penedesenca breed (PN and MN). These two strains are genetically diverse for growth traits. Sequence alignment revealed the existence of three single nucleotide polymorphisms (SNP) (IGF1-SNP1, IGF2-SNP2, and IGF2-SNP3). These three SNP and a fourth IGF1 polymorphism (IGF1-SNP4) were typed in 60 individuals from each strain by using PCR-RFLP or primer extension analysis. No significant associations among these four SNP, growth traits, and plasma IGF1 concentration were identified. In contrast, suggestive associations (P < or = 0.05) were found between IGF1-SNP1 and average daily gain at 107 d and feed efficiency at 44, 73, and 107 d. However, these associations were not simultaneously found in both strains suggesting that they might have been produced by linkage disequilibrium with another mutation located in the IGF1 locus or another linked gene. Since the PN and MN strains differ very markedly on their feed intake, the chicken leptin gene was included in the sequence analysis. Unfortunately, attempts to amplify several regions of this gene were unsuccessful. Even when primers complementary to highly conserved regions were used, the PCR consistently failed. Other authors have reported similar problems when trying to amplify avian leptin sequences.


The role of bisphosphonates in the adjuvant setting for breast cancer.
Bone health is a critical issue in the management of women with breast cancer. Many women who develop breast cancer are postmenopausal, which already predisposes them to osteoporosis. Systemic treatments for breast cancer, including chemotherapy and endocrine therapy, decrease circulating levels of estrogen in both pre- and postmenopausal women, further accelerating the natural process of bone loss. The primary concern in breast cancer patients is that this accelerated bone loss, known as cancer treatment-induced bone loss (CTIBL), will lead to an increase in fractures, chronic pain, and loss of mobility. Bisphosphonates are highly effective at slowing the rate of bone loss in postmenopausal women with osteoporosis and at preventing skeletal-related events in women with metastatic breast cancer. Many studies are now focusing on the role of bisphosphonates in preventing CTIBL in the adjuvant setting. Both oral and intravenous bisphosphonates have shown promising activity in preventing CTIBL in patients receiving chemotherapy or hormonal therapy. In addition, emerging data indicate that the use of bisphosphonates in the adjuvant setting may prevent disease recurrence and prolong survival. Data from a number of ongoing trials will further elucidate the role of bisphosphonates in the adjuvant setting over the next few years.


Influence of Soluble Fillers in Improving Porosity of Handmade Antibiotic-Impregnated Polymethyl Methacrylate (PMMA) Beads: An in-vitro Study.
There have been many investigations on non-biodegradable materials acting as an antibiotic carrier for local drug delivery systems based on polymethyl methacrylate (PMMA) beads. However, the material is non-degradable and non-porous so that less than 5% of the encapsulated drug is released. In order to obtain better release of the antibiotics, greater porosity of the beads would be required. Adding fillers could increase the bead's porosity, thus improving the antibiotic release from the beads. The purpose of the study is to optimize release kinetics of gentamicin from handmade beads by adding fillers such as glycine and sodium chloride in different concentrations. Terms of percolation theory will qualitatively be applied in interpreting the final results. Model beads were made by blending the antibiotics (gentamicin) with powdered PMMA, prepared with the inclusion of glycine and different concentration of sodium chloride in 100% monomer. To determine the gentamicin release, beads were placed in phosphate buffered saline (PBS) and aliquots were taken at designated times to measure the gentamicin concentration. Addition of glycine yielded 16 % release of the total amount of gentamicin incorporated in 24 hours. Subsequent addition of sodium chloride resulted in an increased gentamicin release, with little or no difference in gentamicin release once 16 g or more sodium chloride was added (gentamicin release 100% of the amount incorporated). In conclusion, addition of glycine and sodium chloride resulted in an increased release of gentamicin; however, the combination without sodium chloride seemed to have an inhibitory effect on the gentamicin release.


A brief introduction to mixed effects modelling and multi-model inference in ecology.
The use of linear mixed effects models (LMMs) is increasingly common in the analysis of biological data. Whilst LMMs offer a flexible approach to modelling a broad range of data types, ecological data are often complex and require complex model structures, and the fitting and interpretation of such models is not always straightforward. The ability to achieve robust biological inference requires that practitioners know how and when to apply these tools. Here, we provide a general overview of current methods for the application of LMMs to biological data, and highlight the typical pitfalls that can be encountered in the statistical modelling process. We tackle several issues regarding methods of model selection, with particular reference to the use of information theory and multi-model inference in ecology. We offer practical solutions and direct the reader to key references that provide further technical detail for those seeking a deeper understanding. This overview should serve as a widely accessible code of best practice for applying LMMs to complex biological problems and model structures, and in doing so improve the robustness of conclusions drawn from studies investigating ecological and evolutionary questions.


Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study.
2 dimensional (2D) strain analysis detects subclinical left ventricular (LV) systolic dysfunction. Our aim was to evaluate changes in LV systolic and diastolic function in breast cancer patients early after anthracycline chemotherapy, and to identify predisposing factors. 140 patients were assessed by detailed echocardiography before and within seven days post treatment. LV ejection fraction (LVEF), global longitudinal strain (GLS), strain rate and radial and circumferential strain were assessed. Additionally, left atrial volumes and LV diastolic parameters were evaluated. LVEF although reduced after treatment, remained within the normal range (60±3% vs. 59±3%, p = 0.04). Triplane GLS was significantly reduced after treatment (-20.0±1.6% vs. -19.1±1.8%, p<0.001). Subclinical LV dysfunction (>11% reduction in GLS compared to before therapy) occurred in 22% (29/135). Impaired diastolic function grade significantly increased from 46% to 57% (p<0.001) after treatment. Furthermore, diastolic dysfunction was more common in the subgroup group with reduced systolic GLS compared to those without changes in GLS (30% vs. 11%; p = 0.04). No risk factors or clinical parameters were associated with the development of subclinical LV dysfunction; however the percentage change in early diastolic strain rate and the E velocity were independent predictors of >11% reduction in GLS. Twenty two percent of patients had subclinical LV dysfunction by GLS, whilst none had cardiotoxicity defined by LVEF, demonstrating that GLS is more sensitive for detection of subclinical LV systolic dysfunction immediately after anthracycline therapy. Diastolic dysfunction increased, particularly in the group with reduced GLS, demonstrating the close pathophysiological relationship between systolic and diastolic function.


The effects of childhood, adult, and community socioeconomic conditions on health and mortality among older adults in China.
Using a large, nationally representative longitudinal sample of Chinese aged 65 and older, this study examines the effects of childhood, adult, and community socioeconomic conditions on mortality and several major health outcomes. The role of social mobility is also tested. We find that childhood socioeconomic conditions exert long-term effects on functional limitations, cognitive impairment, self-rated health, and mortality independent of adult and community socioeconomic conditions. Achieved conditions matter for most outcomes as well, considering that adult and community socioeconomic conditions have additional impacts on health among Chinese elders. The majority of the effects of childhood conditions are not mediated by adult and community conditions. The results also show that social mobility and health in later life are linked in complex ways and that psychosocial factors have marginal explanatory power for the effects of socioeconomic conditions. Overall, this study provides new longitudinal evidence from China to support the notion that health and mortality at older ages are influenced by long-term and dynamic processes structured by the social stratification system. We discuss our findings in the context of the life course and ecological perspective, emphasizing that human development is influenced by a nexus of social experiences that impact individuals throughout life.


Structural and mechanical changes of uterine arteries during pregnancy in the pig.
A dramatic 15-fold increase in uterine blood flow in pigs occurs during pregnancy in association with marked increases in uterine arterial (UA) diameter. This study was conducted to determine UA collagen and elastin content, diameter, alpha 1- and alpha 2-adrenergic receptor (AR) numbers, norepinephrine (NE) and in vitro reactivity to phenylephrine on d 0, 20, 50, 80 and 110 of pregnancy in the pig. Uterine arterial collagen content declined progressively throughout pregnancy (P less than .01), whereas the content of elastin remained constant from d 0 to d 80, then increased (P less than .05) from d 80 to d 110. The UA collagen to elastin ratio was correlated with UA diameter (r = -.69; P less than .01), which increased from 4.5 mm on d 0 to 9.0 mm on d 110. Uterine arterial alpha 1-AR numbers remained low and constant throughout pregnancy, consistent with its retained ability to contract in response to phenylephrine. Uterine arterial NE content declined (P less than .05) from d 20 to d 80 before increasing slightly to d 110. Uterine arterial alpha 2-AR numbers remained high from d 0 to d 80 before decreasing (P less than .05) to low values on d 110. These data are consistent with a reduced adrenergic neuronal control and increased elasticity of the UA during pregnancy in the pig.


