Association between pregnancy and acute appendicitis in South Korea: a population-based, cross-sectional study.
To estimate the prevalence of acute appendicitis and the relationship between pregnancy and acute appendicitis among South Korean women in 2009. This was a cross-sectional study over 1 year period using a national registry data. We analyzed a national patient sample (n = 1,116,040) from a database complied by the South Korean National Health Insurance in 2009. We identified 15,974 cases of acute appendicitis from 2009. The prevalence rate of acute appendicitis was 228 ± 2 per 100,000 persons. The prevalence in men was higher than in women. The peak prevalence of the disease in both genders occurred in patients aged 10 to 14 years. After that, prevalence declined with age. The prevalence of acute appendicitis in women aged 20 to 39 years was negatively associated with age and pregnancy (P < 0.001) but was not associated with socioeconomic status. The prevalence of perforated appendicitis cases by age is represented by a U-shaped curve. The prevalence was highest in people less than five years of age and in people older than 60 years. We found that the prevalence of acute appendicitis decreased with increasing age after early teens, and that the prevalence of acute appendicitis in pregnant women was lower than in nonpregnant women.


Multiple mechanisms of methicillin resistance and improved methods for detection in clinical isolates of Staphylococcus aureus.
The mec gene of a number of clinical methicillin-resistant Staphylococcus aureus isolates exhibiting a variety of heterogeneous expression modes was selectively inactivated by allelic replacement mutagenesis. While the resistance level of each of the transformants was reduced, the methicillin MIC for these transformants was well above the MIC for susceptible laboratory strains of S. aureus and was similar to the methicillin MIC for many contemporary clinical isolates which did not react with the mec-specific DNA probe but which showed a low or borderline level of resistance to methicillin. A number of those strains had no detectable beta-lactamase, and for about half of the isolates that did carry plasmid-borne beta-lactamase, elimination of the plasmid caused only partial reduction of the methicillin MIC or no reduction at all. The findings suggest that many contemporary strains of staphylococci harbor a combination of at least three distinct beta-lactam resistance mechanisms: (i) the mechanism related to the acquisition of the foreign mec gene and (ii) a beta-lactamase-dependent and (iii) a beta-lactamase-independent mechanism, each one of which can provide a certain degree of resistance against penicillinase-resistant beta-lactam antibiotics.


Hemodynamic effects of arginine vasopressin in conscious water-deprived rats.
By means of a specific antagonist [d(CH2)5AVP] of the vasoconstrictor activity of arginine vasopressin (AVP), we studied whether the vasoconstrictor effect of AVP contributed to the blood pressure control during water deprivation in conscious rats. After 24 h of dehydration plasma AVP rose from 3.5 +/- 0.5 to 11.2 +/- 2.0 fmol/ml. Intravenous injection of 5 micrograms/kg d(CH2)5AVP reduced total peripheral resistance. Since cardiac output rose simultaneously, mean arterial blood pressure remained unchanged. In rats with sinoaortic deafferentation (SAD) 4 wk before water deprivation, d(CH2)5AVP caused a reduction of total peripheral resistance and of mean arterial pressure, whereas cardiac output remained unchanged. Consequently, mean arterial pressure fell. No hemodynamic changes were observed in hydrated control rats with and without SAD. It is concluded that the vasoconstrictor activity of AVP plays an important role in maintaining blood pressure during water deprivation in conscious rats. After AVP blockade, arterial pressure fell only in SAD rats as intact rats maintain arterial pressure via acute increase cardiac output.


Physiologic, metabolic and mediator responses in posttrauma ARDS and sepsis: is oxygen debt a critical initiating factor?
Posttrauma adult respiratory distress syndrome (ARDS) and sepsis initiate complex humoral and cellular inflammatory responses that initially effect the microvascular system, but rapidly extend to involve and modulate the solid organ metabolic response. It is discussed whether the interaction between these cellular processes and the organs which they involve appear to be initiated by the trauma induced oxygen debt.


Survival of Bacteria in Respiratory Protective Filters.
The aim of this study was to estimate the susceptibility of Staphylococcus hominis bacteria to the bacteriostatic agent in respiratory protective filters. Four types of filter media of different characteristics were tested. The number of bacteria was estimated by a culture-based method. It was proved that in treated filters the number of S. hominis was significantly reduced, even below the detection limit, while in untreated material bacteria were able to grow and multiply up to 100-fold within 8 hours. There was no correlation between filter structure and changes in the number of bacterial cells.


Environmental enrichment ameliorates perinatal brain injury and promotes functional white matter recovery.
Hypoxic damage to the developing brain due to preterm birth causes many anatomical changes, including damage to the periventricular white matter. This results in the loss of glial cells, significant disruptions in myelination, and thereby cognitive and behavioral disabilities seen throughout life. Encouragingly, these neurological morbidities can be improved by environmental factors; however, the underlying cellular mechanisms remain unknown. We found that early and continuous environmental enrichment selectively enhances endogenous repair of the developing white matter by promoting oligodendroglial maturation, myelination, and functional recovery after perinatal brain injury. These effects require increased exposure to socialization, physical activity, and cognitive enhancement of surroundings-a complete enriched environment. Using RNA-sequencing, we identified oligodendroglial-specific responses to hypoxic brain injury, and uncovered molecular mechanisms involved in enrichment-induced recovery. Together, these results indicate that myelin plasticity induced by modulation of the neonatal environment can be targeted as a therapeutic strategy for preterm birth.


Evaluating the power consumption of wireless sensor network applications using models.
Power consumption is the main concern in developing Wireless Sensor Network (WSN) applications. Consequently, several strategies have been proposed for investigating the power consumption of this kind of application. These strategies can help to predict the WSN lifetime, provide recommendations to application developers and may optimize the energy consumed by the WSN applications. While measurement is a known and precise strategy for power consumption evaluation, it is very costly, tedious and may be unfeasible considering the (usual) large number of WSN nodes. Furthermore, due to the inherent dynamism of WSNs, the instrumentation required by measurement techniques makes difficult their use in several different scenarios. In this context, this paper presents an approach for evaluating the power consumption of WSN applications by using simulation models along with a set of tools to automate the proposed approach. Starting from a programming language code, we automatically generate consumption models used to predict the power consumption of WSN applications. In order to evaluate the proposed approach, we compare the results obtained by using the generated models against ones obtained by measurement.


The Mediterranean diet and risk of colorectal cancer in the UK Women's Cohort Study.
Evidence from epidemiological studies investigating associations between adherence to the Mediterranean diet and colorectal cancer is inconsistent. The aim of this study is to assess in the UK Women's Cohort Study whether adherence to the Mediterranean dietary pattern is associated with reduced incidence of cancers of the colon and rectum. A total of 35 372 women were followed for a median of 17.4 years. A 10-component score indicating adherence to the Mediterranean diet was generated for each cohort participant, using a 217-item food frequency questionnaire. The Mediterranean diet score ranged from 0 for minimal adherence to 10 for maximal adherence. Cox proportional hazards regression was used to provide adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for colon and rectal cancer risk. A total of 465 incident colorectal cancer cases were documented. In the multivariable adjusted model, the test for trend was positive (HR = 0.88, 95% CI: 0.78 to 0.99; Ptrend = 0.03) for a 2-point increment in the Mediterranean diet score. For rectal cancer, a 2-point increment in the Mediterranean diet score resulted in an HR (95% CI) of 0.69 (0.56 to 0.86), whereas a 62% linear reduced risk (HR 0.38; 95% CI: 0.20 to 0.74; Ptrend < 0.001) was observed for women within the highest vs the lowest category of the MD score. Estimates for an association with colon cancer were weak (Ptrend = 0.41). Findings suggest that women adhering to a Mediterranean dietary pattern may have a lower risk of colorectal cancer, especially rectal cancer.


The Dynamic Occupational Therapy Cognitive Assessment for Children (DOTCA-Ch): a new instrument for assessing learning potential.
To describe the development and psychometric properties of the Dynamic Occupational Therapy Cognitive Assessment for Children (DOTCA-Ch), a dynamic criterion-referenced assessment of cognitive abilities and learning potential for children with cognitive and learning difficulties. A series of studies analyzed the age standards, criterion cutoff scores, and percentage of mediation cues required for typically developing children 6-12 years of age, as well as reliability and validity. MANOVA analyses determined four age groups that best fit the outcome data: 6-6.11, 7-8.11, 9-10.11, and 11-12 years. Criterion cutoff scores of 25% for at-risk and under 10% for deficient performance were obtained for each age group. Dynamic percentage scores were determined. Significant high interrater reliability and moderate to high internal consistency reliability were found. Construct validity was supported by comparing children with traumatic brain injury and learning disabilities to typically developing children, and ecological validity of children with attention deficit hyperactivity disorder by comparing performance on the DOTCA-Ch to the School Function Assessment. The DOTCA-Ch is a reliable and valid assessment that provides learning potential and can facilitate intervention for cognitive difficulties that manifest themselves in daily functions among school-age children.


Characterization by two-dimensional gel electrophoresis of host proteins whose synthesis is sustained or stimulated during the course of herpes simplex virus type 1 infection.
Herpes simplex virus type 1 (HSV-1) gene expression is concomitant with a selective shutoff of host protein synthesis. While the synthesis of the vast majority of cellular proteins is inhibited immediately after infection, several cellular proteins continue to be synthesized, even during the late phase of infection. Because these cellular proteins may intervene in the life cycle of the virus, we undertook two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) analyses to evaluate the proportion of cellular proteins that is represented by these particular proteins. Human cells were infected with HSV-1. At different times after infection, proteins were labeled with 35S just prior to harvesting. The rate of synthesis of a set of 183 acidic host proteins, as well as that of ribosomal proteins, was measured during the course of infection, after separation by 2-D PAGE. As expected, HSV-1 induces a strong inhibition of host protein synthesis immediately after infection. However, the synthesis of basic ribosomal proteins and that of an unexpected high proportion of the sub-set of cellular proteins analyzed is sustained or stimulated during HSV-1 infection. A 2-D PAGE analysis outlining the expression patterns of these proteins at different times of infection is presented.


