c-Myc initiates illegitimate replication of the ribonucleotide reductase R2 gene.
The mechanisms through which the oncoprotein c-Myc initiates locus-specific gene amplification are not understood. When analysing the initiation mechanism of c-Myc-dependent amplification of the mouse ribonucleotide reductase R2 (R2) gene, we observe c-Myc-dependent initiation of illegitimate DNA replication of the R2 gene. We demonstrate multiple simultaneous c-Myc-induced R2 replication forks, whereas R2 normally replicates with a single fork. In contrast, cyclin C replicates with only a single replication fork irrespective of c-Myc deregulation. In addition to de novo replication forks, c-Myc also initiates bi-allelic replication of R2, abrogating its normal mono-allelic replication pattern. Moreover, several chromosomal regions also display c-Myc-induced illegitimate replication profiles. Thus, c-Myc can act as an illegitimate replication-licensing factor that promotes de novo replication initiation and illegitimate replication timing that adversely impacts upon genomic stability.


Species-specific DNA probe and development of a quantitative PCR assay for the detection of Morganella morganii.
To develop a SYBR Green quantitative PCR assay (qPCR) for the specific detection of Morganella morganii, a fish pathogen responsible for the Histamine Fish Poisoning. A new primer set, amplifying a 179-bp fragment of the 16S rRNA gene, was selected for specificity, and 14 M. morganii strains and 32 non-Morganella strains were evaluated. The melting temperature of 84°C was consistently specific for the amplicon. Two standard curves were constructed: the minimum detection sensitivity was 0·563 pg of pure DNA, corresponding to DNA extracted from nine cells of M. morganii. The qPCR assay was evaluated in experiments with seeded fish samples, and the regression coefficient values were calculated. A highly specific and rapid assay was developed for the detection of M. morganii in tuna fish samples. This method represents the first study about the quantification of pathogenic M. morganii in fish products. This approach can be utilized to prevent the presence of this undesirable species in the food chain.


Comparison of two ultrashort echo time sequences for the quantification of T1 within phantom and human Achilles tendon at 3 T.
Ultrashort echo time (UTE) techniques enable direct imaging of musculoskeletal tissues with short T2 allowing measurement of T1 relaxation times. This article presents comparison of optimized 3D variable flip angle UTE (VFA-UTE) and 2D saturation recovery UTE (SR-UTE) sequences to quantify T1 in agar phantoms and human Achilles tendon. Achilles tendon T1 values for asymptomatic volunteers were compared to Achilles tendon T1 values calculated from patients with clinical diagnoses of spondyloarthritis (SpA) and Achilles tendinopathy using an optimized VFA-UTE sequence. T1 values from phantom data for VFA- and SR-UTE compare well against calculated T1 values from an assumed gold standard inversion recovery spin echo sequence. Mean T1 values in asymptomatic Achilles tendon were found to be 725±42 ms and 698±54 ms for SR- and VFA-UTE, respectively. The patient group mean T1 value for Achilles tendon was found to be 957±173 ms (P<0.05) using an optimized VFA-UTE sequence with pulse repetition time of 6 ms and flip angles 4, 19, and 24°, taking a total 9 min acquisition time. The VFA-UTE technique appears clinically feasible for quantifying T1 in Achilles tendon. T1 measurements offer potential for detecting changes in Achilles tendon due to SpA without need for intravenous contrast agents.


Evidence for Accelerated Biological Aging in Young Adults with Prader-Willi Syndrome.
Adults with Prader-Willi syndrome (PWS) are at increased risk of developing age-associated diseases early in life and, like in premature aging syndromes, aging might be accelerated. We investigated leukocyte telomere length (LTL), a marker of biological age, in young adults with PWS and compared LTL to healthy young adults of similar age. As all young adults with PWS were treated with growth hormone (GH), we also compared LTL in PWS subjects to GH-treated young adults born short for gestational age (SGA). Cross-sectional study in age-matched young adults; 47 with PWS, 135 healthy, and 75 born SGA. LTL measured by quantitative polymerase chain reaction, expressed as telomere/single copy gene ratio. Median (interquartile range) LTL was 2.6 (2.4-2.8) at a median (interquartile range) age of 19.2 (17.7-21.3) years in PWS, 3.1 (2.9-3.5) in healthy young adults and 3.1 (2.8-3.4) in the SGA group. Median LTL in PWS was significantly lower compared to both control groups (P < .01). In PWS, a lower LTL tended to be associated with a lower total IQ (r = 0.35, P = .08). There was no association between LTL and duration of GH treatment, cumulative GH dose, or several risk factors for type 2 diabetes mellitus or cardiovascular disease. Young adults with PWS have significantly shorter median LTL compared to age-matched healthy young adults and GH-treated young adults born SGA. The shorter telomeres might play a role in the premature aging in PWS, independent of GH. Longitudinal research is needed to determine the influence of LTL on aging in PWS.


Extraction of biologic particles by pumping effect in a pi-shaped ultrasonic actuator.
This paper presents a new method of extracting biologic particles from a mixture of particles. The method is based on the pumping effect in a pi-shaped ultrasonic actuator, which has a gap between its two vibrating metal plates. An adhesive tape is placed at a proper position in the gap. Due to the pumping effect which is induced by the sound field in the gap, the particles with smaller mass and radius in the mixture can be pumped up to reach the adhesive tape; while the ones with larger mass cannot. Therefore, the particles with smaller mass and radius can be extracted from the mixture. A theoretical model which can well explain the operation principle and experimental phenomena is developed. By the experimental results and the theoretical analyses based on the model, the validity of the method in extracting small particles from a mixture of solid particles in air is confirmed, and the effects of the actuator's vibration, adhesive tape height, contents of the mixture and viscosity of fluid on the extraction are clarified. Also, it is theoretically predicted that the method will work under the microgravity condition in air.


Interaction of an intercalating antitumoral agent: 9-hydroxy-2-methyl ellipticinium (NMHE) with chromatin.
In this work we study the effects of an intercalating antitumoral agent: 9-hydroxy-2-methyl ellipticinium (NMHE) on the structure of chromatin, using micrococcal nuclease and DNase 1 as structural probes. The binding of the drug to chromatin, either in vitro or in the nuclei, induces two structural changes of chromatin: (a) an unfolding of the overall structure which results in an activation of the rate of degradation of chromatin by micrococcal nuclease and (b) a disorganisation of the core particle structure leading to the unwrapping of the DNA from the histone core. Moreover, by studying the interaction of MMHE with nuclei labeled in the active regions of the genome through a nick-translation reaction, it appears that the drug is overconcentrated in these regions and does not induce any new structural changes. The interaction of NMHE with DNase 1-sensitive regions of chromatin indicates that these regions are already "open" or relaxed and represent a preferential target for the drug.


Genomic analyses reveal three phylogenetic species and their evolutionary histories in the big-headed turtle.
The critically endangered big-headed turtle (Platysternon megacephalum) is currently classified into three subspecies. However, the classification is still controversial and their evolutionary histories are still unclear. Here, multiple genetic analyses consistently revealed three phylogenetic groups with substantial genetic divergences and distinct demographic histories, suggesting three phylogenetic species (P. megacephalum, P. peguense, and Baise clade). Phylogeographical analyses revealed that the Red River plains and Guangxi basins are largely coincident with the boundaries between the three phylogenetic species, highlighting the key role of lowland areas in driving speciation in the big-headed turtle. The Baise clade is characterized by high-linkage disequilibrium but the lowest effective population size, indicating that the cryptic phylogenetic species is more vulnerable to human activities and environmental disturbance, and urgently needs more protection. Our findings provide fundamental insights into the taxonomy and scientific conservation of the family Platysternidae.


Deep intronic mutation in CRTAP results in unstable isoforms of the protein to induce type I collagen aggregation in a lethal type of osteogenesis imperfecta type VII.
Genetic mutations are involved in Mendelian disorders. Unbuffered intronic mutations in gene variants can generate aberrant splice sites in mutant transcripts, resulting in mutant isoforms of proteins with modulated expression, stability, and function in diseased cells. Here, we identify a deep intronic variant, c.794_1403A>G, in CRTAP by genome sequencing of a male fetus with osteogenesis imperfecta (OI) type VII. The mutation introduces cryptic splice sites in intron-3 of CRTAP, resulting in two mature mutant transcripts with cryptic exons. While transcript-1 translates to a truncated isoform (277 amino acids) with thirteen C-terminal non-wild-type amino acids, transcript-2 translates to a wild-type protein sequence, except that this isoform contains an in-frame fusion of non-wild-type twenty-five amino acids in a tetratricopeptide repeat sequence. Both mutant isoforms of CRTAP are unstable due to the presence of a unique 'GWxxI' degron, which finally leads to loss of proline hydroxylation and aggregation of type I collagen. Although type I collagen aggregates undergo autophagy, the overall proteotoxicity resulted in death of the proband cells by senescence. In summary, we present a genetic disease pathomechanism by linking a novel deep intronic mutation in CRTAP to unstable mutant isoforms of the protein in lethal OI type VII.


Intraventricular infusion of quinolinic acid impairs spatial learning and memory in young rats: a novel mechanism of lead-induced neurotoxicity.
Lead (Pb), a heavy metal, and quinolinic acid (QA), a metabolite of the kynurenine pathway of tryptophan metabolism, are known neurotoxicants. Both Pb and QA impair spatial learning and memory. Pb activates astrocytes and microglia, which in turn induce the synthesis of QA. We hypothesized increased QA production in response to Pb exposure as a novel mechanism of Pb-neurotoxicity. Two experimental paradigms were used. In experiment one, Wistar rat pups were exposed to Pb via their dams' drinking water from postnatal day 1 to 21. Control group was given regular water. In the second protocol, QA (9 mM) or normal saline (as Vehicle Control) was infused into right lateral ventricle of 21-day old rats for 7 days using osmotic pumps. Learning and memory were assessed by Morris water maze test on postnatal day 30 or 45 in both Pb- and QA-exposed rats. QA levels in the Pb exposed rats were measured in blood by ELISA and in the brain by immunohistochemistry on postnatal days 45 and 60. Expression of various molecules involved in learning and memory was analyzed by Western blot. Means of control and experimental groups were compared with two-way repeated measure ANOVA (learning) and t test (all other variables). Pb exposure increased QA level in the blood (by ~ 58%) and increased (p < 0.05) the number of QA-immunoreactive cells in the cortex, and CA1, CA3 and dentate gyrus regions of the hippocampus, compared to control rats. In separate experiments, QA infusion impaired learning and short-term memory similar to Pb. PSD-95, PP1, and PP2A were decreased (p < 0.05) in the QA-infused rats, whereas tau phosphorylation was increased, compared to vehicle infused rats. Putting together the results of the two experimental paradigms, we propose that increased QA production in response to Pb exposure is a novel mechanism of Pb-induced neurotoxicity.


