Allocation of deceased donor kidneys in São Paulo, Brazil: effect of human leukocyte antigen compatibility on graft survival.
In Brazil, organ transplantation has been regulated by a federal law since 1997. This law was created to guarantee equal access to treatment on a national scale. Deceased donor organ procurement and sharing are centralized and controlled by the Health Department of each state of the nation, following a regional allocation policy. In São Paulo, time on the waiting list was the main criterion adopted to allocate deceased donor kidneys up to January 1, 2002. After that, HLA mismatches (MM) were the main criterion. The aim of this study was to investigate the impact of HLA compatibility on graft survival among 3312 consecutive kidney recipients. The 2-year kidney graft survival rates were compared among recipients transplanted based on the waiting time policy and based on HLA MM. Better results were observed in the HLA MM group (78.1% vs 64.9%; P < .0001). Regarding kidney allocation based on HLA MM, recipients transplanted with 0 HLA-A, -B, or -DR MM showed significantly better 5-year survival rates than those with 1-2 or 3-4 or 5-6 HLA-A, -B, or -DR MM (70.36% vs 64.71% vs 58.07% vs 55.64%; P < .050). We concluded that HLA compatibility is a feasible criterion to allocate deceased donor kidneys in Brazil.


The prevalence of and factors associated with antenatal depression among all pregnant women first attending antenatal care: a cross-sectional study in a comprehensive teaching hospital.
Antenatal depression has become a common and serious problem, significantly affecting maternal and fetal health. However, evaluation and intervention methods for pregnant women in obstetric clinics are inadequate. This study aimed to determine the prevalence of and risk factors for depression among all pregnant women at their first attending antenatal care in the obstetrics clinic, a comprehensive teaching hospital, southwest of China. From June to December 2019, 5780 pregnant women completed online psychological assessments, and data from 5728 of the women were analyzed. The women were categorized into two groups according to the presence or absence of depression. Depression was assessed by the Patient Health Questionnaire-9 (PHQ-9), with a cutoff point of 10 for depression. Anxiety and somatic symptoms were measured by the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-15 (PHQ-15), respectively. Univariate analysis and binary logistic regression analysis were used to determine the association among antenatal depression, anxiety, somatic symptoms and participants' characteristics. The prevalence of antenatal depression among all the pregnant women at their first attending antenatal care was 16.3%, higher in the first trimester (18.1%). Anxiety symptoms (Mild anxiety AOR = 2.937; 95% CI: 2.448-3.524) and somatic symptoms (Mild somatic symptoms AOR = 3.938; 95% CI: 2.888-3.368) were major risk factors for antenatal depression among women and the risk increased more with the anxiety level or somatic symptoms level. Gestational weeks (second trimester AOR = 0.611; 95% CI: 0.483-0.773; third trimester AOR = 0.337; 95% CI: 0.228-0.498) and urban residence (AOR = 0.786; 95% CI: 0.652-0.947) were protective factors for antenatal depression among women. About one in six pregnant women would experience depression, and special attention should be paid to some risk factors (i.e., early pregnancy, anxiety symptoms, somatic symptoms, rural residence). Online psychological assessments might be a time-saving and convenient screening method for pregnant women in obstetric clinics.


The impact of implementing a rapid response system: a comparison of cardiopulmonary arrests and mortality among four teaching hospitals in Australia.
To compare clinical outcomes between a teaching hospital with a mature rapid response system (RRS), with three similar teaching hospitals without a RRS in Sydney, Australia. For the period 2002-2009, we compared a teaching hospital with a mature RRS, with three similar teaching hospitals without a RRS. Two non-RRS hospitals began implementing the system in 2009 and a third in January 2010. We compared the rates of in-hospital cardiopulmonary arrest (IHCA), IHCA-related mortality, overall hospital mortality and 1-year post discharge mortality after IHCA between the RRS hospital and the non-RRS hospitals based on three separate analyses: (1) pooled analysis during 2002-2008; (2) before-after difference between 2008 and 2009; (3) after implementation in 2009. During the 2002-2008 period, the mature RRS hospital had a greater than 50% lower IHCA rate, a 40% lower IHCA-related mortality, and 6% lower overall hospital mortality. Compared to 2008, in their first year of RRS (2009) two hospitals achieved a 22% reduction in IHCA rate, a 22% reduction in IHCA-related mortality and an 11% reduction in overall hospital mortality. During the same time, the mature RRS hospital showed no significant change in those outcomes but, in 2009, it still achieved a crude 20% lower IHCA rate, and a 14% lower overall hospital mortality rate. There was no significant difference in 1-year post-discharge mortality for survivors of IHCA over the study period. Implementation of a RRS was associated with a significant reduction in IHCA, IHCA-related mortality and overall hospital mortality.


A nested case-control study of leukemia mortality and ionizing radiation at the Portsmouth Naval Shipyard.
A nested case-control study using conditional logistic regression was conducted to evaluate the exposure-response relationship between external ionizing radiation exposure and leukemia mortality among civilian workers at the Portsmouth Naval Shipyard (PNS), Kittery, Maine. The PNS civilian workers received occupational radiation exposure while performing construction, overhaul, repair and refueling activities on nuclear-powered submarines. The study age-matched 115 leukemia deaths with 460 controls selected from a cohort of 37,853 civilian workers employed at PNS between 1952 and 1992. In addition to radiation doses received in the workplace, a secondary analysis incorporating doses from work-related medical X rays and other occupational radiation exposures was conducted. A significant positive association was found between leukemia mortality and external radiation exposure, adjusting for gender, radiation worker status, and solvent exposure duration (OR = 1.08 at 10 mSv of exposure; 95% CI = 1.01, 1.16). Solvent exposure (including benzene and carbon tetrachloride) was also significantly associated with leukemia mortality adjusting for radiation dose, radiation worker status, and gender. Incorporating doses from work-related medical X rays did not change the estimated leukemia risk per unit of dose.


Can Published Population Pharmacokinetic Models of Busulfan Be Used for Individualized Dosing in Chinese Pediatric Patients Undergoing Hematopoietic Stem Cell Transplantation? An External Evaluation.
Busulfan is a bifunctional alkylating agent that is widely used before hematopoietic stem cell transplantation (HSCT), in combination with other chemotherapeutic drugs. As of 2020, there is no population pharmacokinetic (popPK) model for busulfan in Chinese pediatric patients. A systemic external evaluation of 11 published popPK models was conducted in Chinese pediatric patients undergoing HSCT. Forty pediatric patients were enrolled in this study, with a total of 183 blood concentrations. The relative prediction error (PE%), median PE%, median absolute PE%, and percentage of PE% within ±20% and ±30% were calculated in prediction-based diagnostics. Simulation-based diagnostics were conducted through a prediction- and variability-corrected visual predictive check and the normalized prediction distribution error. The relative individual prediction error was calculated using Bayesian forecasting with 1 to 3 concentration points. The 1-compartment open linear popPK model, which was built by Su-jin Rhee et al (model H), incorporating the patient's body surface area, age, dosing day, and aspartate aminotransferase as significant covariates had preferable predictability than other popPK models. In prediction-based diagnostics, the median PE%, percentage of PE% within ±20%, and percentage of PE% within ±30% of model H were 8.48%, 45.35%, and 59.56%, respectively. The normalized prediction distribution error of model H showed that it followed the normal distribution. Based on Bayesian forecasting, model H showed good predictive performance. Thus, model H was the most appropriate model that can be used clinically for individualized dosage adjustments in Chinese pediatric HSCT patients.


Ruthenium-catalyzed ring-closing metathesis accelerated by long-range steric effect.
Ruthenium-based metathesis catalysts with a N-heterocyclic carbene ligand bearing 2,3,4,5-tetraphenylphenyl moieties (1-TPPh and 1-TPPh*) are developed. The highly active catalyst system has been realized in THF by the combination of 1-TPPh* and CuCl as a phosphine scavenger.


Effects of polycyclic aromatic hydrocarbons on biomarker responses in Gambusia yucatana, an endemic fish from Yucatán Peninsula, Mexico.
Polycyclic aromatic hydrocarbons (PAHs) are petroleum components that, when dissolved in the aquatic environment, can disrupt normal animal physiological functions and negatively affect species populations. Gambusia yucatana is an endemic fish of the Yucatán Peninsula that seems to be particularly sensitive to the presence of PAHs dissolved in the water. Here, we examined PAH effects on gene expressions linked to endocrine disruption and biotransformation in this species. Specifically, we examined the expression of vitellogenin I (vtg1), vitellogenin II (vtg2), oestrogen receptor α (esr1), oestrogen receptor β (esr2), aryl hydrocarbon receptor (AhR) and the cytochrome P4503A (CYP3A) genes. We exposed G. yucatana to different concentrations of PAHs (3.89, 9.27, 19.51 μg/L) over a period of 72 h and found changes associated with reproduction, such as increases in hepatic expression of vtg, esr, AhR and CYP3A, mainly at concentrations of 9.27 and 19.51 μg/L. Our results also indicate that benzo[a]pyrene was probably the main PAH responsible for the observed effects. The genes examined here can be used as molecular markers of endocrine-disrupting compounds, as the PAHs, present in the environment, as gene expression increases could be observed as early as after 24 h. These biomarkers can help researchers and conservationists rapidly identify the impacts of oil spills and improve mitigation before the detrimental effects of environmental stressors become irreversible.


Presence of circulating endothelial progenitor cells and levels of stromal-derived factor-1α are associated with ascending aorta aneurysm size.
Circulating endothelial progenitor cells (EPCs) are a specialized subset of stem/progenitor cells found in bone marrow. They participate in neo-vascularization of injured vessels and predict cardiovascular outcome in patient at risk. Several factors influence their migration and proliferation, among which is the widely studied stromal-derived factor-1α (SDF-1α). In cardiovascular disease, regarding thoracic aortic aneurysms (TAAs), few studies have investigated the levels of EPC and SDF-1α. As rupture, acute dissection and hematoma are acute complications of idiopathic ascending thoracic aortic aneurysm (iATAA) that increase with the size of aneurysm, we aimed to evaluate a potential relationship between circulating EPC and SDF-1α and iATAA size. The aneurysm size of 27 consecutive patients suffering from iATAA and scheduled for surgery was assessed by computed tomography scan. In all patients, we measured levels of circulating EPCs by flow cytometer, and plasma levels of SDF-1α the day before surgery. The median aneurysm size was 54 mm (interquartile range (IQR): 50.0-58.8]. The EPC levels of CD34+/CD144+/CD14- and CD34+/VEGF-R2+/CD14- were inversely correlated to aneurysm diameter (p = 0.038, r = -0.424 and p = 0.0046, r = -0.65, respectively) before surgery. Conversely, plasma levels of SDF-1α were positively correlated to aneurysm size (p = 0.042; r = 0.47). Our findings indicate that EPC levels may be useful for monitoring ascending aorta aneurysms and that SDF-1α could be a biomarker of iATAA expansion.


