Quantum detector tomography applied to the human visual system: a feasibility study.

We show that quantum detector tomography can be applied to the human visual system to explore human perception of photon number states. In detector tomography, instead of using very hard-to-produce photon number states, the response of a detector to light pulses with known photon statistics of varying intensity is recorded, and a model is fitted to the experimental outcomes, thereby inferring the detector's photon number state response. Generally, light pulses containing a Poisson-distributed number of photons are utilized, which are very easy to produce in the lab. This technique has not been explored to study the human visual system before because it usually requires a very large number of repetitions not suitable for experiments on humans. Yet, in the present study we show that detector tomography is feasible for human experiments. Assuming a simple model for this accuracy, the results of our simulations show that detector tomography is able to reconstruct the model using Bayesian inference with as few as 5000 trials. We then optimize the experimental parameters in order to maximize the probability of showing that the single-photon accuracy is above chance. As such, our study opens the road to study human perception on the quantum level.

Electrocardiogram-based mortality prediction in patients with COVID-19 using machine learning.

BACKGROUND AND PURPOSE: The electrocardiogram (ECG) is frequently obtained in the work-up of COVID-19 patients. So far, no study has evaluated whether ECG-based machine learning models have added value to predict in-hospital mortality specifically in COVID-19 patients. METHODS: Using data from the CAPACITY-COVID registry, we studied 882 patients admitted with COVID-19 across seven hospitals in the Netherlands. Raw format 12-lead ECGs recorded within 72 h of admission were studied. With data from five hospitals (n = 634), three models were developed: (a) a logistic regression baseline model using age and sex, (b) a least absolute shrinkage and selection operator (LASSO) model using age, sex and human annotated ECG features, and (c) a pre-trained deep neural network (DNN) using age, sex and the raw ECG waveforms. Data from two hospitals (n = 248) was used for external validation. RESULTS: Performances for models a, b and c were comparable with an area under the receiver operating curve of 0.73 (95% confidence interval [CI] 0.65-0.79), 0.76 (95% CI 0.68-0.82) and 0.77 (95% CI 0.70-0.83) respectively. Predictors of mortality in the LASSO model were age, low QRS voltage, ST depression, premature atrial complexes, sex, increased ventricular rate, and right bundle branch block. CONCLUSION: This study shows that the ECG-based prediction models could be helpful for the initial risk stratification of patients diagnosed with COVID-19, and that several ECG abnormalities are associated with in-hospital all-cause mortality of COVID-19 patients. Moreover, this proof-of-principle study shows that the use of pre-trained DNNs for ECG analysis does not underperform compared with time-consuming manual annotation of ECG features.

Heterotopic autotransplantation of equine ovarian tissue using intramuscular versus subvulvar grafting sites: Preliminary results.

Ovarian tissue transplantation (OTT) is a technique well established and successfully applied in humans using mainly orthotopic or heterotopic transplantation sites. In livestock, OTT is still in its infancy and, therefore, different aspects of the technique, including the efficiency of different heterotopic OTT sites as well as the potential effect of age (i.e., young vs. old mares) in the ovarian graft quality, need to be investigated. The present study investigated the efficacy of the intramuscular (IM) or the novel subvulvar mucosa (SV) heterotopic autotransplantation sites to maintain the survivability of the grafts for 3 and 7 days post-OTT. Ovarian biopsy fragments were obtained in vivo and distributed to the following treatments: Fresh control group (ovarian fragments immediately fixed), SV-3, IM-3, SV-7, and IM-7. During and after graft harvesting, the macroscopic characteristics of the grafts (i.e., adherence, morphology, and bleeding) were scored, and the percentages of morphologically normal and developing preantral follicles as well as the follicular and stromal cell densities of the grafts were evaluated. The results were that similar (P > 0.05) macroscopic scores were observed between both transplantation sites 7 days post-OTT, with positive correlations (P < 0.01) found among adherence, morphology, and bleeding of the grafts. A lower (P < 0.05) percentage of morphologically normal follicles was found 7 days post-OTT in the SV site (82%) compared with the Fresh control group (99%) and IM site (95%); however, the percentages of developing follicles were similar (P > 0.05) between both transplantation sites 7 days post-OTT (30-43%). Although similar (P > 0.05) follicular densities were found in both transplantation sites in young and old mares at 3 and 7 days post-OTT, large individual variation in the follicular depletion rate was observed regardless of transplantation site. The Fresh control group and SV-7 treatments had higher (P < 0.05) stromal cell densities in young and old mares compared with both IM-7 treatments. When comparing transplant sites between young and old mares, the follicular density in old mares and the stromal cell density in young mares were greater (P < 0.05) in the SV than in the IM site. In conclusion, even though the transplantation sites differentially affected some end points, overall comparable findings of the OTT technique using both heterotopic autotransplantation sites (i.e., IM and SV) for equine ovarian tissue were observed.

