Site-directed mutagenesis of Moloney murine leukemia virus reverse transcriptase. Demonstration of lysine 103 in the nucleotide binding site.
Lys103 and Lys421 of Moloney murine leukemia virus reverse transcriptase have been implicated in the dNTP binding function as judged by their reactivity to a substrate binding site-directed reagent, pyridoxal 5'-phosphate (Basu, A., Nanduri, V. B., Gerard, G. F., and Modak, M. J. (1988) J. Biol. Chem. 263, 1648-1653). To assess the true catalytic importance of the individual lysine residues in Moloney murine leukemia virus reverse transcriptase, we mutated Lys103 and Lys421 to leucine and alanine, respectively. Analysis of the mutant enzymes revealed that mutation at the 103 position had a drastic effect on the DNA polymerase activity whereas the 421 mutation had no effect. Both mutants exhibited normal RNase H activity as well as the ability to bind to RNA or DNA templates as judged by UV-mediated cross-linking of the enzyme to the template primers. The enzyme with mutation at codon 421 (Lys----Ala) exhibited properties that were indistinguishable from the wild type with respect to its mode of catalysis, i.e. preference of template primer and divalent metal ion, RNA- or DNA-dependent DNA polymerase activity, RNase H activity, and the processive mode of DNA synthesis. These observations suggest that only Lys103 and not Lys421 is the catalytically important residue that is involved in the binding of substrate dNTP in Moloney murine leukemia virus reverse transcriptase.


Reliability and Validity of a Novel Approach to Measure Hip Rotation.
Currently, hip-rotation range of motion (ROM) is clinically measured in an open kinetic chain in either seated or prone position using passive or active ROM. However, during activities of daily living and during sports participation the hip must be able to rotate in a loaded position, and there is no standard measurement for this. To determine if a novel method for measuring hip rotation in weight bearing will result in good to very good reliability as demonstrated by an intraclass correlation coefficient (ICC) of >.80 and to investigate if weight-bearing hip measurements will result in significantly reduced hip ROM compared with non-weight-bearing methods. Repeated measures. Outpatient sports physical therapy clinic. 20 healthy participants (10 men, 10 women) recruited for hip-rotation measurements. Three trials of both internal and external rotation were measured in sitting, prone, and weight bearing. Two therapists independently measured each participant on the same day. The participants returned the following day to repeat the same measurements with the same 2 therapists. Degrees of hip internal and external rotation measured in prone, sitting, and loaded positions. In general, the measurement of hip ROM across the different conditions was reliable. The intrarater reliability was .67-.95, while interrater reliability was .59-.96. Interrater reliability was improved when values were averaged across the measures (.75-.97). ICCs for active loaded ROM were .67-.81, while interrater ICCs were .53-.87. In general, prone hip ROM was greater than supine and supine was greater than loaded. Loaded hip rotation can be measured in a clinical setting with moderate to good reliability. The rotation ROM of a loaded hip can be significantly decreased compared with unloaded motion.


Chromatin remodelling during development.
New methods for the genome-wide analysis of chromatin are providing insight into its roles in development and their underlying mechanisms. Current studies indicate that chromatin is dynamic, with its structure and its histone modifications undergoing global changes during transitions in development and in response to extracellular cues. In addition to DNA methylation and histone modification, ATP-dependent enzymes that remodel chromatin are important controllers of chromatin structure and assembly, and are major contributors to the dynamic nature of chromatin. Evidence is emerging that these chromatin-remodelling enzymes have instructive and programmatic roles during development. Particularly intriguing are the findings that specialized assemblies of ATP-dependent remodellers are essential for establishing and maintaining pluripotent and multipotent states in cells.


Expression of the oncogenes mil and ras abolishes the in vivo differentiation of mammary epithelial cells.
Three carcinoma-associated oncogenes, two of which have been strongly implicated in human mammary tumorigenesis, have been introduced into a novel mouse mammary epithelial cell line, EF43, that retains many differentiated functions. The effect of oncogene expression upon classical transformation parameters as well as parameters specific for mammary epithelial cells such as growth in three-dimensional collagen matrices and the ability to repopulate the cleared mammary fat pad and to form alveolar structures in vivo has been investigated. Expression of v-myc in EF43 cells results in no obvious phenotypic changes, and does not confer tumorigenic potential upon the cells. Expression of v-Ha-ras confers upon EF43 cells the ability to grow rapidly, grow in an anchorage-independent manner, results in tumor formation in nude and syngeneic animals, abolishes their ability to repopulate the mammary gland and, instead, results in rapid induction of anaplastic tumors. The v-mil oncogene, an avian homolog of the mouse v-mht and human c-raf oncogenes, previously thought to be non-transforming in the absence of a co-operating oncogene, transforms EF43 cells, allowing them to grow in an anchorage-independent manner, form tumors in nude mice and abolishes their ability to repopulate the cleared mammary fat pad. In contrast to v-ras, however, the tumors arising from v-mil expression have a differentiated morphology, typical of adenocarcinomas. Thus, different oncogenes show varying degrees of inhibition of the differentiation of mammary epithelial cells in vivo.


Results after lumbar decompression with and without discectomy: comparison of the transspinous and conventional approaches.
To evaluate the efficacy of the transspinous approach compared with the conventional approach in single-level lumbar laminotomies with and without discectomies. Forty consecutive patients underwent single-level lumbar decompression with or without a discectomy. The first 20 patients underwent surgery by the conventional approach (11 with discectomy and 9 without), and the transspinous approach was used in the remaining 20 patients (11 with discectomy and 9 without). Results between the groups were assessed by comparing the following measures: length of inpatient hospital stay, postoperative pain and analgesia use, estimated blood loss, rate of postoperative disability and complications, and incision length. The groups did not differ significantly with respect to age, level of pathology, insurance status, or type of analgesia used. The primary outcome was physical disability, measured using the Roland-Morris Disability Questionnaire. The secondary outcome was pain intensity, measured using the Brief Pain Inventory. Patients who underwent the transspinous approach had better outcomes across all measures with significance appreciated in those who underwent transspinous decompression with discectomies. Other statistically significant differences were identified in incision length and postoperative analgesia use at the end of 1 week. No statistically significant differences were identified in the rates of complications, estimated blood loss, inpatient narcotic analgesia use, or length of inpatient hospital stay. Patients who underwent single-level lumbar decompression with or without discectomy had similar outcomes as those who underwent the conventional approach. Although of modest clinical significance, the transspinous approach may afford early mobilization and reduced postoperative pain while providing a satisfactory neurological and functional outcome.


An Evaluation of Retentive Ability and Deformation of Acetal Resin and Cobalt-Chromium Clasps.
To compare the retentive ability and deformation of Acetal resin with Cobalt-Chromium clasps via Insertion Removal apparatus after subjecting them to stimulate clinical use. Materials used for this study are commercially available Cobalt-Chromium alloy namely Wironit, Bego, Germany and Acetal resin namely Biodentaplast, Bredent, Germany. The test samples were divided into two major groups based on the type of materials used in the study. Each major group is further subdivided into two sub groups based on the retentive undercut depths used to engage the clasps. So a total of 20 specimens were prepared, comprising of 5 specimens in each sub group. Then the specimens were tested for retention force and deformation. The results of this study indicate that acetal resin clasps are resistant to deformation and may offer a clinical advantage over the conventional metal clasps. The retentive force of acetal resin clasps did not decrease over the cycling periods. This would be attributed to the resilient nature of acetal resin. Under the conditions of the present study cobalt chromium clasps lost retentive force within 730 cycles of placement and removal and continued to lose retentive force during the remaining test period. This invitro study demonstrated that retentive force of cobalt chromium clasp is superior to that of Acetal resin for removable partial dentures. As acetal resin clasps exhibits greater flexibility and long term retentive resiliency, it can be used for removable partial dentures where aesthetics or periodontal health is a primary concern.


The State of the Science of Health Literacy Measurement.
Advancing health literacy (HL) research requires high-quality HL measures. This chapter provides an overview of the state of the science of HL measurement: where the field started, currently is, and should be going. It is divided into eight key sections looking at (1) the history of HL measurement, (2) the relationship between HL definitions and measurement, (3) the HL conceptual domains most and least frequently measured, (4) the methods used to validate HL measures, (5) the characteristics of the participants in the measurement validation studies, (6) the practical considerations related to administering HL measures, (7) the advantages and disadvantages of using objective versus subjective HL measures, and (8) future directions for HL measurement. Based on the material presented in this chapter, the following conclusions can be drawn. First, there is an enormous proliferation of HL measures and this growth presents both opportunities and challenges for the field. Second, to move the field forward, there is an urgent need to better align HL measurement with definitions of HL. Third, some HL domains, such as numeracy, are measured more often than others, such as speaking and listening. Consequently, it is important to think about novel mechanisms to measure HL domains that are rarely measured. Fourth, HL measures are most often developed, validated, and refined using classical measurement approaches. However, strong empirical and practical rationales suggest making an assertive shift toward using modern measurement approaches. Fifth, most HL measures are not well validated for use in minority populations; consequently, future validation studies should be mindful of validation samples. Sixth, HL measures can be administered using multiple modes, most frequently via paper-and-pencil surveys. Identifying which mode of administration is most suitable requires reflecting on the underlying measurement purpose and the characteristics of the participants being measured. These considerations should also be made when deciding between a subjective versus objective HL measure. Cumulatively, this chapter provides tools to help readers select and use the most appropriate measures of HL for their needs. It also provides rationale and strategies for moving the science of HL measurement forward.