Liprin-α is involved in exocytosis and cell spreading in mast cells.
The active zone is a specialized region of the presynaptic plasma membrane where the neurotransmitter release occurs by exocytosis. Mast cells also release inflammatory mediators by exocytosis resulting in induction of allergic responses. In our previous reports, we found that active zone proteins, Munc13-1 and ELKS regulates exocytosis of mast cell positively. In this study, we investigated the involvement of liprin-α, another active zone protein, in exocytosis in mast cells. We found that three isoforms of liprin-α, liprin-α1, -α2 and -α3 were expressed. Immunocytochemical experiments revealed that liprin-α1 resided both in the cytoplasm and on the plasma membrane. Upon stimulation with antigen, the area of a cell increased remarkably due to cell spreading and the distribution of liprin-α1 became punctuated. Interestingly, knockdown of liprin-α1 caused decrease in exocytotic release and cell spreading. These results suggest that liprin-α1 facilitates exocytosis and cell spreading, and these events might have correlated each other in mast cells.


[Nephrotic syndrome in scleroderma].
The renal affectation is infrequent in scleroderma, unlike other collagen diseases. The appearance of nephrotic syndrome has been related to the drug use, specially the D-penicilamine, or rarely as a manifestation of secondary amilodosis, quite infrequent in scleroderma. We report a case of nephrotic syndrome in a patient with systemic scleroderma, produced by a membranous glomerulonephritis, exceptionally described in literature.


Immune checkpoint inhibitors in GBM.
The purpose of this review is to summarize recent updates regarding immune checkpoint inhibitor therapy in GBM patients including updates in brain immunology, clinical trials, mechanisms of resistance, and biomarkers of response. PubMed was searched to identify recent relevant articles on immune checkpoint inhibitor therapy as it pertains to GBM. Clinicaltrials.gov was also searched to identify relevant clinical trials. The reported randomized phase 2 and 3 clinical trials of immune checkpoint inhibitors (alone or in combination with standard therapy) have not demonstrated a survival benefit to date in either newly diagnosed or recurrent GBM. A small randomized surgical study of neoadjuvant and adjuvant pembrolizumab suggested an increase in PFS and OS compared to adjuvant pembrolizumab only; further studies are needed to validate this finding. Despite the positive impact of immune checkpoint inhibitors in many cancers, only a small subset of GBM patients respond to these agents. Further research is needed to identify biomarkers of response and therapies to rationally combine with immune checkpoint inhibitors.


Intercellular adhesion molecule-1 gene polymorphism in Iranian patients with multiple sclerosis.
Intercellular adhesion molecule-1 (ICAM-1), an important molecule in leucocyte activation and migration, is expressed on the CNS endothelial cells of patients with multiple sclerosis. This study was conducted to determine whether ICAM-1 gene polymorphism influences the risk of developing multiple sclerosis in an Iranian population. We studied 157 patients with definite multiple sclerosis and 156 ethnically matched controls. The patients and the controls were genotyped for ICAM-1 gene polymorphism at codons 241 (exon 4) and 469 (exon 6). G/R241 and K/E 469 allele and genotype distribution did not show any significant difference between patient and control groups. We concluded that role of the ICAM-1 gene polymorphisms in the pathogenesis of multiple sclerosis is still controversial and should be studied further.


re- and si-Face-Selective Nitroaldol Reactions Catalyzed by a Rigid Chiral Quaternary Ammonium Salt: A Highly Stereoselective Synthesis of the HIV Protease Inhibitor Amprenavir (Vertex 478).
Either amprenavir (1) or its C(2) diastereomer can be synthesized in a simple way by the use of a nitroaldol reaction carried out in the presence of one or the other of the two ammonium ions 2. The 1,3-diamino-2-hydroxypropyl structural element of 1 is also found in many other peptidomimetics and HIV protease inhibitors. Described here is a new strategy for possible application to direct and stereocontrolled synthesis of such compounds.


Prognostic factors in the management of pediatric subglottic stenosis.
We report outcomes of endoscopic interventions in the management of pediatric subglottic stenosis (SGS), and factors that lead to open airway reconstruction. A retrospective cohort review of all pediatric patients with SGS, treated by a single surgeon, at a tertiary academic medical center from 2012 to 2020 was conducted. Variables recorded included patient demographics, initial grade of stenosis, gestational age, length of intubation, comorbidities as well as total number of interventions. A total of 47 patients were included in the study, of which 51% (n = 24) were female. Laryngotracheal reconstruction (LTR) was performed in 49% (n = 23) of patients. Decannulation was achieved in 25 of 32 tracheostomized patients. Fifteen patients did not have tracheostomy. There was a significant difference in gestational age (28.7 ± 5.36 vs 33.2 ± 6.13), initial grade of stenosis (2.3 ± 0.82 vs 1.6 ± 0.88), and total number of interventions (5.7 ± 2.8 vs 2.3 ± 1.5) when stratifying patients proceeding to LTR versus not (p < 0.05). There was no significant difference, however, in the length of intubation between the two groups. Of the comorbidities recorded, none were found to have a significant impact on the outcome. Subglottic stenosis is a challenging condition to treat, often requiring multiple interventions including LTR. We propose a set of risk factors that may assist in the treatment of SGS patients with certain comorbidities to minimize interventions and maximize outcomes.


Performance of Afirma Gene Sequencing Classifier versus Gene Expression Classifier in thyroid nodules with indeterminate cytology.
About 15% to 30% of thyroid fine-needle aspiration (FNA) nodules have indeterminate cytology. The Afirma (Veracyte Inc, South San Francisco, CA) Gene Expression Classifier (GEC)/Gene Sequencing Classifier (GSC) tests were designed to improve risk stratification of the indeterminate thyroid nodules. This study aimed to evaluate and compare the performance of the Afirma GEC and GSC tests in the indeterminate thyroid lesions. Thyroid FNA cases with indeterminate cytology were searched in the pathology database and only those with available Afirma results were selected for this study. Each patient's demographic, sonographic, cytologic, molecular, and subsequent surgical follow-up results were collected and analyzed. There were 100 cases with indeterminate thyroid FNA results, including 49 cases tested by GEC and 51 cases by GSC. In the GEC group, benign call rate (BCR) was 53% (26 of 49) and the calculated negative predictive value (NPV) and positive predictive value (PPV) were 88% and 47% respectively. In the GSC group, the BCR was 63% (32 of 51) and the calculated NPV and PPV were 100% and 64%, respectively. Whereas only 17% (1 of 6) of benign oncocytic lesions were tested benign by the GEC, 60% (3 of 5) of benign oncocytic nodules were tested benign by the GSC. We demonstrated in this study that a little more than half of the indeterminate thyroid nodules had negative Afirma GEC/GSC results and the BCR using the Afirma GSC test was higher than GEC. The Afirma GSC showed higher NPV and PPV than GEC. In addition, the Afirma GSC appeared to be superior for differentiating benign and malignant oncocytic thyroid lesions.


ProteinChip technology is a useful method in the pathogenesis and diagnosis of endometriosis: a preliminary study.
To test the feasibility of ProteinChip (Ciphergen Biosystems, Inc., Fremont, CA) technology as a proteomic tool in discovering and identifying proteins that are differentially expressed in endometrium, endometriotic tissue, and normal peritoneum from women with and without endometriosis. Differential analysis of protein expression in women with and without endometriosis. University hospital. A total of nine patients during their secretory phase (days 20-22) were selected for this study on the basis of cycle phase and presence/or absence of endometriosis. Twelve tissues used in the study included six endometrial biopsies from women with mild endometriosis (n = 3) and a normal pelvis (n = 3) as well as paired samples of peritoneal endometriotic lesions (n = 3) and macroscopically normal peritoneum biopsies (n = 3) from three women with endometriosis. Numerous expression differences were observed in the above comparisons, representing both up-regulation and down-regulation in protein and peptide expression levels. Endometrial expression for a number of proteins and peptides in the range of 2.8-12.3 kDa was 3-24 times lower in women with endometriosis than in those without endometriosis. When compared with normal peritoneum, endometriotic lesions showed an increased expression for a set of proteins and peptides in the range of 3-96 kDa, and especially an up-regulated cluster of proteins between 22 and 23 kDa, identified to be transgelin, a smooth muscle actin-binding protein. This preliminary study demonstrated that differential protein profiling by using ProteinChip array technology is feasible, reproducible, and may be developed into a powerful tool for endometriosis research.


Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review.
The authors present the clinical case of a 67-year-old man with severe insomnia for 5 years with an exacerbation about 1 year before consultation. He did not have enough concentration and energy for his daily work and developed depression and anxiety because of his excessive daytime sleepiness. During his insomniac state, a drug treatment provided partial relief, but the effects were not long-lasting. Consequently, the drug dosage increased, and major side effects gradually manifested. We decided to use a completely new therapeutic strategy for this patient to improve his sleep quality and mental symptoms. In time, the patient could stop oral medications and that is multimodal sleep. After the end of multimodal sleep, the patient typically experiences improvement in sleep quality and architecture. Additionally, the dosage of hypnotics used before multimodal sleep is discontinued without severe withdrawal symptoms. Zhang J-F, Williams JP, Zhao Q-N, et al. Multimodal sleep, an innovation for treating chronic insomnia: case report and literature review. J Clin Sleep Med. 2021;17(8):1737-1742.


RNA Sequencing Best Practices: Experimental Protocol and Data Analysis.
The genome-wide analysis of gene transcription using RNA sequencing (RNA-seq) has become the method of choice for characterizing and understanding transcriptional regulation in yeasts. RNA-seq has largely supplanted microarray based approaches in recent years due to improved accuracy and flexibility in the high-throughput identification and quantification of transcripts. The improvements associated with a sequencing approach compared to one based on hybridization, however, are accompanied by new experimental considerations related to both the collection and the analysis of the transcriptome data. Consensus approaches for processing and analysing the RNA-seq data in particular have yet to be arrived at, and it is possible to feel overwhelmed when surveying all the software tools that have been developed and recommended for these tasks. This chapter considers these issues in the context of providing general guidelines to help achieve best practice in yeast RNA-seq studies, and recommends a small number of the best performing tools that are currently available.


