Clinical Features and Voxel-Based-Symptom-Lesion Mapping of Silent Aspiration in Acute Infratentorial Stroke.
Post-stroke dysphagia (PSD) is a severe and common complication after ischemic stroke. The role of silent aspiration as an important contributing factor in the development of a dysphagia-associated complications, in particular aspiration-associated pneumonia has been insufficiently understood. The aim of this study was to investigate the characteristics and risk factors of silent aspiration in patients with acute infratentorial stroke by FEES and to identify culprit lesions in stroke patient with a high risk of silent aspiration via voxel-based-symptom-lesion mapping (VBS/ML). This study is a retrospective observational study based on a prospectively collected FEES and stroke database. Consecutive patient cases with acute ischemic infratentorial stroke and FEES examination between 2017 and 2022 were identified. Group allocation was performed based on PAS scores. Imaging analysis was performed by manual assignment and by VBS/ML. Group comparisons were performed to assess silent aspiration characteristics. Binary logistic regression analysis was performed to determine if baseline clinical, demographic, and imaging parameters were helpful in predicting silent aspiration in patients. In this study 84 patient cases with acute infratentorial stroke who underwent FEES examination were included. Patients were moderately affected at admission (mean NIH-SS score at admission 5.7 SD ± 4.7). Most lesions were found pontine. Overall 40.5% of patients suffered from silent aspiration, most frequently in case of bilateral lesions. Patients with silent aspiration had higher NIH-SS scores at admission (p < 0.05), had a more severe swallowing disorder (p < 0.05) and were 4.7 times more likely to develop post-stroke pneumonia. Patients who underwent FEES examination later than 72 h after symptom onset were significantly more likely to suffer from silent aspiration and to develop pneumonia compared to patients who underwent FEES examination within the first 72 h (p < 0.05). A binary logistic regression model identified NIH-SS at admission as a weak predictor of silent aspiration. Neither in manual assignment of the lesions to brain regions nor in voxel-wise statistic regression any specific region was useful in prediction of silent aspiration. Silent aspiration is common in patients with infratentorial stroke and contributes to the risk for pneumonia. Patients with silent aspiration are more severely affected by stroke, but cannot reliably be identified by NIH-SS at admission or lesion location. Patients suffering from acute infratentorial stroke should been screened and examined for PSD and silent aspiration.


Summary of current cooperative group clinical trials in thoracic malignancies. The Thoracic Intergroup.
Historically, thoracic surgeons have played a pivotal role in the success of clinical trials for early-stage thoracic malignancies. This is illustrated by the experience of the Veterans Administration Surgical Oncology Group and by the Lung Cancer Study Group. Since the dissolution of the Lung Cancer Study Group, the other cooperative groups have been unable to complete any large randomized trials because of a lack of surgical participation. A group of thoracic surgeons is now addressing this problem by unifying research efforts across the cooperative groups. The aim of this summary is to disseminate information about those efforts, and to encourage the involvement of North American thoracic surgeons in current clinical trials.


Identification and characterization of quantitative trait loci that control seed dormancy in Arabidopsis.
Seed dormancy is a trait that is under multigenic control and affected strongly by environmental factors. Thus, seed dormancy is a typical quantitative trait. Natural accessions of Arabidopsis thaliana exhibit a great deal of genetic variation for seed dormancy. This natural variation can be used to identify genes controlling this trait by means of quantitative trait loci (QTL) mapping. In this chapter, we describe how QTL mapping for seed dormancy in Arabidopsis thaliana can be performed and how QTL analyses can be used to eventually identify the causal gene. Methods and recourses available specifically for Arabidopsis are described or referred to.


Prenatal hypoxia is associated with long-term retinal dysfunction in rats.
Intra-uterine growth restriction (IUGR) has been associated with increased predisposition to age-related complications. We tested the hypothesis that rat offspring models of IUGR would exhibit exacerbated, age-related retinal dysfunction. Female Sprague-Dawley rats (maintained at 11.5% O2 from gestational day 15 to 21 to induce IUGR) and control offspring (maintained at 21% O2 throughout pregnancy) had retinal function assessed at 2 months (young) and 14 months of age (aged) with electroretinogram (ERG) recordings. Retinal anatomy was assessed by immunofluorescence. Deficits in rod-driven retina function were observed in aged IUGR offspring, as evidenced by reduced amplitudes of dark-adapted mixed a-wave V(max) (by 49.3%, P < 0.01), b-wave V(max) (by 42.1%, P < 0.001) and dark-adapted peak oscillatory potentials (by 42.3%, P < 0.01). In contrast to the rod-driven defects specific to aged IUGR offspring, light adapted ERG recordings revealed cone defects in young animals, that were stationary until old age. At 2 months, IUGR offspring had amplitude reductions for both b-wave (V(max) by 46%, P < 0.01) and peak oscillatory potential (V(max) by 38%, P < 0.05). Finally, defects in cone-driven responses were further confirmed by reduced maximal photopic flicker amplitudes at 2 (by 42%, P < 0.001) and 14 months (by 34%, P = 0.06) and critical flicker fusion frequencies at 14 months ( 42 ± 1 Hz, IUGR: 35 ± 2 Hz, P < 0.05). These functional changes were not paralleled by anatomical losses in IUGR offspring retinas. These data support that the developing retina is sensitive to stressors, and that pathways governing cone- and rod-driven function differ in their susceptibilities. In the case of prenatal hypoxia, cone- and rod-driven dysfunction manifest at young and old ages, respectively. We must, therefore, take into account the specific impact that fetal programming might exert on age-related retinal dystrophies when considering related diagnoses and therapeutic applications.


Level of Vascular Inflammation Is Higher in Acute Coronary Syndromes Compared with Chronic Coronary Disease.
Vascular inflammation has been recognized as one of the key factors in the pathogenesis of acute coronary syndromes (ACS). Pericoronary adipose tissue (PCAT) attenuation by computed tomography angiography has emerged as a marker specific for coronary artery inflammation. We examined the relationship between clinical presentation and coronary artery inflammation assessed by PCAT attenuation and coronary plaque characteristics. Patients with ACS or stable angina pectoris (SAP) who underwent preintervention coronary computed tomography angiography and optical coherence tomography were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries. PCAT attenuation and optical coherence tomography findings were compared between patients with ACS versus SAP. Among 471 patients (ACS: 198, SAP: 273), PCAT attenuation was higher in ACS patients than in SAP patients both at the culprit plaque level (-67.5±9.6 Hounsfield unit [HU] versus -71.5±11.0 HU, P<0.001) and at the culprit vessel level (-68.3±7.7 HU versus -71.1±7.9 HU, P<0.001). The mean PCAT attenuation of all 3 coronary arteries was also significantly higher in ACS patients than in SAP patients (-68.8±6.3 HU versus -70.5±7.1 HU, P=0.007). After adjusting patient characteristics, not only thin-cap fibroatheroma (OR: 3.41; 95% CI: 1.89-6.17) and macrophages (OR: 3.32; 95% CI: 1.76-6.26) but also PCAT attenuation around the culprit plaque (OR: 1.03; 95% CI: 1.00-1.05) was associated with the clinical presentation of ACS. PCAT attenuation at culprit plaque, culprit vessel, and pan-coronary levels was higher in ACS patients than in SAP patients. Vascular inflammation appears to play a crucial role in the development of ACS. URL: https://www. gov; Unique identifier: NCT04523194.


Gene expression and functional analysis of zebrafish larval fin fold regeneration.
Teleost fish have a remarkable ability to regenerate their body parts compared to many higher vertebrates including humans. To facilitate molecular and genetic approaches for regeneration, we previously established an assay using the fin fold of zebrafish larvae. Here, we performed transcriptional profiling and identified genes differentially controlled during regeneration. From up-regulated transcripts, we identified a number of genes with localized expressions. Strikingly, all identified genes were also induced in the regenerating adult fin, which has a different tissue origin from the larval fin fold. This result supports the commonality of regeneration irrespective of tissue type and stage. Importantly, our analysis suggested that the regenerating tissue had many more compartments than generally assumed ones, the blastema and wound epidermis. By pharmacological and genetic approaches, we further evaluated functional involvement of induced molecules. Inhibition of Mmp9 function impaired proper morphological restoration without disturbing cell proliferation. Genetic mutations of blastema genes, hspa9 and smarca4, disrupted the fin fold regeneration by impairing the blastema cell proliferation. Thus, our results demonstrate that the regeneration model of juvenile zebrafish offers a powerful assay to dissect the regeneration processes.


Is cigarette smoking a gateway to alcohol and illicit drug use disorders? A study of youths with and without attention deficit hyperactivity disorder.
The goal of this study was to assess whether cigarette smoking is a gateway drug for subsequent alcohol and illicit drug abuse and dependence in youth with Attention Deficit Hyperactivity Disorder (ADHD), and to test if this association is stronger in ADHD youth relative to controls. We used data from a case-control family study of female youth with and without ADHD. We studied 97 ADHD and 203 control youth of both sexes, aged at least 12 years. We assessed ADHD, smoking, and substance use status using structured diagnostic interviews. We tested the association between cigarette smoking and subsequent substance use outcomes using Cox proportional hazard regression models. ADHD youth who smoked cigarettes (n = 15) were significantly more likely to subsequently use alcohol and illicit drugs as well as to develop abuse and dependence compared to ADHD youth who did not smoke (n = 76; p < .05). These results extend the gateway hypothesis to an ADHD sample and provide evidence that this effect may be particularly robust in ADHD youth. If replicated in larger, community-based samples, these findings have important public health consequences, and underscore the already pressing need to prevent smoking in ADHD children.


Predicting sugar intake using an extended theory of planned behavior in a sample of adolescents: The role of habit and self-control.
High levels of sugar intake are associated with multiple maladaptive health outcomes in adult and younger populations. Identifying the psychological determinants of sugar intake in adolescents, and the processes involved, may help identify potentially modifiable targets and inform intervention development. We tested the predictions of an extended theoretical model based on the theory of planned behavior (TPB), which specified social cognition constructs, habit, and self-control as correlates of sugar intake in an adolescent sample. Adolescents aged 12 to 14 years (N = 88) recruited via a survey panel company and consenting to participate in the study completed online self-report measures of constructs from the TPB alongside measures of habit and self-control. One month later, participants completed a follow-up measure of free-sugar intake. Hypothesized effects of our proposed extended model were tested using partial least squares structural equation modeling. We found statistically significant effects of attitude, subjective norm, and perceived behavioral control on sugar intake intentions. We also found significant effects of habit and self-control on sugar intake measured at follow-up, but no effect for intention. Perceived behavioral control moderated the intention-behavior relationship such that intention effects on behavior were larger when perceived behavioral control was high. However, self-control did not moderate the intention-behavior relationship. Results indicate that sugar intake in this sample was a function of habits and self-control, and the effect of sugar intake intentions was conditional on perceived behavioral control. Results contribute to an evidence base of determinants and associated processes that relate to sugar intake in adolescents and may signal potentially modifiable targets for intervention.


