Escherichia albertii EA046 (O9) harbors two polysaccharide gene clusters for synthesis of the O-antigen by the Wzx/Wzy-dependent pathway and a mannan shared by Escherichia coli O8 by the Wzm/Wzt-dependent pathway.
O antigen is a polysaccharide chain of a lipopolysaccharide on the outer membrane of Gram-negative bacteria. O-antigen-based serotyping and molecular typing are widely used for epidemiological and surveillance purposes. Two polysaccharides were isolated by Sephadex G-50 gel-permeation chromatography following mild acid degradation of the lipopolysaccharide of Escherichia albertii EA046 assigned to serotype O9. The polysaccharide eluted first was considered as the O-antigen. It was composed of tetrasaccharide repeating units containing two residues of d-Man and one residue each of d-Gal and d-GlcNAc as well as glycerol phosphate. It had the following unique structure which was established by NMR spectroscopy applied to the initial and dephosphorylated polysaccharides: The polysaccharide eluted from the gel second was identified as a mannan with a → 3)-β-d-Manp-(1 → 2)-α-d-Manp-(1 → 2)-α-d-Manp-(1 → trisaccharide repeating unit. In E. albertii EA046, two polysaccharide gene clusters were found at a chromosomal locus flanked by the conserved galF gene and the histidine synthesis operon (his). They were suggested to drive the biosynthesis of the O-antigen by the Wzy/Wzy-dependent pathway and the mannan by the Wzm/Wzt-dependent pathway. The mannan shares the structure and gene cluster with a polysaccharide isolated earlier from the lipopolysaccharide of Escherichia coli O8.


Age-related cholinergic drug effects on analgesia in two inbred strains of mice.
The two inbred strains of mice C57BL/6 and DBA/2 are characterized by a different behavioral reactivity to cholinergic agents during development. The present experiment revealed that the strain-dependent differences in cholinergic-mediated analgesia during development disappeared during adult life. In fact, oxotremorine administration (0.0025 and 0.005 mg/kg) exerted the same analgesic effect in both strains at 6 months of age, in contrast with the finding of the lack of any effect of the drug in C57 mice at two months of age in comparison with DBA.


MRI biosensor for protein kinase A encoded by a single synthetic gene.
Protein kinases including protein kinase A (PKA) underlie myriad important signaling pathways. The ability to monitor kinase activity in vivo and in real-time with high spatial resolution in genetically specified cellular populations is a yet unmet need, crucial for understanding complex biological systems as well as for preclinical development and screening of novel therapeutics. Using the hypothesis that the natural recognition sequences of protein kinases may be detected using chemical exchange saturation transfer magnetic resonance imaging, we designed a genetically encoded biosensor composed of eight tandem repeats of the peptide LRRASLG, a natural target of PKA. This sensor displays a measurable change in chemical exchange saturation transfer signal following phosphorylation by PKA. The natural PKA substrate LRRASLG exhibits a chemical exchange saturation transfer-magnetic resonance imaging contrast at +1.8 and +3.6 ppm, with a >50% change after phosphorylation with minutes-scale temporal resolution. Expression of a synthetic gene encoding eight monomers of LRRASLG yielded two peaks at these chemical exchange saturation transfer frequencies. Taken together, these results suggest that this gene may be used to assay PKA levels in a biologically relevant system. Importantly, the design strategy used for this specific sensor may be adapted for a host of clinically interesting protein kinases.


Providing distinct vergence and version dynamics in a bilateral oculomotor network.
Given reported interactions between vergence and version dynamics, ocular reflexes cannot be properly modelled as separate independent subsystems. Using a model structure compatible with known anatomy, we show that a single bilateral system can produce results consistent with observed data both at the central and ocular levels. This model provides for both vergence and conjugate integrators in a single controller, and explains the observed modulation on abducens interneurons and mesencephalic vergence cells during vergence responses. Reported interactions between version and vergence would then be a natural consequence of a shared premotor network. Major implications include: the need to record both eyes in a protocol, since cross-talk is always possible; and adaptation to monocular changes could be distributed in all motor projections to both eyes.


Post mortem recovery of mandibular osseous graft with cellulose acetate filter. A case report.
A surgical procedure was performed to re-establish both aesthetics and functional form to a post partial mandibulectomy patient. A particulate, autogenous osseous graft from the hip was supported by a mandibular tantalum splint lined with a cellulose acetate filter. The patient developed metastatic carcinoma in the donor graft site and lung. The mandibular graft and supporting tissue was removed postmortem and examined histologically. It was observed that normal bone reconstruction was taking place and that union of mandibular bone and graft was evident. Secondary squamous cell carcinoma had invaded the symphysis area of the graft. It is also of interest to note that the tumour was mot able to penetrate those areas where the cellulose acetate filter was present.


Effects of bioactive components of Pu-erh tea on gut microbiomes and health: A review.
Pu-erh tea is a post-fermentation tea with unique flavor and multiple health benefits. Due to the various microorganisms involved in the post-fermentation process, Pu-erh tea contains highly complex components, which have rich interactions with the gut microbiomes (GMs). Because the structure and homeostasis of GMs are closely related to human wellness and the various diseases progress, the beneficial effects of Pu-erh tea on GMs have a great potential for application in health care. However, there is no systematic summary of the bioactive components of Pu-erh tea, and their effects on the GMs. Here, we review the current studies on the effects of Pu-erh tea and its bioactive components on the structure of GMs as well as on health improvement, and further discuss the relevant quality indicators. This "components - function - indicators" clue will hopefully stimulate the standardization of Pu-erh tea fermentation process and the development of its functional products.


COVID-19: a primer for the rheumatologist: management of patients and care settings.
There are currently many unanswered questions surrounding the management of patients with immune-mediated inflammatory diseases during the COVID-19 pandemic and several 'rapid' guidelines have been released, although are subject to be updated and changed in the near future. The purpose of this review is to discuss the approach to management of patients with immune-mediated diseases during the COVID-19 pandemic. At present, there is little evidence to suggest an increased risk of COVID-19 infection or its complications in patients with immune-mediated diseases or associated with conventional or biologic disease modifying antirheumatic drugs; however, glucocorticoid use does appear to have negative associations. Currently, conventional and biologic disease modifying antirheumatic drugs can be continued in the absence of SARS-CoV-2 exposure. In the case of exposure, with the exception of hydroxyhcloroquine and sulfasalazine, immunosuppression should be held for 2 weeks. Our recommendations and the guidelines we discuss here are based on C-level recommendations but help provide a framework for how to counsel our patients during this pandemic.


[The de-epidermized sural flap: An original technique to increase the reliability of the neurocutaneous sural flap].
The neurocutaneous sural flap is useful to cover defects of the distal quarter of the lower limb. Nevertheless, severe complications occur in 14% of the cases, and venous congestion is reported in 75% of these cases. This congestion can lead to total necrosis of the flap and a failure of the procedure. We describe a new surgical method aiming to reduce the risk of venous congestion occurrence and failure of the defect coverage. We realized a retrospective study of patients who undergone a de-epidermized distally based neurocutaneous sural flap in our surgery department from 2015 to 2020. The following data were collected: sex, age, vascular risk factors, size of the wound, defect area, etiology, delay between the surgery of the flap and the split-thickness skin graft and complications. The cohort is composed of 5 cases. We reported no failure of the coverage of the defect. There were no cases of venous congestion. The de-epidermized distally based neurocutaneous sural flap could increase the reliability of these flaps by reducing the risk of venous congestion. A larger study comparing the classic technique to the de-epidermized sural flap could confirm these data on a greater number of cases and position this technique in the therapeutic arsenal.


Sequestration of strontium, nickel, and cadmium on glomalin-related soil protein: Interfacial behaviors and ecological functions.
Glomalin-related soil protein (GRSP) is a widespread recalcitrant soil protein complex that promotes the immobilization of metals in soils. Herein, we combined indoor simulation and field investigation to reveal the interfacial behaviors and ecological functions of GRSP to the three typical metals (Sr(II), Ni(II), and Cd(II)). The kinetic and isotherm data suggested that GRSP had a strong ability to adsorb the metals, which was closely related to the Hard-Soft-Acid-Base theory and the film diffusion mechanisms. Regarding environmental factors, the higher solution pH was beneficial to the adsorption of the metals onto GRSP, while the adsorption capacity decreased at lower or higher salinity due to the salting-out and Na+ competition effects. Moreover, Sr(II), Ni(II), and Cd(II) showed competitive adsorption onto GRSP, which was associated with the spatial site resistance effect. By comparing the retention factors of seven natural and artificial particles, GRSP had elevated distribution coefficients in high metal concentration, while its retention factors showed a relatively lower decrease, suggesting that GRSP had excellent buffer performance for a potential metal pollution emergency. Through the continental-scale coastal regions investigation, GRSP sequestered 1.05-3.11 μmol/g Ni, 0.31-1.49 μmol/g Sr, and 0.01-0.06 μmol/g Cd with 0.54-0.91 % of the sediment mass, demonstrating its strong ability to adsorb the metals. Therefore, we advocate that GRSP, as a recalcitrant protein complex, can be considered an effective tool for buffering capacity of metal pollution and environmental capacity within coastal wetlands.


Integrative, multi-omics, analysis of blood samples improves model predictions: applications to cancer.
Cancer genomic studies often include data collected from several omics platforms. Each omics data source contributes to the understanding of the underlying biological process via source specific ("individual") patterns of variability. At the same time, statistical associations and potential interactions among the different data sources can reveal signals from common biological processes that might not be identified by single source analyses. These common patterns of variability are referred to as "shared" or "joint". In this work, we show how the use of joint and individual components can lead to better predictive models, and to a deeper understanding of the biological process at hand. We identify joint and individual contributions of DNA methylation, miRNA and mRNA expression collected from blood samples in a lung cancer case-control study nested within the Norwegian Women and Cancer (NOWAC) cohort study, and we use such components to build prediction models for case-control and metastatic status. To assess the quality of predictions, we compare models based on simultaneous, integrative analysis of multi-source omics data to a standard non-integrative analysis of each single omics dataset, and to penalized regression models. Additionally, we apply the proposed approach to a breast cancer dataset from The Cancer Genome Atlas. Our results show how an integrative analysis that preserves both components of variation is more appropriate than standard multi-omics analyses that are not based on such a distinction. Both joint and individual components are shown to contribute to a better quality of model predictions, and facilitate the interpretation of the underlying biological processes in lung cancer development. In the presence of multiple omics data sources, we recommend the use of data integration techniques that preserve the joint and individual components across the omics sources. We show how the inclusion of such components increases the quality of model predictions of clinical outcomes.