Comparative in vivo metabolism of 6-[18F]fluoro-L-dopa and [3H]L-dopa in rats.
In vivo double-label experiments in rats were designed to correlate the peripheral and cerebral metabolism of 6-[18F]fluoro-L-DOPA [( 18F]FDOPA) with that of [3H]L-DOPA. Authentic samples of the major [18F]FDOPA metabolites were synthesized to identify the 18F-labeled metabolites. After carbidopa pretreatment and intravenous administration of the compound, the products of peripheral metabolism in plasma were analyzed at times from 3 to 60 min. In the periphery, amine conjugates were detected but they accounted for less than 15% of the total radioactivity; the major metabolites were 3-O-methyl-6-[18F]fluoro-L-DOPA and 3-O-methyl-[3H]L-DOPA. The rate and extent of 3-O-methylation of [18F]FDOPA exceeded that of [3H]L-DOPA. Both 3-O-methylated products entered the striatum and cerebellum where they contributed significant but uniform activity. Analysis of cerebral metabolism in these structures indicated a linear accumulation of total radioactivity: a striatum/cerebellum ratio of 2 was observed by 60 min. 6-[18F]Fluorodopamine (35%) and [3H]dopamine (55%) were the major metabolites formed in the striatum: however, the methylated [18F]FDOPA and [3H]DOPA products of predominantly peripheral origin represented 55% (18F) and 35% (3H) of the total radioactivity respectively. Other [3H]dopamine metabolites and their 18F-labeled analogs represented less than 10-15% at all times analyzed. The cerebellum radioactivity was composed only of [18F]FDOPA, [3H]DOPA and their 3-O-methylated products. These data will serve as the basis for the development of kinetic models of [18F]FDOPA metabolism that can be applied to the evaluation of central dopamine biochemistry with positron emission tomography in humans.


Poly(ethylene oxide) facilitates the characterization of an affinity between strongly basic proteins with DNA by affinity capillary electrophoresis.
In order to study kin17 protein-DNA affinity, we have developed a fast and reproducible capillary electrophoresis (CE) analysis of a strongly basic protein: kin17 protein, using a nonpermanent coating based on poly(ethylene oxide) (PEO) to avoid adsorption of kin17. The coating procedure was optimized to provide a residual and stable electroosmotic flow (EOF = 5 x 10(-5) cm(2)/V x s), exhibiting RSD of 0.3% and excellent long-term stability. Good intraday and interday reproducibility of kin17 migration times (0.8 and 0.3% relative standard deviation (RSD), respectively) enabled us to consider that the recovery percentage obtained for kin17 protein was satisfactory (79%). The potential of this PEO-based coating procedure was evaluated for affinity CE method in order to study the affinity of kin17 protein for two single-stranded DNA (ssDNA) models: polydeoxyadenylic acid and polydeoxycytidilic acid (pdA and pdC). Binding constants (1.5 x 10(7) +/- 17% and 1.7 x 10(7) + 25%M(-1)) were evaluated assuming a 1:1 affinity between kin17 and pdA or pdC, respectively.


A modified Holzapfel-Ogden law for a residually stressed finite strain model of the human left ventricle in diastole.
In this work, we introduce a modified Holzapfel-Ogden hyperelastic constitutive model for ventricular myocardium that accounts for residual stresses, and we investigate the effects of residual stresses in diastole using a magnetic resonance imaging-derived model of the human left ventricle (LV). We adopt an invariant-based constitutive modelling approach and treat the left ventricular myocardium as a non-homogeneous, fibre-reinforced, incompressible material. Because in vivo images provide the configuration of the LV in a loaded state even in diastole, an inverse analysis is used to determine the corresponding unloaded reference configuration. The residual stress in this unloaded state is estimated by two different methods. One is based on three-dimensional strain measurements in a local region of the canine LV, and the other uses the opening angle method for a cylindrical tube. We find that including residual stress in the model changes the stress distributions across the myocardium and that whereas both methods yield qualitatively similar changes, there are quantitative differences between the two approaches. Although the effects of residual stresses are relatively small in diastole, the model can be extended to explore the full impact of residual stress on LV mechanical behaviour for the whole cardiac cycle as more experimental data become available. In addition, although not considered here, residual stresses may also play a larger role in models that account for tissue growth and remodelling.


Making sense of the venous leg ulcer debate: a literature review.
Venous leg ulcers cause patients much distress. Treating them is expensive, with many hidden costs. As understanding of the causes and development of this condition improves, debate over the best treatments or treatment combinations is growing.


Speech and language assessment scales of deaf children.
Six year old deaf children with an average PTA of 105.7 dB were evaluated for speech and language skills using rating scales. Five rating scales were designed to assess language production, sign ability, overall communication skills, speech reception and speech intelligibility. Each scale incorporated five categories ranging from inability to complete ability to demonstrate a given skill. For several ratings, classroom teachers, given instruction, were asked to make judgments which were later correlated with examiner's scores, Mean ratings indicate that comprehension skills superceded performance skills. A hierarchy of ability among communication skills can be seen.


Core 2 oligosaccharide biosynthesis distinguishes between selectin ligands essential for leukocyte homing and inflammation.
Mammalian serine/threonine-linked oligosaccharides (O-glycans) are commonly synthesized with the Golgi enzyme core 2 beta-1,6-N-acetylglucosaminyltransferase (C2 GlcNAcT). Core 2 O-glycans have been hypothesized to be essential for mucin production and selectin ligand biosynthesis. We report that mice lacking C2 GlcNAcT exhibit a restricted phenotype with neutrophilia and a partial deficiency of selectin ligands. Loss of core 2 oligosaccharides reduces neutrophil rolling on substrata bearing E-, L-, and P-selectins and neutrophil recruitment to sites of inflammation. However, the diminished presence of L-selectin ligands on lymph node high endothelial venules does not affect lymphocyte homing. These studies indicate that core 2 oligosaccharide biosynthesis segregates the physiologic roles of selectins and reveal a function for the C2 GlcNAcT in myeloid homeostasis and inflammation.


Mastoid recurrence after radiotherapy for nasopharyngeal carcinoma: two case studies.
The mastoid is a rare site of nasopharyngeal carcinoma recurrence after radiotherapy, and no relevant reports are currently in the literature. Two case reports are presented describing patients with a history of nasopharyngeal carcinoma who received primary radical radiotherapy. The first was treated by conventional radiotherapy, using 2-dimensional techniques, while the second was delivered by intensity-modulated radiation therapy (IMRT). The patients presented with progressive mastoid recurrence after radiotherapy at 12 and 16 months, respectively. Clinical presentation of mastoid recurrence was similar to mastoiditis. Meanwhile, distant metastasis occurred in both cases. To date, 1 has died of distant metastasis, and the other is alive with disease stabilization following chemotherapy treatment. This is the first report of mastoid recurrence after radiotherapy for nasopharyngeal carcinoma, which should alert clinicians to probe into the pathogenesis and pay attention to the relationship between mastoid recurrence and distant metastasis.


Vascular endothelial growth factor gene polymorphisms in North Indian patients with end stage renal disease.
Vascular endothelial growth factor (VEGF) is involved in the development and differentiation of the vascular system. VEGF is expressed constitutively by epithelial cells from embryonic to adult kidneys and may play a key role in progression of kidney diseases. It is required for the growth and proliferation of glomerular and peritubular endothelial cells. In the kidney VEGF expression is prominently found in glomerular podocytes and in tubular epithelial cells, while VEGF receptors are mainly seen on preglomerular, glomerular, and peritubular endothelial cells. We have investigated the role of VEGF gene polymorphisms (-2578C/A,-2549 18 bp I/D, -1154 G/A and +936 C/T) as a susceptibility marker for end stage renal disease (ESRD). We genotyped VEGF gene polymorphism in three hundred patients and three hundred and fifty ethnically matched unrelated healthy controls free from any renal disease. These markers were studied using ARMS-PCR and PCR-RFLP methods. Patients were categorized on the basis of the histo-pathological subtypes into chronic glomerulonephritis (CGN=109), hypertensive nephrosclerosis (HTN=106) and chronic interstitial nephritis (CIN=60). VEGF -2578C and -2549D alleles were found to be ESRD causative alleles. It was observed that there was significant differences in the frequencies of the T allele of +936C/T polymorphism among CGN, HTN and CIN respectively. VEGF -1154AA genotype and A allele were associated significantly with CGN. T-G-A-D, T-A-C-I,C-G-A-D,C-A-C-D,C-G-C-I,C-A-A-D and T-G-C-D were seven haplotypes concurred in all the ESRD patients irrespective of underlying disease. While C-G-C-D & C-G-A-I haplotypes showed risk association in CGN & CIN, C-A-C-I was observed to play predisposing role in HTN. The results highlight the role of studied VEGF polymorphisms in end stage renal disease at large and subsequently in the three primary kidney diseases among the North Indian population.


The site of 25-hydroxycholecalciferol stimulated protein synthesis in the rat kidney.
Autoradiographs of the kidneys of rachitic rats dosed in vivo with 250 pmoles 25-hydroxycholecaliferol (25-OHD3) and 3H-leucine showed increased grain counts in portions of proximal renal tubules. On incubation of kidney slices the synthesis of only 1 cytosol protein was found to be stimulated by the steroid. On disc gel electrophoresis it had the characteristics of renal calcium binding protein.


Bacterial porins: structure and function.
Within the class of integral membrane proteins, the bacterial porins display a remarkable resistance to denaturants and proteases. This stability is probably crucial for the formation of highly ordered, three-dimensional crystals. Structural analysis of these crystals has been possible in atomic detail. This analysis has revealed interesting features, such as the aromatic girdles, and has helped to explain several observations, including the porins' ability to discriminate between polar and non-polar solutes. Recent research has thus improved our understanding of the porins in a qualitative fashion.


Estimation of radiation exposure in 16-detector row computed tomography of the heart with retrospective ECG-gating.
We sought to evaluate the radiation exposure of cardiac CT scans with 16-row multidetector computed tomography (MDCT). Additionally the possibility of dose reduction by using a ECG-controlled tube current modulation technique was evaluated. An Alderson Rando phantom equipped with thermoluminescent dosimeters was used for dose measurements. Effective dose was calculated according to ICRP 60. Exposure was performed on a 16-row MDCT scanner with standard protocols for CT coronary calcium scoring (120 kV, 133 mAs, 12 x 1.5 mm) and CT coronary angiography (120 kV, 400 mAs, 12 x 0.75 mm). Exposure was repeated at a simulated heart rate of 60 bpm with ECG-pulsed tube current modulation. Effective dose was 2.9 mSv (male) and 3.6 mSv (female) for the calcium scoring protocol. CT coronary angiography resulted in an effective dose of 8.1 mSv (male) and 10.9 mSv (female). Using ECG-pulsed tube current modulation radiation exposure can significant reduced: by 46 % (1.6 mSv) in calcium scoring and by 47 % (4.3 mSv) in CT coronary angiography. MDCT of the heart shows a significant radiation exposure, which can significantly be reduced by ECG-pulsed tube current modulation. Radiation exposure of cardiac MDCT is comparable to CT-examinations of chest or abdomen, but seem to be slightly higher compared to conventional coronary angiography.


