Parenting Through Academia as a SICB Member.
The Society for Integrative and Comparative Biology (SICB) has made tremendous improvements to their annual meeting in an effort to promote inclusivity, diversity, and accessibility to all scientists. However, within academia as an institution overall, many scientists face personal challenges that directly compete with the rigorous culture considered a requirement for success as an academic. Among these challenges is balancing parenthood with academic responsibilities, such as conference attendance and productivity. Herein, we present a report of the survey administered to the members of SICB and from discussion held during the Parenting through Academia workshop at the 2020 annual meeting. We hope that this information brings to the Society an opportunity for open collegial discussion, mentorship, and community building, and sheds light on new strategies that could be undertaken to support not only parents, but SICB membership as a whole.


Evaluating international research ethics capacity development: an empirical approach.
The US national institutes of health, Fogarty International Center (NIH-FIC) has, for the past 13 years, been a leading funder of international research ethics education for resource-limited settings. Nearly half of the NIH-FIC funding in this area has gone to training programs that train individuals from sub-Saharan Africa. Identifying the impact of training investments, as well as the potential predictors of post-training success, can support curricular decisionmaking, help establish funding priorities, and recognize the ultimate outcomes of trainees and training programs. Comprehensive evaluation frameworks and targeted evaluation tools for bioethics training programs generally, and for international research ethics programs in particular, are largely absent from published literature. This paper shares an original conceptual framework, data collection tool, and detailed methods for evaluating the inputs, processes, outputs, and outcomes of research ethics training programs serving individuals in resource-limited settings. This paper is part of a collection of papers analyzing the Fogarty International Center's International Research Ethics Education and Curriculum Development program.


Goal-Directed Fluid Therapy Does Not Improve Early Glomerular Filtration Rate in a Porcine Renal Transplantation Model.
Insufficient fluid administration intra- and postoperatively may lead to delayed renal graft function (DGF), while fluid overload increases the risk of heart failure, infection, and obstipation. Several different fluid protocols have been suggested to ensure optimal fluid state. However, there is a lack of evidence of the clinical impact of these regimens. This study aimed to determine whether individualized goal-directed fluid therapy (IGDT) positively affects the initial renal function compared to a high-volume fluid therapy (HVFT) and to examine the effects on renal endothelial glycocalyx, inflammatory and oxidative stress markers, and medullary tissue oxygenation. The hypothesis was that IGDT improves early glomerular filtration rate (GFR) in pigs subjected to renal transplantation. This was an experimental randomized study. Using a porcine renal transplantation model, animals were randomly assigned to receive IGDT or HVFT during and until 1 hour after transplantation from brain-dead donors. The kidneys were exposed to 18 hours of cold ischemia. The recipients were observed until 10 hours after reperfusion, which included GFR measured as clearance of chrom-51-ethylendiamintetraacetat (Cr-EDTA), animal weight, and renal tissue oxygenation by fiber optic probes. The renal expression of inflammatory and oxidative stress markers as well as glomerular endothelial glycocalyx were analyzed in the graft using polymerase chain reaction (PCR) technique and immunofluorescence. Twenty-eight recipient pigs were included for analysis. We found no evidence that IGDT improved early GFR compared to HVFT (P = .45), while animal weight increased more in the HVFT group (a mean difference of 3.4 kg [1.96-4.90]; P < .0001). A better, however nonsignificant, preservation of glomerular glycocalyx (P = .098) and significantly lower levels of the inflammatory marker cyclooxygenase 2 (COX-2) was observed in the IGDT group when compared to HVFT. COX-2 was 1.94 (1.50-2.39; P = .012) times greater in the HVFT group when compared to the IGDT group. No differences were observed in outer medullary tissue oxygenation or oxidative stress markers. IGDT did not improve early GFR; however, it may reduce tissue inflammation and could possibly lead to preservation of the glycocalyx compared to HVFT.


Recent Anthropogenic Plant Extinctions Differ in Biodiversity Hotspots and Coldspots.
During the Anthropocene, humans are changing the Earth system in ways that will be detectable for millennia to come [1]. Biologically, these changes include habitat destruction, biotic homogenization, increased species invasions, and accelerated extinctions [2]. Contemporary extinction rates far surpass background rates [3], but they seem remarkably low in plants [4, 5]. However, biodiversity is not evenly distributed, and as a result, extinction rates may vary among regions. Some authors have contentiously argued that novel anthropic habitats and human-induced plant speciation can actually increase regional biodiversity [6, 7]. Here, we report on one of the most comprehensive datasets to date, including regional and global plant extinctions in both biodiversity hotspots (mostly from Mediterranean-type climate regions) and coldspots (mostly from Eurasian countries). Our data come from regions covering 15.3% of the Earth's surface and span over 300 years. With this dataset, we explore the trends, causes, and temporal dynamics of recent plant extinctions. We found more, and faster accrual of, absolute numbers of extinction events in biodiversity hotspots compared to coldspots. Extinction rates were also substantially higher than historical background rates, but recent declines are evident. We found higher levels of taxonomic uniqueness being lost in biodiversity coldspots compared to hotspots. Causes of plant extinctions also showed distinct temporal patterns, with agriculture, invasions, and urbanization being significant drivers in hotspots, while hydrological disturbance was an important driver in coldspots. Overall, plant extinctions over the last three centuries appear to be low, with a recent (post-1990) and steady extinction rate of 1.26 extinctions/year.


Impact of high-risk sex and focused interventions in heterosexual HIV epidemics: a systematic review of mathematical models.
The core-group theory of sexually transmitted infections suggests that targeting prevention to high-risk groups (HRG) could be very effective. We aimed to quantify the contribution of heterosexual HRGs and the potential impact of focused interventions to HIV transmission in the wider community. We systematically identified studies published between 1980 and 2011. Studies were included if they used dynamical models of heterosexual HIV transmission, incorporated behavioural heterogeneity in risk, and provided at least one of the following primary estimates in the wider community (a) the population attributable fraction (PAF) of HIV infections due to HRGs, or (b) the number per capita or fraction of HIV infections averted, or change in HIV prevalence/incidence due to focused interventions. Of 267 selected articles, 22 were included. Four studies measured the PAF, and 20 studies measured intervention impact across 265 scenarios. In low-prevalence epidemics (≤5% HIV prevalence), the estimated impact of sex-worker interventions in the absence of risk compensation included: 6-100% infections averted; 0.9-6.2 HIV infections averted per 100,000 adults; 11-94% and 4-47% relative reduction in prevalence and incidence respectively. In high-prevalence epidemics (>5% HIV prevalence), sex-worker interventions were estimated to avert 6.8-40% of HIV infections and up to 564 HIV infections per 100,000 adults, and reduce HIV prevalence and incidence by 13-27% and 2-14% respectively. In both types of epidemics, greater heterogeneity in HIV risk was associated with a larger impact on the fraction of HIV infections averted and relative reduction in HIV incidence. Focused interventions, as estimated by mathematical models, have the potential to reduce HIV transmission in the wider community across low- and high-prevalence regions. However, considerable variability exists in estimated impact, suggesting that a targeted approach to HIV prevention should be tailored to local epidemiological context.


Specificity and prevalence of natural bovine antimannan antibodies.
Immune responses to the carbohydrate components of microorganisms, mediated both by antibodies and by lectins, are an important part of host defense. In the present experiments, the specificity and presence of natural bovine antibodies against mannan, a common fungal antigen, were examined by enzyme-linked immunosorbent assay (ELISA), using Saccharomyces cerevisiae mannan as an antigen. The results showed that all serum samples from animals of three age groups (newborn, calf, and adult) tested contained antimannan antibodies, and the titer of these antibodies increased significantly in adults. However, titers among individual adult cattle differed widely. Inhibition assays showed that yeast mannan was the strongest inhibitor. D-Mannose exhibited only a minor inhibitory effect at high concentrations. This suggests that most of these antibodies recognize an oligosaccharide-based epitope(s) different from those recognized by lectins. Cattle possess three serum C-type lectins (collectins) capable of recognizing mannan in a calcium-dependent manner. Addition of EDTA to the reaction did not reduce antibody binding, suggesting that the binding of these antibodies to mannan was not affected by the presence of collectin. The antibodies purified from either calf or adult serum by mannan-Sepharose affinity chromatography consisted of mainly immunoglobulin G (IgG) and a smaller amount of IgM. IgG1 was shown to be the dominant antimannan IgG isotype by isotype-specific ELISA. Together, these results demonstrate the production of natural antimannan antibodies in cattle in an age-dependent manner. These antibodies might be involved in defending the host against mannan-containing pathogens as a specific line of defense in conjunction with the innate response by lectins.


Conformable ultrasound breast patch for deep tissue scanning and imaging.
Ultrasound is widely used for tissue imaging such as breast cancer diagnosis; however, fundamental challenges limit its integration with wearable technologies, namely, imaging over large-area curvilinear organs. We introduced a wearable, conformable ultrasound breast patch (cUSBr-Patch) that enables standardized and reproducible image acquisition over the entire breast with less reliance on operator training and applied transducer compression. A nature-inspired honeycomb-shaped patch combined with a phased array is guided by an easy-to-operate tracker that provides for large-area, deep scanning, and multiangle breast imaging capability. The in vitro studies and clinical trials reveal that the array using a piezoelectric crystal [Yb/Bi-Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3] (Yb/Bi-PIN-PMN-PT) exhibits a sufficient contrast resolution (~3 dB) and axial/lateral resolutions of 0.25/1.0 mm at 30 mm depth, allowing the observation of small cysts (~0.3 cm) in the breast. This research develops a first-of-its-kind ultrasound technology for breast tissue scanning and imaging that offers a noninvasive method for tracking real-time dynamic changes of soft tissue.


A resource to explore the discovery of rare diseases and their causative genes.
Here, we describe a dataset with information about monogenic, rare diseases with a known genetic background, supplemented with manually extracted provenance for the disease itself and the discovery of the underlying genetic cause. We assembled a collection of 4166 rare monogenic diseases and linked them to 3163 causative genes, annotated with OMIM and Ensembl identifiers and HGNC symbols. The PubMed identifiers of the scientific publications, which for the first time described the rare diseases, and the publications, which found the genes causing the diseases were added using information from OMIM, PubMed, Wikipedia, whonamedit.com, and Google Scholar. The data are available under CC0 license as spreadsheet and as RDF in a semantic model modified from DisGeNET, and was added to Wikidata. This dataset relies on publicly available data and publications with a PubMed identifier, but by our effort to make the data interoperable and linked, we can now analyse this data. Our analysis revealed the timeline of rare disease and causative gene discovery and links them to developments in methods.


