Rectal suppository insertion: the reliability of the evidence as a basis for nursing practice.
This paper considers the correct method for inserting a rectal suppository, both as a medication and also to achieve bowel evacuation. The aim is to find out whether the correct method is blunt end or pointed end foremost. It follows from a question raised by a third year student nurse. In the classroom, she had been taught that the correct method for the administration of a suppository for systemic absorption was to insert it blunt end foremost into the rectum. However, if the suppository was to be used for evacuant purposes, it should be given pointed end foremost. In clinical practice, however, she was told the suppository should always be inserted pointed end foremost in all cases, whatever the purpose. This article seeks to clarify the dilemma by examining the sources of evidence underpinning different methods for inserting a rectal suppository. Hence, the literature on the insertion of rectal suppositories was gathered as systematically as possible from medical journals and textbooks, nursing journals and textbooks and manufacturers' information to patients. Having gathered the literature, this was examined, appraised and critically analysed for rigour, coherence and reliability. The review of the literature appears to show that evidence adduced for inserting the suppository blunt end foremost derives from one study published in the Lancet in 1991, which challenged 'commonsense'. There did not appear to be other, more recent research. On the other hand, manufacturers' information to patients states generally that the suppository should be inserted pointed end foremost. This has direct relevance for the administration of suppositories and also raises questions as to how research may become integrated into healthcare practice without adequate justification. An article published in the Lancet in 1991 has had a fundamental effect on nursing practice, but has not been subject to scrutiny. The advice given in this Lancet article differs from that currently given by most manufacturers of suppositories, which involves the terms of their product licence. Hence, there is a potential for problems with legal liability should an untoward event arise. Inserting rectal suppositories, whether as a medication or to achieve bowel evacuation, is a very common healthcare practice. Currently, there is inconsistency and discrepancy in the correct method for this procedure in both nursing education and practice. This paper examines the reliability of existing evidence and shows the need for further work in order to provide a reliable evidence base for this commonplace clinical procedure.


Physiological Effects of Visual Stimulation with Forest Imagery.
This study was aimed to clarify the physiological effects of visual stimulation using forest imagery on activity of the brain and autonomic nervous system. Seventeen female university students (mean age, 21.1 ± 1.0 years) participated in the study. As an indicator of brain activity, oxyhemoglobin (oxy-Hb) concentrations were measured in the left and right prefrontal cortex using near-infrared time-resolved spectroscopy. Heart rate variability (HRV) was used as an indicator of autonomic nervous activity. The high-frequency (HF) component of HRV, which reflected parasympathetic nervous activity, and the ratio of low-frequency (LF) and high-frequency components (LF/HF), which reflected sympathetic nervous activity, were measured. Forest and city (control) images were used as visual stimuli using a large plasma display window. After sitting at rest viewing a gray background for 60 s, participants viewed two images for 90 s. During rest and visual stimulation, HRV and oxy-Hb concentration in the prefrontal cortex were continuously measured. Immediately thereafter, subjective evaluation of feelings was performed using a modified semantic differential (SD) method. The results showed that visual stimulation with forest imagery induced (1) a significant decrease in oxy-Hb concentrations in the right prefrontal cortex and (2) a significant increase in perceptions of feeling "comfortable," "relaxed," and "natural."


Effect of profound suppression of luteinizing hormone during treatment with gonadotrophin-releasing hormone analogue and purified follicle stimulating hormone upon development of cryopreserved embryos.
In response to previously published evidence from monkeys, this study examined the influence of the degree of luteinizing hormone (LH) suppression during the follicular phase of the stimulation cycle, upon cryopreserved embryo survival and development. The LH concentration of the mid-follicular phase was assessed in 250 in-vitro fertilization (IVF) cycles treated with gonadotrophin-releasing hormone analogue (GnRHa) and either purified follicle stimulating hormone (FSH) or human menopausal gonadotrophin (HMG), and was related to the performance of cryopreserved embryos in 351 subsequent embryo transfer cycles. Rates of embryo survival, embryo development rates, implantation rates, and pregnancy rates were examined with respect to the LH concentration recorded in the mid-follicular phase. In contrast to experimental evidence from other primates, there was no significant influence of the follicular phase LH concentration upon any of the parameters examined.


Prevention of emergence agitation in seven children receiving low-dose ketamine and propofol total intravenous anesthesia.
Emergence agitation (EA) can be a distressing side effect of pediatric anesthesia. We retrospectively reviewed the records of 7 pediatric oncology patients who received low-dose ketamine in conjunction with propofol for total intravenous anesthesia (TIVA) repeatedly for radiation therapy. EA signs were observed in all 7 patients in association with propofol TIVA but did not recur in any of 123 subsequent anesthetics sessions during which low-dose ketamine was added to propofol. Based on this experience, we suggest that low-dose ketamine added to propofol may be associated with prevention of EA in children with a history of EA with propofol TIVA.


A preliminary evaluation of next-generation sequencing as a screening tool for targeted genotyping of erythrocyte and platelet antigens in blood donors.
Matching the compatibility of donor blood with the recipient's antigens prevents alloimmunisation. Next-generation sequencing (NGS) technology is a promising method for extensive blood group and platelet antigen genotyping of blood donors. It circumvents the limitations of detecting known alleles based on predefined polymorphisms and enables targeted sequencing on a massive scale. The aim of this study was to evaluate the NGS AmpliSeq application on the Ion Torrent platform as a screening tool for genotyping blood donors' erythrocyte/platelet antigens. Primers for regions encoding antigens RhD (exons 5, 7), Rhc, RhE/e, Fya/b, Jka/b, M/N, S/s, HPA-1, 2, 3, 5, 15 were designed with Ion AmpliSeq Designer with manual inclusion of RHCE*C primers. DNA libraries of 57 regular blood donors with determined phenotype/genotype (prepared using the Ion AmpliSeq Library Kit and 14 primer pairs) were sequenced on the Ion Torrent PGM using 316v2 chips and 200 bp chemistry. Sequencing was successful in all but the MN and HPA-5 regions. Mean sequencing coverage in one experiment was 4,606 reads, except for the RHCE*C region (mean 568 reads). NGS results agreed with the known phenotype/genotype of donors except in one phenotypically Fy(a+b-) case in whom FY*A/FY*B alleles were found. Reading rates for homozygotes were 97-100%, while they were around 50% for heterozygotes. NGS of RHD regions led to identification of mutations in two RhD negative donors. NGS can be performed as a screening test to determine erythrocyte/platelet antigens in blood donors. This method allowed testing of 48 donors for 14 features (200 bp long) with the depth of a few thousand reads simultaneously, and the estimation of natural chimerism or hemi/homozygotic status. NGS screening can be adjusted to the genetic background of a given tested population.


A generalized arterial transfer function derived at rest underestimates augmentation of central pressure after exercise.
Peripheral exercise blood pressure and resting central blood pressure are considered more relevant to cardiovascular health than resting peripheral blood pressure. Central exercise blood pressure may well be an even more useful measure, but there is no simple non-invasive means of determining it. The aim of the present study was to establish whether the estimation of central blood pressure from peripheral blood pressure using a transfer function derived at rest, would hold after aerobic exercise. Thirty healthy young men were studied before and immediately (< 1 min) and 10 min after 15 min bicycle exercise at 65-70% of maximum heart rate. Simultaneous carotid and radial artery waveforms were recorded, and radial-to-carotid generalized transfer functions (GTF) were calculated using Fourier analysis for rest and immediately postexercise. Central systolic blood pressure (SBP) and augmentation index (AIx) were calculated for measured and derived waves. The resting GTF underestimated central SBP and AIx immediately (-5.8 +/- 2.1 mmHg, P = 0.01; -8.3 +/- 2.9%, P = 0.008) and 10 min after (-2.0 +/- 0.7 mmHg, P = 0.008; -7.0 +/- 2.1%, P = 0.003) exercise. No significant bias was found between measured and derived (using resting GTF) carotid values at rest. The use of an exercise-specific GTF resulted in no specific bias immediately or 10 min after exercise, although it overestimated blood pressure and AIx at rest (2.5 +/- 1.0 mmHg, P = 0.02; 11.3 +/- 3.0%, P = 0.001). A peripheral-to-central arterial GTF derived at rest significantly underestimates key measures of central arterial pressure immediately after exercise, and pressure estimations may be improved by the use of an exercise-specific GTF.


Screening for triploidy by the risk algorithms for trisomies 21, 18 and 13 at 11 weeks to 13 weeks and 6 days of gestation.
To examine the effectiveness in screening for triploidy at 11 weeks to 13 weeks and 6 days of gestation by the combined use of the risk algorithms for trisomies 21, 18 and 13 based on maternal age, fetal nuchal translucency (NT) thickness, fetal heart rate (FHR) and maternal serum free beta-hCG and PAPP-A. Prospective screening for trisomy 21, including 56 376 normal singleton pregnancies and 31 cases with triploidy (24 digynic and 7 diandric). Patient-specific risks for trisomies 21, 18 and 13 were calculated by multiplying the age related risk for trisomies 21, 18 and 13 with the likelihood ratio (LR) for fetal NT and with a combined LR for FHR, free beta-hCG and PAPP-A, respectively. Detection rates (DRs) and false positive rates (FPRs) for triploidy were calculated by taking the proportion with risks above a given risk threshold and standardized for maternal age according to the distribution of pregnancies in England and Wales in 2000 to 2002. In digynic triploidy, free beta-hCG was 0.16 (range 0.02-0.95) MoM and PAPP-A was 0.06 (range 0.02-0.47) MoM and the respective values for diandric triploidy were 8.74 (range 2.83-47.0) and 0.74 (range 0.32-1.51) MoM. Use of the trisomy 21 algorithm identified 5 of the 7 diandric cases and 3 of the 24 digynic ones at a 3% FPR. Combined use of the risk algorithms for trisomies 18 and 13 identified 20 of the 24 cases with the digynic triploidy at the FPR of 0.2%. When screen positivity was defined by a 3% FPR using the algorithm for trisomy 21 and an additional 0.2% FPR using the algorithms for trisomies 18 and 13, the total FPR was 3.1% and the DR was 84%. A beneficial side-effect of first trimester combined screening for trisomies is the detection of a high proportion of fetuses with triploidy.


