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Carbapenem resistance is a serious public health threat, causing numerous deaths annually primarily due to healthcare-associated infections. To face this menace, surveillance programs in high-risk patients are becoming a widespread practice. Here we report the performance of the combined use of a recently approved commercial multiplex real-time PCR assay (REALQUALITY Carba-Screen kit) with conventional phenotypic screening. In this three-month study, 479 rectal swabs from 309 patients across high-risk units were evaluated by combining the two approaches. Although the molecular assay showed a higher positivity rate than phenotypic screening (7.1% vs. 5%), it should be noted that the molecular method alone would have missed eight carbapenem-resistant isolates, while using only phenotypic screening would not have detected sixteen isolates. This demonstrates the complementary strengths of each method. Our study confirms the need for a combined approach to maximize the possible clinical impact of this kind of screening, ensuring a more comprehensive detection of resistant strains.
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The SARS-CoV-2 pandemic is ongoing worldwide, causing prolonged pressure on molecular diagnostics. Viral antigen (Ag) assays have several advantages, ranging from lower cost to shorter turnaround time to detection. Given the rare occurrence of low-load viremia, antigen assays for SARSCoV-2 have focused on nasopharyngeal swab and saliva as biological matrices, but their effectiveness must be validated. We assayed here the performances of the novel quantitative Liaison® SARSCoV-2 Ag assay on 119 nasopharyngeal swabs and obtained results were compared with Hologic Panther and Abbott m2000 RT-qPCR. The Ag assay demonstrated a good correlation with viral load, shorter turnaround time, and favorable economics. The best performance was obtained in the acute phase of disease.
Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Nasofaringe , Pandemias , Saliva , Sensibilidade e EspecificidadeAssuntos
COVID-19/patologia , SARS-CoV-2 , Tireoidite Autoimune/patologia , Anticorpos Monoclonais Humanizados/imunologia , Anticorpos Monoclonais Humanizados/farmacologia , Feminino , Genoma Viral/genética , Humanos , Itália , Pessoa de Meia-Idade , Peru , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/virologia , Organização Mundial da SaúdeRESUMO
We report 11 cases of SARS-CoV-2 infection in healthcare workers (HCW) naïve for COVID-19 and seropositive after the second dose of the BNT162b2 mRNA vaccine. Based on voluntary-based surveillance, they tested positive for different strains of SARS-CoV-2, as Spike gene sequencing showed. Five of them reported mild symptoms. Given the risk for SARS-CoV-2 introduction from asymptomatic vaccinees, this case series suggests the need to continue nasopharyngeal screening programmes.
Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/genética , Vacinação , Adulto , Vacina BNT162 , COVID-19/virologia , Feminino , Pessoal de Saúde , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , SARS-CoV-2/genéticaRESUMO
BACKGROUND: Mood and metabolic disorders are interrelated and may share common pathological processes. Autonomic neurons link the brain with the gastrointestinal tract and constitute a likely pathway for peripheral metabolic challenges to affect behaviors controlled by the brain. The activities of neurons along these pathways are regulated by glia, which exhibit phenotypic shifts in response to changes in their microenvironment. How glial changes might contribute to the behavioral effects of consuming a high-fat diet (HFD) is uncertain. Here, we tested the hypothesis that anxiogenic and depressive-like behaviors driven by consuming a HFD involve compromised duodenal barrier integrity and subsequent phenotypic changes to glia and neurons along the gut-brain axis. METHODS: C57Bl/6 male mice were exposed to a standard diet or HFD for 20 weeks. Bodyweight was monitored weekly and correlated with mucosa histological damage and duodenal expression of tight junction proteins ZO-1 and occludin at 0, 6, and 20 weeks. The expression of GFAP, TLR-4, BDNF, and DCX were investigated in duodenal myenteric plexus, nodose ganglia, and dentate gyrus of the hippocampus at the same time points. Dendritic spine number was measured in cultured neurons isolated from duodenal myenteric plexuses and hippocampi at weeks 0, 6, and 20. Depressive and anxiety behaviors were also assessed by tail suspension, forced swimming, and open field tests. RESULTS: HFD mice exhibited duodenal mucosa damage with marked infiltration of immune cells and decreased expression of ZO-1 and occludin that coincided with increasing body weight. Glial expression of GFAP and TLR4 increased in parallel in the duodenal myenteric plexuses, nodose ganglia, and hippocampus in a time-dependent manner. Glial changes were associated with a progressive decrease in BDNF, and DCX expression, fewer neuronal dendritic spines, and anxiogenic/depressive symptoms in HFD-treated mice. Fluorocitrate (FC), a glial metabolic poison, abolished these effects both in the enteric and central nervous systems and prevented behavioral alterations at week 20. CONCLUSIONS: HFD impairs duodenal barrier integrity and produces behavioral changes consistent with depressive and anxiety phenotypes. HFD-driven changes in both peripheral and central nervous systems are glial-dependent, suggesting a potential glial role in the alteration of the gut-brain signaling that occurs during metabolic disorders and psychiatric co-morbidity.
