Biogenic fish-gut calcium carbonate is a stable amorphous phase in the gilt-head seabream, Sparus aurata.
The main source of calcium carbonate (CaCO₃) in the ocean comes from the shells of calcifying planktonic organisms, but substantial amounts of CaCO₃ are also produced in fish intestines. The precipitation of CaCO₃ assists fish in intestinal water absorption and aids in whole body Ca²⁺ homeostasis. Here we report that the product formed in the intestinal lumen of the gilt-head seabream, Sparus aurata, is an amorphous calcium carbonate (ACC) phase. With FTIR spectroscopy and SEM imaging, our study shows that the fish-derived carbonates from S. aurata are maintained as a stable amorphous phase throughout the intestinal tract. Moreover, intestinal deposits contained up to 54 mol% Mg²⁺, the highest concentration yet reported in biogenic ACC. Mg is most likely responsible for stabilizing this inherently unstable mineral. The fish carbonates also displayed initial rapid dissolution when exposed to seawater, exhibiting a significant increase in carbonate concentration.


Metagenome-Assembled Genome of USCα AHI, a Potential High-Affinity Methanotroph from Axel Heiberg Island, Canadian High Arctic.
Metagenomic sequencing of active-layer cryosols from the Canadian High Arctic has yielded a nearly complete genome for an atmospheric CH4-oxidizing bacterium belonging to upland soil cluster α (USCα). This genome contains genes involved in CH4 metabolism, H2 metabolism, and multiple carbon assimilation pathways.


The use of electron microscopy for the detection of autophagy in human atherosclerosis.
The term autophagy broadly refers to a set of biological processes that mediate the clearance of damaged and/or dysfunctional subcellular structures. Central to this pathway is the formation of double-membrane vesicles that engulf cytoplasmic components and deliver them to the lysosomes. In mammalian systems, autophagy is believed to occur constitutively at basal rates but it can be also involved in a plethora of different pathological conditions. To date, however, its occurrence in human atherosclerosis remains incompletely characterized and often unappreciated probably due to technical limitations. Hitherto, the activation of autophagy in atherosclerosis has been investigated almost exclusively in both in vitro and in vivo disease models and only a few, isolated reports deal with the ultrastructural features of autophagy within human lesional tissues. By using a morphological approach, the present study demonstrated that autophagy is a recurrent feature of human atherosclerosis and occurred in all the main cell types involved in the disease. The autophagic cells were recognizable by the presence of numerous single and double-membraned autophagic structures, clearly distinguishable from the other cytoplasmic vacuoles by virtue of their electron density profiles and their content. These observations provide the first detailed description of the ultrastructural scenario of autophagy in human atherosclerosis.


MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies.
Hyperglycemia from pregestational diabetes mellitus induces neural tube defects in the developing fetus. Folate supplementation is the only effective way to prevent neural tube defects; however, some cases of neural tube defects are resistant to folate. Excess folate has been linked to higher maternal cancer risk and infant allergy. Therefore, additional interventions are needed. Understanding the mechanisms underlying maternal diabetes mellitus-induced neural tube defects can identify potential targets for preventing such defects. Despite not yet being in clinical use, growing evidence suggests that microRNAs are important intermediates in embryonic development and can serve as both biomarkers and drug targets for disease intervention. Our previous studies showed that maternal diabetes mellitus in vivo activates the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α) in the developing embryo and that a high glucose condition in vitro reduces microRNA-322 (miR-322) levels. IRE1α is an RNA endonuclease; however, it is unknown whether IRE1α targets and degrades miR-322 specifically or whether miR-322 degradation leads to neural tube defects via apoptosis. We hypothesize that IRE1α can inhibit miR-322 in maternal diabetes mellitus-induced neural tube defects and that restoring miR-322 expression in developing neuroepithelium ameliorates neural tube defects. This study aimed to identify potential targets for preventing maternal diabetes mellitus-induced neural tube defects and to investigate the roles and relationship of a microRNA and an RNA endonuclease in mouse embryos exposed to maternal diabetes mellitus. To determine whether miR-322 reduction is necessary for neural tube defect formation in pregnancies complicated by diabetes mellitus, male mice carrying a transgene expressing miR-322 were mated with nondiabetic or diabetic wide-type female mice to generate embryos with or without miR-322 overexpression. At embryonic day 8.5 when the neural tube is not yet closed, embryos were harvested for the assessment of 3 miR-322 transcripts (primary, precursor, and mature miR-322), tumor necrosis factor receptor-associated factor 3 (TRAF3), and neuroepithelium cell survival. Neural tube defect incidences were determined in embryonic day 10.5 embryos when the neural tube should be closed if there is no neural tube defect formation. To identify which miR-322 transcript is affected by maternal diabetes mellitus and high glucose conditions, 3 miR-322 transcripts were assessed in embryos from dams with or without diabetes mellitus and in C17.2 mouse neural stem cells treated with different concentrations of glucose and at different time points. To determine whether the endonuclease IRE1α targets miR-322, small interfering RNA knockdown of IRE1α or overexpression of inositol-requiring transmembrane kinase/endoribonuclease 1α by DNA plasmid transfection was used to determine the effect of IRE1α deficiency or overexpression on miR-322 expression. RNA immunoprecipitation was performed to reveal the direct targets of inositol-requiring transmembrane kinase/endoribonuclease 1α. Maternal diabetes mellitus suppressed miR-322 expression in the developing neuroepithelium. Restoring miR-322 expression in the neuroepithelium blocked maternal diabetes mellitus-induced caspase-3 and caspase-8 cleavage and cell apoptosis, leading to a neural tube defect reduction. Reversal of maternal diabetes mellitus-inhibited miR-322 via transgenic overexpression prevented TRAF3 up-regulation in embryos exposed to maternal diabetes mellitus. Activated IRE1α acted as an endonuclease and degraded precursor miR-322, resulting in mature miR-322 reduction. This study supports the crucial role of the IRE1α-microRNA-TRAF3 circuit in the induction of neuroepithelial cell apoptosis and neural tube defect formation in pregnancies complicated by diabetes mellitus and identifies IRE1α and miR-322 as potential targets for preventing maternal diabetes mellitus-induced neural tube defects.


[Synthesis and preliminary studies of O-(2-[18F] fluoroethyl)-L-tyrosine as a positron emission tomography imaging agent].
To develop a 18F-labeled amino acid, O-(2-[18F]fluoroethyl) - L-tyrosine(18F-FET), as a positron emission tomography (PET) tracer for imaging cerebral tumors. 18F-FET was synthesized. Preclinical studies including sterility, endotoxin, and toxicity tests were performed. Two brain tumor cases were studied using 18F-FET and compared with 18F-FDG. Radiochemical purity of 18F-FET was over 95% which remained stable for 6 hours. The 18F-FET injection was sterile and its endotoxin content accorded with the standards of Chinese Pharmacopoeia. The uptake of 18F-FET in the normal brain tissues was significantly lower than that of the tumor, and the images of the brain tumor were clearer than those of 18F-FDG. 18F-FET can accumulate in the tumor tissues to give high quality images. It suggests that 18F-FET may be a safe and effective tracer for brain tumor imaging.


Fourteen internal transcribed spacers in the circular ribosomal DNA of Euglena gracilis.
Cytoplasmic ribosomes from Euglena gracilis contain 16 rRNA components. These include the typical 5 S, 5.8 S and 19 S rRNAs that are found in other eukaryotes as well as 13 discrete small RNAs that interact to form the equivalent of eukaryotic 25-28 S rRNA (accompanying paper). We have utilized DNA sequencing techniques to establish that genes for all of these RNAs, with the exception of 5 S rRNA, are encoded by the 11,500 base-pair circular rDNA of E. gracilis. We have determined the relative positions of the coding regions for the 19 S rRNA and the 14 components (including 5.8 S rRNA) of the large subunit rRNA, thereby establishing that the genes for each of these rRNAs are separated by internal transcribed spacers. We conclude that sequences corresponding to these spacers are removed post-transcriptionally from a high molecular weight pre-rRNA, resulting in a multiply fragmented large subunit rRNA. Internal transcribed spacers, in positions analogous to some of these additional Euglena rDNA spacers, have been found in the rDNA of other organisms and organelles. This finding supports the view that at least some internal transcribed spacers may have been present at an early stage in the evolution of rRNA genes.


Performance enhancement of planar heterojunction perovskite solar cells by n-doping of the electron transporting layer.
Herein we report a simple n-doping method to enhance the performance of perovskite solar cells with a planar heterojunction structure. Devices with an n-doped PCBM electron transporting layer exhibit a power conversion efficiency of 13.8% with a remarkably enhanced short-circuit current of 22.0 mA cm(-2) as compared to the devices with an un-doped PCBM layer.


Primary invasive carcinoma associated with penoscrotal extramammary Paget's disease: a clinicopathological analysis of 56 cases.
To investigate the clinicopathological features, therapeutic strategies, and prognostic factors of patients with penoscrotal invasive extramammary Paget's disease (EMPD). We retrospectively collected clinical, pathological, and follow-up data of 56 men with invasive penoscrotal EMPD. Histopathological features of the primary skin lesion including tumour size, surgical margin status, depth of invasion and lymphovascular invasion were examined. The median age was 67 years and median longest diameter of lesion was 5 cm. All patients were treated with wide surgical excision and 22 patients with clinically positive regional lymph nodes underwent therapeutic regional lymph node dissection. At the end of the study, 44.6% of patients developed distant metastasis and 39.3% of patients had died from disease. Univariate analysis showed that patients with one of the following poor prognostic factors: depth of invasion of lower dermis or deeper, presence of lymphovascular invasion and regional lymph node metastasis at diagnosis, had significantly shorter cancer-specific survival time. Multivariate analysis found that depth of invasion was the only independent prognostic factor. The prognosis of invasive EMPD is significantly associated with depth of invasion, lymphovascular invasion and regional lymph node status. More aggressive therapy and more rigorous follow-up should be recommended for patients with these poor prognostic factors.


Taking a second look and zooming out: does this help with abnormality detection in chest radiography?
Diagnostic errors are common in radiology. The gestalt impression of an image refers to the rapid holistic understanding one formulates about an image and may facilitate improved diagnostic accuracy. The ability to generate a gestalt impression is typically acquired over time and is generally not explicitly taught. Our study aims to assess whether perceptual training using second look and minification technique (SLMT) can help image interpreters formulate a holistic understanding of an image and become more accurate at evaluating medical images. Fourteen healthcare trainees voluntarily participated in a perceptual training module, comparing the differences in detection of nodules and other actionable finding (OAF) on chest radiographs before and after perceptual training intervention. The experimental group received SLMT training, and the control group did not. Survey results were positive for all items, with the p-values <0.01. There was improvement in the performance in detection of nodules and OAF in both groups. However, this change was statistically significant only for OAFs in the control group (p-value <0.05) but not the experimental group. SLMT training was viewed by participants as an extremely helpful educational tool. Survey results indicated that participants felt the SLMT was a beneficial educational intervention. The experimental group's detection of nodules and OAF improved after SLMT, though not statistically significantly so, which may be related to the small sample size or lack of training effect. Perceptual training using SLMT may help as a useful educational technique, help radiologists identify abnormalities, and improve workflow.


