Context base editing for splice correction of IVSI-110 ß-thalassemia.

ß-Thalassemia is brought about by defective ß-globin (HBB [hemoglobin subunit ß]) formation and, in severe cases, requires regular blood transfusion and iron chelation for survival. Genome editing of hematopoietic stem cells allows correction of underlying mutations as curative therapy. As potentially safer alternatives to double-strand-break-based editors, base editors (BEs) catalyze base transitions for precision editing of DNA target sites, prompting us to reclone and evaluate two recently published adenine BEs (ABEs; SpRY and SpG) with relaxed protospacer adjacent motif requirements for their ability to correct the common HBBIVSI-110(G>A) splice mutation. Nucleofection of ABE components as RNA into patient-derived CD34+ cells achieved up to 90% editing of upstream sequence elements critical for aberrant splicing, allowing full characterization of the on-target base-editing profile of each ABE and the detection of differences in on-target insertions and deletions. In addition, this study identifies opposing effects on splice correction for two neighboring context bases, establishes the frequency distribution of multiple BE editing events in the editing window, and shows high-efficiency functional correction of HBBIVSI-110(G>A) for our ABEs, including at the levels of RNA, protein, and erythroid differentiation.

The Overlooked Association Between Nutrition and the Development of Acute Myeloid Leukaemia: A Scoping Review.

PURPOSE OF REVIEW: Acute Myeloid Leukaemia (AML) constitutes a mere 1% of global cancer cases. This scoping review aims to investigate the association between nutrition and the development of AML, providing a foundation for future research in this field. RECENT FINDINGS: A systematic search was conducted across PubMed, EBSCO, Taylor and Francis, Science Direct and Cochrane Library using specific keywords. Inclusion criteria comprised observational studies and clinical trials examining the association between nutrition and the development of AML. Articles selected for analysis were restricted to those published in English between 1990-2023, and available as full text articles. Among the twenty-five articles that were screened, only six met the criteria for data extraction. Four studies did not reveal statistically significant correlations between nutrition and the development of AML, while two studies provided evidence for significant associations. The findings indicated increased AML risk associated with (a) heightened caloric intake, consumption of white potatoes, and red meat (pork and beef) and (b) diminished consumption of vegetables, seafood, nuts, and seeds. The scarcity of comprehensive studies exploring the connection between nutrition and AML, highlights the urgent need for additional research, encompassing pre-clinical studies. This imperative is critical for enhancing our understanding of the molecular mechanisms that underlie the connection between diet and the aetiology of AML. Such knowledge is paramount in advancing effective strategies for both prevention and management of this significant disease.

Focusing on colorectal cancer in young adults (Review).

Colorectal cancer (CRC) ranks as the third leading cause of cancer-related mortality worldwide. Recent years have witnessed an increase in the incidence of CRC among adults <50 years old on a global scale. The increased incidence is associated with several modifiable risk factors, including obesity, type II diabetes, physical inactivity and frequent antibiotic use. In younger individuals, haematochezia and abdominal pain are the most common symptoms, predominantly affecting the left-side colon. While certain cases of early-onset CRC (eoCRC) are associated with a genetic predisposition, the majority result from sporadic mutations in the genes APC, KRAS, BRAF and TP53, which trigger uncontrolled cell proliferation and tumour formation. Colorectal carcinogenesis involves three major pathways: The chromosomal instability (CIN), microsatellite instability and CpG island methylator phenotype pathways. Dysregulation of the CIN pathway accounts for 85% of sporadic cases of eoCRC. Notably, eoCRC exhibits a distinctive molecular profile, characterized by a decreased prevalence of BRAF mutations, an increased prevalence of KRAS mutations and LINE-1 hypomethylation, and involvement of the Microsatellite and Chromosomal Stable pathway. Prevention strategies for eoCRC primarily centre on lifestyle modifications and the development of screening programs targeting younger populations. Further exploration into the molecular mechanisms involved in the identification of novel risk factors associated with eoCRC is imperative. These efforts, in conjunction with the development of specific screening strategies, hold the potential to reduce morbidity and mortality in the future.

Inflammation, Nutrition, and Clinical Outcomes in Breast Cancer Survivors: A Narrative Review.

