Preclinical evaluation of ZD1839 alone or in combination with oxaliplatin in a panel of human tumor cell lines -- implications for clinical use.
Preclinical studies have suggested antitumor activity of an epidermal growth factor (EGF)-receptor targeted therapy with selective tyrosine kinase inhibitors alone or in combination with conventional cytostatic drugs. However, in non-small cell lung cancer (NSCLC), addition of ZD1839 (Iressa) to combination chemotherapy did not improve the therapeutic outcome. Thus, further work is necessary to define factors predicting outcome of combination therapy. In the present study, the activity of ZD1839 alone or in combination with oxaliplatin (Eloxatin) was evaluated in 12 human cancer cell lines including colon, testicular, anaplastic thyroid and epidermoid carcinoma cells. The EGF-receptor protein was overexpressed in line A431 (epidermoid carcinoma) and near the minimum detection limit in all other cell lines. The single agent activity of ZD1839 was highest in cell line A431. In the other cell lines, it was lower and appeared to be independent of EGF-receptor expression levels. The relative antitumor activity (RAA) was low (RAA = 1). Combined exposure to oxaliplatin and ZD1839 (IC30) resulted in significant synergy in 4 out of 6 colorectal cancer (CRC) cell lines and significant antagonism in 4 out of 6 non-colorectal cancer cell lines. Continuous exposure to ZD1839 (IC30) induced a marked G1-phase arrest and dephosphorylation of EGF-receptor in A431, whereas no significant cell cycle perturbation could be detected in the low-expression cell lines. Other factors than cell cycle perturbation seem to determine the mode of drug interaction between oxaliplatin and ZD1839. Based on RAA, the single agent activity of ZD1839 in the investigated cell line panel appeared to be low. Combined exposure to ZD1839 and oxaliplatin exerted synergy in colorectal cancer cell lines, warranting further evaluation in this type of cancer. However, based on the observed antagonism in non-colorectal cancer cell lines, combined treatment with ZD1839 and oxaliplatin is not recommended for other types of cancer. Further research is necessary to identify factors which determine the nature of drug interaction in different tumor types including CRC and lung cancer.


Prevalence, Impact, and Management Practice of Dysmenorrhea among University of Gondar Students, Northwestern Ethiopia: A Cross-Sectional Study.
Dysmenorrhea is an important health problem of adolescents in school, as well as health practitioners, that badly affects the daily activities and quality of life. The aim of this study was to measure the prevalence of dysmenorrhea and assess its management practice among University of Gondar students. A cross-sectional study was done from April 06 to May 08, 2016, on female students of University of Gondar. Descriptive and binary logistic regression analyses were used to describe and assess the association between different variables. More than two-thirds (75.3%) of the respondents were nonmedical students and the prevalence of dysmenorrhea was 77.6%. About half (50.6%) of the participants reported that they have a family history of dysmenorrhea and experienced continuous type of pain (53%) which lasts 1-2 days (47.8%). Abdominal spasm (70.4%), back pain (69.7%) fatigue, and weakness (63.5%) were the most commonly experienced dysmenorrhea symptoms. More than half (63%) of the respondents had encountered social withdrawal and decrease in academic performance (51.4%). More than two-thirds (63.8%) of the respondents use home remedies as a primary management option. Ibuprofen and diclofenac were the most commonly used medications to manage dysmenorrhea. The present study revealed that high proportion of University of Gondar female students had dysmenorrhea. Findings suggest the need for educating adolescent girls on appropriate and effective management of dysmenorrhea.


Predictors of mortality among the neonates transported to referral centre in Delhi, India.
A descriptive study was conducted with an objective to determine the predictors of mortality among referred neonates and to ascertain their transport characteristics. A total of 300 consecutive neonates who were transferred to the centre were enrolled in the study. Following information were recorded: maternal details, birth details, interventions before transportation, details of transportation and neonatal condition at arrival. Detailed clinical assessment and management was done as per standard neonatal protocols. Birth weight <1 kg (OR 0.04; 95% CI: 0.006-0.295, P<0.01) and transportation time >1 hour (OR 5.58; 95% CI: 1.41-22.01, P=0.01) were found to be significant predictors for mortality among the transported neonate. Transport characteristics reflect road transport with limited utility of ambulances and lack of trained health personal. Hence to conclude, extreme low birth weight and prolonged transportation time were found to be significant predictors of neonatal mortality among the transported neonate.


Contribution of brain-derived neurotrophic factor to mechanical hyperalgesia induced by ventral root transection in rats.
It is generally believed that the development of neuropathic pain primarily results from injuries to sensory afferent fibers. Recent studies found that injuries to the motor efferent fibers (e.g. ventral root transection) also contribute to the development of neuropathic pain. Furthermore, an increase in brain-derived neurotrophic factor (BDNF) synthesis has been found in the ventral root transection model, suggesting a possible role of BDNF in this model. To determine the role of BDNF, we observed the effects of intrathecal antibody against BDNF treatment on ventral root transection-induced mechanical hyperalgesia. Paw withdrawal thresholds to mechanical stimuli were measured before and after surgery. The results showed that ventral root transection in rats produced a significant, lasting decrease of mechanical withdrawal thresholds, presenting the development of mechanical hyperalgesia. Intrathecal antibody against BDNF treatment markedly inhibited ventral root transection-induced mechanical hyperalgesia in a dose-related manner. The findings suggest that BDNF-mediated signaling pathway within spinal cord may be involved in the development of neuropathic pain involving injuries to motor efferent fibers.


Nephrological and obstetric complications of the antiphospholipid syndrome.
The antiphospholipid syndrome (APS) is a disorder of hypercoagulability, characterised by thromboembolic events, repeated miscarriages and thrombocytopenia in association with circulating antiphospholipid antibodies. These antibodies are directed against epitopes on either oxidised phospholipids complexed with a glycoprotein, beta 2-glycoprotein I, or against the glycoprotein itself. Renal manifestations of the APS are varied and depend on the type of renal pathology present. The renal vasculature may be affected by either a small vessel, thrombotic microangiopathy process or by large vessel thrombosis. In patients with end stage renal disease, the prevalence of antiphospholipid antibodies may increase with time on dialysis. Anticardiolipin antibodies have been associated with a high incidence of haemodialysis access clotting, a major source of morbidity and hospitalisation in end stage renal disease patients. In renal transplant recipients, antiphospholipid antibodies may be associated with a higher incidence of primary graft non-function, particularly in patients without a history of pretransplantation haemodialysis. Complications of the APS during pregnancy span all trimesters and include intrauterine growth retardation, placental abruption, pre-eclampsia, preterm labour and recurrent fetal loss. As these women have a high risk of recurrent fetal loss, multiple treatment modalities have been investigated, including aspirin, heparin, prednisone and intravenous immunoglobulin. Various treatment strategies for the APS have been developed and are based on a combination of anticoagulant therapy with either warfarin or heparin, along with antiplatelet therapy with aspirin. Experimental treatments involving immunomodulatory therapy with intravenous immunoglobulin, apheresis and novel antibody therapy are being investigated with hopes of successful clinical applications.


An infrared scanning and tracking system for detecting mid-wave infrared spectral characteristics of moving targets.
This paper presents the design and fabrication of an infrared scanning and tracking system for detecting mid-wave infrared (MWIR) spectral characteristics of moving targets. The infrared spectra and infrared image are integrated in this system, which is mainly composed of a two-dimensional (2D) scanning mirror, dual-band infrared lens, long-wave infrared imaging unit, MWIR spectrum-measuring unit, and processing-controlling unit. After describing the design specifications of this system, this paper analyzes the detection method and then describes how the tracking was realized by controlling the 2D scanning mirror. Experiments were carried out to verify its feasibility.


ASSESSMENT OF PUPAL PRODUCTIVITY OF AEDES AND CO-OCCURRING MOSQUITOES IN KOLKATA, INDIA.
Monitoring of dengue vectors provide baseline information about the abundance and subsequent management strategy. An appraisal of mosquito abundance using dengue vectors as focal species was made in respect to Kolkata, India as geographical area. The data on immature abundance in the container larval habitats viz, earthen, porcelain and plastic materials were subjected to three-way factorial ANOVA, using months, habitats and species as variables. Similar tests were done on pupal weight and wing length. It was observed that Anopheles subpictus, Culex quinquefasciatus coexist with Ae. aegypti and Ae. albopictus in different container habitats, that varied with months and habitats. Ae. aegypti and Ae. albopictus were found in higher proportions in porcelain and plastic containers. In earthen containers a stable ratio of three mosquitoes was observed. Sex specific variations in pupal weight and wing length were noted in both species of Ae. aegypti and Ae. albopictus. The wing length of adult Aedes mosquitoes showed correspondence with pupal weight suggesting the use of pupal weight can be used as indicator of prospective adult body size. Although less known as container breeding, presence of An. subpictus and Cx. quinquefascistus along with Aedes indicates that availability of waste containers in environment increases risks of dengue and other mosquito borne diseases. The present habitat-based study calls for a strict vector management strategy to reduce the sources of ovipostion in various container habitats to minimize the mosquito vectors and thus potential risk of dengue and other mosquito borne diseases.


[On the constitutionality of tobacco regulation in Mexico].
As tobacco control legislation gains ground, public debate on the matter has come to be cast in constitutional terms. The present essay aims to provide information so as to participate in the debate in an informed manner. First, it explores the constitutional grounding for tobacco control. Then it analizes, one by one, the key arguments put forth to challenge the constitutionality ot tobacco control legislation, reaching the conclusion that none of the challenges holds water.


Dynamic length scales in glass-forming liquids: an inhomogeneous molecular dynamics simulation approach.
In this work, we numerically investigate a new method for the characterization of growing length scales associated with spatially heterogeneous dynamics of glass-forming liquids. This approach, motivated by the formulation of the inhomogeneous mode-coupling theory (IMCT) [Biroli, G.; et al. Phys. Rev. Lett. 2006 97, 195701], utilizes inhomogeneous molecular dynamics simulations in which the system is perturbed by a spatially modulated external potential. We show that the response of the two-point correlation function to the external field allows one to probe dynamic correlations. We examine the critical properties shown by this function, in particular, the associated dynamic correlation length, that is found to be comparable to the one extracted from standardly employed four-point correlation functions. Our numerical results are in qualitative agreement with IMCT predictions but suggest that one has to take into account fluctuations not included in this mean-field approach to reach quantitative agreement. Advantages of our approach over the more conventional one based on four-point correlation functions are discussed.