Unveiling the role of activated carbon on hydrolysis process in anaerobic digestion.
Conventionally, activated carbon is widely applied in water treatment systems due to its capability of adsorbing inhibitors or stimulating methanogenesis rate. This study demonstrates that powder activated carbon (PAC) also stimulate hydrolysis in anaerobic digestion (AD) of thermal hydrolysis pretreated sludge. This is evidenced with 0.95-1.42 times higher methane generation, 12.46-20.06% higher volatile solids removal and greater refractory compounds degradation stimulated by PAC. Functional prediction reveals that genes coding hydrolytic enzymes and xenobiotics metabolism were highly expressed with the presence of PAC. Furthermore, the stimulated hydrolysis activity was effectively maintained at PAC concentration as low as 0.125 g/L, though methanogenesis rate reduced by 80.30% compared to 1 g/L case. This study reports the role of activated carbon on the hydrolysis which has been ignored previously and the impact of PAC on AD performance in long-term operation. The results improve understanding on the true function of PAC in AD system.


Estimating the superiority of a drug to a placebo when all and only those patients at risk are treated with the drug.
It is shown that, under certain assumptions, one can estimate the difference between the effect of a treatment and that of a placebo even when the treatment has been given to all and only those patients who are at risk (as evidenced by a screening examination).


Three-dimensional live imaging of Atoh1 reveals the dynamics of hair cell induction and organization in the developing cochlea.
During cochlear development, hair cells (HCs) and supporting cells differentiate in the prosensory domain to form the organ of Corti, but how one row of inner HCs (IHCs) and three rows of outer HCs (OHCs) are organized is not well understood. Here, we investigated the process of HC induction by monitoring Atoh1 expression in cochlear explants of Atoh1-EGFP knock-in mouse embryos and showed that only the cells that express Atoh1 over a certain threshold are selected for HC fate determination. HC induction initially occurs at the medial edge of the prosensory domain to form IHCs and subsequently at the lateral edge to form OHCs, while Hedgehog signaling maintains a space between IHCs and OHCs, leading to formation of the tunnel of Corti. These results reveal dynamic Atoh1 expression in HC fate control and suggest that multi-directional signals regulate OHC induction, thereby organizing the prototype of the organ of Corti.


Effects of carbonation and leaching on porosity in cement-bound waste.
Porosity is possibly an important parameter with respect to leaching of constituents from cement monoliths. During its lifetime, the pore structure of cementitious matrices changes due to carbonation and leaching. This paper discusses the effects of both accelerated carbonation and continuous leaching on the porosity, and, conversely, how porosity affects leaching properties. Two sample types are investigated: a mortar with MSWI-bottom ash substituting the sand fraction and a cement paste with 30 wt% of the cement substituted by a flue gas cleaning residue. The samples have been intensively carbonated in a 20% CO(2) atmosphere for up to 60 days and were subsequently leached. The porosity was investigated by mercury intrusion porosimetry. Accelerated carbonation decreases total porosity by 12% in the case of 60 days of treatment of bottom ash mortars, whereas continuous leaching during 225 days increases it by 16%. Both carbonation and leaching decrease the amount of smaller capillary pores. Carbonation decreases both porosity and pH. Decreasing porosity diminishes leaching of sodium and potassium, while the decrease in pH increases leaching. However, the former process dominates the latter, resulting in a net decreasing effect of carbonation on the release of sodium and potassium from these cement matrices.


Racial/Ethnic Differences in the Use of Primary Care Providers and Preventive Health Services at a Midwestern University.
Many universities seek to improve the health and wellbeing of their faculty and staff through employer wellness programs but racial/ethnic disparities in health care use may still persist. The purpose of this research was to identify racial/ethnic disparities in the use of preventive health services at a Midwestern university. A record review was conducted of self-reported health data from University employees, examining the use of primary care and common screening procedures collected in a Personal Health Assessment conducted by the University's wellness program. Results show that there were significant racial/ethnic differences in the use of primary care and participation in screening. Notably, Asian employees in this sample were less likely to have a primary care provider and participate in routine cancer screenings. The observed racial/ethnic differences in screening behavior were mediated by the use of primary care. Together, these data show that despite equal access to care, racial and ethnic disparities in screening persist and that having a primary care provider is an important predictor of screening behavior. Results suggest that health communications designed to increase screening among specific racial/ethnic minority groups should target primary care use.


Dissemination of antibiotics through the wastewater-soil-plant-earthworm continuum.
Under the ongoing climate change scenario, treated municipal wastewater (TMW) is a potential candidate for irrigated agriculture but may result in the exposure of agricultural environments to antibiotics. We studied the transfers of trimethoprim, sulfamethoxazole, and sulfapyridine in the TMW-soil-plant-earthworm continuum under greenhouse/laboratory conditions. Irrigation of potted spinach and radish with as-collected TMW resulted in no transfers of antibiotics into soil or plants owing to their low concentrations in the tertiary-treated TMW. However, TMW spiked with higher antibiotic concentrations led to transfers through this continuum. High initial inputs, slow soil degradation, and chemical speciation of the antibiotics, coupled with an extensive plant-root distribution, were important factors enhancing the plant uptake of antibiotics. In microcosm studies, transfers from vegetable materials into earthworms were low but showed potential for bioaccumulation. Such food chain transfers of antibiotics may be a driver for antibiotic resistance in agricultural systems, which is an area worthy of future study. These issues can perhaps be mitigated through high levels of TMW purification to effectively remove antibiotic compounds.


Long-term drug treatment of asthma in children.
In this short review the pharmacologic and clinical effect of antiasthma drugs in children that is, beta 2-agonists, theophylline, anticholinergics, disodiumcromoglycate/nedocromil sodium, and inhaled corticosteroids are described. Furthermore, a medication plan for maintenance treatment is presented.


Changes in haemodynamics and left ventricular function during intravenous nifedipine infusion with and without additional propranolol in patients with coronary artery disease. A randomized, placebo controlled trial.
The haemodynamic effects of a combined intravenous treatment of nifedipine and propranolol in ten patients with coronary artery disease compared to a single treatment with nifedipine or placebo were investigated. Nifedipine infusion resulted in a reduction of left ventricular (LV) afterload and LV volumes with an increase in heart rate and EF and no change of the double product, coronary sinus flow, LV diastolic parameters and dp/dtmax. Addition of propranolol lowers myocardial oxygen demand by reducing heart rate and dp/dtmax together with a sustained afterload reduction with no change in LV volumes and EF. The vasodilatatory action of nifedipine pretreatment balanced the negative effects of acute beta-receptor blockade on LV function and allows the reduction of myocardial oxygen demand without a deterioration of LV function.


Purification and properties of two blue biliproteins from the larval hemolymph and integument of Rhodinia fugax (Lepidoptera: Saturniidae).
Blue biliproteins (BPs) are found in the hemolymph and integument of the fifth instar larvae of the saturniid silkworm, Rhodinia fugax. An efficient method of isolating BPs from the hemolymph, epidermis and cuticle using hydrophobic interaction chromatography and ion-exchange chromatography was devised. The BPs from the hemolymph, epidermis and cuticle have molecular weights of approximately 24,000, 48,000 and 23,000 Da by gel-filtration, respectively. Using matrix-assisted laser desorption ionization-time of flight/mass spectrometry (MALDI-TOF/MS), the respective molecular masses were determined to be 22,641, 22,908 and 22,737 Da. Based on these results, BP molecules from the hemolymph and cuticle are assumed to be monomers, whereas the epidermal BP is a dimer. The amino acid composition and N-terminal amino acid sequences of the BPs from the hemolymph and cuticle (BP-I) are very similar, but the BP from the epidermis (BP-II) is quite different. The N-terminal amino acid sequences of these BPs share approximately 50% identity with the biliproteins from other lepidopteran insects. The blue color of BP is due to the presence of bile pigments, which are non-covalently bound to the apoprotein. The absorbance spectrum of BP-I from the hemolymph revealed maxima at 280 and 669 nm, while that of BP-II showed maxima at 280, 385 and 663 nm. The pigment dimethyl esters were extracted from BP-I and BP-II with acidic methanol and dichloromethane. The results of these analyses suggest that the blue pigments of BP-I and BP-II are different; BP-I contains a phorcabilin-like pigment while BP-II contains biliverdin IX gamma. In an immunoblot analysis, anti-BP-I antibodies, produced against hemolymph BP-I, reacted with immunoreactive proteins in the hemolymph and cuticle of R. fugax. These anti-BP-I antibodies did not react with BP-II and only cross-reacted weakly with Samia cynthia ricini biliverdin-binding protein (BBP)-II.


Costs and problems of finding women exposed to a hazardous drug.
We recorded the costs of identifying, tracing, and contacting women who had taken diethylstilbestrol (DES) during pregnancy. Among 6,143 women who delivered a live birth between 1940 and 1960 at this medical center there were 271 who were DES exposed. An additional 271 unexposed women were selected as a comparison group for a study of the late effects of DES. The costs of locating the women were initially low but rose steeply as progressively more complicated tracing methods were used. Geographic mobility, changes in marital status, and the scanty identifying information recorded in women's medical records complicated the search and added to the costs. Tracing would be easier and less expensive if standard identifying information, including maiden name, social security number, and date of birth, were included in the medical records for all women.


