Vestibular migraine and persistent postural perceptual dizziness: Handicap, emotional comorbidities, quality of life and personality traits.
To compare vestibular migraine (VM) and persistent postural-perceptual dizziness (PPPD) regarding dizziness associated handicap, emotional and somatic disorders, health-related quality of life (QoL) and personality traits. Thirty patients for each group [VM, PPPD and healthy volunteers (HC)] were studied. Dizziness Handicap Inventory (DHI), Beck depression and anxiety scales, Somatic Symptom Scale-8 (SSS-8), Short Form (36) Health Survey (SF 36) and the Big Five Inventory (BFI) were used. DHI sub-scores were significantly high in both patient groups in comparison with the HC (p < 0.001 for all). Emotional (p = 0.001) and functional (p = 0.022) sub-scores of the PPPD patients were worse. Anxiety and somatic symptom scores of VM (p = 0.026 and p < 0.001 respectively) and PPPD (p < 0.001 for both) and depression scores of the PPPD (p = 0.003) were higher than the HC. Both anxiety (p = 0.009) and somatization (p = 0.005) scores of the PPPD patients were higher than the VM. SF-36subscales were affected in both groups (p < 0.05). Vitality (p = 0.002), mental health (p = 0.045) and social role functioning (p = 0.006) of the PPPD group were worse than the VM. Higher scores for neuroticism (p < 0.001) was present for both groups. Scores for extraversion was low in PPPD patients (p = 0.010) in comparison with the HC. Dizziness associated handicap, anxiety and somatic symptom burden is high in both groups, even higher in PPPD with additional depression. Severe impairment in QoL is present with more severe impairment in emotional aspects in patients with PPPD. Neuroticism is a common personality trait for both groups with additional introversion in PPPD.


Purification of rat pineal hydroxyindole-O-methyltransferase using S-adenosyl-L-homocysteine agarose chromatography.
Rat pineal hydroxyindole-O-methyltransferase (HIOMT; EC 220.127.116.11) was purified by affinity chromatography using an S-adenosyl-L-homocysteine agarose column. This single-step procedure, which is rapid, simple, and applicable to small quantities of tissue, gave a large enrichment of a protein (Mr approximately 38,000) identified by SDS-PAGE and silver staining. The amino acid composition of rat HIOMT was generally similar to that of the bovine enzyme, although some differences were apparent. This method will be valuable in isolating sufficient rat HIOMT to enable its primary amino acid sequence to be determined.


Loss of Claudin-3 Impairs Hepatic Metabolism, Biliary Barrier Function, and Cell Proliferation in the Murine Liver.
Tight junctions in the liver are essential to maintain the blood-biliary barrier, however, the functional contribution of individual tight junction proteins to barrier and metabolic homeostasis remains largely unexplored. Here, we describe the cell type-specific expression of tight junction genes in the murine liver, and explore the regulation and functional importance of the transmembrane protein claudin-3 in liver metabolism, barrier function, and cell proliferation. The cell type-specific expression of hepatic tight junction genes is described using our mouse liver single-cell sequencing data set. Differential gene expression in Cldn3-/- and Cldn3+/+ livers was assessed in young and aged mice by RNA sequencing (RNA-seq), and hepatic tissue was analyzed for lipid content and bile acid composition. A surgical model of partial hepatectomy was used to induce liver cell proliferation. Claudin-3 is a highly expressed tight junction protein found in the liver and is expressed predominantly in hepatocytes and cholangiocytes. The histology of Cldn3-/- livers showed no overt phenotype, and the canalicular tight junctions appeared intact. Nevertheless, by RNA-seq we detected a down-regulation of metabolic pathways in the livers of Cldn3-/- young and aged mice, as well as a decrease in lipid content and a weakened biliary barrier for primary bile acids, such as taurocholic acid, taurochenodeoxycholic acid, and taurine-conjugated muricholic acid. Coinciding with defects in the biliary barrier and lower lipid metabolism, there was a diminished hepatocyte proliferative response in Cldn3-/- mice after partial hepatectomy. Our data show that, in the liver, claudin-3 is necessary to maintain metabolic homeostasis, retention of bile acids, and optimal hepatocyte proliferation during liver regeneration. The RNA-seq data set can be accessed at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE159914.


RNA-DNA hybridization: demonstration in a mammalian system of competition by preincubation.
Nonspecific intermolecular interactions obscure the interpretation of competition experiments involving hybridization of DNA and RNA in mammalian systems when the labeled RNA/DNA ratio is low. The effect of these interactions can be minimized by choosing a sufficiently high ratio of labeled RNA/DNA. No serious effect of nonspecific interactions is observed in bacteriophage systems, even at very low labeled RNA/DNA ratios.


Prism adaptation test before strabismus surgery in patients with decompensated esophoria and decompensated microesotropia.
To evaluate the effect of Prism adaptation test (PAT) on the angle of squint in decompensated esophoria (decEPH) and decompensated microesotropia (decMET). In this single-center retrospective study we reviewed the medical records of patients with the diagnosis of decEPH or decMET, aged at least 12 years, who were treated by strabismus surgery for the first time. The maximum Angle of squint (AOS) for far (F) and near (N) fixation and PAT results before surgery, as well as AOS (F) and AOS (N) after surgery and results of binocular function tests were considered. PAT included wearing a prism based on the largest angle for over 60 min. 100 patients (mean age 37 ± 17 years) were included in the decEPH group, 82 patients (mean age 30 ± 13 years) in the decMET group. For decEPH, before surgery AOS was 25.5 ± 8.8 pdpt (F) and 23.5 ± 9.8 pdpt (N). During PAT the AOS increased significantly by 2.7 ± 4.3 to 28.2 ± 8.6 pdpt (F) and by 4.9 ± 4.5 to 28.3 ± 9.5 pdpt (N). Altogether, in 82% of decEPH patients AOS (F) and/ or AOS (N) in- or decreased by at least 3 pdpt. For decMET, before surgery AOS was 28.6 ± 10.8 pdpt for far (F) and 30.9 ± 11.8 pdpt for near fixation (N). During PAT the AOS increased significantly by 4.2 ± 5.8 to 32.5 ± 9.5 pdpt (F) and by 3.7 ± 6.1 to 34.4 ± 9.5 pdpt (N). Altogether, in 51% of decMET patients, AOS (F) and/ or AOS (N) increased by at least 10 pdpt, therefore more than 5° which would have been maximally expected from mictrotropia, or decreased by at least 3 pdpt. The Prism adaptation test (PAT) showed remarkable changes in AOS in both decEPH and decMET. In patients with decEPH, the preoperative assessment of the "true AOS" under PAT reflects a pivotal requirement for successful strabismus surgery, as 82% had dose relevant angle changes ≥ 3 pdpt. For patients with decMET the preoperative prism adaptation test is especially of diagnostic value, but also 51% of decMET patients had changes in AOS beyond the expected microtropic angle (≥ 10 pdpt) or even a dose relevant angle decrease (≥ 3pdpt).


[Evaluation of competences in scientific writing after two different types of training courses: SCRIU-B study protocol].
Scientific writing is one of the competences required and requested by health professionals. There are several course formats designed for acquiring these competences, although the improvement after taking part in these courses is not always demonstrated. Through an open and non-randomized experimental design, the SCRIU-B study aims to evaluate the acquisition of competencies in scientific writing after specific training courses (face-to-face and online) as well as the satisfaction of the participants with these courses. A control group with participants from other training workshops not related to scientific writing is included. Through different questionnaires about knowledge, attitudes and skills we will evaluate and compare the improvement of their scientific writing skills. The results of the study will allow us to assess the usefulness of these courses and improve their format and implementation.


Comparative transcriptome analysis reveals the regulation network for fiber strength in cotton.
Determine the effect of secondary cell wall (SCW) thickness and microcrystalline cellulose content (MCC) on mature fiber strength (FS) and reveal through comparative transcriptome analysis the molecular regulation network governing FS in cotton. Transmission electron microscope (TEM) analysis of two parent varieties, Prema with elite FS and 86-1 with weak fiber, revealed significant difference in the SCW but not in MCC. Transcriptome analysis revealed that genes differentially expressed during SCW thickening (20 DPA) are highly related to FS; in particular, up-regulated genes such as UDPG, CESA2, and NAC83 were important in SCW thickening, likely contributing to higher FS. GO and KEGG enrichment analysis revealed the common up-regulated genes to be enriched in carbon metabolism and terms relating to the cell wall. We developed two recombinant inbred lines with elite FS, selected from the filial generation of Prema and 86-1. By comparing transcriptomic data, we revealed the gene expression network governing SCW thickness in mature fiber. Our results provide solid insights into the relationship of the SCW and FS.


The Significant Influence of Hoarseness Levels in Connected Speech on the Voice-Related Disability Evaluated Using Voice Handicap Index-10.
This retrospective study examines the influence of voice quality in connected speech (CS) and sustained vowels (SV) on the voice-related disability in patients' daily living documented by Voice Handicap Index-10 (VHI-10). A total of 500 voice recordings of CS and SV samples from 338 patients with voice disturbances were included, along with the patients' age, diagnoses, maximum phonation time, and VHI-10. Dataset-1 comprised of 338 untreated patients, whereas Dataset-2 included 162 patients before and after phonosurgeries. As a preliminary study, the concurrent and diagnostic validities based on auditory-perceptual judgments were examined for cepstral peak prominence (CPP) and CPP smoothed (CPPS) for CS and SV tasks. Next, simple correlations and multivariate regression analyses (MRA) were performed to identify which of the acoustic measures for the CS or SV tasks significantly influenced the total score or improvement of VHI-10. The preliminary study confirmed high correlations with hoarseness levels as well as the excellent diagnostic accuracy of CPP and CPPS for both CS and SV tasks. In Dataset-1, the simple correlations and MRA results showed that cepstral measures in both tasks demonstrated moderate correlations with, and significant contribution to the total score of VHI-10, respectively. However, in Dataset-2, the changes of cepstral measures, as well as the median pitch after phonosurgeries in the CS tasks only, showed significant contributions to the improvement of VHI-10. The study demonstrated that the hoarseness levels in both the CS and SV tasks equivalently influenced the VHI-10 scores, and that the post-surgical change of voice quality only in the CS tasks influenced the improvement of voice-related disability in daily living.