Differential regulation of collagen gene expression in granulation tissue and non-repair connective tissues in vitamin C-deficient guinea pigs.
Poor wound healing during vitamin C deficiency is thought to be due to decreased hydroxylation of proline residues in collagen. In non-repair connective tissues of guinea pigs, however, procollagen gene expression is not decreased until weight loss occurs during the third and fourth weeks of scurvy (phase II) with only a moderate decrease in proline hydroxylation. Decreased procollagen gene expression is related to the induction of insulin-like growth factor binding proteins 1 and 2 that inhibit insulin-like growth factor-I action. We examined wound healing and granulation tissue formation during phase I of vitamin C deficiency. Synthetic sponges were implanted on day 7 of vitamin C deficiency and analyzed at 6 and 10 days after surgery, when there was no weight loss or induction of insulin-like growth factor binding proteins. Healing of incisions was almost complete at 10 days after surgery in normal controls but not in scorbutic animals. The area around the incision and implant exhibited excessive angiogenesis and hemorrhaging of vessels in the scorbutic animals at 6 and 10 days after surgery. At 10 days after surgery, collagen synthesis in the implants of scorbutic guinea pigs was 36% lower than control values, with a normal extent of proline hydroxylation. Concentrations of messenger RNAs for types I and III procollagens were slightly increased by scurvy at 6 days after surgery but were decreased by 26% and 40%, respectively, at 10 days. Fibronectin mRNA levels were unaffected by scurvy at both time points. Our results suggest that poor wound healing in phase I of scurvy may be related to defective interstitial procollagen gene expression and defective blood vessel formation, but it does not involve inhibition of proline hydroxylation or induction of insulin-like growth factor binding proteins. mRNA for insulin-like growth factor-II, transforming growth factor-beta(1), and transforming growth factor-beta(2) were significantly expressed in implants, but their patterns of expression did not correlate with changes in procollagen gene expression.


[Enhancement of drug absorption by iontophoresis and phonophoresis and clinical application].
Concepts of iontophoresis and phonophoresis are described. Main factors regarding iontophoretic transdermal drug delivery of ionized drugs or non-ionized drugs and clinical applications are outlined. Iontophoretic and sonophoretic transdermal drug delivery has some advantages and disadvantages. However, its clinical use for controlled drug delivery corresponding to chronopharmacology will bring more benefit to patients in near future.


Improvement of the edge rotation diagnostic spectrum analysis via simulation.
The edge rotation diagnostic (ERD) system has been developed on the Joint Texas Experimental Tokamak to measure the edge toroidal rotation velocity by observing the shifted wavelength of carbon V (C V 227.09 nm). Since the measured spectrum is an integrated result along the viewing line from the plasma core to the edge, a method via simulation has been developed to analyze the ERD spectrum. With the necessary parameters such as C V radiation profile and the ion temperature profile, a local rotation profile at the normalized minor radius of 0.5-1 is obtained.


Choice of the surgical treatment in early gastric cancer.
The authors report their experience in choosing the surgical treatment for early gastric cancer. A retrospective study was conducted to examine the long-term outcome of 18 patients with early gastric cancer (10%) on a series of 180 patients treated for gastric carcinoma by the same surgical équipe from January 1986 to June 1997. Radical surgery with gastrectomy and extended lymphadenectomy ("regional" from 1986 to 1991; D2 from 1992 to 1997) was chosen as standard treatment for early gastric cancer except in elderly or high-risk patients and in cases of mucosal tumors diagnosed at definitive histology after surgery for benign diseases in which limited surgery was performed. All patients received curative (R0) surgery. One patient with mucosal-N1 tumor and another one with submucosal-N0 tumor died because of gastric cancer at 51 and 42 postoperative months respectively. The mean follow-up time was 99.8 (11-193) months. The overall 5-year and 10-year survival rates are 86.7% and 86.7% respectively. The 5- and 10-year survival rates for intramucosal tumors are 91% and 91% respectively and for submucosal cancer are 75% and 75% (P=0.39). According to the prognostic value of nodal involvement and the difficulty in achieving a preoperative accurate diagnosis of depth of invasion and of nodal involvement in early gastric cancer, a radical gastric resection with D2-lymphadenectomy should be performed.


Accurate and efficient calculation of van der Waals interactions within density functional theory by local atomic potential approach.
Density functional theory (DFT) in the commonly used local density or generalized gradient approximation fails to describe van der Waals (vdW) interactions that are vital to organic, biological, and other molecular systems. Here, we propose a simple, efficient, yet accurate local atomic potential (LAP) approach, named DFT+LAP, for including vdW interactions in the framework of DFT. The LAPs for H, C, N, and O are generated by fitting the DFT+LAP potential energy curves of small molecule dimers to those obtained from coupled cluster calculations with single, double, and perturbatively treated triple excitations, CCSD(T). Excellent transferability of the LAPs is demonstrated by remarkable agreement with the JSCH-2005 benchmark database [P. Jurecka et al. Phys. Chem. Chem. Phys. 8, 1985 (2006)], which provides the interaction energies of CCSD(T) quality for 165 vdW and hydrogen-bonded complexes. For over 100 vdW dominant complexes in this database, our DFT+LAP calculations give a mean absolute deviation from the benchmark results less than 0.5 kcal/mol. The DFT+LAP approach involves no extra computational cost other than standard DFT calculations and no modification of existing DFT codes, which enables straightforward quantum simulations, such as ab initio molecular dynamics, on biomolecular systems, as well as on other organic systems.


The generation of mature T cells requires interaction of the alpha beta T-cell receptor with major histocompatibility antigens.
THE T-cell repertoire within an individual is biased to recognize antigen in the context of self major histocompatibility complex (MHC) antigens. This is thought to depend on a process of positive selection during development. Support for this notion has recently been obtained in experiments using transgenic mice bearing genes for T-cell receptors (TCR) of defined specificity: T cells expressing the introduced genes form the main part of the mature T-cell population only in mice that express the appropriate MHC product. We have now extended these observations using TCR transgenic mice homozygous for the severe combined immunodeficiency (SCID) mutation which are defective in the rearrangement of both TCR and immunoglobulin genes. In this case mature thymocytes develop only in transgenic mice that express the MHC product which restricts the specificity of the transgenic TCR. This shows that the interaction of the alpha beta TCR with thymic MHC antigen is essential for the development of mature T cells. Furthermore, the peripheral lymph nodes of such mice are underdeveloped, suggesting that the peripheral expansion of mature T cells may require interactions with other lymphocytes expressing a range of receptors.


[Contribution of atrial activation to the segment of the typical atrial flutter wave: an electro-anatomic insight into the electrocardiogram morphology].
To investigate how the intra-cardiac activation was translates into the characterized flutter wave in patients with cavatricuspid isthmus-dependent counter-clockwise atrial flutter (CTI-AFL). A total of 15 hospitalized CTI-AFL patients (mean age: (60 ± 14) years old, 1 female) from October 2012 to February 2014 were enrolled in the study. The activation map was re-constructed during AFL rhythm for left atrium and right atrium using 3-dimensional mapping system. The flutter wave in surface electrocardiogram was analyzed in combination with the intra-cardiac activation. The mean left ventricular ejection fraction was (60.8 ± 6.6)%, and the left atrial diameter was (39.0 ± 3.4) mm. The mean tachycardia cycle length was (220 ± 24) ms. The activation map was completed in all cases. In inferior leads, the flutter wave was divided into three parts: slowly downward part, sharp downward part and the terminal positive part. The three parts corresponded to the fixed activation part of the macro-reentry. The distinctive flutter wave of CTI-AFL was determined by the unique macro-reentry activation in the right atrium. The activation of left atrium contributes to the downward part of the wave.


Estrogen effects on protein expressed by marrow stromal osteoblasts.
The aim of this study was to follow the changes of estrogen treatment on osteoblastic MBA-15 cells derived from marrow stromal origin. Following exposure to estrogen, the cells' patterns of protein synthesis and expression were monitored. The proteins synthesized by MBA-15 cells were identified in cell lysate fractionated to soluble proteins (SOL), cytoskeleton (CK), membrane and nuclei, and intermediate filaments (PL) fractions. These cellular fractions of the osteoblastic MBA-15 cell cultures were assayed on SDS-PAGE of total proteins or following radiolabeling of cells by [35S]-Methionine. Changes in cytoskeletal and membrane proteins of the control and treated cells were monitored by these assays. Reduction in expression of tubulin (TUB) and thropomyosin (TM) were observed by western blot analysis and of actin by fluorescein staining. A reduction in expression of an antigen highly expressed by osteogenic cells and detected by MoAb 85/12 was also observed in these cells. These experiments showed reduction in cytoskeletal and other cellular proteins in the stromal osteoblastic MBA-15 cells treated with 17beta-Estradiol in comparison to untreated cells.


The cyclooctatriene-eta2-ynyl potassium zwitterionic radical: evidence for a potassium organometallic.
Low-temperature (-120 degrees C) dehydrohalogenation of bromocyclooctatetraene (BrC8H7) with either sodium or potassium tert-butoxide followed by alkali metal reduction was used to generate the anion radical of [8]annulyne (C8H6*-) in tetrahydrofuran. EPR analysis at -120 degrees C reveals an extraordinarily large metal splitting when K or Cs (aK of 0.214 G and aCs of 3.26 G) serves as the reducing agent. The large aM is due to the metal cation interacting with the p-orbitals, within the alkyne moiety, that are in the plane of the ring system. The ionic radius of K+ is 1.33 A, which is larger than the B3LYP predicted distance between carbons 1 and 2 (1.23 A). However, the ionic radius of Na+ is only 0.95 A, and it is too small to simultaneously interact with both p-orbitals. Hence, no aM is observed when Na (ordinarily aNa > aK) or Li serves as the reducing agent. After the addition of 18-crown-6 to either the K or the Cs reduced system, two anion radicals are present. One is the system where the 18-crown-6 encapsulated metal complex is normally ion paired over the face of the ring system and aM = 0. The other is the cyclooctatriene-eta2-ynyl 18-crown-6 encapsulated metal zwitterion radical exhibiting a large aM. The ion pair to organometallic equilibrium constant is 1.6 +/- 0.1 and 3.5 +/- 0.1 for the K and Cs systems, respectively.


