Dogs as carriers of virulent and resistant genotypes of Clostridioides difficile.

While previous research on zoonotic transmission of community-acquired Clostridioides difficile infection (CA-CDI) focused on food-producing animals, the present study aimed to investigate whether dogs are carriers of resistant and/or virulent C. difficile strains. Rectal swabs were collected from 323 dogs and 38 C. difficile isolates (11.8%) were obtained. Isolates were characterized by antimicrobial susceptibility testing, whole-genome sequencing (WGS) and a DNA hybridization assay. Multilocus sequence typing (MLST), core genome MLST (cgMLST) and screening for virulence and antimicrobial resistance genes were performed based on WGS. Minimum inhibitory concentrations for erythromycin, clindamycin, tetracycline, vancomycin and metronidazole were determined by E-test. Out of 38 C. difficile isolates, 28 (73.7%) carried genes for toxins. The majority of isolates belonged to MLST sequence types (STs) of clade I and one to clade V. Several isolates belonged to STs previously associated with human CA-CDI. However, cgMLST showed low genetic relatedness between the isolates of this study and C. difficile strains isolated from humans in Austria for which genome sequences were publicly available. Four isolates (10.5%) displayed resistance to three of the tested antimicrobial agents. Isolates exhibited resistance to erythromycin, clindamycin, tetracycline and metronidazole. These phenotypic resistances were supported by the presence of the resistance genes erm(B), cfr(C) and tet(M). All isolates were susceptible to vancomycin. Our results indicate that dogs may carry virulent and antimicrobial-resistant C. difficile strains.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

[Anatomical description of the anterior hip approach: safety and effect for total arthroplasty]. / Descripción anatómica del abordaje anterior de cadera: seguridad y efecto para artroplastía total.

INTRODUCTION: The anterior hip approach was described since 1881, since then several studies have been conducted that have shown significant advantages over the posterior and lateral direct approaches of the hip. MATERIAL AND METHOD: We conducted a descriptive study with continuous non-probabilistic cases at the Institute of Forensic Sciences from October 2015 to July 2017. Anatomy and distances were described to the neurovascular bundles. Correlation of Spearmans Pearson and Rho was performed. RESULTS: 22 dissections were made, the Femorocutaneous Nerve was identified in 9 specimens, the average lateral Femorocutaneous Nerve distance at Smith-Petersen interval was 11.4 mm, We identified the Ascending Lateral Circumflex artery under the femoral rectum towards the central region of the approach, the separators could be placed around the coxofemoral joint without injuring vital structures, the riskier separator we place it in the anterior wall of the acetabulum, below the Psoasyland with an average distance 28.25 mm to the femoral package. The older you go, the longer the neurovascular bundles were located p 0.05. CONCLUSIONS: High level of safety of the previous approach for hip replacement, distances to vital structures have a reasonable margin, hip replacement offers adequate joint exposure, direct acetabulum vision and atraumatic surgical dissection.

INTRODUCCIÓN: El abordaje anterior de cadera fue descrito en 1881, desde entonces se han realizado diversos estudios que han demostrado ventajas significativas frente a los abordajes posterior y lateral directo de cadera. MATERIAL Y MÉTODO: Se llevó a cabo un estudio descriptivo con casos continuos no probabilísticos en el Instituto de Ciencias Forenses de Octubre de 2015 a Julio de 2017. Se describió anatomía y distancias a los paquetes vasculonerviosos. Se realizó correlación de Pearson y Rho de Spearman. RESULTADOS: Se efectuaron 22 disecciones, el nervio femorocutáneo fue identificado en nueve especímenes, la distancia promedio del nervio femorocutáneo lateral al intervalo de Smith-Petersen fue 11.4 mm, se identificó la arteria circunfleja lateral ascendente debajo del recto femoral hacia la región central del abordaje, se colocaron los separadores alrededor de la articulación coxofemoral sin lesionar estructuras vitales, el separador más riesgoso se ubicó en la pared anterior del acetábulo, debajo del músculo iliopsoas con distancia promedio de 28.25 mm al paquete femoral. A mayor edad mayor distancia a los paquetes neurovasculares p 0.05. CONCLUSIONES: Alto nivel de seguridad del abordaje anterior para artroplastía de cadera, las distancias a estructuras vitales presentan un margen razonable, en artroplastía de cadera ofrece adecuada exposición de la articulación, visión directa del acetábulo y disección quirúrgica atraumática.