Comparison of hematologic consequences and efficacy of p-aminophenones in mice.
Controlled methemoglobin (MHb) formation is one strategy employed to counter cyanide (CN) toxicity. Currently available MHb formers present certain drawbacks and limitations. The purpose of this study was to characterize, in mice, the hematologic effects of the MHb-forming compound p-aminopropiophenone (PAPP), and two structurally-related p-aminophenones, p-aminoheptanoylphenone (PAHP) and p-aminooctanoylphenone (PAOP). Although these three p-aminophenones have been shown previously to be efficacious as pretreatments against CN, a more complete understanding of their hematologic effects is lacking. In addition, because the active form of PAPP has been shown to be its N-hydroxy metabolite, the N-hydroxy metabolites of PAPP, PAHP and PAOP were also tested. Using a hemoximeter, blood samples obtained -2 to +180 min relative to intramuscular (i.m.) or intraperitoneal (i.p.) drug injections were evaluated. Sodium nitrite (NaNO(2)) and the appropriate solvents served as the positive and negative controls, respectively. Dose-, time-, route-, and compound-related effects were observed. MHb and sulfhemoglobin levels increased, whereas levels of those parameters related to oxygen-carrying capacity of the blood, such as, oxygen saturation and oxyhemoglobin decreased. In general, the effects of PAHP and PAOP were longer lasting than those of PAPP and NaNO(2). Furthermore, PAPP and NaNO(2) were equally effective with either route of administration. Conversely, PAHP and PAOP showed larger effects when administered i.p. versus i.m. The animals treated with N-hydroxy metabolites of the p-aminophenones also showed similar changes in the hematological parameters measured. N-hydroxy PAPP was shown to be the most rapidly acting MHb-forming compound examined in this series. It could achieve therapeutic concentrations of MHb within 2 min and thus may be considered as a treatment for CN intoxication. Although additional work is needed, these data provide information that will be useful for the successful development of improved anti-CN MHb formers.


Sperm head morphometry and chromatin condensation are in constant change at seminiferous tubules, epididymis, and ductus deferens in bulls.
The aim of this study was to evaluate the sperm head morphometry and chromatin condensation at different regions of the reproductive tract in bulls. Sperm smears of seminiferous tubules (ST), epididymis head (EH), body (EB), and tail (ET), and ductus deferens (DD) were stained with toluidine blue. Afterwards, the sperm head morphometry and chromatin alteration types were evaluated by a computational image analysis. Overall, spermatozoa of ST had lower (P < 0.05) area (A), perimeter (P), width (W), length (L), ellipticity (E), and Fourier harmonics (F0, F1, and F2). The chromatin decondensation (CD) and heterogeneity (CH) were higher (P < 0.05) in the ST region and decreased (P < 0.0001) during the migration along the reproductive tract (ST - DD direction). Considering the factors extracted (Factors 1 and 2) by the principal component analysis, the parameters A, P, W, L, and F0 were responsible for ∼36% of the Factor 1, while the E, F0, F1, and anterior-posterior symmetry (APS) contributed ∼27% to Factor 2. Both, CD and CH were associated with Factor 1 in the EH and ET regions and Factor 2 in the ST. Also, a well-defined difference between sperm heads collected from the ST and DD regions was observed by canonical analysis. The distribution of each chromatin alteration type was recorded. The proportion of normal sperm was lower (P < 0.05) in ST compared to other regions. Moreover, the chromatin influenced the morphometry and sperm heads with whole chromatin alteration type showed a smaller (P < 0.05) A, P, W, L, and E. In summary, the epididymal maturation is important for chromatin compaction and final morphometry of the sperm head. Also, the identification and quantification of the sperm chromatin condensation in different regions of reproductive tract can be used as potential biomarkers to predict the fertility in bulls.


Novel insights into mixotrophic cultivation of Nitzschia laevis for co-production of fucoxanthin and eicosapentaenoic acid.
The aim of this study was to determine a compatible method for co-production of fucoxanthin and eicosapentaenoic acid of diatom Nitzschia laevis by mixotrophic and heterotrophic cultivation modes in view of cell growth, targeting products' contents, photosynthesis-related characteristics and carbon partitioning. The results showed that mixotrophic mode enhanced fucoxanthin and eicosapentaenoic acid yields by increasing their precursors of pyruvate and acetyl-CoA at the expense of starch. The increase of chlorophylls and glyceraldehyde 3-phosphate indicated the development of Calvin cycle and carbon repartitioning in mixotrophic mode. Consequently, microalgal cells in mixotrophic mode achieved much higher fucoxanthin (60.12%) and eicosapentaenoic acid (50.67%) contents, and lower starch content (30.2%) compared with heterotrophic mode. Furthermore, fucoxanthin content was positively correlated with eicosapentaenoic acid content (adjusted R2 = 0.96). Taken together, these results showed that the mixotrophic mode could be a promising approach for the co-production of fucoxanthin and eicosapentaenoic acid by Nitzschia laevis.


Urgent endarterectomy for symptomatic carotid occlusion is associated with a high mortality.
Interventions for carotid occlusions undertaken are undertaken and the outcomes are poorly defined. We sought to study patients undergoing urgent carotid revascularization for symptomatic occlusions. The Society for Vascular Surgery Vascular Quality Initiative database was queried from 2003 to 2020 to identify patients with carotid occlusions undergoing carotid endarterectomy. Only symptomatic patients undergoing urgent interventions within 24 hours of presentation were included. Patients were identified based on computed tomography and magnetic resonance imaging. This cohort was compared with symptomatic patients undergoing urgent intervention for severe stenosis (≥80%). The primary end points were perioperative stroke, death, myocardial infarction (MI) and composite outcomes as defined by the Society for Vascular Surgery reporting guidelines. Patient characteristics were analyzed to determine predictors of perioperative mortality and neurological events. We identified 390 patients who underwent urgent CEA for symptomatic occlusions. The mean age was 67.4 ± 10.2 years (range, 39-90 years). The cohort was predominantly male (60%) with associated risk factors for cerebrovascular disease, including hypertension (87.4%), diabetes (34.4%), coronary artery disease (21.6%), and current smoking (38.7%). This population had high use of medications, including statins (78.6%), P2Y12 inhibitors (32.0%), aspirin (77.9%), and renin-angiotensin inhibitors (43.7%) preoperatively. When compared with patients undergoing urgent endarterectomy for severe stenosis (≥80%), those with symptomatic occlusion were well-matched with regard to risk factors, but the severe stenosis cohort seemed to be managed better medically and less likely to present with cortical stroke symptoms. Perioperative outcomes were significantly worse for the carotid occlusion cohort, primarily driven by higher perioperative mortality (2.8% vs 0.9%; P < .001). The composite end point of stroke/death/MI was also significantly worse in the occlusion cohort (7.7% vs 4.9%; P = .014). On multivariate analysis, carotid occlusion was associated with increased mortality (odds ratio, 3.028; 95% confidence interval, 1.362-6.730; P = .007) and composite outcome of stroke, death, or MI (odds ratio, 1.790; 95% confidence interval, 1.135-2.822; P = .012). Revascularization for symptomatic carotid occlusion constitutes approximately 2% of carotid interventions captured in the Vascular Quality Initiative, affirming the rarity of this undertaking. These patients have acceptable rates of perioperative neurological events, but are at an elevated risk of overall perioperative adverse events, primarily driven by higher mortality, compared with those with severe stenosis. Carotid occlusion seems to be the most significant risk factor for the composite end point of perioperative stroke, death, or MI. Although intervention for a symptomatic carotid occlusion may be performed with acceptable rate of perioperative complications, judicious patient selection is warranted in this high-risk cohort.


USRC: a new strategy for adding digital images to the medical school curriculum.
Many medical schools use learning management systems (LMSs) to give students access to online lecture notes, assignments, quizzes, and other learning resources. LMSs can also be used to provide access to digital radiology images, potentially improving preclinical teaching in anatomy, physiology, and pathology while also allowing students to develop interpretation skills that are important in clinical practice. However, it is unclear how radiology images can best be stored, imported, and displayed in an LMS. We developed University of Saskatchewan Radiology Courseware (USRC), a new web application that allows course designers to import images into pages linked to BlackBoard Learn, a popular LMS. Page content, including images, annotations, captions, and supporting text, are stored as teaching cases on a MIRC (Medical Imaging Resource Center) server. Course designers create cases in MIRC, and then create a corresponding page in BlackBoard by modifying an HTML template so that it holds the URL of a MIRC case. When a user visits the page in BlackBoard, the page requests content from the MIRC case, reformats the text for display in BlackBoard, and loads an image viewer plug-in that allows students to view and interact with the images stored in the case. The USRC technology can be used to reformat MIRC cases for presentation in any website or in any learning management system that supports custom pages written in HTML with embedded JavaScript.


Severe hand, foot and mouth disease associated with Coxsackievirus A10 infections in Xiamen, China in 2015.
Coxsackievirus A10 (CV-A10) is one of the etiological agents associated with hand, foot and mouth disease (HFMD) and usually causes mild cases. During 2009-2014, no severe cases caused by CV-A10 was reported in Xiamen, China, however, an increase in cases was seen in 2015. We aimed to perform a retrospective molecular epidemiological analysis of HFMD associated with CV-A10 infections in Xiamen. CV-A10 VP1 (n=41) capsid and full-length or near full-length genomes (n=14) were sequenced. Phylogenetic trees were constructed based on these sequences and other reference sequences and nucleotide and amino acid changes were characterized. From 2009-2014, no laboratory-confirmed CV-A10 infections associated with severe cases were identified, however, in 2015, 39% (7/18) of severe HFMD cases were CV-A10 infections. Sequence analysis of severe and non-severe CV-A10 HFMD cases determined that severe cases predominantly clustered with an emerging clade E lineage A strain which contained 4 nucleotide changes in 5' UTR and 5 amino acid substitutions in structural and non-structural proteins. The results indicate CV-A10 infection may be emerging as a new and major cause of severe HFMD and CV-A10 surveillance should be increased and considered in HFMD prevention and control strategies.


Effects of cardiac medications on ventricular function in patients with Duchenne muscular dystrophy-related cardiomyopathy.
The DMD Care Considerations Working Group Guidelines 2010 recommended treating cardiac dystrophinopathy with angiotensin-converting enzyme-inhibitor (ACEi) and beta-blocker (BB) therapy to prevent the progressive decline in left ventricular function expected from earlier, natural history studies. The aim of this research was to audit change in measures of left ventricular function over 8 years to 4 years before and 4 years after deploying an ACEi/BB combination systematically at a dedicated "cardiology-muscle" clinic. This is an institutionally registered, retrospective, case-file-based audit of serial echocardiographic measures of left ventricular fractional shortening accumulated over the period 1995 to 2015. Data from 104 genetically confirmed Duchenne muscular dystrophy (DMD) patients, aged 22.2 ± 5.3 years at data censure, were included. Mean age at first detection of left ventricular dysfunction was 15.1 ± 4.2 years, but older in those on maintenance steroid therapy (16.8 ± 4.2 vs 14.5 ± 4.1 years; P = .04). Group mean fractional shortening fell by 1.5%/year over the 4 years before therapy, but this decreased to 0.9%/year over the first 4 years after starting therapy. Analysis of limited left ventricular ejection fraction measures showed similar but nonsignificant changes. Neither age at detection of left ventricular dysfunction nor fractional shortening percent at time of therapy initiation affected the beneficial response. The results support the international DMD recommendations of the time. This combination of cardiac medications helps stabilize heart function. For the best long-term effects, therapy needs to be initiated no later than on first detection left ventricular impairment.


