Immunoglobulin G galactosylation levels are decreased in systemic sclerosis patients and differ according to disease subclassification.
Objectives: Scleroderma is a connective tissue immune disease that features collagen overproduction and can be categorized into two subtypes, localized scleroderma (LSc) and systemic sclerosis (SSc). SSc is clinically classified into two subsets: limited cutaneous (lcSSc) and diffuse cutaneous (dcSSc) SSc. The immunoglobulin G-galactosylation (IgG-Gal) ratio is abnormal in a number of immune diseases and has not been evaluated in SSc.Method: The study recruited 93 LSc patients, 298 SSc patients, and 436 healthy controls. N-glycans of purified IgG were obtained from plasma and detected by tandem mass spectrometry. The IgG-Gal ratio was measured by calculating the relative intensities of agalactosylated (G0), monogalactosyl (G1), and digalactosyl (G2) N-glycans according to the formula G0/(G1 + G2 × 2). Furthermore, we examined whether the IgG-Gal ratio differed between different subtypes of SSc.Results: The IgG-Gal ratio was significantly higher in SSc patients (1.139 ± 0.870) than in LSc patients (0.485 ± 0.280) and controls (0.395 ± 0.190). The IgG-Gal ratio successfully distinguished SSc patients from LSc and controls (area under the curve = 0.88 and 0.81, respectively). The IgG-Gal ratio was significantly higher in dcSSc patients than in lcSSc patients and increased along with increases in modified Rodnan skin score (p = 6.03 × 10-5, Pearson's coefficient = 0.26) and erythrocyte sedimentation rate (p = 2.95 × 10-10, Pearson's coefficient = 0.38).Conclusion: IgG-Gal ratios were abnormal in SSc patients and were associated with disease severity. The IgG-Gal ratio therefore shows potential as a biomarker for the diagnosis of SSc.


Physiological comparison of three spontaneous breathing trials in difficult-to-wean patients.
To compare cardiovascular and respiratory responses to different spontaneous breathing trials (SBT) in difficult-to-wean patients using T-piece and pressure support ventilation (PSV) with or without positive end-expiratory pressure (PEEP). Prospective physiological study. Fourteen patients who were monitored with a Swan-Ganz catheter and had failed a previous T-piece trial were studied. Three SBTs were performed in random order in all patients: PSV with PEEP (PSV-PEEP), PSV without PEEP (PSV-ZEEP), and T-piece. PSV level was 7 cmH(2)O, and PEEP was 5 cmH(2)O. Inspiratory muscle effort was calculated, and hemodynamic parameters were measured using standard methods. RESULTS [MEDIAN (AND INTERQUARTILE RANGE)]: Most patients succeeded in the PSV-PEEP (11/14) and PSV-ZEEP (8/14) trials, but all failed the T-piece trial. Patient effort was significantly higher during T-piece than during PSV with or without PEEP [esophageal pressure-time product was 292 (238-512), 128 (58-299), and 148 (100-465) cmH(2)O x s/min, respectively, p < 0.05]. Left ventricular heart failure was observed in 11 of the 14 patients during the T-piece trial. Pulmonary artery occlusion pressure and respiratory rate were significantly higher during T-piece than with PSV-PEEP [21 (18-24) mmHg versus 17 (14-22) mmHg, p < 0.05 and 27 (21-35) breaths/min versus 19 (16-29) breaths/min, p < 0.05 respectively]. Tidal volume was significantly lower during the T-piece trial. In this selected population of difficult-to-wean patients, PSV and PSV plus PEEP markedly modified the breathing pattern, inspiratory muscle effort, and cardiovascular response as compared to the T-piece. Caregivers should be aware of these differences in SBT as they may play an important role in weaning decision-making.


Correction: Oleuropein down-regulated IL-1β-induced inflammation and oxidative stress in human synovial fibroblast cell line SW982.
Correction for 'Oleuropein down-regulated IL-1β-induced inflammation and oxidative stress in human synovial fibroblast cell line SW982' by Maria Luisa Castejón, et al., Food Funct., 2017, DOI: 10.1039/c7fo00210f.


Effect of nitrogen deficiency on the stability of aerobic granular sludge.
To assess the stability of aerobic granular sludge (AGS) under nitrogen deficiency conditions, three sequence batch reactors were operated with chemical oxygen demand (COD) to nitrogen (N) ratios of 100/5, 100/2.5, and 100/2, while COD concentration was kept consistent. AGS variations in its physicochemical characteristics, microbial community, and treatment performance were investigated. The results indicated that good treatment performance and stable AGS were achieved under nitrogen deficiency. Extracellular polymeric substances (EPS) regulating mechanism preserved AGS stability under nitrogen deficiency, especially through increased secretion of polysaccharide. In addition, members of the Anaerolineaceae were the major filamentous bacteria, which are strictly anaerobic organism, providing a possible explanation to the lack of filamentous bacteria outgrowth under N deficient condition. Insights from this study could help lower chemical costs in AGS applications for specific industrial wastewater treatments.


Psychometric properties of Brief-Balance Evaluation Systems Test (Brief-BESTest) in evaluating balance performance in individuals with chronic stroke.
To examine the psychometric properties of the Brief-Balance Evaluation Systems Test (Brief-BESTest) in individuals with chronic stroke. This was an observational study with repeated measurements involving 50 participants with chronic stroke [mean (SD) age: 59.2 (7.3) years]. Each participant with stroke was evaluated with the Brief-BESTest, Berg balance scale (BBS), Postural Assessment Scale for Stroke Patients (PASS), Fugl-Meyer Motor Assessment (FMA), Chedoke-McMaster Stroke Assessment (CMSA), Montreal Cognitive Assessment (MoCA), and Geriatric Depression Scale (GDS). Two raters (rater 1 and 2) provided the Brief-BESTest scores of the first 27 participants independently to establish inter-rater reliability. After 15 min of rest, the same 27 participants were evaluated with the Brief-BESTest again by rater 1 to establish intra-rater reliability. The Brief-BESTest scores of the stroke group were also compared with those of the control group [n = 27, mean (SD) age: 56.7 (7.7) years]. The Brief-BESTest had no substantial floor and ceiling effects, good intra-rater (ICC 2,1 = 0.974) and inter-rater (ICC 2,1 = 0.980) reliability and internal consistency (Cronbach's alpha = 0.818). The minimal detectable change at 95% confidence level was 2 points. The Brief-BESTest showed moderate to very strong correlations with other balance (BBS and PASS) and motor impairment (FMA, CMSA) measures (rs = .547-.911, p < .001), thus revealing good concurrent and convergent validity. Its correlation with measures that evaluated other constructs was weaker (MoCA: rs = .437, p = .002) or non-significant (GDS: rs = -0.152, p = .292), thus showing good discriminant validity. Good known-groups validity was established, as the Brief-BESTest was effective in distinguishing participants with stroke from controls (cutoff score: <18, area under curve: 0.942), and individuals with stroke who required assistive device for their outdoor mobility from those who did not (cutoff score <14, area under curve: 0.810). The Brief-BESTest has good reliability and validity in assessing balance function in individuals with chronic stroke.


ASSESSMENT OF CARDIOVASCULAR RISK IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND ASSOCIATED OBESITY AND WAYS OF ITS CORRECTION.
The aim: To analyze and calculate CVR in patients with T2DM and concomitant obesity. Materials and methods: The selection of patients was carried out based on the Uzhhorod District Clinical Hospital, in the period from November 2016 to January 2020. All patients were divided into 3 groups: 1 (n=93) with T2DM and concomitant obesity, 2 (n=87) with T2DM, 3 (n=39) with obesity. The treatment period lasted 1 year and included dosed exercise for at least 30 minutes per day and dietary recommendations. Patients in groups 1 and 2 received metformin 850 mg twice daily in combination with dapagliflozin 10 mg once daily. CVR was determined at the time of enrollment and after 1 year of treatment using: American College of Cardiology / American Heart Association Guideline on the Assessment of Cardiovascular Risk (2013) (ASCVD Risk) and Framingham Risk Score (FRS). Results: The data obtained as a result of the study revealed the highest CVR in patients of group 1, in contrast to group 2 and 3 (p<0.05). After 1 year of complex treatment, CVR indicators were statistically significantly reduced in all experimental groups (p<0.05). Conclusions: Determining CVR parameters and exposure to them within 10 years can remove unwanted cardiovascular complications.


Cold versus hot polypectomy/endoscopic mucosal resection-A review of current evidence.
Colonoscopy with polypectomy substantially reduces the risk of colorectal cancer (CRC) but interval cancers still account for 9% of all CRCs, some of which are due to incomplete resection. The aim of this review is to compare the outcomes of cold and hot endoscopic resection and provide technical tips and tricks for optimizing cold snare polypectomy. Cold snare polypectomy (CSP) is the standard technique for small (≤10 mm) colorectal polyps. For large colonic polyps (>10 mm), hot resection techniques with use of electrocautery (polypectomy or endoscopic mucosal resection) were recommended until recently. However, the use of electrocoagulation brings serious adverse effects in up to 9% of the patients, such as delayed bleeding, post-polypectomy syndrome and perforation. In recent years, efforts have been made to improve the polypectomy with cold snare in order to avoid these adverse effects of electrocoagulation without compromising the efficacy of the resection. Several authors have recently shown that the complication rates of CSP of polyps >10 mm is close to zero and recurrence rates varies between 5-18%. Lower recurrence rates are found in serrated lesions (<8%).


The association between the Kessler 10 and suicidality: a cross-sectional analysis.
The aims of this study were to test the psychometric properties of the Kessler 10 (K10) in a clinical setting and to investigate the utility of the K10 as a means for identifying suicidality. One hundred forty-nine inpatients at an inpatient psychiatric hospital completed a battery of assessments during their inpatient hospital stay. Factor analysis provided information suggesting multiple factor loadings present within the K10. A series of t tests examined differences of group means between suicidal participants and a control group, whereas multiple regression models examined the correlation between the K10 and several suicide-specific assessments. The K10 seems to be composed of 2 primary factors (depression and anxiety) and differentiated suicidal and nonsuicidal inpatients and was associated with several measures related to suicidality. The observed results indicate that the K10 may be an effective screener to measure occult suicidality in a clinical setting.


