University of Guayaquil

Abstract The SARS-CoV-2 Omicron BA.1 variant emerged in 2021 1 and has multiple mutations in its spike protein 2 . Here we show that the spike protein of Omicron has a higher affinity for ACE2 compared with Delta, and a marked change in its antigenicity increases Omicron’s evasion of therapeutic monoclonal and vaccine-elicited polyclonal neutralizing antibodies after two doses. mRNA vaccination as a third vaccine dose rescues and broadens neutralization. Importantly, the antiviral drugs remdesivir and molnupiravir retain efficacy against Omicron BA.1. Replication was similar for Omicron and Delta virus isolates in human nasal epithelial cultures. However, in lung cells and gut cells, Omicron demonstrated lower replication. Omicron spike protein was less efficiently cleaved compared with Delta. The differences in replication were mapped to the entry efficiency of the virus on the basis of spike-pseudotyped virus assays. The defect in entry of Omicron pseudotyped virus to specific cell types effectively correlated with higher cellular RNA expression of TMPRSS2 , and deletion of TMPRSS2 affected Delta entry to a greater extent than Omicron. Furthermore, drug inhibitors targeting specific entry pathways 3 demonstrated that the Omicron spike inefficiently uses the cellular protease TMPRSS2, which promotes cell entry through plasma membrane fusion, with greater dependency on cell entry through the endocytic pathway. Consistent with suboptimal S1/S2 cleavage and inability to use TMPRSS2, syncytium formation by the Omicron spike was substantially impaired compared with the Delta spike. The less efficient spike cleavage of Omicron at S1/S2 is associated with a shift in cellular tropism away from TMPRSS2-expressing cells, with implications for altered pathogenesis.

Abstract Angiosperms are the cornerstone of most terrestrial ecosystems and human livelihoods 1,2 . A robust understanding of angiosperm evolution is required to explain their rise to ecological dominance. So far, the angiosperm tree of life has been determined primarily by means of analyses of the plastid genome 3,4 . Many studies have drawn on this foundational work, such as classification and first insights into angiosperm diversification since their Mesozoic origins 5–7 . However, the limited and biased sampling of both taxa and genomes undermines confidence in the tree and its implications. Here, we build the tree of life for almost 8,000 (about 60%) angiosperm genera using a standardized set of 353 nuclear genes 8 . This 15-fold increase in genus-level sampling relative to comparable nuclear studies 9 provides a critical test of earlier results and brings notable change to key groups, especially in rosids, while substantiating many previously predicted relationships. Scaling this tree to time using 200 fossils, we discovered that early angiosperm evolution was characterized by high gene tree conflict and explosive diversification, giving rise to more than 80% of extant angiosperm orders. Steady diversification ensued through the remaining Mesozoic Era until rates resurged in the Cenozoic Era, concurrent with decreasing global temperatures and tightly linked with gene tree conflict. Taken together, our extensive sampling combined with advanced phylogenomic methods shows the deep history and full complexity in the evolution of a megadiverse clade.

Abstract The continuous development of world aquaculture demands new strategies and alternatives aimed to achieve sustainability. The use or microorganisms in aquaculture has greatly evolved during the last two decades. From being considered as a potential threat, during the last years, they have been used as probiotics and inclusively as food source for fish and crustacean. The microbial‐based systems represent one of the most viable strategies to achieve a sustainable aquaculture. In short, these systems are based on the promotion of microbial proliferation, either autotrophic or heterotrophic microorganisms; these microbes are expected to use, recycle and transform the excess of nutrients from faeces, dead organisms, unconsumed food and diverse metabolites into biomass, which would be further consumed by the cultured organisms. Successful results on using microbial‐based systems have been documented around the world; however, there are key aspects to consider and yet to experiment before a system could be implemented. Some of those aspects are analysed in this manuscript, while new advances in the use of microbial‐based systems and recommendations are also presented.