Power, danger, and secrecy-A socio-cultural examination of menstrual waste management in urban Malawi.
Menstrual blood is not just a physical substance; it is laden with symbolism and often powerfully stigmatised. It is important to understand local perceptions and attitudes towards menstrual blood, as well as the preferred practices of menstruating women, in order to design appropriate sanitation and solid waste systems to support menstruation. Failure to take account of socio-cultural factors can jeopardise the effectiveness of such infrastructure. This study, conducted in Blantyre, Malawi, is a qualitative socio-cultural examination of how women manage and view menstruation. Thirty nine interviews, conducted with individuals and with small groups of friends, were carried out with thirty one women using pit latrines, flush toilets, and urine-diverting dry toilets in early 2019. Menstruation in Blantyre was found to be shrouded in secrecy because it was viewed as 'dirty', and therefore remained concealed. There was widespread anxiety about menstrual blood being used in ufiti (witchcraft), which affected how women used and disposed of their menstrual absorbents. At the same time, menstrual blood was also viewed as a powerful healing substance with uses in traditional medicine. The type of infrastructure required by women to support their menstruation depended on the type of menstrual absorbent used. Those using reusable cloth generally preferred a private bathroom with discreet drainage, whilst those using disposable pads needed a discreet and convenient disposal system. Increased preference for disposable pads over reusable cloth (particularly for younger women in education or employment) suggested that menstrual waste profiles of urban areas may be changing. Understanding these changing needs will be crucial for planning effective, sustainable waste disposal and sanitation infrastructure.


Perceiving time to collision activates the sensorimotor cortex.
The survival of many animals hinges upon their ability to avoid collisions with other animals or objects, or to precisely control the timing of collisions. Optical expansion provides a compelling impression of object approach and in principle can provide the basis for judgments of time to collision (TTC) [1]. It has been demonstrated that pigeons [2] and houseflies [3] have neural systems that can initiate rapid coordinated actions on the basis of optical expansion. In the case of humans, the linkage between judgments of TTC and coordinated action has not been established at a cortical level. Using functional magnetic resonance imaging (fMRI), we identified superior-parietal and motor-cortex areas that are selectively active during perceptual TTC judgments, some of which are normally involved in producing reach-to-grasp responses. These activations could not be attributed to actual movement of participants. We demonstrate that networks involved in the computational problem of extracting TTC from expansion information have close correspondence with the sensorimotor systems that would be involved in preparing a timed motor response, such as catching a ball or avoiding collision.


Sources of disconnection in neurocognitive aging: cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume.
Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19-79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the 3 imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function.


Genetic and epigenetic variations associated with adaptation to heterogeneous habitat conditions in a deciduous shrub.
Environmentally induced phenotypic plasticity is thought to play an important role in the adaption of plant populations to heterogeneous habitat conditions, and yet the importance of epigenetic variation as a mechanism of adaptive plasticity in natural plant populations still merits further research. In this study, we investigated populations of Vitex negundo var. heterophylla (Chinese chastetree) from adjacent habitat types at seven sampling sites. Using several functional traits, we detected a significant differentiation between habitat types. With amplified fragment length polymorphisms (AFLP) and methylation-sensitive AFLP (MSAP), we found relatively high levels of genetic and epigenetic diversity but very low genetic and epigenetic differences between habitats within sites. Bayesian clustering showed a remarkable habitat-related differentiation and more genetic loci associated with the habitat type than epigenetic, suggesting that the adaptation to the habitat is genetically based. However, we did not find any significant correlation between genetic or epigenetic variation and habitat using simple and partial Mantel tests. Moreover, we found no correlation between genetic and ecologically relevant phenotypic variation and a significant correlation between epigenetic and phenotypic variation. Although we did not find any direct relationship between epigenetic variation and habitat environment, our findings suggest that epigenetic variation may complement genetic variation as a source of functional phenotypic diversity associated with adaptation to the heterogeneous habitat in natural plant populations.


Exploring Factors Contributing to the Smoking Behaviour among Hong Kong Chinese Young Smokers during COVID-19 Pandemic: A Qualitative Study.
COVID-19 has significant impacts on young smokers in their smoking behaviors. This qualitative study summarises the lived experience of young smokers during COVID-19. Moreover, through their lived experience, we aim to understand how the COVID-19 pandemic influence tobacco use behaviours in this population. A purposive sampling of 48 smokers aged between 17-25 years old is individually interviewed for 30 to 45 min. All interviews are transcribed in verbatim and analysed by two researchers separately using Colaizzi's method of descriptive phenomenology. The results reveal the following six important themes, which could explain the mixed pattern of smoking behaviour changes in young smokers: (1) perceptions of COVID-19 and its association with smoking, (2) more time at home, (3) taking masks off to smoke, (4) the effects of COVID-19 on smokers' financial status and academic performance, (5) reduced social gatherings, and (6) restricted access to tobacco products. To conclude, this pandemic and the anti-pandemic measures, i.e., mask mandates, stay-at-home and work-from-home orders, and class suspension, result in both new obstacles and new advantages for smoking cessation among young people. More studies should be performed to monitor any transition of tobacco products and the trajectory of use in this population during this pandemic, thus informing public health policy making.


Electronically coarse-grained model for water.
We introduce an electronically coarse-grained description of water representing all long range, many-body electronic responses via an embedded quantum oscillator. Leading-order response coefficients and gas phase electrostatic moments are exactly reproduced. Molecular dynamics, using electronic path integral sampling, shows that this framework is sufficient for a realistic liquid to emerge naturally with transferability extending further to nonambient state points and to the free water surface. The model allows the strength of many-body dispersion and polarization to be adjusted independently and these are found to have significant effects on the condensed phase.


A role for acid-sensing ion channel 3, but not acid-sensing ion channel 2, in sensing dynamic mechanical stimuli.
Acid-sensing ion channels 2 and 3 (ASIC2 and ASIC3, respectively) have been implicated as putative mechanotransducers. Because mechanical hyperalgesia is a prominent consequence of nerve injury, we tested whether male and female ASIC2 or ASIC3 knockout mice have altered responses to mechanical and heat stimuli at baseline and during the 5 weeks after spinal nerve ligation. Age-matched, adult male and female ASIC2 knockout (n=21) and wild-type (WT; n=24) mice or ASIC3 knockout (n=20) and WT (n=19) mice were tested for sensitivity to natural stimuli before and after spinal nerve ligation surgery. All animals were first tested for baseline sensitivity to mechanical and heat stimuli and in a novel dynamic mechanical stimulation test. The same testing procedures were then repeated weekly after spinal nerve injury. Compared with their respective WT counterparts, ASIC2 and ASIC3 knockout mice had normal baseline sensitivity to standard mechanical and heat stimuli. However, when exposed to a novel stroking stimulus to test sensitivity to dynamic mechanical stimulation, ASIC3 knockout mice were significantly more sensitive than were WT mice. After spinal nerve ligation, ASIC2 and ASIC3 knockout mice developed mechanical and heat hyperalgesia comparable with that of their respective WT controls. In addition, in both experiments, female mice were more sensitive than male mice to heat at baseline and after the nerve injury. We conclude that ASIC2 and ASIC3 channels are not directly involved in the development or maintenance of neuropathic pain after spinal nerve ligation. However, the ASIC3 channel significantly modulates the sensing of dynamic mechanical stimuli in physiologic condition.


Impaired CD40L signaling is a cause of defective IL-12 and TNF-alpha production in Sézary syndrome: circumvention by hexameric soluble CD40L.
Sézary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma characterized by peripheral blood involvement, impaired cell-mediated immunity, and T-helper 1 (TH1) cytokine production. To understand the mechanism of these defects, we studied the expression and function of CD40L in peripheral blood mononuclear cells (PBMCs) of patients with SzS. We found that PBMCs of patients with SzS have a defect in interleukin-12 (IL-12) and tumor necrosis factor-alpha (TNF-alpha) production upon anti-CD3 stimulation and that tumor CD4+ T lymphocytes have a specific defect in CD40L induction after anti-CD3 ligation in vitro. This defect may explain the poor IL-12 production, because IL-12 production by anti-CD3-stimulated PBMCs was dependent on CD40L in healthy donors. The observed defect in tumor cell CD40L expression appears to be due to inappropriate T-cell signaling upon CD3 ligation, because expression of other T-cell activation antigens such as CD25, and to a lesser extent CD69, are also impaired on tumor cells. Importantly however, the inability of SzS PBMCs to appropriately produce IL-12 and TNF-alpha could be restored by recombinant hexameric CD40L. Taken together, our results demonstrate that impaired IL-12 and TNF-alpha production in SzS is associated with defective CD4+ T lymphocyte CD40L induction and indicate that CD40L may have therapeutic potential in SzS.


Quantitative tool for rapid disease mapping using optical coherence tomography images of azoxymethane-treated mouse colon.
Optical coherence tomography (OCT) can provide new insight into disease progression and therapy by enabling nondestructive, serial imaging of in vivo cancer models. In previous studies, we have shown the utility of endoscopic OCT for identifying adenomas in the azoxymethane-treated mouse model of colorectal cancer and tracking disease progression over time. Because of improved imaging speed made possible through Fourier domain imaging, three-dimensional imaging of the entire mouse colon is possible. Increased amounts of data can facilitate more accurate classification of tissue but require more time on the part of the researcher to sift through and identify relevant data. We present quantitative software for automatically identifying potentially diseased areas that can be used to create a two-dimensional "disease map" from a three-dimensional Fourier domain OCT data set. In addition to sensing inherent changes in tissue that occur during disease development, the algorithm is sensitive to exogeneous highly scattering gold nanoshells that can be targeted to disease biomarkers. The results of the algorithm were compared to histological diagnosis. The algorithm was then used to assess the ability of gold nanoshells targeted to epidermal growth factor receptor in vivo to enable functional OCT imaging.


