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Background and purposeSpain has been heavily affected by COVID-19. Reallocation of resources for managing the outbreak might have caused a disruption in stroke care. This study analyses the impact on stroke care of reorganising the healthcare system in response to the first COVID-19 outbreak peak in Spain and the strategies adopted by Spanish stroke units to deal with this impact.Materials and methodsWe obtained data from a structured survey sent to the responsible of stroke units across the country. We recorded the number of strokes, stroke code activations, intravenous thrombolysis treatments and mechanical thrombectomies during February and March 2019 and 2020. We also collected information on the impact on workflow metrics and on the availability of specialised neurological care and rehabilitation treatments, the characteristics of stroke care for patients with SARS-CoV-2 infection and the impact on human resources. We compared the activity data between 2019 and 2020 and the information on activity and impact on stroke care between regions classified according to the disease incidence rate.ResultsFifty-seven (75%) of all stroke units in Spain responded to the survey. There was an overall reduction in admissions for all stroke types during the outbreak’s peak and in the number of stroke code activations and intravenous thrombolysis treatments, results that were independent of the COVID-19 incidence rate. Participants reported a delay in workflow metrics and a reduction of admissions to stroke units, outpatient clinics and rehabilitation therapies. Specific pathways and protocols for managing stroke patients with SARS-CoV-2 infection have been established.ConclusionThe COVID-19 outbreak has jeopardised all phases of stroke care. As a consequence, some patients with stroke did not receive adequate treatment.

The objective of this study was to compare the effects of two warming protocols (three-step vs. one-step dilution) on embryo quality, post-warming embryo survival and embryo cell viability of donkey embryos vitrified by the Cryotop method. Twenty, Day 7-8, grade 1-2 donkey embryos were measured, morphologically evaluated and vitrified using the Cryotop technique. Embryos were then randomly warmed using two different warming procedures: (i) W3 (three-step dilution; n = 11): embryos were warmed in 1 M, 0.5 M and 0 M sucrose, and (ii) W1/0.5 (one-step dilution; n = 9): embryos were warmed directly in 0.5 M sucrose. After 3 and 24 h of warming, the embryos were measured and evaluated for their morphology, developmental stage and viability (Propidium Iodide-Hoechst 33,342 dyes). Although both treatments decreased embryo quality after warming (P 0.05), no significant differences (P 0.05) were observed between protocols in terms of post-warming embryo quality, diameter and embryo survival. Greater percentages of dead cells (P 0.001) were observed when embryos were warmed directly in 0.5 M sucrose (one-step dilution) when compared to the three-step protocol. The percentage of ruptured embryos was 27.3% and 0% in W3 and W1/0.5 protocols (P = 0.0893), respectively. In conclusion, warming Cryotop-vitrified donkey embryos directly in 0.5 M sucrose had no negative effects on embryo quality and post-warming embryo survival. Moreover, one-step protocol may help to prevent rupture when donkey embryos warmed directly in 0.5 M sucrose. These results observed in vitro must be verified by embryo transfer.

Two Arundo donax biological control agents, Tetramesa romana, the arundo wasp, and Rhizaspidiotus donacis, the arundo scale, have been established in Texas, USA and Morelos, Mexico for ten years. A...

Many domestic donkey breeds are at risk of extinction, there is a critical urgency for genome resource banking. In the present study, we examined whether the use of Ficoll 70 added to the vitrification medium containing ethylene glycol (EG), dimethyl sulfoxide (DMSO) and sucrose improves the cryotolerance of donkey in vivo derived embryos. Day 7-8, grade 1-2 donkey embryos were measured and morphologically evaluated and then vitrified-warmed using the Cryotop technique. Before vitrification, embryos were randomly distributed into two groups: (i) VS1 (n = 14): vitrified using 15% EG + 15% DMSO + 0.5 M sucrose; and (ii) VS2 (n = 10): vitrified in the same medium supplemented also with 18% of Ficoll 70. After 24 h of warming, the embryos were measured and evaluated for their morphology, development and viability (Propidium Iodide-Hoechst 33342 dyes). Post-warming survival was numerically higher but not significantly different (P 0.05) when embryos were vitrified in VS2 (70%) compared to VS1 (57.1%). Embryo rupture was only observed in the VS1 group (21.4%, 3/14). Higher embryo diameter was observed in all groups after 24 h culture (P 0.05). No significant differences (P 0.05) were observed among treatments in terms of percentages of cell death. These results demonstrate that the addition of Ficoll 70 to the vitrification medium is not a pre-requisite for successful vitrification of donkey embryos. However, its addition seems to enhance some of the post-warming embryo quality characteristics. Since no statistically significant evidence was found, further studies should be conducted in order to confirm our findings.