Prevalence and patterns of cigarette smoking before and during early and late pregnancy according to maternal characteristics: the first national data based on the 2003 birth certificate revision, United States, 2016.
The objective of this study was to examine the prevalence of smoking by intensity status before pregnancy and during early (first and second trimester) and late (third trimester) pregnancy according to race/ethnicity, age, and educational attainment of women who gave birth in the United States in 2016. This cross-sectional study was based on the 2016 National Center for Health Statistics (NCHS) Natality File of 3,956,112 live births, the first year that it became 100% nationally representative. Self-reported smoking data were used to create new seven smoking intensity status categories to capture natural variability in smoking patterns during pregnancy and to identify maternal smokers by race/ethnicity, age, and educational attainment. The risk of smoking at low and high intensity in early pregnancy was estimated in multivariable logistic regression analyses. Nearly 9.4% of women reported smoking before pregnancy and 7.1% during pregnancy, both at high and low intensity, and smoking rates were higher in the first trimester (7.1%) than in the second (6.1%) or the third (5.7%) trimester. Non-Hispanic White women, women 20-24 years old, and women with less than a high school education were the strongest predictors of smoking anytime during pregnancy. The odds of smoking in early pregnancy at high intensity were 88% lower (aOR 0.12, 95% CI: 0.11, 0.13) for Hispanic women, compared to non-Hispanic White women; 16% higher (aOR 1.16, 95% CI: 1.12, 1.21) for women 20-24 years old and 16% lower (aOR 0.84, 95% CI: 0.80, 0.89) for women ≥35 years old, compared to women 25-29 years old; as well as 13% higher (aOR 1.13, 95% CI: 1.09, 1.18) for women with less than a high school education and 92% lower (aOR 0.08, 95% CI: 0.08, 0.09) for women with a bachelor's degree or higher, compared to women with a high school diploma. Despite the high prevalence of high intensity smoking before and during pregnancy, future intervention strategies need to focus on the proportion of low intensity quitters and reducers, who are ready to stop smoking. Continual monitoring of trends in smoking intensity patterns is necessary, including neonatal outcomes over time.


Cohort study evaluation of New Chinese Diabetes Risk Score: A new non-invasive indicator for predicting metabolic syndrome.
To investigate the association of the baseline New Chinese Diabetes Risk Score (NCDRS) with metabolic syndrome (MetS) risk and to evaluate the power of the baseline NCDRS to predict MetS based on the rural Chinese cohort study. Study participants were classified by baseline quartiles of NCDRS by gender. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of MetS according to different diagnostic criteria. The receiver operating characteristic curve (ROC) and area under the ROC curve (AUC) were used to evaluate the power of the baseline NCDRS for predicting MetS according to different diagnostic criteria. We included 7,133 participants, and 1,651 MetS cases were identified after 6 years follow-up. After adjusting for multivariable confounding factors and with NCDRS quartile 1 as the reference, with quartile 4, the risk of MetS was increased for all participants, men and women: ORs (95% CIs) 4.03 (3.23-5.02), 3.59 (2.56-5.05) and 5.71 (4.23-7.70), respectively. Similar results were found on sensitivity analysis. The baseline NCDRS was a good predictor of MetS for all participants, men and women with MetS defined according to the diagnostic criteria of the Chinese Joint Committee on the Development of Guidelines for the Prevention and Treatment of Dyslipidemia in Adults (JCDCG). Our study, based on the cohort study, found that the baseline NCDRS was positively associated with risk of MetS. Furthermore, our study might provide suggestions for developing a useful and inexpensive tool for predicting MetS in the Chinese population.


Lactic acid production by mixed cultures of Kluyveromyces marxianus, Lactobacillus delbrueckii ssp. bulgaricus and Lactobacillus helveticus.
Lactic acid production using Kluyveromyces marxianus (IFO 288), Lactobacillus delbrueckii ssp. bulgaricus (ATCC 11842) and Lactobacillus helveticus (ATCC 15009) individually or as mixed culture on cheese whey in stirred or static fermentation conditions was evaluated. Lactic acid production, residual sugar and cell biomass were the main features examined. Increased lactic acid production was observed, when mixed cultures were used in comparison to individual ones. The highest lactic acid concentrations were achieved when K. marxianus yeast was combined with L. delbrueckii ssp. bulgaricus, and when all the strains were used revealing possible synergistic effects between the yeast and the two lactic acid bacteria. The same synergistic effects were further observed and verified when the mixed cultures were applied in sourdough fermentations, proving that the above microbiological system could be applied in the food fermentations where high lactic acid production is sought.


Growth Performance, Biochemical Blood Indices, and Large Intestine Physiology of Rats Fed Diets with Alfalfa Protein-Xanthophyll Concentrate.
The effect of dietary levels of alfalfa protein-xanthophyll concentrate (PXC) was determined in growing rats. Three groups of eight four-week-old male Wistar rats, with an average initial body weight of 61 g, were fed for 28 days either natural-ingredient diets without PXC or supplemented with 1.5% or 3% PXC. Growth performance, blood biochemistry, caecal fermentation, morphology of the large intestine, and mucin gene expression were evaluated. PXC did not affect growth performance but tended to decrease relative liver weight. Among biochemical blood parameters, only bilirubin decreased and uric acid increased in response to 1.5% and 3% PXC, respectively. Caecal fermentation was not affected, with the exception of isovaleric acid concentration, which tended to be higher in rats fed the diet containing 3% PXC. Colonic crypts tended to be deeper in rats fed the 3% PXC diet and the thickness of the colonic mucus layer was reduced by both PXC levels. In conclusion, PXC did not affect growth performance or caecal fermentation but decreased thickness of the protective mucus layer in the colon.


Correction: Do women in science form more diverse research networks than men? An analysis of Spanish biomedical scientists.
[This corrects the article DOI: 10.1371/journal.pone.0238229.].


Suicide in elderly South Tyroleans in various residential settings at the time of death: a psychological autopsy study.
Completed suicide is more frequent among older adults than any other age group. Data on suicide in nursing homes and other residential facilities are inconsistent. This work aims to describe the characteristics of elderly suicide victims in different residential settings compared to young suicide victims. Data on people who died by suicide in the South Tyrol (Alto Adige) region of Italy between 2000 and 2009 were gathered from the local Provincial Mortality Register. Further detailed information was collected via questionnaires to mental health departments and psychological services, family physicians and relatives of the deceased. A total of 525 cases of suicide were recorded, with a linearly decreasing trend during the study period. About one-third of the suicides occurred in those aged 60 years and over. Suicide in the elderly was associated with low education level (odds ratio (OR) = 7.1, P < 0.001), living in a one-person household (OR = 2.4, P < 0.01), not having economic troubles (OR = 6.1, P < 0.01), having seen a doctor in the past month (OR = 2.4, P < 0.01) and living in a residential facility (OR = 2.6, P < 0.05). Twenty-four (17.9%) suicide victims aged 60 years and over were in a residential facility/hospital at the time of the death. They were more likely to be women, not married, and to die by jumping from a height. The suicide risk should be carefully assessed in the elderly who live alone or are institutionalized or hospitalized. Efforts are warranted to reduce seniors' access to high places in hospitals and facilities.


Characterization and Complete Genome Analysis of Pseudomonas aeruginosa Bacteriophage vB_PaeP_LP14 Belonging to Genus Litunavirus.
A lytic Pseudomonas aeruginosa phage vB_PaeP_LP14 belonging to the family Podoviridae was isolated from infected mink. The microbiological characterization revealed that LP14 was stable at 40 to 50 °C and stable over a broad range of pH (5 to 12). The latent period was 5 min, and the burst size was 785 pfu/infected cell. The whole-genome sequencing showed that LP14 was a dsDNA virus and has a genome of 73,080 bp. The genome contained 93 predicted open reading frames (ORFs), 17 of which have known functions including DNA replication and modification, transcriptional regulation, structural and packaging proteins, and host cell lysis. No tRNA genes were identified. BLASTn analysis revealed that phage LP14 had a high-sequence identity (96%) with P. aeruginosa phage YH6. Both morphological characterization and genome annotation indicate that phage LP14 is a memberof the family Podoviridae genus Litunavirus. The study of phage LP14 will provide basic information for further research on treatment of P. aeruginosa infections.


Distribution of Salmonella spp. Serotypes Isolated from Poultry in Abruzzo and Molise Regions (Italy) during a 6-Year Period.
Human salmonellosis incidence is increasing in the European Union (EU). Salmonellaenterica subsp. enterica serovar Enteriditis, Salmonellaenterica subsp. enterica serovar Typhimurium (including its monophasic variant) and Salmonellaenterica subsp. enterica serovar Infantis represent targets in control programs due to their frequent association with human cases. This study aimed to detect the most prevalent serotypes circulating in Abruzzo and Molise Regions between 2015 and 2020 in the framework of the Italian National Control Program for Salmonellosis in Poultry (PNCS)]. A total of 332 flocks of Abruzzo and Molise Regions were sampled by veterinary services in the period considered, and 2791 samples were taken. Samples were represented by faeces and dust from different categories of poultry flocks: laying hens (n = 284), broilers (n = 998), breeding chickens (n = 1353) and breeding or fattening turkeys (n = 156). Breeding and fattening turkeys had the highest rate of samples positive for Salmonella spp. (52.6%; C.I. 44.8%-60.3%). Faeces recovered through boot socks represented the greatest number of positive samples (18.2%). Salmonellaenterica subsp. enterica serovar Infantis was the prevalent serotype in breeding and fattening turkeys (32.7%; C.I. 25.8%-40.4%) and in broiler flocks (16.5%; C.I. 14.4%-19.0%). Salmonellaenterica subsp. enterica serovar Typhimurium was detected at low levels in laying hens (0.7%; C.I. 0.2%-2.5%) followed by breeding and fattening turkeys (0.6%; C.I. 0.2%-2.5%). Salmonellaenterica subsp. enterica serovar Enteriditis was also detected at low levels in laying hens (2.5%; C.I. 1.2%-5.0%). These findings highlight the role of broilers and breeding/fattening turkeys as reservoirs of Salmonella spp. and, as a consequence, in the diffusion of dangerous serotypes as Salmonellaenterica subsp. enterica serovar Infantis. This information could help veterinary services to analyze local trends and to take decisions not only based on indications from national control programs, but also based on real situations at farms in their own competence areas.


Ciclazindol: an oral agent with weight reducing properties and hypoglycaemic activity.
In a single blind crossover study, ciclazindol, 10-(m-chlorophenyl)-2, 3, 4, 10-tetrahydropyrimide (1, 2 alpha) indol-10-ol hydrochloride (Fig. 1), has been found to have hypoglycaemic action, and to produce reduction in appetite and weight. The mode of action appears to be different from either biguanides or sulphonylureas. Side-effects were few and mild. Metformin 500 mg b.d. had comparable hypoglycaemic effect but did not suppress appetite. Ciclazindol may be useful as a mild oral hypoglycaemic agent for obese patients, and would be suitable for once daily administration.


