1,776 research outputs found

    The Effect of COVID-19 On Antibiotic Resistance

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    Over three years have passed since the beginning of the COVID-19 pandemic. During these times we have experienced significant changes in all areas of our life. In healthcare, more attention was focused on COVID-19 than other concerns. An unexpected consequence of the pandemic was a silent progression of an increased spread of multi-resistant pathogens. While antibiotic use during the pandemic varied across healthcare settings, antibiotics were prescribed for COVID-19 patients, even though antibiotics are known not to be effective against viruses.1 In dentistry, antibiotics were prescribed to prevent potential dental infections, since many dental offices were not open. Antimicrobial resistance was one of our greatest public health concerns prior to the COVID-19 pandemic, and it remains so

    Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

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    Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

    Iron content in forage sorghum (Sorghum bicolor (L.) Moench) measured on different slit widths with atomic absorption spectrometry

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    Our objective was to know the right slit width for iron (Fe) concentration of forage sorghum, sorghum hybrid (Sorghum bicolor (L.) Moench), and also to discern which water treatment sludge (WTS) were good for ruminant's health with the feeding sorghum on the present study. The present experiment was carried out on a randomized block design with four treatments; Control, alum sludge compost, alum sludge + NPK (nitrogen, phosphorus, potassium fertilizers), alum sludge compost + NPK (nitrogen, phosphorus, potassium fertilizers). Sorghum hybrid was harvested, and iron content of it was analyzed with an atomic absorption spectrophotometer on background correction (BGC) mode. In order to analyze the iron (Fe) content of the sorghum with the spectrophotometer, three different slit widths conditions were used; 0.15, 0.20 and 0.25 nm. Absorbance and background values were obtained during the Fe analyses with the apparatus. When the background value is small, it is preferred for some trace metals’ analyses. Both (AM/BS) ratio (mean of the absorbance values<AM> to the standard deviation of back ground values<BS>) and (AS<standard deviation of the absorbance values>/BS) ratio, were larger on 0.25 nm slit than those on 0.15 and 0.20 nm slit, and, from our experiment, the condition seemed better on the 0.25 nm slit for the iron analysis with the spectrophotometer. Therefore, the sorghum hybrid grown on (Alum+NPK) and on (Compost only) might be dangerous for ruminants because of their higher values than 200 mg Fe/kg DM (dry matter).Key words: Absorbance, alum sludge, atomic absorption spectrophotometer, background, forage sorghum hybrid, iron, slit

    An outbreak of post-acupuncture cutaneous infection due to Mycobacterium abscessus

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    BACKGROUND: Despite the increasing popularity of acupuncture, the importance of infection control is not adequately emphasized in Oriental medicine. In December 2001, an Oriental medical doctor in Seoul, South Korea, encountered several patients with persistent, culture-negative skin lesions on the trunk and extremities at the sites of prior acupuncture treatment. We identified and investigated an outbreak of Mycobacterium abscessus cutaneous infection among the patients who attended this Oriental medicine clinic. METHODS: Patients were defined as clinic patients with persistent cutaneous infections at the acupuncture sites. Medical records for the previous 7 months were reviewed. Clinical specimens were obtained from the patients and an environmental investigation was performed. M. abscessus isolates, cultured from patients, were compared by pulsed-field gel electrophoresis (PFGE). RESULTS: Forty patients who attended the Oriental medicine clinic and experienced persistent cutaneous wound infections were identified. Cultures from five of these patients proved positive, and all other diagnoses were based on clinical and histopathologic examinations. All environmental objects tested were negative for M. abscessus, however, most were contaminated by various nosocomial pathogens. Molecular analysis using PFGE found all wound isolates to be identical. CONCLUSION: We have identified a large outbreak of rapidly growing mycobacterial infection among patients who received acupuncture at a single Oriental medicine clinic. Physicians should suspect mycobacterial infections in patients with persistent cutaneous infections following acupuncture, and infection control education including hygienic practice, should be emphasized for Oriental medical doctors practicing acupuncture

    Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors

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    Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than it's HPV negative (HPV(-)) counterpart. This may be due to the higher numbers of tumor-infiltrating lymphocytes (TILs) in HPV positive (HPV(+)) tumors. RNA-Sequencing (RNA-Seq) was used to evaluate whether the differences in clinical behaviour simply reflect a numerical difference in TILs or whether there is a fundamental behavioural difference between TILs in these two settings. Thirty-nine HNSCC tumors were scored for TIL density by immunohistochemistry. After the removal of 16 TILlow tumors, RNA-Seq analysis was performed on 23 TILhigh/med tumors (HPV(+) n=10 and HPV(-) n=13). Using EdgeR, differentially expressed genes (DEG) were identified. Immune subset analysis was performed using Functional Analysis of Individual RNA-Seq/ Microarray Expression (FAIME) and immune gene RNA transcript count analysis. In total, 1,634 DEGs were identified, with a dominant immune signature observed in HPV(+) tumors. After normalizing the expression profiles to account for differences in B- and T-cell number, 437 significantly DEGs remained. A B-cell associated signature distinguished HPV(+) from HPV(-) tumors, and included the DEGs CD200, GGA2, ADAM28, STAG3, SPIB, VCAM1, BCL2 and ICOSLG; the immune signal relative to T-cells was qualitatively similar between TILs of both tumor cohorts. Our findings were validated and confirmed in two independent cohorts using TCGA data and tumor-infiltrating B-cells from additional HPV(+) HNSCC patients. A B-cell associated signal segregated tumors relative to HPV status. Our data suggests that the role of B-cells in the adaptive immune response to HPV(+) HNSCC requires re-assessment

    A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

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    Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol
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