Early Primary Prevention Research Articles

Melanoma in Northwestern Romania: An Analysis of Epidemiological and Histopathological Characteristics and Associated Risk Factors

Background: Cutaneous melanoma (CM) is a malignant tumor originating from melanocytes. Despite improvements in prevention, Central and Eastern European countries continue to report higher rates of advanced-stage melanoma and lower survival rates. This study aims to characterize CM and the associated risk factors in Northwestern Romania. Methods: This cross-sectional cohort study was conducted in Cluj and Bihor counties. Between January 2023 and May 2024, 172 patients with histopathologically confirmed melanoma completed a standardized questionnaire addressing demographics, sun exposure history, nevi count, and melanoma-specific characteristics. Results: The median age at diagnosis of participants was 44 years. The median Breslow index (BI) was 1.5 mm, and 39% of cases presented with a BI > 2 mm. Superficial spreading melanoma (SSM) was the most common subtype, predominantly affecting women, while nodular melanoma (NM) was more frequent in men. Higher BI was associated with NM and acral lentiginous melanoma (ALM). Limbs were women’s most frequent tumor site, whereas the trunk was predominant in men. Significant associations were observed between younger age at diagnosis and factors such as high nevus count, indoor activity, and smoking status. Rural residents reported a higher history of sunburns compared to urban residents. Conclusions: Our findings underscore the importance of targeted public health interventions to promote early detection and primary prevention of melanoma. Establishing a national melanoma registry is crucial to improving epidemiological surveillance and reducing the burden of melanoma in Romania.

DIAGNOSTIC AND PROGNOSTIC SIGNIFICANCE OF EPSTEIN-BARR VIRUS AND HUMAN PAPILLOMAVIRUS ASSOCIATED WITH THROAT CANCER: A LITERATURE REVIEW

Actuality: Pharyngeal cancer (PhC) is a malignant neoplasm in the oropharynx and nasopharynx associated with Epstein-Barr viruses (EBV) and human papillomavirus (HPV). Both viruses have oncogenic potential, affecting the pathogenesis of PhC. EBV, which infects more than 90% of the population, can cause various benign and malignant diseases. HPV, especially types 16 and 18, is the main oncogenic factor of oropharyngeal cancer (OPhC). The E6 and E7 proteins produced by HPV disrupt the action of tumor suppressors p53 and Rb, which leads to uncontrolled cell proliferation. EBV activates latent proteins and regulates the immune response, whereas HPV affects cell cycle control by inactivating p53 and Rb. HPVinduced PhC has a better prognosis compared to EBV-associated cancer due to higher sensitivity to treatment. Purpose: Systematization of literature data to assess the diagnostic and prognostic significance of EBV and HPV associated with PhC, to improve programs for early diagnosis and primary prevention of head and neck tumors Methods: A literature review has been conducted on the keywords of the study in the PubMed and MedLine databases since 2015. Results: Studies show that EBV and HPV are important in the diagnosis and prognosis of PhC. The EBV presence in tumor cells can mark a more aggressive course of the disease. However, in some cases, it is associated with better treatment results. Patients with HPV-positive tumors have better prognoses and a more favorable response to treatment compared to HPV-negative cases. Both viruses play an important role in the pathogenesis of PhC, and their diagnosis and characterization can significantly affect treatment tactics and prognosis of the outcome of the disease. Conclusion: EBV and HPV play a key role in the pathogenesis of RG, but their mechanisms of action and clinical outcomes differ. EBV is more often associated with nasopharyngeal cancer and HPV with oropharyngeal cancer, and the latter is more common in Western countries and shows a more favorable prognosis. Future research should focus on developing more effective prevention, diagnosis, and treatment methods for these viruses.

Association between Metabolic Disorders and Impaired Kidney Function Thereafter in the Japanese General Population

Plain Language SummaryKidney is an organ of the silence because a symptom of kidney disease appears only in its end stage. However, kidney disease even in its early stage is a risk of cardiovascular events, a leading cause of death worldwide. It is extremely difficult to restore impaired kidney function. Early detection or primary prevention of kidney disease is quite important; thus, identifying individuals with increased risk of developing kidney disease is one of the most attractive approaches to reduce a burden of cardiovascular disease. Metabolic syndrome (MetS) is a condition that several metabolic disorders are clustered, and kidney disease often coexists with a component of metabolic disorders, such as increased blood pressure, impaired glucose tolerance, and dyslipidemia. The present study investigated whether MetS is a risk of kidney disease. A total of 14,917 subjects with normal kidney function were enrolled and followed up for 5 years with the endpoint of kidney disease. During the follow-up, 2,150 participants developed kidney disease and the occurrence of the disease was more frequent in individuals who had MetS at baseline than in those who did not. Moreover, each metabolic disorder was associated with future occurrence of kidney disease and the risk of kidney disease increased with increasing the number of metabolic disorders. Testing for MetS and its components can help identify individuals at increased risk of developing kidney disease.

