Oncologist's knowledge and implementation of guidelines for breakthrough cancer pain in Spain: CONOCE study.
Breakthrough cancer pain (BTcP) has been shown to be a prevalent and poor prognostic factor for oncologic patients, which remain under diagnosed and undertreated. In 2012, the Spanish Society of Medical Oncology (SEOM) published a clinical practice guideline (CPG) for the treatment of cancer pain which specifically addressed the management of BTcP. Fundación ECO designed a qualitative study using an Internet-based survey to investigate the attitudes toward, compliance with, and use of SEOM Guideline. A total of 83 oncologists with a mean experience of 13 years responded. Overall, 82% were aware of different guidelines to manage BTcP. Notably, attitudes toward guidelines were highly positive and there was nearly unanimous agreement that CPG provided the best scientific evidence available (99%), on the minimum information to be gathered for the medical history (100%), on the need for a specific treatment for BTcP (100%), and fentanyl as the first-choice drug (99%). Interestingly, there were discrepancies between what oncologists agreed with and what they do in clinical practice. In fact, 87.6% declare full compliance with SEOM guideline, although adherence to registration of BTcP data in medical records ranged from 30.1 to 91.6% (mean 64.5%); therapeutic management compliance was higher ranging from 75.9 to 91.6%. Main barriers identified were time pressure together with vague statements and limited dissemination of the guidelines. Despite oncologist's clinical practice is increasingly guided by GPC, it suffers from limited compliance, at least in part due to suboptimal statements. Improved dissemination and education are needed to enhance guideline implementation.


Addressing the critical need for open experimental databases in materials science.
With the HTEM, an open online database containing experimental synthesis and characterization data of thin film inorganic materials, Talley et al. (2021) lay a foundation for a new era of high-throughput materials design.


Short interspersed DNA elements and miRNAs: a novel hidden gene regulation layer in zebrafish?
In this study, we investigated by in silico analysis the possible correlation between microRNAs (miRNAs) and Anamnia V-SINEs (a superfamily of short interspersed nuclear elements), which belong to those retroposon families that have been preserved in vertebrate genomes for millions of years and are actively transcribed because they are embedded in the 3' untranslated region (UTR) of several genes. We report the results of the analysis of the genomic distribution of these mobile elements in zebrafish (Danio rerio) and discuss their involvement in generating miRNA gene loci. The computational study showed that the genes predicted to bear V-SINEs can be targeted by miRNAs with a very high hybridization E-value. Gene ontology analysis indicates that these genes are mainly involved in metabolic, membrane, and cytoplasmic signaling pathways. Nearly all the miRNAs that were predicted to target the V-SINEs of these genes, i.e., miR-338, miR-9, miR-181, miR-724, miR-735, and miR-204, have been validated in similar regulatory roles in mammals. The large number of genes bearing a V-SINE involved in metabolic and cellular processes suggests that V-SINEs may play a role in modulating cell responses to different stimuli and in preserving the metabolic balance during cell proliferation and differentiation. Although they need experimental validation, these preliminary results suggest that in the genome of D. rerio, as in other TE families in vertebrates, the preservation of V-SINE retroposons may also have been favored by their putative role in gene network modulation.


Dipotassium hydrogen phosphate as reducing agent for the efficient reduction of graphene oxide nanosheets.
By using dipotassium hydrogen phosphate (K2HPO4·3H2O), an efficient and environmentally friendly route for the reduction of the exfoliated graphene oxide nanosheets (GO) is reported in this work. The chemically reduced graphene oxide nanosheets (RGO) have been analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectra, X-ray photoelectron spectroscopy, Field emission transmission electron microscopy, Atomic force microscopy, and Thermogravimetric analysis. Considering the analysis results, dipotassium hydrogen phosphate plays a key role in the efficient removal of the oxygen-containing groups in GO, which avoids the use of high toxic and hazardous reducing agents commonly used to obtain RGO in chemical reduction of GO. Dipotassium hydrogen phosphate itself and prepared graphene are environmentally friendly and inexpensive, which may open new opportunities for mass production of graphene by reducing GO.


Formation and growth of the cerebral convolutions. II. Cell death in the gyrus suprasylvius and adjoining sulci in the cat.
Cell death, calculated by counting pyknotic nuclei to assess the number of dying cells, in the gyrus suprasylvius (GS-Syl) and adjoining sulci sulcus lateralis (SL) and sulcus suprasylvius (SS-Syl) was studied in cats aged 5, 15, 25 days and 6 months. Three patterns of cell death were characterized: (1) an ascending gradient from the inner to the upper cortical layers; (2) a lateromedial gradient from the SS-Syl towards the SL; and (3) a predominance of cell death in the sulcal zones. These patterns are in accordance with the sequence of cortical neurogenesis, the lateromedial pattern of the whole formation and growth of the GS-Syl and adjoining sulci, and the differences in the cortical thickness between the sulci and the gyral crown.


A role for dystroglycan in basement membrane assembly.
Basement membranes are composed of ordered arrays of characteristic extracellular matrix proteins, but little is known about the assembly of these structures in vivo. We have investigated the function of dystroglycan, a cell-surface laminin receptor expressed by cells contacting basement membranes in developing and adult tissues. We find that dystroglycan is required for the formation of a basement membrane in embryoid bodies. Our results further indicate that dystroglycanlaminin interactions are prerequisite for the deposition of other basement membrane proteins. Dystroglycan may exert its influence on basement membrane assembly by binding soluble laminin and organizing it on the cell surface. These data establish a role for dystroglycan in the assembly of basement membranes and suggest fundamental mechanisms underlying this process.


Staphylococcus aureus alpha-toxin attack on human platelets promotes assembly of the prothrombinase complex.
alpha-Toxin, the major cytolysin of Staphylococcus aureus, promotes blood coagulation by its attack on human platelets (Bhakdi S., Muhly, M., Mannhardt, U., Hugo, F., Klapettek, K., Mueller-Eckhardt, C., and Roka, L. (1988) J. Exp. Med. 168, 527-542). In the present study we demonstrate that toxin attack on gel-filtered human platelets initiates the assembly of prothrombinase complexes at rates up to 10-fold of controls. Treatment of platelets with 0.1 microgram/ml alpha-toxin resulted in generation of 1.4 units of thrombin/10(8) platelets. A similar rate of thrombin generation was noted when platelets were subjected to three cycles of freezing and thawing. However, the alpha-toxin-induced prothrombinase activity was not due to platelet lysis, since less than 1% of total cellular lactate dehydrogenase was released by this alpha-toxin concentration. Two distinct and dissociable processes contributed to enhanced prothrombinase assembly. First, alpha-toxin promoted the exocytotic release of factor V from alpha-granules, which was accompanied by co-secretion of platelet factor 4. This process was calcium-dependent. Second, toxin-treated platelets exhibited an enhanced capacity to bind external factor V(a), a phenomenon that was not linked to Ca2(+)-dependent factor V secretion. Assembly of prothrombinase complexes via these two mechanisms together accounts for the procoagulant action of S. aureus alpha-toxin.


Energy dependent interaction of oligomycin and dicyclo hexylcarbodiimide with the mitochondrial membrane.
The characteristics of the oligomycin and DCCD inhibitions of energy linked reactions supported by ATP, indicate that the inhibition is increased by the presence of ATP. It is proposed that such an effect can be attributed to an energy linked change in the structure of some component of the ATPase, facilitating oligomycin interaction with the membrane.


Intelligibility of degraded speech and the relationship between symptoms of inattention, hyperactivity/impulsivity and language impairment in children with suspected auditory processing disorder.
To compare the sensitivity and specificity of Auditory Figure Ground sub-tests of the SCAN-3 battery, using signal to noise ratio (SNR) of +8 dB (AFG+8) and 0 dB (AFG0), in identifying auditory processing disorder (APD). A secondary objective was to evaluate any difference in auditory processing (AP) between children with symptoms of inattention versus combined sub-types of Attention Deficit Hyperactivity Disorder (ADHD). Data from 201 children, aged 6 to 16 years (mean: 10 years 6 months, SD: 2 years 8 months), who were assessed for suspected APD were reviewed retrospectively. The outcomes of the SCAN-3 APD test battery, Swanson Nolan and Pelham-IV parental rating (SNAP-IV) and Children's Communication Checklist-2 (CCC-2) were analysed. AFG0 had a sensitivity of 56.3% and specificity of 100% in identifying children performing poorly in at least two of six SCAN-3 sub-tests or one of the two questionnaires, in contrast to 42.1% and 80% respectively for AFG+8. Impaired AP was mostly associated with symptoms of ADHD and /or language impairment (LI). LI was present in 92.9% of children with ADHD symptoms. Children with symptoms of combined ADHD plus LI performed significantly poorly (p < 0.05) compared to inattention ADHD plus LI in Filtered Words (FW) sub-test, but not in the rest of the SCAN-3 sub-tests. Speech in noise tests using SNR of 0 dB is better than +8 dB in assessing APD. The better FW performance of the inattention ADHD plus LI group can be speculated to be related to known difference in activity in a neural network between different sub-types of ADHD. The findings of the study and existing literature suggest that neural networks connecting the cerebral hemispheres, basal ganglia and cerebellum are involved in APD, ADHD and LI.


First molecular detection of porcine circovirus type 3 in dogs in China.
Porcine circovirus type 3 (PCV3) has recently been isolated from diseased pigs within the USA. The objective was to detect the presence of PCV3 in dogs. Nested polymerase chain reactions (PCR) with PCV3-specific primers for the capsid gene were used to detect PCV3 genomic DNA in serum samples from dogs (n = 44) in China. There was PCV3 DNA detected in 4 of 44 dogs [all were negative for PCV2 and canine circovirus (CanineCV)]. Based on sequence analysis, positive sequences were grouped into PCV3 genotypes. However, these isolates had close evolutionary relationships with FoxCV (KP941114) and CanineCV (JQ821392). Further investigations of the epidemiology, evolutionary biology, and pathobiology of PCV3 to dogs are warranted.


A robust zirconium N-heterocyclic carbene complex for the living and highly stereoselective ring-opening polymerization of rac-lactide.
A readily accessible and robust Zr-NHC complex was found to polymerize rac-lactide in a highly controlled, living and stereoselective manner to afford heterotactic PLA.