[Analysis of c-kit gene mutations in gastrointestinal stromal tumors].
To define the frequency and spectrum of c-kit gene mutations in gastrointestinal stromal tumors (GIST). Fifty two cases of GIST and 28 cases of other tumors were examined for mutations in exon 11, 9 and 13 of c-kit gene using PCR amplification and DNA sequencing. Fourteen out of 25 malignant GIST (56%), while 2 of 27 benign and borderline GIST (7.4%) revealed mutations in exon 11 of c-kit gene (P < 0.01). Most of the mutations consisted of in-frame deletion or replication from 3 to 48 bp in heterozygous and homozygous fashions, but none of the mutations disrupted the downstream reading frame of the gene. Point mutation and deletion concentrated at 550 - 570 codons but replication clustered within 570 - 585 codons. The mutation pattern in recurrence tissues was the same as the primary ones. Normal tissues adjacent to GIST with or without c-kit gene mutations showed wild type c-kit gene sequence. No mutation was found in exon 9 and 13. Neither c-kit gene expression nor gene mutations was found in 3 leiomyomas, 8 leiomyosarcomas, 2 schwannomas, 2 intra-abdomenal fibromitoses and 8 adenocarcinomas. The mutations in exon 11 of c-kit gene might partially represent one of the molecular mechanisms of GIST. It can be used as a marker for distinguishing benignancy and malignancy of GIST. The mutations did not involve the reading frame. Except for long frame deletion, most mutations also did not affect protein expression. Mutation of c-kit gene in GIST provides a new genotypic marker to distinguish GIST from authentic leiomyomas, leiomyosarcomas, schwannomas and etc.


Perceived orientation in physical and virtual environments: changes in perceived orientation as a function of idiothetic information available.
Two experiments examined perceived spatial orientation in a small environment as a function of experiencing that environment under three conditions: real-world, desktop-display (DD), and head-mounted display (HMD). Across the three conditions, participants acquired two targets located on a perimeter surrounding them, and attempted to remember the relative locations of the targets. Subsequently, participants were tested on how accurately and consistently they could point in the remembered direction of a previously seen target. Results showed that participants were significantly more consistent in the real-world and HMD conditions than in the DD condition. Further, it is shown that the advantages observed in the HMD and real-world conditions were not simply due to nonspatial response strategies. These results suggest that the additional idiothetic information afforded in the real-world and HMD conditions is useful for orientation purposes in our presented task domain. Our results are relevant to interface design issues concerning tasks that require spatial search, navigation, and visualization.


Forage Ratio Analysis of the Southern House Mosquito in College Station, Texas.
Culex quinquefasciatus is the principal vector of West Nile virus (WNV) in the South Central United States, yet limited data on host utilization are available. We evaluated host utilization over a 3-month period in 2013 in a residential landscape in College Station, Texas. PCR sequencing of the mitochondrial cytochrome oxidase 1 gene permitted molecular identification of vertebrate bloodmeals to the species level. Forage ratio analysis identified bird species that were overutilized and underutilized by comparing community feeding index values to expected relative abundance values of bird species, derived from eBird data. Community feeding index values were also used in conjunction with reservoir competence data from the literature to generate reservoir capacity index values, a means of identifying relative importance of vertebrate reservoir hosts. Of 498 blood-engorged Cx. quinquefasciatus, 313 (62.9%) were identified to vertebrate species. The majority (95.5%) of bloodmeals originated from avian species with the remainder from mammals, but not humans. Northern mockingbird (Mimus polyglottos) was the principal host for mosquito feeding in June and July, but northern cardinal (Cardinalis cardinalis) became primary host in August. Forage ratio analysis revealed the overutilization of house finch (Haemorhous mexicanus), American robin (Turdus migratorius), northern mockingbird, northern cardinal, white-winged dove (Zenaida asiatica), and mourning dove (Zenaida macroura). Great-tailed grackle (Quiscalus mexicanus), blue jay (Cyanocitta cristata), and Carolina wren (Thryothorus ludovicianus) were under-utilized relative to availability. Reservoir capacity calculations suggested that northern mockingbird and northern cardinal were the principal amplifiers in the study area. These data identify the primary avian species contributing to the enzootic amplification of WNV in East-Central Texas and reveal that the heavy feeding on moderately competent hosts and no feeding on humans likely limit epidemics in this region.


Primary small-cell carcinoma of the stomach.
Primary small cell carcinoma of the stomach is an extremely rare tumor with only nine previously reported cases in the literature. Clinical behavior and prognosis are similar to small cell carcinomas of pulmonary origin. An additional case of a BI-year-old man with a gastric small cell carcinoma confined to the stomach is reported. The patient presented with an upper gastrointestinal bleed. A five centimeter ulcerated mass in the antrum was seen endoscopically and biopsied. At surgery the tumor appeared to be confined to the stomach and a subtotal gastrectomy was performed. The patient remains disease-free at 22 months. A review of nine other cases of small cell carcinoma of gastric origin reveals that most behave like their counterparts in the lung with rapid dissemination and death. However, like this patient, the only survivors for greater than one year are those amenable to surgical resection, implying that surgery has a roll in localized disease.


Transporter engineering in biomass utilization by yeast.
Biomass resources are attractive carbon sources for bioproduction because of their sustainability. Many studies have been performed using biomass resources to produce sugars as carbon sources for cell factories. Expression of biomass hydrolyzing enzymes in cell factories is an important approach for constructing biomass-utilizing bioprocesses because external addition of these enzymes is expensive. In particular, yeasts have been extensively engineered to be cell factories that directly utilize biomass because of their manageable responses to many genetic engineering tools, such as gene expression, deletion and editing. Biomass utilizing bioprocesses have also been developed using these genetic engineering tools to construct metabolic pathways. However, sugar input and product output from these cells are critical factors for improving bioproduction along with biomass utilization and metabolic pathways. Transporters are key components for efficient input and output activities. In this review, we focus on transporter engineering in yeast to enhance bioproduction from biomass resources.


Purine-induced depression of dorsal horn neurons in the cat spinal cord: enhancement by tachykinins.
The neurokinins, physalaemin, substance P, neurokinin A and bradykinin, were tested on the responses of single spinal neurons to the purines, adenosine 5'-triphosphate (ATP) and adenosine 5'-monophosphate and to GABA. Experiments were done on anaesthetized cats, recording extracellularly from functionally identified sensory neurons in the lumbar dorsal horn. All compounds were administered by iontophoresis. Neurokinins caused a slow, prolonged excitation which outlasted the period of application. Physalaemin was tested on responses to ATP in 24 units. In each case application of ATP caused either depression, excitation or a biphasic response when the application was not pre-conditioned by ejection of physalaemin. For 11 units, with ATP applications subthreshold to alter the on-going firing rate, such applications caused depression when they were preceded by administration of physalaemin. Three units were tested with ATP applications which caused the excitatory response; when the applications of ATP were preceded by ejection of physalaemin, there was then a depressant component in the response. In these 14 cases, the magnitude of the depression or of the depressant component of the response, was measured using currents which failed to produce depression in the absence of physalaemin ejection; the mean magnitude of this depression was 34.7 +/- 1.6% (+/- S.E.M.). With the 10 remaining units, responses to ATP were unaffected by application of physalaemin. The early components of the biphasic and excitatory responses were unaffected by physalaemin and hence it appeared to have a differential effect, enhancing only the depressant effects of ATP. The enhancement of depression was reversible, lasting up to 30 min following a single ejection. Neither control current nor glutamate mimicked the effect of physalaemin in the responses to application of ATP. The depressant response to adenosine 5'-monophosphate was also enhanced by physalaemin: ejections of adenosine 5'-monophosphate subthreshold to affect the on-going firing rate caused depression after physalaemin application in 3 of 8 units (average depression: 35.0 +/- 3.3%). On the other hand, depression induced by GABA was unaffected by physalaemin in every case (n = 8); in 4 of these cases GABA was tested on units for which purine-induced depression was enhanced by physalaemin. Thus, physalaemin preferentially affected depressant responses to ATP and to adenosine 5'-monophosphate.(ABSTRACT TRUNCATED AT 400 WORDS)


2021 Brazilian Thoracic Association recommendations for the management of severe asthma.
Advances in the understanding that severe asthma is a complex and heterogeneous disease and in the knowledge of the pathophysiology of asthma, with the identification of different phenotypes and endotypes, have allowed new approaches for the diagnosis and characterization of the disease and have resulted in relevant changes in pharmacological management. In this context, the definition of severe asthma has been established, being differentiated from difficult-to-control asthma. These recommendations address this topic and review advances in phenotyping, use of biomarkers, and new treatments for severe asthma. Emphasis is given to topics regarding personalized management of the patient and selection of biologicals, as well as the importance of evaluating the response to treatment. These recommendations apply to adults and children with severe asthma and are targeted at physicians involved in asthma treatment. A panel of 17 Brazilian pulmonologists was invited to review recent evidence on the diagnosis and management of severe asthma, adapting it to the Brazilian reality. Each of the experts was responsible for reviewing a topic or question relevant to the topic. In a second phase, four experts discussed and structured the texts produced, and, in the last phase, all experts reviewed and approved the present manuscript and its recommendations.


Clinical and molecular features and therapeutic perspectives of spinal muscular atrophy with respiratory distress type 1.
Spinal muscular atrophy with respiratory distress (SMARD1) is an autosomal recessive neuromuscular disease caused by mutations in the IGHMBP2 gene, encoding the immunoglobulin μ-binding protein 2, leading to motor neuron degeneration. It is a rare and fatal disease with an early onset in infancy in the majority of the cases. The main clinical features are muscular atrophy and diaphragmatic palsy, which requires prompt and permanent supportive ventilation. The human disease is recapitulated in the neuromuscular degeneration (nmd) mouse. No effective treatment is available yet, but novel therapeutical approaches tested on the nmd mouse, such as the use of neurotrophic factors and stem cell therapy, have shown positive effects. Gene therapy demonstrated effectiveness in SMA, being now at the stage of clinical trial in patients and therefore representing a possible treatment for SMARD1 as well. The significant advancement in understanding of both SMARD1 clinical spectrum and molecular mechanisms makes ground for a rapid translation of pre-clinical therapeutic strategies in humans.