A right antenna for social behaviour in honeybees.
Sophisticated cognitive abilities have been documented in honeybees, possibly an aspect of their complex sociality. In vertebrates brain asymmetry enhances cognition and directional biases of brain function are a putative adaptation to social behaviour. Here we show that honeybees display a strong lateral preference to use their right antenna in social interactions. Dyads of bees tested using only their right antennae (RA) contacted after shorter latency and were significantly more likely to interact positively (proboscis extension) than were dyads of bees using only their left antennae (LA). The latter were more likely to interact negatively (C-responses) even though they were from the same hive. In dyads from different hives C-responses were higher in RA than LA dyads. Hence, RA controls social behaviour appropriate to context. Therefore, in invertebrates, as well as vertebrates, lateral biases in behaviour appear to be associated with requirements of social life.


Nrf2 establishes a glutathione-mediated gradient of UVB cytoprotection in the epidermis.
Ultraviolet (UV) B irradiation can severely damage the skin and even induce tumorigenesis. It exerts its effects by direct DNA modification and by formation of reactive oxygen species (ROS). We developed a strategy to genetically activate target gene expression of the transcription factor NF-E2-related factor 2 (Nrf2) in keratinocytes in vivo based on expression of a constitutively active Nrf2 mutant. Activation of Nrf2 target genes strongly reduced UVB cytotoxicity through enhancement of ROS detoxification. Remarkably, the protective effect was extended to neighboring cells. Using different combinations of genetically modified mice, we demonstrate that Nrf2 activates the production, recycling, and release of glutathione and cysteine by suprabasal keratinocytes, resulting in protection of basal cells in a paracrine, glutathione/cysteine-dependent manner. Most importantly, we found that endogenous Nrf2 controls selective protection of suprabasal keratinocytes from UVB-induced apoptosis through activation of cytoprotective genes. This finding explains the preferential UVB-induced apoptosis of basal cells, which is important for elimination of mutated stem cells as well as for preservation of skin integrity. Taken together, our results identify Nrf2 as a key regulator in the UV response of the skin.


[Strategies by Mexican migrants in the USA to seek health care].
To identify the strategies used by Mexican migrants to access health services in the U.S. and Mexico. Ethnographic study in five Mexican states, selected by their migration dynamics. A series of focus groups and in-depth interviews were conducted with health services users and providers. Six strategies were identified and are used according to the severity of the disease: a) self-medication, b) telephone consultation with relatives, c) utilization of private services, d) travel to border towns, e) return to place of birth, f) getting medical care during their visits to places of origin. The health care options used by Mexican migrants and their families are defined according to events related to the migration process. The implementation of public policies to protect the health of migrants on both sides of the border is critical.


Summary statistic analyses can mistake confounding bias for heritability.
Linkage disequilibrium SCore regression (LDSC) has become a popular approach to estimate confounding bias, heritability, and genetic correlation using only genome-wide association study (GWAS) test statistics. SumHer is a newly introduced alternative with similar aims. We show using theory and simulations that both approaches fail to adequately account for confounding bias, even when the assumed heritability model is correct. Consequently, these methods may estimate heritability poorly if there was an inadequate adjustment for confounding in the original GWAS analysis. We also show that the choice of a summary statistic for use in LDSC or SumHer can have a large impact on resulting inferences. Further, covariate adjustments in the original GWAS can alter the target of heritability estimation, which can be problematic for test statistics from a meta-analysis of GWAS with different covariate adjustments.


Parent Perceptions of Trainees in Pediatric Care: Cross-Sectional Study.
Clinical experience and progressive autonomy are essential components of medical education and must be balanced with patient comfort. While previous studies have suggested that most patients accept trainee involvement in their care, few studies have focused specifically on the views of parents of pediatric patients or examined groups who may not report acceptance. This study aims to understand parental profiles of resident and medical student involvement in pediatric care and to use latent class analysis (LCA) methodology to identify classes of responses associated with parent demographic characteristics. We used data from a national cross-sectional web-based survey of 3000 parents. The survey used a 5-point Likert scale to assess 8 measures of parent perceptions of residents and medical students. We included participants who indicated prior experience with residents or medical students. We compared responses about resident involvement in pediatric care with responses about student involvement, used LCA to identify latent classes of parent responses, and compared demographic features between the latent classes. Of the 3000 parents who completed the survey, 1543 met the inclusion criteria for our study. Participants reported higher mean scores for residents than for medical students for perceived quality of care, comfort with autonomously performing an examination, and comfort with autonomously giving medical advice. LCA identified 3 latent classes of parent responses: Trainee-Hesitant, Trainee-Neutral, and Trainee-Supportive. Compared with the Trainee-Supportive and Trainee-Neutral classes, the Trainee-Hesitant class had significantly more members reporting age <30 years, household income < US $50,000, no college degree, and lesser desire to receive future care at a teaching hospital (all P<.05). Parents may prefer greater clinical autonomy for residents than medical students. Importantly, views associated with the Trainee-Hesitant class may be held disproportionately by members of historically and currently socially marginalized demographic groups. Future studies should investigate underlying reasons for trainee hesitancy in these groups, including the possibility of mistrust in medicine.


Dimeric beta-turn peptidomimetics as ligands for the neurotrophin receptor TrkC.
Twelve dimeric peptidomimetics 1 were prepared via a divergent-convergent strategy. These peptidomimetics incorporated the same amino acids as i +1 and i + 2 residues in key beta-turns of the neurotrophin NT-3. Cytosensor microphysiometry was used to gauge the effects of the dimers 1 on cells that overexpress the NT-3 receptor, TrkC. Increases in extracellular acidification rates were observed for some monomers 3, but the active dimers gave greater effects.


Modafinil : a review of its use in excessive sleepiness associated with obstructive sleep apnoea/hypopnoea syndrome and shift work sleep disorder.
Modafinil (Provigil is a wake-promoting agent that is pharmacologically distinct from CNS stimulants, such as amfetamine, dexamfetamine and methylphenidate. Modafinil is approved for use in the US and certain European countries for use in patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea/hypopnoea syndrome (OSA/HS) or shift work sleep disorder (SWSD). Oral modafinil promotes wakefulness in patients with OSA/HS and SWSD. It is an effective adjunctive therapy in patients with residual excessive sleepiness associated with OSA/HS who are receiving nasal continuous positive airway pressure (nCPAP) therapy. In SWSD, the drug improves night-time wakefulness without disrupting daytime sleep. Modafinil is generally well tolerated in patients with OSA/HS or SWSD and has a low abuse potential. Thus, modafinil is a valuable new treatment option for use in patients with excessive sleepiness associated with OSA/HS (as an adjunct to nCPAP) or SWSD.


Non-malignant respiratory diseases and occupational exposure to wood dust. Part II. Dry wood industry.
This paper reviews the literature on associations between dry wood dust exposure and non-malignant respiratory diseases. Criteria for inclusion are epidemiological studies in English language journals with an internal or external control group describing relationships between dry wood dust exposure and respiratory diseases or symptoms. Papers took into consideration smoking and when dealing with lung function age. A total of 37 papers forms the basis of this review. The results support an association between dry wood dust exposure and asthma, asthma symptoms, coughing, bronchitis, and acute and chronic impairment of lung function. In addition, an association between wood dust exposure and rhino-conjunctivitis is seen across the studies. Apart from plicatic acid in western red cedar wood, no causal agent has consistently been disclosed. Type 1 allergy is not suspected to be a major cause of wood dust induced asthma.


Loss of air sacs improved hominin speech abilities.
In this paper, the acoustic-perceptual effects of air sacs are investigated. Using an adaptive hearing experiment, it is shown that air sacs reduce the perceptual effect of vowel-like articulations. Air sacs are a feature of the vocal tract of all great apes, except humans. Because the presence or absence of air sacs is correlated with the anatomy of the hyoid bone, a probable minimum and maximum date of the loss of air sacs can be estimated from fossil hyoid bones. Australopithecus afarensis still had air sacs about 3.3 Ma, while Homo heidelbergensis, some 600 000 years ago and Homo neandethalensis some 60 000 years ago, did no longer. The reduced distinctiveness of articulations produced with an air sac is in line with the hypothesis that air sacs were selected against because of the evolution of complex vocal communication. This relation between complex vocal communication and fossil evidence may help to get a firmer estimate of when speech first evolved.


Evaluating Initial Integration of Cell-Based Chondrogenic Constructs in Human Osteochondral Explants.
Integration of an implant with the surrounding tissue is a major challenge in cartilage regeneration. It is usually assessed with in vivo animal studies at the end-stage of implant development. To reduce animal experimentation and at the same time increase screening throughput and speed up implant development, this study examined whether integration of allogeneic cell-based implants with the surrounding native cartilage could be demonstrated in an ex vivo human osteochondral culture model. Chondrocytes were isolated from smooth cartilage tissue of fresh human tibial plateaus and condyles. They were expanded for 12 days either in three-dimensional spinner flask cultures to generate organoids, or in two-dimensional culture flasks for standard cell expansion. Three implant groups were created (fibrin+organoids, fibrin+cells, and fibrin only) and used to fill a Ø 6 mm full-depth chondral defect created in human osteochondral explants (Ø 10 mm, bone length cut to 4 mm) harvested from a second set of fresh human tibial plateaus. Explants were cultured for 1 or 28 days in a double-chamber culture platform. Histology showed that after 28 days the organoids on the interface of the defect remodeled and merged, and cells migrated through the fibrin glue bridging the space between the organoids and between the organoids and the native cartilage. For both conditions, newly formed tissue rich in proteoglycans and collagen type II was present mainly on the edges and in the corners of the defect. In these matrix-rich areas, cells resided in lacunae and the newly formed tissue integrated with the surrounding native cartilage. Biochemical analysis revealed a statistically significant effect of culture time on glycosaminoglycan (GAG) content, and showed a higher hydroxyproline (HYP) content for organoid-filled implants compared with cell-filled implants at both timepoints. This ex vivo human osteochondral culture system provides possibilities for exploration and identification of promising implant strategies based on evaluation of integration and matrix production under more controlled experimental conditions than possible in vivo.


