Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

The complete genome sequence of a divergent grapevine virus I isolate naturally infecting grapevine in Greece.

A significant number of new members of the genus Vitivirus have been identified recently, mainly due to the advent of high-throughput sequencing (HTS). Grapevine virus I (GVI), which was identified in New Zealand in 2018, is one of these viruses. RNAseq HTS analysis of a Greek grapevine (cv. Daphnia), revealed the presence of a GVI-like isolate (D2-1/19). Sequence analysis confirmed the classification of D2-1/19 as GVI. However, both sequence and phylogenetic data exhibited high levels of variability between D2-1/19 and the previously characterized GVI isolates. This study provides the full-length sequence of a divergent GVI isolate, adding knowledge to the limited information available about this recently identified virus.

Hyaluronic acid biomaterial for human tissue-engineered skin substitutes: Preclinical comparative in vivo study of wound healing.

BACKGROUND: There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. OBJECTIVE: To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. METHODS: Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane® ) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. RESULTS: HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 ± 0.75 g/h/m2 , 0.42 ± 0.08 AU), Autograft (6.91 ± 1.28 g/h/m2 , 0.40 ± 0.08 AU) and healthy mouse skin (6.40 ± 0.43 g/h/m2 , 0.35 ± 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. CONCLUSIONS: This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).

Similarities and differences in tissue distribution of DLK1 and DLK2 during E16.5 mouse embryogenesis.

DLK1 and DLK2 are transmembrane proteins belonging to the EGF-like repeat-containing family that function as non-canonical NOTCH inhibitory ligands. DLK1 is usually downregulated after embryo development and its distribution in some adult and embryonic tissues has been described. However, the expression and role of DLK2 in embryo and adult tissues remains unclear. To better understand the relevance of both proteins during embryo development, we analyzed the expression pattern of DLK1 and DLK2 in 16.5-day-old mouse embryos (E16.5) and evaluated the possible relationship between these two proteins in embryo tissues and cell types. We found that DLK1 and DLK2 proteins exhibited a broad distribution pattern, which was detected in developing mouse organs from each of the three germ layers: ectoderm (brain, salivary glands), mesoderm (skeletal muscle, vertebral column, kidney, cartilage), and endoderm (thymus, lung, pancreas, intestine, liver). The expression pattern of DLK1 and DLK2 indicates that both proteins could play a synergistic role during cell differentiation. This study provides additional information for understanding temporal and site-specific effects of DLK1 and DLK2 during embryo morphogenesis and cell differentiation.

Correction to: Similarities and differences in tissue distribution of DLK1 and DLK2 during E16.5 mouse embryogenesis.

In the original publication of the article, some symbols in Figure 3 were not correctly aligned with the image.

[Effect of the Omicron variant on cumulative incidence of infection and lethality during the sixth wave of the COVID-19 epidemic in Spain]. / Efecto de la variante Ómicron sobre la incidencia y la letalidad durante la 6.ª onda epidémica COVID-19 en España.

The COVID-19 pandemic has strained healthcare systems globally. The successive epidemic waves have shown different characteristics. The Omicron variant of SARS-CoV-2 modified the epidemic behavior that previous variants had followed. The aim of this analysis was to determine the epidemiological characteristics of COVID-19 during the sixth epidemic wave and its differences according to the predominance of the Delta or Omicron variants. The epidemiological data corresponding to the sixth wave of the epidemic published by official organizations were analyzed, and the cumulative incidence of infection (CI-I) and case fatality rates (CFR) were calculated, both for Spain as a whole and for the different Autonomous Communities, in the population as a whole and by age groups. The results showed that the CI-I was higher with the Ómicron variant (10.89% vs 0.75% with Delta) while the CFR was higher with the Delta variant (4.2‰ vs 1.3‰ with Ómicron), as well as a higher rate of hospitalization and ICU admission with the Delta variant.

Sunitinib in combination with gemcitabine for advanced solid tumours: a phase I dose-finding study.

