Interaction between monensin and CCl4 after chronic treatment: dolichol and retinol content of rat liver sinusoidal cells.
The aim of this investigation was to study retinol, which is known to decrease in hepatic stellate cells during fibrogenesis, and dolichol, which influences membrane fluidity and decreases in liver injury, in freshly isolated liver parenchymal and nonparenchymal cells after intoxication of rats with CCl4 combined with the ionophore monensin for 3, 5 and 7 weeks. To study the interrelationship between dolichol and vitamin A transport, a load of vitamin A was given to batches of rats 3 days before sacrifice. Monensin did not modify the action of CCl4 in hepatocytes. On administration of CCl4 and CCl4-monensin, dolichol decreased independently of vitamin A load, while retinol increased, especially when a load of vitamin A was given to rats 3 days before sacrifice. Hepatocytes appeared to no longer be able to export or metabolize vitamin A. In a subfraction of hepatic stellate cells (Ito-1 cells) dolichol always decreased, while retinol was no longer stored after each treatment; dolichol and retinol showed the same behavior but the decrease was more pronounced in monensin after vitamin A load and after 3 weeks. These data support the hypothesis that by modulating membrane characteristics, dolichol might be involved in intracellular or intercellular retinol transport and that altered transport between hepatocytes and Ito-1 cells might accompany liver injury. The data regarding another subfraction, Ito-2 cells, partly resemble those for the Ito-1 fraction and are in agreement with the heterogeneity of hepatic stellate cells. In Kupffer and sinusoidal endothelial cells, dolichol and retinol content was not homogeneous and was only slightly altered after the treatments. Monensin and CCl4 are not interactive. Although both drugs alter membrane lipids, their association allows some sinusoidal cell responses to be differentiated.


Physical Violence Perpetration Among College Students: Prevalence and Associations With Substance Use and Mental Health Symptoms.
The aims of this study were to, first, report the prevalence of physical violence perpetration among a sample of college students and, second, to identify associations between physical violence perpetration, substance use, and mental health symptoms. We analyzed survey data from the Healthy Minds Study. We examined the 12-month prevalence of physical violence perpetration by gender identity from 2014-2019 (n = 181,056). We used multivariable logistic regression analyses to estimate associations between physical violence perpetration, substance use, and mental health symptoms from the 2018-2019 survey year (n = 43,563). Results revealed that 12-month prevalence rates of physical violence perpetration increased from 2014-2019 among male, female, and transgender/gender nonconforming college students. Results from multivariable logistic regression analyses using the 2018-2019 survey year revealed higher odds of physical violence perpetration in the previous 12 months among students who reported substance use and mental health symptoms, including vaping or e-cigarette use, illicit drug use, and nonsuicidal self-injury, among others. Our findings highlight steadily rising prevalence of physical violence perpetration from 2014-2019 among college students, indicating a growing need for more research and prevention efforts to address this problem in higher education settings. Efforts to prevent violence on college campuses should consider how to reduce substance use and improve mental health to reduce this form of violence.


[Rethinking the question of the favelas].
"This article intends to analyze some aspects of the evolution of Rio de Janeiro [Brazil]'s squatter settlements over the last decades with emphasis on: the improvement of its residential conditions, the growing diversification of its socio-economic activities and the consequent valorization of its space." (summary in ENG)


Major histocompatibility complex variants and articular disease severity in rheumatoid arthritis.
In the light of associations previously described between DR4, DQw7, the C4B null allele and Felty's syndrome, and between Dw14, the C4A null allele and rheumatoid vasculitis, we have looked for associations between these and other DRB1, DQB, DQA and C4 encoded variants, and articular disease severity assessed radiologically in 119 subjects with RA but without major extra-articular features. The association of DR4 with more severe disease and DR1 and DR2 with mild disease was confirmed but no associations were found between the presence of DQw7, Dw14, C4A or C4B null alleles and articular disease severity. This suggests that the associations noted previously between these markers and extra-articular disease features of Felty's syndrome or rheumatoid vasculitis are unlikely to reflect an overall effect on disease severity but more likely to represent associations with these particular extra-articular disease subsets.


Biophysical Informatics Approach For Quantifying Phenotypic Heterogeneity In Cancer Cell Migration In Confined Microenvironments.
Cancer cell heterogeneity can manifest genetically and phenotypically. Bioinformatics methods have been used to analyze complex genomics and transcriptomics data, but have not been well-established for analyzing biophysical data of phenotypically heterogeneous tumor cells. Here, we take an informatics approach to analyze the biophysical data of MDA-MB-231 cells, a widely used breast cancer cell line, during their spontaneous migration through confined environments. Experimentally, we vary the constriction microchannel geometries (wide channel, short constriction, and long constriction) and apply drug treatments. We find that cells in the short constriction are similar in morphology to the cells in the wide channel. However, their fluorescence profiles are comparable to those in the long constriction. We demonstrate that the cell migratory phenotype is correlated more to mitochondria in a non-confined environment and more to actin in a confined environment. We demonstrate that the cells' migratory phenotypes are altered by ciliobrevin D, a dynein inhibitor, in both confined and non-confined environments. Overall, our approach elucidates phenotypic heterogeneity in cancer cells under confined microenvironments at single-cell resolution. Here, we apply a bioinformatics approach to a single cell invasion assay. We demonstrate that this method can determine distinctions in morphology, cytoskeletal activities, and mitochondrial activities under various geometric constraints and for cells of different speeds. Our approach can be readily adapted to various heterogeneity studies for different types of input biophysical data. In addition, this approach can be applied to studies related to biophysical changes due to differences in external stimuli, such as treatment effects on cellular and subcellular activities, at single-cell resolution. Finally, as similar bioinformatics methods have been widely applied in studies of genetic heterogeneity, biophysical information extracted using this approach can be analyzed together with the genetic data to relate genetic and phenotypic heterogeneity. The data that support the findings of this study are available from the corresponding author upon reasonable request. Supplementary data are available at Bioinformatics online.


Closure of atrial septal defects in adult patients: justification of the "tipping point".
The "tipping point," favoring closure of hemodynamically significant atrial septal defects (ASDs) in the adult, has occurred and is supported by strong clinical data, especially in patients who present with symptoms. Echocardiographic evidence of right ventricular volume overload as a correlate of significant left-to-right intracardiac shunting remains a prerequisite to determine need for closure, even in patients with child-bearing potential. No patient appears too old to achieve benefit from closure of such defects. Modern therapeutics for pulmonary vascular disease may allow extension of these techniques to an increasingly threatened population, with care best coordinated and offered in appropriate centers of expertise.


Successful removal of a knotted fascia iliaca catheter: principles of patient positioning for peripheral nerve catheter extraction.
Peripheral nerve catheters are typically advanced a substantial distance into a perineural sheath, theoretically increasing the risk of catheter knotting and kinking. In this case report, we describe successful removal of a knotted fascia iliaca catheter and discuss principles of nonsurgical catheter extraction. A 64-yr-old woman with bilateral coxarthrosis presented for total hip arthroplasty under combined general/regional anesthesia. A 20-gauge fascia iliaca catheter was inserted before surgery by using a loss-of-resistance "double pop" technique. The catheter was uneventfully advanced 10 cm past the needle tip. After injection of 30 mL of 0.5% bupivacaine with 1:200,000 epinephrine and 100 microg of clonidine, general anesthesia was induced. An infusion of 0.1% bupivacaine at 20 mL/h was initiated in the recovery room for postoperative analgesia. Approximately 48 h later, resistance was encountered during catheter removal. Catheter extraction was attempted by altering patient positioning, including the supine position during which the catheter placement had occurred. Successful catheter removal was achieved by decreasing tension on the fascia lata and fascia iliaca through flexion of the hip joint and by applying firm, steady traction. The catheter was removed intact with a knot approximately 2 cm from the distal tip. We conclude that the principles for removal of entrapped peripheral catheters are not well known and may differ from those for neuraxial catheters. Patient positioning to minimize pressure and tension on the perineural soft tissues may facilitate catheter removal.


An immunoturbidimetric assay for canine C-reactive protein.
Antiserum was raised in sheep against canine C-reactive protein (CRP) and antibody, which was not specific for CRP, was removed by absorption with normal canine serum protein linked to agarose beads. The antiserum was used to develop an immunoturbidimetric assay for canine CRP on a MIRA (Roche Diagnostics) automated clinical biochemical analyser and assessed for routine analysis of CRP in canine serum samples. The assay gave standard curves with each standard having a coefficient of variance (CV) between 4.8 and 11%, interassay CVs below 11% and intra-assay CVs of less than 5%. Parallel dilution curves were obtained with purified CRP diluted in buffer and with endogenous CRP in serum diluted with buffer or with a serum with a negligible CRP content. The immunoturbidimetric assay results correlated with the results obtained using an ELISA method, r = 0.88. The immunoturbidimetric assay of canine CRP proved to be suitable for the routine analysis of canine CRP.


Feasibility and Variability of Automated Pupillometry Among Stroke Patients and Healthy Participants: Potential Implications for Clinical Practice.
Early neurological deterioration (END) is common after stroke and represents a poor prognostic marker. Manual pupillary assessment to detect END is subjective and has poor interrater reliability. Novel methods of automated pupillometry may be more reliable and accurate. This study aims to evaluate the acceptability and feasibility of automated pupillometry in patients with acute stroke and healthy volunteers and compare its interrater reliability with that of the traditional manual method. Automated and manual pupillary assessments were recorded between 2 independent observers alongside routine neurological observations from 12 acute stroke patients at a high risk of END. The proportion of completed measurements, adverse events, and qualitative feedback from patients and staff nurses was used to assess acceptability and feasibility of automated pupillometry. Paired automated and manual assessments were supplemented with measures from healthy volunteers to analyze measures of variability and agreement. Automated pupillometry was acceptable and safe among 12 acute stroke patients, but feasibility criteria were not attained. Interrater agreement for automated pupillometry was superior to manual assessment for measurements of pupil size, anisocoria, and pupillary light reactivity, for both patients and healthy volunteers. Substantial disparity existed in agreement between automated and manual assessments of these parameters. Automated pupillometry represents an alternative to manual pupillary assessment that may have greater interrater agreement and reliability. As an optimized method of neurological assessment, it has the potential to improve detection and treatment of conditions leading to END after stroke.