Whole-genome analysis of haemophilus influenzae invasive strains isolated from Campinas state University hospital. An epidemiological approach 2012 - 2019 and ancestor strains.
Thirteen Haemophylus influenzae invasive strains isolated from patients at Clinical Hospital of State University of Campinas, from May 2013 through August 2019, was submitted to Illumina genome sequencing HiSeq platform. Further in silico analysis of serogroup and Multi Locus Sequence Typing (MLST) from whole DNA sequencing had demonstrated the actual clonal distribution in the Campinas Metropolitan region. Thus, results showed the existence of a new ST Haemophilus influenzae found in the Brazilian territory and an increase of strains belonging to serogroup a (three strains also belonging to ST23). In conclusion, we observed an increase of non-typable H. influenzae (NTHi) and a strain involved in invasive diseases in the Campinas - São Paulo region after frequent detection of those serotypes and genotypes in other Brazilian regions.


A unique poly(A) tail profile uncovers the stability and translational activation of TOP transcripts during neuronal differentiation.
Cell differentiation is associated with global changes in translational activity. Here, we characterize how mRNA poly(A) tail processing supports this dynamic. We observe that decreased translation during neuronal differentiation of P19 cells correlates with the downregulation of 5'-terminal oligopyrimidine (TOP) transcripts which encode the translational machinery. Despite their downregulation, TOP transcripts remain highly stable and show increased translation as cells differentiate. Changes in TOP mRNA metabolism are reflected by their accumulation with poly(A) tails ∼60-nucleotide (nt) long. The dynamic changes in poly(A) processing can be partially recapitulated by depleting LARP1 or activating the mTOR pathway in undifferentiated cells. Although mTOR-induced accumulation of TOP mRNAs with tails ∼60-nt long does not trigger differentiation, it is associated with reduced proliferation of neuronal progenitors. We propose that while TOP mRNAs are transcriptionally silenced, their post-transcriptional regulation mediated by a specific poly(A) processing ensures an adequate supply of ribosomes to complete differentiation.


The effect of E-5842, a sigma receptor ligand and potential atypical antipsychotic, on Fos expression in rat forebrain.
We examined the ability of E-5842 (4-(4-fluorophenil)-1,2,3,6- tetrahydro-1-[4-(1,2,4-triazol-1-il)butyl] pyridine citrate), a sigma receptor ligand, to increase Fos protein expression in regions of rat forebrain. An acute administration of E-5842 increased levels of Fos in the medial prefrontal cortex and the nucleus accumbens, without affecting the levels of the protein in the striatum, an effect very similar to that of clozapine. Our results suggest that E-5842 may be an atypical antipsychotic with low propensity to produce extrapyramidal side-effects.


Structural and mutational studies suggest key residues to determine whether stomatin SPFH domains form dimers or trimers.
Stomatin is a major integral membrane protein in human erythrocytes. In a form of hemolytic anemia known as hereditary stomatocytosis, stomatin is deficient in the erythrocyte membrane due to mis-trafficking. It is a member of stomatin, prohibitin, flotillin, and HflK/C (SPFH) domain proteins, and SPFH proteins could function as membrane-bound oligomeric scaffolding proteins in lipid rafts. The previously determined structure of the SPFH domain of Pyrococcus horikoshii (Ph) stomatin formed a trimer, whereas that of mouse stomatin formed a dimer. To elucidate the difference of oligomerization state, structural and chromatographic analyses using Ph stomatin were performed, and the key residues were suggested to determine whether SPFH domains form dimers or trimers. From gel-filtration analyses, PhStom (56-234) formed a trimer or tetramer, whereas PhStom (63-234) and PhStom (56-234) K59S formed a dimer. The residues 56-62, particularly Lys59, were involved in trimerization. Based on the crystal structure of PhStom (63-234), it formed a banana-shaped dimer, as observed in mouse stomatin. Thus, residues 162-168 are involved in dimerization. This study provides important insight into the molecular function and oligomerization state of stomatin.


Prognostic ability of the German version of the STarT Back tool: analysis of 12-month follow-up data from a randomized controlled trial.
Stratified care is an up-to-date treatment approach suggested for patients with back pain in several guidelines. A comprehensively studied stratification instrument is the STarT Back Tool (SBT). It was developed to stratify patients with back pain into three subgroups, according to their risk of persistent disabling symptoms. The primary aim was to analyse the disability differences in patients with back pain 12 months after inclusion according to the subgroups determined at baseline using the German version of the SBT (STarT-G). Moreover, the potential to improve prognosis for disability by adding further predictor variables, an analysis for differences in pain intensity according to the STarT-Classification, and discriminative ability were investigated. Data from the control group of a randomized controlled trial were analysed. Trial participants were members of a private medical insurance with a minimum age of 18 and indicated as having persistent back pain. Measurements were made for the risk of back pain chronification using the STarT-G, disability (as primary outcome) and back pain intensity with the Chronic Pain Grade Scale (CPGS), health-related quality of life with the SF-12, psychological distress with the Patient Health Questionnaire-4 (PHQ-4) and physical activity. Analysis of variance (ANOVA), multiple linear regression, and area under the curve (AUC) analysis were conducted. The mean age of the 294 participants was 53.5 (SD 8.7) years, and 38% were female. The ANOVA for disability and pain showed significant differences (p < 0.01) among the risk groups at 12 months. Post hoc Tukey tests revealed significant differences among all three risk groups for every comparison for both outcomes. AUC for STarT-G's ability to discriminate reference standard 'cases' for chronic pain status at 12 months was 0.79. A prognostic model including the STarT-Classification, the variables global health, and disability at baseline explained 45% of the variance in disability at 12 months. Disability differences in patients with back pain after a period of 12 months are in accordance with the subgroups determined using the STarT-G at baseline. Results should be confirmed in a study developed with the primary aim to investigate those differences.


Pertussis: History of the Disease and Current Prevention Failure.
Pertussis or whooping cough has been given many names over the centuries. It was first recognized in the Middle Ages and since then various epidemics have been described. Jules Bordet and Octave Gengou isolated Bordetella pertussis, a causative agent for whooping cough, in Paris more than 100 years ago, which created an excellent opportunity to invent a vaccine. In 1914 the whole-cell pertussis vaccine was invented, then in the 1940s it was combined with tetanus and diphtheria toxoids to become DTP and it became widely available. A successive decrease in the incidence of the disease has since been observed. The vaccine has been about 80 % effective in preventing serious disease and death from pertussis. The disadvantage is that the vaccine offers protection for 5-10 years after the last dose of the full vaccination course. The second issue is the question of how to prevent side effects of the whole-cell vaccine. In the 1990s, the acellular vaccine was introduced in the US and gradually replaced the whole-cell vaccine. About 10 years later, a possible failure with the new vaccine has been observed, that is a lack of long-term protection. Nowadays, both vaccines are used, with the acellular vaccine being vastly predominant in most developed countries. Pertussis incidence has increased since the 1980s, but new prevention strategies include booster doses for specific age groups.


Luteolin ameliorates depression-like behaviors by suppressing ER stress in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly population. Inflammation plays an important role in AD, as microglia respond to several pathological insults, such as Aβ, and exert protective homeostatic functions (anti-inflammatory) and detrimental inflammatory functions (proinflammatory). During the development of AD, chronic inflammation that accompanies aging causes microglial priming, a state of hyperactivation in response to stimulation, indicating that suppressing microglial priming may be a therapeutic intervention for AD. Endoplasmic reticulum (ER) stress is crucial for inflammation through NF-kB and inflammasome activation. To identify natural flavonoids that regulate ER stress, a DNA microarray was performed using the brains of AD model mice after long-term intake of quercetin, after which the connectivity map (CMap) assay was carried out. We found that luteolin suppresses lipopolysaccharide (LPS)-induced interleukin 1β (IL1β) expression by inhibiting ER stress. Immunohistochemical analyses showed that CD68 levels were reduced in the brain after intraperitoneal injection of luteolin in a mouse model of AD, suppressing IL1β production. As shown by behavioral analyses using the tail suspension test (TST) and forced swimming test (FST), depression-like behaviors were ameliorated in luteolin-treated AD model mice. These findings indicate that luteolin prevents ER stress to suppress microglial activation in the brain, improving individual activity.


[A nomogram for determination of "midparents height" and for correction of the height of children refering to the stature of their parents (author's transl)].
A monomgram is given to find graphically the mean between the stature of the father and the stature of the mother (midparents height) and to correct (in an additive or reducing manner) the height of children of a certain age refering to their midparents height. Using such correction terms may be an approximative method to exclude the genetic factors of growth if one wishes to compare groups of children growing up in different environments.


Central distribution and efferent origins of facial nerve branches in the chicken.
The central afferent distribution and the origins of visceromotor and somatomotor components of greater superficial petrosal (GSP), chorda tympani (CT), and hyomandibular (Hy) branches of the facial nerve were analyzed by the transganglionic and retrograde transport of horseradish peroxidase. Labelled sensory afferent fascicles of the GSP collected dorsomedial to the spinal trigeminal complex and passed caudally as the tractus solitarius. Fine-grain terminal fields were evident in ipsilateral n. sensorius n. facialis, nuclei ventrolateralis anterior (Vla), centralis anterior and presulcalis anterior of the solitary complex, and n. glossopharyngei et n. motorius dorsalis nervi vagi (n. IX-X). Minor contralateral projections to these nuclei occasionally were observed. CT sensory afferents exhibited similar ipsilateral projections, and specifically, the projection to Vla was qualitatively sparser than that from the GSP. Small multipolar and spindle-shaped somata of visceromotor n. salivatorius were labelled retrogradely from the GSP and CT. Large, oval somatomotor cells of the three subdivisions of the facial motor nucleus were labelled retrogradely from Hy, with no evidence of sensory afferent or visceromotor connections.


