Comparison of anticonvulsant effect of pentobarbital and phenobarbital against seizures induced by maximal electroshock and picrotoxin in rats.
Pentobarbital and phenobarbital exhibited anticonvulsant effect against maximal electroshock (MES) and picrotoxin-induced seizures in rats. Bicuculline, a GABAA receptor antagonist, reversed the anticonvulsant effect of pentobarbital, but not of phenobarbital, at a dose having no effect per se. Although picrotoxin (2 mg/kg, IP) potentiated MES seizures, it did not reverse the anticonvulsant effect due to either pentobarbital or phenobarbital. GABAB receptor antagonists such as delta-amino-n-valeric acid and homotaurine failed to modify the anticonvulsant effect due to pentobarbital or phenobarbital. Furthermore, GABAA agonist muscimol but not baclofen, a GABAB receptor agonist, exhibited the anticonvulsant effect against MES-induced seizures. However, baclofen when combined with sub-effective dose of pentobarbital or phenobarbital offered protection against MES seizures. Pentobarbital and phenobarbital were effective in almost equivalent doses against MES, as well as against picrotoxin-induced seizures. These observations indicated that pentobarbital exhibits anticonvulsant effect against MES seizures through the involvement of GABAA receptors, and activation of GABAB receptors alone does not seem to play any significant role in MES seizures and in the anticonvulsant effect of pentobarbital. However, activation of GABAB receptor does potentiate the facilitatory effect of barbiturates on GABAAergic transmission and in their anti-MES effect. Moreover, these results also suggest that the anticonvulsant effect of barbiturates against MES-seizures may involve other mechanisms in addition to GABAAergic transmission.


The Use of Differential Scanning Fluorimetry to Assess Strigolactone Receptor Function.
Differential scanning fluorimetry (DSF) is a method used for assessing the interaction of ligands with proteins. In most cases binding of a ligand to proteins tends to increase the melting temperature (Tm) of the protein involved. However, in the case of strigolactone receptors (e.g., D14, AtD14, DAD2, RMS3) from plants, the Tm tends to be reduced in the presence of strigolactones. This is likely due to increased flexibility of the receptors in the presence of hormone ligands.DSF experiments are simple, fast, amenable to high-throughput formats, and cost effective. They have therefore gained in popularity, including within the field of SL signaling. Typically in DSF the receptor protein is purified and incubated with the ligand (strigolactone, agonist, or antagonist) and a (fluorescent) reporter dye. The mixture is then placed in a quantitative PCR instrument and subjected to an increasing temperature gradient. Changes in fluorescence are recorded along the gradient, as the dye interacts with unfolded portions of the protein becoming accessible when the protein "melts". Differences in the temperature at which the protein unfolds in the absence and in the presence of the ligand are interpreted as indicating interactions between the ligand and the receptor.


Sarcolemmal depolarization in sporadic inclusion body myositis assessed with muscle velocity recovery cycles.
To study patients with sporadic inclusion body myositis (sIBM) with muscle velocity recovery cycles (MVRC) to assess muscle membrane excitability, pathophysiological mechanisms and potential biomarkers of this disorder. MVRC were recorded from 20 individuals with sIBM from tibialis anterior (TA) and rectus femoris (RF) muscles. Excitability parameters were compared with MVRC data obtained from 22 normal controls >50 years. Muscle relative refractory period was prolonged in both TA (6.4 ms vs 4.4 ms, P < 0.001) and RF (7.1 ms vs 3.9 ms, P < 0.001) of sIBM affected muscle when compared to controls. Early supernormality was reduced in both TA (3.6% vs 8.8% P = 0.001) and in RF (mean 5.4% vs 13% P < 0.001). Late supernormality was only decreased significantly in sIBM affected TA (1.8% vs 3.6% P = 0.001) but not in RF. No consistent correlations between MVRC parameters and clinical markers of sIBM disease severity were found. The resting sarcolemmal muscle membrane potential of sIBM muscle is depolarized relative to that of normal controls, which may be related to intramuscular amyloid deposition in sIBM. Sarcolemmal depolarization may play a role in muscle dysfunction and weakness observed in sIBM patients.


Hemodynamic study of intravenous propionyl-L-carnitine in patients with ischemic heart disease and normal left ventricular function.
Propionyl-L-carnitine was given intravenously to ten patients with chronic ischemic heart disease who had normal left ventricular function and had not had a previous myocardial infarction. Subsequently, pulmonary and systemic circulation, left ventricular function, and the relationship between the ventricle and afterload were evaluated. This drug, at a dose of 15 mg/kg, improves ventricular function by easing the load and by enhancing cardiac efficiency. The ejection impedance is reduced with a consequent increase in stroke volume as a result of a) a decrease in systemic and pulmonary resistance and b) an increase in arterial compliance. Arterial pressure is maintained due to an increase in total external heart power. Since the tension time index shows a proportionally smaller increase in the energy requirement, it follows that cardiac efficiency has been improved and ventricle-afterload matching is optimal. These results suggest but do not prove that propionyl-L-carnitine exhibits a positive inotropic property.


Use of SAND balloon catheter for laparoscopic management of extremely large ovarian cysts.
The objective of the study was to assess the feasibility and outcome of laparoscopic surgery for management of extremely large ovarian cysts using the SAND balloon catheter. From January 2006 to December 2009, 25 patients with large cystic adnexal tumors underwent laparoscopic-assisted surgery using the SAND balloon catheter. Median (range) patient age was 43 (20-68) years, body mass index was 25 (19-32), mass size was 26 cm (15-60 cm), duration of the surgical procedure was 60 (30-300) minutes), and blood loss was 30 (10-100) mL. There were no major surgical complications. Intra-abdominal leakage of cyst fluid was observed in only 1 case (4%). With proper patient selection, the SAND balloon catheter can be extremely useful in laparoscopic removal of very large adnexal masses, without intraperitoneal spillage.


Correlation of echocardiographic probability of pulmonary hypertension with maternal outcomes in pregnant women with elevated right ventricular systolic pressure.
The use of echocardiography to evaluate the probability for pulmonary hypertension (PH) in pregnant women has not been reported or correlated with outcomes. We hypothesized that in women with elevated right ventricular systolic pressure (RVSP) on echocardiography first identified during pregnancy, those with low probability for PH would have fewer major adverse cardiac events (MACE). We performed a retrospective cohort study of pregnant women with RVSP >35 mm Hg on echocardiogram first identified during pregnancy. Women were classified as intermediate-high probability for PH (HP) or low probability for PH (LP) based on simplified European Society of Cardiology echocardiographic criteria. Maternal cardiac, obstetric, and fetal outcomes were assessed. A total of 77 women met inclusion criteria (mean age 30 ± 5 years), with 45 (58%) classified as HP and 32 (42%) as LP. There were 21 (27%) women who experienced MACE, more commonly in the HP cohort (HP 18 (40%) women vs. LP 3 (9%) women, P = .01). The echocardiographic criteria for intermediate-high probability of PH identified women at risk for MACE with 85% sensitivity and 52% specificity. The negative predictive value for MACE in women meeting low echocardiographic probability for PH criteria was 91%. In women with elevated RVSP on echocardiography first identified during pregnancy, those with low echocardiographic PH probability are at significantly lower risk for MACE during pregnancy, though the risk is not eliminated. This may be useful to risk stratify pregnant women with suspected PH, guiding tertiary care referral and invasive catheterization.


Pneumatosis Intestinalis in Children With Intestinal Failure: The Result of Intestinal Stress From Enteral Feeding?
The incidence and significance of pneumatosis intestinalis (PI) in children with a diagnosis of intestinal failure is not well understood. The aim of this study was to identify clinical and anatomical factors associated with the imaging findings of PI in patients with intestinal failure. We performed a retrospective review of all children with a diagnosis of intestinal failure at Children's Hospital Colorado between January 2019 and April 2022. Patients were stratified and compared based on the incidence of PI on abdominal imaging. Differences were compared using 2-sample Wilcoxon tests, chi-square, or Fisher exact tests. There were 111 patients identified with a diagnosis of intestinal failure and 30.6% (34) developed at least 1 instance of PI. There were no differences in etiology of intestinal failure or anatomy between those who developed PI and those who did not. Patients who developed PI, were less likely to be on total parental nutrition (60.6% vs 98.6%, P < 0.001) and more likely to be receiving any form of enteral feeds (87.9% vs 66.2%, P = 0.035) or tube feeds (75.8% vs 44.2%, P = 0.0045). Of the children with PI, 30.3% (10) were undergoing an enteral feed advancement at time of PI development. Three patients with PI underwent laparotomy for PI treatment, 2 of which were negative laparotomies. The development of PI in children with intestinal failure is likely a benign finding. It is associated with enteral feeding and may be due to increased intestinal stress.


Development and reliability of a correction factor for parent-reported adherence to pediatric antiepileptic drug therapy.
Study aims were (1) to document and examine associations between parent-report and electronic monitoring (EM) of pediatric antiepileptic drug (AED) adherence, (2) to determine the sensitivity and specificity of parent-reported adherence, and (3) to develop a correction factor for parent-reported adherence. Participants included 111 consecutive children with new-onset epilepsy (M(age) = 7.2 ± 2.0; 61.3% male; 75.8% Caucasian) and their primary caregivers. AED adherence was electronically monitored for 3 months prior to the 4-month clinic follow-up visit. Parent-reported adherence captured adherence 1-week prior to the clinic visit. For specificity/sensitivity analyses of parent-reported adherence, cut points of 50%, 80%, and 90% were used with electronically monitored adherence calculated 1-week prior to the clinic visit as the reference criterion. Electronically monitored adherence (80.3%) was significantly lower than parent-reported adherence (96.5%; p < 0.0001) 1-week prior to the clinic visit, but both were significantly correlated (rho = 0.46, p < 0.001). The 90% parent-reported adherence cut point demonstrated the most sensitivity and specificity to electronically monitored adherence; however, specificity was still only 28%. A correction factor of 0.83 was identified as a reliable adjustment for parent-reported adherence when compared to electronically monitored adherence. Although EM is the gold standard of adherence measurement for pediatric epilepsy, it is often not clinically feasible to integrate it into routine clinical care. Therefore, use of a correction factor for interpreting parent-reported adherence holds promise as a reliable clinical tool. With reliable adherence measurement, clinicians can provide adherence interventions with the hope of optimizing health outcomes for children with epilepsy.