Further studies of the aggressive behavior induced by delta9-tetrahydrocannabinol in REM sleep-deprived rats.
The aggressive behavior induced by delta9-tetrahydrocannabinol in pairs of REM sleep-deprived rats was studied in five experiments by measuring dominant and submissive behavioral patterns. When 2 REM-deprived rats received delta9-THC, one of the animals displayed very aggressive postures, while its partner assumed incomplete defensive postures. The intensity of these behavioral postures was dose-dependent. In pairs composed of one REM-deprived rat injected with delta9-THC and one normal or one REM-deprived partner injected with control solution the deprived/drugged rat showed an aggressive posture and catatonia, or a strikingly bizarre behavior, while the control partner displayed typical defensive postures. The behavioral alterations induced in REM-deprived rats by amphetamine, LSD-25, and pentobarbital failed to provoke defense postures in the normal rats paired with them; however, apomorphine partially mimicked the delta9-THC-effects. It is concluded that in REM-deprived rats delta9-THC not only provokes aggressive behavior but also impairs the defensive-submissive behavioral patterns.


Influence of Cys-130 S. aureus alpha-toxin on planar lipid bilayer and erythrocyte membranes.
Replacement of an amino acid residue at position 130 -Gly by Cys- in the primary structure of Staphylococcus aureus alpha-toxin decreases the single-channel conductance induced by the toxin in planar lipid bilayers. Concomitantly, the pH value at which the channel becomes unable to discriminate between Cl- and K+ ions is also decreased. By contrast, the pH dependence of the efficiency of the mutant toxin to form ion channels in lipid bilayers was unchanged (maximum efficiency at pH 5.5-6.0). The asymmetry and nonlinearity of the current-voltage characteristics of the channel were increased by the point mutation but the diameter of the water pore induced by the mutant toxin, evaluated in lipid bilayers and in erythrocyte membranes, was found to be indistinguishable from that formed by wild-type toxin and equal to 2.4-2.6 nm. Alterations at the "trans mouth" were found to be responsible for all observed changes of the channel properties. This mouth is situated close to the surface of the second leaflet of a bilayer lipid membrane. The data obtained allows us to propose that the region around residue 130 in fact determines the main features of the ST-channel and takes part in the formation of the trans entrance of the channel.


Axon arbors and synaptic connections of a vulnerable population of interneurons in the dentate gyrus in vivo.
The predominant gamma-aminobutyric acid (GABA)ergic neuron class in the hilus of the dentate gyrus consists of spiny somatostatinergic interneurons. We examined the axon projections and synaptic connections made by spiny hilar interneurons labeled with biocytin in gerbils in vivo. Axon length was 152-497 mm/neuron. Sixty to 85% of the axon concentrated in the outer two thirds of the molecular layer of the dentate gyrus. The septotemporal span of the axon arbor extended over 48-82% of the total hippocampal length, which far exceeds the septotemporal span of axons of granule cells whose complete axon arbors extended over 15-29%. A three-dimensionally reconstructed 216-microm-long spiny hilar interneuron axon segment in the outer third of the molecular layer formed an average of 1 synapse every 5.1 microm. Of the 42 symmetric (inhibitory) synapses formed by the reconstructed segment, 88% were with spiny dendrites of presumed granule cells, and 67% were with dendritic spines that also receive an asymmetric (excitatory) contact from an unlabeled axon terminal. Postembedding GABA-immunocytochemistry revealed that 55% of the GABAergic synapses in the outer third of the molecular layer were with spines. Therefore, in the outer molecular layer, spiny hilar interneurons form synaptic contacts that appear to be positioned to exert inhibitory control near sites of excitatory synaptic input from the entorhinal cortex to granule cell dendritic spines. These findings demonstrate far-reaching, yet highly specific, connectivity of individual interneurons and suggest that the loss of spiny hilar interneurons, as occurs in temporal lobe epilepsy, may contribute to hyperexcitability in the hippocampus.


BatMeth: improved mapper for bisulfite sequencing reads on DNA methylation.
DNA methylation plays a crucial role in higher organisms. Coupling bisulfite treatment with next generation sequencing enables the interrogation of 5-methylcytosine sites in the genome. However, bisulfite conversion introduces mismatches between the reads and the reference genome, which makes mapping of Illumina and SOLiD reads slow and inaccurate. BatMeth is an algorithm that integrates novel Mismatch Counting, List Filtering, Mismatch Stage Filtering and Fast Mapping onto Two Indexes components to improve unique mapping rate, speed and precision. Experimental results show that BatMeth is faster and more accurate than existing tools. BatMeth is freely available at http://code.google.com/p/batmeth/.


Dysregulated circ_0004913, circ_0008160, circ_0000517, and their potential as biomarkers for disease monitoring and prognosis in hepatocellular carcinoma.
Circular RNA_0004913 (circ_0004913), circular RNA_0008160 (circ_0008160), and circular RNA_0000517 (circ_0000517) are shown to be dysregulated in HCC tissues and cell lines, and also show potential in regulating hepatocellular carcinoma (HCC) pathogenesis. This current study attempted to find possible associations of circ_0004913, circ_0008160, and circ_0000517 with clinical features and prognosis of HCC patients. A hundred and fifty HCC patients who received hepatectomy were retrospectively reviewed, and their resected specimens including tumor tissues and paired adjacent tissues were obtained, in which the circ_0004913, circ_0008160, and circ_0000517 expressions were detected. Overall survival (OS) data were collected according to the clinical visit records. Circ_0004913 (p < 0.001) and circ_0008160 (p < 0.001) were downregulated, while circ_0000517 (p < 0.001) was upregulated in tumor tissue compared with paired adjacent tissue. Additionally, tumor circ_0004913 was negatively associated with largest tumor size (p = 0.009) and Barcelona clinic liver cancer (BCLC) stage (p = 0.020), while tumor circ_0008160 and circ_0000517 were not correlated with any clinicopathological features of HCC patients (all p > 0.05). Tumor circ_0004913 high expression was associated with prolonged OS in total HCC patients (p = 0.008) and in subgroup of patients with largest tumor size <5 cm (p = 0.008). Tumor circ_0008160 high expression was correlated with longer OS in patients with BCLC stage B (p = 0.026). Univariate Cox's analysis disclosed that tumor circ_0004913 high expression was correlated with longer OS; while after adjustment by multivariate Cox's analysis, it failed to predict OS independently. Circ_0004913 was downregulated in tumor tissue and may serve as a biomarker for evaluating disease severity and prognosis in HCC patients.


A cohort study of dietary fibre intake and menarche.
To evaluate the influence of dietary fibre on menarche in a cohort of pre-menarcheal girls. Prospective cohort study. Ontario, Canada. Free-living pre-menarcheal girls (n = 637), 6 to 14 years of age. Information on dietary intake, physical activity and date of menarche was collected at baseline and was updated annually by self-administered questionnaires for three years. Cox proportional hazards models were used to evaluate the association between dietary fibre and menarche, adjusting for age at entry to the study and potential confounders. A higher intake of energy-adjusted dietary fibre was associated with a lower risk of (i.e. a later age at) menarche (relative hazard 0.54, 95% confidence interval (CI) 0.31-0.94 for highest vs. lowest quartile, P for trend = 0.027). At the fibre component level, a higher intake of energy-adjusted cellulose was associated with a lower risk of menarche (relative hazard 0.45, 95% CI 0.26-0.76, P for trend = 0.009). The findings are consistent with the hypothesis that pre-menarcheal dietary intake can influence menarche.


Statistical age-period-cohort analysis: a review and critique.
Descriptive and statistical age-period-cohort (APC) analysis methods have received considerable attention in the literature. The statistical modeling of APC data often involves the popular multiple classification model, a model containing the effects of age groups (rows), periods of observation (columns), and birth cohorts (diagonals of the age-by-period table). The identifiability problem inherent to this model is discussed, and its adverse effects on the results of APC modeling exercises are illustrated numerically. Potential problems attendant with the use of two-factor models are described, and other possible modeling approaches currently in use are discussed. Interpretational limitations due to certain innate characteristics of typical APC data sets are also detailed. Given all the documented potential sources for error, the current state-of-the-art regarding the statistical modeling of APC data should be considered to be at an early stage of development.


Closure of the anterior and posterior fontanelle in the New Zealand population: A computed tomography study.
Significant ethnic variation has been demonstrated in the closure of the anterior fontanelle (AF); however, to date, this has not been investigated in the Māori/Pasifika population. The computed tomography scans of 163 individuals (116 Māori/Pasifika and 47 New Zealand (NZ) European) aged between birth and 4 years were retrospectively analysed to investigate the surface area (SA) and time of closure of the anterior and posterior fontanelles in New Zealand. The Māori/Pasifika group showed clinical AF closure (SA < 114 mm2 ) rates of 25% at 4-6 months, increasing to 47% at 10-12 months and 80% at 13-18 months. The posterior fontanelle was clinically unfused in 17% of the Māori/Pasifika group aged <1 month and in 7% of the 1-3-month-old group. No cases of posterior fontanelle non-fusion were identified in the NZ European population. This study establishes normal values for AF size and closure frequency for the first time in the paediatric Māori/Pasifika population.


Quantitative recovery of Burkholderia pseudomallei from soil in Thailand.
Melioidosis is common in north-eastern Thailand, but is reported rarely from the adjacent areas of central Thailand, although rice farming is common to both regions. Quantitative soil cultures for Burkholderia pseudomallei were therefore prepared on 12 rice farms in both regions. B. pseudomallei was isolated from a similar proportion of rice fields in the central region (6/12) and in the north-east (7/12). Within the culture-positive sites, the number of B. pseudomallei colony-forming units (cfu) per mL of soil/water supernatant was significantly higher in the north-east (median 230 cfu/mL; range 1-17,000) than in the central region (median 10 cfu/mL; range 1-600). As bacterial counts in the soil are probably related to the risk of developing melioidosis, differences in exposure to B. pseudomallei probably contribute to the considerable differences in the incidence of this disease between these 2 adjacent regions.


[Using systemic corticotherapy for adult gonococcal keratoconjunctivitis: three case reports].
adult gonococcal keratoconjunctivitis is a rare disease possibly leading to blindness, whose severity is related to the risk of corneal perforation and whose progression is conditioned by the rapidity of diagnosis and therapeutic management. discuss the value of general corticotherapy in the treatment of scleritis associated with this disease. retrospective analysis of patients with adult gonococcal keratoconjunctivitis managed in an emergency setting in 2007. three patients aged 22-55 years contracted the disease during unprotected sexual activity. Involvement was bilateral in two cases out of three; the intensity of the signs was always asymmetrical. Each patient underwent stromal melting of the superior limbic structures, with severity proportional to the delay in treatment. For each case, systemic and local antibiotics did not control corneal thinning, which seemed correlated with the intensity of the systematically associated signs of scleral inflammation. Treatment of scleritis with general corticotherapy under antibiotic cover stabilized the corneal thickness. whether the physiopathology of perilimbic corneal thinning can lead to ocular perforation in this condition is unknown. In our experience, the stabilization of corneal thickness seems correlated with regression of the scleritis observed after introducing general corticotherapy, potentially indicating aseptic inflammatory involvement. stromal melting of the limbus observed in adult gonococcal keratoconjunctivitis seems to be related to the associated scleritis. Systemic corticotherapy controls progression and reduces the risk of corneal perforation.


