Whom should be saved? A proposed ethical framework for allocating scarce medical resources to COVID-19 patients using fuzzy logic

COVID-19 is a global pandemic that affected the everyday life activities of billions around the world. It is an unprecedented crisis that the modern world had never experienced before. It mainly affected the economic state and the health care system. The rapid and increasing number of infected patients overwhelmed the healthcare infrastructure, which causes high demand and, thus, shortage in the required staff members and medical resources. This shortage necessitates practical and ethical suggestions to guide clinicians and medical centers when allocating and reallocating scarce resources for and between COVID-19 patients. Many studies proposed a set of ethical principles that should be applied and implemented to address this problem. In this study, five different ethical principles based on the most commonly recommended principles and aligned with WHO guidelines and state-of-the-art practices proposed in the literature were identified, and recommendations for their applications were discussed. Furthermore, a recent study highlighted physicians' propensity to apply a combination of more than one ethical principle while prioritizing the medical resource allocation. Based on that, an ethical framework that is based on Fuzzy inference systems was proposed. The proposed framework's input is the identified ethical principles, and the output is a weighted value (per patient). This value can be used as a rank or a priority factor given to the patients based on their condition and other relevant information, like the severity of their disease status. The main idea of implementing fuzzy logic in the framework is to combine more than one principle when calculating the weighted value, hence mimicking what some physicians apply in practice. Moreover, the framework's rules are aligned with the identified ethical principles. This framework can help clinicians and guide them while making critical decisions to allocate/reallocate the limited medical resources during the current COVID-19 crisis and future similar pandemics

Effect of COVID-19 quarantine on the sleep quality and the depressive symptom levels of university students in Jordan during the spring of 2020

Objectives: This study was designed to assess the effect of COVID-19 home quarantine and its lifestyle challenges on the sleep quality and mental health of a large sample of undergraduate University students in Jordan. It is the first study applied to the Jordanian population. The aim was to investigate how quarantine for several weeks changed the students' habits and affected their mental health. Methods: A cross-sectional study was conducted using a random representative sample of 6,157 undergraduate students (mean age 19.79 ± 1.67 years, males 28.7%) from the University of Jordan through voluntarily filling an online questionnaire. The Pittsburgh Sleep Quality Index (PSQI) and the Center for Epidemiologic Studies-Depression Scale (CES-D) were used to assess sleep quality and depressive symptoms, respectively. Results: The PSQI mean score for the study participants was 8.1 ± 3.6. The sleep quality of three-quarters of the participants was negatively affected by the extended quarantine. Nearly half of the participants reported poor sleep quality. The prevalence of poor sleep quality among participants was 76% (males: 71.5% and females: 77.8%). Similarly, the prevalence of the depressive symptoms was 71% (34% for moderate and 37% for high depressive symptoms), with females showing higher prevalence than males. The overall mean CES-D score for the group with low depressive symptoms is 9.3, for the moderate group is 19.8, while it is 34.3 for the high depressive symptoms group. More than half of the students (62.5%) reported that the quarantine had a negative effect on their mental health. Finally, females, smokers, and students with decreased income levels during the extended quarantine were the common exposures that are significantly associated with a higher risk of developing sleep disturbances and depressive symptoms. Conclusions: Mass and extended quarantine succeeded in controlling the spread of the COVID-19 virus; however, it comes with a high cost of potential psychological impacts. Most of the students reported that they suffer from sleeping disorders and had a degree of depressive symptoms. Officials should provide psychological support and clear guidance to help the general public to reduce these potential effects and overcome the quarantine period with minimum negative impacts

Pervasive polymorphic imprinted methylation in the human placenta.

The maternal and paternal copies of the genome are both required for mammalian development, and this is primarily due to imprinted genes, those that are monoallelically expressed based on parent-of-origin. Typically, this pattern of expression is regulated by differentially methylated regions (DMRs) that are established in the germline and maintained after fertilization. There are a large number of germline DMRs that have not yet been associated with imprinting, and their function in development is unknown. In this study, we developed a genome-wide approach to identify novel imprinted DMRs in the human placenta and investigated the dynamics of these imprinted DMRs during development in somatic and extraembryonic tissues. DNA methylation was evaluated using the Illumina HumanMethylation450 array in 134 human tissue samples, publicly available reduced representation bisulfite sequencing in the human embryo and germ cells, and targeted bisulfite sequencing in term placentas. Forty-three known and 101 novel imprinted DMRs were identified in the human placenta by comparing methylation between diandric and digynic triploid conceptions in addition to female and male gametes. Seventy-two novel DMRs showed a pattern consistent with placental-specific imprinting, and this monoallelic methylation was entirely maternal in origin. Strikingly, these DMRs exhibited polymorphic imprinted methylation between placental samples. These data suggest that imprinting in human development is far more extensive and dynamic than previously reported and that the placenta preferentially maintains maternal germline-derived DNA methylation

