PrP gene polymorphism in sheep breeds in Slovakia and susceptibility to scrapie.
We analyzed the prion protein (PrP) genotype based on the codons 136, 154 and 171 and assigned to five risk groups (R1-R5) in healthy and scrapie-affected sheep in Slovakia. In healthy (asymptomatic) population, 119 Merino, 106 Improved Valachian, 117 Tsigai, and 48 Suffolk breeds were tested. Among the asymptomatic sheep, the low-risk genotypes R1 and R2 were most abundant in Suffolk (94%) and Merino (84%) breeds, followed by Tsigai (58%) and Improved Valachian (40%) breeds. The medium-risk group R3 was most frequent in Improved Valachian (31%) breed, followed by Tsigai (21%), Merino (10%), and Suffolk (6%) breeds. The occurrence of high-risk groups R4 and R5 was none in Suffolk breed, followed by Merino (6%), Tsigai (21%), and Improved Valachian (30%) breeds. Since 2003, altogether 48 cases of scrapie have been confirmed in Tsigai (38), Merino (4), Improved Valachian (2), Improved Valachian x Tsigai (3), and Suffolk (1) breeds. Among sheep with scrapie, Merino breed belonged to the medium-risk group R3. The majority of scrapie-affected Tsigai sheep were classified into high-risk R5 (50%) and medium-risk R3 (42%) groups. We showed an association of scrapie with medium- and high-risk groups of PrP genotype in Slovakia. In particular, the glutamine at position 171 appears to be of major importance for the susceptibility to scrapie.


Profile of 26 HIV Seropositive individuals with Cerebral Venous Thrombosis.
HIV infection has been found to be prothrombotic condition. However, venous thromboembolism associated with HIV is restricted to peripheral vasculature with few reports of cerebral venous thrombosis (CVT). To examine the clinical manifestations of CVT among HIV seropositive individuals and explore the possible etiological factors. It is a prospective study of 26 (M:F-18:8) patients of CVT associated with HIV seropositive status. Their age and duration of illness was 33.8±6.8years and 11.3±8.5days respectively. Headache and vomiting was the most common symptom followed by seizures. Drowsiness with GCS (Glasgow coma score) ranging from 9-14 was present in two-thirds of the patients. Serum homocysteine was elevated in 70% of patients. Vitamin B12 was low in 12.5% and insufficient levels in 25%. 88.5% of the patients recovered completely to GCS 15/15 in 2-7days during follow up; 11.5% patients expired during the acute state. This study represents the largest series of CVT in HIV seropositive individuals. There is increased risk of thrombosis due to elevated homocysteine and low Vitamin B12. They have better sensorium inspite of extensive radiological involvement.


Liposomal amphotericin B. Therapeutic use in the management of fungal infections and visceral leishmaniasis.
Incorporation of amphotericin B into small unilamellar liposomes (AmBisome) alters the pharmacokinetic properties of the drug, but allows it to retain significant in vitro and in vivo activity against fungal species, including Candida, Aspergillus and Cryptococcus, and parasites of the genus Leishmania. Used as prophylaxis against fungal infections in immunocompromised patients, liposomal amphotericin B appeared to reduce the incidence of both fungal colonisation and proven fungal infections, but did not affect overall survival. Empirical therapy with liposomal amphotericin B in immunocompromised adults or children with suspected fungal infections was at least as effective as therapy with conventional amphotericin B. In the largest noncomparative studies, liposomal amphotericin B produced mycological eradication in 40 and 83% of patients with proven Candida infections and 41 and 60% with proven Aspergillus infections; however, these studies included relatively few patients. Mycological eradication rates of 67 to 85% in patients with cryptococcal meningitis have been reported. Liposomal amphotericin B is an effective treatment for visceral leishmaniasis in immunocompetent adults and children, including those with severe or drug-resistant disease. The drug also produces good response rates in immunocompromised patients; however, relapse rates in these patients are high. Liposomal amphotericin B is generally well tolerated. Few patients require discontinuation or dose reduction of the drug because of adverse events. The most frequently reported adverse events are hypokalaemia, nephrotoxicity and infusion-related reactions; however, these occur significantly less often after liposomal amphotericin B than after the conventional formulation of the drug. The acquisition cost of liposomal amphotericin B is higher than that of conventional amphotericin B. Cost-effectiveness analysis did not clearly show an economic benefit for empirical liposomal amphotericin B antifungal therapy in adults; however, one model suggested that initial empirical therapy with the liposomal formulation in children may cost less per cure than initial therapy with the conventional formulation. Liposomal amphotericin B appears to be an effective alternative to conventional amphotericin B in the management of immunocompromised patients with proven or suspected fungal infections. Use of the drug is facilitated by its greatly improved tolerability profile compared with conventional amphotericin B. Because of this, liposomal amphotericin should be preferred to conventional amphotericin B in the management of suspected or proven fungal infections in immunocompromised patients with pre-existing renal dysfunction, amphotericin B-induced toxicity or failure to respond to conventional amphotericin B. Liposomal amphotericin B may also be considered for first- or second-line treatment of immunocompetent patients with visceral leishmaniasis.


Hibiscus rosa sinensis mediate anxiolytic effect via modulation of ionotropic GABA-A receptors: possible mechanism of action.
The current study was designed with the aim to investigate anti-anxiety potential of Hibiscus rosa sinensis roots and its possible mechanism of action. For this purpose hole board test, elevated plus maze test and light/dark exploration test were employed. The ethanol extract of plant was administered orally at two different doses i.e. 100 and 500 mg/kg for consecutive 14 days. The results of present investigation indicate that plant extract significantly (p < 0.05) increased the number of head dips and rearings as compared to control on respective days of observation. The extract increased the time of permanence in open arms and the number of head dips in elevated plus maze. In light/dark test, our study indicate that Hibiscus rosa sinensis significantly (p < 0.05) increased the time spent in light compartment and number of entries as compared to control. In addition the anxiolytic effects of HRS at highest tested dose were blocked by flumazenil, a GABA-A receptor antagonist that indicate that Hibiscus rosa sinensis potentiated the GABAergic actions. The results propose that the ethanol extract of Hibiscus rosa sinensis has prospective anxiolytic effect in mice via inhibition of ionotropic GABA receptors, using different behavioral paradigms.


Sketches in cyberspace: using student drawings of elders in an online social gerontology course.
Much of the literature on teaching gerontology derives from experiences in face-to-face settings. There is limited discussion of either the applicability of teaching techniques drawn from the traditional setting to the online environment or the development of novel strategies to engage distance students of aging. We developed and assessed an exercise designed to stimulate an online, asynchronous discussion of ageism in a Web-based social gerontology course. The exercise required students to analyze patterns found in sketches of elders drawn by themselves and their peers. The activity, which was favorably evaluated by our students, provided a springboard for discussion of the origins and consequences of ageism, as well as issues at the intersection of gender and age inequality.


Emerging fractal properties in gorgonian growth forms (Cnidaria: Octocorallia).
Gorgonian growth has been hitherto studied mostly by investigating the influence of different environmental conditions on shape and orientation. We have made an attempt at analyzing the intrinsic growth properties of these organisms, by using a method capable of pointing out a fractal arrangement. Colony outlines of the gorgonian species Eunicella singularis, Eunicella cavolinii, Paramuricea clavata, and Lophogorgia ceratophyta have been digitized and their length measured by traveling along them with a series of logarithmically increasing steps. When this procedure is used on fractal lines, logarithmic plots of estimated length vs. step show linear trends, whose slope yields the fractal dimension. In gorgonian outlines, due to their limited multi-scale organization, we have found curved trends typical of non-fractal lines. However, non-linear regression analysis has shown that the degree of bending is variable from curve to curve, with differences among species. also, in P. clavata and L. ceratophyta there is a positive correlation between the degree of development and the tendency to assume a fractal geometry. This suggests that gorgonian growth mechanisms retain a self-similar design, which becomes evident only in species combining a large size with a high branch density. Based on these data, possibilities of modeling biological patterns through fractal growth models are questioned.


Moisture Tolerant Pit and Fissure Sealant: A Literature Review.
Even in the 21st century, dental caries are considered a global burden, severely upsetting the health and quality of life of those affected. Apart from the fluoride use and regular oral hygiene, one of the most important prophylactic approaches against caries occurrence is the sealing of pits and fissures. Pit and fissure sealants are a core part of the preventive program in pediatric dentistry and should be considered as a key component of minimally invasive dentistry due to their broad patient benefit. The primary sealant efficacy measure is retention. If the sealant remains bonded to the tooth and offers a good seal, then it is right to expect the occurrence of caries to be diminished. Traditional pit and fissure sealants are hydrophobic. These materials are based on bisphenol A-glycidyl methacrylate (bis-GMA) and other monomers requiring a dry field which is hard to achieve in an oral environment, especially for children. This review highlights the literature on the effectiveness of moisture tolerant pit and fissure sealant, which are the hydrophilic pit and fissure sealant, and a general overview of the pit and fissure sealant materials used for sealing occlusal surfaces, its classification as well as indications and possible side effects. How to cite this article: Priscilla S, GS P, Mohandoss S. Moisture Tolerant Pit and Fissure Sealant: A Literature Review. Int J Clin Pediatr Dent 2022;15(2):233-239.


Utility of a standardized nursing terminology to evaluate dosage and tailoring of an HIV/AIDS adherence intervention.
To illustrate the utility of a standardized nursing terminology to calculate the dosage of the Client Adherence Profiling-Intervention Tailoring (CAP-IT) and to determine the extent to which a tailored intervention was delivered to 117 persons with HIV/AIDS who participated in the experimental arm of a randomized controlled trial (RCT). The intervention nurse assigned nursing diagnoses from the Home Health Care Classification (HHCC) based upon CAP scores. During the IT phase of CAP-IT, the nurse delivered and documented a tailored set of nursing interventions associated with the CAP and assigned nursing diagnoses. Hierarchical linear regression was used to evaluate the extent to which the number of interventions and intervention times were tailored to client needs. Linear regression models that included CAP scores and nursing diagnoses as predictor variables explained 53.2% of the variance in total number of interventions and 58.9% of the variance in intervention time. The use of the standardized nursing terminology enabled calculation of the intervention dose and documentation that a tailored intervention was delivered.