Toxicity of tributyltin chloride on haarder (Liza haematocheila) after its acute exposure: Bioaccumulation, antioxidant defense, histological, and transcriptional analyses.
Liza haematocheila is exposed to various chemical contaminants from anthropogenic sources, including tributyltin chloride (TBTC). Yet the toxicity mechanism of TBTC on haarder remains unclear. The haarder was exposed to different doses (0, 10%, 20%, and 50% of LC50-96 h) of TBTC. In this study, the results revealed its high bioaccumulation in the livers and significant alteration for development. The activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase decreased after 96-h exposure to TBTC, this accompanied by an increased malondialdehyde level. TBTC exposure caused the intense production of reactive oxygen species, a reduction in total blood cell count in serum, and apoptosis-related alterations in livers, indicating that enhanced oxidative stress occurred in the process of TBTC exposure. Histological results revealed angiorrhexis and infiltration of inflammatory cells, vacuolar degeneration of hepatocytes in the livers, and swelling, fusion, and disintegration of gill organs. Interestingly, the obtained transcriptional profiles indicated that high doses of TBTC caused energy disorder, apoptosis, and adipogenesis restriction mediated by cytokines and adipokines in Jak-STAT and adipocytokine signaling pathways. In summary, acute exposure to high doses of TBTC could impair the antioxidant system and pathways related to energy, apoptosis and adipogenesis, eventually posing a serious challenge to the fitness of haarder individuals and its fish populations as marine resources.


Exploiting Locusta migratoria as a source of bioactive peptides with anti-fibrosis properties using an in silico approach.
Edible insects have been proposed as an environmentally and economically sustainable source of protein, and are considered as an alternative food, especially to meat. The migratory locust, Locusta migratoria, is an edible species authorised by the European Union as a novel food. In addition to their nutritional value, edible insects are also sources of bioactive compounds. This study used an in silico approach to simulate the gastrointestinal digestion of selected L. migratoria proteins and posteriorly identify peptides capable of selectively inhibiting the N-subunit of the somatic angiotensin-I converting enzyme (sACE). The application of the molecular docking protocol enabled the identification of three peptides, namely TCDSL, IDCSR and EAEEGQF, which were predicted to act as potential selective inhibitors of the sACE N-domain and, therefore, possess bioactivity against cardiac and pulmonary fibrosis.


Possible Involvement of the CACNA1E Gene in Migraine: A Search for Single Nucleotide Polymorphism in Different Clinical Phenotypes.
To search for differences in prevalence of a CACNA1E variant between migraine without aura, various phenotypes of migraine with aura, and healthy controls. Familial hemiplegic migraine type 1 (FHM1) is associated with mutations in the CACNA1A gene coding for the alpha 1A (Cav 2.1) pore-forming subunit of P/Q voltage-dependent Ca2+ channels. These mutations are not found in the common forms of migraine with or without aura. The alpha 1E subunit (Cav 2.3) is the counterpart of Cav 2.1 in R-type Ca2+ channels, has different functional properties, and is encoded by the CACNA1E gene. First, we performed a total exon sequencing of the CACNA1E gene in three probands selected because they had no abnormalities in the three FHM genes. In a patient suffering from basilar-type migraine, we identified a single nucleotide polymorphism (SNP) in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760; Minor Allele Frequency 0.2241) hitherto not studied in migraine. In a second step, we determined its occurrence in four groups by direct sequencing on blood genomic DNA: migraine patients without aura (N = 24), with typical aura (N = 55), complex neurological auras (N = 19; hemiplegic aura: N = 15; brain stem aura: N = 4), and healthy controls (N = 102). The Asp859Glu - rs35737760 SNP of the CACNA1E gene was present in 12.7% of control subjects and in 20.4% of the total migraine group. In the migraine group it was significantly over-represented in patients with complex neurological auras (42.1%), OR 4.98 (95% CI: 1.69-14.67, uncorrected P = .005, Bonferroni P = .030, 2-tailed Fisher's exact test). There was no significant difference between migraine with typical aura (10.9%) and controls. We identified a polymorphism in exon 20 of the CACNA1E gene (Asp859Glu - rs35737760) that is more prevalent in hemiplegic and brain stem aura migraine. This missense variant causes a change from aspartate to glutamate at position 859 of the Cav 2.3 protein and might modulate the function of R-type Ca2+ channels. It could thus be relevant for migraine with complex neurological aura, although this remains to be proven.


The underfilled coronary artery: some pre- and post-operative observations on recipient arterial quality and left ventricular function after coronary artery surgery.
In a series of 141 saphenous vein aortocoronary bypass grafts in 59 patients undergoing routine restudy of the coronary arteries within four weeks of operation, an overall graft occlusion rate of 12% was found. A trend towards a higher occlusion rate was seen in arteries that were small (19%), that had a limited run-off (15%), significant distal disease (24%) or severe atheroma at the graft site (22%). Statistically, these occlusion rates are not significantly different from the overall failure rate and do not give absolute contra-indications to grafting. A particular group of arteries which seemed underfilled in the pre-operative angiogram (1.5 mm or less in diameter but apparently healthy with smooth walls and supplying a larger area of myocardium than would be expected from their apparent size) was identified. These arteries showed a significant increase in diameter in the post-operative angiograms and had a low occlusion rate (1 of 15 grafts; 7%). When all grafts were patent, the mean post-operative left ventricular ejection fraction showed a significant increase over the pre-operative valve, but when one or more grafts were occluded there was no significant change.


Ultrastructural study of the cornea in the chick embryo.
The study of the development of the cornea in the chick embryo by transmission and scanning electron microscopy allows us to observe the differences between the aspect of thin sections and the surface of the cells. When studied with the T.E.M. both endothelium and epithelium have a rather normal and mature aspects on the 9th day of development. Observed with the S.E.M., the aspect of the surface of the epithelium becomes mature no earlier than on the 19th day, whereas the development of the endothelium is completed only after hatching. The development of apical junctional complexes occurs at a later stage in the organisation of the endothelial layer.


Vestibular and visual signals in the ventral paraflocculus of the cerebellum in rabbits.
Extracellular microelectrode recordings from single cerebellar neurons were made in the ventral paraflocculus of anesthetized, paralyzed pigmented rabbits during vestibular and visual stimulation. The discharge of 6 out of 207 neurons was modulated during vestibular or visual stimulation. The activity of 5 neurons was modulated during vertical vestibular stimulation. The discharge of only one neuron was modulated exclusively during vertical optokinetic stimulation. The information from both the vestibular and visual systems which is received by the ventral paraflocculus appears to differ from that which is received by the flocculus in rabbits.


A role for antibody and Fc receptor in the clearance of Brugia malayi microfilariae.
The roles of antibodies (Ab) and Fc receptors (FcR) in clearance of Brugia malayi microfilariae (Mf) in vivo have not been previously elucidated. Different background strainsof mice clear Mf at different rates and we established that there were no major differences in Ab production between three particular strains. However, genetic immunodeficiencies in B cell and Ab production on each of these background strains significantly enhanced Mf survival. B cell-deficient microMT (C57BL/6) mice injected with B. malayi Mf i.v. retained significant numbers of live Mf in comparison to wild-type mice. Treatment of microMT mice with hyperimmune whole sera in the first week of infection significantly reduced the number of Mf surviving in the cardiac blood at 135 days p.i. Mf survival in FcRgamma-deficient (Sv129xC57BL/6) mice was also dramatically increased in the cardiac blood compared to wild-type mice, indicating that Ab itself is involved in Mf clearance most likely via a mechanism involving ADCC. These data indicate that Ab plays an important role in vivo in Mf killing in mice and this role is mediated via the FcR.


Angiogenic potential of Bambusa vulgaris leaves: Results of an in-vitro study with chicken embryo chorioallantoic membrane (CAM) model.
Herbal compounds have an important place in the management of wounds. However, very few compounds have been tested for their proangiogenic potential. The objective of study was to evaluate angiogenic potential of Bambusa vulgaris Schrad. plant extract. Chicken embryo chorioallantoic membrane model was used for estimation of angiogenic potential of B. vulgaris leaves extract with different concentrations. Angiogenic potential was estimated using focal application method and AbGel™ sponge application method. The test samples were loaded on eight embryonic development day of embryonic development of chick embryo and angiogenesis was observed on eleventh embryonic development day. Counting of blood vessels and photographic evaluation was done for estimation of angiogenic potential. The sponge specimen was examined for histological changes. Angiogenic potential of B. vulgaris leaves extract was compared against Plermin©. All tested concentrations (85 mcg, 170 mcg, 255 mcg, 340 mcg and 425 mcg/disc) of B. vulgaris showed angiogenic potential as indicated by increase in the number of blood vessels. Maximum growth in blood vessels was seen at the concentration of 255 mcg. Photographic evaluation showed changes in angiogenesis with B. vulgaris leaves extract. Angiogenic potential was also confirmed on histological examination. Plermin control groups also showed the growth of blood vessels measured by counting the number of blood vessels in photographic evaluation. The growth of blood vessels with Plermin 40 mcg was similar to B. vulgaris 255 mcg. The results of current study suggest angiogenic potential of B. vulgaris Schrad leaves as confirmed by visual observation and histological examination.


Cor triatriatum: masked by complex congenital cardiac anomalies.
The radiographic, angiographic, hemodynamic, and surgical features of 2 cases of cor triatriatum complicated by other cardiac anomalies are presented. In the first case, the patient had tetralogy of Fallot, the scimitar syndrome, and left ventricular obstruction. In the second case the patient had truncus arteriosus. The first case was revealed only after augmentation of pulmonary flow by an aorta-pulmonary artery anastomosis. In the second case, the diagnosis was retrospectively suggested by certain angiographic and hemodynamic clues. The prospective diagnosis was made only after a modified Rastelli procedure for truncus arteriosus. The difficulties encountered in making the diagnosis in both cases are discussed. It is stressed that a high index of suspicion, thorough accumulation and examination of hemodynamic data, and excellent angiograms and plain film radiography are all necessary to an early diagnosis of cor triatriatum when the latter is complicated by other congenital heart anomalies.


