Reinforcing or challenging the status quo: A grounded theory of how the model minority myth shapes Asian American activism.
Compared to other People of Color in the United States, Asian Americans are often seen as uninterested in activism. Furthermore, the widespread model minority myth (MMM) perpetuates the monolithic image of Asian Americans as successful in society and thus unaffected by racial oppression and uninterested in activism. Despite others' perceptions, Asian American college students have historically engaged in activist efforts and worked to reject the stereotypical views of their racial group as apolitical under the MMM. However, much remains to be learned about the consequences of the MMM on Asian American college students' perceptions and engagement in activism, and how such individuals make sense of the MMM and activism through interacting with their ecological contexts. Thus, the present study addresses this gap in the literature and is guided by the question: How do Asian American college students' perspectives and engagement in activism develop and operate in relation to the MMM? Using a constructivist grounded theory analytic approach, 25 Asian American college students participated in semistructured interviews, and our findings developed a grounded theory of how Asian American college students are embedded within micro- and macrolevel environments (e.g., familial, cultural, and societal contexts) that uphold the MMM and further shape how they make sense of and engage in activism. Results further revealed the consequences of the MMM as a legitimizing ideology on Asian American students' attitudes toward and involvement in challenging and/or reinforcing the status quo. Implications for future research and practice supporting Asian American activism and the broader pursuit for social justice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


A two crystal arrangement to fight efficiency saturation in cross-polarized wave generation.
We describe a method that overcomes the observed saturation effect in cross polarized wave (XPW) generation. The previously reported internal efficiencies for XPW generation are known to be limited to around 15% whatever the length of the nonlinear medium and/or the input intensity values are. At the opposite, the theoretical limit had been estimated to be close to 25%. Here we show that using two thin BaF(2) crystals separated at optimum distance the saturation level of XPW generation efficiency can be drastically increased. An internal efficiency of 30% is demonstrated experimentally using two BaF(2) crystals.


Specific Th1 cytokine down-regulation associated with primary clinically derived human immunodeficiency virus type 1 Nef gene-induced expression.
HIV-1 infection is associated with a progressive and functional decline in the CD4+ lymphoid Th1 subset. Here, we propose that the HIV nef gene product may function as a specific regulator of Th1 cytokine production. By use of a T cell-specific inducible expression system, we show that upon T cell activation, induced nef expression down-regulated both IL-2 and IFN-gamma production in a dose-dependent manner, whereas IL-4, IL-9, IL-13, IL-8, and TNF-alpha production remained unaffected. In addition to this, independent transfected clones expressing various nef genes, including nef sequences amplified directly from an HIV-1 primary clinical isolate, displayed a similar pattern of cytokine expression. The specific Th1 impairment induced by nef, therefore, seems to be an important and conserved feature of HIV-1 infection and may represent a significant function of this viral gene in AIDS pathogenesis.


Comparative biodegradation analysis of three compostable polyesters by a marine microbial community.
Biodegradable plastics can be used in applications where the end product cannot be efficiently recycled due to high levels of contaminations, e.g., food or soil. Some of these plastics have a dedicated end of life, such as composting, but their degradation in the marine environment is poorly understood. In this study we showed that marine microbial communities can degrade a range of biodegradable polymers with different physical and chemical properties and use these as a sole carbon source for growth. We have also provided insights into the degradation mechanisms using a combined metagenomic and metaproteomic approach. In addition, we have identified three new enzymes that are capable of degrading both aliphatic polymers and aliphatic-aromatic copolymers, which can be used for biotechnological applications.


Combined OX40L and mTOR blockade controls effector T cell activation while preserving Treg reconstitution after transplant.
A critical question facing the field of transplantation is how to control effector T cell (Teff) activation while preserving regulatory T cell (Treg) function. Standard calcineurin inhibitor-based strategies can partially control Teffs, but breakthrough activation still occurs, and these agents are antagonistic to Treg function. Conversely, mechanistic target of rapamycin (mTOR) inhibition with sirolimus is more Treg-compatible but is inadequate to fully control Teff activation. In contrast, blockade of OX40L signaling has the capacity to partially control Teff activation despite maintaining Treg function. We used the nonhuman primate graft-versus-host disease (GVHD) model to probe the efficacy of combinatorial immunomodulation with sirolimus and the OX40L-blocking antibody KY1005. Our results demonstrate significant biologic activity of KY1005 alone (prolonging median GVHD-free survival from 8 to 19.5 days), as well as marked, synergistic control of GVHD with KY1005 + sirolimus (median survival time, >100 days; P < 0.01 compared to all other regimens), which was associated with potent control of both TH/TC1 (T helper cell 1/cytotoxic T cell 1) and TH/TC17 activation. Combined administration also maintained Treg reconstitution [resulting in an enhanced Treg/Teff ratio (40% over baseline) in the KY1005/sirolimus cohort compared to a 2.9-fold decrease in the unprophylaxed GVHD cohort]. This unique immunologic signature resulted in transplant recipients that were able to control GVHD for the length of analysis and to down-regulate donor/recipient alloreactivity despite maintaining anti-third-party responses. These data indicate that combined OX40L blockade and sirolimus represents a promising strategy to induce immune balance after transplant and is an important candidate regimen for clinical translation.


Morphological alterations in newly born dentate gyrus granule cells that emerge after status epilepticus contribute to make them less excitable.
Computer simulations of external current stimulations of dentate gyrus granule cells of rats with Status Epilepticus induced by pilocarpine and control rats were used to evaluate whether morphological differences alone between these cells have an impact on their electrophysiological behavior. The cell models were constructed using morphological information from tridimensional reconstructions with Neurolucida software. To evaluate the effect of morphology differences alone, ion channel conductances, densities and distributions over the dendritic trees of dentate gyrus granule cells were the same for all models. External simulated currents were injected in randomly chosen dendrites belonging to one of three different areas of dentate gyrus granule cell molecular layer: inner molecular layer, medial molecular layer and outer molecular layer. Somatic membrane potentials were recorded to determine firing frequencies and inter-spike intervals. The results show that morphologically altered granule cells from pilocarpine-induced epileptic rats are less excitable than control cells, especially when they are stimulated in the inner molecular layer, which is the target area for mossy fibers that sprout after pilocarpine-induced cell degeneration. This suggests that morphological alterations may act as a protective mechanism to allow dentate gyrus granule cells to cope with the increase of stimulation caused by mossy fiber sprouting.


Self-perceived problems in daily activities and strategy building in people with different stages of dementia.
People with dementia experience severe problems in their daily lives. However, little is known about self-perceived problems in the course of dementia. The aim of our study was to assess self-perceived problems with daily activities as well as individually developed strategies of older people of different cognitive status. Semi-structured interviews were conducted with 25 participants (mean age 67.6 years, 56% female, 24% healthy, 28% mild dementia, 48% severe dementia). Questions addressed problems in daily activities, their occurrence and the behaviour toward them, and their developed strategies. Information was summarized quantitatively and evaluated using the chi-squared and Kruskal-Wallis tests. Self-perceived problems included awareness of physical and cognitive deficits in managing daily life, disturbing factors, and lost autonomy. Increased cognitive impairment was associated with more problems in daily life, even though people with severe dementia seemed not to recognize them. The most frequently reported strategies included orderliness, doing things immediately, and the use of external aids. While healthy people and those with mild dementia developed strategies, those with severe dementia reported only few strategies. Our findings indicate that self-perceived problems in daily life and strategy development are strongest in mild dementia, while people with more severe dementia tend to perceive no problems at all while correctly reflecting their current state of dependency. Importantly, despite memory loss during early stages of dementia, strategies are still being developed. Accordingly, strategies for daily living should be taught in early dementia to sustain an independent lifestyle.


Automated measurement of latent morphological features in the human corpus callosum.
Our objective was to develop a novel factor-based analysis of the morphology of the corpus callosum and assess its applicability to the study of normal development, intelligence, and other subject characteristics. The contour of the corpus callosum was defined in the midsagittal planes of the MRI scans of 325 subjects, 6 to 88 years of age. The contours were coregistered, rescaled, and resampled to 50 points that were then entered into a principal components analysis with varimax rotation. The analysis yielded 8 factors for the contours of 138 healthy subjects. A second analysis of contours from 187 subjects in a patient group extracted 8 similar factors. Correlations of factor scores with conventional measures of callosum shape supported the construct validity of the assignment of morphological features to each of the factors. Correlations of factor scores with age, sex, handedness, ventricular volume, and IQ demonstrated the predictive validity of the factor structure and helped to define the neural correlates of these subject characteristics. We conclude that factor-based measures capture latent morphological features of the corpus callosum that are reliable and valid. Future studies will determine whether these novel measures are more closely related to neurobiologically important features of the corpus than are conventional measures of callosum size and shape.


Teaching mechanical ventilation.
Participants have stated that having actually experienced the modes of the ventilator and the components of weaning parameters, they are better able to understand and manage ventilated patients, as opposed to trying to memorize them as in the past. They also have a much greater appreciation for the discomfort experienced by the ventilated patient. (Most students cannot tolerate a PEEP of 10 centimeters of H2O for more than a few minutes). Many remarked that they are much more tolerant with their agitated, intubated patients because they can now understand their agitation. The session has proved to be an effective teaching tool. It is cost effective, does not take long and is enthusiastically received by the participants who believe they have gained a better understanding of how to properly care for their anxious, intubated patients.


On Enrichment Strategies for Biomarker Stratified Clinical Trials.
In the era of precision medicine, drugs are increasingly developed to target subgroups of patients with certain biomarkers. In large all-comer trials using a biomarker stratified design, the cost of treating and following patients for clinical outcomes may be prohibitive. With a fixed number of randomized patients, the efficiency of testing certain treatments parameters, including the treatment effect among biomarker-positive patients and the interaction between treatment and biomarker, can be improved by increasing the proportion of biomarker positives on study, especially when the prevalence rate of biomarker positives is low in the underlying patient population. When the cost of assessing the true biomarker is prohibitive, one can further improve the study efficiency by oversampling biomarker positives with a cheaper auxiliary variable or a surrogate biomarker that correlates with the true biomarker. To improve efficiency and reduce cost, we can adopt an enrichment strategy for both scenarios by concentrating on testing and treating patient subgroups that contain more information about specific treatment parameters of primary interest to the investigators. In the first scenario, an enriched biomarker stratified design enriches the cohort of randomized patients by directly oversampling the relevant patients with the true biomarker, while in the second scenario, an auxiliary-variable-enriched biomarker stratified design enriches the randomized cohort based on an inexpensive auxiliary variable, thereby avoiding testing the true biomarker on all screened patients and reducing treatment waiting time. For both designs, we discuss how to choose the optimal enrichment proportion when testing a single hypothesis or two hypotheses simultaneously. At a requisite power, we compare the two new designs with the BSD design in terms of the number of randomized patients and the cost of trial under scenarios mimicking real biomarker stratified trials. The new designs are illustrated with hypothetical examples for designing biomarker-driven cancer trials.