Helping smokers with depression to quit smoking: collaborative care with Quitline.
To report smokers' evaluations and uptake of Quitline-doctor comanagement of smoking cessation and depression, a key component of the Victorian Quitline's tailored call-back service for smokers with a history of depression and to explore its relationship to quitting success. Prospective study followed Quitline clients disclosing doctor-diagnosed depression (n = 227). Measures were taken at baseline (following initial Quitline call), posttreatment (2 months) and 6 months from recruitment (77% and 70% response rates, respectively). Uptake of comanagement (initiated by fax-referral to Quitline), making a quit attempt (quit for 24 hours), sustained cessation (> 4 months at 6-month follow-up). At 2-month follow-up, 83% thought it was a good idea to involve their doctor in their quit attempt, 74% had discussed quitting with their doctor, and 43% had received comanagement. In all, 72% made a quit attempt, 37% and 33% were abstinent posttreatment and at 6 months, respectively, and 20% achieved sustained cessation. Among participants who discussed quitting with their doctor, those receiving comanagement were more likely to make a quit attempt than those who did not receive comanagement (78% v 63%). Participants with comanagement also received more Quitline calls (mean 4.6 v 3.1) - a predictor of sustained cessation. Exacerbation of depression between baseline and 6 months was reported by 18% of participants but was not related to cessation outcome. Quitline-doctor comanagement of smoking cessation and depression is workable, is valued by smokers, and increases the probability of quit attempts. Smoking cessation did not increase the risk of exacerbation of depression.


The mechanisms underpinning anthocyanin accumulation in a red-skinned bud sport in pear (Pyrus ussuriensis).
In our study, we demonstrated that histone acetylation promotes anthocyanin accumulation in pears by affecting the expression of key genes. Color is an important trait of horticultural plants, and the anthocyanin content directly affects the nutritional value and commercial value of colored fruits. Therefore, it is important for fruit breeding to cultivate new varieties with bright colors. 'Nanhong' (NH) pear (Pyrus ussuriensis) is a bud sport cultivar of 'Nanguo' (NG) pear. The anthocyanin content in NH pear is significantly higher than that in NG pear, but the underlying molecular mechanism remains unclear. Here, we observed that the anthocyanin biosynthesis structural gene PuUFGT (UDP-glucose: flavonoids 3-O-glucosyltransferase) and an anthocyanin transporter gene PuGSTF6 (glutathione S-transferase) had significantly higher expression levels in NH than in NG pears during the late stages of fruit development. Meanwhile, the R2R3-MYB transcription factor PuMYB110a was also highly expressed in NH pears and could positively regulate the transcription of PuUFGT and PuGSTF6. Overexpression of PuMYB110a in pear increased the fruit anthocyanin content. In addition, despite no significant differences in methylation levels being found in the promoters of PuMYB110a, PuUFGT, and PuGSTF6 when comparing the two varieties, the histone acetylation levels of PuMYB110a were significantly higher in NH pear compared with those in NG pear. Our findings suggest a mechanism for anthocyanin accumulation in NH fruit.


Upstream signaling of protein kinase C-epsilon in xenon-induced pharmacological preconditioning. Implication of mitochondrial adenosine triphosphate dependent potassium channels and phosphatidylinositol-dependent kinase-1.
Xenon elicits preconditioning of the myocardium via protein kinase C-epsilon. We determined the implication of (1) the mitochondrial adenosinetriphosphate dependent potassium (K(ATP)) channels and (2) the 3'phosphatidylinositol-dependent kinase-1 (PDK-1) in activating protein kinase C-epsilon. For infarct size measurements, anaesthetized rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Rats received xenon 70% during three 5-min periods before ischaemia with or without the K(ATP) channel blocker 5-hydroxydecanoate or Wortmannin as PI3K/PDK-1 inhibitor. For Western blot, hearts were excised at five time points after xenon preconditioning (Control, 15, 25, 35, 45 min). Infarct size was reduced from 42+/-6% (mean+/-S.D.) to 27+/-8% after xenon preconditioning (P<0.05). Western blot revealed an increased activation of PKC-epsilon after 45 min and of PDK-1 after 25 min during xenon preconditioning. 5-hydroxydecanoate and Wortmannin blocked both effects. PKC-epsilon is activated downstream of mitochondrial K(ATP) channels and PDK-1. Both pathways are functionally involved in xenon preconditioning.


Automatic generation of gene finders for eukaryotic species.
The number of sequenced eukaryotic genomes is rapidly increasing. This means that over time it will be hard to keep supplying customised gene finders for each genome. This calls for procedures to automatically generate species-specific gene finders and to re-train them as the quantity and quality of reliable gene annotation grows. We present a procedure, Agene, that automatically generates a species-specific gene predictor from a set of reliable mRNA sequences and a genome. We apply a Hidden Markov model (HMM) that implements explicit length distribution modelling for all gene structure blocks using acyclic discrete phase type distributions. The state structure of the each HMM is generated dynamically from an array of sub-models to include only gene features represented in the training set. Acyclic discrete phase type distributions are well suited to model sequence length distributions. The performance of each individual gene predictor on each individual genome is comparable to the best of the manually optimised species-specific gene finders. It is shown that species-specific gene finders are superior to gene finders trained on other species.


Cytosol progesterone and 17 alpha-hydroxyprogesterone levels and luteinizing hormone and chorionic gonadotropin receptors in human corpora lutea.
Cytosol progesterone (P) and 17 alpha-hydroxyprogesterone (17-OHP) levels and luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptors were measured in 27 corpora lutea and four corpora albicantia. Cytosol P concentrations were highest in corpora lutea (mean +/- SEM, 3.1 +/- 0.8 micrograms/g) during the midluteal phase (days 15 to 19) rather than the early (2.2 +/- 0.8 micrograms/g, days 20 to 25) and late luteal phases (1.8 +/- 0.8 micrograms/g, days 26 to 30). Cytosol 17-OHP concentrations also were 3.3 +/- 0.5, 4.3 +/- 0.6, and 3.3 +/- 1.0 micrograms/g in early, midluteal, and late luteal phases, respectively, and was significantly inversely correlated with occupied LH/hCG receptors in midluteal phase. Corpora albicantia had the lowest P (0.3 +/- 0.05 microgram/g) and 17-OHP (0.9 +/- 0.6 micrograms/g) concentrations. Cytosol P and 17-OHP may therefore reflect the balance between the luteal cell production and secretion, whereas the amount of occupied and unoccupied LH/hCG receptors may partially explain the relationship between LH and P secretion.


A stable Na+/H+ antiporter of thermophilic bacterium PS3.
As a first step in the isolation of a stable Na+/H+ antiporter, its reaction in sonicated membrane vesicles of thermophilic bacterium PS3 has been characterized. The sonicated vesicles showed quenching of quinacrine fluorescence in either NADH oxidation or ATP hydrolysis. The quenching was reversed by the addition of Na+, Li+, Mn2+, Cd2+, and Co2+, but not of choline+ or Ca2+, regardless of their counter anions. 22Na+ was taken up into the vesicles by NADH oxidation, and the 22Na+ uptake was inhibited by the addition of an uncoupler. H+ release was observed on addition of Na+ to sonicated vesicles. The magnitude of the pH difference across the membrane induced by NADH oxidation was constant at pH 7.0 to 9.1, but the Na+/H+ antiport was affected by the pH of the medium (optimum pH-8.5). The Km's of the antiporter for Na+ and Li+ were 2.5 and 0.1 mM, respectively, but the Vmax values for the two ions were the same at pH 8.0. In the presence of Li+, no further decrease of fluorescence quenching was observed on addition of Na+ and vice versa. The Na+/H+ antiporter activity in PS3 was stable at 70 degrees C, and the optimum temperature for activity was 55-60 degrees C. In contrast to mesophilic cation/H+ antiporters, this antiporter was not inhibited by a thiol reagent.


Machine learning prediction of mortality in Acute Myocardial Infarction.
Acute Myocardial Infarction (AMI) is the leading cause of death in Portugal and globally. The present investigation created a model based on machine learning for predictive analysis of mortality in patients with AMI upon admission, using different variables to analyse their impact on predictive models. Three experiments were built for mortality in AMI in a Portuguese hospital between 2013 and 2015 using various machine learning techniques. The three experiments differed in the number and type of variables used. We used a discharged patients' episodes database, including administrative data, laboratory data, and cardiac and physiologic test results, whose primary diagnosis was AMI. Results show that for Experiment 1, Stochastic Gradient Descent was more suitable than the other classification models, with a classification accuracy of 80%, a recall of 77%, and a discriminatory capacity with an AUC of 79%. Adding new variables to the models increased AUC in Experiment 2 to 81% for the Support Vector Machine method. In Experiment 3, we obtained an AUC, in Stochastic Gradient Descent, of 88% and a recall of 80%. These results were obtained when applying feature selection and the SMOTE technique to overcome imbalanced data. Our results show that the introduction of new variables, namely laboratory data, impacts the performance of the methods, reinforcing the premise that no single approach is adapted to all situations regarding AMI mortality prediction. Instead, they must be selected, considering the context and the information available. Integrating Artificial Intelligence (AI) and machine learning with clinical decision-making can transform care, making clinical practice more efficient, faster, personalised, and effective. AI emerges as an alternative to traditional models since it has the potential to explore large amounts of information automatically and systematically.


Reciprocal Interplay Between Astrocytes and CD4+ Cells Affects Blood-Brain Barrier and Neuronal Function in Response to β Amyloid.
Background: In Alzheimer's disease (AD) neuronal degeneration is associated with gliosis and infiltration of peripheral blood mononuclear cells (PBMCs), which participate in neuroinflammation. Defects at the blood-brain barrier (BBB) facilitate PBMCs migration towards the central nervous system (CNS) and in particular CD4+ T cells have been found in areas severely affected in AD. However, the role of T cells, once they migrate into the CNS, is not well defined. CD4+ cells interact with astrocytes able to release several factors and cytokines that can modulate T cell polarization; similarly, astrocytic properties are modulated after interaction with T cells. Methods: In in vitro models, astrocytes were primed with β-amyloid (Aβ; 2.5 μM, 5 h) and then co-cultured with magnetically isolated CD4+ cells. Cytokines expression was evaluated both in co-cultured CD4+ cells and astrocytes. The effects of this crosstalk were further evaluated by co-culturing CD4+ cells with the neuronal-like SH-SY5Y cell line and astrocytes with endothelial cells. Results: The pattern of cytokines and trophic factors expressed by CD4+ cells were strongly modulated in the presence of Aβ-primed astrocytes. Specifically, the percentage of IL-4+ and IFNγ+ CD4+ cells was significantly increased and reduced, respectively. Further, increased BDNF mRNA levels were observed in CD4+ cells. When SH-SY5Y cells were co-cultured with astrocyte-conditioned CD4+ cells and exposed to Aβ, the reduction of the presynaptic protein synaptophysin was prevented with a BDNF-dependent mechanism. In astrocytes co-cultured with CD4+ cells, reduced mRNA levels of inflammatory cytokines and VEGF were observed. This was paralleled by the prevention of the reduction of claudin-5 when astrocytes were co-cultured with endothelial cells. Conclusion: Following Aβ exposure, there exists reciprocal crosstalk between infiltrating peripheral cells and astrocytes that in turn affects not only endothelial function and thus BBB properties, but also neuronal behavior. Since astrocytes are the first cells that lymphocytes interact with and are among the principal players in neuroinflammation occurring in AD, understanding this crosstalk may disclose new potential targets of intervention in the treatment of neurodegeneration.


