text:
A Plant Vacuolar Protease, VPE, Mediates Virus-Induced Hypersensitive Cell Death
Noriyuki Hatsugai1,2,3,
Miwa Kuroyanagi1,
Kenji Yamada2,3,
Tetsuo Meshi4,
Shinya Tsuda5,
Maki Kondo2,
Mikio Nishimura2,3,
Ikuko Hara-Nishimura1,*
1 Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
2 Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
3 School of Life Science, Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
4 National Institute of Agrobiological Sciences, Tsukuba 305-8602, Japan.
5 National Agricultural Research Center, Tsukuba 305-8666, Japan.
↵* To whom correspondence should be addressed. E-mail: ihnishi{at}gr.bot.kyoto-u.ac.jp
Science 06 Aug 2004:
Vol. 305, Issue 5685, pp. 855-858
Noriyuki Hatsugai
Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan. School of Life Science, Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
Miwa Kuroyanagi
Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
Kenji Yamada
Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan. School of Life Science, Graduate University for Advanced Studies, Okazaki 444-8585, Japan.
Tetsuo Meshi
National Institute of Agrobiological Sciences, Tsukuba 305-8602, Japan.
Shinya Tsuda
National Agricultural Research Center, Tsukuba 305-8666, Japan.
Maki Kondo
Department of Cell Biology, National Institute for Basic Biology, Okazaki 444-8585, Japan.
Mikio Nishimura
Ikuko Hara-Nishimura
For correspondence: ihnishi@gr.bot.kyoto-u.ac.jp
Programmed cell death (PCD) in animals depends on caspase protease activity. Plants also exhibit PCD, for example as a response to pathogens, although a plant caspase remains elusive. Here we show that vacuolar processing enzyme (VPE) is a protease essential for a virus-induced hypersensitive response that involves PCD. VPE deficiency prevented virus-induced hypersensitive cell death in tobacco plants. VPE is structurally unrelated to caspases, although VPE has a caspase-1 activity. Thus, plants have evolved a regulated cellular suicide strategy that, unlike PCD of animals, is mediated by VPE and the cellular vacuole.
Some regulatory mechanisms that underlie programmed cell death (PCD) are thought to be conserved in animals and plants, and many studies have provided evidence that PCD in both shares components that include caspase activity (1–4). However, there is only indirect evidence that caspases are present in plants. The identification of a protease exhibiting caspase activity is essential in elucidating the molecular mechanism that operates PCD in plants. In this study, we have identified VPE (5), a protein that has a proteolytic activity toward a caspase-1 substrate (a caspase-1 activity), as a key component underlying hypersensitive cell death, a typical PCD in plants (6). VPE, like a caspase, is a cysteine protease and was originally found as a processing enzyme responsible for the maturation of seed storage proteins (7, 8). Evidence indicates that VPE is responsible for the maturation or activation not only of various vacuolar proteins in plants (5, 9–11), but also of lysosomal proteins in the mouse (12). Previously, we reported that VPE was up-regulated during cell death in association with leaf senescence and lateral root formation of Arabidopsis (5, 13). This implied that VPE might be involved in plant cell death.
Hypersensitive response (HR) is caused by interactions between plants and incompatible pathogens, in association with rapid and localized cell death (hypersensitive cell death) at the infected sites of host tissues (14). The HR plays a role in preventing the growth and spread of the pathogens into healthy tissues. For this study, we used Nicotiana plants that carried the N resistance gene to tobacco mosaic virus (TMV) to form synchronous lesions that showed hypersensitive cell death in the TMV-infected leaves after a temperature shift (supporting online text and fig. S1). We isolated four VPE cDNAs [NtVPE-1a (DNA Data Bank of Japan, accession no. AB075947), NtVPE-1b (AB075948), NtVPE-2 (AB075949), and NtVPE-3 (AB075950)] from the TMV-infected leaves. Both mRNA and protein levels of VPE were rapidly and transiently increased at an early stage of HR in the leaves (supporting online text and fig. S1). To clarify the effect of VPE on lesion formation, we infected the tobacco leaves with TMV, and then infiltrated each protease inhibitor into the infected region 1 hour before the temperature shift. The characteristic lesion was observed in the TMV-infected region 24 hours after the temperature shift (Fig. 1A). Lesion formation was strongly inhibited by a VPE inhibitor, Ac-ESEN-CHO, and a caspase-1 inhibitor, Ac-YVAD-CHO (Fig. 1A). Other protease inhibitors used were unable to inhibit lesion formation. These results suggest that VPE activity and caspase-1 activity contribute to TMV-induced cell death.
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VPE exhibits a caspase-1 activity involved in hypersensitive cell death. (A) TMV-induced hypersensitive cell death in tobacco leaves is inhibited by a caspase-1 inhibitor and a VPE inhibitor. A TMV-infected tobacco leaf was infiltrated with the indicated protease inhibitors 1 hour before the temperature shift. The photograph was taken 24 hours after the temperate shift. (B) Top: A TMV-infected leaf infiltrated with or without biotin-xVAD-fmk. Bottom: A biotinylated-inhibitor blot of the biotin-xVAD-fmk-infiltrated leaves (lane 1) and control leaves (lane 2). An asterisk indicates nonspecific signals. (C) A biotinylated-inhibitor blot of the TMV-infected leaves that were pre-incubated with each protease inhibitor before further incubation with biotin-xVAD-fmk (lanes 1 to 7) and an immunoblot of the leaf extracts with antibodies to VPE (lane 8). (D) A biotinylated-inhibitor blot of the leaf extract after immunodepletion with antibodies to VPE (lane 1) or with preimmune serum (lane 2). An asterisk indicates nonspecific signals. (E) Effects of various inhibitors on VPE activity in TMV-infected leaves 3 hours after the temperature shift. Each experiment was repeated three times, and vertical bars represent stabdard error. DMSO, dimethylsulfoxide; Ac-YVAD-CHO, a caspase-1 inhibitor; Ac-ESEN-CHO, a VPE inhibitor; Ac-DEVD-CHO, a caspase-3 inhibitor; Pepstatin A, an aspartic protease inhibitor; PMSF, a serine protease inhibitor; E-64, a papain-type-protease inhibitor.
To detect the protein that had caspase-1 activity, we developed a biotinylated-inhibitor blot analysis with an irreversible caspase inhibitor, biotin-xVAD-fmk. In this analysis, an enzyme that conjugates with the inhibitor becomes visible on the blot with streptavidin-conjugated horseradish peroxidase. Like Ac-YVAD-CHO, biotin-xVAD-fmk strongly inhibited lesion formation (Fig. 1B, top). Two bands of 40 and 38 kD were detected specifically on the blot of the extract from the biotin-xVAD-fmk–infiltrated leaves (Fig. 1B, bottom). We examined the competitive effects of various inhibitors on in vitro formation of the enzyme-inhibitor complex with the TMV-infected leaf extracts. When Ac-YVAD-CHO was added as a competitor with biotin-xVAD-fmk, the 40- and 38-kD bands completely disappeared on the blot (Fig. 1C, lane 5). Their signal intensities were reduced with Ac-ESEN-CHO (Fig. 1C, lane 7). On the other hand, the 40- and 38-kD proteins were detected on an immunoblot of the TMV-infected leaves with antibodies to VPE (Fig. 1C, lane 8), which corresponded to the intermediate and mature forms of VPE, respectively (15, 16). The immunodepleted extract from the TMV-infected leaf with antibodies to VPE reduced the signal intensities of both the 40- and 38-kD bands on the in vitro biotinylated-inhibitor blot analysis (Fig. 1D), suggesting that the immunodepletion reduced the level of the active enzyme exhibiting caspase-1 activity. These results imply that the proteases that exhibited the caspase-1 activity in the TMV-infected leaves are both forms of VPE. VPE activity was detected in TMV-infected leaves in vitro (Fig. 1E). Biotin-YVAD-fmk completely inhibited the VPE activity at a concentration of 50 μM and reduced it by 64% at a concentration of 5 μM (Fig. 1E, left). The concentration of the inhibitor was comparable to the concentrations necessary to inhibit the authentic human caspase-1. Other inhibitors had no effect on the VPE activity (Fig. 1E, right). These results imply that the abolishment of lesion formation by the VPE and caspase-1 inhibitors was caused by the inhibition of VPE.
For an in planta analysis, we isolated two VPE homologs of Nicotiana benthamiana [NbVPE-1a (AB181187) and NbVPE-1b (AB181188)], which correspond to the most abundant VPEs in N. tabacum (NtVPE-1a and NtVPE-1b) from the TMV-infected leaves. We used the cDNAs for virus-induced gene silencing (VIGS) with a potato virus X vector (pPVX) to silence VPE genes in N. benthamiana, a species well-suited for VIGS (17). The expression of major VPEs was suppressed in four independent VPE-silenced plants that we generated (supporting online text and fig. S2). We measured the VPE activity on Ac-ESEN-MCA in the VPE-silenced and non-silenced leaves that had been treated with or without salicylic acid (Fig. 2A). VPE activity was reduced in all four independent VPE-silenced plants. These results revealed that the VIGS, which was caused by four independent sequences derived from NbVPEs, abolished both VPE expression and activity, indicating that the specificity to VPE was high in the VIGS. Each circle in Fig. 2A represents the VPE and caspase-1 activities in each of the VPE-silenced and non-silenced plants. The level of VPE activity completely paralleled that of the caspase-1 activity in each plant (Fig. 2A). This result and the immunodepletion analysis of VPE (Fig. 1D) show that VPE is the protease with caspase-1 activity. This was in agreement with our previous result that plant VPEs cleave a peptide bond at the C-terminal sides of not only asparagine residues but also aspartic acid residues (15, 18–20).
VPE deficiency suppresses TMV-induced hypersensitive cell death. (A) Both VPE and caspase-1 activities were measured in the leaves that had been treated with (closed circles) or without (open circles) salicylic acid (SA) for 24 hours, in the VPE-silenced plants (pPVX: VPE, red) and in non-silenced plants including pPVX-inoculated (pPVX, blue) and non-inoculated (no pPVX, green) plants. (B) Non-silenced (pPVX) and VPE-silenced (pPVX: VPE) N. benthamiana plants were infected with TMV on halves of their leaves (indicated by asterisks). The photographs of the plants (left) and the leaves (right) were taken 24 hours after the temperature shift.
To determine how VPE deficiency affects hypersensitive cell death, both the VPE-silenced and non-silenced plants were infected with TMV on different halves of their leaves. The non-silenced plants formed typical visible lesions in the TMV-infected regions of the leaves 24 hours after the temperature shift (Fig. 2B, pPVX, indicated by asterisks). However, the VPE-silenced plants formed no visible lesions in the TMV-infected regions (Fig. 2B, pPVX:VPE, indicated by asterisks). The VPE deficiency suppressed the hypersensitive cell death in response to TMV infection.
It has been shown that disintegration of the vacuolar membranes is the crucial event in plant cell death (21). For an ultrastructural analysis of the VPE-silenced and non-silenced N. benthamiana plants, we examined the TMV-infected leaves 0, 9, and 24 hours after the temperature shift (Fig. 3, A to G). This was because N. benthamiana leaves started to form lesions at 12 hours, which was later than for N. tabacum leaves. The vacuolar membranes were partially disintegrated in the leaves at 9 hours (Fig. 3, C to E), indicating that the disintegration of the vacuolar membranes occurred in the leaves before visible lesions were formed. The disintegration of the vacuolar membranes continued, resulting in complete vacuolar collapse in association with plasmolysis, and finally the cytoplasmic aggregations were left within the cells (Fig. 3B). However, in the VPE-silenced plants, the vacuoles and vacuolar membranes remained intact, even 24 hours after the temperature shift, and no morphological differences except for chloroplasts were found in the leaves before and after the temperature shift (Fig. 3, F and G). Chloroplasts accumulated starch granules in both the silenced and non-silenced leaves at 24 hours (Fig. 3, B and G).
