Anti-proliferative effects of tumor necrosis factor, gamma interferon and 5-fluorouracil on human colorectal carcinoma cell lines.
We have previously utilized a bank of diverse human colorectal carcinoma cell lines to assess the synergistic antiproliferative effect of tumor necrosis factor (TNF) and IFN-gamma (IFN-gamma) in combination. In this study, we used 3 of these cell lines (HCT 116, SKO1 and VACO 9P) to study the growth-inhibitory effects of TNF and IFN-gamma (TNF/IFN-gamma) on these cells when administered in conjunction with 5-fluorouracil (5-FU). All 3 cell lines were sensitive to suprapharmacologic concentrations of 5-FU. However, the 3 lines varied in their sensitivities to clinically achievable concentrations of 5-FU. Concentrations of 0.1 microgram/ml of 5-FU administered for 96 hr, and 50 micrograms/ml administered for 1 hr, inhibited the growth of HCT 116 cells by 20% and 77%, that of SKCO1 cells by 25% and 66%, and that of VACO 9P cells by 25% and 55%, respectively. All 3 cell lines were sensitive to the anti-proliferative effects of TNF/IFN-gamma in a dose-dependent and duration-dependent fashion. TNF/IFN-gamma was administered for 1 hr every other day on days 1, 3 and 5 to the 3 cell lines. Cells were also exposed to 5-FU, administered either concomitantly for 96 hr, or for 1 hr on day 1. The addition of TNF/IFN-gamma to clinically achievable concentrations of 5-FU in both schedules resulted in additive cytotoxicity. For example, the addition of 10 ng/ml of both TNF and IFN-gamma to 96 hr of 0.1 microgram/ml 5-FU resulted in 10%, 5%, and 20% of control growth for the HCT 116 cell line, SKCO1 cell line, and VACO 9P cell line, respectively. The addition of 10 ng/ml of both TNF and IFN-gamma to 1 hr of 50 micrograms/ml of 5-FU inhibited all cell growth in all 3 cell lines. We conclude that TNF/IFN-gamma and 5-FU can be combined to achieve higher anti-tumor activity than either 5-FU or TNF/IFN-gamma alone in this in vitro model, that the 3-drug combination has potent growth-inhibitory effects at pharmacologic concentrations which are not schedule-dependent, and that this combination warrants further study in clinical trials.


Characterization of a chemically synthesized RNA having the sequence of the yeast initiator tRNA(Met).
A 75-unit long oligoribonucleotide corresponding to the sequence of the Saccharomyces cerevisiae initiator tRNA was synthesized chemically. The crude RNA was purified, and the sequence was verified by RNA sequencing techniques. A particularly useful purification step involved hydrophobic chromatography on BND-cellulose. The purified RNA could be aminoacylated to 28% of a bona fide initiator tRNA(Met) sample and threonylated to 76% of the level observed with native tRNA(fMet) from E. coli.


Kinetics of oxygen-18 exchange between inorganic phosphate and water catalyzed by myosin subfragment 1, using the 18O shift in 31P NMR.
The time course of oxygen-18 exchange between [18O]Pi and normal water, catalyzed by myosin subfragment 1 in the presence of MgADP, was followed using the shift in 31P NMR caused by the presence of oxygen-18 bound to the phosphorus. Essentially all molecules of [18O]Pi that bind to the enzyme undergo complete exchange and are released as [16O4]Pi. Exchange probably occurs by formation of myosin.ATP from a myosin.ADP.Pi complex and is rapid relative to release of Pi from this complex. The kinetics of exchange give a value for the rate constant for binding Pi to myosin.ADP of 0.23 M-1 S-1 (pH 8.0, 22 degrees C). This value is consistent with exchange occurring by reversal of the ATP-ase reaction back to the myosin.ATP complex.


Regulation of neuronal pH by the metabotropic Zn(2+)-sensing Gq-coupled receptor, mZnR/GPR39.
Synaptically released Zn(2+) acts as a neurotransmitter, in part, by activating the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor (mZnR/GPR39). In previous work using epithelial cells, we described crosstalk between Zn(2+) signaling and changes in intracellular pH and/or extracellular pH (pHe). As pH changes accompany neuronal activity under physiological and pathological conditions, we tested whether Zn(2+) signaling is involved in regulation of neuronal pH. Here, we report that up-regulation of a major H(+) extrusion pathway, the Na(+)/H(+) exchanger (NHE), is induced by mZnR/GPR39 activation in an extracellular-regulated kinase 1/2-dependent manner in hippocampal neurons in vitro. We also observed that changes in pHe can modulate neuronal mZnR/GPR39-dependent signaling, resulting in reduced activity at pHe 8 or 6.5. Similarly, Zn(2+)-dependent extracellular-regulated kinase 1/2 phosphorylation and up-regulation of NHE activity were absent at acidic pHe. Thus, our results suggest that when pHe is maintained within the physiological range, mZnR/GPR39 activation can up-regulate NHE-dependent recovery from intracellular acidification. During acidosis, as pHe drops, mZnR/GPR39-dependent NHE activation is inhibited, thereby attenuating further H(+) extrusion. This mechanism may serve to protect neurons from excessive decreases in pHe. Thus, mZnR/GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain. We show that the postsynaptic metabotropic Zn(2+)-sensing Gq protein-coupled receptor (mZnR/GPR39) activation induces up-regulation of a major neuronal H(+) extrusion pathway, the Na(+)/H(+) exchanger (NHE), thereby enhancing neuronal recovery from intracellular acidification. Changes in extracellular pH (pHe), however, modulate neuronal mZnR/GPR39-dependent signaling, resulting in reduced activity at pHe 8 or 6.5. This mechanism may serve to protect neurons from excessive decreases in pHe during acidosis. Hence, mZnR/GPR39 signaling provides a homeostatic adaptive process for regulation of intracellular and extracellular pH changes in the brain.


The evolution of gene regulation underlies a morphological difference between two Drosophila sister species.
Understanding the mechanisms underlying the morphological divergence of species is one of the central goals of evolutionary biology. Here, we analyze the genetic and molecular bases of the divergence of body pigmentation patterns between Drosophila yakuba and its sister species Drosophila santomea. We found that loss of pigmentation in D. santomea involved the selective loss of expression of the tan and yellow pigmentation genes. We demonstrate that tan gene expression was eliminated through the mutational inactivation of one specific tan cis-regulatory element (CRE) whereas the Tan protein sequence remained unchanged. Surprisingly, we identify three independent loss-of-function alleles of the tan CRE in the young D. santomea lineage. We submit that there is sufficient empirical evidence to support the general prediction that functional evolutionary changes at pleiotropic loci will most often involve mutations in their discrete, modular cis-regulatory elements.


Palmatine regulates bile acid cycle metabolism and maintains intestinal flora balance to maintain stable intestinal barrier.
Palmatine (PAL) is a natural isoquinoline alkaloid that has been widely used in the pharmaceutical field. The current study aimed to investigate the function of PAL in improving hyperlipidemia induced by high-fat diet (HFD) in rats. Biochemical analysis of triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDLC) was performed on rats. Total bile acid (TBA) and stool TC and TBA were also measured to assess the changes in total bile acid excretion. RT-qPCR was employed to detect the expression of genes related to bile acid metabolism, and the Western blot assay was used to detect the levels of CYP7A1, ZO-1, ZO-2, and Claudin-1. The siRNA experiment was employed to further investigate whether PAL regulated CYP7A1 through PPARα. Lipopolysaccharide (LPS) and FITC-dextran (FD-4) were also tested to assess the intestinal permeability. AL-treated rats had lower TC, TG, LDL-C levels, lower serum TBA levels, and increased fecal TBA and TC levels. Furthermore, CYP7A1 protein expression was up-regulated in PAL-treated rats. Additionally, PAL regulated bile acid metabolism by up-regulating the expression of CYP7A1 and PPARα and down-regulating the expression of FXR. Besides, the area of plasma FD-4 and LPS content in the PAL group were reduced, and the expression of proteins ZO-1, ZO-2 and Claudin-1 related to intestinal permeability was increased. All in all, PAL could mediate the PPARα-CYP7A1 pathway to maintain the balance of intestinal flora, regulate the bile acid metabolism, and reduce the blood lipids of rats, thereby protecting against hyperlipidemia.


Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro.
Previous studies suggested that the postsynaptic GABA(B) receptors of deep cerebellar nuclear neurons of adult rats were not activated by selective GABA(B) receptor agonist baclofen or endogenous GABA released by cerebellar cortical Purkinje cells, although the receptors have been demonstrated to exist in the deep cerebellar nuclei. In this study, cerebellar slices of adult rats were prepared for testing effects of GABA, baclofen and muscimol (selective GABA(A) receptor agonist) on cerebellar interpositus nucleus (IN) neurons. Perfusing slices with GABA (10-1000 microM), baclofen (1-30 microM) and muscimol (1-100 microM) respectively produced a dose-dependent inhibitory response on the IN neurons (n = 39, 62 and 50), which was not blocked by low-Ca(2+)/high-Mg(2+) medium (n = 5, 6 and 6), supporting a direct postsynaptic action of these GABAergic agonists. Moreover, both selective GABA(B) receptor antagonist CGP35348 and selective GABA(A) receptor antagonist bicuculline were capable of partially blocking the inhibitory response of IN neurons to GABA (n = 14 and 11), suggesting that the GABA-induced inhibition may contain two components, a GABA(B) receptors-mediated component and a GABA(A) receptors-mediated one. Further experiments revealed that not only muscimol (n = 50) but also baclofen (n = 62) suppressed IN cells' activity. The baclofen-induced inhibition was selectively blocked by CGP35348 (n = 12) but not by bicuculline (n = 8), whereas the muscimol-induced inhibition was selectively antagonized by bicuculline (n = 8) instead of CGP35348 (n = 9). These results indicate that GABA(B) receptors in the IN neurons can be activated not only by GABA but also by baclofen, suggesting that besides GABA(A) receptors, GABA(B) receptors may also be involved in mediating the inhibitory effect of GABA on cerebellar IN neurons of adult rats.


[Interspecies study of statistical correlations existing between the pineal gland size and weight and brain and body weight in two groups of mammals. Interspecies study of correlations between the pineal gland and brain in the rat and in man].
Network analysis procedures have been applied to study the cell patterns on the dorso medial and ventral lateral formation of the inferior colliculus of different species, i-e: Cat, Tat and Monkey. The results suggests the existence of important interspecific differences, more particularly in the primates. These differences are more obvious in the dorso medial formation. The functionnal implications of these results are discussed.