The role of interventional radiology in the management of hepatocellular carcinoma.
Hepatocellular carcinoma (hcc) is one of the most common causes of cancer-related death worldwide. Overall, liver transplantation and resection are the only available treatments with potential for cure. Various locoregional therapies are widely used to manage patients with advanced hcc or as a bridging therapy for patients with early and intermediate disease. This article reviews and evaluates the role of interventional radiology in the management of such cases by assessing various aspects of each method, such as effect on rates of survival, recurrence, tumour response, and complications. A systemic search of PubMed, medline, Ovid Medline In-Process, and the Cochrane Database of Systematic Reviews retrieved all related scientific papers for review. Needle core biopsy is a highly sensitive, specific, and accurate method for hcc grading. Portal-vein embolization provides adequate expansion of the future liver remnant, making more patients eligible for resection. In focal or multifocal unresectable early-stage disease, radiofrequency ablation tops all other thermoablative methods. However, microwave ablation is preferred in large tumours and in patients with Child-Pugh B disease. Cryoablation is preferred in recurrent disease and in patients who are poor candidates for anesthesia. Of the various transarterial modalities-transarterial chemoembolization (tace), drug-eluting beads, and transarterial radio-embolization (tare)-tace is the method of choice in Child-Pugh A disease, and tare is the method of choice in hcc cases with portal vein thrombosis. The existing data support the importance of a multidisciplinary approach in hcc management. Large randomized controlled studies are needed to provide clear indication guidelines for each method.


A reappraisal of the diagnostic and therapeutic management of uncommon histologies of primary ocular adnexal lymphoma.
Lymphoma is the most common malignancy arising in the ocular adnexa, which includes conjunctiva, lachrymal gland, lachrymal sac, eyelids, orbit soft tissue, and extraocular muscles. Ocular adnexal lymphoma (OAL) accounts for 1%-2% of non-Hodgkin lymphoma and 5%-15% of extranodal lymphoma. Histology, stage, and primary localizations are the most important variables influencing the natural history and therapeutic outcome of these malignancies. Among the various lymphoma variants that could arise in the ocular adnexa, marginal zone B-cell lymphoma (OA-MZL) is the most common one. Other types of lymphoma arise much more rarely in these anatomical sites; follicular lymphoma is the second most frequent histology, followed by diffuse large B-cell lymphoma and mantle cell lymphoma. Additional lymphoma entities, like T-cell/natural killer cell lymphomas and Burkitt lymphoma, only occasionally involve orbital structures. Because they are so rare, related literature mostly consists of anecdotal cases included within series focused on OA-MZL and sporadic case reports. This bias hampers a global approach to clinical and molecular properties of these types of lymphoma, with a low level of evidence supporting therapeutic options. This review covers the prevalence, clinical presentation, behavior, and histological and molecular features of uncommon forms of primary OAL and provides practical recommendations for therapeutic management.


The Ubiquitin-Proteasome System and F-box Proteins in Pathogenic Fungi.
The ubiquitin-proteasome system is one of the major protein turnover mechanisms that plays important roles in the regulation of a variety of cellular functions. It is composed of E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 ubiquitin ligases that transfer ubiquitin to the substrates that are subjected to degradation in the 26S proteasome. The Skp1, Cullin, F-box protein (SCF) E3 ligases are the largest E3 gene family, in which the F-box protein is the key component to determine substrate specificity. Although the SCF E3 ligase and its F-box proteins have been extensively studied in the model yeast Saccharomyces cerevisiae, only limited studies have been reported on the role of F-box proteins in other fungi. Recently, a number of studies revealed that F-box proteins are required for fungal pathogenicity. In this communication, we review the current understanding of F-box proteins in pathogenic fungi.


Chronic illness and mental health problems in pediatric practice: results from a survey of primary care providers.
The prevalence of chronic physical illnesses and their association with mental disorders was assessed using data collected by primary care pediatricians. A chronic illness was diagnosed in 1573 (15.6%) of 10,058 children aged 4 to 16 years, 945 (9.4%) of whom had a "serious" disorder, 535 (5.3%) had a minor disorder (hay fever or dermatitis), and 121 (1.2%) had a speech or language disorder. Behavioral problems were identified more often among patients with "serious" disorders than among those without chronic illnesses (2.4% vs 1.7%), as were emotional problems (5.0% vs 3.1%). Among those with "serious" conditions involving the central nervous system, the prevalence of behavioral (5.2%) and emotional (10.4%) disorders was still higher. Although children with "serious" disorders not involving the central nervous system also showed elevated prevalence rates of behavioral (2.1%) and emotional (4.5%) disturbances, this increase did not reach statistical significance. No association with "minor" chronic disorders was found. The negative impact of these mental health problems on the child was more severe when a chronic illness was also present, but referrals for mental health services did not reflect his association.


Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1.
The ubiquitous EBV causes infectious mononucleosis and is associated with several types of cancers. The EBV genome encodes an early gene product, BARF1, which contributes to pathogenesis, potentially through growth-altering and immune-modulating activities, but the mechanisms for such activities are poorly understood. We have determined the crystal structure of BARF1 in complex with human macrophage-colony stimulating factor (M-CSF), a hematopoietic cytokine with pleiotropic functions in development and immune response. BARF1 and M-CSF form a high-affinity, stable, ring-like complex in both solution and the crystal, with a BARF1 hexameric ring surrounded by three M-CSF dimers in triangular array. The binding of BARF1 to M-CSF dramatically reduces but does not completely abolish M-CSF binding and signaling through its cognate receptor FMS. A three-pronged down-regulation mechanism is proposed to explain the biological effect of BARF1 on M-CSF:FMS signaling. These prongs entail control of the circulating and effective local M-CSF concentration, perturbation of the receptor-binding surface of M-CSF, and imposition of an unfavorable global orientation of the M-CSF dimer. Each prong may reduce M-CSF:FMS signaling to a limited extent but in combination may alter M-CSF:FMS signaling dramatically. The downregulating mechanism of BARF1 underlines a viral modulation strategy, and provides a basis for understanding EBV pathogenesis.


Understanding parental stressors: an investigation of British tennis-parents.
In this study, we examined the stressors experienced by British tennis-parents. The parents (n = 123) completed an extensive survey focused on the internal and external demands that they had encountered through having a child compete in the sport. The survey consisted of open-ended questions related to competition, coaching, organizational, personal, and developmental issues. Inductive and deductive content analysis resulted in the development of seven core themes of tennis-parental stressor: competition, coaches, finance, time, siblings, organization-related, and developmental. Parents experienced a diverse number of competitive stressors indicating the particular difficulties they faced before, during, and after matches involving their child, opponents, other parents, and officials. They also reported a wide range of organizational stressors that paralleled the financial, social, and personal investments that accompanied their support roles. The results of this research reinforce the importance of parents possessing the necessary skills to cope with the psychological, developmental, and logistical demands of competitive tennis. Implications with respect to induction workshops and education for coaches and parents are presented, as well as consideration for governing bodies to enhance their communication channels and logistical support. Future research recommendations are posed to build upon the study of this domain in youth sport.