Differentiation-Dependent Secretion of Proangiogenic Factors by Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are a promising cell population for cell-based bone repair due to their proliferative potential, ability to differentiate into bone-forming osteoblasts, and their secretion of potent trophic factors that stimulate angiogenesis and neovascularization. To promote bone healing, autogenous or allogeneic MSCs are transplanted into bone defects after differentiation to varying degrees down the osteogenic lineage. However, the contribution of the stage of osteogenic differentiation upon angiogenic factor secretion is unclear. We hypothesized that the proangiogenic potential of MSCs was dependent upon their stage of osteogenic differentiation. After 7 days of culture, we observed the greatest osteogenic differentiation of MSCs when cells were cultured with dexamethasone (OM+). Conversely, VEGF protein secretion and upregulation of angiogenic genes were greatest in MSCs cultured in growth media (GM). Using conditioned media from MSCs in each culture condition, GM-conditioned media maximized proliferation and enhanced chemotactic migration and tubule formation of endothelial colony forming cells (ECFCs). The addition of a neutralizing VEGF165/121 antibody to conditioned media attenuated ECFC proliferation and chemotactic migration. ECFCs seeded on microcarrier beads and co-cultured with MSCs previously cultured in GM in a fibrin gel exhibited superior sprouting compared to MSCs previously cultured in OM+. These results confirm that MSCs induced farther down the osteogenic lineage possess reduced proangiogenic potential, thereby providing important findings for consideration when using MSCs for bone repair

Diagnostic implications of pitfalls in causal variant identification based on 4577 molecularly characterized families

Despite large sequencing and data sharing efforts, previously characterized pathogenic variants only account for a fraction of Mendelian disease patients, which highlights the need for accurate identification and interpretation of novel variants. In a large Mendelian cohort of 4577 molecularly characterized families, numerous scenarios in which variant identification and interpretation can be challenging are encountered. We describe categories of challenges that cover the phenotype (e.g. novel allelic disorders), pedigree structure (e.g. imprinting disorders masquerading as autosomal recessive phenotypes), positional mapping (e.g. double recombination events abrogating candidate autozygous intervals), gene (e.g. novel gene-disease assertion) and variant (e.g. complex compound inheritance). Overall, we estimate a probability of 34.3% for encountering at least one of these challenges. Importantly, our data show that by only addressing non-sequencing-based challenges, around 71% increase in the diagnostic yield can be expected. Indeed, by applying these lessons to a cohort of 314 cases with negative clinical exome or genome reports, we could identify the likely causal variant in 54.5%. Our work highlights the need to have a thorough approach to undiagnosed diseases by considering a wide range of challenges rather than a narrow focus on sequencing technologies. It is hoped that by sharing this experience, the yield of undiagnosed disease programs globally can be improved

The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis

OBJECTIVE: To meta-analyse the diagnostic accuracy of US, CT, MRI and (1)H-MRS for the evaluation of hepatic steatosis. METHODS: From a comprehensive literature search in MEDLINE, EMBASE, CINAHL and Cochrane (up to November 2009), articles were selected that investigated the diagnostic performance imaging techniques for evaluating hepatic steatosis with histopathology as the reference standard. Cut-off values for the presence of steatosis on liver biopsy were subdivided into four groups: (1) >0, >2 and >5% steatosis; (2) >10, >15 and >20%; (3) >25, >30 and >33%; (4) >50, >60 and >66%. Per group, summary estimates for sensitivity and specificity were calculated. The natural-logarithm of the diagnostic odds ratio (lnDOR) was used as a single indicator of test performance. RESULTS: 46 articles were included. Mean sensitivity estimates for subgroups were 73.3-90.5% (US), 46.1-72.0% (CT), 82.0-97.4% (MRI) and 72.7-88.5% ((1)H-MRS). Mean specificity ranges were 69.6-85.2% (US), 88.1-94.6% (CT), 76.1-95.3% (MRI) and 92.0-95.7% ((1)H-MRS). Overall performance (lnDOR) of MRI and (1)H-MRS was better than that for US and CT for all subgroups, with significant differences in groups 1 and 2. CONCLUSION: MRI and (1)H-MRS can be considered techniques of choice for accurate evaluation of hepatic steatosi

Contemporary Management of Locally Advanced and Recurrent Rectal Cancer: Views from the PelvEx Collaborative

Pelvic exenteration is a complex operation performed for locally advanced and recurrent pelvic cancers. The goal of surgery is to achieve clear margins, therefore identifying adjacent or involved organs, bone, muscle, nerves and/or vascular structures that may need resection. While these extensive resections are potentially curative, they can be associated with substantial morbidity. Recently, there has been a move to centralize care to specialized units, as this facilitates better multi-disciplinary care input. Advancements in pelvic oncology and surgical innovation have redefined the boundaries of pelvic exenterative surgery. Combined with improved neoadjuvant therapies, advances in diagnostics, and better reconstructive techniques have provided quicker recovery and better quality of life outcomes, with improved survival This article provides highlights of the current management of advanced pelvic cancers in terms of surgical strategy and potential future developments