A value-based practice model of rehabilitation: consumers' recommendations in action.
The purpose of this paper is to present a model of rehabilitation practice that is based on the recommendations of consumers who used rehabilitation services and have a life-changing physical impairment (spinal cord injury - SCI). This value-based practice model is based on two qualitative studies. The first study developed the framework (social adaptation) for a new practice model based on values. The second study, described in this paper, used the framework to learn about recommendations for change in the rehabilitation process. Participants in the second study were 80 volunteers who live with a SCI in the community, across the province of Ontario, Canada. A snowball strategy was used to recruit interested participants. Participants were involved in face-to-face interviews which included questions on what helped and hindered their initial rehabilitation process, and their recommendations for change. In this paper, we described a model that demonstrates how consumer input is essential in shaping a comprehensive rehabilitation process. The model is based on overarching value statements that express the worthiness of all individuals, the value of the lived experience of disability and the responsibility of the rehabilitation process to enable client autonomy. Four "values in action" are articulated: caring and respect for the individual and his/her personhood; applying the lived experience of disability; fostering autonomy; and promoting hopefulness. These values have been initially described in another paper based on a specific subset of 15 women living with SCI related to body issues during rehabilitation. This paper builds on this value work and we develop key practices for a progressive rehabilitation culture and model, based on the larger study group of 80 participants (men and women with SCI). This value-based model, when integrated with traditional, physical improvement-focused rehabilitation, has the potential to create a more effective process by offering clients better support as they go through the complex process of re-building their lives and making the transition back to the community. Implications for Rehabilitation We suggest that the Values in the Action Rehabilitation Practice Model that emphasized social adaptation be used along side the physical rehabilitation approach to enhance client-based practice. That peers with disabilities work collaboratively with rehabilitation professionals within a culture that acknowledges and reimburses their knowledge and expertise. Rehabilitation professionals learn about the lived experience of disability and systemic issues by being involved in grass-roots community organizations.


Impact of the acuity circle model for liver allocation on multivisceral transplant candidates.
Liver allocation was updated on February 4, 2020, replacing a Donor Service Area (DSA) with acuity circles (AC). The impact on waitlist outcomes for patients listed for combined liver-intestine transplantation (multivisceral transplantation [MVT]) remains unknown. The Organ Procurement and Transplantation Network/United Network for Organ Sharing database was used to identify all candidates listed for both liver and intestine between January 1, 2018 and March 5, 2021. Two eras were defined: pre-AC (2018-2020) and post-AC (2020-2021). Outcomes included 90-day waitlist mortality and transplant probability. A total of 127 adult and 104 pediatric MVT listings were identified. In adults, the 90-day waitlist mortality was not statistically significantly different, but transplant probability was lower post-AC. After risk-adjustment, post-AC was associated with a higher albeit not statistically significantly different mortality hazard (sub-distribution hazard ratio[sHR]: 8.45, 95% CI: 0.96-74.05; p = .054), but a significantly lower transplant probability (sHR: 0.33, 95% CI: 0.15-0.75; p = .008). For pediatric patients, waitlist mortality and transplant probability were similar between eras. The proportion of patients who underwent transplant with exception points was lower post-AC both in adult (44% to 9%; p = .04) and pediatric recipients (65% to 15%; p = .002). A lower transplant probability observed in adults listed for MVT may ultimately result in increased waitlist mortality. Efforts should be taken to ensure equitable organ allocation in this vulnerable patient population.


Inhibition of polo-like kinase 1 (Plk1) enhances the antineoplastic activity of metformin in prostate cancer.
The widely used anti-diabetic drug metformin has been shown to exert strong antineoplastic actions in numerous tumor types, including prostate cancer (PCa). In this study, we show that BI2536, a specific Plk1 inhibitor, acted synergistically with metformin in inhibiting PCa cell proliferation. Furthermore, we also provide evidence that Plk1 inhibition makes PCa cells carrying WT p53 much more sensitive to low-dose metformin treatment. Mechanistically, we found that co-treatment with BI2536 and metformin induced p53-dependent apoptosis and further activated the p53/Redd-1 pathway. Moreover, we also show that BI2536 treatment inhibited metformin-induced glycolysis and glutamine anaplerosis, both of which are survival responses of cells against mitochondrial poisons. Finally, we confirmed the cell-based observations using both cultured cell-derived and patient-derived xenograft studies. Collectively, our findings support another promising therapeutic strategy by combining two well tolerated drugs against PCa proliferation and the progression of androgen-dependent PCa to the castration-resistant stage.


Setup for high-throughput impedance screening of gas-sensing materials.
This paper reports on the setup for a high-throughput impedance measurement system that allows rapid screening of the electrical and dielectrical properties of solid-state sample libraries in variable atmospheres and temperatures. Using multielectrode arrays, most time-consuming steps in the workflow are parallelized. In addition, an approach for automated data evaluation of impedance spectra is presented. For reasons of verification of robust measuring results and reproducibility, screening results of a sample library composed of doped indium(III) oxide as a resistive-type gas-sensing material are discussed on the basis of the determined sensitivities focusing temperature and testing gas gradients.


Hemodynamic and biologic determinates of arteriovenous fistula outcomes in renal failure patients.
The outcome of patients with end-stage renal disease on hemodialysis depends on a functioning vascular access. Although a variety of access options are available, the arteriovenous fistula remains the best vascular access. Unfortunately the success rate of mature fistula use remains poor. The creation of an arteriovenous fistula is followed by altered hemodynamic and biological changes that may result in neointimal hyperplasia and eventual venous stenosis. This review provides an overview of these changes and the needed research to provide a long lasting vascular access and hence improve outcomes for patients with end-stage renal disease.


Coronavirus (COVID-19) and sexualised drug use among men who have sex with men: a systematic review.
Drug-related harms, including harms from sexualised drug use (SDU), are disproportionately experienced by sexual and gender minority people, relative to their majority counterparts. Chemsex, a type of SDU practiced mainly by MSM, is associated with methamphetamine use and increased HIV seropositivity or risk of acquisition. Therefore, participants are at increased risk of immunocompromise. Existing evidence suggests that drug use increases following natural disasters. The impact of coronavirus disease 2019 (COVID-19) on chemsex is unknown. A PRISMA-adherent systematic review was conducted to synthesise reports of changes in the prevalence, frequency, or characteristics of drug use (and factors associated with these changes) following the onset of the COVID-19 pandemic. This report presents findings related to SDU/chemsex among MSM. A comprehensive search across nine databases, supplemented with backward-forward citation searching and contact with key opinion leaders, was conducted. Two reviewers carried out title-abstract screening, full-text screening, and data extraction. Following a final, single database search, nine studies were included in the narrative synthesis. More than half the sample were studies investigating HIV pre-exposure prophylaxis use. Twenty percent of participants in most studies reported chemsex participation. In four, participants reported a net increase or maintenance of chemsex participation during the pandemic and five reported a net decrease. Increased chemsex participation was associated with loneliness, cravings, and working during the pandemic. Decreased chemsex practice was associated with COVID-19-related fear. This synthesis suggests that chemsex practice continued, and for some MSM increased, throughout COVID-19 pandemic 'lockdowns'. This may have increased COVID-19 transmission and severity among potentially vulnerable MSM.


Correct integration of retroviral DNA in vitro.
We have developed a cell-free system for studying the integration of retroviral DNA. In our assay, amber mutations in a bacteriophage lambda genome that serves as the target for integration are suppressed by integration of an MLV derivative that carries the E. coli supF gene. The structure of the reaction products is that expected from an authentic MLV integration reaction. Linear viral DNA from the cytoplasm of infected cells serves as a precursor, though not necessarily the immediate precursor, to the provirus integrated in vitro. The viral DNA in the infected cell appears to be tightly associated with the enzymatic machinery required for its integration. Supercoiling, chromatin structure, transcription, and replication are not required of the target DNA. Since no high-energy cofactor is necessary, the DNA breakage and joining steps in the integration reaction are probably coupled.


Recent developments on production, purification and biological activity of marine peptides.
Marine peptides are one of the richest sources of structurally diverse bioactive compounds and a considerable attention has been drawn towards their production and bioactivity. However, there is a paucity in consolidation of emerging trends encompassing both production techniques and biological application. Herein, we intend to review the recent advancements on different production, purification and identification technologies used for marine peptides along with presenting their potential health benefits. Bibliometric analysis revealed a growing number of scientific publications on marine peptides (268 documents per year) with both Asia (37.2%) and Europe (33.1%) being the major contributors. Extraction and purification by ultrafiltration and enzymatic hydrolysis, followed by identification by chromatographic techniques coupled with an appropriate detector could yield a high content of peptides with improved bioactivity. Moreover, the multifunctional health benefits exerted by marine peptides including anti-microbial, antioxidant, anti-hypertension, anti-diabetes and anti-cancer along with their structure-activity relationship were presented. The future perspective on marine peptide research should focus on finding improved separation and purification technologies with enhanced selectivity and resolution for obtaining more novel peptides with high yield and low cost. In addition, by employing encapsulation strategies such as nanoemulsion and nanoliposome, oral bioavailability and bioactivity of peptides can be greatly enhanced. Also, the potential health benefits that are demonstrated by in vitro and in vivo models should be validated by conducting human clinical trials for a technology transfer from bench to bedside.


The mediational role of adolescents' friends in relations between activity breadth and adjustment.
This investigation addresses the mediational role of friends' characteristics between adolescents' activity breadth (i.e., variety in activity participation) and their later adjustment. Data were drawn from 2 longitudinal studies: the Childhood and Beyond (CAB; N = 925) study and the Maryland Adolescent Development in Context Study (MADICS; N = 1,338). Adolescents at Time 2 in each study (8th, 9th, and 11th graders in CAB and 8th graders in MADICS) reported on the breadth of their participation across 5 activity settings: sports, religious, volunteering, community, and school. Friends' characteristics and adolescent adjustment were reported by adolescents at Times 1 and 3. Friends' positive characteristics significantly mediated relations between activity breadth and adolescent depressive affect, self-worth, alcohol use, and problem behavior in both studies. Friends' negative characteristics significantly mediated these relations in CAB, but not in MADICS.