BBS4 protein has basal body/ciliary localization in sensory organs but extra-ciliary localization in oligodendrocytes during human development.
Bardet-Biedl syndrome protein 4 (BBS4) localization has been studied in human embryos/fetuses from Carnegie stage 15 to 37 gestational weeks in neurosensory organs and brain, underlying the major clinical signs of BBS. We observed a correlation between the differentiation of the neurosensory cells (hair cells, photoreceptors, olfactory neurons) and the presence of a punctate BBS4 immunostaining in their apical cytoplasm. In the brain, BBS4 was localized in oligodendrocytes and myelinated tracts. In individual myelinated fibers, BBS4 immunolabelling was discontinuous, predominantly at the periphery of the myelin sheath. BBS4 immunolabelling was confirmed in postnatal developing white matter tracts in mouse as well as in mouse oligodendrocytes cultures. In neuroblasts/neurons, BBS4 was only present in reelin-expressing Cajal-Retzius cells. Our results show that BBS4, a protein of the BBSome, has both basal body/ciliary localization in neurosensory organs but extra-ciliary localization in oligodendrocytes. The presence of BBS4 in developing oligodendrocytes and myelin described in the present paper might attribute a new role to this protein, requiring further investigation in the field of myelin formation.


An enzyme-linked immunosorbent assay for antistriational antibodies associated with myasthenia gravis and thymoma: comparison with indirect immunofluorescence.
Autoantibodies to the striations of skeletal muscle (AStrA) detected by immunofluorescence are useful in the diagnosis of a thymoma associated with myasthenia gravis (MG). With the intention of developing a better method, an enzyme-linked immunosorbent assay (ELISA) has been evaluated in 147 MG patients and 200 healthy controls. An additional 107 patients with various autoimmune diseases and autoantibodies were also tested. With a crude actomyosin preparation, the ELISA gave similar results to immunofluorescence, viz. positives in 42% of MG patients, but in all with a histologically proven thymoma. Less than 1% of the healthy controls were positive but false positives were found in patients with liver disease and anti-smooth muscle antibodies. After treatment of rheumatoid arthritis with D-penicillamine the titre of AStrA may rise. The ELISA was shown to be sensitive and reproducible, but immunofluorescence is a more practical method of distinguishing between the different categories of anti-muscle antibodies. ELISA should prove particularly useful for quantitation and sequential monitoring.


Effects of selective neurotoxic lesion of lumbosacral serotonergic and noradrenergic systems on autotomy behaviour in rats.
Male rats underwent unilateral ligation and transection of the sciatic and saphenous nerves 2, 7 or 14 days after being injected intrathecally (at the thoracolumbar junction) with 6-hydroxydopamine (6-OHDA), 5,6-dihydroxytryptamine (5,6-DHT) or vehicle, and the development of autotomy was monitored. The effects of both neurotoxins on cervicothoracic (C5-T1) and lumbosacral (L1-S1) norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) spinal cord levels were analysed by HPLC in separate groups of rats. 6-OHDA treatment (20 micrograms/10 microliters) produced a rapid (from day 2) and significant (90-95%) fall in NE content only at L1-S1. 5,6-DHT administration (20 micrograms/10 microliters) produced a gradual (68%, 90% and 94%, at 2, 7 and 14 days, respectively) and selective depletion of 5-HT only at L1-S1. DA levels remained essentially unchanged after both neurotoxins. No differences in monoamine levels were detected among groups injected with vehicle. The main effects of neurotoxins on autotomy were: (1) a significant delay in the onset of autotomy in the rats injected with 6-OHDA 2 days before neurectomy; (2) a trend to autotomize earlier and more severely in the rats injected with 5,6-DHT 7 days before neurectomy and (3) an almost complete suppression of autotomy in the rats injected with 5,6-DHT 14 days before neurectomy. These results revealed that the expression of autotomy in rats can be modulated by interfering with spinal cord serotonergic activity and suggest new possible avenues for the treatment of certain specific pain diseases, such a phantom limb pain, by using selective agents capable of activating or blocking spinal cord serotonergic receptor subtypes.


Assessment of genetic diversity and phylogenetic relationship among grouper species Epinephelus spp. from the Saudi waters of the Arabian Gulf.
Understanding of fish genetic characterization plays a vital role in the conservation and utilization of fish genetic resources of grouper species. The present study was carried out to assess the genetic diversity and phylogenetic relationships in five grouper species, Epinephelus spp. from eastern Saudi Arabian coast using two molecular marker systems, inter simple sequence repeat (ISSR) and microsatellite (SSR) markers. In total, 219 individuals grouper specimens (Epinephelus tauvina, E. coioides, E. bleekeri, E. malabaricus, and E. areolatus) were genotyped with 10 ISSR and 11 SSR selected primers. The ISSR produced 94 DNA fragments, of which 44 were polymorphic with an average of 2.13 fragment per primer. While SSR primers generated 107 alleles, all of them were polymorphic with an average 9.72 per primer. ISSR and SSR techniques demonstrated a high level of gene diversity and genetic distances illustrated by UPGMA dendrograms among the grouper species. The results proved that the SSR markers were highly informative and efficient in detecting genetic variability and relationships of the Epinephelus spp.


The effect of blockade of kappa-opioid receptors in the medial preoptic area on the luteinizing hormone surge in the proestrous rat.
The present study examined whether blockade of kappa-opioid receptors in the medial preoptic area (MPOA) prior to the critical period on the afternoon of proestrus could prematurely evoke an ovulatory luteinizing hormone (LH) surge, and if so, whether norepinephrine (NE) is involved in mediating this response. In the first experiment, push-pull perfusion of the MPOA with nor-binaltorphimine (nor-BNI), a specific kappa-opioid receptor antagonist, was done in rats between 10.30 and 13.50 h on proestrus. To determine whether any resulting ovulation was due to a nor-BNI-induced increase in LH release, rats were injected with pentobarbital at 13.55 h to block the afternoon LH surge. In 7 of 10 rats, nor-BNI in the MPOA produced a large increase in LH release beginning between 12.30 and 13.30 h, and 5 of 7 ovulated. During MPOA perfusion with cerebrospinal fluid in our normal colony between 14.00 and 17.00 h, surges of LH release began in the majority of rats between 15.30 and 16.30 h. Thus blockade of MPOA kappa-opioid receptors advanced the LH surge by 3 h. The next experiment examined the effect of NE synthesis inhibition with bis(4-methyl-1-homopiperazinylthiocarbonyl) disulfide (FLA-63), or alpha-adrenergic receptor blockade with phenoxybenzamine (PBZ), on the nor-BNI-induced LH response. In 5 of 6 vehicle-treated rats, blockade of MPOA kappa-opioid receptors elicited a large increase in LH release and all 5 ovulated. In contrast, only 3 of 8 rats pretreated with FLA-63 had a large increase in LH release and ovulated, and PBZ prevented the nor-BNI-induced LH increase and ovulation in 4 of 4 rats. PBZ also prevented the afternoon LH surge and ovulation in 4 of 4 rats in our normal colony. Finally, HPLC measurement of NE levels in MPOA push-pull perfusate indicated no increase in NE release during the nor-BNI-induced or normal afternoon LH surges. These results indicate that antagonism of kappa-opioid receptors in the MPOA can prematurely evoke an ovulatory LH surge prior to the critical period on the afternoon of proestrus. Furthermore, the nor-BNI-induced as well as the normal afternoon LH surges are dependent on the proper functioning of central noradrenergic neurons, but do not involve increased NE release within the MPOA.


Addressing policy barriers to paternal involvement during pregnancy.
Efforts to reduce infant mortality in the United States have failed to incorporate paternal involvement. Research suggests that paternal involvement, which has been recognized as contributing to child development and health for many decades, is likely to affect infant mortality through the mother's well-being, primarily her access to resources and support. In spite of that, systemic barriers facing the father and the influence on his involvement in the pregnancy have received little attention. The Commission on Paternal Involvement in Pregnancy Outcomes (CPIPO) has identified the most important social barriers to paternal involvement during pregnancy and outlined a set of key policy priorities aimed at fostering paternal involvement. This article summarizes the key recommendations, including equitable paternity leave, elimination of marriage as a tax and public assistance penalty, integration of fatherhood initiatives in MCH programs, support of low-income fathers through employment training, father inclusion in family planning services, and expansion of birth data collection to include father information.


Long-term follow-up of children and adolescents diagnosed with hypertrophic cardiomyopathy: risk factors for adverse arrhythmic events.
Our aim was to identify prognostic factors for an arrhythmic event (AE) in children with hypertrophic cardiomyopathy (HCM) without a previous AE. One hundred thirty-one nonconsecutive patients (≤ 20 years) with HCM but no previous AE were evaluated at the NIH Clinical Center from 1980 to 2001. At a median follow-up of 6.4 years, 22 patients experienced an AE [sudden death (SD) (n = 12), resuscitated cardiac arrest (n = 3), clinical sustained ventricular tachycardia (VT) (n = 2), and implantable cardiac defibrillator discharge (n = 5)], resulting in a 2% annual AE rate. Baseline factors that were most predictive in univariate risk analysis included ventricular septal thickness (ST) (P = 0.01), VT induction by programmed ventricular stimulation (PVS) (P = 0.01), age (P = 0.05), and presyncope/syncope (P = 0.05). In multivariate analysis, ST, age, presyncope/syncope, and PVS were not independently predictive of risk for an AE. However, the 5-year event rates for AE was 15% (95% CI: 5-23%) if ST ≥ 20 mm, 19% (95% CI: 6-31%) when age ≥ 13 years and ST ≥ 20 mm were combined together, and 23% (95% CI: 3-39%) when PVS and ST ≥ 20 mm were combined together. Of the various risk factors that were considered in our pediatric HCM cohort, ST and inducible VT were the most significant univariate predictors of risk for an AE. More traditional risk factors identified in older patients (family history of SD, VT on Holter, and exercise-induced hypotension) were not predictive of an AE in patients age under 21 years.