BACKGROUND: Dengue fever, a mosquito-borne viral disease, is now the fastest spreading tropical disease globally. Previous studies indicate that climate and human behavior interact to influence dengue virus and vector (Aedes aegypti) population dynamics; however, the relative effects of these variables depends on local ecology and social context. We investigated the roles of climate and socio-ecological factors on Ae. aegypti population dynamics in Machala, a city in southern coastal Ecuador where dengue is hyper-endemic. METHODS/PRINCIPAL FINDINGS: We studied two proximate urban localities where we monitored weekly Ae. aegypti oviposition activity (Nov. 2010-June 2011), conducted seasonal pupal surveys, and surveyed household to identify dengue risk factors. The results of this study provide evidence that Ae. aegypti population dynamics are influenced by social risk factors that vary by season and lagged climate variables that vary by locality. Best-fit models to predict the presence of Ae. aegypti pupae included parameters for household water storage practices, access to piped water, the number of households per property, condition of the house and patio, and knowledge and perceptions of dengue. Rainfall and minimum temperature were significant predictors of oviposition activity, although the effect of rainfall varied by locality due to differences in types of water storage containers. CONCLUSIONS: These results indicate the potential to reduce the burden of dengue in this region by conducting focused vector control interventions that target high-risk households and containers in each season and by developing predictive models using climate and non-climate information. These findings provide the region's public health sector with key information for conducting time and location-specific vector control campaigns, and highlight the importance of local socio-ecological studies to understand dengue dynamics. See Text S1 for an executive summary in Spanish.

Robotic surgery (RS) is an evolution of minimally invasive surgery that combines medical science, robotics, and engineering. The first robots approved by the Food and Drug Administration (FDA) were the Da Vinci Surgical System and the ZEUS Robotic Surgical System, which have been improving over time. Through the decades, the equipment applied to RS had undergone a wide transformation as a response to the development of new techniques and facilities for the assembly and implementation of the own. RS has revolutionized the field of urology, enabling surgeons to perform complex procedures with greater precision and accuracy, and many other surgical specialties such as gynecology, general surgery, otolaryngology, cardiothoracic surgery, and neurosurgery. Several benefits, such as a better approach to the surgical site, a three-dimensional image that improves depth perception, and smaller scars, enhance range of motion, allowing the surgeon to conduct more complicated surgical operations, and reduced postoperative complications have made robotic-assisted surgery an increasingly popular approach. However, some points like the cost of surgical procedures, equipment-instrument, and maintenance are important aspects to consider. Machine learning will likely have a role to play in surgical training shortly through "automated performance metrics," where algorithms observe and "learn" individual surgeons' techniques, assess performance, and anticipate surgical outcomes with the potential to individualize surgical training and aid decision-making in real time.

Presently, there is no cure or effective treatment for spinal cord injury (SCI). Studies in SCI patients have shown that for a treatment to be effective it must primarily improve their quality of life. Numerous studies have shown that stem cells represent an alternative treatment for various disorders and have shown promise in several disease/trauma states. For instance, the use of autologous CD34+ stem cells has been shown to ameliorate symptoms of several disorders such as leukemia, cardiomyopathy, diabetes, and several autoimmune diseases, including multiple sclerosis. For the first time, we report eight case studies of SCI (four acute, four chronic) with approximately 2 years of follow-up that were administered bone marrow stem cells (BMSCs) via multiple routes: directly into the spinal cord, directly into the spinal canal, and intravenous. Magnetic resonance imaging illustrated morphological changes in the spinal cord of some of the patients following BMSCs administration. Comprehensive evaluations demonstrate improvements in ASIA, Barthel (quality of life), Frankel, and Ashworth scoring. Moreover, in order to assess bladder function, we designed a simple numerical clinical scoring system that demonstrates significant changes in bladder function following BMSCs administration. To date, we have administration BMSCs into 52 patients with SCI and have had no tumor formations, no cases of infection or increased pain, and few instances of minor adverse events. These studies demonstrate that BMSCs administration via multiple routes is feasible, safe, and may improve the quality of life for patients living with SCI.