VPE deficiency suppresses vacuolar collapse leading to TMV-induced hypersensitive cell death. (A to G) Morphological changes in the TMV-infected regions of the non-silenced leaves (pPVX) at (A) 0, [(C) to (E)] 9, and (B) 24 hours after the temperature shift, and of the VPE-silenced leaves (pPVX:VPE) at (F) 0 and (G) 24 hours, under the electron microscope. (D) A higher magnification view of the boxed area in (C). Scale bars, 5 μm for (A) to (C), (F), and (G), and 1 μm for (D) and (E). cw, cell wall; pm, plasma membrane; vm, vacuolar membrane; v, vacuole; ch, chloroplast; sg, starch granule. Red triangles indicate the disintegrated parts of vacuolar membranes. (H) The TMV-infected leaves of the non-silenced (pPVX) and VPE-silenced (pPVX:VPE) plants were infiltrated with the vital dye BCECF-AM. Protoplasts were prepared from the leaves at 0 and 9 hours after the temperature shift and then stained with trypan blue. The BCECF fluorescent images (BCECF) and differential interference contrast images after staining with trypan blue (DIC/TB) of the protoplasts were inspected. v, vacuole. (I) Pulsed-field gel electrophoresis of total DNA from TMV-infected leaves of the non-silenced plants at 0 (lane 1), 9 (lane 2), 12 (lane 3), and 24 (lane 4) hours after the temperature shift and of VPE-silenced plants at 24 hours (lane 5).
To investigate vacuolar collapse during hypersensitive cell death, we infiltrated 2′, 7′-bis-(2-carboxyethyl)-5(6)carboxyfluorescein acetoxymethylester (BCECF-AM) into TMV-infected leaves and then prepared protoplasts from the leaves 0, 9, and 12 hours after the temperature shift. We subjected the protoplasts to a diagnosis of vacuolar membrane disintegration with BCECF fluorescence and to a viability assay with trypan blue. Protoplasts that were prepared at 0 hours accumulated BCECF only in the vacuoles (Fig. 3H, pPVX, 0 hours). Protoplasts (n > 100) that were prepared at 9 hours were separated into three staining types (Fig. 3H, pPVX): (I) BCECF-positive and trypan blue–negative (∼70% of the protoplasts), (II) BCECF-negative and trypan blue–negative (∼20%), and (III) BCECF-negative and trypan blue–positive (∼10%). The staining indicates that type I protoplasts were alive and had intact vacuoles. Type II protoplasts were also alive even though the vacuolar membranes had disintegrated (as shown by distribution of BCECF throughout the cell and in the periphery regions inside the cells). Type III protoplasts were dead. At 12 hours after the temperature shift, the number of dead protoplasts in the population was greater (22). The finding that many of the protoplasts with degraded vacuolar membranes were alive suggests that cell death is preceded by vacuolar collapse. All protoplasts from the VPE-silenced leaves were alive and accumulated BCECF in the vacuoles at 9 hours (Fig. 3H, pPVX:VPE) and even at 12 hours (22), which indicates the integrity of the vacuoles in the silenced plants. VPE deficiency suppressed the disintegration of the vacuolar membranes in the TMV-infected leaves. These results suggest that VPE is involved in vacuolar collapse, which triggers hypersensitive cell death.
Plant PCDs are reported to be accompanied by DNA fragmentation (23, 24). Similarly, cleavage of nuclear DNA into ∼50-kb fragments was detected in the TMV-infected leaves at 12 hours after the temperature shift, and the fragmentation was completed at 24 hours (Fig. 3I, pPVX). In contrast, such fragmentation was completely suppressed in the VPE-silenced plants (Fig. 3I, pPVX:VPE). Vacuolar nucleases have been shown to be induced during plant PCD (21). VPE-mediated vacuolar collapse might be involved in the nuclear DNA fragmentation that occurs during hypersensitive cell death.
An immunoblot analysis with antibodies to TMV coat protein (Fig. 4A) showed that the virus was produced more abundantly in the VPE-silenced plants, which formed no visible lesions, than in the non-silenced plants. We densitometrically determined the levels of the coat protein and ribulose-1,5-biphosphate carboxylase-oxygenase (RuBisCO) in three independent experiments (Fig. 4A, bottom). The level of RuBisCO as a loading control was fixed with less than 7% of error. The virus level in the VPE-silenced leaves increased for 24 hours after the temperature shift. In contrast, increase in the virus level in non-silenced leaves was suppressed after 8 hours. The virus level in the VPE-silenced leaves at 24 hours was definitely more than that in non-silenced leaves. Therefore, VPE was involved in suppression of virus production during the HR. On the other hand, induction of pathenogenesis-related (PR) proteins, PR-1 and PR-2, continued after the temperature shift in the VPE-silenced leaves as in the non-silenced plants (Fig. 4B). The VPE deficiency did not affect the production of the PR proteins, although it affected TMV-induced cell death. These results suggest that PCD and defense-protein induction are not coupled during the HR and that the HR is composed of two independent processes, PCD and defense-protein induction. VPE regulates PCD but not defense-protein induction. There has been a lot of discussion about whether PCD during the HR is really critical for resistance (25). Our results suggest that PCD contributes to resistance to a virus infection.
VPE deficiency affects virus proliferation, although it does not affect the production of the PR proteins. (A) An immunoblot showing change in the protein levels of TMV coat protein (CP) in TMV-infected leaves of the non-silenced (pPVX) and VPE-silenced (pPVX:VPE) plants after the temperature shift (top). RuBisCO is a loading control of the immunoblot. The protein levels were densitometrically determined (bottom). Each experiment with a control was repeated with three independent samples, and vertical bars represent standard error. The relative abundance is given as a percentage of the maximum value. (B) Immunoblots showing changes in the protein levels of NbVPE, PR-1, and PR-2 in TMV-infected leaves of the non-silenced (pPVX) and VPE-silenced (pPVX:VPE) plants after the temperature shift.
Although the Arabidopsis genome does not have a caspase family, it has a metacaspase family, which is distantly related to the caspase family. A metacaspase was reported to be involved in the cell death of yeast (26). The gene expression of metacaspase was found in pathogen-infected tomato leaves (27), and a proteolytic activity toward Ac-VEID-MCA (a metacaspase/caspase-6 substrate) was detected in dying suspensor cells of Norway spruce (28). Metacaspases might function in the cytosol during cell death as animal caspases. This is in contrast to the VPE functions in vacuole-mediated cell death. VPE is structurally unrelated to the caspase family, although it has caspase-1 activity and an ability to bind caspase-1 inhibitor.
In animals, dying cells are engulfed by phagocytes. However, in plants, which do not have phagocytes, cells surrounded by rigid cell walls must degrade their materials by themselves. Vacuolar collapse has been shown to trigger degradation of the cytoplasmic structures and lead to cell death (21), although its molecular mechanism is not known. Our findings suggest that VPE functions as a key player in vacuolar collapse–triggered cell death. VPEs are distributed in mono- and dicotyledonous plants. Arabidopsis VPE genes are up-regulated in dying cells during development and senescence of tissues (5, 13). Thus, VPE might regulate various types of PCD in higher plants. Identification of the VPE-target proteins, which are possibly associated with the vacuolar membranes, would help to unravel the molecular mechanism of VPE-mediated vacuolar collapse underlying plant PCD. Because VPE acts as a processing enzyme to activate various vacuolar proteins, it might also convert the inactive hydrolytic enzymes to the active forms, which are involved in the disintegration of vacuoles, to initiate the proteolytic cascade in plant PCD. Understanding the VPE-regulated mechanism, which operates in the early process of the HR, may also lead to practical applications for strengthening disease resistance in crops.
Supporting Online Material
www.sciencemag.org/cgi/content/full/305/5685/855/DC1
SOM Text
Figs. S1 and S2
G. M. Cohen, Biochem. J. 326, 1 (1997).
E. Lam, O. del Pozo, Plant Mol. Biol. 44, 417 (2000).
E. Lam, N. Kato, M. Lawton, Nature 411, 848 (2001).
E. J. Woltering, A. van der Bent, F. A. Hoeberichts, Plant Physiol. 130, 1764 (2002).
I. Hara-Nishimura, M. Maeshima, in Vacuolar Compartments in Plants, A. D. G. Robinson, J. C. Rogers, Eds. (Sheffield, London, 2000), pp. 20–42.
J. T. Greenberg, Annu. Rev. Plant Physiol. Plant Mol. Biol. 48, 525 (1997).
I. Hara-Nishimura, K. Inoue, M. Nishimura, FEBS Lett. 294, 89 (1991).
I. Hara-Nishimura, Y. Takeuchi, M. Nishimura, Plant Cell 5, 1651 (1993).
K. Yamada, T. Shimada, M. Kondo, M. Nishimura, I. Hara-Nishimura, J. Biol. Chem. 274, 2563 (1999).
N. Mitsuhashi et al., Plant Cell 13, 2361 (2001).
T. Shimada et al., J. Biol. Chem. 278, 32292 (2003).
K. Shirahama-Noda et al., J. Biol. Chem. 278, 33194 (2003).
T. Kinoshita, K. Yamada, N. Hiraiwa, M. Nishimura, I. Hara-Nishimura, Plant J. 19, 43 (1999).
R. N. Goodman, A. J. Novacky, The Hypersensitive Response Reaction in Plants to Pathogens: A Resistance Phenomenon (American Phytopathological Society Press, St. Paul, MN, 1994).
N. Hiraiwa, M. Nishimura, I. Hara-Nishimura, FEBS Lett. 447, 213 (1999).
M. Kuroyanagi, M. Nishimura, I. Hara-Nishimura, Plant Cell Physiol. 43, 143 (2002).
S. M. Angell, D. C. Baulcombe, Plant J. 20, 357 (1999).
I. Hara-Nishimura, in Handbook of Proteolytic Enzymes, A. J. Barrett, N. D. Rawlings, J. F. Woessner, Eds. (Academic Press, London, 1998), pp. 746–749.
I. Hara-Nishimura, T. Kinoshita, N. Hiraiwa, M. Nishimura, J. Plant Physiol. 152, 668 (1998).
C. Becker et al., Eur. J. Biochem. 228, 456 (1995).
A. M. Jones, Plant Physiol. 125, 94 (2001).
N. Hatsugai et al., unpublished data.
R. Mittler, L. Simon, E. Lam, J. Cell Sci. 110, 1333 (1997).
A. Levine, R. I. Pennell, M. E. Alvarez, R. Palmer, C. Lamb, Curr. Biol. 6, 427 (1996).
J. T. Greenberg, N. Yao, Cell. Microbiol. 6, 201 (2004).
F. Madeo et al., Mol. Cell 9, 911 (2002).
F. A. Hoeberichts, A. ten Have, E. J. Woltering, Planta 217, 517 (2003).
P. V. Bozhkov et al., Cell Death Differ. 11, 175 (2004).
We thank B. Baker (University of California and USDA–Agriculture Research Service) for donating a binary vector with the TMV resistance gene N, D. C. Baulcombe (John Innes Centre, UK) for donating a Potato virus X vector (pgR107), and T. Kobayashi (National Institute for Basic Biology, Japan) for his help on pulsed-field gel electrophoresis. Supported by Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Corporation, and by Grants-in-Aid for Scientific Research (no. 12138205) and for 21st Century Center of Excellence Research, Kyoto University (A14), from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
You are going to email the following A Plant Vacuolar Protease, VPE, Mediates Virus-Induced Hypersensitive Cell Death
By Noriyuki Hatsugai, Miwa Kuroyanagi, Kenji Yamada, Tetsuo Meshi, Shinya Tsuda, Maki Kondo, Mikio Nishimura, Ikuko Hara-Nishimura
Science 06 Aug 2004 : 855-858