Factors affecting addiction severity index (ASI) among clients enrolled in methadone maintenance treatment (MMT) program in Myanmar.
Opioid substitution with methadone maintenance treatment (MMT) is shown to reduce illicit opioid use and renew social functioning. Understanding factors that undermine clients' social functioning during MMT treatment is vital for improving treatment compliance and quality of life. A total of 210 respondents who were already enrolled in a formal MMT program in Myanmar were recruited from five cities through stratified random sampling for this cross-sectional study. The addiction severity index (ASI) was used to objectively assess respondents social functioning in the last 30 days. Higher ASI scores denote poorer social functioning. Respondents total ASI scores in the respective domains were: employment (47.4%), alcohol (44.4%), drug use (7.2%), legal (49.2%) and social-family relationship (10.7%). Those reported to have never injected drugs in the last 30 days had lower ASI total scores than those who reported injection drug use (p = 0.01). After identifying the differences in ASI total scores, we found there were significant associations in the clients' hepatitis C status, age category, frequency of heroin injection, quality of life score, marital status, current leisure status with family/friend, current history of injection in the last 30 days, income status, satisfaction with current marital status, as well as reported drug and alcohol use (p < 0.05). Stepwise binary logistic regression showed that alcohol and higher frequency of heroin injection were associated with higher ASI scores. Meanwhile, older age, respondents those who had leisure time with family, and satisfied with current marital status had lower ASI scores (p < 0.05). Our results indicate that those enrolled in the MMT program in Myanmar faced many challenges in their daily social functioning. Treatment providers must take heed of these apparent impediment to ensure clients chequered social functioning does not undermine their treatment compliance. NA.


Detection of BCR/ABL rearrangements in adult acute lymphoblastic leukemia using a highly sensitive interphase fluorescence in situ hybridization method (D-FISH).
One hundred-and-six adult cases of acute lymphoblastic leukemia were prospectively investigated using a highly sensitive interphase fluorescence in situ hybridization assay which utilizes DNA probes that detect a double BCR/ABL fusion signal (D-FISH) in cells carrying the t(9;22) to evaluate the reliability and specificity of this method for the detection of the Ph translocation. The results were compared with those obtained in the same cases by conventional cytogenetics and by reverse-transcription polymerase chain reaction. The study was performed using DNA probes that span the common breakpoints of the t(9;22) translocation and that detect a double BCR/ABL fusion in cells carrying this karyotypic anomaly, one on the abnormal chromosome 9 and one on the Ph chromosome. Interphase D-FISH detected a high number of rearranged cases (22/106) compared to conventional cytogenetics (15/106) and RT-PCR (21/106). Interphase D-FISH emerges as a reliable, fast and relatively inexpensive tool for the detection of BCR/ABL rearrangements in adult ALL patients at diagnosis. It has a sensitivity clearly higher than conventional karyotyping and it may prove also superior to that of RT-PCR in cases with unusual BCR/ABL breakpoints. Our results suggest that D-FISH might be considered as the initial test for the diagnosis of Ph+ adult ALL.


Non-Hodgkin's lymphomas in children. II. Treatment.
The prognosis of non-Hodgkin's lymphoma (NHL) in childhood has improved steadily in the last 2 decades. This is primarily the result of increasingly effective chemotherapy regimens tailored to defined and relatively homogeneous prognostic categories and tested in prospective clinical trials. Surgical excision remains of prognostic benefit only when near-total resection can be performed without delay of chemotherapy. The role of radiation therapy is now limited to the treatment of overt central nervous system (CNS) lymphoma, disease unresponsive to chemotherapy, and certain emergencies. Effective 'prophylactic' treatment of the CNS has been achieved in most series by intrathecal and systemic chemotherapy alone. The most relevant modality of treatment is chemotherapy and a very large number of protocols have been published. The origins of current multi-agent regimens stem both from early experience with cyclophosphamide in endemic Burkitt's lymphoma and from therapeutic studies of acute lymphoblastic leukaemia. Sub-stratification of non-localized NHL has produced protocols designed for either lymphoblastic (mostly T cell) or non-lymphoblastic (mostly B cell) categories. While the cure rate for lymphoblastic lymphoma now exceed 70%, the non-localized non-lymphoblastic disease remains a major obstacle to cure. These patients frequently present with large abdominal primaries and are prone to regional as well as hematogenous dissemination. In particular, involvement of the CNS is now considered to be the most adverse prognostic variable in this group. Recently, highly intensive regimens are addressing these obstacles. On the other hand, NHL defined as localized has been shown to be curable in up to 95% of children with the use of simple chemotherapy regimens as short as 6 months in duration. Salvage of patients who relapse during or after chemotherapy remains bleak but cures are possible with regimens incorporating bone marrow transplantation from either an autologous or allogeneic source. Experimental methods, including biologic and immune response modifiers may also offer future promise.


Homocysteine in renovascular complications: hydrogen sulfide is a modulator and plausible anaerobic ATP generator.
Homocysteine (Hcy) is a non-protein amino acid derived from dietary methionine. High levels of Hcy, known as hyperhomocysteinemia (HHcy) is known to cause vascular complications. In the mammalian tissue, Hcy is metabolized by transsulfuration enzymes to produce hydrogen sulfide (H2S). H2S, a pungent smelling gas was previously known for its toxic effects in the central nervous system, recent studies however has revealed protective effects in a variety of diseases including hypertension, diabetes, inflammation, atherosclerosis, and renal disease progression and failure. Interestingly, under stress conditions including hypoxia, H2S can reduce metabolic demand and also act as a substrate for ATP production. This review highlights some of the recent advances in H2S research as a potential therapeutic agent targeting renovascular diseases associated with HHcy.


Bur1/Bur2 and the Ctk complex in yeast: the split personality of mammalian P-TEFb.
Eukaryotic organisms possess a host of factors that regulate transcriptional elongation. In higher eukaryotes, the transcription factor P-TEFb not only regulates phosphorylation of the RNA polymerase II C-terminal domain, but it also inhibits the action of transcriptional repressors and is required for the association of several elongation factors with the transcribing polymerase. In the yeast Saccharomyces cerevisiae, the cyclin dependent kinases Bur1/Bur2 and Ctk complex (Ctk1, 2 and 3) are also able to impact several aspects of transcription. Together, these two kinase complexes appear to functionally reconstitute the activity of P-TEFb in yeast. Recent findings regarding the role of these kinases in histone tail modifications and transcriptional regulation is briefly reviewed below.


Spermine with Sodium Taurocholate Enhances Pulmonary Absorption of Macromolecules in Rats.
The improvement effect of the combined use of spermine (SPM), a polyamine, with sodium taurocholate (STC) on the pulmonary drug absorption was investigated utilizing poorly absorbable drugs with various molecular sizes in rats. The pulmonary absorption of rebamipide, a low molecular but poorly absorbable drug after oral administration, was significantly improved by the combined use of SPM with STC (SPM-STC formulation), while poly- L-lysine did not show a significant change in rebamipide absorption from the lungs. Furthermore, the safety of the SPM-STC formulation for the lungs was assessed in rats by the histopathological study and any local toxicity was not observed while poly-L-lysine, a typical chemical causing the toxicity for the epithelial cells, provided several histopathological changes. In addition, the SPM-STC formulation significantly improved the pulmonary absorption of fluorescein isothiocyanate dextran 4 (FD-4, Mw ca 4000) and interferon-α (IFN-α, Mw ca 25,000) as well. Our present results clearly indicated that the SPM-STC formulation significantly improved the pulmonary absorption of poorly absorbable small and large molecular drugs without any harmful effects on the lungs. Therefore, the SPM-STC formulation would be a useful one for the pulmonary absorption of drugs, specifically macromolecular ones, which are very difficult to be absorbed after oral administration.


Yellow nail syndrome accompanied by minimal-change nephrotic syndrome: A case report.
In most cases of yellow nail syndrome (YNS), the classic triad of yellow nails, lymphedema and respiratory manifestations rarely manifest simultaneously. Therefore, diagnosis is delayed or frequently missed. We report a 62-year-old YNS patient presenting with bilateral pleural, pericardial and peritoneal effusions who, 2 mo later, developed minimal-change nephrotic syndrome. After treatment with vitamin E, clarithromycin and prednisone for 3 mo, effusions in the chest, pericardium and abdominal cavity decreased while urine protein levels returned to within normal ranges. Clinicians should consider the possibility of YNS for patients presenting with multiple serous effusions and nephrotic syndromes.


Oncogenic viruses and chemoresistance: What do we know?
Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.


Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.
Greater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta-analysis compared aIMT in youth with type 1 diabetes and healthy controls. A systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta-analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection. Meta-analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure. Type 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559).


Low intraovarian vascular resistance: a marker for severe ovarian hyperstimulation syndrome.
To assess intraovarian blood flow in relation to the severity of ovarian hyperstimulation syndrome (OHSS) after controlled ovarian hyperstimulation. A prospective study. Monash IVF, Clayton, Victoria, Australia. Thirty patients with OHSS after embryo or gamete transfer who also had sonographic evidence of ascites. The resistance to blood flow within the ovaries of 11 patients with severe OHSS and 19 patients with mild OHSS was measured by using transabdominal ultrasonography with color flow and pulsed Doppler imaging. The pulsatility index (PI), resistance index (RI), and the S-D ratio, all measures of downstream vascular impedance, were significantly lower in those patients with severe OHSS. In cases with RI < 0.48, more than two thirds of the patients had a pleural effusion, whereas patients with either PI < 0.75 or S-D < 1.92 had pleural effusion in over one half of the cases. It was notable that blood flow velocity did not differ significantly between the two groups despite the changes in vascular impedance. There appears to be a close correlation between the severity of OHSS and the resistance to blood flow within the stimulated ovaries. Measurement of intraovarian vascular resistance before gamete transfer or ET in patients undergoing controlled ovarian hyperstimulation may help in predicting those patients at particular risk of developing severe OHSS.


