Enhancing human spermine synthase activity by engineered mutations.
Spermine synthase (SMS) is an enzyme which function is to convert spermidine into spermine. It was shown that gene defects resulting in amino acid changes of the wild type SMS cause Snyder-Robinson syndrome, which is a mild-to-moderate mental disability associated with osteoporosis, facial asymmetry, thin habitus, hypotonia, and a nonspecific movement disorder. These disease-causing missense mutations were demonstrated, both in silico and in vitro, to affect the wild type function of SMS by either destabilizing the SMS dimer/monomer or directly affecting the hydrogen bond network of the active site of SMS. In contrast to these studies, here we report an artificial engineering of a more efficient SMS variant by transferring sequence information from another organism. It is confirmed experimentally that the variant, bearing four amino acid substitutions, is catalytically more active than the wild type. The increased functionality is attributed to enhanced monomer stability, lowering the pKa of proton donor catalytic residue, optimized spatial distribution of the electrostatic potential around the SMS with respect to substrates, and increase of the frequency of mechanical vibration of the clefts presumed to be the gates toward the active sites. The study demonstrates that wild type SMS is not particularly evolutionarily optimized with respect to the reaction spermidine → spermine. Having in mind that currently there are no variations (non-synonymous single nucleotide polymorphism, nsSNP) detected in healthy individuals, it can be speculated that the human SMS function is precisely tuned toward its wild type and any deviation is unwanted and disease-causing.


Epstein-Barr virus infection-induced inflammasome activation in human monocytes.
Inflammasomes are cytoplasmic sensors that regulate the activity of caspase-1 and the secretion of interleukin-1β (IL-1β) or interleukin-18 (IL-18) in response to foreign molecules, including viral pathogens. They are considered to be an important link between the innate and adaptive immune responses. However, the mechanism by which inflammasome activation occurs during primary Epstein-Barr virus (EBV) infection remains unknown. Human B lymphocytes and epithelial cells are major targets of EBV, although it can also infect a variety of other cell types. In this study, we found that EBV could infect primary human monocytes and the monocyte cell line, THP-1, inducing inflammasome activation. We incubated cell-free EBV with THP-1 cells or primary human monocytes, then confirmed EBV infection using confocal microscopy and flow cytometry. Lytic and latent EBV genes were detected by real-time RT-PCR in EBV-infected monocytes. EBV infection of THP-1 cells and primary human monocytes induced caspase-dependent IL-1β production, while EBV infection of B-cell or T-cell lines did not induce IL-1β production. To identify the sensor molecule responsible for inflammasome activation during EBV infection, we examined the mRNA and the protein levels of NLR family pyrin domain-containing 3 (NLRP3), absent in melanoma 2 (AIM2), and interferon-inducible protein 16 (IFI16). Increased AIM2 levels were observed in EBV-infected THP-1 cells and primary human monocytes, whereas levels of IFI16 and NLRP3 did not show remarkable change. Furthermore, knockdown of AIM2 by small interfering RNA attenuated caspase-1 activation. Taken together, our results suggest that EBV infection of human monocytes induces caspase-1-dependent IL-1β production, and that AIM2, acting as an inflammasome, is involved in this response.


Neutron scattering: good news for biotechnology.
In its application to biological systems, neutron scattering is still an emerging technology with a great deal of potential. A consequence of the native interaction between neutrons and biological samples is that the hydrogen isotopes (1)H and (2)H are most significant in dynamical and structural studies, respectively.


Power generation by high head water in a building using micro hydro turbine-a greener approach.
Demand for green energy production is arising all over the world. A lot of emphasis is laid in making the buildings green. Even a small amount of energy savings made contribute to saving the environment. In this study, an idea is proposed and studied to extract power from the high head water in the pipelines of a building. A building of height 15 m is considered for this study. Water flowing in the pipe has sufficient energy to run a micro hydro turbine. The feasibility of producing electrical energy from the energy of pipe water is found. The motivation is to find the feasibility of generating power using a low-cost turbine. The experimental setup consists of micro turbine of 135 mm diameter coupled to a 12-V DC generator; LEDs and resistors are employed to validate the results. The theoretical calculations were presented using the fundamental equations of fluid mechanics. The theoretical results are validated using experimental and numerical results using CFD simulation. In addition, exergy analysis has been carried out to quantify the irreversibilities during the process in the system.


What is new in cryptorchidism and hypospadias--a critical review on the testicular dysgenesis hypothesis.
It has been hypothesized that poor semen quality, testis cancer, undescended testis, and hypospadias are symptoms of one underlying entity--the testicular dysgenesis syndrome--leading to increasing male fertility impairment. Though testicular cancer has increased in many Western countries during the past 40 years, hypospadias rates have not changed with certainty over the same period. Also, recent studies demonstrate that sperm output may have declined in certain areas of Europe but is probably not declining across the globe as indicated by American studies. However, at the same time, there is increasing recognition of male infertility related to obesity and smoking. There is no certain evidence that the rates of undescended testes have been increasing with time during the last 50 years. In more than 95% of the cases, hypospadias is not associated with cryptorchidism, suggesting major differences in pathogenesis. Placental abnormality may occasionally cause both cryptorchidism and hypospadias, as it is also the case in many other congenital malformations. The findings of early orchidopexy lowering the risk of both infertility and testicular cancer suggest that the abnormal location exposes the cryptorchid testis to infertility and malignant transformation, rather than there being a primary abnormality. Statistically, 5% of testicular cancers only are caused by cryptorchidism. These data point to the complexity of pathogenic and epidemiologic features of each component and the difficulties in ascribing them to a single unifying process, such as testicular dysgenesis syndrome, particularly when so little is known of the actual mechanisms of disease.


Bacterial Genotoxins: Merging the DNA Damage Response into Infection Biology.
Bacterial genotoxins are unique among bacterial toxins as their molecular target is DNA. The consequence of intoxication or infection is induction of DNA breaks that, if not properly repaired, results in irreversible cell cycle arrest (senescence) or death of the target cells. At present, only three bacterial genotoxins have been identified. Two are protein toxins: the cytolethal distending toxin (CDT) family produced by a number of Gram-negative bacteria and the typhoid toxin produced by Salmonella enterica serovar Typhi. The third member, colibactin, is a peptide-polyketide genotoxin, produced by strains belonging to the phylogenetic group B2 of Escherichia coli. This review will present the cellular effects of acute and chronic intoxication or infection with the genotoxins-producing bacteria. The carcinogenic properties and the role of these effectors in the context of the host-microbe interaction will be discussed. We will further highlight the open questions that remain to be solved regarding the biology of this unusual family of bacterial toxins.


HNF1A gene p.I27L is associated with co-existing preeclampsia in gestational diabetes mellitus.
The association of the FTO gene and HNF1α gene on gestational diabetes mellitus (GDM) and preeclampsia remains unclear. This is the first study to examine whether HNF1α gene and FTO gene were associated with having GDM and preeclampsia in Turkish women. Healthy pregnant women (n = 101) and women with GDM (n = 169) were included. GDM was divided into two groups as GDM-only (n = 90) and GDM-preeclampsia (n = 79). Genotyping of HNF1α gene p.I27L, p.A98V, and p.S487N, and FTO gene rs9939609 SNPs were performed using RT-PCR. The frequency of p.S487N, p.A98V, and FTO genotype were similar between the groups (p > .05). p.I27L GG-wild, GT, and TT genotype were 56.5%, 36.6%, and 6.9% in controls; 40.0%, 51.1%, and 8.9% in GDM-only; and 26.6%, 51.9%, and 21.5% in GDM-preeclampsia (p = .034). TT and GT genotype was more frequent in GDM-preeclampsia than in controls (p < .05). GT genotype was increased in GDM-only compared with controls (p < .05). TT genotype was more frequent in GDM-preeclampsia than in GDM-only (p < .05). p.I27L TT genotype was independently associated with increased blood pressure (BP) and urinary protein. p.I27L TT genotype was associated with increased preeclampsia risk in patients with GDM by increasing BP and urinary protein.


Feasibility of a novel mHealth management system to capture and improve medication adherence among adolescents with asthma.
Currently, 7.1 million children in the United States have asthma. Nonadherence to daily controller asthma medication is common, leading to more severe symptoms, overuse of rescue medication, and increased hospitalizations. The purpose of this study was to develop and evaluate the feasibility and acceptability of a novel mHealth management system composed of a sensored device, which is connected to mobile phone app that is designed to monitor and improve asthma medication adherence. The asthma management system was designed using well-established behavioral theory. Seven adolescents aged 11-18 years were enrolled and given an adherence sensor, and four of those also received a mobile phone app with game features and reminders. Five patients completed the study, and one was lost to follow-up in each group. Mobile app users and their parents participated in focus groups to assess patient preferences. Feasibility was assessed by the ability of sensors to capture real-time medication data. Acceptability was assessed by patient questionnaire and focus group analysis. Successful upload of real-time data from six of seven inhaler sensors to the HIPAA-compliant server demonstrates the feasibility of at-home patient monitoring using the sensor device. All three mobile app users who completed the study reported interest in continued use of the management system and would recommend the app to friends. Unstructured interviews and focus groups revealed that patients felt that the intervention helped their sense of asthma control. This study demonstrates the feasibility of using the sensor device to remotely monitor real-time medication usage, and user feedback demonstrates the acceptability of the intervention for patient use. The findings provide guidance for the improvement of study design and technology development. Further research is needed to assess the efficacy of the intervention.


Fast Spiking of a Mott VO2-Carbon Nanotube Composite Device.
The recent surge of interest in brain-inspired computing and power-efficient electronics has dramatically bolstered development of computation and communication using neuron-like spiking signals. Devices that can produce rapid and energy-efficient spiking could significantly advance these applications. Here we demonstrate direct current or voltage-driven periodic spiking with sub-20 ns pulse widths from a single device composed of a thin VO2 film with a metallic carbon nanotube as a nanoscale heater, without using an external capacitor. Compared with VO2-only devices, adding the nanotube heater dramatically decreases the transient duration and pulse energy, and increases the spiking frequency, by up to 3 orders of magnitude. This is caused by heating and cooling of the VO2 across its insulator-metal transition being localized to a nanoscale conduction channel in an otherwise bulk medium. This result provides an important component of energy-efficient neuromorphic computing systems and a lithography-free technique for energy-scaling of electronic devices that operate via bulk mechanisms.