Thin source spraying method for gross alpha/beta measurements with emphasis on alpha/beta particle self-absorption.
Gross alpha/beta analysis is an initial rapid screening technique used to discriminate alpha- and beta-particle emitters in the nuclear industry. Self-absorption in the sample affects the detection; therefore, self-absorption curves must be constructed. Beta and alpha self-absorption curves were constructed under different conditions. Results reproducibility depends on uniformity of the dry residue on planchets. To determine and compare activities correctly, the preparation method of the sample must be identical to the ones measured the construction of the self-absorption curves.


Epilepsy-related employment prevalence and retirement incidence in the German working population: 1994-2009.
Epilepsy-related employment prevalence and retirement incidence were investigated in the German working population from 1994 to 2009. The overall mean prevalence of employment of people with epilepsy was 5.1±0.2 per 1000 workers. The employment rate among people with epilepsy increased from 63.5% in 1994 to 65.9% in 2000 (0.4% annually) and then more steeply from 66.8% in 2001 to 76.9% in 2009 (1.4% annually). A prominent increase in rate of employment of people with epilepsy since 2001 was temporarily associated with approval of leviteracetam in 2000 (P<0.001, OR=8.3, CI=6.45-10.12). The overall mean employment rate of people with epilepsy was lower than that of the general population (68.5% vs 90.1%, P<0.001). The overall mean incidence of epilepsy-related retirement (RI) during the study was 4.6±1.6/1000, similar to the RI for people with other illnesses (5.1±0.8/1000), and the risk of retiring because of epilepsy was not higher than that for other illnesses over the entire study period (P=0.52, OR=1.11, CI=0.86-1.43). The RI among workers with epilepsy, however, sharply declined from 8.3/1000 in 1994 to 2.9/1000 in 2000 (-65%, < 0.001), followed by a slight increase and stabilization at 3.9/1000 workers between 2001 and 2009. The decline in RI among people with epilepsy was temporarily associated with legislation of the Law on Support of Employment in 1996 (P=0.032, OR=2.15, CI=1.17-2.89) and approval of lamotrigine in 1993 (P=0.024, OR=2.64, CI=2.17-3.88). These patterns suggest that drug treatment and legislative laws may have led to increased employment and reduced retirement rates for people with epilepsy.


Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure. A preliminary investigation.
To determine whether alterations of platelet reactivity occur during obstructive sleep apnea (OSA) and, if so, whether therapy with nasal-continuous positive airway pressure (N-CPAP) alters this reactivity. Patients with suspected moderate to severe OSA had blood drawn for spontaneous platelet aggregation (sAGG) and activation (sACT) measurements at hourly intervals during diagnostic polysomnography (PSG) and, in those with confirmed OSA, on a separate night during which N-CPAP was applied. Tertiary care center sleep laboratory. Six patients with OSA had matched blood samples drawn on both diagnostic and N-CPAP treatment nights. Five patients without confirmed OSA served as controls. N-CPAP was applied to those patients with OSA and pressures adjusted with goals of eliminating apneas; N-CPAP was then maintained through the night. sACT and sAGG were measured using flow cytometric determination of P-selectin expression using a monoclonal antibody. Platelet aggregation was assessed by measuring the proportion of platelets larger than resting platelets by light scatter techniques. Mean values for sACT and sAGG were higher on the diagnostic night compared with treatment night (p = 0.001 and p = 0.003, analysis of variance, respectively). The mean baseline supine sACT compared with completion supine sACT for both diagnostic and N-CPAP nights also revealed significant differences (mean = 16.6 +/- 3.5% vs 36.9 +/- 7.5%, p = 0.04; and 11.9 +/- 3% vs 39.5 +/- 9.1%, p = 0.04). Platelet activation during sleep in five subjects without OSA resembles that found in patients with OSA during N-CPAP. Increased platelet sACT and sAGG occur during sleep in patients with OSA. This effect is greatly reduced by N-CPAP.


Lateral mobility of human erythrocyte integral membrane proteins.
Fluorescein isothiocyanate-labelled integral membrane proteins are mobile in the membranes of human erythrocytes that have fused (and haemolysed) by Sendai virus or polyethylene glycol. Minimum diffusion coefficients are of the order of 10(-11) cm2 s-1 at 37 degrees C. This mobility is reduced several-fold at room temperature, not detected at 0 degrees C, and is significantly greater in fresh than in aged blood. Mobility was assessed by observing the spread of fluorescence on labelled cells which had been fused with unlabelled cells; neither intramembrane particle aggregation nor spectrin release occurred during this process.


Cytotoxic T cells react with recombinant Yo protein from a patient with paraneoplastic cerebellar degeneration and anti-Yo antibody.
Antibodies against autologous tumor cells and neurons are found in the sera or cerebrospinal fluid of patients with paraneoplastic neurological syndromes. Attempts to produce animal models by passive transfer or active immunization, however, have failed, and there is no direct evidence that antibodies cause neuronal damage. Previously, we found that patients with paraneoplastic cerebellar degeneration (PCD) and anti-Yo antibody tested had HLA A24. We now have studied cytotoxic T cell activity in peripheral blood that reacts with recombinant Yo protein when autologous dendritic cells are used as the target. Results suggest that cytotoxic T cells are involved in Purkinje cell loss in PCD.


Effects of temperature shift on cell cycle, apoptosis and nucleotide pools in CHO cell batch cultues.
Temperature reduction in CHO cell batch culture may be beneficial in the production of recombinant protein and in maintenance of viability. The effects on cell cycle, apoptosis and nucleotide pools were studied in cultures initiated at 37°C and temperature shifted to 30 °C after 48 hours. In control cultures maintained at 37 °C, viable cells continued to proliferate until the termination of the culture, however, temperature reduction caused a rapid decrease in the percent of cells in S phase and accumulation of cells in G-1. This was accompanied by a concurrent reduction in U ratio (UTO/UDP-GNAc), previously shown to be a sensitive indicator of growth rate. Culture viability was extended following temperature shift, as a result of delayed onset of apoptosis, however, once initiated, the rate and manner of cell death was similar to that observed at 37 °C. All nucleotide pools were similarly degraded at the time of apoptotic cell death. Temperature reduction to 30 °C did not decrease the energy charge of the cells, however, the overall rate of metabolism was reduced. The latter may be sufficient to extend culture viability via a reduction in toxic metabolites and/or limitation of nutrient deprivation. However, the possibility remains that the benefits of temperature reduction in terms of both viability and productivity are more directly associated with cultures spending extended time in G-1.


Reclassifying formerly indeterminate thyroid FNAs using the Bethesda system reduces the number of inconclusive cases.
To evaluate the effectiveness of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) and to analyze the causes of unclear diagnoses following BSRTC adoption. According to the BSRTC, we reclassified cytologic samples originally diagnosed as 'indeterminate' with sequential surgical resection. Then, we analyzed the causes of cases, which were recategorized as 'atypia undetermined significance/follicular lesion of undetermined significance (AUS/FLUS)'. According to the BSRTC, 154 'indeterminate' cases were reclassified as follows: unsatisfactory, n = 5 (3.2%); benign, n = 43 (27.9%); AUS/FLUS, n = 77 (50.0%); suspicious for a follicular neoplasm, n = 7 (7.1%); suspicious for a Hürthle cell neoplasm, n = 4 (2.6%); suspicious for malignancy, n = 15 (9.7%), and malignancy, n = 3 (1.9%). Then, the AUS/FLUS group was analyzed according to the scenarios proposed by the BSRTC. Fifty-nine (58.9%) cases of AUS/FLUS were due to suboptimal preparation. In addition, papillary microcarcinoma and coexisting Hashimoto's thyroiditis caused inconclusive diagnoses. The BSRTC can be easily applied to thyroid fine-needle aspiration. We were able to reclassify indeterminate thyroid nodules into more detailed categories and thus reduce the number of cases classified as indeterminate. However, suboptimal preparation, papillary microcarcinoma, and coexisting Hashimoto's thyroiditis precluded cytopathologists from making definitive diagnoses.


Lagged effects of active coping within the demand-control model: a three-wave panel study among Japanese employees.
There have been few empirical studies to explain the individual differences in and the underlying mechanism behind the Job Demand-Control (DC) Model. This study examined the lagged effects of active coping on stress responses (i.e., psychological distress and physical complaints) in the context of the DC Model using three-wave panel survey data with intervals of one month. Participants were 193 employees working in a construction machinery company in Japan. Hierarchical multiple regression analyses were conducted to examine whether or not the effectiveness of active coping would be facilitated by job control as a coping resource. The advantage of job control in combination with active coping became obvious after one month, which implies that job control has a delayed effect on coping effectiveness. However, the advantage disappeared after two months. These results suggest that the advantage of job control for active coping is limited in time. Conceptualization of job control as a coping resource seems to be useful in explaining how the DC Model influences employees' health, where time plays an important role.


Influence of thalamic cooling on sensory responses in association cortex.
Evoked responses to light flash, click, and paw stimuli were recorded in the four cortical association areas in the acutely prepared cat. Average evoked responses (AEP) for 100 trials were formed before, during, and after localized cooling in the midline thalamus. Cooling of the midline thalamus reduced the magnitude of responses to click and paw stimuli, and increased or did not change the responses to light flash. There was very little similarity in trial-to-trial fluctuations of EP magnitude across cortical areas, and cooling did not reduce the similarity that existed. Waveform similarity was reduced by cooling for responses across the cortex to a single stimulus modality, whereas similarity of responses in a single cortical area to all three stimuli was not changed. The temporal components of the AEP influenced by thalamic cooling were different for different stimuli and cortical locations. It was concluded that the midline thalamo-cortical projection through the centromedian area to association cortices is particularly well-differentiated for multisensory responses in a single cortical region, and that the system should not be thought of as nonspecific but as convergent or multisensory.


Stomal obstruction of ileal conduits in children: a urodynamic study.
In an attempt to diagnose stomal obstruction before radiological evidence is present, urodynamic perfusion studies were done on 40 children with ileal conduit diversion. Residual urine, capacity, resting pressure and mean emptying pressure were recorded after perfusion of the conduit with normal saline at 10 ml. per minute. Emptying pressure appeared to be the most sensitive parameter of obstruction. Residual urine may be normal in early obstruction and may be increased in the presence of normal emptying pressures in atonic conduits.


Status Epilepticus: A Neurologic Emergency.
In this review, we discuss treatment and considerations for status epilepticus in general intensive care unit patients, acquired brain injury, autoimmune conditions, toxidromes, pediatrics, and pregnancy.