The Tat Substrate SufI Is Critical for the Ability of Yersinia pseudotuberculosis To Cause Systemic Infection.
The twin arginine translocation (Tat) system targets folded proteins across the inner membrane and is crucial for virulence in many important human-pathogenic bacteria. Tat has been shown to be required for the virulence of Yersinia pseudotuberculosis, and we recently showed that the system is critical for different virulence-related stress responses as well as for iron uptake. In this study, we wanted to address the role of the Tat substrates in in vivo virulence. Therefore, 22 genes encoding potential Tat substrates were mutated, and each mutant was evaluated in a competitive oral infection of mice. Interestingly, a ΔsufI mutant was essentially as attenuated for virulence as the Tat-deficient strain. We also verified that SufI was Tat dependent for membrane/periplasmic localization in Y. pseudotuberculosisIn vivo bioluminescent imaging of orally infected mice revealed that both the ΔsufI and ΔtatC mutants were able to colonize the cecum and Peyer's patches (PPs) and could spread to the mesenteric lymph nodes (MLNs). Importantly, at this point, neither the ΔtatC mutant nor the ΔsufI mutant was able to spread systemically, and they were gradually cleared. Immunostaining of MLNs revealed that both the ΔtatC and ΔsufI mutants were unable to spread from the initial infection foci and appeared to be contained by neutrophils, while wild-type bacteria readily spread to establish multiple foci from day 3 postinfection. Our results show that SufI alone is required for the establishment of systemic infection and is the major cause of the attenuation of the ΔtatC mutant.


Clinical analysis of cervical intraepithelial neoplasia with vaginal intraepithelial neoplasia.
The purpose of this prospective cohort study is to evaluate the importance of screening and its diagnostic accuracy compared with the pathological diagnosis of cervical intraepithelial neoplasia (CIN) with vaginal intraepithelial neoplasia (VAIN).The prospective study enrolled 419 patients (pts) and was conducted between February 1, 2015 and January 31, 2016 at Beijing Obstetrics and Gynecology Hospital, Capital Medical University.All enrolled pts underwent multipoint biopsy of cervix and vaginal wall directed by colposcopy. All samples of biopsy underwent pathological examination. Among them, 201 pts (48.0%) were diagnosed with CIN, 218 pts (52.0%) were diagnosed with cervicitis, and 51 pts (12.2%) were diagnosed with VAIN. It was found that the incidence of CIN in pts was 4 times higher than that of VAIN. In all 419 patients enrolled, 218 pts had cervicitis with 13 pts (6.0%) of VAIN. There were 201 pts of CIN with 38 pts (18.9%) of VAIN: including 53 pts of CIN3 with 12 pts (22.6%) of VAIN; 49 pts of CIN2 with 9 pts of VAIN (18.4%), and 99 pts of CIN1 with 17 pts of VAIN (17.2%). The incidence of CIN with VAIN (18.9%) was significantly higher than cervicitis with VAIN (6.0%) (χ = 16.39, P = .00). Our results showed that there was a significant consistency between cervical lesions and vaginal lesions (χ = 135.91, P = .00), which indicated that the increase of CIN grades may be related to an increase of the VAIN grades. Our results also showed the significant (p < .05) increase of CIN and VAIN with age (<40 years Kappa = 0.04; 40-50 years Kappa = 0.11; >50 years Kappa = 0.28).This study showed that cytological test can be used as a routine screening method for cervical lesions and vaginal diseases. If the cytology result shows abnormality, and pathological examination confirms that there is no obvious abnormal cervical disease, colposcopy directed vaginal multipoint biopsy should be conducted to exclude vaginal disease. All patients of CIN should routinely undergo vaginal multipoint biopsy (1/3 upper vagina), especially in patients with high-grade CIN and age older than 50 years.


Confusing untypical intestinal Behcet's disease: Skip ulcers with severe lower gastrointestinal hemorrhage.
Behcet's disease (BD) is a rare and life-long disorder characterized by inflammation of blood vessels throughout the body. BD was originally described in 1937 as a syndrome involving oral and genital ulceration in addition to ocular inflammation. Intestinal BD refers to colonic ulcerative lesions documented by objective measures in patients with BD. Many studies have shown that over 40% of BD patients have gastrointestinal complaints. Symptoms include abdominal pain, diarrhea, nausea, anorexia and abdominal distension. Although gastrointestinal symptoms are common, the demonstration of gastrointestinal ulcers is rare. This so-called intestinal BD accounts for approximately 1% of cases. There is no specific test for BD, and the diagnosis is based on clinical criteria. The manifestations of intestinal BD are similar to those of other colitis conditions such as Crohn's disease or intestinal tuberculosis, thus, it is challenging for gastroenterologists to accurately diagnose intestinal BD in patients with ileo-colonic ulcers. However, giant ulcers distributed in the esophagus and ileocecal junction with gastrointestinal hemorrhage are rare in intestinal BD. Here, we present a case of untypical intestinal BD. The patient had recurrent aphthous ulceration of the oral mucosa, and esophageal and ileo-colonic ulceration, but no typical extra-intestinal symptoms. During examination, the patient had massive acute lower gastrointestinal bleeding. The patient underwent ileostomy after an emergency right hemicolectomy and partial ileectomy, and was subsequently diagnosed with incomplete-type intestinal BD by pathology. The literature on the evaluation and management of this condition is reviewed.


A demonstrator for a low-cost, cordless, multi-carrier spread-spectrum system.
Because of the need for spectrally efficient systems for wireless communication, many research activities have been carried out in the area of spread-spectrum techniques. Multi-carrier spread-spectrum (MC-SS) is a new modulation technique with better spectral properties than direct-sequence spread-spectrum (DS-SS). In this paper, a new MC-SS system is introduced. A customized surface acoustic wave (SAW) filter has been designed as a fast analog correlator. A demonstrator testbed has been developed for the 2.4-GHz industrial, scientific, and medical (ISM) band. Experimental measurements of the intermediate frequency (IF) and baseband correlation are presented.


Gemcitabine for the treatment of non-small-cell lung cancer.
Platinum-based chemotherapy regimens have been the mainstay of treatment for non-small-cell lung cancer because they improve survival. Although there is no standard platinum-based regimen, combination regimens with newer agents (e.g., gemcitabine [Gemzar], paclitaxel [Taxol], and vinorelbine [Navelbine]) are superior to platinum alone or in combination with older agents (e.g., etoposide). Four phase III clinical studies demonstrate the favorable activity and toxicity profile of gemcitabine in combination with cisplatin (Platinol) for the treatment of patients with stage IIIB or IV non-small-cell lung cancer. These studies show overall response rates of approximately 30% to 60% with gemcitabine regimens versus overall response rates of 11% with cisplatin alone, 22% with cisplatin plus etoposide, 25% with cisplatin plus vinorelbine, and 40% with cisplatin plus mitomycin and ifosfamide (Ifex). Median survival time with gemcitabine regimens ranged from 8.1 to 9.8 months. Thrombocytopenia and anemia are the principal toxicities with gemcitabine regimens. Because of the favorable results with gemcitabine regimens, this drug is being evaluated in combination with carboplatin (Paraplatin) in newly diagnosed patients with stage IIIB or IV disease and good performance status, or as single-agent therapy in patients with poor performance status.


Functional connectivity patterns reflect individual differences in conflict adaptation.
Individuals differ in the ability to utilize previous conflict information to optimize current conflict resolution, which is termed the conflict adaptation effect. Previous studies have linked individual differences in conflict adaptation to distinct brain regions. However, the network-based neural mechanisms subserving the individual differences of the conflict adaptation effect have not been studied. The present study employed a psychophysiological interaction (PPI) analysis with a color-naming Stroop task to examine this issue. The main results were as follows: (1) the anterior cingulate cortex (ACC)-seeded PPI revealed the involvement of the salience network (SN) in conflict adaptation, while the posterior parietal cortex (PPC)-seeded PPI revealed the engagement of the central executive network (CEN). (2) Participants with high conflict adaptation effect showed higher intra-CEN connectivity and lower intra-SN connectivity; while those with low conflict adaptation effect showed higher intra-SN connectivity and lower intra-CEN connectivity. (3) The PPC-centered intra-CEN connectivity positively predicted the conflict adaptation effect; while the ACC-centered intra-SN connectivity had a negative correlation with this effect. In conclusion, our data demonstrated that conflict adaptation is likely supported by the CEN and the SN, providing a new perspective on studying individual differences in conflict adaptation on the basis of large-scale networks.