Monitoring B cell alloresponses in rats.
Antibody-mediated rejection is a major cause of graft failure in organ transplantation. For this reason, B cell responses are of particular interest to transplantation research. Rats are important model organisms for transplant studies, but B cell alloimmune assays and B cell subset markers are poorly established in rats. We alloimmunized rats by donor blood injection using the high responder rat strain combination Brown Norway (donor) and Lewis (recipient) rats. Using splenocytes from alloimmunized and control rats, we established assays to assess allospecific B cell proliferation and the capacity to generate allospecific B memory cells and alloantibody-secreting cells after antigenic rechallenge in vitro using a mixed lymphocyte reaction. Furthermore, we defined a simple gating and sorting strategy for pre- and post-germinal center follicular B cells, as well as non-switched and switched plasmablasts. Our protocols for assessing B cell alloresponses and B cell subsets in rats may help to accelerate research into the role of B cells and manipulation of humoral alloresponses in transplant research.


Activation of dissolved molecular oxygen by Cu(0) for bisphenol a degradation: Role of Cu(0) and formation of reactive oxygen species.
In this study, Cu(0) was synthesized with NaBH4 as a reducing agent for Cu(II) and used to activate dissolved molecular oxygen (O2) under acidic conditions. The Cu(0) synthesized had much higher activity than the purchased. The roles of Cu was clarified and the formation of reactive oxygen species was discussed through direct detection for the first time. By detecting the valence change of Cu in a CuO system, Bisphenol A (BPA) was found to accelerate the transformation of Cu(II) to Cu(I). Besides, the evidence from electron spin resonance (ESR) studies and scavenging tests revealed the new roles of Cu(0) that Cu(0) could not only convert O2 to produce ·O2-, but also catalyze H2O2 to ·OH. The results from this study offer evidence of new reaction pathways in Cu-activated O2 systems and deepen understanding of the reaction between Cu species and O2.


Reasons for monitoring kinetics in safety evaluation studies.
Studies of the toxicity of a potential new drug form the basis of its preclinical safety evaluation and it is important that these toxicity studies are designed and conducted in a rational manner to permit the reliable interpretation and extrapolation of the resulting data to man. It is proposed that these objectives are more likely to be met with the support of pharmacokinetic data. Generally, toxicity studies include four groups of animals, a control group and three treated groups receiving low, intermediate and high dose levels respectively. In order to assist in the proper selection of appropriate dose levels and to increase the usefulness of the data obtained from toxicity studies, information on the following should be known. Relationship between dose level and the extent of absorption of the test compound. Effect of repeated (chronic) doses on the pharmacokinetics of the test compound. Relationship between the age of the animal and pharmacokinetics of the test compound. Relationship between the dose regimen used clinically and those used in toxicity studies.


The role of photorespiration during astaxanthin accumulation in Haematococcus pluvialis (Chlorophyceae).
Most previous studies on Haematococcus pluvialis have been focused on growth and astaxanthin accumulation. However, the relationships between photorespiration and astaxanthin accumulation have not been clarified. The purpose of this study was to examine the role of photorespiration during the process of astaxanthin accumulation in H. pluvialis. During astaxanthin accumulation, the astaxanthin content was reduced significantly when photorespiration was inhibited by its specific inhibitor, carboxymethoxylamine. The inhibition of photorespiration did not change the dry weight, chlorophyll content and OJIP transients during the incubation; however, the inhibition of photorespiration significantly decreased the photochemistry of photosystem II and total photosynthetic O2 evolution capacity. Moreover, the restriction in photorespiration was synchronized with a decrease of astaxanthin accumulation. These results suggest that the photorespiratory pathway in H. pluvialis can accelerate astaxanthin accumulation. We speculate that photorespiration can enhance astaxanthin accumulation in the following ways: (i) photorespiration directly affects the glycerate-3-phosphate (PGA) level, which is intrinsically related to the accumulation of astaxanthin in H. pluvialis; (ii) the photorespiratory pathway indirectly affects the PGA level by effecting the dark reactions of photosynthesis, which then results in the enhancement of astaxanthin accumulation in H. pluvialis.


The changing face of cardiac transplantation: the Washington University Program, 1985-1987.
Since January, 1985, 59 patients have undergone 62 heart transplantations at Washington University School of Medicine. The experience in this program serves as a useful microcosm of the field of cardiac transplantation as a whole to demonstrate certain trends that are becoming evident. Of the patients, 47% had coronary artery disease compared with 40% with cardiomyopathy. Fourteen patients (24%) were 55 years old or older at the time of transplantation. Sixteen patients (27%) required mechanical support of respiration or circulation or both prior to transplantation. Six patients were maintained with a left ventricular or biventricular assist device, and all survived; 1 patient received extracorporeal membrane oxygenation and lived; 7 patients were maintained with an intraaortic balloon pump, 6 of whom survived; and 2 were maintained with a mechanical ventilator and survived. The preoperative waiting period averaged 51 days for the group as a whole. Status-3 patients experienced an average 81-day waiting period, and those in blood group O waited 155 days. In contrast, critically ill patients (status 0) underwent transplantation within an average of 9 days. Actuarial survival at 12 months for all patients, operative survivors, patients age 55 years old or more, and patients bridged to transplantation was 87%, 92%, 84%, and 87%, respectively. Utilizing the combination therapy of cyclosporine, azathioprine, and prednisone introduced by one of us in 1983 and administered to all patients in this series, 50% of patients were rejection free and 56% were infection free at 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)


Myocardial function in early hours after coronary artery bypass grafting: comparison of two cardioplegic methods.
The theoretical advantages of retrograde blood cardioplegia combined with anterograde blood cardioplegia and warm reperfusion before aortic unclamping during coronary surgery were evaluated in 41 patients (group 2). The early postoperative myocardial function of this group was compared with that of 55 patients (group 1) in whom cold crystalloid cardioplegia was administered. The following variables were measured and analyzed by multivariate statistical analysis: heart rate, left atrial pressure, systemic arterial pressure, cardiac index, left ventricular stroke work index, ventricular function, oxygen delivery, hemoglobin, partial oxygen pressure in mixed venous blood, arteriovenous oxygen difference, carbon dioxide production per square meter, and cardiac isoenzyme of creatine-kinase. The myocardial function improved progressively and cardiac enzymatic release was low for both groups 9 hours after admission to the intensive care unit. However, group 2 had significantly higher oxygen delivery, carbon dioxide production per square meter, cardiac index, left ventricular stroke work index, and ventricular function and significantly lower left atrial pressure and mean systemic arterial pressure than that of group 1. The best separation of group 2 from group 1 occurred at the ninth hour, with a probability of correct recognition of 92.1%.


Test-Retest Reliability of the National Health and Nutrition Examination Survey's 5-Item Food Insecurity Questionnaire Completed by Fourth-Grade Children.
To examine test-retest reliability and internal consistency of a 5-item food insecurity questionnaire used in the National Health and Nutrition Examination Survey (NHANES). Researchers administered NHANES's questionnaire in the classroom to 92 fourth-grade children (74 African American; 48 girls) in 2 sessions 27-30 days apart in spring, 2011. Each classroom administration lasted 5-10 minutes. Test-retest reliability was 0.66 (Kendall tau), which is modest. Internal consistency (Cronbach alpha) was .67 and .70 for respective administrations. Food insecurity scores were related to gender (adjusted P = .05) and academic achievement (adjusted P = .004) but not to socioeconomic status or body mass index percentile (binomial regression). On average, boys reported higher food insecurity than girls. Children with lower academic achievement scores reported higher food insecurity than children with higher academic achievement scores. NHANES's 5-item questionnaire may be group administered to assess food insecurity efficiently as reported by individual fourth-grade children.


G protein-coupled receptor160 regulates mycobacteria entry into macrophages by activating ERK.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, invades and replicates within susceptible hosts by disturbing host antimicrobial mechanisms. Although G protein-coupled receptors (GPCRs) are involved in most physiological and pathological activities of mammalian cells, the roles of GPCRs in Mtb invasion into host cell remain elusive. Here, we report that GPR160 expression is elevated at both mRNA and protein level in macrophages in response to BCG infection. Both the PiggyBac (PB) transposon-mediated mutation of gpr160 gene in mouse primary macrophages and siRNA-mediated knockdown of GPR160 in the human macrophage cell line THP-1 markedly reduced the entry of green fluorescent protein (GFP) expressing BCG (BCG-GFP), also operative in vivo. BCG infection-induced phosphorylation of ERK1/2 was significantly reduced in gpr160 mutated (gpr160(-/-)) macrophages relative to levels observed in wild type macrophages, while inhibition of ERK by specific inhibitor or knockdown ERK1/2 by specific siRNA markedly reduced entry of BCG. Finally, lower bacteria burdens and attenuated pathological impairments were observed in the lungs of BCG-infected gpr160(-/-) mice. Furthermore, gpr160(-/-) macrophages also exhibits reduced uptake of Escherichia coli and Francisella tularensis. Taken together, these findings suggest an important role of GPR160 in regulating the entry of BCG into macrophages by targeting the ERK signaling pathway. As GPCRs have proven to be successful drug targets in pharmaceutical industry, it's tempting to speculate that compounds targeting GPR160, a G protein-coupled receptor, could intervene in Mtb infection.


