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Abstract Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutations.

OBJECTIVE: Herein we report clinical and virological data in a patient with COVID-19 infection and a prior history of kidney transplantation who had a good clinical recovery despite systemic infection. PATIENTS AND METHODS: Reverse transcriptase quantitative PCR analysis for the RdRp, N and E target genes detected viral RNA in different types of biological specimens. Whole viral genome sequences were obtained and analyzed from respiratory tract, feces and blood. RESULTS: Viral sequences showed high (~99.9%) homology with the Wuhan seafood market pneumonia virus. Phylogenetic analysis assigned of the SARS-CoV-2 strains to clade G. A rare variant in the orf1ab gene was present in both sequences, while a missense variant was detected only in viral RNA from stool. CONCLUSIONS: The evolution of the COVID-19 systemic infection in the patient presented here was favorable to the hypothesis that immunosuppressive therapy in organ transplant recipients might be involved in viral dissemination. A missense mutation was present in only one specimen from the same patient implying the occurrence of a mutational event in viral RNA, which is suggestive for the presence of an active virus, even though viral isolation is necessary to demonstrate infectivity. [ABSTRACT FROM AUTHOR]

TP53 missense mutations are frequent driver events during tumorigenesis. The majority of TP53 mutations are missense and occur within the DNA binding domain of p53, leading to expression of mutant p53 (mut-p53) proteins that not only lose the tumor suppressive functions of the wild-type (wt-p53) form, but can also acquire novel oncogenic features fostering tumor growth, metastasis and chemoresistance. Mut-p53 affects fundamental cellular pathways and functions through different mechanisms, a major one being the alteration of gene expression. In our recent work (Capaci et al., 2020, Nat Commun) we found that mut-p53, via miR-30d, modifies structure and function of the Golgi apparatus (GA) and induces increased rate of trafficking. This culminates in the release of a pro-malignant secretome, which is capable of remodeling the tumor microenvironment (TME), to increase stiffness of the extracellular matrix (ECM), favouring metastatic colonization, as shown by cell-based assays and experiments of metastatic niche preconditioning in mouse xenograft models. This study provides new insights into the mechanisms by which mut-p53, through induction of non-coding RNAs, can exert pro-tumorigenic functions in a non-cell-autonomous fashion, and highlights potential non-invasive biomarkers and therapeutic targets to treat tumors harboring mut-p53 (Figure 1).

p53 mutants can promote tumorigenesis by affecting fundamental cellular pathways and functions. In this study, the authors demonstrate a novel mutant-p53/HIF1α/miR-30d axis that impacts Golgi structure, trafficking, and secretion of proteins essential for tumor growth and metastasis.

Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents TE mobilization-dependent neurodegeneration and cognitive defects. Mechanistically, PIN1 maintains nuclear type-B Lamin structure and anchoring function for heterochromatin protein 1α (HP1α). This mechanism prevents nuclear envelope alterations and heterochromatin relaxation under mechanical stress, which is a key contributor to aging-related pathologies.

TP53 mutations are widespread in human cancers. An expanding body of evidence highlights that, in addition to their manifold cell-intrinsic activities boosting tumor progression, missense p53 mutants enhance the ability of tumor cells to communicate amongst themselves and with the tumor stroma, by affecting both the quality and the quantity of the cancer secretome. In this review, we summarize recent literature demonstrating that mutant p53 enhances the production of growth and angiogenic factors, inflammatory cytokines and chemokines, modulates biochemical and biomechanical properties of the extracellular matrix, reprograms the cell trafficking machinery to enhance secretion and promote recycling of membrane proteins, and affects exosome composition. All these activities contribute to the release of a promalignant secretome with both local and systemic effects, that is key to the ability of mutant p53 to fuel tumor growth and enable metastatic competence. A precise knowledge of the molecular mechanisms underlying the interplay between mutant p53 and the microenvironment is expected to unveil non-invasive biomarkers and actionable targets to blunt tumor aggressiveness.

We describe MR imaging of bilateral infarction of the paramedian portion of the mesencephalus and thalamus due to an occlusion of the Percheron artery. This entity is due to one of the anatomic variants of the perforating arteries supplying the thalamus and mesenchephalus. Clinically this kind of infarction presents with neurologic impairment as a disorder of consciousness, memory dysfunctions, various types of vertical gaze palsy and psychic changes, which need to be differentiated from delirium and coma. At MRI evaluation infarction of the paramedian portion of thalami and midbrain, with a "butterfly wings" pattern, was demonstrated as high signal intensity areas on FLAIR and FSE-T2W images and with diffusion restriction on DWI images. [ABSTRACT FROM AUTHOR]

Introduction to Dossier. Fieldwork, the experimental and ethnographic “how to”

Mas que una estricta entrevista, este texto es una conversación con Renato Rosaldo en cuanto profesor universitario, antropólogo, chicano e individuo. Se destacan especialmente tres aspectos: su biografía, el estudio de los chicanos y la crisis de la antropología. Tuvo lugar en Palo Alto, Stanford el 15 y 16 de enero de 2001 tras un largo periodo de intenso diálogo entre los dos. El tema constante es la identidad en todas sus formas y las múltiples posibilidades de representación de esta identidad.