Genetic determinism of phenological traits highly affected by climate change in Prunus avium: flowering date dissected into chilling and heat requirements.
The present study investigated the genetic determinism of flowering date (FD), dissected into chilling (CR) and heat (HR) requirements. Elucidation of the genetic determinism of flowering traits is crucial to anticipate the increasing of ecological misalignment of adaptative traits with novel climate conditions in most temperate-fruit species. CR and HR were evaluated over 3 yr and FD over 5 yr in an intraspecific sweet cherry (Prunus avium) F1 progeny, and FD over 6 yr in a different F1 progeny. One quantitative trait locus (QTL) with major effect and high stability between years of evaluation was detected for CR and FD in the same region of linkage group (LG) 4. For HR, no stable QTL was detected. Candidate genes underlying the major QTL on LG4 were investigated and key genes were identified for CR and FD. Phenotypic dissection of FD and year repetitions allowed us to identify CR as the high heritable component of FD and a high genotype × environment interaction for HR. QTLs for CR reported in this study are the first described in this species. Our results provide a foundation for the identification of genes involved in CR and FD in sweet cherry which could be used to develop ideotypes adapted to future climatic conditions.


Antioxidant effects of heated garlic juice on cadmium-induced liver damage in rats as compared to ascorbic acid.
The antioxidant efficacy of heated garlic juice (HGJ) in liver was evaluated with that of ascorbic acid (AA) in rats exposed to acute dose of cadmium (4 mg kg(-1) bd. wt). The rats were either given HGJ (100 mg kg(-1) bd. wt) orally, daily for 4 weeks or AA (100 mg kg(-1) bd. wt) orally, daily for 4 weeks or both or cadmium (4 mg kg(-1) bd. wt) intraperitoneally for 3 days. Another group of rats was given cadmium (4 mg kg(-1) bd. wt) intraperitoneally for 3 days after pretreatment with either HGJ (100 mg kg(-1) bd. wt) or ascorbic acid (100 mg kg(-1) bd. wt) for 4 weeks and the liver excised. The results obtained show that AA and HGJ significantly reduced the level of liver malondialdehyde (MDA) induced by cadmium compared to control (p < 0.05) but AA tends to be more potent when compared with HGJ. The presence of either HGJ or AA also significantly reduced the levels of ROS in the presence of cadmium (Cd). The presence of either AA or HGJ pre-treatment produced significant increase in liver SOD and Catalase activities when compared with rats treated with Cd alone. There was no significant reduction in the activities of these enzymes in the presence of cadmium compared to control. Western blot shows that the expressions of Nrf2 and NQO1 in the liver were significantly increase by 3 and 1.7-fold respectively in the AA pretreated mice when compared with Cd. However no significant changes were seen in HGJ pretreated rats. The expression of HO-1 was not significantly increase in the AA pretreated rats. The results show that though both ascorbic acid and HGJ are efficient in preventing Cd-induced damage in the rat liver, ascorbic acid appeared to be a more powerful antioxidant than heated garlic juice in preventing cadmium-induced oxidative damage in liver and its action may be mediated in parts via Nrf2-keap1 pathway.


Intimate partner violence during the COVID-19 pandemic in Western and Southern European countries.
Intimate partner violence (IPV) is a significant problem with several negative health outcomes. Disasters are linked to increased IPV, but little is known about reporting of and strategies to address IPV during the COVID-19 pandemic. This review maps the IPV reporting during the pandemic and interventions to prevent and respond to IPV in 11 Western and Southern European countries. Government websites, news articles and pre-prints were searched using the terms 'domestic violence' or 'violence' in combination with 'Covid' or 'Corona'. Embase, PubMed, Scopus and Google Scholar were searched using the terms 'domestic violence' and 'partner violence' and 'interventions'. Six countries showed an increase in domestic violence reports (Austria, Belgium, France, Ireland, Spain and UK), two countries a drop (Italy and Portugal), two countries showed no change (The Netherlands and Switzerland) and one country did not provide comparative data (Germany). Common measures to address IPV were starting a campaign (nine countries), creating online support (seven), more funding for alternative accommodation (seven) and support (eight) and use of a code word (four). IPV reports or helpline calls in Western and Southern European countries in the first weeks of COVID-19 measures increased in six countries, remained the same in two countries and showed a decrease in two countries. While this review cannot ascertain the impact of the measures taken by the countries during the pandemic and beyond, this mapping provides a foundation for future research, and an opportunity to trace the efficacy of these strategies.


Phosphorylation of glutaminase by PKCε is essential for its enzymatic activity and critically contributes to tumorigenesis.
Glutamine metabolism plays an important role in cancer development and progression. Glutaminase C (GAC), the first enzyme in glutaminolysis, has emerged as an important target for cancer therapy and many studies have focused on the mechanism of enhanced GAC expression in cancer cells. However, little is known about the post-translational modification of GAC. Here, we report that phosphorylation is a crucial post-translational modification of GAC, which is responsible for the higher glutaminase activity in lung tumor tissues and cancer cells. We identify the key Ser314 phosphorylation site on GAC that is regulated by the NF-κB-PKCε axis. Blocking Ser314 phosphorylation by the S314A mutation in lung cancer cells inhibits the glutaminase activity, triggers genetic reprogramming, and alleviates tumor malignancy. Furthermore, we find that a high level of GAC phosphorylation correlates with poor survival rate of lung cancer patients. These findings highlight a previously unappreciated mechanism for activation of GAC by phosphorylation and demonstrate that targeting glutaminase activity can inhibit oncogenic transformation.


[Cellular mechanisms of smooth muscle contraction].
Myosin is an ATPase, able to form filaments with actin, thus initiating smooth muscle contraction (conversion of chemical energy into mechanical energy). Myosin activity is regulated by cytosolic calcium, via a calcium-calmodulin-MLCK-dependent phosphorylation. Extrusion of cytosolic calcium via calcium pumps (in the plasma membrane and sarcoplasmic reticulum) and via a sodium-calcium exchange allow smooth muscle cells to maintain their resting state. Constrictor agonists (hormones, neurotransmitters or drugs) act at membrane receptors inducing: (i) a fast and transient calcium mobilization from the sarcoplasmic reticulum, via phospholipase C (PLC) stimulation and inositol triphosphate (IP3) production or via a "calcium-induced calcium release" mechanism and opening of calcium channels in the sarcoplasmic reticulum and (ii) a slow and maintained mobilization of extracellular calcium, via the opening of voltage-dependent calcium channels in plasma membranes. Smooth muscle relaxation is ensured by a phosphatase which hydrolyzes phosphorylated myosin and decreases the calcium sensitivity of the contractile apparatus. Calcium signal is regulated at that level by: (i) protein kinase C, tyrosine kinase and arachidonic acid which inhibit phosphatase activity and (ii) cyclic AMP (cAMP) and cyclic GMP (cGMP) which enhance phosphatase activity. A second regulatory site is situated at the level of the non-contractile calcium compartment, which buffers signal transduction and where cGMP and/or cAMP enhance calcium extrusion mechanisms.


Carcinoid Tumors of the Gut.
BACKGROUND: Carcinoid tumors are the most frequently encountered endocrine tumors of the gastrointestinal tract. They are most often found in the appendix, although they can arise in any location of the gut. Carcinoid tumors may secrete a variety of bioactive substances, which can cause the complex of symptoms associated with the carcinoid syndrome. METHODS: The authors reviewed the pathology, clinical presentation, and management of carcinoid tumors with an emphasis on the surgical management. RESULTS: The primary treatment for a carcinoid tumor located anywhere in the gut is surgical. Those who have widely metastatic disease or who are anatomically unresectable may undergo cytoreductive surgical debulking and/or hepatic arterial embolization followed by palliation of symptoms with octreotide, the long-acting somatostatin analog. CONCLUSIONS: The prognosis for patients with carcinoid tumors that are fully resected is excellent. Those with hepatic metastases and the carcinoid syndrome have a less favorable prognosis.


Effect of NaF on rat tissue cAMP levels in vivo.
This investigation demonstrates that intraperitoneal injections of NaF (15 mg F/kg) results in hyperglycemia, inhibition of glycolysis, and an increase in tissue cAMP concentrations. Sodium fluoride significantly increases the cAMP concentration in liver, submaxillary gland, lung, heart, and kidney within 60 minutes following the injection.