BACKGROUND: In view of the long term discussion on the appropriateness of the dengue classification into dengue fever (DF), dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS), the World Health Organization (WHO) has outlined in its new global dengue guidelines a revised classification into levels of severity: dengue fever with an intermediary group of "dengue fever with warning sings", and severe dengue. The objective of this paper was to compare the two classification systems regarding applicability in clinical practice and surveillance, as well as user-friendliness and acceptance by health staff. METHODS: A mix of quantitative (prospective and retrospective review of medical charts by expert reviewers, formal staff interviews), semi-quantitative (open questions in staff interviews) and qualitative methods (focus group discussions) were used in 18 countries. Quality control of data collected was undertaken by external monitors. RESULTS: The applicability of the DF/DHF/DSS classification was limited, even when strict DHF criteria were not applied (13.7% of dengue cases could not be classified using the DF/DHF/DSS classification by experienced reviewers, compared to only 1.6% with the revised classification). The fact that some severe dengue cases could not be classified in the DF/DHF/DSS system was of particular concern. Both acceptance and perceived user-friendliness of the revised system were high, particularly in relation to triage and case management. The applicability of the revised classification to retrospective data sets (of importance for dengue surveillance) was also favourable. However, the need for training, dissemination and further research on the warning signs was highlighted. CONCLUSIONS: The revised dengue classification has a high potential for facilitating dengue case management and surveillance.

The interaction between nutrition and the immune system is very complex. In particular, at every stage of the immune response, specific micronutrients, including vitamins and minerals play a key role and often synergistic, and the deficiency of only one essential nutrient may impair immunity. An individual's overall nutrition status and pattern of dietary intake (comprised of nutrients and non-nutritive bioactive compounds and food) and any supplementation with nutraceuticals including vitamins and minerals, can influence positively or negatively the function of the immune system. This influence can occur at various levels from the innate immune system and adaptive immune system to the microbiome. Although there are conflicting evidence, the current results point out that dietary supplementation with some nutrients such as vitamin D and zinc may modulate immune function. An update on the complex relationship between nutrition, diet, and the immune system through gut microbiota is the aim of this current review. Indeed, we will provide the overview of the link among immune function, nutrition and gut microbiota, paying particular attention at the effect of the Mediterranean diet on the immune system, and finally we will speculate the possible role of the main one functional supplements on immune function.

Phytochemical screening of ethanolic extracts of Acnistus arborescens (L.) Schltdl. (Solanaceae); Albizia multiflora (Kunth) Barneby & J.W. Grimes (Fabaceae); Capparidastrum petiolare (Kunth) Hutch. (Capparaceae); Colicodendron scabridum (Kunth) Seem. (Capparaceae); Gronovia scandens L. (Loasaceae); Gustavia angustifolia Benth. (Lecythidaceae); Piscidia carthagenensis Jacq. (Fabaceae); Psidium rostratum Mc Vaugh (Myrtaceae); Psidium guayaquilense Landrum & Cornejo (Myrtaceae); Psidium cf. rostratum Mc Vaugh (Myrtaceae); Salicornia fruticosa L. (Amaranthaceae); Simira ecuadorensis (Standl.) Steyerm. (Rubiaceae); Ruellia floribunda Hook. (Acanthaceae) were assayed. Alkaloids, tannins and terpenoids were the secondary metabolites most frequently found, while flavonoids, quinones, anthraquinones, steroids and saponins were present in less proportion. Folin-Ciocalteu method was used to quantify the total phenolic content in the ethanolic extracts using a calibration curve of gallic acid. The range between 941.97 ± 30.69 and 241.54 ± 15.54 GAE/mg dry extract, has been observed for Psidium guayaquilense and Acnistus arborescens, respectively. On the other hand, antibacterial activity of the ethanolic extracts was evaluated using the disk diffusion agar method against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Vibrio parahaemolyticus ATCC 17802. P. rostratum, P. guayaquilense, P. cf. rostratum, R. floribunda and S. ecuadorensis were the most active extracts against the bacterial assays with minimal inhibitory concentration (MIC) values ranging between 20 and 100 ppm. According to literature, it is most likely that this is the first report on phytochemical screening, total phenolic content and antibacterial activity of ethanolic extracts of these species.