Does mixing pancreatic enzyme microspheres (Pancrease) with food damage the enteric coating?
Supplemental pancreatic enzymes are required for the treatment of malabsorption associated with cystic fibrosis. It is a general practice for enzymes to be sprinkled on, or administered in, food given to infants or children who require pancreatic enzyme replacement. We tested the effect of in vitro incubation of enteric-coated pancreatic enzyme microspheres with infant foods on total recoverable enzyme activity and on the enteric coating. Incubation of enzyme beads with foods with pH greater than 5 (i.e., chicken pH 6.5, veal pH 6.3, and green beans pH 5.6) was without significant effect on either parameter. There was a statistically significant, albeit minor, reduction in maximum enzyme activity recovered following incubation with applesauce (pH 3.5). In addition, the thickness of the enteric coating was significantly reduced. Whether changes in the enzyme beads results in improved or diminished efficiency of therapy remains to be determined. Lipase, unprotected by enteric coating, was rapidly inactivated in applesauce, emphasizing the need to instruct parents about which foods to avoid when administering pancreatic enzymes without enteric coating.


Activated macrophages in human periodontitis.
Fifteen patients, eight males and seven females, ranging from 30 to 88 years of age with advanced periodontal disease were selected for this study. Biopsies and blood samples were taken of both normal and inflamed gingival tissues, and processed for detection of nonspecific esterase and acid phosphatase activity in monocytes and macrophages. Activated macrophages, as indicated by their intense reaction to acid phosphatase and nonspecific esterase, were found in the gingival epithelium, lamina propria, perivascular tissues and in the blood vessels in human chronic periodontitis. Blood smears of monocytes showed variability of stain intensity suggesting that their activation occurred in blood vessels where they marginate and emigrate into the perivascular tissues in chronic periodontitis. They then appear as macrophages that migrate through the connective tissue, penetrate the basement membrane and continue through the epithelium. The nonspecific esterase stain identified T-cells, by a singular dot-like granule, and plasma cells by multiple granules in the cytoplasm. Lymphocytes containing multiple cytoplasmic nonspecific esterase positive granules commonly were found only in the perivascular connective tissue and may represent B-cell differentiation to plasma cells. The plasma cell predominance, the presence of T-cells and activated macrophages indicated both humoral and cell-mediated responses are operative in human chronic periodontitis.


[SF-36 and the development of new assessment tools for quality of life].
The use of assessment tools for quality of life has allowed the incorporation of the views of patients in health decision-making. This article presents the characteristics and changes experienced by one of the most used questionnaires of quality of life at present the Short Form 36-item Health Survey SF-36 . We also discuss the issues related to the construction properties and applications of this measuring tool and other derived measures as the SF-12 the SF-8 the Dynamic Health Assessment DYNHA and the SF-6D. We emphasize the use of the SF-36 for assessing the effectiveness of interventions in health the SF-12 for the tracking of health disorders the SF-8 for the monitoring of population health the DYNHA for individualized evaluations in clinical practice and the SF-6D for economic analysis in health. Information on the versions validated for Portuguese language and the permission to use the questionnaires are provided.


A preliminary study on the induction of dioestrous ovulation in the mare--a possible method for inducing prolonged luteal phase.
Strong oestrous symptoms in the mare can cause problems with racing, training and handling. Since long-acting progesterone treatment is not permitted in mares at competition (e.g. according to FEI rules), there is a need for methods to suppress unwanted cyclicity. Spontaneous dioestrous ovulations in the late luteal phase may cause a prolongation of the luteal phase in mares. In this preliminary study, in an attempt to induce ovulation during the luteal phase, human chorionic gonadotropin (hCG) (3000 IU) was injected intramuscularly in four mares (experimental group) in the luteal phase when a dioestrous follicle > or = 30 mm was detected. A fifth mare included in this group was not treated due to no detectable dioestrous follicles > or = 30 mm. Four control mares were similarly injected with saline. The mares were followed with ultrasound for 72 hours post injection or until ovulation. Blood samples for progesterone analysis were obtained twice weekly for one month and thereafter once weekly for another two to four months. Three of the hCG-treated mares ovulated within 72 hours after treatment and developed prolonged luteal phases of 58, 68 and 82 days respectively. One treated mare never ovulated after the hCG injection and progesterone levels fell below 3 nmol/l nine days post treatment. Progesterone levels in the control mares were below 3 nmol/l within nine days after saline injection, except for one mare, which developed a spontaneously prolonged luteal phase of 72 days. HCG treatment may be a method to induce prolonged luteal phases in the mare provided there is a dioestrous follicle > or = 30 mm that ovulates post-treatment. However, the method needs to be tested on a larger number of mares to be able to draw conclusions regarding its effectiveness.


The organization of retinal maps within the dorsal and ventral lateral geniculate nuclei of the rabbit.
The cytoarchitectonic subdivisions in the rabbit's dorsal and ventral lateral geniculate nuclei have been related to the several retinal maps that can be defined in terms of the distribution of retinal axons within these nuclei. Destruction of different retinal sectors was combined with intravitreal injections of 3H-proline, so that the distribution of fiber degeneration and autoradiographic label in the geniculate nuclei could be used to define the retinal maps in each nucleus, and to compare the two nuclei with each other. The two nuclei show surprisingly similar patterns of organization. Each is made up of a laminated alpha sector that curves around a relatively cell-sparse beta sector. Two morphologically distinct layers of each alpha sector receive contralateral retinal afferents and between these there is a small region in receipt of ipsilateral afferents. In each nucleus, the lines of projection that represent single points in visual space pass perpendicular to the layers of the alpha sector and continue an almost straight course into the beta sector. Quantitative comparisons of the retinal maps show that the relative volumes devoted to the representation of segments of the visual field are approximately the same in the two nuclei.


Prevalence of Anxiety Symptoms and Associated Clinical and Sociodemographic Factors in Mexican Adults Seeking Psychological Support for Grief During the COVID-19 Pandemic: A Cross-Sectional Study.
The COVID-19 pandemic is one of the greatest challenges in modern history, with more than four million confirmed deaths worldwide. To date, evidence regarding the psychological impact of the COVID-19 pandemic on grievers is scarce for developing countries such as Mexico. This study aimed to assess the levels of anxiety and associated concerns in a sample of Mexican adults bereaved during the COVID-19 outbreak. A cross-sectional study was conducted through the Duelo COVID (COVID Grief) platform, which is a self-guided online treatment. A total of 5,224 participants reported their anxiety, depression, sleep quality, avoidance, and arousal, prolonged grief symptoms, and medication consumption. Independent sample Mann-Whitney U-tests, chi-square tests, and Kruskal-Wallis tests, as well as multinomial logistic regression, were conducted. Results indicated that 90.4% of the participants reported clinical levels of anxiety, depression, and sleep affectations. The people who lost someone during the last 5 months scored higher in normal grief symptoms compared to the people whose loss was 6 months ago or more, and 9.8% of individuals reported the use of prescription medication, with anxiolytics and antidepressants being the most common. Females, younger respondents, unemployed people with a lower educational level, and participants who disclosed a recent suicide attempt were among those who reported medication consumption. Sleep problems were more frequent in older participants.


Enhanced Average Thermoelectric Figure of Merit of the PbTe-SrTe-MnTe Alloy.
Thermoelectric properties of Na-doped PbTe-SrTe system have been improved by the addition of Mn. The substitution of Mn for Pb modifies the band structure of the PbTe-SrTe alloy, which enlarges the band gap and increases the valence band degeneracy. This leads to increased thermopowers and power factors near room temperature, and the electronic contribution to the total thermal conductivity is also substantially reduced due to increased resistivity. Moreover, alloying of MnTe within the PbTe matrix introduces low angle grain boundaries, and significantly reduces the lattice thermal conductivity due to the dislocation scattering. A thermoelectric figure of merit as high as 1.98 and an enhancement of the average thermoelectric figure of merit by 18% are achieved for the sample with 4 at% Mn with respect to the Mn-free sample, which can be mainly attributed to the synergistic effects of the band structure modification and the dislocation scattering on phonon transport, both induced by alloying with MnTe. Our experimental results demonstrate the promising potential of PbTe-SrTe-MnTe system for the application of waste heat recovery.


Investigating the effects of commercial probiotics on broiler chick quality and production efficiency.
A study was undertaken to test the effect of 2 commercially available probiotics on the production efficiency of broiler chickens hatched from the same breeder flock at 3 different ages (28, 43, and 57 wk). At each of the 3 breeder flock ages, 1,600 broiler chickens were hatched and randomly allocated to 1 of 4 treatments: 1) no probiotics (control), 2) probiotic 1 administered in the drinking water, 3) probiotic 1 administered as a spray, and 4) probiotic 2 administered in the feed. A coccidiostat was included in the feed, but no other antimicrobial agents were given. Broilers were then reared on straw litter in identical floor pens for a period of 6 wk. There were no significant differences in broiler BW, feed conversion, or mortality between the probiotic treatments and the control group in any of the trials. The 43-wk-old breeder flock had the highest fertility and hatchability and the lowest percentage of chicks culled at hatching. Throughout the broiler production period, the broilers from the 43- and 57-wk-old breeder flocks had higher BW and weight gains than the broilers produced at 28 wk of breeder flock age. Broiler feed conversion over the 6-wk production period decreased as the breeder flock aged. Probiotics had no effect on chick quality or production efficiency in broilers produced by the breeder flock ages examined.


Progress in Composite Hydrogels and Scaffolds Enriched with Icariin for Osteochondral Defect Healing.
Osteochondral structure reconstruction by tissue engineering, a challenge in regenerative medicine, requires a scaffold that ensures both articular cartilage and subchondral bone remodeling. Functional hydrogels and scaffolds present a strategy for the controlled delivery of signaling molecules (growth factors and therapeutic drugs) and are considered a promising therapeutic approach. Icariin is a pharmacologically-active small molecule of prenylated flavonol glycoside and the main bioactive flavonoid isolated from Epimedium spp. The in vitro and in vivo testing of icariin showed chondrogenic and ostseoinductive effects, comparable to bone morphogenetic proteins, and suggested its use as an alternative to growth factors, representing a low-cost, promising approach for osteochondral regeneration. This paper reviews the complex structure of the osteochondral tissue, underlining the main aspects of osteochondral defects and those specifically occurring in osteoarthritis. The significance of icariin's structure and the extraction methods were emphasized. Studies revealing the valuable chondrogenic and osteogenic effects of icariin for osteochondral restoration were also reviewed. The review highlighted th recent state-of-the-art related to hydrogels and scaffolds enriched with icariin developed as biocompatible materials for osteochondral regeneration strategies.