Risk factors predisposing to psychotic symptoms during levetiracetam therapy: A retrospective study.
While levetiracetam (LEV) usage is a known risk factor for psychosis in epilepsy, the modulating effect of certain patient and treatment characteristics on the risk of psychosis has yet to be fully elucidated. In our tertiary epilepsy center, 84 patients with psychotic symptoms during LEV usage and 100 controls without psychotic symptoms during LEV usage were selected. Patient records were reviewed including demographics, medical history, antiepileptic drug use, and cognitive abilities. Univariate comparisons were performed, and variables with p < 0.1 were selected for binary logistic regression analysis. The total incidence of psychosis during LEV therapy in our population was 3.7%. The timing of psychotic symptoms was classified as postictal in 20 (19.8%), interictal in 14 (15.4%), postepilepsy surgery in 1 (1.1%), and unknown in 18 cases (19.8%). In 31 cases (34.1%), psychotic symptoms were classified as an antiepileptic drug-induced psychotic disorder (AIPD) as a result of LEV. In 7 cases (7.7%), AIPD occurred as a result of a different antiepileptic drug. A significant association was found between the experience of psychotic symptoms and status epilepticus (p = 0.002), a history of psychotic symptoms (p < 0.000), a history of psychiatric illness other than psychosis (p = 0.010), and concomitant phenytoin (PHT) usage (p = 0.044). Cotherapy with lamotrigine (LTG) was protective (p = 0.042). A separate analysis of controls and exclusively the 31 cases with LEV-induced AIPD yielded comparable results; a significant association was confirmed with status epilepticus (p = 0.021) and history of psychotic symptoms (p = 0.018), as well as with female gender (p = 0.047) and intellectual disability (p = 0.043). Our retrospective study found that psychotic symptoms during LEV therapy were significantly associated with status epilepticus, a history of psychotic symptoms, a history of psychiatric illness other than psychosis, and concomitant PHT usage, whereas concomitant LTG usage was protective. Psychotic symptoms specifically as an adverse drug reaction to LEV were significantly associated with female gender, intellectual disability, status epilepticus, and a history of psychotic symptoms.


Palbociclib (PD 0332991) Interaction with Kinases. Theoretical and Comparative Molecular Docking Study.
The optimized geometry of palbociclib, (PD 0332991) (8-cyclopentyl-6-ethanoyl-5-methyl-2-(5-(piperazin-1-yl)pyridin-2-ylamino)pyrido[2,3-d]pyrimidin-7(8H)-one), electrostatic potential map, molecular orbitals were calculated using the density functional theory. The geometry was used in a molecular docking study of palbociclib-kinase complexes, results could be explained by the charge of the nitrogen and oxygen atoms within the palbociclib. Energy gap of HOMO-LUMO surfaces, could help to explain the reactivity of the ligand and the hydrogen bonding with three different kinases, two of CDK6 and one of CDK4 type. Docking results are similar and complementary with literature reports using molecular dynamics, were hydrogen bonding was obtained and analyzed. The promiscuity of three kinases with palbociclib was detected by the docking results, thus, palbociclib could be used in other types of cancer besides myeloid leukemia. Some similarities are found with CDK4/CDK6 kinases which allow us to determine that palbociclib could be used to control other resistant inhibitor types of cancer.


Revealing empirical association among ecological footprints, renewable energy consumption, real income, and financial development: a global perspective.
This study quantifies the effect of real income, financial development, trade openness, and renewable energy consumption on the ecological footprint (EFP) of consumption for a panel data of 152 economies during the period 1990-2017. Several panel unit root tests validate that datasets are stationary. The findings from the Westerlund co-integration test depict that variables are co-integrated. The augmented mean group panel algorithm method is then applied to measure the long-run linkage between variables. The analysis outcomes show a negative and significant association between the EFP and real income per capita in the case of the higher-income group while remaining groups depict the other way round relationship. Further, openness and renewable energy consumption are also observed to reduce EFP in the groups of higher-income and upper-middle-income economies. Finally, financial development is observed to lessen environmental degradation in the case of the higher-income group. Similarly, the results of the Granger causality test based on the Dumitrescu-Hurlin panel provided evidence of varied causality relationship among the variables in different income groups. In addition, we also surpassed an impulse response and variance decomposition analysis that permitted to forecast the impact of concerned variables on environmental degradation during the selected period. Finally, the findings from the empirical analysis suggest that per capita economic growth will have an increasing effect on the EFP for the concerned income group except for higher-income countries in the future.


Enhancing community disaster resilience through mass sporting events.
Disaster response requires rapid, complex action by multiple agencies that may rarely interact during nondisaster periods. Failures in communication and coordination between agencies have been pitfalls in the advancement of disaster preparedness. Recommendations of the Federal Emergency Management Agency address these needs and demonstrate commitment to successful disaster management, but they are challenging for communities to ensure. In this article we describe the application of Federal Emergency Management Agency guidelines to the 2008 and 2009 Chicago Marathon and discuss the details of our implementation strategy with a focus on optimizing communication. We believe that it is possible to enhance community disaster preparedness through practical application during mass sporting events.


20 years of functional treatment for clubfoot: advantages and limitations compared with the Ponseti method.
Currently, the Ponseti method has become the most popular technique for the management of congenital clubfoot. Besides this treatment, the functional method or the 'French method' (FFM) represents another treatment option. Throughout our study, we will describe this method, based on the 'Saint Vincent de Paul' protocol with some modifications that we bring progressively. Carried out over the last 20 years at our institution. In total 145 children (210 clubfeet) were treated using FFM. Our technique is based on the 'Saint Vincent de Paul' protocol from Paris. This method consists of daily manipulations of the feet by specialised physiotherapists associated with thermoformable orthotics devices. An evaluation of the patient at 5 year of age is performed. Gait analysis was introduced in 2011 as a complementary assessment tool. Less than 15% of the feet underwent a surgical procedure at walking age. Compliance to treatment was significantly higher than with the Ponseti method. At the last follow-up, 80% of the children had good to excellent results without major residual deformity. Totally 7% of the children required a later intervention either for recurrence or for major residual deformity. FFM is an alternative approach in the management of clubfoot that has proven to be successful due to the precision and modularity of its splinting system. Good compliance and low recurrence rate are other elements to consider. However, it requires a well-trained physical therapist. The main disadvantages of this method are the high cost compared to the Ponseti method and the difficulty of applying this method in developing countries.


Immunohistochemical identification of proteoglycan form of macrophage colony-stimulating factor on bone surface.
Several studies using op/op mice have shown that macrophage colony-stimulating factor (M-CSF) was necessary for osteoclast formation in vivo. Previously we reported that osteoblastic cells produced two molecular forms of M-CSF; one is an 85-kDa M-CSF, and the other is a proteoglycan form of M-CSF (PG-M-CSF) which has a binding affinity for bone-derived collagens and is extractable from human bone. In this study, we performed immunostaining of human bone using a newly established anti-PG-M-CSF antibody, and showed positive staining PG-M-CSF, probably produced by bone lining cells, on the bone surface. This observation suggests that the bone surface is suitable for osteoclast formation because of the presence of PG-M-CSF.


Effects of Natural and Synthetic Astaxanthin on Growth, Body Color, and Transcriptome and Metabolome Profiles in the Leopard Coralgrouper (Plectropomus leopardus).
Natural and synthetic astaxanthin can promote pigmentation in fish. In this study, the effects of dietary astaxanthin on growth and pigmentation were evaluated in leopard coralgrouper (Plectropomus leopardus). Fish were assigned to three groups: 0% astaxanthin (C), 0.02% natural astaxanthin (HP), and 0.02% synthetic astaxanthin (AS). Brightness (L*) was not influenced by astaxanthin. However, redness (a*) and yellowness (b*) were significantly higher for fish fed astaxanthin-containing diets than fish fed control diets and were significantly higher in the HP group than in the AS group. In a transcriptome analysis, 466, 33, and 32 differentially expressed genes (DEGs) were identified between C and HP, C and AS, and AS and HP, including various pigmentation-related genes. DEGs were enriched for carotenoid deposition and other pathways related to skin color. A metabolome analysis revealed 377, 249, and 179 differential metabolites (DMs) between C and HP, C and AS, and AS and HP, respectively. In conclusion, natural astaxanthin has a better coloration effect on P. leopardus, which is more suitable as a red colorant in aquaculture. These results improve our understanding of the effects of natural and synthetic astaxanthin on red color formation in fish.


Molecular Imaging of the Noradrenergic System in Idiopathic Parkinson's Disease.
Noradrenergic neurons in both the peripheral nervous system and in the central nervous system (CNS) undergo severe degeneration in patients with Parkinson's disease (PD). This loss of noradrenaline may play essential roles in the occurrence of a wide range of prevalent non-motor symptoms and can further complicate the lives of PD patients. In vivo molecular imaging of noradrenaline may provide insights into to the extent of degeneration of noradrenergic neurons and subsequent depletion of noradrenergic projections. Molecular imaging methods exist to quantify the noradrenergic deficiency in peripheral autonomic terminals, such as [123I]-meta-iodobenzylguanidin scintigraphy of the heart. However, the degeneration of noradrenergic nuclei in the brainstem and their projections to the CNS has only been quantified with non-selective positron emission tomography ligands in previous studies. Here, we review recent advances in in vivo molecular imaging techniques that evaluate the role of deficits of noradrenaline in PD patients in the manifestation of motor and non-motor symptoms.


Developmental neurotoxicity of chlorpyrifos: targeting glial cells.
The pesticide chlorpyrifos (CPF) causes neurobehavioral damage, even at doses that do not elicit acute cholinergic toxicity. CPF disrupts the developing brain during glial proliferation and differentiation. Since glial cells play critical roles in brain development and function, we hypothesized that CPF neurotoxicity involves alteration of glial cell development. CPF effects in C6 glioma cells mirrored effects in the intact brain: inhibited DNA synthesis; interfered with adenylyl cyclase (AC) signaling; obstructed DNA binding to transcription factors involved in cell differentiation; and enhanced reactive oxygen species (ROS) formation. CPF was administered to prenatal and neonatal rats and examined for markers of astrocytes, oligodendrocytes, and neurons. Widespread effects were elicited by exposure during the peak period of gliogenesis. Males were preferentially targeted during postnatal exposures while females experienced delayed effects following gestational exposure, commensurate with behavioral outcomes. Alterations in glial cell development contribute to CPF neurotoxicity, extending vulnerability to myelination, synaptic plasticity, and architectural modeling, which continue into adolescence.


