Practical strategies to achieve resilient health systems: results from a scoping review.

BACKGROUND: This paper presents the results of a systematic review to identify practical strategies to create the institutions, skills, values, and norms that will improve health systems resilience. METHODS: A PRISMA 2020 compliant systematic review identified peer-reviewed and gray literature on practical strategies to make health systems more resilient. Investigators screened 970 papers to identify 65 English language papers published since 2015. RESULTS: Practical strategies focus efforts on system changes to improve a health system's resilience components of collective knowing, collective thinking, and collaborative doing. The most helpful studies identified potential lead organizations to serve as the stewards of resilience improvement, and these were commonly in national and local departments of public health. Papers on practical strategies suggested possible measurement tools to benchmark resilience components in efforts to focus on performance improvement and ways to sustain their use. Essential Public Health Function (EPHF) measurement and improvement tools are well-aligned to the resilience agenda. The field of health systems resilience lacks empirical trials linking resilience improvement interventions to outcomes. CONCLUSIONS: The rigorous assessment of practical strategies to improve resilience based on cycles of measurement should be a high priority.

COVID-19 vaccine hesitancy among parents in Low- and Middle-Income Countries: A meta-analysis.

Background: Vaccination is the most effective method to prevent the spread of infectious diseases. Nevertheless, vaccine hesitancy has been an issue. Parental hesitancy toward vaccines is a major part of the problem. COVID-19 vaccine acceptance is no different, it poses another challenge in facing the pandemic. In Low- and Middle-Income Countries (L&MICs) several studies measured parents' acceptance to vaccinate their children against COVID-19 and resulted in different acceptance proportions. Aims: The paper aims at obtaining a precise estimate of the overall proportion of L&MICs' parents accepting to vaccinate their children against COVID-19 and identifying the main determinant of their decisions. Methods: This meta-analysis follows the PRISMA 2020 statement on updated guidelines and the checklist for reporting systematic reviews. Studies published between December till February 2022 were assessed for inclusion. The final effect size (i.e., the proportion of parents in L&MICs accepting to vaccinate their children against COVID-19) was measured using the Arcsine proportions method. Analysis was done using R program. Results: The proportion of parents in L&MICs accepting to vaccinate their children against COVID-19 is 49%. The major reason for their acceptance is their belief that COVID-19 vaccine is fundamental to the fight against the pandemic while the most common factor for parents' hesitancy to vaccinate their children against COVID-19 is their concerns about vaccine efficacy, safety, and possible side effects. Conclusion: The proportion of parents in L&MICs accepting to vaccinate their children against COVID-19 is lower than the global level. To increase parental acceptance, responsible authorities should concentrate on increasing their population's trust in the government and in vaccine manufacturers. As well as concentrating on increasing acceptance of the vaccine idea in general.

RNA Vaccines against Infectious Diseases: Vital Progress with Room for Improvement.

mRNA vaccines have amassed a strong interest from scientists and nonscientists alike for their potential in treating cancer and curbing the spread of infectious diseases. Their success has been bolstered by the COVID-19 pandemic as mRNA vaccines for the SARS-CoV-2 virus showed unrivaled efficiency and success. The strategy relies on the delivery of an RNA transcript that carries the sequence of an antigenic molecule into the body's cells where the antigen is manufactured. The lack of use of infectious pathogens and the fact that they are made of nucleic acids render these vaccines a favorable alternative to other vaccination modalities. However, mRNA vaccination still suffers from a great deal of hurdles starting from their safety, cellular delivery, uptake and response to their manufacturing, logistics and storage. In this review, we examine the premise of RNA vaccination starting from their conceptualization to their clinical applications. We also thoroughly discuss the advances in the field of RNA vaccination for infectious diseases. Finally, we discuss the challenges impeding their progress and shed light on potential areas of research in the field.

Stimuli-Responsive Amphiphilic Pillar[n]arene Nanovesicles for Targeted Delivery of Cancer Drugs.