Distribution of PACAP-38 in the central nervous system of various species determined by a novel radioimmunoassay.
Pituitary adenylate cyclase activating polypeptide (PACAP) occurs in two molecular forms: PACAP-38 and PACAP-27. Soon after the isolation and chemical characterization of PACAP, the first radioimmunoassay (RIA) methods have been developed, but it is a still rarely used laboratory technique in the field of PACAP research. The aim of the present study was to develop a novel, highly specific PACAP-38 assay to investigate the quantitative distribution of PACAP-38 in the central nervous system of various vertebrate species under the same technical and experimental conditions. Different areas of the brain and the spinal cord were removed from rats, chickens and fishes and the tissue samples were processed for PACAP-38 RIA. Our results indicate that the antiserum used in the RIA is C-terminal specific, without affinity for other members of the vasoactive intestinal polypeptide (VIP)/secretin/glucagon peptide family. The average ID50 value was 48.6+/-3.4 fmol/ml determined in 10 consecutive assays. Detection limit for PACAP-38 proved to be 2 fmol/ml. PACAP-38 immunoreactivity was present in the examined brain areas of each species studied, with highest concentration in the rat diencephalons. High levels of PACAP-38 were also detected in the rat telencephalon, followed by spinal cord and brainstem. The central nervous system of the fish also contained considerable concentrations of PACAP-38, whereas lowest concentrations were measured in the central nervous system of the chicken.


Variety matters: Diverse functions of monocyte subtypes in vascular inflammation and atherogenesis.
Monocytes are important mediators of the innate immunity by recognizing and attacking especially bacterial pathogens but also play crucial roles in various inflammatory diseases, including vascular inflammation and atherosclerosis. Maturation, differentiation and function of monocytes have been intensively explored for a long time in innumerable experimental and clinical studies. Monocytes do not represent a uniform cell type but could be further subdivided into subpopulations with distinct features and functions. Those subpopulations have been identified in experimental mouse models as well as in humans, albeit distinguished by different cell surface markers. While Ly6C is used for subpopulation differentiation in mice, corresponding human subsets are differentiated by CD14 and CD16. In this review, we specifically focused on new experimental insights from recent years mainly in regard to murine monocyte subpopulations and their roles in vascular inflammation und atherogenesis.


Emergencies in inflammatory bowel disease.
A review of acute emergencies in inflammatory bowel disease is presented. Caveats include prompt surgical drainage of loculated abscesses and aggressive management of bleeding or perforation. Adequate nutritional and immunologic assessment of all patients prior to surgery is paramount and has resulted in the widespread use of total parenteral nutrition. Aggressive medical therapy, particularly steroids, may be useful in "cooling down" cases of acute inflammation prior to surgery. This is particularly useful in Crohn's disease, in which recurrences abound and surgery has a significant degree of complication and recurrence. When urgent operation is necessary for acute ulcerative colitis, abdominal colectomy with ileostomy and preservation of the rectum is generally indicated. This will allow subsequent mucosal proctectomy and ileoanal anastomosis. When urgent colectomy is indicated for Crohn's colitis without rectal involvement, ileorectal anastomosis can be considered either as a primary or secondary procedure. If toxic megacolon is present, an initial trial of medical therapy is warranted in order to allow a single-staged operation to be performed electively.


Intraoperative hippocampal electrocorticography to predict the extent of hippocampal resection in temporal lobe epilepsy surgery.
Among the variety of surgical procedures that are performed for the treatment of medically refractory mesial temporal lobe epilepsy (TLE), no consensus exists as to how much of the hippocampus should be removed. Whether all patients require a maximal hippocampal resection has not yet been determined. At the University of Washington, all TLE operations are performed in a tailored fashion, guided by electrocorticography (ECoG). The amount of hippocampal resection is determined intraoperatively by the extent of interictal epileptiform abnormalities on ECoG recorded from that structure, resulting in a hippocampal resection that is individualized for each patient. Using this approach, the authors prospectively observed 140 consecutive patients who underwent surgery for mesial TLE with pathological diagnoses of either mesial temporal sclerosis with neuronal loss (MTS group) or mild gliosis without neuronal loss (non-MTS group) to determine whether the extent of hippocampal resection correlates with outcome when a tailored approach is used. Additionally, the authors analyzed whether the presence of residual interictal epileptiform activity on ECoG following mesial temporal resection predicts poorer seizure control. With at least 18 months of clinical follow up, 67% of the 140 patients were seizure free or had only a single postoperative seizure. There was no correlation between the size of the hippocampal resection and seizure control in the group as a whole or when stratified by pathological subtype. Using an intraoperatively tailored strategy, individuals with a larger hippocampal resection (> 2.5 cm) were not more likely to have seizure-free outcomes than patients with smaller resections (p = 0.9). Additionally, both MTS and non-MTS patients, in whom postoperative ECoG detected residual epileptiform hippocampal (but not cortical or parahippocampal) interictal activity following surgical resection, had significantly worse seizure outcomes (p = 0.01 in the MTS group; p = 0.002 in the non-MTS group). Intraoperative hippocampal ECoG can predict how much hippocampus should be removed to maximize seizure-free outcome, allowing for sparing of possibly functionally important hippocampus.


Oxidative Stress: A Suitable Therapeutic Target for Optic Nerve Diseases?
Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber's hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies.


[The applicability of auriculotherapy with needles or seeds to reduce stress in nursing professionals].
This clinical randomized trial was performed with the objective to evaluate the stress levels of the nursing staff of a hospital and analyze the effectiveness of auriculotherapy with needles and seeds. The 75 participants with mean (44/58.7%) and high (31/41.3%) scores according to the Stress Symptoms List were divided into groups (control, needles, and seeds), who received eight sessions on the Shenmen, Kidney and Brainstem points and were evaluated at the baseline, fourth and eighth sessions and on the 15-day follow-up session. The analysis of variance (ANOVA) showed significant differences among the groups at the third assessment (F=3.963/P=0.023) and follow-up (F=6.136/P=0.003). These differences occurred between the control and needle groups. The 'seeds' and needles groups both showed differences (p<0.05) at the second assessment when compared within the same group. In conclusion, auriculotherapy reduced the stress in the nursing staff, with needles showing better results than seeds for high scores, maintaining the effects for 15 days.


The assessment of communication skills in palliative medicine: a comparison of the scores of examiners and simulated patients.
The Diploma in Palliative Medicine was established in 1991 and included communication skills as a major part of the curriculum. In order to assess the efficacy of doctors' communication skills in the Diploma examination, an assessment tool was developed based on the modified Prevara Score. Simulated (actor) patients are used for the consultation in the examination; the doctors' performance is assessed independently by the examiner and by the actor. This provides an opportunity to consider the methods used for describing agreement between raters. There was high correlation between examiners' and actors' scores and high acceptability of the scoring method. However, satisfactory agreement in terms of the mean differences between scores and their standard deviation between examiners' and actors' scores was not achieved. We have found the simulated patient interview to be a useful teaching and assessment tool. The good correlation between the observer's (examiner) and the recipient's (actor-patient) perception of the doctor's interviewing skills provides evidence of the validity of the assessment. However the actor-patients' ratings tended to be higher and the two groups of assessors could not be used interchangeably. We conclude that actor-patients are of value in teaching and in assessing the communication skills of doctors but produce different scores to clinical examiners.


Mechanisms and Control of Self-Emulsification upon Freezing and Melting of Dispersed Alkane Drops.
Emulsification requires drop breakage and creation of a large interfacial area between immiscible liquid phases. Usually, high-shear or high-pressure emulsification devices that generate heat and increase the emulsion temperature are used to obtain emulsions with micrometer and submicrometer droplets. Recently, we reported a new, efficient procedure of self-emulsification (Tcholakova et al. Nat. Commun. 2017, 8, 15012), which consists of one to several cycles of freezing and melting of predispersed alkane drops in a coarse oil-in-water emulsion. Within these freeze-thaw cycles of the dispersed drops, the latter burst spontaneously into hundreds and thousands of smaller droplets without using any mechanical agitation. Here, we clarify the main factors and mechanisms, which drive this self-emulsification process, by exploring systematically the effects of the oil and surfactant types, the cooling rate, and the initial drop size. We show that the typical size of the droplets, generated by this method, is controlled by the size of the structural domains formed in the cooling-freezing stage of the procedure. Depending on the leading mechanism, these could be the diameter of the fibers formed upon drop self-shaping or the size of the crystal domains formed at the moment of drop-freezing. Generally, surfactant tails that are 0-2 carbon atoms longer than the oil molecules are most appropriate to observe efficient self-emulsification. The specific requirements for the realization of different mechanisms are clarified and discussed. The relative efficiencies of the three different mechanisms, as a function of the droplet size and cooling procedure, are compared in controlled experiments to provide guidance for understanding and further optimization and scale-up of this self-emulsification process.


Use of female controlled microbicidal products for HIV risk reduction.
Many over-the-counter microbicidal contraceptive methods reduce the risk of acquiring sexually transmitted diseases. This pilot project compared the use of female controlled barrier methods in an extremely high-risk population of low-income drug abusing women following an intervention designed to promote HIV risk reduction and barrier use. An HIV transmission risk reduction interactive intervention emphasizing self-esteem, assertiveness and sexual negotiation was offered to 41 drug dependent women. Participants were randomly assigned to one of two conditions, a male and female condom condition or a male and female condom plus N-9 products (vaginal suppositories, film, gel) condition. Results from the three-month follow-up period suggest that there may be a synergistic effect of availability of multiple protective methods on the overall rate of protective behaviours. The use of the male condom for penile/vaginal sex increased from 19% at study entry to 27% during the three-month follow-up period. The total protected sexual episode rate, calculated to include use of the other protective barriers distributed, was 60%. Thus, the condom use rate was not found to decrease because of the availability of alternative methods of protection. Future research should address the use of microbicidal products to empower women to prevent STD/HIV transmission.