Interplay of anisotropy in shape and interactions in charged platelet suspensions.
Motivated by the intriguing phase behavior of charged colloidal platelets, we investigate the structure and dynamics of charged repulsive disks by means of Monte Carlo simulations. The electrostatic interactions are taken into account through an effective two-body potential, obtained within the nonlinear Poisson-Boltzmann formalism, which has the form of anisotropic screened Coulomb potential. Recently, we showed that the original intrinsic anisotropy of the electrostatic potential in competition with excluded volume effects leads to a rich phase behavior that not only includes various liquid-crystalline phases but also predicts the existence of novel structures composed of alternating nematic-antinematic sheets. Here, we examine the structural and dynamical signatures of each of the observed structures for both translational and rotational degrees of freedom. Finally, we discuss the influence of effective charge value and our results in relation to experimental findings on charged platelet suspensions.


Expression of the Ly6/uPAR-domain proteins C4.4A and Haldisin in non-invasive and invasive skin lesions.
C4.4A and Haldisin belong to the Ly6/uPAR/α-neurotoxin protein domain family. They exhibit highly regulated expression profiles in normal epidermis, where they are confined to early (C4.4A) and late (Haldisin) squamous differentiation. We have now explored if dysregulated expressions occur in non-invasive and invasive skin lesions. In non-invasive lesions, their expression signatures were largely maintained as defined by that of normal epidermis. The scenario was, however, markedly different in the progression towards invasive squamous cell carcinomas. In its non-invasive stage (carcinoma in situ), a pronounced attenuation of C4.4A expression was observed, but upon transition to malignant invasive squamous cell carcinomas, the invasive fronts regained high expression of C4.4A. A similar progression was observed for the early stages of benign infiltrating keratoacanthomas. Interestingly, this transition was accompanied by a shift in the predominant association of C4.4A expression with CK1/10 in the normal epidermis to CK5/14 in the invasive lesions. In contrast, Haldisin expression maintained its confinement to the most-differentiated cells and was hardly expressed in the invasive lesions. Because this altered expression of C4.4A was seen in the invasive front of benign (keratoacanthomas) and malignant (squamous cell carcinomas) neoplasms, we propose that this transition of expression is primarily related to the invasive process.


New 23, 27-dihydroxy-oleanane-type triterpenoid saponins from Anemone Raddeana Regel.
Two new 23, 27-dihydroxy-oleanane-type triterpenoid saponins named Raddeanoside Rf and Raddeanoside Rg (1 and 2), along with thirteen known triterpenoid saponins (3-15) were isolated from the rhizome of Anemone raddeana Regel. Their structures were determined by chemical and spectral analysis, including 1 D, 2 D NMR data and HRESIMS. The type of aglycone 23, 27-dihydroxy oleanolic acid is extremely rare in natural products. In addition, the anti-cancer activity for all the compounds were evaluated. Compounds 9 and 10 exhibited significant cytotoxicity with IC50 values of 4.47 and 8.97 μM against human pancreatic cancer lines (PANC-1), while compound 6 with IC50 value of 8.19 μM against human lung lines (A549). The possible structure-activity relationships of these triterpenoid saponins were also tentatively discussed.


Mental health services and R&D in South Korea.
World Health Organization has asserted that mental illness is the greatest overriding burden of disease in the majority of developed countries, and that the socioeconomic burden of mental disease will exceed that of cancer and cardiovascular disorders in the future. The life-time prevalence rate for mental disorders in Korea is reported at 27.6 %, which means three out of 10 adults experience mental disorders more than once throughout their lifetime. Korea's suicide rate has remained the highest among Organization for Economic Cooperation and Development (OECD) nations for 10 consecutive years, with 29.1 people out of every 100,000 having committed suicide. Nevertheless, a comprehensive study on the mental health services and the Research and Development (R&D) status in Korea is hard to find. Against this backdrop, this paper examines the mental health services and the R&D status in Korea, and examines their shortcomings and future direction. The paper discusses the mental health service system, budget and human resources, followed by the mental health R&D system and budget. And, by a comparison with other OECD countries, the areas for improvement are discussed and based on that, a future direction is suggested. This paper proposes three measures to realize mid and long-term mental health promotion services and to realize improvements in mental health R&D at the national level: first, establish a national mental health system; second, forecast demand for mental health; and third, secure and develop mental health professionals.


A Dataset and a Technique for Generalized Nuclear Segmentation for Computational Pathology.
Nuclear segmentation in digital microscopic tissue images can enable extraction of high-quality features for nuclear morphometrics and other analysis in computational pathology. Conventional image processing techniques, such as Otsu thresholding and watershed segmentation, do not work effectively on challenging cases, such as chromatin-sparse and crowded nuclei. In contrast, machine learning-based segmentation can generalize across various nuclear appearances. However, training machine learning algorithms requires data sets of images, in which a vast number of nuclei have been annotated. Publicly accessible and annotated data sets, along with widely agreed upon metrics to compare techniques, have catalyzed tremendous innovation and progress on other image classification problems, particularly in object recognition. Inspired by their success, we introduce a large publicly accessible data set of hematoxylin and eosin (H&E)-stained tissue images with more than 21000 painstakingly annotated nuclear boundaries, whose quality was validated by a medical doctor. Because our data set is taken from multiple hospitals and includes a diversity of nuclear appearances from several patients, disease states, and organs, techniques trained on it are likely to generalize well and work right out-of-the-box on other H&E-stained images. We also propose a new metric to evaluate nuclear segmentation results that penalizes object- and pixel-level errors in a unified manner, unlike previous metrics that penalize only one type of error. We also propose a segmentation technique based on deep learning that lays a special emphasis on identifying the nuclear boundaries, including those between the touching or overlapping nuclei, and works well on a diverse set of test images.


[Klinefelter syndrome with hypogonadotropic hypogonadism and absence of Leydig cells].
Klinefelter's syndrome is characterized by hypergonadotropic hypogonadism, 47,XXY karyotype, gynecomastia, azoospermia and testicular atrophy with hyalinization of seminiferous tubules and hyperplasia of Leydig cells. Some cases of Klinefelter's syndrome with unexplainably low levels of gonadotropins have been reported in the literature. Two additional cases of Klinefelter's syndrome with hypogonadotropic hypogonadism and absence of Leydig cells are described.


TCN, an AKT inhibitor, exhibits potent antitumor activity and enhances radiosensitivity in hypoxic esophageal squamous cell carcinoma in vitro and in vivo.
The aim of the present study was to investigate the radiosensitization effect of triciribine (TCN) on human esophageal squamous cell carcinoma (ESCC) in normoxia or hypoxia and its mechanism. The cytotoxicity and radiosensitization mechanism of TCN were investigated by Cell Counting Kit 8, clonogenic assay, flow cytometry, western blotting (WB) and immunofluorescence staining of phospho-histone H2A.X, Ser139 (γ-H2AX) in ESCC in vitro, while the protein expression levels of AKT, phosphorylated (p)-AKT, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) were evaluated by WB in vivo. The cytotoxicity of TCN was dose dependent. Upon exposure to TCN, ESCC cells in hypoxia treated with 4-Gy radiotherapy exhibited an evidently higher apoptotic rate than cells subjected to other treatments. TCN could significantly inhibit the protein expression of p-AKT, HIF-1α and VEGF in vitro and in vivo. The present results suggested that TCN can effectively inhibit AKT, p-AKT, HIF-1α and VEGF, thus conferring radiosensitivity to ESCC in vitro and vivo. TCN is considered as an adjuvant in radiotherapy of ESCC in clinical application.


Enhanced activity of pyrimidine 5'-nucleotidase in rat red blood cells during erythropoiesis.
A nucleotidase that catalyzed selective hydrolysis of pyrimidine 5'-nucleotides was investigated in rat red blood cells (RBCs). The enzyme had similar catalytic properties to human pyrimidine 5'-nucleotidase I (P5N-I). The P5N-I deficiency was known to be closely correlated with the human inherited disease, non-spherocytic hemolytic anemia. Similar to the human P5N-I, the rat enzyme preferentially hydrolyzed 5'-(d)CMP and 5'-UMP but no reactivity was observed with any 3'-nucleotide. Molecular mass of the enzyme was estimated to be approximately 38 kDa by gel filtration and SDS-polyacrylamide gel electrophoresis. Another subclass of pyrimidine 5'-nucleotidase, P5N-II, was also present in rat RBCs. This P5N-II-like enzyme, which resembled a 5'(3')-nucleotidase, preferentially hydrolyzed both 5'- and 3'- of (d)TMP or (d)UMP, but no cytosine nucleotide was hydrolyzed by the enzyme. Results from the reactivity with the antibody against rat 5'(3')-nucleotidase and estimated subunit molecular mass of the enzymes, about 26 kDa, suggested that the P5N-II-like enzyme had a similar structure to the 5'(3')-nucleotidase. The P5N-I-like activity in rat RBCs increased 5 to 6-fold at 4 days after phenylhydrazine injection, and reached a maximum at 6 to 7 days. No change in the activity of P5N-II-like nucleotidase was observed during the experimental period. The increase in rat P5N-I activity coincided with maturation of the erythrocytes.


Incidence of megaloblastic anaemia and its correction in leishmaniasis--a prospective study at BPKIHS hospital, Nepal.
Fifty (50) cases of Leishmaniasis were included in a prospective study after making the diagnosis based on the demonstration of L D Bodies on bone marrow aspirate. Hemoglobin (Hb) and total leucocyte count (TLC) were less than 10 gm/dl and 4000 per/ml respectively in 22 out of 50 cases. Among 50 cases, 30 showed macrocytic red cell and hypersegmented neutrophils on peripheral blood smear as features of megaloblastic anemia. Out of 30 cases of leishmaniasis with megaloblastic anemia, 10 cases showed decreased reticulocyte count. Bone marrow aspiration cytology showed megaloblastic maturation in erythroid series and giant metamyelocytes in myeloid series in all 30 cases of leishmaniasis with megaloblastic changes. Bone marrow iron was also increased in these cases. However megakaryocyte was normal in all. Among 30 cases of leishmaniasis with megaloblastic changes, 15 cases were treated with sodium antimony gluconate (SAG) only and other 15 with SAG, folic acid and Vit. B12. Rest 20 cases of leishmaniasis without megaloblastic changes were also treated with SAG only. After treatment with SAG alone as well as with SAG, folic acid and vit. B12, hemoglobin and TLC improved in all 50 cases. Of 15 cases of leishmaniasis with megaloblastic changes, who were treated with SAG, folic acid and vit. B12, the reticulocyte count reached at peak on the 7th day and normalized at the end of 4th week. Red blood cells (RBC) also became normocytic normochromic and neutrophils became normal on peripheral blood smear. But no change was observed in reticulocyte count, RBC and white blood cell (WBC) morphology on peripheral blood smear in cases of leishmaniasis without megaloblastic changes and other 15 cases of leishmaniasis with megaloblastic changes, who received SAG only.