Prophylaxis of metastases formation by prolonged non-specific immunostimulation associated with heparin therapy.
In rats with Ehrlich ascites tumors, prolonged non-specific immunostimulation with a polymicrobial preparation significantly reduced metastases. Prolonged anticoagulant therapy with heparin was also shown to reduce metastases. Combined prolonged therapy with both agents reduced metastases significantly more than therapy with either agent alone.


Population growth and predation interference between two species of predatory phytoseiid mites (Acarina: Phytoseiidae) in interactive systems.
Populations of two species of phytoseiid mite predators, Phytoseiulus persimilis Athias-Henriot and Amblyseius degenerans (Berlese), feeding on a tetranychid prey, Tetranychus pacificus McGregor, were allowed to grow separately as well as together on bush lima bean (Phaseolus lunatus Var.) arenas in the laboratory. The population plateau attained by P. persimilis was nearly 5 times higher than that for A. degenerans when each species was on separate leaf arenas. When they were on the same arena, P. persimilis was outcompeted by A. degenerans after about 70 days of population growth. When dispersal to other arenas was necessary for the predators to find prey in another experiment, P. persimilis survived well but not A. degenerans. The mechanisms underlying species displacement were explored further. The differential mortality of immature predators at different developmental stages due to interspecific predation was concluded to be responsible for the population decline of P. persimilis, and the decline of A. degenerans in another experiment was attributed to its sedentary tendency regardless of prey distribution and to the lack of alternative food sources in the system. The implications to biological control of mutual predation between predator species is discussed briefly.


Further evidence for association of the RGS2 gene with antipsychotic-induced parkinsonism: protective role of a functional polymorphism in the 3'-untranslated region.
RGS2 (regulator of G-protein signaling 2) modulates dopamine receptor signal transduction. Functional variants in the gene may influence susceptibility to extrapyramidal symptoms (EPS) induced by antipsychotic drugs. To further investigate our previous report of association of the RGS2 gene with susceptibility to antipsychotic-induced EPS, we performed a replication study. EPS were rated in 184 US patients with schizophrenia (115 African Americans, 69 Caucasian) treated for at least a month with typical antipsychotic drugs (n=45), risperidone (n=46), olanzapine (n=50) or clozapine (n=43). Six single nucleotide polymorphisms (SNPs) within or flanking RGS2 were genotyped (rs1933695, rs2179652, rs2746073, rs4606, rs1819741 and rs1152746). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. Our results indicate association of SNP rs4606 with antipsychotic-induced parkinsonism (AIP), as measured by the Simpson Angus scale, in the overall sample and in the African-American subsample, the G (minor) allele having a protective effect. ORs for AIP among rs4606 G-allele carriers were 0.23 (95% CI 0.10-0.54, P=0.001) in the overall sample, and 0.20 (0.07-0.57, P=0.003) in the African-American subsample. In the previously studied Israeli sample the OR was 0.31 (0.11-0.84, P=0.02). We completely sequenced the RGS2 gene in nine patients with AIP and nine patients without, from the Israeli sample. No common coding polymorphisms or additional regulatory variants were revealed, suggesting that association of the rs4606 C/G polymorphism with AIP is biologically meaningful and not a consequence of linkage disequilibrium with another functional variant. Taken together, the findings of the current study support the association of RGS2 with AIP and focus on a possible protective effect of the minor G allele of SNP rs4606. This SNP is located in the 3'-regulatory region of the gene, and is known to influence RGS2 mRNA levels and protein expression.


Estrogen-induced post-transcriptional modulation of c-myc proto-oncogene expression in human breast cancer cells.
The effects of estradiol (E2) on c-myc proto-oncogene expression were studied in the estrogen receptor (ER)-positive human breast cancer cell line, MCF-7. A biphasic modulation in c-myc mRNA levels occurs during the first 24 h of E2 (1 nM) exposure and in the absence of changes in MCF-7 culture growth, with transcript levels rising 4-6-fold within 1 h, returning to near base-line level after 3-6 h, and increasing again after 24 h of exposure. In contrast, the growth-inhibiting antiestrogen, tamoxifen (1 microM), reduces c-myc to 20% of the pretreatment level within 3-6 h of exposure, and this early decline is followed by a gradual return toward base-line level after continuous 72-h treatment. In ER-negative cells there is no change in c-myc expression following E2 exposure. MCF-7 nuclear runon assays show that c-myc transcription rates remain unchanged from base line for 24 h after E2 administration; as well, cycloheximide inhibition of protein synthesis superinduces c-myc expression and prevents E2 modulation of transcript levels. These results indicate that post-transcriptional modulation of c-myc by E2 is mediated by a labile degradative protein or otherwise dependent on active protein synthesis. We also developed MCF/nm and MCF/dm sublines by transfecting normal cells with human c-myc exons 2-3, transcriptionally driven by a retroviral long terminal repeat. Expression of the transfected c-myc genes in these sublines remains constant and elevated 10-fold, while transcript levels from the endogenous proto-oncogene continue to be modulated by E2. These findings suggest that in ER-positive breast cancer cells, E2 can modulate c-myc mRNA levels by a post-transcriptional mechanism that depends on gene sequences upstream from c-myc exon 2.


cDNA microarray analysis of autoimmune hepatitis, primary biliary cirrhosis and consecutive disease manifestation.
While autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) usually have distinct clinical manifestations, some patients present with features of both conditions. Using cDNA microarrays, we analyzed and compared gene expression profiles in 8 patients with AIH, 9 with PBC, 8 with chronic hepatitis C (CHC), 8 with non-alcoholic steatohepatitis (NASH) and 9 with normal livers. We subsequently applied this method to a tissue sample from a 61-year-old woman with overlapping features of both AIH and PBC. A 61-year-old woman was admitted to our hospital for evaluation of elevated serum alkaline phosphatase. A liver biopsy showed accumulation of mononuclear cells around the bile duct cells, a feature characteristic of chronic non-suppurative destructive cholangitis (CNSDC). Three years later, her serum alanine aminotransferase (ALT) level had increased, and a liver biopsy demonstrated evidence of a severe form of hepatitis. A cDNA microarray analysis of both biopsies identified the molecular events associated with her altered histology. The expression profile of this patient, which was originally different from that of the other PBC patients, changed to an AIH pattern. Our results suggest that this patient has characteristics of both AIH and PBC.


LncRNA MEG3 aggravates adipocyte inflammation and insulin resistance by targeting IGF2BP2 to activate TLR4/NF-κB signaling pathway.
Recently, emerging evidence has shown that LncRNA MEG3 is involved in adipocyte inflammation and insulin resistance progression, however, the specific mechanism of action remains unclear. In this study, we found that LncRNA MEG3 expression was increased in TNF-α stimulated 3T3-L1 mature adipocytes, and inflammatory factors IL-6 and MCP-1 secretion levels were increased, cell apoptosis and caspase3 activity was enhanced, ROS content was increased, and iNOS protein expression was increased. Moreover, TNF-α treatment attenuated glucose uptake, promoted triglyceride accumulation, inhibited GLUT4 protein expression at the plasma membrane, and reduced the phosphorylation levels of AMPK and ACC in the cells. Interestingly, we found that transfection of si-MEG3 reversed TNF-α caused inflammatory injury and insulin resistance of 3T3-L1 mature adipocytes. Next, we found that IGF2BP2 is an RNA binding protein of LncRNA MGE3 and transfection of si-IGF2BP2 reversed TNF-α caused inflammatory injury and insulin resistance in 3T3-L1 mature adipocytes, the same effects as transfection of si-MEG3. Mechanistically, LncRNA MGE3 was able to aggravate adipocyte inflammatory injury and dysregulation of insulin sensitivity by activating TLR4 pathway through upregulating the protein expression of IGF2BP2. In vivo findings showed that HFD mice with knockdown of MEG3 had reduced body weight, lower glucose concentrations and insulin levels in plasma, decreased inflammatory factors secretion, and reduced MEG3 and IGF2BP2 expression in epididymal adipose tissues and reduced fat accumulation in mice compared with HFD mice. Our results indicate that LncRNA MEG3 can aggravate chronic inflammation and insulin resistance in adipocytes by activating TLR4/NF-κB signaling pathway via targeting IGF2BP2.


In vitro assay to estimate tea astringency via observing flotation of artificial oil bodies sheltered by caleosin fused with histatin 3.
Astringency, a sensory characteristic of food and beverages rich in polyphenols, mainly results from the formation of complexes between polyphenols and salivary proteins, causing a reduction of the lubricating properties of saliva. To develop an in vitro assay to estimate the astringency of oolong tea infusion, artificial oil bodies were constituted with sesame oil sheltered by a modified caleosin fused with histatin 3, one of the human salivary small peptides. Aggregation of artificial oil bodies was induced when they were mixed with oolong tea infusion or its major polyphenolic compound, (-)-epigallocatechin gallate (EGCG) of 100μM as observed in light microscopy. The aggregated artificial oil bodies gradually floated on top of the solution and formed a visible milky layer whose thickness was in proportion to the concentrations of tea infusion. This assay system was applied to test four different oolong tea infusions with sensory astringency corresponding to their EGCG contents. The result showed that relative astringency of the four tea infusions was correlated to the thickness of floated artificial oil bodies, and could be estimated according to the standard curve generated by simultaneously observing a serial dilution of the tea infusion with the highest astringency.


Genetic toxicology testing of 41 industrial chemicals.
41 compounds or mixtures of diverse structure and application have been tested for genotoxic activity. The materials were tested in bacterial mutation assays, in Saccharomyces cerevisiae JD1 for mitotic gene conversion and in a cultured rat-liver cell line for structural chromosome damage. 11 compounds were bacterial mutagens, 4 induced mitotic gene conversion in yeast and 5 were positive in the chromosome assay. 5 of the materials were positive in bacteria only and 2 compounds induced chromosome damage in cultured cells in the absence of mutation in bacteria or gene conversion in yeast. The materials were tested over a 5-year period and the performance and evolution of the 3 assays during this time is evaluated. The results are considered in relation to the structure of the chemicals and the genotoxicity of related compounds.