The aim of this study was to assess seasonal variations during different periods of the breeding season (spring and summer) on stallion sperm DNA fragmentation and in vivo fertility associated with cooled-stored semen samples. Ejaculates were collected from eleven stallions and assessed for sperm motility (assessed by computer-assisted sperm analysis) and plasma membrane integrity (evaluated under fluorescence microscopy). Sperm DNA fragmentation (evaluated by the Sperm Chromatin Dispersion test) was assessed in cooled-stored semen at 5 °C for up to 24 h. Artificial insemination was performed throughout the breeding season. Mares were inseminated with cooled-stored semen (up to 24 h) every other day until ovulation. Pregnancy rates per cycle were determined detecting the embryonic vesicle by ultrasonography fifteen days after ovulation. Values (mean ± SD) for progressive sperm motility were significantly higher (P 0.05) in spring (53.57 ± 9.97%) in comparison to summer (41.37 ± 10.81%). No significant differences in plasma membrane integrity were found between seasons (P 0.05). Sperm DNA fragmentation was significantly lower (P 0.01) in spring in comparison to summer after 0h (4.81 ± 1.87% vs. 8.77 ± 5.78%), 6h (9.00 ± 3.19% vs. 18.73 ± 8.22%) and 24h (14.6 ± 4.13% vs. 30.14 ± 9.85%) of cooled-storage. Pregnancy rates per cycle were also significantly higher (P 0.01) in spring (50%) in comparison to summer (37%). There was a moderate negative relationship between positive pregnancies and sperm with fragmented DNA (r = - 0.619; P 0.001). Semen samples associated with moderate fertility levels (Pregnancy rate 50%) showed a higher percentage of sperm with fragmented DNA compared to samples obtaining higher fertility levels. In conclusion, seasonal variations were found during the breeding season, obtaining lower sperm DNA fragmentation and higher pregnancy rates in spring. Additionally, samples with the highest proportion of sperm with fragmented DNA showed the lowest fertility levels throughout the breeding season.

There are conflicting data regarding the role of KRAS mutation on the risk of venous thromboembolism (VTE) in colorectal cancer (CRC) patients. Moreover, the role of other biomarkers such as NRAS or BRAF has not been studied. To analyze the incidence of VTE in a cohort of patients with CRC based on KRAS, NRAS, and BRAF status. We performed a retrospective review of patients with unresectable locally advanced and metastatic CRC (mCRC) and known KRAS/NRAS/BRAF status, attended in the Medical Oncology Department of the Hospital General Universitario Gregorio Maranon (Madrid, Spain). The primary outcome was VTE defined as any venous thromboembolic event that occurred either 6 months before or at any time after the diagnosis of CRC. The biomarker status (KRAS, NRAS, and BRAF) and other predictors of thrombosis were collected. One hundred and ninety-four patients were identified and included in the analysis. Forty-one patients (21.1%) experienced VTE. The incidence was 19.1% in RAS-mutated patients, 28.6% in BRAF-mutated patients and 21% in triple wild-type patients (p = NS). In multivariate analysis, ECOG ≥ 2 was the only independent predictor of VTE (OR 8.73; CI 95% 1.32–57.82; p = 0.025). In our study, biomarkers have not been associated with an increased risk of VTE in CRC patients. A high incidence of VTE in BRAF-mutated patients has been observed and should be explored in further studies.

Mirizzi syndrome is a rare complication of chronic calculous cholecystitis. Preoperative diagnosis is challenging due to the absence of pathognomonic signs and symptoms and low sensitivity rates of imaging tests. Historically, laparotomy has been the preferred choice of surgical management. Endoscopic and laparoscopic approaches have been increasingly described as diagnostic and therapeutic options for Mirizzi type I and II, but data is limited regarding the management of more complex cases. We describe a staged endoscopic and laparoscopic approach for the management of type IV Mirizzi syndrome and review the management options.

The agile and power-efficient locomotion of a water strider has inspired many water-walking devices. These bioinspired water strider robots generally adopt a DC motor to create a sculling trajectory of the driving leg. These robots are, thus, inevitably heavy with many supporting legs decreasing the velocity of the robots. There have only been a few attempts to employ smart materials despite their advantages of being lightweight and having high power densities. This paper proposes an artificial muscle-based water-walking robot capable of moving forward and turning with four degrees of freedom. A compliant amplified shape memory alloy actuator (CASA) used to amplify the strain of a shape memory alloy wire enables a wide sculling motion of the actuation leg with only four supporting legs to support the entire weight of the robot. Design parameters to increase the actuation strain of the actuator and to achieve a desired swing angle (80°) are analyzed. Finally, experiments to measure the forward speed and angular velocities of the robot are carried out to compare with other robots. The robot weighs only 0.236 g and has a maximum and average speed of 1.56, 0.31 body length per second and a maximum and average angular velocity of 145.05°/s and 14.72°/s.

A shallow sulcus characterizes trochlear dysplasia (TD) of the femoral trochlea, which can lead to chronic pain or instability of the patellofemoral joint. Breech presentation at birth has been identified as a risk factor for developing this condition, which an ultrasound can identify early. Early treatment could be considered at this stage, given the potential for remodelling in these skeletally immature patients. Newborns with breech presentation at birth who meet the inclusion criteria will be enrolled and randomised in equal proportions between treatment with the Pavlik harness and observation. The primary objective is to determine the difference in the means of the sulcus angle between the two treatment arms at two months. Ours is the first study protocol to evaluate an early non-invasive treatment for TD in the newborn with breech presentation at birth using a Pavlik harness. We hypothesised that trochlear dysplasia could be reverted when identified and treated early in life with a simple harness, as it is done with developmental dysplasia of the hip.