Synthesis and properties of greenish-blue-emitting iridium dendrimers with N-phenylcarbazole-based polyether dendrons by a post-dendronization route.
A series of solution processible greenish-blue-emitting Ir dendrimers with polyether dendrons that consist of N-phenylcarbazole (NPC) are developed via a convenient post-dendronization method. It involves two steps: (i) the successful preparation of a reactive Ir core, namely m-HO-dfppyIr, only when the hydroxyl group is located at the meta position relative to the N atom in the C^N ligand so as to eliminate the possible resonance structure between enol and keto; and (ii) the subsequent functionalization with NPC-based polyether dendrons to afford the first, second and third generation Ir dendrimers (Ir-G1B, Ir-G2B and Ir-G3B) with ease and high yields over 60%. All these dendritic complexes possess good thermal stability with decomposition temperatures higher than 380 °C and glass transition temperatures higher than 200 °C. In addition, with the growing generation number, the intermolecular interactions between emissive Ir cores are expected to be effectively inhibited to avoid the luminescence quenching, which is confirmed from the blue-shifted emission peak and the enhanced lifetime of Ir-G3B in the solid state. As a result, on going from Ir-G1B to Ir-G3B, the maximum luminous efficiency rises upward from 4.7 to 9.2 cd A(-1) for nondoped electrophosphorescent devices. Further optimization by doping them into a dendritic H2 host leads to the improved luminous efficiencies as high as 20.0-25.2 cd A(-1).


Gallium cluster "magic melters".
Calorimetry measurements (using a method based on multicollision induced dissociation) have been performed for unsupported gallium clusters, Gan+ (n = 30-50 and 55). Melting transitions have been identified from spikes in the heat capacities recorded as a function of temperature. There are enormous fluctuations in the melting temperatures and the heats of fusion with cluster size. Clusters with n = 31, 33, 37, and 45-47 are "magic melters" with particularly well-defined melting transitions. There is a strong correlation between the heats of fusion, entropies of fusion, and the stabilities of the clusters. However, these quantities are not strongly correlated with the melting temperatures.


Human Organ-on-a-Chip Microphysiological Systems to Model Musculoskeletal Pathologies and Accelerate Therapeutic Discovery.
Human Microphysiological Systems (hMPS), otherwise known as organ- and tissue-on-a-chip models, are an emerging technology with the potential to replace in vivo animal studies with in vitro models that emulate human physiology at basic levels. hMPS platforms are designed to overcome limitations of two-dimensional (2D) cell culture systems by mimicking 3D tissue organization and microenvironmental cues that are physiologically and clinically relevant. Unlike animal studies, hMPS models can be configured for high content or high throughput screening in preclinical drug development. Applications in modeling acute and chronic injuries in the musculoskeletal system are slowly developing. However, the complexity and load bearing nature of musculoskeletal tissues and joints present unique challenges related to our limited understanding of disease mechanisms and the lack of consensus biomarkers to guide biological therapy development. With emphasis on examples of modeling musculoskeletal tissues, joints on chips, and organoids, this review highlights current trends of microphysiological systems technology. The review surveys state-of-the-art design and fabrication considerations inspired by lessons from bioreactors and biological variables emphasizing the role of induced pluripotent stem cells and genetic engineering in creating isogenic, patient-specific multicellular hMPS. The major challenges in modeling musculoskeletal tissues using hMPS chips are identified, including incorporating biological barriers, simulating joint compartments and heterogenous tissue interfaces, simulating immune interactions and inflammatory factors, simulating effects of in vivo loading, recording nociceptors responses as surrogates for pain outcomes, modeling the dynamic injury and healing responses by monitoring secreted proteins in real time, and creating arrayed formats for robotic high throughput screens. Overcoming these barriers will revolutionize musculoskeletal research by enabling physiologically relevant, predictive models of human tissues and joint diseases to accelerate and de-risk therapeutic discovery and translation to the clinic.


Modeling airway resistance dynamics after tidal and deep inspirations.
Using the forced oscillation technique, we tracked airway resistance continuously during quiet breathing (QB) and deep inspiration (DI), thus observing fluctuations in resistance that may reflect mechanisms of airway stretch and renarrowing. After DI, however, the resistance may be depressed for a period not related to volume changes. We hypothesized that this gradual increase in resistance after DI-induced dilation was determined by a simple time constant. Furthermore, to the extent that this effect reflects dynamic characteristics of airway renarrowing, the resistance change after each tidal inspiration should also be constrained by this temporal limit. A model relating resistance fluctuations to the breathing pattern, including both instantaneous and delayed effects, was developed and applied to data from 14 nonasthmatic and 17 asthmatic subjects (forced expiratory volume in 1 s = 103 +/- 13 and 83 +/- 12%, respectively, means +/- SD) after methacholine challenge (dose 145 +/- 80 and 3.0 +/- 3.4 micromol, respectively) that resulted in respective forced expiratory volume in 1 s reductions of 16 +/- 7 and 24 +/- 6% from baseline. Resistance was measured continuously for 1 min of QB, a DI, followed by a further minute of QB. Resistance values at end expiration (Ree) and end inspiration were calculated. We found that the sequence of Ree after DI was best modeled by a power-law function of time rather than an exponential decay (r2 = 0.82 +/- 0.18 compared with 0.63 +/- 0.16; P < 0.01). Furthermore, the coefficient characterizing this "renarrowing function" was close to equal to the coefficient characterizing the equivalent function of resistance change between each resistance value at end inpiration and subsequent Ree during QB, particularly in the nonasthmatic subjects for whom the intraclass correlation was 0.66. This suggests that the same time-dependent factors determine renarrowing after both large and small breaths.


Breast cancer survivors of different sexual orientations: which factors explain survivors' quality of life and adjustment?
Little is known about differences by sexual orientation in explanatory factors of breast cancer survivors' quality of life, anxiety, and depression. Survivors were recruited from a cancer registry and additional survivors recruited through convenience methods. Data were collected via telephone survey from all 438 survivors, who were disease free and diagnosed with non-metastatic breast cancer an average of 5 years earlier. To explain quality of life, anxiety, and depression, we focused on sexual orientation as the primary independent factors, in addition, considering demographic, psychosocial, clinical, and functional factors as correlates. Sexual orientation had indirect associations with each of the outcomes, through disease-related and demographic factors as well as psychosocial and coping resources. The various explanatory models explain between 36% and 50% of the variance in outcomes and identified areas of strengths and vulnerabilities in sexual minority compared with heterosexual survivors. This study's findings of strengths among specific subgroups of sexual minority compared with heterosexual survivors require further explorations to identify the reasons for this finding. Most of the identified vulnerabilities among sexual minority compared with heterosexual survivors of breast cancer are amenable to change by interventions.


Single-Protein Tracking Reveals That NADPH Mediates the Insertion of Cytochrome P450 Reductase into a Biomimetic of the Endoplasmic Reticulum.
Cytochrome P450 reductase (CPR) is the redox partner for most human cytochrome P450 enzymes. It is also believed that CPR is an integral membrane protein exclusively. Herein, we report that, contrary to this belief, CPR can exist as a peripheral membrane protein in the absence of NADPH and will transition to an integral membrane protein in the presence of stoichiometric amounts of NADPH or greater. All experiments were performed in a solid-supported cushioned lipid bilayer that closely matched the chemical composition of the human endoplasmic reticulum and served as an ER biomimetic. The phase characteristics and fluidity of the ER biomimetic was characterized with fluorescence micrographs and temperature-dependent fluorescence recovery after photobleaching. The interactions of CPR with the ER biomimetic were directly observed by tracking single CPR molecules using time-lapse single-molecule fluorescence imaging and subsequent analysis of tracks. These studies revealed dramatic changes in diffusion coefficient and the degree of partitioning of CPR as a function of NADPH concentration.


Visual cortex entrains to sign language.
Despite immense variability across languages, people can learn to understand any human language, spoken or signed. What neural mechanisms allow people to comprehend language across sensory modalities? When people listen to speech, electrophysiological oscillations in auditory cortex entrain to slow ([Formula: see text]8 Hz) fluctuations in the acoustic envelope. Entrainment to the speech envelope may reflect mechanisms specialized for auditory perception. Alternatively, flexible entrainment may be a general-purpose cortical mechanism that optimizes sensitivity to rhythmic information regardless of modality. Here, we test these proposals by examining cortical coherence to visual information in sign language. First, we develop a metric to quantify visual change over time. We find quasiperiodic fluctuations in sign language, characterized by lower frequencies than fluctuations in speech. Next, we test for entrainment of neural oscillations to visual change in sign language, using electroencephalography (EEG) in fluent speakers of American Sign Language (ASL) as they watch videos in ASL. We find significant cortical entrainment to visual oscillations in sign language <5 Hz, peaking at [Formula: see text]1 Hz. Coherence to sign is strongest over occipital and parietal cortex, in contrast to speech, where coherence is strongest over the auditory cortex. Nonsigners also show coherence to sign language, but entrainment at frontal sites is reduced relative to fluent signers. These results demonstrate that flexible cortical entrainment to language does not depend on neural processes that are specific to auditory speech perception. Low-frequency oscillatory entrainment may reflect a general cortical mechanism that maximizes sensitivity to informational peaks in time-varying signals.


Complete Genome Sequence of Brucella abortus Phage EF4, Determined Using Long-Read Sequencing.
Brucellaphage EF4 was isolated from elk feces. The 38,321-bp double-stranded DNA genome is predicted to contain 72 coding regions, 38 of which have been assigned predicted functions. This phage displays nucleotide similarity to other brucellaphages of the genus Perisivirus.


