The role of the state in the social inclusion of complementary and alternative medical occupations.
To examine the views of government spokespersons regarding the efforts of five complementary and alternative medicine (CAM) groups (chiropractic, traditional Chinese medicine/acupuncture, naturopathy, homeopathy and Reiki) to take their place in the formal health care system. In this small scale, exploratory study, we conducted in-depth interviews with 10 key government officials at the federal (5), provincial (4) and municipal (1) levels. We used qualitative techniques such as constant comparison to describe and explain their responses to three main questions: (1) What should be the role of the state in the professionalization of CAM? (2) Is there a legitimate place for CAM groups in the formal health care system? and (3) Should CAM services be integrated with conventional medical care? Ontario, Canada. The findings identify a fundamental tension between the various levels of government. Their mandate to protect the public comes into conflict with the obligation to respond to consumer pressure for CAM. Safety, efficacy and cost-containment were the chief explanations given for the government's slowness to catch up to consumers. They also mentioned fears of rising health care costs and the lack of cohesion among and between CAM groups as barriers to legitimacy and integration. Realizing the professional aspirations of CAM practitioners will depend on the outcome of a political contest between the public, the state and the established health care professions.


Influence of the microsolvation on hemibonded and protonated hydrogen sulfide: infrared spectroscopy of [(H2S)n(X)1]+ and H+(H2S)n(X)1 (n = 1 and 2, X = water, methanol, and ethanol).
Changes of the excess charge accommodation motif in hemibonded and protonated hydrogen sulfide by microsolvation are studied by infrared spectroscopy of [(H2S)n(X)1]+ and H+(H2S)n(X)1 (n = 1 and 2, X = water, methanol, and ethanol) clusters. While the hemibond in the (H2S)2+ ion core is stable to the microhydration by a single water molecule, the hemibond is broken by the proton transfer with the microsolvation by a single methanol or ethanol molecule. Hetero hemibond formation between hydrogen sulfide and these solvent molecules is not observed. On the other hand, the excess proton in H+(H2S)n can be easily transferred to the solvent molecule, even though the proton affinity of the solvent molecule is lower than that of hydrogen sulfide. Implications of these results to the charge accommodation by sulfur under the biological conditions are discussed.


Rhodenigma contortum, an obscure new genus and species of Rhodogorgonales (Rhodophyta) from Western Australia.
An unknown microscopic, branched filamentous red alga was isolated into culture from coral fragments collected in Coral Bay, Western Australia. It grew well unattached or attached to glass with no reproduction other than fragmentation of filaments. Cells of some branch tips became slightly contorted and digitated, possibly as a substrate-contact-response seen at filament tips of various algae. Attached multicellular compact disks on glass had a very different cellular configuration and size than the free filaments. In culture the filaments did not grow on or in coral fragments. Molecular phylogenies based on four markers (rbcL, cox1, 18S, 28S) clearly showed it belongs to the order Rhodogorgonales, as a sister clade of Renouxia. Based on these results, the alga is described as the new genus and species Rhodenigma contortum in the Rhodogorgonaceae. It had no morphological similarity to either of the other genera in Rhodogorgonaceae and illustrates the unknown diversity in cryptic habitats such as tropical coral rubble.


The Hidden Burden of Outpatient Repeat PSA Testing in a Prospective Cohort.
PSA testing is widespread throughout Europe for diagnostic purposes and follow up. We performed a prospective outpatient cohort study of 250 men (2013-2015) in two hospital sites. Included were those men being followed up by urology with PSA blood testing. First appointments and those men in whom non-PSA tests were ordered by urology were excluded. The median age was 67.2yrs (46-88). Eighty-one point two percent of samples had a combination of 21 different serology tests at an added cost of >€18,000. Abnormal serology resulted in 53 referrals. Twenty-six-six percent of correspondence referenced abnormal serology other than PSA. Follow up of non-PSA test results poses a challenge in an outpatient setting with failure to appropriately follow-up on abnormal results, increased costs, and medico-legal implications. There is currently no Irish legislature in place to safeguard hospital physicians. This study quantifies the levels of expenditure, resources and risk associated with ambulant PSA testing.


The Impact of the Tumor Microenvironment on the Properties of Glioma Stem-Like Cells.
Glioblastoma is the most common and highly malignant primary brain tumor, and patients affected with this disease exhibit a uniformly dismal prognosis. Glioma stem-like cells (GSCs) are a subset of cells within the bulk tumor that possess self-renewal and multi-lineage differentiation properties similar to somatic stem cells. These cells also are at the apex of the cellular hierarchy and cause tumor initiation and expansion after chemo-radiation. These traits make them an attractive target for therapeutic development. Because GSCs are dependent on the brain microenvironment for their growth, and because non-tumorigenic cell types in the microenvironment can influence GSC phenotypes and treatment response, a better understanding of these cell types is needed. In this review, we provide a focused overview of the contributions from the microenvironment to GSC homing, maintenance, phenotypic plasticity, and tumor initiation. The interaction of GSCs with the vascular compartment, mesenchymal stem cells, immune system, and normal brain cell types are discussed. Studies that provide mechanistic insight into each of these GSC-microenvironment interactions are warranted in the future.


Ocular injection of retinal S antigen: suppression of autoimmune uveitis.
Uveoretinitis induced in Lewis rats by foot pad injections of retinal soluble (S) antigen is a model system used to study the immunopathogenesis of the autoimmune uveoretinitides in which delayed hypersensitivity plays a dominant role. Since down-regulation of delayed hypersensitivity can be achieved by injection of antigens into the anterior chamber of the eye, we have examined the potential of intracameral S antigen to mitigate experimental autoimmune uveitis. The results of these studies reveal that pretreatment of Lewis rats with S antigen injected into the anterior chamber markedly reduces the incidence and expression of experimental autoimmune uveitis.


Molecular Evolution and Phylodynamics of Acute Hepatitis B Virus in Japan.
Hepatitis B virus (HBV) is prevalent worldwide and causes liver diseases, including acute and chronic hepatitis. Ten HBV genotypes (A-J) with distinct geographic distributions have been reported. Cases of acute HBV infection with genotype A have increased in Japan nationwide since the 1990s, mainly through sexual transmission. To investigate the molecular evolution and phylodynamics of HBV genotypes, we collected acute HBV isolates acquired in Japan from 1992-2002. Full genomes were obtained for comprehensive phylogenetic and phylodynamic analysis, with other Japanese HBV sequences from GenBank that were isolated during 1991-2010. HBV genotypes were classified using the maximum-likelihood and Bayesian methods. The GMRF Bayesian Skyride was used to estimate the evolution and population dynamics of HBV. Four HBV genotypes (A, B, C, and H) were identified, of which C was the major genotype. The phylodynamic results indicated an exponential growth between the 1960s and early 1990s; this was followed by a population bottleneck after 1995, possibly linked with successful implementation of a nationwide vaccination program. However, HBV/A increased from 1990 to 2003-2004, and then started to decrease. The prevalence of genotype A has increased over the past 10 years. Phylodynamic inference clearly demonstrates a steady population growth compatible with an ongoing subepidemic; this might be due to the loss of immunity to HBV in adolescents and people being born before the vaccination program. This is the first phylodynamic study of HBV infection in Japan and will facilitate understanding the molecular epidemiology and long-term evolutionary dynamics of this virus in Japan.


Function of plastidial pyruvate kinases in seeds of Arabidopsis thaliana.
Pyruvate kinase (PK) catalyses the irreversible synthesis of pyruvate and ATP, which are both used in multiple biochemical pathways. These compounds are essential for sustained fatty acid production in the plastids of maturing Arabidopsis embryos. Using a real-time quantitative reverse transcriptase (RT)-PCR approach, the three genes encoding putative plastidial PKs (PKps) in Arabidopsis, namely PKp1 (At3g22960), PKp2 (At5g52920) and PKp3 (At1g32440), were shown to be ubiquitously expressed. However, only PKp1 and PKp2 exhibited significant expression in maturing seeds. The activity of PKp1 and PKp2 promoters was consistent with this pattern, and the study of the PKp1:GFP and PKp2:GFP fusion proteins confirmed the plastidial localization of these enzymes. To further investigate the function of these two PKp isoforms in seeds comprehensive functional analyses were carried out, including the cytological, biochemical and molecular characterization of two pkp1 and two pkp2 alleles, together with a pkp1pkp2 double mutant. The results obtained outlined the importance of these PKps for fatty acid synthesis and embryo development. Mutant seeds were depleted of oil, their fatty acid content was drastically modified, embryo elongation was retarded and, finally, seed germination was also affected. Together, these results provide interesting insights concerning the carbon fluxes leading to oil synthesis in maturing Arabidopsis seeds. The regulation of this metabolic network by the WRINKLED1 transcription factor is discussed, and emphasizes the role of plastidial metabolism and the importance of its tight regulation.


EXIA2: web server of accurate and rapid protein catalytic residue prediction.
We propose a method (EXIA2) of catalytic residue prediction based on protein structure without needing homology information. The method is based on the special side chain orientation of catalytic residues. We found that the side chain of catalytic residues usually points to the center of the catalytic site. The special orientation is usually observed in catalytic residues but not in noncatalytic residues, which usually have random side chain orientation. The method is shown to be the most accurate catalytic residue prediction method currently when combined with PSI-Blast sequence conservation. It performs better than other competing methods on several benchmark datasets that include over 1,200 enzyme structures. The areas under the ROC curve (AUC) on these benchmark datasets are in the range from 0.934 to 0.968.


Long-term preservation of freeze-dried rabbit sperm by adding rosmarinic acid and different chelating agents.
Freeze-drying (FD) technique has been applied as an alternative technology to preserve gene resources to allow simple sperm preservation and shipment at 4 °C. Nevertheless, DNA sperm might be damaged by mechanical or oxidative stress throughout FD procedure. Therefore, suitable protection to maintain DNA integrity is required. The aim of this study was to determine the effect of rosmarinic acid (RA) as an antioxidant and two chelating agents (EGTA and EDTA) on the DNA integrity of freeze-dried rabbit sperm after storage of the samples at 4 °C and room temperature for 8 months. Rabbit sperm were freeze-dried in basic medium (10 mM Tris-HCl buffer and 50 mM NaCl) supplemented with 50 mM EGTA (1), 50 mM EGTA plus 105 μM RA (2), 50 mM EDTA (3) or 50 mM EDTA plus 105 μM RA (4). Semen samples were kept at 4 °C and room temperature during 8 months. After rehydration, DNA integrity was evaluated with Sperm Chromatin Dispersion test observing that DNA fragmentation was higher when semen samples were freeze-dried with EGTA (10.9%) than with EDTA (4.1%) (p < 0.01). Furthermore, RA acted better under adverse conditions and no significant differences were found in temperature storage. Summarizing, FD is a method that can allow simple gene resources preservation among 4 °C to 25 °C during 8 months and transportation without the need for liquid nitrogen or dry ice. EDTA chelating agent is the most suitable media for freeze-dried rabbit sperm and the addition of RA protects the DNA against the oxidative stress caused during FD procedure.