12 pags., 5 figs. -- Supplementary Information is available at https://doi.org/10.26508/lsa. 202101252., Heterodimerization of RNA binding proteins Nrd1 and Nab3 is essential to communicate the RNA recognition in the nascent transcript with the Nrd1 recognition of the Ser5-phosphorylated Rbp1 C-terminal domain in RNA polymerase II. The structure of a Nrd1-Nab3 chimera reveals the basis of heterodimerization, filling a missing gap in knowledge of this system. The free form of the Nrd1 interaction domain of Nab3 (NRID) forms a multi-state three-helix bundle that is clamped in a single conformation upon complex formation with the Nab3 interaction domain of Nrd1 (NAID). The latter domain forms two long helices that wrap around NRID, resulting in an extensive protein-protein interface that would explain the highly favorable free energy of heterodimerization. Mutagenesis of some conserved hydrophobic residues involved in the heterodimerization leads to temperature-sensitive phenotypes, revealing the importance of this interaction in yeast cell fitness. The Nrd1-Nab3 structure resembles the previously reported Rna14/Rna15 heterodimer structure, which is part of the poly(A)-dependent termination pathway, suggesting that both machineries use similar structural solutions despite they share little sequence homology and are potentially evolutionary divergent., NMR experiments were performed in the “Manuel Rico” NMR laboratory (LMR) of the Spanish National Research Council (CSIC), a node of the Spanish Large-Scale National Facility (ICTS R-LRB). Funding was provided by grants: PID2020-112821GB-I00 to JM Pérez-Cañadillas and MÁ Jiménez funded by MCIN/ AEI /10.13039/501100011033/; CTQ2017-84371-P to JM Pérez-Cañadillas and MÁ Jiménez funded by MCIN/ AEI /10.13039/501100011033/ and by “ERDF A way of making Europe”; BFU2017-84694-P to O Calvo funded by MCIN/ AEI /10.13039/501100011033/ and by “ERDF A way of making Europe”; and RED2018-102467-T to O Calvo and JM Pérez-Cañadillas funded by MCIN/ AEI /10.13039/501100011033/. JM Pérez-Cañadillas was also funded by a grant of the Biomedicine program of Community of Madrid (B2017/BMD-3770 RYPSE-CM) that is co-financed with ERDF and ESFESF. The IBFG is supported in part by an institutional grant from the “Junta de Castilla y León” (Programa “Escalera de Excelencia” de la Junta de Castilla y León, Ref. CLU-2017-03 co-funded by O.P. ERDF from Castilla y León 14-20).

Peru celebrates 200 years of independence in 2021. Over this period of independent life, and despite the turbulent socio-political scenarios, from internal armed conflict to economic crisis to political instability over the last 40 years, Peru has experienced major changes on its epidemiological and population health profile. Major advancements in maternal and child health as well as in communicable diseases have been achieved in recent decades, and today Peru faces an increasing burden of non-communicable diseases including mental health conditions. In terms of the configuration of the public health system, Peru has also strived to secure country-wide optimal health care, struggling in particular to improve primary health care and intercultural services. The science and technology infrastructure has also evolved, although the need for substantial investments remains if advancing science is to be a national priority. Climate change will also bring significant challenges to population health given Peru's geographical and microclimates diversity. Looking back over the 200-years of independence, we present a summary of key advances in selected health-related fields, thus serving as the basis for reflections on pending agendas and future challenges, in order to look forward to ensuring the future health and wellbeing of the Peruvian population. Resumen (translated abstract): El Perú cumple 200 años de independencia en 2021. Durante estos dos siglos de vida independiente, junto con periodos sociales y políticos turbulentos, incluyendo un conflicto armado interno, hiperinflación y la inestabilidad política de los últimos 40 años, el Perú ha experimentado importantes cambios en su perfil epidemiológico con repercusiones directas en la salud de la población. En las últimas décadas, los indicadores de salud materno-infantil y de las enfermedades transmisibles muestran mejoría importante, pero el país se enfrenta de manera simultánea a una carga cada vez mayor de enfermedades no transmisibles y de salud mental. En cuanto a los sistemas de salud pública, se han realizado esfuerzos por aumentar la cobertura y calidad de la atención de salud en todo el país, apostándose en particular por mejorar la atención primaria. La ciencia y tecnología relacionadas con la salud también han mejorado, aunque si se quiere que la ciencia sea una prioridad nacional, son necesarias inversiones sustanciales. El cambio climático traerá importantes desafíos para la salud de la población, dada la diversidad geográfica y de microclimas del país. Para conmemorar los 200 años de vida independiente del Perú, presentamos un resumen de avances clave en diversas áreas y temas relacionados con la salud. Este repaso sirve como base para reflexionar sobre agendas y desafíos pendientes y futuros, con el fin de asegurar la salud y el bienestar de la población peruana en las próximas décadas. El Perú cumple 200 años de independencia en 2021. Durante estos dos siglos de vida independiente, junto con periodos sociales y políticos turbulentos, incluyendo un conflicto armado interno, hiperinflación y la inestabilidad política de los últimos 40 años, el Perú ha experimentado importantes cambios en su perfil epidemiológico con repercusiones directas en la salud de la población. En las últimas décadas, los indicadores de salud materno-infantil y de las enfermedades transmisibles muestran mejoría importante, pero el país se enfrenta de manera simultánea a una carga cada vez mayor de enfermedades no transmisibles y de salud mental. En cuanto a los sistemas de salud pública, se han realizado esfuerzos por aumentar la cobertura y calidad de la atención de salud en todo el país, apostándose en particular por mejorar la atención primaria. La ciencia y tecnología relacionadas con la salud también han mejorado, aunque si se quiere que la ciencia sea una prioridad nacional, son necesarias inversiones sustanciales. El cambio climático traerá importantes desafíos para la salud de la población, dada la diversidad geográfica y de microclimas del país. Para conmemorar los 200 años de vida independiente del Perú, presentamos un resumen de avances clave en diversas áreas y temas relacionados con la salud. Este repaso sirve como base para reflexionar sobre agendas y desafíos pendientes y futuros, con el fin de asegurar la salud y el bienestar de la población peruana en las próximas décadas