The association of vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and gout.
About 2500 years ago, gout was observed by Hippocrates and many people suffered severe pain and deformity. Lifestyle and diet play a significant role in gout and serum uric acid levels. Epidemiological and research studies have supported this evidence. Many recommendations and guidelines from different parts of the world mention the impact of diet on gout. Recently, new research has shown associations between vitamin C, alcohol, coffee, tea, milk and yogurt with uric acid and the risk of gout. Our review summarizes recently published research regarding dietary impact on the risk of gout and serum uric acid levels.


On thermodynamic inconsistencies in several photosynthetic and solar cell models and how to fix them.
We analyze standard theoretical models of solar energy conversion developed to study solar cells and photosynthetic systems. We show that assuming the energy transfer to the reaction center/electric circuit is through a decay rate or "sink", contradicts the second law of thermodynamics. We put forward a thermodynamically consistent alternative by explicitly considering parts of the reaction center/electric circuit and by employing a Hamiltonian transfer. The predicted energy transfer by the new scheme differs from the one found using a decay rate, casting doubts on the validity of the conclusions obtained by models which include the latter.


A Prospective Pilot Study Comparing Rate of Processing Techniques in Autologous Fat Grafting.
Autologous fat grafting (AFG) is increasing in popularity to address a variety of defects. There is interest in developing techniques to harvest, process, and inject fat to improve clinical outcomes as well as operative efficiency. The purpose of this pilot study is to compare the rate of graft processing of two commercially available systems for graft preparation. Twenty consecutive cases using an active filtration system (system-AF) were observed followed by 20 consecutive cases using a passive filtration system (system-PF) to compare efficiency rate. Fat processing rate was quantified in milliliters/minute. Forty patients underwent AFG with no differences in patient characteristics between the groups. There was 1 incidence of palpable fat necrosis per group (5%). For all patients, this was the first fat grafting procedure; 20% of patients (n = 4 per group) had additional fat grafting. Overall, the rate of adipose tissue preparation was significantly higher with system-AF compared to system-PF (19.8 mL/min vs 5.3 mL/min, P ≤ 0.001). The resulting percent of graftable fat was comparable (AF: 41% vs PF: 42%; P = 0.83). Time and motion studies such as this provide a means to systematically document each of the steps involved in fat grafting in a reliable fashion. The authors demonstrate a significantly higher rate of lipoaspirate processing using an active filtration system compared to a passive system. Further large-scale studies of the efficacy and cost analysis of AFG are a necessary component of determining best practices in the field.


DNA damage-induced cohesion.
The protein complex Cohesin, forming protein-links that hold sister chromatids together, is at the heart of chromatid cohesion. Cohesion is important both for correct chromosome segregation and double-strand break (DSB) repair, making Cohesin central for the maintenance of genome stability. Until now, establishment of Cohesin links between chromatids has been shown to occur during DNA replication only. Recently it was however observed that in cells arrested in G2/M, DSB induction not only elicits chromosomal recruitment of Cohesin, but also formation of chromatid cohesion. The establishment of cohesion outside the period of replication opens a new field of investigation. Here we present results further supporting the formation of sister chromatid cohesion in response to DNA damage, and propose a model of how damage-induced cohesion could contribute to the linkage of chromatids during normal cell cycle progression.


Limitation of myocardial infarct size by a right ventricular assist device.
To evaluate the effects of an RVAD on myocardial ischemic injury during right coronary artery (RCA) ligation, a pneumatically driven pusher plate pump was inserted between the right atrium and pulmonary artery, and the RCA was ligated at its origin for two hr. There were 18 sheep, of which nine each served as the control and RVAD groups. Hemodynamic parameters and blood samples were collected from the coronary sinus. Area at risk and area of infarct were detected by gentian violet injection and triphenyltetrazolium (TTC) staining. Hemodynamic parameters (left ventricular systolic pressure (LVSP), cardiac output (CO], and creatine kinase levels in coronary sinus blood tended to be beneficial, to some degree, in the RVAD group. Electron microscopic examination revealed chromatin clumping and mitochondrial destruction, however this ultrastructural damage was more severe in the control group. The ratio of area of infarct to area at risk in the RVAD group was significantly less than that in the control group, being 20.25 +/- 6.93% vs. 47.24 +/- 10.53% (p less than 0.05). The infarct size induced by RCA occlusion was significantly reduced by the RVAD, due to the right ventricular unloading via reduced myocardial oxygen demand.


Protective effect of selenium on lung cancer in smelter workers.
A possible protective effect of selenium against lung cancer has been indicated in recent studies. Workers in copper smelters are exposed to a combination of airborne selenium and carcinogens. In this study lung tissue concentrations of selenium, antimony, arsenic, cadmium, chromium, cobalt, lanthanum, and lead from 76 dead copper smelter workers were compared with those of 15 controls from a rural area and 10 controls from an urban area. The mean exposure time for the dead workers was 31.2 years, and the mean retirement time after the end of exposure 7.2 years. Lung cancer appeared in the workers with the lowest selenium lung tissue levels (selenium median value 71 micrograms/kg wet weight), as compared with both the controls (rural group, median value 110; urban group, median value 136) and other causes of death among the workers (median value 158). The quotient between the metals and selenium was used for comparison: a high quotient indicating a low protective effect of selenium and vice versa. The median values of the quotients between antimony, arsenic, cadmium, lanthanum, lead, chromium, and cobalt versus selenium were all numerically higher among the cases of lung cancer, the first five significantly higher (p less than 0.05) in 28 of the 35 comparisons between the lung cancer group and all other groups of smelter workers and controls. The different lung metal concentrations for each person were weighted according to their carcinogenic potency (Crx4 + Asx3 + Cdx2 + Sbx1 + Cox1 + Lax1 + Pbx1) against their corresponding selenium concentrations. From these calculations the protective effect of selenium was even more pronounced.


The prevalence of colorectal adenomas in asymptomatic Korean men and women.
Colorectal cancer incidence is rapidly rising in many Asian countries, with rates approaching those of Western countries. This study aimed to evaluate the prevalence and trends of colorectal adenomas by age, sex, and risk strata in asymptomatic Koreans. Cross-sectional study of 19,372 consecutive participants aged 20 to 79 years undergoing screening colonoscopy at the Center for Health Promotion of the Samsung Medical Center in Korea from January 2006 to June 2009. Among participants at average risk, those without a history of colorectal polyps or a family history of colorectal cancer, the prevalence of colorectal adenomas and advanced adenomas were 34.5% and 3.1%, respectively, in men and 20.0% and 1.6%, respectively, in women. The prevalence of adenomas increased with age in both men and women, with a more marked increase for advanced adenoma. Participants with a family history of colorectal cancer or with a history of colorectal polyps had significantly higher prevalence of adenomas compared with participants of average risk (36.9% vs. 26.9%; age- and sex-adjusted prevalence ratio = 1.16; 95% confidence interval, 1.09-1.22). The prevalence of adenomas increased annually in both men and women. In this large study of asymptomatic Korean men and women participating in a colonoscopy screening program, the prevalence of colorectal adenomas was comparable and possibly higher than previously reported in Western countries. Cost-effectiveness studies investigating the optimal age for starting colonoscopy screening and etiological studies to identify the reasons for the increasing trend in colorectal adenomas in Koreans are needed.


NCI cooperative research and development agreements.
The Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) currently sponsors more than 160 Investigational New Drug applications (INDs), and is involved in approximately 1,600 active protocols. It is also currently involved in more than 50 collaborative agreements with pharmaceutical companies. These agreements consist of cooperative research and development agreements (CRADAs) and clinical trials agreements (CTAs). A CRADA is a detailed contract between the NCI and a pharmaceutical company for the clinical co-development of an investigational agent, and may include preclinical development that stipulates terms for a broader scope of research than that covered by a CTA. The CTEP/Investigational Drug Branch is currently involved in a number of oxaliplatin (Eloxatin) protocols under the CRADA program.


Alprazolam compared to diazepam and placebo in the treatment of anxiety.
Alprazolam was compared to diazepam and placebo in 235 outpatients suffering from manifest anxiety. In this 28-day double-blind study, alprazolam was more effective than placebo and essentially equivalent to diazepam in alleviating the symptoms of anxiety. However, alprazolam produced a markedly lower incidence of side effects than either diazepam or placebo. Of particular note, drowsiness was reported less than half as frequently by alprazolam patients than by diazepam patients. These results were achieved with an average daily dose of 1.5 mg alprazolam compared to 18.6 mg diazepam.


Benefits of screening for Chronic Kidney Disease.
The number of patients on renal replacement therapy has doubled every decade since 1980, and prevalence of chronic kidney disease (CKD) in the early stages is also markedly increased. In addition, CKD is a significant risk factor for cardiovascular morbidity and mortality. The only effective approach to this problem is prevention and early detection of CKD. In recent years, screening studies have been carried out in several countries. The findings have defined the scope of the problem and indicated which population groups are at risk of developing CKD. The most numerous are patients with hypertension and diabetes. Also, these studies have indicated that screening should include measurement of serum creatinine for eGFR as well as urine albumin. Early detection of CKD allows proper management that could slow down CKD progression, prevent cardiovascular and other comorbidities and enable timely initiation of dialysis. Screening for CKD could be best managed by partnership between primary care physicians and nephrologists. It is necessary to educate primary care physicians about CKD, its risk factors and associated co-morbidities. Although multiple benefits of screening for CKD are doubtless, the results obtained by screening should be interpreted with caution, bearing in mind that screening detects only markers of kidney disease but not the disease itself.