Time encoding and reconstruction of multichannel data by brain implants using asynchronous sigma delta modulators.
Recently, information technology and microelectronics have enabled implanting miniature and highly intelligent devices within the brain for in-vitro diagnostic and therapeutic functions. Power and physical size constraints of these devices necessitate novel signal processing methods. In this paper we investigate an effective data acquisition and reconstruction method for brain implants based on Asynchronous Sigma Delta Modulators (ASDMs). The ASDMs are analog non-linear feedback systems capable of time coding signals. The proposed reconstruction algorithm is based on the Prolate Spheroidal Wave Function (PSWF) expansion of the sinc functions and the order of expansion is given by the input signal being coded. Multiplexing and transmission of the different channels of data are accomplished by chirp orthogonal frequency division multiplexing. Computer simulations using multi channel electroencephalographic data are performed for wireless transmission by brain implants for monitoring abnormal brain activities of epilepsy patients.


COVID-19 Coinfection with Mycobacterium abscessus in a Patient with Multiple Myeloma.
Coronavirus disease (COVID-19) is a worldwide pandemic causing multiple fatalities and morbidities worldwide. We report a case of severe pneumonia causing acute respiratory distress syndrome due to a coinfection with SARS-CoV-2 and Mycobacterium abscessus in an elderly patient with multiple myeloma in Florida, USA. Case Presentation. An 84-year-old male with a medical history significant for multiple myeloma not in remission was sent to the emergency department to rule out COVID-19 infection prior to continuing his chemotherapy sessions. At presentation, he had nonspecific mild symptoms and an unremarkable physical examination. He had significant blood test findings including serum lactate dehydrogenase 373 U/L, high sensitive C-reactive protein 17.40 mg/l, and ferritin 415 ng/ml. Xpert-SARS-CoV-2 was positive. Chest radiograph revealed patchy areas of interstitial infiltrates in mid to lower lung zones. During his hospitalization course, his oxygenation deteriorated, requiring mechanical intubation. Repeat chest radiograph showed worsening bilateral infiltrates. He was started on broad-spectrum antibiotics and eventually weaned off mechanical intubation and extubated. On the 11th day of admission, he was found to be bradycardic and in shock, and he was reintubated. His labs showed worsening inflammatory markers along with kidney dysfunction to the point of requiring renal replacement therapy. He received both convalescent plasma and remdesivir for treatment of COVID-19 pneumonia. Eventually, repeat blood cultures came back positive for the growth of acid-fast beaded bacilli. While awaiting final culture and sensitivity reports, his antibiotics were upgraded to cover possible nocardia infection. Repeat blood and sputum cultures resulted in growth of AFB bacilli Mycobacterium abscessus 1 week after. This case report highlights the importance of keeping a broad differential and considering multiple coinfections, including atypical ones during this COVID-19 pandemic, such as the one that was discussed above, Mycobacterium abscessus, in order to provide goal-directed therapy.


Respiratory syncytial virus: a systematic scientometric analysis of the global publication output and the gender distribution of publishing authors.
Worldwide, the respiratory syncytial virus (RSV) represents the predominant viral agent causing bronchiolitis and pneumonia in children. To conduct research and tackle existing healthcare disparities, RSV-related research activities around the globe need to be described. Hence, we assessed the associated scientific output (represented by research articles) by geographical, chronological and socioeconomic criteria and analysed the authors publishing in the field by gender. Also, the 15 most cited articles and the most prolific journals were identified for RSV research. Retrospective, descriptive study. The NewQIS (New Quality and Quantity Indices in Science) platform was employed to identify RSV-related articles published in the Web of Science until 2013. We performed a numerical analysis of all articles, and examined citation-based aspects (eg, citation rates); results were visualised by density equalising mapping tools. We identified 4600 RSV-related articles. The USA led the field; US-American authors published 2139 articles (46.5%% of all identified articles), which have been cited 83 000 times. When output was related to socioeconomic benchmarks such as gross domestic product or Research and Development expenditures, Guinea-Bissau, The Gambia and Chile were ranked in leading positions. A total of 614 articles on RSV (13.34% of all articles) were attributed to scientific collaborations. These were primarily established between high-income countries. The gender analysis indicated that male scientists dominated in all countries except Brazil. The majority of RSV-related research articles originated from high-income countries whereas developing nations showed only minimal publication productivity and were barely part of any collaborative networks. Hence, research capacity in these nations should be increased in order to assist in addressing inequities in resource allocation and the clinical burden of RSV in these countries.


Recalcitrant rhinosinusitis, innate immunity, and mannose-binding lectin.
Mannose-binding lectin (MBL) is a protein produced by the liver that participates in innate immunity by tagging the surface of microbes for opsonization. Mannose-binding lectin deficiency is present in 7% of the population and has been implicated in recurrent respiratory tract infections in children. Mannose-binding lectin deficiency has not been explored in rhinosinusitis but is associated with increased mortality in adult pneumococcal infection. The purpose of this report is to describe a tertiary rhinology patient experience with MBL deficiency and recalcitrant rhinosinusitis. This retrospective case series report characterizes predominantly adult patients with low MBL levels from January 2010 to June 2012. Indications for MBL testing, sinus culture data, immunological testing results, and treatments used to control rhinosinusitis are described. Mannose-binding lectin levels were deficient in 12 of 36 patients (33.3%) tested. IgG subclasses were abnormally low in 5 of 12 patients; IgA was normal in 11 of 12 patients; and IgM was normal in 11 of 12 patients. Staphylococcus aureus, coagulase-negative Staphylococcus species, and Pseudomonas aeruginosa, known to be "tagged" by MBL, were the most common organisms grown on culture. Treatments included culture directed systemic antimicrobial therapy and topical steroids/antibiotics. Mannose-binding lectin, an important component of the lectin complement pathway and innate immunity, is possibly associated with recalcitrant adult rhinosinusitis. Steroid/antibiotic irrigations appear to benefit patients with recalcitrant rhinosinusitis and possibly those with MBL deficiency. Given that the prevalence of MBL deficiency in this case series is 4 times that seen in the normal population, additional investigations are warranted to further elucidate the role of MBL deficiency in rhinosinusitis.


Are aggressive people aggressive drivers? A study of the relationship between self-reported general aggressiveness, driver anger and aggressive driving.
In this study the relationships among self-reported general aggressiveness, impulsiveness, driver anger, and aggressive responses to anger-provoking situations on the road were studied. The British version of a driver anger scale (UK DAS), aggression questionnaire (AQ), and an impulsiveness questionnaire (I7) together with background questions (gender, age, annual mileage) were administered to a sample of 270 British drivers. Variation in strength of correlations between anger and aggressive reactions in the 21 UK DAS items showed that the relationship between driver anger and aggression depends in part on the characteristics of the situation. In addition, three path models for describing the relationships among the measures were constructed separately for women and men. The models suggested that the effects of verbal aggressiveness on self-reported driver aggression were mediated by driver anger whereas physical aggressiveness was directly related to aggressive behaviour. Age was negatively related to both driver anger and aggression among men whereas annual mileage was negatively related to aggression among women. The models constructed indicate that aggressive driver behaviour is a complex phenomenon with a range of psychological causes.


Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody.
The hyperpermeability of tumor vessels to macromolecules, compared with normal vessels, is presumably due to vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) released by neoplastic and/or host cells. In addition, VEGF/VPF is a potent angiogenic factor. Removal of this growth factor may reduce the permeability and inhibit tumor angiogenesis. To test these hypotheses, we transplanted a human glioblastoma (U87), a human colon adenocarcinoma (LS174T), and a human melanoma (P-MEL) into two locations in immunodeficient mice: the cranial window and the dorsal skinfold chamber. The mice bearing vascularized tumors were treated with a bolus (0.2 ml) of either a neutralizing antibody (A4.6.1) (492 micrograms/ml) against VEGF/VPF or PBS (control). We found that tumor vascular permeability to albumin in antibody-treated groups was lower than in the matched controls and that the effect of the antibody was time-dependent and influenced by the mode of injection. Tumor vascular permeability did not respond to i.p. injection of the antibody until 4 days posttreatment. However, the permeability was reduced within 6 h after i.v. injection of the same amount of antibody. In addition to the reduction in vascular permeability, the tumor vessels became smaller in diameter and less tortuous after antibody injections and eventually disappeared from the surface after four consecutive treatments in U87 tumors. These results demonstrate that tumor vascular permeability can be reduced by neutralization of endogenous VEGF/ VPF and suggest that angiogenesis and the maintenance of integrity of tumor vessels require the presence of VEGF/VPF in the tissue microenvironment. The latter finding reveals a new mechanism of tumor vessel regression-i.e., blocking the interactions between VEFG/VPF and endothelial cells or inhibiting VEGF/VPF synthesis in solid tumors causes dramatic reduction in vessel diameter, which may block the passage of blood elements and thus lead to vascular regression.


Extensive Alternative Splicing of KIR Transcripts.
The killer-cell Ig-like receptors (KIR) form a multigene entity involved in modulating immune responses through interactions with MHC class I molecules. The complexity of the KIR cluster is reflected by, for instance, abundant levels of allelic polymorphism, gene copy number variation, and stochastic expression profiles. The current transcriptome study involving human and macaque families demonstrates that KIR family members are also subjected to differential levels of alternative splicing, and this seems to be gene dependent. Alternative splicing may result in the partial or complete skipping of exons, or the partial inclusion of introns, as documented at the transcription level. This post-transcriptional process can generate multiple isoforms from a single KIR gene, which diversifies the characteristics of the encoded proteins. For example, alternative splicing could modify ligand interactions, cellular localization, signaling properties, and the number of extracellular domains of the receptor. In humans, we observed abundant splicing for KIR2DL4, and to a lesser extent in the lineage III KIR genes. All experimentally documented splice events are substantiated by in silico splicing strength predictions. To a similar extent, alternative splicing is observed in rhesus macaques, a species that shares a close evolutionary relationship with humans. Splicing profiles of Mamu-KIR1D and Mamu-KIR2DL04 displayed a great diversity, whereas Mamu-KIR3DL20 (lineage V) is consistently spliced to generate a homolog of human KIR2DL5 (lineage I). The latter case represents an example of convergent evolution. Although just a single KIR splice event is shared between humans and macaques, the splicing mechanisms are similar, and the predicted consequences are comparable. In conclusion, alternative splicing adds an additional layer of complexity to the KIR gene system in primates, and results in a wide structural and functional variety of KIR receptors and its isoforms, which may play a role in health and disease.