Plasma glucose within the normal range is not associated with carotid atherosclerosis: prospective results in subjects with normal glucose tolerance from the Bruneck Study.
There is substantial evidence that glucose intolerance is associated with an increased risk of cardiovascular disease. However, it is not well established whether plasma glucose is independently related to atherosclerosis when glucose tolerance is normal and, if so, to which stage of the complex atherosclerotic process. We prospectively examined the status of carotid arteries in 625 subjects aged 40-79 years who were randomly selected from the general population and had normal glucose tolerance (according to World Health Organization criteria) both at baseline and at 5 years of follow-up. All subjects had high-resolution echo-duplex evaluation of the common and internal carotid arteries (eight regions of interest on both sides) in 1990 and 1995 to detect the change in carotid status over time. The occurrence of new plaques in previously normal segments was termed "incident nonstenotic" or "early atherosclerosis," and the occurrence of stenosis in >40% of previously normal segments was termed "incident stenotic" or "advanced atherosclerosis." In addition, we evaluated the changes in the atherosclerosis score (the sum of all plaques) during the follow-up, and we measured intimal-medial thickening (IMT) in the common carotid artery in 1995. In all subjects, several candidate risk factors were assessed: sex, age, BMI, waist-to-hip ratio, glucose, HbA1c, insulin, urate, lipids, apolipoproteins A1 and B, blood pressure, lipoprotein(a), fibrinogen, antithrombin III, factor V Leiden mutation, ferritin, leukocyte count, smoking, alcohol intake, physical activity, and socioeconomic status. Fasting plasma glucose (FPG), plasma glucose 2 hr after the glucose load (2-h PG), and HbA1c concentrations in 1990 and 1995 were averaged in each subject to obtain an estimate of long-term glucose exposure of the arterial wall. Linear or logistical regression analyses indicated that neither baseline glucose and HbA1c levels nor mean FPG, mean 2-h PG, or mean HbA1c in 1990 and 1995 were independently related to IMT, a 5-year change in the atherosclerotic score, incident nonstenotic (early) atherosclerosis, or incident stenotic (advanced) atherosclerosis. Likewise, subjects with FPG levels above the median and subjects in the new category of "impaired fasting glucose" did not have an increased occurrence or progression of atherosclerosis. All results were consistent before and after adjustment for other vascular risk factors and possible confounders. These results suggest that plasma glucose levels within the normal range (<7.8 mg/dl both at FPG and 2-h PG) are not independently related to any stage of atherosclerosis.


From shelf to shelf: assessing historical and contemporary genetic differentiation and connectivity across the Gulf of Mexico in Gag, Mycteroperca microlepis.
Describing patterns of connectivity among populations of species with widespread distributions is particularly important in understanding the ecology and evolution of marine species. In this study, we examined patterns of population differentiation, migration, and historical population dynamics using microsatellite and mitochondrial loci to test whether populations of the epinephelid fish, Gag, Mycteroperca microlepis, an important fishery species, are genetically connected across the Gulf of Mexico and if so, whether that connectivity is attributable to either contemporary or historical processes. Populations of Gag on the Campeche Bank and the West Florida Shelf show significant, but low magnitude, differentiation. Time since divergence/expansion estimates associated with historical population dynamics indicate that any population or spatial expansions indicated by population genetics would have likely occurred in the late Pleistocene. Using coalescent-based approaches, we find that the best model for explaining observed spatial patterns of contemporary genetic variation is one of asymmetric gene flow, with movement from Campeche Bank to the West Florida Shelf. Both estimated migration rates and ecological data support the hypothesis that Gag populations throughout the Gulf of Mexico are connected via present day larval dispersal. Demonstrating this greatly expanded scale of connectivity for Gag highlights the influence of "ghost" populations (sensu Beerli) on genetic patterns and presents a critical consideration for both fisheries management and conservation of this and other species with similar genetic patterns.


The Italian reference sites of the European innovation partnership on active and healthy ageing: Progetto Mattone Internazionale as an enabling factor.
Ageing population implies an increasing demand for health care services and resources, unsustainable according to current previsions. The European Commission is tackling this challenge throughout initiatives such as the European Innovation Partnership on Active and Healthy Ageing (EIP-AHA), where all the efforts are aligned to the common goal of adding two active and healthy years to the life of European Union (EU) citizens. We presented the collaborative efforts of Italian Reference Site Collaborative Network 2012-2015. Italian regions joined forces through the "Progetto Mattone Internazionale" of the Ministry of Health developing several national and international collaborations. Activities from all five Italian reference sites are presented with different good practices and scale-up approaches for improving health in ageing population. The simultaneous development of these activities allowed the strengthening of the coordination of Italian stakeholders in the European arena fostering collaboration and supporting the streamlining of the Italian regions still outside these projects.


Protein visualization and manipulation in Drosophila through the use of epitope tags recognized by nanobodies.
Expansion of the available repertoire of reagents for visualization and manipulation of proteins will help understand their function. Short epitope tags linked to proteins of interest and recognized by existing binders such as nanobodies facilitate protein studies by obviating the need to isolate new antibodies directed against them. Nanobodies have several advantages over conventional antibodies, as they can be expressed and used as tools for visualization and manipulation of proteins in vivo. Here, we characterize two short (<15aa) NanoTag epitopes, 127D01 and VHH05, and their corresponding high-affinity nanobodies. We demonstrate their use in Drosophila for in vivo protein detection and re-localization, direct and indirect immunofluorescence, immunoblotting, and immunoprecipitation. We further show that CRISPR-mediated gene targeting provides a straightforward approach to tagging endogenous proteins with the NanoTags. Single copies of the NanoTags, regardless of their location, suffice for detection. This versatile and validated toolbox of tags and nanobodies will serve as a resource for a wide array of applications, including functional studies in Drosophila and beyond.


Peritoneal keratin granulomas with carcinomas of endometrium and ovary and atypical polypoid adenomyoma of endometrium. A clinicopathological analysis of 22 cases.
Twenty-two cases of keratin granulomas of the peritoneum associated with endometrioid adenocarcinoma with squamous differentiation of the endometrium, the ovary, or both, and with an atypical polypoid adenomyoma of the endometrium were reviewed. Follow-up data were available in 18 cases. Twelve patients were well and disease free 13 months to 15.2 years postoperatively; one patient died of unrelated disease 21 years postoperatively; three patients were tumor free with a short duration of follow-up; one patient, who had a stage Ic ovarian tumor, died of pulmonary embolism during the treatment of recurrent tumor 1 year after operation; and a final patient, who had been followed for 3 months after operation for stage IV disease, was alive with residual tumor. At least six patients with stage I carcinomas were treated with postoperative irradiation because the granulomas had raised a suspicion of advanced disease. Follow-up data on the patients in this series suggest that peritoneal keratin granulomas have no prognostic significance and should be distinguished from viable tumor implants on microscopic examination.


Evidence-based dental care--a concept review.
Evidence-based (science-based) care is the prevailing paradigm in the health sciences. This paper briefly reviews the basic concepts of evidence-based care. Assessment of scientific evidence including information retrieval, evaluation of the quality of evidence, and finally the synthesis of collected evidence is described. Practitioner approach to evidence-based care through the twin modalities of literature reviews and clinical practice guidelines is outlined. It is concluded that the promotion of outcomes research and the adoption of evidence-based practice is likely to improve the delivery of a high standard of quality dental care.


Endocrine and AhR-CYP1A pathway responses to the water-soluble fraction of oil in zebrafish (Danio rerio Hamilton).
Crude oil is a complex mixture of compounds of which the water-soluble fraction (WSF) is considered to be bioavailable and potentially toxic to aquatic biota. Containing numerous compounds, WSF becomes a source of multiple chemical stressors to wildlife when introduced into the environment. To study the combined effects of WSF components on aquatic biota, the model species zebrafish (Danio rerio Hamilton) was exposed for 24 or 72 h to 10 or 50% WSF solution of known composition, generated from artificially weathered North Sea crude oil. Hepatic expression of genes involved in the aryl hydrocarbon receptor-cytochrome P-450 1A (AhR-CYP1A) pathway (AhR2, AhRR1, CYP1A1) and steroidogenesis (StAR, CYP11A, 3β-HSD, CYP19A, CYP19B) was measured, as well as estrogen receptors ERα and ERβ1. Induction of CYP1A and particularly of AhRR1 was observed while ERα and steroidogenic enzymes CYP11A and 3β-HSD were downregulated. Regression analysis demonstrated a negative relationship between AhR-CYP1A pathway and endocrine transcript levels, although causality remains to be established. These findings indicate that exposure to WSF of oil disrupts steroidogenesis and may therefore constitute a potential risk for reproductive ability of aquatic organisms. In addition, it is proposed that hepatic gene expression of AhRR1 may serve as a novel biomarker of WSF exposure.


Basic study of susceptibility-weighted imaging at 1.5T.
With the aim of sequence optimization in susceptibility-weighted imaging (SWI), 2 image acquisition parameters (slice thickness and matrix size) and 2 image processing conditions (number of slices per minimum intensity projection (MIP) and Sliding Window) were investigated using a 1.5-T magnetic resonance imaging (MRI) system. The subjects were 12 healthy volunteers and the target region for scanning was the whole brain. Informed consent was obtained from all subjects. First, susceptibility-weighted images were acquired with various slice thicknesses from 1mm to 5mm and various matrix sizes from 256 x 256 to 512 x 512, and the images were assessed in terms of the contrast-to-noise ratio (CNR) and were also visually evaluated by three radiologists. Then, the number of slices per MIP and the usefulness of the Sliding Window were investigated. In the study of the optimal slice thickness and matrix size, the results of visual evaluation suggested that a slice thickness of 3mm and a matrix size of 448 x 448 are optimal, while the results of evaluation based on CNR were not significant. As regards the image processing conditions, the results suggested that the number of slices per MIP should be set to a minimum value of 2 and that the use of Sliding Window is effective. The present study provides useful reference data for optimizing SWI sequences.