OBJECTIVES: Natural orifice translumenal endoscopic surgery (NOTES) is evolving as a promising alternative for abdominal surgery. IMTN Registry was designed to prospectively document early results of natural orifice surgery among a large group of clinical cases. METHODS: Sixteen centers from 9 countries were approved to participate in the study, based on study protocol requirements and local institutional review board approval. Transgastric and transvaginal endoscopic natural orifice surgery was clinically applied in 362 patients. Intraoperative and postoperative parameters were prospectively documented. RESULTS: Mean operative time for transvaginal cholecystectomy was 96 minutes, compared with 111 minute for transgastric cholecystectomy. A general complication rate of 8.84% was recorded (grade I-II representing 5.8%, grade III-IV representing 3.04%). No requirement for any analgesia was found in one fourth of cholecystectomy and appendectomy patients. CONCLUSIONS: Results of clinical applications of NOTES in the IMTN Study showed the feasibility of different methods of this new minimally invasive alternative for laparoscopic and open surgery.

Mosquitoes, just as other insects produced for the sterile insect technique (SIT), are subjected to several unnatural processes including laboratory colonisation and large-scale factory production. After these processes, sterile male mosquitoes must perform the natural task of locating and mating with wild females. Therefore, the colonisation and production processes must preserve characters necessary for these functions. Fortunately, in contrast to natural selection which favours a suite of characteristics that improve overall fitness, colonisation and production practices for SIT strive to maximize only the few qualities that are necessary to effectively control populations. However, there is considerable uncertainty about some of the appropriate characteristics due to the lack of data. Development of biological products for other applications suggest that it is possible to identify and modify competitiveness characteristics in order to produce competitive mass produced sterile mosquitoes. This goal has been pursued--and sometimes achieved--by mosquito colonisation, production, and studies that have linked these characteristics to field performance. Parallels are drawn to studies in other insect SIT programmes and aquaculture which serve as vital technical reference points for mass-production of mosquitoes, most of whose development occurs--and characteristics of which are determined--in an aquatic environment. Poorly understood areas that require further study are numerous: diet, mass handling and genetic and physiological factors that influence mating competitiveness. Compromises in such traits due to demands to increase numbers or reduce costs, should be carefully considered in light of the desired field performance.

Abstract Aquaculture is an economic activity that faces the unavoidable problem of water quality detriment, which is mainly generated by the improper management of production ponds, including inadequate water circulation and aeration, accumulation of undigested food residues, excretion of metabolic by‐products by the cultivated organisms and other. In addition, the increase in suspended organic matter together with the presence and generation of nitrogen compounds can severely affect the physiology of the animal, leading to significant losses in production. Ammonia (NH3), nitrite (NO2) and nitrate (NO3) are toxic in different scales and environmental conditions; therefore, reducing their concentrations in the culture units has paramount relevance. In this regard, bioflocs are an efficient alternative to transform nitrogen compounds into a non‐toxic form, taking advantage of the capabilities of the microbial communities conforming them. Also, nitrogen can be harnessed and incorporated as organic nitrogen, making the biofloc a source of useful natural food for the cultivated organism. The substantial reduction in the rate of water exchange favoured by the biofloc technology (BFT) is a beneficial advantage for both the production systems and the environment, diminishing the risk of introducing pathogens into the pond in parallel with the improvement in the water quality of effluents. Ammonia oxidation is an advantage adding value to the BFT systems and is discussed in this review.

BACKGROUND: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients. METHODS: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality. RESULTS: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality. CONCLUSION: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population.