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text:
package liquibase.change.core;

import liquibase.change.AbstractChange;
import liquibase.change.ChangeMetaData;
import liquibase.change.DatabaseChange;
import liquibase.change.DatabaseChangeProperty;
import liquibase.database.Database;
import liquibase.parser.core.ParsedNode;
import liquibase.parser.core.ParsedNodeException;
import liquibase.resource.ResourceAccessor;
import liquibase.sql.Sql;
import liquibase.statement.SqlStatement;
import liquibase.statement.core.RuntimeStatement;
import liquibase.util.StringUtil;

@DatabaseChange(name = "stop", description = "Stops Liquibase execution with a message. Mainly useful for debugging " +
    "and " +
 "stepping through a changelog", priority = ChangeMetaData.PRIORITY_DEFAULT, since = "1.9")
public class StopChange extends AbstractChange {

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        return true;
    }

    @DatabaseChangeProperty(description = "Message to output when execution stops", exampleValue = "What just happened???")
    public String getMessage() {
        return message;
    }

    public void setMessage(String message) {
        this.message = StringUtil.trimToNull(message);
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    public SqlStatement[] generateStatements(Database database) {
        return new SqlStatement[] { new RuntimeStatement() {
            @Override
            public Sql[] generate(Database database) {
                throw new StopChangeException(getMessage());
            }
        }};

    }

    @Override
    public String getConfirmationMessage() {
        return "Changelog Execution Stopped";
    }

    @Override
    public String getSerializedObjectNamespace() {
        return STANDARD_CHANGELOG_NAMESPACE;
    }

    @Override
    protected void customLoadLogic(ParsedNode parsedNode, ResourceAccessor resourceAccessor) throws ParsedNodeException {
        Object value = parsedNode.getValue();
        if ((value != null) && (value instanceof String)) {
            setMessage((String) value);
        }
    }

    public static class StopChangeException extends RuntimeException {
        private static final long serialVersionUID = 6681759443230468424L;

        public StopChangeException(String message) {
            super(message);
        }
    }
}

redpajama_set_name: RedPajamaGithub


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Hi Westmidsgirl, I will have everything crossed for you on Tuesday. I don't think the worry ever goes away, especially when you've been through so much.
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Mark Zuckerberg announced the news to Meta employees Wednesday morning, saying: "I want to take accountability for these decisions and for how we got here.'
according to Meta, the parent company of Facebook, Instagram and WhatsApp.Massive layoffs at Meta Platforms Inc."I know this is tough for everyone, and I'm especially sorry to those impacted.Stock Market Today: Bitcoin Sells Off; Dow Futures Waver Last Updated: Nov 9, 2022 at 8:02 am ET Follow The Wall Street Journal's full markets coverage.
"I want to take accountability for these decisions and for how we got here," Zuckerberg told employees."I know this is tough for everyone, and I'm especially sorry to those impacted.Chief Executive Mark Zuckerberg told employees that he planned to lay off more than 11,000 employees, or about 13% of the company's workforce, according to a post shared to the company's public newsroom Wednesday morning." The layoffs will affect what are known as the company's"Family of Apps" — Facebook, Messenger, Instagram and WhatsApp — and the virtual reality business Reality Labs, Zuckerberg said.House of Representatives on March 25, 2021.They will also affect Meta's business teams, which are being restructured, he said, adding that the company plans to hire fewer people next year and is extending its hiring freeze into the first quarter of next year"with a small number of exceptions.." Zuckerberg said the development follows his decision to"significantly increase our investments" at the start of the pandemic.
He told employees he made that decision based on the belief that e-commerce would continue to grow and provide a strong source of revenue post-pandemic — a prediction that turned out to be wrong, he said.Massive layoffs at Meta Platforms Inc.S."Not only has online commerce returned to prior trends, but the macroeconomic downturn, increased competition and ads signal loss have caused our revenue to be much lower than I'd expected," he said."I got this wrong, and I take responsibility for that.Chief Executive Mark Zuckerberg told employees that he planned to lay off more than 11,000 employees, or about 13% of the company's workforce, according to a post shared to the company's public newsroom Wednesday morning." The job cuts come amid a broader retrenchment in the tech industry that has prompted further layoffs, hiring freezes and other cost-cutting measures across the sector.Please check back for updates.The industry is facing higher interest rates, a stronger dollar that raises costs abroad, and an overall slowing global economy that means less investment in the kinds of speculative projects that tech companies pursue."Not only has online commerce returned to prior trends, but the macroeconomic downturn, increased competition, and ads signal loss have caused our revenue to be much lower than I'd expected," he said.
Oct.28, 2022 06:35 "I think a lot of tech companies held out hope that they'd be able to navigate the softness, but as we've seen during this earnings season, it's going to be a long cold winter for many of these companies as we go through this economic storm," said Dan Ives, managing director and senior equity research analyst at Wedbush Securities." Shares of the Facebook parent company were up about 4% in premarket action.Meta foreshadowed the job cuts in its most recent quarterly earnings statement, saying it would be "making significant changes across the board to operate more efficiently." Those earnings saw its profit slashed by half, causing its stock to fall more than 20%." He gave the example of recruiting, which "will be disproportionately affected since we're planning to hire fewer people next year.Shares are down more than 70% year to date.
"We expect hiring to slow dramatically going forward and to hold headcount roughly flat next year relative to current levels," CFO David Wehner added.Meta, in particular, has felt the sting as it fends off intensifying competition for advertising dollars and users from younger rivals such as TikTok while at the same time contending with new privacy restrictions from long-time nemesis Apple Inc.The latest earnings prompted Morgan Stanley analysts to write in a note to clients that Meta's stock price would be under pressure "until the market can feel confident in execution and return on invested capital from these outsized investments." Zuckerberg said Wednesday that additional measures will be forthcoming at the company, which has approximately 87,000 workers worldwide.Former Meta Chief Financial Officer David Wehner has pegged the hit on potential advertising revenue at more than $10 billion.Employees affected by layoffs in the United States will receive 16 weeks of severance pay plus two additional weeks for every years they've been at the company; payment for their remaining paid time off; six months of health insurance; and immigration support for people on visas, he said.Outside the U." In October, Meta reported its second-ever year-over-year revenue decline while the company's earnings plunged in half, and executives cautioned that they intend for continued spending as they push more deeply into plans for the metaverse.
S., support will be similar, Zuckerberg said, adding that the company will "follow up soon with separate processes that take into account local employment laws."We continue to anticipate that Reality Labs operating losses in 2023 will grow significantly year-over-year," Meta executives said in a filing with the Securities and Exchange Commission that went out Wednesday morning." He said the company removed affected employees' access to most of the company's systems "given the amount of access to sensitive information," but that they would still have access to email throughout Wednesday to "say farewell." Facebook is facing headwinds on multiple fronts, including competition from TikTok, , and a lag in the return on its investment in the Metaverse, a digital universe that remains inaccessible to many.Executives now forecast 2023 expenses of $94 billion to $100 billion, whereas their prior guidance was for $96 billion to $101 billion.Facebook would be the immediate beneficiary of the growing movement to bank TikTok in the U.
S.Meta's hemorrhaging is the latest to whipsaw a tech sector battered by a wave of layoffs and hiring freezes in recent weeks.For now, though, some analysts say TikTok's algorithm is unbeatable when it comes to keeping users on its platform for longer and thus generating more ad revenue."TikTok is simply more fun and engaging than Facebook and Instagram Reels, with Meta far more interested in becoming the platform for the Metaverse than out-innovating TikTok (which was abundantly clear in Zuckerberg's Joe Rogan interview)," analysts with the research group LightShed Partners wrote in a recent note.Lyft Inc.As for the metaverse, Zuckerberg has defended the company's $15 billion bet on the technology."I get that a lot of people might disagree with this investment," he said on the company's earnings call last month.Z , Stripe Inc.
"I think people are going to look back on decades from now and talk about the importance of the work that was done here." Julianne McShane Rob Wile is a breaking business news reporter for NBC News Digital.are among the names that have announced job cuts, while Apple and Amazon.Jonathan Vanian, CNBC.
NBC News »
Facebook parent Meta begins mass layoffs of 11,000 workers as Mark Zuckerberg says 'I take responsibility' Mark Zuckerberg announces Meta will layoff 11,000 employees Meta Stock Price Jumps as Mark Zuckerberg Announces 11,000-Plus Job Cuts Mark Zuckerberg announces Meta will layoff 11,000 employees
Where's the lib outrage? It's almost Christmas ffs! I wonder if it has anything to do with the privacy breach a while back ? getting rid of liability issues
Facebook parent Meta begins mass layoffs of 11,000 workers as Mark Zuckerberg says 'I take responsibility'Massive layoffs at Meta Platforms Inc. began Wednesday, offering a slight boost to the social-media company's beaten-down stock future Gop Not like anyone thought it wasn't your fault Mark.
Mark Zuckerberg announces Meta will layoff 11,000 employeesBREAKING: Mark Zuckerberg announces that Meta will be laying off 11,000 of its employees — an estimated 13% of its workforce — and will also be taking "a number of additional steps to become a leaner and more efficient company." Should there be: Was he afraid if he announced this before the election he would hurt his favoured candidates (party)? Translation: more work for everyone at the same hourly rate.
Meta Stock Price Jumps as Mark Zuckerberg Announces 11,000-Plus Job CutsShares of Facebook parent Meta Platforms rose premarket after founder Mark Zuckerberg said the social-media company would cut more than 11,000 jobs. _**Meta stock was recently up 4.6% at $100. NoMercy Mpedi86 😳 capitalism is wild man. I understand share holders want a payday but damn
Mark Zuckerberg announces Meta will layoff 11,000 employeesMark Zuckerberg has announced that Meta will be laying off 11,000 of its employees -- an estimated 13% of its workforce.
Facebook parent Meta cuts 11,000 jobs, 13% of workforceFacebook parent Meta is laying off 13% of its employees as it contends with faltering revenue and broader tech industry woes.
Facebook Parent Meta Trims 13% of Workforce, Citing Lack of Post-Pandemic Growth"I got this wrong, and I take responsibility for that," Mark Zuckerberg writes in a memo to staff announcing a reduction of 11,000 employees. About Facebook. It's sad when you need help with your Facebook account and there's no one there to help you out. When you send for a code and you never get one. They need to hire more people to assist with the problem instead of laying off people.
09 November 2022, Wednesday News
Democrats Cling to Supermajorities in N.Y. Legislature Amid G.O.P. Gains
Shots fired after police pull over car in Brooklyn

