Consumption of sucrose in maternal and postnatal stages leads to kidney affectation in adult male rats.

High sugar-sweetened beverage intake has been related to human kidney disease and metabolic alterations. We determine the impact of high sucrose intake from pregnancy until early postnatal days and post-weaning on kidneys from adult male offspring rats. Wistar female rats were mated and assigned into two groups: one control drinking tap water (CM) and another drinking 5 % sucrose diluted in water (SM). Two offspring per mother were randomly allocated into two experimental groups at weaning. One had free access to simple water (CO) and the other to 5 % sucrose (SO) for 14 weeks. After treatment, levels of relative aquaporin-2 (AQP2), glomerulosclerosis index (GI), collecting tube area, perirenal fat, blood creatinine, and blood ureic nitrogen concentration (BUN) were determined. Two-way ANOVA followed by Bonferroni post-hoc test was used, considering P ≤ 0.05 as a significant statistical difference. Sucrose consumption during gestation/lactation and interaction increased AQP2 expression in the renal cortex and BUN concentration. In contrast, gestation/lactation consumption increased collecting tube area, post-weaning consumption favored perirenal fat, and finally, gestation/lactation, post-weaning, and the interaction caused glomerulosclerosis. Our results suggest that the consumption of sucrose water during gestation/lactation or post-weaning or combination triggers pathological changes in the kidneys of adult rats.

Two episodes of bacteremia of zoonotic origin caused by different Streptococcus canis isolates in the same patient within a time span of 1 year.

Two episodes of bacteremia of cutaneous origin in a female patient were caused by two unrelated Streptococcus canis isolates within 1-year interval between the two infection episodes. The most likelihood transmission route in both episodes was a dog pet that habitually licked patient´s legs. Isolates were characterised by antimicrobial susceptibility test and whole genome sequencing. They belonged to sequence type (ST) 40 and 43, respectively. The ST40 isolate harboured antimicrobial resistance genes aadE, ermB and tetO, displaying resistance to erythromycin, clindamycin and tetracyclines, while ST43 isolate did not presented any known antimicrobial resistance determinant and was susceptible to all antibiotics tested. S. canis infections are rare in human; however, attention is needed for patients at risk with companion animals.

Cardiac surgery simulation: Advances in transvenous lead extraction.

The clinical importance of procedures for transvenous lead extraction has increased greatly because the volume of cardiac implantable electronic devices has increased. Consequently, the number of device-related complications requiring lead extraction has also been increasing. Great improvements in lead extraction techniques have occurred in recent years with the development of transvenous lead extraction tools and techniques. Experienced centres can achieve high success rates with infrequent complications. However, even in experienced hands, life-threatening complications can occur, and any physician performing these procedures must be prepared and trained for such eventualities. Moreover, because the occurrence of these stressful situations cannot be accurately predicted, training obtained in simulated environments can be decisive. We have developed a training module that simulates all the ordered steps of a transvenous lead extraction procedure and thus is able to help surgeons refine their surgical techniques and improve their performance.

Maternal and Offspring Sugar Consumption Increases Perigonadal Adipose Tissue Hypertrophy and Negatively Affects the Testis Histological Organization in Adult Rats.

Sugar intake has been associated with the development of male reproductive pathologies because of the increase and dysfunction in different adipose tissue depots. The establishment of these dysfunctions in the early stages of development is unknown. We evaluated the effect of maternal (pregnancy and lactation) and male offspring (from weaning to adulthood) consumption of 5% sucrose on perigonadal adipose tissue (PAT) and testis in adulthood. Moreover, two rat groups were compared, both including pregnant and lactating females: Control (C-drinking tap water) and sugar (S-consuming 5% sucrose solution). From weaning to adulthood with male offspring, four subgroups were formed: Control Mother → Control and Sugar offspring (CC, CS) and Sugar Mother → Control and Sugar offspring (SC, SS). At 120 postnatal days, the testes and PAT were collected and morphologically described. Furthermore, we quantified the number and cross-sectional area of perigonadal adipocytes and their distribution. We found that the males from SC and SS groups showed high PAT weight (p < 0.005), a high number (p < 0.05), and a relative frequency of large adipocytes (p < 0.05), establishing these results during gestational and lactation stages, and enhancing in adulthood since postnatal diet and its interaction. More macrophages, mast cells, and Leydig cells were observed in the interstitial space of the testis for the CS, SC, and SS groups, concluding that consumption of a high-carbohydrate maternal diet, program hypertrophy processes in adult PAT, developing and enhancing with sugar consumption during postnatal life. Furthermore, they are associated with inflammatory processes within the interstitial space of the testis.