Active coatings of thermoplastic starch and chitosan with alpha-tocopherol/bentonite for special green coffee beans.
The quality of green coffee beans (GCBs) is possibly affected by storage conditions. Edible polymer coatings for GCBs can help preserve flavors and improve shelf life of GCBs. This study aimed to incorporate α-tocopherol, a powerful antioxidant, in thermoplastic starch [TPS] and chitosan [TPC] and determined the best cavitation energy (960-3840 J·mL-1) using an ultrasonic probe. Then, we evaluated the incorporation of bentonite (0% and 2% m/m) and α-tocopherol (0% and 10% m/m) in the best energy cavitation/biopolymer combination. The TPS and TPC coatings demonstrated good adherence to the GCBs, measured by surface energy. The dispersion of α-tocopherol in TPC, with cavitation energy 960 J·mL-1, promoted greater stability (greater zeta potential), thereby increasing antioxidant activity by 28% compared to TPS, therefore, was selected for a second stage. Incorporation of 2% bentonite into the TPC, with 10% α-tocopherol, resulted in a 3.7 × 10-10 g·m-1·s-1·Pa-1 water vapor permeability, which is satisfactory for prevented of moisture gain during storage. The compressive load showed values of 375 N to the non-coated GCB and around 475 N with the insertion of coatings to the GCB. Thus, a TPC/α-tocopherol/bentonite combination, dispersed with 960 J·mL-1 energy, was highly effective in the development of biopolymeric coatings for the GCBs.


A case series of symptomatic intraluminal duodenal duplication cysts: presentation, endoscopic therapy, and long-term outcome (with video).
Duodenal duplication cysts are rare congenital anomalies. Symptomatic cases have classically been treated by surgical resection, which can be complex because of the close proximity of the cysts to the papilla. To describe a series of 8 patients with symptomatic duodenal duplication cysts who were treated endoscopically, with a special focus on the long-term outcome. Retrospective case series. Three tertiary-care European academic hospitals. Eight patients, age 8 to 72 years, were treated endoscopically for symptomatic intraluminal duodenal duplication cysts between 1981 and 2006. Seven patients presented with acute pancreatitis, and one patient presented with jaundice. Endoscopic incision and marsupialization of the cysts was performed by using a variety of endoscopic tools (needle-knife and regular sphincterotomes, cystotomes, and polypectomy snares). Technical success of endoscopic intervention and long-term clinical recurrence of symptoms. No major complications occurred. All patients remained asymptomatic at a median follow-up of 7.3 years. Retrospective study; the small number of patients. The endoscopic treatment of symptomatic intraluminal duodenal duplication cysts is a safe and effective technique, with excellent long-term results. It represents a minimally invasive alternative to surgical resection and might be considered the preferred therapeutic modality for these cases.


Retardation of ethanol absorption by food in the stomach.
Ethanol diffusion from rat stomachs containing food particles was slower than from empty stomachs, and blood alcohol concentrations were lower in fed than in fasted rats given ethanol by gavage.


OntologyWidget - a reusable, embeddable widget for easily locating ontology terms.
Biomedical ontologies are being widely used to annotate biological data in a computer-accessible, consistent and well-defined manner. However, due to their size and complexity, annotating data with appropriate terms from an ontology is often challenging for experts and non-experts alike, because there exist few tools that allow one to quickly find relevant ontology terms to easily populate a web form. We have produced a tool, OntologyWidget, which allows users to rapidly search for and browse ontology terms. OntologyWidget can easily be embedded in other web-based applications. OntologyWidget is written using AJAX (Asynchronous JavaScript and XML) and has two related elements. The first is a dynamic auto-complete ontology search feature. As a user enters characters into the search box, the appropriate ontology is queried remotely for terms that match the typed-in text, and the query results populate a drop-down list with all potential matches. Upon selection of a term from the list, the user can locate this term within a generic and dynamic ontology browser, which comprises the second element of the tool. The ontology browser shows the paths from a selected term to the root as well as parent/child tree hierarchies. We have implemented web services at the Stanford Microarray Database (SMD), which provide the OntologyWidget with access to over 40 ontologies from the Open Biological Ontology (OBO) website 1. Each ontology is updated weekly. Adopters of the OntologyWidget can either use SMD's web services, or elect to rely on their own. Deploying the OntologyWidget can be accomplished in three simple steps: (1) install Apache Tomcat 2 on one's web server, (2) download and install the OntologyWidget servlet stub that provides access to the SMD ontology web services, and (3) create an html (HyperText Markup Language) file that refers to the OntologyWidget using a simple, well-defined format. We have developed OntologyWidget, an easy-to-use ontology search and display tool that can be used on any web page by creating a simple html description. OntologyWidget provides a rapid auto-complete search function paired with an interactive tree display. We have developed a web service layer that communicates between the web page interface and a database of ontology terms. We currently store 40 of the ontologies from the OBO website 1, as well as a several others. These ontologies are automatically updated on a weekly basis. OntologyWidget can be used in any web-based application to take advantage of the ontologies we provide via web services or any other ontology that is provided elsewhere in the correct format. The full source code for the JavaScript and description of the OntologyWidget is available from http://smd.stanford.edu/ontologyWidget/.


Premenstrual depression, cortisol and oestradiol treatment.
A woman with a 5-year history of frequently recurrent depressions responded poorly to the usual antidepressants. She had a raised plasma cortisol and was made worse by progesterone or by ACTH. An oestradiol/testosterone implant every 4 months abolished all symptoms for at least 8 years, and plasma cortisol returned to normal. This case is relevant to an understanding of premenstrual syndromes and the genesis of depressive illness.


The iron metabolism of neoplastic cells: alterations that facilitate proliferation?
For many years it has been known that neoplastic cells express high levels of the transferrin receptor 1 (TfR1) and internalize iron (Fe) from transferrin (Tf) at a tremendous rate. Considering the high requirement of neoplastic cells for Fe, understanding its metabolism is vital in terms of devising potential new therapies. Apart from TfR1, a number of molecules have been identified that may have roles in Fe metabolism and cellular proliferation. These molecules include transferrin (Tf), the oestrogen-inducible transferrin receptor-like protein, transferrin receptor 2 (TfR2), melanotransferrin (MTf), ceruloplasmin, and ferritin. In the present review these latter molecules are discussed in terms of their potential functions in tumour cell Fe metabolism and proliferation. Further studies are essential to determine the specific roles of these proteins in the pathogenesis of cancer.


Treated vs reported toxic exposures: discrepancies between a poison control center and a member hospital.
Statistics accumulated by Poison Control Centers (PCC) are routinely used on the local, regional and national levels by governmental agencies to set policy and direct funding. Incomplete reporting by member hospitals is recognized by PCC as a factor contributing to discrepancies in epidemiological estimates; however little emphasis is classically placed by the PCC on expanding reporting from member hospitals. A 1y retrospective review of patients with toxic exposure presenting to an urban Emergency Medicine Department (EMD) was performed to quantify the lack of concordance between treated and reported toxic exposures. 470 toxic exposures presented over the study period, of which only 123 (26%) were relayed to the regional PCC. Inhalation exposures were least likely to be referred for PCC consultation (3%); whereas PCC consultation was obtained for 33% venomous snake bite cases, and 95% of the cyclic antidepressant ingestions. Clusters of similar exposures resulted in fewer PCC consultations. Understanding each hospital's "profile" for handling toxic exposures, and individualized advertisement by the PCC to their member hospital may increase their data reporting. The statistical significance of their epidemiological studies as well as their revenue may increase.


Tracheostomy decannulation to noninvasive positive pressure ventilation in congenital central hypoventilation syndrome.
Noninvasive positive pressure ventilation (NPPV) may permit tracheostomy decannulation (TD) in patients with congenital central hypoventilation syndrome (CCHS) requiring nocturnal positive pressure ventilation via tracheostomy (PPV-T). There is limited evidence on optimal strategies for transitioning patients from PPV-T to NPPV. This study aimed to describe the clinical course and outcome of children with CCHS who underwent TD and transitioned from PPV-T to NPPV. Retrospective review was conducted on patients with CCHS using nocturnal PPV-T who underwent TD to NPPV. The results of clinical evaluations, airway endoscopy, polysomnography, and clinical course leading to TD were analyzed. We identified 3 patients with CCHS aged 8-17 years who required PPV-T only during sleep. Patients underwent systematic multidisciplinary evaluations with a pediatric psychologist, pulmonologist, sleep physician, and otolaryngologist utilizing a TD algorithm. These included evaluation in the sleep clinic, NPPV mask fitting and desensitization, endoscopic airway evaluation, daytime tracheostomy capping, acclimatization to low-pressure NPPV, polysomnography with capped tracheostomy and NPPV titration, and if successful, TD. All patients underwent successful TD following optimal titration of NPPV during polysomnography. The duration to TD from decision to pursue NPPV was between 2.4 and 10.6 months, and the duration of hospitalization for TD was between 4 and 5 days. There were no NPPV-related complications; however, all patients required surgical closure of tracheocutaneous fistula. NPPV may be an effective and feasible option for patients with CCHS requiring PPV-T during sleep and permits TD. In patients with CCHS, a systematic multidisciplinary algorithm may optimize successful transition to NPPV and TD.


Design and characterization of a salicylic acid-inducible gene expression system for Jurkat cells.
With continued progress in cell and gene therapies, there is an immediate need for exogenously tunable gene expression systems with safe and predictable behavior in specific human cell types. Here, we demonstrate the ability of the salicylic acid (SA)-inducible MarR repressor protein from Escherichia coli to regulate target gene expression in a human T lymphocyte cell line. Two lentiviral vectors, one encoding an enhanced green fluorescent protein (EGFP) reporter cassette and the other a repressor cassette, were sequentially transduced into Jurkat cells, using fluorescence-activated cell sorting (FACS) to isolate stable Jurkat progeny. As a result, EGFP expression was repressed by MarR and was inducible upon the addition of SA (~1.3 fold). This represents the first example of functional expression of bacterial MarR in mammalian cells, and opens the possibility for further development of regulated, SA-tunable gene expression system for T-cells.


Resting heart rates in an ambulatory elderly population: an evaluation of age, sex, symptoms, and medication.
In a cross-sectional analysis of 2,301 ambulatory elderly subjects, the mean resting heart rate for women (66.2/min) was significantly higher than for men (63.6/min), p less than 0.0001, and heart rate was positively correlated with age for both men and women. Resting heart rate was positively correlated with the number of drugs used (p less than 0.05), number of symptoms reported (p less than 0.05), systolic (p less than 0.01), and diastolic (p less than 0.0001) blood pressure. Of 975 participants who were followed longitudinally over an 8-year period there was a significant decrease in resting heart rate of approximately 2.75/min, p less than 0.0001.