Effect of Sox10 on remyelination of the hippocampus in cuprizone-induced demyelinated mice.
The low number of oligodendrocytes (OLs) in the hippocampus of patients with schizophrenia suggests that hippocampal demyelination is changed in this condition. Sox10 is expressed throughout OL development. The effect of Sox10 on myelin regeneration is unknown. This study aimed to analyze changes in Sox10 expression in the hippocampus and its regulatory role in hippocampal myelin regeneration in a mouse model of demyelination. Mice were fed 0.2% cuprizone (CPZ) for six weeks to establish the acute demyelinating model (CPZ mice). Behavioral changes of these mice were assessed via open field and tail suspension tests. The ultrastructure of the myelin sheaths in the hippocampus was observed by transmission electron microscopy. The expression levels of myelin sheath-related proteins and the transcription factor Sox10 were detected via immunohistochemistry and Western blots. Furthermore, Sox10-overexpressing adeno-associated virus was injected into the hippocampus after establishing the demyelinating model to investigate effects of Sox10 on remyelination. CPZ mice showed abnormal behavioral changes, a large number of pathological changes in the myelin sheaths, and significantly reduced protein expression of the myelin sheath markers myelin basic protein and proteolipid protein. This confirmed that the demyelinating model was successfully established. Meanwhile, the protein expression of the oligodendrocyte precursor cell marker neural/glial antigen 2 (NG2) increased, whereas Sox10 expression decreased. After Sox10 overexpression in the hippocampus, the abnormal behavior was improved, the ultrastructure of the myelin sheaths was restored, and the expression of myelin sheath protein was reversed. NG2 expression was upregulated. Overexpression of Sox10 promotes hippocampal remyelination after CPZ-induced acute demyelination.


Multiplatform Metabolomics Characterization Reveals Novel Metabolites and Phospholipid Compositional Rules of Haemophilus influenzae Rd KW20.
Haemophilus influenzae is a gram-negative bacterium of relevant clinical interest. H. influenzae Rd KW20 was the first organism to be sequenced and for which a genome-scale metabolic model (GEM) was developed. However, current H. influenzae GEMs are unable to capture several aspects of metabolome nature related to metabolite pools. To directly and comprehensively characterize the endometabolome of H. influenzae Rd KW20, we performed a multiplatform MS-based metabolomics approach combining LC-MS, GC-MS and CE-MS. We obtained direct evidence of 15-20% of the endometabolome present in current H. influenzae GEMs and showed that polar metabolite pools are interconnected through correlating metabolite islands. Notably, we obtained high-quality evidence of 18 metabolites not previously included in H. influenzae GEMs, including the antimicrobial metabolite cyclo(Leu-Pro). Additionally, we comprehensively characterized and evaluated the quantitative composition of the phospholipidome of H. influenzae, revealing that the fatty acyl chain composition is largely independent of the lipid class, as well as that the probability distribution of phospholipids is mostly related to the conditional probability distribution of individual acyl chains. This finding enabled us to provide a rationale for the observed phospholipid profiles and estimate the abundance of low-level species, permitting the expansion of the phospholipidome characterization through predictive probabilistic modelling.


KCl cotransport mediates abnormal sulfhydryl-dependent volume regulation in sickle reticulocytes.
KCl cotransport (KCC) activation by cell swelling and pH was compared in sickle (SS) and normal (AA) red blood cells (RBCs). KCC fluxes had the same relationship to mean corpuscular hemoglobin concentration (MCHC) in SS and AA RBCs when normalized to the maximal volume-stimulated (VS(max)) flux (MCHC < 270 g/L [27 g/dL]). Acid-stimulated (pH 6.9) KCC flux in SS RBCs was 60% to 70% of VS(max) KCC versus 20% in AA RBCs. Density gradients were used to track changes in reticulocyte MCHC during KCC-mediated regulatory volume decrease (RVD). Swelling to MCHC of 260 g/L (26 g/dL) produced Cl-dependent RVD that resulted in higher MCHC in SS than AA reticulocytes. In acid pH, RVD was also greater in SS than AA reticulocytes. Sulfhydryl reduction by dithiothreitol (DTT) lowered VS(max) KCC flux in AA and SS RBCs by one third but did not alter swelling-induced RVD. DTT lowered acid-activated KCC in SS RBCs by 50% and diminished acid-induced RVD in SS reticulocytes. Thus, swelling activation of KCC is normal in SS RBCs but KCC-mediated RVD produces higher MCHC in SS than AA reticulocytes. Acid activation of KCC is exaggerated in SS RBCs and causes dehydration in SS reticulocytes. KCC response to acid stimulation was mitigated by DTT, suggesting that it arises from sulfhydryl oxidation.


Nociceptin levels in the cerebrospinal fluid of chronic pain patients with or without intrathecal administration of morphine.
The neuropeptide nociceptin/orphanin FQ (N/OFQ) is the endogenous ligand for the opioid-like receptor ORL-1 and is thought to be involved in pain transmission and modulation. Human studies have not yet defined its role in pain patients. The aims of this study were 1) to verify the presence of N/OFQ in the cerebrospinal fluid (CSF) of human controls and patients with chronic noncancer pain, including those treated with intrathecally administered morphine, and 2) to determine whether pain or treatment with long-term intrathecal morphine influences its levels. The CSF of 27 patients (nine controls and 18 with chronic noncancer pain, of whom 12 were treated chronically with intrathecally administered morphine and six were opioid naïve) was analyzed, blindly, with radioimmunoassay methods. N/OFQ was detected in all patients. Mean CSF concentrations were lowest in the morphine-treated group and highest in the untreated chronic pain patients (12.06+/-1.19 and 57.41+/-10.06 fmol/ml, respectively), and the difference between the morphine-treated group and controls was statistically significant (44.72+/-13.56 fmol/ml, P<0.05). The presence of N/OFQ peptide in human CSF may correlate with biological activities that are influenced by different pain states and long-term intrathecal-morphine treatment. Further studies should verify whether the determination of this peptide CSF level may provide information on opioid treatment efficacy and on the presence of opioid tolerance.


Peak C-reactive protein concentration correlates with left ventricular thrombus formation diagnosed by contrast echocardiographic left ventricular opacification in patients with a first anterior acute myocardial infarction.
Wall motion abnormality in the apical legion of the left ventricle (LV) with stagnant flow alone is not sufficient to identify patients at high risk for LV thrombus formation among those with first anterior acute myocardial infarction (AMI). The aim of this study was to identify the determinants of LV thrombus formation using contrast echocardiography. In 75 patients with first anterior AMI, standard and contrast echocardiography was performed to detect LV thrombus. Although LV thrombus was found in 10 patients (13%) using standard echocardiography, it was found in 15 patients (20%) using contrast echocardiography. Apical stagnant flow was observed in 14 patients (93%) with LV thrombus. In addition, patients with LV thrombus had a higher peak C-reactive protein (CRP) concentration (18.2+/-4.3 vs 7.9+/-5.5 mg/dl, p<0.0001). In multivariate analysis, only peak CRP concentration was identified as an independent predictor of LV thrombus (p=0.02, odds ratio: 1.400, confidence interval: 1.040-1.884). The receiver-operating characteristics (ROC) analysis revealed the best cutoff value of a peak CRP concentration >10.7 mg/dl to identify patients with LV thrombus (sensivity 0.93, specificity 0.75, area under ROC curve 0.91). The peak CRP concentration is a useful marker of patients with first anterior AMI who are at high risk for LV thrombus.


A normative study of distortion-product otoacoustic emissions in 6-year-old schoolchildren.
Evoked otoacoustic emissions have demonstrated potential for application in the community-based hearing screening of paediatric populations. Distortion-product otoacoustic emissions (DPOAEs), as opposed to transient evoked otoacoustic emissions (TEOAEs), have not been extensively researched in this regard. The current study aimed to describe the range of DPOAE values obtained in a large cohort (1576 ears) of 6-year-old children in school settings and to examine possible ear asymmetry, gender and history of ear infection effects on the data. Results indicated a variety of significant effects, particularly in the high frequencies, for DPOAE signal-to-noise ratio. The measurement parameter, DPOAE amplitude (DP-amp), was found to display potentially less clinical applicability due to large standard deviation values. Use of descriptive normative data, as derived in the present investigation, may contribute toward future improvements in the hearing screening of 6-year-old schoolchildren.


Effects of an injectable platelet-rich fibrin on osteoblast behavior and bone tissue formation in comparison to platelet-rich plasma.
Platelet-rich plasma (PRP) has been utilized for many years as a regenerative agent capable of inducing vascularization of various tissues using blood-derived growth factors. Despite this, drawbacks mostly related to the additional use of anti-coagulants found in PRP have been shown to inhibit the wound healing process. For these reasons, a novel platelet concentrate has recently been developed with no additives by utilizing lower centrifugation speeds. The purpose of this study was therefore to investigate osteoblast behavior of this novel therapy (injectable-platelet-rich fibrin; i-PRF, 100% natural with no additives) when compared to traditional PRP. Human primary osteoblasts were cultured with either i-PRF or PRP and compared to control tissue culture plastic. A live/dead assay, migration assay as well as a cell adhesion/proliferation assay were investigated. Furthermore, osteoblast differentiation was assessed by alkaline phosphatase (ALP), alizarin red and osteocalcin staining, as well as real-time PCR for genes encoding Runx2, ALP, collagen1 and osteocalcin. The results showed that all cells had high survival rates throughout the entire study period irrespective of culture-conditions. While PRP induced a significant 2-fold increase in osteoblast migration, i-PRF demonstrated a 3-fold increase in migration when compared to control tissue-culture plastic and PRP. While no differences were observed for cell attachment, i-PRF induced a significantly higher proliferation rate at three and five days when compared to PRP. Furthermore, i-PRF induced significantly greater ALP staining at 7 days and alizarin red staining at 14 days. A significant increase in mRNA levels of ALP, Runx2 and osteocalcin, as well as immunofluorescent staining of osteocalcin was also observed in the i-PRF group when compared to PRP. In conclusion, the results from the present study favored the use of the naturally-formulated i-PRF when compared to traditional PRP with anti-coagulants. Further investigation into the direct role of fibrin and leukocytes contained within i-PRF are therefore warranted to better elucidate their positive role in i-PRF on tissue wound healing.


