Design, synthesis, and biological evaluation of highly potent small molecule-peptide conjugates as new HIV-1 fusion inhibitors.
The small molecule fusion inhibitors N-(4-carboxy-3-hydroxyphenyl)-2,5-dimethylpyrrole (NB-2) and N-(3-carboxy-4-hydroxyphenyl)-2,5-dimethylpyrrole (A12) target a hydrophobic pocket of HIV-1 gp41 and have moderate anti-HIV-1 activity. In this paper, we report the design, synthesis, and structure-activity relationship of a group of hybrid molecules in which the pocket-binding domain segment of the C34 peptide was replaced with NB-2 and A12 derivatives. In addition, the synergistic effect between the small molecule and peptide moieties was analyzed, and lead compounds with a novel scaffold were discovered. We found that either the nonpeptide or peptide part alone showed weak activity against HIV-1-mediated cell-cell fusion, but the conjugates properly generated a strong synergistic effect. Among them, conjugates Aoc-βAla-P26 and Noc-βAla-P26 exhibited a low nanomolar IC50 in the cell-cell fusion assay and effectively inhibited T20-sensitive and -resistant HIV-1 strains. Furthermore, the new molecules exhibited better stability against proteinase K digestion than T20 and C34.


Improved Value of Individual Prenatal Care for the Interdisciplinary Team.
Innovative models of prenatal care are needed to improve pregnancy outcomes and lower the cost of care. We sought to increase the value of traditional prenatal care by using a new model (PodCare) featuring a standardized visit schedule and coordination of care within small interdisciplinary teams in an academic setting. Prenatal providers and clinic staff were divided into four "Pods". Testing and counseling topics were assigned to visits based on gestational age. Interdisciplinary weekly Pod meetings provided coordination of care. A retrospective chart review was performed. The primary endpoints were the number of prenatal care visits and number of providers seen. After PodCare implementation, more patients choose care with the low-risk physician team (42% compared to 26%). Study subjects included 85 women in 2013 and 165 women in 2014. The median number of visits decreased from 13 to 10 (p < 0.00004) and the median number of providers seen decreased from 7 to 5 (p < 0.0000008). PodCare increased the value of individual prenatal care by decreasing the number of visits, increasing continuity, and providing care coordination. The model provides a robust experience in interdisciplinary care. The PodCare model may be successful at other academic institutions.


A transcriptional roadmap to the senescence and differentiation of human oral keratinocytes.
Human epithelial cells undergo morphological and molecular changes leading to terminal differentiation and replicative senescence after a finite number of cell divisions during serial subculture. However, the target genes and their functional significance in the senescence and differentiation in normal human oral keratinocytes have been poorly defined. Here, we demonstrated normal human oral keratinocytes transcriptional signature profiling to senescence and differentiation. Using microarray analysis, our findings indicated that the gene expression profiles induced by serial subculture are distinct classes of gene. The greatest number of these altered genes was identified as being related to biological pathways of transport, cell proliferation, cell cycle, defense and immune response, cell death, transcription, apoptosis, and inflammatory response, suggesting that the serial subculture is able to induce a multitude of specific gene expression changes during senescence and differentiation. Several highly upregulated genes (IL-1β, S100A8, S100A9, MMP1, MMP9, IL-8, BHLHB2, HES1, and TWIST1) in response to the serial subculture in normal human oral keratinocytes were observed. In vitro and in vivo studies also exhibited a close relationship between senescence and differentiation of primary oral keratinocytes and expression of inflammatory molecules. These results suggest a new approach to determine the biological events underlying the pathogenesis of oral keratinocyte aging.


Induced radioactivities in concrete constituents irradiated by high-energy particles.
The powdered concrete constituents of magnetite ore, pyrites ore, marble, gravel and Portland cement were prepared and irradiated by 12- GeV protons and secondary particles at the slow extracted beam line of the National Laboratory for High Energy Physics ( KEK ) 12- GeV proton synchrotron. The saturated activities for individual nuclides produced were calculated, and the time variation of photon exposure rate due to the residual activities was also evaluated for each sample. The exposure rates ranked in the following order: magnetite ore greater than pyrites ore greater than gravel greater than or equal to cement greater than marble. The levels of photon exposure rates from heavy, ordinary and marble concretes were also estimated on the basis of the results obtained for each constituent. It is suggested that the use of marble concrete in the inside wall of accelerator tunnels can reduce considerably the exposure to the accelerator maintenance workers, compared with heavy and ordinary concretes commonly used.


Sexual dysfunction after spinal cord injury.
Treatment of sexual dysfunction is an integral part of the rehabilitation of the patient with spinal cord injury. The degree of sexual dysfunction varies with the level and completeness of injury. A multidisciplinary approach is necessary to evaluate and treat these patients. Intracorporeal injections of vasoactive medications or vacuum devices are effective means of restoring erections in selected patients with spinal cord injury. Penile prostheses are rarely indicated for this purpose.


Parasite assemblages in the Western whip snake Hierophis viridiflavus carbonarius (Colubridae) from southern Italy.
Parasite assemblages of the Western whip snake Hierophis viridiflavus carbonarius were investigated from the Calabria region in southern Italy. A total of 14 parasite taxa including 6 nematodes, 3 acanthocephalans, 2 cestodes, 2 digeneans and a single pentastomid was identified. Within the study area, H. v. carbonarius serves as the final host for seven species of helminths, of which only four (Hexametra quadricornis, Kalicephalus viperae, Paracapillaria sonsinoi and Renifer aniarum) can be considered as snake specialists, while one (Oswaldocruzia filiformis) is shared with other reptiles and amphibians, and two (Paradistomum mutabile and Rhabdias fuscovenosa) with lizards. A large proportion of larval forms of six helminth taxa (about 95% of all helminths collected) was found, for which H. v. carbonarius serves as an intermediate and/or paratenic host; however, adult stages of helminths were prevalent in snakes with snout-to-vent length greater than 70 cm. Our results suggest that ontogenetic and ecological factors should exert a strong influence upon the helminth assemblage of Western whip snakes. We concluded that H. v. carbonarius plays an important role in southern Italy as an intermediate/paratenic host for species of helminths infecting vertebrate groups which may include this snake species within their feeding chain. Eleven taxa, including three potential agents of zoonosis, were added to the poorly known parasite fauna of this host.


Don't think the recovery auditors will disappear.
Medicare's Recovery Audit program is under scrutiny from all fronts, but the program is so successful, it's not going to go away, so hospitals need to continue to prepare. Make sure that documentation in the medical record shows that the services provided are medically necessary and reflects the severity of illness and intensity of service. Analyze all your denials and appeal those you think are unjustified, all the way to the administrative law judge level, if necessary. Follow screening criteria for patients with targeted diagnoses and make sure physicians are not overusing observation services.


Comparison of copper imine and amine podates: geometric consequences of podand size and donor type.
The imine podands tris[(2-nitrobenzylidene)aminoethyl]amine and tris[(2-nitrobenzylidene)aminopropyl]amine both stabilize copper(I), forming {tris[(2-nitrobenzylidene)aminoethyl]amine-kappa4N}copper(I) perchlorate acetonitrile disolvate, [Cu(C27H27N7O6)]ClO4.2CH3CN, (II), and {tris[(2-nitrobenzylidene)aminopropyl]amine-kappa4N}copper(I) perchlorate, [Cu(C30H33N7O6)]ClO4, (VI), respectively. The larger propyl-based ligand is a poorer fit for the CuI ion. The reduced amine podand tris[(2-nitrobenzyl)aminoethyl]amine binds CuII and the resulting compound, chloro{tris[(2-nitrobenzyl)aminoethyl]amine-kappa4N}copper(II) chloride ethanol solvate, [Cu(C27H33N7O6)Cl]Cl.C2H5OH, (IV), shows both intra- and intermolecular hydrogen bonding, which gives rise to RRS or SSR conformations in the podand strands rather than the expected pseudo-threefold symmetry.


An en route capacity optimization model based on air traffic control process.
In order to resolve the imbalance of demand-capacity and airspace congestion, improve the performance of the en route air traffic management, promote the development of air traffic control automation system in the future, this paper proposes an En route air traffic control process model from the perspective of operation requirements. Taking the minimization of operation time, instantaneous density, maximum lateral displacement and air traffic controllers' workload as the optimization objectives, the commonly used air traffic control instructions such as climb and descent and speed restriction are set as constraints, the algorithm is designed based on the air traffic control scheme, and a complete air traffic control process are modeled which outputs instructions for each aircraft. Finally, the model is applied to a case study in the northwest region of China. The simulation results show that compared with the actual operation process, the total operation time is reduced by 18.6%, the variance of the lateral displacement and the vertical separation are efficiently reduced, and the en route air traffic capacity is improved. The proposed model envisages the following two innovations: (ⅰ) the whole process of air traffic controllers' command is considered in the model, especially the control scheme and different types of instructions, and (ⅱ) the en route historical trajectory data of aircraft is used to as the key parameters of the input data to efficiently yield the acceptable results of the model. By quantifying the operation requirements of air traffic control, this model can also balance the distribution of traffic flow density, reduce the utilization rate of horizontal airspace, alleviate flight conflicts on air routes, and lessen the workload of controllers.


Synergistic effects of climate and landscape change on the conservation of Amazonian lizards.
The leading causes of the worldwide decline in biodiversity are global warming, allied with natural habitat loss and fragmentation. Here, we propose an analysis of the synergistic effects of these two factors in 63 species of Amazonian lizards. We predicted that the high-climatic suitability areas of species would be significantly impacted by different deforestation scenarios and the resultant landscape structure and considered that forest-dwelling species would be especially susceptible to deforestation scenarios. We also pointed out species threatened by both drivers and suggested critical areas for their future conservation. According to our results, most species will face future reductions in suitable areas for their occurrence according to five different patterns, two of which represent significant risks for 15 species. Some of these species already deal with severe habitat loss and fragmentation of their current distribution ranges, whereas others will suffer a considerable area reduction related to future range shifts. We emphasize the importance of protected areas (PAs), especially indigenous lands, and the need to plan combined strategies involving PAs' maintenance and possible implementation of ecological corridors. Finally, we highlight eight species of thermoconformer lizards that constitute present and future conservation concerns related to the combined effects of climate change and habitat loss and that should be carefully evaluated in extinction risk assessments.