Insertion of fluorescent phosphatidylserine into the plasma membrane of red blood cells. Recognition by autologous macrophages.
The interaction of macrophages with red blood cells (RBC) displaying phosphatidylserine (PS) in their surface membranes was investigated after the transfer of an exogenously supplied fluorescent lipid analog to the RBC. Nonfluorescent (quenched) lipid vesicles were formed by ultrasonication from 1-acyl-2-[(N-4-nitro-benzo-2-oxa-1,3 diazole)aminocaproyl]phosphatidyl-serine (NBD-PS) or 1-acyl-2[(N-4-nitrobenzo-2-oxa-1,3 diazole)aminocaproyl]phosphatidylcholine (NBD-PC). The interaction of these vesicles with RBC was monitored as a function of vesicle concentration by assessment of the degree to which cell-associated lipid fluorescence was dequenched after vesicle treatment. When vesicle concentrations of less than 100 ng/ml were used, lipid fluorescence was largely dequenched, indicating that lipid transfer was the predominant mechanism of both NBD-PS and NBD-PC uptake; however, when vesicle concentrations were increased to greater than 100 ng/ml, a concentration-dependent increase in the fraction of quenched cell-associated lipid was observed, indicating that another mechanism, possibly vesicle-cell adhesion, also occurred. Using NBD-PS at concentrations at which dilution of all the phospholipid analog in the recipient cell membrane could be unequivocally confirmed, we observed that the uptake of NBD-PS-treated RBC by macrophages was increased 5-fold over that of controls, whereas the uptake of RBC containing an equivalent amount of exogenously supplied NBD-PC was unaltered. Furthermore, preincubation of macrophage monolayers with vesicles containing PS resulted in a approximately 60% inhibition in the uptake of NBD-PS-treated RBC, whereas no inhibition in the uptake of control, opsonized, or NBD-PC-treated RBC was observed. These findings suggest that PS in the outer leaflet of RBC might serve as a signal for triggering their recognition by macrophages.


Calcium binding in chemically skinned fibers of rat myocardium during force development.
The amount of bound calcium and force were measured in chemically skinned rat myocardial fibers during isometric contraction at different concentrations of free Ca2+. The data obtained suggest that calcium binding by cardiac myofibrils is cooperative and probably depends on mechanical tension.


A modular ROS-responsive platform co-delivered by 10-hydroxycamptothecin and dexamethasone for cancer treatment.
Traditional and single treatment strategies are difficult to achieve good results due to tumor resistance and complex mechanisms. Combination therapy through co-delivery systems is one of the methods to improve the effectiveness of cancer treatment. The polyprodrug platform has inherent advantages such as high drug loading and strong stability. Herein, a new reactive oxygen species (ROS)-responsive micelle composed of poly 10-hydroxycamptothecin (pHCPT) and PEG is reported, which loaded dexamethasone (DEX) as synergistic drugs. The micelles collapse in the complex microenvironment of tumor cells to release DEX. The first released DEX can increase the ROS level of tumor cells, thereby facilitating the cleavage of thioketal bonds to release intact HCPT molecules. Meanwhile, DEX can normalize tumor blood vessels, reduce adverse reactions, and further improve the efficacy of HCPT. This co-delivery system shows an ideal tumor suppressive effect in vivo and in vitro. Designing drugs into a modular multi-drug platform and selecting appropriate synergistic drugs according to the treatment plan provides a convenient strategy for future clinical treatment.


Neutrophil adhesion is impaired in rat model of cholestasis.
A high incidence of septic complications has been documented in patients with obstructive jaundice undergoing surgery. Because neutrophils play a central role in the response to infection, the aim of this study was to investigate neutrophil function in a rat model of acute cholestasis induced by bile duct resection. Neutrophil function was assessed using both in vivo and in vitro techniques. The inflammatory response was defective in vivo in bile duct-resected (BDR) rats compared with sham-resected controls. Furthermore, proinflammatory stimulus-induced neutrophil adherence and emigration from mesenteric values, assessed in vivo using intravital microscopy, was attenuated in BDR vs. sham rats. Neutrophils isolated from BDR and sham rats studied in vitro adhered to a rat biological substratum similarly. However, stimulated neutrophil adherence was eliminated in the presence of BDR but not sham plasma. Similar findings were observed using plasma obtained from a patient with obstructive cholestasis. Experiments performed to further characterize this antiadhesive factor in BDR plasma suggest that the factor is probably a heat-stable glycoprotein. Cholestasis in the rat is associated with a defective acute inflammatory response that appears, at least in part, to be caused by a constituent of cholestatic plasma that is antiadhesive to neutrophils.


[Cerebellum and lower urinary tract].
To review the role of cerebellum on the lower urinary tract dynamics. Anatomic-functional methodology including structural, functional and neurotransmitters study. We describe the complex connections of the cerebellum and its influence on the lower urinary tract function. It is surprising the functional relationship between cerebellum and lower urinary tract, playing a inhibitory modulating role during the filling phase and facilitating the voiding phase.


Point of care HIV testing with oral fluid among returnee migrants in a rural area of Bangladesh.
To determine HIV prevalence and assess the acceptability of HIV testing using oral fluid as a point of care (PoC) test method among returnee migrants in a rural area of Bangladesh. A cross-sectional study. Matlab is a rural area southeast of Dhaka where icddr,b hosts a health and demographic surveillance system covering 225,826 people of whom 934 are returnee migrants. The sample size of 304 was proportionately distributed among randomly selected households. HIV antibodies in oral fluid were tested using OraQuick Rapid HIV 1/2 antibody test. To understand reasons of acceptability a short questionnaire was applied and 32 in-depth interviews were conducted. Of 304 returnee migrants approached, 97.4% accepted the test. The prevalence of HIV was 0.3% without a confirmatory blood test. Reasons for acceptance included easy accessibility of the test at the door-step which saved resources (i.e., time and money), comfortable test-procedure without any pain and fear, and receiving quick results with confidentiality. Some described knowing HIV status as a way to 'get certified' (of sexual fidelity) and to confront a prevailing silent stigma against migrants. Acceptability was moreover found to be grounded in icddr,b's institutional reputation and its close relationship with the local community. The PoC oral fluid test for HIV has shown for the first time that assessment of HIV prevalence in rural-based returnee migrants is possible. Findings also suggest that PoC oral fluid test has the potential of increasing accessibility to HIV testing as it was found to be highly acceptable.


Archaeological science, globalisation, and local agency: gold in Great Zimbabwe.
Great Zimbabwe (CE1000-1600) is world famous for outstanding cultural innovations and localised and globalised entanglement with trans-Africa and trans-Indian Ocean exchange. New excavations yielded fragments of over a hundred gold processing vessels comprising reused pottery and purpose-made crucibles from stratified contexts in the Eastern Ridge Ruins and adjacent areas. Selected samples were studied using archaeological, microscopic, and compositional (SEM-EDS) techniques. All ceramics were made of alumina-rich clays and contain minerals common to granite-derived lithologies typical of the area, although it is possible that particularly refractory clays were selected to make crucibles locally. These technical ceramics were used for refining and collecting gold at high temperature, most likely producing not only relatively standardised ingots but also finished objects. The composition of the gold prills set in crucible slag is consistent with that of natural, unalloyed gold, while the variability in silver levels and minor impurities point to heterogeneous sources of the gold. Considering these finds in their multiple site and regional contexts, and together with complementary threads of information from early reports of antiquarians and looters, we argue that local agency and gold consumption were much more significant than generally assumed. The conclusion to the paper is that Great Zimbabwe's famous participation in local and global exchanges was backed by internally driven but improvisation laden production and consumption occurring in homesteads located throughout its various settlements. We end by raising a word of caution about oversimplified narratives of globalisation and their archaeological expressions (see Supplementary Material S0 for the abstract in Shona). The online version contains supplementary material available at 10.1007/s12520-023-01811-7.


Flower-like platinum-cobalt-ruthenium alloy nanoassemblies as robust and highly efficient electrocatalyst for hydrogen evolution reaction.
Exploring hydrogen evolution reaction (HER) catalyst with highly catalytic features in alkaline conditions is considered as significance for water splitting. In this study, a general and simple method was developed to prepare flower-like platinum-cobalt-ruthenium alloy nanoassemblies (PtCoRu NAs) by using murexide and cetyltrimethylammonium chloride (CTAC) as the co-structure-directing agents. Benefiting from the structural advantages and multimetallic compositions, the as-prepared PtCoRu NAs displayed remarkably enhanced electrocatalytic performance for the HER in 1.0 M KOH, with a low overpotential (η, 22 mV) to drive 10 mA cm-2, small Tafel slope (46 mV dec-1), and high exchange current density (j0, 3.30 mA cm-2) during the long-term electrolysis. The as-developed strategy sheds some valuable guidelines for preparing advanced multimetallic catalysts for production of hydrogen in fuel cells.


Percutaneous tibial nerve stimulation maintenance therapy for overactive bladder in women: long-term success rates and adherence.
Our objectives are to (1) identify predictors of treatment success in women with overactive bladder (OAB) after 1 year of percutaneous tibial nerve stimulation (PTNS) maintenance therapy, (2) identify trends in success rates during that 1 year, and (3) assess maintenance treatment adherence. A retrospective study of 141 women with OAB was performed with the definition of success based on a Patient Global Impression-Improvement (PGI-I) score of 1 ("very much better") or 2 ("much better") or a PGI-I score of 1, 2, or 3 ("a little better"). Multivariable logistic regression was performed to identify factors associated with treatment response and the Cochrane-Armitage trend test to identify changes in the scores over time. After completing 12 weekly treatments, 141 women initiated maintenance therapy with a mean treatment interval of 29 days. At 1 year, 75/141 (53.2%) had discontinued treatment. Those adherent with treatment had a sustained treatment response, with 66.2% of women reporting a PGI-I score of 1, 2 and 92.3% reporting a PGI-I score of 1, 2, or 3 at 1 year. Considering those women who discontinued maintenance therapy as treatment failures, the success rate of 1 year of maintenance therapy ranged from 30.7%-42.9%. No clinical factors were found to be predictive of maintenance treatment success or failure. Although an effective treatment for those adherent, discontinuation rates of PTNS maintenance therapy at 1 year are high. Given the low numbers of women referred to maintenance therapy, and the high discontinuation rates, long-term PTNS treatment may be feasible for only a minority of women with OAB.


Immobilizing Surface Halide in Perovskite Solar Cells via Calix[4]pyrrole.
Halide diffusion across the charge-transporting layer followed by a reaction with metal electrode represents a critical factor limiting the long-term stability of perovskite solar cells (PSCs). In this work, a supramolecular strategy with surface anion complexation is reported for enhancing the light and thermal stability of perovskite films, as well as devices. Calix[4]pyrrole (C[4]P) is demonstrated as a unique anion-binding agent for stabilizing the structure of perovskite by anchoring surface halides, which increases the activation energy for halide migration, thus effectively suppressing the halide-metal electrode reactions. The C[4]P-stabilized perovskite films preserve their initial morphology after ageing at 85 °C or under 1 sun illumination in humid air over 50 h, significantly outperforming the control samples. This strategy radically tackles the halide outward-diffusion issue without sacrificing charge extraction. Inverted-structured PSCs based on C[4]P modified formamidinium-cesium perovskite exhibit a champion power conversion efficiency of over 23%. The lifespans of unsealed PSCs are unprecedentedly prolonged from dozens of hours to over 2000 h under operation (ISOS-L-1) and 85 °C ageing (ISOS-D-2). When subjected to a harsher protocol of ISOS-L-2 with both light and thermal stresses, the C[4]P-based PSCs maintain 87% of original efficiency after ageing for 500 h.