PURPOSE OF REVIEW: Breast cancer (BC) is the leading cause of death among women aged 44-55 years globally. Pro-inflammatory food can cause tissue-level inflammation, thereby creating a carcinogenic microenvironment and promoting breast cancer. The aim of this review is to provide an overview of the association between inflammation and nutrition and clinical outcomes in breast cancer survivors. RECENT FINDINGS: Pro-inflammatory diets are associated with a higher mortality risk after diagnosis and worse prognosis after treatment. On the other hand, anti-inflammatory diets may improve tissue-level inflammation and improve the overall prognosis and quality of life of survivors. There is strong evidence that the Mediterranean diet in particular is associated with reduced recurrence risk of breast cancer and improved quality of life of survivors. This narrative review provides evidence that there is a strong association between inflammation, dietary habits, and adverse clinical outcomes in breast cancer survivors. It further discusses the current evidence for the role of dietary management in improving clinical outcomes in breast cancer survivors.

Barriers and facilitators for adopting healthy lifestyles in breast cancer survivors: a scoping review protocol.

OBJECTIVE: This scoping review will identify barriers and facilitators for the adoption of 7 healthy lifestyle components by female breast cancer survivors. This will be achieved by mapping the World Cancer Research Fund/American Institute for Cancer Research recommendations and the Lifestyle Medicine pillars. INTRODUCTION: Adherence to healthy lifestyle components (including weight management, physical activity, healthy diet, restorative sleep, avoidance of risky substances, forming and maintaining healthy relationships, and stress management) may improve the quality of life of breast cancer survivors and reduce the risk of adverse patient outcomes. However, cancer survivors' adherence to recommendations of multiple healthy lifestyle components is low, and decreases over time. INCLUSION CRITERIA: The review will consider peer-reviewed studies investigating barriers and facilitators for adopting any of the 7 healthy lifestyle components by female adult (18+ years old) breast cancer survivors (ie, from the time of diagnosis) in community, hospital, and/or cancer care settings, without any geographical restrictions. All study designs and articles published in English will be included. METHODS: The review will follow the JBI methodology for scoping reviews. Databases to be searched will include MEDLINE (PubMed), Embase, CINAHL (EBSCOhost), PsycINFO (Ovid), and the Cochrane Library databases. Articles published from 2007 to the present will be considered since this was the year in which the World Cancer Research Fund/American Institute for Cancer Research recommendations were published. Two independent reviewers will screen the retrieved articles and extract the data. Barriers and facilitators for each lifestyle component will be grouped according to the Theoretical Domain Framework. A narrative summary will explicate the charted data. REVIEW REGISTRATION: Open Science Framework https://osf.io/cn3va.

Recent Developments in Diagnostic and Prognostic Biomarkers for Colorectal Cancer: A Narrative Review.

BACKGROUND: Colorectal cancer was reported as the second most common cause of cancer death worldwide, in the year 2020. This disease is an important public health problem considering its high incidence and mortality rates. SUMMARY: The molecular events that lead to colorectal cancer include genetic and epigenetic abnormalities. Some of the most important molecular mechanisms involved include the APC/ß-catenin pathway, the microsatellite pathway, and the CpG island hypermethylation. Evidence in the literature supports a role for the microbiota in the development of colon carcinogenesis, and specific microbes may contribute to or prevent carcinogenesis. Progress in prevention, screening, and management has improved the overall prognosis of the disease when diagnosed at an early stage; yet metastatic disease continues to have a poor long-term prognosis due to late-stage diagnosis and treatment failure. Biomarkers are a key tool for early detection and prognosis and aim to reduce morbidity and mortality associated with colorectal cancer. The main focus of this narrative review is to provide an update on the recent development of diagnostic and prognostic biomarkers in stool, blood, and tumor tissue samples. KEY MESSAGES: The review focuses on recent investigations in microRNAs, cadherins, Piwi-interacting RNAs, circulating cell-free DNA, and microbiome biomarkers which can be applied for the diagnosis and prognosis of colorectal cancer.

The "not so good" thyroid cancer: a scoping review on risk factors associated with anxiety, depression and quality of life.

