2SLS vs 2SRI: Appropriate Methods for Rare Outcomes and/or Rare Exposures.
Using Monte-Carlo simulations, we compare the two-stage least-squares estimator with two-stage residual inclusion estimators, with varying forms of residuals, to estimate the local average treatment effect parameter for a binary outcome and endogenous binary treatment model in the presence of binary covariates and a binary instrumental variable. We vary the rarity of both the outcome and the treatment and find different estimators to produce the least bias in different settings. We develop guidance for applied researchers and illustrate the utility of this guidance with estimating the effects of long-term care insurance on a variety of binary health care use outcomes among the near-elderly using the Health and Retirement Study. Copyright © 2017 John Wiley & Sons, Ltd.


The impact of prebiotics and salmonellosis on apparent nutrient digestibility and Salmonella typhimurium var. Copenhagen excretion in adult pigeons (Columba livia domestica).
The effects of lactose or fructo-oligosaccharide (FOS) supplementation on the excretion of salmonellae, apparent digestibilities and excreta consistency were studied. Thirty-two male pigeons (Columba livia domestica) were randomly divided into 4 equal groups: 3 of 4 groups were orally infected with 10(9) Salmonella Typhimurium var. Copenhagen, after being offered a drinking water supplement of 2% FOS, 2% lactose, or no supplement, respectively, for 2 wk. Pigeons in the fourth group were not challenged with S. Typhimurium and remained unsupplemented. Initially, FOS increased water intake, resulting in more watery excreta. After infection, supplementation showed no major effects on S. Typhimurium excretion, nitrogen retention, or apparent nutrient digestibilities, although lactose--and to a lesser extent FOS--improved apparent fiber digestibility during recovery from the S. Typhimurium infection. The excreta consistency of all pigeons returned to normal when recovering from the Salmonella infection. In this trial, neither FOS nor lactose was successful in tempering the negative aspects of Salmonella infection in pigeons. Nevertheless, it should be stated that future investigations should clarify the importance of duration and level of prebiotic supplementation and infection level.


Micronuclei and their association with sperm abnormalities, infertility, pregnancy loss, pre-eclampsia and intra-uterine growth restriction in humans.
The micronucleus (MN) assay is increasingly being used to study the association between DNA damage and infertility or pregnancy complications in humans. This review provides a brief overview of the studies published to date. The results of these studies appear to support the plausibility of the following hypotheses: (i) MN in spermatids in semen may be indicative of infertility risk, (ii) MN in peripheral blood lymphocytes in males correlate positively with DNA damage in sperm, (iii) infertile couples exhibit higher frequencies of MN than fertile couples and (iv) an abnormally high frequency of MN in peripheral blood lymphocytes is associated with pregnancy complications including miscarriage, intra-uterine growth restriction and pre-eclampsia. The studies published to date consistently indicate an association of MN in peripheral blood lymphocytes with impaired reproductive capacity. However, the conclusions of these studies, although statistically significant, are limited by small sample sizes and the need for verification in other independent cohorts. In conclusion, more attention should be given to the possibility of using MN assays in peripheral blood lymphocytes and reproductive tissues as a biomarker of risk for infertility and pregnancy complications in humans.


EDEM1 regulates ER-associated degradation by accelerating de-mannosylation of folding-defective polypeptides and by inhibiting their covalent aggregation.
Proteins expressed in the endoplasmic reticulum (ER) are covalently modified by co-translational addition of pre-assembled core glycans (glucose(3)-mannose(9)-N-acetylglucosamine(2)) to asparagines in Asn-X-Ser/Thr motifs. N-Glycan processing is essential for protein quality control in the ER. Cleavages and re-additions of the innermost glucose residue prolong folding attempts in the calnexin cycle. Progressive loss of mannoses is a symptom of long retention in the ER and elicits preparation of terminally misfolded polypeptides for dislocation into the cytosol and proteasome-mediated degradation. The ER stress-induced protein EDEM1 regulates disposal of folding-defective glycoproteins and has been described as a mannose-binding lectin. Here we show that elevation of the intralumenal concentration of EDEM1 accelerates ER-associated degradation (ERAD) by accelerating de-mannosylation of terminally misfolded glycoproteins and by inhibiting formation of covalent aggregates upon release of terminally misfolded ERAD candidates from calnexin. Acceleration of Man(9) or Man(5)N-glycans dismantling upon overexpression was fully blocked by substitution in EDEM1 of one catalytic residue conserved amongst alpha1,2-mannosidases, thus suggesting that EDEM1 is an active mannosidase. This mutation did not affect the chaperone function of EDEM1.


A Smartphone-Based Intervention as an Adjunct to Standard-of-Care Treatment for Schizophrenia: Randomized Controlled Trial.
Antipsychotic medications have limited benefits in schizophrenia, and cognitive behavioral therapy may be beneficial as an adjunct. There may be potential for implementing mobile cognitive behavioral therapy-based treatment for schizophrenia in addition to standard antipsychotic medications. This study aims to determine whether PEAR-004, a smartphone-based investigational digital therapeutic, improves the symptoms of an acute psychotic exacerbation of schizophrenia when it is added to standard treatments. This was a 12-week, multicenter, randomized, sham-controlled, rater-blinded, parallel group proof‑of‑concept study of 112 participants with moderate acute psychotic exacerbation in schizophrenia. This study was conducted in 6 clinical trial research sites in the United States from December 2018 to September 2019. The primary outcome, change in Positive and Negative Syndrome Scale (PANSS) from baseline to week 12 or the last available visit, was analyzed using the mixed-effects regression model for repeated measures, applied to an intent-to-treat sample. The total PANSS scores slightly decreased from baseline over the study period in both groups; the treatment difference at day 85 between PEAR-004 and sham was 2.7 points, in favor of the sham (2-sided P=.09). The secondary scales found no benefit, except for transient improvement in depressive symptoms with PEAR-004. Application engagement was good, and patient and clinical investigator satisfaction was high. No safety concerns were observed. There was some evidence of study site heterogeneity for the onboarding processes and directions on PEAR-004 product use at baseline and throughout the study. However, these differences did not affect the efficacy results. In the largest-to-date randomized, sham-controlled study of a digital therapeutic in schizophrenia, PEAR-004 did not demonstrate an effect on the primary outcome-total PANSS scores-when compared with a nonspecific digital sham control. The secondary and exploratory results also did not demonstrate any notable benefits, except for possible temporary improvement in depressive symptoms. This study provided many useful scientific and operational insights that can be used in the further clinical development of PEAR-004 and other investigational digital therapeutics. ClinicalTrials.gov NCT03751280; https://clinicaltrials.gov/ct2/show/NCT03751280.


[Clinicobiological and morphological profiles of primary sclerosing cholangitis in Tunisia].
Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease strongly associated, in the western series, to inflammatory bowel disease (IBD) and particularly to chronic ulcerative colitis. North African data are rare. aim : To study the epidemiological, clinicobiological and morphological profile of PSC in Tunisia. methods: A retrospective multicenter study extended over a period of 14 years (1995-2009), including all patients suffering from PSC, hospitalized in the four participants departments. We collected epidemiological, clinico-biological, histopathologic and morphological data for each patient. results: We brought together 33 patients (22 men and 11 women), middle aged 44 years. The disease was symptomatic in 73% of cases. Laboratory tests showed cholestasis (100%) associated with hyperbilirubinemia (72%) and a moderate cytolysis (78%). Morphological analysis of bile ducts by cholangioMRI or endoscopic retrograde cholangio-pancreatography objectified diffuse damage of the biliary tract in 61% of cases. Association with IBD was found in 33% of cases (Crohn's Disease: 27%, chronic ulcerative colitis: 6%). An association with autoimmune hepatitis was found in 6% of cases and primary biliary cirrhosis in 3% of cases. Conclusion : PSC is rare in Tunisia and affects men more often than women. The association with IBD is less frequent than in literature. It concerns essentially Crohn's disease. These data require confirmation by prospective multicenter studies.


Synthesis of 1-Amino-2 H-quinolizin-2-one Scaffolds by Tandem Silver Catalysis.
An efficient tandem cycloisomerization-amination reaction catalyzed by silver is described. This rapid and atom-economic reaction delivered 1-amino-2 H-quinolizin-2-one scaffolds in high yields under mild conditions. The reaction could be extended to an asymmetric version albeit with moderate enantioselective excess of the products. In addition, the products can be easily reduced into various azabicycles containing 4-pyridones, which are important building blocks in organic synthesis.


Socializing into a Profession with High Early Turnover: Nursing Students' Expectations for Leader-Member Relationships.
The nursing profession is wrought with high levels of turnover, particularly among new nurses. One reason for this turnover may be explained by a disparity between what new nurses expect in terms of communication from leaders and coworkers and what they realistically receive. This study uses a mixed-methods experimental design to explore young adult nursing students' preferences for manager communication behaviors, how different managerial archetypes influence nursing students' perceptions of their leader, and how personal factors may influence nursing students' preferences for various managerial styles. Findings suggest that new nurses prefer more mentor- and teacher-type managers and that managerial archetypes influence young adult nursing students' perceptions of leader credibility, effectiveness, leader-member exchange, and employee commitment. Furthermore, personal factors such as self-worth and desire for relational communication behaviors influence preferred manager type. Participants' qualitative responses reveal several task and behavioral wants and needs of new nurses. Findings from this study can informatively help to bridge the gap between expectations and reality in the nursing profession, thus addressing a potential reason for consistent turnover.


Activated Microporous Carbon Derived from Almond Shells for High Energy Density Asymmetric Supercapacitors.
Via the activation treatment of carbonized almond shells with HNO3 and KOH, activated microporous carbon (AMC-3 and AMC-2) was successfully synthesized. These two AMC electrodes demonstrate remarkable electrochemical behaviors such as high rate capability, high specific capacitance, and excellent cycle stability when serving as electrodes for supercapacitors. More importantly, through the use of a Zn-Ni-Co ternary oxide (ZNCO) positive electrode and the AMC negative electrode, asymmetric supercapacitors (ASC) were assembled that deliver superior energy density (53.3 Wh kg(-1) at a power density of 1126.1 W kg(-1) for ASC-2 and 53.6 Wh kg(-1) at a power density of 1124.5 W kg(-1) for ASC-3) and excellent stability (82.7% and 83.4% specific capacitance retention for ZNCO//AMC ASC-2 and ZNCO//AMC ASC-3, respectively, after 5000 cycles). Through these two methods, low-cost, renewable, and environmentally friendly electrode materials can be provided for high energy density supercapacitors.