BACKGROUND: This phase I, dose-finding study determined the maximum tolerated dose (MTD), safety, and pharmacokinetics of sunitinib plus gemcitabine in patients with advanced solid tumours. METHODS: Two schedules with sunitinib (25-50 mg per day) and IV gemcitabine (750-1250 mg m(-2)) in escalating doses were studied. First, patients received sunitinib on a 4-weeks-on-2-weeks-off schedule (Schedule 4/2) plus gemcitabine on days 1, 8, 22, and 29. Second, patients received sunitinib on a 2-weeks-on-1-week-off schedule (Schedule 2/1) plus gemcitabine on days 1 and 8. The primary endpoint was determination of MTD and tolerability. RESULTS: Forty-four patients received the combination (Schedule 4/2, n=8; Schedule 2/1, n=36). With no dose-limiting toxicities (DLTs) at maximum dose levels on Schedule 2/1, MTD was not reached. Grade 4 treatment-related AEs and laboratory abnormalities included cerebrovascular accident, hypertension, and pulmonary embolism (n=1 each), and neutropenia (n=3), thrombocytopenia and increased uric acid (both n=2), and lymphopenia (n=1). There were no clinically significant drug-drug interactions. Antitumor activity occurred across dose levels and tumour types. In poor-risk and/or high-grade renal cell carcinoma patients (n=12), 5 had partial responses and 7 stable disease ≥ 6 weeks. CONCLUSION: Sunitinib plus gemcitabine on Schedule 2/1 with growth factor support was well tolerated and safely administered at maximum doses of each drug, without significant drug-drug interactions.

Mathematical modeling of oral absorption and bioavailability of a fluoroquinolone after its precipitation in the gastrointestinal tract.

The objective was to characterize the in vivo absorption and bioavailability (BA) of a low solubility, high permeability fluoroquinolone (CNV97101) that precipitates in the gastrointestinal (GI) tract by mathematical modeling approach. In situ rat intestinal perfusion studies were performed to characterize the absorption mechanism. The oral fraction absorbed in vivo was lower than the predicted based on the in situ intestinal permeability. Two additional routes of administration, intraduodenal (ID) and intraperitoneal (IP) were investigated to explore if precipitation in stomach and subsequent partial re-dissolution were the causes of the lower in vivo BA. Ex vivo precipitation studies with the stomach content of fasted rats were also carried out. Fitting procedures were performed with NONMEM VII 1.2. The in situ experiments confirmed simultaneous passive and carrier-mediated absorption processes. The ex vivo experiments confirmed precipitation in stomach lowering in vivo the oral fraction absorbed compared with the IP and ID administrations. Due to the almost complete availability of CNV97101 following IP administration, a first hepatic pass could be excluded. The ex vivo assay results and the pharmacokinetic modeling of in vivo data supported the hypothesis of precipitation in the stomach and partial re-dissolution. Nevertheless, other factors such as residence time in the GI may reduce the fraction absorbed even for low oral doses for which re-dissolution was almost complete in vivo.

Case-fatality rate of SARS-CoV-2 infection during the third and fifth epidemic waves in Spain: Impact of vaccination.

INTRODUCTION: During the first and second epidemic waves in Spain, the SARS-CoV-2 case-fatality rates (CFRs) showed significant differences between Autonomous Communities (ACs). Comparing CFRs in the third and fifth epidemic waves can provide information on the impact of the different vaccination coverages in the ACs. OBJECTIVE: To evaluate the impact of vaccination on COVID-19 CFRs in the third and fifth epidemic waves in Spain, according to sex, age, and AC. METHODS: This work is an observational, descriptive study which uses data on COVID-19 infections, deaths, and vaccinees published by the Spanish Ministry of Health and the regional Health Departments of the ACs. The third epidemic wave was defined as the period from 26th December 2020 to 19th April 2021, and the fifth wave, from 19th July to 19th September 2021. The CFRs (deaths per 1000 infected [‰]) were calculated according to sex, age group, and AC. The standardized case-fatality ratio (SCFR) was adjusted for age and sex for each wave. We estimated the correlation between CFRs and their change between the two epidemic waves with the vaccination coverages reached at the beginning of the fifth wave. RESULTS: The CFR in the fifth wave (5.7‰) was lower than in the third wave (16.5‰). In addition, the CFR in both waves was significantly higher in men than in women, and in older people than in younger ones. A decrease in the CFR between both waves was only observed in those older than 49. A strong direct and positive correlation (R2a=0.8399) was found between vaccination coverage by age group and decrease in CFR between both epidemic waves. Significant differences were seen between ACs in the two waves, as regards both CFRs and SCFRs. When comparing ACs, a direct correlation was observed between vaccination coverage and CFRs in the fifth wave, and also - although weak - between vaccination coverage and decrease in CFR between both waves. CONCLUSION: The CFR significantly decreased in Spain between the third and the fifth epidemic waves in population aged 50 or older, probably due to the high vaccination coverage in that age group. Differences were observed between CFRs and SCFRs between ACs that are not explained by the differences in vaccination coverage, suggesting the need for further research and evaluation.