Background The usefulness of therapeutic drug monitoring(TDM) of infliximab during induction and its relationship with clinical outcome in patients with inflammatory bowel disease(IBD) is well established. However, the optimal time of monitoring in terms of clinical outcomes remains unclear. The aim is to evaluate the TDM at various times during induction and its association with clinical remission. Methods An observational, retrospective and single-centre study of patients with active disease ,Crohn’s disease (CD) or ulcerative colitis(UC), was performed. Induction treatment with infliximab 0, 2, 6 weeks was conducted and if there was response, maintenance therapy was provided. Antibody levels were measured in serum samples at week 2 and week 14 by using an enzyme-linked immunosorbent assay, within the therapeutic range(3-8 µg/ml). Patients were followed at least for one year or until loss of response. The clinical response was assessed in week 14 and week 52 by Harvey-Bradshaw Index in CD and Mayo Partial Index in UC. Results Out of 93 patients that were evaluated, 23 with UC(24.73%) and 70 with CD(75.27%,), 65 (69.89%) and 58 patients(62.37%) achieved remission at week 14 and week 52 respectively. Infliximab levels at week 14 but not at week 2 were significantly higher in patients who achieved clinical remission in both week 14 (5.8 vs 2.1 µg/ml; p=0.0002) as in week 52 (6.4 vs 1.9 µg/ml; p=0.0001). The levels at week 14, but not at week 2 had predictive value of remission, in both week 14 [OR 1,4 (CI 1.14-1.76) p=0.001] and week 52 [OR 1.4 (CI 1.15-1.87); p=0.001]. The patients with immunosuppressants at week 14 presented the highest rate of remission in week 52 (77.78 vs 52.63; p=0.014). The intensification of treatment was a negative factor to achieve remission both in week 14 and at week 52. Conclusion The levels of infliximab in week 14 are higher and have predictive value of clinical remission both in early (week 14) and long-term (week 52). Levels of infliximab in week 2 did not provide significant predictive value of clinical response. The use of immunosuppressants could be a favourable factor of clinical outcome.

Introduction: Racial and ethnic disparities exist in three areas related to hematopoietic cell transplantation (HCT): donor availability, access, and post-HCT outcomes. A significant barrier to access to HCT for patients (pts) of racial or ethnic minorities (REM) is the limited availability of fully matched donors (i.e., grafts matched at HLA-A, -B, -C, and -DRB1 loci) in volunteer registries. While mismatched unrelated donor (MMUD) grafts (i.e., 0.9). There were no differences in one-year OS (77% vs 74%, p = 0.9) and EFS (63% vs 72%, p = >0.9) between NHW and REM pts. Similarly, rates of acute (17% vs 13%, p = 0.5) and chronic GVHD (5.7% vs 11%, p = 0.5) were comparable between NHW and REM pts. Conclusion: PTCy resulted in encouraging clinical outcomes following MMUD HCT. Post-HCT OS, RFS, and GVHD rates were comparable between NHW and REM pts and those receiving 7/8 or highly mismatched grafts. Favorable post-HCT outcomes following MMUD with PTCy may increase HCT utilization and access for REM pts. Citation Format: Antonio M. Jimenez Jimenez, Sunil Iyer, Krishna Komanduri, Samantha Brown, Trent Wang, Stephanie Chinapen, Denise Pereira, Sean Devlin, Mark Goodman, Amer Beitinjaneh, Craig Sauter, Lazaros Lekakis, Miguel Angel Perales, Doris Ponce, Brian Shaffer. HLA-mismatched unrelated donor hematopoietic cell transplantation with post-transplant cyclophosphamide improves clinical outcomes for racial and ethnic minority patients with hematologic malignancies [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr B121.