[Spanish cardiac catheterization and coronary intervention registry. 20th official report of the spanish society of cardiology working group on cardiac catheterization and interventional cardiology (1990-2010)].
The Working Group on Cardiac Catheterization and Interventional Cardiology presents on a yearly basis a report on the data collected for the national registry. This information displays how procedures are distributed throughout Spain and makes comparisons with other countries feasible. Institutions render their data voluntarily (online) and they are analyzed by the Working Group's steering committee. Data was sent by 113 hospitals (71 public and 41 private) that treat mainly adults, reporting 135 486 diagnostic procedures, 119 118 of them coronary angiograms, slightly less than the year before, and with a rate of 2945 coronary angiograms per million inhabitants. Percutaneous coronary interventions increased a bit, to 64331 procedures and a rate of 1398 interventions per million. Of 100371 stents implanted, 61.3% were drug-eluting stents. In the acute phase of myocardial infarction, 14248 coronary interventions were carried out, 6% more than in 2009 and 22% of the total number of coronary interventions. The most frequent intervention for adult congenital heart disease was closure of an atrial septal defect (295 procedures). Percutaneous mitral valvuloplasty continues to decrease (326 procedures) and percutaneous aortic valve implantations are growing rapidly, with 655 units implanted in 2010. The greatest increase in activity has occurred in the field of myocardial infarction and percutaneous aortic valve implantation. The other procedures, both diagnostic and therapeutic, remain stable.


Calculation of O2 saturation and of the oxyhemoglobin dissociation curve for different species, using a new programmable pocket calculator.
The degree of O2 saturation and different data of acid-base status are determined from pO2, pH, and pCO2 values bya programmable pocket calculator. Since the operating program should be usable for different species and also in the range of very low O2 saturations, obviously the usual Hill equation for calculating the oxygen dissociation curve of hemoglobin is not applicable; the same is true is some cases for the Adair equation. Thus a 3-fold subdivision of the dissociation curve was undertaken and programmed. Suitable programs for several species could be established despite the limited number of program steps in the new calculator, giving systematic deviations in calculated O2 saturations of less than or equal to +/- 0.9 saturation precent over the full range of dissociation curves. A reverse procedure for calculation of pO2 from saturation is added. In situations where pCO2 or base excess are not known or only estimated, limits of the arising error are stated. In the acid-base program 7 parameters are evaluated partially using empirical formulae derived from nomograms. The programmable pocket calculator offers advantages of small size, economy, and independence of line voltage compared to much more spacious units and a precision equal or superior to nomograms.


Should we change our lipid management strategies to focus on non-high-density lipoprotein cholesterol?
Despite aggressive low-density lipoprotein cholesterol lowering, patients continue to be at significant risk of cardiovascular events. Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the third Adult Treatment Panel guidelines, non-HDL-C was introduced as a secondary target of therapy. A combined post-hoc analysis of data from two prospective, randomized trials assessing the role of statins in patients with established coronary heart disease showed that on-treatment levels of non-HDL-C were more closely associated with cardiovascular outcomes than levels of low-density lipoprotein cholesterol. A recent meta-analysis of the relationship between non-HDL-C reduction and coronary heart disease risk showed that most lipid-modifying drugs used as monotherapy have a 1 : 1 relationship between percentage non-HDL-C lowering and percentage coronary heart disease reduction. In the European Prospective Investigation Into Cancer and Nutrition-Norfolk prospective population study (n = 21,448), participants with high non-HDL-C levels were at increased coronary heart disease risk independently of their low-density lipoprotein cholesterol levels. Because non-HDL-C appears to be superior for risk prediction beyond low-density lipoprotein cholesterol, future guidelines should emphasize the importance of non-HDL-C for guiding cardiovascular prevention strategies. There is an increased need to have non-HDL-C reported on routine lipid panels, especially because it would be at no added cost.


Effects of gonadotropins, 11-ketotestosterone, and insulin-like growth factor-1 on target gene expression and growth of previtellogenic oocytes from shortfinned eels, Anguilla australis, in vitro.
Pituitary gonadotropins, metabolic hormones, and sex steroids are known factors affecting the advanced stages of ovarian development in teleost fish. However, the effects of these hormones and of the interactions between them on the growth of previtellogenic ovarian follicles are not known. In order to address this void in understanding, previtellogenic ovarian fragments from eel, Anguilla australis, were incubated in vitro with recombinant Japanese eel follicle-stimulating hormone (rec-Fsh), human chorionic gonadotropin (hCG), or 11-ketotestosterone (11-KT) in the presence or absence of recombinant human insulin-like growth factor-1 (IGF1). The results of long-term in vitro culture (21 days) demonstrated that rec-Fsh and 11-KT, rather than hCG, caused significant increases in the diameter of previtellogenic oocytes. Meanwhile, only 11-KT induced a significant increase in lipid accumulation. Moreover, a greater effect on oocyte growth was observed when IGF1 supplementation was combined with 11-KT rather than with rec-Fsh or hCG. For short-term culture (24 h), treatment with 11-KT in the presence or absence of IGF1 had no significant effects on mRNA levels of target genes (lhr, cyp19, cyp11b, lpl, and ldr) except for upregulation of fshr. There were no significant effects of rec-Fsh on expression of any target gene, whereas hCG downregulated the expression of these genes. There was no evidence for any interaction between the gonadotropins and IGF1 that resulted in growth of previtellogenic oocytes. Taken together, these results suggest that hormones from both the reproductive and the metabolic axes regulate the growth of previtellogenic oocytes in Anguilla australis.


E-cigarette use and asthma in a multiethnic sample of adolescents.
There is minimal evidence from epidemiological studies on how e-cigarette use is related to health indices in adolescence. We hypothesized that e-cigarette use would be associated with asthma, controlling for demographics and cigarette smoking. The hypothesis was tested with cross-sectional data from a statewide sample of school students. Surveys were administered in classrooms in 2015 to adolescents in 33 high schools throughout the State of Hawaii. The sample (N=6089) was 50% female and mean age was 15.8years. Data were obtained on demographics; ever use and current (past 30days) use of e-cigarettes, combustible cigarettes, and marijuana; ever being diagnosed with asthma; and currently having asthma. Multinomial regression examined the association between e-cigarette use and asthma controlling for cigarette smoking, marijuana use, and six demographic covariates. Current e-cigarette use was associated with currently having (vs. never having) asthma (adjusted odds ratio [aOR]=1.48, CI 1.26-1.74) and with previously having (vs. never having) asthma (aOR=1.22, CI 1.07-1.40). This was independent of cigarette smoking, marijuana use, and other covariates. Smoking and marijuana were nonsignificant in the multivariate analysis. Blacks, Native Hawaiians, other Pacific Islanders, and Filipinos had higher rates of asthma compared with Asian Americans and Caucasians. We conclude that e-cigarette use by adolescents is independently associated with asthma. This finding is consistent with recent laboratory research on pulmonary effects from e-cigarette vapor. Implications for public health should be considered.


The properties of poly(lactic acid)/starch blends with a functionalized plant oil: tung oil anhydride.
Bio-sourced polymers, polylactide (PLA) and starch, have been melt-blended by lab-scale co-extruder with tung oil anhydride (TOA) as the plasticizer. The ready reaction between the maleic anhydride on TOA and the hydroxyl on starch led TOA molecules to accumulate on starch and increased the compatibility of PLA/starch blends, which was confirmed by FT-IR analyses and SEM. The TOA could change the mechanical properties and physical behaviors of PLA/starch blends. DSC and DMA analysis show that the TOA layer on starch has an effect on the thermal behavior of PLA in the ternary blend. The enrichment of TOA on starch improves the toughness and impact strength of the PLA/starch blends. The adding amount of TOA in PLA/starch blends primarily determined the compatibility and mechanical properties of the resulted ternary blends. The tensile and impact fracture modes of the PLA/starch blend with or without TOA has also been investigated by SEM analysis.


Alterations of the default mode network in functional dyspepsia patients: a resting-state fmri study.
Increasing brain imaging studies have emphasized the role of regional brain activity abnormalities in functional dyspepsia (FD) during the resting state. The goal of this study was to investigate the default mode network (DMN) in FD patients and healthy controls (HCs). Resting-state functional magnetic resonance imaging (fMRI) scanning was carried out on 49 patients and 39 HCs. Independent component analysis (ICA) was used to isolate the DMN in each subject. Group topography of the DMN was compared to study significant alteration in FD. A correlation analysis was then performed in the FD group to investigate the effects of symptom severity and the psychological factors on the DMN. Significant spatial differences with the DMN in FD patients, compared with HCs, were mainly found in the dorsomedial prefrontal cortex (dmPFC), ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex (OFC), pregenual anterior cingulate cortex (pACC), thalamus, parahippocampal gyrus, precuneus, parietal cortex, and temporal pole. Meanwhile, Nepean Dyspepsia Index (NDI) scores were positively correlated with the pACC, and was negative correlated with the OFC. However, both the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores were not correlated with any regions of interest showing differences between the FD patients and the HCs. These findings suggested that the DMN might indeed undergo dysfunctional changes due to the abnormal persistent activity in FD patients. To a certain extent, the changes in the DMN were related to the FD-related symptom severity.


Vocal Evaluation of Children with Congenital Hypothyroidism.
To evaluate the vocal characteristics of a group of children with congenital hypothyroidism (CH) and the association of these characteristics with the children's clinical, laboratory, and therapeutic profiles. Observational, analytical, cross-sectional study including 200 prepubertal children, of whom 100 had CH (study group [SG]) and 100 had no CH (control group [CG]). The following parameters were evaluated: 1) history (identification, complaints, and interfering variables), 2) auditory-perceptual and acoustic evaluation (samples analyzed by a group of specialists, and objectively by a computer program), 3) self-assessment scores in the Pediatric Voice-Related Quality-of-Life (PVRQoL) survey, 4) laryngological evaluation (presence or absence of laryngeal lesions and data regarding glottal closure), and 5) medical records (CH etiology, age at treatment initiation, disease severity at diagnosis, treatment quality, and thyroid function tests on the day of the examination). In the perceptual assessment, 62.6% of the SG children passed, whereas 37.4% failed in the voice screening, but these results were comparable with those in the CG (P = 0.45). Both groups had mean/median acoustic measurements within the normal limits. The mean PVRQoL in the SG (99.3 ± 2.4) and CG (99.5 ± 1.7) were comparable (P = 1.00). Both SG (16.7%) and CG (15%) presented vocal cord lesions (P = 1.00). There was no association between voice/larynx characteristics and endocrinological data. Prepubescent children diagnosed with CH during neonatal screening and who have a lifelong history of adequate treatment of CH showed similar vocal and laryngeal characteristics compared with children without CH.