Two Cases of Retained Cement after Hip Hemiarthroplasty. Don't Forget the Basics.
Hemiarthroplasty as a treatment for femoral neck fractures is controversial with evolving understanding of its complications. One set of complications relates to the use of cement for these procedures. This case study presents two cases that were complicated by retained cement in the acetabulum that was identified in final intraoperative check with x-rays. In both cases, the incision was reopened and retained fragments were removed. We aim to remind the orthopaedic surgery community that this complication can occur even to the careful, experienced surgeon and to recommend the steps necessary to minimize the risk of its occurrence.


Researchers from various fields of medicine, health sciences, social sciences, cultural studies, history, literature, and education seek to develop new perspectives on medicine and the humanities, thus connecting these two fields with each other. In this interdisciplinary field of research, the so-called Medical Humanities, a wide spectrum of research approaches has emerged. Among other questions, the Medical Humanities are concerned with how literature and art provide insights into human conditions and how one can gain a better and more holistic understanding of a disease, such as dementia. Specific examples of application illustrate what the Medical Humanities can contribute to science and society.


An Evaluation of Local Implementing Partner Performance During the First 2 Years of the USAID/PEPFAR Transition.
Locally led and owned development is considered the best practice for international aid. As an implementing agency for the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the U.S. Agency for International Development (USAID) supported the goal of transitioning 70% of its portfolio funding directly to local organizations by 2020, including partner country governments. However, limited evidence or evaluation exists on how such a transition can help achieve HIV-related health outcomes. We evaluated monitoring, evaluation, and reporting performance; calculated indicators; and quality of service across the HIV/AIDS treatment cascade for local and international partners in the USAID/PEPFAR portfolio implementing similar programs during the U.S. Government fiscal years (FY) 2019 to 2020 (October 1, 2018-September 30, 2020). We compared results aggregated globally, by country, and across individual partners. Globally, local partners met a lower proportion of their treatment targets than international partners and did not meet targets for pre-exposure prophylaxis or voluntary medical male circumcision in FY2020. However, local partners exceeded targets in programs supporting orphans, vulnerable children, and key populations affected by HIV/AIDS. Local partners also had testing positivity, linkage rates, and viral load suppression that were equivalent to or higher than that of international partners. Based on available assessments, local partners displayed quality of service delivery comparable to international partners. Local partners faced challenges, including unfamiliarity with USAID funding, increasing targets across several indicators, and the syndemics of HIV/AIDS and COVID-19. A higher percentage of targets and funding led South African local partners to yield an outsized effect on global percent target achievement. While these findings should be interpreted cautiously due to limited sample size and short time horizon, they are a key first step in evaluating the local partner transition support of the long-term goal of sustained epidemic control of HIV/AIDS.


Cervical Cancer Screening Positivity Among Women Living With HIV in CDC-PEPFAR Programs 2018-2022.
The US President's Emergency Plan for AIDS Relief aims to address the higher risk of cervical cancer among women living with HIV by offering high-quality screening services in the highest burden regions of the world. We analyzed the US President's Emergency Plan for AIDS Relief Monitoring, Evaluation, and Reporting data from Centers for Disease Control and Prevention-supported sites in 13 countries in sub-Saharan Africa for women living with HIV aged older than 15 years who accessed cervical cancer screening services (mostly visual inspection, with ablative or excisional treatment offered for precancerous lesions), April 2018-March 2022. We calculated the positivity by age, country, and clinical visit type (first lifetime screen or routine rescreening). We fitted negative binomial random coefficient models of log-linear trends in time to estimate the probabilities of testing positive and any temporal trends in positivity. Among the 2.8 million completed cancer screens, 5.4% identified precancerous lesions, and 0.8% were positive for suspected invasive cervical cancers (6.1% overall). The positivity rates declined over the study period among those women screening for cervical cancer for the first time and among those women presenting to antiretroviral therapy clinics for routine rescreening. These positivity rates are lower than expectations set by the published literature. Further research is needed to determine whether these lower rates are attributable to the high level of consistent antiretroviral therapy use among these populations, and systematic program monitoring and quality assurance activities are essential to ensure women living with HIV have access to the highest possible quality prevention services.


Immiscible electrolyte systems based on asymmetric hydrophobic room temperature ionic liquids.
The effect on the melting point of the introduction of asymmetry in tetraalkylammonium halide salts has been investigated leading to the synthesis of new, hydrophobic (room temperature) ionic liquids suitable for liquid/liquid electrochemistry; one of these, tri(hexyl)decylammonium tetrakis(pentafluorophenyl)borate, displays the largest electrochemical window observed to date for a biphasic room temperature ionic liquid system.


Rare prenylated isoflavonoids from the young twigs of Millettia extensa and their cytotoxic activities.
Three new isoflavonoids, millexatins N-P (1-3), along with seven known compounds (6-10), were isolated from the acetone extract of the young twigs of Millettia extensa. The structures were characterized by NMR spectroscopic and mass spectrometric analyses. Millexatin N (1) is an unusual geminal diisoprenylated isoflavone with a modified ring A. Millexatin P (3) is an unusual isoflavone with a cyclohexyl substituent on ring B, which is extremely rare in nature. The isolated metabolites (1, 2, and 6-10) were evaluated for cytotoxicities against MDA-MB231, Huh-7, KKU-100 and normal human dermal fibroblast (NHDF) cell lines. Only compounds 1, 6 and 8 showed cytotoxicities against all cell lines with IC50 values ranging from 13.9 to 30.9 μM.


Impact of Faradaic Interlayer Confinement and Carbon-Centered Macrostructure Designs for Ion Capture and the Recovery of Elements.
Environmental protection associated with renewable energy is among the most critical challenges for translational ion-capture based on capacitive storage of ions in electrical double layers at the interface of electrode and electrolyte. Electric double-layer capacitance with charge induction and faradaic pseudo-capacitance with charge transfer classifies the capacitance of the electrochemical interface. The electrochemical interface in most energy technologies involves porous and pseudocapacitive redox materials that offer varying degrees of electrolyte confinement. In this review, we discuss the factors affecting water desalination, such as the effect of nanopores for ion capture, the ion sieving effect, the effect of hydration energy, and hydration radius in the carbon sub-nanometer pore. Moreover, the surface phenomena of electrodes, including carbon corrosion, and the potential of zero charge to control the oxidation of carbon electrodes are explained along with protection mechanisms. The various capacitive deionization (CDI) operations and the corresponding electrochemical cell technologies are briefly introduced, including the significance of double-layer charging materials with faradaic intercalation, which suffer less from co-ion expulsion. Finally, we revisit the effects of various nanoarchitectures and the construction of capacitive deionization electrodes for clean water technology.


Syntheses, crystal structure and cytotoxicity of diamine platinum(II) complexes containing maltol.
The cationic complexes (1,2-diaminoethane)(maltolato)platinum(II) ([Pt(en)(ma)]+) and (1R,2R-1,2-diaminocyclohexane)(maltolato)platinum(II) ([Pt(R,R-DACH)(ma)]+) have been prepared and the structure of [Pt(R,R-DACH)(ma)]NO3 has been determined by single crystal X-ray diffraction. The geometry of the metal in [Pt(R,R-DACH)(ma)]NO3 is essentially square planar and the maltolate ligand has a geometry similar to other chelate complexes involving this ligand. The cytotoxicities of the compounds have been assessed in the human cell lines HeLa and K562 and the IC50 values are approximately 32 microM in HeLa cells and 26 microM in K562 cells. In these cell lines the cytotoxicity of cisplatin is higher than the maltolate complexes by a factor of 2 to 3 whereas the cytotoxicity of carboplatin is lower than the maltolate complexes.


Marine polysaccharides from Gelidium pacificum Okamura and Cereus sinensis reveal prebiotic functions.
Many marine polysaccharides as prebiotics can promote host health by modulating gut microbiota. This study investigated the beneficial effects of purified marine plant-derived Gelidium pacificum Okamura polysaccharide (GPOP-1) and marine animal-derived Cereus sinensis polysaccharide (CSP-1) on normal mice by modulating gut microbiota. The composition and diversity of gut microbiota were evaluated using 16S rRNA high-throughput sequencing. The results showed that GPOP-1 and CSP-1 altered the composition of the gut microbiota and promoted the growth of beneficial bacteria. At the genus level, GPOP-1 increased the relative abundance of Bacteroides, Phascolarctobacterium, and decreased the relative abundance of Ruminococcus, Helicobacter, Allobaculum, Dorea and AF12. While CSP-1 increased the relative abundance of Coprococcus, Adlercreutzia, Roseburia, Phascolarctobacterium, and decreased the relative abundance of Bacteroides, Ruminococcus and Oscillospira. The changes in the gut microbiota may affect the body weight, immune organ index and the production of short-chain fatty acids in normal mice. Compared to the normal control group, GPOP-1 decreased average weight gain while CSP-1 increased average weight gain. Furthermore, both GPOP-1 and CSP-1 significantly increased thymus and spleen indexes and total short chain fatty acids production in mice. In summary, GPOP-1 and CSP-1 exerted prebiotic effects on normal mice.


Time to connect: bringing social context into addiction neuroscience.
Research on the neural substrates of drug reward, withdrawal and relapse has yet to be translated into significant advances in the treatment of addiction. One potential reason is that this research has not captured a common feature of human addiction: progressive social exclusion and marginalization. We propose that research aimed at understanding the neural mechanisms that link these processes to drug seeking and drug taking would help to make addiction neuroscience research more clinically relevant.


How should prospective research be designed to legitimately assess the value of urodynamic studies in female urinary incontinence?
Since formal evidence demonstrating the value of urodynamic studies (UDS) in functional urology remains elusive, we aimed to consider how best to design robust research for this purpose in female urinary incontinence. An expert group was convened to debate the following considerations: (a) precedents for formally proving the value of a gold standard diagnostic test, (b) key research principles, (c) defining a study population, (d) selecting endpoints, (e) defining interventional and controls arms, (f) blinding, (g) powering the study, and (h) duration of follow-up. In each case, we considered the strengths and weaknesses of different approaches in terms of scientific validity, ethical acceptability, practicality, and likelihood of bias. We agreed that unlike evaluating therapies, attempting to judge the value of a diagnostic test based on eventual treatment success is conceptually flawed. Nonetheless, we explored the design of a hypothetical randomized controlled trial for this purpose, agreeing that: (1) the study population must sufficiently reflect its real-world counterpart; (2) clinical endpoints should include not only continence status but also other lower urinary tract symptoms and risks of management; (3) participants in the interventional arm should receive individualized management based on their UDS findings; (4) the most scientifically valid approach to the control arm-empiric treatment-is ethically problematic; (5) sufficient statistical power is imperative; and (6) ≥ 2 years' follow-up is needed to assess the long-term impact of management. Although a perfect protocol does not exist, we recommend careful consideration of our observations when reflecting on past studies or planning new prospective research.