Raxofelast, a hydrophilic vitamin E-like antioxidant, stimulates wound healing in genetically diabetic mice.
Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of free radicals in the pathogenesis of diabetes-related healing deficit. This study assessed the effect of systemic administration of raxofelast, a protective membrane antioxidant agent, on wound healing by using healing-impaired (db/db) mice. The wound healing effect of raxofelast was investigated by using an incisional skin-wound model produced on the back of female diabetic C57BL/KsJ db+/db+ mice and their healthy littermates (db+/+m). Animals were then randomized to the following treatment: raxofelast (15 mg/kg/d intraperitoneally) or its vehicle (dimethyl sulfoxide/sodium chloride 0.9%, 1:1, vol/vol). The animals were killed on different days, and the wounded skin tissues were used for histologic evaluation and for analysis of malondialdehyde (MDA) level and myeloperoxidase (MPO) activity, wound breaking strength, and collagen content. Diabetic mice showed delayed wound healing together with low collagen content, breaking strength, and increased MDA levels and MPO activity when compared with their healthy littermates. The administration of raxofelast did not modify the process of wound repair in healthy (db/+) mice, but significantly improved impaired wound healing in diabetic mice through the stimulation of angiogenesis, reepithelialization, synthesis, and maturation of extracellular matrix. Furthermore, raxofelast treatment significantly reduced MDA levels, MPO activity, and increased the breaking strength and collagen content of the wound. The current study provides evidence that raxofelast restores wound healing to nearly normal levels in experimental diabetes-impaired wounds and suggests that an increased lipid peroxidation in diabetic mice may have a role in determining a defect of wound repair.


Collaborative helping: a practice framework for family-centered services.
This article offers a framework for collaborative family-centered practice that can rein-vigorate our work with families who have not responded to more traditional approaches. Collaborative Helping is grounded in family-centered principles that include: striving for cultural curiosity, believing in resourcefulness, working in partnership, and making our work more accountable to the clients we serve. The article introduces collaborative inquiry as an organizing metaphor for clinical practice and offers a five-step practice framework with clinical illustrations and sample questions. The framework draws from appreciative inquiry, motivational interviewing, the signs of safety approach to child protection work, and solution-focused and narrative therapies.


Cisplatin induces stemness in ovarian cancer.
The mainstay of treatment for ovarian cancer is platinum-based cytotoxic chemotherapy. However, therapeutic resistance and recurrence is a common eventuality for nearly all ovarian cancer patients, resulting in poor median survival. Recurrence is postulated to be driven by a population of self-renewing, therapeutically resistant cancer stem cells (CSCs). A current limitation in CSC studies is the inability to interrogate their dynamic changes in real time. Here we utilized a GFP reporter driven by the NANOG-promoter to enrich and track ovarian CSCs. Using this approach, we identified a population of cells with CSC properties including enhanced expression of stem cell transcription factors, self-renewal, and tumor initiation. We also observed elevations in CSC properties in cisplatin-resistant ovarian cancer cells as compared to cisplatin-naïve ovarian cancer cells. CD49f, a marker for CSCs in other solid tumors, enriched CSCs in cisplatin-resistant and -naïve cells. NANOG-GFP enriched CSCs (GFP+ cells) were more resistant to cisplatin as compared to GFP-negative cells. Moreover, upon cisplatin treatment, the GFP signal intensity and NANOG expression increased in GFP-negative cells, indicating that cisplatin was able to induce the CSC state. Taken together, we describe a reporter-based strategy that allows for determination of the CSC state in real time and can be used to detect the induction of the CSC state upon cisplatin treatment. As cisplatin may provide an inductive stress for the stem cell state, future efforts should focus on combining cytotoxic chemotherapy with a CSC targeted therapy for greater clinical utility.


Intracerebral Transplants of GMP-Grade Human Umbilical Cord-Derived Mesenchymal Stromal Cells Effectively Treat Subacute-Phase Ischemic Stroke in a Rodent Model.
In subacute and chronic phases of the stroke, there are no therapeutics available at present to promote functional recovery. Human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs) are one of the candidate cell types for treating subacute-phase stroke. The benefits of cell-based therapy largely depend on the migratory capacity of products administered, as well as their potential for engraftment in targeted tissues and paracrine activities. Timing and delivery modes may also influence the outcomes of stem-cell therapy. Still, the functional recuperative effects of differing hUC-MSC delivery modes, about cell replacement and cell-to-cell paracrine activity levels, have yet to be clarified in subacute phases of stroke.This study was conducted to compare the therapeutic effects of various delivery routes when administering Good Manufacturing Practice (GMP)-grade hUC-MSCs in a rodent model of subacute-phase stroke. Cell aliquots (1 × 106) were given to rats as intravenous (IV) injections or intracerebral (IC) transplants 1 week after middle cerebral artery occlusion (MCAo). Transplanted rats were examined up to 7 weeks later using various behavioral tests and immunohistochemical analyses. Most IC-transplanted cells survived for short periods (i.e., <4 weeks after receipt) and gradually disappeared, whereas IV-injected cells were undetectable in the brain at the same time points (i.e., 3 days, 4 weeks, or 7 weeks after injection). Although short-lived, IC-transplanted cells effectively improved behavioral deficits, serving to reduce infarct volumes and glial scar formation, increase subventricular counts of proliferating neuroblasts, and promote cerebrovascular ingrowth in ischemic penumbra regions. IV injection, however, failed to improve behavioral function or histologic parameters during the same 7-week time frame. These findings overall suggest that IC transplantation is preferable to IV injection for delivery of hUC-MSCs during subacute phases of stroke.


SEVE project (Surgical Expertise Validity Evaluation) risk adjusted quality by standard data.
The SEVE project (Surgical Expertise Validity Evaluation) is a collaborative effort of the AEC (Spanish Association of Surgeons) and the Section of Surgery of the European Union of Medical Specialists (UEMS) that aims to develop a model and an on line application that can be used to evaluate surgical complications. The aim is to identify the optimal results that can be obtained in each intervention, in order to present them as a reference for our usual practice (benchmarking).


The development of a high-density genetic map significantly improves the quality of reference genome assemblies for rose.
Roses are important woody plants featuring a set of important traits that cannot be investigated in traditional model plants. Here, we used the restriction-site associated DNA sequencing (RAD-seq) technology to develop a high-density linkage map of the backcross progeny (BC1F1) between Rosa chinensis 'Old Blush' (OB) and R. wichuraiana 'Basyes' Thornless' (BT). We obtained 643.63 million pair-end reads and identified 139,834 polymorphic tags that were distributed uniformly in the rose genome. 2,213 reliable markers were assigned to seven linkage groups (LGs). The length of the genetic map was 1,027.425 cM in total with a mean distance of 0.96 cM per marker locus. This new linkage map allowed anchoring an extra of 1.21/23.14 Mb (12.18/44.52%) of the unassembled OB scaffolds to the seven reference pseudo-chromosomes, thus significantly improved the quality of assembly of OB reference genome. We demonstrate that, while this new linkage map shares high collinearity level with strawberry genome, it also features two chromosomal rearrangements, indicating its usefulness as a resource for understanding the evolutionary scenario among Rosaceae genomes. Together with the newly released genome sequences for OB, this linkage map will facilitate the identification of genetic components underpinning key agricultural and biological traits, hence should greatly advance the studies and breeding efforts of rose.


Effects of Hydrothermal Pretreatment on the Structural Characteristics of Organosolv Lignin from Triarrhena lutarioriparia.
The effects of hydrothermal pretreatment (170⁻180 °C, 30⁻60 min) on the structural characteristics of enzymatic and extracted lignin from Triarrhena lutarioriparia (TL) during the integrated delignification process have been comprehensively investigated. Ion chromatography and NMR characterization showed that liquid products after mild hydrothermal process (170 °C, 30 min) were mainly composed of xylooligosaccharide (XOS) with different degrees of polymerization (DP ≥ 2). In addition, the structural changes of lignin during hydrothermal pretreatment and organic acid delignification process have been demonstrated by quantitative 2D heteronuclear single quantum coherence (2D-HSQC) and 31P-NMR techniques. Results showed that the structural changes of lignin (e.g., cleavage of β-O-4 linkages) induced by the hydrothermal pretreatment will facilitate the subsequent organic acid delignification process, and acetylated lignin could be obtained with a considerable yield, which can be used in lignin-based composite and candidate feedstock for catalytic upgrading of lignin. In short, the proposed process facilitates the producing of XOS and acetylated lignin for lignin valorization.


Interpretation of the LHCb P_{c}(4312)^{+} Signal.
We study the nature of the new signal reported by LHCb in the J/ψp spectrum. Based on the S-matrix principles, we perform a minimum-bias analysis of the underlying reaction amplitude, focusing on the analytic properties that can be related to the microscopic origin of the P_{c}(4312)^{+} peak. By exploring several amplitude parametrizations, we find evidence for the attractive effect of the Σ_{c}^{+}D[over ¯]^{0} channel, which is not strong enough, however, to form a bound state.


Discovery of Novel and Highly Potent Inhibitors of SARS CoV-2 Papain-Like Protease Through Structure-Based Pharmacophore Modeling, Virtual Screening, Molecular Docking, Molecular Dynamics Simulations, and Biological Evaluation.
Background and Objective: COVID-19 has struck our society as a great calamity, and the need for effective anti-viral drugs is more urgent than ever. Papain-like protease (PLpro) of SARS CoV-2 plays important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses, which is being regarded as a promising druggable target for the treatment of COVID-19. Here, we carried out a combined screening approach to identify novel and highly potent PLpro inhibitors for the treatment of COVID-19. Methods: We used a combined screening approach of structure-based pharmacophore modeling and molecular docking to screen an in-house database containing 35,000 compounds. SARS CoV-2 PLpro inhibition assay was used to carry out the biological evaluation of hit compounds. Molecular dynamics (MD) simulations were conducted to check the stability of the PLpro-hit complexes predicted by molecular docking. Results: We found that four hit compounds showed excellent inhibitory activities against PLpro with IC50 values ranging from 0.6 to 2.4 μM. Among them, the most promising compound, hit 2 is the best PLpro inhibitor and its inhibitory activity was about 4 times higher than that of the positive control (GRL0617). The study of MD simulations indicated that four hits could bind stably to the active site of PLpro. Further study of interaction analysis indicated that hit 2 could form hydrogen-bond interactions with the key amino acids such as Gln269 and Asp164 in the PLpro-active site. Conclusion: Hit 2 is a novel and highly potent PLpro inhibitor, which will open the way for the development of clinical PLpro inhibitors for the treatment of COVID-19.


