Kolaviron neuroprotective effect against okadaic acid-provoked cognitive impairment.

Alzheimer's disease (AD) is acknowledged as the main causative factor of dementia that affects millions of people around the world and is increasing at increasing pace. Okadaic acid (OA) is a toxic compound with ability to inhibit protein phosphatases and to induce tau protein hyperphosphorylation and Alzheimer's-like phenotype. Kolaviron (KV) is a bioflavonoid derived from Garcinia kola seeds with anti-antioxidative and anti-inflammation properties. The main goal of this study was to assess whether kolaviron can exert neuroprotective effect against okadaic acid-induced cognitive deficit. Rats had an intracerebroventricular (ICV) injection of OA and pretreated with KV at 50 or 100 mg/kg and examined for cognition besides histological and biochemical factors. OA group treated with KV at 100 mg/kg had less memory deficit in passive avoidance and novel object discrimination (NOD) tasks besides lower hippocampal levels of caspases 1 and 3, tumor necrosis factor α (TNFα) and interleukin 6 (IL-6) as inflammatory factors, reactive oxygen species (ROS), protein carbonyl, malondialdehyde (MDA), and phosphorylated tau (p-tau) and higher level of acetylcholinesterase (AChE) activity, mitochondrial integrity index, superoxide dismutase (SOD), and glutathione (GSH). Moreover, KV pretreatment at 100 mg/kg attenuated hippocampal CA1 neuronal loss and glial fibrillary acidic protein (GFAP) reactivity as a factor of astrogliosis. In summary, KV was able to attenuate cognitive fall subsequent to ICV OA which is partly mediated through its neuroprotective potential linked to mitigation of tau hyperphosphorylation, apoptosis, pyroptosis, neuroinflammation, and oxidative stress and also improvement of mitochondrial health.

Cost-effectiveness of remdesivir for the treatment of hospitalized patients with COVID-19: a systematic review.

BACKGROUND: Remdesivir is being studied and used to treat coronavirus disease 2019 (COVID-19). This study aimed to systematically identify, critically evaluate, and summarize the findings of the studies on the cost-effectiveness of remdesivir in the treatment of hospitalized patients with COVID-19. METHODS: In this systematic review, PubMed, EMBASE, Web of Science, SCOPUS, and the Cochrane Library were searched for studies published between 2019 and 2022. We included all full economic evaluations of remdesivir for the treatment of hospitalized patients with COVID-19. Data were summarized in a structured and narrative manner. RESULTS: Out of 616 articles obtained in this literature search, 12 studies were included in the final analysis. The mean score of the Quality of Health Economic Studies (QHES) for the studies was 87.66 (high quality). All studies were conducted in high-income countries (eight studies in the USA and one study in England), except for three studies from middle-to-high-income countries (China, South Africa, and Turkey). Six studies conducted their economic analysis in terms of a health system perspective; five studies conducted their economic analysis from a payer perspective; three studies from the perspective of a health care provider. The results of five studies showed that remdesivir was cost-effective compared to standard treatment. Furthermore, the therapeutic strategy of combining remdesivir with baricitinib was cost-effective compared to remdesivir alone. CONCLUSIONS: Based on the results of the present study, remdesivir appears to be cost-effective in comparison with the standard of care in China, Turkey, and South Africa. Studies conducted in the United States show conflicting results, and combining remdesivir with baricitinib is cost-effective compared with remdesivir alone. However, the cost-effectiveness of remdesivir in low-income countries remains unknown. Thus, more studies in different countries are required to determine the cost-effectiveness of this drug.

Cost Effectiveness of Adding Dapagliflozin to Standard Care in Heart Failure Patients with Reduced Ejection Fraction: A Systematic Review.