Breast Cancer Risk and Human Papillomavirus Infection: A Bradford Hill Criteria Based Evaluation.
The association between human papillomavirus (HPV) and human breast cancer (BC) has already been thoroughly studied worldwide with contradictory findings. Although the researchers have tried to minimize the conflict using statistical meta-analysis because of its shortcomings, there is still a need to evaluate the correlation between HPV and BC using any additional method. This study was launched to investigate the correlation between HPV and BC through the application of Bradford Hill criteria postulates. Population-wide studies associating HPV with BC were searched using the PubMed database. Then, the information of HPV burden in BC, normal/benign samples was analyzed, and ultimately Bradford Hill criteria postulates were applied on the collected evidence to explore the relationship between HPV and BC. In addition, to make the outcomes more authentic, we also reviewed the methodologies of previous studies to address the propensity of false results. After a careful evaluation of the obtained data against major Bradford Hill criteria postulates, it was noted that all these postulates, including strength, consistency, biological gradient, temporality, plausibility, experiment, specificity, and analogy were not fulfilled. The results of the present study have failed to establish a causal association between HPV and BC, but they did suggest HPV as a cause-effective agent or at least a co-participant in the pathogenesis of BC. Because of the weakness of association, particularly the lack of consistency between studies and the lack of effect specificity, more research into Bradford Hill criteria postulates is required.


Isolation of antibiotic-resistant bacteria in biogas digestate and their susceptibility to antibiotics.
Antibiotics are widely used to prevent and treat diseases and promote animal growth in the livestock industry, and therefore antibiotic residues can end up in biogas digestate from processes treating animal manure (AM) and food waste (FW). These digestates represent a potential source of spread of antimicrobial resistance (AMR) when used as fertilisers. This study evaluated AMR risks associated with biogas digestates from two processes, using AM and FW as substrate, by isolation and identification of antibiotic-resistant bacteria (ARB) and testing their susceptibility to different antibiotics. ARB from the digestates were isolated by selective plating. The antibiotic susceptibility profile of isolates was determined using ampicillin, ceftazidime, meropenem, vancomycin, ciprofloxacin, rifampicin, chloramphenicol, clindamycin, erythromycin, tetracycline, gentamicin or sulfamethoxazole/trimethoprim, representing different antibiotic classes with differing mechanisms of action. In total, 30 different bacterial species belonging to seven genera were isolated and classified. Bacillus and closely related genera, including Paenibacillus, Lysinibacillus and Brevibacillus, were the dominant ARB in both digestates. Most of the ARB strains isolated were non-pathogenic and some were even known to be beneficial to plant growth. However, some were potentially pathogenic, such as an isolate identified as Bacillus cereus. Many of the isolated species showed multi resistance and the AM digestate and FW digestate both contain bacterial species resistant to all antibiotics tested here, except gentamicin. A higher level of resistance was displayed by the FW isolates, which may indicate higher antibiotic pressure in FW compared with AM digestate. Overall, the results indicate a risk of AMR spread when these digestates are used as fertiliser. However, most of the ARB identified are species commonly found in soil, where AMR in many cases is abundant already, so the contribution of digestate-based fertiliser to the spread of AMR may still be very limited.


Leiomyosarcoma of the superior vena cava. A first case with resection.
Leiomysarcomas, rare malignant tumors of the veins, are located predominantly in the inferior vena cava. We report our experience with a leiomyosarcoma in the superior vena cava of a 44-year-old white man. The lesion had been locally excised and then recurred 2 1/2 years later. The recurrent tumor was widely excised and the superior vena cava was repaired with a saphenous vein patch graft. The area of the recurrence was treated with cobalt 60 therapy. Four years later, 6 1/2 years after initial treatment, the patient is alive and well without evidence of recurrence.


Sentinel lymph node biopsy in N+ breast cancer with conversion into N0 after neoadjuvant chemotherapy.
Sentinel lymph node biopsy (SLNB) usefulness in breast carcinoma N+ converted to N0 after neoadjuvant chemotherapy (NC). Descriptive study including 16 females with infiltrating carcinoma with lymphatic metastasis confirmed by biopsy, leaving a metallic marker (MM) in pathological lymph nodes (LN). All patients underwent NC reaching a complete radiological response in LN. Lymphoscintigraphy was performed after 99mTc nanocoloid injection, obtaining planar images and SPECT/CT. Lymphatic drainage and concordance of sentinel node (SN) with MM was analyzed. SN was visualized in lymphoscintigraphy in 93.7% of cases. The SN coincided with the MM in 12/15 cases on SPECT/CT. The SLNB technique was completed on 14/16 patients, intraoperatively locating the GC in all of them. The SN was negative in 10 cases, 3 cases presented macrometastases and 1 micrometastases. Axillary lymphadenectomy (AL) was performed in a case of macrometastasis with>15,000cp/μARNm CK-19, absence of drainage and in one case that showed no coincidence with the MM due different Berg's level location. These last two cases presented lymph node metastasis. In the other two cases with not coincidence between the SN and the MM, a total of 4 lymph nodes were removed, showing no evidence of metastasis. Patients without AL were followed up for an average of 10 months (range 6-17), with no evidence of lymph node involvement. SLNB in breast cancer with conversion into N0 after neoadjuvant treatment is a technique with good results and a low false negative rate.


Unraveling the origin of glucose mediated disparate proliferation dynamics of cancer stem cells.
Cancer stem cells (CSCs) often switch on their self-renewal programming aggressively to cause a relapse of cancer. Intriguingly, glucose triggers the proliferation propensities in CSCs by controlling the expression of the key transcription factor-like Nanog. However, the factors that critically govern this glucose-stimulated proliferation dynamics of CSCs remain elusive. Herein, by proposing a mathematical model of glucose-mediated Nanog regulation, we showed that the differential proliferation behavior of CSCs and cell-type similar to CSCs can be explained by considering the experimentally observed varied expression levels of key positive (STAT3) and negative (p53) regulators of Nanog. Our model reconciles various experimental observations and predicts ways to fine-tune the proliferation dynamics of these cell types in a context-dependent manner. In future, these modeling insights will be useful in developing improved therapeutic strategies to get rid of harmful CSCs.


PM2.5 induced apoptosis in endothelial cell through the activation of the p53-bax-caspase pathway.
Exposure to airborne fine particulate matter (PM2.5) is associated with cardiovascular diseases (CVDs). Nevertheless, a comprehensive understanding of the underlying biological mechanisms by which PM2.5 exposure induces or aggravates CVDs remain insufficiently clear. In the present study, the flow cytometry was employed to investigate the apoptosis of human umbilical vein endothelial cells (HUVECs) induced by PM2.5 in culture. The underlying apoptotic pathway was also studied through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that PM2.5 could significantly induce the apoptosis of HUVECs at the tested concentrations (0.2, 1, 5, 25 μg mL-1), compared with the negative control (p < 0.05, p < 0.01). The apoptotic rate of HUVECs increased with the elevating levels of PM2.5 exposure, showing a clear dose-effect relationship. Moreover, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3 and PARP, were also observed with the increasing concentrations of PM2.5 administration in the western blot, indicating that the intracellular approach of apoptosis, the p53-Bax-caspases pathway, is the major way of PM2.5-induced apoptosis in HUVECs. In conclusion, these results suggested that induction of EC apoptosis is an important mechanism by which ambient PM2.5 exposure poses adverse effects on the cardiovascular system.


The association between occupational stress and depressive symptoms and the mediating role of psychological capital among Chinese university teachers: a cross-sectional study.
Depression is a major public health problem that affects both individuals and society. Previous studies report that university teachers are particularly susceptible to high levels of occupational stress and depressive symptoms. The aims of this study were to explore the association between occupational stress and depressive symptoms in a group of university teachers, and assess the mediating role of psychological capital between these variables. A cross-sectional study was performed between November 2013 and January 2014. Teachers from six universities were randomly sampled in Shenyang. The Center for Epidemiologic Studies Depression Scale, effort-reward imbalance scale, and psychological capital questionnaire (PCQ-24), as well as questions about demographic and working factors, were administered in questionnaires distributed to 1,500 university teachers. Completed questionnaires were received from 1,210 participants. Hierarchical linear regression analysis was used to examine the mediating role of psychological capital. In the present study, 58.9% (95% CI (Confidence Intervals): 56.1% to 61.7%) of university teachers had a CES-D score equal to or above the cut-off of 16. Both effort-reward ratio (ERR) and scores of over-commitment were positively associated with depressive symptoms, whereas psychological capital was negatively associated with depressive symptoms among university teachers. Psychological capital partially mediated the relationship between occupational stress and depressive symptoms. Among Chinese university teachers, occupational stress may be a risk factor for depressive symptoms, whereas psychological capital might be protective against depressive symptoms. Our results suggest that college administrators could support the development of psychological capital in their staff to alleviate depressive symptoms.


Abnormal immune function in malignant hypertension.
To investigate the extent to which the immune system is influenced in patients with previous malignant hypertension. Twenty-three patients with malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had been instituted they were investigated to establish the function of the cellular immune system (number of T lymphocytes and the proliferative response to T-cell mitogens), human leucocyte antigens A, B and C and frequency of autoantibodies. The numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte-stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin and concanavalin-A. Autoantibodies were determined with immunoassay techniques and leucocyte A, B and C antigens with a lymphocytotoxicity test. The frequency of T lymphocytes and their baseline thymidine incorporation were significantly depressed in patients with previously malignant hypertension compared with control subjects. The group with malignant hypertension also had a decreased proliferative response to concanavalin-A but not to phytohaemagglutinin, and they had an increased frequency of antinuclear antibodies. Human leucocyte antigen B15 tended to occur more frequently in patients with malignant and non-malignant hypertension than in control subjects, especially if a family history of hypertension was taken into consideration. The results from the present study indicate that immune mechanisms are involved in malignant hypertension, either secondary to the vascular damage or as a primary abnormality.