Mechanisms of Resistance to Imatinib and Second-Generation Tyrosine Inhibitors in Chronic Myeloid Leukemia.
Targeted therapy in the form of selective tyrosine kinase inhibitors (TKI) has transformed the approach to management of chronic myeloid leukemia (CML) and dramatically improved patient outcome to the extent that imatinib is currently accepted as the first-line agent for nearly all patients presenting with CML, regardless of the phase of the disease. Impressive clinical responses are obtained in the majority of patients in chronic phase; however, not all patients experience an optimal response to imatinib, and furthermore, the clinical response in a number of patients will not be sustained. The process by which the leukemic cells prove resistant to TKIs and the restoration of BCR-ABL1 signal transduction from previous inhibition has initiated the pursuit for the causal mechanisms of resistance and strategies by which to surmount resistance to therapeutic intervention. ABL kinase domain mutations have been extensively implicated in the pathogenesis of TKI resistance, however, it is increasingly evident that the presence of mutations does not explain all cases of resistance and does not account for the failure of TKIs to eliminate minimal residual disease in patients who respond optimally. The focus of exploring TKI resistance has expanded to include the mechanism by which the drug is delivered to its target and the impact of drug influx and efflux proteins on TKI bioavailability. The limitations of imatinib have inspired the development of second generation TKIs in order to overcome the effect of resistance to this primary therapy. (Clin Cancer Res 2009;15(24):7519-27).


Diagnosis of Clostridium perfringens type C enteritis in pigs using a DNA amplification technique (PCR).
Clostridium perfringens type C, which produces alpha- and beta-toxin, causes severe haemorrhagic and necrotic enteritis in animals and humans. A polymerase-chain-reaction (PCR) assay was developed for the specific detection of the genes encoding alpha-, beta-, epsilon- and entertoxin of C. perfringens for rapid typing of C. perfringens strains, and especially for the identification of type C strains. Both the alpha- and beta-toxin genes were detected directly in porcine C. perfringens type C cultures and also in type B and type C collection strains to a sensitivity of 10(3) cells without purification of the DNA. The alpha-toxin gene was detected in all types of C. perfringens. The epsilon-toxin gene was found in type B and type D, and the enterotoxin gene in some type A strains. Nine other species of Clostridium and a variety of intestinal pathogenic bacteria showed no signal for these toxin genes in this PCR assay. The alpha- and beta-toxin genes PCR assay were used to identify C. perfringens strains isolated from intestinal contents of 36 necropsied piglets that had suddenly died or died after premonitory signs of diarrhoea. At necropsy, 20 piglets showed necrotizing enteritis (15 acute and 5 chronic cases) and were suspected to have suffered from a C. perfringens type C infection. All of them had C. perfringens which gave a positive PCR signal for alpha- and beta-toxin genes, and, hence, were identified as type C strains. From the 16 other piglets with lesions other than necrotizing enteritis, C. perfringens strains with the alpha-toxin gene, but no beta-toxin gene, were isolated.(ABSTRACT TRUNCATED AT 250 WORDS)


Dynamic 3D culture promotes spontaneous embryonic stem cell differentiation in vitro.
Spontaneous in vitro differentiation of mouse embryonic stem cells (mESC) is promoted by a dynamic, three-dimensional (3D), tissue-density perfusion technique with continuous medium perfusion and exchange in a novel four-compartment, interwoven capillary bioreactor. We compared ectodermal, endodermal, and mesodermal immunoreactive tissue structures formed by mESC at culture day 10 with mouse fetal tissue development at gestational day E9.5. The results show that the bioreactor cultures more closely resemble mouse fetal tissue development at gestational day E9.5 than control mESC cultured in Petri dishes.


Federal reimbursement of advanced practice nurses' services empowers the profession.
In recent years, advanced practice nurses have achieved authority for the direct payment of their services under the four federal health programs--Medicare, Medicaid, Civilian Health and Medical Program of Uniformed Services, and the Federal Employee Health Benefit Plan. This article describes the importance of direct reimbursement and the barriers that have been overcome in achieving reimbursement. It also gives an overview of how advanced practice nurse services are covered and paid for in the federal programs. Increased authority has positioned nurses as visible members of the health care team. Direct payment for advanced practice nurses' services promotes public visibility for their role as direct providers of primary care and as managers of their patients' plan of care. Our nation is in an era of health care reform where additional primary care practitioners are needed. Recognition of advanced practice nurses allows them to be seen as a solution to our nation's pressing need for more primary care providers.


Appraisal and coping in adults with cleft lip: associations with well-being and social anxiety.
The appraisal patterns and coping strategies of adults born with a cleft lip or cleft lip and palate were assessed in relation to measures of psychological well-being and social anxiety. A sample of 51 adults was recruited via the Cleft Lip and Palate Association. Data were collated using a questionnaire incorporating open questions and standardized measures. The focus was upon appraisal of the cleft, perceptions of consequences--both positive and negative--on personal and social dimensions, together with measurements of sense of coherence, psychological well-being, satisfaction with life and coping responses utilized in stressful situations. There was wide variability in the participants' reports of negative affect as a component of psychological well-being, suggesting that there may be small numbers of individuals with quite extreme responses. Seventy-five per cent reported difficulties which they attributed to their cleft. Perceiving positive gains as a result of the cleft and having a positive appraisal of facial appearance was associated with well-being. Patterns in coping strategies were also associated with emotional adjustment. Personal appraisals of both having a cleft and facial appearance may be more important in determining emotional well-being than the current medical emphasis on the aesthetics of surgical outcomes.


Antibodies to DNA in patients undergoing long-term hemodialysis.
It has been suggested that antibodies to native DNA occur with some frequency in patients treated by hemodialysis. This has been attributed to the use of the technique. We have investigated 48 patients on maintenance dialysis for the presence of antibodies to single stranded DNA (ss-DNA) and native DNA (n-DNA) compared to a control group of 25 nondialyzed patients with renal disease. In neither group of patients were antibodies to ss-DNA detected frequently. Antibodies to n-DNA were present in three of the dialyzed patients and in none of the control group. The frequency of antibodies in dialysis patients was insignificant in comparison to the same control group of non-dialyzed renal patients. There was no correlation between duration of dialysis and development of antibodies. A drug-induced lupus state is possible, but not established for two of the three patients on dialysis.


Revolutionizing treatment outcomes in hepatitis C: managed care implications and considerations--the new and evolving standards of care.
Although the prevalence of hepatitis C virus (HCV) infection is declining, overall costs associated with HCV infection and the burden of advanced liver disease are projected to increase. The recent approval of all-oral, fixed-dose combination treatments for patients with HCV infection has resulted in unprecedented rates of treatment success, and in debate regarding treatment costs and appropriation. With all-oral therapies becoming the standard of care for HCV infection, high drug costs and improved clinical outcomes-now including the eradication of disease-must be weighed when selecting the most appropriate therapy. Patient "warehousing" has reached an all-time high as payers and providers strive to strike the fine balance between clinical efficacy and cost-effectiveness of currently available treatments, and this "wait and see" period may very well continue until an acceptable balance has been achieved. As such, it is imperative that managed care clinicians maintain an informed understanding of the disease burden and current climate of HCV infection in the United States.


[miR-181a promotes the proliferation and metastasis of osteosarcoma cells by targeting RASSF1A].
To investigate the role of miR-181a in promoting the proliferation and metastasis of osteosarcoma cells by targeting RASSF1A. The level of miR-181a in 30 human osteosarcoma tissues and corresponding bone tissues was detected by real-time PCR, and the correlation between the level of miR-181a and clinicopathological characteristics of osteosarcoma was analyzed. Osteosarcoma cells MG-63 were transfected with chemically-synthesized miR-181a mimics and inhibitors, and the proliferation, migration and invasion of MG-63 cells were detected by MTT and Transwell assay. The specific binding ability of miR-181a to RASSF1A 3'-UTR was theoretically predicted and detected by the dual luciferase reporter gene assay. The level of miR-181a in osteosarcoma tissues was statistically higher than that in the corresponding bone tissues (P<0.001). However, the level of miR-181a was not correlated with gender, age, tumor size and stage (P>0.05). MTT and Transwell assays showed that the growth rate, migration and invasion ability of MG-63 cells with up-regulation of miR-181a was significantly increased compared with negative control (P<0.05), while the growth rate, migration and invasion ability of MG-63 with down-regulated miR-181a was significantly decreased compared with negative control (P<0.05). Luciferase reporter gene assay showed that miR-181a targeted the 3'-UTR of RASSF1A and regulated the expression of RASSF1A. MiR-181a promotes the proliferation and metastasis of osteosarcoma cells through specifically binding to RASSF1A 3'-UTR and subsequent down-regulation of RASSF1A.


Effect of social class of subjects on normative responses to TAT cards.
The present study investigated whether there are significant differences in the responses of individuals of varied social class background to selected TAT cards. White, female college students (N = 70) were classified as "working class" or "middle class" according to the characteristics of their families of origin and were asked to write stories in response to five TAT cards. Significant differences between the TAT stories written by the two social class groups were found for pattern of dependency and locus of control. No significant differences were found in number of drive expressions, intensity of drive expressions, or level of defenses used. Implications of these results for testing, as well as the difficulties in studying psychological phenomena across social class, are discussed.


Effects of sympathetic nerve stimulation on membrane potential in the circular muscle layer of mouse distal colon.
Little is known about the effects of sympathetic nerve stimulation on the membrane potential of colonic smooth muscle. In the distal colon of the mouse, intracellular microelectrodes were used to record the effects of lumbar colonic (LCN) and intermesenteric nerve (IMN) stimulation on circular muscle membrane potential in vitro. A two-compartment organ bath was used to selectively perfuse the colon and inferior mesenteric ganglion (IMG). In the presence of nifedipine (1-2 microM) (to the colonic compartment only), spontaneous depolarizations (myoelectric complexes, MCs) were recorded about every 4 min. MCs consisted of a prolonged burst of rapid oscillations in membrane potential (approximately 2 Hz) that were superimposed on a slow depolarization (mean amplitude 12 mV). Single electrical stimuli (600 microseconds duration) delivered to the LCN or IMN did not elicit a detectable change in the membrane potential. However, trains of stimuli (e.g., 60 pulses at 10-20 Hz) to the LCN or IMN during the intervals between MCs evoked a depolarization (with superimposed action potentials in the absence of nifedipine). Trains of stimuli delivered during the plateau phase of the MC reduced or abolished the rapid oscillations, without a further membrane depolarization. The MC period was unaffected by stimulation of the IMN or LCN. Responses were abolished by the selective perfusion of guanethidine (1 microM) to the colon, or by severing the LCN. Hexamethonium (500 microM) (to the colon) abolished MCs, induced sustained depolarization and attenuated the amplitude of the sympathetic depolarizations by 74%. In hexamethonium, sympathetic responses remained attenuated when the membrane of the circular muscle was repolarised by sodium nitroprusside (1 microM). Immunohistochemical studies of the colon revealed intense immunoreactivity for tyrosine hydroxylase in the myenteric plexus but not in the circular muscle layer. It is suggested that responses to sympathetic nerve stimulation in the circular muscle layer of the mouse colon are secondary to actions on the enteric nervous system.


