systematic review

Background: With the outbreak of Coronavirus disease 2019 (COVID-19), many studies’ attention to this world’s complexity increased dramatically. Different views on sports and physical activities have been presented, which have addressed the advantages and disadvantages of sports activities in this period differently. The purpose of this review was to investigate the physiological and psychological effects of physical activity during the COVID-19 pandemic. Methods: Using PubMed, Science Direct, Medline, and Web of Science electronic databases, this review summarizes the current knowledge of direct and indirect effects of physical activity during the COVID-19 pandemic, evaluating the advantages and drawbacks of specific exercise physiology conditions. All types of studies were assessed, including systematic reviews, case-studies, and clinical guidelines. The literature search identified 40 articles that discussed COVID-19, immune system, the relation between immune system and exercise or diet, and psychological impacts of physical activity. Results: Forty articles review showed that the immune system depends on the type, frequency, intensity, and duration of the exercise. Intense or prolonged exercise with short recovery periods can progressively weaken the immune system and increase the risk of COVID-19. One of the acute responses after moderate-intensity training is improved immune function and a decrease in inflammatory cytokines. Paying attention to dietary intakes of micro-and macronutrients in conjunction with exercise can strengthen the condition to fight against coronavirus. Exercise can also affect the psychological dimensions of the COVID-19 pandemic, including depression, anxiety, and stress, which improve community mental health during the quarantine. Conclusion: Setting appropriate physical activity based on individuals’ properties and proper diet plan may enhance the physiological and psychological body’s condition to fight against coronavirus.

Introduction: Acupuncture is a practice that has been used to treat multiple medical conditions for thousands of years and is one of the most popular alternative treatments applied in Western medical practice. Acupuncture is a modality that has significant potential for further integration into the treatment of sports medicine conditions. Methodology: The search strategy in this review included electronic databases-MEDLINE, Cochrane Library, PubMed, Web of Science, and Science Direct. Randomized controlled trials and systematic reviews were preferred for article inclusion, but other study types were included when the number or quality of evidence was limited. Results: Back pain, neck pain, shoulder pain, and knee pain related to OA tend to respond well to acupuncture treatment. There is evidence to support the use of acupuncture for the short-term treatment of plantar fasciitis, although long-term efficacy data is lacking. Acupuncture may be a useful treatment modality for epicondylitis and Achilles tendinopathy, but the current data is limited. While acupuncture may improve athletic performance and prevent Delayed-Onset Muscle Soreness (DOMS) symptoms, there is little current evidence to support this use. Conclusion: Further studies are needed to assess the usefulness of acupuncture in sports medicine. However, there is good evidence for the current use of acupuncture in treatment of multiple pain conditions.

Background: Early diagnosis and improved facilities are necessary for determining the optimal timing of surgery and other interventions in children with congenital heart diseases in Nigeria. This is because late presentation, late diagnosis and delayed surgery can lead to mortality and affect the quality of life among these children. Objectives: This review article is aimed at enumerating the timing of cardiac surgeries and other interventions and to seek if there is any factor associated with the timing of cardiac surgery. Methods: A search on PubMed database, World Health Organization libraries, Google scholar, TRIP database, and reference lists of selected articles on timing of cardiac surgery in children was done. The Cochrane Database of Systematic Reviews was also searched. We noted few data from African setting. Key words such as timing of cardiac surgery; children, congenital heart defect were used. Conclusion: Appropriate timing for cardiac surgery in children with congenital heart disease is very important as late surgical intervention could result in several morbidities and mortality.

