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Hypertension management in sub-Saharan Africa: an overview of challenges and opportunities for telemedicine
No full textHypertension is the leading contributor to cardiovascular disease (CVD)-related deaths globally, with Africa being one of the World Health Organization regions with the highest prevalence of elevated blood pressure (BP). In sub-Saharan Africa (SSA), awareness, treatment, and control levels of hypertension remain low in both men and women and in different settings, including rural and urban areas. Important barriers to the management of hypertension in SSA are within health systems, usually overburdened by communicable and non-communicable diseases, acute medical conditions, and child and maternal healthcare. Health system-related challenges include the availability and cost of essential medicines and healthcare workforce constraints. At the patient level, individual barriers such as sociodemographic, economic, and psychosocial factors contribute significantly to the poor control of hypertension. Telemedicine presents a promising approach to improve the delivery of optimal care for individuals living with hypertension by serving as a connection between healthcare providers and patients. This may enhance access to isolated people living with hypertension, such as in rural areas. However, there is a concern that telemedicine may exacerbate some of the barriers to the management of hypertension in disadvantaged groups, such as those with limited access to digital technology, low education and literacy levels, and the ageing population. Therefore, the objective of this review is to summarize the current state of telemedicine use in the management of hypertension in SSA and discuss the challenges and opportunities to provide cost-effective, equitable, and sustainable access to digital health technology for people living with hypertension in SSA
Decentralized tracking control design based on intelligent critic for an interconnected spring-mass-damper system
No full textIn this paper, the decentralized tracking control (DTC) problem is investigated for a class of continuous-time nonlinear systems with external disturbances. First, the DTC problem is resolved by converting it into the optimal tracking controller design for augmented tracking isolated subsystems (ATISs).
%It is investigated in the form of the nominal system. A cost function with a discount is taken into consideration. Then, in the case of external disturbances, the DTC scheme is effectively constructed via adding the appropriate feedback gain to each ATIS. %Herein, we aim to obtain the optimal control strategy for minimizing the cost function with discount. In addition, utilizing the approximation property of the neural network, the critic network is constructed to solve the Hamilton-Jacobi-Isaacs equation, which can derive the optimal tracking control law and the worst disturbance law. Moreover, the updating rule is improved during the process of weight learning, which removes the requirement for initial admission control. Finally, through the interconnected spring-mass-damper system, a simulation example is given to verify the availability of the DTC scheme
PANoptosis is a prominent feature of desmoplakin cardiomyopathy
No full textIntroduction: Arrhythmogenic cardiomyopathy (ACM) is hereditary cardiomyopathy caused by pathogenic variants (mutations) in genes encoding the intercalated disc (ID), particularly desmosome proteins. ACM caused by mutations in the DSP gene encoding desmoplakin (DSP) is characterized by the prominence of cell death, myocardial fibrosis, and inflammation, and is referred to as desmoplakin cardiomyopathy.Aim: The aim of this article was to gain insight into the pathogenesis of DSP cardiomyopathy.Methods and Results: The Dsp gene was exclusively deleted in cardiac myocytes using tamoxifen-inducible MerCreMer (Myh6-McmTam) and floxed Dsp (DspF/F) mice (Myh6-McmTam:DspF/F). Recombination was induced upon subcutaneous injection of tamoxifen (30 mg/kg/d) for 5 days starting post-natal day 14. Survival was analyzed by Kaplan-Meier plots, cardiac function by echocardiography, arrhythmias by rhythm monitoring, and gene expression by RNA-Seq, immunoblotting, and immunofluorescence techniques. Cell death was analyzed by the TUNEL assay and the expression levels of specific markers were by RT-PCR and immunoblotting. Myocardial fibrosis was assessed by picrosirius red staining of the myocardial sections, RT-PCR, and immunoblotting. The Myh6-McmTam:DspF/F mice showed extensive molecular remodeling of the IDs and the differential expression of ~10,000 genes, which predicted activation of KDM5A, IRFs, and NFκB and suppression of PPARGC1A and RB1, among others in the DSP-deficient myocytes. Gene set enrichment analysis predicted activation of the TNFα/NFκB pathway, inflammation, cell death programs, and fibrosis. Analysis of cell death markers indicated