Anthropogenic impacts on isotopic and geochemical characteristics of urban streams: a case study in Wuhan, China.
Urbanization and human activities have significantly modified the geochemical signatures of urban streams worldwide. However, the geochemical characteristics of urban streams in Wuhan, one of the core cities in the Yangtze River Economic Belt in China, remain largely unstudied. Here, we examined the stable isotopes and geochemistry of urban streams at 73 locations in the central districts in Wuhan during May 2019. Maps of isotopic signatures reflected a non-free-flowing state in part of the urban stream system in Wuhan. A lower DO and a higher EC level were found in urban streams relative to the adjacent Yangtze River. The Na+, K+, and Cl- concentrations in urban streams were > 3.0 times as high as those in the Yangtze River, and there was a slight increasing trend between 1.1 and 1.4 times for other major ions. The mildly elevated Fe concentration (1.3 times) and markedly elevated Mn concentration (> 5.0 times) were observed in urban streams. Spearman's correlation analysis indicated strong positive bivariate correlations among Na+, K+, and Cl- in urban streams, and an urban geochemical principal component was identified by principal component analysis. Plotting Na/(Na + Ca) versus total dissolved solids (TDS) indicated a potential risk of "urban stream syndrome." These findings can enhance the knowledge of anthropogenic impacts on current urban stream water quality and provide reference for the restoration and improvement of water ecology functions of the urban stream system in Wuhan.


Neighbourhood effects on psychotic and depressive symptoms in the context of religious sectarianism in Northern Ireland: A data linkage study.
The incidence of psychotic disorders is higher in ethnic minorities groups. The 'ethnic density effect', in which living in a neighbourhood with a low own-group proportion increases the risk of psychosis, is one explanatory factor. The density effect in the ethno-religious and sectarian context of Northern Ireland has been found to be reversed, particularly for Catholics, in which there is harmful effect of high own-group density areas. This is partly explained by high urbanicity, deprivation and unemployment, but is otherwise not well understood. This study aimed to examine the density effect at the level of symptomology (positive and negative psychosis symptoms and depressive symptoms) in a representative sample of people with a first episode of psychosis in Northern Ireland. Data linkage methodology was used drawing on data from the Northern Ireland First Episode Psychosis Study (NIFEPS) and the 2001 Census of Northern Ireland. In total, 223 people between the ages of 18 to 64 were included in the study. A significant density effect was found for Catholics for total psychosis scores, but not for positive, negative and depressive symptoms, nor for general psychopathology, after adjusting for individual and area characteristics. The model accounted for just over 12% of the variance. No effect was found for Protestants. The findings suggest that the density effect for Catholics is unrelated to the core features of psychosis (hallucinations, delusions and anhedonia) but rather to broader cognitive and emotional disturbances and area deprivation. Explanations of exposure to social adversity and inequality are proposed, with implications for public mental health and social policy.


A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene diphosphonate in patients with moderate to severe rheumatoid arthritis.
Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088.


Rate of regeneration of sensory axons in transected rat sciatic nerve repaired with epineurial sutures.
Rat sciatic nerves were cut and the ends were rejoined using epineurial sutures. The most rapidly regenerating sensory axons, as measured by the pinch test, grew at a rate of 3.2 +/- 0.2 (SE) mm/day after a delay of 4.0 +/- 0.3 (SE) days. Regenerating axons began to grow beyond the site of injury about 2 days later in sutured nerves than in crushed nerves; this difference provides an estimate of the scar delay in sutured nerves. The rate of axonal outgrowth was slower in sutured nerves than in crushed nerves throughout the distal stump.


Benefits of electronic pillboxes in evaluating treatment compliance of patients with mild to moderate hypertension.
This study was designed to assess the compliance of hypertensive patients with a once-daily regimen of the angiotensin converting enzyme (ACE) inhibitor trandolapril and to evaluate the antihypertensive efficacy of the drug in relation to the time interval between taking the final dose and measuring the blood pressure (BP). After a 2-week wash-out period, hypertensive patients, recruited by cardiologists, received trandolapril 2 mg once daily in the morning for 4 weeks. In order to assess compliance, each patient's supply of trandolapril capsules was presented in a pillbox that incorporated in its lid a microprocessor that recorded the date and time of each occasion that it was opened. BP was measured using validated semi-automatic devices, at the end of both the wash-out and the treatment period. A total of 590 patients entered the study. Compliance data were evaluable for 501 patients. Overall compliance, defined as the ratio of the number of openings recorded to the number of doses prescribed was less than 80, 80-100, and more than 100% in 17, 63 and 20% of patients, respectively. The average number (+/- SD) of missed doses was 4.5 +/- 8 (median 2). The average interval between successive openings was 25 h 07 min mean +/- 13 h (median 24 h). The average number of delayed doses (a delayed dose being defined as the box being opened 25-36 h after the previous occasion) was 5.6 +/- 3 (median 6). Patients living in the Paris area had more forgotten and delayed doses than those living in the provinces (7.9 versus 3.8 forgotten; P<0.0001 and 6.3 versus 5.5 delayed; P<0.005). Doses were forgotten and delayed more often during weekends than on weekdays. The greatest number of delayed doses occurred in those patients under 60 years of age (6.0 versus 5.2; P<0.01). Decreases in systolic blood pressure (SBP and diastolic blood pressure (DBP) were 20.3/12.8 mmHg, for patients whose final drug was taken on the same day as the BP measurement, and 18.9/11.2 mmHg for patients whose final dose was taken on the previous day. Electronic compliance monitoring allows refined analysis of the behaviour of hypertensive patients. In this study doses were missed and delayed frequently during the first month of treatment, depending on the patient's lifestyle.


Complete Genome Sequence of Pseudomonas aeruginosa Reference Strain PAK.
We report the complete genome of Pseudomonas aeruginosa strain PAK, a strain which has been instrumental in the study of a range of P. aeruginosa virulence and pathogenesis factors and has been used for over 50 years as a laboratory reference strain.


Knowledge of preconception care and its association with family planning utilization among women in Ethiopia: meta-analysis.
Preconception care (PCC) increases the chance of couple's being healthy and having a healthier baby. It is an important strategy to prevent maternal and perinatal complications. The level of knowledge on preconception care increases its uptake. It is also considered as an input for further intervention of reduction in maternal and neonatal mortality enabling progress towards sustainable development goals (SDGs). Therefore, this systematic review and meta-analysis aimed to estimate the pooled knowledge level of PCC and its association with family planning usage among women in Ethiopia. All observational studies regardless of publication status were retrieved. Important search terms were used to search articles in Google scholar, African Journals Online, CINHAL, HINARI, Science Direct, Cochrane Library, EMBASE, and PubMed/Medline. Independent critical appraisal of retrieved studies was done using the Newcastle-Ottawa assessment checklist. The meta-analysis was conducted using STATA version 14 software. The I2 statistics were used to test heterogeneity, whereas publication bias was assessed by Begg's and Egger's tests. The results of the meta-analysis were explained in the Odds ratio (OR) with a 95% confidence interval (CI) and presented using forest plots. A total of seven articles were included in the current systematic review and meta-analysis. Based on the data retrieved from the articles, 35.7% of women in Ethiopia had good knowledge about preconception care. The subgroup analysis based on region revealed the lowest (22.34%) and highest (45.06%) percentage of good knowledge on preconception care among women who were living in Amhara and Oromia regions, respectively. Moreover, women who utilized family planning services were three and more times (OR 3.65 (95% CI 2.11, 6.31)) more likely to have a good level of knowledge about preconception care. One-third of Ethiopian women had good knowledge about preconception care. Family planning utilization had a positive impact on women's knowledge of preconception care.


Genomic and Metabolic Insights into Two Novel Thiothrix Species from Enhanced Biological Phosphorus Removal Systems.
Two metagenome-assembled genomes (MAGs), obtained from laboratory-scale enhanced biological phosphorus removal bioreactors, were analyzed. The values of 16S rRNA gene sequence identity, average nucleotide identity, and average amino acid identity indicated that these genomes, designated as RT and SSD2, represented two novel species within the genus Thiothrix, 'Candidatus Thiothrix moscowensis' and 'Candidatus Thiothrix singaporensis'. A complete set of genes for the tricarboxylic acid cycle and electron transport chain indicates a respiratory type of metabolism. A notable feature of RT and SSD2, as well as other Thiothrix species, is the presence of a flavin adenine dinucleotide (FAD)-dependent malate:quinone oxidoreductase instead of nicotinamide adenine dinucleotide (NAD)-dependent malate dehydrogenase. Both MAGs contained genes for CO2 assimilation through the Calvin-Benson-Bassam cycle; sulfide oxidation (sqr, fccAB), sulfur oxidation (rDsr complex), direct (soeABC) and indirect (aprBA, sat) sulfite oxidation, and the branched Sox pathway (SoxAXBYZ) of thiosulfate oxidation to sulfur and sulfate. All these features indicate a chemoorganoheterotrophic, chemolithoautotrophic, and chemolithoheterotrophic lifestyle. Both MAGs comprise genes for nitrate reductase and NO-reductase, while SSD2 also contains genes for nitrite reductase. The presence of polyphosphate kinase and exopolyphosphatase suggests that RT and SSD2 could accumulate and degrade polyhosphates during the oxic-anoxic growth cycle in the bioreactors, such as typical phosphate-accumulating microorganisms.


Radioligand binding to muscarinic receptors of bovine aortic endothelial cells.
1. Muscarinic receptors on endothelial cells of bovine thoracic aorta were characterized by binding assays in which (-)-[3H]-N-methyl quinuclidinyl benzilate ([3H]-NMeQNB) was used as radioligand. 2. Binding of [3H]-NMeQNB to crude membranes of freshly isolated endothelial cells was atropine-displaceable and of high affinity (KD = 0.48 nM) to a single class of sites (maximum binding capacity: 14 +/- 3 fmol mg-1 protein). Stereospecificity of the binding sites was demonstrated in experiments in which [3H]-NMeQNB binding was inhibited by dexetimide in the nanomolar range (KI = 0.63 nM) and by levetimide, its stereoisomer in the micromolar range (KI = 3.2 microM) (selectivity factor: approximately 5000). 3. Drug competition curves indicated a single class of binding sites for antagonists and the following apparent affinities (KI, nM): methyl atropine: 1.1: 4-diphenylacetoxy N-methyl piperidine methyl bromide (4-DAMP): 3.4; pirenzepine: 16; 11-[2-diethylamino-methyl)-1-piperidinyl- acetyl]-5,11-dihydro-6H-pyrido(2,3-b)1,4-benzodiazepine-6-one (AF-DX 116); 2.500. Competition of acetylcholine with [3H]-NMeQNB was best described by two affinity sites (or states) (KH = 0.82 microM, KL = 1.6 microM). In the presence of guanylimido diphosphate [Gpp(NH)p] (100 microM), acetylcholine affinity (IC50) was slightly, but significantly reduced (factor approximately 4). 4. Binding of [3H]-NMeQNB to freshly harvested intact cells was also atropine-displaceable, stereospecific (selectivity factor: approximately 3500) and of high affinity (KD = 0.35 nM). The maximum binding capacity (9 +/- 2 fmol mg-1 total cell protein) was comparable to that of membranes and corresponded to approximately 900 binding sites per endothelial cell. Binding to enzymatically harvested and cultured endothelial cells, or membranes derived therefrom, showed no atropine-displaceable binding. 5. The results suggest that (1) bovine aortic endothelial cells contain muscarinic binding sites with all necessary criteria of functional muscarinic receptors; (2) the receptor most closely corresponds to the M1 subtype and is of comparatively very low density, and (3) cultured endothelial cells lose their receptors during isolation or culture procedures.


