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A report of two cases in Spain in men who have sex with men" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "248" "paginaFinal" => "250" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Caracterización fenotípica y genotípica de <span class="elsevierStyleItalic">Shigella sonnei</span> portadora de la betalactamasa de espectro extendido CTX-M-27. A propósito de dos casos en España en hombres que tienen sexo con hombres" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 926 "Ancho" => 2101 "Tamanyo" => 259157 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Identification of <span class="elsevierStyleItalic">Shigella</span> spp. and detection of the presence of an extended-spectrum beta-lactamase (ESBL).</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">(A) Left: TSI (triple sugar-iron) medium, glucose fermentation can be seen but not producing gas; right: LIA (lysine-iron agar) medium, there is no decarboxylation or deamination of the lysine. (B) Disc-diffusion technique with the confirmation kits "Total ESBL, AmpC and ESBL<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>AmpC Confirm kit" (ROSCO Diagnostica A/S, Taastrup, Denmark). The increase in the cefotaxime and ceftazidime halo (>5<span class="elsevierStyleHsp" style=""></span>mm) can be seen in the presence of clavulanic acid but not in cloxacillin, confirming the presence of ESBL.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Domingo Fernández Vecilla, Kristina Zugazaga Inchaurza, Itxaso Lombide Aguirre, José Luis Díaz de Tuesta del Arco" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Domingo" "apellidos" => "Fernández Vecilla" ] 1 => array:2 [ "nombre" => "Kristina" "apellidos" => "Zugazaga Inchaurza" ] 2 => array:2 [ "nombre" => "Itxaso" "apellidos" => "Lombide Aguirre" ] 3 => array:2 [ "nombre" => "José Luis" "apellidos" => "Díaz de Tuesta del Arco" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213005X22001483" "doi" => "10.1016/j.eimc.2022.06.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213005X22001483?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2529993X23000783?idApp=UINPBA00004N" "url" => "/2529993X/0000004100000004/v2_202304072117/S2529993X23000783/v2_202304072117/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Synergistic anti-malarial effects of <span class="elsevierStyleItalic">Ocimum sanctum</span> leaf extract and artemisinin" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "250" "paginaFinal" => "251" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "Zulvikar Syambani Ulhaq" "autores" => array:1 [ 0 => array:4 [ "nombre" => "Zulvikar Syambani" "apellidos" => "Ulhaq" "email" => array:2 [ 0 => "zulvikar.syambani.ulhaq@brin.go.id" 1 => "zulhaq@kedokteran.uin-malang.ac.id" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Research Center for Pre-Clinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong, Indonesia" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Biochemistry, Faculty of Medicine and Health Sciences, Maulana Malik Ibrahim Islamic State University of Malang, Batu, East Java, Indonesia" "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Efectos antipalúdicos sinérgicos del extracto de hoja de <span class="elsevierStyleItalic">Ocimum sanctum</span> y artemisinina" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2693 "Ancho" => 1676 "Tamanyo" => 242102 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Synergistic anti-malarial effects of <span class="elsevierStyleItalic">Ocimum sanctum</span> leaf extract and artemisinin. (A) Reduction of parasitemia. (B) TGF-β level by peritoneal macrophages during mice malaria infections measured by ELISA after 24<span class="elsevierStyleHsp" style=""></span>h <span class="elsevierStyleItalic">in vitro</span> culture. Data are expressed as a mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation (SD). (*) Indicates a significant difference compared to the baseline level or between two groups indicated in the graphs (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). OS1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.25<span class="elsevierStyleHsp" style=""></span>mg/g/day; OS2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.5<span class="elsevierStyleHsp" style=""></span>mg/g/day; ART<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>artemisinin 0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day; ART<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>OS1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>artemisinin 0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.25<span class="elsevierStyleHsp" style=""></span>mg/g/day; ART<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>OS2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>artemisinin 0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.5<span class="elsevierStyleHsp" style=""></span>mg/g/day; NC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>negative control; PC, positive control.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Malaria remains a major health problem in Indonesia. It has been reported that the prevalence of parasitemia in Timika, Papua was 16.3%, and almost 50% of cases were caused by <span class="elsevierStyleItalic">Plasmodium falciparum</span> (<span class="elsevierStyleItalic">P. falciparum</span>).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> Papua province has not only the highest prevalence of malaria in Indonesia but also the highest prevalence of multidrug-resistance to both <span class="elsevierStyleItalic">P. vivax</span> and <span class="elsevierStyleItalic">P. falciparum</span>.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">2</span></a> Although artemisinin-based combination therapy (ACT) was adopted as the first-line anti-malarial treatment, studies have demonstrated the failure of ACT towards malaria elimination in several Southeast Asian countries.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">3</span></a> Hence, an alternative combination therapy against malaria is needed.</p><p id="par0010" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Ocimum sanctum</span> (<span class="elsevierStyleItalic">O. sanctum</span>, Indonesian name Kemangi) belongs to the Lamiaceae family and is widely distributed throughout Indonesia. <span class="elsevierStyleItalic">O. sanctum</span> is used by Indonesian to treat several diseases, including malaria; however, the underlying mechanism remains elusive. A study revealed that the ethanolic leaf extract of <span class="elsevierStyleItalic">O. sanctum</span> displays more potent antiplasmodial activity than other Ocimum species <span class="elsevierStyleItalic">in vitro</span>.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Therefore, this study aims to evaluate the synergistic anti-malarial properties of <span class="elsevierStyleItalic">O. sanctum</span> and artemisinin (ART) against the <span class="elsevierStyleItalic">Plasmodium</span> infection <span class="elsevierStyleItalic">in vivo</span>. In addition, the level of transforming growth factor-beta (TGF-β) was examined.