INTRODUCTION: Dapagliflozin, a new treatment option for heart failure, leads to a significant reduction in the hospitalization of patients with heart failure. We aimed to review studies on the economic evaluation of adding dapagliflozin to standard care compared with standard care alone in heart failure patients with reduced ejection fraction (HFrEF). METHODS: For this systematic review, the PubMed, EMBASE, Web of Science, Cochrane, Scopus, and CEA Registry scientific databases were searched from 1 January 2020 to 25 March 2022. Two of the present researchers screened titles and abstracts, extracted data from full-text articles, and evaluated their quality using the Quality of Health Economic Studies (QHES) checklist for the quality assessment of health economic studies. RESULTS: Of the 456 abstracts screened, 19 studies met the inclusion criteria. The mean QHES score for the studies was 0.87 (high quality). Eight studies on cost-effectiveness analysis, ten studies on cost-utility analysis, and one study on cost-minimization analysis were conducted. Based on the available evidence and the present findings, the addition of dapagliflozin to standard care in patients with HFrEF was cost effective in most countries. CONCLUSIONS: Based on the results of the present study, the addition of dapagliflozin to standard care in patients with HFrEF was cost effective. More studies investigating the cost effectiveness of dapagliflozin in patients with HFrEF are required in light of the actual epidemiological data of countries in the relevant input parameters. It is also recommended to conduct cost-effectiveness studies of dapagliflozin taking into account costs and benefits from a societal perspective.

Economic evaluation of ferric carboxymaltose compared with placebo in iron-deficient patients with heart failure: a systematic review.

BACKGROUND: It has been shown that ferric carboxymaltose (FCM) improves symptoms and quality of life in iron-deficient patients with heart failure (HF). AIM: We aimed to systematically review studies conducted on the cost-effectiveness of FCM compared to placebo in iron-deficient patients with HF. METHOD: We searched PubMed, EMBASE, Scopus, and Web of Science to find the relevant studies. After removing duplicates, two authors independently evaluated the titles, abstracts, and full texts. We included studies that investigated the full economic evaluations of FCM in HF patients with iron deficiency (cost-effectiveness analysis, cost-utility analysis, and cost-benefit analysis) and used the CHEERS tool to evaluate the quality of the studies. RESULTS: Seven studies were included which evaluated the economic analysis of treatments with FCM in iron-deficient patients with HF. The CHEERS scores for most of the studies (n = 6) were 0.77 or higher (very good quality). The lowest incremental cost-effectiveness ratio (ICER) per quality-adjusted life years (QALY) of FCM ($1801.96) was from Italy, and the highest ICER per QALY of FCM ($25,981.28) South Korea. Results of the studies showed that FCM, compared to placebo, was cost-effective in iron-deficient patients with HF. CONCLUSION: FCM is a cost-effective treatment for iron-deficient patients with HF. Considering the fact that all the included studies in the present systematic review took place in high-income countries, we recommend further studies investigating the cost-effectiveness of FCM in low- and middle-income countries.

Acetyl-L-Carnitine Exerts Neuroprotective and Anticonvulsant Effect in Kainate Murine Model of Temporal Lobe Epilepsy.

The most well-known type of focal epilepsy that is resistant to existing treatments is temporal lobe epilepsy (TLE), with seizure foci in various structures including temporal lobe, hippocampus, amygdala, entorhinal cortex, and subcortex. The most significant processes involved in the pathophysiology of temporal lobe epilepsy (TLE) are oxidative stress, inflammation, and pyroptosis. There are evidences indicating that acetyl-l-carnitine (ALC) has anti-oxidative, anti-inflammatory, and anti-pyroptotic effects. In the present study, rat model of TLE was induced by intrahippocampal kainate and animals received ALC (100 mg/kg, p.o.). ALC properly attenuated intensity of seizures and also incidence of kainate-induced status epilepticus (SE). As well, obtained findings showed that ALC can partially reverse hippocampal levels of MDA, ROS, SOD, TNFa, NF-kB, TLR4, GFAP, and caspase 1. Besides, treatment of kainate group with ALC exerted a protective effect against CA1 neuronal loss and abnormal mossy fiber sprouting (MFS). Conclusively, these results suggest that ALC is capable to attenuate kainate-induced SE which is somewhat mediated through its lowering of oxidative stress, neuroinflammation, and pyroptosis that are related to its neuroprotective effect.

Will carbon nanotube/nanofiber bring new hope for the treatment of heart damage? A systematic review.

Aim: Despite scientific advances, the number of cardiovascular patients is increasing worldwide. To protect damaged cardiomyocytes from further harm, novel and safer approaches are needed to help regeneration and prevent fibrosis. Methods: In this study, we performed a systematic review of in vitro and preclinical studies of carbon nanotubes (CNTs) and carbon nanofibers (CNFs) for help to treat heart damage. Conclusion: CNTs/CNFs in hydrogels cause higher conductivity, and the in case of alignment this increase is more than the random state. CNTs/CNFs can improve structural specification of the hydrogel for cardiac cell proliferation and enhance expression of genes associated with final differentiation of various stem cells to cardiac cells.