Interactions of mycorrhizal fungi with Pteris vittata (As hyperaccumulator) in As-contaminated soils.
A greenhouse trial was conducted to investigate the role of arbuscular mycorrhizas (AM) in aiding arsenic (As) uptake and tolerance by Pteris vittata (As hyperaccumulator) and Cynodon dactylon (a multi-metal root accumulator). Plants inoculated with lived and killed native mycorrhizas isolated from an As mine site were grown in a sterile and slightly acidic soil. The infectious percentage of mycorrhizas (0 mg/kg As: 26.4%, 50 mg/kg As: 30.3%, 100 mg/kg As: 40.6%) and the average biomass of shoots in infected P. vittata increased (0 mg/kg As: 2.45 g/pot, 50 mg/kg As: 2.48 g/pot, 100 mg/kg As: 10.9 g/pot) according to the increase of As levels when compared to control. The indigenous mycorrhizas enhanced As accumulation (0 mg/kg As: 3.70 mg/kg, 50 mg/kg As: 58.3 mg/kg; 100 mg/kg As: 88.1 mg/kg) in the As mine populations of P. vittata and also sustained its growth by aiding P absorption. For C. dactylon, As was mainly accumulated in mycorrhizal roots and translocation to shoots was inhibited.


Molecular properties of glutamate dehydrogenase from the extreme thermophilic archaebacterium Sulfolobus solfataricus.
This study is concerned with the structural characterization in solution of the glutamate dehydrogenase from the Archaeon Sulfolobus solfataricus. At neutral pH both alpha-helix and beta-sheet constitute the secondary structure of this enzyme, on the basis of circular dichroism. A complex, temperature dependent self-association equilibrium regulates the formation of the enzyme quaternary structure, which seems to be accompanied by a reversible structural change. At 25 degrees C the enzyme is mostly represented by monomeric subunits at concentrations lower than 0.02 mg/ml, while oligomers are predominant at concentrations higher than 0.12 mg/ml. The mid-point of the association curve shifts from 0.05 mg/ml at 25 degrees C to about 0.1 mg/ml at 45 degrees C. Only the oligomeric form appears to be temperature resistant. Monomeric and oligomeric enzyme show distinct behaviour on guanidine hydrochloride perturbation at neutral pH. The monomer denaturation, although complex, is reversible. Two fluorescent tryptophan classes are detectable in the monomer, monitoring the independent unfolding of two regions through a multistate transition. Instead, the oligomeric protein shows a complex denaturation pattern with the tendency to aggregate irreversibly at high denaturant concentration.


Orbital emphysema following remote skull trauma.
In an unusual case of orbital emphysema following nose blowing, a reliable patient history and examination demonstrated no direct trauma to the orbit. Blunt posterior skull trauma was sustained several hours before the development of the orbital emphysema. A "seismic" transmittal of force to the orbital walls is postulated.


The differentiation of early embryonic stem cells into adipocytes-like cells.
An early embryonic stem cell line, EES-6 cells, was established from 2-cell stage embryos of ddY mice. The cells were maintained in an undifferentiated state with D-MEM/F12 medium supplemented with 10% fetal bovine serum (FBS) (GM) and 1 ng of leukemia inhibitory factor (LIF) without any feeder cells. In this study, EES cells were cultured with a medium containing embryotrophic factors (ETFs) which promoted the differentiation of EES cells into white and brown adipocytes-like cells for a period of 5 days. Lipid droplets in brown adipocyte-like cells were stained with Sudan III; however, large lipid-like droplets in white or brown adipocyte-like cells were unstained with either Sudan III or alcian blue. These findings have numerous possibilities for therapeutic use such as regeneration of skin and wound healing.


Does the noncompetitive NMDA receptor antagonist dizocilpine (MK801) really block behavioural sensitization associated with repeated drug administration? .
The term 'behavioural sensitization' refers to the progressively augmented behavioural response that is produced by many drugs of abuse upon their repeated administration. From most of the available data, it has been concluded that co-administration of an N-methyl-D-aspartate (NMDA) receptor antagonist [such as dizocilpine (MK801)] together with the sensitizing drug can block the development of behavioural sensitization. However, the picture might not be that simple. Recent experimental evidence suggests that instead of blocking sensitization, co-administration of dizocilpine enhances the effect of the the sensitizing drug or has more complex effects on the development of sensitization. In this article, Thomas Tzschentke and Werner Schmidt present these two different views and emphasize that the conclusions that can be drawn from sensitization experiments about the effects of dizocilpine and related drugs on behavioural plasticity crucially depend on how, when and under what conditions a test for sensitization is conducted.


Picrorhiza kurroa, Royle ex Benth:Traditional uses, phytopharmacology, and translational potential in therapy of fatty liver disease.
Picrorhiza kurroa Royle ex Benth, Kutki (P.kurroa) is an important medicinal plant, traditionally recommended and used in Ayurveda for millennia, with certain cautions. There has been a significant revival of keen interest in its pharmacology, pharmacognosy, and phytochemistry for the last few decades. The evidence of its hepatoprotective activity, in experimental and clinical studies, accelerated the correlation of the specific phytochemical constituents of P.kurroa with precise pharmacological activities. Iridoid glycosides, particularly picrosides, emerged as the active molecules. For effective translation of traditional remedies into modern therapy, value addition by mechanistic understanding of molecular actions, drug targets, the degrees of efficacy and safety as well as convenient dosage forms is needed. Reverse pharmacology approach and phytopharmaceutical drug category facilitate such a translation. The present review illustrates how a potential translation of traditional practices of using P.kurroa into a phytochemically standardized, clinically targeted natural product for global unmet medical needs viz. Fatty liver disease can be attained.


Molecular characterization and detection of a new closterovirus identified from blackcurrant by high-throughput sequencing.
Two large contigs with high sequence similarities to several closteroviruses were identified by high-throughput sequencing from a blackcurrant plant. The complete genome of this new virus was determined to be 17,320 nucleotides. Its genome contains ten open reading frames (ORF) that include, in the 5'-3' direction, a large ORF encoding a putative viral polyprotein (ORF 1a) and nine ORFs that encode RNA-dependent RNA polymerase (RdRp, ORF 1b), p6 (ORF 2), heat shock protein 70-like protein (Hsp70h, ORF 3), Hsp-90-like protein (p61, ORF 4), CP minor (ORF 5), CP (ORF 6), p17 (ORF 7), p11 (ORF 8), and p26 (ORF 9), respectively. BCCV-1 shares nucleotide sequence identities of 43-45% with other 9 closteroviruses at genome sequences. The amino acid sequence identities between BCCV-1 and the closteroviruses were 49-55% (RdRp), 37-41% (Hsp70h), 19-33% (p61), 26-38% (CPm), and 19-28% (CP), respectively. Phylogenetic analysis of Hsp70h sequences placed the new virus with members of genus Closterovirus in the same group. The results indicate that this new virus, which is provisionally named as Blackcurrant closterovirus 1, should represent a new species of the genus Closterovirus. A RT-PCR was developed and used to detect BCCV-1 in more germplasm accessions of Ribes spp.


Cytogenetic and molecular analysis of the pufferfish Tetraodon fluviatilis (Osteichthyes).
In view of their compact genome, pufferfish (Tetraodontiformes) have been proposed as model animal for the study of the vertebrate genome. Despite such interest, cytogenetic information about puffers is still scanty. To fill this gap, a cytogenetic analysis of T. fluviatilis has been performed using both classical and molecular techniques. C-banding, followed by DAPI staining, evidenced that in T. fluviatilis, like all other puffer species so far examined, heterochromatin is essentially AT-rich and it is located at centromeres, whereas staining with CMA3, silver staining and FISH with a 28S ribosomal RNA gene DNA probe showed 2-4 nucleolar organizing regions (NORs) located in heterochromatic regions in the considered puffer species. FISH with the 5S probe put in evidence both in T. fluviatilis and in T. nigroviridis only a 5S cluster per haploid genome that is physically unlinked with the major ribosomal RNA genes including the 28S rRNA genes. Hybridization with the (TTAGGG)n probe showed in all the puffers brightly fluorescent signals uniform both in size and intensity at the end of all the chromosomes. Finally, mariner-like elements (MLEs) have been identified in T. fluviatilis and they have located into the NOR-associated heterochromatin.


Changes in health-related quality of life with intensive behavioural therapy combined with liraglutide 3.0 mg per day.
This study examined the effects of intensive behavioural therapy (IBT) for obesity (IBT-alone), IBT plus liraglutide 3.0 mg/day (IBT-liraglutide), and IBT-liraglutide combined with 12 weeks of a portion-controlled diet (Multicomponent) on changes in general health-related (HR) quality of life (QoL) and weight-related QoL. Adults with obesity (79.3% female; 54.0% white; 44.7% black; mean age = 47.6 ± 11.8 years and body mass index = 38.4 ± 4.9 kg/m2 ) were randomized to IBT-alone (n = 50), IBT-liraglutide (n = 50) or Multicomponent (n = 50). General HRQoL was measured with the Short Form-36 (SF-36), and weight-related QoL was assessed with the Impact of Weight on Quality of Life-Lite scale. At week 52, participants in the three groups lost 6.1 ± 1.3%, 11.5 ± 1.3% and 11.8 ± 1.3% of initial body weight, respectively. Both liraglutide-treated groups were significantly more likely than IBT-alone to achieve clinically meaningful improvements in total weight-related QoL. They also both achieved greater improvements than IBT-alone in weight-related public distress and in general mental health, as measured by the SF-36 mental component summary score. Independent of treatment group, greater categorical weight loss was associated with greater improvements in several domains of both general and weight-related QoL. The addition of liraglutide to IBT appeared to improve aspects of both general HRQoL and weight-related QoL.


The pharmacology of second-generation chimeric antigen receptors.
Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.