Laboratory and clinical evaluation of a new synthetic absorbable suture for ophthalmic surgery.
A new synthetic absorbable suture, a copolymer of two simple hydroxy acids, glycolic acid and lactic acid, was evaluated in a laboratory and clinical study for its usefulness in ophthalmic surgery. The glycolactide was compared with chromic collagen of similar size. The 8/0 glycolactide showed 30% greater initial strength than 8/0 chromic collagen. Following implantation of the suture in rabbit corneas, the suture was removed at intervals and its rupture strength tested. At the end of 1 week the glycolactide retined over 90% of its initial rupture strength while chromic collagen had lost nearly 50% of its strength. After 10 days the strength of the glycolactide tended to fall rapidly and by day 21 the suture had negligible strength and began to absorb, completely disappearing by 7 weeks. Chromic collagen tended to remain in situ for many weeks although possessing negligible rupture strength. The 8/0 glycolactide was compared with 8/0 chromic collagen in suturing corneoscleral wounds of 45 consecutive patients undergoing routine cataract surgery. Handling qualities were judged and the eyes followed post-operatively to ascertain reaction to the sutures and time of final disappearance of the sutures from the eyes. The glycolactide showed no tendency to disappear from the wounds until after the fourth week. By the end of 9 weeks all the glycolactide sutures had disappeared. Chromic collagen, on the other hand, was more variable, some sutures disappearing as early as the third week while others remained in place essentially unchanged for more than 20 weeks. Neither glycolactide nor chromic collagen showed any tendency to excite reaction in the eyes and the incidence of complications was low.


Genome size evolution in pufferfish: an insight from BAC clone-based Diodon holocanthus genome sequencing.
Variations in genome size within and between species have been observed since the 1950 s in diverse taxonomic groups. Serving as model organisms, smooth pufferfish possess the smallest vertebrate genomes. Interestingly, spiny pufferfish from its sister family have genome twice as large as smooth pufferfish. Therefore, comparative genomic analysis between smooth pufferfish and spiny pufferfish is useful for our understanding of genome size evolution in pufferfish. Ten BAC clones of a spiny pufferfish Diodon holocanthus were randomly selected and shotgun sequenced. In total, 776 kb of non-redundant sequences without gap representing 0.1% of the D. holocanthus genome were identified, and 77 distinct genes were predicted. In the sequenced D. holocanthus genome, 364 kb is homologous with 265 kb of the Takifugu rubripes genome, and 223 kb is homologous with 148 kb of the Tetraodon nigroviridis genome. The repetitive DNA accounts for 8% of the sequenced D. holocanthus genome, which is higher than that in the T. rubripes genome (6.89%) and that in the Te. nigroviridis genome (4.66%). In the repetitive DNA, 76% is retroelements which account for 6% of the sequenced D. holocanthus genome and belong to known families of transposable elements. More than half of retroelements were distributed within genes. In the non-homologous regions, repeat element proportion in D. holocanthus genome increased to 10.6% compared with T. rubripes and increased to 9.19% compared with Te. nigroviridis. A comparison of 10 well-defined orthologous genes showed that the average intron size (566 bp) in D. holocanthus genome is significantly longer than that in the smooth pufferfish genome (435 bp). Compared with the smooth pufferfish, D. holocanthus has a low gene density and repeat elements rich genome. Genome size variation between D. holocanthus and the smooth pufferfish exhibits as length variation between homologous region and different accumulation of non-homologous sequences. The length difference of intron is consistent with the genome size variation between D. holocanthus and the smooth pufferfish. Different transposable element accumulation is responsible for genome size variation between D. holocanthus and the smooth pufferfish.


Exercise treadmill test in detecting asymptomatic coronary artery disease in type 2 diabetes mellitus.
The present study was designed to develop criteria for screening patients with type 2 diabetes mellitus (T2DM) for asymptomatic coronary artery disease (CAD). A total of 213 patients with T2DM without typical angina or chest pain were studied between 2002 and 2007. We also evaluated 53 patients with T2DM who had reported chest discomfort using an exercise treadmill test (ETT). Thirty-one of the 213 asymptomatic patients had positive ETT results. We performed coronary angiography on 23 of the 31 patients with a positive ETT and found that 11 of them had significant coronary stenosis. The main differences between the patients with significant stenosis and those with a negative ETT were age (63.1±9.4 vs. 53.7±10.1 years, P=0.008) and duration of diabetes (16.0±7.5 vs. 5.5±5.7 years, P<0.001). The positive predictive value (PPV) of the ETT was calculated to be 47.8%. The PPV of the ETT increased to 87.5% in elderly patients (≥60 years) with a long duration of diabetes (≥10 years). The latter value is similar to that of patients with T2DM who presented with chest discomfort or exertional dyspnea. The PPV of the ETT in symptomatic patients was 76.9%. In the interest of cost-effectiveness, screening for asymptomatic CAD could be limited to elderly patients with a duration of diabetes ≥10 years.


Biocrust-forming mosses mitigate the impact of aridity on soil microbial communities in drylands: observational evidence from three continents.
Recent research indicates that increased aridity linked to climate change will reduce the diversity of soil microbial communities and shift their community composition in drylands, Earth's largest biome. However, we lack both a theoretical framework and solid empirical evidence of how important biotic components from drylands, such as biocrust-forming mosses, will regulate the responses of microbial communities to expected increases in aridity with climate change. Here we report results from a cross-continental (North America, Europe and Australia) survey of 39 locations from arid to humid ecosystems, where we evaluated how biocrust-forming mosses regulate the relationship between aridity and the community composition and diversity of soil bacteria and fungi in dryland ecosystems. Increasing aridity was negatively related to the richness of fungi, and either positively or negatively related to the relative abundance of selected microbial phyla, when biocrust-forming mosses were absent. Conversely, we found an overall lack of relationship between aridity and the relative abundance and richness of microbial communities under biocrust-forming mosses. Our results suggest that biocrust-forming mosses mitigate the impact of aridity on the community composition of globally distributed microbial taxa, and the diversity of fungi. They emphasize the importance of maintaining biocrusts as a sanctuary for soil microbes in drylands.


Evaluation of gastroprotective activity of Plinia edulis (Vell.) Sobral (Myrtaceae) leaves in rats.
Plinia edulis, an arboreous species popularly known as "cambucá", is native to the Brazilian Atlantic Rain Forest. Despite its traditional uses, no reports are available on the safety of this utilization or on the relationship between the antiulcer activity of its extract and its phytochemical compounds. This paper reports on the investigation of the acute toxicity and gastroprotective effect of the aqueous ethanol extract of leaves of Plinia edulis on HCl/ethanol-induced ulcers. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to chromatographic fractionation after solvent partition. The extract did not show acute toxicity in mice treated with 5 g/kg p.o., but exhibited significant antiulcer activity in rats at doses of 100, 200, and 400mg/kg p.o., more active than the reference drug lansoprazole.The ethyl acetate fraction yielded beta-amyrin, oleanolic acid, ursolic acid, and maslinic acid, which were identified based on spectrometric analyses. Since antiulcerogenic activity is not restricted to one class of compounds in plants, the triterpenoids isolated in the extract can be associated with the observed effect.


Vaccine adjuvant ginsenoside Rg1 enhances immune responses against hepatitis B surface antigen in mice.
The adjuvant effect of ginsenoside Rg1 on immune responses against hepatitis B surface antigen (HBsAg) in mice was investigated. Female BALB/c mice were subcutaneously injected with saline or HBsAg antigen with or without Rg1 on days 7 and 21. Samples were collected 2 weeks after the boosting for the detection of anti-HBsAg immunoglobulin G (IgG) isotypes in sera and gamma interferon (IFN-γ) and interleukin-4 (IL-4) produced in splenocytes. The innate and adaptive immune responses were measured in mice immunized as described above. The results showed that ginsenoside Rg1 had adjuvant properties in stimulating IgG, splenocyte proliferation, and mRNA expression of cytokines IFN-γ and IL-4, as well as the expression of cell surface marker TLR4 in the HBsAg-immunized mice. These results indicate that Rg1 enhances both Th1 (IgG2b and IFN-γ) and Th2 (IgG1 and IL-4) responses. In addition, the TLR4 signaling pathway is involved in the adjuvant activities of ginsenoside Rg1.