Prospective histologic examinations in patients who practice traumatic hairstyling.
Alopecia is the fifth most common dermatologic diagnosis in African-American patients. Central centrifugal cicatricial alopecia (CCCA) is the most common form of scarring alopecia in this group. This study sought to evaluate clinical and histologic findings in patients without clinical alopecia who use chemical and/or thermal straighteners to determine whether follicular damage is evidenced histologically. Eight African-American women with no clinical evidence of alopecia or scalp inflammation were included in the study. All participants had engaged in some form of traumatic hair care within the previous month. Participants submitted to clinical photography and 4-mm punch biopsy. Histologic examination was performed and the characteristics of each case recorded. There were no clinical signs of alopecia or inflammation in any patient. Histopathology showed peri-infundibular lymphocytic inflammation in all patients and mild superficial perivascular lymphocytic inflammation in three. Concentric infundibular fibrosis was observed in each hair follicle in all specimens. One sample showed additional focal peri-isthmus fibrosis. There was no evidence of complete follicular dropout, follicular epithelial thinning, or premature desquamation of inner root sheaths. The mean number of hair follicles was 4.88 per 4-mm punch. Hair cycling was consistently within normal ranges. Biopsy findings characteristic of CCCA suggest that a clinical prelude exists histologically. Further follow-up may provide a longitudinal timeframe for the potential progression, halting, or reversal of disease if hairstyling practices are, respectively, continued or discontinued. Central centrifugal cicatricial alopecia is likely to represent a common pathway of inflammation and scarring that can be instigated by traumatic hairstyling practices in genetically predisposed subjects.


Effect of lipopolysaccharide and bleeding on the expression of intestinal proteins involved in iron and haem transport.
Haem carrier protein 1 (Hcpl) is a component of the haem-iron uptake pathway in the small intestine. Using quantitative real-time PCR, we examined the expression of Hcp1 and other intestinal iron-transporting proteins in male C57BL/6 mice with experimentally altered iron homeostasis. Intestinal Hcp1 mRNA content was not significantly changed by iron overload (600 mg/kg); however, it was increased to 170 % of controls 72 h after withdrawal of 0.7 ml of blood; the same treatment increased intestinal Cybrd1 mRNA to 900 % of controls. LPS treatment (1 mg/kg, 6 h) decreased intestinal Hcp1 mRNA content to 66 % of controls and Flvcr mRNA content to 65 % of controls, while Cybrd1 mRNA, Dmt1 mRNA and Fpn1 mRNA decreased to 6 %, 43 % and 32 %, respectively. In 129SvJ mice with targeted disruption of the hemojuvelin (Hfe2) gene, which display very low expression of liver hepcidin, Cybrd1 mRNA content increased to 1040 %, Dmt1 mRNA content to 200 % and Fpn1 mRNA to 150 % when compared to wild-type mice; changes in Hcp1, Abcg2 and Flver mRNA content were only minor. Overall, these results suggest that, during inflammation, the intestinal haem-iron uptake pathway is not as strongly transcriptionally downregulated as the non-haem iron uptake pathway. A decrease in circulating hepcidin increases the expression of proteins participating in non-haem iron uptake, but has no significant effect on Hcp1 mRNA content.


Anticholinergic Load: Is there a Cognitive Cost in Early Parkinson's Disease?
We evaluated the effect of anticholinergic burden on 219 participants with incident Parkinson's disease (PD) and 99 controls at study baseline and 18 months. Anticholinergic burden for each individual was calculated and summed according to the Anticholinergic Drug Scale (ADS). Medication with anticholinergic activity was more commonly prescribed in PD compared to controls, although mean ADS scores were not significantly different. Cognitive scores did not differ in PD participants taking medications with anticholinergic activity compared to those who were not. Low overall ADS scores due to increased awareness of adverse effects of medications and brevity of follow-up are potential explanations.


para-Azaquinodimethane: A Compact Quinodimethane Variant as an Ambient Stable Building Block for High-Performance Low Band Gap Polymers.
Quinoidal structures incorporating expanded para-quinodimethane (p-QM) units have garnered great interest as functional organic electronic, optical, and magnetic materials. The direct use of the compact p-QM unit as an electronic building block, however, has been inhibited by the high reactivity conveyed by its biradical character. Herein, we introduce a stable p-QM variant, namely p-azaquinodimethane (p-AQM), that incorporates nitrogen atoms in the central ring and alkoxy substituents on the periphery to increase the stability of the quinoidal structure. The succinct synthesis from readily available precursors leads to regio- and stereospecific p-AQMs that can be readily integrated into the backbone of conjugated polymers. The quinoidal character of the p-AQM unit endows the resulting polymers with narrow band gaps and high carrier transport mobilities. The study of a series of copolymers employing different numbers of thiophene units revealed an unconventional trend in band gaps, which is distinct from the widely adopted donor-acceptor approach to tuning the band gaps of conjugated polymers. Theoretical calculations have shed light on the nature of this trend, which may provide a unique class of conjugated polymers with promising optical and electronic properties.


Time course of the blindness to response-compatible stimuli.
This article examines the time course of a deficit in identifying a stimulus sharing a compatible feature with a response that is executed in parallel ("blindness to response-compatible stimuli," J. Müsseler & B. Hommel, 1997a). In 5 experiments, participants performed a timed response, and the presentation point of time of a to-be-identified stimulus was varied in respect to response execution. A blindness effect was observed when the stimulus was presented between response cue offset and response execution. In contrast, the identification of a stimulus presented before the response cue or after response execution was not affected by stimulus-response compatibility--a finding that rules out a retention-based explanation. These results support an explanation that states that the perceptual processing of a stimulus feature is impaired as long as the shared perception-action feature code is integrated into the representation of a to-be-executed response.


Spatial signature of dose patterns associated with acute radiation-induced lung damage in lung cancer patients treated with stereotactic body radiation therapy.
Thoracic radiation therapy (RT) is often associated with lung side effects, whose etiology is still controversial. Our aim was to explore correlations between local dose in the thoracic anatomy and the radiation-induced lung damage (RILD). To this end, we designed a robust scheme for voxel-based analysis (VBA) to explore dose patterns associated with RILD in non-small-cell lung cancer (NSCLC) patients receiving stereotactic body RT (SBRT). We analyzed 106 NSCLC SBRT patients (median prescription dose: 50 Gy; range: [40-54] Gy) in 4 fractions (range: [3-5]) with clinical and dosimetric records suitable for the analysis. The incidence of acute G1 RILD (RTOG grade ⩾ 1) was 68%. Each planning CT and dose map was spatially normalized to a common anatomical reference using a B-spline inter-patient registration algorithm after masking the gross tumor volume. The tumor-subtracted dose maps were converted into biologically effective dose maps (α/β = 3 Gy). VBA was performed according to a non-parametric permutation test accounting for multiple comparison, based on a cluster analysis method. The underlying general linear model of RILD was designed to include dose maps and each non-dosimetric variable significantly correlated with RILD. The clusters of voxels with dose differences significantly correlated with RILD at a given p -level (S p ) were generated. The only non-dosimetric variable significantly correlated with RILD was the chronic obstructive pulmonary disease (p = 0.034). Patients with G1 RILD received significantly (p ⩽ 0.05) higher doses in two voxel clusters S 0.05 in the lower-left lung (14 cm3) and in an area (64 cm3) largely included within the ventricles. The applied VBA represents a powerful tool to probe the dose susceptibility of inhomogeneous organs in clinical radiobiology studies. The identified subregions with dose differences associated with G1 RILD in both the heart and lower lungs endorse a trend of previously reported hypotheses on lung toxicity radiobiology.


Conserved TCP domain of Sas-4/CPAP is essential for pericentriolar material tethering during centrosome biogenesis.
Pericentriolar material (PCM) recruitment to centrioles forms a key step in centrosome biogenesis. Deregulation of this process leads to centrosome aberrations causing disorders, one of which is autosomal recessive primary microcephaly (MCPH), a neurodevelopmental disorder where brain size is reduced. During PCM recruitment, the conserved centrosomal protein Sas-4/CPAP/MCPH6, known to play a role in centriole formation, acts as a scaffold for cytoplasmic PCM complexes to bind and then tethers them to centrioles to form functional centrosomes. To understand Sas-4's tethering role, we determined the crystal structure of its T complex protein 10 (TCP) domain displaying a solvent-exposed single-layer of β-sheets fold. This unique feature of the TCP domain suggests that it could provide an "extended surface-like" platform to tether the Sas-4-PCM scaffold to a centriole. Functional studies in Drosophila, human cells, and human induced pluripotent stem cell-derived neural progenitor cells were used to test this hypothesis, where point mutations within the 9-10th β-strands (β9-10 mutants including a MCPH-associated mutation) perturbed PCM tethering while allowing Sas-4/CPAP to scaffold cytoplasmic PCM complexes. Specifically, the Sas-4 β9-10 mutants displayed perturbed interactions with Ana2, a centrosome duplication factor, and Bld-10, a centriole microtubule-binding protein, suggesting a role for the β9-10 surface in mediating protein-protein interactions for efficient Sas-4-PCM scaffold centriole tethering. Hence, we provide possible insights into how centrosomal protein defects result in human MCPH and how Sas-4 proteins act as a vehicle to tether PCM complexes to centrioles independent of its well-known role in centriole duplication.


Development of the Nurse Attitude Scale short form: factor analysis in a large sample of Japanese psychiatric clinical staff.
The Nurse Attitude Scale (NAS) measures nurses' Expressed Emotion. A short form of the NAS was developed and its reliability and validity examined. After performing factor analysis using 1252 samples, three factors were extracted. Cronbach's alpha for individual subscales was 0.852 for Hostility, 0.846 for Criticism and 0.645 for Positive Remarks. There was a significant correlation between individual subscales in the NAS short form and corresponding subscale in the Maslach Burnout Inventory (P < 0.001). The NAS short form seems to have acceptable reliability and validity.