Behavioral contrast and relative reinforcement frequency in two multiple schedules.
After preliminary variable-interval training, one group of pigeons was trained on a series of multiple variable-interval low-rate reinforcement schedules, while another group was trained on a series of multiple variable-interval fixed-ratio reinforcement schedules. Contrast effects were observed as variable-interval baseline rate changed in a direction away from the change in reinforcement frequency in the other component. The effects of the variable-interval component on performance in the low-rate and fixed-ratio reinforcement components in the multiple schedules were assessed by comparing the birds' performances on each of these schedules alone. Fixed-ratio reinforcement schedules showed a susceptibility to contrast effects, low-rate reinforcement schedules did not. The rate of reinforcement in fixed-ratio schedules at which no interaction occurred in the multiple schedules was higher than that in variable-interval 1-min schedules, suggesting that pigeons may prefer time-based, rather than response-based, reinforcement.


[A Case of Stage IV Breast Cancer with Long-Term Survival by Chemotherapy Developing Pulmonary Tumor Thrombotic Microangiopathy during the Treatment Course].
Pulmonary tumor thrombotic microangiopathy(PTTM)caused by pulmonary artery microscopic tumor emboli and fibrocellular and/or fibromuscular proliferation leads to progressive pulmonary hypertension and respiratory failure.The prognosis is extremely poor and most patients die shortly after onset.We report a patient with Stage IV breast cancer and long-term survival who developed PTTM during chemotherapy treatment.A 63-year-old woman with multiple metastases in her cerebellum, bone, lung, and lymph node after left breast conserving surgery started to experience dyspnea and malaise 7 years after the surgery.Two months later, she was urgently admitted to hospital because of respiratory failure and was diagnosed with pulmonary hypertension.However, pulmonary thrombosis and tumor thrombus were not observed.We clinically diagnosed her with PTTM and administered chemotherapy in addition to treatment for pulmonary hypertension.Her medical condition improved gradually and she survived for the subsequent 2 years.When observing progressive hypoxia and pulmonary hypertension without obvious pulmonary embolism findings on imaging, PTTM should be considered.Early diagnosis and immediate induction of chemotherapy for primary disease can improve the survival of patients with PTTM.


DNA ploidy analysis and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma.
To investigate DNA ploidy and expression of MMP-9, TIMP-2, and E-cadherin in gastric carcinoma and to explore the mechanism of invasion and metastasis of gastric carcinoma. Immunohistochemical methods were used to detect the expressions of MMP-9, TIMP-2, and E-cadherin in 156 cases, including 99 cases of gastric carcinoma, 16 cases of adjacent noncancerous mucosa, 16 cases of distant metastases and 25 cases of metastatic lymph node (LN) from gastric carcinoma. Flow cytometry DNA ploidy and S-phase fraction (SPF) analysis were performed on 57 cases, including 47 cases of gastric cancer, 6 cases of adjacent noncancerous mucosa, and 4 cases of distant metastatic cancer. The expression of MMP-9 was significantly correlated with Lauren's classification, Borrmann's classification, LN metastasis, tumor metastasis, and TNM stage, as well as depth of invasion (all P<0.05). The positive rate was lower in noncarcinoma than in carcinoma (31.3% vs 66.7%, P<0.01). The expression of TIMP-2 was significantly correlated with Borrmann's classification, LN metastasis, and the depth of invasion (all P<0.05). The expression of E-cadherin was significantly correlated with differentiation, Lauren's classification, Borrmann's classification, and LN metastasis, as well as the depth of invasion (P<0.01 or P<0.05). E-cadherin was less expressed in carcinoma than in noncarcinoma (42.4% vs 87.5%, P<0.01). There was a positive correlation between MMP-9 and TIMP-2 and a negative correlation between MMP-9 and E-cadherin, but no correlation between TIMP-2 and E-cadherin. Also there was a positive correlation between DNA aneuploid rate and differentiation and LN metastasis. SPF that was higher than 15% was positively correlated with tumor size, differentiation and LN metastasis. And there was a significant difference between carcinoma and noncarcinoma in DNA aneuploid rate and SPF. With tumor progression and development of heterogeneity, the abnormal expressions of MMP-9, TIMP-2, and E-cadherin or DNA aneuploid rate or high SPF gradually increases, suggesting that they play a crucial role in gastric carcinoma progression.


Full-Genome Sequence of a Reassortant H1N2 Influenza A Virus Isolated from Pigs in Brazil.
In this study, the full-genome sequence of a reassortant H1N2 swine influenza virus is reported. The isolate has the hemagglutinin (HA) and neuraminidase (NA) genes from human lineage (H1-δ cluster and N2), and the internal genes (polymerase basic 1 [PB1], polymerase basic 2 [PB2], polymerase acidic [PA], nucleoprotein [NP], matrix [M], and nonstructural [NS]) are derived from human 2009 pandemic H1N1 (H1N1pdm09) virus.


Factors affecting the 27K DNA methylation pattern in asthmatic and healthy children from locations with various environments.
Gene expression levels are significantly regulated by DNA methylation. Differences in gene expression profiles in the populations from various locations with different environmental conditions were repeatedly observed. In this study we compare the methylation profiles in 200 blood samples of children (aged 7-15 years) with and without bronchial asthma from two regions in the Czech Republic with different levels of air pollution (a highly polluted Ostrava region and a control Prachatice region). Samples were collected in March 2010 when the mean concentrations of benzo[a]pyrene (B[a]P) measured by stationary monitoring were 10.1±2.4ng/m(3) in Ostrava Bartovice (5.6 times higher than in the control region). Significantly higher concentrations of other pollutants (benzene, NO2, respirable air particles and metals) were also found in Ostrava. We applied the Infinium Methylation Assay, using the Human Methylation 27K BeadChip with 27,578 CpG loci for identification of the DNA methylation pattern in studied groups. Results demonstrate a significant impact of different environmental conditions on the DNA methylation patterns of children from the two regions. We found 9916 CpG sites with significantly different methylation (beta value) between children from Ostrava vs. Prachatice from which 58 CpG sites had differences >10%. The methylation of all these 58 CpG sites was lower in children from polluted Ostrava, which indicates a higher gene expression in comparison with the control Prachatice region. We did not find a difference in DNA methylation patterns between children with and without bronchial asthma in individual locations, but patterns in both asthmatics and healthy children differed between Ostrava and Prachatice. Further, we show differences in DNA methylation pattern depending on gender and urinary cotinine levels. Other factors including length of gestation, birth weight and length of full breastfeeding are suggested as possible factors that can impact the DNA methylation pattern in future life.


Interactions between Host PPARs and Gut Microbiota in Health and Disease.
The human gastrointestinal tract is inhabited by many types of microbiota, including bacteria, viruses, and fungi. Dysregulations of their microenvironment are associated with various health problems, not only limited to gastrointestinal disorders, such as inflammatory bowel disease, but to impacts beyond the intestine. For example, intestinal microbiota can affect the liver in non-alcoholic fatty liver disease, visceral adipose tissue during adipogenesis, and the heart in atherosclerosis. The factors contributing to these pathogeneses involve the gut microbiota and the effector organs of the host, and everything in between. The nuclear receptor peroxisome proliferator-activated receptors (PPARs) are pivotal for the modulation of many of the pathogeneses mentioned above. It is, therefore, conceivable that, in the process of host-microbiota interactions, PPARs play important roles. In this review, we focus on the interactions between host PPARs in different organs and gut microbiota and their impacts on maintaining health and various diseases.


Current Status of Single-Site Robotic Cholecystectomy, its feasibility, economic and overall impact.
This paper reviews recent, though limited, articles on the topic of robotic single-site cholecystectomy (RSSC), a relatively new approach that is rapidly advancing in both research and clinical application. Laparoscopy has typically been the standard method of performing a cholecystectomy, but recent medical advances have led to usage of the da Vinci® Surgical System robot technology to assist in performing the procedure. Several studies have compared outcomes of the RSSC to single-port laparoscopic cholecystectomies and to the traditional multiport laparoscopic cholecystectomies. Single port advocates think it as a tool with better cosmetic results and questionable less post-operative pain; however, single port also limits the maneuverability of the instrument arms, making some tasks more difficult, bigger single incision, more chances of post operative hernia. Overall, the RSSC is considered as safe with no worse outcomes regarding pain, hospital stay length, operative time, and patient satisfaction when compared to other cholecystectomy methods. Future direction includes expanding use of the miniature instruments and further advanced tools to overcome manipulation and visualization limitations. Thus far, though, there may be enough evidence with these smaller studies to support lack of harm with more use of resources.


Stigma, social support, and treatment adherence among HIV-positive patients in Chiang Mai, Thailand.
Our study assessed the influence of HIV-related stigma on treatment adherence among people living with HIV in Chiang Mai, Thailand, and whether social support had a moderating effect on this relationship. We recruited 128 patients living with HIV from Sansai Hospital, a community hospital in Chiang Mai, Thailand, and collected data through structured interviews. All forms of HIV-related stigma considered in this study (personalized experience, disclosure, negative self-image, and public attitudes) were negatively correlated with adherence to anti-retroviral regimens. Multiple linear regression indicated that total HIV-related stigma was more predictive of treatment adherence than any individual stigma type, after adjusting for socio-demographic and health characteristics. Tests of interaction showed that social support did not appear to moderate the association between HIV stigma and treatment adherence. Our findings suggest that community and government efforts to improve public perceptions about people living with HIV might promote treatment adherence behaviors among HIV-positive patients.


Granulomatous slack skin. Histopathology diagnosis preceding clinical manifestations by 12 years.
Granulomatous slack skin is a very rare subtype of T-cell cutaneous lymphoma, characterized by the slow development of cutaneous sagging, especially on flexural areas. Its behavior is indolent and the treatment, in the majority of cases, disappointing. We report a 54-year-old black patient with granulomatous slack skin, who at the beginning of the investigation showed intense xeroderma and generalized lymph node enlargement. The diagnosis was established based on histopathologic findings long before the disease's characteristic clinical presentation appeared. During the twelve years of follow-up, the clinical manifestation evolved to marked skin looseness, most predominant in flexural regions, illustrating the clinical hallmark of granulomatous slack skin, long after first histological abnormalities were observed.