Germ-layer and lineage-restricted stem/progenitors regenerate the mouse digit tip.
The regrowth of amputated limbs and the distal tips of digits represent models of tissue regeneration in amphibians, fish and mice. For decades it had been assumed that limb regeneration derived from the blastema, an undifferentiated pluripotent cell population thought to be derived from mature cells via dedifferentiation. Here we show that a wide range of tissue stem/progenitor cells contribute towards the restoration of the mouse distal digit. Genetic fate mapping and clonal analysis of individual cells revealed that these stem cells are lineage restricted, mimicking digit growth during development. Transplantation of cyan-fluorescent-protein-expressing haematopoietic stem cells, and parabiosis between genetically marked mice, confirmed that the stem/progenitor cells are tissue resident, including the cells involved in angiogenesis. These results, combined with those from appendage regeneration in other vertebrate subphyla, collectively demonstrate that tissue stem cells rather than pluripotent blastema cells are an evolutionarily conserved cellular mode for limb regeneration after amputation.


Reducing the development of antibiotic resistance in critical care units.
Bacteria becoming resistant to an increasing number of antibiotic classes are a major problem at hospitals including critical care units worldwide. Awareness of this problem and the need to prevent the development of antibiotic resistance are very important, especially since very few new antibiotics will become available in the near future. This article gives an overview of the mechanisms of antibacterial resistance and actual resistance data worldwide of the most prevalent Gram positive (MRSA, VISA/VRSE and VRE) and Gram negative bacteria (Pseudomonas aeruginosa, Acinetobacter spp., ESBL producing Enterobacteriaceae and Stenotrophomonas maltophilia). Furthermore, strategies to reduce antibiotic resistance are reviewed. Most important is institution of infection control policies including guidelines on surveillance, isolation of colonized patients and contact precautions, hand hygiene, decolonization measures and environmental decontamination. Antimicrobial stewardship, or striking the balance between an optimal antibiotic treatment for a patient and a minimal risk of development of antibiotic resistance, is another important strategy. Finally, optimizing of antibiotic dosage regimens and thus avoiding underdosage is essential to avoid selection of the most resistant subpopulation of bacteria during antibiotic treatment. Intensive care units with knowledge of local epidemiology of resistance, an effective infection control program and antimicrobial stewardship policy tailored to their specific needs, and using optimal antibiotic dosing regimens have both locally decreased the risk of an outbreak with multi-resistant bacteria, and maybe even more important help to reduce the development of antibiotic resistance.


Elastic Versus Rigid Image Registration in Magnetic Resonance Imaging-transrectal Ultrasound Fusion Prostate Biopsy: A Systematic Review and Meta-analysis.
The main difference between the available magnetic resonance imaging-transrectal ultrasound (MRI-TRUS) fusion platforms for prostate biopsy is the method of image registration being either rigid or elastic. As elastic registration compensates for possible deformation caused by the introduction of an ultrasound probe for example, it is expected that it would perform better than rigid registration. The aim of this meta-analysis is to compare rigid with elastic registration by calculating the detection odds ratio (OR) for both subgroups. The detection OR is defined as the ratio of the odds of detecting clinically significant prostate cancer (csPCa) by MRI-TRUS fusion biopsy compared with systematic TRUS biopsy. Secondary objectives were the OR for any PCa and the OR after pooling both registration techniques. The electronic databases PubMed, Embase, and Cochrane were systematically searched for relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis Statement. Studies comparing MRI-TRUS fusion and systematic TRUS-guided biopsies in the same patient were included. The quality assessment of included studies was performed using the Quality Assessment of Diagnostic Accuracy Studies version 2. Eleven papers describing elastic and 10 describing rigid registration were included. Meta-analysis showed an OR of csPCa for elastic and rigid registration of 1.45 (95% confidence interval [CI]: 1.21-1.73, p<0.0001) and 1.40 (95% CI: 1.13-1.75, p=0.002), respectively. No significant difference was seen between the subgroups (p=0.83). Pooling subgroups resulted in an OR of 1.43 (95% CI: 1.25-1.63, p<0.00001). No significant difference was identified between rigid and elastic registration for MRI-TRUS fusion-guided biopsy in the detection of csPCa; however, both techniques detected more csPCa than TRUS-guided biopsy alone. We did not identify any significant differences in prostate cancer detection between two distinct magnetic resonance imaging-transrectal ultrasound fusion systems which vary in their method of compensating for prostate deformation.


High local substrate availability stabilizes a cooperative trait.
Cooperative behavior is widely spread in microbial populations. An example is the expression of an extracellular protease by the lactic acid bacterium Lactococcus lactis, which degrades milk proteins into free utilizable peptides that are essential to allow growth to high cell densities in milk. Cheating, protease-negative strains can invade the population and drive the protease-positive strain to extinction. By using multiple experimental approaches, as well as modeling population dynamics, we demonstrate that the persistence of the proteolytic trait is determined by the fraction of the generated peptides that can be captured by the cell before diffusing away from it. The mechanism described is likely to be relevant for the evolutionary stability of many extracellular substrate-degrading enzymes.


Simultaneous determination of 27 pesticides in corn and cow matrices by ultra-performance liquid chromatography-tandem mass spectrometry.
In this paper, we developed a sensitive UPLC-MS/MS method to determine pesticide residues in plant matrices (corn, fresh corn, fresh corn stover, old corn stover, and corn silage) and animal matrices (beef, fat, milk, milk fat, kidney, liver, and cow stomach) quantitatively. Twenty-seven pesticides were extracted with acetonitrile from all plant and animal matrices separately and purified with a mixture of primary secondary amine (PSA) and graphitized carbon black (GCB) or octadecylsilane (C18). The average recoveries of these compounds ranged from 60.7% to 118.2%, and the relative standard deviations were less than 20.0%. The limit of quantitation for all compounds was 0.01 mg kg-1 (for cyhalothrin and beta cypermethrin the LOQ was 0.02 mg kg-1). The establishment of multi-residue analysis methods for a variety of matrices can be used as a database for future method research. The results of this study are essential for calculating the transfer of pesticide residues from feed to animal products and for monitoring food safety, which will protect people's health and safety.


Altered T cell development in an animal model of multiple sclerosis.
Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system (CNS), leading to demyelination and axonal degeneration. Experimental autoimmune encephalomyelitis (EAE) is an animal model of MS that has significantly improved our understanding of MS. Studies have observed early thymic involution in MS patients, suggesting the potential involvement of the thymus in CNS autoimmunity. However, our knowledge of the thymus's role in autoimmune disorders affecting the CNS remains limited. In this study, we examined the effects of EAE induction on thymopoiesis and observed alterations in T cell development. These changes were characterized by increased apoptosis and decreased proliferation of thymocytes at the EAE peak stage. We also identified a blockade in the transition from CD4-CD8- double-negative thymocytes to CD4+CD8+ double-positive cells, as evidenced by the accumulation of double-negative stage 1 thymocytes at both the EAE onset and peak stages. Furthermore, positive selection was disrupted in the thymus of EAE mice at both stages, leading to an elevated proportion and number of CD4+CD8- and CD4-CD8+ single-positive cells. Meanwhile, we observed an augmented production of regulatory T cells in the thymus of EAE mice. Moreover, peripheral blood analysis of EAE mice at the onset stage showed expanded T cell subsets but not at the peak stage. We also observed altered expression patterns in thymus-derived CD4+CD8- and CD4-CD8+ single-positive cells between MS patients and healthy controls. Our findings demonstrate a modified T cell development in EAE/MS, providing valuable insights into the potential of modulating thymic function as a targeted therapeutic approach to MS/EAE.


Swiss nurses' knowledge related to health care reforms: an exploratory study.
This study examines health care reforms' implementation processes from the perspective of nurses' knowledge regarding the reforms. The research has been carried out in the Swiss (Canton Vaud) context, where health care reforms have been initiated, on the National (Federal) level, in 1996. Three research questions were formulated: (a) What is the level of nurses' knowledge regarding the basic principles of LAMal (Loi fédérale sur l'assurance maladie, Federal Health Insurance Law)? (b) What is the level of nurses' knowledge concerning the principles of health care reforms in Canton Vaud (NOPS, Nouvelles Orientations de la Politique Sanitaire)? and (c) Are there knowledge differences relating to employment setting (hospital, community, and education), nurses' roles (managerial vs. staff nurses) and level of education? The sample consisted of a total of 74 nurses. Of these, 20 were employed in the community, 30 in hospital settings and 24 worked in schools of nursing. The research tool utilized was 40-items nurses' knowledge questionnaire developed for the purpose of this study. Three knowledge subscales and a subscale of certainty were constructed. Overall, data showed a moderate to high mean level of knowledge (around 70% correct responses) on all knowledge scales considered. Community setting, managerial position, and a nonacademic nursing degree were all positively related to higher levels of reforms' knowledge. On the contrary, employment in a hospital setting and having a university degree had both negative impacts on achieving a high score of knowledge. Levels of certainty were significantly higher for LAMal than NOPS and for correct rather than for wrong responses.


Streptomyces bauhiniae sp. nov., isolated from tree bark of Bauhinia variegata Linn. in Thailand.
A novel actinomycete strain, Bv016T, belonging to the genus Streptomyces, was isolated from the bark of tree, Bauhinia variegata Linn., collected in Thailand. The taxonomic position of the strain was characterized by using a polyphasic approach. ll-Diaminopimelic acid, glucose, mannose, ribose and galactose were detected in its whole-cell hydrolysates. The N-acyl type of muramic acid was acetyl. The strain contained anteiso-C15 : 0, iso-C16 : 0, iso-C15 : 0 and iso-C14 : 0 as the major fatty acids and MK-9(H8), MK-9(H6) and MK-9(H4) as the major menaquinones. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside. The strain was closely related to Streptomyces griseoluteus JCM 4041T (98.4 %), Streptomyces seoulensis JCM 10116T (98.4 %) and Streptomyces recifensis JCM 4408T (98.2 %). The draft genome of Bv016T was 6.74 Mb with 5949 coding sequences with an average G+C content of 71.7 mol%. The ANIb and ANIm values of strain Bv016T were 94.1 and 95.2 %, respectively, and the digital DNA-DNA hybridization value was 60.6 % in comparison with the draft genome of S. griseoluteus JCM 4765T. The results of the taxonomic analysis suggested that strain Bv016T represented a novel species of the genus Streptomyces for which the name Streptomyces bauhiniae sp. nov. is proposed. The type strain is Bv016T (=JCM 33208T=TISTR 2645T).


