Antimicrobial Susceptibility and Characterization of Resistance Mechanisms of Corynebacterium urealyticum Clinical Isolates

Corynebacterium urealyticum is a non-diphtherial urease-producing clinically relevant corynebacterial, most frequently involved in urinary tract infections. Most of the C. urealyticum clinical isolates are frequently resistant to several antibiotics. We investigated the susceptibility of 40 C. urealyticum isolated in our institution during the period 2005-2017 to eight compounds representative of the main clinically relevant classes of antimicrobial agents. Antimicrobial susceptibility was determined by the Epsilometer test. Resistance genes were searched by PCR. All strains were susceptible to vancomycin whereas linezolid and rifampicin also showed good activity (MICs90 = 1 and 0.4 mg/L, respectively). Almost all isolates (39/40, 97.5%) were multidrug resistant. The highest resistance rate was observed for ampicillin (100%), followed by erythromycin (95%) and levofloxacin (95%). Ampicillin resistance was associated with the presence of the blaA gene, encoding a class A ?-lactamase. The two rifampicin-resistant strains showed point mutations driving amino acid replacements in conserved residues of RNA polymerase subunit ? (RpoB). Tetracycline resistance was due to an efflux-mediated mechanism. Thirty-nine PFGE patterns were identified among the 40 C. urealyticum, indicating that they were not clonally related, but producing sporadic infections. These findings raise the need of maintaining surveillance strategies among this multidrug resistant pathogen.This research was funded by Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases (REIPI) D16/0016/0007 and RD16/0016/0008), and co-financed by European Development Regional Fund “A way to achieve Europe”, Operative program Intelligent Growth 2014-2020

The new multi-frequency instrument (MFI2) for the QUIJOTE facility in Tenerife

The QUIJOTE (Q-U-I joint Tenerife) experiment combines the operation of two radio-telescopes and three instruments working in the microwave bands 10?20 GHz, 26-36 GHz and 35-47 GHz at the Teide Observatory, Tenerife, and has already been presented in previous SPIE meetings (Hoyland, R. J. et al, 2012; Rubiño-Martín et al., 2012). The Cosmology group at the IAC have designed a new upgrade to the MFI instrument in the band 10-20 GHz. The aim of the QUIJOTE telescopes is to characterise the polarised emission of the cosmic microwave background (CMB), as well as galactic and extra-galactic sources, at medium and large angular scales. This MFI2 will continue the survey at even higher sensitivity levels. The MFI2 project led by the Instituto de Astrofísica de Canarias (IAC) consists of five polarimeters, three of them operating in the sub-band 10?15 GHz, and two in the sub-band 15-20 GHz. The MFI2 instrument is expected to be a full two-three times more sensitive than the former MFI. The microwave complex correlator design has been replaced by a simple correlator design with a digital back-end based on the latest Xilinx FPGAs (ZCU111). During the first half of 2019 the manufacture of the new cryostat was completed and since then the opto-mechanical components have been designed and manufactured. It is expected that the cryogenic front-end will be completed by the end of 2022 along with the FPGA acquisition and observing system. This digital system has been employed to be more robust against stray ground-based and satellite interference, having a frequency resolution of 1 MHz.The MFI2 instrument is being developed by the Instituto de Astrofisica de Canarias (IAC), with an instrumental participation from the Universidad Politecnica de Cartagena (UPCT). Partial financial support is provided by the Spanish Ministry of Science and Innovation (MICINN), under the projects AYA2017-84185-P, IACA15-BE-3707, EQC2018-004918-P and the FEDER Agreement INSIDE-OOCC (ICTS-2019-03-IAC-12). We also acknowledge financial support of the Severo Ochoa Programs SEV-2015-0548 and CEX2019-000920-S

BBB opening with focused ultrasound in nonhuman primates and Parkinson’s disease patients: Targeted AAV vector delivery and PET imaging

血液脳関門開放術による遺伝子治療法の開発 --身体を傷つけない脳疾患の治療を目指して--. 京都大学プレスリリース. 2023-04-20.Intracerebral vector delivery in nonhuman primates has been a major challenge. We report successful blood-brain barrier opening and focal delivery of adeno-associated virus serotype 9 vectors into brain regions involved in Parkinson’s disease using low-intensity focus ultrasound in adult macaque monkeys. Openings were well tolerated with generally no associated abnormal magnetic resonance imaging signals. Neuronal green fluorescent protein expression was observed specifically in regions with confirmed blood-brain barrier opening. Similar blood-brain barrier openings were safely demonstrated in three patients with Parkinson’s disease. In these patients and in one monkey, blood-brain barrier opening was followed by 18F-Choline uptake in the putamen and midbrain regions based on positron emission tomography. This indicates focal and cellular binding of molecules that otherwise would not enter the brain parenchyma. The less-invasive nature of this methodology could facilitate focal viral vector delivery for gene therapy and might allow early and repeated interventions to treat neurodegenerative disorders