redpajama_set_name: RedPajamaCommonCrawl


From time to time (in between our packed order book) we have bodies and necks available for purchasing. These are mainly alder and ash made from one or two pieces and typically won't be full finished. You'll be able to see them before they have been wet sanded, buffed and aged.
SOLD – Shoreline gold S Type made from one piece swamp ash. Approximate weight is 3 1/2lbs unloaded. The clear coat has been vintage tinted and we will continue to age it once the lacquer has hardened. The buyer can specify the level of ageing the body gets. We are offering this body at a special price of £300 unloaded plus £20 shipping. A deposit of £80 is required and the final balance is payable upon completion. Our estimated date for delivery is Feb 18th-24th.
SOLD – 3 tone burst S Type made from 3 piece swamp ash. Approximate weight is 4lbs unloaded. The clear coat has been vintage tinted and we will continue to age it once the lacquer has hardened. The buyer can specify the level of ageing the body gets. We are offering this body at a price of just £270 unloaded plus £20 shipping. A deposit of £80 is required and the final balance is payable upon completion. Our estimated date for delivery is Feb 25th-28th.
For sale – Alder 2 piece S Type body finished in a stunning early 60s inspired burst. We have finished the body in a our vintage clear coat which has given the lacquer a healthy gloss and Amber/yellowed tint. Approximate weight unloaded is 4lb and will be ready for shipping between April 1st and 5th. £290 plus shipping, a deposit of £80 holds it. Remaining balance to be paid upon completion.


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Tom Brands expects to see the real Alex Marinelli on Sunday
IOWA WRESTLING
STEVE BATTERSON Quad-City Time
Marinelli
IOWA CITY – Tom Brands expects "the real'' Alex Marinelli to surface Sunday when the Iowa wrestling team is tested for the first time as the nation's top-ranked team.
"We haven't seen that guy yet, but I have a feeling we will. He'll be ready to go,'' the Hawkeye coach said.
Iowa's second-ranked 165-pouhd junior will be featured during the Hawkeyes' 7 p.m. Big Ten opener against sixth-ranked Wisconsin, facing the Badgers' third-ranked Evan Wick.
Marinelli will also be featured following tonight's televised meet at Carver-Hawkeye Arena, the subject of a BTN documentary that will debut at 9 p.m.
In an episode of The B1G Story, Marinelli's friendship and bond with former Wisconsin wrestler Eli Stickley is at core of the documentary.
It reflects on the friendship the pair had and how following Stickley's death in a July, 2018 auto accident the Iowa wrestler works to honor and the keep alive the memory of his friend.
Brands said the Hawkeyes' dual with the Badgers was moved to the unique Sunday evening time slot so it could be paired up with the BTN feature.
"He has a good story to share,'' Brands said. "We're fine with wrestling them now, that's fine.''
Iowa moved into the top spot in the national polls last week after Arizona State ended Penn State's 60-dual win streak.
Brands expects that to only add to the match-up between the Hawkeyes (2-0) and Badgers (6-0).
"They're saying they are coming to Iowa City loaded for bear and they're excited,'' Brands said. "We've got to get ready to go.''
That includes Marinelli, who Brands believes has wrestled to the level of his competition in winning his first two matches of the season.
"When Alex Marinelli is at his best, he's moving his feet, moving his hands and has the ability to score a lot of points,'' Brands said. "We haven't seen that guy yet, but I think we'll see him gear up for a big match. I think he'll be ready.''
Marinelli has won his last three matches against Wick, most recently taking a 2-1 decision in the semifinals of last season's Big Ten Championships.
He understands that he will need to take his work to a higher level than he has in his two season-opening wins.
"I think I can do better,'' said Marinelli, who has a 17-0 career record in Big Ten duals. "I need to come out and really be ready to go, dominate. I think I can score a lot more points than I have.''
Marinelli won't be the only Hawkeye facing an early-season challenge.
Iowa's second-ranked Austin DeSanto is expected to face top-ranked Seth Gross at 133 and Hawkeye freshman Tony Cassioppi faces second-ranked Wisconsin sophomore Trent Hilger at 285. Both Badgers bring 6-0 records into the dual.
"I'm not going to approach it any differently than I would any other match,'' Cassioppi said. "I always focus on myself, make sure that my feet and hands are where they need to be and make sure that I'm ready to go.''
DeSanto finished 6-5 a year ago in matches against top-10 opponents, his highest-ranked win coming against third-ranked Nick Suriano of Rutgers in a January dual.
Cassioppi, ranked 12th, will be facing a top-five opponent for the first time in his career and Brands sees his approach focused on wrestling his match as a prudent one.
"Every time out is big for our guys,'' he said. "Rankings, seedings, all those things that are important in March, these matches matter. More than ever before, the committee is not inserting itself into things as much. It's based more and more on a formula and results. We've got to be up to the challenge.''
College-sports
Tom Brands
Alex Marinelli
SPORTS BRIEFS: Kingsley's Nick Phelps to walk-on at Iowa
Kingsley's Phelps to walk-on at Iowa
SPORTS BRIEFS: Bishop Heelan baseball coach Andy Osborne to help out Briar Cliff
SIOUX CITY -- Briar Cliff head baseball coach Corby McGlauflin has named Andy Osborne to the assistant coaching position with the Chargers.
Nebraska offensive coordinator Troy Walters leaves football program
LINCOLN, Neb. -- Nebraska will have a revamped coaching staff in 2020.
USD women hand South Dakota State its worst Summit League loss ever
The 35-point victory for USD stands out even more considering in the previous 16 contests since the Coyotes joined the Summit League, the average margin of victory between the two schools was eight points.
COLLEGE BASKETBALL ROUNDUP: Jamie Sale wins 500th game with Morningside
SIOUX CITY — Morningside College women's basketball coach Jamie Sale earned his 500th win with the program Wednesday, as the seventh-ranked Mu…
UNI makes road statement over Bradley
PEORIA, Ill. -- Protect a road lead with first place on the line.
Iowa wrestling gains optimism heading into Saturday's dual against Nebraska
IOWA CITY, Iowa -- Entering the heart of its dual schedule, the Iowa wrestling team senses the possibilities.
Tuesday starts 2020 Iowa football season
IOWA CITY, Iowa – Tuesday is more than the start of spring semester classes at Iowa.
No. 1 Morningside men pull away late against Dordt
SIOUX CENTER, Iowa – The Dordt men's basketball team gave top-ranked Morningside all it could handle on Saturday.
No. 3 Concordia builds 18-0 start to complete season sweep of Briar Cliff
There was a glimmer of hope for the Briar Cliff women's basketball team on Saturday against Concordia, but the third-ranked Concordia Bulldogs put any hope to rest in the second quarter.
PHOTOS: Briar Cliff hosts Concordia
PHOTOS: Snow blankets Sioux City
Way-too-early 2020 college football top 25 rankings
Photos: See all the highlights of college football's championship game
Tiger vs Tiger: Photos to get you ready for the NCAA National Championship game


text:
Sony BMG Will Allow Amazon to Sell Its Music Without DRM
Sony BMG made history Thursday by becoming the fourth and final major label to allow its music to be sold without digital rights management, issuing a announcement that Amazon.com's MP3 store would start carrying music from the label by the end of this month. This day has been a long time coming. After consumers are […]
Sony BMG made history Thursday by becoming the fourth and final major label to allow its music to be sold without digital rights management, issuing a announcement that Amazon.com's MP3 store would start carrying music from the label by the end of this month.
This day has been a long time coming. After consumers are able to buy music that plays on a wide variety of equipment, analysts expect the market for digital music and associated devices to expand.
"We are excited to be working with Amazon as they continue to build newmarkets for digital music," said Thomas Hesse, president of Sony BMG's global digital business and US sales unit. "We are constantly exploring new ways of making our music available toconsumers in the physical space, over the internet and through mobilephones, and this initiative is the newest element of our ongoingcampaign to bring our music to fans wherever they happen to be."
Like the rest of the music available on Amazon MP3, Sony BMG's fileswill be available in a 256 Kbps MP3 format for $0.89 or $0.99, or$6 to $10 per album (in most cases).
This is great news for music fans and opponents of DRM. There is also, however, the question of watermarks.
Representatives for both Sony BMG and Amazon confirmed that the files will in factcontain watermarks. However, privacy advocates needn't be alarmed – the reps also told me that the only information to be included inthe watermarks is where they were purchased. Inother words, if you mistakenly share the files over the internet, theywill not be traceable to you, only to Amazon.
Despite Move to MP3s, DRM Will Haunt Record Labels
Death of DRM Could Weaken iTunes, Boost iPod
Report: RIP DRM, as Last Major Label Plans to Ditch Restrictions
Like Amazon's DRM-Free Music Downloads? Thank Apple
TopicsdrmListening Post
Ice Cream Machine Hackers Sue McDonald's for $900 Million
Kytch alleges that the Golden Arches crushed its business—and left soft serve customers out in the cold.
The Spectacular Collapse of Putin's Disinformation Machinery
A few critical errors have brought down Russia's complex and objectively brilliant war of influence in the West.
Tom Southern
Russia Is Leaking Data Like a Sieve
Ukraine claims to have doxed Russian troops and spies, while hacktivists are regularly leaking private information from Russian organizations.
Matt Burgess
How to (Ethically) Get Rid of Your Unwanted Stuff
With so many extensive online selling and donation resources, there's no need to get bogged down.
Jaime Stathis