Despite scientific advances, the number of cardiovascular patients is increasing worldwide, and unfortunately, no solution has been provided to protect patients from further damage after ischemia. The heart, unlike many tissues in the human body, lacks the ability to regenerate after damage. To protect damaged heart cells from further damage as well as to grow new heart cells, newer and safer approaches are needed to help reconstruction. In this study, we conducted a systematic review of in vitro studies and animal models of heart attack that have used carbon nanotubes and carbon nanofibers to treat heart damage. The results showed these nanomaterials increase the conductivity of the material in which they are mixed and change the structural characteristics in a way that increases the proliferation of heart cells and causes the differentiation into cardiac cells. It also helps to repair the damaged area of the heart after myocardial ischemia.

Prevalence of depression, anxiety, and psychological distress in patients with epilepsy during COVID-19: A systematic review.

OBJECTIVE: COVID-19 pandemic disease has profound consequences for physical and mental health. In this regard, health care for chronic diseases, especially epilepsy is neglected The purpose of this systematic review study was to investigate the epidemic effect of COVID-19 on increasing the prevalence of mental disorders such as depression, anxiety, and sleep disorders in people with epilepsy (PWE). METHODS: We systematically searched MEDLINE, Cochrane, Embase, Web of science, Scopus, and Psych info databases for studies that estimate the prevalence of mental disorders in PWE during the COVID-19 until December 2020. Inclusion criteria included samples of population, with a confirmed diagnosis of epilepsy. RESULTS: Irrespective of PWE or people without epilepsy (PWOE), all experienced stress and anxiety during COVID-19 pandemic. Most of the studies showed that PWE and even PWOE during the pandemic, suffer from depression. The highest rate of depression was attributed to female PWE with financial problems (66.7%) and the lowest rate of depression in PWE was reported in 8.6%. 7.1-71.2% and 28.2% of patients reported sleep disorders and insomnia, respectively. Less than 2% experienced a sleep improvement. LIMITATIONS: Due to a large amount of heterogeneities across the results, we could not evaluate the exact rate of prevalence in spite of using effective measures. CONCLUSIONS: People with epilepsy were considered as a susceptible group to the impact of the pandemic. Therefore, great attention should be paid to PWE and adequate psychological supports provided in this period to relieve or inhibit risks to mental health in PWE.

Sinomenine Alleviates Murine Experimental Autoimmune Encephalomyelitis Model of Multiple Sclerosis through Inhibiting NLRP3 Inflammasome.

Multiple sclerosis (MS) is known as a chronic neuroinflammatory disorder typified by an immune-mediated demyelination process with ensuing axonal damage and loss. Sinomenine is a natural alkaloid with different therapeutic benefits, including anti-inflammatory and immunosuppressive activities. In this study, possible beneficial effects of sinomenine in an MOG-induced model of MS were determined. Sinomenine was given to MOG35-55-immunized C57BL/6 mice at doses of 25 or 100 mg/kg/day after onset of MS clinical signs till day 30 post-immunization. Analyzed data showed that sinomenine reduces severity of the clinical signs and to some extent decreases tissue level of pro-inflammatory cytokines IL-1ß, IL-6, IL-18, TNFα, IL-17A, and increases level of anti-inflammatory IL-10. In addition, sinomenine successfully attenuated tissue levels of inflammasome NLRP3, ASC, and caspase 1 besides its reduction of intensity of neuroinflammation, demyelination, and axonal damage and loss in lumbar spinal cord specimens. Furthermore, immunoreactivity for MBP decreased and increased for GFAP and Iba1 after MOG-immunization, which was in part reversed upon sinomenine administration. Overall, sinomenine decreases EAE severity, which is attributed to its alleviation of microglial and astrocytic mobilization, demyelination, and axonal damage along with its suppression of neuroinflammation, and its beneficial effect is also associated with its inhibitory effects on inflammasome and pyroptotic pathways; this may be of potential benefit for the primary progressive phenotype of MS.

Economic evaluation of programs against COVID-19: A systematic review.