Entrevista realizada a Néstor García Canclini en el año de 2008 sobre los resultados de su investigación en Tijuana, México.

In occasione dell'incontro nazionale statunitense degli architetti, mi hanno chiesto di collaborare come artista-antropologa alla mostra che si sarebbe tenuta per l'evento, di sviluppare un rapporto interdisciplinare che desse il senso della artificialità delle frontiere; anche di quelle teoriche che vorrebbero definire in modo esageratamente limitante dove inizia l'interpretazione artistica e dove finisce quella antropologica. In fondo il dramma dell'etnografo come dell'artista e' lo stesso: quello della rappresentabilità dei vari mondi di cui siamo costituiti e di quelli circostanti. Dunque mi sono chiesta a lungo come rappresentare con un linguaggio che non fosse il mio solito, quello della scrittura, una frontiera tanto complessa. Ho optato per la fotografia digitale e per un gioco di specchi tanto apparentemente semplice quanto sostanzialmente complesso.

Background: Italy has been the first European Country dealing with SARS-CoV-2, whose diffusion on the territory has not been homogeneous. Among Italian regions, Sardinia represented one of the lowest incidence areas, likely due to its insular nature. Despite this, the impact of insularity on SARS-CoV-2 genetic diversity has not been comprehensively described., Methods: In the present study, we performed the high throughput sequencing of 888 SARS-CoV-2 genomes collected in Sardinia during the first 23 months of pandemics. In addition, 1439 high-coverage SARS-CoV-2 genomes circulating in Sardinia along three years (December 2019 - January 2023) were downloaded from GISAID, for a total of 2327 viral sequences that were characterized in terms of phylogeny and genomic diversity., Results: Overall, COVID-19 pandemic in Sardinia showed substantial differences with respect to the national panorama, with additional peaks of infections and uncommon lineages that reflects the national and regional policies of re-opening and the subsequent touristic arrivals. Sardinia has been interested by the circulation of at least 87 SARS-CoV-2 lineages, including some that were poorly represented at national and European level, likely linked to multiple importation events. The relative frequency of Sardinian SARS-CoV-2 lineages has been compared to other Mediterranean Islands, revealing a unique composition., Conclusions: The genomic diversity of SARS-CoV-2 in Sardinia has been shaped by a complex interplay of insular geography, low population density, and touristic arrivals, leading on the one side to the importation of lineages remaining rare at the national level, and resulting on the other side in the delayed entry of otherwise common variants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aims: In this study, five essential oils (EOs) from different species of Lavandula hybrida abrialis , for Lavandula hybrida R.C., Lavandula hybrida 'super A', Lavandula hybrida 'super Z' and Lavandula vera and its hybrids Lavender were evaluated against 26 dust-isolated fungal strains from North Africa., Methods and Results: The composition of the different EOs was determined from volume to dry weight. The photochemical analyses were performed via gas chromatography (GC). The cytotoxic effect of five lavender EOs on human epithelial colorectal adenocarcinoma cells (Caco-2) cell line was done. A total of 26 strains of filamentous fungi including Aspergillus spp. , Botrytis cinerea , Ceriporia spp. , Fusarium spp. and Penicillium glabrum were isolated from sand dust samples via molecular diagnostic tool of PCR. Fungal strains with the lowest minimal lethal concentration (MLC) were Penicillium glabrum, Ceriporia spp. and a strain of Aspergillus spp., Conclusions: More studies are needed to verify the activity of this EO against more different fungal species, and determine the active ingredients. Significance and impact of study: MIC of the antifungal efficacy relating to EOs was evaluated. The EOs tests showed no cytotoxic effect at very low concentrations, ranging from 0.03% (IC 50 0.9132 mg/mL) ( L. hybrid Abrialis) to 0.001% (IC 50 1.631 mg/mL) ( L. hybrid R.C.).