The Chewing Lice (Insecta: Phthiraptera: Ischnocera: Amblycera) of Japanese Pigeons and Doves (Columbiformes), with Descriptions of Three New Species.
The chewing louse fauna of pigeons and doves in Japan is reviewed based on published records and new collections. An updated checklist of the chewing lice of Japanese pigeons and doves is provided, and 3 new species are described: Columbicola asukae n. sp. and Coloceras nakamurai n. sp., both from Columba janthina Temminck, 1830 (Japanese wood pigeon), and Columbicola lemoinei n. sp. from Treron formosae permagnus Stejneger, 1887, and Treron formosae medioximus (Bangs, 1901) (whistling green-pigeons). This checklist includes data on the first records of Coloceras chinense (Kellogg and Chapman, 1902), Coloceras piriformis ( Tendeiro, 1969 ), and Columbicola guimaraesi Tendeiro, 1965, in Japan. New host records of Hohorstiella sp. from Columba janthina and Treron formosae permagnus, and Coloceras sp. from Treron sieboldii sieboldii (Temminck, 1835) (white-bellied green-pigeon) are provided.


HOXD3 Up-regulating KDM5C Promotes Malignant Progression of Diffuse Large B-Cell Lymphoma by Decreasing p53 Expression
Diffuse large B-cell lymphoma is a type of B-cell non-Hodgkin lymphoma with a high incidence. About one-third of patients are resistant or eventually relapse. The prognosis for patients with relapsed/resistant diffuse large B-cell lymphoma who need salvage therapy is not optimistic. To explore whether homebox D3 binding to lysine (K)-specific demethylase 5C promoted malignant progression of diffuse large B-cell lymphoma by decreasing p53 expression. Cell culture study. The mRNA and protein expression of lysine (K)-specific demethylase 5C and homebox D3 in cells were respectively detected by real-time quantitative polymerase chain reaction analysis and Western blot. Real-time quantitative polymerase chain reaction analysis and Western blot were also applied to determine the transfection effects of shRNA-KDM5C or OeHOXD3 in OCI-Ly7 cells. After transfection, the cell viability, proliferation, and apoptosis were respectively analyzed by Cell Counting Kit-8 assay, EdU staining, and acridine orange—ethidium bromide staining. The interaction between homebox D3 and lysine (K)-specific demethylase 5C promoter was verified by the dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay. Lysine (K)-specific demethylase 5C mRNA expression (HBL1 2.84 ± 0.29; SUDHL4 3.53 ± 0.21; OCI-Ly8 4.06 ± 0.24; OCI-Ly7 5.03 ± 0.28 vs. GM12878 1.00 ± 0.07; all P < .001) and protein expression (HBL1 1.52 ± 0.06; SUDHL4 1.77 ± 0.10; OCI-Ly8 2.34 ± 0.07; OCI-Ly7 2.78 ± 0.07 vs. GM12878 1.00 ± 0.07; all P < .001) in DLBCL cells were higher than that in GM12878 cells and showed the highest in OCI-Ly7 cells. Homebox D3 mRNA (OCI-Ly7 3.85 ± 0.17 vs. GM12878 1.00 ± 0.05; P < .001) and protein (OCI-Ly7 1.73 ± 0.10 vs. GM12878 1.00 ± 0.06; P < .001) expression were also highly expressed in OCI-Ly7 cells. Moreover, down-regulation of lysine (K)-specific demethylase 5C suppressed the viability and proliferation and enhanced the apoptosis of OCI-Ly7 cells. Knockdown of lysine (K)-specific demethylase 5C decreased the B-cell lymphoma 2 expression while increased the expression of Bax, cleaved caspase 3, cytochrome C, p53, and p21. The transcription factor homebox D3 was confirmed to interact with the lysine (K)-specific demethylase 5C promoter. Homebox D3 overexpression could reverse the regulating effect of down-regulation of lysine (K)-specific demethylase 5C on the OCI-Ly7 cells. Homebox D3 up-regulating lysine (K)-specific demethylase 5C promotes malignant progression of diffuse large B-cell lymphoma by decreasing p53 expression.


The association of proton movement with galactose transport into subcellular membrane vesicles of Escherichia coli.
1. Subcellular membrane vesicles were prepared from a strain of Escherichia coli constitutive for the GalP galactose-transport system. 2. The addition of substrates of the GalP transport system to vesicle suspensions promoted alkaline pH changes, which provided direct evidence for the coupling of sugar and proton transport. 3. Respiration-energized galactose transport was progressively inhibited at pH values above 6.0, and was abolished by agents that render the membrane permeable to protons. 4. The combined effects of valinomycin, the nigericin-like compound A217 and pH on galactose transport suggested that both delta pH and delta psi components of the protonmotive force contributed to energization of galactose transport. 5. These results substantiate the conclusion that the GalP transport system operates by a chemiosmotic mechanism.


Resetting the dynamic range of hypothalamic-pituitary-adrenal axis stress responses through pregnancy.
The hypothalamic-pituitary-adrenal (HPA) axis plays a key role in the neuroendocrine response to stress. Dynamic changes in HPA axis regulation and hence HPA responsivity occur over the lifetime of an animal. This article focuses on two extremes of the spectrum. The first occurs naturally during pregnancy when stress responses are dampened. The second, at the opposite end of the scale, occurs in offspring of mothers who were exposed to stress during pregnancy and display exaggerated HPA axis stress responses. Reduced glucocorticoid output in response to stress in pregnancy may have important consequences for conserving energy supply to the foetus(es), in modulating immune system adaptations and in protecting against adverse foetal programming by glucocorticoids. Understanding the mechanisms underpinning this adaptation in pregnancy may provide insights for manipulating HPA axis responsiveness in later life, particularly in the context of resetting HPA axis hyperactivity associated with prenatal stress exposure, which may underlie several major pathologies, including cardiovascular disease, diabetes mellitus type 2, obesity, cognitive decline and mood disorders.


Medical Marijuana in the Pediatric Population With Epilepsy-What You Should Know.
This article discusses the controversial but promising topic of medical marijuana (MM) use in the pediatric population with epilepsy. Included is the importance of MM throughout history, the pharmacodynamics and pharmacokinetics, and a literature review that provides anecdotal evidence of the positive effect MM has on children suffering from seizures. From this literature review, dosage for treatment and management is provided. Also discussed is the recent FDA-approved pharmaceutical grade CBD product, Epidiolex, for treatment of two pediatric-onset seizure syndromes, Lennox-Gastaut and Dravet. Clinical implications regarding adverse side effects of MM use are also discussed. The aim of this article is to arm providers with contemporary knowledge on the risks and benefits of MM use in the pediatric population with epilepsy, which may boost their skills and confidence in educating and advocating for children with seizures. This novel, ever-changing medication is in the forefront of history and the news, making this topic especially important for review.


Primary care issues related to the treatment of depression in elderly patients.
Late-life depression is a serious public health problem and a concern for the primary care physician. Illnesses that often occur with aging may present in association with depression, which can interfere with patient compliance and recovery and worsen disease outcomes. Late-life depression is also associated with disproportionately high rates of completed suicide and high mortality rates independent of suicide. A shared therapeutic nihilism exists between many patients and physicians, who inappropriately accept major depression as normal and inevitable during advanced age and with related chronic disease states. Thus, the older depressed patient is too often not diagnosed and not treated. Furthermore, symptom overlap between depression, anxiety, and many chronic medical illnesses may confuse proper diagnosis. Therefore, screening for and diagnosing depression using an inclusive approach is highly recommended in the primary care setting and long-term care facility. Because of their improved safety, tolerability, and ease of dosing, newer generation antidepressants, such as the selective serotonin reuptake inhibitors, should be the first choice of treatment. Collaboration between primary and specialty providers is recommended, and referral to psychiatry is advised for patients with complex medical illnesses, comorbid psychiatric illness, suicidal ideation or intent, complicated medication regimens, and poor or no response to antidepressant therapy.


Nonfilling carbon coating of porous silicon micrometer-sized particles for high-performance lithium battery anodes.
Silicon is widely recognized as one of the most promising anode materials for lithium-ion batteries due to its 10 times higher specific capacity than graphite. Unfortunately, the large volume change of Si materials during their lithiation/delithiation process results in severe pulverization, loss of electrical contact, unstable solid-electrolyte interphase (SEI), and eventual capacity fading. Although there has been tremendous progress to overcome these issues through nanoscale materials design, improved volumetric capacity and reduced cost are still needed for practical application. To address these issues, we design a nonfilling carbon-coated porous silicon microparticle (nC-pSiMP). In this structure, porous silicon microparticles (pSiMPs) consist of many interconnected primary silicon nanoparticles; only the outer surface of the pSiMPs was coated with carbon, leaving the interior pore structures unfilled. Nonfilling carbon coating hinders electrolyte penetration into the nC-pSiMPs, minimizes the electrode-electrolyte contact area, and retains the internal pore space for Si expansion. SEI formation is mostly limited to the outside of the microparticles. As a result, the composite structure demonstrates excellent cycling stability with high reversible specific capacity (∼1500 mAh g(-1), 1000 cycles) at the rate of C/4. The nC-pSiMPs contain accurate void space to accommodate Si expansion while not losing packing density, which allows for a high volumetric capacity (∼1000 mAh cm(-3)). The areal capacity can reach over 3 mAh cm(-2) with the mass loading 2.01 mg cm(-2). Moreover, the production of nC-pSiMP is simple and scalable using a low-cost silicon monoxide microparticle starting material.


Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family.
Low voltage-activated Ca2+ channels play important roles in pacing neuronal firing and producing network oscillations, such as those that occur during sleep and epilepsy. Here we describe the cloning and expression of the third member of the T-type family, alpha1I or CavT.3, from rat brain. Northern analysis indicated that it is predominantly expressed in brain. Expression of the cloned channel in either Xenopus oocytes or stably transfected human embryonic kidney-293 cells revealed novel gating properties. We compared these electrophysiological properties to those of the cloned T-type channels alpha1G and alpha1H and to the high voltage-activated channels formed by alpha1Ebeta3. The alpha1I channels opened after small depolarizations of the membrane similar to alpha1G and alpha1H but at more depolarized potentials. The kinetics of activation and inactivation were dramatically slower, which allows the channel to act as a Ca2+ injector. In oocytes, the kinetics were even slower, suggesting that components of the expression system modulate its gating properties. Steady-state inactivation occurred at higher potentials than any of the other T channels, endowing the channel with a substantial window current. The alpha1I channel could still be classified as T-type by virtue of its criss-crossing kinetics, its slow deactivation (tail current), and its small (11 pS) conductance in 110 mM Ba2+ solutions. Based on its brain distribution and novel gating properties, we suggest that alpha1I plays important roles in determining the electroresponsiveness of neurons, and hence, may be a novel drug target.


Efficacy of anti-suppression therapy in improving binocular vision in children with small-angle Esotropia.
To evaluate the efficacy of anti-suppression exercises in children with small-angle esotropia in achieving binocular vision. A retrospective review of patients aged 3-8 years who underwent anti-suppression exercises for either monocular or alternate suppression between January 2016 and December 2021 was conducted. Patients with esotropia less than 15 prism diopters (PD) and visual acuity ≥ 6/12 were included. Patients with previous intra-ocular surgery or less than three-month follow-up were excluded. Success was defined as the development of binocular single vision (BSV) for distance, near, or both (measured clinically with either the 4 prism base out test or Worth four dot test) and maintained at two consecutive visits. Qualified success was defined as the presence of diplopia response for both distance and near. Additionally, improvement in near stereo acuity was measured using the Stereo Fly test. Eighteen patients with a mean age of 5.4 ± 1.38 years (range 3-8 years) at the time of initiation of exercises were included in the study. The male female ratio was 10:8. The mean best corrected visual acuity was 0.18 LogMAR unit(s) and the mean spherical equivalent was +3.8 ± 0.14 diopters (D). The etiology of the esotropia was fully accommodative refractive esotropia (8), microtropia (1), post-operative infantile esotropia (4), partially accommodative esotropia (1), and post-operative partially accommodative esotropia (4). Patients received either office-based, home-based, or both modes of treatment for an average duration of 4.8 months (range 3-8). After therapy, BSV was achieved for either distance or near in 66.6 % of patients (95 % CI = 40.03-93.31 %). Binocular single vision for both distance and near was seen in 50 % of children. Qualified success was observed in 38.46% of patients. Persistence of suppression was observed in one patient (5.5 %). Near stereopsis improved to 200 s of arc or more in 60% of the patients. The mean esotropia reduced from 5.7 ± 4.0 PD for distance and 6.2 ± 4.66 PD for near to 2.7 ± 2.4 PD and 3.38 ± 4.7 PD respectively, at the last follow-up (p-value 0.004 and 0.006). Failure of therapy was noticed after six months of follow-up in the child with infantile esotropia. Anti-suppression exercises may be beneficial to improve binocular vision functions in children with small-angle esotropias of variable etiologies. Recurrence of suppression after cessation of therapy is possible, warranting regular follow up.


Participant Engagement and Reactance to a Short, Animated Video About Added Sugars: Web-based Randomized Controlled Trial.
Short, animated story-based (SAS) videos are a novel and promising strategy for promoting health behaviors. To gain traction as an effective health communication tool, SAS videos must demonstrate their potential to engage a diverse and global audience. In this study, we evaluate engagement with a SAS video about the consumption of added sugars, which is narrated by a child (a nonthreatening character), a mother (a neutral layperson), or a physician (a medical expert). This study aims to (1) assess whether engagement with the sugar intervention video differs by narrator type (child, mother, physician) and trait proneness to reactance and (2) assess whether the demographic characteristics of the participants (age, gender, education status) are associated with different engagement profiles with the sugar intervention video. In December 2020, after 4013 participants from the United Kingdom completed our randomized controlled trial, we offered participants assigned to the placebo arms (n=1591, 39.65%) the choice to watch the sugar intervention video (without additional compensation) as posttrial access to treatment. We measured engagement as the time that participants chose to watch the 3.42-minute video and collected data on age, gender, education status, and trait reactance proneness. Using ordinary least squares regression, we quantified the association of the demographic characteristics and trait reactance proneness with the sugar video view time. Overall, 66.43% (n=1047) of the 1576 participants in the 2 placebo arms voluntarily watched the sugar intervention video. The mean view time was 116.35 (52.4%) of 222 seconds. Results show that view times did not differ by narrator (child, mother, physician) and that older participants (aged 25-59 years, mean = 125.2 seconds) watched the sugar video longer than younger adults (aged 18-25 years, mean = 83.4 seconds). View time remained consistent across education levels. Participants with low trait reactance (mean = 119.3 seconds) watched the intervention video longer than high-trait-reactance participants (mean = 95.3 seconds), although this association did not differ by narrator type. The majority of participants in our study voluntarily watched more than half of the sugar intervention video, which is a promising finding. Our results suggest that SAS videos may need to be shorter than 2 minutes to engage people who are young or have high trait proneness to reactance. We also found that the choice of narrator (child, mother, or physician) for our video did not significantly affect participant engagement. Future videos, aimed at reaching diverse audiences, could be customized for different age groups, where appropriate. German Clinical Trials Register DRKS00022340; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022340. RR2-10.2196/25343.


Inhibition of antibody response to Pseudomonas exotoxin and an immunotoxin containing Pseudomonas exotoxin by 15-deoxyspergualin in mice.
Immunotoxins are potent cell-killing agents that may be useful in the treatment of cancer. The early production of neutralizing antibodies to immunotoxins is one of the major limiting factors for their use in humans. 15-Deoxyspergualin (DSG), a derivative of spergualin, which is a metabolite of Bacillus laterosporus, has been found to have immunosuppressive activity in rodents, dogs, and primates. We examined the suppressive activity of DSG on the antibody response to Pseudomonas exotoxin in mice by enzyme-linked immunosorbent assay. Male BDF1 mice were immunized with a single dose of a nontoxic mutant of Pseudomonas exotoxin (40 micrograms) and then treated with i.p. injections of DSF at a dose of 10 mg/kg for 3 days. Although antibodies to Pseudomonas exotoxin were observed within 7 days in the control group, there was complete suppression of antibody production in the DSG-treated group. Immunosuppression has also been observed in animals immunized with multiple doses (10 mg x 7 d) of Pseudomonas exotoxin and treated with DSG at a dose of 5 mg/kg for 21 days. Similar immunosuppression was observed in mice given multiple doses of the immunotoxin, anti-Tac-LysPE40. We conclude that the immunosuppressive activity of DSG may be useful in increasing the duration of immunotoxin treatment.


Acute and chronic neurological disorders in COVID-19: potential mechanisms of disease.
Coronavirus disease 2019 (COVID-19) is a global pandemic caused by SARS-CoV-2 infection and is associated with both acute and chronic disorders affecting the nervous system. Acute neurological disorders affecting patients with COVID-19 range widely from anosmia, stroke, encephalopathy/encephalitis, and seizures to Guillain-Barré syndrome. Chronic neurological sequelae are less well defined although exercise intolerance, dysautonomia, pain, as well as neurocognitive and psychiatric dysfunctions are commonly reported. Molecular analyses of CSF and neuropathological studies highlight both vascular and immunologic perturbations. Low levels of viral RNA have been detected in the brains of few acutely ill individuals. Potential pathogenic mechanisms in the acute phase include coagulopathies with associated cerebral hypoxic-ischaemic injury, blood-brain barrier abnormalities with endotheliopathy and possibly viral neuroinvasion accompanied by neuro-immune responses. Established diagnostic tools are limited by a lack of clearly defined COVID-19 specific neurological syndromes. Future interventions will require delineation of specific neurological syndromes, diagnostic algorithm development and uncovering the underlying disease mechanisms that will guide effective therapies.


A protein turnover signaling motif controls the stimulus-sensitivity of stress response pathways.
Stimulus-induced perturbations from the steady state are a hallmark of signal transduction. In some signaling modules, the steady state is characterized by rapid synthesis and degradation of signaling proteins. Conspicuous among these are the p53 tumor suppressor, its negative regulator Mdm2, and the negative feedback regulator of NFκB, IκBα. We investigated the physiological importance of this turnover, or flux, using a computational method that allows flux to be systematically altered independently of the steady state protein abundances. Applying our method to a prototypical signaling module, we show that flux can precisely control the dynamic response to perturbation. Next, we applied our method to experimentally validated models of p53 and NFκB signaling. We find that high p53 flux is required for oscillations in response to a saturating dose of ionizing radiation (IR). In contrast, high flux of Mdm2 is not required for oscillations but preserves p53 sensitivity to sub-saturating doses of IR. In the NFκB system, degradation of NFκB-bound IκB by the IκB kinase (IKK) is required for activation in response to TNF, while high IKK-independent degradation prevents spurious activation in response to metabolic stress or low doses of TNF. Our work identifies flux pairs with opposing functional effects as a signaling motif that controls the stimulus-sensitivity of the p53 and NFκB stress-response pathways, and may constitute a general design principle in signaling pathways.


Chromosome 13 abnormalities in multiple myeloma are mostly monosomy 13.
Chromosome 13 abnormalities are frequently observed in multiple myeloma (MM). Several reports recently demonstrated the strong prognostic value of these abnormalities, associated with a short survival. Cytogenetic studies have shown that most of these abnormalities are complete monosomies. In order to define the common minimal deletion, we analysed a series of 234 patients with MM using fluorescence in situ hybridization (FISH) with a panel of five probes mapping along the whole chromosome 13. A chromosome 13 abnormality was observed in 98 patients (42%), 90 of whom (92%) displayed a complete monosomy. In seven of the eight remaining patients presenting partial deletions, the three probes specific for the 13q14 region were deleted. Only one patient (1%) displayed a small deletion of the D13S319 locus. In conclusion, FISH should be used for the analysis of chromosome 13 abnormalities, using probes mapping in the 13q14 region.