A phase I study of sunitinib in combination with FOLFIRI in patients with untreated metastatic colorectal cancer.

BACKGROUND: This study evaluated the maximum tolerated dose (MTD) of sunitinib, a multitargeted tyrosine kinase inhibitor, combined with FOLFIRI (irinotecan 180 mg/m2 given over 90 min i.v. and l-leucovorin 200 mg/m2 given over 120 min on day 1, followed by 5-FU 400 mg/m2 bolus and then 2400 mg/m2 infused over 46 h) in untreated metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: In this multicentre, phase I, open-label, dose-finding trial, FOLFIRI was administered every 2 weeks. Two sunitinib regimens were explored: Schedule 4/2 (4 weeks on, 2 weeks off; 37.5 and 50 mg/day) and continuous daily dosing (CDD; 37.5 and 25 mg/day). Dose-limiting toxic toxicities (DLTs) were evaluated during weeks 1-6. Efficacy was a secondary objective. RESULTS: Thirty-seven patients were enrolled. The 37.5 mg/day Schedule 4/2 cohort had zero of six DLTs, was expanded by 15 patients and declared the MTD. The MTD was exceeded at all other sunitinib doses and schedules; DLTs included febrile neutropenia (n=1), grade 4 neutropenia (n=4) and grade 3 deep vein thrombosis with grade 4 neutropenia (n=1). At the MTD, non-haematologic grade 3/4 adverse events with a frequency of >10% were diarrhoea, vomiting and lethargy, and the objective response rate was 57.9% (95% confidence interval 33.5-79.7). CONCLUSIONS: The MTD of sunitinib combined with FOLFIRI in chemotherapy-naive mCRC was 37.5 mg/day on Schedule 4/2. CDD of sunitinib at 37.5 or 25 mg/day plus FOLFIRI was not feasible.

[The natriuretic peptides in the diagnosis of heart failure in primary care setting]. / Los péptidos natriuréticos en el diagnóstico de la insuficiencia cardíaca en atención primaria.

Heart failure (HF) is a clinical syndrome characterized by symptoms and signs caused by structural and/or functional abnormalities of the heart that cause reduced cardiac output and/or elevated intracardiac pressures at rest or during exercise. Its prevalence and incidence are increasing and it is the leading cause of hospitalization in people over 65years of age. The new American and European guidelines for the management of HF emphasize that the measurement of natriuretic peptide (NP) concentrations constitutes a cornerstone of the diagnostic management of HF, and that the history, physical examination, electrocardiogram, and chest X-ray, complete the beginning of the HF diagnostic process. All these actions and diagnostic tests can be performed and requested from the primary care office. The authors of this document, on behalf of the SEMERGEN Hypertension and Cardiovascular Disease Working Group, have reviewed the most recent scientific evidence related to the preventive diagnostic management of NP in patients with HF in primary care setting.

[SEMERGEN positioning on approaching chronic heart failure in primary care]. / Posicionamiento SEMERGEN en el abordaje de la insuficiencia cardíaca crónica en atención primaria.

Heart failure (HF) is a public health problem that generates a large healthcare burden both in hospitals and in Primary Care (PC). The publication of numerous studies about HF in recent years has led to a paradigm shift in the approach to this syndrome, in which the work of PC teams is gaining greater prominence. The recent guidelines published by the European Society of Cardiology have fundamentally introduced changes in the management of patients with HF. The new proposed strategy, with drugs that reduce hospitalizations and slow the progression of the disease, should now be a priority for all professionals involved. This position document analyzes a proposal for an approach based on multidisciplinary teams with the leadership of family doctors, key to providing quality care throughout the entire process of the disease, from its prevention to the end of the life.

