Systematic identification of shikonins and shikonofurans in medicinal Zicao species using ultra-high performance liquid chromatography quadrupole time of flight tandem mass spectrometry combined with a data mining strategy.
Shikonin, shikonofuran and their derivatives are the main bioactive components of Zicao, a traditional Chinese herbal medicine prepared with the dried roots of Lithospermum erythrorhizon, Arnebia euchroma or Arnebia guttata. However, approaches on the systematic discovery and identification of shikonins and shikonofurans, especially unknown ones, are still not available. To address this issue, the gas-phase CID-fragmentation routes for the shikonins and shikonofurans were established by using ESI-QTOF-MS in the negative ion mode and low-energy collision induced dissociation tandem mass spectrometry (CID-MS/MS) in this study using seventeen standards. As a result, diagnostic product ions for rapid discovery and classification of shikonins and shikonofurans were determined. In addition, various mobile phase compositions and UHPLC elution programs were evaluated to achieve optimal separation efficiency and detection response of these types of analytes. Based on these findings, an integral approach using UHPLC-ESI-QTOF-MS and CID-MS/MS analyses together with a novel two steps data mining strategy was developed for systematic analysis of shikonins and shikonofurans in complex samples. Consequently, 58 compounds including 32 novel ones were efficiently discovered and identified from the crude extract of Zicao. Moreover, comparative analyses of the 58 chemical components in three Zicao species including Lithospermum erythrorhizon, Arnebia euchroma and Arnebia guttata samples were conducted using the established analytical method, which can be instructive for future utilization of Zicao and its related medicinal products.


Genotyping by allele-specific L-DNA-tagged PCR.
We have developed a novel method for typing single-nucleotide polymorphisms (SNPs) that can be applicable to rapid screening. The method involves the fusion of two PCR techniques, allele-specific PCR (AS-PCR) and L-DNA-tagged PCR (LT-PCR), which enables us to label PCR products with sequence-defined tags of mirror-image DNA (L-DNA). PCR products were applied without any purification or denaturation steps to gold surfaces where complementary single-stranded L-DNA was immobilized, and the products were detected with surface plasmon resonance (SPR) imaging. We were able to clearly discriminate 3 genotypes at position 2677 of the MDR1 gene (G/G-homozygote, G/T-heterozygote, and T/T-homozygote) by comparing SPR difference images.


Review of the Salmonella typhimurium mutagenicity of benzidine, benzidine analogues, and benzidine-based dyes.
We have reviewed the mutagenicity of benzidine analogues (including benzidine-based dyes), with a primary emphasis on evaluating results of the Salmonella/microsome mutagenicity assay. Many of these amines are mutagenic in tester strains TA98 and TA100 but require exogenous mammalian activation (S9) for activity. A few amines with halogen or nitro-groups in the structure are direct-acting mutagens. The addition of a sulfonic acid moiety to the molecule of benzidine reduced the mutagenicity of benzidine; whereas, methoxy, chloro, or methyl group additions did not. Complexation with a metal ion also decreased the mutagenicity. A substitution of an alkyl group on the ortho position next to an amine group also influenced the mutagenicity. Most carcinogenic benzidine analogues are mutagenic, and their metabolism to electrophiles that interact with DNA, leading to mutations, plays a central role in their carcinogenesis.


Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration.
A critical target in age-related macular degeneration (AMD) is the retinal pigment epithelium (RPE), which forms the outer blood-retina barrier (BRB). RPE-barrier dysfunction might result from the disruption of intercellular tight junctions (TJs). A Connexin43 (Cx43)-based peptide, aCT1, has been shown to prevent VEGF-induced loss of transepithelial resistance, choroidal neovascularization (CNV) and RPE-cell damage via the stabilization of TJs. Here, we probe the relative efficacies of aCT1 alone, anti-VEGF alone, and aCT1 with anti-VEGF in treating AMD pathologies. aCT1 monotherapy administered as topical eye drops with and without a VEGF blocking antibody administered systemically was tested in a mouse model of laser-induced CNV. The CNV mouse is the standard neovascular AMD model, reproducing hallmarks of its pathology. CNV lesion size and fluid accumulation were assessed using optical coherence tomography. During the angiogenesis phase of CNV lesion development, single applications of anti-VEGF or aCT1 reduced lesion and fluid dome size equally. The combinatorial aCT1/anti-VEGF strategy demonstrated lack of additive effects in this model. These data suggest that TJ stabilization by aCT1 is effective in ameliorating RPE dysfunction in a model of AMD-like angiogenesis, and that this strategy is as effective as the current clinical standard of care, anti-VEGF therapy. Critically, aCT1 holds potential as a new neovascular AMD treatment that can be administered using eye drops, which is preferable to the intravitreal injections required for standard anti-VEGF therapy.


Stick with the nose…Saliva rapid antigen testing is not a viable method for testing children under 5 years old.
Respiratory testing with rapid antigen tests (RATs) in children under 5 years of age may be uncomfortable and presents specific challenges to testing due to compliance and procedural distress. The aim of this study was to investigate sensitivity and feasibility of self-collected nasal and saliva RAT tests compared with a combined nose and throat (CTN) swab PCR in children under 5. Children aged between 1 month and 5 years, with confirmed COVID-19 or who were a household contact within 7 days were included. A saliva RAT, nasal RAT and CTN swab were collected by the parent. SARS-CoV-2 cycle threshold (Ct) values for CTN tested by PCR were compared with saliva and nasal RAT results. Parent preference for method of sample was recorded. Forty-one children were recruited with median age of 1.5 (interquartile range 0.7-4.0) years. Only 22/41 (54%) of parents were able to successfully collect a saliva RAT from their child. Sensitivity of the nasal RAT and saliva RAT was 0.889 (95% confidence interval (CI) 0.739-0.969) and 0.158 (95% CI 0.034-0.396), respectively. Upper limit of nasal RAT detection by CTN Ct value was higher than saliva (36.05 vs. 27.29). While saliva RAT was rated most comfortable, nasal RAT was rated the preferred specimen by parents for future testing, due to saliva collection difficulties and time taken. Rapid antigen testing with nasal RAT is a more feasible and sensitive method for SARS-CoV-2 detection in young children compared with saliva RAT.


Impact of limb length discrepancy on functional outcome in total knee arthroplasty patients: a prospective cohort study.
Limb length alteration following total knee arthroplasty (TKA) has been under-reported. Few studies have shown a significant association between limb length discrepancy (LLD) and poor functional outcome. This prospective study evaluated the impact of radiographic and perceived LLD on functional outcome in TKA. The variables affecting LLD were also evaluated. The preoperative and postoperative limb lengths of TKA patients (112 knees, 81 patients, KL grade ≥ 3) were measured in full-length digital radiographs. The Hip-Knee-Ankle (HKA) angles were also measured. The functional outcome (Western Ontario and McMaster Universities Arthritis Index) and perception about LLD were evaluated after six months. The mean preoperative radiographic LLD in the unilateral and bilateral TKA groups was 0.75 cm ± 0.60 cm and 0.58 cm ± 0.52 cm (P = 0.197), respectively. Similarly, postoperative LLD was 0.76 cm ± 0.85 cm in the unilateral group and was 0.59 cm ± 0.92 cm (P = 0.402) in the bilateral group. Only 19.7% of patients had postoperative radiographic LLD of ≥ 10 mm, and 80.2% of patients had LLD of < 10 mm. The functional outcome was significantly affected when LLD exceeded 10 mm (correlation coefficient 0.54, P < 0.001). Linear regression analysis revealed no significant effects of age, sex, height, weight, BMI, preoperative LLD and difference in deformity between the limbs on postoperative LLD. 34.5% of patients perceived LLD in the preoperative period, which decreased to 3.7% in the postoperative period. Perceived LLD did not correlate to radiographic LLD and functional outcome. There is no significant difference in radiographic LLD between unilateral and bilateral TKA. The functional outcome is adversely affected by radiographic LLD of ≥ 10 mm. Age, sex, BMI, preoperative LLD and difference in deformity angle do not affect the LLD. About one-third of patients perceive LLD in the preoperative period, which improves significantly after TKA. II.


Phase-Selective Synthesis of Mo-Ta-C Ternary Nanosheets by Precisely Tailoring Mo/Ta Atom Ratio on Liquid Copper.
Phase-selective synthesis is an effective way to expand the ultra-thin transition metal carbide family and tune its properties. Herein, a chemical vapor deposition route with specially designed substrate (Ta wire-Cu foil-Mo foil) is carried out to synthesize Mo-Ta-C ternary nanosheets with tunable phase structure. The Ta atoms diffuse on the surface of liquid copper and Mo atoms diffuse through the liquid copper to the surface, which react with the carbon atoms decomposed from the methane and form the Mo-Ta-C ternary nanosheets. By precisely tailoring the Mo/Ta ratio and growth temperature, ultrathin layered orthorhombic (Mo2/3Ta1/3)2C nanosheets and non-layered cubic (Mo0.13Ta0.87) C nanosheets with thickness of 21 and 4 nm are selectively synthesized. The approach could pave the way for the formation of multi-component carbide nanosheets with controllable phases.


Factors influencing seed germination of medicinal plant Salvia aegyptiaca L. (Lamiaceae).
Salvia aegyptiaca is a xerophytic perennial herb belongs to the Lamiaceae family commonly used for medicinal purposes. Laboratory experiments were carried out to assess the effects of temperature and salinity on seed germination and recovery responses after transferring to distilled water. Temperatures between 10 and 40 °C seem to be favourable for the germination of this species. Germination was inhibited by either an increase or decrease in temperature from the optimum (30 °C). The highest germination percentages were obtained at 0 mM NaCl; however, the increase of solution osmolalities progressively inhibited seed germination. The germination rate decreased with an increase in salinity for most of tested temperatures, but comparatively higher rates were obtained at 30 °C. Salt stress decreased both the percentage and the rate of germination. An interaction between salinity and temperature yielded no germination at 300 mM NaCl. By experimental transfer to distilled water, S. aegyptiaca seeds that were exposed to moderately saline conditions recovered and keep their ability to germinate mostly at low temperatures. At 300 mM NaCl, germination recovery decreased with increasing temperature and it was completely inhibited at 40 °C.


Old and new pathways of protein export in chloroplasts and bacteria.
Targeting of chloroplast proteins to the thylakoid membrane is analogous to bacterial secretion, and much of what we know has been learned from secretory mechanisms in Escherichia coli. However, chloroplasts also use a delta pH-dependent pathway to target thylakoid proteins, at least some of which are folded before transport. Previously, this pathway seemed to have no cognate in bacteria, but recent results have shown that the HCF106 gene in maize encodes a component of this pathway and has bacterial homologues. This delta pH-dependent pathway might be an ancient conserved mechanism for protein translocation that evolved before the endosymbiotic origin of plastids and mitochondria.