Templeton Insurance Agency is a family owned Independent Insurance Agency. Our agency was founded in 1986 by myself, Dr. Randall (Randy) K. Templeton, CPIA, LUTCF, EIS, CMA, MBA, DBA. My wife, Kay Templeton, CIC, CISR, joined me in the agency in 1990. We both continue to operate the agency with a hands on approach, working daily to meet our client's needs.
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Disclexington Productions originated as the record producing arm of the Houston-based underground rock group, de Schmog. The name Lexington comes from the street where the band practiced. The residential street butted up to a freeway and so the rent was cheap. This brought bands, artists and other bohemians to Lexington and for several years there was a great community spirit of creativity. Disclexington is now based on Chicago's Southside in the Heart of Chicago neighborhood.
Disclexington has recently released Ed, an eight- band compilation that includes the music of Bob Taylor, Brillo, Broadtosser, churchbus, Hotel Brotherhood, New Town Drunks (from Chapel Hill, NC), the C*nts, and Urban Djin (see my interview with Urban in the archives). This poignant and engaging compilation firmly indicates that Disclexington Productions has a promising and important future. In fact, this year Disclexington plans to release new albums by churchbus, New Town Drunks, THE LATEST and Bright Men of Learning, as well as re-release some work of de Schmog, including the rock opera de Schmog Fairy Tale. Visit Kilian Sweeney's label at disclexington.com to listen to samples and to purchase Ed.
Q: To put out a compilation as a first release seems to me to work as a statement: this is the framework within which this label will draw and hone its inspiration. When initially soliciting participation from such a wide cast of talent, did you suspect that they would flow together? Or has the flow of Ed come as a surprise?
Sweeney: I hope it flows. As the producer I am too biased to tell, but I am always looking for flow and continuity in life. Yes, I think it flows amazingly.
The project came together in stages. It is 8 bucks for eight bands recorded on an 8-Track (not one of those old stereo 8-tracks but a half-inch analog tape machine). The 8-Track machine was sort of a gift from Ed Skinny Horse who had some kind of personal revelation, and up and moved to Cambodia. He gave Snake all his gear and we decided it had to be put to use. We got an 8-Track expert to help show us how to use the darn thing. That was Kris Poulin, a terrific engineer who has worked on lots of great Chicago projects including Devin Davis' Lonely People of the World Unite. He also plays in the band Love Story in Blood Red. Anyway, we started recording our band churchbus, but I thought that to get really intimate with the gear we had to record some other bands — you know, meet some new challenges. So it just appeared to be clever to do eight bands. Somewhere along the way, after recording three bands and hearing how good it was, I decided I should release it.
It is not actually the first Disclexington release, but it is the first in probably 12 years and before Disclexington was based in Houston. Now I'm in Chicago's Heart of Italy neighborhood on the South Side. About 15 years ago Disclexington put out an album called Ed, which was named after a guy in Houston who was really generous to my band at the time. So the name of this album and the reason for the name is sort of an inside joke for me that I'm sharing with you. It also speaks to the idea of "what comes around goes around" like the way the actual image of the number eight does: 8. Ed-Ed. Also it is the way the reel of tape looks while on an 8-track machine... I could go on and on.
Q: Compilations always remind me of the cinema, and Disclexington's is no different. In my imagination there's a movie described by Ed (a bit sideways, but not without a cool pathos — a sort of Trees Lounge, but only set in Canaryville with Buscemi's character being a failed crossword puzzle constructor rather than an unemployed mechanic, and with a different name: "Trunks Saloon.") Can you describe the "movie" that's showing in your head when you're listening to Ed?
Sweeney: I'd like to think it is a movie about Ed Skinny Horse. His life seems really interesting to me. But he might not like it. In fact, I think he is a little embarrassed by this whole thing as it is.
This question reminds me of how the cover art came about. I asked Kathleen Judge to do the cover art for this record because she is a terrific local artist who actually knows Ed and most of the local bands on this record. When I ask an artist to do work I don't like to give them ideas because I respect their creativity. But in this case I did throw an idea at her. I told her that none of us really knows what Ed is doing in Cambodia and we haven't seen any pictures, so maybe she could imagine what Ed is doing, like in a voyeuristic way. Well, thankfully she didn't listen to me and came up with something really special on her own. She's great. She's done terrific work for Oscar Brown Jr., Neko Case and many others, so I'm so honored to have her work on the cover. She also has two pieces up at the Chicago History Museum right now. I just feel honored. I know I got off course there, but what the hell.
Q: I've known actors who despise hanging out with other actors; writers and poets who would rather slash their eyeballs with a razor blade than attend a reading. I've even known a few artists who... well, they are very lonely people today. But I have yet to meet a songwriter who does not genuinely enjoy the company of fellow songwriters (I'm opposing songwriters to musicians here). What do you think it is that binds songwriters so strongly?
Sweeney: I don't know if that's entirely true. But maybe songwriters are a bit more extroverted than writers and poets and that ilk just by the fact that they often go for the immediate thrill of public affection. Bands can be really competitive. That's actually one of the reasons I wanted to put this out, sort of get a community feel for the project. It is something the South Side could be proud of because a lot of these artists are from the South Side, or have ties to the South Side, and in fact it was recorded over by there.


text:
Germany, Turkey
Since his parents died, the teenager Burak lives with his grandmother and his uncle, Cemil, in a small village in Turkey. They make a living selling pomegranates —but, while Cemil is happy with a simple life, Burak wants to move to a big city and study in college. When the grandmother gets sick, the two men need to make tough decisions.
Germany Turkey female directors family drama maturing religion social portrait youth
Sevgi Hirschhäuser
Sevgi is a director, screenwriter and editor. She lives in Munich, Germany, and has worked in different film departments: she started as an editor and, later, began to write scripts. Toprak is her debut as a feature film director.


