The availability of surface GABA B receptors is independent of gamma-aminobutyric acid but controlled by glutamate in central neurons.
The efficacy of synaptic transmission depends on the availability of ionotropic and metabotropic neurotransmitter receptors at the plasma membrane, but the contribution of the endocytic and recycling pathways in the regulation of gamma-aminobutyric acid type B (GABA(B)) receptors remains controversial. To understand the mechanisms that regulate the abundance of GABA(B) receptors, we have studied their turnover combining surface biotin labeling and a microscopic immunoendocytosis assay in hippocampal and cortical neurons. We report that internalization of GABA(B) receptors is agonist-independent. We also demonstrate that receptors endocytose in the cell body and dendrites but not in axons. Additionally, we show that GABA(B) receptors endocytose as heterodimers via clathrin- and dynamin-1-dependent mechanisms and that they recycle to the plasma membrane after endocytosis. More importantly, we show that glutamate decreases the levels of cell surface receptors in a manner dependent on an intact proteasome pathway. These observations indicate that glutamate and not GABA controls the abundance of surface GABA(B) receptors in central neurons, consistent with their enrichment at glutamatergic synapses.


Incommensurately modulated twin structure of nyerereite Na1.64K0.36Ca(CO3)2.
The incommensurately modulated twin structure of nyerereite Na1.64K0.36Ca(CO3)2 has been first determined in the (3 + 1)-dimensional symmetry group Cmcm(α00)00s with modulation vector q = 0.383a*. Unit-cell values are a = 5.062 (1), b = 8.790 (1), c = 12.744 (1) Å. Three orthorhombic components are related by threefold rotation about [001]. Discontinuous crenel functions are used to describe the occupation modulation of Ca and some CO3 groups. The strong displacive modulation of the O atoms in vertexes of such CO3 groups is described using x-harmonics in crenel intervals. The Na, K atoms occupy mixed sites whose occupation modulation is described in two ways using either complementary harmonic functions or crenels. The nyerereite structure has been compared both with the commensurately modulated structure of K-free Na2Ca(CO3)2 and with the widely known incommensurately modulated structure of γ-Na2CO3.


Two-dimensional ferroelectric MoS2/Ga2O3 heterogeneous bilayers with highly tunable photocatalytic and electrical properties.
Two-dimensional van der Waals heterostructures with strong intrinsic ferroelectrics are highly promising for novel devices with designed electronic properties. The polarization reversal transition of the 2D ferroelectric Ga2O3 monolayer offers a new approach to tune the photocatalytic and electrical properties of MoS2/Ga2O3 heterogeneous bilayers. In this work, we study MoS2/Ga2O3 heterogeneous bilayers with different intrinsic polarization using hybrid-functional calculations. We closely investigate the structural, electronic and optical properties of two stable stacking configurations with opposite polarization. The results reveal a distinct switch from type-I to type-II heterostructures owing to polarization reversal transition of the 2D ferroelectric Ga2O3 monolayer. Biaxial strain engineering leads to type-I-to-II and type-II-to-III transitions in the two polarized models, respectively. Intriguingly, one of the MoS2/Ga2O3 heterolayers has a larger spatial separation of the valence and conduction band edges and excellent optical absorption ranging from infrared to ultraviolet region under biaxial strain, thus ensuring promising novel applications such as flexible electrical and optical devices. Based on the highly tunable physical properties of the bilayer heterostructures, we further explore their potential applications, such as photocatalytic water splitting and field-controlled switch channel in MOSFET devices.


Ellagic acid, a natural polyphenol protects rat peripheral blood lymphocytes against nicotine-induced cellular and DNA damage in vitro: with the comparison of N-acetylcysteine.
The present work is aimed at evaluating the protective effect of ellagic acid (EA), a natural polyphenolic compound that is widely distributed in fruits and nuts against nicotine-induced toxicity in rat peripheral blood lymphocytes. The effect of EA against nicotine toxicity was compared with N-acetylcysteine (NAC), a well-known antioxidant. Lymphocytes were exposed to nicotine at the doses of 0.125, 0.25, 0.5, 1, 2, 3 and 4 mM for 1h in culture media. Thiobarbituric acid reactive substances (TBARS), a lipid peroxidative marker and reduced glutathione (GSH), as indicative of endogenous antioxidant status were analyzed to fix the optimum dose. The lowest concentration eliciting significant damage was 1 mM nicotine and maximum damage was observed with 3 mM concentration, as evidenced by increased levels of TBARS and decreased levels of GSH. Hence, the test concentration was fixed at 3 mM nicotine. To establish most effective protective support we used five different concentrations of EA (10, 50, 100, 150 and 300 microM) against 3 mM nicotine. A dose-dependent inhibitory effect was observed with all doses of EA. Maximum protection was observed at the dose of 100 microM EA. So, 100 microM dose was used for further studies. We have tested five different concentrations of NAC-0.25, 0.5, 1, 2 and 4 mM to elucidate the optimum protective dose against nicotine toxicity. One millimolar NAC showed a significant protection against nicotine toxicity. Protective effect of EA against nicotine toxicity was elucidated by analyzing the lipid peroxidative index, viz., TBARS, hydroperoxides (HP) and endogenous antioxidant status, viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), Vitamins A, E and C. DNA damage and repair were assessed by using alkaline single-cell microgel electrophoresis (Comet assay) and micronucleus assay. There was a significant increase in the levels of lipid peroxidative index, severity in DNA damage and micronuclei number in nicotine-treated group, which was positively modulated by EA treatment. Antioxidant status was significantly depleted in nicotine-treated group, which was effectively restored by EA treatment. The protection of EA against nicotine toxicity was equally effective to that of NAC. EA and NAC treatment alone did not produce any damage to the normal lymphocytes at their effective doses. These findings suggest the potential use and benefit of EA as a modifier of nicotine-induced genotoxicity.


Progressive plasticity during colorectal cancer metastasis.
Metastasis is the principal cause of cancer death, yet we lack an understanding of metastatic cell states, their relationship to primary tumor states, and the mechanisms by which they transition. In a cohort of biospecimen trios from same-patient normal colon, primary and metastatic colorectal cancer, we show that while primary tumors largely adopt LGR5 + intestinal stem-like states, metastases display progressive plasticity. Loss of intestinal cell states is accompanied by reprogramming into a highly conserved fetal progenitor state, followed by non-canonical differentiation into divergent squamous and neuroendocrine-like states, which is exacerbated by chemotherapy and associated with poor patient survival. Using matched patient-derived organoids, we demonstrate that metastatic cancer cells exhibit greater cell-autonomous multilineage differentiation potential in response to microenvironment cues than their intestinal lineage-restricted primary tumor counterparts. We identify PROX1 as a stabilizer of intestinal lineage in the fetal progenitor state, whose downregulation licenses non-canonical reprogramming.


Light Harvesting and Photocurrent Generation in a Conjugated Polymer Nanoparticle-Reduced Graphene Oxide Composite.
Polymer-graphene nanocomposites are promising candidates for light harvesting applications such as photocatalysis and photovoltaics, where significant charge separation occurs due to photoinduced electron transfer. Much attention has been paid to using reduced graphene oxide (r-GO) as template for anchoring various nanomaterials due to its efficient electron accepting and transport properties. Here, poly[2-methoxy-5-(2-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) nanoparticles are prepared from MEH-PPV polymer and the change in photophysical properties upon formation of polymer nanoparticles (PNPs) from the molecular state are investigated by using steady-state and time-resolved spectroscopy. Nanocomposites are constructed by adding hexadecylamine-functionalized positively charged MEH-PPV PNPs to a solution of negatively charged r-GO. Steady-state and time-resolved spectroscopy are also used to study the electronic interactions between PNPs and r-GO. Ultrafast femtosecond up-conversion and transient absorption spectroscopy unequivocally confirms the electron transfer process from the excited state of MEH-PPV PNPs to r-GO at the interface of the nanocomposite. Analysis reveals that the charge separation time is found to be pulse-width-limited (<100 fs). Due to charge separation in these nanocomposites, an increase (2.6 fold) of photocurrent under visible light illumination is obtained. The fundamental understanding of the charge transfer dynamics affords new opportunities to design efficient light-harvesting systems based on inorganic-organic hybrids.


Communication in context: effects of speaker status on the comprehension of indirect requests.
Four experiments were conducted to examine how a speaker's status can affect the comprehension of conventional and nonconventional indirect requests. The processing of conventional forms was not affected by the speaker's relative status, and consistent with past research (R. W. Gibbs, 1983), these forms were recognized quickly and without the hearer recognizing and then rejecting the literal meaning of the remark. In contrast, processing of nonconventional forms was affected by speaker status. When the interactants were equal in status, the comprehension of nonconventional forms was time-consuming and involved activation of the remark's literal meaning. This did not occur when the speaker was higher in status than the hearer. Results illustrate the role played by the interpersonal context in the comprehension of certain indirect requests.