The impact of resource availability on bacterial resistance to phages in soil.
Resource availability can affect the coevolutionary dynamics between host and parasites, shaping communities and hence ecosystem function. A key finding from theoretical and in vitro studies is that host resistance evolves to greater levels with increased resources, but the relevance to natural communities is less clear. We took two complementary approaches to investigate the effect of resource availability on the evolution of bacterial resistance to phages in soil. First, we measured the resistance and infectivity of natural communities of soil bacteria and phage in the presence and absence of nutrient-providing plants. Second, we followed the real-time coevolution between defined bacteria and phage populations with resource availability manipulated by the addition or not of an artificial plant root exudate. Increased resource availability resulted in increases in bacterial resistance to phages, but without a concomitant increase in phage infectivity. These results suggest that phages may have a reduced impact on the control of bacterial densities and community composition in stable, high resource environments.


The impact of equilibrium assumptions on tests of selection.
With the increasing availability and quality of whole genome population data, various methodologies of population genetic inference are being utilized in order to identify and quantify recent population-level selective events. Though there has been a great proliferation of such methodology, the type-I and type-II error rates of many proposed statistics have not been well-described. Moreover, the performance of these statistics is often not evaluated for different biologically relevant scenarios (e.g., population size change, population structure), nor for the effect of differing data sizes (i.e., genomic vs. sub-genomic). The absence of the above information makes it difficult to evaluate newly available statistics relative to one another, and thus, difficult to choose the proper toolset for a given empirical analysis. Thus, we here describe and compare the performance of four widely used tests of selection: SweepFinder, SweeD, OmegaPlus, and iHS. In order to consider the above questions, we utilize simulated data spanning a variety of selection coefficients and beneficial mutation rates. We demonstrate that the LD-based OmegaPlus performs best in terms of power to reject the neutral model under both equilibrium and non-equilibrium conditions-an important result regarding the relative effectiveness of linkage disequilibrium relative to site frequency spectrum based statics. The results presented here ought to serve as a useful guide for future empirical studies, and provides a guide for statistical choice depending on the history of the population under consideration. Moreover, the parameter space investigated and the Type-I and Type-II error rates calculated, represent a natural benchmark by which future statistics may be assessed.


Cutting Edge: Influenza A virus activates TLR3-dependent inflammatory and RIG-I-dependent antiviral responses in human lung epithelial cells.
Influenza A virus (IAV) triggers a contagious acute respiratory disease that causes considerable mortality annually. Recently, we established a role for the pattern-recognition TLR3 in the response of lung epithelial cells to IAV-derived dsRNA. However, additional nucleic acid-recognition proteins have lately been implicated as key viral sensors, including the RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene (MDA)-5. In this study, we investigated the respective role of TLR3 vs RIG-I/MDA-5 signaling in human respiratory epithelial cells infected by IAV using BEAS-2B cells transfected with vectors encoding either a dominant-negative form of TLR3 or of mitochondrial antiviral signaling protein (MAVS; a signaling intermediate of RIG-I and MDA-5), or with plasmids overexpressing functional RIG-I or MDA-5. We demonstrate that the sensing of IAV by TLR3 primarily regulates a proinflammatory response, whereas RIG-I (but not MDA-5) mediates both a type I IFN-dependent antiviral signaling and a proinflammatory response.


Myogenesis of Siboglinum fiordicum sheds light on body regionalisation in beard worms (Siboglinidae, Annelida).
Many annelids, including well-studied species such as Platynereis, show similar structured segments along their body axis (homonomous segmentation). However, numerous annelid species diverge from this pattern and exhibit specialised segments or body regions (heteronomous segmentation). Recent phylogenomic studies and paleontological findings suggest that a heteronomous body architecture may represent an ancestral condition in Annelida. To better understand the segmentation within heteronomous species we describe the myogenesis and mesodermal delineation of segments in Siboglinum fiordicum during development. Employing confocal and transmission electron microscopy we show that the somatic longitudinal musculature consists of four separate strands, among which ventrolateral one is the most prominent and is proposed to drive the search movements of the head of the late metatrochophore. The somatic circular musculature lies inside the longitudinal musculature and is predominantly developed at the anterior end of the competent larva to support the burrowing behaviour. Our application of transmission electron microscopy allows us to describe the developmental order of the non-muscular septa. The first septum to form is supported by thick bundles of longitudinal muscles and separates the body into an anterior and a posterior region. The second group of septa to develop further divides the posterior body region (opisthosoma) and is supported by developing circular muscles. At the late larval stage, a septum reinforced by circular muscles divides the anterior body region into a forepart and a trunk segment. The remaining septa and their circular muscles form one by one at the very posterior end of the opisthosoma. The heteronomous Siboglinum lacks the strict anterior to posterior sequence of segment formation as it is found in the most studied annelid species. Instead, the first septum divides the body into two body regions before segments are laid down in first the posterior opisthosoma and then in the anterior body, respectively. Similar patterns of segment formation are described for the heteronomous chaetopterid Chaetopterus variopedatus and serpulid Hydroides elegans and may represent an adaptation of these annelids to the settlement and transition to the sedentarian-tubiculous mode of life.


Individual differences in the emotional modulation of gaze-cuing.
Gaze-cuing refers to the spontaneous orienting of attention towards a gazed-at location, characterised by shorter response times to gazed-at than non-gazed at targets. Previous research suggests that processing of these gaze cues interacts with the processing of facial expression cues to enhance gaze-cuing. However, whether only negative emotions (which signal potential threat or uncertainty) can enhance gaze-cuing is still debated, and whether this emotional modulation varies as a function of individual differences still remains largely unclear. Combining data from seven experiments, we investigated the emotional modulation of gaze-cuing in the general population as a function of participant sex, and self-reported subclinical trait anxiety, depression, and autistic traits. We found that (i) emotional enhancement of gaze-cuing can occur for both positive and negative expressions, (ii) the higher the score on the Attention to Detail subscale of the Autism Spectrum Quotient, the smaller the emotional enhancement of gaze-cuing, especially for happy expressions, and (iii) emotional modulation of gaze-cuing does not vary as a function of participant anxiety, depression or sex, although women display an overall larger gaze-cuing effect than men.


Anterior Cervical Corpectomy and Fusion and Anterior Cervical Discectomy and Fusion Using Titanium Mesh Cages for Treatment of Degenerative Cervical Pathologies: A Literature Review.
Anterior cervical corpectomy and fusion (ACCF) and anterior cervical discectomy and fusion (ACDF) are 2 effective and safe surgical treatments of degenerative cervical pathologies and are associated with a high percentage of excellent clinical outcomes when a graft or device must be used during the surgery, such as an allograft, autograft, nano-hydroxyapatite/polyamide cages, poly-ether-ether-ketone (PEEK) cages, and titanium mesh cages (TMCs). Although TMCs have been used in cervical surgeries for almost 2 decades, no specific reviews have been performed introducing the state of this material. Thus, in the present review, we discuss the status of using TMCs in anterior cervical surgeries. Studies that tested the usage of TMCs in treating degenerative cervical pathologies were included in this review. The development and progress of TMCs, the biomechanical analysis of TMCs, the radiological and clinical assessment of TMCs, the advantages and disadvantages of using TMCs, and their prospects for future applications as a device of ACCF and ACDF in treating degenerative cervical pathologies are discussed. Studies included in this review showed that TMCs can provide sufficient biomechanical stability. Furthermore, the TMCs used in anterior cervical fusion avoid the donor-site morbidity and achieve a solid bony fusion. However, there are some shortcomings. The structural characteristics and the design of TMCs cause the TMC subsidence rate to remain high, thus resulting in multiple related complications. We believe that due to the virtues of TMCs, they are worthy of application and promotion. However, the structure of TMCs should be further optimized to reduce the TMC subsidence rate and subsidence-related complications, ultimately achieving excellent clinical results.


Earliest signs of life on land preserved in ca. 3.5 Ga hot spring deposits.
The ca. 3.48 Ga Dresser Formation, Pilbara Craton, Western Australia, is well known for hosting some of Earth's earliest convincing evidence of life (stromatolites, fractionated sulfur/carbon isotopes, microfossils) within a dynamic, low-eruptive volcanic caldera affected by voluminous hydrothermal fluid circulation. However, missing from the caldera model were surface manifestations of the volcanic-hydrothermal system (hot springs, geysers) and their unequivocal link with life. Here we present new discoveries of hot spring deposits including geyserite, sinter terracettes and mineralized remnants of hot spring pools/vents, all of which preserve a suite of microbial biosignatures indicative of the earliest life on land. These include stromatolites, newly observed microbial palisade fabric and gas bubbles preserved in inferred mineralized, exopolymeric substance. These findings extend the known geological record of inhabited terrestrial hot springs on Earth by ∼3 billion years and offer an analogue in the search for potential fossil life in ancient Martian hot springs.


Pediatric inflammatory bowel disease.
The prevalence of early-onset inflammatory bowel disease has been on the rise, with children and adolescents currently accounting for approximately 30% of all patients with this condition. Remarkable new advances in diagnostic modalities and therapy for adults with inflammatory bowel disease, and further information about the role of genetics in determining susceptibility to disease make the review of the recent literature in pediatric inflammatory bowel disease more timely than ever. In the area of genetics, new studies provide strong evidence for genetic susceptibility to disease, and match genotype with phenotypic presentation. A few studies examine the use of noninvasive diagnostic modalities, such as MRI, and biomarkers (fecal lactoferrin) in pediatric inflammatory bowel disease. Remarkable new agents in therapy for adults with inflammatory bowel disease have been empirically administered to children with inflammatory bowel disease. The first attempts to systematically study the effects of these agents in children and adolescents are reviewed here. Furthermore, new studies revise our notion of surgical outcomes in pediatric inflammatory bowel disease. Although premature for clinical practice application, the role of genetic testing in determining disease susceptibility and assisting with prognosis and course of therapy is clearly evolving and needs further study. As new therapeutic agents join the available treatments of inflammatory bowel disease it is imperative to include pediatric patients in clinical trials. The goals of future studies will be to alter the natural history of early-onset inflammatory bowel disease, reduce the frequency of recurrences, and perhaps reduce requirements for surgical intervention.