Factors affecting breast-feeding practice among a sample of Iranian women: a structural equation modeling approach.
Breastfeeding is one of the most sensitive stages in the development of children, having many benefits for the mother and the child. The present study aimed to determine factors associated with breastfeeding intention and behavior in mothers living in Taft County, Iran. In this cross-sectional design, the statistical population consisted of 420 mothers with infants under 1 year of age living in Taft County of Yazd province, Iran. The research data were collected from health records of infants under one in health centers of the county as well as a researcher-made questionnaire including demographic information, knowledge and attitude towards breastfeeding, social support and perceived self-efficacy, and breastfeeding intention and behavior. Structural Equation Modeling (SEM) based on AMOS 18 were employed to analyze the relationship between research variables. The mean age of mothers was 28.04 ± 6.49 year and the children were 10 ± 6 months. Half of the mothers (50.3%) had cesarean sections and more than half (55.8%) of the children were males. Mothers' attitude (β = 0.442; 95% CI: 0.284, 0.599), self-efficacy (β = 0.186; 95% CI: 0.047, 0.324) and perceived social support (β = 0.178; 95% CI: 0.035, 0.322) were respectively the strongest predictors of breastfeeding intention. Besides, the breastfeeding intention affected breastfeeding behavior with a high coefficient (0.857; 95% CI: 0.735, 0.979). The study provided informative pathways on the association of maternal attitude, social support and self-efficacy with breast feeding behavior. These findings could be useful for designing health education and promotion programs about breast feeding among women.


A multicenter study using positive deviance for improving hand hygiene compliance.
Positive deviance (PD) can be a strategy for the improvement of hand hygiene (HH) compliance. This study was conducted in 8 intensive care units and 1 ward at 7 tertiary care, private, and public hospitals. Phase 1 was a 3-month baseline period (from August to October 2011) in which HH counts were performed by observers using iPods (iScrub program). From November 2011 to July 2012, phase 2, a PD intervention was performed in all the participating centers. We evaluated the consumption of HH products (alcohol gel and chlorhexidine) and the incidence density of health care-associated infections. There was a total of 5,791 HH observations in the preintervention phase and 11,724 HH observations in the intervention phase (PD). A statistically significant difference was found in overall HH compliance with 46.5% in the preintervention phase and 62.0% in the PD phase (P < .001). There was a statistically significant reduction in the incidence of density of device-associated infections per 1,000 patient-days and also in the median of length of stay between the preintervention phase and the PD phase (13.2 vs 7.5 per 1,000 patient-days, respectively, P = .039; and 11.0 vs 6.8 days, respectively, P < .001, respectively). PD demonstrated great promise for improving HH in multiple inpatient settings and was associated with a decrease in the median length of stay and the incidence of device-associated HAIs.


The pathology of encephalic arteriovenous malformations treated by prior embolotherapy.
A pathologic study was undertaken of seven encephalic arteriovenous malformations, including five resected from one to seven days after balloon embolization, one resected 10 days after embolization with polyvinyl alcohol foam (PVA), and a large mesencephalic AVM in a patient who died eight weeks after a series of embolization procedures with PVA and silicone spheres. AVM's resected 6-7 days following balloon embolization showed focal mural and adventitial inflammatory infiltrates and parenchymal (i.e. non-vascular) necrosis of a large portion of one AVM. The AVM examined 7 days post-balloon embolization showed an intraluminal thrombus containing refractile particles surrounded by foreign body giant cells (FBGC's). The AVM removed 10 days after PVA embolotherapy showed mural and perivascular necrosis with infiltration by polymorphonuclear leukocytes. The single autopsy case showed FBGC's surrounding residual PVA, refractile particles deep within vascular walls, and marked mural thickening of AVM channel walls, changes that may represent a response to previous angionecrosis and inflammation at the time of embolization. These findings, the pathogenesis of which is discussed in detail, may help to explain some of the rare complications of iatrogenic embolotherapy with these materials, as well as providing evidence for the basis of their efficacy.


Cassia sieberiana DC. leaves modulate LPS-induced inflammatory response in THP-1 cells and inhibit eicosanoid-metabolizing enzymes.
According to ethnobotanical surveys, Cassia sieberiana DC. (1825) is a particularly reputed species in African folk Medicine, namely due to the application of its leaves and roots for the treatment of diseases and symptomatology that appear to be related with an inflammatory background. In contrast with the roots of the plant, the leaves remain to be investigated, which prompted us to further detail mechanisms underlying their anti-inflammatory properties, by using in vitro models of disease. Considering its use in the amelioration and treatment of conditions that frequently underlie an inflammatory response, C. sieberiana leaves extract was prioritized amongst a collection of extracts obtained from plants collected in Guinea-Bissau. As such, this work aims to deliver experimental data on the anti-inflammatory properties of C. sieberiana leaf and to establish possible associations with its chemical composition, thus providing a rationale on its use in folk Medicine. The chemical profile of an hydroethanol extract obtained from the leaves of the plant was established by HPLC-DAD-ESI/MSn in order to identify bioactives. The extract and its main compound were tested towards a series of inflammatory mediators, both in enzymatic and cell-based models. The capacity to interfere with the eicosanoid-metabolizing enzymes 5-lipoxygenase (5-LOX), cyclooxygenase-1 (COX-1) and -2 (COX-2) was evaluated in cell-free systems, while the effects in interleukin 6 (IL-6) and tumour necrosis factor-α (TNF-α) levels produced by THP-1 derived macrophages were assessed through ELISA. HPLC-DAD-ESI/MSn analysis of the extract elucidated a chemical profile qualitatively characterized by a series of anthraquinones, particularly rhein derivatives, and nine flavonols, most of which 3-O-glycosylated. Considering the concentrations of the identified compounds, quercetin was detached as the main component. Effects of the hydroethanol extract obtained from C. sieberiana leaves against key enzymes of the arachidonic acid cascade were recorded, namely a concentration-dependent inhibition against 5-LOX, at concentrations ranging from 16 to 250 μg mL-1 and a selective inhibitory action upon COX-2 (IC50 = 3.58 μg mL-1) in comparison with the isoform COX-1 (IC50 = 9.10 μg mL-1). Impact on inflammatory cytokines was also noted, C. sieberiana leaf extract significantly decreasing IL-6 levels in THP-1 derived macrophages at 250 and 500 μg mL-1. In contrast, TNF-α levels were found to be increased in the same model. Quercetin appears to partially account for the observed effects, namely due to the significant inhibitory effects on the activity of the arachidonic acid metabolizing enzymes COX-2 and 5-LOX. The anti-inflammatory effects herein reported provide a rationale for the use of C. sieberiana leaves in African folk practices, such as in the treatment of arthritis, rheumatism and body aches. Considering the occurrence of flavonoidic and anthraquinonic constituents, as well as the observed anti-inflammatory properties of quercetin, recorded effects must be related with the presence of several bioactives.


Expression of engineered antibodies in plants: a possible tool for spiroplasma and phytoplasma disease control.
ABSTRACT In an attempt to develop maize plants with resistance to corn stunt spi-roplasma (CSS), a single-chain Fv fragment (scFv) gene that was constructed from antibodies with strong inhibitory activity against CSS, was expressed in a cell line of maize. However, plants regenerated from this transgenic cell line showed no distinct resistance to CSS infection under the greenhouse conditions. The affinity and functionality of scFv in vivo and the locations of CSS and expressed scFv in maize could be a part of the contributing factors affecting this result. Progress of expressing antibodies in plants for plant pathogen resistance is also discussed.


Interface between energy consumption, CO2 emissions, economic growth, and macroeconomic openness in financial action task force countries through the lens of a causality approach.
There is strong scientific evidence to suggest that carbon dioxide (CO2) emissions are one of the key drivers of global warming. Rising CO2 emissions across the globe have been traced back to increasing global trade and rapid industrial development powered by fossil fuels. High CO2 emissions have had an adverse effect on the quality of life and economic growth of communities across the globe. In this study, the Granger causality approach is used to examine scientifically some causal relationships between energy consumption, CO2 emissions, economic growth, and key macroeconomic variables (trade openness and foreign direct investment) in the panel of Financial Action Task Force (FATF) countries. FATF countries are signatories to agreements to adhere to good financial practices to ensure sustainable development of their economies. The empirical analysis was conducted for the period 1980 to 2020. Results indicate a strong endogenous relationship between the variables in the short and long run. The analysis suggests that careful co-curation of economic, trade, energy, foreign direct investment, and environmental management policies is needed to ensure sustainable economic development in the FATF countries. Global trade and foreign direct investment policies must foster new environmental-friendly industries and greater use of clean renewable energy among these countries. Note: Arrows indicate direction of possible causal links between the variables.


Factors influencing the outcome of deep infection following total knee arthroplasty.
Whereas clinical studies have revealed a number of important risk factors for postoperative infection following total knee arthroplasty (TKA), it is unclear which factor influences clinical results. A multicenter study was therefore performed by reviewing 51 patients with deep infection after TKA and seeking for the factors related to clinical outcomes. Fifty-one deep infections after TKA were treated from 2000 to 2011 at the multicenter including a university or three arthroplasty centers. Among them, two clinical outcome measures including retention of prosthesis at initial treatment and functional prosthetic knee were assessed for several factors such as age, sex, primary diagnosis, onset time after primary TKA, type of hospital where the primary TKA was performed and the organism's resistance to methicillin using the logistic regression analysis model. Among the factors, type of hospital where the primary TKA was performed and onset time after primary TKA had higher multivariable-adjusted odds ratios (ORs) for retention of primary prosthesis (ORs 35.21 and 11.69, respectively.). The cases which primary surgery were performed in arthroplasty centers had higher multivariable-adjusted ORs for functional prosthetic knee (OR 4.9). Thirty-one infection cases with non-methicillin-resistant organisms were all able to keep functional prosthetic knee after the operation, whereas 13 out of 20 infection cases with methicillin-resistant organisms lost their knee function after the operation. Onset time after primary TKA, type of hospital where the primary surgery was performed and the organism's resistance to methicillin are important factors influencing the clinical outcomes after infected TKA. Level 3. Retrospective comparative study.


