Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease. HCM is a highly complex and heterogeneous disease regarding not only the number of associated mutations but also ...the severity of phenotype, symptom burden, and the risk of complications, such as heart failure and sudden death. The penetrance is incomplete and it is age and gender dependent. It is accepted as a disease of the sarcomere. Sixty percent of HCM cases carry mutations in 1 of 8 sarcomere protein genes, mainly non‐sense MYBPC3 and missense MYH7 variants. Young patients with severe phenotype and other clinical features are included in proposed scores for prediction of high positive genetic result. The number of genes reported as disease‐causing has increased in the last few years, in some cases without robust evidence. Currently available in silico tools are not always useful for differentiation between benign and deleterious variants. There is enough information on genotype‐phenotype correlations to start understanding the mechanisms of the disease. Genetic and environmental modifiers have been explored with some interesting insights from miRNA studies with potential as biomarkers and therapeutic agents. There is an additional value of genetic testing in HCM for prognosis. Knowledge about genetics and functional studies are the basis of near future therapies.
Objectives
To review the impact of social isolation during COVID-19 pandemic on mental and physical health of older people and the recommendations for patients, caregivers and health professionals.
...Design
Narrative review.
Setting
Non-institutionalized community-living people.
Participants
20.069 individuals from ten descriptive cross-sectional papers.
Measurements
Articles since 2019 to 2020 published on Pubmed, Scielo and Google Scholar databases with the following MeSh terms (‘COVID-19’, ‘coronavirus’, ‘aging’, ‘older people’, ‘elderly’, ‘social isolation’ and ‘quarantine’) in English, Spanish or Portuguese were included. The studies not including people over 60 were excluded. Guidelines, recommendations, and update documents from different international organizations related to mental and physical activity were also analysed.
Results
41 documents have been included in this narrative review, involving a total of 20.069 individuals (58% women), from Asia, Europe and America. 31 articles included recommendations and 10 addressed the impact of social distancing on mental or physical health. The main outcomes reported were anxiety, depression, poor sleep quality and physical inactivity during the isolation period. Cognitive strategies and increasing physical activity levels using apps, online videos, telehealth, are the main international recommendations.
Conclusion
Mental and physical health in older people are negatively affected during the social distancing for COVID-19. Therefore, a multicomponent program with exercise and psychological strategies are highly recommended for this population during the confinement. Future investigations are necessary in this field.
Pathologists face a substantial increase in workload and complexity of histopathologic cancer diagnosis due to the advent of personalized medicine. Therefore, diagnostic protocols have to focus ...equally on efficiency and accuracy. In this paper we introduce 'deep learning' as a technique to improve the objectivity and efficiency of histopathologic slide analysis. Through two examples, prostate cancer identification in biopsy specimens and breast cancer metastasis detection in sentinel lymph nodes, we show the potential of this new methodology to reduce the workload for pathologists, while at the same time increasing objectivity of diagnoses. We found that all slides containing prostate cancer and micro- and macro-metastases of breast cancer could be identified automatically while 30-40% of the slides containing benign and normal tissue could be excluded without the use of any additional immunohistochemical markers or human intervention. We conclude that 'deep learning' holds great promise to improve the efficacy of prostate cancer diagnosis and breast cancer staging.
The aim of this study was to clarify which cognitive mechanisms underlie Trail Making Test (TMT) direct and derived scores. A comprehensive review of the literature on the topic was carried out to ...clarify which cognitive factors had been related to TMT performance. Following the review, we explored the relative contribution from working memory, inhibition/interference control, task-switching ability, and visuomotor speed to TMT performance. Forty-one healthy old subjects participated in the study and performed a battery of neuropsychological tests including the TMT, the Digit Symbol subtest Wechsler Adult Intelligence Scale (Third Version) (WAIS-III), a Finger Tapping Test, the Digits Forward and Backward subtests (WAIS-III), Stroop Test, and a task-switching paradigm inspired in the Wisconsin Card Sorting Test. Correlation and regression analyses were used in order to clarify the joint and unique contributions from different cognitive factors to the prediction of TMT scores. The results suggest that TMT-A requires mainly visuoperceptual abilities, TMT-B reflects primarily working memory and secondarily task-switching ability, while B-A minimizes visuoperceptual and working memory demands, providing a relatively pure indicator of executive control abilities.
Targeting cell cycle has become one of the major challenges in cancer therapy, being Palbociclib, a CDK4/6 inhibitor, an excellent example. Recently, it has been reported that Palbociclib could be a ...novel radiosensitizer agent. In an attempt to clarify the molecular basis of this effect we have used cell lines from colorectal (HT29, HCT116) lung (A549, H1299) and breast cancer (MCF-7). Our results indicate that the presence of a p53 wild type is strictly required for Palbociclib to exert its radiosensitizing effect, independently of the inhibitory effect exerted on CDK4/6. In fact, abrogation of p53 in cells with functional p53 blocks the radiosensitizing effect of Palbociclib. Moreover, no radiosensitizing effect is observed in cells with non-functional p53, but restoration of p53 function promotes radiosensitivity associated to Palbociclib. Furthermore, the presence of Palbociclib blocks the transcriptional activity of p53 in an ATM-dependent-fashion after ionizing radiation exposure, as the blockage of p21/WAF1 expression demonstrates. These observations are a proof of concept for a more selective therapy, based on the combination of CDK4/6 inhibition and radiotherapy, which would only benefit to those patients with a functional p53 pathway.