Effects of Dietary Babassu Oil or Buriti Oil on Nutrient Intake and Total Tract Digestibility, and Abomasal Digesta Fatty Acid Profile of Lambs.
Our current understanding of the effect of medium-chain FA (MCFA) rich vegetable oils on ruminant nutrition is limited. We assessed the effects of babassu or buriti oil addition to the diet of lambs on intake, nutrient digestibility, FA profile of abomasal digesta content and biohydrogenation (BH) patterns in digestion. The experimental diets were defined by the addition of babassu oil or buriti oil to the diet, as follows: (1) non-supplemented diet (CON); (2) 40 g/kg of babassu oil (BAO, rich in C12:0); and (3) 40 g/kg of buriti oil (BUO, rich in c9 18:1), on a dry matter (DM) basis. During the last five days of the feedlot, samples of orts and feces were individually collected to determine the nutrient and FA digestibility. At the end of the experiment, animals were slaughtered, and the abomasal digesta was collected, freeze-dried and used for FA determinations conducted by gas chromatography. The BAO diet decreased the DM (p = 0.014) and nutrient intake. The lambs fed BUO had the greatest FA intake, followed by the BAO and CON diets. However, BAO increased total FA digestibility, compared with CON, but did not differ from BUO. The BAO diet extensively changed the FA composition of abomasal digesta when compared with both the CON and BUO diets. The BAO diet also increased C12:0 and C14:0, the sum of PUFA and the BH intermediates FA, including the t-10-18:1 but decreased the C18:0 in abomasal digesta. The BUO addition had the greatest total-FA and C18:0 and the lowest biohydrogenation intermediate content in abomasal digesta. The BH was less complete with the BAO diet and a large increase in t10-18:1 and of t10-/t11-18:1 ratio was observed, which indicates the occurrence of t10 possibly shifted rumen BH pathways, probably as a response to bacterial membrane stress induced by the greater C12:0 concentration in the rumen.


Factors affecting the organochlorine pollutant load in biota of a rice field ecosystem (Ebro Delta, NE Spain).
The concentrations of PCBs, DDTs, HCHs, HCB and OCS were determined in sediments and associated biota, both invertebrates (Physella acuta, Hirudo medicinalis, chironomid larvae, Hydrous pistaceus, Helochares lividus) and vertebrates (Rana perezi), in a temporary aquatic system, a rice field in the Ebro Delta (NE Spain). The qualitative and quantitative distribution of organochlorine compounds in sediments and aquatic biota has been explained by two mechanisms: equilibrium partitioning and/or biomagnification through the trophic web. Nevertheless, bioaccumulation processes are by far more complex, since several biotic and abiotic factors contribute to the observed pollutant loads in the organisms. In this respect, the biological characteristics of the organisms considered (e.g. species, age, lipid contents, feeding habits, etc.), as well as ecological factors (e.g. the habitat of the species and vertical distribution), have been shown to account for the organochlorine levels observed.


Bone formation ability of Gli1+ cells in the periodontal ligament after tooth extraction.
During the process of socket healing after tooth extraction, osteoblasts appear in the tooth socket and form alveolar bone; however, the source of these osteoblasts is still uncertain. Recently, it has been demonstrated that cells expressing Gli1, a downstream factor of sonic hedgehog signaling, exhibit stem cell properties in the periodontal ligament (PDL). Therefore, in the present study, the differentiation ability of Gli1+-PDL cells after tooth extraction was analyzed using Gli1-CreERT2/ROSA26-loxP-stop-loxP-tdTomato (iGli1/Tomato) mice. After the final administration of tamoxifen to iGli1/Tomato mice, Gli1/Tomato+ cells were rarely detected in the PDL. One day after the tooth extraction, although inflammatory cells appeared in the tooth socket, Periostin+ PDL-like tissues having a few Gli1/Tomato+ cells remained near the alveolar bone. Three days after the extraction, the number of Gli1/Tomato+ cells increased as evidenced by numerous PCNA+ cells in the socket. Some of these Gli1/Tomato+ cells expressed BMP4 and Phosphorylated (P)-Smad1/5/8. After seven days, the Osteopontin+ bone matrix was formed in the tooth socket apart from the alveolar bone. Many Gli1/Tomato+ osteoblasts that were positive for Runx2+ were arranged on the surface of the newly formed bone matrix. In the absence of Gli1+-PDL cells in Gli1-CreERT2/Rosa26-loxP-stop-loxP-tdDTA (iGli1/DTA) mice, the amount of newly formed bone matrix was significantly reduced in the tooth socket. Therefore, these results collectively suggest that Gli1+-PDL cells differentiate into osteoblasts to form the bone matrix in the tooth socket; thus, this differentiation might be regulated, at least in part, by bone morphogenetic protein (BMP) signaling.


Fumaric acid esters in necrobiosis lipoidica: results of a prospective noncontrolled study.
Necrobiosis lipoidica (NL) is an uncommon granulomatous skin disease with association to diabetes mellitus. To date, no proven effective therapy for NL has been implemented. The standard treatment is topical application of corticosteroids, but numerous agents have been reported for NL, with varying degrees of success. In recent case reports, fumaric acid esters (FAE) have been reported to be effective in granulomatous skin diseases such as granuloma annulare, cutaneous sarcoidosis and NL. We sought to investigate the efficacy of FAE in a larger number of patients with NL. Eighteen patients with histopathologically proven NL were consecutively recruited into a prospective noncontrolled study. Dosage of FAE was given according to the standard therapy regimen for psoriasis. FAE were administered for at least 6 months. The treatment outcome was evaluated by means of clinical and histological scoring and 20-MHz ultrasound assessments. Three patients discontinued therapy with FAE, while the remaining 15 patients finished the study. After a mean +/- SD treatment period of 7.7 +/- 2.9 months, a significant (P < 0.001) decrease in the mean +/- SD clinical score, from 7.4 +/- 1.8 at the beginning to 2.5 +/- 1.3 at the end of therapy, was observed. Significant clinical improvement of NL was accompanied by significant (P = 0.019) increase of dermal density as assessed by means of 20-MHz ultrasound, and significant (P = 0.011) reduction of the histological score. Adverse effects were moderate and consisted mainly of gastrointestinal complaints and flushing. During follow-up of at least 6 months, clinical outcome remained stable in all patients. The results of this study demonstrate that FAE are beneficial and safe in the treatment of patients with NL.


[Correcting the congenital ala defect of the facial cleft with revolving reposition].
To introduce the experience of correcting the congenital ala defect of facial cleft with the method of revolving reposition. Five patients were treated with this method. Based on features of the defect, two different operations were employed with the medial crura or the lateral crura of the ala as the revolving pivot. All the operations obtained good results. The operation of revolving reposition for congenital ala defect is a simple practical method with satisfactory results.


Dysregulation of metabolic pathways in pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive disorder of unknown origin and the most common interstitial lung disease. It progresses with the recruitment of fibroblasts and myofibroblasts that contribute to the accumulation of extracellular matrix (ECM) proteins, leading to the loss of compliance and alveolar integrity, compromising the gas exchange capacity of the lung. Moreover, while there are therapeutics available, they do not offer a cure. Thus, there is a pressing need to identify better therapeutic targets. With the advent of transcriptomics, proteomics, and metabolomics, the cellular mechanisms underlying disease progression are better understood. Metabolic homeostasis is one such factor and its dysregulation has been shown to impact the outcome of IPF. Several metabolic pathways involved in the metabolism of lipids, protein and carbohydrates have been implicated in IPF. While metabolites are crucial for the generation of energy, it is now appreciated that metabolites have several non-metabolic roles in regulating cellular processes such as proliferation, signaling, and death among several other functions. Through this review, we succinctly elucidate the role of several metabolic pathways in IPF. Moreover, we also discuss potential therapeutics which target metabolism or metabolic pathways.


RhoGDI-3 regulates RhoG and targets this protein to the Golgi complex through its unique N-terminal domain.
Guanine nucleotide dissociation inhibitors (GDIs) regulate both GDP/GTP and membrane association/dissociation cycles of Rho/Rac and Rab proteins.RhoGDI-3 is distinguishable from other rhoGDI proteins by its partial association with a detergent-resistant subcellular fraction. Here, we investigate the activity of this unusual rhoGDI using confocal laser scanning microscopy, immuno-isolation, and rhoGDI-3 mutants. We establish that the noncytosolic fraction of rhoGDI-3 is associated with the Golgi apparatus. The domain involved in this association is the unique N-terminal segment of rhoGDI-3 predicted to form an amphipathic alpha helix. This peptide is indispensable for Golgi association of rhoGDI-3 and sufficient to address a green fluorescent protein to the Golgi apparatus. Site-directed mutations, decreasing the hydrophobic surface of the helix, localize rhoGDI-3 into the cytoplasm. We establish that rhoGDI-3 is able to inhibit activation of the RhoG protein and to target this protein to the Golgi apparatus. Furthermore, we demonstrate the importance of the rhoGDI-3 N-terminal segment for both Golgi targeting and stability of the cytoplasmic RhoG/rhoGDI-3 complex. RhoGDI-3 is the first example of a GDI directly involved in the delivery of a Rho protein to a specific subcellular compartment.


Hydrophilic magnetic molecularly imprinted nanobeads for efficient enrichment and high performance liquid chromatographic detection of 17beta-estradiol in environmental water samples.
Novel magnetic molecularly imprinted nanobeads for 17β-estradiol (E2), namely, E2-MMINs, were synthesized by molecularly imprinted polymers on the surface of magnetic nanobeads in aqueous solvents. The hydrophilic nanobeads were set up by adopting carboxyl group-functionalized Fe3O4 nanoparticles as carriers, E2 as template molecule, and dopamine as functional monomer. The synthesized E2-MMINs were investigated in different aspects including synthesis conditions, physical and chemical properties, and adsorption conditions. The experimental results show that the E2-MMINs present not only thin imprinting layers, stable crystal form, and fast magnetic separation ability, but also rapid kinetics (20 min), high binding amount (41.48 mg g-1), satisfactory specificity (imprinting factor = 8.07), and favorable reusability (adsorption efficiency > 94.8% after reusing for 10 times). Moreover, the method employing E2-MMINs combined with high performance liquid chromatography for the specific enrichment and determination of trace E2 has been developed with the low LOD (0.008 μg L-1), and the application in environmental water samples has been proved. This work demonstrates that the proposed synthetic strategy is highly promising to the synthesis of hydrophilic nanobeads for efficient enrichment and detection of target molecule E2.


Hollow Polyhedral Arrays Composed of a Co3O4 Nanocrystal Ensemble on a Honeycomb-like Carbon Hybrid for Boosting Highly Active and Stable Evolution Oxygen.
We synthesize hollow polyhedral arrays composed of honeycomb-like nanosheets of Co3O4 nanocrystals imbedded on carbon quantum dots (CQDs)- and nitrogen-codoped carbon matrix via a facile in situ air oxidation pyrolysis for CQDs-incorporated metal-organic framework polyhedral arrays. The function of CQDs hollowing and forming porous nanosheet shells was found. The resulting hierarchical architecture displays excellent oxygen evolution reaction activity with a low overpotential of 301 mV to drive 100 mA cm-2 in 1.0 M KOH and long-playing durability in oxygen evolution. The high performance can be ascribed to its highly dispersed Co3O4 nanocrystals, CQDs and nitrogen codoping, internal cavities, and hierarchical pore system.