Protective effect of shen-fu injection on neuronal mitochondrial function in a porcine model of prolonged cardiac arrest.
Background. Shen-Fu injection (SFI) following cardiac arrest exhibits neurological effects, but its effect on neurological dysfunction is unclear. This study sought to investigate the protective effect of SFI on nerve cells in a porcine model of cardiac arrest. Methods. After eight minutes of untreated ventricular fibrillation (VF) and 2 minutes of basic life support, 24 pigs were randomized and divided into three cardiopulmonary resuscitation groups, which received central venous injection of either Shen-Fu (SFI group; 1.0 ml/kg), epinephrine (EP group; 0.02 mg/kg), or saline (SA group). Surviving pigs were sacrificed at 24 h after ROSC and brains were removed for analysis for morphologic changes of mitochondria by electron microscopy, for mitochondrial transmembrane potential (MTP) by flow cytometry, and for opening of the mitochondrial permeability transition pore (MPTP) by mitochondrial light scattering. Results. Compared with the EP and SA groups, SFI treatment reduced opening of MPTP, showing higher MMP. In addition, animals treated with SFI showed slight cerebral ultrastructure damage under the electron microscopy. Conclusion. Shen-Fu injection alleviated brain injury, improved neurological ultrastructure, stabilized membrane potential, and inhibited opening of MPTP. Therefore, SFI could significantly attenuate postresuscitation cerebral ischemia and reperfusion injury by modulating mitochondrial dysfunction of nerve cells.


Hyperglycemia-related FAS gene and hsa-let-7b-5p as markers of poor outcomes for ischaemic stroke.
Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia-associated genes can provide new avenues for stroke prognostic applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia-induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA-messenger RNA (mRNA) biomarkers in addition to using traditional risk factors. After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression. The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa-let-7b-5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system. Combined analyses of Fas and has-let-7b-5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia-induced stroke outcomes.


[Association between polymorphisms of interleukin-17 genes and pneumoconiosis susceptibility].
Objective: To explore the relationship between polymorphisms of interleukin 17(IL-17) gene (rs4711998, rs763780) and the susceptibility of pneumoconiosis, and to provide a basis for prevention of high-risk groups of pneumoconiosis. Methods: A total of 219 pneumoconiosis patients and 242 workers without pneumoconiosis were enrolled in the study. All subjects were photographed with high undulating X-rays anterior chest radiographs, diagnosed according to diagnostic criteria for pneumoconiosis. We collected 3 ml of peripheral venous blood of the study subjects. Polymorphism in IL-17A rs4711998 and IL-17F rs763780 locus were evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The IL-17A rs4711998 locus has AA, AG and GG genotypes, there was no the significant difference between case and control groups (P>0.05). IL-17F rs763780 had AA, AG and GG genotypes, there was a significant difference between case and control groups (P<0.05). Allele A and allele G were statistically significant difference between the case group and the control group (P<0.05). Conclusion: No relationship was found between IL-17A gene polymorphisms at rs4711998 and silicosis. IL-17F rs763780 locus gene polymorphism is associated with susceptibility to pneumoconiosis. AG genotype and G allele may have a protective effect.


Emerging roles of protein kinases in microglia-mediated neuroinflammation.
Neuroinflammation is mediated by resident central nervous system glia, neurons, peripherally derived immune cells, blood-brain barrier, and inflammatory mediators secreted from these cells. Neuroinflammation has been implicated in stroke and neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and amyotrophic lateral sclerosis. Protein kinases have been one of the most exploited therapeutic targets in the current pharmacological research, especially in studies on cancer and inflammation. To date, 32 small-molecule protein kinase inhibitors have been approved by the United States Food and Drug Administration for the treatment of cancer and inflammation. However, there is no drug effectively targeting neuroinflammation and/or neurodegenerative diseases. Recent studies have advanced several protein kinases as important drug targets in neuroinflammation and/or neurodegenerative diseases. Here, we review emerging protein kinases potentially involved in neuroinflammation and subsequent neurodegenerative diseases.


Use of the Ball-Cratering Method to Assess the Wear Resistance of a Welded Joint of XAR400 Steel.
Wear-resistant steels are designed to allow for operation under extreme loading conditions. They combine large strength with resilience and resistance to abrasive wear. In stock, the steel is subjected to preliminary heat treatment. However, any further processing at temperatures higher than 200 °C results in tempering that influences the mechanical properties of the material. The presented paper aims to study changes in abrasive wear properties across the welded joint made out of this steel, and its prime novelty lies in using the ball-cratering method to test the wear resistance of the joints. To distinguish between different crystalline structures in the weld, metallographic and XRD analyses were performed that resulted in the determination of five primary zones for which wear tests were carried out. Abrasive wear rates, studied across the welded joint, indicate that the material in the HAZ has the lowest resistance to abrasive wear. Similarly, the obtained values of the wear index show decreasing resistance of the material approaching the joint axis.


Multiple Sclerosis: Associations Between Physical Disability and Depression Are Not Mediated by Self-Reported Physical Activity.
This study investigated the interrelatedness of physical disability, physical activity, and depression among patients with multiple sclerosis (MS). We hypothesized that self-reported physical activity would mediate the effect of disability on depressive symptoms. Twenty-seven patients with MS (mean age: 49 years; 44.5% females) completed self-rating scales covering sociodemographic variables, intake of antidepressants, physical activity, and symptoms of depression; disability was measured by the Expanded Disability Status Scale. We found a higher level of disability to be significantly associated with more symptoms of depression. While higher reported physical activity was descriptively associated with lower depression scores and unrelated to Expanded Disability Status Scale, physical activity levels did not mediate the effect of disability on depressive symptoms.


[Goserelin plus anastrozole in the treatment of premenopausal patients with metastatic breast cancer].
To investigate the efficacy and safety of goserelin plus anastrozole in advanced premenopausal breast cancer patients. We summarized a single-centre experience with goserelin plus anastrozole in 32 premenopausal women with metastatic breast cancer (MBC). All patients received goserelin 3.6 mg by subcutaneous injection every 4 weeks concurrently with anastrozole 1 mg daily. The median duration of treatment was 12 months. No patient achieved complete remission (CR) (0%), 6 partial remissions (PR) (18.8%), 21 stable diseases (SD) (65.6%) and 5 progressive diseases (PD) (15.6%). Objective response rate (ORR) was achieved in 18.8% and clinical benefit (CR + PR + SD > 6 months) in 68.8%. The median progression-free survival (PFS) was 12 (2 - 57) months. One-year overall survival rate (OS) was 87.4% and two-year OS 66.9%. The OS of patients without visceral metastasis was significantly longer than that of patients with visceral metastasis (P = 0.04). Hot flushes and nausea were predominant toxicities. The combination of goserelin and anastrozole appears to be an efficient and well-tolerated regimen in premenopausal MBC women.


[Cortisol level and immunosuppression in viral hepatitis B in children and the approach to its treatment with glucocorticoids].
As many as 132 children with verified virus hepatitis were examined. Cortisol content in blood serum was measured and the parameters of cellular-humoral immunity were determined over time in the acute period and in the catamnesis up to 1 year. In the cyclic self-limiting forms of hepatitis B, the children developed immunologic unbalance with progressive hypercortisolemia, being an adequate reaction of the stressor systems and not requiring prednisolone administration. In protracted and chronic persistent hepatitis, the children developed immunosuppression and monotonous hypercortisolemia requiring short-term prednisolone treatment. The children afflicted with the grave and malignant forms of hepatitis B demonstrated, within the early times of the disease, secondary immunodeficiency and a considerable drop of cortisol content, demanding early prednisolone administration.


Generation of thiocillin ring size variants by prepeptide gene replacement and in vivo processing by Bacillus cereus.
The thiocillins from Bacillus cereus ATCC 14579 are natural products from the broader class of thiazolyl peptides. Their biosynthesis proceeds via extensive post-translational modification of a ribosomally encoded precursor peptide. This post-translational tailoring involves a key step formal cycloaddition between two distal serine residues. In the wild-type structure, this cycloaddition forms a major macrocycle circumscribed by 26-atoms (shortest path). Results presented herein demonstrate the promiscuity of this last step by means of a set of "competition" experiments. Cyclization proceeds in many cases to provide altered ring sizes, giving access to several variant rings sizes that have not previously been observed in nature.


Cost-Utility Analysis of Reconstruction Compared With Primary Amputation for Patients With Severe Lower Limb Trauma in Colombia.
To establish, from the health system perspective, the cost-utility relationship of limb reconstruction compared with primary amputation for patients older than 32 years with grade IIIB and IIIC severe lower limb trauma in Colombia, S.A. A Markov model was built including different short-term and long-term states that represent the main events that a patient could experience after a lower limb amputation or a reconstruction. A 42-year time horizon was considered for the base case. Transition probabilities were obtained from a systematic review of the clinical literature. The health outcome selected was the quality-adjusted life years. Costs were determined by expert consensus using the standard case methodology, and valuation of resources was conducted with national-level pricing manuals. Deterministic sensitivity, scenarios, and probabilistic analyses were conducted. In the base case, the reconstruction of the limb compared with primary amputation was a dominant strategy; that is, reconstruction provides more quality-adjusted life years at a lower cost. This result changed only when the time horizon was less than 6 years or when the probability of a secondary amputation was >65%. Limb reconstruction is a dominant strategy compared with primary amputation, which is a conclusion that holds in most scenarios this study examined. Therefore, it should be considered in patients who, according to the clinical criteria and the severity and characteristics of their trauma, can benefit from this technique. Economic Level II. See Instructions for Authors for a complete description of levels of evidence.


catena-Poly[copper(II)-{μ(3)-4,4'-dibromo-2,2'-[butane-1,4-diylbis(nitrilo-methanyl-yl-idene)]diphenolato-κN,O:N',O':O'}].
The asymmetric unit of the title coordination polymer, [Cu(C(18)H(16)Br(2)N(2)O(2))](n), consists of a Schiff base complex in which a crystallographic twofold rotation axis bis-ects the central C-C bonds of the n-butyl spacers of the designated Schiff base ligands, making symmetry-related dimer units, which are twisted around Cu(II) atoms in a bis-bidentate coordination mode. In the crystal, these dimeric units are connected through Cu-O bonds, forming one-dimensional coordination polymers, which propagate along [001]. The Cu(II) atom adopts a square-based pyramidal coordination geometry, being coordinated by two N and two O atoms of symmetry-related ligands and by a third O atom of a neighboring complex. Furthermore, inter-molecular π-π inter-actions [centroid-centroid distance = 3.786 (2) Å] and C-H⋯O inter-actions stabilize the crystal packing.