Laser Microdissection of Woody and Suberized Plant Tissues for RNA-Seq Analysis.
An accurate profile of gene expression at a cellular level can contribute to a better understanding of biological processes and complexities involved in regulatory mechanism of woody plants. Laser microdissection is one technique that allows isolation of specific, target cells or tissue from a heterogeneous cell population. This technique entails microscopic visualization of the selected tissue and use a laser beam to separate the desired cells from surrounding tissue. Initial identification of these cells is made based on morphology and/or histological staining. Some works have been made in several tissues and plant models. However, there are few studies of laser microdissection application in woody species, particularly, lignified and suberized cells. Moreover, the presence of high level of suberin in cell walls can be a big challenge for the application of this approach. In our study it was developed a technique for tissue isolation, using laser microdissection of four different plant cell types (phellogen, lenticels, cortex and xylem) from woody tissues of cork oak (Quercus suber), followed by RNA extraction and RNA-Seq. We tested several methodologies regarding laser microdissection, cryostat equipments, fixation treatments, duration of single-cells collection and number of isolated cells by laser microdissection and RNA extraction procedures. A simple and efficient protocol for tissue isolation by laser microdissection and RNA purification was obtained, with a final method validation of RNA-Seq analysis. The optimized methodology combining RNA-Seq for expression analysis will contribute to elucidate the molecular pathways associated with different development processes of the xylem and phellem in oaks, including the lenticular channels formation.


A one-stage combined approach for the management of large cerebellopontine angle tumors.
This paper reviews 180 cerebellopontine angle lesions in regard to results and complications of the surgical management with special emphasis on the diagnosis, surgical removal, and results in 60 large (4 cm. or greater) tumors of the CPA. The authors conclude that in their experience a one-stage combined translabyrinthine-suboccipital approach, which is explained in detail, is the procedure of choice in dealing with large tumors of the CPA.


Management of knee rheumatoid arthritis and tibia nonunion with one-stage total knee arthroplasty and intramedullary nailing: A report of two cases.
Total knee arthroplasty (TKA) is a surgical procedure which is widely used in the treatment of gonarthrosis secondary to rheumatoid arthritis (RA). The incidence of stress fractures in tibia in the patients with RA is higher compared to normal patients. In this study, we report two cases of TKA and intramedullary nailing in RA patients with severe knee arthritis and tibial nonunion. Both patients had a satisfactory clinical outcome with radiological healing of the tibial fracture.


Preclinical and clinical studies with latex from Ficus glabrata HBK, a traditional intestinal anthelminthic in the Amazonian area.
Ficus glabrata latex has been a well-known anthelminthic remedy in the neotropical regions since ancient times. The latex has been commercially exploited for decades because of its content of the proteolytic enzyme-complex ficin. A safe dosage regimen with direct use of the latex has been elucidated to control intestinal helminthiasis in the Indian and non-Indian rural population. Helminthiasis was common in three Amazonian villages, field bases for the clinical study, with an overall prevalence of 92%. Specific prevalences were: Ascaris 68%, Strongyloides 42%, Trichuris 41%, Ancylostoma/Necator 26% and Taenia 1%. Variation in the biological activity of the latex was estimated by using a milk coagulating test. Pharmacological studies with live Ascaris demonstrated a lethal effect at concentrations down to 0.05% latex in physiological saline solution. A clinical trial on 181 persons has resulted in a recommended dosage of 1.0 cm3 of prepared latex/kg per day for 3 days to be repeated every 3 months.


HIF-1alpha overexpression and experimental murine atherosclerosis.
Lymphocytes play an important role in the progression of atherosclerosis. Recently, hypoxia inducible factor-1 (HIF-1) was found to attenuate inflammation by regulating T cell activation and cytokine production. We studied the effects of overexpression of HIF-1alpha in ApoE knockout murine lymphocytes, on experimental atherosclerosis. ApoE-/- mice were submitted to intravenous hydrodynamic injection of empty plasmid or HIF-1alphaP564A (HIF-1alpha mutated stabilized construct). Robust expression of HIF-1alpha was evident in spleen cells of recipient animals. Increased expression of IL-10 as well as decreased expression of IFN-gamma was measured in splenocytes of HIF-1alpha-treated mice by RT-PCR. One week postinjection, antibody array analysis revealed a pattern consistent with a T helper 1 to T helper 2 shift. On sacrifice, assessment of aortic sinus lesions revealed a significant reduction in plaque size in HIF-1alpha injected mice. A reduced expression of IFN-gamma was evident in CD4+ spleen-derived lymphocytes and aortas of HIF-1alpha-injected mice. HIF-1alpha expression in mouse lymphocytes is associated with a reduced IFN-gamma expression and attenuation of experimental atherosclerosis.


Addressing the challenge of in situ structural studies of RNP granules in light of emerging opportunities.
The emerging concept of phase separation in cell biology postulates that, in concert with the classical structural view of stoichiometric quaternary complexes, ribonucleoproteins (RNPs) and nucleic acids are intricately involved in the formation of meso-scale membraneless compartments, commonly termed RNP granules. Elucidating the structural basis underlying such non-deterministic assemblies remains challenging due to their inherent compositional heterogeneity, conformational flexibility and biophysical dynamics. Techniques which allow characterization of their molecular architectures, ideally within the native cellular environment, are therefore required. We review advances in in situ methods that can provide data on the molecular organization in RNP granules from the level of amino-acid interactions, up to their complex cross-talk in cells. These data combined into integrative modeling and multi-scale simulation frameworks will provide an understanding of RNP granules on a continuum scale of spatial resolutions to elucidate their structure-dynamics-function relations.


Azacoccones F-H, new flavipin-derived alkaloids from an endophytic fungus Epicoccum nigrum MK214079.
Three new flavipin-derived alkaloids, azacoccones F-H (1-3), along with six known compounds (4-9) were isolated from the endophytic fungus Epicoccum nigrum MK214079 associated with leaves of Salix sp. The structures of the new compounds were established by analysis of their 1D/2D nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectroscopy (HRESIMS) data. The absolute configuration of azacoccones F-H (1-3) was determined by comparison of experimental electronic circular dichroism (ECD) data with reported ones and biogenetic considerations. Epicocconigrone A (4), epipyrone A (5), and epicoccolide B (6) exhibited moderate antibacterial activity against Staphylococcus aureus ATCC 29213 with minimal inhibitory concentration (MIC) values ranging from 25 to 50 μM. Furthermore, epipyrone A (5) and epicoccamide A (7) displayed mild antifungal activity against Ustilago maydis AB33 with MIC values of 1.6 and 1.8 mM, respectively. Epicorazine A (8) showed pronounced cytotoxicity against the L5178Y mouse lymphoma cell line with an IC50 value of 1.3 μM.


Synthesis and evaluation of two novel 2-nitroimidazole derivatives as potential PET radioligands for tumor imaging.
Nitroimidazole (azomycin) derivatives labeled with radioisotopes have been developed as cancer imaging and radiotherapeutic agents based on the oncological hypoxic mechanism. By attaching nitroimidazole core with different functional groups, we synthesized new nitroimidazole derivatives and evaluated their potentiality as tumor imaging agents. Starting with commercially available 2-nitroimidazole, 2-fluoro-N-(2-(2-nitro-1H-imidazol-1-yl)ethyl)acetamide (NEFA, [(19)F]7) and 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl 2-fluoroacetate (NEFT, [(19)F]8), as well as radiolabeling precursors, the bromo-substituted analogs were quickly synthesized through a three-step synthetic pathway. The precursors were radiolabeled with [(18)F]F(-)/18-crown-6/KHCO(3) in dimethyl sulfoxide at 90°C for 10 min followed by purification with an Oasis HLB cartridge. Biodistribution studies were carried out in EMT-6 tumor-bearing mice. The uptake (%ID/g) in tumors and normal tissues were measured at 30 min postinjection. Liquid chromatography-electrospray ionization mass spectrometry (LC/MS) was used to distinguish metabolites from parent drugs in urine and plasma of rat injected with "cold" NEFA ([(19)F]7) and NEFT ([(19)F]8). Two radiotracers, [(18)F]NEFA ([(18)F]7) and [(18)F]NEFT ([(18)F]8), were prepared with average yields of 6%-7% and 9%-10% (not decay corrected). Radiochemical purity for both tracers was >95% as determined by HPLC. Biodistribution studies in EMT-6 tumor-bearing mice indicated that the tumor to blood and tumor to liver ratios of both [(18)F]7 (0.96, 0.61) and [(18)F]8 (0.98, 1.10) at 30 min were higher than those observed for [(18)F]FMISO (1) (0.91, 0.59), a well-investigated azomycin-type hypoxia radiotracer. Liquid chromatography-electrospray ionization mass spectrometry analysis demonstrated that fluoroacetate was the main in vivo metabolite for both NEFA ([(19)F]7) and NEFT ([(19)F]8). In this research, two new fluorine-18 labeled 2-nitroimidazole derivatives, [(18)F]7 and [(18)F]8, both of which containing in vivo hydrolyzable group, were successfully prepared. Further biological evaluations are warranted to investigate their potential as PET radioligands for imaging tumor.


Bone mass in young patients with type I diabetes.
We measured bone mineral content (BMC) with single photon absorptiometry in two groups of young patients with type I diabetes: the first group (prospective study) consists of 48 patients followed from onset to the third year of diabetes and the second group (cross-sectional study) consists of 66 long-term diabetics. Bone mineral content at onset of disease was lower than normal in only two cases. After 3 years of diabetes no male revealed BMC below the normal range but two females (6.6%) had low BMC values. In our cross-sectional study we found a BMC reduction in 12% of the cases. We did not find a relationship between bone deficit and duration of diabetes, or bone mass values and HbA1.