Quantification of neutralizing anti-drug antibodies and their neutralizing capacity using competitive displacement and tandem mass spectrometry: Infliximab as proof of principle.
The development of anti-drug antibodies (ADA) in patients treated with therapeutic proteins can result in treatment failure. The clinically most relevant fraction of these antibodies are the neutralizing anti-drug antibodies (NAb) that block the pharmacological function of the drug. Consequently, the detection of NAb in plasma is a better predictor of loss of therapeutic response than increased levels of total anti-drug antibodies (ADA) test. Traditional assays to detect ADA and NAb have limited specificity, sensitivity and linear dynamic range. Here, we demonstrate for the first time the potential of a LC-MS/MS method to measure the concentration of NAb against therapeutic proteins in plasma as exemplified with infliximab (IFX). We designed a competitive screening assay in which the presence of NAb in patients plasma prevents the binding of stable isotopically labeled (SIL) mAb infliximab to TNF-α ligand fixed on a 96-well plate. After washing, eluting and digesting, the signal intensity of SIL IFX-derived signature peptides was inversely and strongly correlated with NAb concentration in the sample: R2 = 0.999. Evaluation data showed that the assay has a high specificity (100%) and a high sensitivity (94%) to predict NAb presence. Cross-validation against total ADA measured by a reference laboratory using radio immunoassay assay (RIA) for ADA provided a good correlation (r2 = 0.79). We developed for the first time a robust and fast screening method on the basis of LC-MS/MS to determine the presence of NAb and its neutralizing capacity in plasma. The analyses of NAb can be combined with therapeutic mAb quantification. Furthermore, the quantification of the neutralizing capacity expressed as mAb mass equivalents opens the door to new personalized dosing strategies in patients with NAb.


Prospective, randomized, controlled clinical trial of a novel matrix hemostatic sealant in children undergoing adenoidectomy.
Floseal is a novel matrix hemostatic sealant composed of collagen-derived particles and topical bovine-derived thrombin. It is applied as a high-viscosity gel for hemostasis and has been clinically proven to control bleeding. This study is a prospective, randomized, controlled clinical trial of Floseal sealant compared to traditional suction cautery hemostasis in children undergoing adenoidectomy. Seventy patients (mean age 7.0 yrs, 45.7% male) with obstructive sleep apnea underwent traditional cold steel adenoidectomy with an adenoid curette and were then randomized to receive the hemostatic sealant (Floseal) or cautery to obtain hemostasis. Patients were crossed over to the other hemostatic technique if hemostasis was not achieved after more than 100 mL of blood loss or 15 minutes elapsed time. Objective data collected included time to hemostasis and blood loss during hemostasis. Visual analog scales (VAS) were used to record subjective data by the operating surgeon including bleeding following adenoid pack removal (0 = none, 3 = brisk) and ease of operation (1 = extremely easy, 6 = extremely difficult). Parents recorded diet on a journal and were contacted by phone at postoperative day 7 and questioned with regard to return to regular diet and use of narcotics. Compared to patients in the cautery group (n = 35), Floseal patients (n = 35) had significantly shorter times to hemostasis (0.6 +/- 1.3 minutes vs 9.5 +/- 5.4 minutes [mean +/- SD], P < 0.001), less blood loss (2.5 +/- 9.2 mL vs 29.4 +/- 27.1 mL, P < 0.001), less subjective bleeding (0.0 +/- 0.6 vs 2.0 +/- 0.7, [median 4-point VAS +/- SD], P < 0.001), and subjectively easier operations (2.6 +/- 1.0 vs 5.2 +/- 1.0 [mean 6-point VAS +/- SD], P < 0.001). Furthermore, Floseal patients returned to regular diet earlier (2.7 +/- 0.7 vs 4.1 +/- 0.5 days [mean +/- SD], P < 0.001) and had less use of narcotics at 7 days postoperatively (40% vs 69%, P < 0.05). Lastly, three patients in the cautery group were crossed over to the Floseal group, but no Floseal subjects were crossed over to the cautery group. The retail cost of Floseal is US 85 dollars. Operating room costs are estimated at US 12 dollars/minute. Reducing the operative length by 8.9 minutes on average produces a cost savings of US 106.80 dollars per operation. There were no complications in either experimental group including postoperative hemorrhage, hospitalization, blood transfusion, or aspiration. Floseal matrix hemostatic sealant is a safe, efficacious, easy, and cost-effective technique for obtaining hemostasis in children undergoing adenoidectomy. Limitations of the study include the fact that it is nonblinded, which does allow for some bias in the subjective data recorded. However, utilizing 4 different operating surgeons, 3 of whom were not affiliated with the study, minimized this. CLINICAL SIGNIFICANCE OF STUDY: This study demonstrates the safety and efficacy of a novel hemostatic sealant in children undergoing adenoidectomy. Floseal matrix hemostatic sealant can be used as a first-line hemostatic agent, and it is a good tool in the armamentarium of otolaryngologists who encounter significant bleeding following adenoidectomy.


Hymenolepis diminuta: nuclear magnetic resonance analysis of the excretory products resulting from the metabolism of D-[13C6]glucose.
Excretory products of the tapeworm Hymenolepis diminuta, fed D-[13C6]glucose in vitro for 90 min, were studied using 1H and 13C nuclear magnetic resonance spectroscopy. Signals due to lactate, succinate, acetate, and alanine were identified in the spectra. Several differently labeled species were present for these metabolites; the variations of higher concentration were a consequence of metabolic factors while those of lower concentration could be accounted for by residual 12C in the glucose. The two major labeled lactates, U-13C and 2,3-13C2, were in the ratio 2:1, respectively, and the three major labeled succinates, 1,2,2'-13C3,2,2'-13C2, and U-13C, were present in the ratio 20:10:3, respectively. The different species of labeled end products are related to the overall glucose metabolism of H. diminuta.


Computer model of human lung morphology to complement SPECT analyses.
Aerosol therapy protocols could be improved if inhaled pharmacologic drugs were selectively deposited within the human lung. The targeted delivery to specific sites, such as receptors and sensitive airway cells, would enhance the efficacies of airborne pharmaceuticals. The high spatial discrimination of deposition patterns of inhaled particles can be determined via Single Photon Emission Computer Tomography (SPECT). However, major problems continue to compromise SPECT protocols. Our work focuses on two issues: how can the spatial discrimination be improved; and how are the images to be interpreted? We present a methodology, described by a mathematical model and supercomputer code, for systematically slicing through the human lung in a prescribed manner that is conducive to implementation into SPECT analyses. The lung is divided into concentric shells, or annuli, and the airway generation-by-generation composition of the respective shells determined. This identification was accomplished by superimposing the new shell structure with the 3-D branching network presented by Martonen et al. [23]. Perhaps the key aspect of the model-code is that the supercomputer is instructed to determine the 3-D spatial coordinates of each of the airways (over 16 million) of the lung with respect to the clinician-selected contours of shells within the lung.


Surgical resection of lung cancer in the elderly.
Assessment for thoracic surgery in elderly patients should be based on physiologic rather than chronologic age. Thoracic surgery has been shown to be safe in selected elderly patients, and age should not be a contraindication to a therapy that offers the best chance of cure for patients with early-stage cancer. A targeted preoperative assessment can help individualize the risk of morbidity and mortality for each patient, and thus provide both surgeon and patient with the information needed for operative decision making. Operative interventions in the elderly require coordinated attention to the specific requirements of the aged. Specialized multidisciplinary care provided by primary care physicians, geriatric specialists, cardiologists, oncologists, surgeons, anesthetists, nurses, physical therapists, and nutrition specialists optimizes care for the elderly patient undergoing thoracic surgery. Careful selection of patients for surgery has contributed to the improvement in operative mortality over time, and refinements in preoperative testing should continue this trend in the future. The goal is to provide surgery to the maximum number of patients at the minimal cost of mortality and loss of independence.


Versatility of percutaneous needle fasciotomy for Dupuytren's disease across a spectrum of disease severity: A single-surgeon experience of 118 rays.
Percutaneous needle fasciotomy (PNF) represents the only minimally invasive approach for treatment of Dupuytren's disease in Europe since withdrawal of collagenase from European markets. Though well-established, surgeon preference and uncertainty regarding safety and efficacy, results in limited provision in favour of open fasciectomy. A retrospective review of 74 patients who self-opted to receive PNF between 2017 and 2020 was conducted. Demographic data, complications and degree of release achieved were compared across three cohorts based on contracture severity as per Tubiana staging (TS): Stage 1, 0-45°; Stage 2, 46-90°; Stage 3, 91-130° with χ2 analysis. One hundred and eighteen rays were treated amongst 74 patients (mean age, 68 years (R, 32-86), males: 74%) with mean follow-up 51 weeks (IQR 28-76 weeks) with no significant difference in baseline characteristics across cohorts. No cases of permanent sensory disturbance, flexor tendon rupture, arterial transection nor infection were observed. Neuropraxia was seen in six patients, resolving with mean recovery of 6 weeks. 86% (n = 166) of joints had satisfactory release (residual passive extension deficit (PED) ≤10°) with full release in 67%. Full release was most likely in metacarpophalangeal joint (MCPJ; 93%) than distal interphalangeal joint (DIPJ; 67%) or proximal interphalangeal joint (PIPJ; 45%; p<0.0001). Mean release was 54° in MCPJ and 56° in PIPJ. All TS1 patients achieved release with ≤10° residual PED versus 75% of TS2 patients and 22% of TS3 patients (p<0.05), the latter of whom had a mean residual PED of 12° Ninety-two percent of patients stated they would undergo PNF again if necessary, in preference to open fasciectomy. We find PNF to facilitate a safe, effective yet minimally invasive approach amongst patients of varying disease severity, across different age groups, with recurrent disease, associated comorbidities or concurrent anticoagulation therapy. Patients reported high satisfaction in preference to open procedures. We, therefore, intend to recommend PNF first-line to all patients regardless of disease severity.


Molecular and Cellular Interactions of Allogenic and Autologus Mesenchymal Stem Cells with Innate and Acquired Immunity and Their Role in Regenerative Medicine.
Mesenchymal stem cells (MSCs), as major stem cells for cell therapy, have been studied from different aspects in preclinical and clinical settings for more than a decade. These cells modulate the immune system (humoral and cellular immune responses) in vitro by producing soluble factors (anti-inflammatory molecules) and/or making cell-cell contacts. Hence, they could be used in regenerative medicine, tissue engineering and immune therapy. MSCs-based therapy have been recently used for treatment of cancer regarding the migratory potential of these cells towards tumor cells which makes them considerable candidates, also for cell therapy in both allogeneic and autologous settings. So, this review attempts to focus on the factors secreted by MSCs such as cytokines, their functional role in mounting and controlling immune responses mediated by different immune cell subpopulations and their significance in regenerative medicine in clinical trials. Although, further studies remain to be done to increase our knowledge of regulating development mechanisms, homeostasis and tissue repair in order to provide new tools to implement the efficacy of cell therapy trials. Although MSCs have been proved safe and effective for cell therapy, there are still challenges to overcome before widely applying MSCs in clinic.