Shape from specularities: computation and psychophysics.
Images of artificial and natural scenes typically contain many 'specularities' generated by mirror-like reflection from glossy surfaces. Until fairly recently computational models of visual processes have tended to regard specularities as obscuring underlying scene structure. Mathematical modelling shows that, on the contrary, they are rich in local geometric information. Recent psychophysical findings support the notion that the brain can apply that information. Our results concern the inference of 3D structure from 2D shaded images of glossy surfaces. Stereoscopically viewed highlights or 'specularities' are found to serve as cues for 3D local surface-geometry.


Overview of cancer incidence and mortality among people living with HIV/AIDS in British Columbia, Canada: Implications for HAART use and NADM development.
The objective of this study is to evaluate the incidence of non-AIDS defining malignancies (NADMs) among people living with HIV/AIDS (PLWHA) in British Columbia, focusing on clinical correlates, highly active antiretroviral therapy (HAART) use, and survival, in order to elucidate mechanisms for NADM development. A retrospective population based analysis was carried out for individuals with HIV/AIDS that began their treatment between 1996 and 2008. There were 145 (2.95%) NADMs and 123 (2.50%) AIDS defining malignancies (ADMs) identified in 4918 PLWHA in the study population. NADMs were represented by a range of cancer types including, most commonly, lung cancer, followed by anal, breast, head/neck, prostate, liver, rectal, and renal cancers. PLWHA had a SIR of 2.05 (CI:1.73, 2.41) for the development of NADMs compared to individuals without an HIV/AIDS diagnosis in the general population. Independent factors significantly associated with a NADM were: male gender, older age, lower CD4 cell counts, previous NADM, absence of HAART (non-HAART versus HAART) and treatment during the early-HAART era (before 2000 versus after 2000). NADMs represent an important source of morbidity for PLWHA. Use of HAART with its associated improvement in immune-restoration, and tailored targeted cancer screening interventions, may be beneficial and improve outcomes in this unique patient population.


Role of the conserved lysine 80 in stabilisation of NF-kappaB p50 DNA binding.
The transcriptional rate of a variety of genes involved in acute-phase response, inflammation, lymphocytic activation, and cell growth or differentiation, is regulated by the DNA binding activity of the inducible transcription factor NF-kappaB. NF-kappaB p50 homodimers bind specifically to DNA, via base and backbone contacts mediated by residues in the flexible loops which link secondary structure elements in both of its two distinct domains. However, it has been suggested that additional contacts which stabilise DNA binding are made by lysine residues located in the C-terminus of the flexible loop which connects A and B beta-sheets of the N-terminal domain of p50. To determine the importance of each of the lysine residues in this region (K77, K79, K80), a series of mutated p50 proteins were generated in which the lysines were changed to alanines. The DNA binding properties of these mutants were analysed by gel electrophoresis DNA binding assays and surface plasmon resonance. This study revealed that the C-terminus of AB loop interacts with DNA through an additional lysine-phosphate backbone ionic bond which makes a significant contribution to the binding energy, thus stabilising the complex. The lysine residue responsible for this interaction is K80 which is conserved in all NF-kappaB/Rel/Dorsal molecules.


A sampling and metagenomic sequencing-based methodology for monitoring antimicrobial resistance in swine herds.
Reliable methods for monitoring antimicrobial resistance (AMR) in livestock and other reservoirs are essential to understand the trends, transmission and importance of agricultural resistance. Quantification of AMR is mostly done using culture-based techniques, but metagenomic read mapping shows promise for quantitative resistance monitoring. We evaluated the ability of: (i) MIC determination for Escherichia coli; (ii) cfu counting of E. coli; (iii) cfu counting of aerobic bacteria; and (iv) metagenomic shotgun sequencing to predict expected tetracycline resistance based on known antimicrobial consumption in 10 Danish integrated slaughter pig herds. In addition, we evaluated whether fresh or manure floor samples constitute suitable proxies for intestinal sampling, using cfu counting, qPCR and metagenomic shotgun sequencing. Metagenomic read-mapping outperformed cultivation-based techniques in terms of predicting expected tetracycline resistance based on antimicrobial consumption. Our metagenomic approach had sufficient resolution to detect antimicrobial-induced changes to individual resistance gene abundances. Pen floor manure samples were found to represent rectal samples well when analysed using metagenomics, as they contain the same DNA with the exception of a few contaminating taxa that proliferate in the extraintestinal environment. We present a workflow, from sampling to interpretation, showing how resistance monitoring can be carried out in swine herds using a metagenomic approach. We propose metagenomic sequencing should be part of routine livestock resistance monitoring programmes and potentially of integrated One Health monitoring in all reservoirs.


Leadership Perceptions and Practices of Hospitality in Senior Care.
Senior care providers are increasingly focused on hospitality to distinguish themselves from competitors. A mixed-methods approach was used to examine perceptions of hospitality from leadership (i.e., administrators of nursing homes and assisted living facilities) and use of hospitality practices across settings and lines of service. Results indicated that hospitality practices readily exist in senior care settings (i.e., nursing homes, assisted living facilities), but may be referred to by names other than hospitality. There also appear to be more similarities than differences in practices across long-term care service lines (i.e., short- and long-stay nursing home residents, assisted living), suggesting that, regardless of provider type, hospitality in senior care is becoming part of the expected culture and cadre of services for residents. Overall, findings suggest hospitality practices are related to providers' census, payer mix, and organizational performance.


Crystal Structure of the Human Cannabinoid Receptor CB2.
The cannabinoid receptor CB2 is predominately expressed in the immune system, and selective modulation of CB2 without the psychoactivity of CB1 has therapeutic potential in inflammatory, fibrotic, and neurodegenerative diseases. Here, we report the crystal structure of human CB2 in complex with a rationally designed antagonist, AM10257, at 2.8 Å resolution. The CB2-AM10257 structure reveals a distinctly different binding pose compared with CB1. However, the extracellular portion of the antagonist-bound CB2 shares a high degree of conformational similarity with the agonist-bound CB1, which led to the discovery of AM10257's unexpected opposing functional profile of CB2 antagonism versus CB1 agonism. Further structural analysis using mutagenesis studies and molecular docking revealed the molecular basis of their function and selectivity for CB2 and CB1. Additional analyses of our designed antagonist and agonist pairs provide important insight into the activation mechanism of CB2. The present findings should facilitate rational drug design toward precise modulation of the endocannabinoid system.


Effect of transgenic plants expressing high levels of a tobacco anionic peroxidase on the toxicity of Anagrapha falcifera nucleopolyhedrovirus to Helicoverpa zea (Lepidoptera: Noctuidae).
Wild type and corresponding transgenic tomato (Lycopersicon esculentum Miller) and two tobacco (Nicotiana spp.) plants that express high levels of a tobacco anionic peroxidase were used to determine what type of interactions occurred between peroxidase altered plant chemistry and the baculovirus Anagrapha falcifera nucleopolyhedrovirus (AfMNPV) for control of neonate corn earworms, Helicoverpa zea (Boddie). Transgenic plants expressed approximately five to 400 times higher peroxidase activity than corresponding tissues of wild type plants. The H. zea larvae typically fed 1.5 times less on transgenic compared with wild type leaf disks. There was only one experiment (of three with tomato leaves) where the larvae that fed on transgenic leaves were less susceptible to the virus based on nonoverlapping 95% confidence intervals for LC50 values. When the exposure dose was corrected for reduced feeding on the transgenic leaf disks, the insecticidal activity of the virus was not significantly different for larvae fed on transgenic versus wild type plants. Eight other experiments (with tomato and two species of tobacco) indicated either no significant effect or enhanced susceptibility (when corrected for feeding rates) to the virus of larvae fed on the transgenic leaves. These results indicate enhanced insect resistance in plants expressing high levels of a specific anionic peroxidase may be compatible with applications of AfMNPV. Potential reasons for this compatibility are discussed.


Arthritis in rhesus monkeys experimentally infected with simian immunodeficiency virus (SIV/DELTA).
The joint tissues from 36 rhesus (age 2-5 years) infected with SIV/Delta were graded into four groups and then correlated with the following systemic immunologic parameters: numbers of CD4+, CD4+ plus CD29+, and CD20+ cells and SIV/Delta antigenemia. Grade I (n = 16) consisted of normal synovial membrane; grade II (n = 8) consisted of synovial hyperplasia; grade III (n = 8) consisted of a mononuclear cell infiltrate, and grade IV (n = 4) consisted of synovial membrane infiltration of syncytial cell and mononuclear type cells. Synovial membranes from 20 uninfected age-matched rhesus were compared with infected animals and were graded 1. Immunostaining of the tissue phase lymphocytes and viral antigen was performed using monoclonal antibodies commercially available and a monoclonal antibody produced against a core protein of the SIV/Delta agent. SIV/Delta infection resulted in a reduction in cells doubly stained for CD4+ and CD29+ and a relative increase in CD8+ stained cells. A significant (ANOVA) difference was not observed in CD4+, CD4+ plus CD29+, CD8+, or CD20+ among the various grades of arthritis. Viral antigen was demonstrated in syncytial cells of the grade IV reaction. This finding suggests that the SIV/Delta arthritis is a primary viral reaction.