The effects of ACE2 expression mediating pharmacotherapy in COVID-19 patients.

BACKGROUND: There has been debate on the use of angiotensin-converting enzyme­2 (ACE2) expression mediating pharmacotherapy in COVID-19 infected patients. Although it has been suggested that these drugs might lead to a higher susceptibility and severity of COVID-19 infection, experimental data suggest these agents may reduce acute lung injury via blocking angiotensin-II-mediated pulmonary permeability, inflammation and fibrosis. METHODS: A systematic literature search was performed to answer the question: What is the effect of medications that influence ACE2 expression (ACE inhibitors (ACEIs), angiotensin receptor blockers (ARBs), nonsteroidal anti-inflammatory drugs (NSAIDs) and thiazolidinediones) on the outcomes of COVID-19? Relevant outcome measures were mortality (crucial), hospital admission, length of stay, thromboembolic complications (pulmonary embolism, stroke, transient ischaemic attack), need for mechanical ventilation, acute kidney injury and use of renal replacement therapy. Medline and Embase databases were searched with relevant search terms until 24 June 2020. After systematic analysis, nine studies were included. RESULTS: The results were described for two different groups, an overall group in which all users were compared with non-users and a group in which only hypertensive patients were included. Within each group a distinction was made between results for ACEI/ARB use, ACEI use, ARB use, NSAID use and thiazolidinedione use. None of the studies demonstrated increased mortality in the two groups. Furthermore, none of the studies showed an effect on other outcome measures in COVID-19, such as ICU admission, length of hospital stay, thromboembolic complications, need for mechanical ventilation, acute kidney failure or need for renal replacement therapy. However, the level of evidence of all studies varied from 'moderate' to 'very low', according to the GRADE methodology. CONCLUSION: Analysis of the literature demonstrated that there was insufficient evidence to answer our objective on the effect of ACE2 expression mediating pharmacotherapy on outcome in COVID-19 patients, especially due to the low scientific quality of the described studies. Randomised controlled studies are needed to answer this question.

The Netherlands Sports Cardiology Map: a step towards sports cardiology network medicine for patient and athlete care.

Sports cardiology is a rapidly evolving subspecialty of cardiology, with a growing demand for expertise. To improve patient care, clinicians, patients, and athletes (recreational to elite) should be able to easily identify specialised care pathways, expertise centres and clinicians with sports cardiology expertise. To this purpose, several international societies and organisations recommend establishing a local and national sports cardiology infrastructure. We therefore aimed to establish The Netherlands Sports Cardiology Map. We conducted a web-based survey, which was published on the Netherlands Society of Cardiology home page (2019-2020) and in which each cardiology department or clinic was asked to provide information on sports cardiology expertise and the current infrastructure. Of the 46 respondent centres, 28 (61%) reported that they had expertise in sports cardiology, of which 22 (79%) had specific expertise in one or more specific types of sports. Integrated multidisciplinary meetings were reported by 43% of the centres (n = 12/28). Only two centres reported ongoing research projects that had been approved by an institutional review board. The Netherlands Sports Cardiology Map is an important step towards improving the existing infrastructure and developing network medicine for sports cardiology.

Heterozygous loss of Rbm24 in the adult mouse heart increases sarcomere slack length but does not affect function.

RNA-binding proteins are key regulators of post-transcriptional processes such as alternative splicing and mRNA stabilization. Rbm24 acts as a regulator of alternative splicing in heart and skeletal muscle, and is essential for sarcomere assembly. Homozygous inactivation of Rbm24 in mice disrupts cardiac development and results in embryonic lethality around E12.5. In the present study, we generated somatic Rbm24 knockout (KO) mice and investigated the effects of reduced levels of Rbm24 in the adult heart. Due to the embryonic lethality of Rbm24 KO mice, we examined cardiac structure and function in adult Rbm24 heterozygotes (HETs). Rbm24 protein expression was 40% downregulated in HET hearts compared to WT hearts. Force measurements on isolated membrane-permeabilized myocytes showed increased sarcomere slack length and lower myofilament passive stiffness in adult Rbm24 HET compared to wildtype cardiomyocytes. As a result of the differences in sarcomere slack length, the relations between force development and sarcomere length differed between WT and Rbm24 HET hearts. No differences in sarcomere structure and titin isoform composition were observed. Likewise, in vivo cardiac function and myocardial structure was unaltered in Rbm24 HET mice compared to WT, at baseline and upon pressure overload after transverse aortic constriction. In conclusion, we generated a somatic Rbm24 KO model and recapitulated the previously reported embryonic phenotype. In adult Rbm24 HET cardiomyocytes we observed increased sarcomere slack length, but no difference in sarcomere structure and cardiac function.