Socioeconomic inequalities of Long COVID: a retrospective population-based cohort study in the United Kingdom.
To estimate the risk of Long COVID by socioeconomic deprivation and to further examine the inequality by sex and occupation. We conducted a retrospective population-based cohort study using data from the ONS COVID-19 Infection Survey between 26 April 2020 and 31 January 2022. This is the largest nationally representative survey of COVID-19 in the UK with longitudinal data on occupation, COVID-19 exposure and Long COVID. Community-based survey in the UK. A total of 201,799 participants aged 16 to 64 years and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The risk of Long COVID at least 4 weeks after SARS-CoV-2 infection by index of multiple deprivation (IMD) and the modifying effects of socioeconomic deprivation by sex and occupation. Nearly 10% (n = 19,315) of participants reported having Long COVID. Multivariable logistic regression models, adjusted for a range of variables (demographic, co-morbidity and time), showed that participants in the most deprived decile had a higher risk of Long COVID (11.4% vs. 8.2%; adjusted odds ratio (aOR): 1.46; 95% confidence interval (CI): 1.34, 1.59) compared to the least deprived decile. Significantly higher inequalities (most vs. least deprived decile) in Long COVID existed in healthcare and patient-facing roles (aOR: 1.76; 95% CI: 1.27, 2.44), in the education sector (aOR: 1.68; 95% CI: 1.31, 2.16) and in women (aOR: 1.56; 95% CI: 1.40, 1.73) than men (aOR: 1.32; 95% CI: 1.15, 1.51). This study provides insights into the heterogeneous degree of inequality in Long COVID by deprivation, sex and occupation. These findings will help inform public health policies and interventions in incorporating a social justice and health inequality lens.


In-gel nonspecific proteolysis for elucidating glycoproteins: a method for targeted protein-specific glycosylation analysis in complex protein mixtures.
Determining protein-specific glycosylation in protein mixtures remains a difficult task. A common approach is to use gel electrophoresis to isolate the protein followed by glycan release from the identified band. However, gel bands are often composed of several proteins. Hence, release of glycans from specific bands often yields products not from a single protein but a composite. As an alternative, we present an approach whereby glycans are released with peptide tags allowing verification of glycans bound to specific proteins. We term the process in-gel nonspecific proteolysis for elucidating glycoproteins (INPEG). INPEG combines rapid gel separation of a protein mixture with in-gel nonspecific proteolysis of protein bands followed by tandem mass spectrometry (MS) analysis of the resulting N- and O-glycopeptides. Here, in-gel digestion is shown for the first time with nonspecific and broad specific proteases such as Pronase, proteinase K, pepsin, papain, and subtilisin. Tandem MS analysis of the resulting glycopeptides separated on a porous graphitized carbon (PGC) chip was achieved via nanoflow liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (nano-LC/Q-TOF MS). In this study, rapid and automated glycopeptide assignment was achieved via an in-house software (Glycopeptide Finder) based on a combination of accurate mass measurement, tandem MS data, and predetermined protein identification (obtained via routine shotgun analysis). INPEG is here initially validated for O-glycosylation (κ casein) and N-glycosylation (ribonuclease B). Applications of INPEG were further demonstrated for the rapid determination of detailed site-specific glycosylation of lactoferrin and transferrin following gel separation and INPEG analysis on crude bovine milk and human serum, respectively.


Review of Sickle Cell Disease and Spinal Pathology.
Sickle cell disease (SCD) is a relatively common blood disorder that has profound implications on the musculoskeletal system and particularly the spine; however, there is a paucity of data in the literature discussing this important topic. (1) To elucidate common spinal pathologies affecting patients with SCD, as well as the medical and surgical treatments available for these patients. (2) To discuss indications for surgical management of spinal complications of SCD and important for orthopedic surgeons when taking patients with SCD to the operating room. A narrative review of the literature was performed. Patients with SCD have a significantly higher risk of developing spinal pathologies including vertebral osteomyelitis, compression fracture, vertebral vaso-occlusive crises, and osteoporosis, among others. In addition, patients with sickle cell disease are particularly susceptible to developing perioperative and post-operative complications including surgical site infection, implant malfunction, and vertebral body compression fracture. Postoperatively patients with SCD are prone to developing complications and adequate hydration is necessary in order to reduce complications of SCD. Several spinal pathologies may arise secondary to SCD and distinguishing these pathologies from one another may be challenging due to similarities in symptoms and inflammatory markers. Although most patients with SCD can benefit from conservative treatment involving rest, symptomatic therapy, antibiotic therapy, and/or orthosis, surgical intervention may be indicated in certain cases. It is preferable to avoid surgery in patients with SCD due to an increased risk of complications such as wound infection and vaso-occlusive crisis.


Characteristics Of Preterm With Sight Threatening Retinopathy Of Prematurity.
Retinopathy of prematurity (ROP) is a preventable and treatable vasoproliferative disorder of the retina which develops mostly in preterm babies. It is a leading cause of childhood blindness and more common in under developed countries. Prevalence of the severe ROP is 7.7% in Pakistan. We reviewed the characteristics of preterm babies with severe ROP to evaluate the predictors of sight threatening ROP. Our study was conducted at the NICU of Aga Khan University Hospital which is a tertiary care private sector hospital in Karachi. Ninety-seven cases of severe ROP were found out of which 83 cases were enrolled. Data on determinants for ROP were collected including gestational age, birth weight, weight gain at two and four weeks, h/o blood transfusion, supplementary oxygen, presence of PDA and its treatment. Data analysis was done by using SPSS version 20.0. Frequency of severe ROP in our cohort was 5.95%. Mean gestational age for severe ROP was 28.27±1.79 and mean birth weight was 1069.16±271.71 grams. The overall mean weight gain per week in these babies was 94.62±75.64 grams. Supplementary oxygen was provided in almost 100% (82/83 cases) of cases. Surfactant was given to 56.6 % babies. PDA was found in 23 cases out of which 19 were treated by medical therapy whereas surgical treatment was done in 4 cases. Severe Retinopathy of prematurity was directly correlated with low birth weight, and gestational age. An average, weight gain in four weeks was lower in ROP babies (94.62±75.64 grams) than the recommended weight gain (WHO recommended 140-210 gm per week). This could be associated with the development and severity of ROP requiring treatment. Therefore, a prospective case control study is required to further identify risk factors associated with the above cohort. Screening and follow up of all such babies according to the international criteria is the need of the day.


Slow growth of Burkholderia pseudomallei compared to other pathogens in an adapted blood culture system in Phnom Penh, Cambodia.
Burkholderia pseudomallei is a key pathogen causing bloodstream infections at Sihanouk Hospital Center of Hope, Phnom Penh, Cambodia. Here, visual instead of automated detection of growth of commercial blood culture bottles is done. The present study assessed the performance of this system. Blood culture sets, consisting of paired adult aerobic and anaerobic bottles (bioMérieux, FA FAN 259791 and FN FAN 252793) were incubated in a standard incubator for 7 days after reception. Each day, the bottle growth indicator was visually inspected for colour change indicating growth. Blind subculture was performed from the aerobic bottle at day 3. From 2010 to 2015, 11 671 sets representing 10 389 suspected bloodstream infection episodes were documented. In 1058 (10.2 %) episodes, pathogens grew; they comprised Escherichia coli (31.7 %), Salmonella Paratyphi A (13.9 %), B. pseudomallei (8.5 %), Staphylococcus aureus (7.8 %) and Klebsiella pneumoniae (7.0 %). Blind subculture yielded 72 (4.1 %) pathogens, mostly (55/72, 76.4 %) B. pseudomallei. Cumulative proportions of growth at day 2 were as follows: E. coli: 85.0 %, Salmonella Paratyphi A: 85.0 %, K. pneumoniae: 76.3 % and S. aureus: 52.2 %; for B. pseudomallei, this was only 4.0 %, which increased to 70.1 % (70/99) at day 4 mainly by detection on blind subculture (55/99). Compared to the anaerobic bottles, aerobic bottles had a higher yield and a shorter time-to-detection, particularly for B. pseudomallei. Visual inspection for growth of commercial blood culture bottles in a low-resource setting provided satisfactory yield and time-to-detection. However, B. pseudomallei grew slowly and was mainly detected by blind subculture. The aerobic bottle outperformed the anaerobic bottle.


Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis.
Blockade of small GTPase-RhoA signaling pathway is considered a candidate translational strategy to improve functional outcome after spinal cord injury (SCI) in humans. Pooling preclinical evidence by orthodox meta-analysis is confounded by missing data (publication bias). To conduct a systematic review and meta-analysis of RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) blocking approaches to (1) analyze the impact of bias that may lead to inflated effect sizes and (2) determine the normalized effect size of functional locomotor recovery after experimental thoracic SCI. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the effect of RhoA/ROCK inhibitors (C3-exoenzmye, fasudil, Y-27632, ibuprofen, siRhoA, and p21) in experimental spinal cord hemisection, contusion, or transection on locomotor recovery measured by the Basso, Beattie, and Bresnahan score or the Basso Mouse Scale for Locomotion. Two investigators independently assessed the identified studies. Details of individual study characteristics from each publication were extracted and effect sizes pooled using a random effects model. We assessed risk for bias using a 9-point-item quality checklist and calculated publication bias with Egger regression and the trim and fill method. A stratified meta-analysis was used to assess the impact of study characteristics on locomotor recovery. Thirty studies (725 animals) were identified. RhoA/ROCK inhibition was found to improve locomotor outcome by 21% (95% CI, 16.0-26.6). Assessment of publication bias by the trim and fill method suggested that 30% of experiments remain unpublished. Inclusion of these theoretical missing studies suggested a 27% overestimation of efficacy, reducing the overall efficacy to a 15% improvement in locomotor recovery. Low study quality was associated with larger estimates of neurobehavioral outcome. Taking into account publication bias, RhoA/ROCK inhibition improves functional outcome in experimental SCI by 15%. This is a plausible strategy for the pharmacological augmentation of neurorehabilitation after human SCI. These findings support the necessity of a systematic analysis to identify preclinical bias before embarking on a clinical trial.