Two case reports: night terrors with sleepwalking--a potentially lethal disorder.
Two cases of severe night terrors with sleepwalking in adults are described. In one of these, an episode resulted in three deaths; in the other, there was serious concern of death and bodily harm. Both men were employed, married, and functioning well without serious psychopathology. Neither could be given a definite DSM-III diagnosis, though both had some features of compulsive personality disorder. Both improved considerably with treatment.


Accurate perceptions do not need complete information to reflect reality.
Social reality of a group emerges from interpersonal perceptions and beliefs put to action under a host of environmental conditions. By extending the study of fast-and-frugal heuristics, we view social perceptions as judgment tools and assert that perceptions are ecologically rational to the degree that they adapt to the social reality. We maintain that the veracity of both stereotypes and base rates, as judgment tools, can be determined solely by accuracy research.


A retrospective analysis of computed tomography findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation.
The purpose of this study was to review the high-resolution computed tomography (CT) findings in patients with pulmonary complications after allogeneic hematopoietic stem cell transplantation (HSCT), and to evaluate the relationship between CT findings and clinical outcomes. We collected the clinical data in 96 consecutive patients who underwent CT scan for pulmonary complications after allogeneic HSCT and analyzed the relationships among these clinical characteristics, CT findings and clinical responses. Radiologists who were blinded to clinical information evaluated the CT findings. In multivariate analyses, the presence of chronic graft-versus-host disease (GVHD) and non-segmental multiple consolidations were significantly associated with a poor response to antimicrobial therapies, and the disease risk was significantly associated with a poor corticosteroid response. In addition, the existence of cavity formation and pleural effusion were significantly associated with a fatal prognosis. Twenty-five patients underwent bronchoscopic examination and 4 of them also underwent transbronchial lung biopsy (TBLB), but diagnostic information was not obtained in 15 patients. There was no significant association between specific CT findings and the diagnosis based on bronchoscopic examination. No specific CT finding was identified as a predictor for either an antimicrobial response or for a corticosteroid response in this study. The presence of cavity formation and pleural effusion may predict a poor prognosis.


Benzyl-ammonium hepta-noate.
The title 1:1 stoichiometric salt, C7H10N(+)·C7H13O2 (-), is formed by proton transfer between hepta-noic acid and benzyl-amine. This combination contrasts to the recently published 2:1 acid-amine adduct of cation, anion and neutral acid molecule from the same components [Wood & Clarke (2013 ▶). Acta Cryst. E69, o346-o347]. There are N-H⋯O hydrogen bonds of moderate strength in the structure [the most important graph-set motifs are R (2) 4(8) and R (4) 4(12)], as well as weak C-H⋯O inter-actions.


Detection and imaging of bacterial biofilms with glutathione-stabilized gold nanoclusters.
Bacterial biofilms colonize chronic wounds and surfaces of medical devices, thus making the development of reliable methods for imaging and detection of biofilms crucial. Although fluorescent identification of bacteria is sensitive and non-destructive, the lack of biofilm-specific fluorescent dyes limits the application of this technique to biofilm detection. Here, we demonstrate, for the first time, that fluorescent glutathione-stabilized gold nanoclusters (GSH-AuNCs) without targeting ligands can specifically interact with extracellular matrix components of Gram-negative and Gram-positive bacterial biofilms resulting in fluorescent staining of bacterial biofilms. By contrast, fluorescent bovine serum albumin-stabilized gold nanoclusters and 11-mercaptoundecanoic acid - stabilized gold nanoclusters do not stain the extracellular matrix of biofilms. According to molecular docking studies, GSH-AuNCs show affinity to several targets in extracellular matrix, including amyloid-anchoring proteins, matrix proteins and polysaccharides. Some experimental evidence was obtained for the interaction of GSH-AuNCs with the lipopolysaccharide (LPS) that was isolated from the matrix of Azospirillum baldaniorum biofilms. Based on GSH-AuNCs properties, we propose a new fluorescent method for the measurement of biofilm biomass with a limit of detection 1.7 × 105 CFU/mL. The sensitivity of the method is 10-fold higher than the standard biofilm quantification with the crystal violet assay. There is a good linear relationship between the fluorescence intensity from the biofilms and the number of CFU from the biofilms in the range from 2.6 × 105 to 6.7 × 107 CFU/mL. The developed nanocluster-mediated method of biofilm staining was successfully applied for quantitative detection of biofilm formation on urinary catheter surface. The presented data suggest that fluorescent GSH-AuNCs can be used to diagnose medical device-associated infections.


Detection of collision events on curved trajectories: optical information from invariant rate-of-bearing change.
Previous research (Andersen & Kim, 2001) has shown that a linear trajectory collision event (i.e., a collision between a moving object and an observer) is specified by objects that expand and maintain a constant bearing (the object location remains constant in the visual field). In the present study, we examined the optical information for detecting a collision event when the trajectory was of constant curvature. Under these conditions, a collision event is specified by expansion of an object and a constant rate-of-bearing change. Three experiments were conducted in which trajectory curvature and display duration were varied while time to contact, speed, and initial image position of the collision objects were maintained. The results indicated that collision detection performance decreased with an increase in trajectory curvature and decreased with a decrease in display duration, especially for highly curved trajectories. In Experiment 3, we found that the presentation of a constant rate-of-bearing change in noncollision stimuli resulted in an increase in the false alarm rate. These results demonstrate that observers can detect collision events on curved trajectories and that observers utilize bearing change information.


Positive pre-transplant flow-panel reactive antibody detected after accelerated acute rejection with negative pre-transplant flow crossmatch.
A 30-yr-old woman underwent kidney transplantation from a flow cytometric lymphocyte crossmatch-negative donor. Immunosuppression consisted of tacrolimus, mycophenolate mofetil, basiliximab and three days of steroid. On day 5 post-transplant, she developed acute rejection and underwent anti-rejection therapy consisting of steroid pulse and deoxyspurgualin. Retrospective analyses of anti-human leukocyte antigen antibody revealed high flow panel reactive antibody (PRA) in the pre-transplant serum without donor specific antibody (DSA) and positive DSA at the time of rejection. Anti-rejection therapy was successful in treating cellular rejection but her graft function further deteriorated after three months post-transplant and graft biopsy revealed chronic allograft nephropathy with positive staining for C4d in peritubular capillary, suggesting the presence of chronic antibody-mediated rejection. Pre-transplant positive flow PRA without DSA may also be a risk for acute and chronic rejection.


Effects of fungal endophytes on the seed and seedling biology of Lolium perenne and Festuca arundinacea.
Many grasses are infected by endophytic fungi that grow intercellularly in leaves, stems, and flowers and are transmitted maternally by hyphal growth into ovules and seeds. The seed biology and seedling growth of endophyte-infected and uninfected perennial ryegrass (Lolium perenne) and tall fescue (Festuca arundinacea) were investigated under controlled environmental conditions. The percentage of filled seeds produced by infected tall fescue was over twice of uninfected tall fescue; infected and uninfected perennial reegrass had similar percentages. Weights of seeds from infected and uninfected plants were similar in both species. Seeds from infected plants of both species exhibited a higher rate of germination than seeds from uninfected plants. Shoot growth in the greenhouse was compared by making three sequential harvests of above-ground plant parts from infected and uninfected plants of both species. Infected perennial ryegrass plants produced significantly more biomass and tillers than uninfected plants after 6 and 10 weeks of growth and significantly more biomass after 14 weeks of growth. Infected tall fescue plants produced significantly more biomass and tillers than uninfected plants after 10 and 14 weeks of growth. The physiological mechanism of enhancement of growth is not known. The results of this study suggest that infected plants may have a selective advantage in populations with uninfected members.


Integrated structure-based activity prediction model of benzothiadiazines on various genotypes of HCV NS5b polymerase (1a, 1b and 4) and its application in the discovery of new derivatives.
This work presents the first structure-based activity prediction model for benzothiadiazines against various genotypes of HCV NS5b polymerase (1a, 1b and 4).The model is a comprehensive workflow of structure-based field template followed by guided docking. The field template was used as a pre-filter and a tool to provide hits in good orientation and position. It was created based on detailed molecular interaction field analysis which includes Topomer CoMFA, grid independent analysis and Superstar. On the other hand, Guided docking was used as a refinement and assessment tool. It was actively directed by two scores: Moldock score as an interaction descriptor (r(2)=0.65) and a template similarity score as a measure for accurate binding-mode compliance. The docking template was based on energy-based pharmacophore analysis. The whole procedure was formulated and tweaked for both screening (ROC of AUC=0.91) and activity prediction (r(2) of 0.8) for the genotype 1a. In order to widen the model scope, linear interaction energy was used as a tool for predicting activities of other genotypes based on the docked ligand poses while mutation binding energy was used to investigate the effect of each amino acid mutation in genotype 4. The model was applied for structure-based fragment hopping by screening a library designed by reaction enumeration. A top scoring hit was used to generate a focused library such that it has lower TPSA than the original class ligands and thus better pharmacokinetic properties. After that, experimental validation was carried out by the synthesis of this library and its biological evaluation which yielded compounds that exhibit EC(50) ranging from 1.86 to 23 μM.


Acetabular tilt correlates with acetabular version and coverage in hip dysplasia.
The rotational position of the acetabulum to the pelvis (acetabular tilt) may influence acetabular version and coverage of the femoral head. To date, the pathologic significance of acetabular tilt in hip dysplasia is unknown. We determined whether acetabular tilt in hip dysplasia is different from that in normal hips and whether this correlates with acetabular version and coverage. We measured the acetabular tilt angle on the lateral view of three-dimensional pelvic CT images of 40 patients (72 hips) with hip dysplasia. Forty normal hips from 40 patients were used as controls. The acetabular sector angle was measured as an index for acetabular coverage of the femoral head. The mean acetabular tilt angle was increased in dysplastic hips compared with controls. In dysplastic hips, a posteriorly rotated acetabulum (increased acetabular tilt) was associated with increased acetabular anteversion and with decreased anterior and anterosuperior acetabular coverage. No correlation was found in controls. In dysplastic hips with a posterior acetabular deficiency, the acetabulum was rotated anteriorly (decreased acetabular tilt) compared with hips with anterior and lateral deficiencies. We observed a correlation between the rotational position of the acetabulum in the pelvis with acetabular version and coverage in hip dysplasia. Our observations confirmed anterior rotation of the acetabular fragment during periacetabular osteotomies is an anatomically reasonable maneuver for hips with anterolateral acetabular deficiencies, while the maneuver can exacerbate posterior coverage and should be avoided in hips with a posterior acetabular deficiency. Level IV, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.