The mobile dso-gene-sso element in rolling-circle plasmids of staphylococci reflects the evolutionary history of its resistance gene.

The qacC and lnuA genes of Staphylococcus species were recently proposed to comprise a mobile element when residing on rolling-circle plasmids. Here we present other examples of resistance genes on staphylococcal rolling-circle plasmids, including fosB producing resistance to fosfomycin, cat resulting in resistance to chloramphenicol and cadB for resistance to the toxic heavy metal cadmium. For three of these genes (qacC, lnuA and fosB), evidence was obtained that the genes have spread between different plasmid backgrounds. The lack of mutations in qacC suggests that the spread occurred relatively recently, while the build up of mutations in lnuA and fosB suggests their mobilization occurred in the more distant past. These observations can be explained by the use of the respective antibiotics over time. However, the cat and cadB genes sequences analysed had not collected any mutations, an observation that is not completely understood but possible explanations are discussed. SIGNIFICANCE AND IMPACT OF THE STUDY: We have analysed five resistance genes in Staphylococcus aureus that are positioned between the replication elements of rolling-circle plasmids. For three of these genes, evidence was obtained indicative of recent mobilization. The historical use of the antibiotics to which the genes produce resistance could be related to the number of mutations collected in these genes. However, two other resistance genes have not collected any mutations over time, and the reasons for this are discussed. The analyses presented provide insights into the spread and evolution of antibiotic resistance genes.

Molecular characterization and antimicrobial resistance of STEC strains isolated from healthy cattle in 2011 and 2013 in Spain.

Prevention of Shiga toxin-producing Escherichia coli (STEC) foodborne outbreaks is hampered by its complex epidemiology. We assessed the distribution of virulence genes (VGs), main serogroups/serotypes for public health [haemolytic uraemic syndrome (HUS)-related], antimicrobial resistance (AMR) profiles and pulsed-field gel electrophoresis (PFGE) patterns in a collection of STEC isolates obtained from cattle hide (n = 149) and faecal (n = 406) samples collected during a national survey conducted in Spain in 2011 and 2013. Isolates were cultured using McConkey and CT-SMAC agar after enrichment, and confirmed as STEC by PCR. STEC prevalence in hides (15·4%) was higher than in faeces (10·7%) and O157:H7 was more frequent in the former (2·7% vs. 0·99%). Non-O157 HUS-related serogroups were present albeit at low frequencies. The non-O157 isolates were more heterogeneous than O157:H7 in their VG patterns, with 25/64 presenting VGs from both STEC and enterotoxigenic pathotypes (hybrid isolates). Of the STEC isolates, 62·5% were resistant at least to one antimicrobial, and no differences in AMR between O157:H7 and non-O157 were detected. All isolates had different profiles by PFGE and did not form a cluster. Overall, our results demonstrated that STEC in the cattle reservoir is still a matter of concern for human health due to the presence of HUS-related serogroups, the occurrence of certain VGs, AMR and the additional risks that hybrid isolates may pose, and thus warrants further investigation.

Assessment of virulence factors characteristic of human Escherichia coli pathotypes and antimicrobial resistance in O157:H7 and non-O157:H7 isolates from livestock in Spain.

The distribution of virulence factors (VFs) typical of diarrheagenic Escherichia coli and the antimicrobial resistance (AMR) profiles were assessed in 780 isolates from healthy pigs, broilers, and cattle from Spain. VF distribution was broader than expected, although at low prevalence for most genes, with AMR being linked mainly to host species.

Effect of x-ray energy dispersion in digital subtraction imaging at the iodine K-edge--a Monte Carlo study.

The effect of the energy dispersion of a quasi-monochromatic x-ray beam on the performance of a dual-energy x-ray imaging system is studied by means of Monte Carlo simulations using MCNPX (Monte Carlo N-Particle eXtended) version 2.6.0. In particular, the case of subtraction imaging at the iodine K-edge, suitable for angiographic imaging application, is investigated. The average energies of the two beams bracketing the iodine K-edge are set to the values of 31.2 and 35.6 keV corresponding to the ones obtained with a compact source based on a conventional x-ray tube and a mosaic crystal monochromator. The energy dispersion of the two beams is varied between 0 and 10 keV of full width at half-maximum (FWHM). The signal and signal-to-noise ratio produced in the simulated images by iodine-filled cavities (simulating patient vessels) drilled in a PMMA phantom are studied as a function of the x-ray energy dispersion. The obtained results show that, for the considered energy separation of 4.4 keV, no dramatic deterioration of the image quality is observed with increasing x-ray energy dispersion up to a FWHM of about 2.35 keV. The case of different beam energies is also investigated by means of fast simulations of the phantom absorption.