Approaches to managing volunteer marrow donor registry HLA data. Algorithms for directing donor center-initiated HLA-DR typing of selected donors.
The German bone marrow donor center (DKMS) hasrecruited over 732 500 donors during the first 9 years of its existence. Initially, donors were typed for HLA-A and B, and DR typing was only done on request for a patient-initiated search. In 1994, a project was started which led to the donor center-initiated DR typing (DCI-DRT) of >35,000 donors. These donors were selected by donor-specific criteria (age, sex, height and weight) and according to HLA-A and B phenotypes. The latter was done to avoid unnecessary DR typing of the most common A, B phenotypes With a follow up of >6 years, this strategy has led to a number of confirmatory typings (CT) (n=4588) and stem cell harvests (n=568), which is at least comparable to those ensuing after patient-initiated HLA-DR typing (126 000 DR typings, 8,213 CTs, 888 resulting in stem-cell donation). DCI-DRT seems to be a cost-effective strategy which may help to reduce search times and improve search outcome, and improve the overall efficiency of donor center operations


Intensive versus traditional voice therapy for vocal nodules: perceptual, physiological, acoustic and aerodynamic changes.
To investigate the perceptual, physiological, acoustic, and aerodynamic outcomes of patients with vocal nodules following intensive voice treatment compared with traditional voice treatment. Pragmatic randomized clinical trial. Fifty-three women diagnosed with bilateral vocal nodules participated in the study. Voice recordings, stroboscopic recordings, acoustic, and aerodynamic assessments were made before voice treatment, after vocal hygiene education, and immediately postvoice treatment. All participants completed one session of vocal hygiene and eight sessions of direct voice therapy, however the delivery of the treatment between the two groups differed in treatment intensity. Physiological improvements were observed after vocal hygiene alone, whereas physiological, perceptual, and acoustic parameters all improved to some degree in both treatment groups immediately posttreatment. There were no differences in the extent of change observed between the two groups at any point following treatment. The investigation provided initial evidence that individuals with vocal nodules are able to recover voice function, vocal health, and vocal communication through intensive voice treatment. The results suggest comparable positive perceptual, physiological, and acoustic outcomes from intensive voice therapy compared with traditional voice therapy. Further investigation is required to determine the long-term effects of intensive treatment.


Frontal-Sensory Cortical Projections Become Dispensable for Attentional Performance Upon a Reduction of Task Demand in Mice.
Top-down attention is a dynamic cognitive process that facilitates the detection of the task-relevant stimuli from our complex sensory environment. A neural mechanism capable of deployment under specific task-demand conditions would be crucial to efficiently control attentional processes and improve promote goal-directed attention performance during fluctuating attentional demand. Previous studies have shown that frontal top-down neurons projecting from the anterior cingulate area (ACA) to the visual cortex (VIS; ACAVIS) are required for visual attentional behavior during the 5-choice serial reaction time task (5CSRTT) in mice. However, it is unknown whether the contribution of these projecting neurons is dependent on the extent of task demand. Here, we first examined how behavior outcomes depend on the number of locations for mice to pay attention and touch for successful performance, and found that the 2-choice serial reaction time task (2CSRTT) is less task demanding than the 5CSRTT. We then employed optogenetics to demonstrate that suppression ACAVIS projections immediately before stimulus presentation has no effect during the 2CSRTT in contrast to the impaired performance during the 5CSRTT. These results suggest that ACAVIS projections are necessary when task demand is high, but once a task demand is lowered, ACAVIS neuron activity becomes dispensable to adjust attentional performance. These findings support a model that the frontal-sensory ACAVIS projection regulates visual attention behavior during specific high task demand conditions, pointing to a flexible circuit-based mechanism for promoting attentional behavior.


CD81 costimulation skews CAR transduction toward naive T cells.
Adoptive cellular therapy using chimeric antigen receptors (CARs) has revolutionized our treatment of relapsed B cell malignancies and is currently being integrated into standard therapy. The impact of selecting specific T cell subsets for CAR transduction remains under investigation. Previous studies demonstrated that effector T cells derived from naive, rather than central memory T cells mediate more potent antitumor effects. Here, we investigate a method to skew CAR transduction toward naive T cells without physical cell sorting. Viral-mediated CAR transduction requires ex vivo T cell activation, traditionally achieved using antibody-mediated strategies. CD81 is a T cell costimulatory molecule that when combined with CD3 and CD28 enhances naive T cell activation. We interrogate the effect of CD81 costimulation on resultant CAR transduction. We identify that upon CD81-mediated activation, naive T cells lose their identifying surface phenotype and switch to a memory phenotype. By prelabeling naive T cells and tracking them through T cell activation and CAR transduction, we document that CD81 costimulation enhanced naive T cell activation and resultantly generated a CAR T cell product enriched with naive-derived CAR T cells.


Cell death by apoptosis is a feature of the rheumatoid nodule.
To examine the site and extent of apoptosis in the rheumatoid nodule and to determine whether this process make a significant contribution to the control of inflammation in the rheumatoid nodule as in other granulomas. Nine nodules and seven synovial membranes were examined by terminal deoxynucleotidyl transferase-mediated nick end labelling (TUNEL) in situ and a subset was further examined by DNA electrophoresis. The phenotype of apoptotic cells was identified using monoclonal antibodies and immunohistology. Apoptosis occurred in all zones of the nodule and, except in one case, was not focused adjacent to the necrotic centre. Apoptosis occurred in 3.5 (4.5)% (mean (SD)) of cells in the nodule and 3.6 (3.1)% of cells in synovial membranes. Apoptosis was more common in nodule T cells (4.1 (2.9)%) than fibroblasts (1.0 (1.4)%), p = 0.01. Among macrophages 3.2 (4.7)% were apoptotic. Banding of DNA consistent with apoptosis was seen in two of three nodules examined. Apoptosis occurs at a low level in the nodule, similar to the synovial membrane. The results suggest that two modes of cell death occur in the nodule: apoptosis, which occurs throughout the nodule; and necrosis, which is concentrated near the necrotic centre. Apoptosis was more common in infiltrating inflammatory cells than in resident fibroblasts. These results are consistent with the proposal that apoptosis of infiltrating inflammatory cells is important in controlling accumulation of cells in the rheumatoid nodule as has been established in experimental granulomas.


The multiple layers of signaling selectivity at protease-activated receptors.
The Protease-Activated Receptors (PARs) are G-protein-coupled receptors (GPCRs) characterized by a unique mechanism of activation. They carry built in their extended N-terminal structure their own activating agonist, in the form of a cryptic tethered ligand, unmasked by an irreversible proteolytic cleavage. Besides, PARs display several other particular properties, that converge and create interacting and intertwined layers of molecular processes regulating receptor's selective signaling with important biological and pharmacological consequences. These include the operation of multiple proteases, co-factors and protease inhibitors expressed in many types of cells and tissues, creating a dynamic balance between activators and inhibitors of PAR function in a tissue specific way. Membrane microdomain compartmentalization and allosteric modulation through intermolecular interactions between PARs adds further complexity to the receptor signaling and desensitization. Furthermore, molecular components interacting with thrombin and PARs take on new roles. In particular, activated protein C (APC) forms a significant negative feedback loop for thrombin with anticoagulant properties. In addition, APC exerts anti-inflammatory and direct neuroprotective effects in vivo and in vitro. This has informed the pharmacological dissection of anticoagulant from the anti-inflammatory and neuroprotective actions of APC and the generation of engineered APC mutations with diminished risk of serious bleeding, while preserving the cytoprotective effects of APC on cells. Even more important, these advances have made possible a paradigm shift, away from a "neurocentric" and towards a "vasculo-neuronal-inflammatory model of action", which supports novel pharmacological strategies targeting multiple disease mechanisms.


[Remarriage or cohabitation after divorce: the hypothesis of status integration].
"The aim of the research project is to assess which factors determine remarriage or cohabitation after divorce [in Belgium]. The research is based on data of 766 divorcees whose divorce took place in 1978. The chances of remarriage [or] cohabitation were evaluated using proportional hazard models and loglinear analysis. Special attention was paid to the effects of the number of children and age." (SUMMARY IN ENG AND FRE)


Recreational Cannabis Legalization in Canada: A Pediatrics Perspective.
Background: Despite its controversial nature, the use of recreational marijuana and cannabis-derived products continue to increase in popularity. Cannabis consumption is currently legal in certain American states as well as Canada, and it is also frequently used by Canadian youth. However, cannabis use during childhood and adolescence can contribute to significant harm. Materials andMethods: A review of current literature regarding the impacts of cannabis consumption among Canadian youth was conducted. Medline, Cochrane, Embase and PubMed databases were utilized to identify journal articles published within 10 years that highlighted the impacts of cannabis consumption in its different forms among the North American pediatric population. Results: Our review identified harms include structural and functional impairments in the developing brain, the development of mental health conditions such as depression and anxiety, impaired road safety while driving under the influence of cannabis, and the significant consequences of accidental ingestion of cannabis products by children. We also ascertained that cannabis cessation strategies that employed an affective model, which explores the root causes of adolescents turning to cannabis, are most effective in reducing substance use among adolescents. Conclusions: In light of the recent legalization of cannabis in Canada, the purpose of this article was to provide background on cannabis consumption and its legalization in Canada, the impacts of cannabis on Canadian youth, and evidence-based strategies to help mitigate them.