The Bioethicist Who Cried "Synthetic Biology": An Analysis of the Function of Bioterrorism Predictions in Bioethics.
This article analyzes a specter that has haunted bioethics almost since its inception, namely the specter of the misuse of biotechnology by maleficent agents bent on mass destruction, or the complete eradication of human kind and life as we know it. The article provides a general account of why bioethicists cry "catastrophic bioterrorism potential" when new biotechnologies emerge, and an analysis of the arguments that flow from the prediction, especially in relation to synthetic biology.


Assessment of the Utility of the Oral Fluid and Plasma Proteomes for Hydrocodone Exposure.
Non-medical use and abuse of prescription opioids is a growing problem in both the civilian and military communities, with minimal technologies for detecting hydrocodone use. This study explored the proteomic changes that occur in the oral fluid and blood plasma following controlled hydrocodone administration in 20 subjects. The global proteomic profile was determined for samples taken at four time points per subject: pre-exposure and 4, 6, or 168 hours post-exposure. The oral fluid samples analyzed herein provided greater differentiation between baseline and response time points than was observed with blood plasma, at least partially due to significant person-to-person relative variability in the plasma proteome. A total of 399 proteins were identified from oral fluid samples, and the abundance of 118 of those proteins was determined to be significantly different upon metabolism of hydrocodone (4 and 6 hour time points) as compared to baseline levels in the oral fluid (pre-dose and 168 hours). We present an assessment of the oral fluid and plasma proteome following hydrocodone administration, which demonstrates the potential of oral fluid as a noninvasive sample that may reveal features of hydrocodone in opioid use, and with additional study, may be useful for other opioids and in settings of misuse.


A multicentre study to implement nutritional risk screening and evaluate clinical outcome and quality of life in patients with cancer.
To implement nutritional risk screening and evaluate the relationship of nutritional risk to complication rate and quality of life in patients with cancer. A total of 687 patients with cancer from two teaching hospitals in China were consecutively enrolled. Data were collected on the nutritional risk screening, application of nutritional support, complication and quality of life. The prevalence of nutritional risk at admission among the total, younger and elderly patients was 45.6%, 38.7% and 58.0%, respectively. There was a significant increase in the prevalence from admission to 2 weeks after admission in all patients (P=0.011). The prevalence in those patients ≥70 years was significantly higher than that in the younger ones (P<0.001). The highest prevalence of nutritional risk was in pancreas cancer (81.8%). Only 46.7% of at-risk patients received nutritional support and the average PN:EN ratio was 7.0:1. Complications were noted in 29.0% of all patients and were significantly more frequent in 'at-risk' patients (P<0.001). Among the scales of quality of life (SF-36), the scores of physical functioning (P<0.001), role-physical (P<0.001), bodily pain (P=0.012), energy/fatigue (P<0.001) and general health (P<0.001) were significant lower in the patients at risk. A large proportion of cancer inpatients were at nutritional risk and tended to worsen during the course of admission, which has been associated with increased complication rate and lower scores of quality of life. The application of PN and EN was inappropriate in patients with cancer in China.


Helping the Helpers - A research protocol for user-centered technology to aid caregiver management of medications for people with Alzheimer's disease and related dementias.
Systematically supporting caregiver-assisted medication management through IT interventions is a critical area of need toward improving outcomes for people living with ADRD and their caregivers, but a significant gap exists in the evidence base from which IT interventions to support caregivers' medication tasks can be built. User-centered design can address the user needs evidence gap and provide a scientific mechanism for developing IT interventions that meet caregivers' needs. The present study employs the three phases of user-centered design to address the first two stages of the NIH Stage Model for Behavioral Intervention Development. We will conduct a three-phase study employing user-centered design techniques across three aims: Aim 1) assess the needs of ADRD caregivers who manage medications for people with ADRD (Stage 0); Aim 2) co-design a prototype IT intervention to support caregiver-assisted medication management collaboratively with ADRD caregivers (Stage IA); and Aim 3) feasibility test the prototype IT intervention with ADRD caregivers (Stage IB). Our user-centered design protocol provides a template for integrating the three phases of user-centered design to address the first two stages of the NIH Stage Model that can be used broadly by researchers who are developing IT interventions for ADRD caregivers.


A systematic review and meta-analysis of the correlation between maternal and neonatal iron status and haematologic indices.
Iron deficiency (ID) is the leading single-nutrient deficiency in the world. Anaemia is a common outcome of ID that affects half of pregnancies worldwide with serious consequences for child development. Whether haematologic indices and biomarkers of iron status in pregnant women correlate with those of their neonates is unclear. This systematic review evaluated studies comparing haematologic and iron status indices in pregnant women and their newborns/neonates. We searched MEDLINE, EMBASE, CINAHL, and Web of Science from database inception until March 2020 for primary studies comparing haematologic and iron status indices between women and their newborns up to 48 h after birth. We summarized the results descriptively and calculated pooled correlation coefficients in mothers and newborns/neonates using the Schmidt-Hunter method. The protocol was registered at PROSPERO International Prospective Register of Systematic Reviews (Registration number: CRD42018093094). Sixty-five studies were included. Pooled correlation coefficients for biomarkers of iron status in mothers and newborns/neonates were 0.13 (ferritin), 0.42 (hepcidin), 0.30 (serum/plasma iron), 0.09 (transferrin), 0.20 (transferrin saturation), and 0.16 (total iron binding capacity). Pooled correlation coefficients for haematological indices in mothers and newborns/neonates were 0.15 (haemoglobin), 0.15 (haematocrit), 0.25 (mean cell/corpuscular haemoglobin), 0.22 (mean cell/corpuscular volume). Maternal biomarkers of iron and haematologic status correlate poorly with those in newborns/neonates. These results underscore a need for alternative approaches to estimate foetal/neonatal iron status and haematological indices. MBO and SLB hold Canada Research Chairs, and grants from the Women and Children's Health Research Institute and Canadian Institutes of Health Research.


Nursing care by telehealth: what is the influence of distance on communication?
Evaluate the perception of nurses regarding interpersonal communication while providing care via telehealth. Qualitative research realized with seven nurses working in telehealth in Brazil, the sample was determined by data saturation. A questionnaire with open questions was applied and then content analysis of the dialogues was conducted, focusing on thematic analysis. Four categories emerged from the dialogues: Understanding the importance of communication; the interpersonal relationship interfering with communication; Communicating via technology; and Learning the communication process. The perception of nurses working in telehealth in Brazil is that technology has facilitated their professional practice; however, in relation to the communication process, they believe it is harder to communicate by telehealth, mainly due to difficulty in perceiving nonverbal signals. To overcome these difficulties, they agreed that interpersonal communication is a skill that must be acquired during their professional training. Avaliar a percepção do enfermeiro referente à Comunicação interpessoal no cuidado por telessaúde. Pesquisa qualitativa, realizada com sete enfermeiros que atuam em telessaúde no Brasil, com amostra determinada pela saturação de dados. Aplicou-se um questionário com perguntas abertas e foi realizada análise de conteúdo dos discursos, com enfoque na análise temática. Dos discursos emergiram quatro categorias: Entendendo a importância da comunicação; O relacionamento interpessoal interferindo na comunicação; Comunicando-se por meio da tecnologia; e Aprendendo o processo de comunicação. A percepção dos enfermeiros que atuam em telessaúde no Brasil é de que a tecnologia tem facilitado sua prática profissional; porém, em relação ao processo de comunicação, creem que seja mais difícil se comunicar pela telessaúde, principalmente devido à dificuldade de percepção de sinais não verbais. Para superar essas dificuldades, concordam que comunicação interpessoal é uma competência que deve ser adquirida em sua formação profissional.


Advances in the surgical treatment of atrial fibrillation.
There has been a resurgence in the surgical treatment of AF. Although the Maze procedure is extremely effective at curing AF, new surgical approaches are far simpler and include pulmonary vein isolation, left atrial lesions, and excision of the left atrial appendage. Currently applied as an adjunct to other cardiac operations, these new approaches are being modified for thoracoscopic, minimally invasive, epicardial AF ablation. This minimally invasive procedure will enable rapid and effective cure of AF in large numbers of patients.


Fulminant septicemia of Bacillus cereus resistant to carbapenem in a patient with biphenotypic acute leukemia.
We report a case of fulminant septicemia with Bacillus cereus resistant to carbapenem. A 33-year-old man was suffering from febrile neutropenia (FN) on day 15 after the start of remission-induction therapy for biphenotypic acute leukemia under gut decontamination with polymyxin B and nystatin. Meropenem, a carbapenem, was administered according to the guideline for FN. Two days later (on day 17), he complained of severe abdominal pain, lost consciousness, went into sudden cardiopulmonary arrest, and died. Autopsy showed multiple spots of hemorrhage and necrosis caused by bacterial plaque in the brain, lungs, and liver. B. cereus was isolated from a blood sample obtained in the morning on day 17 and it was after his death that the isolated B. cereus was revealed to be resistant to carbapenem. B. cereus obtained from blood samples has been reported to be usually sensitive to carbapenem and also to vancomycin, new quinolones, and clindamycin. If B. cereus resistant to carbapem increases, our method of gut decontamination with polymyxin B and nystatin may have to be changed to one containing a new quinolone for the prevention of septicemia. Careful watching to determine whether B. cereus resistant to carbapem increases may be also important for empiric therapy, because carbapenem is often selected as the initial therapy for FN in patients with severe neutropenia.


Epidemiological situation of leprosy in a province in China: a long time to diagnosis and a high rate of deformity.
This epidemiological study aimed to analyse both the distribution and characteristics of leprosy in an endemic province in Northwest China. The medical records of leprosy patients in the province of Shaanxi, China, from 1998 to 2018 were collected from the Chinese Leprosy Management Information System (LEPMIS). Epidemiological variables were analysed in this study. A total of 477 new cases were diagnosed between 1998 and 2018 in this region. The average annual detection rate was 0.070/100,000 population, and the average annual prevalence was 0.305/100,000 population. The mean age of the newly diagnosed patients was 46.7 years, and the ratio of males to females was 2.5:1. There were 399 cases (83.6%) of multibacillary (MB) leprosy. One hundred forty-eight patients (31.0%) had grade 2 disability. The mean diagnosis time for new cases was 62.0 months. This epidemiological study showed that the characteristics of newly diagnosed leprosy cases in our province were a long time to diagnosis and a high rate of deformity, indicating the need for actions focusing on early diagnosis and treatment and strengthening the detection of leprosy in low-prevalence areas.


