Phenotypic and genotypic characterization of oxacillin-susceptible and mecA positive Staphylococcus aureus strains isolated in Uruguay.

The aim of this study was to characterize phenotypically and genotypically 27 mecA positive Staphylococcus aureus strains with oxacillin MICs of ≤2µg/ml by Vitek 2, isolated in different regions of Uruguay. Susceptibility to oxacillin and cefoxitin was studied by gradient diffusion, disk diffusion to cefoxitin, and Phoenix and MicroScan systems. PBP2a was determined. SCCmec typing was performed and the isolates were compared by PFGE. Twenty-six isolates were susceptible to oxacillin; one strain was susceptible to cefoxitin by disk diffusion and 3 strains by gradient diffusion. Phoenix and MicroScan panels detected methicillin resistance in 25 and 27 strains, respectively. Twenty-six strains tested positive for PBP2a. Twenty-six strains carried SCCmec V and 24 belonged to pulsotype A. One strain carried SCCmec IV and did not belong to pulsotype A. Cefoxitin disk diffusion test and PBP2a detection correctly identified 26 of these 27 strains as MRSA. PFGE results suggest the dissemination of a cluster of MRSA carrying SCCmec V.

A Virtual Instrument for Measuring the Piezoelectric Coefficients of a Thin Disc in Radial Resonant Mode.

In this paper, we describe and present a Virtual Instrument, a tool that allows the determination of the electromechanical, dielectric, and elastic coefficients in polarised ferroelectric ceramic discs (piezoceramics) in the linear range, including all of the losses when the piezoceramics are vibrating in radial mode. There is no evidence in the recent scientific literature of any automatic system conceived and implemented as a Virtual Instrument based on an iterative algorithm issued as an alternative to solve the limitations of the ANSI IEEE 176 standard for the characterisation of piezoelectric coefficients of thin discs in resonant mode. The characterisation of these coefficients is needed for the design of ultrasonic sensors and generators. In 1995, two of the authors of this work, together with other authors, published an iterative procedure that allowed for the automatic determination of the complex constants for lossy piezoelectric materials in radial mode. As described in this work, the procedures involved in using a Virtual Instrument have been improved: the response time for the characterisation of a piezoelectric sample is shorter (approximately 5 s); the accuracy in measurement and, therefore, in the estimates of the coefficients has been increased; the calculation speed has been increased; an intuitive, simple, and friendly user interface has been designed, and tools have been provided for exporting and inspecting the measured and processed data. No Virtual Instrument has been found in the recent scientific literature that has improved on the iterative procedure designed in 1995. This Virtual Instrument is based on the measurement of a unique magnitude, the electrical admittance (Y = G + iB) in the frequency range of interest. After measuring the electrical admittance, estimates of the set of piezoelectric coefficients of the device are obtained. The programming language used in the construction of the Virtual Instrument is LabVIEW 2019®.

Systematic Analysis of FASTK Gene Family Alterations in Cancer.

The FASTK family of proteins have been recently reported to play a key role in the post-transcriptional regulation of mitochondrial gene expression, including mRNA stability and translation. Accumulated studies have provided evidence that the expression of some FASTK genes is altered in certain types of cancer, in agreement with the central role of mitochondria in cancer development. Here, we obtained a pan-cancer overview of the genomic and transcriptomic alterations of FASTK genes. FASTK, FASTKD1, FASTKD3 and FASTKD5 showed the highest rates of genetic alterations. FASTK and FASTKD3 alterations consisted mainly of amplifications that were seen in more than 8% of ovarian and lung cancers, respectively. FASTKD1 and FASTKD5 were the most frequently mutated FASTK genes, and the mutations were identified in 5-7% of uterine cancers, as well as in 4% of melanomas. Our results also showed that the mRNA levels of all FASTK members were strongly upregulated in esophageal, stomach, liver and lung cancers. Finally, the protein-protein interaction network for FASTK proteins uncovers the interaction of FASTK, FASTKD2, FASTKD4 and FASTKD5 with cancer signaling pathways. These results serve as a starting point for future research into the potential of the FASTK family members as diagnostic and therapeutic targets for certain types of cancer.

Role of POLE and POLD1 in familial cancer.

