Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells.
Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCT-positive subpopulation and show relatively low expression of osteogenic markers during in vitro osteogenic differentiation. Sulfasalazine (SSZ), a drug used to treat rheumatoid arthritis, suppresses xCT expression in cancer cells. In this study, we found that the SSZ treatment at 100 µM significantly suppressed xCT mRNA expression in CADSCs but did not significantly affect cell proliferation under the same conditions. Additionally, this treatment decreased the intracellular glutathione concentration. During in vitro osteogenic differentiation, the SSZ treatment at 50 µM and 100 µM significantly increased alizarin red staining and its quantification, as well as the concentration-dependent osteogenic differentiation markers (BMP1 and SPP) mRNA expression. Our results suggested that SSZ enhances the osteogenic differentiation potential of CADSCs and can potentially exhibit a superior therapeutic profile in canine bone regenerative medicine.


Coke- and sintering-resistant monolithic catalysts derived from in situ supported hydrotalcite-like films on Al wires for dry reforming of methane.
Monolithic catalysts derived from in situ supported hydrotalcite-like films on Al wires display high resistance to coke formation and sintering in the dry reforming of methane due to their hierarchical porous structure, well dispersed metallic nickel species, more basic sites and strong metal-support interaction effect.


Chronic tumor necrosis factor alters T cell responses by attenuating T cell receptor signaling.
Repeated injections of adult mice with recombinant murine TNF prolong the survival of NZB/W F1 mice, and suppress type I insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice. To determine whether repeated TNF injections suppress T cell function in adult mice, we studied the responses of influenza hemagglutinin-specific T cells derived from T cell receptor (HNT-TCR) transgenic mice. Treatment of adult mice with murine TNF for 3 wk suppressed a broad range of T cell responses, including proliferation and cytokine production. Furthermore, T cell responses of HNT-TCR transgenic mice also expressing the human TNF-globin transgene were markedly reduced compared to HNT-TCR single transgenic littermates, indicating that sustained p55 TNF-R signaling is sufficient to suppress T cell function in vivo. Using a model of chronic TNF exposure in vitro, we demonstrate that (a) chronic TNF effects are dose and time dependent, (b) TNF suppresses the responses of both Th1 and Th2 T helper subsets, (c) the suppressive effects of endogenous TNF produced in T cell cultures could be reversed with neutralizing monoclonal antibodies to TNF, and (d) prolonged TNF exposure attenuates T cell receptor signaling. The finding that anti-TNF treatment in vivo enhances T cell proliferative responses and cytokine production provides evidence for a novel regulatory effect of TNF on T cells in healthy laboratory mice. These effects are more pronounced in chronic inflammatory disease. In addition, our data provide a mechanism through which prolonged TNF exposure suppresses disease in animal models of autoimmunity.


Can adults living with dementia complete pure-tone audiometry? A systematic review.
It is estimated that over 60% of adults with dementia will also have a hearing impairment, resulting in a dual sensory-cognitive communication disability. Hearing interventions may lessen the impact of hearing impairment on a communication disability; yet, for audiologists to recommend appropriate hearing interventions, the individual's hearing thresholds must first be accurately established. The gold standard test for establishing hearing thresholds is pure-tone audiometry (PTA). However, the ability of adults with dementia to successfully complete PTA is uncertain. This systematic review examined studies of adults with dementia to better determine the proportion who could complete PTA. Systematic review. Studies were included that assessed hearing in older adults who were reported as having mild and greater dementia. From a total of 1,237 eligible studies, only three were found to meet all inclusion criteria. Across these three studies, the proportion of adults with dementia who could successfully complete PTA ranged from 56% to 59%. Further research is needed in this area, particularly for adults with moderate and severe stages of dementia. Future research should also consider the feasibility of complementary, non-behavioural hearing tests. This systematic review was registered with the PROSPERO database, registration number CRD42017073041.


The effect of leptin on intestinal recovery following ischemia-reperfusion injury in a rat.
Recent evidence suggests that the adipose tissue derived cytokine leptin (LEP) is involved in the modulation of growth and differentiation of normal small intestine. The purpose of the present study was to examine the effect of leptin on enterocyte turnover and intestinal recovery after ischemia-reperfusion (IR) injury in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy, (2) IR-rats underwent occlusion of both superior mesenteric artery and portal vein for 30 min followed by 24 h of reperfusion, and (3) IR-LEP rats underwent IR and were treated with leptin given subcutaneously at a dose of 50 microg/kg once a day for 48 h before and 24 h following IR. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis were determined 24 h following IR. A non-parametric Kruskal-Wallis ANOVA test was used for statistical analysis with P < 0.05 considered statistically significant. Treatment with leptin resulted in a significant increase in bowel weight in ileum, mucosal weight in jejunum and ileum, mucosal DNA content in ileum, mucosal protein content in jejunum and ileum, villus height in jejunum and ileum, and crypt depth in jejunum compared to IR-animals. IR-LEP rats also had a significantly lower intestinal injury score as well as lower apoptotic index and higher cell proliferation index in jejunum and ileum compared to the IR-animals. In conclusion, pre-treatment with leptin prevents gut mucosal damage and improves intestinal rehabilitation following intestinal IR in a rat.


Rehabilitation following lumbosacral percutaneous nucleoplasty: a case report.
Case report. Lumbar spine nucleoplasty is a new surgical option for patients with disc pathology. There are no reports in the literature describing the role of physical therapy in postoperative lumbar nucleoplasty management. The purpose of this case is to describe the postoperative physical therapy management of a patient who underwent this procedure. A 50-year-old male, 7 weeks following a L5/S1 lumbar nucleus replacement, completed 6 weeks of rehabilitation. The focus of the treatment was controlled reloading of the spine through a spinal stabilization progression in weight-bearing and non-weight-bearing activities. In addition, education, spinal manual therapy techniques, and a home exercise program were also incorporated. The patient's Oswestry Disability Index decreased from 56% to 4% over 6 weeks of treatment. When contacted at 6, 12, 18, and 24 months posttherapy, his Oswestry Disability Index was 2%, 2%, 0%, and 0%, respectively, and he had returned to all previous activities without recurrence of symptoms. This case report outlines the clinical decision-making process during the postoperative management of an individual who had undergone a single-level lumbar nucleoplasty. A postoperative regimen of education, segmental spinal stabilization, and a home exercise program might have contributed to the observed improvement in pain and disability levels in this patient. The role of these postoperative interventions warrants further research. Therapy, level 4.


Study of interdigitated electrode arrays using experiments and finite element models for the evaluation of sterilization processes.
In this work, a sensor to evaluate sterilization processes with hydrogen peroxide vapor has been characterized. Experimental, analytical and numerical methods were applied to evaluate and study the sensor behavior. The sensor set-up is based on planar interdigitated electrodes. The interdigitated electrode structure consists of 614 electrode fingers spanning over a total sensing area of 20 mm². Sensor measurements were conducted with and without microbiological spores as well as after an industrial sterilization protocol. The measurements were verified using an analytical expression based on a first-order elliptical integral. A model based on the finite element method with periodic boundary conditions in two dimensions was developed and utilized to validate the experimental findings.


ADAM12-mediated focal adhesion formation is differently regulated by beta1 and beta3 integrins.
ADAM12, adisintegrin and metalloprotease, has been demonstrated to be upregulated in human malignant tumors and to accelerate the malignant phenotype in a mouse model for breast cancer. ADAM12 is a substrate for beta1 integrins and may affect tumor and stromal cell behavior through its binding to beta1 integrins. Here, we report that cells deficient in beta1 integrin or overexpressing beta3 integrin can bind to recombinant full-length human ADAM12 via beta3 integrin. Furthermore, cell binding to ADAM12 via beta3 integrin results in the formation of focal adhesions, which are not formed upon beta1 integrin-mediated cell attachment. We also show that RhoA is involved in beta3 integrin-mediated focal adhesion formation.


Embryonic implantation in galectin 1/galectin 3 double mutant mice.
Galectin 1 and galectin 3 are first expressed in the trophectoderm cells of the implanting embryo and have been implicated in the process of implantation. However, we had previously shown that the lack of galectin 1 in galectin 1 null mutant mice is compatible with implantation. In this study, we describe the generation of galectin 3 null mutant mice and show that they are viable and have no overt abnormalities. The importance of galectin 1 and galectin 3 in implantation was assessed by obtaining double mutant mice [gal1 -/-; gal3 -/-]. We find that implantation can still occur in the absence of both galectin 1 and galectin 3. However, we show that galectin 5, a third member of this gene family, is also present in the blastocyst at the time of implantation.


Visual geometry Group-UNet: Deep learning ultrasonic image reconstruction for curved parts.
Detecting small defects in curved parts through classical monostatic pulse-echo ultrasonic imaging is known to be a challenge. Hence, a robot-assisted ultrasonic testing system with the track-scan imaging method is studied to improve the detecting coverage and contrast of ultrasonic images. To further improve the image resolution, we propose a visual geometry group-UNet (VGG-UNet) deep learning network to optimize the ultrasonic images reconstructed by the track-scan imaging method. The VGG-UNet uses VGG to extract advanced information from ultrasonic images and takes advantage of UNet for small dataset segmentation. A comparison of the reconstructed images on the simulation dataset with ground truth reveals that the peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) can reach 39 dB and 0.99, respectively. Meanwhile, the trained network is also robust against the noise and environmental factors according to experimental results. The experiments indicate that the PSNR and SSIM can reach 32 dB and 0.99, respectively. The resolution of ultrasonic images reconstructed by track-scan imaging method is increased approximately 10 times. All the results verify that the proposed method can improve the resolution of reconstructed ultrasonic images with high computation efficiency.


[Preventive efficiency of IVIgG on nosocomial infection in the children with nephrotic syndrome].
In order to study the preventive efficiency of IVIgG on nosocomial infection(NI), 54 cases of the children with nephrotic syndrome(NS) were randomly divided into 2 groups, test group(n = 22) and control group(n = 32). Routine treatment was adopted to all cases. Besides the routine treatment, the test group was injected with IVIgG(100-300 mg.kg-1.d-1) for 2-3 days. The results showed that the NI rate of test group (13.6%) was significantly lower than that of the control(46.88%) (P < 0.05), and the hospital days of the test group(27.33 +/- 15.51) d was significantly shorter than that of the control(64.50 +/- 18.52) d (P < 0.05). These suggest that IVIgG, as one of the ways to prevent NI, can improve the immune state and effectively prevent the NI in the children with NS.


