Molecular epidemiology and nitrofurantoin resistance determinants of nitrofurantoin-non-susceptible Escherichia coli isolated from urinary tract infections

Objectives: The worldwide emergence of multidrug-resistant uropathogens has resulted in the revival of old antibiotics such as nitrofurantoin (NIT) for the treatment of uncomplicated urinary tract infections (UTIs). This study aimed to identify determinants of NIT resistance and to investigate the genetic diversity of NIT-resistant (NIT-R) Escherichia coli isolates. Methods: Six NIT-R and three NIT-susceptible clinical E. coli isolates from patients with UTI were studied. The susceptibility of the isolates to various classes of antibiotics was evaluated by disk diffusion. The presence of plasmid-encoded efflux pump genes (oqxA and oqxB) was investigated by PCR. Nucleotide sequences of the nfsA, nfsB and ribE genes were determined. The genetic relatedness of the NIT-R isolates was evaluated by multilocus sequence typing (MLST). Results: All six NIT-R isolates were characterised with high-level NIT resistance (MIC � 512 mg/L) and they belonged to five distinct STs including ST131 (n = 2), ST73, ST405, ST10 and ST354 (n = 1 each). Amikacin, carbapenems, minocycline, tigecycline and fosfomycin were the most active agents against the studied uropathogens. The oqxA and oqxB genes were not detected in any isolate. All NIT-R isolates harboured inactivating genetic alterations in nfsA and nfsB NfsA H11Y, S33N, S38Y, W212R substitutions, �g638 (frameshift), �a64-g73 (frameshift) and NfsB F84S, P45S, W94Stop, E197Stop substitutions, �nfsB locus. The ribE gene of most isolates was unaffected, except for one isolate co-harbouring a deleterious RibE G85C substitution and NfsA/B alterations. Conclusion: NIT resistance in the studied E. coli isolates was mainly mediated by nfsA and nfsB alterations. © 201

Computed tomography and magnetic resonance imaging of hydatid disease: A pictorial review of uncommon imaging presentations

Hydatid disease (HD), also known as echinococcal disease or echinococcosis, is a worldwide zoonosis with a wide geographic distribution. It can be found in almost all parts of the body and usually remains silent for a long period of time. Clinical history can be varied based on the location, size, host immune response, and complications. The most common imaging modalities used for diagnosis and further evaluations of HD are ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI). Although conventional radiography may be the first used tool, rarely can lead to a definite judgment. Clinical indications and cyst location may alter the choice of imaging. MRI and CT would be useful when the involved area is inaccessible for ultrasound or surgical treatment is required. CT is particularly valuable for osseous organ involvements and the presence of calcifications in the cyst and also demonstrates the size, number, and local complications. MRI can differentiate HD from neoplasms in cases with an unusual appearance on imaging. Moreover, it is preferable in biliary or neural involvements. Besides, more detailed images of MRI and CT could help to resolve the diagnostic uncertainty. Imaging is the main stem for HD diagnosis. Brain, orbit, muscle, bone, and vascular structures are less commonly involved areas. Familiarity with typical clinical presentation, CT scan and MR imaging findings of HD in this sites facilitate the radiologic diagnosis and guiding appropriate treatment. © 2021 The Author(s

Alterations in Mesenteric Lymph Node T Cell Phenotype and Cytokine Secretion are Associated with Changes in Thymocyte Phenotype after LP-BM5 Retrovirus Infection

In this study, mouse MLN cells and thymocytes from advanced stages of LP-BM5 retrovirus infection were studied. A decrease in the percentage of IL-7+ cells and an increase in the percentage of IL-16+ cells in the MLN indicated that secretion of these cytokines was also altered after LP-BM5 infection. The percentage of MLN T cells expressing IL-7 receptors was significantly reduced, while the percentage of MLN T cells expressing TNFR-p75 and of B cells expressing TNFR-p55 increased. Simultaneous analysis of surface markers and cytokine secretion was done in an attempt to understand whether the deregulation of IFN-Υ secretion could be ascribed to a defined cell phenotype, concluding that all T cell subsets studied increased IFN-Υ secretion after retrovirus infection. Finally, thymocyte phenotype was further analyzed trying to correlate changes in thymocyte phenotype with MLN cell phenotype. The results indicated that the increase in single positive either CD4+CD8- or CD4- CD8+ cells was due to accumulation of both immature (CD3- ) and mature (CD3+) single positive thymocytes. Moreover, single positive mature thymocytes presented a phenotype similar to the phenotype previously seen on MLN T cells. In summary, we can conclude that LP-BM5 uses the immune system to reach the thymus where it interferes with the generation of functionally mature T cells, favoring the development of T cells with an abnormal phenotype. These new T cells are activated to secrete several cytokines that in turn will favor retrovirus replication and inhibit any attempt of the immune system to control infection

Microbe-host interplay in atopic dermatitis and psoriasis

Despite recent advances in understanding microbial diversity in skin homeostasis, the relevance of microbial dysbiosis in inflammatory disease is poorly understood. Here we perform a comparative analysis of skin microbial communities coupled to global patterns of cutaneous gene expression in patients with atopic dermatitis or psoriasis. The skin microbiota is analysed by 16S amplicon or whole genome sequencing and the skin transcriptome by microarrays, followed by integration of the data layers. We find that atopic dermatitis and psoriasis can be classified by distinct microbes, which differ from healthy volunteers microbiome composition. Atopic dermatitis is dominated by a single microbe (Staphylococcus aureus), and associated with a disease relevant host transcriptomic signature enriched for skin barrier function, tryptophan metabolism and immune activation. In contrast, psoriasis is characterized by co-occurring communities of microbes with weak associations with disease related gene expression. Our work provides a basis for biomarker discovery and targeted therapies in skin dysbiosis.Peer reviewe

Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021

Background Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. Methods We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. Findings We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5–14 years, 6·29% (5·05 to 7·70) in those aged 15–49 years, 5·72% (4·02 to 7·39) in those aged 50–69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5–14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15–49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50–69 years, and a 3·29% (–5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (–713 to 2180) fewer deaths. Interpretation Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups

Buckling of cracked micro- and nanocantilevers

The size-dependent buckling problem of cracked micro- and nanocantilevers, which have many applications as sensors and actuators, is studied by the stress-driven nonlocal theory of elasticity and Bernoulli-Euler beam model. The presence of the crack is modeled by assuming that the sections at the left and right sides of the crack are connected by a rotational spring. The compliance of the spring, which relates the slope discontinuity and the bending moment at the cracked cross section, is related to the crack length using the method of energy consideration and the theory of fracture mechanics. The buckling equations of the left and right sections are solved separately, and the variationally consistent and constitutive boundary and continuity conditions are imposed to close the problem. Novel insightful results are presented about the effects of the crack length and location, and the nonlocality on the critical loads and mode shapes, also for higher modes of buckling. The results of the present model converge to those of the intact nanocantilevers when the crack length goes to zero and to those of the large-scale cracked cantilever beams when the nonlocal parameter vanishes

Nonlocal strain and stress gradient elasticity of Timoshenko nano-beams with loading discontinuities

A unified approach is applied for determining both strain- and stress-driven differential formulations of Timoshenko nano-beams in presence of loading discontinuities. The consequent models can simulate small scale effects with different types of constitutive laws (such as pure nonlocal, mixture of local and nonlocal phases, and nonlocal gradient). A specific novel feature of the proposed models is the ability to consider loading discontinuities, i.e. points of discontinuities for generalized internal forces occurring in presence of external supports, forces, or couples concentrated at internal points of the nano-beam. To this end, novel constitutive continuity conditions (CCCs) are imposed at the beam interior points of loading discontinuities. CCCs contain integral convolutions of generalized forces or displacements over suitable parts of the nano-beam; they represent a valid alternative to Dirac delta function and are different from the well-known constitutive boundary conditions (CBCs) imposed at the end-points of the nano-beam. Finally, the proposed models are applied for finding closed-form solutions to cases of practical interest

Nonlocal layerwise formulation for bending of multilayered/functionally graded nanobeams featuring weak bonding

The size-dependent bending of perfectly/imperfectly bonded multilayered/stepwise functionally graded nanobeams, e.g. multiwalled carbon nanotubes with weak van der Waals forces, with any arbitrary numbers of layers, exhibiting different material, geometrical, and length-scale properties, is studied through a layerwise formulation of the stress-driven nonlocal theory of elasticity and the Bernoulli-Euler beam theory. The formulation is also valid for the continuously graded nanobeams, where the through-the-thickness material gradation with any arbitrary distribution is approximated in a stepwise manner through many layers. The size-dependency of each layer is accounted for through nonlocal constitutive relationships, which define the strains at each point as the output of integral convolutions in terms of the stresses in all the points of the layer and a kernel. Linear elastic uncoupled interfacial laws are implemented to model the mechanical response of the interfaces. The size-dependent system of equilibrium equations governing the deformations of the layers are derived and subjected to the variationally consistent edge boundary conditions and the constitutive boundary conditions associated with the stress-driven integral convolution. The formulation is applied to multilayered and sandwich nanobeams and the effects of the interfacial imperfections on the displacement fields and the interfacial displacement jumps are studied. It is found that the interfacial imperfections have greater impact on the field variables of multilayered nanobeams than that of the multilayered beams with the large-scale dimensions

Free transverse vibrations of nanobeams with multiple cracks

A nonlocal model is formulated to study the size-dependent free transverse vibrations of nanobeams with arbitrary numbers of cracks. The effect of the crack is modeled by introducing discontinuities in the slope and transverse displacement at the cracked cross-section, proportional to the bending moment and the shear force transmitted through it. The local compliance of each crack is related to its stress intensity factors assuming that the crack tip stress field is undisturbed (non-interacting cracks).The kinematic field is defined based on the Bernoulli-Euler beam theory, and the small-scale size effect is taken into account by employing the constitutive equation of the stress-driven nonlocal theory of elasticity. In this manner, the curvature at each cross-section is defined as an integral convolution in terms of the bending moments at all the cross-sections and a kernel function which depends on a material characteristic length parameter. The integral form of the nonlocal constitutive equation is elaborated and converted into a differential equation subjected to a set of mathematically consistent boundary and continuity conditions at the nanobeam's ends and the cracked cross-sections. The equation of motion in each segment of the nanobeam between cracks is solved separately and the variationally consistent and constitutive boundary and continuity conditions are imposed to determine the natural frequencies. The model is applied to nanobeams with different boundary conditions and the natural frequencies and the mode shapes are presented at the presence of one to four cracks. The results of the model converge to the experimental results available in the literature for the local cracked beams and to the solutions of the intact nanobeams when the crack length goes to zero. The effects of the crack location, crack length, and nonlocality on the natural frequencies are investigated, also for the higher modes of vibrations. Novel findings including the amplification and shielding effects of the cracks on the natural frequencies are presented and discussed