Molecular diversity and evolution of cystine knot toxins of the tarantula Chilobrachys jingzhao.
Cystine knot toxins (CKTs) in spider venoms represent a rich source of novel ligands for varied ion channels. Here, we identified 95 novel putative CKT precursors by analyzing expressed sequence tags of the tarantula Chilobrachys jingzhao venom gland. Phylogenetics analyses revealed one orphan family and six families with sequence similarity to known toxins. To further investigate the relationships of their structures, functions and evolution, we assayed 10 representative toxins for their effect on ion channels, and performed structure model comparisons, evolution analysis and toxin distribution analysis. This study revealed two major types of CKTs: pore-blocking toxins and gating modifier toxins. A few blockers were observed with relatively high abundance and wide distribution, which may be a category of original toxins that block channels conserved in various preys with relatively high specificity. The gating modifier families contain advanced toxins, usually have many members and interact with diverse regulatory components of channels.


Measurement of lip posture and interaction between lip posture and resting face height.
A method for measurement of lip incompetence is described. Electromyographic techniques were used to obtain relaxation of the muscles of the lip and of a jaw elevator muscle. Standardized photographs were taken of the subject's profile, from which lip separation and face height were measured. Variation was found in successive measurements of lip posture, some of which appeared to depend upon mandibular posture. With the teeth in occlusion, lip separation was reduced. Active maintenance of lip contact by the subject was often associated with a reduction in lower face height, which may have been a direct consequence of the lip muscle activity, or of jaw elevator activity facilitating the lip closure.


Increased monocyte chemoattractant protein 1 (MCP-1/CCL-2) serum level in acute myeloid leukemia.
Acute myeloid leukaemia (AML) is an aggressive malignancy with accumulation of blasts in bone marrow. Myeloblasts can entry into peripheral blood stream and secondary localize in extramedullary sites. The regulation of this process has not been clearly explained so far, but interactions between some chemokines and their specific receptors could be one of the mechanisms responsible for such kind of migration. Monocyte chemoattractant protein 1 (MCP-1/CCL2) is the chemokine which could be involved in this process. The aim of the study was to evaluate plasma level of CCL2 in patients with AML. Plasma samples from 65 adult patients with AML taken before chemotherapy and in complete remission were measured by enzyme linked immunoassay to evaluate CCL2 levels. Control group consisted of 15 healthy subjects. In AML patients mean baseline CCL2 level (+/- SEM standard error of measurement) was significantly higher than in normal control: 365,26 +/- 5,62 pg/ml vs 265,56 +/- 5,48 pg/ml respectively (p<0.01). We demonstrate increased mean CCL2 plasma level in untreated patients with AML. Significantly lower plasma level of CCL2 was observed in patients with M4 and M5 AML subtypes according to FAB classification. In AML group chemotherapy did not reduce CCL2 plasma level.


[Carcinoid tumor, a late diagnosis].
Carcinoid tumor is often a late diagnosis due to the unspecificity of symptoms leading the radiologist rely on different investigation procedures. We present a case illustrating the contribution of US by demonstrating the suggestive combination of radiating mesenteric densities with a mesenteric mass.


[Retrospective analysis of outcomes of selectively or spontaneously reduced multiple pregnancies out of 6 917 in vitro fertilization-embryo transfer pregnancy cycles].
Objective: To analyze the effects of fetal reduction in early pregnancy on obstetric and neonatal outcomes of spontaneously or selectively reduced multiple pregnancies produced by in vitro fertilization-embryo transfer (IVF-ET). Methods: Retrospective study of 6 917 clinical pregnancies from IVF-ET cycles, including 754 multiple pregnancies divided into two groups according to the remaining fetus number: reduced singleton group (n=599) and reduced twin group (n=155); and maternal and neonatal outcomes of two groups were compared to primary singleton group (n=3 589) and primary twin group (n=2 574). Results: The rate of pregnancy complication [9.85%(59/599) versus 6.21%(223/3 589)], preterm birth [19.37%(116/599) versus 10.73%(385/3 589)], low birth weight [9.71%(56/577) versus 4.57% (152/3 324)], perinatal death [0.69%(4/577) versus 0.12%(4/3 324)] and malformation [2.95%(17/577) versus 1.02%(34/3 324)] in reduced singleton group were significantly higher than those in primary singleton group (all P<0.01). There were no significant differences between reduced twin group and primary twin group (all P>0.05). In reduced singleton group, birth defect rate was 2.95%, which was higher than those of the other three groups (P<0.05), in this group spontaneous pregnancy reduction accounted for 89.3% (535/599). Conclusions: (1) The rate of pregnancy complication, preterm birth, low birth weight, perinatal death and malformation in reduced singleton group are still higher than primary singletons, suggesting embryo reduction only is a compensated method in multiple pregnancies. Limiting the number of embryos transferred is the essential solution. (2) The rate of birth defect in spontaneous pregnancy reduction group is higher, so prenatal examination should be reinforced in this group.


Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni.
Campylobacter jejuni is a leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, its mechanisms of pathogenesis are poorly understood. Peptidoglycan (PG) is important for helical shape, colonization, and host-pathogen interactions in C. jejuni Therefore, changes in PG greatly impact the physiology of this organism. O-acetylation of peptidoglycan (OAP) is a bacterial phenomenon proposed to be important for proper cell growth, characterized by acetylation of the C6 hydroxyl group of N-acetylmuramic acid in the PG glycan backbone. The OAP gene cluster consists of a PG O-acetyltransferase A (patA) for translocation of acetate into the periplasm, a PG O-acetyltransferase B (patB) for O-acetylation, and an O-acetylpeptidoglycan esterase (ape1) for de-O-acetylation. In this study, reduced OAP in ΔpatA and ΔpatB had minimal impact on C. jejuni growth and fitness under the conditions tested. However, accumulation of OAP in Δape1 resulted in marked differences in PG biochemistry, including O-acetylation, anhydromuropeptide levels, and changes not expected to result directly from Ape1 activity. This suggests that OAP may be a form of substrate level regulation in PG biosynthesis. Ape1 acetylesterase activity was confirmed in vitro using p-nitrophenyl acetate and O-acetylated PG as substrates. In addition, Δape1 exhibited defects in pathogenesis-associated phenotypes, including cell shape, motility, biofilm formation, cell surface hydrophobicity, and sodium deoxycholate sensitivity. Δape1 was also impaired for chick colonization and adhesion, invasion, intracellular survival, and induction of IL-8 production in INT407 cells in vitro The importance of Ape1 in C. jejuni biology makes it a good candidate as an antimicrobial target.


Production of biodiesel using immobilized lipase--a critical review.
Increase in volume of biodiesel production in the world scenario proves that biodiesel is accepted as an alternative to conventional fuel. Production of biodiesel using alkaline catalyst has been commercially implemented due to its high conversion and low production time. For the product and process development of biodiesel, enzymatic transesterification has been suggested to produce a high purity product with an economic, environment friendly process at mild reaction conditions. The enzyme cost being the main hurdle can be overcome by immobilization. Immobilized enzyme, which has been successfully used in various fields over the soluble counterpart, could be employed in biodiesel production with the aim of reducing the production cost by reusing the enzyme. This review attempts to provide an updated compilation of the studies reported on biodiesel production by using lipase immobilized through various techniques and the parameters, which affect their functionality.


Complete Genome Sequence of Lactobacillus helveticus JCM 1004, an Aminopeptidase-Producing Lactic Acid Bacterium.
We report the complete genome sequence of Lactobacillus helveticus JCM 1004, an aminopeptidase-producing lactic acid bacterium. The genome consists of a circular chromosome which comprises 2,261,280 bp, with a G+C content of 37.56%. The genome was predicted to harbor 13 rRNA genes, 64 tRNA genes, and 2,462 protein-coding sequences.


Pseudohypoparathyroidism type 1a with congenital hypothyroidism.
Pseudohypoparathyroidism type la (PHP-1a) is an uncommon disorder that results from an inactivating mutation in the GNAS gene. It can present with resistance to several hormones, in addition to parathyroid hormone (PTH). Patients may have the classic Albright's hereditary osteodystrophy (AHO) phenotype and can develop resistance to thyroid stimulating hormone (TSH), gonadotropins, growth hormone releasing hormone (GHRH), and other hormones that rely on the Gsalpha protein to regulate signal transmission at their receptors. We report two siblings with PHP-1a and congenital hypothyroidism. The patients were found to have a heterozygous mutation at nucleotide 305 in exon 4 (c305C-->A) of the GNAS gene, which has not been previously linked to congenital hypothyroidism.


Alkyne-Tagged Analogue of Jaspine B: New Tool for Identifying Jaspine B Mode of Action.
The first biologically relevant clickable probe related to the antitumor marine lipid jaspine B is reported. The concise synthetic route to both enantiomers relied on the supercritical fluid chromatography (SFC) enantiomeric resolution of racemic materials. The eutomeric dextrogyre derivative represents the first jaspine B analogue with enhanced cytotoxicity with IC50 down to 30 nm. These enantiomeric probes revealed a chiralitydependent cytoplasmic imaging of U2OS cancer cells by in situ click labeling.


Novel fused pyrimidine and isoquinoline derivatives as potent HIV-1 NNRTIs: a patent evaluation of WO2016105532A1, WO2016105534A1 and WO2016105564A1.
In the three patent applications, the impact of changing the pyrimidine core of the rilpivirine (RPV) to a variety of alternative fused cores was explored, culminating in the identification of a series of conformationally restricted compounds with comparable potencies against WT and mutant HIV-1 strains with those of efavirenz (EFV) and RPV, and higher security in the Human Ether-a-go-go-Related Gene (hERG) assay. Areas covered: The present review provides a fused pyrimidine and isoquinoline derivatives as potent HIV-1 NNRTIs, and highlights the conformational restriction strategies in the development of NNRTIs. Expert opinion: The molecular docking analysis of the newly synthesized compounds maintain the classical horseshoe conformation and shares similar binding mode with RPV. The conformational restriction strategies have greatly accelerated the optimization of the DAPY NNRTIs and contribute to finding new chemical entities (NCEs) with favorable druggability.