Nuclease activity of Saccharomyces cerevisiae Mre11 functions in targeted nucleotide alteration.
Oligonucleotides can be used to direct site-specific changes in genomic DNA through a process in which mismatched base pairs in the oligonucleotide and the target DNA are created. The mechanism by which these complexes are developed and resolved is being studied by using Saccharomyces cerevisiae as a model system. Genetic analyses have revealed that in all likelihood the reaction occurs in two phases: DNA pairing and DNA repair. While the former phase involves strand assimilation, the latter phase likely involves an endonucleolytic processing step that leads to joint resolution. In this study, we established the importance of a functioning MRE11 gene in the overall reaction, as yeast strains deficient in MRE11 exhibited severely reduced activity. The activity could be rescued by complementation with wild-type MRE11 genes but not with MRE11 alleles lacking the nuclease function. Taken together, the data suggest that Mre11 provides nuclease activity for targeted nucleotide exchange, a process that could be used to reengineer yeast genes.


Discrepancies between explicit and implicit review: physician and nurse assessments of complications and quality.
To identify and characterize discrepancies between explicit and implicit medical record review of complications and quality of care. Forty-two acute-care hospitals in California and Connecticut in 1994. In a retrospective chart review of 1,025 Medicare beneficiaries age >65, we compared explicit (nurse) and implicit (physician) reviews of complications and quality in individual cases. To understand discrepancies, we calculated the kappa statistic and examined physicians' comments. With Medicare discharge abstracts, we used the Complications Screening Program to identify and then select a stratified random sample of cases flagged for 1 of 15 surgical complications, 5 medical complications, and unflagged controls. Peer Review Organization nurses and physicians performed chart reviews. Agreement about complications was fair (kappa = 0.36) among surgical and was moderate (kappa = 0.59) among medical cases. In discordant cases, physicians said that complications were insignificant, attributable to a related diagnosis, or present on admission. Agreement about quality was poor among surgical and medical cases (kappa = 0.00 and 0.13, respectively). In discordant cases, physicians said that quality problems were unavoidable, small lapses in otherwise satisfactory care, present on admission, or resulted in no adverse outcome. We identified many discrepancies between explicit and implicit review of complications and quality. Physician reviewers may not consider process problems that are ubiquitous in hospitals to represent substandard quality.


Bioaccumulation and metabolomics responses in oysters Crassostrea hongkongensis impacted by different levels of metal pollution.
Jiulong River Estuary, located in southern China, was heavily contaminated by metal pollution. In this study, the estuarine oysters Crassostrea hongkongensis were transplanted to two sites with similar hydrological conditions but different levels of metal pollution in Jiulong River Estuary over a six-month period. We characterized the time-series change of metal bioaccumulation and final metabolomics responses of oysters. Following transplantation, all metals (Cd, Cu, Cr, Ni, Pb, and Zn) in the oyster digestive glands had elevated concentrations over time. By the end of six-month exposure, Cu, Zn and Cd were the main metals significantly differentiating the two sites. Using (1)H NMR metabolite approach, we further demonstrated the disturbance in osmotic regulation, energy metabolism, and glycerophospholipid metabolism induced by metal contaminations. Six months later, the oysters transplanted in the two sites showed a similar metabolite variation pattern when compared with the initial oysters regardless of different metal levels in the tissues. Interestingly, by comparing the oysters from two sites, the more severely polluted oysters accumulated significantly higher amounts of osmolytes (betaine and homarine) and lower energy storage compounds (glycogen) than the less polluted oysters; these changes could be the potential biomarkers for different levels of metal pollution. Our study demonstrated the complexity of biological effects under field conditions, and NMR metabolomics provides an important approach to detect sensitive variation of oyster inner status.


Does co-inoculation of Lactuca serriola with endophytic and arbuscular mycorrhizal fungi improve plant growth in a polluted environment?
Phytoremediation of polluted sites can be improved by co-inoculation with mycorrhizal and endophytic fungi. In this study, the effects of single- and co-inoculation of Lactuca serriola with an arbuscular mycorrhizal (AM) fungus, Rhizoglomus intraradices, and endophytic fungi, Mucor sp. or Trichoderma asperellum, on plant growth, vitality, toxic metal accumulation, sesquiterpene lactone production and flavonoid concentration in the presence of toxic metals were evaluated. Inoculation with the AM fungus increased biomass yield of the plants grown on non-polluted and polluted substrate. Co-inoculation with the AM fungus and Mucor sp. resulted in increased biomass yield of plants cultivated on the polluted substrate, whereas co-inoculation with T. asperellum and the AM fungus increased plant biomass on the non-polluted substrate. In the presence of Mucor sp., mycorrhizal colonization and arbuscule richness were increased in the non-polluted substrate. Co-inoculation with the AM fungus and Mucor sp. increased Zn concentration in leaves and roots. The concentration of sesquiterpene lactones in plant leaves was decreased by AM fungus inoculation in both substrates. Despite enhanced host plant costs caused by maintaining symbiosis with numerous microorganisms, interaction of wild lettuce with both mycorrhizal and endophytic fungi was more beneficial than that with a single fungus. The study shows the potential of double inoculation in unfavourable environments, including agricultural areas and toxic metal-polluted areas.


Lexical competition and phonological encoding in young and older speakers.
The influence of age on word retrieval was investigated with a speeded picture naming study. Five hundred forty-one pictures were presented to young and older adults, and the influence of name agreement and name frequency was analyzed by multiple regression. The results showed that both name agreement and name frequency are significant predictors of picture naming performance in young and older adults. The results also suggest that older adults are more strongly influenced by name agreement than are young adults. These results indicate that competition during lexical selection may be a particularly age-sensitive stage in language production.


The effect of interferon gamma on conventional fractionated radiation-induced damage and fibrosis in the pelvic tissue of rabbits.
We aim to investigate the effect of interferon gamma (IFN-γ) on conventional fractionated radiation-induced damage and fibrosis in ureter and colorectal mucosa. Fifty-two rabbits were randomly divided into three groups comprising a conventional radiation group, an IFN-γ group, and a control group. X-rays were used to irradiate the pelvic tissues of the rabbits in the IFN-γ and conventional radiation groups. Five days after radiation exposure, the rabbits in the IFN-γ group were administered 250,000 U/kg IFN-γ intramuscularly once a week for 5 weeks. The rabbits in the conventional radiation group received 5.0 mL/kg saline. The rabbits were sacrificed at 4, 8, 12, and 16 weeks postradiation, and the rectal and ureteral tissues within the radiation areas were collected. The results showed that the morphology of rectal and ureteral tissues was changed by X-ray radiation. The degree of damage at 4, 8, and 12 weeks, but not at 16 weeks, postradiation was significantly different between the IFN-γ and conventional radiation groups. The expression of transforming growth factor beta 1 mRNA in the ureter and colorectal mucosa of the IFN-γ group was significantly lower than that in the conventional radiation group at 4, 8, 12, and 16 weeks postradiation, but it was still higher than that in the control group. There were significant differences in the expression of collagen III among the three groups. IFN-γ can inhibit the radiation-induced upregulation of transforming growth factor beta 1 mRNA and collagen III protein in the ureter and colorectal mucosa and attenuate radiation-induced damage and fibrosis.


Noradrenergic tone mediates marble burying behavior after chronic stress and ethanol.
Stress plays a major role in the development of alcohol use disorder (AUD)-a history of chronic stress contributes to alcohol misuse, and withdrawal from alcohol elevates stress, perpetuating cycles of problematic drinking. Recent studies have shown that, in male mice, repeated chronic intermittent ethanol (CIE) and stress elevates alcohol use above either manipulation alone and impacts cognitive functions such as behavioral flexibility. Here, we investigated the impact of CIE and stress on anxiety in both sexes, and whether the norepinephrine (NE) system via locus coeruleus, which is implicated in both stress and alcohol motivation, is involved. Male and female mice received multiple cycles of CIE and/or repeated forced swim stress (FSS), producing elevated drinking in both sexes. CIE/FSS treatment increased anxiety, which was blocked by treatment with the α1-AR inverse agonist prazosin. In contrast, administration of the corticotropin releasing factor receptor antagonist CP376395 into locus coeruleus did not reduce CIE/FSS-elevated anxiety. We also observed sex differences in behavioral responses to a history of CIE or FSS alone as well as differential behavioral consequences of prazosin treatment. These data indicate that NE contributes to the development of anxiety following a history of alcohol and/or stress, and that the influence of both treatment history and NE signaling is sex dependent. These results argue for further investigation of the NE system in relation to disrupted behavior following chronic alcohol and stress, and support the assertion that treatments may differ across sex based on differential neural system engagement.


Epigallocatechin-3-Gallate (EGCG) Reduces Rotenone Effect on Stallion Sperm-Zona Pellucida Heterologous Binding.
Stallion spermatozoa are highly dependent on oxidative phosphorylation for ATP production to achieve normal sperm function and to fuel the motility. The aim of this study was to evaluate the response of equine sperm under capacitating conditions to the inhibition of mitochondrial complex I by rotenone and to test whether epigallocatechin-3-gallate (EGCG), a natural polyphenol component of green tea, could counteract this effect. After 2-h incubation of stallion spermatozoa in modified Tyrode's medium, rotenone (100 nm, 500 nm and 5 μm) and EGCG (10, 20 and 60 μm), alone or in combination, did not induce any significant difference on the percentage of viable cells, live sperm with active mitochondria and spermatozoa with intact acrosome. The inhibition of complex I of mitochondrial respiratory chain of stallion sperm with rotenone exerted a negative effect on heterologous ZP binding ability. EGCG at the concentrations of 10 and 20 μm (but not of 60 μm) induced a significant increase in the number of sperm bound to the ZP compared with that for control. Moreover, when stallion sperm were treated with rotenone 100 nm, the presence of EGCG at all the concentrations tested (10, 20 and 60 μm) significantly increased the number of sperm bound to the ZP up to control levels, suggesting that this green tea polyphenol is able to reduce the toxicity of rotenone.