Influence of immunosuppressive treatment of Borna Disease in rabbits.
A total of 72 Borna Disease virus infected rabbits were treated with different concentrations of cyclophosphamide, glucocorticoids or both in combination. Comparison with untreated, infected rabbits showed a drastic alteration in the clinical picture, a considerable prolongation of the survival time, and differences in weight and body temperature during the course of the disease. The immunosuppressed animals had no or low amounts of antibodies in the serum and cerebrospinal fluid, but they harbored infectious virus and high amounts of specific antigen in the brain. A quotient of the relative amount of antibodies and antigen never exceeded 0.20 and was significantly lower than in untreated rabbits. Immunohistologically, differences in location and distribution of antigen as compared to positive untreated animals could not be detected. In the immunosuppressed animals perivascular infiltrates were not observed in the different regions of the brain.


Fat-fluid level in pleural effusion as a complication of a mediastinal dermoid: CT characteristics.
The CT findings in a 24-year-old woman with acute chest symptoms revealed excess mediastinal soft tissue and a fat-containing cavity. A fat-fluid level in a pleural effusion suggested preoperatively the diagnosis of mediastinal teratoma, which had leaked into the pleural space.


Molecular Beside Ionic: Crystal Structures of a 1/1 and a 1/4 Adduct of Pyridine and Formic Acid.
Of two low-melting binary adducts obtained with the same universal organic acid and base components, one contains these as the neutral molecules, the other, however, in a deprotonated and a protonated form as ions. Reports on analogous results for further Brønsted acid/base systems are rare. The complex anion, new in a crystal structure, is assembled by strong hydrogen bonds O-H⋅⋅⋅O (see formula).


Connectomes across development reveal principles of brain maturation.
An animal's nervous system changes as its body grows from birth to adulthood and its behaviours mature1-8. The form and extent of circuit remodelling across the connectome is unknown3,9-15. Here we used serial-section electron microscopy to reconstruct the full brain of eight isogenic Caenorhabditis elegans individuals across postnatal stages to investigate how it changes with age. The overall geometry of the brain is preserved from birth to adulthood, but substantial changes in chemical synaptic connectivity emerge on this consistent scaffold. Comparing connectomes between individuals reveals substantial differences in connectivity that make each brain partly unique. Comparing connectomes across maturation reveals consistent wiring changes between different neurons. These changes alter the strength of existing connections and create new connections. Collective changes in the network alter information processing. During development, the central decision-making circuitry is maintained, whereas sensory and motor pathways substantially remodel. With age, the brain becomes progressively more feedforward and discernibly modular. Thus developmental connectomics reveals principles that underlie brain maturation.


Stabilizing superconductivity in nanowires by coupling to dissipative environments.
We present a theory for a finite-length superconducting nanowire coupled to an environment. We show that in the absence of dissipation quantum phase slips always destroy superconductivity, even at zero temperature. Dissipation stabilizes the superconducting phase. We apply this theory to explain the "antiproximity effect" recently seen by Tian et al. in zinc nanowires.


Integrating molecular QTL data into genome-wide genetic association analysis: Probabilistic assessment of enrichment and colocalization.
We propose a novel statistical framework for integrating the result from molecular quantitative trait loci (QTL) mapping into genome-wide genetic association analysis of complex traits, with the primary objectives of quantitatively assessing the enrichment of the molecular QTLs in complex trait-associated genetic variants and the colocalizations of the two types of association signals. We introduce a natural Bayesian hierarchical model that treats the latent association status of molecular QTLs as SNP-level annotations for candidate SNPs of complex traits. We detail a computational procedure to seamlessly perform enrichment, fine-mapping and colocalization analyses, which is a distinct feature compared to the existing colocalization analysis procedures in the literature. The proposed approach is computationally efficient and requires only summary-level statistics. We evaluate and demonstrate the proposed computational approach through extensive simulation studies and analyses of blood lipid data and the whole blood eQTL data from the GTEx project. In addition, a useful utility from our proposed method enables the computation of expected colocalization signals using simple characteristics of the association data. Using this utility, we further illustrate the importance of enrichment analysis on the ability to discover colocalized signals and the potential limitations of currently available molecular QTL data. The software pipeline that implements the proposed computation procedures, enloc, is freely available at https://github.com/xqwen/integrative.


Expression of macromolecular organic nitrogen degrading enzymes identifies potential mediators of soil organic N availability to an annual grass.
Nitrogen (N) is frequently limiting to plant growth, in part because most soil N is present as polymeric organic compounds that are not readily taken up by plants. Microbial depolymerization of these large macromolecular N-substrates gradually releases available inorganic N. While many studies have researched and modeled controls on soil organic matter formation and bulk N mineralization, the ecological-spatial, temporal and phylogenetic-patterns underlying organic N degradation remain unclear. We analyzed 48 time-resolved metatranscriptomes and quantified N-depolymerization gene expression to resolve differential expression by soil habitat and time in specific taxonomic groups and gene-based guilds. We observed much higher expression of extracellular serine-type proteases than other extracellular N-degrading enzymes, with protease expression of predatory bacteria declining with time and other taxonomic patterns driven by the presence (Gammaproteobacteria) or absence (Thermoproteota) of live roots and root detritus (Deltaproteobacteria and Fungi). The primary chitinase chit1 gene was more highly expressed by eukaryotes near root detritus, suggesting predation of fungi. In some lineages, increased gene expression over time suggests increased competitiveness with rhizosphere age (Chloroflexi). Phylotypes from some genera had protease expression patterns that could benefit plant N nutrition, for example, we identified a Janthinobacterium phylotype and two Burkholderiales that depolymerize organic N near young roots and a Rhizobacter with elevated protease levels near mature roots. These taxon-resolved gene expression results provide an ecological read-out of microbial interactions and controls on N dynamics in specific soil microhabitats and could be used to target potential plant N bioaugmentation strategies.


[Effect of pharmacological substances on the altered permeability of the hemato-encephalic barrier for 14C-tyrosine due to ethanol].
It has been demonstrated that membrane-stabilizing agents, chlorpromazine and alpha-tocopherol, have no effect on the increased blood-brain barrier permeability for 14C-tyrosine, induced by a single injection of ethanol at a dose of 2 and 4 g/kg. Dopaminergic antagonist haloperidol prevented the increase of blood-brain barrier permeability induced by a single injection of 2 g/kg of ethanol and diminished the elevated barrier permeability caused by chronic 10-day alcoholization of animals, including abstinent ones. The role of membrane and neuromediator components in the mechanisms regulating blood-brain barrier functions is discussed.


[Anti-aggregation action of hypochlorite on the thrombocytes].
Sodium hypochlorite at concentrations higher than 1 mM suppresses ADP-dependent aggregation of blood platelets. The effect was associated with the process of cell modification. Blood platelet aggregation may be depressed partially by ADP destruction. Products of ADP-sodium hypochlorite interaction may lead to the induction of blood platelet aggregation, which is not so intensive than the ADP-induced one.


Timp1 Deletion Induces Anxiety-like Behavior in Mice.
The hippocampus is essential for learning and memory, but it also plays an important role in regulating emotional behavior, as hippocampal excitability and plasticity affect anxiety and fear. Brain synaptic plasticity may be regulated by tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a known protein inhibitor of extracellular matrix (ECM), and the expression of TIMP1 in the hippocampus can be induced by neuronal excitation and various stimuli. However, the involvement of Timp1 in fear learning, anxiety, and hippocampal synaptic function remains to be established. Our study of Timp1 function in vivo revealed that Timp1 knockout mice exhibit anxiety-like behavior but normal fear learning. Electrophysiological results suggested that Timp1 knockout mice showed hyperactivity in the ventral CA1 region, but the basic synaptic transmission and plasticity were normal in the Schaffer collateral pathway. Taken together, our results suggest that deletion of Timp1 in vivo leads to the occurrence of anxiety behaviors, but that Timp1 is not crucial for fear learning.


Alterations in the 'local umbilical cord blood renin-angiotensin system' during pre-eclampsia.
Local autocrine-paracrine renin-angiotensin system (RAS), independently functioning from the circulating RAS, is present in major organs of the female reproductive tract. We have previously demonstrated 'a local RAS in human umbilical cord' via verifying the corresponding ACE, renin, and angiotensinogen mRNAs. The aim of this study is to search alterations of the local umbilical cord RAS during pre-eclampsia. Cord blood samples were obtained from 19 patients with pre-eclampsia (aged mean 26.6 ± 5.83 (range 18-42) years) and 20 women with normal pregnancy (aged mean 28.26 ± 7.30 (range 19-37) years). Women with uncomplicated pregnancy formed the control group. Real time quantitative PCR analysis for ACE, renin and angiotensinogen gene expressions were carried out using a LightCycler™ instrument. The mean expression ratios were 0.0029 ± 0.0015 for renin, 0.153 ± 0.166 for angiotensinogen, and 0.220 ± 0.294 for ACE, in control samples. The mean expression ratios of pre-eclamptic patients were 0.0061 ± 0.00068, 0.035 ± 0.008, and 0.030 ± 0.006 for renin, angiotensinogen and ACE genes, respectively. While renin expressions increased in the local cord blood of pre-eclampsia in comparison to the normal cord blood, unpredictable decrements in the angiotensinogen and ACE expressions were observed within the same pre-eclamptic samples. There were no statistically significant differences between intrauterine growth restriction (IUGR) and appropriate for gestational age (AGA) newborns in respect to renin, angiotensinogen and ACE gene expressions. These findings indicate that the gene expression in the major components of the local RAS does not represent a constant mathematical model, but is affected from the ongoing pathobiological events associated with the disease course. Local umbilical cord blood RAS alterations at the basis of genetic expression are evident in pre-eclampsia.


Use of Desmopressin in Hyponatremia: Foe and Friend.
Use of desmopressin (1-deamino-8-d-arginine vasopressin; DDAVP), a synthetic vasopressin receptor agonist, has expanded in recent years. Desmopressin leads to renal water retention, and iatrogenic hyponatremia may result if fluid intake is not appropriately restricted. It is common practice to stop a medication that is causing toxicity, and this advice is promulgated in Micromedex, which suggests withholding desmopressin if hyponatremia occurs. If intravenous saline solution is administered and desmopressin is withheld at the same time, rapid changes in serum sodium levels may result, which puts the patient at risk for demyelinating lesions. In the management of desmopressin-associated hyponatremia with neurologic symptoms, the drug should not be withheld despite the presence of hyponatremia. The medication should be continued while administering intravenous hypertonic saline solution. Desmopressin is also used to minimize water excretion during the correction of hyponatremia during water diuresis. When treating hyponatremia, clinicians should monitor closely to avoid free-water diuresis. To prevent ongoing water losses in urine and overly rapid "autocorrection" of serum sodium level, desmopressin can be given to reduce free-water losses. These treatment recommendations are the authors' perspective from previously published work and personal clinical experience.