Intracellular substrates for endogenous metabolism during long-term starvation of rod and spherical cells of Arthrobacter crystallopoietes.
Cells of Arthrobacter crystallopoietes, harvested during growth as spheres and as rods, were starved by shaking at 30 C in phosphate buffer for 30 days, during which time they maintained 100% viability. Changes in cellular components and the activity of specific enzyme pathways were monitored. A glycogen-like polysaccharide comprised 40% of the dry weight of growing spherical cells and 10% of the dry weight of rod cells. This material was utilized at approximately the same rate, on a percentage basis, during starvation of both cell forms. The rods degraded intracellular protein at approximately twice the rate of the spheres. At the end of 30 days, the rods had degraded 40% and the spheres 20% of their initial content of protein. Ribonucleic acid (RNA) was degraded significantly more rapidly in the rods. After 30 days starvation, 85 and 32% of the initial RNA of rods and spheres, respectively, had been depleted. Magnesium ion followed this same general pattern; the rods lost 65% and the spheres 45% of their initial content during 28 days of starvation. Deoxyribonucleic acid increased by 20% during the first few hours of starvation of both cell forms and then remained constant. The ability of glucose-, succinate-, and 2-hydroxypyridine (2-HP)-grown cells to oxidize glucose remained constant during 14 days of starvation. The ability of succinate-grown cells to oxidize succinate decreased rapidly during the first few hours of starvation to a rate which remained constant for 14 days. Cells adapted to growth on 2-HP completely lost their ability to oxidize this substrate after 3 days starvation.


NAD (P)H Quinone Dehydrogenase 1-Targeting Triptolide Analogue Causes Tumor Regression and Sensitizes Cisplatin-Resistant Lung Cancer to Chemotherapy.
Cisplatin (DDP) is a first-line chemotherapeutic drug against lung cancer. Nonetheless, the effectiveness of this drug is hampered by drug resistance. Overcoming drug resistance is crucial for improving the outcomes of lung cancer treatment. Here, we reported the effect of CX-23, an activated triptolide analogue that targets NAD (P)H quinone dehydrogenase 1 (NQO1), on DDP-resistant lung cancer and sensitizes DDP-resistant lung cancer to chemotherapy. Our findings unveiled the antiproliferative activity of CX-23 against both A549- and DDP-resistant A549 (A549/DDP) cells while enhancing the chemosensitivity of these cells to DDP. Notably, CX-23 demonstrated no toxicity toward normal lung cells. Further investigations revealed that CX-23 exerts its effects by blocking AKT phosphorylation, leading to reduced expression of Mcl-1 and Bcl-2, and upregulating cleaved-caspase-3 levels, ultimately inducing apoptosis in cancer cells. CX-23 can be rapidly transformed in both A549 and A549/DDP cell lysates while remaining stable in mouse plasma and normal lung tissues. Pharmacokinetic analysis showed that CX-23 can distribute to lung tissues. Moreover, in vivo studies showed that CX-23 can prevent DDP-resistant lung cancer progression without causing any toxicity in the liver, kidneys, or lungs after 6 weeks of treatment. The combination of CX-23 and DDP not only significantly inhibited tumor progression compared to DDP alone but also attenuated DDP-induced kidney toxicity. These findings suggest that CX-23 alone or in combination with DDP may provide an alternative therapeutic option for DDP-resistant lung cancer.


Effects of the respiratory stimulant almitrine on breathing and FOS expression in the brain of fetal and newborn sheep.
Almitrine is a piperazine derivative known to stimulate breathing in the adult but cause apnea in fetal sheep. In fetal sheep (127-133 d gestation; term = 147 d) we confirmed this finding, but found that almitrine (4 mg/kg, i.v. or intra-arterial) had a biphasic effect, briefly stimulating and then suppressing breathing movements for at least 3 h. In 2- to 3-d-old (n = 4) and 7- to 14-d-old (n = 4) lambs almitrine increased both tidal volume and breath frequency, increased arterial partial pressure of oxygen and pH, and decreased partial pressure of carbon dioxide. The changes of tidal volume, partial pressure of oxygen and partial pressure of carbon dioxide were less in the 2- to 3-d-old compared with the 7- to 14-d-old lambs. The distribution of the nuclear phosphoprotein FOS, a marker of neuronal activation was examined in fetal and newborn brains. FOS protein was increased in cardiorespiratory areas of the medulla and pons, in the periaqueductal region of the midbrain, and in the supraoptic and paraventricular regions of the hypothalamus. In the pons, FOS protein was increased in the medial parabrachial and subcoeruleus nuclei in the fetuses but not in the 2- to 3- or 7- to 14-d-old lambs. These observations are similar to those reported for hypoxia, and consistent with the hypothesis that both almitrine and hypoxia inhibit fetal breathing movements by an action on a select group of pontine neurons. Whether these neurons respond directly to these stimuli or receive input from the other centers is yet to be elucidated. The mechanisms that change the almitrine (and hypoxia) response from inhibition to excitation at birth have not been identified, but may be important in preventing apnea in the newborn.


[Animal Welfare Service of Lower Saxony--first report of experiences].
The Animal Welfare Service of Lower Saxony-part of the state veterinary services within the regional government of Weser-Ems-started its work in February 1995 at Oldenburg. The experiences during the first 18 months of activity are discussed. The main duties of the Service consist of: Advising the local district veterinary authorities concerning "problem" holdings including common control visits on occasion. Advising the offices of the court on matters concerning animal protection. Advising government offices and legislative bodies on the development and improvement of animal welfare legislation. Working on special problems of animal welfare. In particular the Service aided by various working groups is currently establishing welfare recommendations for the special fields of turkey fattening and all year grazing of cattle and sheep.


Emotional Experience and Psychological Intervention of Depression Patients Based on SOM.
Depression is a severe mental illness with an unknown pathogenesis. Clinical diagnosis is based primarily on symptoms and does not include objective biological markers. Finding objective markers for diagnosis and treatment from imaging, on the contrary, is becoming increasingly important. The SOM (self-organizing feature mapping) model was used to identify the depression tendency of users in order to investigate the emotional experience and psychological intervention of patients with depression. On this foundation, the concept of depression index is developed further, and the relationship between depression index and the severity of depression in patients is thoroughly investigated. The system can accurately and quickly identify the depression state by applying it directly to the original EEG signals, without any preprocessing or feature extraction. When combined with traditional classifiers, the analysis and comparison results show that SOM can not only effectively select features but also improve the accuracy of depression classification. This research proposes a new research direction for deep learning in the context of large-scale big data analysis.


Esthetic improvement in the patient with one missing maxillary central incisor restored with porcelain laminate veneers.
This article describes esthetic improvement in a patient with a missing maxillary left central incisor. Space analysis of the anterior dentition showed that minor tooth rearrangement was needed. Optimal space distribution for restorations was attained by orthodontic treatment. Through transforming tooth shape with porcelain laminate veneers, the maxillary left lateral incisor was transformed into central incisor and the maxillary left canine into a lateral incisor. The maxillary right central incisor was also restored for esthetic improvement. In a case of changing a tooth shape with porcelain laminate veneers, pre-treatment evaluation, space analysis and diagnostic wax-up are important factors.


The connectivity map links iron regulatory protein-1-mediated inhibition of hypoxia-inducible factor-2a translation to the anti-inflammatory 15-deoxy-delta12,14-prostaglandin J2.
Hypoxia-inducible factors 1 and 2 (HIF1 and HIF2) are heterodimeric transcription factors consisting of alpha regulatory subunits and a constitutively expressed beta subunit. The expression of alpha regulatory subunits is promoted by hypoxia, cancer-associated mutations, and inflammatory cytokines. Thus, HIF1 and HIF2 provide a molecular link between cancer and inflammation. We have recently identified novel small molecules that selectively inhibit translation of the HIF2a message and thereby powerfully inhibit the expression of HIF2a target genes. We report here that Connectivity Map analysis links three of these compounds to the anti-inflammatory cytokine 15-deoxy-Delta(12,14)-prostaglandin J(2) (PGJ(2)). As with our identified compounds, PGJ(2) inhibits translation of the HIF2a message in a mammalian target of rapamycin-independent manner by promoting the binding of iron regulatory protein-1 (IRP1) to a noncanonical iron responsive element (IRE) embedded within the 5'-untranslated region of the HIF2a message. The IRE is necessary and sufficient for mediating the effect. Mutation of the IRE sequence, or downregulation of IRP1 expression, blocks the effect of PGJ(2) on HIF2a translation. This is the first report of an endogenous natural molecule regulating HIF2a translation, and it suggests that part of the anti-inflammatory and putative antineoplastic effects of PGJ(2) may be mediated through inhibition of HIF2a within tumor epithelial cells themselves and/or mesenchymal cells of the tumor microenvironment.


Gender and motor competence affects perceived likelihood and importance of physical activity outcomes among 14 year olds.
Perceptions of the effects of physical activity could facilitate or deter future participation. This study explored the differences between gender and motor competence at 14 years of age in the perceptions of likelihood and importance of physical activity outcomes. The sample comprised 1582 14-year-old adolescents (769 girls) from the Western Australian Pregnancy Cohort (Raine) Study. Four motor competence groups were formed from a standardized Neuromuscular Developmental Index score (McCarron 1997). Perceptions of the likelihood and the importance of 15 physical activity outcomes were measured by a questionnaire developed for the NSW Schools Fitness and Physical Activity Survey (Booth et al. 1997). Gender (two) × motor competence (four) analyses of variance and Tukey post hoc were conducted on outcome scores (P < 0.02) using SPSS version 17. Gender differences were found in the perceived likelihood and importance of physical activity outcomes within competition, social friendships and injury domains. Motor competence was significant in the perceived likelihood of physical health (P < 0.001), psychosocial (P < 0.009) and competition (P < 0.002) outcomes, with lower perceptions by the least competent groups. Significantly lower importance was perceived for academic outcomes for 14 year olds categorized with low compared with high motor competence (P < 0.005). Regardless of motor competence and gender, the same health and fun outcomes were ranked the highest in likelihood and the highest in importance. Although level of motor competence at 14 years affected the perceived likelihood of health, social and fun outcomes from future participation in physical activity, adolescents highly valued these outcomes, whereas gender affected competition and winning, outcomes that were less valued. Physical activity that promotes these key and valued outcomes may encourage young people's ongoing involvement in physical activity, especially for those at risk of low participation.