Extremely low-frequency electromagnetic field exposure enhances inflammatory response and inhibits effect of antioxidant in RAW 264.7 cells.
In recent years, there has been a dramatic increase in the number and variety of electronic devices that emit electromagnetic waves. Because people live and work in close proximity to these pieces of electrical equipment, there is growing concern surrounding the destruction of homeostasis by electromagnetic field exposure. In the present study, the effects of 60 Hz 0.8 mT extremely low-frequency electromagnetic fields (ELF-EMF) on a macrophage cell line (RAW 264.7) were examined. Under defined ELF-EMF exposure conditions, the production of nitric oxide and pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were increased in RAW 264.7 cells and the expression of those genes was also upregulated. However, cell proliferation was not altered. Translocation of NF-κB (nuclear factor kappa B), molecules that act downstream of the pro-inflammatory cytokines, were increased to the nucleus under ELF-EMF exposure conditions. In addition, we found that ELF-EMF exposure elevated activation of nuclear factor of activated T cells (NFAT) 2, as well as positively affected the influx of calcium. Furthermore, with both the presence of a potent antioxidant (Resveratrol) and downregulation of the antioxidant-related gene Prx-1 (Peroxiredoxin-1), ELF-EMF was associated with higher inflammatory responses of macrophages. These results suggest that an ELF-EMF amplifies inflammatory responses through enhanced macrophage activation and can decrease the effectiveness of antioxidants. Bioelectromagnetics. 38:374-385, 2017. © 2017 Wiley Periodicals, Inc.


Taxonomic review of the genus Atlantodesmus Hoffman, 2000 (Polydesmida: Chelodesmidae).
The chelodesmid genus Atlantodesmus Hoffman, 2000 is revised and considered a senior synonym of Iemanja Hoffman, 2000. Currently the genus contains five species, all of them are herein redescribed: Atlantodesmus eimeri (Attems, 1898), Atlantodesmus itapurensis (Schubart, 1943), Atlantodesmus pickeli (Schubart, 1946), Atlantodesmus pintoi (Schubart, 1946), and the transferred species from Iemanja, Atlantodesmus teresa (Hoffman, 2000), new combination. The female of Atlantodesmus teresa is described for the first time. Examination of the type material of Leptodesmus buecherli Schubart, 1955 revealed that this species is a junior synonym of A. itapurensis. A key to males and a distribution map of all species are included.


The relative potencies of some substituted salicylic acids as metabolic stimulants in the intact rat.
The effects of eighteen substituted benzoic acids on the rate of oxygen consumption have been studied in rats. 2:3-Dihydroxybenzoic acid, phthalic acid and 6-methylsalicylic acid were, at the doses used, inactive; m- and p-hydroxybenzoic acid, 2:4-, 2:5-, 2:6-, 3:4-, and 3:5-dihydroxybenzoic acid, o-aminobenzoic acid, salicyluric acid, salicylamide and 5-aminosalicylic acid decreased the rate of oxygen consumption. Only salicylic acid and o-, m- and p-cresotic acid (3-, 4- and 5-methylsalicylic acid respectively) increased the rate of oxygen consumption. Molar potency ratios of the cresotic acids as metabolic stimulants relative to salicylic acid were determined; o-cresotic acid was the most powerful with a ratio of 2.61, m- and pcresotic acid had values of 1.78 and 1.89 respectively. Two possible explanations of the higher potencies of the cresotic acids were considered. No difference in the primary action of the drug was established by determining the effect on rate of oxygen consumption of a mixture of o-cresotic and salicylic acids. An alternative possibility was that the rates of detoxication and excretion of the cresotic acids differed among themselves and from salicylic acid. No such differences were found.


Bullous variant of acral erythema due to methotrexate.
Chemotherapy-induced acral erythema is a painful erythema of the palms and soles which occurs following chemotherapy. It is usually seen due to cytarabine, doxorubicin and fluorouracil. We present a 40-year-old male patient, a biopsy proven case of squamous cell carcinoma of the floor of the mouth, who developed a bullous variant of acral erythema after a single intravenous dose of methotrexate. He also had fever, buccal mucositis, leucopenia, thrombocytopenia and hyperpigmented macular rash on the face and upper trunk. The bullous variant of acral erythema due to methotrexate has rarely been reported.


Different genotypes of hepatitis C virus are associated with different severity of chronic liver disease.
The presence of the "Japanese type" NS4 region was investigated in two series of patients (53 from Italy and 58 from Japan) with hepatitis C virus (HCV)-related chronic liver disease. The two populations were homogeneous as regard to age, male/female ratio, histological diagnosis, and serum aminotransferase activities. Genomic amplification was carried out by "nested" polymerase chain reaction (PCR) with a pair of primers synthesized according to the sequence of JK-1 isolated in Japan. The presence of viral replication was confirmed further by PCR amplification of the 5'NC region. The NS4 region of the Japanese strain was detected in 24 sera (45%) from Italy and in 44 (71%) from Japan. NS4-positive patients were significantly older and showed an ALT serum level significantly lower (P < 0.01) than NS4 negative cases in each group. Cirrhosis was significantly (P < 0.0007) more common in NS4-positive than in NS4-negative patients. The HCV genotype was subsequently obtained according to Okamoto. All the NS4-positive patients were infected by Type II, whereas in NS4-negative patients all four genotypes were present though Type II still constituted the majority. Cirrhosis was associated exclusively with Type II both in NS4-positive and -negative subjects. These data indicate that, although the positivity for NS4 "Japanese" region seems to be associated with a more aggressive liver disease, the most prevalent Type II predicts more specifically those who are likely to develop cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)


The influence of agency staffing on quality of care in nursing homes.
Data from a large sample of nursing homes were used to examine the cross-sectional association between use of agency staff, regular staff, and quality. Agency use data came from a survey conducted in 2003 (N=1071 nursing homes). The agency and regular staff measures were for nurse aides, licensed practical nurses, and registered nurses. We used a single quality factor constructed from the 14 quality measures in Nursing Home Compare. More agency nurse aides resulted in a smaller increase in quality, compared to the use of an equivalent number of regular nurse aides. Agency registered nurse staff were associated with better quality factor scores, especially in the presence of high levels of regular licensed practical nurses. Our results have policy and practice implications, the most significant of which is that agency registered nurses may be beneficial in a wide variety of circumstances, whereas agency nurse aides and licensed practical nurses should be used with caution.


Skeletal muscle generated from induced pluripotent stem cells - induction and application.
Human induced pluripotent stem cells (hiPS cells or hiPSCs) can be derived from cells of patients with severe muscle disease. If skeletal muscle induced from patient-iPSCs shows disease-specific phenotypes, it can be useful for studying the disease pathogenesis and for drug development. On the other hand, human iPSCs from healthy donors or hereditary muscle disease-iPSCs whose genomes are edited to express normal protein are expected to be a cell source for cell therapy. Several protocols for the derivation of skeletal muscle from human iPSCs have been reported to allow the development of efficient treatments for devastating muscle diseases. In 2017, the focus of research is shifting to another stage: (1) the establishment of mature myofibers that are suitable for study of the pathogenesis of muscle disease; (2) setting up a high-throughput drug screening system; and (3) the preparation of highly regenerative, non-oncogenic cells in large quantities for cell transplantation, etc.


Effects of Flour and Milling Debris on Efficacy of Beta-Cyfluthrin for Control of Tribolium castaneum (Coleoptera: Tenebrionidae).
Laboratory and field studies were conducted to determine if accumulation of a flour food source or milling debris affected residual efficacy of beta-cyfluthrin for control of Tribolium castaneum (Herbst), the red flour beetle. In the laboratory study, the high label rate of 20 mg active ingredient (AI)/m2 gave effective control for 8 wks, regardless of whether or not the concrete was sealed prior to application or the presence of flour contamination. However, with the low label rate of 10 mg AI/m2, the flour apparently absorbed the insecticide residues from the treated surface, and sealing the concrete did not have a beneficial effect on efficacy. Two field studies with the low label rate were conducted during autumn of 2012 and 2013 and summer of 2013, using only unsealed concrete. Accumulated milling debris caused a reduction in efficacy in the autumn studies, as shown by increased time to 100% knockdown, decreased mortality, and decreased residual efficacy. There was no such corresponding decrease in residual efficacy in the summer study. Overall, results of both studies show that accumulated food and milling debris can absorb residue of beta-cyfluthrin from a treated surface and have a negative impact on residual efficacy, particularly with the low label rate of 10 mg AI/m2.


A monoclonal antibody defining a lymphoma-associated antigen in man.
A monoclonal antibody (Ab 89) was developed against a lymphoma-associated antigen on the tumor cells of a patient (N.B.) with a B cell, poorly differentiated lymphocytic lymphoma (D-PDL). By indirect immunofluorescence, Ab 89 was shown to react only with N.B. lymphoma cells and was unreactive with normal N.B. lymphoid cells, normal fractionated peripheral blood cells, other normal lymphoid tissues, fetal tissues, and non-lymphoid malignant cells. In addition, Ab 89 was unreactive with conventional immunoglobulins, private and public HLA antigens, or Ia-like antigens. More importantly, Ab 89 was reactive with some B cell lymphoid malignancies. Of the 57 B cell lymphomas tested, it was found that Ab 89 reacted with approximately 10% of B cell D-PDL and B cell chronic lymphocytic leukemia (CLL). Of interest was the finding that N.B. serum contained a circulating antigen which could specifically block the reactivity of Ab 89. The data obtained suggests that Ab 89 defines a tumor-associated antigen shared by a unique subgroup of B cell lymphomas. The group of patients reactive with Ab 89 did not fall into any histopathologic classification system. These data support the notion that there is greater heterogeneity of B cell lymphomas than may have been previously recognized.


Gene Mining for Proline Based Signaling Proteins in Cell Wall of Arabidopsis thaliana.
The cell wall (CW) as a first line of defense against biotic and abiotic stresses is of primary importance in plant biology. The proteins associated with cell walls play a significant role in determining a plant's sustainability to adverse environmental conditions. In this work, the genes encoding cell wall proteins (CWPs) in Arabidopsis were identified and functionally classified using geneMANIA and GENEVESTIGATOR with published microarrays data. This yielded 1605 genes, out of which 58 genes encoded proline-rich proteins (PRPs) and glycine-rich proteins (GRPs). Here, we have focused on the cellular compartmentalization, biological processes, and molecular functioning of proline-rich CWPs along with their expression at different plant developmental stages. The mined genes were categorized into five classes on the basis of the type of PRPs encoded in the cell wall of Arabidopsis thaliana. We review the domain structure and function of each class of protein, many with respect to the developmental stages of the plant. We have then used networks, hierarchical clustering and correlations to analyze co-expression, co-localization, genetic, and physical interactions and shared protein domains of these PRPs. This has given us further insight into these functionally important CWPs and identified a number of potentially new cell-wall related proteins in A. thaliana.