Current knowledge and recent development on management of peripartum cardiomyopathy.
Heart failure with left ventricular dysfunction occurring during pregnancy or during the post-partum period in patients without history of cardiovascular disease defines peripartum cardiomyopathy (PPCM). PPCM carries a high morbidity and mortality rate as well as the possibility of recovery ad integrum. Its incidence shows ethnic variations, with a greater prevalence of the disease among women with African descent. Pathogenesis of PPCM remains poorly understood. Both "oxidative stress-prolactin axis" and "anti-angiogenic-signaling excess" hypotheses are currently being investigated. Novel diagnostic strategies and biomarkers are currently being evaluated. Besides conventional treatment of heart failure, targeted therapies such as pharmacological prolactin blockade are under evaluation. The aim of this short review is to highlight current management as targeted therapy has far been disappointing.


Geometric entangling gates in decoherence-free subspaces with minimal requirements.
We introduce a new strongly driven dispersive atom-cavity interaction and develop a new scheme for implementing the nontrivial entangling gates for two logical qubits in decoherence-free subspaces (DFSs). Our scheme combines the robust advantages of DFS and the geometric phase. Moreover, only two neighboring physical qubits, which encode a logical qubit, are required to undergo the collective dephasing in our scheme.


Development of neurosurgery in Canada.
The development of neurosurgery in Canada is traced through an analysis of the contributions of key early figures in this specialty. The evolution of Canadian training standards is discussed against the background of socio-economic change in the nation at large.


Characteristics and clinical outcomes of COVID-19 patients in an underserved-inner city population: A single tertiary center cohort.
There is limited information describing the characteristics and clinical outcomes of patients infected with coronavirus disease 2019 (COVID-19) especially those in underserved urban area with minority population in the United States. This is a retrospective single-center study for patients who were admitted with COVID-19 infection. Data collection was from 1 March through 24 April 2020. Demographic, clinical, laboratory, and treatment data were presented using descriptive statistics and frequencies. The χ2 test and multivariate logistic regression were used to determine association of risk factors and clinical outcomes. A total of 242 inpatients were included with a mean age of 66 ± 14.75 (±standard deviation). A total of 50% were female and 70% were African American. Comorbidities included hypertension (74%), diabetes mellitus (49%), and 19% had either COPD or asthma. Older age was associated with higher risk of inpatient death odds ratio (OR): 1.056 (95% confidence interval [CI]: 1.023-1.090; P = .001). Inpatient mortality occurred in 70% who needed mechanical ventilation (OR: 29.51; 95% CI: 13.28-65.60; P < .0001), 58% who required continuous renal replacement therapy/hemodialysis (CRRT/HD) (OR: 6.63; 95% CI: 2.74-16.05; P < .0001), and 69% who needed vasopressors (OR: 30.64; 95% CI: 13.56-69.20; P < .0001). Amongst biomarkers of disease severity, only baseline CRP levels (145 ± 116 mg/L) were associated with mortality OR: 1.008 (95% CI: 1.003-1.012; P = .002). Majority of hospitalized patients had hypertension and diabetes. Older age was an independent risk factor for inpatient mortality. Requirement of mechanical ventilation, vasopressor use, and CRRT/HD was associated significantly with inpatient mortality. Higher baseline CRP was significantly associated with inpatient death.


Management of adults recovering from alcohol or other drug problems: relapse prevention in primary care.
Patients recovering from substance use disorders are commonly seen in the primary care setting, and relapse is a serious long-term problem for these patients. Extrapolating from therapeutic strategies effective in specialty addiction treatment settings, this article outlines a practical approach to relapse prevention in the primary care setting. Working within a supportive patient-physician relationship, the primary care physician can help recovering patients decrease their susceptibility to relapse, recognize and manage high-risk situations, and use available self-help, pharmacological, and specialty resources. Drawing on the therapeutic relationship and skills they already possess, primary care physicians can have an important, productive, and satisfying role in the long-term management of patients in recovery from alcohol or other drug problems.


Sarcopenia and risk of cardio-cerebrovascular disease: A two-sample Mendelian randomization study.
Based on the association between sarcopenia and the risk of developing cardio-cerebrovascular disease (CCVD) established by a meta-analysis by Fang et al.(Biosci Trends. 2023; 17:293-301), we have used Mendelian randomization (MR) analysis to test the authenticity and accuracy of such an association. In this MR study, appendicular lean mass, handgrip strength, and walking pace were used as sarcopenia-related traits, with cardiovascular diseases and stroke set as outcomes of CCVD. MR analysis was performed using inverse-variance weighting, the MR Egger, weighted median, simple mode, and weighted mode. No heterogeneity or horizontal pleiotropy in MR estimates was observed (Cochran's Q P value > 0.05, MR-PRESSO global test P value > 0.05, and MR-Egger intercept P value > 0.05). Results of that analysis proved a causal relationship between sarcopenia-related traits and cardio-cerebrovascular disease, with a causal association between appendicular lean mass and cardiovascular diseases and an inverse causal relationship between appendicular lean mass and stroke. However, such a relationship was absent in the case of handgrip strength and the risk of cardiovascular diseases as well as in the case of walking pace and lacunar/ischemic stroke. Therefore, the effect of sarcopenia on CCVD should be carefully explained.


Drug targeted virtual screening and molecular dynamics of LipU protein of Mycobacterium tuberculosis and Mycobacterium leprae.
The lipolytic protein LipU was conserved in mycobacterium sp. including M. tuberculosis (MTB LipU) and M. leprae (MLP LipU). The MTB LipU was identified in extracellular fraction and was reported to be essential for the survival of mycobacterium. Therefore to address the problem of drug resistance in pathogen, LipU was selected as a drug target and the viability of finding out some FDA approved drugs as LipU inhibitors in both the cases was explored. Three-dimensional (3D) model structures of MTB LipU and MLP LipU were generated and stabilized through molecular dynamics (MD). FDA approved drugs were screened against these proteins. The result showed that the top-scoring compounds for MTB LipU were Diosmin, Acarbose and Ouabain with the Glide XP score of -12.8, -11.9 and -11.7 kcal/mol, respectively, whereas for MLP LipU protein, Digoxin (-9.2 kcal/mol), Indinavir (-8.2 kcal/mol) and Travoprost (-8.2 kcal/mol) showed highest affinity. These drugs remained bound in the active site pocket of MTB LipU and MLP LipU structure and interaction grew stronger after dynamics. RMSD, RMSF and Rg were found to be persistent throughout the simulation period. Hydrogen bonds along with large number of hydrophobic interactions stabilized the complex structures. Binding free energies obtained through Prime/MM-GBSA were found in the significant range from -63.85 kcal/mol to -34.57 kcal/mol for MTB LipU and -71.33 kcal/mol to -23.91 kcal/mol for MLP LipU. The report suggested high probability of these drugs to demolish the LipU activity and could be probable drug candidates to combat TB and leprosy disease.


Repeated determinants within the retinal interphotoreceptor retinoid-binding protein (IRBP): immunological properties of the repeats of an immunodominant determinant.
Interphotoreceptor retinoid-binding protein (IRBP), a glycoprotein which localizes in the retina and pineal gland, induces inflammatory changes in these organs (EAU and EAP, respectively) when injected into various mammals. We have previously identified a determinant (residues 1169-1191) in bovine IRBP which is immunodominant and highly immunogenic and immunopathogenic in Lewis rats. IRBP exhibits a fourfold repeat structure and we report here on the comparison between the active sequence 1179-1191 and its three repeat peptides. Only one of the repeats, 271-283, cross-reacted with 1179-1191 and exhibited immunodominance, albeit of a low level. Peptide 271-283 was also immunogenic and immunopathogenic in Lewis rats, but with a minimal dose approximately 100 times higher than that of 1179-1191. Peptide 880-892, a nondominant determinant, resembled 271-283 in its immunogenicity, but was markedly less immunopathogenic. No immunological activity was detected in the fourth repeat peptide, 579-591. Peptide 1179-1191 was superior to the other repeats also in its antigenicity, i.e., the capacity to stimulate presensitized lymphocytes in culture: the minimal stimulatory concentrations of 1179-1191 was greater than 1000 times lower than those of 271-283 or 880-892. Furthermore, 1179-1191 was stimulatory at concentrations lower than those of 271-283 even when tested with lymphocytes sensitized against 271-283. A correlation was also found between the immunological activities of the repeat peptides and their amphipathicity. This study thus identifies two new immunopathogenic determinants of IRBP and provides additional data to show the association between immunodominance of peptides and their various immunological activities.


Tip-modulation scanned gate microscopy.
We introduce a technique that improves the sensitivity and resolution and eliminates the nonlocal background of scanned gate microscopy (SGM). In conventional SGM, a voltage bias is applied to the atomic force microscope tip and the sample conductance is measured as the tip is scanned. In the new technique, which we call tip-modulation SGM (tmSGM), the biased tip is oscillated and the induced oscillation of the sample conductance is measured. Applied to single-walled carbon nanotube network devices, tmSGM gives sharp, low-noise and background-free images.


Progressive cytochrome c oxidase deficiency in a case of Kearns-Sayre syndrome: morphological, immunological, and biochemical studies in muscle biopsies and autopsy tissues.
We report biochemical, immunological, and morphological findings in a patient with fatal Kearns-Sayre syndrome. Histochemical and biochemical findings from muscle biopsy specimens obtained 7 years apart documented the disease's evolution from a mild mitochondrial disorder affecting a small proportion of muscle fibers to a severe disorder affecting a large proportion of muscle fibers. Cytochrome c oxidase activity in muscle declined profoundly as the disease progressed, although the level of enzyme protein was normal, as shown by immunochemical techniques. Other organs were severely affected by the disease. Examination of postmortem tissue showed spongiosis in the frontal cortex, diffuse loss of Purkinje cells in the cerebellum, liver steatosis, and heart fibrosis with mitochondrial abnormalities. Cytochrome c oxidase activity was only slightly reduced in these organs.