Why does the cardiac force-velocity relationship not follow a Hill hyperbola? Possible implications of feedback loops involved in cardiac excitation-contraction coupling.
1. If cardiac force-velocity (PV) relationships are determined in a rhythmically beating isolated preparation by progressively changing afterloads, the PV curves obtained exhibit a characteristic nonhyperbolic shape with an upward convexity in the force domain close to P0. It was suggested by others that this might be due to contractile element (CE) shortening against series elastic component (SEC) and/or the early decay of the active state at isometric peak tension. 2. The present investigation performed in isolated cat papillary muscles demonstrates that neither CE shortening against SEC nor the variation of the intensity of the active state can fully account for the nonhyperbolic shape of cardiac PV curves. 3. On the other hand large parts of the remaining deviation could be eliminated if the "progressive loading sequence" (PLS) was replaced for an "interpolated loading sequence" (ILS). Here, the muscle contracts under steady state conditions either isometrically or isotonically (zero load). Single afterloaded test contractions are interpolated after every 10th beat. 4. It is concluded that the nonhyperbolic shape of cardiac PV curves, determined by progressively changing afterloads, is the expression of at least four factors: (i) the existence of displacement dependent variation of excitation-contraction coupling (including the contraction-excitation-contraction recoupling loop), (ii) CE shortening against non CE bound SEC, (iii) a variable active state and (iiii) a fourth unknown mechanism.


CD44-mediated uptake and degradation of hyaluronan.
Hyaluronan turnover occurs systemically from the lymph and serum as well as locally by the same cells responsible for its synthesis. Local turnover involves receptor-mediated uptake and delivery to lysosomes. Of the many hyaluronan binding proteins/receptors known, the participation of CD44 in the internalization of hyaluronan has been best characterized. Some fraction of the hyaluronan bound to CD44 becomes internalized and delivered to lysosomes by a mechanism that is not dependent on clatherin, caveolae or pinocytosis. In cells such as chondrocytes, anabolic and catabolic cytokines can alter the activity of CD44 toward hyaluronan internalization. However, the mechanism of cellular regulation remains unclear. Regulation may involve the participation of alternatively spliced isoforms of CD44, changes in CD44 phosphorylation, changes in cytoskeletal binding proteins or, the activity or extracellular proteolytic activity.


Incontinentia pigmenti (IP) and r(X). Tentative mapping of the IP locus to the X juxtacentromeric region.
A 45,X/46,X,r(X) mosaicism was observed in an incontinentia pigmenti (Bloch-Sulzberger form) female patient, with mental retardation, short stature, and minor dysmorphisms. This observation is compatible with the regional assignment of the incontinentia pigmenti locus to the juxta-centromeric region of the X, the r(X) being of very small size.


ControL'Asma Project: new insights.
The Italian Society of Paediatric Allergy and Immunology has developed the project "ControL'Asma," a nationwide study involved ten third-level pediatric allergy clinics across Italy. The first findings of the "ControL'Asma" project showed that asthma was more frequent in males, had an early onset and allergic phenotype with very frequent rhinitis comorbidity, uncontrolled, and partly controlled asthma affected about the half of subjects, and the assessment of asthma symptom perception by VAS could be a reliable tool in the asthma management.


Magnetic resonance imaging of the craniovertebral junction in early rheumatoid arthritis.
To assess the involvement of the atlantoaxial joint in patients with early rheumatoid arthritis (ERA) and to elucidate the risk profile for the individual patient. Consecutive ERA patients (disease duration < 12 months) were included in our study. A cervical spine magnetic resonance imaging (MRI) and X-rays (cervical spine, hands, wrists, and feet) were performed in all patients. The MRI features were correlated with clinical, radiological, and biochemical variables. Fifty patients (13 men and 37 women) with a mean age of 58.2 years (range, 36-79 years) were included in the study. In 12 (24%) patients were detectable MRI findings suggestive of the craniovertebral junction involvement. Compared with patients without cervical involvement, the patients with atlantoaxial synovitis showed a significantly higher anti-citrullinated protein antibodies (ACPA) titer [mean 200.25 UI (SD 262.44) vs. mean 22.05 (SD 40.21) (p < 0.001)]; a worse Disease Activity Score 44 joints (DAS44) [mean 5.72 (SD 0.44) vs. mean 4.52 (SD 0.53) (p < 0.001)]; a worse Health Assessment Questionnaire Disability Index (HAQ-DI) [mean 1.55 (SD 0.37) vs. mean 1.09 (SD 0.33) (p < 0.001)], and a higher Simple Erosion Narrowing Score (SENS) [mean 15.83 (SD 4.52) vs. mean 7.71 (SD 3.43) (p < 0.001)]. The multivariate analysis revealed a meaningful relationship between atlantoaxial synovitis and ACPA, DAS44, and the presence of an erosive disease. The craniovertebral junction is frequently involved in ERA patients. ACPA, high disease activity, and erosive disease at baseline are predictors of atlantoaxial involvement.


Dental patients' awareness and knowledge in using dental implants as an option in replacing missing teeth: A survey in Riyadh, Saudi Arabia.
The purpose of this survey was to assess the level, sources, and need for information about dental implants among a selected sample of dental patients in Riyadh, Saudi Arabia. Patients' knowledge and awareness in using dental implants as an option in replacing missing teeth were evaluated through a standardized self- explanatory questionnaire distributed in two places in Riyadh: Military Hospital and College of Dentistry, King Saud University (Darraiyah campus). The questionnaires were handed to the patients during their regular dental visits. A total of 379 subjects were included in this survey. The results of this study indicate that 66.4% of the subjects knew about dental implants. The subjects' friends and their relatives were the main source of information about dental implants for 31.5% of the subjects, and dentists were the secondary source for 28.3% of the sample. About 82.4% of the subjects need more information about dental implants and 85.2% of them chose the dentist to be the desired source for such information, followed by the internet in 28.5% of the cases. Almost 74.4% of those surveyed did not know if their regular dentists use dental implants. High cost was the major factor in preventing patients from choosing implants in 86.5% of the cases while the long treatment time and fear of surgery was the factor in 71% and 68.6% of the subjects, respectively. The results of this survey showed an acceptable level of awareness about dental implants among a selected sample of dental patients in Riyadh. It also showed the need for providing more general and accurate information to the patients about this treatment modality.


Comparison between the WHO-CFICPS and the PRISMA classification of safety-related events in a radiation oncology department.
Describing Safety-Related Events (SREs) in a radiotherapy (RT) department and comparing WHO-CFICPS (World Health Organization's Conceptual Framework For The International Classification For Patient Safety) and PRISMA (Prevention and Recovery Information System for Monitoring and Analysis) methods for classifying SREs. From February 2017 to October 2020, two Quality Managers (QMs) randomly classified 1173 SREs using 13 incident types of WHO-CFICPS. The same two QMs, reclassified the same SREs according to 20 PRISMA incident codes. Statistical analysis was performed to assess the association between the 13 incident types of WHO-CFICPS and the 20 PRISMA codes. The chi-squared and post-hoc tests using adjusted standardized residuals were applied to detect the association between the two systems. There was a significant association between WHO-CFICPS incident types and PRISMA codes (P < 0.001). Ninety-two percent of all SREs were categorized using 4 of 13 WHO-CFICPS incident types including Clinical Process/Procedure (n = 448, 38.2%), Clinical Administration (n = 248, 21.1%), Documentation (n = 226, 19.2%) and Resources/Organizational Management (n = 15,613.3%). According to PRISMA classification, 14 of the 20 codes were used to describe the same SREs. PRISMA captured 41 Humans Skill Slips from 226 not better defined WHO-CFICPS Documentation Incidents, 38 Human Rule-based behaviour Qualification from not better defined 447 Clinical Process/Procedure and 40 Organization Management priority events from 156 not better defined WHO-CFICPS Resources/Organizational Management events (P < 0.001). Although there was a significant association between WHO-CFICPS and PRISMA, The PRISMA method provides a more detailed insight into SREs compared to WHO-CFICPS in a RT department.


User perspectives on the future of mobility assistive devices: Understanding users' assistive device experiences and needs.
Current assistive devices are inadequate in addressing the needs of some people living with impaired mobility. This study explored the experiences of living with impaired mobility in relation to how wearable assistive adaptive and rehabilitative technologies may improve their quality of life. A cross-case study approach was adopted; the case being defined as the experience of impaired mobility. Semi-structured interviews were utilised. The sample (n = 8) was purposefully selected to have impaired mobility due to stroke, age-related frailty, or lower limb amputation. From the interview transcripts, in-depth case illustrations were written to provide personal stories and thematic analysis was carried out to provide a cross-case analysis. There were two overarching themes: lifestyle changes; and wishes and desires for assistive devices. There were shared experiences across participant groups, such as falls and fear of falling. All participants identified a wish for increased speed of walking. However, the reasons for their difficulties differed depending on personal factors and their condition. Participants wanted devices to be adjustable to their perceived ability on a day-to-day basis. Although common concerns and impacts of living with impaired mobility were apparent, individuals have unique requirements that should inform the design of assistive technology devices.


Kindling alters entorhinal cortex-hippocampal interaction by increased efficacy of presynaptic GABA(B) autoreceptors in layer III of the entorhinal cortex.
We studied the effect of kindling, a model of temporal lobe epilepsy, on the frequency-dependent information transfer from the entorhinal cortex to the hippocampus in vitro. In control rats repetitive synaptic activation of layer III projection cells resulted in a frequency dependent depression of the synaptic transfer of action potentials to the hippocampus. One-to-two-days after kindling this effect was strongly reduced. Although no substantial change in synaptic inhibition upon single electrical stimulation was detected in kindled rats, there was a significant depression in the prolonged inhibition following high frequency stimulation. In kindled animals, paired-pulse depression (PPD) of stimulus-evoked IPSCs in layer III neurons was significantly stronger than in control rats. The increase of PPD is most likely caused by an increased presynaptic GABA(B) receptor-mediated autoinhibition. In kindled animals activation of presynaptic GABA(B) receptors by baclofen (10 microM) suppressed monosynaptic IPSCs significantly more than in control rats. In contrast, activation of postsynaptic GABA(B) receptors by baclofen was accompanied by comparable changes of the membrane conductance in both animal groups. Thus, in kindled animals activation of the layer III-CA1 pathway is facilitated by an increased GABA(B) receptor-mediated autoinhibition leading to an enhanced activation of the monosynaptic EC-CA1 pathway.


Glutamate uptake is reduced in prefrontal cortex in Huntington's disease.
Huntington's disease (HD) is caused by a CAG repeat expansion in the HD gene, but how this mutation causes neuronal dysfunction and degeneration is unclear. Inhibition of glutamate uptake, which could cause excessive stimulation of glutamate receptors, has been found in animals carrying very long CAG repeats in the HD gene. In seven HD patients with moderate CAG expansions (40-52), repeat expansion and HD grade at autopsy were strongly correlated (r=0.88, p=0.0002). Uptake of [(3)H]glutamate was reduced by 43% in prefrontal cortex, but the level of synaptic (synaptophysin, AMPA receptors) and astrocytic markers (GFAP, glutamate transporter EAAT1) were unchanged. Glutamate uptake correlated inversely with CAG repeat expansion (r= -0.82, p=0.015). The reducing agent dithiothreitol improved glutamate uptake in controls, but not in HD brains, suggesting irreversible oxidation of glutamate transporters in HD. We conclude that impairment of glutamate uptake may contribute to neuronal dysfunction and degeneration in HD.