A Novel Inflammatory lncRNAs Prognostic Signature for Predicting the Prognosis of Low-Grade Glioma Patients.
As immunotherapy has received attention as new treatments for brain cancer, the role of inflammation in the process of glioma is of particular importance. Increasing studies have further shown that long non-coding RNAs (lncRNAs) are important factors that promote the development of glioma. However, the relationship between inflammation-related lncRNAs and the prognosis of glioma patients remains unclear. The purpose of this study is to construct and validate an inflammation-related lncRNA prognostic signature to predict the prognosis of low-grade glioma patients. By downloading and analyzing the gene expression data and clinical information of the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) patients with low-grade gliomas, we could screen for inflammatory gene-related lncRNAs. Furthermore, through Cox and the Least Absolute Shrinkage and Selection Operator regression analyses, we established a risk model and divided patients into high- and low-risk groups based on the median value of the risk score to analyze the prognosis. In addition, we analyzed the tumor mutation burden (TMB) between the two groups based on somatic mutation data, and explored the difference in copy number variations (CNVs) based on the GISTIC algorithm. Finally, we used the MCPCounter algorithm to study the relationship between the risk model and immune cell infiltration, and used gene set enrichment analysis (GSEA), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the enrichment pathways and biological processes of differentially expressed genes between the high- and low-risk groups. A novel prognostic signature was constructed including 11 inflammatory lncRNAs. This risk model could be an independent prognostic predictor. The patients in the high-risk group had a poor prognosis. There were significant differences in TMB and CNVs for patients in the high- and low-risk groups. In the high-risk group, the immune system was activated more significantly, and the expression of immune checkpoint-related genes was also higher. The GSEA, GO, and KEGG analyses showed that highly expressed genes in the high-risk group were enriched in immune-related processes, while lowly expressed genes were enriched in neuromodulation processes. The risk model of 11 inflammation-related lncRNAs can serve as a promising prognostic biomarker for low-grade gliomas patients.


Banting Lecture. Hypoglycemia: the limiting factor in the management of IDDM.
Iatrogenic hypoglycemia is the limiting factor in the management of insulin-dependent diabetes mellitus (IDDM). It causes recurrent physical morbidity, some mortality, and recurrent or even persistent psychosocial morbidity. The principles of glucose counterregulation, the physiological mechanisms that normally very effectively prevent or correct hypoglycemia, are now known. Decrements in insulin, increments in glucagon, and, in the absence of the latter, increments in epinephrine stand high in the hierarchy of redundant glucose counterregulatory factors. Iatrogenic hypoglycemia in IDDM is the result of the interplay of absolute or relative therapeutic insulin excess and compromised glucose counterregulation. Syndromes of compromised glucose counterregulation include defective glucose counterregulation (the result of combined deficiencies of the glucagon and epinephrine responses to falling glucose levels), hypoglycemia unawareness (loss of the warning, neurogenic symptoms of developing hypoglycemia), and elevated glycemic thresholds (lower glucose levels required) for autonomic activation and symptoms during effective intensive therapy. These have been conceptualized as examples of hypoglycemia-associated autonomic failure, a functional disorder distinct from classical diabetic autonomic neuropathy, in IDDM. Recent antecedent iatrogenic hypoglycemia appears to be a major factor in the pathogenesis of hypoglycemia unawareness; there is increasing evidence that this syndrome is reversible with scrupulous avoidance of hypoglycemia. It probably also contributes substantially to the syndrome of elevated glycemic thresholds during intensive therapy. However, factors in addition to recent antecedent hypoglycemia play an important role in the pathogenesis of the syndrome of defective glucose counterregulation. Pending the prevention and cure of IDDM, we need to learn to replace insulin in a much more physiological fashion and/or to prevent, correct, or compensate for compromised glucose counterregulation if we are to eliminate hypoglycemia from the lives of people with IDDM without compromising glycemic control. In the meantime, we must continue to seek better insight into the fundamental mechanisms of compromised glucose counterregulation and to develop practical preventive clinical strategies and practice hypoglycemia risk factor reduction with our patients.


Potential antiinflammatory effects of interleukin 4: suppression of human monocyte tumor necrosis factor alpha, interleukin 1, and prostaglandin E2.
Stimulated human monocytes/macrophages are a source of mediators such as tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and prostaglandin E2 (PGE2), which can modulate inflammatory and immune reactions. Therefore, the ability to control the production of such mediators by monocytes/macrophages may have therapeutic benefits, and it has been proposed that glucocorticoids may act in this way. Purified human monocytes, when stimulated in vitro with lipopolysaccharide (LPS) or with LPS and gamma interferon (IFN-gamma), produce TNF-alpha, IL-1, and PGE2. Cotreatment of stimulated cells with the purified human lymphokine, interleukin 4 (IL-4 greater than or equal to 0.1-0.5 unit/ml; 12-60 pM) dramatically blocked the increased levels of these three mediators; for TNF-alpha and IL-1, the inhibition was manifest at the level of mRNA. Thus, IL-4 can suppress some parameters of monocyte activation and, as for B cells, have opposite effects to IFN-gamma. The effects of IL-4 on human monocytes are similar to those obtained with the glucocorticoid dexamethasone (0.1 microM).


[Prospective study of the direct and indirect costs of idiopathic Parkinson's disease].
Idiopathic Parkinson's disease is a chronic progressive neurodegenerative disorder that remains refractory to curative treatment. Most patients are afflicted for many years, and the disease frequently results in severe physical handicap. Statements on the considerable cost of treatment are largely based on estimates and retrospective studies. To obtain more substantial data, we conducted a 3-year study of the economic aspects. Direct and indirect costs incurred by 117 patients (78 male, mean age 67.5 years) at the Deutsche Klinik für Diagnostik in Wiesbaden, Germany, were prospectively followed. The average cost per patient and month ran to <euro> 1007.55. Of that, direct costs amounted to <euro> 603.33 (55.9%), with drugs taking up the major share at <euro> 480.23. Indirect costs were <euro> 404.22 per patient and month, with 76% thereof related to nursing care and the incapacity to earn a living. Cost increased in proportion to Hoehn and Yahr stage, declining again with stages 4 and 5. The data we gathered confirm that Parkinsonism is responsible for sizeable expenses for not only the treating unit but the national economy as a whole.


In vitro reaction of hydroxyamino derivatives of MeIQx, Glu-P-1 and Trp-P-1 with DNA: 32P-postlabelling analysis of DNA adducts formed in vivo by the parent amines and in vitro by their hydroxyamino derivatives.
The synthetic hydroxyamino derivatives of three mutagenic and carcinogenic heterocyclic amines present in cooked foods and amino acid pyrolysates, 2-amino-3,8-dimethylimidazo-[4,5-f]quinoxaline (MeIQx), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), were reacted with DNA in vitro. Their reactivities were increased by addition of 10-fold excess of acetic anhydride. 32P-Postlabelling analysis of the adducts formed in these in vitro reactions revealed that almost all the adducts of the hydroxyamino derivatives of MeIQx and Glu-P-1 were the same as those formed in liver DNA of rats intragastrically treated with the parent amines. In contrast, analysis of Trp-P-1--DNA adducts showed that the adducts formed in vitro were minor components of those formed in vivo; the two main adducts formed in vivo were not formed in vitro. Thus, MeIQx and Glu-P-1 may be metabolized in vivo to hydroxyamino derivatives and/or their esterified forms, such as N-acetoxy derivatives that form DNA adducts. Formation of adducts by Trp-P-1, however, may occur through more complicated metabolic pathways. Elucidation of the structures of DNA adducts in vivo is necessary to clarify this problem.


High-resolution sequencing and modeling identifies distinct dynamic RNA regulatory strategies.
Cells control dynamic transitions in transcript levels by regulating transcription, processing, and/or degradation through an integrated regulatory strategy. Here, we combine RNA metabolic labeling, rRNA-depleted RNA-seq, and DRiLL, a novel computational framework, to quantify the level; editing sites; and transcription, processing, and degradation rates of each transcript at a splice junction resolution during the LPS response of mouse dendritic cells. Four key regulatory strategies, dominated by RNA transcription changes, generate most temporal gene expression patterns. Noncanonical strategies that also employ dynamic posttranscriptional regulation control only a minority of genes, but provide unique signal processing features. We validate Tristetraprolin (TTP) as a major regulator of RNA degradation in one noncanonical strategy. Applying DRiLL to the regulation of noncoding RNAs and to zebrafish embryogenesis demonstrates its broad utility. Our study provides a new quantitative approach to discover transcriptional and posttranscriptional events that control dynamic changes in transcript levels using RNA sequencing data.


[The effect of subjective urinary symptoms on quality of life (QOL)--results of a field survey for prostatic diseases].
We investigated the effect of subjective urinary symptoms on quality of life (QOL) in 536 males who participated in a field survey for prostatic diseases in Hokkaido from 1991 to 1993. To quantitatively estimate the subjective urinary symptoms, we used a questionnaire that included questions about irritative symptoms such as "diurnal frequency", "nocturia", "sensation of residual urine", "urgency" and "frequent urination within 2 hrs.", and obstructive symptoms such as "difficulty to start urination", "intermittency during urination", "strain or pushing", "weak stream" and "stopping or starting urination". The incidences of participants with poor QOL increased as irritative and obstructive symptoms became apparent (p < 0.001). However, some participants, who had only mild urinary symptoms, could not tolerate the situation and felt impairment of QOL. In contrast, others did not feel a decrease of QOL in daily life in spite of severe symptoms. Thus, subjective urinary symptoms did not always correlate with QOL in some individuals. These results indicated that we should keep in mind not only subjective urinary symptoms but their effect on QOL whenever we determine an indication for medical or surgical intervention for patients having urinary symptoms.


Identification of Novel STAT6-Regulated Proteins in Mouse B Cells by Comparative Transcriptome and Proteome Analysis.
The transcription factor STAT6 plays a key role in mediating signaling downstream of the receptors for IL-4 and IL-13. In B cells, STAT6 is required for class switch recombination to IgE and for germinal center formation during type 2 immune responses directed against allergens or helminths. In this study, we compared the transcriptomes and proteomes of primary mouse B cells from wild-type and STAT6-deficient mice cultured for 4 d in the presence or absence of IL-4. Microarray analysis revealed that 214 mRNAs were upregulated and 149 were downregulated >3-fold by IL-4 in a STAT6-dependent manner. Across all samples, ∼5000 proteins were identified by label-free quantitative liquid chromatography/mass spectrometry. A total of 149 proteins was found to be differentially expressed >3-fold between IL-4-stimulated wild-type and STAT6-/- B cells (75 upregulated and 74 downregulated). Comparative analysis of the proteome and transcriptome revealed that expression of these proteins was mainly regulated at the transcriptional level, which argues against a major role for posttranscriptional mechanisms that modulate the STAT6-dependent proteome. Nine proteins were selected for confirmation by flow cytometry or Western blot. We show that CD30, CD79b, SLP-76, DEC205, IL-5Rα, STAT5, and Thy1 are induced by IL-4 in a STAT6-dependent manner. In contrast, Syk and Fc receptor-like 1 were downregulated. This dataset provides a framework for further functional analysis of newly identified IL-4-regulated proteins in B cells that may contribute to germinal center formation and IgE switching in type 2 immunity.