Background: The goal of this study was to monitor the microbial biodiversity in beach sand that is heavily visited by tourists during the summer, and to determinate whether the high presence of bathers (around 5000 per day) can modify sand microbial composition., Methods: Between 2016 and 2020, 150 sand samples were collected from nine different points at La Pelosa beach in Sardinia, Italy. Non-culturing methods were used; DNA extraction and meta-barcode sequencing were performed. All samples were analyzed with sequencing methods for 16S and ITS sequences., Results: Fungal genera differ on the three beaches and in the winter/summer zones. The ITS sequence showed the most common presence of Candida during summer and Paradendryphiella in the winter. The greatest diversity was found in the dune during winter, while in other parts of the beach, there are differences between bacteria and fungi, particularly in the wash zone during the winter, with high diversity for 16S sequences but low diversity for ITS sequences., Conclusions: It appears reasonable that the sands, even on non-urban beaches, should be included in health monitoring programs in addition to the waters, and that access to them should be regulated by limiting the number of bathers with the aim of reducing the presence of pathogenic fungal species.

Globally, antibiotic-resistant Klebsiella spp. cause healthcare-associated infections with high mortality rates, and the rise of hypervirulent Klebsiella pneumoniae (hv Kp ) poses a significant threat to human health linked to community-acquired infections and increasing non-susceptibility. We investigated the phenotypic and genetic features of 36 Klebsiella isolates recovered from invasive infections at Hospital Central of Maputo in Mozambique during one year. The majority of the isolates displayed multidrug resistance (MDR) (29/36) to cephalosporins, gentamicin, ciprofloxacin, and trimethoprim-sulfamethoxazole but retained susceptibility to amikacin, carbapenems, and colistin. Most isolates were ESBLs-producing (28/36), predominantly carrying the bla CTX-M-15 and other beta-lactamase genes ( bla SHV , bla TEM-1 , and bla OXA-1 ). Among the 16 genomes sequenced, multiple resistance genes from different antibiotic classes were identified, with bla CTX-M-15 , mostly in the IS Ecp1 - bla CTX-M-15 - orf477 genetic environment, co-existing with bla TEM-1 and aac(3)-IIa in five isolates. Our results highlight the presence of polyclonal MDR ESBL-producing K. pneumoniae from eight sequence types (ST), mostly harbouring distinct yersiniabactin within the conjugative integrative element (ICE). Further, we identified susceptible hv Kp ST23, O1-K1-type isolates carrying yersiniabactin ( ybt1 /ICEKp10), colibactin, salmochelin, aerobactin, and hypermucoid locus ( rmpADC ), associated with severe infections in humans. These findings are worrying and underline the importance of implementing surveillance strategies to avoid the risk of the emergence of the most threatening MDR hv Kp .

Microbial secondary infections can contribute to an increase in the risk of mortality in COVID-19 patients, particularly in case of severe diseases. In this study, we collected and evaluated the clinical, laboratory and microbiological data of COVID-19 critical ill patients requiring intensive care (ICU) to evaluate the significance and the prognostic value of these parameters. One hundred seventy-eight ICU patients with severe COVID-19, hospitalized at the S. Francesco Hospital of Nuoro (Italy) in the period from March 2020 to May 2021, were enrolled in this study. Clinical data and microbiological results were collected. Blood chemistry parameters, relative to three different time points, were analyzed through multivariate and univariate statistical approaches. Seventy-four percent of the ICU COVID-19 patients had a negative outcome, while 26% had a favorable prognosis. A correlation between the laboratory parameters and days of hospitalization of the patients was observed with significant differences between the two groups. Moreover, Staphylococcus aureus, Enterococcus faecalis, Candida spp, Pseudomonas aeruginosa and Klebsiella pneumoniae were the most frequently isolated microorganisms from all clinical specimens. Secondary infections play an important role in the clinical outcome. The analysis of the blood chemistry tests was found useful in monitoring the progression of COVID-19., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Introduction: Candida spp. are responsible for infections ranging from local to systemic, and resistance to antifungal first-line therapy is increasing in non-albicans Candida species. We aimed to determine the etiology of candidiasis and the antifungal resistance of Candida spp. isolated in Hue hospitals, Central-Vietnam., Methods: Species identification was performed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry supported by fungal internal-transcribed-spacer amplification and sequencing. Antifungal susceptibility testing was performed by disk diffusion method and minimum inhibitory concentrations of azoles, caspofungin, and amphotericin B against C. tropicalis were determined by broth microdilution. Polymorphism of erg11 gene associated with fluconazole resistance was carried out by polymerase chain reaction and sequencing. Multilocus sequence typing (MLST) was used for typing selected C. albicans isolates., Results: Overall, 196 Candida isolates were detected, mostly C. albicans (48%), followed by C. tropicalis (16%), C. parapsilosis (11%), C. glabrata (9%), C. orthopsilosis (6%) and to a lesser extent another eight species. High rates of resistance to fluconazole and voriconazole (18.8%) were observed in C. tropicalis with five isolates co-resistant to both agents. Y132F and S154F missense mutations in the ERG11 protein were associated with fluconazole-resistance in C. tropicalis (67.7%). Resistance to caspofungin was found in one isolate of C. albicans. MLST identified a polyclonal population of C. albicans with multiple diploid sequence types, and with few lineages showing potential nosocomial spread., Conclusions: Resistance to triazole agents should be considered in C. tropicalis infections in the studied hospitals, and surveillance measures taken to avoid Candida diffusion., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Thi Minh Chau Ngo, Antonella Santona, Maura Fiamma, Phuong Anh Ton Nu, Thi Bich Thao Do, Piero Cappuccinelli, Bianca Paglietti.)

Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests.

Rare information is available on clinical Enterococcus faecium encountered in Sardinia, Italy. This study investigated the antimicrobial susceptibility profiles and genotypic characteristics of E. faecium isolated at the University Hospital of Sassari, Italy, using the Vitek2 system and PCR, MLST, or WGS. Vitek2 revealed two VanB-type vancomycin-resistant Enterococcus faecium (VREfm) isolates (MICs mg/L = 8 and ≥32) but failed to detect vancomycin resistance in one isolate (MIC mg/L ≤ 1) despite positive genotypic confirmation of vanB gene, which proved to be vancomycin resistant by additional phenotypic methods (MICs mg/L = 8). This vanB isolate was able to increase its vancomycin MIC after exposure to vancomycin, unlike the "classic" occult vanB -carrying E. faecium , becoming detectable by Vitek 2 (MICs mg/L ≥ 32). All three E. faecium had highly mutated vanB 2 operons, as part of a chromosomally integrated Tn 1549 transposon, with common missense mutations in VanH and VanB 2 resistance proteins and specific missense mutations in the VanW accessory protein. There were additional missense mutations in VanS, VanH, and VanB proteins in the vanB 2 -carrying VREfm isolates compared to Vitek2. The molecular typing revealed a polyclonal hospital-associated E. faecium population from Clade A1, and that vanB 2 -VREfm, and nearly half of vancomycin-susceptible E. faecium (VSEfm) analyzed, belonged to ST117. Based on core genome-MLST, ST117 strains had different clonal types (CT), excluding nosocomial transmission of specific CT. Detecting vanB 2 -carrying VREfm isolates by Vitek2 may be problematic, and alternative methods are needed to prevent therapeutic failure and spread.