Effects on blood pressure decrease in response to PAF of Impatiens textori MIQ.
A 35% EtOH extract of flowers of Impatiens textori MIQ. showed an inhibitory effect on blood pressure decrease in response to platelet activating factor (PAF) measured with a blood pressure monitoring system. Bioassay-guided fractionation of the 35% EtOH extract (IT) led to isolation of the flavones apigenin (1) and luteolin (3), which significantly inhibited blood pressure decrease in response to PAF. Their compounds and apigenin 7-glucoside (2), chrysoeriol (4), quercetin (5), quercetin 3-glucoside (6), kaempferol (7), kaempferol 3-glucoside (8) and kaempferol 3-rhamnosyldiglucoside (9) were also isolated from the flowers of I. textori for the first time. This study revealed that the flowers of I. textori might be a possible anti-allergy agent.


Breastfeeding promotion plan in Madrid, Spain.
Promotion and protection of breastfeeding is a public health objective. In April 2009, health authorities in the Madrid region in central Spain signed a collaboration agreement with The United Nations Children's Fund and created a breastfeeding committee. To report the creation and implementation of a plan to promote and improve the quality of breastfeeding care in public hospitals in the region of Madrid, according to the Baby-Friendly Hospital Initiative (BFHI) standards. The action plan included institutional commitment; creation of a breastfeeding committee in each hospital; outcome analyses, staff training, creation of educational materials; and dissemination of activities. The plan was adopted by the 19 non-BFHI-designated public maternity units in the Madrid region. Each hospital completed a modified version of the World Health Organization self-assessment questionnaire in 2009 (pre-intervention) and again in 2011. Thirteen maternity units (68.4%) established a breastfeeding committee, and 32 months after implementation of the plan, the other 6 hospitals have created one. Nine training courses have been carried out to train professional experts on breastfeeding as trainers. The 271 trainers provided 18-hour breastfeeding courses for 1423 professionals. In 2009, there was only 1 BFHI-accredited hospital. Currently, 52.6% of the other 19 hospitals have some level of accreditation, and 2 are fully accredited. An intervention to improve the quality of breastfeeding care based on an organized regional approach to the BFHI was useful for BFHI implementation.


Preventive effect of 20(S)-ginsenoside Rg3 against lipopolysaccharide-induced hepatic and renal injury in rats.
The preventive effect of 20(S)-ginsenoside Rg(3) (20(S)-Rg(3)) on lipopolysaccharide (LPS)-induced oxidative tissue injury in rats was investigated in this study. The elevated serum nitrite/nitrate, glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and creatinine levels in LPS-treated control rats were significantly decreased following 15 consecutive days of 20(S)-Rg(3) administration. In addition, thiobarbituric acid-reactive substance levels in the serum, liver and kidney were dose-dependently lower in 20(S)-Rg(3)-treated groups than in the LPS-treated control group. The nuclear factor-kappaB (NF-kappaB), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1) protein expressions in the liver and kidney were significantly increased by LPS treatment. However, the 20(S)-Rg(3) administrations significantly decreased these protein expressions except for HO-1 in the liver. On the other hand, in the kidney, oral administration of 20(S)-Rg(3) showed a tendency to reduce NF-kappaB and iNOS protein expressions and also significantly reduced the elevated COX-2 and HO-1 protein expressions at a dose of 10 mg/kg body weight/day. All these results suggest the preventive effect of 20(S)-Rg(3) against LPS-induced acute oxidative damage in the liver and kidney and the preventive effect of 20(S)-Rg(3) administration against LPS toxicity was thought to be more predominant in the liver than kidney.


Modeling of the anticancer action for radical derivatives of nitroazoles: quantitative structure-activity relationship (QSAR) study.
A QSAR analysis of the anti-tumor, anti-metastasis and anti-colony formation (for metastatic colonies) activities of eighteen nitroazoles (including metronidazole and hypoxic radiosensitizers RP-170, KU-2285 and sanazole (drug AK-2123)) and their nitro and nitroso anion radical derivatives against melanoma B16 in mice has been performed. The QSAR models were built with the use of the frontal polygon method. This approach has features of different 3D QSAR methodologies and belongs to the group of "indirect" methods. The procedure allows to build robust models with high predictive ability even in series of diverse and conformationally flexible compounds. Key atomic characteristics accompany the geometrical requirements in the analysis of local 3D molecular similarity. By variation of weight coefficients for hydrophobicity, refraction increments, and partial charge it is possible to achieve better quality of QSAR and evaluate the importance of each characteristic for biological activity under consideration. It was found that hydrophobicity, molar refraction and charge characteristics of nitro anion radical derivatives are more significant for interaction with molecular targets than those of the parent compounds and of the nitroso anion radical derivatives. Size and hydrophobic properties of substituents in nitro anion radicals play significant role for ligand-target interaction in the processes of inhibition of metastatic spreading and growth of metastatic colonies by nitroazoles. A scheme of competitive interaction of parent nitroazoles and their anion radicals with a target in organism is suggested. It can be concluded that the step of one-electron reduction of nitroazoles can be important for anticancer activity of these drugs.


[3-dimensional imaging possibilities of thhe mid-face area using digital volume tomography based on a daver study of angle stable osteosynthesis].
Multidirectional angularly stable interlocking plate systems are now available for the surgical treatment of the midface. After first experiences in cases of mandibular fractures, application to the facial skeleton was investigated using a cadaver study. Furthermore, three-dimensional imaging by means of the digital volume tomograph NewTom DVT 9000 after reduction of orbitozygomatical fractures was performed and evaluated. After artificial osteotomy and reduction of both zygomatical complexes, osteosynthesis of the left side was performed with three 4-hole miniplates (2.0). On the right side, three angular stable 2-hole plates (2.3) were used. Thereafter, a three-dimensional data set was generated using the NewTom DVT 9000. After DICOM-import in eFilm reconstructions were evaluated by six examiners regarding defined criteria. After adaptation and fixation of the angular stable interlocking plate system without complications, manual checking revealed that the primary stability did not seem inferior to the other side. Defined criteria were sufficiently evaluable, even close to the osteosynthetic material, using reconstructions of the digital volume tomography data set. Surgical treatment of midfacial fractures using a multidirectional angularly stable interlocking plate system seems promising. The NewTom DVT 9000 proved to be suitable to visualize even fine osseous structures of the midface.


Phenytoin kinetics in children.
Previous studies have shown the importance of phenytoin kinetics in the management of adult patients with seizure disorders. The long half-life in adults makes single daily dosing realistic in terms of blood levels and anticonvulsant effectiveness. This report shows a wide range in both half-lives and volumes of distribution of phenytoin in 11 children (ages 6 months to 6 years) with seizure disorders. Ten of these patients have very short phenytoin half-lives (1.2 to 6.7 hours). The data strongly suggest that current recommendations for phenytoin dosage regimens in adults cannot necessarily be used in children. Blood levels must be followed closely in this age group to determine the required dosage and dose interval.


Cryogenic CO2 formation on oxidized gold clusters synthesized via reactive layer assisted deposition.
Gas-phase Au atoms deposited onto a multilayer film of molecular oxygen produce atomic oxygen bound to gold clusters. After removal of molecular O2, temperature programmed desorption and molecular beam techniques show that the atomic oxygen readily reacts with CO to produce CO2. At present, the structure and size distribution of these clusters are unknown. Nevertheless, CO2 forms on these clusters upon exposure to CO at temperatures as low as 35 K. Furthermore, above 120 K, the reaction goes to completion with initial reaction yields as high as 50%.


Effects of scutellarin on PKCgamma in PC12 cell injury induced by oxygen and glucose deprivation.
To evaluate the neuroprotective effect and mechanisms of scutellarin (Scu) against PC12 cell injury after oxygen and glucose deprivation followed by reperfusion (OGD-Rep). Undifferentiated rat pheochromocytoma PC12 cells, exposed to oxygen and glucose deprivation followed by reperfusion (OGD-Rep), used as an in vitro model of ischemia/reperfusion. Cell survival was evaluated by diphenyltetrazolium bromide (MTT) assay and the amount of LDH release was determined using assay kits. [Ca2+](i) was monitored using a fluorescent Ca2+-sensitive dye Fura-2 acetoxymethyl ester. Cell apoptosis was detected by a DNA ladder and by flow cytometric detection. The expression of protein kinase C (PKC)gamma was determined using both RT-PCR and Western blotting. The translocation of PKCgamma was assayed by subcellular fractionation and Western blotting. OGD-Rep injury significantly elevated the level of LDH release, [Ca2+](i), mRNA expression and the translocation of PKCgamma compared in the PC12 cells with those of the normal group. Scu (10-100 micromol/L) exerted a protective effect against OGD-Rep injury by reducing LDH release, [Ca2+](i), the percent of apoptosis, and the translocation of PKCgamma. Scu inhibits the increase of [Ca2+](i) and the activation of PKCgamma, exerting protective effects against PC12 cell injury induced by OGD-Rep.


18F-NaF PET/CT Findings in Fibrous Dysplasia.
A 43-year-old woman with breast cancer underwent Tc-hydroxymethylene diphosphonate bone scintigraphy for preoperative workup. An abnormal lesion with increased uptake was found in the right humeral shaft, and F-NaF bone PET/CT was performed for clarification. There was high uptake of F-NaF without cortical bone disruption in the right humeral shaft, corresponding to the site on bone scintigraphy. Upper arm MRI was performed subsequently, and metastasis was suggested as a differential diagnosis. However, this lesion was pathologically diagnosed as fibrous dysplasia after curettage surgery.


Floating-gate controlled programmable non-volatile black phosphorus PNP junction memory.
To meet the increasing requirements of minimizing circuits, the development of novel device architectures that use ultra-thin two-dimensional materials is encouraged. Here, we demonstrate a non-volatile black phosphorus (BP) PNP junction in a BP/h-BN/graphene heterostructure in which BP acts as a transport channel layer, hexagonal boron nitride (h-BN) serves as a tunnel barrier layer and graphene is the charge-trapping layer. The device architecture is designed such that only the middle part of the BP is aligned over the graphene flake, enabling the flexible tuning of the charge carriers in the BP over the graphene charge-trapping layer. Thus, the device exhibits the ability to work in two different operating modes (PNP and PP+P). Each operating mode can be retained well and demonstrates non-volatile behavior, and each can be programmed by using the control-gate.


Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application.
MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.