PURPOSE: Germline pathogenic variants in the exonuclease domain (ED) of polymerases POLE and POLD1 predispose to adenomatous polyps, colorectal cancer (CRC), endometrial tumors, and other malignancies, and exhibit increased mutation rate and highly specific associated mutational signatures. The tumor spectrum and prevalence of POLE and POLD1 variants in hereditary cancer are evaluated in this study. METHODS: POLE and POLD1 were sequenced in 2813 unrelated probands referred for genetic counseling (2309 hereditary cancer patients subjected to a multigene panel, and 504 patients selected based on phenotypic characteristics). Cosegregation and case-control studies, yeast-based functional assays, and tumor mutational analyses were performed for variant interpretation. RESULTS: Twelve ED missense variants, 6 loss-of-function, and 23 outside-ED predicted-deleterious missense variants, all with population allele frequencies <1%, were identified. One ED variant (POLE p.Met294Arg) was classified as likely pathogenic, four as likely benign, and seven as variants of unknown significance. The most commonly associated tumor types were colorectal, endometrial and ovarian cancers. Loss-of-function and outside-ED variants are likely not pathogenic for this syndrome. CONCLUSIONS: Polymerase proofreading-associated syndrome constitutes 0.1-0.4% of familial cancer cases, reaching 0.3-0.7% when only CRC and polyposis are considered. ED variant interpretation is challenging and should include multiple pieces of evidence.

Macrolide-lincosamide-streptogramin B resistance phenotypes and their associated genotypes in Staphylococcus aureus isolates from a tertiary level public hospital of Uruguay.

This study was undertaken to investigate the resistance phenotypes to macrolide-lincosamide-streptogramin B (MLSB) antibiotics and their associated genotypes in isolates of Staphylococcus aureus. We analyzed one hundred, consecutive, non-duplicate isolates (methicillin-susceptible MSSA, n=53 and methicillin-resistant MRSA, n=47) obtained from various clinical samples between July 2012 to December 2013. The resistance profile to MLSB antibiotics was determined by phenotypic methods and the resistance genes were detected by PCR assays. All of the isolates were subjected to pulsed-field gel electrophoresis (SmaI-PFGE). The overall prevalence of resistance to MLSB antibiotics was 38% and the resistance phenotype distribution was as follows: cMLSB, 22%; iMLSB, 10%; MSB, 5% and L, 1%. We detected ermA, ermC, ermB and mrsA/B genes in these resistant isolates. The single ermA gene was commonly observed mainly in those with a cMLSB R phenotype, whereas the combination ermA and ermC was more commonly observed in isolates with inducible expression. The patterns of SmaI-PFGE suggest a great genetic diversity in both MRSA and MSSA resistant to MLSB antibiotics. The results demonstrate the local presence of S. aureus resistant to MLSB antibiotics and its most frequently described responsible genes. Some of these isolates, especially those with the iMLSB phenotype, may be associated with therapeutic failure. Therefore, efforts should be directed to the correct detection of all MLSB resistant isolates using appropriate laboratory tests. PFGE results reveal a wide spread of resistance genes rather than the circulation of S. aureus clones resistant to MLSB antibiotics.

Dynamic remodeling of histone modifications in response to osmotic stress in Saccharomyces cerevisiae.

BACKGROUND: Specific histone modifications play important roles in chromatin functions; i.e., activation or repression of gene transcription. This participation must occur as a dynamic process. Nevertheless, most of the histone modification maps reported to date provide only static pictures that link certain modifications with active or silenced states. This study, however, focuses on the global histone modification variation that occurs in response to the transcriptional reprogramming produced by a physiological perturbation in yeast. RESULTS: We did a genome-wide chromatin immunoprecipitation analysis for eight specific histone modifications before and after saline stress. The most striking change was rapid acetylation loss in lysines 9 and 14 of H3 and in lysine 8 of H4, associated with gene repression. The genes activated by saline stress increased the acetylation levels at these same sites, but this acetylation process was quantitatively minor if compared to that of the deacetylation of repressed genes. The changes in the tri-methylation of lysines 4, 36 and 79 of H3 and the di-methylation of lysine 79 of H3 were slighter than those of acetylation. Furthermore, we produced new genome-wide maps for seven histone modifications, and we analyzed, for the first time in S. cerevisiae, the genome-wide profile of acetylation of lysine 8 of H4. CONCLUSIONS: This research reveals that the short-term changes observed in the post-stress methylation of histones are much more moderate than those of acetylation, and that the dynamics of the acetylation state of histones during activation or repression of transcription is a much quicker process than methylation.