Adipose tissue distribution and female carcinomas. A 12-year follow-up of participants in the population study of women in Gothenburg, Sweden.
A longitudinal population study of 1462 women, aged 38-60 years, was carried out in Gothenburg, Sweden, in 1968-69. In univariate analysis anthropometric variables indicating centrally localized adipose tissue (waist circumference, the ratio of waist to hip circumference and the subscapular skinfold) showed significant age-standardized positive associations with the occurrence (prevalence + incidence data) of endometrial carcinoma. Incidence data suggested that measurements of centrally localized adipose tissue might be of predictive value for this malignancy as well as for ovarian carcinoma. In contrast, measurements of generalized obesity (body weight or body mass index) or peripherally localized adipose tissue (triceps skinfold) showed no associations to these malignancies. No relationship was observed between the anthropometric variables studied and breast carcinoma. The association observed between endometrial and ovarian carcinomas with central adipose tissue did, however, not remain in multivariate analysis when generalized obesity was taken into account. Centrally localized adipose tissue is known to be associated with endocrine abberations including irregular ovulation and menstruation, re-emphasizing the importance of endocrine factors for the pathogenesis of endometrial and ovarian carcinomas. No positive association was found between development of the carcinomas and initial measurements of blood glucose, serum lipids or blood pressure, found to be elevated in cross-sectional studies. An increase in these variables therefore probably are parallel phenomena rather than predictors. The women with endometrial or breast carcinomas smoked more than the remaining women. Although the number of end-points observed was limited these results suggest that measurements of adipose tissue distribution might be a valuable addition to the predictors of endometrial and ovarian carcinomas.(ABSTRACT TRUNCATED AT 250 WORDS)


Modulation of the Binding Affinity of Polyzwitterion-Conjugated Protein by Ion-Specific Effects in Crowded Environments.
Macromolecular crowding could influence the binding affinity of the polyzwitterion-conjugated proteins. Herein, the hydrolysis of N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide by the poly(carboxybetaine) conjugated α-chymotrypsin (PCT) was employed as a model system to investigate the modulation of the binding affinity of the polyzwitterion-conjugated proteins by the ion-specific effects in the crowded environments. In comparison with the bare α-chymotrypsin (BCT), the binding affinity of the PCT to the peptide is stronger in the dilute solutions but becomes weaker in the crowded environments. Our study demonstrates that the kosmotropic Ac- anion is incapable of achieving a stronger enzymatic binding affinity of the PCT than the BCT in the highly crowded environments. By contrast, the binding affinity of the PCT can be enhanced to be stronger than that of the BCT by the chaotropic SCN- anion in the crowded environments.


Dual-channel recording based on the null reconstruction effect of orthogonal linear polarization holography.
We report on dual-channel recording within polarization holography written by orthogonal linear polarization waves. The null reconstruction effect (NRE) of linear polarization holography was experimentally achieved at a large cross-angle of π/2 inside the polarization-sensitive media. Based on the NRE, two polarization encoded holograms were recorded in a dual-channel recording system with negligible inter-channel crosstalk. The two polarization multiplexed holograms could then be sequentially or simultaneously readout by shifting the polarization state of reference wave with the best signal-to-noise of 18:1 obtained within the experiment.


Transcription termination factor rho activity is altered in Escherichia coli with suA gene mutations.
Rho factor has been purified from a strain of E. coli containing the Su78 mutation in the suA gene and assayed in another strain with an amber mutation in the suA gene. The rho from the Su78 mutant strain is present in normal amounts but has altered termination function; it does not terminate transcription at some sites that are recognized effectively by the rho factor from the isogenic wild-type strain. Rho in cells with an amber mutation in the suA gene has been assayed by its RNA-dependent ATPase activity. Extracts of cells of this strain have only 9% as much of this rho activity as extracts of cells of the isogenic wild-type strain. These results suggest that rho is the product of the suA gene. Since mutations in the suA gene are known to decrease polar effects of mutations in other genes, it is also suggested that rho factor is at least partially responsible for polar effects.


Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1.
The control of human immunodeficiency virus type 1 (HIV-1) associated with particular HLA class I alleles suggests that some CD8(+) T-cell responses may be more effective than others at containing HIV-1. Unfortunately, substantial diversities in the breadth, magnitude, and function of these responses have impaired our ability to identify responses most critical to this control. It has been proposed that CD8 responses targeting conserved regions of the virus may be particularly effective, since the development of cytotoxic T-lymphocyte (CTL) escape mutations in these regions may significantly impair viral replication. To address this hypothesis at the population level, we derived near-full-length viral genomes from 98 chronically infected individuals and identified a total of 76 HLA class I-associated mutations across the genome, reflective of CD8 responses capable of selecting for sequence evolution. The majority of HLA-associated mutations were found in p24 Gag, Pol, and Nef. Reversion of HLA-associated mutations in the absence of the selecting HLA allele was also commonly observed, suggesting an impact of most CTL escape mutations on viral replication. Although no correlations were observed between the number or location of HLA-associated mutations and protective HLA alleles, limiting the analysis to mutations selected by acute-phase immunodominant responses revealed a strong positive correlation between mutations at conserved residues and protective HLA alleles. These data suggest that control of HIV-1 may be associated with acute-phase CD8 responses capable of selecting for viral escape mutations in highly conserved regions of the virus, supporting the inclusion of these regions in the design of an effective vaccine.


DDAVP in type IIa von Willebrand's disease.
1-D-Amino(8-D-arginine)-vasopressin (DDAVP) infusion in three patients with type IIa von Willebrand's disease (vWD) resulted in a normalization of the factor VIII coagulant, factor VIII-related antigen, and von Willebrand factor (vWF) (ristocetin cofactor) activities and the bleeding time. The normalization of these hemostatic parameters persisted for four hours. Over the same time period there was a marked increase in the quantity of the vWF multimers when blood was collected in the presence of protease inhibitors. The vWF multimers present were even larger than the normal. When blood was collected in the absence of protease inhibitors, a smaller increase in the plasma vWF multimers was observed and fewer of the intermediate and larger vWF multimers were seen; multimers larger than those present in normal plasma were not visualized. The platelet vWF multimers and activities did not change with or without inhibitors. These studies suggest that there is a subgroup of patients with type IIa vWD who respond to DDAVP with complete normalization of their hemostatic abnormalities and whose vWF is sensitive to proteolysis.


Yield of advanced adenoma and cancer based on polyp size detected at screening flexible sigmoidoscopy.
Observational screening of the colon with subsequent referral for colonoscopy raises questions about the threshold of polyp size that necessitates referral. To examine the yield at colonoscopy when a given size lesion is observed, we assessed the yield of advanced adenoma and cancer at colonoscopy based on the size of the abnormality detected at flexible sigmoidoscopy (FSG). We used data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a randomized, controlled, community-based study of FSG. Subsequent colonoscopy was performed on 10,850 subjects (60.4% male; mean age, 62.9 years) with a polyp visualized on screening FSG. For women with a polyp 0.5-0.9 cm on FSG (n = 1426), the yield in the distal colon on colonoscopy was 0.6% for cancer (number needed to screen [NNS] = 166) and 14.5% for advanced adenoma (NNS = 7). In men (n = 2183), the yield was 0.7% (NNS = 142) for cancer and 15.9% (NNS = 6) for advanced adenoma. Among persons with polyps 0.5-0.9 cm identified on FSG, 5.5% (198/3609) had distal advanced adenomas that measured <1.0 cm but had villous histology or high-grade dysplasia, and 9.9% (357/3609) had adenomas > or =1 cm. The yield for a distal advanced adenomatous lesion when a polyp 0.5-0.9 cm is observed at FSG is substantial and is due to the presence of advanced histology in polyps <1 cm and to detection of polyps that measure > or =1.0 cm on colonoscopy. Establishing thresholds for observation versus evaluation will require careful assessment of the overall yield.


Antioxidative Activity of Onion Peel Extract in Obese Women: A Randomized, Double-blind, Placebo Controlled Study.
Quercetin, found abundantly in onion peel, has been known to have anticholesterol, antithrombotic and insulin-sensitizing properties. Here, we investigated the effect of quercetin-rich onion peel extract (OPE) on reactive oxygen species (ROS) production and antioxidative defense in obese woman. This study was randomized, double-blind, placebo controlled study. Thirty-seven healthy obese participants were randomly assigned that eighteen subjects received red soft capsuled OPE (100 mg/d, 50 mg bis in die), while the other nineteen subjects received same capsuled placebo for 12 weeks. ROS production and superoxide dismutase (SOD) activity in plasma were determined by using ROS and SOD assay kits, respectively. Baseline characteristics of anthropometric indicators and blood metabolic profiles were not significantly different between the two groups. Compared with baseline values, OPE consumption significantly reduced waist and hip circumference. Plasma ROS level and SOD activity were decreased in both placebo and OPE groups compared with baseline values. However, plasma ROS level in OPE group was significantly lower than in placebo group while plasma SOD activity in OPE group was significantly higher than in placebo group after 12 weeks of consumption. These findings indicate that OPE consumption may exert antioxidative effect by preventing the decrease of SOD activity as well as the production of ROS in obese women.


Family Network, Workplace Network, and Their Influence on Condom Use: A Qualitative Study Among Older Female Sex Workers in China.
The objective of this study was to qualitatively explore the components of social networks and their influence on condom use among female sex workers (FSWs) aged 35 years and older in China. In-depth interviews with 63 older FSWs and 6 focus group interviews with pimps and owners of roadside salons and hotels were conducted in 3 Chinese cities. The mean age of participants was 42.6 years old (SD = 6.9 years) and the mean age of starting sex work was 38.6 years old (SD = 6.6 years). Two types of networks that influenced condom use were identified: family networks (relationship with children and husbands) and workplace networks (relationship with peers, clients, pimps, and owners). Relationships between older FSWs and their children negatively influenced condom use. Low levels of network support and norms regarding condom use were observed in the relationship between older FSWs and their clients, whereas positive social support and norms were prevalent among older FSWs who had frequent contact with peers. Norms for condom use existed among pimps and owners but were counterbalanced by monetary gains. Future human immunodeficiency virus (HIV) interventions for older FSWs should take the different features of social network components into consideration.