Laparoscopic surgery for pelvic organ prolapse.
There is growing interest in laparoscopic procedures for the correction of pelvic organ prolapse. The goals of prolapse surgery are to correct symptomatic pelvic floor defects and reestablish vaginal support resulting in the maintenance or restoration of normal visceral and sexual function. A thorough understanding of pelvic floor support as well as anterior abdominal wall and intra-abdominal, pelvic, and retropubic anatomy must be ascertained before attempting laparoscopic prolapse procedures. As many of these procedures require advanced laparoscopic skills and experienced surgeons, most of the literatures are comprised of case series by expert surgeons, with many of the studies centered on sacral colpopexies. However, the principles of laparoscopic prolapse surgery are based on open procedures and the only difference in the technique should be related to the route of operation; therefore, the efficacy of laparoscopic prolapse procedures should theoretically be comparable to their open abdominal counterparts.


Ribbing disease: a systematic review.
Background Ribbing disease, or multiple diaphyseal sclerosis, is a rare benign bone dysplasia. Purpose To systematically review the literature to determine the clinical and radiological presentation of patients with Ribbing disease as well as the effects of attempted treatments. Material and Methods We considered individual patient data of patients diagnosed with Ribbing disease derived from patient reports and patient series. All stages of the review were performed by two reviewers independently. Standard descriptive statistics were used for quantitative analyses and mixed model analyses were used when appropriate Results The literature search yielded 420 unique hits of which 23 studies were included, covering a total of 40 patients of whom 29 had bilateral involvement. The mean age at diagnosis was 35 years and the mean time between diagnosis and onset of symptoms, mostly pain, was five years (range = 1-16 years). The tibial diaphysis was the most commonly involved bone in 35 of 36 patients. Non-surgical treatment consisted of non-steroidal anti-inflammatory drugs (NSAIDs), prednisone, and bisphophonates with mixed results. Surgical treatment consisted of intramedullary reaming and fenestration and was very effective to reduce pain. Conclusion The clinical presentation and imaging findings of patients with Ribbing disease are becoming more apparent. However, there is paucity of evidence on the natural disease progression and effectiveness of treatment modalities.


TCNQ dianion-based coordination polymer whose open framework shows charge-transfer type guest inclusion.
A three-dimensional coordination framework constructed with 7,7,8,8-tetracyano-p-quinodimethane (TCNQ) diainon has been synthesized and structurally characterized. This open framework possessing a highly electron-rich surface has an optical sensing cavity for several aromatics with crystal-to-crystal transformation and strong accommodation, which are based on a charge-transfer interaction with them.


Effects of interrater reliability of psychopathologic assessment on power and sample size calculations in clinical trials.
Although rater training is increasingly used to improve the quality of the investigated outcome parameters, the reliability of assessments is not perfect. Thus, empirical reliability estimates should be used instead of theoretically assumed perfect reliability. Implications of the reliability of psychiatric assessments for sample size and power calculations in clinical trials are presented. The theoretical basis of sample size and power calculations using empirical reliability scores is delineated. Examples from contemporary research on schizophrenia and depression are used to illustrate several implications for study design and interpretation of results. The tremendous impact of the lack of reliability of psychopathologic assessments on sample size, power, and detectable true score differences in clinical trials is shown. The problem of multiple outcome variables with different reliabilities is addressed. Studies lacking power because of unreliable assessments carry the risk of false-negative findings and raise ethical questions. Rater training is strongly recommended to assess and improve interrater reliability whenever necessary and possible before trials are started. Sample size calculations and power analysis should be based on empirical reliability values of outcome parameters as part of quality assurance and cost savings.


Administration of Bifidobacterium bifidum BGN4 and Bifidobacterium longum BORI Improves Cognitive and Memory Function in the Mouse Model of Alzheimer's Disease.
Recent evidence indicates that gut microbiota could interact with the central nervous system and affect brain function, including cognition and memory. In this study, we investigated whether Bifidobacterium bifidum BGN4 (B. bifidum BGN4) and Bifidobacterium longum BORI (B. longum BORI) alleviated the pathological features in a mouse model of Alzheimer's disease (AD). Administration of B. bifidum BGN4 and B. longum BORI effectively suppressed amyloidosis and apoptotic processes and improved synaptic plasticity by ameliorating the neuroinflammatory response and BDNF expression. Moreover, behavioral tests indicated that B. bifidum BGN4 and B. longum BORI attenuated the cognitive and memory disability of AD mice. Taken together, the present study highlights the therapeutic potential of B. bifidum BGN4 and B. longum BORI for suppressing the pathological features of AD.


Role of cannabinoids in the management of neuropathic pain.
The treatment of pain, particularly neuropathic pain, is one of the therapeutic applications of cannabis and cannabinoids that is currently under investigation and that stimulates interest among clinicians and basic researchers. Animal pain models, including models of acute, antinociceptive, inflammatory and neuropathic pain, have demonstrated the antinociceptive efficacy of cannabinoids without causing serious alterations in animal behaviour. These data, together with the historic and current empiric use of cannabinoids, support the interest in the analysis of their effectiveness in treating neuropathic pain. The evaluation of controlled trials that focus on the effect of cannabinoids on neuropathic pain reveals that this class of drugs is able to significantly reduce pain perception. Nevertheless, this effect is generally weak and clinical relevance remains under evaluation. Moreover, there is a lack of controlled trials and, in particular, comparisons with other drugs generally used in the treatment of neuropathic pain. Despite the fact that further research is required to achieve a definitive assessment, current data obtained from basic research and from analysis of the available controlled trials indicate that cannabinoids can be accepted as a useful option in the treatment of neuropathic pain.


Vascular cell adhesion molecule-1 mediates lymphocyte adherence to cytokine-activated cultured human endothelial cells.
The expression and function of a new cytokine-induced endothelial cell adhesion protein, vascular cell adhesion molecule-1 (VCAM-1), was characterized in vitro by using a monoclonal antibody, MoAb 4B9, which recognizes a functional epitope on this protein. As determined by enzyme-linked immunosorbent assay and radioimmunoprecipitation of metabolically labeled cells, VCAM-1 was minimally expressed on unstimulated human umbilical vein endothelium (HUVE), but was rapidly induced by recombinant human tumor necrosis factor-alpha (rhTNF-alpha), rh interleukin-1, and lipopolysaccharide. In contrast to intercellular adhesion molecule-1, VCAM-1 was not induced on dermal fibroblasts or arterial smooth muscle cells after stimulation with rhTNF, or on keratinocytes after stimulation with rh interferon-gamma. MoAb 4B9 significantly inhibited the adherence of peripheral blood lymphocytes (PBL) and lymphocytic cell lines, but not neutrophils, to rhTNF-activated HUVE. The inhibitory effect of MoAb 4B9 on PBL adherence to HUVE was additive to that produced by the CD18 MoAb 60.3. These results show that VCAM-1 mediates a CD18-independent pathway of peripheral blood lymphocyte adherence to cytokine-stimulated HUVE. We propose that lymphocyte binding to VCAM-1, induced on endothelium by cytokines, may be an important component of lymphocyte emigration at sites of inflammation or immune reaction.


Screening for early detection of cardiovascular disease in asymptomatic individuals.
Primary prevention of cardiovascular disease has been aimed at risk factor identification and treatment without efforts to document early cardiovascular disease. The objective of the current study is to screen individuals with vascular and cardiac tests aimed at identifying early abnormalities likely to progress and to measure risk contributors susceptible to therapy. A center was established for comprehensive screening of an asymptomatic population with 10 tests designed to detect early vascular and cardiac abnormalities and blood tests to identify potential targets for risk contributor intervention. The first 396 individuals screened in the center have been analyzed. Using a scoring system from 0 (no disease) to 20 (advanced disease), 49% of the population exhibited scores of > or =5 and 39% exhibited scores of > or =6. These scores appear indicative of early disease mandating initiation of or change in medical therapy, which was recommended to the individuals screened and to their primary care physicians. The screening tests utilized are effective in uncovering unsuspected early cardiovascular disease in which targeted treatment could be effective in reducing the incidence of cardiovascular events in susceptible individuals. Documentation of the sensitivity and specificity of this approach requires longitudinal study.