Intraoperative corneal pachymetry in eyes having radial keratotomy.
We prospectively studied 45 eyes that had radial keratotomy for correction of myopia to determine whether significant changes in corneal thickness occurred during the surgical procedure and which paracentral corneal region was the thinnest consistently. We used a standard bidirectional technique with a diamond knife. The inferotemporal paracentral region was the thinnest most frequently (38% of eyes) both pre-incision and post-incision. However, each of the other paracentral regions measured the thinnest in a smaller percentage of eyes: temporal (28% pre-incision and post-incision); inferior (19% pre-incision, 21% post-incision); nasal (11% pre-incision, 9% post-incision); superior (4% pre-incision and post-incision). A statistically significant reduction in corneal thickness occurred intraoperatively in all regions.


Serum amyloid protein (SAA) as a healthy marker for immune function in Tridacna crocea.
Serum amyloid protein (SAA) is known as an acute reactive protein of innate immunity in mammals. However, in invertebrates, the role of SAA in innate immunity is still unclear. In this study, a full-length cDNA of the SAA gene (named TcSAA) was cloned from Tridacna crocea, mollusca. The gene includes a 193 bp 5' untranslated region (UTR) and a 129 bp 3' UTR sequence, and the open reading frame (ORF) with 393 bp nucleotides encodes a polypeptide of 130 amino acids. TcSAA contains a typical signal peptide and an SAA functional domain. The mRNA expression of TcSAA was detected in all 12 selected tissues and 7 different developmental stages. Furthermore, the expression of TcSAA was increased quickly in hemocytes after challenge with V. coralliilyticus or LPS. Furthermore, rTcSAA could bind V. coralliilyticus and V. alginolyticus, and the protein could reduce the lethality rate of the clams from 80% to 55% which caused by V. coralliilyticus about 48 h after injection. In summary, these results indicate that TcSAA may act as a marker for monitoring health and protecting T. crocea.


Characterization of the Mas-related gene family: structural and functional conservation of human and rhesus MrgX receptors.
Recently, a large family of G-protein-coupled receptors called Mas-related genes (Mrgs), which is selectively expressed in small-diameter sensory neurons of dorsal root ganglia, was described. A subgroup of human Mrg receptors (MrgX1-X4) is not found in rodents and this has hampered efforts to define the physiological roles of these receptors. MrgX receptors were cloned from rhesus monkey and functionally characterized alongside their human orthologs. Most of the human and rhesus MrgX receptors displayed high constitutive activity in a cellular proliferation assay. Proliferative responses mediated by human or rhesus MrgX1, or rhesus MrgX2 were partially blocked by pertussis toxin (PTX). Proliferative responses mediated by rhesus MrgX3 and both human and rhesus MrgX4 were PTX insensitive. These results indicate that human and rhesus MrgX1 and MrgX2 receptors activate both Gq- and Gi-regulated pathways, while MrgX3 and MrgX4 receptors primarily stimulate Gq-regulated pathways. Peptides known to activate human MrgX1 and MrgX2 receptors activated the corresponding rhesus receptors in cellular proliferation assays, Ca(2+)-mobilization assays, and GTP-gammaS-binding assays. Cortistatin-14 was selective for human and rhesus MrgX2 receptors over human and rhesus MrgX1 receptors. BAM22 and related peptides strongly activated human MrgX1 receptors, but weakly activated rhesus MrgX1, human MrgX2, and rhesus MrgX2 receptors. These data suggest that the rhesus monkey may be a suitable animal model for exploring the physiological roles of the MrgX receptors.


Correction: Enhanced photoluminescence of silicon quantum dots in the presence of both energy transfer enhancement and emission enhancement mechanisms assisted by the double plasmon modes of gold nanorods.
[This corrects the article DOI: 10.1039/D1NA00287B.].


Significance of pacemaker recovery time after the Mustard operation for transposition of the great arteries.
Pacemaker recovery time corrected for cycle length was measured in 24 patients 6 months to 3 years after the Mustard operation for transposition of the great arteries. This index of sinoatrial (S-A) nodal function was obtained by subtracting the control R-R interval from the first R-R interval recorded after 3 minutes of rapid atrial pacing at the superior vena caval-right atrial junction. Recovery times were compared with those of a control group of 54 children with various forms of congenital heart disease who had not had cardiac surgery and whose electrocardiogram revealed normal sinus rhythm. The longest corrected pacemaker recovery time in the control group was 250 msec. Recovery time was normal (mean 115 msec) in 13 of the 24 patients who had undergone the Mustard procedure and prolonged (mean 472 msec) in the other 11. In 4 of these 11 a junctional escape complex was recorded before recovery of the S-A node. The configuration of the P wave and the development of dysrhythmias in the postoperative follow-up period were compared in patients with a normal and a prolonged corrected pacemaker recovery time. The incidence of dysrhythmias was much smaller in the former group. Normal sinus rhythm after the first postoperative week was noted in 10 (76 percent) of patients with a normal corrected pacemaker recovery time but in only 2 (18 percent) of those with an abnormal recovery time. One patient with an abnormal recovery time died suddenly 26 months after operation in spite of good hemodynamic repair. A prolonged pacemaker recovery time after the Mustard operation for transposition of the great arteries indicated that rhythm abnormalities were likely to develop, but a normal recovery time did not exclude abnormal sinus nodal function.


Expression and chromosomal assignment of PTPH1 gene encoding a cytosolic protein tyrosine phosphatase homologous to cytoskeletal-associated proteins.
We have investigated the mRNA expression of 2 human protein tyrosine phosphatases with sequence homology to cytoskeletal proteins, PTPH1 and PTPMEG. Northern-blot analysis of PTPH1 using poly (A)+ RNA from normal human colon tissue showed a low-abundance message of 4.3 kb. Reverse-transcriptase/polymerase-chain reaction (RT-PCR) was therefore used to detect it in a wide variety of cell lines including 9 colorectal, 5 gastric, 5 hepatic and 6 hematopoietic tumor cells. PTPH1 mRNA was not detected only in Colo 320 cells over-expressing c-myc mRNA, among the colorectal cancer cell lines examined. When Colo 320 cells were incubated with 5 mM sodium butyrate for 5 days, PTPH1 mRNA became detectable, concomitant with the marked decrease in the expression level of c-myc mRNA. Moreover, the chromosomal localization of PTPH1 gene was investigated by fluorescence in situ hybridization. Interestingly, PTPH1 gene was mapped to 9q31 where the gene for Gorlin syndrome, a putative tumor suppressor gene, exists.


The blood tumour barrier in intracranial tumours studied with X-ray computed tomography and positron emission tomography using 68-Ga-EDTA.
Disruption of the blood brain barrier or rather blood tumour barrier in cerebral tumours was studied with CT after intravenous injection of contrast medium and with PET after intravenous administration of 68-Ga-EDTA. Histology from stereotactic biopsies or open surgery is compared with the radiologic findings and advantages of the respective methods are discussed. The material consisted of 47 patients mainly with supratentorial gliomas and a few miscellaneous tumours. Astrocytomas (Kernohan grade II) were found to have no disruption of blood tumour barrier while anaplastic astrocytomas and glioblastomas (Kernohan grade III and IV) had. PET is somewhat superior to CT in detection of disruption of the blood tumour barrier. It is concluded that the combination of CT and PET is of value in the assessment of intracranial tumours.


Physical activity and urologic cancers.
Despite convincing evidence that physical activity protects against colon and breast cancers, the association of physical activity with urologic cancers is less well explored. Expert panels have previously found a probably protective benefit for prostate cancer, but insufficient evidence for other urologic cancers. We review the evidence for testicular, kidney/renal, bladder, and prostate cancers, including whether benefits may exist within subgroups. While the limited evidence base does not support an association of physical activity with either testicular or bladder cancers, a growing body of research suggests that physical activity results in a modest risk reduction for kidney cancer. A large number (>30) of studies suggests a probable small decrease in prostate cancer risk among those who are physically active, which is likely driven by the effect on advanced/aggressive tumors. The role of physical activity in decreasing urologic cancer risk is thus likely limited to advanced prostate and possibly kidney cancers with no association in testicular or bladder cancers.


Heavy menstrual bleeding in women on anticoagulant treatment for venous thromboembolism: Comparison of high- and low-dose rivaroxaban with aspirin.
Rivaroxaban may induce heavy menstrual bleeding. It is unknown if this effect is dose related or if rivaroxaban is associated with more menstrual bleeding than aspirin. To demonstrate and compare menstrual patterns and actions taken among women receiving aspirin and two doses of rivaroxaban. The EINSTEIN-CHOICE trial compared once-daily rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin 100 mg for extended treatment of venous thromboembolism in patients who had completed 6 to 12 months of anticoagulant therapy. In 362 women with menstrual cycles, menstrual flow duration and intensity assessed at days 30, 90, 180, and 360 were compared with those before starting anticoagulant therapy. Menstrual flow duration increased in 12%-18% of the 134 women given 20-mg rivaroxaban, in 6% to 12% of 120 women given 10-mg rivaroxaban, and in 9% to 12% of 108 women given aspirin. Corresponding increases in flow intensity were 19% to 24%, 14% to 21%, and 13% to 20%. The odds ratios (ORs) for increased menstrual flow duration were 1.36 (95% confidence interval [CI], 0.62-2.96) for rivaroxaban 20 mg versus aspirin, 0.77 (95% CI, 0.33-1.81) for rivaroxaban 10 mg versus aspirin, and 0.57 (95% CI, 0.26-1.25) for rivaroxaban 10 mg versus 20 mg. The ORs for increased menstrual flow intensity were 1.41 (95% CI, 0.67-2.99), 1.07 (95% CI, 0.49-2.34), and 0.76 (95% CI, 0.37- 1.57), respectively. There were no statistically significant differences in menstrual hemorrhage patterns between women treated with 10 or 20 mg of rivaroxaban and aspirin. Compared with 10-mg rivaroxaban or aspirin, 20-mg rivaroxaban showed numerically more often increased menstrual flow duration and intensity.