Knowledge, motivation, and behavior patterns of the general public towards sun protection.
The general public has long been educated about the harms of ultraviolet (UV) exposure and the benefits of photoprotection. Many organizations have worked in close collaboration to deliver the photoprotection message through a variety of programs. Most address the health-related consequences of UV radiation, although appearance-based strategies have also been initiated. As is common with preventative health measures, these intervention efforts have not resulted in meaningful changes in public behavior despite providing seemingly adequate knowledge to do so. Behaviors are often difficult to change on a societal, personal, and biological level. Within these categories, there are unique reasons for the unsatisfactory outcome with photoprotection such as (1) tan is perceived as beautiful, (2) the knowledge conveyed is often superficial, (3) there is a lack of immediate risk/reward, and (4) UV has reinforcing effects on mood. We propose that better results could be achieved by creating interventions focused on demographic subsets of the population. Specific techniques include anti-tanning legislature, age or gender-based screening campaigns, anti-tan beauty campaigns, and UV photography. Future photoprotection messages should shift from purely promoting knowledge to inspiring improvements in behavior with targeted strategies.


Histone deacetylase inhibitors--a new tool to treat cancer.
Transcriptional regulation in eukaryotes is a multilevel hierarchical process. It is becoming clear that higher-order chromatin structure, occurring via modifications of histones in their nucleosome structure, plays a crucial role in regulating gene expression, both in normal and pathological states. Deacetylation of histones by histone deacetylases (HDACs) modifies the chromatin from an open gene active euchromatin structure to a closed gene silenced heterochromatin structure. Several cancer promoting mutations and chromosomal translocations result in repression of transcription through abnormal recruitment and activation of HDACs, leading to neoplastic transformation. This is the rationale for the evolvement of HDAC inhibitors as a new class in cancer therapy. Trials have shown anti-proliferation effect of histone deacetylase inhibitors in cell culture, animal models and in human with both hematological and solid tumors. The exact mechanism by which histone deacetylase inhibitors exert their effect is still obscure. Reversal of the alteration in gene expression by fusion transcription factors or overexpressed repressors is just one of several possible explanations. The territory of heterochromatin in the vicinity of the nuclear periphery raised the possibility of involvement of nuclear envelope proteins in the regulation of transcription. Our laboratory is interested in the transcription repression mechanism induced by the nuclear envelope lamina associated polypeptide 2 (LAP2) family of proteins through chromatin modification. Here, we will describe the structure of the nucleosome, review regulation of gene expression by acetylation of histones and give an update on the current phase I and phase II clinical trials with histone deacetylase inhibitors.


[Spondyloarthropathies--clinical evaluation and physical therapy].
Spondyloarthropathy is a group of chronic autoimmune disorders including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, acute anterior uveitis and undifferentiated spondyloarthropathies. The spondyloarthropathies share common clinical, radiological, and genetic features that are clearly distinct from other inflammatory rheumatic diseases. The major goal in the management of patients with rheumatic disorders is to control or cure the disease and to preserve and control function and health status. To measure treatments' efficacy standardized assessment of organ morphology, function, and of health status are required. The instruments for measuring health status or quality of life cover a variety of dimensions of health, including physical, social, and emotional functioning. Measurements used to evaluate the efficacy of treatments in ankylosing spondylitis include spinal and chest movement, duration and severity of morning stiffness, and quality of sleep. Health status indices such as the HAQ or AIMS are not readily applicable to spondyloarthropaties. It is reason to use some others: 1. Functional status measure S-HAQ for patients with spondylitis by adding five items to the HAQ, to cover the activities identified as most problematic; 2. Functional index for the assessment of ankylosing spondylitis (Dougados Functional Index - DFI) - it is valid and reliable and shows sufficient responsiveness; S-HAQ appears at least as sensitive to change as the Dougados Index; 3. The Leeds Disability Questionnaire assesses disability in ankylosing spondylitis, inquiring about four areas of function: mobility, bending down, reaching up and neck movements, and postures; 4. The Bath Ankylosing Spondylitis Functional Index (BASFI) 10 item self-administered questionnaire to assess function and activities of daily living in patients with ankylosing spondylitis. Physical therapy is one of the most important way to restore function and health status in patients with spondyloarthropathies, esspecially individual kinesitherapy. We use and many other procedures combine them with kinesitherapy (ultrasound, cryotherapy, electrotherapy, laser ...).


An observational, sequential analysis of the relationship between local economic distress and inequities in health outcomes, clinical care, health behaviors, and social determinants of health.
Socioeconomic status has long been associated with population health and health outcomes. While ameliorating social determinants of health may improve health, identifying and targeting areas where feasible interventions are most needed would help improve health equity. We sought to identify inequities in health and social determinants of health (SDOH) associated with local economic distress at the county-level. For 3,131 counties in the 50 US states and Washington, DC (wherein approximately 325,711,203 people lived in 2019), we conducted a retrospective analysis of county-level data collected from County Health Rankings in two periods (centering around 2015 and 2019). We used ANOVA to compare thirty-three measures across five health and SDOH domains (Health Outcomes, Clinical Care, Health Behaviors, Physical Environment, and Social and Economic Factors) that were available in both periods, changes in measures between periods, and ratios of measures for the least to most prosperous counties across county-level prosperity quintiles, based on the Economic Innovation Group's 2015-2019 Distressed Community Index Scores. With seven exceptions, in both periods, we found a worsening of values with each progression from more to less prosperous counties, with least prosperous counties having the worst values (ANOVA p < 0.001 for all measures). Between 2015 and 2019, all except six measures progressively worsened when comparing higher to lower prosperity quintiles, and gaps between the least and most prosperous counties generally widened. In the late 2010s, the least prosperous US counties overwhelmingly had worse values in measures of Health Outcomes, Clinical Care, Health Behaviors, the Physical Environment, and Social and Economic Factors than more prosperous counties. Between 2015 and 2019, for most measures, inequities between the least and most prosperous counties widened. Our findings suggest that local economic prosperity may serve as a proxy for health and SDOH status of the community. Policymakers and leaders in public and private sectors might use long-term, targeted economic stimuli in low prosperity counties to generate local, community health benefits for vulnerable populations. Doing so could sustainably improve health; not doing so will continue to generate poor health outcomes and ever-widening economic disparities.


Sense and Sensitivity: A Response to the Commentary by Keller et al. (2018).
This reply to the commentary by Keller et al. (2018) on the article "Universality Without Uniformity: A Culturally Inclusive Approach to Sensitive Responsiveness in Infant Caregiving" (Mesman et al., ) highlights key points of agreement emphasizing the sense of investing in synergies across research traditions. These include the importance of distinguishing between different parenting constructs, the need for more studies to test the presented theoretical assumptions, and the value of examining multiple caregiver sensitivity in relation to infants' developing membership of a community. The only point of disagreement reflects the rigidity versus flexibility of the sensitivity construct. This reply argues that it is exactly the versatility of the sensitivity construct that makes it a valuable building block for bridges between fields.


MicroRNA-4458 suppresses migration and epithelial-mesenchymal transition via targeting HMGA1 in non-small-cell lung cancer cells.
Increasing studies have shown that microRNA-4458 (miR-4458) is associated with human cancer progression. However, the molecular mechanism of miR-4458 in non-small-cell lung cancer (NSCLC) remains largely unknown. This study aims to reveal the biological function of miR-4458 in NSCLC. The expression of miR-4458 in NSCLC cells was evaluated by qRT-PCR. Cell proliferation and migration assay were carried out in vitro after transfection. A luciferase reporter and Western blot assay were performed to identify the functional target of miR-4458. The study indicated that miR-4458 was markedly downregulated in NSCLC cells. Overexpression of miR-4458 strongly reduced the proliferation and migration in NSCLC cell lines. In addition, miR-4458 inhibited the progression of migration and epithelial-mesenchymal transition (EMT) through the PI3K/AKT pathway. Luciferase report assay demonstrated that HMGA1 was a target gene for miR-4458. The results indicate that miR-4458 participated in the process of migration and EMT via directly targeting HMGA1 and miR-4458 might be a potential novel therapeutic target in NSCLC.


Anesthesia and subarachnoid intracranial pressure.
Intracranial pressure (ICP) was continuously monitored by the Richmond technic of Vries and Becker in 17 patients undergoing elective craniotomy. This method entails the placement, underlocal anesthesia, of a hollow screw through the cranium into the subarachnoid space. The screw was connected to a Statham P23Db pressure transducer with heavy vinyl tubing and with pressures recorded on a Beckman Dynograph. The effects of 3 anesthetic technice-halothane, enflurane, and nitrous oxide-narcotic-relaxant-on ICP during induction and maintenance were compared with preinduction control pressures. Control ICP in awake, lightly premedicated patients was 15 plus or minus 10 torr. Mask inductions with halothane and enflurane consistently caused significant increases in ICP from preinduction levels in the absence of excitement or airway obstruction. Induction with nitrous oxide-narcotic-relaxant did not increase ICP. Decreases in ICP following barbiturate administration were noted. Addition of halothane and enflurane to the inspired mixture of patients controlled and hyperventilated with nitrous oxide and oxygen caused consistent increases in ICP. With control hyperventilation (Paco2 25 plus or minus 5 torr), the ICP did not return toward preinduction values within 5 minutes with enflurane and halothane.