Elevated vasopressin in pregnant mice induces T-helper subset alterations consistent with human preeclampsia.
The pathogenesis of preeclampsia (PreE), a hypertensive disorder of pregnancy, involves imbalanced T helper (TH) cell populations and resultant changes in pro- and anti-inflammatory cytokine release. Elevated copeptin (an inert biomarker of arginine vasopressin (AVP)), secretion precedes the development of symptoms in PreE in humans, and infusion of AVP proximal to and throughout gestation is sufficient to initiate cardiovascular and renal phenotypes of PreE in wild-type C57BL/6J mice. We hypothesize that AVP infusion in wild-type mice is sufficient to induce the immune changes observed in human PreE. AVP infusion throughout gestation in mice resulted in increased pro-inflammatory interferon γ (IFNg) (TH1) in the maternal plasma. The TH17-associated cytokine interleukin (IL)-17 was elevated in the maternal plasma, amniotic fluid, and placenta following AVP infusion. Conversely, the TH2-associated anti-inflammatory cytokine IL-4 was decreased in the maternal and fetal kidneys from AVP-infused dams, while IL-10 was decreased in the maternal kidney and all fetal tissues. Collectively, these results demonstrate the sufficiency of AVP to induce the immune changes typical of PreE. We investigated if T cells can respond directly to AVP by evaluating the expression of AVP receptors (AVPRs) on mouse and human CD4+ T cells. Mouse and human T cells expressed AVPR1a, AVPR1b, and AVPR2. The expression of AVPR1a was decreased in CD4+ T cells obtained from PreE-affected women. In total, our data are consistent with a potential initiating role for AVP in the immune dysfunction typical of PreE and identifies putative signaling mechanism(s) for future investigation.


A sheep model for the study of focal epilepsy with concurrent intracranial EEG and functional MRI.
We describe a sheep model of penicillin-induced seizure activity using electroencephalography (EEG) and functional MRI (fMRI). Ten adult sheep were used. Spikes and seizures were generated by instillation of 8,000-10,000 IU of penicillin into the right prefrontal cortex via a specially designed port. Bilateral intracranial EEG was acquired by using carbon fiber electrodes. Animals had behavioral characterization of their seizures and were then anesthetized for fMRI studies. Functional MRI was performed at 1.5 and 3 Tesla by measuring blood oxygen level-dependent (BOLD) weighted signal intensity at different times during the evolution of seizures. Behavioral seizures were associated with electrographic seizures. Intracranial EEG obtained in the MR scanner was of high quality. Focal spiking and seizures were seen in all animals and developed 11.3 +/- 11.2 s and 17.3 +/- 12.1 min after penicillin administration, respectively. An average of 13 +/- 4.8 seizures were seen per animal, each lasting 27.3 +/- 12.3 s. Functional MR images with little parenchymal artefact were obtained. Regional BOLD signal-intensity changes were observed during seizures at the seizure focus and ipsilateral amygdala. We have developed an animal model of partial epilepsy in which seizures can be reliably elicited with concurrent fMRI and intracranial EEG. During unilateral electrographic seizures, focal BOLD signal changes occurred at the seizure focus and ipsilateral amygdala, suggesting the presence of a cortico-subcortical loop. This observation illustrates the potential of the model for understanding seizure generation, spread, and possibly the consequences of repeated seizures on the brain.


GATA-2 and HNF-3beta regulate the human alcohol dehydrogenase 1A (ADH1A) gene.
In this paper, we have identified several distal cis-acting elements that contribute to the regulation and tissue- specificity of ADH1A, which encodes an alcohol dehydrogenase (ADH) that metabolizes ethanol. A negative element from bp -1873 to -1558, relative to the translational start site, decreased transcriptional activity to 52% in H4IIE-C3 cells and 70% in CV-1 cells. A positive element from bp -2459 to -2173 increased transcriptional activity twofold in H4IIE-C3 cells and 1.7-fold in CV-1 cells. Gel mobility shift and supershift assays demonstrated that GATA-2 bound a region within this positive element. A tissue-specific regulatory element from bp -6380 to -5403 increased transcription twofold in H4IIE-C3 cells while decreasing transcription to 86% in CV-1 cells. Within this tissue-specific fragment, the region from bp -5668 to -5403 increased transcription 1.7-fold in H4IIE-C3 cells and 1.3-fold in CV-1 cells. Hepatocyte nuclear factor-3beta (HNF- 3beta) bound a region of the tissue-specific element in CV-1 cells, but not in H4IIE-C3 cells. Positive regulation of the ADH1A gene may be influenced by GATA-2 binding, while differences in HNF-3beta binding in cells/tissues may contribute to tissue specificity.


Can oral rinses play a role in preventing transmission of Covid 19 infection?
This narrative review describes the existing body of evidence supporting the potential role of oral rinses in preventing the transmission of SARS-CoV2. Multiple sources were searched for evidence including PubMed, Researchgate and Google Scholar. References that were identified were then investigated further to find additional source material and the original primary research. Academic and clinical experts were consulted for additional input on virology, immunology, lipid biochemistry, microbicides as well as dental and clinical practice. The authors also collaborated with a number of commercial companies to acquire information on the specific formulations of oral rinses, information not available within the public domain. There were no restrictions on language for the search strategy.


Risk for oral cancer from smokeless tobacco.
Tobacco products which are used in a way other than smoking are known as smokeless tobacco. The most common smokeless tobaccos are chewing tobacco, naswar, snuff, snus, gutka, and topical tobacco paste. Any product which contains tobacco is not safe for human health. There are more than twenty-five compounds in smokeless tobacco which have cancer causing activity. Use of smokeless tobacco has been linked with risk of oral cancer. Smokeless tobacco contains tobacco-specific nitrosamines (TSNAs), polonium, formaldehyde, cadmium, lead, and benzo[a]pyrene, which are carcinogenic agents. Although there is presence of some compounds, carotenoids and phenolic compounds, that have cancer inhibiting properties, they are in low concentrations. Dry snuff use is linked with higher relative risks, while the use of other smokeless tobacco is of intermediate risk. Moist snuff and chewing tobacco have a very low risk for oral cancer. Therefore, from this review article, it was concluded that smokeless tobacco has risk for oral cancer - either low, medium or high depending on the balance between cancer causing agents and cancer inhibiting agents.


Interobserver variations of target volume delineation and its impact on irradiated volume in accelerated partial breast irradiation with intraoperative interstitial breast implant.
To investigate the interobserver variations in delineation of lumpectomy cavity (LC) and clinical target volume (CTV), and its impact on irradiated volume in accelerated partial breast irradiation using intraoperative multicatheter brachytherapy. Delineation of LC and CTV was done by five radiation oncologists on planning computed tomography (CT) scans of 20 patients with intraoperative interstitial breast implant. Cavity visualization index (CVI), four-point index ranging from (0 = poor) to (3 = excellent) was created and assigned by observers for each patient. In total, 200 contours for all observers and 100 treatment plans were evaluated. Spatial concordance (conformity index, CIcommon, and CIgen), average shift in the center of mass (COM), and ratio of maximum and minimum volumes (Vmax/Vmin) of LC and CTV were quantified among all observers and statistically analyzed. Variation in active dwell positions (0.5 cm step) for each catheter, total reference air kerma (TRAK), volume enclosed by prescription isodose (V100%) among observers and its spatial concordance were analyzed. The mean ± SD CIcommon of LC and CTV was 0.54 ± 0.09, and 0.58 ± 0.08, respectively. Conformity index tends to increase, shift in COM and Vmax/Vmin decrease significantly (p < 0.05), as CVI increased. Out of total 309 catheters, 29.8% catheters had no change, 29.8% and 17.5% catheters had variations of 1 and 2 dwell positions (0.5 cm and 1 cm), respectively. 9.3% catheters shown variations ≥ 10 dwell positions (5 cm). The mean ± SD CIcommon of V100% was 0.75 ± 0.11. The mean observed Vmax/Vmin of prescription isodose and TRAK was 1.18 (range, 1.03 to 1.56) and 1.11 (range, 1.03 to 1.35), respectively. Interobserver variability in delineation of target volume was found to be significantly related to CVI. Smaller variability was observed with excellent visualization of LC. Interobserver variations showed dosimetric impact on irradiation of breast tissue volume with prescription dose.


Esophageal perforation as a complication of EndoCinch endoluminal gastroplication.
Endoscopic gastroplasty is being promoted as a new minimally invasive procedure for the treatment of gastroesophageal reflux disease. In the case presented here, however, we encountered abdominal perforation as a severe complication of this procedure. Because immediate action was taken when the symptoms developed, and by maintaining close collaboration with the surgeons, it was possible to keep the treatment minimally invasive: the leakage was detected endoscopically and the defect was closed laparoscopically and covered by a fundoplication. This experience emphasises the importance of appropriate management of complications as part of the evaluation of new endoscopic methods.


Foetal pulmonary maturity in dogs: Estimated from bubble tests in amniotic fluid obtained via amniocentesis.
The goal of this study was to evaluate the reliability of amniocentesis during late pregnancy to assess lung maturity in puppies using a bubble test as described by Gunston and Davey (South African Medical Journal, 54, 1978, 495). Thirty-five bitches from eight different breeds were followed during late pregnancy before undergoing elective Caesarean (C)-section on days 61-62 after ovulation. Bubble tests were performed the day before the C-section (n = 11 bitches) and before the administration of aglepristone on amniotic fluid samples obtained via amniocentesis and were repeated the day of the surgery on amniotic fluid samples collected via puncture of the amniotic bags before they were opened (n = 35 bitches). No complications were observed following amniocenteses and the C-sections. The mortality rate (2.3%) was similar to the result of other studies using the same protocol for an elective C-section. Of the non-contaminated samples collected the day of the C-section, 89.6% were positive in the bubble test, which was consistent with observations of clinical maturity the day of the surgery and on the following days. In contrast, 70% of the samples collected the day before the C-section (when progesterone concentrations were still high) were negative, suggesting that the puppies were still immature at this point in the pregnancy. Additionally, we observed a significant difference in the bubble test results before and 18 hr after the administration of aglepristone, suggesting that aglepristone may act as an inducer of the final maturation of the puppies by inactivating progesterone receptors and simulating a physiological decrease in progesterone. Finally, we confirmed the need to exclude all contaminated samples, which could lead to false-negative results.