A Survey of Provider-Reported Use and Perceived Effectiveness of Medications for Symptom Management in Telemedicine and Outpatient Visits for Mild COVID-19.
Many patients with mild coronavirus disease 2019 (COVID-19) have symptoms requiring acute and follow-up care. The aims of this study were to assess (1) provider-reported use of medications and their perceived effectiveness and (2) degree of difficulty managing specific symptoms at episodic COVID-19 care sites and in a longitudinal monitoring program. We sent an online survey to physicians, advanced practice providers, and registered nurses redeployed to COVID-19 care sites at an academic medical center from March to May 2020. We asked about the use of medications and perceived effectiveness of medications to treat symptoms of COVID-19 and the perceived challenge of symptom management. Comparison was made by provider type (episodic or longitudinal site of care). Responses from 64 providers were included. The most frequently used medications were acetaminophen (87.1% of respondents), benzonatate (83.9%), and albuterol metered dose inhalers (MDI) (80.6%). Therapies for lower respiratory tract symptoms were reported as more commonly used by longitudinal follow-up providers compared to episodic providers including guaifenesin (90.6% vs 60.0%, p = 0.007), benzonatate (93.8% vs 73.3%, p = 0.04), nebulized albuterol for patients with asthma (75.0% vs 43.3%, p = 0.019), and albuterol MDIs for patients without asthma (90.6% vs 66.7%, p = 0.029). Medications found to have the highest perceived efficacy by respondents using the therapy (> 80% reporting "very efficacious") included albuterol, acetaminophen for fever, non-sedating antihistamines, nasal steroid spray, and non-steroidal anti-inflammatory drugs (NSAIDs) for myalgia, arthralgia, or headache. Lower respiratory symptoms and anxiety were rated as the most challenging symptoms to manage. Providers reported that clinical care of mild COVID-19 with medications in common use for other respiratory infections is effective, both at episodic care and longitudinal sites of care, but that specific symptoms are still challenging to manage.


Comparative evaluation of physical characteristics and volatile flavor components of Bangia fusco-purpurea subjected to hot air drying and vacuum freeze-drying.
Bangia fusco-purpurea is an economically important seaweed with Fujian characteristics. Given that its harvest is seasonal, drying is often used to remove moisture, extend storage time, and facilitate further processing. Hence, the current study sought to explore the impact of different drying processes on the quality and volatile fingerprints of Bangia fusco-purpurea. To this end, the effects of hot air drying (HAD) and vacuum freeze drying (VFD) on the drying characteristics, microstructure, rehydration, and volatile components of dried B. fusco-purpurea were investigated. The results showed that the water removal efficiency of HAD was significantly higher than that of VFD. However, VFD better preserved the skeletal structure of B. fusco-purpurea than HAD, with a faster rehydration rate and a more uniform cell structure after rehydration. Using electronic nose and comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOF MS), significant differences in the volatile profiles of fresh, HAD, and VFD B. fusco-purpurea were assessed. E-nose analysis revealed that both HAD and VFD treatments significantly reduced sulfides, aromatic compounds, and nitrogen oxides in fresh B. fusco-purpurea. However, the alcohol, aldehyde, and ketone contents were lower in the VFD samples compared with HAD and fresh samples, whereas the content of methyl flavor substances was significantly higher. GC × GC-TOF MS analysis revealed that the most abundant volatile categories in HAD and VFD were hydrocarbons, alcohols, and esters. The number of volatile components in the HAD samples was significantly lower than in the VFD and fresh samples. As drying progressed, hydrocarbons and alcohols were formed in dried B. fusco-purpurea due to the thermal degradation of carbohydrates, lipids, amino acids, and the Maillard reaction. There were also significant flavor differences between HAD and VFD B. fusco-purpurea. Thus, although HAD exhibits better drying efficiency, VFD has more significant advantages in terms of product quality.


Association of Insulin Resistance with Serum Interleukin-6 and TNF-α Levels During Normal Pregnancy.
The purpose of this study was to evaluate the role of Tumor Necrosis Factor-α (TNF-α) in insulin resistance (IR) during normal pregnancy. This cross sectional study was carried out on 86 healthy pregnant women including 26, 23 and 37 individuals in the 1st, 2nd and 3rd trimesters, respectively, and in 21 healthy non pregnant women. Serum TNF-α concentration was measured by Enzyme Linked Immunosorbent Assay (ELISA) method. There were significant differences between serum TNF-α and IL-6 levels in pregnant women as compared with maternal healthy controls. There was significant correlation between gestational age and Body Mass Index (BMI) (r = 0.28, P = 0.01). There was no significant correlation between gestational age and insulin resistance (IR). We also did not find correlations between IR and TNF-α and IR and IL-6 in pregnant women. In conclusion, our findings suggest that TNF-α and IL-6 are not greatly contributed to pregnancy induced insulin resistance in normal pregnancy.


Xanthine dehydrogenase from Drosophila melanogaster: a comparison of the kinetic parameters of the pure enzyme from two wild-type isoalleles differing at a putative regulatory site.
Xanthine dehydrogenase (XDH) from Drosophila melanogaster has been purified to homogeneity by immunoaffinity chromatography, and its kinetic parameters determined. Drosophila XDH exhibits ordered binding for substrate and NAD+, analogous to the corresponding enzymes from vertebrate sources. The wild-type enzyme exhibits a Km for xanthine of 2.4 X 10(-5) M, and for NAD+ of 4.0 X 10(-5) M. XDH purified from a genetic variant exhibiting elevated levels of enzyme activity has similar kinetic constants. The results provide further evidence that the site of variation in the latter strain results in higher steady state numbers of XDH molecules per fly.


Clinical characteristics of vascular leiomyoma of the upper extremity: report of 11 cases.
Clinical features of vascular leiomyoma of the upper extremity which have not been described or have been described incorrectly are documented with a report of 11 consecutive cases seen within the past 11 years. All patients were followed without recurrence or surgical morbidity. Vascular leiomyoma has been described as a painful nodule found more frequently on the extensor surfaces, but in our experience spontaneous or paroxysmal pain is exceptional and the tumour tends to be located on the volar surface when it is in the hand. In the digit, they tend to be found at the base away from the midline, and not seen distal to the DIP joint.


A network-based model of dynamic cerebral autoregulation.
Cerebrovascular diseases continue to be one of the leading causes of morbidity and mortality in humans. Abnormalities in dynamic cerebral autoregulation (dCA) have been implicated in many of these disease conditions. Accurate models are therefore needed to better understand the complex pathophysiology behind impaired dCA. We thus present here a simple framework for modelling a vessel-driven network model of dCA in the microvasculature, as opposed to the conventional compartmental modelling approach. Network models incorporate the actual connectivity and anatomy of the vasculature, thereby allowing us to include and trace changes in the calibre and morphology of individual vessels, investigate the spatial specificity and heterogeneity of the various control mechanisms to help disentangle their contributions, and link the model parameters to the actual network physiology. The proposed control feedback mechanisms are incorporated at the level of the individual vessel, and the dynamic pressure and flow fields are solved for here within a simple vessel network. In response to an upstream pressure drop, the network is found to be able to recover cerebral blood flow (CBF) while exhibiting the characteristic autoregulatory behaviour in terms of changes in vessel calibre and the biphasic flow response. We assess the feasibility of our formulation in larger networks by comparing the simulation results to those obtained using a one-dimensional (1D) model of CBF applied to the same microvasculature network and find that our model results are in very good agreement with the 1D solution, while significantly reducing the computational cost, thus enabling more detailed models of network behaviour to be adopted in the future. Accurate and computationally feasible models of dCA that are more representative of the vasculature can help increase the translatability of haemodynamic models into the clinical environment, which would help develop more informed treatment guidelines for patients with cerebrovascular diseases.


Uptake of endocytic markers into mitotic yeast cells.
[3H]alpha-Factor and Lucifer yellow were used to measure receptor mediated and fluid-phase endocytosis in the yeast Saccharomyces cerevisiae, arrested in mitosis by depolymerization of the microtubules or due to a mutation preventing nuclear division (cdc16). Both processes continued at roughly the same level as during interphase. This shows that in yeast endocytosis is not interrupted during mitosis like in mammalian cells.


Inconsistency between different measures of sexual selection.
Measuring the intensity of sexual selection is of fundamental importance to the study of sexual dimorphism, population dynamics, and speciation. Several indices, pools of individuals, and fitness proxies are used in the literature, yet their relative performances are strongly debated. Using 12 independent common lizard populations, we manipulated the adult sex ratio, a potentially important determinant of the intensity of sexual selection at a particular time and place. We investigated differences in the intensity of sexual selection, as estimated using three standard indices of sexual selection-the standardized selection gradient (β'), the opportunity of selection (I), and the Bateman gradient (βss)--calculated for different pools of individuals and different fitness proxies. We show that results based on estimates of I were the opposite of those derived from the other indices, whereas results based on estimates of β' were consistent with predictions derived from knowledge about the species' mating system. In addition, our estimates of the strength and direction of sexual selection depended on both the fitness proxy used and the pool of individuals included in the analysis. These observations demonstrate inconsistencies in distinct measures of sexual selection and underscore the need for caution when comparing studies and species.


Elsinoe takoropuku sp. nov. infects twigs of Pittosporum tenuifolium in New Zealand.
Elsinoe takoropuku sp. nov. is described from Pittosporum tenuifolium Sol. ex Gaertn. (Pittosporaceae). This species causes swelling to develop on the twigs of the host species. The species initially was thought to be a recent introduction to New Zealand but, based on the host association and the geographic range of the fungus in New Zealand, it is considered to be a newly described native species.


Is there a relationship between opioid use and transient global amnesia?
Opioid-associated amnestic syndrome (OAS) and transient global amnesia (TGA) are conditions with clinical overlap. We therefore sought to determine whether opioid use might be associated with TGA. Data from the Massachusetts Department of Public Health Syndromic Surveillance program were queried to ascertain the frequency of opioid use among emergency department (ED) encounters for TGA compared to that for all other ED visits between January 2019 and June 2023. A total of 13,188,630 ED visits were identified during the study period. Of 1417 visits for TGA, one visit met the exposure definition for opioid use. There were 13,187,213 visits for other indications, 57,638 of which were considered opioid-exposed. The odds ratio for the relationship between opioid use and TGA was 0.16 (95% confidence interval 0.02, 1.14). Despite the clinical overlap between OAS and TGA, surveillance data from ED visits in Massachusetts do not suggest that opioid use is a risk factor for TGA, indicating that OAS and TGA are distinct entities.


Urethral reconstruction before renal transplantation.
Herein we report the first case of reconstruction of a long-standing transected proximal urethra, following a pelvic fracture and resultant rectourethral fistula before renal transplantation. This case supports the viewpoint that before creation of a supravesical diversion in potential transplant patients with lower urinary tract dysfunction, reconstruction of the lower urinary tract should be attempted when there is a reasonable chance for successful outcome.