Detection of Vancomycin Resistance among Methicillin-Resistant Staphylococcus aureus Strains Recovered from Children with Invasive Diseases in a Reference Pediatric Hospital.

Vancomycin is the cornerstone in treating methicillin-resistant Staphylococcus aureus (MRSA) infections. However, therapeutic failures can occur when MRSA strains with decreased susceptibility to glycopeptides (DSG) are involved. The aim of this study was to detect and characterize DSG in MRSA recovered from children with invasive diseases at a reference pediatric hospital between 2009 and 2019. Fifty-two MRSA strains were screened using agar plates with vancomycin 3 and 4 mg/L (BHI-3 and BHI-4); the VITEK2 system; and standard and macro E-tests. Suspicious hVISA were studied by population analysis profiling-area under the curve (PAP-AUC), and wall thickness was analyzed by transmission electron microscopy. Neither VRSA nor VISA were detected in this set. As only three strains met the hVISA criteria, the PAP-AUC study included 12 additional MRSA strains that grew one colony on BHI-4 plates or showed minimum inhibitory concentrations of vancomycin and/or teicoplanin ≥ 1.5 mg/L. One strain was confirmed as hVISA by PAP-AUC. The wall thickness was greater than the vancomycin-susceptible control strain; it belonged to ST30 and carried SCCmec IV. As expected, a low frequency of hVISA was found (1.9%). The only hVISA confirmed by PAP-AUC was not detected by the screening methods, highlighting the challenge that its detection represents for microbiology laboratories.

Ferroelectric, Dielectric and Electromechanical Performance of Ba0.92Ca0.08Ti0.95Zr0.05O3 Ceramics with an Enhanced Curie Temperature.

Ba0.92Ca0.08Ti0.95Zr0.05O3 (BCZT8-5) ceramic materials have been scarcely studied as lead-free piezo/ferroelectrics despite their enhanced Curie temperature (>100 °C) with respect to most studied BCZT compositions. In this work, homogeneous dense BCZT8-5 ceramics with grain size in the range of 20 µm, and optimum ferroelectric, dielectric, and electromechanical performance, were prepared by the mixed oxides route using moderate synthesis (1250 °C-2 h) and sintering (1400 °C-2 h) conditions. Thickness-poled thin disks and monomodal shear plate resonators were used for the determination of piezoelectric coefficients, coupling factors, elastic, and dielectric permittivity coefficients, including all losses, by iterative analysis of impedance curves at resonance. Furthermore, the thermal evolution of the piezoelectric characteristics at resonance was determined to assess the enhanced working range of the ceramics (≈100 °C). Ferroelectric hysteresis loops and strains vs. electric-field butterfly loops were also measured and showed soft behavior with Ec = 2 kV/cm, Pr = 12 µC/cm2 after a maximum applied field of 3 kV was used. The ceramics showed a high endurance of P-E cycles to electrical fatigue up to 107 cycles. Moreover, dielectric properties as a function of temperature were also accomplished and showed nearly normal ferroelectric behavior, characteristic of samples with low crystallographic disorder. Overall, these ceramics showed high sensitivity and higher stability than other currently studied BCZT compositions.

Solid State Processing of BCZT Piezoceramics Using Ultra Low Synthesis and Sintering Temperatures.