Efficacy and safety of docetaxel plus prednisolone chemotherapy for metastatic hormone-refractory prostate adenocarcinoma: single institutional study in Korea.
To assess the efficacy and safety of treating Korean patients with metastatic hormone-refractory prostate cancer (HRPC) using docetaxel plus prednisolone chemotherapy. This was a retrospective cohort study performed in 98 patients with metastatic HRPC between October 2003 and April 2008. After screening, 72 patients fit the eligibility criteria for inclusion in this study. Treatment consisted of 5 mg prednisolone twice daily and 75 mg/m² docetaxel once every 3 weeks. Patient demographic characteristics included: median age 67 years (range, 51~86), median ECOG performance status 1 (0~2), Gleason score ≥8 in 61 patients (86%), and median serum PSA 45.5 ng/mL (range, 3.7~2,420.0). A total of 405 cycles of treatment were administered with a median 6 cycles (range, 1~20) per patient. The median docetaxel dose-intensity was 24.4 mg/m(2)/week (range, 17.5~25.6). A PSA response was seen in 51% of 63 evaluable patients at 12 weeks and maximal PSA decline ≥50% in 59% of 70 evaluable patients. Tumor response was evaluated in 13 patients, 4 patients achieved PR, and 5 patients had SD with a response rate of 31%. With a median follow-up duration of 23.1 months (95%CI, 16.7~29.5), the median time to PSA progression was 5.1 months (95%CI, 4.5~5.8) and median overall survival was 22.8 months (95%CI, 16.6~29.1). Nine (13%) patients experienced grade 3 or higher febrile neutropenia. This chemotherapy regimen (docetaxel every 3 weeks plus prednisolone daily) demonstrated a strong response in Korean patients with metastatic HRPC, while the toxicity profile was manageable and similar to that observed in Western patients.


Impedance cardiography: a noninvasive way to monitor hemodynamics.
Impedance cardiography is a noninvasive way to measure hemodynamics and thoracic fluid status that can be quickly implemented by the nurse in any setting. This article describes the principles and use of impedance cardiography and how it can allow nurses to improve patient outcomes through early recognition of hemodynamic abnormalities.


Genetic and serological analysis of the expression of crossreactive idiotypic determinants on anti-p-azobenzenarsonate antibodies and p-azobenzenarsonate-specific suppressor T cell factors.
Data are reported on the genetic control and structure of antigen-specific suppressive molecules obtained from azobenzenearsonate (ABA)-specific suppressor T cells (Ts). Ts-derived suppressor factors (TsFs) were previously shown to bear determinants encoded by genes of the I-J subregion of the H-3 major histocompatibility complex and structures encoded by VH (variable region of heavy chains) genes linked to the Igh locus. To further characterize TsF we have made use of a K light (L) chain variable region (VK) genetic marker linked to the locus governing expression of a crossreactive idiotype on anti-ABA antibodies. The experiments evaluated the possible contribution to TsF of structures under control of the VK locus. TsF was prepared in strains of mice with known Igh and VK genes. Mice carrying Igh-1e genes produced TsF that was retained by an immunoadsorbent containing bound anti-idiotype antibodies; the genetic constitution at the VK locus was not relevant. By using a panel of anti-idiotypic antibodies prepared against the antigen-binding site of antibody carrying the idiotype, against determinants outside the site or against VH structures, we determined that idiotypic structures on the TsF are associated with V-region elements associated with the H chain and not with the binding site formed by a VH-BL combination.


Assessment of Cardiac Rate and Rhythm in Fetuses with Arrhythmia via Maternal Abdominal Fetal Electrocardiography.
Objective This study aims to report our experience using the Monica AN24 (Monica Healthcare Ltd., Nottingham, United Kingdom), a maternal transabdominal fetal electrocardiographic monitor, in a case series of fetuses with arrhythmias. Study Design We recorded fetal electrocardiograms (fECGs) on subjects with fetal arrhythmias diagnosed by fetal echocardiogram. Fetal heart rate and rhythm were determined via manual fECG analysis. Results Overall, 20 fECGs were recorded from a pool of 13 subjects. Fetal heart rate acquisition was determined to be high, medium, and poor quality in 10, 3, and 7 tracings, respectively. High-quality tracings were obtained in 9 of 11 subjects with gestational age < 26 or > 34 weeks. P waves were detectable in five tracings. Conclusion In subjects < 26 or > 34 weeks' gestational age, there was reasonable success in fetal heart rate acquisition. Further study is warranted to determine the potential role of this device in the monitoring of subjects with fetal arrhythmias.


Discovering Human Activities from Binary Data in Smart Homes.
With the rapid development in sensing technology, data mining, and machine learning fields for human health monitoring, it became possible to enable monitoring of personal motion and vital signs in a manner that minimizes the disruption of an individual's daily routine and assist individuals with difficulties to live independently at home. A primary difficulty that researchers confront is acquiring an adequate amount of labeled data for model training and validation purposes. Therefore, activity discovery handles the problem that activity labels are not available using approaches based on sequence mining and clustering. In this paper, we introduce an unsupervised method for discovering activities from a network of motion detectors in a smart home setting. First, we present an intra-day clustering algorithm to find frequent sequential patterns within a day. As a second step, we present an inter-day clustering algorithm to find the common frequent patterns between days. Furthermore, we refine the patterns to have more compressed and defined cluster characterizations. Finally, we track the occurrences of various regular routines to monitor the functional health in an individual's patterns and lifestyle. We evaluate our methods on two public data sets captured in real-life settings from two apartments during seven-month and three-month periods.


[Lymphocytic interstitial pneumonia in primary Sjögren syndrome].
Ljmphocytic interstitial pneumonia (LIP) is a rare form of interstitial pneumonia. It can occur as a idiopathic disease however most frequently associated with other diseases, particularly Sjogren syndrome. We present a 58 years old woman, with primary Sjögren syndrome who developed after 7 years interstitial lung disease. LIP was diagnosed on the basis of histological examinations of specimens obtained by open lung biopsy. Diffuse infiltrations composed of small polyclonal lymphocytes, plasma cells with reactive follicules were found. Infiltrates observed in bronchial and bronchiolar walls expanded into interlobular and alveolar septae. Prednisone in a dose of 40 mg per day was introduced and clinical, radiological, spirometric and gasometric improvement was observed. The dose of prednisone was gradually reduced but is still continued.


Studies on surface functionalized single wall carbon nanotube for electrochemical double layer capacitor application.
Surface functionalization of single wall carbon nanotubes (SWCNTs) is carried out by chemical and electrochemical oxidation in aqueous medium. Treatment of SWCNT in acid mixtures results oxygenated surface with mainly micro porous texture which shows a pseudocapacitance of 209 Fg(-1) in 1 M H2SO4 solution at a current rate of 50 mAg(-1). The SWCNT surface become slightly non-polar when treated with fuming HNO3 even in the presence of oxygenated species. Under a current rate of 50 mAg(-1), a maximum capacitance of 202 Fg(-1) is observed in 1 M Et3MeNBF4 in polycarbonate due to presence of mesopores. Electrochemical oxidation in KNO2 functionalizes the SWCNT surface with NO2 species which shows intermediate pseudocapacitance facilitating probably organization of only smaller ions along the walls of mesopores of SWCNT. The mixed acid treated SWCNTs exhibit sensibly larger capacitance of 160 Fg(-1) even at higher current rate of 5000 mAg(-1).


The Mechanism of Markovnikov-Selective Epoxide Hydrogenolysis Catalyzed by Ruthenium PNN and PNP Pincer Complexes.
The homogeneous catalysis of epoxide hydrogenolysis to give alcohols has recently received significant attention. Catalyst systems have been developed for the selective formation of either the Markovnikov (branched) or anti-Markovnikov (linear) alcohol product. Thus far, the reported catalysts exhibiting Markovnikov selectivity all feature the potential for Noyori/Shvo-type bifunctional catalysis, with either a RuH/NH or FeH/OH core structure. The proposed mechanisms of epoxide ring-opening have involved cooperative C-O bond hydrogenolysis involving the metal hydride and the acidic pendant group on the ligand, in analogy to the well-documented mechanism of polar double-bond hydrogenation exhibited by catalysts of this type. In this work, we present a combined computational/experimental study of the mechanism of epoxide hydrogenolysis catalyzed by Noyori-type PNP and PNN complexes of ruthenium. We find that, at least for these ruthenium systems, the previously proposed bifunctional pathway for epoxide ring-opening is energetically inaccessible; instead, the ring-opening proceeds through opposite-side nucleophilic attack of the ruthenium hydride on the epoxide carbon, without the involvement of the ligand N-H group. For both catalyst systems, the rate law and overall barrier predicted by density functional theory (DFT) are consistent with the results from kinetic studies.


Extrafollicular PD1 and Intrafollicular CD3 Expression Are Associated With Survival in Follicular Lymphoma.
Both microenvironment and tumor biomarkers impact outcome in follicular lymphoma (FL). We aimed to study the effect of Ki-67, CD3, CD68, and PD1 expression on outcome of FL. Forty-eight patients were included. Stained slides were visually assessed and marker expression was correlated with outcome. Both intra- and extrafollicular expression of Ki-67, CD68, and PD1 were evaluated. CD3 was evaluated only in the intrafollicular area. The median values of expression served as a cutoff point for low- and high-expression groups. High extrafollicular PD1 expression predicted superior FFTF (freedom from treatment failure) compared with low expression (5-year 52% vs. 44%, P = .04). Five-year FFTF markedly increased from 37% to 67% (P = .057) in patients with low intrafollicular CD3 expression. Our study supports the hypothesis that survival in FL depends on the immunologic cross talk between malignant cells and microenvironment; however, the specific types of cells that influence the clinical behavior of FL are still unknown.


Association of Serum Magnesium Deficiency with Insulin Resistance in Type 2 Diabetes Mellitus.
Insulin resistance (IR) is the key pathophysiological defect that leads to the development of type 2 diabetes mellitus. The purpose of this study was to estimate serum magnesium level and insulin sensitivity indices among type 2 diabetes mellitus patients and to see an association between them. This study was carried out among 38 type 2 diabetic patients and forty age and sex matched controls. Serum fasting glucose, magnesium, insulin, urea, and creatinine levels were estimated. Insulin sensitivity indices, homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) levels were calculated as per formulae. A highly significant low serum magnesium level was found in diabetic subjects as compared to the controls. Statistically significant high HOMA levels (>2.6) and low QUICKI levels (<0.33) were found among the case group. An inverse, statistically significant correlation was found between serum magnesium and fasting insulin level. A highly statistically significant inverse correlation was found between serum magnesium and HOMA level, and a positive correlation was found between serum magnesium and QUICKI level, that is, serum magnesium level decreases with increase in IR. A strong association was also found between fasting serum insulin level and insulin sensitivity indices. This study showed a lower serum magnesium level in diabetic patients compared to control. A strong association was also found between serum magnesium level and insulin sensitivity indices. For proper management of type 2 diabetes, it may, therefore, be necessary to treat hypomagnesemia in these patients.