Background: Hypertrophic cardiomyopathy (HCM) patients have a predisposition for malignant VT/VF and consequently, sudden cardiac death (SCD). In single center studies, late gadolinium enhancement (LGE) defined fibrosis has been linked to VT/VF. However, despite innumerable investigations, SCD has not been definitely attributable to LGE. Explanations for these are believed to be related to insufficient statistical power. Methods: We performed an electronic search of MEDLINE, PubMed: and CMR abstracts for original data published or presented between Jan 2001 to Mar 2011. Key search terms: HCM, LV fibrosis, SCD and LGE. Studies were screened for eligibility based on inclusion criteria: referral for CMR exam with LGE for HCM; and follow-up for incidence of VT/VF and SCD. Categorical variables were evaluated between patient groups via Chi-square test. Results: A total of 64 studies were initially identified. Of these, 4 (6.3%) were identified and included (n = 1063 patients). Three prospective and one retrospective study were included. LGE was detected in 59.6% of patients. As expected, the presence of myocardial fibrosis was associated with VT/VF (x2 = 6.5, p < 0.05; OR 9.0, (95% CI 1.2 to 68.7). Moreover, myocardial fibrosis strongly predicted SCD (x2 = 6.6, p < 0.05; OR 3.3 (95% CI 1.2 to 9.7). Conclusion: Despite single center CMR studies, LGE has consistently predicted VT/VF while prediction of SCD has remained paradoxically unlinked. Although the lack of studies meeting our criteria limited our ability to perform a comprehensive meta-analysis, we have been able to demonstrate for the first time that LGE-defined fibrosis is a predictor of SCD in patients with HCM0.

Cissus quadrangularis a succulent vine belongs to Vitaceae family is widely distributed throughout tropical and subtropical regions of the world and used frequently to various disorders. The plant has been reported to contain flavonoids, triterpenoids, phytosterols, glycosides and rich source of calcium. This study aims to bring a systematic review of C. quadrangularis in various pharmacological mechanisms. Evidence from the previous studies suggested the efficacy of C. quadrangularis with antimicrobial, anti-diabetic, anti-inflammatory, anti-obesity, anti-oxidant, bone turnover, cardiovascular and hepatoprotective activities. In conclusion, Cissus quadrangularis appears worthy of pharmacological investigations for new drug formulations.

Drug-induced Hepatotoxicity and biologic drugs have historically been challenging in IBD. We aim to study the prevalence of hepatotoxicity in adult patients using biologic medications.

Introduction: Necrotizing Fasciitis (NF) is a rapidly progressing, severe suppurative infection of the superficial fascia and the sorrounding tissues that may lead to necrosis, septic shock and death if left untreated. Facial NF is rarely seen and symptoms may be non-specific at the onset and depend on the origin site and the stage of the disease, making it difficult for diagnosis. Materials and Methods: A systematic review was done following the PRISMA guidance. PubMed database was searched for case reports published between January 2007 and March 2017. Full text articles were obtained and assesed for relevance. Data extraction was performed as an iterative process. Results: A total of 24 articles, describing 29 adult patients with facial NF were included. Facial NF was more common in males. Skin trauma was the most frequent mechanism of lesion and diabetes mellitus was the most common associated systemic disorder. Periorbital area was the most affected area. In order of appereance, swelling and pain were the most common initial clinical manifestations. Group A Streptococcus was the most frequent microorganism isolated. Advanced airway management was needed in more than 50% of the cases and surgical management was done in 90% of the cases. Conclusions: Practitioners should be aware of its existance, epidemiology, etiology, risk factors and initial clinical manifestations to develop a high index of suspicion, to order studies that may discard or confirm the diagnosis, and to offer prompt treatment to preserve patient’s life and reduce the disfigurement and disability that it may cause.

Background: Hypertension is the leading cause of cardiovascular diseases and premature deaths. Hypertension plays a striking role in mortality and morbidity in case of Coronavirus Disease 2019 (COVID-19) infection; however, numerous studies have reported contradictory findings. Objective: To assess the relationship of hypertensive disease and mortality of COVID-19 infection and to assess the sex and age differentials on the association. Methods: We have conducted a systematic review of published literatures that identified the relationship between hypertension and mortality of COVID-19 infections. Nineteen articles were selected following structured inclusion and exclusion criteria for systematic review and analyses. A total of 21,684 hospital admitted COVID-19 patients were included in this review and meta-analysis from 19 studies. The studies covered the six months of the pandemic from December 2019 to May 2020. Results: In the pooled analysis, the median age of patients was 58 years, and the proportion of male patients was 58.8%. In contrast, we estimated 33.26% of hypertensive and 19.16% of diabetes mellitus patients in the studies. Hypertension was found to be associated with COVID-19 mortality (“Risk ratio (RR) = 1.45, [95% confidence interval (CI): 1.35 - 1.55]; I2 = 77.1%, p - value < 0.001”). The association in the meta-regression was affected by sex (p - value = 0.050). The association was found to be stronger in the studies with males ≥ 55% and age ≥ 55 years (“RR = 1.65, [95% CI: 1.52 - 1.78]; I2 = 77.1%, p - value < 0.001”) compared to male < 55% or age < 55 years (“RR = 1.11, [95% CI: 0.94 - 1.28]; I2 = 72.2%, p - value < 0.001”). Conclusion: Hypertension was significantly strong associated with COVID-19 mortality which may account for the contradiction in the many studies. The association between hypertension and mortality was affected by sex and there were significantly higher fatalities among older male patients. 