A One-Layer Recurrent Neural Network for Real-Time Portfolio Optimization With Probability Criterion.
This paper presents a decision-making model described by a recurrent neural network for dynamic portfolio optimization. The portfolio-optimization problem is first converted into a constrained fractional programming problem. Since the objective function in the programming problem is not convex, the traditional optimization techniques are no longer applicable for solving this problem. Fortunately, the objective function in the fractional programming is pseudoconvex on the feasible region. It leads to a one-layer recurrent neural network modeled by means of a discontinuous dynamic system. To ensure the optimal solutions for portfolio optimization, the convergence of the proposed neural network is analyzed and proved. In fact, the neural network guarantees to get the optimal solutions for portfolio-investment advice if some mild conditions are satisfied. A numerical example with simulation results substantiates the effectiveness and illustrates the characteristics of the proposed neural network.


Organic anion transporters: discovery, pharmacology, regulation and roles in pathophysiology.
Our understanding of the mechanisms behind inter- and intra-patient variability in drug response is inadequate. Advances in the cytochrome P450 drug metabolizing enzyme field have been remarkable, but those in the drug transporter field have trailed behind. Currently, however, interest in carrier-mediated disposition of pharmacotherapeutics is on a substantial uprise. This is exemplified by the 2006 FDA guidance statement directed to the pharmaceutical industry. The guidance recommended that industry ascertain whether novel drug entities interact with transporters. This suggestion likely stems from the observation that several novel cloned transporters contribute significantly to the disposition of various approved drugs. Many drugs bear anionic functional groups, and thus interact with organic anion transporters (OATs). Collectively, these transporters are nearly ubiquitously expressed in barrier epithelia. Moreover, several reports indicate that OATs are subject to diverse forms of regulation, much like drug metabolizing enzymes and receptors. Thus, critical to furthering our understanding of patient- and condition-specific responses to pharmacotherapy is the complete characterization of OAT interactions with drugs and regulatory factors. This review provides the reader with a comprehensive account of the function and substrate profile of cloned OATs. In addition, a major focus of this review is on the regulation of OATs including the impact of transcriptional and epigenetic factors, phosphorylation, hormones and gender.


Inferring glaucoma status from prescriptions, diagnoses, and operations data: A Danish nationwide study.
To assess a new method for inferring glaucoma status using prescriptions data. The study population comprised all individuals living in Denmark in the period 1995 to 2018 and included 6,930,571 individuals. We used information from The National Prescription Registry on claimed prescriptions as the basis for our study (N = 223,592). We inferred glaucoma status using data on claimed prescriptions, in-hospital ICD-10 diagnoses, and in-hospital glaucoma surgeries. We infer glaucoma status in three ways using the prescription pattern: glaucoma inferred by (i) the use of a first claimed prescription, (ii) the use of a second claimed prescription with a gap of at least 90 days, and (iii) the use of a third claimed prescription for glaucoma medication, again with a gap of at least 90 days between prescriptions. Furthermore, we compared the results with alternative indications for glaucoma, namely in-hospital ICD-10-diagnosed glaucoma and in-hospital glaucoma surgery. We first determined that glaucoma status could be inferred from claimed prescription data and found that a single claimed prescription was highly correlated with the more restricted composite measure of glaucoma (R2 = 0.80, p <0.0001), with a kappa coefficient of 80%. Focusing on individuals with a confirmed in-hospital glaucoma diagnosis, we found a high sensitivity of 88% using anti-glaucomatous prescriptions as a surrogate marker for primary open-angle glaucoma (POAG). We then derived several descriptive insights. The prevalence of glaucoma increased during the period from 1996 to 2018, while the incidence was constant. We also found a decreasing trend in the ratio of the number of people diagnosed annually in hospitals to the number of people filling prescriptions. This indicated a relative increase in the number of patients treated or managed in the secondary sector. Finally, using data on diagnoses and claimed prescriptions, we found that the proportion of total noncompliant patients, i.e., patients who do not claim their prescription at any time in the study period (two decades) was at most 11.8%. This share is calculated on the basis of diagnosed patients who did not have surgery. The results was not sensitive to the glaucoma inference rule. Anti-glaucomatous medicine prescriptions can be used to infer glaucoma status, with useful implications for epidemiological research. The sensitivity is particularly high for primary open-angle glaucoma (POAG).


Isolation of Novel Sesquiterpeniods and Anti-neuroinflammatory Metabolites from Nardostachys jatamansi.
Nardostachys jatamansi contains various types of sesquiterpenoids that may play an important role in the potency of plant's anti-inflammatory effects, depending on their structure. In this study, five new sesquiterpenoids, namely kanshone L (1), kanshone M (2), 7-methoxydesoxo-narchinol (3), kanshone N (4), and nardosdaucanol (5), were isolated along with four known terpenoids (kanshone D (6), nardosinanone G (7), narchinol A (8), and nardoaristolone B (9)) from the rhizomes and roots of Nardostachys jatamansi. Their structures were determined by analyzing 1D and 2D NMR and MS data. Among the nine sesquiterpenoids, compounds 3, 4, and 8 were shown to possess dose-dependent inhibitory effects against lipopolysaccharide (LPS)-stimulated nitric oxide (NO) production in BV2 microglial cells. Furthermore, compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects by inhibiting the production of pro-inflammatory mediators, including prostaglandin E₂ (PGE₂), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) proteins, as well as pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-12 and tumor necrosis factor-α (TNF-α), in LPS-stimulated BV2 microglial cells. Moreover, these compounds were shown to inhibit the activation of the NF-κB signaling pathway in LPS-stimulated BV2 microglial cells by suppressing the phosphorylation of IκB-α and blocking NF-κB translocation. In conclusion, five new and four known sesquiterpenoids were isolated from Nardostachys jatamansi, and compounds 3, 4, and 8 exhibited anti-neuroinflammatory effects in LPS-stimulated BV2 microglial cells through inhibiting of NF-κB signaling pathway.


[Alimentary strategies in the neonatal period in the prevention of allergies].
The Authors report an update relative to the dietetic prevention strategies in the high allergic risk subject, as proposed from more recent literature. The babies with a familiar history of atopia are defined as population with allergic risk. The Authors examine the role of early exposure to cow's milk formulas and maternal diet during breast-feeding as risk factors for allergic symptoms in such babies. Moreover, they examine the indications for hydrolisated milk (partial and extensive) formulas and soy milk formulas use, as reported in published Meta-analysis and official statements of several Scientific Associations. They conclude that beyond the undoubted preventive role of exclusive breast-feeding in the first 4-6 month after birth, and of the extensively hydrolisated formulas, there are many concerns about the role for partially hydrolisated formulas and soy formulas. The Authors claim for multicentric methodologically correct trials in order to clear the controversies.


Influence of colostrum intake on piglet survival and immunity.
Colostrum intake from birth to 24 h after the onset of parturition (T24) was estimated for 526 piglets from 40 litters. Plasma concentrations of immunoglobulin G (IgG), lactate, glucose and cortisol were determined at T24 for six piglets per litter. Plasma IgG concentration was also assayed at weaning (28 days) on the same piglets. Rectal temperature was measured at T24 on all piglets. Mortality was recorded until weaning and comparisons were made between piglets that died before weaning and those that were still alive at weaning. The piglets that died before weaning had lower birth weight, lower colostrum intake, lower weight gain between birth and T24, and had a lower rectal temperature, higher plasma cortisol concentration and lower plasma IgG and glucose concentrations at T24 than piglets still alive at weaning. In addition, a higher proportion of piglets that died before weaning had difficulty taking their first breath after birth and were affected by splayleg. Considering all piglets, colostrum intake was positively related to rectal temperature and plasma glucose concentration and negatively related to plasma cortisol concentration at T24. Plasma IgG concentration at T24 was explained by colostrum intake, IgG concentration in the ingested colostrum, birth weight and birth rank (P<0.0001). Plasma IgG concentration at weaning was related to plasma IgG concentration at T24 (r=0.54; P<0.0001) and to colostrum intake (r=0.32; P<0.0001). Finally, body weight was explained by colostrum intake, birth weight and age until 6 weeks of age (P<0.0001). These results show that colostrum intake is the main determinant of piglet survival through provision of energy and immune protection and has potential long-term effects on piglet growth and immunity.