Cancer chemotherapeutics face several challenges, including uncontrollable drug release, off-target toxic effects, and poor bioavailability. Recently, supramolecular nanovesicles, such as calix[n]arenes (CXs), cyclodextrins (CDs), cucurbiturils (CBs), and pillar[n]arenes (PRs), have attracted attention as potential smart nanocarriers for chemotherapeutics because of their exceptional cavities that can achieve high encapsulation capacity and accommodate both hydrophilic and hydrophobic drugs. In addition, they can be functionalized with different stimuli-responsive groups, which facilitate controlled drug release. Supramolecular nanovesicles, loaded with drugs and decorated with stimuli-responsive targeting moieties, are designed by either host-guest complexation or self-assembly of amphiphilic cavitands. Pillar[n]arenes, in particular, are novel supramolecular host molecules that have recently been employed in cancer targeted drug delivery because of their symmetric pillar-shaped structure, simplicity of functionalization, and biocompatibility. This review summarizes state-of-the-art strategies for developing single or multiple stimuli-responsive pillar[n]arene nanovesicles for effective cancer treatment.

Ethical Dimensions of Public Health Actions and Policies With Special Focus on COVID-19.

During pandemics, the ethicists, public health professionals, and human rights advocates raise a red flag about different public health actions that should, at best, be addressed through integrated, global policies. How to rationalize the healthcare resources and prioritize the cases is not a recent challenge but the serious concern about that is how to achieve this while not increasing the vulnerability of the disadvantaged population. Healthcare professionals use different scoring systems as a part of their decision-making so the medical teams and triage committees can allocate resources for predictable health outcomes and prognosis as well as to appropriately triage the patients accordingly. However, the value of the existing scoring systems to manage COVID-19 cases is not well-established yet. Part of this problem includes managing non-COVID patients with chronic medical conditions like non-communicable diseases and addressing their medical needs during the pandemic complex context in a way to avoid worsening their conditions and, on the other hand, avoid hindering the establishment of comprehensive standards for dealing with COVID-19. In this article, we discuss this dilemma as well as how preexisting ethical standards were challenged by COVID-19. We also discuss how monitoring the consistent application of ethical standards during the medical trials of new medications, vaccines, or unproven medical interventions is also a critical issue.

Peganum harmala Alkaloids Self-Assembled Supramolecular Nanocapsules with Enhanced Antioxidant and Cytotoxic Activities.

Amphiphilic macrocycles, such as p-sulfonatocalix[6]arenes (p-SC6), have demonstrated great potential in designing synthetic nanovesicles based on self-assembly approaches. These supramolecular nanovesicles are capable of improving the solubility, stability, and biological activity of various drugs. In the present study, the biologically active harmala alkaloid-rich fraction (HARF) was extracted from Peganum harmala L. seeds. Ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC/ESI-MS) analysis of HARF revealed 15 alkaloids. The reversed-phase high-performance liquid chromatography (RP-HPLC) analysis revealed three peaks: peganine, harmol, and harmine. The HARF was then encapsulated in p-SC6 nanocapsules employing a thin-film hydration approach. The designed nanocapsules had an average particle size of 264.8 ± 10.6 nm, and a surface charge of -30.3 ± 2.2 mV. They were able to encapsulate 89.3 ± 1.4, 74.4 ± 1.3, and 76.1 ± 1.7% of the three harmala alkaloids; harmine, harmol, and peganine; respectively. The in vitro drug release experiments showed the potential of the designed nanocapsules to release their cargo at a pH of 5.5 (typical of cancerous tissue). The IC50 values of HARF encapsulated in p-SC6 (H/p-SC6 nanocapsules) were 5 and 2.7 µg/mL against ovarian cancer cells (SKOV-3) and breast adenocarcinoma cells (MCF-7), respectively. The prepared nanocapsules were found to be biocompatible when tested on human skin fibroblasts. Additionally, the antioxidant activity of the designed nanocapsules was 5 times that of the free powder fraction; the IC50 of the H/p-SC6 nanocapsules was 30.1 ± 1.3 µg/mL, and that of the HARF was 169.3 ± 7.2 µg/mL. In conclusion, encapsulation of P. harmala alkaloid-rich fraction into self-assembled p-SC6 significantly increases its antioxidant and cytotoxic activities.