Are nerve conduction studies useful for monitoring the adequacy of renal dialysis?
When hemodialysis was first used clinically, a peripheral neuropathy frequently emerged. The discovery that sufficient dialysis time would prevent the emergence of symptomatic neuropathy led to the routine use of nerve conduction studies (NCS) to monitor the "adequacy" of dialysis. Modern dialysis practice has evolved since then, and the patient population is markedly different. This report addresses the question of whether there is evidence to indicate that routine use of NCS is helpful to monitor the adequacy of present-day dialysis. A critical review of the available literature reveals that there is insufficient evidence to allow one to answer the question.


Voluntary Forelimbs Exercise Reduces Immobilization-Induced Mechanical Hyperalgesia in the Rat Hind Paw.
Voluntary exercise is sufficient to protect against neuropathic pain. However, it is unclear whether voluntary exercise reduces immobilization-induced hyperalgesia. We examined the effect of voluntary forelimb exercise on immobilized-induced hyperalgesia in hind paws of rats. Wistar rats were randomly divided into the (1) both hind limbs immobilized group (IM group), (2) immobilization and exercise with nonimmobilized fore limbs group (EX group), and (3) control group. In the IM and EX groups, the bilateral ankle joints of each rat were immobilized in full plantar flexion with a plaster cast for eight weeks. In the EX group, voluntary exercise using nonimmobilized forelimbs in the running wheel was administered during the immobilization period, while hind limbs were kept immobilized (60 min/day, 5 days/week). Mechanical hyperalgesia in the hind paw was measured using a digital von Frey device every week. To investigate the abnormality of primary sensory neurons and central sensitization, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide in the spinal dorsal horn were analyzed by immunohistochemical staining. Immobilization-induced mechanical hyperalgesia was inhibited in the EX group compared to the IM group at three weeks after immobilization. In the EX group, the number of calcitonin gene-related peptide-positive cells in the dorsal root ganglion and the expression level of calcitonin gene-related peptide were significantly decreased compared to those in the IM group. Our results therefore suggest that voluntary forelimb exercise during hind limb immobilization partially reduces immobilization-induced hyperalgesia by suppressing that the plastic changes of the primary sensory nerves that excessively transmit pain and increased responsiveness of nociceptive neurons in the spinal dorsal horn.


Leber's Hereditary Optic Neuropathy in Older Individuals Because of Increased Alcohol Consumption During the COVID-19 Pandemic.
Leber's hereditary optic neuropathy (LHON) is a disorder affecting oxidative phosphorylation in mitochondria. A majority of affected patients are men of 15 to 35 years of age. Phenotypic penetrance of this condition is only 50% in man and 10% in women and increases if the cellular energy demands go up, with the most common risk factors being smoking and alcohol use. Review of clinical features of 3 patients who were diagnosed with LHON in their sixth decade of life after doubling their alcohol intake during the recent COVID-19 pandemic. All 3 patients were older than the age of 50 when they developed severe sequential visual loss. All have at least doubled their alcohol intake for at least 4 weeks preceding visual loss, and 2 who were smokers increased the number of cigarettes consumed daily because of the stress and boredom during the lockdowns triggered by the pandemic. Significant increase in substance abuse in the general population during the recent lockdowns to combat the COVID-19 pandemic is well documented. We report 3 patients older than the age of 50, one of them a woman, who developed severe bilateral visual loss due to LHON after doubling their alcohol consumption and increasing number of cigarettes smoked daily during the pandemic. Clinicians are reminded to consider LHON in the differential diagnosis when encountering older patients with bilateral sequential visual loss and to specifically inquire about alcohol use and cigarette smoking in these patients.


Computational modeling of RNA 3D structure based on experimental data.
RNA molecules are master regulators of cells. They are involved in a variety of molecular processes: they transmit genetic information, sense cellular signals and communicate responses, and even catalyze chemical reactions. As in the case of proteins, RNA function is dictated by its structure and by its ability to adopt different conformations, which in turn is encoded in the sequence. Experimental determination of high-resolution RNA structures is both laborious and difficult, and therefore the majority of known RNAs remain structurally uncharacterized. To address this problem, predictive computational methods were developed based on the accumulated knowledge of RNA structures determined so far, the physical basis of the RNA folding, and taking into account evolutionary considerations, such as conservation of functionally important motifs. However, all theoretical methods suffer from various limitations, and they are generally unable to accurately predict structures for RNA sequences longer than 100-nt residues unless aided by additional experimental data. In this article, we review experimental methods that can generate data usable by computational methods, as well as computational approaches for RNA structure prediction that can utilize data from experimental analyses. We outline methods and data types that can be potentially useful for RNA 3D structure modeling but are not commonly used by the existing software, suggesting directions for future development.


Reported populations of Meloidogyne ethiopica in Europe identified as Meloidogyne luci.
The tropical group of root-knot nematodes (RKN) including Meloidogyne ethiopica and M. luci is a highly polyphagus and damaging group of agricultural pests. M. ethiopica has been detected in several European countries (Slovenia, Italy, Greece) and also in Turkey. However, a description of a new sister species M. luci calls for reclassification of all European and Turkish M. ethiopica populations reported up to date as M. luci. Accurate identification can be accomplished through analysis of the esterase isozyme pattern, which is the most distinguishing character between the two otherwise very similar species. Both species display a three banded esterase pattern where the upper band is slightly shifted between the two species. In addition, molecular characterization of M. ethiopica and M. luci populations revealed that the ITS, SSU, and LSU of the rDNA regions are not appropriate markers for studying relationships among the tropical group of RKNs. However, the COII/lRNA region on mtDNA proved to be very useful for analyzing the phylogenetic relationship of these very closely related species/populations. Mitochondrial sequences with low levels of heteroplasmy allowed clustering of all M. luci populations in a monophyletic clade with a clear separation of this recently described species from M. ethiopica. At the same time, a very close relationship between M. ethiopica and M. luci was confirmed again.


Attenuation of gastric lesions by psychological aspects of aggression in rats.
Rats that fought with each other in response to electric shock showed reduced gastric lesions in comparison with animals that received the same shocks alone so that fighting behavior did not occur. Also, gastric lesions were similarly reduced in animals that fought even though they could not physically contact one another because of a barrier between them, so that the "protective" effect of fighting derived from release of, or display of, fighting behavior and did not require physical combat. A second experiment showed that animals that received shock together but did not engage in fighting behavior showed no reduction of gastric lesions, so that the protective effect of fighting was not an artifact of animals receiving shock together. Possible explanations for why fighting behavior reduces gastric lesions are discussed.


Peptide Receptor-Targeted Fluorescent Probe: Visualization and Discrimination between Chronic and Acute Ulcerative Colitis.
The inflammatory activity of ulcerative colitis plays an important role in the medical treatment. However, accurate and real-time monitoring of the colitis activity with noninvasive bioimaging method is still challenging, especially in distinguishing between chronic and acute colitis. As a good receptor, the oligopeptide transporter (PepT1) is overexpressed in the colonic epithelial cells of chronic ulcerative colitis, which can deliver tripeptide KPV (Lys-Pro-Val, the C-terminal sequence of α-MSH) into cytosol in the intestine. Herein, we report a PepT1 peptide receptor-targeted fluorescent probe, dicyanomethylene-4H-pyran (DCM)-KPV, with the strategy of conjugating the KPV into the DCM chromophore. The diagnostic fluorescent probe bestows a specific receptor-targeted interaction with PepT1 through the KPV moiety, possessing several beneficial characteristics, such as efficient long emission, low photobleaching, negligible cytotoxicity, and high cytocompatibility in living cells. We build the overexpressed PepT1 on the cytomembrane of ulcerative colitis model Caco-2 cell as the efficient receptor to accumulate the targeted tripeptide KPV in the cytoplasm and nucleus. With the co-localization of DCM-KPV and the DNA-specific fluorophore, DAPI, the specifically long emission from chromophore DCM and efficient receptor-targeted peptide KPV, the fluorescent probe of DCM-KPV makes a breakthrough to the direct noninvasive observation of the accumulation in colon inflammation regions via intestinal mucosa, even successfully distinguishing the chronic, acute ulcerative colitis and normal groups. Compared with the traditional unenhanced magnetic resonance imaging and hematoxylin and eosin (H&E) staining, we make full use of exploiting the specific target-receptor interaction between the tripeptide unit, KPV, and the oligopeptide transporter, PepT1, for sensing selectivity. The desirable diagnostic ability of DCM-KPV can guarantee the real-time tracking and visualization of the role of intracellular KPV on ulcerative colitis, which provides an alternative to replace the time-consuming and tissue sampling-invasive H&E staining diagnosis.


Factors affecting graft survival among patients receiving kidneys from live donors: a single-center experience.
The aim of this report is to study the graft and patient survival in a large cohort of recipients with an analysis of factors that may affect the final outcomes. Between March 1976 and March 2008, 1967 consecutive live-donor renal transplants were carried out. Various variables that may have an impact on patients and/or graft survival were studied in two steps. Initially, a univariate analysis was carried out. Thereafter, significant variables were embedded in a stepwise regression analysis. The overall graft survival was 86.7% and 65.5%, at 5 and 10 years, respectively. The projected half-life for grafts was 17.5 years and for patients was 22 years. Five factors had an independent negative impact on graft survival: donor's age, genetic considerations, the type of primary immunosuppression, number of acute rejection episodes, and total steroid dose during the first 3 months after transplantation. Despite refinements in tissue matching techniques and improvements in immunosuppression protocols, an important proportion of grafts is still lost following living donor kidney transplantation, presumably due to chronic allograft nephropathy.


Targeting Rearranged during Transfection in Cancer: A Perspective on Small-Molecule Inhibitors and Their Clinical Development.
Rearranged during transfection (RET) is a receptor tyrosine kinase essential for the normal development and maturation of a diverse range of tissues. Aberrant RET signaling in cancers, due to RET mutations, gene fusions, and overexpression, results in the activation of downstream pathways promoting survival, growth, and metastasis. Pharmacological manipulation of RET is effective in treating RET-driven cancers, and efforts toward developing RET-specific therapies have increased over the last 5 years. In 2020, RET-selective inhibitors pralsetinib and selpercatinib achieved clinical approval, which marked the first approvals for kinase inhibitors specifically developed to target the RET oncoprotein. This Perspective discusses current development and clinical applications for RET precision medicine by providing an overview of the incremental improvement of kinase inhibitors for use in RET-driven malignancies.


