Monoterpenes as a perspective for the treatment of seizures: A Systematic Review

BackgroundEpilepsy affects more than 65 million people worldwide. Treatment for epileptic seizures is ineffective and has many adverse effects. For this reason, the search for new therapeutic options capable of filling these limitations is necessary.Hypothesis/PurposeIn this sense, natural products, such as monoterpenes, have been indicated as a new option to control neurological disorders such as epilepsy.Study DesignTherefore, the objective of this study was to review the monoterpenes that have anticonvulsive activity in animal models.MethodsThe searches were performed in the PubMed, Web of Science and Scopus databases in September, 2020 and compiled studies using monoterpenes as an alternative to seizure. Two independent reviewers performed the study selection, data extraction and methodological quality assessment using the Syrcle tool.Results51 articles that described the anticonvulsant activity of 35 monoterpenes were selected with action on the main pharmacological target, including GABAA receptors, glutamate, calcium channels, sodium and potassium. In addition, these compounds are capable of reducing neuronal inflammation and oxidative stress caused by seizure.ConclusionThese compounds stand out as a promising alternative for acting through different pharmacological mechanisms, which may not only reduce seizure, but also promote neuroprotective effect by reducing toxicity in brain regions. However, further studies are needed to determine the mechanism of action and safety assessment of these compounds.     

Cadmium and cardiovascular diseases: cell biology,pathophysiology, and epidemiological relevance

Today cardiovascular diseases (CVDs) are the killer number one world wide. In 2004 an estimated 17.1 million people died due to CVDs and this number will further increase to an estimated 23.6 million by 2030. Importantly, currently known risk factors, like hypertension, and hypercholesterolemia, can only be made responsible for about 50–75% of all CVDs, highlighting the urgent need to search for and define new CVD risk factors. Cadmium (Cd) was shown to have the potential to serve as one such novel risk factor, as it was demonstrated—in vitro, in animal studies, and in human studies—that Cd causes atherosclerosis (the basis of most CVDs). Herein, we discuss the molecular and cellular biological effects of Cd in the cardiovascular system; we present concepts on the pathophysiology of Cd-caused atherosclerosis, and provide data that indicate an epidemiological relevance of Cd as a risk factor for CVDs.     

Zinc supplementation and cardiovascular disease risk factors: A GRADE-assessed systematic review and dose-response meta-analysis

Background and objectiveA deficit in zinc has been related to a higher probability of developing cardiovascular diseases (CVDs). The anti-inflammatory and anti-oxidative capabilities of zinc may have a wide range of therapeutic impacts on CVDs. We conducted a comprehensive systematic review and meta-analysis of the possible impacts that zinc supplementation may have on the risk factors associated with CVDs.MethodsTo identify eligible randomized clinical trials (RCTs) evaluating the effects of zinc supplementation on CVDs risk factors, electronic databases including PubMed, Web of Science, and Scopus were systematically searched up to January 2023. The heterogeneity of trials was checked using the I² statistic. According to the heterogeneity tests, random effects models were estimated and pooled data were defined as the weighted mean difference (WMD) with a 95% confidence interval (CI).ResultsOf 23165 initial records, 75 studies that met inclusion criteria were analyzed in this meta-analysis. The pooled findings indicated the significant lowering effects of zinc supplementation on triglycerides (TG), total cholesterol (TC), fasting blood glucose (FBG), Hemoglobin A1C (HbA1C), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), C-reactive protein (CRP), interleukin-6 (IL-6), Tumor necrosis factor-α (TNF-α), nitric oxide (NO), malondialdehyde (MDA), total antioxidant capacity (TAC), and glutathione (GSH), with no noticeable effects on low-density lipoprotein (LDL), high-density lipoprotein (HDL), insulin, systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate transaminase (AST), and Alanine aminotransferase (ALT).ConclusionOverall, zinc supplementation may boost recognized coronary risk factors that contribute to the development of CVDs. Future research should be conducted to bolster our results.     