PANoptosis, comprised of apoptosis (increased CASP3, CASP8, BAD and reduced BCL2), necroptosis (increased RIPK1, RIPK3, and MLKL), and pyroptosis (increased GSDMD and ASC or PYCARD) in the DSP-deficient myocytes. Transcript levels of the pro-inflammatory and pro-fibrotic genes were increased and myocardial fibrosis comprised ~25% of the myocardium in the DSP-deficient hearts. The Myh6-McmTam:DspF/F mice showed severe cardiac systolic dysfunction and ventricular arrhythmias, and died prematurely with a median survival rate of ~2 months.Conclusion: The findings identify PANoptosis as a prominent phenotypic feature of DSP cardiomyopathy and set the stage for delineating the specific molecular mechanisms involved in its pathogenesis. The model also provides the opportunity to test the effects of pharmacological and genetic interventions on myocardial fibrosis and cell death. One sentence summary: Post-natal homozygous deletion of the Dsp gene leads to fulminant PANoptosis and severe myocardial fibrosis, cardiac dysfunction, arrhythmias, and premature death in mice
Organocatalytic Nazarov-type cyclization of 3-alkynyl-2-indolylmethanols: construction of axially chiral cyclopenta[b]indole scaffolds
No full textIn recent years, it has become an urgent task to design new types of indole-based platform molecules for Nazarov-type cyclizations and develop organocatalytic Nazarov-type cyclizations for synthesizing indole derivatives. To fulfill this task, in this work, by changing the alkynyl terminal substituent from t-Bu to an aryl group, the reactivity of 3-alkynyl-2-indolylmethanols is modulated and the new platform molecules serve as competent substrates for Brønsted acid-catalyzed Nazarov-type cyclization. Based on this new reactivity, the first organocatalytic Nazarov-type cyclization of aryl-substituted 3-alkynyl-2-indolylmethanols with 2-naphthols is accomplished, leading to the efficient construction of a new class of axially chiral 3, 4-dihydrocyclopenta[b]indole scaffolds. This preliminary investigation of organocatalytic asymmetric Nazarov-type cyclization provides an optional strategy for the atroposelective construction of this new class of axially chiral cyclopenta[b]indole scaffolds. In addition, the first preparation of axially chiral 3, 4-dihydrocyclopenta[b]indole with optical purity is established through chiral resolution, which could serve as a complementary method to catalytic asymmetric approaches
Machine learning for prediction of postoperative complications after hepato-biliary and pancreatic surgery
No full textDecision making in Hepatobiliary and Pancreatic Surgery is challenging, not least because of the significant complications that may occur following surgery and the complexity of interventions to treat them. Machine Learning (ML) relates to the use of computer derived algorithms and systems to enhance knowledge in order to facilitate decision making and could be of great benefit to surgical patients. ML could be employed pre- or peri-operatively to shape treatment choices prospectively, or could be utilised in the post-hoc analysis of complications in order to inform future practice. ML could reduce errors by drawing attention to known risks of complications through supervised learning, and gain greater insights by identifying previously under-appreciated aspects of care through unsupervised learning. Accuracy, validity and integrity of data are of fundamental importance if predictive models generated by ML are to be successfully integrated into surgical practice. The choice of appropriate ML models and the interface between ML, traditional statistical methodologies and human expertise will also impact the potential to incorporate data science techniques into daily clinical practice
Elastase-dependent congenital neutropenia
No full textCongenital neutropenia, which refers to an inherited deficiency in neutrophils, is a rare pathologic condition that affects approximately 0.0001-0.0009% of the general population. While congenital neutropenia can result from mutations in approximately 30 genes, its leading cause is gain-of-function mutations in the ELANE gene, which encodes the neutrophil granule serine protease, neutrophil elastase. This review focuses on established and novel concepts in the genetic, molecular and cellular mechanisms underlying neutrophil elastase-dependent neutropenia, and discusses possible new avenues for neutropenia research as well as potential novel treatment options that target pathogenic elastase variants
Shape memory behaviors of 3D printed liquid crystal elastomers