Optical characterization of alcohol-infiltrated one-dimensional silicon photonic crystals.
In this work, experimental results on the optical characterization of alcohol-infiltrated silicon/air one-dimensional photonic crystals (1D-PhCs), fabricated by electrochemical micromachining of silicon, are presented. The spectral reflectivity of high-order hybrid 1D-PhCs with a spatial period of 8 microm was measured, in the wavelength range 1.0-1.7 microm, when alcohols (ethanol and isopropanol) substitute air inside the trenches. A reliable redshift is observed in the presence of alcohols, with respect to air, which allows one to discriminate the refractive index difference between the alcohols. Experimental data are in good agreement with numerical results calculated by using the characteristic matrix method, modified to take into account surface roughness of silicon walls.


Discrete cerebral hypothermia in the management of traumatic brain injury: a randomized controlled trial.
Hypothermia has been extensively evaluated in the management of traumatic brain injury (TBI), but no consensus as to its effectiveness has yet been reached. Explanatory hypotheses include a possible confounding effect of the neuroprotective benefits by adverse systemic effects. To minimize the systemic effects, the authors evaluated a selective cerebral cooling system, the CoolSystem Discrete Cerebral Hypothermia System (a "cooling cap"), in the management of TBI. A prospective randomized controlled clinical trial was conducted at Grady Memorial Hospital, a Level I trauma center. Adults admitted with severe TBI (Glasgow Coma Scale [GCS] score < or = 8) were eligible. Patients assigned to the treatment group received the cooling cap, while those in the control group did not. Patients in the treatment group were treated with selective cerebral hypothermia for 24 hours, then rewarmed over 24 hours. Their intracranial and bladder temperatures, cranial-bladder temperature gradient, Glasgow Outcome Scale (GOS) and Functional Independence Measure (FIM) scores, and mortality rates were evaluated. The primary outcome was to establish a cranial-bladder temperature gradient in those patients with the cooling cap. The secondary outcomes were mortality and morbidity per GOS and FIM scores. The cohort comprised 25 patients (12 in the treatment group, 13 controls). There was no significant intergroup difference in demographic data or median GCS score at enrollment (treatment group 3.0, controls 3.0; p = 0.7). After the third hour of the study, the mean intracranial temperature of the treatment group was significantly lower than that of the controls at all time points except Hours 4 (p = 0.08) and 6 (p = 0.08). However, the target intracranial temperature of 33 degrees C was achieved in only 2 patients in the treatment group. The mean intracranial-bladder temperature gradient was not significant for the treatment group (p = 0.07) or the controls (p = 0.67). Six (50.0%) of 12 patients in the treatment group and 4 (30.8%) of 13 in the control group died (p = 0.43). The medians of the maximum change in GOS and FIM scores during the study period (28 days) for both groups were 0. There was no significant difference in complications between the groups (p value range 0.20-1.0). The cooling cap was not effective in establishing a statistically significant cranial-bladder temperature gradient or in reaching the target intracranial temperature in the majority of patients. No significant difference was achieved in mortality or morbidity between the 2 groups. As the technology currently stands, the Discrete Cerebral Hypothermia System cooling cap is not beneficial for the management of TBI. Further refinement of the equipment available for the delivery of selective cranial cooling will be needed before any definite conclusions regarding the efficacy of discrete cerebral hypothermia can be reached.


Effects of Methyl Mercury Chloride on Rat Hippocampus Structure.
The objective of this study is to investigate the impacts of Methyl Mercury Chloride (MMC) on cognitive functions and ultrastructural changes of hippocampus in Sprague Dawley (SD) rats. Thirty healthy 20-day-old male SD rats weighing 30-40 g were randomly divided into three groups to receive daily injections. Two different dose levels were used: 4 mg/kg as high dose (H-MMC) and 2 mg/kg as low dose (L-MMC).The control group received 4 mg/kg saline solution (N-NaCl). After daily subcutaneous injection for 50 days, 6-day Morris water maze tests were used to assess the learning and memory functions of the rats. After a 5-day continuous training, spatial probe tests were conducted of times and paths crossing to the target quadrant on the 6th day. After the rats were euthanized, their hippocampus sections were stained with hematoxylin and eosin and analyzed under bothoptical microscope and electron microscope. The time H-MMC group spent in finding platform was significantly longer as compared toN-NaCl group on day 2 to day 5 and L-MMC group on day 4 to day 5. The number of crossing times of H-MMC group to the target quadrant was 0.63 ± 0.74, which is much lower than C-NaCl group (3.13 ± 1.56) with P value <0.05. No statistically significant difference in crossing times was found between L-MMC and C-NaCl groups. For H-MMC group, decreasing number of neurons and disorganized nerve cells were examined under light microscope. Swelling and dissolution of Golgi complex were examined under electron microscope, along with endoplasmic reticulum expansion and cytoplasmic edema. Mild cytoplasmic edema was found in L-MMC group. MMC can cause cognitive impairment in terms of learning and memory in SD rats. Additionally, it can also cause changes in the ultrastructure of neurons and morphological changes in the hippocampus, causing significant damage.


In vivo role of leukocyte ADAM17 in the inflammatory and host responses during E. coli-mediated peritonitis.
Inflammation is the body's initial response to infection, which is harmful when excessive, as exemplified in sepsis inflammatory syndromes. Ectodomain shedding by the membrane metalloprotease ADAM17 is an emerging regulator of inflammation, as it directs the activity of various inflammatory modulators. At this time, however, little is known about the in vivo function of ADAM17. Here, we show that ADAM17-deficient leukocytes afforded mice a survival benefit following Escherichia coli-mediated peritoneal sepsis, which was associated with a reduction in systemic proinflammatory cytokine levels and bacterial burden. A more rapid yet transitory neutrophil infiltration into the peritoneal cavity of conditional ADAM17 knockout mice was observed when compared with control mice, suggesting a mechanism for their enhanced clearance of bacteria. Preventing the shedding of L-selectin augments neutrophil recruitment, and we show that L-selectin shedding by peritoneal neutrophils in conditional ADAM17 knockout mice was impaired. Moreover, their peritoneal TNF-alpha levels were markedly lower than control mice following E. coli challenge. These events indicate key molecular processes involved in the altered time course of neutrophil recruitment in conditional ADAM17 knockout mice. Overall, our study provides novel in vivo evidence of the instrumental role of ADAM17 in modulating inflammation and host resistance during Gram-negative bacterial infection.


The Expressed MicroRNA-mRNA Interactions of Toxoplasma gondii.
MicroRNAs (miRNAs) are involved in post-transcriptional modulation of gene expression and thereby have a large influence on the resulting phenotype. We have previously shown that miRNAs may be involved in the communication between Toxoplasma gondii and its hosts and further confirmed a number of proposed specific miRNAs. Yet, little is known about the internal regulation via miRNAs in T. gondii. Therefore, we predicted pre-miRNAs directly from the type II ME49 genome and filtered them. For the confident hairpins, we predicted the location of the mature miRNAs and established their target genes. To add further confidence, we evaluated whether the hairpins and their targets were co-expressed. Such co-expressed miRNA and target pairs define a functional interaction. We extracted all such functional interactions and analyzed their differential expression among strains of all three clonal lineages (RH, PLK, and CTG) and between the two stages present in the intermediate host (tachyzoites and bradyzoites). Overall, we found ~65,000 expressed interactions of which ~5,500 are differentially expressed among strains but none are significantly differentially expressed between developmental stages. Since miRNAs and target decoys can be used as therapeutics we believe that the list of interactions we provide will lead to novel approaches in the treatment of toxoplasmosis.


Income-based disparities in health care utilisation under universal health coverage in Brazil, 2002-2003.
Since Brazil's adoption of universal health care in 1988, the country's health care system has consisted of a mix of private providers and free public providers. We test whether income-based disparities in medical visits and medications remain in Brazil despite universal coverage using a nationally representative sample of over 48,000 households. Additional income is associated with less public sector utilisation and more private sector utilisation, both using simple correlations and regressions controlling for household characteristics and local area fixed effects. Importantly, the increase in private care use is greater than the drop in public care use. Also, income and unmet medical needs are negatively associated. These results suggest that access limitations remain for low-income households despite the availability of free public care.


A Versatile and Scalable Strategy to Discrete Oligomers.
A versatile strategy is reported for the multigram synthesis of discrete oligomers from commercially available monomer families, e.g., acrylates, styrenics, and siloxanes. Central to this strategy is the identification of reproducible procedures for the separation of oligomer mixtures using automated flash chromatography systems with the effectiveness of this approach demonstrated through the multigram preparation of discrete oligomer libraries (Đ = 1.0). Synthetic availability, coupled with accurate structural control, allows these functional building blocks to be harnessed for both fundamental studies as well as targeted technological applications.


Learning RuBisCO's birth and subsequent environmental adaptation.
It is believed that organisms that first appeared after the formation of the earth lived in a very limited environment, making full use of the limited number of genes. From these early organisms' genes, more were created by replication, mutation, recombination, translocation, and transmission of other organisms' DNA; thus, it became possible for ancient organisms to grow in various environments. The photosynthetic CO2-fixing enzyme RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) began to function in primitive methanogenic archaea and has been evolved as a central CO2-fixing enzyme in response to the large changes in CO2 and O2 concentrations that occurred in the subsequent 4 billion years. In this review, the processes of its adaptation to be specialized for CO2 fixation will be presented from the viewpoint of functions and structures of RuBisCO.