Antibodies toward high-density lipoprotein components inhibit paraoxonase activity in patients with systemic lupus erythematosus.
Patients with systemic lupus erythematosus (SLE) have an increased incidence of vascular disease, and oxidative stress is recognized as an important feature in this condition, despite the underlying mechanisms not being fully understood. In these patients, an interaction between lipoproteins and the immune system has been suggested, but most studies have only looked at antibodies against oxidized low-density lipoproteins. This study was undertaken to determine the presence of antibodies directed against high-density lipoproteins (HDL) and to identify a possible association between these antibodies and paraoxonase (PON), an antioxidant enzyme present in HDL. Plasma from 55 patients with SLE was collected and IgG aHDL and antiapolipoprotein A-I (aApo A-I) antibodies were assessed by enzyme-linked immunosorbent assay. Standardization of the method was performed in a control population of 150 healthy subjects. Plasma levels above 5 standard deviations of the mean of the control population were considered positive. PON activity was assessed by quantification of p-nitrophenol formation (micromol/mL/min). Patients with SLE had higher titers of aHDL (P < 0.0001) and aApo A-I (P < 0.0001) antibodies, and lower PON activity (P < 0.0001) than healthy controls. There was also a direct correlation between the titers of aHDL and aApo A-I antibodies (r = 0.61; P < 0.0001). PON activity was inversely correlated with aApo A-I (P = 0.0129) antibody levels. Anti-HDL and aApo A-I antibodies from patients with high titers were isolated and subsequently incubated with human HDL. These antibodies reduced PON activity up to a maximum of 70.2% and 78.4%, respectively. This study showed the presence of aHDL and aApo A-I antibodies in patients with SLE. These antibodies were associated with reduced PON activity in plasma, and the in vitro inhibition assay confirmed a direct inhibition of the enzyme activity.


Immune deficiency in a dog with distemper.
A 16-week-old dog developed distemper 3 weeks after the 2nd of 2 vaccinations for canine distemper (CD). Symptomatic treatment was without effect and the dog was euthanatized. Prior to euthanasia, a blood sample was obtained for serologic study. The dog was found to be hypogammaglobulinemic and to have a serum-neutralization antibody titer of 1:16 to CD virus, which is considerably lower than the average 28-day response to a single CD vaccination (1:312). Histologic examination revealed absence of germinal centers in spleen and lymph nodes, generalized lymphoid depletion, and thymic hypoplasia. Comparison with primary immunodeficiencies of man and domestic animals and with CD virus-induced immune suppression led to inconclusive interpretation of these data. Thorough immune function analysis was deemed mandatory for separating primary immunodeficiency from CD virus-induced immunosuppression in dogs.


Prosthodontic management of an extreme atrophy of the mandible correlated with a prominent genial tubercle - a clinical report.
Extreme atrophy of the mandibular alveolar crest can pose a great prosthodontic challenge, especially when the genial tubercles remain as a bony projection in the floor of the mouth. This article is a clinical report on the prosthodontic management of a severe mandible atrophy correlated with a prominent genial tubercle. A complete denture was carefully designed and fabricated in order to restore both the function and esthetics of the patient.


Innate immunity and biodefence vaccines.
Host defence in vertebrates is achieved by the integration of two distinct arms of the immune system: the innate and adaptive responses. The innate response acts early after infection (within minutes), detecting and responding to broad cues from invading pathogens. The adaptive response takes time (days to weeks) to become effective, but provides the fine antigenic specificity required for complete elimination of the pathogen and the generation of immunologic memory. Antigen-independent recognition of pathogens by the innate immune system leads to the rapid mobilization of immune effector and regulatory mechanisms that provide the host with three critical advantages: (i) initiating the immune response (both innate and adaptive) and providing the inflammatory and co-stimulatory context for antigen recognition; (ii) mounting a first line of defence, thereby holding the pathogen in check during the maturation of the adaptive response; and (iii) steering the adaptive immune system towards the cellular or humoral responses most effective against the particular infectious agent. The quest for safer and more effective vaccines and immune-based therapies has taken on a sudden urgency with the increased threat of bioterrorism. Only a handful of vaccines covering a small proportion of potential biowarfare agents are available for human use (e.g. anthrax and small pox) and these suffer from poor safety profiles. Therefore, next generation biodefence-related vaccines and therapies with improved safety and the capacity to induce more rapid, more potent and broader protection are needed. To this end, strategies to target both the innate and adaptive immune systems will be required.


[Infestation with Enterobius vermicularis mimicking appendicitis].
Gastrointestinal infestation with the parasite Enterobius vermicularis is common in humans and is usually harmless. Anal pruritus is the most characteristic symptom, but the parasites can cause severe abdominal pain mimicking appendicitis. Early recognition can prevent an unnecessary appendectomy. A six-year-old girl reported to the accident and emergency department with pain in the lower right abdominal region. She was admitted and treated for suspected perforated appendix, following physical examination supplemented with an abdominal CT scan. After antibiotic treatment the symptoms disappeared as did the abscess, apart from a minor amount of residual infiltrate. She was then readmitted twice with recurrent abdominal pain without radiological evidence of an abdominal focus. We decided to conduct a diagnostic laparoscopy and an elective appendectomy à froid. During this procedure living worms were found in the appendix. Treatment with the anthelminthicum mebendazol was effective. Gastro-intestinal infestation with E. vermicularis is very common, especially in young children. This infestation is usually harmless, but can mimic appendicitis. This infestation is easily treatable with mebendazol.


Identification of pesticide transformation products in food by liquid chromatography/time-of-flight mass spectrometry via "fragmentation-degradation" relationships.
The identification of transformation products of pesticides in foodstuffs is a crucial task difficult to tackle, due to the lack of standards and scarce information available. In this work, we describe a methodology for the identification and structural elucidation of pesticide transformation products in food. The proposed strategy is based on the use of liquid chromatography electrospray time-of-flight mass spectrometry (LC/TOFMS): accurate mass measurements of (molecule and fragment) ions of interest are used in order to establish relationships between fragmentation of the parent pesticides in the instrument (in-source CID fragmentation) and possible degradation products of these pesticides in food. Examples of this strategy showing the potential of LC/TOFMS to determine unknown pesticides in food are described in two different real samples, suggesting that pesticides often are transformed into degradation products in the same fashion that they are fragmented in the instrument. Using the proposed approach and without using standards a priori, based solely on accurate mass measurements of ions and "fragmentation-degradation" relationships, we have identified two parent pesticides (amitraz and malathion) along with six degradation products, m/z 253 (N,N'-bisdimethylphenylformamidine), 163 (N-2,4-dimethylphenyl-N-methyl formamidine), 150 (2,4-dimethylformamidine), and 122 (2,4-dimethylaniline) from amitraz, and m/z 317 and 303, due to ether hydrolysis of methyl and ethyl groups from malathion. Structures for these species were proposed, and the potential of the proposed approach was critically discussed.


Lesion Imaging and Target Detection in Multiple Scattering (LITMUS) Media.
We present an ultrasound algorithm [lesion imaging and target detection in multiple scattering (LITMUS)] suited to image lesions (hypoechoic) or targets (hyperechoic) in highly complex structures. In such media, standard ultrasound imaging techniques fail to detect lesions or targets due to aberrations and the loss of linearity between propagation distance and propagation time, caused by multiple scattering of ultrasound waves. The present algorithm (LITMUS) has the capability to predict the location as well as the size of such lesions/targets by using the multiple scattered ultrasound signals to its advantage. In this experimental and computational study, we use an ultrasound linear array. Lesions/targets are embedded at varying depths inside multiple scattering media with varying density of scatterers. In the simulations, plastic scatterers are used as the source of multiple scattering in a propagation medium (water). In the experiments, melamine sponges are used, with air alveoli as the scattering source. For multiple locations along the transducer, the incoherent backscattered intensity of the backscattered signals is extracted and the linear growth of the diffusive halo over time is tracked. Sudden changes in this growth indicate the presence of a region with reduced heterogeneity, indicative of the presence of a lesion/target. This methodology is combined with a depression detection algorithm to predict the size and location of the lesion/targets with high fidelity, despite the presence of strong heterogeneity and multiple scattering.


Isolation and characterisation of bacterial colonies from seeds and in vitro cultures of Fraxinus spp. from Italian sites.
Culturable bacteria were isolated from seeds, embryos and contaminated in vitro cultures of ash (Fraxinus excelsior L., F. ornus L. and F. angustifolia L.) and were identified using morphological and molecular analyses. Fourteen morphologically distinct isolates were recovered from seeds of Fraxinus spp. 16S rDNA sequencing categorised these isolates into ten separate genera. Three strains isolated from contaminated in vitro cultures, Pantoea agglomerans, Staphylococcus succinus and Aerococcus viridans, were used for comparative analysis with isolates from seeds. Antibiotic sensitivity testing of the isolated contaminants, including phytotoxicity of antibiotics on in vitro cultures of ash, was also investigated. Phytotoxic effects on explants immersed in ampicillin or cultured on medium containing ampicillin were negligible, however tetracycline, either alone or in combination with other antibiotics, had phytotoxic effects. We conclude that ampicillin is a suitable antibiotic to limit the growth of contaminating bacteria during the in vitro culture of ash.