This work has been partially financed by the projects PGC2018-097988-A-I00, PID2020-116097RB-I00, and UAL2020-SEJ-D1784 funded by FEDER/Ministry of Science and Innovation (MCI) of Spain-State Research Agency (AEI) and P20_00094 funded by Andalusia Government., Science inquiry and modeling activities have been proved to heighten emotional situations; therefore, research about emotions should aim to identify which activities promote student engagement with Science, Technology, Engineering and Mathematics fields through multidimensional models that include emotional and cognitive engagement. This research is focused on science teachers’ need to carefully review their classroom instructions to ensure that students are provided with opportunities to develop appropriate understandings of acid/base models (and their concepts). To achieve this, we have implemented a short model-based inquiry acid-base instructional sequence in the context of a TV-spot about chewing gum. A descriptive, non-experimental quantitative methodology with a heuristic (emotional: self-report questionnaire; and cognitive: self-regulation questionnaire) has been used to analyze what Pre-Service Secondary Education Teachers from several Spanish universities recognize to have learned and felt in each activity. Differences regarding knowledge declared by the participants were identified in all the tasks from before to after carrying them out. Furthermore, the results seem to indicate that there are significant relationships between the knowledge and the emotions, being different depending on the skill involved. Significant correlations between emotions have been found. However, there were no significant correlations with either rejection and knowledge or with other emotions, which points to emotional engagement. Generally, no significant differences were identified between emotions and gender or universities, with some exceptions between genders in two tasks. Thus, the results led us to reflect on the instructional sequence implementation’s ability to bring awareness to the learning process and how it produces multidimensional engagements., FEDER/Ministry of Science and Innovation (MCI) of Spain-State Research Agency (AEI) PGC2018-097988-A-I00 PID2020-116097RB-I00 UAL2020-SEJ-D1784, Andalusia Government P20_00094

Transcatheter Aortic valve Replacement (TAVR) has emerged as paradigm shift in the treatment of patients with severe symptomatic aortic stenosis. Clinical and performance data on long-term TAVR are still limited. The aim of this study was to determine the survival and the factors predicting mortality after TAVR with the first and second generation of prostheses. Methods From April 2008 to December 2019, the auto-expandible prostheses were implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk. The first generation prostheses included CoreValve and Accutrak System and the second prostheses included Evolut R and Pro. Results The mean age was 79.4±6.6 years. The logistic EuroSCORE and STS score were 17.1±11% and 5.7±3.9%, respectively. The implantation success rate was 98.87%. In-hospital mortality was 3.7%, and the combined endpoint of death, vascular complications, myocardial infarction or stroke had a rate of 15.1%. The clinical outcomes in according to prosthesis generation were, for pacemaker requirement (CoreValve vs. Accutrak system vs. Evolut R vs. and Evolut pro) 35.3% vs. 26.1% vs. 14.3% vs. 14%, p=0.001; and the paravalvular aortic regurgitation, were: none 28% vs. 44.8% vs. 43.3% vs. 58; mild 40% vs. 32.3% vs. 30.8% vs. 35.2%; moderate 32% vs. 20.3 vs. 23.9% vs. 5.7%; severe 0% vs. 2.6% vs. 0% vs. 1.1, p 0.001 The late mortality (beyond 30 days) was 35.9%. Survival at 1, 3, 5, 7 and 9 years were 88.9%, 76.1%, 61.1%, 44% and 32.6% respectively, after a mean follow-up of 42.3±27 months. The NYHA functional class improved from 3.1±0.6 to 1.77±0.7 in the follow-up. At 5 years, 5 patients had severe prosthetic valve dysfunction (severe stenosis and moderate transvalvular regurgitation The predictors of cumulative mortality were: Charlson index [HR 1.25 (95% CI 1.077–1.461), p=0.004], Readmision Heart Failure [HR 3.02 (95% CI 1.554–5.879), p=0.001], stroke post-TAVR [HR 3.472 (95% CI 1.115–10.53), p=0.032], residual aortic regurgitation [HR 1.45 (95% CI 1.093–1.934), p=0,010], and severe pulmonary hypertension [HR −0.983 (95% CI 0.645–0.423) p=0.032]. Conclusions TAVR is associated with significant survival benefit throughout 3.09 years of follow-up. Survival during follow-up depends particularly among patients with associated comorbidities and cardiac markers such as aortic regurgitation or pulmonary hypertension Funding Acknowledgement Type of funding sources: None.