Oxidized phospholipids as novel mediators of neurodegeneration.
Neurodegeneration drives the progression of many neurological diseases. Inflammation and oxidative stress occurring in the CNS promote lipid peroxidation, leading to the generation of oxidized phospholipids such as oxidized phosphatidylcholines (OxPCs). OxPCs have been proposed as biomarkers of oxidative stress, where their detection in lesions in multiple sclerosis (MS), frontotemporal lobe dementia, spinal cord injury, and amyotrophic lateral sclerosis (ALS) implies that oxidative insult had occurred. However, recent findings highlight OxPCs as potent neurotoxic species requiring neutralization by microglia. Here, we summarize the science of OxPCs, including lessons from non-CNS diseases. We discuss the potential of OxPCs as common drivers of injury across neurological conditions and encourage investigations of OxPCs as novel neurotoxins.


Kinetic transport model for cellular regulation of pH and solute concentration in the renal proximal tubule.
An open circuit kinetic model was developed to calculate the time course of proximal tubule cell pH, solute concentrations, and volume in response to induced perturbations in luminal or peritubular fluid composition. Solute fluxes were calculated from electrokinetic equations containing terms for known carrier saturabilities, allosteric dependences, and ion coupling ratios. Apical and basolateral membrane potentials were determined iteratively from the requirements of cell electroneutrality and equal opposing transcellular and paracellular currents. The model converged to membrane potentials accurate to 0.05% in one to four iterations. Model variables included cell concentrations of Na, K, HCO3, glucose, pH (uniform CO2), volume, and apical and basolateral membrane potentials. The basic model contained passive apical membrane transport of Na/H, Na/glucose, H and K, basolateral transport of Na/3HCO3, K, H, and glucose, and paracellular transport of Na, K, Cl, and HCO3; apical H and basolateral 3Na/2K-ATPases were present. Apical Na/H and basolateral K transport were regulated allosterically by pH. Apical Na/H transport, basolateral Na/3HCO3 transport, and the 3Na/2K-ATPase were saturable. Model parameters were chosen from data in the rat proximal tubule. Model predictions for the magnitude and time course of cell pH, Na, and membrane potential in response to rapid changes in apical and peritubular Na and HCO3 were in excellent agreement with experiment. In addition, the model requires that there exist an apical H-ATPase, basolateral Na/3HCO3 transport saturable with HCO3, and electroneutral basolateral K transport.


Synthesis of 2-methoxybenzoylhydrazone and evaluation of their antileishmanial activity.
Compounds 1-25 showed varying degree of antileishmanial activities with IC50 values ranging between 1.95 and 88.56 μM. Compounds 2, 10, and 11 (IC50=3.29±0.07 μM, 1.95±0.04 μM, and 2.49±0.03 μM, respectively) were found to be more active than standard pentamidine (IC50=5.09±0.04 μM). Compounds 7 (IC50=7.64±0.1 μM), 8 (IC50=13.17±0.46 μM), 18 (IC50=13.15±0.02 μM), and 24 (IC50=15.65±0.41 μM) exhibited good activities. Compounds 1, 3, 4, 5, 9, 12, 15, 18, and 19 were found to be moderately active. Compounds 13, 14, 16, 17, 20-25 showed weak activities with IC50 values ranging between 57 and 88 μM.


Outcome and prognostic factors in soft tissue sarcoma in the adult.
To evaluate the outcome, patterns of failure and prognostic factors in this rare disease in adult patients treated at a single institution in the modern era. The records of all patients (389 cases) with soft tissue sarcoma in the extremities, torso (excluding retroperitoneum), and head and neck managed between 1980 and 1988 were reviewed. A curative (radical) approach was used in 321 patients of whom 10% were recurrent lesions. The local management consisted of surgery alone in 54 cases, surgery and radiotherapy in 250 and radiotherapy alone in 17. Adjuvant chemotherapy was used as a policy for high grade lesions in the initial five years of the study (98 cases), but was omitted subsequently. Extremity lesions fared more favourably compared to head and neck and torso lesions (p = 0.02) with respect to survival. Extremity and torso lesions had significantly better local control (p < 0.0001) than in the head and neck where local failure was a common cause of death. A multiple Cox regression analysis revealed that resection margins, local extension of tumor, age at diagnosis, and grade correlated with local relapse and distant relapse was also associated with local extension, high grade and in addition, large lesions. Size appeared especially predictive for distant failure, the most common cause of death. Distant failure was not influenced by the use of adjuvant chemotherapy. Patients treated for recurrence in this series had significantly worse survival due to increased distant failure despite similar local control to primary cases. This series highlights the overall problem of distant failure in this disease. It also reaffirms the importance of obtaining local control both in the head and neck, where uncontrolled local disease is the major cause of death, and in general since local relapse appears to increase the risk of distant failure. It appears that the current staging systems should be reviewed in the light of the apparent effect of different prognostic factors.


Intra-ventricular resynchronization for optimal left ventricular function during pacing in experimental left bundle branch block.
We sought to investigate to what extent intra-ventricular asynchrony (intraVA) and inter-ventricular asynchrony (interVA) determine left ventricular (LV) function in canine hearts with left bundle branch block (LBBB) during ventricular pacing. Pacing therapy improves LV pump function in patients with heart failure and abnormal ventricular conduction supposedly due to resynchronization. However, the relationship between LV pump function and measures of asynchrony is not well established. In 15 experiments, LV (various sites) and biventricular (BiV) pacing was performed at atrioventricular (AV) delays of 20 to 140 ms. Measured were the maximum rate of increase (dP/dt(max)) of LV pressure and LV stroke work (SW) (conductance catheter), interVA (time delay between the upslope of LV and RV pressures), and intraVA (from endocardial electrical activation maps). Induction of LBBB increased interVA (-6.4 +/- 8.6 to -28.4 +/- 8.5 ms [RV earlier]) and intraVA (4.9 +/- 2.4 to 18.0 +/- 3.3 ms), whereas LV dP/dt(max) and SW decreased (-13 +/- 18% and -39 +/- 24%, respectively). During LBBB, LV and BiV pacing increased LV dP/dt(max) and SW (mean increases 14% to 21% and 11% to 15%, respectively) without changing diastolic function or preload. Optimal improvement in LV function was obtained consistently when intraVA returned to pre-LBBB values, while interVA remained elevated. Normalization of intraVA required AV delays shorter than the baseline PQ time during LV apex and BiV pacing, thus excluding endogenous LV activation, but AV delays virtually equal to the baseline PQ time (difference 4 +/- 9 ms, p = NS) during pacing at (mid)lateral LV sites to obtain fusion between pacing-induced and endogenous activation. In LBBB hearts, optimal restoration of LV systolic function by pacing requires intra-ventricular resynchronization. The optimal AV delay to achieve this depends on both the site of pacing and baseline PQ time.


Near-infrared spectroscopy: applications in neonates.
Near-infrared spectroscopy (NIRS) offers non-invasive, in-vivo, real-time monitoring of tissue oxygenation. Changes in regional tissue oxygenation as detected by NIRS may reflect the delicate balance between oxygen delivery and consumption. Originally used predominantly to assess cerebral oxygenation and perfusion perioperatively during cardiac and neurosurgery, and following head trauma, NIRS has gained widespread popularity in many clinical settings in all age groups including neonates. However, more studies are required to establish the ability of NIRS monitoring to improve patient outcomes, especially in neonates. This review provides a comprehensive description of the use of NIRS in neonates.


Chemotherapy for diffuse low-grade gliomas in adults.
Diffuse low-grade gliomas (LGGs) in adults are progressive brain tumours that are radiologically characterized by slow and continuous growth that precedes anaplastic transformation. Standard treatment includes surgery and radiotherapy though the optimal timing of radiotherapy remains unsettled. Several retrospective and phase II studies have demonstrated that chemotherapy is also an interesting treatment option. However, several questions remain unanswered regarding its optimal use. The present review focuses on past, recent and ongoing developments in LGGs chemotherapy, including response assessment and potential predictive biomarkers of chemosensitivity.


Regional lung function following hip arthroplasty and preoperative normovolemic hemodilution.
The effect of preoperative normovolemic hemodilution with dextran 70 as dilutional agent on postoperative regional lung function was evaluated in patients undergoing hip arthroplasty in the lateral decubitus position. The major part of the surgical blood loss of these patients was replaced with the received autologous blood. The results obtained were compared to changes in a group of patients in whom the operative bleeding was replaced with bank blood. Regional lung function, as studied with Xe133 radiospirometry, is not negatively influenced by the hemodilution technique. In both groups a reduction in perfusion, ventilation and volume of ventilated alveoli was revealed postoperatively in the lung that was dependent during surgery, probably caused by impaired ventilation of this lung and peroperatively induced microembolism. A more rapid normalization was found in the preoperatively hemodiluted patients. The reduced volume of bank blood transfused to these patients and/or a protective effect of the preoperatively infused dextran on the microembolism evoked by the surgical trauma might explain this difference between the groups studied.


Relentless pulmonary vein stenosis after repair of total anomalous pulmonary venous drainage.
Progressive stenosis of the pulmonary veins after repair of total anomalous pulmonary venous drainage is frequently refractory to surgical therapy. Retrospective review of 170 consecutive patients treated for total anomalous pulmonary venous drainage identified 13 patients with postrepair pulmonary vein stenosis. Preoperative and operative data were analyzed to define the patterns of progression and efficacy of surgical techniques. Seventeen reoperations were performed in 13 patients. Postrepair pulmonary vein stenosis was most common in the infracardiac and mixed subtypes (p < 0.02). All 4 patients with unilateral stenosis, 2 of whom had progression of stenosis resulting in nearly complete unilateral pulmonary vein occlusion, survived. Six of 9 patients with bilateral disease died (p < 0.05 versus unilateral); 2 of the 3 survivors were repaired with a novel technique creating a sutureless neoatrium without evidence of restenosis at 1.8 years' follow-up. Stenting was uniformly unsuccessful. In unilateral stenosis, progression of disease may be survivable with loss of single-lung perfusion. Although bilateral disease is lethal in most cases, creation of a sutureless neoatrium has demonstrated short-term freedom from disease progression.


ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation.
Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention, but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP-signaling-disabled R-spondin (RSPO) chimeras, which leverage the specificity of these stem cell growth factors for ZNRF3/RNF43 E3 transmembrane ligases, to target degradation of transmembrane proteins. As a proof-of-concept, we targeted the immune checkpoint protein, programmed death ligand 1 (PD-L1), a prominent cancer therapeutic target, with a bispecific RSPO2 chimera, R2PD1. The R2PD1 chimeric protein binds to PD-L1 and at picomolar concentration induces its lysosomal degradation. In three melanoma cell lines, R2PD1 induced between 50 and 90% PD-L1 protein degradation. PD-L1 degradation was strictly dependent on ZNRF3/RNF43. Moreover, R2PD1 reactivates cytotoxic T cells and inhibits tumor cell proliferation more potently than Atezolizumab. We suggest that signaling-disabled ROTACs represent a paradigm to target cell surface proteins for degradation in a range of applications.


Nicotinamide adenine dinucleotide glycohydrolase from rat liver nuclei. Isolation and characterization of a new enzyme.
A new type of nicotinamide adenine dinucleotide glycohydrolase (NADase) has been isolated from rat liver nuclei. When partially purified chromatin is passed through a Sephadex G-200 column in the presence of 1 M NaCl, enzyme activities catalyzing the liberation of nicotinamide from NAD elute in two peaks. One, which appears in the void volume fraction, hydrolyzes the nicotinamide-ribose linkage of NAD to produce nicotinamide and ADP-ribose in stoichiometric amounts. This activity is not inhibited by 5 mM nicotinamide. The other, which elutes much later, catalyzes the formation of poly(ADP-ribose) from NAD and is completely inhibited by 5 mM nicotinamide. The former, NADase, is DNase-insensitive and thermostable, has a pH optimum of 6.5 to 7, a Km for NAD of 28 muM, and a Ki for nicotinamide of 80 mM, and hydrolyzes NADP as well as NAD. The latter, poly(ADP-ribose) synthetase, is sensitive to DNase treatment and heat labile, has a pH optimum of 8 to 8.5, a Km for NAD of 250 muM and a Ki for nicotinamide of 0.5 mM and is strictly specific for NAD. Further, the former NADase is shown to lack transglycosidase activity, which has been documented to be a general property of NADases derived from animal tissues. These results indicate that the NAD-hydrolyzing enzyme newly isolated from nuclei is a novel type of mammalian NADase which catalyzes the hydrolytic cleavage of the nicotinamide-ribose linkage of NAD.


Mechanisms of toxic injury to isolated hepatocytes by 1-naphthol.
The mechanism(s) of toxicity of 1-naphthol and two of its possible metabolites, 1,2- and 1,4-naphthoquinone, to freshly isolated rat hepatocytes has been studied. 1-Naphthol and both naphthoquinones exhibited a dose-dependent toxicity to hepatocytes. [1-14C]-1-Naphthol was metabolised by hepatocytes predominantly to its glucuronic acid and sulphate ester conjugates, but small amounts of covalently bound products were also formed. Blebbing on the surface of the hepatocytes was observed following exposure to 1-naphthol and the naphthoquinones, together with a dose-dependent decrease in intracellular glutathione (GSH), which preceded the onset of cytotoxicity. The toxicity of 1-naphthol and the naphthoquinones was potentiated by dicoumarol, an inhibitor of DT-diaphorase (NAD(P)H:quinone oxidoreductase). This enhanced toxicity was accompanied by a greater amount of surface blebbing, an increased depletion of intracellular GSH, particularly in the case of 1-naphthol and 1,4-naphthoquinone, and a decreased metabolism of 1-naphthol to its conjugates with variable effects on the amount of covalently bound products formed. These results support the suggestion that the toxicity of 1-naphthol may be mediated by the formation of 1,2-naphthoquinone and/or 1,4-naphthoquinone, which may then be metabolised by one electron reduction to naphthosemiquinone radicals. These, in turn, may covalently bind to important cellular macromolecules or enter a redox cycle with molecular oxygen thereby generating active oxygen species. Both of these processes appear to play a role in producing the cytotoxic effects of 1-naphthol.


Enhanced dibenzothiophene biodesulfurization in a microchannel reactor.
A microchannel reactor system was used in a biodesulfurization process in which the rate of biodesulfurization in the oil/water phase of the microchannel reaction was more than nine-fold that in a batch (control) reaction. In addition, the microchannel reaction system using a bacterial cell suspension degraded alkylated dibenzothiophene that was not degraded by the batch reaction system. This work provides a foundation for the application of a microchannel reactor system consisting of biological catalysts using an oil/water phase reaction.


The roles of adult and larval specialisations in limiting the occurrence of five species of Dacus (Diptera: tephritidae) in cultivated fruits.
The relative importance of adult preferences or specialisations of larval physiology in restricting the host range of five species of Dacine fruit flies (Diptera: Tephritidae) was examined, with particular emphasis on their utilization of cultivated fruits. The species; D. tryoni, D. jarvisi, D. cucumis, D. musae and D. cacuminatus differ widely in host range with D. tryoni being highly polyphagous while D. cacuminatus is virtually monophagous. Laboratory experiments showed that larvae of all species survived and developed in many cultivated fruits in which the specialists never occur in the field. By contrast the oviposition preferences and specificity of adult females differed widely between species. Female D. tryoni oviposited in most species of fruit. The specialised species; D. cucumis, D. musae and D. cacuminatus strongly preferred their usual hosts and would not oviposit in novel fruits even in the absence of the preferred host. In contrast, D. jarvisi consistently preferred its main native host but when this was not offered readily accepted cultivated fruits. These differences in preference are consistent with the pattern of infestation displayed by each species in the field. The study indicate that, in general, the occurrence of these species of Dacus in cultivated fruits is constrained more by the behavioural preferences of adult females than by larval specialisations. A genetic change in some aspect of host recognition or acceptance would be necessary for the specialised species to regularly infest cultivated fruits though no change in larval characteristics may be needed. As the types and concentrations of defensive secondary compounds may differ between native and cultivated fruits this conclusion cannot be extended to host shifts among native fruits.


Chromosome-level genome assembly of bunching onion illuminates genome evolution and flavor formation in Allium crops.
The Allium genus is cultivated globally as vegetables, condiments, or medicinal plants and is characterized by large genomes and strong pungency. However, the genome evolution and genomic basis underlying their unique flavor formation remain poorly understood. Herein, we report an 11.27-Gb chromosome-scale genome assembly for bunching onion (A. fistulosum). The uneven bursts of long-terminal repeats contribute to diversity in genome constituents, and dispersed duplication events largely account for gene expansion in Allium genomes. The extensive duplication and differentiation of alliinase and lachrymatory factor synthase manifest as important evolutionary events during flavor formation in Allium crops. Furthermore, differential selective preference for flavor-related genes likely lead to the variations in isoalliin content in bunching onions. Moreover, we reveal that China is the origin and domestication center for bunching onions. Our findings provide insights into Allium genome evolution, flavor formation and domestication history and enable future genome-assisted breeding of important traits in these crops.


Asbestos-related pleural diseases: dimensional criteria are not appropriate to differentiate diffuse pleural thickening from pleural plaques.
In the literature, the criteria used to define pleural plaques (PP) and diffuse pleural thickening (DPT) are very heterogeneous and often imprecise. A multicenter restropective study was conducted to assess the relevance of two radiographic definitions of DPT. The study population consisted of 287 subjects with asbestos-related pleural thickening. Two definitions were used to characterize DPT on postero-anterior chest radiographs: definition 1: pleural thickening associated with obliteration of the costophrenic angle; definition 2: pleural thickening at least 5 mm wide, extending for more than one quarter of the chest wall. Prevalence of respiratory symptoms and pulmonary function tests were compared in the DPT and PP groups resulting from the two definitions of DPT. According to definition 1, 34 patients (11.8%) were classified in the DPT group. Prevalence of chronic sputum, dyspnea, and chest pain was significantly higher in this group than in the PP group. FEV(1), FVC, and TLC were significantly lower. The differences persisted after adjustment for confounding factors. According to definition 2,102 patients (36.6%) were classified in the DPT group. DPT and PP groups did not differ in terms of prevalence of respiratory symptoms, or pulmonary function tests. Agreement between readers was significantly better when using definition 1. Obliteration of costophrenic angle is a much more reliable sign than dimensional criteria to characterize DPT.


MALDI Mass Spectrometry Imaging in a Primary Demyelination Model of Murine Spinal Cord.
Destruction of myelin, or demyelination, is a characteristic of traumatic spinal cord injury and pathognomonic for primary demyelinating pathologies such as multiple sclerosis (MS). The regenerative process known as remyelination, which can occur following demyelination, fails as MS progresses. Models of focal demyelination by local injection of gliotoxins have provided important biological insights into the demyelination/remyelination process. Here, injection of lysolecithin to induce spinal cord demyelination is investigated using matrix-assisted laser desorption/ionization mass spectrometry imaging. A segmentation analysis revealed changes to the lipid composition during lysolecithin-induced demyelination at the lesion site and subsequent remyelination over time. The results of this study can be utilized to identify potential myelin-repair mechanisms and in the design of therapeutic strategies to enhance myelin repair.


Structural racism and geographic access to food retailers in the United States: A scoping review.
This scoping review summarized findings and key measures from U.S.-based studies that 1) examined associations between geographic indicators of structural racism (e.g., redlining, racial segregation) and access to food retailers (e.g., supermarkets, convenience stores) or 2) documented disparities in access by neighborhood racial/ethnic composition. In 2022, relevant scientific literature was reviewed using Covidence software. Independent reviewers examined 13,069 citations; 163 citations advanced to the full-text review stage and 70 were selected for inclusion. Twenty-one studies (30%) linked one or more indicator of structural racism to food retailer access while 49 (70%) solely examined differences in access by neighborhood racial/ethnic composition. All studies featuring indicators of structural racism reported significant findings; however, indicators varied across studies making it difficult to make direct comparisons. Key indicators of structural racism in the food access literature included redlining (n = 3), gentrification (n = 3), and racial segregation (n = 4). Many U.S.-based studies have evaluated food retailer access by neighborhood racial/ethnic composition. Moving forward, studies should model indicators of structural racism and determine their influence on geographic access to large and small food retailers.


Partitioning of Chemotherapeutics into Nuclear Condensates-Opening the Door to New Approaches for Drug Development.
Klein et al. (2020) demonstrate for the first time that small-molecule cancer therapeutics are selectively partitioned and concentrated within phase-separated nuclear condensates, providing new insights to drug efficacy and creating the opportunity for enhanced control of therapeutic targeting.