The incidence of thyroid cancer has increased in recent years, leading to a growing number of survivors facing lifelong consequences. This scoping review investigated anxiety, depression, and quality of life (QoL) in thyroid cancer survivors compared to the general population, those with benign pathology, and survivors of other types of cancers. Moreover, we aimed to identify the risk factors associated with anxiety, depression, and QoL in thyroid cancer patients. A total of 727 articles were identified through PubMed, ProQuest, Cochrane, and Google Scholar databases, and 68 articles that met the criteria were selected for data extraction. Thyroid cancer survivors have a poorer QoL compared to the general population, population with benign pathology, and survivors of other types of cancer associated with worse clinical outcomes. The main risk factors are grouped into socioeconomic factors, disease-specific factors, management factors, comorbidities, and patient perceptions. Effective communication between the patient and the medical team and behavioral interventions may reduce these risks. Despite the common perception of thyroid cancer as a "good cancer," the findings of this review demonstrate the need to address the risk factors associated with increased anxiety, depression, and lower QoL in survivors.

Hepatocellular Carcinoma: a Narrative Review on Current Knowledge and Future Prospects.

OPINION STATEMENT: Hepatocellular carcinoma is the fourth leading cause of cancer-related deaths worldwide and its associated mortality rate is expected to rise within the next decade. The incidence rate of hepatocellular carcinoma varies significantly across countries and the latter can be attributed to the differences in risk factors that are prevalent across different countries. Some of the risk factors associated with hepatocellular carcinoma include hepatitis B and C infections, non-alcoholic fatty liver disease, and alcoholic liver disease. Regardless of the underlying aetiology, the end result is liver fibrosis and cirrhosis that ultimately progress into carcinoma. The treatment and management of hepatocellular carcinoma is complicated by treatment resistance and high tumor recurrence rates. Early stages of hepatocellular carcinoma are treated with liver resection and other forms of surgical therapy. Advanced stages of hepatocellular carcinoma can be treated with chemotherapy, immunotherapy, and the use of oncolytic viruses and these treatment options can be combined with nanotechnology to improve efficacy and reduce side effects. Moreover, chemotherapy and immunotherapy can be combined to further improve treatment efficacy and overcome resistance. Despite the treatment options available, the high mortality rates provide evidence that current treatment options for advanced-stage hepatocellular carcinoma are not achieving the desired therapeutic goals. Various clinical trials are ongoing to improve treatment efficacy, reduce recurrence rates, and ultimately prolong survival. This narrative review aims to provide an update on our current knowledge and future direction of research on hepatocellular carcinoma.

Impact of the COVID-19 pandemic on total, sex- and age-specific all-cause mortality in 20 countries worldwide during 2020: results from the C-MOR project.

BACKGROUND: To understand the impact of the COVID-19 pandemic on mortality, this study investigates overall, sex- and age-specific excess all-cause mortality in 20 countries, during 2020. METHODS: Total, sex- and age-specific weekly all-cause mortality for 2015-2020 was collected from national vital statistics databases. Excess mortality for 2020 was calculated by comparing weekly 2020 observed mortality against expected mortality, estimated from historical data (2015-2019) accounting for seasonality, long- and short-term trends. Crude and age-standardized rates were analysed for total and sex-specific mortality. RESULTS: Austria, Brazil, Cyprus, England and Wales, France, Georgia, Israel, Italy, Northern Ireland, Peru, Scotland, Slovenia, Sweden, and the USA displayed substantial excess age-standardized mortality of varying duration during 2020, while Australia, Denmark, Estonia, Mauritius, Norway, and Ukraine did not. In sex-specific analyses, excess mortality was higher in males than females, except for Slovenia (higher in females) and Cyprus (similar in both sexes). Lastly, for most countries substantial excess mortality was only detectable (Austria, Cyprus, Israel, and Slovenia) or was higher (Brazil, England and Wales, France, Georgia, Italy, Northern Ireland, Sweden, Peru and the USA) in the oldest age group investigated. Peru demonstrated substantial excess mortality even in the <45 age group. CONCLUSIONS: This study highlights that excess all-cause mortality during 2020 is context dependent, with specific countries, sex- and age-groups being most affected. As the pandemic continues, tracking excess mortality is important to accurately estimate the true toll of COVID-19, while at the same time investigating the effects of changing contexts, different variants, testing, quarantine, and vaccination strategies.