NGF regulates the expression of axonal LINGO-1 to inhibit oligodendrocyte differentiation and myelination.
Neurons and glia share a mutual dependence in establishing a functional relationship, and none is more evident than the process by which axons control myelination. Here, we identify LRR and Ig domain-containing, Nogo receptor-interacting protein (LINGO-1) as a potent axonal inhibitor of oligodendrocyte differentiation and myelination that is regulated by nerve growth factor and its cognate receptor TrkA in a dose-dependent manner. Whereas LINGO-1 expressed by oligodendrocyte progenitor cells was previously identified as an inhibitor of differentiation, we demonstrate that axonal expression of LINGO-1 inhibits differentiation with equal potency. Disruption of LINGO-1 on either cell type is sufficient to overcome the inhibitory action and promote differentiation and myelination, independent of axon diameter. Furthermore, these results were recapitulated in transgenic mice overexpressing the full length LINGO-1 under the neuronal promoter synapsin. Myelination was greatly inhibited in the presence of enforced axonal LINGO-1. The implications of these results relate specifically to the development of potential therapeutics targeting extrinsic growth factors that may regulate the axonal expression of modulators of oligodendrocyte development.


[Surgical diagnostic methods in the thoracic area].
Radiological changes in the lung, in the mediastinum and in the pleura should always be clarified. The thoracic surgery realizes methods, which have a minimal risk and a low rate of complications but have a high degree of efficacy. Those methods are biopsy of lymphatic nodes, mediastinoscopy and open chest pleuro-pulmonary biopsy. The methods are described and their indications and also their value is discussed in the scope of the diagnostic system of the lung clinic.


[Nephrogenic metaplasia of the bladder in renal transplant patients].
Nephrogenic metaplasia of the bladder is rare; less than one hundred cases have been reported. Four personal cases and 16 cases reported in the literature concerning renal transplant patients demonstrate that the frequency of this disease is much higher in this group than in the general population. The symptoms and signs, age of onset, macroscopic and microscopic appearance of the lesions correspond to the description in non-transplant patients, apart from the preferential site adjacent to the reimplanted ureter and the presence, in two cases, of cells with virus-like inclusions, one of which corresponded to CMV infection. The traumatic factor in these patients is not sufficient on its own to explain the relative frequency of this lesion in renal transplant patients. The role of immunosuppression, resulting in a reduction of "immunological surveillance", is possible; this metaplasia usually has a benign course, but this high risk population must be carefully monitored for the development of this lesion.


[The treatment of appendicular peritonitis complicated by septic shock in childhood].
The article presents an analysis of results of treatment of 39 children from 1 to 14 years of age with diagnosis of appendicular peritonitis complicated by septic shock. It was shown that complex pathogenetic treatment with controlled laparostomy, necessary compulsory or subsidiary artificial pulmonary ventilation before and after operative intervention, associated use of afferent methods allowed to decrease the number of lethal outcomes from 54.5 to 11.1%.


Temperature and salinity correction coefficients for light absorption by water in the visible to infrared spectral region.
The light absorption coefficient of water is dependent on temperature and concentration of ions, i.e. the salinity in seawater. Accurate knowledge of the water absorption coefficient, a, and/or its temperature and salinity correction coefficients, Ψ(T) and Ψ(S), respectively, is essential for a wide range of optical applications. Values are available from published data only at specific narrow wavelength ranges or at single wavelengths in the visible and infrared regions. Ψ(T) and Ψ(S) were therefore spectrophotometrically measured throughout the visible, near, and short wavelength infrared spectral region (400 to ~2700 nm). Additionally, they were derived from more precise measurements with a point-source integrating-cavity absorption meter (PSICAM) for 400 to 700 nm. When combined with earlier measurements from the literature in the range of 2600 - 14000 nm (wavenumber: 3800 - 700 cm(-1)), the coefficients are provided for 400 to 14000 nm (wavenumber: 25000 to 700 cm(-1)).


Bleomycin-induced pulmonary fibrosis mimicking recurrent metastatic disease in a patient with testicular carcinoma: case report of the CT scan appearance.
Pulmonary fibrosis is a well-recognized complication of bleomycin therapy. Detection of bleomycin-induced pulmonary fibrosis by computed axial tomographic scanning (CT) has not been reported. We report on a patient in whom the development of lesions on chest CT scan following cessation of chemotherapy (including bleomycin) was interpreted as representing recurrent metastatic disease. At bilateral thoracotomy, only pulmonary fibrosis was found. In this patient, the CT scan appearance of bleomycin-induced pulmonary fibrosis mimicked recurrent disease.


Post-traumatic refractory multiple canal benign paroxysmal positional vertigo: a case report.
Benign paroxysmal positional vertigo (BPPV) is the most prevalent form of peripheral vertigo and is seen in a significant number of patients who present at neurology and ear, nose, and throat clinics. Various maneuvers may be used to determine the affected canal based on observation of specific nystagmus signs, and may also be used for treatment. Multiple canal pathology can make diagnosis and treatment more difficult. Presently described is case of BPPV with multiple canal pathology and traumatic etiology that was resistant to treatment.


Secondary confounders of osteoporotic hip fractures in patients admitted to a geriatric acute care department.
With respect to the pathogenesis of osteoporosis, primary and secondary forms of the disease can be distinguished. It has been recognized that the incidence of primary and secondary osteoporosis differs in women and men. The aim of the present study was to assess the incidence and gender distribution of factors contributing to osteoporosis in older hip fracture patients. In this cross-sectional study 404 patients with hip fractures and controls referred to an acute geriatric care department over a period of 15 months were included. The medical history was recorded and blood samples were analyzed for routine laboratory parameters. A total of 249 patients with hip fractures and 155 matched controls were studied. The Tinetti test and the Barthel index were found to show highly significant differences in both groups mainly because of the postoperative state of patients with fractures. Vitamin D deficiency was found in 94.1% of male fracture patients and 94.6% of female fracture patients. On average 2.4 secondary contributors of osteoporosis were present in male fracture patients versus 2.9 in male controls and 2.3 in female fracture patients versus 2.3 in female controls. For most parameters no significant gender differences of possible secondary contributors to osteoporosis were found. Secondary osteoporosis was diagnosed in all male fracture patients and in 56.2% of all female fracture patients. Based on the findings of this study it is recommended that hip fracture patients should be assessed for secondary contributors of osteoporosis. Although the overall distribution of secondary contributors was similar in women and men, the prevalence of secondary osteoporosis was higher in men.


Combined Ultraviolet Ozone and Thermally Activated Formamidinium Iodide Solution to Fabricate Large Grain FAPbI2.6Br0.3Cl0.1 Films.
In this report, we report the fabrication of a large grain and high crystallinity perovskite film by combined ultraviolet-ozone (UVO) and thermal treatment of formamidinium iodide solution during the fabrication of formamidinium lead halide (FAPbI2.6Br0.3Cl0.1) films by a two-step deposition method. In this process, lead halide films were treated with UVO-treated FAI at different times. In addition, we have observed that hot-casting of UVO-assisted FAI nucleates the α-FAPbI3 phase in as-prepared films. Again, we observed that the annealed hot-cast UVO-assisted FAI increased the grain size and crystallinity in the films. It was observed that the perovskite film fabricated using 10 min UVO-treated FAI solution shows the highest power conversion efficiency (PCE) up to 17.74%. Furthermore, the perovskite film fabricated with the hot-cast at 120 °C with the 10 min UVO-treated FAI solution improved the PCE to 19.22%. This finding would help with fabrication of large grain, smooth, uniform, and pinhole perovskite films by combining UVO and thermally assisted FAI solution.


Amino acid alanine reactivity with the fingerprint reagent ninhydrin. A detailed ab initio computational study.
Ninhydrin is one of the most widely used reagents for chemical development of fingerprints on porous surfaces. The detection is based on the reaction of ninhydrin with a monoacidic component of the fingerprint to form an intensively colored compound named Ruhemann's Purple. A computational study of the mechanisms and reaction energetics of the formation of Ruhemann's Purple from ninhydrin and alanine is presented. Such a study is significant from a forensic science point of view because of the strong interest in the forensic chemistry and law enforcement communities in developing alternatives to the current generation of ninhydrin like chemicals for the detection and development of latent fingerprints. Information about the mechanism of reaction between ninhydrin and amino acids can ultimately help to design compounds with stronger chromo-fluorogenic properties in aid of detecting fingerprints at crime scenes. The three most accepted mechanisms of formation have been considered using ab initio quantum mechanical calculations. At relatively high temperature ( approximately 100 degrees C) all three mechanisms are energetically feasible. However since it is recommended that forensic analyses be performed at room temperature, a revised mechanism is proposed for the formation of Ruhemann's Purple under this condition.


Stimuli-Responsive Conductive Nanocomposite Hydrogels with High Stretchability, Self-Healing, Adhesiveness, and 3D Printability for Human Motion Sensing.
Self-healing, adhesive conductive hydrogels are of great significance in wearable electronic devices, flexible printable electronics, and tissue engineering scaffolds. However, designing self-healing hydrogels with multifunctional properties such as high conductivity, excellent mechanical property, and high sensitivity remains a challenge. In this work, the conductive self-healing nanocomposite hydrogels based on nanoclay (laponite), multiwalled carbon nanotubes (CNTs), and N-isopropyl acrylamide are presented. The presented nanocomposite hydrogels displayed good electrical conductivity, rapid self-healing and adhesive properties, flexible and stretchable mechanical properties, and high sensitivity to near-infrared light and temperature. These excellent properties of the hydrogels are demonstrated by the three-dimensional (3D) bulky pressure-dependent device, human activity monitoring device, and 3D printed gridding scaffolds. Good cytocompatibility of the conductive hydrogels was also evaluated with L929 fibroblast cells. These nanocomposite hydrogels have great potential for applications in stimuli-responsive electrical devices, wearable electronics, and so on.