Distinct expression of cytokines and mitogenic inhibitory factors in semen of fertile and infertile men.
To assess the effect of seminal plasma (SP) of fertile and infertile men on leukocyte mitogenic response, and the capability of sperm cells to produce IL-1. This study included four groups: fertile men (donors, normal), infertile men with azoospermia (azoo), oligo-terato-asthenozoospermia (OTA), and OTA with genital infection (OTA-inf). Mouse spleen cell proliferation in response to lipopolysaccharide (LPS) or Concanavalin-A (Con-A) was examined in the presence of SP from the above four groups. Supernatants (sup) and lysates (lys) of sperm cells from fertile and oligoteratoasthenospermic (OTA) men were evaluated for IL-1 bioactivity by specific bioassay. Seminal plasma (SP) of the four groups were shown to inhibit the mitogenic response of mouse spleen cells to LPS and Con-A. SP of fertile men was significantly more inhibitory than SP from infertile men. Sperm cells from fertile and OTA infertile men constitutively produced IL-1. Sperm cells of both groups produced similar levels of IL-1 as examined in the supernatants and lysates. Seminal plasma of fertile men had more inhibitory mitogenic activity than that of OTA. Sperm cells constitutively produce IL-1. It is possible that the factors involved in this inhibition are not only anti-proliferative immune factors. Cytokines and inhibitory factors of mitogenesis in the seminal plasma may be involved in the physiology and pathophysiology of sperm functions and thus affect male fertility.


A Brief History of Schizosaccharomyces pombe Research: A Perspective Over the Past 70 Years.
Since its humble start as a model organism in two European laboratories in the 1940s and 1950s, the fission yeast Schizosaccharomyces pombe has grown to become one of the best-studied eukaryotes today. This article outlines the way in which interest in S. pombe developed and spread from Europe to Japan, North America, and elsewhere from its beginnings up to the first International Meeting devoted to this yeast in 1999. We describe the expansion of S. pombe research during this period with an emphasis on many of the individual researchers involved and their interactions that resulted in the development of today's vibrant community.


Catalysis of a protein folding reaction: thermodynamic and kinetic analysis of subtilisin BPN' interactions with its propeptide fragment.
The in vivo folding of subtilisin is dependent on a 77 amino acid propeptide, which is eventually cleaved from the N-terminus of subtilisin to create the 275 amino acid mature form of the enzyme (Ikemura et al., 1987). We have cloned, expressed, and purified large quantities of the 77 amino acid subtilisin propeptide. This has enabled us to characterize its participation in the subtilisin folding reaction by spectroscopic and microcalorimetric methods. Unfolded subtilisin, when returned to native conditions, is kinetically isolated from its native state. Folding of subtilisin with the native calcium site-A is extremely slow even in the presence of a high concentration of isolated propeptide. The folding of a calcium-free mutant subtilisin, however, is readily catalyzed by the isolated propeptide. The propeptide-subtilisin folding reaction can be described as the following equilibrium: P(u) + S(u)<==>P-S<==>Pf-Sf<==>P(u) + Sf, where S(u) and P(u) are subtilisin and propeptide, respectively, which are largely unstructured at the start of the reaction; P-S is a collision complex of unfolded subtilisin and propeptide; Pf-Sf is the complex of folded subtilisin and propeptide; and Sf is folded subtilisin. The rate-limiting step in the folding reaction of calcium-free mutant subtilisin is formation of the initial collision complex, P-S. The rate at which P(u) and S(u) form a productive collision complex is approximately 500 M-1 s-1. The collision complex appears to be an early folding unit which, once formed, results in rapid isomerization to the fully folded complex. The rate constant for isomerization of the collision complex to the folded complex is > or = 0.5 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)


Polydimethylsiloxane pressure sensors for force analysis in tension band wiring of the olecranon.
Several different surgical techniques are used in the treatment of olecranon fractures. Tension band wiring is one of the most preferred options by surgeons worldwide. The concept of this technique is to transform a tensile force into a compression force that adjoins two surfaces of a fractured bone. Currently, little is known about the resulting compression force within a fracture. Sensor devices are needed that directly transduce the compression force into a measurement quality. This allows the comparison of different surgical techniques. Ideally the sensor devices ought to be placed in the gap between the fractured segments. The design, development and characterization of miniaturized pressure sensors fabricated entirely from polydimethylsiloxane (PDMS) for a placement within a fracture is presented. The pressure sensors presented in this work are tested, calibrated and used in an experimental in vitro study. The pressure sensors are highly sensitive with an accuracy of approximately 3 kPa. A flexible fabrication process for various possible applications is described. The first in vitro study shows that using a single-twist or double-twist technique in tension band wiring of the olecranon has no significant effect on the resulting compression forces. The in vitro study shows the feasibility of the proposed measurement technique and the results of a first exemplary study.


Age at menarche and the risk of gestational diabetes mellitus: a systematic review and meta-analysis.
Epidemiological studies had demonstrated that early age at menarche increased the risk of type 2 diabetes (T2DM), and gestational diabetes mellitus (GDM) shares many risk factors and features with T2DM. Thus, age at menarche may be a potential factor in the development of GDM. The aim of this study was to assess the association between age at menarche and the risk of gestational diabetes mellitus. The databases of PubMed, Embase, Web of Science and Cochrane Library were searched up to June 2017. A total of 50,535 participants from five individual studies were included in the meta-analyses to evaluate the risk of GDM. Meta-analysis showed that women with menarche at an early age (≤11 years) had a higher GDM risk than those with menarche at age ≥12 years. (OR = 1.45, 95% CI = 1.26-1.68; P < .00001) There was low heterogeneity among the studies (Q = 6.4; P = 0.17; I2 = 38). This meta-analysis demonstrated that earlier menarche was strongly associated with an increased risk of GDM. A history of early age at menarche may help identify women at high risk of GDM and allow the implementation for the strategy of early prevention.


Effect of Intra-Medullar and Intra-Venous Infusions of Mesenchymal Stem Cells on Cell Engraftment by In-Vivo Cell Tracking and Osteoinductivity in Rabbit Long Bones: A Pilot Study.
Stem cell therapy can be an efficacious treatment option for bone fragility disorders (eg, osteogenesis imperfecta, disuse osteopenia, and osteoporosis), and successful cell therapy application may be dependent on optimal cell engraftment in target bones. The objective of this study was to compare the efficiency of intra-medullar and intra-venous delivery of mesenchymal stem cells (MSC) to improve cell engraftment rate, bone mineral density, and micro-architecture. By using six healthy juvenile New Zealand White rabbits, MSC were isolated from cancellous bone harvests and confirmed to have osteogenic capacity by inducing ectopic bone formation. The MSC were cultured, transduced by foamy viral vectors with marker genes for in vivo cell tracking, and expanded. All rabbits had one randomly selected limb receive intra-medullar infusion of 3×107 to 1×108 autologous MSC in the distal femur or the distal femur and proximal tibia. Two of six rabbits also received an intra-venous MSC infusion. At 28 days, MSC bone engraftment was assessed by PCR and the bone density and microstructure assessed by computed tomography and histomorphometry. The intra-medullar-infused MSC were detected in epiphysis or diaphysis of the distal femurs and/or proximal tibiae. Infused MSC comprised 0.01 to 0.3% of all cells in the bone tissues. The intra-venous-infused MSC were not detected in any location. Neither intra-medullar nor intra-venous MSC infusion altered bone volume, bone mineral density, or cortical bone porosity/thickness. Systemic biodistribution of intra-medullar-infused MSC was not evident. Our results indicated that intra-medullar infusion can be an effective cell delivery route for stem cell therapy potentially for orthopedic disorders, in preference to systemic administration. Further research is warranted to demonstrate an efficacy of intra-medullar MSC infusion on bone density and micro-architecture using animal models of bone disorders.


The Creation of Surrogate Models for Fast Estimation of Complex Model Outcomes.
A surrogate model is a black box model that reproduces the output of another more complex model at a single time point. This is to be distinguished from the method of surrogate data, used in time series. The purpose of a surrogate is to reduce the time necessary for a computation at the cost of rigor and generality. We describe a method of constructing surrogates in the form of support vector machine (SVM) regressions for the purpose of exploring the parameter space of physiological models. Our focus is on the methodology of surrogate creation and accuracy assessment in comparison to the original model. This is done in the context of a simulation of hemorrhage in one model, "Small", and renal denervation in another, HumMod. In both cases, the surrogate predicts the drop in mean arterial pressure following the intervention. We asked three questions concerning surrogate models: (1) how many training examples are necessary to obtain an accurate surrogate, (2) is surrogate accuracy homogeneous, and (3) how much can computation time be reduced when using a surrogate. We found the minimum training set size that would guarantee maximal accuracy was widely variable, but could be algorithmically generated. The average error for the pressure response to the protocols was -0.05±2.47 in Small, and -0.3 +/- 3.94 mmHg in HumMod. In the Small model, error grew with actual pressure drop, and in HumMod, larger pressure drops were overestimated by the surrogates. Surrogate use resulted in a 6 order of magnitude decrease in computation time. These results suggest surrogate modeling is a valuable tool for generating predictions of an integrative model's behavior on densely sampled subsets of its parameter space.


[The superiorities of applying comprehensive medical model in treating stroke in Chinese medicine hospitals].
To study the clinical effectiveness of applying comprehensive medical model in treating stroke in Chinese medicine (CM) hospitals. Totally 236 stroke inpatients were randomly assigned to the comprehensive treatment group (as the experimental group, 121 cases) and the conventional treatment group (as the control group, 115 cases). A standard comprehensive treatment mode was applied in the experimental group. The Chinese materia medica (CMM) or acupuncture was combined during the rehabilitation treatment. Traditional basic drug treatment method was applied in the conventional treatment group. The health education for patients and their families was launched non-systematically. The mortality, the occurrence rate of complications, short-term clinical effectiveness, as well as NIHSS, Barthel index (BI), and Oxford Handicap Scale (OHS) were compared between the two groups. Before treatment there was no statistical difference in NIHSS score, BI, or OHS score between the two groups (P > 0.05). On day 21 and 90 of the treatment, there was statistical difference in NIHSS score, BI, and OHS score (P < 0.01). Better results were obtained in the experimental group. On day 21 and 90 of the treatment, the total effectiveness rate was 80.99% and 88.43% in the experimental group, higher than that of the control group (61.74% and 72.17% respectively), showing statistical difference (P < 0.05, P < 0.01). The occurrence rate of common complications in the experimental group was obviously lower than that in the control group (30.58% vs 69.56%, P < 0.01). There was no statistical difference in the mortality between the two groups (P > 0.05). The application of the comprehensive medical model in treating stroke in CM showed better effects than using traditional basic drug treatment method. Treatment of stroke by CM showed superiorities.