The Association Between Nutrition, Obesity, Inflammation, and Endometrial Cancer: A Scoping Review.

PURPOSE OF REVIEW: Endometrial cancer is the most common gynecological malignancy and represents a notorious threat to women's health worldwide. Endometrial cancer predominantly affects post-menopausal women; yet the prevalence of this disease has been rising also among pre-menopausal women. Poor nutritional habits, inflammation, and obesity may be associated with endometrial cancer (EC) among both pre-menopausal and post-menopausal women and should be further assessed among a wide spectrum of age groups. RECENT FINDINGS: This scoping review explores and reports on primary research studies conducted to investigate the impact of nutrition, inflammation, and/or obesity on endometrial cancer risk among both pre-menopausal and post-menopausal women. Using a predefined protocol in compliance with the PRISMA guidelines, a search was conducted on four separate databases including PubMed, Cochrane Library, ProQuest, and Google Scholar to investigate the association between nutrition, inflammation, obesity, and endometrial cancer. A total of 4862 articles were identified. Following a full article analysis, 27 articles met the full inclusion criteria and were included in the current review. Findings from the literature support a role of nutrition, obesity, and inflammation in the development of EC. The studies included in the current review supported that plant-based, Mediterranean, or ketogenic diets are associated with a lower risk of EC while there is no association between glycemic index and EC risk. On the other hand, increased BMI is associated with a higher risk of EC and there is a positive association between obesity-related pro-inflammatory biomarkers and increased risk for EC development. Further research needs to be conducted to gain more insight into the complex interactions between nutrition, obesity, and inflammation and their association with EC development among pre-, peri-, and post- menopausal women with the ultimate goal to improve management and preventive strategies and achieve reduced prevalence of endometrial cancer.

Optimized Droplet Digital PCR Assay on Cell-Free DNA Samples for Non-Invasive Prenatal Diagnosis: Application to Beta-Thalassemia.

BACKGROUND: Thalassemias are inherited blood disorders and by far one of the most common monogenic diseases globally. Beta-thalassemia has a particularly high prevalence in Cyprus, with the IVSI-110 G>A (HBB:c.93-21G>A) pathogenic variation representing almost 79% of the total carriers. The discovery that 3% to 20% of cell-free fetal DNA (cffDNA) is present in the maternal plasma allowed the development of non-invasive prenatal diagnosis (NIPD) of monogenic diseases, like beta-thalassemia, avoiding the risks of invasive procedures. However, the development of NIPD holds major technical challenges and has not yet reached the clinical setting. METHODS: In this study, we apply droplet digital PCR (ddPCR) coupled with the relative variant dosage approach to develop a NIPD assay for IVSI-110 G>A beta-thalassemia. We have implemented an optimization process for ddPCR to address the challenges of ddPCR assays such as inconclusive rain droplets and thus increase the sensitivity and specificity of the assay. The established protocol was evaluated on 40 maternal plasma samples with a median gestational age of 10 weeks where both parents carried the same pathogenic variation. RESULTS: Thirty-three samples were correctly classified, 6 remained inconclusive, and 1 was misclassified. Our assay exhibited 97.06% accuracy (95% CI, 82.46-99.68), 100% sensitivity (95% CI, 76.84-100), and 95% specificity (95% CI, 75.13-99.87), demonstrating its efficiency for the non-invasive detection of both maternal and paternal alleles. CONCLUSIONS: We have developed an efficient, simple, and cost-effective ddPCR assay for the non-invasive determination of fetal genotype in couples at risk of IVSI-110 G>A beta-thalassemia, bringing NIPD of monogenic diseases closer to the diagnostic setting.

Cervical cancer, geographical inequalities, prevention and barriers in resource depleted countries.