[Six-minute-walking-test with and without oxygen in patients with COPD: comparison of walking distance and oxygen saturation in varying forms of application].
Patients afflicted with COPD and respiratory Failure often experience a decrease of oxygen saturation (SaO (2)) under physical strain. The aim of our study was to find out which changes occur in walking distance and SaO (2) under the application of Oxygen (O (2)) 2 l/min continous flow, under demand (D) and under normal air (RL) when performing the Six-Minute-Walking-Test (6MWT) and further, in which way do the 10 patients of the shortest walking distance group (group I) differ from the eo patients with the longest walking distance (group II) concerning the starter 6 MWT (under CF). 27 patients undertook a 6MWT three days in a row with CF, D and (RL), 6 minutes before (phase I), during (phase II) and after (phase III) the 6MWT oxygen was applied in CF (day I), D (day II) and RL (day III), the mean oxygen saturation in each phase was measured and the change (DeltaSaO (2)) during and after the 6MWT was calculated. Additionally we measured the DeltaSaO (2) between start and middle, as well as between middle and end of each phase. In close proximity to the tests FEV (1) and pO (2) was determined. In the total of all test persons there was no significant difference in the walking distance tetween the 3 forms of application. There was, however, a highly significant decrease of the oxygen saturation. The decrease in the two forms of oxygen application did not differ significantly. The decrease of SaO (2) under strain and the consecutive rise under rest occurred within the first 3 minutes of each phase. Patients of group II were often able to increase their walking distance under RL, whereas patients of group I decreased their walking distance further. In group II FEV (1) abs. was significantly higher, but FEV (1) % debit and pO (2) did not differ significantly between both groups. Patients with a long walking distance showed a marked learning effect even under RL, they presented a higher FEV (1), but not an increased pO (2). The phase of resaturation after the end of strain is short. Oxygen application through a demand valve with a flow rate of 2 l/min is not inferior to a continuous flow. In more than half of all patients the SaO (2) fell below 90 % under both forms of oxygen application, in conclusion the flow rate should be increased in these cases.


GLP-1 analog liraglutide enhances proinsulin processing in pancreatic β-cells via a PKA-dependent pathway.
Hyperproinsulinemia has gained increasing attention in the development of type 2 diabetes. Clinical studies have demonstrated that glucagon-like peptide-1 (GLP-1)-based therapies significantly decrease plasma proinsulin/insulin ratio in patients with type 2 diabetes. However, the underlying mechanism remains unclear. Prohormone convertase (PC)-1/3 and PC2 are primarily responsible for processing proinsulin to insulin in pancreatic β-cells. We have recently reported that Pax6 mutation down-regulated PC1/3 and PC2 expression, resulting in defective proinsulin processing in Pax6 heterozygous mutant (Pax6(m/+)) mice. In this study, we investigated whether and how liraglutide, a novel GLP-1 analog, modulated proinsulin processing. Our results showed that liraglutide significantly up-regulated PC1/3 expression and decreased the proinsulin to insulin ratio in both Pax6(m/+) and db/db diabetic mice. In the cultured mouse pancreatic β-cell line, Min6, liraglutide stimulated PC1/3 and PC2 expression and lowered the proinsulin to insulin ratio in a dose- and time-dependent manner. Moreover, the beneficial effects of liraglutide on PC1/3 and PC2 expression and proinsulin processing were dependent on the GLP-1 receptor-mediated cAMP/protein kinase A signaling pathway. The same mechanism was recapitulated in isolated mouse islets. In conclusion, liraglutide enhanced PC1/3- and PC2-dependent proinsulin processing in pancreatic β-cells through the activation of the GLP-1 receptor/cAMP/protein kinase A signaling pathway. Our study provides a new mechanism for improvement of pancreatic β-cell function by the GLP-1-based therapy.


Role of Pap Test terminology and age in the detection of carcinoma invasive and carcinoma in situ in medically underserved California women.
Our goals were to evaluate Pap Test findings classified by the Bethesda system, and follow up biopsies from participants in the California Breast and Cervical Cancer Control Program (Ca-BCCCP) for: 1) correlation in the detection of carcinoma in situ (CIS) and carcinoma invasive (CI), and 2) age-related trends, with discussion in the context of the 2001 ASCCP Management Guidelines. Women (n = 52,339) who had their initial screening Pap Tests with Ca-BCCCP between January 1995-December 1999 were followed for diagnostic services through December 2000. Descriptive and analytical methods were used in the analysis. Of the Pap results, 81.9% were negative, 10.6% showed infection, 4.7% showed an epithelial abnormality as defined by the Bethesda system (atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), or high-grade squamous intraepithelial lesion (HSIL)), 0.1% showed squamous-cell cancer (SCC), and 2.7% showed other or unsatisfactory. Subsequent to the initial Pap Test, follow-up results of carcinoma in situ (CIS) and carcinoma invasive (CI) accounted for 0.36% and 0.05% of the population, respectively. Among HSIL Pap Tests (n = 285), 40.7% had follow-up showing CIS. Among SCC Pap Tests, 17.9% had follow-up results of CIS and 28.6% CI. Of the 191 patients with CIS as a follow-up finding, the initial Pap smear showed: HSIL 60.7%, SCC 2.6%, LSIL 10.5%, ASCUS 13.6%, and negative or infection 9.9%. Of the 27 patients with CI, the initial Pap Test showed: HSIL 40.7%, SCC 29.6%, LSIL 7.4%, ASCUS 7.4%, and negative or infection 11.1%. Pap diagnoses of other or unsatisfactory accounted for 2.6% of the Pap results from patients with CIS and 3.7% of Pap results from patients with CI. Except for LSIL, there was an increasing age trend in the number of cases in each of Pap results, with the exception of age 65+ yr. However, the ratio of LSIL and ASCUS to negative cases decreased with age. (P < 0.0001 and 0.0293, respectively). HSIL Pap results indicate a reasonably high probability of CIS and CI. However, approximately 1/3 of patients with CIS and 1/4 of patients with CI presented with Pap diagnoses of less severity than HSIL. When a negative Pap Test result is chosen as reference group, there is a negative age trend for LSIL and ASCUS, and no age trend for other results. These findings all have important implications in the design of follow-up strategies, and support the 2001 ASCCP Consensus Guidelines for the Management of Women with Cervical Abnormalities.


Hastening death by selective disclosure of treatment options--beneficence or "euthanasia by deception"?
In this paper I make a radical claim regarding selective non-disclosure of treatment options that have some hope of prolonging a patient's life. I suggest that selective non-disclosure under such circumstances is tantamount to what might be called "euthanasia by deception." I offer a case to test the validity of my claim and to demonstrate how the failure to offer or, at least, to discuss renal dialysis in this case (and, by inference, any other form of treatment which has some hope of prolonging a patient's life) qualifies as paternalism in its most egregious form. I discuss the actions of the health care team and try to find some plausible reasons why they acted as they did. I conclude that there must be greater emphasis placed on teaching clinicians how better to incorporate frank, open and on-going discussion about the central elements of the therapeutic relationship with patients long before they lose decisional capacity.


[Indirect immunofluorescence and complement absorption test characterization of anti-brain antibodies in schizophrenia].
The content and tropism of anticerebral antibodies were examined in 20 schizophrenic patients using the indirect immunofluorescence and complement fixation tests. With the aid of the latter the antibodies were revealed in 15 patients, the antibodies to the homologous brain being more frequent in patients with a more severe, continuously progressing schizophrenia, while the antibodies to a heterologous (rat) brain were more often detected in patients with slowly progressing forms of the disease. In 18 patients, the indirect immunofluorescence test showed fixation of immunoglobulins on the nervous tissue components, such as, neurons, myelin, vascular walls. Rather frequently fluorescence of the microglia cells was observed: according to literary data this is not the case with sera of neurological patients. Of attention was a selective fluorescence of the canaliculi observed in examinations of the renal tissue. The data obtained point to a participation of the immunological reactions in the schizophrenia pathogenesis, these reactions involving various morphological and functional systems.


On the role of the cis Hoogsteen:sugar-edge family of base pairs in platforms and triplets-quantum chemical insights into RNA structural biology.
Base pairs belonging to the cis Hoogsteen:sugar-edge (H:S) family play important structural roles in folded RNA molecules. Several of these are present in internal loops, where they are involved in interactions leading to planar dinucleotide platforms which stabilize higher order structures such as base triplets and quartets. We report results of analysis of 30 representative examples spanning 16 possible base pair combinations, with several of them showing multimodality of base pairing geometry. The geometries of 23 of these base pairs were modeled directly from coordinates extracted from RNA crystal structures. The other seven were predicted structures which were modeled on the basis of observed isosteric analogues. After appropriate satisfaction of residual valencies, these structures were relaxed using the B3LYP/6-31G(d,p) method and interaction energies were derived at the RIMP2/aug-cc-pVDZ level of theory. The geometries for each of the studied base pairs have been characterized in terms of the number and nature of H-bonds, rmsd values observed on optimization, base pair geometrical parameters, and sugar pucker analysis. In addition to its evaluation, the nature of intermolecular interaction in these complexes was also analyzed using Morokuma decomposition. The gas phase interaction energies range between -5.2 and -20.6 kcal/mol and, in contrast to the H:S trans base pairs, show enhanced relative importance of the electron correlation component, indicative of the greater role of dispersion energy in stabilization of these base pairs. The rich variety of hydrogen bonding pattern, involving the flexible sugar edge, appears to hold the key to several features of structural motifs, such as planarity and propensity to participate in triplets, observed in this family of base pairs. This work explores these aspects by integrating database analysis, and detailed base pairing geometry analysis at the atomistic level, with ab initio computation of interaction energies. The study, involving alternative classification of base pairs and triplets, provides insights into intrinsic properties of these base pairs and their possible structural and functional roles.


Intravenous premedication with diazepam. A comparison between two vehicles.
Two preparations of diazepam, Valium Roche mixed Micelles and Diazemuls, were compared as intravenous premedicants in 119 patients undergoing minor gynaecological surgery. There were no differences between the formulations with regard to anxiolytic effects and systemic tolerance. There were no symptoms typical of thrombophlebitis in the Valium Roche Mixed-Micelles group and only one case in the Diazemuls group. Acute local tolerance was similar with both trial drugs and superior to conventional diazepam preparations. Based on the favourable results of the present study it can be concluded that such vehicles should be considered for any injectable preparation with a known tendency to produce venous irritation.


Comprehensive behavioral study of the effects of vanillin inhalation in mice.
Vanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects.