Predicting COVID-19 outbreak using open mobility data for minimal disruption on the country's economy

COVID-19 is an infectious disease caused by the SARS-COV-2 coronavirus, which was discovered in late 2019. Within a few months, COVID-19 was declared a global pandemic by the WHO. Several countries adopted social distancing measures, such as self-quarantine, workplace and mobility restrictions, reducing the probability of contact between non-infected and infected people. In general, these measures have a negative impact on low-income economies and small and medium businesses. During the outbreak, several predictive models have been proposed in order to assess the level of saturation that health services might have. Nevertheless, none of them considers information on the peoples mobility to assess the effectiveness of the social distancing policies. In this study, the authors propose a prediction method based on peoples open mobility data from Apple(C) and Google(C) databases to project potential scenarios and monitor case growth. The proposed method shows the importance of monitoring daily case increase for the first 4-6 weeks of the pandemic wave. Active monitoring is crucial to determine the reduction in mobility and proper actions. The results can contribute to health authorities for making timely decisions, preventing the spread of viruses while balancing the reduction of mobility with minimal disruption in peoples economies in future outbreaks.

Effect of the COVID-19 pandemic in stroke code activations in the region of Madrid: A retrospective study.

ABSTRACT: Acute sstroke is the most common time-dependent disease attended in the emergency medical service (EMS) of Madrid (SUMMA 112). Community of Madrid has been one of the most affected regions in Spain by the coronavirus disease 2019 (COVID-19) pandemic. A significant reduction in acute sstroke hospital admissions has been reported during the COVID-19 pandemic compared to the same period 1 year before. As international clinical practice guidelines support those patients with suspected acute stroke should be accessed via EMS, it is important to know whether the pandemic has jeopardized urgent pre-hospital stroke care, the first medical contact for most patients. We aimed to examine the impact of the COVID-19 in stroke codes (SC) in our EMS among 3 periods of time: the COVID-19 period, the same period the year before, and the 2019-2020 seasonal influenza period.We compared the SC frequency among the periods with high cumulative infection rate (above the median of the series) of the first wave of COVID-19, seasonal influenza, and also with the same period of the year before.One thousand one hundred thirty SC were attended during the 3 periods. No significant reduction in SC was found during the COVID-19 pandemic. The reduction of hospital admissions might be attributable to patients attending the hospital by their means. The maximum SC workload seen during seasonal influenza has not been reached during the pandemic. We detected a nonsignificant deviation from the SC protocol, with a slight increase in hospitals' transfers to hospitals without stroke units.

The evolutionary landscape of SARS-CoV-2 variant B.1.1.519 and its clinical impact in Mexico City

The SARS-CoV-2 pandemic is one of the most concerning health problems around the globe. We report the emergence of SARS-CoV-2 variant B.1.1.519 in Mexico City. This variant represented up to 90% of sequenced cases in February 2021. It is characterized by three amino acid changes in the spike protein: T478K, P681H, and T732A. We report the effective reproduction number of B.1.1.519 and present evidence of its geographical origin based on phylogenetic analysis. We also studied its evolution via haplotype analysis and identified the most recurrent haplotypes. Finally, we studied the clinical impact of B.1.1.519: patients infected with variant B.1.1.519 showed a highly significant adjusted odds ratio (aOR) increase of 1.85 over non-B.1.1.519 patients for developing a severe/critical outcome (P = 0.000296, 1.33-2.6 95% CI) and a 2.35-fold increase for hospitalization (P = 0.005, 1.32-4.34 95% CI). The continuous monitoring of this and other variants will be required to control the ongoing pandemic as it evolves.

Plant Occurring Flavonoids as Modulators of the Aryl Hydrocarbon Receptor.