Hydroxytyrosol promotes autophagy by regulating SIRT1 against advanced oxidation protein product‑induced NADPH oxidase and inflammatory response.
Advanced oxidation protein products (AOPPs) can trigger NADPH oxidase (NOX) and lead to the production of reactive oxygen species (ROS) in the pathophysiology of rheumatoid arthritis (RA). Hydroxytyrosol (HT) is a phenolic composite in olive oil that has antioxidant and anti‑inflammatory effects and enhances autophagy. Early research has revealed that HT can activate the silent information regulator 1 (SIRT1) pathway to induce autophagy and alleviate the cartilage inflammatory response caused by H2O2. However, whether HT can attenuate AOPP‑induced NOX and inflammatory responses remains to be elucidated. The present study aimed to investigate how HT can alleviate the damage caused by AOPPs. In cell experiments, chondrocytes were pre‑stimulated with HT and then exposed to AOPPs. First, it was found that HT promoted autophagy through the SIRT1 pathway, increased the expression of autophagy‑related proteins including microtubule‑associated protein 1 light chain 3, autophagy related (ATG)5 and ATG7, and decreased the expression of P62. Furthermore, HT reduced the expression of NOX, which was affected by AOPPs in chondrocytes through the SIRT1 pathway. Finally, the expression of inflammatory cytokines caused by AOPPs was downregulated following HT treatment. In conclusion, it was found that HT reduced the expression of NOX and inhibited the inflammatory response caused by AOPPs in chondrocytes through the SIRT1 pathway.


The effect of oxybutynin treatment on cognition in children with diurnal incontinence.
Oxybutynin is a powerful anticholinergic drug already known to impair cognition in the elderly. The impact of this drug on cognitive functioning in the pediatric population is unknown. We report the results of a study designed to assess the effect of oxybutynin on cognitive function in children. A total of 25 patients presenting with the primary symptom of daytime enuresis were recruited for this nonrandomized trial. All subjects initially received 4 weeks of behavior modification, followed by an additional 4 weeks of behavior modification either alone or with oxybutynin for continued treatment of enuresis. Neuropsychological testing was performed at baseline (4 weeks) and after additional therapy (8 weeks). Patient demographics included a male-to-female ratio of 11:14 and a mean age of 7.2 +/- 1.8 years. A total of 10 patients were assigned to the control group receiving behavior modification, and 15 patients were assigned to the treatment group receiving behavior modification plus oxybutynin. The oxybutynin treated patients had a lower overall performance at baseline pretreatment testing. However, performance in this group improved following treatment with oxybutynin. Oxybutynin, a commonly used pharmacological agent in pediatric urology, was not associated with cognitive impairment following treatment. However, we observed lower baseline cognitive functioning in patients whose parents chose oxybutynin over behavior modification alone. This finding may represent a selection bias. However, it also supports the need for a multidisciplinary approach to the treatment of patients with dysfunctional voiding, as some may have cognitive difficulties that have not previously been explored.


Task-Aware Sampling Layer for Point-Wise Analysis.
Sampling, grouping, and aggregation are three important components in the multi-scale analysis of point clouds. In this paper, we present a novel data-driven sampler learning strategy for point-wise analysis tasks. Unlike the widely used sampling technique, Farthest Point Sampling (FPS), we propose to learn sampling and downstream applications jointly. Our key insight is that uniform sampling methods like FPS are not always optimal for different tasks: sampling more points around boundary areas can make the point-wise classification easier for segmentation. Towards this end, we propose a novel sampler learning strategy that learns sampling point displacement supervised by task-related ground truth information and can be trained jointly with the underlying tasks. We further demonstrate our methods in various point-wise analysis tasks, including semantic part segmentation, point cloud completion, and keypoint detection. Our experiments show that jointly learning of the sampler and task brings better performance than using FPS in various point-based networks.


Frequency-dependent advantages of plasmid carriage by Pseudomonas in homogeneous and spatially structured environments.
The conditions promoting the persistence of a plasmid carrying a trait that may be mutually beneficial to other cells in its vicinity were studied in structured and unstructured environments. A large plasmid encoding mercury resistance in Pseudomonas fluorescens was used, and the mercury concentration allowing invasion from rare for both plasmid-bearing and plasmid-free cells was determined for different initial inoculum densities in batch-culture structured (filter surface) and unstructured (mixed broth) environments. A range of mercury concentrations were found where both cell types could coexist, the regions being relatively similar in the two types of environment although density-dependent in the unstructured environment. The coexistence is explained in terms of frequency-dependent selection of the mutually beneficial mercury resistance trait, and the dynamics of bacterial growth under batch culture conditions. However, the region of coexistence was complicated by conjugation which increased plasmid spread in the mixed broth culture but not the structured environment.


Design of improved membrane protein production experiments: quantitation of the host response.
Eukaryotic membrane proteins cannot be produced in a reliable manner for structural analysis. Consequently, researchers still rely on trial-and-error approaches, which most often yield insufficient amounts. This means that membrane protein production is recognized by biologists as the primary bottleneck in contemporary structural genomics programs. Here, we describe a study to examine the reasons for successes and failures in recombinant membrane protein production in yeast, at the level of the host cell, by systematically quantifying cultures in high-performance bioreactors under tightly-defined growth regimes. Our data show that the most rapid growth conditions of those chosen are not the optimal production conditions. Furthermore, the growth phase at which the cells are harvested is critical: We show that it is crucial to grow cells under tightly-controlled conditions and to harvest them prior to glucose exhaustion, just before the diauxic shift. The differences in membrane protein yields that we observe under different culture conditions are not reflected in corresponding changes in mRNA levels of FPS1, but rather can be related to the differential expression of genes involved in membrane protein secretion and yeast cellular physiology.


Predictors and Extent of Institutional Trust in Government, Banks, the Media and Religious Organisations: Evidence from Cross-Sectional Surveys in Six Asia-Pacific Countries.
Building or maintaining institutional trust is of central importance in democratic societies since negative experiences (potentially leading to mistrust) with government or other institutions may have a much more profound effect than positive experiences (potentially maintaining trust). Healthy democracy relies on more than simply trusting the national government of the time, and is mediated through other symbols of institutional power, such as the legal system, banks, the media and religious organisations. This paper focuses on institutional trust-the level and predictors of trust in some of the major institutions in society, namely politics, the media, banks, the legal system and religious organisations. We present analyses from a consolidated dataset containing data from six countries in the Asia Pacific region-Australia, Hong Kong, Japan, South Korea, Taiwan and Thailand. Cross-sectional surveys were undertaken in each country in 2009-10, with an overall sample of 6331. Analyses of differences in overall levels of institutional trust between countries were undertaken using Chi square analyses. Multivariate binomial logistic regression analysis was undertaken to identify socio-demographic predictors of trust in each country. Religious institutions, banks and the judicial system had the highest overall trust across all countries (70%, 70% and 67% respectively), followed by newspapers and TV (59% and 58%) and then political leaders (43%). The range of levels of higher trust between countries differed from 43% for banks (range 49% in Australia to 92% in Thailand) to 59% for newspapers (28% in Australia to 87% in Japan). Across all countries, except for Australia, trust in political leaders had the lowest scores, particularly in Japan and South Korea (25% in both countries). In Thailand, people expressed the most trust in religious organisations (94%), banks (92%) and in their judicial/legal system (89%). In Hong Kong, people expressed the highest level of trust in their judicial/legal system (89%), followed by religious organisations (75%) and banks (77%). Australian respondents reported the least amount of trust in TV/media (24%) and press/newspapers (28%). South Korea put the least trust in their political leaders (25%), their legal system (43%) and religious organisations (45%). The key predictors of lower trust in institutions across all countries were males, people under 44 years and people unsatisfied with the health and standard of living. We interpreted our data using Fukuyama's theory of 'high/low trust' societies. The levels of institutional trust in each society did not conform to our hypothesis, with Thailand exhibiting the highest trust (predicted to be medium level), Hong Kong and Japan exhibiting medium trust (predicted to be low and high respectively) and Australia and South Korea exhibiting low trust (predicted to be high and medium respectively). Taiwan was the only country where the actual and predicted trust was the same, namely low trust. Given the fact that these predictors crossed national boundaries and institutional types, further research and policy should focus specifically on improving trust within these groups in order that they can be empowered to play a more central role in democratic vitality.


Factors associated with not using folic acid supplements preconceptionally.
Neural tube defects are among the most common birth defects worldwide. Folic acid intake from one month before to three months after conception reduces the likelihood of neural tube defects by at least 50%. Since 1995, several campaigns have been organised in the Netherlands which resulted in 51% of pregnant women using folic acid supplements during the entire recommended period in the northern part of the Netherlands in 2005. Our research question was to gain insight into the current prevalence and factors associated with inadequate pregnancy-related use of folic acid supplements. Data from the DELIVER study were used, which is a population-based cohort study. Twenty midwifery practices across the Netherlands in 2009 and 2010. In total 5975 pregnant women completed a questionnaire covering items on sociodemographic and lifestyle factors, including folic acid intake. Of our study population, 55·5% (3318/5975) used folic acid supplements before conception. Several sociodemographic and lifestyle factors were associated with no preconception use of folic acid, of which non-Western ethnicity and not having a partner had the largest effect size. In the Netherlands, the folic acid intake before conception is suboptimal and has not improved over recent years. Fortification of staple foods with folic acid should be reconsidered as it would provide a more effective means of ensuring an adequate intake, especially for those groups of women who are unlikely to plan their pregnancies or to receive or respond to health promotion messages.


Homecare Robotic Systems for Healthcare 4.0: Visions and Enabling Technologies.
Powered by the technologies that have originated from manufacturing, the fourth revolution of healthcare technologies is happening (Healthcare 4.0). As an example of such revolution, new generation homecare robotic systems (HRS) based on the cyber-physical systems (CPS) with higher speed and more intelligent execution are emerging. In this article, the new visions and features of the CPS-based HRS are proposed. The latest progress in related enabling technologies is reviewed, including artificial intelligence, sensing fundamentals, materials and machines, cloud computing and communication, as well as motion capture and mapping. Finally, the future perspectives of the CPS-based HRS and the technical challenges faced in each technical area are discussed.