text:
Archived content. See ABS Website for latest information and statistics
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1301.0 - Year Book Australia, 2006
ARCHIVED ISSUE Released at 11:30 AM (CANBERRA TIME) 20/01/2006
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About this Release
Australian Deserts, Introduction (Feature Article)
Australian Deserts, Climatic aspects of Australia's deserts (Feature Article)
Australian Deserts, Deserts past - the archaeology and environmental history of the Australian deserts (Feature Article)
Australian Deserts, Desert wildlife of Australia (Feature Article)
Assisting countries combat desertification - Australia's role (Feature Article)
Ageing Australians (Feature Article)
Urban and non-urban population (Feature Article)
Recent fertility trends (Feature Article)
Future living arrangements (Feature Article)
People who work few hours (Feature Article)
Casual employees (Feature Article)
Labour force status of migrants (Feature Article)
Older people with disabilities (Feature Article)
Labour force characteristics of people with a disability (Feature Article)
Children's injuries (Feature Article)
School students' mathematics and science literacy (Feature Article)
Likelihood of victims reporting crime to police (Feature Article)
The Australian wheat industry (Feature Article)
Kangaroo bonds (Feature Article)
2006 Year Book Australia released today (Media Release)
Contents >> Chapter 5 - Population >> Population size and growth
POPULATION SIZE AND GROWTH
Australia's estimated resident population at June 2004 was just over 20.1 million, an increase of 1.2% over the previous year (table 5.1). This figure has increased by 12% over the past decade. Australia's growth rate of 1.2% for the 12 months to June 2004 was the same as the overall world growth rate (table 5.2).
5.1 COMPONENTS OF POPULATION CHANGE AND ESTIMATED RESIDENT POPULATION(a)
Components of population change
Births(b)
Deaths(b)
increase(b)
Net overseas migration(c)
At end of
Increase(d)
Year ended 30 June
(a) Includes Other Territories.
(b) Numbers of births and deaths are on year of occurrence basis and differ from those shown in the births and deaths section of this chapter.
(c) Includes migration adjustments from June 2001.
(d) The difference between total growth and the sum of natural increase and net overseas migration during 1999-2001 is due to intercensal discrepancy.
Source: Australian Demographic Statistics (3101.0).
When compared with other countries, Australia's population growth rate was similar to New Zealand (1.1%); higher than Canada (0.9%), the United States of America (0.9%), and Hong Kong (0.7%); considerably higher than the United Kingdom (0.3%), Japan (0.1%) and Germany (0.0%); and well below the growth rates for Papua New Guinea (2.4%) and Malaysia (1.9%). China (0.6%), ranked as the largest population, had a growth rate half that of Australia.
Figures provided by the US Census Bureau's International Data Base for 227 countries rank Australia's population 52nd in size for the year 2004 and project a fall to 64th position by 2050.
5.2 POPULATION, GROWTH RATE AND RANK, Selected countries
Estimated population
Projected population
Source: Australian Demographic Statistics (3101.0); US Census Bureau, 'International Data Base', viewed 21/07/05, <http://www.census.gov>.
Australia's estimated resident population of 20.1 million at 30 June 2004 has grown by nearly 2.2 million persons during the past decade. The growth of Australia's population has two components: natural increase (the number of births minus the number of deaths) and net overseas migration (net permanent and long-term migration). For state and territory estimates, a third component - net interstate migration - is also included. Since Federation in 1901, Australia's population has increased by 16.4 million persons. Graph 5.3 shows the growth in Australia's population since European settlement in 1788.
Table 5.4 shows that population growth has not occurred evenly across the states and territories. The proportion of Australia's population resident in each state and territory has changed over time. From 1954 to 2004 the proportion of the Australian population living within New South Wales, the most populous state, decreased (from 38% to 33%), as did Victoria (from 27% to 25%), South Australia (9% to 8%) and Tasmania (3% to 2%). All other states and territories show an increase over this same time. The proportion of Australia's population living in Queensland increased from 15% in 1954 to 19% in 2004. Likewise, during the same period Western Australia experienced an increase from 7% to 10%, the Australian Capital Territory from less than 1% to 2% and the Northern Territory from less than 1% in 1954 to 1% in 2004. Western Australia became the fourth most populous state in 1983, overtaking South Australia.
5.4 POPULATION, By states and territories
Vic.
Tas.
Aust.(a)
(a) Includes Other Territories from 1997. Prior to 1997 Jervis Bay territory was included with the ACT, and Christmas and Cocos (Keeling) Islands were excluded from population estimates for Australia.
Source: Australian Demographic Statistics (3101.0); Australian Historical Population Statistics (3105.0.65.001).
COMPONENTS OF POPULATION GROWTH
Over the last 50 years the population has more than doubled from a resident population of 9 million in 1954 to over 20 million in 2004. Natural increase has been the main component of population growth in Australia over the past 50 years, contributing around two-thirds of the total increase. Net overseas migration, while a significant source of growth, is more volatile, fluctuating under the influence of government policy as well as political, economic and social conditions in Australia and the rest of the world.
The yearly growth rates due to natural increase and net overseas migration from 1954 to 2004 are shown in graph 5.5.
Fifty years ago, Australia was in the midst of a baby boom. In 1954 the rate of natural increase was 13.4 persons per 1,000 population, peaking at 14.3 in 1961. After 1962, declining fertility led to a fall in the rate of natural increase. The rate of natural increase rose in the late-1960s, reaching a peak of 13.1 persons per 1,000 population in 1971; a decade later it had fallen to 8.6. In 1996 the rate of natural increase fell below 7.0 for the first time in Australia's history. This downward trend continued, reaching 6.1 persons per 1,000 population in 2004. ABS population projections suggest that continued low fertility, combined with an increase in deaths due to an ageing population, would result in natural increase falling below zero sometime in the mid-2030s.
In 2004 the crude death rate was 6.6 deaths per 1,000 population, falling from 9.1 in 1954. The crude birth rate has declined from 22.5 births per 1,000 population recorded in 1954 to 12.7 in 2004. The lowest ever birth rate, just over 12.6 births per 1,000 population, was recorded in 2003. Crude birth and death rates from 1954 to 2004 are shown in graph 5.6.
POPULATION AGE AND SEX STRUCTURE
Over the last 50 years the absolute number of persons has increased in all age groups. However, the proportion of the total population in older age groups has increased while the proportion in younger age groups has declined. Graph 5.7 shows the proportions of the population by age group and sex in 1954 and 2004, illustrating the ageing of Australia's population. Australia's population is ageing because of sustained low fertility - which has resulted in proportionally fewer children in the population - and increased life expectancy.
5.7 AGE DISTRIBUTION OF POPULATION - 1954 and 2004
(a) The 85+ age group includes all ages 85 years and over and is not directly comparable with the other 5-year age groups.
Source: Australian Historical Population Statistics (3105.0.65.001); Population by Age and Sex, Australian States and Territories (3201.0).
In 1954 there were 105,700 more males than females in Australia's population, while in 2004 there were 122,200 more females than males. Since 1979 Australia has been home to more females than males.
In 1954, people under 15 years of age represented 28.6% of Australia's population. Those aged 15-64 years represented 63% and those aged 65 years and over represented 8%. Although Australia's population has continued to grow since 1954, the proportion of people aged 15-64 years increased to 67% in 2004. During this period the proportion of children 0-14 years decreased to 20%, although their absolute numbers increased, while the proportion of the population aged 65 years or more increased to 13% (graph 5.8).
The median age of the Australian population (the age at which half the population is older and half is younger) has increased by 5.9 years in the last 20 years from 30.5 years in 1984 to 36.4 years in 2004. Graph 5.9 shows the median ages of the population for the states and territories in 1984 and 2004.
In 2004 the population of South Australia had the highest median age of all states and territories (38.5 years) followed by Tasmania (38.4 years) and New South Wales (36.6 years). The Northern Territory (30.6 years) had the lowest median age.
Tasmania experienced the largest increase in median age over the 20 years to 2004, increasing by 8.5 years from 29.9 years in 1984 to 38.4 years in 2004. The next largest increase was South Australia at 7.1 years, increasing from 31.4 years in 1984 to 38.5 years in 2004.
There were just over 2.6 million people (13% of the total population) in Australia aged 65 years or more in June 2004, an increase of 58,500 people (2%) from June 2003 with all states and territories experiencing growth in this age group. The Northern Territory (6%), the Australian Capital Territory (3%) and Western Australia (3%) experienced the greatest increase in persons aged 65 years or more.
5.10 POPULATION AGED 65 YEARS AND OVER, Proportion and growth
Proportion of population in 2004
Growth of population between 2003 and 2004
Australia(a)
Source: Population by Age and Sex, Australian States and Territories (3201.0).
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Indian Springs boys soccer scores late, beats…
SportsHigh School Sports
Indian Springs boys soccer scores late, beats Jurupa Hills, 1-0
Indian Springs celebrates a goal against Jurupa Hills late in the second half at Indian Springs High School in San Bernardino, CA., Friday, January 13, 2017. Indian Springs defeated Jurupa Hills 1-0. (Staff photo by Jennifer Cappuccio Maher/The Sun/SCNG)
By Pete Marshall | pmarshall@scng.com | Daily Bulletin
January 13, 2017 at 10:45 p.m.
SAN BERNARDINO >> It wasn't the ideal conditions for the undefeated Indian Springs boys soccer team.
The Coyotes were not only missing their coach, John Arient, due to a red card he was given in their last match, but they were having to play on an alternate field at Indian Springs after a drainage hole opened up on the stadium field due to recent rains.
And to top it all off, Jurupa Hills was giving Indian Springs all it could handle.
Until finally, in the 78th minute, Juan Aparicio scored the goal that lifted the Coyotes to a 1-0 victory over the Spartans in a San Andreas League game.
Indian Springs, ranked No. 2 in the latest CIF Southern Section Division 5 poll, improved to 14-0-2, 2-0. Jurupa Hills dropped to 5-4-3, 0-1-1.
"We didn't play our normal game," said acting coach Rosa Esparza, who is usually the team's assistant coach. "I'm not sure if it was because their coach wasn't here. But at least we got the win."
For the game-winner, Aparicio applied pressure, stealing the ball away from the Spartans defense with the goalie out to challenge Aparicio. His first shot, with his right foot, hit off a defender. The rebound went to his left foot and he scored.
Outside of the game-winner, Esparza thought there was a lack of aggression at times. The game was played on a field in the northeast portion of campus, where Jurupa Hills was attacking downhill in the first half and Indian Springs was downhill in the second half. The grass wasn't as consistent as a normal field.
"That's not an excuse," Esparza said. "We play games in the stadium, but we practice on this field."
But ultimately, it was Jurupa Hills that was left more disappointed. The Spartans were wary of Indian Springs and its high-scoring attack.
"We weren't trying to be too aggressive," Jurupa Hills coach Armando Fresquez said. "We gave them possession in their own end. We didn't want to get caught. At the end, we would've been happy with 0-0."
In standing with Jurupa Hills' strategy, the Spartans had some chances on offense, but there wasn't a sustained pressure like Indian Springs had. In the 58th minute, Jose Hernandez's corner kick first went to Danny Godinez, whose shot ricocheted off a defender. He eventually got the rebound, but his shot slid wide.
"We have a tie and a loss (in league)," Fresquez said. "We just need to go out and get a win."
Pete Marshall | reporter
Pete Marshall started his career as a freelancer for The Sun in 1991, then later was hired full time by the Inland Valley Daily Bulletin in 1995. Since then he has covered a variety of sports for the Daily Bulletin and The Sun, primarily high school sports and minor league baseball. He's been doing it long enough that he's now covering the children of student-athletes he covered when he first started.
pmarshall@scng.com
Follow Pete Marshall @PeteMarshallLaw


Toy sewing machine - Linnea.
Attributed to the manufacturers Bergbom & Roberg, the Linnea was made in Chicago, USA. Production has been suggested as 1920s, but new information indicates an earlier, turn of the century date.
The model appeared under the guise of various names including 'Englewood Junior'.


Idube is a safari lodge situated in the Sabi Sand Game Reserve, in the heart of South Africa's premier wildlife conservation area of the Greater Kruger Park. Game, including the Big 5, is viewed really close by from open Landrovers, or spotted on guided walks. All our experienced rangers and trackers are trained to give guest the best possible wild life experience.
This three-star Lodge with its thatched chalets and en-suite bathrooms ensure that Isiyala's guests feel pampered and relaxed.
This magnificent reserve is 12 000 acres large consisting of savannah, bush veld and riverine areas, with hills and gorges, mountains and valleys.