Background: Hyperuricosuria, persistently low urinary pH, and low urinary volume are the main risk factors of uric acid nephrolithiasis. Epidemiologic studies suggest that high water intake is protective against the occurrence of symptomatic kidney stone events of all types. The objective of this systematic review and meta-analysis were to evaluate the effectiveness of increased water intake to prevent symptomatic uric acid kidney stone events. Methods: Seventeen studies were identified for the meta-analysis. Analysis of Q and I2% statistics revealed that a high heterogeneity in 16 studies, thus, random effects model was used. Protective associations were identified for high water intake individuals (SMD=0.52 L; 95% CI: 0.19, 0.84; p=0.002); a significantly decreased relative super saturation of uric acid versus controls (SMD=-1.15; 95% CI: -2.00, -0.30; p=0.008). Risk factors including urinary uric acid excretion and pH were not significantly related to high water intake (SMD=7.32mg/d, 95% CI: -52.27, 66.91; p=0.81), (SMD=0.14; 95% CI: -0.02, 0.31; p=0.09), respectively. Further subgroup analyses revealed that urinary uric acid excretion was significantly decreased in healthy individuals (SMD=-36.23 mg/d, 95% CI: -65.14, -7.31; p=0.001) compared to stone formers (SMD=27.41 mg/d, 95% CI: -33.18, 88.01; p=0.38); urinary uric acid excretion was significantly decreased in routine water intake groups (SMD=-61.49 mg/d, 95% CI: -120.74, 12.24; p=0.04) compared to mineral water intake groups (SMD=44.50 mg/d, 95% CI: -18.30, 107.29; p=0.16); urinary pH was significantly higher in mineral water groups (SMD=0.13, 95% CI: 0.01, 0.46; p=0.04) compared to regular water groups (SMD=-0.00, 95% CI: -0.13, 0.13; p=0.98). Results: A total of 129 patients had 150 internal jugular catheter insertions. The mean age was 51.4±15.2 years with male to female ratio of 1.5:1. All the patients had chronic kidney disease; about 80% had tunneled IJC and 96.9% of the catheters were inserted in the right internal jugular vein. Immediate complications were recorded in 10% and late complications in 34.9% of the procedures. The immediate complications were kinking of guide wire (2%), arterial puncture (1.3%) and difficulty in locating the internal jugular vein (1.3%) or tunneling (1.3%). The late complications were infection (12.8%), poor blood flow (9.2%), bleeding (5.5%) and spontaneous removal of the catheter (5.5%). There was no statistical significant difference in both immediate and late complication with age and sex. Conclusion: This meta-analysis identified evidence that urinary uric acid excretion, volume, pH and relative supersaturation of uric acid can be altered with high water intake intervention, reducing the risk of uric acid kidney stones.

This non-systematic review outlines the current knowledge concerning provenance, chemical composition and properties of apple cider vinegar, its general health effects, as well as the currently available knowledge concerning its action on fat storage, physiological mechanisms of its effects, as well as its safety and recommended dosage for treatment of obesity. 

