Hesperidin, a member of the flavanone group of flavonoids, can be isolated in large amounts from the rinds of some citrus species. Considering the wide range of pharmacological activities and widespread application of hesperidin, this paper reviews preclinical and clinical trials of hesperidin and its related compounds, including their occurrence, pharmacokinetics, and some marketed products available. Preclinical studies and clinical trials demonstrated therapeutical effects of hesperidin and its aglycone hesperetin in various diseases, such as neurological disorders, psychiatric disorders, and cardiovascular diseases and others, due to its anti-inflammatory, antioxidant, lipid-lowering, and insulin-sensitizing properties.
Although stroke incidence in high-income countries (HICs) decreased over the past four decades, it increased dramatically in low- and middle-income countries (LMICs). In this review, we describe the current status of primary prevention, treatment, and management of acute stroke and secondary prevention of and rehabilitation after stroke in LMICs. Although surveillance, screening, and accurate diagnosis are important for stroke prevention, LMICs face challenges in these areas due to lack of resources, awareness, and technical capacity. Maintaining a healthy lifestyle, such as no tobacco use, healthful diet, and physical activity are important strategies for both primary and secondary prevention of stroke. Controlling high blood pressure is also critically important in the general population and in the acute stage of hemorrhagic stroke. Additional primary prevention strategies include community-based education programs, polypill, prevention and management of atrial fibrillation, and digital health technology. For treatment of stroke during the acute stage, specific surgical procedures and medications are recommended, and inpatient stroke care units have been proven to provide high quality care. Patients with a chronic condition like stroke may require lifelong pharmaceutical treatment, lifestyle maintenance and self-management skills, and caregiver and family support, in order to achieve optimal health outcomes. Rehabilitation improves physical, speech, and cognitive functioning of disabled stroke patients. It is expected that home- or community-based services and tele-rehabilitation may hold special promise for stroke patients in LMICs.
Cardiovascular, respiratory, and related disorders (CVRDs) are the leading causes of adult death worldwide, and substantial inequalities in care of patients with CVRDs exist between countries of high income and countries of low and middle income. Based on current trends, the UN Sustainable Development Goal to reduce premature mortality due to CVRDs by a third by 2030 will be challenging for many countries of low and middle income. We did systematic literature reviews of effectiveness and cost-effectiveness to identify priority interventions. We summarise the key findings and present a costed essential package of interventions to reduce risk of and manage CVRDs. On a population level, we recommend tobacco taxation, bans on trans fats, and compulsory reduction of salt in manufactured food products. We suggest primary health services be strengthened through the establishment of locally endorsed guidelines and ensured availability of essential medications. The policy interventions and health service delivery package we suggest could serve as the cornerstone for the management of CVRDs, and afford substantial financial risk protection for vulnerable households. We estimate that full implementation of the essential package would cost an additional US$21 per person in the average low-income country and $24 in the average lower-middle-income country. The essential package we describe could be a starting place for low-income and middle-income countries developing universal health coverage packages. Interventions could be rolled out as disease burden demands and budgets allow. Our outlined interventions provide a pathway for countries attempting to convert the UN Sustainable Development Goal commitments into tangible action.
The cube attack is an important technique for the cryptanalysis of symmetric key primitives, especially for stream ciphers. Aiming at recovering some secret key bits, the adversary reconstructs a superpoly with the secret key bits involved, by summing over a set of the plaintexts/IV which is called a cube. Traditional cube attack only exploits linear/quadratic superpolies. Moreover, for a long time after its proposal, the size of the cubes has been largely confined to an experimental range, e.g., typically 40. These limits were first overcome by the division property based cube attacks proposed by Todo et al. at CRYPTO 2017. Based on MILP modelled division property, for a cube (index set) I, they identify the small (index) subset J of the secret key bits involved in the resultant superpoly. During the precomputation phase which dominates the complexity of the cube attacks, 2 |I|+|J| encryptions are required to recover the superpoly. Therefore, their attacks can only be available when the restriction |I| + |J| < n is met. In this paper, we introduced several techniques to improve the division property based cube attacks by exploiting various algebraic properties of the superpoly.1. We propose the "flag" technique to enhance the preciseness of MILP models so that the proper non-cube IV assignments can be identified to obtain a non-constant superpoly. 2. A degree evaluation algorithm is presented to upper bound the degree of the superpoly. With the knowledge of its degree, the superpoly can be recovered without constructing its whole truth table. This enables us to explore larger cubes I's even if |I| + |J| ≥ n.Corresponding authors.3. We provide a term enumeration algorithm for finding the monomials of the superpoly, so that the complexity of many attacks can be further reduced. As an illustration, we apply our techniques to attack the initialization of several ciphers. To be specific, our key recovery attacks have mounted to 839-round Trivium, 891-round Kreyvium, 184-round Grain-128a and 750-round Acorn respectively.
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