The durability of transcatheter heart valves and long-term clinical outcomes are unknown. The aim of this study was to evaluate clinical and hemodynamic outcomes 10 years after Transcatheter Aortic Valve Implantation (TAVI). Methods Between April 2008 and December 2011, 230 patients underwent TAVI for the treatment of severe symptomatic aortic stenosis with the auto-expandable prosthesis. Results The mean age, logistic EuroSCORE and STS score were 79.3±6.4 years, 19.8±13% and 6.8±5% respectively. Mean aortic valve gradient decreased from 49.8±15 mm Hg to 8.6±3.8 mmHg after TAVI, to 11.1±9 mm Hg at 5 years, and 25.7±12 mmHg at 7 years (p for post-TAVI trend 0.03). Mean aortic valve area increased from 0.63±0.16 cm2 to 1.57±0.3cm2 after TAVI to 1.48±0.2 at 5 years and 0.87±0.3 cm2 at 7 years (p for post-TAVI trend 0.01). Mean left ventricular ejection fraction increased from 61.1±15% to 65.5±11% after TAVI, to 58.2±17% at 5 years and 57.2±8% at 7 years (p for post-TAVI trend 0.001). The total mortality after a mean of 53±34 months was 73% and 34.4% was cardiovascular mortality. Survival rates at 1 to 10 years were at 86%, 75.4%, 64.9%, 59.6%, 52.6%, 33.1%, 24.9%, 20.7%, 10.4% and 10.4% respectively. Only 4 patients had severe prosthetic valve dysfunction (severe stenosis and moderate-severe transvalvular regurgitation). Median survival time after TAVI was 6 years (95% confidence interval [CI]: 5.89 to 6.28), and the risk of death was significantly increased in patients with frailty (adjusted hazard ratio [HR]: 1.874; 95% CI: 1.028 to 3.418), p=0.040, Charlson index [HR=1.212 (95% CI: 1.094–1.341), p Conclusions In our center, the transcatheter aortic valve implantation in patients at high surgical risk, presented favourable clinical outcomes and hemodynamic performance after ten years of follow-up. Funding Acknowledgement Type of funding sources: None.

Acute Kidney Injury (AKI) after cardiac surgery is associated with increased mortality, but very few data exist on the occurrence of AKI associated with Transcatheter Aortic Valve Replacement (TAVR). The aim of this study was to determine the frequency and prognosis of AKI after transcatheter aortic valve replacement. Methods Between April 2008 and December 2019, 751 patients with severe aortic stenosis underwent to TAVR. The AKI was defined according to Valve set by the Academic Research Consortium, as the absolute increase in serum creatinine ≥0.3 mg/dl at 72 hours a percutaneous procedure. Results AKI was identified in 127 patients (16.9%) and 3 patients required renal replacement therapy. After implantation there was a slight improvement in renal function, baseline serum creatinine decreased from 1.37±0.9mg/dl to 1.22±0.6 mg/dl, p=0.01 and glomerular filtration rate (GFR) increased from 49.7±20 to 53.9±22, p In patients with AKI, the mortality at 30 days was 12.6% compared to 1.3% of patients without AKI, [OR=11.08 (95% CI 4.631–26.514) p In the multivariate analysis AKI was an independent predictor of cumulative total mortality [HR=1.644 (95% CI 1.230–2.198), p=0.001] and threatening bleeding [HR=3.623 (95% CI 1.448–8.764), p=0.004], but not cardiovascular mortality [HR=1.496 (95% CI 0,834.2.682), p=0.177]; readmission by heart failure [HR=1.249 (95% CI 0.652–2.392), p=0.502], myocardial infarction [HR=1.929 (95% CI 0.705–5.287), p=0.201]; or stroke [HR=1.662 (95% CI 0.874–3.142), p=0.118]. The predictors of AKI were: general anesthesia [HR=2.112 (1.038–4.246), p=0.039]; the first generation aortic prostheses [HR=3.485 (95% CI 2.211–5.442), p=0.001]; tricuspid regurgitation [HR=1.604 (95% CI 1.057–2.435), p=0.026] and renal chronic failure [HR=2.060 95% CI 1.148–3.699); p=0.015]. Conclusions Deterioration of renal function in patients undergoing TAVR is a serious and frequent complication. The occurrence of AKI was associated with increase early mortality and also was a predictor of worse outcomes throughout 3.65±2 years of follow-up. Funding Acknowledgement Type of funding sources: None.

Background Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac condition, is mainly caused by pathogenic variants in sarcomeric genes. Alpha tropomyosin gene (TPM1) account for a small percentage (1–5%) of HCM cases with ∼20 relevant variants described so far related to this condition. However, TPM1–hypertrophic cardiomyopathy is thought to be associated with high rates of heart failure and sudden death (SD). Purpose To describe the phenotype and genotype of a cohort of adult and pediatric patients with HCM and variants in TPM1 followed up in an inherited cardiovascular disease program of a national reference center. Methods Patients with HCM and TPM1 variants potentially related to the phenotype were retrospectively identified. Genetic test was performed by next generation sequencing panels or clinical exome. Clinical data, any need of intervention (obstruction relief, device implantation, heart transplant) and major adverse cardiovascular events were collected from medical records. We performed co-segregation studies whenever possible. Predictive models in order to support the possible pathogenicity of the variants were also applied. Results We identified 13 individuals (54% females) from 11 families with HCM and variants in TPM1. 12 patients had phenotype and one was a carrier. 5 out of 12 patients (42%) were diagnosed before the age of 12 years, all with severe phenotype. The most frequent pattern was asymmetric septal hypertrophy, with a mean thickness of the septum of 22 mm (range 14–37). 4 cases were obstructive, of which 3 required surgical myectomy. 4 patients required an implanted cardiac defibrillator (ICD), all in childhood. One was in secondary prevention after an aborted SD in a 12-year-old girl. 3 appropriate therapies were recorded in 2 patients during follow-up. A girl underwent heart transplantation at the age of 12 because of angina at rest. At last evaluation 67% were symptomatic, with 3 patients in functional class II and 5 patients in functional class III-IV/IV. 8 missense variants in TPM1 were identified in the 11 families (table 1). All variants are described in Clinvar as variants of unknown significance (VUS). They appear at a very low frequency ( Conclusion This study provides cosegregation data and “in silico” analysis of the potential functional impact of several TPM1 variants, supporting their pathogenicity. In our cohort, HCM related to TMP1 variants is associated with high penetrance (92%), early onset and poor clinical course in childhood and youth. Funding Acknowledgement Type of funding sources: None. Figure 1