Validation of wearable visual feedback for retraining foot progression angle using inertial sensors and an augmented reality headset.
Gait retraining interventions using real-time biofeedback have been proposed to alter the loading across the knee joint in patients with knee osteoarthritis. Despite the demonstrated benefits of these conservative treatments, their clinical adoption is currently obstructed by the high complexity, spatial demands, and cost of optical motion capture systems. In this study we propose and evaluate a wearable visual feedback system for gait retraining of the foot progression angle (FPA). The primary components of the system are inertial measurement units, which track the human movement without spatial limitations, and an augmented reality headset used to project the visual feedback in the visual field. The adapted gait protocol contained five different target angles ranging from 15 degrees toe-out to 5 degrees toe-in. Eleven healthy participants walked on an instrumented treadmill, and the protocol was performed using both an established laboratory visual feedback driven by optical motion capture, and the proposed wearable system. The wearable system tracked FPA with an accuracy of 2.4 degrees RMS and ICC=0.94 across all target angles and subjects, when compared to an optical motion capture reference. In addition, the effectiveness of the biofeedback, reflected by the number of steps with FPA value ±2 degrees from the target, was found to be around 50% in both wearable and laboratory approaches. These findings demonstrate that retraining of the FPA using wearable inertial sensing and visual feedback is feasible with effectiveness matching closely an established laboratory method. The proposed wearable setup may reduce the complexity of gait retraining applications and facilitate their transfer to routine clinical practice.


Green Synthesis of Silver Nanoparticles Using Nisin and its Antibacterial Activity against Pseudomonas aeruginosa.
Green synthesized silver nanoparticles (AgNPs) have been used in a wide range of biological applications, including their use as antimicrobial agents. The aim of this study was to evaluate the antibacterial activity of green synthesis AgNPs using nisin against Pseudomonas aeruginosa (P. aeruginosa). In order to synthesize Ag-nisin, a 1 mg/ml nisin solution was mixed with a 1-mM silver nitrate solution and incubated. The Fourier transform infrared spectroscopy (FTIR) analysis was employed to determine the presence of various biomolecules around AgNPs. The AgNPs were morphologically observed and characterized using field emission scanning electron microscopy assessment, dynamic light scattering (DLS), and zeta potential analysis. The microdilution broth method based on CLSI principles was used for the assessment of the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of nisin on P. aeruginosa isolates. Field emission scanning electron microscope showed spherical shaped nanoparticles. DLS revealed that the average size of nanoparticles was 37.2 nm. The zeta potential of AgNPs was - 13.3 mV. FTIR findings revealed that nitrogen atoms of nisin's amine and amide groups are responsible for the capping and stability of the nanoparticles. The MIC and MBC showed that Ag/nisin nanoparticles had higher antimicrobial activity than nisin or AgNPs alone. The findings of this study show that the antibacterial activity of nisin can be increased by assembling it into the AgNP interface using a green chemical synthesis method. As a result, the technique may be used to develop an antibacterial formulation to enhance the effectiveness of nisin.


Resilience, self-esteem and self-compassion in adults with spina bifida.
Cross-sectional survey. To examine factors that may enhance and promote resilience in adults with spina bifida. Community-based disability organisations within Australia. Ninety-seven adults with a diagnosis of spina bifida (SB) completed a survey comprising of demographic questions in addition to standardised self-report measures of physical functioning (Craig Handicap Assessment and Reporting Technique), resilience (Connor-Davidson Resilience Scale, 10 item), self-esteem (Rosenberg Self-esteem Scale), self-compassion (Self-compassion Scale) and psychological distress (Depression Anxiety Stress Scales, 21 item). The majority (66%) of respondents reported moderate to high resilience. Physical disability impacted on coping, with greater CD-RISC 10 scores reported by individuals who were functionally independent in addition to those who experienced less medical co-morbidities. Significant correlations between resilience and psychological traits (self-esteem r=0.36, P<0.01; self-compassion r=0.40, P<0.01) were also noted. However, the combined contribution of these variables only accounted for 23% of the total variance in resilience scores (R(2)=0.227, F(5,94)=5.23, P<0.01). These findings extend current understanding of the concept of resilience in adults with a congenital physical disability. The suggestion is that resilience involves a complex interplay between physical determinants of health and psychological characteristics, such as self-esteem and self-compassion. It follows that cognitive behavioural strategies with a focus on self-management may, in part, contribute to the process of resilience in this group. Further large-scale and longitudinal research will help to confirm these findings.


Retrospective comparison of long-term ten-day/month rifaximin or mesalazine in prevention of relapse in acute diverticulitis.
Diverticular disease (DD) of the colon has an increasing burden on health services. The effectiveness of rifaximin for the treatment of DD, is not yet established. The aim of this study is to assess the impact of long-term treatment with rifaximin or mesalazine in a 10-day schedule for the prevention of recurrent diverticulitis. This is a retrospective study. We identified all consecutive patients with DD and previous acute diverticulitis (AD) in our outpatients' database; 124 patients, were included. The recommended therapy consisted of a ten-day/month treatment with either rifaximin (400 mg bid), or mesalazine (2.4 g/daily). Primary end point was AD recurrence. Between 2010 and 2014, 72 patients were treated with rifaximin and 52 with mesalazine. During a median follow-up of 15 months (range 1-50), we observed 21 episodes of AD among users of either rifaximin (n=7; 0.54 per 100 person-months), or mesalazine group (n=14; 1.46 per 100 person-months). Kaplan-Meier survival estimates of recurrent AD significantly differed between rifaximin and mesalazine groups (p=0.015). The multivariate Cox regression analysis showed that AD recurrence was significantly associated with therapy (rifaximin vs. mesalazine, adjusted HR 0.27; 95% CI: 0.10 to 0.72), age and gender. Long-term treatment with rifaximin in a 10-day schedule appears more effective than mesalazine in preventing recurrent AD.


Disruption of neurogenesis and cortical development in transgenic mice misexpressing Olig2, a gene in the Down syndrome critical region.
The basic helix-loop-helix (bHLH) transcription factor Olig2 is crucial for mammalian central nervous system development. Human ortholog OLIG2 is located in the Down syndrome critical region in trisomy 21. To investigate the effect of Olig2 misexpression on brain development, we generated a developmentally regulated Olig2-overexpressing transgenic line with a Cre/loxP system. The transgenic mice with Olig2 misexpression in cortical neural stem/progenitor cells exhibited microcephaly, cortical dyslamination, hippocampus malformation, and profound motor deficits. Ectopic misexpression of Olig2 impaired cortical progenitor proliferation and caused precocious cell cycle exit. Massive neuronal cell death was detected in the developing cortex of Olig2-misexpressing mice. In addition, Olig2 misexpression led to a significant downregulation of neuronal specification factors including Ngn1, Ngn2 and Pax6, and a defect in cortical neurogenesis. Chromatin-immunoprecipitation and sequencing (ChIP-Seq) analysis indicates that Olig2 directly targets the promoter and/or enhancer regions of Nfatc4, Dscr1/Rcan1 and Dyrk1a, the critical neurogenic genes that contribute to Down syndrome phenotypes, and inhibits their expression. Together, our study suggests that Olig2 misexpression in neural stem cells elicits neurogenesis defects and neuronal cell death, which may contribute to developmental disorders including Down syndrome, where OLIG2 is triplicated on chromosomal 21.


