Evolution Analysis of the Fasciclin-Like Arabinogalactan Proteins in Plants Shows Variable Fasciclin-AGP Domain Constitutions.
The fasciclin-like arabinogalactan proteins (FLAs) play important roles in plant development and adaptation to the environment. FLAs contain both fasciclin domains and arabinogalactan protein (AGP) regions, which have been identified in several plants. The evolutionary history of this gene family in plants is still undiscovered. In this study, we identified the FLA gene family in 13 plant species covering major lineages of plants using bioinformatics methods. A total of 246 FLA genes are identified with gene copy numbers ranging from one (Chondrus crispus) to 49 (Populus trichocarpa). These FLAs are classified into seven groups, mainly based on the phylogenetic analysis of plant FLAs. All FLAs in land plants contain one or two fasciclin domains, while in algae, several FLAs contain four or six fasciclin domains. It has been proposed that there was a divergence event, represented by the reduced number of fasciclin domains from algae to land plants in evolutionary history. Furthermore, introns in FLA genes are lost during plant evolution, especially from green algae to land plants. Moreover, it is found that gene duplication events, including segmental and tandem duplications are essential for the expansion of FLA gene families. The duplicated gene pairs in FLA gene family mainly evolve under purifying selection. Our findings give insight into the origin and expansion of the FLA gene family and help us understand their functions during the process of evolution.


Depth of insertion of transpedicular vertebral screws into human vertebrae: effect upon screw-vertebra interface strength.
Improvement in the strength of the transpedicular screw-vertebra interface by increasing the depth of screw insertion may provide improved performance of spinal implants using such screws. Within human cadaveric vertebrae, we measured the failure strength of Vermont Spinal Fixator (VSF) screws under flexion or torsion loads and of Schanz screws under pull-out loads (along the screw axis). Comparisons between opposite pedicles of vertebral specimens were made at 50 vs. 80% and 80 vs. 100% of maximum available insertion depth. Mean failure strength of VSF screws at 50% depth was 75-77% (depending upon load type) of that at 80% depth; strength for screws at 100% ("to-cortex") depth was 124-154% of that at 80%. Reanalysis of the data from Lavaste shows, contrary to his conclusion, a 26% increase in strength from a 5-mm increase in screw depth of insertion. All these differences were significant (p less than 0.05) by the matched-pairs t test. Benefit from the increased strength of deeper screw placement must be balanced against possible increased operative risk. A "near-approach" x-ray view is suggested here to decrease that presumed operative risk.


[Experiences with an arterialized venous flap for intraoral defect reconstruction].
This clinical investigation should try out the suitability of arterialized venous forearm flaps for immediate reconstruction of intraoral defects after excision of an oral squamous cell carcinoma. In contrast to the free radial forearm flap there is no need for either sacrificing a peripheral artery or jeopardizing motor nerves. As the exact function of arterialized venous flaps is still unknown we had to take into account the possible loss of the flap. Therefore we used this flap in patients with small or medium sized defects only. All skin fat flaps were raised out of the right forearm using two different flap types. In 34 patient we used a flap with a superficial vein passing through (type I), in 5 patients we took a flap with two parallel proximal veins (type II). After the flap had been sutured into the intraoral defect, in flap type I the original distal end of the vein was anastomosed to an artery and the original proximal end to a vein. In flap type II there was no specific differentiation between the veins both. 18 (46.2%) of the flaps survived completely, 9 (23%) had superficial epithelial loss or some marginal necrosis and 12 (30.8%) became completely necrotic. Areas of partial loss developed slowly and formed stable granulation tissue. The flap donor sites were either closed primarily (n = 19) or were covered with split thickness skin graft (n = 20). There were no functional problems of the donor forearms. These results contrast with the high success rates achieved with orthodox free forearm flaps. Further research into venous flaps is essential.


Investigating the adhesion of water droplets at low temperatures.
Adhesion of droplets to solid surfaces at low temperatures is crucial for antifogging and antifreezing, etc. So far, most reports on adhesion measurements have been carried out in air-liquid-solid systems, but it remains difficult to precisely investigate the adhesion at low temperatures due to the uncontrollable condensation. On the basis of the liquid-liquid-solid system, a new method to measure the adhesion of water droplets at low temperatures was developed and employed. Moreover, the reported method could be viable in other liquid-liquid-solid systems with wider temperature window; thus, it will find applications in broad fields such as crude oil recovery, ore-dressing, and transfer printing.


Pulmonary oil micro-embolism (POME) syndrome: a review and summary of a large case series.
The use of steroid compounds formulated in oil for depot injection can be associated with acute pulmonary reactions characterized primarily by cough, but sometimes with other associated symptoms. The pathophysiology of these reactions remains unclear, although they are reported in the literature as 'POMEs' or pulmonary oil micro-embolism events. We report on a large case series and propose a case definition for these events. These events can raise significant concern even though they are often self-limited. It is hoped that clinicians will recognize these events more readily and be able to inform patients better, and that future reports and assessments can benefit from our proposed case definition.


Public psychiatry fellowships: a developing network of public-academic collaborations.
In response to the expanding public behavioral health care system, a network of 15 public-community psychiatry fellowships has developed over the past six years. The fellowship directors meet yearly to sustain and develop fellowships to recruit and retain psychiatrists in the public sector. This column describes five types of public-academic collaborations on which the fellowships are based. The collaborations focus on structural and fiscal arrangements; recruitment and retention; program evaluation, program research, and policy; primary care integration; and career development. These collaborations serve to train psychiatrists who will play a key role in the rapidly evolving health care system.


[Importance of a symptomatic visit in tuberculosis contacts--classification of secondary cases].
In order to improve the appropriateness of contact examinations, we investigated the characteristics of secondary tuberculosis cases. We included tuberculosis patients that were located in Kawasaki City between 2008 and 2011. The patients were considered as 2 separate groups: those with tuberculosis following contact with index cases registered in Kawasaki City and those with tuberculosis who were located in Kawasaki City. Secondary cases were defined as subjects who underwent a contact examination and developed active tuberculosis within 2 years from the last contact with the index case. The secondary cases were classified by diagnostic method, time, and sputum smear test results, followed by consideration of improvement measures. There were 1196 tuberculosis patients and 6157 subjects who underwent a contact examination. Of these, 35 patients developed tuberculosis secondary to index cases registered in Kawasaki City. These 35 cases were classified by diagnostic methods. Diagnosis occurred during a contact examination in 31 cases and during a symptomatic visit in 4 cases. There were 2 sputum smear-positive patients detected in a contact examination that was conducted > or = 6 months after contact. These 2 cases had a symptomatic cough, but did not visit a medical institution. There were 39 patients with secondary tuberculosis who were located in Kawasaki City. These 39 cases were also classified by diagnostic methods. Diagnosis occurred during a contact examination in 33 cases and during a symptomatic visit in 6 cases. There were 4 sputum smear-positive patients detected in a contact examination that was conducted > or = 6 months after contact. These 4 cases had a symptomatic cough, but did not visit a medical institution. Of the secondary cases, a sputum smear-positive state was detected in some of the patients at the time of a contact examination that was conducted > or = 6 months after contact. However, secondary cases should be discovered at a sputum smear-negative stage. Appropriate education regarding the importance of a medical visit at the onset of symptoms could decrease the number of patients that are identified in the sputum smear-positive state during a contact examination that occurs at least 6 months after contact.


A simple micromethod for collagen and total protein determination in formalin-fixed paraffin-embedded sections.
A simple, sensitive, and quantitative procedure is described for the measurement of collagen and protein content in tissue sections prepared from formalin-fixed paraffin-embedded samples. The method can detect as little as 5.7 micrograms of collagen per mg of protein. It is based on the selective binding of Sirius red F3BA and Fast green FCF to collagen and noncollagenous components, respectively, when the sections are stained with both dyes dissolved in aqueous saturated picric acid. Both dyes are eluted readily and simultaneously with NaOH-methanol and the absorbances obtained at 540 and 605 nm can be used to determine the amount of collagen and protein. The color equivalence of each dye was determined after destaining the sections and measuring the collagen content by hydroxyproline analysis and the amount of protein by the micro-Kjeldahl procedure. When several sections prepared from five rat tissues were analyzed first by the dye binding method and then by the chemical procedure, comparable results were obtained. This method could be of use in measuring collagen in tissue specimens and could be helpful in assessing the degree of fibrosis in tissue samples and in evaluating the effects of antifibrogenic drugs currently in use.


Association mapping and candidate genes for physiological non-destructive traits: Chlorophyll content, canopy temperature, and specific leaf area under normal and saline conditions in wheat.
Wheat plants experience substantial physiological adaptation when exposed to salt stress. Identifying such physiological mechanisms and their genetic control is especially important to improve its salt tolerance. In this study, leaf chlorophyll content (CC), leaf canopy temperature (CT), and specific leaf area (SLA) were scored in a set of 153 (103 having the best genotypic data were used for GWAS analysis) highly diverse wheat genotypes under control and salt stress. On average, CC and SLA decreased under salt stress, while the CT average was higher under salt stress compared to the control. CT was negatively and significantly correlated with CC under both conditions, while no correlation was found between SLA and CC and CT together. High genetic variation and broad-sense-heritability estimates were found among genotypes for all traits. The genome wide association study revealed important QTLs for CC under both conditions (10) and SLA under salt stress (four). These QTLs were located on chromosomes 1B, 2B, 2D, 3A, 3B, 5A, 5B, and 7B. All QTLs detected in this study had major effects with R2 extending from 20.20% to 30.90%. The analysis of gene annotation revealed three important candidate genes (TraesCS5A02G355900, TraesCS1B02G479100, and TraesCS2D02G509500). These genes are found to be involved in the response to salt stress in wheat with high expression levels under salt stress compared to control based on mining in data bases.