Glaucoma is prominent in a variety of nations, with the United States and Europe being two of the most famous. Glaucoma now affects around 78 million people throughout the world (2020). By the year 2040, it is expected that there will be 111.8 million cases of glaucoma worldwide. In countries that are still building enough healthcare infrastructure to cope with glaucoma, the ailment is misdiagnosed nine times out of ten. To aid in the early diagnosis of glaucoma, the creation of a detection system is necessary. In this work, the researchers propose using a technology known as deep learning to identify and predict glaucoma before symptoms appear. The glaucoma dataset is used in this deep learning algorithm that has been proposed for analyzing glaucoma images. To get the required results when using deep learning principles for the job of segmenting the optic cup, pretrained transfer learning models are integrated with the U-Net architecture. For feature extraction, the DenseNet-201 deep convolution neural network (DCNN) is used. The DCNN approach is used to determine whether a person has glaucoma. The fundamental goal of this line of research is to recognize glaucoma in retinal fundus images, which will aid in assessing whether a patient has the condition. Because glaucoma can affect the model in both positive and negative ways, the model's outcome might be either positive or negative. Accuracy, precision, recall, specificity, the F-measure, and the F-score are some of the metrics used in the model evaluation process. An extra comparison study is performed as part of the process of establishing whether the suggested model is accurate. The findings are compared to convolution neural network classification methods based on deep learning. When used for training, the suggested model has an accuracy of 98.82 percent and an accuracy of 96.90 percent when used for testing. All assessments show that the new paradigm that has been proposed is more successful than the one that is currently in use.

In recent years, some methods of sentiment analysis have been developed for the health domain; however, the diabetes domain has not been explored yet. In addition, there is a lack of approaches that analyze the positive or negative orientation of each aspect contained in a document (a review, a piece of news, and a tweet, among others). Based on this understanding, we propose an aspect-level sentiment analysis method based on ontologies in the diabetes domain. The sentiment of the aspects is calculated by considering the words around the aspect which are obtained through N -gram methods ( N -gram after, N -gram before, and N -gram around). To evaluate the effectiveness of our method, we obtained a corpus from Twitter, which has been manually labelled at aspect level as positive, negative, or neutral. The experimental results show that the best result was obtained through the N -gram around method with a precision of 81.93%, a recall of 81.13%, and an <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>F</mml:mi></mml:mrow></mml:math>-measure of 81.24%.

OBJECTIVE: The purpose of the present investigation was to assess sexual function among middle-aged women and determine related risk factors (personal and partner) for sexual dysfunction. METHODS: In this cross-sectional study, women aged 40-59 years were requested to fill out the Female Sexual Function Index (FSFI) and a general demographic questionnaire containing personal and partner data. RESULTS: A total of 409 women with a mean age of 47 +/- 5.3 years were surveyed. Of these, 42.1% were premenopausal, 24.4% perimenopausal and 33.5% postmenopausal. At the time of survey, 10.5% of women were hysterectomized, 1.5% used psychotropic drugs, and 9.8% were on hormone therapy (HT) for the menopause; 28.1% had less than 12 years of schooling and 80.4% had only one partner at the moment of survey. Among their male partners, 7.3% abused alcohol, 10.3% had erectile dysfunction, 11.2% premature ejaculation and 63.83% were faithful partners. Mean (+/- standard deviation) scores for the FSFI domains were: desire (3.7 +/- 1.2), arousal (3.1 +/- 2.5), lubrication (3.3 +/- 2.6), orgasm (2.6 +/- 2.3), satisfaction (4 +/- 1.7), and pain/dyspareunia (3.2 +/- 2.6). The mean total FSFI score was 20.1 +/- 12.4 (median 24.7). In this series, the prevalence of female sexual dysfunction (FSFI score <or=26.55) was 55.7%, with women presenting difficulties across all domains of female sexual function but mostly in the dyspareunia and lubrication domains. Logistic regression analysis determined that female age (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.6-6.8), p = 0.001), postmenopausal status (OR 2.8, 95% CI 1.3-6.1, p = 0.007), partner's age (OR 2.0, 95% CI 1-4, p = 0.03), educational level (OR 2.7, 95% CI 1.5-5, p = 0.001), and the presence of erectile dysfunction (OR 3.8, 95% CI 1.3-10.9, p = 0.01) and premature ejaculation (OR 4.1, 95% CI 1.4-11.7, p = 0.0001) significantly increased the risk for female sexual dysfunction. Partner faithfulness (OR 0.2, 95% CI 0.1-0.4, p = 0.001) and menopausal HT use (OR 0.4, 95% CI 0.1-1, p = 0.04) decreased this risk. CONCLUSIONS: In this series, male sexual health and demographic profile and female HT use were relevant determinants for sexual functioning among middle-aged women.