Presence of Posterior Staphyloma in Congenital Cataract Children.
Purpose: To investigate the prevalence of posterior staphyloma (PS) in congenital cataract children and its role in predicting postoperative axial elongation.Materials and Methods: Preoperative prevalence of PS in 520 congenital cataract patients was reviewed and compared with that of the healthy eyes of 300 unilateral traumatic cataract children after 1:1 propensity score matching. Then, 32 pseudophakic children with preoperative PS and 48 age-matched pseudophakic controls without preoperative PS were followed up after the surgery, to compare their axial growth rates and refractive changes.Results: Congenital cataract was significantly associated with the presence of PS (OR: 14.88, P = .009) after propensity score matching. Even in congenital cataract eyes with axial length <26 mm, 5% were identified with PS on B-scan: ≤22 mm: 3%, 22-24 mm: 5% and 24-26 mm: 13%. Eyes with preoperative PS exhibited faster postoperative axial growth than those without, especially in bilateral cases or in children undergoing surgery before 8 years old (≤4 years: 0.53 ± 0.33 vs 0.30 ± 0.21 mm/y P = .028; 4-8 years: 0.37 ± 0.26 vs 0.23 ± 0.15 mm/y P = .044). Myopic shift after surgery was also more significant in children with preoperative PS than in those without (-1.10 ± 0.50 vs -0.60 ± 0.47D/y, P < .001).Conclusions: Congenital cataract is a risk factor for PS. Preoperative PS in pediatric cataract eyes may be an indicator of excessive postoperative axial elongation, especially in bilateral cases or in cases undergoing cataract surgery at a younger age. Our findings may also promote better clinical decision-making in intraocular lens power selection for pediatric population.


Mass Spectrometry in Cerebrospinal Fluid Uncovers Association of Glycolysis Biomarkers with Alzheimer's Disease in a Large Clinical Sample.
Alzheimer's disease (AD) is a complex heterogenous neurodegenerative disorder, characterized by multiple pathophysiologies, including disruptions in brain metabolism. Defining markers for patient stratification across these pathophysiologies is an important step towards personalized treatment of AD. Efficient brain glucose metabolism is essential to sustain neuronal activity, but hypometabolism is consistently observed in AD. The molecular changes underlying these observations remain unclear. Recent studies have indicated dysregulation of several glycolysis markers in AD cerebrospinal fluid and tissue. In this study, unbiased mass spectrometry was used to perform a deep proteomic survey of cerebrospinal fluid (CSF) from a large-scale clinically complex cohort to uncover changes related to impaired glucose metabolism. Two glycolytic enzymes, Pyruvate kinase (PKM) and Aldolase A (ALDOA) were found to be specifically upregulated in AD CSF compared to other non-AD groups. Presence of full-length protein of these enzymes in CSF was confirmed through immunoblotting. Levels of tryptic peptides of these enzymes correlated significantly with CSF glucose and CSF lactate in matching CSF samples. The results presented here indicate a general dysregulation of glucose metabolism in the brain in AD. We highlight two markers ALDOA and PKM that may act as potential functionally-relevant biomarkers of glucose metabolism dysregulation in AD.


Significant closure of the human immunodeficiency virus type 1 and hepatitis C virus preseroconversion detection windows with a transcription-mediated-amplification-driven assay.
While the present generation of serology-based assays has significantly decreased the number of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) infections acquired by transfusion, the possibility of infected donations escaping detection still exists. The average seronegative viremic window duration during which immunological assays are unable to detect the virus is estimated to be between 16 and 22 days for HIV-1 and approximately 70 days for HCV. Significant reduction of detection window duration was demonstrated using a nucleic acid amplification assay, the Procleix HIV-1/HCV Assay, which utilizes transcription-mediated amplification technology to simultaneously detect HIV-1 and HCV RNAs. For 26 commercially available HIV-1 seroconversion panels tested, specimens were reactive in the HIV-1/HCV assay at the same time as or earlier than in serological assays. Overall, the HIV-1/HCV assay was able to reduce the detection window duration by an average of 14 days and 6 days compared to tests relying on recognition of HIV-1 antibody and p24 antigen, respectively. For 24 commercially available HCV seroconversion panels tested, the specimens were reactive in the HIV-1/HCV assay at an earlier blood sampling date than in serological assays, reducing the detection window duration by an average of 26 days. Similar results were obtained in testing the HIV-1 and HCV seroconversion panels in the virus-specific HIV-1- and HCV-discriminatory assays, respectively. In conclusion, the HIV-1/HCV assay and corresponding discriminatory assays significantly reduced detection window durations compared to immunoassays.


Infantile Periocular Hemangioma.
Infantile periocular hemangiomas (IPH) are common benign vascular tumors that present early in childhood. They typically show a rapid nonlinear growth pattern a few weeks after birth during a proliferative phase, then continue with an involution phase and may result in serious ocular or systemic complications. Theses tumors may present in a range of small isolated lesions to multiple, diffuse involvements. Understanding the nature of the disease, the natural course, complications, indications for intervention, and treatment modalities would be helpful for ophthalmologists, who will likely be consulted for periocular cases. In this review, we present recent opinions about the pathogenesis, diagnosis, and treatment options for patients with IPH.


Kinetic analysis of chlorpropamide dissolution from solid dispersions.
Solid dispersions (SDs) of chlorpropamide were prepared by the solvent deposition technique using two grades of microcrystalline cellulose as carrier materials with different ratios of drug to carrier. The dissolution rate of chlorpropmide from the SDs was carried out at two physiological pH values of 1.1 and 7.25 simulating gastric and intestinal environments. The dissolution was dependent on the grade, the ratio of drug to carrier and pH. The higher dissolution was observed for more hydrophilic grade of the carrier as well as the higher ratio of carrier to drug. At the higher pH the drug dissolved much faster than the lower pH. X-ray diffraction showed some reduced drug crystallinity in SDs whereas infrared spectroscopy revealed no drug interactions with solvent and the carriers. The enhanced dissolution was attributed to the reduced drug crystallinity, decreased particle size, increased wettability and reduced aggregation of the hydrophobic drug particles. A novel model denoted as reciprocal powered time model with its theoretical justification was employed to analyze the dissolution data and proved to be superior to commonly used models for the analysis of the data. There was a quantitative relation between the model parameter and the ratio of carrier to drug which could be of value in dissolution rate prediction.


Skin lesions, differential diagnosis and practical approach to potential survivors of torture.
As the international refugee crisis has reached new proportions (BMJ, 355, 2016 and i5412), survivors of torture increasingly present in treating physicians with an array of acute or chronic skin lesions. Physicians should be aware of common presentations and likely differential diagnoses in order to avoid mislabelling or under-recognizing torture. Survivors of torture also frequently suffer from psychological sequelae, such as post-traumatic stress disorder, and appropriate referrals are essential in order to improve recovery trajectory. Skin sequelae are the most common physical findings of torture. Not all skin lesions seen in tortured survivors are due to perpetrator inflicted injuries, and many dermatological conditions can mimic lesions typical of torture, as can scars as a result of folk remedies or cultural practices specific to geographical regions. Medical documentation of torture includes injury and lesion description. While forensic dermatology and other forensic specialties use an injury description taxonomy, and the standard dermatologic taxonomy uses an anatomic description, they are complementary sciences for lesions inflicted by torture. This results in an opportunity for learning across disciplines in order to improve evidence documentation for survivors of torture. This article describes features of common skin lesions consistent with torture, including their clinical appearances, differential diagnoses, patterns of injury and appropriate clinical descriptions.


An affinity capture involved enzymatic assay for thrombin by using peptide aptamers as affinity ligands on magnetic beads.
Here we present a sensitive and specific assay for thrombin through the affinity capture of thrombin with mRNA display generated peptide aptamers on magnetic beads and the subsequent thrombin-involved enzymatic reaction. Thrombin at 50 fM can be detected.


Random resampling masks: a non-Bayesian one-shot strategy for noise reduction in digital holography.
Holographic imaging may become severely degraded by a mixture of speckle and incoherent additive noise. Bayesian approaches reduce the incoherent noise, but prior information is needed on the noise statistics. With no prior knowledge, one-shot reduction of noise is a highly desirable goal, as the recording process is simplified and made faster. Indeed, neither multiple acquisitions nor a complex setup are needed. So far, this result has been achieved at the cost of a deterministic resolution loss. Here we propose a fast non-Bayesian denoising method that avoids this trade-off by means of a numerical synthesis of a moving diffuser. In this way, only one single hologram is required as multiple uncorrelated reconstructions are provided by random complementary resampling masks. Experiments show a significant incoherent noise reduction, close to the theoretical improvement bound, resulting in image-contrast improvement. At the same time, we preserve the resolution of the unprocessed image.


Sedentary behaviours during pregnancy: a systematic review.
In the general population, at least 50% of time awake is spent in sedentary behaviours. Sedentary behaviours are activities that expend less energy than 1.5 metabolic equivalents, such as sitting. The amount of time spent in sedentary behaviours is a risk factor for diseases such as type 2 diabetes, cardiovascular disease, and death from all causes. Even individuals meeting physical activity guidelines are at a higher risk of premature death and adverse metabolic outcomes if they sit for extended intervals. The associations between sedentary behaviour with type 2 diabetes and with impaired glucose tolerance are stronger for women than for men. It is not known whether sedentary behaviour in pregnancy influences pregnancy outcomes, but if those negative outcomes observed in general adult population also occur in pregnancy, this could have implications for adverse outcomes for mothers and offspring. We aimed to determine the proportion of time spent in sedentary behaviours among pregnant women, and the association of sedentary behaviour with pregnancy outcomes in mothers and offspring. Two researchers independently performed the literature search using 5 different electronic bibliographic databases. Studies were included if sedentary behaviours were assessed during pregnancy. Two reviewers independently assessed the articles for quality and bias, and extracted the relevant information. We identified 26 studies meeting the inclusion criteria. Pregnant women spent more than 50% of their time in sedentary behaviours. Increased time in sedentary behaviour was significantly associated with higher levels of C Reactive Protein and LDL Cholesterol, and a larger newborn abdominal circumference. Sedentary behaviours were significantly higher among women who delivered macrosomic infants. Discrepancies were found in associations of sedentary behaviour with gestational weight gain, hypertensive disorders, and birth weight. No consistent associations were found between sedentary behaviour and other variables such as gestational diabetes. There was considerable variability in study design and methods of assessing sedentary behaviour. Our review highlights the significant time spent in sedentary behaviour during pregnancy, and that sedentary behaviour may impact on pregnancy outcomes for both mother and child. The considerable heterogeneity in the literature suggests future studies should use robust methodology for quantifying sedentary behaviour.