Dental plaque flora of the dog with reference to fastidious and anaerobic bacteria associated with bites.
Animal bite wounds are amongst the most common types of traumatic injuries in humans. The organisms isolated from these wounds generally reflect the oral flora of the biting animal, and may be fastidious in nature and difficult to identify. This study was undertaken to determine the prevalence of Eikenella corrodens, Actinobacillus actinomycetemcomitans, Porphyromonas and Prevotella spp. in supragingival dental plaque collected from the right maxillary canine and carnassial teeth and the right mandibular canine tooth of dogs. In part one of the study, 30 dogs were used. E. corrodens was found in 62% of these dogs and 44% of individual plaque samples. A. actinomycetemcomitans was not detected in any of the dogs sampled. In part two, 34 dogs were used to determine the prevalence of the black pigmented anaerobic bacilli (Porphyromonas and Prevotella spp.). Porphyromonas gingivalis was present in 68% of these dogs and 47% of individual plaque samples. Prevotella intermedia was present in 44% of the dogs and 23% of individual plaque samples. The recently described Porphyromonas canoris, Porphyromonas salivosa, Porphyromonas cangingivalis, Porphyromonas cansulci, Porphyromonas crevioricanis and Prevotella denticola species were isolated from only 9%, 6%, 3%, 3%, 3% and 3% of dogs respectively. Porphyromonas gingivicanis was not isolated from any of the animals sampled. In conclusion, black-pigmented anaerobic bacilli were isolated from 91% of the animals sampled and therefore constitute a significant risk with respect to bite wound infections. It is also suggested that the prevalence of E. corrodens in wound infections has been underestimated in previous reports because of use of inappropriate techniques for detecting this organism.


Inactivation of retroviruses with preservation of structural integrity by targeting the hydrophobic domain of the viral envelope.
We describe a new approach for the preparation of inactivated retroviruses for vaccine application. The lipid domain of the viral envelope was selectively targeted to inactivate proteins and lipids therein and block fusion of the virus with the target cell membrane. In this way, complete elimination of the infectivity of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) could be achieved with preservation of antigenic determinants on the surface of the viral envelope. Inactivation was accomplished by modification of proteins and lipids in the viral envelope using the hydrophobic photoinduced alkylating probe 1,5 iodonaphthylazide (INA). Treatment of HIV and SIV isolates with INA plus light completely blocked fusion of the viral envelope and abolished infectivity. The inactivated virus remained structurally unchanged, with no detectable loss of viral proteins. Modifications to envelope and nucleocapsid proteins were detected by changes in their elution pattern on reverse-phase high-performance liquid chromatography. These modifications had no effect on primary and secondary structure epitopes as determined by monoclonal antibodies. Likewise, the inactivated HIV reacted as well as the live virus with the conformation-sensitive and broadly neutralizing anti-HIV type 1 monoclonal antibodies 2G12, b12, and 4E10. Targeting the lipid domain of biological membranes with hydrophobic alkylating compounds could be used as a general approach for inactivation of enveloped viruses and other pathogenic microorganisms for vaccine application.


Whole exome sequencing identifies a heterozygous missense variant in the PRDM5 gene in a family with Axenfeld-Rieger syndrome.
Axenfeld-Rieger syndrome (ARS) is a disorder affecting the anterior segment of the eye, often leading to secondary glaucoma and several systemic malformations. It is inherited in an autosomal dominant fashion that has been associated with genetic defects in PITX2 and FOXC1. Known genes CYP1b1, PITX2, and FOXC1 were excluded by Sanger sequencing. The purpose of current study is to identify the underlying genetic causes in ARS family by whole exome sequencing (WES). WES was performed for affected proband of family, and variants were prioritized based on in silico analyses. Segregation analysis of candidate variants was performed in family members. A novel heterozygous PRDM5 missense variant (c.877A>G; p.Lys293Glu) was found to segregate with the disease in an autosomal dominant fashion. The novel missense variant was absent from population-matched controls, the Exome Variant Server, and an in-house exome variant database. The Lys293Glu variant is predicted to be pathogenic and affects a lysine residue that is conserved in different species. Variants in the PRDM5 gene were previously identified in anterior segment defects, i.e., autosomal recessive brittle cornea syndrome and keratoconus. The results of this study suggest that genetic variants in PRDM5 can lead to various syndromic and nonsyndromic disorders affecting the anterior segment of the eye.


Adaptive local refinement of the electron density, one-particle density matrices, and electron orbitals by hierarchical wavelet decomposition.
The common experience that the distribution and interaction of electrons widely vary by scanning over various parts of a molecule is incorporated in the atomic-orbital expansion of wave functions. The application of Gaussian-type atomic orbitals suffers from the poor representation of nuclear cusps, as well as asymptotic regions, whereas Slater-type orbitals lead to unmanageable computational difficulties. In this contribution we show that using the toolkit of wavelet analysis it is possible to find an expansion of the electron density and density operators which is sufficiently precise, but at the same time avoids unnecessary complications at smooth and slightly detailed parts of the system. The basic idea of wavelet analysis is a coarse description of the system on a rough grid and a consecutive application of refinement steps by introducing new basis functions on a finer grid. This step could highly increase the number of required basis functions, however, in this work we apply an adaptive refinement only in those regions of the molecule, where the details of the electron structure require it. A molecule is split into three regions with different detail characteristics. The neighborhood of a nuclear cusp is extremely well represented by a moderately fine wavelet expansion; the domains of the chemical bonds are reproduced at an even coarser resolution level, whereas the asymptotic tails of the electron structure are surprisingly precise already at a grid distance of 0.5 a.u. The strict localization property of wavelet functions leads to an especially simple calculation of the electron integrals.


Phenolic secondary metabolites from Acorus calamus (Acorales: Acoraceae) rhizomes: the feeding deterrents for Spodoptera litura (Lepidoptera: Noctuidae).
Spodoptera litura Fabricius (Lepidoptera: Noctuidae) is one of the most destructive pests of various crops cultivated in Thailand. Spodoptera litura larvae, at early stages, attack the leaves and feed on every part of infested crops in later stages. Acorus calamus essential oil contains toxic asarones, which are generalistic cytotoxic compounds. However, the present study is the first attempt to look at safer metabolites from the rhizomes that could deter insect feeding. The objective was to use such compounds as safer residues on crops that would prevent the feeding of herbivorous lepidopterans. Accordingly, phenolic metabolites were isolated and evaluated to establish the feeding deterrence against polyphagous S. litura larvae. Methanol extract of A. calamus, chrysin, and 4-hydroxy acetophenone compounds were the most effective feeding deterrents with FD50 of 87.18, 10.33, and 70.77 µg/cm2, respectively, after 4 h of feeding on treated kale leaves in a no-choice leaf disc assay. Chrysin also reduced carboxylesterase activities (1.37-fold), whereas A. calamus methanol extract reduced glutathione-S-transferase activities (1.44-fold). Some larvae were also seen dead if they consumed the treated kale leaves. Feeding deterrent activity in the methanol extract of A. calamus was due to chrysin and 4-hydroxy acetophenone. The large-scale utilization of such compounds could help develop feeding deterrent strategies in the integrated pest management of lepidopterans.


TLR7 Signaling Shapes and Maintains Antibody Diversity Upon Virus-Like Particle Immunization.
Virus-like particles (VLPs) are used in different marketed vaccines and are able to induce potent antibody responses. The innate pattern recognition receptors TLR7/8 recognize single stranded (ss) RNA naturally packaged into some VLPs and have been shown to enhance the production of IgG antibodies upon immunization. Here we demonstrate that, upon immunization with RNA-loaded bacteriophage-derived VLP Qβ, TLR7 signaling accelerates germinal center formation, promotes affinity/avidity maturation of VLP-specific IgG and isotype switching to IgG2b/2c. These findings extrapolated to antigens displayed on Qβ; as Fel d 1, the major cat allergen, chemically attached to Qβ also induced higher affinity/avidity IgG2b/2c antibodies in a TLR7-dependent fashion. Chimeric mice lacking TLR7-expression exclusively in B cells demonstrated that the enhanced IgG responses were driven by a B cell intrinsic mechanism. Importantly, deep sequencing of the BCR repertoire of antigen-specific B cells demonstrated higher diversity in mice with TLR7 signaling in B cells, suggesting that TLR7-signaling drives BCR repertoire development and diversity. Furthermore, the current data demonstrate that high levels of clonal diversity are reached early in the response and maintained by TLR7 signaling. In conclusion, TLR7 signaling enhances levels and quality of IgG antibodies, and this finding has major implications for vaccine design.


Fluorescent Sensor for Rapid Detection of Nucleophile and Convenient Comparison of Nucleophilicity.
Although nucleophile (Nu) is associated with many important chemical reactions, there are no fluorescence sensors for Nu detection and even for calculation of its nucleophilicity up to the present. In this study, we developed a fluorescent malononitrile-modified perylenediimide (MAPDI) which can selectively and rapidly react with nucleophiles, such as amines, amino acids, and some inorganic anions, and then change its UV-vis absorption and fluorescence emission. Detection limits of MAPDI for different nucleophiles could be calculated to compare their strength of nucleophilicity. Furthermore, it was found that MAPDI could detect reductive inorganic anions. These results suggested that MAPDI might have a great potential in organocatalytic reactions, metal ion-catalyzed reactions, reactions of amines, and other nucleophilic chemical reactions.


Simulated altitude exposure assessment by hyperspectral imaging.
Testing the human body's reaction to hypoxia (including the one generated by high altitude) is important in aeronautic medicine. This paper presents a method of monitoring blood oxygenation during experimental hypoxia using hyperspectral imaging (HSI) and a spectral unmixing model based on a modified Beer–Lambert law. A total of 20 healthy volunteers (males) aged 25 to 60 years were included in this study. A line-scan HSI system was used to acquire images of the faces of the subjects. The method generated oxyhemoglobin and deoxyhemoglobin distribution maps from the foreheads of the subjects at 5 and 10 min of hypoxia and after recovery in a high oxygen breathing mixture. The method also generated oxygen saturation maps that were validated using pulse oximetry. An interesting pattern of desaturation on the forehead was discovered during the study, showing one of the advantages of using HSI for skin oxygenation monitoring in hypoxic conditions. This could bring new insight into the physiological response to high altitude and may become a step forward in air crew testing.