[Case-fatality rates of SARS-CoV-2 infection according to Autonomous Communities during the second epidemic wave in Spain]. / Tasas de letalidad por SARS-CoV-2 según Comunidades Autónomas durante la segunda onda epidémica en España.

INTRODUCTION: In Spain, health systems are transferred to the Autonomous Communities (AC), constituting 19 health systems with differentiated management and resources. During the first epidemic wave of COVID-19, differences were observed in reporting systems and in case-fatality rates (FR) between the AC. The objective of this study was to analyze the FR according to AC. during the 2 nd epidemic wave (from July 20 to December 25, 2020), and its relationship with the prevalence of infection. MATERIAL AND METHODS: A descriptive observational study was carried out, extracting the information available on the number of deaths from COVID-19 registered in the Ministry of Health, the Health Councils and the Public Health Departments of the AC, and according to the excess mortality reported by the System Monitoring of Daily Mortality (MoMo). The prevalence of infection was estimated from the differences between the second and fourth rounds of the ENE-COVID study and their 95% confidence intervals. The global FR (deaths per thousand infected) were calculated according to sex, age groups (< 65 and ≥ 65 years) and AC. The age-Standardized Fatality Rates (SFR) of the AC were calculated using the FR of Spain for each age group. These estimates were made with officially declared deaths (FRo) and excess deaths estimated by MoMo (FRMo). The correlations between the prevalences of infection and the FRo and FRMo were estimated, weighting by population. RESULTS: For the whole of Spain, the FRo during the second epidemic wave was 7.6%, oscillating between 3.8% in the Balearic Islands and 16.4% in Asturias, and the TLMo was 10.1%, oscillating between 4.8% from Madrid and 21.7% in Asturias. Significant differences were observed between the FRo and the FRMo in the Canary Islands, Castilla la Mancha, Extremadura, the Valencian Community, Andalusia and the Autonomous Cities of Ceuta and Melilla. The FRo was significantly higher in men (8.2%) than in women (7.1%). The FRo and FRMo were significantly higher in the age group ≥ 65 years (55.4% and 72.2% respectively) than in the group <65 years (0.5% and 1.4% respectively). The Basque Country, Aragon, Andalusia and Castilla la Mancha presented SFR significantly higher than the global FR of Spain. The correlations between the prevalence of infection and the FRo were inverse. CONCLUSIONS: The case-fatality from COVID-19 during the second epidemic wave in Spain improved compared to the first wave. The case-fatality rates were higher in men and the elderly people, and varied significantly between AC. It is necessary to delve into the analysis of the causes of these differences.

Evaluation of prophylaxis in primary prevention with acetylsalicylic acid in people with diabetes: A scoping review.

BACKGROUND: The efficacy and safety of acetylsalicylic acid (ASA) prophylaxis for the primary prevention of atherosclerotic cardiovascular disease (ACVD) remain controversial in people with diabetes (DM) without ACVD, because the possible increased risk of major bleeding could outweigh the potential reduction in the risk of mortality and of major adverse cardiovascular events (MACE) considered individually or together. OBJECTIVE: To evaluate the overall risk-benefit of ASA prophylaxis in primary prevention in people with DM and to compare the recommendations of the guidelines with the results of the meta-analyses (MA) and systematic reviews (SR). MATERIAL AND METHODS: We searched Medline, Google Scholar, Embase, and the Cochrane Library for SR and MA published from 2009 to 2020 which compared the effects of ASA prophylaxis versus placebo or control followed up for at least one year in people with DM without ACVD. Heterogeneity among the randomized clinical trials (RCT) included in the SR and MA was assessed. Cardiovascular outcomes of efficacy (all-cause mortality [ACM], cardiovascular mortality [CVM], myocardial infarction [MI], stroke and MACE) and of safety (major bleeding events [MBE], major gastrointestinal bleeding events [MGIBE], and intracranial and extracranial bleeding) were shown. RESULTS: The recommendations of 12 guidelines were evaluated. The results of 25 SR and MA that included a total of 20 RCT were assessed. None of the MA or SR showed that ASA prophylaxis decreased the risk of ACM, CVM or MI. Only two of the 19 SR and MA that evaluated ischemic stroke showed a decrease in the stroke risk (mean 20.0% [SD±5.7]), bordering on statistical significance. Almost half of the MA and SR showed, bordering on statistical significance, a risk reduction for the MACE composite endpoint (mean 10.5% [SD±3.3]). The significant increases in MGIBE risk ranged from 35% to 55%. The significant increases in the risk of MBE and extracraneal bleeding were 33.4% (SD±14.9) and 54.5% (SD±0.7) respectively. CONCLUSION: The overall risk-benefit assessment of ASA prophylaxis in primary prevention suggests that it should not be applied in people with DM.