Coping with Coronavirus Pandemic: Risk Perception Predicts Life Optimism.
Given that the coronavirus pandemic has become a severe concern worldwide, how can optimism be maintained during an outbreak of a collective pandemic? We propose that perceived control and negative affect could be potential explanatory factors for optimism in the face of a pandemic. In Study 1 (N = 599), through a large-scale cross-sectional design, we showed the indirect effect of risk perception on optimism through perceived control and negative affect with structural equation modeling. In Study 2 (N = 191), we manipulated perceived risk of the pandemic and determined that experiencing a high-risk pandemic psychologically led to decreased optimism. Finally, through Study 3 (N = 186) and Study 4 (N = 217), we revealed that the effect of risk perception on optimism can be extended to overall subjective well-being and confirmed the indirect effects via perceived control and negative affect. These findings indicate that risk perception can make a difference in one's life optimism during a high-risk pandemic. Moreover, perceived control and negative affect are notable intermediary variables. Measures that strengthen publicity and transparency regarding recovery rates should be taken to help reduce public perceptions of risk and promote an optimistic life attitude.


Polymorphism and parent-of-origin effects on gene expression of CAST, leptin and DGAT1 in cattle.
This study aimed to investigate differential allele expression (DAE) and polymorphism and parent-of-origin effects on expression of genes related to beef traits. CAST, related to meat tenderness, and DGAT1 and leptin, related to fat deposition, were evaluated. In bovine fetal tissues CAST was expressed twice as much (P < 0.05) in muscle of homozygous GG than in heterozygous AG. Leptin was expressed about one-tenth as much (P < 0.05) in heterozygous TpCm (allele T of paternal origin and allele C of maternal origin) than in homozygous CC. No DAE was observed. The evidence of polymorphism effect on expression of CAST and parent-of-origin effect on leptin contributes to a better understanding of events controlling the expression of genes of economic interest in cattle. Furthermore, if the parent-of-origin effects observed in fetal tissues are confirmed in adult tissues and associated to phenotypic variation, this parental origin criterion may be considered in marker-assisted selection of beef traits.


Lymph node tuberculosis: a comparison of treatments 18 months after completion of chemotherapy.
Ninety patients with lymph node tuberculosis were treated with either rifampicin and isoniazid or ethambutol and isoniazid for 18 months, supplemented by sheptomycin for the first two months. No differences emerged between the two regimens, either during treatment or during an 18 month post-chemotherapy follow-up. In 7% of patients lymph nodes enlarged transiently after the end of treatment and in 7% enlarged nodes persisted. No patient required further treatment. One patient was left with an intermittently discharging sinus in an operation scar.


[Practical determination of volume and doses in conformal radiotherapy].
The determination of the target volumes and the dose to be delivered are critical medical steps in order to locally control the disease and to limit the risks of normal tissues injury. While many clinical situations are compatible with standardised technique and beam arrangements, the tools provided by modern medical diagnostic imaging procedures and tridimensional dosimetry allow an improved conformation of the irradiated volume and the administered dose to the clinical target volume. However, this approach requires an increased precision in tumour and normal tissues delineation, based on patient immobilisation devices, standardisation of mobile organs repletion status and image acquisition procedures, explicit definition of the biological and physical safety margins, definition of acceptable levels of dose heterogeneity in the planning target volume and appropriate quality assurance procedures.


On complexity and homogeneity measures in predicting biological aggressiveness of prostate cancer; Implication of the cellular automata model of tumor growth.
We propose a novel approach for the quantitative evaluation of aggressiveness in prostate carcinomas. The spatial distribution of cancer cell nuclei was characterized by the global spatial fractal dimensions D0, D1, and D2. Two hundred eighteen prostate carcinomas were stratified into the classes of equivalence using results of ROC analysis. A simulation of the cellular automata mix defined a theoretical frame for a specific geometric representation of the cell nuclei distribution called a local structure correlation diagram (LSCD). The LSCD and dispersion Hd were computed for each carcinoma. Data mining generated some quantitative criteria describing tumor aggressiveness. Alterations in tumor architecture along progression were associated with some changes in both shape and the quantitative characteristics of the LSCD consistent with those in the automata mix model. Low-grade prostate carcinomas with low complexity and very low biological aggressiveness are defined by the condition D0 < 1.545 and Hd < 38. High-grade carcinomas with high complexity and very high biological aggressiveness are defined by the condition D0 > 1.764 and Hd < 38. The novel homogeneity measure Hd identifies carcinomas with very low aggressiveness within the class of complexity C1 or carcinomas with very high aggressiveness in the class C7.


MiR-590-3p regulates proliferation, migration and collagen synthesis of cardiac fibroblast by targeting ZEB1.
Previous studies have implicated the attractive and promising role of miR-590-3p to restore the cardiac function following myocardial infarction (MI). However, the molecular mechanisms for how miR-590-3p involves in cardiac fibrosis remain largely unexplored. Using human cardiac fibroblasts (HCFs) as the cellular model, luciferase report assay, mutation, EdU assay and transwell migration assay were applied to investigate the biological effects of miR-590-3p on the proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts. We found that miR-590-3p significantly suppressed cell proliferation and migration of HCFs. The mRNA and protein expression levels of α-SMA, Col1A1 and Col3A were significantly decreased by miR-590-3p. Moreover, miR-590-3p directly targeted at the 3'UTR of ZEB1 to repress the translation of ZEB1. Interfering with the expression of ZEB1 significantly decreased the cell proliferation, migration activity, mRNA and protein expressions of α-SMA, Col1A1 and Col3A. Furthermore, the expressions of miR-590-3p and ZEB1 were identified in infarct area of MI model in pigs. Collectively, miR-590-3p suppresses the cell proliferation, differentiation, migration and collagen synthesis of cardiac fibroblasts by targeting ZEB1. These works will provide useful biological information for future studies on potential roles of miR-590-3p as the therapeutic target to recover cardiac function following MI.


Disparities in postoperative opioid prescribing by race and ethnicity: an electronic health records-based observational study from Northern California, 2015-2020.
To examine racial and ethnic disparities in postoperative opioid prescribing. Electronic health records (EHR) data across 24 hospitals from a healthcare delivery system in Northern California from January 1, 2015 to February 2, 2020 (study period). Cross-sectional, secondary data analyses were conducted to examine differences by race and ethnicity in opioid prescribing, measured as morphine milligram equivalents (MME), among patients who underwent select, but commonly performed, surgical procedures. Linear regression models included adjustment for factors that would likely influence prescribing decisions and race and ethnicity-specific propensity weights. Opioid prescribing, overall and by race and ethnicity, was also compared to postoperative opioid guidelines. Data were extracted from the EHR on adult patients undergoing a procedure during the study period, discharged to home with an opioid prescription. Among 61,564 patients, on adjusted regression analysis, non-Hispanic Black (NHB) patients received prescriptions with higher mean MME than non-Hispanic white (NHW) patients (+ 6.4% [95% confidence interval: 4.4%, 8.3%]), whereas Hispanic and non-Hispanic Asian patients received lower mean MME (-4.2% [-5.1%, -3.2%] and - 3.6% [-4.8%, -2.3%], respectively). Nevertheless, 72.8% of all patients received prescriptions above guidelines, ranging from 71.0 to 80.3% by race and ethnicity. Disparities in prescribing were eliminated among Hispanic and NHB patients versus NHW patients when prescriptions were written within guideline recommendations. Racial and ethnic disparities in opioid prescribing exist in the postoperative setting, yet all groups received prescriptions above guideline recommendations. Policies encouraging guideline-based prescribing may reduce disparities and overall excess prescribing.


Role of Cardiac Myocytes Heart Fatty Acid Binding Protein Depletion (H-FABP) in Early Myocardial Infarction in Human Heart (Autopsy Study).
Many immunohistochemical markers have been used in the postmortem detection of early myocardial infarction. In the present study we examined the role of Heart-type fatty acid binding protein (H-FABP), in the detection of early myocardial infarction. We obtained samples from 40 human autopsy hearts with/without histopathological signs of ischemia. All cases of definite and probable myocardial infarction showed a well-defined area of H-FABP depletion. All of the control cases showed strong H-FABP expression, except two markedly autolysed myocardial samples that showed affected antigenicity. Thus, we suggest H-FABP as being one of the valuable tools facing the problem of postmortem detection of early myocardial infarction/ischemia, but not in autolysis.


An unusual cause of recurrent syncope in a patient with implantable cardioverter defibrillator.
Electromagnetic interferences (EMI) deriving from electrical devices may affect implantable cardioverter defibrillators (ICD). Improved algorithms have been developed in order to minimize adverse effects. However, caution should be still recommended in ICD recipients when handling electrical devices. Here we describe the case of an ICD patient with recurrent syncopal episodes due to inhibition of pacing by oversensing of electrical noise from a not properly grounded washing machine.


Predator-prey-subsidy population dynamics on stepping-stone domains.
Predator-prey-subsidy dynamics on stepping-stone domains are examined using a variety of network configurations. Our problem is motivated by the interactions between arctic foxes (predator) and lemmings (prey) in the presence of seal carrion (subsidy) provided by polar bears. We use the n-Patch Model, which considers space explicitly as a "Stepping Stone" system. We consider the role that the carrying capacity, predator migration rate, input subsidy rate, predator mortality rate, and proportion of predators surviving migration play in the predator-prey-subsidy population dynamics. We find that for certain types of networks, added mobility will help predator populations, allowing them to survive or coexist when they would otherwise go extinct if confined to one location, while in other situations (such as when sparsely distributed nodes in the network have few resources available) the added mobility will hurt the predator population. We also find that a combination of favourable conditions for the prey and subsidy can lead to the formation of limit cycles (boom and bust dynamic) from stable equilibrium states. These modifications to the dynamics vary depending on the specific network structure employed, highlighting the fact that network structure can strongly influence the predator-prey-subsidy dynamics in stepping-stone domains.


Exocrine pancreas: difference in the amylase content of the dorsal and ventral regions.
The amylase content of the acinar tissue is higher in the splenic region of the rat pancreas containing glucagon-rich islets than in the duodenal region harboring pancreatic polypeptide-rich islets.


Influence of the age of algae fed to rotifers (Brachionus plicatilis O.F. Müller) on the expression of mixis in their progenies.
The sequence of the appearance of mixis in the rotifer Brachionus plicatilis was followed among the descendents of amictic rotifers transferred from a high salinity media (40 S) to a low one (9 S). All the neonates that hatched from the amictic eggs, after being transferred to a low salinity, were amictic. Each one of these neonates was cultured individually and its offspring removed periodically every 8-10 h. It was observed that throughout their reproductive phase, these parental females retained their potential to produce either mictic or amictic offspring. All the first produced neonates developed into amictic females, but among those produced later, three patterns were prevalent. The prevalent pattern (type A) was one in which the probability of a neonate being mictic increased towards the middle of the parents' reproductive phase and was followed by a slow decline. In the second pattern (type B), the probability of a daughter being mictic was constant throughout the parents' reproductive phase. It is suspected that the quality of food supplied to the rotifers determines the appearance of patterns, A, B or C. It is postulated that the innate capacity of rotifers to undergo mixis is genetically controlled, while its expression is modulated by environmental conditions.