Application Value of the Workshop Practice Teaching Method Based on Target-Oriented Study Modules on the Internet in Orthopedic Rehabilitation.
To explore the application value of the workshop practice teaching method based on target-oriented study modules on the internet in orthopedic rehabilitation. Thirty interns (2019-2020) in the rehabilitation department of our hospital were selected as the control group, another thirty interns (2021) in the rehabilitation department of our hospital were selected as the experimental group, and their materials were retrospectively reviewed. Both groups were given the three-month practice teaching. Besides, the conventional practice teaching method was applied to the control group, and the workshop practice teaching method based on target-oriented study modules on the internet was applied to the experimental group. After the practice teaching, the united examination paper and assessment table of the rehabilitation operation process were used to evaluate the interns' scores of theoretical knowledge about orthopedic rehabilitation, scores of practical skills, and comprehensive scores of clinical practice in the two groups. The evaluation team consisting of 5 guiding experts in the scientific research office assessed the teaching quality of the two methods. Compared with the control group, the experimental group had a notably higher score of theoretical knowledge about orthopedic rehabilitation, higher score of practical skills, and higher comprehensive score of clinical practice (92.47 ± 4.81 vs. 86.43 ± 5.12, 91.30 ± 5.68 vs. 81.53 ± 7.21, and 91.88 ± 2.45 vs. 83.98 ± 4.42, P < 0.001). According to the evaluation team, the teaching quality of the experimental group was observably higher than that in the control group (P < 0.05), and there was no remarkable difference in the scores of teachers' performance between the two groups (P > 0.05). The workshop practice teaching method based on target-oriented study modules on the internet, as a high-quality "Internet+" practice teaching mode, can improve the orthopedic interns' scores of theoretical knowledge and practical operation ability and enhance their comprehensive qualities of orthopedic rehabilitation in all respects.


Single dose treatment of vaginal candidosis: comparison of clotrimazole and isoconazole.
The therapeutic efficacy of a single dose 500 mg tablet of clotrimazole was compared with two 300 mg tablets of isoconazole in an open randomised study of 100 patients with vaginal candidosis confirmed by mycological culture. One week after treatment 100% of the clotrimazole treated patients and 98% of the isoconazole treated group gave mycologically negative results. Five weeks after treatment these figures were 74% and 78% respectively, showing that both regimens were equally effective.


Implementing a comprehensive child restraint program in a pediatric hospital: an effective model.
Motor vehicle crashes remain a leading cause of death and injury to young children. Appropriate child safety seats and child safety restraints can provide life-saving protection to children riding in motor vehicles. Many children, however, travel unrestrained or improperly restrained. Consideration of appropriate child safety restraint systems for children is an important aspect of discharge planning and can provide families with the means to prevent unintentional injuries and deaths resulting from motor vehicle crashes.


[Night work as a possible risk factor for breast cancer in nurses. Correlation between the onset of tumors and alterations in blood melatonin levels].
Exposure to light-at-night, including disturbance of the circadian rhythm, possibly mediated via the melatonin synthesis and clock genes, has been suggested as a contributing cause of breast cancer. Persons who engage in nightshift work may exhibit altered nighttime melatonin levels and reproductive hormone profiles that could increase the risk of hormone-related diseases, including breast cancer. Several studies have been conducted worldwide recently to investigate the effects of factors that can disrupt circadian rhythm and alter normal nocturnal production of melatonin and reproductive hormones of relevance to breast cancer etiology. We selected 5 international study, published on well known journals and based on large numbers of subjects, and we evaluated them in order to define a state of the art of this topic. Comparing these studies we conclude that nurses who frequently attend night shifts should undergo strict and periodical breast cancer screening, since the risk is significantly increased in this population.


Physiological requirements for growth and competitiveness of Dekkera bruxellensis under oxygen-limited or anaerobic conditions.
The effect of glucose and oxygen limitation on the growth and fermentation performances of Dekkera bruxellensis was investigated in order to understand which factors favour its propagation in ethanol or wine plants. Although D. bruxellensis has been described as a facultative anaerobe, no growth was observed in mineral medium under complete anaerobiosis while growth was retarded under severe oxygen limitation. In a continuous culture with no gas inflow, glucose was not completely consumed, most probably due to oxygen limitation. When an air/nitrogen mixture (O(2)-content ca. 5%) was sparged to the culture, growth became glucose-limited. In co-cultivations with Saccharomyces cerevisiae, ethanol yields/g consumed sugar were not affected by the co-cultures as compared to the pure cultures. However, different population responses were observed in both systems. In oxygen-limited cultivation, glucose was depleted within 24 h after challenging with S. cerevisiae and both yeast populations were maintained at a stable level. In contrast, the S. cerevisiae population constantly decreased to about 1% of its initial cell number in the sparged glucose-limited fermentation, whereas the D. bruxellensis population remained constant. To identify the requirements of D. bruxellensis for anaerobic growth, the yeast was cultivated in several nitrogen sources and with the addition of amino acids. Yeast extract and most of the supplied amino acids supported anaerobic growth, which points towards a higher nutrient demand for D. bruxellensis compared to S. cerevisiae in anaerobic conditions.


An iron-promoted aldehyde-diene cyclocoupling reaction.
A stereospecific intramolecular iron tricarbonyl-promoted aldehyde-diene cyclocoupling reaction was investigated by using simple substrates 6 and more complicated substrates 30a/30b. Demetalation of the initial products converts all complexed dienes to their pure organic counterparts. In addition, the nickel-catalyzed carbonyl-ene reaction and the Prins reaction were investigated with two different substrates.


Imaging thrombi with radiolabelled anti-fibrin monoclonal antibodies.
Monoclonal antibodies which recognize fibrin but not fibrinogen can be used to detect deposits of fibrin in vivo. Recently, two monoclonal antibodies with such specificity have been created: 59D8 (raised against a synthetic heptapeptide by Hui et al.) and T2G1s (raised against a fibrin fragment by Kudryk et al.). These two antibodies appear to share the same epitope in the N-terminus of the beta chain of fibrin, a site which is not exposed in fibrinogen. In the form of radioiodinated IgG, both antibodies have been shown to bind to deposits of fibrin and induce fresh thrombi in animal models. Use of antibody fragments which retain immunoreactivity could enhance thrombus detection by (1) increasing the rate of blood disappearance and thus increasing target/background contrast, and (2) favouring renal excretion over liver uptake. Antibody fragments which have been derivatized to contain diethylenetriaminepropyleneamineoxime (DTPA) groups have been labelled with 111In and used to produce images of fresh thrombi in animal models with thrombus-to-blood ratios of greater than 7:1 and thrombus-to-muscle ratios of greater than 200:1 by 24 h post injection. Initial clinical trials of these antibodies suggest that thrombi may be visualized within the first few hours after injection, although the image quality improves with time. Shorter-lived radiolabels (such as 99Tcm) may be useful for anti-fibrin antibody fragments if adequate thrombus/background contrast can be achieved within a few hours post injection.


Design, Synthesis, and Anti-RNA Virus Activity of 6'-Fluorinated-Aristeromycin Analogues.
The 6'-fluorinated aristeromycins were designed as dual-target antiviral compounds aimed at inhibiting both the viral RNA-dependent RNA polymerase (RdRp) and the host cell S-adenosyl-l-homocysteine (SAH) hydrolase, which would indirectly target capping of viral RNA. The introduction of a fluorine at the 6'-position enhanced the inhibition of SAH hydrolase and the activity against RNA viruses. The adenosine and N6-methyladenosine analogues 2a-e showed potent inhibition against SAH hydrolase, while only the adenosine derivatives 2a-c exhibited potent antiviral activity against all tested RNA viruses such as Middle East respiratory syndrome-coronavirus (MERS-CoV), severe acute respiratory syndrome-coronavirus, chikungunya virus, and/or Zika virus. 6',6'-Difluoroaristeromycin (2c) showed the strongest antiviral effect for MERS-CoV, with a ∼2.5 log reduction in infectious progeny titer in viral load reduction assay. The phosphoramidate prodrug 3a also demonstrated potent broad-spectrum antiviral activity, possibly by inhibiting the viral RdRp. This study shows that 6'-fluorinated aristeromycins can serve as starting points for the development of broad-spectrum antiviral agents that target RNA viruses.


Discovery of a small-molecule inhibitor of specific serine residue BAD phosphorylation.
Human BCL-2-associated death promoter (hBAD) is an apoptosis-regulatory protein mediating survival signals to carcinoma cells upon phosphorylation of Ser99, among other residues. Herein, we screened multiple small-molecule databases queried in a Laplacian-modified naive Bayesian-based cheminformatics platform and identified a Petasis reaction product as a site-specific inhibitor for hBAD phosphorylation. Based on apoptotic efficacy against mammary carcinoma cells, N-cyclopentyl-3-((4-(2,3-dichlorophenyl) piperazin-1-yl) (2-hydroxyphenyl) methyl) benzamide (NPB) was identified as a potential lead compound. In vitro biochemical analyses demonstrated that NPB inhibited the phosphorylation of hBAD specifically on Ser99. NPB was observed to exert this effect independently of AKT and other kinase activities despite the demonstration of AKT-mediated BAD-Ser99 phosphorylation. Using a structure-based bioinformatics platform, we observed that NPB exhibited predicted interactions with hBAD in silico and verified the same by direct binding kinetics. NPB reduced phosphorylation of BAD-Ser99 and enhanced caspase 3/7 activity with associated loss of cell viability in various human cancer cell lines derived from mammary, endometrial, ovarian, hepatocellular, colon, prostatic, and pancreatic carcinoma. Furthermore, by use of a xenograft model, it was observed that NPB, as a single agent, markedly diminished BAD phosphorylation in tumor tissue and significantly inhibited tumor growth. Similar doses of NPB utilized in acute toxicity studies in mice did not exhibit significant effects. Hence, we report a site-specific inhibitor of BAD phosphorylation with efficacy in tumor models.


Successful treatment of oral itraconazole for infantile hemangiomas: a case series.
Infantile hemangiomas can present a therapeutic challenge to clinicians, especially when associated with severe pain and feeding difficulties. The standard therapeutic management includes corticosteroids and propranolol. However, the clinical response is not always satisfactory. We present six cases of infantile hemangiomas successfully treated with oral itraconazole approximately 5 mg/kg per day. In the first month, the red color of the lesions became a little lighter and the growth of the lesions was controlled in all cases. An obvious clinical improvement was noted in all cases during the 3-month period, with 80-100% improvement in each patient at the end of the treatment, which was judged by both their parents and the dermatologists. Compliance with treatment instructions of oral itraconazole in infants was judged to be very good. Side-effects were mild and limited. Although itraconazole can inhibit angiogenesis and tumor growth in vitro and in vivo associated with some cancers, further research is required to understand the pathogenesis of infantile hemangiomas and the mechanism of itraconazole.