Heat rectification with a minimal model of two harmonic oscillators.

We study heat rectification in a minimalistic model composed of two unequal atoms subjected to linear forces and in contact with effective Langevin baths induced by Doppler lasers. Analytic expressions of the heat currents in the steady state are spelled out. Asymmetric heat transport is found in this linear system if both the bath temperatures and the temperature-dependent bath-system couplings are exchanged. The model can be realized with two ions in either common or individual traps. This physical setting allows for a natural temperature dependence of the coupling to the baths. We also explore the parameter space of the model to optimize asymmetric heat current and find conditions for maximal rectification. High rectification corresponds to a good match of the power spectra of the ions for forward temperature bias and mismatch for reverse bias, which may be understood by the behavior of dissipative normal modes.

[Application of the PCR number of cycle threshold value (Ct) in COVID-19]. / Aplicación del valor umbral del número de ciclos (Ct) de PCR en la COVID-19.

The SARS-CoV-2 pandemic persists with all its virulence despite 650,382,819 doses of COVID vaccine worldwide. The reference test for infection identification is reverse transcription polymerase chain reaction (RT-qPCR). The usefulness of this test may be diminished by simplifying its result as positive or negative. Determining the number of cycles (Ct) in positive RT-qPCR tests can assist in decision-making when interpreted in the clinical context of patients.

A phase I, dose-finding study of sunitinib in combination with irinotecan in patients with advanced solid tumours.

BACKGROUND: Sunitinib is a multitargeted, oral tyrosine kinase inhibitor with antitumour and antiangiogenic activity. We investigated the safety and pharmacokinetics of sunitinib in combination with irinotecan in patients with advanced, refractory solid tumours. METHODS: Sunitinib was initially administered once daily at 37.5 mg per day on days 1-14 of a 21-day cycle, in which irinotecan 250 mg m(-2) was given on day 1. In a second cohort, the sunitinib dose was reduced to 25 mg per day. Blood samples were collected for pharmacokinetic studies. RESULTS: In the sunitinib 37.5 mg per day cohort, 3 out of 10 evaluable patients had objective responses, but dose-limiting toxicities (DLTs) of neutropenia, pneumococcal sepsis, and fatigue were observed. There were no DLTs in the sunitinib 25 mg per day cohort. Paired observations of pharmacokinetic parameter values of sunitinib and irinotecan alone vs the combination did not reveal significant drug-drug interactions. The maximum tolerated dose was defined as sunitinib 25 mg per day (days 1-14) with irinotecan 250 mg m(-2) (day 1), but no activity was observed at this dose. CONCLUSION: Although a higher sunitinib dose of 37.5 mg per day (days 1-14) with irinotecan showed preliminary evidence of antitumour activity, this dose was poorly tolerated. Therefore, this particular combination will not be pursued for further studies.

Spatial configurations and temperature profiles in nonequilibrium steady state of two-species trapped ion systems.

We study Coulomb crystals containing two ion species simultaneously confined in radio frequency traps and coupled to different thermal reservoirs located in two separate regions. We use a three-dimensional model to simulate the trapped bicrystal and show in a numerically rigorous manner the effects of the mass dependence of the trapping frequencies on the underlying nonequilibrium dynamics and the temperature profiles. By solving the classical Langevin equations of motion, we obtain the spatial probability densities of the two ion species and the kinetic temperature profiles across the axial direction of the trap in the nonequilibrium steady state. We analyze trapping conditions leading to bicrystals that exhibit ion conformations ranging from a linear chain of alternating ion species to two- and three-dimensional configurations. The results evidence the spatial segregation of the two ion species due to the mass dependence of the trapping frequencies and the increase of ion delocalization for heavier ion species and/or weaker trapping confinements. We also show the correlation between the increase of the temperature gradient in the bulk and this enhancement of ion delocalization through the trap.