Spirituality in nursing theory and practice: dilemmas for Christian bioethics.
Moral strangerhood is due in part to competing worldviews. The profession of nursing is experiencing a paradigm shift which creates ethical dilemmas for both Christian nurses and Christian patients. Nursing's new focus on spirituality and spiritual care presents itself as broadly defining a desired state or patient outcome -- spiritual integrity -- supposed to be applicable to all patients of all faiths. Analysis of nursing's definition of spirituality reveals assumptions and values consistent with an Eastern/New Age worldview which may cause hostility towards Christian patients stereotyped as dogmatic or noncompliant.


Exact recovery of sparse multiple measurement vectors by [Formula: see text]-minimization.
The joint sparse recovery problem is a generalization of the single measurement vector problem widely studied in compressed sensing. It aims to recover a set of jointly sparse vectors, i.e., those that have nonzero entries concentrated at a common location. Meanwhile [Formula: see text]-minimization subject to matrixes is widely used in a large number of algorithms designed for this problem, i.e., [Formula: see text]-minimization [Formula: see text] Therefore the main contribution in this paper is two theoretical results about this technique. The first one is proving that in every multiple system of linear equations there exists a constant [Formula: see text] such that the original unique sparse solution also can be recovered from a minimization in [Formula: see text] quasi-norm subject to matrixes whenever [Formula: see text]. The other one is showing an analytic expression of such [Formula: see text]. Finally, we display the results of one example to confirm the validity of our conclusions, and we use some numerical experiments to show that we increase the efficiency of these algorithms designed for [Formula: see text]-minimization by using our results.


Endozoochorous seed dispersal by Japanese macaques (Macaca fuscata): Effects of temporal variation in ranging and seed characteristics on seed shadows.
Variation in seed shadows generated by frugivores is caused by daily, seasonal, and inter-annual variation in ranging, as well as inter-specific variability in gut passage times according to seed characteristics. We studied the extent to which seed weight, specific gravity, and daily (morning, afternoon, and evening) and inter-annual (2004 vs. 2005) variation in ranging affected seed shadows generated by wild Japanese macaques (Macaca fuscata) in northern Japan. The macaques ingested fleshy fruits of 11 species during the two year study period; Viburnum dilatatum (Caprifoliaceae: heavier seeds with higher specific gravity) and Rosa multiflora (Rosaceae: lighter seeds with lower specific gravity) were eaten frequently in both years. The travel distances of macaques after feeding on V. dilatatum and R. multiflora fruits were estimated by combining feeding locations and ranging patterns measured in the field with gut passage times of model seeds in captive animals. Median travel distances after fruit feeding were 431 (quantile range: 277-654) and 478 m (265-646), respectively, with a maximum of 1,261 m. Neither year nor time of day affected travel distances. The gut passage time of model V. dilatatum seeds was longer than that of model R. multiflora seed, but this did not affect dispersal distances. Seed shadows for both species over 2 years showed unimodal distribution (peak: 101-500 m) and more than 90%, 20%, and 3% of ingested seeds were estimated to be dispersed >100, >500, and >1000 m, respectively, the longest known distances among macaque species. R. multiflora seeds tended to be dispersed further in 2004 than 2005, but V. dilatatum seeds were not, implying that inter-annual variations in ranging pattern due to the distribution and abundance of nut fruiting could affect dispersal distance.


How do children and adolescents of separated parents sleep? An investigation of custody arrangements, sleep habits, sleep problems, and sleep duration in Sweden.
An increasing number of children and adolescents divide their time between their separated parents' homes. Although marital conflict is disadvantageous for children's sleep, little is known about how children of separated parents sleep. The objective was to investigate the association between children's custody arrangements and sleep habits and sleep initiation difficulties. Cross sectional nationally representative samples of adolescents from the WHO study Health Behaviour in School-aged Children (HBSC) (n = 11,802). Sweden in 2013/2014 and 2017/2018. Adolescents in grades 5, 7, and 9 from Swedish compulsory comprehensive school. The survey included questions on sleep behaviors including bedtime, wake-up time and frequency of sleep onset problems. The analysis methods used were ordinary least squares and logistic regression. The results show differences by custody arrangement, but they are not uniform across the dependent variables. Children and adolescents in sole maternal custody were less likely to sleep as much as recommended (P < .001), more likely to have late bedtimes (P < .001), report sleep initiation difficulties (P < .01) and to report social jetlag between school mornings and weekends (P < .05) compared to those in 2-parent families. Shared physical custody was associated with a higher likelihood of late bedtimes (P < .05) and sleep initiation difficulties (P < .05) compared to those in 2-parent families, but not of sleeping less than recommended or reporting social jetlag. Less-than-equal sharing was generally associated with worse sleep than in 2-parent families. As custody arrangements seem to be associated with sleep, it is important to understand the mechanisms behind the findings.


Development and Implementation of Clinical Outcome Measures for Automated Collection Within Specialty Pharmacy Practice.
Johns Hopkins Specialty Pharmacy Services recognized the need to identify and develop standardized collection methods for clinical outcome measures (COMs) to demonstrate program quality and value to third-party payers, manufacturers, and internal stakeholders. To define specialty COMs and develop a framework for standardized data collection and reporting. COMs for specialty pharmacy disease states (cystic fibrosis; hepatitis C; inflammatory conditions in dermatology, gastroenterology and rheumatology; and multiple sclerosis) were identified through a literature search, collaboration with specialty pharmacists, and committee review. Once identified, these measures were distributed to internal and external stakeholders that included specialty clinic team members, drug manufacturers, and third-party payers for input and validation. A standardized process for discrete documentation and data collection of these measures was implemented using case management software, electronic medical record integration, and informatics support. 28 COMs were identified. The various data sources used to collect the COMs were incorporated into an automated virtual dashboard to allow for regular review and sharing with clinicians, leadership, and other key stakeholders. The virtual dashboard included COMs with data derived from electronic medical records (n = 9), patient-reported outcomes based on responses to pharmacist-delivered questions (n = 11), and pharmacist assessment of outcomes (n = 8). The completed virtual dashboard was further refined to allow for reporting of both population and patient-level outcome results on a quarterly basis. This project describes methods to standardize documentation, data collection, and reporting of clinical outcomes data for multiple specialty conditions in a health system-integrated specialty pharmacy program. Through literature review and stakeholder consultation, a variety of potential COMs were identified for further evaluation of feasibility and value considering documentation and data collection requirements. Incorporation of COMs into a virtual dashboard will help facilitate the evaluation of program effectiveness, quality improvement planning, and sharing with stakeholders. Additional opportunities exist to further standardize COMs across the pharmacy industry to allow for future benchmarking and standardized evaluation of patient care programs. No funding supported the writing of this article. The authors have no relevant conflicts of interest to disclose. This study was presented as a poster presentation at the APhA Annual Meeting, March 2018, Nashville, TN, and as a platform presentation at the Eastern States Conference, May 2018, Hershey, PA.


Quantification of ethanol's antipunishment effect in humans using the generalized matching equation.
Increases in rates of punished behavior by the administration of anxiolytic drugs (called antipunishment effects) are well established in animals but not humans. The present study examined antipunishment effects of ethanol in humans using a choice procedure. The behavior of 5 participants was placed under six concurrent variable-interval schedules of monetary reinforcement. In three of the six concurrent schedules, punishment, in the form of monetary loss, was superimposed on one alternative. Data were analyzed according to the generalized matching equation which distinguishes between bias (allocation of behavior beyond what matching to relative reinforcer densities would predict) and sensitivity to reinforcement (how well behavior tracks relative reinforcer densities). In addition, participants completed a pencil-tapping test. Under placebo punishment conditions, all participants demonstrated low response rates and a bias against the alternative associated with punishment, despite a resultant loss of available reinforcers. Bias against the punished alternative was dose-dependently reduced in participants shown to be most sensitive to ethanol (0.6, 1.2, and 1.8 g/kg) in measures of overall responding and on the pencil-tapping test. No ethanol-induced change in bias was noted when punishment was not imposed. Sensitivity to reinforcement also decreased for participants shown to be sensitive to ethanol. In addition to extending antipunishment effects to humans, these results also show that antipunishment effects can be quantified via the matching equation.


Estimating vaccine efficacy under the heterogeneity of vaccine action in a nonrandomly mixing population.
Vaccines often have heterogeneous actions because of possible variation in the immune systems of hosts. One must consider such heterogeneity of vaccine action when developing a vaccine efficacy parameter. Addressing this issue the summary model of vaccine action has been proposed in the literature to estimate vaccine efficacy in a randomly mixing population. However, nonrandom mixing is common, particularly in a small-group-mixing population. This article extends the summary model of vaccine action to such a nonrandomly mixing population. The interpretation and estimation of the summary vaccine efficacy were discussed in light of other two models of vaccine action: the leaky and all-or-nothing model. Vaccine efficacy under all models is defined as the relative reduction in transmission probability due to vaccine. Estimation of the transmission probabilities is described based on a deterministic epidemic model of an acute transmitted disease. This article further discusses, based on the above vaccine models, the estimation of vaccination coverage required to control epidemic. Methods are illustrated using data simulated by considering different patterns of mixing and vaccine action. Results confirm that the summary model performs better than other two models when vaccine action is heterogeneous.


Cost-effectiveness of cryoballoon ablation for the management of paroxysmal atrial fibrillation.
Cryoballoon ablation is an established treatment option for the management of patients with atrial fibrillation. We sought to evaluate the cost-effectiveness of cryoablation, compared with second-line anti-arrhythmic drug (AAD) therapy in patients with paroxysmal atrial fibrillation (PAF), from a UK payer perspective. We developed a state-transition (Markov) model to calculate the total costs and quality-adjusted life-years (QALYs) associated with cryoablation and AAD therapy in patients with PAF. A 5-year horizon was used for the base-case. Data from a recent study of cryoballoon ablation in patients with PAF were used to model short-term health outcomes and costs, together with longer term external evidence to populate subsequent time periods. Total discounted costs were £21 162 and £17 627 for the cryoballoon ablation and AAD arms, respectively. Total QALYs of 3.565 and 3.404 therefore led to an incremental cost-effectiveness ratio of £21 957 per QALY gained. Sensitivity analysis suggested that the key drivers of the results were the model time horizon, the costs of follow-up care in patients with recurrent AF, and the costs of the ablation procedure. Cryoballoon ablation provides increased quality-adjusted life expectancy compared with AAD at reasonable additional cost, representing good value for money in patients with PAF.