Sequential treatment of SH-SY5Y cells with retinoic acid and brain-derived neurotrophic factor gives rise to fully differentiated, neurotrophic factor-dependent, human neuron-like cells.
A rapid and simple procedure is presented to obtain nearly pure populations of human neuron-like cells from the SH-SY5Y neuroblastoma cell line. Sequential exposure of SH-SY5Y cells to retinoic acid and brain-derived neurotrophic factor in serum-free medium yields homogeneous populations of cells with neuronal morphology, avoiding the presence of other neural crest derivatives that would normally arise from those cells. Cells are withdrawn from the cell cycle, as shown by 5-bromo-2'-deoxyuridine uptake and retinoblastoma hypophosphorylation. Cell survival is dependent on the continuous presence of brain-derived neurotrophic factor, and removal of this neurotrophin causes apoptotic cell death accompanied by an attempt to reenter the cell cycle. Differentiated cells express neuronal markers, including neurofilaments, neuron-specific enolase, and growth-associated protein-43 as well as neuronal polarity markers such as tau and microtubule-associated protein 2. Moreover, differentiated cultures do not contain glial cells, as could be evidenced after the negative staining for glial fibrillary acidic protein. In conclusion, the protocol presented herein yields homogeneous populations of human neuronal differentiated cells that present many of the characteristics of primary cultures of neurons. This model may be useful to perform large-scale biochemical and molecular studies due to its susceptibility to genetic manipulation and the availability of an unlimited amount of cells.


Adrenal Tumors in Adults.
Although most adrenal tumors are not diagnostic dilemmas, there are cases that are challenging. This may be due to the tissue provided, for example fragmented tissue received in the setting of morcellation, or it may be due to inherently challenging histology, such as in cases with equivocal features of malignancy. Additionally, much has been learned about the molecular alterations of adrenal tumors, especially pheochromocytomas. Many of these alterations represent germline mutations with significant clinical implications for patients and their families. The aim of this review is to provide an overview of the most common adrenal tumors in adults so that pathologists can tackle these interesting tumors.


Draft genome sequences of the Pseudomonas fluorescens biocontrol strains Wayne1R and Wood1R.
Pseudomonas fluorescens strains Wayne1R and Wood1R have proven capacities to improve plant health. Here we report the draft genome sequences and automatic annotations of both strains. Genome comparisons reveal similarities with P. fluorescens strain Pf-5, reveal the novelty of Wood1R, and indicate some genes that may be related to biocontrol.


Initial stay times for uncompensable occupational heat stress in young and older men: a preliminary assessment.
During uncompensable occupational heat stress, heat-mitigation controls are required to prevent core temperature exceeding recommended limits (≥38 °C). However, the initial stay time before employing controls remained unknown. We estimated these times for moderate-intensity work at 26, 28, 30, and 32 °C wet-bulb globe temperatures (WBGT) in 50 young (18-30 years) and older (50-70 years), non-heat acclimatized men. Initial stay time was 111 min at 26 °C WBGT and declined exponentially to 44 min at 32 °C WBGT. Novelty: We provide estimates of the moderate-intensity work duration before heat-mitigation is required in wet-bulb globe temperatures between 26-32 °C for young and older, non-heat acclimatized men.


Plastic deformation of superionic water ices.
Due to their potential role in the peculiar geophysical properties of the ice giants Neptune and Uranus, there has been a growing interest in superionic (SI) phases of water ice. So far, however, little attention has been given to their mechanical properties, even though plastic deformation processes in the interiors of planets are known to affect long-term processes, such as plate tectonics and mantle convection. Here, using density functional theory calculations and machine learning techniques, we assess the mechanical response of high-pressure/temperature solid phases of water in terms of their ideal shear strength (ISS) and dislocation behavior. The ISS results are well described by the renormalized Frenkel model of ideal strength and indicate that the SI ices are expected to be highly ductile. This is further supported by deep neural network molecular dynamics simulations for the behavior of lattice dislocations for the SI face-centered cubic (fcc) phase. Dislocation velocity data indicate effective shear viscosities that are orders of magnitude smaller than that of Earth's lower mantle, suggesting that the plastic flow of the internal icy layers in Neptune and Uranus may be significantly faster than previously foreseen.


Improved wave V resolution by dual-channel brain stem auditory evoked potential recording.
Brain stem auditory evoked potentials were recorded simultaneously from the vertex and ear contralateral to stimulation (Ac-Cz) and from the vertex and ear ipsilateral to stimulation (A1-Cz). There was clearer definition of wave V and less latency variability between trials in Ac-Cz channel recordings, resulting in enhanced wave form stability and greater reproducibility of wave I-V interpeak latencies. The clinical interpretation of dual-channel recordings is currently limited by the complexity of the auditory pathways, but the technique itself shows promise as a routine clinical procedure.


Dynamical binding of proline-rich peptides to their recognition domains.
Recognition of proline-rich sequences plays an important role for the assembly of multi-protein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that share characteristic features. For many complex systems containing proline-rich sequences, multiple binding modes have been found by theoretical and/or experimental studies. In this review, we discuss the different binding modes as well as the correlated dynamics of the peptides and their recognition domains, and some implications to their biological functions. Furthermore, we give an outlook of the systems in the context of systems biology.


The region of common allelic losses in sporadic renal cell carcinoma is bordered by the loci D3S2 and THRB.
Cytogenetic studies and DNA analysis have shown that the short arm of chromosome 3 is the region in the genome that is commonly deleted in renal cell carcinoma. By studying loss of heterozygosity in 41 matched tumor/normal kidney tissue pairs, we could delimit the commonly deleted part of 3p to the region between the loci THRB (in 3p24) and D3S2 (in 3p21). The regions on 3p suggested to be involved in the Von Hippel-Lindau syndrome and in hereditary renal cell carcinoma are both outside this smallest region of overlapping deletions. Consequently, renal cell cancer would be an illustration of the possibility that different genes cause the same type of tumor.


Production, characterisation and applicability of monoclonal antibodies to immunoglobulin of Japanese flounder (Paralichthys olivaceus).
Immunoglobulin (Ig) of Japanese flounder (Paralichthys olivaceus) was purified by a combination of salting-out and DEAE Sepharose Column chromatography. The purified immunoglobulin had an apparent molecular weight of 74 kDa (heavy chain) and 24 kDa (light chain) in SDS-PAGE. Eighteen hybridomas secreting monoclonal antibodies (MAbs) against Japanese flounder Ig were obtained by immunisation of Balb/C mice with purified Ig preparations, which were selected on the basis of the double indirect enzyme-linked immunosorbent assay (D-ELISA). Two of them designated as 2D8 and 2H1 were cloned by limiting dilution and characterised with western blotting, indirect immunofluorescence assay test (IIFAT) and fluorescence-activated cell sorter (FACS) analysis. Under reducing conditions in western blotting, both MAb 2D8 and MAb 2H1 were specific for the heavy chain of Japanese flounder Ig. MAb 2D8 was used to identify surface Ig-positive lymphocytes in the peripheral blood, spleen and pronephros of healthy Japanese flounder by flow cytometry. FACS analysis revealed that 40.48% of lymphocytes in the peripheral blood, 17.32% in the spleen and 9.67% in the pronephros were reactive to 2D8.


Transition metal-catalysed molecular n-doping of organic semiconductors.
Chemical doping is a key process for investigating charge transport in organic semiconductors and improving certain (opto)electronic devices1-9. N(electron)-doping is fundamentally more challenging than p(hole)-doping and typically achieves a very low doping efficiency (η) of less than 10%1,10. An efficient molecular n-dopant should simultaneously exhibit a high reducing power and air stability for broad applicability1,5,6,9,11, which is very challenging. Here we show a general concept of catalysed n-doping of organic semiconductors using air-stable precursor-type molecular dopants. Incorporation of a transition metal (for example, Pt, Au, Pd) as vapour-deposited nanoparticles or solution-processable organometallic complexes (for example, Pd2(dba)3) catalyses the reaction, as assessed by experimental and theoretical evidence, enabling greatly increased η in a much shorter doping time and high electrical conductivities (above 100 S cm-1; ref. 12). This methodology has technological implications for realizing improved semiconductor devices and offers a broad exploration space of ternary systems comprising catalysts, molecular dopants and semiconductors, thus opening new opportunities in n-doping research and applications12, 13.


Firpronil induced spermotoxicity is associated with oxidative stress, DNA damage and apoptosis in male rats.
The present study is the first to investigate and characterize the fipronil (FPN) induced spermotoxicity in male rats. Male rats were orally given FPN (2.5, 5.0 and 10 mg/kg/day) for 4 weeks. Epididymal sperms were collected and remaining testis was processed for histopathological evaluation. FPN treatment significantly reduced sperm density, motility, viability and per cent intact acrosome along with concomitant increase in spermatozoa abnormalities. Exposure of FPN caused excessive ROS generation, lipid peroxidation and alteration in mitochondrial membrane potential leading to apoptosis of spermatozoa in dose dependent manner. Higher FPN doses (5 and 10 mg/kg) markedly reduced the DNA integrity of spermatozoa. These data suggest that FPN causes male reproductive toxicity through oxidative stress induced DNA damage and apoptosis of spermatozoa.


Development of Potentiometric Sensors for C₂H₄ Detection.
Gas exhaust emissions in vehicles are increasingly restrictive in EU and USA. Diesel engines are particularly affected by limitation in hydrocarbons and NOx concentrations. This work presents a screening of working electrode materials to develop a potentiometric sensor, with the most promising material to detect being C₂H₄ at 550 °C. The device consists of a dense 8YSZ (8 mol% Y₂O₃ stabilized ZrO₂) disk as oxide-ion conducting electrolyte, whereas platinum is screen-printed in the back face as reference electrode. As working electrode, several materials such as Fe0.7Cr1.3O₃, ZnCr₂O₄, Fe₂NiO₄, La0.8Sr0.2CrO3-δ (LSC), La0.8Sr0.2MnO₃ (LSM), and NiO+5%wt Au were tested to detect C₂H₄. Sensor voltage was measured for several concentrations of C₂H₄ and CO as these are two of the major oxidizable compounds in a diesel exhaust gas. Fe0.7Cr1.3O₃ was selected as the most promising material because of its response to C₂H₄ and CO. Not only is the response to the individual analytes important, but the C₂H₄ cross-sensitivity toward CO is also important. Fe0.7Cr1.3O₃ showed a good performance to C₂H₄, with low cross-sensitivity to CO. In addition, when 0.16 ppm of phenanthrene is added, the sensor still has a slightly better response to C₂H₄ than to CO. Nevertheless, the sensor exposure to high concentrations (>85 ppm) of polycyclic aromatic hydrocarbons led to signal saturation. On the other hand, the operation in wet conditions induces lower sensor sensitivity to C₂H₄ and higher cross-sensitivity toward CO increase, i.e., the sensor response becomes similar for C₂H₄ and CO.