Reduced recovery of dieldrin residues-a shortcoming of sulfuric cleanup of biological samples.
Reduced quantitative recovery of dieldrin (1, 2, 3, 4, 10, -10-hexachloro-6, 7-epoxy-1, 4, 4a, 5, 6, 7, 8, 8a-octahydro-1, 4-endo, exo-5, 8-dimethanoaphthalene) while using concentrated sulfuric acid for the cleanup of the extracted samples, has been investigated by gas-liquid chromatography and infrared (IR) spectroscopy. In vitro studies have shown that the servere breakdown in the recovery of dieldrin can be checked if 65% (v/v) H2SO4 is used as opposed to the concentrations greater than 70% sulfuric acid, the epoxide ring attached to the norbornene nucleus of dieldrin undergoes rearrangement to form keto-dihydroaldrin.


Improving Photoelectrochemical Activity of Magnetron-Sputtered Double-Layer Tungsten Trioxide Photoanodes by Irradiation with Intense Pulsed Ion Beams.
The photoelectrochemical (PEC) activity of metal oxide photoelectrodes for water-splitting applications can be boosted in several different ways. In this study, we showed that PEC activity can be significantly improved with a double-layer (crystalline-amorphous) configuration of WO3 thin films irradiated with intense pulsed ion beams (IPIB) of a nanosecond duration. It was found that IPIB irradiation promotes the formation of crystalline and sponge-like WO3 structures on the surface. Due to an increase in the active surface and light scattering in irradiated samples, photocurrent generation increased by ~80% at 1.23 reversible hydrogen electrodes (RHE).


Plasma inflammatory cytokines and survival of pancreatic cancer patients.
Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome. We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for death were estimated using multivariate Cox proportional hazards models. Overall mortality was significantly increased in patients in the top quartile of CRP (HR = 2.52, 95% CI: 1.82-3.49), IL-6 (HR = 2.78, 95% CI: 2.03-3.81), sTNF-RII (HR = 2.00, 95% CI: 1.46-2.72), and MIC-1 (HR = 2.53, 95% CI: 1.83-3.50), compared to those in the bottom quartile (P-trend <0.0001 for all four comparisons). Furthermore, patients with higher circulating concentrations of all four cytokines had a median survival of 3.7 months; whereas, those with lower levels had a median survival of 19.2 months (HR = 4.55, 95% CI: 2.87-7.20, P-trend <0.0001). Individual elevated plasma inflammatory cytokines are associated with significant and dramatic reductions in pancreatic cancer patient survival. Furthermore, we observed an independent combined effect of those cytokines on patient survival, suggesting that multiple inflammatory pathways are likely involved in PDAC progression. Future research efforts to target the inflammatory state using combination strategies in pancreatic cancer patients are warranted.


Modeling host-microbiome interactions for the prediction of meat quality and carcass composition traits in swine.
The objectives of this study were to evaluate genomic and microbial predictions of phenotypes for meat quality and carcass traits in swine, and to evaluate the contribution of host-microbiome interactions to the prediction. Data were collected from Duroc-sired three-way crossbred individuals (n = 1123) that were genotyped with a 60 k SNP chip. Phenotypic information and fecal 16S rRNA microbial sequences at three stages of growth (Wean, Mid-test, and Off-test) were available for all these individuals. We used fourfold cross-validation with animals grouped based on sire relatedness. Five models with three sets of predictors (full, informatively reduced, and randomly reduced) were evaluated. 'Full' included information from all genetic markers and all operational taxonomic units (OTU), while 'informatively reduced' and 'randomly reduced' represented a reduced number of markers and OTU based on significance preselection and random sampling, respectively. The baseline model included the fixed effects of dam line, sex and contemporary group and the random effect of pen. The other four models were constructed by including only genomic information, only microbiome information, both genomic and microbiome information, and microbiome and genomic information and their interaction. Inclusion of microbiome information increased predictive ability of phenotype for most traits, in particular when microbiome information collected at a later growth stage was used. Inclusion of microbiome information resulted in higher accuracies and lower mean squared errors for fat-related traits (fat depth, belly weight, intramuscular fat and subjective marbling), objective color measures (Minolta a*, Minolta b* and Minolta L*) and carcass daily gain. Informative selection of markers increased predictive ability but decreasing the number of informatively reduced OTU did not improve model performance. The proportion of variation explained by the host-genome-by-microbiome interaction was highest for fat depth (~ 20% at Mid-test and Off-test) and shearing force (~ 20% consistently at Wean, Mid-test and Off-test), although the inclusion of the interaction term did not increase the accuracy of predictions significantly. This study provides novel insight on the use of microbiome information for the phenotypic prediction of meat quality and carcass traits in swine. Inclusion of microbiome information in the model improved predictive ability of phenotypes for fat deposition and color traits whereas including a genome-by-microbiome term did not improve prediction accuracy significantly.


Utility of pre-transplant lower urinary tract investigation in pediatric renal transplant population after referral: A 16-year institutional experience.
To evaluate the clinical utility of pre-renal transplant LUT investigations in pediatric populations after their referral for transplant evaluation based on the etiology of their ESRD. A 16 year retrospective review of patients undergoing RT performed at our institution was performed. Patients were stratified into two groups: Group 1-non-urologic and Group 2-urologic etiology for ESRD. Baseline characteristics, pre-transplant LUT investigations, and urologic interventions were assessed. One-year clinical outcomes were compared between those with and without LUT investigations following referral for renal transplantation (RT). 227 patients and 97 patients were identified for Groups 1 and 2, respectively. 19% of Group 1 and 73% of Group 2 had VCUG, while 1% and 13%, respectively, had UDS ordered following referral for RT. In both groups, >50% of VCUG and UDS were ordered without specific clinical concerns. These had low likelihood of prompting interventions, both pre-transplant (Group 1-VCUG 0%, UDS 0%; Group 2-VCUG 0%, UDS 8%) or post-transplant (Group 1-0%, Group 2-5%). In both groups, LUT investigation following referral for RT did not lead to differences in 1 year outcomes assessed. In anticipation of pediatric RT, LUT investigations ordered without clinical indications did not provide information that altered management prior to transplantation.


Comments on 'Calculation of water equivalent thickness of materials of arbitrary density, elemental composition and thickness in proton beam irradiation'.
We comment on a previous article by Zhang and Newhauser (2009 Phys. Med. Biol. 54 1383-95) which presents several approximate ways of computing the water equivalent of an arbitrary degrader. First, we present a simple exact method which depends only on the range-energy relation of water and of the degrader material. Second, we point out that any theoretical method, approximate or exact, ultimately depends on the range-energy relation, that is to say, the correct value of the mean excitation energy I for the materials in question. Unfortunately I is particularly problematic for water. Therefore, at the present state of knowledge, we should measure water equivalent, rather than computing it, whenever an accurate value is needed.


Increases in attentional demands are associated with language group differences in working memory performance.
One approach to resolving the controversy over whether bilingualism affects executive function (EF) performance has been to identify the specific tasks and populations that might show these effects. The assumption is that the effect of bilingualism reliably occurs with some tasks and populations but not others and that identifying those conditions will settle outstanding contradictions. However, it is now clear that experiments using the same task (e.g., flanker, Simon, etc.) and apparently the same populations (monolingual or bilingual participants) still lead to different outcomes. Therefore, something in addition to these factors must determine performance. The present study tested the hypothesis that changes in demands for attentional control within a task is associated with performance differences for groups with different attentional resources, in this case, monolingual and bilingual participants. Sixty-four young adults who were classified as monolingual or bilingual based on a detailed questionnaire completed four increasingly difficult conditions of an n-back task while EEG was recorded. Behavioral results showed greater declines with increasing difficulty for monolinguals than bilinguals, and electrophysiological results revealed more effortful processing by monolinguals across all conditions. Our interpretation is that demands for attentional control by the task in conjunction with assessments of attentional resources in individuals or groups determines performance on executive function tasks. These results lead to a re-examination of how executive function is conceptualized and the role of bilingualism in performance on these tasks.


Routine ultrasound examination at 12 or 18 gestational weeks for prenatal detection of major congenital heart malformations? A randomised controlled trial comprising 36,299 fetuses.
To compare the rate of prenatal diagnosis of heart malformations between two policies of screening for heart malformations. Randomised controlled trial. Six university hospitals, two district general hospitals. A total of 39 572 unselected pregnancies randomised to either policy. The 12-week policy implied one routine scan at 12 weeks including measurement of nuchal translucency (NT), and the 18-week policy implied one routine scan at 18 weeks. Fetal anatomy was scrutinised using the same check-list in both groups, and in both groups, indications for fetal echocardiography were ultrasound findings of any fetal anomaly, including abnormal four-chamber view, or other risk factors for heart malformation. In the 12-week scan group, NT >or=3.5 mm was also an indication for fetal echocardiography. Prenatal diagnosis of major congenital heart malformation. In the 12-week scan group, 7 (11%) of 61 major heart malformations were prenatally diagnosed versus 9 (15%) of 60 in the 18-week scan group (P= 0.60). In four (6.6%) women in the 12-week scan group, the routine scan was the starting point for investigations resulting in a prenatal diagnosis versus in 9 (15%) women in the 18-week scan group (P=0.15). The diagnosis was made <or=22 weeks in 5% (3/61) of the cases in the 12-week scan group versus in 15% (9/60) in the 18-week scan group (P=0.08). The prenatal detection rate of major heart malformations was low with both policies. The 18-week scan policy seemed to be superior to the 12-week scan policy, although the differences in prenatal detection rates were not statistically significant.


Dietary Protein and Amino Acid Deficiency Inhibit Pancreatic Digestive Enzyme mRNA Translation by Multiple Mechanisms.
Chronic amino acid (AA) deficiency, as in kwashiorkor, reduces the size of the pancreas through an effect on mammalian target of rapamycin complex 1 (mTORC1). Because of the physiological importance of AAs and their role as a substrate, a stimulant of mTORC1, and protein synthesis, we studied the effect of acute protein and AA deficiency on the response to feeding. ICR/CD-1 mice were fasted overnight and refed for 2 hours with 4 different isocaloric diets: control (20% Prot); Protein-free (0% Prot); control (AA-based diet), and a leucine-free (No Leu). Protein synthesis, polysomal profiling, and the activation of several protein translation factors were analyzed in pancreas samples. All diets stimulated the Protein Kinase-B (Akt)/mTORC1 pathway, increasing the phosphorylation of the kinase Akt, the ribosomal protein S6 (S6) and the formation of the eukaryotic initiation factor 4F (eIF4F) complex. Total protein synthesis and polysome formation were inhibited in the 0% Prot and No Leu groups to a similar extent, compared with the 20% Prot group. The 0% Prot diet partially reduced the Akt/mTORC1 pathway and the activity of the guanine nucleotide exchange factor eIF2B, without affecting eIF2α phosphorylation. The No Leu diet increased the phosphorylation of eIF2α and general control nonderepressible 2, and also inhibited eIF2B activity, without affecting mTORC1. Essential and nonessential AA levels in plasma and pancreas indicated a complex regulation of their cellular transport mechanisms and their specific effect on the synthesis of digestive enzymes. These studies show that dietary AAs are important regulators of postprandial digestive enzyme synthesis, and their deficiency could induce pancreatic insufficiency and malnutrition.