Incidence, risk factors, and outcomes of second neoplasms in patients with acute promyelocytic leukemia:the PETHEMA-PALG experience

The most important challenges in acute promyelocytic leukemia (APL) is preventing early death and reducing long-term events, such as second neoplasms (s-NPLs). We performed a retrospective analysis of 2670 unselected APL patients, treated with PETHEMA “chemotherapy based” and “chemotherapy free” protocols. Only de novo APL patients who achieved complete remission (CR) and completed the three consolidation cycles were enrolled into the analysis. Out of 2670 APL patients, there were 118 (4.4%) who developed s-NPLs with the median latency period (between first CR and diagnosis of s-NPL) of 48.0 months (range 2.8–231.1): 43.3 (range: 2.8–113.9) for s-MDS/AML and 61.7 (range: 7.1–231.1) for solid tumour. The 5-year CI of all s-NPLs was of 4.43% and 10 years of 7.92%. Among s-NPLs, there were 58 cases of s-MDS/AML, 3 cases of other hematological neoplasms, 57 solid tumours and 1 non-identified neoplasm. The most frequent solid tumour was colorectal, lung and breast cancer. Overall, the 2-year OS from diagnosis of s-NPLs was 40.6%, with a median OS of 11.1 months. Multivariate analysis identified age of 35 years (hazard ratio = 0.2584; p &lt; 0.0001) as an independent prognostic factor for s-NPLs. There were no significant differences in CI of s-NPLs at 5 years between chemotherapy-based vs chemotherapy-free regimens (hazard ratio = 1.09; p = 0.932). Larger series with longer follow-up are required to confirm the potential impact of ATO+ATRA regimens to reduce the incidence of s-NPLs after front-line therapy for APL.</p

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Inter-Rater Variability in the Evaluation of Lung Ultrasound in Videos Acquired from COVID-19 Patients

12 páginas, 7 figuras, 1 tablaLung ultrasound (LUS) allows for the detection of a series of manifestations of COVID-19, such as B-lines and consolidations. The objective of this work was to study the inter-rater reliability (IRR) when detecting signs associated with COVID-19 in the LUS, as well as the performance of the test in a longitudinal or transverse orientation. Thirty-three physicians with advanced experience in LUS independently evaluated ultrasound videos previously acquired using the ULTRACOV system on 20 patients with confirmed COVID-19. For each patient, 24 videos of 3 s were acquired (using 12 positions with the probe in longitudinal and transverse orientations). The physicians had no information about the patients or other previous evaluations. The score assigned to each acquisition followed the convention applied in previous studies. A substantial IRR was found in the cases of normal LUS (κ = 0.74), with only a fair IRR for the presence of individual B-lines (κ = 0.36) and for confluent B-lines occupying 50% (κ = 0.50). No statistically significant differences between the longitudinal and transverse scans were found. The IRR for LUS of COVID-19 patients may benefit from more standardized clinical protocols.This research was partially funded by CDTI (Spanish acronym: Centre for Industrial Tech- nological Development), funding number COI-20201153. Partially supported by the Google Cloud Research Credits program with the funding number GCP19980904, by the project RTI2018-099118- A-I00 founded by MCIU/AEI/FEDER UE and by the European Commission–NextGenerationEU, through CSIC’s Global Health Platform (PTI Salud Global)

The new multi-frequency instrument (MFI2) for the QUIJOTE facility in Tenerife

Event: SPIE Astronomical Telescopes + Instrumentation, 2022, Montréal, Québec, Canada.et al.The QUIJOTE (Q-U-I joint Tenerife) experiment combines the operation of two radio-telescopes and three instruments working in the microwave bands 10–20 GHz, 26–36 GHz and 35–47 GHz at the Teide Observatory, Tenerife, and has already been presented in previous SPIE meetings (Hoyland, R. J. et al, 2012; Rubi˜no-Mart´ın et al., 2012). The Cosmology group at the IAC have designed a new upgrade to the MFI instrument in the band 10–20 GHz. The aim of the QUIJOTE telescopes is to characterise the polarised emission of the cosmic microwave background (CMB), as well as galactic and extra-galactic sources, at medium and large angular scales. This MFI2 will continue the survey at even higher sensitivity levels. The MFI2 project led by the Instituto de Astrof´ısica de Canarias (IAC) consists of five polarimeters, three of them operating in the sub-band 10–15 GHz, and two in the sub-band 15–20 GHz. The MFI2 instrument is expected to be a full two–three times more sensitive than the former MFI. The microwave complex correlator design has been replaced by a simple correlator design with a digital back-end based on the latest Xilinx FPGAs (ZCU111). During the first half of 2019 the manufacture of the new cryostat was completed and since then the opto-mechanical components have been designed and manufactured. It is expected that the cryogenic front-end will be completed by the end of 2022 along with the FPGA acquisition and observing system. This digital system has been employed to be more robust against stray ground-based and satellite interference, having a frequency resolution of 1 MHz.Partial financial support is provided by the Spanish Ministry of Science and Innovation (MICINN), under the projects AYA2017-84185-P, IACA15-BE-3707, EQC2018-004918-P and the FEDER Agreement INSIDE-OOCC (ICTS-2019-03-IAC-12). We also acknowledge financial support of the Severo Ochoa Programs SEV-2015-0548 and CEX2019-000920-S.Peer reviewe