Cervical cancer (CC) remains a current global issue, with >90% of cervical cancer cases being attributed to human papilloma virus (HPV). The highest burden of cervical cancer is reported in resource-depleted geographical areas with a high incidence of HPV infection. Recent developments in primary prevention include vaccinations against specific strains of HPV and the psychoeducation of the public. Yet, despite the availability of vaccinations, there is high incidence of both HPV and cervical cancer in developing countries, which is attributed to a multitude of barriers including inaccessibility to expensive vaccines. With regards to secondary prevention, progress is actively being made to develop more effective methods of screening and to specifically address the needs of low-income countries. In the past few years, more novel screening methods, such as self-assessment kits, immunohistochemistry and methylation marker analysis, have been developed. Barriers to screening in resource-depleted countries include limited financial resources and infrastructure to develop screening programmes, a lack of screening programmes that are accessible to populations, inadequate training of healthcare teams and stigma related to medical examinations performed as part of screening. Developing primary and secondary prevention programs, as well as addressing the barriers involved in countries with low socioeconomic levels, can drastically reduce morbidity and mortality rates associated with cervical cancer, thus reducing the burden associated with this gynaecological malignancy.

Student evaluations of teaching and the development of a comprehensive measure of teaching effectiveness for medical schools.

The evaluation of courses and faculty is of vital importance in all higher education institutions including medical schools. Student Evaluations of Teaching (SETs) commonly take the form of completion of anonymous questionnaires and even though they were originally developed to evaluate courses and programmes, throughout the years they have also been used to measure teaching effectiveness and subsequently to guide important decisions related to the faculty's career progression. Nevertheless, certain factors and biases may influence SET rates and may not measure teaching effectiveness objectively. Although the literature on course and faculty evaluations is well-researched in general higher education, there are concerns with regards to the use of the same tools for evaluation of courses and teachers in medical programmes. Specifically, the SETs in general higher education cannot be directly applied to the structure of courses and delivery of curriculum in medical schools. This review provides an overview of how SETs can be improved at the levels of instrumentation, administration and interpretation. In addition, the paper supports that through the collection and triangulation of data from multiple sources, including students, peers, program administrators and self-awareness via the use of different methods such as peer reviews, focus groups and self-evaluations, it will be possible to develop a comprehensive evaluation system that will present an effective measure of teaching effectiveness, will support the professional development of medical teachers and will improve the quality of teaching in medical education.

The Association Between the Gut Microbiome, Nutritional Habits, Antibiotics, and Gastric Cancer: a Scoping Review.

PURPOSE OF REVIEW: Gastric cancer (GC) represents one of the leading causes of cancer-related deaths worldwide. The prevalence of GC among the younger population has been increasing in recent years, and the latter is associated with late detection and advanced disease status. The factors involved in the development of GC have been the focus of investigation in the past few years; yet no consistent conclusions or preventative solutions have been suggested. This scoping review aims to explore and report on research studies conducted to investigate the association between GC, the gut microbiome, and nutritional habits. RECENT FINDINGS : Using a predefined protocol in compliance with the PRISMA guidelines, a search was conducted on four separate databases including Google Scholar, Cochrane Library, ProQuest, and PubMed to investigate the association between GC, microbiome, and nutrition. A total of 1219 articles were identified through this process. Forty-three articles met the initial screening criteria and following full-article analysis, and 10 articles met the full inclusion criteria and were included in the current review. The results of the study support that there are differences in the gut microbiota between GC patients and healthy controls and that GC patients may have increased microbiota richness and lower diversity compared to healthy controls. In addition, the detection of pre/early GC may be possible through the analysis of the microbiota using fecal sampling. Nutritional habits, probiotics, and antibiotics may also play an important role in affecting GC development. Preliminary studies support a role for the gut microbiota in developing GC. Yet, the lack of sufficient randomized controlled studies investigating the association between GC, the gut microbiota, and nutritional habits demonstrates the need for further clinical research to develop preventative strategies that will aim to reduce the increased incidence of GC among all age groups including younger populations.

Premature mortality attributable to COVID-19: potential years of life lost in 17 countries around the world, January-August 2020.