Dual-energy estimates of volumetric bone mineral densities in the lumbar spine using quantitative computed tomography better correlate with fracture properties when compared to single-energy BMD outcomes.
It is estimated that over 200 million people worldwide are affected by osteoporosis. Vertebral fracture risk prediction using dual energy x-ray absorptiometry (DXA) is confounded by limitations of the technology, such as 2D measurements of bone mineral density (BMD), inability to measure bone distribution and heterogeneity, and potential overestimations of BMD due to degenerative diseases. To overcome these shortcomings, single energy (SE) quantitative computed tomography (QCT) imaging estimates of Hounsfield units (HU) and volumetric BMD have been implemented as alternative methodologies for assessing fracture risk. However, marrow fat within the vertebrae can highly affect the vBMD and fracture properties estimations. To address this issue, 54 vertebrae were dissected from nine cadaveric spines and scanned using SE-QCT (120kVp) and dual energy (DE)-QCT (80/140 kVp), with the latter accounting for marrow fat within the vertebrae. The vertebrae were then scanned using DXA and subjected to mechanical testing to obtain fracture properties. aBMD outcomes from DXA showed a better correlation with DE-QCT vBMD versus SE outcomes [DE: aBMD vs. vBMD (R2: 0.61); SE: aBMD vs. vBMD (R2: 0.27)]. SE-QCT underestimated vertebral vBMD by -56% (p<0.0001) when compared to DE-QCT. vBMD estimates from SE-QCT could predict 45% and 37% of the vertebral failure loads and stiffness, respectively, compared to 67% and 46% from DE-QCT. DE-QCT vBMD outcomes highly correlated with fracture properties of vertebrae as compared to SE-QCT metrics. As DE scanning has the ability to correct for the effects of bone marrow fat, estimated vBMD from SE-QCT were significantly underestimated compared to DE-QCT. Dual energy CT scanning has the potential to more accurately predict vertebral failure and aid the clinician in the evaluation of appropriate interventions. Future studies should consider implementing DE-QCT in their fracture assessment.


Synthesis and characterization of Ag@Cu-based MOFs as efficient adsorbents for iodine anions removal from aqueous solutions.
Due to the critical importance of capturing radioiodine from aquatic environments for human health and ecosystems, developing highly efficient adsorbent materials with rapid kinetics for capturing iodide ions in aqueous solutions is urgently needed. Although extensive research has been conducted on iodine adsorption in gas and organic phases, limited research has been dedicated to adsorption in aqueous solutions. An effective technique for removing iodide was proposed using Ag@Cu-based MOFs synthesized by incorporating Ag into calcined HKUST-1 with varying mass ratios of Ag/Cu-C. Extensive characterization using SEM, XRD, XPS, and nitrogen adsorption-desorption analysis confirmed successful incorporation of Ag in Cu-C. Batch adsorption experiments were conducted, demonstrating that the 5% Ag@Cu-C material exhibited a high adsorption capacity of 247.1 mg g-1 at pH 3. Mechanism investigations revealed that Cu0 and dissolved oxygen in water generate Cu2O and H2O2, while Ag and a small amount of CuO generate Ag2O and Cu2O. Furthermore, iodide ions in the solution are captured by Cu+ and Ag+ adsorption sites. These findings highlighted the potential of Ag@Cu-based MOFs as highly effective adsorbents for iodine anions removal in radioactive wastewater.


Detection of mouse mammary tumor virus RNA in BALB/c tumor cell lines of nonviral etiologies.
A complementary DNA (cDNA) probe to mouse mammary tumor virus (MMTV) RNA was synthesized using calf thymus DNA oligonucleotides as a random primer. This probe was then used to study the expression of MMTV RNA in cell lines from BALB/c tumors induced in vivo either spontaneously or in response to viral, chemical, or hormonal stimuli. The cDNA had a length of approximately 400 to 500 nucleotides and specifically hybridized to MMTV RNA and BALB/c lactating mammary gland RNA, but not to Moloney leukemia virus RNA. Calf thymus DNA-primed cDNA could protect 50% of iodinated MMTV RNA from S1 nuclease digestion at cDNA-RNA ratios of 1:1 and 90% of labeled viral RNA at ratios of 10:1. Thermal denaturation of MMTV RNA-cDNA hybrids yielded a T(m) of 88.5 degrees C, indicative of a well-base-paired duplex. Screening of mouse mammary tumor cells for MMTV sequences revealed that three out of five lines of BALB/c origin had undetectable levels of viral RNA (<three molecules per cell) by RNA excess hybridization. Two of the three "virus-negative" cell lines were derived from tumors induced by the chemical carcinogen 7,12-dimethylbenz(alpha)anthracene, whereas the third tumor occurred spontaneously. Two lines from tumors induced by either viral (mammary tumor virus) or hormonal (17-beta-estradiol) stimulus contained between three and nine molecules of MMTV RNA per cell by both RNA excess and cDNA excess hybridization. Clonal derivatives of these tumor lines had levels of viral RNA comparable to those of their parental lines. Therefore, it appears that the presence of detectable MMTV RNA sequences is not a necessary requirement for the maintenance of all murine mammary gland neoplasias.


Learning from the experts: Evaluating a participatory autism and universal design training for university educators.
Autistic university students have many strengths. They also go through difficulties that professors may not understand. Professors may not understand what college life is like for autistic students. They might judge autistic students. A team of autistic and non-autistic researchers made a training to help professors understand autistic students better. This training also gave professors ideas to help them teach all of their students. Ninety-eight professors did an online survey before the autism training. They shared how they felt about autism and teaching. Before our training, professors who knew more about autism appreciated autism more. Professors who thought people should be equal and women also appreciated autism more. Then, 89 of the professors did our training and another survey after the training. This helped us see what they learned from the training. They did one more survey a month later. This helped us see what they remembered. Our training helped professors understand and value autism. It also helped them understand how they can teach all students better. The professors remembered a lot of what we taught them. This study shows that a training that autistic people helped make can help professors understand their autistic students better.


First record of Acrocercops serrigera serrigera Meyrick (Lepidoptera: Gracillariidae) from Chile.
Acrocercops Wallengren (Gracillariidae) is recorded for the first time from Chile. The little known Acrocercops serrigera serrigera Meyrick is reported from the Azapa Valley, Arica Province, northern Chilean coastal desert. Specimens were reared from Malva nicaeensis and Waltheria ovata (both Malvaceae). Specimen identification is based on comparisons of the male genitalia with that of the lectotype of the species originated from Peru. Sequences of a fragment of the mitochondrial gene cytochrome oxidase subunit I of specimens reared on both plants indicate that there is only one Acrocercops species involved as only one substitution site was found over the 524-bp sequenced.


Estimating the influenza vaccine effectiveness against medically attended influenza in clinical settings: a hospital-based case-control study with a rapid diagnostic test in Japan.
Influenza vaccine effectiveness (VE) studies are usually conducted by specialized agencies and require time and resources. The objective of this study was to estimate the influenza VE against medically attended influenza using a test-negative case-control design with rapid influenza diagnostic tests (RIDT) in a clinical setting. A prospective study was conducted at a community hospital in Nagasaki, western Japan during the 2010/11 influenza season. All outpatients aged 15 years and older with influenza-like illnesses (ILI) who had undergone RIDT were enrolled. A test-negative case-control design was applied to estimate the VEs: the cases were ILI patients with positive RIDT results and the controls were ILI patients with negative RIDT results. Information on patient characteristics, including vaccination histories, was collected using questionnaires and medical records. Between December 2010 and April 2011, 526 ILI patients were tested with RIDT, and 476 were eligible for the analysis. The overall VE estimate against medically attended influenza was 47.6%, after adjusting for the patients' age groups, presence of chronic conditions, month of visit, and smoking and alcohol use. The seasonal influenza vaccine reduced the risk of medically attended influenza by 60.9% for patients less than 50 years of age, but a significant reduction was not observed for patients 50 years of age and older. A sensitivity analysis provided similar figures. The test-negative case-control study using RIDT provided moderate influenza VE consistent with other reports. Utilizing the commonly used RIDT to estimate VE provides rapid assessment of VE; however, it may require validation with more specific endpoint.


Endotoxins in culture medium for human in vitro fertilization.
Endotoxins were detected in a few batches of culture medium during the authors' human in vitro fertilization program. Two distinct levels of endotoxins were assayed: greater than 1 ng/ml and less than 1 ng/ml. The source of endotoxin was traced to culture media obtained from a reputable manufacturing company. The incidence of fertilization per patient was not significantly affected by the presence of endotoxins, but fertilization assessed on the overall number of oocytes was significantly reduced (53%) when endotoxin levels were greater than 1 ng/ml compared with an assay negative for endotoxins (66%) (P = 0.047). The percentage of oocytes cleaving after the observation of two pronuclei was not significantly different, but the degree of fragments observed in the conceptus was significantly more severe if the endotoxin level reached 1 ng/ml. In this investigation, the incidence of pregnancy was 8% when the endotoxin level was greater than 1 ng/ml, 30% if less than 1 ng/ml, and 32% if no endotoxins were detected. This study suggests that, although endotoxins may be present in the culture medium at a deleterious level of at least 1 ng/ml, fertilization and cleavage will be obtained, but there will be a significant increase in the incidence of conceptuses with cytoplasmic fragments; this may result in a reduction in the incidence of pregnancy.