PageMan: an interactive ontology tool to generate, display, and annotate overview graphs for profiling experiments.
Microarray technology has become a widely accepted and standardized tool in biology. The first microarray data analysis programs were developed to support pair-wise comparison. However, as microarray experiments have become more routine, large scale experiments have become more common, which investigate multiple time points or sets of mutants or transgenics. To extract biological information from such high-throughput expression data, it is necessary to develop efficient analytical platforms, which combine manually curated gene ontologies with efficient visualization and navigation tools. Currently, most tools focus on a few limited biological aspects, rather than offering a holistic, integrated analysis. Here we introduce PageMan, a multiplatform, user-friendly, and stand-alone software tool that annotates, investigates, and condenses high-throughput microarray data in the context of functional ontologies. It includes a GUI tool to transform different ontologies into a suitable format, enabling the user to compare and choose between different ontologies. It is equipped with several statistical modules for data analysis, including over-representation analysis and Wilcoxon statistical testing. Results are exported in a graphical format for direct use, or for further editing in graphics programs.PageMan provides a fast overview of single treatments, allows genome-level responses to be compared across several microarray experiments covering, for example, stress responses at multiple time points. This aids in searching for trait-specific changes in pathways using mutants or transgenics, analyzing development time-courses, and comparison between species. In a case study, we analyze the results of publicly available microarrays of multiple cold stress experiments using PageMan, and compare the results to a previously published meta-analysis.PageMan offers a complete user's guide, a web-based over-representation analysis as well as a tutorial, and is freely available at http://mapman.mpimp-golm.mpg.de/pageman/. PageMan allows multiple microarray experiments to be efficiently condensed into a single page graphical display. The flexible interface allows data to be quickly and easily visualized, facilitating comparisons within experiments and to published experiments, thus enabling researchers to gain a rapid overview of the biological responses in the experiments.


Increased 4-hydroxynonenal protein adducts in male GSTA4-4/PPAR-α double knockout mice enhance injury during early stages of alcoholic liver disease.
To test the significance of lipid peroxidation in the development of alcoholic liver injury, an ethanol (EtOH) liquid diet was fed to male 129/SvJ mice (wild-type, WT) and glutathione S-transferase A4-4-null (GSTA4-/-) mice for 40 days. GSTA4-/- mice were crossed with peroxisome proliferator-activated receptor-α-null mice (PPAR-α-/-), and the effects of EtOH in the resulting double knockout (dKO) mice were compared with the other strains. EtOH increased lipid peroxidation in all except WT mice (P < 0.05). Increased steatosis and mRNA expression of the inflammatory markers CXCL2, tumor necrosis factor-α (TNF-α), and α-smooth muscle actin (α-SMA) were observed in EtOH GSTA4-/- compared with EtOH WT mice (P < 0.05). EtOH PPAR-α-/- mice had increased steatosis, serum alanine aminotransferase (ALT), and hepatic CD3+ T cell populations and elevated mRNA encoding CD14, CXCL2, TNF-α, IL-6, CD138, transforming growth factor-β, platelet-derived growth factor receptor-β (PDGFR-β), matrix metalloproteinase (MMP)-9, MMP-13, α-SMA, and collagen type 1 compared with EtOH WT mice. EtOH-fed dKO mice displayed elevation of periportal hepatic 4-hydroxynonenal adducts and serum antibodies against malondialdehyde adducts compared with EtOH feeding of GSTA4-/-, PPAR-α-/-, and WT mice (P < 0.05). ALT was higher in EtOH dKO mice compared with all other groups (P < 0.001). EtOH-fed dKO mice displayed elevated mRNAs for TNF-α and CD14, histological evidence of fibrosis, and increased PDGFR, MMP-9, and MMP-13 mRNAs compared with the EtOH GSTA4-/- or EtOH PPAR-α-/- genotype (P < 0.05). These findings demonstrate the central role lipid peroxidation plays in mediating progression of alcohol-induced necroinflammatory liver injury, stellate cell activation, matrix remodeling, and fibrosis.


Risk of All-Cause Mortality in Diabetic Patients Taking β-Blockers.
To assess the relationship between use of β-blockers and all-cause mortality in patients with and without diabetes. Using data from the US National Health and Nutrition Examination Survey 1999-2010, we conducted a prospective cohort study. The study participants were followed-up from the survey participation date until December 31, 2011. We used a Cox proportional hazards model for all-cause mortality analysis. The multivariate-adjusted hazard ratios (HRs) of the participants taking β-blockers were compared with those of the participants not taking β-blockers. This study included 2840 diabetic participants and 14,684 nondiabetic participants. Compared with diabetic participants not taking a β-blocker, all-cause mortality was significantly higher in diabetic participants taking any β-blocker (HR, 1.49; 95% CI, 1.09-2.04; P=.01), taking a β1-selective β-blocker (HR, 1.60; 95% CI, 1.13-2.24; P=.007), or taking a specific β-blocker (bisoprolol, metoprolol, and carvedilol) (HR, 1.55; 95% CI, 1.09-2.21; P=.01). In addition, all-cause mortality in diabetic participants with coronary heart disease (CHD) was significantly higher in those taking beta-blockers, compared with those not taking beta-blockers (HR, 1.64; 95% CI, 1.08-2.48; P=.02), whereas that in non-diabetic participants with CHD was significantly lower in those taking beta-blockers (HR, 0.68; 95% CI, 0.50-0.94; P=.02). A propensity score-matched Cox proportional hazards model yielded similar results. Use of β-blockers may be associated with an increased risk of mortality for patients with diabetes and among the subset who have CHD.


Enhanced susceptibility to a chemical carcinogen in rats carrying MHC-linked genes influencing development (GRC).
In an approach to testing the possible relationship between embryogenesis and carcinogenesis, we examined the susceptibility of rats carrying the grc, which is an MHC-linked gene complex affecting growth and development, to the development of the cellular and biochemical changes known to be associated with the induction of cancer. Genetically related strains which differed mainly by the presence or absence of the grc were fed a diet containing 0.02% N-2-acetylaminofluorene (AAF), and the induction of gamma-glutamyltranspeptidase (GGT)-positive foci, bile-duct proliferation and oval-cell proliferation in the livers of the two groups of animals were scored. All of the rats homozygous for the grc displayed GGT-positive foci (from three to six per section) and extensive bile-duct and oval-cell proliferation. By contrast, only 27% of the animals which did not carry the grc had GGT-positive foci in the liver, and these were present in smaller numbers (from one to three per section); there was no bile-duct or oval-cell proliferation. Biochemical studies of the liver and testes showed that the grc homozygotes had the metabolic abnormalities associated with the development of cancer: increased cholesterol biosynthesis; increased DNA synthesis, as indicated by an enhanced incorporation of 3H-thymidine into DNA; stimulation of the hexose monophosphate (HMP) pathway, as indicated by increased levels of glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (6PGD); and decreased levels of circulating lipoproteins. Both the morphological response of the rats carrying the grc to feeding AAF and the biochemical abnormalities that exist in these animal are consistent with the changes which eventually lead to cancer. Thus, there appears to be a relationship in rats between aberrations in the control of growth and development, susceptibility to the chemical induction of cancer and the control of cholesterol biosynthesis.


The Efficacy of Intraoperative EEG to Predict the Occurrence of Emergence Agitation in the Postanesthetic Room After Sevoflurane Anesthesia in Children.
Emergence agitation (EA) is common after sevoflurane anesthesia, but there are no definite predictors. This study investigated whether intraoperative electroencephalography (EEG) can indicate the occurrence of EA in children. A prospective predictive study design was used. EEG-derived parameters (spectral edge frequency 95, beta, alpha, theta, and delta power) were measured at 1.0 minimum alveolar concentration (MAC) and 0.3 MAC of end-tidal sevoflurane (EtSEVO) in 29 patients. EA was evaluated using an EA score (EAS) in the postanesthetic care unit on arrival (EAS 0) and at 15 and 30 minutes after arrival (EAS 15 and EAS 30). The correlation between EEG-derived parameters and EAS was analyzed using Spearman correlation, and receiver-operating characteristic curve analysis was used to measure the predictability. EA occurred in 11 patients. The alpha power at 1.0 MAC of EtSEVO was correlated with EAS 15 and EAS 30. The theta/alpha ratio at 0.3 MAC of EtSEVO was correlated with EAS 30. The area under the receiver-operating characteristic curve of percentage of alpha bands at 0.3 MAC of EtSEVO and the occurrence of EA was 0.672. Children showing high-alpha powers and low theta powers (= low theta/alpha ratio) during emergence from sevoflurane anesthesia are at high risk of EA in the postanesthetic care unit.


Chromosomal instability induced by Pim-1 is passage-dependent and associated with dysregulation of cyclin B1.
Overexpression of the oncogenic serine/threonine kinase Pim-1 has been shown to induce chromosomal missegregation and polyploidy in prostate epithelial cell lines (1). Here we demonstrated that Pim-1-induced polyploidy develops in a passage-dependent manner in culture consistent with a stochastic mode of progression. Induction of chromosomal instability by Pim-1 was not restricted to prostate cells as it was also observed in telomerase-immortalized normal human mammary epithelial cells. Elevated levels of cyclin B1 protein, but not its messenger RNA, were evident in early passage Pim-1 overexpressing cells, suggesting that increased cyclin B1 levels contribute to the development of polyploidy. Furthermore, regulation of cyclin B1 protein and cyclin B1/CDK1 activity after treatment with anti-microtubule agents was impaired. Small interfering RNA targeting cyclin B1 reversed the cytokinesis delay but not the mitotic checkpoint defect in Pim-1 overexpressing cells. These results indicated that chronic Pim-1 overexpression dysregulates cyclin B1 protein expression, which contributes to the development of polyploidy by delaying cytokinesis.


Implementation of evidence-based parenting programs under real-world conditions: Protocol for a scoping review.
Protecting children is recognized as a public health priority and supporting parents through the implementation of evidence-based programs is a well-known strategy to achieve this. However, researchers highlight that these programs remain insufficiently implemented in real-world contexts. A knowledge gap exists between the intended implementation of evidence-based parenting programs and their actual implementation on real-world dynamics. This scoping review aims to provide a comprehensive understanding of how evidence-based parenting programs have been implemented under real-world conditions by providing a map of available evidence and identifying knowledge gaps. The overall research question is: "How have evidence-based parenting programs been implemented under real-world conditions?". The proposed scoping review follows the framework originally described by Arksey and O'Malley, Levac and colleagues, and the Joanna Briggs Institute: (1) identifying the research questions; (2) identifying the relevant studies; (3) study selection; (4) charting the data; (5) collating, summarizing, and reporting the results; (6) consultation. The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) will inform the search strategy. The results will be described in relation to the research questions and in the context of the purpose of the review. This scoping review will help to bridge the implementation gap between research evidence and its translation into practice.