Effect of cognitive stimulation workshops on the self-esteem and cognition of the elderly A pilot project.
According to the WHO, by 2025 Brazil will be ranked sixth in the world in terms of proportion of elderly in the population. Within this scope, cognition plays a central role in the aging process, having an important association with quality of life, which suggests the need to develop intervention programs, such as cognitive training. To determine the effects of a program of cognitive stimulation workshops on the self-esteem and cognition of elderly people. Thirty-eight elderly subjects completed the three-step protocol: 1) Survey of demographic data and evaluation of cognition by a neuropsychological battery and of self-esteem using the Rosenberg Self-Esteem Scale (RSS), prior to training; 2) Participation in twelve cognitive stimulation workshops; and 3) Cognitive evaluation and RSS after the training. Results showed that the use of training produced positive effects on cognitive test performance of the elderly with and without cognitive impairment. By extension, this demonstrates positive impact on their self-esteem. These findings encourage investment in cognitive stimulation programs as a resource for improved cognition and quality of life for the elderly. Subjective cognitive complaint may have served as a predictor of decreased self-esteem; therefore, as training improved cognition, it also improved self-esteem.


Weights and hematology of wild black bears during hibernation.
We compared weights and hematological profiles of adult (greater than 3-yr-old) female black bears (Ursus americanus) during hibernation (after 8 January). We handled 28 bears one to four times (total of 47) over 4 yr of varying mast and berry production. Mean weight of lactating bears was greater (P less than 0.0001) than that of non-lactating females. White blood cells (P less than 0.05) and mean corpuscular volume (P = 0.005) also differed between lactating and non-lactating bears. Hemoglobin (P = 0.006) and mean corpuscular hemoglobin concentration (P = 0.02) varied among years; values were lowest during 1975, following decreased precipitation and the occurrence of a second year of mast and berry crop shortages in a three-year period. Significant (P less than 0.05) interaction between reproductive status (lactating versus non-lactating) and study year for hemoglobin, red blood cells, and packed cell volume, and increased mean corpuscular volume, suggested a greater nutritional challenge for lactating females compared to non-lactating females during the 1975 denning season. Our data suggest that hematological characteristics of denning bears may be more sensitive than weights as indicators of annual changes in nutritional status; however, other influential factors, in addition to mast and berry crop production, remain to be examined.


[Lactoferrin assay in urethritis and urethral prostatitis].
An immunochemical study of prostatic secretions in 97 patients with urethritis and urethroprostatitis has detected a significant rise of lactoferrin level in mixed infections (trichomonads + chlamydia and trichomonads + uroplasma--17 patients) versus control (14 healthy males) and group as a whole. In the control group a mean lactoferrin level was 51.2 +/- 8.4 mg/l (12 mg/l-67.3 mg/l), in the group as a whole 106 +/- 41.5 mg/l (19.5 mg/l to 334.8 mg/l) in patients with mixed infection 221.25 (102.9 mg/l to 334.8 mg/l). The assessment of diagnostic significance of the immunochemical test for lactoferrin in detection of mixed infections in urethritis and urethroprostatitis has shown that in threshold level of 150 mg/l the test's specificity was 87.5%, sensitivity 94.1%, effectiveness 88.65%, prognostic value of positive result 61.5%, of negative result 98.59%; in threshold level 200 mg/l the respective values were 100, 52.9, 91.75, 100 and 90.9%. Practical application of the proposed immunochemical test in detection of mono- and mixed infection is discussed.


Rehabilitative rheumatology content in current rehabilitation medicine training programs.
The Council on Rehabilitative Rheumatology of the American Rheumatism Association, through the Education Subcommittee, surveyed directors of 69 approved rehabilitation medicine residency training programs to assess the nature of training in rehabilitative-rheumatology and whether the directors believed this training to be adequate. Sixty-one directors responded, with 84% of the respondents reporting a rheumatology department in their hospitals and 43% reporting a formal rotation for their residents in rheumatology. Fifty-nine (97%) reported their residents received lectures in rheumatology. Fifty-five (90%) reported lectures given by a physiatrist in the rehabilitative management of rheumatic diseases. Only 21 (34%) reported a physiatrist-attended rheumatology outpatient clinic. Fifty-one (82%) desired a closer liaison with the rheumatology department. Thirty-seven (61%) indicated their residents received adequate training on the diagnosis of rheumatic diseases, and 46 (75%) adequate training in rehabilitative management, while 59 (97%) desired a concise handbook which emphasizes the rehabilitative management of rheumatic diseases. A previous survey of 100 arthritis fellowship programs approved by the American Medical Association brought 81 responses, of which only 43% considered that their Fellows had adequate training in rehabilitative rheumatology. Physiatrists attended clinics 21% of the time and patient care rounds 19%. Ninety-four percent desired a syllabus. Both surveys indicated limited interaction between the two specialties and leads us to conclude that a rehabilitative-rheumatology handbook would be desirable, closer liaison of rehabilitation faculty with rheumatology faculty is needed to respond to individual training needs, more active participation by a physiatrist in patient care conferences may be necessary for adequate education in rehabilitative-rheumatology.


A new general glucose homeostatic model using a proportional-integral-derivative controller.
The glucose-insulin system is a challenging process to model due to the feedback mechanisms present, hence the implementation of a model-based approach to the system is an on-going and challenging research area. A new approach is proposed here which provides an effective way of characterising glycaemic regulation. The resulting model is built on the premise that there are three phases of insulin secretion, similar to those seen in a proportional-integral-derivative (PID) type controller used in engineering control problems. The model relates these three phases to a biological understanding of the system, as well as the logical premise that the homeostatic mechanisms will maintain very tight control of the system. It includes states for insulin, glucose, insulin action and a state to simulate an integral function of glucose. Structural identifiability analysis was performed on the model to determine whether a unique set of parameter values could be identified from the available observations, which should permit meaningful conclusions to be drawn from parameter estimation. Although two parameters--glucose production rate and the proportional control coefficient--were found to be unidentifiable, the former is not a concern as this is known to be impossible to measure without a tracer experiment, and the latter can be easily estimated from other means. Subsequent parameter estimation using Intravenous Glucose Tolerance Test (IVGTT) and hyperglycaemic clamp data was performed and subsequent model simulations have shown good agreement with respect to these real data.


Endothelial glycocalyx breakdown is mediated by angiopoietin-2.
The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal surface of the endothelium, provides a first vasoprotective barrier against vascular leakage and adhesion in sepsis and vessel inflammation. Angiopoietin-2 (Angpt-2), an antagonist of the endothelium-stabilizing receptor Tie2 secreted by endothelial cells, promotes vascular permeability through cellular contraction and junctional disintegration. We hypothesized that Angpt-2 might also mediate the breakdown of the eGC. Using confocal and atomic force microscopy, we show that exogenous Angpt-2 induces a rapid loss of the eGC in endothelial cells in vitro. Glycocalyx deterioration involves the specific loss of its main constituent heparan sulphate, paralleled by the secretion of the heparan sulphate-specific heparanase from late endosomal/lysosomal stores. Corresponding in vivo experiments revealed that exogenous Angpt-2 leads to heparanase-dependent eGC breakdown, which contributes to plasma leakage and leukocyte recruitment in vivo. Our data indicate that eGC breakdown is mediated by Angpt-2 in a non-redundant manner.


Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice.
Antigens and infectious agents that stimulate interferon alpha(IFN-alpha) production in mice induce antibody responses that are predominantly of the immunoglobulin (Ig)G2a isotype and contain little or no IgE. This suggested the possibility that IFN-alpha might have a role in directing Ig isotype selection. Consistent with this possibility, we have found that injection of mice with recombinant mouse IFN-alpha suppresses IgE secretion, enhances IgG2a secretion, and has no independent effect on IgG1 secretion in mice stimulated with a foreign anti-IgD antibody. Injection of mice with polyinosinic acid.polycytidylic acid (poly I.C), an inducer of macrophage IFN-alpha production, also suppresses the anti-IgD antibody-induced IgE response and stimulates the IgG2a response; these effects are blocked by a sheep antibody that neutralizes mouse IFN-alpha/beta. Both recombinant IFN-alpha and poly I.C have maximum IgE suppressive and IgG2a stimulatory effects when injected early in the anti-IgD antibody-induced immune response. Addition of IFN-alpha to mouse B cells cultured with lipopolysaccharide (LPS) + interleukin 4 (IL-4) suppresses both IgG1 and IgE production, but much less potently than IFN-gamma. IFN-alpha suppresses anti-IgD antibody-induced increases in the level of splenic IL-4 mRNA, but enhances the anti-IgD antibody-induced increase in the splenic level of IFN-gamma mRNA. These results are consistent with the effect of IFN-alpha on Ig isotype expression in mice, as IL-4 stimulates IgE and suppresses IgG2a secretion while IFN-gamma exerts opposite effects. These observations suggest that antigen presenting cells, by secreting IFN-alpha early in the course of an immune response, can influence the nature of that response both through direct effects on B cells and by influencing the differentiation of T cells.


Highly Efficient Generation of Pigs Harboring a Partial Deletion of the CD163 SRCR5 Domain, Which Are Fully Resistant to Porcine Reproductive and Respiratory Syndrome Virus 2 Infection.
Porcine reproductive and respiratory syndrome virus (PRRSV) 1 and 2 differ in their recognition of CD163. Substitution of porcine CD163 SRCR5 domain with a human CD163-like SRCR8 confers resistance to PRRSV 1 but not PRRSV 2. The deletion of CD163 SRCR5 has been shown to confer resistance to PRRSV 1 in vivo and both PRRSV 1 and 2 in vitro. However, the anti-PRRSV 2 activity of modifying the CD163 SRCR5 domain has not yet been reported. Here, we describe the highly efficient generation of two pig breeds (Liang Guang Small Spotted and Large White pigs) lacking a short region of CD163 SRCR5, including the ligand-binding pocket. We generated a large number of gene-edited Large White pigs of the F0 generation for use in viral challenge studies. The results of this study show that these pigs are completely resistant to infection by species 2 PRRSV, JXA1, and MY strains. There were no clinical symptoms, pathological abnormalities, viremia, or anti-PRRSV antibodies in the CD163 SRCR5-edited pigs compared to wild-type controls after viral challenge. Porcine alveolar macrophages (PAMs) isolated from CD163 SRCR5-edited Large White pigs also displayed resistance to PRRSV in vitro. In addition, CD163 SRCR5-edited PAMs still exhibited a cytokine response to PRRSV infection, and no significant difference was observed in cytokine expression compared to wild-type PAMs. Taken together, these data suggest that CD163 SRCR5-edited pigs are resistant to PRRSV 2, providing a basis for the establishment of PRRSV-resistant pig lines for commercial application and further investigation of the essential region of SRCR5 involved in virus infection.