Current Prevalence Pattern of Hypertension in Nigeria: A Systematic Review

BackgroundThe global burden of hypertension and other non-communicable diseases (NCDs) is rapidly increasing, and the African continent seems to be the most affected region in the world. The prevalence of hypertension in Nigeria forms a substantial portion of the total burden in Africa because of the large population of the country currently estimated to be over 170 million.ObjectiveThe purpose of this systematic review is to summarise up to date data on the prevalence and distribution of hypertension in Nigeria from prevalence studies.MethodsA search of the following databases: PubMed, EMBase and WHO cardiovascular InfoBase from 1968 till date was conducted to identify studies which provide estimates of prevalence of hypertension in Nigeria.ResultsThe search yielded a total of 1748 hits from which 45 relevant studies met the inclusion criteria for the review. The overall crude prevalence of hypertension ranged from 0.1% (95%CI:-0.1 to 0.3) to 17.5% (95% CI: 13.6 to 21.4) in children and 2.1% (95%CI: 1.4 to 2.8) to 47.2% (95%CI: 43.6 to 50.8) in adults depending on the benchmark used for diagnosis of hypertension, the setting in which the study was conducted, sex and ethnic group. The crude prevalence of hypertension ranged from 6.2% (95%CI: 4.0 to 8.4) to 48.9% (95%CI: 42.3 to 55.5) for men and 10% (95%CI: 8.1 to 12) to 47.3% (95%CI: 43 to 51.6%) for women. In most studies, prevalence of hypertension was higher in males than females. In addition, prevalence across urban and rural ranged from 9.5% (95%CI: 13.6 to 21.4) to 51.6% (95%CI: 49.8 to 53.4) and 4.8% (95%CI: 2.9 to 6.7) to 43% (95%CI: 42.1 to 43.9) respectively.ConclusionsThe prevalence of hypertension is high among the Nigerian population. Appropriate interventions need to be developed and implemented to reduce the preventable burden of hypertension especially at Primary Health Care Centres which is the first point of call for over 55% of the Nigerian population.     

Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review

ObjectiveOptimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19.MethodsA systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for “steroid-induced diabetes” or “steroid-induced hyperglycemia.” Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality.ResultsInitial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19–related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens.ConclusionFew RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.     

Dissemination Bias in Systematic Reviews of Animal Research: A Systematic Review

Background

Systematic reviews of preclinical studies, in vivo animal experiments in particular, can influence clinical research and thus even clinical care. Dissemination bias, selective dissemination of positive or significant results, is one of the major threats to validity in systematic reviews also in the realm of animal studies. We conducted a systematic review to determine the number of published systematic reviews of animal studies until present, to investigate their methodological features especially with respect to assessment of dissemination bias, and to investigate the citation of preclinical systematic reviews on clinical research.

Methods

Eligible studies for this systematic review constitute systematic reviews that summarize in vivo animal experiments whose results could be interpreted as applicable to clinical care. We systematically searched Ovid Medline, Embase, ToxNet, and ScienceDirect from 1^st January 2009 to 9^th January 2013 for eligible systematic reviews without language restrictions. Furthermore we included articles from two previous systematic reviews by Peters et al. and Korevaar et al.

Results

The literature search and screening process resulted in 512 included full text articles. We found an increasing number of published preclinical systematic reviews over time. The methodological quality of preclinical systematic reviews was low. The majority of preclinical systematic reviews did not assess methodological quality of the included studies (71%), nor did they assess heterogeneity (81%) or dissemination bias (87%). Statistics quantifying the importance of clinical research citing systematic reviews of animal studies showed that clinical studies referred to the preclinical research mainly to justify their study or a future study (76%).

Discussion

Preclinical systematic reviews may have an influence on clinical research but their methodological quality frequently remains low. Therefore, systematic reviews of animal research should be critically appraised before translating them to a clinical context.     