Near-point string: Simple method to demonstrate anticipated near point for multifocal and accommodating intraocular lenses.
We present a technique that uses a near-point string to demonstrate the anticipated near point of multifocal and accommodating intraocular lenses (IOLs). Beads are placed on the string at distances corresponding to the near points for diffractive and accommodating IOLs. The string is held up to the patient's eye to demonstrate where each of the IOLs is likely to provide the best near vision. None of the authors has a financial or proprietary interest in any material or method mentioned.


Guided plate wave scattering at vertical stiffeners and its effect on source location.
This paper examines guided wave transmission characteristics of plate stiffeners and their influence on the performance of acoustic noise source location. The motivation for this work is the detection of air leaks in manned spacecraft. The leaking air is turbulent and generates noise that can be detected by a contact-coupled acoustic array to perform source location and find the air leak. Transmission characteristics of individual integral stiffeners are measured across a frequency range of 50-400kHz for both high and low aspect-ratio rectangular stiffeners, and comparisons are made to model predictions which display generally good agreement. It is demonstrated that operating in frequency ranges of high plate wave stiffener transmission significantly improves the reliability of noise source location in the plate. A protocol is presented to enable the selection of an optimal frequency range for leak location.


Chronicity of high and low level mupirocin resistance in Staphylococcus aureus from 30 Indian hospitals.
Mupirocin is one of the most effective topically used antibiotic for the treatment of dermatitis, nasal carriage, decolonization of methicillin susceptible Staphylococcus aureus and eradication of methicillin resistant Staphylococcus aureus. Extensive use of this antibiotic has resulted in mupirocin resistance in Staphylococcus aureus which is a matter of concern. This study was conducted to evaluate the high and low level of mupirocin resistance in Staphylococcus aureus collected from various Indian hospitals. A total of 600 samples, of which 436 were pus specimens and 164 wound site swabs were collected from 30 Indian hospitals. Disc diffusion and agar dilution methods were used to test mupirocin susceptibility in methicillin resistant Staphylococcus aureus. Out of 600 Staphylococcus aureus isolates, 176 isolates (29.33%) were found to be methicillin resistant Staphylococcus aureus (MRSA). Out of 176 non-duplicate MRSA strains, 138 isolates were found to be mupirocin sensitive, 21 isolates had high level resistance whereas 17 isolates had low level resistance to mupirocin, which contributed 78.41%, 11.93% and 9.66% respectively. Multidrug resistant susceptibility was tested for all the MRSA with Cefuroxime, Cotrimoxazole and Vancomycin antibiotics. All the high and low level resistant strain were subjected to genome screening for mupA ileS gene respectively. mupA gene was found positive in all the high level resistant strain and out of 17 low level resistant strain, 16 strain were found point mutation in V588F of ileS gene. Overall, high rate of mupirocin resistance was found in the studied samples which might be a result of indiscriminate use of mupirocin in the population of studied region. This data emphasizes the urgent need for formulation of a well-defined and regulated guidelines for mupirocin use. Moreover, continuous surveillance is needed for the use of mupirocin and routine test should be performed to detect MRSA in patients and health care personnel to prevent MRSA infections.


MiR-16 family as potential diagnostic biomarkers for cancer: a systematic review and meta-analysis.
Cancer is a main public health problem all over the world with its high morbidity and mortality. MicroRNA-16 (miRNA-16, miR-16) family members have been considered as potential biomarkers in cancer diagnosis in several previous studies, but their results were inconsistent. The present meta-analysis was conducted to assess the diagnostic efficacy of miR-16 family for cancer systematically. Multiple search strategies and random-effects model were used. Pooled sensitivity, specificity and other parameters were calculated. Totally, 1,259 cancer patients and 855 controls from 16 articles were enrolled in this meta-analysis. The pooled results for sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR) and the area under the curve (AUC) were 0.80 (95% CI: 0.73-0.85), 0.77 (95% CI: 0.70-0.84), 3.5 (95% CI: 2.5-5.0), 0.26 (95% CI: 0.19-0.36), 14 (95% CI: 8-25) and 0.86 (95% CI: 0.82-0.88), respectively. Our subgroup analyses indicated miR-16 family assay was more appropriate in Asian populations. Our findings demonstrated that miR-16 family members have a relatively high value as promising biomarkers in diagnosing cancers. Nevertheless, the clinical application of miR-16 family profiling for cancers diagnosis still needs further large-scale studies and additional improvements of substantiation.


Computational Methods for Structural and Functional Studies of Alzheimer's Amyloid Ion Channels.
Aggregation can be studied by a range of methods, experimental and computational. Aggregates form in solution, across solid surfaces, and on and in the membrane, where they may assemble into unregulated leaking ion channels. Experimental probes of ion channel conformations and dynamics are challenging. Atomistic molecular dynamics (MD) simulations are capable of providing insight into structural details of amyloid ion channels in the membrane at a resolution not achievable experimentally. Since data suggest that late stage Alzheimer's disease involves formation of toxic ion channels, MD simulations have been used aiming to gain insight into the channel shapes, morphologies, pore dimensions, conformational heterogeneity, and activity. These can be exploited for drug discovery. Here we describe computational methods to model amyloid ion channels containing the β-sheet motif at atomic scale and to calculate toxic pore activity in the membrane.


Correlation of serum biochemical characteristics and ABCG8 genetic variant (rs 11887534) with gall stone compositions and risk of gallstone disease in Egyptian patients.
The overexpression of the cholesterol transporter: ATP-binding cassette transporter (ABCG8) due to the effect of ABCG8 genetic variant (rs11887534) leads to the precipitation of cholesterol crystals and gallstone disease (GSD). To evaluate the chemical composition of gallstones and the role of ABCG8 (rs11887534) in the susceptibility to GSD. We enrolled 77 patients with GSD treated with standard laparoscopic or open cholecystectomy and 75 age and sex-matched healthy controls. Chemical analysis of the extracted gallstones was performed. Analysis of the rs11887534 was performed by real-time PCR TaqMan technique for both cases and controls. Pure cholesterol stones were the main type of stones in GSD patients. The CC genotype carriers of rs11887534 were more prone to gallstone formation than other genotypes. The CC genotype carriers were 100 folds at increased risk to develop pure cholesterol stones. The most prevalent type of gallbladder stones is pure cholesterol stone. ABCG8 (rs11887534) could be associated with increased risk for cholesterol gallstones formation, this risk was more pronounced in female patients.


The role of spirituality and religiosity on suicidal ideation of homeless people in a large Brazilian urban center.
Suicidal ideation is an important mental health issue among homeless people. Despite the fact that spirituality and religiousness (S/R) have been associated with lower levels of suicide behavior, there is little evidence on this relationship among homeless individuals. Thus, this study aims to investigate the association between S/R and suicidal ideation among homeless people living in a large Brazilian city. This cross-sectional study included 456 homeless individuals living in Sao Paulo, Brazil. Logistic and linear regression models were used to determine the role of religious and spiritual beliefs (Duke Religion Index, FACIT SP-12 and Brief-RCOPE) on suicidal ideation, after adjustements. Most participants were male (75%) with a mean age of 44.53(SD 12.62) years. A total of 49.6% had significant depressive symptoms and the prevalence of suicidal ideation was 29.8%. In the adjusted logistic regression, higher levels of religiousness (organizational, nonorganizational and intrinsic), positive religious/spiritual coping, peace and meaning were associated with a lower suicidal ideation. The same results were found when using linear regression models. Long questionnaires can be factors of inhibition and fatigue for the participants. Suicidal ideation was based on a single question. Our results revealed a high prevalence of suicidal ideation and depression in our sample. Religiousness and spirtuality were important factors in the life of homeless individuals, being negatively associated with suicidal ideation. These results could make healthcare professionals aware of the importance of addressing S/R issues in this vulnerable population.


BIRC2/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency.
Combination antiretroviral therapy (ART) is able to suppress HIV-1 replication to undetectable levels. However, the persistence of latent viral reservoirs allows for a rebound of viral load upon cessation of therapy. Thus, therapeutic strategies to eradicate the viral latent reservoir are critically needed. Employing a targeted RNAi screen, we identified the ubiquitin ligase BIRC2 (cIAP1), a repressor of the noncanonical NF-κB pathway, as a potent negative regulator of LTR-dependent HIV-1 transcription. Depletion of BIRC2 through treatment with small molecule antagonists known as Smac mimetics enhanced HIV-1 transcription, leading to a reversal of latency in a JLat latency model system. Critically, treatment of resting CD4+ T cells isolated from ART-suppressed patients with the histone deacetylase inhibitor (HDACi) panobinostat together with Smac mimetics resulted in synergistic activation of the latent reservoir. These data implicate Smac mimetics as useful agents for shock-and-kill strategies to eliminate the latent HIV reservoir.


[Paget disease of maxillofacial localization. Clinical case and review of the literature].
Paget's disease is a chronic osteopathy of unknown origin affecting principally the long bones of body. One of those cases is here reported localized in this area, with favorable answer to medical treatment. Perusal of literature about this subject.


Spirobipyridopyrans, spirobinaphthopyrans, indolinospiropyridopyrans, indolinospironaphthopyrans and indolinospironaphtho-1,4-oxazines: synthesis, study of X-ray crystal structure, antitumoral and antiviral evaluation.
The novel racemic indolinospirobenzopyrans (5-7), indolinospironaphthopyrans (11-14) and indolinospironaphtho-1,4-oxazine (17) were synthesized by an aldol type of condensation of 1',3',3'-trimethyl-2 '-methyleneindoline and its 5-substituted derivatives with an appropriately substituted hydroxybenzaldehyde, hydroxynaphthaldehyde or nitrosonaphthol. An unequivocal proof of the stereostructures of 9 and 17 was obtained by the single-crystal X-ray diffraction method. A substituted indoline ring and the benzopyran ring in 9 and the naphtho-1,4-oxazine moiety in 17 are interconnected via the common chiral atom and positioned almost perpendicularly to each other. The five-membered 2,3-dihydropyrrolo moiety of the indoline ring adopts an envelope conformation in both structures. Of all the compounds of this series, spirobipyridopyran (1) inhibited specifically the growth of human melanoma (HBL) (IC(50): 0.9 microM) cells but not the growth of normal fibroblasts (WI38). Indolinospirobenzopyrans (8-10) showed significant cytostatic activities against all tumor cell lines. However, these compounds also exhibited a cytotoxic effect on normal human fibroblasts. The indolinospirobenzopyrans 4, 6-8, 10 and the indolinospironaphtho-1,4-oxazine 16 showed, albeit modest, selectivity as antiviral agents against varicella-zoster virus (VZV) and/or cytomegalovirus (CMV) (EC(50) within the concentration range of 1.0-12.6 microM).