Impact of climate change on drought in Aragon (NE Spain).
Droughts are one of the extreme climatic phenomena with the greatest and most persistent impact on health, economic activities and ecosystems and are poorly understood due to their complexity. The exacerbation of global warming throughout this century probably will cause an increase in droughts, so accurate studies of future projections at a local level, not done so far, are essential. Climate change scenarios of drought indexes for the region of Aragon (Spain) based on nine Earth System Models (ESMs) and two Representative Concentration Pathways (RCPs) corresponding to the fifth phase of the Coupled Model Intercomparison Project (CMIP5) have been generated for the first time. Meteorological Drought episodes were analysed from three main aspects: magnitude (index values), duration and spatial extent. The evolution of drought is also represented in a novel way, allowing identification, simultaneously, of the intensity of the episodes as well as their duration in different periods of accumulation and, for the first time, at the observatory level. Future meteorological drought scenarios based on the Standardized Precipitation Index (SPI) hardly show variations in water balance with respect to normal values. However, the Standardized Precipitation Evapotranspiration Index (SPEI) which, in addition to precipitation, considers evapotranspiration, shows a clear trend towards increasingly intense periods of drought, especially when considering cumulative periods and those at the end of the century. Representation of the territory of the drought indexes reflects that the most populated areas (Ebro Valley and SW of the region), will suffer the longest and most intense drought episodes. These results are key in the development of specific measures for adapting to climate change.


Corrigendum: BI 1015550 is a PDE4B inhibitor and a clinical drug candidate for the oral treatment of idiopathic pulmonary fibrosis.
[This corrects the article DOI: 10.3389/fphar.2022.838449.].


Methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate-cyclohydrolase-formyltetrahy dro folate synthetase. Affinity labelling of the dehydrogenase-cyclohydrolase active site.
Methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase are inactivated in parallel by carbodiimide-activated folic acid in an NADP-dependent reaction. Modification with tritium-labelled reagent resulted in the incorporation of 1 mole 3H-folate per mole polypeptide, which demonstrates that these activities share a single folate binding site.


Stem cells in treatment of crohn's disease: Recent advances and future directions.
Crohn's disease (CD) is an inflammatory bowel disease that can affect any part of the intestine. There is currently no recognized cure for CD because its cause is unknown. One of the modern approaches that have been suggested for the treatment of CD and other inflammatory-based disorders is cell therapy. Search terms were stem cell therapy, CD, adipose-derived stem cells, mesenchymal stem cells, and fistula. Of 302 related studies, we removed duplicate and irrelevant papers and identified the ones with proper information related to our scope of the research by reviewing all the abstracts and categorizing each study into the proper section. Nowadays, stem cell therapy is widely implied in treating CD. Although mesenchymal and adipose-derived tissue stem cells proved to be safe in treating Crohn's-associated fistula, there are still debates on an optimal protocol to use. Additionally, there is still a lack of evidence on the efficacy of stem cell therapy for intestinal involvement of CD. Future investigations should focus on preparing a standard protocol as well as luminal stem cell therapy in patients.


Rural and Remote Food Environments and Obesity.
Within most developed countries, rural residents are more likely to be obese and overweight compared to their urban counterparts. Studies of specific rural communities have found that the limited availability of healthy foods in the community and home as well as individual characteristics and preferences contribute to poor diet and overweight. The rural food environment is varied and may be affected by climate, regional and cultural preferences, transportation access, and remoteness among other factors. Given this diversity and the vulnerabilities of rural residents, who are more likely to have low-income, substandard housing or low educational attainment compared to their urban counterparts, policy and programmatic interventions should target specific needs and communities. This review will describe the rural community, home, and individual food environments and what is known about their roles in healthy eating.


Structural functional and folding scenario of an anti platelet and thrombolytic enzyme crinumin.
A folding pattern, conformational stability and therapeutic role of a protein helps in developing a suitable drug. Crinumin, a thrombolytic and anti platelet agent, has been studied for its functional and conformational properties by equilibrium unfolding methods. The crinumin belongs to α+β class of protein and exhibits a non native structure and two molten globule states at different conditions. Two domains in the molecular structure of the protein with altered stability are present that unfold sequentially. The enzyme maintains activity as well as structural integrity even in adverse conditions. These observations provide an understanding of protein folding as well as facilitate the development of a potential drug.


Crystal and mol-ecular structure of 4-fluoro-1H-pyrazole at 150 K.
Only two 4-halo-1H-pyrazole crystal structures are known to date (chloro and bromo, the structure of 4-iodo-1H-pyrazole has not been reported yet). The triclinic structure of 4-fluoro-1H-pyrazole, C3H3FN2 (P ), reported here is not isomorphous with those of the chloro and bromo analogues (which are isomorphous, ortho-rhom-bic Pnma). To avoid sublimation during the measurement, diffraction data were collected at 150 K. Two crystallographically unique 4-fluoro-1H-pyrazole moieties linked by an N-H⋯N hydrogen bond are found in the asymmetric unit. Unlike the trimeric supra-molecular motifs found in the structures of the chloro and bromo analogues, 4-fluoro-1H-pyrazole forms one-dimensional chains by inter-molecular hydrogen bonding in the crystal.


Recent progress in micro/nano biosensors for shellfish toxin detection.
Shellfish toxins, as one kind of marine toxin, have attracted worldwide attention due to their severe threat to food safety and human health. Therefore, it is highly essential and urgent to develop a low-cost and convenient method to detect these toxins. With the rapid advance in microfabrication processes, micro/nano biosensors provide novel approaches to address this issue. In addition to their features of low cost, portability, easy operation, high efficiency and high bioactivity, micro/nano biosensors have great potential to realize on-the-spot, rapid detection of shellfish toxins. This review focuses on the most recent advances in the development of micro/nano biosensors for shellfish toxin detection. These biosensors are mainly classified into five categories according to their transducer detection principles, which include optical devices, electrochemical sensors, electrochemiluminescence, field-effect transistors, and acoustic devices. Sensor strategies, toxin analytes, biosensitive elements, coupling methods and field detection performance are highlighted to discuss the applications of shellfish toxin detection. With advances in sensor technology, biomaterials, microfabrication and miniaturized electronics, micro/nano biosensors applied to in-field fast detection of shellfish toxins are expected to play a critical role in food safety, environmental monitoring, and foreign trade in the foreseeable future. Finally, the current challenges and future development trends of micro/nano biosensors for shellfish toxin detection are discussed.


Development of a POCT type insulin sensor employing anti-insulin single chain variable fragment based on faradaic electrochemical impedance spectroscopy under single frequency measurement.
To improve glycemic control managed through insulin administration, recent studies have focused on developing hand-held point-of-care testing (POCT) electrochemical biosensors for insulin measurement. Amongst them, anti-insulin IgG-based sensors show promise in detecting insulin with high specificity and sensitivity. However, fabrication of electrochemical sensors with IgG antibodies can prove challenging because of their larger molecular size. To overcome these limitations, this study focuses on utilizing the anti-insulin single chain variable fragment (scFv) as a biosensing molecule with single-frequency faradaic electrochemical impedance spectroscopy (EIS). By comparing two different immobilization methods, covalent conjugation via succinimidyl ester and non-covalent poly-histidine chelation, we demonstrated effective modification of the electrode surface with anti-insulin scFv, while retaining its specific recognition toward insulin. Sensor performance was confirmed via the concentration-dependent faradaic electrochemical impedance change using potassium ferricyanide as a redox probe. The optimal frequency for measurement was determined to be the peak slope of the calculated impedance correlation with respect to frequency. Based on the identified optimized frequency, we performed single-frequency measurement of insulin within a concentration range of 10 pM-100 nM. This study can aid in developing a future point-of-care sensor which rapidly and sensitively measures insulin across a dynamic range of physiological concentrations, with label-free detection.


Relationships among blood pressure, triglycerides and verbal learning in African Americans.
Individuals at greater risk for cardiovascular disease (CVD) display poorer cognitive functioning across various cognitive domains. This finding is particularly prevalent among older adults; however, few studies examine these relationships among younger adults or among African Americans. The objective was to examine the relationships among 2 cardiovascular risk factors, elevated blood pressure and elevated triglycerides, and verbal learning in a community-based sample of African Americans. Measurements of blood pressure and triglycerides were obtained in 121 African-American adults and compared to performance on 3 domains of the California Verbal Learning Test-II (CVLT-II). Blood pressure was not related to CVLT-II performance. Triglyceride levels were inversely related to CVLT-II performance. Higher triglyceride levels were associated with poorer immediate, short delay and long delay recall. Consistent with studies involving older participants, the current investigation shows that in a nonelderly sample of African Americans, triglyceride levels may be related to cognitive functioning. Because early detection and intervention of vascular-related cognitive impairment may have a salutary effect, future studies should include younger adults to highlight the impact of cardiovascular risk on cognition.


Histological analysis of bone/heteroplastic implant interfaces in dog tibia.
This work presents histological analysis of interfaces between bone and heteroplastic implants in dog tibias. The study was performed in four tibias (of four mongrel dogs) into which cylindrical implants were inserted. One ceramic (titania) implant and three grit-blasted titanium implants (with sandblasted and acid-corroded surfaces) were chosen for histological analysis of the implant surface/bone tissue interface. The implants remained in the tibias for eight months and none were loaded during this period. The animals were subsequently sacrificed and the samples were processed for analysis. Light microscope analysis revealed a large amount of osteoid tissue and proximity of osteoblasts and osteocytes to the implant surfaces. In addition, little or no fibrous tissue was observed between the bone and implant surfaces. The titanium implants presented better osseointegration than did the ceramic implant.


Incidence of Early Atrial Fibrillation After Transcatheter versus Surgical Aortic Valve Replacement: A Meta-Analysis of Randomized Controlled Trials.
Post-operative atrial fibrillation (POAF) is common after aortic valve replacement (AVR) and is associated with worse outcomes. We performed a meta-analysis of randomized controlled trials comparing Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) for incidence of POAF at 30 days. We searched databases from 1/1/1990 to 1/1/2020 for randomized studies comparing TAVR and SAVR. POAF was defined as either worsening or new-onset atrial fibrillation. Random effects model was used to estimate the risk of POAF with TAVR vs SAVR in all trials, and in subgroups (low, intermediate, high risk, and in self-expandable vs balloon expandable valves). Sensitivity analysis was performed including only studies reporting new-onset atrial fibrillation. Seven RCTs were identified that enrolled 7,934 patients (3,999 to TAVR and 3,935 to SAVR). The overall incidence of POAF was 9.7% after TAVR and 33.3% after SAVR. TAVR was associated with a lower risk of POAF compared with SAVR (OR 0.21 [0.18-0.24]; P < 0.0001). Compared with SAVR, TAVR was associated with a significantly lower risk of POAF in the high-risk cohort (OR 0.37 [0.27-0.49]; P < 0.0001), in the intermediate-risk cohort (OR 0.23 [0.19-0.28]; P < 0.0001), low-risk cohort (OR 0.13 [0.10-0.16]; P < 0.0001). Sensitivity analysis of 4 trials including only new-onset POAF showed similar summary estimates (OR 0.21, 95% CI [0.18-0.25]; P< 0.0001). TAVR is associated with a significantly lower risk of post-operative atrial fibrillation compared with SAVR in all strata. Further studies are needed to identify the contribution of post-operative atrial fibrillation to the differences in clinical outcomes after TAVR and SAVR.