Structures and kinetics of Thermotoga maritima MetY reveal new insights into the predominant sulfurylation enzyme of bacterial methionine biosynthesis.
Bacterial methionine biosynthesis can take place by either the trans-sulfurylation route or direct sulfurylation. The enzymes responsible for trans-sulfurylation have been characterized extensively because they occur in model organisms such as Escherichia coli. However, direct sulfurylation is actually the predominant route for methionine biosynthesis across the phylogenetic tree. In this pathway, most bacteria use an O-acetylhomoserine aminocarboxypropyltransferase (MetY) to catalyze the formation of homocysteine from O-acetylhomoserine and bisulfide. Despite the widespread distribution of MetY, this pyridoxal 5'-phosphate-dependent enzyme remains comparatively understudied. To address this knowledge gap, we have characterized the MetY from Thermotoga maritima (TmMetY). At its optimal temperature of 70 °C, TmMetY has a turnover number (apparent kcat = 900 s-1) that is 10- to 700-fold higher than the three other MetY enzymes for which data are available. We also present crystal structures of TmMetY in the internal aldimine form and, fortuitously, with a β,γ-unsaturated ketimine reaction intermediate. This intermediate is identical to that found in the catalytic cycle of cystathionine γ-synthase (MetB), which is a homologous enzyme from the trans-sulfurylation pathway. By comparing the TmMetY and MetB structures, we have identified Arg270 as a critical determinant of specificity. It helps to wall off the active site of TmMetY, disfavoring the binding of the first MetB substrate, O-succinylhomoserine. It also ensures a strict specificity for bisulfide as the second substrate of MetY by occluding the larger MetB substrate, cysteine. Overall, this work illuminates the subtle structural mechanisms by which homologous pyridoxal 5'-phosphate-dependent enzymes can effect different catalytic, and therefore metabolic, outcomes.


Arachnoiditis ossificans with arachnoid cyst after cranial tuberculous meningitis.
A 34-year-old woman developed symptomatic arachnoiditis ossificans and an arachnoid cyst as a consequence of tuberculous meningitis adequately treated 20 years before. Surgical decompression of the cyst stopped the progression of her spastic paraparesis. Pathologic examination confirmed the presence of ossification of the arachnoid.


Refractive outcome following radial keratotomy and combined radial and astigmatic keratotomy.
To determine whether the visual and refractive outcomes of combined astigmatic and radial keratotomy (AK/RK) procedures was different from that following RK for the correction of naturally occurring compound myopic astigmatism and spherical myopia. Private professional practice, San Diego, California, USA. The computer database of all incisional procedures performed by one surgeon over 10 years was reviewed to compare the visual acuity outcome of AK/RK and RK procedures. Enhancement procedures were excluded. Only data from the last office visits were analyzed to establish the relationship between visual acuity and type of keratotomy procedure performed. A multiple regression model was constructed, which included covariates of age, postoperative keratometric cylinder, and postoperative refraction. After controlling for covariates, the AK/RK population had significantly lower postoperative uncorrected visual acuity levels than the RK population (P < .03) after one operation (prior to enhancement surgery). Using the nomograms for myopia correction for unenhanced RK cases, combined AK and RK procedures appeared to reduce the expected visual results. Surgeons may consider modifying surgical nomograms to account for the expected spherical undercorrection that can occur when myopia and astigmatism are corrected simultaneously.


Management of Neuroendocrine Tumor Liver Metastases: Long-Term Outcomes and Prognostic Factors from a Large Prospective Database.
Liver-directed therapies have been used to treat neuroendocrine liver metastases (NELM) for both symptomatic improvement and tumor growth control. We reviewed our experience with NELM to investigate the outcomes of available treatment modalities and to identify prognostic factors for survival. We identified all patients with NELM, who were managed at our institution, from a prospectively collected institutional database. Overall survival (OS) was determined for each treatment modality. Between 2003 and 2010, we identified 939 patients with neuroendocrine tumors, of whom 649 patients had NELM. The primary tumor site was the small intestine in 245 patients (38%) and pancreas in 194 patients (30%). With a median follow-up of 44 months, the median, 5 and 10 year OS for each treatment group was as follows: hepatic resection (n = 58, 9%), 160 months, 90%, 70%; radiofrequency ablation (n = 28, 4%), 123 months, 84%, 55%; chemoembolization (n = 130, 20%), 66 months, 55%, 28%; systemic therapy (n = 316, 49%), 70 months, 58%, 31%; and observation (n = 117, 18%), 38 months, 38%, 20%. Age [hazard ratio (HR) 1.0, p < 0.001), small bowel primary site (HR 0.5, p < 0.001), hepatic resection (HR 0.3, p = 0.001), well-differentiated tumors (HR 0.3, p < 0.001), alkaline phosphatase within normal limit (WNL) (HR 0.4, p < 0.001), and chromogranin A WNL (HR 0.5, p < 0.001) were significant independent prognosticators for OS. This series represents one of the largest single-institution studies of NELM reported. We found that hepatic resection was associated with highly favorable OS. Our observations support hepatic resection in appropriately selected patients.


Fragmented QRS on a 12-lead ECG: a predictor of mortality and cardiac events in patients with coronary artery disease.
Fragmented QRS (fQRS) on a 12-lead electrocardiogram (ECG) is associated with myocardial scar in patients with coronary artery disease (CAD). We postulated that fQRS is a predictor of cardiac events and mortality in patients who have known CAD or who are being evaluated for CAD. The cardiac events (myocardial infarction, need for revascularization, or cardiac death) and all-cause mortality were retrospectively reviewed in 998 patients (mean age 65.5 +/- 11.9 years, male 967) who underwent nuclear stress test. The fQRS on a 12-lead ECG included various RSR' patterns (> or =1 R' prime or notching of S wave or R wave) without typical bundle branch block in 2 contiguous leads corresponding to a major coronary artery territory. All-cause mortality (93 [34.1%] vs 188 [25.9%]) and cardiac event rate (135 [49.5%] vs 200 [27.6%]) were higher in the fQRS group compared with the non-fQRS group during a mean follow-up of 57 +/- 23 months. A Kaplan-Meier survival analysis revealed significantly lower event-free survival for cardiac events (P <.001) and all-cause mortality (P = .02). Multivariate Cox regression analysis revealed that significant fQRS was an independent significant predictor for cardiac events but not for all-cause mortality. The Kaplan-Meier survival analysis showed no significant difference between fQRS and Q waves groups for cardiac events (P = .48) and all-cause mortality (P = .08). The fQRS is an independent predictor of cardiac events in patients with CAD. It is associated with significantly lower event-free survival for a cardiac event on long-term follow-up.


Management of hypospadias cripples with two-staged Bracka's technique.
Patients labelled as 'hypospadias cripples' pose a challenge to reconstructive surgeons because of the complexity of the problem and limited options for reconstruction. The two-staged Bracka method is a versatile technique that is relatively easy to learn and applicable in difficult cases of salvage hypospadias. Over a period of 8 years, we applied this technique to 100 patients with hypospadias cripples who had previously undergone multiple (3-16) procedures. In the first stage, a full-thickness graft of skin or buccal mucosa was used for urethral plate reconstruction after release of chordee. Stage II was carried out at least 6 months after the first procedure. Meatal opening at the tip of the glans was achieved in 94 patients, straightening of the penis in 96 and proper urinary stream in 92 patients. Fistula formation occurred in nine patients. In our opinion, the two-staged Bracka technique is a useful strategy to deal with the myriad abnormalities encountered in crippled hypospadias. This technique not only creates a neourethra successfully, but also gives the penis a near-normal shape and appearance.


Recreational marathon running does not cause exercise-induced left ventricular hypertrabeculation.
Marathon running in novices represents a natural experiment of short-term cardiovascular remodeling in response to running training. We examine whether this stimulus can produce exercise-induced left ventricular (LV) trabeculation. Sixty-eight novice marathon runners aged 29.5 ± 3.2 years had indices of LV trabeculation measured by echocardiography and cardiac magnetic resonance imaging 6 months before and 2 weeks after the 2016 London Marathon race, in a prospective longitudinal study. After 17 weeks unsupervised marathon training, indices of LV trabeculation were essentially unchanged. Despite satisfactory inter-observer agreement in most methods of trabeculation measurement, criteria defining abnormally hypertrabeculated cases were discordant with each other. LV hypertrabeculation was a frequent finding in young, healthy individuals with no subject demonstrating clear evidence of a cardiomyopathy. Training for a first marathon does not induce LV trabeculation. It remains unclear whether prolonged, high-dose exercise can create de novo trabeculation or expose concealed trabeculation. Applying cut off values from published LV noncompaction cardiomyopathy criteria to young, healthy individuals risks over-diagnosis.


The assessment of normal and abnormal luteal function by transvaginal color Doppler sonography.
To evaluate intraovarian resistance index (RI) in 47 healthy fertile volunteers with ovulatory cycles, 28 patients with luteal phase defect (LPD) and four patients with luteinized unruptured follicle (LUF Sy). Transvaginal color Doppler assessment of the follicular and corpus luteum blood flow and plasma progesterone (P) levels were obtained in each patient. Significantly higher intraovarian artery RI (< 0.001) was obtained for LPD group than for controls during the luteal phase. In the control group both follicular and corpus luteum RI were significantly lower (P < 0.001) on the dominant side, while in LPD group no difference (P > 0.05) between the sides occurred. Mean P levels were significantly lower (P < 0.001) in the LPD group (6.9 +/- 2.3 ng/ml) than in controls (24.1 +/- 11.4 ng/ml). In all the LPD patients histopathology revealed delayed endometrial pattern, while normal endometrial dating was found in all the evaluated patients form the control group (n = 15). In the patients with LUF Sy (n = 4) similar RI values were obtained in the follicular and corpus luteum phase. There was no difference between the sides in terms of the intraovarian RI, while subnormal values of P were obtained in all the examined patients (14.1 +/- 6.2 ng/ml). Transvaginal color Doppler may predict the function capacity of the corpus luteum.