The use of projections for dimensionality reduction of flow cytometric data.
In order to visualize multiparameter flow cytometric measurements it is desirable to reduce the dimensionality of the data to two while preserving important features of each data pattern. We describe a method that projects two-parameter data onto a straight line that forms an angle theta with one of the original parameter axis. The angle is selected interactively or by principal component analysis. The procedure is applied on-line or off-line to pairs of parameters of the original data set that has been collected in LIST mode.


Neutrophil Membrane-Derived Nanovesicles Alleviate Inflammation To Protect Mouse Brain Injury from Ischemic Stroke.
Ischemic stroke is an acute and severe neurological disease, resulting in disability and death. Reperfusion to an ischemic brain is a means to reverse brain damage after stroke; however, this causes secondary tissue damage induced by inflammation responses, called ischemia/reperfusion (I/R) injury. Adhesion of neutrophils to endothelial cells underlies the initiation of inflammation in I/R. Inspired by this interaction, we report a drug delivery system comprised of neutrophil membrane-derived nanovesicles loaded with Resolvin D2 (RvD2) that can enhance resolution of inflammation, thus protecting brain damage during ischemic stroke. In the study, the middle cerebral artery occlusion (MCAO) mouse model was developed to mimic ischemic stroke. Using intravital microscopy of a live mouse brain, we visualized the binding of nanovesicles to inflamed brain vasculature for delivery of therapeutics to ischemic stroke lesions in real-time. We also observed that RvD2-loaded nanovesicles dramatically decreased inflammation in ischemic stroke and improved mouse neurological functions. Our study provides a strategy to inhibit neuroinflammation using neutrophil-derived nanovesicles for ischemic stroke therapy.


Stable isotope analysis reveals ontogenetic feeding shifts in Pacific blue marlin (Makaira nigricans) off eastern Taiwan.
To gain a better understanding of the trophic ecology of Pacific blue marlin Makaira nigricans off eastern Taiwan, nitrogen and carbon stable isotopes (δ15 N and δ13 C) and Bayesian mixing models were used to explore trophic dynamics and potential ontogenetic feeding shifts across M. nigricans of different size classes. Makaira nigricans samples from east of Taiwan (n = 213) and Palau (n = 37), as well as their prey (n = 70), were collected during 2012 and 2013. Results indicated increases in δ15 N with size, with values of larger size classes (> 200 cm eye-to-fork length; LEF ) significantly higher than those < 200 cm LEF . Values of δ13 C were negatively correlated with size. Makaira nigricans > 200 cm LEF had the highest estimated trophic position (4.44) and also exhibited ontogenetic changes in trophic position. Large M. nigricans fed more on dolphinfish Coryphaena hippurus and hairtail Trichiurus lepturus, while smaller M. nigricans consumed smaller forage fish (e.g., moonfish Mene maculata) and cephalopods. These changes may relate to greater swimming speeds and vertical habitat use in larger M. nigricans, allowing capture and consumption of larger prey items at higher trophic positions. The high trophic level of M. nigricans east of Taiwan confirms its important role as an apex predator in marine food webs and how ecological role changes with size.


Genotyping of Madurella mycetomatis by selective amplification of restriction fragments (amplified fragment length polymorphism) and subtype correlation with geographical origin and lesion size.
One of the causative organisms of mycetoma is the fungus Madurella mycetomatis. Previously, extensive molecular typing studies identified Sudanese isolates of this fungus as clonal, but polymorphic genetic markers have not yet been identified. Here, we report on the selective amplification of restriction fragment (AFLP) analysis of 37 Sudanese clinical isolates of M. mycetomatis. Of 93 AFLP fragments generated, 25 were polymorphic, and 12 of these 25 polymorphic fragments were found in a large fraction of the strains. Comparative analysis resulted into a tree, composed of two main (clusters I and II) and one minor cluster (cluster III). Seventy-five percent of the strains found in cluster I originated from central Sudan, while the origin of the strains in cluster II was more heterogeneous. Furthermore, the strains found in cluster I were generally obtained from lesions larger than those from which the strains found in cluster II were obtained (chi-square test for trend, P = 0.03). Among the 12 more commonly found polymorphisms, 4 showed sequence homology with known genes. Marker A7 was homologous to an endo-1,4-beta-glucanase from Aspergillus oryzae, 97% identical markers A12 and B3 matched a hypothetical protein from Gibberella zeae, and marker B4 was homologous to casein kinase I from Danio rerio. The last marker seemed to be associated with strains originating from central Sudan (P = 0.001). This is the first report on a genotypic study where genetic markers which may be used to study pathogenicity in M. mycetomatis were obtained.


Matrix metalloproteinases: role in arthritis.
The irreversible destruction of the cartilage, tendon, and bone that comprise synovial joints is the hallmark of both rheumatoid arthritis (RA) and osteoarthritis (OA). While cartilage is made up of proteoglycans and type II collagen, tendon and bone are composed primarily of type I collagen. RA is an autoimmune disease afflicting numerous joints throughout the body; in contrast, OA develops in a small number of joints, usually resulting from chronic overuse or injury. In both diseases, inflammatory cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) stimulate the production of matrix metalloproteinases (MMPs), enzymes that can degrade all components of the extracellular matrix. The collagenases, MMP-1 and MMP-13, have predominant roles in RA and OA because they are rate limiting in the process of collagen degradation. MMP-1 is produced primarily by the synovial cells that line the joints, and MMP-13 is a product of the chondrocytes that reside in the cartilage. In addition to collagen, MMP-13 also degrades the proteoglycan molecule, aggrecan, giving it a dual role in matrix destruction. Expression of other MMPs such as MMP-2, MMP-3 and MMP-9, is also elevated in arthritis and these enzymes degrade non-collagen matrix components of the joints. Significant effort has been expended in attempts to design effective inhibitors of MMP activity and/or synthesis with the goal of curbing connective tissues destruction within the joints. To date, however, no effective clinical inhibitors exist. Increasing our knowledge of the crystal structures of these enzymes and of the signal transduction pathways and molecular mechanisms that control MMP gene expression may provide new opportunities for the development of therapeutics to prevent the joint destruction seen in arthritis.


Research Progress on the Inflammatory Effects of Long Non-coding RNA in Traumatic Brain Injury.
Globally, traumatic brain injury (TBI) is an acute clinical event and an important cause of death and long-term disability. However, the underlying mechanism of the pathophysiological has not been fully elucidated and the lack of effective treatment a huge burden to individuals, families, and society. Several studies have shown that long non-coding RNAs (lncRNAs) might play a crucial role in TBI; they are abundant in the central nervous system (CNS) and participate in a variety of pathophysiological processes, including oxidative stress, inflammation, apoptosis, blood-brain barrier protection, angiogenesis, and neurogenesis. Some lncRNAs modulate multiple therapeutic targets after TBI, including inflammation, thus, these lncRNAs have tremendous therapeutic potential for TBI, as they are promising biomarkers for TBI diagnosis, treatment, and prognosis prediction. This review discusses the differential expression of different lncRNAs in brain tissue during TBI, which is likely related to the physiological and pathological processes involved in TBI. These findings may provide new targets for further scientific research on the molecular mechanisms of TBI and potential therapeutic interventions.


Characteristics of Decedents With COVID-19-Related Mortality in Kentucky, July 1-August 13, 2021.
Although vaccination reduces the risk of severe COVID-19, fatal COVID-19 cases after vaccination can occur. We examined the characteristics of decedents with COVID-19-related mortality to help inform discussions about vaccination, boosters, and mitigation strategies. We examined COVID-19-related deaths in Kentucky resulting from infections occurring from July 1 through August 13, 2021. We used records from case investigations, medical records, the Kentucky Health Information Exchange, and the Kentucky Immunization Registry to determine demographic information, vaccination status, and underlying health conditions, including calculation of the Charlson Comorbidity Index (CCI). We calculated mortality incidence rates by vaccination status by using data for unvaccinated and fully vaccinated populations in Kentucky as of July 1, 2021. In total, 777 COVID-19-related deaths occurred in Kentucky during the study period; 592 (76.2%) occurred among unvaccinated people. Compared with unvaccinated decedents, fully vaccinated decedents were older (median age, 77 vs 65 years; P < .001), had higher comorbidity levels (median CCI, 3 vs 1; P < .001), and were more likely to have immunocompromised health status (26.4% vs 16.0%; P = .003). Diabetes, hypertension, heart disease, and chronic lung disease were more common among vaccinated decedents than among unvaccinated decedents. Unvaccinated adults had a significantly higher risk of death than fully vaccinated adults (incidence rate ratio for age 20-49 years: 20.5 [95% CI, 6.5-64.8]; 50-64 years: 14.6 [95% CI, 9.4-22.7]; ≥65 years: 10.2 [95% CI, 8.3-12.4]). Immunocompromised health status, older age, and higher comorbidity were prevalent among fully vaccinated decedents, suggesting adults with these characteristics may benefit from additional protection strategies. Further understanding of the protection of additional and booster doses is needed.


Preventing and modulating learned wound pain.
Wounds cause pain but the consequences of wound pain remain largely unknown. Studies from other disciplines have shown that pain can contribute to the long-term physiological and emotional consequences of the pain experience, setting the stage for the phenomenon referred to as "learned pain." Providing ways to help patients avoid learning pain--ie, modulating pain anticipation/expectation, peripheral nerve blocks, pretreatment analgesics, biophysical technologies, modification of patient and provider behavior, judicious choice of dressings, and behavioral therapies--has been found to play a significant role in decreased physical and emotional discomfort and improved outcomes. Existing evidence on pain suggests that wound pain most likely consists of a combination of local, systemic, and learned phenomena retained by the patient as long-term "pain memories" as well as acute reaction to stimuli. Until the consequences of wound pain are fully appreciated, healthcare providers should consider application of research findings from other disciplines to reduce pain and prevent the learning and development of pain memories.