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The leaves of <span class="elsevierStyleItalic">O. sanctum</span> were collected from Malang, East Java, Indonesia. The species was identified and confirmed by a plant taxonomist of the herbarium unit, UPT Materia Medica, Batu, East Java, Indonesia. The ethanolic extract preparation was conducted as previously described.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> For <span class="elsevierStyleItalic">in vivo</span> experiments, female Balb/c mice between 8 and 12 weeks of age were used. Sixty-three mice were randomly assigned into seven groups (9 mice per group), namely negative control, positive control, infected mice treated with ART (0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day); two different doses of <span class="elsevierStyleItalic">O. Sanctum</span> extract (0.25 and 0.5<span class="elsevierStyleHsp" style=""></span>mg/g/day); and combinations of artemisinin and <span class="elsevierStyleItalic">O. Sanctum</span> extract. The malaria model was performed by i.p. injection of <span class="elsevierStyleItalic">Plasmodium berghei</span> adjusted to 10<span class="elsevierStyleSup">6</span> parasites in 0.2<span class="elsevierStyleHsp" style=""></span>mL blood per mouse. Infected mice were then treated on the sixth day of infection with parasitemia approximately around 10% for seven consecutive days. To examine TGF-β levels, mice peritoneal macrophages on day seven post-treatment were cultured as described previously,<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> and the supernatants were used to quantify the concentration of TGF-β (BioLegend) by ELISA.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">7–10</span></a> The study was approved by the medical ethics committee of Brawijaya University with Reference No. 27-KE. The reduction of parasitemia and TGF-β levels were analyzed by two and one-way ANOVA, respectively, followed by the Fisher LSD <span class="elsevierStyleItalic">post hoc</span> test using StatPlus. Significant differences were accepted when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The reduction of parasitemia was observed in all groups started on day five of the treatment. Notably, the administration of ART and <span class="elsevierStyleItalic">O. Sanctum</span> extract at a dose of 0.5<span class="elsevierStyleHsp" style=""></span>mg/g/day demonstrated a higher effectivity to speed up <span class="elsevierStyleItalic">Plasmodium</span> clearance than other groups (at day 3 compared to the baseline level, <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). Moreover, the suppression of TGF-β was only observed in mice treated with combination therapy but not with monotherapy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B), thereby implying that combination therapy exhibits synergistic anti-malarial effects towards <span class="elsevierStyleItalic">Plasmodium</span> elimination. Various active constituents have been identified in the ethanolic extract of <span class="elsevierStyleItalic">O. Sanctum,</span> such as alkaloids, glycosides, flavonoids, phenols, saponins, tannins, steroids, and triterpenoids.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> The possible mechanisms of <span class="elsevierStyleItalic">O. Sanctum</span> extract in eliminating <span class="elsevierStyleItalic">P. berghei</span> may have occurred through the inhibition of hemozoin biocrystallization, protein synthesis, or β-haematin formation, stimulation of DNA fragmentation, and cytoplasmic acidification.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">In line with previous findings, this study showed that the upregulation of TGF-β levels was observed in <span class="elsevierStyleItalic">P. berghei</span> infected mice. Furthermore, the upregulation of TGF-β is known to be associated with the risk of complicated malaria.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> These results imply that TGF-β is linked to the disease severity of malaria. Therefore, a treatment that modulates the suppression of TGF-β would be beneficial to minimize malaria progression. In summary, the combination of ART and the ethanolic extract of <span class="elsevierStyleItalic">O. Sanctum</span> displays synergistic anti-plasmodial activity <span class="elsevierStyleItalic">in vivo</span>. Further studies are warranted to investigate the potential of <span class="elsevierStyleItalic">O. Sanctum</span> as an alternative ACT regimen in clinical settings.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Authors’ contribution</span><p id="par0030" class="elsevierStylePara elsevierViewall">Z.S.U. conceived, performed, analyzed, and wrote the article.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0035" class="elsevierStylePara elsevierViewall">N/A.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflict of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">None to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Authors’ contribution" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Funding" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflict of interest" ] 3 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2693 "Ancho" => 1676 "Tamanyo" => 242102 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Synergistic anti-malarial effects of <span class="elsevierStyleItalic">Ocimum sanctum</span> leaf extract and artemisinin. (A) Reduction of parasitemia. (B) TGF-β level by peritoneal macrophages during mice malaria infections measured by ELISA after 24<span class="elsevierStyleHsp" style=""></span>h <span class="elsevierStyleItalic">in vitro</span> culture. Data are expressed as a mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>standard deviation (SD). (*) Indicates a significant difference compared to the baseline level or between two groups indicated in the graphs (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). OS1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.25<span class="elsevierStyleHsp" style=""></span>mg/g/day; OS2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.5<span class="elsevierStyleHsp" style=""></span>mg/g/day; ART<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>artemisinin 0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day; ART<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>OS1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>artemisinin 0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.25<span class="elsevierStyleHsp" style=""></span>mg/g/day; ART<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>OS2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>artemisinin 0.036<span class="elsevierStyleHsp" style=""></span>mg/g/day<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">O. Sanctum</span> 0.5<span class="elsevierStyleHsp" style=""></span>mg/g/day; NC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>negative control; PC, positive control.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The risk of morbidity and mortality following recurrent malaria in Papua, Indonesia: a retrospective cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Dini" 1 => "N.M. Douglas" 2 => "J.R. Poespoprodjo" 3 => "E. Kenangalem" 4 => "P. Sugiarto" 5 => "I.D. 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