Cerebrospinal fluid xanthochromia after pegasparaginase hepatotoxicity in B-cell acute lymphoblastic leukemia.
Patients with B-lineage acute lymphoblastic leukemia treated with pegasparaginase-containing regimens can develop hepatotoxicity related to it. The systemic hyperbilirubinemia due to hepatotoxicity can lead to the development of CSF xanthochromia.


[Meta-analysis on the association of ACE/ID polymorphism and essential hypertension in Chinese population].
To study on the association of the insertion(I)/deletion(D) polymorphism of the angiotensin-converting enzyme gene intron 16 (ACE/ID) and essential hypertension(EH) in Chinese population by the means of meta-analysis. Odds ratios of ACE/ID genotype distributions in EH patients against healthy control were analysed. All the relevant studies were identified, poor-qualified studies were eliminated, and the risk of publication bias was excluded. The meta-analysis software, REVMAN3.1, was applied for investigating heterogeneity among individual studies and summarising effects across studies. A total of 1,612 cases and 1,710 controls from 18 studies were included. No heterogeneity among the studies has been found. The frequencies of the ACE DD, ID and II genotypes were 23%, 41%, and 36% in cases and 19%, 46% and 35% in controls respectively. The pooled odds ratio (with 95% CI) of DD vs ID + II is 1.37(1.15-1.63) (P < 0.01), while the pooled odds ratio of II vs ID + DD is 0.96 (0.83-1.12) (P > 0.05). In Chinese population (mainly the Hans), DD genotype is associated with the increased risk of EH.


S-glutathionylation, friend or foe in cardiovascular health and disease.
Glutathione is a low molecular weight thiol that is present at high levels in the cell. The high levels of glutathione in the cell make it one of the most abundant antioxidants contributing to cellular redox homeostasis. As a general rule, throughout cardiovascular disease and progression there is an imbalance in redox homeostasis characterized by reactive oxygen species overproduction and glutathione underproduction. As research into these imbalances continues, glutathione concentrations are increasingly being observed to drive various physiological and pathological signaling responses. Interestingly in addition to acting directly as an antioxidant, glutathione is capable of post translational modifications (S-glutathionylation) of proteins through both chemical interactions and enzyme mediated events. This review will discuss both the chemical and enzyme-based S-glutathionylation of proteins involved in cardiovascular pathologies and angiogenesis.


Pituitary adenylate-cyclase-activating polypeptide (PACAP) binding sites and PACAP/vasoactive intestinal polypeptide receptor expression in human pituitary adenomas.
Pituitary adenylate-cyclase-activating polypeptide (PACAP) stimulates release of several anterior pituitary hormones by interacting with PACAP receptors on pituitary cells. To learn more about the distribution and possible regulatory roles of PACAP and its receptors in human pituitary adenomas, we investigated the expression of vasoactive intestinal polypeptide (VIP) and PACAP binding sites using receptor autoradiography, PACAP and PACAP/VIP receptor (PVR) mRNAs by reverse transcription polymerase chain reaction (RT-PCR), conventional in situ hybridization, and catalyzed reporter deposition in situ hybridization (CARD-ISH) analyses. PACAP mRNA was expressed in normal human hypothalamus, which was used as a positive control, but not in pituitary adenomas. Receptor autoradiography showed PACAP types I and II binding sites in all groups of pituitary adenomas, except prolactinomas. The highest levels were present in gonadotroph and null cell adenomas. PVR-2 mRNA was expressed in normal pituitaries and in all groups of pituitary adenomas by RT-PCR, whereas PVR-1 and -3 mRNAs were expressed in all groups of pituitary adenomas, except for most prolactinomas. Conventional in situ hybridization studies with digoxigenin-labeled probes demonstrated weak staining for PVR-1, -2, and -3 mRNAs in most tissues. The CARD-ISH technique, which increased the sensitivity of the in situ hybridization method, also revealed PVR-2 mRNA expression in all adenomas, whereas PVR-1 and -3 mRNAs were detected in nearly all adenomas except for prolactinomas. The presence of PACAP mRNA in the hypothalamus, but not in normal anterior pituitary or in pituitary adenomas, and the differential expression of PVRs in adenomas indicate a selective regulatory endocrine and paracrine role of PACAP in normal and neoplastic anterior pituitary cells.


Kinetics and mechanism of the reactions of S-2,4-dinitrophenyl 4-substituted thiobenzoates with secondary alicyclic amines.
[reaction: see text] The title reactions, in 44 wt % ethanol-water at 25.0 degrees C, exhibit slightly curved Brønsted-type plots (log kN versus pKa of amines) with slopes beta1 = 0.1-0.44 (at high pKa) and beta2 ca. 0.7 (at low pKa). The magnitude of some of these slopes, together with the fact that the curvature center (pKa(0) = 9.5-10.8) does not change with the electronic effects of the benzoyl substituent, suggests that these reactions are not stepwise, but concerted.


Valinomycin-based K+ selective microelectrodes with low electrical membrane resistance.
A valinomycin-based membrane phase for microelectrodes with relatively low electrical membrane resistances is described. Microelectrodes with tip diameters of about 1 micron exhibit resistances of about 10(10) omega. Extremely high K+ selectivities are obtained, e.g. a rejection of Na+ by a factor of 5000 and of acetylcholine by a factor of 3400. At a constant background of 140 and 500 mM Na+, the detection limit of the K+ sensor is at 1.6 X 10(-5) and at 2.5 X 10(-5) M K+, respectively.


Reconstructive options for the medial canthus and eyelids following tumor excision.
General principles provide the framework for eyelid and periorbital reconstruction following tumor excision. Eyelid tumors involving the medial canthus region and/or lacrimal system add to the complexity of reconstructive planning. The nature of the tumor, patient and tissue factors, and surgeon preference guide repair design choices. Reconstructive considerations and options following medial canthal tumor resection are described.


Patella baja after intramedullary nailing of tibial fractures, using an infrapatellar/transtendinous approach, predicts worse patient reported outcome.
After intramedullary nailing of tibial shaft fractures using an infrapatellar/transtendinous approach, several patients suffer anterior knee pain. We suspect that the approach is associated with soft tissue scars and the development of a postoperative patella baja. The goal of the study is to investigate whether the development of patella baja is associated with worse subjective outcomes. We retrospectively analyzed all patients in our orthopedic trauma department between 2011 and 2020 who underwent tibial fracture fixation via intramedullary nailing via an infrapatellar/transtendinous approach. Pre- and postoperative lateral knee x-rays were evaluated by measurement of the Insall-Salvati Index, and nail tip position. All patients were asked to answer the self-assessment Kujala questionnaire and Lysholm questionnaire. We included 78 patients (age: 44 ± 18 years) with a minimum follow-up of 12 months. Mean follow up was 59 ± 25 months. We included 50 male and 28 female patients. Patella baja detected by Insall-Salvati Index could be observed in 8 (10.3%) patients. Patients with patella baja showed significant worse function measured by the Kujala score 54 ± 18 vs. 80 ± 14 (p < 0.01). Likewise, Lysholm score did show significant differences between both groups (60 ± 24 vs. 86 ± 11; p < 0.01). Nail tip position was not associated with worse subjective function. Patella baja in patients after tibial intramedullary nailing via an infrapatellar/transtendinous approach, is associated with worse subjective function and increased pain.


TiO2 nanoparticles in the marine environment: Impact on the toxicity of phenanthrene and Cd2+ to marine zooplankton Artemia salina.
The impact of manufactured nanoparticles on the toxicity of co-existing pollutants in aquatic environments has raised increasing concerns. However, the toxicity of polycyclic aromatic hydrocarbons or metal ions in the presence of titanium dioxide nanoparticles (nTiO2) to marine zooplankton has been rarely reported. In the present study, the impacts of nTiO2 on the toxicity of phenanthrene (Phe) and cadium (Cd2+) to Artemia salina, a model marine zooplankton, were investigated. Although nTiO2 alone exerted a limited toxicity to A. salina within 48h of exposure, nTiO2 strongly altered the toxicity of Phe and Cd2+ to A. salina. Compared with the individual toxicities of pollutants to A. salina, the toxicities of Phe and Cd2+ increased by 2.0% and 12.2%, respectively, in the presence of 5mg/L nTiO2, but decreased by 24.5% and 57.1%, respectively, in the presence of 400mg/L nTiO2. These concentration-dependent impacts of nTiO2 on the toxicity of Phe or Cd2+ might be attributed to the concurrent functions of several interrelated factors including the adsorption of pollutants on nTiO2, the nTiO2-faciliated bioaccumulation of pollutants, the limited gut volume in organisms, and the aggregation and sedimentation behaviors of nTiO2. These results presented in the study could help understand the effects of manufactured nanomaterials in marine environments.


[Successful treatment of acute promyelocytic leukemia in a pregnant patient with all-trans retinoic acid and chemotherapy resulting in a safe delivery].
A 32-year-old woman at 21 gestational weeks was admitted because of leukocytosis with DIC. She was diagnosed as having acute promyelocytic leukemia and treated with all-trans retinoic acid (70 mg/body) in combination with daunorubicin and cytosine arabinoside. She achieved complete remission, and continuously received a second treatment with daunorubicin and cytosine arabinoside. Cesarean section was performed, and a live male infant was born in the 30th week of pregnancy. The mother and baby have progressed excellently to date. In a such case, the choice of treatment and time of birth should be considered depending on the individual situation.