The Impact of Volume Overload on the Longitudinal Change of Adipose and Lean Tissue Mass in Incident Chinese Peritoneal Dialysis Patients.
Patients treated with peritoneal dialysis (PD) experience complex body composition changes that are not adequately reflected by traditional anthropometric parameters. While lean and adipose tissue mass can be readily assessed by bioimpedance spectroscopy (BIS), there is concern about the potential confounding effect of volume overload on these measurements. This study aimed to assess the influence of fluid status (by echocardiography) on body composition parameters measured by BIS and to describe the longitudinal changes in adipose and lean tissue mass. We conducted a prospective observational study in a tertiary hospital. Incident Chinese PD patients underwent baseline echocardiography and repeated BIS measurements at baseline and 12 months later. Among 101 PD patients, lean tissue index (LTI) or fat tissue index (FTI) was not associated with echocardiographic parameters that reflected left ventricular filling pressure (surrogate of volume status). Sixty-eight patients with repeated BIS had a significant increase in body weight and FTI, while LTI remained similar. Gains in fat mass were significantly associated with muscle wasting (beta = −0.71, p < 0.0001). Moreover, progressive fluid accumulation independently predicted decrease in FTI (beta = −0.35, p < 0.0001) but not LTI. Body composition assessments by BIS were not affected by fluid status and should be considered as part of comprehensive nutrition assessment in PD patients.


A Subsequent Human Neural Progenitor Transplant into the Degenerate Retina Does Not Compromise Initial Graft Survival or Therapeutic Efficacy.
Stem and progenitor cell transplantation provides a promising clinical application for treating degenerative retinal diseases, including age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Our previous studies have shown that a single subretinal injection of human cortical-derived neural progenitor cells (hNPCctx) into cyclosporine-treated Royal College of Surgeons (RCS) rats preserved both photoreceptors and visual function. However, it is still unknown whether nonautologous progenitor cell readministration for sustained vision is efficacious and safe in terms of the initial graft initiating an immune response to a subsequent graft. A cell suspension containing 3×104 hNPCctx into one eye of cyclosporine-treated RCS rats at postnatal day 21 (P21), followed by a second transplantation at P95 into the previously untreated fellow eye. hNPCctx delayed photoreceptor degeneration and preserved visual function, as measured by electroretinography (ERG), optokinetic response (OKR), and luminance threshold recordings (LTRs). Visual function and photoreceptors of the initially treated eye were still preserved 6 weeks after hNPCctx were injected into the second eye. Antibodies against T-cell markers showed that CD3, CD4, and CD8 T cells were not detected at P90 and P140 in most cases. No detectable level of anti-nestin antibody was found in serum by enzyme-linked immunosorbent assay (ELISA). This xenograft study with cyclosporine-treated animals demonstrates that readministration of hNPCctx into the fellow eye did not induce anti-graft immune responses or lower therapeutic efficacy of hNPCctx in preserving vision. Thus, readministration of progenitor cells to sustain long-term efficacy may be an option for long-term therapies of retinal degeneration. Redosing neural progenitors do not affect the efficacy of the initial grafts in protecting vision or induce unwanted immune responses.


The validity of the depression rating scales in discriminating between citalopram and placebo in depression recurrence in the maintenance therapy of elderly unipolar patients with major depression.
The World Federation of Societies of Biological Psychiatry guidelines for treatment of unipolar major depression has recommended three depression rating scales for evaluating outcome: The Hamilton Depression Rating Scale (HAM-D), the Montgomery-Asberg Depression Rating Scale (MADRS), and the Bech-Rafaelsen Melancholia Scale (MES). In this study we evaluated the ability of these scales to differentiate between citalopram and placebo in the recurrence prevention of unipolar depression. The study is a psychometric reexamination of a trial on the efficacy of citalopram versus placebo in the maintenance therapy of elderly patients with unipolar depression. Internal validity (the Cronbach coefficient alpha, the Loevinger coefficient of homogeneity, and factor analysis) of the three scales has been examined to evaluate their unidimensionality. In the outcome analysis for depression recurrence, the conventional cutoff scores of the three scales are used. In total, 60 patients received citalopram and 61 patients received placebo in the maintenance phase of 48 weeks. The results showed that the internal validity was higher for MES and MADRS than for HAM-D. Using the MADRS, 67.2 % of the patients on placebo and 31.6 % of the patients on citalopram developed a depression recurrence (ratio 2.12); using HAM-D17, 42.6 % on placebo and 13.3 % on citalopram developed a depression recurrence (ratio 3.20); and using the MES, 34.4 % on placebo and 11.7 % on citalopram developed a depression recurrence (ratio 2.94). The conventional cutoff scores of HAM-D17 and MES for depression recurrence indicated a ratio between citalopram and placebo of around 3, while the conventional cutoff scores of MADRS for depression recurrence indicated a ratio of only around 2. In future trials on the recurrence prevention of unipolar depression, a cutoff score of 25 rather than 22 on the MADRS is recommended.


Idealization in evolutionary developmental investigation: a tension between phenotypic plasticity and normal stages.
Idealization is a reasoning strategy that biologists use to describe, model and explain that purposefully departs from features known to be present in nature. Similar to other strategies of scientific reasoning, idealization combines distinctive strengths alongside of latent weaknesses. The study of ontogeny in model organisms is usually executed by establishing a set of normal stages for embryonic development, which enables researchers in different laboratory contexts to have standardized comparisons of experimental results. Normal stages are a form of idealization because they intentionally ignore known variation in development, including variation associated with phenotypic plasticity (e.g. via strict control of environmental variables). This is a tension between the phenomenon of plasticity and the practice of staging that has consequences for evolutionary developmental investigation because variation is conceptually removed as a part of rendering model organisms experimentally tractable. Two compensatory tactics for mitigating these consequences are discussed: employing a diversity of model organisms and adopting alternative periodizations.


Endoscopic repair of supraglottic laryngeal clefts.
We describe the technique of endoscopic diagnosis and endoscopic surgical repair used in the management of supraglottic interarytenoid laryngeal clefts in 11 children seen between 1981 and 1988 at the Hospital for Sick Children, London, England. Six of the children had primary type I clefts that required endoscopic repair. The symptoms included inspiratory stridor, choking during eating, and aspiration. Five of the children had previous transcervical repair of type II clefts that had partial breakdown in the interarytenoid area causing symptoms of aspiration, which required secondary repair endoscopically. All the patients had successful microlaryngoscopic closure; in two children, however, the breakdown of the repair necessitated repeated endoscopic correction. The only complication occurred in a case of postoperative supraglottitis, which was successfully managed with intubation and antibiotics. We conclude that endoscopic repair is a useful and reliable technique and an elegant alternative to the open transcervical approach for the closure of supraglottic laryngeal clefts.


Expression of B2-type cyclin-dependent kinase is controlled by protein degradation in Arabidopsis thaliana.
The eukaryotic cell cycle is controlled by cyclin-dependent kinases (CDKs). Plants possess six types of CDK, among which the B-type CDK (CDKB) is expressed specifically from the late S- to the M-phase. We demonstrate that the expression of Arabidopsis CDKB2 is under the control of the protein degradation machinery. beta-Glucuronidase fused to a putative PEST motif of CDKB2 was unstable in tobacco Bright Yellow-2 cells and Arabidopsis plants, and its degradation was arrested by the proteasome inhibitor MG132. We propose that the abundance of CDKB2 protein is regulated not only at the transcriptional level, but also through proteasome-mediated protein degradation.


Preprosthetic periodontal surgery in the proximal area with modification of the col area: results following the reestablishment of the contact point.
Anatomic characteristics of interproximal areas are dependent on the anatomy, position, and proximal contact of adjacent teeth. The objective of this study was to investigate the influence of the reestablishment of the interproximal contact following the restorative alveolar interface (RAI) procedure on the interproximal gingival COL and formation of the interdental gingival papilla. Six mongrel dogs received bilateral apically positioned flaps, crown lengthening, and the RAI procedure on the maxillary fourth bicuspid and first molar. After 2 weeks, in a randomized manner, one side was prepared to receive metallic crowns and the opposite side remained as the control. The crowns were cemented at the 4-week postoperative period, and the dogs were sacrificed after another 4 weeks, totaling a period of 4 weeks with the full crowns in position and a total of 8 postoperative weeks. Histologic specimens were stained with hematoxylin and eosin and Mallory dyes. Sections 6 micro m thick were obtained in a bucco-lingual plane allowing ample visualization of the interproximal area. Clinical measurements revealed that, in the restored sides, four animals had complete fill of the interdental spaces with gingival papilla, whereas the other two dogs had a distance from the contact point to the tip of papilla varying from 0.02 to 0.021 mm. In the control group, papillae were totally reepithelialized with keratinized epithelium and a convex form. The epithelium completely covered the connective tissue and showed both epithelial projections and surface desquamation. On the test group, despite the presence of the prosthesis, the COL morphology modified by preprosthetic surgery was not altered, presenting a convex papilla with a triangular form and with a keratinized epithelium. Additional histologic characteristics were the same as found in the control group. Based on the results of this study, the reestablishment of the contact point does not revert what was obtained with the RAI procedure; the interproximal tissues remain convex and keratinized.


Enclaves of genetic diversity resisted Inca impacts on population history.
The Inca Empire is claimed to have driven massive population movements in western South America, and to have spread Quechua, the most widely-spoken language family of the indigenous Americas. A test-case is the Chachapoyas region of northern Peru, reported as a focal point of Inca population displacements. Chachapoyas also spans the environmental, cultural and demographic divides between Amazonia and the Andes, and stands along the lowest-altitude corridor from the rainforest to the Pacific coast. Following a sampling strategy informed by linguistic data, we collected 119 samples, analysed for full mtDNA genomes and Y-chromosome STRs. We report a high indigenous component, which stands apart from the network of intense genetic exchange in the core central zone of Andean civilization, and is also distinct from neighbouring populations. This unique genetic profile challenges the routine assumption of large-scale population relocations by the Incas. Furthermore, speakers of Chachapoyas Quechua are found to share no particular genetic similarity or gene-flow with Quechua speakers elsewhere, suggesting that here the language spread primarily by cultural diffusion, not migration. Our results demonstrate how population genetics, when fully guided by the archaeological, historical and linguistic records, can inform multiple disciplines within anthropology.