Scapulothoracic muscle activity and recruitment timing in patients with shoulder impingement symptoms and glenohumeral instability

BackgroundVarious studies have investigated scapulothoracic muscle activity and recruitment patterns in relation to shoulder complaints in different populations, but a consensus review is lacking.Hypothesis/purposeTo systematically review the state of the art regarding scapulothoracic muscle activity and recruitment timing in subjects with shoulder pain compared to pain free controls.Study designSystematic review.MethodsThe search for relevant articles was performed in Pubmed and Web of Science, including Web of Knowledge, using key words related to shoulder pain, scapulothoracic muscle activity or recruitment timing. Articles were included till November 2012. Case-control studies concerning the scapulothoracic region and muscle recruitment using electromyography (EMG) were included. Articles regarding rotator cuff muscles or neck-shoulder pathologies or studies handling a treatment outcome, were excluded. The methodological quality of the articles was assessed using appropriate risk of bias criteria for case-control studies.ResultsA total of 12 articles were included in the systematic review, containing patients with Shoulder Impingement Syndrome (SIS) or glenohumeral instability. In patients with SIS 3 out of 6 articles showed increased upper trapezius muscle (UT) activity, 3 out of 5 studies showed decreased lower trapezius muscle (LT) activity and 3 out of 5 articles showed decreased serratus anterior muscle (SA) activity. Patients with glenohumeral instability showed contradictory results on scapulothoracic muscle activity patterns. In both SIS and glenohumeral instability patients, no consensus was found on muscle recruitment timing.ConclusionPatients with SIS and glenohumeral instability display numerous variations in scapulothoracic muscle activity compared to healthy controls. In the SIS-group, the LT and SA muscle activity is decreased. In addition, the UT muscle activity is increased among the SIS patients, whereas no clear change is seen among patients with glenohumeral instability. Although the scapulothoracic muscle activity changed, no consensus could be made regarding muscle recruitment timing.     

Use of lipid lowering drugs for primary prevention of coronary heart disease: meta-analysis of randomised trials

ObjectiveTo summarise the effect of primary prevention with lipid lowering drugs on coronary heart disease events, coronary heart disease mortality, and all cause mortality.DesignMeta-analysis.IdentificationSystematic search of the Medline database from January 1994 to June 1999 for English language studies examining drug treatment for lipid disorders (use of the MeSH terms “hyperlipidemia” and “anticholesteremic agents,” keyword searches for individual drug names, and a search strategy for identifying randomised trials to capture relevant articles); identification of older studies through systematic reviews and hand search of bibliographies.ResultsFour studies met eligibility criteria. Drug treatment reduced the odds of a coronary heart disease event by 30% (summary odds ratio 0.70, 95% confidence interval 0.62 to 0.79) but not the odds of all cause mortality (0.94, 0.81 to 1.09). When statin drugs were considered alone, no substantial differences in results were found.ConclusionsTreatment with lipid lowering drugs lasting five to seven years reduces coronary heart disease events but not all cause mortality in people with no known cardiovascular disease.     

Inhibitory effects of phytochemicals on NLRP3 inflammasome activation: A review

BackgroundThe NLRP3 inflammasome formation and following cytokine secretion is a crucial step in innate immune responses. Internal and external factors may trigger inflammasome activation and result in inflammatory cytokine secretion. Inflammasome formation and activity play critical roles in several disease pathologies such as cardiovascular, metabolic, renal, digestive, and CNS diseases. Underlying pathways are not yet clear, but phytochemicals as alternative therapies have been extensively used for suppression of inflammatory responses.PurposeIn this review, we aimed to summarize in vivo and in vitro effects on NLRP3 inflammasome activation of selected phytochemicals.MethodThree phytochemicals; Sulforaphane, Curcumin, and Resveratrol were selected, and studies were reviewed to clarify their intracellular signaling mechanism in NLRP3 inflammasome activity. PubMed and Scopus databases are used for the search. For sulforaphane, 8 articles, for curcumin, 25 articles, and for resveratrol, 41 articles were included in the review.ConclusionIn vitro and in vivo studies pointed out that the selected phytochemicals have inhibitory properties on NLRP3 inflammasome activity. However, neither the mechanism is clear, nor the study designs and doses are standardized.     