Tenascin-C promotes microvascular cell migration and phosphorylation of focal adhesion kinase.
Enhanced expression of tenascin-C (TN-C) at the invasive edges of glioblastoma multiforme in close association with vascular sprouts, suggests a role for TN-C in microvascular cell migration. To test this hypothesis, we studied the migration of endothelial cells in vitro. In an aggregate migration assay, bovine retinal endothelial cells (BRECs) and human umbilical vein endothelial cells spread and migrated similarly on TN-C or fibronectin (FN). In contrast, U251 MG glioma cells migrated less on TN-C than on FN. Morphological features of U251 MG glioma cells on TN-C included poor cell spreading and short processes. In contrast, on FN, U251 MG glioma cells spread and exhibited long radial processes. Using a transmembrane migration assay, we observed that BREC adhesion was similar on TN-C or FN, whereas U251 MG glioma cells adhered better to FN than to TN-C. In addition, BRECs migrated more across the membrane toward regions coated with TN-C than FN, and conversely, U251 MG glioma cells migrated more toward FN than TN-C. Migration of endothelial and glioma cells toward TN-C or FN occurred in a dose-dependent manner and was strongly dependent on cell adhesion. In this assay, ultrastructural study revealed the migrating phenotype of the endothelial cells through the micropores of the membrane and their spread morphology on TN-C. Moreover, in situ hybridization revealed specific expression of TN-C in migrating microvascular cells in a cerebral microvascular ring assay. Finally in a phosphorylation assay, TN-C enhanced focal adhesion kinase phosphorylation of BRECs, but not of U251 MG glioma cells, and FN enhanced focal adhesion kinase phosphorylation of both BRECs and U251 MG cells. The expression of TN-C by migrating endothelial cells and the promotion of endothelial cell adhesion and migration by TN-C suggest a potential role for TN-C in pathological angiogenesis.


Prostaglandin E2 regulates tumor angiogenesis in prostate cancer.
In cancer management, the cyclooxygenase (COX)-targeted approach has shown great promise in anticancer therapeutics. However, the use of COX-2 inhibitors has side effects and health hazards; thus, targeting its major metabolite prostaglandin E(2) (PGE(2))-mediated signaling pathway might be a rational approach for the next generation of cancer management. Recent studies on several in vitro and in vivo models have revealed that elevated expression of COX-2 correlates with prostate tumor growth and angiogenesis. In this study, we have shown the in-depth molecular mechanism and the PGE(2) activation of the epidermal growth factor receptor and beta3 integrin through E prostanoid 2 (EP2)-mediated and EP4-mediated pathways, which lead to activator protein-1 (AP-1) activation. Moreover, PGE(2) also induces activating transcription factor-4 (ATF-4) activation and stimulates cross-talk between ATF-4 and AP-1, which is unidirectional toward AP-1, which leads to the increased expressions of urokinase-type plasminogen activator and vascular endothelial growth factor and, eventually, regulates prostate tumor cell motility. In vivo Matrigel angiogenesis assay data revealed that PGE(2) induces angiogenesis through EP2 and EP4. Human prostate cancer specimen analysis also supported our in vitro and in vivo studies. Our data suggest that targeting PGE(2) signaling pathway (i.e., blocking EP2 and EP4 receptors) might be a rational therapeutic approach for overcoming the side effects of COX-2 inhibitors and that this might be a novel strategy for the next generation of prostate cancer management.


Epoxomicin Sensitizes Resistant Osteosarcoma Cells to TRAIL Induced Apoptosis.
Osteosarcoma (OS) is the second most common primary malign bone neoplasm after multiple myeloma. Despite systemic chemotherapy, OS may give rise to local recurrences and metastases. Resistance to chemotherapy is not rare and is likely to occur in a high number of patients. Novel therapeutic approaches are required in order to efficiently treat osteosarcoma. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and proteasome inhibitors (epoxomicin, MG132, bortezomib) represent new promising approaches in cancer treatment. The aim of our study is to elucidate the effects of epoxomicin alone or in combination with TRAIL in two TRAIL-resistant OS cell lines, Saos-2 and MG-63 namely. We determined the cytotoxic effects of epoxomicin and/or TRAIL on these two types of OS cells using dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) test and measured apoptosis markers such as pro-apoptotic Bax levels and caspase-3, -8, -9 activities. We used TUNEL assay to demonstrate apoptosis. We investigated dose and time dependent survival rates of OS cells and determined LD50 doses of epoxomicin and TRAIL on OS cell viability after 24, 48, and 72 hour incubations. Concurrent incubation with TRAIL and epoxomicin for 24 hour significantly increased caspase-3, caspase-8, caspase-9 activities and Bax protein levels. Our study demonstrated that the combination of TRAIL with epoxomicin enhances apoptosis, and overcomes TRAIL resistance, denoting promising results for OS therapy in the future.


Methicillin-resistant staphylococcus aureus infections among competitive sports participants--Colorado, Indiana, Pennsylvania, and Los Angeles County, 2000-2003.
Although outbreaks of methicillin-resistant Staphylococcus aureus (MRSA) usually have been associated with health-care institutions, MRSA is emerging as a cause of skin infections in the community. This report summarizes several reported clusters of skin and soft tissue infections associated with MRSA among participants in competitive sports and identifies possible risk factors for infection (e.g., physical contact, skin damage, and sharing of equipment or clothing). The findings underscore 1) the potential for MRSA infections among sports participants; 2) the need for health-care providers to be aware that skin and soft tissue infections occurring in these settings might be caused by MRSA; and 3) the importance of implementing prevention measures by players, coaches, parents, and school and team administrators.


Acyl-CoA oxidase 1 from Arabidopsis thaliana. Structure of a key enzyme in plant lipid metabolism.
The peroxisomal acyl-CoA oxidase family plays an essential role in lipid metabolism by catalyzing the conversion of acyl-CoA into trans-2-enoyl-CoA during fatty acid beta-oxidation. Here, we report the X-ray structure of the FAD-containing Arabidopsis thaliana acyl-CoA oxidase 1 (ACX1), the first three-dimensional structure of a plant acyl-CoA oxidase. Like other acyl-CoA oxidases, the enzyme is a dimer and it has a fold resembling that of mammalian acyl-CoA oxidase. A comparative analysis including mammalian acyl-CoA oxidase and the related tetrameric mitochondrial acyl-CoA dehydrogenases reveals a substrate-binding architecture that explains the observed preference for long-chained, mono-unsaturated substrates in ACX1. Two anions are found at the ACX1 dimer interface and for the first time the presence of a disulfide bridge in a peroxisomal protein has been observed. The functional differences between the peroxisomal acyl-CoA oxidases and the mitochondrial acyl-CoA dehydrogenases are attributed to structural differences in the FAD environments.


Evaluating REDCap as the Central Data Collection Tool for the Hamburg City Health Study.
The collection of examination data for large clinical studies is often done with proprietary systems, which are accompanied by several disadvantages such as high cost and low flexibility. With the use of open-source tools, these disadvantages can be overcome and thereby improve data collection as well as data quality. Here we exemplary use the data collection process of the Hamburg City Health Study (HCHS), carried out at the University Medical Center Hamburg-Eppendorf (UKE). We evaluated how the recording of the examination data can be converted from an established, proprietary electronic healthcare record (EHR) system to the free-to-use Research Electronic Data Capture (REDCap) software. For this purpose, a technical conversion of the EHR system is described first. Metafiles derived from the EHR system were used for REDCap electronic case report form (eCRF) building. The REDCap system was tested by HCHS study assistants via completion of self-developed tasks mimicking their everyday study life. Usability was quantitatively evaluated via the IBM Computer System Usability Questionnaire (CSUQ) and qualitatively assessed with a semi-structured interview. With the IBM CSUQ, the study assistants rated the usage of the basic REDCap system for HCHS examination data collection with an overall score of 4.39, which represents a medium acceptance. The interview feedback was used to formulate user stories to subsequently increase the administrative sovereignty and to conceptualize a REDCap HCHS information technology (IT) infrastructure. Our work aims to serve as a template for evaluating the feasibility of a conversion from a proprietary to a free-to-use data collection tool for large clinical studies such as the HCHS. REDCap has great potential, but extensions and an integration to the current IT infrastructure are required.


Galgravin Isolated from Piper kadsura Ameliorates Lipopolysaccharide (LPS)-Induced Endotoxemia in Mice.
Sepsis results from uncontrolled inflammation, characterized by cytokine storm and immunoparalysis. To assess whether galgravin, a natural lignan isolated from Piper kadsura, can be used to treat sepsis, models of bacterial lipopolysaccharide (LPS)-activated macrophages and LPS-induced endotoxemia mice were used. Galgravin suppressed NF-κB activation in LPS-activated RAW 264.7 macrophages without causing significant cytotoxicity, in which proinflammatory molecules like TNF-α, IL-6, iNOS, and COX-2 were downregulated. In addition, the expression of TNF-α and IL-6 was also suppressed by galgravin in LPS-activated murine bone marrow-derived macrophages. Moreover, galgravin significantly downregulated the mRNA expression of TNF-α, IL-6, and iNOS in the lungs and decreased TNF-α and IL-6 in the serum and IL-6 in the bronchoalveolar lavage fluid of LPS-challenged mice. The COX-2 expression in tissues, including the lung, liver, and kidney, as well as the lung alveolar hemorrhage, was also reduced by galgravin. The present study reveals the anti-inflammatory effects of galgravin in mouse models and implies its potential application in inflammation diseases.