Refining competition in the self-organising tree map for unsupervised biofilm image segmentation.
The Self Organising Tree Map (SOTM) neural network is investigated as a means of segmenting micro-organisms from confocal microscope image data. Features describing pixel and regional intensities, phase congruency and spatial proximity are explored in terms of their impact on the segmentation of bacteria and other micro-organisms. The significance of individual features is investigated, and it is proposed that, within the context of micro-biological image segmentation, better object delineation can be achieved if certain features are more dominant in the initial stages of learning. In this way, other features are allowed to become more/less significant as learning progresses: as more knowledge is acquired about the data being segmented. We argue that the efficiency and flexibility of the SOTM in adapting to, and preserving the topology of input space, makes it an appropriate candidate for implementing this idea. We propose a refinement to the competitive search strategy that allows for a more appropriate fusion of signal and proximal features, thereby promoting a segmentation that is more sensitive to the regional associations of different microbial matter. A refined stop criterion is also suggested such that the dynamically generated number of classes becomes more data dependant. Preliminary experiments are presented and it is found that favouring intensity characteristics in the early phases of learning, whilst relaxing proximity constraints in later phases of learning, offers a general mechanism through which we can improve the segmentation of microbial constituents.


Cytogenetic and molecular predictors of outcome in acute lymphocytic leukemia: recent developments.
During the last decade a tremendous technologic progress based on genome-wide profiling of genetic aberrations, structural DNA alterations, and sequence variations has allowed a better understanding of the molecular basis of pediatric and adult B/T-acute lymphoblastic leukemia (ALL), contributing to a better recognition of the biological heterogeneity of ALL and to a more precise definition of risk factors. Importantly, these advances identified novel potential targets for therapeutic intervention. This review will be focused on the cytogenetic/molecular advances in pediatric and adult ALL based on recently published articles.


Breaking bad news: experiences and preferences of advanced cancer patients at a Portuguese oncology centre.
The disclosure of information to patients about diagnosis and prognosis and other aspects of care is still a matter of debate. We have conducted a study in advanced cancer patients about their experiences and preferences concerning this issue. A questionnaire was developed and completed during the first appointment in the outpatient clinic of an oncology centre's palliative care unit, before the patient had any contact with the staff of the unit. The study was conducted on a convenience sample of 47 patients. We found that 34 (72%) of those patients thought they had been informed of their diagnosis, most of them by the hospital doctor. However, not all stated the diagnosis in a manner clearly showing that they were aware of the nature of their disease. Most patients were with a family member when the diagnosis was disclosed, which is what the majority had preferred. Of the 13 uninformed patients, only one preferred to remain uninformed. Most patients (89%) participated in decisions concerning treatment, although only 68% thought they should have participated. Some 39 patients (83%) were informed that they were being referred to the palliative care unit, but surprisingly only eight had received an explanation of the unit's function. We concluded that, although most patients had been informed of their disease, there remains many problems, the most important of which, in our view, is the difference between the information provided and the patients' needs.


Theory for tailoring sonic devices: diffraction dominates over refraction.
Acoustic crystal devices, with dimensions on the order of several wavelengths, are studied by using the finite-difference time domain method in the moderately long wavelength propagation regime. From the focusing and imaging process performed by a square shaped lens, it is shown that diffractive effects dominate over those due to refraction. The major role of the device edge diffraction is shown by means of the well known Babinet principle. The first examples of imaging with a sonic plane lens, both with crystal structure and massive, and with an acoustic prism able to change the propagation direction of a plane wave, are presented.


Hip Arthroscopic Reduction and Fixation for Adolescent Acetabular Posterior Wall Fracture: A Case Report.
Posterior wall fracture is the most common type of acetabular fracture, the traditional open reduction and fixation through the Kocher-Langenbeck approach required a large incision and extensive muscle and soft tissue dissection, resulting in more blood loss, more complications and delayed recovery after the operation. Hip arthroscopy has been widely used in clinical practice but rarely reported in acetabular fractures. We present the case of a 14-year-old boy with acetabular posterior wall fracture who was treated with hip arthroscopy reduction and fixation using anchors. He began to walk with partial weight-bearing assisted by double crutches, and returned to school with crutches at 3 days after surgery. Although hip arthroscopy is technically more demanding, it's an optimal choice for selected patients of acetabular fracture with the advantages of less invasive and faster postoperative recovery.


Do primary afferents from tooth-pulp cross the midline?
Compound action potentials were recorded from the pulps of canine teeth in cats during stimulation of the inferior dental nerve, trigeminal ganglion or brain stem on one side. Recordings were also made from the inferior dental nerve while stimulating the canine pulps. No evidence for pulpal fibres crossing the midline was found.


Evidence for an altered dopamine beta-hydroxylase activity in migraine and tension-type headache.
Sympathetic dysfunction is often present in migraine. It has been suggested that serum dopamine-beta-hydroxylase (D beta H) can be taken as an index of peripheral sympathetic activity. We studied the serum D beta H activity in migraine with and without aura and in tension-type headache patients compared with healthy control subjects. The serum D beta H activity was significantly lower in migraine and tension-type headache patients than in the control group. No significant difference was observed among the three groups of patients studied. These findings suggest that patients with migraine and tension-type headache have a sympathetic hypofunction that may play an important role in the pathogenesis.


Highly sensitive detection of organophosphorus pesticides by acetylcholinesterase-coated thin film bulk acoustic resonator mass-loading sensor.
An acetylcholinesterase-coated thin film bulk acoustic resonator has been developed for the detection of organophosphorus pesticides. The thin film bulk acoustic resonator acts as a robust mass-sensitive transducer for bio-sensing. This device works in thickness shear mode with a resonance at 1.97 GHz. The detection is based on the inhibitory effects of organophosphorus compounds on the enzymatic activity of the acetylcholinesterase immobilized on one of the faces of the acoustic resonator. The enzyme reaction in the substrate solution and the inhibitory effect is observed are real time by measuring the frequency shift. The presence of organophosphorus pesticides can be detected from the diminution of the frequency shift compared with the levels found in their absence. The device exhibits linear responses, good reproducibility, simple operation, portability and a low detection limit of 5.3×10(-11) M for paraoxon. The detection results of organophosphorus pesticide residues in practical samples show that the proposed sensor has the feasibility and sensing accuracy comparable to gas chromatography.


Overexpression of Fto leads to increased food intake and results in obesity.
Genome-wide association studies have identified SNPs within FTO, the human fat mass and obesity-associated gene, that are strongly associated with obesity. Individuals homozygous for the at-risk rs9939609 A allele weigh, on average, ~3 kg more than individuals with the low-risk T allele. Mice that lack FTO function and/or Fto expression display increased energy expenditure and a lean phenotype. We show here that ubiquitous overexpression of Fto leads to a dose-dependent increase in body and fat mass, irrespective of whether mice are fed a standard or a high-fat diet. Our results suggest that increased body mass results primarily from increased food intake. Mice with increased Fto expression on a high-fat diet develop glucose intolerance. This study provides the first direct evidence that increased Fto expression causes obesity in mice.


Long-term prognosis of infants with idiopathic respiratory distress syndrome. Follow-up studies in infants surviving after the introduction of continuous positive airway pressure.
Fifty-one children surviving IRDS with CPAP alone or CPAP and IPPV were studied at the age of 2.5 to 4.0 years. One child had developed tetraplegia and mental retardation and 6 children were speech-retarded. Correlation with perinatal events showed that this group of children had a significantly lower gestational age and birth weight, a lower Apgar score and a higher PCO2 prior to ventilatory treatment than the remainder. Re-examination by age 4.0 to 5.0 years showed persistent handicaps in only four of the seven children.


Long-term outcomes of Roux-en-Y gastric bypass or sleeve gastrectomy in patients with cirrhosis; before, during or after liver transplantation: A single center's experience.
The increasing prevalence of morbid obesity (MO) results in parallel growth of obesity-associated liver diseases necessitating liver transplantation (LT). To examine the feasibility and safety of Roux-en-Y gastric bypass or sleeve gastrectomy in the setting of LT. This retrospective chart review included the data on all the MO candidates before and after LT who underwent bariatric surgery (BS) in our institution between 04/2013-09/2016. The reported outcomes were weight change and early and late postoperative complications (mean follow-up: 43 ± 11.1 months). Eighteen MO peri-LT patients (10 females, 8 males, average age 48 years) were included in the study. Ten had cirrhosis (mean Model of End-stage Liver Disease [MELD] score of 12.5 ± 6.42), three underwent concurrent LT and BS (mean MELD score 23.7 ± 0.58), and five had LT (mean of 56 months from LT). The mean percentage of total and excess weight loss was 31% and 81%, respectively. Six of the eight patients with type 2 diabetes mellitus became normoglycemic after BS. Three patients sustained perioperative complications. Two cirrhotic patients died 1 and 4.5 years after BS with decompensation. Bariatric surgery appears to effectively address obesity in cirrhotic and LT patients. The surgical risk is higher than that of the regular BS population.


Control of superoxide and nitric oxide formation during human sperm capacitation.
We studied the modulation of superoxide anion (O(2).(-)) and nitric oxide (NO.) generation during human sperm capacitation (changes needed for the acquisition of fertility). The production of NO. (diaminofluorescein-2 fluorescence assay), but not that of O(2).(-) (luminescence assay), related to sperm capacitation was blocked by inhibitors of protein kinase C, Akt, protein tyrosine kinase, etc., but not by those of protein kinase A. Extracellular calcium (Ca(2+)) controlled O(2).(-) synthesis but extra- and intracellular Ca(2+) regulated NO. formation. Zinc inhibited capacitation and formation of O(2).(-) and NO.. Zinc chelators (TPEN and EDTA) and sulfhydryl-targeted compounds (diamide and N-ethylmaleimide) stimulated capacitation and formation of O(2).(-) and NO.; superoxide dismutase (SOD) and nitric oxide synthase inhibitor (L-NMMA) prevented these events. Diphenyliodonium (flavoenzyme inhibitor) blocked capacitation and related O(2).(-) synthesis but promoted NO. formation, an effect canceled by SOD and L-NMMA. NADPH induced capacitation and NO. (but not O(2).(-)) synthesis and these events were blocked by L-NMMA and not by SOD. Integration of these data on O(2).(-) and NO. production during capacitation reinforces the concept that a complex, but flexible, network of factors is involved and probably is associated with rescue mechanisms, so that spermatozoa can achieve successful fertilization.