Genome-wide association study of intracranial aneurysm identifies a new association on chromosome 7.
Common variants have been identified using genome-wide association studies which contribute to intracranial aneurysms (IA) susceptibility. However, it is clear that the variants identified to date do not account for the estimated genetic contribution to disease risk. Initial analysis was performed in a discovery sample of 2617 IA cases and 2548 controls of white ancestry. Novel chromosomal regions meeting genome-wide significance were further tested for association in 2 independent replication samples: Dutch (717 cases; 3004 controls) and Finnish (799 cases; 2317 controls). A meta-analysis was performed to combine the results from the 3 studies for key chromosomal regions of interest. Genome-wide evidence of association was detected in the discovery sample on chromosome 9 (CDKN2BAS; rs10733376: P<1.0×10(-11)), in a gene previously associated with IA. A novel region on chromosome 7, near HDAC9, was associated with IA (rs10230207; P=4.14×10(-8)). This association replicated in the Dutch sample (P=0.01) but failed to show association in the Finnish sample (P=0.25). Meta-analysis results of the 3 cohorts reached statistical significant (P=9.91×10(-10)). We detected a novel region associated with IA susceptibility that was replicated in an independent Dutch sample. This region on chromosome 7 has been previously associated with ischemic stroke and the large vessel stroke occlusive subtype (including HDAC9), suggesting a possible genetic link between this stroke subtype and IA.


Effect of provision of home-based curative health services by public sector health-care providers on neonatal survival: a community-based cluster-randomised trial in rural Pakistan.
Although the effectiveness of community mobilisation and promotive care delivered by community health workers in reducing perinatal and neonatal mortality is well established, evidence in support of home-based neonatal resuscitation and infection management is mixed. We assessed the effectiveness of adding training in neonatal bag and mask resuscitation and oral antibiotic therapy for suspected neonatal infections to a basic preventive and promotive interventions package delivered by public sector community-based lady health workers (LHWs) in rural Pakistan. We did a cluster-randomised controlled trial in two subdistricts of Naushahro Feroze in rural Sindh, Pakistan, between April 15, 2009, and Dec 10, 2012. LHWs, trained in basic newborn resuscitation and in recognition and treatment (with oral amoxicillin) of suspected neonatal respiratory infections, were linked with traditional birth attendants and encouraged to attend home births. Control clusters received routine care through the existing national programme. The primary outcome was all-cause neonatal mortality. Independent data collection teams recorded data for all pregnancies and their outcomes, morbidity, mortality, and household practices related to maternal and newborn care. Of the 27 randomised clusters with functional LHW programmes, 13 were allocated to the intervention group (n=242 749) and 14 to the control group (n=256 985). In the intervention group, LHWs did 80% of the planned community mobilisation sessions, but were able to attend only 1184 (14%) of 8425 deliveries and 4318 (25%) of 17 288 neonatal visits within 72 h of birth (p<0·0001 for both variables compared with the control group). The neonatal mortality rate was 42 deaths per 1000 livebirths in intervention clusters compared with 55 per 1000 in the control group (risk ratio 0·80, 95% CI 0·68-0·93; p=0·005). The reduction in neonatal mortality in intervention clusters occurred against a background of improvements in domiciliary practices for maternal and newborn care. However, the poor reach of LHWs in accessing newborn infants at birth and in the early postnatal period underscores the limitations of tasking community health workers in public sector programmes working in similar circumstances with such complex interventions. Such community-based interventions in health systems should be accompanied by concerted efforts to improve quality of care in facilities and referral systems. Saving Newborn Lives, Save the Children USA.


Macrophage-like Cells Are Responsive to Titania Nanotube Intertube Spacing-An In Vitro Study.
With the introduction of a new interdisciplinary field, osteoimmunology, today, it is well acknowledged that biomaterial-induced inflammation is modulated by immune cells, primarily macrophages, and can be controlled by nanotopographical cues. Recent studies have investigated the effect of surface properties in modulating the immune reaction, and literature data indicate that various surface cues can dictate both the immune response and bone tissue repair. In this context, the purpose of the present study was to investigate the effects of titanium dioxide nanotube (TNT) interspacing on the response of the macrophage-like cell line RAW 264.7. The cells were maintained in contact with the surfaces of flat titanium (Ti) and anodic TNTs with an intertube spacing of 20 nm (TNT20) and 80 nm (TNT80), under standard or pro-inflammatory conditions. The results revealed that nanotube interspacing can influence macrophage response in terms of cell survival and proliferation, cellular morphology and polarization, cytokine/chemokine expression, and foreign body reaction. While the nanostructured topography did not tune the macrophages' differentiation into osteoclasts, this behavior was significantly reduced as compared to flat Ti surface. Overall, this study provides a new insight into how nanotubes' morphological features, particularly intertube spacing, could affect macrophage behavior.


Recent advances in anxiety disorders: Focus on animal models and pathological mechanisms.
Anxiety disorders have become one of the most severe psychiatric disorders, and the incidence is increasing every year. They impose an extraordinary personal and socioeconomic burden. Anxiety disorders are influenced by multiple complex and interacting genetic, psychological, social, and environmental factors, which contribute to disruption or imbalance in homeostasis and eventually cause pathologic anxiety. The selection of a suitable animal model is important for the exploration of disease etiology and pathophysiology, and the development of new drugs. Therefore, a more comprehensive understanding of the advantages and limitations of existing animal models of anxiety disorders is helpful to further study the underlying pathological mechanisms of the disease. This review summarizes animal models and the pathogenesis of anxiety disorders, and discusses the current research status to provide insights for further study of anxiety disorders.


The Photothrombotic Model of Ischemic Stroke.
Stroke is a major cause of morbidity worldwide; yet, there is a lack of treatment options to address post-stroke cognitive and motor impairment, thus there is an urgency for developing neuroprotective and restorative therapies. Much of our fundamental understanding of stroke pathology has been derived from animal models. The photothrombotic model of ischemic stroke is commonly used to study cellular and molecular mechanisms of neurodegeneration, test functional/cognitive outcomes, identify important biomarkers, and assess the effectiveness of novel therapies. It allows for the precise targeting of an infarct to a specific region of the brain, has a low mortality rate, low seizure rate, and is relatively easy to perform. This chapter outlines materials and methods for the photothrombotic model of ischemic stroke in mice, its limitations, and some considerations needed when using this model.


A multidisciplinary team approach to improving psychosocial care in patients with cancer.
The demand for patient-centered care has reinforced the need for a systematic approach to planning appropriate psychosocial services. A proposed strategy to address this need is to use a multidisciplinary team comprised of oncology nurses, physicians, mental health professionals, social workers, ethicists, and other healthcare professionals to provide comprehensive psychosocial care to patients and their families. This article describes key aspects of a broad-based team approach used to develop evidence-based, multidisciplinary practice change that could improve psychosocial care and outcomes.


Estimating the hazards of "less hazardous" cigarettes. I. Tar, nicotine, carbon monoxide, acrolein, hydrogen cyanide, and total aldehyde deliveries of Canadian cigarettes.
The tar, nicotine, CO, HCN, total aldehyde, and acrolein deliveries of 102 brands of Canadian cigarettes have been determined. On the basis of these deliveries, 15 brands (9% of sales) were categorized as low hazard and 9 brands (10% of sales) as high hazards. All six constituents were used for the classification since for most brands tar was a poor indicator of gas-phase deliveries. As a result, smokers who indiscriminately switch to a brand with a lower tar delivery may inadvertently increase their exposure to gas-phase constituents such as CO and increase their risk of smoking-related pathology. With respect to Canadian cigarettes, the choice of a 30-mm standard butt length may result in omission of some of the available tobacco from the testing procedure, thus reducing the value of tar level as a guide to choosing a less harmful cigarette.


Promoting Oral Therapy Adherence: Consensus Statements From the Faculty of the Melanoma Nursing Initiative on Oral Melanoma Therapies .
Inhibitors of BRAF and the downstream signaling protein MEK have improved outcomes for patients with BRAF-mutant advanced malignant melanoma. Despite their ease of administration, these oral therapies pose adherence challenges. . This article aims to increase awareness of causes of nonadherence to oral targeted therapies in advanced malignant melanoma and to provide oncology nurses with strategies to address these nonadherence issues. . Members of the Melanoma Nursing Initiative explored issues related to adherence to targeted therapies in advanced malignant melanoma. The current literature and clinical experience were reviewed. . The authors present a care step pathway focused on increased patient engagement and rapid identification and optimal management of toxicities to avoid toxicity-related nonadherence. Other causes for nonadherence and employment of individualized strategies to support patient adherence are addressed.


Naturally occurring mutants of human steroid 21-hydroxylase (P450c21) pinpoint residues important for enzyme activity and stability.
Three mutants (deletion of E196, G291S, and R483P) of steroid 21-hydroxylase (P450c21) from patients with inherited congenital adrenal hyperplasia had reduced activity toward progesterone and 17-hydroxyprogesterone after transient expression in cultured mammalian cells. In addition, both the E196 deletion and the R483P mutant had shorter half-lives than the wild-type enzyme, whereas the half-life of the G291S mutant was comparable with that of the normal protein. These results directly link the clinical situation with the three mutations and suggest that G291 is important for the catalytic activity of P450c21.


Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines.
Recombinant acellular pertussis (ap) vaccines containing genetically inactivated pertussis toxin (PTgen) and filamentous hemagglutinin (FHA) with or without tetanus (TT) and diphtheria (DT) vaccines (Td) were found safe and immunogenic in non-pregnant and pregnant women. We report here maternal antibody transfer and safety data in mothers and neonates. This is the follow up of a phase 2 trial in 2019 among 400 pregnant women who randomly received one dose of recombinant pertussis-only vaccine containing 1 µg PTgen and 1 µg FHA (ap1gen), or Td combined with ap1gen (Tdap1gen), or with 2 µg PTgen and 5 µg FHA (Tdap2gen), or with 5 µg PTgen and 5 µg FHA (TdaP5gen, Boostagen®, BioNet, Thailand) or chemically-inactivated acellular pertussis comparator (Tdap8chem, Boostrix™, GSK, Belgium), either in the second or third trimester of gestation. IgG against PT, FHA, TT and DT were assessed by ELISA, PT-neutralizing antibodies (PTNA) by Chinese Hamster Ovary cell assay and safety outcomes at delivery in mothers and at birth. Anti-PT and anti-FHA geometric mean concentration (GMC) ratio between infants at birth and mothers at delivery was above 1 in all groups. PT GMC in infants at birth were ≥30 IU/mL in all groups with the highest titers in infants found in TdaP5gen group at birth (118.8 [95% CI 93.9-150.4]). At 2 months, PT GMC ratio to Tdap8chem (98.75% CI) was significantly higher for TdaP5gen (2.6 [1.7-4.0]) and comparable for other recombinant vaccines. No difference in PTNA titers at birth was observed between all groups nor between time of vaccination. Adverse events were comparable in all vaccine groups. BioNet licensed (TdaP5gen and Tdap2gen) and candidate vaccines (Tdap1gen and ap1gen) when given to pregnant women in the second or third trimester of gestation are safe and have induced passive pertussis immunity to infants.


Acupuncture for cerebral palsy: A meta-analysis of randomized controlled trials.
To evaluate the efficacy and safety of acupuncture therapy for children with cerebral palsy. We conducted electronic searches of PUBMED (1950/2017), EMBASE (1974/2017), ScienceDirect (1986/2017), Academic Source Premier (1887/2017), the Cochrane Library (Issue 4, April 2017), Science Citation Index Expanded (1900/2017), China National Knowledge Infrastructure (1915/2017), China Biological Medicine (1990/2017-04), WanFang (1980/2017), VIP (1989/2017), and Chinese Science Citation Database (1989/2017). We included randomized controlled trials that aimed to compare the effect of acupuncture plus rehabilitation training versus rehabilitation training alone. Data about functional motor abilities, daily activity/social participation, effective rate, intellectual development, and adverse effects were included. We used Revman 5.2 software for statistical analysis. The primary outcomes included functional motor abilities, daily activity, and effective rate. The secondary outcomes included intellectual development and adverse effects. Twenty-one studies with a total of 1718 participants met the inclusion criteria. The effect size of gross motor function (SMD = 0.64, 95% CI: 0.52 to 0.76, P < 0.00001; I2 = 0%, P = 0.69; in 13 studies with 1144 patients) and the total effective rate (RR = 1.28, 95% CI: 1.20 to 1.37, P < 0.00001; I2 = 18%, P = 0.27; in 12 studies with 1106 patients) suggested that acupuncture plus rehabilitation produced a significant improvement in gross motor function and a high total effective rate. The pooled fine motor function (SMD = 3.48, 95% CI: 2.62 to 4.34, P < 0.00001; I2 = 64%, P = 0.10; in 2 studies with 193 patients), modified Ashworth scale scores (SMD = -0.31, 95% CI: -0.52 to -0.11, P = 0.003; I2 = 74%, P = 0.004; in 5 studies with 363 patients) and activities of daily living (SMD = 1.45, 95% CI: 1.20 to 1.71, P < 0.00001; I2 = 78%, P = 0.004; in 4 studies with 313 patients) also indicated improvements in children with cerebral palsy. Publication bias was not observed. Only mild adverse events related to acupuncture were reported. Acupuncture plus rehabilitation training improved gross motor function, reduced muscle spasms, and enhanced daily life activities in children with cerebral palsy. However, this conclusion should be interpreted with caution due to the small number of randomized controlled trials available and the small sample sizes. More high-quality and large-scale studies are needed.


Impact of Thermal Annealing on Organic Photovoltaic Cells Using Regioisomeric Donor-Acceptor-Acceptor Molecules.
We report a promising set of donor-acceptor-acceptor (D-A-A) electron-donor materials based on coplanar thieno[3,2-b]/[2,3-b]indole, benzo[c][1,2,5]thiadiazole, and dicyanovinylene, which are found to show broadband absorption with high extinction coefficients. The role of the regioisomeric electron-donating thienoindole moiety on the physical and structural properties is examined. Bulk heterojunction (BHJ) organic photovoltaic cells (OPVs) based on the thieno[2,3-b]indole-based electron donor NTU-2, using C70 as an electron acceptor, show a champion power conversion efficiency of 5.2% under AM 1.5G solar simulated illumination. This efficiency is limited by a low fill factor (FF), as has previously been the case in D-A-A systems. In order to identify the origin of the limited FF, further insight into donor layer charge-transport behavior is realized by examining planar heterojunction OPVs, with emphasis on the evolution of film morphology with thermal annealing. Compared to as-deposited OPVs that exhibit insufficient donor crystallinity, crystalline OPVs based on annealed thin films show an increase in the short-circuit current density, FF, and power conversion efficiency. These results suggest that that the crystallization of D-A-A molecules might not be realized spontaneously at room temperature and that further processing is needed to realize efficient charge transport in these materials.


Development of a read-across-derived classification model for the predictions of mutagenicity data and its comparison with traditional QSAR models and expert systems.
Mutagenicity is considered an important endpoint from the regulatory, environmental and medical points of view. Due to the wide number of compounds that may be of concern and the enormous expenses (in terms of time, money, and animals) associated with rodent mutagenicity bioassays, this endpoint is a major target for the development of alternative approaches for screening and prediction. The majority of old-aged expert systems and quantitative structure-activity relationship (QSAR) models may show reduced performance over time for their application on newer chemical candidates; thus, researchers constantly try to improve the modeling strategies. In our report, we initially performed traditional classification-based linear discriminant analysis (LDA) QSAR modeling using the benchmark Ames dataset of diverse chemicals (6512 compounds) to recognize the relationship between the molecules and their potential mutagenic behavior. The classical LDA QSAR model is developed from a selected set of 2D descriptors. The LDA QSAR model was developed by using a total of 31 descriptors identified from the analysis of the most discriminating features. Additionally, we have used similarity-derived features obtained from the read-across (RA) to develop an RA-based QSAR model. The developed RA-based LDA QSAR model has better predictivity, transferability, and interpretability compared to the LDA QSAR model, and it uses a very small number of descriptors compared to the classical QSAR model. Different machine learning (ML) models were also developed using the descriptors appearing in the read-across-based LDA QSAR model for comparative studies. We have checked the prediction quality of 216 true external set compounds using the novel similarity-derived RA model. The performance of the OECD toolbox is also compared with the RA-derived LDA QSAR model for a true external set. The current study aimed to explore the significance of the read-across-based algorithm and its application to the most current experimental mutagenicity data to complement already available expert systems.


Improvement of the fatigue resistance of NiTi endodontic files by surface and bulk modifications.
To assess the failure mechanism of rotary NiTi instruments by chemical, structural and morphological analyses to provide a rational explanation of the effects of surface and bulk treatments on their resistance to fatigue fracture. Thermal treatment (350-500 °C) was performed on electropolished (EP) and non-electropolished (Non-EP) NiTi endodontic instruments. Bulk and surface chemical composition and crystallographic structures were determined by energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD) to evaluate the effects of thermal treatment and electropolishing on the NiTi alloy. Fatigue tests of all instruments were performed. Surface morphology before and after the tests, and fractured section were analysed using scanning electron microscopy to determine crack extensions. Results were analysed statistically using analysis of variance (anova) and post hoc Student-Newman-Keuls test. Before thermal treatment, significant differences (P < 0.05) in fatigue resistance between EP and Non-EP instruments (the number of revolutions to failure, N(f) , was 385 and 160, respectively) were attributed to differences in the surface morphology of the instruments. SEM analysis of the fracture surfaces indicated that flexural fatigue fractures occurred in two steps: first by a slow growth of initial cracks and then rapid rupture of the remaining material. Thermal treatment did not affect the surface morphology but resulted in significant changes in the instrument bulk with the appearance of an R-phase and an improved fatigue resistance; indeed after treatment at 500 °C, N(f) increased up to 829 and 474 for EP and Non-EP instruments, respectively. Both thermal treatment and electropolishing improved the resistance of NiTi rotary instruments against fatigue fracture.


Efficacy of the Da Vinci surgical system in abdominal surgery compared with that of laparoscopy: a systematic review and meta-analysis.
The main aim of this review was to compare the safety and efficacy of the Da Vinci Surgical System (DVSS) and conventional laparoscopic surgery (CLS) in different types of abdominal intervention. DVSS is an emerging laparoscopic technology. The surgeon directs the robotic arms of the system through a console by means of hand controls and pedals, making use of a stereoscopic viewing system. DVSS is currently being used in general, urological, gynecologic, and cardiothoracic surgery. This systematic review analyses the best scientific evidence available regarding the safety and efficacy of DVSS in abdominal surgery. The results found were subjected to meta-analysis whenever possible. Thirty-one studies, 6 of them randomized control trials, involving 2166 patients that compared DVSS and CLS were examined. The procedures undertaken were fundoplication (9 studies, one also examining cholecystectomy), Heller myotomy (3 studies), gastric bypass (4), gastrectomy (2), bariatric surgery (1), cholecystectomy (4), splenectomy (1), colorectal resection (7), and rectopexy (1). DVSS was found to be associated with fewer Heller myotomy-related perforations, a more rapid intestinal recovery time after gastrectomy-and therefore a shorter hospital stay, a shorter hospital stay following cholecystectomy (although the duration of surgery was longer), longer colorectal resection surgery times, and a larger number of conversions to open surgery during gastric bypass. The publications reviewed revealed DVSS to offer certain advantages with respect to Heller myotomy, gastrectomy, and cholecystectomy. However, these results should be interpreted with caution until randomized clinical trials are performed and, with respect to oncologic indications, studies include variables such as survival.