Implications of sample treatment on characterization of riverine dissolved organic matter.
High-resolution mass spectrometry techniques are widely used in the environmental sciences to characterize natural organic matter and, when utilizing these instruments, researchers must make multiple decisions regarding sample pre-treatment and the instrument ionization mode. To identify how these choices alter organic matter characterization and resulting conclusions, we analyzed a collection of 17 riverine samples from East River, CO (USA) under four PPL-based Solid Phase Extraction (SPE) treatment and electrospray ionization polarity (e.g., positive and negative) combinations: SPE (+), SPE (-), non-SPE (-), and non-SPE (+). The greatest number of formula assignments were achieved with SPE-treated samples due to the removal of compounds that could interfere with ionization. Furthermore, the SPE (-) treatment captured the most formulas across the widest chemical compound diversity. In addition to a reduced number of assigned formulas, the non-SPE datasets resulted in altered thermodynamic interpretations that could cascade into incomplete assumptions about the availability of organic matter pools for heterotrophic microbial respiration. Thus, we infer that the SPE (-) treatment is the best single method for characterizing environmental organic matter pools unless the focus is on lipid-like compounds, in which case we recommend a combination of SPE (-) and SPE (+) to adequately characterize these molecules.


Hybrid Attention Network for Epileptic EEG Classification.
Automatic seizure detection from electroencephalography (EEG) based on deep learning has been significantly improved. However, existing works have not adequately excavate the spatial-temporal information between EEG channels. Besides, most works mainly focus on patient-specific scenarios while cross-patient seizure detection is more challenging and meaningful. Regarding the above problems, we propose a hybrid attention network (HAN) for automatic seizure detection. Specifically, the graph attention network (GAT) extracts spatial features at the front end, and Transformer gets time features as the back end. HAN leverages the attention mechanism and fully extracts the spatial-temporal correlation of EEG signals. The focal loss function is introduced to HAN to deal with the imbalance of the dataset accompanied by seizure detection based on EEG. Both patient-specific and patient-independent experiments are carried out on the public CHB-MIT database. Experimental results demonstrate the efficacy of HAN in both experimental settings.


Exciton dispersion and exciton-phonon interaction in solids by time-dependent density functional theory.
Understanding, predicting, and ultimately controlling exciton band structure and exciton dynamics are central to diverse chemical and materials problems. Here, we have developed a first-principles method to determine exciton dispersion and exciton-phonon interaction in semiconducting and insulating solids based on time-dependent density functional theory. The first-principles method is formulated in planewave bases and pseudopotentials and can be used to compute exciton band structures, exciton charge density, ionic forces, the non-adiabatic coupling matrix between excitonic states, and the exciton-phonon coupling matrix. Based on the spinor formulation, the method enables self-consistent noncollinear calculations to capture spin-orbital coupling. Hybrid exchange-correlation functionals are incorporated to deal with long-range electron-hole interactions in solids. A sub-Hilbert space approximation is introduced to reduce the computational cost without loss of accuracy. For validations, we have applied the method to compute the exciton band structure and exciton-phonon coupling strength in transition metal dichalcogenide monolayers; both agree very well with the previous GW-Bethe-Salpeter equation and experimental results. This development paves the way for accurate determinations of exciton dynamics in a wide range of solid-state materials.


Transcriptional switches: chemical approaches to gene regulation.
Given the role of transcriptional misregulation in the pathogenesis of human disease, there is enormous interest in the development of molecules that exogenously control transcription in a defined manner. The past decade has seen many exciting advancements in the identification of molecules that mimic or inhibit the interactions between natural transcriptional activators and their binding partners. In this minireview, we focus on four activator.target protein complexes, highlighting recent advances as well as challenges in the field.


[Current practices of transition from pediatric to adult health care for patients with neurological disease: promote the cooperation between child and adult neurologists].
The Special Committee for Measures Against Transition from Pediatric to Adult Health Care of the Japanese Society of Neurology, which consists of child and adult neurologists, started to tackle the issues of pediatric to adult health care transition for patients with neurological disease in July 2020. The Committee held a workshop with a theme of "cooperation between child and adult neurologists," which is a critical issue in the pediatric to adult health care transition. To solve the many problems in the pediatric to adult health care transition, it is crucial that child and adult neurologists and primary care physicians cooperate on the following issues: preparing child neurologists for the transition, encouraging adult neurologists to study child neurology, promoting the formation of multidisciplinary teams, improving the medical system and medical fees, appealing to governmental agencies for issues of community health care and welfare services.


Long-term outcome following repair of acute type A aortic dissection after previous cardiac surgery.
We evaluated the outcome after repair for acute spontaneous type A aortic dissection in patients with previous cardiac surgery. From January 2000 to December 2009, 114 patients underwent emergency repair for acute spontaneous type A dissection at Southampton University Hospital. Eleven (median age 64 years; range 36-83 years; two females) patients (9.8%) had undergone previous cardiac surgery and were included in this study. Aortic root replacement was performed in three patients (27%), aortic arch replacement in four patients (36%) and two patients (18%) required aortic valve re-suspension. The elephant trunk operation was performed in two patients (18%). There were two hospital deaths (18%). Two patients (18%) suffered a stroke, two needed re-opening for bleeding (18%) and two patients (18%) required haemofiltration postoperatively. Median length of hospital stay was 16 days (range 6-34 days). Actuarial survival at five and eight years for redo compared to first-time surgery was 68±3.63% vs. 81±5.34% and 51±3.8% vs. 61±5.4%, respectively (P=0.365). In conclusion, acute type A aortic dissection repair in patients with previous cardiac surgery has an acceptable mortality and comparable long-term outcome to first-time surgery.


Organic electrochemical transistor arrays for real-time mapping of evoked neurotransmitter release in vivo.
Though neurotransmitters are essential elements in neuronal signal transduction, techniques for in vivo analysis are still limited. Here, we describe an organic electrochemical transistor array (OECT-array) technique for monitoring catecholamine neurotransmitters (CA-NTs) in rat brains. The OECT-array is an active sensor with intrinsic amplification capability, allowing real-time and direct readout of transient CA-NT release with a sensitivity of nanomolar range and a temporal resolution of several milliseconds. The device has a working voltage lower than half of that typically used in a prevalent cyclic voltammetry measurement, and operates continuously in vivo for hours without significant signal drift, which is inaccessible for existing methods. With the OECT-array, we demonstrate simultaneous mapping of evoked dopamine release at multiple striatal brain regions in different physiological scenarios, and reveal a complex cross-talk between the mesolimbic and the nigrostriatal pathways, which is heterogeneously affected by the reciprocal innervation between ventral tegmental area and substantia nigra pars compacta.


Anticholinesterase drugs stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.
We performed this study to determine the effects of Rho-kinase inhibitors, Y-27632 and fasudil, on the anticholinesterase (anti-ChE)-induced contractile and phosphatidylinositol responses of the rat trachea. In vitro measurements of isometric tension and [3H] inositol monophosphate (IP1) that was formed were conducted by using rat tracheal rings or slices. Neostigmine- and pyridostigmine-induced contractions were almost completely inhibited by Y-27632 and fasudil at 30 microM each, whereas acetylcholine-induced contraction was inhibited incompletely, i.e., by 56% by Y-27632 and by 51% by fasudil, at 100 microM for each, respectively. The inhibitory effects of fasudil on neostigmine- and acetylcholine-induced contractions were completely reversed by calyculin-A, a myosin phosphatase inhibitor. Neostigmine-induced IP1 accumulation was attenuated by fasudil at 100 microM. The results suggest that anti-ChEs cause airway smooth muscle contraction, in part, through activation of the Rho-kinase pathway.


Making instruction and assessment responsive to diverse students' progress: group-administered dynamic assessment in teaching mathematics.
This study entailed a 3 (instructional intervention) × 2 (assessment-type) between-subjects experimental design employing a pretest-intervention-posttest methodology. The instructional interventions were administered between subjects in three conditions: (a) dynamic instruction, (b) triarchic or theory of successful intelligence-control instruction, and (c) standard-control instruction. The assessment-type consisted between subjects of either (a) a group-administered dynamic posttest or (b) the same group-administered posttest interspersed with a control filler activity. Performance in different mathematics content areas taught in fourth grade was investigated. In total, 1,332 students and 63 classroom teachers in 24 schools across six school districts participated in the study. The results indicate the advantages of using dynamic instruction and assessment in regular classrooms while teaching mathematics, especially when the student body is highly ethnically diverse.


Photolysis properties of merocyanine dye LB films by various time of UV irradiation.
We fabricated the merocyanine dye LB films with arachidic acid (MD LB films). We compared absorption peak of before and after added Cd2+. The optical absorption peak of the MD LB films was shifted to 610 nm at 535 nm, when Cd2+ ions were added. We also investigated the optical absorption peak of the LB films by various time at 365 nm UV. We confirmed J-aggregation and photolysis properties. This is that studied the application possibility of the switching device and the nonvolatile memory.


SPARC production by bone marrow-derived cells contributes to myocardial fibrosis in pressure overload.
In human heart failure and in murine hearts with left-ventricular pressure overload (LVPO), increases in fibrosis are associated with increases in myocardial stiffness. Secreted protein acidic and rich in cysteine (SPARC) is shown to be necessary for both cardiac fibrosis and increases in myocardial stiffness in response to LVPO; however, cellular sources of cardiac SPARC are incompletely defined. Irradiation and bone marrow transfer were undertaken to test the hypothesis that SPARC expression by bone marrow-derived cells is an important mediator of fibrosis in LVPO. In recipient SPARC-null mice transplanted with donor wild-type (WT) bone marrow and subjected to LVPO, levels of fibrosis similar to that of WT mice were found despite the lack of SPARC expression by resident cells. In recipient WT mice with donor SPARC-null bone marrow, significantly less fibrosis versus that of WT mice was found despite the expression of SPARC by resident cells. Increases in myocardial stiffness followed a similar pattern to that of collagen deposition. Myocardial macrophages were significantly reduced in SPARC-null mice with LVPO versus that of WT mice. Recipient SPARC-null mice transplanted with donor WT bone marrow exhibited an increase in cardiac macrophages versus that of SPARC-null LVPO and donor WT mice with recipient SPARC-null bone marrow. Expression of vascular cellular adhesion molecule (VCAM), a previously identified binding partner of SPARC, was assessed in all groups and with the exception of WT mice, increases in VCAM immunoreactivity with LVPO were observed. However, no differences in VCAM expression between bone marrow transplant groups were noted. In conclusion, SPARC expression by bone marrow-derived cells was critical for fibrotic deposition of collagen and influenced the expansion of myocardial macrophages in response to LVPO.NEW & NOTEWORTHY Myocardial fibrosis and the resultant increases in LV and myocardial stiffness represent pivotal consequences of chronic pressure overload (PO). In this study, a murine model of cardiac fibrosis induced by PO was used to demonstrate a critical function of SPARC in bone marrow-derived cells that drives cardiac fibrosis and increases in cardiac macrophages.