Lead-free (Ba0.92Ca0.08) (Ti0.95 Zr0.05) O3 (BCZT) ceramics were prepared by a solid-state route (SSR) using ultra-low synthesis (700 °C/30 min and 700 °C/2 h) and sintering temperatures (from 1150 °C to 1280 °C), due to prior activation and homogenization by attrition milling of the starting high purity raw materials for 6 h before the synthesis and of the calcined powders for 3 h before the sintering. The comparison of the thermal analysis of the mixture of the starting raw materials and the same mixture after 6 h attrition milling allowed to evidence the mechanisms of activation, resulting in a significant decrease of the perovskite formation temperature (from 854 °C down to 582 °C). The secondary phases that limit the functional properties of the ceramic and their evolution with the sintering conditions were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM), which allowed the design of a two-step sintering method to eliminate them. A pure tetragonal BCZT perovskite phase (P4mm, c/a = 1.004) and homogeneous ceramic microstructure was obtained for synthesis at 700 °C for 2 h and sintering with the use of a two-step sintering treatment (900 °C for 3 h and 1280 °C for 6 h). The best electromechanical properties achieved were d33 = 455 pC/N, kp = 35%, Qm = 155.

Recommendations for the classification of germline variants in the exonuclease domain of POLE and POLD1.

BACKGROUND: Germline variants affecting the proofreading activity of polymerases epsilon and delta cause a hereditary cancer and adenomatous polyposis syndrome characterized by tumors with a high mutational burden and a specific mutational spectrum. In addition to the implementation of multiple pieces of evidence for the classification of gene variants, POLE and POLD1 variant classification is particularly challenging given that non-disruptive variants affecting the proofreading activity of the corresponding polymerase are the ones associated with cancer. In response to an evident need in the field, we have developed gene-specific variant classification recommendations, based on the ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology) criteria, for the assessment of non-disruptive variants located in the sequence coding for the exonuclease domain of the polymerases. METHODS: A training set of 23 variants considered pathogenic or benign was used to define the usability and strength of the ACMG/AMP criteria. Population frequencies, computational predictions, co-segregation data, phenotypic and tumor data, and functional results, among other features, were considered. RESULTS: Gene-specific variant classification recommendations for non-disruptive variants located in the exonuclease domain of POLE and POLD1 were defined. The resulting recommendations were applied to 128 exonuclease domain variants reported in the literature and/or public databases. A total of 17 variants were classified as pathogenic or likely pathogenic, and 17 as benign or likely benign. CONCLUSIONS: Our recommendations, with room for improvement in the coming years as more information become available on carrier families, tumor molecular characteristics and functional assays, are intended to serve the clinical and scientific communities and help improve diagnostic performance, avoiding variant misclassifications.

Brain radiotoxicity-related 15CAcBRT gene expression signature predicts survival prognosis of glioblastoma patients.

BACKGROUND: Glioblastoma is the most common and devastating primary brain cancer. Radiotherapy is standard of care; however, it is associated with brain radiation toxicity (BRT). This study used a multi-omics approach to determine whether BRT-related genes (RGs) harbor survival prognostic value and whether their encoded proteins represent novel therapeutic targets for glioblastoma. METHODS: RGs were identified through analysis of single-nucleotide variants associated with BRT (R-SNVs). Functional relationships between RGs were established using Protein-Protein Interaction networks. The influence of RGs and their functional groups on glioblastoma prognosis was evaluated using clinical samples from the Glioblastoma Bio-Discovery Portal database and validated using the Chinese Glioma Genome Atlas dataset. The identification of clusters of radiotoxic and putative pathogenic variants in proteins encoded by RGs was achieved by computational 3D structural analysis. RESULTS: We identified the BRT-related 15CAcBRT molecular signature with prognostic value in glioblastoma, by analysis of the COMT and APOE protein functional groups. Its external validation confirmed clinical relevance independent of age, MGMT promoter methylation status, and IDH mutation status. Interestingly, the genes IL6, APOE, and MAOB documented significant gene expression levels alteration, useful for drug repositioning. Biological networks associated with 15CAcBRT signature involved pathways relevant to cancer and neurodegenerative diseases. Analysis of 3D clusters of radiotoxic and putative pathogenic variants in proteins coded by RGs unveiled potential novel therapeutic targets in neuro-oncology. CONCLUSIONS: 15CAcBRT is a BRT-related molecular signature with prognostic significance for glioblastoma patients and represents a hub for drug repositioning and development of novel therapies.

[Epidemiological and clinical characteristics of children with COVID-19 cared for in a private health provider in Uruguay]. / Características epidemiológicas y clínicas de los niños con COVID-19 asistidos en un prestador de salud privado de Uruguay.