ACOG Committee Opinion No. 434: induced abortion and breast cancer risk.
The Relationship between induced abortion and the subsequent development of breast cancer has been the subject of a substantial amount of epidemiologic study. Early studies of the relationship between prior induced abortion and breast cancer risk were methodologically flawed. More rigorous recent studies demonstrate no causal relationship between induced abortion and a subsequent increase in breast cancer risk.


Bacterial Blight on Arugula, a New Disease Caused by Pseudomonas syringae pv. Alisalensis in California.
Beginning in 1995, a leaf spot disease has occasionally developed on the leafy crucifer arugula (Eruca vesicaria subsp. sativa) that is grown in coastal California as a fresh market commodity used mostly in bagged salad mixes. Initially, symptoms consist of small (<2 mm in diameter), angular, water-soaked spots that are visible from both sides of the leaf. The spots later enlarge, remain angular in shape, and turn brown to tan. A purple margin sometimes occurs around the spots. An important diagnostic feature is that this disease closely resembles downy mildew infections that have not produced sporangia (3). A blue-green fluorescent pseudomonad was consistently isolated from both types of lesions on King's medium B. Strains were levan positive, oxidase negative, and arginine dihydrolase negative. Strains did not rot potato slices but induced a hypersensitive reaction on tobacco (Nicotiana tabacum L. cv. Turk). These data indicated that the bacteria belonged to Lelliot's LOPAT group 1 (4). This was confirmed with data from fatty acid methyl ester analysis (MIS-TSBA version 4.10; MIDI, Inc., Newark, DE), which indicated that the strains were highly similar (similarity > = 0.758) to Pseudomonas syringae. Amplification of repetitive bacterial sequence-based polymerase chain reaction (rep-PCR) was used to determine the relationship between the P. syringae strains isolated from arugula and two common crucifer pathogens, P. syringae pv. maculicola and P. syringae pv. alisalensis (1). Using the BOXA1R primer, banding patterns for the arugula strains and the P. syringae pv. alisalensis pathotype were similar, differing by only one band. In contrast, the banding patterns of the arugula strains differed significantly from those of P. syringae pv. maculicola. Additionally, the arugula isolates were sensitive to a bacteriophage originally isolated for its ability to lyse P. syringae pv. alisalensis (1). Previously, the pathogen from arugula was reported to be P. syringae pv. maculicola (2). It is the intent of this disease note to clarify this identification. We completed Koch's postulates by confirming pathogenicity on arugula (cv. Rocket Salad). The strains were grown as nutrient broth shake cultures for 48 h at 24°C, adjusted to 108 CFU/ml, and misted onto 2- to 3-week old plants. Control plants were misted with sterile nutrient broth. After 4 to 5 days in a greenhouse (24 to 26°C), large, angular leaf lesions developed on all inoculated arugula plants. Strains were reisolated from symptomatic tissue and identified as P. syringae pv. alisalensis. Control plants remained symptomless. Similar methods confirmed that the host range of the arugula isolates were identical to that of P. syringae pv. alisalensis. The arugula and P. syringae pv. alisalensis isolates caused disease on broccoli (Brassica oleracea var. botrytis cvs. Patriot and Titleist), broccoli raab (B. rapa subsp. rapa cv. Sorento), and oats (Avena sativa cv. Montezuma), while P. syringae pv. maculicola caused disease on broccoli only. Pathogenicity tests were conducted two times with identical results. This confirms that the bacterial blight that has been occurring on commercial plantings of arugula is caused by P. syringae pv. alisalensis. References: (1) N. A. Cintas et al.Plant Dis. 86:992, 2002. (2) S. T. Koike et al. Plant Dis. 80:464, 1996. (3) S. T. Koike. Plant Dis. 82:1063, 1998. (4) R. A. Lelliott, J. Appl. Bacteriol. 29:470, 1966.


Transcriptome-wide comparison of the impact of Atoh1 and miR-183 family on pluripotent stem cells and multipotent otic progenitor cells.
Over 5% of the global population suffers from disabling hearing loss caused by multiple factors including aging, noise exposure, genetic predisposition, or use of ototoxic drugs. Sensorineural hearing loss is often caused by the loss of sensory hair cells (HCs) of the inner ear. A barrier to hearing restoration after HC loss is the limited ability of mammalian auditory HCs to spontaneously regenerate. Understanding the molecular mechanisms orchestrating HC development is expected to facilitate cell replacement therapies. Multiple events are known to be essential for proper HC development including the expression of Atoh1 transcription factor and the miR-183 family. We have developed a series of vectors expressing the miR-183 family and/or Atoh1 that was used to transfect two different developmental cell models: pluripotent mouse embryonic stem cells (mESCs) and immortalized multipotent otic progenitor (iMOP) cells representing an advanced developmental stage. Transcriptome profiling of transfected cells show that the impact of Atoh1 is contextually dependent with more HC-specific effects on iMOP cells. miR-183 family expression in combination with Atoh1 not only appears to fine tune gene expression in favor of HC fate, but is also required for the expression of some HC-specific genes. Overall, the work provides novel insight into the combined role of Atoh1 and the miR-183 family during HC development that may ultimately inform strategies to promote HC regeneration or maintenance.


Fine mapping of the chromosome 5B region carrying closely linked rust resistance genes Yr47 and Lr52 in wheat.
Fine mapping of Yr47 and Lr52 in chromosome arm 5BS of wheat identified close linkage of the marker sun180 to both genes and its robustness for marker-assisted selection was demonstrated. The widely effective and genetically linked rust resistance genes Yr47 and Lr52 have previously been mapped in the short arm of chromosome 5B in two F3 populations (Aus28183/Aus27229 and Aus28187/Aus27229). The Aus28183/Aus27229 F3 population was advanced to generate an F6 recombinant inbred line (RIL) population to identify markers closely linked with Yr47 and Lr52. Diverse genomic resources including flow-sorted chromosome survey sequence contigs representing the orthologous region in Brachypodium distachyon, the physical map of chromosome arm 5BS, expressed sequence tags (ESTs) located in the 5BS6-0.81-1.00 deletion bin and resistance gene analog contigs of chromosome arm 5BS were used to develop markers to saturate the target region. Selective genotyping was also performed using the iSelect 90 K Infinium wheat SNP assay. A set of SSR, STS, gene-based and SNP markers were developed and genotyped on the Aus28183/Aus27229 RIL population. Yr47 and Lr52 are genetically distinct genes that mapped 0.4 cM apart in the RIL population. The SSR marker sun180 co-segregated with Lr52 and mapped 0.4 cM distal to Yr47. In a high resolution mapping population of 600 F2 genotypes Yr47 and Lr52 mapped 0.2 cM apart and marker sun180 was placed 0.4 cM distal to Lr52. The amplification of a different sun180 amplicon (195 bp) than that linked with Yr47 and Lr52 (200 bp) in 204 diverse wheat genotypes demonstrated its robustness for marker-assisted selection of these genes.


Brainstem arteriovenous malformations: anatomical subtypes, assessment of "occlusion in situ" technique, and microsurgical results.
The surgical management of brainstem arteriovenous malformations (AVMs) might benefit from the definition of anatomical subtypes and refinements of resection techniques. Many brainstem AVMs sit extrinsically on pia mater rather than intrinsically in the parenchyma, allowing treatment by occluding feeding arteries circumferentially, interrupting draining veins after arteriovenous shunting is eliminated, and leaving the obliterated nidus behind. The authors report here the largest series of brainstem AVMs to define 6 subtypes, assess this "occlusion in situ" technique, and analyze the microsurgical results. Brainstem AVMs were categorized as 1 of 6 types: anterior midbrain, posterior midbrain, anterior pontine, lateral pontine, anterior medullary, and lateral medullary AVMs. Data from a prospectively maintained AVM registry were reviewed to evaluate multidisciplinary treatment results. During a 15-year period, the authors treated 29 patients with brainstem AVMs located in the midbrain (1 anterior and 6 posterior), pons (6 anterior and 7 lateral), and medulla (1 anterior and 8 lateral). The nidus was pial in 26 cases and parenchymal in 3 cases. Twenty-three patients (79%) presented with hemorrhage. Brainstem AVMs were either resected (18 patients, 62%) or occluded in situ (11 patients, 38%). All lateral pontine AVMs were resected, and the occlusion in situ rate was highest with anterior pontine AVMs (83%). Angiography confirmed complete obliteration in 26 patients (89.6%). The surgical mortality rate was 6.9%, and the rate of permanent neurological deterioration was 13.8%. At follow-up (mean 1.3 years), good outcomes (modified Rankin Scale [mRS] score ≤ 2) were observed in 18 patients (66.7%) and poor outcomes (mRS score of 3-5) were observed in 9 patients (33.3%). The mRS scores in 21 patients (77.8%) were unchanged or improved. The best outcomes were observed with lateral pontine (100%) and lateral medullary (75%) AVMs, and the rate of worsening/death was greatest with posterior midbrain and anterior pontine AVMs (50% each). Brainstem AVMs can be differentiated by their location in the brainstem (midbrain, pons, or medulla) and the surface on which they are based (anterior, posterior, or lateral). Anatomical subtypes can help the neurosurgeon determine how to advise patients, with lateral subtypes being a favorable surgical indication along with extrinsic pial location and hemorrhagic presentation. Most AVMs are dissected with the intention to resect them, and occlusion in situ is reserved for those AVMs that do not separate cleanly from the brainstem, that penetrate into the parenchyma, or are more anterior in location, where it is difficult to visualize and preserve perforating arteries (anterior pontine and lateral medullary AVMs). Although surgical morbidity is considerable, surgery results in a better obliteration rate than nonoperative management and is indicated in highly selected patients with high rerupture risks.