Elevated Cerebrospinal Fluid Proteins and Albumin Determine a Poor Prognosis for Spinal Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a heterogeneous disease, both in its onset phenotype and in its rate of progression. The aim of this study was to establish whether the dysfunction of the blood-brain barrier (BBB) and blood-spinal cord barrier (BSCB) measured through cerebrospinal fluid (CSF) proteins and the albumin-quotient (QAlb) are related to the speed of disease progression. An amount of 246 patients diagnosed with ALS were included. CSF and serum samples were determined biochemically for different parameters. Survival analysis based on phenotype shows higher probability of death for bulbar phenotype compared to spinal phenotype (p-value: 0.0006). For the effect of CSF proteins, data shows an increased risk of death for spinal ALS patients as the value of CSF proteins increases. The same model replicated for CSF albumin yielded similar results. Statistical models determined that the lowest cut-off value for CSF proteins able to differentiate patients with a good prognosis and worse prognosis corresponds to CSF proteins ≥ 0.5 g/L (p-value: 0.0189). For the CSF albumin, the QAlb ≥0.65 is associated with elevated probability of death (p-value: 0.0073). High levels of QAlb are a bad prognostic indicator for the spinal phenotype, in addition to high CSF proteins levels that also act as a marker of poor prognosis.


A single-institution retrospective analysis of pathologically determined malignant transformation in IDH mutant glioma patients.
Lower-grade IDH mutant glioma patients frequently undergo malignant transformation (MT), with apparent worse prognosis. Many studies examine MT in mixed IDH status cohorts and define MT using imaging, not histopathology. Our study examines the timing, predictors, and prognostic implications of pathologically determined MT in a large, exclusively IDH mutant cohort. We identified 193 IDH mutant lower-grade glioma patients at UCLA who received multiple surgeries. We examined the outcomes of pathologically determined MT patients. Time to MT is longer in grade 2 oligodendroglioma (G2 Oligo) than in grade 2 astrocytoma (G2 Astro) (HR = 0.46, P = .0007). The grade 3 astrocytoma (G3 Astro) to grade 4 astrocytoma (G4 Astro) interval is shorter in stepwise MT (G2 to G3 to G4 Astro) patients than in initial G3 Astro patients (P = .03). Novel contrast enhancement had 65% positive predictivity, 67% negative predictivity, 75% sensitivity, and 55% specificity in indicating pathologically defined MT. In G2 Astro, initial gross total resection delayed MT (HR = 0.50, P = .02) and predicted better overall survival (OS) (HR = 0.34, P = .009). In G2 Oligo, spontaneous MT occurred earlier than treated MT (HR = 11.43, P = .0002), but treatment did not predict improved OS (P = .8). MT patients (n = 126) exhibited worse OS than non-MT patients (n = 67) in All (HR = 2.54, P = .0009) and G2 Astro (HR = 4.26, P = .02). Our study expands the understanding of MT to improve IDH mutant lower-grade glioma management.


Circulating hematopoietic progenitor cells in first trimester fetal blood.
The yolk sac and aorto-gonad-mesonephros region are well recognized as the principal sites of hematopoiesis in the developing embryo, and the liver is the principal site of hematopoiesis in the fetus. However, little is known about circulating hematopoietic stem and progenitor cells in early fetal life. We investigated the number and characteristics of circulating progenitors in first trimester blood of 64 human fetuses (median gestational age, 10(+4) weeks; range, 7(+6)-13(+6) weeks). CD34+ cells accounted for 5.1 +/- 1.0% of CD45+ cells in first trimester blood, which is significantly more than in term cord blood (0.4 +/- 0.03%; P =.0015). However, the concentration of CD34+ cells (6.6 +/- 2.4 x 10(4)/mL) was similar to that in term cord blood (5.6 +/- 3.9 x 10(4)/mL). The total number of progenitors cultured from unsorted mononuclear cells (MNCs) in first trimester blood was 19.2 +/- 2.1 x 10(3)/mL, which is similar to that in term cord blood (26.4 +/- 5.6 x 10(3)/mL). All lineages were seen: colony-forming unit-GEMM (CFU-GEMM), CFU-GM, BFU-e, BFU-MK, and CFU-MK. Clonogenic assays of CD34+ cells purified from first trimester samples produced mainly two lineages: BFU-e (39.0 +/- 9.6 x 10(3)/mL CD34+ cells) and CFU-GEMM (22.6 +/- 4.7 x 10(3)/mL CD34+ cells). Short-term liquid culture of first trimester blood MNCs in SCF + IL-3 + Flt-3 (stem cell factor + interleukin-3 + Flt-3) increased, by 7-fold, the numbers of CFU-GEMM and induced a dramatic increase in BFU-e (65.6 +/- 12.1-fold). These data show that significant numbers of committed and multipotent progenitors with capacity for expansion circulate in first trimester fetal blood and can be CD34 selected. These cells should be suitable targets for gene transfer and stem cell transplantation and, because fetal hematopoietic progenitors have been demonstrated in the maternal circulation from early gestation, may also be manipulated for noninvasive prenatal diagnosis of major genetic disorders. (Blood. 2000;95:1967-1972)


Antibiotic prescribing patterns at children's outpatient departments of primary care institutions in Southwest China.
Inappropriate use of antibiotics in children is common in many countries. The purpose of the study was to explore patterns of antibiotic prescribing in children's outpatient clinics in primary care institutions in a province of southwest China. We obtained electronic prescription data from 75 primary care institutions in Guizhou province in 2020. The classification of incorrect spectrum of antibiotics, unnecessary use and combined use of antibiotics was based on the Guiding Principle of Clinical Use of Antibiotics (2015, China) and guidelines from the USA Centers for Disease Control and Prevention. Potential risk factors for inappropriate use of antibiotics were identified using bivariate analyses. The generalized estimation equation was used to identify independent predictors of inappropriate use of antibiotics. A total of 158,267 antibiotic prescriptions were retrieved. Acute upper respiratory tract infections were the most common diseases, accounting for 74.9% of all prescriptions. The main antibiotic group used was penicillins (63.7%), followed by cephalosporins (18.8%). Of 137,284 visits, 18.3% of antibiotic prescriptions were appropriate and the percentage of unnecessary use, incorrect spectrum of antibiotics and combined use of antibiotics was 76.9, 2.4 and 2.4%, respectively. Physicians with lower professional titles and more than 40 years of work duration were relatively more likely to prescribe inappropriate antibiotics. The inappropriate use of antibiotics in children is still prominent in primary care institutions of southwest China. The education and training of physicians and caregivers in these institutions should be strengthened.


How closely is Helicobacter pylori infection related to gastroduodenal lesions?
Various studies have indicated a relationship between Helicobacter pylori infection and upper gastrointestinal lesions, but this relationship needs to be assessed in individuals not seeking medical treatment for complaints. We screened community residents for H. pylori infection and upper gastrointestinal lesions during an annual mass health examination aiming to determine relationships between infection and lesions. In 932 examinees we performed a 13C-urea breath test for H. pylori infection, and assessed degree of gastric atrophy by measuring pepsinogen I and II in serum. In 738 subjects we also performed upper gastrointestinal radiography with or without endoscopy. Prevalence of H. pylori infection increased with age, and the ratio of serum pepsinogen I to II decreased with age. Prevalence of H. pylori infection did not differ significantly between subjects with and without radiographically or endoscopically evident lesions. Of H. pylori-positive subjects with peptic ulcer, 73.2% had no recurrence of ulcer despite absence of medical treatment. Prolonged H. pylori infection was associated with atrophy of the gastric mucosa, but little relationship was evident between H. pylori infection and development or recurrence of peptic ulcer.


Conformational behaviour, hydrogen bond competition and intramolecular dynamics in vanillin derivatives: acetovanillone and 6-hydroxy-3-methoxyacetophenone.
The conformational landscape of the structural isomers acetovanillone (apocynin, AV) and 6-hydroxy-3-methoxyacetophenone (HMAP) has been investigated in a supersonic jet using Fourier transform microwave spectroscopy. Two conformers have been detected in the jet-cooled expansion for each molecule (s-cis and s-trans in AV; s-trans and a-trans for HMAP), differing in the relative orientation of the acetyl and methoxy groups. Both molecules are stabilized by O-H···O or O-H···O=C hydroxyl intramolecular hydrogen bonds, either constraining the local conformations of the methoxy group in AV, or that of the acetyl group in HMAP. Internal rotation splittings have been observed in both conformers of each molecule, originated by the acetyl group, that yield information on the influence of the intramolecular hydrogen bonds on the methyl torsion. The similar internal rotation barriers in both molecules (6.6 and 7.4 kJ mol(-1) in AV; 7.3 and 7.0 kJ mol(-1) in HMAP) suggest that the acetyl torsion is only slightly affected by intramolecular hydrogen bonding. The absence of torsional tunnellings due to the methoxy group indicates torsional barriers above 10.2 and 8.9 kJ mol(-1) for AV conformers, 10.1 and 10.4 kJ mol(-1) for HMAP. Conformational ratios and relative free energies have been estimated from relative intensity measurements of the spectral lines. Ab initio (MP2) and density functional calculations using the recent M05-2X empirical functional have been used to aid the experimental work in describing the structures, internal rotation barriers and isomerization potentials.