Efficacy of Saccharomyces boulardii for treatment of horses with acute enterocolitis.
To evaluate the viability of Saccharomyces boulardii after PO administration in clinically normal horses and its efficacy as a treatment for horses with acute enterocolitis. Prospective study. 5 clinically normal horses and 14 horses with acute enterocolitis. Feces were collected from 5 clinically normal horses and submitted for microbial culture for 2 days prior to administration of a lyophilized form of S. boulardii (25 or 50 g, PO, q 12 h) for 10 days. Feces were collected for microbial culture 5 and 10 days after treament initiation and 10 days after treatment was discontinued. Fourteen horses with acute enterocolitis were randomly allocated to receive a placebo or S. boulardii (25 g), PO, every 12 hours for 14 days. S. boulardii was not detected in feces of clinically normal horses. After administration, yeast survived within the gastroinestinal tract but did not permanently colonize it. In horses with acute enterocolitis, the severity and duration of gastrointestinal tract disease during hospitalization were significantly decreased in horses receiving S. boulardii, compared with horses receiving the placebo. Administration of S. boulardii may help decrease the severity and duration of clinical signs in horses with acute enterocolitis.


Expression, characterization and serological reactivity of a 41 kDa excreted-secreted antigen (ESA) from Toxoplasma gondii.
A Toxoplasma gondii tachyzoite expression library was screened with immune sera from T. gondii infected patients. Among others, one gene product reacted strongly with human sera and was further investigated. The gene called B10 was shown to encode a 41 kDa antigen. The complete genomic nucleotide sequence of the B10 protein has been analysed and was shown to contain one intron with conserved splice junctions. Southern blot analysis indicated that B10 is a single-copy gene. The corresponding 1.5 kb cDNA encodes a 318 amino acid sequence of mainly hydrophilic character with a putative signal sequence of 19 amino acids and no further trans-membrane domain. Immunofluorescence assays and immunoblots with a preparation of excreted-secreted antigens (ESA) suggested that the native protein is secreted into the parasitophorous vacuole and its delimiting membrane, indicating that B10 is a member of the ESA family of T. gondii. Recombinant B10 protein exhibited a strong reactivity with human serum samples both in ELISA and in immunoblots.


Epidemiology (1980-1985) and nonspecific prophylaxis of Q fever in the USSR (survey).
A review of the epidemiology and nonspecific prophylaxis of Q fever in the USSR during 1980-1985 is presented. Attention is paid of the source to infection, the seroprevalence of antibodies to Coxiella burnetii in man and livestock and the possibilities of prophylaxis against Q fever under conditions of mandatory registration of this disease.


Effectiveness and Treatment Compliance of Salmeterol-Fluticasone Easyhaler® Among Patients with Asthma, COPD, or Asthma-COPD Overlap Syndrome: Real-World Study Findings.
For inhalation therapies to be effective, it is crucial that patients manage inhaler use correctly in their everyday life and achieve treatment compliance. We investigated the effectiveness of the salmeterol-fluticasone propionate Easyhaler® (SF EH) device-metered dry powder inhaler in a real-world setting in Hungary among adult patients with asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap syndrome (ACO). A prospective, open-label, multicenter, noninterventional, investigator-sponsored study was conducted in outpatient pneumonology centers. Eligible patients were aged ≥ 18 years with either a new diagnosis of asthma, COPD, or ACO, or whose disease was not controlled with preexisting medication. Data were collected at baseline and 12 + 4 weeks, including the asthma control test (ACT), COPD assessment test (CAT), spirometry parameters [including forced expiratory volume for 1 s (FEV1)], and physician- and patient-reported outcomes. Five hundred sixteen patients were recruited from 103 centers: 376 with asthma; 104 with COPD; and 36 with ACO. At week 12, there were significant improvements from baseline in both mean ACT score in patients with asthma (14.4 ± 4.2 versus 21.4 ± 2.8; P < 0.001) and mean CAT score in patients with COPD (24.0 ± 6.1 versus 16.0 ± 5.8; P < 0.001). Significant improvement was observed when the switch from the most frequently used previous inhalers was analyzed separately. Mean FEV1 improved from 76.0% ± 17.2 to 84.7% ± 16.1 (P < 0.001) and from 53.8% ± 15.0 to 59.9% ± 15.0 (P < 0.001) in patients with asthma or COPD, respectively. The study demonstrated improved physician-rated overall treatment compliance and patient preference for the SF EH over 3 months use compared with previous inhaler treatment, with patients effectively adopting the SF EH into everyday life. Treatment with SF EH significantly improved patients' lung function parameters and disease control.


The use of dexmedetomidine as an adjuvant to benzodiazepine-based therapy to decrease the severity of delirium in alcohol withdrawal in adult intensive care unit patients: a systematic review.
Chronic alcohol consumption is a prevalent issue. Healthcare professionals often discover their patient has an alcohol consumption issue when they are admitted to the hospital and no longer have access to alcohol. The global standard for treating alcohol withdrawal syndrome (AWS) symptoms are benzodiazepines; however this therapy is often inadequate to control symptoms of delirium in adult intensive care unit (ICU) patients due to an imbalance of inhibitory and excitatory neurotransmitters. The objective of the systematic review is to examine the clinical effectiveness of dexmedetomidine as an adjuvant to benzodiazepine-based therapy versus benzodiazepine-based therapy alone in decreasing the severity of delirium associated with AWS in adult ICU patients. This review considered studies that included adult ICU patients over the age of 18 who were experiencing delirium associated with alcohol withdrawal. Patients admitted to the ICU with the diagnosis of AWS were included in the study.This review considered studies that evaluated dexmedetomidine as an adjuvant therapy to benzodiazepine-based therapy, compared to the use of benzodiazepine-based therapy alone in ICU patients experiencing alcohol withdrawal delirium.This review considered randomized controlled trials, non-randomized controlled trials, quasi-experimental, before and after studies, prospective and retrospective cohort studies, case control studies, analytical cross sectional studies, case series, individual case reports and descriptive cross sectional studies for inclusion.The systematic review evaluated dexmedetomidine as an adjuvant to benzodiazepine-based therapy to decrease delirium severity in alcohol withdrawal in ICU patients. The general outcome of delirium severity was measured using the Clinical Institute Withdrawal Assessment Score - Revised (CIWA), the Ramsey scale, the Richmond Agitation Sedation Score (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). The search strategy aimed to find both published and unpublished studies. A three-step search strategy was utilized in this review and included English language studies published after 1997. A search of Ovid/MEDLINE, EMBASE, Cochrane, Joanna Briggs Institute and nine other databases was conducted. Two independent reviewers using the Joanna Briggs Institute's standardized appraisal tool critically appraised the studies. A third independent reviewer was available to appraise studies if the two original reviewers disagreed in their assessments. There were no disagreements in findings between the two independent reviewers. Data was extracted using the standardized Joanna Briggs Institute's data extraction instruments. Statistical pooling was done using meta-analysis and findings are presented using a forest plot and narrative form. Four studies were included in the review, three retrospective case series and one prospective case series with a total sample size of 55 patients. Three studies used the CIWA score as the outcome measure and one study used the RASS score as the outcome measure. A meta-analysis of the three studies using the CIWA demonstrated that adjuvant use of dexmedetomidine with benzodiazepine-based therapy decreased CIWA scores (Weighted Mean Difference [WMD] -5.2, 95% Confidence Interval [CI] -6.24 to -4.16, p <0.0001). The final study using RASS scores reported improvement with adjuvant treatment with dexmedetomidine compared to benzodiazepine-based therapy alone. The use of dexmedetomidine as an adjuvant to benzodiazepine-based therapy decreased delirium more effectively than benzodiazepine-based therapy alone in adult ICU patients experiencing alcohol withdrawal delirium as evidenced by a decrease in CIWA and RASS scores. In adult ICU patients who are experiencing alcohol withdrawal delirium that is not controlled with benzodiazepine-based therapy alone, healthcare providers should consider dexmedetomidine as an adjuvant to standard benzodiazepine-based therapy. The use of dexmedetomidine in the management of delirium associated with alcohol withdrawal in adult ICU patients should be further studied via large scale randomized controlled trials.


Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Antiresorptive Drugs: Proportion of Treatment Effect Explained.
Few analyses of antiresorptive (AR) treatment trials relate short-term changes in bone turnover markers (BTMs) to subsequent fracture reduction seeking to estimate the proportion of treatment effect explained (PTE) by BTMs. Pooling such information would be useful to assess new ARs or novel dosing regimens. In the Foundation for the National Institutes of Health (FNIH) Bone Quality project, we analyzed individual-level data from up to 62,000 participants enrolled in 12 bisphosphonate (BP) and four selective estrogen receptor modulator (SERM) placebo-controlled fracture endpoint trials. Using BTM results for two bone formation markers (bone-specific alkaline phosphatase [bone ALP] and pro-collagen I N-propeptide [PINP]) and one bone resorption marker (C-terminal telopeptide of type I collagen [CTX]) and incident fracture outcome data, we estimated the PTE using two different models. Separate analyses were performed for incident morphometric vertebral, nonvertebral, and hip fractures over 1 to 5 years of follow-up. For vertebral fracture, the results showed that changes in all three BTMs at 6 months explained a large proportion of the treatment effect of ARs (57 to >100%), but not for and non-vertebral or hip fracture. We conclude that short-term AR treatment-related changes in bone ALP, PINP, and CTX account for a large proportion of the treatment effect for vertebral fracture. Change in BTMs is a useful surrogate marker to study the anti-fracture efficacy of new AR compounds or novel dosing regiments with approved AR drugs. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.


[Effect produced by the alkaloid fraction of Mimosa tenuiflora (tepescohuite) on the peristaltic reflex of the guinea pig ileum].
An alkaloidal fraction was obtained from Mimosa tenuiflora (Willd.) Poir (tepescohuite) trunk bark. The product contained mainly an indolealkylamine and three minor alkaloids. This fraction inhibited the peristaltic reflex in the guinea-pig isolated ileum in vitro.