Visualizing Health Equity: Qualitative Perspectives on the Value and Limits of Equity Images.
Health educators and advocacy groups often use side-by-side visual images to communicate about equity and to distinguish it from equality. Despite the near-ubiquity of these images, little is known about how they are understood by different audiences. To assess the effectiveness of an image commonly used to communicate about health equity. In 167 interviews with health stakeholders in Greater Cleveland, Ohio, in 2018 to 2019, a commonly used health equity image was shown to participants, who were asked to interpret its meaning. Interviewees included 21 health professionals, 21 clinicians, 22 metro-wide decision makers, 24 community leaders, and 79 community members. About two thirds of our socioeconomically, racial/ethnically, educationally, and professionally diverse sample said the equity image helped clarify the distinction between "equality" and "equity." Yet less than one third offered an interpretation consistent with the image's goals of foregrounding not only injustice but also a need for systemic change. Patterns of misinterpretation were especially common among two groups: ideological conservatives and those of lower socioeconomic status. Conservatives were most likely to object to the image's message. Equity images are widely used by public health educators and advocates, yet they do not consistently communicate the message that achieving equity requires systemic change. In this moment of both public health crisis and urgent concern about systemic racism, new visual tools for communicating this crucial message are needed.


[The research of saffold virus in children with lower respiratory tract infection in Changsha].
To investigate prevalence of Saffold virus (SAFV) in Changsha area of hospitalized children with respiratory tract infection, and to discuss whether this virus is related to respiratory tract infection of children. 643 nasopharyngeal aspirates samples were collected from hospitalized children with respiratory tract infection of the first affiliated hospital of Hunan nomal university during Nov. 2007 to Oct. 2008. Real-time fluorescent quanti-tative PCR(FQ-PCR) performed to screen the 5'UTR gene. And then analyze clinical data. SAFV were detected in 67 patients (10.42%) out of the 643 children, it was not detected over 5 years of age. The virus were detected in 8 patients (25.81%) out of the 31 children with persistent pneumonia and chronic pneumonia, there was statistically significant. There existed SAFV infection in hospitalized children with lower respiratory infection in Changsha area; SAFV maybe related to disease onset with lower respiratory tract infection of children.


Sphingosylphosphorylcholine and lysosulfatide have inverse regulatory functions in monocytic cell differentiation into macrophages.
Sphingolipids act as signaling mediators that regulate a diverse range of cellular events. Although numerous sphingolipid functions have been studied, little is known about the effect of sphingolipids on monocyte differentiation into macrophages. Here, we report that two lysosphingolipids, sphingosylphosphorylcholine (SPC) and lysosulfatide (LSF), inversely affect macrophagic differentiation of monocytic cell lines, U937 and THP-1. Molecular analyses revealed that SPC enhances, whereas LSF suppresses, phorbol ester-induced classical (M1-polarized) differentiation to macrophages. The expression of CD11b, a macrophage marker, was induced in accordance with the activation status of the Raf/MEK/ERK signaling pathway in which SPC and LSF had opposite effects. Pharmacological inhibition of this pathway aborted the differentiation, indicating that this signaling pathway is required. Consistently, SPC promoted, while LSF inhibited, monocyte adhesion to fibronectin, through the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The effects of SPC on Raf/MEK/ERK and PI3K/Akt signaling were dependent on G(i/o), whereas the SPC-induced calcium influx was dependent on G(q). Thus SPC utilizes G-protein coupled receptor. In contrast, the effects of LSF were independent of G(i/o) and G(q). These results suggest that SPC enhances, whereas LSF suppresses, monocyte differentiation into macrophages through regulating the Raf/MEK/ERK and PI3K/Akt signaling pathways via distinct mechanisms.


Generation of two human control iPS cell lines (UCLi016-A and UCLi017-A) from healthy donors with no known ocular conditions.
Two human induced pluripotent stem cell (hiPSC) lines (UCLi016-A and UCLi017-A) were generated from fibroblast cells of 23- and 34-year-old healthy male donors with no known ocular conditions. Fibroblast cells were derived from skin biopsies and reprogrammed using integration free episomal reprogramming. The established iPSC lines were found to express pluripotency markers, exhibit differentiation potential in vitro and display a normal karyotype. These cell lines will act as a control lines for researchers studying ocular diseases.


Prunus lusitanica L. Fruits as a Novel Source of Bioactive Compounds with Antioxidant Potential: Exploring the Unknown.
Prunus lusitanica L., also known as Portuguese laurel or locally known as 'azereiro', is a rare species with ornamental and ecological value. Only two studies regarding the bioactivity and chemical composition of its leaves were reported to date. Thus, the present study aims to qualitatively and quantitatively evaluate the phenolic profile, through HPLC-PAD-ESI-MS/MS (high-performance liquid chromatography-photodiode array detection-electrospray ionization tandem mass spectrometry), as well as the radical scavenging capacity, through ABTS (2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid) and DPPH (2,2-diphenyl-1 picrylhydrazyl), and the reducing power (FRAP, ferric reducing antioxidant power) assays, of P. lusitanica fruits during a 4-year study. In total, 28 compounds were identified and quantified in the fruits, including 21 hydroxycinnamic acids (60.3%); 2 flavan-3-ols (27.9%), 2 anthocyanins (10.5%), 2 flavonols (1.0%), and 1 secoiridoid (0.3%). High antioxidant capacity was observed, with ABTS values ranging from 7.88 to 10.69 mmol TE (Trolox equivalents)/100 g fw (fresh weight), DPPH values from 5.18 to 8.17 mmol TE/100 g fw, and FRAP values from 8.76 to 11.76 mmol TE/100 g fw. According to these results, it can be concluded that these are rich sources of phenolic compounds with very promising antioxidant capacity and, therefore, with potential applications in the food and/or phytopharmaceutical sectors.


The place of patient satisfaction in quality assessment of lung cancer thoracic surgery.
To compare the quality of non-small cell lung cancer (NSCLC) surgical care with patient satisfaction. Prospective study. Academic hospital departments of thoracic oncology and surgery. Patients presenting with recently diagnosed NSCLC and eligible for front-line thoracic surgery were eligible. Patient satisfaction was assessed using the Questionnaire of Satisfaction of Hospitalized Patients. Quality of surgical care was evaluated using an original score built accordingly to British Thoracic Society guidelines. Univariate analysis used parametric (Pearson correlation, t test) and nonparametric tests (Mann-Whitney U test) according to test conditions. Probability of survival was estimated using the Kaplan-Meier method. Seventy patients (mean age, 63.7 years) were included. Lobectomy was performed in 62 cases, and pneumonectomy was performed in 8 cases. In all, 28 patients had a postoperative complication. One-year survival rates for patients with stage I-II and stage IIIA NSCLC were 84% and 58%, respectively. Mean patient satisfaction was 78 +/- 13/100 and 69 +/- 13/100 for global staff and structure index, respectively (+/- SD). Mean score for quality of surgical care was 88.7/100 (range, 51 to 100). The absence of postoperative complication was significantly related to a high level of satisfaction regarding the structure (r = 0.30, p < 0.05). Other features of patient satisfaction did not show a significant correlation with the quality of the preoperative selection process or the surgical procedure itself (r < 0.20). Considering the lack of significant correlation, the present study does not support a shortcut between quality of care and patient satisfaction. Nonetheless, patient satisfaction should be integrated into rather than substituted for the quality of health-care assessment, which also needs further development.


Vimar/RAP1GDS1 promotes acceleration of brain aging after flies and mice reach middle age.
Brain aging may accelerate after rodents reach middle age. However, the endogenous mediator that promotes this acceleration is unknown. We predict that the mediator may be expressed after an organism reaches middle age and dysregulates mitochondrial function. In the neurons of wild-type Drosophila (flies), we observed that mitochondria were fragmented in aged flies, and this fragmentation was associated with mitochondrial calcium overload. In a previous study, we found that mitochondrial fragmentation induced by calcium overload was reversed by the loss of Vimar, which forms a complex with Miro. Interestingly, Vimar expression was increased after the flies reached middle age. Overexpression of Vimar in neurons resulted in premature aging and mitochondrial calcium overload. In contrast, downregulation of Vimar in flies older than middle age promoted healthy aging. As the mouse homolog of Vimar, RAP1GDS1 expression was found to be increased after mice reached middle age; RAP1GDS1-transgenic and RAP1GDS1-knockdown mice displayed similar responses to flies with overexpressed and reduced Vimar expression, respectively. This research provides genetic evidence of a conserved endogenous mediator that promotes accelerated brain aging.


Mapping the Regioisomeric Space and Visible Color Range of Purely Organic Dual Emitters with Ultralong Phosphorescence Components: From Violet to Red Towards Pure White Light.
We mapped the entire visible range of the electromagnetic spectrum and achieved white light emission (CIE: 0.31, 0.34) by combining the intrinsic ns-fluorescence with ultralong ms-phosphorescence from purely organic dual emitters. We realized small molecular materials showing high photoluminescence quantum yields (ΦL ) in the solid state at room temperature, achieved by active exploration of the regioisomeric substitution space. Chromophore stacking-supported stabilization of triplet excitons with assistance from enhanced intersystem crossing channels in the crystalline state played the primary role for the ultra-long phosphorescence. This strategy covers the entire visible spectrum, based on organic phosphorescent emitters with versatile regioisomeric substitution patterns, and provides a single molecular source of white light with long lifetime (up to 163.5 ms) for the phosphorescent component, and high overall photoluminescence quantum yields (up to ΦL =20 %).