Hepatic urea biosynthesis in the euryhaline elasmobranch Carcharhinus leucas.
Plasma urea levels and hepatic urea production in the euryhaline bull shark, Carcharhinus leucas, acclimated to freshwater and seawater environments were measured. It was found that plasma urea concentration increased with salinity and that this increase was, in part, the result of a significant increase in hepatic production of urea. This study provides direct evidence that hepatic production of urea plays an important role in the osmoregulatory strategy of C. leucas.


Protective Effect of Met12, a Small Peptide Inhibitor of Fas, on the Retinal Pigment Epithelium and Photoreceptor After Sodium Iodate Injury.
A major problem in macular degeneration is the inability to reduce RPE and photoreceptor death. These cells die by necroptosis and apoptosis, respectively, but the upstream activator(s) of these death pathways is unknown. In this study, we use the sodium iodate (NaIO3) model of oxidative stress to test the hypothesis that activation of the Fas receptor contributes to the death of the RPE and photoreceptors. Sodium iodate was injected in Brown-Norway rats via femoral vein injection. Both in vivo (fundus photography, optical coherence tomography, and fluorescein angiography) and ex vivo (histology, immunohistochemistry, Western blot, and RT-PCR) analyses of the RPE and retina were conducted at baseline, as well as at various times post NaIO3 injection. The ability of intravitreal injection of Met12, a small peptide inhibitor of the Fas receptor, to prevent RPE and photoreceptor cell death was assessed. Injection of NaIO3 led to Fas-mediated activation of both necroptosis and apoptosis in the RPE and photoreceptors, respectively. This was accompanied by a significant increase in the number of microglia/macrophages in the outer retina. Met12 significantly reduced the activation of the Fas-mediated death pathways, resulting in reduced RPE and photoreceptor death and a decreased immune response. Our results demonstrate that NaIO3 activates Fas-mediated cell death, both in the RPE and photoreceptor, and that a small peptide antagonist of the Fas receptor, Met12, significantly reduces the extent of this cell death. These findings suggest a role for Fas inhibition to protect the RPE and photoreceptors from death due to oxidative stress.


Regeneration of the semitendinosus tendon after its harvesting for anterior cruciate ligament reconstruction.
The semitendinosus muscle has a unique anatomical structure. Its long and strong distal tendon is frequently selected as a material for autogenous grafts in anterior cruciate ligament reconstruction. The article provides an overview of literature concerning the little known process of spontaneous regeneration of the semitendinosus tendon after its harvesting. Subsequent to harvesting, the muscle devoid of its distal tendon demonstrates regeneration potential. It sends an outgrowth which is structurally very similar to the original tendon. This process is observed in the majority of patients. This tendon-like structure usually attaches to fascial structures below the knee joint. There are suggestions that partial functional recovery of the muscle from which the tendon has been harvested is possible.


United States Department of Agriculture nutrition assistance programs during the COVID-19 pandemic: A scoping review protocol.
The goal of this scoping review is to examine the published research on federal nutrition assistance programs administered by the United States (U.S.) Department of Agriculture during the COVID-19 pandemic, in the U.S., U.S. territories, and tribal nations. The review will identify the scope of the available research and provide research and policy recommendations. The COVID-19 pandemic made individuals more vulnerable to experiencing food insecurity. Federal nutrition assistance programs help to address food insecurity and have been rapidly adapting to meet food and nutrition needs among affected communities during the COVID-19 pandemic. It is important to understand the scope of the current research on this topic to help inform future research, practice, and policy recommendations. This review will include studies focused on federal nutrition assistance programs administered by the U.S. Department of Agriculture during the COVID-19 pandemic. The scoping review will consider all primary research designs. Pubmed, CINHAL, Scopus, and Proquest's Health Management databases will be used for the literature search. Only articles published in English since March 1, 2020 will be considered. Titles/abstracts followed by full-text articles will be reviewed to determine which articles meet the inclusion criteria and should be included in the review. Data will be extracted from each included article using a data extraction template in Covidence that will be developed by the study team. Data extracted will include information on key findings related to the review questions. At each step, two independent reviewers will be assigned to each article. Data will be summarized and presented in tables, charts, and narrative summary.


Antiausterity agents from Uvaria dac and their preferential cytotoxic activity against human pancreatic cancer cell lines in a nutrient-deprived condition.
Human pancreatic cancer cell lines are known for their inherent tolerance to nutrition starvation, which enables them to survive under a hypovascular (austerity) tumor microenvironment. The search for agents that preferentially retard the survival of cancer cells under low nutrition conditions (antiausterity agent) is a novel approach to anticancer drug discovery. In this study, it was found that a dichloromethane extract of the stem of Uvaria dac preferentially inhibited PANC-1 human pancreatic cancer cells survival under nutrition-deprived conditions at a concentration of 10 μg/mL. Workup of this bioactive extract led to the discovery of (+)-grandifloracin (8) as a potent antiausterity agent as evaluated in a panel of four human pancreatic cancer cell lines, PANC-1 (PC(50), 14.5 μM), PSN-1 (PC(50), 32.6 μM), MIA PaCa-2 (PC(50), 17.5 μM), and KLM-1 (32.7 μM). (+)-Grandifloracin (8) has been isolated from a natural source for the first time. Its absolute stereochemistry was established by single-crystal X-ray crystallography and circular dichroism spectroscopic analysis. In addition to this, seven other new highly oxygenated cyclohexene derivatives, named uvaridacanes A (1) and B (2), uvaridacols A-D (3, 4, 6, 7), and uvaridapoxide A (5), were also isolated and structurally characterized.


Virus-Based RNA Silencing Agents and Virus-Derived Expression Vectors as Gene Therapy Vehicles.
In consideration of recent developments in understanding the genomics and proteomics of viruses, the use of viral DNA / RNA sequences as well as their gene expression schemes, have found new in-roads towards the prognosis and therapy of diseases. Correspondingly, the sphere of the patenting scenario has expanded significantly. The current review addresses patented inventions concerning the use of virus sequences as gene silencing machineries and inventions concerning the generation and application of viral sequences as expression vectors. Furthermore, this review also discusses the employment of these patents for clinical, agricultural and biotechnological applications. Considering these objectives, the Delphion Research Intellectual Property Network database was searched using keywords such as "gene silencing", "engineered viruses" and "expression vectors" and descriptions of recent patents on the said topics were discussed. Despite several recent advances in the use of viruses as disease therapy vehicles and biotechnological vectors, these developments have yet to be proven effective in practice, in clinical and field trials.


Extrachromosomal DNA and its activity in RNA synthesis in oogonia and oocytes in the pupal ovary of Creophilus maxillosus (Staphylinidae, Coleoptera-Polyphaga).
The participation of extrachromosomal DNA (extra DNA) in RNA synthesis in the nuclei of terminal oogonial cells and oocytes in the pupal ovary of Creophilus maxillosus (Staphylinidae, Coleoptera) was examined by autoradiography. It was found that extra DNA in the nuclei of terminal oogonial cells, although predominantly in a condensed and heterochromatic state, produces numerous nucleoli and incorporates 3H-uridine during the interphases between successive differential divisions. Moreover, it was shown that extra DNA is active in RNA synthesis at the same stage of pupal development in which it is synthesized and accumulated, i.e. in the nuclei of terminal oogonial cells. As soon as the oocyte forms RNA synthesis ceases in the extrachromosomal DNA body cells showed that nucleolar material does not disappear during division but remains, at least partly, connected with the extra DNA body.


Population pharmacokinetics and pharmacodynamics of pyridostigmine bromide for prophylaxis against nerve agents in humans.
This study was conducted to determine the pharmacokinetics and pharmacodynamics of pyridostigmine given as 30 mg of pyridostigmine bromide every 8 hours in healthy subjects. Plasma pyridostigmine concentration and red blood cell acetylcholinesterase activity were measured in blood samples collected during a 3-week period. Population analysis was performed using standard pharmacokinetic and pharmacodynamic models with the nonlinear mixed-effect modeling software (NONMEM). The pharmacokinetic model that best fit the pyridostigmine plasma levels was a two-compartment open model with first-order absorption, a lag time, and first-order elimination from the central compartment. The pharmacodynamic model that best fit red blood cell acetylcholinesterase activity was an inhibitory Emax model with an effect compartment linked to the central compartment. The results showed that the pharmacokinetics of pyridostigmine bromide are both gender and weight dependent. The pharmacodynamic effect does not lag significantly from the plasma concentration and returns to near normal within 8 hours. With the present dosage regimen of 30 mg every 8 hours, 30% of individuals may not have red blood cell acetylcholinesterase inhibition > 10% at the time of the trough.


Reproductive ageing, sex steroids and depression.
Perimenopausal depression affects a considerable number of women and is associated with significant disability and morbidity. Major and minor depressions are the two most prevalent forms of acute depressive illness. Major depression has an estimated lifetime prevalence of 17% and affects approximately twice as many women as men. While the relationship between the onset of depressive illness and reproductive senescence is controversial, epidemiological and clinic-based studies that have distinguished between the perimenopause and the postmenopause have documented that, for some middle-aged women, the perimenopause is associated with an increased vulnerability to depression. Future studies of perimenopausal depression should identify the number of women affected, individual risk factors and the role of hormonal therapies in this condition.


A sampling strategy for qualitative research.
This paper discusses sampling in qualitative research, describing the principles and how different researchers have described their sampling techniques. The example of a research project in which the authors were involved ( 1 ) is used to show how a range of quantitative and qualitative sampling techniques can be combined, highlighting some of the problems. In particular, where theoretical sampling was required, we found that a systematic way of identifying theoretically useful sampling units was needed, and so a method of selection which we have called matrix sampling was devised, whereby informed and coherent choices could be made.