Right Foot Trans Metatarsal Amputation Following COVID-19 Infection.
A 60-year-old male patient with a prior coronavirus disease 2019 (COVID-19) pneumonia diagnosis presented with a right foot ulcer. The ulcer progressed to osteomyelitis of his right fifth metatarsal with eventual amputation and resection of the affected digit. The infection recurred two months later and spread to the right fourth metatarsal and gangrene, leading to the amputation and partial metatarsal head resection of the fourth toe. A month later, the infection recurred for a second time and a decision to perform a right trans metatarsal amputation of the foot was evaluated to avoid further progression of the infection and the need for more invasive surgical intervention.


Freud's dreams of reason: the Kantian structure of psychoanalysis.
Freud (and later commentators) have failed to explain how the origins of psychoanalytical theory began with a positivist investment without recognizing a dual epistemological commitment: simply, Freud engaged positivism because he believed it generally equated with empiricism, which he valued, and he rejected "philosophy," and, more specifically, Kantianism, because of the associated transcendental qualities of its epistemology. But this simple dismissal belies a deep investment in Kant's formulation of human reason, in which rationality escapes natural cause and thereby bestows humans with cognitive and moral autonomy. Freud also segregated human rationality: he divided the mind between (1) an unconscious grounded in the biological and thus subject to its own laws, and (2) a faculty of autonomous reason, lodged in consciousness and free of natural forces to become the repository of interpretation and free will. Psychoanalysis thus rests upon a basic Kantian construction, whereby reason, through the aid of analytic techniques, provides a detached scrutiny of the natural world, i.e. the unconscious mental domain. Further, sovereign reason becomes the instrument of self-knowing in the pursuit of human perfection. Herein lies the philosophical foundation of psychoanalytic theory, a beguiling paradox in which natural cause and autonomous reason - determinism and freedom - are conjoined despite their apparent logical exclusion.


Effects of Larval Nutrition on Wolbachia-Based Dengue Virus Interference in Aedes aegypti (Diptera: Culicidae).
In order to assess the broad-scale applicability of field releases of Wolbachia for the biological control of insect-transmitted diseases, we determined the relationship between the larval diet of Aedes aegypti L. mosquitoes infected with Wolbachia strains and their susceptibility to dengue virus (DENV) infection via intrathoracic injection and oral inoculation. Larvae were reared on diets that varied in the quantity of food which had the effect of modifying development time and adult body size. Wolbachia wMel infection was associated with highly significant reductions in dengue serotype 2 (DENV-2) infection rates of between 80 and 97.5% following intrathoracic injection of adults emerging from three diet levels. Reductions were 100% in two diet level treatments following oral inoculation. Similarly, wMelPop infection was associated with highly significant reductions in DENV-2 infection rates of between 95 and 100% for intrathoracic injection and 97.5 and 100% for oral inoculation across diet level treatments. Larval diet level had no significant effect on DENV-2 infection rates in the presence of Wolbachia infection in mosquitoes that were intrathoracically injected with the virus. This indicates that the effectiveness of Wolbachia on vector competence disruption within Ae. aegypti is unlikely to be compromised by variable larval nutrition in field settings.


Comprehensive molecular characterization of multifocal glioblastoma proves its monoclonal origin and reveals novel insights into clonal evolution and heterogeneity of glioblastomas.
The evolution of primary glioblastoma (GBM) is poorly understood. Multifocal GBM (ie, multiple synchronous lesions in one patient) could elucidate GBM development. We present the first comprehensive study of 12 GBM foci from 6 patients using array-CGH, spectral karyotyping, gene expression arrays, and next-generation sequencing. Multifocal GBMs genetically resemble primary GBMs. Comparing foci from the same patient proved their monoclonal origin. All tumors harbored alterations in the 3 GBM core pathways: RTK/PI3K, p53, and RB regulatory pathways with aberrations of EGFR and CDKN2A/B in all (100%) patients. This unexpected high frequency reflects a distinct genetic signature of multifocal GBMs and might account for their highly malignant and invasive phenotype. Surprisingly, the types of mutations in these genes/pathways were different in tumor foci from the same patients. For example, we found distinct mutations/aberrations in PTEN, TP53, EGFR, and CDKN2A/B, which therefore must have occurred independently and late during tumor development. We also identified chromothripsis as a late event and in tumors with wild-type TP53. Only 2 events were found to be early in all patients: single copy loss of PTEN and TERT promoter point mutations. Multifocal GBMs develop through parallel genetic evolution. The high frequency of alterations in 3 main pathways suggests that these are essential steps in GBM evolution; however, their late occurrence indicates that they are not founder events but rather subclonal drivers. This might account for the marked genetic heterogeneity seen in primary GBM and therefore has important implications for GBM therapy.


Early referral and comorbidity as possible causes of the declining transition rate in subjects at clinical high risk for psychosis.
A clinical high risk (CHR) for psychosis is regarded as the state of being at risk of developing psychosis. However, the rate of transition to psychosis among CHR subjects has been declining over time. We aimed to investigate the effects of the possible causes of the declining transition rate. A total of 129 CHR subjects were divided into two groups according to the date of enrollment: the 2005-2009 group and the 2009-2013 group. Baseline demographic and clinical characteristics, including medication prescription, were compared. The duration of untreated prodromal positive symptoms (DUPP) was used to account for early referral. The transition rate to psychosis in the 2009-2013 group was significantly lower than that in the 2005-2009 group (χ2 = 4.664, P = 0.031), although the risk factors of transition, intelligence quotient and prodromal positive symptoms did not differ between the two groups. When the DUPP was added to the follow-up duration, the between-group difference in the transition rates was no longer significant; however, the P-value was low (χ2 = 2.761, P = 0.097). After adjusting for axis II comorbidities other than schizotypal personality disorder, the effect of group division on the transition rate disappeared; however, the P-value was also low (P = 0.072). The mean olanzapine equivalent dose and the proportion of subjects prescribed with antidepressant or anxiolytic did not differ between the two groups. Early referral and axis II comorbidities other than schizotypal personality disorder were associated with the declining transition rate.


The Bedford-Stuyvesant/Crown Heights demonstration project.
The Bedford-Stuyvesant/Crown Heights demonstration project in Brooklyn, New York, provided Federal and New York State funds to offset the deficits of three hospitals and three freestanding health centers while the six institutions worked to improve service quality and financial viability of the local health care system. The demonstration project resulted in a merger between two of the participants: at the end of 1982, the Jewish Hospital and Medical Center of Brooklyn and St. John's Episcopal Hospital of Brooklyn merged to form Interfaith Medical Center.


Osthole Regulates Secretion of Pro-Inflammatory Cytokines and Expression of TLR2 and NF-κB in Normal Human Keratinocytes and Fibroblasts.
Osthole (OST), an active compound isolated from Cnidium monnieri, is used in traditional Chinese medicine to treat a variety of human diseases. Although OST has a good therapeutic effect, the underlying mechanism of its action in inflammatory skin diseases in humans is still unknown. The present study aimed to test the hypothesis that OST can be used as an herbal substance that minimizes skin inflammation and barrier dysfunction. In this study, histamine and LPS were used to induce inflammation in skin keratinocytes and fibroblasts to test whether OST can inhibit their responses. Cell migration was analyzed using a wound healing assay. Changes in cell monolayer integrity were assessed by the measurement of transepithelial electrical resistance. Secretion of IL-1β, IL-6, IL-8, TNF-α, CCL2/MCP-1, CCL5/RANTES, and COX-2 was measured by ELISA, while expression of TLR2, NF-κB, and COX-2 was analyzed by qPCR. OST decreased the level of IL-1β, TNF-α, CCL2/MCP-1 and CCL5/RANTES, and expression of TLR2, NF-κB and COX-2 during histamine/LPS-induced inflammation in human keratinocytes and fibroblasts. OST also improved cell migration and cell barrier function. Our results suggest that OST suppresses inflammatory responses via regulation of IL-1β, TNF-α, CCL2/MCP-1 and CCL5/RANTES secretion, and TLR2, and COX-2 expression.


Lung hyperinflation by mechanical ventilation versus isolated tracheal aspiration in the bronchial hygiene of patients undergoing mechanical ventilation.
To determine the efficacy of lung hyperinflation maneuvers via a mechanical ventilator compared to isolated tracheal aspiration for removing secretions, normalizing hemodynamics and improving lung mechanics in patients on mechanical ventilation. This was a randomized crossover clinical trial including patients admitted to the intensive care unit and on mechanical ventilation for more than 48 hours. Patients were randomized to receive either isolated tracheal aspiration (Control Group) or lung hyperinflation by mechanical ventilator (MVH Group). Hemodynamic and mechanical respiratory parameters were measured along with the amount of aspirated secretions. A total of 50 patients were included. The mean age of the patients was 44.7 ± 21.6 years, and 31 were male. Compared to the Control Group, the MVH Group showed greater aspirated secretion amount (3.9g versus 6.4g, p = 0.0001), variation in mean dynamic compliance (-1.3 ± 2.3 versus -2.9 ± 2.3; p = 0.008), and expired tidal volume (-0.7 ± 0.0 versus -54.1 ± 38.8, p = 0.0001) as well as a significant decrease in peak inspiratory pressure (0.2 ± 0.1 versus 2.5 ± 0.1; p = 0.001). In the studied sample, the MVH technique led to a greater amount of aspirated secretions, significant increases in dynamic compliance and expired tidal volume and a significant reduction in peak inspiratory pressure.


Working time preferences and early and late retirement intentions.
Career decisions are based on the fit between an individual and his/her environment. This study explores the effect of person-environment fit regarding actual and preferred weekly working hours on early and late retirement intentions in a sample of 7,859 employees aged 50 to 65 years of age living in Germany. Findings from multinomial logistic regression analysis show that a preferred decrease in working hours was associated with an increased risk for early retirement compared to regular retirement intentions (OR = 1.82). A preferred increase in working hours was associated with higher odds for a late career (OR = 1.87).


The effect of abdominal radiation on spleen function: a study in children with Wilms' tumor.
Reports of splenic dysfunction in patients with Hodgkin's disease who received radiation therapy to the spleen raise questions concerning impairment of splenic function and the long-term risk of bacterial sepsis in children who receive abdominal radiation for other diseases. Splenic function was studied in 20 children with Wilms' tumor using a quantitative assessment of vacuolated ("pitted") red cells as a measure of reticuloendothelial function. Fourteen children had received abdominal radiation to a field involving the spleen at a median dose of 2000 rads. Their pitted red cells counts were no different from those of 6 children who received therapy without radiation to the spleen or to those of a group of normal children and adults. We conclude that there is no demonstrable long-term impairment of spleen function with radiation doses at or below 2200 rads.