Femtosecond coherent transient infrared spectroscopy of reaction centers from Rhodobacter sphaeroides.
Protein and cofactor vibrational dynamics associated with photoexcitation and charge separation in the photosynthetic reaction center were investigated with femto-second (300-400 fs) time-resolved infrared (1560-1960 cm-1) spectroscopy. The experiments are in the coherent transient limit where the quantum uncertainty principle governs the evolution of the protein vibrational changes. No significant protein relaxation accompanies charge separation, although the electric field resulting from charge separation modifies the polypeptide carbonyl spectra. The potential energy surfaces of the "special pair" P and the photoexcited singlet state P* and environmental perturbations on them are similar as judged from coherence transfer measurements. The vibrational dephasing time of P* modes in this region is 600 fs. A subpicosecond transient at 1665 cm-1 was found to have the kinetics expected for a sequential electron transfer process. Kinetic signatures of all other transient intermediates, P, P*, and P+, participating in the primary steps of photosynthesis were identified in the difference infrared spectra.


Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages.
Infection with pandemic (pdm) A/H1N1 virus induces high levels of pro-inflammatory mediators in blood and lungs of experimental animals and humans. To compare the involvement of seasonal A/PR/8/34 and pdm A/H1N1 virus strains in the regulation of inflammatory responses, we analyzed the changes in the whole-genome expression induced by these strains in macrophages and A549 epithelial cells. We also focused on the functional implications (cytokine production) of the differential induction of suppressors of cytokine signaling (SOCS)-1, SOCS-3, retinoid-inducible gene (RIG)-I and interferon receptor 1 (IFNAR1) genes by these viral strains in early stages of the infection. We identified 130 genes differentially expressed by pdm A/H1N1 and A/PR/8/34 infections in macrophages. mRNA levels of SOCS-1 and RIG-I were up-regulated in macrophages infected with the A/PR/8/34 but not with pdm A/H1N1 virus. mRNA levels of SOCS-3 and IFNAR1 induced by A/PR/8/34 and pdm A/H1N1 strains in macrophages, as well as in A549 cells were similar. We found higher levels of IL-6, TNF-α, IL-10, CCL3, CCL5, CCL4 and CXCL8 (p < 0.05) in supernatants from cultures of macrophages infected with the pdm A/H1N1 virus compared to those infected with the A/PR/8/34 strain, coincident with the lack of SOCS-1 and RIG-I expression. In contrast, levels of INF-α were higher in cultures of macrophages 48h after infection with the A/PR/8/34 strain than with the pdm A/H1N1 virus. These findings suggest that factors inherent to the pdm A/H1N1 viral strain may increase the production of inflammatory mediators by inhibiting SOCS-1 and modifying the expression of antiviral immunity-related genes, including RIG-I, in human macrophages.


A combined therapy model (individual and family) for children with sexual behavior problems.
This article describes one model from a variety of therapy methods used in the Center for the Prevention and Treatment of Sexual Aggression Among Children. The model combines family and individual therapy for children with sexual behavior problems. The frequency is of two successive individual sessions followed by one family session. The family sessions include the child and both parents, and in some cases siblings are also invited. The article specifies the importance of family therapy for this population and describes the context for appropriate interventions. It gives the characteristics of families whose children are having sexual behavior problems and who are suitable for therapy according to this model. The article deals, among other issues, with the importance of marking boundaries, talking about the fear, restructuring the family and changing behavioral patterns, and recreating communication channels.


Silica-water superstructure and one-dimensional superionic conduit in Earth's mantle.
Water in Earth's deep interior is predicted to be hydroxyl (OH-) stored in nominally anhydrous minerals, profoundly modulating both structure and dynamics of Earth's mantle. Here, we use a high-dimensional neuro-network potential and machine learning algorithm to investigate the weight percent water incorporation in stishovite, a main constituent of the subducted oceanic crust. We found that stishovite and water prefer forming medium- to long-range ordered superstructures, featuring one-dimensional (1D) water channels. Synthesizing single crystals of hydrous stishovite, we verified the ordering of OH- groups in the water channels through optical and nuclear magnetic resonance spectroscopy and found an average H-H distance of 2.05(3) Å, confirming simulation results. Upon heating, H atoms were predicted to behave fluid-like inside the channels, leading to an exotic 1D superionic state. Water-bearing stishovite could feature high ionic mobility and strong electrical anisotropy, manifesting as electrical heterogeneity in Earth's mantle.


Is B-lineage acute lymphoblastic leukemia with a mature phenotype and l1 morphology a precursor B-lymphoblastic leukemia/lymphoma or Burkitt leukemia/lymphoma?
B-lineage acute lymphoblastic leukemia (ALL) with a mature phenotype and L1 morphology is a rare condition that may pose a diagnostic and management challenge. To report our experience with 2 such unusual cases of pediatric B-lineage ALL. Morphologic, immunophenotypic, and cytogenetic features of the leukemic blast cells were reviewed in conjunction with clinical and other laboratory findings. The leukemic blast cells in both cases were small to medium with scant basophilic cytoplasm and several small inconspicuous nucleoli, characteristic of L1 lymphoblasts. Immunophenotypically, they were positive for CD19, CD22, and low-density CD20, with expression of surface immunoglobulin lambda light chain. They were negative for immature (CD34 and terminal deoxynucleotidyl transferase), myeloid, and T-cell-associated markers. Conventional cytogenetic and fluorescent in situ hybridization studies failed to demonstrate chromosomal translocations involving the c-myc gene. Both patients were treated with Children's Cancer Group ALL protocols and had good responses. B-lineage ALL with a mature phenotype, L1 morphology, and absent chromosomal translocations involving the c-myc gene is best classified and managed as precursor B-lymphoblastic leukemia/lymphoma instead of Burkitt leukemia/lymphoma.


Ultra-Fast On-Site Molecular Detection of Foodborne Pathogens Using a Combination of Convection Polymerase Chain Reaction and Nucleic Acid Lateral Flow Immunoassay.
Rapid detection and timely treatment of diseases caused by foodborne pathogens is important for improving the curative efficiency and preventing the spread of disease. In this study, we developed an assay utilizing a recently introduced ultra-fast convection polymerase chain reaction (cPCR) in conjunction with a simple nucleic acid lateral flow (NALF) immunoassay for ultra-fast on-site molecular detection of foodborne pathogens. Two Salmonella enterica serovars, Salmonella Enteritidis and Salmonella Typhimurium, and Escherichia coli O157:H7 were used as the target pathogens. We confirmed the specific amplification of the target species with specifically designed modified primer sets for cPCR in singleplex and duplex modes. After cPCR amplification, we compared the detection specificity and sensitivity using agarose gel electrophoresis and NALF assays with one or two test lines. The cPCR amplicons were readily and sensitively detected using the NALF assay, and the sensitivity was comparable with that of agarose gel electrophoresis. To confirm the application of the assay in real-life samples, the assay was used to test artificially contaminated milk. Without sample pre-enrichment, the limit of detection (LOD) was 4.5 × 103 colony-forming units (CFU)/mL for Salmonella species; 4.5 × 104 CFU/mL to differentiate Salmonella Enteritidis and Salmonella Typhimurium; and 2.3 × 103 CFU/mL for E. coli O157:H7, in a duplex assay. With a 6 h pre-enrichment, the LOD was 4.5 CFU/mL for Salmonella Enteritidis and Salmonella Typhimurium, and 2.3 CFU/mL for E. coli O157:H7. The cPCR amplification took only 14 min, and the NALF assay took ca. 5 min. The total analysis time was less than 20 min. Based on these observations, we propose that the developed assay is simple, ultra-fast, and applicable for on-site detection of foodborne pathogens.


An extract of Phyllanthus amarus protects mouse chromosomes and intestine from radiation induced damages.
We reported earlier on our preliminary study of the radioprotective effect of Phyllanthus amarus (P.amarus) in mice. P.amarus was found to inhibit the myelosuppression and elevated the levels of antioxidant enzymes in the blood and liver. In the present study we have evaluated the protective effect of P.amarus against radiation-induced changes in the intestine and mouse chromosomal damage. P.amarus at concentrations of 250 & 750 mg/Kg. b. wt were found to elevate the antioxidant enzymes in the intestine and decrease the lipid peroxidation levels. Histopathological evaluations of the intestine revealed decreased damage to intestinal cells, demonstrating that P.amarus protected the intestine. The genotoxic effects of radiation on mouse chromosomes were evaluated by assaying the micronuclei formation and chromosomal aberrations. P.amarus was found to protect the clastogenic effects of radiation as seen from decreased number of micronuclei. The administration of P.amarus was also found to decrease the percentage of chromosomal aberrations. Based on our present and previous reports it could be concluded that P.amarus extract has significant radioprotective activity.


Magnetic resonance imaging of microvascular obstruction in hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation.
The clinical significance of microvascular obstruction (MO) in hypertrophic cardiomyopathy (HOCM) after percutaneous transluminal septal myocardial ablation (PTSMA) remains unknown. To assess the relationship between the location of MO and the improvement in symptoms and pressure gradient after PTSMA in patients with HOCM. Twenty-three patients with HOCM underwent MRI within 24 weeks after PTSMA. The MO was defined visually as the hypointense region adjacent to the left or right ventricular cavity, which was surrounded by myocardial infarction. The location of MO and improvement in clinical symptoms and pressure gradient at 3-6 months follow-up were assessed. MO was observed in 16 patients who underwent MRI within 7 weeks after PTSMA. Left-sided MO was observed in 12 patients, and right-sided MO was observed in four patients. Improvement in clinical symptoms and reduction in the pressure gradient were not sufficient in the patients with right-sided MO, while PTSMA was effective in the patients with the left-sided MO. The location of MO identified by MRI may be related to the effectiveness of PTSMA at the short-term follow-up. The left-sided MO is related to complete improvement in clinical symptoms and pressure gradients.