Effects of ecological factors on the antioxidant potential and total phenol content of Scrophularia striata Boiss.
Scrophularia striata, commonly known as figwort, is one of the most important medicinal plants that mainly grows in cold regions of the Zagros Mountains (West of Iran). Although the chemical composition of this plant species has not yet been explored, people living in Ilam province (W Iran) have used it for many years to treat different illnesses. The present study aims to analyze the effect of some ecological factors on the antioxidant potential and the amount of phenol present in this plant species, using a random factorial design with two factors (elevation and region) and three replicates. The fruits of the plant were gathered from three different elevations. They were collected from three regions of the Ilam province (Badreh, Dareshahr, and Dehloran) in June 2016, when the fruits appear. Moreover, to analyze different soil chemical and physical features, soil samples were gathered from a depth of 0.5 m under the shrubs. The antioxidant action of the methanol extract from the plant samples and the total amount of phenol compounds were measured using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and the Folin-Ciocalteu method, respectively. The results showed that the effects of site and elevation, and the interaction between these factors, on the antioxidant potential and total phenol amount were significant with a probability of error of 1%. The maximum extract efficiency (19.37 ± 3.07%), antioxidant potential (126.5656 ± 0.96 µg/mL), and total amount of phenol (55.7689 ± 3.17 µg/mL) were obtained from Dareshahr at an elevation of 600 m above mean sea level. The minimum amount of total phenol (24.6544 ± 3.21 µg/ml) was recorded at the lowest elevation of Badreh, at which phosphorus, potassium, organic carbon, organic material, nitrogen, acidity, lime, and silt were present at the lowest amount. However, the antioxidant activity and total amount of phenol had a strong direct correlation in the two districts of Dareshahr and Badreh, but were reversely and strongly correlated in Dehloran. Therefore, it can be stated that Scrophularia striata has the potential for antioxidant activity, however, the complexity of the effect of ecological factors on one hand, and the emergence of different chemical processes in the plant under such effects on the other hand, has led to the synthesis of different compounds with antioxidant potential in the plant in different regions.


Cyclin D1 is significantly associated with stage of tumor and predicts poor survival in endometrial carcinoma patients.
Cyclin D1 overexpression has been described to have oncogenic role and association with diagnosis, prognosis and survival in various tumors. This study will describe the immunohistochemical phenotype of cyclin D1, and investigate the correlation between these patterns of expression and clinicopathological parameters of endometrial carcinomas, to conclude the clinical relevance of cyclin D1 expression in the evolution of endometrial neoplasms. This study employed 101 endometrial tissue samples which include 71 endometrial carcinomas and thirty normal and benign endometrium cases. All these tissue samples were used in the assembly of tissue microarrays which have been utilized afterward in immunohistochemistry staining to detect cyclin D1 expression. Forty (56.3%) cases of endometrial carcinomas showed brown nuclear expression of cyclin D1 including 36 (61%) cases of endometrioid carcinomas, and 3 (33.3%) cases of serous carcinomas. Twenty three (76.6%) cases of control group demonstrated nuclear expression. High score cyclin D1 immunohistochemical staining has been significantly linked with patient age (P=0.0001). Large proportion of high score cyclin D1 immunohistochemical staining was observed in females who are <40years of age while high proportions of negative staining were observed in older age groups. Histologic type of tissue was also significantly related to cyclin D1 immunohistochemical staining (P-value=0.0001), high staining is more common in normal proliferative and secretory endometrium while serous carcinoma is more prevalent with negative staining. Stage of tumor was significantly associated with cyclin D1 immunohistochemical staining (P-value=0.029), proportion of stage III and IV are higher in negative cyclin D1 immunostaining. Significantly higher proportion of high score cyclin D1 immunostaining is observed in controls while higher proportion of negative cyclin D1 immunostaining is observed among carcinoma cases (P-value=0.0001). No significant associations between cyclin D1 immunohistochemical staining and grade, recurrence and alive status were observed. Significant different survival distributions were observed (P-value=0.011) and poor survival behavior was correlated with negative cyclin D1 immunohistochemical staining. In conclusion, greater frequency of cyclin D1 expression was revealed in normal endometrial tissues in comparison with carcinomas. The distribution pattern of cyclin D1 immunoexpression suggests poor prognoses in endometrial carcinoma patients.


Predictors of institutionalization in demented patients discharged from a rehabilitation unit.
The decision to place a patient with dementia in long-term care is complex and based on the patient's and the caregiver's characteristics, and on the sociocultural context. Most studies assessing predictors of nursing home placement focused primarily on the characteristics of either the patient, such as dementia severity and difficult behaviors, or the caregiver, such as subjective burden and health status. However, only a few studies comprehensively investigated how both a caregiver's and a patient's characteristics influence nursing home placement. To identify the patient's and the caregiver's characteristics that influence discharge to a nursing home in demented patients consecutively admitted to an intermediate care setting. Observational study of 214 patients with dementia consecutively admitted to a Rehabilitation Unit for Dementia in Northern Italy (length of stay 35.1 +/- 14.9 days). The main evaluated outcome was the final destination (home vs nursing home). In a multivariate logistic regression analysis, adjusted for age, gender, cognitive status, and behavioral disturbances, 4 predictors were associated with nursing home placement: living alone (OR 8.79, 95% CI 2.33-33.16; P = .001), degree of dementia severity (CDR, OR 1.69, 95% CI 1.02-2.83; P = .04), compromised functional status (Barthel index admission, OR 3.15, 95% CI 1.05-9.48; P = .04), and caregiver's burden (CBI, OR 2.89, 95% CI 1.15-7.29; P = .02). Data suggest that living alone, patient's functional impairment, severity of dementia, and caregiver's burden were independent predictors of institutionalization. The interaction between a patient's and a caregiver's characteristics has an important effect on the rate of nursing home placement in demented patients.


Teaching nursing history: the Redwood experience.
This paper traces the development of nursing history from the great names approach of the early 20th century to the new analytical directions represented by the work of Davies and Maggs. It discusses the relevance of the study of nursing history in the present climate. The author shares the experiences of incorporating nursing history into a pre-registration diploma programme and suggests ways of evaluating this course of study.


Occurrence of antibodies against gene products of the major histocompatibility complex in normal sera of diabetes-prone BB rats.
Natural antibodies were detected in normal sera of diabetes-prone rats of substrain dp BB/DK (19.5%), non-diabetes-prone ndp BB/PhiK (17.8%) and their ancestral randombred strain WOK (2.2-7.5%). These antibodies were haemagglutinins specifically reacting with antigenic products of the RT1.A region, mainly with products of RT1.Aa,d,f haplotypes. The possible causes of this unusual finding are discussed.


Retinal vascular endothelial growth factor induces intercellular adhesion molecule-1 and endothelial nitric oxide synthase expression and initiates early diabetic retinal leukocyte adhesion in vivo.
Leukocyte adhesion to the diabetic retinal vasculature results in early blood-retinal barrier breakdown, capillary nonperfusion, and endothelial cell injury and death. Previous work has shown that intercellular adhesion molecule-1 (ICAM-1) and CD18 are required for these processes. However the relevant in vivo stimuli for ICAM-1 and CD18 expression in diabetes remain unknown. The current study investigated the causal role of endogenous vascular endothelial growth factor (VEGF) and nitric oxide in initiating these events. Diabetes was induced in Long-Evans rats with streptozotocin, resulting in a two- to threefold increase in retinal leukocyte adhesion. Confirmed diabetic animals were treated with a highly specific VEGF-neutralizing Flt-Fc construct (VEGF TrapA(40)). Retinal ICAM-1 mRNA levels in VEGF TrapA(40)-treated diabetic animals were reduced by 83.5% compared to diabetic controls (n = 5, P < 0.0001). VEGF TrapA(40) also potently suppressed diabetic leukocyte adhesion in retinal arterioles (47%, n = 11, P < 0.0001), venules (36%, n = 11, P < 0.0005), and capillaries (36%, n = 11, P < 0.001). The expression of endothelial nitric oxide synthase (eNOS), a downstream mediator of VEGF activity, was increased in diabetic retina, and was potently suppressed with VEGF TrapA(40) treatment (n = 8, P < 0.005). Further, VEGF TrapA(40) reduced the diabetes-related nitric oxide increases in the retinae of diabetic animals. The inhibition of eNOS with N-omega-nitro-L-arginine methyl ester also potently reduced retinal leukocyte adhesion. Although neutrophil CD11a, CD11b, and CD18 levels were increased in 1-week diabetic animals, VEGF TrapA(40) did not alter the expression of these integrin adhesion molecules. Taken together, these data demonstrate that VEGF induces retinal ICAM-1 and eNOS expression and initiates early diabetic retinal leukocyte adhesion in vivo. The inhibition of VEGF bioactivity may prove useful in the treatment of the early diabetic retinopathy.


Polymorphisms in the H19 gene and the risk of lung Cancer among female never smokers in Shenyang, China.
Long non-coding RNA (lncRNA) H19 is a hot spot in tumor development, progression and metastasis. This study assessed the association between H19 genetic polymorphisms and the susceptibility of lung cancer. The case-control study was conducted to evaluate the association between four selected single nucleotide polymorphisms (rs217727, rs2107425, rs2735469 and rs17658052) in H19 gene and the risk of lung cancer. There were 556 female never smoking lung cancer patients and 395 cancer-free controls. Unconditional logistic regression analysis was used to analyze the associations between four SNPs and lung cancer risks by calculating the odds ratios and their 95% confidence intervals. The gene-environment interactions were assessed on both additive and multiplicative scales. Compared with carriers carrying homozygous CC genotype, there was a statistically significant increased risk of lung cancer for carriers of the rs2107425 TT genotype (odds ratio = 1.599, 95%CI = 1.106-2.313, P = 0.013). In both dominant and recessive models, significant associations were found between rs2107425 and lung cancer risk, and the corresponding odds ratios were 1.346 (1.022-1.774) and 1.400 (1.011-1.937), with P values 0.035 and 0.043, respectively. There was no significant correlation between lung cancer risk and rs2735469, rs217727 and rs17658052. Interaction analysis showed that their combined effects had a greater impact on lung cancer than individual effects of polymorphism and cooking smoke exposure. However, further analysis showed that the both additive model and the multiplicative model were not statistically significant. The polymorphism rs2107425 in H19 gene was associated with the risk of lung cancer among female who never smokes in Shenyang, China.