Assuntos
Encéfalo/metabolismo , Encéfalo/patologia , Depressão/etiologia , Dieta Hiperlipídica/efeitos adversos , Duodeno/patologia , Transtornos Mentais/etiologia , Neuroglia/metabolismo , Animais , Peso Corporal , Duodeno/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Plexo Mientérico/metabolismo , Plexo Mientérico/patologia , Neuroglia/patologia , Neurônios/metabolismo , Neurônios/patologia , Gânglio Nodoso/metabolismo , Gânglio Nodoso/patologiaRESUMO
We report here an imported case of SARS-CoV-2 variant of concern B.1.1.351 (also known as 20H/501Y.V2 or "South African variant" or VOC 202012/02) in a 66-years old symptomatic male who returned from Malawi to Italy.
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COVID-19/virologia , SARS-CoV-2/isolamento & purificação , Idoso , Humanos , Itália , Malaui , Masculino , Filogenia , SARS-CoV-2/classificação , SARS-CoV-2/genética , SARS-CoV-2/fisiologia , ViagemRESUMO
We report an imported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 detected in an asymptomatic traveler who arrived in Italy on an indirect flight from Brazil. This case shows the risk for introduction of SARS-CoV-2 variants from indirect flights and the need for continued SARS-CoV-2 surveillance.
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COVID-19 , Doenças Transmissíveis Importadas , Programas de Triagem Diagnóstica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Adulto , Brasil/epidemiologia , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/virologia , Teste Sorológico para COVID-19/métodos , Portador Sadio/diagnóstico , Portador Sadio/epidemiologia , Doenças Transmissíveis Importadas/diagnóstico , Doenças Transmissíveis Importadas/epidemiologia , Doenças Transmissíveis Importadas/virologia , Programas de Triagem Diagnóstica/organização & administração , Programas de Triagem Diagnóstica/normas , Humanos , Itália/epidemiologia , Masculino , Mutação , SARS-CoV-2/genética , SARS-CoV-2/isolamento & purificação , Viagem/estatística & dados numéricos , Doença Relacionada a ViagensRESUMO
S100B protein bridges chronic mucosal inflammation and colorectal cancer given its ability to activate NF-kappaB transcription via RAGE signalling and sequestrate pro-apoptotic wtp53. Being an S100B inhibitor, pentamidine antagonizes S100B-wtp53 interaction, restoring wtp53-mediated pro-apoptotic control in cancer cells in several types of tumours. The expression of S100B, pro-inflammatory molecules and wtp53 protein was evaluated in human biopsies deriving from controls, ulcerative colitis and colon cancer patients at baseline (a) and (b) following S100B targeting with niosomal PENtamidine VEhiculation (PENVE), to maximize drug permeabilization in the tissue. Cultured biopsies underwent immunoblot, EMSA, ELISA and biochemical assays for S100B and related pro-inflammatory/pro-apoptotic proteins. Exogenous S100B (0.005-5 µmol/L) alone, or in the presence of PENVE (0.005-5 µmol/L), was tested in control biopsies while PENVE (5 µmol/L) was evaluated on control, peritumoral, ulcerative colitis and colon cancer biopsies. Our data show that S100B level progressively increases in control, peritumoral, ulcerative colitis and colon cancer enabling a pro-inflammatory/angiogenic and antiapoptotic environment, featured by iNOS, VEGF and IL-6 up-regulation and wtp53 and Bax inhibition. PENVE inhibited S100B activity, reducing its capability to activate RAGE/phosphor-p38 MAPK/NF-kappaB and favouring its disengagement with wtp53. PENVE blocks S100B activity and rescues wtp53 expression determining pro-apoptotic control in colon cancer, suggesting pentamidine as a potential anticancer drug.