Taxonomy of the genus Leishmania: present and future trends and their implications.
The application of different taxonomic methods (Cladistic, Evolutionary Taxonomy and Numerical Taxonomy) to the taxonomy of the Genus Leishmania are reviewed. The major groupings of the most recent classifications obtained using the cladistical approach agree with the major divisions of previous classifications which used traditional taxonomy (Evolutionary Taxonomy). The advantage of the cladistical approach is that it produces cladograms whose branches indicate more accurately levels of relationships between the different taxa. Numerical Taxonomy is useful for identification but not as good as the cladistical approach for classification. The ancient division of this monophyletic genus into two major evolutionary lines supports the use of the subgeneric names Leishmania and Viannia.


Limited Lithium Loading Promises Improved Lithium-Metal Anodes in Interface-Modified 3D Matrixes.
Confining Li metal in a three-dimensional (3D) matrix has been proven effective in improving the Li-metal anodes; however, in most studies, the loading of Li in the 3D matrix is far excessive, resulting in a dense bulk Li-metal anode with a low Li-utilization rate, forfeiting the effect of the 3D matrix. Here, we show that limiting the loading of Li metal within an interface-modified 3D carbon matrix not only increases the Li-utilization rate but also improves the electrochemical performance of the Li-metal anode. We use lithiophilic Fe2O3 granules anchored on a 3D carbon fiber scaffold to guide molten Li dispersion onto the fibers with controlled Li loading. Limiting Li loading maximizes the interface lithiophilic effect of the Fe2O3 granules while preserving sufficient space for electrolyte infusion, collectively ensuring uniform Li deposition and fast Li+ transport kinetics. The Li anode with limited Li dosage achieves remarkably improved Li-anode performances, including long lifespan, low voltage polarization, and low electrochemical resistance in both the symmetric cells and full cells. The improved electrochemical performance of the limited Li anode substantiates the importance to reduce Li loading from a fresh perspective and provides an avenue for building practical Li-metal batteries.


Diterpene biosynthesis in maize seedlings in response to fungal infection.
A cell-free system which catalyzes the biosynthesis of terpene hydrocarbons when supplemented with mevalonate, Mn(2+), and ATP was prepared from the scutellum-embryonic axis region of maize seedlings. The capacity of this system for the production of terpene hydrocarbons was enhanced 50- to 100-fold when the seedlings were exposed for 48 hours to the fungus Rhizopus stolonifer prior to tissue homogenization. The fungi Aspergillus niger, Fusarium moniliforme, and Verticillium albo-atrum also elicited this biosynthetic enhancement. The terpene hydrocarbon products were separable into six fractions by argentation thin layer chromatography. Radioactivity was contributed to five of these fractions when either geranylgeranyl pyrophosphate or copalyl pyrophosphate was supplied as substrate, suggesting that polycyclic diterpenoid hydrocarbons were the main products. Large scale biosynthetic reactions led to the acquisition of about 1 milligram of terpene hydrocarbon products plus some more polar terpenoid products. Analysis of the hydrocarbon products by gas chromatography and mass spectrometry led to the separation of six distinct diterpene hydrocarbons plus a fraction with a molecular weight of about 550. Three of the diterpene hydrocarbons were identified as kaur-16-ene, kaur-15-ene (isokaurene), and pimara-8(14),15-diene. None of the terpene hydrocarbon fractions tested displayed antifungal activity in the Cladosporium cucumerinum thin layer plate assay.


Complete and Incomplete Genome Packaging of Influenza A and B Viruses.
The genomes of influenza A and B viruses comprise eight segmented, single-stranded, negative-sense viral RNAs (vRNAs). Although segmentation of the virus genome complicates the packaging of infectious progeny into virions, it provides an evolutionary benefit in that it allows viruses to exchange vRNAs with other strains. Influenza A viruses are believed to package their eight different vRNAs in a specific manner. However, several studies have shown that many viruses are noninfectious and fail to package at least one vRNA. Therefore, the genome-packaging mechanism is not fully understood. In this study, we used electron microscopy to count the number of ribonucleoproteins (RNPs) inside the virions of different influenza A and B virus strains. All eight strains examined displayed eight RNPs arranged in a "7+1" configuration in which a central RNP was surrounded by seven RNPs. Three-dimensional analysis of the virions showed that at least 80% of the virions packaged all eight RNPs; however, some virions packaged only five to seven RNPs, with the exact proportion depending on the strain examined. These results directly demonstrate that most viruses package eight RNPs, but some do indeed package fewer. Our findings support the selective genome-packaging model and demonstrate the variability in the number of RNPs incorporated by virions, suggesting that the genome-packaging mechanism of influenza viruses is more flexible than previously thought. The genomes of influenza A and B viruses contain segmented RNAs, which complicates genome packaging but provides the evolutionary advantage of allowing the exchange of individual genome segments with those of other strains. Some studies have shown that influenza A viruses package all eight genome segments in a specific manner, whereas others have shown that many virions are noninfectious and fail to package at least one genome segment. However, such viruses have never been directly observed. Here, we used electron microscopy to provide the first direct visual evidence of virions packaging an incomplete set of ribonucleoproteins. The percentage of these noninfectious virions varied from 0 to 20, depending on the virus strain, indicating that most virions package all eight genome segments. These results extend our knowledge about how infectious and noninfectious virions coordinate for successful virus infection.


Combining scalp tissue expansion with porous polyethylene total ear reconstruction in burned patients.
Burned ear reconstruction remains one of the most difficult areas of plastic surgery. A superior result is needed to justify the donor site morbidity when reconstructing with a costochondral graft. Recently, more studies have evaluated porous polyethylene ear reconstruction in microtia and in burns. A total loss of the pinna from burns is rare and often associated with significant alopecia. Tissue expansion is an excellent means of reconstructing burned scalp alopecia. Deeply burned skin is often so densely scarred that a costochondral graft would produce a nondescript scarred mass with little resemblance to the native ear. This mini series overview describes 3 cases of porous polyethylene and total ear reconstructions done in conjunction with tissue expansion reconstruction for burn alopecia. This method can be used as a very efficient combination of procedures in a severely burned patient without the additional morbidity of costochondral grafting.This is the first description of this combination of procedures. At the initial procedure, a large tissue expander is placed beneath the hair-bearing scalp in a subgaleal plane. At the time of tissue expander removal and alopecia resection, a temporoparietal fascia flap is elevated. The incisions for alopecia resection allow easy dissection behind the external auditory meatus. The porous polyethylene construct is then placed posteriorly and wrapped with the temporoparietal fascial flap. The hairline is reconstructed simultaneously. The technique described makes full use of the temporoparietal fascial flap that may, otherwise, be resected or injured with the alopecia resection. It also allows alopecia reconstruction and accomplishes 2 reconstructive goals at once with little or no donor site morbidity.


Biorefinery of Biomass of Agro-Industrial Banana Waste to Obtain High-Value Biopolymers.
On a worldwide scale, food demand is increasing as a consequence of global population growth. This makes companies push their food supply chains' limits with a consequent increase in generation of large amounts of untreated waste that are considered of no value to them. Biorefinery technologies offer a suitable alternative for obtaining high-value products by using unconventional raw materials, such as agro-industrial waste. Currently, most biorefineries aim to take advantage of specific residues (by either chemical, biotechnological, or physical treatments) provided by agro-industry in order to develop high-value products for either in-house use or for sale purposes. This article reviews the currently explored possibilities to apply biorefinery-known processes to banana agro-industrial waste in order to generate high-value products out of this residual biomass source. Firstly, the Central and Latin American context regarding biomass and banana residues is presented, followed by advantages of using banana residues as raw materials for the production of distinct biofuels, nanocellulose fibers, different bioplastics, and other high-value products Lastly, additional uses of banana biomass residues are presented, including energy generation and water treatment.


Bifidobacterium moukalabense sp. nov., isolated from the faeces of wild west lowland gorilla (Gorilla gorilla gorilla).
Gram-staining-positive anaerobic rods were isolated from the faeces of a wild lowland gorilla (Gorilla gorilla gorilla) in Moukalaba-Doudou National Park, Gabon, and strain GG01(T) was taxonomically investigated. Based on phylogenetic analyses and specific phenotypic characteristics, the strain belonged to the genus Bifidobacterium. Phylogenetic analysis of its 16S rRNA gene sequence revealed that strain GG01(T) formed a single monophyletic cluster and had a distinct line of descent. Based on 16S rRNA gene sequence similarity, the type strains of Bifidobacterium catenulatum JCM 1194(T) (98.3%) and Bifidobacterium pseudocatenulatum (98.1%) JCM 1200(T) were the most closely related to this novel strain, although it was clear that they belonged to different species. hsp60 sequences also supported these relationships. The DNA G+C content of this novel strain was 60.1 mol%. Bifidobacterium moukalabense sp. nov. (type strain GG01(T) = JCM 18751(T) = DSM 27321(T)) is proposed.


Some catecholamine inhibitors do not cause accumulation of nuclear estrogen receptors in rat hypothalamus and anterior pituitary gland.
We have recently shown that the dopamine-beta-hydroxylase inhibitor, U-14,624, decreases the concentration of cytosol estrogen receptors in the mediobasal hypothalamus (MBH) and anterior pituitary gland (AP) in ovariectomized rats, but that it also causes cell nuclear accumulation of estrogen receptors. We tried to determine if this is the mechanism by which other catecholaminergic inhibitors decrease the concentration of cytosol estrogen receptors in either the MBH or AP. The previously reported decrease in the concentration of cytosol estrogen receptors in AP by the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine was confirmed. Also, the decrease in the concentration of cytosol estrogen receptors in MBH after treatment with the dopamine-beta-hydroxylase inhibitors, diethyldithiocarbamate and FLA 63 was demonstrated. In no case was an increase in the concentration of nuclear estrogen receptor accumulation detected after treatment with the drugs. Results of assays of norepinephrine and dopamine levels in MBH after the various treatments suggest that, at the dosage used, U-14,624 has a greater effect on norepinephrine and dopamine levels that the other dopamine-beta-hydroxylase inhibitors. The results of these experiments suggest that inhibitors of dopamine-beta-hydroxylase and tyrosine hydroxylase cause decreases in the concentration of cytosol estrogen receptors in either the MBH or AP that are not referable to increased cell nuclear accumulation of estrogen receptors.