Trim58 degrades Dynein and regulates terminal erythropoiesis.
TRIM58 is an E3 ubiquitin ligase superfamily member implicated by genome-wide association studies to regulate human erythrocyte traits. Here, we show that Trim58 expression is induced during late erythropoiesis and that its depletion by small hairpin RNAs (shRNAs) inhibits the maturation of late-stage nucleated erythroblasts to anucleate reticulocytes. Imaging flow cytometry studies demonstrate that Trim58 regulates polarization and/or extrusion of erythroblast nuclei. In vitro, Trim58 directly binds and ubiquitinates the intermediate chain of the microtubule motor dynein. In cells, Trim58 stimulates proteasome-dependent degradation of the dynein holoprotein complex. During erythropoiesis, Trim58 expression, dynein loss, and enucleation occur concomitantly, and all are inhibited by Trim58 shRNAs. Dynein regulates nuclear positioning and microtubule organization, both of which undergo dramatic changes during erythroblast enucleation. Thus, we propose that Trim58 promotes this process by eliminating dynein. Our findings identify an erythroid-specific regulator of enucleation and elucidate a previously unrecognized mechanism for controlling dynein activity.


Assessment of lung function in children by cross-sectional imaging: techniques and clinical applications.
Imaging techniques are indispensable for diagnosis and follow-up of paediatric pulmonary diseases. In the past, interest was focused on morphological aspects of pulmonary tissue. With the development of novel CT and MRI techniques, functional pulmonary imaging became available. In this review, the new techniques of cross-sectional functional imaging of the lung are presented and the value of these methods for investigating paediatric pulmonary diseases and their potential clinical applications are discussed.


Dietary macronutrients do not differently affect postprandial vascular endothelial function in apparently healthy overweight and slightly obese men.
Well-designed trials comparing side-by-side effects of macronutrients on postprandial endothelial function are missing. Therefore, we investigated under well-controlled and isocaloric condition effects of fat, carbohydrates, and protein on postprandial endothelial function as assessed by brachial artery flow-mediated vasodilation (FMD), an important non-invasive technique to assess endothelial function. Eighteen apparently healthy overweight and slightly obese men (BMI 26.0-35.0 kg/m2) completed this randomized, double-blinded, cross-over trial. The study consisted of three test days each separated by a wash-out period of at least 1 week. After an overnight fast, men received an isocaloric meal providing 3987 kJ (953 kcal) that was either high in dietary fat (En% fat [F]/carbohydrates [C]/protein [P]: 52.3, 39.2, 8.0), carbohydrates (En% F/C/P: 9.6, 81.5, 8.6), or protein (En% F/C/P: 10.6, 51.5, 36.9). Fasting and 2-h postprandial FMD responses were measured. A postprandial decrease of 1.2% point in FMD was observed after the high-protein meal (P = 0.015). However, postprandial changes did not differ between meals (P = 0.45). An increase in baseline brachial artery diameters was observed after the high-protein meal (P < 0.001) and changes differed between meals (P = 0.020). A meal*time interaction was found for plasma glucose concentrations, with the most pronounced increases after the high-carbohydrate meal at T15, T30, T60, and T90 (P < 0.05). A significant time and meal (P < 0.001), but no time*meal effect (P = 0.06) was found for serum insulin concentrations. Increases in serum triacylglycerol concentrations did not differ between meals (P = 0.014). Macronutrients did not differently affect postprandial endothelial function in apparently healthy overweight and slightly obese men. Trial registration number (ClinicalTrials.gov) NCT03139890 in May 2017.


Molecular identification and phylogenetic relationship of Demodex mites based on mitochondrial 16S rDNA.
Demodex mites are tiny parasites that live around hair follicles of mammals. The two main species of Demodex i.e. Demodex folliculorum and Demodex brevis present in humans are found near the hair follicles of eyes. The present study was to understand the presence of Demodex mites in people suffering from blepharitis in Amritsar, Punjab. Demodex mites samples present in blepharitis patients were isolated from the eyelashes. DNA was isolated from three mites and used for PCR amplification of mitochondrial (mt) 16S rDNA. The amplified PCR product were purified and used for molecular identification. The amplified mt16s rDNA product was sequenced and subjected to BLAST search in the NCBI database for molecular identification. The identified mite belongs to Demodex folliculorum species. The phylogenetic tree constructed by using mt16s rDNA sequence suggests that D. folliculorum is closer to D. canis than to D. brevis. All the three isolates belong to D. folliculorum and the mitochondrial DNA 16S rDNA partial sequence is applicable for phylogenetic relationship analysis.


[Solitary necrotic nodule of the liver: about two cases].
Nodular liver lesions mainly consist of tumors. Solitary necrotic nodule of the liver is rare. Preoperative diagnosis is difficult. We report the case of a 43-year old woman undergoing surgery for the treatment of a rectal adenocarcinoma metastatized to the liver. Abdominal CT scan showed liver nodule mimicking liver metastasis. The second case is that of a 56 year-old man undergoing cholecystectomy in whom a liver nodule was detected intraoperatively. In both cases, liver nodule was subcapsular and was resected. Anatomopathological examination allowed the diagnosis of solitary necrotic nodule of the liver. Nonspecific necrotic nodule of the liver should be suspected in liver lesions, even in neoplastic context. Characterization using imaging studies and puncture biopsy of liver lesions can be useful.


Improving chronic illness self-management with the Apsáalooke Nation: Development of the Báa nnilah program.
Since 1996, members of the Apsáalooke (Crow) Nation and faculty and students at Montana State University have worked in a successful community-based participatory research (CBPR) partnership, leading to increased trust and improvements in health awareness, knowledge, and behaviors. As major barriers to health and healthy behaviors have caused inequities in morbidity and mortality rates for multiple chronic diseases among the Apsáalooke people, community members chose to focus the next phase of research on improving chronic illness management. Existing chronic illness self-management programs include aspects inconsonant with Apsáalooke culture and neglect local factors seen as vital to community members managing their health conditions. The aim of this study was to use CBPR methods grounded in Apsáalooke cultural values to develop an intervention for improving chronic illness self-management. Community members shared stories about what it is like to manage their chronic illness, including facilitators and barriers to chronic illness management. A culturally consonant data analysis method was used to develop a locally-based conceptual framework for understanding chronic illness management and an intervention grounded in the local culture. Components of the intervention approach and intervention content are detailed and similarities and differences from other chronic illness management programs are described. Our collaborative process and product may be helpful for other communities interested in using story data to develop research projects, deepen their understanding of health, and increase health equity.


Environmental analysis of fluorinated alkyl substances by liquid chromatography-(tandem) mass spectrometry: a review.
Fluorinated alkyl substances (FASs) are widely distributed contaminants that have been found in many environmental, human and biological samples throughout the world. Perfluorochemicals are used in many industry and consumer products, such as polymers and surfactants, because they have unique and useful properties (they are stable, chemically inert and generally unreactive). However, these compounds have also been found to be toxic, persistent and bioaccumulative. In recent years various analytical methods have been developed for the analysis of FASs in environmental samples. Most of these methods are based on liquid chromatography coupled to mass spectrometry (LC-MS) or tandem mass spectrometry (LC-MS/MS), since this is considered to be the technique of choice. This article reviews the various LC-(tandem)MS methods described so far for the analysis of FASs in water, sediment, sludge and biota samples. It discusses the main experimental conditions used for sample pretreatment and for analysis as well as the most relevant problems encountered and the limits of detection achieved.


Integrated adsorption and biological removal of the emerging contaminants ibuprofen, naproxen, atrazine, diazinon, and carbaryl in a horizontal tubular bioreactor.
Groundwater and surface water bodies may have contaminants from urban, industrial, or agricultural wastewater, including emerging contaminants (ECs) or micropollutants (MPs). Frequently, they are not efficiently removed by microbial action due to their minimal concentration in water and the low microbiota affinity for complex compounds. This work developed a process allowing the adsorption of contaminants and their simultaneous biodegradation using horizontal tubular fixed-bed biofilm reactors (HTR). Each HTR has two zones: an equalizer-aerator of the incoming liquid flow and a fixed bed zone. This zone was packed with a mixed support material consisting of granular bio-activated carbon (Bio-GAC) and porous material that increases the bed permeability, thus decreasing the pressure drop. Five microbial communities were acclimated and immobilized in granular activated carbon (GAC) to obtain different specialized Bio-GAC particles able to remove the micropollutants ibuprofen, naproxen, atrazine, carbaryl, and diazinon. The Bio-GAC particles were transferred to HTRs continuously run in microaerophilia at several MPs loading rates. Under these conditions, the removal efficiencies of MPs, except atrazine and carbaryl, were around 100.


A plastid organelle as a drug target in apicomplexan parasites.
Parasites of the phylum Apicomplexa include many important human and veterinary pathogens such as Plasmodium (malaria), Toxoplasma (a leading opportunistic infection associated with AIDS and congenital neurological birth defects), and Eimeria (an economically significant disease of poultry and cattle). Recent studies have identified an unusual organelle in these parasites: a plastid that appears to have been acquired by secondary endosymbiosis of a green alga. Here we show that replication of the apicomplexan plastid (apicoplast) genome in Toxoplasma gondii tachyzoites can be specifically inhibited using ciprofloxacin, and that this inhibition blocks parasite replication. Moreover, parasite death occurs with peculiar kinetics that are identical to those observed after exposure to clindamycin and macrolide antibiotics, which have been proposed to target protein synthesis in the apicoplast. Conversely, clindamycin (and functionally related compounds) immediately inhibits plastid replication upon drug application-the earliest effect so far described for these antibiotics. Our results directly link apicoplast function with parasite survival, validating this intriguing organelle as an effective target for parasiticidal drug design.