(111)In-exendin uptake in the pancreas correlates with the β-cell mass and not with the α-cell mass.
Targeting of the GLP-1 receptor with (111)In-labeled exendin is an attractive approach to determine the β-cell mass (BCM). Preclinical studies as well as a proof-of-concept study in type 1 diabetic patients and healthy subjects showed a direct correlation between BCM and radiotracer uptake. Despite these promising initial results, the influence of α-cells on the uptake of the radiotracer remains a matter of debate. In this study, we determined the correlation between pancreatic tracer uptake and β- and α-cell mass in a rat model for β-cell loss. The uptake of (111)In-exendin (% ID/g) showed a strong positive linear correlation with the BCM (Pearson r = 0.82). The fraction of glucagon-positive cells in the total endocrine mass was increased after alloxan treatment (26% ± 4%, 43% ± 8%, and 69% ± 21% for 0, 45, and 60 mg/kg alloxan, respectively). The uptake of (111)In-exendin showed a negative linear correlation with the α-cell fraction (Pearson r = -0.76). These data clearly indicate toward specificity of (111)In-exendin for β-cells and that the influence of the α-cells on (111)In-exendin uptake is negligible.


The Shan people's health beliefs, knowledge and perceptions of dengue in Eastern Shan Special Region IV, Myanmar.
Sustainable dengue intervention requires the participation of communities. Therefore, understanding the health beliefs, knowledge and perceptions of dengue among the local people can help to design locally appropriate strategies for effective interventions. A combination of qualitative semi-structured in-depth interviews (SDIs) and quantitative household questionnaire surveys (HHSs) was used to investigate the beliefs, knowledge and perceptions of dengue among the Shan people in Eastern Shan Special Region IV (ESSR4), Myanmar. The SDI was administered to 18 key informants, and the HHS was administered to 259 respondents. Only 14.7% (95% CI: 10.6-19.6%) of the HHS respondents could confirm that mosquitoes transmit dengue; 14.3% (95% CI: 10.3-19.1%) knew that piebald or Aedes mosquitoes transmit dengue; and 24.3% (95% CI: 19.2-30.0%) believed that dengue-transmitting mosquitoes mainly lived in small ponds. Merely ten (0.4%) of the 259 respondents of the HHS thought that dengue-transmitting mosquitoes bite in the day time. The people in the villages where there were outbreaks of dengue had more knowledge about dengue. This study demonstrates that the health beliefs of the Shan people were closely associated with their lifestyles, social and natural environments. To stay healthy, the Shan people clean their houses and surroundings regularly. However, their knowledge about dengue was not adequate for effective dengue control because it was mostly learned from previous dengue experiences and in a context that lacks systematic health education. Thus, in this setting, with a weak public health structure, more international support should be provided to promote the knowledge of the Shan people about dengue and to increase their sensitive awareness to dengue, which might be beneficial for social mobilization and community participation during future dengue prevention.


[Invasive fungal infections in patients with haematological malignancies].
Invasive fungal diseases represent an ever changing field within infectology, profoundly affecting daily clinical activities of specialists in haematology. The dynamic development seen in oncohaematology creates novel risk groups of patients, consequently necessitating a re-evaluation of principles in antifungal therapy from time to time. Not even in 2017 may achievements of fungal diagnostics and therapy become a substitute for clinical thinking and adaptation of general guidelines according to local experience. For antifungal management all centres should elaborate appropriate strategies. By creating and operating a multidisciplinary team, decision making can effectively be supported.


Human Lacrimal Production Rates from Modified Schirmer-Tear Test.
A simple methodology is presented to quantify basal tear production with a modified Schirmer-tear test. We introduce a simple clinical procedure to measure quantitative basal tear-production flowrates, QL, from a modified Schirmer-tear test (STT). Eight healthy subjects aged at least 18 years underwent modified STTs on both eyes for two visits each. Schirmer strips were sheathed with transparent tape before insertion. Topical anesthetic minimized reflex tearing. Wetting lengths were measured every 30 s for 5 min; QL was calculated from the linear slope of wetting length versus time. Determination of QL requires mass-balance equations on the tear prism and Schirmer strip with strip imbibition kinetics obeying Darcy and Young-Laplace laws. Basal tear production rates varied from essentially 0 to about 2 μl/min. With some exceptions, right and left eyes showed similar tear production rates. By following the modified STT, QL is established with minimal additional effort over a standard Schirmer test. We predict and observe four different subtypes of imbibition kinetics depending on how short or long the time is for first appearance of the wetting front and on how fast or slow is tear production. For slow lacrimal production rates, the standard 5-min wetting length does not correlate with basal tear production.


Specific antibody response of mice after immunization with COS-7 cell derived avian influenza virus (H5N1) recombinant proteins.
To develop avian influenza H5N1 recombinant protein, the hemagglutinin (HA), neuraminidase (NA), matrix (M), and non-structural (NS1) of avian influenza H5N1 isolates from Thailand were engineered to be expressed in prokaryotic (E. coli) and mammalian cell (COS-7) system. The plasmid pBAD-His and pSec-His were used as vectors for these inserted genes. Mice immunized with purified recombinant proteins at concentration 50-250 mug intramuscularly with Alum adjuvant at week 0, week 2, and week 3 showed a good immunogenicity measured by ELISA and neutralization assay. The HA and NS recombinant proteins produced in COS-7 cells can induce specific antibody titer detected by neutralization assay significantly higher than corresponding recombinant proteins produced in E. coli system. The antibody produced in immunized mice could neutralize heterologous avian influenza virus determined by micro-neutralization assay. This study shows that avian influenza virus H5N1 recombinant proteins produced in mammalian cell system were able to induce neutralizing antibody response.


Proceeding with care for successful prospective memory: Do we delay ongoing responding or actively monitor for cues?
In prospective memory (PM) research, costs (slowed responding to the ongoing task when a PM task is present relative to when it is not) have typically been interpreted as implicating an attentionally demanding monitoring process. To inform this interpretation, Heathcote, Loft, and Remington (2015), using an accumulator model, found that PM-related costs were associated with changes in a decision threshold parameter. This pattern was interpreted as disfavoring a monitoring process and supporting a non-capacity-consuming delayed responding strategy. The present study combined both behavioral and modeling techniques, as well as embedded parameter validation, to better illuminate the underlying processes involved in PM. We encouraged participants to use either a delayed responding or a monitoring strategy and used these conditions as anchor points for comparing a standard PM condition (with no strategy instructions). The monitoring strategy benefited PM more than did a delayed responding strategy. Most importantly, behaviors and modeling parameters associated with the standard PM instructions more closely reflected footprints of monitoring. Further, we found no individual model parameter that directly implicates monitoring behavior. (PsycINFO Database Record


Mercury Accumulation and Sequestration in a Deglaciated Forest Chronosequence: Insights from Particulate and Mineral-Associated Forms of Organic Matter.
Understanding mercury (Hg) complexation with soil organic matter is important in assessing atmospheric Hg accumulation and sequestration processes in forest ecosystems. Separating soil organic matter into particulate organic matter (POM) and mineral-associated organic matter (MAOM) can help in the understanding of Hg dynamics and cycling due to their very different chemical constituents and associated formation and functioning mechanisms. The concentration of Hg, carbon, and nitrogen contents and isotopic signatures of POM and MAOM in a deglaciated forest chronosequence were determined to construct the processes of Hg accumulation and sequestration. The results show that Hg in POM and MAOM are mainly derived from atmospheric Hg0 deposition. Hg concentration in MAOM is up to 76% higher than that in POM of broadleaf forests and up to 60% higher than that in POM of coniferous forests. Hg accumulation and sequestration in organic soil vary with the vegetation succession. Variations of δ202Hg and Δ199Hg are controlled by source mixing in the broadleaf forest and by Hg sequestration processes in the coniferous forest. Accumulation of atmospheric Hg and subsequent microbial reduction enrich heavier Hg isotopes in MAOM compared to POM due to the specific chemical constituents and nutritional role of MAOM.


Association between thyroid function and gallstone disease.
To investigate those associations using data of the population-based Study of Health in Pomerania. A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis. There were 385 persons (10.3%) with low (<0.3 mIU/L), 3 321 persons (88.6%) with normal and 43 persons (1.2%) with high serum TSH levels (>3 mIU/L). The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis (OR 3.77; 95%-CI 1.06-13.41; P<0.05). Also among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH (OR 1.40; 95%-CI 0.96-2.02; P = 0.07). In the female population, no such relation was identified. There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.


State-Level Implementation of Health and Safety Policies to Prevent Sudden Death and Catastrophic Injuries Within High Schools: An Update.
Mandated sports safety policies that incorporate evidence-based best practices have been shown to mitigate the risk of mortality and morbidity in sports. In 2017, a review of the state-level implementation of health and safety policies within high schools was released. To provide an update on the assessment of the implementation of health and safety policies pertaining to the leading causes of death and catastrophic injuries in sports within high school athletics in the United States. Cross-sectional study. A rubric composed of 5 equally weighted sections for sudden cardiac arrest, traumatic head injuries, exertional heatstroke, appropriate health care coverage, and emergency preparedness was utilized to assess an individual state's policies. State high school athletic/activities association (SHSAA) policies, enacted legislation, and Department of Education policies were extensively reviewed for all 50 states and the District of Columbia between academic year (AY) 2016-2017 (AY16/17) and 2019-2020 (AY19/20). To meet the specific rubric criteria and be awarded credit, policies needed to be mandated by all SHSAA member schools. Weighted scores were tabulated to calculate an aggregate score with a minimum of 0 and a maximum of 100. A total of 38 states had increased their rubric scores since AY16/17, with a mean increase of 5.57 ± 6.41 points. In AY19/20, scores ranged from 30.80 to 85.00 points compared with 23.00 to 78.75 points in AY16/17. Policies related to exertional heatstroke had the greatest change in scores (AY16/17 mean, 6.62 points; AY19/20 mean, 8.90 points; Δ = 2.28 points [11.40%]), followed by emergency preparedness (AY16/17 mean, 8.41 points; AY19/20 mean, 10.29 points; Δ = 1.88 points [9.40%]). A longitudinal review of state high school sports safety policies showed progress since AY16/17. A wide range in scores indicates that continued advocacy for the development and implementation of policies at the high school level is warranted.