Background: Herbal essential oil contains pharmacological benefits for intervention treatment of various diseases. Studies have demonstrated its antimicrobial, antioxidant, and anti-inflammatory effect involving in vitro cell culture and preclinical animal models. It has been also traditionally used to reduce anxiety and hypertension in human. However, scientific studies elucidating its mechanism of action and pharmacological targets, as well as its effectiveness and safety as phytotherapeutic compounds are still progressing. Recent studies showed its promising effect in depression-cardiovascular disease intervention. However, comprehensive evaluations to enlighten latest advancement and potential of herbal essential oil are still lacking. Objective: In this systematic review, the depression-cardiovascular effects of herbal essential oil on lipid profile, biochemical and physiological parameters (e.g haemodynamic) are presented. The route of delivery and mechanism of action as well as main bioactive compounds present in respective essential oil are discussed. Methods: Article searches are made using NCBI PubMed, PubMed Health, SCOPUS, Wiley Online, tandfonline, ScienceDirect and Espacenet for relevant studies and intellectual properties related to essential oil, depression and cardiovascular disease. Results: In experimentation involving in vitro, in vivo and clinical trials, herbal essential oil showed its effectiveness in reducing coronary artery disease (narrowing of the arteries), heart attack, abnormal heart rhythms, or arrhythmias, heart failure, heart valve disease, congenital heart disease, heart muscle disease (cardiomyopathy), pericardial disease, aorta disease, Marfan syndrome and vascular (blood vessel) disease. Conclusion: This review gives a valuable insight on the potential of essential oil in the intervention of depression associated with cardiovascular diseases. Studies showed that herbal essential oil could act as vasodepressor, calcium channel blocker, antihyperlipidemia, anticoagulant, antiatherogenesis and antithrombotic. It can be proposed as an interventional therapy for depression-cardiovascular disease to reduce doses and long-term side-effect of current pharmacological approach.

More than 200 countries have been devastated by the SARS-CoV-2 pandemic. The health workers exposed to SARS patients have been confirmed to be infected with coronavirus (SARS-CoV-2), regardless of the degree of their exposure. The increasing complexity of virus existence and heterogeneity has cast doubt on disinfectants as a viable choice. Hence, the present systematic review aims to achieve the comparative analysis of established disinfectants against enveloped and non-enveloped viruses including SARS-CoV and MERS-CoV. Three databases (Pubmed, Google scholar, and Medline) were searched to frame the systematic review. Our comparative analyses with 34 studies have found that 85% ethanol-based hand sanitizers and 7.5% Povidine Iodine based soaps/surgical scrub could be used to deter the SARS-CoV-2 virus as preferred hand sanitizers. For surface eradication, 0.5% sodium hypochlorite or a mixture of glutaraldehyde, Quaternary Ammonium Compounds (QAC), and isopropanol could have more efficacies as compared to hydrogen peroxide, phenol, and QAC alone. Moreover, the accelerated hydrogen peroxide as an active ingredient in the automatic quick surface disinfectant (tunnel system), maybe a positive indication for quick whole-body sanitation. Additionally, the alternative method for avoiding the rapidly increasing chain of infection with SARS and restarting regular life has been exclusively discussed.

Aim: With the continuing trend in the incidence of diabetic ulcer, the current researches on wound care and healing will bring best and effective practices on wound care and healing among patients suffering from diabetes mellitus. Methods: This study utilized a systematic review of literatures in light of wound care through Pub Med database with the key words “Diabetes Mellitus,” “wound practices,” “wound healing,” and “systematic review.” The searched literatures were of case reports, interventional studies, and review papers whose main texts were in English. Results: There were 7,988 published articles yielded from the keywords used and 16 were included in this study. The practiced management and techniques in these literatures focused on comfortable and cost efficient means of wound care and healing with the involvement of group participation than individual plan of care. Conclusions: There are meager evidences of feasible wound and healing options that needs further studies in resolving wound issues among patients with Diabetes Mellitus. This systematic review establishes the insufficiency of high level of evidence based studies on wound healing in DM patients and brings a track for continuity of rigid studies concerning this topic.