Hardiness Mediates Stress and Impact Level in ED Nurses Who Experienced a Violent Event.
This secondary analysis examined the mediating effect of hardiness between stress and impact level in ED nurses who experienced a violent event. This correlational study was conducted from June to August 2014. We used the visual analog scale to measure stress level, the Impact of Event Scale-Revised to measure impact level after the violent event, and the Dispositional Resilience Scale to measure hardiness. We then analyzed mediating effects with the Sobel test. Data were collected in 31 emergency medical centers located in B city in Korea. Data from 321 ED nurses who experienced a violent event were analyzed. Most nurses (91.9%) were women, with a mean age of 28.73 years. The main outcome measure was the mediating effect of hardiness between stress and impact level after ED nurses experienced violence. We found that both violence-related stress (B = 0.22, P < .001) and hardiness (B = -0.33, P = .037) were significant predictors of impact level from a violent event. Based on results of a Sobel test, hardiness partially mediated the relationship between violence-related stress and impact level from a violent event (Z = 2.03, P = .044). Hardiness had an effect on reducing the impact level of ED nurses who had experienced a violent event and had a mediating role in mitigating their stress. Therefore, we recommend the development of an intervention program that emphasizes the improvement of hardiness in ED nurses.


Cell cycle regulators and hematopoiesis.
The cell cycle behavior of hematopoietic cells varies from extended quiescence to spectacular proliferation. Cell cycle regulators choreograph these transitions through variation in the makeup of cyclin-dependent kinase (cdk)-containing complexes and through alteration in protein expression levels and subcellular localization. The mechanisms through which cell cycle regulators couple proliferation, differentiation and survival is coming into sharper focus. Cdk-inhibitors, once thought of solely in terms of a checkpoint function on cycling, are now known to interact directly with proteins and pathways central to differentiation and apoptosis. By shuttling between binding partners committed to discrete functional pathways, cell cycle regulators may directly coordinate proliferation with differentiation, migration and apoptosis.


Post-tonsillectomy hemorrhage rates in children compared by surgical technique.
Despite the sheer number of pediatric tonsillectomies performed in the United States annually, there is no clear consensus as to which surgical technique is superior. One way to compare surgical techniques is to study the morbidity associated with each. We report postoperative hemorrhage rates, one of the frequently encountered major adverse events, as part of a retrospective chart review across four different surgical techniques. These surgeries involved either (1) Coblation, (2) Co-blation with partial suture closure of the tonsillar fossa, (3) diathermy, or (4) partial intracapsular tonsillectomy (PIT). Of the 7,024 children we evaluated, 99 (1.4%) experienced a postoperative hemorrhage that required a second surgery; hemorrhage occurred after 33 of the 3,177 Coblation-alone procedures (1.04%), 28 of the 1,633 Coblation with partial suture closure procedures (1.71%), 29 of the 1,850 diathermies (1.57%), and 9 of the 364 PIT procedures (2.47%). Statistical analysis of hemorrhage rates with each surgical technique yielded p values >0.05 in each case (Coblation alone and Coblation with partial suture closure: p = 0.29; diathermy: p = 0.47; PIT, p = 0.20). Based on these data, we conclude that none of these techniques is significantly superior in terms of decreasing the risk of post-tonsillectomy hemorrhage in children. Therefore, surgeons should continue to use the surgical procedure they are most familiar with to optimize recovery in the postoperative period.


The Aspergillus fumigatus cellobiohydrolase B (cbhB) promoter is tightly regulated and can be exploited for controlled protein expression and RNAi.
The utility of the Aspergillus fumigatus cellobiohydrolase cbhB promoter for controlled gene expression has been investigated. cbhB message was present at high levels in the presence of carboxymethylcellulose and undetected in the presence of glucose. A reporter construct using the cbhB promoter showed similar behaviour and gave lower message levels than the Aspergillus nidulans alcA promoter under repressing conditions. An RNAi construct driven by the cbhB promoter was used to down-regulate the alb1 gene; transformants showed low alb1 message levels and a loss-of-function phenotype with carboxymethylcellulose, while both wild-type message levels and phenotype were seen with glucose. The cbhB promoter is therefore tightly controlled and can be exploited for the study of A. fumigatus.


Phonological Encoding in Mandarin Chinese: Evidence from Tongue Twisters.
Models of connected speech production in Mandarin Chinese must specify how lexical tone, speech segments, and phrase-level prosody are integrated in speech production. This study used tongue twisters to test predictions of the two different models of word form encoding. Tongue twisters were constructed from 5 sets of characters that rotated pairs of initial segments or pairs of tones, or both, across format (ABAB, ABBA), and across position of the characters in four-character tongue twister strings. Fifty two native Mandarin Chinese speakers read aloud 120 tongue twisters, repeating each one six times in a row. They made a total of 3503 (2.34%) segment errors and 1372 (.92%) tone errors. Segment errors occurred on the onsets of the first and third characters in the ABBA but not ABAB segment-alternating tongue twisters, and on the onsets of the second and fourth characters of the tone-alternating tongue twisters. Tone errors were highest on the third and fourth characters in the tone-alternating tongue twisters. The pattern of tone errors is consistent with the claim that tone is associated to a metrical frame prior to segment encoding, while the format by position interaction found for the segment-alternating tongue twisters suggest articulatory gestures oscillate in segment production as proposed by gestural phonology.


Relationships between Contextual and Task Performance and Interrater Agreement: Are There Any?
Work performance is one of the most important dependent variables in Work and Organizational Psychology. The main objective of this paper was to explore the relationships between citizenship performance and task performance measures obtained from different appraisers and their consistency through a seldom-used methodology, intraclass correlation coefficients. Participants were 135 public employees, the total staff in a local government department. Jobs were clustered into job families through a work analysis based on standard questionnaires. A task description technique was used to develop a performance appraisal questionnaire for each job family, with three versions: self-, supervisor-, and peer-evaluation, in addition to a measure of citizenship performance. Only when the self-appraisal bias is controlled, significant correlations appeared between task performance rates. However, intraclass correlations analyses show that only self- (contextual and task) performance measures are consistent, while interrater agreement disappears. These results provide some interesting clues about the procedure of appraisal instrument development, the role of appraisers, and the importance of choosing adequate consistency analysis methods.


Enhanced contractility during relaxation of cat papillary muscle.
Contractility during relaxation of isometric tension was studied in isolated, electrically driven cat papillary muscle by interpolation of test extrasystoles, all of whichpartially fused with their antecedent (control) contractions, were separated by computer from the fused contractions and then analyzed. The time course of the restitutionof contractility during relaxation was defined by plotting maximal positive dT/dt andtime-to-peak tension of the computer-separated extrasystole versus delay preceding the extrasystole. The dT/dt and time-to-peak tension, which steadily decline with progressive prematurity between contractions, both increase again during late relaxation, become progressively greater still earlier in relaxation, peak shortly after peak isometric tension, and then again decline. This phase of an apparently enhanced contractilityduring relaxation is depressed in low Ca'++ and is transmitted into the postextrasystolic period (in which it is superimposed on the usual postextrasystolic potentiation). The possible contributions of variations in series-elastic component and contractile-element lengths, actionpotential characteristics, and other factors on contractility during relaxation are discussed. It is suggested that enhanced contractility during relaxation may also be related in part to the decay of the intracellular free Ca'++ transient.


Mass Spectral and Chromatographic Studies on Some Halogenatedphenyl-2-Piperazinopropanones.
Gas chromatography-mass spectrometry (GC-MS) studies on the halogenatedphenyl-2-piperazinopropanones (XPPPOs): Twelve XPPPOs were subdivided into four groups of compounds and studied using GC-MS. The four studied groups include the three ring-substituted fluorophenylpiperazinopropanones, chlorophenylpiperazinopropanones, bromophenylpiperazinopropanones and trifluoromethylphenylpiperazinopropanones. The three compounds in each group have equal mass and many common mass spectral fragment ions. Perfluoroacylation of the secondary amine nitrogen of these isomeric piperazines gave mass spectra with differences in relative abundance of some fragment ions but acylation did not alter the fragmentation pathway and did not provide additional MS fragments of discrimination among these isomers. The perfluoroacyl derivatives of these piperazines were resolved on a stationary phase of 100% trifluoropropyl methyl polysiloxane (Rtx-200).


Building a safety culture.
In 2005-6, the NHS Litigation Authority (NHSLA) reported 40 claims of wrong site surgery, at a financial cost in excess of GBP1 million and unquantifiable and unimaginable emotional, physical and social cost to those directly affected. While wrong site surgery is described as relatively rare within the UK when set against the total number of procedures performed, when further considered under the wider umbrella of 'surgical harm' (which includes surgical site infection, patient identification errors, drug errors, failures in appropriate DVT/PE prophylaxis, etc) we are experiencing a worrying trend of increasing harm and patient failure.


Nonlinear dynamics of upward propagating flames.
We study the influence of gravity on the dynamics of upward propagating premixed flames. We show that the role of gravity on the dispersion relation is small, but that the nonlinear effects are large. Using a Michelson Sivashinsky equation modified with a gravity term, it can be observed that the nonlinear dynamics of the crests is greatly influenced by gravity, as well as the final amplitude of the flame. A simple model is proposed to explain the role of gravity on the amplitude.


Alkaline dissolution of starch facilitated by microwave heating for analysis by size-exclusion chromatography.
A rapid, straightforward starch dissolution method was developed to facilitate analysis of starch by size-exclusion chromatrography (SEC). Soft wheat starch was dispersed in 6 M urea and 1 M KOH and subjected to heating for 35, 45, or 60 s in a microwave oven as a potential means of starch dissolution. An increase in microwave heating time enhanced starch solubility but resulted in a steady decrease in amylopectin peak area and a consequent, artifactual increase in the amylose peak area due to molecular degradation. However, microwave heating for 35 s afforded a reasonable separation of starch fractions by SEC while minimizing molecular degradation of starch in comparison to a traditional starch dissolution procedure. This procedure provides a fast (<30 min), simple, and reproducible starch dissolution method for preparation of starches for SEC analysis and represents the first successful report of direct dissolution of granular starch via microwave heating.


Evolution of fatty acid taste in drosophilids.
Comparative studies of related but ecologically distinct species can reveal how the nervous system evolves to drive behaviors that are particularly suited to certain environments. Drosophila melanogaster is a generalist that feeds and oviposits on most overripe fruits. A sibling species, D. sechellia, is an obligate specialist of Morinda citrifolia (noni) fruit, which is rich in fatty acids (FAs). To understand evolution of noni taste preference, we characterized behavioral and cellular responses to noni-associated FAs in three related drosophilids. We find that mixtures of sugar and noni FAs evoke strong aversion in the generalist species but not in D. sechellia. Surveys of taste sensory responses reveal noni FA- and species-specific differences in at least two mechanisms-bitter neuron activation and sweet neuron inhibition-that correlate with shifts in noni preference. Chemoreceptor mutant analysis in D. melanogaster predicts that multiple genetic changes account for evolution of gustatory preference in D. sechellia.