Inverse relationship between HIV-1 p24 antigenemia, anti-p24 antibody and neutralizing antibody response in all stages of HIV-1 infection.
A double blind cohort study was conducted on 149 homosexual males and 36 patients with AIDS to investigate the relationship between HIV-1 antigenemia, the presence of neutralizing antibody (NA) activity and specific anti-viral core protein (p24) antibody (Ab) in the sera of HIV infected individuals during their progression to AIDS. All AIDS patients and 68% (101/149) of the homosexual males were HIV seropositive upon entering the study. Of those 48 (32%) homosexuals who were HIV negative at the onset, three seroconverted during the two year observation period. Retrospective studies of the HIV(-) subjects' sequentially stored serum samples demonstrated an early transient appearance of gag encoded p24 antigen (Ag) which preceded their production of NA and specific anti-p24 Ab. Following their seroconversion, no more circulating p24 Ag could be detected. Among the 101 HIV positive homosexuals, 16% rapidly progressed to AIDS and seven of these 16 (44%) subjects eventually died during the two year observation period. In this group of individuals with poor prognosis, presence of NA and anti-p24 Ab commenced at the onset reaching peak levels just prior to developing AIDS and began to decline as the clinical course worsened. Their circulating level of p24 Ag remained undetectable as long as there was quantifiable NA and anti-p24 Ab in their sera. Reappearance of circulatory p24 Ag, on the other hand, was associated with high risk for progression to AIDS.2+hus, while only 11


Copulatory behavior and hypothalamic estrogen and progestin receptors in chronically insulin-deficient female rats.
The effects of relatively short- or long-term diabetes on sexual receptivity and and proceptivity and on hypothalamic estrogen and progestin receptors were examined in rats fed regular chow or high fat diet. Ovariectomized, streptozotocin-induced chronically insulin deficient and normal rats received sequential treatments with 2 micrograms estradiol benzoate (EB) and 1 mg progesterone (P) 10 days following the induction of diabetes and were tested for lordosis and soliciting behaviors. Nondiabetic rats fed either diet displayed significantly higher lordosis and solicitation behaviors than chow-fed diabetics, and fat-fed diabetic animals displayed behavior levels intermediate to those of nondiabetic and chow-fed rats. Ten days after the induction of diabetes, the levels of hypothalamic estrogen receptors of chow-fed diabetics were significantly lower than nondiabetics with the fat-fed diabetic group showing intermediate levels. However, 70 days after streptozotocin treatment diabetic rats had significantly lower estrogen receptors than nondiabetics regardless of the diet. Treatment of long-term (70 days) diabetic rats with 1-2 U of U-100 Lente insulin for 24 hr or 7 days was ineffective in restoring the hypothalamic estrogen receptor concentrations to those of nondiabetics. Three weeks following induction of diabetes, induction of cytoplasmic progestin receptors by EB treatment was significantly impaired in diabetic animals fed either chow or high fat diet. Although the reproductive dysfunctions present in short-term diabetic female rats may be due in part to chronic fuel deprivation, it appears that the long-term maintenance of cytosol estrogen receptor level is dependent on other actions of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)


The Hippo Signaling Transducer TAZ Regulates Mammary Gland Morphogenesis and Carcinogen-induced Mammary Tumorigenesis.
Hippo signaling pathway is an evolutionarily conserved pathway that controls organ size by regulating cell proliferation, apoptosis and stem cell self-renewal. TAZ (transcriptional coactivator with the PDZ-binding motif) is a key downstream effector of the mammalian Hippo pathway. Here, using a transgenic mouse model with mammary-gland-specific expression of constitutively active TAZ, we found that TAZ induction in mammary epithelial cells was associated with an increase in mammary glandular size, which probably resulted from adipocyte hypertrophy. Consistent with its known oncogenic potential, we observed tumor formation in TAZ transgenic mice after administration of the carcinogen 7,12-dimethylbenzanthracene (DMBA) and demonstrated that tumorigenesis was reliant on the presence of TAZ. Our findings establish a previously unknown roles of TAZ in regulating both mammary gland morphogenesis as well as carcinogen-induced mammary tumor formation.


Adsorption of anionic dyes on chitosan beads. 1. The influence of the chemical structures of dyes and temperature on the adsorption kinetics.
In this work, chitosan beads were synthesized in acidic medium and cross-linked in 1% glutaraldehyde solution. The characterization of the materials using TG/DTG, XRD, and BET surface areas showed that the beads did not modify their characteristics after the cross-linking reaction. The cross-linked beads were utilized as adsorbents for the removal of the yellow-, blue-, and red-anionic reactive dyes from aqueous solutions at pH 2.0. Adsorption of the yellow-dye increased from 25 to 50 degrees C. However, adsorption of the blue-dye decreased from 25 to 50 degrees C. Interestingly, the adsorption of the red-dye decreased from 25 to 35 degrees C and increased from 45 to 50 degrees C. The kinetic data were evaluated using an Avrami kinetic model, where the parameter n was related to the determination of changes in the adsorption mechanisms. Adsorption data of the dyes in relation to the contact time, the chemical structures of the dyes, and temperature were presented and were discussed.


Small bowel obstruction secondary to incomplete removal of a ventriculoperitoneal shunt: case report.
Small bowel obstruction and partial enteral loss secondary to entrapment by an incompletely removed ventriculoperitoneal shunt is a previously unreported hazard.


Intestinal microbiota in patients with chronic hepatitis C with and without cirrhosis compared with healthy controls.
The importance of the intestinal microbiota for the onset and clinical course of many diseases, including liver diseases like non-alcoholic steatohepatitis and cirrhosis, is increasingly recognized. However, the role of intestinal microbiota in chronic hepatitis C virus (HCV) infection remains unclear. In a cross-sectional approach, the intestinal microbiota of 95 patients chronically infected with HCV (n=57 without cirrhosis [NO-CIR]; n=38 with cirrhosis [CIR]) and 50 healthy controls (HC) without documented liver diseases was analysed. Alpha diversity, measured by number of phylotypes (S) and Shannon diversity index (H'), decreased significantly from HC to NO-CIR to CIR. S and H' correlated negatively with liver elastography. Analysis of similarities revealed highly statistically significant differences in the microbial communities between HC, NO-CIR and CIR (R=.090; P<1.0×10-6 ). Stratifying for HCV genotypes even increased the differences. In addition, we observed distinct patterns in the relative abundance of genera being either positive or negative correlated with diseases status. This study shows that not only the stage of liver disease but also HCV infection is associated with a reduced alpha diversity and different microbial community patterns. These differences might be caused by direct interactions between HCV and the microbiota or indirect interactions facilitated by the immune system.


Rational design of some substituted phenyl azanediyl (bis) methylene phosphonic acid derivatives as potential anticancer agents and imaging probes: Computational inputs, chemical synthesis, radiolabeling, biodistribution and gamma scintigraphy.
Bisphosphonates are widely used for treatment of osteoporosis. Recently, they have been reported to be effective anticancer agents. In this work, we designed some substituted phenyl (azanediyl) bis (methylene phosphonic acid) to be tested for their anticancer effect. Both molecular docking and dynamics studies were used to select the top ranked highly scored compounds. The selected hits showed potential in vitro anticancer effect against some cell lines. Biodistribution pattern and gamma scintigraphy were conducted to the most effective derivative (BMBP) after radiolabeling with 99mTc. Results of biodistribution and scintigraphic imaging of 99mTc-BMBP in tumor bearing mice showed a notable tumor affinity, and confirmed the targeting affinity of BMBP to the tumor tissues. As a conclusion, BMBP could act as potential anticancer agent and imaging probe.


Malignant (fibrous) histiocytoma arising in association with a bone infarct in sicle-cell disease: coincidence or cause-and-effect?
A patient with homozygous-S sickle-cell disease complicated by malignant (fibrous) histiocytoma arising within a tibial medullary infarct is reported. This is the ninth reported case of human sarcoma associated with bone infarct and the first associated with sickle-cell disease. Evidence for a causal relationship is presented.


Acute renal failure as the presenting feature of leukaemic infiltration in chronic lymphocytic leukaemia.
Chronic lymphocytic leukaemia (CLL) is a neoplastic condition of B cells which commonly affects the lymph nodes, liver, spleen and bone marrow. Leukaemic involvement of the kidney is also relatively common in CLL, but characteristically is not associated with renal impairment. Our report describes a patient who developed acute renal failure as the initial presenting feature of CLL. The renal failure was subsequently found to be due to direct leukaemic infiltration. Treatment with chlorambucil and prednisolone resulted in stabilisation of the renal function for approximately 1 year prior to the need for long-term haemodialysis. Leukaemic infiltration of kidney should always be considered when a patient with CLL presents with renal impairment, regardless of the clinical stage, as the renal failure often responds well to chemotherapy.


Dual-energy CT and its potential use for quantitative myocardial CT perfusion.
Application of quantitative myocardial CT perfusion (CTP) for the assessment of coronary artery disease may have a significant effect on patient care as the functional significance of a coronary stenosis can be evaluated through absolute measurement of the downstream myocardial perfusion (MP) both at rest and under exercise or pharmacologic stress. A main challenge of myocardial CTP is beam hardening (BH), arising from the polychromatic nature of x-rays used in CT scanning and the presence of highly attenuating contrast agent in the heart chambers during the CT acquisition. The BH effect induces significant nonuniform shifts in CT numbers which, if uncorrected, can lead to inaccurate assessment of MP. With the recent developments of dual-energy CT (DECT) scanning on clinical scanners, the BH effect on MP measurement could be reduced with the generation of monochromatic images relatively free of BH artifacts from the acquired dual-energy data. Here, we review the different techniques of acquiring dual-energy scans and generating monochromatic images, followed by discussion on the progress of developing a DECT technique with reduced radiation dose for quantitative myocardial CTP.


Effects of male partners upon proceptivity in ovariectomized estradiol-treated marmosets (Callithrix jacchus).
Effects of male partners upon the expression of female proceptivity were examined in two experiments using 16 ovariectomized marmosets. Experiment 1 showed that the female's proceptive tongue-flicking display (PTF) is triggered specifically by eye contact with the male. Stimulation of PTF by administration of estradiol-17 beta (E2) to ovariectomized females depends in part upon the male's responsiveness to female displays, such as "staring" and "freezing," which may serve to attract his attention and to establish eye contact. Experiment 2 provided evidence that females' proceptivity decreases if their male partners are lesioned in the preoptic area/anterior hypothalamus. Such males are sexually hypoactive and less responsive to the females' visual displays. However, E2 still activates PTF if females succeed in initiating eye contact with males. Results indicate that variability in effects of E2 upon proceptivity in marmosets may be influenced by subtle aspects of facial communication between the sexes as well as by individual differences in hormonal sensitivity. Copulatory activity in males is not essential for E2 to exert its stimulatory action upon proceptivity in female marmosets.


Dihydrotetramethylrosamine: a long wavelength, fluorogenic peroxidase substrate evaluated in vitro and in a model phagocyte.
Dihydrotetramethylrosamine, a fluorogenic substrate for peroxidase, and its fluorescent oxidation product, tetramethylrosamine chloride, were evaluated. The substrate is colorless and nonfluorescent while the oxidized dye absorbs at 550 nm and emits at 574 nm in both methanol and water. In vitro assays demonstrated that the substrate was oxidized to the fluorophore by horseradish peroxidase in the presence of hydrogen peroxide. In vivo uptake and oxidation of the substrate by Amoeba proteus was characterized by the initial appearance of fluorescent phagocytic vacuoles with subsequent localization in vesicular organelles the size and shape of protozoan mitochondria. Similar staining patterns occurred in cells incubated with substrate, oxidized rosamine or rhodamine 123, a known mitochondrial stain.