Study of stress-induced temporomandibular disorders among dental students: An institutional study.
The aim and objectives of this study are to investigate the various types of stress-inducing factors, most prevalent etiological factor and to determine the correlation between stress and temporomandibular disorders (TMDs) in Dental students in Modinagar, Ghaziabad, Uttar Pradesh. A sample of 450 students were selected for the study divided into two groups of undergraduate (UG) and postgraduate (PG) students further subdivided into UG (1st, 2nd, 3rd, and 4th, interns) and PG (1st, 2nd, 3rd year). Study includes clinical evaluation of temporomandibular joint (TMJ) system (TMJ sounds, muscles of mastications, mouth opening, and range of mandibular motion) and questionnaire which covers demographic data (i.e., age, sex, and academic year), TMD symptoms and TMD signs along with standardized scales related to stress dental environmental stress scale and perceived stress scale (PSS). Most of the students included into study are mostly of 21-25 years of age (64.3%), males (52.7%), females 47.3% with more number of UGs (91.4%) predominantly 1st year students (23.9%). Headache was found to be the most prevalent TMD symptom (26.2%) followed by clicking (24.9%), pain on clicking (5.5%), jaw lock (3.4), and difficulty in mouth opening (0.9%). Clicking was found to be the most prevalent TMD sign (24.9%) among dental students followed by deviation (16.3%), muscle tenderness (14.3%), and TMJ pain (5.7%). The most prevalent TMD was disc displacement 22.6% followed by myofascial pain dysfunction syndrome (MPDS) with disc displacement (13.5%) and MPDS (3.8%). TMD was higher in UG females students of 21--25 years of age group, dental environment stress scale score and PSS score shows statistically significant results. Stress is a significant etiologic factor involved in initiation and maintenance of TMDs in Dental students.


Placement of health promotion columns in suburban newspapers--an analysis.
In the fall of 1982, the Office of Disease Prevention and Health Promotion, Public Health Service, engaged the services of the North American Precis Syndicate, Inc., to distribute two columns on health promotion to suburban newspapers. An analysis of the placement of these two health promotion columns in local newspapers was undertaken to determine if this method of disseminating health information to the public is effective and cost-conscious. The information gained from this analysis, though limited in scope, provides information to decision makers responsible for disseminating health information to the public. North American Precis Syndicate, Inc. (NAPS), distributes public information through various channels. One service NAPS provides is a clip sheet of publication-ready newspaper columns complete with artwork which an editor can "clip" and use directly in a newspaper. NAPS is able to use existing information and artwork to develop its columns, so agency staff time is minimal in developing material. NAPS also provides clippings of the articles as they actually appear in the 3,800 suburban newspapers it services. It is the information from the NAPS "clipping service" on which this report is based.


Beckwith-Wiedemann syndrome with multiple hepatic and cutaneous hemangiomas in a female patient of Albanian origin: Diagnostic and therapeutic considerations.
We describe a 2-month-old female infant with macroglossia, macrosomia, omphalocele, neonatal hypoglycemia, earlobe creases, low nasal bridge, midface retrusion, syndromic facies and multiple cutaneous and hepatic hemangiomas (HH). Genetic evaluation confirmed the diagnosis of Beckwith-Wiedemann Syndrome (BWS) with mosaic uniparental disomy 11 as the underlying genetic mechanism suggested by partial hypermethylation of H19/IGF2:IG-DMR and partial hypomethylation of KCNQ1OT1:TSS-DMR on chromosome 11p15.5. Pediatric endocrinology and cardiology assessments were normal. No malignant liver or renal tumors were detected during the follow-up period. Treatment with propranolol was started for the multiple HH, according to international recommendations. At 3-, 6-, and 9-month follow up, a gradual decrease in the size of the hemangiomas and AFP levels was observed, without side effects. This is the fifth case in the literature combining HH and BWS, and among these, the third case with this specific genetic defect suggesting a possible association between HH and BWS caused by 11 paternal uniparental disomy [upd(11)pat]. The case also highlights that if treatment is warranted, then oral propranolol can be used for the management of infantile HH in BWS patients similarly to non-BWS patients.


Human hippocampal theta oscillations and the formation of episodic memories.
The importance of the hippocampal theta oscillation (4-8 Hz) to memory formation has been well-established through studies in animals, prompting researchers to propose comprehensive theories of memory and learning that rely on theta oscillations for integrating information in the hippocampus and neocortex. Yet, empirical evidence for the importance of 4-8 Hz hippocampal theta oscillations to memory formation in humans is equivocal at best. To clarify this apparent interspecies discrepancy, we recorded intracranial EEG (iEEG) data from 237 hippocampal electrodes in 33 neurosurgical patients as they performed an episodic memory task. We identified two distinct patterns of hippocampal oscillations, at ∼3 and ∼8 Hz, which are at the edges of the traditional 4-8 Hz human theta band. The 3 Hz "slow-theta" oscillation exhibited higher power during successful memory encoding and was functionally linked to gamma oscillations, but similar patterns were not present for the 8 Hz "fast-theta" oscillation. For episodic memory, slow-theta oscillations in the human hippocampus appear to be analogous to the memory-related theta oscillations observed in animals. Both fast-theta and slow-theta oscillations exhibit evidence of phase synchrony with oscillations in the temporal cortex. We discuss our findings in the context of recent research on the electrophysiology of human memory and spatial navigation, and explore the implications of this result for theories of cortico-hippocampal communication.


Chromosome 1p loss evaluation in anaplastic oligodendrogliomas.
The chromosome (chr) 1p deletion is a favorable biomarker in oligodendroglial tumors and is even more powerful a marker when combined with chr 19q loss. As a result, the 1p deletion is taken into account more and more in clinical trials and the management of patients. However, the laboratory technique implemented for detection of this biomarker has been a topic of debate. To illustrate the usefulness of evaluating multiple loci, we here report two anaplastic oligodendrogliomas that were investigated using fluorescent in situ hybridization (FISH) and bacterial artificial chromosome (BAC)-array-based comparative genomic hybridization (aCGH). Indeed, segmental analysis using FISH, limited to chr 1p36 was unable to discriminate between complete and partial deletions of chrs 1p. However, complete and partial deletions of 1p are reported to have distinct clinical outcomes. Our results illustrate that aCGH (or other multiple loci technologies) provide complementary information to single locus technologies such as FISH because multiple loci technologies can evaluate the extent of the chr 1p deletion.


Discovery of the First Environment-Sensitive Fluorescent Probe for GPR120 (FFA4) Imaging.
GPR120, which is activated by long-chain free fatty acids (FFAs), has been recognized as a new attractive target for the treatment of type 2 diabetes and metabolic disease. The visualization and location of GPR120 in native cells can provide powerful information for guiding the physiological and pathological studies of GPR120. We report herein the first potent fluorescent probes that sensitively detect GPR120. We designed and synthesized a series of novel environment-sensitive probes with suitable fluorescence property, high biological activity on the GPR120, and acceptable cytotoxicity. These fluorescent probes targeting GPR120 are expected to expand the toolkit for further studies on GPR120.


Pest categorisation of Maconellicoccus hirsutus.
The EFSA Panel on Plant Health performed a pest categorisation of Maconellicoccus hirsutus (Hemiptera: Pseudococcidae), the pink hibiscus mealybug, for the EU. M. hirsutus is native to Southern Asia and has established in many countries in tropical and subtropical regions throughout the world. Within the EU, the pest has been reported from Cyprus and Greece (Rhodes). M. hirsutus is not listed in Annex II of Commission Implementing Regulation (EU) 2019/2072. It is highly polyphagous, feeding on plants assigned to 229 genera in 78 plant families, and shows some preference for hosts in the families Malvaceae, Fabaceae and Moraceae. Economically important crops in the EU such as cotton (Gossypium spp.), citrus (Citrus spp.), ornamentals (Hibiscus spp.), grapes (Vitis vinifera), soybean (Glycinae max), avocado (Persea americana) and mulberry trees (Morus alba) may be significantly affected by M. hirsutus. The lower and upper developmental temperature threshold of M. hirsutus on Hibiscus rosa-sinensis are 14.5 and 35.0°C, respectively, with optimal female development estimated to be at 29.0°C. There are about 10 generations a year in the subtropics but as many as 15 may occur under optimal conditions. Plants for planting, fruits, vegetables and cut flowers provide potential pathways for entry into the EU. Climatic conditions in EU member states around the Mediterranean Sea and host plant availability in those areas are conducive for establishment. The introduction of M. hirsutus is expected to have an economic impact in the EU through damage to various ornamental plants, as already observed in Cyprus and Greece, and reduction in yield and quality of many significant crops. Phytosanitary measures are available to reduce the likelihood of entry and further spread. Some uncertainties include the area of establishment, whether it could become a greenhouse pest, impact, and the influence of natural enemies. M. hirsutus meets the criteria that are within the remit of EFSA to assess for it to be regarded as a potential Union quarantine pest.


Self-Supervised Segmentation of 3D Fluorescence Microscopy Images Using CycleGAN.
In recent years, deep learning models have been extensively applied for the segmentation of microscopy images to efficiently and accurately quantify and characterize cells, nuclei, and other biological structures. However, typically these are supervised models that require large amounts of training data that are manually annotated to create the ground-truth. Since manual annotation of these segmentation masks is difficult and time-consuming, specially in 3D, we sought to develop a self-supervised segmentation method.Our method is based on an image-to-image translation model, the CycleGAN, which we use to learn the mapping from the fluorescence microscopy images domain to the segmentation domain. We exploit the fact that CycleGAN does not require paired data and train the model using synthetic masks, instead of manually labeled masks. These masks are created automatically based on the approximate shapes and sizes of the nuclei and Golgi, thus manual image segmentation is not needed in our proposed approach.The experimental results obtained with the proposed CycleGAN model are compared with two well-known supervised segmentation models: 3D U-Net [1] and Vox2Vox [2]. The CycleGAN model led to the following results: Dice coefficient of 78.07% for the nuclei class and 67.73% for the Golgi class with a difference of only 1.4% and 0.61% compared to the best results obtained with the supervised models Vox2Vox and 3D U-Net, respectively. Moreover, training and testing the CycleGAN model is about 5.78 times faster in comparison with the 3D U-Net model. Our results show that without manual annotation effort we can train a model that performs similarly to supervised models for the segmentation of organelles in 3D microscopy images.Clinical relevance- Segmentation of cell organelles in microscopy images is an important step to extract several features, such as the morphology, density, size, shape and texture of these organelles. These quantitative analyses provide valuable information to classify and diagnose diseases, and to study biological processes.


Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.
To describe the genetic characteristics of the cohort enrolled in the international multicentre progression of Stargardt disease 1 (STGD1) studies (ProgStar) and to determine geographic differences based on the allele frequency. 345 participants with a clinical diagnosis of STGD1 and harbouring at least one disease-causing ABCA4 variant were enrolled from 9 centres in the USA and Europe. All variants were reviewed and in silico analysis was performed including allele frequency in public databases and pathogenicity predictions. Participants with multiple likely pathogenic variants were classified into four national subgroups (USA, UK, France, Germany), with subsequent comparison analysis of the allele frequency for each prevalent allele. 211 likely pathogenic variants were identified in the total cohort, including missense (63%), splice site alteration (18%), stop (9%) and others. 50 variants were novel. Exclusively missense variants were detected in 139 (50%) of 279 patients with multiple pathogenic variants. The three most prevalent variants of these patients with multiple pathogenic variants were p.G1961E (15%), p.G863A (7%) and c.5461-10 T>C (5%). Subgroup analysis revealed a statistically significant difference between the four recruiting nations in the allele frequency of nine variants. There is a large spectrum of ABCA4 sequence variants, including 50 novel variants, in a well-characterised cohort thereby further adding to the unique allelic heterogeneity in STGD1. Approximately half of the cohort harbours missense variants only, indicating a relatively mild phenotype of the ProgStar cohort. There are significant differences in allele frequencies between nations, although the three most prevalent variants are shared as frequent variants.


E-scooters: Still the new kid on the transport block. Assessing e-scooter legislation knowledge and illegal riding behaviour.
The use of e-scooters is rapidly increasing in cities, leading to their integration into the transportation system. However, numerous collisions involving e-scooters, including some resulting in fatalities, have been reported since their introduction. These incidents indicate that the potential dangers posed by e-scooters may be underestimated. Research suggests that a significant factor contributing to these collisions is the prevalence of illegal riding behaviour exhibited by many riders. This paper presents three studies that aimed to assess the understanding of e-scooter riders and non-riders of the current legislation across various riding scenarios and link it to their profile, riding habits, and their proneness to engage in illegal riding behaviours. Study 1 utilised questionnaires to survey participants and gather information about their profiles and self-reported illegal riding behaviour. Study 2 focused on assessing participants' knowledge of the current e-scooter legislation through different everyday riding scenarios. Study 3 featured short video clips from the rider's perspective to determine the proneness of participants to engage in illegal riding behaviour and explore the potential relationship between these behaviours and their understanding of e-scooter rules. The findings revealed that e-scooter riders were generally younger and exhibited a higher propensity for engaging in illegal riding behaviour than non-users. Both groups demonstrated limited knowledge regarding various aspects of the current e-scooter legislation, particularly related to parking, speeding, and designated infrastructure. While e-scooter riders demonstrated relatively greater knowledge of the e-scooter rules, this was not consistently observed across all areas, particularly in relation to riding on pavements (pedestrian footpaths). Furthermore, Study 3 revealed that participants with better knowledge of the current legislation were less likely to engage in illegal riding behaviour. These findings suggest a need for targeted interventions and educational campaigns to improve riders' understanding of regulations and promote safer riding practices. Implementing training programs for e-scooter safety could significantly enhance riders' awareness of the associated dangers, fostering responsible e-scooter use.


Rice Flour: A Promising Food Material for Nutrition and Global Health.
Hunger and malnutrition, especially children, are still global issues today. Rice is a staple food for more than half of the world population and important nutritional source of not only carbohydrate but also protein. In recent aging societies, protein-energy malnutrition in elderly people emerges also as a social issue. Malnutrition in elderly people raises the risk of falling into age-related chronic diseases. Nutritional care can prevent elderly people from such age-related diseases. Rice and rice flour would be good foodstuff for preparation of diet suitable for and preferred by elderly people. Protein content of rice grains, like the other cereal grains, is less than 10% by weight, which is a little lower than meat and cheese, but higher than dairy milk and yoghurt. Nutritional quality of rice proteins is higher than the other cereal grains. Such relatively higher nutritional quality of rice proteins could be due to high copies of glutelin genes evolved from an ancestral gene common to soybean glycinin and resultant high content of legume-type seed storage proteins. Recently, rice flour became to be utilized for various processed food. The rice seed proteins as well as starch are accumulated in specific organelles termed protein bodies and amyloplast in the cells of endosperm and aleurone layer. By milling rice grains to flour particles consisting of protein and starch nanoparticles, processing characteristics of rice starch and proteins could be changed. To develop rice-based processed food for prevention of malnutrition, rice flour particles from various different rice sources could be blended for desired nutritional composition without spoiling the value of product food.


Study of the antinociceptive action of the ethanolic extract and the triterpene 24-hydroxytormentic acid isolated from the stem bark of Ocotea suaveolens.
We describe here the antinociceptive action of the crude extract (CE), the chemical isolation and characterisation and preliminary pharmacological analysis of 24-hydroxytormentic acid, isolated from the stem bark of Ocotea suaveolens (Lauraceae). The CE given by i.p. or p.o. routes, 30 min and 1 h prior, produced significant inhibition of abdominal constrictions caused by acetic acid and also inhibited both phases of formalin-induced licking in mice. The antinociception caused by the CE, given by i.p. and p.o. routes, lasted up to 4 and 2h, respectively. When assessed in the hot-plate test, the CE was inactive. Its antinociceptive action was not associated with non-specific effects such as muscle relaxation or sedation. The antinociception of CE was not influenced by naloxone, L-arginine or DL-p-chlorophenylalanine methyl ester, when assessed against the formalin assay. The triterpene 24-hydroxytormentic acid, given i.p. 30 min before testing, produced significant, dose-related and equipotent antinociceptive action against both phases of formalin-induced licking in mice. These results demonstrate, for the first time, the occurrence of the triterpene 24-hydroxytormentic acid in the stem bark of Ocotea suaveolens, and show that the CE and 24-hydroxytormentic acid exhibit marked antinociception against the neurogenic and the inflamamtory algesic responses induced by formalin in mice. The mechanism by which this compound and CE produces antinociception still remains unclear, but is unlikely to involve the activation of opioid, nitric oxide or serotonin systems or non-specific peripheral or central depressant actions.


Type 2 diabetes mouse model TallyHo carries an obesity gene on chromosome 6 that exaggerates dietary obesity.
The TallyHo (TH) mouse strain is a polygenic model for Type 2 diabetes with obesity. Genetic analysis in backcross progeny from a cross between F1 [C57BL/6J (B6) x TH] and TH mice mapped a quantitative trait locus (QTL) named TH-associated body weight 2 (tabw2) to chromosome 6. The TH-derived allele is associated with increased body weight. As a first step to identify the molecular basis of this obesity QTL, we constructed a congenic line of mice on the B6 genetic background that carries a genomic region from TH mice containing tabw2. Congenic mice homozygous for tabw2 (B6.TH-tabw2/tabw2) fed a chow diet exhibited slightly, but significantly, higher body weight and body fat and plasma leptin levels compared with controls (B6.TH-+/+). This difference was exacerbated when the animals were maintained on a high-fat and high-sucrose (HFS) diet. The diet-induced obesity in tabw2 congenic mice is accompanied by hyperleptinemia, mild hyperinsulinemia, impaired glucose tolerance, and reduced glucose uptake in adipose tissue in response to insulin administration. Using F2 progeny fed a HFS diet from an intercross of B6.TH-tabw2/+ mice, we were able to refine the map position of the tabw2 obesity susceptibility locus to a 15-cM region (95% confidence interval) extending distally from the marker D6Mit102. In summary, tabw2 congenic mice are a new animal model for diet-induced obesity that will be valuable for the study of gene-diet interactions.


Fast full-color computational imaging with single-pixel detectors.
Single-pixel detectors can be used as imaging devices by making use of structured illumination. These systems work by correlating a changing incident light field with signals measured on a photodiode to derive an image of an object. In this work we demonstrate a system that utilizes a digital light projector to illuminate a scene with approximately 1300 different light patterns every second and correlate these with the back scattered light measured by three spectrally-filtered single-pixel photodetectors to produce a full-color high-quality image in a few seconds of data acquisition. We utilize a differential light projection method to self normalize the measured signals, improving the reconstruction quality whilst making the system robust to external sources of noise. This technique can readily be extended for imaging applications at non-visible wavebands.


Optimizing Mycophenolic Acid Exposure in Kidney Transplant Recipients: Time for Target Concentration Intervention.
The immunosuppressive agent mycophenolate is used extensively in kidney transplantation, yet dosing strategy applied varies markedly from fixed dosing ("one-dose-fits-all"), to mycophenolic acid (MPA) trough concentration monitoring, to dose optimization to an MPA exposure target (as area under the concentration-time curve [MPA AUC0-12]). This relates in part to inconsistent results in prospective trials of concentration-controlled dosing (CCD). In this review, the totality of evidence supporting mycophenolate CCD is examined: pharmacological characteristics, observational data linking exposure to efficacy and toxicities, and randomized controlled trials of CCD, with attention to dose optimization method and exposure achieved. Fixed dosing of mycophenolate consistently leads to underexposure associated with rejection, as well as overexposure associated with toxicities. When CCD is driven by pharmacokinetic calculation to a target concentration (target concentration intervention), MPA exposure is successfully controlled and clinical benefits are seen. There remains a need for consensus on practical aspects of mycophenolate target concentration intervention in contemporary tacrolimus-containing regimens and future research to define maintenance phase exposure targets. However, given ongoing consequences of both overimmunosuppression and underimmunosuppression in kidney transplantation, impacting short- and long-term outcomes, these should be a priority. The imprecise "one-dose-fits-all" approach should be replaced by the clinically proven MPA target concentration strategy.