Structural complexity of defective-interfering RNAs of Semliki Forest virus as revealed by analysis of complementary DNA.
The 18S defective interfering RNA of Semliki Forest virus has been reverse transcribed to cDNA, which was shown to be heterogeneous by restriction enzyme analysis. After transformation to E.coli, using pBR322 as a vector, two clones, pKTH301 and pKTH309 with inserts of 1.7 kb and 2 kb, were characterized, respectively. The restriction maps of the two clones were different but suggested that both contained repeating units. At the 3' terminus, pKTH301 had preserved 106 nucleotides and pKTH309 102 nucleotides from the 3' end of the viral 42S genome. The conserved 3' terminal sequence was joined to a different sequence in the two clones, and these sequences were not derived from the region coding for the viral structural proteins. The DI RNAs represented by the two clones are generated from the viral 42S RNA by several noncontinuous internal deletions, since the largest colinear regions with 42S RNA are 320 nucleotides in pKTH301, and 430 and 340 nucleotides in pKTH309. All these fragments had unique RNase T1 oligonucleotide fingerprints, suggesting that they were derived from different regions of 42S RNA.


The excessive length of first ray as a risk factor for hallux valgus recurrence.
It is still unknown whether the excessive length of the first ray is a risk factor for hallux valgus recurrence. The purpose of this study is to clarify the relationship between the excessive length of the first ray and the recurrence of hallux valgus. Between 2008 and 2011, a total of 186 feet (left 105, right 81) who underwent chevron osteotomy combined with distal soft tissue procedure in our foot and ankle center were retrospectively reviewed. A postoperative hallux valgus angle(HVA) ≥20° was defined as recurrence. Patients were divided into two groups: recurrence and non-recurrence group. Weight-bearing radiographs were evaluated preoperatively and at the time of last follow-up for both groups. Radiographic parameters including the length of the great toe(P1), the length of the second toe(P2), the length distance between the first and second metatarsal(D), the hallux valgus angle(HVA) were obtained. The excessive length of the first ray(EL) was calculated using the equation of EL = P1-P2-D. A total of 45 patients (24.2%) had hallux valgus recurrence at the time of last follow-up with a mean follow-up of 83.7 ±12.1 months (range, 66-110). The mean postoperative P1 was 5.06±0.39cm for recurrence group and 4.84±0.34cm for no recurrence group(p<0.001). The mean post operative EL was 5.71±5.01mm for recurrence group and 1.61±4.09mm for no recurrence group(p<0.001). The predictive cutoff value of postoperative P1 and postoperative EL for hallux valgus recurrence was 4.9cm [odds ratio (OR) = 8.67, p = 0.03] and 0.4cm (OR = 6.79, p = 0.001) respectively. Significant relationships between postoperative P1, postoperative EL and hallux valgus recurrence were identified according to our radiographic results. A postoperative P1>4.9cm and postoperative EL>0.4cm can be risk factors for hallux valgus recurrence. The appreciation of the excessive length of the first ray prior to surgery may help to improve the surgical outcome.


Plasma clearance of nicotinic acid and rifamycin-SV, and their interaction in Gilbert's syndrome: application of a compartmental model.
The bicompartmental kinetics of nicotinic acid (NA) and rifamycin-SV (R-SV)--2 organic anions that probably share a common hepatic uptake mechanism--were studied in 7 cases of Gilbert's syndrome (GS) and in 7 healthy controls matched for sex and age. In GS the NA and R-SV uptake constants (K21) were significantly decreased. In GS patients, simultaneous loads of NA and R-SV, the latter at increasing doses, produced: 1) a progressive lowering only of R-SV K21; and 2) an increase in R-SV hepatic plasma reflux (K12). Changes in biliary excretion ( Kee ) and hepatocellular pool (Ke) of both NA and R-SV probably depend on the rates of uptake and reflux constants of the two anions. The study of the parameters of compartmental kinetics of NA and R-SV confirms that the two organic anions, which have different metabolic routes and/or a different affinity for intracellular carriers, share common uptake mechanisms.


Morphologic Analysis of Urinary Podocytes in Focal Segmental Glomerulosclerosis.
The development of glomerulosclerosis in FSGS is associated with a reduction in podocyte number in the glomerular capillary tufts. Although it has been reported that the number of urinary podocytes in FSGS exceeds that of minimal-change nephrotic syndrome, the nature of events that promote podocyte detachment in FSGS remains elusive. In this study, we provide detailed, morphologic analysis of the urinary podocytes found in FSGS by examining the size of the urinary podocytes from patients with FSGS, minimal-change nephrotic syndrome, and GN. In addition, in urinary podocytes from patients with FSGS and minimal-change nephrotic syndrome, we analyzed podocyte hypertrophy and mitotic catastrophe using immunostaining of p21 and phospho-ribosomal protein S6. The size of the urinary podocytes was strikingly larger in samples obtained from patients with FSGS compared with those with minimal-change nephrotic syndrome and GN (P=0.008). Urinary podocytes from patients with FSGS had a higher frequency of positive immunostaining for p21 (P<0.001) and phospho-ribosomal protein S6 (P=0.02) than those from patients with minimal-change nephrotic syndrome. Characteristic features of mitotic catastrophe were more commonly observed in FSGS than in minimal-change nephrotic syndrome urinary samples (P=0.001). We posit that the significant increase in the size of urinary podocytes in FSGS, compared with those in minimal-change nephrotic syndrome, may be explained by hypertrophy and mitotic catastrophe.


Exploring the Coordination of Cardiac Ion Channels With Action Potential Clamp Technique.
The patch clamp technique underwent continual advancement and developed numerous variants in cardiac electrophysiology since its introduction in the late 1970s. In the beginning, the capability of the technique was limited to recording one single current from one cell stimulated with a rectangular command pulse. Since that time, the technique has been extended to record multiple currents under various command pulses including action potential. The current review summarizes the development of the patch clamp technique in cardiac electrophysiology with special focus on the potential applications in integrative physiology.


Neighborhood social capital, parenting strain, and personal mastery among female primary caregivers of children.
Neighborhood social capital-resources inherent within community networks-has been identified as a potential facilitator of personal well-being. We test hypotheses concerning how neighborhood social capital moderates the influence of parenting strain on mastery (individuals' understanding of their ability to control personal life circumstances) for female primary caregivers of children. First, we test how different forms of neighborhood social capital-social support, social leverage (information exchange), informal social control, and neighborhood organization participation-modify the association between parenting strain and mastery. Second, we test whether such moderation depends on one's access to these forms via neighbor ties. Analyses of Los Angeles Family and Neighborhood Survey data (N = 765) indicate that the negative relationship between parenting strain and mastery worsens as informal social control increases. Social support and informal social control, however, buffer this parenting strain-mastery relationship when caregivers have stronger ties to neighbors. Our findings implicate mechanisms of "negative social capital" and warrant more nuanced considerations of neighborhood social capital's health-promoting potential.


Effects of subcutaneous and intracerebroventricular administration of the sigma receptor ligand 1,3-Di-o-tolylguanidine on body temperature in the rat: interactions with BMY 14802 and rimcazole.
The current study investigated the effects of the acute s.c. and i.c.v. administration of 1,3-di-o-tolylguanidine (DTG) on body temperature in rats. The effects of putative sigma receptor antagonists BMY 14802 and rimcazole on DTG-induced changes in body temperature also were evaluated. The acute s.c. administration of DTG (10.0 and 20.0 mg/kg) produced hypothermia but no observable behavioral effects. Similarly, the acute i.c.v. administration of DTG (12.0-100.0 micrograms/rat) produced hypothermia, but ataxia occurred after this route of administration. The s.c. administration of BMY 14802 alone (25.0 mg/kg) decreased body temperature and enhanced the DTG-induced hypothermia, whereas the administration of rimcazole (25.0 mg/kg) neither altered body temperature nor affected the hypothermia produced by DTG. Neither BMY 14802 nor rimcazole produced any behavioral effects when administered alone. The inability of the putative sigma receptor antagonists BMY 14802 and rimcazole to antagonize DTG-induced hypothermia suggests that either these compounds at the dose used have little sigma receptor antagonist activity, or that the DTG-induced hypothermia is not due to specific interactions with sigma receptors.


[The transition of psychotropic drugs in Japanese Pharmacopoeia (JP) (Part 6): the knowledge and judgment about the sort as the medicine on valerianae radix].
It was thought that valerianae had circulated as the public drugs in Japan since the middle of Edo period and also thought the European valerianae was introduced for the first time in the late Edo period. Then, Japanese valerianae was widely used as the same effective drug as European valerianae in the Meiji period. By the beginning of the First World War, Japanese government encouraged the use of domestic drugs in Japan. As a result, Japanese valerianae was widely grown all over Japan and became the majority of the circulation on the market. Japanese valerianae contained more volatile oil than European valerianae. Therefore, Japanese valelrianae was exported mainly to Germany until the Second World War and was highly evaluated from all over the world. After the Second World War, Japanese valerianae lost its economical advantage and the production of Japanese valerianae declined. Now, Japanese valerianae was barely grown only in Hokkaido. The pharmaceutical action of Japanese valerianae is generous. So, it is thought that valerianae radix may be used for raw materials of general drugs in the future, too.


Ultrafast carrier dynamics in 2D-2D hybrid structures of functionalized GO and CdSe nanoplatelets.
Considerable attention has been paid to designing graphene based 2D hybrid nanostructures for their potential applications in various areas from healthcare to energy harvesting. Herein, we have prepared 2D-2D hybrid structures of 2D CdSe nanoplatelets (NPLs) with thiol (-SH) functionalized reduced graphene oxide (G-Ph-SH). Microscopic and spectroscopic studies reveal that the G-Ph-SH surface is successfully decorated by CdSe NPLs through a thiophenol (-SH) linker. The significant photoluminescence quenching (65%) and the shortening of decay time from 1 ns to 0.4 ns of CdSe NPLs are observed after adding 100 μg of G-Ph-SH. Furthermore, the femto-second transient absorption spectroscopic (fs-TAS) study reveals that the growth time of CdSe NPLs in the composite is reduced to 0.4 ps from 0.8 ps due to faster hot electron cooling. A faster component of 1.4 ps in the kinetic parameters of the composite system further suggests that the ultrafast electron transfer occurs from the conduction band of CdSe NPLs to surface functionalized reduced graphene oxide. This type of 2D-2D hybrid structure may open up new possibilities in light harvesting applications.