BACKGROUND: After the detection of the first cases of SARS-CoV-2 and the declaration of a health emergency in the country, community transmission of the virus remained low to moderate until November 2020, later becoming medium and high. Children under 15 years of age constitute the least affected group. The diagnosis is confirmed by RT-qPCR. The usefulness of the CT (cycle threshold) is discussed. AIM: To describe the epidemiological and clinical characteristics of children infected with SARS-CoV-2 and the relationship between the CT value and clinical presentation. METHOD: A descriptive, retrospective study was carried out in patients under 16 years of age with SARS-CoV-2 infection, assisted by a health provider in Montevideo between epidemiological week (EW) 3 of2020 and EW 9 of2021. Clinical variables, epidemiological notion, severity and evolution were described. The CT value at diagnosis was recorded and compared with the presence of symptoms. RESULTS: Patients under 16 years of age represented 16.6% of the total infected (794 in 4,792). 70% of the cases occurred between the months of January and February 2021. 67.6% presented intradomiciliary contact. The mean age was 7.5 ± 4.1 years, 51% were male. 55% presented symptoms and 45% were asymptomatic; no significant differences were observed in the mean, mode and age range of both groups. None presented comorbidities. In the group of 440 symptomatic patients, 55% presented fever: 32% associated with other symptoms, mainly upper respiratory symptoms, and 23% as the only symptom. The CT value was obtained in 536 of the 794 patients (67.5%). The mean CT was 29.7+5.8 in the symptomatic group vs. 31.5 ± 5.7 in asymptomatic patients (p > 0.05). Three patients were hospitalized, none required intensive care and none died. CONCLUSIONS: The prevalence and incidence of SARS-CoV-2 infection in children accompany that of adults and the majority had mild or asymptomatic forms, without complications. In this series, the CT value was not different in symptomatic and asymptomatic children. Close household contact was the main source of infection.

Solving the enigma of POLD1 p.V295M as a potential cause of increased cancer risk.

Germline variants that affect the proofreading activity of polymerases epsilon (POLE) and delta (POLD1) predispose to colorectal adenomas and carcinomas, among other cancers. All cancer-associated pathogenic variants reported to date consist of non-disruptive genetic changes affecting the sequence that codifies the exonuclease domain (ED). Generally, disruptive (frameshift, stop-gain) POLE and POLD1 variants and missense variants outside the ED do not predispose to cancer. However, this statement may not be true for some, very specific variants that would indirectly affect the proofreading activity of the corresponding polymerase. We evaluated, by using multiple approaches, the possibility that POLD1 c.883G>A; p.(Val295Met), -a variant located 9 amino acids upstream the ED and present in ~0.25% of hereditary cancer patients-, affects POLD1 proofreading activity. Our findings show cumulative evidence that support no alteration of the proofreading activity and lack of association with cancer. The variant is classified as likely benign according to the ACMG/AMP guidelines.

[Actinomyces sp. brain abscess: a rare infection in children. A case report]. / Absceso cerebral por Actinomyces sp.: una infección infrecuente en niños. A propósito de un caso.

Despite advances in diagnostic and treatment techniques, intracranial infections remain serious diseases with an estimated incidence of between 0.3 and 1.3 cases/100,000 inhabitants. We present a previously healthy patient with an intraoperative diagnostic of brain abscess, in whom although the culture showed polymicrobial development, Actinomyces sp was presumptively identified in the pathological anatomy. Given this finding, prolonged combined antibiotic therapy was performed with good evolution. Absceso cerebral por Actinomyces sp.: una infección infrecuente en niños. A propósito de un caso Actinomyces sp. brain abscess: a rare infection in children. A case report The presentation of this suppurative process was nonspecific and the contribution of the anatomopathology in the etiological diagnosis was relevant. The identification of an unusual microorganism defined the need to deepen the identification of predisposing factors.

A pesar de los avances en las técnicas de diagnóstico y tratamiento, las infecciones intracraneanas son aún enfermedades graves con una incidencia estimada entre 0,3 y 1,3 casos por cada 100 000 habitantes. Se presenta un paciente previamente sano con un absceso cerebral de diagnóstico intraoperatorio en quien, si bien el cultivo evidenció desarrollo polimicrobiano, se identificó presuntivamente Actinomyces sp. en la anatomía patológica. Dado este hallazgo, se realizó antibioticoterapia combinada prolongada con buena evolución. La presentación de este proceso supurado fue inespecífica y la contribución de la anatomía patológica en el diagnóstico etiológico fue relevante. La identificación de un microorganismo inhabitual definió la necesidad de profundizar en la determinación de factores predisponentes.