Variable levels of bcl-2, bcl-x and bax mRNA in bladder cancer progression.
We investigated the expression of the anti-apoptotic genes bcl-2 and bcl-X and the pro-apoptotic gene bax in bladder tumors and normal samples from urinary bladder, using RT-PCR analysis. Bcl-2 mRNA was not detected in any of the normal samples, while it was found expressed in 66% of the low stage tumors and in 100% of the high stage tumors. Bax expression had an inverse progress, being present in 62% of the normal tissues examined, in 16% of the low stage tumors and in 14% of the high stage. Bcl-X gene expression was quite variable among all samples (37% in normal tissues, 50% in the low stage tumors and 14% in the high stage). bcl-X mRNA was only found in the isoform bcl-XL, with anti-apoptotic functions, whereas no sample expressed the isoform bcl-XS, which is known to suppress bcl-2 functions. Most samples expressing bcl-2 did not express bcl-X, and vice versa. These results, besides confirming the potential role of these genes in the pathogenesis of low stage bladder cancer strengthen the hypothesis concerning their possible interaction in the progression of disease.


Photodynamic therapy in the canine prostate using motexafin lutetium.
Our purpose was to determine the feasibility of comprehensive treatment of the canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex) and to evaluate the toxicity and tissue effects associated with this treatment. Twenty-five adult male beagles with normal prostate glands were given an i.v. injection of the second-generation photosensitizer Lu-Tex (2-6 mg/kg). An additional two dogs were used as controls and did not receive any photosensitizing drug. All 27 dogs underwent laparotomy to expose the prostate. Three hours postinjection, a total dose of 75-150 J/cm of 732 nm laser light was delivered interstitially and/or transurethrally to the prostate via cylindrical diffusing fibers. Dogs were euthanized between 2 days and 3 months after PDT. All subjects were monitored for clinical evidence of toxicity. Specimens were examined macroscopically and microscopically to characterize the tissue reaction and assess extent of tissue effect as a result of treatment. Interstitial and/or transurethral PDT were successfully delivered in all dogs with no perioperative complications. No clinical evidence of acute urinary obstruction or rectal bleeding was noted. At all dose levels, macroscopic and microscopic evaluation revealed a prostatic tissue reaction characterized initially (within 48 h) by inflammation and necrosis followed by fibrosis and glandular epithelial atrophy. Comprehensive treatment of the entire prostate could be achieved using the interstitial alone approach or combined transurethral and interstitial approach. The transurethral alone approach did not result in complete coverage of the prostate. Dogs receiving transurethral or combined interstitial and transurethral treatment developed erythema and urethral epithelial disruption at all dose levels. Those receiving combined treatment at the highest dose level (Lu-Tex 6 mg/kg, 150 J/cm light) developed urethral fistulae and peritonitis. Dogs treated with the interstitial alone approach were found to have the least amount of urethral damage. Comprehensive treatment of the canine prostate with Lu-Tex PDT is feasible using an interstitial alone or combined interstitial and transurethral approach. The interstitial alone technique results in the least amount of toxicity. The prostatic tissue reaction to treatment is characterized by initial inflammation and necrosis followed by fibrosis and glandular epithelial atrophy.


Biomechanics and running economy.
Running economy, which has traditionally been measured as the oxygen cost of running at a given velocity, has been accepted as the physiological criterion for 'efficient' performance and has been identified as a critical element of overall distance running performance. There is an intuitive link between running mechanics and energy cost of running, but research to date has not established a clear mechanical profile of an economic runner. It appears that through training, individuals are able to integrate and accommodate their own unique combination of dimensions and mechanical characteristics so that they arrive at a running motion which is most economical for them. Information in the literature suggests that biomechanical factors are likely to contribute to better economy in any runner. A variety of anthropometric dimensions could influence biomechanical effectiveness. These include: average or slightly smaller than average height for men and slightly greater than average height for women; high ponderal index and ectomorphic or ectomesomorphic physique; low percentage body fat; leg morphology which distributes mass closer to the hip joint; narrow pelvis and smaller than average feet. Gait patterns, kinematics and the kinetics of running may also be related to running economy. These factors include: stride length which is freely chosen over considerable running time; low vertical oscillation of body centre of mass; more acute knee angle during swing; less range of motion but greater angular velocity of plantar flexion during toe-off; arm motion of smaller amplitude; low peak ground reaction forces; faster rotation of shoulders in the transverse plane; greater angular excursion of the hips and shoulders about the polar axis in the transverse plane; and effective exploitation of stored elastic energy. Other factors which may improve running economy are: lightweight but well-cushioned shoes; more comprehensive training history; and the running surface of intermediate compliance. At the developmental level, this information might be useful in identifying athletes with favourable characteristics for economical distance running. At higher levels of competition, it is likely that 'natural selection' tends to eliminate athletes who failed to either inherit or develop characteristics which favour economy.


Integrated analysis of residue coevolution and protein structures capture key protein sectors in HIV-1 proteins.
HIV type 1 (HIV-1) is characterized by its rapid genetic evolution, leading to challenges in anti-HIV therapy. However, the sequence variations in HIV-1 proteins are not randomly distributed due to a combination of functional constraints and genetic drift. In this study, we examined patterns of sequence variability for evidence of linked sequence changes (termed as coevolution or covariation) in 15 HIV-1 proteins. It shows that the percentage of charged residues in the coevolving residues is significantly higher than that in all the HIV-1 proteins. Most of the coevolving residues are spatially proximal in the protein structures and tend to form relatively compact and independent units in the tertiary structures, termed as "protein sectors". These protein sectors are closely associated with anti-HIV drug resistance, T cell epitopes, and antibody binding sites. Finally, we explored candidate peptide inhibitors based on the protein sectors. Our results can establish an association between the coevolving residues and molecular functions of HIV-1 proteins, and then provide us with valuable knowledge of pathology of HIV-1 and therapeutics development.


[Effectiveness of collagen plasty in complex treatment of localized pyopneumothorax].
The work is based on an analysis of results of treatment of 25 patients with localized pleuro-pulmonary cavities by the methods of minor surgery. During abscessoscopy collagen was placed on the wound surface, the surface was filled with fibronectin and followed by active aspiration within 12-24 hours. In 20 (80%) patients the lung was expanded earlier. Five patients had no effect.


Revision of a Leaking Bleb With XEN Gel Stent Replacement.
Minimally invasive glaucoma surgery includes different devices which provide a less invasive and safer means of reducing intraocular pressure. The XEN Gel Stent (Allergan Inc., CA) is an ab interno procedure which creates a subconjunctival drainage pathway. It is a new surgical device and there is a paucity of data on complications and their management. We report a clinical case of a leaking bleb after XEN surgery managed by bleb revision, conjunctival suturing, and XEN replacement.


Systematic approaches to the prevention and management of patients with delirium.
Delirium is a common complication of acute illness in older people. Earlier and more reliable detection could be achieved by greater routine cognitive testing in older people. Research evidence suggests that episodes of delirium and duration of delirium could be reduced by about one third if systems of care that prioritized delirium risk factor amelioration were comprehensively adopted. Specialist delirium units have a place in leading and disseminating best practices. Health service regulators should consider monitoring delirium as an adverse health care outcome.


Investigation of the influence of different moisture levels on acrylamide formation/elimination reactions using multiresponse analysis.
The influence of water activity on the formation and elimination reactions of acrylamide was examined by means of multiresponse modeling on two different levels of complexity: basic equimolar asparagine-glucose systems and equimolar potato-based asparagine-glucose systems. To this end, model systems were first equilibrated to initial water activities in the range of 0.88-0.99 (corresponding roughly to the moisture gradient observed in French fries) and then heated at temperatures between 120 and 200 degrees C during different reaction times. For each sample, the concentration of acrylamide, glucose, asparagine, and aspartic acid was measured, as well as the extent of browning. A mechanistic model was proposed to model the five measured responses simultaneously. For both types of model systems, the model prediction was quite adequate, with the exception of the extent of browning, especially in the case of the potato-based model system. Moreover, the corresponding estimated kinetic parameters for acrylamide formation and elimination did not change significantly (based on a 95% confidence level) within the range of water activities tested, nor between the systems in the absence or presence of the potato matrix. The only remarkable difference was observed for the activation energy of acrylamide elimination, which was lower in the presence of the potato matrix, although not always significant. In general, these results confirm the generic nature of the model proposed and show that the influence of different moisture levels on acrylamide formation and elimination is minimal and that the addition of a potato matrix has little or no influence on the kinetic model and corresponding kinetic parameters.


Leveraging Population-Based Clinical Quantitative Phenotyping for Drug Repositioning.
Computational drug repositioning methods can scalably nominate approved drugs for new diseases, with reduced risk of unforeseen side effects. The majority of methods eschew individual-level phenotypes despite the promise of biomarker-driven repositioning. In this study, we propose a framework for discovering serendipitous interactions between drugs and routine clinical phenotypes in cross-sectional observational studies. Key to our strategy is the use of a healthy and nondiabetic population derived from the National Health and Nutrition Examination Survey, mitigating risk for confounding by indication. We combine complementary diagnostic phenotypes (fasting glucose and glucose response) and associate them with prescription drug usage. We then sought confirmation of phenotype-drug associations in unidentifiable member claims data from the Aetna Insurance company using a retrospective self-controlled case analysis approach. We identify bupropion as a plausible glucose lowering agent, suggesting that surveying otherwise healthy individuals in cross-sectional studies can discover new drug repositioning hypotheses that have applicability to longitudinal clinical practice.


What do we learn from neutrinos?
Each type of particle, by definition, is special. The special property of neutrinos is that they are penetrating. This has made their discovery and the understanding of their properties elusive, but it has also made them a useful tool in the study of particles and their interactions. In astrophysics, on account of this property, neutrinos provide an important means for energy transfer and permit insight into the interior of stars hidden to other radiation. The special conditions in space permit, in turn, the study of neutrino properties not possible in the laboratory.