Extended-spectrum β-lactamase (ESBL)-producing extraintestinal pathogenic Escherichia coli (ExPEC), particularly high-risk lineages, are responsible for severe infections and increased mortality and hospital costs worldwide, with a major burden in low-income countries. Here we determined the antimicrobial susceptibility and performed whole-genome sequencing of E. coli isolates from extraintestinal infections of patients during 2017-2018 at Maputo Central Hospital (Mozambique). Multidrug resistance was displayed by 71% of isolates (17/24). All isolates resistant to cefotaxime and ceftazidime were positive for ESBL genes (16/24; 67%) and were co-resistant to amoxicillin/clavulanate (14/16; 88%), piperacillin/tazobactam (8/16; 50%), gentamicin (12/16; 75%), trimethoprim/sulfamethoxazole (15/16; 94%) and ciprofloxacin (11/16; 69%). Several major high-risk ExPEC lineages were identified, such as H30Rx-ST131, fimH41-ST131, H24Rx-ST410, ST617, ST361 and ST69 harbouring bla CTX-M-15 , and H30R-ST131, ST38 and ST457 carrying bla CTX-M-27 . Dissemination of CTX-M transposition units (ISEcp1-bla CTX-M-15 -orf477 and ISEcp1-bla CTX-M-27 -IS903B) among different sequence types could be occurring through the mobility of IncF plasmids. Additionally, all H24Rx-ST410 isolates carried ISEcp1-mediated bla CMY-2 AmpC and specific mutations in PBP3/OmpC proteins, potentially contributing to carbapenem resistance even in the absence of carbapenemase genes. Genome analysis highlighted a high assortment of ExPEC/UPEC virulence-associated genes mainly involved in adhesion, invasion, iron uptake and secretory systems among isolates, and an ExPEC/EAEC hybrid pathotype (fimH27-ST131_O18-ac:H4) showing the highest virulence gene content. cgMLST showed clonality and closely related isolates, particularly among ST131 and ST410, suggesting hospital-acquired infections and long-term ward persistence. Our study provides new insights into ExPEC clones, urging measures to prevent and contain their diffusion in this hospital and Mozambique., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Eumycetoma is a chronic debilitating fungal disease endemic to tropical and subtropical regions, with Sudan featuring the highest eumycetoma incidence. Among the 50 species of fungi most commonly associated with eumycetoma Madurella mycetomatis (M. mycetomatis) is often referenced as the most common pathogen. However, there is an enormous knowledge gap related to this neglected disease and its pathogenesis, epidemiological features, and host-specific factors that could contribute to either the host susceptibility and resistance. In this study, we were able to utilize a metagenomic approach and samples collected from clinical black grains (BG) and familiar household environments aimed to assay both the habitat of eumycetoma-associated fungi and its possible connection with eumycetoma patients living in two different eumycetoma endemic villages within the White Nile State of Sudan. DNA sequencing targeting the fungal ITS2 domain was performed on soil, animal dung, housing walls and roofs, and Acacia-species thorn samples and compared with culture-dependent methods of fungal isolation. Additionally, we compared the soil samples obtained in the endemic zone with that from non-endemic zones, including Wagga village in Kassala State and Port Sudan suburb in Port Sudan State. Overall, a total of 392 Amplicon Sequence Variants (ASVs) were detected by ITS2 metagenomics Eumycetoma causative organisms accounted for 10% of total ASVs which included 11 genera: Exserohilum (2%), Aspergillus (1.7%), Curvularia (1%), Alternaria (0.9%), Madurella (0.5%), Fusarium (0.4%), Cladosporium (0.2%) Exophiala (0.15%), and, in a lesser extent, Microascus (0.05%) Bipolaris and Acremonium (0.01%) for each. Only five genera were identified by culture method, which included Fusarium (29%), Aspergillus (28%), Alternaria (2.5%), Bipolaris (1.6%), and Chaetomium (0.8%). M. mycetomatis was detected within all the studied patients' houses, accounting for 0.7% of total sequences. It was the first common eumycetoma-associated agent detected in soil samples and the third common in the dung and wall samples. In contrast, it was not detected in the roof or thorn samples nor in the soils from non-endemic regions. Exserohilum rostratum, Aspergillus spp and Cladosporium spp were detected in all samples. M. mycetomatis and other eumycetoma-associated fungal identified in the patients' black grains (BG) samples by metagenomics were identified in the environmental samples. Only Acremonium alternatum and Falciformispora senegalensis, responsible for eumycetoma in two patients were not detected, suggesting the infections in these patients happened outside these endemic areas. The soil, animal dung, and houses built from the same soil and dung are the main risk factors for M. mycetomatis infection in these endemic villages. Furthermore, the poor hygienic and environmental conditions, walking barefooted, and the presence of animals within the houses increase the risk of M. mycetomatis and other fungi causing eumycetoma., Competing Interests: The authors have declared that no competing interests exist.

Background: The SARS-CoV-2 pandemic stimulated an outstanding global sequencing effort, which allowed to monitor viral circulation and evolution. Nuoro province (Sardinia, Italy), characterized by a relatively isolated geographical location and a low population density, was severely hit and displayed a high incidence of infection., Methods: Amplicon approach Next Generation Sequencing and subsequent variant calling in 92 respiratory samples from SARS-CoV-2 infected patients involved in infection clusters from March 2020 to May 2021., Results: Phylogenetic analysis displayed a coherent distribution of sequences in terms of lineage and temporal evolution of pandemic. Circulating lineage/clade characterization highlighted a growing diversity over time, with an increasingly growing number of mutations and variability of spike and nucleocapsid proteins, while viral RdRp appeared to be more conserved. A total of 384 different mutations were detected, of which 196 were missense and 147 synonymous ones. Mapping mutations along the viral genome showed an irregular distribution in key genes. S gene was the most mutated gene with missense and synonymous variants frequencies of 58.8 and 23.5%, respectively. Mutation rates were similar for the S and N genes with one mutation every ∼788 nucleotides and every ∼712 nucleotides, respectively. Nsp12 gene appeared to be more conserved, with one mutation every ∼1,270 nucleotides. The frequency of variant Y144F in the spike protein deviated from global values with higher prevalence of this mutation in the island., Conclusion: The analysis of the 92 viral genome highlighted evolution over time and identified which mutations are more widespread than others. The high number of sequences also permits the identification of subclusters that are characterized by subtle differences, not only in terms of lineage, which may be used to reconstruct transmission clusters. The disclosure of viral genetic diversity and timely identification of new variants is a useful tool to guide public health intervention measures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Malune, Piras, Monne, Fiamma, Asproni, Fancello, Manai, Carta, Pira, Fancello, Rosu, Uras, Mereu, Mameli, Lo Maglio, Garau and Palmas.)

