Phytochemical Compounds and Protection from Cardiovascular Diseasesa. A State of the Art

Cardiovascular diseases represent a worldwide relevant socioeconomical problem. Cardiovascular disease prevention relies also on lifestyle changes, including dietary habits. The cardioprotective effects of several foods and dietary supplements in both animal models and in humans have been explored. It was found that beneficial effects are mainly dependent on antioxidant and anti-inflammatory properties, also involving modulation of mitochondrial function. Resveratrol is one of the most studied phytochemical compounds and it is provided with several benefits in cardiovascular diseases as well as in other pathological conditions (such as cancer). Other relevant compounds are Brassica oleracea, curcumin, and berberine, and they all exert beneficial effects in several diseases. In the attempt to provide a comprehensive reference tool for both researchers and clinicians, we summarized in the present paper the existing literature on both preclinical and clinical cardioprotective effects of each mentioned phytochemical. We structured the discussion of each compound by analyzing, first, its cellular molecular targets of action, subsequently focusing on results from applications in both ex vivo and in vivo models, finally discussing the relevance of the compound in the context of human diseases

THE SOCIAL AUDIT AND SOCIAL ACCOUNTABILITY AMBIGUITIES IN THE CONTEXT OF THE PARTICIPATORY BUDGETING ADOPTION

An interesting initiative introduced in the public sector in recent years is participatory budgeting (PB), which has gained popularity, particularly with the advent of the New Public Governance (Touchton et al., 2023; Wampler & Touchton, 2019). PB aims to develop democratic strategies that allow communities to exercise popular control over decision-making processes (Mattei et al., 2022). While the preparatory side of PB has been extensively investigated in the literature, the user side remains largely unknown (Bartocci et al., 2022). In this light, it is possible to hypothesize that involving citizens in the evaluation and monitoring phases could improve the alignment between policy-making and citizens‘ expectations (Mattei et al., 2022). From this perspective, it becomes interesting to focus on social audit, which is a crucial process for an organization‘s social accountability. It is characterized by openness, transparency, and accountability, involving all stakeholders (Sathiabama, 2018). It serves as a managerial control mechanism that measures intangible and qualitative issues (Cotton, 2000). The purpose of a social audit is to enable organizations to evaluate and demonstrate their social, ethical, economic, and environmental benefits, as well as aspects related to health, working conditions, human rights, ethical rights, social protection, and transparency (Cotton, 2000; Humphrey & Owen, 2000; Sathiabama, 2018). It provides an assessment of an organization‘s performance and non-financial objectives by showcasing the achievement of its social goals and monitoring stakeholders‘ opinions (Sathiabama, 2018). However, the literature on this topic is still underdeveloped, and uncertainties persist, particularly regarding the terms used (e.g., ―social audit‖, ―social accountability‖, ―voice and accountability‖, or ―social control‖ used as synonyms) and the implied concepts (e.g., social auditing sometimes seen as equivalent to social accountability, while other times seen as a tool for it) (Baltazar & Sepúlveda, 2015). Therefore, considering the significance of participatory budgeting and the ambiguities surrounding social audit (or accountability), the aim is to understand how previous studies have analyzed the relationships between ―social audit‖ or ―social accountability‖ and ―participatory budgeting‖ to clarify the existing relations between these terms, given the aforementioned ambiguities about social audit and social accountability. To achieve this aim, a structured review of the literature (Massaro et al., 2016) has been carried out. In light of the purpose of the study, the keywords ‗participatory budget*‘ and ‗social audit*‘ and ‗social account*‘ were chosen in the string TITLE-ABS-KEY (―participatory budget*‖ and (―social audit*‖ or ―social account*‖)). This string was searched on Scopus because it is the most widely used and most available database for multidisciplinary scientific literature (De Moya-Anegón et al., 2007). The search was done in title, abstract and keywords because these are considered the sections‘ articles that typically contain keywords (Dal Mas et al., 2019; Natalicchio et al., 2017; Paoloni et al., 2020). The available papers were twelve. Then, the search was restricted to papers written in English to avoid translation problems (Mauro et al., 2017). Finally, two contributions were removed: a book that was a duplicate and a paper that was out of topic. Therefore, the eligible sample includes ten contributions. This analysis highlights the path of social auditing and its implications in the participatory process, like PB. The ten manuscripts have different natures; in detail: five are articles, and five are book chapters. Longitudinal analysis shows that the first publication dates to 2010 and that, thereafter, scientific production on this topic is very patchy. In fact, some years (2017, 2018 and 2021) present a couple of publications per year. In other years (2011, 2013, 2014, 2015, 2016 and 2020), no articles are published. Looking at the geographical content considered by the authors of the eligible manuscripts, following the categorisation used by (Broadbent & Guthrie, 2008; Paoloni et al., 2020), it is possible to highlight that two documents have not considered a particular case because are literature review or conceptual paper. Then, four documents analysed the Asia context, followed by three manuscripts from Central and South America and only one document from Africa and the Middle East. The eligible studies are carried out with various methodologies; in detail: 7 used qualitative methods, only one author used a quantitative method, one used a conceptual, and one used a literature review. Finally, analysing the papers‘ content, it is possible to highlight how, over time, the social audit has become a means used not only by private companies to reconcile economic and social objectives (Evans et al., 1998) but also in the public sector, as the participatory budgeting, a participatory governance tool, even if they do it differently. Based on the literature review, social audit and participatory budgeting are considered tools within the broader concept of social accountability. Some authors (Chowdhury & Panday, 2018) see them as interconnected, while others view participatory budgeting as a means to enhance social accountability without explicitly mentioning social audit (Touchton et al., 2023). Future research could try to clarify these grey areas that have been highlighted. Further evidence emerges regarding the need to produce contextualised studies in Europe as well as a lack of quantitative studies analysing the above-mentioned phenomena. This study aims to emphasize the significance of social auditing, despite the persisting ambiguities surrounding the use of terms like social audit or social accountability in the context of PB. Additionally, it contributes by analyzing the present state of social auditing and social accountability in PB, highlighting the public sector reforms implemented during the analyzed period