Content mazes and filled pauses in narrative language samples of children with specific language impairment.
Linguistic nonfluencies known as mazes (filled pauses, repetitions, revisions, and abandoned utterances) have been used to draw inferences about processing difficulties associated with the production of language. In children with normal language development (NL), maze frequency in general increases with linguistic complexity, being greater in narrative than conversational contexts and in longer utterances. The same tendency has been found for children with specific language impairment (SLI). However, the frequency of mazes produced by children with NL and SLI has not been compared directly at equivalent utterance lengths in narration. This study compared the frequency of filled pauses and content mazes in narrative language samples of school-age children with SLI. The children with SLI used significantly more content mazes than the children with NL, but fewer filled pauses. Unlike content mazes, the frequency of filled pauses remained stable across samples of different utterance lengths among children with SLI. This indicates that filled pauses and content mazes have different origins and should not be analyzed or interpreted in the same way.


Ligand binding to WW tandem domains of YAP2 transcriptional regulator is under negative cooperativity.
YES-associated protein 2 (YAP2) transcriptional regulator drives a multitude of cellular processes, including the newly discovered Hippo tumor suppressor pathway, by virtue of the ability of its WW domains to bind and recruit PPXY-containing ligands to specific subcellular compartments. Herein, we employ an array of biophysical tools to investigate allosteric communication between the WW tandem domains of YAP2. Our data show that the WW tandem domains of YAP2 negatively cooperate when binding to their cognate ligands. Moreover, the molecular origin of such negative cooperativity lies in an unfavorable entropic contribution to the overall free energy relative to ligand binding to isolated WW domains. Consistent with this notion, the WW tandem domains adopt a fixed spatial orientation such that the WW1 domain curves outwards and stacks onto the binding groove of the WW2 domain, thereby sterically hindering ligand binding to both itself and its tandem partner. Although ligand binding to both WW domains disrupts such interdomain stacking interaction, they reorient themselves and adopt an alternative fixed spatial orientation in the liganded state by virtue of their ability to engage laterally so as to allow their binding grooves to point outwards and away from each other. In short, while the ability of WW tandem domains to aid ligand binding is well documented, our demonstration that they may also be subject to negative binding cooperativity represents a paradigm shift in our understanding of the molecular action of this ubiquitous family of protein modules.


Sexual trauma disclosure in clinical settings: addressing diversity.
Although sexual trauma is an experience with wide prevalence, it remains difficult for many individuals to discuss this trauma openly with others. Disclosure of a sexual trauma history to a receptive individual can lead to both emotional and instrumental support. However, a myriad of factors related not only to current circumstances but also to cultural and individual differences determine whether an individual will choose to share his or her trauma history with someone else. Mental health clinicians may be more likely than many other people to be the recipients of a disclosure of sexual trauma. Thus, ensuring that clinicians show sensitivity to the role that diverse demographic and cultural factors can play in the process of disclosure is important to facilitating a thoughtful and productive response to such an event. The current article reviews a segment of the literature on disclosure of sexual assault and focuses on selected diversity domains (i.e., nonheterosexual orientation, age, gender, and race) that may impact the disclosure of sexual assault. Practical suggestions are proposed to assist clinicians in assessing sexual trauma and facilitating disclosure in a culturally competent manner.


A simulation study of CS2 solutions in two related ionic liquids with dications and monocations.
Atomistic simulations of solutions of CS2 in an ionic liquid, [ C 8 ( C 1 im ) 2 ] [ NTf 2 ] 2 , with a divalent cation and in the corresponding ionic liquid with a monovalent cation, [C4C1im][NTf2], were carried out. The low-frequency librational density of states of the CS2 was of particular interest in view of recent optical heterodyne-detected Raman-induced Kerr effect spectroscopy (OHD-RIKES). Compared to the monocation ionic liquid, the maximum shifts to higher frequencies in the dication ionic liquid under ambient conditions, but was found to be significantly pressure-dependent. CS2 molecules lie above and below the plane of the imidazolium rings and found to be close to the butyl tails of the monocation. The diffusion rates and embedding energies of solvent ions and CS2 in the two ionic liquids were measured.


Separation of Excess Fluoride from Water Using Amorphous and Crystalline AlOOH Adsorbents.
Aluminum hydroxide is an effective defluoridation adsorbent; however, the poor defluoridation performance limits its wide application. In this work, amorphous and crystalline AlOOH adsorbents are synthesized through hydrolysis of Al salts, and their defluoridation performances are evaluated in terms of adsorption capacity and rate, sensitivity to pH value, and water quality after defluoridation. The defluoridation performance of AlOOH is closely related to the hydrolysis pH value, but hardly to the type of Al salts. The adsorbent can remove >95% fluoride in the first 2 min and reach adsorption equilibrium within 2 h, and the maximum defluoridation capacity is 41.9 mg/g. Furthermore, the adsorbent exhibits an excellent defluoridation efficiency at a wide pH range of 4.5-10.5. After fluoride removal, the adsorbents prepared at pH values of 6 and 7 exhibit low residual Al concentration. The Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) results confirm that the fluoride removal mechanism is the ligand exchange between fluoride and hydroxyl groups. The excellent defluoridation capacity and low residual Al demonstrate that AlOOH is a potential adsorbent for fluoride separation from water.


Alveolar epithelial regeneration in the aging lung.
Advancing age is the most important risk factor for the development of and mortality from acute and chronic lung diseases, including pneumonia, chronic obstructive pulmonary disease, and pulmonary fibrosis. This risk was manifest during the COVID-19 pandemic, when elderly people were disproportionately affected and died from SARS-CoV-2 pneumonia. However, the recent pandemic also provided lessons on lung resilience. An overwhelming majority of patients with SARS-CoV-2 pneumonia, even those with severe disease, recovered with near-complete restoration of lung architecture and function. These observations are inconsistent with historic views of the lung as a terminally differentiated organ incapable of regeneration. Here, we review emerging hypotheses that explain how the lung repairs itself after injury and why these mechanisms of lung repair fail in some individuals, particularly the elderly.


Ethical issues in nutrition and human immunodeficiency virus.
Ethical dilemmas often arise in the provision of healthcare. In view of the advances in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) medical management since the late 1990s, many of the challenges and ethical dilemmas encountered by healthcare professionals have changed from terminal or end-of-life issues to long-term management issues. This article presents 5 case scenarios on common ethical issues faced by those providing nutrition care to people living with HIV/AIDS and addresses key questions to ask in the ethical deliberative process. Ethical dilemmas surrounding the use of complementary and alternative medicine, providing aggressive nutrition support, dealing with third-party payers for supplement reimbursement, and managing patients with mental health disorders and substance abuse issues are discussed, with possible solutions presented from an ethics point of view.


Program of active aging in a rural Mexican community: a qualitative approach.
Education is one of the key elements in the promotion of a thorough paradigm for active aging. The aim of this study is to analyze factors that contribute the empowerment of older adults in a rural Mexican community and, thus, promote active aging. The study was conducted in a rural Mexican community (Valle del Mezquital), based on an action-research paradigm. One hundred and fifty-five elderly subjects with elementary school education participated in a formal training program promoting gerontological development and health education. Participants in turn became coordinators of mutual-help groups (gerontological nucleus) in Mexico. In-depth interviews were carried out to assess the empowerment after training for active aging. It was found that there was an increasing feeling of empowerment, creativity and self-fulfillment among participants. Among the main factors that positively influenced training of the elderly toward active aging were the teaching of gerontology topics themselves; besides, their motivation, the self-esteem, the increased undertaking of responsibility, the feeling of belonging to the group, and the sharing of information based on personal experience and on gerontological knowledge. The main factors that contribute to empowerment of older adults in a rural Mexican community for participate in active aging programs are the training and teaching of gerontology topics themselves; besides, their interest, experience and involvement.


An electrochemical cell for 2-dimensional surface optical reflectance during anodization and cyclic voltammetry.
We have developed an electrochemical cell for in situ 2-Dimensional Surface Optical Reflectance (2D-SOR) studies during anodization and cyclic voltammetry. The 2D-SOR signal was recorded from electrodes made of polycrystalline Al, Au(111), and Pt(100) single crystals. The changes can be followed at a video rate acquisition frequency of 200 Hz and demonstrate a strong contrast between oxidizing and reducing conditions. Good correlation between the 2D-SOR signal and the anodization conditions or the cyclic voltammetry current is also observed. The power of this approach is discussed, with a focus on applications in various fields of electrochemistry. The combination of 2D-SOR with other techniques, as well as its spatial resolution and sensitivity, has also been discussed.


Benefit sharing and access to essential health care: a happy marriage?
In May 2003, one of the most important benefit sharing agreements to date was signed in South Africa. The South African San Council and the South African Centre for Scientific and Industrial Research agreed to share the benefits derived from genetic research on the Hoodia plant. Payments to the San Council started in 2005 and could reach 1.3 million US Dollars per year for approximately 15 years. Members of the San community in Southern Africa are exposed to serious poverty, resulting in malnutrition and avoidable illnesses. The question we are interested in is: could benefit sharing in compliance with the Convention on Biological Diversity be a partial solution to lack of access to essential health care? In the first part of the paper, we shall briefly introduce the legal background of benefit sharing and the San case. In the second part of the paper, we shall argue that benefit sharing and access to essential health care should not be formally linked. We shall substantiate our claim by introducing practical, normative and so-called 'bigger picture' reasons against the link.