Costs and trade-offs of grazer-induced defenses in Scenedesmus under deficient resource.
The green alga Scenedesmus obliquus can form inducible defensive morphs under grazing threat. Costs and trade-offs of inducible defense are expected to accompany the benefits of defensive morphs, but are hard to detect under nutrient-sufficient experimental conditions. To test the existence of costs associated with inducible defense, we cultured S. obliquus along resource availability gradients in the presence or absence of infochemical cues from Daphnia, and measured the strength of defensive colony formation and fitness characters. Under the lowest phosphorous concentration, the expression of inducible defensive colony resulted in decreased growth rate, which provides direct evidence for physiological costs. Along the gradient reduction of phosphorous concentration or light intensity, inducible defense in S. obliquus showed a decreasing trend. However, the photosynthetic efficiency of S. obliquus was barely affected by its defense responses, suggesting that the negative correlations between resource availability and colony formation of this alga may be due to resource-based trade-offs in the allocation of limited resources. Thus, our results indicated that expression of inducible defense of S. obliquus was impaired under insufficient phosphorus or light. Furthermore, under severe phosphate deficiency, obvious physiological costs of inducible defense could be detected even though defensive colony formation also decreased significantly.


Zinner syndrome: A first case report from Ethiopia.
A triad of unilateral renal agenesis, ipsilateral seminal vesicle cyst and ipsilateral ejaculatory duct obstruction has been called Zinner syndrome since its first description in 1914 by Zinner. It is a very rare congenital abnormality of the male genitourinary tract due to abnormal embryologic development of the Wolffian ducts. There have been several case reports from different parts of the world about the clinical and imaging findings of these anomaly. In this case report, we present the first case report of Zinner syndrome in a 28-year-old male Ethiopian patient.


Genome-wide identification, characterization and expression analysis of non-RD receptor like kinase gene family under Colletotrichum truncatum stress conditions in hot pepper.
Receptor like kinases (RLKs) are preserved upstream signaling molecules which regulate several biological processes from plant development to various stress adaptation programs. Non arginine aspartate (non-RD) a prominent class of RLKs plays a significant role in disease resistance and apoptosis in plants. In present investigation, a comprehensive in silico analysis for non-RD Kinase gene family as well as identification of gene structures, sequence similarity, chromosomal localization, gene duplication analysis, promoter analysis, transcript expression profiles and phylogenic studies were done. In this study, twenty-six genes were observed on nine out of twelve chromosomes. All these genes were clustered into five subfamilies under large monophyletic group termed as Interleukin-1 Receptor-Associated Kinase (IRAK) family. Some of the important physiochemical properties of twenty-six proteins are determined and ranged in the following order: (a) Amino acids size ranged from (620 to 1781) (b) Molecular weight ranged as of (70.11 to 197.11 KDa) and (c) Theoretical PI ranged from (5.69 to 8.63) respectively. Structural diversity in genomic structure among non-RD kinase gene family was identified and presence of pathogen induced cis regulatory elements including STRE, MYC, MYB, and W box were found. Expression profiles revealed the potential ability of three genes CaRLK1 from LRRXII and CaRLK15,16 from stress antifung subfamily were pointedly upregulated beyond the severe stress time period (9 DAI) in anthracnose resistant genotype PBC-80 in response to Colletotrichum truncatum infection. Subsequently, in silico studies from the available genome sequencing data helped us to identify candidate genes tangled in inducing disease resistance.


Cluster of climatic and pollutant characteristics increases admissions for acute myocardial infarction: Analysis of 30,423 patients in the metropolitan area of Sao Paulo.
The impact of simultaneous adverse climate conditions in the risk of myocardial infarction (MI) was not tested before. The aim of the present study was to investigate the impact of the combination of climate and air pollution features in the number of admissions and mortality due to acute myocardial infarction in 39 municipalities of São Paulo from 2012 to 2015. Data about MI admissions were obtained from the Brazilian public health system (DataSUS). Daily information on weather were accessed from the Meteorological Database for Teaching and Research. Additionally, daily information on air pollution were obtained from the Environmental Company of the State of São Paulo. A hierarchical cluster analysis was applied for temperature, rainfall patterns, relative air humidity, nitrogen dioxide, particulate matter 2.5 and particulate matter 10. MI admissions and in-hospital mortality were compared among the clusters. Data analysis produced 3 clusters: High temperature variation-Low humidity-high pollution (n=218 days); Intermediate temperature variation/high humidity/intermediate pollution (n=751 days) and low temperature variation/intermediate humidity-low pollution (n=123 days). All environmental variables were significantly different among clusters. The combination of high temperature variation, dry weather and high pollution resulted in a significant 9% increase in hospital admissions for MI [30.5 (IQR 25.0-36.0)]; patients/day; P<0.01). The differences in weather and pollution did not have impact on in-hospital mortality (P=0.88). The combination of atmospheric conditions with high temperature variation, lower temperature, dryer weather and increased inhalable particles was associated with a marked increase of hospital admissions due to MI.


Determination of 7-chloro-3-(4-methyl-1-piperazinyl)-4h-1,2,4-benzothiadiazine-1,1-dioxide (DU-717) in plasma using electron-capture gas chromatography.
A gas chromatographic method has been developed which enables accurate determination of a new antihypertensive agent, DU-717, in plasma. DU-717 is first extracted with ethyl acetate and, after a clean-up procedure, derivatized with peracetic acid followed by diazomethane to form 2-methyl DU-717 N-oxide (direct methylation leads to mixtures). The N-oxide is then pyrolyzed to 2-methyl DU-717 on a gas chromatograph equipped with electron-capture detection. Accurate determinations are possible over a concentration range from 10 to 150 ng/ml of DU-717 in plasma at a relative standard deviation of 6.2%. The minimum detectable concentration is 1 ng/ml. Plasma levels of DU-717 in spontaneously hypertensive and normotensive rats following single oral administrations (10 mg/kg) have also been determined.


Construction of ternary CuO/CuFe2O4/g-C3N4 composite and its enhanced photocatalytic degradation of tetracycline hydrochloride with persulfate under simulated sunlight.
In this study, a graphitic carbon nitride (g-C3N4) based ternary catalyst CuO/CuFe2O4/g-C3N4 (CCCN) is successfully prepared thorough calcination method. After confirming the structure and composition of CCCN, the as-synthesized composites are utilized to activate persulfate (PS) for the degradation of organic contaminant. While using tetracycline hydrochloride (TC) as pollutant surrogate, the effects of initial pH, PS and catalyst concentration on the degradation rate are systematically studied. Under the optimized reaction condition, CCCN/PS is able to give 99% degradation extent and 74% chemical oxygen demand removal in assistance of simulated solar light, both of which are apparently greater than that of either CuO/CuFe2O4 and pristine g-C3N4. The great improvement in degradation can be assignable to the effective separation of photoinduced carriers thanks to the integration between CuO/CuFe2O4 and g-C3N4, as well as the increased reaction sites given by the g-C3N4 substrate. Moreover, the scavenging trials imply that the major oxidative matters involved in the decomposition are hydroxyl radicals (•OH), superoxide radicals (•O2-) and photo-induced holes (h+).


Efficient palladium-catalyzed synthesis of 3-aryl-4-indolylmaleimides.
Improved palladium catalysts for the Suzuki coupling of 3-bromo-1-methyl-4-(2-methyl-3-indolyl)maleimide have been developed. The coupling of both aryl- and heteroarylboronic acids proceeds smoothly in good to excellent yields at low catalyst loading.


Evaluating Hearing Loss in Patients Undergoing Second Line Anti Tubercular Treatment.
To estimate the prevalence of Sensorineural hearing loss and evaluate the severity of hearing impairment in patients undergoing second line injectable antitubercular treatment. To study the effects of duration of treatment, dose schedule and demographic factors which aggravates anti TB drug induced ototoxicity. Design-prospective and retrospective study Setting-ENT & TB clinic at our hospital and TB Hospital of Subject-18-50 year age , diagnosed MDR or XDR TB Method-baseline puretone audiometry was done of all patients. all patients divided in 3 group depending on aminoacid (amikacin , kanamycin, capreomycin). Follow up PTA was done at 3rd month, 6th month and 6 month after stopping treatment 35.48% of Group 1 (kanamycin) patients show High frequency hearing loss and 16% of patient have both high and low frequency hearing loss High frequency hearing loss 21% of Group 2 (amikacin) patients show High frequency hearing loss and 5% of patient have both high and low frequency hearing loss 20% of Group 3 (capreomycin) patients show High frequency hearing loss with no patient resulted low frequency loss Patients treated FOR MDR-TB develop significant adverse effects. Clinicians must consider risk benefit analysis during treatment as ototoxicity of injectable aminoglycoside ATT is permanent. Early detection of hearing loss through pure tone audiometry helps preventing and progression of hearing loss without compromising the treatment.


Total hip replacement fifteen years after pelvic support osteotomy (PSO): a case report and review of the literature.
Treatment of chronic hip instability in children and young adults is challenging. Proximal femoral osteotomy had been suggested to provide pelvic stability and improved abductor function. Total hip replacement after pelvic support osteotomy can be challenging due to altered anatomy due to angulation of the proximal femur in both frontal and sagittal planes. This is a 29-year-old woman who had total hip replacement after pelvic support osteotomy. The patient had pelvic support at the age of 14 years. Pelvic support osteotomy delayed the need for total hip replacement for 15 years. Preoperative planning for total hip replacement with model was used for proper understanding of the anatomy of the proximal femur. Revision of femoral component was necessary due to penetration of the proximal femur. In conclusion, total hip replacement after pelvic support osteotomy is a technically demanding procedure, and careful attention to surgical details is necessary for successful outcome.


[Hematological and immunological properties of herring gull (Larus argentatus) nestlings experimentally infected with Diphyllobothrium dendriticum (Cestoda: Pseudophyllidae)].
The morphological structure of the blood in herring gull nestlings and their immune system response to experimental infection with tapeworm Diphyllobothrium dendriticum have been studied. The leukocyte reaction pattern and the dynamics of immunoglobulin synthesis and populations of immunocompetent cells in the blood of nestlings during early invasion indicated a short duration of the cellular immune response and an insignificant humoral immune response. A pronounced trend to decrease in the hemoglobin level in the blood of infected nestlings has been revealed and this reduction was in part compensated by intensified erythropoiesis. It is shown, that the changes in hematologic and immune responses of the obligate definitive host provide for the mutual host-parasite adaptation.