2,3'-disubstituted-2-(2'-carboxycyclopropyl)glycines as potent and selective antagonists of metabotropic glutamate receptors.
2-(9-Xanthylmethyl)-2-(2'-carboxycyclopropyl) glycine 6e is a novel metabotropic glutamate receptor antagonist. A series of alpha, C-3' disubstituted (carboxycyclopropyl)glycines 6f-n were prepared. Antagonist activity was observed for all these compounds at group 2 and group 3 mGluRs. Although they were slightly less active on group 2 mGluRs than non C-3' substituted 6e, the compounds 6f-n were more selective with lesser or no activity on group 1 mGluR subtypes (IC50 values greater than 100 microns).


In vivo treatment with anti B-220 monoclonal antibody affects T and B cell differentiation.
The B220 cell marker is expressed on B cells and on T cell precursors. In order to determine the involvement of the B220 antigen on murine lymphoid differentiation, we treated 5-10-week-old mice periodically with a specific anti-B220 antibody, RA3-6B2, a non-cytolytic IgG2b. After the third injection, a significant reduction (P less than 0.02) in the number of thymocytes and less dramatically in the number of splenocytes was observed. This reduction was predominantly due to a decrease of cells carrying the following markers: Thy-1.2+, Lyt-1+, Lyt-2.3+, L3T4+, and asGM1+. Mitogenic response to concanavalin A, phytohaemagglutinin and lipopolysaccharide, mixed lymphocyte reaction, cytotoxic T cell activity, and plaque-forming cell generation were significantly decreased after the treatment (P less than 0.01). These results show that the in vivo treatment with anti-B220 monoclonal antibody reduced the number of T and B cells and modified their functional activity. This suggests that the B220 antigen is involved in the maturation of both T and B cells.


Thoracic Aortic Injuries Following Intra-Aortic Balloon Pump Placement: A Retrospective Case Series.
Thoracic aortic injuries from intra-aortic balloon pump (IABP) are rare, and no publications exist in the context of patients awaiting heart transplantation. We present a single-institution case series involving five patients out of 107 who sustained thoracic aortic injuries following IABP placement awaiting heart transplantation. The goal of this study is to describe the characteristics of patients, presenting symptoms, treatment and the impact of these injuries on their suitability for transplantation. Retrospective, single-institution study through chart review of five patients with known thoracic aortic injuries following IABP placement awaiting heart transplant. Tertiary care academic teaching hospital with all patients requiring cardiac ICU admission. All five patients were diagnosed with advanced heart failure awaiting heart transplantation. Each patient had an IABP placed while awaiting transplant. Five patients (4.6%) out of a total of 107 supported with IABP awaiting heart transplantation were identified with thoracic aortic injury. Three underwent transplantation and subsequently received thoracic endovascular aortic repair, and they are doing well with a mean follow-up of 6 months. One patient died acutely and the other did not require intervention. IABP-related aortic injuries may be more common in patients awaiting transplantation and that endovascular therapy is a suitable treatment modality with no immediate impact on transplantation outcomes. Pooled data from multiple centers may help identify patients risk profile to potentially design an algorithm that can more quickly identify these injuries.


Glycated hemoglobin and risk of death in diabetic patients treated with hemodialysis: a meta-analysis.
Studies investigating the association between glycated hemoglobin (HbA1c) level and mortality risk in diabetic patients receiving hemodialysis have shown conflicting results. We conducted a systematic review and meta-analysis using MEDLINE, EMBASE, Web of Science, and the Cochrane Library. Diabetic patients on maintenance hemodialysis therapy. Observational studies or randomized controlled trials investigating the association between HbA1c values and mortality risk. Study authors were asked to provide anonymized individual patient data or reanalyze results according to a standard template. Single measurement or mean HbA1c values. Mean HbA1c values were calculated using all individual-patient HbA1c values during the follow-up period of contributing studies. HR for mortality risk. 10 studies (83,684 participants) were included: 9 observational studies and one secondary analysis of a randomized trial. After adjustment for confounders, patients with baseline HbA1c levels ≥ 8.5% (≥ 69 mmol/mol) had increased mortality (7 studies; HR, 1.14; 95% CI, 1.09-1.19) compared with patients with HbA1c levels of 6.5%-7.4% (48-57mmol/mol). Likewise, patients with a mean HbA1c value ≥ 8.5% also had a higher adjusted risk of mortality (6 studies; HR,1.29; 95% CI, 1.23-1.35). There was a small but nonsignificant increase in mortality associated with mean HbA1c levels ≤ 5.4% (≤ 36 mmol/mol; 6 studies; HR, 1.09; 95% CI, 0.89-1.34). Sensitivity analyses in incident (≤ 90 days of hemodialysis) and prevalent patients (>90 days of hemodialysis) showed a similar pattern. In incident patients, mean HbA1c levels ≤ 5.4% also were associated with increased mortality risk (4 studies; HR, 1.29; 95% CI, 1.23-1.35). Observational study data and inability to adjust for diabetes type in all studies. Despite concerns about the utility of HbA1c measurement in hemodialysis patients, high levels (≥ 8.5%) are associated with increased mortality risk. Very low HbA1c levels (≤ 5.4%) also may be associated with increased mortality risk.


Fused in sarcoma (FUS) interacts with the cytolinker protein plectin: implications for FUS subcellular localization and function.
Fused in sarcoma (FUS) is a multifunctional protein involved in transcriptional control, pre-mRNA processing, RNA transport and translation. The domain structure of FUS reflects its functions in gene regulation and its ability to interact with other proteins, RNA and DNA. By use of a recombinant fragment of FUS in pull-down experiments followed by mass spectrometry analysis we have identified a novel interaction between the FUS N-terminal and the cytolinker plectin. An in situ proximity ligation assay confirmed that FUS-plectin interactions take place in the cytoplasm of cells. Furthermore, plectin deficient cells showed an altered subcellular localization of FUS and a deregulated expression of mRNAs bound to FUS. Our results show that plectin is important for normal FUS localization and function. Mutations involving FUS are causative factors in sarcomas and leukemias and also hereditary forms of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Plectin deficiency causes epidermolysis bullosa, a disease involving the skin and neuromuscular system. The novel FUS-plectin interaction offers new perspectives for understanding the role of FUS and plectin mutations in the pathogenesis of these diseases.


Metabolic rate, evaporative water loss and thermoregulatory state in four species of bats in the Negev desert.
Life in deserts is challenging for bats because of their relatively high energy and water requirements; nevertheless bats thrive in desert environments. We postulated that bats from desert environments have lower metabolic rates (MR) and total evaporative water loss (TEWL) than their mesic counterparts. To test this idea, we measured MR and TEWL of four species of bats, which inhabit the Negev desert in Israel, one species mainly restricted to hyper-arid deserts (Otonycteris hemprichii), two species from semi-desert areas (Eptesicus bottae and Plecotus christii), and one widespread species (Pipistrellus kuhlii). We also measured separately, in the same individuals, the two components of TEWL, respiratory water loss (RWL) and cutaneous evaporative water loss (CEWL), using a mask. In all the species, MR and TEWL were significantly reduced during torpor, the latter being a consequence of reductions in both RWL and CEWL. Then, we evaluated whether MR and TEWL in bats differ according to their geographic distributions, and whether those rates change with Ta and the use of torpor. We did not find significant differences in MR among species, but we found that TEWL was lowest in the species restricted to desert habitats, intermediate in the semi-desert dwelling species, and highest in the widespread species, perhaps a consequence of adaptation to life in deserts. Our results were supported by a subsequent analysis of data collected from the literature on rates of TEWL for 35 bat species from desert and mesic habitats.


A novel array of chemiluminescence sensors for sensitive, rapid and high-throughput detection of explosive triacetone triperoxide at the scene.
Triacetone triperoxide (TATP) is relatively easy to make and has been used in various terrorist acts. Early but easy detection of TATP is highly desired. We designed a new type sensor array for H2O2. The unique CL sensor array was based on CeO2 nanoparticles' membranes, which have an excellent catalytic effect on the luminol-H2O2 CL reaction in alkaline medium. It exhibits a linear range for the detection of H2O2 from 1.0×10(-8) to 5.0×10(-5)M (R(2)=0.9991) with a 1s response time. The detection limit is 1.0×10(-9)M. Notably, the present approach allows the design of CL sensor array assays in a more simple, time-saving, long-lifetime, high-throughput, and economical approach when compared with conventional CL sensor. It is conceptually different from conventional CL sensor assays. The novel sensor array has been successfully applied for the detection of TATP at the scene.


Intracellular citrate or externaly applied tetraethylammonium ions produce calcium-dependent action potentials in an insect motoneurone cell body.
1. Electrophysiological observations have been made upon the cell body of an identified motoneurone of the cockroach, Periplaneta americana. Normal responses were compared with those observed after intracellular injection of citrate anions or when the preparation was bathed in solutions containing tetraethylammonium ions (TEA+).2. Normally when depolarized, the motoneurone soma gave a series of damped oscillations; the amplitude of these responses increased with increase in the applied current.3. After citrate ions had been injected into the neurone soma, all-or-none action potentials were evoked by depolarization; such responses appeared about 5-10 min after the onset of citrate injection. Injection of EGTA produced similar effects. Citrate and EGTA probably produce their effect through a reduction in the intracellular free calcium concentration.4. When preparations were bathed in saline solution containing 50 mM-TEA+, soma depolarization produced prolonged all-or-none action potentials (up to approximately 100 msec duration).5. The action potentials produced by citrate injection or externally applied TEA+ appeared to have a similar ionic mechanism; they were not depressed by sodium-free solutions or by tetrodotoxin (4 x 10(-6)M) but were reversibly blocked in saline solution containing 40 mM-manganous chloride.6. The overshoot amplitude of action potentials recorded after injection of citrate anions or in solutions containing TEA+ showed a 22.5 mV change for a ten-fold change in the external calcium concentration.7. Both intracellular citrate and external TEA+ caused a significant increase in the input resistance and membrane time constant of the motoneurone.8. It is concluded that action potentials generated under various experimental conditions in the soma of this insect motoneurone map have differing ionic mechanisms.


Safety and efficacy of new glyceryl trinitrate suppository formula: first double blind placebo-controlled clinical trial.
This study was designed to assess the safety and efficacy of 0.2 percent glyceryl trinitrate suppository form in the healing of chronic anal fissure. Thirty-four patients with symptomatic chronic anal fissures were assigned to 0.2 percent glyceryl trinitrate suppository (n = 21) or placebo (n = 13) in a double blind design. Patient's symptom scores were registered at first visit. A validated daily chart was given to assess their symptoms on a daily basis. Both groups received psyllium from the beginning of the study. They were assessed at two-week intervals for six weeks. Then, they started a washout period of one month and after that were crossed over for another six weeks. Chi-squared, t-tests, and analysis of variance were used for statistical analysis. Complete healing at six weeks was achieved in 12 of 21 patients (57 percent) in the glyceryl trinitrate group and 5 of 13 patients (38 percent) in the placebo (P < 0.05). The overall healing rates at the end of study were 15 of 21 (71 percent) vs. 11 of 13 (84 percent) in the glyceryl trinitrate and placebo groups, respectively (P > 0.05). Application of 0.2 percent glyceryl trinitrate suppository form represents a new, promising, and effective treatment for chronic anal fissure.