The role of epithelial tight junctions involved in pathogen infections.
Tight junctions (TJs) are sealing complexes between adjacent epithelial cells, functioning by controlling paracellular passage and maintaining cell polarity. These functions of TJs are primarily based on structural integrity as well as dynamic regulatory balance, indicating plasticity of TJ in response to external stimuli. An indispensable role of TJs involved in pathogen infection has been widely demonstrated since disruption of TJs leads to a distinct increase in paracellular permeability and polarity defects which facilitate viral or bacterial entry and spread. In addition to pathological changes in TJ integrity, TJ proteins such as occludin and claudins can either function as receptors for pathogen entry or interact with viral/bacterial effector molecules as an essential step for characterizing an infective stage. This suggests a more complicated role for TJ itself and especially specific TJ components. Thus, this review surveys the role of the epithelial TJs involved in various pathogen infections, and extends TJ targeted therapeutic and pharmacological application prospects.


Wear Kinetics of Highly Cross-Linked and Conventional Polyethylene Are Similar at Medium-term Follow-Up After Primary Total Hip Arthroplasty.
Wear debris is a major factor in aseptic loosening of total hip arthroplasty. Ultra high molecular weight polyethylene inlays are known for significant wear, and the following generation, highly cross-linked polyethylene (HCLPE), has shown promising in vitro and short-term in vivo results. This study aimed to investigate wear debris of HCLPE liners with ceramic heads after 9 years to reveal the in vivo wear kinetics of this common bearing combination. Fifty-seven patients (72 hips; 46.5 ± 15.5 years; range 16-76 years) who underwent hip arthroplasty with an HCLPE liner (28- or 32-mm Biolox forte ceramic head) were followed up (mean 9.1 ± 2.4 years; range 3.9-13.8 years). Conventional anteroposterior X-rays were analyzed using Hip Analysis Suite software. Volumetric wear had a mean of 38.67 ± 22.09 mm3/year, 333.08 ± 183.93 mm3 overall, and linear wear was 0.063 ± 0.03 mm/year and 0.546 ± 0.27 mm overall. Male patients had a significantly higher wear rate (46.42 ± 27.68 mm3/year) and total wear (400.71 ± 235.21 mm3). Larger femoral heads had a significantly higher wear rate (43.10 ± 23.93 mm3/year) and total wear (364.23 ± 203.68 mm3). Regression analysis showed a significant cubic relationship (R2 = 0.307) with increasing yearly wear after approximately 108 months postoperatively. HCLPE liners show significant in vivo wear after 9 years. While the total wear compared to ultra high molecular weight polyethylene liners was decreased, the wear kinetics show a comparable course. The increase in wear rate after only 108 months postoperatively is especially alarming. Longer term follow-up is needed to distinguish the long-term superiority of HCLPE liners in polyethylene-ceramic paired hip arthroplasty.


Ameloblastoma ex calcifying odontogenic cyst (dentinogenic ghost cell tumor).
Calcifying odontogenic cyst (COC) has shown to be of extensive diversity in its clinical and histopathological features, as well as in its biological behavior. In this report, a rare case is described of ameloblastoma ex COC (dentinogenic ghost cell tumor) and the relevant literature is briefly reviewed.


The advanced adenoma as the primary target of screening.
The advanced adenoma bridges benign and malignant states and may be the most valid neoplastic surrogate marker for present and future colorectal cancer risk. We define the advanced adenoma as an adenoma with significant villous features (>25%), size of 1.0 cm or more, high-grade dysplasia, or early invasive cancer. Prevention studies should demonstrate a high efficacy in reducing the number of advanced adenomas. We should use the advanced adenoma in the evaluation of new screening technology, nutritional interventions, and chemoprevention agents because the advanced adenoma is a more desirable target for screening efficacy than is the more uncommon but life-threatening cancer stage or the more common but early, less significant small adenoma stage.


Investigating the Accumulation of Submicron Phase-Change Droplets in Tumors.
Submicron phase-change droplets are an emerging class of ultrasound contrast agent. Compared with microbubbles, their relatively small size and increased stability offer the potential to passively extravasate and accumulate in solid tumors through the enhanced permeability and retention effect. Under exposure to sufficiently powerful ultrasound, these droplets can convert into in situ gas microbubbles and thus be used as an extravascular-specific contrast agent. However, in vivo imaging methods to detect extravasated droplets have yet to be established. Here, we develop an ultrasound imaging pulse sequence within diagnostic safety limits to selectively detect droplet extravasation in tumors. Tumor-bearing mice were injected with submicron perfluorobutane droplets and interrogated with our imaging-vaporization-imaging sequence. By use of a pulse subtraction method, median droplet extravasation signal relative to the total signal within the tumor was estimated to be Etumor=37±5% compared with the kidney Ekidney=-2±8% (p < 0.001). This work contributes toward the advancement of volatile phase-shift droplets as a next-generation ultrasound agent for imaging and therapy.


A transgenic mouse for imaging caspase-dependent apoptosis within the skin.
Apoptosis is an essential process for the maintenance of normal physiology. The ability to noninvasively image apoptosis in living animals would provide unique insights into its role in normal and disease processes. Herein, a recombinant reporter consisting of beta-galactosidase gene flanked by two estrogen receptor regulatory domains and intervening Asp-Glu-Val-Glu sequences was constructed to serve as a tool for in vivo assessment of apoptotic activity. The results demonstrate that when expressed in its intact form, the hybrid reporter had undetectable beta-galactosidase activity. Caspase 3 activation in response to an apoptotic stimulus resulted in cleavage of the reporter, and thereby reconstitution of beta-galactosidase activity. Enzymatic activation of the reporter during an apoptotic event enabled noninvasive measurement of beta-galactosidase activity in living cells, which correlated with traditional measures of apoptosis in a dose- and time-dependent manner. Using a near-infrared fluorescent substrate of beta-galactosidase (9H-{1,3-dichloro-9,9-dimethylacridin-2-one-7-yl} beta-D-galactopyranoside), noninvasive in vivo imaging of apoptosis was achieved in a xenograft tumor model in response to proapoptotic therapy. Finally, a transgenic mouse model was developed expressing the ER-LACZ-ER reporter within the skin. This reporter and transgenic mouse could serve as a unique tool for the study of apoptosis in living cells and animals, especially in the context of skin biology.


Mosquito Control Based on Pesticides and Endosymbiotic Bacterium Wolbachia.
Mosquito-borne diseases, such as dengue fever and Zika, have posed a serious threat to human health around the world. Controlling vector mosquitoes is an effective method to prevent these diseases. Spraying pesticides has been the main approach of reducing mosquito population, but it is not a sustainable solution due to the growing insecticide resistance. One promising complementary method is the release of Wolbachia-infected mosquitoes into wild mosquito populations, which has been proven to be a novel and environment-friendly way for mosquito control. In this paper, we incorporate consideration of releasing infected sterile mosquitoes and spraying pesticides to aim to reduce wild mosquito populations based on the population replacement model. We present the estimations for the number of wild mosquitoes or infection density in a normal environment and then discuss how to offset the effect of the heatwave, which can cause infected mosquitoes to lose Wolbachia infection. Finally, we give the waiting time to suppress wild mosquito population to a given threshold size by numerical simulations.


Molecular characterization of multidrug-resistant ESKAPEE pathogens from clinical samples in Chonburi, Thailand (2017-2018).
ESKAPEE pathogens Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp. and Escherichia coli are multi-drug resistant (MDR) bacteria that present increasing treatment challenges for healthcare institutions and public health worldwide. 431 MDR ESKAPEE pathogens were collected from Queen Sirikit Naval Hospital, Chonburi, Thailand between 2017 and 2018. Species identification and antimicrobial resistance (AMR) phenotype were determined following CLSI and EUCAST guidelines on the BD Phoenix System. Molecular identification of antibiotic resistant genes was performed by polymerase chain reaction (PCR), real-time PCR assays, and whole genome sequencing (WGS). Of the 431 MDR isolates collected, 1.2% were E. faecium, 5.8% were S. aureus, 23.7% were K. pneumoniae, 22.5% were A. baumannii, 4.6% were P. aeruginosa, 0.9% were Enterobacter spp., and 41.3% were E. coli. Of the 401 Gram-negative MDR isolates, 51% were carbapenem resistant, 45% were ESBL producers only, 2% were colistin resistance and ESBLs producers (2%), and 2% were non-ESBLs producers. The most prevalent carbapenemase genes were blaOXA-23 (23%), which was only identified in A. baumannii, followed by blaNDM (17%), and blaOXA-48-like (13%). Beta-lactamase genes detected included blaTEM, blaSHV, blaOXA, blaCTX-M, blaDHA, blaCMY, blaPER and blaVEB. Seven E. coli and K. pneumoniae isolates showed resistance to colistin and carried mcr-1 or mcr-3, with 2 E. coli strains carrying both genes. Among 30 Gram-positive MDR ESKAPEE, all VRE isolates carried the vanA gene (100%) and 84% S. aureus isolates carried the mecA gene. This report highlights the prevalence of AMR among clinical ESKAPEE pathogens in eastern Thailand. E. coli was the most common MDR pathogen collected, followed by K. pneumoniae, and A. baumannii. Carbapenem-resistant Enterobacteriaceae (CRE) and extended spectrum beta-lactamases (ESBLs) producers were the most common resistance profiles. The co-occurrence of mcr-1 and mcr-3 in 2 E. coli strains, which did not affect the level of colistin resistance, is also reported. The participation of global stakeholders and surveillance of MDR remain essential for the control and management of MDR ESKAPEE pathogens.


Phantasy effects that which it represents.
This paper sets out to show that phantasy does not just inhabit a mental realm within the individual. With the help of some clinical examples, it tries to demonstrate that phantasy is itself an active agent, so that the image within the phantasy is brought into effect through a subtle stimulation of the social environment. The paper ends by suggesting the way in which this can happen.


Critical review of environmental impacts of microfibers in different environmental matrices.
Microfibers, as globally emerging environmental pollutants, have received increasing attention over recent years. In ecosystems, natural textile microfibers are the predominant fibers. The inadvertent ingestion of microplastics by organisms in an ecosystem provides a channel for microfibers to enter biological webs. Based on existing research on microfibers, this review summarizes the potential adverse impacts of microfibers on organisms living in marine, freshwater, and soil ecosystems, and provides a brief introduction to the source of microfibers, as well as the related current status and future challenges. Although previous studies have recorded the adverse effects of microfibers on ecosystems, there remains a lack of evidence on the toxic effects of microfibers on the primary producer level in food chains (e.g., phytoplankton). This is essential, as the long-term effects of microfiber toxicity on different ecosystems ultimately affect human health. The analysis of microfiber toxicity paves the way for the field of environmental research and provides future perspectives for researchers in the fields of ecotoxicology and microplastics.