Remarkable diversity of intron-1 of the para voltage-gated sodium channel gene in an Anopheles gambiae/Anopheles coluzzii hybrid zone.

BACKGROUND: Genomic differentiation between Anopheles gambiae and Anopheles coluzzii--the major malaria vectors in sub-Saharan Africa--is localized into large "islands" toward the centromeres of chromosome-X and the two autosomes. Linkage disequilibrium between these genomic islands was first detected between species-specific polymorphisms within ribosomal DNA genes (IGS-rDNA) on the X-chromosome and a single variant at position 702 of intron 1 (Int-1702) of the para Voltage-Gated Sodium Channel (VGSC) gene on chromosome arm 2 L. Intron-1 sequence data from West and Central Africa revealed two clearly distinct and species-specific haplogroups, each characterized by very low polymorphism, which has been attributed to a selective sweep. The aim of this study was to analyse Int-1 sequence diversity in A. gambiae and A. coluzzii populations from the Far-West of their range, in order to assess whether this selective-sweep signature could persist in a zone of high interspecific hybridization. METHODS: A 531 bp region of VGSC Int-1 was sequenced in 21 A. coluzzii, 31 A. gambiae, and 12 hybrids from The Gambia and Guinea Bissau, located within the Far-West geographical region, and in 53 A. gambiae s.l. samples from the rest of the range. RESULTS: Far-West samples exhibit dramatic Int-1 polymorphism, far higher within each country than observed throughout the rest of the species range. Moreover, patterning of haplotypes within A. coluzzii confirms previous evidence of a macro-geographic subdivision into a West and a Central African genetic cluster, and reveals a possible genetic distinction of A. coluzzii populations from the Far-West. CONCLUSIONS: The results suggest a relaxation of selective pressures acting across the VGSC gene region in the hybrid zone. Genetic differentiation in the Far-West could be attributable to a founder effect within A. coluzzii, with subsequent extensive gene flow with secondarily-colonizing A. gambiae, potentially yielding a novel insight on the dynamic processes impacting genetic divergence of these key malaria vectors