Hyperprolactinemia in men with asthenozoospermia, oligozoospermia, or azoospermia.
The role of serum prolactin (PRL) in male infertility is still unclear. To assess the clinical significance of PRL determination during infertility studies, serum hormones and semen samples from 167 men attending the Andrology Clinic were analyzed, and PRL seric values were correlated with volume, sperm count, motility, viability, and morphology. The range of PRL levels (ng/mL) was 7.3 +/- 2.1 in the control group (n = 46), 13.9 +/- 6.6 in asthenozoospermic (n = 51), 12.6 +/- 7.8 in oligozoospermic (n = 42), and 10.9 +/- 4.8 in azoospermic patients (n = 28). Significantly higher (p < .0001) levels of PRL were found in the men with asthenozoospermia, oligozoospermia, and azoospermia. In the 121 infertile patients with abnormal semen analysis, serum PRL levels were below 14.0 ng/mL (normal mean + 3 SD) in 81 (66.9%) and above this level in 40 (33.1%) cases. Serum FSH and LH concentrations in azoospermic men were significantly higher (p < .0001) when compared with those of the control group, which indicates some disturbance of the spermatogenic process, and estradiol was significantly higher (p < .02) in oligozoospermic patients. No significant differences were found in serum testosterone. Twenty-one patients with idiopathic oligoasthenozoospermia and hyperprolactinemia were treated with 2.5 mg of bromocriptine daily for 6 months, resulting in a nonmeasurable effect on their sperm analysis. In conclusion, two-thirds of patients with oligozoospermia, asthenozoospermia, and azoospermia have normal PRL levels. Infertility in men due to moderate hyperprolactinemia could be associated with these sperm disturbances, but bromocriptine was of no therapeutic utility.


Escherichia coil growth dynamics: A three-pool biochemically based description.
A three-pool growth model of an individual Escherichia coli cell is described herein. The model is based on a previously developed chemically structured complex single cell growth model. The reduction in model complexity and the identification of the essential modes of motion, over the time scale of growth, is achieved by temporal decomposition and analysis of hierarchy in relaxation times. The three-pool model faithfully simulates the changes in cell size, cell shape, cell macromolecular composition, DNA initiation and termination periods, and the dependence of cell growth under abiotic glucose limitation. The predictions made by the reduced model compare favorably with both the experimental data and those of the full single cell model (SCM) without any parameter adjustments. The three-pool model has very few significant parameters and has the potential to find immediate practical use in bioreactor design and process control strategies. The model development illustrates the use of modal analysis to yield reduced physiologically realistic dynamic model of complex microbial system such as E. coll.


Neurohumoral blood pressure regulation in lead exposure.
Previous human studies demonstrated that lead exposure may modify the metabolism of catecholamines and of hormones controlled by the hypothalamo-pituitary axis and may affect the kallikrein-kinin system. This paper reports unpublished data on the plasma renin activity of lead-exposed workers; these results are in agreement with those of previous human and experimental studies suggesting that the synthesis or release of renin is increased after short and moderate exposure to inorganic lead and reduced whenever the exposure is prolonged. Previous experimental investigations demonstrated that lead may act on the cardiovascular system, with effects on the renin-angiotensin system, on the reactivity to stimulation of peripheral catecholaminergic receptors, on sympathetic and vagal tone, and on reactivity to the stimulation of baroreceptors. This paper reports the results of a study on male Sprague-Dawley rats that received 0, 15, 30, and 60 micrograms/mL of lead in drinking water for 18 months. Blood pressure was increased in the rats receiving 30 and 60 ppm of lead; cardiac inotropism was augmented only in those receiving the higher dose of the metal, and heart rate was not modified. Cardiovascular responses to agonists indicated that lead exposure affects the renin-angiotensin system and induces sympathetic hyperactivity by acting on central and peripheral sympathetic junctions increasing the responsiveness to stimulation of alpha 2-adrenoreceptors and by increasing the reactivity to stimulation of cardiac and vascular beta-adrenergic and dopaminergic receptors. The cAMP-dependent availability of Ca2+ for contractile mechanisms of the cardiovascular muscle cells was affected by lead.


Wegener's granulomatosis with antiproteinase-3 antibodies occurring after Hodgkin's disease.
We describe the first association between Hodgkin's lymphoma and Wegener's granulomatosis, heralded by renal involvement. A 43-year-old man developed rapidly progressive glomerulonephritis requiring chronic hemodialysis 8 months after remission of Hodgkin's lymphoma. At that moment, no extrarenal involvement was found, despite extensive investigation. Antineutrophil cytoplasm antibodies were positive, without specificity for proteinase-3 or myeloperoxydase. Six months after beginning hemodialysis, multiple pulmonary nodules appeared, along with rapid clinical worsening. A surgical biopsy was performed which disclosed a giant cell granuloma. Antimyeloperoxydase antibodies remained negative, whereas proteinase-3 antibodies became positive. Wegener's granulomatosis was diagnosed and treatment with cyclophosphamide and steroids was started. Clinical and radiological improvement occurred promptly. Eleven months after treatment, both Wegener's disease and Hodgkin's lymphoma remained in remission.


Human papillomavirus DNA is found in the vas deferens.
The role of the male reproductive tract as a reservoir for human papillomavirus (HPV) infection is poorly understood. To analyze the presence of HPV DNA, 27 samples, comprising postvasectomy semen samples and pre- and postejaculation urine samples, were obtained from 18 men recalled for follow-up. HPV DNA was analyzed by nested polymerase chain reaction, confirmed with Southern blot hybridization, cloned, and sequenced. Multiple HPV types were found in different DNA samples of the same men. Five (18.5%) of 27 vas deferens samples contained HPV type 6, 11, or 16. Five (27.8%) of 18 seminal plasma samples (secretions without semen cells) were HPV DNA positive. None of the men had both vas deferens and semen plasma samples HPV positive. Several HPV types can be detected in the male reproductive tract at the same time. This is the first report to show HPV DNA in the vas deferens.


Effect of tailoring π-linkers with extended conjugation on the SJ-IC molecule for achieving high VOC and improved charge mobility towards enhanced photovoltaic applications.
The problem of low efficiency of organic solar cells can be solved by improving the charge mobility and open circuit voltage of these cells. The current research aims to present the role of π-linkers, having extended conjugation, between the donor and acceptor moieties of indacenodithiophene core-based A-π-D-π-A type SJ-IC molecule to improve the photovoltaic performance of pre-existing SJ-IC. Several crucial photovoltaic parameters of SJ-IC and seven newly proposed molecules were studied using density functional theory. Surprisingly, this theoretical framework manifested that the tailoring of SJ-IC by replacing its π-linker with linkers having extended π-conjugation gives a redshift in maximum absorption coefficient in the range of 731.69-1112.86 nm in a solvent. In addition, newly designed molecules exhibited significantly narrower bandgaps (ranging from 1.33 eV to 1.93 eV) than SJ-IC having a bandgap of 2.01 eV. Similarly, newly designed molecules show significantly less excitation energy in gaseous and solvent phases than SJ-IC. Furthermore, the reorganization energies of DL1-DL7 are much lower than that of SJ-IC, indicating high charge mobility in these molecules. DL6 and DL7 have shown considerably improved open circuit voltage (VOC), reaching 1.49 eV and 1.48 eV, respectively. Thus, the modification strategy employed herein has been fruitful with productive effects, including better tuning of the energy levels, lower bandgaps, broader absorption, improved charge mobility, and increased VOC. Based on these results, it can be suggested that these newly presented molecules can be considered for practical applications in the future.


Interaction and transference.
The author begins by pointing out that, whereas in classical psychoanalysis the present was seen as an instrument affording access to the past, reconstruction of which would free the patient from the repetition compulsion, nowadays the past is regarded more as a means of throwing light on the present and the emphasis has shifted to the here and now, the unconscious meanings of which are elucidated by the analyst's careful monitoring of his own mental states. In transference analysis in the here and now, what is analysed today, in the current revised conception of the analyst's role, is the interaction between patient and analyst. The author notes that the concept of interaction did not feature in the theory and clinical practice of classical psychoanalysis, according to which the analytic dialogue was supposed to be confined to verbal exchanges. Yet the interactive dimension is of course present in the 'pragmatic' elements of the linguistic communication, whereby patient and analyst influence each other, and can be analysed by constant, spontaneous unconscious-preconscious monitoring of the analytic relationship. Clinical material is presented to illustrate the examination and use of the pragmatic aspects of the patient-analyst interaction. The analyst is shown in the process of analysing the verbal interaction as a background to interpretive activity, which is in this case interpretation of interaction.


Antidepressant usage in schizophrenia.
Depression in schizophrenic patients is common but often untreated. A review of seven recent studies reveals that tricyclic antidepressants (TCAs) can be effective when used in conjunction with neuroleptic medication after the acute psychotic phase has resolved, with only minimal risk of exacerbation of psychotic symptoms. TCAs were not found to be effective against anergy or the "negative symptoms" of schizophrenia, however. The simultaneous use of TCAs and neuroleptics can result in increased blood levels of each, as well as increased risk of anticholinergic side effects. Some promising work in the use of nontricyclic antidepressants in schizophrenia is described.


Two-photon deep-tissue spatially resolved mitochondrial imaging using membrane potential fluorescence fluctuations.
Cell metabolism and viability are directly reflected in their mitochondria. Imaging-based analysis of mitochondrial morphological structure, size and dynamic characteristics can therefore provide critical insight into cell function. However, mitochondria are often very abundant, and due to their close to diffraction-limit size, it is often non-trivial to distinguish a tubular or large mitochondrion from an ensemble of punctate mitochondria. In this paper, we use membrane potential dependent fluorescence fluctuations of individual mitochondria to resolve them using an approach similar to single molecule localization microscopy. We use 2-photon microscopy to image mitochondrial intensity fluctuations at 200 μm deep inside an intact in-vivo mouse soleus muscle. By analyzing the acquired images, we can reconstruct images with an extra layer of information about individual mitochondria, separated from their ensemble. Our analysis shows a factor of 14 improvement in detection of mitochondria.