Association of Streptococcus bovis presence in colonic content with advanced colonic lesion.
To prospectively examine the association between presence of Streptococcus bovis (S. bovis) in colonic suction fluid and the endoscopic findings on colonoscopy. From May 2012 to March 2013, 203 consecutive patients who underwent colonoscopy for any reason were enrolled in the study. Exclusion criteria included: antibiotic use in the previous month, age younger than 18 years, and inadequate preparation for colonoscopy. The colonoscopy was performed for the total length of the colon or to the occluding tumor. The endoscopic findings were registered. Samples were obtained proximal to the colonoscopic part of the suction tube from each patient and sent to the clinical microbiology laboratory for isolation and identification of S. bovis. Samples were incubated in enrichment media with addition of antibiotic disks for inhibition of growth of Gram-negative rods. The samples were seeded on differential growth media; suspected positive colonies were isolated and identified with Gram staining, catalase, and pyrrolidonyl arylamidase tests, and further identified using a VITEK2 system. Statistical analyses were performed using the Student's t and χ(2) tests. Of the 203 patients recruited, 49 (24%) patients were found to be S. bovis carriers; of them, the endoscopic findings included: 17 (34.7%) cases with malignant tumors, 11 (22.4%) with large polyps, 5 (10.2%) with medium-sized polyps, 6 (12.2%) with small polyps, 4 (8.1%) with colitis, and 6 (12.2%) normal colonoscopies. Of 154 patients found negative for S. bovis, the endoscopic findings included: none with malignant tumors, 9 (5.8%) cases with large polyps, 11 (7.1%) with medium-sized polyps, 26 (16.9%) with small polyps, 7 (4.5%) with colitis, and 101 (65.6%) normal colonoscopies. S. bovis (Gram-positive coccus) is considered part of the normal intestinal flora. There is an association between S. bovis bacteremia and colonic neoplasia. It is not well understood whether the bacterium has a pathogenetic role in the development of neoplasia or constitutes an epiphenomenon of colorectal neoplasms. There was a clear relationship between positivity for S. bovis in colonic suction fluid and findings of malignant tumors and large polyps in the colon. There is an association between S. bovis bacteremia and malignant colonic lesions; this should prompt for development of a reliable screening method for advanced colonic lesions.


[The effects of carotenoids on the proliferation of human breast cancer cell and gene expression of bcl-2].
To investigate the effects of various carotenoids on the proliferation, cell cycle, apoptosis and expression of bcl-2 gene in breast cancer cell MCF-7. Time and dose effects of individual carotenoids were detected using the MTT assay. The effects of individual carotenoids on cell cycle and the apoptosis were observed by flow cytometry. The expression of bcl-2 mRNA gene was detected using the RT-PCR method. All 4 carotenoids tested inhibited the proliferation of MCF-7 cell line, but with different potencies. beta-carotene and lycopene were the most active inhibitors (inhibition rate 88.2% and 87.8%, respectively) followed by zeaxanthin and astaxanthin. All 4 carotenoids did not induce cell apoptosis. Cell cycle progression was blocked at G(2)/M phase with 60 micromol/L lycopene and at G(0)/G(1) phase with 60 micromol/L zeaxanthin dipalmitate. Carotenoids down regulated bcl-2 gene expression. Carotenoids could inhibit the proliferation of human beast cancer MCF-7 cell line in vitro and the action of carotenoids may be worked through different pathways.


A new ELISA for quantification of brassinosteroids in plants.
Starting from (22R,23R)-2α,3α,22,23,26-pentahydroxy-5α-cholestan-6-one 26-hemisuccinate, conjugates of 28-norcastasterone with horse radish peroxidase and bovine serum albumin were prepared. The latter conjugate was injected into rabbits; produced polyclonal antibodies were used to quantitate 6-keto-brassinosteroids. The newly developed analytical system was used in combination with two other immunoenzymatic assays for brassinosteroids to determine individual compounds of this series. In addition, a direct method of brassinosteroid analysis was proposed. It has the advantage of requiring no sample pretreatment steps such as extraction with organic solvents and chromatography.


Drug transport across the blood-testis barrier.
The blood-testis barrier transfers nutrients to spermatogenic tubules to ensure the normal physiological function of the testes. It also restricts the "entry and exit" of biological macromolecules in the testicular lumen and provides a unique microenvironment for spermatogenesis. This makes the testes a safe place for some viruses and tumors, as immune factors cannot function and drugs fail to reach therapeutic concentrations in the testes. This review aimed to describe the factors regulating the structure and physiological function of the blood-testis barrier. By understanding therapeutic mechanisms of action, drugs can be developed to function in the testicles.


Cross-sectional imaging of paragangliomas of the aortic body and other thoracic branchiomeric paraganglia.
Our purpose was to show the CT and MRI findings of paragangliomas of the aortic body and the great vessels of the mediastinum. Paragangliomas of the aortic body and the great vessels have a characteristic imaging appearance. They originate from known sites of the branchiomeric paraganglia such as the aortic body. Knowledge of the location of the aortic body and other paraganglia combined with an appreciation of the how these tumors grow and displace neighboring structures will suggest a potential diagnosis of mediastinal paraganglioma.


Kennel enrichment: exercise and socialization of dogs.
In the last 50 years, there has been a growing need for storage and management systems for the production and maintenance of large numbers of dogs. Unwanted dogs and strays, detained in kennels, stay for various lengths of time. Large kennels also produce dogs for sale as companion animals, for the service dog industry (police and guide dogs), for biomedical research, and for use by dog food companies. Across the United States, literally tens of thousands of dogs are born in kennels and spend their lives in kennels. The laboratory dog, the kennel dog, the service dog, and the companion dog are in an evolutionary transition period, accompanied by concomitant adaptation to stresses signaled by a high frequency of genetic disease and behavioral abnormalities. For kennel enrichment programs, such as socialization and exercise, the modern kenneled dog is a genetically moving target. Specific recommendations apply neither to all breeds nor to the variations within a single breed.


Apelin-13 and Asprosin in Adolescents with Anorexia Nervosa and Their Association with Psychometric and Metabolic Variables.
Anorexia nervosa (AN) is a widespread, metabo-psychiatric disorder with high relapse rates, comorbidity, and mortality. Many regulatory proteins and neurohormones studied to date play essential roles in the etiopathogenesis of eating disorders and the maintenance of psychopathological symptoms. Nevertheless, the regulatory and pathophysiological mechanisms of AN are still poorly understood. In the presented study, the plasma levels of apelin-13 (APE-13) and asprosin (ASP), as well as carbohydrate metabolism parameters and psychometric parameters, were evaluated in low-weight adolescent female patients with AN (AN1), after partial weight normalization (AN2) and in an age-matched healthy control group (CG) were evaluated. APE-13 levels were higher in the AN1 group than in the post-realimentation and the CG group. APE-13 levels were independent of insulin and glucose levels. Plasma ASP levels increased with increasing body weight in patients with AN, correlating with the severity of eating disorder symptoms in emaciation. The presented data suggest that APE-13 and ASP may be AN's biomarkers-regulation of eating behavior by APE-13 and ASP, the close relationship between them and emotional behavior, and changes in neurohormone levels in patients with eating and affective disorders seem to support these hypotheses. Moreover, their plasma levels seem to be related to the severity of psychopathological symptoms of eating disorders.


Saccharide modified pharmaceutical nanocarriers for targeted drug and gene delivery.
Nanocarriers are effective non-viral vectors for drug and gene delivery with low immunogenicity in comparison with viral vectors. However, the lack of organ or cell specificity sometimes hinders their application and brings about unexpected side effects. Active targeting is an outstanding strategy recently developed for drug delivery systems, for example, surface modification of nanocarriers with specific ligands could target the pathological area to provide the maximum therapeutic efficacy. In such cases, the characteristics of the ligands determine the active targeting abilities of the nanocarrier systems. Recently, more attentions have been paid to saccharides as ligands for saccharide-modified nanocarriers, possesing the receptor-mediated targeting properties and showing the potential for cell-specific delivery of drugs and genes. In this review, various kinds of glycosylated nanocarriers are discussed, including: varying ligands, targeting properties, therapeutic effects, and methods for administering the nanocarriers. The advantages as well as the probable associated drawbacks of these vectors are communicated.


Evaluation of subclinical atherosclerosis in migraine patients by ultrasound radiofrequency data technology: preliminary results.
Migraine is a headache disorder affecting approximately 12% of the population, predominantly female individuals. Migraine has been associated with vascular events such as stroke and cardiovascular disease. The close connection between these vascular disorders and atherosclerosis is well known. Carotid artery intima-media thickness (CAIMT) is a marker for detection of subclinical atherosclerosis. The present study is an analysis of the presence of subclinical atherosclerosis in migraine patients. CAIMT was evaluated in 25 female migraine patients and 27 female controls using innovative ultrasound (US) radiofrequency (RF) data technology. Mann-Whitney U test was used to compare measurements in patient and control groups. There was a statistically significant difference between mean CAIMT of migraine patients and control group (p<0.005): mean CAIMT was 701±114 µm in migraine patients and 400±64 µm in control group. Migraine patients are more prone to atherosclerosis compared to healthy individuals. CAIMT measurement with sonography can be utilized in follow-up to detect subclinical atherosclerosis.


A neonatal mouse model of coxsackievirus A16 for vaccine evaluation.
To evaluate vaccine efficacy in protecting against coxsackievirus A16 (CA16), which causes human hand, foot, and mouth disease (HFMD), we established the first neonatal mouse model. In this article, we report data concerning CA16-induced pathological changes, and we demonstrate that anti-CA16 antibody can protect mice against lethal challenge and that the neonatal mouse model could be used to evaluate vaccine efficacy. To establish a mouse model, a BJCA08/CA16 strain (at 260 50% lethal doses [LD(50)]) was isolated from a patient and used to intracerebrally (i.c.) inoculate neonatal mice. The infection resulted in wasting, hind-limb paralysis, and even death. Pathological examination and immunohistochemistry (IHC) staining indicated that BJCA08 had a strong tropism to muscle and caused severe necrosis in skeletal and cardiac muscles. We then found that BJCA08 pretreated with goat anti-G10/CA16 serum could significantly lose its lethal effect in neonatal mice. When the anti-G10 serum was intraperitoneally (i.p.) injected into the neonatal mice and, within 1 h, the same mice were intracerebrally inoculated with BJCA08, there was significant passive immunization protection. In a separate experiment, female mice were immunized with formaldehyde-inactivated G10/CA16 and BJCA08/CA16 and then allowed to mate 1 h after the first immunization. We found that there was significant protection against BJCA08 for neonatal mice born to the immunized dams. These data demonstrated that anti-CA16 antibody may block virus invasion and protect mice against lethal challenge, and that the neonatal mouse model was a viable tool for evaluating vaccine efficacy.