Colorectal Cancer Stage at Diagnosis Before vs During the COVID-19 Pandemic in Italy

IMPORTANCE Delays in screening programs and the reluctance of patients to seek medical attention because of the outbreak of SARS-CoV-2 could be associated with the risk of more advanced colorectal cancers at diagnosis. OBJECTIVE To evaluate whether the SARS-CoV-2 pandemic was associated with more advanced oncologic stage and change in clinical presentation for patients with colorectal cancer. DESIGN, SETTING, AND PARTICIPANTS This retrospective, multicenter cohort study included all 17 938 adult patients who underwent surgery for colorectal cancer from March 1, 2020, to December 31, 2021 (pandemic period), and from January 1, 2018, to February 29, 2020 (prepandemic period), in 81 participating centers in Italy, including tertiary centers and community hospitals. Follow-up was 30 days from surgery. EXPOSURES Any type of surgical procedure for colorectal cancer, including explorative surgery, palliative procedures, and atypical or segmental resections. MAIN OUTCOMES AND MEASURES The primary outcome was advanced stage of colorectal cancer at diagnosis. Secondary outcomes were distant metastasis, T4 stage, aggressive biology (defined as cancer with at least 1 of the following characteristics: signet ring cells, mucinous tumor, budding, lymphovascular invasion, perineural invasion, and lymphangitis), stenotic lesion, emergency surgery, and palliative surgery. The independent association between the pandemic period and the outcomes was assessed using multivariate random-effects logistic regression, with hospital as the cluster variable. RESULTS A total of 17 938 patients (10 007 men [55.8%]; mean [SD] age, 70.6 [12.2] years) underwent surgery for colorectal cancer: 7796 (43.5%) during the pandemic period and 10 142 (56.5%) during the prepandemic period. Logistic regression indicated that the pandemic period was significantly associated with an increased rate of advanced-stage colorectal cancer (odds ratio [OR], 1.07; 95%CI, 1.01-1.13; P = .03), aggressive biology (OR, 1.32; 95%CI, 1.15-1.53; P < .001), and stenotic lesions (OR, 1.15; 95%CI, 1.01-1.31; P = .03). CONCLUSIONS AND RELEVANCE This cohort study suggests a significant association between the SARS-CoV-2 pandemic and the risk of a more advanced oncologic stage at diagnosis among patients undergoing surgery for colorectal cancer and might indicate a potential reduction of survival for these patients

Cardiopulmonary exercise test in hypertrophic cardiomyopathy

Understanding the functional limitation in hypertrophic cardiomyopathy, the most common inherited heart disease, is challenging. In addition to the occurrence of disease-related complications, several factors are potential determinants of exercise limitation, including left ventricular hypertrophy, myocardial fiber disarray, left ventricular outflow tract obstruction, microvascular ischemia, and interstitial fibrosis. Furthermore, drugs commonly used in the daily management of these patients may interfere with exercise capacity, especially those with a negative chronotropic effect. Cardiopulmonary exercise testing can safely and objectively evaluate the functional capacity of these patients and help the physician in understanding the mechanisms that underlie this limitation. Features that reduce exercise capacity may predict progression to heart failure in these patients and even the risk of sudden cardiac death

Hypertension in patients with heart failure with reduced ejection fraction

Hypertension (HTN) is a well-known health problem associated with considerable morbidity and mortality and it is an important risk factor for the development of heart failure (HF). These findings support the need for optimizing the antihypertensive strategies to prevent the progression to HF. Interestingly, the progression from HTN to HF, among other things, may be a consequence of inappropriate over-activation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), and the natriuretic peptide system (NPS). In the present review, we will discuss the pathophysiological aspects of the progression from HTN to HF with reduced ejection fraction (HFrEF) and we will focus on the evolution of different pharmacological therapies which are reported to be effective in reducing BP and improving HF outcomes, paying particular attention to the recent trials that have demonstrated the efficacy of the combined therapy of RAAS blockade and Neprilysin (NEP) inhibitor in lowering BP and mediating several beneficial actions within cardiovascular tissues, such as avoiding the worsening of HF