The relationships among peak torque, mean power output, mechanomyography, and electromyography in men and women during maximal, eccentric isokinetic muscle actions.
The purpose of the present investigation was to examine the velocity-related patterns of peak torque (PT), mean power output (MP), mechanomyographic (MMG) amplitude, and electromyographic (EMG) amplitude of the vastus lateralis (VL) muscle in men and women during maximal, eccentric isokinetic muscle actions of the leg extensors. Eight women [mean (SD)] [aged 23 (3) years] and seven men [aged 23 (2) years] volunteered for this investigation. Their PT was measured on a calibrated dynamometer at randomly ordered velocities of 30, 90, and 150 degrees x s(-1). A piezoelectric MMG recording sensor was placed between bipolar surface EMG electrodes (Ag-AgCl) over the VL muscle. Their MP was determined using the dynamometer software. The results indicated no sex-related differences (P > 0.05) for the patterns of PT, MP, MMG amplitude, or EMG amplitude across velocity. The normalized values for MP and MMG amplitude increased (P<0.05) from 30 to 150 degrees x s(-1) (30 degrees x s(-1) <90 degrees x s(-1) < 150 degrees x s(-1)), while PT and EMG amplitudes remained unchanged across velocity. The results indicated close associations between the velocity-related patterns of MP and MMG amplitudes as well as PT and EMG amplitudes. Thus, MMG amplitude reflected the velocity-related changes in muscle power output, but not torque production, while EMG amplitude reflected torque production, but not muscle power output. During maximal, eccentric isokinetic muscle actions, EMG and MMG signals provided unique information regarding the electrical and mechanical aspects of muscle strength and power.


Pathophysiology of stroke.
Therapeutic intervention in acute ischemic stroke must be directed at salvaging damaged, but viable, tissue. Ideally, treatment should start in the initial phase when the ischemic tissue still retains a potential for recovery. Furthermore, ischemic stroke may be associated with "chronic threatening ischemia," in which there is ischemic, but viable, tissue with collateral circulation distal to a stenosed or occluded artery. In chronic threatening ischemia, therapeutic manipulation may improve the clinical situation. Since cerebral vasomotor function is impaired or abolished in acute stroke and chronic threatening ischemia, vasodilator therapy tends to "steal" blood away from the lesion. Vasoconstrictors, by decreasing perfusion in healthy parts of the brain, may improve perfusion in ischemic tissue; it has, however, proved difficult to gain clinical benefit from this therapeutic modality. Converting-enzyme inhibitors may have a place in the management of ischemic stroke as they tend to shift cerebral autoregulation toward lower pressures. Calcium antagonists given acutely in stroke may create a steal effect. Despite this, clinical trials indicate that calcium-antagonist treatment may improve the outcome of stroke patients, possibly by an action on the ischemia-threatened brain cells.


5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with microwave.
This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.


Children With Mild Bilateral and Unilateral Hearing Loss: Parents' Reflections on Experiences and Outcomes.
Children with mild bilateral and unilateral hearing loss are now commonly identified early through newborn hearing screening initiatives. There remains considerable uncertainty about how to support parents and about which services to provide for children with mild bilateral and unilateral hearing loss. The goal of this study was to learn about parents' experiences and understand, from their perspectives, the impact of hearing loss in the mild range on the child's functioning. Parents of 20 children in Ontario, Canada, participated in the study. The median age of identification of hearing loss was 4.6 months (interquartile range: 3.6, 10.8). Parents appreciated learning early about hearing loss, but their experiences with the early process were mixed. Parents felt that professionals minimized the importance of milder hearing loss. There was substantial uncertainty about the need for hearing aids and the findings suggest that parents need specific guidance. Parents expressed concerns about the potential impact of hearing loss on their child's development, particularly at later ages.


Indentation of graphene nano-bubbles.
Molecular dynamics simulations are used to investigate the effect of an AFM tip when indenting graphene nano bubbles filled by a noble gas (i.e. He, Ne and Ar) up to the breaking point. The failure points resemble those of viral shells as described by the Föppl-von Kármán (FvK) dimensionless number defined in the context of elasticity theory of thin shells. At room temperature, He gas inside the bubbles is found to be in the liquid state while Ne and Ar atoms are in the solid state although the pressure inside the nano bubble is below the melting pressure of the bulk. The trapped gases are under higher hydrostatic pressure at low temperatures than at room temperature.


Antihypertensive action of angiotensin-I converting enzyme inhibitors in the kidney.
In order to elucidate the antihypertensive action of angiotensin-I converting enzyme inhibitors (CEIs) in the kidney, intrarenal (IR) administration of CEIs was performed in norepinephrine (NE) or angiotensin-II (AII) induced acute hypertension in conscious unrestrained rabbits. IR administration of the two kinds of CEIs, captopril (5 mg/kg) and MK-422 (1 mg/kg), dose which caused no significant effect when injected intravenously, elicited a prompt and marked depressor action in NE but not in AII induced hypertension. In addition, IR infusion of the angiotensin-II analogue, saralasin (2 and 10 micrograms/kg/min) showed no depressor effect in NE induced acute hypertension. These results indicate that the kidney plays an important role in the depressor action of CEIs in NE but not in AII induced hypertension and this effect may not be related to the IR renin-angiotensin system.


The association between arterial stiffness and fluid status in peritoneal dialysis patients.
In this study our aim was to evaluate the relationship between degree of fluid status and arterial stiffness measured by pulse wave velocity (PWV) in peritoneal dialysis (PD) patients. Fluid status was determined by different methods including fluid overload measured by bioimpedance (Body Composition Monitor, BCM), calf normalized resistivity (CNR), plasma N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and extracellular to intracellular water ratio (ECW/ICW). Sixty PD patients were evaluated. They were stratified into normo- and hypervolemic groups according to their fluid overload (FO). CNR was calculated from resistance at 5 kHz using calf bioimpedance spectroscopy. Arterial stiffness was assessed by PWV. Additionally, all patients underwent transthoracic echocardiography and had levels of NT-proBNP measured. PWV was higher in the hypervolemic compared to normovolemic patients (9.99 ± 2.4 m/sec vs 7.48 ± 2.3 m/sec, p < 0.001). Hypervolemic patients had higher NT-proBNP levels (3065 ± 981 pg/mL vs 1095 ± 502 pg/mL, p < 0.001), a higher ratio of ECW/ICW; (0.93 ± 0.11 vs 0.81 ± 0.08, p < 0.001) and lower CNR (13.7 ± 2.4 vs 16.0 ± 3.3 W m(3)/kg(*)10(-2), p = 0.005). NT-pro BNP level, ECW/ICW ratio, relative FO, and left ventricular (LV) mass index were positively and CNR negatively correlated with PWV. Relative FO and CNR independently predicted PWV in multivariate analysis adjusted for age, duration of PD, body mass index and mean arterial pressure. Arterial stiffness is increased in fluid-overloaded PD patients. Our results indicated that fluid status is an independent predictor of PWV.


INSANITY AND CRIMINAL OFFENDERS. SOME COMMENTS ON THE REPORT OF GOVERNOR'S SPECIAL COMMISSIONS ON INSANITY AND CRIMINAL OFFENDERS.
The definition proposed by the Commissions on Insanity and Criminal Offenders for determining criminal responsibility will not resolve the issue between offenders who are considered blameworthy and regarded as criminals and those who are not. No formula is satisfactory for differentiating responsibility and irresponsibility. Determinism, which is the fundamental tenet of all science, is violated by the assumption that an individual can wilfully elect to commit an act which, in fact, is the result of causal antecedents. This concept is in conflict with the basic premise of criminal law that an individual is considered criminally responsible unless it can be proved to the contrary. Since it is unlikely that any proposal to abolish the concept of criminal responsibility would be even considered, it is suggested that no definition be used at all. Laws similar to those for the disposition of the mentally ill could be enacted, with emphasis not on the concept of criminal responsibility and moral blameworthiness but on the offender's dangerousness to others, the disposition then being planned to fit the offender rather than the offense.


Cost-effectiveness analysis of PD-1 inhibitors combined with chemotherapy as first-line therapy for advanced esophageal squamous-cell carcinoma in China.
Objective: This study was aimed to investigate the cost-effectiveness of all available programmed death 1 (PD-1) inhibitors combined with chemotherapy in the first-line treatment of advanced esophageal squamous-cell carcinoma (ESCC) from the Chinese healthcare system perspective. Methods: A partitioned survival model with a 3-week cycle and a 10-year time horizon was constructed based on a network meta-analysis. The survival data and utility values were derived from clinical trials, and the direct medical costs were collected from public drug bidding database and published literature. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with mono-chemotherapy, toripalimab, sintilimab and camrelizumab plus chemotherapy were cost-effective treatment regimens, while serplulimab, pembrolizumab and nivolumab plus chemotherapy were not cost-effective options. Toripalimab plus chemotherapy provided the highest QALYs of 0.95 with the lower cost of $8,110.53 compared to other competing alternatives. The robustness of the base-case results was confirmed by scenario and one-way sensitivity analysis. At a willingness-to-pay threshold of three times per capita gross domestic product ($38,351.20) in 2021, the probability of toripalimab plus chemotherapy being the optimal option was 74.25% compared with other six competing alternatives. Conclusion: Toripalimab plus chemotherapy represented the most cost-effective option as the first-line therapy for advanced ESCC patients in China.


Creating consensus on coverage choices.
The framework for reaching near-universal coverage outlined in this paper combines tax credits for private insurance and public program expansions. It illustrates how a series of incremental steps could be phased in to achieve near-universal coverage. Hallmarks include creation of a Congressional Health Plan; use of the income tax system to provide tax credits and enroll uninsured people; creation of a state Family Health Insurance Program open to everyone below 150 percent of poverty; and creation of a Medicare Part E, open to the disabled and uninsured older adults. The paper provides coverage and cost estimates and identifies potential sources of revenue to finance coverage.