Regulation of intestinal concentration of cholecystokinin by bile and/or pancreatic juice.
Pancreatic exocrine secretion in conscious rats is regulated by intraluminal bile and/or pancreatic juice. Exclusion of bile and/or pancreatic juice from the intestinal lumen caused cholecystokinin (CCK) release and stimulated pancreatic secretion. CCK in the plasma is mainly derived from endocrine cells in the proximal small intestinal mucosa. We examined the changes in CCK concentrations in the intestinal mucosa and compared them to those of plasma CCK concentrations and the changes of luminal trypsin activities after bile and/or pancreatic juice diversion in conscious rats. Rats with bile and pancreatic fistulae were used. Each treatment of bile, pancreatic juice, and bile-pancreatic juice diversion decreased luminal trypsin activity and increased plasma and intestinal CCK concentrations. The potency of the stimulatory effect on plasma and intestinal CCK concentrations was bile-pancreatic juice diversion > pancreatic juice diversion > or = bile diversion. Neither plasma CCK concentration nor intestinal CCK concentration was in inverse proportion to trypsin activity. The plasma CCK concentration did not parallel intestinal CCK concentration. Intravenous infusion of CCK-8 (300 pmol/kg/hr) did not increase CCK concentration in the intestinal mucosa. It was proposed that bile and/or pancreatic juice in the intestinal lumen regulated CCK concentrations not only in the plasma but also in the intestinal mucosa.


Hereditary distal renal tubular acidosis: Genotypic correlation, evolution to long term, and new therapeutic perspectives.
Distal renal tubular acidosis (DRTA) is a rare disease resulting from a failure in the normal urine acidification process at the distal tubule and collecting duct level. It is characterised by persistent hyperchloremic metabolic acidosis, with a normal anion gap in plasma, in the presence of high urinary pH and low urinary excretion of ammonium. To date, 5 genes whose mutations give rise to primary DRTA have been described. Alterations in the ATP6V1B1 and ATP6V0A4 genes are inherited recessively and are associated with forms of early onset and, in many cases, with neurosensorial deafness. Pathogenic variants in the SLC4A1 gene are habitually inherited dominantly and give rise to milder symptoms, with a later diagnosis and milder electrolytic alterations. Nonetheless, evolution to nephrocalcinosis and lithiasis, and the development of chronic kidney disease in the medium to long term has been described in a similar manner in all 3 groups. Lastly, recessive forms of DTRA associated to mutations in the FOXI1 and WDR72 genes have also been described. The clinical management of DTRA is based on bicarbonate or citrate salts, which do not succeed in correcting all cases of the metabolic alterations described and, thus, the consequences associated with them. Recently, a new treatment based on slow-release bicarbonate and citrate salts has received the designation of orphan drug in Europe for the treatment of DTRA.


Aqueous Humor Analysis Identifies Higher Branched Chain Amino Acid Metabolism as a Marker for Human Leukocyte Antigen-B27 Acute Anterior Uveitis and Disease Activity.
Human leukocyte antigen-B27 (HLA-B27)-positive acute anterior uveitis (AAU) has a higher recurrence rate and shows more anterior chamber cell infiltration compared with HLA-B27-negative patients, suggesting distinct etiologies of these clinically overlapping conditions. To advance our understanding of the biology of AAU, we characterized the metabolic profile of aqueous humor (AqH) of patients with HLA-B27-associated AAU (B27-AAU) and noninfectious idiopathic AAU (idiopathic AAU). Experimental laboratory study. AqH samples from 2 independent cohorts totaling 30 patients with B27-AAU, 16 patients with idiopathic AAU, and 20 patients with cataracts underwent 2 individual rounds of direct infusion mass spectrometry. Features predicted by direct infusion mass spectrometry that facilitated maximum separation between the disease groups in regression models were validated by liquid chromatography/tandem mass spectrometry-based quantification with appropriate standards. Partial least square-discriminant analysis revealed metabolite profiles that were able to separate patients with B27-AAU from those with iodiopathic AAU. Pathway enrichment analysis, based on metabolites on which separation of the groups in the partial least square-discriminant analysis model was based, demonstrated the involvement of branched-chain amino acid biosynthesis, ascorbate and aldarate metabolism, the tricarboxylic acid cycle, and glycolysis-diverting pathways (eg, serine biosynthesis) across all investigated cohorts. Notably, the metabolite ketoleucine was elevated in B27-AAU across all 3 runs and moderately-but robustly-correlated with anterior chamber cell count (correlation coefficient range 0.41-0.81). These results illustrate metabolic heterogeneity between HLA-B27-positive and HLA-B27-negative AAU, including an increase of branched-chain amino acid biosynthesis, that reflects disease activity in AAU.


Subjective wellbeing and temporal patterns of sympathetic-adrenal medullary activity.
Sixteen male subjects performed an audiovisual-conflict during 1 h of an ordinary day of work. Adrenaline and noradrenaline excretion and subjective reactions were measured before, during, and after the test period as well as at corresponding points in time in a control day of ordinary work with interruption. This program was carried out on two occasions, which were expected to differ with respect to the subjects' general mental condition and wellbeing. There were large intraindividual as well as interindividual variations in the rate at which adrenaline output decreased after the stress period. The results support the hypothesis that rapid recovery to baseline levels is positively related to a relaxed, alert and subjectively pleasant state of mind.


Prevalence and associated factors of pelvic organ prolapse among women attending gynecologic clinic in referral hospitals of Amhara Regional State, Ethiopia.
While pelvic organ prolapse is common in clinical observation, there is a lack of evidence regarding its actual proportion and associated factors in the study area. Understanding the prevalence and risk factors could potentially help with prevention. Thus, this study aimed to determine the prevalence and associated factors related to pelvic organ prolapse in the Amhara region, northwest Ethiopia. An institutional-based cross-sectional study was conducted among 424 women, recruited by the systematic random sampling technique. Data were collected in a face-to-face interview using a structured and pre-tested questionnaire to assess the symptoms of pelvic organ prolapse and the socio-demographic, obstetric, gynecologic, medical and surgical characteristics. The stage of prolapse was determined by pelvic examination using the Simplified Pelvic Organ Prolapse Quantification staging system. Descriptive statistics and logistic regression analyses were employed. The overall prevalence of pelvic organ prolapse (stage I-IV) was found to be 37.6% when determined by pelvic examination and 9.2% as assessed by prolapse symptoms. Age ≥ 40 years [AOR 2.46 (1.320, 5.314)], age at first delivery ≤ 20 years [AOR 4.719 (2.44, 9.11)], carrying heavy objects for ≥ 5 hours a day [AOR 12.724 (4.89, 33.07)], parity ≥ 4 [AOR 3.739 (1.693, 8.208)], prolonged labor [AOR 3.487 (1.699, 7.159)], constipation [AOR 2.835 (1.273, 6.317)] and anemia [AOR 2.22 (1.049, 4.694)] were significantly associated with pelvic organ prolapse. Prevalence of pelvic organ prolapse is high in the area; thus, developing information and education programs on avoiding risk factors is advisable to reduce the problem.


Interferon inducer, polyriboguanylic.polyribocytidylic acid, inhibits experimental hepatic metastases in mice.
The antitumour activity of an interferon inducer, the double-stranded complex of polyriboguanylic.polyribocytidylic acid was studied on murine lymphosarcoma LS/BL. The antitumour effect was determined with the aid of an experimental liver-colony model and compared to that exhibited by another synthetic RNA, polyriboinosinic.polyribocytidylic acid. We found that both polynucleotide complexes decreased the number of liver colonies and prolonged the survival of the tumour-bearing mice. This effect was only observed if the complexes were applied in an appropriate dose schedule which included the administration of the drug prior to tumour cell inoculation and subsequent continuous treatment. We have also verified that the polynucleotide complexes did not exert their antitumour effect by a direct action on tumour cells.


Relationships Between Köhne Category/Baseline Tumor Load and Early Tumor Shrinkage, Depth of Response, and Outcomes in Metastatic Colorectal Cancer.
In metastatic colorectal cancer (mCRC), there are limited data on associations between early tumor shrinkage (ETS), depth of response (DpR), and patient characteristics. Data from patients with RAS wild-type mCRC who had participated in the PRIME (NCT00364013) and PEAK (NCT00819780) studies were analyzed retrospectively. ETS and DpR were assessed by baseline Köhne category/BRAF status (PRIME) and baseline tumor load (pooled PRIME and PEAK). Analysis populations included 436 to 665 patients. Patients' chances of achieving ETS of 30% or greater were 63.8%, 50.4%, and 41.9% in the low-, medium-, and high-risk Köhne categories, and 21.7% in those with BRAF mutations. Corresponding percentages for the highest DpR classification (71%-100%) were 47.7% (low risk), 23.6% (medium risk), 10.0% (high risk), and 4.2% (BRAF mutant). No clear relationship was observed between baseline tumor load and ETS or DpR. An ETS of 30% or greater and higher DpR values were associated with statistically significant prolongation of median progression-free survival and overall survival. Patients with mCRC categorized at baseline by the Köhne criteria as high risk or with BRAF mutations have lower chances of achieving an ETS of 30% or greater or a high DpR. Baseline tumor load was not predictive of ETS or DpR. Favorable ETS or DpR is associated with improved progression-free and overall survival.


Primary peritoneal neuroblastoma: computed tomography findings.
Primary peritoneal tumors are rare neoplasms. The computed tomography findings in an adult patient with a primary peritoneal neuroblastoma are described. Discussion of these uncommon neoplasms and this unusual presentation of neuroblastoma forms the basis of this report.


Might High-Intensity Interval Exercise Be Remembered as More Pleasurable? An Attempt to Test the Peak-End Rule in the Exercise Context.
Given humans' limited ability to recall past experiences for evaluation, scholars have proposed the peak-end rule stating that if perceived discomfort at the end of an aversive experience is lower than the peak discomfort experienced, the aversive experience will be remembered more positively. The purpose of this study was to evaluate the peak-end rule as applied to high-intensity interval exercise (HIIE). Participants were 30 inactive men (M age = 27.9, SD = 5.2 years). In the first session they performed a graded exercise test on cycle-ergometer to determine their maximal aerobic power (MAP) (M = 233, SD = 35W); and, in the second and third sessions, they performed two HIIE protocols in randomized order: (a) Short trial - 20-minutes of HIIE, composed of 30-second efforts at 100% of MAP interspersed by 30-seconds of passive recovery; and (b) Long trial - 20-minutes of the short trial, plus 10-minutes more of HIIE, decreasing 3% of MAP in each additional bout, resulting in 70% of MAP in the last bout. During exercise, we recorded the participants' rating of perceived exertion (RPE) and affect, using the Feeling Scale (FS). At 30-minutes post-exercise, we again recorded the participants' affect, using the Global Affect Evaluation (GAE) and their session-RPE, and we recorded their enjoyment, using the Physical Activity Enjoyment Scale (PACES). In the last session, the participants chose a favorite protocol to repeat. All sessions were interspersed by at least 72 hours. The 10-minutes extra HIIE in the Long-trial condition resulted decreased heart rate values (M = 157, SD = 13bpm to M = 144, SD = 14bpm; p < 0.001), but psychological responses during and after exercise did not differ, nor did participants' preferred HIIE protocol. As the load drop for the Long-trial was not enough to change the psychological responses during exercise, there was no difference in the retrospective evaluation as the peak-end rule would have suggested.