Determination of the PIC700 Ceramic's Complex Piezo-Dielectric and Elastic Matrices from Manageable Aspect Ratio Resonators.

Achieving good piezoelectric properties, such as the widely reported d33 charge coefficient, is a good starting point in establishing the potential applicability of piezoceramics. However, piezoceramics are only completely characterized by consistent piezoelectric-elastic-dielectric material coefficient matrices in complex form, i.e., including all losses. These matrices, which define the various alternative forms of the constitutive equations of piezoelectricity, are required for reliable virtual prototyping in the design of new devices. To meet this need, ten precise and accurate piezoelectric dielectric and elastic coefficients of the material, including all losses, must be determined for each alternative. Due to the difficulties arising from the coupling of modes when using the resonance method, this complete set of parameters is scarcely reported. Bi0.5Na0.5TiO3-based solid solutions are already commercially available in Europe and Japan. Here, we report a case study of the determination of these sets of material coefficients (diα, giα, eiα and hiα; sE,Dαß and cE,Dαß; εTik and εSik; and ßTik and ßSik), including all losses, of the commercial PIC700 eco-piezoceramic. Plate, disk, and cylinder ceramic resonators of a manageable aspect ratio were used to obtain all the material coefficients. The validation procedure of the matrices is also given by FEA modeling of the considered resonators.

Cyclic Mechanical Fatigue Lifetime of Bi0.5Na0.5TiO3-Based Eco-Piezoceramics.

The mechanical strength and cyclic fatigue behavior of PIC700 commercial eco-piezoceramic disks are investigated under biaxial loading on unpoled and poled samples. The bending strength of unpoled samples was higher than those of poled ones. Fatigue tests were conducted under a load ratio of 10 at a frequency of 20 Hz with a sinusoidal waveform. The curve fitting for the S-N fatigue diagram is used to predict the lifetime of these eco-piezoceramics and describe their fatigue behavior. It was also found that the unpoled samples exhibited higher fatigue resistance than the poled ones. The fatigue limit of maximum load for ten million cycles of unpoled and poled samples was estimated to be 160 and 135 MPa, respectively. The detailed observations of the fatigue fracture surfaces by scanning electron microscopy (SEM) indicated that a wavy surface with a mixture of transgranular and intergranular fractures occurred preferentially in the case of the poled material. On the other hand, transgranular fractures seem to be predominant in the unpoled samples. It appears that the poling process causes the change in failure characteristics due to domain orientation that leaves an anisotropic stress field in the material. The poled ceramics possess a local stress concentration created by the orientation under the electric poling field of the 90° ferroelectric-ferroelastic domains. Under this local stress concentration, a microstructural degeneration is induced by domain switching under the cyclic load that accelerates crack growth, thereby reducing fatigue lifetime.

MgNb2 O6 Modified K0.5 Na0.5 NbO3 Eco-Piezoceramics: Scalable Processing, Structural Distortion and Complex Impedance at Resonance.

In this work, piezoceramics of the lead-free composition K0.5 Na0.5 NbO3 with an increasing amount of MgNb2 O6 (0, 0.5, 1, 2 wt.%) were prepared through conventional solid-state synthesis and sintered in air atmosphere at 1100 °C. The effect of magnesium niobate addition on structure, microstructure and piezoelectric properties was evaluated. The ceramics maintain the orthorhombic Amm2 phase for all compositions, while an orthorhombic Pbcm secondary phase was found for increasing the concentration of MgNb2 O6 . Our results show that densification of these ceramics can be significantly improved up to 94.9 % of theoretical density by adding a small amount of magnesium-based oxide (1 wt.%). Scanning electron microscopy morphology of the 1 wt.% system reveals a well-packed structure with homogeneous grain size of ∼2.72 µm. Dielectric and piezoelectric properties become optimal for 0.5-1.0 wt.% of MgNb2 O6 that shows, with respect to the unmodified composition, either higher piezoelectric coefficients, lower anisotropy and relatively low piezoelectric losses (d33 =97 pC N-1 ; d31 =-36.99 pC N-1 and g31 =-14.04×10-3  mV N-1 ; Qp (d31 )=76 and Qp (g31 )=69) or enhanced electromechanical coupling factors (kp =29.06 % and k31 =17.25 %).