[Effectiveness of a ketogenic diet in children with refractory epilepsy: a systematic review]. / Efectividad de la dieta cetogenica en niños con epilepsia refractaria: revision sistematica.

INTRODUCTION: Epilepsy is a brain disorder that affects both children and adults. From the 1920s the ketogenic diet has gained prestige as another treatment option for patients with refractory epilepsy. SUBJECTS AND METHODS: A summary of the evidence will be made through a systematic review of randomized clinical trials that have compared a single ketogenic diet with other diet for the management of these patients. AIM: To determine the effectiveness of the ketogenic diet in reducing episodes of seizures in patients with refractory epilepsy. The search strategy included randomized controlled trials and controlled clinical trials. Databases used were Medline, LILACS, Central and CINAHL. RESULTS: Six articles that met our elegibility criteria. CONCLUSIONS: There is limited evidence that the ketogenic diet compared to the medium-chain triglyceride diet is more effective in reducing the frequency of seizures. There is also moderate evidence that classical ketogenic diet compared to the gradual diet (2.5:1 and 3:1) is more effective in reducing seizures. There is moderate evidence that classical ketogenic diet compared to Atkins diet is more effective in reducing the frequency of seizure. The decision to apply this type of diet should also be based on costs, preferences and safety of treatment. It should also take into account the likelihood that studies have indexing problems have been left out of the review.

TITLE: Efectividad de la dieta cetogenica en niños con epilepsia refractaria: revision sistematica.Introduccion. La epilepsia es una patologia cerebral que afecta tanto a niños como a adultos. Desde los años veinte, la dieta cetogenica ha ganado prestigio como otra opcion de tratamiento en pacientes con epilepsia refractaria. Sujetos y metodos. Se realiza una sintesis de la evidencia a traves de una revision sistematica de ensayos clinicos aleatorizados que hayan comparado una dieta cetogenica sola con otros tipos de dieta para el tratamiento de estos pacientes. Objetivo. Determinar la efectividad de la dieta cetogenica en la disminucion de los episodios de convulsiones en pacientes con epilepsia refractaria. La estrategia de busqueda incluyo ensayos clinicos aleatorizados y ensayos clinicos controlados. Las bases de datos usadas fueron: Medline, LILACS, Central y CINAHL. Resultados. Se obtuvieron seis articulos que cumplian con los criterios de elegibilidad. Conclusiones. Existe evidencia limitada de que la dieta cetogenica en comparacion con la dieta de trigliceridos de cadena media es mas efectiva en disminuir la frecuencia de las convulsiones. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta gradual (2,5:1 y 3:1) es mas efectiva para disminuir las crisis epilepticas. Existe evidencia moderada de que la dieta cetogenica clasica en comparacion con la dieta Atkins es mas efectiva para disminuir la frecuencia de convulsiones en tres meses. La decision de aplicar este tipo de dietas tambien debe basarse en costes, preferencias y seguridad del tratamiento. Ademas, debe considerarse la probabilidad de que algunos estudios, por problemas de indizacion, hayan quedado fuera de la revision.

MicroRNAs in heart failure: new targets in disease management.

Heart failure is the leading cause of mortality in Western society and represents the fastest growing subclass of cardiovascular diseases. An increasing body of evidence indicates an important role for microRNAs (miRNAs) in the pathogenesis and progression of heart failure. miRNAs are small noncoding RNAs that regulate expression of target genes by sequence-specific binding to the 3' untranslated region of messenger RNA, which results in degradation or translational repression. To date, many miRNAs (and their targets) that play a role in diverse aspects of cardiac remodeling and heart failure development have been identified. Here, we give an overview of these miRNAs and their role in cardiac pathogenesis. In addition, we provide brief insight into the potential of miRNAs as novel therapeutic targets for heart failure.

Exercise related ventricular arrhythmias are related to cardiac fibrosis in hypertrophic cardiomyopathy mutation carriers.