Antifungal activity of chitosan against Aspergillus ochraceus and its possible mechanisms of action.
Chitosan is a polysaccharide with a wide-range antimicrobial spectrum and has been shown to be effective in control postharvest diseases of various fruit, but the possible mode of action is far from well known. In this study the antifungal activity of chitosan was tested on A. ochraceus and its possible mechanisms involved were also investigated both at microstructure and transcriptome level. Here, we found that chitosan could significantly inhibited spore germination and mycelia growth of A. ochraceus. Scan electron microscopy (SEM) and transmission electron microscopy (TEM) observations showed that chitosan induced remarkable changes in morphology and microstructure of hyphae, such as shriveling, abnormal branching and vacuolation. Changes in expression profiles of A. ochraceus upon chitosan treatment were analyzed by RNA sequencing and a total of 435 differentially expressed genes (DEGs) were identified. Further KEGG analysis revealed that DEGs involved in ribosome biogenesis were down-regulated, while DEGs related to membrane homeostasis, such as glycerophospholipid metabolism, ether lipid metabolism and steroid biosynthesis, were up-regulated. Chitosan may affect the growth and development of A. ochraceus by impairing the integrity of cell surface architecture and protein biosynthesis. These findings have practical implications with respect to the use of chitosan as an alternative way for controlling fungal pathogens.


Blood cardioplegia--a comparative clinical and laboratory study.
A prospective comparative study was undertaken to determine quality of myocardial preservation during open heart surgery by crystalloid and blood cardioplegic solutions. Total 55 consecutive patients were studied. Alternate patients received blood and crystalloid cardioplegia at random. Group I had 30 patients who received crystalloid cardioplegia, and group II, with 25 patients, received blood cardioplegia. The efficacy of two solutions was assessed by serum enzyme estimation of creatinine phosphokinase, M.B. fraction of creatinine phosphokinase and serum glutamate oxalate transferase (CPK, CPK-MB, SGOT), electron microscopic study of Left Ventricular biopsy and clinical assessment of post anoxic cardiac performance. Group II patients had lower serum enzyme levels, lesser microscopic myocardial damage, and better cardiac performance during immediate post-operative period, thus proving superiority of myocardial protection by blood cardioplegia.


On intrinsic equivalences of the finite helical axis, the instantaneous helical axis, and the SARA approach. A mathematical perspective.
Accurate determination of joint axes is essential for understanding musculoskeletal function. Whilst numerous algorithms to compute such axes exist, the conditions under which each of the methods performs best remain largely unknown. Typically, algorithms are evaluated for specific conditions only limiting the external validity of conclusions regarding their performance. We derive exact mathematical relationships between three commonly used algorithms for computing joint axes from motion data: finite helical axes (FHA), instantaneous helical axes (IHA) and SARA (symmetrical axis of rotation approach), including relationships for an extension to the mean helical axes methods that facilitate determining joint centres and axes. Through the derivation of a sound mathematical framework to objectively compare the algorithms we demonstrate that the FHA and SARA approach are equivalent for the analysis of two time frames. Moreover, we show that the position of a helical axis derived from the IHA using positional data is affected by a systematic error perpendicular to the true axis direction, whereas the axis direction is identical to those computed with either the FHA or SARA approach (true direction). Finally, with an appropriate choice of weighting factors the mean FHA (MFHA) method is equivalent to the Symmetrical Centre of Rotation Estimation (SCoRE) algorithm for determination of a Centre of Rotation (CoR), and similarly, equivalent to the SARA algorithm for determination of an Axis of Rotation (AoR). The deep understanding of the equivalences between methods presented here enables readers to choose numerically efficient, robust methods for determining AoRs and CoRs with confidence.


Rapid LC-MS/MS determination and pharmacokinetic application of linarin in rat plasma.
A sensitive, selective and robust liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the rapid determination of linarin in rat plasma. Separation of the analyte and warfarin as internal standard (IS) from 100 μL rat plasma was carried out by simple protein precipitation treatment. Chromatographic separation of the analyte was performed on a Diamonsil® C(18) column (150 × 4.6 mm, 5 µm) using isocratic mobile phase consisting of methanol-0.5% formic acid (80:20, v/v). The flow rate was 0.6 mL/min and the total run time was not more than 4.0 min. The method was validated over a wide dynamic concentration range of 1.00-1000 ng/mL for linarin. The precision and accuracy values for linarin met the acceptance criteria according to US Food and Drug Administration guidelines. Linarin was stable in the stability studies including a long-term test (-80°C for 43 days), a short-term test (ambient for 2 h and autosampler for 8 h) and three freeze-thaw cycles (-80-25°C). The developed assay method was applied to the pharmacokinetic study in rats after a single intramuscular administration of 713 µg/kg linarin.


Cross-link augmentation enhances CFR-PEEK short fixation in lumbar metastasis stabilization.
Introduction: Spinal stability plays a crucial role in the success of the surgical treatment of lumbar vertebral metastasis and, in current practice, less invasive approaches such as short constructs have been considered. Concurrently, carbon fiber-reinforced (CFR) poly-ether-ether-ketone (PEEK) fixation devices are expanding in oncologic spinal surgery thanks to their radiotransparency and valid mechanical properties. This study attempts to provide an exhaustive biomechanical comparison of different CFR-PEEK surgical stabilizations through a highly reproducible experimental setup. Methods: A Sawbones biomimetic phantom (T12-S1) was tested in flexion, extension, lateral bending, and axial rotation. An hemisome lesion on L3 vertebral body was mimicked and different pedicle screw posterior fixations were realized with implants from CarboFix Orthopedics Ltd: a long construct involving two spinal levels above and below the lesion, and a short construct involving only the levels adjacent to L3, with and without the addition of a transverse rod-rod cross-link; to provide additional insights on its long-term applicability, the event of a pedicle screw loosening was also accounted. Results: Short construct reduced the overloading onset caused by long stabilization. Particularly, the segmental motion contribution less deviated from the physiologic pattern and also the long-chain stiffness was reduced with respect to the prevalent long construct. The use of the cross-link enhanced the short stabilization by making it significantly stiffer in lateral bending and axial rotation, and by limiting mobiliza-tion in case of pedicle screw loosening. Discussion: The present study proved in vitro the biomechanical benefits of cross-link augmentation in short CFR-PEEK fixation, demonstrating it to be a potential alternative to standard long fixation in the surgical management of lumbar metastasis.


Good intentions and received wisdom are not good enough: the need for controlled trials in public health.
In the 1970s Archie Cochrane noted that many healthcare procedures and forms of organisation lacked evidence of effectiveness and efficiency, and argued for improved methods of evaluation, moving from clinical opinion and observation to randomised controlled trials (RCTs). His arguments gradually became accepted in medicine, but there has been considerable resistance among policymakers and researchers to their application to social and public health interventions. This essay argues that opposition to RCTs in public health is often based on a false distinction between healthcare and community settings, and sometimes on a misunderstanding of the principles of RCTs in health care. It suggests that just as in medicine, good intentions and received wisdom are not a sufficient basis for making public policy and allocating public funds for social or health improvement.


[A method of showing thermal effect of iron oxide nanoparticles in alternating magnetic field].
Ferromagnet has thermal effect in alternating magnetic field (AMF). Magnetically mediating hyperthermia is to localize magnetic substance within tumor tissue under AMF to promote the targeting ability and heat distribution of hyperthermia. This study was to develop a new method of showing the thermal effect of iron oxide Fe3O4 nanoparticles in AMF in vitro. Melted polyethelene glycol (PEG) was dropped on a slide to form crystal monolayer after cooling, and was covered with a bipartite blood coverslip. Certain amount of Fe3O4 powder (average diameter, 10 nm) was added in the gap of the blood coverslip to form a strip wandering on the slide with the width of 0.5-1.0 mm. This apparatus, named analog vessel bed, was then alternated in a 4.6 mT AMF at 100-250 kHz for 15 min. The changes of PEG crystal images were observed under micropolariscope. The thermal range of the heated Fe3O4 powder was affirmed according to melting status and melting point value of PEG crystal. In AMF, 5 mg of Fe3O4 could rise the temperature to above 45 degrees C-50 degrees C, which exceeded the required hyperthermic temperature 43 degree C; 15 mg of Fe3O4 could rise the temperature to no more than 59 degrees C-61 degrees C; while 25 mg of Fe3O4 could be heated up to 59 degrees C-61 degrees C. The PEG melting area was enlarged with the increasing Fe3O4 quantity or decreasing PEG melting point. The analog vessel bed apparatus could display the thermal effect of Fe3O4 nanoparticles in AMF, and would be helpful for further studies on effect of magnetically mediated hyperthermia on cancer cells.