First Identification of the New Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant (B.1.1.529) in Italy.
We identified the first case in Italy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 variant, using whole-genome sequencing in an Italian subject traveling from Mozambique. Specific mutation profiles deserve further investigations to clarify potential effects on vaccination efficacy. This case highlights the crucial role of rapid and continuous surveillance of SARS-CoV-2 variant circulation.


Preventing sexual violence: can examination of offense location inform sex crime policy?
Recently, legislative initiatives to prevent sex crime recidivism include the passage of child safety zones (also called loitering zones) that prohibit sex offenders from lingering near places where children congregate. The ability of policies such as these or residence restrictions to curb sexual recidivism depends on the empirical reality of sex offender perpetration patterns. As such, the current study sought to examine locations where sex offenders first come into contact with their victims and whether sex crime locations differ among those who perpetrate offenses against children as compared to those who perpetrate offenses against adults. Further, this study examined actuarial risk scores and recidivism rates among offenders who met victims in child-dense public locations to determine if these offenders are more at risk of re-offense. Descriptive analyses, based on archival sex offender file review (N=1557), revealed that offenders primarily cultivated their offenses in private residential locations (67.0%); relatively few offenders (4.4%) met their victims in child-dense public locations. Further, offenders who perpetrated crimes against children were more likely to meet victims within a residence, while those who perpetrate crimes against adults were more likely to encounter victims in a more public type of location (e.g., bar, workplace). Though only 3.7% of all offenders in this sample sexually recidivated, those who recidivated were more likely to have met their victim in a child-dense public location than those who did not recidivate. Current sex crime policies that focus only on where offenders live may fail to focus on where offenders go and, further, may misdirect efforts away from the place where sex crimes most often occur, namely, in the home.


Forceful patterning in mouse preimplantation embryos.
The generation of a functional organism from a single, fertilized ovum requires the spatially coordinated regulation of diverse cell identities. The establishment and precise arrangement of differentiated cells in developing embryos has, historically, been extensively studied by geneticists and developmental biologists. While chemical gradients and genetic regulatory networks are widely acknowledged to play significant roles in embryo patterning, recent studies have highlighted that mechanical forces generated by, and exerted on, embryos are also crucial for the proper control of cell differentiation and morphogenesis. Here we review the most recent findings in murine preimplantation embryogenesis on the roles of cortical tension in the coupling of cell-fate determination and cell positioning in 8-16-cell-stage embryos. These basic principles of mechanochemical coupling in mouse embryos can be applied to other pattern formation phenomena that rely on localized modifications of cell polarity proteins and actin cytoskeletal components and activities.


Upregulation of bradykinin receptors is implicated in the pain associated with caerulein-induced acute pancreatitis.
Although the way for pain management associated with acute pancreatitis has been searched for, there are not enough medications available for it. The aim of the present study was to investigate the role of bradykinin (BK) in pain related to acute pancreatitis. After repeated injections of caerulein (50 μg/kg and 6 times), mice showed edema in the pancreas, and blood concentrations of pancreatic enzymes (amylase and lipase) were clearly elevated. A histopathological study demonstrated that caerulein caused tissue damage characterized by edema, acinar cell necrosis, interstitial hemorrhage, and inflammatory cell infiltrates. Furthermore, the mRNA levels of interleukin-1β and monocyte chemotactic protein (MCP)-1 were significantly increased in the pancreas of caerulein-treated mice. The sensitivity of abdominal organs as measured by abdominal balloon distension was enhanced in caerulein-injected mice, suggesting that caerulein caused pancreatic hyperalgesia. Moreover, repeated treatment with caerulein resulted in cutaneous tactile allodynia of the upper abdominal region as demonstrated by the use of von Frey filaments, indicating that caerulein-treated mice exhibited referred pain. Under this condition, the mRNA levels of bradykinin B1 receptor (BKB1R) and bradykinin B2 receptor (BKB2R) were significantly increased in the dorsal root ganglion (DRG). Finally, we found that des-Arg⁹-(Leu⁸)-bradykinin (BKB1R antagonist) and HOE-140 (BKB2R antagonist) attenuated the acute pancreatitis pain-like state in caerulein-treated mice. These findings suggest that the upregulation of BK receptors in the DRG may, at least in part, contribute to the development of the acute pancreatitis pain-like state in mice.


Autoradiographical evaluation of [3H]glycine uptake in rat forebrain: cellular localization in the hippocampus.
The cellular elements responsible for the uptake of [3H]glycine into rat hippocampal slices were investigated. The diffuse laminar distribution of labelling observed under control conditions was greatly reduced seven days after intrahippocampal injection of a neurotoxic dose of quinolinic acid, suggesting a neuronal localization. Glycine was also taken up into glial cells, since dense clusters of silver grains were present on small sized cells throughout the hippocampus which were apparently increased in number after the lesion. The pattern of [3H]glycine uptake into rat cerebral cortex and cerebellar slices was also consistent with both neuronal and glial localization. These glycine transport sites may be strategically located to control excitatory neurotransmission mediated by the N-methyl-D-aspartate sub-type of glutamate receptors.


Freezing of nonlinear Bloch oscillations in the generalized discrete nonlinear Schrödinger equation.
The dynamics in a nonlinear Schrödinger chain in a homogeneous electric field is studied. We show that discrete translational invariant integrability-breaking terms can freeze the Bloch nonlinear oscillations and introduce new faster frequencies in their dynamics. These phenomena are studied by direct numerical integration and through an adiabatic approximation. The adiabatic approximation allows a description in terms of an effective potential that greatly clarifies the phenomena.


Priming of camalexin accumulation in induced systemic resistance by beneficial bacteria against Botrytis cinerea and Pseudomonas syringae pv. tomato DC3000.
Plants harbor various beneficial microbes that modulate their innate immunity, resulting in induced systemic resistance (ISR) against a broad range of pathogens. Camalexin is an integral part of Arabidopsis innate immunity, but the contribution of its biosynthesis in ISR is poorly investigated. We focused on camalexin accumulation primed by two beneficial bacteria, Pseudomonas fluorescens and Bacillus subtilis, and its role in ISR against Botrytis cinerea and Pseudomonas syringae Pst DC3000. Our data show that colonization of Arabidopsis thaliana roots by beneficial bacteria triggers ISR against both pathogens and primes plants for enhanced accumulation of camalexin and CYP71A12 transcript in leaf tissues. Pseudomonas fluorescens induced the most efficient ISR response against B. cinerea, while B. subtilis was more efficient against Pst DC3000. Analysis of cyp71a12 and pad3 mutants revealed that loss of camalexin synthesis affected ISR mediated by both bacteria against B. cinerea. CYP71A12 and PAD3 contributed significantly to the pathogen-triggered accumulation of camalexin, but PAD3 does not seem to contribute to ISR against Pst DC3000. This indicated a significant contribution of camalexin in ISR against B. cinerea, but not always against Pst DC3000. Experiments with Arabidopsis mutants compromised in different hormonal signaling pathways highlighted that B. subtilis stimulates similar signaling pathways upon infection with both pathogens, since salicylic acid (SA), but not jasmonic acid (JA) or ethylene, is required for ISR camalexin accumulation. However, P. fluorescens-induced ISR differs depending on the pathogen; both SA and JA are required for camalexin accumulation upon B. cinerea infection, while camalexin is not necessary for priming against Pst DC3000.


Changes in body condition score from calving to first insemination and milk yield, pregnancy per AI, and pregnancy loss in lactating dairy cows: A meta-analysis.
We determined the association of body condition score (BCS) at calving, at first postpartum artificial insemination (AI), and change in BCS between calving and first AI on pregnancy per AI (P/AI) at 30-45 d, pregnancy loss to 60-85 d, and milk yield in lactating dairy cows. Outcome data were included from 15 studies and 47 herd-year combinations. Additional variables included season of AI, herd, days in milk at first AI, parity, and of mean daily milk yield within 2 wk of first AI. The BCS scale employed was a standard 1-5 scale (1 = severe under conditioning or emaciated and 5 = severe over conditioning) with 0.25 cut points. Presynchronization treatments that included PGF2α and GnRH increased (P < 0.05) the proportion of cows with luteal function before AI compared with PGF2α alone. Compared with no presynchronization treatment those that included PGF2α or PGF2α and GnRH increased (P < 0.05) first P/AI. Cows having BCS ≥2.75 at AI had greater (P < 0.01) first P/AI than cows with BCS <2.75. As BCS at first AI increased, P/AI increased in a linear (P = 0.04) fashion and was greater in cows expressing estrus when BCS at AI was <2.50. Presynchronization had no association with P/AI for cows with BCS at calving <3.00 compared with those with BCS ≥3.00. In contrast, multiparous cows tended (P = 0.06) to have greater P/AI when they calved with BCS ≥3.00 compared with <3.00. Increasing BCS at AI was associated with decreased (P = 0.01) pregnancy loss. Pregnancy per AI did not differ among cows according to the magnitude of prebreeding BCS loss, but more multiparous cows losing more than 0.5 units of BCS tended to have greater pregnancy losses in second-parity cows (P = 0.09) and in cows of third or greater (P < 0.001) parity. Daily milk yields at first AI differed among parities as expected, but a parity by BCS at calving interaction was detected (P = 0.008). Daily milk yield at first AI decreased (P < 0.001) linearly as BCS at AI increased, with an exacerbated greater negative effect during summer. More prebreeding loss in BCS was associated with more (P < 0.05) milk yield in first- and second-parity cows. We concluded that greater BCS at first AI was associated with improved P/AI, but magnitude of prebreeding BCS loss was not associated with P/AI. In contrast, more pregnancy loss was associated with more prebreeding BCS loss in multiparous cows. Cow having lesser BCS at AI and greater prebreeding loss in BCS produced more milk than their herd mates of greater BCS and lesser prebreeding loss in BCS, respectively.