Development of improved strain in species of Pleurotus by gamma irradiation.
The oyster mushroom (Pleurotus spp.) is the second important edible mushroom in the world, with 19 per cent contribution to total mushroom production (Sharma et al., Mushroom Res 26(2):111-120, 2017). The cultivated mushrooms face the problems like loss of genetic diversity and strain degeneration (Wang et al., Curr Microbiol 65(4):424-431, 2012). Thus to enhance the productivity within short duration, three species of Pleurotus namely Pleurotus djamor, Pleurotus florida and Pleurotus ostreatus were gamma irradiated at 20 and 25 Gy at 9.779 kGy/h and performance of mutants followed by three generation of selection in paddy straw substrate were observed. Biological efficiency (BE) of P. djamor mutants irradiated at 20 Gy was increased by 9.25 per cent. The number of days taken for primordial initiation was also reduced by 1 day compared to P. djamor. P. florida irradiated at 25 Gy recorded increase in sporocarp size over P. florida. The biological efficiency of P. ostreatus irradiated at 25 Gy was improved by 12.89 per cent and there was earliness in primordial initiation by 3 days compared to P. ostreatus. The polymorphism per cent was analysed by Random Amplified Polymorphic DNA (RAPD) and revealed that P. djamor, P. florida and P. ostreatus had 16.70%, 25% and 22% polymorphism with their respective improved strains.


Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal.
The mouse insulin-like growth factor type 2 receptor (Igf2r) is imprinted and expressed exclusively from the maternally inherited chromosome. To investigate whether methylation could function as the imprinting signal, we have cloned 130 kb from the Igf2r locus and searched for sequences methylated in a parental-specific manner. Two regions have been identified: region 1 contains the start of transcription and is methylated only on the silent paternal chromosome; region 2 is contained in an intron and is methylated only on the expressed maternal chromosome. Methylation of region 1 is acquired after fertilization, in contrast with the methylation of region 2, which is inherited from the female gamete. Methylation of region 2 may mark the maternal Igf2r locus in a manner that could act as an imprinting signal. These data suggest that the expressed locus carries a potential imprinting signal and imply that methylation is necessary for expression of the Igf2r gene.


Cooperative reorganization of a 420 subunit virus capsid.
The complex protein capsids of many viruses exhibit dramatic reorganizations at critical stages in their life-cycle. Here, time-resolved solution X-ray scattering was used to study a dynamic, large-scale conformational maturation of the 420 subunit, 13 MDa, icosahedrally symmetric HK97 bacteriophage capsid. Isoscattering points in the time-resolved scattering patterns and singular value decomposition revealed that the expansion occurs as a cooperative, two-state reaction. The analysis demonstrates that the population shift from Prohead-II to Expansion Intermediate I, EI-I (60 A larger than Prohead-II) occurs in minutes, but does not reveal the time required for individual transitions that occur stochastically. Any intermediate forms that may be traversed during this conversion are unstable and do not constitute an appreciable population of the ensemble of particles. In an energetic landscape view, particles must undergo an energy barrier-crossing event in order to successfully convert from Prohead-II to EI-I. This implies that the particles "hop" over the energy barrier stochastically as they individually attain an expansion-active state. Interestingly, systematic deviations from single-exponential kinetics were observed for the population shift. This may indicate that in undergoing the irreversible conversion from Prohead-II to EI-I, particles are subject to a complex energy landscape that links the initial and final particle forms.


[The future of inflammatory bowel disease from the perspective of Digestive Disease Week 2012].
The new information presented in Digestive Disease Week has allowed us to speculate on the future of inflammatory bowel disease. Manipulation of diet and the microbioma will probably play an increasingly important role in the treatment of this disease and, in the long term, in its prevention. Biological agents will probably be used earlier and more widely; new information on levels of biological agents, mucosal healing and new comparative studies will also allow these agents to be used in a more precise and personalized way. In addition to infliximab, adalimumab, natalizumab and certolizumab, other biological agents will be employed; among the first of these to be used will be ustekinumab, golimumab and vedolizumab. In the near future, biological agents will be used as frequently in ulcerative colitis as in Crohn's disease. New healthcare models will be developed that will progressively include greater participation among patients and nurses. The ability to predict new diagnostic and prognostic models will allow decisions to be more individualized.


Localization of the renin-angiotensin system components to the skeletal muscle microcirculation.
Local renin-angiotensin systems have been found in various organs and tissues throughout the body. The studies described here tested the hypothesis that a fully functional renin-angiotensin system exists in the skeletal muscle microvasculature. The purpose of this study was to localize the components and products of the system to the skeletal muscle microvasculature. The presence of mRNA and protein for renin and angiotensinogen was shown by reverse transcriptase polymerase chain reaction analysis and immunohistochemistry, respectively. Angiotensin II concentration in isolated microvessels was measured by high-performance liquid chromatography separation and radioimmunoassay. Renin and angiotensinogen mRNA was detected from isolated cremaster microvessels. Specific staining for renin and angiotensinogen protein was found throughout the walls of microvessels. The concentration of the angiotensin II in the microvessels (104.3 +/- 18.1 fmol/g) was found to be higher than the concentration of angiotensin II in the plasma (8.7 +/- 1.2 fmol/mL) of the same animals. Also, it was shown that the microvessel angiotensin II concentrations in spontaneously hypertensive rats were higher than in Sprague-Dawley rats. The current study demonstrates that within the skeletal muscle microvessels, the components and products necessary for a local renin-angiotensin system are present, but does not rule out the possibility of interaction between circulating and tissue renin-angiotensin systems.


Overcoming Mfsd2a-Mediated Low Transcytosis to Boost Nanoparticle Delivery to Brain for Chemotherapy of Brain Metastases.
Microvessels of the blood-brain barrier (BBB) exclusively express the major facilitator superfamily domain-containing protein 2a (Mfsd2a), which is the key transporter for docosahexaenoic acid uptake into the brain. Mfsd2a suppresses caveolae-mediated transcytosis to regulate BBB transcellular permeability via controlling lipid composition of BBB endothelial cells. It is speculated that Mfsd2a can restrain BBB crossing efficiency and brain accumulation efficiency of brain-targeting drug delivery systems, which penetrate the BBB often through the receptor-mediated transcytosis pathway. Transcytosis across the BBB is a crucial bottleneck for targeted chemotherapy of brain metastases. To overcome this issue, a pair of priming nanoparticles (NPs) and following drug-loaded NPs are designed. Tunicamycin-(TM)-loaded transcytosis-targeting-peptide-(TTP)-decorated NPs (TM@TTP) are used to boost BBB transcytosis via inhibiting Mfsd2a. Doxorubicin (DOX)-loaded TTP and CD44-specific hyaluronic acid (HA)-comodified NPs (DOX@TTP-HA) are designed as following drug-loaded NPs. The brain accumulation efficacy of following DOX@TTP-HA with priming is 4.30-fold higher than that without priming through the enhanced transcytosis pathway rather than the tight junction opening. Effective BBB crossing and brain accumulation, selective tumor uptake, excellent antitumor efficacy, and low hepatotoxicity are achieved by TM@TTP and DOX@TTP-HA, suggesting this tactic as a significant therapeutic strategy against breast cancer brain metastases.


Clinical Manifestations and Long-Term Outcomes of Eosinophilic Granulomatosis With Polyangiitis in North America.
To describe clinical manifestations and outcomes in patients with eosinophilic granulomatosis with polyangiitis (EGPA) in North America. Analysis of patients aged 18 years or older who fulfilled the 1990 American College of Rheumatology Classification Criteria for EGPA enrolled in the Vasculitis Clinical Research Consortium from 2003 to 2019. Main clinical characteristics, treatments, outcomes, and accumulated damage were studied. The cohort included 354 patients; 59% female; age at diagnosis of 50.0 (±14) years; 39% were antineutrophil cytoplasm antibody (ANCA) positive. Time from diagnosis to last follow-up was 7.0 (±6.2) years; 49.4% had one or more relapse. Patients positive for ANCA more commonly had neurological and kidney involvement when compared with patients negative for ANCA, who had more cardiac and lung manifestations. At last study visit, only 35 (12.6%) patients had been off all therapy for more than 2 years during their follow-up. The overall mortality rate was 4.0% and did not differ by ANCA status or cyclophosphamide use. Scores on the Vasculitis Damage Index (VDI) for 134 patients with two or more visits and more than 1 year of follow-up increased from 1.7 (±1.8) at enrollment (3.7 [±5.1] years after diagnosis) to 3.35 (±2.1) at last follow-up (7.5 [±5.8] years after diagnosis), mainly represented by chronic asthma (67.5%), peripheral neuropathy (49.6%), and chronic sinusitis (31.3%). Longer duration of glucocorticoid use and relapse were associated with higher VDI scores. This analysis describes the many clinical manifestations and varied outcomes of EGPA and highlights the ongoing need to attain more sustained, long-term remission to limit the accrual of disease-related damage.


Chitosan reduced in-situ synthesis of gold nanoparticles on paper towards fabricating highly sensitive, stable uniform SERS substrates for sensing applications.
Surface-Enhanced Raman Spectroscopy (SERS) is a powerful surface-sensitive technique for molecular analysis. Its use is limited due to high cost, non-flexible rigid substrates such as silicon, alumina or glass and less reproducibility due to non-uniform surface. Recently, paper-based SERS substrates, a low-cost and highly flexible alternative, received significant attention. We report here a rapid, inexpensive method for chitosan-reduced, in-situ synthesis of gold nanoparticles (GNPs) on paper devices towards direct utilization as SERS substrates. GNPs have been prepared by reducing chloroauric acid with chitosan as a reducing and capping reagent on the cellulose-based paper surface at 100 °C, under the saturated humidity condition (100 % humidity). GNPs thus obtained were uniformly distributed on the surface and had fairly uniform particle size with a diameter of 10 ± 2 nm. Substrate coverage of resulting GNPs directly depended on the precursor's ratio, temperature and reaction time. Techniques such as TEM, SEM, and FE-SEM were utilized to determine the shape, size, and distribution of GNPs on paper substrate. SERS substrate produced by this simple, rapid, reproducible and robust method of chitosan-reduced, in situ synthesis of GNPs, showed exceptional performance and long-term stability, with a detection limit of up to 1 pM concentration of test analyte, R6G. Present paper-based SERS substrates are cost-effective, reproducible, flexible, and suitable for field applications.