[Analysis of fatality rates case of SARS-CoV-2 infection in the Autonomous Communities of Spain]. / Análisis de las tasas de letalidad de la infección por SARS-CoV-2 en las comunidades autónomas de España.

INTRODUCTION: The SARS-CoV-2 pandemic has posed a real challenge to health systems. In Spain, the heterogeneous distribution of the virus infection and the different health strategies have conditioned the morbidity and fatality rate. The aim of this study was to analyse the lethality of the infection by sex and age range in the Autonomous Communities (AC) of Spain. MATERIAL AND METHODS: To perform the analysis, data were extracted from the Ministry of Health, Regional and Public Health Departments of the different AC. The infected population was estimated from the results of the ENE-COVID19 and the population registered on 1 January 2020 (INE) for the validity of the IgG antibody test with 80% sensitivity and 100% specificity. The case fatality rate (TL) (deaths/1000 estimated infected) by sex and age (<20years, 20-64 and ≥65years) was calculated for each AC. The standardized case fatality ratio (REL) was calculated by the exact method (EPIDAT). RESULTS: The estimated prevalence of SARS-CoV-2 infection in Spain was 6% (range, 1.4% [Ceuta] -14.1% [Community of Madrid]). The TL in Spain was 9,6/1000, ranged per AC from 1/1000 in Melilla to 26.6/1000 in La Rioja, with no correlation between case fatality and prevalence of infection. The TL was higher in men (10.2/1000, ratio 1.17 with respect to women), except in Cataluña (ratio 0.92), and especially high in those over 64years of age in La Rioja (143.5/1000), Asturias (69.2/1000) and Basque Country (46.6/1000). Overall excess REL was found to be over 30% in La Rioja (2.91; 95%CI: 2.36-3.57), Asturias (1.51; 95%CI: 1.27-1.80), Basque Country (1.42; 95%CI: 1.31-1.54) and Extremadura (1.37; 95%CI: 1.20-1.57) and in those over 64 years in Madrid and the Canary Islands. CONCLUSIONS: SARs-CoV-2 virus infection has been very unevenly distributed in the different ACs, with notably differences in TL between ACs, particularly high in La Rioja, Asturias and the Basque Country. Is important to study the excess in TL the population over 64years of age in the ACs of Madrid and the Canary Islands.

Cardiorespiratory effects of epidurally administered ketamine or lidocaine in dogs undergoing ovariohysterectomy surgery: a comparative study.

BACKGROUND: Analgesic and hemodynamic effects of ketamine in subanesthetic doses during surgical anesthesia and postoperative, are due to the action on the N-methyl-D-aspartate receptors (NMDAR). AIMS: To evaluate the intraoperative cardiorespiratory effects provided by ketamine compared to lidocaine, both administered epidurally, in bitches submitted to ovariohysterectomy. METHODS: Thirty-six dogs of different breeds were used in a randomized, prospective, and blinded clinical trial. Two groups were formed: GKET (ketamine 3 mg/kg, n=18) and GLIDO (lidocaine 4 mg/kg, n=18). Animals were premedicated with acepromazine 0.05 mg/kg intravenous. Anesthesia was induced with propofol 5 mg/kg intravenous. Anesthetic maintenance was performed with isoflurane in 100% oxygen. Every 5 min during surgery, heart rate (HR), respiratory rate (RR), esophageal temperature (°C), oxygen saturation (SPO2), end tidal carbon dioxide (ETCO2) and mean arterial pressure (MAP) were monitored. RESULTS: Cardiorespiratory variables during anesthesia were within normal ranges. Heart rate was significantly higher at 5 (108 ± 12 vs 95 ± 11) and 10 (110 ± 11 vs 97 ± 11) min in GKET compared to GLIDO after the start of surgery (P=0.03 and P=0.01, respectively). Mean arterial pressure was higher in GKET, (100 ± 23, 105 ± 35, and 103 ± 35 mmHg) in comparison with GLIDO (66 ± 7, 74 ± 10, and 67 ± 9 mmHg) at 20, 25 and 30 min (P=0.01, P=0.004, and P=0.002, respectively). Mild hypothermia at 25 (36.5 1.3C) and 30 (36.5 1.4C) min in the GKET was recorded. CONCLUSION: Epidural administration of ketamine provides better hemodynamic stability, compared to the use of epidural lidocaine.