HPV-16-related proteins as the serologic markers in cervical neoplasia.
Recently, a variety of HPV-related proteins have been synthesized and their utility as diagnostic and prognostic markers in cervical cancers needs to be assessed. The ability to generate preparative amounts of HPV-16 L1/L2 VLPs and E6, E7 proteins may have implications for the development of a serologic assay to detect anti-HPV-16 virion immune responses. The purpose of the study is to improve the way of proper management of the cervical cancer by investigating the utility of the recently developed HPV-16 L1/L2 VLPs, HPV-16 E6, E7 proteins as the clinical serologic markers through antibody reactions by comparison with those of SCCA and CEA which have been used as tumor markers for cervical cancer. The serologic responses in Korean women with cervical neoplasia by ELISA using HPV-16 L1/L2 VLPs and radioimmunoprecipitation assay (RIPA) using in vitro translated HPV-16 E6, E7 proteins were investigated. PCR using E6 type-specific primers for HPV-16/18 was used to determine the presence and type of HPV infection (normal controls, 15 cases; preinvasive lesions, 28 cases; invasive cervical cancers, 124 cases). The sera of 34% (42/124) of cervical cancers were positive for SCCA and the sera of 18% (22/124) of cervical cancers were positive for CEA. The positivity of SCCA was increased with advancing clinical stages, but the antibody levels were not correlated with clinical stage of disease. The sera of 7% (1/15) of normal controls, 39% (11/28) of preinvasive lesions, and 56% (70/124) of patients with cervical cancer were ELISA positive for HPV-16 L1/L2 VLPs (P < 0.05). The sera of 7% (2/28) of preinvasive lesions and 51% (63/124) of cervical cancers were positive for in vitro translated HPV-16 E6 protein (P < 0.05) and the sera of 11% (3/28) of preinvasive lesions and 33% (41/124) of cervical cancers were positive for in vitro translated HPV-16 E7 protein (P < 0.05). The antibody levels to HPV-16 E7 protein were correlated to clinical stage and tumor burden in a significant number of cervical cancers. These data suggest that a considerable number of patients with cervical neoplasia generated positive antibody response to L1/L2 VLPs and in vitro translated E6, E7 proteins of HPV-16. These HPV-16-associated proteins might be disease-specific markers which could be useful in an adjunctive diagnostic assay and a seroepidemiologic study of HPV-related cervical neoplasia. In particular, the monitoring of antibody to HPV-16 E7 protein seems to be valuable in the proper management of cervical cancers for specific tumor markers.


Weyl Semimetals as Hydrogen Evolution Catalysts.
The search for highly efficient and low-cost catalysts is one of the main driving forces in catalytic chemistry. Current strategies for the catalyst design focus on increasing the number and activity of local catalytic sites, such as the edge sites of molybdenum disulfides in the hydrogen evolution reaction (HER). Here, the study proposes and demonstrates a different principle that goes beyond local site optimization by utilizing topological electronic states to spur catalytic activity. For HER, excellent catalysts have been found among the transition-metal monopnictides-NbP, TaP, NbAs, and TaAs-which are recently discovered to be topological Weyl semimetals. Here the study shows that the combination of robust topological surface states and large room temperature carrier mobility, both of which originate from bulk Dirac bands of the Weyl semimetal, is a recipe for high activity HER catalysts. This approach has the potential to go beyond graphene based composite photocatalysts where graphene simply provides a high mobility medium without any active catalytic sites that have been found in these topological materials. Thus, the work provides a guiding principle for the discovery of novel catalysts from the emerging field of topological materials.


Large-scale transfection of mammalian cells for the fast production of recombinant protein.
Recombinant proteins (r-proteins) are increasingly important in fundamental research and for clinical applications. As many of these r-proteins are of human or animal origin, cultivated mammalian cells are the host of choice to ensure their functional folding and proper posttranslational modifications. Large-scale transfection of human embryonic kidney 293 or Chinese hamster ovary cells is now an established technology that can be used in the production of hundreds of milligram to gram quantities of a r-protein in less than 1 mo from cloning of its cDNA. This chapter aims to provide an overview of large-scale transfection technology with a particular emphasis on calcium phosphate and polyethylenimine-mediated gene transfer.


Evidence of Trichinella spiralis in Timis County, Romania: a report of a winter trichinellosis outbreak in 2008 due to consumption of contaminated pork.
A trichinellosis outbreak occurred in early 2008 in two villages in Timis County, Romania, due to consumption of pork from an infected animal. The infective species, detected by multiplex polymerase chain reaction, was Trichinella spiralis (Isolate Code ISS 1951). This report presents an extensive characterization of the outbreak using the documents of the epidemiological investigation and the medical charts of the hospitalized patients. Fifteen people consumed pork from the same backyard pig, which was slaughtered in the household without veterinary inspection of the meat. Among them, five patients presented clinical forms of the disease and were hospitalized. The analysis within this report includes only the hospitalized cases that were serologically confirmed. The mean age of the patients was 33.4 years. The common symptoms presented by these patients included headache, eyelid and lower limb edema, myalgia, fever, diarrhea, and nausea. Eosinophil counts ranged between 5.5% and 52%. Favorable outcomes were achieved for the patients using antihelminthic therapy. As an important public health concern, trichinellosis outbreaks reinforce the need to urgently implement veterinary and educational programs. Identification of T. spiralis in this case strengthens the supposition that it is one of the most frequently spread species in Romania.


Fractional Hofstadter States in Graphene on Hexagonal Boron Nitride.
In fractionally filled Landau levels there is only a small energy difference between broken translational symmetry electron-crystal states and exotic correlated quantum fluid states. We show that the spatially periodic substrate interaction associated with the long period moiré patterns present in graphene on nearly aligned hexagonal boron nitride tilts this close competition in favor of the former, explaining surprising recent experimental findings.


[Hemodynamic effects of 2 different doses of midazolam in combination with fentanyl for induction of anesthesia in surgery of the abdominal aorta].
The haemodynamic effects of anaesthetic induction with midazolam, fentanyl and pancuronium bromide were studied in two groups of patients undergoing abdominal aortic surgery: group A (10 patients receiving 0.2 mg X kg-1 midazolam) and group B (9 patients receiving 0.3 mg X kg-1 midazolam). Haemodynamic parameters were measured before induction after fluid loading and 15 min after induction. Heart rate, mean right atrial pressure, systemic and pulmonary vascular resistances, mean pulmonary wedge pressure and right ventricular stroke work index remained steady. On the other hand, mean arterial and pulmonary arterial pressures, systolic, cardiac and left ventricular stroke work indices fell significantly in both groups. However there was no statistically significant difference between the two groups.


Effects of allopurinol on beer-induced increases in plasma concentrations of purine bases and uridine.
We investigated the effects of allopurinol on beer-induced changes in the plasma concentration and urinary excretion of purine bases. Five healthy subjects underwent three studies: ingestion of beer after taking 300 mg allopurinol (combination study); ingestion of beer alone; ingestion of allopurinol alone. Increased plasma concentrations and urinary excretion of hypoxanthine were greater in the combination study than the beer alone study. However, increases in total plasma purine base concentrations were greater in the beer alone study, even though increases in plasma uridine concentrations did not differ. Beer-induced increases in plasma concentrations of purine bases appear partially offset by increased urinary excretion of hypoxanthine after allopurinol, which also controls increases in plasma uric acid levels caused by alcoholic beverage ingestion.


Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors.
Recombinant 5-hydroxytryptamine 5-HT7 receptors are known to express constitutive, i.e., agonist-independent activity. Nonselective ligands, like methiothepin, ritanserin or clozapine behave as full inverse agonists at 5-HT7 receptors. The aim of the present study was to evaluate the degree of inverse agonist activity of three selective 5-HT7 receptor antagonists ((R)-3,N-dimethyl-N-[1-methyl-3-(4-methyl-piperidin-1-yl)propyl]benzene sulfonamide or SB-258719, R-(+)-1-(toluene-3-sulfonyl)-2-[2-(4-methylpiperidin-1-yl)ethyl]-pyrrolidine or SB-258741 and (R)-3-(2-(2-(4-methylpiperidin-1-yl)ethyl)-pyrrolidine-1-sulfonyl)-phenol or SB-269970) in the same model. cAMP accumulation was measured in intact Chinese hamster ovary (CHO) cells expressing human recombinant 5-HT7a receptors. In these cells, 5-HT stimulated cAMP levels and a series of ligands antagonized the effect of 5-HT with a 5-HT7 receptor-like profile. SB-258719 had no inverse agonist activity, SB-258741 behaved as a partial inverse agonist and SB-269970 was a quasi-full inverse agonist (as compared to methiothepin). The inverse agonist effect of SB-269970 was antagonized in a concentration-dependent manner by SB-258719. The widespread spectrum of inverse agonist activities shown by these compounds should help assessing the physiological relevance of constitutive 5-HT7 receptor activity in native tissues.


Oxygen therapy via high flow nasal cannula in pediatric intensive care unit.
The aim of the present study was to assess the efficacy and safety of oxygen therapy via high flow nasal cannula in pediatric patients with acute respiratory failure. Patients who were admitted to pediatric intensive care unit and were administered high flow nasal cannula (HFNC) therapy between January 2015 and January 2016 were enrolled. Arterial blood gas parameters, respiratory rates (RR), heart rates (HR), systolic, db > iastolic, and mean arterial pressures (SBP, DBP, MAP), dyspnea scores, fractional oxygen indices (FiO < sub > 2 < /sub > ), and oxygen saturations (SatO < sub > 2 < /sub > ) were recorded at baseline, 30 minutes, and 12 hours. The study enrolled a total of 50 patients of whom 24 (48%) were female and 26 (52%) were male. Statistically significant reductions occurred in mean HR and RR values at 30 minutes and 12 hours compared to those at 0 minute (p < 0.05). Significant increases were observed in SatO2 values at 30 minutes (p.0.001) and 12 hours (p:0.005) compared to SatO2 value at 0 minute (p < 0.05). Similarly, there occurred significant reductions in mean FiO < sub > 2 < /sub > values at 30 minutes and 12 hours compared to baseline (p < 0.05). Significant reductions occurred in mean dyspnea score at 30 minutes (p:0.001) and 12 hours (p:0.001) compared to that at 0 minute (p < 0.05). pH, PaCO < sub > 2 < /sub > , PaO < sub > 2 < /sub > , SBP, and DBP values at 0 minute, 30 minutes, and 12 hours were not significantly different from one another (p > 0.05). No significant correlations were found between treatment failure and age at admission; mean pediatric index of mortality (PIM II), pediatric risk of mortality (PRISM), pediatric logistic organ dysfunction (PELOD) and pediatric multiple organ dysfunction score (P-MODS); and HR, RR, SatO2, pH, PaCO2, PaO2, SBP, DBP, MAP, FiO2 at baseline (p > 0.05). Therapy was successful in 40 (80%) patients whereas there occurred a need for invasive ventilation in 10 (20%) patients. High flow nasal oxygen therapy can be used for patients with acute severe hypoxemic respiratory failure without concurrent hypercapnia when adequate equipment and monitorization tools exist.