Effect of Placebo Conditions on Polysomnographic Parameters in Primary Insomnia: A Meta-Analysis.
Little is known about the role of placebo response in the pharmacotherapy of primary insomnia, especially about the effect of placebo intake on objectively assessed outcome variables. Our aim was therefore to conduct an effect-size analysis of placebo conditions in randomized controlled drug trials addressing primary insomnia also including polysomnography. We conducted a comprehensive literature search using PubMed, PsycINFO, PSYNDEX, PQDT OPEN, OpenGREY, ISI Web of Knowledge, Cochrane Clinical Trials, and the World Health Organization International Clinical Trials Registry Platform. The meta-analysis used a random effects model and was based on 32 studies reporting 82 treatment conditions covering a total of 3,969 participants. Special emphasis was given to the comparison of objective and subjective outcomes and the proportion of the placebo response to the drug response. Effect sizes estimates (Hedges g) suggest that there is a small to moderate yet significant and robust placebo response reducing the symptoms of insomnia in terms of sleep onset latency (-0.35), total sleep time (0.42), wake after sleep onset (-0.29), sleep efficiency (0.31), subjective sleep onset latency (-0.29), subjective total sleep time (0.43), subjective wake after sleep onset (-0.32), subjective sleep efficiency (0.25) and sleep quality (0.31). Thus, the placebo response was also evident in objective, physiological (polysomnographic) variables. Our results indicate that 63.56% of the drug responses are achieved even in the placebo groups. In light of these strong placebo responses, future studies should investigate how to exploit placebo mechanisms in clinical practice.


para-Hydrogenation of unsaturated moieties on poly(lysine) derived substrates for the development of novel hyperpolarized MRI contrast agents.
Four alkyne-functionalized poly(lysine) derivatives have been synthesized and characterized by 1H and 13C NMR spectroscopy. In the first poly(lysine) derivative, phenylpropiolate moieties are directly bound to the aminic arms, whereas in the other derivatives, propargylamine moieties are bound to the aminic poly(lysine) arms through glucaric acid and diethylene glycol (DG) chains, respectively. para-Hydrogenation of the alkyne-functionalized poly(lysine) compounds has been investigated and the results have been discussed in terms of spin lattice relaxation properties of the hydrogenated products. It is shown that the longer the mobile chain separating the unsaturation from the poly(lysine) backbone, the more intense the polarized signals when para-hydrogenation is carried out. This is due to (a) the maintenance of short reorientational times on the unsaturated ends, and therefore a sufficiently long T(1) of the protons added during hydrogenation, and (b) the minor effect of steric hindrance by the poly(lysine) backbone that decreases interaction of the unsaturation with the catalyst, allowing higher hydrogenation rates.


Pirfenidone-induced Eosinophilic Pleurisy.
The patient was a 69-year-old man with idiopathic pulmonary fibrosis who was taking pirfenidone. After 7 weeks of treatment, he suffered from left-sided eosinophilic pleurisy. Medical thoracoscopy was performed and the histopathological examination of the parietal pleura revealed the massive infiltration of eosinophils and lymphoid follicles. After stopping pirfenidone therapy, the patient's pleural effusion disappeared without additional treatment, and never recurred. This is the first case report of pirfenidone-induced pleurisy.


[177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent.
Purpose: Based on the clinical relevance of the chemokine receptor 4 (CXCR4) as a molecular target in cancer and on the success of [68Ga]pentixafor as an imaging probe for high-contrast visualization of CXCR4-expression, the spectrum of clinical CXCR4-targeting was expanded towards peptide receptor radionuclide therapy (PRRT) by the development of [177Lu]pentixather. Experimental design: CXCR4 affinity, binding specificity, hCXCR4 selectivity and internalization efficiency of [177Lu]pentixather were evaluated using different human and murine cancer cell lines. Biodistribution studies (1, 6, 48, 96h and 7d p.i.) and in vivo metabolite analyses were performed using Daudi-lymphoma bearing SCID mice. Extrapolated organ doses were cross-validated with human dosimetry (pre-therapeutic and during [177Lu]pentixather PRRT) in a patient with multiple myeloma (MM). Results: [177Lu]pentixather binds with high affinity, specificity and selectivity to hCXCR4 and shows excellent in vivo stability. Consequently, and supported by >96% plasma protein binding and a logP=-1.76, delaying whole-body clearance of [177Lu]pentixather, tumor accumulation was high and persistent, both in the Daudi model and the MM patient. Tumor/background ratios (7d p.i.) in mice were 499±202, 33±7, 4.0±0.8 and 116±22 for blood, intestine, kidney and muscle, respectively. In the patient, high tumor/kidney and tumor/liver dose ratios of 3.1 and 6.4 were observed during [177Lu]pentixather PRRT (7.8 GBq), with the kidneys being the dose-limiting organs. Conclusions: [177Lu]pentixather shows excellent in vivo CXCR4-targeting characteristics and a suitable pharmacokinetic profile, leading to high tumor uptake and retention and thus high radiation doses to tumor tissue during PRRT, suggesting high clinical potential of this [68Ga]pentixafor/[177Lu]pentixather based CXCR4-targeted theranostic concept.


Effects of resting heart rate on blood pressure and hypertension in Chinese children: findings from blood pressure surveillance program.
The purpose of this study was to analyze the association between resting heart rate (RHR) and prevalence of hypertension in Chinese children and to identify if this association was mediated by body mass index (BMI). The data of 5445 children who participated in the Blood Pressure Surveillance Program (2011-2017) were analyzed in this study. Children were divided into four groups according to quartiles of RHR in boys and girls, respectively. Compared to those in the first quartile, boys and girls in the fourth quartile were 3.06 (95% CI 2.12, 4.41) and 4.94 (95% CI 3.21, 7.61) times more likely to have hypertension, respectively. Meanwhile, every 10 beats per minute (bpm) increase in RHR was associated with a 41% (95% CI 1.27, 1.56) and 66% (95% CI 1.49, 1.85) greater risk of hypertension in boys and girls, respectively. There were no significant interactions between RHR and BMI on the prevalence of hypertension. This study confirms the existence of a relationship between elevated RHR and increased risk of hypertension in children, independent of BMI. An elevated RHR could be considered as a risk factor for the risk assessment of hypertension, no matter from a clinical setting or a public health perspective.


[Factors associated with the occurrence of influenza A virus infections in fattening swine].
In August of 1989 sera from 2115 finishing pigs out of 214 herds in the north of Schleswig- Holstein (Germany) were tested for antibodies against three strains of Influenza A viruses by using the haemagglutination inhibition test. Seroprevalences of A/Swine/Nederland/25/80 (H1N1), A/Philippines/2/82 (H3N2), and A/Port Chalmers/1/73 (H3N2) on herd level were 23.4%, 20.6% and 5.1% respectively. The mean within herd prevalences were 9.6%, 14.7% and 0.6%, respectively. Antibodies against H1N1 and H3N3 strains were simultaneously found in 7.5% of the herds and in 1.6% of the pigs. In 485 (22.9%) of the pigs and in 83 (38.3%) of the herds at least one of the strains was prevalent. In 61 (73.5%) of those herds there was no evidence of a clinical outbreak before testing. A higher risk of infection with influenza virus was associated with high pig density (> or = 200 pigs per km2) and with management factors as greater herd size (> 300 finishing pigs), slatted floors (compared to straw bedding) and all in-all out system (compared to continuous purchase).


Fatal Mycobacterium colombiense/cytomegalovirus coinfection associated with acquired immunodeficiency due to autoantibodies against interferon gamma: a case report.
Reports of acquired immunodeficiency due to autoantibodies against interferon gamma in the adult population are increasing. The interleukin-12-dependent interferon-gamma axis is a major regulatory pathway of cell-mediated immunity and is critical for protection against a few intracellular organisms, including non-tuberculous mycobacteria and Salmonella spp. We report the first case of a fatal disseminated Mycobacterium colombiense/cytomegalovirus coinfection in an adult woman associated with the acquisition of autoantibodies against interferon-gamma. A 49-year-old woman, born to nonconsanguineous parents in Laos, but who had lived in Canada for the past 30 years, presented with a 1-month history of weight loss, fatigue, cough, and intermittent low-grade fever. A thoracic computed tomography scan revealed an 8 × 7 cm irregular mass impacting the right superior lobar bronchus along with multiple mediastinal and hilar adenopathies. On the fourth day of admission, the patient developed fever with purulent expectorations. Treatment for a post-obstructive bacterial pneumonia was initiated while other investigations were being pursued. Almost every culture performed during the patient's hospitalization was positive for M. colombiense. Given the late presentation of symptoms - at the age of 49 years - and the absence of significant family or personal medical history, we suspected an acquired immunodeficiency due to the presence of anti-interferon-gamma autoantibodies. This was confirmed by their detection at high levels in the plasma and a STAT1 phosphorylation assay on human monocytes. The final diagnosis was immunodeficiency secondary to the production of autoantibodies against interferon-gamma, which resulted in a post-obstructive pneumonia and disseminated infection of M. colombiense. The clinical course was complicated by the presence of a multiresistant Pseudomonas aeruginosa post-endobronchial ultrasound mediastinitis, cytomegalovirus pneumonitis with dissemination, and finally, susceptible P. aeruginosa ventilator-associated pneumonia with septic shock and multiple organ failure, leading to death despite appropriate antibacterial and anti-mycobacterial treatment. Although rare, acquired immunodeficiency syndromes should be considered in the differential diagnosis of patients with severe, persistent, or recurrent infections. Specifically, severe non-tuberculous mycobacteria or Salmonella infections in adults without any other known risk factors may warrant examination of autoantibodies against interferon-gamma because of their increasing recognition in the literature.


Psychiatric symptom dimensions in the Cornell Medical Index among normal adult males.
Factor analysis of items from the psychiatric portion of the Cornell Medical Index (CMI) was performed to determine the empirical symptom dimensions in a sample of 1682 normal adult males. Six factors were extracted and interpreted as Irritability, Inability to Cope, Depression, Timidity, Normal Anxiety, and Clinical Anxiety. The factors showed some correspondence to the clinical groupings in the CMI and to factors discovered in other studies. Whiel all showed small positive correlations with a measure of Neuroticism, the consistency of these results argues against the hypothesis that the CMI M-R sections measure only a urinary factor of neurotic complaining. Some modifications in the CMI are recommended that could emhance its utility as a diagnostic or personality instrument.


Participation in an Older Adult Heart Health Program affects lifestyle behavior.
The Older Adult Heart Health Program (HHP) was a university-based outreach health screen and education program. The purpose of this study was to determine whether the HHP was associated with lifestyle behavior change among participants. HHP volunteers (n=136) were mostly white (98.5%) women (79.4%) with a mean (+/- SEM) age of 75.1+/-0.6 years. A follow-up survey was sent to the participants' homes 4 months after the HHP inquiring about physician office visitation and adoption of healthy lifestyle behaviors since the HHP. A majority (n=60, 64.5%) of those who completed the survey (n=93, 68.4% response rate) indicated they visited their physician after the HHP. A greater percentage of survey respondents who visited their physician made lifestyle behavior changes than those who did not, 71.1% vs. 45.4%, respectively (p=0.032). These findings suggest participating in programs such as the HHP prompt physician visitation and behavior change among older adults residing in the community.