Respiratory syncytial virus and TNF alpha induction of chemokine gene expression involves differential activation of Rel A and NF-kappa B1.
Respiratory syncytial virus (RSV) infection of airway epithelial cells stimulates the expression and secretion of a variety of cytokines including the chemotactic cytokines interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and RANTES (regulated upon activation, normal T cell expressed and secreted). Chemokines are important chemoattractants for the recruitment of distinct sets of leukocytes to airway sites of inflammation. We have shown previously that chemokine expression is regulated in airway epithelial cells (A549) in a stimulus-specific manner in part through the redox-responsive transcription factors AP-1 and NF-kappaB. In this study, we examined the NF-kappaB-mediated effects of RSV and the proinflammatory cytokine TNFalpha on the induction of IL-8, MCP-1 and RANTES chemokine gene expression in A549 epithelial cells. The results demonstrate that RSV induces chemokine expression with distinct kinetics that is associated with a specific pattern of NF-kappaB binding activity. This distinction was further demonstrated by the differential effects of the NF-kappaB inhibitors dexamethasone (DEX) and N-acetyl-L-cysteine (NAC). NAC preferentially inhibited RSV induced chemokine expression, whereas DEX preferentially inhibited TNFalpha induced chemokine expression. DNA binding studies using NF-kappaB subunit specific binding ELISA demonstrated that RSV and TNFalpha induced different NF-kappaB binding complexes containing Rel A (p65) and NF-kappaB1 (p50). Both TNFalpha and RSV strongly induced Rel A the activation subunit of NF-kappaB, whereas only TNFalpha was able to substantially induce the p50 subunit. Consistent with the expression studies, RSV but not TNFalpha induction of Rel A and p50 were markedly inhibited by NAC, providing a mechanism by which TNFalpha and RSV can differentially activate chemokine gene expression via NF-kappaB. These data suggest that RSV induction of chemokine gene expression, in contrast to TNFalpha, involves redox-sensitive NF-kappaB complexes containing predominantly Rel A.


Neuromagnetic evidence of broader auditory cortical tuning in schizophrenia.
Deficits in basic auditory perception have been described in schizophrenia. Previous electrophysiological imaging research has documented a structure-function disassociation in the auditory system and altered tonotopic mapping in schizophrenia. The present study examined auditory cortical tuning in patients with schizophrenia. Eighteen patients with schizophrenia and 15 comparison subjects were recorded in a magnetoencephalographic (MEG) experiment of auditory tuning. Auditory cortical tuning at 1 kHz was examined by delivering 1 kHz pure tones in conjunction with pure tones at 5 frequencies surrounding and including 1 kHz. Source reconstruction data were examined for evidence of frequency specificity for the M100 component. There was a significant broadening of tuning in the schizophrenia group evident for the source amplitude of the M100. The frequently reported reduction in anterior-posterior source asymmetry for individuals with schizophrenia was replicated in this experiment. No relationships between symptom severity ratings and MEG measures were observed. This finding suggests that the frequency specificity of the M100 auditory evoked field is disturbed in schizophrenia, and may help explain the relatively poor behavioral performance of schizophrenia patients on simple frequency discrimination tasks.


Comparison of gemcitabine and anthracycline antibiotics in prevention of superficial bladder cancer recurrence.
Because of the failure, shortage and related toxicities of Bacillus Calmette-Guérin (BCG), the other intravesical chemotherapy drugs are also widely used in clinical application. Gemcitabine and anthracycline antibiotics (epirubicin and pirarubicin) are widely used as first-line or salvage therapy, but which drug is better is less discussed. A total of 124 primary NMIBC patients administered intravesical therapy after transurethral resection of bladder tumor (TURBT) at Nanjing Drum Tower hospital from January 1996 to July 2018. After TURBT, all patients accepted standard intravesical chemotherapy. Recurrence was defined as the occurrence of a new tumor in the bladder. Progression was defined as confirmed tumor invading muscular layer. Treatment failure was defined as need for radical cystectomy (RC), systemic chemotherapy and radiation therapy. Of the 124 patients who underwent intravesical chemotherapy, 84 patients were given gemcitabine, 40 patients were given epirubicin or pirarubicin, with mean follow-up times (mean ± SD) of (34.8 ± 17.9) and (35.9 ± 22.1) months respectively. The clinical and pathological features of patients show no difference between two groups. Recurrence rate of patients given gemcitabine was 8.33% (7 out of 84), the recurrence rate was 45% (18 out of 40) for epirubicin or pirarubicin (P < 0.0001). The progression rates of gemcitabine, anthracycline antibiotics groups were 2.38% (2 out of 84) and 20% (8 out of 40), respectively (P < 0.001). The rate of treatment failure is 8.33% (7 out of 84) and 25% (10 out of 40), respectively (P = 0.012). Gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence (HR = 0.165, 95% CI 0.069-0.397, P = 0.000), progression (HR = 0.160, 95% CI 0.032-0.799, P = 0.026) and treatment failure (HR = 0.260, 95% CI 0.078-0.867, P = 0.028). In conclusion, gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence, progression and treatment failure. Gemcitabine could be considered as a choice for these patients who are not suitable for BCG.


Physical and functional interactions between nuclear receptor LXRα and the forkhead box transcription factor FOXA2 regulate the response of the human lipoprotein lipase gene to oxysterols in hepatic cells.
Lipoprotein lipase (LPL) catalyzes the hydrolysis of triglycerides from triglyceride-rich lipoproteins such as VLDL and chylomicrons in the circulation. Mutations in LPL or its activator apolipoprotein C-II cause hypertriglyceridemia in humans and animal models. The levels of LPL in the liver are low but they can be strongly induced by a high cholesterol diet or by synthetic ligands of Liver X Receptors (LXRs). However, the mechanism by which LXRs activate the human LPL gene is unknown. In the present study we show that LXR agonists increased the mRNA and protein levels as well as the promoter activity of human LPL in HepG2 cells. A promoter deletion analysis defined the proximal -109/-28 region, which contains a functional FOXA2 element, as essential for transactivation by ligand-activated LXRα/RXRα heterodimers. Silencing of endogenous FOXA2 in HepG2 cells by siRNAs or by treatment with insulin compromised the induction of the LPL gene by LXR agonists whereas mutations in the FOXA2 site abolished the synergistic transactivation of the LPL promoter by LXRα/RXRα and FOXA2. Physical and functional interactions between LXRα and FOXA2 were established in vitro and ex vivo. In summary, the present study revealed a novel mechanism of human LPL gene induction by oxysterols in the liver with is based on physical and functional interactions between transcription factors LXRα and FOXA2. This mechanism, which may not be restricted to the LPL gene, is critically important for a better understanding of the regulation of cholesterol and triglyceride metabolism in the liver under healthy or pathological states.


(R(p))-2-Isopropyl-5-methyl-cyclo-hexyl isoprop-yl(phen-yl)phosphinate.
The title compound, C(19)H(31)O(2)P, features a distorted tetra-hedral P atom that bonds to the phenyl ring, isopropyl and 2-isopropyl-5-methyl-cyclo-hexyl groups, and is determined as having an R(p) configuration. A chair conformation is observed for the cyclo-hexyl ring. In the crystal, mol-ecules are linked into chains running along the a axis by weak inter-molecular C-H⋯O hodrogen bonds.


Intraocular pressure seven years after extracapsular cataract extraction and sulcus implantation of a posterior chamber intraocular lens.
Seven years after extracapsular cataract extraction (ECCE) and sulcus implantation of a posterior chamber intraocular lens, we measured the intraocular pressure (IOP) in 28 eyes of 28 patients. The results were compared with the preoperative IOP and with the postoperative IOP at four months and 2 1/2 years. The mean IOP value seven years after surgery was 1.3 mm Hg lower than the preoperative mean value. No significant difference was found among the values at four months, 2 1/2 years, and seven years. One patient experienced a marked rise in IOP between 2 1/2 years and seven years and was excluded from the calculations. However, we could not tell whether it was a consequence of the cataract surgery. In this study, we found that IOP stabilized at a postoperative level that was significantly lower than the preoperative value and has remained there for seven years.


Mutagenesis of kiwifruit CENTRORADIALIS-like genes transforms a climbing woody perennial with long juvenility and axillary flowering into a compact plant with rapid terminal flowering.
Annualization of woody perennials has the potential to revolutionize the breeding and production of fruit crops and rapidly improve horticultural species. Kiwifruit (Actinidia chinensis) is a recently domesticated fruit crop with a short history of breeding and tremendous potential for improvement. Previously, multiple kiwifruit CENTRORADIALIS (CEN)-like genes have been identified as potential repressors of flowering. In this study, CRISPR/Cas9- mediated manipulation enabled functional analysis of kiwifruit CEN-like genes AcCEN4 and AcCEN. Mutation of these genes transformed a climbing woody perennial, which develops axillary inflorescences after many years of juvenility, into a compact plant with rapid terminal flower and fruit development. The number of affected genes and alleles and severity of detected mutations correlated with the precocity and change in plant stature, suggesting that a bi-allelic mutation of either AcCEN4 or AcCEN may be sufficient for early flowering, whereas mutations affecting both genes further contributed to precocity and enhanced the compact growth habit. CRISPR/Cas9-mediated mutagenesis of AcCEN4 and AcCEN may be a valuable means to engineer Actinidia amenable for accelerated breeding, indoor farming and cultivation as an annual crop.


Brain evolution: when is a group not a group?
In testing the 'social brain hypothesis' with comparative data, most research has used group size as an index of cognitive challenge. Recent work suggests that this measure is too crude to apply to a wide range of species, and biologists may need to develop other ways of extending these analyses.


Endovascular aortic arch repair with a pre-cannulated double-fenestrated physician-modified stent graft: a benchtop experiment.
The critical step in total endovascular aortic arch repair is to ensure alignment of fenestrations with, and thus maintenance of flow to, supra-aortic trunks. This experimental study evaluates the feasibility and accuracy of a double-fenestrated physician-modified endovascular graft [single common large fenestration for the brachiocephalic trunk and left common carotid artery and a distal small fenestration for left subclavian artery (LSA) with a preloaded guidewire for the LSA] for total endovascular aortic arch repair. Eight fresh human cadaveric thoracic aortas were harvested. Thoracic endografts with a physician-modified double fenestration were deployed for total endovascular aortic arch repair in a bench test model. A guidewire was preloaded through the distal fenestration for the LSA. All experiments were undertaken in a hybrid room under fluoroscopic guidance with subsequent angioscopy and open evaluation for assessment. Mean aortic diameter in zone 0 was 31.3 ± 3.33 mm. Mean duration for stent graft modification was 20.1 ± 5.8 min. Mean duration of the procedure was 24 ± 8.6 min. The Medtronic Valiant Captivia stent graft was used in 6 and the Cook Alpha Zenith thoracic stent graft in 2 cases. LSA catheterization was technically successful with supra-aortic trunk patency in 100% of cases. The use of a double-fenestrated stent graft with a preloaded guidewire appears to be a useful technical addition to facilitate easy and correct alignment of stent graft fenestrations with supra-aortic trunk origins.