Marinobufagenin, an endogenous ligand of alpha-1 sodium pump, is a marker of congestive heart failure severity.
A reduced cardiac output in chronic heart failure (CHF) evokes renal NaCl and water retention, and, therefore, activates mechanisms promoting natriuresis. Atrial natriuretic peptide (ANP) is one such factor. We hypothesized that another NaCl sensitive endogenous natriuretic factor, i.e., marinobufagenin (MBG), a specific ligand of the alpha-1 subunit of Na/K ATPase (the main kidney isoform) and also a vasoconstrictor and cardiotonic substance, would be elevated in CHF patients in a graded manner with the severity of CHF. We measured the plasma levels of MBG, alpha-hANP, ouabain-like compound (OLC) and left ventricular (LV) volumes and ejection fraction in 23 consecutive hypertensive male patients with CHF. Plasma MBG levels exhibited progressive increases (0.59 +/- 0.15, 1.08 +/- 0.20, 1.35 +/- 0.17 and 1.88 +/- 0.05 nmol/l NYHA 1-4, respectively) and paralleled the changes of alpha-hANP. Conversely, plasma OLC did not exhibit such increases. Plasma MBG correlated with alpha-hANP (r = 0.82; P < 0.0001). Both MBG and alpha-hANP correlated with LV systolic (r = 0.55 and r = 0.47; P < 0.01) diameter and inversely with ejection fraction (r = -0.73 and r = -0.60; P < 0.01). OLC did not exhibit correlations with alpha-hANP or LV volumes, but positively correlated with systolic brachial blood pressure and with pulse pressure. In CHF, MBG exhibits progressive increases similar to ANP, varies with CHF severity and correlates with LV systolic function. We hypothesize, that, in CHF, the concurrent production of these two natriuretic hormones, a vasorelaxant, ANP, and a vasoconstrictor, MBG, potentiate each other's natriuretic effects, but may offset their vasoactive actions.


Pigeons learn the concept of an "A".
Pigeons learned to discriminate between "A"S and "2"s in eighteen different typefaces. They subsequently showed excellent transfer to twenty-two typefaces that they had not previously seen; one pigeon was tested with handwritten letters and responded correctly to them also. Pigeons' responses to "A's and "2's with parts removed suggested that their performance was controlled by several features, none of which alone could be considered necessary or sufficient. A test in which birds were shown other letters of the alphabet supported this conclusion. It appears that the original discrimination was learned as what Ryle calls a "polymorphous concept".


The growing challenge of obesity and cancer: an inflammatory issue.
The prevalence of obesity, an established risk factor for many cancers, has risen steadily for the past several decades in the United States and in many parts of the world. This review synthesizes the evidence on key biological mechanisms underlying the obesity-cancer link, with particular emphasis on the impact of energy balance modulation, such as diet-induced obesity and calorie restriction, on growth factor signaling pathways and inflammatory processes. Particular attention is placed on the proinflammatory environment associated with the obese state, specifically highlighting the involvement of obesity-associated hormones/growth factors in crosstalk between macrophages, adipocytes, and epithelial cells in many cancers. Understanding the contribution of obesity to growth factor signaling and chronic inflammation provides mechanistic targets for disrupting the obesity-cancer link.


Technical Feasibility on the Use of Optical Coherence Tomography in the Evaluation of Pediatric Pulmonary Venous Stenosis.
Pulmonary vein stenosis (PVS) in children is a morbid disease and limited progress has been made in improving outcomes for this heterogenous group of patients. Evaluation is currently limited to imaging techniques that fail to provide an adequate overview of the intraluminal and luminal pathology perpetuating our limited understanding of this condition. Optical coherence tomography (OCT) is an imaging modality which provides intraluminal profiling with microstructural detail through optical reflective technology. We sought to evaluate whether its use was technically feasible in pediatric PVS and whether the imaging data provided potentially useful outputs for clinical utility. Eleven patients were prospectively selected from our cardiac catheterization for OCT evaluation of their pulmonary veins (PV) during elective catheterization for PVS. Measurements were taken both pre and post intervention using both manual and automated tools. Stent morphology was characterized. Eleven patients had evaluation of 34 pulmonary veins, with 7 patients having more than one assessment, for a total of 25 overall catheterizations. Most patients were female (75%). Median age at cardiac catheterization was 35 months (range 5-45 months). Median weight of subjects was 10.6 kg (3.7-14.2) with a median BSA documented at 0.505 m2 (0.21-0.57). Median number of pulmonary veins involved was 3, (range 1-5 veins) and median contrast volume of 2.9 mL/kg (0.7-3.7) given. Median radiation dose (DAP) was 6095 µGy·cm2 (1670-12,400). Median number of previous cardiac catheterizations was 7 (range 1-11). All of the vessels with a diameter < 5 mm were adequately visualized. Of all the OCT images acquired, in 15 vessels (44%) contrast was used to clear the vessels from blood as an angiogram was required at the time, in the other 19 vessels (56%), saline was used with adequate imaging. There were no complications related to OCT. OCT is technically feasible to use in pediatric patients without any directly related complications. It provides intraluminal anatomy in children with both native and treated pulmonary venous stenosis when vessel size is less than 5 mm.


Longitudinal associations between neighbourhood physical environments and depressive symptoms of older adults in Hong Kong: The moderating effects of terrain slope and declining functional abilities.
Little is known about the accumulative impacts of neighbourhood physical environments on older adults' depressive symptoms over time. Based on a cohort study of 2081 older adults in Hong Kong, this study examined longitudinal relationships between neighbourhood physical environments and depressive symptoms among older adults, with a particular focus on the moderating effects of terrain slope and individual functional ability using latent growth curve modelling. Results indicated that the availability of community centres and passive leisure facilities reduced depressive symptoms over time. The protective effects of residential surrounding greenness on depressive symptoms among older adults differed by the terrain slope types. Longitudinal associations between neighbourhood physical environments and depressive symptoms varied between older adults with and without functional limitations. This study has implications for the Ecological Theory of Ageing by identifying the dynamic interplay of environment demands and individual functional ability. Planning policies for building age-friendly neighbourhoods are discussed.


Use of magnetic beads to study the interaction of ristocetin with peptides and bacteria.
We aimed to develop and validate sensitive fluorescence techniques to assess the binding of magnetic microbeads derivatized with ristocetin from Amycolatopsis lurida to carboxyfluorescein-labeled D-Ala-D-Ala-D-Ala and in competition with Staphylococcus aureus bacteria. Glycopeptide antibiotics have been widely used to treat bacterial infections. However, new antibiotics are needed because of growing bacterial resistance and serious side effects. To screen potential candidates for new antibiotics, there is a great demand for sensitive, fast and inexpensive techniques to analyze the interactions between these molecules and bacterial cells. Fluorometry, an in-house fluorescent instrument and fluorescence microscopy were used to determine binding constants of 2.75 × 10(4), 2.21 × 10(4) and 0.81 × 10(4) M(-1), respectively, for the interaction between ristocetin and the labeled peptide. The methods detailed herein have been successfully applied to assess the binding of carboxyfluorescein- labeled D-Ala-D-Ala-D-Ala to ristocetin on microspheres. The magnetic bead-based immunoassay could be used to detect bacteria at low concentrations.


PMN chemotactic inhibition associated with a cryoglobulin.
A child with recurrent pyogenic infections, eczema, markedly elevated serum concentrations IgA, and totally absent PMN chemotactic acticity is described. The chemotactic defect was characterized as a humoral inhibitor present in serumand plasma, directed toward autologous as well as homologous PMN's. Immunochemical studies revealed the purified inhibitor to be a cryoglobulin composed of an IgM-IgA complex. Incubation of the cryoglobulin complex with PMN's resulted in a quantitative dose-response curve.


Cell division cycle 42 positively correlates with T helper 2 cytokine, effusion viscosity, and hearing loss degree in otitis media with effusion patients.
Cell division cycle 42 (CDC42) participates in the pathogenesis of some T-cell-mediated inflammatory diseases via regulating CD4+ T-cell differentiation and inflammation response. This study aimed to evaluate the correlation of CDC42 and T helper (Th)1/Th2 cytokines with disease risk, effusion viscosity, and hearing loss degree of otitis media with effusion (OME). CDC42, interleukin (IL)-4, and interferon-gamma (IFN-γ) in effusion and serum of 78 OME patients were determined by enzyme-linked immunosorbent assay. Besides, the effusion (irrigating fluid) and serum samples of 30 controls (adenoid hypertrophy patients without OME) were also obtained for CDC42, IL-4, and IFN-γ determination. Effusion CDC42 and IL-4 were elevated in OME patients compared with controls (both p < 0.001). Effusion CDC42 was positively correlated with effusion IL-4 in OME patients (p = 0.004) and controls (p = 0.012) but was not related to effusion IFN-γ (both p > 0.050). Additionally, effusion CDC42 (p = 0.025) and IL-4 (p = 0.023) were increased in OME patients with mucoid effusion compared to patients with serous effusion, while effusion IFN-γ was of no difference between those patients (p = 0.215). Meanwhile, elevated effusion CDC42 (p = 0.012) and IL-4 (p = 0.033) were linked with increased hearing loss degrees, whereas effusion IFN-γ was not related to hearing loss degrees (p = 0.057). Moreover, the findings of serum CDC42, IL-4, and IFN-γ showed similar trends as effusion ones; nonetheless, their correlation with disease features was generally weaker. OME patients present with elevated CDC42 and IL-4 levels; the latter factors are intercorrelated and positively associate with effusion viscosity and hearing loss degree.


Prevalence and molecular epidemiology of Canine parvovirus 2 in diarrheic dogs in Colombia, South America: A possible new CPV-2a is emerging?
Since its identification in 1978, Canine parvovirus type 2 (CPV-2) has been considered a pathogen of great importance in the canine population because it causes severe enteritis with high mortality rates in pups. CPV-2 is a virus belonging to the family Parvoviridae. Currently, there are three described antigenic variants (CPV-2a, CPV-2b, and CPV-2c). CPV-2c is an emerging virus that is seen as a global health hazard. The objective of this work was to confirm the presence of CPV-2 in dogs with acute gastroenteritis compatible with parvovirus and to molecularly characterize the antigenic variants circulating in two regions of Colombia. An analytical cross-sectional study was conducted with fecal samples collected from 71 dogs showing signs of acute diarrhea. The samples were processed and polymerase chain reaction (PCR), restriction fragment length polymorphism analysis (RFLP), sequencing and phylogenetic analysis was performed to detect and characterize CPV. A total of 70.42% of the individuals were confirmed positive for CPV-2. Statistically differences were found in the presentation of CPV-2 between the evaluated regions. Phylogenetic analyses confirmed the presence of the antigenic variants CPV-2a/2b. Moreover, we found the presence of two conserved substitutions Asn428Asp and Ala514Ser in the VP2 protein suggesting the presence of a possible new CPV-2a variant circulating in Colombia. This study demonstrates the importance of the CPV 2a/2b in the region and highlights the importance of performing molecular studies for the early detection of new antigenic variants of CPV-2.