[Cerebral infarction].
Diabetes mellitus is the second major risk factor for ischemic stroke. Recent increase in atherothrombotic stroke appears to be related with recent increasing of diabetes. Diabetes is, however, a risk factor not only for atherothrombotic stroke but also for lacunar stroke because there is no difference in prevalence of diabetes between atherothrombotic and lacunar strokes. Diabetes can be a risk factor for cardioembolic stroke as well because the major cause of cardioembolic stroke is atrial fibrillation, and diabetes is a risk factor for stroke in patients with atrial fibrillation. Acute ischemic stroke should be classified into above three subtypes according to the brain and artery imaging as well as cardiac sources of embolism. In hyper-acute patients within 3 hours of onset and without early ischemic signs on CT or ischemic lesions less than one third of the hemisphere on magnetic resonance diffusion-weighted imaging, thrombolytic therapy with alteplase is indicated. In acute stroke patients later than 3 hours of onset, argatroban, heparin, and ozagrel are indicated for atherothrombotic, cardioembolic, and lacunar stroke, respectively. For stroke prevention, total management is required by simultaneous treatments for all risk factors existed. In secondary prevention for stroke, in addition to the more strict control of risk factors antithrombotic therapy is required, that is, antiplatelet therapy is indicated for non-cardioembolic stroke, and anticoagulant therapy is indicated for cardioembolic stroke.


[Japanese monograph of dietary Chinese materia medica: Ben chao shi jian].
Ben chao shi jian was a monograph of dietary Chinese materia medica written by Japanese doctor: [see text], following the style of Ben cao gang mu (Compendium of Materia Medica). The book consulted Ben cao gang mu and associated with the actual situation of Japan, making elaborate illustrations on the function, toxicity, form feature, manufacture and collection of 442 kinds of dietary Chinese material medica produced from Japan and combining organically with all kinds of knowledges including medicice and pharmacology, health preservation, nutriology and gastrology etc. It was a very important work in the developmental history of dietology and medicative dietology in Japan with high practical and academic values.


Chromatin-associated RNA sequencing (ChAR-seq) maps genome-wide RNA-to-DNA contacts.
RNA is a critical component of chromatin in eukaryotes, both as a product of transcription, and as an essential constituent of ribonucleoprotein complexes that regulate both local and global chromatin states. Here, we present a proximity ligation and sequencing method called Chromatin-Associated RNA sequencing (ChAR-seq) that maps all RNA-to-DNA contacts across the genome. Using Drosophila cells, we show that ChAR-seq provides unbiased, de novo identification of targets of chromatin-bound RNAs including nascent transcripts, chromosome-specific dosage compensation ncRNAs, and genome-wide trans-associated RNAs involved in co-transcriptional RNA processing.


The role of CD40-CD40 ligand (CD154) interactions in immunoglobulin light chain repertoire generation and somatic mutation.
To determine whether CD40 ligation influences the molecular and selective mechanisms that govern the development of the human Ig light chain repertoire, analysis of the Vkappa and Vlambda repertoires of CD19+ B cells obtained from a patient with X-linked hyper IgM syndrome (XHIM) and a nonfunctional CD154 was carried out. The nonproductive Vkappa and Vlambda repertoires were largely comparable to that of the normals with respect to V gene and J segment distribution as well as CDR3 length and VLJL joint complexity. Comparison of the nonproductive and productive repertoires indicated that a limited number of VL genes were positively and negatively selected in the XHIM patient. Although mutations were observed in the XHIM VL repertoires, the frequency of mutations was significantly lower than in normals. Typical targeting of these mutations into RGYW/WRCY motifs was significantly reduced and subsequent selection of RGYW/WRCY mutations, which is normally observed, was not found. These results indicate that CD40 ligation is not required for generation of the light chain repertoire, positive selection of some Vk rearrangements, negative selection of specific VL genes, and some degree of somatic mutation. Importantly, however, targeting of mutations to RGYW/WRCY motifs and subsequent selection of these mutated motifs does not occur in the absence of CD40 ligation.


Correlation between the American Academy of Otolaryngology-Head and Neck Surgery five-minute hearing test and standard audiologic data.
The American Academy of Otolaryngology-Head and Neck Surgery recently developed a questionnaire called the "Five-Minute Hearing Test" and distributed it to many primary care physicians. Our literature review suggests that the test characteristics (i.e., sensitivity and specificity) of this screening instrument have not been published. The purpose of this study was to examine the validity of the test by correlating the "Five-Minute Hearing Test" results to various audiologic results obtained for the same patients and to analyze the test characteristics with pure-tone measures as a standard criterion. An original version of the "Five-Minute Hearing Test" was administered to 70 patients older than 55 years, and a revised version of the test was administered to additional 74 elderly patients. The "Five-Minute Hearing Test" scores in both original and revised versions significantly correlated with all audiologic measures, especially with the pure-tone measures. However, the American Academy of Otolaryngology-Head and Neck Surgery's recommended cutoff score for a referral yielded a high false-positive rate. If the cutoff score were changed, the "Five-Minute Hearing Test" would be a reliable hearing screening tool for identification of hearing loss among the elderly population. Specific recommendations include adjustment of the cutoff score to at least 15 and revision of a few selected test items.


Integrin α1/β1 and α2/β1 as a receptor for IgA1 in human glomerular mesangial cells in IgA nephropathy.
IgA nephropathy (IgAN) is characterized by mesangial deposition of IgA1 and galactose-deficient IgA1 is expected to play a pathogenic role. However, the identity of the receptor for IgA1 is still controversial. Hence, the aim of this study was to explore the receptor for galactose-deficient IgA1. Human monoclonal IgA1 was treated with exoglycosidase and FITC-conjugated control, asialo- and agalactosyl-IgA1 was used as a probe to detect the receptor in cultured human mesangial cells. Tumor necrosis factor-α or transforming growth factor-β1 treatment accelerated IgA1-binding on mesangial cells, and these effects were diminished by the addition of dexamethasone, whereas these changes were not dependent on galactose-deficiency of IgA1. According to comprehensive gene expression analysis, we focused on integrin β1. Pre-treatment by Mn(2+), which activates integrin by changing its structure, enhanced the binding of IgA1 in cultured mesangial cells. Furthermore, pre-incubation with collagens specifically enhanced binding of IgA1 in the cultured human mesangial cells without activation by Mn(2+). Collagen type IV distributed in the mesangial region of the glomeruli as well as Bowman's capsule and tubular basal membrane in IgAN patients, and the IgA1 with collagen type IV induced proliferative signals on mesangial cells by phosphorylating extracellular signal-regulated kinase more effectively than the IgA1 alone. Immunoprecipitation assay revealed the binding of IgA1 and integrin α1/β1 and α2/β1 heterodimer and down-regulation of integrin α1, α2 and β1 expression in human mesangial cells induced by each specific small interfering RNA diminished the ability to bind IgA1 probe. Integrin α1/β1 and α2/β1 would be a candidate receptor for IgA1.


Initiation of anaemia management in patients with chronic kidney disease not on dialysis in the Veterans Health Administration.
Erythropoiesis-stimulating agents (ESAs) are frequently used to treat anaemia of chronic kidney disease (CKD) in the dialysis setting; however, few data are available regarding factors influencing initiation of ESAs and other therapies in non-dialysis patients. A retrospective cohort study of Veterans Health Administration data from 2003 to 2005 for 89 585 patients identified as having CKD and anaemia based on two outpatient estimated glomerular filtration rates <60 ml/min/1.73 m(2) and at least one outpatient haemoglobin (Hb) <11 g/dL. Hb levels, patient demographics, clinical and provider characteristics and procedures predicted ESA treatment initiation over 1 year of follow-up. Multivariable logistic and pooled logistic survival models identified predictors of ESA initiation. Overall, 6381 subjects (7.1%) initiated ESAs within 1 year of the index Hb; initiation was more common (8.6%) for patients with Hb <10 g/dL. Iron therapy use varied by initial Hb levels (27.6% to 52.4%) as did transfusions (12.5% to 42.8%); each was more common at lower Hb levels. Hbs rose to above 11 g/dL for 25-50% of patients in the absence of any treatment or by transfusion/iron therapy. Factors predicting time to ESA initiation included: nephrologist [odds ratio (OR = 2.3)] or haematologist care (OR = 2.2) and iron therapy (OR = 1.6). Transfusions increased for patients with increasing follow-up time. Iron therapy is more common than ESA treatment in patients with CKD and Hbs <11 g/dL in the VA. Correction of anaemia in the absence of any ESA treatment was common at higher Hbs levels, but much less so when Hb levels fell below 10 g/dL.


Afadin controls p120-catenin-ZO-1 interactions leading to endothelial barrier enhancement by oxidized phospholipids.
Afadin is a novel regulator of epithelial cell junctions assembly. However, its role in the formation of endothelial cell junctions and the regulation of vascular permeability remains obscure. We previously described protective effects of oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) in the in vitro and in vivo models of lung endothelial barrier dysfunction and acute lung injury, which were mediated by Rac GTPase. This study examined a role of afadin in the OxPAPC-induced enhancement of interactions between adherens junctions and tight junctions as a novel mechanism of endothelial cell (EC) barrier preservation. OxPAPC induced Rap1-dependent afadin accumulation at the cell periphery and Rap1-dependent afadin interaction with adherens junction and tight junction proteins p120-catenin and ZO-1, respectively. Afadin knockdown using siRNA or ectopic expression of afadin mutant lacking Rap1 GTPase binding domain suppressed OxPAPC-induced EC barrier enhancement and abolished barrier protective effects of OxPAPC against thrombin-induced EC permeability. Afadin knockdown also abolished protective effects of OxPAPC against ventilator-induced lung injury in vivo. These results demonstrate for the first time a critical role of afadin in the regulation of vascular barrier function in vitro and in vivo via coordination of adherens junction-tight junction interactions.


Cryotherapy in the management of trigeminal neuralgia: a review of the literature and report of three cases.
Trigeminal neuralgia is a unique neuropathic syndrome confined to the trigeminal system with no analog in the somatic dermatomes or the other cranial nerves. Medical treatment remains the first line of treatment with carbamezapine as the drug of choice. Surgery, central or peripheral is indicated when medical treatment fails or its side effects diminishes quality of life. No surgery offers a permanent cure. Recurrence rates are highest in the most peripheral techniques but these also have the lowest morbidity. Cryotherapy produces a reliable, prolonged and reversible nerve block with no aggravation of symptoms. It is a simple and repeatable procedure in patients who want to avoid major surgery or where it is contra-indicated.