Do we need USPs?
Australia is lacking the vital data relating to current practices needed to perform a meaningful evaluation of the quality of care in general practice. This article proposes that unannounced standardised patients (USPs) represent a valuable method of measuring actual performance in general practice. Constructive debate about the use of USPs may progress its acceptance as a valid tool for performance assessment and quality improvement.


[A rapid model of risk assessment of the biomechanical overload to the whole skeletal system].
A tool easy to apply is presented that can be used in ergonomic analysis of 1st level to identify the risk factors of biomechanical overload of the skeletal structures. The model is an evolution of a previous proposal, published in 2001, which was aimed at evaluation of the only upper arms: the present model also permits the evaluation of the spine (cervical and torso-lumbar tract) and of the inferior arms. A red flag judgement criterion has been maintained and, if an item is marked, there is the possibility to recognise the cause of the ergonomic criticality and to plan the correction according to a scale of ergonomic priority. The aim of this communication is to stimulate a wide participation in the project to develop a model for the risk assessment of biomechanical overload to the whole skeletal system.


Purification and properties of a beta-galactoside-binding lectin from neonatal marmoset.
A beta-galactoside-binding lectin was extracted from whole neonatal marmoset homogenate with lactose solution and purified to homogeneity by ion-exchange chromatography on Q Sepharose Fast Flow and by affinity adsorption to trypsinized and glutaraldehyde-fixed ghosts of rabbit erythrocytes. The lectin has a dimeric structure composed of two 15K subunits. Its amino acid composition and partial amino acid sequences were quite similar to those of beta-galactoside-binding lectins from human placenta and lung.


Fast MR imaging in obstetrics.
Ultrasonography (US) is the initial imaging modality of choice for evaluation of patients in obstetrics. However, the results of US are not always sufficient. Magnetic resonance (MR) imaging, which uses no ionizing radiation, may be an ideal method for further evaluation. Although MR imaging is not recommended during the first trimester and use of contrast material is not recommended in pregnant patients, fast MR imaging is useful in various obstetric settings and can provide more specific information with excellent tissue contrast and multiplanar views. In pregnant patients with acute conditions, various diseases (eg, red degeneration of a uterine leiomyoma) may be diagnosed. MR imaging allows characterization of pelvic masses discovered during pregnancy and diagnosis of postpartum complications (eg, abscess, hematoma, ovarian vein thrombosis). In pregnant patients with hydronephrosis, MR urography can demonstrate the site of obstruction and the cause (eg, a ureteral stone). MR pelvimetry may be beneficial in cases of breech presentation. Contrast material-enhanced dynamic MR imaging allows one to evaluate the vascularity of a placental polyp, detect the viable component of a gestational trophoblastic tumor, and diagnose a uterine arteriovenous malformation. MR imaging enables diagnosis of rare forms of ectopic pregnancy and early diagnosis of ectopic pregnancy.


Dual functionality of Trichoderma: Biocontrol of Sclerotinia sclerotiorum and biostimulant of cotton plants.
Microbial crop protection products based on Trichoderma have the ability to display multifunctional roles in plant protection, such as pathogen parasitism, enhance nutrient availability and stimulate plant growth, and these traits can be used to enhance the overall agronomic performance of a variety of crops. In the current study, we explored the multifunctional potential of two indigenous Brazilian strains of Trichoderma (T. asperelloides CMAA 1584 and T. lentiforme CMAA 1585) for their capability of controlling Sclerotinia sclerotiorum, a key plant pathogen of cotton, and for their ability of growth promotion in cotton plants (Gossypium hirsutum). Both strains were able to solubilize mineral phosphorus (CaHPO4), to release volatile organic compounds that impaired the mycelial growth of S. sclerotiorum, and to promote the growth of cotton plants under greenhouse conditions. In dual culture, Trichoderma strains reduced the growth rate and the number of sclerotia formed by S. sclerotiorum. By treating sclerotia with conidial suspensions of these Trichoderma strains, a strong inhibition of the myceliogenic germination was observed, as a result of the marked mycoparasitic activity exerted on the sclerotia. The parasitism over S. sclerotiorum was more effective with T. asperelloides CMAA 1584, whilst the biostimulant effects on cotton growth were more pronounced with T. lentiforme CMAA 1585, which also showed a higher capacity of phosphate solubilization. Thus, T. asperelloides CMAA 1584 displays higher efficiency in controlling S. sclerotiorum, while T. lentiforme CMAA 1585 is more suitable as a biostimulant due to its ability to promote growth in cotton plants. Overall, these Trichoderma strains may be used in mixture to provide both pathogen control and promotion of plant growth, and this strategy will support growers in minimizing the use of synthetic fertilizers and fungicides against white mold in cotton crops.


Malignancies in the acquired immunodeficiency syndrome.
Malignancies frequently arise in patients infected with human immunodeficiency virus (HIV), including those patients classified as having the acquired immunodeficiency syndrome (AIDS). Currently, Kaposi's sarcoma and certain types of lymphoma are considered to develop as a result of HIV infection, and other cancers have also been reported in these patients. For the most part, ultrastructural study of HIV-associated malignancies has been limited to Kaposi's sarcoma; the ultrastructural features of the epidemic form of this disease are generally the same as those of the classical form. The occurrence of these cancers in HIV-infected individuals appears to be related to the immunodeficiency caused by this virus, but the basic etiologic mechanisms remain unknown. In general, only palliative treatments are presently available for HIV-associated malignancies.


General trauma in a pediatric emergency department: spectrum and consultation patterns.
To assess the consultation patterns of pediatric emergency physicians in the management of injured children and to describe the spectrum of pediatric trauma, we retrospectively reviewed 601 patients treated in the emergency department for injuries during four one-week periods at a designated level I regional pediatric trauma center (50,000 patients/year) with a pediatric emergency medicine fellowship. The majority (94%) of pediatric trauma was minor; only 2% of children had injuries severe enough to require direct transfer to the operating room. The highest volume of patients, the greatest number of consultations, and the majority of admissions to the operating room occurred between 4 PM and midnight. No patients went to the operating room on the night shift. Musculoskeletal injuries constituted the predominant category of pediatric trauma, and lacerations were the most common specific injury. One half of all procedures involved laceration repair, and one third involved splinting or casting. Four hundred ten patients (68%) were managed by physicians in the emergency department without consultation. The orthopedic service performed one half of all consultations and admitted the largest number of patients; the majority of patients taken directly to the operating room had musculoskeletal injuries.(ABSTRACT TRUNCATED AT 250 WORDS)


An autoreactive T cell clone generated in the autologous mixed lymphocyte reaction in a patient with gastric carcinoma.
Autoreactive T cell clones were established from a patient with early gastric carcinoma and a healthy control in order to investigate the mechanism of suppression of autologous mixed lymphocyte reaction (AMLR) and its significance in immune surveillance against tumor. Clone 3F6 from the gastric carcinoma patient responded to only autologous non-T cells with less reactivity than 4 clones from the control subject. The proliferative response of clone 3F6 to interleukin-2 and immobilized anti-CD3 antibody was also suppressed when compared with the control clones. Autoreactive T cells were able to kill tumor cells and autologous PHA-blasts. The cytotoxic activity of clone 3F6 was also markedly suppressed when compared with the control clones. This data suggests that autoreactive T cells may be impaired in cancer patients and that this immunological disorder might cause the defective immune surveillance against tumors.


Site-specific nitration differentially influences tau assembly in vitro.
Previously, we reported that the microtubule-associated tau protein, the major constituent of neurofibrillary tangles (NFTs) in Alzheimer's brain, undergoes site-selective nitration by peroxynitrite (ONOO-) and that this event inhibits tau polymerization in vitro [Reynolds et al. (2005) Biochemistry 44, 1690-1700]. In the present study, we extend our analysis of tau nitration to include mutant tau proteins singly nitrated at each residue targeted by ONOO- in vitro (Tyr18, Tyr29, Tyr197, and Tyr394). Using our polymerization paradigm, we demonstrate that site-specific Tyr nitration differentially alters the rate and/or extent of tau assembly and generates robust changes in filament morphology. As determined by quantitative electron microscopy, select nitration of residues Tyr29 and Tyr197 increases the average length of synthetic tau filaments but does not alter the steady-state polymer mass. In contrast, site-specific nitration of residues Tyr18 and Tyr394 decreases the average length and/or number of synthetic filaments, resulting in a significant reduction in filamentous mass and an increase in tau critical concentration. Intriguingly, affinity measurements demonstrate that nitrative modifications do not preclude formation of the Alz-50 epitope, a pathological tau conformation detectable in authentic paired helical filaments (PHFtau). In fact, the Alz-50 antibody binds filaments assembled from nitrated mutant tau with higher avidity than wild-type filaments, even in instances where the overall filamentous mass is reduced. Taken together, our results suggest that site-specific nitration modulates the nucleation and/or elongation capacity of assembly-competent tau and that assumption of the Alz-50 conformation may be necessary, but not sufficient, to induce filament formation.


Campylobacter spp. and Salmonella spp. in black-headed gulls (Larus ridibundus).
Cloacal examination of 41 juvenile black-headed gulls (Larus ridibundus) by cultivation demonstrated Campylobacter jejuni in 26 (63%) and Salmonella typhimurium in 21 (51%) of them. All the bird samples were collected in a breeding colony near the town Hodonin, South Moravia, Czech Republic in 1996. Twenty six Campylobacter isolates were tested for antibiotic and drug sensitivity: all were resistant to at least three agents (Penicillin, Tetracyclin and Sulfomethoxazol-trimethoprim) while all were sensitive to Augmentan, Cefotaxim, Ciprofloxacin, Erythromycin, Nitrofurantoin and Cephazidine. Four percent of isolates were resistant to Ampicillin and Nalidixic acid. Of the 21 S. typhimurium isolates tested, 33% were sensitive to all drugs assayed, proportions of the strains resistant to Sulfomethoxazol-trimethoprim, Tetracyclin and Streptomycin were 58%, 16% and 8%, respectively.