•Palbociclib promotes radiosensitivity in lung and colon cancer derived cell lines.•Palbociclib promotes radiosensitivity independently of CDk4/6 chemical inhibition.•Palbociclib associated radiosensitivity requires a functional p53 signalling.•P53 could be a novel biomarker for the combination of Palbociclib and radiotherapy.
•A system based on deep learning is shown to outperform a state-of-the art CAD system.•Adding complementary handcrafted features to the CNN is shown to increase performance.•The system based on deep ...learning is shown to perform at the level of a radiologist.
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Recent advances in machine learning yielded new techniques to train deep neural networks, which resulted in highly successful applications in many pattern recognition tasks such as object detection and speech recognition. In this paper we provide a head-to-head comparison between a state-of-the art in mammography CAD system, relying on a manually designed feature set and a Convolutional Neural Network (CNN), aiming for a system that can ultimately read mammograms independently. Both systems are trained on a large data set of around 45,000 images and results show the CNN outperforms the traditional CAD system at low sensitivity and performs comparable at high sensitivity. We subsequently investigate to what extent features such as location and patient information and commonly used manual features can still complement the network and see improvements at high specificity over the CNN especially with location and context features, which contain information not available to the CNN. Additionally, a reader study was performed, where the network was compared to certified screening radiologists on a patch level and we found no significant difference between the network and the readers.
Lateral ridge augmentation procedures are aimed to reconstruct deficient alveolar ridges or to build up peri-implant dehiscence and fenestrations. The objective of this systematic review was to ...assess the efficacy of these interventions by analyzing data from 40 clinical studies evaluating bone augmentation through either the staged or the simultaneous approach. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guideline for systematic reviews was used. The primary outcomes were the changes at reentry, in the ridge width, and in the vertical and horizontal dimensions of the peri-implant defect, measured in millimeters, in the staged and simultaneous approaches, respectively. The results of the meta-analysis showed, for the simultaneous approach, a statistically significant defect height reduction when all treatments were analyzed together (weighted mean difference WMD = −4.28 mm; 95% confidence interval: CI –4.88, –3.69; P < 0.01). The intervention combining bone replacement grafts with barrier membranes was associated with superior outcomes The most frequently used intervention was the combination of xenograft and bioabsorbable membrane. Similarly, for the staged approach, there was a statistically significant horizontal gain when all treatment groups were combined (WMD = 3.90 mm; 95% CI: 3.52, 4.28; P < 0.001). The most frequently used intervention was the use of autogenous bone blocks. Both treatment strategies led to high survival and success rates (>95%) for the implants placed on the regenerated sites. Nonexposed sites gained significantly more in the simultaneous and staged approaches (WMD = 1.1 and 3.1 mm).
The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary ...theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches.
Introduction
Lurasidone is an atypical antipsychotic used in the treatment of schizophrenia and bipolar depression. Both indications are approved by the FDA nowadays, whereas in Europe it is only ...approved for schizophrenia. Lurasidone has been barely studied for the treatment of acute mania, nonetheless it is sometimes used off-label.
Objectives
A case of a patient with a manic episode treated with lurasidone is presented, in order to provide further evidence on this topic.
Methods
The patient is a 43 year-old-woman with diagnosis of type I bipolar disorder, personality disorder and borderline intellectual functioning, resident in our Hospital’s long-stay psychiatric rehabilitation unit. She was previously under treatment with venlafaxine 75 mg/day, valproate 1500 mg/day and levomepromazine 25 mg on demand; remaining stable for months. The patient presented an episode consisting on agitation, irritability, verbiage, tachyphase, verbal aggressiveness and behavioral disturbances. Psysical restraint was needed for one day long and zuclopenthixol acetate 50 mg IM was administered twice within 5 days for the acute agitation. Venlafaxine was immediately withdrawn and lurasidone was progressively introduced up to 111 mg daily.
Results
Approximately 3 weeks after the treatment adjustment, the patient reached the psychopatological stabilty.
Conclusions
Antidepressive withdrawal and introduction of Lurasidone were effective to treat the acute manic episode in this patient. It has been previosuly suggested that lurasidone caused improvement in emergent manic symptoms in patients with bipolar depression, and in subsyndromal hypomanic symptoms in patients with mixed features of depression. However, no studies have been made yet to evaluate the efficacy of lurasidone in acute mania.
Disclosure
I received financing from Angelini Pharma, Casen Recordati, Janssen, Exeltis and Otsuka.
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