text:
Efficacy of mometasone furoate nasal spray in the treatment of acute rhinosinusitis
Sandeep Shrestha ORCID: orcid.org/0000-0001-9845-07601,
Rupesh Raj Joshi2 &
Swikriti Shrestha3
The Egyptian Journal of Otolaryngology volume 39, Article number: 14 (2023) Cite this article
Acute rhinosinusitis (ARS) refers to a group of disorders characterized by inflammation of the respiratory epithelium of the nose and paranasal sinuses lasting from 7 to 28 days. In the treatment of ARS in addition to an antibiotic, intranasal corticosteroids hasten the clearance of bacteria, decrease the frequency and severity of disease recurrence, and reduce the duration of infection. The purpose is to compare the efficacy of the combination of mometasone furoate nasal spray (MFNS) with amoxicillin and amoxicillin alone in the treatment of acute rhinosinusitis. A total of 120 patients (≥ 12 years) were randomized into 2 groups: group A (N: 60) receiving amoxicillin 500 mg thrice daily alone and group B (N: 60) receiving amoxicillin 500 mg thrice daily and MFNS 200 μg twice daily for 7 days. Patients were followed up after 7 days. The Sino-Nasal Outcome Test-22 (SNOT-22) questionnaire was taken before and after. The total score of SNOT-22 was compared between the groups.
There was a reduction in the mean total SNOT score in both groups from 21.32 ± 11.29 to 9.37 ± 6.55 in group A and from 26.68 ± 11.97 to 3.07 ± 3.46 in group B which were statistically significant (p < 0.001) in both groups. The posttreatment mean score with the amoxicillin group was 9.31 ± 6.55 and that of the amoxicillin and mometasone furoate group was 3.07 ± 3.46, and their mean difference was 6.3 ± 0.95. In comparison, MFNS with amoxicillin was significantly (p < 0.001) superior than amoxicillin alone.
Patients receiving amoxicillin alone or amoxillin with MFNS, both showed improvement of symptoms in ARS. However, amoxicillin with MFNS showed significantly higher improvement and relief of symptoms in ARS than amoxicillin alone.
Rhinosinusitis refers to a group of disorders characterized by inflammation of the ciliated respiratory mucosa of the nose and paranasal sinuses (PNS) [1].
The term rhinosinusitis is replaced by "sinusitis" as the inflammation of the sinus cavities is almost always accompanied by inflammation of the nasal cavities. Rhinitis is inflammation of the mucosa of the nasal cavity whereas sinusitis is inflammation of the mucosa of the paranasal sinuses [2, 3].
Most acute rhinosinusitis (ARS) begins when a viral upper respiratory infection (URI) extends into the paranasal sinuses, which may be followed by bacterial infection [4]. Both viruses and pathogenic bacteria have been shown to be involved in the pathogenesis of ARS [5,6,7]. It is theorized that most cases of ARS are first caused by a virus and then in some cases are complicated by bacterial co-infection or secondary infection [4, 8]. Inflammation of the mucosa of the sinus can lead to obstruction of the sinus ostia, retention of secretions, and bacterial invasion. The obstruction, mucus retention, and infection produce the signs and symptoms characteristic of rhinosinusitis [9].
Prevalence rate of ARS is 6–15% and is usually a self-limiting disease, but serious complications leading to life-threatening situations and even death have been described [10]. It is one of the most common reasons for the prescription of antibiotics, and proper management is extremely pertinent in the context of the global crisis of resistance to antibiotics [10].
In the treatment of acute bacterial rhinosinusitis in addition to antibiotic, intranasal corticosteroids hasten the clearance of bacteria, decrease the frequency and severity of disease recurrence, and reduce the duration of infection [11,12,13,14]. Mometasone furoate (MF) is a potent, topically active, synthetic corticosteroid, which has been formulated as a nasal spray and was approved for the treatment of seasonal and perennial allergic rhinitis [9].
Sino-Nasal Outcome Test-22 (SNOT-22) was developed in 2009 from modification of SNOT-20 with the addition of nasal blockage and loss of smell, by the National Comparative Audit of Surgery for Nasal Polyposis and Rhinosinusitis Royal College of Surgeons of England [15, 16]. It has been validated and is today one of the most frequently used survey instruments in sinonasal research. It measures rhinosinusitis health status and quality of life and will be used in this study for the assessment of improvement in patients. Lower scores imply a better health-related quality of life, and the theoretical range of the score is 0 to 110 [15, 16].
Aims and objective
• To assess the efficacy of mometasone furoate nasal spray in the treatment of acute rhinosinusitis
• Patients aged 12 or more years with signs and symptoms of acute rhinosinusitis for more than 7 days but less than 28 attending ear, nose, and throat (ENT) OPD, NMCTH
• Patients who give consent
• Less than 12 years
• Patient with chronic rhinosinusitis (or sinus or nasal surgery for this condition within 6 months before screening)
• Atrophic rhinitis and nasal polyps
• An allergy to corticosteroids or any other condition that would interfere with study evaluations
• An allergy to amoxicillin
• Patients who do not give consent
This study was conducted on patients aged 12 years and above who presented to the Otorhinolaryngology OPD of NMCTH, Attarkhel, Kathmandu, within a period from October 2018 to March 2020. This study was a single-blinded randomized controlled trial. In this study, patients and patient's party did not know in which treatment group they were included.
Patients presenting with symptoms of ARS and fulfilling the criteria as per the Rhinosinusitis Task Force of the American Academy of Otolaryngology-Head and Neck Surgery (i.e., 2 major or 1 major with 2 minor symptoms) were divided randomly through a computerized lottery system into groups A and group B, where group A was treated with amoxicillin 500 mg thrice daily for 7 days and group B with amoxicillin 500 mg thrice daily for 7 days with a combination of MFNS 50 μg 2 puff in each nostril two times a day for 7 days.
Detailed history using questionnaires for the patient's symptoms was taken, and any obstructive and infective causes were noted. Detailed clinical examination of nose (anterior rhinoscopy, posterior rhinoscopy), ear, throat, head, and neck examination thoroughly for any infective or obstructive cause was performed to confirm the diagnosis of ARS and probable etiology. The efficacy of treatment was assessed in terms of the Sino-Nasal Outcome Test-22 questionnaire. Patients were prescribed the same brand of drug. Patients not showing signs of improvement within 3 days or patients showing signs of complication were treated with higher antibiotics and withdrawn from the study.
Software Package for Statistical Analysis (SPSS) windows version 16 was used for data analysis. The graphical representations as pie chart, bar diagram, and line diagram were used for the presentation of gender, age, and symptoms score of patients before and after the treatment. Wilcoxon signed-rank test was used to compare the before and after treatment in each group. Mann-Whitney U was used to analyze the comparison of treatment between groups A and B. A p-value of < 0.05 was considered significant.
Gender distribution of patients
One-hundred twenty patients were included in this study. Among them, there were 81 females (67.5%) and 39 males (32.5%).
In group A, there were 21 (58.1%) male and 39 (41.9%) female patients, and in group B, there were 30% male (18) and 70% female (42).
The age of the patients ranged from 13 to 64 years with a mean age of 28.61 ± 11.73. The mean age of patients of group A was 27.48 ± 12.62 years and that of group B was 29.73 ± 10.76 years. The majority of patients were in the 18–35 years age group, i.e., 67 (55.8%), followed by patients in the age group of 36–55 years, i.e., 22 (19.3%) patients (Fig. 1).
Different age groups in patients
The mean score before the treatment was 21.32 ± 11.29 and after the treatment with amoxicillin was 9.37 ± 6.55 with a mean difference of 11.95 ± 7.41 (Fig. 2). Wilcoxon signed-rank test was used, and the mean decrease in score was found to be statistically significant with a p-value (< 0.001) (Table 1).
Mean score of individual symptoms from SNOT-22 score in both groups. Blue color represents before treatment score, and orange color represents after treatment score. A Comparison of before and after treatment individual mean SNOT-22 score in group A patients. B Comparison of before and after treatment individual mean SNOT-22 score in group B patients. The mean score of all the symptoms was reduced in both groups
Table 1 Mean SNOT-22 score before and after treatment in group A
The mean score before the treatment was 26.68 ± 11.97 and after the treatment with amoxicillin and MFNS was 3.07 ± 3.46 with a mean difference of 23.61 ± 10.86. Wilcoxon signed-rank test was used, and the mean decrease in score was found to be statistically significant with a p-value (< 0.001) (Table 2).
Table 2 Mean SNOT-22 score before and after treatment in group B
It was found that after treatment, the mean score with the amoxicillin group was 9.31 ± 6.55 and that of amoxicillin with the MFNS group was 3.07 ± 3.46, and their mean difference was 6.3 ± 0.95. Mann-Whitney U test was used, and the mean decrease in score was found to be statistically significant (p < 0.001) (Table 3).
Table 3 Comparison between mean SNOT-22 of group A and group B
This study included 120 patients who presented with symptoms of rhinosinusitis. All patients were diagnosed clinically and treated either with amoxicillin alone or with a combination of mometasone furoate nasal spray and amoxicillin.
This study demonstrated that MFNS administered twice a day along with antibiotics would help patients to get relief of symptoms in patients with ARS and help them to return to their day-to-day activity as earliest as possible.
In the study conducted by Meltzer et al., patients were treated for 21 days with amoxicillin clavulanate potassium and randomized to receive concurrent mometasone furoate nasal spray (MFNS) 400 μg, twice daily in 200 patients or placebo spray, and twice daily in 207 patients. Patient-recorded twice-daily symptom scores showed that adjunctive treatment with MFNS caused a significantly greater decrease in total symptom scores and in individual scores of inflammatory symptoms associated with the obstruction process (headache, congestion, and facial pain) compared with placebo [17].
Nayak et al. conducted a study, in which 967 outpatients with computed tomographic scan-confirmed moderate to severe rhinosinusitis received amoxicillin clavulanate 875 mg, twice daily, for 21 days with adjunctive twice-daily MFNS 200 μg, MFNS 400 μg, or placebo nasal spray. As adjunctive therapy to oral antibiotic treatment, MFNS at doses of 200 μg or 400 μg, twice daily, was well tolerated and significantly more effective in reducing the symptoms of rhinosinusitis than antibiotic therapy alone [9].
In our study, the age ranged from 13 to 64 years with the mean age being 28.6 years. In a study done by Nayak et al. [9], the mean age of patients was 39 years, and the age ranged from 8 to 78 years. In another study done by Meltzer et al. [17] in 2000, the mean age of patients was 40.3 years, and the age ranged from 12 to 73 years. In a similar study conducted by Meltzer et al. [18] in 2005, the mean age of patients was 35 years. The majority of patients in our study were in the age group of 18–35 years, i.e., 67 (55.8%) followed by patients in the age group of 36–55 years, i.e., 22 (19.3%) patients. Similar to our study in all the abovementioned studies, the mean age of the patients was in the adult group; we can say that ARS is more common in adults.
In our study, among 120 patients, most of them were females, i.e., 67.5% (81), and 32.5% were males (39) with male to female ratio being 1:2. The study conducted by Meltzer et al. in 2000 had 64% females (260) and 36% males (147) with male to female ratio being 1:1.7 [17]. In the study conducted by Nayak et al., there were 58.4% females (564) and 41.6% males (403) with male to female ratio being 1:1.4 [9]. Similar to this study, all the abovementioned studies had a higher incidence of ARS among females. Also, in all the abovementioned studies, most of the patients were in the reproductive age group. Females tend to have more close contact with young children who are more prone to upper respiratory tract infections. Therefore, females in their reproductive age group were more prone to acquire ARS.
In our study, there was a significant improvement in symptoms of blockage of the nose, thick nasal discharge, and facial pain in both groups. Similar to the abovementioned study, there was a decrease in the mean score of blockage of the nose, thick nasal discharge, and facial pain in both groups. However, there was a greater improvement in the symptom in patients using amoxicillin with MFNS (Fig. 3).
Mean total SNOT-22 score of groups A and group B before and after treatment. Blue color represents all patients receiving the treatment. Red color represents all patients in group A. Green color represents all patients in group B. The overall SNOT-22 mean score in all patients before the treatment was 24 ± 11.87 and after the treatment was 6.22 ± 6.1. The overall SNOT-22 mean score in patients before the treatment in groups A and group B was 21.32 ± 11.29 and 26.68 ± 11.92, respectively. The overall SNOT-22 mean score in patients after the treatment in group A was 9.37 ± 6.55 and in group B was 3.07 ± 3.46. The line graph shows greater improvement in the mean SNOT-22 after treatment in patients in group B receiving amoxicillin and mometasone furoate nasal spray
In our study, there was a significant improvement in cough and postnasal discharge in both groups. However, the study conducted by Nayak et al. [9] and Meltzer et al.27 in 2000 did not show a significant improvement in symptoms in amoxicillin with the MFNS group compared to the amoxicillin group.
Our study was able to see the effect of ARS on a patient's life causing a troublesome impact on daily activities. Symptoms like difficulty falling asleep, waking up at night, lack of a good night's sleep, waking up tired, fatigue during the day, reduced productivity, reduced concentration, frustration, sad, and embarrassed were assessed. All the patients receiving MFNS had significant improvement in these symptoms.
Our study showed significant improvement in overall SNOT-22 symptoms score in patients receiving MFNS with amoxicillin. It was similar to the studies conducted by Nayak et al. and Meltzer et al. in 2000 that showed an addition of intranasal corticosteroid; MFNS to antibiotics significantly reduces symptoms of acute rhinosinusitis compared with amoxicillin alone [9, 17].
In this study, there was an improvement in symptoms of ARS in both the groups receiving amoxicillin alone or amoxicillin combined with MFNS. We can conclude that amoxicillin alone or amoxicillin combined with MFNS was effective in reducing the symptoms of ARS. However, as adjunctive therapy to oral antibiotic treatment, mometasone furoate nasal spray was significantly more effective in reducing the symptoms of ARS than antibiotic therapy alone.
ARS:
Acute rhinosinusitis
MFNS:
NMCTH:
Nepal Medical College and Teaching Hospital
PNS:
Paranasal sinuses
Upper respiratory infection
Benninger MS (2008) Scott-Brown's otorhinolaryngology, head and neck surgery. In: Gleeson M, Browing GG, Burton MJ, et al. (eds) Rhinosinusitis, 7th edn. Edward Arnold Publications, London.
Passali D, Spinosi MC, Crisanti A, Bellussi LM (2016) Mometasone furoate nasal spray: a systematic review. Multidiscip Respir Med 11:18. https://doi.org/10.1186/s40248-016-0054-3
Almutairi A, Shafi R, Albalawi S, Basyuni M, Alzahrnai A, Alghamdi A, Alhaifi A, Alshehri A, Al-Gadouri M (2017) Acute and chronic sinusitis causes and management. Egypt J Hosp Med 68(3):1513–19. https://doi.org/10.12816/0039697
Rosenfeld RM, Andes D, Bhattacharyya N, Cheung D, Eisenberg S, Ganiats TG, Gelzer A, Hamilos D, Haydon RC 3rd, Hudgins PA, Jones S, Krouse HJ, Lee LH, Mahoney MC, Marple BF, Mitchell CJ, Nathan R, Shiffman RN, Smith TL, Witsell DL (2007) Clinical practice guideline: adult sinusitis. Otolaryngol Head Neck Surg 137(3):S1-31. https://doi.org/10.1016/j.otohns.2007.06.726
Gwaltney JM, Wiesinger BA, Patrie JT (2004) Acute community-acquired bacterial sinusitis: the value of antimicrobial treatment and the natural history. Clin Infect Dis 38:227–33. https://doi.org/10.1086/380641
Heikkinen T, Jarvinen A (2003) The common cold. Lancet 361:51–9. https://doi.org/10.1016/S0140-6736(03)12162-9
Payne SC, Benninger MS (2007) Staphylococcus aureus is a major pathogen in acute bacterial rhinosinusitis: a meta-analysis. Clin Infect Dis 45:e121-7. https://doi.org/10.1086/522763
Berg O, Carenfelt C, Rystedt G, Anggard A (1986) Occurrence of asymptomatic sinusitis in common cold and other acute ENT-infections. Rhinology 24:223–5
Nayak AS, Settipane GA, Pedinoff A, Charous BL, Meltzer EO, Busse WW, Zinreich SJ, Lorber RR, Rikken G, Danzig MR (2002) Effective dose range of mometasone furoate nasal spray in the treatment of acute rhinosinusitis. Ann Allergy Asthma Immunol 89:271–8. https://doi.org/10.1016/S1081-1206(10)61954-0
Fokkens WJ, Lund VJ, Mullol J et al (2020) European position paper on rhinosinusitis and nasal polyps 2020. Rhinology 29:1–464. https://doi.org/10.4193/Rhin20.600
Barlan IB, Erkan E, Bakir M, Berrak S, Basaran MM (1997) Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children. Ann Allergy Asthma Immunol 78:598–601. https://doi.org/10.1016/S1081-1206(10)63223-1
Barton BE, Jakway JP, Smith SR, Siegel MI (1991) Cytokine inhibition by a novel steroid, mometasone furoate. Immunopharm Immunotox 13:251–61. https://doi.org/10.3109/08923979109019704
Yilmaz G, Varan B, Yilmaz T, Gurakan B (2000) Intranasal budesonide spray as an adjunct to oral antibiotic therapy for acute sinusitis in children. Eur Arch Otorhinolaryngol 257:256–9. https://doi.org/10.1007/s004050050234
Qvarnberg Y, Kantola O, Salo J, Toivanen M, Valtonen H, Vuori E (1992) Influence of topical steroid treatment on maxillary sinusitis. Rhinology 30:103–12
Kennedy JL, Hubbard MA, Huyett P, Patrie JT, Borish L, Payne SC (2013) Sino-nasal Outcome Test (SNOT-22): a predictor of post-surgical improvement in patients with chronic sinusitis. Ann Allergy Asthma Immunol 111:246–51. https://doi.org/10.1016/j.anai.2013.06.033
Sahlstrand-Johnson P, Ohlsson B, Von Buchwald C, Jannert M, Ahlner-Elmqvist M (2011) A multi-centre study on quality of life and absenteeism in patients with CRS referred for endoscopic surgery. Rhinology 49(4):420–8. https://doi.org/10.4193/Rhino11.101
Meltzer EO, Charous BL, Busse WW, Zinreich SJ, Lorber RR, Danzig MR (2000) Added relief in the treatment of acute recurrent sinusitis with adjunctive mometasone furoate nasal spray. J Allergy Clin Immunol 106:630–7. https://doi.org/10.1067/mai.2000.109056
Meltzer EO, Bachert C, Staudinger H (2005) Treating acute rhinosinusitis: comparing efficacy and safety of mometasone furoate nasal spray, amoxicillin, and placebo. J Allergy Clin Immunol 116:1289–95. https://doi.org/10.1016/j.jaci.2005.08.044
No funding received
Otorhinolaryngology, Karuna Hospital Pvt, Kathmandu, Nepal
Sandeep Shrestha
Department of Otorhinolaryngology and Head and Neck Surgery, Nepal Medical College and Teaching Hospital, Kathmandu, Nepal
Rupesh Raj Joshi
Tilganga Institute of Ophthalmology, Kathmandu, Nepal
Swikriti Shrestha
SS has written all the articles under the guidance of RRJ. All data analysis, interpretation, and literature review were done by SS and SS under the guidance of RRJ. The authors read and approved the final manuscript.
Correspondence to Sandeep Shrestha.
The ethical approval was taken from the Institutional Review Committee (IRC) of Nepal Medical College and Teaching Hospital (NMCTH) before commencing the study. Consent to Participate: Informed written consent to participate in the study was provided by all the participants or parents/ guardians of patients under 16 years old.
Shrestha, S., Joshi, R.R. & Shrestha, S. Efficacy of mometasone furoate nasal spray in the treatment of acute rhinosinusitis. Egypt J Otolaryngol 39, 14 (2023). https://doi.org/10.1186/s43163-023-00380-9
Acute rhinosinusitis (ARS)
Mometasone furoate nasal spray (MFNS)
Sino-Nasal Outcome Test-22 (SNOT-22)