Self-assessment of empathy uncovers defective self-awareness in mild cognitive impairment.
Self-assessment scales are broadly used to evaluate empathy in neurological patients, but it is conceivable that some discrepancy with caregiver evaluation may emerge as consequence of reduced self-awareness. The aim of the present study was to verify the presence of discrepancies in the self-assessment of empathy in subjects with mild cognitive impairment (MCI) and to explore their neural correlates. Twenty MCI patients and 38 healthy controls (HCs) underwent the Interpersonal Reactivity Index (IRI), exploring the following four aspects of empathy: perspective taking (PT), fantasy, empathic concern, and personal distress. The questionnaire was administered in two modalities: self-administered, and administered to an informant, and the scores were compared. The correlation between discrepancies and regional cortical thickness was assessed. The self-administered version of IRI showed higher PT scores in MCI as compared to HC (p = .017), with no differences detected in the other subscales. The difference between the scores obtained in the self-administered and in the informant-administered IRI-PT was significantly higher in MCI than in HCs (p = .006). The self-assessment of empathy in subjects with MCI may be misleading because of a tendency toward an overestimation of the PT ability, typically considered as a cognitive component of empathy. Our results may reflect a particular aspect of reduced self-awareness in MCI subjects. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Structural determination of wild-type lactose permease.
Here we describe an x-ray structure of wild-type lactose permease (LacY) from Escherichia coli determined by manipulating phospholipid content during crystallization. The structure exhibits the same global fold as the previous x-ray structures of a mutant that binds sugar but cannot catalyze translocation across the membrane. LacY is organized into two six-helix bundles with twofold pseudosymmetry separated by a large interior hydrophilic cavity open only to the cytoplasmic side and containing the side chains important for sugar and H(+) binding. To initiate transport, binding of sugar and/or an H(+) electrochemical gradient increases the probability of opening on the periplasmic side. Because the inward-facing conformation represents the lowest free-energy state, the rate-limiting step for transport may be the conformational change leading to the outward-facing conformation.


Fluorofenidone affects hepatic stellate cell activation in hepatic fibrosis by targeting the TGF-β1/Smad and MAPK signaling pathways.
The aim of the present research was to study the therapeutic impacts of fluorofenidone (AKF-PD) on pig serum (PS)-induced liver fibrosis in rats and the complex molecular mechanisms of its effects on hepatic stellate cells (HSCs). Wistar rats were randomly divided into normal control, PS and PS/AKF-PD treatment groups. The activated human HSC LX-2 cell line was also treated with AKF-PD. The expression of collagen I and III, and α-smooth muscle actin (α-SMA) was determined by immunohistochemical staining and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting and/or RT-qPCR analyses were used to determine the expression of transforming growth factor (TGF)-β1, α-SMA, collagen I, mothers against decapentaplegic homolog (Smad)-3, extracellular signal-regulated kinase (ERK)1/2, p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). AKF-PD attenuated the degree of hepatic fibrosis and liver injury in vivo, which was associated with the downregulation of collagen I and III, and α-SMA at the mRNA and protein levels. In vitro, AKF-PD treatment significantly reduced the TGF-β1-induced activation of HSCs, as determined by the reduction in collagen I and α-SMA protein expression. The TGF-β1-induced upregulation of the phosphorylation of Smad 3, ERK1/2, p38 and JNK was attenuated by AKF-PD treatment. These findings suggested that AKF-PD attenuated the progression of hepatic fibrosis by suppressing HSCs activation via the TGF-β1/Smad and MAPK signaling pathways, and therefore that AKF-PD may be suitable for use as a novel therapeutic agent against liver fibrosis.


The role of the fibroblast growth factor family in bone-related diseases.
Fibroblast growth factor (FGF) family members are important regulators of cell growth, proliferation, differentiation, and regeneration. The abnormal expression of certain FGF family members can cause skeletal diseases, including achondroplasia, craniosynostosis syndrome, osteoarthritis, and Kashin-Beck disease. Accumulating evidence shows that FGFs play a crucial role in the growth and proliferation of bone and in the pathogenesis of certain bone-related diseases. Here, we review the involvement of FGFs in bone-related processes and diseases; FGF1 in the differentiation of human bone marrow mesenchymal stem cells and fracture repair; FGF2, FGF9, and FGF18 in osteoarthritis; FGF6 in bone and muscle injury; FGF8 in osteoarthritis and Kashin-Beck disease; and FGF21 and FGF23 on bone regulation. These findings indicate that FGFs are targets for novel therapeutic interventions for bone-related diseases.


Role of exercise in estrogen deficiency-induced sarcopenia.
A decline in estrogen levels during menopause is associated with the loss of muscle mass and function, and it can accelerate sarcopenia. However, with the growing number of postmenopausal women due to the increase in life expectancy, the effects of estrogen on skeletal muscle are not completely understood. This article reviews the relationship between estrogen deficiency and skeletal muscle, its potential mechanisms, including those involving mitochondria, and the effects of exercise on estrogen deficiency-induced skeletal muscle impairment. In particular, mitochondrial dysfunction induced by estrogen deficiency accelerates sarcopenia via mitochondrial dynamics, mitophagy, and mitochondrial-mediated apoptosis. It is well known that exercise training is essential for health, including for the improvement of sarcopenia. This review highlights the importance of exercise training (aerobic and resistance exercise) as a therapeutic intervention against estrogen deficiency-induced sarcopenia.


Treatment of Vitamin K Deficiency in Hemodialysis Patients - A Pilot Study Comparing Menaquinone-7 Tablets and a Vitamin K Rich Diet.
Vitamin K deficiency and hence a high level of plasma dephosphorylated undercarboxylated matrix Gla protein (dp-ucMGP) is frequent in patients on hemodialysis. This group is recommended to restrict their potassium intake which often leads to restriction of vitamin K rich foods. A menaquinone-7 (MK-7) supplement has been shown to decrease dp-ucMGP, but it has yet to be examined if a vitamin K rich diet could be equally effective. A prospective randomized crossover intervention trial with two arms; 6 weeks of 360 μg MK-7 tablet/day and 6 weeks of a vitamin K rich diet with a 3-week washout period in between. Participants were 10 patients in hemodialysis and the primary outcome measures were changes in dp-ucMGP, total MGP (tMGP), and undercarboxylated osteocalcin (ucOC). Furthermore, the level of potassium and phylloquinone in broccoli was determined after different durations of boiling. During the MK-7 intervention the dp-ucMGP and ucOC decreased significantly compared to baseline (-0.42 [-0.93; -0.22] nmol/L (p=<0.01) and -1.85 [-2.91; -1.30] nmol/L (p<0.01)), while these were unchanged during the dietary intervention (0.03 [-0.64; 0.37] nmol/L (p=1.00) and 0.30 [-1.71; 1.41] nmol/L (p=0.77)). Between the two interventions there was a greater decrease in ucOC (p=0.02) during the MK-7 compared to the dietary period. No significant changes in the total MGP levels were found in any of the periods. The retention of potassium following boiling for 2 minutes and 8 minutes was 76% and 49%, respectively, while for phylloquinone the retention was 92%, and independent of duration of boiling. A daily MK-7 supplement for 6 weeks lowered dp-ucMGP and ucOC significantly, while a vitamin K rich diet was not able to induce any significant effect. Boiled broccoli maintains a reasonable content of phylloquinone while potassium is extracted and is a reasonable source of phylloquinone for patients on hemodialysis.


Retaliation as a response to procedural unfairness: a self-regulatory approach.
When does procedural unfairness result in retaliation, and why do recipients of unfair treatment sometimes pursue and other times inhibit retaliation? Five studies addressed these questions. The authors proposed and found that regulatory focus moderates retaliation against an unfairness-enacting authority: Promotion-focus participants were more likely to retaliate than prevention-focus participants. Promotion focus was associated with, and also heightened the accessibility of, the individual self. In turn, individual-self accessibility influenced retaliation. In fact, prevention-focus participants were as retaliatory as promotion-focus participants under conditions of high individual-self accessibility. Implications for the procedural fairness and regulatory focus literatures are discussed, and suggestions for future research are offered.


Autophagosome formation: core machinery and adaptations.
Eukaryotic cells employ autophagy to degrade damaged or obsolete organelles and proteins. Central to this process is the formation of autophagosomes, double-membrane vesicles responsible for delivering cytoplasmic material to lysosomes. In the past decade many autophagy-related genes, ATG, have been identified that are required for selective and/or nonselective autophagic functions. In all types of autophagy, a core molecular machinery has a critical role in forming sequestering vesicles, the autophagosome, which is the hallmark morphological feature of this dynamic process. Additional components allow autophagy to adapt to the changing needs of the cell.


Long-term dietary intake and nutritional deficiencies following sleeve gastrectomy or Roux-En-Y gastric bypass in a mediterranean population.
Data on long-term dietary changes and nutritional deficiencies after sleeve gastrectomy (SG) in grade 3 obese patients are scarce. To prospectively compare dietary changes and nutritional deficiencies in grade 3 obese patients 5 years after SG and Roux-en-y gastric bypass (GBP). Three hundred and fifty-five patients who had SG (n=61) or GBP (n=294) (May 2001-December 2006) at a Spanish university hospital. Longitudinal, prospective, observational study. PRIMARY OUTCOMES/STATISTICAL ANALYSES: Changes in energy, macronutrient, and micronutrient intake, and weight loss were analyzed using mixed models for repeated measurements. At the 5-year follow-up visit, the percentage of excess weight loss (P=0.420) and daily energy intake (P=0.826), as well as the proportion of energy from carbohydrates (P=0.303), protein (P=0.600), and fat (P=0.541) did not differ between surgical groups. Energy intake (P=0.004), baseline weight (P<0.001), and time period (P<0.001), but not the proportion of different macronutrients or the type of surgery, independently predicted the percentage excess weight loss over time. After SG or GBP, the mean daily dietary intake of calcium, magnesium, phosphorus, and iron was less than the current recommendations. Despite universal supplementation, the prevalence of nutritional deficiencies was comparable after SG or GBP, with 25-hydroxyvitamin D being the most commonly observed deficiency (SG, 93.3% to 100%; GBP, 90.9% to 85.7%, P=not significant). In an adjusted multivariate regression model, energy intake and lipid intake independently predicted plasma 25(OH)-vitamin D levels. Data show that SG and GBP are associated with similar long-term weight loss with no differences in terms of dietary intake. Furthermore, data demonstrate that both types of surgeries carry comparable nutritional consequences.