The adult rat hippocampal slice revisited with multi-electrode arrays.
The multi-electrode arrays (MEA) technology for the recording of brain slices is available for more than 10 years. However, despite its relative simplicity, this recording technique is not widely used in academic or pharmaceutical research laboratories. We illustrate here that MEA provide multiple possibilities to investigate some network physiological properties as well as to evaluate the pharmacological effects of compounds. We first document that MEA allow to trigger and to record conventional FP which are inhibited by the block of action potential propagation (with 500 nM TTX). FP recorded with MEA are sensitive to ionic substitutions, to ionotropic glutamate receptor antagonists (CNQX or NBQX) and to energetic failure. Second, we illustrate that different "classical" protocols (paired-pulse, LTP, chemical LTD), revealing synaptic plasticity mechanisms, could be performed. Third, we document that MEA allow spatial and temporal discriminations for the effects of known pharmacological compounds such as competitive antagonist (gabazine, bicuculline) and allosteric modulators (steroids) of GABA(A) receptors. In conclusion, we illustrate that MEA recordings of adult rat hippocampal slices constitute a powerful and sensitive system to evaluate the effect of molecules on basic synaptic propagation/transmission and on synaptic plasticity processes.


Basal cell carcinoma of scrotum.
Two cases of basal cell carcinoma of the scrotum are reported. Wide local excision of the lesion is all that is necessary as primary treatment because regional lymph node metastases are seldom seen.


[Methodological differences of the physical and computational model approaches].
General principles of modeling, the problem of adequency of models, and the similarity and differences between physical and computational models are discussed.


Median nerve hamartoma: MR imaging using chemical shift techniques.
Magnetic resonance imaging findings of median nerve hamartoma are presented in three patients with palpable wrist masses and median neuropathy. Fat-suppressed T1-weighted images demonstrated adipose tissue separating the neural and fibrous tissue bundles in two of three patients, which results in the distinctive appearance of these tumors on magnetic resonance imaging. Fibrous tissue appeared as enhancing longitudinal bundles within the tumor on gadolinium enhanced fat-suppressed T1-weighted images.


Dosimetric parameters related to occurrence of distant metastases and regional nodal relapse after SBRT for early-stage non-small cell lung cancer.
Previous studies have suggested that the dose immediately outside the PTV may impact the incidence of distant metastases after stereotactic body radiation therapy (SBRT) for patients with early-stage non-small cell lung cancer (NSCLC). In particular, Diamant et al. [1,2] reported a correlation between the mean EQD2 of a 30 mm shell around the PTV and both local control and the rate of distant metastases. In this study, we assess this parameter and others in a series of patients with radiographically presumed or biopsy-proven early-stage NSCLC treated at our institution with stereotactic body radiotherapy (SBRT) between 2017 and 2019. We reviewed the dosimetry, local control, regional nodal relapse, and rate of distant metastases for 304 patients with 325 lesions treated with SBRT at our institution. Dosimetric parameters investigated include the prescribed dose, minimum and mean doses to the PTV, conformity index, and the mean EQD2 to a 30 mm shell around the PTV. Time to each event was defined from date of last fraction of SBRT to date of event, with event-free patients censored at last radiographic follow-up. Univariate (UVA) Cox regression analysis was performed on the collected parameters to assess for correlation with regional nodal relapse and rate of distant metastases. There was no significant correlation between the mean EQD2 dose to a 30 mm shell around the PTV and the rate of distant metastases. On UVA Cox proportional hazards analysis, positive predictors of reduced incidence of distant metastases were PTV <22 cc (vs. ≥22 cc, p = 0.01) and GTV <10 cc (vs. ≥10 cc, p < 0.01), with GTV <10 cc also being a positive predictor of reduced incidence of regional nodal relapse (p < 0.01). In the subset of patients treated with 4-5 fractions, mean EQD2 dose to the 30 mm shell around the PTV ≥21 Gy was associated with increased incidence of distant metastases (HR 2.42, 95% CI 1.06-5.53, p = 0.04), differing from prior data from Diamant et al. CONCLUSIONS: We did not observe a correlation between the rate of distant metastases and dose outside the PTV, as reported by other groups; rather, we noted an opposite trend in patients treated with 4-5 fractions. Our data show additional correlations between distant metastases and tumor size.


A median-Gaussian filtering framework for Moiré pattern noise removal from X-ray microscopy image.
Moiré pattern noise in Scanning Transmission X-ray Microscopy (STXM) imaging introduces significant errors in qualitative and quantitative image analysis. Due to the complex origin of the noise, it is difficult to avoid Moiré pattern noise during the image data acquisition stage. In this paper, we introduce a post-processing method for filtering Moiré pattern noise from STXM images. This method includes a semi-automatic detection of the spectral peaks in the Fourier amplitude spectrum by using a local median filter, and elimination of the spectral noise peaks using a Gaussian notch filter. The proposed median-Gaussian filtering framework shows good results for STXM images with the size of power of two, if such parameters as threshold, sizes of the median and Gaussian filters, and size of the low frequency window, have been properly selected.


If SARS-CoV-2 is blamed for causing meningoencephalitis, the virus must be detected in the CSF.
We have read with interest the article by Watroba and Bryda on a new-born male with SARS-CoV-2 associated meningo-encephalitis, post-inflammatory hydrocephalus and seizures [1]. Neuro-COVID in this patient was treated with a polypragmatic approach, including phenobarbital, acetazolamide, fluconazole, acyclovir, cefotaxime, and vancomycin [1]. The study is appealing but has limitations that raise concerns and should be discussed.


Prevalence and Predictors of Patient Nonadherence to Pharmacological Acute Pain Therapy at Home After Day Surgery: A Prospective Cohort Study.
Good adherence to prescribed analgesics can be crucial to suppress or even prevent acute postoperative pain after day surgery. The aim of this study was to analyze prevalence and predictors of analgesic nonadherence after day surgery. Elective patients scheduled for day surgery were prospectively enrolled from November 2008 to April 2010. Outcome parameters were measured by using questionnaire packages at 2 time points: 1 week preoperatively and 4 days postoperatively. The primary outcome parameter was analgesic nonadherence. Adherence was defined according to the patient's response to the questionnaire item "analgesia use as prescribed": full adherence, "yes"; partial adherence, "yes, sometimes"; nonadherence, "no." Bivariate and multivariate logistic regression analyses were performed to identify predictors of analgesic nonadherence. A total of 1,248 patients were included. The prevalence rates of analgesic nonadherence and partial adherence were 21.6% and 20.0%, respectively, in the total study population but dropped to 9.4% and 19.8%, respectively, in patients with moderate to severe pain. Low postoperative pain intensity and short duration of surgery were the most important predictors of analgesic nonadherence. The most important preoperative predictors for analgesic nonadherence were low preoperative pain intensity, low preoperative expectations of pain, and low fear of short-term effects of surgery. Analgesic nonadherence and partial adherence are common after day surgery but decrease as average pain intensity increases. Patients at risk for analgesic nonadherence can be identified during the preoperative period based on preoperative pain intensity, preoperative expectations of pain, and fear of surgery.


Effect of naloxone on the habituation of novelty-induced hypoalgesia: the collateral inhibition hypothesis revisited.
Repeated daily administration of the opiate receptor antagonist naloxone prior to hotplate tests provokes longer paw-lick latencies by attenuating the habituation of novelty-induced hypoalgesia. This hypoalgesia has been found to persist when pain tests are subsequently conducted following saline administration. The present experiments were conducted to determine whether the substrates mediating the hypoalgesia observed during naloxone and saline tests are similar or distinct. Neither the hypoalgesia observed during naloxone nor saline tests were affected by the induction of tolerance to the hypoalgesic effect of morphine, suggesting that both effects are mediated by nonopioid antinociceptive mechanisms. Previous work from our laboratory demonstrated that the hypoalgesia observed during naloxone tests is inhibited by clonidine, enhanced by yohimbine, and unaffected by prazosin and phentolamine. In the present article, we report a similar pattern of results for the hypoalgesia observed during saline tests. It is concluded that the substrates mediating both effects are similar. The results are discussed in relation to the possibility that an opioid substrate involved in habituative learning may be inhibitory on a nonopioid antinociceptive substrate.


Cytotoxicity, cell cycle arrest, and apoptosis in breast cancer cell lines exposed to an extract of the seed kernel of Mangifera pajang (bambangan).
An extract of Mangifera pajang kernel has been previously found to contain a high content of antioxidant phytochemicals. The present research was conducted to investigate the anticancer potential of this kernel extract. The results showed that the kernel crude extract induced cytotoxicity in MCF-7 (hormone-dependent breast cancer) cells and MDA-MB-231 (non-hormone dependent breast cancer) cells with IC50 values of 23 and 30.5 microg/ml, respectively. The kernel extract induced cell cycle arrest in MCF-7 cells at the sub-G1 (apoptosis) phase of the cell cycle in a time-dependent manner. For MDA-MB-231 cells, the kernel extract induced strong G2-M arrest in cell cycle progression at 24h, resulting in substantial sub-G1 (apoptosis) arrest after 48 and 72 h of incubation. Staining with Annexin V-FITC and propidium iodide revealed that this apoptosis occurred early in both cell types, 36 h for MCF-7 cells and 24 h for MDA-MB-231 cells, with 14.0% and 16.5% of the cells respectively undergoing apoptosis at these times. This apoptosis appeared to be dependent on caspase-2 and -3 in MCF-7 cells, and on caspase-2, -3 and -9 in MDA-MB-231 cells. These findings suggest that M. pajang kernel extract has potential as a potent cytotoxic agent against breast cancer cell lines.


Sensory characteristics of foods: new evaluation techniques.
New product development requires the integration of sensory attributes including product taste, texture, and appearance with consumer attitudes and health biases. Both sensory and attitudinal variables determine food preferences, product purchase and food consumption. This review paper describes novel mathematical procedures that allow for study of real foods rather than model systems. Application of the Response Surface Method (RSM) to sensory evaluation of salted snacks is described.


Simultaneous MR acquisition of arterial and brain signal-time curves.
Regional cerebral blood flow (rCBF) provides important information about local neuronal functional and cerebrovascular status. Determination of rCBF requires sequential measurements of tracer concentration in arterial blood and brain tissue unless the tracer is trapped in the brain in proportion to rCBF. Since gadopentate dimeglumine is not trapped within brain tissue, we have developed the simultaneous dual FLASH pulse sequence (SDFLASH) which sequentially measures the MR signal change in both the internal carotid artery and brain parenchyma simultaneously during the passage of a bolus of paramagnetic contrast material.