Coronary arteriography 1984-1987: a report of the Registry of the Society for Cardiac Angiography and Interventions. II. An analysis of 218 deaths related to coronary arteriography.
In a 42-month period, 218 deaths occurred in 222,553 patients undergoing coronary arteriography (0.098%). Age greater than 60 years, NYHA Class IV function, presence of left main coronary disease, and ejection fraction less than 30% all significantly increased the risk of the procedure. Sex and approach (brachial or femoral) used for the catheterization did not affect mortality. Since the SCAI report in 1982, the death rate has dropped significantly in high-risk patients. Low-risk patients (NYHA Class I or normal coronary arteries) who died generally were elderly or had associated valvular heart disease.


Can Deficiencies in Performance Be Identified Earlier in Surgical Residency? An Initial Report of a Surgical Trainee Assessment of Readiness Exam.
Identifying gaps in medical knowledge, patient management, and procedural competence is difficult early in surgical residency. We designed and implemented an end-of-year examination for our postgraduate year 1 residents, entitled Surgical Trainee Assessment of Readiness (STAR). Our objective in this study was to determine whether STAR scores correlated with other available indicators of resident performance, such as the American Board of Surgery in-training exam (ABSITE) and Milestone scores, and if they provided evidence of additional discriminatory value. Overall and component scores of the STAR exam were compared to the ABSITE and Milestone assessment scores for the 17 categorical residents that took the exam in 2016 and 2017. Harbor-UCLA Medical Center, a university-affiliated academic medical center. Seventeen categorical general surgery residents. The STAR Total Test Score (β = 2.77, p = 0.006) was an independent predictor of the ABSITE taken the same year, and components of the STAR were independent predictors of ABSITE taken the following year. The STAR Total Test Score was lowest in the 3 residents who had at least 1 low Milestone score assessed in the same year; and 2 of these 3 residents had at least 1 low Milestone score assigned the next year after STAR. Lastly, the Patient Care 1 and 2 Milestones assessed in the same year as STAR were uniformly scored as appropriate for level of training, yet the corresponding STAR component for those milestones demonstrated 3 residents as having deficiencies. We have created a multifaceted standardized STAR exam, which correlates with performance on the ABSITE and early milestone scores. It also appears to discriminate resident performance where milestone assessments do not. Further evaluation of the STAR exam with longer term follow-up is needed to confirm these initial findings.


Gaucher-like cells in juvenile GM1-gangliosidosis and in beta-thalassemia -- A histochemical and ultrastructural observation.
Peculiar storage cells appearing in bone marrow aspirates from a patient with juvenile GM1-gangliosidosis and from one with beta-thalassemia were examined light microscopically, histochemically and electron microscopically. Light microscopically, most of the storage cells closely resembled Gaucher cells pathognomonic for Gaucher's disease. The cytoplasm of the Gaucher-like cells contained numerous variable-shaped membrane-bound inclusions mostly arranged in a mosaic pattern and filled with fibrillar materials. Intermingled tubular structures were usually narrow as compared to those of the Gaucher cells. These ultrastructural differences of the stored materials between the Gaucher-like cells and Gaucher cells were more clearly substantiated by the high resolution electron microscopy with negative staining technique. Enzyme cytochemically, acid phosphatase activity was proved in or around the storage inclusions, suggesting their lysosomal origin. Histochemically, it might be suggested that the stored materials of the Gaucher-like cells in juvenile GMI-gangliosidosis were non-sulfated acid mucopolysaccharides and glycopeptides, whereas glycoproteins were the major component of the storage cells in beta-thalassemia. Possible mechanisms of storage in the Gaucher-like cells were discussed in both disorders.


Breast cancer adjuvant chemotherapy dosing in obese patients: dissemination of information from clinical trials to clinical practice.
Substantial variation in adjuvant breast cancer chemotherapy dosing in obese women suggests that there is uncertainty about optimal practices. The purpose of this study was to investigate variations in dose determinations in clinical trial protocols and publications over the last 3 decades as potential sources of this uncertainty. The National Cancer Institute database was used to identify protocols of breast cancer adjuvant chemotherapy conducted by cooperative groups between 1970-2000, and these protocols were then obtained directly from the cooperative groups. Dose determinations were categorized in each protocol and in published reports from each clinical trial. Fisher exact tests were used to compare the proportions of protocols that used full weight-based doses over time. Protocol-specified chemotherapy dosing was obtained for all of 44 eligible trials. A significant increase was identified in the use of full weight-based doses in the later time period compared with the earlier (P = .004; 2-sided Fisher exact test). A notable exception was 1 cooperative group that continues to require dose limitations for doxorubicin and cyclophosphamide in patients with a body surface area of more than 2.0 m(2). Regardless of publication date, published reports of clinical trials rarely provide information on use of full or limited weight-based doses. Variations in dose determinations among clinical trial protocols and lack of information on use of full weight-based doses in most publications are 2 likely sources of variation in chemotherapy dosing in obese women. Developing consensus and disseminating information on optimal chemotherapy dosing will likely reduce such variation and may improve survival among obese patients with breast cancer.


Diagnosis of patent ductus arteriosus by serendipity in the adult.
Seven patients with patent ductus arteriosus (PDA) were seen in our adult echocardiography laboratory. In five of seven patients the diagnosis was made on color Doppler when it was not suspected clinically. The diagnosis became apparent because of a turbulent retrograde jet seen on color Doppler in the main pulmonary artery. One of the patients had known congenital heart disease and heart surgery in the past, and the diagnosis of PDA was missed both on catheterization and in the operating room. PDA may be unsuspected in adult patients and may be missed by techniques other than color Doppler echocardiography. The striking findings on color Doppler may help to make this important diagnosis in such patients.


Effect of cisplatin on calcium uptake by rat kidney cortical mitochondria.
The effect of the nephrotoxic antineoplastic drug, cisplatin, on mitochondrial calcium uptake was examined in rat kidney cortical mitochondria. We treated rats with cisplatin (5 mg/kg, i.p.), and prepared and incubated the mitochondria. Uptake of calcium decreased after 24 h. The mitochondria contained platinum even 3 days after injection. Cisplatin (0.5 mM) added to incubation medium inhibited calcium uptake. Platinum accumulated in the mitochondria during incubation. Mitochondria accumulated less of another divalent cation, magnesium, in rats given cisplatin and in incubation medium with cisplatin added. The results suggest that cisplatin taken up into kidney cortical mitochondria inhibited divalent cation uptake there, which may contribute to cisplatin nephrotoxicity.


Genetic characterization of Microcystis aeruginosa isolates from Portuguese freshwater systems.
Cyanobacteria are microorganisms that pose a serious threat to the aquatic waterways through the production of dense blooms under eutrophic conditions and the release of toxic secondary metabolites-cyanotoxins. Within cyanobacteria, the colonial planktonic Microcystis aeruginosa is widely distributed in both fresh and brackish aquatic environments throughout the world being frequently observed in the Portuguese water systems. Apart from the well-established distribution of M. aeruginosa in Portugal, knowledge of its genetic diversity and population structure is unknown. Therefore, in this study twenty-seven strains were obtained from the North, Centre and South regions of Portugal and were subjected to extensive phylogenetic analyses using simultaneously four distinct genetic markers (16S rRNA, 16S-23S ITS, DNA gyrase subunit ß and cell division protein (ftsZ)) encompassing in total 2834 bp. With this work we characterized the phylogenetic relationship among the Portuguese strains, with the southern strains showing higher genetic structure relatively to the North and Centre strains. A total of fifteen genotypes were determined for M. aeruginosa in Portuguese water systems revealing a high genetic diversity. This is also the first study to report geographic variation on the population structure of the Portuguese M. aeruginosa.


Epithelial maturation and extracellular matrix in reduced enamel epithelium.
To evaluate epithelial-mesenchymal interactions in morphological homeostasis through histologically orientated observations on the reduced enamel in epithelium. Specimens were taken from impacted molar sites in 20 patients using the surgery. These were processed using standard histological, pathological and biochemical techniques. Slides were observed with a Nikon Eclipse E-600, Plan Apo piece, Microscopy, and photography was done using a Nikon Coolpix 990 digital camera. Radiolucent lesions displayed the supporting fibrous connective tissue wall with stratified squamous epithelium lining mostly. None of the specimens displayed prominent CAM 5.2, and anti-human K7 reacuvity, and PAS positive staining. While the results of this study suggest that the reduced enamel epithelium showed a lower tendency in cell cycle, it does indicate that a histologically oriented study of reduced enamel epithelium is needed for the understanding of epithelial-mesenchymal interactions in morphogenesis.


SynBioStrainFinder: A microbial strain database of manually curated CRISPR/Cas genetic manipulation system information for biomanufacturing.
Microbial strain information databases provide valuable data for microbial basic research and applications. However, they rarely contain information on the genetic operating system of microbial strains. We established a comprehensive microbial strain database, SynBioStrainFinder, by integrating CRISPR/Cas gene-editing system information with cultivation methods, genome sequence data, and compound-related information. It is presented through three modules, Strain2Gms/PredStrain2Gms, Strain2BasicInfo, and Strain2Compd, which combine to form a rapid strain information query system conveniently curated, integrated, and accessible on a single platform. To date, 1426 CRISPR/Cas gene-editing records of 157 microbial strains have been manually extracted from the literature in the Strain2Gms module. For strains without established CRISPR/Cas systems, the PredStrain2Gms module recommends the system of the most closely related strain as a reference to facilitate the construction of a new CRISPR/Cas gene-editing system. The database contains 139,499 records of strain cultivation and genome sequences, and 773,298 records of strain-related compounds. To facilitate simple and intuitive data application, all microbial strains are also labeled with stars based on the order and availability of strain information. SynBioStrainFinder provides a user-friendly interface for querying, browsing, and visualizing detailed information on microbial strains, and it is publicly available at http://design.rxnfinder.org/biosynstrain/ . SynBioStrainFinder is the first microbial strain database with manually curated information on the strain CRISPR/Cas system as well as other microbial strain information. It also provides reference information for the construction of new CRISPR/Cas systems. SynBioStrainFinder will serve as a useful resource to extend microbial strain research and application for biomanufacturing.