Mass transport in mammalian lungs: comparative physiology.
Comparative physiology of mass transport of gases in mammalian lungs is surveyed in terms of the use of experimental mammals in inhalation toxicology. Principles of similarity, scaling, and the relationship of metabolism to body size are touched on, with reference to the wide variability among mammals of similar size. Mechanisms that influence the magnitude and distribution of pulmonary ventilation are reviewed, including mechanical differences associated with variation in body size. More systematic and complete descriptions and understanding are needed. Recent advances in the understanding of gas mixing and transport in airways and in the pulmonary acinus have applications in comparative physiology and inhalation toxicology that are worth exploring.


Cytoprotective propensity of green tea polyphenols against citrinin-induced skeletal-myotube damage in C2C12 cells.
The mycotoxin citrinin, is produced by several species of Penicillium, Aspergillus and Monascus, and is capable of inducing cytotoxicity, oxidative stress and apoptosis. The aim of the present study was to investigate the effect of citrinin in mouse skeletal muscle cells (C2C12) and to overcome the cellular adverse effects by supplementing green tea extract (GTE) rich in polyphenols. C2C12 myoblasts were differentiated to myotubes and were exposed to citrinin in a dose dependent manner (0-100 µM) for 24 h and IC50 value was found to be 100 µM that resulted in decreased cell viability, increased LDH leakage and compromised membrane integrity. Mitochondrial membrane potential loss, increased accumulation of intracellular ROS and sub G1 phase of cell cycle was observed. To ameliorate the cytotoxic effects of CTN, C2C12 cells were pretreated with GTE (20, 40, 80 µg/ml) for 2 h followed by citrinin (100 µM) treatment for 24 h. GTE pretreatment combated citrinin-induced cytotoxicity and oxidative stress. GTE at 40 and 80 µg/ml significantly promoted cell survival and upregulated antioxidant enzyme activities (CAT, SOD, GPx) and endogenous antioxidant GSH, while the gene and protein expression levels were significantly restored through its effective antioxidant mechanism. Present study results suggested the antioxidant properties of GTE as a herbal source in ameliorating the citrinin-induced oxidative stress.


Eye-Tracking as a Tool to Evaluate Functional Ability in Everyday Tasks in Glaucoma.
To date, few studies have investigated the eye movement patterns of individuals with glaucoma while they undertake everyday tasks in real-world settings. While some of these studies have reported possible compensatory gaze patterns in those with glaucoma who demonstrated good task performance despite their visual field loss, little is known about the complex interaction between field loss and visual scanning strategies and the impact on task performance and, consequently, on quality of life. We review existing approaches that have quantified the effect of glaucomatous visual field defects on the ability to undertake everyday activities through the use of eye movement analysis. Furthermore, we discuss current developments in eye-tracking technology and the potential for combining eye-tracking with virtual reality and advanced analytical approaches. Recent technological developments suggest that systems based on eye-tracking have the potential to assist individuals with glaucomatous loss to maintain or even improve their performance on everyday tasks and hence enhance their long-term quality of life. We discuss novel approaches for studying the visual search behavior of individuals with glaucoma that have the potential to assist individuals with glaucoma, through the use of personalized programs that take into consideration the individual characteristics of their remaining visual field and visual search behavior.


[EVALUATION OF GENOMIC PARAMETERS IN DUCTAL BREAST CANCER PATIENTS AND THE ABILITY OF IT'S CORRECTION].
The level of DNA single strand breaks, chromosomal abnormalities and sister chromatid exchanges and the possibility of its normalization with oligopeptide bioregulator Livagen and cobalt ions in the lymphocyte culture from patients with breast cancer have been studied. The results show that the genome of ductal breast cancer patients is characterized by the high density of DNA single strand breaks, high frequency of chromosomal abnormalities and increased levels of chromatin condensation. The usage of Livagen and cobalt in the form of modifying agents has a protective effect by all studied parameters. The obtained results allow us to conclude that research of lymphocytes of ductal breast cancer patients using the analysis conducted by us, can be useful in assessing the therapeutic effect in the treatment of breast cancer patients.


Chloroform deposition in renal cyst fluid of hemodialysis patients with renal cystic disorders.
Chronic exposure to chloroform (CHCl3) induces renal neoplasms in rodents and may be carcinogenic in humans, but studies on chronic CHCl3 deposition in the human body have not been performed. In this study, we examined 27 hemodialysis patients with renal cystic diseases including acquired cystic disease of the kidney (ACDK) accompanied by renal tumors at high frequency. Intracystic and serum CHCl3 concentrations were determined using a headspace gas chromatography/mass spectrometry analysis. CHCl3 was not detected in the serum in any cases, but levels ranging from <0.1 to 0.659 mg/L were found in the cyst fluid in most cases, including patients with ACDK and autosomal dominant polycystic kidney disease. Because intracystic CHCl3 deposition was not confined to ACDK cases, we were unable to evaluate the relationship between CHCl3 accumulation and carcinogenesis in ACDK. However, our results suggest that compounds such as CHCl3 accumulate in renal cyst fluid in hemodialysis patients with renal cystic diseases.


Anthem's P4P program wins Eisenberg award.
Program participants achieve impressive improvement in door-to-balloon time and complication rates. Collaborative effort involves hospitals from the very beginning. Results of participating hospitals are publicly reported.


Evidence of limited capacity and noise reduction with single-element displays in the location-cuing paradigm.
Precuing a location facilitates accuracy of identification of a target at that location and reduces noise from other nontarget characters in a multicharacter field. In 5 experiments, evidence for facilitation included higher accuracy with long precue-target intervals than with short intervals and higher accuracy when a precue indicated the correct location than with short intervals and higher accuracy when a precue indicated the correct location than when it indicated the wrong location. These results were found for each target-mask condition used (1 target with 1 mask, 1 target with 4 masks, or 1 target and 3 nontargets with 4 masks) in experienced and inexperienced observers. Evidence for noise reduction was found because accuracy was higher in the 1 target-1 mask condition than in the other conditions on correctly cued trials with short-cue-target intervals and on incorrectly cued trials. Data are related to methodological factors that are important to obtaining these effects and to capacity and noise reduction models.


Expression of chicken linker histones in E. coli: sources of problems and methods for overcoming some of the difficulties.
Expression of histones in Escherichia coli is important in structural studies on chromatin, because it allows isotopic labeling such as deuteration and replacement of methionines with selenomethionine as well as expression of specific domains of histones. We show that full-length H5 cannot be expressed in E. coli. We have determined that the problem is translational rather than transcriptional. Pulse-labeling studies show that protein turnover is not the reason for lack of accumulation. On dissecting the gene, we find that the problem lies in expressing the highly charged C-terminal tail of H5. We can make progressively increasing amounts of the tail, but at the point where over two-thirds of this region is transcribed, the protein ceases to be made. Surprisingly, full-length H1 is made. In vitro studies show that the H5 gene can be translated in a rabbit reticulocyte system but not in an E. coli system, suggesting that there may be a difference in the ability of eukaryotic and prokaryotic ribosomes to translate this message. The expression of the globular domains of H5 and H1 posed a different problem. There was little or no expression of some of the constructs, even though they were fragments of larger constructs that were well made. Replacement of the first five codons downstream of the initiating ATG codon with those optimized for E. coli, and which were AT rich, restored expression. This may have general implications for expression of eukaryotic proteins in E. coli.


Talker variability in word recognition under cochlear implant simulation: Does talker gender matter?
Normal-hearing listeners are less accurate and slower to recognize words with trial-to-trial talker changes compared to a repeating talker. Cochlear implant (CI) users demonstrate poor discrimination of same-gender talkers and, to a lesser extent, different-gender talkers, which could affect word recognition. The effects of talker voice differences on word recognition were investigated using acoustic noise-vocoder simulations of CI hearing. Word recognition accuracy was lower for multiple female and male talkers, compared to multiple female talkers or a single talker. Results suggest that talker variability has a detrimental effect on word recognition accuracy under CI simulation, but only with different-gender talkers.


Dhis and Dhāt: Evidence of Semen Retention Syndrome Amongst White Britons.
The uncritical application of western psychiatric concepts in non-western societies resulting in culturally invalid psychiatric syndromes, have been extensively documented. Such instances are considered 'category errors'. In contrast, 'reverse category errors' although theoretically postulated, have never been empirically demonstrated. Diagnostic criteria of an established South Asian culture specific neurosis, Dhāt syndrome, were deployed by a psychiatrist of South Asian origin, amongst 47 white Britons in London, UK, presenting for the first time with a clinic diagnosis of ICD-9 Depressive Neurosis (Dysthymic Disroder, ICD-11). The proceedure yielded a new disorder, Semen Retention Syndrome. Based on narrative accounts and quantitative scores on the Hamilton Depression Rating Scale, the evidence suggests that a significant subset of white British subjects diagnosed with Dysthymic Disorder, may in fact be expressing a psychological variation of a previously unknown local White British somatisation phenomena labelled Semen Retention Syndrome. Anxiety and depressive symptoms presented by this subset of subjects were primarily attributed to a core irrational belief and a cognitive error centered around misunderstood concepts of semen physiology. Consequently, the undue focus on mood idioms by both white British patients and their health professionals, leads to a mistaken diagnosis of Mood Disorder, and results in incorrect treatment. The implications of this ethnocentric mode of reasoning raises concerns about existing concepts in psychiatric phenomenology and for official international diagnostic classificatory systems. The paper concludes by arguing that category errors in both directions are instances of cultural iatrogenesis, and underscore the importance of a culturally valid psychiatry.