The Muscle Appearance Satisfaction Scale: A factorial analysis of validity and reliability for its use on adult Chinese male weightlifters.
Muscle dysmorphia (MD) is the distorted perception of men's own muscle appearance. The increasing popularity of weightlifting in Chinese men suggests the presence of MD. The study assessed the validity and reliability of the Muscle Appearance Satisfaction Scale (MASS) for its use on adult Chinese males. Exploratory and confirmatory factor analyses of responses from 225 and 592 participants confirmed the same five factors for the 17-item Chinese version as the original MASS (CFI=.931, RMSEA=.052). The internal consistency for all factors were acceptable (Cronbach's α=.636 to .737). Correlation levels of its subscales with converging measurements indicated that the revised MASS is effective in assessing MD in Chinese male weightlifters. Differences in the importance of the factors suggest an influence of Chinese culture in the symptoms of MD and the need of assessing the MASS with populations from distinct demographics in China and from different cultures.


Elements of the major myofibrillar binding peptide motif are present in the earliest of true muscle type creatine kinases.
Most vertebrates possess two genes for cytoplasmic creatine kinase (CK) coding for muscle (M-CK) and brain (B-CK) isoforms which assemble into homo-dimeric (MM, BB) and hetero-dimeric (MB) active enzymes. In mammals and birds, a significant fraction of MM-CK is bound to the myofibrillar M-line where it is thought to facilitate energy buffering and transport. Myofibrillar binding is mediated by major and minor lysine charge clamp motifs (K104/K115 [major] and K8/K24 [minor] in chicken M-CK) located in the N-terminal region [J. Cell Biol. 149 (2000) 1225]. We have obtained the cDNA and deduced amino acid sequences for cytoplasmic CKs from two hagfish, Myxine glutinosa and Eptatretus stoutii, non-vertebrate craniates, and the sequences for two cytoplasmic CKs from the lamprey Lampetra japonica, a jawless true vertebrate. All four cDNAs code for CKs consisting of approximately 380 residues. Phylogenetic analyses showed that the hagfish and lamprey CKs are coded for by genes which are clearly muscle type (M) creatine kinases. Two of these four M-CKs have the K104/K115-equivalent residues of the major myofibrillar binding region while the other two have the K115 equivalent but lack the corresponding K104 residue. All four M-CKs lack the K8/K24 equivalent elements of the minor myofibrillar binding region. Comparison of these sequences to corresponding sequences of cytoplasmic CKs from two protochordates (tunicate, amphioxus) and M- and B-CKs from true fish and above reveal a pattern of acquisition (and loss) of key lysine residues consistent with the physiological context in which these enzymes operate.


Derivation of Equine-Induced Pluripotent Stem Cell Lines Using a piggyBac Transposon Delivery System and Temporal Control of Transgene Expression.
The discovery of induced pluripotent stem cells (iPSCs) has had a transforming effect on our understanding of biology and has brought an enormous promise to regenerative medicine. It has opened up a magnitude of unprecedented possibilities to study disease processes in vitro, model them in animal systems, and develop patient-specific cell-based regenerative therapies. iPSCs derived from other than the human species will be instrumental for bringing these prospects to fruition by providing preclinical models and novel treatments for veterinary medicine. In this chapter, we describe the derivation of iPSCs from equine embryonic fibroblasts using a non-viral method developed in our laboratory and originally applied to the murine and human systems (Woltjen et al., Nature 458:766-770, 2009). We will detail the procedures involved and discuss potential pitfalls as well as elaborate on possible variations and future improvements of this technique.


An analysis of the competitiveness of the tourism industry in a context of economic recovery following the COVID19 pandemic.
Business activities within the tourism industry are especially suffering from the consequences of the COVID19 pandemic. Those countries whose economy depends largely on tourism will experience a troublesome situation for years to come. Their return to a normal situation will be conditioned by the competitiveness of their tourism sector. The study begins by pinpointing the countries that have been more hardly stricken by the pandemic and in which tourism accounts for a greater share of the GDP. A comparative analysis of the competitiveness of these countries with that of world-leading countries will be carried out so as to conclude which will face the recovery period in a more vulnerable situation. The measurement of tourism competitiveness will be supported by the creation of a synthetic indicator based on the P2 distance method. A group of 13 countries has been identified as the most vulnerable, and it is advisable to act urgently in the following areas: the promotion of cultural elements and the historical and artistic heritage, the protection of natural areas, the availability of information and communication technologies, the international openness of the destination, and the availability of transportation infrastructures and tourist services.


ROS-induced endothelial stress contributes to pulmonary fibrosis through pericytes and Wnt signaling.
Pulmonary fibrosis is a grave diagnosis with insidious progression, generally considered as a consequence of aberrant epithelial wound healing and excessive scarring. This process is commonly modeled in animals by local bleomycin administration, resulting in peribronchial inflammation and subsequent fibrosis. We have previously described initiation and early development of distal pulmonary fibrosis following repeated subcutaneous bleomycin injections (systemic administration). The aim of this study was to identify mechanisms for the development of pulmonary fibrosis, which we hypothesize is related to endothelial stress and activation. Bleomycin was administered subcutaneously 3 times/week during 0.33-4w, and parenchymal alterations were studied. In addition, we used microvascular endothelial cells to investigate effects of bleomycin in vitro. Our results confirmed that systemic administration of bleomycin exerts oxidative stress indicated by an increase in Sod1 at 0.33, 1, and 4w (P<0.05). Endothelial cells were activated (increased CD106 expression) from 1w and onwards (P<0.05), and p21 expression was increased 2-3 times throughout the study (P<0.05) as were the number of β-catenin-positive nuclei (P<0.001). Wnt3a was increased at 0.33, 1, and 4w (P<0.01) and Wnt5a from 1w and onwards (P<0.001). The present study suggests that bleomycin-induced reactive oxygen species (ROS) causes DNA stress affecting the endothelial niche, initiating repair processes including Wnt signaling. The repeated systemic administrations disrupt a normally fine-tuned balance in the Wnt signaling. In addition, pericyte differentiation was affected, which may have significant effects on fibrosis due to their ability to differentiate into myofibroblasts. We conclude that the endothelial niche may have an important role in the development of pulmonary fibrosis and warrants further investigations.


RNA specific molecules: cytotoxic plant alkaloid palmatine binds strongly to poly(A).
The cytotoxic plant alkaloid palmatine was found to bind strongly by partial intercalation to single stranded poly(A) structure with binding affinity (Ka) of (8.36+/-0.26) x 10(5) M(-1). The binding of palmatine was characterized to be exothermic and enthalpy driven with one palmatine for every two adenine residues. On the other hand, the binding to the double stranded poly(A) has been found to be significantly weak. This study identifies poly(A) as a potential bio-target for the alkaloid palmatine and its use as a lead compound in antitumor drug screening.


Proximal row carpectomy versus limited wrist arthrodesis for advanced Kienböck's disease.
The outcomes in 20 patients with advanced Kienböck's disease treated by proximal row carpectomy (seven patients) or limited wrist arthrodesis (13 patients) were reviewed retrospectively. Postoperatively, the results were more satisfactory in terms of wrist pain, the range of wrist flexion-extension, and grip strength following limited wrist arthrodesis than after proximal row carpectomy, although the differences were not statistically significant. We recommend scaphotrapeziotrapezoid arthrodesis in selected patients with advanced Kienböck's disease who have a fragmented lunate.


High matrix metalloproteinase-to-E-cadherin ratio measured by bicolor fluorescent in situ hybridization is associated with lymphangiogenesis and lymph node metastasis in prostate cancer.
The colorimetric in situ hybridization (CISH)-based matrix metalloproteinase (MMP)-to-E-cadherin (ECD) ratio (MER) has been revealed as an excellent marker for the disease stage in prostate cancer. The one aim of this study was investigating a new method for estimation of MER by bicolor fluorescent ISH (bicolor FISH) with a computerized fluorescence detector-based system. Another aim was examination of relation of MER by bicolor FISH with expression of vascular endothelial growth factor-C (VEGF-C). The bicolor FISH technique used cyanin 5 (cy5)-labeled MMP-2 and -9 probes, and a cyanin 3 (cy3)-labeled ECD probe on needle biopsy specimens from 67 prostate cancer cases. The ISH was followed by computerized detection of the signal intensities and cy5-to-cy3 ratios using a fluorescence detector. VEGF-C expression was examined using cy5-labeled VEGF-C by computerized detection. The bicolor FISH-based MER was well correlated with CISH-based MER (P < 0.0001). The bicolor FISH-based MER correlated with Gleason score and pathologic stage of the cases. VEGF-C mRNA expression was associated with the pathologic stage and maximum lymph vessel density (LVD). The LVD was associated with VEGF-C expression at the tumor area where the maximum MER was detected (P < 0.0001). The MER was correlated with the VEGF-C expression and LVD, indicating lymph node metastasis of prostate cancer. Therefore, this computer-assisted MER is a useful marker for preoperative prediction of disease stage, especially lymph node metastasis, of prostate cancer.


Vitamin E deficiency in the monkey. I. Muscular dystrophy, hematologic changes, and the excretion of urinary nitrogenous constituents.
Eight young rhesus monkeys were fed a purified diet devoid of vitamin E. After from 6 to 13 months of feeding, all the animals developed signs of vitamin E deficiency. The signs of vitamin E deficiency in the monkey include muscular dystrophy, elevated excretion of creatine, allantoin, and free amino acids and decreased excretion of creatinine. The vitamin E-deficient monkeys all developed anemia and granulocytosis. Anemia was the first sign of vitamin E deficiency which was observed. All of these signs of vitamin E deficiency were reversed by treatment with alpha-tocopherol.


The roentgenographic manifestations and clinical features of lumbar spinal stenosis with special emphasis on the superior articular process.
Sixty-three cases of surgically confirmed lumbar spinal stenosis were studied with regard to the clinical manifestations, routine spine films, and myelograms. The results are compared with the data in the literature. While our clinical and myelographic findings correspond in general with those published data, we have found important features of the superior articular process seen on routine anteroposterior roentgenograms which have not been described in the literature. Two illustrative cases are presented to demonstrate such features.