Green Synthesis of Platinum and Palladium Nanoparticles Using Peganum harmala L. Seed Alkaloids: Biological and Computational Studies.

This study reports a facile and eco-friendly method for the green synthesis of platinum and palladium nanoparticles (Pt NPs and Pd NPs) using Peganum harmala seed alkaloid fraction. The ζ-potential of the synthesized Pt NPs, Pd NPs and Pt-Pd NPs were -11.2 ± 0.5, -9.7 ±1.2, and -12.7 ± 2.1 mV; respectively. Transmission electron microscopy (TEM) revealed the formation of spherical-shaped nanoparticles with smooth margins. The mean diameters of the synthesized Pt NPs, Pd NPs, and Pt-Pd NPs were determined using TEM analysis and were found to be 20.3 ± 1.9, 22.5 ± 5.7, and 33.5 ± 5.4 nm, respectively. The nanoparticles' bioreduction was confirmed by ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, and their organic contents were determined by thermal gravimetric analysis (TGA). The Pt-Pd NPs mixture showed more pronounced antioxidant activity of 843.0 ± 60 µM Trolox equivalent (TE)/mg NPs compared to the individual Pt NPs (277.3 ± 13.5 µM TE/mg NPs) and Pd NPs (167.6 ± 4.8 µM TE/mg NPs). Furthermore, the Pt-Pd NPs exhibited significant cytotoxic activities against lung cancer (A549) and breast adenocarcinoma (MCF-7) cells, IC50 of 8.8 and 3.6 µg/mL, respectively; as compared to Pt NPs (IC50 of 10.9 and 6.7 µg/mL, respectively) and Pd NPs (IC50 of 31 and 10.8 µg/mL, respectively and compared to carboplatin (IC50 of 23 and 9.5 µg/mL, respectively). Moreover, molecular docking studies were conducted to explore the possible anticancer and antioxidant mechanisms of the biogenic nanoparticles. Pt NPs, Pd NPs, and their mixture showed inhibitory activity against cysteine proteinase, which supports their high antitumor activity, but moderate antioxidant activity. In conclusion, Pd-Pt NPs mixture prepared using harmala seed alkaloid fraction showed potential as effective antineoplastic agents.

COVID-19 Genetic and Environmental Risk Factors: A Look at the Evidence.

The Covid-19 pandemic is with no doubt the biggest health crisis of the 21st century. The disease is caused by a virus of the Coronaviridae family and is closely related to the virus responsible for the severe acute respiratory Syndrome (SARS). Since December 2019, the virus has continued to spread way beyond the location of the first recorded cases (Wuhan, China). As of now, over 5 million cases have been diagnosed with the disease worldwide and over 300 thousand have died. COVID-19 patients suffer from respiratory symptoms that can rapidly turn into potentially fatal acute respiratory distress syndrome (ARDS) in a portion of patients. Although many drugs and vaccines are currently under clinical trials, there is no currently approved treatment or vaccine. It is therefore critical to correctly identify risk factors that lead to the exacerbation of symptoms in highly susceptible groups. Groups that are at high risk include those aged 55 or older especially those with underlying conditions such as cardiovascular diseases. Certain ethnicities such as African-Americans have been found to be at a higher risk and males seem to be higher both in numbers as well as severity of cases. It is hypothesized that these groups are at risk as their molecular landscape is more permissive of viral infection and growth. Different occupations, especially those related to health-care as well as populations that do not cultivate a mask-wearing culture are at higher risk due to environmental exposure. In this article, we examine the evidence regarding different groups that are more sensitive to the disease and review hypotheses pertaining to COVID-19 infection and prognosis. Risk factors that can be related to the molecular landscape of COVID-19 infection as well as those related to environmental and occupational conditions are discussed.