New therapies for arterial hypertension

Arterial hypertension is the most common chronic disease in developed countries and it is the leading risk factor for stroke, ischemic heart disease, congestive heart failure, chronic renal failure and peripheral artery disease. Its prevalence appears to be about 30-45% of the general population. Recent European guidelines estimate that up to 15-20% of the hypertensive patients are not controlled on a dual antihypertensive combination and they require three or more different antihypertensive drug classes to achieve adequate blood pressure control. The guidelines confirmed that diuretics, beta-blockers, calcium-channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are suitable for the initiation and maintenance of antihypertensive treatment, either as monotherapy or in combination therapy. Very few antihypertensive agents have reached the market over the last few years, but no new therapeutic class has really emerged. The long-term adherence to cardiovascular drugs is still low in both primary and secondary prevention of cardiovascular diseases. In particular, the issue of compliance is persistently high in hypertension, despite the fixed-dose combination therapy. As a consequence, a cohort of high-risk hypertensive population, represented by patients affected by refractory and resistant hypertension, can be identified. Therefore, the need of controlling BP in high-risk patients may be addressed, in part, by the development of new drugs, devices and procedures that are designed to treat hypertension and comorbidities. In this review we will comprehensively discuss the current literature on recent therapeutic advances in hypertension, including both medical therapy and interventional procedures

Triple Combination Therapies Based on Olmesartan: A Personalized Therapeutic Approach to Improve Blood Pressure Control

Recent epidemiological surveys have demonstrated that effective and sustained blood pressure (BP) control is achieved in a relatively small proportion of treated hypertensive patients. Indeed, treatment of hypertension represents a key strategy for preventing coronary artery disease, stroke, congestive heart failure and cardiovascular death. Several interventions have been proposed by international guidelines for ameliorating hypertension management and control, mostly including integrated and multi-dimensional pharmacological and non-pharmacological strategies. In particular, numerous evidence demonstrated that a more extensive use of combination therapy may represent a valid therapeutic option for treating hypertensive patients at different risk profile. This strategy has been definitely strengthened by the availability of single pill fixed-dose combinations. Among potential combination therapies, those based on the association of renin-angiotensin system antagonists, thiazide diuretics and calcium channel blockers are very effective in lowering BP levels and well tolerated. We will provide here an overview of clinical evidence supporting the use of triple combination therapy, with a focus on that based on olmesartan medoxomil, a thiazide diuretic (hydrochlorothiazide) and a calcium channel blocker (amlodipine besylate), which is available in multiple dosages. Finally, in view of the recognised importance of single-pill combination therapy for treating hypertension, we will examine the potential benefits of dual (fixed) combination therapy based on olmesartan medoxomil with either thiazide diuretic hydrochlorothiazide or calcium channel blocker amlodipine in terms of efficacy, safety and tolerability profile

Monotherapy and Dual Combination Therapies Based on Olmesartan: A Comprehensive Strategy to Improve Blood Pressure Control

Olmesartan medoxomil is an antihypertensive drug of the class of angiotensin II type 1 (AT1) receptor antagonists (or blockers), characterized by tight and prolonged binding to AT1 receptor compared to other molecules within the same class. These characteristics produce effective and sustained blood pressure reductions in hypertensive patients at different cardiovascular risk profile with a good tolerability profile. After a brief description of the pharmacological characteristics of olmesartan, we will provide a thorough overview of the clinical studies that investigated its efficacy and safety in the clinical management of hypertensive patients both in monotherapy and in dual combination therapies with either thiazide diuretics or calcium channel blockers. These studies demonstrated that olmesartan-based antihypertensive strategy may indeed provide sustained BP control over the 24-h period in a wide proportion of hypertensive patients, thus contributing to a substantial progress in hypertension management. Finally, since growing evidence suggest that olmesartan may also exert potential favourable effects at vascular level, thereby antagonizing the vascular inflammatory process involved in the development and progression of atherosclerosis, the main clinical studies addressing this issue will be also discussed