The development of carbapenem resistance in extraintestinal pathogenic Escherichia coli (ExPEC) has significant clinical implications, particularly in countries where second-line antimicrobials are not readily available, rendering treatments ineffective, and ExPEC infections untreatable. Thus, early detection of high-risk ExPEC lineages and raising awareness of the specific mechanisms underlying carbapenem resistance are mandatory for the selection of appropriate treatment options and the prevention of E. coli spread. This study aims to investigate the phenotypic and genotypic features of the first NDM-5 carbapenemase-producing ExPEC strain isolated from the blood of a patient admitted to the Maputo Central Hospital (MCH), in Mozambique. E. coli SSM100 isolate was identified by MALDI-TOF, it displayed high-level resistance to third generation cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides, performing antimicrobial susceptibilities testing by VITEK 2 system. E. coli SSM100 isolate was classified through whole-genome sequencing as ST405-D-O102: H6, a globally distributed lineage associated with antimicrobial resistance, carrying the bla NDM-5 gene located on an F1:A1:B49 plasmid, coharboring bla CTX-M-15, bla TEM-1, aadA2 , sul1 , and dfrA12 genes. In addition, mutations in gyrA (S83L and D87N), parC (S80I and E84V), and parE (I529L) conferring fluoroquinolone resistance were also found. Moreover, SSM100 isolate carried 88 virulence genes, of which 28 are reported to be associated with UPEC. The emergence of NDM-5 carbapenemase in a pandemic ST405-D-O102:H6 clone in Mozambique is of great concern. Locations of extended-spectrum β-lactamase determinants and NDM-5 carbapenemase gene on Inc F -plasmid can increase their spread reinforcing the need for antimicrobial surveillance and the urgent introduction of carbapenemase detection tests in diagnostic laboratories of the country.

Objective: The current study explored changes in trend of anaemia and BMI among currently pregnant nullipara adolescent women against socio-economic determinants in India from 2005 through 2015. The association between anaemia in currently pregnant nullipara adolescent women v. currently pregnant nullipara older women of reproductive age was also explored., Design: We used the 2005 and the 2015 nationally representative Indian Demographic and Health Surveys (DHS). The outcomes of interest, anaemia and BMI, were measured based on the DHS methodology following WHO standards and indicators. Place of residence, educational attainment and wealth quintiles were used as determinants in the analysis., Setting: India., Participants: In total, 696 adolescent girls from the India 2005 DHS and 3041 adolescent girls from the India 2015 DHS., Results: The 10-year transition from 2005 to 2015 showed differences between the least and most wealthy sections of society, with heaviest gains in anaemia reduction over time among the latter (from 50·0 to < 40·0 %). The odds of anaemia were significantly higher among the adolescent population when compared with adult women both in 2005 and in 2015 (OR = 1·2)., Conclusions: Despite an overall improvement in the prevalence of both BMI < 18·5 and anaemia among adolescents nullipara in India, the adjusted risk of anaemia in the latter category was still significantly higher as compared with their adult counterparts. Since the inequalities evidenced during the first round of DHS remained unchanged in 2015, more investments in universal health care are needed in India.

Background: Eumycetoma is a chronic subcutaneous granulomatous disease that is endemic in Sudan and other countries. It can be caused by eight different fungal orders. The gold standard diagnostic test is culture, however, culture-independent methods such as imaging, histopathological and molecular techniques can support diagnosis, especially in cases of negative cultures., Methods: The amplicon-based internal transcribed spacer 2 metagenomic technique was used to study black grains isolated from 14 tissue biopsies from patients with mycetoma. Furthermore, mycological culture and surgical biopsy histopathological examinations of grains were performed., Results: Madurella mycetomatis (n=5) and Falciformispora spp. (n=4) organisms were identified by culture and confirmed by metagenomics. Metagenomics recognised, at the species level, Falciformispora as Falciformispora tompkinsii (n=3) and Falciformispora senegalensis (n=1), while in culture-negative cases (n=5), Madurella mycetomatis (n=3), Falciformispora senegalensis (n=1) and Fusarium spp. (n=1) were identified. Interestingly, the metagenomics results showed a 'consortium' of different fungi in each sample, mainly Ascomycota phylum, including various species associated with eumycetoma. The microbial co-occurrence in eumycetoma showed the co-presence of Madurella with Trichoderma, Chaetomium, Malasseziales and Sordariales spp., while Falciformispora co-presented with Inocybe and Alternaria and was in mutual exclusion with Subramaniula, Aspergillus and Trichothecium., Conclusion: Metagenomics provides new insights into the aetiology of eumycetoma in samples with negative culture and into the diversity and complexity of grains mycobiota, calling into question the accuracy of traditional culture for the identification of causative agents., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the coronavirus disease 2019 (COVID-19) pandemic, which started as a severe pneumonia outbreak in Wuhan, China, in December 2019. Italy has been the first European country affected by the pandemic, registering a total of 300,363 cases and 35,741 deaths until September 24, 2020. The geographical distribution of SARS-CoV-2 in Italy during early 2020 has not been homogeneous, including regions severely affected as well as administrative areas being only slightly interested by the infection. Among the latter, Sardinia represents one of the lowest incidence areas likely due to its insular nature., Methods: Next-generation sequencing of a small number of complete viral genomes from clinical samples and their virologic and phylogenetic characterization was performed., Results: We provide a first overview of the SARS-CoV-2 genomic diversity in Sardinia in the early phase of the March-May 2020 pandemic based on viral genomes isolated in the most inner regional hospital of the island. Our analysis revealed a remarkable genetic diversity in local SARS-CoV-2 viral genomes, showing the presence of at least four different clusters that can be distinguished by specific amino acid substitutions. Based on epidemiological information, these sequences can be linked to at least eight different clusters of infection, four of which likely originates from imported cases. In addition, the presence of amino acid substitutions that were not previously reported in Italian patients has been observed, asking for further investigations in a wider population to assess their prevalence and dynamics of emergence during the pandemic., Conclusion: The present study provides a snapshot of the initial phases of the SARS-CoV-2 infection in inner area of the Sardinia Island, showing an unexpected genomic diversity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Piras, Grandi, Monne, Asproni, Fancello, Fiamma, Mameli, Casu, lo Maglio, Palmas and Tramontano.)