Inhibitory effects of procaine on the contractile responses of the guinea-pig taenia caecum to acetylcholine, substance P and potassium chloride.
The effect of procaine on the contractile responses to acetylcholine, substance P and KCl was investigated using the isolated guinea-pig taenia caecum. In normal Tyrode solution (37 degrees C), procaine (10-100 mumol/l) caused a parallel shift to the right of only the dose-response curve of acetylcholine (pA2 value, 5.11). The pA2 value of procaine against acetylcholine was not significantly affected by increasing the Ca concentration in the bathing solution from 0.9 to 7.2 mmol/l. On the other hand, a high concentration of procaine (10 mmol/l) caused a transient contraction of the taenia caecum, but completely suppressed contractions to all concentrations of the agonists. In K-depolarized preparations, procaine (1-10 mmol/l) shifted the dose-response curve for the CaCl2-induced contraction to the right. Substance P (3 mumol/l)-induced contraction of the taenia caecum incubated with Ca-free EGTA (0.1 mmol/l) solution (20 degrees C) was markedly reduced by procaine (10 mmol/l). Using the single sucrose-gap technique, it was found that procaine (10 mmol/l) produced a membrane depolarization and increases in both amplitude and frequency of spontaneous spike discharge. These potential changes were still observed even after the procaine-induced contraction had disappeared. The spike discharges and contraction caused by procaine were abolished in the presence of a Ca-entry blocker, verapamil (10 mumol/l).(ABSTRACT TRUNCATED AT 250 WORDS)


Nonlinear Dimensionality Reduction by Minimum Curvilinearity for Unsupervised Discovery of Patterns in Multidimensional Proteomic Data.
Dimensionality reduction is largely and successfully employed for the visualization and discrimination of patterns, hidden in multidimensional proteomics datasets. Principal component analysis (PCA), which is the preferred approach for linear dimensionality reduction, may present serious limitations, in particular when samples are nonlinearly related, as often occurs in several two-dimensional electrophoresis (2-DE) datasets. An aggravating factor is that PCA robustness is impaired when the number of samples is small in comparison to the number of proteomic features, and this is the case in high-dimensional proteomic datasets, including 2-DE ones. Here, we describe the use of a nonlinear unsupervised learning machine for dimensionality reduction called minimum curvilinear embedding (MCE) that was successfully applied to different biological samples datasets. In particular, we provide an example where we directly compare MCE performance with that of PCA in disclosing neuropathic pain patterns, hidden in a multidimensional proteomic dataset.


Complete mitochondrial genome of the birch catkin bug Kleidocerys resedae resedae, as the first representative from the family Lygaeidae (Hemiptera: Heteroptera: Lygaeoidea).
Kleidocerys resedae resedae (Panzer, 1797) (Hemiptera: Heteroptera: Lygaeoidea: Lygaeidae: Ischnorhynchinae) is one of the destructive insect pests of birch and alder trees in Holarctic. Here we sequenced the complete mitochondrial genome of this pest, also representing the first mitochondrial genome of the family Lygaeidae. This genome is 14,688 bp long, with an A+T content of 76.0%, containing 37 typical animal mitochondrial genes and a control region. All genes were arranged in the same gene order as most of other Heteropteran species. Presently, the length of this mitochondrial genome is the shortest among all available Hemipterans, mainly because of its short control region (220 bp). The unusual intergenic spacer between tRNA-His and ND4, only shared by Lygaeoidea, was also found in K. resedae resedae, which supports that this spacer may be the synapomorphy of Lygaeoidea.


[Domestic and sexual violence against women. Implications of WHO guidelines for Germany].
Domestic violence and sexual violence are widespread and have serious health effects for those affected. If the problem is identified and confidence in responding exists, healthcare providers can make a significant contribution to support and intervention. In 2013 the WHO published evidence-based guidelines for responding to the issue in healthcare, training of healthcare providers and health policy. In principle, the guidelines confirm existing recommendations, best-practice guidelines and handbooks. They also encourage a review and further development-for example, regarding the issue of sexual violence. If and how the present recommendations are put into practice in healthcare and training of healthcare staff can currently be looked at only with the use of examples, given the lack of data in Germany. Examples from Berlin show that implementation is quite possible. However, there is a lack of clear mandate, of sustainability and of obligation. Existing good practice models are highly reliant on organisations' and employees' commitment. For Germany, the WHO guidelines indicate the need to develop national standards for healthcare in cases of domestic and sexual violence. A (legal) obligation for the healthcare system should be drawn up. A systematic embedding in training curricula of health care professions is needed. Quality assurance and a systematic evaluation of the practical implementation are required.


Calcium ion activation of the anion-conducting channel in the rat liver mitochondrial inner membrane.
Stimulation of the rat liver mitochondrial inner-membrane anion-conducting channel by aeration is dependent on the concentration of Ca2+ ions in the assay medium. Ca2+ activates anion conduction in both aerated and non-energised mitochondria but acts over a wider concentration range and produces a greater increase in anion-conductivity in aerated mitochondria. EGTA reverses Ca2+ stimulation but takes several seconds to act, indicating slow release of Ca2+ from the activation site possibly on the matrix side of the inner mitochondrial membrane. It is suggested that this channel may respond to hormone-induced changes in cytosolic Ca2+ concentration.


Correlation of diffusion tensor imaging parameters in the canine brain.
The goal of this study was to determine the degree to which ex vivo diffusion tensor imaging (DTI) parameters correlate to one another in white matter regions on very high resolution MR scans. Specifically, we hypothesized that radial diffusivity (RD) and apparent diffusion coefficient (ADC) would correlate more closely than either would correlate with fractional anisotropy (FA). We performed post mortem DTI imaging on three canine brains on a 7 T MR scanner (TR = 100 ms, NEX = 1, gradient amplitude = 600 mT/m, b = 1492-1,565 s/mm²) and generated maps of FA, RD, and ADC. We measured RD, FA and ADC within 14 regions of interest representative of various portions of white matter. We compared the three combinations of values, i.e., FA vs ADC, FA vs RD and ADC vs RD, using linear regression models. Linear regression demonstrated that RD was significantly correlated with FA (p << 0.01; R² = 0.3053) and also with ADC (p << 0.01; R² = 0.6755), but to a much greater degree. However, ADC was not significantly correlated with FA (p = 0.526; R² = 0.101). Our findings suggest that both RD and ADC reflect similar cytoarchitectural features, most likely that of myelination, whereas FA values likely reflect both myelination and additional microstructural features that constrain the diffusion of water in white matter.


Hard contact lens migration into the upper lid: an unexpected lid lump.
Contact lens migration into the upper lid is a rare complication of wearing a hard contact lens. We present a case in which the only complaint was the cosmetically unacceptable appearance of a lump in the upper lid. The 76-month duration of the lesion is, we believe, the longest so far described. The histology and possible natural history of the cyst are also discussed.


Neurocognitive deficits in a patient with small cell lung cancer: a case report.
The neurocognitive deficits associated with small cell lung cancer include metastasis to brain and paraneoplastic syndrome. The patients are also predisposed to herpes encephalitis due to immunosuppression and chemotherapy. We report a case of 72 year old female diagnosed with small cell lung cancer started with memory deficits, ataxia, vertigo, and hearing loss. The paraneoplastic work-up returned as anti-Hu antibody positive. The MRI brain showed area of edema and inflammation right medial temporal lobe as well as enhancement in the underlying meningi. Although PCR/HSV of CSF was negative, the patient was empirically treated with IV acyclovir and showed significant improvement and was discharged in good condition. The case highlights the importance of keeping broad minded approach in treating patients with serious malignant diseases. The case also call attention to the use of empiric therapy in possible life threatening diseases such as Herpes encephalitis.


Mechanisms of inverse agonism at histamine H(2) receptors - potential benefits and concerns.
It is well established that histamine exerts its effects by activating histamine receptors that belongs to the family of seven transmembrane G-protein coupled receptors (GPCRs). Many ligands with important therapeutic actions that had been assumed to be antagonists at histamine H2 receptor have been shown to be inverse agonists. The mechanism whereby these drugs achieve their effects seems to be not unique. Theoretical models predict at least three ways in which inverse agonists can exert their action that are supported by experimental observations. These different mechanisms have crucial consequences on basic pharmacology and clinical treatments. The pharmacological models, the feasible mechanisms of action of H2 inverse agonists, findings about molecular basis of tiotidine inverse agonism in particular, and their impact on clinical protocols will be discussed.


Epithelial (inverted) papilloma: a correlated radiological--histological study.
The radiological and pathological features in 14 cases of epithelial papilloma are described. The typical radiological findings are a mass in the nares and sinus opacification, usually on the same side. Occasionally, extension of the mass into the nasopharynx is observed. Bone destruction may be present in epithelial papilloma, possibly due to pressure erosion. In the presence of carcinoma, bone destruction may be due to direct invasion.


Leaf absorptances of Mohave and Sonoran desert plants.
Leaf absorptances to solar radiation in the 400-700 nm (photosynthetically useful wavelengths) are presented for a diversity of species in the Mohave and Sonoran Deserts of North America. As a life form shrubs are shown to have the widest range of absorptance, with perennial herbs and cacti exhibiting a smaller range, and very little variation in leaf absorptances among trees and annuals. The measurement of leaf absorptance at 625 nm is shown to be the same as the leaf absorptance to solar radiation over the 400-700 nm. Over a wide range of species and absorptances, the total solar leaf absorptance (400-3,000 nm) is shown to be closely related to the 400-700 nm leaf absorptance.


ERP evidence for telicity effects on syntactic processing in garden-path sentences.
Verbs contain multifaceted information about both the semantics of an action, and potential argument structures. Linguistic theory classifies verbs according to whether the denoted action has an inherent (telic) end-point (fall, awaken), or whether it is considered homogenous, or atelic (read, worship). The aim of our study was to examine how this distinction influences on-line sentence processing, investigating the effects of verbal telicity on the ease of syntactic re-analysis of Object reduced relative clauses. Event-related brain potentials (ERPs) were recorded from 22 English speakers as they read sentences in which the main verb was either telic or atelic, e.g., "The actress awakened/worshipped by the writer left in a hurry". ERPs elicited by telic and atelic verbs, the preposition "by" introducing the second argument (Agent), and the second argument itself, e.g., "writer", were compared. Additionally, participants were grouped according to receptive syntactic proficiency: normal (NP) or high (HP). ERPs from the NP group first diverged at the second argument, with the atelic condition eliciting larger amplitude negativity at the N100, and continuing to the P200 interval. In contrast, ERPs from the HP group first diverged earlier in the sentence, on the word "by". ERPs elicited by "by" in the atelic condition were also characterized by increased negativity, in this case significant at P200 and Anterior Negativity between 320 and 500ms post stimulus onset. Our results support the postulated conceptual/semantic distinction underlying the two verb categories, and demonstrate that world-knowledge about actions designated by verbs and syntactic proficiency are reflected in on-line processing of sentence structure.