Background: NSU is generally caused by right cerebral hemisphere lesions with a preeminent localization on the frontoparietal lobe. Aim: To assess the correlation between the typology and the brain lesion site and the consensual consent modality of body image modification after an integrated rehabilitative and neuropsychological treatment. Setting: A rehabilitation institute for the treatment of neurological gait disorders and neuropsichological failures. methods: Patients recruited were divided according to the brain lesion site into 3 groups (IG = ischemic group = 5 patients; HG = hemorrhagic group = 4 patients; IG + HG = ischemic + hemorrhagic group = 3 patients) based on CT brain performed in the post-acute phase. At time T0, the patients recruited underwent a systematic review of their current neuroradiological profile (location delineation and type of brain injury) compared with a consensual framing of the neuromotor and neuropsychological profile acquired at the time of taking charge in the ward. At time T1 and after the drafting and implementation of the rehabilitation treatment plan foreseen in the study (1 to 4 months after T0), the patients in our sample underwent a re-evaluation of their neuromotor and neuropsychological profile with controls of the same outcome parameters considered at time T0. Results: A parametrically but not statistically significant modification of the results obtained was observed by measuring the MI ULl, MI LLl and TCT scales in the group with hemorrhagic brain injury; the analysis of variance did not show any statistical significance in the relationship between the type of stroke (ischemic, hemorrhagic or both) and the motor impairment passing from time T0 to time T1. The analysis of variance did not reveal a statistically or parametrically significant relationship between the type (ischemic, hemorrhagic and ischemic + hemorrhagic) of cerebral stroke and the variations of the neuropsychological profile. The T-Student test showed statistically significant changes in the importance of the lesion site in defining the degree of motor disability. In particular, we observed, about the presence of frontal lobe lesions, a statistically significant variation passing from the T0 time to the T1 time for the following motor scales in 9 of 12 recruited patients: MI LLl (26.4 vs. 62, with p < 0.05), TCT (43.6 vs. 80.6, with p < 0.01 for equal variance assumed and p < 0.05 for equal variance not assumed), FAC (0.8 vs. 2.3 with p < 0,01 for equal variance assumed and p < 0.05 for equal variance not assumed). Conclusion: We have confirmed the importance of the anatomical-dysfunctional correlation as a key concept from which to start in any neurorehabilitative treatment approach. Our work has highlighted the basic role of the right frontal lobe in the programming and execution of the gesture and its kinesthetic control as regards the left lower limb and the trunk.

Background: The argument on whether extracorporeal shock-wave therapy (ESWT) is beneficial in short- term intervention in adults with plantar fasciitis. It is important and necessary to conduct a meta-analysis to make a comparatively more reliable and overall assessment of the outcomes of ESWT in the less than 6 months. Methods: We conducted a systematic review and meta-analysis of randomized control trials from MEDLINE, EMBASE and CINAHL databases from 2000 to 2020. Randomized trials that evaluated extracorporeal shock wave therapy used to treat plantar heel pain were included. Trials comparing an extra corporeal shock wave therapy with control/placebo were considered for inclusion in the review. We independently applied the inclusion and exclusion criteria to each identified randomized controlled trial, extracted data and assessed the methodological quality of each trial. Results: Four studies involving 645 patients were included. 3 RCTs (n = 605) permitted a pooled estimate of effectiveness based on overall success rate and composite score of visual analogue scales for pain at follow-up 1 (12 weeks). The pooled data showed no significant heterogeneity at the three-month follow-up (p - value of chi-square = 0.61, p = 0.74 and I2 = 0%). The shock wave group had a better success rate than the control group at the three-month follow-up (OR = 2.26, 95% CI = 1.62-3.15, p - < 0.00001). For reduction of pain the pooled data showed no significant heterogeneity (p - value of chi-Square 0.28 and I2 22%). There were significant differences between the ESWT and control groups for all follow-up visits (random-effect model, three trials, MD = 15.14, 95% CI = 13.86 to 16.42, < 0.00001 at three-month). Conclusion: A meta-analysis of data from three randomized-controlled trials that included a total of 605 patients was statistically significant in favor of extracorporeal shock wave therapy at follow-up 1(12 weeks).

Background: Thrombotic microangiopathy (TMA) is a rare and life-threatening complication of prostate carcinoma. Whether plasma exchange has a role in treatment remains a subject of debate. Here we present a case followed by a systematic review of the literature on this subject. Case report: We describe a 69-year old patient presenting with TMA, which was associated with an underlying metastatic prostate carcinoma. We conducted a search of similar cases in literature. Results: Our patient was treated and responded well on plasma exchange. Systematic review of the literature showed 17 additional cases of TMA associated with prostate carcinoma of which eleven were treated with plasma exchange with mostly good response. Conclusion: Based on current data we cannot exclude a potential role for plasma exchange in prostate cancer associated TMA.