The aryl hydrocarbon receptor (AhR) is a transcription factor deeply implicated in health and diseases. Historically identified as a sensor of xenobiotics and mainly toxic substances, AhR has recently become an emerging pharmacological target in cancer, immunology, inflammatory conditions, and aging. Multiple AhR ligands are recognized, with plant occurring flavonoids being the largest group of natural ligands of AhR in the human diet. The biological implications of the modulatory effects of flavonoids on AhR could be highlighted from a toxicological and environmental concern and for the possible pharmacological applicability. Overall, the possible AhR-mediated harmful and/or beneficial effects of flavonoids need to be further investigated, since in many cases they are contradictory. Similar to other AhR modulators, flavonoids commonly exhibit tissue, organ, and species-specific activities on AhR. Such cellular-context dependency could be probably beneficial in their pharmacotherapeutic use. Flavones, flavonols, flavanones, and isoflavones are the main subclasses of flavonoids reported as AhR modulators. Some of the structural features of these groups of flavonoids that could be influencing their AhR effects are herein summarized. However, limited generalizations, as well as few outright structure-activity relationships can be suggested on the AhR agonism and/or antagonism caused by flavonoids.

Stability of the stroke code during the COVID-19 pandemic in the region of Madrid: a retrospective study

Acute Stroke (AS) is the most common time-dependent disease attended in the Emergency Medicine Service (EMS) of Madrid (SUMMA 112). Community of Madrid has been one of the most affected regions in Spain by the coronavirus disease 2019 (COVID19) pandemic. A significant reduction in AS hospital admissions has been reported during the COVID-19 pandemic compared to the same period one year before. As international clinical practice guidelines support those patients with suspected acute stroke should be accessed via EMS, it is important to know whether the pandemic has jeopardized urgent pre-hospital stroke care, the first medical contact for most patients. We aimed to examine the impact of the COVID-19 in stroke codes (SC) in our EMS among three periods of time: the COVID-19 period, the same period the year before, and the 2019-2020 seasonal influenza period. Methods: We compared the SC frequency among the periods with high cumulative infection rate (above the median of the series) of the first wave of COVID-19, seasonal influenza, and also with the same period of the year before. Results: 1,130 SC were attended during the three periods. No significant reduction in SC was found during the COVID-19 pandemic. The reduction of hospital admissions might be attributable to patients attending the hospital by their means. The maximum SC workload seen during seasonal influenza has not been reached during the pandemic. We detected a non-significant deviation from the SC protocol, with a slight increase in hospitals transfers to hospitals without stroke units.

Prioritisation of population groups with the most interactions for COVID-19 vaccination can substantially reduce total fatalities

Background: The unprecedented rapid development of vaccines against the SARS-CoV-2 virus creates in itself a new challenge for governments and health authorities: the effective vaccination of large numbers of people in a short time and, possibly, with shortage of vaccine doses. To whom vaccinate first and in what sequence, if any at all, to avoid the most fatalities remains an open question. Methods: A compartmental model considering age-related groups was developed to evaluate and compare vaccine distribution strategies in terms of the total avoidable fatalities. Population groups are established based on relevant differences in mortality (due to e.g. their age) and risk-related traits (such as their behaviour and number of daily person-to-person interactions). Vaccination distribution strategies were evaluated for different vaccine effectiveness levels, population coverage and vaccination rate using data mainly from Spain. Findings: Our results show that, if children could also be included in the vaccination, a rollout by priority to groups with the highest number of daily person-to-person interactions can achieve large reductions in total fatalities. This is due to the importance of the avoided subsequent infections inflicted on the rest of the population by highly interactive individuals. If children are excluded from the vaccination, the differences between priority strategies become smaller and appear highly depending on rollout rate, coverage and the levels of self-protection and awareness exercised by the population. Interpretation: These results are in possible contradiction with several published plans for COVID-19 vaccination and highlight the importance of conducting an open comprehensive and thorough analysis of this problem leaving behind possible preconceptions.