BACKGROUND: The COVID-19 pandemic has become a public health emergency and raised global concerns in about 213 countries without vaccines and with limited medical capacity to treat the disease. The COVID-19 has prompted an urgent search for effective interventions, and there is little information about the money value of treatments. The present study aimed to summarize economic evaluation evidence of preventing strategies, programs, and treatments of COVID-19. MATERIAL AND METHODS: We searched Medline/PubMed, Cochrane Library, Web of Science Core Collection, Embase, Scopus, Google Scholar, and specialized databases of economic evaluation from December 2019 to July 2020 to identify relevant literature to economic evaluation of programs against COVID-19. Two researchers screened titles and abstracts, extracted data from full-text articles, and did their quality assessment by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Then, quality synthesis of results was done. RESULTS: Twenty-six studies of economic evaluations met our inclusion criteria. The CHEERS scores for most studies (n = 9) were 85 or higher (excellent quality). Eight studies scored 70 to 85 (good quality), eight studies scored 55 to 70 (average quality), and one study < %55 (poor quality). The decision-analytic modeling was applied to twenty-three studies (88%) to evaluate their services. Most studies utilized the SIR model for outcomes. In studies with long-time horizons, social distancing was more cost-effective than quarantine, non-intervention, and herd immunity. Personal protective equipment was more cost-effective in the short-term than non-intervention. Screening tests were cost-effective in all studies. CONCLUSION: The results suggested screening tests and social distancing to be cost-effective alternatives in preventing and controlling COVID-19 on a long-time horizon. However, evidence is still insufficient and too heterogeneous to allow any definite conclusions regarding costs of interventions. Further research as are required in the future.

Conductive carbon nanofibers incorporated into collagen bio-scaffold assists myocardial injury repair.

Currently, treatment of myocardial infarction considered as unmet clinical need. Nanomaterials have been used in the regeneration of tissues such as bone, dental and neural tissue in the body and have increased hope for revitalizing of damaged tissues. Conductive carbon base nanomaterials with its superior physicochemical properties have emerged as promising materials for cardiovascular application. In this study, we applied a biosynthetic collagen scaffold containing carbon nanofiber for regenerating of damaged heart tissue. The collagen-carbon nanofiber scaffold was fabricated and fully characterised. The scaffold was grafted on the affected area of myocardial ischemia, immediately after ligation of the left anterior descending artery in the wistar rat's model. After 4 weeks, histological analyses were performed for investigation of formation of immature cardio-myocytes, epicardial cells, and angiogenesis. Compared to untreated hearts, this scaffold significantly protects heart tissue against injury. This improvement is accompanied by a reduction in fibrosis and the increased formation of a blood vessel network and immature cardio-myocytes in the infarction heart. No toxicity detected with apoptotic and TUNEL assays. In conclusion, the mechanical support of the collagen scaffold with carbon nanofiber enhanced the regeneration of myocardial tissue.

Neuroprotective and anticonvulsant effects of sinomenine in kainate rat model of temporal lobe epilepsy: Involvement of oxidative stress, inflammation and pyroptosis.

Oxidative stress, inflammation and pyroptosis are three of the most important mechanisms in the pathophysiology of temporal lobe epilepsy (TLE). Most people with TLE are refractory to the existing drugs. Sinomenine has shown neuroprotective effects through counteracting oxidative stress, inflammation and pyroptosis. In this study, we evaluated the effect of sinomenine on seizure behavior, oxidative stress, inflammation and pyroptosis markers in addition to its neuroprotective potential in intrahippocampal kainate-induced rat model of TLE. For this purpose, male rats (n = 60) were randomly divided into five groups, i.e., sham, kainate (lesion) with an intrahippocampal injection of kainate, kainate groups receiving sinomenine at doses of 30 or 50 mg/kg, and kainate group receiving valproic acid at a dose of 200 mg/kg (as the positive control). Our obtained data showed that sinomenine administration at a dose of 50 mg/kg can significantly decreases severity of seizures and incidence of status epilepticus (SE), hippocampal aberrant MFS and DNA fragmentation and prevents reduction of neuronal density. It also significantly restored level of ROS, MDA, HO-1 and SOD but its effect on GSH level was not significant. Additionally, sinomenine at a dose of 50 mg/kg partially counteracted the increase of NF-κB, TLR 4, TNFα, GFAP and caspase 1. These results suggest that sinomenine has anticonvulsant and neuroprotective effects by reducing hippocampal oxidative stress, inflammation, pyroptosis and apoptosis in intrahippocampal kainate model of TLE.