Increased estrogen-16 alpha-hydroxylase activity in women with breast and endometrial cancer.
We have measured the three principal oxidative transformations of estradiol by means of a radiometric procedure in women with breast or endometrial cancer and in age matched controls. No difference between the 17 beta-ol oxidation or 2-hydroxylation of the hormone was observed between the study groups. In contrast, 16 alpha-hydroxylation was strikingly elevated in the women with breast and endometrial cancer relative to the age matched controls. Evidence is presented that this increased activity precedes the clinical evidence of the disease and that it represents a significant risk factor for these estrogen dependent tumors. This risk may be mediated by one of the products of 16 alpha-hydroxylation, 16 alpha-hydroxyestrone, which exhibits unique biological properties.


Data processing for intensity based fiber optic sensors.
The design of a data processing prototype for intensity based fiber optic sensors is presented. This processing unit fulfills the requirement of a simple and reliable measurement technique to the laboratory user. In this particular experiment, the data processing unit was tested for an optical fiber displacement sensor.


Indoleamine 2, 3-Dioxygenase 1 Mediates Survival Signals in Chronic Lymphocytic Leukemia via Kynurenine/Aryl Hydrocarbon Receptor-Mediated MCL1 Modulation.
The indoleamine 2,3-dioxygenase 1 (IDO1) metabolic circuitry, comprising the first tryptophan (Trp) catabolite L-kynurenine (Kyn) and the aryl hydrocarbon receptor (AHR), has emerged as a mechanism of cancer immune evasion. Here, we investigated the functional role of the IDO1/Kyn/AHR axis in chronic lymphocytic leukemia (CLL). Our data show that CLL cells expressed an active form of the IDO1 enzyme and microenvironmental stimuli can positively modulate its expression. Interferon (IFN)-γ induces IDO1 expression through the Jak/STAT1 pathway and mediates Kyn production concomitantly with Trp consumption in CLL-conditioned media, while INCB018424 (ruxolitinib), a JAK1/2 inhibitor, impaired both effects. To characterize the involvement of IDO1 in leukemic cell maintenance, we overexpressed IDO1 by vector transfection measuring enhanced resistance to spontaneous apoptosis. IDO1 pro-survival influence was confirmed by treating CLL cells with Kyn, which mediated the increase of induced myeloid leukemia cell differentiation protein (MCL1). Conversely, AHR silencing or its blockade via CH-223191 improved the apoptosis of leukemic clones and mitigated MCL1 expression. Moreover, Kyn-treated CLL cells are less affected by the pro-apoptotic effect of ABT-199 (venetoclax), while CH-223191 showed synergistic/additive cytotoxicity with this drug. Lastly, targeting directly MCL1 in CLL cells with AMG-176, we abrogate the pro-survival effect of Kyn. In conclusion, our data identify IDO1/Kyn/AHR signaling as a new therapeutic target for CLL, describing for the first time its role in CLL pathobiology.


Metals, Nanoparticles, Particulate Matter, and Cognitive Decline.
Exposure to metals is ubiquitous and emission sources include gasoline, diesel, smoke from wildfires, contaminated soil, water and food, medical implants, waste recycling facilities, subway exposures, and occupational environments. PM2.5 exposure is associated with impaired cognitive performance, neurobehavioral alterations, incidence of dementia, and Alzheimer's disease (AD) risk. Heavy-duty diesel vehicles are major emitters of metal-rich PM2.5 and nanoparticles in Metropolitan Mexico City (MMC). Cognitive impairment was investigated in 336 clinically healthy, middle-class, Mexican volunteers, age 29.2 ± 13.3 years with 13.7 ± 2.4 years of education using the Montreal Cognitive Assessment (MoCA). MoCA scores varied with age and residency in three Mexican cities with cognition deficits impacting ~74% of the young middle-class population (MoCA ≤ 25). MMC residents ≥31 years ( x ¯ 46.2 ± 11.8 y) had MoCA x ¯ 20.4 ± 3.4 vs. low pollution controls 25.2 ± 2.4 (p < 0.0001). Formal education years positively impacted MoCA total scores across all participants (p < 0.0001). Residency in PM2.5 polluted cities impacts multi-domain cognitive performance. Identifying and making every effort to lower key pollutants impacting neural risk trajectories and monitoring cognitive longitudinal performance are urgent. PM2.5 emission control should be prioritized, metal emissions targeted, and neuroprevention interventions implemented early.


Association between thiazolidinedione treatment and risk of macular edema among patients with type 2 diabetes.
Findings of prior studies have been inconclusive about the ocular effects of thiazolidinediones on diabetic macular edema (DME). We evaluated, in patients with type 2 diabetes (T2D), the short-term and long-term risks of developing DME among users vs nonusers of thiazolidinediones. A retrospective cohort study of 103,368 patients with T2D and no DME at baseline using The Health Improvement Network (THIN) database. Clinical, biochemical, and demographic information was obtained for the period January 1, 2000, through November 30, 2009. At 1 year, the incidence of DME was 1.3% (n = 41) and 0.2% (n = 227) among thiazolidinedione users (n = 3227) and nonusers (n = 100,141), respectively (odds ratio [OR], 5.7 [95% CI, 4.1-7.9]). After Cox multiple regression analysis (adjusted for age; systolic blood pressure; levels of lipids and hemoglobin A(1c); and use of aspirin, fibrates, insulin, oral antidiabetic drugs, or renin-angiotensin system blockers), multiple imputation analysis to adjust for missing values, and propensity score analysis to exclude for any selection bias, thiazolidinedione use was associated with an increased risk of DME at 1-year follow-up (OR, 2.3 [95% CI, 1.5-3.6]) and 10-year follow-up (hazard ratio [HR], 2.3; [95% CI, 1.7-3.0]). The effect was similar for pioglitazone and rosiglitazone. Combination therapy with insulin plus a thiazolidinedione was associated with a higher risk of DME after propensity score adjustment (HR, 3.0 [95% CI, 1.5-5.9]), while aspirin use (HR, 0.6 [95% CI, 0.4-0.9]) and angiotensin-converting enzyme inhibitor use (HR, 0.4 [95% CI, 0.2-0.7]) were associated with a reduced risk of DME. Among patients with T2D, treatment with a thiazolidinedione was associated with an increased risk of DME at 1-year and 10-year follow-up evaluations.


How do parents find out about the ketogenic diet?
It has been previously reported that child neurologists often view the ketogenic diet (KD) as a treatment of last resort. An anonymous survey was provided to parents of 107 consecutive children starting the KD at our institution. The average time from epilepsy to KD onset was 2.8years, but the average wait time for KD onset was only 1.7months after referral. The most common reason for starting the KD was seizure reduction, followed by less intense seizures, medication reduction, and cognitive improvement. The majority (72%) obtained information about the KD from their neurologist; however, more than half also had viewed related websites. The mean neurologist supportiveness score was 7.9/10; 53% reporting their neurologist as maximally supportive (score of 10). A score of 10 was more likely seen in those who also scored their pediatrician with 10 (69% vs. 15%, p<0.001) and who were self-referred from our institution (56% vs. 27%, p=0.001).


Selective synthesis of manganese oxide nanostructures for electrocatalytic oxygen reduction.
This work presents two points with respect to manganese oxide (MnO(x)) nanomaterials: their controllable synthesis with desired phases and shapes together with their applications as catalysts for oxygen reduction and Al/air batteries. Solid MnO(x) with crystalline phases of MnOOH, Mn(2)O(3), and MnO(2) as well as shapes of the sphere, wire, rod, and particle were prepared through a simple one-pot hydrothermal route. Selective preparation was achieved by adjusting the surfactant concentration that controls simultaneously the growth thermodynamic and dynamic parameters of MnO(x) nanocrystals. Electrochemical investigations show that the obtained Mn(2)O(3) nanowires, which possess a large aspect ratio and preferentially exposed (222) crystal surfaces, exhibit remarkable catalytic activity (comparable to Pt/C counterparts) toward the electroreduction of oxygen in alkaline media. The tailored MnO(x) nanostructures may find prospective applications as low-cost catalysts for alkaline fuel cells and metal/air batteries.


Strategies to Optimize Dual Antiplatelet Therapy After Coronary Artery Stenting in Acute Coronary Syndrome.
The use of aspirin and a P2Y12 receptor antagonist as dual antiplatelet therapy (DAPT) has become the treatment of choice in patients with acute coronary syndrome (ACS) and percutaneous coronary intervention to prevent recurrent thrombotic events. Although DAPT is beneficial for most patients, few patients still experience recurrent thrombotic events and increased bleeding episodes. This article reviews current literature to identify various approaches that may enhance the DAPT benefit-risk ratio in patients with ACS. Three strategies addressed in this article include the following-(1) use of more potent antiplatelet agents other than clopidogrel; (2) addition of direct oral anticoagulants (DOACs) to DAPT; and (3) optimizing DAPT duration. Although the use of prasugrel or ticagrelor improves treatment efficacy, their use has been associated with increased risk of bleeding compared to clopidogrel. The combination of DOACs and DAPT may not be the most viable strategy because of its limited cardiovascular benefits and increased bleeding risks. The optimal duration of DAPT duration remains controversial. Most guidelines recommend 6 to 12 months of DAPT, whereas emerging studies have shown benefit for both shorter and longer duration of treatment. Risk stratification tools such as the DAPT score may play a role in individualizing DAPT duration according to patient's ischemic and bleeding risks.


Spanish multicentre trial of recombinant somatropin. Spanish Collaborative Group.
A total of 42 patients (22 previously untreated and 20 previously treated) with GH deficiency were included in a Spanish multicentre trial of recombinant somatropin, 0.5 IU/kg/week. In previously untreated patients typical catch-up growth was observed and the height velocity increased from 3.3 +/- 0.6 cm/year to 9.8 +/- 2.4 cm/year during 1 year of therapy. In previously treated children, the height velocity was maintained (7.2 +/- 2.0 cm/year at the start and 7.9 +/- 1.6 cm/year after 1 year). No anti-GH antibodies were detected in previously untreated patients, and they disappeared from previously treated ones. No adverse reactions were reported.


Enantioselective isothiourea-catalysed reversible Michael addition of aryl esters to 2-benzylidene malononitriles.
Catalytic enantioselective transformations usually rely upon optimal enantioselectivity being observed in kinetically controlled reaction processes, with energy differences between diastereoisomeric transition state energies translating to stereoisomeric product ratios. Herein, stereoselectivity resulting from an unusual reversible Michael addition of an aryl ester to 2-benzylidene malononitrile electrophiles using an isothiourea as a Lewis base catalyst is demonstrated. Notably, the basicity of the aryloxide component and reactivity of the isothiourea Lewis base both affect the observed product selectivity, with control studies and crossover experiments indicating the feasibility of a constructive reversible Michael addition from the desired product. When this reversible addition is coupled with a crystallisation-induced diastereomer transformation (CIDT) it allows isolation of products in high yield and stereocontrol (14 examples, up to 95 : 5 dr and 99 : 1 er). Application of this process to gram scale, plus derivatisations to provide further useful products, is demonstrated.