Evaluation of delayed type immune reactivity in patients with acne vulgaris.
The delayed-type immune reactivities of 39 patients suffering from moderate to severe papulopustular or nodulo-cystic forms of Acne vulgaris were compared with healthy acne-free controls. In vivo reactivity was assessed by skin testing with four common recall antigens. In vitro the afferent arm of the immune system was assayed by antigen and mitogen simulated lymphocyte transformation and the efferent arm by granulocyte random migration and by granulocyte responsiveness to a standard migration inhibitory lymphokine preparation. Spontaneous lymphocyte transformations were also evaluated. In acne patients the skin test reactivities were in general only slightly decreased. Their lymphocytes showed relatively normal responses to mitogen stimulation, but antigen responsiveness was significantly diminished. Furthermore the patients' lymphocytes showed increased spontaneous transformation. All these changes correlated, to some extent, with the severity of the disease. The granulocytes of acne patients showed increased random migration, of borderline significance, but the granulocyte responses to the lymphokine preparation were completely normal. The results suggest that immunologic abnormalities are mild and probably secondary to the inflammatory process.


NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.
The NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic focus primarily on assessment of pathogenic/likely pathogenic (P/LP) variants associated with increased risk of breast, ovarian, pancreatic, and prostate cancer, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, and recommended approaches to genetic counseling/testing and care strategies in individuals with these P/LP variants. These NCCN Guidelines Insights summarize important updates regarding: (1) a new section for transgender, nonbinary and gender diverse people who have a hereditary predisposition to cancer focused on risk reduction strategies for ovarian cancer, uterine cancer, prostate cancer, and breast cancer; and (2) testing criteria and management associated with TP53 P/LP variants and Li-Fraumeni syndrome.


Conformational and microstructural characteristics of poly(L-lactide) during glass transition and physical aging.
The glass transition and physical aging processes of poly(L-lactide) (PLLA) were studied by variable-temperature Fourier transform infrared (FTIR) spectroscopy and (13)C solid-state NMR spectroscopy. The glass transition temperature (T(g)) of PLLA can be well determined from the temperature-dependent FTIR intensity. Nearby T(g), a distinct change in the slope of spectral intensity versus temperature plot is detected. FTIR results suggest that the energy-favorable gauche-trans (gt) conformers rearrange into the less energy-favorable gauche-gauche (gg) counterparts with heating over the glass transition region, which becomes more distinct at temperature above T(g). Besides, the 1267 cm(-1) band, which shows different trends of variation from the other bands upon heating, was assigned to be more sensitive to the nu(as)(C-O-C)+delta(CH) vibration mode of the less energy-favorable gg conformers in PLLA. By comparing the FTIR spectra of the aged and deaged PLLA, it was demonstrated that the rearrangement from the high- to low-energy conformers, i.e., gg to gt, occurs with physical aging. (13)C spin-lattice relaxation measurements indicate that the relaxation rate distribution broadens with aging, which agrees with the previous suggestion that the locally ordered domains are formed during physical aging. Because of the larger variation in the conformational state and microstructure, the FTIR intensities vary much more abruptly for the aged sample with heating to nearby T(g).


The multiple vitamin status of Chinese pregnant women with anemia and nonanemia in the last trimester.
Iron-deficiency or anemia in pregnancy is a major public health problem in China. This cross-sectional study was carried out to observe the association between iron status and multiple vitamin levels of Chinese pregnant women in the third trimester. We measured iron, ascorbic acid, retinol, folate and vitamin B12 in serum, and riboflavin in urine specimens of 1,163 pregnant women in four sites throughout rural and city areas in China. Based on hemoglobin concentrations (Hb), the subjects were divided into an anemia group with Hb < 110 g/L or Hb < or = 100 g/L as severe anemia group, and nonanemia group with Hb > or = 110 g/L. Results showed that 41.58% of the population with serum iron < 700 microg/L and 51.04% of the population with ferritin < 12 microg/L in the anemia group, percentages that were much higher than those in the nonanemia group. Relationships between five vitamins and hemoglobin concentrations of all subjects were observed. There was a lower level of serum ascorbic acid (291.05 microg/dL) in the Hb < or = 100 g/L group than in the Hb > or = 120 g/L group (487.79 microg/dL) (p < 0.001). Serum levels of vitamin B12 and folate were 445.67 pg/mL and 5.94 ng/mL in the Hb < or = 100 g/L group, whose levels were much lower than the levels of 502.01 pg/mL (p < 0.012) and 8.07 ng/mL (p < 0.010) respectively in the Hb > or = 120 g/L group. Further, cross-sectional analysis showed positive correlations between abnormal hematological results and prevalences of vitamin deficiencies. The subjects with iron-deficiency anemia had much higher rates of vitamin C, folate and vitamin B12 deficiencies than those in the nonanemic subjects, and especially in the deficient rates of ascorbic acid and folate in the anemia (Hb < 110 g/L) group, which reached 64.04% and 22.70% respectively. Moreover, we observed that the decreasing trends of hemoglobin concentrations were accompanied by the decreases of serum levels of vitamin A, ascorbic acid, folate and vitamin B12. In conclusion, multiple vitamin deficiencies, especially ascorbic acid, retinol and folic acid, may be associated with anemia or iron deficiency in pregnant women in the last trimester. The study suggested that anemic pregnant women in China should be supplemented with iron and multiple vitamins simultaneously.


Magnetic resonance imaging and computed tomography of hyperacute spinal epidural hematoma.
The authors report a case of hyperacute spinal epidural hematoma, an uncommon condition, imaged by both magnetic resonance imaging and computed tomography. The relative specificity of these two imaging methods for this abnormality is discussed, and recommendations for emergent imaging in this setting are given.


[Epilepsy in the elderly].
Diagnostic work-up and treatment of patients who have developed epilepsy after the age of 65 can both be difficult. Epilepsy is one of the most common neurological conditions in the elderly, and the incidence of de novo geriatric epilepsy is rising. The aim of this review is to provide guidance on the management of epilepsy in this patient group. The review is based on a discretionary selection of original articles and reviews found in PubMed using the search term combination 'epilepsy' and 'elderly', and the authors' personal experience. The seizures, which are most commonly of the focal type, are not infrequently overlooked or misdiagnosed. Cerebrovascular disease is the underlying cause of about half of the cases. When selecting an anticonvulsant, it is important to take age-related physiological changes and comorbidities into consideration. Because elderly patients have a narrower therapeutic window than younger persons and greater susceptibility to cognitive and other side effects, a low starting dose and slower dose titration are particularly important. The results of studies of young epilepsy patients cannot be extrapolated to apply to elderly patients. More studies directly targeting this patient population are therefore needed. As a general rule, we do not recommend starting on enzyme-inducing drugs such as phenytoin, phenobarbital and carbamazepine, partly because of their high interaction potential.


A possible mechanism of the nucleus accumbens and ventral pallidum 5-HT1B receptors underlying the antidepressant action of ketamine: a PET study with macaques.
Ketamine is a unique anesthetic reagent known to produce various psychotic symptoms. Ketamine has recently been reported to elicit a long-lasting antidepressant effect in patients with major depression. Although recent studies provide insight into the molecular mechanisms of the effects of ketamine, the antidepressant mechanism has not been fully elucidated. To understand the involvement of the brain serotonergic system in the actions of ketamine, we performed a positron emission tomography (PET) study on non-human primates. Four rhesus monkeys underwent PET studies with two serotonin (5-HT)-related PET radioligands, [(11)C]AZ10419369 and [(11)C]DASB, which are highly selective for the 5-HT1B receptor and serotonin transporter (SERT), respectively. Voxel-based analysis using standardized brain images revealed that ketamine administration significantly increased 5-HT1B receptor binding in the nucleus accumbens and ventral pallidum, whereas it significantly reduced SERT binding in these brain regions. Fenfluramine, a 5-HT releaser, significantly decreased 5-HT1B receptor binding, but no additional effect was observed when it was administered with ketamine. Furthermore, pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX), a potent antagonist of the glutamate α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor, blocked the action of ketamine on the 5-HT1B receptor but not SERT binding. This indicates the involvement of AMPA receptor activation in ketamine-induced alterations of 5-HT1B receptor binding. Because NBQX is known to block the antidepressant effect of ketamine in rodents, alterations in the serotonergic neurotransmission, particularly upregulation of postsynaptic 5-HT1B receptors in the nucleus accumbens and ventral pallidum may be critically involved in the antidepressant action of ketamine.


Review of imaging recommendations from Response Assessment in Pediatric Neuro-Oncology (RAPNO).
The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group includes neuroradiologists, neuro-oncologists, neurosurgeons, radiation oncologists, and clinicians in various additional specialties. This review paper will summarize the imaging recommendations from RAPNO for the six RAPNO publications to date covering pediatric low-grade glioma, pediatric high-grade glioma, medulloblastoma and other leptomeningeal seeding tumors, diffuse intrinsic pontine glioma, ependymoma, and craniopharyngioma.


Backward-gazing method for measuring solar concentrators shape errors.
This paper describes a backward-gazing method for measuring the optomechanical errors of solar concentrating surfaces. It makes use of four cameras placed near the solar receiver and simultaneously recording images of the sun reflected by the optical surfaces. Simple data processing then allows reconstructing the slope and shape errors of the surfaces. The originality of the method is enforced by the use of generalized quad-cell formulas and approximate mathematical relations between the slope errors of the mirrors and their reflected wavefront in the case of sun-tracking heliostats at high-incidence angles. Numerical simulations demonstrate that the measurement accuracy is compliant with standard requirements of solar concentrating optics in the presence of noise or calibration errors. The method is suited to fine characterization of the optical and mechanical errors of heliostats and their facets, or to provide better control for real-time sun tracking.