Contraceptive and molecular function of a novel recombinant vaccine based human leukemia inhibitory factor on Balb/c mice: An experimental in vivo study.
The functional competence of leukemia inhibitory factor (LIF), as immunocontraceptive vaccine in mice, was investigated. Balb/c mice were divided into two groups of vaccinated and controls. The recombinant human LIF (rhLIF) protein and phosphate buffer saline was emulsified with Freund's adjuvant and injected into vaccinated and control groups, respectively. Theinhibition of implantation was evaluated in mice uterine. The concentration of secreted interferon-γ (IFN-γ) and interleukin (IL)-4 were measured in cultured splenocyte of mice stimulated by rhLIF. The expressions of immune responsive gene 1 (IRG-1), cochlin (COCH), amphiregulin(Ar), and heparin-binding EGF-like growth factor (HB-EGF) genes were determined. Mice were assessed for inhibition of fertility after delivery, reversibility of immune response against rhLIF, and survival rate. Active immunization of mice with rhLIF resulted in reduction of the implantation and fertility rate up to 80.49% and 75%, respectively. All mice produced a high titer of anti-rhLIF antibodies in serums and vaginal fluids washes after 16 weeks; however, these antibodies were cleared from vaginal fluid washes after six months. A significant down-regulation in mRNA levels of IRG-1, Ar and HB-EGF was observed in vaccinated group compared to controls; however, no significant change in the expression profile of cochlin gene was detected. The results showed that rhLIF prevented pregnancy in a high percentage of female mice. Although the immunization of female Balb/c mice with rhLIF inhibited fertility and expression of genes associated with this molecule, further studies are needed to support this protein as a suitable candidate for contraceptive vaccine in mammals.


Adapalene in the treatment of African patients.
To assess the efficacy and safety of topical adapalene gel 0.1% as a treatment for acne vulgaris in black South African patients. African and other darker skin types represent a particular clinical challenge for dermatologists treating acne. In many cases, this is due to the higher risk of postinflammatory hyperpigmentation in patients with dark skin. Acne vulgaris is an extremely common dermatological problem among Africans and people of African descent worldwide. Few studies of any of the major acne therapies have been carried out in exclusively black populations, and relatively little is known about the specific responsiveness of black skin to these agents. The ideal acne treatment for black people would specifically target the inflammatory process, which so often results in hyperpigmentation. Topical retinoids do this to some degree, but they can be highly irritating and this in itself can provoke post-treatment hyperpigmentation. An open-label study of adapalene 0.1% gel in 65 black South Africans, aged 12-30, for 12 weeks. Patients all had mild to moderate facial acne as defined by the Leeds scoring system; they were instructed to apply the medication once daily. Lesion counts and severity scores were assessed at 4, 8 and 12 weeks. A total of 44 subjects completed the trial and all three follow-up visits. Adapalene gel 0.1% showed clear efficacy against both inflammatory and non-inflammatory lesions. The drop in mean total facial-lesion count ranged from 46 to 72% between the first and last visit, and in most cases, there was clear improvement in cosmesis. In two-thirds of cases, patients experienced reductions in both number of hyperpigmented macules and density of hyperpigmentation. Adapalene gel 0.1% is an effective, well-tolerated topical therapy for black patients. It is able to reduce both inflammatory and non-inflammatory lesions, as well as prevent and alleviate acne-associated hyperpigmentation.


Neuron-specific enolase and S-100 protein immunohistochemistry for defining the structure and topographical relationship of the different enteric nerve plexuses in the small intestine of the pig.
The morphological and topographical features of the intramural enteric nervous system in the small intestine of the pig has been studied on whole mounts by means of neuron-specific enolase (NSE) and S-100 protein immunohistochemistry. A clear visualization of the myenteric plexus allows the recognition of its characteristic morphology, including the thin tertiary plexus coursing within the smooth muscle layers. In the tela submucosa two ganglionated plexuses, each with its own specific characteristics, can clearly be demonstrated: (1) the plexus submucosus externus (Schabadasch) located near the inner surface of the circular muscle layer at the abluminal side of the submucosal vascular arcades, and (2) the plexus submucosus internus (Meissner) close to the outer surface of the lamina muscularis mucosae at the luminal side of the submucosal vascular arcades. Due to the possibility to trace clearly the perivascular plexuses of these vascular arcades by use of immunohistochemical techniques with antibodies to NSE and S-100 protein, the two submucosal nerve plexuses can be demonstrated with exceptional clarity. This is the first report of an investigation of the intramural nerve plexuses of the small intestine of the pig using the NSE and S-100 immunostaining methods, which is sufficiently detailed to substantiate the characteristic topography and structure of the two submucosal plexuses and their relation to the smooth muscle layers and perivascular plexuses. The level of NSE immunoreactivity for enteric neurons displays great variation, a substantial proportion of the type-II neurons appearing strongly stained. Although little is known of the specific function of these enzymes, proposals are discussed.


Multiple electrical breakdowns and electrical annealing using high current approximating breakdown current of silver nanowire network.
The failure of a silver nanowire (AgNW) random network due to high electric current density is described. The AgNW network breaks down as result of electromigration and Joule heating at junctions, which leads to destroyed interconnections between AgNWs. The AgNW network is not completely destroyed after breakdown, but instead is able to undergo multiple breakdowns after being cooled down, with increased resistance and reduced breakdown current density. The breakdown current density of AgNW network is J(max) = 25 A cm(-2) for a network with R(s) ~ 40 Ω sq(-1) outperforming a CuNW network. An effective electrical annealing method is demonstrated to decrease network resistance by 18% by periodically applying high current that is slightly lower than breakdown current with a period of 1 min for a few cycles.


Repeated brief social defeat episodes in mice: effects on cell proliferation in the dentate gyrus.
Stressful experiences can affect hippocampal structure and function and can suppress new cell birth in the adult hippocampus in several species. Here we examine how repeated intermittent social defeat affects cell proliferation in the dentate gyrus (DG) in mice. Adult male CFW mice were subjected to 10 daily social defeat episodes, 3 defeat episodes within one day or a single defeat episode. Intruder mice were injected with 5-bromo-2'-deoxyuridine (BrdU, 200mg/kg, i.p.) 1h after the last fight, and incorporation of BrdU into proliferating cells in the DG was quantified. In a third experiment, aggressive resident mice were allowed to fight with an intruder mouse every day for 10 days, and these residents were injected with BrdU 1h after the last aggressive encounter. There was a significant decrease in cell proliferation in mice that received 10 social defeats, confirming and extending earlier results. This decrease is correlated with the intensity of the defeat experiences, as quantified by frequency of attack bites. Cell proliferation was slightly inhibited after a single defeat, although this effect was not significant. Three defeats within a 5-h period had no effect on levels of proliferation. Offensive aggressive stress in the residents did not result in any changes in hippocampal cell proliferation. These data indicate that repeated intermittent social defeat experienced over multiple days suppresses proliferation in the DG, and this may have important implications for our understanding of hippocampal changes related to stress psychopathologies.


Expression and protease activity of mouse legumain are regulated by the oncogene/transcription co-activator, DJ-1 through p53 and cleavage of annexin A2 is increased in DJ-1-knockout cells.
Legumain (EC 184.108.40.206) is an asparaginyl endopeptidase. Strong legumain activity was observed in the mouse kidney, and legumain was highly expressed in tumors. We previously reported that bovine kidney annexin A2 was co-purified with legumain and that legumain cleaved the N-terminal region of annexin A2 at an Asn residue in vitro and in vivo. Recently, we found that transcription of the legumain gene is regulated by the p53 tumor suppressor in HCT116 cells. We and others reported that DJ-1/PARK7, a cancer- and Parkinson's disease-associated protein, works as a coactivator to various transcription factors, including the androgen receptor, p53, PSF, Nrf2, SREBP and RREB1. In this study, we found that expression levels of legumain mRNA and protein and legumain activity were increased in DJ-1-knockout cells. Furthermore, we found that DJ-1 binds to the p53-binding site on intron 1 of the mouse legumain gene in wild-type cells and that cleavage of annexin A2 was increased in DJ-1-knockout cells. These results suggest that legumain expression and activation and cleavage of annexin A2 are regulated by DJ-1 through p53.


Small biotechs versus large pharma: Who drives first-in-class innovation in oncology?
There is a narrative that large pharma relies on biotech and academia for drug innovation. We tested this thesis by identifying the originators of all 50 first-in-class (FIC) oncology drugs that were approved by the FDA from 2010 through 2020. Overall, the numbers support the narrative: large pharma was the sole originator of only 14% of FIC cancer drugs, whereas small biotechs originated 46%, and academic labs 14%. However, origins tell an incomplete story: large pharma companies launched or were involved in launching 76% of FIC cancer drugs. Moreover, three of the five top-selling FIC oncology drugs had large pharma origins. Thus, although biotechs and academia do originate more drugs, large pharma remains important in shepherding drugs through clinical development and approval, and in originating high-impact novel therapies.


Colour vision in retinitis pigmentosa. Influence of cystoid macular edema.
In retinitis pigmentosa patients the effect of cystoid macular edema on colour vision was studied. The occurrence of cystoid macular edema decreases with increasing colour vision defect. The mutual proportion of the main types of colour vision defects remains stable until visual acuity has dropped to 0.5; at lower VA levels the number of red-green defects increases. Neither the finding of a blue-yellow colour vision defect in FM100 Hue testing nor the appearance of anomaloscopic pseudoprotanomaly is influenced by cystoid macular edema. The authors conclude that cystoid macular edema in retinitis pigmentosa patients mainly affects visual acuity and not colour vision. They also noted a familial occurrence of cystoid macular edema.