A long-term open-label study of oral almotriptan 12.5 mg for the treatment of acute migraine.
Evaluate the long-term tolerability of almotriptan 12.5 mg for the treatment of acute migraine attacks occurring over a 6-month period. Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular selectivity for meningeal arteries and has demonstrated efficacy for the treatment of acute migraine in short-term controlled trials. This was a 6-month open-label study. Adults (18 years of age or older) were required to have a diagnosis of acute migraine with or without aura (according to the diagnostic criteria of the International Headache Society), a history of at least 1 year of moderate-to-severe migraine pain with at least two and a maximum of six migraines per month, and at least 24 hours of freedom from head pain between attacks. Patients were instructed to take a single 12.5-mg dose of almotriptan at the onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape medication could be taken; if relapse occurred in less than 24 hours, a second 12.5-mg dose could be taken. Tolerability was assessed from the nature and incidence of all adverse events, and efficacy was assessed according to the end point of pain relief 2 hours following almotriptan administration. Of 585 patients treated, 582 were included in the intent-to-treat population. The most frequent drug-related adverse events were nausea (3.1%) and dizziness (2.4%). No serious drug-related adverse events were reported, and no deaths occurred. Adverse events led to discontinuation of treatment in 36 patients (6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six percent of patients achieved pain relief at 2 hours for all attacks treated, and 49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and pain-free rates were higher among those with moderate baseline pain. When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and effective for the long-term treatment of acute migraine.


NEUROLOGIC AND COMPUTED TOMOGRAPHY FINDINGS IN SEA TURTLES WITH HISTORY OF TRAUMATIC INJURY.
Boat strikes have been widely documented as a major cause of anthropogenic trauma and mortality in sea turtles. Axial trauma in these species involves the head and/or carapace and may cause severe damage to the nervous and pulmonary systems. The aims of this study were to develop an updated protocol for neurologic examinations in sea turtles, to describe computed tomography (CT) findings in sea turtles with sustained trauma, and to associate CT findings with neurologic status in sea turtles with and without traumatic injury. Ten sea turtles were examined, six green (Chelonia mydas) and four loggerhead (Caretta caretta) turtles: seven underwent neurologic and CT examinations, two had CT examinations only, and one had a neurologic examination only. The updated neurologic examination protocol was considered useful in differentiating normal from abnormal neurologic status, however some of these tests remain unreliable in sea turtles. Sea turtles with no history of trauma were found to have normal carapace shape, vertebral column, and neurologic status. Sea turtles with history of traumatic injury (more than 10 years prior to examination) had findings dependent on trauma site. Those with head trauma had variable presentations dependent on location of injury; while those with carapace trauma had varying degrees of kyphosis, lordosis, and scoliosis of the carapace, vertebral fractures, and paraparesis. Kyphosis of the carapace was associated with vertebral fractures detected on CT; however, the severity of vertebral abnormalities was not associated with the severity of neurologic deficits. These findings suggest that a combination of neurologic and CT examination may be beneficial in determining clinical significance of carapace deformation and associated neurologic deficits in sea turtles with traumatic injury.


Versatile Red Blood Cells for Triple-Negative Breast Cancer Treatment via Stepwise Photoactivations.
Phototherapies have many advantages for triple-negative breast cancer (TNBC) treatment. However, their effects are often limited by short blood circulation time, poor tumor selectivity and weak penetration of phototherapeutic agents, and tumor hypoxia. For overcoming these limitations, a versatile biomimetic system is developed based on red blood cells (RBCs). Photothermal agent new indocyanine green (IR820) is conjugated with the cell/tissue-penetrating TAT peptide and further efficiently encapsulated into the intact RBCs by crossing cell membranes to realize the long blood circulation. Meanwhile, cyclic RGD peptide (cRGD) is linked to the surfaces of RBCs through phospholipid insertion to obtain tumor vessel-targeting ability. Photosensitizer temoporfin (mTHPC) is next loaded into the membranes of RBCs by spontaneous transferring. The acquired biomimetic system (cRGD-RBC@mTHPC/TAT-IR820) exhibits potent photodynamic performance upon 652 nm laser irradiation with the facilitation of oxyhemoglobin, which could not only trigger TAT-IR820 release but also destroy tumor vessels. TAT-IR820 penetrates deeply into tumor tissue via the mediation of TAT peptide, exerting greatly promoted photothermal ablation against TNBC upon 808 nm laser irradiation. In situ generated tumor antigens further induce robust immune responses to suppress TNBC recurrence and metastasis. In summary, this study provides a versatile biomimetic system for comprehensive TNBC treatment via stepwise photodynamic and photothermal activations.


Observation of Rapid Adiabatic Passage in Optical Four-Wave Mixing.
We observe clear evidence of adiabatic passage between photon populations via a four-wave mixing process, implemented through a dispersion sweep arranged by a core diameter taper of an optical fiber. Photonic rapid adiabatic passage through the cubic electric susceptibility thus opens precise control of frequency translation between broadband light fields to all common optical media. Areas of potential impact include optical fiber and on-chip waveguide platforms for quantum information, ultrafast spectroscopy and metrology, and extreme light-matter interaction science.


Voice pathology detection using optimized convolutional neural networks and explainable artificial intelligence-based analysis.
This article proposes a noninvasive computer-aided assessment approach based on optimized convolutional neural network for healthy and pathological voice detection. Firstly, the input voice samples are first transformed into mel-spectrogram time-frequency visual representations and fed for training the CNN model. The time-frequency image captures inherent speech variations beneficial for healthy and pathological voice sample detection. The weights and biases of trained CNN network are further optimized using artificial bee colony (ABC) optimization algorithm resulting in optimum CNN network employed for testing unseen data. The proposed approach is evaluated using three popular and publicly available datasets: SVD, AVPD and VOICED. Experimental results emphasize that proposed ABC optimized CNN model shows improved accuracy performance by 1.02% compared to conventional CNN network illustrating data-independent discriminative representation ability. Finally, gradient-weighted class activation mapping (Grad-CAM) explainable artificial intelligence (XAI) is utilized to make the decision understandable.


Functional characterization, sequence comparisons and distribution of a polyketide synthase gene required for perithecial pigmentation in some Fusarium species.
Polyketides are a structurally diverse class of secondary metabolites produced by bacteria, fungi, plants and animals. The fungal genus Fusarium includes agronomically important plant pathogenic and mycotoxin-producing species and produces numerous polyketides. The study further characterized a polyketide synthase-encoding gene (PKS3 = PGL1) that was previously identified in F. graminearum and F. verticillioides. Disruption of the F. verticillioides PGL1 indicated that it is required for the production of the dark pigment in perithecial walls, as previously shown in F. graminearum. A third PGL1 orthologue was identified in the genomic sequence of N. haematococca (anamorph F. solani f. sp. pisi). Analysis of the carboxy-terminal end of the deduced PGL1 protein indicated that it had a functional domain related to dehydrogenases/reductases that is sometimes present in non-ribosomal peptide synthetases. Comparison of the genomic regions flanking PGL1 in F. graminearum, F. verticillioides and N. haematococca revealed that the extent of gene synteny in this region was greater between F. graminearum and F. verticillioides than between either of these species and N. haematococca. Southern blot analysis indicated that PGL1 occurs widely within the genus Fusarium including species with no known sexual stage.


Repair of potentially lethal damage by introduction of T4 DNA ligase in eucaryotic cells.
The bacterial enzyme PvuII, which generates blunt-ended DNA double-strand breaks, and T4 DNA ligase, which seals adjacent DNA fragments in coupling to ATP cleavage, were introduced in mouse C3H10T1/2 fibroblasts using osmolytic shock of pinocytic vesicles. Cells were then assayed for their clonogenic ability. In agreement with previous studies by others, we find that the PvuII restriction endonuclease simulates ionizing radiation effects by causing a dose-dependent loss of reproductive capacity. Here we show that the concomitant treatment with DNA ligase considerably increases cell survival. Survival curves were shown to be dependent on the ligase enzyme dose and on ATP concentration in the hypertonic medium. We conclude that T4 DNA ligase is able to repair some of the potentially lethal damage produced by restriction endonucleases in eucaryotic cells.


Eating habits and dietary acculturation effects among international college students in the United States.
Although the United States rates as the top host country for international students in the world, the impact of dietary acculturation on their health status is poorly understood. This study used a qualitative approach to gain an in-depth understanding of the factors related to dietary acculturation among international students in U.S. universities. Ten focus groups, of which eight were in two Midwestern U.S. universities and two in a Southern U.S. university (n = 44), were studied. Participants were international, college-aged students enrolled in U.S. universities. Grounded theory method was used for data analysis to develop themes relevant to dietary changes and factors related to dietary acculturation based on the participants' perspectives and experiences. The results showed that most of the participants faced various dietary challenges and health consequences in the United States. Access to food, religious orientation, time constraints, campus environment, and healthcare access were the main factors influencing student diets. A majority of the students reported weight gain due to eating larger portions, unstructured mealtimes, and frequent snacking. Some students reported that they do not eat fruits and vegetables in the United States because they believe that these foods are not fresh, genetically modified, and may contain pesticides. The majority of participants reported taking unprescribed dietary supplements since moving to the United States. Students who transitioned to the typical American diet reported weight gain, increased fatigue, abdominal discomfort, and other health consequences. Universities should seek to develop policies and programs aimed to reduce the impact of acculturation in order to improve the experience of international students in the United States.


[Triterpenes and steroidal compounds from Momordica dioica].
Three triterpenes and two steroidal compounds were isolated from the dry root of Momordica dioica. Their structures were elucidated by spectral analyses (MS, IR, 1HNMR, 13CNMR and DEPT) and chemical methods. These compounds are alpha-spinasterol octadecanonate(I), alpha-spinasterol-3-O-beta-D-glucopyranoside(II), 3-O-beta-D-glucuronopyranosyl gypsogenin(III), 3-O-beta-D-glucopyranosyl gypsogenin(IV) and 3-O-beta-D-glucopyranosyl hederagenin(V). Constituent III is a new compound. The CHCl3 extract of Momordica dioica roots and five isolated constituents showed anticancer activity in pharmacologic testing on cancer cell(L1210). The growth inhibitory index(%) of compound II was shown to be 50%, at the dose of 4 micrograms.ml-1.