Validating TDP1 as an Inhibition Target for the Development of Chemosensitizers for Camptothecin-Based Chemotherapy Drugs.
Cancer chemotherapy sensitizers hold the key to maximizing the potential of standard anticancer treatments. We have a long-standing interest in developing and validating inhibitors of the DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (TDP1) as chemosensitizers for topoisomerase I poisons such as topotecan. Herein, by using thieno[2,3-b]pyridines, a class of TDP1 inhibitors, we showed that the inhibition of TDP1 can restore sensitivity to topotecan, results that are supported by TDP1 knockout cell experiments using CRISPR/Cas9. However, we also found that the restored sensitivity towards topoisomerase I inhibitors is likely regulated by multiple complementary DNA repair pathways. Our results showed that one of these pathways is likely modulated by PARP1, although it is also possible that other redundant and partially overlapping pathways may be involved in the DNA repair process. Our work thus raises the prospect of targeting multiple DNA repair pathways to increase the sensitivity to topoisomerase I inhibitors.


Amyloid-Tau-Neurodegeneration Profiles and Longitudinal Cognition in Sporadic Young-Onset Dementia.
We examined amyloid-tau-neurodegeneration biomarker effects on cognition in a Southeast-Asian cohort of 84 sporadic young-onset dementia (YOD; age-at-onset <65 years) patients. They were stratified into A+N+, A- N+, and A- N- profiles via cerebrospinal fluid amyloid-β1-42 (A), phosphorylated-tau (T), MRI medial temporal atrophy (neurodegeneration- N), and confluent white matter hyperintensities cerebrovascular disease (CVD). A, T, and CVD effects on longitudinal Mini-Mental State Examination (MMSE) were evaluated. A+N+ patients demonstrated steeper MMSE decline than A- N+ (β = 1.53; p = 0.036; CI 0.15:2.92) and A- N- (β = 4.68; p = 0.001; CI 1.98:7.38) over a mean follow-up of 1.24 years. Within A- N+, T- CVD+ patients showed greater MMSE decline compared to T+CVD- patients (β = - 2.37; p = 0.030; CI - 4.41:- 0.39). A+ results in significant cognitive decline, while CVD influences longitudinal cognition in the A- sub-group.


Effectiveness of a tooth-brushing programme using the picture exchange communication system (PECS) on gingival health of children with autism spectrum disorders.
The Picture Exchange Communication System (PECS) is a communication system for children with autism spectrum disorders (ASD). The aim of this study was to assess the effect of a PECS-based tooth-brushing programme on gingival health in children with ASD and assess parents' perception of PECS. This was a prospective interventional study. Using PECS as a pictures/cards series showing a structured tooth-brushing method, 37 children with ASD (31 males, 6 females) (average age 9.49 ± 4.10, 4-16 years) and their parents/caregivers were trained on tooth-brushing twice, 2 weeks apart. Data collected after examinations (baseline, 3, 6-months) included gingival and plaque indices (GI, PI) and two questionnaires (baseline, 6-months) for demographic data and parents' perception of PECS including difficulty rating (easy, hard, very hard) and PECS usefulness. Most children with ASD had language abilities (64.9%) and prior PECS use (67.6%). Both GI and PI significantly dropped between baseline and both re-evaluations, (P < 0.001). Age, among studied factors, significantly affected PI only at all stages (P < 0.001). Most parents/caregivers (75.7%) rated PECS as hard, but useful (100%). Age and PECS prior use significantly affected PECS difficulty rating (P = 0.000 and 0.031, respectively), while sex did not (P > 0.05). PECS though rated as hard was useful in improving gingival health in children with ASD.


Purification of mitochondria and secretory granules isolated from pancreatic beta cells using Percoll and Sephacryl S-1000 superfine.
Mitochondria and secretory granules were isolated from beta-cell-rich pancreatic islets of ob/ob mice. Crude fractions obtained by differential centrifugation were subjected to centrifugation on isotonic Percoll. The gradient medium was removed from the resulting fractions by gel filtration on Sephacryl S-1000 Superfine. When compared to the crude fractions, the purified mitochondrial fraction exhibited a 4.5-fold increase in citrate synthase activity, a 70% reduction of lysosomal arylsulfatase, and a 40% decrease of contamination with granular insulin. In the purified secretory granule fraction, the insulin content was as high as 60% of the total protein (albumin standard) with arylsulfatase unchanged and no detectable citrate synthase activity.


Malicious traffic detection combined deep neural network with hierarchical attention mechanism.
Given the gradual intensification of the current network security situation, malicious attack traffic is flooding the entire network environment, and the current malicious traffic detection model is insufficient in detection efficiency and detection performance. This paper proposes a data processing method that divides the flow data into data flow segments so that the model can improve the throughput per unit time to meet its detection efficiency. For this kind of data, a malicious traffic detection model with a hierarchical attention mechanism is also proposed and named HAGRU (Hierarchical Attention Gated Recurrent Unit). By fusing the feature information of the three hierarchies, the detection ability of the model is improved. An attention mechanism is introduced to focus on malicious flows in the data flow segment, which can reasonably utilize limited computing resources. Finally, compare the proposed model with the current state of the method on the datasets. The experimental results show that: the novel model performs well in different evaluation indicators (detection rate, false-positive rate, F-score), and it can improve the performance of category recognition with fewer samples when the data is unbalanced. At the same time, the training of the novel model on larger datasets will enhance the generalization ability and reduce the false alarm rate. The proposed model not only improves the performance of malicious traffic detection but also provides a new research method for improving the efficiency of model detection.


[Down's syndrome in the Basque autonomous community, 1990-1995: types of birth and follow-up of a cohort of 116 children during the first year of life. Registry of anomalies].
The aim of this study was to assess the frequency of associated anomalies in babies with Down's syndrome (DS) and their progress throughout the first year of life. All pregnancies of women resident in the Basque Autonomous Community with prenatal or postnatal diagnosis of DS ascertained during the period 1990-1995 were studied. A one year follow-up of all DS babies was carried out. One hundred and sixteen live born DS babies were identified. Half of them (58) showed other associated anomalies. Congenital heart disease (CHD) was the most frequent anomaly, present in 45 cases. Atrioventricular canal (AVC) was the most frequent type of CHD, present in 34 out of the 45, the complete from being more prevalent (2/3). A marked association between AVC and female sex was observed. The overall mortality in the first year of life was 18.1%, associated to the presence of CHD. These findings are in keeping with the observations reported in previous similar studies. Consistency of these population-based data over time provides and accurate and reliable basis both for planning the needs of children with DS and to counsel affected parents.


Pharmacological intervention in older patients with rheumatoid arthritis. Quality of life aspects.
Despite the rather pessimistic outlook regarding the long term effects of pharmacological treatment of patients with rheumatoid arthritis (RA), there is no doubt that drug interventions can affect quality of life (QOL). The disease has a significant impact upon physical, psychological and social function, and QOL optimisation should cover all these dimensions. Swelling of joints and pain are important manifestations in assessing RA since these may result in sleep disturbances as well as depressed mood. This might be particularly significant for older persons with RA. Outcome parameters of RA can be divided into short, intermediate and long term. The long term results are quite disappointing with regard to disability and premature death. However, more intermediate outcome measures related to QOL might improve after pharmacological interventions. Patient preferences and expectations with regard to the outcome of pharmacological interventions are important parameters to assess. When assessing older patients with RA with QOL instruments, it is recommended that questionnaires are fairly short and easy to complete. Adverse effects of pharmacological interventions are important factors to monitor in QOL assessment in older patients with reduced remaining life span.


Recurrent angiomatoid fibrous histiocytoma: a case report and review of the literature.
Angiomatoid fibrous histiocytoma (AFH) is a rare soft-tissue tumor with intermediate malignant potential. It most commonly occurs in children and young adults. We report a case of a recurrent AFH of the back, locally recurring within 14 months of the original operation. We also review the literature for this uncommon entity. The patient underwent a wide resection of the recurrent AFH, obtaining negative surgical margins. Postoperatively, he has done well. Twelve months since his re-excision, the patient shows no evidence of recurrence to date. He is seen every 6 months for continued clinical examinations.


Strengthening health information librarianship in Africa through associations and partnerships: personal reflections in memory of Shane Godbolt.
This paper describes the significant roles Shane Godbolt played in promoting partnerships and collaborations and strengthening the Association for Health Information and Libraries in Africa (AHILA). It presents the personal reflections of each author about Shane, the part she played in their professional and personal lives as well as Shane's vital support for AHILA and AHILA members during her lifetime.


Quality of partogram monitoring at a primary health centre in Zambia.
The World Health Organization (WHO) recommends using a partogram to reduce maternal and neonatal mortality, especially in developing countries. Some previous studies conducted in African countries suggested that appropriate use of a partogram with standardised monitoring was associated with good labour outcomes. However, the compliance rates of recording differed among the monitoring items on the partogram and the quality of monitoring has not been examined adequately. to examine the compliance for each monitoring item on the WHO partogram and the quality of the monitoring. a retrospective and observation study. a retrospective review of partograms (n=200) was undertaken in a health centre in Lusaka, Zambia. We excluded referral cases, admission with full dilatation, birth before arrival, childbirth within 30 minutes, and false labour. Finally, 125 partograms were examined to assess the recording compliance for each monitoring item. An observation study in the delivery room and interviews with midwives were also conducted to examine the quality of monitoring for labour. The research ethics committee of the Division of Health Sciences, Osaka University Graduate School of Medicine and the Biomedical Research Ethics Committee of the University of Zambia approved the study. the lowest recording rate of the frequency of uterine contractions at the time of admission was 69.6%. The highest compliance rates in the active phase were found for the descent of the fetal head and cervix dilatation at 97.6% and 97.3%, respectively. The lowest rate was found for the mother's pulse rate at 25.5%, whereas 27.1% of the women admitted in the latent phase were diagnosed as entering the active phase in the acceleration phase. In addition, the methods of abdominal palpation for assessing uterine contractions and intermittent fetal heart rate monitoring were not appropriate. Zambian midwives have acquired sufficient understanding regarding the usefulness of the WHO partogram. However, there were differences in the compliance rates for each monitoring item due to a lack of medical devices and inappropriate monitoring skill. To improve labour outcomes with the WHO partogram, it is necessary to improve the recording and compliance rates for each monitoring item, as well as to upgrade the quality of monitoring.