Ocular Effects of Glycyrrhizin at Acidic and Neutral pH.
To test the effects of acidic vs. neutral pH glycyrrhizin (GLY) on the unwounded and wounded normal mouse cornea and after infection with Pseudomonas aeruginosa isolates KEI 1025 and multidrug-resistant MDR9. Acidic or neutral GLY vs. phosphate-buffered saline (PBS) was topically applied to normal or wounded corneas of C57BL/6 mice. In unwounded corneas, goblet cells and corneal nerves were stained and quantitated. After wounding, corneas were fluorescein stained and photographed using a slit lamp. Mice also were infected with KEI 1025 or MDR9 and the protective effects of GLY pH evaluated comparatively. In the unwounded cornea, application of acidic or neutral GLY vs. PBS reduced the number of bulbar conjunctival goblet cells but did not alter corneal nerve density. Similar application of GLY to scarified corneas delayed wound closure. After KEI 1025 infection, none of the GLY vs. PBS-treated corneas perforated; GLY treatment also decreased plate count (neutral pH more effective) and reduced MPO and several cytokines. Similarly, for MDR9, GLY at either pH was protective and also enhanced the effects of moxifloxacin to which MDR9 is resistant. Acidic or neutral pH GLY decreased goblet cell number but had no effect on nerve density. After corneal wounding, GLY at either pH (1) delayed wound closure and, (2) after infection, decreased keratitis when used alone or in combination with moxifloxacin. Neutral pH did not alter the therapeutic effect of GLY and would be preferred if used clinically.


Interaction between 14mer DNA oligonucleotide and cationic surfactants of various chain lengths.
In the recent genomic era, a novel gene silencing approach has been introduced based on the use of small synthetic oligonucleotides, such as antisense RNAs, siRNAs, to inhibit the expression of a specific target gene. Successful implementation of this methodology calls for the development of efficient systems to deliver small oligonucleotides into the cells using various natural and synthetic cationic agents. While extensive studies have focused on the interaction of various natural and synthetic cationic surfactants with long DNA, less attention has been paid to surfactant interaction with small oligonucleotides. In this study, the interaction between 14mer double stranded DNA and alkyltrimethylammonium bromides of C16 (cetyl, CTAB), C14 (tetradecyl, TTAB), and C12 (dodecyl, DTAB) chain lengths was investigated at different charge ratios by gel electrophoresis, ethidium bromide exclusion, circular dichroism, and UV melting. Our gel studies at 1 microM oligonucleotide concentration showed that CTAB, TTAB, and DTAB neutralize the oligonucleotides at a charge ratio (Z+/-) of 1, 14, and 50, respectively. At lower charge ratios, CTAB and TTAB interact with oligonucleotides, and the complexes show electrophoretic mobility shifts in the gel, while such mobility shifts were completely absent in the case of DTAB. UV melting experiments revealed that interaction with all three surfactants increased the thermostability of the oligonucleotide. The extent of thermal stabilization was highest in the case of CTAB, moderate in the case of TTAB, and extremely low in the case of DTAB. Oligonucleotides within fully neutralized complexes denatured at further higher temperatures, and again, stabilization was the highest in the case of CTAB followed by TTAB and DTAB, hence revealing that the oligonucleotides interacted more strongly with CTAB than with the other two surfactants. Ethidium bromide exclusion studies also supported our UV melting studies, confirming that CTAB binds most strongly to the oligonucleotide. CD titrations of oligonucleotides with increasing amounts of surfactants revealed common spectral patterns consisting of the progressive loss of CD signals for native helical DNA conformations. Overall, our results demonstrate that interaction between oligonucleotides and cationic surfactants, although qualitatively similar to long double stranded DNA, shows subtle differences that need to be understood to improve small oligonucleotide delivery into the cells by using common delivery agents that have been used to deliver long pieces of DNA.


Recent trends in liver transplantation for alcoholic liver disease in the United States.
To examine temporal changes in the indications for liver transplantation (LT) and characteristics of patients transplanted for alcoholic liver disease (ALD). We performed a retrospective cohort analysis of trends in the indication for LT using the United Network for Organ Sharing (UNOS) database between 2002 and 2015. Patients were grouped by etiology of the liver disease and characteristics were compared using χ2 and t-tests. Time series analysis was used identifying any year with a significant change in the number of transplants per year for ALD, and before and after eras were modeled using a general linear model. Subgroup analysis of recipients with ALD was performed by age group, gender, UNOS region and etiology (alcoholic cirrhosis, alcoholic hepatitis and hepatitis C - alcoholic cirrhosis dual listing). Of 74216 liver transplant recipients, ALD (n = 9400, 12.7%) was the third leading indication for transplant after hepatitis C and hepatocellular carcinoma. Transplants for ALD, increased from 12.8% (553) in 2002 to 16.5% (1020) in 2015. Time series analysis indicated a significant increase in the number of transplants per year for ALD in 2013 (P = 0.03). There were a stable number of transplants per year between 2002 and 2012 (linear coefficient 3, 95%CI: -4.6, 11.2) an increase of 177 per year between 2013 and 2015 (95%CI: 119, 234). This increase was significant for all age groups except those 71-83 years old, was observed for both genders, and was incompletely explained by a decrease in transplants for hepatitis C and ALD dual listing. All UNOS regions except region 9 saw an increase in the mean number of transplants per year when comparing eras, and this increase was significant in regions 2, 3, 4, 5, 6, 8, 10 and 11. There has been a dramatic increase in the number of transplants for ALD starting in 2013.


Advances in alfalfa mosaic virus-mediated expression of anthrax antigen in planta.
Plant viruses show great potential for production of pharmaceuticals in plants. Such viruses can harbor a small antigenic peptide(s) as a part of their coat proteins (CP) and elicit an antigen-specific immune response. Here, we report the high yield and consistency in production of recombinant alfalfa mosaic virus (AlMV) particles for specific presentation of the small loop 15 amino acid epitope from domain-4 of the Bacillus anthracis protective antigen (PA-D4s). The epitope was inserted immediately after the first 25 N-terminal amino acids of AlMV CP to retain genome activation and binding of CP to viral RNAs. Recombinant AlMV particles were efficiently produced in tobacco, easily purified for immunological analysis, and exhibited extended stability and systemic proliferation in planta. Intraperitional injections of mice with recombinant plant virus particles harboring the PA-D4s epitope elicited a distinct immune response. Western blotting and ELISA analysis showed that sera from immunized mice recognized both native PA antigen and the AlMV CP.


Essential oils: their antibacterial properties and potential applications in foods--a review.
In vitro studies have demonstrated antibacterial activity of essential oils (EOs) against Listeria monocytogenes, Salmonella typhimurium, Escherichia coli O157:H7, Shigella dysenteria, Bacillus cereus and Staphylococcus aureus at levels between 0.2 and 10 microl ml(-1). Gram-negative organisms are slightly less susceptible than gram-positive bacteria. A number of EO components has been identified as effective antibacterials, e.g. carvacrol, thymol, eugenol, perillaldehyde, cinnamaldehyde and cinnamic acid, having minimum inhibitory concentrations (MICs) of 0.05-5 microl ml(-1) in vitro. A higher concentration is needed to achieve the same effect in foods. Studies with fresh meat, meat products, fish, milk, dairy products, vegetables, fruit and cooked rice have shown that the concentration needed to achieve a significant antibacterial effect is around 0.5-20 microl g(-1) in foods and about 0.1-10 microl ml(-1) in solutions for washing fruit and vegetables. EOs comprise a large number of components and it is likely that their mode of action involves several targets in the bacterial cell. The hydrophobicity of EOs enables them to partition in the lipids of the cell membrane and mitochondria, rendering them permeable and leading to leakage of cell contents. Physical conditions that improve the action of EOs are low pH, low temperature and low oxygen levels. Synergism has been observed between carvacrol and its precursor p-cymene and between cinnamaldehyde and eugenol. Synergy between EO components and mild preservation methods has also been observed. Some EO components are legally registered flavourings in the EU and the USA. Undesirable organoleptic effects can be limited by careful selection of EOs according to the type of food.


Relocation is the key to successful correlative fluorescence and scanning electron microscopy.
In this chapter the authors report on an automated hardware and software solution enabling swift correlative sample array mapping of fluorescently stained molecules within cells and tissues across length scales. Samples are first observed utilizing wide-field optical and fluorescence microscopy, followed by scanning electron microscopy, using calibration points on a dedicated sample-relocation holder. We investigated HeLa cells in vitro, fluorescently labeled for monosialoganglioside one (GM-1), across both imaging platforms within tens of minutes of initial sample preparation. This resulted in a high-throughput and high spatially resolved correlative fluorescence and electron microscopy analysis and allowed us to collect complementary nanoscopic information on the molecular and structural composition of two differently distinct HeLa cell populations expressing different levels of GM-1. Furthermore, using the small zebrafish animal model Danio rerio, we showed the versatility and relocation accuracy of the sample-relocation holder to locate fluo-tagged macromolecular complexes within large volumes using long ribbons of serial tissue sections. The subsequent electron microscopy imaging of the tissue arrays of interest enabled the generation of correlated information on the fine distribution of albumin within hepatic and kidney tissue. Our approach underpins the merits that an automated sample-relocation holder solution brings in support of results-driven research, where relevant biological questions can be answered, and high-throughput data can be generated in a rigorous statistical manner.


Health literacy in the urgent care setting: What factors impact consumer comprehension of health information?
An increasing number of Americans are using urgent care (UC) clinics due to: improved health insurance coverage, the need to decrease cost, primary care offices with limited appointment availability, and a desire for convenient care. Patients are treated by providers they may not know for episodic illness or injuries while in pain or not feeling well. Treatment instructions and follow-up directions are provided quickly. To examine health literacy in the adult UC population and identify patient characteristics associated with health literacy risk. As part of a larger cross-sectional study, UC patients seen between October 2013 and January 2014 completed a demographic questionnaire and the Newest Vital Sign. Descriptive, nonparametric analyses, and a multinomial logistic regression were done to assess health literacy, associated and predictive factors. A total of 57.5% of 285 participants had adequate health literacy. The likelihood of limited health literacy was associated with increased age (p < .001), less education (p < .001), and lower income (p = .006). Limited health literacy is common in a suburban UC setting, increasing the risk that consumers may not understand vital health information. Clear provider communication and confirmation of comprehension of discharge instructions for self-management is essential to optimize outcomes for UC patients.