Competing Interests: Competing interests: The authors completed the ICMJE Unified Competing Interest form (available upon request from the corresponding author), and declare no conflicts of interest.

Competing Interests: Competing interests: All authors completed the ICMJE conflicts of interest form, available upon request from the corresponding author, and declare no conflicts of interest.

Introduction: Imported parasitosis, which do not require an invertebrate vector, are extremely dangerous and can lead to the occurrence of disease in currently parasite free areas. In the present study we report a case of multi-parasitic infection in a young immigrant from Ghana to Italy caused by filaria, Schistosoma sp. and Strongyloides sp., Case Presentation: A 27-year-old Ghanaian man attended the Hospital of Nuoro (Sardinia), Italy, at the end of August 2015, claiming pain to the kidney and hypertensive crisis; the patient presented with dyspnea and epistaxis, chronic itchy skin of the back, shoulders, arms and legs, anuria and high creatinine, metabolic acidosis and hypereosinophilic syndrome. Serological test for parasitic infections were done, and showed a marked positivity for filaria, Schistosoma sp. and Strongyloides sp. The patient started the treatment immediately with two doses per day of Bassado Antibiotic (tetracycline) for twenty days and then with a single dose of 3 mg of ivermectin that was repeated after 3 months., Conclusions: Immigrant patients from endemic areas who show clinical signs, such as a general itching on the back, shoulders and arms and legs, should have a thorough history in order to make early diagnosis and prevent further complications. Therefore, general practitioners and doctors in Europe and in other parasitosis non-endemic countries, should consider to test for parasites in any immigrant from endemic countries to aid in establishing the final diagnosis and prevent further complications., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2020 Maura Fiamma, Silvia S Longoni, Emmanuel E Siddig, Sonia Attene, Vito Astone, Antonio Nicoletti , Bianca Paglietti , Antonella Santona, Angela Fele, Riccardo Ivaldi, Francesco Logias.)

This study evidenced the presence of parasites in a cesspit of an aristocratic palace of nineteenth century in Sardinia (Italy) by the use of classical paleoparasitological techniques coupled with next-generation sequencing. Parasite eggs identified by microscopy included helminth genera pathogenic for humans and animals: the whipworm Trichuris sp., the roundworm Ascaris sp., the flatworm Dicrocoelium sp. and the fish tapeworm Diphyllobothrium sp. In addition, 18S rRNA metabarcoding and metagenomic sequencing analysis allowed the first description in Sardinia of aDNA of the human specific T. trichiura species and Ascaris genus. Their presence is important for understanding the health conditions, hygiene habits, agricultural practices and the diet of the local inhabitants in the period under study.

In this communication, a case of black grain eumycetoma produced by the fungus C. atrobrunneum is reported. The patient was initially misdiagnosed with M. mycetomatis eumycetoma based on the grains' morphological and cytological features. However, further aerobic culture of the black grains generated a melanised fungus identified as C. atrobrunneum by conventional morphological methods and by internal transcribed spacer 2 (ITS2) ribosomal RNA gene sequencing. This is the first-ever report of C. atrobrunneum as a eumycetoma-causative organism of black grain eumycetoma. It is essential that the causative organism is identified to the species level, as this is important for proper patient management and to predict treatment outcome and prognosis., Competing Interests: The authors have declared that no competing interests exist.