[Information needs of patients with atopic eczema-a qualitative study].
Often patient information in atopic eczema (AE) does not meet the criteria of evidence-based patient information. What are the information needs of affected patients? The aim of the study was to analyze opinions and experiences of AE patients regarding their personal information needs. In all, 16 semi-structured interviews were conducted with patients with AE based on an interview guide. Subsequently the audio-taped interviews were transcribed and analyzed using deductive-inductive methods. Standards of qualitative research were ensured using the consolidated criteria for reporting qualitative research (COREQ). In all, 21 persons participated in the 16 interviews, including patients and relatives. Gender ratio was 2 : 1 (female/male); age varied between 19 and 75 years. The interviews revealed a gap in care for patient information about AE. Especially the lack of time in the physician-patients encounter was criticized. Many of the affected felt left alone and forced to take a more active role in the search for information and therapy itself. Depending on stage and duration of the disease, some persons had the impression that their search for information was too time-consuming in relation to the possible benefits. Patients perceived their doctor to be the most important contact person during the information seeking process. Within our study group, feeling a lack of a caring contact person as well as a lack of knowledge often led to not complying with a standardized, guideline-orientated therapy and of self-treatment. Filling this care gap seems to be an important approach to optimized patient care.


T2-weighted MR imaging of the liver: qualitative and quantitative comparison of SPACE MR imaging with turbo spin-echo MR imaging.
To qualitatively and quantitatively compare T2-weighted MR imaging of the liver using volumetric spin-echo with sampling perfection with application-optimized contrast using different flip angle evolutions (SPACE) with conventional turbo spin-echo (TSE) sequence for fat-suppressed T2-weighted MR imaging of the liver. Thirty-three patients with suspected focal liver lesions had SPACE MR imaging and conventional fat-suppressed TSE MR imaging. Images were analyzed quantitatively by measuring the lesion-to-liver contrast-to-noise ratio (CNR), and the signal-to-noise ratio (SNR) of main focal hepatic lesions, hepatic and splenic parenchyma and qualitatively by evaluating the presence of vascular, respiratory motion and cardiac artifacts. Wilcoxon signed rank test was used to search for differences between the two sequences. SPACE MR imaging showed significantly greater CNR for focal liver lesions (median=22.82) than TSE MR imaging (median=14.15) (P<.001). No differences were found for SNR of hepatic parenchyma (P=.097), main focal hepatic lesions (P=.35), and splenic parenchyma (P=.25). SPACE sequence showed less artifacts than TSE sequence (vascular, P<.001; respiratory motion, P<.001; cardiac, P<.001) but needed a longer acquisition time (228.4 vs. 162.1s; P<.001). SPACE MR imaging provides a significantly increased CNR for focal liver lesions and less artifacts by comparison with the conventional TSE sequence. These results should stimulate further clinical studies with a surgical standard of reference to compare the two techniques in terms of sensitivity for malignant lesions.


Hyperkinetic Choreiform Movements Secondary to Basal Ganglia Calcification and Underlying Developmental Venous Anomaly.
Chorea is irregular, involuntary movements that are associated with a variety of conditions and can encompass a wide differential. Unilateral hyperkinetic choreiform movements represent a rare subset characterized by the acute and sudden onset of progressive, uncontrollable body movements. We present a patient presenting with left-sided arm and leg arrhythmic movements caused by right-sided basal ganglia calcifications associated with an underlying developmental venous anomaly (DVA). To the author's knowledge, this is only the second reported case of such a presentation, and it should be on the differential in patients presenting with unilateral movement abnormalities.


Serum bilirubin concentrations and incident coronary heart disease risk among patients with type 2 diabetes: the Dongfeng-Tongji cohort.
Elevated serum bilirubin levels are associated with decreased coronary heart disease (CHD) risk in cross-sectional studies among diabetic patients, but prospective evidence is limited. We investigated the relationship of serum bilirubin levels with incident CHD risk among type 2 diabetes patients. In a prospective study of 2918 type 2 diabetes embedded in the Dongfeng-Tongji cohort, serum total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IBil) were measured at baseline. Cox proportional hazards models were used to examine the association between serum bilirubin levels and CHD risk. A total of 440 CHD cases were identified during 12,017 person-years of follow-up. Compared with extreme quartiles, the adjusted hazard ratio and 95% confidence interval of incident CHD were 0.74 (0.56-0.99) with P trend = 0.08 in IBil, while in TBil and DBil, the bilirubin-CHD associations were not significant. Moreover, serum TBil and IBil levels were interacted with drinking status on the risk of incident CHD (P interaction = 0.021 and 0.037, respectively), and the associations were evident in ever drinkers. In drinkers, when serum TBil or IBil concentrations increased 1 μmol/L, the CHD risk both decreased 6% (95% CIs 0.89-0.99 and 0.87-1.00, respectively). Serum IBil levels were marginally related to decreased incident CHD risk among type 2 diabetes. Drinking could potentially enhance the associations of serum TBil and DBil levels with incident CHD risk.


Predicting whole genome sequencing success for archived avian influenza virus (Orthomyxoviridae) samples using real-time and droplet PCRs.
Long-term viral archives are valuable sources of research data. Each archive can store hundreds of thousands of diverse sample types. In the current era of whole genome sequencing, archived samples become a rich source of evolutionary and epidemiological data that can span years, and even decades. However, the ability to obtain high quality viral whole genome sequences from samples of various types, age, and quality is inconsistent. A minimum quality threshold that helps predict the best success of obtaining high quality genomic sequences for both recent and archived samples is highly valuable. Real-time reverse transcription PCR (rrt-PCR) and droplet digital PCR (ddPCR) are useful tools to evaluate nucleic acid integrity. We hypothesized that diagnostic rrt-PCR and ddPCR data for avian influenza virus (AIV) can predict viral whole genome sequencing success. To test this hypothesis we used RNA extracted from cloacal and oropharyngeal swabs stored in the USDA-APHIS National Wildlife Disease Program Wildlife Tissue Archive. We determined that a specific rrt-PCR Cq value or ddPCR copies/μL resulted in recovery of complete sequences of all eight AIV gene segments. We used logistic regression to estimate probabilities of whole genome recovery at 0.95 (Cq = 15, copies/μL = 49,350), 0.75 (Cq = 24, copies/μL = 16,800), 0.50 (Cq = 29, copies/μL = <1), and 0.25 (Cq = 235, copies/μL = <1). We also identified values at which we predictably recovered HA and NA segments for diagnosing subtypes (Cq = 27.29; copies/μL = 757.50). This approach will allow researchers to assess the potential success of AIV whole genome recovery from diagnostic samples collected in routine AIV surveillance.


Development of a synthetic receptor protein for sensing inflammatory mediators interferon-γ and tumor necrosis factor-α.
Intestinal inflammation has been implicated in a number of diseases, including diabetes, Crohn's disease, and irritable bowel syndrome. Important components of inflammation are interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), which are elevated both on the luminal and submucosal sides of the intestinal epithelial barrier in several diseases. Here, we developed a novel Escherichia coli based detection system for IFN-γ and TNF-α comprised of a chimeric protein and a simple signal transduction construct, which could be deployed on the luminal side of the intestine. OmpA of E. coli was engineered to detect IFN-γ or TNF-α through the replacement of extracellular loops with peptide fragments from OprF of P. aeruginosa. OmpA/OprF chimeras were developed, capable of binding IFN-γ or TNF-α. The specific peptide fragments that bind IFN-γ were identified. IFN-γ or TNF-α binding the OmpA/OprF chimera induced the pspA promoter, driving β-galactosidase production. The OmpA/OprF chimera had a detection limit of 300 pM for IFN-γ and 150 pM for TNF-α. This work will further the development of bacteria based therapeutics for the treatment of inflammatory diseases of the gut.


mab-7 encodes a novel transmembrane protein that orchestrates sensory ray morphogenesis in C. elegans.
The tapered sensory rays of the male Caenorhabditis elegans are important for successful male/hermaphrodite copulation. A group of ram (ray morphology abnormal) genes encoding modifying enzymes and transmembrane protein have been reported as key regulators controlling ray morphogenesis. Here we report the characterization of another component essential for this morphogenetic process encoded by mab-7. This gene is active in the hypodermis, structural cells, the body seam and several head neurons. It encodes a novel protein with a hydrophobic region at the N-terminus, an EGF-like motif, an ShKT motif and a long C-terminal tail. All these domains are shown to be critical to MAB-7 activity except the EGF-like domain, which appears to be regulatory and dispensable. MAB-7 is shown to be a type II membrane protein, tethered on the cell surface by the N-terminal transmembrane domain with the remainder of the protein exposed to the extracellular matrix. Since ectopic mab-7 expression in any ray cell or even in touch neurons of non-ray lineage can rescue the mutant phenotype, mab-7 is probably acting non-autonomously. It may facilitate intercellular communication among ray cells to augment normal ray morphogenesis.


Effect of glucagon and insulin upon biliary lipid secretion.
The choleretic hormones, glucagon and insulin, were studied to determine whether they influence biliary lipid secretion in the dog. Glucagon was found to decrease biliary cholesterol and phospholipid secretion. These findings provide further support for a canalicular action of glucagon.


Utility of Göttingen minipigs for the prediction of human pharmacokinetic profiles after intravenous drug administration.
Göttingen minipigs are increasingly used to evaluate the pharmacokinetic (PK) profiles of drug candidates. However, their accuracy in predicting human PK parameters is unclear. In this study, we investigated the utility of Göttingen minipigs for predicting human PK profiles. We evaluated the PK parameters of 30 compounds with diverse metabolic pathways after intravenous administration in minipigs. Human total clearance (CLtotal) was corrected using the blood to plasma ratio, and the volume of distribution at steady state (Vd(ss)) was corrected with plasma unbound fraction (fup). CLtotal and Vd(ss) were predicted using single-species allometric scaling using data from minipigs and other reported animal models (monkeys, human liver chimeric mice, and rats). The predicted values were compared with actual values reported in humans. Göttingen minipig were superior to rats because of their better predictability of Vd(ss) and CLtotal, as represented by lower absolute average fold error values. However, their predictability for Vd(ss) was inferior to monkey and human liver chimeric mice. Prediction of CLtotal from blood-based minipig data showed excellent correlation with human data, and comparable predictability with monkey and human liver chimeric mice. Thus, Göttingen minipigs can be used as an optional model for preclinical pharmaceutical research for predicting human CLtotal.


Monoclonal antibody against the carboxy terminal peptide of pp60src of Rous sarcoma virus reacts with native pp60src.
A monoclonal mouse antibody has been prepared against a synthetic peptide corresponding to the six carboxy-terminal amino acids (C' peptide) of the src gene product pp60v -src of Rous sarcoma virus (RSV). The antibody was able to precipitate pp60v -src and to bind pp60v -src kinase activity in a competition test, indicating that this peptide can serve as an antibody-binding site (epitope). Furthermore, the finding that three out of 28 pp60src-specific tumor-bearing rabbit (TBR) sera contained antibody against the C' peptide argues for an in vivo role for the carboxy terminus of pp60src. C' peptide-specific IgG was purified from one TBR serum using affinity chromatography, and was shown to precipitate significant amounts of pp60src, and bind most of the pp60src kinase activity from SRA, PrA, and B77-C strains of avian sarcoma virus (ASV), but not endogenous pp60c -src, a cellular homologue to the viral pp60v -src. Similar results were obtained with IgG isolated from a C' peptide immune rabbit serum. None of the three C' peptide-specific IgGs could serve as a phosphate acceptor in an immune complex protein kinase reaction.