Use of Recommended Search Strategies in Systematic Reviews and the Impact of Librarian Involvement: A Cross-Sectional Survey of Recent Authors

BackgroundPrevious research looking at published systematic reviews has shown that their search strategies are often suboptimal and that librarian involvement, though recommended, is low. Confidence in the results, however, is limited due to poor reporting of search strategies the published articles.ObjectivesTo more accurately measure the use of recommended search methods in systematic reviews, the levels of librarian involvement, and whether librarian involvement predicts the use of recommended methods.MethodsA survey was sent to all authors of English-language systematic reviews indexed in the Database of Abstracts of Reviews of Effects (DARE) from January 2012 through January 2014. The survey asked about their use of search methods recommended by the Institute of Medicine, Cochrane Collaboration, and the Agency for Healthcare Research and Quality and if and how a librarian was involved in the systematic review. Rates of use of recommended methods and librarian involvement were summarized. The impact of librarian involvement on use of recommended methods was examined using a multivariate logistic regression.Results1560 authors completed the survey. Use of recommended search methods ranged widely from 98% for use of keywords to 9% for registration in PROSPERO and were generally higher than in previous studies. 51% of studies involved a librarian, but only 64% acknowledge their assistance. Librarian involvement was significantly associated with the use of 65% of recommended search methods after controlling for other potential predictors. Odds ratios ranged from 1.36 (95% CI 1.06 to 1.75) for including multiple languages to 3.07 (95% CI 2.06 to 4.58) for using controlled vocabulary.ConclusionsUse of recommended search strategies is higher than previously reported, but many methods are still under-utilized. Librarian involvement predicts the use of most methods, but their involvement is under-reported within the published article.     

The association between smokeless tobacco use and pancreatic adenocarcinoma: A systematic review

BackgroundSmokeless tobacco is a possible risk factor for developing pancreatic adenocarcinoma. This systematic review addressed the question: Is there an association between smokeless tobacco use and pancreatic adenocarcinoma diagnosis?MethodsFive electronic databases, grey literature, and citations of relevant articles were searched to identify studies. Six researchers double-reviewed records for inclusion in the review. The information extracted from these studies was selected using criteria outlined in the Newcastle–Ottawa Quality Assessment Scale for observational studies. A qualitative synthesis of included studies was performed.ResultsThe search of electronic databases resulted in a total of 1747 citations. Eleven studies met the inclusion criteria for this review, including three cohort studies, seven case control studies and one study that pooled data from multiple case-control studies. Studies were heterogeneous in their assessment of exposure intensity and ascertainment of outcomes. Quality of the studies varied. Existing investigations of the association of interest appear to exhibit several types of biases including selection bias, information bias and bias in the analysis.ConclusionThe association between smokeless tobacco use and pancreatic adenocarcinoma is inconclusive. More definitive conclusions regarding this relationship await the results of more methodologically rigorous epidemiologic studies.     

Circulating microparticles in cardiovascular disease: going on stage!

Context: Cardiovascular diseases (CVDs) are the leading cause of death worldwide. In spite of the fact that treatments are based on risk calculators which in turn are based on population characteristics, it is well known that these methods have definite levels of uncertainty. Recently, more precise diagnostic or predictive methods have been developed based on indicators of vascular and/or cardiac damage in order to supplement this risk evaluation.

Objective: In this review, we describe the main discoveries leading to the idea of using circulating microparticles as a promising and complementary tool in the evaluation of cardiovascular risk.

Methods: A Medline search for the terms cardiovascular diseases, microparticles, miRNAs, diagnosis, prognosis, biomarkers and microvesicles was performed.