Measurement methods and algorithms for the management of solid nodules.
The increased detection of incidental small pulmonary nodules on multidetector computed tomography has driven attempts to refine the characterization and management of such nodules. A variety of methods have been developed to measure the size and biological activity of nodules to help define their nature, but these have limitations. Several clinical trials have assessed the efficacy of low-dose computed tomography screening for lung cancer and offer some insights into these limitations; however, they also provide evidence that refines existing nodule management strategies. This article reviews the size-based and functional measurement methods that can be used to predict the likelihood of malignancy in noncalcified solid pulmonary nodules and discusses their incorporation into existing algorithms for nodule management. The issue of multiple nodules and the optimum frequency and duration of follow-up are explored.


Proteomics and phosphoproteomics datasets of a muscle-specific STIM1 loss-of-function mouse model.
STIM1 is an ER/SR transmembrane protein that interacts with ORAI1 to activate store operated Ca2+ entry (SOCE) upon ER/SR depletion of calcium. Normally highly expressed in skeletal muscle, STIM1 deficiency causes significant changes to mitochondrial ultrastructure that do not occur with loss of ORAI1 or other components of SOCE. The datasets in this article are from large-scale proteomics and phosphoproteomics experiments in an inducible mouse model of skeletal muscle-specific STIM1 knock out (KO). These data reveal statistically significant changes in the relative abundance of specific proteins and sites of protein phosphorylation in STIM1 KO gastrocnemius. Protein samples from five biological replicates of each condition (+/- STIM1) were enzymatically digested, the resulting peptides labeled with tandem mass tag (TMT) reagents, mixed, and fractionated. Phosphopeptides were enriched and a small amount of each input retained for protein abundance analysis. All phosphopeptide and input fractions were analyzed by nano LC-MS/MS on a Q Exactive Plus Orbitrap mass spectrometer, searched with Proteome Discoverer software, and processed with in-house R-scripts for data normalization and statistical analysis. Article published in Molecular Metabolism [1].


Methods for molecular surveillance of influenza used in Macedonia.
To present and compare different Nucleic Acid Testing assays used for laboratory diagnosis of influenza virus infection in our country. Respiratory samples used were nose and throat swabs. The RNA extraction was performed with a QIAamp viral RNA kit. During the season 2009–2010 the first 25 samples were tested with: conventional gel-based RT-PCR and CDC rtRT-PCR using published specific matrix and HA gene primers and probes for influenza virus typing and subtyping. Of 25 samples tested with conventional RT-PCR 7(28%) were positive for influenza A, but negative for A/H1seasonal and A/H3. Retested with rtRT-PCR 9(36%) were positive for influenza A, 8(32%) were positive for А/H1pdm and 1(4%) was А/H3. Two samples positive with rtRT-PCR for influenza A were negative with RT-PCR. The sensitivity of the RT-PCR in comparison with rtRT-PCR is 100% and the specificity is 88.89%. Positive predictive value for RT-PCR is 77.78%, and negative predictive value is 100%. RT-PCR is a four-step and rtRT-PCR a one-step procedure. The turn-around time of RT-PCR is 6 hours and for rtRT-PCR it is 2 hours. For surveillance purposes nose and throat swabs are the more easy and practical to collect. It was proved that RT-PCR is too laborious, multi-step and time-consuming. The sensitivity of both assays is equal. The specificity of rtRT-PCR is higher. NAT assays for detection of influenza viruses have become an integral component of the surveillance programme in our country. They provide a fast, accurate and sensitive detection of influenza.


Grain size dependent transport and magnetoresistance behavior of chemical solution deposition grown nanostructured La0.7Sr0.3MnO3 manganite films.
Grain-size dependence of electronic transport and magnetoresistance (MR) properties of nanostructured La0.7Sr0.3MnO3 (LSMO) manganite thin films on LaAlO3 (100) single crystal substrates prepared using Chemical Solution Deposition (CSD) technique have been studied. The LSMO thin films were annealed at temperatures in the range of 700-1000 degrees C for different time intervals [6 h and 12 h] and crystallized as singlephase LSMO. Microstructural studies carried out using AFM show a marginal increase in the grain-size from 50 to 90 nm as the temperature was varied from 700 degrees C to 1000 degrees C respectively. It has been observed that the insulator-metal transition (T(p)) and MR depend on the grain size. In zero applied field, resistivity reduction is approximately 10(3) at 5 K for the films annealed at 700 degrees C [T(p) approximately 341 K] and 1000 degrees C [T(p) approximately 373 K]. MR versus H isotherms reveal that MR enhances in the vicinity of T(p) but decreases at low temperatures. The results obtained from the electronic and magnetotransport studies are in good agreement with the change in surface morphology of the films studied, which shows that the randomly distributed domains are composed of faceted grains. Synthesizing conditions, annealing temperature and time control the growth and alignment of grains into the domains, which cause better conduction at grain interface.


Experimental Observation of Interorbital Coupling.
Interorbital coupling refers to the possibility of exciting orbital states by otherwise orthogonal noninteracting modes, a forbidden process in photonic lattices due to intrinsic propagation constant detuning. In this Letter, using a femtosecond (fs) laser writing technique, we experimentally demonstrate that fundamental and excited orbital states can couple each other when located at different spatial positions. We perform a full characterization of an asymmetric double-well-like potential and implement a scan method to effectively map the dynamics along the propagation coordinate. Our fundamental observation also constitutes a direct solution for a spatial mode converter device, which could be located in any position inside a photonic glass chip. By taking advantage of the phase structure of higher-order photonic modes and the effective negative coupling generated, we propose a trimer configuration as a phase beam splitter, which could be of great relevance for multiplexing and interference-based photonic concatenated operations.


Gaze Gesture Recognition by Graph Convolutional Networks.
Gaze gestures are extensively used in the interactions with agents/computers/robots. Either remote eye tracking devices or head-mounted devices (HMDs) have the advantage of hands-free during the interaction. Previous studies have demonstrated the success of applying machine learning techniques for gaze gesture recognition. More recently, graph neural networks (GNNs) have shown great potential applications in several research areas such as image classification, action recognition, and text classification. However, GNNs are less applied in eye tracking researches. In this work, we propose a graph convolutional network (GCN)-based model for gaze gesture recognition. We train and evaluate the GCN model on the HideMyGaze! dataset. The results show that the accuracy, precision, and recall of the GCN model are 97.62%, 97.18%, and 98.46%, respectively, which are higher than the other compared conventional machine learning algorithms, the artificial neural network (ANN) and the convolutional neural network (CNN).


Social recognition memory: the effect of other people's responses for previously seen and unseen items.
When people discuss their memories, what one person says can influence what another person reports. In 3 studies, participants were shown sets of stimuli and then given recognition memory tests to measure the effect of one person's response on another's. The 1st study (n = 24) used word recognition with participant-confederate pairs and found that the effect of confederate responses on participant responses was larger for previously unseen items than for previously seen items (omega(p) = .23). This finding was replicated in the 2nd study, which used photographs of cars (n = 24). In the 3rd study (n = 54), which used photographs of faces with participant pairs, the effect was also larger for unseen items. Results indicate that people rely more on other people's memories for unremembered objects than for remembered objects. This is important for both theories of memory and applications (e.g., witnesses talking, students studying together).


Competing reaction model with many absorbing configurations.
We study a competitive reaction model between two monomers A and B on a linear lattice. We assume that monomer A can react with a nearest-neighbor monomer A or B , but reactions between monomers of type B are prohibited. We include in our model lateral interactions between monomers as well as the effects of temperature of the catalyst. The model is considered in the adsorption controlled limit, where the reaction rate is infinitely larger than the adsorption rate of the monomers. We employ site and pair mean-field approximations as well as static Monte Carlo simulations. We determine the phase diagram of the model in the plane y_{A} versus temperature, where y_{A} is the probability that a monomer of the type A arrives at the surface. This phase diagram shows regions of active and absorbing states separated by a line of continuous phase transitions. Despite the absorbing state of the model to be strongly dependent on temperature, we show that the static critical exponents of the model belong to the same universality class of the directed percolation.


Inverse association between number of teeth and left ventricular mass in women.
Recently, we have demonstrated a sex-specific inverse association between the number of teeth and hypertension. Left ventricular hypertrophy is a major cardiac sequel of hypertension. With the present study we sought to investigate whether there is also an inverse association between the number of teeth and left ventricular mass (LVM). We used data from 1913 subjects (1036 women and 877 men) who were recruited for the population-based Study of Health in Pomerania (SHIP). The number of teeth, with the exception of the third molars, was counted in the full mouth. LVM was determined echocardiographically. Multivariable analyses were adjusted for major confounders. Women with fewer teeth had higher values for LVM than women with more teeth. This association was stable when controlled for major confounders. In the full model, edentulous women had an adjusted LVM of 178.4 g [95% confidence interval (CI) 170.4, 186.3 g] while women with 24-28 teeth had an adjusted LVM of 164.8 g (95% CI 156.8, 172.9 g; P < 0.01). In men, no such differences were observed. We conclude that there is an association between the number of teeth and LVM in women aged 45 years or older. In women, these findings further explain why poor oral health predicts all-cause and circulatory mortality. Further research in young, low-risk populations is needed to explore this association in men.


Key importance of small RNA binding for the activity of a glycine-tryptophan (GW) motif-containing viral suppressor of RNA silencing.
Viruses express viral suppressors of RNA silencing (VSRs) to counteract RNA silencing-based host defenses. Although virtually all stages of the antiviral silencing pathway can be inhibited by VSRs, small RNAs (sRNAs) and Argonaute (AGO) proteins seem to be the most frequent targets. Recently, GW/WG motifs of some VSRs have been proposed to dictate their suppressor function by mediating interaction with AGO(s). Here we have studied the VSR encoded by Pelargonium line pattern virus (family Tombusviridae). The results show that p37, the viral coat protein, blocks RNA silencing. Site-directed mutagenesis of some p37 sequence traits, including a conserved GW motif, allowed generation of suppressor-competent and -incompetent molecules and uncoupling of the VSR and particle assembly capacities. The engineered mutants were used to assess the importance of p37 functions for viral infection and the relative contribution of diverse molecular interactions to suppressor activity. Two main conclusions can be drawn: (i) the silencing suppression and encapsidation functions of p37 are both required for systemic Pelargonium line pattern virus infection, and (ii) the suppressor activity of p37 relies on the ability to bind sRNAs rather than on interaction with AGOs. The data also caution against potential misinterpretations of results due to overlap of sequence signals related to distinct protein properties. This is well illustrated by mutation of the GW motif in p37 that concurrently affects nucleolar localization, efficient interaction with AGO1, and sRNA binding capability. These concomitant effects could have been overlooked in other GW motif-containing suppressors, as we exemplify with the orthologous p38 of turnip crinkle virus.