Contrast cancellation technique applied to digital x-ray imaging using silicon strip detectors.

Dual-energy mammographic imaging experimental tests have been performed using a compact dichromatic imaging system based on a conventional x-ray tube, a mosaic crystal, and a 384-strip silicon detector equipped with full-custom electronics with single photon counting capability. For simulating mammal tissue, a three-component phantom, made of Plexiglass, polyethylene, and water, has been used. Images have been collected with three different pairs of x-ray energies: 16-32 keV, 18-36 keV, and 20-40 keV. A Monte Carlo simulation of the experiment has also been carried out using the MCNP-4C transport code. The Alvarez-Macovski algorithm has been applied both to experimental and simulated data to remove the contrast between two of the phantom materials so as to enhance the visibility of the third one.

[Variability of medical practice in sinusitis as a function of resource utilization]. / Variabilidad de la práctica médica ante una sinusitis en función del consumo de recursos.

OBJECTIVE: To find what factors linked to the doctor affect the variability of clinical practice. DESIGN: Cross-sectional descriptive study through a clinical interview with a fictitious complaint (sinusitis). SETTING: Asturias health centres. PARTICIPANTS: 132 doctors chosen through conglomerate sampling. MEASUREMENTS AND MAIN-RESULTS: Social and professional variables of the doctor (sex, age, years in practice, postgraduate training, courses, recycling courses and distance to the referral centre) were gathered. After the case was presented, the doctor's actions were noted and the cost in pesetas of each action was noted. Cost and the consumption of resources were related to the personal variables of the doctors through multivariate analysis. Mean total expenditure was 76,592 pesetas (minimum: 8958; maximum: 244,220), of which 55,550 were for short-term time off work (average of ten days off) and 15,261 for the consultations made. Average cost of treatment was 3762 pesetas. Through multiple linear regression, the only variable that showed significant effect on expenditure was distance to the referral centre (the greater the distance, the less expenditure). On transforming the total expenditure variable into a dichotomous variable (above and below the mean), the variables with significant effect on less expenditure were courses done, greater distance from the referral centre and being a woman. CONCLUSIONS: There is a very broad variability in decision-taking before the same clinical problem. The only variables that explain (and only partially) an expenditure trend are sex, distance to the referral centre and doing courses.

beta-Amyloid precursor protein (beta APP) in human gut with special reference to the enteric nervous system.

The distribution of the beta-amyloid precursor protein (betaAPP) in the human gastrointestinal tract, from esophagus trough rectum, was studied using immunoblotting, as well as combined immunohistochemical and image analysis (optic microdensitometry) techniques. The study was focused on the enteric nervous system. betaAPP was detected by means of a monoclonal antibody (22C11), which recognizes all betaAPP isoforms as well as betaAPP-like proteins. Immunoblotting revealed two main protein bands, one corresponding to full-length betaAPPs (estimated molecular masses of approximately 97-115 kDa); the other corresponded to a protein with estimated molecular masses of 55 kDa. Specific betaAPP immunoreactivity (IR) was found in the submucous and myenteric plexuses localized in the supporting glial cells rather than in neurons. Differences were encountered neither in the localization nor in the intensity of immunostaining among different segments of the gastrointestinal tract. Moreover, no age-dependent changes were found. betaAPP IR was also regularly observed in blood vessels, primarily labelling endothelial cells. Our results provide evidence for the occurrence of betaAPP in human gastrointestinal tract of healthy people in both neuronal and nonneuronal tissues. Whether or not these findings have functional or clinical relevance remains to be clarified in future studies.

Immunoreactivity for beta/A4 protein, but not for its precursor, in human chromaffin cells.