The dynamics of a Chinese porcine G9P[23] rotavirus production in MA-104 cells and intestines of 3-day-old piglets.
Rotavirus A (RVA) G9 genotype is recognized as an emerging genotype which is spreading worldwide, however, our knowledge on pathogenicity of this virus is limited. In this study, porcine RVA strain HN03 was successfully isolated on MA-104 cells, and the isolate was propagated continuously for 7 passages after a virus cloning at passage 3. The virus titers from 4 to 10 passages ranged from 107.1 to 108.1 TCID50/ml. The growth curve of HN03 strain in cell culture was determined, and the virus production dynamics was confirmed by immunoperoxidase monolayer assay (IPMA). Sequence and phylogenetic analyses based on full-length VP7 and partial VP4 genes indicated that HN03 strain belongs to genotype G9P[23]. In addition, the sixth passage of strain HN03 in cell culture was subjected to 3-day-old piglets. All infected piglets developed severe watery diarrhea within 24 hr post-inoculation (hpi), but recovered from disease after 72 hpi. RVA antigen could be detected by IHC in the cytoplasm of villous enterocytes as early as 2 hr after appearance of clinical symptoms and virus antigen load kept increasing in the next 30 hr. The dynamics of RVA HN03 strain proliferation on cells and in pigs extended our understanding of rotavirus pathogenicity.


A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study.
A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100 mm × 2.1 mm, 5 µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5⁻1000 ng/mL range. The intra- and inter-day precisions for nimbolide were ≤12.6% and ≤13.9% respectively. Intra-day accuracy ranged from 96.9⁻109.3%, while inter-day accuracy ranged from 94.3⁻110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum, and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy.


Vitamins and carotenoids intake and the risk of basal cell carcinoma of the skin in women (United States).
We examined prospectively intakes of vitamins A. C, and E, folate, and specific carotenoids in relation to the risk of basal cell carcinoma of the skin (BCC) in women. Dietary intake was assessed by food-frequency questionnaires every two-four years and the first diagnosis of BCC was ascertained by self-report every two years. We used logistic regression to model the association between dietary intake and the risk of BCC adjusting for various health, sun exposure, and sun sensitivity factors. During 12 years of follow-up we recorded 5392 cases. We did not find any significant inverse associations between these dietary factors and BCC. On the contrary. weak positive trends were seen with vitamins A, C, and E, and folate. The multivariate relative risks (RRs) comparing the top to bottom quintile were 1.20 (95% CI = 1.10-1.31) for folate, 1.16 (95% CI = 1.06-1.26) for vitamin A. 1.13 (95% CI = 1.03-1.23) for vitamin C, and 1.15 (95% CI = 1.06-1.26) for vitamin E. Exploration of latency periods did not suggest different associations with a particular duration. We did not find evidence that vitamins A, C, and E. and folate. or specific carotenoids play an important protective role against the incidence of BCC.


Sleep problems among women with noncancerous gynecologic conditions.
To estimate the prevalence of and identify factors associated with poor sleep quality and short sleep duration among women with noncancerous gynecologic conditions. We conducted a cross-sectional analysis of 838 pre-menopausal women aged 31-54 who enrolled in a study of pelvic problems, hysterectomy and intervention alternatives in 2003/2004. Primary outcomes were poor sleep quality and short sleep duration (six or less hours on average) in the four weeks preceding the interview; hypothesized correlates included sociodemographic characteristics, pelvic problem impact, measured by the Pelvic Problem Impact Questionnaire (PPIQ), and depression, measured by the Patient Health Questionnaire (PHQ). One-third (33.7%) of the participants reported having poor sleep quality and nearly half (46.8%) reported short sleep duration. In multivariable models, women with major depressive disorder were more likely than those who were not depressed to experience poor sleep quality (adjusted odds ratio (aOR) 4.15, 95% confidence interval (CI) 2.36-7.28, p < 0.001). Women with higher PPIQ scores also were more likely to experience poor sleep quality (aOR 1.59, 95% CI 1.27-1.98, p < 0.001) and short sleep duration (aOR 1.37, 95% CI 1.11-1.69, p < 0.003). Finally, women who self-identified as African-American (aOR 2.81, 95% CI 1.83-4.32, p < 0.001) or Asian/Pacific Islander (aOR 2.32, 95% CI 1.32-4.09, p < 0.003) were more likely than White women to have short sleep duration. Sleep problems are prevalent among women with noncancerous gynecologic conditions, and are associated with depression and high pelvic problem impact. Providers should be proactive in inquiring about and offering solutions for sleep difficulties experienced by their patients.


Current Age, Age at First Sex, Age at First Homelessness, and HIV Risk Perceptions Predict Sexual Risk Behaviors among Sexually Active Homeless Adults.
While HIV disproportionately impacts homeless individuals, little is known about the prevalence of HIV risk behaviors in the southwest and how age factors and HIV risk perceptions influence sexual risk behaviors. We conducted a secondary data analysis (n = 460) on sexually active homeless adults from a cross-sectional study of participants (n = 610) recruited from homeless service locations, such as shelters and drop-in centers, in an understudied region of the southwest. Covariate-adjusted logistic regressions were used to assess the impact of age at homelessness onset, current age, age at first sex, and HIV risk perceptions on having condomless sex, new sexual partner(s), and multiple sexual partners (≥4 sexual partners) in the past 12 months. Individuals who first experienced homelessness by age 24 were significantly more likely to report condomless sex and multiple sexual partners in the past year than those who had a later onset of their first episode of homelessness. Individuals who were currently 24 years or younger were more likely to have had condomless sex, new sexual partners, and multiple sexual partners in the past 12 months than those who were 25 years or older. Those who had low perceived HIV risk had lower odds of all three sexual risk behaviors. Social service and healthcare providers should consider a younger age at homelessness onset when targeting HIV prevention services to youth experiencing homelessness.


Pathogenicity and seasonal variation of Aeromonas hydrophila isolated from seafood and ready-to-eat sushi in South Korea.
Aeromonas hydrophila is an emerging foodborne pathogen capable of causing human gastroenteritis, and the main reservoir is the aquatic environment. In this study, the prevalence and virulence of A. hydrophila in seafoods and ready-to-eat (RTE) sushi distributed in various conditions (refrigerated, dried, or frozen) or seasons was investigated. Strains were isolated from seafood (refrigerated or frozen oysters, sashimi, and processed fish; n = 333) and RTE sushi (n = 88) samples collected in South Korea and then genetically analyzed for gastroenteritis-related virulence genes (aer, ast, and alt). Raw oysters showed the highest prevalence of A. hydrophila (57.1%; 47/91) among all seafoods. Among the sashimi samples, flatfish sashimi (54.8%; 34/62) and salmon sushi (51.4%; 18/35) were the most prevalent. A. hydrophila was not detected in the oysters or anchovies distributed as either frozen or dried products. Seasonal investigations of sashimi and sushi showed that the summer prevalence of A. hydrophila with putative virulence genes was significantly lower in sashimi but highest in sushi. These results indicated that sushi could have been contaminated from several sources during the manufacturing or distribution processes. Significant correlations among the prevalence of putative virulence genes were confirmed, although no combination of genes presented a Phi correlation coefficient above 0.5 (0.26-0.43). To our knowledge, this is the first study to investigate the prevalence of A. hydrophila in various types of retail seafoods and RTE sushi in the East Asia region and then relate the prevalence to the distribution conditions of the samples. This study provides background information on the level of potential risk posed by A. hydrophila in retail seafoods and RTE sushi.


Rapid enrichment and analysis of yeast phosphoproteins using affinity chromatography, 2D-PAGE and peptide mass fingerprinting.
A combination of affinity purification, 2D-PAGE and peptide mass fingerprinting was employed to study the phosphoprotein complement of Saccharomyces cerevisiae. Protein extracts were first passed through a phosphoprotein affinity column, and the phosphoprotein-enriched eluate fractions were then separated on 2D gels and visualized by staining with SYPRO Ruby. Proteins were excised from the gels and identified by peptide mass fingerprinting; 11/13 protein spots identified from a gel of the phosphoprotein-enriched fraction had prior published evidence indicating that they were phosphoproteins. Additional experiments using a specific stain for phosphoproteins, prior incubation of the protein extract with alkaline phosphatase and blotting with monoclonal antibodies to phosphothreonine, phosphoserine and phosphotyrosine demonstrated that the phosphoprotein affinity column was an effective method for enriching phosphoproteins. Further validating the method, growth of yeast in the presence of sorbic acid resulted in altered phosphorylation of 17 proteins, 13 of which had prior published evidence that they were phosphoproteins or had ATP binding activity.


[The clinical study of the first febrile convulsion in children with brain-damage].
Forty-nine patients with cerebral palsy, mental retardation, or other congenital neurological disorders who had experienced febrile convulsions and had no previous nonfebrile seizures were presented. They were followed for 1.6 years to 15 years (mean: 6.8 years) after the initial febrile convulsion. The incidence of subsequent epilepsy (two or more afebrile seizures) was 39%, and 80% of them developed epilepsy within 2 years after the first febrile convulsion. The paroxysmal discharges on EEG recorded prior to or after the first febrile convulsion did not predict the occurrence of later epilepsy. Also under 3 years of age, EEG findings led to the same result. There was no definite evidence that administration of anticonvulsive drugs prevented later epilepsy. Pre-existing neurological abnormality was identified as a risk factor for epilepsy, and was an indication of persistent medication. There is no clear prophylactic procedure against long-lasting attacks. Accordingly, medical therapy can be started when epilepsy has developed. Patients with very severe brain damage who could not move except lying comprised only 6% of all cases, and 69% of the epilepsy patients were well controlled. They showed a good prognosis as compared with children with brain-damage in general with epilepsy.


Combined Detection of Plasma ZIC1, HOXD10 and RUNX3 Methylation is a Promising Strategy for Early Detection of Gastric Cancer and Precancerous Lesions.
We try to explore the value of aberrant DNA methylation of several cancer-related genes in plasma as non-invasive biomarkers for gastric cancer (GC) and precancerous lesions. By using methylation-specific polymerase chain reaction assay we determined the methylation status of three selected genes ZIC1, HOXD10 and RUNX3 in blood samples from patients with GC and precancerous lesions. We discovered that the methylation rate of ZIC1, HOXD10 and RUNX3 increased significantly in the progression of gastric carcinogenesis. Methylation of ZIC1 was associated with positive serum CA19-9, while that of HOXD10 was related to H. pylori status, serum CA19-9 and CEA levels and tumor invasion depth. The Odds ratios (ORs) of ZIC1, HOXD10 and RUNX3 methylation for predicting GC were 4.285 (95%CI: 2.435-7.542), 3.133 (95%CI: 1.700-5.775) and 2.674 (95%CI: 1.441-4.960), while for predicting "gastric cancer and intraepithelial neoplasia" (GnI), the ORs were 12.011 (95%CI: 0.050-28.564), 9.174 (95%CI: 3.220-26.135) and 12.794 (95%CI: 4.115-39.778), respectively. In terms of combined detection of these three genes, the sensitivity was 91.6% for GC and 89.8% for GnI, with the highest Youden index in both GC and GnI determination. Conclusively, combined detection of ZIC1, HOXD10 and RUNX3 promoter hypermethylation might be a promising strategy for early detection of GC and precancerous lesions.