Physical Activity in Pregnancy Is Associated with Increased Flow-mediated Dilation.
To determine the role of moderate-to-vigorous physical activity (MVPA) and sedentary behavior in flow-mediated dilation (FMD) and glucose metabolism during late pregnancy. Seventy normotensive, euglycemic pregnant women (31.6 ± 2.9 yr) in their third trimester (28-39 wk) were recruited. After a fasted blood sample; FMD was measured (brachial artery Doppler ultrasonography, normalized for the shear stimulus [area under the curve]). Anterograde and retrograde shear rate were estimated. Physical activity (MVPA) and sedentary behavior were assessed via accelerometry for seven consecutive days (Actigraph wGT3X-BT). We categorized the women as active (>150 min·wk) or inactive (<150 min·wk) according to their accelerometry data. Data were corrected for age and gestational age. On average, women were sedentary 67.1% ± 8.2% of their waking hours. Active pregnant women (>150 min·wk MVPA, n = 32) engaged in 266.7 ± 99.3 min·wk MVPA, whereas inactive pregnant women (<150 min·wk MVPA, n = 38) engaged in 76.1 ± 42.5 min·wk MVPA. The FMD response (normalized to the magnitude of shear stress stimulus) was greater in active compared with inactive pregnant women (6.5 ± 4.4 a.u. vs 3.9 ± 3.5 a.u.; F = 4.619; P = 0.005). The MVPA in active pregnant women was inversely correlated with insulin concentrations (r = -0.556; P = 0.03). In inactive pregnant women, higher amounts of sedentary behavior were associated with lower amounts of retrograde shear rate (r = 0.504; P = 0.02), retrograde blood flow (r = 0.499; P = 0.02), and retrograde velocity (r = 0.508; P = 0.02) during baseline, but not correlated with the FMD response. Engaging in MVPA during pregnancy is associated with improved FMD and a lower insulin concentration. Sedentary behavior was not associated with FMD responses.


Altered ventral striatal activation during reward and punishment processing in premanifest Huntington's disease: a functional magnetic resonance study.
Recent research using various neuroimaging methods revealed the crucial role of the striatum concerning the neuropathology of Huntington's disease. Degenerative changes located in the basal ganglia are already observable in premanifest stages of Huntington's disease (pre-HD), i.e., before the onset of manifest motor symptoms. Although the impact of the striatum on reward and punishment processing is well-established in healthy subjects, these processes have not been investigated in manifest and premanifest HD subjects using functional magnetic resonance imaging (fMRI) so far. We used the Monetary Incentive Delay Task to investigate valence discrimination in terms of rewarding and punishing cues in 30 pre-HD and 15 healthy subjects. According to the probability of disease onset within the next 5 years, pre-HD subjects were categorized as either near to motor symptom onset (pre-HD(near); 9.9 [±2.91] years to onset) or far from manifest disease onset (pre-HD(far); 23.49 [±5.99] years to onset). Compared to pre-HD(far) and healthy subjects, pre-HD(near) subjects showed a disturbed neuronal differentiation between reward and control anticipation located in the left ventral striatum. In contrast to pre-HD(far) and healthy subjects, no significant ventral striatal discrimination between punishing and control cues was detected in pre-HD(near) subjects. In the present study, we demonstrated for the first time significant differences in valence discrimination in pre-HD(near) subjects compared to pre-HD(far) subjects and healthy controls. Altered reward and punishment processing could therefore reflect a motivational deficit that may contribute to the pathogenesis of Huntington's disease.


Gene cloning and characterization of a novel highly organic solvent tolerant lipase from Proteus sp. SW1 and its application for biodiesel production.
Proteus sp. SW1 was found to produce an extracellular solvent tolerant lipase. The gene, lipA, encoding a bacterial lipase, was cloned from total Proteus sp. SW1 DNA. lipA was predicted to encode a 287 amino acid protein of 31.2 kDa belonging to the Group I proteobacterial lipases. Purified His-tagged LipA exhibited optimal activity at pH 10.0 and 55°C. It was highly stable in organic solvents retaining 112% of its activity in 100% isopropanol after 24 h, and exhibited more than 200% of its initial activity upon exposure to 60% acetone, ethanol, and hexane for 18 h. Biodiesel synthesis reactions, using a single step addition of 13% an acyl acceptor ethanol, showed that LipA was highly effective at converting palm oil into biodiesel.


Surgeon-Led Initiatives to Increase Access to Surgical Treatment of Epilepsy at an Academic Level 4 Epilepsy Center: An Observational Cohort Study.
Underutilization of surgical treatment for epilepsy is multifactorial, and the multidisciplinary nature of caring for these patients represents a significant hurdle in expanding surgical treatment of epilepsy. To develop internal and external surgical referral relationships for patients with medically refractory epilepsy with the goal of improving access to care. To expand access to surgical epilepsy treatment at University of California (UC)-Irvine, 4 broad approaches focused on developing referral relationships and process improvement of surgical evaluation were undertaken in 2015 and 2016. The authors performed a retrospective review of all surgical epilepsy case referrals of the senior author from 2014 through 2020. Epilepsy surgical volume at UC-Irvine increased from an average of 5.2 cases annually to 32 cases in the first year (2015) of implementation. There was continued case volume growth from 2015 through 2020 to 52 procedures in the most recent year (P = .03). Hospital payments for epilepsy procedures increased from $1.09M in 2015 to $2.02M and $1.8M in 2019 and 2020 (P < .01), respectively, while maintaining a diverse payer mix. 79.4% of these patients did not have a previously established option for surgical epilepsy care. We outline strategies that level 4 epilepsy centers may use to strengthen collaborations and improve patient access for surgical epilepsy treatment. Increased collaboration can both improve the number of patients with epilepsy with access to specialized surgical care and produce reimbursement benefits for the centers caring for these patients, regardless of insurance source.


A comparison of the cell-binding characteristics of the mitogenic and nonmitogenic lectins from lima beans.
Using the two lectins from lima bean, we have tested the model for mitogenic stimulation of lymphocytes proposed by Prujansky et al. (Prujansky, A., Ravid, A., and Sharon, N. (1978) Biochim. Biophys. Acta 508, 137-146). The lectins used, a tetramer with two saccharide-binding sites and an octamer with four binding sites, are specific for N-acetyl-D-galactosamine. Our results show that cooperative binding may not be a prerequisite for mitogenicity of all lectins. We found that neither the weakly mitogenic tetramer nor the potently mitogenic octamer bound cooperatively to bovine lymphocytes. The strong mitogen bound with a higher affinity than the weak mitogen and fewer mitogen molecules bound to the lymphocyte surface at saturation. Competitive binding experiments indicated that both lectins bound to the same receptors. Our results suggest that the mitogenic lectin is able to bind and cross-link more membrane receptors. We have also studied the binding of the lima bean lectins to human red blood cells of types A, AB, B, and O. Both lectins bound cooperatively to type A and type AB cells and our data indicate that the lima bean lectins bind predominantly to the type A determinant.


The monocortical critical size bone defect as an alternative experimental model in testing bone substitute materials.
Reproducibility and comparability are prerequisites in testing bone substitute materials in an animal study. Various animal test models are used. The standard in testing bone substitute materials is the so-called critical size defect (CSD) model described by Schmitz and Hollinger. In most studies a bicortical (full thickness defect) CSD is used. In this study, monocortical defects (10 x 10 mm) in calvarias of adult pigs were created and compared to examine the spontaneous physiologic healing process and the required criteria for a CSD. Regeneration of defects, either filled using autogenous bone (group 1) or unfilled (group 2), was evaluated by means of microradiography and light microscopy after 2, 4, 12, 26, and 52 weeks. No complete osseous regeneration was found microradiographically and light microscopically in the control group at week 52 (nonmineralized area: 30% +/- 1.7%; mineralized area: 55% +/- 1.7%; bone marrow area: 15% +/- 1.7%). Defects treated with autogenous bone showed a 100% osseous defect filling after 26 weeks. The monocortical CSD fulfills the requirements for a CSD and represents a procedure which can be handled simply for investigations focusing on bone regeneration and testing of bone substitute materials.


Influence of visual inputs on quasi-static standing postural steadiness in individuals with spinal cord injury.
Postural steadiness while standing is impaired in individuals with spinal cord injury (SCI) and could be potentially associated with increased reliance on visual inputs. The purpose of this study was to compare individuals with SCI and able-bodied participants on their use of visual inputs to maintain standing postural steadiness. Another aim was to quantify the association between visual contribution to achieve postural steadiness and a clinical balance scale. Individuals with SCI (n = 15) and able-bodied controls (n = 14) performed quasi-static stance, with eyes open or closed, on force plates for two 45 s trials. Measurements of the centre of pressure (COP) included the mean value of the root mean square (RMS), mean COP velocity (MV) and COP sway area (SA). Individuals with SCI were also evaluated with the Mini-Balance Evaluation Systems Test (Mini BESTest), a clinical outcome measure of postural steadiness. Individuals with SCI were significantly less stable than able-bodied controls in both conditions. The Romberg ratios (eyes open/eyes closed) for COP MV and SA were significantly higher for individuals with SCI, indicating a higher contribution of visual inputs for postural steadiness in that population. Romberg ratios for RMS and SA were significantly associated with the Mini-BESTest. This study highlights the contribution of visual inputs in individuals with SCI when maintaining quasi-static standing posture.


Cryptococcal meningitis: initial presentation of acquired immunodeficiency syndrome.
Cryptococcal meningitis is an infrequent primary presentation of acquired immunodeficiency syndrome (AIDS). We report the case of a 33-year-old man with previously undiagnosed AIDS who presented with gait disturbance, acute blindness, and rapidly fatal neurologic deterioration. Cryptococcal meningitis was diagnosed by India ink smear and AIDS was diagnosed by Western Blot testing.


Acacetin-loaded microemulsion for transdermal delivery: preparation, optimization and evaluation.
Acacetin is reported as a potential drug candidate for the treatment of atrial fibrillation. However, clinical applications are limited by poor water solubility, limited ethanol solubility, and extremely low oral bioavailability. The present study prepared and evaluated acacetin-loaded microemulsion (ME) to achieve efficient pharmacokinetics together with no or minimal invasiveness for transdermal delivery. The formulation of ME was determined by the water titration method based on solubility results. The optimized formulation was achieved by the simplex lattice experiment design. The optimized ME formulations FA, FB and FC (FA with 10% and 50% DMSO as enhancers, respectively) were evaluated by ex vivo permeation with Franz diffusion cell and excised mice skin. In vivo pharmacokinetic studies were also performed at 8 mg/kg in rats within 6 h by transdermal administration. The optimal ME (FA) was comprised of 12.2% caprylic acid decanoate monoditriglyceride (MCF-NF), 39.8% Smix (RH40: Trans = 2:1 w/w) and 48% water, respectively. Acacetin-loaded FA with particle size 36.0 ± 3.6 nm and drug solubility 803.7 ± 32.1 mg/g was prepared. FB had significantly higher cumulative amounts and higher AUC0-∞ (196.6 ± 11.0 min × μg/mL, p < 0.05) than that FA alone (121.4 ± 33.1 min × μg/mL). The formulation of ME combined with the penetration enhancer can effectively improve the solubility and percutaneous absorption efficiency of acacetin, providing a new option for the non-invasive delivery of acacetin.