Beyond equity: Advocating theory-based health promotion in parallel with COVID-19 mass vaccination campaigns.
Despite the challenges in managing the COVID-19 pandemic waves in different contexts and capacities, the vaccines that were recently approved for use have created a window of hope to fight this pandemic more effectively by achieving herd immunity. However, the rates of vaccination coverage vary considerably between countries. While looking at COVID-19 vaccination from a different perspective, it brings up the following question: is equitable vaccine delivery and access the only critical issue? Assessing facilitators and barriers to successful vaccination initiatives should be carefully considered and addressed by subsequent actions. The COVID-19 vaccination campaigns as part of disease prevention programs could be embedded in the core of theories for a more systematic approach to enhance vaccine acceptance among people. For effective implementation of public health programs, it is imperative to understand human health behaviours and to have sufficient knowledge about cultural and environmental influences. Sufficient and satisfactory COVID-19 vaccine uptake is not only challenged by the availability of vaccines or their distribution, but also by cultural and social norms in the community as well as the complexity of human behaviours. Therefore, the global efforts should target communities with theory-based health promotion and awareness programs in parallel with vaccination campaigns as a part of public health practice.


Multiple changes, multiple opportunities in the ambulatory surgery department.
As one facility that was restructured and purchased, the Ambulatory Surgery Department moved through changes at a very rapid pace. The waves of change began with preoperative testing requirements and expansion of the nurse's role in accurate and appropriate testing decisions. Cross-training for radiology, pain management, infusion services, and oncology services were also incorporated. As the department became a multi-faceted area of patient care, nursing staff met the challenge of change and grew both educationally and professionally. This article identifies areas of departmental and professional opportunity and outlines the development of protocols to meet each challenge.


Impact of increased collection rates and the use of commingled collection systems on the quality of recovered paper. Part 1: increased collection rates.
The recovery and utilization of recovered paper have increased over past decades all over the world due to economic, environmental, and social issues. However, it is well known that an extended recovered paper collection is detrimental to its quality, either by the exploitation of lower quality sources such as households, or the spreading of commingled systems instead of selective collection systems. The influence of these two factors was assessed by analyzing the quality of different recovered paper grades used as raw material in a mill located in Madrid (Spain) producing newsprint and light weight coated paper from recovered paper. Part 1 of the paper deals with the impact of increased collection rates on the quality of recovered paper and Part 2 with the use of commingled collection systems. Results of Part 1 show that increased collection rates have a large impact on the quality of the recovered paper. The quality, measured as total unusable material and moisture contents, had deteriorated very rapidly in only 4 years (2005-2008) as a consequence of increased collection rates. Collection rates increased in Spain from 58.5% to 68.6% during this period, resulting in more than 50% increase of total unusable material and 25% of moisture content. The downgrading of the quality of recovered paper is one of the major threats for extending the current limits of paper recycling. Therefore, future challenge is to increase its availability but maintaining its quality.


FOXP3, CBLB and ITCH gene expression and cytotoxic T lymphocyte antigen 4 expression on CD4(+) CD25(high) T cells in multiple sclerosis.
Expression of the forkhead box protein 3 (FoxP3) transcription factor is regulated by the E3 ubiquitin ligases Itch and Cbl-b and induces regulatory activity CD4(+) CD25(high) T cells. Treatment with interferon (IFN)-β enhances regulatory T cell activity in multiple sclerosis (MS). We studied the phenotype of CD4(+) CD25(high) T cells in MS by flow cytometry and its relationship with expression of the FOXP3, ITCH and CBLB genes. We found that untreated MS patients had lower cell surface expression of cytotoxic T lymphocyte antigen 4 (CTLA-4) on CD4(+) CD25(high) T cells and higher intracellular CTLA-4 expression than healthy controls. Cell surface expression of CTLA-4 on CD4(+) CD25(high) T cells correlated with expression of FOXP3 mRNA in untreated patients and increased significantly with time from most recent injection in patients treated with IFN-β. FOXP3 mRNA expression correlated with CBLB and ITCH and T helper type 2 cytokine mRNA expression in MS patients. These data link expression of FOXP3, CBLB and ITCH mRNA and CTLA-4 expression on the surface of CD4(+) CD25(high) T cell in MS. We hypothesize that this may reflect alterations in the inhibitory effect of CTLA-4 or in regulatory T cell function.


Chronic effects of amiodarone in patients with refractory ventricular tachycardia.
We examined the chronic electrophysiologic, systemic, and pharmacologic effects of chronic oral amiodarone therapy in 24 patients with refractory ventricular tachycardia and organic heart disease. Chronic amiodarone therapy resulted in significant increases in R-R interval (from 798 +/- 182 msec to 912 +/- 100 msec; P less than 0.01), P-R interval (from 205 +/- 66 msec to 221 +/- 87 msec; P less than 0.02), QRS duration (from 103 +/- 24 msec to 115 +/- 28 msec; P less than 0.001), and Q-Tc interval (from 413 +/- 48 msec to 470 +/- 46 msec; P less than 0.001). Significant increases were also noted in P-A interval (from 36 +/- 14 msec to 45 +/- 13 msec; P less than 0.05), A-H interval (from 119 +/- 61 msec to 141 +/- 87 msec; P less than 0.02), and H-V interval (from 52 +/- 12 msec to 64 +/- 11 msec; P less than 0.001). Electrophysiologic parameters showing changes included corrected sinus node recovery time (from 271 +/- 140 msec to 425 +/- 122 msec; P less than 0.01), the effective refractory period of the atrium (from 263 +/- 32 msec to 321 +/- 47 msec; P less than 0.01), the effective refractory period of the atrioventricular node (from 348 +/- 109 msec to 478 +/- 157 msec; P less than 0.001), the effective refractory period of the ventricle (from 253 +/- 21 msec to 291 +/- 28 msec; P less than 0.001), the atrial pacing cycle length producing A-V nodal Wenckebach (from 436 +/- 109 msec to 531 +/- 95 msec; P less than 0.001), and the functional refractory period of the A-V node (from 422 +/- 68 msec to 499 +/- 95 msec; P less than 0.001). Programmed electrical stimulation performed after 21-88 (mean 31) days of treatment was highly predictive of long-term results if suppression of arrhythmia induction was demonstrated (12 patients) or if the spontaneous arrhythmia was reinduced (5 patients). Induction of morphologically new ventricular tachyarrhythmias was frequent (42%) but had a low spontaneous recurrence rate (10%) during follow-up. Systemic parameters on chronic amiodarone therapy showed significant increases in total T4 and reverse T3, with no change in pulmonary function tests or left ventricular ejection fraction. Serum amiodarone levels at chronic electrophysiologic study ranged from 0.44-4.10 (mean 1.3) micrograms/ml. Long-term follow-up (2.5 to 20 months) demonstrated a marked improvement in clinical symptoms and mortality, but a significant recurrence rate of a well-tolerated slower arrhythmia persisted. Adverse effects on chronic amiodarone therapy were frequent (10 patients) and often disabling but required drug discontinuation in only 1 patient.


Fibroblast growth factor (FGF) levels in the developing rat brain.
Acidic and basic fibroblast growth factors (FGF) are polypeptides with potent multipotential trophic effects on central nervous system (CNS) glia, endothelial cells, and neurons. These factors are characterized by strong binding to heparin, and are commonly assayed by their mitogenic activity on Balb/c 3T3 cells in vitro. We found a marked (ca. 13-fold) increase in Balb/c 3T3 mitogenic activity in the developing rat brain from the embryonic stage to the third postnatal week. High levels were sustained in the mature brain. Most of the mitogenic activity from rat brain bound strongly to heparin-affinity columns, and was eluted at positions characteristic of acidic FGF (aFGF) and basic FGF (bFGF). The presence of aFGF and bFGF in eluted peaks was confirmed by immunoblotting techniques using specific anti-FGF sera. Heparin-affinity high performance liquid chromatography (HPLC) showed a proportionately greater increase in levels of aFGF than bFGF between the tenth and fortieth postnatal days. Increases in FGF levels during late embryonic and early postnatal stages of brain development may play an important role in the glial and capillary proliferation, as well as in the neuronal outgrowth and synapse formation that is occurring during this time. The differential rates of accumulation of aFGF vs bFGF suggest different physiological roles for these factors in the developing brain.


An ultrasonogram display system using a natural color scale.
The gray scale display used in B scan ultrasonography limits the perceptibility of clinically useful information. Presentation in color can increase perceptibility, but current color displays have no natural scale and may have the fault of a discrete color spectrum. The continuous heated-object color spectrum solves these problems. To produce a display using this spectrum, we have built an inexpensive system to adapt the scan converter output of a gray scale ultrasonograph to a commercial color television.


The glucose metabolism disorder and dyslipidemia among girls with different phenotype polycystic ovary syndrome.
This study aimed to determine the prevalence of glucose metabolism disorder and dyslipidemia in 14-18-year-old girls with different phenotype polycystic ovary syndrome (PCOS). This descriptive, cross-sectional study was conducted on 3200 high-school adolescents aged 14-18 years in Shiraz in 2010. Selected parameters of metabolic syndrome (fasting blood glucose, glucose tolerance test [GTT], insulin level, triglyceride (TG), cholesterol, and high-density lipoprotein [HDL]), based on adult treatment panel Ш definition criteria, were compared between the "PCOS" and control groups. Results were compared at four main phenotypes. The level of serum TG was increased in the Phenotype B (P = 0.03) and Phenotype D (P = 0.01), compared to the control group. Cholesterol and low-density lipoprotein levels (P < 0.05) and GTT (P > 0.05) were increased, and HDL was decreased (was below 50) in all the four phenotypes and the control group (P > 0.05). The risk of metabolic alterations of glucose metabolism disorder and dyslipidemia in PCOS adolescents was more than non-PCOS counterparts.


Systematic review: anti-viral therapy of recurrent hepatitis C after liver transplantation.
Hepatitis C virus (HCV) infection is the first cause of liver transplantation worldwide. Recurrence of infection is constant, and compromises patient and graft survival. To provide an updated review of the main treatments of recurrent HCV. MEDLINE (1990 to August 2010) and national meeting abstract search. Search terms included hepatitis C, liver transplantation, treatment, sustained virological response. An emphasis was placed on randomised trials. Anti-viral therapy based on pegylated interferon and ribavirin must be considered before liver transplantation, but is poorly tolerated and has poor results in patients with cirrhosis and end-stage liver disease or hepatocellular carcinoma. Anti-viral therapy can be administrated systematically early after liver transplantation, or in patients with established recurrent chronic hepatitis. Combination of pegylated interferon alpha plus ribavirin results in a sustained virological response of up to 30% in patients with histological HCV recurrence. The results of a small trial of polyclonal anti-HCV to prevent recurrence were disappointing. Currently available anti-viral therapy is effective only in a minority of transplanted patients infected with HCV. Specifically targeted anti-viral therapies combining interferon alpha and ribavirin, or a combination of antiprotease and antipolymerase components, associated with a genetic prediction of anti-viral response and blocking HCV cell entry should improve the long-term prognosis of recurrent hepatitis C in the near future.