Marijuana is considered illicit in much of the world, and is classified as a drug for recreational use, in recent decades the medicinal use of Cannabis sativa L. has grown and diversified, being considered the only therapeutic alternative in the control of serious and incurable diseases such as syndrome of Dravet. The world panorama has shown a more liberal position, since in several countries such as the United States of America, Holland, Australia, Italy, and more recently in Canada, the use of medications, or even the recreational use of this plant, have been regulated. In this context, the investigation of the modifying effects on physical activity of empirically used cannabinoids is fundamental nowadays, mainly due to the regulatory recognition of Cannabis sativa L. as a medicinal plant in a large part of the world. Therefore, the objective of this review was to verify the evidence related to the effect of cannabis on physical performance and to identify and highlight the challenges in the interpretation of information regarding the performance of practitioners of physical activity, as well as athletes, presenting new trends in this area of research to be addressed. To carry out the systematic review, a bibliographic survey of case reports was obtained through Pubmed, Science Direct and Google Academic databases. The following keywords were used to perform the research: cannabis, performance, pain, competition. The following filters were used as inclusion criteria a languages used english; species: humans; types of articles: original articles and reviews and period of publication of articles: 1981 to 2021.

The commonest etiology of acute kidney injury (AKI) is Sepsis that results in an escalation of morbidity and mortality in the hospital intensive care units. Existentially, the therapy of septic AKI rather than being definitive or curative is just supportive, without tackling the pathophysiology. Usually, Sepsis gets correlated with systemic inflammation, along with the escalated generation of Reactive oxygen species (ROS), in particular superoxide. Simultaneously liberation of nitric oxide (NO) subsequently reacts with the superoxide, thus, resulting in the generation of reactive nitrogen species (RNS), that is mostly peroxynitrite. This sepsis stimulated generation of ROS in addition to RNS might cause a reduction in the bioavailability of NO that modulates microcirculation aberrations, localized tissue hypoxia as well as mitochondrial impairment, thus starting a vicious cycle of cellular damage which results in AKI. Here we conducted a systematic review utilizing search engine PubMed, Google scholar; Web of science; Embase; Cochrane review library utilizing the MeSH terms like septic AKI; ROS; inducible nitric oxide synthase (iNOS); nicotinamide adenine nucleotide phosphate(NADPH)oxidase complex; Oxidative stress; Renal medullary hypoxia; Hypoxia inducible factor1; hypoxia responsive enhancer A; mitochondrial impairment; Intrarenal oxygenation; urinary oxygenation; erythropoietin gene; RRT; NAC; Vitamin C from 1950 to 2021 till date. We found a total of 6500 articles out of which we selected 110 articles for this review. No meta-analysis was done. Thus here we detail the different sources of ROS, at the tie of sepsis, besides their pathophysiological crosstalk with the immune system, microcirculation as well as mitochondria that can result in the generation of AKI. Furthermore, we detail the therapeutic utility of N-acetylcysteine (NAC), besides the reasons for its success in ovine as well as porcine models of AKI. Moreover, we discuss preclinical along with clinical for evaluation of Vitamin C’s antioxidant effects as well as pleiotropic effects as a stress hormone that might aid in abrogation of septic AKI.

Chronic Kidney Disease (CKD) by definition is a disease characterized by irreversible elimination of renal function, which keeps propagating as corroborated by an estimated glomerular filtration rate (eGFR) of < 60 ml/min/1.73m2, the constant existence of presentation which pointed to Kidney injury (proteinuria, active sediments of urine, histological injury, structural aberrations or prior history with regards to Kidney transplantation) or both that are persistent for greaterthan 3 mths [1].

Steady-state VEPs, have been used to estimate visual acuity since the 1970s and allow responses to a range of stimulus sizes to be collected rapidly- with particular utility in infants. However, the assessment of children with cortical visual impairment is a bigger challenge that lead to the development of the Step VEP. Its initial evaluation revealed that accuracy and precision were poorer for pediatric patients than for optically degraded normal adults and that it was not necessarily successful in every child. Statistical models generated the equations: VAO = 0.56 VAStep (r2 = 0.75, F = 60.93, p = 0.000) and VAPL = 0.45 VAStep (r2 = 0.82, F = 156.85, p = 0.000), supported by a recent a systematic review of VA comparisons showing that recognition VA (optotypes) agrees more closely than discrimination VA (PL) with VEP VA. In combination, Step VEPS and subjective tests allowed complete assessment in 96% of patients, with incomplete Step VEPS much more likely to be partially successful than not, and more likely to be partially successful than incomplete subjective tests. This supports the rationale that Step VEPs maintain attention by limiting the time spent stimulating away from an individual’s threshold of spatial resolution. For the small number of patients in whom VA cannot be estimated, alternative stimuli and methods of presentation are proposed.