BACKGROUND: Dengue fever, a mosquito-borne viral disease, is a rapidly emerging public health problem in Ecuador and throughout the tropics. However, we have a limited understanding of the disease transmission dynamics in these regions. Previous studies in southern coastal Ecuador have demonstrated the potential to develop a dengue early warning system (EWS) that incorporates climate and non-climate information. The objective of this study was to characterize the spatiotemporal dynamics and climatic and social-ecological risk factors associated with the largest dengue epidemic to date in Machala, Ecuador, to inform the development of a dengue EWS. METHODS: The following data from Machala were included in analyses: neighborhood-level georeferenced dengue cases, national census data, and entomological surveillance data from 2010; and time series of weekly dengue cases (aggregated to the city-level) and meteorological data from 2003 to 2012. We applied LISA and Moran's I to analyze the spatial distribution of the 2010 dengue cases, and developed multivariate logistic regression models through a multi-model selection process to identify census variables and entomological covariates associated with the presence of dengue at the neighborhood level. Using data aggregated at the city-level, we conducted a time-series (wavelet) analysis of weekly climate and dengue incidence (2003-2012) to identify significant time periods (e.g., annual, biannual) when climate co-varied with dengue, and to describe the climate conditions associated with the 2010 outbreak. RESULTS: We found significant hotspots of dengue transmission near the center of Machala. The best-fit model to predict the presence of dengue included older age and female gender of the head of the household, greater access to piped water in the home, poor housing condition, and less distance to the central hospital. Wavelet analyses revealed that dengue transmission co-varied with rainfall and minimum temperature at annual and biannual cycles, and we found that anomalously high rainfall and temperatures were associated with the 2010 outbreak. CONCLUSIONS: Our findings highlight the importance of geospatial information in dengue surveillance and the potential to develop a climate-driven spatiotemporal prediction model to inform disease prevention and control interventions. This study provides an operational methodological framework that can be applied to understand the drivers of local dengue risk.

Novel pharmacologic treatment options reduce mortality and morbidity in a cost-effective manner in patients with heart failure (HF). Undisputedly, the effective implementation of these agents is an essential element of good clinical practice, which is endorsed by the European Society of Cardiology (ESC) guidelines on acute and chronic HF. Yet, physicians struggle to implement these therapies as they have to balance the true and/or perceived risks versus their substantial benefits in clinical practice. Any worsening of biomarkers of renal function is often perceived as being disadvantageous and is in clinical practice one of the most common reasons for ineffective drug implementation. However, even in this context, they clearly reduce mortality and morbidity in HF with reduced ejection fraction (HFrEF) patients, even in patients with poor renal function. Furthermore these agents are also beneficial in HF with mildly reduced ejection fraction (HFmrEF) and sodium-glucose cotransporter 2 (SGLT2) inhibitors more recently demonstrated a beneficial effect in HF with preserved ejection fraction (HFpEF). The emerge of several new classes (angiotensin receptor-neprilysin inhibitor [ARNI], SGLT2 inhibitors, vericiguat, omecamtiv mecarbil) and the recommendation by the 2021 ESC guidelines for the diagnosis and treatment of acute and chronic HF of early initiation and titration of quadruple disease-modifying therapies (ARNI/angiotensin-converting enzyme inhibitor + beta-blocker + mineralocorticoid receptor antagonist and SGLT2 inhibitor) in HFrEF increases the likelihood of treatment-induced changes in renal function. This may be (incorrectly) perceived as deleterious, resulting in inertia of starting and uptitrating these lifesaving therapies. Therefore, the objective of this consensus document is to provide advice of the effect HF drugs on renal function.