Applying a modified Donnan model to describe the surface complexation of chromate to iron oxyhydroxide agglomerates with heteromorphous pores.
In this study, a modified Donnan model (mDM) is incorporated into surface complexation model (SCM) to better understand the physicochemical processes for adsorption of hexavalent chromium, Cr(VI), on porous iron oxyhydroxide agglomerates (IOAs). The mDM includes a chemical potential term μatt to account for ionic transport and electrostatic interaction in micropores (dmi<2nm) which is usually neglected in typical Donnan model (tDM). To estimate the parameters of mDM in a simple and accurate way, a rigorous protocol was presented. First, the prepared IOAs was characterized with a heteromorphous pore structure (i.e., co-existing micropores and macropores, dma>2nm) demonstrating high Cr(VI) adsorption in a broad range of ionic strengths. The batch data was then fitted with Donnan model in PHREEQC to obtain Stern (ψS) and Donnan (ψD) potentials used for μatt calculation. The decreasing μatt values with ionic strength indicated obstructing effect of electrolyte ions on Cr(VI) uptake in micropores. Finally, the ionic activity coefficients and reaction constants were corrected using Pitzer model due to the high level electrolytes accumulated in the Donnan layer through osmotic and electrostatic attraction. Results of this study have captured the effects of inner structure of IOAs on Cr(VI) uptake and quantitatively discerned the contribution of micropores and macropores for adsorption reactions at different ionic strengths.


Disseminated Mycobacterium malmoense infection in a patient with chronic granulocytic leukaemia.
Mycobacterium malmoense is an atypical mycobacterium previously isolated from lymph nodes in children and from adults with pulmonary disease. Disseminated infection is extremely rare and bone marrow involvement has never previously been described. We report a patient with chronic granulocytic leukaemia and persistent fever with granuloma in the bone marrow due to disseminated M. malmoense infection. The patient initially received treatment with isoniazid, ethambutol and rifampicin with clearance of mycobacteria in the bone marrow and clinical improvement. Sensitivity in vitro was established for streptomycin, amikacin, ethambutol and rifabutin. The patient eventually expired as a result of progressive respiratory failure from other opportunistic infections. At autopsy staining of samples from lung parenchyma revealed fungal hyphi but staining for Pneumocystis carinii and myobacteria were negative.


Scintigraphic study of duodenogastric reflux. Value of a computerized image-subtraction method.
Duodenogastric reflux (DGR) could be implicated in several esophageal and gastric diseases. Establishing its pathophysiological role however is difficult because of the problems in the demonstration and quantification of DGR episodes. The aim of this study was to improve a scintigraphic method of detection and quantification of DGR episodes during the postprandial period in man. The study was carried out in 14 control subjects (7 males and 7 females, median age = 25 years, range: 22-35 years). As scintigraphic recording was continuous during 150 min, all DGR episodes were revealed. In order to improve visual detection of DGR episodes, images were treated by a computerized image subtraction method. The visual detection limit of DGR episodes determined by comparison to test images was 0.6 p. 100 of the dose injected intravenously or 17 microCi. A DGR episode was demonstrated in one of the 14 control subjects. The quantity of refluxed liquid was estimated, in this case, at 30 microCi, and the duration of the reflux greater than 2 min. Continuous scintigraphic recording in association with a computer based technique of image subtraction seems to improve scintigraphic performance in the study of DGR episodes under pathological conditions.


Selective vulnerability in Huntington's disease: preferential loss of cannabinoid receptors in lateral globus pallidus.
Selective neuronal vulnerability is a key feature of the neuropathology of Huntington's disease. We used [3H]CP-55,940, a synthetic cannabinoid, to label cannabinoid receptors in tissue sections from individuals dying with Huntington's disease and from normal control subjects. The density of cannabinoid receptors in striatum and pallidum was measured using quantitative autoradiography. There was a greater loss of cannabinoid receptors on striatal nerve terminals in the lateral pallidum compared to the medial pallidum, in Huntington's disease of all neuropathological grades. The disparity in binding density between the lateral and medial pallidum increased with higher grades of disease. There was also a greater loss of receptors in the lateral pallidum than in the putamen. The disproportionate loss of receptors in the lateral pallidum compared to the putamen increased in magnitude with severity of neuropathological grade. These data support the relative preferential loss or dysfunction of striatal neurons projecting to the lateral pallidum compared to neurons projecting to the medial pallidum. Terminals in the lateral pallidum containing cannabinoid receptors may be affected earlier or more severely than terminals in the medial pallidum, and both pallidal segments may be affected before or more severely than cell bodies or dendrites in the striatum. Terminal loss of markers may represent a response to perikaryal injury or dysfunction, or less likely, may indicate the primary site of neuronal damage in Huntington's disease.


Neutrophil elastase mediates acute pathogenesis and is a determinant of long-term behavioral recovery after traumatic injury to the immature brain.
While neutrophil elastase (NE), released by activated neutrophils, is a key mediator of secondary pathogenesis in adult models of brain ischemia and spinal cord injury, no studies to date have examined this protease in the context of the injured immature brain, where there is notable vulnerability resulting from inadequate antioxidant reserves and prolonged exposure to infiltrating neutrophils. We thus reasoned that NE may be a key determinant of secondary pathogenesis, and as such, adversely influence long-term neurological recovery. To address this hypothesis, wild-type (WT) and NE knockout (KO) mice were subjected to a controlled cortical impact at post-natal day 21, approximating a toddler-aged child. To determine if NE is required for neutrophil infiltration into the injured brain, and whether this protease contributes to vasogenic edema, we quantified neutrophil numbers and measured water content in the brains of each of these genotypes. While leukocyte trafficking was indistinguishable between genotypes, vasogenic edema was markedly attenuated in the NE KO. To determine if early pathogenesis is dependent on NE, indices of cell death (TUNEL and activated caspase-3) were quantified across genotypes. NE KO mice showed a reduction in these markers of cell death in the injured hippocampus, which corresponded to greater preservation of neuronal integrity as well as reduced expression of heme oxygenase-1, a marker of oxidative stress. WT mice, treated with a competitive inhibitor of NE at 2, 6 and 12h post-injury, likewise showed a reduction in cell death and oxidative stress compared to vehicle-treated controls. We next examined the long-term behavioral and structural consequences of NE deficiency. NE KO mice showed an improvement in long-term spatial memory retention and amelioration of injury-induced hyperactivity. However, volumetric and stereological analyses found comparable tissue loss in the injured cortex and hippocampus independent of genotype. Further, WT mice treated acutely with the NE inhibitor showed no long-term behavioral or structural improvements. Together, these findings validate the central role of NE in both acute pathogenesis and chronic functional recovery, and support future exploration of the therapeutic window, taking into account the prolonged period of neutrophil trafficking into the injured immature brain.


Antibacterial activity of cyclo(L-Pro-L-Tyr) and cyclo(D-Pro-L-Tyr) from Streptomyces sp. strain 22-4 against phytopathogenic bacteria.
Two bioactive cyclic dipeptides, cyclo(L-Pro-L-Tyr) and cyclo(D-Pro-L-Tyr), were isolated from the culture broth of Streptomyces sp. strain 22-4 and tested against three economically important plant pathogens, Xanthomonas axonopodis pv. citri, Ralstonia solanacearum and Clavibacter michiganensis. Both cyclic dipeptides were active against X. axonopodis pv. citri and R. Solanacearum with MIC of 31.25 μg/mL. No activity could be observed against C. michiganensis.


IP3R-mediated Ca2+ release regulates protein metabolism in Drosophila neuroendocrine cells: implications for development under nutrient stress.
Successful completion of animal development is fundamentally reliant on nutritional cues. Surviving periods of nutritional insufficiency requires adaptations that are coordinated, in part, by neural circuits. As neuropeptides secreted by neuroendocrine (NE) cells modulate neural circuits, we investigated NE cell function during development under nutrient stress. Starved Drosophila larvae exhibited reduced pupariation if either insulin signaling or IP3/Ca2+ signaling were downregulated in NE cells. Moreover, an IP3R (inositol 1,4,5-trisphosphate receptor) loss-of-function mutant displayed reduced protein synthesis, which was rescued by overexpression of either InR (insulin receptor) or IP3R in NE cells of the mutant, suggesting that the two signaling pathways might be functionally compensatory. Furthermore, cultured IP3R mutant NE cells, but not neurons, exhibited reduced protein translation. Thus cell-specific regulation of protein synthesis by IP3R in NE cells influences protein metabolism. We propose that this regulation helps developing animals survive in poor nutritional conditions.


Highly stable Q-switched and mode-locked pulse generation from an all-PM figure-9 fiber laser.
A highly stable figure-9 Yb-doped fiber laser with all polarization-maintaining (PM) double-cladding fiber is demonstrated. Through leveraging the saturable absorption effect of a nonlinear amplifying loop mirror, both the Q-switched and mode-locked operation are realized by adjusting the pump power. With increasing the pump power from the threshold to the maxima, the repetition rate of the Q-switched pulses is linearly increased from 14.9 kHz to 138.0 kHz with the pulse duration accordingly reduced from 3.9 µs to 970 ns. The corresponding maximum average power and pulse energy are respectively 2.34 W and 17 µJ, which are more than ten times larger than the common material-based Q-switched all-fiber lasers. In addition, in the process of increasing and decreasing the pump power, an optical bistability that manifested as a significant power jumping effect is observed, while its effect on the pulse repetition rate and duration is trivial. Whereas for the single pulse mode-locked operation, a maximum output power of 56.3 mW with a fundamental repetition rate of 12.5 MHz is realized, corresponding to a pulse energy of 4.5 nJ. To the best of our knowledge, it is much higher than the most of previous works concerning figure-9 all-PM-fiber lasers of which the emitted pulse energy is generally less than 1 nJ. After being compressed by a pair of diffraction grating, a minimum pulse width of 378 fs and a maximum peak power of 9.76 kW are respectively obtained. In addition, through characterizing the spectral and temporal properties of the laser source, the excellent stability of both the Q-switched and mode-locked operations is verified.


Dielectric response from lattices of dipoles with fixed orientation.
The properties of dipolar cubic lattices are studied and the paradox of how to obtain a long range polarization in such lattices is resolved by choosing a proper shape of the total system. It has been shown that large but finite number of aligned dipoles prefer to exist as needle shaped macroscopic particles [M. Yoon and D. Tománek, J. Phys.: Condens. Matter 22, 455105 (2010)]. The total energy for a particle in such a system has one short range contribution depending on the packing (the chosen lattice) and one long range term depending on the dipole density of the system. We show that the latter term corresponds exactly to the polarization term from a dielectric medium embedding a sphere of the considered system. There is no need to include a dielectric medium in this modeling and the "dielectric stabilization" is generated solely by the dipoles of the system.