Substantial long-term loss of alpha and gamma diversity of lake invertebrates in a landscape exposed to a drying climate.
Many regions across the globe are shifting to more arid climates. For shallow lakes, decreasing rainfall volume and timing, changing regional wind patterns and increased evaporation rates alter water regimes so that dry periods occur more frequently and for longer. Drier conditions may affect fauna directly and indirectly through altered physicochemical conditions in lakes. Although many studies have predicted negative effects of such changes on aquatic biodiversity, empirical studies demonstrating these effects are rare. Global warming has caused severe climatic drying in southwestern Australia since the 1970s, so we aimed to determine whether lakes in this region showed impacts on lake hydroperiod, water quality, and α, β and γ diversity of lake invertebrates from 1998 to 2011. Seventeen lakes across a range of salinities were sampled biennially in spring in the Wheatbelt and Great Southern regions of Western Australia. Multivariate analyses were used to identify changes in α, β and γ diversity and examine patterns in physicochemical data. Salinity and average rainfall partially explained patterns in invertebrate richness and assemblage composition. Climatic drying was associated with significant declines in lake depth, increased frequency of dry periods, and reduced α and γ diversity (γ declined from ~300 to ~100 taxa from 1998 to 2011 in the 17 wetlands). In contrast, β diversity remained consistently high, because each lake retained a distinct fauna. Mean α diversity per-lake declined both in lakes that dried and lakes that did not dry out, but lakes which retained a greater proportion of their maximum depth retained more α diversity. Accumulated losses in α diversity caused the decline in γ diversity likely through shrinking habitat area, fewer stepping stones for dispersal and loss of specific habitat types. Biodiversity loss is thus likely from lakes in drying regions globally. Management actions will need to sustain water depth in lakes to prevent biodiversity loss.


[Reticular structures of the cat brain participating in startle reflexes in response to somatic stimuli of different modalities].
Characteristics and reticular mechanisms of two types of late reflex responses (equivalents of the startle reflex) evoked by weak (tactile stimuli) and strong (high-threshold peripheral nerve stimulation) stimulations were studied in chloralose-anesthetized cats; these responses were designated as "tactile" (T) and "spino-bulbo-spinal" (SBS) reflexes, respectively. Some differences in the peripheral and central (brainstem) organization of these reflexes were found. In particular, the existence of the rostro-caudal differentiation of reticular structures involved in these types of reflexes was revealed using differential lesions of the brainstem reticular formation as well as its pharmacologic blockades (by means of microinjections of sodium chloride or procaine); the T-reflex was found to relay mainly through the pontine RF level, while the SBS-reflex--predominantly through the bulbar RF. Possible functional significance of the revealed differentiation in organization of some motor and sensory functions of the brainstem are discussed.


Two-year follow-up of a smoking cessation trial in patients with schizophrenia: increased rates of smoking cessation and reduction.
Long-term success rates of smoking cessation programs for patients with schizophrenia are unknown. This study, conducted between June 2001 and November 2002, evaluated the rate of smoking cessation and reduction in patients with schizophrenia (DSM-IV) 2 years after they had participated in a smoking cessation study in order to determine whether subjects who significantly reduced smoking during the original trial resumed their previous level of smoking at 2 years. Two years following a double-blind placebo-controlled trial of bupropion sustained release, 150 mg/day, added to cognitive-behavioral therapy for smoking cessation in patients with schizophrenia, subjects were interviewed, medical charts were reviewed, and carbon monoxide in expired air was measured. Seventeen of 18 subjects completed the follow-up assessment. More subjects were abstinent (22% [N = 4]) at the 2-year follow-up than were abstinent at the end of the trial (6% [N = 1]). Subjects who achieved significant smoking reduction during the trial were more likely to be abstinent at 2 years (4/7) than those who did not significantly reduce smoking during the trial (0/11) (chi(2) = 8.1, p <.005). Most subjects who achieved > or = 50% reduction in smoking at the end of the trial maintained at least that level of reduction at 2 years. Smoking reduction during the treatment intervention was correlated with smoking reduction at follow-up (r = 0.60, p =.01). The results from this naturalistic study suggest that behavior changes achieved in smoking cessation programs for patients with schizophrenia may be durable and may predict future smoking behavior. We conclude that further investigation into the relationship between smoking reduction and future smoking cessation in special populations is indicated.


Vaccine nanocarriers: Coupling intracellular pathways and cellular biodistribution to control CD4 vs CD8 T cell responses.
Nanoparticle delivery systems are known to enhance the immune response to soluble antigens (Ags) and are thus a promising tool for the development of new vaccines. Our laboratory has engineered two different nanoparticulate systems in which Ag is either encapsulated within the core of polymersomes (PSs) or decorated onto the surface of nanoparticles (NPs). Previous studies showed that PSs are better at enhancing CD4 T cells and antibody titers, while NPs preferentially augment cytotoxic CD8 T cells. Herein, we demonstrate that the differential activation of T cell immunity reflects differences in the modes of intracellular trafficking and distinct biodistribution of the Ag in lymphoid organs, which are both driven by the properties of each nanocarrier. Furthermore, we found that Ags within PSs promoted better CD4 T cell activation and induced a higher frequency of CD4 T follicular helper (Tfh) cells. These differences correlated with changes in the frequency of germinal center B cells and plasma cell formation, which reflects the previously observed antibody titers. Our results show that PSs are a promising vector for the delivery of Ags for B cell vaccine development. This study demonstrates that nanocarrier design has a large impact on the quality of the induced adaptive immune response.


Modeling microbial consortiums as distributed metabolic networks.
Biogeochemistry is the study of how living systems in combination with abiotic reactions process and cycle mass and energy on local, regional, and global scales (Schlesinger, 1997). Understanding how these biogeochemical cycles function and respond to perturbations has become increasingly important, as anthropogenic impacts have significantly altered many of these cycles (Galloway and Cowling, 2002; Houghton et al., 2002). Biogeochemistry is strongly governed by microbial processes, and it appears to closely follow thermodynamic constraints in that electron acceptor (O(2), NO(3)(-), SO(4)(2-), etc.) utilization closely follows a priori expectations based on energetics (Vallino et al., 1996; Hoehler et al., 1998; Jakobsen and Postma, 1999; Amend and Shock, 2001). Consortiums of microorganisms seem to have evolved to exploit chemical potentials wherever they exist in the environment, as manifested by the recent discovery of anaerobic methane oxidation by sulfate (Boetius et al., 2000) or sulfide oxidation by nitrate (Schulz et al., 1999). Three and a half billion years of natural selection have produced living systems capable of degrading most chemical potentials. We may therefore ask: If all ecosystem niche space is filled, is the biogeochemistry we observe in the environment dependent on the organisms that occupy that environment, or is the biogeochemistry determined by fundamental forces, with the evolution of living systems being the implementation of those forces? Recent developments in nonequilibrium thermodynamics (NET) are beginning to support the latter alternative, and advances in genomics are allowing us to explore microbial consortiums in detail. Taking advantage of ideas being suggested by NET, we have developed a modeling framework that views microbial consortiums as an inter-species distributed metabolic network. When combined with experimental observations, the model should help us test hypotheses that govern how living systems function.


Which body functions and activities matter for stroke patients? Study protocol for best-Worst scalings to value core elements of the International Classification of Functioning, Disability and Health.
Stroke is a common, serious, and disabling healthcare problem with increasing incidence and prevalence. Following a stroke, identifying the factors associated with decisions about rehabilitation interventions is important to assess rehabilitation after stroke. The aim is to guide clinical staff to make patient-centered decisions. Fundamentally, decision makers cannot draw on evidence to consider the relevance of distinct functions and activities from the patient's perspective. Until now, outcomes of rehabilitation are generally categorized using the International Classification of Functioning, Disability and Health (ICF). This can be seen as a conceptual basis for the assessment of health and disability. Since the ICF does not distinguish importance between these aspects there is a need to value the most important clinical factors as well as related activities from a patients and public perspective to help guide therapists in effectively designing post-acute rehabilitation care for individuals following stroke. The research question is which ICF body functions and activities are of value to stroke patients? Which trade-offs are patients willing to make within the core elements? Health preference research (HPR) answers the need to develop additional preference weights for certain ICF dimensions. Patient preference information (PPI) values health conditions based on the ICF from a patient perspective. In this study we conduct three best-worst scaling (BWS) experiments to value body function and activities from patients' and public perspective. Out of all ICF dimensions this research covers health conditions relevant to stroke patients in terms of body function, perception, and activities of daily living. Stroke patients as well as members of the general population will be recruited to participate in the online BWS surveys. Fractional, efficient designs are applied regarding the survey design. Conditional and multinominal logit analyses will be used as the main analysis method, with the best-worst count analysis as a secondary analysis. The survey is being piloted prior to commencing the process of data collection. Results are expected by the autumn of 2023. The research will add to the current literature on clinical decision-making in stroke rehabilitation and the value of certain body functions as well as related activities in neurorehabilitation. Moreover, the study will show whether body functions and activities that are currently equally weighted in international guidelines are also equally important from the point of view of those affected, or whether there are disconcordances in terms of differences between public judgements and patients' preferences.


Rippling Associated with Pre-Pectoral Implant Based Breast Reconstruction: A New Grading System.
The incidence of breast cancer and immediate breast reconstruction is on the rise particularly in the US and Western Europe. Over the last decade, implant based breast reconstructions have gained popularity. The prepectoral breast reconstruction has emerged as a novel technique, minimally invasive, preserves the chest wall anatomy while restoring body image. However, implant rippling appears to be an adverse effect associated with this technique. We have described a new grading system for rippling following prepectoral implant breast reconstruction and discussed its management. We then evaluated the new grading system in our practice. We looked at the first 50 consecutive patients who underwent prepectoral implant based breast reconstruction. In our experience, 45 patients (90%) had grade 1, 3 patients (6%) had grade 2, 1 patient (2%) had grade 3 and 1 patient (2%) had grade 4 rippling. The observed rippling was seen more often in patients with low BMI<20 and in those who had poor subcutaneous fat preoperatively (pinch test<2 cm). Prepectoral implant based breast reconstruction adds a whole new dimension to breast reconstruction. However rippling can be an undesired adverse effect associated with this technique and patients need to be informed.