Challenging the assumptions in estimating protein fractional synthesis rate using a model of rodent protein turnover.
Published estimates of protein fractional synthetic rate vary widely (Johnson et al., 1999a). Contributing to the large standard deviation for FSR are physiological and methodological differences that do not account for changes in specific radioactivities of I, E, T, and P. Current methods for estimating FSR are based on four assumptions which may not be valid. The first assumption, that the free amino acid pool is homogenous and reflects the specific radioactivity of the true precursor pool (aminoacyl tRNA), can cause FSR estimates to increase by up to 8%/d. The second assumption, that recycling has an insignificant effect on FSR estimates, could result in decreases in estimates of FSR from 10 to 20%/d. The third assumption, that the protein pool is homogeneous and will not change over time, results in a 4-10%/d change using the flooding dose method. The fourth assumption, that growth will not affect estimated FSR over a short experimental time, is true if aminoacyl tRNA specific radioactivity is used to estimate FSR. Otherwise, estimates can vary 4-5%/d. Although specific radioactivity of aminoacyl tRNA is difficult to measure, the first and fourth assumptions are valid if aminoacyl tRNA specific radioactivity is used. Using a model of protein turnover, as described in this paper, to interpret specific radioactivity data allows the inclusion of all four assumptions and the potential to better quantify changes in FSR under different physiological conditions.


Reliability, discriminative accuracy, and an exploration of response shift as measured using the satisfaction and Recovery Index over 12 months from musculoskeletal trauma.
The Satisfaction and Recovery Index (SRI) is an importance-weighted health-related satisfaction tool intended to be a patient-centric means to capture both the process and state of recovery following musculoskeletal trauma. The purpose of this study was to explore measurement invariance, responsiveness, discriminative accuracy, and potential response shift identifiable within the SRI. Participants were 111 adults with acute musculoskeletal trauma. Data were collected at baseline, and again at 1, 2, 3, 6, and 12 months post-injury. Other tools used were the Brief Pain Inventory (BPI) and a Global Rating of Change scale. 1-month test-retest reliability (ICC2,1), responsiveness (standardized response mean in stable vs. changed participants), discriminative accuracy (area under the curve for differentiating between recovered and non-recovered), and response shift (change in mean importance scores over the 12-month period) were explored. All but the final analysis were compared against the BPI. Test-retest reliability was excellent across all metrics (ICC2,1 = 0.83 to 0.88). Responsiveness was greatest for the weighted SRI (SRM = 0.36) with MDC95 of 13.7%. All tools showed significant ability to discriminate between participants nominating recovery vs. non-recovery (AUC≥0.69) though the BPI subscales were significantly better than the SRI. Importance ratings showed small but significant change over time in 7 of the 9 SRI items. This study provides support for the SRI as a useful tool for evaluating recovery, though it seems more valuable for capturing the process rather than state of recovery. While response shift was small, there is enough reason to endorse retention of the importance ratings.


Acetic acid compared with i-scan imaging for detecting Barrett's esophagus: a randomized, comparative trial.
Traditional surveillance in patients with Barrett's esophagus (BE) has relied on random biopsies. Targeted biopsies that use advanced imaging modalities may significantly improve detection of specialized columnar epithelium (SCE). We compared the efficacy of targeted biopsies that used i-scan or acetic acid to random biopsies in the detection of SCE. Patients with visible columnar lined epithelium or known BE were randomized at a 1:1 ratio to undergo acetic acid application or i-scan with targeted biopsies. Targeted biopsies were performed based on surface architecture according to the Guelrud classification followed by 4-quadrant biopsies. A total of 95 patients were randomized. A total of 46 patients underwent acetic acid staining, and 49 underwent i-scan imaging. Random biopsies were performed in 86 patients. The primary outcome was the yield of SCE as confirmed by histologic assessment. The diagnostic yield for SCE was significantly higher with targeted biopsies than with random biopsies in both groups combined (63% vs 24%; P = .0001). The yield of targeted biopsies was significantly greater with both i-scan (66% vs 21%; P = .009) and acetic acid (57% vs 26%; P = .012) technologies and did not differ between these groups. The accuracy for predicting SCE was 96% (k = .92) for i-scan and 86% (k = .70) for acetic acid analysis. No dysplastic lesions were found. The i-scan or acetic acid-guided biopsies have a significantly higher diagnostic yield for identifying SCE, with significantly fewer biopsies, as compared with a protocol of random biopsies. Acetic acid and i-scan showed comparable results diagnosing SCE in our study. ( NCT01442506.).


Characterization of murine liver-derived inhibitory protein.
Murine liver-derived inhibitory protein (LIP) capable of inhibiting human lymphocyte proliferation was highly purified from liver extract. Its molecular weight determined by gel filtration and SDS-PAGE was 105,000 and 38,400 respectively. LIP moved electrophoretically at the gamma-globulin region. Its activity in inhibiting lymphocyte proliferation was temperature-stable up to 60 degrees C, and pH-stable between 4 and 11. It was not cytotoxic to lymphocytes as shown in 51Cr-release experiments. The purified LIP possessed arginase activity.


Predictors of Treatment Noncompletion in a Sample of Inpatient Sex Offenders With Serious Mental Illness.
Very little is known regarding noncompletion of sex offender treatment among sex offenders with serious psychiatric illness. The purpose of the study was to identify factors predictive of treatment noncompletion in a forensic psychiatric sample of 156 adult male sex offenders. All data were coded from archival client medical records. Variables of interest, including indicators of historical risk and clinical diagnoses made by hospital psychiatrists, were entered into both a linear regression equation with percentage of groups attended over two years as a continuous variable and a logistic regression equation for predicting more or less than 50% sex offender treatment group attendance. Significant predictors of treatment noncompletion included number of arrests, recent physical aggression, length of admission, and diagnoses of borderline personality disorder, psychosis, and intellectual impairments. The resulting predictors indicate a combination of relevant variables for psychiatric sex offenders, combining both criminal risk and clinical risk indicators. Suggested reasons for these findings and implications for predicting treatment noncompletion by psychiatric sex offenders are discussed.


Topographical mapping of epitopes on the glycoproteins of murine hepatitis virus-4 (strain JHM): correlation with biological activities.
Monoclonal hybridoma antibodies (MAb) of defined polypeptide specificity and biological activity were used in a competition binding assay to identify antibody binding sites (epitopes) on the glycoproteins of murine hepatitis virus-4 strain JHM (MHV-4). Individual MAb were labeled with horseradish peroxidase (HRP) and used as probes in a competition enzyme immunoassay (EIA). Four topographically distinct antigenic sites were detected on the E2 glycoprotein of MHV-4. Antibodies reacting with these four determinants provisionally designated A(E2), B(E2), C(E2), and D(E2) had corresponding biological activities (M. J. Buchmeier, H. A. Lewicki, P. J. Talbot, and R. L. Knobler (1984) Virology 132, 261-270). Antibodies to sites A(E2) and B(E2) mediated virus neutralization in vitro and passively protected mice against lethal virus challenge in vivo. Antibody to site C(E2) neutralized virus efficiently in vitro but did not alter disease in vivo, while antibody to site D(E2) neither neutralized nor protected. Two major nonoverlapping antigenic sites were defined on the E1 glycoprotein. Overlapping epitopes A(E1) and B(E1) constituted one site and epitope C(E1) the other.


Job design and staff satisfaction in human service settings.
It was hypothesized that job design is systematically related to employee satisfaction. The job design variables included were: variety, task-identity, feedback, autonomy participation, learning, and information. Subjects were 137 professional and nonprofessional employees of 22 agencies providing services to children. Agencies included mental health facilities, visiting nurse associations, residential care settings, and foster placement and adoption agencies. The hypothesis was supported. The correlations between specific jog design variables and work satisfaction were examined.


ARK5 is transcriptionally regulated by the Large-MAF family and mediates IGF-1-induced cell invasion in multiple myeloma: ARK5 as a new molecular determinant of malignant multiple myeloma.
ARK5, AMP-activated protein kinase (AMPK)-related protein kinase mediating Akt signals, is closely involved in tumor progression, and its stage-associated expression was observed in colorectal cancer. In this study, we found ARK5 expression in multiple myeloma cell lines expressing c-MAF and MAFB. In addition, gene expression profiling of 351 clinical specimens revealed ARK5 expression in primary myelomas expressing c-MAF and MAFB, suggesting that ARK5 may be a transcriptional target of the Large-MAF family. Sequence analysis of the ARK5 gene promoter revealed that it contains two putative MAF-recognition element (MARE) sequences. In support of this hypothesis, ARK5 was induced when an MAFB or c-MAF expression vector was introduced into non-ARK5-expressing colon cancer cells. Furthermore, ARK5 promoter activity was dramatically decreased by mutation or deletion of MARE sequences. Chromatin immunoprecipitation assays revealed an interaction between the Large-MAF family proteins and MARE sequences in the ARK5 promoter. Moreover, in ARK5 mRNA-expressing multiple myeloma lines, but not in ARK5-negative lines, insulin-like growth factor (IGF)-1 increased invasion activity. IGF-1-induced invasion was reproduced when ARK5 was overexpressed in Burkitt's lymphoma and plasmacytoma lines. Based on results, we conclude that ARK5 is a transcriptional target of the Large-MAF family through MARE sequence and that ARK5 may in part mediate the aggressive phenotype associated with c-MAF- and MAFB-expressing myelomas.


Dialogs in the assessment of neonatal cholestatic liver disease.
Neonatal cholestatic liver disease is rarely encountered by pathologists outside of specialized pediatric centers and navigating the long list of potential diseases can be daunting. However, the differential diagnosis can be rapidly narrowed through open conversations between the pathologist and pediatric gastroenterologist. The dialog should ideally begin before obtaining the liver biopsy and continue through the rendering of the final pathologic diagnosis. Such dialogs are necessary to first ensure the proper handling of the precious sample and then to allow for synthesis of the clinical, laboratory, imaging, and genetic data in the context of the histologic features seen in the liver biopsy. In this review, we aim to provide a broad template on which such dialogs may be based and pitfalls that may be encountered on both the clinical and pathologic sides. This review will focus on non-biliary atresia etiologies of neonatal cholestasis, including select infectious, genetic, and metabolic entities.