Maternal depressive symptoms and physical intimate partner violence and children's internalizing and externalizing behaviors in Guyanese families: Mediating role of constructive conflict behavior.
Using models of risk and resilience as a guide, this study examined the mediating role of constructive conflict behaviors on the associations between maternal depressive symptoms, intimate partner violence (IPV), and child behavior problems. The nature of the mediation pathways was also examined for two groups of families, one experiencing high and another experiencing low levels of partner social support. Participants included 196 mothers and their preschool-aged children from diverse ethnic and socioeconomic backgrounds in Guyana. Constructive conflict behaviors partially mediated the link between maternal depressive symptoms and children's externalizing behaviors. Maternal depressive symptoms and physical intimate partner violence were directly related to children's internalizing behaviors. Constructive conflict behaviors were not a mediator of the association between risk factors and children's behavioral outcomes for families experiencing high or low levels of partner social support. In the context of families experiencing high partner social support, constructive conflict behaviors appeared to be more effective in reducing children's externalizing problem behaviors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Water penetration into protein secondary structure revealed by hydrogen-deuterium exchange two-dimensional infrared spectroscopy.
Two-dimensional infrared spectroscopy in conjunction with hydrogen-deuterium exchange experiments provides detailed information about solvent penetration into protein structure. Correlating the secondary-structure sensitivity of the amide I vibration and the solvent-exposure sensitivity of amide II provides a direct probe of solvent-inaccessible residues of proteins embedded in the hydrophobic core or those involved in strong hydrogen bonds in secondary structures. Distinct spectral signatures of the cross-peak region arising from the coupling of the amide I and II modes imply a significant degree of structural stability of hydrogen-bonded contacts in alpha-helices and beta-sheets in a series of proteins. Ubiquitin, an alpha/beta-protein, exhibits strong alpha-helical signatures and lacks those of the beta-sheet in the cross-peak region, demonstrating that ubiquitin's beta-sheet exchanges protons with the surrounding solvent and is conformationally unstable.


Race and the emergency department management of febrile seizures.
To determine if racial disparities exist in the management of febrile seizures in a large pediatric emergency department (ED), We performed a retrospective cross-sectional analysis of children 6 months to 6 years-old who presented to the ED with a febrile seizure over a 4-year period. Multivariate logistic regression models were built to examine the association between race and the primary outcome of neuroimaging, and secondary outcomes of hospital admission and abortive anticonvulsant prescription at ED discharge. There were 980 ED visits during the study period. Overall, 4.0% of children underwent neuroimaging and 11.1% were admitted. Of the 871 children discharged from the ED, 9.4% were prescribed an abortive anticonvulsant. There were no differences by race in neuroimaging or hospital admission. However, black children were less likely to be prescribed abortive anticonvulsants (adjusted odds ratio [aOR] 0.47; 95% confidence interval [CI]: 0.23-0.96) compared to non-black peers, when adjusting for demographic and clinical confounders. Stratification by insurance revealed that this disparity existed in Medicaid-insured patients (aOR 0.33, 95% CI: 0.14-0.78) but not in privately-insured patients. We found no racial disparities in neuroimaging or hospital admission among ED patients with febrile seizures. We did find racial disparities in our secondary outcome of abortive anticonvulsant prescription, driven primarily by individuals on Medicaid insurance. This pattern of findings may reflect the lack of standardized recommendations regarding anticonvulsant prescription, in contrast to the guidelines issued for other ED management decisions. Further investigation into the potential for treatment guidelines to reduce racial disparities is needed.


Replication of an H9N2 Avian Influenza Virus and Cytokine Gene Expression in Chickens Exposed by Aerosol or Intranasal Routes.
This study related the replication of an H9N2 avian influenza virus in chickens to the induction of host acute immune response after aerosol or intranasal inoculation with the virus. On 1, 2, 4, and 7 days postinoculation (dpi), oropharyngeal swabs and tissue specimens of trachea, lungs, spleen, and cecal tonsils were collected for quantification of viral RNA. Expression of cytokine genes in lungs, spleen, and cecal tonsils was quantified by reverse transcriptase-PCR. Virus was detected in all oropharyngeal swabs up to 4 dpi in chickens from both inoculation groups. However, virus was detected more frequently (P<0.05) and in higher titers (1-4 log difference) in specimens of trachea and lungs from the group exposed to aerosols than from the group given intranasal drops. In accord with viral replication findings, expressions of cytokine genes interleukin (IL)-1β (on 2 and 7 dpi), IL-6 (on 2 dpi), and interferon (IFN)-γ (on 2 and 4 dpi) were up-regulated to a significantly higher level (P<0.05) in lung tissue specimens from the group exposed to virus aerosol than from controls that were given saline intranasally. Only IFN-γ on 1 dpi was up-regulated (P<0.05) above that of controls in lung tissue specimens from the group given intranasal drops of virus. In comparison, replication of the virus and induction of IL-1β and IL-6 genes were limited in spleen and cecal tonsil tissue specimens from both groups of chickens inoculated with the virus. These findings indicate that virus administered in aerosols was more efficient than virus administered as intranasal drops, in infecting the lower respiratory tract and in inducing the activity of the cytokine genes. The intense respiratory infection caused by virus aerosols might increase the shedding and transmission of the H9N2 virus in chickens.


Expression of growth regulatory genes in primary human testicular neoplasms.
Seven testicular tumours of different histological type--two seminomas, two teratomas/teratocarcinomas/embryonal carcinomas, one mixed seminoma/teratoma, one Leydig cell tumour and one testicular lymphoma--were examined for the expression of four potentially growth regulatory genes by Northern blotting. Seven out of seven testicular tumours contained transcripts that hybridized with a human insulin cDNA-probe whereas only four out of seven tumours contained IGF II transcripts. One tumour contained high levels of LDL-receptor transcript whereas all seven tumours contained significant quantities of HMG-CoA-reductase mRNA.


Safe administration of S-1 after 5-fluorouracil-induced cardiotoxicity in a patient with colorectal cancer.
Cardiotoxicity is a rare but challenging complication of 5-fluorouracil (5-FU) therapy. Compared with 5-FU, after application of S-1 lower plasma levels of the cardiotoxic metabolite alpha-fluoro-beta-alanine have been reported. Evidence for safe administration of S-1 following 5-FU cardiotoxicity is limited to a case report in an Asian patient. Herein we report the first case of S-1 application after 5-FU cardiotoxicity in a Caucasian patient.A 67-year-old man with right-sided metastatic colorectal cancer and history of 5-FU cardiotoxicity had a progressive disease after 8-month therapy with irinotecan and bevacizumab. In consideration of known 5-FU cardiotoxicity, he was referred to our department for therapy counselling. We started a combination therapy with S-1, oxaliplatin and bevacizumab. The treatment was well tolerated without any cardiac problems.Our report confirms the safety of S-1 in cases of 5-FU cardiotoxicity also in a Caucasian patient.


Structural and dynamic features of Alzheimer's Abeta peptide in amyloid fibrils studied by site-directed spin labeling.
Electron paramagnetic resonance spectroscopy analysis of 19 spin-labeled derivatives of the Alzheimer's amyloid beta (Abeta) peptide was used to reveal structural features of amyloid fibril formation. In the fibril, extensive regions of the peptide show an in-register, parallel arrangement. Based on the parallel arrangement and side chain mobility analysis we find the amyloid structure to be mostly ordered and specific, but we also identify more dynamic regions (N and C termini) and likely turn or bend regions (around residues 23-26). Despite their different aggregation properties and roles in disease, the two peptides, Abeta40 and Abeta42, homogeneously co-mix in amyloid fibrils suggesting that they possess the same structural architecture.


[The effect of an extracranial occlusive lesion of the branches of the aortic arch on the status of the intracranial circulation].
Unilateral occlusion of extracranial cerebral arteries results in asymmetric intracranial flow rate against unaffected regional tissue circulation. Multiple occlusions entail reduction of intracranial circulation even in satisfactory collateral circulation. Reduction of tissue cerebral circulation occurs in well-defined occlusive processes with decompensated collateral circulation in the absence of carbogenic vascular responses. Co2 reactivity may serve a criterium of collateral circulation status and a positive prognostic sign in surgery planning.


[Aspecific and lymphocytic interstitial pneumonia in HIV infections].
The results of 115 bronchoscopic examinations and one autopsy in 105 adults with HIV-infection and pulmonary complications are presented. Whereas 51.7% of the events were caused by Pneumocystis carinii pneumonia (PCP), nonspecific interstitial pneumonitis (NIP) without evidence of an infectious or neoplastic condition was the second most frequent diagnosis in 14 patients (12.1%), four of whom exhibited features of lymphocytic interstitial pneumonia (LIP). The clinical, radiological and prognostic aspects of NIP/LIP, which are very similar to those of PCP, and the possible pathogenesis are discussed. The importance of an adequate diagnostic pulmonary workup is emphasized. We suggest classifying patients with NIP/LIP as stage IV E (CDC) and evaluating the efficacy of a treatment with azidothymidine (AZT) in a controlled clinical study.


Ventricular assist devices and anesthesia.
Ventricular assist devices (VADs) have revolutionized long-term care for patients with congestive heart failure. These patients represent about 1% of the adults in the United States, considering that heart failure is a contributing factor in more than 250,000 deaths annually. It has been estimated that about 60,000 patients per year in the United States could benefit from heart transplantation or long-term mechanical support. Because of the short supply of donor hearts for transplant, assist devices have become of great value. At least four assist devices are clinically available, and two other devices are being investigated. Because cardiopulmonary by-pass is required for implantation of these devices, anesthetizing these critically compromised patients requires extensive monitoring, skillful anesthetic management, and expert postoperative care.


Multi-Bit Nano-Electromechanical Nonvolatile Memory Cells (Zigzag T Cells) for the Suppression of Bit-to-Bit Interference.
Multi-bit nano-electromechanical (NEM) nonvolatile memory cells such as T cells were proposed for higher memory density. However, they suffered from bit-to-bit interference (BI). In order to suppress BI without sacrificing cell size, this paper proposes zigzag T cell structures. The BI suppression of the proposed zigzag T cell is verified by finite-element modeling (FEM). Based on the FEM results, the design of zigzag T cells is optimized.


Functional Improvement Following Diastasis Rectus Abdominus Repair in an Active Duty Navy Female.
Return to physical activity following childbirth can be a difficult process complicated by structural changes during pregnancy. A common problem is the development of a diastasis of the rectus abdominus (DRA), defined as a horizontal separation of the abdominus muscles at the linea alba. Recent data indicate that the greater the distance of separation of the muscle, the worse the functional ability. We describe a 24-year-old active duty U.S. Navy female G1P2 with a diagnosis of DRA. At 2 months postpartum, she was referred to physical therapy because of back pain and inability to meet baseline activities of daily living. After 4 months of physical therapy, she was unable to complete curl ups as required by U.S. Navy physical fitness standards. Abdominoplasty with imbrication of the abdominal wall diastasis was performed followed by additional physical therapy, after which she returned to baseline functioning. The restoration of functional ability postoperatively suggests there is a therapeutic indication for surgical correction of DRA. In high-functioning military patients with DRA who fail to return to baseline level of activity following a trial of physical therapy, surgical intervention should be considered to obtain the optimal functional ability.