The fungal community of six sand samples from Saudi Arabia and Jordan deserts was characterized by culture-independent analysis via next generation sequencing of the 18S rRNA genes and by culture-dependent methods followed by sequencing of internal transcribed spacer (ITS) region. By 18S sequencing were identified from 163 to 507 OTUs per sample, with a percentage of fungi ranging from 3.5% to 82.7%. The identified fungal Phyla were Ascomycota, Basal fungi, and Basidiomycota and the most abundant detected classes were Dothideomycetes, Pezizomycetes, and Sordariomycetes. A total of 11 colonies of filamentous fungi were isolated and cultured from six samples, and the ITS sequencing pointed toward five different species of the class Sordariomycetes, belonging to genera Fusarium (F. redolens, F. solani, F. equiseti), Chaetomium (C. madrasense), and Albifimbria (A. terrestris). The results of this study show an unexpectedly large fungal biodiversity in the Middle East desert sand and their possible role and implications on human health., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)

Enterococcus faecium has become a globally disseminated nosocomial pathogen mainly because of acquisition and diffusion of virulence factors and multidrug resistance determinants, including glycopeptides, which are some of the last resort antimicrobials used to treat more serious infections common in high-risk patients. In this study we investigated and characterized hospital-associated (HA) E. faecium isolates collected at Hue Central Hospital, Vietnam. Our results highlighted the spread among hospital wards of a surprisingly heterogeneous multidrug-resistant E. faecium population comprising five different CC17-related sequence types (STs), of which 46% VREf carry the vanB gene. Whole genome sequencing of selected E. faecium isolates showed that VREf from different STs carried the same chromosomal integrated Tn1549-like transposon, with a highly mutated vanB2-operon, showing an increased level of vancomycin resistance (VanB phenotype) and able, in one isolate, to confer resistance to teicoplanin (VanA incongruent phenotype). Two unusual vanA/vanB 2 -type strains were detected within the vanB 2 -type ST17 population, harbouring a Tn1546-vanA-like transposon in pJEG40-like plasmids. Wg-SNPs-based analysis showed the genetic relatedness of VSEf/VREf of the same STs and indicated lateral exchange of the Tn1549-like element among isolates followed by clonal expansion. Microevolution among ST17 isolates, including the vanA/vanB 2 -type strains, and inter-wards VREf transmission, were highlighted. The use of teicoplanin is strongly discouraged in the study hospital because of the spreading of Tn1549-vanB 2 associated to teicoplanin resistance. A rational use of glycopeptides and effective surveillance measures are required to reduce nosocomial VSEF/VREf spread and to avoid the rise of unusual and misleading VREf genotypes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Lavender is an evergreen shrub native to Northern Africa and other mountainous Mediterranean regions. It grows throughout Southern Europe, the United States, and Australia. Lavender essential oil has been used since ancient times and is known for its anti-inflammatory, antidepressant, antiseptic, antifungal and antimicrobial properties., Methodology: in this study, the antimicrobial activity of two Lavender essential oils (Lavanda sumian and Lavanda grosso) against 16 multidrug-resistant P. aeruginosa strains from clinical ocular samples taken from migrant patients has been investigated. The in vitro cytotoxic activity on human Wong-Kilbourne derivative (WKD) conjunctiva cells from healthy patients and nitric oxide synthase (NOS) activity on murine macrophage (J774.1A) were also evaluated., Results: L. sumian showed lower antimicrobial activity when compared to L. grosso. Both lavender oils tested had no cytotoxic effect at very low concentrations, mostly L. grosso. The essential oils extracted from L. sumian and L. grosso significantly reduced NOS in a cell model., Conclusion: Increase in drug resistance and lack of new antibiotics may encourage the development of natural antimicrobial treatments.

Amphiphilic chitosans have been recently proposed to improve delivery of poorly soluble drugs. In the present paper a derivative obtained by ionic interaction between chitosan and oleic acid was for the first time studied to physically stabilize o/w nanoemulsions of an antimicrobial essential oil, Cymbopogon citratus (Lemongrass), in a low energy and mild conditions emulsification process. The novel combination of spontaneous emulsification process with chitosan oleate amphiphilic properties resulted in a stable dispersion of a few hundred nanometer droplets. Positive zeta potential confirmed the presence of a chitosan shell around the oil droplets, which is responsible for the nanoemulsion physical stabilization and for the maintenance of chitosan bioactive properties, such as mucoadhesion. Cytotoxicity test was performed on four different cell lines (HEp-2, Caco-2, WKD and McCoy cells) showing biocompatibility of the system. The maintenance and in some cases even a clear improvement in the essential oil antimicrobial activity towards nine bacterial and ten fungal strains, all of clinical relevance was verified for Lemongrass nanoemulsion., (Copyright © 2017. Published by Elsevier B.V.)