Gastric aspirate shake test for diagnosis of surfactant deficiency in neonates with respiratory distress.
The gastric aspirate shake test (GST) was evaluated in 77 newborns with respiratory distress for predicting hyaline membrane disease (HMD) at KEM Hospital, Pune, India. Over 0.5 ml of gastric fluid was obtained within 30 min of birth and mixed with an equal volume of normal saline for 10 sec; 1 ml of 95% ethanol was then added and the mixture agitated for 10 sec. After standing for 15 min, the air-liquid interface was examined for bubbles. All 21 infants with a negative GST developed HMD. However, 12 infants with an intermediate and nine with a positive test also developed HMD. None of the infants with other respiratory disorders, e.g. transient tachypnoea and pneumonia, had a negative GST. A negative GST had a specificity of 100%, sensitivity of 70% and positive predictive value of 100% for developing HMD. GST is a useful test for predicting HMD and might be of particular value in developing countries.


Immune cell and transcriptomic analysis of the human decidua in term and preterm parturition.
Is labour, both at term and preterm, associated with alterations in decidual lymphocyte densities and widespread changes to the decidual transcriptome? The onset of parturition, both at term and preterm, is associated with widespread gene expression changes in the decidua, many of which are related to inflammatory signalling, but is not associated with changes in the number of any of the decidual lymphocyte populations examined. Given its location, directly at the maternal-foetal interface, the decidua is likely to play a pivotal role in the onset of parturition, however, the molecular events occurring in the decidua in association with the onset of labour, both at term and preterm, remain relatively poorly defined. Using flow cytometry and microarray analysis, the present study aimed to investigate changes to the immune cell milieu of the decidua in association with the onset of parturition and define the decidual gene signature associated with term and preterm labour (PTL). This study used decidual samples collected from 36 women across four clinical groups: term (38-42 weeks of gestation) not in labour, TNL; term in labour, TL; preterm (<35 weeks of gestation)not in labour, PTNL; and preterm in labour, PTL. Decidual lymphocytes were isolated from fresh decidual tissue collected from women in each of our four patient groups and stained with a panel of antibodies (CD45, CD3, CD19, CD56, CD4, CD8 and TCRVα24-Jα18) to investigate lymphocyte populations present in the decidua (TNL, n = 8; TL, n = 7; PTNL, n = 5; PTL, n = 5). RNA was extracted from decidual tissue and subjected to Illumina HT-12v4.0 BeadChip expression microarrays (TNL, n = 11; TL, n = 8; PTNL, n = 7; PTL, n = 10). Quantitative real-time PCR (qRT-PCR) was used to validate the microarray results. The relative proportions of decidual lymphocytes (T cells, NK cells, B cells and invariant natural killer (iNKT) cells) were unaffected by either gestation or labour status. However, we found elevated expression of the non-classical MHC-protein, CD1D, in PTL decidua samples (P < 0.05), suggesting the potential for increased activation of decidual invariant NKT (iNKT) cells in PTL. Both term and PTL were associated with widespread gene expression changes, particularly related to inflammatory signalling. Up-regulation of candidate genes in TL (IL-6, PTGS2, ATF3, IER3 and TNFAIP3) and PTL (CXCL8, MARCO, LILRA3 and PLAU) were confirmed by qRT-PCR analysis. Microarray data are available at www.ebi.ac.uk/arrayexpress under accession number E-MTAB-5353. Whilst no changes in lymphocyte number were observed across our patient samples, we did not investigate the activation state of any of the immune cell sub-populations examined, therefore, it is possible that the function of these cells may be altered in association with labour onset. Additionally, the results of our transcriptomic analyses are descriptive and at this stage, we cannot prove direct causal link with the up-regulation of any of the genes examined and the onset of either term or PTL. Our findings demonstrate that the onset of parturition is associated with widespread changes to the decidual transcriptome, and there are distinct gene expression changes associated with term and PTL. We confirmed that an inflammatory signature is present within the decidua, and we also report the up-regulation of several genes involved in regulating the inflammatory response. The identification of genes involved in regulating the inflammatory response may provide novel molecular targets for the development of new, more effective therapies for the prevention of preterm birth (PTB). Such targets are urgently required. This work was supported by Medical Research Council (grant number MR/L002657/1) and Tommy's, the baby charity. Jane Norman has had research grants from the charity Tommy's and from the National Institute for Health Research on PTB during the lifetime of this project. Jane Norman also sits on a data monitoring committee for GSK for a study on PTB prevention and her institution receives financial recompense for this. The other authors do not have any conflicts of interest to declare.


Spatial distribution of polycyclic aromatic hydrocarbons in the water-sediment system near chemical industry parks in the Yangtze River Delta, China.
The Yangtze River Delta (YRD) is one of the most populated and economically prosperous regions in China and contains numerous chemical industry parks. To understand the distribution and sources of polycyclic aromatic hydrocarbons (PAHs), surface water and sediment samples were collected from areas around the industrial parks. The total concentrations of 19 PAHs in water and sediment were 32.98-286 ng L-1 and 15.14-5355 ng g-1, respectively. The highest PAH concentrations in water and sediment were found in samples from Wuxi city, which were dominated by high molecular weight (HMW) PAHs, and strongly influenced by fine chemical parks. HMW compounds dominated in the sediment with PAHs containing four and five rings accounting for 61% of the sedimentary ΣPAHs, PAHs in water were dominated by low molecular weight (LMW) compounds (PAHs with two and three rings represented >68% of ΣPAHs). The results of isomeric ratio analysis and principal component analysis with multiple linear regression indicated that the PAH concentrations in water and sediment near the YRD chemical parks are strongly influenced by industrial emissions. The fugacity fraction approach was applied to explain the trend for water-sediment exchange of 16 priority PAHs, which showed that net fluxes for most were from the sediment into water. The results indicated that the LMW PAHs were in a non-steady state in the sediment-water system. An ecological risk assessment showed that most sites were low to medium risk, but one site was high risk.


Microsatellites in immune-relevant regions and their associations with Maedi-Visna and ovine pulmonary adenocarcinoma viral diseases.
Maedi-Visna (MV) and ovine pulmonary adenocarcinoma (OPA) are two retroviral diseases occurring worldwide that affect adult sheep. Differences in incidence, which may be related to sheep-rearing and housing choices, as well as to genetics, and disease progression have been reported for both diseases. In this work four microsatellites located in immune-relevant regions, the major histocompatibility complex (MHC) region, interferon-γ and interleukin-12p35, were genotyped to determine their association with disease progression. The analysed sample included Latxa sheep with and without OPA and MV-characteristic lesions in their lungs. The microsatellites in the MHC were the most diverse, while the ones located in the cytokines were the less polymorphic. In the case of IFN-γ the results suggested the presence of null alleles. Significant results were detected for several microsatellite alleles in the association analysis carried out by logistic regression. All statistical analyses included a flock effect adjustment to avoid false positives due to genetic structuration. MHC Class I microsatellite alleles OMHC1*205 and OMHC1*193 were associated with disease progression for Maedi and OPA, respectively. Moreover, MHC Class II microsatellite allele DRB2*275 was associated with presence of lesions in Maedi. Furthermore, the MHC microsatellites were combined for a bioinformatic haplotype inference with the PHASE software. In total, 73 haplotypes were detected, 18 of them in more than 6 animals. After standard and weighted logistic regression analysis, two of them were significantly associated with susceptibility: OMHC1*205-DRB2*271 for Maedi and OMHC1*193-DRB2*271 for OPA, both with the Class I microsatellite alleles associated in the marker by marker study. Although more extensive analyses are needed to disentangle the relationship between host genetics and disease, as far as we know this is the first study demonstrating a significant association between sheep MHC Class I microsatellite alleles and susceptibility to Maedi-Visna and OPA viral diseases.


Amorphous silicon and amorphous silicon nitride films prepared by a plasma-enhanced chemical vapor deposition process as optical coating materials.
Durable, uniform, and reproducible amorphous silicon and amorphous silicon nitride thin films deposited by plasma-enhanced chemical vapor deposition that are appropriate for the design and fabrication of optical interference filters in the near-infrared region are found. Optical and physicalk properties of single-layer films are discussed. The durability and performance of Fabry-Perot interference filters and a 15-layer long-pass edge filter in the near-infrared region designed and fabricated with these two thin-film materials are also reported.


Water channel activities of Mimosa pudica plasma membrane intrinsic proteins are regulated by direct interaction and phosphorylation.
cDNAs encoding aquaporins PIP1;1, PIP2;1, and TIP1;1 were isolated from Mimosa pudica (Mp) cDNA library. MpPIP1;1 exhibited no water channel activity; however, it facilitated the water channel activity of MpPIP2;1 in a phosphorylation-dependent manner. Mutagenesis analysis revealed that Ser-131 of MpPIP1;1 was phosphorylated by PKA and that cooperative regulation of the water channel activity of MpPIP2;1 was regulated by phosphorylation of Ser-131 of MpPIP1;1. Immunoprecipitation analysis revealed that MpPIP1;1 binds directly to MpPIP2;1 in a phosphorylation-independent manner, suggesting that phosphorylation of Ser-131 of MpPIP1;1 is involved in regulation of the structure of the channel complex with MpMIP2;1 and thereby affects water channel activity.


Cysteamine induced-duodenal ulcers are associated with a selective depletion in gastric and duodenal calcitonin gene-related peptide-like immunoreactivity in rats.
We have measured the endogenous levels of gastric and duodenal calcitonin gene-related peptide (CGRP)-, neurokinin A (NKA)-, galanin-vasoactive intestinal polypeptide (VIP)- and neuropeptide Y (NPY)-like immunoreactivity (li) in relation to cysteamine-induced gastric lesions and duodenal ulcers in rats. CGRP-li but not NKA-, galanin-, VIP- or NPY-li was decreased in gastric and duodenal samples following a single ulcerogenic dose of cysteamine (900 mg/kg p.o.). Temporal relationships of this phenomenon showed that CGRP-li was selectively decreased (stomach 45%, duodenum 68% as compared to controls, respectively after 24 h) concomitantly to the formation of acute gastric lesions and duodenal ulcers. Animals bearing healed ulcers 12 days after cysteamine, had gastroduodenal CGRP-li similar to control values. Pretreatment with the selective sensory neurotoxin capsaicin decreased gastroduodenal CGRP-li but not NKA-, galanin-, VIP- or NPY-li, showing that CGRP might be considered a marker of the afferent innervation of the gastroduodenal tract. The residual gastroduodenal CGRP-li levels in capsaicin-pretreated animals were not decreased by cysteamine administration, indicating that the effect of cysteamine is restricted to a peptide pool of primary afferent origin. Duodenal CGRP-li is selectively decreased by the duodenal ulcerogen cysteamine during the acute phase of ulcers formation and might be among the local mediators which afford protection against the ulcerogenic stimuli.