The present study was designed to establish a) whether chromaffin cells of the human adrenal medulla express immunoreactivity for beta-amyloid precursor protein (beta APP) and/or beta-amyloid protein (beta/A4); and b) whether cells expressing one or both of the above-mentioned proteins display immunoreactivity for the low- (gp75) and/or the high-affinity (gp140-trkA) nerve growth factor receptor. To identify chromaffin cells and their supporting cells, chromogranin A, neurofilament proteins, and S-100 protein were studied in parallel. Beta APP and beta/A4 immunoreactivity (IR) was observed primarily labeling two different cell populations, without colocalization: Beta APP IR was found in the adrenal cortical cells, which were mainly localized in the reticulate layer and in the blood vessel walls, whereas beta/A4 IR was observed in the chromaffin cells. Furthermore, supporting cells were also immunoreactive for beta/A4, and sympathetic ganglionic cells were immunoreactive for both beta APP and beta/A4. Interestingly, clusters of cells expressing beta/A4 IR also displayed gp 75 IR and/or gp140-trkA IR. Finally, all chromaffin cells (identified by chromogranin A IR) were immunolabeled for the 200 kDa neurofilament subunit, but not for a phosphorylated epitope of this protein. These results demonstrate the occurrence of beta/A4 IR, but not of beta APP, in the chromaffin cells of the human adrenal gland. The complementary distribution of amyloid-related proteins, and the possible involvement of neurotrophins in beta/A4 metabolism are discussed.

Expression of beta-amyloid precursor protein (APP) in human dorsal root ganglia.

The present study reports the occurrence and localization of beta-amyloid precursor protein (APP) immunoreactivity (IR) in human lumbar dorsal root ganglia of healthy adult subjects (age range 25-43 years). To ascertain that ganglionic cells displayed APP IR, neurofilament (NFP) and S-100 proteins (S100P) were studied in parallel. Immunoblotting revealed four or five major proteins with apparent molecular masses between 100-125 kDa, which corresponded with the different full-length APP isoforms. Moreover, an additional protein of approximately 55 kDa was detected. Selective APP IR was observed restricted to the satellite glial cell cytoplasms whereas neuron cell bodies resulted unlabeled. Moreover, some intraganglionic nerve fibers also displayed APP IR, apparently labelling Schwann cells. No individual differences among subjects were observed neither in the pattern of APP IR distribution, nor in the intensity of APP IR. Although it remains to be demonstrated whether or not human primary sensory neurons express APP, present results strongly suggest that supporting glial cells may be a primary source of APP or any related peptide, at least in adult healthy people. The functional and clinical relevance of these findings, if any, remain to be clarified.

beta-Amyloid precursor protein (APP)-like immunoreactivity in the human sympathetic ganglia.

The localization of the beta/A4 amyloid precursor protein (APP) was studied in the human lumbar paravertebral sympathetic ganglia of subjects of different ages, free of neurologic disease, using combined immunohistochemistry and image analysis techniques (optic microdensitometry). To ascertain which cells displayed APP-like immunoreactivity (APP-LI), S-100 and neurofilament proteins were studied in parallel to label the supporting glial cells and the neuron perikarya, respectively. Specific APP-LI was observed labelling both neuron cell bodies and supporting glial cells independently of age. In all cases, the intensity of immunostaining was stronger in glial cells than in neurons. Moreover, the intensity of APP-LI was independent of both age and neuron size. Present results provide evidence for the presence of APP-LI in the human sympathetic ganglia, and for the absence of changes in the expression of this protein, or proteins, with aging. The functional and clinical relevance of these findings remains to be clarified.

Effect of denervation on lamellar cells of Meissner-like sensory corpuscles of the rat. An immunohistochemical study.

The denervation-induced changes on S-100 protein, glial fibrillary acidic protein (GFAP) and vimentin immunoreactivity (IR) of the lamellar cells from cutaneous Meissner-like sensory nerve formations (SNF), or corpuscles, of the adult rat hind limb foot-pads were studied, using combined immunohistochemical and image analysis (optic microdensitometry) techniques. Animals were allowed to survive for 1, 3 and 7 days following sciatic and saphenous nerves transection. Lamellar cells of Meissner-like corpuscles displayed S-100 protein- and vimentin-IR, but not GFAP-IR. Denervation caused a marked time-dependent decrease of S-100 protein IR whereas vimentin-IR did not change or weakly increased. No positive GFAP-IR was observed in denervated SNF. These findings suggest that continuity of SNF with nerve fibers supplying them is necessary to maintain some of the immunohistochemical characteristics of the non-neuronal cells of SNF.