Assessment of a New ROS1 Immunohistochemistry Clone (SP384) for the Identification of ROS1 Rearrangements in Patients with Non–Small Cell Lung Carcinoma: the ROSING Study

Introduction: The ROS1 gene rearrangement has become an important biomarker in NSCLC. The College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology testing guidelines support the use of ROS1 immunohistochemistry (IHC) as a screening test, followed by confirmation with fluorescence in situ hybridization (FISH) or a molecular test in all positive results. We have evaluated a novel anti-ROS1 IHC antibody (SP384) in a large multicenter series to obtain real-world data. Methods: A total of 43 ROS1 FISH-positive and 193 ROS1 FISH-negative NSCLC samples were studied. All specimens were screened by using two antibodies (clone D4D6 from Cell Signaling Technology and clone SP384 from Ventana Medical Systems), and the different interpretation criteria were compared with break-apart FISH (Vysis). FISH-positive samples were also analyzed with next-generation sequencing (Oncomine Dx Target Test Panel, Thermo Fisher Scientific). Results: An H-score of 150 or higher or the presence of at least 70% of tumor cells with an intensity of staining of 2+ or higher by the SP384 clone was the optimal cutoff value (both with 93% sensitivity and 100% specificity). The D4D6 clone showed similar results, with an H-score of at least 100 (91% sensitivity and 100% specificity). ROS1 expression in normal lung was more frequent with use of the SP384 clone (p < 0.0001). The ezrin gene (EZR)-ROS1 variant was associated with membranous staining and an isolated green signal FISH pattern (p = 0.001 and p = 0.017, respectively). Conclusions: The new SP384 ROS1 IHC clone showed excellent sensitivity without compromising specificity, so it is another excellent analytical option for the proposed testing algorithm

RICORS2040 : The need for collaborative research in chronic kidney disease

Chronic kidney disease (CKD) is a silent and poorly known killer. The current concept of CKD is relatively young and uptake by the public, physicians and health authorities is not widespread. Physicians still confuse CKD with chronic kidney insufficiency or failure. For the wider public and health authorities, CKD evokes kidney replacement therapy (KRT). In Spain, the prevalence of KRT is 0.13%. Thus health authorities may consider CKD a non-issue: very few persons eventually need KRT and, for those in whom kidneys fail, the problem is 'solved' by dialysis or kidney transplantation. However, KRT is the tip of the iceberg in the burden of CKD. The main burden of CKD is accelerated ageing and premature death. The cut-off points for kidney function and kidney damage indexes that define CKD also mark an increased risk for all-cause premature death. CKD is the most prevalent risk factor for lethal coronavirus disease 2019 (COVID-19) and the factor that most increases the risk of death in COVID-19, after old age. Men and women undergoing KRT still have an annual mortality that is 10- to 100-fold higher than similar-age peers, and life expectancy is shortened by ~40 years for young persons on dialysis and by 15 years for young persons with a functioning kidney graft. CKD is expected to become the fifth greatest global cause of death by 2040 and the second greatest cause of death in Spain before the end of the century, a time when one in four Spaniards will have CKD. However, by 2022, CKD will become the only top-15 global predicted cause of death that is not supported by a dedicated well-funded Centres for Biomedical Research (CIBER) network structure in Spain. Realizing the underestimation of the CKD burden of disease by health authorities, the Decade of the Kidney initiative for 2020-2030 was launched by the American Association of Kidney Patients and the European Kidney Health Alliance. Leading Spanish kidney researchers grouped in the kidney collaborative research network Red de Investigación Renal have now applied for the Redes de Investigación Cooperativa Orientadas a Resultados en Salud (RICORS) call for collaborative research in Spain with the support of the Spanish Society of Nephrology, Federación Nacional de Asociaciones para la Lucha Contra las Enfermedades del Riñón and ONT: RICORS2040 aims to prevent the dire predictions for the global 2040 burden of CKD from becoming true