An effective COVID-19 response in South America: the Uruguayan Conundrum

BackgroundSouth America has become the new epicenter of the COVID-19 pandemic with more than 1.1M reported cases and >50,000 deaths (June 2020). Conversely, Uruguay stands out as an outlier managing this health crisis with remarkable success. MethodsWe developed a molecular diagnostic test to detect SARS-CoV-2. This methodology was transferred to research institutes, public hospitals and academic laboratories all around the country, creating a "COVID-19 diagnostic lab network". Uruguay also implemented active epidemiological surveillance following the "Test, Trace and Isolate" (TETRIS) strategy coupled to real-time genomic epidemiology. ResultsThree months after the first cases were detected, the number of positive individuals reached 826 (23 deaths, 112 active cases and 691 recovered). The Uruguayan strategy was based in a close synergy established between the national health authorities and the scientific community. In turn, academia rapidly responded to develop national RT-qPCR tests. Consequently, Uruguay was able to perform [~]1,000 molecular tests per day in a matter of weeks. The "COVID-19 diagnostic lab network" performed more than 54% of the molecular tests in the country. This, together with real- time genomics, were instrumental to implement the TETRIS strategy, helping to contain domestic transmission of the main outbreaks registered so far. ConclusionsUruguay has successfully navigated the first trimester of the COVID-19 health crisis in South America. A rapid response by the scientific community to increase testing capacity, together with national health authorities seeking out the support from the academia were fundamental to successfully contain, until now, the COVID-19 outbreak in the country.

A mechanistic population balance model to evaluate the impact of interventions on infectious disease outbreaks: Case for COVID19

Infectious diseases can be devastating, especially when new and highly contagious, producing epidemic outbreaks that can become pandemics. Such is the case of COVID-19, the worst pandemic the world has seen in more than 100 years. Predicting the course and outcomes of such a pandemic in relation to possible interventions is crucial for societal and healthcare planning and forecasting of resource needs. In this work a deterministic model was developed, using elements from the SIR-type models, that describes individuals in a population in compartments by infection stage and age group. The model assumes a close well-mixed community with no migrations. Infection rates and clinical and epidemiological information govern the transitions between stages of the disease. The present model provides a platform to build upon and its current low complexity retains accessibility to both experts and non-experts as well as policy makers to comprehend the variables and phenomena at play. The impact of several possible interventions that have been or may be applied to slow the spread of the COVID-19 outbreak is evaluated. Key findings in our model simulation results indicate that (i) universal social isolation measures may be effective in reducing total fatalities only if they are strict and the average number of daily social interactions is reduced to very low numbers; (ii) selective isolation of only the age groups most vulnerable to the disease (i.e. older than 60) appears almost as effective in reducing total fatalities but at a much lower economic damage; (iii) the use of protective equipment (PPE) appears capable of very significantly reducing total fatalities if implemented extensively and to a high degree; (iv) extensive random testing of the population leading to infection recognition and subsequent immediate (self) isolation of the infected individuals, appears to be an ineffective intervention due to the required (unreachable with existing test sensitivities) high percentage of infection detections and the incapability to be sustained over time; (v) an increase in the number of critical care beds to directly save significant numbers of lives with a direct reduction in total final fatalities per each extra available critical care bed unit.

Fibrosis mediastínica post-irradiación: un factor a tener en cuenta en cirugía cardiaca / Post-radiation mediastinal fibrosis: a factor to take into account in cardiac surgery

Resumen La radioterapia mediastínica es uno de los tratamientos fundamentales de las enfermedades malignas torácicas, pero también representa una causa potencial de complicaciones, tanto a corto como a largo plazo. Se presenta una serie de casos de rotura de vena innominada durante esternotomía media en pacientes con fibrosis mediastínica. Los tres casos descritos corresponden a pacientes intervenidos de cirugía cardiaca con antecedentes de radioterapia mediastínica, entre 15-30 años antes de la cirugía, por tres diferentes enfermedades malignas (linfoma de Hodgkin, timoma y cáncer de mama). En los tres casos se reporta rotura de la vena innominada, con desinserción de su origen en la vena cava superior debido a fibrosis mediastínica intensa.