Three dimensional ultrasound diagnosis of caudal regression syndrome at 14 gestational weeks.
Caudal regression syndrome (CRS) is a rare complex abnormality, characterized by agenesis of the sacrum and lumbar spine, with lower limb neurological deficit and accompanying deformities of the pelvis, lower extremities, genitourinary, gastrointestinal and cardiac systems. Pregnancies complicated by insulin treated diabetes carry higher risk of fetal CRS than non-diabetic pregnancies. Three dimensional (3D) and four dimensional (4D) ultrasound may assist in early detection of CRS. We report a case of CRS diagnosed by 3D and 4D ultrasound examination at 14 weeks of gestation in a diabetic patient.


Abnormal esophageal body function: radiographic-manometric correlation.
Stationary manometry is the gold standard for the evaluation of patients with suspected esophageal motility disorders. Comparison of videoesophagram in the evaluation of esophageal motility disorders with stationary motility has not been objectively studied. Two hundred two patients with foregut symptoms underwent stationary motility and videoesophagram. Radiographic assessment of esophageal motility was done by video recording of five 10-cc swallows of barium. Abnormal esophageal body function was defined by stasis of barium in the middle third of the esophagus on at least four swallows or stasis on at least three swallows in the distal third. Stationary manometry was performed using a five-channel water perfused system. Contraction amplitudes <25 mm Hg in any of the last two channels or the presence of simultaneous or interrupted waves in 10 per cent or more were considered to be abnormal. Sixty-two patients had abnormal manometry. Thirty-four patients also demonstrated abnormal videoesophagrams for an overall sensitivity of 55 per cent. The positive predictive value was 53 per cent; specificity was 79 per cent; and negative predictive value was 80 per cent. Sensitivity was greatest in patients with achalasia (94%) and scleroderma (100%) and in patients presenting with dysphagia (89%). Sensitivity was poor for nonspecific esophageal motility disorders. A videoesophagram is relatively insensitive in detecting motility disorders. It seems most useful in the detection of patients with esophageal dysfunction, for which surgical treatment is beneficial, and in those patients presenting with dysphagia.


Emotional hyper-reactivity in borderline personality disorder is related to trauma and interpersonal themes.
Heightened emotional reactivity is one of the core features of borderline personality disorder (BPD). However, recent findings could not provide evidence for a general emotional hyper-reactivity in BPD. The present study examines the emotional responding to self-relevant pictures in dependency of the thematic category (e.g., trauma, interpersonal interaction) in patients with BPD. Therefore, women with BPD (n=31), women with major depression disorder (n=29) and female healthy controls (n=33) rated pictures allocated to thematically different categories (violence, sexual abuse, interaction, non-suicidal self-injury, and suicide) regarding self-relevance, arousal, valence and the urge of non-suicidal self-injury. Compared to both control groups, patients with BPD reported higher self-relevance regarding all categories, but significantly higher emotional ratings only for pictures showing sexual abuse and interpersonal themes. In addition, patients with BPD and comorbid posttraumatic stress disorder showed higher emotional reactivity in violence pictures. Our data provide clear evidence that patients with BPD show a specific emotional hyper-reactivity with respect to schema-related triggers like trauma and interpersonal situations. Future studies are needed to investigate physiological responses to these self-relevant themes in patients with BPD.


Global and endothelial G-protein coupled receptor 75 (GPR75) knockout relaxes pulmonary artery and mitigates hypoxia-induced pulmonary hypertension.
Pulmonary hypertension (PH) is a multifactorial disease with a poor prognosis and inadequate treatment options. We found two-fold higher expression of the orphan G-Protein Coupled Receptor 75 (GPR75) in leukocytes and pulmonary arterial smooth muscle cells from idiopathic PH patients and from lungs of C57BL/6 mice exposed to hypoxia. We therefore postulated that GPR75 signaling is critical to the pathogenesis of PH. To test this hypothesis, we exposed global (Gpr75-/-) and endothelial cell (EC) GPR75 knockout (EC-Gpr75-/-) mice and wild-type (control) mice to hypoxia (10% oxygen) or normal atmospheric oxygen for 5 weeks. We then recorded echocardiograms and performed right heart catheterizations. Chronic hypoxia increased right ventricular systolic and diastolic pressures in wild-type mice but not Gpr75-/- or EC-Gpr75-/- mice. In situ hybridization and qPCR results revealed that Gpr75 expression was increased in the alveoli, airways and pulmonary arteries of mice exposed to hypoxia. In addition, levels of chemokine (CC motif) ligand 5 (CCL5), a low affinity ligand of GPR75, were increased in the lungs of wild-type, but not Gpr75-/-, mice exposed to hypoxia, and CCL5 enhanced hypoxia-induced contraction of intra-lobar pulmonary arteries in a GPR75-dependent manner. Gpr75 knockout also increased pulmonary cAMP levels and decreased contraction of intra-lobar pulmonary arteries evoked by endothelin-1 or U46619 in cAMP-protein kinase A-dependent manner. These results suggest GPR75 has a significant role in the development of hypoxia-induced PH.


Variations in Soil Bacterial Community Diversity and Structures Among Different Revegetation Types in the Baishilazi Nature Reserve.
We compared patterns of soil bacterial community diversity and structure in six secondary forests (JM, Juglans mandshurica; QM, Quercus mongolica; MB, mixed Broadleaf forest; BE, Betula ermanii; CB, conifer-broadleaf forest; PT, Pinus tabuliformis) and two plantation forests (LG, Larix gmelinii; PK, Pinus koraiensis) of the Baishilazi Nature Reserve, China, based on the 16S rRNA high-throughput Illumina sequencing data. The correlations between the bacterial community and soil environmental factors were also examined. The results showed that the broadleaf forests (JM, QM, MB) had higher levels of total C (TC), total N (TN), available N (AN), and available K (AK) compared to the coniferous forests (PT, LG, PK) and conifer-broadleaf forest (CB). Different revegetation pathways had different effects on the soil bacterial community diversity and structure. For the α-diversity, the highest Shannon index and Simpson index were found in JM. The Simpson index was significantly positively correlated with the available P (AP) (P < 0.05), and the Shannon index was significantly positively correlated with AK (P < 0.05). Compared with others, the increased ACE index and Chao1 index were observed in the CB and MB, and both of these α-diversity were significantly negative with AK (P < 0.05). The relative abundances of bacterial phyla and genera differed among different revegetation types. At the phylum level, the dominant phylum groups in all soils were Proteobacteria, Acidobacteria, Actinobacteria, Verrucomicrobia, Chloroflexi, Bacteroidetes, Gemmatimonadetes, and Planctomycetes. Significant differences in relative abundance of bacteria phyla were found for Acidobacteria, Actinobacteria, Chloroflexi, Gemmatimonadetes, and Proteobacteria. Correlation analysis showed that Soil pH, TC, TN, AP, and AK were the main abiotic factors structuring the bacterial communities. As revealed by the clear differentiation of bacterial communities and the clustering in the heatmap and in the PCA plots, broadleaf forests and coniferous forests harbored distinct bacterial communities, indicating a significant impact of the respective reforestation pathway on soil bacterial communities in the Baishilazi Nature Reserve.


Host-parasite coevolution and patterns of adaptation across time and space.
The description of coevolutionary dynamics requires a characterization of the evolutionary dynamics of both the parasite and its host. However, a thorough description of the underlying genetics of the coevolutionary process is often extremely difficult to carry out. We propose that measures of adaptation (mean population fitness) across time or space may represent a feasible alternative approach for characterizing important features of the coevolutionary process. We discuss recent experimental work in the light of simple mathematical models of coevolution to demonstrate the potential power of this phenotypic experimental approach.


Potent kinetic stabilizers that prevent transthyretin-mediated cardiomyocyte proteotoxicity.
A valine-to-isoleucine mutation at position 122 of the serum protein transthyretin (TTR), found in 3 to 4% of African Americans, alters its stability, leading to amyloidogenesis and cardiomyopathy. In addition, 10 to 15% of individuals older than 65 years develop senile systemic amyloidosis and cardiac TTR deposits because of wild-type TTR amyloidogenesis. Although several drugs are in development, no approved therapies for TTR amyloid cardiomyopathy are yet available, so the identification of additional compounds that prevent amyloid-mediated cardiotoxicity is needed. To this aim, we developed a fluorescence polarization-based high-throughput screen and used it to identify several new chemical scaffolds that target TTR. These compounds were potent kinetic stabilizers of TTR and prevented TTR tetramer dissociation, partial unfolding, and aggregation of both wild type and the most common cardiomyopathy-associated TTR mutant, V122I-TTR. High-resolution co-crystal structures and characterization of the binding energetics revealed how these diverse structures bound to tetrameric TTR. These compounds effectively inhibited the proteotoxicity of V122I-TTR toward human cardiomyocytes. Several of these ligands stabilized TTR in human serum more effectively than diflunisal, which is a well-studied inhibitor of TTR aggregation, and may be promising leads for the treatment or prevention of TTR-mediated cardiomyopathy.