The role of a template-assisted cognitive transperineal prostate biopsy technique in patients with benign transrectal prostate biopsies: a preliminary experience.
Urologists are commonly facing the dilemma of elevating prostate-specific antigen (PSA) levels despite a series of negative prostate biopsy results. Although fusion biopsies are being used increasingly, they are not available in many centers. We evaluated the prostate cancer detection rate using transperineal magnetic resonance imaging (MRI) template-guided cognitive biopsy. Twenty-two patients with a suspicious lesion on MRI were enrolled into this study and underwent a repeated biopsy. All procedures were done under anesthesia and with antibiotic prophylaxis. Brachytherapy template was applied in each case. The median age, PSA and prostate volume were 67 years, 9.2 ng/ml, and 65 ml, respectively. The average number of biopsy cores was 24. Nine patients (41%) were diagnosed with prostate cancer. The grade distribution was Gleason score 7 for 5 patients, and Gleason score 6 for 4 patients. No major complications occurred. Transperineal MRI template-guided cognitive prostate biopsy appears to be a safe procedure, which helps to detect significant cancer. The biopsy-associated adverse events are negligible.


High resolution ID-ICP-MS certification of an estuary water reference material (LGC 6016) and analysis of matrix induced polyatomic interferences.
Reliable trace metal analysis of environmental samples is dependent upon the availability of high accuracy, matrix reference standards. Here, we present Cd, Cu, Ni, Pb and Zn isotope dilution determination for an estuary water certified reference material (LGC 6016). This work highlights the need for high-accuracy techniques in the development of trace element CRMs rather than conventional inter-laboratory trials. Certification of the estuary water LGC6016 was initially determined from a consensus mean from 14 laboratories but this was found to be unsatisfactory due to the large discrepancies in the reported concentrations. The material was re-analysed using isotope dilution ICP-MS techniques. Pb and Cd were determined using a conventional quadrupole ICP-MS (Elan 5000). Cu, Zn and Ni were determined using a magnetic sector ICP-MS (Finnigan Element), which allowed significant polyatomic interferences to be overcome. Using the magnetic sector instrument, precise mass calibration to within 0.02 amu permitted identification of the interferences. Most interferences derived from the sample matrix. For example, the high Na content causes interferences on 63Cu, due to the formation of 40Ar23Na and 23Na2 16O1H, which in a conventional quadrupole instrument would relate to an erroneous increase in signal intensity by up to 20%. For each analyte a combined uncertainty calculation was performed following the Eurachem/GTAC and ISO guideline. For each element a combined uncertainty of 2-3% was found, which represents a 10-fold improvement compared to certification by inter-laboratory comparison. Analysis of the combined uncertainty budget indicates that the majority of systematic uncertainty derives from the instrumental isotope ratio measurements.


Sporadic inclusion body myositis: pilot study on the effects of a home exercise program on muscle function, histopathology and inflammatory reaction.
To evaluate the safety and effect of a home training program on muscle function in 7 patients with sporadic inclusion body myositis. The patients performed exercise 5 days a week over a 12-week period. Safety was assessed by clinical examination, repeated muscle biopsies and serum levels of creatine kinase. Muscle strength was evaluated by clinical examination, dynamic dynamometer and by a functional index in myositis. Strength was not significantly improved after the exercise, however none of the patients deteriorated concerning muscle function. The histopathology was unchanged and there were no signs of increased muscle inflammation or of expression of cytokines and adhesion molecules in the muscle biopsies. Creatine kinase levels were unchanged. A significant decrease was found in the areas that were positively stained for EN-4 (a marker for endothelial cells) in the muscle biopsies after training. The home exercise program was considered as not harmful to the muscles regarding muscle inflammation and function. Exercise may prevent loss of muscle strength due to disease and/or inactivity.


Supervision and mentorship: the use of the real in teaching.
The supervisory relationship between psychoanalysts and dynamic psychotherapists and their supervisees has from the beginning of our history been difficult to define, because it frequently transgresses the boundaries of personal analysis and didactic teaching and learning. This article attempts to summarize the history of our approaches to supervision with particular reference to interpersonal paradigms. Clinical vignettes of supervisory difficulties for both supervisor and supervisee illustrate these approaches. Some reference is also made to cross-cultural supervision and the future of this discipline.


[Effects of rhTNF-alpha on the secretion of angiogenesis-related growth factors of human adipose tissue-derived stromal cells before and after osteogenic differentiation].
To investigate the proliferation and the secretion of vascular endothelial growth factor(VEGF), fibroblast growth factor-2(FGF-2) and insulin-like growth factor-1(IGF-1) of human adipose tissue-derived stromal cells(hADSCs) before and after osteogenic differentiation under the stimuli of recombinant human tumor necrosis factor alpha (rhTNF-alpha). hADSCs were obtained from human lipoaspirates. All the cells used were at passage four. The proliferation of hADSCs was measured with MTT assays 48, 72, 96 hours after being treated with 0, 1, 5, 10, 50 or 100 microg/L rhTNF-alpha respectively. The secretion of VEGF, FGF-2 and IGF-1 of the undifferentiated hADSCs under stimuli of rhTNF-alpha with the above 5 concentration grades was observed and the secretion of these 3 growth factors of hADSCs at different stages of osteogenic differentiation under stimuli of 10 microg/L rhTNF-alpha was also observed. All the supernatants were harvested for measuring after 24 hours' incubation with rhTNF-alpha. The secretion of VEGF, FGF-2 and IGF-1 was measured with ELISA, and the values were normalized to the cell number of the corresponding wells. The effect of rhTNF-alpha on the proliferation of hADSCs varied with the concentration and time. Compared with the control(0 microg/L), 10 microg/L rhTNF-alpha showed no suppression or acceleration on proliferation of hADSCs at hour 48, but significantly promoted the proliferation at hour 96 (0.903+/-0.042 vs 0.810+/-0.011, P<0.01), 100 microg/L rhTNF-alpha seemed to suppress the proliferation at hour 48 (0.317+/-0.024 vs 0.458+/-0.046, P<0.01), but appeared to promote it (0.956+/-0.030 vs 0.810+/-0.011, P<0.01) at hour 96. rhTNF-alpha(1, 5, 10, 50 and 100 microg/L) significantly increased VEGF, FGF-2 and IGF-1 production of hADSCs versus the control (0 microg/L) (P<0.01). After osteogenic differention, the secretion of the three growth factors of hADSCs (without rhTNF-alpha treated) was elevated with the days increasing. Under the stimulus of 10 microg/L rhTNF-alpha, the hADSCs after 1 day of osteogenic differentiation significantly increased the secretion of VEGF (P<0.01) compared with the group without rhTNF-alpha treated; after 3 and 7 days of osteogenic differentiation, the hADSCs significantly increased the secretion of VEGF (P<0.01), FGF-2 (P<0.05)and IGF-1 (P<0.05). However, after 14 days of osteogenic differentiation, 10 microg/L rhTNF-alpha appeared to suppress the production of VEGF (P<0.01), FGF-2 (P<0.05) and IGF-1 (P<0.05) of the differentiated hADSCs. Within certain concentration range, rhTNF-alpha can promote the proliferation of hADSCs and the production of VEGF, FGF-2 and IGF-1. The effect of 10 microg/L rhTNF-alpha on the production of VEGF, FGF-2 and IGF-1 of the differentiated hADSCs varied at different stages of osteogenic differentiation.


Deciphering the Complex Molecular Pathogenesis of Myotonic Dystrophy Type 1 through Omics Studies.
Omics studies are crucial to improve our understanding of myotonic dystrophy type 1 (DM1), the most common muscular dystrophy in adults. Employing tissue samples and cell lines derived from patients and animal models, omics approaches have revealed the myriad alterations in gene and microRNA expression, alternative splicing, 3' polyadenylation, CpG methylation, and proteins levels, among others, that contribute to this complex multisystem disease. In addition, omics characterization of drug candidate treatment experiments provides crucial insight into the degree of therapeutic rescue and off-target effects that can be achieved. Finally, several innovative technologies such as single-cell sequencing and artificial intelligence will have a significant impact on future DM1 research.


Conventional and molecular methods for verification of results obtained with BacT/Alert Nonvent blood culture bottles.
A strategy comparing molecular and conventional methods for verification of the BacT/Alert nonvent blood culture bottles (Organon Teknika, Durham, N.C.) was performed with seeded isolates. The bottles were evaluated with 12 common organisms from bloodstream infections. Overall, the bottles were equivalent as determined by conventional and molecular methods.


DNA barcoding as a valuable tool for delimiting mollusk species of the genus Biomphalaria Preston, 1910 (Gastropoda: Planorbidae).
The genus Biomphalaria in Brazil includes 11 species and one subspecies, three of which are intermediate hosts of Schistosoma mansoni. Due to the recent evolution of this group, some species are difficult to identify based on morphological characters, making the use of genetic markers necessary for species identification. This study aimed to evaluate the use of partial sequences of the cytochrome c oxidase I (coi) gene for the identification of Biomphalaria species using phylogenetic reconstruction and species delimitation algorithms. The study tested the use of DNA barcoding technique for species delimitation within the genus. DNA barcoding was performed by sequencing a partial region of the coi gene from specimens, and the sequences were analyzed using phylogenetic reconstruction and algorithms to delimit Operational Taxonomic Units (OTUs). The study found that the use of the coi gene in the reconstruction of the phylogeny of the genus might be an alternative for understanding the evolution and dispersion of species. However, this marker alone is not enough to solve complex taxonomic problems within the genus. A total of 223 sequences were analyzed, 102 of which could be separated using the barcode gap, enabling the correct identification of seven taxa. The study demonstrated that accurate mollusk identification is necessary for effective schistosomiasis control. The DNA barcoding methodology was found to be promising for accurate mollusk identification, which is crucial for concentrating schistosomiasis control efforts in places where it is needed.


Reversibility of structural transition of cytochrome c on interacting with and releasing from alternating copolymers of maleic Acid and alkene.
The interaction of cytochrome c (cyt c) with poly(isobutylene-alt-maleic acid) (PIMA) and poly(1-tetradecene-alt-maleic acid) (PTMA) was studied using circular dichroism, absorption spectroscopy, and atomic force microscopy to investigate the electrostatic and hydrophobic influence of the copolymers on the structure of cyt c. At pH 7.4, the interaction of PIMA with cyt c can only partly disturb the integrity of the heme pocket, while PTMA has very intensive influence on the structure of cyt c. After adding 0.15 M NaCl, PIMA-cyt c complexes dissociate, and the released cyt c recovers its native structure, whereas NaCl has no significant influence on PTMA-cyt c complexes. GuHCl (0.5 M) destroys PTMA-cyt c complexes, forming GuHCl-PTMA precipitates; the cyt c released from the complexes regenerates its native structure. In comparison with electrostatic interaction, hydrophobic interaction leads to more stable polymer-cyt c complexes and more intensive influence on cyt c structure, but cyt c can recover its native state after release.