Cup is essential for oskar mRNA translational repression during early Drosophila oogenesis.
Study of the timing and location for mRNA translation across model systems has begun to shed light on molecular events fundamental to such processes as intercellular communication, morphogenesis, and body pattern formation. In D. melanogaster, the posterior mRNA determinant, oskar, is transcribed maternally but translated only when properly localized at the oocyte's posterior cortex. Two effector proteins, Bruno1 and Cup, mediate steps of oskar mRNA regulation. The current model in the field identifies Bruno1 as necessary for Cup's recruitment to oskar mRNA and indispensable for oskar's translational repression. We now report that this Bruno1-Cup interaction leads to precise oskar mRNA regulation during early oogenesis and, importantly, the two proteins mutually influence each other's mRNA expression and protein distribution in the egg chamber. We show that these factors stably associate with oskar mRNA in vivo. Cup associates with oskar mRNA without Bruno1, while surprisingly Bruno1's stable association with oskar mRNA depends on Cup. We demonstrate that the essential factor for oskar mRNA repression in early oogenesis is Cup, not Bruno1. Furthermore, we find that Cup is a key P-body component that maintains functional P-body morphology during oogenesis and is necessary for oskar mRNA's association with P-bodies. Therefore, Cup drives the translational repression and stability of oskar mRNA. These experimental results point to a regulatory feedback loop between Bruno 1 and Cup in early oogenesis that appears crucial for oskar mRNA to reach the posterior pole and its expression in the egg chamber for accurate embryo development.


Electronic Ordering System Improves Postoperative Pain Management After Total Knee or Hip Arthroplasty.
The authors investigated the impact of computerized provider order entry (CPOE) on the delivery times of analgesia and subsequent patient outcomes. We hypothesized that patients would report less pain and use less pain medications compared with the previous paper-based system. Two groups of patients after a total hip (THA) or knee arthroplasty (TKA) were retrospectively compared: one comprising 106 patients when the paper-based ordering system was in effect (conventional group), and one comprising 96 patients after CPOE was installed (electronic group). All patients received a regional anaesthetic at surgery (combined spinal-epidural). TKA patients also received a single-injection femoral nerve block. After transfer to the postoperative anaesthesia care unit (PACU), a patient-controlled epidural analgesia (PCEA) infusion was initiated. The following data was collected from the PACU record: time to initiation of analgesia, visual analog scale (VAS) pain scores at initiation of analgesia and hourly for the first postoperative day (POD), volume of pain medication used, length of stay (LOS) in the PACU and the hospital. The time to initiation of analgesia from arrival in the PACU was significantly lower in the electronic group compared to the conventional group (24.5 ± 28.3 minutes vs. 51.1 ± 26.2 minutes; mean ± SD, p < 0.001), as were VAS pain scores (0.82 ± 1.08 vs. 1.5 ± 1.52, p < 0.001) and the volume of PCEA needed to control pain (27.9 ± 20.2 ml vs. 34.8 ± 20.3 ml, p = 0.001) at 4 hours postoperatively. PACU LOS and hospital LOS did not significantly differ in the two groups. After implementation of CPOE, patients received their postoperative analgesia faster, had less pain, and required less medication.


The basics of commonly used molecular techniques for diagnosis, and application of molecular testing in cytology.
Molecular diagnostics has expanded to become the standard of care for a variety of solid tumor types. With limited diagnostic material, it is often desirable to use cytological preparations to provide rapid and accurate molecular results. This review covers important pre-analytic considerations and limitations, and a description of common techniques that the modern cytopathologist should understand when ordering and interpreting molecular tests in practice.


Persistent production of neurons from adult brain stem cells during recovery after stroke.
Neural stem cells in the subventricular zone of adult rodents produce new striatal neurons that may replace those that have died after stroke; however, the neurogenic response has been considered acute and transient, yielding only small numbers of neurons. In contrast, we show herein that striatal neuroblasts are generated without decline at least for 4 months after stroke in adult rats. Neuroblasts formed early or late after stroke either differentiate into mature neurons, which survive for several months, or die through caspase-mediated apoptosis. The directed migration of the new neurons toward the ischemic damage is regulated by stromal cell-derived factor-1alpha and its receptor CXCR4. These results show that endogenous neural stem cells continuously supply the injured adult brain with new neurons, which suggests novel self-repair strategies to improve recovery after stroke.


ABCB10 depletion reduces unfolded protein response in mitochondria.
Mitochondria have many functions, including ATP generation. The electron transport chain (ETC) and the coupled ATP synthase generate ATP by consuming oxygen. Reactive oxygen species (ROS) are also produced by ETC, and ROS damage deoxyribonucleic acids, membrane lipids and proteins. Recent analysis indicate that mitochondrial unfolded protein response (UPRmt), which enhances expression of mitochondrial chaperones and proteases to remove damaged proteins, is activated when damaged proteins accumulate in the mitochondria. In Caenorhabditis elegans, HAF-1, a putative ortholog of human ABCB10, plays an essential role in signal transduction from mitochondria to nuclei to enhance UPRmt. Therefore, it is possible that ABCB10 has a role similar to that of HAF-1. However, it has not been reported whether ABCB10 is a factor in the signal transduction pathway to enhance UPRmt. In this study, ABCB10 was depleted in HepG2 cells using small interfering RNA (siRNA), and the effect was examined. ABCB10 depletion upregulated ROS and the expression of ROS-detoxifying enzymes (SOD2, GSTA1, and GSTA2), and SESN3, a protein induced by ROS to protect the cell from oxidative stress. In addition, ABCB10 depletion significantly decreased expression of UPRmt-related mitochondrial chaperones (HSPD1 and DNAJA3), and a mitochondrial protease (LONP1). However, the putative activity of ABCB10 to export peptides from mitochondria was not lost by ABCB10 depletion. Altogether, these data suggest that ABCB10 is involved in UPRmt signaling pathway similar to that of HAF-1, although ABCB10 probably does not participate in peptide export from mitochondria.


Increased endovascular interventions decrease the rate of lower limb artery bypass operations without an increase in major amputation rate.
Progression of peripheral vascular disease may lead to major amputations. We sought to understand whether more frequent endovascular angioplasty and stenting in patients with limb-threatening ischemia would affect the number of major amputations. We retrospectively reviewed the effects of implementing more frequent endovascular intervention for the 4 years 2003-2006 at the Veterans Affairs Medical Center in Long Beach, California. During this interval angioplasty became the preferred method for the treatment of infrainguinal vascular disease. Open bypass procedures were performed for patients with limb-threatening ischemia and extensive lesions that could not be treated by angioplasty. Patients were on average 68 +/- 1 years, and 96% were male. The patients were 45% active smokers, with 43% diabetics. There was 0% 30-day mortality for both groups over the 4 years. the number of below-the-knee, above-the-knee, and transmetatarsal amputations for fiscal years 2003, 2004, 2005, and 2006 were, 42, 50, 62, and 41, respectively. Concurrently, there has been a reduction in open femoral to popliteal or trifurcation vessel bypasses with 37, 43, 28, and 14 procedures for 2003, 2004, 2005, and 2006. Angioplasty and stenting increased from 12, 12, 24, to 59 over the same period. Patients who had a femoral to distal bypass were more likely to have an amputation than those undergoing angioplasty (odds ratio = 4.2, 95% confidence interval 1.6-11.5) for those with at least 1 year of follow-up, likely due to these patients having more severe disease. Increasing the frequency of angioplasty for infrainguinal vascular lesions did not increase the number of major lower extremity amputations in our stable patient population.


A miniaturized organic photoelectrochemical transistor aptasensor based on nanorod arrays toward high-sensitive T-2 toxin detection in milk samples.
Detection of T-2 toxin is of great significance to environment and human health, as T-2 toxin is one of the main toxins that contaminate crops, stored grain and other food. Herein, a zero-gate-bias organic photoelectrochemical transistor (OPECT) sensor was proposed based on nanoelectrode arrays as gate photoactive materials which can result in the accumulation of photovoltage and preferable capacitance leading to better sensitivity of the OPECT. For comparison, the channel current of OPECT was 100 times higher than photocurrent of conventional photoelectrochemical (PEC) attributing to remarkable signal amplification of OPECT. It was also found that the detection limit of OPECT aptasensor was as low as 28.8 pg/L, lower than 0.34 ng/L of the conventional PEC method, further indicating the advantage of the OPECT devices in T-2 toxin determination. This research has been successfully applied in real sample detection which provided a general platform of OPECT for food safety analysis.


Auger electrons and DNA double-strand breaks studied by using iodine-containing chemicals.
Irradiation of high Z elements such as iodine, gold, gadolinium with monochromatic X-rays causes photoelectric effects that include the release of Auger electrons. Decay of radioactive iodine such as I-123 and I-125 also results in multiple events and some involve the generation of Auger electrons. These electrons have low energy and travel only a short distance but have a strong effect on DNA damage including the generation of double-strand breaks. In this chapter, we focus on iodine and discuss various studies that used iodine-containing chemicals to generate Auger electrons and cause DNA double-strand breaks. First, DNA synthesis precursors containing iodine were used to place iodine on DNA. DNA binding dyes such as iodine Hoechst were investigated for Auger electron generation and DNA breaks. More recently, iodine containing nanoparticles were developed. We describe our study using tumor spheroids loaded with iodine nanoparticles and synchrotron-generated monochromatic X-rays. This study led to the demonstration that an optimum effect on DNA double-strand break formation is observed with a 33.2keV X-ray which is just above the K-edge energy of iodine.


Cannabidiol in refractory status epilepticus: A review of clinical experiences.
To summarize and evaluate clinical experiences with refractory status epilepticus in which cannabidiol (CBD) was utilized for cessation of seizure activity. A comprehensive literature review was performed on PubMED, MEDLINE, Scopus, and CINAHL between May - June 2022 with the assistance of a medical reference librarian using the following search terms: "Cannabidiol" [MAJR], "Status Epilepticus" [MAJR], "New-Onset Refractory Status Epilepticus", and "cannabidiol." Reports that provided dosing regimens and patient outcomes were included. Thirty-two articles were screened. Five articles were selected for inclusion in this review and detailed the clinical courses of 11 patients. Five of the 11 patients received CBD during the chronic epilepsy stage, while the remaining 6 received it during a period of acute status epilepticus. Patients were trialed on an average of 9 anti-epileptic drugs prior to CBD administration, after which 9 of the 11 patients experienced a reduction of seizure activity. Dosing of CBD ranged between 5-25 mg/kg/day and was titrated based on patient response to therapy. Adverse effects were relatively benign and were generally limited to gastrointestinal discomfort, reported after seizure cessation. CBD may provide a potentially efficacious and safe management strategy in refractory status epilepticus, including patients with new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome. A potential for drug-drug interactions between CBD and anti-epileptic drugs warrants judicious monitoring. Additional research is necessary to determine a definitive dosing strategy for this agent.