Mental health literacy levels.
Globally, mental disorders affect 25% of the society. This discursive paper aims to illustrate the mental health literacy levels in the public. Mental health literacy (MHL) is the understanding of mental health conditions, which helps in their prevention, recognition and treatment. Unfortunately, the public has minimal understanding of mental disorders, leading to poor recognition and delay in treatment. There is a need to conduct good quality research to assess the MHL levels among public and tailor interventions to enhance MHL among the public. This will ensure early detection of mental disorders, leading to early recovery and greater quality of life among the society. Nurses have a great role to play in leading these public educations, and enhancing a healthy and happy nation.


LPS-induced production of TNF-α and IL-6 in mast cells is dependent on p38 but independent of TTP.
The production of the proinflammatory cytokines TNF-α and IL-6 is regulated by various mRNA-binding proteins, influencing stability and translation of the respective transcripts. Research in macrophages has shown the importance of the p38-MK2-tristetraprolin (TTP) axis for regulation of TNF-α mRNA stability and translation. In the current study we examined a possible involvement of p38 and TTP in LPS-induced cytokine production in bone marrow-derived mast cells (BMMCs). Using pharmacological inhibitors we initially found a strong dependence of LPS-induced TNF-α and IL-6 production on p38 activation, whereas activation of the Erk pathway appeared dispensable. LPS treatment also induced p38-dependent expression of the TTP gene. This prompted us to analyze the proinflammatory cytokine response in BMMCs generated from TTP-deficient mice. Unexpectedly, there were no significant differences in cytokine production between TTP-deficient and WT BMMCs in response to LPS. Gene expression and cytokine production of TNF-α and IL-6 as well as stability of the TNF-α transcript were comparable between TTP-deficient and WT BMMCs. In contrast to TTP mRNA expression, TTP protein expression could not be detected in BMMCs. While we successfully precipitated and detected TTP from lysates of LPS-stimulated RAW 264.7 macrophages, this was not accomplished from BMMC lysates. In contrast, we found mRNA and protein expressions of the other TIS11 family members connected to regulation of mRNA stability, BRF1 and BRF2, and detected their interaction with 14-3-3 proteins. These data suggest that control of cytokine mRNA stability and translation in MCs is exerted by proteins different from TTP.


Update meta-analysis on the efficacy and safety issues of fexofenadine.
Fexofenadine emerged as one of the most representative second generation histamine H1 antagonist drugs since the 1990s, with an outstanding efficacy and appreciable safety for the treatment of allergic patients. While allergic rhino-conjunctivitis represents the most frequent atopic disease globally, an update of fexofenadine efficacy and safety on this entity was proposed as a surrogate of allergic condition. Double blind, placebo controlled, randomized clinical trials investigating the efficacy and safety of fexofenadine for the treatment of Allergic Rhinitis were searched in 5 major global databases. Eligibility criteria and characteristics, risk of bias, and validity assessment, data extraction and heterogeneity evaluation are described. Primary outcome selected corresponded to 12-reflective and instantaneous total symptom scores (TSS), besides morning instantaneous TSS and the frequency of reported adverse events (AEs); analysis was planned on the intention-to-treat population.Standardized mean differences of scoring systems were analyzed, and Cochran's Q statistic test and the I2 test were assessed for heterogeneity. From the initial 83 identified records, 12 eligible studies were selected. In the evaluated patients, individuals receiving fexofenadine (1910) showed a significant reduction of TSS compared with those who received placebo (1777), change from baseline: standardized mean difference (SMD) -0.33; 95% CI-0.47 to -0.18, p < 0.0001. Morning instantaneous TSS also demonstrated lower symptoms (change from baseline: SMS -1.42; 95% CI -2.22 to -0.62, p = 0.0005). Heterogeneity was found across selected studies.Frequency of AEs was similar compared to placebo (OR = 1.04; 0.88-1.21), with no detection of heterogeneity across these 12 studies. According to this new evidence, fexofenadine maintains its beneficial profile on signs and symptoms of patients with allergic conditions, as well as its attributes as one of the major candidates for an ideal antihistamine medication (including special conditions such as pregnancy and pre-school age), providing support to its over-the-counter condition in several countries.


An improved method for single cell isolation of prokaryotes from meso-, thermo- and hyperthermophilic environments using micromanipulation.
This study presents an improved system that enables isolation of single viable prokaryotic cells from a mixture of cells. The system is based on an inverted microscope, a microinjector and a micromanipulator. The isolated cell is captured in a microcapillary from a volume of 400 mul and transferred to an appropriate growth medium. Validation of the system was performed using two fluorescent strains: Pseudomonas putida expressing red fluorescent protein (DsRed), and Escherichia coli expressing green fluorescent protein (GFP). A mixture (100:1) of the constructed fluorescent strains was subjected to isolation experiments and nine out of ten individually isolated cells yielded axenic cultures of E. coli. Upon construction and validation, the system was used to isolate and subsequently cultivate axenic cultures of the thermophilic Archaeon Metallosphaera sedula and the hyperthermophilic Archaeon Sulfolobus solfataricus from enriched hot spring samples. The high efficiency of single-cell isolation and cultivation demonstrated over a range of temperatures-90% (30 degrees C), 85% (70 degrees C) and 95% (80 degrees C)-from different environments is probably due to the elimination of osmotic stress and limitation of temperature fluctuations during the isolation process, as a result of the large sample volume from which the cells are isolated.


Reduced startle gating after D1 blockade: effects of concurrent D2 blockade.
Prefrontal D1 systems have been implicated in the regulation of working memory and in the pathophysiology of schizophrenia. D1 hypofunction might contribute to reduced sensorimotor gating in schizophrenia patients since D1 activity in the medial prefrontal cortex (MPFC) regulates prepulse inhibition of startle (PPI) in animal models. We studied the neurochemical basis for the D1 regulation of PPI in rats. PPI to weak (1-5 dB over background) prepulses was measured after systemic or intra-MPFC administration of the D1 antagonist, SCH 23390, in rats pretreated systemically with the D2 antagonist, haloperidol (vehicle or 0.1 mg/kg). After vehicle pretreatment, systemic and intra-MPFC SCH 23390 disrupted PPI produced by weak prepulses. This effect was not significantly opposed by pretreatment with haloperidol (0.1 mg/kg). In contrast, the PPI-disruptive effects of the DA agonist amphetamine were significantly opposed by this dose of haloperidol. D1 blockade reduces PPI, but this effect does not appear to be mediated entirely via increased dopamine transmission at D2 receptors.


Hb S-São Paulo: a new sickling hemoglobin with stable polymers and decreased oxygen affinity.
Hb S-São Paulo (SP) [HBB:c.20A>T p.Glu6Val; c.196A>G p.Lys65Glu] is a new double-mutant hemoglobin that was found in heterozygosis in an 18-month-old Brazilian male with moderate anemia. It behaves like Hb S in acid electrophoresis, isoelectric focusing and solubility testing but shows different behavior in alkaline electrophoresis, cation-exchange HPLC and RP-HPLC. The variant is slightly unstable, showed reduced oxygen affinity and also appeared to form polymers more stable than the Hb S. Molecular dynamics simulation suggests that the polymerization is favored by interfacial electrostatic interactions. This provides a plausible explanation for some of the reported experimental observations.


Development of a capillary electrophoresis method for the determination of orphenadrine citrate in tablets in the presence of paracetamol.
A validated method using capillary electrophoresis was developed, for the determination of orphenadrine citrate in its tablet formulations, in the presence of paracetamol. The method employs a running buffer of 30 mM pentane sulfonate sodium, dissolved in 20 mM MOPS buffer pH 7.7. Samples were injected using hydrodynamic sample injection mode (25 mbar, for 25 s), using positive polarity of 25 kV, at a constant temperature of 30 °C. Samples of orphenadrine citrate alone or in mixture solutions with paracetamol were exposed to various degradation conditions, and were electrophoresed using the recommended condition. The method was found to be specific, linear (r (2) = 0.994), precise, accurate, and robust, with an LOQ of 0.02 mg/mL. The proposed method was successfully applied for measurement of the percentage per label of orphenadrine citrate in commercially available tablets.


The effect of the lattice spacing change on cross-bridge kinetics in chemically skinned rabbit psoas muscle fibers. II. Elementary steps affected by the spacing change.
The actin-myosin lattice spacing of rabbit psoas fibers was osmotically compressed with a dextran T-500, and its effect on the elementary steps of the cross-bridge cycle was investigated. Experiments were performed at the saturating Ca (pCa 4.5-4.9), 200 mM ionic strength, pH 7.0, and at 20 degrees C, and the results were analyzed by the following cross-bridge scheme: [formula: see text] where A = actin, M = myosin head, S = MgATP, D = MgADP, and P = Pi = phosphate. From MgATP and MgADP studies on exponential process (C) and (D), the association constants of cross-bridges to MgADP (K0), MgATP (K1a), the rate constants of the isomerization of the AM S state (k1b and k-1b), and the rate constants of the cross-bridge detachment step (k2 and k-2) were deduced. From Pi study on process (B), the rate constants of the cross-bridge attachment (power stroke) step (k4- and k-4) and the association constant of Pi ions to cross-bridges (K5) were deduced. From ATP hydrolysis measurement, the rate constant of ADP-isomerization (rate-limiting) step (k6) was deduced. These kinetic constants were studied as functions of dextran concentrations. Our results show that nucleotide binding, the ATP-isomerization, and the cross-bridge detachment steps are minimally affected by the compression. The rate constant of the reverse power stroke step (k-4) decreases with mild compression (0-6.3% dextran), presumably because of the stabilization of the attached cross-bridges in the AM*DP state. The rate constant of the power stroke step (k4) does not change with mild compression, but it decreases with higher compression (> 6.3% dextran), presumably because of an increased difficulty in performing the power stroke. These results are consistent with the observation that isometric tension increases with a low level of compression and decreases with a high level of compression. Our results also show that the association constant K5 of Pi with cross-bridge state AM*D is not changed with compression. Our result further show that the ATP hydrolysis rate decreased with compression, and that the rate constants of the ADP-isomerization step (k6) becomes progressively less with compression. The effect of compression on the power stroke step and rate-limiting step implies that a large-scale molecular rearrangement in the myosin head takes place in these two slow reaction steps.