Loss of H2 histamine receptor activity in rabbit aorta after maturity.
The activity of H1 and H2 histaminergic receptors was studied in aortic strips taken from young (6 weeks) and mature (7-8 months) rabbits. H1-mediated contractile activity was similar in both age groups, but H2 receptor relaxant activity was greatly diminished in mature rabbits. H2 receptor activity was evaluated with two experimental approaches: its modifying effect on blockade of H1 receptors by diphenhydramine (DPN), and its capacity to directly relax precontracted strips. Schild plot evaluation of DPN blockade revealed that the slope of the plot was below 1.0 in strips from young rabbits (0.77), but not in strips from mature rabbits (0.94). Propranolol pretreatment did not increase the Schild plot slope (0.66) of young aortic strips, but metiamide pretreatment did (0.92). Metiamide treatment did not further in crease slope of mature strips (0.95). When the slopes of the plots were near 1.0, as in the mature and metiamide-treated mature and young strips, the pA2 of DPN was very close (7.51, 7.70, and 7.65). Lost H2 receptor activity in maturity was confirmed by relaxing norepinephrine-precontracted strips with histamine or dimaprit. Histamine-induced relaxation of precontracted strips was slightly diminished in mature strips, while the relaxing activity of dimaprit was greatly reduced in mature tissue. The same strips relaxed vigorously when exposed to nitroglycerin or NaNO2, demonstrating that the strips were capable of relaxing. Therefore, it appears that H2 receptor activity in rabbit aorta is greatly diminished as the animal matures.


Identification and Characterization of BmNPV m6A Sites and Their Possible Roles During Viral Infection.
Bombyx mori nucleopolyhedrovirus (BmNPV) is one of the most serious pathogens and causes serious economic losses in sericulture. At present, there is no epigenetic modification of BmNPV transcripts, especially of m6A, and this modification mediates diverse cellular and viral functions. This study showed that m6A modifications are widespread in BmNPV transcripts in virally infected cells and the identified m6A peaks with a conserved RRACH sequence. m6A sites predominantly appear in the coding sequences (CDS) and the 3'-end of CDS. About 37% of viral genes with m6A sites deleted from the viral genome did not produce any infectious virions in KOV-transfected cells. Among the viral genes related to replication and proliferation, ie-1 mRNA was identified with a higher m6A level than other viral genes. The m6A sites in the ie-1 mRNA may be negatively related to the protein expression. Viral replication was markedly inhibited in cells overexpressed with BmYTHDF3 in a dose-dependent manner, and a contrary effect was found in si-BmYTHDF3-transfected cells. Collectively, the identification of putative m6A modification in BmNPV transcripts provides a foundation for comprehensively understanding the viral infection, replication, and pathobiology in silkworms.


Health behaviors according to the ability to understand health information in Korean adults.
This study aimed to verify the relationship between the level of understanding of health information and health behaviors among Korean adults. In total, 228 984 adults who participated in the 2021 Korea Community Health Survey were included. Participants were divided into three groups according to age (19-44, 45-64 and 65+). The ability to understand verbal and written health information was included, and its association with health behaviors, including smoking, alcohol consumption and preventive health service uptake, was assessed. Associations between the ability to understand health information and health behaviors were analyzed using chi-squared tests and multiple logistic regression analyses. Approximately 22.7% and 20% of the participants responded that verbal and written health information were easy to understand, respectively, with significant differences by age group. Compared to those with easy-to-understand verbal health information, those with difficulty in understanding had a higher risk of current cigarette smoking and monthly drinking and were less likely to engage in more than moderate physical activity, walking, influenza vaccination in 1 year, cancer examination in 2 years and medical examination in 2 years. Difficulty in understanding or no interest in written health information was also associated with unhealthy behaviors. A strong ability to understand health information is related to positive health behaviors. However, there are differences in the associations by age group, which should be considered when establishing a health literacy improvement strategy. These findings could promote health literacy and ultimately contribute to helping individuals make better choices for positive health behaviors.


Healthcare use by children with attention deficit/hyperactivity disorder with and without psychiatric comorbidities.
This study examined healthcare services used by children with attention-deficit/hyperactivity disorder (ADHD), with and without psychiatric comorbidities. The study was conducted in a large health maintenance organization in the Pacific Northwest on all continuously enrolled children aged 5 to 12 from January 1997 through July 1998. The study measured all outpatient medical care, specialty mental health care services, and prescription drug dispensings from computer records. Children with ADHD, with and without other psychiatric comorbidities, use more general medical services than do other groups of children, including outpatient visits, acute care (emergency room [ER] urgent care) visits. ADHD and other psychiatric comorbidities lead to higher use of specialty mental health services and greater use of psychotropic medications.


The relationship between bacteria and the abnormal follicular keratinization in acne vulgaris.
The structural organization and bacteriological profile of follicular casts and early comedones in prepuberal children were investigated. Follicular casts were present in all samples but were not as abundant as usually seen in older individuals with acne. When examined with the light microscope, all casts and comedones were composed of numerous layers of horny cells and sebum, but were devoid of bacteria. Neither follicular casts nor comedones yielded bacteria when cultured. Electron microscopy of the follicular casts revealed the presence of small round, discrete lipid droplets, and alternating dense and less dense lamellar configurations within the horny cells. Some horny cells closest to the sebum-filled lumen contained large lipid masses, resulting in "balloon-shaped" regions. Prepuberal follicular horny cells contained all of the abnormalities usually seen in follicular casts and biopsy material from acne patients, which suggests that these casts are potential comedones. These aberrations occurred in the complete absence of bacteria indicating that bacteria are not essential to the formation of casts or comedones. Furthermore, our findings indicate that bacteria play little if any role in the initial events of pathological keratinization.


Novel Cd(II) coordination polymers with flexible disulfoxide ligands: effects of ligand spacers, terminal groups and counter anions on the complex framework formations.
Five novel Cd(II) coordination polymers with three structurally related flexible disulfoxide ligands, [[Cd(L1)3](ClO4)2]n (1), [[Cd(L2)3](ClO4)2(CHCl3)]n (2), [Cd(L2)(NO3)2(H2O)]n (3), [Cd2(L3)2(NO3)4]n (4) and [[Cd(L3)3](ClO4)2]n (5), where L1= 1,3-bis(phenylsulfinyl)propane, L2= 1,4-bis(phenylsulfinyl)butane and L3= 1,4-bis(ethylsulfinyl)butane, were synthesized and structurally determined by X-ray diffraction. Complex 1 has a 2D layer structure, in which part of the L1 ligands bridge the Cd(II) ions to form double-bridging chains and the other part of ligands link such chains to form a 2D framework. Complexes 2 and 5 are isomorphous, showing unusual 2D (3,6) network structures containing triangular grids. Complex 3 adopts a 2D (4,4) network formed by L2 linking the NO3- bridged (Cd-O-N-O-)n 1D zigzag chains. By contrast, is a 1D chain, in which two Cd(II) centers are bridged by mu2-O of sulfoxide groups to form a dinuclear unit, and L3 ligands link such dinuclear units to form a 1D double-bridging chain. The structural differences among such complexes show that the ligand nature and counter anions have important influences on the complex structures, which may provide a rational method for controlling the framework formation in metal-organic coordination polymers.


Use of nicotinamide adenine dinucleotide (NAD)-dependent glucose-6-phosphate dehydrogenase in enzyme staining procedures.
Substitution of nicotinamide adenine dinucleotide dependent glucose-6-phosphate dehydrogenase for the nicotinamide adenine dinucleotide phosphate dependent enzyme has produced identical results in a number of enzyme-linked electrophoretic staining procedures. This substitution significantly reduces the cost of staining for adenylate kinase, creatine kinase, glucosephosphate isomerase, mannosephosphate isomerase, phosphoglucomutase, and pyruvate kinase activity by utilizing NAD rather than the more expensive NADP.


Is there a role for specialized enteral nutrition in the intensive care unit?
The enteral route is preferred for nutrition support of critically ill patients who have a functional gastrointestinal tract. A variety of specialized formulas are available to help manage the complications often seen in these patients. This review summarizes the literature supporting the use of formulas marketed for liver disease, wound healing, immune-system enhancement, pulmonary and renal disease, and diabetes mellitus. With the exception of the immune-enhancing formulas, convincing evidence for the use of these formulas in critically ill patients is lacking. Further studies are warranted.


Reversible, Covalent DNA Condensation Approach Using Chemical Linkers for Enhanced Gene Delivery.
Nonviral gene delivery has emerged as a promising technology for gene therapy. Nonetheless, these approaches often face challenges, primarily associated with lower efficiency, which can be attributed to the inefficient transportation of DNA into the nucleus. Here, we report a two-stage condensation approach to achieve efficient nuclear transport of DNA. First, we utilize chemical linkers to cross-link DNA plasmids via a reversible covalent bond to form smaller-sized bundled DNA (b-DNA). Then, we package the b-DNA into cationic vectors to further condense b-DNA and enable efficient gene delivery to the nucleus. We demonstrate clear improvements in the gene transfection efficiency in vitro, including with 11.6 kbp plasmids and in primary cultured neurons. Moreover, we also observed a remarkable improvement in lung-selective gene transfection efficiency in vivo by this two-stage condensation approach following intravenous administration. This reversible covalent assembly strategy demonstrates substantial value of nonviral gene delivery for clinical therapeutic applications.


Using machine learning to identify early predictors of adolescent emotion regulation development.
As 20% of adolescents develop emotion regulation difficulties, it is important to identify important early predictors thereof. Using the machine learning algorithm SEM-forests, we ranked the importance of (87) candidate variables assessed at age 13 in predicting quadratic latent trajectory models of emotion regulation development from age 14 to 18. Participants were 497 Dutch families. Results indicated that the most important predictors were individual differences (e.g., in personality), aspects of relationship quality and conflict behaviors with parents and peers, and internalizing and externalizing problems. Relatively less important were demographics, bullying, delinquency, substance use, and specific parenting practices-although negative parenting practices ranked higher than positive ones. We discuss implications for theory and interventions, and present an open source risk assessment tool, ERRATA.