Bilateral Optic Disc Swelling with Preserved Visual Function Associated with Giant Cell Arteritis.
A 68-year-old Japanese man was introduced to our hospital for optic disc swelling (ODS) in his both eyes (OU). Other than floaters in his right eye, he did not report any symptoms including blurred vision, visual field defect, and ocular pain. Light reflex was prompt and complete OU, and critical flicker frequency was within the normal range OU. By fluorescein angiography, hyperfluorescence was detected on optic discs OU; however, no fluorescein leakage or filling defect was observed. By Goldmann perimetry, enlargement of the Mariotte blind spot was revealed OU, while no central scotoma or remarkable visual field defects were detected. By neuroimaging and lumbar puncture, papilledema due to intracranial pressure elevation was denied. Based on the reassessment of fundus findings, narrowing and segmental whitening/sheathing of peripapillary vessels predominantly to arterioles were realized, and systemic arteritis was suspected. Based on the subject age, elevation of erythrocyte sedimentation rate, positron emission tomography findings in the aorta, and MRI findings in temporal arteries, underlying giant cell arteritis (GCA) was diagnosed. After the start of systemic and local steroid therapies, ODS improved OU. Although rare, bilateral ODS with no visual disturbance can occur in patients with GCA. This case emphasizes the importance of careful assessment of ocular findings to reach the correct diagnosis of even a rare cause of ODS.


[Successful Management of Cardiopulmonary Bypass Using Heparin in a Patient with Previous History of Heparin-induced Thrombocytopenia].
Anti-coagulant management of cardiopulmonary bypass for the patient complicated with heparin-induced thrombocytopenia (HIT) is difficult. A woman of late 50's with a previous history of HIT was scheduled for mitral valve replacement, tricuspid valvuloplasty and coronary artery bypass graft. We knew that heparin antibody was negative by serologic and functional assay before the operation. According to the HIT guideline, we planned to use heparin only during cardiopulmonary bypass and to use argatroban for other catheters. Although the platelet count continued decreasing up to the 5th postoperative day unless the transfusion of platelets, heparin antibody was negative on the first postoperative day. But, it was thought that HIT would develop from 5 days to 10 days after using heparin. Therefore, we had to examine heparin antibody on the 5th postoperative day at least for the patients with a history of HIT. In the future, it is important to observe the patient carefully and examine heparin antibody.


Clinical scenario 1 is associated with winter onset of acute heart failure.
Several reports have evaluated the association between seasonal variation and acute heart failure (AHF) onset. Cold weather may induce AHF, but the clinical characteristics of patients susceptible to AHF during winter have not been established. Clinical Scenario (CS) is used in the early clinical management of AHF, so we investigated the relationship between CS classification and winter onset of AHF in Japan. We enrolled 582 patients hospitalized for AHF and compared the frequency of AHF among the 4 seasons in each CS group to clarify the clinical characteristics of the winter onset group. Significant increase of AHF during winter was seen in CS1 (systolic blood pressure [SBP] (>140 mmHg) (P=0.01) but not in CS2 (SBP ≥ 100 and ≤ 140 mmHg) or CS3 (SBP <100 mmHg). CS1 patients were divided into winter and other season admission groups. In multivariate analysis, only lack of loop diuretic use was associated with winter admission of CS1 patients (odds ratio 0.562, 95% confidence interval: 0.256-0.798, P=0.006). Winter predominance of AHF was seen only in CS1, and lack of loop diuretic use was a risk factor for winter onset. Future studies are necessary to confirm whether loop diuretics are useful in preventing AHF with CS1 in winter.


Our current understanding of the toxicity of altered mito-ribosomal fidelity during mitochondrial protein synthesis: What can it tell us about human disease?
Altered mito-ribosomal fidelity is an important and insufficiently understood causative agent of mitochondrial dysfunction. Its pathogenic effects are particularly well-known in the case of mitochondrially induced deafness, due to the existence of the, so called, ototoxic variants at positions 847C (m.1494C) and 908A (m.1555A) of 12S mitochondrial (mt-) rRNA. It was shown long ago that the deleterious effects of these variants could remain dormant until an external stimulus triggered their pathogenicity. Yet, the link from the fidelity defect at the mito-ribosomal level to its phenotypic manifestation remained obscure. Recent work with fidelity-impaired mito-ribosomes, carrying error-prone and hyper-accurate mutations in mito-ribosomal proteins, have started to reveal the complexities of the phenotypic manifestation of mito-ribosomal fidelity defects, leading to a new understanding of mtDNA disease. While much needs to be done to arrive to a clear picture of how defects at the level of mito-ribosomal translation eventually result in the complex patterns of disease observed in patients, the current evidence indicates that altered mito-ribosome function, even at very low levels, may become highly pathogenic. The aims of this review are three-fold. First, we compare the molecular details associated with mito-ribosomal fidelity to those of general ribosomal fidelity. Second, we gather information on the cellular and organismal phenotypes associated with defective translational fidelity in order to provide the necessary grounds for an understanding of the phenotypic manifestation of defective mito-ribosomal fidelity. Finally, the results of recent experiments directly tackling mito-ribosomal fidelity are reviewed and future paths of investigation are discussed.


N omega-hydroxyl-L-arginine, an intermediate in the L-arginine to nitric oxide pathway, is a strong inhibitor of liver and macrophage arginase.
N omega-Hydroxy-L-arginine (L-NOHA) is a potent inhibitor of the hydrolysis of L-arginine (L-Arg) to L-ornithine (L-Orn) catalyzed by purified bovine liver arginase (BLA). It appears as one of the most powerful arginase inhibitors reported so far (Ki = 150 microM). The other products of NO synthase are either without effect (NO2-, NO3-) or much weaker inhibitors (L-citrulline (L-Cit) and NO) of BLA. Products derived from a possible hydrolysis of L-Arg (L-Orn and urea) or of L-NOHA (L-Cit, hydroxyurea and hydroxylamine) are also inactive toward BLA at concentrations up to 2 mM. The configuration of L-NOHA is important as D-NOHA is much less active, and its free -COOH and alpha-NH2 functions are required for recognition of BLA. L-NOHA is also a potent inhibitor of the arginase activity of rat liver homogenates and of murine macrophages (IC50 of 150 and 450 microM, respectively). These remarkable properties of L-NOHA could play a role in the modulation of the biosynthesis of the biological mediator NO by increasing local L-Arg concentrations.


Primary cCT Imaging Based Clinico-Neurological Assessment-Calling for Addition of Telestroke Video Consultation in Patients With Intracerebral Hemorrhage.
Background and Purpose: Intracerebral hemorrhage (ICH) requires rapid decision making to decrease morbidity and mortality although time frame and optimal therapy are still ill defined. Ideally, specialized neurologists, neurosurgeons, and (neuro-) radiologists who know the patient's clinical status and their cerebral computed tomography imaging (cCT) make a joint decision on the clinical management. However, in telestroke networks, a shift toward cCT imaging criteria used for decision making can be observed for practical reasons. Here we investigated the "reverse correlation" from cCT imaging to the actual clinical presentation as evaluated by the Glasgow Coma Scale (GCS) and the National Institutes of Health Stroke Scale (NIHSS). Methods: CCT images and basic information (age, sex, and time of onset) of 50 patients with hypertensive and lobar ICH were presented to 14 experienced neurologists and 15 neurosurgeons. Based on this information, the NIHSS and GCS scores were estimated for each patient. The differences between the actual GCS and NIHSS scores and the cCT-imaging-based estimated scores were plotted in a bland-Altman plot. Results: The average estimated GCS score mainly based on cCT imaging was 12. 4 ± 2.8 (actual value: 13.0 ± 2.5; p = 0.100), the estimated NIHSS score was 13.9 ± 9.1 (actual value: 10.8 ± 7.3; p < 0.001). Thus, in cCT-imaging-based evaluation, the neurological status of patients especially employing the NIHSS was estimated poorer, particularly in patients with lobar ICH. "Reverse clinical" evaluation based on cCT-imaging alone may increase the rate of intubation and secondary transferal and neurosurgical treatment. Telestroke networks should consider both, videoassessment of the actual clinical picture and cCT-imaging findings to make appropriate acute treatment decisions.


Cloning and characterization of hELD/OSA1, a novel BRG1 interacting protein.
A highly conserved multisubunit enzymic complex, SWI/SNF, participates in the regulation of eukaryote gene expression through its ability to remodel chromatin. While a single component of SWI/SNF, Swi2 or a related protein, can perform this function in vitro, the other components appear to modulate the activity and specificity of the complex in vivo. Here we describe the cloning of hELD/OSA1, a 189 KDa human homologue of Drosophila Eld/Osa protein, a constituent of Drosophila SWI/SNF. By comparing conserved peptide sequences in Eld/Osa homologues we define three domains common to all family members. A putative DNA binding domain, or ARID (AT-rich DNA-interacting domain), may function in targetting SWI/SNF to chromatin. Two other domains unique to Eld/Osa proteins, EHD1 and EHD2, map to the C-terminus. We show that EHD2 mediates binding to Brahma-related gene 1 (BRG1), a human homologue of yeast Swi2. EHD1 and EHD2 also appear capable of interacting with each other. Using an antibody raised against EHD2 of hELD/OSA1, we detected Eld/Osa1 in endogenous SWI/SNF complexes derived from mouse brain.


Bone histology in adults with aseptic necrosis. Histomorphometric evaluation of iliac biopsies in seventy-seven patients.
We studied the bone histology by histomorphometric methods in transiliac bone-biopsy specimens from seventy-seven adult patients with aseptic osteonecrosis and normal kidney function. The trabecular bone volume, trabecular osteoid volume, trabecular osteoid surfaces, thickness index of osteoid seams, total resorption surfaces, calcification rate, tetracycline-labeled surfaces, and bone-formation rate at the basic multicellular unit level and at the tissue level were determined. Histological evidence of osteomalacia was found in nine patients, of whom four were alcoholics. In the remaining sixty-eight patients--fifteen treated with corticosteroids, twenty-nine alcoholics, and twenty-four who did not have any detectable etiological factor--a common histomorphometric profile was found. This consisted morphologically of a reduction in trabecular bone volume and in the thickness of osteoid seams, and dynamically of a reduction in calcification rate and in total labeled surfaces. All of these changes suggested a marked decrease in osteoblastic appositional rate and in bone-formation rate at the cell and tissue levels. This could induce a healing defect of microfractures and thus facilitate subchondral fractures. This histological study indicated that non-apparent bone disease--either osteoporosis or osteomalacia--may underlie aseptic osteonecrosis in almost all patients, and be found even when blood and urinary biochemical parameters, usually reflecting bone-remodeling, are normal. An iliac-crest bone biopsy with static and dynamic histomorphometric study is the appropriate method for detecting these abnormalities. These results are of importance for understanding the pathophysiological mechanisms underlying osteonecrosis as well as its prevention and treatment.