A review of maternally inherited diabetes and deafness.
Maternally inherited diabetes and deafness (MIDD), a mitochondrial disease first described in 1992, results from the mitochondrial DNA mutation and affects up to 1% of the patients with diabetes. This review discusses the biomedical mechanisms of MIDD patients; summarizes the recent improvement of clinical and genetic diagnosis of MIDD; outlines the advances of the clinical management of these patients and their families.


[Atrioventricular block in gynecologic-obstetric surgery].
Delivery ending with cesarotomy in women with A.-V.-block is thought to be the least hazardous. In cases where cardiac syncope occured before delivery, temporary cardiac pacemaker is applied. A complicated course of gynaecologic operation in a patient with permanent pacemaker on demand is described.


Untargeted screening of the bound / free phenolic composition in tomato cultivars for industrial transformation.
Tomato is one of the most important agricultural crops and it is characterized by a wide bioactive compound profile. However, little information is reported on its comprehensive polyphenol profile. In this work, 13 commercial tomato cultivars for industrial transformation were screened by ultra-high-pressure liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS) for both free and bound phenolic profiles. Thereafter, the in vitro antioxidant activity of each cultivar was assessed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance activity (ORAC) assays. Multivariate statistics, i.e. orthogonal projection to latent structures discriminant analysis (OPLS-DA), were then used to model samples according to their distinct phenolic signatures, thus providing compounds that better discriminated between the distributions of the cultivars that were considered. More than 350 phenolic compounds could be identified across the samples that were considered: flavonoids (such as flavones and flavanols), hydroxycinnamic acids, lignans, and lower-molecular-weight phenolics were the most frequently observed classes of phenolics in tomato berries. Anthocyanins were the most abundant class among bound phenolics (being highest in the Leader F1 and Defender F1 cultivars), followed by tyrosols (mainly in Heinz cultivars). However, flavones and hydroxybenzoic acids were the most represented discriminant phenolics in the bound fraction. Untargeted metabolomics allowed significant differences in phenolic composition to be outlined across the tomato cultivars that were analyzed. Such differences were particularly evident regarding the free-to-bound phenolic ratio, hence allowing differences in the bioaccessibility of phenolics to be postulated. © 2019 Society of Chemical Industry.


Detection of aspartate kinase in rat liver and its activation by Ca++ and calmodulin.
The enzyme aspartate kinase (EC 184.108.40.206) has been detected in rat liver (animal tissue) for the first time. This enzyme, like the aspartate kinase from bacteria and plants is inhibited by lysine and threonine. Further, the activity of the enzyme is stimulated over two fold by Ca++ and calmodulin and inhibited by EGTA, a Ca++ chelator and trifluoperazine, an anti-calmodulin compound.


ADHD and Everyday Life: Healthcare as a Significant Lifeline.
The aim of this qualitative study was to explore parental experiences of how healthcare practices and healthcare professionals in hospital clinics in Denmark influence everyday life of parents with a child with ADHD. The methodology was focused ethnography. Participant observation and interviews were used as the primary data collection methods. Fifteen families of children with ADHD were included from somatic and psychiatric hospital clinics. Three main themes emerged from the experiences of the families: When the house of cards collapses in everyday life, Treading water before and after receiving the ADHD diagnosis, and Healthcare as a significant lifeline. Accessibility to healthcare, trusting relationships and healthcare professionals recognizing how ADHD pervades all aspects of everyday life appear to be important factors in providing a lifeline for parents to help them regain confidence and control in disruptive phases. The parents depend on help from healthcare professionals and family-centred care to manage the complex challenges in everyday life.


Modifications in the seminal protein pattern and concentration among infertile men.
Lower concentrations of protein observed in semen of infertile men were mostly due to absence of vesicular proteins with higher isoelectric pH above pH 8.3. Two to four proteins with lower isoelectric pH showing electrophoretic mobility and originating both from seminal vesicle and prostate were absent in infertile semen samples. Concentrations of such proteins among oligozoospermic and azoospermic samples with complete maturation arrest and Sertoli cell only syndrome decreased mainly towards cathode, whereas, in vasectomized azoospermia the number of protein bands decreased both towards cathode and anode, though the concentration decreased mainly in the anodic proteins.


Long-Term Neurodevelopmental Impairment among Very Preterm Infants with Sepsis, Meningitis, and Intraventricular Hemorrhage.
Sepsis and intraventricular hemorrhage (IVH) are associated with poorer long-term neurodevelopmental outcomes in very preterm infants (VPIs), but less is known about the long-term effect of meningitis and the combined impact of both meningitis and IVH. Our objective was to examine the long-term neurodevelopmental outcomes of VPIs with late onset sepsis and meningitis, with and without IVH, in Canada. We conducted a retrospective cohort study of all infants <29 weeks GA who were admitted to 26 tertiary-level neonatal intensive care units in the Canadian Neonatal Network (CNN) and Canadian Neonatal Follow-Up Network (CNFUN) databases, from January 1, 2010, to December 31, 2016. Of the 6,322 infants in the cohort, 4,575 had no infection, 1,590 had late onset culture-positive bloodstream infection (CPBSI) only, and 157 had late onset meningitis. There was a significant (p < 0.05) trend of increasing rates of significant neurodevelopmental delay (sNDI) when comparing infants with no infection (sNDI rate 15.0%), late onset CPBSI (sNDI rate 22.9%), and late onset meningitis (sNDI rate 32.0%), even after adjustment for infant characteristics. Similar trends were observed for neurodevelopmental impairment, cerebral palsy, and individual Bayley-III scores <85 for cognitive, language, and motor development. There was an additive effect of IVH in all infant categories, but there was no multiplicative effect between IVH and late onset meningitis. There was an increasing trend of adverse neurodevelopmental outcomes when infants with no infection, late onset CPBSI and late onset meningitis are compared. IVH had an additive effect.


Mechanism and substrate specificity of telomeric protein POT1 stimulation of the Werner syndrome helicase.
Loss of the RecQ helicase WRN protein causes the cancer-prone progeroid disorder Werner syndrome (WS). WS cells exhibit defects in DNA replication and telomere preservation. The telomeric single-stranded binding protein POT1 stimulates WRN helicase to unwind longer telomeric duplexes that are otherwise poorly unwound. We reasoned that stimulation might occur by POT1 recruiting and retaining WRN on telomeric substrates during unwinding and/or by POT1 loading on partially unwound ssDNA strands to prevent strand re-annealing. To test these possibilities, we used substrates with POT1-binding sequences in the single-stranded tail, duplex or both. POT1 binding to ssDNA tails did not alter WRN activity on nontelomeric duplexes or recruit WRN to telomeric ssDNA. However, POT1 bound tails inhibited WRN activity on telomeric duplexes with a single 3'-ssDNA tail, which mimic telomeric ends in the open conformation. In contrast, POT1 bound tails stimulated WRN unwinding of forked telomeric duplexes. This indicates that POT1 interaction with the ssDNA/dsDNA junction regulates WRN activity. Furthermore, POT1 did not enhance retention of WRN on telomeric forks during unwinding. Collectively, these data suggest POT1 promotes the apparent processivity of WRN helicase by maintaining partially unwound strands in a melted state, rather than preventing WRN dissociation from the substrate.


Light and electron microscope structural study of the zona radiata in the oocyte of zebrafish (Danio rerio).
Teleosts account for more than half of the vertebrate species. A key feature of the evolutionary success of teleosts is their reproductive systems, which are efficient and functional under all aquatic environmental conditions. The zona radiata (ZR) is a non- cellular envelope over oolemma of teleost fish oocytes. The morphology of the ZR varies in different ovarian developmental stages and also among various fish species, which reflects adaptation to ecological conditions. In this research the structure of the ZR in the oocytes of zebrafish in different stages of ovarian development and oocyte growth were studied. The fish ovary was fixed in Bouin's solution. Histological sections were studied by light and scanning electron microscope after subjecting them to tissue preparation stages. In immature and primary growth stages (I and II), the ZR was not observed. In stage III, the ZR was observed as a thin layer around the oocyte. It increased in thickness at stage IV (vitellogenesis) but reduced in stage V (maturation). In early stage III, the ZR striations started to appear and in stage IV (vitellogenesis) fence-like striations were completely formed. SEM micrographs showed stria to be deep with crenelated margin. In late stage IV fence-like striations disappeared gradually and in matured egg (V) the stria turned into pit-like remnants. In zebrafish no adhesive filaments were observed and the ZR surface was smooth.


The serum homocysteine level in patients with acute ischemic stroke (AIS) after thrombolysis and its relationship with clinical outcomes.
The present study aims to investigate whether hyperhomocysteinemia (HHcy) affects the outcomes of the thrombolytic treatment for patients with AIS. A sample of 120 AIS patients were recruited and grouped according to their serum homocysteine (Hcy) levels. The National Institute of Health Stroke Scale (NIHSS) was obtained before treatment and 7 days after it to evaluate neurological outcomes; modified Rankin Scale (mRS) was obtained 12 weeks later to assess functional outcomes. Receiver operating characteristic curve (ROC) was used to demonstrate the relationship between serum Hcy level and the outcomes after tPA treatment. The serum Hcy level of 120 patients was of 27.57±20.17μmol/L. The NIHSS scores of the patients in the low Hcy level group were remarkably lower compared to those in the high-level group (p<0.05), after 7 days of treatment. In addition, the mRS scores of the patients in the low Hcy level group, after 12 weeks, were remarkably lower compared to those in the high-level group (p<0.01). ROC demonstrated that the serum Hcy level is related to the clinical outcomes of thrombolytic treatment with moderate specificity (80.3%) and sensitivity (58.2%). In conclusion, higher serum Hcy levels can indicate poorer clinical outcomes of thrombolytic treatment in patients with AIS.