Noise-immune cavity-enhanced optical frequency comb spectroscopy.
We present a new method of optical frequency comb spectroscopy that combines cavity enhancement with frequency modulation to obtain immunity to laser frequency-to-amplitude noise conversion by the cavity modes and, thus, high absorption sensitivity over a broad spectral range. A frequency comb is locked to a cavity with a free spectral range (FSR) equal to 4/3 times the repetition rate of the laser, and phase-modulated at a frequency equal to the cavity FSR. The transmitted light is analyzed by a Fourier transform spectrometer with a high bandwidth detector. Phase-sensitive detection of the interferogram yields a noise-immune cavity-enhanced optical frequency comb spectroscopy (NICE-OFCS) signal. In the first demonstration, we record NICE-OFCS signals from the overtone CO2 band at 1575 nm with absorption sensitivity of 4.3×10(-10) cm(-1) Hz(-1/2) per spectral element, close to the shot noise limit.


A novel re-attachable stereotactic frame for MRI-guided neuronavigation and its validation in a large animal and human cadaver model.
Stereotactic frame systems are the gold-standard for stereotactic surgeries, such as implantation of deep brain stimulation (DBS) devices for treatment of medically resistant neurologic and psychiatric disorders. However, frame-based systems require that the patient is awake with a stereotactic frame affixed to their head for the duration of the surgical planning and implantation of the DBS electrodes. While frameless systems are increasingly available, a reusable re-attachable frame system provides unique benefits. As such, we created a novel reusable MRI-compatible stereotactic frame system that maintains clinical accuracy through the detachment and reattachment of its stereotactic devices used for MRI-guided neuronavigation. We designed a reusable arc-centered frame system that includes MRI-compatible anchoring skull screws for detachment and re-attachment of its stereotactic devices. We validated the stability and accuracy of our system through phantom, in vivo mock-human porcine DBS-model and human cadaver testing. Phantom testing achieved a root mean square error (RMSE) of 0.94 ± 0.23 mm between the ground truth and the frame-targeted coordinates; and achieved an RMSE of 1.11 ± 0.40 mm and 1.33 ± 0.38 mm between the ground truth and the CT- and MRI-targeted coordinates, respectively. In vivo and cadaver testing achieved a combined 3D Euclidean localization error of 1.85 ± 0.36 mm (p < 0.03) between the pre-operative MRI-guided placement and the post-operative CT-guided confirmation of the DBS electrode. Our system demonstrated consistent clinical accuracy that is comparable to conventional frame and frameless stereotactic systems. Our frame system is the first to demonstrate accurate relocation of stereotactic frame devices during in vivo MRI-guided DBS surgical procedures. As such, this reusable and re-attachable MRI-compatible system is expected to enable more complex, chronic neuromodulation experiments, and lead to a clinically available re-attachable frame that is expected to decrease patient discomfort and costs of DBS surgery.


The Role of Fatty Acid Signaling in Islet Beta-Cell Adaptation to Normal Pregnancy.
Maintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated. To determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS). Age matched virgin, early pregnant (gestational day-11, G11) and late pregnant (G19) Sprague-Dawley rats were studied. Fasted and fed state biochemistry, oral glucose tolerance tests (OGTT), and fasted and post-OGTT liver glycogen, were determined to assess in vivo metabolic characteristics. In isolated islets, FA (BSA-bound palmitate 0.25 mmol/l) augmentation of GSIS, FA partitioning into esterification and oxidation processes using metabolic tracer techniques, lipolysis by glycerol release, triacylglycerols (TG) content, and the expression of key beta-cell genes were determined. Plasma glucose in pregnancy was lower, including during the OGTT (glucose area under the curve 0-120 min (AUC0-120); 655±24 versus 849±13 mmol.l-1.min; G19 vs virgin; P<0.0001), with plasma insulin concentrations equivalent to those of virgin rats (insulin AUC0-120; 97±7 versus 83±7 ng.ml-1.min; G19 vs virgin; not significant). Liver glycogen was depleted in fasted G19 rats with full recovery after oral glucose. Serum TG increased during pregnancy (4.4±0.4, 6.7±0.5; 17.1±1.5 mmol/l; virgin, G11, G19, P<0.0001), and islet TG content decreased (147±42, 172±27, 73±13 ng/µg protein; virgin, G11, G19; P<0.01). GSIS in isolated islets was increased in G19 compared to virgin rats, and this effect was augmented in the presence of FA. FA esterification into phospholipids, monoacylglycerols and TG were increased, whereas FA oxidation was reduced, in islets of pregnant compared to virgin rats, with variable effects on lipolysis dependent on gestational age. Expression of Ppargc1a, a key regulator of mitochondrial metabolism, was reduced by 51% in G11 and 64% in G19 pregnant rat islets compared to virgin rat islets (P<0.001). A lowered set-point for islet and hepatic glucose homeostasis in the pregnant rat has been confirmed. Islet adaptation to pregnancy includes increased FA esterification, reduced FA oxidation, and enhanced FA augmentation of glucose-stimulated insulin secretion.


Organic compounds in circumstellar and interstellar environments.
Recent research has discovered that complex organic matter is prevalent throughout the Universe. In the Solar System, it is found in meteorites, comets, interplanetary dust particles, and planetary satellites. Spectroscopic signatures of organics with aromatic/aliphatic structures are also found in stellar ejecta, diffuse interstellar medium, and external galaxies. From space infrared spectroscopic observations, we have found that complex organics can be synthesized in the late stages of stellar evolution. Shortly after the nuclear synthesis of the element carbon, organic gas-phase molecules are formed in the stellar winds, which later condense into solid organic particles. This organic synthesis occurs over very short time scales of about a thousand years. In order to determine the chemical structures of these stellar organics, comparisons are made with particles produced in the laboratory. Using the technique of chemical vapor deposition, artificial organic particles have been created by injecting energy into gas-phase hydrocarbon molecules. These comparisons led us to believe that the stellar organics are best described as amorphous carbonaceous nanoparticles with mixed aromatic and aliphatic components. The chemical structures of the stellar organics show strong similarity to the insoluble organic matter found in meteorites. Isotopic analysis of meteorites and interplanetary dust collected in the upper atmospheres have revealed the presence of pre-solar grains similar to those formed in old stars. This provides a direct link between star dust and the Solar System and raises the possibility that the early Solar System was chemically enriched by stellar ejecta with the potential of influencing the origin of life on Earth.


Value-based decision-making predicts alcohol use and related problems in young men.
Alcohol consumption is a leading cause of morbidity and mortality worldwide, disproportionately affecting young men. Heavy episodic drinking is particularly prevalent among men, with this behavior peaking between the ages of 20 and 24. We sought to identify dimensions of decision-making in men that would predict the development of hazardous alcohol use through emerging adulthood. This prospective observational study profiled value-based decision-making in 198 healthy men at age 18 and assessed their alcohol involvement annually until age 24. Latent growth curve modeling estimated individual variability in trajectories of alcohol involvement and regressed this variability on five choice dimensions. Low loss aversion predicted sustained heavy episodic drinking from age 18 to 24. Both high delay discounting and risk-seeking for gains independently predicted a considerably higher cumulative alcohol use during these 6 years, with high delay discounting indicating escalating consumption from age 21. Risk-seeking for gains additionally predicted meeting more criteria for Alcohol Use Disorder in these 6 years. Risk-seeking for losses was not significantly related to alcohol outcomes. Choice preferences were largely independent of each other but were correlated with choice consistency, with low consistency predicting heavy episodic drinking from age 18 to 24 beyond these associations. The predictive effects collectively suggest that overvaluing immediate and probabilistic incentives, rather than underestimating harm, drives hazardous drinking in young men. The differential relations of choice preferences and consistency to alcohol involvement through emerging adulthood provide distinct cognitive-behavioral patterns that warrant consideration in the development of harm reduction interventions.


Implementing social justice in the transition from illicit to legal cannabis.
Background: The legalization of cannabis for adult use is being increasingly embraced in several countries and local entities. A driving force for these changes has been the individual, family, community, societal, and economic costs of cannabis prohibition, which have fallen most heavily upon disadvantaged minority populations.Objectives: In this review, we explore whether the legalization of cannabis has begun to correct the injustices of cannabis prohibition. Progress is assessed in five areas of social justice related to cannabis prohibition: expungement of previous arrests and convictions for cannabis-related crimes that are no longer illegal; consequences of cannabis-related offenses in a cannabis-legal environment; diversity of the cannabis-legal industry; funding of equity and/or restorative justice programs for those communities most affected by cannabis prohibition; and risks of cannabis legalization negatively impacting the populations that most suffered under the legacy of cannabis prohibition.Methods: Iterative and focused review.Results: There has been some progress in expunging previous cannabis-related convictions, particularly misdemeanors, and decreasing cannabis-related arrests. Encouraging diversity in the cannabis industry and the funding of equity programs has been very limited. There is no evidence to-date that populations that have suffered most as a result of cannabis prohibition are at increased risk from its legalization.Conclusions: Focused regulatory efforts and financial resources (from both cannabis revenue and savings from the abolition of cannabis prohibition) as well as more attentive data collection and analysis should be utilized to assure that all individuals experience the benefits, and avoid the consequences, of cannabis legalization.


Possible mechanisms of bleomycin-induced fibrosis.
Bleomycin-induced fibrosis is probably the composition of several mechanisms working in sequence and simultaneously. The role(s) and interaction of the cellular, biochemical, and molecular elements of bleomycin-induced fibrosis are examined.


Post-encystment/established immunity in cystic echinococcosis: is it really that simple?
In 1982, Rickard & Williams stated that immunity to larval taeniid cestodes could be divided into two different phases: the establishment phase, operating against oncospheres, and the established phase, operating against established metacestodes in the tissues. These concepts were largely based on experimental and veterinary data. As a result of subsequent research combined with clinical data, we can consider that, for metacestodes of Echinococcus spp, a single established phase is probably too simple a concept. These parasites show developmental changes in different hosts over time, the most significant being growth, fertility and degeneration. Recent clinical cyst classifications (WHO/IWGE) have highlighted that all hydatid cysts are morphologically not the same. This is important for treatment but fails to completely address variation in the host/parasite response and the understanding of parasite survival. This review attempts to relate the immunological and developmental data obtained from experimental, veterinary and medical studies to update our understanding of established immunity against E. granulosus. It proposes that a single 'Established' phase for E. granulosus could be subdivided into four additional phases: maturing; stable; unstable and degenerative. Combining this type of information with existing cyst classification systems could significantly benefit our understanding of the parasites immunobiology.