High-sensitivity C-reactive protein levels in players on a major league baseball team.
We performed a high-sensitivity C-reactive protein test in major league baseball players. This test was of limited usefulness on preseason physical examination of 50 major league baseball players. The test is more likely to be of greater value performed on those whose 10-year risk of coronary heart disease is in the 10% to 20% range.


Investigation of polyamine metabolism by high-performance liquid chromatographic and gas chromatographic profiling methods.
Measurements of polyamines, polyamine conjugates and their metabolites in tissues, cells and extracellular fluids are used in biochemistry, (micro)biology, oncology and parasitology. Decarboxylation of ornithine yields putrescine. Aminopropylation of putrescine yields spermidine, and aminopropylation of spermidine yields spermine. Spermidine and spermine are retroconverted to putrescine and spermidine, respectively, by initial N-acetylation and subsequent polyamine oxidation. The intermediate N-acetylputrescine, N1-acetylspermidine and N8-acetylspermidine are the major urinary N-acetylpolyamines. Polyamines and N-acetylpolyamines are terminally degraded to non-alpha-amino acid metabolites by oxidative deamination and aldehyde dehydrogenation. Chromatography with on-line detection is the most commonly applied profiling method for polyamines, N-acetylpolyamines and their non-alpha-amino acid metabolites. Cation-exchange and reversed-phase high-performance liquid chromatography require pre- or post-column derivatisation, followed by UV-Vis spectrophotometric or fluorimetric detection. Isolation and derivatisation precedes gas chromatography with flame-ionisation, nitrogen-phosphorus, electron-capture or mass spectrometric detection. High-performance liquid chromatography and gas chromatography of polyamines are not competitive techniques, but rather supplementary.


Intraventricular infusion of vascular endothelial growth factor promotes cerebral angiogenesis with minimal brain edema.
Therapeutic cerebral angiogenesis, i.e., using angiogenic factors to enhance collateral vessel formation within the central nervous system, is a potential method for cerebral revascularization. Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen that also increases capillary permeability, particularly in ischemic tissue. The purpose of this study was to assess the angiogenic and capillary permeability effects of chronic intraventricular infusion of exogenous VEGF in nonischemic brain tissue, because many patients with impaired cerebrovascular reserve do not exhibit chronic cerebral ischemia. Recombinant human VEGF(165) was infused into the right lateral ventricle of rats at a rate of 1 microl/h for 7 days, at concentrations of 1 to 25 microg/ml, with osmotic minipumps. Control animals received vehicle only. Vessels were identified in laminin immunohistochemical analyses. Capillary permeability and brain edema were assessed with Evans blue extravasation, [(3)H]inulin permeability, and brain water content measurements. Vessel density was dose-dependently increased by VEGF(165) infusions, with significant increases occurring in animals treated with 5 or 25 microg/ml, compared with control animals (P h 0.01). Significant enlargement of the lateral ventricles was observed for the highest-dose group but not for animals treated with other doses. Capillary permeability was assessed in animals treated with a dose of 5 microg/ml. An increase in capillary permeability in the diencephalon was identified with Evans blue extravasation and [(3)H]inulin permeability assessments; however, the brain water content was not significantly increased. Chronic intraventricular infusions of VEGF(165) increased vascular density in a dose-dependent manner. There seems to be a therapeutic window, because infusion of VEGF(165) at a concentration of 5 microg/ml resulted in a significant increase in vessel density with minimal associated brain edema and no ventriculomegaly.


Nomogram For Preoperative Prediction Of Microvascular Invasion Risk In Hepatocellular Carcinoma.
To preoperatively predict the microvascular invasion (MVI) risk in hepatocellular carcinoma (HCC) using nomogram. A retrospective cohort of 513 patients with HCC hospitalized at Xiangya Hospital between January 2014 and December 2018 was included in the study. Univariate and multivariate analysis was performed to identify the independent risk factors for MVI. Based on the independent risk factors, nomogram was established to preoperatively predict the MVI risk in HCC. The accuracy of nomogram was evaluated by using receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA). Tumor size (OR=1.17, 95% CI: 1.11-1.23, p<0.001), preoperative AFP level greater than 155 ng/mL (OR=1.65, 95% CI: 1.13-2.39, p=0.008) and NLR (OR=1.14, 95% CI: 1.00-1.29, p=0.042) were the independent risk factors for MVI. Incorporating these 3 factors, nomogram was established with the concordance index of 0.71 (95% CI, 0.66-0.75) and well-fitted calibration curves. DCA confirmed that using this nomogram added more benefit compared with the measures that treat all patients or treat none patients. At the cutoff value of predicted probability ≥0.44, the model demonstrated sensitivity of 61.64%, specificity of 71.53%, positive predictive value (PPV) of 64.13%, and negative predictive value (NPV) of 69.31%. Nomogram was established for preoperative prediction of the MVI risk in HCC patients, and better therapeutic choice will be made if it was applied in clinical practice.


Feature-guided deep learning reduces signal loss and increases lesion CNR in diffusion-weighted imaging of the liver.
This research aims to develop a feature-guided deep learning approach and compare it with an optimized conventional post-processing algorithm in order to enhance the image quality of diffusion-weighted liver images and, in particular, to reduce the pulsation-induced signal loss occurring predominantly in the left liver lobe. Data from 40 patients with liver lesions were used. For the conventional approach, the best-suited out of five examined algorithms was chosen. For the deep learning approach, a U-Net was trained. Instead of learning "gold-standard" target images, the network was trained to optimize four image features (lesion CNR, vessel darkness, data consistency, and pulsation artifact reduction), which could be assessed quantitatively using manually drawn ROIs. A quality score was calculated from these four features. As an additional quality assessment, three radiologists rated different features of the resulting images. The conventional approach could substantially increase the lesion CNR and reduce the pulsation-induced signal loss. However, the vessel darkness was reduced. The deep learning approach increased the lesion CNR and reduced the signal loss to a slightly lower extent, but it could additionally increase the vessel darkness. According to the image quality score, the quality of the deep-learning images was higher than that of the images obtained using the conventional approach. The radiologist ratings were mostly consistent with the quantitative scores, but the overall quality ratings differed among the readers. Unlike the conventional algorithm, the deep-learning algorithm increased the vessel darkness. Therefore, it may be a viable alternative to conventional algorithms.


Immunization of Wistar female rats with 255-Gy-irradiated Toxoplasma gondii: Tissue parasitic load and lactogenic quantification.
Toxoplasma gondii is one of the most significant parasite, due its importance in veterinary medicine and in public health, considered a food-borne pathogens, there is no available drug treatments to eliminate it from animal tissue, this reinforce the search for a vaccine against this parasite. This study was aimed to evaluate the dynamic of the distribution of T. gondii in tissues of female Wistar rats and their milk, after the immunization by oral rote with irradiated tachyzoites. One week after pregnancy confirmation, rats was challenged by gavage with T. gondii bradyzoites, oocysts or tachyzoites of T. gondii. Forty-eight pregnant rats were grouped as follows: immunized and challenged with bradyzoites (BZ*); non-immunized and challenged with bradyzoites (BZ); immunized and challenged with oocysts (OC*); non-immunized and challenged with oocysts (OC); immunized and challenged with tachyzoites (TZ*); non-immunized and challenged with tachyzoites (TZ); only immunized (I); control group (C). After parturition, milk samples were collected for 3 weeks and then rats were sacrificed and the tissues and milk samples were researched for T. gondii parasite load determined by the quantitative PCR (qPCR). It was verified that the immunization with irradiated tachyzoites of T. gondii induced the reduction of parasitic load in muscle samples in rats challenged by bradyzoites and oocysts, although not enabled the development of sterile immunity. The detection of parasite DNA in milk was found throughout the lactation period, from immunized and non-immunized rats, however no differences were found in the parasite load caused by immunization.


Use of bile cytology for early diagnosis of complications in orthotopic liver transplantation.
We conducted a daily analysis of bile cellularity in 25 patients undergoing 29 orthotopic liver transplants (OLT) and correlated the cytological parameters with the clinical outcome of each patient. The 16 patients without complications only showed slides with cells during the first 4-5 postoperative days. The four patients with primary non-function (PNF) of the graft had a high cell density up to the time of the retransplant, with a preponderance of polymorphonuclear (PMN) leucocytes (59.2%) and epithelial cells (29.2%). During the episodes of sepsis (n = 3) and rejection (n = 7) we noted the sudden appearance of high cellularity, almost exclusively PMN leucocytes (96.5%), and a preponderance of PMN leucocytes (84.2%) with appreciable percentages of mononuclear cells and macrophages as well as the early appearance of lymphoblasts in the rejection episodes. Our results show that bile cytology can be a useful method for diagnosing graft complications in liver transplantation.


Clinical Advantages of Angled Screw Access Channels for Implant-Supported Restorations in the Esthetic Zone.
Retained cement following delivery of an implant-supported crown is strongly associated with peri-implant mucositis and peri-implantitis, and screw retention is a strategy for avoiding this problem entirely. In the esthetic zone, screw retention compromises esthetics unless the screw access in the crown is concealed to the palatal of the incisal edge. To avoid positioning the implant platform excessively toward the palate, practitioners can design an angled screw access channel in the crown. A healthy 22-year-old patient with nonrestorable tooth #9 received extraction and immediate implant placement with immediate provisionalization. The screw access channel for the provisional restoration involved the incisal edge. Rather than placing a custom abutment and cementing the definitive restoration, an angled screw access channel was employed. The implant-supported restoration exhibited favorable esthetics, and the possibility of retained cement was avoided. Up to a point, positioning maxillary anterior implants toward the palate is favorable. When the long axis of the implant is directed between the incisal edge and the cingulum of adjacent teeth, the implantsupported crown can be screw retained without compromising esthetics. In immediate implant situations, such positioning also increases the distance between the implant and the facial alveolar bone and encourages a favorable position of the marginal peri-implant mucosa. However, an excessively palatal platform position compels a restoration with irregular contours, which can frustrate proper oral hygiene and professional maintenance. Angled screw access channels allow screw retention without excessive palatal positioning of the platform, avoiding the possibility of cement-related peri-implant disease.