Japanese experience of evolving nurses' roles in changing social contexts.
To discuss the evolving roles of Japanese nurses in meeting the goals and concerns of ongoing global sustainable development. Japanese nurses' roles have evolved as the needs of the country and the communities they served, changed over time. The comprehensive public healthcare services in Japan were provided by the cooperation of hospitals and public health nurses. The nursing profession is exploring ways to identify and systemize nursing skills and competencies that address global health initiatives for sustainable development goals. This paper is based on the summary of a symposium, (part of the 2015 annual meeting of the Japan Association for International Health) with panel members including experts from Japan's Official Development Assistance. The evolving role of nurses in response to national and international needs is illustrated by nursing practices from Japan. Japanese public health nurses have also assisted overseas healthcare plans. In recent catastrophes, Japanese nurses assumed the roles of community health coordinators for restoration and maintenance of public health. The Japanese experience shows that nursing professionals are best placed to work with community health issues, high-risk situations and vulnerable communities. Their cooperation can address current social needs and help global communities to transform our world. Nurses have tremendous potential to make transformative changes in health and bring about the necessary paradigm shift. They must be involved in global sustainable development goals, health policies and disaster risk management. A mutual understanding of global citizen and nurses will help to renew and strengthen their capacities. Nursing professionals can contribute effectively to achieve national and global health goals and make transformative changes.


Systems metabolic engineering as an enabling technology in accomplishing sustainable development goals.
With pressing issues arising in recent years, the United Nations proposed 17 Sustainable Development Goals (SDGs) as an agenda urging international cooperations for sustainable development. In this perspective, we examine the roles of systems metabolic engineering (SysME) and its contribution to improving the quality of life and protecting our environment, presenting how this field of study offers resolutions to the SDGs with relevant examples. We conclude with offering our opinion on the current state of SysME and the direction it should move forward in the generations to come, explicitly focusing on addressing the SDGs.


Atomically Dispersed Cobalt Sites on Graphene as Efficient Periodate Activators for Selective Organic Pollutant Degradation.
Pollutant degradation via periodate (IO4-)-based advanced oxidation processes (AOPs) provides an economical, energy-efficient way for sustainable pollution control. Although single-atomic metal activation (SMA) can be exploited to optimize the pollution degradation process and understand the associated mechanisms governing IO4--based AOPs, studies on this topic are rare. Herein, we demonstrated the first instance of using SMA for IO4- analysis by employing atomically dispersed Co active sites supported by N-doped graphene (N-rGO-CoSA) activators. N-rGO-CoSA efficiently activated IO4- for organic pollutant degradation over a wide pH range without producing radical species. The IO4- species underwent stoichiometric decomposition to generate the iodate (IO3-) species. Whereas Co2+ and Co3O4 could not drive IO4- activation; the Co-N coordination sites exhibited high activation efficiency. The conductive graphene matrix reduced the contaminants/electron transport distance/resistance for these oxidation reactions and boosted the activation capacity by working in conjunction with metal centers. The N-rGO-CoSA/IO4- system exhibited a substrate-dependent reactivity that was not caused by iodyl (IO3·) radicals. Electrochemical experiments demonstrated that the N-rGO-CoSA/IO4- system decomposed organic pollutants via electron-transfer-mediated nonradical processes, where N-rGO-CoSA/periodate* metastable complexes were the predominant oxidants, thereby opening a new avenue for designing efficient IO4- activators for the selective oxidation of organic pollutants.


Evidence for two cellular pathways of renin secretion by the mouse submandibular gland.
The pathway of renin secretion has been defined in the mouse submandibular gland (SMG). Renin is first synthesized as a prorenin, rapidly cleaved to a one-chain renin, and then very slowly processed to a two-chain form which is stored in mature granules. In pulse-labeling experiments of minced SMG, the swift appearance in the culture medium of radiolabeled one-chain renin, before granule formation, suggested that this form was secreted by a constitutive pathway independent of the granules, possibly directly from the Golgi. Supporting this hypothesis, phenylephrine, which stimulates the secretion of granules, causes a 4-fold increase in the two-chain renin, with little or no effect on the secretion of one-chain renin. Confirming evidence for the existence of the constitutive pathway was provided by the action of monensin, an ionophore that inhibits transport through the Golgi. Monensin inhibited the appearance of radiolabeled newly synthesized renin in the granules and medium while causing accumulation of the newly synthesized one-chain renin in the microsomes. Analysis of secreted renin by Western blot showed that monensin selectively inhibited the secretion of one-chain renin while not affecting the secretion of the stored two-chain renin. Taken together, our data suggest that one-chain renin is primarily secreted soon after synthesis by a pathway that bypasses the granules, while two-chain renin is secreted predominantly from the granules.


Expectations of emotions during testimony: the role of communicator and perceiver characteristics.
This study investigated the influence of communicator (child victim) and perceiver (adult participant) characteristics on expectations about witnesses' emotional displays during testimony. In total, 191 adults were asked whether or not they expected child victims who were testifying about sexual abuse to display sadness, fear, anger, disgust, happiness, or a neutral demeanor, and how intensely the adults expected each emotion to be displayed. In describing the victims, child age (5 vs. 13 years old) and child gender (female vs. male) were factorially combined as within-subject factors. Results included that victim gender predicted expectations of fear, and victim age predicted expectations of anger and disgust. There was a significant interaction of victim age and victim gender for expectations of sadness. Of participants who expected multiple emotions, a combination of negative and neutral emotions was expected more from 13-year-old female victims than from 5-year-old female victims. Child victim empathy predicted ratings of how intensely sad and fearful the child victim would look. Implications of these findings for psychological research and the legal system are discussed.


Understanding the social and economic contexts surrounding women engaged in street-level prostitution.
Prostitution involves the exchange of sexual services for economic compensation. Due to the sexual promiscuity surrounding prostitution, women involved in prostitution constitute a high-risk group for contracting and transmitting STDs, including HIV. Prostitution is not only a public health concern, but also an economic one. Cities throughout the United States spent an average of $7.5 to $16 million per year enforcing prostitution laws and addressing negative outcomes associated with prostitution. Thus, women involved in prostitution are a cause for concern from both public health and economic perspectives. However, little is known about why women remain in this type of behavior given the risks prostitution presents, and even less is known about how to intervene and interrupt the complex cycle of prostitution. Thus, the purpose of this study was to understand what factors contribute to a woman's decision to remain in prostitution. A series of interviews were conducted with 12 women engaged in street-level prostitution. Results of the study revealed that drug use not only spurs entry into prostitution, but also contributes to the tenure of prostitution. Further, social support and economic stability are plausible reasons for women remaining in prostitution. These findings lead us to recommendations for policy and program development. Women involved in prostitution are a highly marginalized population, rarely recognized as individuals with life histories. Understanding why women remain in prostitution is important, because until these determinants are known, intervention programs designed to interrupt the cycle, and ultimately prevent prostitution, cannot be formulated.


Anti-idiotypic antibody response to monoclonal anti-CD4 preparations in nonhuman primate species.
A series of mouse monoclonal anti-CD4 preparations was characterized for the ability to recognize overlapping epitopes on CD4 and to inhibit HIV/simian immunodeficiency virus (SIV) syncytium formation. Based on this characterization, mAb able to recognize CD4 epitopes overlapping the HIV binding site were selected and used to immunize nonhuman primates to elicit the production of specific anti-Id antibodies. Five baboons and five rhesus monkeys were immunized with either individual or a cocktail consisting of several monoclonal anti-CD4 preparations. All the nonhuman primates produced specific anti-Id that recognized either private or cross-reactive Id depending on the monoclonal anti-CD4 used to generate the anti-Id response. Inhibition assays were performed to ascertain the ability of: 1) soluble CD4 to inhibit the Id-anti-Id reaction and 2) the various anti-Id to inhibit the CD4-monoclonal anti-CD4 reaction. These studies demonstrated that some of the anti-Id recognized a cross-reactive Id that was associated with the Ag-combining site. In addition, some of the anti-Id weakly recognized SIV gp120 by Western blot analysis. These studies may be useful in designing experiments that may lead to a better understanding of the CD4-HIV gp120 interaction and to the production of Id and/or anti-Id reagents that might be used to manipulate this virus-receptor interaction.


Colorectal Cancers: An Update on Their Molecular Pathology.
Colorectal cancers (CRCs) are the third leading cause of cancer-related mortality worldwide. Rather than being a single, uniform disease type, accumulating evidence suggests that CRCs comprise a group of molecularly heterogeneous diseases that are characterized by a range of genomic and epigenomic alterations. This heterogeneity slows the development of molecular-targeted therapy as a form of precision medicine. Recent data regarding comprehensive molecular characterizations and molecular pathological examinations of CRCs have increased our understanding of the genomic and epigenomic landscapes of CRCs, which has enabled CRCs to be reclassified into biologically and clinically meaningful subtypes. The increased knowledge of the molecular pathological epidemiology of CRCs has permitted their evolution from a vaguely understood, heterogeneous group of diseases with variable clinical courses to characteristic molecular subtypes, a development that will allow the implementation of personalized therapies and better management of patients with CRC. This review provides a perspective regarding recent developments in our knowledge of the molecular and epidemiological landscapes of CRCs, including results of comprehensive molecular characterizations obtained from high-throughput analyses and the latest developments regarding their molecular pathologies, immunological biomarkers, and associated gut microbiome. Advances in our understanding of potential personalized therapies for molecularly specific subtypes are also reviewed.


Role of an immunisation advisory clinic.
An immunisation advisory clinic was set up in Redbridge in 1984 to try to allay the anxieties of parents and doctors about vaccination against whooping cough and measles. The parents agreed to vaccination for 54 out of 67 children against whooping cough and 54 out of 57 against measles. Most of the 117 children who were referred to the clinic probably would not have been vaccinated, although only two had valid contraindications.


Improving quality of life in vasculitis patients.
Systemic vasculitis are a complex cluster of diseases with high associated morbidity. As disease-related mortality diminishes, the cumulative impact of poor health-related quality of life becomes more pertinent to patients than the initial pathological insult. In this article we explore health-related quality of life in ANCA-associated vasculitis, large-vessel vasculitis and therapeutic strategies that may enhance this critical outcome.