Working memory load modulates distractor competition in primary visual cortex.
When stimuli compete for sensory processing and response selection, coherent goal-guided behavior requires cognitive control so that task-relevant "targets" rather than irrelevant distractors are selected. It has been shown that reduced cognitive control under high working memory load increases distractor competition for selection. It remains unknown, though, whether cognitive control by working memory has an effect on the earliest levels of sensory processing in primary visual cortex. The present study addressed this question by having subjects perform a selective attention task involving classification of meaningful target objects while also ignoring congruent and incongruent distractor images. The level of cognitive control over distractor competition was varied through a concurrent working memory task of either low (1 digit) or high (6 digits) load. Functional magnetic resonance imaging revealed greater distractor competition effects not only on behavior but also on the sensory correlates in primary visual cortex (areas V1-V2) in conditions of high (vs. low) working memory load. In addition, high working memory load resulted in increased congruency-related functional connectivity between anterior cingulate cortex and V1. These results are the first to establish the neural correlates of distractor competition effects in primary visual cortex and the critical role of working memory in their cognitive control.


Anatomical Wrist Patterns on Plain Radiographs.
Interpreting the structure in the wrist is complicated by the existence of multiple joints as well as variability in bone shapes and anatomical patterns. Previous studies have evaluated lunate and capitate shape in an attempt to understand functional anatomical patterns. The purpose of this study was to describe anatomical shapes and wrist patterns in normal wrist radiographs. We hypothesized that there is a significant relationship in the midcarpal joint with at least one consistent pattern of wrist anatomy. Seventy plain posteroanterior (PA) and lateral wrist radiographs were evaluated. These radiographs were part of a previously established normal database, had all been read by a radiologist as normal, and had undergone further examination by 2 hand surgeons for quality. Evaluation included: lunate and capitate shape (type 1 and 2 lunate shape according to the classification system by Viegas et al.), ulnar variance, radial inclination and height, and volar tilt. A significant association was found between lunate and capitate shape using a dichotomal classification system for both lunate and capitate shapes (p=0.003). Type 1 wrists were defined as lunate type1and a spherical distal capitate. Type 2 wrists had a lunate type 2 and a flat distal capitate. No statistically significant associations were detected between these wrist types and measurements of the radiocarpal joint. There was a significant relationship between the bone shapes within the midcarpal joint. These were not related to radiocarpal anatomical shape. Further study is necessary to better describe the two types of wrist patterns that were defined and to understand their influence on wrist biomechanics and pathology.


Mycobacterial infections in AIDS.
Tuberculosis (TB) remains uniquely important among acquired immune deficiency syndrome (AIDS)-associated opportunistic infections: it presents the greatest public health hazard worldwide, is the most readily curable, and is largely preventable with existing means. Given the expanding pool of human immunodeficiency virus (HIV) seropositive persons, particularly in developing nations where Mycobacterium tuberculosis remains a leading health problem, one can expect a continued rise in TB cases during the 1990s. Global efforts to eliminate TB are now inextricably entwined with the effectiveness of measures to curtail the HIV epidemic. Mycobacterium avium complex infection, currently an intractable late complication of aids, may increase in clinical importance as success in managing other opportunistic infections and HIV disease itself improves. Understanding of the pathogenesis and management of mycobacterial diseases should increase rapidly given the renewed research spurred on by the advent of HIV.


New method for detecting cellular transforming genes.
Tumor induction in athymic nude mice can be used to detect dominant transforming genes in cellular DNA. Mouse NIH 3T3 cells freshly transfected with either cloned Moloney sarcoma proviral DNA or cellular DNA's derived from virally transformed cells induced tumors when injected into athymic nu/nu mice. Tumors were also induced by cells transfected with DNA from two tumor-derived and one chemically transformed human cell lines. The mouse tumors induced by human cell line DNA's contained human DNA sequences, and DNA derived from these tumors was capable of inducing both tumors and foci on subsequent transfection. Tumor induction in nude mice represents a useful new method for the detection and selection of cells transformed by cellular oncogenes.


Enhancing team-sport athlete performance: is altitude training relevant?
Field-based team sport matches are composed of short, high-intensity efforts, interspersed with intervals of rest or submaximal exercise, repeated over a period of 60-120 minutes. Matches may also be played at moderate altitude where the lower oxygen partial pressure exerts a detrimental effect on performance. To enhance run-based performance, team-sport athletes use varied training strategies focusing on different aspects of team-sport physiology, including aerobic, sprint, repeated-sprint and resistance training. Interestingly, 'altitude' training (i.e. living and/or training in O(2)-reduced environments) has only been empirically employed by athletes and coaches to improve the basic characteristics of speed and endurance necessary to excel in team sports. Hypoxia, as an additional stimulus to training, is typically used by endurance athletes to enhance performance at sea level and to prepare for competition at altitude. Several approaches have evolved in the last few decades, which are known to enhance aerobic power and, thus, endurance performance. Altitude training can also promote an increased anaerobic fitness, and may enhance sprint capacity. Therefore, altitude training may confer potentially-beneficial adaptations to team-sport athletes, which have been overlooked in contemporary sport physiology research. Here, we review the current knowledge on the established benefits of altitude training on physiological systems relevant to team-sport performance, and conclude that current evidence supports implementation of altitude training modalities to enhance match physical performances at both sea level and altitude. We hope that this will guide the practice of many athletes and stimulate future research to better refine training programmes.


Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.
Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model.


Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder.
Alterations of microbiota-gut-brain axis have been invoked in the pathogenesis of autism spectrum disorders (ASD). Mouse models could represent an excellent tool to understand how gut dysbiosis and related alterations may contribute to autistic phenotype. In this study we paralleled gut microbiota (GM) profiles, behavioral characteristics, intestinal integrity and immunological features of colon tissues in BTBR T + tf/J (BTBR) inbred mice, a well established animal model of ASD. Sex differences, up to date poorly investigated in animal models, were specifically addressed. Results showed that BTBR mice of both sexes presented a marked intestinal dysbiosis, alterations of behavior, gut permeability and immunological state with respect to prosocial C57BL/6j (C57) strain. Noticeably, sex-related differences were clearly detected. We identified Bacteroides, Parabacteroides, Sutterella, Dehalobacterium and Oscillospira genera as key drivers of sex-specific gut microbiota profiles associated with selected pathological traits. Taken together, our findings indicate that alteration of GM in BTBR mice shows relevant sex-associated differences and supports the use of BTBR mouse model to dissect autism associated microbiota-gut-brain axis alteration.


Risk of serious falls associated with oxybutynin and tolterodine: a population based study.
We compared the short-term risk of falls among recipients of oxybutynin or tolterodine to treat urinary incontinence. We conducted a population based, retrospective cohort study with propensity score matching among patients 66 years old or older who commenced treatment with oxybutynin or tolterodine in Ontario, Canada. The primary outcome was a hospital visit for a fall within 90 days of drug initiation. Secondary outcomes included hospital visits for fractures, delirium or all cause mortality. We found no difference in the risk of falls among users of oxybutynin vs tolterodine (adjusted hazard ratio 1.04, 95% CI 0.95 to 1.14). Secondary analyses revealed no differential risk of fractures (aHR 0.96, 95% CI 0.82 to 1.13) or delirium (aHR 0.90, 95% CI 0.66 to 1.23) associated with oxybutynin. However, statistically significant increases in the risk of all cause hospitalization (aHR 1.12, 95% CI 1.07 to 1.17) and death (aHR 1.20, 95% CI 1.07 to 1.35) were seen with oxybutynin. Oxybutynin was not associated with a short-term increased risk of hospital visit for falls, fractures or delirium compared to tolterodine. Further research is needed to confirm whether oxybutynin is associated with an increased risk of hospitalization or death.


InGaZnO semiconductor thin film fabricated using pulsed laser deposition.
The InGaZnO thin films are fabricated on the quartz glass using pulsed laser deposition (PLD), where the target is prepared by mixing the Ga(2)O(3), In(2)O(3), and ZnO powders at a mol ratio of 1:1:8 before the solid-state reactions in a tube furnace at the atmospheric pressure. The product thin films were characterized comprehensively by X-ray diffraction, atomic force microscopy, Hall-effect investigation, and X-ray photoelectron spectroscopy. Thus, we demonstrate semiconductor thin-film materials with high smoothness, high transmittance in visible region, and excellent electrical properties.


Electrophysiological correlates of similarity-based interference during detection of visual forms.
Illusory figure completion demonstrates the ability of the visual system to integrate information across gaps. Mechanisms that underlie figural emergence support the interpolation of contours and the filling-in of form information [Grossberg, S., & Mingolla, E. Neural dynamics of form perception: Boundary completion, illusory figures and neon colour spreading. Psychological Review, 92, 173-211, 1985]. Although both processes contribute to figure formation, visual search for an illusory target configuration has been shown to be susceptible to interfering form, but not contour, information [Conci, M., Müller, H. J., & Elliott, M. A. The contrasting impact of global and local object attributes on Kanizsa figure detection. Submitted]. Here, the physiological basis of form interference was investigated by recording event-related potentials elicited from contour- and surface-based distracter interactions with detection of a target Kanizsa figure. The results replicated the finding of form interference and revealed selection of the target and successful suppression of the irrelevant distracter to be reflected by amplitude differences in the N2pc component (240-340 msec). In conclusion, the observed component variations reflect processes of target selection on the basis of integrated form information resulting from figural completion processes.