215 mandible fractures in 120 children: demographics, treatment, outcomes, and early growth data.
Optimal management of pediatric mandible fractures demands that the practitioner balance reduction and fixation with preservation of growth potential and function. The ideal synthesis of these goals has not yet been defined. The authors catalogue their experience with pediatric mandible fractures at a major pediatric teaching hospital with reference to demographics, injury type, treatment, and outcomes to inform future management of these injuries. Demographics, management, and outcomes of pediatric mandible fractures presenting over 10 years at a pediatric trauma center were assessed. Cephalometric analysis was conducted. Relationships among demographics, fracture type, management, outcomes, and growth were explored. Two hundred fifteen mandible fractures in 120 patients younger than 18 years were analyzed (average follow-up, 19.5 months). The condylar head and neck were fractured most frequently. Operative management was significantly more likely for children older than 12 years (p<0.05). Operative management and multiple fractures were significantly associated with a higher rate of adverse outcomes (p<0.05), but no adverse outcomes were considered to significantly affect mandibular function by patient or surgeon. No significant growth differences existed on cephalometric analysis between our cohort and age- and sex-matched controls (p>0.05). This study reports the demographics, treatment, and early follow-up of a sizable cohort of pediatric mandible fractures. Management principles for these injuries are outlined. Although definitive recommendations must be withheld until longer follow-up is available, the data presented here show that the treatment protocols used at the authors' center have yielded largely uncompromised mandibular function and growth thus far.


Clinical PET imaging of insulinoma and beta-cell hyperplasia.
Persistent hyperinsulinemic hypoglycemia (PHH) is caused by solitary benign insulinoma or hyperplasia of pancreatic beta cells. In infants, PHH is caused by functionally defective hyperplastic beta cells, which are either diffusely or focally distributed in the pancreas. In adults, insulinoma is the most common cause of PHH, but recently, an increasing number of beta-cell hyperplasias has been reported among adults. The cause of adult beta-cell hyperplasia is not known. Whether the increased use of bariatric surgery in the treatment of severe obesity plays a role here is under investigation. Accurate localization of disease focus in both insulinoma and focal beta-cell hyperplasia provides an important support for surgery, especially as the use of laparoscopic surgery has increased. Conventional imaging of these challenging pancreatic lesions has evolved during recent years, but current imaging methods still lack sufficient sensitivity or are invasive. In most pancreatic NETs, the usefulness of positron emission tomography (PET) with fluorine-labeled fluorodeoxyglucose ([(18)F]FDG) for lesion detection is limited because of the low glucose turnover of these tumors. Based on the capacity of pancreatic beta cells to take up and decarboxylate amine precursors, several investigators have studied patients with pancreatic NETs using aminoacid precursors, such as [(18)F]dihydroxyphenylalanine (DOPA) and [(11)C]hydroxytryptophan (5-HTP), in an attempt to increase the sensitivity of PET scanning. Another characteristic of NETs is the expression of somatostatin receptors, and thus encouraging studies with somatostatin receptor imaging with [(18)Ga]-labeled somatostatin analogs have emerged as a new interesting imaging tool for the diagnosis of pancreatic NETs. This article provides an overview of our experiences and the current literature on PET imaging in patients with PHH caused by insulinoma or beta-cell hyperplasia.


Communication with the seriously ill: physicians' attitudes in Saudi Arabia.
To study some ethical problems created by accession of a previously nomadic and traditional society to modern invasive medicine, by assessment of physicians' attitudes towards sharing information and decision-making with patients in the setting of a serious illness. Self-completion questionnaire administered in 1993. Riyadh, Jeddah, and Buraidah, three of the largest cities in Saudi Arabia. Senior and junior physicians from departments of internal medicine and critical care in six hospitals in the above cities. A total of 249 physicians participated in the study. Less than half (47%) indicated they provided information on diagnosis and prognosis of serious illnesses all the time. Physicians who were more senior and those who spoke Arabic fared better than other groups. The majority (75%) preferred to discuss information with close relatives rather than patients, even when the patients were mentally competent. Most of the physicians (72%) felt patients had the right to refuse a specific treatment modality, and 68% denied patients the right to demand such a treatment if considered futile. Further analysis showed that physicians' attitudes varied along a spectrum from passive (25%) to paternalistic (21%) with the largest group (47%) in a balanced position. In traditional societies where physicians are regarded as figures of authority and family ties are important, there is a considerable shift of access to information and decision-making from patients to their physicians and relatives in a manner that threatens patients' autonomy. Ethical principles, wider availability of invasive medical technology and a rise in public awareness dictate an attitude change.


Effect of electrical double layer on electric conductivity and pressure drop in a pressure-driven microchannel flow.
The effect of an electrical double layer (EDL) on microchannel flow has been studied widely, and a constant bulk electric conductivity is often used in calculations of flow rate or pressure drop. In our experimental study of pressure-driven micropipette flows, the pipette diameter is on the same order of magnitude as the Debye length. The overlapping EDL resulted in a much higher electric conductivity, lower streaming potential, and lower electroviscous effect. To elucidate the effect of overlapping EDL, this paper developed a simple model for water flow without salts or dissolved gases (such as CO(2)) inside a two-dimensional microchannel. The governing equations for the flow, the Poisson, and Nernst equations for the electric potential and ion concentrations and the charge continuity equation were solved. The effects of overlapping EDL on the electric conductivity, velocity distribution, and overall pressure drop in the microchannel were quantified. The results showed that the average electric conductivity of electrolyte inside the channel increased significantly as the EDL overlaps. With the modified mean electric conductivity, the pressure drop for the pressure-driven flow was smaller than that without the influence of the EDL on conductivity. The results of this study provide a physical explanation for the observed decrease in electroviscous effect for microchannels when the EDL layers from opposing walls overlap.


Assessment of Microbial Community Dynamics in River Bank Filtrate Using High-Throughput Sequencing and Flow Cytometry.
Surface-groundwater interactions play an important role in microbial community compositions of river bank filtrates. Surface water contaminations deriving from environmental influences are attenuated by biogeochemical processes in the hyporheic zone, which are essential for providing clean and high-quality drinking water in abstraction wells. Characterizing the flow regime of surface water into the groundwater body can provide substantial information on water quality, but complex hydraulic dynamics make predictions difficult. Thus, a bottom up approach using microbial community shifting patterns as an overall outcome of dynamic water characteristics could provide more detailed information on the influences that affect groundwater quality. The combination of high-throughput sequencing data together with flow cytometric measurements of total cell counts reveals absolute abundances among taxa, thus enhancing interpretation of bacterial dynamics. 16S rRNA high-throughput sequencing of 55 samples among six wells in a well field in Austria that is influenced by river bank filtrate within a time period of 3 months has revealed both, clear differences as well as strong similarity in microbiome compositions between wells and dates. A significant community shift from April to May occurred in four of six wells, suggesting that surface water flow regimes do affect these wells stronger than others. Triplicate sampling and subsequent sequencing of wells at different dates proved the method to be reproducible. Flow cytometric measurements of total cells indicate microbial shifts due to increased cell counts and emphasize the rise of allochthonous microorganisms. Typical freshwater bacterial lineages (Verrucomicrobia, Bacteroidetes, Actinobacteria, Cyanobacteria, Armatimonadetes) were identified as most increasing phyla during community shifts. The changes are most likely a result of increased water abstraction in the wells together with constant river water levels rather than rain events. The results provide important knowledge for future implementations of well utilization in dependency of the nearby Danube River water levels and can help drawing conclusions about the influence of surface water in the groundwater such that hygienically save and clean drinking water with a stable microbial community can be provided.


Predictors of colonic pathologies in active acromegaly: single tertiary center experience.
Regarding the incidence of colorectal malignancy and polyps in patients with acromegaly, studies reported different results in different populations. For this reason, the aim of this study was to determine the frequency of possible colonic pathologies, such as diverticula, polyps, and malignancies in Turkish patients with active acromegaly and factors affecting them. A total of 134 patients with acromegaly and 134 patients with irritable bowel syndrome/dyspeptic symptoms as a control group were included in the study. None of these patients had a previous or family history of colonic neoplasms. Colonoscopies of patients with acromegaly were performed before definitive surgery in a single center by experienced endoscopists. The acromegaly and control groups were similar in terms of age and sex. The incidence of all colonic polyps was significantly higher in the acromegaly group (p = 0.012). The frequency of hyperplastic polyps was also increased in the acromegaly group (p = 0.004); however, the frequencies of adenomatous polyps and colonic diverticula were similar in both groups. In the comparison of patients with acromegaly for the presence of polyps, those with polyps were older, had higher levels of insulin-like growth factor (IGF-1), were of male sex, and skin tags were more common (p = 0.016, p = 0.034, p = 0.006 and p = 0.001, respectively). There were no colorectal malignancies in the patients with active acromegaly. The frequency of hyperplastic polyps was increased, whereas colonic malignancy was not observed in Turkish patients with active acromegaly.


Scaling of individual phosphorus flux by caterpillars of the whitemarked tussock moth, Orygia leucostigma.
We conducted a laboratory study to evaluate the effects of body mass, environmental temperature, and food quality on phosphorus (P) efflux by caterpillars of the whitemarked tussock moth, Orygia leucostigma, J. E. Smith (Lepidoptera: Lymantriidae). We found that individual phosphorus efflux rate (Q the rate at which excreted and unassimilated P was egested in frass, mgP/day) was related to larval mass (M, mg dry) and environmental temperature (T,K) as Q = e(14.69) M(1.00)e(-0.54/kT), where K is Boltzmann's constant (8.62 x 10(-5) eV/K, 1 eV = 1.60 x 10-19J). We also found that P efflux was not related to food phosphorous concentration, and suggest that this result was due to compensatory feeding by larvae eating low quality leaves. The P efflux model resulting from this analysis was simple and powerful. Thus, it appears that this type of model can be used to scale P flux from individual larvae to the population level and link species of insect herbivores to ecosystem processes.