The effects of losartan on renal function in the newborn rabbit.
The low GFR of newborns is maintained by various factors including the renin-angiotensin system. We previously established the importance of angiotensin II in the newborn kidney, using the angiotensin-converting enzyme inhibitor perindoprilat. The present study was designed to complement these observations by evaluating the role of angiotensin-type 1 (AT(1)) receptors, using losartan, a specific AT(1)-receptor blocker. Increasing doses of losartan were infused into anesthetized, ventilated, newborn rabbits. Renal function and hemodynamic variables were assessed using inulin and para-aminohippuric acid clearances as markers of GFR and renal plasma flow, respectively. Losartan 0.1 mg/kg slightly decreased mean blood pressure (-11%) and increased diuresis (+22%). These changes can be explained by inhibition of the AT(1)-mediated vasoconstrictive and antidiuretic effects of angiotensin, and activation of vasodilating and diuretic AT(2) receptors widely expressed in the neonatal period. GFR and renal blood flow were not modified. Losartan 0.3 mg/kg decreased mean blood pressure significantly (-15%), probably by inhibiting systemic AT(1) receptors. GFR significantly decreased (-25%), whereas renal blood flow remained stable. The decrease in filtration fraction (-21%) indicates predominant efferent vasodilation. At 3 mg/kg, the systemic hypotensive effect of losartan was marked (mean blood pressure, -28%), with decreased GFR and renal blood flow (-57% and -51%, respectively), a stable filtration fraction, and an increase in renal vascular resistance by 124%. The renal response to this dose can be considered as reflex vasoconstriction of afferent and efferent arterioles, rather than specific receptor antagonism. We conclude that under physiologic conditions, the renin-angiotensin is critically involved in the maintenance of GFR in the immature kidney.


Life during lockdown: a qualitative study of low-income New Zealanders' experience during the COVID-19 pandemic.
This research explores the experience of low-income New Zealanders during the COVID-19 pandemic lockdown and their advice to the Government about addressing future pandemics. New Zealand had a rapid and effective lockdown that meant the virtual elimination of community transmission. Twenty-seven semi-structured interviews were undertaken with low-income people in June-July 2020 immediately after lockdown was lifted. Life during lockdown was challenging for study participants. They were fearful of the virus and experienced mental distress and isolation. Most participants felt safe at home and reported coping financially while still experiencing financial stress. Participants were resourceful and resilient. They coped with lockdown by using technology, self-help techniques and support from others. New Zealand's welfare state ensured participants had access to health services and welfare payments, but there were challenges. Welfare payments did not fully meet participants' needs, and support from charitable organisations was critical. Participants were overwhelmingly positive about the Government's response and advised the Government to take the same approach in the future. This is a particularly reassuring finding from some of the most vulnerable New Zealanders. An early and hard lockdown, the welfare state, compassion and clearly communicated leadership were keys to a successful lockdown for the low-income people in this study. Research of the experience of low-income people during pandemics is critical to ensuring inequities in pandemic impact are mitigated.


Stress and the immune response in rats.
The in vitro response of sensitized splenic lymphocytes to antigen (thyroglobulin) was increased by crowding and decreased by isolation in female rats. Both isolated and crowded male rats responded by a decrease in the in vitro reactivity of lymphocytes to antigen. The response of the lymphocytes to PHA was not altered in any consistent manner. Similar animals, both control and those immunized with thyroglobulin, were tested for an effect of in vivo injections of epinephrine on the in vitro reactivity of lymphocytes; epinephrine was given intraperitoneally 30 min before the rats were killed for removal of spleens. Incorporation of 3H-thymidine by lymphocytes was greater in control cultures (neither PHA nor antigen present) but there was a decreased response to either PHA or antigen when epinephrine had been injected.


Degradation of xenobiotic compounds in situ: capabilities and limits.
Exploiting microorganisms for remediation of waste sites is a promising alternative to groundwater pumping and above ground treatment. The objective of in situ bioremediation is to stimulate the growth of indigenous or introduced microorganisms in regions of subsurface contamination, and thus to provide direct contact between microorganisms and the dissolved and sorbed contaminants for biotransformation. Subsurface microorganisms detected at a former manufactured gas plant site contaminated with coal tars mineralized significant amounts of naphthalene (8-43%) and phenanthrene (3-31%) in sediment-water microcosms incubated for 4 weeks under aerobic conditions. Evidence was obtained for naphthalene mineralization (8-13%) in the absence of oxygen in field samples. These data suggest that biodegradation of these compounds is occurring at the site, and the prospects are good for enhancing this biodegradation. Additional batch studies demonstrated that sorption of naphthalene onto aquifer materials reduced the extent and rate of biodegradation, indicating that desorption rate was controlling the biodegradation performance.


Perceived healthcare quality and contraception utilization among persons recently incarcerated.
Previously incarcerated women have specific gender and physiologic needs that are poorly addressed on community re-entry. The objective of this study is to evaluate the relationship between contraception use and perceived healthcare quality post-incarceration. Additionally, we examine the association between social determinants of health and contraception use post-incarceration. A secondary analysis of a cross-sectional study of reproductive-aged women with a history of criminal-justice involvement in three cities (n = 383) was performed. Questions related to demographics, social determinants of health, sexual and reproductive health practices, health services use, and healthcare quality were analyzed. Bivariate analysis and logistic regression examined associations between these variables and contraception utilization among persons recently incarcerated. 35% of the participants used a method to prevent pregnancy. There were no significant differences noted between contraceptive users and non-users in perceived healthcare quality. Participants who were not using a contraceptive method were more likely to lack health insurance and experience food insecurity when compared to contraceptive users. Although there was no difference in perceived healthcare quality between contraceptive users and non-users, significant barriers to contraceptive access on community re-entry exist. More studies are warranted to explore the sexual and reproductive health of previously incarcerated women.


Developing a citywide youth violence prevention plan: perceptions of various stakeholders.
Researchers suggest that violence prevention requires community-wide efforts and partnerships that demonstrate commitment to youth development. Missing from this research, however, are studies considering how these partnerships are formed and how members of various groups involved in these partnerships perceive youth violence prevention. This study sought to fill this void. A series of seven focus group interviews were conducted with 85 stakeholders involved in developing a youth violence prevention plan in one community. Results suggest that the stakeholders were optimistic about developing violence prevention strategies and forging partnerships between various groups. Participants pointed to specific themes that provide a framework for understanding youth violence prevention planning efforts. Implications are provided.


LMTK3 knockdown retards cell growth and invasion and promotes apoptosis in thyroid cancer.
Lemur tyrosine kinase-3 (LMTK3) is a member of the serine/threonine tyrosine kinase family, which is thought to be involved in tumor progression and prognosis. The purpose of the present study was to determine the diagnostic significance and therapeutic targets in thyroid cancer. ELISA assay was used to detect the protein expression of serum LMTK3. Immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction were employed to measure the expression of LMTK3. Flow cytometry was used to determine the cell cycle. Transwell assay was used to measure the invasion and migration of SW579 cells and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to detect cell apoptosis. The LMTK3 level was positively associated with disease stage and pathological type, whereas there was no correlation between LMTK3 level and gender, age, tumor size or lymph node metastasis. The serum LMTK3 level was significantly increased in 102 thyroid carcinoma patients compared with 52 benign thyroid tumor patients and 50 healthy volunteers (P=0.001). The protein and mRNA expression of LMTK3 was markedly higher in thyroid cancer patients compared with patients with benign thyroid tumors. Notably, LMTK3 knockdown retarded proliferation, invasion and migration in SW579 cells. In addition, downregulation of LMTK3 promoted apoptosis in SW579 cells. These findings indicated that LMTK3 knockdown retards the growth of thyroid cancer cells partly through inhibiting proliferation, invasion, migration and inducing apoptosis in SW579 cells. It may serve as a useful diagnostic biomarker and a novel therapeutic target for patients with thyroid cancer.


Vocal tract acoustics.
This paper considers the topic of vocal tract acoustics from the three perspectives: (a) the acoustic theory of speech production; (b) contemporary laboratory methods for acoustic analysis, and (c) measurement of the acoustic signal of speech. Linear source-filter theory is the standard acoustic theory of speech production and is the foundation for remarkable advances in the analysis and synthesis of speech. Digital signal processing, the dominant laboratory method for speech analysis, enables the acquisition and recording of the acoustic speech signal but also implements quantitative algorithms largely based on linear source-filter theory. Measurements of the acoustic signal reflect the acoustic theory of speech production, laboratory methods for signal analysis, and principles of experimental phonetics. Basic issues in the three domains of theory, laboratory methods, and measurement are summarized as they pertain to the interests of the voice scientist, voice clinician, and voice teacher.


CD80 and IL-2 signals cooperate in the regression of tumors transplanted in congenitally athymic mice.
Interleukin-2 and CD80 transfectants of a methylcholanthrene-induced murine sarcoma Mc12 (Mc12-IL-2 and Mc12-CD80 cells) with similar tumorigenicity in euthymic mice were utilized for experiments designed to investigate a co-stimulatory role of the CD80 molecule in allogeneic, congenitally athymic (nu/nu) mice. The CD80-transfected cells were as tumorigenic in nu/nu mice as the parental Mc12 sarcoma. The IL-2-transfected cells grew only transiently and regressed in all nu/nu recipients during four weeks after challenge with doses up to 5x10(7) cells. The 1:1 mixture of parental Mc12 with Mc12-CD80 cells grew progressively in all inoculated nu/nu mice; in a 1:1 mixture with parental Mc12 cells, Mc12-IL-2 cells were able to cause regressions in approximately 50% of nu/nu mice; the 1:1 mixture of Mc12-IL-2 and Mc12-CD80 transfectants showed only transient growth and regressed during four weeks in all inoculated nu/nu mice. Adoptive transfer of cell-mediated immunity revealed that spleen cells from tumor regressors were capable of transferring the resistance to Mc12 tumor in nu/nu mice. The spleen cells from tumor regressors were not cytolytic when allowed to react in vitro with Mc12, Mc12-IL-2, or Mc12-CD80 target cells. However, when grown in IL-2-containing medium, splenocytes from tumor regressors, but not the splenocytes from tumor progressors, could develop cytolytic activity directed against Mc12 target cells that was comparable to that of the splenocytes from tumor-free controls. These results suggest that the rejection of tumors in nu/nu mice was mediated by IL-2-dependent mechanisms in which the CD80 molecule played a co-stimulatory role; the results also indicate that the ability to be activated by IL-2 and to give rise to cytolytic activity of nu/nu splenocytes from tumor progressors is decreased.