Alpha-lipoic acid and its protective role in fructose induced endocrine-metabolic disturbances.
In recent decades a worldwide increase has been reported in the consumption of unhealthy high calorie diets associated with marked changes in meal nutrient composition, such as a higher intake of refined carbohydrates, which leads to the speculatation that changes in food habits have contributed to the current epidemic of obesity and type 2 diabetes. Among these refined carbohydrates, fructose has been deeply investigated and murine models of high fructose diet have emerged as useful tools to study dietary-induced insulin resistance, impaired glucose tolerance, dyslipidemia and alterations in glucose metabolism. Since oxidative stress has been demonstrated to play a key pathogenic role in the alterations described above, several lines of research have focused on the possible preventive effects of antioxidant/redox state regulation therapy, among which alpha-lipoic acid has been extensively investigated. The following references discussed support the fact that co-administration of alpha-lipoic acid normalized the changes generated by fructose rich diets, thereby making this compound a good therapeutic tool, also administered as a food supplement, to prevent endocrine-metabolic disturbances triggered by high fructose associated with obesity and type 2 diabetes at an early stage of development (prediabetes).


The effects of diet on the esterification of glycerol phosphate, dihydroxyacetone phosphate and 2-hexadecylglycerol by homogenates of rat adipose tissue.
1. Male rats were fed for 5 weeks after weaning on a diet containing (by weight) 59% of starch or on diets that contained 39% of starch and 20% of either sucrose, beef tallow or corn oil. 2. The rats fed on the beef tallow consumed more energy than did the rats fed on the starch and sucrose diets. The rats fed on the corn oil drank less water than did the other groups of rats. 3. There were no significant differences between the four groups in terms of body-weight gain, epididymal-fat-pad weight and in the size, number and triacylglycerol content of the adipocytes in the fat-pads. 4. There was a significant correlation (P less than 0.001) between the activities of glycerol phosphate acyltransferase and monoacylglycerol acyltransferase in individual rats. Both of these activities were highest in the group fed on the high-starch diet and both correlated with the consumption of glucose by individual rats in the four groups. 5. The percentage of glycerol phosphate converted into diacylglycerol and triacylglycerol was positively correlated with the mean diameters, surface area and triacylglycerol content of the adipocytes for individual rats and was greates in the sucrose-fed rats. 6. The specific activity of dihydroxyacetone phosphate acyltransferase was highest in the rats fed on beef tallow. This activity was positively correlated with the energy intake for all dietary groups over the 5-week feeding period. 7. The results are discussed in terms of the functions of the three routes of glycerolipid synthesis in adipose tissue.


Functional competence in major depressive disorder: Objective performance and subjective perceptions.
Major depressive disorder (MDD) is increasingly recognized as a disorder of everyday functioning. Multi-level approaches to investigating functioning have been employed in other conditions whereby competence (ability to perform living skills) is distinguished from real-world functioning, but not yet in MDD. We used a multidimensional (adaptive and interpersonal), multi-level (competence and performance) approach to investigate differences between those with MDD and healthy comparisons (HC) on measures of competence, functional disability, and self-perceived competence. Between-group analysis of variance identified differences between MDD (n = 42) and HC (n = 24). Moderation analysis determined whether the strength of the relationship between competence accuracy and self-perception of performance was related to group membership. In adaptive and interpersonal domains, the MDD group performed significantly lower on competence tasks, endorsed greater functional disability, and reported lower self-perception of competence. Group membership did not moderate the relationship between competence and self-perceived competence in the adaptive domain. Significant moderation was observed in the interpersonal domain such that competence and self-perception of abilities converged in the HC, but not MDD, group. A cross-sectional design precluded the ability to interpret causality of results. Functional disability was measured by interview, thereby susceptible to biases in self-report. A multi-level approach to assessing functioning in MDD was supported. Performance-based measures of functional competence are sensitive to MDD and useful for research trials and clinical work to objectively track everyday living skills. Objective measurement is further supported, as those with depression are less likely to accurately evaluate their own abilities, even after demonstrating skills.


Evaluation of Objective and Subjective Swallowing Outcomes in Patients with Dysphagia Treated for Head and Neck Cancer.
We evaluated objective and subjective swallowing function outcomes in patients with dysphagia treated for head and neck cancer (HNC) and identified risk factors for poor swallowing outcomes. Patients undergoing videofluoroscopic swallowing studies (VFSS) between January 2016 and March 2021 were divided into four groups according to primary tumor sites; post-treatment dysphagia was assessed. The penetration-aspiration scale (PAS) and bolus residue scale (BRS) were used to objectively assess swallowing function through VFSS. The Functional Oral Intake Scale (FOIS) was used for subjective analyses of swallowing statuses. To account for potential confounding, important covariates were adjusted for in logistic regression models. Oropharyngeal tumors were significantly more likely to have poor PAS and BRS scores than oral cavity tumors, and the patients with nasopharyngeal tumors were significantly less likely to have poor FOIS scores. Old age, having multiple HNCs, and a history of radiotherapy were associated with an increased odds of poor PAS scores (for all types of swallows), poor BRS scores (for semiliquid and solid swallows), and poor FOIS scores, respectively. This indicates using only subjective assessments may not allow for accurate evaluations of swallowing function in patients treated for HNC. Using both objective and subjective assessments may allow for comprehensive evaluations.


Detection of mitochondrial DNA mutations in the tumor and cerebrospinal fluid of medulloblastoma patients.
Medulloblastoma is the most common malignant brain tumor in children. Although the prognosis has improved considerably, leptomeningeal spread of the tumor remains a significantly negative predictor of survival. Mitochondrial DNA (mtDNA) mutations have been detected in many types of human tumors but not in medulloblastomas. Using temporal temperature gradient gel electrophoresis, we have analyzed the entire mitochondrial genome in 15 cases of medulloblastoma and the corresponding cerebrospinal fluid (CSF) samples in 8 of 15 cases. Six of 15 cases (40%) showed at least one mtDNA mutation in each of the tumors. A total of 18 somatic mtDNA mutations was detected with one of the tumors having 11 mutations, of which 9 were novel. Seven of 8 CSF samples that were analyzed showed mtDNA mutations. One patient who showed persistent mtDNA mutation in the CSF collected at the end of therapy when there was no evidence of disease had a relapse 5 months later. In contrast, patients whose end-of-therapy CSF samples that showed either no detectable mtDNA mutation or different mutations from that of the tumor continue to be disease free. Our results demonstrate that mtDNA mutations are frequently found in medulloblastomas. The mtDNA alterations detected in CSF may be used as sensitive markers to monitor disease progression and predict relapse.


The Gambian National Impregnated Bednet Programme: costs, consequences and net cost-effectiveness.
Clinical trials have indicated that treating mosquito nets with insecticide could be a potentially cost-effective method of preventing malaria. As malaria is one of the most common causes of death in children under five in developing countries, there has been substantial interest in whether such findings can be replicated for a country's control programme in practice. The cost-effectiveness of the Gambian National Insecticide-impregnated Bednet Programme (NIBP), from the viewpoint of providers (government and non-governmental agencies) and the community, has been calculated. Information was collected from existing records, interviews with NIBP personnel, observation and household surveys. Information is provided on the resource use consequences of the NIBP in terms of reduced expenditure on anti-malaria preventive measures, treatment in government health services, household financed treatment and "charity" (burial, funeral and mourning activities), as well as cash income lost as a result of child death. The annual implementation cost of the NIBP was D757,875 (US$91,864), of which 86% was recurrent cost. The estimated number of death averted was 40.56. The net implementation cost-effectiveness ratio per death averted and discounted life years gained were D3884 (US$471) and D260 (US$31.5), respectively. Adding the cost of all mosquito nets would increase the cost-effectiveness ratios by over five times, which is an important consideration for countries with a lower coverage of mosquito nets per capita. It is concluded that insecticide-impregnated mosquito nets are one of the more efficient ways of reducing deaths in children under 10 years in rural Gambia.


Association between expression of a tumor-associated carbohydrate epitope and the proliferative and tumorigenic activity of a human squamous lung cancer cell line and epitope-positive and -negative sublines.
A previously described epitope (designated 43-9F) with high specificity for human squamous carcinoma and adenocarcinoma of the lung is here reported to be associated with the proliferative and tumorigenic activity of a cloned human squamous lung carcinoma (SLC) cell line (SLC-L11) and a number of cloned sublines. Lines with appreciable 43-9F epitope density (43-9F+) had a short population doubling time and were tumorigenic in athymic nude mice, whereas clones with low 43-9F epitope density (43-9F-) of the same line had longer population doubling times and did not result in 43-9F- tumors in athymic nude mice. Some of the 43-9F- clones reverted to the 43-9F+ phenotype and then became tumorigenic. Two other SLC lines (SLC-L12 and SLC-L13), positive and negative, respectively, for 43-9F also expressed tumorigenic and proliferative behavior concordant with the data for SLC-L11 and its sublines. Cell lines of human squamous cell carcinomas had a pronounced intratumoral heterogeneity in respect to 43-9F epitope expression. Fluorescence-activated cell sorting of cells with high and low 43-9F density and subsequent cloning demonstrated that the cloning capacity was confined almost exclusively to cells with high antigen density. Immunoaffinity chromatography and gel filtration showed that the epitope was expressed in glycoproteins with molecular weights in the range of 5 X 10(6)-5 X 10(4). Mild alkaline hydrolysis reduced the binding of 43-9F antibody to SLC-glycoproteins while neuraminidase treatment augmented the 43-9F antibody binding. It is concluded that expression of 43-9F+ glycoproteins seems linked to the proliferative and tumorigenic features of human squamous lung carcinoma cell lines.