Comparison of Different Chemical and Mechanical Modalities for Implant Surface Decontamination: Activity against Biofilm and Influence on Cellular Regrowth-An In Vitro Study.
The aim of this in vitro study was to compare the efficacy of chemical and mechanical methods for decontamination of titanium dental implant surfaces previously infected with polymicrobial biofilms in a model simulating a peri-implant defect. Furthermore, the effect of each decontamination protocol on MG-63 osteoblast-like cells morphology and adhesion to the treated implants was assessed. Peri-implantitis is a growing issue in dentistry, and evidence about implant surface decontamination procedures is lacking and inconclusive. A total of 40 previously biofilm-contaminated implants were placed into a custom-made model simulating a peri-implant defect and randomly assigned to five treatment groups: (C) control (no treatment); (AW) air abrasion without any powder; (ESC) air abrasion with powder of erythritol, amorphous silica, and 0.3% chlorhexidine; (HBX) decontamination with a sulfonic/sulfuric acid solution in gel; and (HBX + ESC) a combination of HBX and ESC. Microbiological analysis was performed on five implants per treatment group, and the residual viable bacterial load measured in log 10 CFU/mL was counted for each bacterial strain and for the total number of colonies. The remaining three implants per group and three noncontaminated (NC) implants were used to assess surface biocompatibility using a scanning electron microscope and a backscattered electron microscope after seeding with MG-63 cells. A significant decontaminant effect was achieved using HBX or HBX + ESC, while no differences were observed among other groups. The percentage of implant surface covered by adherent MG-63 cells was influenced by the treatment method. Progressive increases in covered surfaces were observed in groups C, AW, ESC, HBX, HBX + ESC, and NC. A combination of mechanical and chemical decontamination may provide more predictable results than mechanical cleaning alone.


Predictors of Crohn's disease.
Early intensive therapy in Crohn's disease should be considered only in patients with disabling disease. The aim of our study was to identify at diagnosis factors predictive of a subsequent 5-year disabling course. Among the 1526 patients seen at our unit with Crohn's disease diagnosed between 1985 and 1998, we excluded patients operated on within the first month of the disease, patients with inadequate data, and patients with severe chronic nondigestive disease. In the 1188 remaining patients, Crohn's disease course within the first 5 years of the disease was categorized as disabling when at least 1 of the criteria of clinical severity, conventionally predefined, was present. Among the 1123 patients with follow-up data allowing full 5-year course classification, the rate of disabling disease was 85.2%. Independent factors present at diagnosis and significantly associated with subsequent 5-year disabling were the initial requirement for steroid use (OR 3.1 [95% CI: 2.2-4.4]), an age below 40 years (OR 2.1 [95% CI: 1.3-3.6]), and the presence of perianal disease (OR 1.8 [95% CI: 1.2-2.8]). The positive predictive value of disabling disease in patients with 2 and 3 predictive factors of disabling disease was 0.91 and 0.93, respectively. These values were 0.84 and 0.91, respectively, when tested prospectively in an independent group of 302 consecutive patients seen at our institution from 1998. At diagnosis of Crohn's disease in a referral center, factors predictive of subsequent 5-year disabling course are an age below 40 years, the presence of perianal disease, and the initial requirement for steroids.


Pulmonary presentation of Toxocara sp. infection in children.
The aim of this study was to investigate the associations between radiological findings, blood eosinophilia, hyperimmunoglobulinemia E and G and Toxocara seropositivity in Polish children with newly diagnosed pulmonary infiltration. We retrospectively analyzed the documentation of 119 patients, aged 1 to 18 years (mean age: 7.21 ± 4.82), who were seropositive in Toxocara sp. antibodies. In all cases, peripheral blood eosinophils and leukocyte counts, serum total IgE, IgG levels and specific IgG antibodies against excretory and secretory Toxocara sp. antigens were measured at the first presentation. After the confirmation of seropositivity, all children had a routine radiological examination. In the documentation of 23 children (mean age 3.58 ± 2.63 years) we found abnormalities in the radiological examination of their lungs. Fifteen children who had abnormalities in radiological findings presented clinical respiratory complaints such as chronic cough, wheezing, asthma and haemoptysis. Eight children were asymptomatic. The analysis of peripheral eosinophils and leukocyte number, the level of IgE and specific anti-Toxocara IgG presented significantly higher values in children with radiological lesions than in children who had correct radiology. The concentrations of total IgG and gamma globulins were not significantly different. In 10 patients CT showed irregular round nodules with and without halo ranging from 1 to 13 mm. The number of nodules varied from a single lesion to multiple, disseminated ones. All nodules were located in peripheral areas of the lungs. None of them were found in the central areas. In 13 patients, CT images showed ground-glass opacities with ill-defined margins. None of the CT images presented lymphadenopathy and pleural effusion. The pulmonary lesions in small children with high eosinophilia and hyperimmunoglobulinemia E could be related to toxocariasis and for this reason they are eligible to undergo therapy with prolonged observation for several months, rather than start invasive malignancy investigations.


Preoperative serum thyroglobulin as a useful predictive marker to differentiate follicular thyroid cancer from benign nodules in indeterminate nodules.
Indeterminate cytology results increase the number of repetitive procedure and unnecessary surgery. This study was designed to find useful and simple predictive tools to differentiate malignant thyroid nodules from indeterminate nodules. We retrospectively enrolled 164 patients who had undergone thyroid surgery as a result of indeterminate cytology in the National Cancer Center. We reviewed patients' age at diagnosis, sex, preoperative biochemical markers such as thyroglobulin (Tg), anti-Tg antibody, free T4 and TSH level, and sonographical and pathological findings, which were subjected to statistical analysis. We found several clinical and sonographical predictive factors that showed significant differences. Young age, male, preoperative high Tg level, and hypoechoic nodule on sonography all increased cancer probability significantly in multivariate analysis. With a cut-off value of 187.5 ng/mL Tg, sensitivity and specificity were 54.8% and 90.1%, respectively (AUC 0.748, P < 0.001). In the case of nodule size > 1.7 cm, elevated serum Tg predicts the risk of malignancy; especially Tg > 70 ng/mL (odds ratio 3.245, 95% confidence interval 1.115-9.450, P = 0.038). Preoperative Tg levels had very high specificity in predicting thyroid cancer in case of suspicious follicular neoplasm. Therefore, Tg levels may be a useful marker for differentiating thyroid cancer from benign thyroid nodules in the cytological diagnosis of indeterminate nodules.


Accelerated decline in cardiac stem cell efficiency in Spontaneously hypertensive rat compared to normotensive Wistar rat.
Cardiac hypertrophy is recognized as an independent risk factor for cardiac failure. Efficient management of hypertensive heart disease requires identification of factors that can possibly mediate the transition from hypertrophy to failure. Resident cardiac stem cells have a prominent role in the maintenance of cardiac tissue homeostasis. Decline in the proportion of healthy cardiac stem cells (CSCs) can affect tissue regeneration. In pathological conditions, apart from natural aging, an adverse microenvironment can lead to decrease in efficiency of CSCs. A systematic analysis of cardiac stem cell characteristics in pathological conditions has not been reported so far. Therefore, this study was designed with the objective of examining the age associated variation in stem cell attributes of Spontaneously hypertensive rat (SHR) in comparison with normotensive Wistar rat. Spontaneously hypertensive rat was used as the experimental model since the cardiac remodeling resembles the clinical course of hypertensive heart disease. CSCs were isolated from atrial explants. Stem cell attributes were assessed in 1-week, 6, 12 and 18-month-old male SHR, in comparison with age matched Wistar rats. In 1-week-old pups, stem cell attributes of SHR and Wistar were comparable. Migration potential, proliferative capacity, TERT expression, telomerase activity and the proportion of c-kit+ cells decreased with age, both in SHR and Wistar. DNA damage and the proportion of senescent CSCs increased with age both in SHR and Wistar rats. Age associated increase was observed in the oxidative stress of stem cells, possibly mediated by the enhanced oxidative stress in the microenvironment. The changes were more pronounced in SHR, and as early as six months of age, there was significant decrease in efficiency of CSCs of SHR compared to Wistar. The density of healthy CSCs determined as a fraction of the differentiated cells was remarkably low in 18-month-old SHR. Age associated decrease in functionally efficient CSCs was therefore accelerated in SHR. Considering the vital role of CSCs in the maintenance of a healthy myocardium, decrease in functionally efficient CSCs can be a precipitating factor in pathological cardiac remodeling. Elevated ROS levels in CSCs of SHR lends scope for speculation that decrease in efficiency of CSCs is mediated by oxidative stress; and that modulation of the microenvironment by therapeutic interventions can restore a healthy stem cell population and facilitate maintenance of cardiac homeostasis and prevent cardiac decompensation.


Effects of Prior Tracheostomy on Total Laryngectomy Outcomes.
To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. Retrospective cohort study. Tertiary care hospital between 2007 and 2020. Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.


Facile synthesis of polypyrrole coated copper nanowires: a new concept to engineered core-shell structures.
Polypyrrole coated copper nanowires were synthesized in a one-pot manner in the presence of cupric precursor and pyrrole. They displayed ultra-high sensitivity as a potentiometric sensor with considerable environmental stability comparable to noble metals.


DNA topoisomerases in cancer chemotherapy: using enzymes to generate selective DNA damage.
DNA topoisomerase II targeting agents such as etoposide and doxorubicin are well-established cancer chemotherapeutic agents. Topotecan (Hycamtin) and irinotecan (Camptosar) are launched drugs that target topoisomerase I and have significant activity against many solid malignancies. These agents have important mechanistic similarities, converting their target enzyme(s) to generate DNA damage. Recent structural and biochemical studies on targeting of topoisomerases by antitumor agents are providing a framework for understanding drug action at the enzyme level, and at the level of cellular pathways important for responses to this unique type of DNA damage. These investigations into the mechanisms of action of topoisomerase-targeting agents should aid in the design of dinical protocols that optimize the activity of these agents.