BACKGROUND: The unexpected results of the Women's Health Initiative study have decreased the use of conventional hormone therapy (HT), changing physicians' and patients' attitudes towards HT and increasing their interest in alternative options. OBJECTIVE: The present study aimed to evaluate the effect of isoflavones contained in red clover extracts (Trifolium pratense) on menopausal symptoms, lipids and vaginal cytology in menopausal women. METHODS: Sixty postmenopausal women aged >40 years, non-users of HT, with Kupperman index score 15, were double-blindly randomized to receive either a commercially available red clover isoflavone supplement (80 mg/day) or placebo for 90 days. Subsequently, after a 7-day washout period, subjects switched to receive the opposite treatment for a further 90 days. Kupperman index score was determined and fasting blood and vaginal cytologic sampling performed at baseline, 90 and 180 days. RESULTS: Fifty-three women (88.3%) completed the trial. Mean age was 51.3 +/- 3.5 years, 69.7% of the women were aged 50 years or more. There was no significant effect on body mass index, weight or blood pressure after either treatment phase. Baseline Kupperman index score decreased significantly after each treatment phase, with the decrease more pronounced after the isoflavone phase (baseline: 27.2 +/- 7.7; after isoflavone: 5.9 +/- 3.9; after placebo: 20.9 +/- 5.3, p < 0.05). Red clover isoflavone supplementation significantly decreased the rate of menopausal symptoms and had a positive effect on vaginal cytology as expressed by improvement in karyopyknotic, cornification and basal cell maturation indices. Mean total cholesterol, low-density lipoprotein-cholesterol and triglyceride levels also decreased; however, only the latter was significantly lower compared with placebo. CONCLUSIONS: Compared with placebo, red clover isoflavone supplementation in postmenopausal women significantly decreased menopausal symptoms and had a positive effect on vaginal cytology and triglyceride levels.

Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite its international aggressive extension, with a significant morbidity and mortality, the impact of renal function on its prognosis is uncertain. Analysis from the international HOPE-Registry (NCT04334291). The objective was to evaluate the association between kidney failure severity on admission with the mortality of patients with SARS-CoV-2 infection. Patients were categorized in 3 groups according to the estimated glomerular filtration rate on admission (eGFR > 60 mL/min/1.73 m 2 , eGFR 30–60 mL/min/1.73 m 2 and eGFR < 30 mL/min/1.73 m 2 ). 758 patients were included: mean age was 66 ± 18 years, and 58.6% of patient were male. Only 8.5% of patients had a history of chronic kidney disease (CKD); however, 30% of patients had kidney dysfunction upon admission (eGFR < 60 mL/min/1.73 m 2 ). These patients received less frequently pharmacological treatment with hydroxychloroquine or antivirals and had a greater number of complications such as sepsis (11.9% vs 26.4% vs 40.8%, p < 0.001) and respiratory failure (35.4% vs 72.2% vs 62.0%, p < 0.001) as well as a higher in-hospital mortality rate (eGFR > 60 vs eGFR 30-60 vs and eGFR < 30, 18.4% vs 56.5% vs 65.5%, p < 0.001). In multivariate analysis: age, hypertension, renal function, 0 2 saturation < 92% and lactate dehydrogenase elevation on admission independently predicted all-cause mortality. Renal failure on admission in patients with SARS-CoV-2 infection is frequent and is associated with a greater number of complications and in-hospital mortality. Our data comes from a multicenter registry and therefore does not allow to have a precise mortality risk assessment. More studies are needed to confirm these findings.