Continuity in the midst of change: behaviors of residents relocated from a nursing home environment to small households.
A time-sampling procedure was used to observe behaviors of 22 long-term-care residents with dementia (Mini-Mental State Exam median, 11.94; range 0-23) in public areas before and after relocation from a traditional nursing home environment to 2 small household units. Two trained observers noted the occurrence of 19 social behaviors (14 verbal, 5 nonverbal) in which the resident intentionally interacted with another person. Another 19 nonsocial behaviors (16 active, 3 passive) were also coded. Analysis by t tests of 6 groupings of behaviors showed no significant differences before and after relocation, with the exception of nonverbal social interactions. Overall, residents showed consistency in both social and nonsocial behaviors. Results are interpreted in light of personal, social, and environmental continuity despite the many changes associated with the relocation.


Interfacial interactions between poly[L-lysine]-based branched polypeptides and phospholipid model membranes.
The interaction of five poly[L-lysine]-derived branched chain polypeptides of poly[Lys(X(i))] (X(i)K) or poly[Lys(X(i)-DL-Ala(m))] (XAK) with lipid bilayers (DPPC and DPPC/PG, 8:2) was studied by fluorescence polarization techniques. Two fluorescent probes, DPH and TMA-DPH, were utilized to monitor changes of motion in the internal and/or in the polar head regions, respectively. Results indicate that the interaction of polypeptides with neutral (DPPC) bilayers is mainly dependent on the polarity and electrical charge of side chains. The amphoteric E(i)K shows the highest level of interaction. Polycationic polypeptides (H(i)K, P(i)K, TAK) have a relatively small effect on the transition temperature of the lipids, while the polyanionic Succ-EAK has no effect at the alkyl chain region of the bilayer. Data with TMA-DPH indicate the lack of pronounced interaction between the polypeptides and the outer surface of the liposome. Similar tendency was documented for DPPC/PG vesicles. Polypeptides, H(i)K, and P(i)K induce significant changes in the transition temperature, thus indicating their insertion into the hydrophobic core of the bilayer without marked effect on the polar head region. Results suggest that these polypeptides (except E(i)K) have no destabilizing effect on liposomes studied. These properties are considered as beneficial for their use as safe carriers for bioactive molecules.


Outcome of patients with cleft lip and cleft palate operated at Mahosoth, Mitthaphab and Setthathirath Hospitals in Lao People's Democratic Republic.
Cleft lip and cleft palate or both are the most common orofacial congenital malformations found among live births. The causes of which are not clear but have a trend that includes 2 etiological factors, genetic and environmental. The incidence rate of cleft lip and palate is similar in every country worldwide and it stands at approximately 1-2/1,000 newborn. For instance, it is 1.09/1,000 in India, South Korea and Thailand. Estimate, in Lao PDR could be 0.02/1,000 newborn. Cleft lip and cleft palate and craniofacial anomalies are congenital defects with numerous sequels in dental, speech, hearing, body-image and psychosocial realms. Cleft lip and palate operation is still limited in many parts of Lao PDR. To study the outcome of patients with cleft lip and cleft palate, particularly the nasolabial appearance and quality of life, who were operated in Lao People 's Democratic Republic. The present study was reviewed and approved by the Ethics for Human Research, Khon Kaen University in Thailand and National Ethics Committee for Health Research in Lao PDR. This was a cross-sectional study of 50 persons who were chosen as samples and were divided into two age groups, group A, which included subjects between 5 and 15 years of age (31 persons) and group B composed of those above 15 years (19 persons). Data collection was done by means of a questionnaire and the latter was divided into three main headings: demographic characteristics, quality of life and nasolabial appearance. The list of patients with cleft lip and palate was obtained from the 3 Hospitals in Vientiane, the capital, and then entered directly as samples. Demographic data and quality of life were analyzed by means of percentage, frequency, mean and standard deviation with the help of SPSS for Window. Similarly, inter-rater reliability using kappa statistics was done for the evaluation of nasolabial appearance. The inter-rater reliability for Nasolabial appearance was 0.2044 or 20.44% (p-value <0.0001). Average score in each dimension of nasolabial appearance (nasal form, nasal symmetry, vermillion border nasolabial profile) are scored 3.15, 3.13, 3.35 and 3.06 respectively. This placed it on fair level (3.17point). The quality of life: group (A) and (B) were whose have the quality of life on fair to good level for mentalities and satisfaction on fair level that is comparable. The result of the research revealed that the rating of reliability of inter-rater was rather low. However each dimension of quality of life of both groups was at fair level.


Developing Children's Creativity and Social-Emotional Competencies through Play: Summary of Twenty Years of Findings of the Evidence-Based Interventions "Game Program".
This work presents the results of four cooperative-creative game programs (Game Programs). In all four studies, experimental designs with repeated pretest-posttest measures and control groups were used. Validation samples ranged from 86 to 178 participants, randomly assigning participants to the experimental and control conditions. Before and after each program, a battery of assessment instruments was applied to measure the variables under study. The intervention consists of conducting a weekly game session during the school year. The results of the posttest covariance analyses confirmed a significant impact: (1) in social development, by increasing various positive social behaviors and decreasing many negative social behaviors; by increasing assertive cognitive strategies and prosocial resolution of interpersonal problems; and by enhancing relationships and positive communication among group members; (2) in emotional development, by improving self-concept, peer image, and emotional stability; and (3) in cognitive development, by increasing verbal intelligence, verbal and graphic-figurative creativity, as well as creative personality behaviors and traits. This work provides empirical evidence of the relevance of cooperative-creative play in child development.


Tobacco User Characteristics and Outcomes Related to Intensity of Quitline Program Use: Results From Minnesota and Pennsylvania.
Tobacco users in all 50 states have access to quitline telephone counseling and cessation medications. While studies show multiple calls relate to quit success, most participants do not complete a full call series. To date, quitline program use studies have analyzed single factors-such as number of calls or counseling minutes. This study combines multiple factors of quitline program use across 2 states to describe how participants use a 5-call program; assess whether intensity of program use is associated with participant subgroups; and assess whether key outcomes (quitting, satisfaction) are associated with intensity. This observational study examines data for quitline participants in Minnesota (n = 2844) and Pennsylvania (n = 14 359) in 2011 and 2012. A subset of participants was surveyed 7 months after registration to assess key outcomes (response rates: Minnesota 65%; Pennsylvania 60%). Quitline utilization data were used to identify program use variables: nicotine replacement therapy provision, number of counseling calls, number of counseling minutes, days from first to last counseling call, and days from registration to first counseling call. Ten program use groups were created using all 5 program use variables, from lowest (1) to highest (10) intensity. Results were similar for both states. Only 11% of Minnesota and 8% of Pennsylvania participants completed all 5 calls. Intensity of quitline program use was associated with several participant characteristics including health conditions and age. Both quit status and program satisfaction were associated with program use intensity. Quit rates peaked in group 9, participants who received the full 5-call program. Quitlines should focus on engaging participants in multiple calls to improve quit outcomes. In addition, it is important to leverage multiple program use factors for a fuller understanding of how quitline participants use a program.


Epidemiology of enuresis among school-age children in Thailand.
Enuresis is a very common developmental problem in young children. The aims of this study were to estimate the prevalence of enuresis in school-age children, to determine the factors associated with nocturnal enuresis, and to evaluate the parental strategies for managing enuresis. A randomly selected cross-sectional population-based study was conducted in eight elementary schools in Bangkok, Thailand. A total of 3453 parents of children aged 5 through 15 years completed the questionnaires. The overall response rate to the questionnaire was 70%. The prevalence of enuresis was 4.2% and that of nocturnal enuresis was 3.9%. The prevalence declined with increasing age from 10%, 5.3%, 3%, and 1.2% at ages 5, 7, 10, and 12 years, respectively. There was no enuretic child at ages 13 through 15 years. The prevalence of bed-wetting was slightly more frequent in females than males. Nocturnal enuresis was also found to be significantly associated with the history of encopresis and positive family history of enuresis. There was no significant associated with parental education, birth order, socioeconomic status, diaper use, toilet training, and behavioral and school problems. Behavioral techniques mostly used by parents for management of their children with bed-wetting were ensuring that the child voids before bedtime (72.9%), waking the child up at night to void (61.8%), and evening water intake restriction (28.5%). The overall prevalence rate of nocturnal enuresis in Bangkok school-age children is lower than that of many previous studies reported from other countries. The significant differences in the prevalence reported by other countries' studies attributed to the criteria selection for ranges of age, definition of enuresis, genetic predisposition, and traditional and cultural background.


A phase Ⅱ, randomized, controlled trial to evaluate the safety and immunogenicity of a Sabin strain-based inactivated polio vaccine.
This phase Ⅱ, randomized, controlled trial aimed to evaluate the safety and immunogenicity of a various Sabin IPV preparations. Six hundred infants aged 60 ~ 90 days received one of five different vaccines: low- (group A), medium- (group B) or high-D antigen content (group C) of an experimental Sabin IPV, control Sabin IPV (group D) or control Salk IPV (group E), on a 0-1-2 month schedule. Participants were observed and followed up within 30 days of each dose to assess safety. Serum samples were collected before the first dose and 30 days after the third dose to assess immunogenicity. After three doses, type-1 seroconversion rates of groups A-E were 99.1%, 100.0%, 99.1%, 99.0%, and 93.4%, respectively; type-2 seroconversion rates were 93.5%, 97.1%, 98.1%, 95.1%, and 91.5%, respectively; and type-3 seroconversion rates were 95.4%, 98.1%, 98.1%, 95.1%, and 100.0%, respectively. Only type-1 seroconversion rates differed significantly for group E. The incidences of injection-site redness (A: 21.9%, B: 23.7%, C: 29.4%, D: 16.2%, E: 12.7%), swelling (A: 6.7%, B: 6.8%, C: 5.0%, D: 0.0%, E: 1.7%) and pain (A: 5.0%, B: 6.8%, C: 7.6%, D: 0.0%, E: 0.9%) all were significantly higher for experimental vaccines relative to control groups. No SAEs were detected related to vaccination, and most adverse reactions were mild or moderate in severity. In conclusion, the experimental Sabin IPVs with low-, medium-, and high-D antigen content all revealed good safety and immunogenicity profiles although being more reactogenic than the control vaccines.