Antithyroid and antiperoxidase activity of tropolone and 3-hydroxy-4-pyrone.
Tropolone (TR) and 3-hydroxy-4-pyrone were investigated for antithyroid activity following the finding that the 2-hydroxy-oxo pyridine, 3-hydroxy-4(1H)-pyridone (DHP, I), is goitrogenic. Both compounds inhibited the thyroidal uptake of radioiodine in rats and resembled the thioamide drugs in inhibiting the organic binding of iodine by the thyroid gland rather than the trapping of iodide, but were weaker binding inhibitors than 6-methyl-2-thiouracil (MeTU). Both compounds also inhibited the iodination of bovine serum albumin and thyroglobulin, catalyzed by thyroidperoxidase (TPO), lactoperoxidase (LPO), chloroperoxidase (CPO) and horseradish peroxidase (HPO) in vitro. The inhibitory effect of TR but not that of 3-hydroxy-4-pyrone was antagonized by ferrous ions. When fed to mice at levels of intake expected to produce goitre both compounds were toxic and caused severe liver damage. Thyroid enlargement was not observed in any of these feeiding experiments, but the thyroids of mice fed 0.1% TR showed moderate hyperplasia. It was concluded that both compounds are weakly goitrogenic. Hyperactivity was observed in the mice fed TR which may be associated with inhibition of catechol methyl transferase (COMT).


Regulation of male fertility by the endocannabinoid system.
Mammalian conception is a complex process regulated by both sexual behavior and reproductive performance. Alcohol, marijuana and tobacco are among the main factors which affect negatively fertility in women and men. Several studies have demonstrated that marijuana impairs the male copulatory activity, and that smokers of this illegal drug show reduced fertility due, for instance, to decrease in sperm concentration, defective sperm function or alteration of sperm morphology. The discovery of endocannabinoids and all components responsible for their metabolism has allowed to collect valuable information on the effects of these endogenous lipids, able to mimic the actions of delta-9-tetrahydrocannabinol (THC), in reproductive functions. The purpose of this review is to describe the actions of cannabinoids and endocannabinoids on the control of procreation and hormonal release during the fertilization process in males.


Alterations in synaptic density and myelination in response to exposure to high-energy charged particles.
High-energy charged particles are considered particularly hazardous components of the space radiation environment. Such particles include fully ionized energetic nuclei of helium, silicon, and oxygen, among others. Exposure to charged particles causes reactive oxygen species production, which has been shown to result in neuronal dysfunction and myelin degeneration. Here we demonstrate that mice exposed to high-energy charged particles exhibited alterations in dendritic spine density in the hippocampus, with a significant decrease of thin spines in mice exposed to helium, oxygen, and silicon, compared to sham-irradiated controls. Electron microscopy confirmed these findings and revealed a significant decrease in overall synapse density and in nonperforated synapse density, with helium and silicon exhibiting more detrimental effects than oxygen. Degeneration of myelin was also evident in exposed mice with significant changes in the percentage of myelinated axons and g-ratios. Our data demonstrate that exposure to all types of high-energy charged particles have a detrimental effect, with helium and silicon having more synaptotoxic effects than oxygen. These results have important implications for the integrity of the central nervous system and the cognitive health of astronauts after prolonged periods of space exploration.


Precision aiming performance with the paretic upper limb is associated with center of pressure patterns in individuals with chronic stroke.
Individuals with stroke commonly demonstrate upper-limb sensorimotor impairments. Upper-limb tasks occur against a background level of postural control and thus require a flexible postural control system to facilitate performance. Anterior precision aiming tasks, for example, benefit from lower medial-lateral (ML) center of pressure (COP) fluctuations (where increased fluctuations erode performance) relative to anterior-posterior (AP) fluctuations (where increased fluctuations do not strongly influence performance). After stroke, individuals may compensate for upper-limb impairments by increasing trunk movement which increases overall COP fluctuations and thus may make it more difficult to modulate COP in a task-sensitive manner. Do upper-limb task demands modulate COP movement patterns after stroke? In this cross-sectional study, adults with chronic stroke (n = 23) and unilateral upper-limb impairments were immersed in a virtual environment displaying an anterior target. Participants aimed to maintain the position of a virtual laser pointer (via handheld controller) in the target with each hand. COP was concurrently recorded. Mixed effects models and correlations were used to detect differences in COP patterns between limbs and movement planes and evaluate associations between task performance and COP patterns, respectively. Participants showed greater COP standard deviation and regularity in the AP compared to the ML direction. The magnitude of difference between AP and ML COP metrics was greater using the nonparetic limb. Task performance was moderately and positively associated with task-sensitive COP patterns (i.e., higher AP:ML ratios of COP metrics) using the paretic upper limb. Participants consistently demonstrated high levels of task performance and task-sensitive COP movement patterns using the nonparetic limb. Impairments in postural control after stroke may be related to the upper limb used. It is important to recognize the role of directional COP variability and regularity in the context of a task goal after stroke.


Chemiluminescence-based electrophoretic mobility shift assay of RNA-protein interactions: application to binding of viral capsid proteins to RNA.
A chemiluminescence electrophoretic mobility shift assay was introduced for the study of RNA-protein interactions that include association of genomic RNA and viral capsid proteins. Binding of the capsid protein of Venezuelan equine encephalitis virus (VEEV) to several types of RNA was used as a model system to test the application of the method. The effects of RNA secondary structures and the significance of electrostatic interaction on binding were identified. This method may have wide application to the study of RNA-protein interactions.


Identification of a novel broad-spectrum endolysin, Ply0643, with high antibacterial activity in mouse models of streptococcal bacteriaemia and mastitis.
Streptococcal infections are very common in humans and animals, and they are usually treated with antibiotics. Multidrug-resistant Streptococcus strains have continuously emerged in recent years, prompting the search for alternatives to antibiotics. The use of endolysins encoded by phages has presented a promising alternative approach to treatment. In this study, a novel prophage endolysin, Ply0643, was identified from the prophage S. a 04. At an optimal concentration (30 μg/mL), rPly0643 exhibited broad and strong lysosomal enzyme activity against 66 Streptococcus strains from different sources while also maintaining high lytic activity over a wide pH range (pH 6-10) and a broad range of temperatures (28 °C-45 °C). Two in vivo treatments of rPly0643 (total 0.8 mg/mouse) significantly protected mice (80%) from lethal bacteriaemia with Streptococcus suis, and single treatments of rPly0643 (0.1 mg/gland) significantly reduced Streptococcus agalactiae concentrations and inflammation in murine mammary glands. These findings collectively demonstrate that Ply0643 exhibits good bactericidal activity both in vitro and in vivo, and therefore represents a useful antibacterial agent for combatting streptococcal infections.


Metabolic dissimilarity determines the establishment of cross-feeding interactions in bacteria.
The exchange of metabolites among different bacterial genotypes profoundly impacts the structure and function of microbial communities. However, the factors governing the establishment of these cross-feeding interactions remain poorly understood. While shared physiological features may facilitate interactions among more closely related individuals, a lower relatedness should reduce competition and thus increase the potential for synergistic interactions. Here, we investigate how the relationship between a metabolite donor and recipient affects the propensity of strains to engage in unidirectional cross-feeding interactions. For this, we performed pairwise cocultivation experiments between four auxotrophic recipients and 25 species of potential amino acid donors. Auxotrophic recipients grew in the vast majority of pairs tested (63%), suggesting metabolic cross-feeding interactions are readily established. Strikingly, both the phylogenetic distance between donor and recipient and the dissimilarity of their metabolic networks were positively associated with the growth of auxotrophic recipients. Analyzing the co-growth of species from a gut microbial community in silico also revealed that recipient genotypes benefitted more from interacting with metabolically dissimilar partners, thus corroborating the empirical results. Together, our work identifies the metabolic dissimilarity between bacterial genotypes as a key factor determining the establishment of metabolic cross-feeding interactions in microbial communities.


Comparisons of prognostic factors between young and elderly patients with chronic heart failure.
The purpose in the present study was to compare prognostic risk factors between older and younger chronic heart failure (CHF) patients. We examined 598 consecutive CHF patients (476 men and 122 women, mean age 61.4 ± 14.3 years) who underwent cardiopulmonary exercise testing, echocardiography and blood examination. We divided the 598 patients into two groups: the elderly group (age ≥75 years, n = 123) and the young group (age <75, n = 475). We compared blood testing data, exercise capacity, cardiac function and prognosis between the two groups. Patients were followed up (median 782 days) to register cardiac deaths or rehospitalization as a result of worsening heart failure. Patients in the elderly group were associated with higher frequencies of atrial fibrillation and diuretic use than those in the young group. Patients in the elderly group had lower hemoglobin concentration, more impaired renal function, higher plasma B-type natriuretic peptide (BNP) levels, smaller left ventricular volume, longer deceleration time of early mitral wave and lower exercise capacity than those in the young group. There were 199 cardiac events during follow-up periods. As expected, Kaplan-Meier analysis showed that patients in the elderly group had higher cardiac event rates than those in the young group. In the young group, multivariable Cox hazard analysis showed that hemoglobin concentration, log BNP and peak VO(2) were independent predictors related to cardiac events. In contrast, in the elderly group, estimated glomerular filtration rate, atrial fibrillation and peak VO(2) were independent factors to predict adverse clinical outcomes. Prognostic factors were different between the elderly and young patients in CHF.


Simultaneous occurrence of foetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies: a case study and review of the literature.
Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia caused by maternal autoantibodies against HNA-1b. This appears to be the first case of simultaneous occurrence of these two conditions. This case report and review of the literature demonstrate that anti-HPA-3a antibodies can be overlooked by standard assays.


Facial trauma and ocular/orbital injury.
Ocular injuries occur commonly in patients with facial trauma. Patients with significant eye injuries may present with grossly normal eyes and good visual acuity; however, subsequent ocular disorders may become apparent. The estimates of incidence vary considerably. Trauma is the second leading cause of blindness, and a review is, therefore, warranted. Several extensive studies are reviewed. Blunt and penetrating trauma are examined by their respective subdivisions. The initial assessment and ophthalmologic examination of patients with facial trauma are discussed, and the type of injury that may occur secondary to trauma is delineated. Management is reviewed and discussed, including a recently developed diagnostic scoring system. Three clinical cases illustrate the procedure. The diagnosis of ocular injuries resulting from trauma is difficult. The recently introduced scoring system was found to improve the procedure. Based on this system, the authors have devised an algorithm to assist the clinician, with emphasis on visual acuity and the importance of visual examination.