Epidemiology, injury characteristics and clinical outcomes of bicycle and motorcycle accidents in the under 20 population: South Korea.
Bicycles and motorcycles are a main means of transportation and leisure for individuals aged under 20 years in South Korea. We aimed to identify the epidemiology of injuries and describe and compare patterns of injury and clinical outcomes of two-wheel vehicle-related accidents in these individuals. We analysed data obtained from the National Emergency Department Information System for 401 emergency departments (EDs) from January 2016 to December 2018. We included patients aged < 20 years who experienced injuries while driving or a passenger on two-wheeled vehicles. We analysed patients with a bicycle-related injury and those with a motorcycle-related injury, and then compared two groups and performed a regression analysis for factors predicting severe trauma. This study enrolled 54,342 two-wheel vehicle injury patients (37,410 bicycle and 16,932 motorcycle-related), of which, 86.8% (bicycle) and 94.9% (motorcycle) were males. External injuries were the most common. ED mortality was 9 (0.0%) for bicycles and 53 (0.3%) for motorcycles. Overall, 3,346 (8.9%) patients were hospitalised with bicycle injuries and 4,096 (24.2%) with motorcycle injuries. Among admitted patients with bicycle-related injuries, 48.7% had upper extremity injuries and among those admitted patients with motorcycle-related injuries, 76.0% had lower extremity injuries. Among hospitalised patients, the mean injury severity score (ISS) was 12.0 ± 12.6 in bicycle-related injury and 17.6 ± 15.4 in motorcycle-related injury. The number of patients with ISS ≥ 16 was 27.6% for bicycle related injuries and 45.2% for motorcycle-related injuries. The mean length of hospital stay was 191.5.8 ± 224.2 h for bicycle injury, and 359.6 ± 416.7 h for motorcycles. Hospital mortality cases were 0.2% with bicycle injury and 1.2% with motorcycle injury. Motorcycle-related injuries had more severe injury (ISS ≥ 16), with an adjusted odds ratio of 2.825 (95% confidence interval 2.610-3.059) compared to bicycle-related injuries. In the population aged under 20 years, two-wheel vehicle-related occurred predominantly in males. When using two-wheeled vehicles, motorcycle injuries were higher in patients aged over 14 years and were associated with higher ISS (≥ 16). Political efforts should be made to educate under 20 years of age for safe driving and to wear protective gear, including helmets to prevent severe injury.


Molecular characterization of two stamen-specific genes, tap1 and fil1, that are expressed in the wild type, but not in the deficiens mutant of Antirrhinum majus.
Deficiens, a homeotic gene involved in the genetic control of flower development, codes for a putative transcription factor. Upon mutation of the gene, petals are transformed to sepals and stamens to carpels, indicating that deficiens is essential for the activation of genes required for petal and stamen formation. In a search for putative target genes of deficiens, several stamen- and petal-specific genes were cloned that are expressed in wild type but not in the deficiensglobifera mutant. In this report the molecular characterization of two of these genes, tap1 and fil1, is presented. They are transiently expressed during flower development. In situ hybridization data demonstrate that tap1 is expressed in the tapetum of the anthers and fil1 in the filament of the stamen and at the bases of the petals. Both genes encode small proteins with N-terminal hydrophobic domains suggesting that they are secreted. We discuss possible functions of the gene products and their relationship to the deficiens gene.


A sensitive and high throughput method for the analysis of d-psicose by capillary electrophoresis.
d-Psicose/allulose is a rare sugar and it has high potential benefits for pharmaceutical and food industry. The existed analytical methods have its own limitations to quantify fructose and d-psicose mixtures. Hence there is a need for the development of an effective, efficient and sensitive analytical method for quantification of d-psicose in presence of other sugars. Quantification of sugars by capillary electrophoresis (CE) have been previously reported. However, the list does not include d-psicose. In this study, d-psicose is successfully quantified for the first time in the presence of d-fructose and glucose with a good resolution. Standard curves for all the sugars are established in a concentration range of 0.1 mM (0.0018% w/v) to 3.0 mM (0.0540% w/v) with a coefficient of determination of >0.99. The scope of this method can be extended to quantify d-psicose and their processed impurities in food products with minor modifications in sample preparation.


Bilingualism, executive control, and age at diagnosis among people with early-stage Alzheimer's disease in Wales.
The observation of a bilingual advantage in executive control tasks involving inhibition and management of response conflict suggests that being bilingual might contribute to increased cognitive reserve. In support of this, recent evidence indicates that bilinguals develop Alzheimer's disease (AD) later than monolinguals, and may retain an advantage in performance on executive control tasks. We compared age at the time of receiving an AD diagnosis in bilingual Welsh/English speakers (n = 37) and monolingual English speakers (n = 49), and assessed the performance of bilinguals (n = 24) and monolinguals (n = 49) on a range of executive control tasks. There was a non-significant difference in age at the time of diagnosis, with bilinguals being on average 3 years older than monolinguals, but bilinguals were also significantly more cognitively impaired at the time of diagnosis. There were no significant differences between monolinguals and bilinguals in performance on executive function tests, but bilinguals appeared to show relative strengths in the domain of inhibition and response conflict. Bilingual Welsh/English speakers with AD do not show a clear advantage in executive function over monolingual English speakers, but may retain some benefits in inhibition and management of response conflict. There may be a delay in onset of AD in Welsh/English bilinguals, but if so, it is smaller than that found in some other clinical populations. In this Welsh sample, bilinguals with AD came to the attention of services later than monolinguals, and reasons for this pattern could be explored further.


Hypofractionated stereotactic radiotherapy after transarterial chemoembolisation failure in an unresectable hepatocellular carcinoma: a case presentation.
Introduction. Transarterial chemoembolization is the first-line treatment in unresectable hepatocellular carcinoma. There is no standard treatment after transarterial chemoembolization failure. We report the case of a patient with advanced hepatocellular carcinoma who showed a complete response and a long cancer control with hypofractionated stereotactic radiotherapy after transarterial chemoembolization failure. Case Presentation. A 70-year-old Caucasian woman was treated with transarterial chemoembolization for advanced hepatocellular, but no cancer control was obtained. A hypofractionated stereotactic radiotherapy was planned delivering 40 Gy in 5 fractions. A dramatic reduction in alpha-fetoprotein was observed. Contrast-enhanced ultrasonography at 1 and 2 months showed large necrotic areas. Computerised tomography scan showed a 90% objective tumour response, then a complete remission at 3 and 6 months after treatment, respectively. Status of patient remained unchanged for 2 years. Conclusions. Hypofractionated stereotactic radiotherapy can improve survival and prognosis of unresectable hepatocellular carcinoma patient.


The HIV-1 Tat protein has a versatile role in activating viral transcription.
It is generally acknowledged that the Tat protein has a pivotal role in HIV-1 replication because it stimulates transcription from the viral long terminal repeat (LTR) promoter by binding to the TAR hairpin in the nascent RNA transcript. However, a multitude of additional Tat functions have been suggested. The importance of these functions is difficult to assess in replication studies with Tat-mutated HIV-1 variants because of the dominant negative effect on viral gene expression. We therefore used an HIV-1 construct that does not depend on the Tat-TAR interaction for transcription to reevaluate whether or not Tat has a second essential function in HIV-1 replication. This HIV-rtTA variant uses the incorporated Tet-On gene expression system for activation of transcription and replicates efficiently upon complete TAR deletion. Here we demonstrated that Tat inactivation does nevertheless severely inhibit replication. Upon long-term culturing, the Tat-minus HIV-rtTA variant acquired mutations in the U3 region that improved promoter activity and reestablished replication. We showed that in the absence of a functional TAR, Tat remains important for viral transcription via Sp1 sequence elements in the U3 promoter region. Substitution of these U3 sequences with nonrelated promoter elements created a virus that replicates efficiently without Tat in SupT1 T cells. These results indicate that Tat has a versatile role in transcription via TAR and U3 elements. The results also imply that Tat has no other essential function in viral replication in cultured T cells.


Dexmedetomidine protects against renal ischemia and reperfusion injury by inhibiting the P38-MAPK/TXNIP signaling activation in streptozotocin induced diabetic rats.
To determine whether dexmedetomidine (DEX) could attenuate acute kidney injury (AKI) induced by ischemia/reperfusion (I/R) in streptozotocin (STZ)-induced diabetic rats. Four groups each containing six rats were created (sham control(S), diabetes-sham (DS), diabetes I/R (DI/R), and diabetes-I/R-dexmedetomidine (DI/R-DEX). In diabetes groups, single-dose (65 mg/kg) STZ was administered intraperitoneally (i.p.). In Group DI/R, ischemia reperfusion was produced via 25 min of bilateral renal pedicle clamping followed by 48 h of reperfusion. In Group DI/R-DEX, 50 μg/kg dexmedetomidine was administered intraperitoneally 30 minutes before ischemia. Renal function, histology, apoptosis, the levels of TNF-α, IL-1β, and oxidative stress in diabetic kidney were determined. Moreover, expression of P38 mitogen-activated protein kinase (P38-MAPK), phosphorylated-P38-MAPK(p-P38-MAPK) and thioredoxin-interacting protein (TXNIP) were assessed. The degree of renal I/R injury was significantly increased in DI/R group compared with S group and DS group. The levels of TNF-α, IL-1β, oxidative stress and apoptosis were found significantly higher in DI/R Group when compared with S Group and DS Group. The protein expression of p-P38-MAPK and TXNIP were significantly increased after I/R. All these changes were reversed by DEX treatment. The renoprotective effects of DEX-pretreatment which attenuates I/R-induced AKI were partly through inhibition of P38-MAPK activation and expression of TXINP in diabetic kidney.