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Carcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Pentamidina/administração & dosagem , Subunidade beta da Proteína Ligante de Cálcio S100/genética , Proteína Supressora de Tumor p53/genética , Antígenos de Neoplasias/genética , Biópsia , Carcinoma/genética , Carcinoma/patologia , Colo/efeitos dos fármacos , Colo/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/genética , Inflamação/patologia , Lipossomos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/genética , Mucosa/efeitos dos fármacos , NF-kappa B/genética , Microambiente Tumoral/efeitos dos fármacosRESUMO
Chronic inflammation and angiogenesis are associated with colonic carcinogenesis. Enteric glia-derived S100B protein has been proposed as an "ideal bridge", linking colonic inflammation and cancer, given its dual ability to up-regulate nuclear factor-kappaB (NF-κB) transcription via receptor for advanced glycation end products (RAGE) signaling and to sequestrate wild type pro-apoptotic wild type (wt)p53. However, its pro-angiogenic effects on cancer cells are still uninvestigated. To this aim, we evaluated the effect of exogenous S100B (0.05-5 µM) protein alone or in the presence of S100B blocking monoclonal antibody (mAb) (1:105-1:104 v/v diluted) on (1) cultured Caco-2 cells proliferation, migration and invasiveness in vitro, respectively by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)-formazan, wound healing and matrigel invasion assays and (2) its effect on the release of pro-angiogenic factors, such as vascular endothelial growth factor (VEGF) by ELISA and immunofluorescence analyses. The effect of S100B alone or in the presence of S100BmAb was then investigated on RAGE/pAkt/mammalian target of rapamycin (mTOR) signaling pathway by immunoblot analysis. Our results showed that S100B markedly increases proliferation and invasiveness of Caco-2 cells, through the release of pro-angiogenic VEGF and NO paralleled to a significant decrease of wtp53 expression mediated by RAGE-p38 mitogen-activated protein kinase (MAPK)/pAkt-mTOR and hypoxia-inducible factor 1-alpha (HIF1α) pathways. Such effects were counteracted by S100BmAb, indicating that S100B targeting is a potential approach to inhibit colon carcinoma proliferation and angiogenesis.
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Proteínas Angiogênicas/metabolismo , Neoplasias do Colo/metabolismo , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Transdução de Sinais , Células CACO-2 , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Because histamine is a modulator of cancer cell proliferation and invasiveness, this study aimed at investigating the effect of Lathyrus sativus-derived diamine oxidase (LSAO) and its mechanism of action on Caco-2 cell line, considering that LSAO catalizes the oxidative deamination of histamine to the corresponding aldehyde, NH3 and H2 O2 . Histamine (0.01-1 µM) caused a proliferative effect on Caco-2 cells promoting cell migration, invasion and nitric oxide and vascular endothelial growth factor release. Histamine (1 µM) stimulus also down regulated occludin expression, favouring up regulation of pro-proliferative nuclear protein Ki67. Incubation with LSAO (0.004-0.4 µM) resulted in a significant inhibition of histamine-induced effects. LSAO rescued occludin expression and down regulated Ki67, and it inhibited histamine-induced increase of both MMP-2 and 9 expression. Histamine effects were mediated by RhoA-GTP down regulation and inversely related to phospho-p38MAPK/p50/65 up regulation. These effects were counteracted by LSAO incubation. Histamine catabolism by LSAO accounts for a significant down regulation of proliferation and invasiveness of Caco-2 cells. This study highlights the importance to control histamine levels in contrasting pro-angiogenic and metastatization capability of colon cancer cells and expands the knowledge about the diamine oxidase from L. sativus seeding as a phytotherapeutic approach for colon cancer.
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Amina Oxidase (contendo Cobre)/farmacologia , Neoplasias do Colo/tratamento farmacológico , Lathyrus/enzimologia , Neovascularização Patológica/tratamento farmacológico , Células CACO-2 , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/irrigação sanguínea , Histamina , HumanosRESUMO
Introduction: New investigations have shown that 'activated' enteric glial cells (EGCs), astrocyte-like cells of the enteric nervous system (ENS), represent a possible extra-CNS trigger point of the neurodegenerative processes in impaired intestinal permeability conditions. The early modulation of enteric glia-mediated neuroinflammation might optimize neuroprotective treatments outcomes currently used in neurodegenerative diseases. Areas covered: We discussed recent clinical and preclinical data existing on the Pubmed database, concerning the glial role in neurodegeneration. We focused on the gut as possible "entrance door" for endoluminal neurotoxic agents that induce neurological impairments during leaky gut conditions. Moreover, we reviewed the paradigmatic studies linking the leaky gut-induced priming of EGCs to the induction of late neurodegenerative processes in Parkinson's disease and other neurodegenerative disorders. Expert opinion: The previous appearance of neuropathological markers in the ENS emphasizes the extra-CNS origin of neurodegenerative disorders, by directing their therapies toward peripheral management of neurodegeneration. In light of the EGCs changes resulting from a switch-on of activated phenotype in leaky gut syndrome, EGCs sampling could be predictive for neuropathological conditions detection, anticipating their symptomatic manifestation in the CNS.