Results: We found (i) nine articles, which were relevant to forming the idea of using microparticles as biomarkers in CVDs, and (ii) 15 and 12 experimental clinical studies which describe their potential in primary and secondary CVD prevention, respectively.

Conclusions: The levels of circulating microparticles have been associated with cardiovascular damage in asymptomatic patients as well as in patients who suffered a cardiovascular event, becoming promising diagnostics or prediction biomarkers in recent years.     

Antioxidant properties of drugs used in Type 2 diabetes management: could they contribute to,confound or conceal effects of antioxidant therapy?

Objectives: This is a narrative review, investigating the antioxidant properties of drugs used in the management of diabetes, and discusses whether these antioxidant effects contribute to, confound, or conceal the effects of antioxidant therapy.Methods: A systematic search for articles reporting trials, or observational studies on the antioxidant effect of drugs used in the treatment of diabetes in humans or animals was performed using Web of Science, PubMed, and Ovid. Data were extracted, including data on a number of subjects, type of treatment (and duration) received, and primary and secondary outcomes. The primary outcomes were reporting on changes in biomarkers of antioxidants concentrations and secondary outcomes were reporting on changes in biomarkers of oxidative stress. Results: Diabetes Mellitus is a disease characterized by increased oxidative stress. It is often accompanied by a spectrum of other metabolic disturbances, including elevated plasma lipids, elevated uric acid, hypertension, endothelial dysfunction, and central obesity. This review shows evidence that some of the drugs in diabetes management have both in vivo and in vitro antioxidant properties through mechanisms such as scavenging free radicals and upregulating antioxidant gene expression. Conclusion: Pharmaceutical agents used in the treatment of type 2 diabetes has been shown to exert an antioxidant effect..     

Parasympathetic Nervous System Dysfunction,as Identified by Pupil Light Reflex,and Its Possible Connection to Hearing Impairment

ContextAlthough the pupil light reflex has been widely used as a clinical diagnostic tool for autonomic nervous system dysfunction, there is no systematic review available to summarize the evidence that the pupil light reflex is a sensitive method to detect parasympathetic dysfunction. Meanwhile, the relationship between parasympathetic functioning and hearing impairment is relatively unknown.ObjectivesTo 1) review the evidence for the pupil light reflex being a sensitive method to evaluate parasympathetic dysfunction, 2) review the evidence relating hearing impairment and parasympathetic activity and 3) seek evidence of possible connections between hearing impairment and the pupil light reflex.MethodsLiterature searches were performed in five electronic databases. All selected articles were categorized into three sections: pupil light reflex and parasympathetic dysfunction, hearing impairment and parasympathetic activity, pupil light reflex and hearing impairment.ResultsThirty-eight articles were included in this review. Among them, 36 articles addressed the pupil light reflex and parasympathetic dysfunction. We summarized the information in these data according to different types of parasympathetic-related diseases. Most of the studies showed a difference on at least one pupil light reflex parameter between patients and healthy controls. Two articles discussed the relationship between hearing impairment and parasympathetic activity. Both studies reported a reduced parasympathetic activity in the hearing impaired groups. The searches identified no results for pupil light reflex and hearing impairment.

Discussion and Conclusions

As the first systematic review of the evidence, our findings suggest that the pupil light reflex is a sensitive tool to assess the presence of parasympathetic dysfunction. Maximum constriction velocity and relative constriction amplitude appear to be the most sensitive parameters. There are only two studies investigating the relationship between parasympathetic activity and hearing impairment, hence further research is needed. The pupil light reflex could be a candidate measurement tool to achieve this goal.     