IgG subclass of anti-HSV antibodies following neonatal HSV infections.
Ten survivors of neonatal HSV encephalitis had IgG1 and IgG3 antibodies to HSV 6 or more months after their infection. Six had IgG4 antibodies but only one had IgG2 antibodies. Titers of anti-HSV antibodies were similar following neonatal and later HSV infections. Antibody deficiency is thus not part of the selective deficiency of HSV-specific immunity following neonatal infection.


Terminally Ill Cancer Patients' Emotional Preparedness for Death Is Distinct From Their Accurate Prognostic Awareness.
Emotional preparedness for death (hereafter called death preparedness) and prognostic awareness (PA), a distinct but related concept, each contributes to patients' practical, psychological, and interpersonal preparations for death. However, the distinction between these two concepts has never been investigated. To evaluate the distinction between death preparedness and accurate PA by examining their agreement during cancer patients' last year and the similarity of their predictors. For this secondary analysis of a longitudinal study of death preparedness for 277 patients with cancer, agreement between death preparedness and accurate PA was evaluated by percentages and kappa coefficients, and predictors of the two outcomes were evaluated by multivariate logistic regression models with the generalized estimating equation. Levels of agreement between reported death preparedness and accurate PA increased slightly (42.44%-52.85%) from 181-365 days to one to 30 days before death, with kappa values from -0.190 (-0.319, -0.061) to -0.006 (-0.106, 0.093), indicating poor agreement. Participants who were male, older, reported financial sufficiency, had fewer distressing symptoms, and perceived higher levels of social support were more likely to report death preparedness. Participants who were female, had greater than high-school educational attainment, and endured higher levels of functional dependence were more likely to report accurate PA. The distinction between death preparedness and accurate PA was supported by their poor agreement, lack of reciprocal associations, and two different sets of predictors. Health care professionals should not only cultivate cancer patients' accurate PA but also facilitate emotional preparation for death to achieve a good death and improve end-of-life care quality.


Public values and plurality in health priority setting: What to do when people disagree and why we should care about reasons as well as choices.
'What does 'The Public' think?' is a question often posed by researchers and policy makers, and public values are regularly invoked to justify policy decisions. Over time there has been a participatory turn in the social and health sciences, including health technology assessment and priority setting in health, towards citizen participation such that public policies reflect public values. It is one thing to agree that public values are important, however, and another to agree on how public values should be elicited, deliberated upon and integrated into decision-making. Surveys of public values rarely deliver unanimity, and preference heterogeneity, or plurality, is to be expected. This paper examines the role of public values in health policy and how to elicit, analyse, and present values, in the face of plurality. We delineate the strengths and weaknesses of aggregative and deliberative methods before setting out a new empirical framework, drawing on Sunstein's Incompletely Theorised Agreements, based on three levels: principles, policies and patients. The framework is illustrated using a recognised policy dilemma - the provision of high cost, limited-effect medicines intended to extend life for people with terminal illnesses. Application of the multi-level framework to public values permits transparent consideration of plurality, including analysis of coherence and consensus, in a way that offers routes to policy recommendations that are based on public values and justified in those terms. Using the new framework and eliciting quantitative and qualitative data across levels of abstraction has the potential to inform policy recommendations grounded in public values, where values are plural. This is not to suggest that one solution will magically emerge, but rather that choices between policies can be explicitly justified in relation to the properties of public values, and a much clearer understanding of (in)consistencies and areas of consensus.


The gas-phase ozonolysis of α-humulene.
α-Humulene contains three double bonds (DB), and after ozonolysis of the first DB the first-generation products are still reactive towards O(3) and produce second- and third-generation products. The primary aim of this study consisted of identifying the products of the three generations, focusing on the carboxylic acids, which are known to have a high aerosol formation potential. The experiments were performed in a 570 litre spherical glass reactor at 295 K and 730 Torr. Initial mixing ratios were 260-2090 ppb for O(3) and 250-600 ppb for α-humulene in synthetic air. Reactants and gas-phase products were measured by in situ FTIR spectroscopy. Particulate products were sampled on Teflon filters, extracted with methanol and analyzed by LC-MS/MS-TOF. Using cyclohexane (10-100 ppm) as an OH-radical scavenger and by monitoring the yield of cyclohexanone by PTR-MS, an OH-yield of (10.5 ± 0.7)% was determined for the ozonolysis of the first DB, and (12.9 ± 0.7)% of the first-generation products. The rate constant of the reaction of O(3) with α-humulene is known as k(0) = 1.17 × 10(-14) cm(3) molecule(-1) s(-1) [Y. Shu and R. Atkinson, Int. J. Chem. Kinet., 1994, 26, 1193-1205]. The reaction rate constants of O(3) with the first-generation products and the second-generation products were, respectively, determined as k(1) = (3.6 ± 0.9) × 10(-16) and k(2) = (3.0 ± 0.7) × 10(-17) cm(3) molecule(-1) s(-1) by Facsimile-simulation of the observed ozone decay by FTIR. A total of 37 compounds in the aerosol phase and 5 products in the gas phase were tentatively identified: 25 compounds of the first-generation products contained C13-C15 species, 9 compounds of the second-generation products contained C8-C11 species, whereas 8 compounds of the third-generation products contained C4-C6 species. The products of all three generations consisted of a variety of dicarboxylic-, hydroxy-oxocarboxylic- and oxo-carboxylic acids. The formation mechanisms of some of the products are discussed. The residual FTIR spectra indicate the formation of secondary ozonides (SOZ) in the gas phase, which are formed by the intramolecular reaction of the Criegee moiety with the carbonyl endgroup. These SOZ revealed to be stable over several hours and its formation was shown not to be affected by the addition of Criegee-radical scavengers such as HCOOH or H(2)O. This suggests that in the ozonolysis of α-humulene at atmospheric pressures the POZ will decompose rapidly, and that a large fraction of the formed exited Criegee Intermediate will be stabilized to form stable SOZ, while the formation of OH-radicals via the hydroperoxide channel will be a minor process.


Interrupted time series design to evaluate ICD-9-CM to ICD-10-CM coding changes on trends in Colorado emergency department visits related to traumatic brain injury.
The transition in 2015 to the Tenth Revision of the International Classification of Disease, Clinical Modification (ICD-10-CM) in the US led the Centers for Disease Control and Prevention (CDC) to propose a surveillance definition of traumatic brain injury (TBI) utilizing ICD-10-CM codes. The CDC's proposed surveillance definition excludes "unspecified injury of the head," previously included in the ICD-9-CM TBI surveillance definition. The study purpose was to evaluate the impact of the TBI surveillance definition change on monthly rates of TBI-related emergency department (ED) visits in Colorado from 2012 to 2017. The monthly rate of TBI-related ED visits was 55.6 visits per 100,000 persons in January 2012. This rate in the transition month to ICD-10-CM (October 2015) decreased by 41 visits per 100,000 persons (p-value < 0.0001), compared to September 2015, and remained low through December 2017, due to the exclusion of "unspecified injury of head" (ICD-10-CM code S09.90) in the proposed TBI definition. The average increase in the rate was 0.33 visits per month (p < 0.01) prior to October 2015, and 0.04 visits after. When S09.90 was included in the model, the monthly TBI rate in Colorado remained smooth from ICD-9-CM to ICD-10-CM and the transition was no longer significant (p = 0.97). The reduction in the monthly TBI-related ED visit rate resulted from the CDC TBI surveillance definition excluding unspecified head injury, not necessarily the coding transition itself. Public health practitioners should be aware that the definition change could lead to a drastic reduction in the magnitude and trend of TBI-related ED visits, which could affect decisions regarding the allocation of TBI resources. This study highlights a challenge in creating a standardized set of TBI ICD-10-CM codes for public health surveillance that provides comparable yet clinically relevant estimates that span the ICD transition.


On the significance of subterritories in the "accumbens" part of the rat ventral striatum.
Although many workers have appreciated the striking cytologic and neurochemical similarities of neostriatum, accumbens and olfactory tubercle, a compelling case for regarding these areas as territories in a striatal complex awaited the arguments made by Heimer and his colleagues based on their investigations of connections. A number of recent papers support this viewpoint and extend it with the characterization of three accumbal subterritories: core, shell and rostral pole. The case for separate classifications of systems traversing the accumbens has become more compelling with each study that demonstrates connectional, cytoarchitectural and neurochemical specificity conforming to the boundaries separating the core and its downstream targets from the shell and its projection fields. Furthermore, its apparent composite of core-like and shell-like characteristics distinguishes the rostral pole as yet another unique subterritory. Differences in compartmental organization distinguish the accumbens and neostriatum. The available data are consistent with the periventricular and rostrolateral enkephalin-rich zones being ventralmost parts of the neostriatal patch and matrix compartments, respectively. The accumbal cell cluster compartment, on the other hand, appears to be a separate entity, with connectional and neurochemical features that are dissimilar to both patch and matrix of neostriatum. Boundaries between the accumbens and caudate-putamen remain elusive, and the point of view that such boundaries do not exist but, rather, are represented by "transition zones" must to a large degree reflect the reality. Likewise, it is important to acknowledge that the boundaries between accumbal subterritories are not necessarily distinct or observed faithfully by all of the afferent systems. "Transition zones" appear to be particularly significant organizational features in rostral and lateral parts of the accumbens. Interestingly, histochemically distinct cell clusters tend to be numerous in boundary regions between adjacent territories and subterritories. The predominant organizational pattern appears to be one in which the core, shell and rostral pole engage different forebrain systems that possibly subserve entirely different functions mediated by distantly related mechanisms. In this regard, it is of paramount interest that the processing of information conveyed to the accumbens by diverse cortical and subcortical inputs occurs within distinct and perhaps very different dopaminergic environments in the core, shell and rostral pole (e.g., see Refs 24, 34, 90, 110).


Microemulsion and diafiltration approaches: an attempt to maximize the global yield of DNA-loaded nanospheres.
The yield of DNA-loaded nanospheres in its widest definition includes encapsulation efficiency and the integrity of the loaded molecules plus the production yield of fabricated nanospheres. The former aspect could be considerably improved by adopting the microemulsion concept to enhance the stability of the primary emulsion during the preparation of nanospheres by the double emulsion solvent-removal method. The droplet size of the mentioned emulsion was monitored by means of photon electron correlation spectroscopy and could serve as an index for emulsion fineness and stability. DNA stability as a function of applied mechanical stress was monitored by horizontal agarose gel electrophoresis. The impact of the primary emulsion on nanosphere porosity was assessed as well. Regarding the second aspect of the global yield of nanospheres, i.e. production yield, a modified diafiltration technique was adopted for the washing and recovery processes in comparison with the traditional and for the conservation of particle size characteristics of the recovered nanospheres.