Islet insulin content and release are increased in male mice with elevated endogenous GH and IGF-I, without evidence of systemic insulin resistance or alterations in β-cell mass.
It is clear that elevations in circulating GH can lead to an increase in insulin levels. This increase in insulin may be due to GH-mediated insulin resistance and enhanced lipolysis. However, there is also in vitro and in vivo evidence that GH acts directly to increase β-cell proliferation and insulin production. Our laboratory recently developed an animal model with elevated endogenous GH levels associated with a small (25%), but significant, increase in IGF-I (HiGH mice). As expected, insulin levels were elevated in HiGH mice; however, whole body insulin sensitivity was not altered and glucose tolerance was improved. This metabolic phenotype suggests that modest elevations in circulating GH and IGF-I may enhance β-cell mass and/or function, in the absence of systemic insulin resistance, thus improving glucose homeostasis. To determine if β-cell mass and/or function is altered in HiGH mice. Male HiGH mice and their littermate controls were fed a low-fat or high-fat diet. Body composition and circulating metabolic endpoints were monitored overtime. The pancreas was recovered and processed for assessment of β-cell mass or in vitro basal and glucose-stimulated insulin secretion. HiGH mice showed elevated circulating insulin and normal glucose levels, while non-esterified FFA levels and triglycerides were reduced or normal, depending on diet and age. β-cell mass did not differ between HiGH and control mice, within diet. However, islets from HiGH mice contained and released more insulin under basal conditions, as compared to control islets, while the relative glucose-stimulated insulin release did not differ. Taken together, these results suggest moderate elevations in circulating GH and IGF-I can directly increase basal insulin secretion without impacting β-cell mass, independent of changes in whole body insulin sensitivity and hyperlipidemia.


Characterization, expression and transcriptional regulation of P450c17-I and -II in the medaka, Oryzias latipes.
Recently we reported the isolation of two types of cytochrome P450c17s (steroid 17alpha-hydroxylase/C17, 20 lyase) encoded by two different genes, from genomes of teleost fish. In this study, we characterized the expression profile, enzymatic activity and transcriptional regulation of P450c17-I and -II in the medaka ovary. Similar to tilapia, medaka P450c17-I possessed both hydroxylase and lyase activities, while P450c17-II possessed only the hydroxylase activity. In situ hybridization and gene expression profiles during 48h prior to spawning indicated that P450c17-I is responsible for the production of estradiol-17beta during oocyte growth, while P450c17-II for the production of 17alpha, 20beta-dihydroxy-4-pregnen-3-one during oocyte maturation and cortisol production in the head kidney. Luciferase assays and expression profiles of transcription factors as revealed by real time PCR suggested that P450c17-I and -II expression are tightly controlled by Ad4BP/SF-1, Lrh-1, Foxl2, and Dax1 during the 48 h prior to spawning.


Frameshift and wild-type proteins are often highly similar because the genetic code and genomes were optimized for frameshift tolerance.
Frameshift mutations have been considered of significant importance for the molecular evolution of proteins and their coding genes, while frameshift protein sequences encoded in the alternative reading frames of coding genes have been considered to be meaningless. However, functional frameshifts have been found widely existing. It was puzzling how a frameshift protein kept its structure and functionality while substantial changes occurred in its primary amino-acid sequence. This study shows that the similarities among frameshifts and wild types are higher than random similarities and are determined at different levels. Frameshift substitutions are more conservative than random substitutions in the standard genetic code (SGC). The frameshift substitutions score of SGC ranks in the top 2.0-3.5% of alternative genetic codes, showing that SGC is nearly optimal for frameshift tolerance. In many genes and certain genomes, frameshift-resistant codons and codon pairs appear more frequently than expected, suggesting that frameshift tolerance is achieved through not only the optimality of the genetic code but, more importantly, the further optimization of a specific gene or genome through the usages of codons/codon pairs, which sheds light on the role of frameshift mutations in molecular and genomic evolution.


Vasoactive intestinal polypeptide in the pituitary pars nervosa.
Vasoactive intestinal polypeptide (VIP) is a widely distributed neuropeptide which has recently been found in the hypothalamus and in hypothalamo-hypophyseal portal blood. We have examined the pituitary of several mammalian species for the presence of VIP by immunocytochemistry and radioimmunoassay and report here that the pars nervosa contains a considerable quantity of VIP (100-250 fmol/mg) which, in the dog, can be shown to be present in nerve fibres. It is possible that neurohypophyseal VIP may be a local releasing agent for vasopressin.


Isolated Oculomotor Cranial Nerve Palsy as Unusual Presentation of Primary High-Grade Burkitt's Cell Lymphoma in HIV Patient: Case Report and Literature Review.
Burkitt lymphoma (BL) is a highly aggressive B-cell neoplasm that is well known to be associated with HIV. The presentation usually reflects the underline immunodeficiency state (like opportunistic infections and chronic diarrhea, and enlarged lymph nodes). The most common causes for 3rd cranial nerve palsy are intracranial aneurysm, ischemia, trauma, and migraine. But for our case, it turned out to be associated with underline HIV and BL, which is an unusual cause. Here, we present a 43-year-old gentleman with no past medical history presented to the emergency department with 4 days history of drooping of left eyelid and headache and binocular diplopia with no other neurological features. CT abdomen showed lymph node enlargement. Lymph node biopsy showed the characteristic of Burkitt's cell lymphoma. He was started on chemotherapy, but unfortunately, he died. We're enlightening this case of an isolated oculomotor nerve palsy to diagnose lethal pathology like disseminated BL.


Cord pilot trial: update to randomised trial protocol.
The Cord Pilot Trial aimed to assess the feasibility of conducting a large UK randomised trial to compare the effects of alternative polices for timing of cord clamping (immediate within 20 seconds or deferred after at least 2 minutes) for very preterm birth before 32 weeks gestation. Initial recruitment was from March 2013 to February 2014, phase 2 was from March 2014 to February 2015. This paper updates the pilot trial protocol (Trials 15(1):258, 2014) and presents the changes for phase 2. An electronic randomisation system was introduced at three of the eight pilot sites. For follow-up of children, the Parent Report of Children's Abilities--Revised (PARCA-R) will not be used. For children recruited to the trial during phase 2, follow-up at age 2 years (corrected for gestation at birth) will be by parent completed Ages and Stages Questionnaire (Squire J, Ages and Stages Questionnaires (ASQ), 2009) alone unless funds can be secured for the additional Bayley Scales of Infant Development III (Bayley N, Bayley Scales of Infant and Toddler Development, Third Edition. (Bayley-III), 2005) assessments. To assess accuracy of the cranial ultrasound diagnosis of intraventricular haemorrhage: (i) quality of the scans will be assessed using the British Society of Paediatric Radiology recommendations, and (ii) scan results will be confirmed by independent adjudication. Within and between adjudicator reliability will be assessed. In addition to the analyses planned to assess feasibility of the full trial based on data from the first year of recruitment, data on compliance and outcomes will be presented by allocated group for all women and babies recruited. ISRCTN21456601, registered on 28 February 2013.


Efficacy and safety of Yttrium-90 radioembolization in the treatment of neuroendocrine liver metastases. Long-term monitoring and impact on survival.
Neuroendocrine tumors (NETs) debut in 75% of cases with liver metastases (LMNETs), whose therapeutic approach includes surgical resection and liver transplantation, while liver radioembolization with 90 Y-microspheres (TARE) is reserved for non-operable patients usually due to high tumor burden. We present the accumulated experience of 10 years in TARE treatment of LMNETs in order to describe the safety and the effectiveness of the oncological response in terms of survival, as well as to detect the prognostic factors involved. Of 136 TARE procedures, performed between January 2006 and December 2016, 30 LMNETs (11.1%) were retrospectively analyzed. The study variables were: Tumor response, time to liver progression, survival at 3 and 5 years, overall mortality and mortality associated with TARE. The radiological response assessment was assessed using RECIST 1.1 and mRECIST criteria. An average activity of 2.4 ± 1.3 GBq of 90 Y was administered. No patient presented postembolization syndrome or carcinoid syndrome. There were also no vascular complications associated with the procedure. According to RECIST 1.1 criteria at 6 months, 78.6% presented partial response and 21.4% stable disease, there was no progression or complete response (1 by mRECIST). Survival at 3 and 5 years was 73% in both cases. TARE treatment with 90 Y-microspheres in LMNETs, applied within a multidisciplinary approach, is a safe procedure, with low morbidity, capable of achieving a high rate of radiological response and achieving lasting tumor responses.


Detection of metallo-β-lactamase-encoding genes among clinical isolates of Pseudomonas aeruginosa in northwest of Iran.
The prevalence of metallo-β-lactamase (MBL) production among 104 clinical isolates of Pseudomonas aeruginosa from northwest of Iran was investigated by phenotypic and polymerase chain reaction (PCR) methods. Thirty-nine (37.50%) of isolates were MBL positive by double-disk synergy test. Results of PCR revealed that 18 (17.31%) and 6 (5.77%) imipenem nonsusceptible isolates of P. aeruginosa carried bla(VIM) and bla(IMP) genes respectively, while 92.4% (62/67) of isolates contained class 1 integron gene. This is the first report of MBL-producing P. aeruginosa from northwest of Iran.


Quality of life after prostate cancer treatments in patients comparable at baseline.
Previous studies on the effects of different prostate cancer treatments on quality of life, were confounded because patients were not comparable. This study examined treatment effects in more comparable groups. From 2008-2011, 240 patients with localised prostate cancer were selected to be eligible for both radical prostatectomy (RP) and external beam radiotherapy (EBRT). Brachytherapy (BT) was a third option for some. Health-related quality of life was measured by expanded prostate cancer index composite (EPIC) up to 12 months after treatment. In the sexual domain, RP led to worse summary scores (P<0.001) and more often to a clinically relevant deterioration from baseline than BT and EBRT (79%, 33%, 34%, respectively). In the urinary domain, RP also led to worse summary scores (P=0.014), and more deterioration from baseline (41%, 12%, 19%, respectively). Only on the irritative/obstructive urinary scale, more BT patients (40%) showed a relevant deterioration than RP (17%) and EBRT patients (11%). In the bowel domain, the treatment effects did not differ. This study provides a more unbiased comparison of treatment effects, as men were more comparable at baseline. Our results suggest that, for quality of life, radiotherapy is as least as good an option as RP for treating localised prostate cancer.


Possible role of cytomegalovirus in the pathogenesis of inflammatory aortic diseases: a preliminary report.
To search for possible evidence of a relationship between human cytomegalovirus and aortic diseases, we examined 41 aortic lesions excised at surgery and 16 aortic tissues obtained at autopsy for the presence of cytomegalovirus DNA, by use of polymerase chain reaction. Cytomegalovirus DNA was present in seven (88%) of eight lesions of inflammatory aortic diseases with periaortic fibrosis, five of six inflammatory aneurysms, and all of two aortic occlusive lesions with inflammation. Cytomegalovirus DNA was detected in 20 (61%) of 33 atherosclerotic aneurysms, whereas it was detected in only five (31%) of 16 autopsy samples that showed neither inflammation nor atherosclerosis. Thus the possibility that cytomegalovirus may play a role in the pathogenesis of inflammatory aortic diseases warrants further attention.