No full textAs soft active materials, shape-memory polymers (SMPs) and liquid crystal elastomers (LCEs) have attracted considerable research interest due to their potential applications in various areas. SMPs refer to polymeric materials that can return to their permanent shape in response to external stimuli, such as heat, light, and solvent. In this sense, LCEs can exhibit intrinsic shape-memory behaviors since LCEs can switch between two shapes with temperature change due to the order-disorder transition of liquid crystals. In this work, we fabricate both the polydomain and monodomain nematic LCEs through direct ink writing 3D printing. With increasing the temperature of the substrates, the printed LCEs change from the monodomain state to the polydomain state. For polydomain LCEs, a reversible shape change can occur upon constant loading, while the monodomain can switch the shape with temperature in the stress-free state. This two-way shape-memory behavior is caused by the nematic-isotropic phase transition. We further show that the printed LCEs exhibit a good one-way shape-memory effect due to glass transition. The shape recovery region increases with the programming temperature, which is a typical temperature memory effect. Finally, it is demonstrated that complex shape-memory performance can be designed by combining one-way and two-way shape-memory effects. Specifically, for the monodomain LCEs, with increasing temperature, the programmed shape first recovers, and a second shape change can further occur due to the nematic-isotropic transition
Dissolution and fate of silver nanoparticles in the presence of natural aquatic organic matter
No full textDespite increasing interest in and use of nanoparticles (NP), the environmental consequences of using NP are poorly understood because most relevant studies have not taken the effects of natural coatings on NP into consideration. The aim of this study was to improve our understanding of the fates of NP in aquatic systems. The fates of silver NP (AgNP) capped with citrate and polyethylene glycol dispersed in ecotoxicological matrices in the presence of environmentally relevant components of natural water (humic substances and extracellular polymeric substances) were investigated. Interactions between AgNP and natural organic matter were evaluated by ultracentrifugation and electrophoretic mobility measurements to assess AgNP dissolution. Humic substances and extracellular polymeric substances both decreased the dissolution rate. The natural organic matter (humic substances and extracellular polymeric substances) provided conditions in which the medium stabilized the NP. The dissolution rate depended on the coating type (citrate or polyethylene glycol), dissolved organic carbon concentration, and particle concentration. The presence of algae and Daphnia affected AgNP conversion, demonstrating the value of research that takes environmentally relevant matrices into consideration. The results improve our understanding of the factors that affect the bioavailabilities of AgNP and therefore improve our ability to evaluate AgNP toxicity. Studies of other NP using the same strategy will improve our understanding of the fates of nanomaterials in the environment and biota.Highlights• Natural organic matter controls silver nanoparticle environmental dissolution/fate;• Exopolysaccharides and aquatic humic substances both promote AgNP stabilization;• Capping agents (citrate or polyethylene glycol) change the AgNP dissolution rate;• AgNP behave differently when considering media for algae and Daphnia bioassays
Multi-hazards Shanghai - risk analysis and safety management system
No full textModern cities are prone to various natural and human-made hazards. To deal with these challenges, an effective risk analysis, reduction and management tool is required for all relevant threats. In recent years, a risk analysis and safety management system called the Multi-Hazards Shanghai (MH-SH) system was developed by the Shanghai Institute of Disaster Prevention and Relief to serve the policy makers of government in Shanghai for various disaster decision making of prevention and mitigation. The system can handle various disasters including earthquake, flood, typhoon and man-made fire that affect the operational security of Shanghai. In the paper, the general frame of the MH-SH system was briefly presented. Advanced methodologies and technologies were discussed for their capability of enhancing the platform in multi-disaster monitoring, detection, prediction and management. Finally, the way to the future development of the MH-SH system was concluded
Distal- to- proximal sequential ICG injection technique (DOPSIT) for lymphatic vessels mapping
No full textSupermicrosurgical lymphaticovenular anastomosis (LVA) is the most sought-after procedure among lymphedema patients. However, the same enthusiasm is currently not shared among lymphedema surgeons due to the lackluster results of LVA. The common unfavorable experience with this famed procedure is at least partially caused by the difficulty in finding the lymph vessels. We share our time-tested indocyanine green-based lymph vessel mapping technique, which has helped us establish LVA as our procedure for all fluid-predominant lymphedema
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