Abstract Although mediastinal radiotherapy is one of the basic treatments of malignant thoracic diseases, it is also a potential cause of short and long-term complications. A series of cases of rupture of the innominate vein during sternotomy are presented in patients with mediastinal fibrosis. The three cases described correspond to patients intervened by cardiac surgery, with a history of mediastinal radiotherapy between 15 to 30 years before the surgery, due to three different malignant diseases (Hodgkin lymphoma, thymoma, and breast cancer). In the three cases, a rupture of the innominate vein is reported; with de-insertion of its origin in the superior vena cava sue to intense mediastinal fibrosis.

Ligature of the Left Main Coronary Artery after Surgery in Kawasaki Disease: Case Report.

We report a case of a 23-year-old man who was diagnosed with Kawasaki disease that progressed to a coronary aneurysm in the left main coronary artery (LMA). He had suffered from acute coronary syndrome and then underwent an emergent percutaneous coronary angioplasty, in which a polyurethane-covered stent was placed inside the aneurysm. The stent was thrombosed one year later, despite the patient had been treated with anticoagulant and antiplatelet therapy. Emergency percutaneous intervention was then performed. LMA was reopened and stent malposition was observed. Therefore, urgent coronary bypass grafting was performed in which a high degree of competitive flow was observed through the reopened stent. LMA was ligated at the inflow of the aneurysm, resulting in an improvement of graft flow. Left main ligature has not been previously reported.

Ligature of the left main coronary artery after surgery in kawasaki disease: case report

Abstract We report a case of a 23-year-old man who was diagnosed with Kawasaki disease that progressed to a coronary aneurysm in the left main coronary artery (LMA). He had suffered from acute coronary syndrome and then underwent an emergent percutaneous coronary angioplasty, in which a polyurethane-covered stent was placed inside the aneurysm. The stent was thrombosed one year later, despite the patient had been treated with anticoagulant and antiplatelet therapy. Emergency percutaneous intervention was then performed. LMA was reopened and stent malposition was observed. Therefore, urgent coronary bypass grafting was performed in which a high degree of competitive flow was observed through the reopened stent. LMA was ligated at the inflow of the aneurysm, resulting in an improvement of graft flow. Left main ligature has not been previously reported.

The tetrameric peptide LfcinB (20-25)4 derived from bovine lactoferricin induces apoptosis in the MCF-7 breast cancer cell line.

The cytotoxic effect of the tetrameric peptide LfcinB (20-25)4 against breast cancer cell line ATCC® HTB-22™ (MCF-7) was evaluated. The tetrameric peptide exhibited a concentration-dependent cytotoxic effect against MCF-7 cancer cells. The peptide at 22 µM had the maximum cytotoxic effect against MCF-7 cancer cells, reducing their cell viability to ∼20%. The cytotoxic effect of the tetrameric peptide against MCF-7 cells was sustained for 24 hours. Furthermore, the tetrameric peptide did not exhibit a significant cytotoxic effect against the non-tumorogenic trophoblastic cell line, which confirms their selectivity for breast cancer cell lines. The MCF-7 cells treated at 12.2 µM for 1 h exhibited morphological changes characteristic of apoptosis, such as rounded forms and cellular shrinkage. Furthermore, this peptide induces severe cellular damage to MCF-7 cells, mitochondrial membrane depolarization, and increase of cytoplasmic calcium concentration. Our results suggest that it has a significant selective cytotoxic effect against MCF-7 cells, which may be mainly associated with the apoptotic pathway. This peptide, which contains the RRWQWR motif, could be considered to be a promising candidate for developing therapeutic agents for the treatment of breast cancer.

Heparin but not tissue plasminogen activator improves outcomes in donation after circulatory death liver transplantation in a porcine model.