The combination of PCR and serology increases the diagnosis of Pseudomonas aeruginosa colonization/infection in cystic fibrosis.
Early diagnosis of Pseudomonas aeruginosa colonization/infection in patients with cystic fibrosis (CF) using microbiological culturing methods may be difficult. Serology and polymerase chain reaction (PCR) may be useful techniques for early detection of P. aeruginosa in children with CF. A cross-sectional analysis comparing results obtained by three different methods for P. aeruginosa identification was performed in 87 CF patients with a mean age of 9.7 years. Microbiological culturing and PCR targeting the algD GDP mannose dehydrogenase gene of P. aeruginosa were performed in sputum or oropharyngeal swabs samples, and serum antibodies against three P. aeruginosa antigens (elastase, alkaline protease, and exotoxin A) were assessed once. It was possible to isolate P. aeruginosa by culture in samples from 42 patients (48.2%), while PCR was positive in 53 (60.9%) patients. Serology was positive in 38 patients (43.6%), with a higher positivity for elastase (37.9%), followed by alkaline protease (29.9%) and exotoxin A (19.5%). The difference among the three isolated methods was not statistically significant. The combination of PCR + serology was significantly superior to single methods, to PCR + culture and also to culture + serology. PCR identified a higher number of patients with P. aeruginosa than serology and conventional culture, but the difference did not reach statistical significance. Any of the combination methods that included PCR resulted in significantly statistical differences in relation to isolated microbiological or serology methods, but not to the PCR method alone, suggesting that PCR may be the main additive method for P. aeruginosa identification.


Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal neurones by adenosine A1 receptor activation.
The effect of the stable adenosine analogue, 2-chloro-adenosine (CADO), on the currents elicited by iontophoretic application of N-methyl-D-aspartate (NMDA) to pyramidal cells acutely dissociated from the CA1 area of the rat hippocampus was studied using the patch-clamp technique in the whole-cell configuration. CADO (3-300 nM) reversibly inhibited NMDA receptor-mediated currents (maximal effect: 54.2 +/- 6.6% decrease, EC50 = 10.3 nM). This effect was prevented by the adenosine A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) (50 nM). CADO (100 nM inhibited the conductance induced by iontophoretic application of NMDA, without changing its reversal potential, in both the absence and the presence of Mg2+ (30 microM). Adenosine may contribute to the regulation of the NMDA receptor function, particularly under conditions, like hypoxia and ischaemia, leading to excessive NMDA receptor activation.


A versatile photochromic dithienylethene-containing β-diketonate ligand: near-infrared photochromic behavior and photoswitchable luminescence properties upon incorporation of a boron(III) center.
A versatile dithienylethene-containing β-diketonate ligand and its boron(III) compounds have been successfully synthesized. Upon photocyclization, the ligand shows a new absorption band at 630 nm with good fatigue resistance and high thermal stability. Incorporation of the boron center has been demonstrated to shift the photochromic behavior to the NIR region.


One Health Implications of Antimicrobial Resistance in Bacteria from Amazon River Dolphins.
Studies on the microbiota of freshwater cetaceans are scarce and may provide important data on animal and environmental health. This study aimed to evaluate the antimicrobial susceptibility of Gram-negative bacteria recovered from two populations of free-ranging Amazon river dolphins (Inia geoffrensis). Twenty-one animals were captured and released, 13 from Negro River and 8 from Tapajós River, Brazil. Swab samples were obtained from the oral cavity, blowhole, genital opening and rectum and were cultured on MacConkey agar. Isolates were biochemically identified, and antimicrobial susceptibility was assessed by disk diffusion method. Overall, 132 isolates were recovered, of which 71 were recovered from animals from Negro River and 61 from Tapajós River. The most commonly recovered bacterial species were Enterobacter cloacae, Morganella morganii, Klebsiella pneumoniae and Pseudomonas aeruginosa. Overall, 51.6% (63/122) of the isolates were not-susceptible (intermediate resistance and resistance), of which 28/122 (22.9%) were resistant to at least one antimicrobial. Cephalothin, cefuroxime and cefepime were the drugs to which more resistant and intermediate results were observed (P < 0.001). The results indicate that free-ranging Amazon river dolphins host resistant bacteria, contributing for their maintenance in the environment. This study highlights the importance of the One Health approach to monitor the emergence of antimicrobial resistance. Summary Gram-negative bacteria recovered from 21 free-ranging Amazon river dolphins (Inia geoffrensis) from the Negro River and the Tapajós River populations were evaluated for their antimicrobial susceptibility. Overall, 51.6% (63/122) of the isolates were not-susceptible (intermediate resistance and resistance), of which 28/122 (22.9%) were resistant to at least one antimicrobial. Cephalothin, cefuroxime and cefepime were the drugs to which more resistant and intermediate results were observed. Thus, free-ranging Amazon river dolphins, never treated with antimicrobials, host resistant bacteria, contributing for their maintenance in the environment and highlighting the importance of the One Health approach to monitor the emergence of antimicrobial resistance.


Comparative Assessment of Leukocyte Infiltrate Composition in the Uterine and Vaginal Tissues in Rats with Experimental Endomyometritis Treated with Interferon-γ at Different Times of the Day.
The cell composition of leukocyte infiltrates in the endometrium, myometrium, and vaginal walls was studied in Wistar rats with modeled chronic endomyometritis after administration of IFNγ (0.1 μg/100 g body weight) in different daily regimens (10.00 or 20.00). Morning injections of this cytokine ameliorated inflammatory infiltration of the uterine wall and vagina, but increased the content of neutrophils in the endometrium. Evening cytokine injections reduced neutrophilic infiltration, enhanced mononuclear infiltration, and had no effect on plasmacytic infiltration of the uterine and vaginal walls. In the vaginal wall, both IFNγ administration schedules decreased neutrophil content. The data indicate the necessity to take into account the circadian rhythms in IFN therapy.


Erasure of fear memories is prevented by Nogo Receptor 1 in adulthood.
Critical periods are temporary windows of heightened neural plasticity early in development. For example, fear memories in juvenile rodents are subject to erasure following extinction training, while after closure of this critical period, extinction training only temporarily and weakly suppresses fear memories. Persistence of fear memories is important for survival, but the inability to effectively adapt to the trauma is a characteristic of post-traumatic stress disorder (PTSD). We examined whether Nogo Receptor 1 (NgR1) regulates the plasticity associated with fear extinction. The loss of NgR1 function in adulthood eliminates spontaneous fear recovery and fear renewal, with a restoration of fear reacquisition rate equal to that of naive mice; thus, mimicking the phenotype observed in juvenile rodents. Regional gene disruption demonstrates that NgR1 expression is required in both the basolateral amygdala (BLA) and infralimbic (IL) cortex to prevent fear erasure. NgR1 expression by parvalbumin expressing interneurons is essential for limiting extinction-dependent plasticity. NgR1 gene deletion enhances anatomical changes of inhibitory synapse markers after extinction training. Thus, NgR1 robustly inhibits elimination of fear expression in the adult brain and could serve as a therapeutic target for anxiety disorders, such as PTSD.


Private property and public health reform in England 1830-70.
British cities of the mid-nineteenth century were unsanitary. In many cases lack of street paving, insufficient water, proliferating cesspools and open sewers turned them into cloying, degrading and offensive mires. Many of the urban workers, too poor to pay rent sufficient to meet the costs of these environmental services, were shuffled among damp dingy rooms into which the sun shone feebly and in which their physical odours were confined against any draughts. The relations between landlord and tenant were circumscribed by the indebtedness of the former and the penury of the latter. Water, sewerage and housing standards were left to the sway of the market while the effective demand for them was limited by low real wages. In the largest cities this filth was dangerous as well as offensive and public health reforms became ever more pressing. Yet the form in which this legislation was secured and the manner in which it was implemented were not as straightforward as this sketch of their crying necessity might suggest.


Facile nucleophilic substitution at the C3a tertiary carbon of the 3a-bromohexahydropyrrolo[2,3-b]indole scaffold.
The synthesis of 3a-substituted hexahydropyrrolo[2,3-b]indole derivatives via nucleophilic substitution at the C3a position is reported. Nitrogen-, oxygen-, sulfur-, fluoro- and carbon-based nucleophiles have been employed, using both conventional organic solvents and ionic liquids. The C3a-substituted derivatives were obtained in good to excellent yields.


Knowledge, attitude, and practice instruments for urinary incontinence: A psychometric review.
To analyze the psychometric properties of instruments measure knowledge and/or attitude and/or practice related to urinary incontinence (UI). This review was conducted in September 2018 without restrictions regarding language and year of publication. MEDLINE/PubMed, CINAHL, SCOPUS, PsycINFO, Web of Science, Cochrane, LILACS, and Google. The psychometric properties were evaluated using the COnsensus-based Standards for the selection of health status Measurement INstruments and the Quality Criteria for Measurement Properties. A total of seven articles published between 1999 and 2018 were included. The evaluation of the psychometric properties showed that the majority of the instruments presented "excellent" or "good" methodological quality; however, the description of aspects related to the validation stages was inadequate in some studies, causing the quality of the results to be evaluated as "indeterminate" in some properties. This review cannot recommend any questionnaire without reservations; however, the Urinary Incontinence Scales and the Barriers Incontinence Care Seeking Questionnaire presented better evaluations, regarding both methodological quality and the quality of the results. This review provides a strategy to select the most suitable instrument to assess knowledge, attitude, and practice regarding UI, according to the psychometric properties, guiding their use by researchers in clinical practice.


Between-grader repeatability of tear meniscus measurements using Fourier-domain OCT in patients with dry eye.
To examine the between-grader repeatability of height, depth, and cross-sectional area measurements of the lower tear meniscus, using a Fourier-domain optical coherence tomography (OCT) system. A total of 16 patients with dry eye had the lower tear meniscus of the right eye imaged twice in rapid succession. The tear meniscus height, depth, and cross-sectional area were measured by two masked graders using computer calipers. The between-grader variability, calculated using the pooled coefficient of variation (CV%), assessed the repeatability of the measurements. The between-grader CV% was 12.1%, 15.7%, and 19.5% for height, depth, and area, respectively. The between-image variability was 17.1%, 13.4%, and 35.4% for height, depth, and area, respectively. The overall intraclass correlation was 99%. There was no systematic bias between the two graders. Fourier-domain OCT demonstrates good between-grader and between-image repeatability in measuring the height, depth, and cross-sectional area of the tear meniscus in patients with dry eye. Measurement variability was primarily due to the difference between images rather than graders.