Differential impact of simple childhood obesity on the components of the growth hormone-insulin-like growth factor (IGF)-IGF binding proteins axis.
Simple childhood obesity is characterized by normal or even accelerated growth in spite of reduced growth hormone (GH) secretion. There are conflicting reports on the effects of obesity upon components of the GH-insulin-like growth factor-I (IGF-I)-IGF binding proteins (IGFBPs) system. In the present study we aimed to determine GH, IGF-I, IGFBP-3 and IGFBP-2 as well as some of the less explored components of this axis (IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments, and total acid labile subunit [ALS]) in 22 obese and 17 age-matched control children. We also evaluated not only total GH binding protein (GHBP) serum levels but also GHBP bound to GH (complexed) in both groups. Obese and control groups strongly differed in BMI (obese: 4.7 +/- 0.36 vs control: 0.37 +/- 0.25 SDS, p <0.0001). In the obese group, we found lower GH serum levels, but normal serum levels of GH-GHBP complex, IGF-I, IGFBP-3, IGF-I/IGFBP-3 molar ratio, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Obese children presented higher total circulating GHBP (6.0 +/- 0.44 vs 2.9 +/- 0.29 nmol/l, p <0.001) and insulin levels (10.5 +/- 1.5 vs 5.1 +/- 0.8 mU/l, p <0.001), while IGFBP-2 (4.6 +/- 0.5 vs 6.6 +/- 0.7%, p <0.05) and the ratio IGFBP-2/IGF-I (0.032 +/- 0.019 vs 0.095 +/- 0.01, p = 0.013) were lower than in controls. BMI and insulin were directly, and IGFBP-2 serum levels inversely, correlated to total GHBP serum levels when multiple regression analysis was performed (r = 0.74, p <0.001). By stepwise regression analysis, insulin (r = -0.37, p <0.05) and BMI (r = -0.52, p <0.01) inversely determined IGFBP-2. In summary, obese children present normal growth in spite of reduced GH secretion, probably because the combination of increased total GHBP and normal GH-GHBP complex serum levels (suggesting increased GH receptor [GHR] number and a normal serum GH reservoir, respectively) allow for the achievement of normal levels of IGF-I, IGFBP-3, IGFBP-3 proteolytic activity, IGFBP-3 plasma fragments and total ALS. Reduced IGFBP-2 serum levels and a lower ratio of IGFBP-2/IGF-I in obese children may suggest an increase of tissue IGF-I bioavailability, thus promoting its action. Normal IGF-I and GH availability may be contributing to maintain normal growth in obese children.


Surgical management of cavernous angiomas in children.
Cavernous angiomas are vascular malformations affecting any part of the central nervous system (CNS). The management of asymptomatic cavernous angiomas is still debated due to their poorly understood natural history, although more data are now available regarding results of surgical treatment in symptomatic cases. The authors report their surgical experience with 18 pediatric patients operated on for symptomatic CNS cavernous angiomas. The children ranged in age from 10 months to 17 years, without a relevant sex difference. Cavernous angiomas were intracranial in 17 cases: 15 being in the supratentorial compartments and two in the cerebellum. Clinical manifestations were as follows: seizures in 11 cases, focal neurologic deficits in five, and headache in one. The 18th case was observed in a girl showing paraparesis in the spinal subdural-extramedullary space at T8-T9 level. Excision of four deep cerebral lesions was performed after stereotactic localization through non-eloquent cortex. Pathologic confirmation of cavernous angiomas was obtained in all patients. Mortality from surgical procedures was absent in this series. The follow-up period ranged from 1 to 16 years. All 11 epileptic patients obtained seizure control; improvement or stabilization of neurologic symptoms was observed in the remaining seven patients.


[Evaluation of the effect of premenopausal oophorectomy on bone mineral content].
The effects of premenopausal oophorectomy on bone mineral content (BMC) and serum parameters of bone metabolism, ie E2, PTH, Ca, P, ALP, BGP, 1-25(OH)2D3 were studied. The BMC of the spongiosum of L-3 vertebral body was calculated by means of computed tomography which was utilized in conjunction with a calibrated phantom containing a set of reference densities (CaCO3). The BMC tended to decrease markedly in the late 40s (r = -0.669, p less than 0.01) and a 38% decrease was found among the postmenopausal group (age 50-60) in comparison with the premenopausal group (age 40-49) (206.9 +/- 38.0 vs 128.5 +/- 32.7 mg/cm3, p less than 0.005). In cases of premenopausal bilateral oophorectomy (mean age 42.5) the BMC was found to decrease significantly about 2 years after the operation (150.0 +/- 25.2 mg/cm3, p less than 0.005), while no significant difference was found between the controls (mean age 43.5) and unilateral oophorectomized cases (mean age 40.3). Findings that indicated a decrease in E2, a significant increase in BGP and ALP, and a tendency for PTH to decrease were noted among bilateral oophorectomized cases and this may indicate accelerated osteogenesis. It was suggested that premenopausal bilateral oophorectomized cases are in danger of developing severe osteoporosis and are candidates for rigorous preventive treatment.


Mechanical Properties of Aluminum Alloys under Low-Cycle Fatigue Loading.
In this paper, the mechanical properties of 36 aluminum alloy specimens subjected to repeated tensile loading were tested. The failure characteristics, stress-strain hysteresis curves and its corresponding skeleton curves, stress cycle characteristics, and hysteretic energy of specimens were analyzed in detail. Furthermore, the finite element model of aluminum alloy specimens under low-cycle fatigue loading was established and compared with the experimental results. The effects of specimen parallel length, parallel diameter, and repeated loading patterns on the mechanical properties of aluminum alloys were discussed. The results show that when the specimen is monotonously stretched to fracture, the failure result from shearing break. When the specimen is repeatedly stretched to failure, the fracture of the specimen is a result of the combined action of tensile stress and plastic fatigue damage. The AA6061, AA7075, and AA6063 aluminum alloys all show cyclic softening characteristics under repeated loading. When the initial stress amplitude of repeated loading is greater than 2.5%, the repeated tensile loading has a detrimental effect on the deformability of the aluminum alloy. Finally, based on experiment research as well as the results of the numerical analysis, the calculation method for the tensile strength of aluminum alloys under low-cycle fatigue loading was proposed.


Cyclic peptide-based nanostructures as efficient siRNA carriers.
RNA interference shows a great strategy for biological studies; however, delivering of small interfering RNA (siRNA) remains challenging. Although several delivery vehicles, including cell-penetrating peptides, have been developed, their implementation is often restricted because of their endosomal entrapment. Herein, we report the formation of self-assembled nanostructures from rationally designed cyclic peptides and explore them for efficient delivery of functional biomacromolecules such as siRNA into mammalian cells. The newly obtained soft materials make stable complexes with siRNAs, thereby increasing their stability and deliver fluorescent labelled siRNA inside the cells as evident from confocal microscopy analysis. Flow cytometry analysis reveals that significant uptake of FAM-siRNA occurs in the presence of peptide nanostructures compared with siRNA alone. Peptide nanostructure-mediated delivery of very low concentration of siRNA causes significant knockdown of the target gene as observed at protein level by Western blot analysis, which is comparable to lipofectamine, commercially available transfection agent.


Dental management of a patient with oculo-facio-cardio-dental syndrome.
Oculo-facio-cardio-dental (OFCD) syndrome is an X-linked dominant syndrome characterized by congenital cataract, microphtalmia, secondary glaucoma, long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, atrial septal defect (ASD), ventricular septal defect (VSD), radiculomegaly, delayed eruption, oligodontia, and persistence of primary teeth. The aim of this report is to indicate the importance of early diagnosis and management of oculo-facio-cardio-dental syndrome.


High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence.
Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post-administration interval. In Experiment 2, adolescent rats were assessed for ethanol-induced locomotor activation on postnatal Day 28. These animals were then evaluated for ethanol-mediated conditioned taste aversion and underwent a 16-day-long ethanol intake protocol. Ethanol-mediated aversive effects were unrelated to ethanol locomotor stimulation or subsequent ethanol consumption patterns. Ethanol intake during late adolescence was greatest in animals initiated to ethanol earliest at postnatal Day 28. Females that were more sensitive to ethanol's locomotor-activating effects showed a transient increase in ethanol self-administration. Blood ethanol concentrations during initiation were not related to ethanol-induced locomotor activation. Adolescent rats appeared sensitive to the locomotor-stimulatory effects of ethanol. Even brief ethanol exposure during adolescence may promote later ethanol intake.


Cocaine- and amphetamine-regulated transcript peptide (CART) is present in peptidergic C primary afferents and axons of excitatory interneurons with a possible role in nociception in the superficial laminae of the rat spinal cord.
Cocaine- and amphetamine-regulated transcript peptides (CART) have been implicated in the regulation of several physiological functions, including pain transmission. A dense plexus of CART-immunoreactive fibres has been described in the superficial laminae of the spinal cord, which are key areas in sensory information and pain processing. In this study, we used antibody against CART peptide, together with markers for various types of primary afferents, interneurons and descending systems to determine the origin of the CART-immunoreactive axons in the superficial laminae of the rat spinal cord. Calcitonin gene-related peptide (CGRP), a marker for peptidergic primary afferents in the dorsal horn, was present in 72.6% and 34.8% of CART-immunoreactive axons in lamina I and II, respectively. The majority of these fibres also contained substance P (SP), while a few were somatostatin (SOM)-positive. The other subpopulation of CART-immunoreactive boutons in lamina I and II also expressed SP and/or SOM without CGRP, but contained vesicular glutamate transporter 2, which is present mainly in excitatory interneuronal terminals. Our data demonstrate that the majority of CART-immunoreactive axons in the spinal dorsal horn originate from peptidergic nociceptive primary afferents, while the rest arise from excitatory interneurons that contain SP or SOM. This strongly suggests that CART peptide can affect glutamatergic neurotransmission as well as the release and effects of SP and SOM in nociception and other sensory processes.


Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB.
PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 A resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.


An infected porous polyethylene orbital implant.
A 75-year-old man underwent enucleation with placement of a porous polyethylene orbital implant (Medpor, Porex Technologies, Fairburn, GA, U.S.A.). Over the next 5 years, he was seen on numerous occasions with socket discharge that was unresponsive to a variety of eyedrops. Exposure and re-exposure of the implant occurred, and the implant was removed. Histopathologic assessment was consistent with an infectious process within the implant. Postoperatively, the patient's symptoms and signs resolved. Porous orbital implant infection is rare. The diagnosis may be delayed as the initial symptoms and signs (discharge, conjunctival inflammation) may easily be attributed to prosthesis wear. With time, and persistence of the symptoms despite numerous treatments, infection should be suspected.