FEA Study of Shear Mode Decoupling in Nonstandard Thin Plates of a Lead-Free Piezoelectric Ceramic.

The finite-element analysis (FEA) is used in this work to study the impedance curves and modes of motion at resonance of nonstandard shear plates, thickness poled, and longitudinally excited. An ecological, lead-free, piezoelectric ceramic of ( 1-x )(Bi0.5Na0.5)TiO3- x BaTiO3 with x =0.06 (BNBT6) composition is studied. The FEA modeling is based on the full matrix of the material coefficients. These are obtained from complex impedance measurements on two-thickness poled resonators. A study as a function of the variations of the dimensions of the plate was accomplished ( t = thickness for poling and L and w = lateral dimensions, where w is the distance between electrodes for the electrical excitation). We aimed to a further understanding, and, thus, the ability to control, the coupling of the main shear resonance and the lateral modes. The use of uncoupled shear modes to obtain the material parameters is a key issue for their determination as complex quantities, thus considering all material losses, electromechanical, dielectric, and elastic.

A computational and structural analysis of germline and somatic variants affecting the DDR mechanism, and their impact on human diseases.

DNA-Damage Response (DDR) proteins are crucial for maintaining the integrity of the genome by identifying and repairing errors in DNA. Variants affecting their function can have severe consequences since failure to repair damaged DNA can result in cells turning cancerous. Here, we compare germline and somatic variants in DDR genes, specifically looking at their locations in the corresponding three-dimensional (3D) structures, Pfam domains, and protein-protein interaction interfaces. We show that somatic variants in metastatic cases are more likely to be found in Pfam domains and protein interaction interfaces than are pathogenic germline variants or variants of unknown significance (VUS). We also show that there are hotspots in the structures of ATM and BRCA2 proteins where pathogenic germline, and recurrent somatic variants from primary and metastatic tumours, cluster together in 3D. Moreover, in the ATM, BRCA1 and BRCA2 genes from prostate cancer patients, the distributions of germline benign, pathogenic, VUS, and recurrent somatic variants differ across Pfam domains. Together, these results provide a better characterisation of the most recurrent affected regions in DDRs and could help in the understanding of individual susceptibility to tumour development.

Presence of genes encoding enterotoxins in Staphylococcus aureus isolates recovered from food, food establishment surfaces and cases of foodborne diseases.

The aim of this study was to describe the microbiological characteristics and profile of genes encoding enterotoxins in 95 Staphylococcus aureus isolates obtained between April 2011 and December 2014 from foodstuffs, persons and surfaces of retail food stores. After microbiological identification and antimicrobial susceptibility testing, polymerase chain reactions (PCR) were performed, targeting sea, seb, sec, sed and see genes that code for classical enterotoxins (ET) A-E, and three additional genes: seg , seh and sei , coding for so-called "new enterotoxins" G, H and I. The isolates were characterized by Pulsed Field Gel Electrophoresis (PFGE), and five selected isolates were further analyzed through Multi Locus Sequence Typing (MLST). It is noteworthy that 54.7% of the examined isolates harbored one or more of the investigated ET gene types. Most positive isolates carried more than one ET gene up to five types; seg was the most frequent ET gene, followed by sei. Five enterotoxin-coding isolates also coded for some antimicrobial resistance genes. Two of them, and four additional non-enterotoxic isolates carried erm genes expressing inducible clindamycin resistance. PFGE-types were numerous and diverse, even among enterotoxin-coding strains, because most isolates did not belong to known foodborne outbreaks and the sampling period was long. MLST profiles were also varied, and a new ST 3840 was described within this species. ST 88 and ST 72 enterotoxin-coding isolates have been identified in other regions in association with foodborne outbreaks. This manuscript reports the first systematic investigation of enterotoxin genes in S. aureus isolates obtained from foodstuffs and infected people in Uruguay.