Transcatheter Aortic Valve Replacement (TAVR) is considered the treatment in patients older or at high or intermediate risk. Results form contemporary randomized trials in low-risk patients will likely broaden the indication of TAVR, but the data regarding long-term are limited by older population. The aim of this study was to evaluate the survival and the factors predicting mortality after TAVR in according to age. Methods From April 2008 to December 2019, the self-expandable and balloon-expandable prostheses were was implanted in 765 patients with symptomatic severe aortic stenosis with deemed high risk on base to age, Results The mean age in patients 0.001, respectively In-hospital mortality was 4% vs. 3.4%, p=0.404, and the rate of acute complications was 19.6 vs. 16.5%, p=0.168. The late mortality (beyond 30 days) was 36.9 vs. 35.2%, p=0.352. When compared in both groups, there were no differences for the presence of threatening bleeding 3.4% vs. 3.2% (HR = 1.028 [IC95% 0.722–1.463], p=0.516), myocardial infarction 4% vs. 2.5% (HR = 1.263 [IC95% 0.814–1.960], p=0.167), stroke 8% vs. 9.1% (HR = 1.149 [IC95% 0.686–1.925], p=0.347) and acute kidney innjury 14.1% vs. 19.1% (HR=0.1.14 [IC95% 0.969–2.141], p=0.071) and there was difference in between groups in hospitalizations for heart failure 14.6% vs. 7.9% (HR = 1.398 [IC95% 1.075–1.817], p=0.008 Survival at 1, 3, and 5were similar in both groups (88% vs. 89.5%, 73.3 vs. 78.2%, 58.8 vs. 62.6%, log Rank 0.992, p=0.319), respectively, after a mean follow-up of 42.3±27 months. The main predictors of cumulative mortality in young patients were: Charlson index [HR 1.18 (95% CI 1.06–1.30), p=0.001], Acute Kidney Injury [HR 2.21 (95% CI 1.42–3.47), p=0.001], Left ventricular ejection fraction [HR 1.02 (95% CI 1.009–1.035), p=0,001], and protective factor was a higher Karnosfky index [HR 0.98 (95% CI 0.97–0.99) p=0.006]. And in older patients were: Frailty [HR 1.67 (95% CI 1.13–2.47), p=0.010], COPD [HR 2.09 (95% CI 1.41–2.91), p=0,001], Stroke [HR 3.01 (95% CI 1.54–5.89), p=0.001] Charlson index [HR 1.14 (95% CI 1.02–1.27), p=0.015], Acute Kidney Injury [HR 1.57 (95% CI 1.06–2.32), p=0.001. Conclusions TAVR is associated with low complications rate in young and older patients. Survival during follow-up was similar in both groups, but the predictive factors of mortality differ, with greater impact on the comorbidtiy in the elderly patients Funding Acknowledgement Type of funding sources: None.

Background The influence of dental treatment on oral health-related quality of life (OHRQOL) has rarely been evaluated in patients with intellectual disability (ID) through validated questionnaires. The aim of this study was to estimate the changes on OHRQOL in patients with ID after the implementation of an institutional dental treatment program under general anesthesia using the Franciscan Hospital for Children Oral Health-Related Quality of Life questionnaire (FHCOHRQOL-Q). Material and Methods A prospective longitudinal study was conducted on 85 patients (mean age=24.85 years) classified according to DSM-V whose parents/caregivers completed the FHC-OHRQOL-Q. We analyzed the changes in the questionnaire’s overall score and its dimensions from pre-treatment to 12-months of follow-up, considering effect sizes and minimal important differences estimated by the standard measurement error. The impact of clinical and therapeutic factors was evaluated using univariate and multiple linear regression analysis (p

In this paper, we present modified homotopy perturbation method coupled by Laplace transform to solve non-linear problems. As case study modified homotopy perturbation method coupled by Laplace transform is employed in order to obtain an approximate solution for the non-linear differential equation that describes the steady-state of a heat 1-D flow. The comparison between approximate and exact solutions shows the practical potentiality of the method.