Comparison of two doses of intravitreal bevacizumab (Avastin) for treatment of macular edema secondary to branch retinal vein occlusion: results from the Pan-American Collaborative Retina Study Group at 6 months of follow-up.
To report the 6-month anatomical and visual outcomes after injecting two different doses of intravitreal bevacizumab in patients with macular edema secondary to branch retinal vein occlusion (BRVO). An interventional, retrospective multicenter study of 45 eyes that were treated with at least one intravitreal injection (24 eyes, 1.25 mg; 21 eyes, 2.5 mg) of bevacizumab is reported. The main outcome measures were the central 1-mm macular thickness (CMT) and the change in ETDRS lines of best-corrected visual acuity (BCVA) at 6 months. Forty-five eyes were injected on average 26.1 months (range, 3-86 months) after the diagnosis. The average follow-up was 35.2 weeks (range, 24-52 weeks). All patients completed at least 6 months of follow-up. In the 1.25-mg dose group, at 1 month, there was an average gain of 4.5 lines of BCVA; at 3 months, 5.1 lines of BCVA; and at 6 months, 5.1 lines of BCVA (P < 0.005). In the 2.5-mg dose group, at 1 month, there was an average gain of 2.3 lines of BCVA; at 3 months, 3.8 lines of BCVA; and at 6 months, 4.8 lines of BCVA (P = 0.05). In the 1.25-mg dose group, the mean CMT +/- SD decreased from 461 +/- 211 microm at baseline to 321 +/- 152 microm at 1 month, 273 +/- 99 microm at 3 months, and 277 +/- 114 microm at 6 months (P = 0.0002). In the 2.5-mg group, the mean CMT +/- SD decreased from 385 +/- 168 microm at baseline to 279 +/- 111 microm at 1 month, 249 +/- 97 microm at 3 months, and 240 +/- 93 microm at 6 months (P = 0.011). There were no statistically significant differences between the two dose groups with regard to the number of injections and anatomical and functional outcomes. Intravitreal injection of bevacizumab at doses up to 2.5 mg appears to be effective in improving BCVA and reducing CMT in BRVO in the short term. Multiple injections are needed in a large number of eyes for continued control of macular edema and preservation of visual acuity in the short term. Longer studies are needed to determine what role if any intravitreal injection of bevacizumab may play in the long-term treatment of this condition.


Protein C deficiency: summary of the 1995 database update.
The coagulation cascade is controlled by several anticoagulant safeguards that avoid excessive clot formation. Disorders of these anticoagulant mechanisms are an important health problem, as they lead to increased risk of thromboembolism. Protein C deficiency is probably the most extensively studied abnormality in natural anticoagulants. Under the auspices of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis a working party of researchers maintains a database of mutations that have been characterized in the protein C gene. The 1995 update of this database comprises 331 entries that describe 160 unique mutational events. Here essential features of the database are reviewed.


Knowledge and practice of radiation safety in Brazilian equine veterinarians are less than optimal: An online survey.
Exposure to ionizing radiation is an occupational risk for veterinarians due to the potential for carcinogenesis, reproductive disorders, cataracts, and hereditary genetic changes. This survey study aimed to identify the radiological protection practices routinely used by veterinarians who work with portable digital X-ray equipment in horses in Brazil and assess their knowledge regarding current legislation. A total of 120 voluntary participation questionnaires were sent to veterinarians who used portable digital radiographic equipment in horses nationwide. The frequencies of the answers were analyzed using the chi-square test and logistic regression models. Thirty-five veterinarians responded (29% response rate). Of these, there was a greater participation of professionals in public institutions (40%, 14/35, p < .001), with 69% from the southeast region (24/35, p < .001) and 69% (24/35, p = .028) being male. We found that self-employed veterinarians had a higher odds ratio (OR) (9.00; 95% confidence interval (CI) [1.39-58.44]; p = .021) of not using personal protective equipment compared with those in professional public institutions. In addition, not knowing the current legislation Collegiate Directorate Resolution 611/22 was a potential risk factor for lower radiological protection (OR, 8.00; 95% CI, [0.79-81.33]; p = 0.079). In conclusion, findings indicated that Brazilian equine veterinarians generally do not adopt adequate radiological protection against ionizing radiation during radiographic examinations and have low knowledge of the current legislation. Results can be used as background for the formulation of specific radiation protection guidelines for veterinarians and incentive educational and training strategies to reduce risks inherent to occupational exposure.


Role of precursor translocation in coordination of murein and phospholipid synthesis in Escherichia coli.
Inhibition of phospholipid synthesis in Escherichia coli by either cerulenin treatment or glycerol starvation of a glycerol-auxotrophic mutant resulted in a concomitant block of murein synthesis. The intracellular pool of cytoplasmic and lipid-linked murein precursors was not affected by an inhibition of phospholipid synthesis, nor was the activity of the penicillin-binding proteins. In addition, a decrease in the activity of the two lipoprotein murein hydrolases, the lytic transglycosylases A and B, could not be demonstrated. The indirect inhibition of murein synthesis by cerulenin resulted in a 68% decrease of trimeric muropeptide structures, proposed to represent the attachment points of newly added murein. Importantly, inhibition of phospholipid synthesis also inhibited O-antigen synthesis with a sensitivity and kinetics similar to those of murein synthesis. It is concluded that the step common for murein and O-antigen synthesis, the translocation of the respective bactoprenolphosphate-linked precursor molecules, is affected by an inhibition of phospholipid synthesis. Consistent with this assumption, it was shown that murein synthesis no longer depends on ongoing phospholipid synthesis in ether-permeabilized cells. We propose that the assembly of a murein-synthesizing machinery, a multienzyme complex consisting of murein hydrolases and synthases, at specific sites of the membrane, where integral membrane proteins such as RodA and FtsW facilitate the translocation of the lipid-linked murein precursors to the periplasm, depends on ongoing phospholipid synthesis. This would explain the well-known phenomenon that both murein synthesis and antibiotic-induced autolysis depend on phospholipid synthesis and thereby indirectly on the stringent control.


Multiplex, quantitative, real-time PCR assay for cytomegalovirus and human DNA.
We created a multiplex, quantitative, real-time PCR assay that amplifies cytomegalovirus (CMV) and human DNA in the same reaction tube, allowing for a viral load determination that is normalized to measured human DNA. The assay targets a conserved region of the CMV DNA polymerase gene that is not affected by known drug resistance mutations. All 36 strains of CMV detected by culture or qualitative PCR in a population of lung transplant recipients were detected. The assay detected 1 to 10 copies of CMV plasmid DNA. The analytic sensitivity was not affected by the presence of DNA from 10(6) human cells but was reduced approximately 10-fold by alkaline lysates of leukocyte preparations. CMV quantitation was linear over a range of 10(1) to 10(6) copies. The intraassay and interassay coefficients of variation were 29 and 40%. Human DNA was regularly detected in patient plasma samples, and the amount was increased by storage of blood at room temperature before plasma separation and by plasma separation techniques that allowed leukocyte contamination. Applied to whole blood, the assay provides a measurement of CMV DNA in relation to cellular content without a need for cell counting procedures. Applied to plasma, the assay can reveal artifactual increases in plasma CMV levels resulting from leukocyte contamination. Further study of the utility of this assay to monitor patient populations at risk for CMV disease is warranted.


Chromatin immunoprecipitation reveals that the 180-bp satellite repeat is the key functional DNA element of Arabidopsis thaliana centromeres.
The centromeres of Arabidopsis thaliana chromosomes contain megabases of complex DNA consisting of numerous types of repetitive DNA elements. We developed a chromatin immunoprecipitation (ChIP) technique using an antibody against the centromeric H3 histone, HTR12, in Arabidopsis. ChIP assays showed that the 180-bp centromeric satellite repeat was precipitated with the antibody, suggesting that this repeat is the key component of the centromere/kinetochore complex in Arabidopsis.


Weak C-HF-C hydrogen bonds make a big difference in graphane/fluorographane and fluorographene/fluorographane bilayers.
Using density functional theory computations with van der Waals (vdW) corrections, we reveal that C-HF-C hydrogen bonding exists in graphane/fluorographene and fluorographane/fluorographane bilayers. The significant C-HF-C hydrogen bonding is strong enough to combine two separate monolayers to form the bilayer. Interestingly, both the graphane/fluorographene and fluorographane/fluorographane bilayers are metallic in the most stable stacking configuration. Applying a perpendicular electric field can effectively open a bandgap for both bilayers, and we found that the field-induced gap opening for both graphane/fluorographene and fluorographane/fluorographane bilayers can be enhanced by biaxial tensile strain. These results are expected to aid in the design of novel electronic and optoelectronic devices based on graphene materials, and they highlight the use of weak interactions for modulating band structures in two-dimensional materials.


Fatty acid elongase 6 plays a role in the synthesis of long-chain fatty acids in goat mammary epithelial cells.
In nonruminants, it is well established that elongation of very long-chain fatty acid-like fatty acid elongase 6 (ELOVL6) catalyzes the synthesis of C18:0 from C16:0 in lipogenic tissues like adipose and liver. However, the role of ELOVL6 in regulating lipid metabolism in ruminant mammary gland remains unknown. In the present study, ELOVL6 was overexpressed or knocked down via adenoviral transfection to assess its role in goat mammary epithelial cells. Results revealed that ELOVL6 overexpression had a weak effect on the expression of genes related to triacylglycerol (TAG) synthesis and desaturation. Overexpression of ELOVL6 increased the content of C18:0 at the expense of C16:0, and increased the elongation index of C16:0. Overexpression of ELOVL6 had no significant effect on the elongation index of C16:1n-7 and the desaturation indices of C16:0 and C18:0. Knockdown of ELOVL6 had a negative effect on mRNA expression of the esterification genes GPAM and diacylglycerolacyltransferase 2 (DGAT2) and TAG concentration; however, it increased the concentration of C16:0 and decreased C18:1n-7 and C18:1n-9 in goat mammary epithelial cells. Accordingly, downregulation of ELOVL6 significantly decreased the elongation indices of C16:0 and C16:1n-7. The lack of change in the desaturation indices of C16:0 and C18:0 upon knockdown of ELOVL6 was consistent with the minor change in SCD1 expression. In conclusion, these are the first results highlighting an important role of ELOVL6 in long-chain fatty elongation and TAG synthesis in ruminant mammary cells.


Ankle Dorsiflexion Displacement During Landing is Associated With Initial Contact Kinematics but not Joint Displacement.
The ankle, knee, and hip joints work together in the sagittal plane to absorb landing forces. Reduced sagittal plane motion at the ankle may alter landing strategies at the knee and hip, potentially increasing injury risk; however, no studies have examined the kinematic relationships between the joints during jump landings. Healthy adults (N = 30; 15 male, 15 female) performed jump landings onto a force plate while three-dimensional kinematic data were collected. Joint displacement values were calculated during the loading phase as the difference between peak and initial contact angles. No relationship existed between ankle dorsiflexion displacement during landing and three-dimensional knee and hip displacements. However, less ankle dorsiflexion displacement was associated with landing at initial ground contact with larger hip flexion, hip internal rotation, knee flexion, knee varus, and smaller plantar flexion angles. Findings of the current study suggest that restrictions in ankle motion during landing may contribute to contacting the ground in a more flexed position but continuing through little additional motion to absorb the landing. Transverse plane hip and frontal plane knee positioning may also occur, which are known to increase the risk of lower extremity injury.