AIMS: Hypertrophic cardiomyopathy (HCM) is a frequent cause of sudden cardiac death (SCD) due to exercise-related ventricular arrhythmias (ERVA); however the pathological substrate is uncertain. The aim was to determine the prevalence of ERVA and their relation with fibrosis as determined by cardiac magnetic resonance imaging (CMR) in carriers of an HCM causing mutation. METHODS: We studied the prevalence and origin of ERVA and related these with fibrosis on CMR in a population of 31 HCM mutation carriers. RESULTS: ERVA occurred in seven patients (23%) who all showed evidence of fibrosis (100% ERVA(+) vs. 58% ERVA(-), p = 0.04). No ventricular tachycardia or ventricular fibrillation occurred. In patients with ERVA, the extent of fibrosis was significantly larger (8 ± 4% vs. 3 ± 4%, p = 0.02). ERVA originated from areas with a high extent of fibrosis or regions directly adjacent to these areas. CONCLUSIONS: ERVA in HCM mutation carriers arose from the area of fibrosis detected by CMR; ERVA seems closely related to cardiac fibrosis. Fibrosis as detected by CMR should be evaluated as an additional risk factor to further delineate risk of SCD in carriers of an HCM causing mutation.

Hereditary muscular dystrophies and the heart.

Cardiac disease is a common clinical manifestation of neuromuscular disorders, particularly of muscular dystrophies. Heart muscle cells as well as specialized conducting myocardial fibres may be affected by the dystrophic process. The incidence and nature of cardiac involvement vary with different types of muscular dystrophies. Some mainly lead to myocardial disease, resulting in cardiomyopathy and heart failure, while others particularly affect the conduction system, leading to arrhythmias and sudden death. As prognosis of muscular dystrophy patients may be directly related to cardiac status, surveillance and timely management of cardiac complications are important. However, recognition of cardiac involvement requires active investigation and remains challenging since typical signs and symptoms of cardiac dysfunction may not be present and progression is unpredictable. In this review, we present a comprehensive overview of hereditary muscular dystrophies associated with cardiac disease to provide an efficient strategy for the expertise and management of these diseases.

No effect of rosuvastatin on left ventricular hypertrophy in patients with hypertension: a prospective randomised open-label study with blinded endpoint assessment.

BACKGROUND: This study tested the hypothesis that statins may reduce left ventricular hypertrophy (LVH) in patients with hypertension and LVH. METHOD: A prospective randomised open-label study with blinded endpoints assessment was performed in 142 patients. Inclusion criteria were hypertension, left ventricular ejection fraction ≥50% and echocardiographic determined LVH, defined as a left ventricular mass index (LVMI) of ≥ 100 g/m(2) in women and ≥ 116 g/m(2) in males. Patients were randomised between rosuvastatin 20mg once daily vs control. For each patient an echocardiogram and blood samples were obtained. These tests were repeated after 6 months. RESULTS: Baseline characteristics: mean age was 62 ± 11year and 62 (44%) were male. In both groups, there was a non-significant reduction in LVMI: 118 ± 22 to 111 ± 19 g/m(2) in the control group and 118 ± 21 to 114 ± 22 in the rosuvastatin group (p=0.376 for the comparison between rosuvastatin and control after 6 months). After six months, LDL-cholesterol was reduced from 3.5 ± 1.0 to 2.1 ± 1.2 mmol/L (40% reduction) in the rosuvastatin group and remained unchanged in the control group (3.5 ± 0.9 vs 3.6 ± 0.9 mmol/L. Hs-CRP decreased more with rosuvastatin compared to control (-38% vs -15%, p=0.006) There was no significant reduction in NT-pro-BNP levels after 6 months. CONCLUSION: Rosuvastatin does not reduce LVH despite a large LDL reduction in patients with hypertension and LVH.

Hypertrophic cardiomyopathy family with double-heterozygous mutations; does disease severity suggest doubleheterozygosity?

Background. With the improvement in genetic testing over time, double-heterozygous mutations are more often found by coincidence in families with hypertrophic cardiomyopathy (HCM). Double heterozygosity can be a cause of the wellknown clinical diversity within HCM families.Methods and results. We describe a family in which members carry either a single mutation or are double heterozygous for mutations in myosin heavy chain gene (MYH7) and cysteine and glycine-rich protein 3 (CSRP3). The described family emphasises the idea of a more severe clinical phenotype with double-heterozygous mutations. It also highlights the importance of cardiological screening where NT-proBNP may serve as an added diagnostic tool.Conclusion. With a more severe inexplicable phenotype of HCM within a family, one should consider the possibility of double-heterozygous mutations. This implies that in such families, even when one disease-causing mutation is found, all the family members still have an implication for cardiological screening parallel to extended genetic screening. (Neth Heart J 2009;17:458-63.).