Glucocorticoid regulation of a transcription factor that binds an initiator-like element in the murine thymidine kinase (Tk-1) promoter.
Glucocorticoids inhibit transcription of the murine cytoplasmic thymidine kinase gene (Tk-1). Glucocorticoid regulation of Tk-1 transcription can be demonstrated in cells that are arrested in late G1. This observation indicates that inhibition of Tk-1 expression is not dependent upon redistribution within the cell cycle but is due to glucocorticoid regulation of this gene. Transfection studies have been carried out using chimeric genes in which restriction fragments of the Tk-1 promoter were fused to chloramphenicol acetyltransferase or neomycin phosphotransferase. These chimeric reporters were assayed for stable expression and glucocorticoid regulation in P1798 lymphoma cells. A 140-bp fragment, extending from -143 to -3 bp with respect to the thymidine kinase translational start site, was capable of both basal and glucocorticoid-regulated transcription of reporter genes. The extent of inhibition by glucocorticoids was similar to that observed for the endogenous gene, and no increase in basal expression or the extent of inhibition was observed with constructs containing additional 5'-flanking DNA. The 140-bp Tk-1 core promoter fragment binds to transcription factors in extracts from P1798 cells. Control cell extracts contain factors that bind to and protect (from deoxyribonuclease I) a distal promoter element from -106 to -87 bp, relative to the translational start site. A second, proximal element was protected at -43 to -36 bp. The proximal element of the Tk-1 promoter resembles an RNA polymerase II initiator element. No other elements were protected. Glucocorticoids inhibit the amount or activity of the transcription factor that binds to this initiator-like element within the Tk-1 promoter. This element, when fused to upstream activation sequences from the herpes simplex virus thymidine kinase promoter, conveys glucocorticoid sensitivity in cis.


Mental health policy development: case study of Cambodia.
To identify key issues in the mental health policy development process in Cambodia that will contribute to an increased understanding of how mental health policy gets on the public policy agenda, how it stays there and why policy implementation fails or succeeds. The research was formative because mental health policy analysis is a young and newly emerging discipline. A retrospective case study methodology was used to research the development of the draft Cambodian Mental Health Plan 2003-2022. Ten key informants involved in the policy development process were interviewed using a semistructured questionnaire designed to collect qualitative data about the policy formation process, stakeholders and context. The research identified key issues influencing mental health policy development. These are the need to include the Ministry of Health (MoH) in the development of mental health plans; the significance of timing; the usefulness of mental health plans; the impact of the post-conflict context on policy development; and the evolution of stakeholder groups and their need to learn how to debate the merits of mental health reform. The findings are formative given methodology limitations. However, important insight is provided into the dynamics of the policy development processes that occurred in Cambodia. This allows the generation of important hypotheses for future mental health policy process research in both Cambodia and other post-conflict developing countries.


Measuring kinematic changes of the foot using a gyro sensor during intense running.
Gyro sensor has been used to measure foot pronation during running with reliable results in previous studies, and the signals were not affected by the vibration of heel strikes. The purpose of this study was to observe the kinematic changes of the foot during intense running using a 3-axis gyro sensor. Fifteen male participants (average age: 24.5 ± 1.7 years; mean height: 174.1 ± 3.3 cm; mean body weight: 71.0 ± 5.5 kg) were recruited in this study. Foot kinematic changes were observed in 30-min intense running protocols. The comparisons of the signals from gyro and motion analysis system were also performed to determine the accuracy of the gyro and showed positive results. In the main experiment, the ankle range of motion (ROM) in the frontal plane, measured using a motion system, showed a significant increase over time. Accordingly, peak angular velocity in the frontal plane also showed a significant increase. The correlation between ankle ROM and peak angular velocity in the frontal plane is significantly high (r = 0.975). Moreover, peak angular velocity in the frontal plane is also significantly correlated with both rate of perceived exertion (RPE) (r = 0.911) and heart rate (r = 0.960). This study concluded that an alarm system for foot kinematic changes related to running injuries can be built based on the peak angular velocity of the foot in the frontal plane.


The prevalence and risk factors of low back pain in the eastern Black Sea region of Turkey.
Low back pain (LBP) is a public health problem commonly seen in all societies. The aim of this study was to determine the prevalence and specific risk factors of low back pain (LBP) in the central and outlying districts of the province of Trabzon, a Black Sea region of Turkey. A random sample of 7897 (4006 men and 3789 women) adults was collected by using sampling techniques of stratification. In this study questionnaires were completed at face-to-face interviews with participants selected on the basis of place of residence, gender and age group. The used variables in this study were: use of cigarettes, status of marriage, level of education, and presence of chronic disease, the prevalence of lifetime LBP and of LBP in the preceding year. Chronic LBP was determined as being present for more than 6 weeks. The lifetime prevalence of LBP in the general population was determined at 62.1%. Prevalence in the preceding year was 46.1%, and that of LBP lasting more than six week was 18.1%. Lifetime prevalence of LBP, prevalence of LBP in the preceding year and prevalence of pain lasting more than six week were all statistically significantly higher in women (p< 0.001). Use of cigarettes, female gender, marriage, a low level of education and presence of chronic disease were identified as independent risk factors for LBP (p< 0.001). Lower back pain is a common public health problem. Recommendations were made for local health services to prevent LBP, including health education through combating chronic diseases, reducing cigarette consumption, improvement of working environments and life styles.


Effect of oral contraceptives on tryptophan and tyrosine availability: evidence for a possible contribution to mental depression.
The plasma concentrations of branched-chain and aromatic amino acids, free tryptophan, and kynurenine have been determined in oral contraceptive users and comparable controls. There were no differences between progestogen users and controls in either of the biochemical measurements. The estrogen-progestogen users showed elevated plasma levels of total tryptophan and decreased levels of tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. Mestranol was less potent than ethinylestradiol on the effect on plasma tyrosine. There was a clear trend that the incidence of adverse reactions was related to the decrease in tyrosine levels. The plasma ratio of tryptophan to competing amino acids was increased in the estrogen-progestogen users, whereas the ratio of tyrosine to competitors was severely decreased suggesting a decreased brain tyrosine concentration. It is suggested that a substrate-limited reduction in brain noradrenaline synthesis may contribute to the occurrence of depressive symptoms in susceptible individuals on estrogen-progestogen contraceptives.


DNA sequence homology between two co-linear loci on the HSV genome which have different transforming abilities.
A transcription unit at the herpes simplex virus (HSV) type 2 transforming region, mtr-2 (map coordinates 0.580-0.625), comprises two early, unspliced mRNAs of 4.5 kb and 1.2 kb which are 3' co-terminal; a region including that specifying the 1.2-kb mRNA has been sequenced. The putative translated portions of these two mRNAs do not overlap and this feature, together with the arrangement of the mRNAs, is similar to the apparently equivalent co-linear HSV-1 locus which however does not transform. A putative stem and loops structure containing a TATA box is located upstream from the 5' terminus of the 1.2-kb mRNA within the translated portion of the 4.5-kb mRNA. Evidence for the generation of this structure by intra-strand reassociation under our hybridisation conditions has been obtained and possibilities are that it may function as a transcription-activated promoter or as an RNA polymerase pause site. A comparison of the equivalent HSV-2 and HSV-1 regions reveals a conserved sequence downstream from the 3' co-terminus which is present at a similar location in many eukaryotic genes (consensus sequence YGTGTTYY). The overall sequence conservation at this transcription unit is high except for regions located at: (1) the untranslated leaders of the 1.2-kb mRNAs; (2) the N termini of the polypeptides specified by the HSV-2/HSV-1 1.2-kb mRNAs; (3) the intergenic region beyond the 3' co termini. Regions (2) and (3) are located within a transforming fragment of HSV-2. The possible significance of these data for HSV-mediated cell transformation is discussed.


Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons.
By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS) parvalbumin-positive interneurons of the striatum. Lack of receptor- and isoform-specific pharmacological agents, however, has hampered the progress toward a detailed identification of the specific DA receptors involved in these actions. To overcome this issue, in the present study we used four different mutant mice in which the expression of specific DA receptors was ablated. In D1 receptor null mice, D1R-/-, DA dose-dependently depolarized both LA and FS interneurons. Interestingly, SCH 233390 (10 microm), a D1-like (D1 and D5) receptor antagonist, but not l-sulpiride (3-10 microm), a D2-like (D2, D3, D4) receptor blocker, prevented this effect, implying D5 receptors in this action. Accordingly, immunohistochemical analyses in both wild-type and D1R-/- mice confirmed the expression of D5 receptors in both cholinergic and parvalbumin-positive interneurons of the striatum. In mice lacking D2 receptors, D2R-/-, the DA-dependent inhibition of GABA transmission was lost in both interneuron populations. Both isoforms of D2 receptor, D2L and D2S, were very likely involved in this inhibitory action, as revealed by the electrophysiological analysis of the effect of the DA D2-like receptor agonist quinpirole in two distinct mutants lacking D2L receptors and expressing variable contents of D2S receptors. The identification of the receptor subtypes involved in the actions of DA on different populations of striatal cells is essential to understand the circuitry of the basal ganglia and to develop pharmacological strategies able to interfere selectively with specific neuronal functions.


Induction of PAH-catabolism in mushroom compost and its use in the biodegradation of soil-associated phenanthrene.
This paper describes the induction of phenanthrene-catabolism within Phase II mushroom compost resulting from its incubation with (1) phenanthrene, and (2) PAH-contaminated soil. Respirometers measuring mineralization of freshly added 14C-9-phenanthere were used to evaluate induction of phenanthrene-catabolism. Where pure phenanthrene (spiked at a concentration of 400 mg kg(-1) wet wt.) was used to induce phenanthrene-catabolism in compost, induction was measurable, with maximal mineralization observed after 7 weeks phenanthrene-compost contact time. Where PAH-contaminated soil was used to induce phenanthrene-catabolism in un-induced compost, induction was observed after 5 weeks soil-compost contact time. Microcosm-scale amelioration of soil contaminated with 14C-phenanthrene (aged in soil for 516 days prior to incubation with compost) indicated that both induced (using pure phenanthrene) and uninduced Phase II mushroom composts were equally able to promote degradation of this soil-associated contaminant. After 111 days incubation time, 42.7 +/- 6.3% loss of soil-associated phenanthrene was observed in the induced-compost soil mixture, while 36.7 +/- 2.9% loss of soil-associated phenanthrene was observed in the uninduced-compost soil mixture. These results are notable as they indicate that while pre-induction of phenanthrene-catabolism within compost is possible, it does not significantly increase the extent of degradation when the compost is used to ameliorate phenanthrene-contaminated soil. Thus, compost could be used directly in the amelioration of contaminated land i.e. without pre-induction of catabolism.