Ischemic-type biliary lesions (ITBLs) arise most frequently after donation after circulatory death (DCD) liver transplantation and result in high morbidity and graft loss. Many DCD grafts are discarded out of fear for this complication. In theory, microvascular thrombi deposited during donor warm ischemia might be implicated in ITBL pathogenesis. Herein, we aim to evaluate the effects of the administration of either heparin or the fibrinolytic drug tissue plasminogen activator (TPA) as means to improve DCD liver graft quality and potentially avoid ITBL. Donor pigs were subjected to 1 hour of cardiac arrest (CA) and divided among 3 groups: no pre-arrest heparinization nor TPA during postmortem regional perfusion; no pre-arrest heparinization but TPA given during regional perfusion; and pre-arrest heparinization but no TPA during regional perfusion. In liver tissue sampled 1 hour after CA, fibrin deposition was not detected, even when heparin was not given prior to arrest. Although it was not useful to prevent microvascular clot formation, pre-arrest heparin did offer cytoprotective effects during CA and beyond, reflected in improved flows during regional perfusion and better biochemical, functional, and histological parameters during posttransplantation follow-up. In conclusion, this study demonstrates the lack of impact of TPA use in porcine DCD liver transplantation and adds to the controversy over whether the use of TPA in human DCD liver transplantation really offers any protective effect. On the other hand, when it is administered prior to CA, heparin does offer anti-inflammatory and other cytoprotective effects that help improve DCD liver graft quality. Liver Transplantation 24 665-676 2018 AASLD.

High Estradiol Differentially Affects the Expression of the Glucose Transporter Type 4 in Pelvic Floor Muscles of Rats / 대한배뇨장애요실금학회지

PURPOSE: To characterize the relationship between serum estradiol levels and the expression of glucose transporter type 4 (Glut4) in the pubococcygeus and iliococcygeus muscles in female rats. METHODS: The muscles were excised from virgin rats during the metestrus and proestrus stages of the estrous cycle, and from sham and ovariectomized rats implanted with empty or estradiol benzoate–filled capsules. The expression of estrogen receptors (ERs) was inspected in the muscles at metestrus and proestrus. Relative Glut4 expression, glycogen content, and serum glucose levels were measured. Appropriate statistical tests were done to identify significant differences (P≤0.05). RESULTS: The pubococcygeus and iliococcygeus muscles expressed ERα and ERβ. Glut4 expression and glycogen content in the pubococcygeus muscle were higher at proestrus than at metestrus. No significant changes were observed in the iliococcygeus muscle. In ovariectomized rats, the administration of estradiol benzoate increased Glut4 expression and glycogen content in the pubococcygeus muscle alone. CONCLUSIONS: High serum estradiol levels increased Glut4 expression and glycogen content in the pubococcygeus muscle, but not in the iliococcygeus muscle.

Accounting for structural and exchange mobility in models of status attainment: Social fluidity in five European countries.

This paper proposes a new method to distinguish structural from exchange mobility in status attainment models with interval endogenous variables. In order to measure structural mobility, the paper proposes to trace occupational and educational changes across generations using information provided by children about their fathers. The validity of the method is assessed by comparing the effects of father's socio-economic status and education on son's status and educational attainments, net of occupational upgrading and educational expansion, in five European countries: Britain, Denmark, Germany, Norway, and Spain, using data from the 2005 EU-SILC survey. The results show that the effect of father's on son's ISEI weakens greatly in all countries after considering occupational upgrading, and that much of father's influence over sons occurs by directing them towards occupations with good economic prospects. Useful extensions to the method are discussed in the conclusions.

Development of an in Silico Model of DPPH• Free Radical Scavenging Capacity: Prediction of Antioxidant Activity of Coumarin Type Compounds.

A quantitative structure-activity relationship (QSAR) study of the 2,2-diphenyl-l-picrylhydrazyl (DPPH•) radical scavenging ability of 1373 chemical compounds, using DRAGON molecular descriptors (MD) and the neural network technique, a technique based on the multilayer multilayer perceptron (MLP), was developed. The built model demonstrated a satisfactory performance for the training ( R 2 = 0.713 ) and test set ( Q ext 2 = 0.654 ) , respectively. To gain greater insight on the relevance of the MD contained in the MLP model, sensitivity and principal component analyses were performed. Moreover, structural and mechanistic interpretation was carried out to comprehend the relationship of the variables in the model with the modeled property. The constructed MLP model was employed to predict the radical scavenging ability for a group of coumarin-type compounds. Finally, in order to validate the model's predictions, an in vitro assay for one of the compounds (4-hydroxycoumarin) was performed, showing a satisfactory proximity between the experimental and predicted pIC50 values.