Resolution of pulmonary edema. Thirty years of progress.
In the last 30 years, we have learned much about the molecular, cellular, and physiological mechanisms that regulate the resolution of pulmonary edema in both the normal and the injured lung. Although the physiological mechanisms responsible for the formation of pulmonary edema were identified by 1980, the mechanisms that explain the resolution of pulmonary edema were not well understood at that time. However, in the 1980s several investigators provided novel evidence that the primary mechanism for removal of alveolar edema fluid depended on active ion transport across the alveolar epithelium. Sodium enters through apical channels, primarily the epithelial sodium channel, and is pumped into the lung interstitium by basolaterally located Na/K-ATPase, thus creating a local osmotic gradient to reabsorb the water fraction of the edema fluid from the airspaces of the lungs. The resolution of alveolar edema across the normally tight epithelial barrier can be up-regulated by cyclic adenosine monophosphate (cAMP)-dependent mechanisms through adrenergic or dopamine receptor stimulation, and by several cAMP-independent mechanisms, including glucocorticoids, thyroid hormone, dopamine, and growth factors. Whereas resolution of alveolar edema in cardiogenic pulmonary edema can be rapid, the rate of edema resolution in most patients with acute respiratory distress syndrome (ARDS) is markedly impaired, a finding that correlates with higher mortality. Several mechanisms impair the resolution of alveolar edema in ARDS, including cell injury from unfavorable ventilator strategies or pathogens, hypoxia, cytokines, and oxidative stress. In patients with severe ARDS, alveolar epithelial cell death is a major mechanism that prevents the resolution of lung edema.


A unitunnel technique for arthroscopic anterior cruciate ligament reconstruction.
Anterior cruciate ligament reconstruction can now be accomplished by arthroscopic surgery. With the introduction of a new arthroscopic drill guide and accessory instrumentation, a single tibiofemoral tunnel is created through which an anterior cruciate ligament graft can be anatomically and isometrically positioned. The appropriate graft is secured intraarticularly inside the femoral portion of the tunnel. Any type of graft structure can be used with this technique by varying the diameter of the tunnel or the depth of penetration into or through the lateral femoral condyle as needed. Correct anatomic and isometric positioning of the anterior cruciate ligament graft by this method have been confirmed on cadaver studies, by direct arthroscopic visualization and testing at the time of surgery, and on postoperative radiographs. The procedure has been performed on 45 patients. The longest follow-up is 48 months; the mean follow-up is 26.3 months. Early postoperative clinical results are most encouraging, with the pivot shift test being universally negative. The unitunnel technique for arthroscopic anterior cruciate ligament reconstruction has greatly reduced surgical morbidity without apparently compromising the results of surgery. The technique could become a standard procedure for the experienced arthroscopist and knee surgeon.


Application of a Fourier Transform Infrared (FTIR) Principal Component Regression (PCR) Chemometric Method for the Quantification of Respirable Crystalline Silica (Quartz), Kaolinite, and Coal in Coal Mine Dusts from Australia, UK, and South Africa.
This article describes the approach used to assess the performance of a Fourier transform infrared (FTIR) and principal component regression (PCR) chemometric method when measuring respirable quartz, kaolinite, and coal in samples from a variety of mines from different countries; relative to target assigned values determined using X-ray diffraction (XRD). For comparison, FTIR results using the partial least squares regression (PLSR) method are also available. Bulk dusts from 10 Australian mines were scanned using XRD and grouped into three sets based on the levels of quartz, kaolinite, and feldspar within their crystalline mineral composition. Prediction samples were generated from 5 of these Australian mine dusts, Durrans coal dust, 2 mine dusts from the UK, and a single South African mine dust (71 samples in total) by collecting the aerosolized respirable dust onto 25-mm diameter polyvinylchloride filters using the Safety in Mines Personal Dust Sampler (SIMPEDS) operating at 2.2 l min-1. The predicted values from the FTIR chemometric methods were compared with assigned target values determined using a direct on-aerosol filter XRD analysis method described in Method for the Determination of Hazardous Substances (MDHS) 101. Limits of detection (LOD) and uncertainty values for each analyte were calculated from a linear regression between target and predicted values. The uncertainty was determined using the calibration uncertainty equation for an unweighted regression. FTIR results from PCR and PLSR are very similar. For the PCR method, the LOD for quartz, kaolinite, and coal were 5, 25, and 71 µg, respectively. For quartz, an LOD of 5 µg corresponds to an airborne quartz concentration of 10 µg m-3, assuming a 4-h sampling time and collection flow rate of 2.2 l min-1. The FTIR measurement met the expected performance criteria outlined in ISO 20581 when sampling quartz for more than 4 h using a flow rate of 2.2 l min-1 at a concentration of 0.1 mg m-3 (100 µg m-3), the current workplace exposure limit in Great Britain. This method met the same performance criteria when measuring exposures at the Australian Workplace Exposure Standard (WES) concentration of 0.05 mg m-3, although in this case a sampling period greater than 8 h was needed.


Neobraclactones A-C, three unprecedented chaise longue-shaped xanthones from Garcinia bracteata.
Neobraclactones A-C (1-3), featuring an unprecedented further rearranged prenylxanthone skeleton with a unique octahydro-2H-1,3-dioxacyclopenta[c,d]inden-2-one scaffold, along with their biosynthesis-related known compound neobractatin (4), were isolated from the leaves of Garcinia bracteata. Their structures with absolute configurations were determined by extensive analyses of spectroscopic data and ECD calculations. Compounds 1 and 2 showed significant growth inhibition activities against the human leukaemia HL-60 and K562 cell lines with GI50 values from 0.40 to 0.86 μM.


Scaffold proteins in mammalian MAP kinase cascades.
The mitogen-activated protein kinase (MAPK) signaling pathway, which is conserved from yeast to humans, is activated in response to a variety of extra- and intracellular stimuli, and plays key roles in multiple cellular processes, including proliferation, differentiation, and apoptosis. The MAPK pathway transmits its signal through the sequential phosphorylation of MAPK kinase kinase to MAPK kinase to MAPK. Specific and efficient activation of the MAPK cascades is crucial for proper cellular responses to stimuli. As shown in yeast, the mammalian MAPK signaling system may also employ scaffold proteins, in part, to organize the MAPK signaling components into functional MAPK modules, thereby enabling the efficient activation of specific MAPK pathways. This review article describes recent advances in the study of potential mammalian scaffold proteins that may help us understand the complex regulation, including the spatial and temporal control, of the mammalian MAPK signaling pathways.


Framework for the assessment of the safety culture in the oil and gas industry.
AbstractApproaches to safety culture assessment may have many limits if supported exclusively by quantitative methods. Based on that, a research team developed a quantitative-qualitative approach to assess the maturity of the safety culture on an oil platform. To that end, the team sought to develop and test a method consisting of an initial ethnographic phase followed by 4 other distinct phases: definition of homogeneous groups; production of customized questionnaires; quantitative evaluation; and qualitative assessment. The results show the emergence of trends, from pre-defined themes in the safety culture to specific levels of maturity for each of the homogeneous groups. At the same time, it was possible to perceive that the maturity level of the groups is defined from the daily work practices developed by each one of them. This experience allowed us to propose a framework for assessing the maturity levels of safety culture for the oil and gas industry.


[Effect of α -1,2 fucosyltransferase gene 682A> G and 547_552delAG mutations on the activity of fucosyltransferase].
To explore the effect of α -1,2 fucosyltransferase (FUT1) gene 682A> G and 547_552delAG mutations on the expression of FUT1 mRNA and activity of α -1,2 fucosyltransferase. Recombinant expression vectors of FUT1 682A> G and FUT1 547_552delAG were constructed and transfected into COS-7 cells for stable expression screening. Expression of FUT1 mRNA was determined using real-time quantitative PCR. The activity of FUT1 was measured with high-performance liquid chromatography. Stably transfected COS-7 cells with wild type FUT1, FUT1 682A> G and FUT1 547_552delAG were respectively obtained. The FUT1 mRNA level of transfected cells with 682A> G and 547_552delAG recombination vectors have measured 101.69% and 102.79% compared with that of wild type FUT1 transfected cells. A specific protein band with about 46 kD was confirmed in the 682A> G transfected cell lysates by SDS-PAGE electrophoresis and Western blotting with 6× His Tag antibody. Similar protein was not identified in the 547_552delAG cells lysates. Enzymes activity of FUT1 682A> G has measured 61.01% compared with wild type FUT1 protein, whilst the activity of FUT1 547_557delAG was completely abolished. FUT1 682A> G and 547_552delAG mutations do not affect the transcript efficiency, although various mutations have different impact on the enzyme's activity.