An intron nucleotide sequence variant in a cloned beta +-thalassaemia globin gene.
A 7.5 kb Hsu I restriction fragment of genomic DNA containing a beta-globin gene has been isolated from a patient doubly heterozygous for beta + thalassaemia and a delta beta (Lepore globin fusion gene. This fragment must be derived from the chromosome carrying the beta +-thalassaemia determinant. The gross structure of the cloned gene plus flanking sequences is indistinguishable from that of a normal beta-globin gene. Within in 1606 base-pair transcribed region of the gene there is only one nucleotide difference from the normal beta-globin gene sequence. This is a G leads to A replacement 21 nucleotides upstream from the 3' terminus of the small intron. This nucleotide lies within a 10 base-pair sequence repeated in an inverted configuration near the 5' terminus of the small intron. The nucleotide replacement may result in a precursor mRNA less amenable to RNA splicing than its normal counterpart.


Chondrocyte-derived apoptotic bodies and calcification of articular cartilage.
Chondrocytes exposed to nitric oxide (NO) or antibody to Fas undergo cell death by apoptosis. This study examines structural and functional properties of chondrocyte-derived apoptotic bodies. In NO treated cartilage, the dense pericellular matrix that normally surrounds the cells is degraded and apoptotic bodies accumulate within and in the vicinity of the chondrocyte lacunae. Functional analysis shows that apoptotic bodies isolated from NO-treated chondrocytes or cartilage produce pyrophosphate. The levels of pyrophosphate produced by apoptotic bodies are increased by pretreatment of the chondrocytes with transforming growth factor beta and decreased by interleukin 1. Apoptotic bodies contain alkaline phosphatase and NTP pyrophosphohydrolase activities and can precipitate calcium. These results suggest that chondrocyte-derived apoptotic bodies express functional properties that may contribute to the pathologic cartilage calcification observed in aging and osteoarthritis.


Microbial Degradation of Polyhydroxyalkanoates with Different Chemical Compositions and Their Biodegradability.
The study addresses degradation of polyhydroxyalkanoates (PHA) with different chemical compositions-the polymer of 3-hydroxybutyric acid [P(3HB)] and copolymers of P(3HB) with 3-hydroxyvalerate [P(3HB/3HV)], 4-hydroxybutyrate [P(3HB/4HB)], and 3-hydroxyhexanoate [P(3HB/3HHx)] (10-12 mol%)-in the agro-transformed field soil of the temperate zone. Based on their degradation rates at 21 and 28 °C, polymers can be ranked as follows: P(3HB/4HB) > P(3HB/3HHx) > P(3HB/3HV) > P(3HB). The microbial community on the surface of the polymers differs from the microbial community of the soil with PHA specimens in the composition and percentages of species. Thirty-five isolates of bacteria of 16 genera were identified as PHA degraders by the clear zone technique, and each of the PHA had both specific and common degraders. P(3HB) was degraded by bacteria of the genera Mitsuaria, Chitinophaga, and Acidovorax, which were not among the degraders of the three other PHA types. Roseateles depolymerans, Streptomyces gardneri, and Cupriavidus sp. were specific degraders of P(3HB/4HB). Roseomonas massiliae and Delftia acidovorans degraded P(3HB/3HV), and Pseudoxanthomonas sp., Pseudomonas fluorescens, Ensifer adhaerens, and Bacillus pumilus were specific P(3HB/3HHx) degraders. All four PHA types were degraded by Streptomyces.


Outcome of lateral retinacular nerve transection combined with release for recalcitrant iliotibial band friction syndrome.
In this retrospective study, a technique consisting in neurolysis of the lateral retinacular nerve combined with a partial release through elliptic excision of the iliotibial band (ITB) is evaluated for efficacy in recalcitrant ITB friction syndrome and compared with results from other techniques reported in literature. From April 2014 to December 2017, 21 patients suffering from recalcitrant ITB friction syndrome were surgically treated with the aforementioned technique. 15 patients (15 knees) were available for a written retrospective reassessment after completion of a follow-up period of at least 12 months. Residual pain was scored using the Visual Analogue Scale (VAS). The functional outcome was evaluated by two patient reported outcome measurement scales (PROMs), the Lysholm and the International Knee Documentation Committee (IKDC) score. Return to sport was analysed by duration of the inactivity period as well as by the Tegner score. Overall satisfaction was evaluated using a modified Boyden scale. At final follow-up of one year, the performed intervention resulted in a pain reduction (VAS 4.2 (1-8) to 1.4 (0-6)) and improved knee function (Lysholm 59.53 to 87.73, IKDC 75) with return to sport (Tegner 4.3 to 5.4) after a median of 23.8 weeks (6 to 52). Twelve patients reported good or excellent results (80%) at final follow-up, and 12 patients (80%) would undergo surgery again, if necessary. The treatment of recalcitrant ITB friction syndrome by combining neurectomy of the lateral retinacular nerve with elliptic excision of the ITB resulted in good to excellent results in 80% of treated cases with return to sport in 93%.


Analysis of genomic rearrangements associated with EGRFvIII expression suggests involvement of Alu repeat elements.
We have developed a polymerase chain reaction (PCR)-based strategy for the synthesis and analysis of rearranged epidermal growth factor receptor (EGFR) fragments associated with the vIII mutant receptor expressed in glioblastomas with EGFR amplification. The sequencing of aberrant tumor fragments showed that intragenic deletion rearrangements consistently involve an approximately 600-bp region in intron 7 of EGFR and several rearrangement sites interspersed throughout the large (>100 kb) first intron of this gene. Examination of the intron 7 breakpoint region revealed an Alu repeat element, and all intron 7 rearrangement sites were located within or downstream of this repeat sequence. Analysis of intron 1 for similar sequences resulted in the identification of 11 sites containing >80% homology with parts of the Alu element in intron 7. Reverse transcriptase-PCR and/or Western analysis of the tumors showed the presence of EGFRvIII cDNAs and/or proteins, respectively, in all cases for which a rearranged genomic fragment was generated by long-range PCR. Collectively, these data suggest that EGFR rearrangements, associated with the synthesis of the most common EGFR mutant, are mediated by a specific sequence element.


The Influence of pCO2-Driven Ocean Acidification on Open Ocean Bacterial Communities during A Short-Term Microcosm Experiment in the Eastern Tropical South Pacific (ETSP) off Northern Chile.
Due to the increasing anthropogenic CO2 emissions, Ocean Acidification (OA) is progressing rapidly around the world. Despite the major role that microorganisms play on the marine biogeochemical cycling and ecosystem functioning, the response of bacterial communities upon OA scenarios is still not well understood. Here, we have conducted a detailed characterization of the composition and relative abundance of bacterial communities in the water column of an open-ocean station in the Eastern Tropical South Pacific (ETSP) off northern Chile and their interactions with environmental factors. In addition, through a short-term microcosm experiment, we have assessed the effect of low pH/high pCO2 conditions over the abundance and genetic diversity of bacterial communities. Our results evidence a clear partitioning of community composition that could be attributed mostly to dissolved oxygen. However, our experimental approach demonstrated that low pH/high pCO2 conditions might modify the structure of the bacterial community, evidencing that small changes in pH may impact significantly the abundance and diversity of key microorganisms. This study constitutes a first step aiming to provide insight about the influence of changing carbonate chemistry conditions on natural bacterial communities and to shed light on the potential impact of OA in biogeochemical cycles on the ETSP region.


Identifying nonlinear dynamical systems via generative recurrent neural networks with applications to fMRI.
A major tenet in theoretical neuroscience is that cognitive and behavioral processes are ultimately implemented in terms of the neural system dynamics. Accordingly, a major aim for the analysis of neurophysiological measurements should lie in the identification of the computational dynamics underlying task processing. Here we advance a state space model (SSM) based on generative piecewise-linear recurrent neural networks (PLRNN) to assess dynamics from neuroimaging data. In contrast to many other nonlinear time series models which have been proposed for reconstructing latent dynamics, our model is easily interpretable in neural terms, amenable to systematic dynamical systems analysis of the resulting set of equations, and can straightforwardly be transformed into an equivalent continuous-time dynamical system. The major contributions of this paper are the introduction of a new observation model suitable for functional magnetic resonance imaging (fMRI) coupled to the latent PLRNN, an efficient stepwise training procedure that forces the latent model to capture the 'true' underlying dynamics rather than just fitting (or predicting) the observations, and of an empirical measure based on the Kullback-Leibler divergence to evaluate from empirical time series how well this goal of approximating the underlying dynamics has been achieved. We validate and illustrate the power of our approach on simulated 'ground-truth' dynamical systems as well as on experimental fMRI time series, and demonstrate that the learnt dynamics harbors task-related nonlinear structure that a linear dynamical model fails to capture. Given that fMRI is one of the most common techniques for measuring brain activity non-invasively in human subjects, this approach may provide a novel step toward analyzing aberrant (nonlinear) dynamics for clinical assessment or neuroscientific research.


Intramembrane charge movement associated with endogenous K+ channel activity in HEK-293 cells.
1. The use of molecular biology in combination with electrophysiology in the HEK-293 cell line has given fascinating insights into neuronal ion channel function. Nevertheless, to fully understand the properties of channels exogenously expressed in these cells, a detailed evaluation of endogenous channels is indispensable. 2. Previous studies have shown the expression of endogenous voltage-gated K+, Ca2+, and Cl- channels and this predicts that changes in membrane potential will cause intramembrane charge movement, though this gating charge translocation remain undefined. Here, we confirm this prediction by performing patch-clamp experiments to record ionic and gating currents. Our data show that HEK-293 cells express at least two types of K+-selective endogenous channels which sustain the majority of the ionic current, and exclude a significant contribution from Ca2+ and Cl- channels to the whole-cell current. 3. Gating currents were unambiguously resolved after ionic current blockade enabling this first report of intramembrane charge movement in HEK-293 cells arising entirely from endogenous K+ channel activity, and providing valuable information concerning the activation mechanism of voltage-gated K+ channels in these cells.