End-of-life care in the United States: policy issues and model programs of integrated care.
End-of-life care financing and delivery in the United States is fragmented and uncoordinated, with little integration of acute and long-term care services. To assess policy issues involving end-of-life care, especially involving the hospice benefit, and to analyse model programs of integrated care for people who are dying. The study conducted structured interviews with stakeholders and experts in end-of-life care and with administrators of model programs in the United States, which were nominated by the experts. The two major public insurance programs--Medicare and Medicaid--finance the vast majority of end-of-life care. Both programs offer a hospice benefit, which has several shortcomings, including requiring physicians to make a prognosis of a six month life expectancy and insisting that patients give up curative treatment--two steps which are difficult for doctors and patients to make--and payment levels that may be too low. In addition, quality of care initiatives for nursing homes and hospice sometimes conflict. Four innovative health systems have overcome these barriers to provide palliative services to beneficiaries in their last year of life. Three of these health systems are managed care plans which receive capitated payments. These providers integrate health, long-term and palliative care using an interdisciplinary team approach to management of services. The fourth provider is a hospice that provides palliative services to beneficiaries of all ages, including those who have not elected hospice care. End-of-life care is deficient in the United States. Public payers could use their market power to improve care through a number of strategies.


ATP-dependent H+ -pump activity in inverted vesicles of Methanosarcina mazei Gö1 and characterization of membrane ATPase.
ATP-dependent H+ -pump activity was found in inverted vesicles of Methanosarcina mazei Gö1 by using acridine orange as a fluorescent probe. The H+ -pump activity specifically required both Mg and sulfite ions, but azide, an inhibitor of F0F1-ATPase, did not inhibit the activity. The membranes prepared from M. mazei also had an Mg-ATPase activity, and at least the presence of vacuolar-type ATPase was detected.


Influences of monocular image degradation on the monocular components of fixation disparity.
The monocular components of the forced vergence fixation disparity curve were evaluated for equal retinal images and for two kinds of monocular retinal image degradation. Computer-generated nonius lines were used to measure the fixation disparity curve components. Monocular defocus was obtained by placing convex lenses before one eye. In the second instance monocular image degradation was achieved by placing light-scattering filters before one eye. A small percentage of subjects displayed unequal distribution of the monocular components of fixation disparity with no image degradation. For both conditions of monocular image degradation, the distribution of the monocular components was found to be biased in favor of the clear image. However, defocus, which affects the high spatial frequencies relatively more than scatter, was found to have a greater effect on the distribution of the monocular components of fixation disparity than scatter.


Trophectoderm differentiation to invasive syncytiotrophoblast is promoted by endometrial epithelial cells during human embryo implantation.
How does the human embryo breach the endometrial epithelium at implantation? Embryo attachment to the endometrial epithelium promotes the formation of multinuclear syncytiotrophoblast from trophectoderm, which goes on to breach the epithelial layer. A significant proportion of natural conceptions and assisted reproduction treatments fail due to unsuccessful implantation. The trophectoderm lineage of the embryo attaches to the endometrial epithelium before breaching this barrier to implant into the endometrium. Trophectoderm-derived syncytiotrophoblast has been observed in recent in vitro cultures of peri-implantation embryos, and historical histology has shown invasive syncytiotrophoblast in embryos that have invaded beyond the epithelium, but the cell type mediating invasion of the epithelial layer at implantation is unknown. Fresh and frozen human blastocyst-stage embryos (n = 46) or human trophoblast stem cell (TSC) spheroids were co-cultured with confluent monolayers of the Ishikawa endometrial epithelial cell line to model the epithelial phase of implantation in vitro. Systems biology approaches with published transcriptomic datasets were used to model the epithelial phase of implantation in silico. Human embryos surplus to treatment requirements were consented for research. Day 6 blastocysts were co-cultured with Ishikawa cell layers until Day 8, and human TSC spheroids modelling blastocyst trophectoderm were co-cultured with Ishikawa cell layers for 48 h. Embryo and TSC morphology was assessed by immunofluorescence microscopy, and TSC differentiation by real-time quantitative PCR (RT-qPCR) and ELISA. Single-cell human blastocyst transcriptomes, and bulk transcriptomes of TSC and primary human endometrial epithelium were used to model the trophectoderm-epithelium interaction in silico. Hypernetworks, pathway analysis, random forest machine learning and RNA velocity were employed to identify gene networks associated with implantation. The majority of embryos co-cultured with Ishikawa cell layers from Day 6 to 8 breached the epithelial layer (37/46), and syncytiotrophoblast was seen in all of these. Syncytiotrophoblast was observed at the embryo-epithelium interface before breaching, and syncytiotrophoblast mediated all pioneering breaching events observed (7/7 events). Multiple independent syncytiotrophoblast regions were seen in 26/46 embryos, suggesting derivation from different regions of trophectoderm. Human TSC spheroids co-cultured with Ishikawa layers also exhibited syncytiotrophoblast formation upon invasion into the epithelium. RT-qPCR comparison of TSC spheroids in isolated culture and co-culture demonstrated epithelium-induced upregulation of syncytiotrophoblast genes CGB (P = 0.03) and SDC1 (P = 0.008), and ELISA revealed the induction of hCGβ secretion (P = 0.03). Secretory-phase primary endometrial epithelium surface transcriptomes were used to identify trophectoderm surface binding partners to model the embryo-epithelium interface. Hypernetwork analysis established a group of 25 epithelium-interacting trophectoderm genes that were highly connected to the rest of the trophectoderm transcriptome, and epithelium-coupled gene networks in cells of the polar region of the trophectoderm exhibited greater connectivity (P < 0.001) and more organized connections (P < 0.0001) than those in the mural region. Pathway analysis revealed a striking similarity with syncytiotrophoblast differentiation, as 4/6 most highly activated pathways upon TSC-syncytiotrophoblast differentiation (false discovery rate (FDR < 0.026)) were represented in the most enriched pathways of epithelium-coupled gene networks in both polar and mural trophectoderm (FDR < 0.001). Random forest machine learning also showed that 80% of the endometrial epithelium-interacting trophectoderm genes identified in the hypernetwork could be quantified as classifiers of TSC-syncytiotrophoblast differentiation. This multi-model approach suggests that invasive syncytiotrophoblast formation from both polar and mural trophectoderm is promoted by attachment to the endometrial epithelium to enable embryonic invasion. No omics datasets were generated in this study, and those used from previously published studies are cited. In vitro and in silico models may not recapitulate the dynamic embryo-endometrial interactions that occur in vivo. The influence of other cellular compartments in the endometrium, including decidual stromal cells and leukocytes, was not represented in these models. Understanding the mechanism of human embryo breaching of the epithelium and the gene networks involved is crucial to improve implantation success rates after assisted reproduction. Moreover, early trophoblast lineages arising at the epithelial phase of implantation form the blueprint for the placenta and thus underpin foetal growth trajectories, pregnancy health and offspring health. This work was funded by grants from Wellbeing of Women, Diabetes UK, the NIHR Local Comprehensive Research Network and Manchester Clinical Research Facility, and the Department of Health Scientist Practitioner Training Scheme. None of the authors has any conflict of interest to declare.


C6 mediates chronic progression of tubulointerstitial damage in rats with remnant kidneys.
Although it was once considered only a marker of glomerular damage, accumulating evidence indicates that proteinuria per se is nephrotoxic and contributes to the progression of renal injury. Several studies have demonstrated that activation of complement in proteinuric urine results in tubular and interstitial damage. It was previously demonstrated that acute complement-mediated interstitial disease is induced by C5b-9. Here the role of C5b-9 in the progression of chronic proteinuric renal disease was investigated in a nonimmunologic remnant kidney model. Five-sixths nephrectomies were performed for normocomplementemic control and C6-deficient PVG rats. Tubulointerstitial injury was assessed by measurement of two independent markers of tubular injury (i.e., vimentin and osteopontin), interstitial accumulation of the extracellular matrix components collagen type I, collagen type IV, and laminin, interstitial macrophage infiltration, and renal function. The two groups developed similar levels of proteinuria and BP. Whereas C3 deposition on the brush border was equivalent for rats in the two groups, C5b-9 deposition was observed only for normocomplementemic rats. At day 35, the degrees of both tubulointerstitial injury and renal failure were the same for the two groups. Tubulointerstitial injury in normocomplementemic rats was still severe at day 70. In contrast, interstitial injury in C6-deficient rats had improved markedly at day 70, with improvements in renal function. In a rat model of chronic progressive renal disease secondary to nephron loss, the initial interstitial changes are complement-independent and largely reversible, whereas progressive interstitial fibrosis is mediated predominantly by C5b-9. Treatment to reduce C5b-9 attack in tubular cells may slow progression and facilitate recovery.


Self-medication against COVID-19 in health workers in Conakry, Guinea.
Data regarding the prevalence and consequences of self-medication during the COVID-19 pandemic in Africa are very limited. The study aimed to explore the frequency and risk factors of self-medication against COVID-19 by health personnel in this study. This cross-sectional study took place in June 2021, in Conakry, in the all three national hospitals and the six community medical centers, and five primary health centers. A multivariate logistic regression model was performed to identify factors associated with self-medication. A total of 975 health workers with a median age of 31 (IQR: 27-40) years, with 504 (51.7%) women were included. The majority were clinicians: physicians (33.1%) or nurses (33.1%). Of all, 46.2% reported having had at least one COVID-19 symptom during the 12 months preceding the survey. The proportion of self-medication was 15.3% among national hospital staff, 12.20% in municipality medical centers and 22.6% in primary health centers (p=0.06). More than two-thirds (68.7%) who selfmedicated did not have a test for SARSCoV- 2 infection. They took antibiotics including azithromycin, amoxicillin, ampicillin (42.2%), acetaminophen (37.4%), vitamin C (27.9%), hydroxychloroquine (23.8%) and medicinal plants (13.6%). The median duration of self-medication was 4 days. Fatigue or asthenia, sore throat, loss of smell and sore throat of a close person were independently associated with selfmedication. Health care workers largely practiced self-medication during the Covid pandemic and without diagnostic testing. The results suggest the need for training and sensitization of medical personnel to avoid the consequences of the molecules used, including hepatotoxicity and antibiotic resistance.


Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog.
The role of cortisol in directing the metabolic response to a combined infusion of glucagon, epinephrine, norepinephrine, and cortisol (stress hormones) was investigated. Chronically catheterized, conscious fasted dogs were studied before hormone infusion and after a 70-hour stress hormone infusion containing glucagon, epinephrine, norepinephrine, and cortisol (n = 11) or containing all these hormones except cortisol (n = 5). Combined stress hormone infusion increased arterial plasma glucagon, cortisol, epinephrine, and norepinephrine approximately sixfold. Whole-body glucose production (Ra), glycogenolysis, and gluconeogenesis were assessed using tracer and arteriovenous-difference techniques. The absence of an increase in cortisol during stress hormone infusion attenuated the increase in arterial plasma glucose concentration and Ra (delta 81 +/- 16 v 24 +/- 3 mg/dL and 1.7 +/- 0.3 v 0.8 +/- 0.4 mg/ kg/min, respectively). However, it did not alter the increase in net hepatic glucose output (delta 0.7 +/- 0.3 v 0.8 +/- 0.4 mg/kg/min). When the increase in cortisol was absent, the increase in net hepatic gluconeogenic precursor uptake was attenuated (delta 0.7 +/- 0.3 v 0.1 +/- 0.3 mg glucose/kg/min) due to a decrease in gluconeogenic precursor levels. The efficiency of gluconeogenesis increased to a greater extent (delta 0.19 +/- 0.07 v 0.31 +/- 0.11) when cortisol was not infused. The absence of an increase in cortisol also led to marked glycogen depletion in the liver (10 +/- 4 v 55 +/- 10 mg/g liver). Cortisol thus plays a pivotal role in the metabolic response to stress hormone infusion by sustaining gluconeogenesis through a stimulatory effect on hepatic gluconeogenic precursor supply and by maintaining hepatic glycogen availability.


Universal (switchable) RAFT agents.
The polymerization of most monomers that are polymerizable by radical polymerization can be controlled by the reversible addition-fragmentation chain transfer (RAFT) process. However, it is usually required that the RAFT agent be selected according to the types of monomer being polymerized. Thus, RAFT agents (dithioesters, trithiocarbonates) suitable for controlling polymerization of "more activated" monomers (MAMs; e.g., styrene, acrylates, methacrylates, etc.) tend to inhibit polymerization of "less activated" monomers (LAMs; e.g., vinyl acetate, N-vinylpyrrolidone, etc.). Similarly RAFT agents suitable for polymerizations of LAMs (xanthates, certain dithiocarbamates) tend to give little or poor control over polymerizations of MAMs. We now report a new class of "switchable" RAFT agents, N-(4-pyridinyl)-N-methyldithiocarbamates, that provide excellent control over polymerization of LAMs and, after addition of 1 equiv of a protic or Lewis acid, become effective in controlling polymerization of MAMs, allowing the synthesis of poly(MAM)-block-poly(LAM) with narrow molecular weight distributions.


AAA repair: sociodemographic disparities in management and outcomes.
To evaluate sociodemographic influences on utilization and outcomes of endovascular abdominal aortic repair (EVAR) for the treatment of abdominal aortic aneurysm (AAA). Secondary data analysis of the State Inpatient Databases for New Jersey. Between 2001 and 2006, a total of 6227 adult subjects (mean [SD] age, 73.3 [8.3] years; 77.6% male) underwent AAA repair (3167 EVAR and 3060 open surgery [OS]). Patients receiving EVAR were older than those undergoing OS (mean [SD] age, 74.2 [8.0] vs 72.4 [8.6] years) (P < .001). Men were 1.60 (95% confidence interval [CI], 1.39-1.77) times more likely to receive EVAR than women. White subjects had the same odds of undergoing EVAR as black subjects, and white subjects had 1.60 (95% CI, 1.29-2.06) times higher odds of receiving EVAR than Hispanics. Subjects with Medicare coverage were 3.90 (96% CI, 2.28-6.59) times more likely to receive EVAR than uninsured subjects. Logistic regression analysis demonstrated that older age, male sex, and Medicare coverage were significantly associated with increased utilization of EVAR and that uninsured subjects and Hispanics are less likely to receive EVAR. Octogenarians and black subjects (odds ratios: 3.69 CI: 2.31-5.91, and 2.59 CI: 1.47-4.54 respectively) had significantly greater likelihood of death after elective AAA repair. For AAA repair, significant sociodemographic disparities exist in the use of endovascular technology and in mortality. The risk of death after elective AAA repair was significantly greater for black subjects. Further analysis is warranted to delineate inequalities of vascular care for AAA and to assist in formulating policy to address these disparities.


Mode-specific tunneling using the Qim path: theory and an application to full-dimensional malonaldehyde.
We present a theory of mode-specific tunneling that makes use of the general tunneling path along the imaginary-frequency normal mode of the saddle point, Qim, and the associated relaxed potential, V(Qim) [Y. Wang and J. M. Bowman, J. Chem. Phys. 129, 121103 (2008)]. The novel aspect of the theory is the projection of the normal modes of a minimum onto the Qim path and the determination of turning points on V(Qim). From that projection, the change in tunneling upon mode excitation can be calculated. If the projection is zero, no enhancement of tunneling is predicted. In that case vibrationally adiabatic (VA) theory could apply. However, if the projection is large then VA theory is not applicable. The approach is applied to mode-specific tunneling in full-dimensional malonaldehyde, using an accurate full-dimensional potential energy surface. Results are in semi-quantitative agreement with experiment for modes that show large enhancement of the tunneling, relative to the ground state tunneling splitting. For the six out-of-plane modes, which have zero projection on the planar Qim path, VA theory does apply, and results from that theory agree qualitatively and even semi-quantitatively with experiment. We also verify the failure of simple VA theory for modes that show large enhancement of tunneling.


Preparation and characterization of composites that contain small carbon nano-onions and conducting polyaniline.
Small multilayer fullerenes, also known as carbon nano-onions (CNOs; 5-6 nm in diameter, 6-8 shells), show higher reactivity than other larger carbon nanostructures. Here we report the first example of an in situ polymerization of aniline on phenyleneamine-terminated CNO surfaces. The green, protonated, conducting emeraldine polyaniline (PANI) was directly synthesized on the surface of the CNO. The functionalized and soluble CNO/PANI composites were characterized by TEM, SEM, DSC, Raman, and infrared spectroscopy. The electrochemical properties of the conducting CNO/PANI films were also investigated. In comparison with pristine CNOs, functionalized carbon nanostructures show dramatically improved solubility in protic solvents, thus enabling their easy processing for coatings, nanocomposites, and biomedical applications.


Comparison of the Physical Characteristics and Behavior in ABC Transporter A1, A7 or Apolipoprotein E Knockout Mice with Lipid Transport Dysfunction.
The physical characteristics and behavior of the ATP-binding cassette (ABC) A1, A7, and apolipoprotein (apo) E knockout (KO) mice with lipid transport dysfunction were investigated. These KO mice exhibited adequate growth, and their body masses increased steadily. No remarkable changes were observed in their blood pressure and heart rate. However, there was a slight increase in the heart rate of the ABCA7 KO mice compared with that of the wild-type (WT) mice. ABCA1 and apoE KO mice showed hypo- and hyper-cholesterol concentrations in the plasma, respectively. With regard to the cerebrum, however, the weight of the ABCA1 KO mice was lighter than those of the other genotypes. Furthermore, the cholesterol, triglyceride and phospholipid concentrations, and fatty acid composition were generally similar. Compared with the WT mice, ABCA1 KO mice stayed for a shorter time in the closed arm of the elevated plus maze, and performed worse in the initial stage of the Morris water maze. To thermal stimuli, the ABCA1 and apoE KO mice showed hyper- and hypo-sensitivities, respectively. Only the response of the ABCA1 KO mice was significantly inhibited by pretreatment with indomethacin. A low concentration of the prostaglandin E metabolites was detected in the plasma of the ABCA1 KO mice. Thus, ABCA1 is thought to play a specific role in the neural function.


Effects of Thai black sticky rice extract on oxidative stress and lipid metabolism gene expression in HepG2 cells.
Anthocyanins, which are found in some food, including Thai black sticky rice, are reported to have health-promoting properties. Oxidative stress plays a major role in the pathogenesis of many degenerative diseases induced by free radicals, such as cardiovascular disease, stroke and cancer. We evaluated the anthocyanin-rich extract (ARE) from Thai black sticky rice for antioxidative and antihyperlipidemic effects on HepG2 cells. Cell viability was investigated with the neutral red assay and the MTT assay, and oxidative stress was determined by the DCFH-DA assay. RT-PCR was used to evaluate the effect of ARE on LDLR, HMG-CoAR, PPAR (α1,γ) and LXRa gene expression. We found that ARE at high doses (≥ 800 mg/L) induces cytotoxicity. However, at 600-1000 mg/L it reduced intracellular oxidative stress (P < 0.05) in a dose-dependent manner, and at 200 mg/L it significantly enhanced the expression of the LDLR gene in HepG2 cells. We concluded that ARE can be beneficial for health promotion by reducing oxidative stress and enhancing LDL clearance, regulating LDLR production on the cell surface membrane, thereby maintaining lipid homeostasis.


Cost-effectiveness analysis on elderly pneumococcal vaccination in the Netherlands: Challenging the Dutch Health Council's advice.
Recently, the Dutch Health Council advised on elderly pneumococcal vaccination favouring the conventional polysaccharide vaccine over the novel conjugated vaccine. This advice was strongly inspired by a cost-effectiveness analysis considered to show favourable outcomes for the polysaccharide but not for the conjugated vaccine. We argue that using the same data and methods as presented by the Health Council, a different perspective on the results leads to a conclusion that not only the polysaccharide but also the conjugated pneumococcal vaccine is cost-effective. Our alternative perspective concerns the use of realistic vaccine prices, and applying an adequate time horizon for cost-effectiveness modelling. Notably, for one-off vaccination of 65-years old elderly, in all investigated analyses, also the conjugated vaccine seems cost-effective; i.e. well below the threshold of €20,000 per quality-adjusted life year, reflecting the most stringent threshold used for vaccines in the Netherlands.


Measurement of magnetostriction coefficients of epitaxial garnet films.
A technique for measuring the magnetostriction coefficients of epitaxial garnet films on 50-mm-diam wafers is described. The measurement is based on the shift of the microwave ferrimagnetic resonance produced by stressing the film, which is achieved by supporting the wafer around its circumference and reducing the atmospheric pressure on one side. A simple, nonresonant transmission microwave spectrometer which is well suited for measurements on large wafers is also described.