The application of hyperthermia in regional chemotherapy.
To evaluate the role of hyperthermia combined with chemotherapy in the loco-regional treatment of tumors, a retrospective analysis was done with 228 limb melanoma patients treated with hyperthermic antiblastic perfusion (HAP). A series of treatment- and tumor-related prognostic factors was analyzed to establish their influence on tumor response, loco-regional control, and survival. Concerning tumor response, the logistic model showed that the number of lesions and the minimal tumor temperature (min T) maintained their individual predictive values (P < 0.000001 and P = 0.04, respectively). For loco-regional control, only the number of lesions had a significant predictive value. No direct correlation was found between the treatment-related variables and loco-regional control. However, the 5-year survival rate was significantly higher for patients who achieved a complete response (CR) (51.5%, P = 0.0033) as compared to those who did not (33.3%), providing indirect evidence of the role of the treatment. Multivariate analysis showed that both disease-free and overall survival are strongly influenced by numerous clinical variables and the min T always maintained its significance. When analyzing the subgroup of 119 patients evaluable for tumor response, the Cox model selected the tumor response as the dominant factor for both disease-free and overall survival. These data seem to demonstrate that the optimization of treatment parameters is crucial in determining the CR rate, which, in turn, positively affects the disease outcome. HAP is the treatment of choice for recurrent limb melanoma, and hyperthermia plays an important role in exploiting the efficacy of this technique.


Regulatory properties of the NH2- and COOH-terminal domains of troponin T. ATPase activation and binding to troponin I and troponin C.
The contraction of skeletal muscle is regulated by Ca2+ binding to troponin C, which results in an internal reorganization of the interactions within the troponin-tropomyosin complex. Troponin T is necessary for Ca2+-dependent inhibition and activation of actomyosin. Troponin T consists of an extended NH2-terminal domain that interacts with tropomyosin and a globular COOH-terminal domain that interacts with tropomyosin, troponin I, and troponin C. In this study we used recombinant troponin T and troponin I fragments to delimit further the structural and regulatory interactions with the thin filament. Our results show the following: (i) the NH2-terminal region of troponin T activates the actomyosin ATPase in the presence of tropomyosin; (ii) the interaction of the globular domain of troponin T with the thin filament blocks ATPase activation in the absence of Ca2+; and (iii) the COOH-terminal region of the globular domain anchors the troponin C-troponin I binary complex to troponin T through a direct Ca2+-independent interaction with the NH2-terminal region of troponin I. This interaction is required for Ca2+-dependent activation of the actomyosin ATPase activity. Based on these results we propose a refined model for the troponin complex and its interaction with the thin filament.


An in vitro study of silver and fluoride ions on remineralization of demineralized enamel and dentine.
The purpose of this study was to compare the effect of silver fluoride, silver nitrate and potassium fluoride on remineralization of demineralized enamel and dentine in vitro. Forty premolars were cut into cuboidal blocks. Acid-resistant varnish was painted onto each block to cover all surfaces, except two windows, one in enamel and one in dentine. The tooth blocks were placed in demineralizing solution for 96 hours. They were then randomly divided into four groups of 10 blocks each and immersed in solutions of AgF, AgNO(3), KF or water for 3 minutes. Afterwards, they were immersed in a remineralizing solution for 108 hours. Micro CT scanning was conducted before and after remineralization. The increase in linear attentuation coefficient (LAC) for the enamel lesions after remineralization was 1.08/cm, 0.95/cm, 0.86/cm and 0.60/cm in the AgF, AgNO(3), KF and control groups, respectively (ANOVA, p < 0.001; AgF, AgNO(3), KF > control; AgF > KF). The increase in LAC for the dentine lesions was 1.01/cm, 0.92/cm, 0.88/cm and 0.53/cm, respectively (ANOVA, p < 0.001; AgF, AgNO(3), KF > control). Topical application of silver or fluoride ions can increase the mineral density of demineralized enamel and dentine lesions during remineralization. The synergistic effect of silver and fluoride ions is relatively small.


An Assessment of Mental Health Status of Undergraduate Medical Trainees in the University of Calabar, Nigeria: A Cross-Sectional Study.
The mental health status of medical students has been proven to be poor compared to their peers in other disciplines and has led to grave personal and professional consequences. This subject has however remained largely unexplored in our medical school. The study was therefore conducted to assess the prevalence of mental health of medical students in the University of Calabar, Cross river state, Nigeria. A descriptive cross-sectional survey of 451 randomly selected medical students from the pre-clinical and clinical levels of study in the University of Calabar. A self administered questionnaire including the GHQ12 was used to elicit information from the respondents. A score of ≥ 3 suggested poor mental while a score < 3 represented good mental health. Data were summarized using proportions, and χ2 test was used to explore associations between categorical variables. Level of significance was set at p < 0.05. The mean age of the respondents was 23.4 ± 4.3 years, 63.8% were males, 34.8% were from the preclinical and 65.2% from clinical levels of study. Based on the GHQ categorisation, 39.2% had a poor mental health status, compared to 60.8% with good mental health status. The factors significantly associated with poor mental health, were recent experience of mistreatment by trainers or colleagues, perceived inadequate monthly allowance and perception that medical training is stressful (p < 0.05). With more than a third of undergraduate medical trainees with traits of poor mental health, provision of accessible mental health services/counselling is strongly recommended early in their training.


Metabolic effects of intermittent access to caloric or non-caloric sweetened solutions in mice fed a high-caloric diet.
Human consumption of obesogenic diets and soft drinks, sweetened with different molecules, is increasing worldwide, and increases the risk of metabolic diseases. We hypothesized that the chronic consumption of caloric (sucrose, high-fructose corn syrup (HFCS), maltodextrin) and non-caloric (sucralose) solutions under 2-hour intermittent access, alongside the consumption of a high-fat high-sucrose diet, would result in differential obesity-associated metabolic abnormalities in mice. Male C57BL/6 mice had ad libitum access to an HFHS diet and to water (water control group). In addition, some mice had access, 2h/day, 5days/week (randomly chosen) for 12weeks, to different solutions: i) a sucrose solution (2.1kJ/ml), ii) an HFCS solution (2.1kJ/ml), iii) a maltodextrin solution (2.1kJ/ml) and a sucralose solution (60mM) (n=15/group). Despite no changes in total caloric intake, 2h-intermittent access to the sucrose, HFCS or maltodextrin solutions led to increased body weight and accumulation of lipids in the liver when compared to the group consuming water only. The HFCS and sucrose solutions induced a higher fat mass in various fat depots, glucose intolerance, increased glucose oxidation at the expense of lipid oxidation, and a lower hypothalamic expression of NPY in the fasted state. HFCS also reduced proopiomelanocortin expression in the hypothalamus. 2h-intermittent access to sucralose did not result in significant changes in body composition, but caused a stronger expression of CART in the hypothalamus. Finally, sucrose intake showed a trend to increase the expression of various receptors in the nucleus accumbens, linked to dopamine, opioid and endocannabinoid signaling. In conclusion, 2h-intermittent access to caloric solutions (especially those sweetened with sucrose and HFCS), but not sucralose, resulted in adverse metabolic consequences in high-fat high-sucrose-fed mice.


HLA B27 negative ankylosing spondylitis--a rare condition.
New strict criteria have recently been suggested for the definition of HLA B27 negative ankylosing spondylitis, which show it to be less common than was previously thought. We report two cases which conform to the new criteria, together with details of family studies. The use of these criteria in future studies of B27 negative disease is discussed.


Breast cancer resistance protein and P-glycoprotein expression in patients with newly diagnosed and therapy-refractory ulcerative colitis compared with healthy controls.
Efflux transporters such as breast cancer resistance protein (BCRP/ABCG2) and P-glycoprotein (Pgp; MDR1/ABCB1) are protecting the enterocytes from potentially toxic compounds. Both transporters have been reported to be downregulated in patients with active ulcerative colitis (UC). The aim of this study was to evaluate transporter expression in both unaffected and inflamed mucosa of patients with active UC, in drug-naïve and treated patients with UC and compare the results with transporter expression in healthy subjects. Transporter expression was determined with real-time RT-PCR (TaqMan) in inflamed and unaffected mucosa of newly diagnosed (n = 12) and therapy-refractory (n = 11) patients with UC. Expression levels were compared with UC patients in remission (n = 11) and control subjects (n = 26). BCRP and Pgp expression was evaluated by immunohistochemistry. Compared with unaffected mucosa, BCRP expression was significantly reduced in inflamed mucosa of newly diagnosed drug-naïve patients with UC (expression reduced to 30%) as well as in patients not responding to treatment (reduced to 25%) with either 5-aminosalicylates (n = 7) or prednisone (n = 4). Unaffected mucosa of UC patients showed comparable transporter expression to unaffected mucosa of control subjects. MDR1 expression depicts a similar pattern. Protein staining for Pgp and BCRP was significantly reduced in the inflamed mucosa of patients with active UC. Expression of both efflux transporters BCRP and MDR1 is reduced, but only in inflamed tissue of patients with active UC. Transporter expression in unaffected mucosa of patients with active UC is comparable to healthy controls. The data suggest that the inflammatory process is responsible for the reduced levels. A major role in the pathogenesis of UC is unlikely.


Role of blood pressure monitoring in non-pharmacological management of hypertension.
Ambulatory blood pressure monitoring (ABPM) and home blood pressure (BP) measurement appear to be useful in the assessment of the effects of non-pharmacological treatment of hypertension because they can detect small changes in BP without observer bias. We studied the effects of various lifestyle modifications using ABPM and home BP measurement in Japanese patients with hypertension. Weight reduction by a hypocaloric diet (average 4 kg) was associated with decreases in 24-h BP (10/4 mmHg) as well as casual BP (9/6 mmHg). The reductions in daytime and night-time BPs were comparable. The effects of daily walking without weight loss on office, home, and 24-h BPs were 2-3/1-2 mmHg. The changes in home and 24-h BPs were more significant than those in office BP. A low-salt diet (25 mmol/day versus 250 mmol/day) decreased 24-h BP by 9/4 mmHg. This hypotensive effect was observed throughout the day. Potassium supplementation (64 mmol/day) decreased office, home and 24-h BPs by 3-4/1-2 mmHg. The changes in home and 24-h BPs were highly significant compared with office BP. Supplementation of magnesium (20 mmol/day) also reduced those BPs significantly. However, the effects of calcium supplementation (25 mmol/day) were small (1-2/1 mmHg) and were significant only for home BP. Alcohol restriction for 4 weeks decreased daytime BP by 3/2 mmHg but increased night-time BP by 4/2 mmHg. Average 24-h BP did not change. Smoking cessation lowered daytime BP without affecting night-time BP. Monitoring of 24-h BP and home BP can detect small changes in BP produced by lifestyle modifications. Ambulatory BP monitoring is particularly suitable in the assessment of changes in lifestyle affecting the circadian pattern of BP such as alcohol consumption and smoking.