The unfulfilled promises of electronic health records.
We provide a brief update on the current evidence on electronic health records' benefits, risks, and potential harms through a rapid narrative review. Many of the promised benefits of electronic health records have not yet been realised. Electronic health records are often not user-friendly. To enhance their potential, electronic health record platforms should be continuously evaluated and enhanced by carefully considering feedback from all stakeholders.


The effects of melatonin on the physical properties of bones and egg shells in the laying hen.
Laying hens often experience unbalanced calcium utilization which can cause deficiencies in bone and egg mineralization. Because melatonin has been shown to affect bone mineralization in other animals, we examined whether treating hens with melatonin would affect eggshell thickness and improve skeletal performance, thereby reducing skeletal and egg shell defects. Birds were given a diet containing either low (30 µg/kg), medium (300 µg/kg), or high (3 mg/kg) concentrations of melatonin, or control feed through approximately one laying cycle. We examined the weight, length, and strength of egg, femur, tibia, and keel. Hens treated with a high concentration of melatonin showed significant strengthening in their femur and tibia, as measured by maximum force sustained and breaking force, compared to controls. Egg weights from hens treated with melatonin were significantly greater than those from hens that were not treated with melatonin. Conversely, egg shell mass of hens treated with melatonin was significantly lower than those of hens not treated with melatonin. Our data suggest that melatonin may affect the allocation of calcium to bone at the expense of egg shell mineralization.


Recent increase of ulcerative lesions caused by Anisakis spp. in cetaceans from the north-east Atlantic.
Species of Anisakis typically infect the stomach of cetaceans worldwide, often causing ulcerative lesions that may compromise the host's health. These nematodes also cause anisakiasis or allergic reactions in humans. To assess the risks of this emerging zoonosis, data on long-term changes in Anisakis infections in cetaceans are necessary. Here, we compare the prevalence and severity of ulcerative lesions caused by Anisakis spp. in five cetacean species stranded along the north-west Spanish coast in 2017-2018 with published data from 1991-1996. Open ulcers were found in 32/43 short-beaked common dolphins, Delphinus delphis; 3/5 striped dolphins, Stenella coeruleoalba; 1/7 bottlenose dolphins, Tursiops truncatus; and 1/3 harbour porpoises, Phocoena phocoena meridionalis; a single individual of long-finned pilot whale, Globicephala melas, was found uninfected. In common dolphins, the mean abundance of open ulcers per host was 1.1 (95% confidence interval: 0.8-1.3), with a maximum diameter (mean ± standard deviation) of 25.4 ± 16.9 mm. Stomachs with scars or extensive fibrosis putatively associated with Anisakis were detected in 14 and five animals, respectively. A molecular analysis based on the mitochondrial cytochrome c oxidase II gene using 18 worms from three cetacean species revealed single or mixed infections of Anisakis simplex sensu stricto and Anisakis pegreffii. Compared with the period 1991-1996, we found a strong increase of prevalence, abundance and extension of ulcerative lesions in most cetacean species. Anisakis populations could have increased in the study area over the last decades, although we cannot rule out that a higher environmental stress has also boosted the pathological effects of these parasites.


Advanced liquid electrolytes enable practical applications of high-voltage lithium-metal full batteries.
High-voltage lithium metal batteries (HVLMBs) have received widespread attention as next generation high-energy-density batteries to meet the urgent demands of modern life. However, the unstable interphase between electrolytes and highly reactive electrodes is still an important threshold for practical applications. In this feature article, we review the formation mechanism of the electrode-electrolyte interphase in terms of cathodes and the Li metal anode, respectively, and summarize the surface modification methods to stabilize the interphase of HVLMBs. Electrolyte regulation strategies especially those using electrolyte additives are introduced, and the relationship between liquid electrolyte formulation, interphase engineering and the electrochemical performance of HVLMBs is analyzed. Finally, an industry-level evaluation is carried out and the remaining challenges are discussed for advanced electrolytes to guarantee the practical applications and commercialization of HVLMBs.


The Upstate New York Surgical Quality Improvement Opioid Reduction Project.
Over 5 million Americans currently abuse prescription opioids. Patients' first exposure to opioids is often after surgery. Few opioid guidelines account for the challenges to health care institutions that serve wide catchment areas. We standardized postoperative opioid prescribing recommendations amongst surgical providers at our institutions and analyzed postoperative prescribing habits. The Upstate New York Surgical Quality Improvement (UNYSQI) collaborative met with surgical champions from 16 hospitals to standardize opioid prescribing for 21 surgical procedures. The guidelines were distributed to all surgical care providers at participating institutions. 581,465 pills were dispensed for 12,672 surgeries (average of 45.9 pills per procedure) before implementation. Post-implementation, 1,097,849 pills were dispensed for 28,772 surgeries (average of 38.2 pills per surgery) with over 222,000 fewer pills being prescribed. Our project suggests opioid prescribing guidelines for institutions that serve diverse communities.


Genistein prevents the glucose autoxidation mediated atherogenic modification of low density lipoprotein.
Hyperglycemia has been assumed to be responsible for oxidative stress in diabetes. In this respect, glucose autoxidation and advanced glycation end products (AGE) may play a causal role in the etiology of diabetic complications as e.g. atherosclerosis. There is now growing evidence that the oxidative modification of LDL plays a potential role in atherogenesis. Glucose derived oxidants have been shown to peroxidise LDL. In the present study, genistein, a compound derived from soy with a flavonoid chemical structure (4', 5, 7-trihydroxyisoflavone) has been evaluated for its ability to act as an antioxidant against the atherogenic modification of LDL by glucose autoxidation radical products. Daidzein, (4',7-dihydroxyisoflavone) an other phytoestrogen of soy, was tested in parallel. Genistein--in contrast to daidzein--effectively prevented the glucose mediated LDL oxidation as measured by thiobarbituric acid-reactive substance formation (TBARS), alteration in electrophoretic mobility, lipid hydroperoxides and fluorescence quenching of tryptophan residues of the lipoprotein. In addition the potential of glucose-oxidized LDL to increase tissue factor (TF) synthesis human endothelial cells (HUVEC) was completely inhibited when genistein was present during LDL oxidative modification by glucose. Both phytoestrogens did not influence the nonenzymatic protein glycation reaction as measured by the in vitro formation of glycated LDL. As the protective effect of genistein on LDL atherogenic modification was found at glucose/genistein molar ratios which may occur in vivo, our findings support the suggested beneficial action of a soy diet in preventing chronic vascular diseases and early atherogenic events.


Student performance and grading changes in a systems-based curriculum.
Changing from a conventional discipline-based, basic science medical school curriculum to an integrated systems-based curriculum, which was graded on overall performance not by discipline, was associated with a highly significant improvement in an externally administered comprehensive exam at the end of the 2-year basic science program. The reason for the improvement was unclear, but we hypothesized that it was partly due to a change in student study strategy. Anecdotal evidence suggested that students had changed their study habits to spend less time on previously harder-to-pass courses and more time on courses with previously lower failure rates. If this were so, performance in previously harder disciplines might have deteriorated, while performance in previously easier disciplines could have improved. We examined relative performance in the four discipline-based courses of Systemic Pathology, Microbiology, Pharmacology, and Introductory Clinical Medicine (ICM) in the fourth (and last) semester of the curriculum. We compared failure rates in these four courses for the three cohorts before the change with the three cohorts after. Pharmacology and Microbiology which had failure rates over twice as high as Systemic Pathology and ICM in the conventional program before the curriculum change showed a deterioration in performance after the change with an approximately threefold rise in internal failure rate. In contrast, Systemic Pathology showed a dramatic improvement with a more than threefold drop in the failure rate, while the ICM clinical skills course, which was largely assessed by a practical exam in all 6 cohorts, showed no change. The improvement in student performance in an external assessment may be due, at least partly, to a change in the school's internal grading policy which led to a more appropriate balancing of student study strategies. Future studies on the effect of curriculum change should include an assessment of the impact on student study strategies.


Instruments for predicting visual acuity. A clinical comparison.
A series of 54 eyes in 50 patients had preoperative predictions of postoperative visual acuity, using both a white-light interferometer (Lotmar Visometer) and a Snellen chart projector (Guyton-Minkowski Potential Acuity Meter). The predicted vision by each instrument was compared with the actual postoperative vision. Forty eyes in 36 of these patients, 25 with concurrent eye disease, had cataract extraction with intraocular lens implantation. Fifteen eyes in 15 patients, 11 with concurrent eye disease, had neodymium-YAG laser posterior capsulotomy. The Visometer gave more accurate predictions than the Potential Acuity Meter in cataract patients with open angle glaucoma, even with glaucomatous visual field loss, and in patients with a visual acuity of less than 20/400 due to advanced cataract formation.


Plasma pharmacokinetics of cyclophosphamide and its cytotoxic metabolites after intravenous versus oral administration in a randomized, crossover trial.
Since cyclophosphamide is used by both oral and i.v. routes in the treatment of hematological and solid malignancies, we designed a randomized, crossover clinical trial to evaluate the pharmacokinetics of this anticancer agent after either administration route. Plasma levels of cyclophosphamide and its two cytotoxic metabolites, 4-hydroxycyclophosphamide and phosphoramide mustard, were determined in seven cancer patients randomly assigned to treatment initially with either orally or i.v. administered cyclophosphamide with a 30-day interim between alternate therapy courses. Oral treatment was used initially in five patients and i.v. treatment in two patients, and the pharmacokinetic parameter, area under the plasma disappearance curve, was determined for each metabolite in each patient for both routes of drug administration. Statistical comparison of area under the plasma disappearance curve values for this set of patients indicated no significant differences for either metabolite for oral versus i.v. drug treatment, suggesting equal efficacy for these two routes of cyclophosphamide administration.