Filtered beauty in Oslo and Tokyo: A spatial frequency analysis of facial attractiveness.
Images of European female and male faces were digitally processed to generate spatial frequency (SF) filtered images containing only a narrow band of visual information within the Fourier spectrum. The original unfiltered images and four SF filtered images (low, medium-low, medium-high and high) were then paired in trials that kept constant SF band and face gender and participants made a forced-choice decision about the more attractive among the two faces. In this way, we aimed at identifying those specific SF bands where forced-choice preferences corresponded best to forced-choice judgements made when viewing the natural, broadband, facial images. We found that aesthetic preferences dissociated across SFs and face gender, but similarly for participants from Asia (Japan) and Europe (Norway). Specifically, preferences when viewing SF filtered images were best related to the preference with the broadband face images when viewing the highest filtering band for the female faces (about 48-77 cycles per face). In contrast, for the male faces, the medium-low SF band (about 11-19 cpf) related best to choices made with the natural facial images. Eye tracking provided converging evidence for the above, gender-related, SF dissociations. We suggest greater aesthetic relevance of the mobile and communicative parts for the female face and, conversely, of the rigid, structural, parts for the male face for facial aesthetics.


The devil is in the details: genetic variation in introduced populations and its contributions to invasion.
The influence of genetic variation on invasion success has captivated researchers since the start of the field of invasion genetics 50 years ago. We review the history of work on this question and conclude that genetic variation-as surveyed with molecular markers-appears to shape invasion rarely. Instead, there is a significant disconnect between marker assays and ecologically relevant genetic variation in introductions. We argue that the potential for adaptation to facilitate invasion will be shaped by the details of genotypes affecting phenotypes, and we highlight three areas in which we see opportunities to make powerful new insights. (i) The genetic architecture of adaptive variation. Traits shaped by large-effect alleles may be strongly impacted by founder events yet more likely to respond to selection when genetic drift is strong. Large-effect loci may be especially relevant for traits involved in biotic interactions. (ii) Cryptic genetic variation exposed during invasion. Introductions have strong potential to uncover masked variation due to alterations in genetic and ecological environments. (iii) Genetic interactions during admixture of multiple source populations. As divergence among sources increases, positive followed by increasingly negative effects of admixture should be expected. Although generally hypothesized to be beneficial during invasion, admixture is most often reported among sources of intermediate divergence, supporting the possibility that incompatibilities among divergent source populations might be limiting their introgression. Finally, we note that these details of invasion genetics can be coupled with comparative demographic analyses to link genetic changes to the evolution of invasiveness itself.


Meningococcal X polysaccharide quantification by high-performance anion-exchange chromatography using synthetic N-acetylglucosamine-4-phosphate as standard.
A method for meningococcal X (MenX) polysaccharide quantification by high-performance anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) is described. The polysaccharide is hydrolyzed by strong acidic treatment, and the peak of glucosamine-4-phosphate (4P-GlcN) is detected and measured after chromatography. In the selected conditions of hydrolysis, 4P-GlcN is the prevalent species formed, with GlcN detected for less than 5% in moles. As standard for the analysis, the monomeric unit of MenX polysaccharide, N-acetylglucosamine-4-phosphate (4P-GlcNAc), was used. This method for MenX quantification is highly selective and sensitive, and it constitutes an important analytical tool for the development of a conjugate vaccine against MenX.


Dietary greenhouse gas emissions of meat-eaters, fish-eaters, vegetarians and vegans in the UK.
The production of animal-based foods is associated with higher greenhouse gas (GHG) emissions than plant-based foods. The objective of this study was to estimate the difference in dietary GHG emissions between self-selected meat-eaters, fish-eaters, vegetarians and vegans in the UK. Subjects were participants in the EPIC-Oxford cohort study. The diets of 2,041 vegans, 15,751 vegetarians, 8,123 fish-eaters and 29,589 meat-eaters aged 20-79 were assessed using a validated food frequency questionnaire. Comparable GHG emissions parameters were developed for the underlying food codes using a dataset of GHG emissions for 94 food commodities in the UK, with a weighting for the global warming potential of each component gas. The average GHG emissions associated with a standard 2,000 kcal diet were estimated for all subjects. ANOVA was used to estimate average dietary GHG emissions by diet group adjusted for sex and age. The age-and-sex-adjusted mean (95 % confidence interval) GHG emissions in kilograms of carbon dioxide equivalents per day (kgCO2e/day) were 7.19 (7.16, 7.22) for high meat-eaters ( > = 100 g/d), 5.63 (5.61, 5.65) for medium meat-eaters (50-99 g/d), 4.67 (4.65, 4.70) for low meat-eaters ( < 50 g/d), 3.91 (3.88, 3.94) for fish-eaters, 3.81 (3.79, 3.83) for vegetarians and 2.89 (2.83, 2.94) for vegans. In conclusion, dietary GHG emissions in self-selected meat-eaters are approximately twice as high as those in vegans. It is likely that reductions in meat consumption would lead to reductions in dietary GHG emissions.


Readiness to be physically active and self-reported physical activity in low-income Latinas, California WISEWOMAN, 2006-2007.
Latinas are more likely to be inactive than non-Hispanic white women. Although 74% of Latinas report no leisure-time activity, few interventions have been designed to promote physical activity among these women. The objective of this study was to assess the effect of the California WISEWOMAN program on low-income Latinas's readiness to change physical activity and on self-reported physical activity behaviors. We screened 1,332 women for cardiovascular disease risk factors and randomly assigned 1,093 women to 2 groups: an enhanced intervention (n = 552) or usual care (n = 541). The enhanced intervention was delivered by community health workers in one-on-one counseling sessions. We examined self-reported readiness to change and physical activity at baseline and 12-month follow-up among participants who completed both assessments (n = 868). Mean age of participants was 52 years (standard deviation, 6 y); most (65%) were Mexican or Mexican American, and most (81%) were not high school graduates. A higher percentage (67%) of the enhanced intervention group was in the action/maintenance stage for vigorous physical activity at follow-up compared with baseline (47%). We found no such change among women in usual care (52%, baseline; 58%, follow-up). A higher percentage of the enhanced intervention group also reported significant increases in moderate (71%, baseline; 84%, follow-up) and vigorous (13% to 33%) physical activity at follow-up than at baseline. Women in usual care reported no changes. A culturally tailored adaptation of the WISEWOMAN program that used community health workers significantly improved both self-reported readiness to engage in physical activity and vigorous physical activity among low-income Latinas.


Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.
This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.


SU-E-T-641: Flattening Filter Free Dynamic Conformal Arcs for Lung Radiotherapy.
To investigate the use of dynamic conformal arcs (DCA) with the flattening filter free (FFF) beams for lung stereotactic body radiotherapy (SBRT) on the TrueBeam STx (Varian, Inc., Palo Alto, CA). Eight SBRT patients receiving 10-18 Gy per fraction were planned in Eclipse 10 (Varian Medical Systems, Palo Alto, CA) for the TrueBeam STx using DCA's with 6 MV FFF beams. The isocenter was placed such that the point fell near midline on each patient allowing full arc rotation without patient collision.Several planning methods were employed depending on the location of the tumor. For peripheral tumors a single arc was used. For peripheral tumors with chestwall interference, additional oblique fields were used to help pull dose off of the chestwall. For tumors located in the central region or close to the spine, multiple DCA's were used. One standard open DCA was used to deliver the majority of the dose, then one or two additional DCA's with organs blocked automatically using the'Fit and Shield' feature of Eclipse were used to help shape the dose. The arcs were then weighted to create the desired dose distribution. Beam on times for the 8 patients averaged 2.00 minutes with a minimum time of 1.22 minutes and a maximum time of 3.3 minutes total. With multiple arcs or additional static fields, treatment time is lengthened by the time it takes to mode up between arcs (∼1 minute) and/or move between fields. The PTV coverage of the 100% isodose line was >= 95% in all cases. The conformality index ranged 1.12 - 4.5, with an average of 2.5. FFF DCA is a fast, efficient way to plan and delivery SBRT treatments. The short treatment times directly lead to reduced patient motion and discomfort, which may yield improved targeting and outcomes.


Ubiquitination, protein turnover, and long-term synaptic plasticity.
For at least half a century, alteration of synaptic strength through growth at specific nerve terminals has been favored as the mechanism underlying long-term changes in behavior and synaptic plasticity. Although new proteins for synapses can either be synthesized locally or transported from the cell body, recent work on the postsynaptic element (dendritic spines) of cortical excitatory synapses indicates that transmission can also be modified by controlling the density of alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid receptors (AMPARs) in the postsynaptic density (PSD). This regulation is mediated by mono-ubiquitination, which governs turnover of AMPAR subunits by determining whether the endocytosed subunits are sent to lysosomes to be degraded or recycled back to the membrane by exocytosis. Also important is activity-dependent multi-ubiquitination and degradation of proteins that make up the scaffolding complexes that confine receptors to the PSD.


Multiple growth hormone-binding proteins are expressed on insulin-producing cells.
The insulin-producing rat islet tumor cell line, RIN-5AH, expresses somatogen binding sites and responds to GH by increased proliferation and insulin production. Affinity cross-linking shows that RIN-5AH cells contain two major GH-binding subunits of Mr 100-130K (110K), which appear to exist as disulfide-linked multimers of Mr 270-350K (300K). In addition, a minor Mr 180K GH-binding protein is identified which does not appear to be associated with other proteins by disulfide bridges. A plasma membrane-enriched fraction accounts for 86% of the RIN-cell GH-binding activity while cytosol and intracellular organelles are low in GH-binding activity. The plasma membrane-bound activity is soluble in Triton X-100 with intact hormone binding characteristics. The apparent KD in detergent solution is estimated to 18 ng/ml (8 x 10(-10) M). 125I-hGH-affinity cross-linking to intact and detergent-solubilized membranes as well as hGH-affinity purified protein reveals labeled proteins of Mr 180K and Mr 285-350K. In contrast to the cross-linked Mr 300K complexes of intact cells those of disintegrated cellular material are resistant to reduction with dithiothreitol, and it is speculated that this is due to intersubunit cross-linking of the disulfide-linked Mr 110K GH-binding subunits. The GH-binding proteins are purified approximately 100-fold by one cycle of hGH-affinity chromatography and five major proteins of Mr 180K, 94K, 86K, 64K, and 54K are identified by silver staining in the purified fraction. It is concluded that the RIN-5AH cells have multiple GH-binding proteins which may mediate signals for either proliferation and/or insulin production.