Geldanamycin leads to superoxide formation by enzymatic and non-enzymatic redox cycling. Implications for studies of Hsp90 and endothelial cell nitric-oxide synthase.
The ansamycin antibiotic geldanamycin has frequently been used as an inhibitor of heat shock protein 90 (Hsp90), and this agent has been widely employed as a probe to examine the interactions of Hsp90 with endothelial nitric-oxide synthase. Geldanamycin contains a quinone group, which may participate in redox cycling. When geldanamycin was exposed to the flavin-containing enzyme cytochrome P-450 reductase, both semiquinone and superoxide (O(2)(*)(-)) radicals were detected using electron spin resonance. The treatment of endothelial cells with geldanamycin resulted in a dramatic increase in O(2)(*)(-) generation, which was independent of endothelial nitric-oxide synthase, because it was not inhibited by N-nitro-l-arginine methyl ester and also occurred in vascular smooth muscle cells. Diphenylene iodinium inhibited this increase in O(2)(*)(-) by 50%, suggesting that flavin-containing enzymes are involved in geldanamycin-induced O(2)(*)(-) generation. In the absence of cells, geldanamycin directly oxidized ascorbate, consumed oxygen, and produced O(2)(*)(-). Geldanamycin decreased the bioavailable nitric oxide generated by 3,4-dihydrodiazete 1,2-dioxide in smooth muscle cells by 50%, whereas pretreatment with superoxide dismutase inhibited the effect of geldanamycin. These findings demonstrate that geldanamycin generates O(2)(*)(-), which scavenges nitric oxide, leading to loss of its bioavailability. This effect is independent of the inhibition of Hsp90 and indicates that geldanamycin cannot be used as a specific inhibitor of Hsp90. In light of these findings, the studies using geldanamycin as an inhibitor of Hsp90 should be interpreted with caution.


An existential approach to risk perception.
Existential, or existential-phenomenological philosophical approaches to the social psychology of risk perception provide a novel framework for understanding issues that are common to all humanity, such as fear of death, freedom and responsibility, isolation and meaninglessness, as these anxieties are a function of existing, or being-in-the-world. These fundamental anxieties can be related theoretically to the ways people perceive risks within social and cultural milieus, and can also be used practically within case studies, as demonstrated in the three examples presented, which examine perceptions of climate change, food-related risks, and environmental awareness via a mixture of quantitative and qualitative techniques. The discussion focuses on the possible insights that can be gained from taking an existential perspective on risk perception, and relates notions of contemporary technologically-oriented societies to the existential challenges faced by individuals and societies in the contemporary world.


Synthesis of disaccharides related to the O-specific polysaccharide of Salmonella typhimurium.
Methyl 2-O-benzyl-4,6,-O-benzylidene-alpha-D-mannopyranoside (13) has been glycosylated with 3,6-dideoxy-2,4-di-O-p-nitrobenzoyl-alpha-D-xylo-hexopyranosyl bromide (4) and its enantiomer (5) using mercury cyanide as catalyst and toluene and nitromethane as solvent. The anomeric ratio has been determined by 1H NMR spectroscopy and is reversed going from the D to the L compound. Glycosylation of 13 with 2-O-benzyl-3,6-dideoxy-4-O-p-nitrobenzoyl-alph-D-xylo-hexopyranosyl bromide (9) under similar reaction conditions gives exclusively the alpha-linked disaccharide while glycosylation using 2,4-di-O-benzyl-3,6-dideoxy-alpha-D-xylo-hexopyranosyl chloride (12) gives a 1:3 mixture of beta- and alpha-linked disacchrides. Glycosylation of 13 with 12, catalyzed by tetrabutylammonium bromide at elevated temperature, yields exclusively the alpha-linked disaccharide. The conformation of two of the deprotected disaccharides has been determined using hard sphere calculations and high field NMR data.


Identification of Erectile Dysfunction Drugs in Dietary Supplements by Liquid Chromatography Ion Trap Mass Spectrometry.
With the rise in consumption of dietary supplements for various ailments such as erectile dysfunction (ED), there is concern that these supplements may contain illegally added phosphodiesterase type 5 (PDE-5) inhibitor and its analogs. HPLC or LC is a general separation method, and MS is a detection technique, together LC/MS/MS technology provides the mass spectral confirmation in identifying sildenafil, vardenafil, tadalafil and their analogs. In our present study, a sample extraction technique with 1:1 acetonitrile: water solvents and sonication was used for screening, then identification was performed using an LC coupled with Velos Pro linear ion trap mass spectrometry. This was a simple and reliable method for a variety of matrices of dietary supplements and pharmaceutical formulations in tablet, capsule or liquid form. The run time is only 6.5 min, allowing for a quick screening and identification of all of analytes of ED drugs using full scan and data-dependent scan MS/MS, except for tadalafil and aminotadalafil (MS/MS/MS). To conclude this study, Sildenafil, tadalafil, vardenafil, and other 16 analogs in dietary supplements could be quickly screened and identified by HPLC coupled with ion trap MS using data dependent scanning function. The main method using the short column is very rapid, and saves a lot of running time and solvents, and the identification is further confirmed by MS/MS information. The current study develops and validates a quick and reliable method to screen for ED drugs.


Personality disorders, depression, and coping styles in Argentinean bulimic patients.
This study investigates the coping styles of bulimic patients with personality disorders (PDs) and the effects of the level of depression on the relations between PDs and coping. The sample consisted of 75 Argentinean bulimic outpatients engaged in treatment. Patients completed the SCID II (Structural Interview for DSM IV-Personality Disorders), COPE (Coping Inventory), and the SCL-90-R (Symptom Checklist-90-Revised). No differences in the coping styles of bulimic patients with or without a PD were found. However, when three specific PDs were considered-Avoidant, Obsessive-Compulsive, or Borderline PDs-clear differences in the coping styles of the bulimics were found. However, the differences disappeared when depression was controlled. Regarding the severity of the three specific PDs, coping styles were only found to be associated with the Avoidant PD. Depression showed to affect the relations between coping styles and two specific PDs-Avoidant and Borderline PDs-in bulimic patients.


A new approach for the characterization of reverse micellar systems by dynamic light scattering.
This paper reports the use of dynamic light scattering (DLS) to study reverse micelles formed by the water/Igepal CO-520/cyclohexane system over a large range of global compositions. A novel approach for data analysis is presented, based on the realization that micelles of a given size must be in equilibrium with free surfactant of a fixed concentration. Compilation of the DLS data into sets of fixed micelle size but differing global compositions therefore allows for the determination of parameters such as free surfactant concentration, micellar molar composition, surfactant interfacial area, and aggregation numbers. Importantly, this method gives access to the variation of each of these parameters with micelle size, as is essential for the characterization of reverse micelles formed by nonionic surfactants. This approach constitutes a significant complement to other available characterization methods. The analysis also provides insight into the primary factors controlling the equilibrium distribution of surfactant within the system and the relative stability of the micelles.


Can N95 Respirators Be Reused after Disinfection? How Many Times?
The coronavirus disease 2019 (COVID-19) pandemic has led to a major shortage of N95 respirators, which are essential for protecting healthcare professionals and the general public who may come into contact with the virus. Thus, it is essential to determine how we can reuse respirators and other personal protective equipment in these urgent times. We investigated multiple commonly used disinfection schemes on media with particle filtration efficiency of 95%. Heating was recently found to inactivate the virus in solution within 5 min at 70 °C and is among the most scalable, user-friendly methods for viral disinfection. We found that heat (≤85 °C) under various humidities (≤100% relative humidity, RH) was the most promising, nondestructive method for the preservation of filtration properties in meltblown fabrics as well as N95-grade respirators. At 85 °C, 30% RH, we were able to perform 50 cycles of heat treatment without significant changes in the filtration efficiency. At low humidity or dry conditions, temperatures up to 100 °C were not found to alter the filtration efficiency significantly within 20 cycles of treatment. Ultraviolet (UV) irradiation was a secondary choice, which was able to withstand 10 cycles of treatment and showed small degradation by 20 cycles. However, UV can potentially impact the material strength and subsequent sealing of respirators. Finally, treatments involving liquids and vapors require caution, as steam, alcohol, and household bleach all may lead to degradation of the filtration efficiency, leaving the user vulnerable to the viral aerosols.


A children's Spanish word discrimination test for non-Spanish-speaking clinicians.
A picture-pointing speech discrimination test which can be efficiently administered by English-speaking clinicians to Spanish-speaking children was developed. The test consists of four lists of 25 bisyllabic words. Two syllable words were chosen as stimuli instead of the traditional monosyllabic words because of the limited number of concrete monosyllabic words in Spanish. These words were recorded in Spanish on the first channel of an audio tape and in English on the second channel. The purpose of this dual recording was to present the Spanish stimuli to the subjects at the same time the clinicians monitored the appropriateness of responses in English.


Kidney grafts from donors ≤ 5 yr of age: single kidney transplantation for pediatric recipients or en bloc transplantation for adults?
Kidneys from donors ≤5 yr of age represent a controversial issue. The purpose of this study was to compare the transplant outcomes as single and single/en bloc grafts into pediatric and adult KT recipients, respectively. All recipients of kidneys from donors ≤5 yr old transplanted at our institution from 3/2003 to 12/2010 were evaluated, and corresponding data were analyzed. There were 11 pediatric and 14 adult recipients. Median donor age and body weight were 38 months and 14 kg, respectively. PNF, n = 2 and DGF, n = 1 were observed only among adult recipients. Five-yr graft survival was 100% for children and 86% for adults. There were no significant differences in graft and patient survival, PNF, DGF, acute rejection, or postoperative complications among children/single (n = 10), adults/en bloc (n = 10), and adults/single (n = 4) KT. Major complications were documented in six adult recipients and one pediatric recipient after en bloc KT. Pediatric recipients showed significantly higher GFR during the first post-transplant year. Kidneys from donors ≤5 yr of age have at least as good outcomes as when transplanted as single allografts into children. Although the study-volume is small, it seems that children benefit from a pediatric-oriented allocation policy.