Why Value Framework Assessments Arrive at Different Conclusions: A Multiple Myeloma Case Study.
As the United States transitions from a volume-based health care system to one that rewards value, new frameworks are emerging to help patients, providers, and payers assess the value of medical services and biopharmaceutical products. These value assessment frameworks are intended to support various types of health care decision making. They have the potential to substantially affect patients, whether as tools for shared decision making with their doctors, as an input to care pathways used by providers, or through payer use of the frameworks to make coverage or reimbursement decisions. Prominent among current U.S. value assessment frameworks are those developed by the American Society of Clinical Oncology, the Institute for Clinical and Economic Review, the Memorial Sloan Kettering Cancer Center, and the National Comprehensive Cancer Network. These frameworks generally reflect the interests and expertise of the organizations that developed them. The evidence, methodology, and intended use differ substantially across frameworks, which can lead to highly variable determinations of value for the same treatment therapy. To demonstrate this variability, we explored how these frameworks assess the value of treatment regimens for multiple myeloma. Cross-framework comparisons of multiple myeloma assessments were conducted, and consistency of findings was examined for 3 case studies. A discussion of the analysis explores why different frameworks arrive at different conclusions, whether those differences are cause for concern, and the resulting implications for framework readiness to support health care decision making. Funding for this project was provided by the National Pharmaceutical Council. The authors are employees of the National Pharmaceutical Council, an industry-funded health policy research group that is not involved in lobbying or advocacy. Study concept and design were contributed by Westrich and Dubois, along with Buelt. Westrich took the lead in data collection, along with Dubois, and data interpretation was performed by all the authors. The manuscript was written by Westrich and Buelt, along with Dubois, and revised by all the authors.


Defining and applying the concept of quality of life.
Quality of life has been increasingly used as a scientific concept in literature embracing a wide range of target groups and populations as a whole. Conceptualizations vary, but there is much common ground concerning the domain content embraced by the term. Commentators are also clear that account needs to be taken of both objective life conditions and subjective personal appraisals, and the fact that what is important to each person varies. A synthesis of these perspectives provides a model of quality of life which integrates objective and subjective indicators and individual values across a broad range of life domains. Life domain issues may be categorized within six areas: physical, material, social, productive, emotional and civic well-being. Whatever its precise specification, the model is put forward as a framework for organizing measurement relevant to the quality of life concept rather than as a blueprint for deriving the ultimate single instrument. There is still a need for methodological flexibility. The pre-eminent aim is to relate the fine grain of the experience of individuals with disability to that of the wider world.


Techno-economic Assessment of CO2 Electrolysis: How Interdependencies between Model Variables Propagate Across Different Modeling Scales.
The production of base chemicals by electrochemical conversion of captured CO2 has the potential to close the carbon cycle, thereby contributing to a future energy transition. With the feasibility of low-temperature electrochemical CO2 conversion demonstrated at lab scale, research is shifting toward optimizing electrolyser design and operation for industrial applications, with target values based on techno-economic analysis. However, current techno-economic analyses often neglect experimentally reported interdependencies of key performance variables such as the current density, the faradaic efficiency, and the conversion. Aiming to understand the impact of these interdependencies on the economic outlook, we develop a model capturing mass transfer effects over the channel length for an alkaline, membrane electrolyser. Coupling the channel scale with the higher level process scale and embedding this multiscale model in an economic framework allows us to analyze the economic trade-off between the performance variables. Our analysis shows that the derived target values for the performance variables strongly depend on the interdependencies described in the channel scale model. Our analysis also suggests that economically optimal current densities can be as low as half of the previously reported benchmarks. More generally, our work highlights the need to move toward multiscale models, especially in the field of CO2 electrolysis, to effectively elucidate current bottlenecks in the quest toward economically compelling system designs.


Tobacco control policies of oncology nursing organizations.
Nurses, the largest group of health care professionals, and the policies of nursing organizations, have tremendous potential to promote health and tobacco control. Policies addressing tobacco use have been implemented by a variety of national and international nursing organizations. This article reviews existing tobacco control policies in oncology nursing organizations.


Antineutrophil cytoplasm antibodies in patients with silicosis.
The presence of antineutrophil cytoplasm antibodies (ANCA) was followed up in silicosis with or without renal involvement. From the 68 patients with silicosis, 5 presented renal involvement. Of these 3 showed the presence of pANCA. The other 63 patients without renal involvement presented cANCA only in 2 cases. The control group showed no presence of ANCA. The incidence of ANCA in silicosis with renal involvement was discussed in view of an eventual elucidation of the pathogenesis of this disease, which was frequently associated with autoimmunity diseases.


Influence of Ion Exchange Process Parameters on Broadband Differential Interference.
The paper presents theoretical analyses and experimental investigations of broadband differential interference in planar gradient waveguides made via K+-Na+ ion exchange in BK-7 glass. This technology, due to its large polarimetric dispersion, is especially useful for applications in differential interferometry. We discuss the influence of technological parameters on the operation characteristics of the structure in terms of sensor applications. The refractive index variation in the measured external surroundings affects the modal properties of TE and TM modes and the spectral distribution at the output of the differential interferometer. The optical system described in this work has been designed specifically for use in biological systems where variations in the index of refraction need to be measured.


COVID-19 vaccine hesitancy among marginalized populations in the U.S. and Canada: Protocol for a scoping review.
Despite the development of safe and highly efficacious COVID-19 vaccines, extensive barriers to vaccine deployment and uptake threaten the effectiveness of vaccines in controlling the pandemic. Notably, marginalization produces structural and social inequalities that render certain populations disproportionately vulnerable to COVID-19 incidence, morbidity, and mortality, and less likely to be vaccinated. The purpose of this scoping review is to provide a comprehensive overview of definitions/conceptualizations, elements, and determinants of COVID-19 vaccine hesitancy among marginalized populations in the U.S. and Canada. The proposed scoping review follows the framework outlined by Arksey and O'Malley, and further developed by the Joanna Briggs Institute. It will comply with reporting guidelines from the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The overall research question is: What are the definitions/conceptualizations and factors associated with vaccine hesitancy in the context of COVID-19 vaccines among adults from marginalized populations in the U.S. and Canada. Search strategies will be developed using controlled vocabulary and selected keywords, and customized for relevant databases, in collaboration with a research librarian. The results will be analyzed and synthesized quantitatively (i.e., frequencies) and qualitatively (i.e., thematic analysis) in relation to the research questions, guided by a revised WHO Vaccine Hesitancy Matrix. This scoping review will contribute to honing and advancing the conceptualization of COVID-19 vaccine hesitancy and broader elements and determinants of underutilization of COVID-19 vaccination among marginalized populations, identify evidence gaps, and support recommendations for research and practice moving forward.


Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy.
Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ES-assisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.).


The iron-sulfur protein subunit of succinate dehydrogenase is critical in driving mitochondrial reactive oxygen species generation in Apostichopus japonicus.
Succinate dehydrogenase (SDH) is a mitochondrial enzyme with the unique ability to participate in both the tricarboxylic acid cycle and the electron transport chain to produce reactive oxygen species (ROS). The B subunit of SDH is required for succinate oxidation, which is critical for pro-inflammatory response. In this study, we cloned the iron-sulfur protein subunit of SDH from Apostichopus japonicus (denoted as AjSDHB) via RACE technology and explored its role in the immune system as a response to pathogen infection. The full-length cDNA of AjSDHB was 1442 bp with a complete open reading frame of 858 bp encoding 286 amino acids. Simple modular architecture research tool analysis revealed that AjSDHB contained two conserved domains, including a 2Fe-2S iron-sulfur cluster binding domain and a 4Fe-4S dicluster domain, without a signal peptide. Multiple sequence alignment demonstrated that AjSDHB shared a high degree of structural conservation and sequence identities with other counterparts from invertebrates and vertebrates. Phylogenetic analysis supported the finding that AjSDHB is a new member of the SDHB protein subfamily. Tissue distribution analysis revealed that AjSDHB was expressed in all examined tissues and particularly highly expressed in the muscles. AjSDHB transcripts were markedly induced in coelomocytes both by Vibrio splendidus challenge in vivo and lipopolysaccharide exposure in vitro. Function analysis showed that siRNA-mediated AjSDHB knockdown could substantially reduce the mitochondrial membrane potential (ΔΨm) and further decrease mitochondrial ROS production in A. japonicus coelomocytes. By contrast, AjSDHB overexpression considerably increased ΔΨm and mitochondrial ROS production of A. japonicus coelomocytes. These results supported the idea that AjSDHB is involved in the innate immunity of A. japonicus through its participation in mitochondrial ROS generation.


Kinetic enzymatic method for determining serum creatinine.
Creatinine amidohydrolase is used to measure serum creatinine in a totally enzymatic procedure. Creatine, produced by hydrolysis, is acted upon by creatine kinase, and then by pyruvate kinase and lactate dehydrogenase, to result in a change in absorbance at 340 nm. The amount of creatinine present is related to the rate of change in A340 and is determined from a standard curve. Absorbance and concentration are linearly related to 100 mg/liter and only 250 mul of serum is required. At 1.0 g/liter, heparin, oxalate, citrate, ethylenediaminetetraacetate, ascorbate, or glucose had no significant effect on the accurate determination of creatinine; higher concentrations (30 g/liter) had inhibitory effects on the test. Analytical recovery of creatinine added to either normal or abnormal sera averaged 102%. When results of this procedure and of the standard direct Jaffé test were compared, the latter were significantly higher. Unlike the Jaffé method, the present method of determining creatinine is rapid (about 10 min per test), subject to few or no interfering substances, and requires no serum deproteinization.


A practical approach to advanced terminology services in health information systems.
As the medical informatics field evolves, new functions appear as the focus of interest; a more advanced management of terminology is one of them. Using comprehensive and detailed terminology to represent clinical rules in computer systems, associated with patient information, would allow clinical software to provide patient specific recommendations or alerts. In order to uniform data collection through our HIS, and lay the foundations for future clinical decision support systems, we decided to move from our previous classification-based medical record into new terminology services built around Snomed CT, Spanish Language Version. This paper describes the characteristics of our Terminology Server. The most important achievements of our new terminology system are the centralization of knowledge representation, using a much more detailed terminology system. Clinical data entered at any place of the institution and level of care, is represented uniformly through the whole health information system.