Azadirachta indica A. Juss (neem) as a contraceptive: An evidence-based review on its pharmacological efficiency

BackgroundAzadirachta indica A. Juss. is an Indian medicinal plant with innumerable pharmacological properties. Studies have proven that the phytochemicals from neem possess remarkable contraceptive abilities with limited knowledge on its mechanism of action.PurposeThe present review aims to summarize the efficiency of A. indica treatment as a contraceptive.MethodsThe Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines were used. Published scientific articles on antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient activities of A. indica were collected from reputed Journals from 1980 to 2020 using electronic databases. Specific keywords search was completed to collect numerous articles with unique experiment design and significant results. This was followed by the selection of the requisite articles based on the criteria designed by the authors. Data extraction was based on the common research elements included in the articles.ResultsA total of 27 studies were considered for reviewing, which included key pharmacological investigations. In the beginning, authors evaluated a number of publications on the contraceptive properties of A. indica, in which it was revealed that most of the publications were made between 2005 and 2009. All the collected articles were categorised and reviewed as antifertility, antispermatogenic, antiovulation, hormone altering, contraceptive, and abortifacient. Authors also assessed studies based on the plant parts used for pharmacological evaluations including leaves, seeds, stem-bark, and flowers. The article was primarily divided into different sections based on the previous works of authors on phytochemistry and pharmacological review articles.ConclusionAlthough A. indica is not reported with the complete alleviation of reproductive system in both male and female animal models, studies have proven its efficacy as a contraceptive. Extracts and phytochemicals from neem neither reduced the libido nor retarded the growth of secondary sexual characters, thus indicating only a temporary and reversible contraceptive activity. However, there is a dearth for clinical studies to prove the efficacy of A. indica as a herbal contraceptive.     

Association of Plasma Parathyroid Hormone with Metabolic Syndrome and Risk for Cardiovascular Disease

ObjectiveTo review the current literature investigating the association of plasma parathyroid hormone (PTH) with the prevalence of metabolic syndrome and the risk for cardiovascular disease (CVD).MethodsWe conducted a search of PubMed and Medline database using the terms hyperparathyroidism, metabolic syndrome, hypertension, hyperlipidemia, hyper-glycemia, and CVD. We reviewed relevant studies from 2004 to 2012.ResultsThe current literature assessing the association of plasma PTH levels with metabolic syndrome and CVD is inconsistent; however, positive associations among hyperparathyroidism, metabolic syndrome, and CVD were found in a majority of the studies. The differences in the study populations may partly explain the mixed results.ConclusionIn the general population, a high serum PTH level predisposes patients to CVD mortality. Further research is needed to determine the role of PTH in the etiology of metabolic syndrome and CVD. (Endocr Pract. 2013;19:712-717)     

Adrenocorticotropic Hormone-Producing Pancreatic Neuroendocrine Neoplasms: A Systematic Review

ObjectiveAdrenocorticotropic hormone-producing pancreatic neuroendocrine neoplasm (ACTHoma) is an exceedingly rare type of pancreatic neuroendocrine neoplasm (pNEN) that often causes ectopic adrenocorticotropic hormone syndrome. These neoplasms have been found to be very aggressive and challenging to treat. The current systematic review aimed to analyze the clinical features, immunohistochemical characteristics, diagnosis, therapy, and prognosis of ACTHoma.MethodsA systematic review of the English- and Chinese-language literature was performed. PubMed, EMBASE, and Wanfang databases were searched to identify articles about ACTHoma in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines.ResultsA total of 210 studies encompassing 336 patients diagnosed with ACTHoma were selected for the systematic review, including 16 Chinese patients.ConclusionACTHoma was more common in women (66.4%), and the mean age was 44.7 years. Tumors were generally large, and the mean tumor size was 4.43 cm. The incidence of clinical manifestations was: hypokalemia, 69.3%; diabetes, 63.2%; weakness, 60.1%, hypertension, 56.4%; moon face 41.1%; and edema, 37.4%. These tumors are more commonly found in the tail of pancreas, and the most frequent site of metastasis was the liver. The pNENs or other functioning pNENs could evolve into ACTHoma. ACTHoma is a very rare disease, and the mean follow-up time was 28.3 months.