Cytotoxic chalcones and antioxidants from the fruits of a Syzygium samarangense (Wax Jambu).
Bioassay-guided fractionation of the methanolic extracts of the pulp and seeds of the fruits of Syzygium samarangense Merr. & Perry (Blume) led to the identification of four cytotoxic compounds and eight antioxidants on the basis of HPLC-PDA analysis, MS, and various NMR spectroscopic techniques. Three C-methylated chalcones, 2',4'-dihydroxy-3',5'-dimethyl-6'-methoxychalcone (1), 2',4'-dihydroxy-3'-methyl-6'-methoxychalcone (stercurensin, 2), and 2',4'-dihydroxy-6'-methoxychalcone (cardamonin, 3), were isolated and displayed cytotoxic activity (IC(50) = 10, 35, and 35 μM, respectively) against the SW-480 human colon cancer cell line. Also a number of known antioxidants were obtained including six quercetin glycosides: reynoutrin (4), hyperin (5), myricitrin (6), quercitrin (7), quercetin (9), and guaijaverin (10), one flavanone: (S)-pinocembrin (8), and two phenolic acids: gallic acid (11) and ellagic acid (12).


Three-dimensional exoscope-assisted single-stage tracheal resection.
The three-dimensional (3D) 4K exoscope is a surgical tool recently introduced in numerous fields of otolaryngology, such as microvascular surgery, otology, and laryngology. However, other surgical fields may also benefit from this technology. In this case, a single-stage tracheal resection was planned with the aid of the 3D 4K exoscope, in a 75-year-old female with post-tracheostomy tracheal stenosis. High-quality magnification of the surgical field was obtained, with facilitated skeletonization of the laryngotracheal axis. The exoscope provided greater involvement in surgery and allowed more interactions among all operating room personnel and learners, as they could access the same field of view of the first surgeon, as well as perceiving depth of the surgical field with 3D technology. The exoscope represents a valid application in open surgery performed for laryngotracheal stenosis, with advantages of enhancing training and education, allowing precise surgical dissection, and reducing risks of iatrogenic damage to surrounding structures.


Cervical cerclage for the temporary treatment of patients with placenta previa.
Cervical cerclage as a temporizing measure for the treatment of patients with placenta previa was evaluated in 25 patients admitted to the hospital for vaginal bleeding between 24-30 weeks' gestation and sonographic evidence of a placenta previa. The patients were randomly assigned to either cerclage (13) or conventional management (12). Cerclage patients had significantly better perinatal outcome, as indicated by more advanced gestational age at the time of delivery (34.9 +/- 3.0 versus 31.6 +/- 2.9 weeks; P = .02), larger birth weight (2709 +/- 511 versus 1812 +/- 506 g; P = .002), and fewer neonatal complications (two of 13 versus ten of 12 infants; P = .001). Maternal bleeding was more frequent and severe for patients in the control group. The total hospital cost was less for cerclage patients than for those receiving conventional expectant management ($9898 +/- 3943 versus $27,271 +/- 9901; P = .02). These results support the use of cervical cerclage for the treatment of patients with symptomatic placenta previa early in gestation.


Toxicokinetics of zinc oxide nanoparticles and food grade bulk-sized zinc oxide in rats after oral dosages.
The increasing application of zinc oxide nanoparticles (ZnO NPs) in consumer products has raised concerns about the potential health risks in human. It is crucial to understand the toxicokinetic information of ZnO NPs, especially the differences between NPs and non-nano form material. This study investigated the toxicokinetic profile of ZnO NPs and food grade bulk-sized ZnO in rats after single or repeated oral dosages. For single oral administration of ZnO suspensions at 350 mg/kgbw, the Zn content in blood and tissues showed no elevation, the majority of ZnO particles were eliminated via feces within 48 h. For repeated oral exposure to ZnO suspensions at 350 mg/kgbw or ZnSO4 solution at 700 mg/kgbw for 90 days, elevated Zn levels were observed in liver, kidney, and bone in all three treatment groups, the Zn level recovered to normal level in liver and kidney, but not in bone, after a recovery period. ZnO NPs and bulk-sized ZnO showed similarity in toxicokinetics in rats, regardless of exposure duration or gender. ZnO particles shared a similar biodistribution profile with ZnSO4, and were likely to be absorbed mostly in ionic forms.


[DNA impulse cytophotometry measurements in head and neck tumors. Initial results of a correlation with clinical stage, therapeutic response and pattern of recurrence].
The DNA index and proliferation rate (percentage of S-phase cells) of 52 head and neck tumours were analysed by flow cytometry. Thirty-one (60%) of these tumours were aneuploid, 21 (40%) diploid. The distribution of aneuploid tumours was nearly equal in all T-stages. In contrast, the number of aneuploid tumours increased with higher N-stages. Locoregional recurrences developed more often (69%) in aneuploid tumours than in diploid tumours (54%). Furthermore, recurrence presented earlier (median 5 months) than in the latter (median 11 months). Regional recurrences were mainly observed in aneuploid tumours, local recurrences in diploid tumours.


Role of tumour-associated N-glycolylated variant of GM3 ganglioside in cancer progression: effect over CD4 expression on T cells.
Gangliosides have diverse biological functions including modulation of immune system response. These molecules are differentially expressed on malignant cells compared with the corresponding normal ones and are involved in cancer progression affecting, in different ways, the host's anti-tumour specific immune responses. Although in humans the N-glycolylated variant of GM3 ganglioside is almost exclusively expressed in tumour tissues, the significance of this glycolipid for malignant cell biology remains obscure, while for NAcGM3 strong immune suppressive effects have been reported. The present work demonstrates, for the first time, the capacity of NGcGM3 ganglioside to down-modulate CD4 expression in murine and human T lymphocytes, especially in non-activated T cells. Thirty and tenfold reductions in CD4 expression were induced by purified NGcGM3 ganglioside in murine and human T lymphocytes, respectively. The CD4 complete recovery in these cells occurred after 48 h of ganglioside removal, due to neo-synthesis. Restored T cells kept similar sensitivity to ganglioside-induced CD4 down-modulation after a new challenge. In addition, a clear association between NGcGM3 insertion in lymphocyte plasma membranes and the CD4 down-modulation effect was documented. Notably, a possible role of this ganglioside in tumour progression, taking advantage of the X63 myeloma model, was also outlined. The relevance of these findings, characterizing NGcGM3 as a possible tumour immunesurveillance inhibitor and supporting the reason for its neo-expression in certain human cancers, is contributing to this unique heterophilic ganglioside validation as target for cancer immunotherapy.


Acidic microenvironment responsive polymeric MOF-based nanoparticles induce immunogenic cell death for combined cancer therapy.
The complex tumor microenvironment and non-targeting drugs limit the efficacy of clinical tumor therapy. For ensuring the accurate delivery and maximal effects of anticancer drugs, it is important to develop innovative drug delivery system based on nano-strategies. In this study, an intracellular acidity-responsive polymeric metal organic framework nanoparticle (denoted as DIMP) has been constructed, which can co-deliver the chemotherapy agent of doxorubicin (DOX) and phototherapy agent of indocyanine green (ICG) for breast carcinoma theranostics. Specifically, DIMP possesses a suitable and stable nanometer size and can respond to the acidic microenvironment in cells, thus precisely delivering drugs into target tumor sites and igniting the biological reactions towards cell apoptosis. Following in vivo and in vitro results showed that DIMP could be effectively accumulated in tumor sites and induced powerful immunogenic cell death (ICD) effect. The designed DIMP displayed its effectiveness in combined photo-chemotherapy with auxiliary of ICD effect under a multimodal imaging monitor. Thus, the present MOF-based strategy may offer a potential paradigm for designing drug-delivery system for image-guided synergistic tumor therapy.


A comparison between heparin and low-dose aspirin as adjunctive therapy with tissue plasminogen activator for acute myocardial infarction. Heparin-Aspirin Reperfusion Trial (HART) Investigators.
We report the results of the Heparin-Aspirin Reperfusion Trial, a collaborative study comparing early intravenous heparin with oral aspirin as adjunctive treatment when recombinant tissue plasminogen activator (rt-PA) is used for coronary thrombolysis during acute myocardial infarction. Two hundred five patients were randomly assigned to receive either immediate and then continuous intravenous heparin (starting with a 5000-unit bolus; n = 106) or immediate and then daily oral aspirin (80 mg; n = 99) together with rt-PA (100 mg intravenously over a six-hour period) initiated within six hours of the onset of symptoms. We evaluated the patency of the infarct-related artery by angiography 7 to 24 hours after beginning rt-PA infusion, the frequency of reocclusion of the artery by repeat angiography on day 7, and ischemic or hemorrhagic complications during the hospital stay. At the time of the first angiogram, 82 percent of the infarct-related arteries in the patients assigned to heparin were patent, as compared with only 52 percent in the aspirin group (P less than 0.0001). Of the initially patent vessels, 88 percent remained patent after seven days in the heparin group, as compared with 95 percent in the aspirin group (P not significant). The numbers of hemorrhagic events (18 in the heparin and 15 in the aspirin group) and recurrent ischemic events (8 in the heparin and 2 in the aspirin group) were similar in the two groups. Coronary patency rates associated with rt-PA are higher with early concomitant systemic heparin treatment than with concomitant low-dose oral aspirin. This observation has important implications for clinical practice and should be considered in the design and interpretation of clinical trials involving coronary thrombolytic therapy.


Corrigendum to "Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules" [FEBS Open Bio 4 (2014) 571-583].
[This corrects the article DOI: 10.1016/j.fob.2014.05.005.].


A neoplasm with pancreatic and hepatocellular differentiation presenting with subcutaneous fat necrosis.
A neoplasm demonstrating both pancreatic and hepatic phenotypes is described. The tumor, from a 53-year-old woman with the syndrome of subcutaneous fat necrosis and arthropathy, was studied histologically, immunohistochemically, ultrastructurally, and biochemically. The clinical features of this case can be explained by the production of large amounts of lipase by the tumor. The hepatocellular properties of the tumor included characteristic morphology and the synthesis of catalase. The pancreatic properties of the tumor included the production of pancreatic lipase. This neoplasm would appear to be analogous to animal models in which the transdifferentiation of pancreatic acinar cells and hepatocytes has been demonstrated. Although the bulk of the tumor was present in the liver, the authors believe the tumor arose from the pancreas. The distinction between differentiation and site of origin of tumors is discussed.