Optometry within hospitals at the Veterans Administration.
This study was designed to determine the use of optometrists with the Veterans Health Administration hospital system and to develop accurate statistics regarding the number and type of services these doctors provide. The findings help describe their responsibilities in the treatment and management of ocular diseases and their use of diagnostic and therapeutic drugs. The study also investigated what, if any, role optometrists play beyond care in the education and research practices of the hospital. A descriptive analysis was conducted through the use of surveys and interviews of department chiefs or medical directors. A survey was sent out to 149 Veterans Affairs (VA) Hospitals, located using the VA facility locator Web site. Data were tabulated, aggregated, and analyzed. A response rate of 81% was achieved (122 surveys returned), 98% of which (120 facilities) provide eye services to their patients in either an outpatient or inpatient capacity. One hundred seventeen (98%) of these had optometrists affiliated with their facility. These optometrists were responsible for providing a range of services, prescribing the use of diagnostic or therapeutic drugs, and participating in educational training of other health personnel. Optometry has developed a strong partnership with the Veterans Health Administration, and act as an integral part of its hospital services. The VA has developed a workforce mix that should serve as a model for managed care organizations.


Schistosomiasis control in the 21st century. Proceedings of the International Symposium on Schistosomiasis, Shanghai, July 4-6, 2001.
A total of 120 papers were presented at the International Symposium on Schistosomiasis which was held in Shanghai, July 4-6, 2001 with the theme of Schistosomiasis Control in the 21st Century. In order to focus more attention on the new challenges in control programmes for schistosomiasis as well as show the priority of research areas in new century, we summarize the advances of control programmes and researches in nine areas, including (1) Status of schistosomiasis control programmes; (2) Progress in applied field research; (3) Biology and control approaches of snail hosts; (4) Novel approaches for schistosomiasis control; (5) Pathogenesis and morbidity of the disease; (6) Immunology and vaccine development; (7) Screening of population for chemotherapy in low transmission areas; (8) Sustainable intervention methods in different endemic settings; (9) Impact of animal schistosomiasis on agricultural development and importance of its control; (10) GIS/RS application and environmental changes.


Biparietal osteodystrophy: Macroscopic appearance, computed tomography imaging and microarchitectural analysis.
Anatomical or morphological variations of the skull bones usually do not attract much attention among forensic pathologists. However, these variations can sometimes be an important marker in forensic identification of a person or represent a missing piece when solving a cranial trauma puzzle. In this article, we were interested in peculiar presentation of the thinning of both parietal bones (biparietal osteodystrophy). The course and etiology of this condition still remain unknown. In three autopsy cases with biparietal osteodystrophy (three females aged 95, 90 and 83) and no head trauma, we used conventional (CT) and microcomputed tomography (micro-CT) imaging of the skull and parietal bone specimens containing normal bone, transitional zone and thinned bone with osteodystrophy. CT images demonstrated an oval-shaped resorptive parietal bone depression with smooth contours, without marginal osteosclerotic changes or involvement of cranial sutures. In the transitional zone, micro-CT scans showed a decrease in total bone thickness and the thickness of diplöe, while inner and outer tables showed increased porosity. At the site of maximal thinness of the parietal bone, inner and outer tables fused and formed a thin layer of cortical bone. Skull thinning appeared due to the reduced thickness of diplöe, leading to egg-shell thinning in the central area of the parietal bones. A forensic pathologist should be familiar with this benign condition in order not to confuse it with resorptive bone diseases.


Antimicrobial resistance of pathogenic Aeromonas spp. isolated from marketed Pacific abalone (Haliotis discus hannai) in Korea.
The object of this study was to identify potential health concerns of the Aeromons spp. isolated from marketed Pacific abalone (Haliotis discus hannai) with respect to their virulence and antimicrobial resistance patterns. We identified 29 strains of aeromonads consisting of five species; Aeromonas hydrophila (n = 9), Aeromonas enteropelogenes (n = 14), Aeromonas veronii (n = 3), Aeromonas salmonicida (n = 2) and Aeromonas sobria (n = 1), by employing series of biochemical tests and gene sequencing. In the phenotypic virulence assays, all isolates showed gelatinase and caseinase activities, while lipase formation (69%), phospholipase production (90%), DNase formation (82%), slime production (49%) and haemolysis activity (α = 18% and β = 82%) were also detected among isolates. Prevalence of virulence genes; aerA (100%), fla (66%), ahyB (73%), act (52%), alt (42%), ast (35%), ser (52%), gcat (69%), ascV (43%), hlyA (83%), lip (52%) and exu (59%) were detected by PCR assays. In disc diffusion test, 100% resistance was detected against ampicillin while cephalothin, rifampicin, oxytetracycline, colistine sulphate, nalidixic acid and piperaciliin were resisted by 86, 73, 42, 35, 28, 20 and 20% of the isolates respectively. Thirteen (45%) of the isolates showed multiple antimicrobial resistance (MAR) indices ≥ 0·2. Our findings suggest that the potential health risk posed by the abalone-borne Aeromonas spp. should not be underestimated. This is the first time to evaluate possible public health risks upon consumption of abalone harbored Aeromonas spp. and also to isolate potential pathogenic and multidrug-resistant Aeromonas spp. from Pacific abalone in Korea.


Case report: unusually high rates of aneuploid embryos in a 28-year old woman with incontinentia pigmenti.
A young female carrier for incontinentia pigmenti underwent preimplantation genetic diagnosis to prevent the transfer of affected embryos. FISH diagnosis was performed using X, Y, 18 and 13/21 probes. Unexpectedly, 57% of the embryos were aneuploid for these chromosomes, a rate significantly higher (P < 0.005) than expected (9.3%). The patient achieved pregnancy but spontaneously aborted a trisomy 9 fetus.


Biomimetic actuators: where technology and cell biology merge.
The structural and functional analysis of biological macromolecules has reached a level of resolution that allows mechanistic interpretations of molecular action, giving rise to the view of enzymes as molecular machines. This machine analogy is not merely metaphorical, as bio-analogous molecular machines actually are being used as motors in the fields of nanotechnology and robotics. As the borderline between molecular cell biology and technology blurs, developments in the engineering and material sciences become increasingly instructive sources of models and concepts for biologists. In this review, we provide a--necessarily selective--summary of recent progress in the usage of biological and biomimetic materials as actuators in artificial environments, focussing on motors built from DNA, classical cellular motor systems (tubulin/kinesin, actin/myosin), the rotary motor F1F0-ATPase and protein-based 'smart' materials.


Acetylation-induced alteration of catalytic and regulatory properties of aspartase.
Acetylation of Escherichia coli aspartase (L-aspartate ammonia-lyase, EC 18.104.22.168) with acetic anhydride or N-hydroxysuccinimide acetate resulted in the alteration of catalytic and regulatory properties as follows. At pH 7.0, 2-fold activation was observed in 30 min, whereas at pH 8.5 the activity of the acetylated enzyme was lower than that of the native enzyme throughout the range of substrate concentrations tested, while maintaining the Vmax unchanged. The Hill coefficient values of the substrate saturation curves were also altered under both pH conditions to an appreciable extent toward higher values. The enzyme activity's requirement for divalent metal ions increased at both pH 7.0 and 8.5. In particular the ratio of the activities in the presence vs. absence of Mg2+ reached as high as 84.5 at the latter pH. Inspection of the acetylation-induced conformational change by difference absorption spectroscopy revealed that a red shift occurred in the ultraviolet region. Chemical analyses, including high-performance liquid chromatography, of the acetylated residues revealed that approximately three amino groups per subunit were acetylated concomitant with a 2.1-fold activation and that the acetylation site was restricted to a relatively specific region of the enzyme molecule. Acylation of the enzyme with other acid anhydrides such as n-butyric and propionic anhydrides also increased the activity at pH 7.0, although to a lesser extent.


Herpes simplex virus 1 evades cellular antiviral response by inducing microRNA-24, which attenuates STING synthesis.
STING is a nodal point for cellular innate immune response to microbial infections, autoimmunity and cancer; it triggers the synthesis of the antiviral proteins, type I interferons. Many DNA viruses, including Herpes Simplex Virus 1 (HSV1), trigger STING signaling causing inhibition of virus replication. Here, we report that HSV1 evades this antiviral immune response by inducing a cellular microRNA, miR-24, which binds to the 3' untranslated region of STING mRNA and inhibits its translation. Expression of the gene encoding miR-24 is induced by the transcription factor AP1 and activated by MAP kinases in HSV1-infected cells. Introduction of exogenous miR-24 or prior activation of MAPKs, causes further enhancement of HSV1 replication in STING-expressing cells. Conversely, transfection of antimiR-24 inhibits virus replication in those cells. HSV1 infection of mice causes neuropathy and death; using two routes of infection, we demonstrated that intracranial injection of antimiR-24 alleviates both morbidity and mortality of the infected mice. Our studies reveal a new immune evasion strategy adopted by HSV1 through the regulation of STING and demonstrates that it can be exploited to enhance STING's antiviral action.


Transcription inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) causes DNA damage and triggers homologous recombination repair in mammalian cells.
Transcription, replication and homologous recombination are intrinsically connected and it is well established that an increase of transcription is associated with an increase in homologous recombination. Here, we have studied how homologous recombination is affected during transcription inhibition by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), a compound that prevents activating phosphorylations of the RNA Pol II C-terminal domain. We identify that DRB triggers an increase in homologous recombination within the hprt gene as well as increasing RAD51 foci formation in mammalian cells. Furthermore, we find that DRB-induced transcriptional stress is associated with formation of the nuclear foci of the phosphorylated form of H2AX (γH2AX). We accounted that about 72% of RAD51 foci co-localized with the observed γH2AX foci. Interestingly, we find that XRCC3 mutated, homologous recombination defective cells are hypersensitive to the toxic effect of DRB and fail to form RAD51 foci. In conclusion, we show that DRB-induced transcription inhibition is associated with the formation of a lesion that triggers RAD51-dependent homologous recombination repair, required for survival under transcriptional stress.