BACKGROUND: Understanding the impact of the burden of COVID-19 is key to successfully navigating the COVID-19 pandemic. As part of a larger investigation on COVID-19 mortality impact, this study aims to estimate the Potential Years of Life Lost (PYLL) in 17 countries and territories across the world (Australia, Brazil, Cape Verde, Colombia, Cyprus, France, Georgia, Israel, Kazakhstan, Peru, Norway, England & Wales, Scotland, Slovenia, Sweden, Ukraine, and the United States [USA]). METHODS: Age- and sex-specific COVID-19 death numbers from primary national sources were collected by an international research consortium. The study period was established based on the availability of data from the inception of the pandemic to the end of August 2020. The PYLL for each country were computed using 80 years as the maximum life expectancy. RESULTS: As of August 2020, 442,677 (range: 18-185,083) deaths attributed to COVID-19 were recorded in 17 countries which translated to 4,210,654 (range: 112-1,554,225) PYLL. The average PYLL per death was 8.7 years, with substantial variation ranging from 2.7 years in Australia to 19.3 PYLL in Ukraine. North and South American countries as well as England & Wales, Scotland and Sweden experienced the highest PYLL per 100,000 population; whereas Australia, Slovenia and Georgia experienced the lowest. Overall, males experienced higher PYLL rate and higher PYLL per death than females. In most countries, most of the PYLL were observed for people aged over 60 or 65 years, irrespective of sex. Yet, Brazil, Cape Verde, Colombia, Israel, Peru, Scotland, Ukraine, and the USA concentrated most PYLL in younger age groups. CONCLUSIONS: Our results highlight the role of PYLL as a tool to understand the impact of COVID-19 on demographic groups within and across countries, guiding preventive measures to protect these groups under the ongoing pandemic. Continuous monitoring of PYLL is therefore needed to better understand the burden of COVID-19 in terms of premature mortality.

Gut and airway microbiota and their role in COVID-19 infection and pathogenesis: a scoping review.

BACKGROUND: The SARS-CoV-2 virus is responsible for the COVID-19 pandemic. Researchers have been studying the pathogenesis of the virus with the aim to improve our current diagnosis and management strategies. The microbiota have been proposed to play a key role in the pathogenesis of the disease. PURPOSE: To investigate and report on the current available evidence on any associations between the gut and/or airway microbiota and the pathogenesis of COVID-19. METHODS: Using a predefined protocol in compliance with the PRISMA guidelines, a search was conducted on MEDLINE, Science Direct, DOAJ and Cochrane databases on primary research studies assessing the association between COVID-19 infection and the gut and/or airway microbiota. RESULTS: Twenty-two studies were included in the current review; nineteen studies concluded an association between the gut and/or airway dysbiosis and SARS-CoV-2, while 3 studies failed to observe a significant association between the airway microbiome and SARS-CoV-2 infection. Specifically, most studies reported a decrease in microbial diversity and therefore development of intestinal dysbiosis in COVID-19-positive patients compared to healthy controls as well as a possible association between increased intestinal dysbiosis and disease severity. CONCLUSION: During infection with SARS-CoV-2, there are significant changes in the composition of the gut and airway microbiota. Furthermore, the gut microbiota may have a more important role than the airway microbiota in COVID-19 infection. In the future, studies should be more carefully designed to derive more conclusive evidence on the role of the gut and airway microbiota following infection with SARS-CoV-2 which will lead to the formulation of better management strategies in combating COVID-19.

Excess all-cause mortality and COVID-19-related mortality: a temporal analysis in 22 countries, from January until August 2020.

BACKGROUND: This study aimed to investigate overall and sex-specific excess all-cause mortality since the inception of the COVID-19 pandemic until August 2020 among 22 countries. METHODS: Countries reported weekly or monthly all-cause mortality from January 2015 until the end of June or August 2020. Weekly or monthly COVID-19 deaths were reported for 2020. Excess mortality for 2020 was calculated by comparing weekly or monthly 2020 mortality (observed deaths) against a baseline mortality obtained from 2015-2019 data for the same week or month using two methods: (i) difference in observed mortality rates between 2020 and the 2015-2019 average and (ii) difference between observed and expected 2020 deaths. RESULTS: Brazil, France, Italy, Spain, Sweden, the UK (England, Wales, Northern Ireland and Scotland) and the USA demonstrated excess all-cause mortality, whereas Australia, Denmark and Georgia experienced a decrease in all-cause mortality. Israel, Ukraine and Ireland demonstrated sex-specific changes in all-cause mortality. CONCLUSIONS: All-cause mortality up to August 2020 was higher than in previous years in some, but not all, participating countries. Geographical location and seasonality of each country, as well as the prompt application of high-stringency control measures, may explain the observed variability in mortality changes.

Epidemiology, Molecular Mechanisms, and Clinical Trials: an Update on Research on the Association Between Red Meat Consumption and Colorectal Cancer.