Nelson Mandela was jailed for 27 years by the apartheid South African government for his fight against its racist policies. He then served as President of South Africa from 1994 to 1999. He has had hundreds of structures and awards named after him in his home country and the rest of the world. They include streets, municipalities, bridges, squares, parks, gardens, plants and animals. This list is in no particular order.
Marine biologists Angel Vlades and Terry Gosliner found the sea slug, Mandelia Micocornata in 1999. The two are quoted as saying: "It is regarded as something of an honor to have a species of organism named after you. To have a genus named after you is even more of an honor because new genera are less often named than new species. However, an even greater honor is to have a family named after you because new families are rarely created." They said they named it after Mandela to honor him.
In 2002 a new species of the small African orb-weaves spider was found near Cape Town and named in honor of Nelson Mandela. The small African orb-weaver is restricted to western, southern and central Africa. The genus is Singafrotupa and there are three know species, the Mandela being one.
The Mandela, a fundamental particle, was discovered in 1973 by Leeds University cosmic ray group. The particle was named Mandela Particle in honor of Nelson Mandela. The particle would be 40 to 70 times the mass of a proton and was proposed to explain by Leeds to explain an anomaly of their measurements of multi-TeV cosmic rays near sea-level.
The beautiful orchid Paravanda Nelson Mandela was named after former president Nelson Mandela when he visited the National Orchid Garden in Singapore March 1997.
A woodpecker species whose remains were unearthed by French and German scientists at the Langebaanweg fossil site on South Africa's south-west coast, named it Australopicus nelsonmandelai in honour of Nelson Mandela. It is the oldest type ever found on the African continent. "We have named the new species after Nelson Mandela — a sort of scientific present for his 94th birthday," said Albrecht Manegold from the Senckenberg Research Institute in Frankfurt. Australopicus nelsonmandelai is believed to have lived in the early Pliocene period about five to three million years ago. It was related to woodpecker species alive in the Americas and Eurasia today, and not to those found in Africa.
A music group in Venezuela is named "Danzas Mandela" in honor of Nelson Mandela. The group started in 1990 and is involved in music, dance and theater especially of the Barloventio region.
Stasimopus mandelai is a species of ctenizid trapdoor spider from the Eastern Cape Province of South Africa. This species occurs syntopically with S. schoenlandi and a number of other mygalomorph spiders at the Great Fish River Nature Reserve. The species was named in 2004 by zoologists Brent E Hendrixson and Jason E Bond "honoring Nelson Mandela, the former president of South Africa.
The Protea cynaroides cultivar 'Madiba' was named after former President Nelson Mandela, on occasion of his 80th birthday in 1998. Proteas are a genus of flowering plants found in South Africa and sometimes called sugarbushes. Madiba is the name of the African tride to which Mandela belongs and in South Africa it is a sign of honor and respect to call him Madiba.
"Only Fools and Horses" is a British sitcom which was originally aired on BBC between 1981 and 1991. The apartment in this sitcom was called The Nelson Mandela House. The main characters in the show lived in this apartment.
Strelitzia reginae 'Mandela's Gold' is a rare yellow form of the well-known crane flower, Strelitzia reginae. 'Mandela's Gold' is a stemless, evergreen clump-forming perennial. Greyish green, banana-like leaves grow to a height of about 1.5 m and during winter and spring the large bird-like flowers are held above the foliage on the tips of long, sturdy stalks.