Circulating microRNAs as Novel Biomarkers for Atherosclerosis.
In this study, we determined the expression of selected circulating microRNAs (miRNA) and their potential roles as biomarkers in patients with atherosclerosis and a control group. In order to obtain insight into miRNA expression levels in atherosclerosis, we analyzed miRNA expression levels by real-time polymerase chain reaction (RT-PCR) in case (n=89) and healthy control (n=93) groups. Receiver operating characteristic curve analysis was performed to assess the diagnostic capability of miRNAs. miRNA221 and miRNA221 expression levels were significantly lower in patients than controls (p=0.011 and p=0.004, respectively). Receiver operator curve analysis demonstrated that expression levels of miRNA221 [area under curve (AUC)=0.623, p=0.0086) and miRNA222 (AUC=0.654, p=0.0006) were significantly different between groups. There were positive correlations between miRNA122a and triglyceride (p=0.046) and very-low-density lipoprotein (p=0.029) levels. miRNA221 and miRNA222 could be convenient biomarkers for diagnosis of atherosclerosis.


CircRNA-100284 activates aurora kinase B by inducing methylation of HSP70 via microRNA-217 to promote proliferation of bladder cancer cells.
The malignant transformation of normal bladder cells (SV-HUC-1) was induced by arsenite to explore the possible mechanism of circRNA-100284 influencing bladder cancer cell proliferation. Normal bladder SV-HUC-1 cells were cultured with 2 μM arsenite to induce malignant transformation. After 0, 3, 6, 12, and 24 h of culture, the expression level of circRNA-100284 in cells was detected by quantitative real-time PCR. Western blotting assays were used to detect the expression levels of EZH2 and cyclin-D1 proteins in cells treated with different media. Cell cycle was analyzed by flow cytometry. In addition, through cell transfection and CCK-8 experiments, the effect and mechanism of circRNA-100284 targeting microRNA-217 on proliferation was determined. The interaction between HSP70 methylation and Aurora-B was determined by Western blotting and immunoprecipitation experiments. With prolonged contact time with arsenite, the expression level of circRNA-100284 in cells increased continuously (P < 0.05). Western blotting assays showed that the expression levels of EZH2 and cyclin-D1 proteins in arsenite-transformed cells increased. Flow cytometry and CCK-8 showed that circRNA-100284 accelerated cell cycle transition and cell proliferation through miR-217. Finally, after culturing human bladder cancer T24 cells, combined with immunoprecipitation and in vitro kinase experiments, it was found that K561- dimethyl HSP70 activated Aurora-B, thus promoting the proliferation of bladder cancer cells. CircRNA-100284 activates aurora kinase B by inducing methylation of HSP70 via microRNA-217 to promote the proliferation of bladder cancer cells.


[123I]iodoamphetamine SPECT imaging.
SPECT imaging of [123I]IMP is reviewed. Methods for radiopharmaceutical production are discussed with an emphasis on labeling small quantities of IMP. Limited angle tomography and full angle SPECT with standard cameras and special imaging systems are reviewed. Selection of collimator and methods of reconstruction are discussed. Clinical studies are described with emphasis on stroke, epilepsy and dementia. The efforts to perform quantitative imaging of rCBF with [123I]IMP are reviewed.


Selective histochemical localization of polysaccharides in tissue sections oxidized by acetic anhydride in dimethyl sulfoxide.
Oxidation of tissue sections by 25-30% (v/v) acetic anhydride (AA) in dimethyl sulfoxide (DMSO) resulted in facile induction of tissue carbonyls readily localized with Schiff's reagent and o-dianisidine but not with the 3-hydroxy-2-naphthoic acid hydrazide-tetraazotized diorthoanisidine method. Carbonyls generated by AA-DMSO oxidation were confined predomintly to substrates containing pyranosides. Oxidized furanosides, as represented by deoxyribonucleic acid and ribonucleic acid, gave only a residual color reaction. The AA-DMSO method possesses an advantage in that the oxidation of tissue polysaccharides does not proceed beyond the formation of carbonyly and is particularly suited for use after formol fixation.


High risk for sudden death identified by electrocardiographic loop recording in a patient with hypertrophic cardiomyopathy without major risk factors.
Recurrent presyncope is occasionally reported by patients with hypertrophic cardiomyopathy (HC). However, it is difficult to identify on 24-hour Holter recordings the mechanisms responsible for these infrequent symptoms. We report the case of a patient with HC with recurrent presyncope and without major sudden death risk factors, in whom electrocardiographic loop recording identified life-threatening arrhythmias as the mechanism responsible for these symptoms. Documentation of these arrhythmias justified implantation of a cardioverter-defibrillator in the absence of other risk factors.


Generation of IBMS-iPSC-015, -016, -017 human induced pluripotent stem cells (IBMSi013-A, IBMSi014-A, and IBMSi015-A) derived from patients with atrial fibrillation.
Atrial fibrillation is the most common heart disease in the world, with around 35 million patients in 2020. Here we reported the generation of IBMS-iPSC-015-06, IBMS-iPSC-016-06, and IBMS-iPSC-017-02 as human induced pluripotent stem cell (iPSC) lines from patients' peripheral blood mononuclear cells (PBMCs) with atrial fibrillation. The cell lines expressed properties of pluripotent stem cells, including pluripotent markers and the ability to differentiate into three germ layers. These cell lines served as suitable models for studying alternative therapies of atrial fibrillation.


Axotomy enhances the outgrowth of neurites from embryonic rat septal-basal forebrain neurons on a laminin substratum.
Previous studies have suggested that embryonic (nonaxotomized) and regenerating central nervous system neurons differentially respond to the same substrata. In the present study, we have used an in vitro model to test the ability of laminin and type I collagen to promote the outgrowth of neurites from nonaxotomized and axotomized, embryonic septal-basal forebrain (SBF) neurons. Neurons within explants derived from Embryonic Day (E) 15 rats extended neurites that demonstrated similar growth characteristics on a collagen or laminin substratum. E15 neurons could be induced to extend longer neurites on laminin if they were axotomized in vitro and subsequently replated onto a laminin substratum. The carbocyanine dye DiI indicated that neurons which were axotomized could survive and regenerate processes. These regenerating neurites grew 27% longer on laminin than they did on collagen. Similarly, neurons that were axotomized in situ, i.e., E18 SBF neurons, extended neurites that were 29% longer on a laminin substratum. In contrast, E15 explants that were maintained in suspension culture prior to being plated onto a substratum exhibited similar growth on laminin or collagen. The increase in regeneration by E15 neurons on laminin was augmented, by 22%, if nerve growth factor was supplemented to the culture medium. These results demonstrate that laminin is a better substratum, as compared to collagen, for the elongation of neurites from axotomized SBF neurons. Nonaxotomized neurites, on the other hand, do not appear to prefer one substratum over the other. Furthermore, regeneration from embryonic, SBF neurons on laminin is augmented if NGF is used simultaneously.


Acute Experimental Barrier Injury Triggers Ulcerative Colitis-Specific Innate Hyperresponsiveness and Ulcerative Colitis-Type Microbiome Changes in Humans.
The trigger hypothesis opens the possibility of anti-flare initiation therapies by stating that ulcerative colitis (UC) flares originate from inadequate responses to acute mucosal injuries. However, experimental evidence is restricted by a limited use of suitable human models. We thus aimed to investigate the acute mucosal barrier injury responses in humans with and without UC using an experimental injury model. A standardized mucosal break was inflicted in the sigmoid colon of 19 patients with UC in endoscopic and histological remission and 20 control subjects. Postinjury responses were assessed repeatedly by high-resolution imaging and sampling to perform Geboes scoring, RNA sequencing, and injury niche microbiota 16S ribosomal RNA gene sequencing. UC patients had more severe endoscopic postinjury inflammation than did control subjects (P < .01), an elevated modified Geboes score (P < .05), a rapid induction of innate response gene sets (P < .05) and antimicrobial peptides (P < .01), and engagement of neutrophils (P < .01). Innate lymphoid cell type 3 (ILC3) markers were increased preinjury (P < .01), and ILC3 activating cytokines were highly induced postinjury, resulting in an increase in ILC3-type cytokine interleukin-17A. Across groups, the postinjury mucosal microbiome had higher bacterial load (P < .0001) and lower α-diversity (P < .05). UC patients in remission respond to mucosal breaks by an innate hyperresponse engaging resident regulatory ILC3s and a subsequent adaptive activation. The postinjury inflammatory bowel disease-like microbiota diversity decrease is irrespective of diagnosis, suggesting that the dysbiosis is secondary to host injury responses. We provide a model for the study of flare initiation in the search for antitrigger-directed therapies.


Etiology and prevalence of ESBLs in adult community-onset urinary tract infections in East China: A prospective multicenter study.
Community onset urinary tract infections (COUTIs) drew attention recently owing to their increased prevalence and associations with resistant pathogens. The study is aimed at investigating the etiology of COUTIs as well as prevalence and the related risk factors of extended-spectrum β-lactamase (ESBL) in COUTIs in China. The prospective study was performed in nineteen hospitals during November 1, 2017 and August 31, 2019. Non-duplicated isolates from COUTIs were included. The ESBL phenotypic confirmation test was performed and whole genomes were sequenced for all the ESBL-positive bacteria for further analysis. The risk factors for ESBL-producing bacterial infections were analyzed using binary logistic regression. A total of 1760 COUTI cases were included in this study. Escherichia coli (1332, 75.7%), Klebsiella pneumoniae (110, 6.3%) and Enterococcus faecalis (52, 3.0%) were the top three common pathogens of COUTIs in China. The overall positive rate of ESBLs in Enterobacterales was 37.2% (562/1512). The age (OR=1.007, P = 0.041), solid malignant tumor (OR=1.668, P = 0.016), prostate diseases (OR=2.035, P = 0.010), history of lithotripsy for urinary calculi (OR=2.009, P = 0.030), history of urological surgery (OR=1.869, P = 0.009) and cephalosporin use within 3 months (OR=1.503, P = 0.025) were independent risk factors for ESBL-producing organisms causing COUTIs. The predominant ESBL types were CTX-Ms, among which CTX-M-14, CTX-M-55 and CTX-M-27 were the most common subtypes. ST131 and ST1193 were the predominant sequence types of ESBL-producing E. coli (ESBL-EC). Most of the tested antimicrobial agents showed significantly higher non-susceptible rates in the ESBL positive group as compared with ESBL-negative group (P < 0.05). Enterobacterales, especially E. coli, is the most common pathogen in COUTIs in China and ESBL-producers are highly prevalent. Thus, early prediction depending on risk factors seems to be crucial to determine the appropriate empirical therapy for infections caused by ESBL-producing pathogens.