PURPOSE OF THE REVIEW: Colorectal cancer is the second most common cause of cancer death in the world. The aim of this review is to provide an update on recent epidemiological studies, the molecular mechanisms involved, and ongoing clinical trials investigating the relationship between red meat consumption and colorectal cancer. RECENT FINDINGS: Evidence in the literature proposes an association between red meat consumption and development of colorectal cancer, and there is some insight with regard to the mechanisms involved. Twenty studies of the IARC report (1990-2015) showed that red meat is positively associated with colorectal cancer whereas 14 studies either supported no positive association or no statistically significant association between red meat consumption and risk for CRC. More recent epidemiological studies conducted from 2016 and onwards provided further evidence that adherence to diets low in red and/or processed meat reduces the risk of colorectal cancer. Evidence from recent studies supports that quantity, doneness, and preparation of red meat play a role in colorectal carcinogenesis. Red meat's degradation products allow for the creation of a pro-inflammatory colonic microenvironment, and the gut microbiome plays a role in colorectal carcinogenesis. Heme, hydrogen sulfide, lipid peroxidation, nitroso compounds, and the bacterium Fusobacterium Nucleatum (as well as possibly other bacteria such as Akkermansia muciniphila, Eubacterium cylindroides, Eubacterium eligens 1 and 2, and Eubacterium rectale 1 and 2) also partake in the process of colorectal carcinogenesis. Several clinical trials are underway investigating the effects of different diets and red meat substitution products on colorectal cancer incidence as well as the underlying molecular mechanisms involved in the process.

Global Perceptions of Women on Breast Cancer and Barriers to Screening.

PURPOSE OF REVIEW: Breast cancer (BC) is a public health dilemma across the globe and a leading cause of mortality for women. Approximately 2.1 million newly diagnosed female BC cases occurred in 2018, comprising nearly 1 in 4 cancer cases among women. When BC is recognized in its early stages, successful treatment results can be achieved. Therefore, screening for BC is of paramount significance and routine screening mammography has been shown to be effective in reducing mortality from BC. Despite being considered a global health issue, national screening programmes are offered only in developed countries and BC is still often diagnosed in advanced stages. RECENT FINDINGS: Disparities in screening exist not only between different countries but also between local and immigrant populations within a particular country. Low screening is attributed to low public awareness as well as numerous social, psychological, and geographical barriers to screening. This review addresses (a) the differences in BC awareness and screening across the globe, (b) the most important barriers and facilitators to screening, and (c) the potential role of health education programmes to increase BC awareness and promote BC screening programmes with the ultimate goal to achieve earlier stage diagnosis of BC.

Keeping a Balance During the Pandemic: a Narrative Review on the Important Role of Micronutrients in Preventing Infection and Reducing Complications of COVID-19.

PURPOSE OF REVIEW: The SARS-CoV-2 (COVID-19) outbreak has manifested into a major public health concern across the globe, affecting particularly the most vulnerable population groups. Currently, there are various clinical trials being conducted to develop effective treatments. It is estimated that it could take one or more years before these drugs pass all safety tests and concrete results with regard to their effectiveness become available. In addition, despite the recent development of vaccines (licensed for use under conditional licenses) and the commencement of COVID-19 vaccination programs in several countries, there is still a need for safe and novel strategies that may reduce the symptomatology and/or prevent the severe complications associated with COVID-19. Natural compounds previously shown to have antiviral potential should be thoroughly considered and investigated for use in prophylactic treatment of COVID-19 due to their availability and safety. RECENT FINDINGS: The current narrative review investigates whether there is evidence in the literature that supplementation with dietary minerals and vitamins may have a role in preventing infection with SARS-CoV-2 or in reducing COVID-19 symptomatology and disease progression. The current evidence from the literature supports that zinc and vitamin C have a potential in reducing the inflammatory response associated with SARS-CoV-2 while folate and vitamin D may have a role in antagonizing the entry of SARs-CoV-2 virus in host calls. Thus, further research should be conducted that could lead to the development of nutritional supplements involving natural and widely available compounds such as zinc, folate, vitamin C, and vitamin D. The latter could be an effective, safe, and inexpensive way to either prevent infection with SARS-CoV-2 and/or lessen the burden of COVID-19 disease.