DNA fragmentation of cumulus cells could be used as an indicator of oocyte vitrification success as an indirect indicator of the quality of the oocyte. This study was designed to compare the DNA fragmentation of post-mortem equine cumulus cells before or after vitrification in the absence of permeable cryoprotectant agents. Cumulus-oocyte complexes (COCs; n = 56) were recovered from slaughterhouse ovaries and subjected to in vitro maturation (42 hr/38.2°C/5%CO2 ) before (control group) or after a permeable cryoprotectant-free vitrification method using 1 M sucrose (vitrification group). After in vitro maturation, COCs were denuded, and cumulus cells were washed and stored at -80°C until thawing. Cumulus cell samples were processed with the chromatin dispersion test (Ovoselect, Halotech DNA, Spain). Low, high and total DNA fragmentation percentages of cumulus cells were recorded and compared between the two groups by Student's t test. Results were expressed as mean ± SEM. The vitrified group resulted in significantly higher (p

Sperm vitrification is a rapid freezing method in which carbohydrates are used as cryoprotectants. The aim of this study was to determine the optimal volume, concentration and type of carbohydrates for stallion sperm vitrification using 0.25 ml straws in comparison to conventional freezing. Ejaculates (n = 54) were collected from six stallions. For vitrification, straws were filled with different volumes (30, 70, 100 μl), sperm concentrations (50, 100, 200 × 106 sperm/ml) and extenders containing sucrose (20, 100, 200 mM), trehalose (50, 100, 200 mM) and raffinose (50, 100, 200 mM) and plunged into LN2. Conventional freezing was performed in 0.5 ml straws frozen in LN2 vapors. Sperm motility, plasma and acrosome membrane integrities and DNA fragmentation were compared among treatments. The use of straws filled with 100 μl at 100 × 106 sperm/ml with the extender containing 100 mM trehalose resulted in greater values for sperm quality than the other concentrations, volumes and carbohydrates. With vitrification, there were greater values (mean ± SEM; P

The fundamentals of laparoscopic surgery (FLS) program is a simulation-based training program designed to teach and assess the basic skills necessary for laparoscopic surgery. Preliminary work has demonstrated the feasibility of using Skype™ as a telesimulation modality in reliably scoring the exam for remote centers. Google Glass (GG) (Mountain View, California) is referred to as a wearable computer containing a heads-up display and front-facing camera allowing point-of-view video transmission. The objective of this study was to evaluate the feasibility of GG in scoring the technical skills component of the FLS exam. Twenty-eight participants were asked to complete the peg transfer and intracorporeal knot tasks of FLS using both GG and Skype™ setups. GG employed a third-party HIPAA-compliant video software (Pristine; Austin, TX) for video transmission. Participants were alternated between setups and evaluated by onsite and remote proctors. Times and errors were recorded by both proctors. Interrater reliability of their FLS scores was compared using Intraclass Correlation Coefficients (ICCs). GG experience was evaluated based on participant survey responses using a 5-point Likert scale. Interrater reliability for GG demonstrated a statistically significant correlation between onsite (OP) and remote (RP) proctors with ICCs of 0.985 (95% Confidence Interval [CI], 0.969–0.993) and 0.997 (95% CI 0.993–0.998), respectively, for peg and suture tasks. Skype™ demonstrated ICCs of 1.0 (95% CI 1.0–1.0). Average Likert scale responses found GG to be distracting (2.71), obstructive of the view (2.79), and a limitation to task execution (2.75). Overall, there was no statistical difference in scores between GG and Skype™ setups for either the peg (t = 1.446, p = 0.154) or suture task (t = − 0.710, p = 0.480), only 1 participant found the use of GG superior to Skype™. Our findings suggest that although GG are feasible in remote assessment of FLS with strong interrater reliability (ICC > 0.95), Skype™ was the preferred modality.

[EN] Rucaparib (RCP) is a potent selective inhibitor of both PARP-1 and PARP-2 enzymes that induces synthetic lethality in cancer cells. It is used for the treatment of breast and ovarian tumors harboring deleterious germline or somatic cancer susceptibility genes mutations. Although RCP has an indole chromophore in its structure, it displays a bathochromic shift of the absorption band towards the UVA region of sunlight, thus extending the active fraction of solar light able to produce photosensitivity reactions. In this context, it is highly interesting to study the photo(geno)toxicity disorders associated with this drug, bearing in mind that, for dermatologists it is crucial to understand the toxicity mechanism to improve clinical management. In the present work, RCP has shown to be potentially phototoxic, as observed in the neutral red uptake phototoxicity test. Moreover, this significant phototoxicity is attributed to both proteins and genomic DNA, as revealed in the protein photooxidation and comet assays. The results obtained are highly relevant concerning RCP photosafety and become clinically important in the context of identification of the cutaneous adverse events that can be associated with the targeted therapies. Interestingly, this is the first example of a PARP inhibitor able to induce photosensitized damage to biomolecules., The present work was supported by: the Spanish Government (PID2019-105391GB-C22, PID2020-115010RB-100 and BEAGAL 18/00211) and Generalitat Valenciana (ACIF/2018/153 fellowship for A. M-P). We would also like to thank IIS La Fe Microscopy Unit for technical assistance.