CHALLENGE IN TREATING OPTIC NEURITIS IN PATIENT WITH CEREBRAL TOXOPLASMOSIS RELATED TO IMMUNOCOMPROMISED CONDITION

Introduction: This study aimed to discuss the prognosis of optic neuritis in a patient with cerebral toxoplasmosis related to an immunocompromised condition. Case Report: A 28-year-old female complained of blurred vision and double vision 2 weeks before admission, accompanied by headache, low extremities weakness, dysphonia, and dysphagia. Visual acuity of both eyes was 6/30 and worsened to 6/60 in a couple of days. Anterior segment examination revealed anisocoria pupil, and RAPD was positive in the left eye. Funduscopic examination showed a blurry margin and hyperemia of the optic nerve head. There was impaired eye movement, indicating oculomotor and abducens nerve palsies. High titer of IgG Antibody Toxoplasma (264) and very low titer of CD4 (<50) with non-reactive HIV rapid test were found in laboratory findings. Multiple ring enhancement was shown in MRI finding. Unfortunately, patient passed away during hospitalization due to respiratory failure. Discussion: Toxoplasmosis-associated optic neuritis is rare and usually becomes potentially serious. Although parasite detection by microscopy and bioassay is considered the gold standard for the diagnosis of toxoplasmosis, clinical diagnosis relies more on serological examination methods. The high proportion of deaths from this disease is mostly caused by late diagnosis of the infection. Conclusion: Optic neuritis that accompanied by systemic disorders needs special attention and comprehensive treatment among multidisciplinary divisions, especially in the immunocompromised condition. Early detection and primary prevention are important to improve prognosis and survival rate.

Optimal cut-off points of anthropometric and body roundness indices associated with diabetes: Persian (Shahedieh) cohort study.

Diabetes is a chronic and concerning health condition that poses a significant public health challenge. Given that preventing, detecting early, and treating T2DM can enhance public health outcomes, the objective of this study was to identify the most effective obesity indices and determine their optimal cut-off points for predicting the risk of T2DM in an Iranian population. This study was conducted on 8,019 male and female participants aged between 35 and 70 years in the context of Shahedieh cohort study. The ROC curve analysis was utilized to determine the optimal cut-off point of each anthropometric index to predict diabetes in age-sex categories. The overall diabetes incidence in the study population was 2.5%, with 2.5% in men and 2.4% in women. In men, significant differences in most of the anthropometric indices were observed between diabetic individuals and healthy counterparts. This study found that for women 45-65, BMI and weight, and for men under 65 years, weight, WHR, BMI, WC, WHTR, AVI, and BRI are efficient T2DM predictors. The AUC of these indices varied from 0.593 (95% CI: 0.510-0.676) to 0.668 (95% CI: 0.586-0.750) in men, and from 0.587 (95% CI: 0.510-0.664) to 0.644 (95% CI: 0.535-0.754) in women. Anthropometric indices and body roundness are simple, inexpensive, and noninvasive means markers to predict the risk of diabetes. Our findings show that most of the studied indices had acceptable prediction power for men except for elderly. For women over 45 years old, weight and BMI are appropriate predictors. It seems that the approach of reducing diabetes incidence through early detection and primary prevention is achievable.

Proportion of ischemic and nonischemic sudden cardiac death by age and sex

Abstract Background Among women the incidence of sudden cardiac death (SCD) is significant, but lower than in men. During the last decades the proportion of nonischemic SCD seems to have increased in both sexes. Coronary artery disease (CAD) have changed to be sickness of elderly women rather than middle-aged men as in women the prevalence and incidence of CAD starts to increase after the menopause. Purpose The aim of this study was to illustrate how the amount and the proportions of ischemic and nonischemic SCD vary between women and men in different age groups. Methods The Fingesture study has systematically collected clinical and autopsy data from SCD victims in Northern Finland between 1998 and 2017. The cohort consists of 5,869 SCD victims. Results Approximately one fifth of the SCD victims were women (21.1%; P<0.001). Three out of four SCDs were ischemic (74.8%; P<0.001) and majority of the ischemic SCD victims were men (79.8%; P=0.005). The mean age of female victims was 70.1±13.1 years and 63.5±11.8 years among male victims (P<0.001). Amongst women one SCD out of 15 occurred to the subject under 50 years of age (6.7%; P<0.001) whereas in men one SCD victim out of nine was under 50 years old (11.4%; P<0.001). A nonischemic SCD was observed in 350 women and in 1,127 men (P<0.001). The proportion of nonischemic death was higher among women than in men in every age group from under 30 years of age to subjects of 84 years old studied in five year periods (Figure 1). Only age group of 65-69 years in women and 60-64 years in men were not statistically significant, otherwise all the P-values were ≤0.003. The difference in proportion of ischemic and non-ischemic SCD was the smallest among subjects of 40-49 years of age amongst the proportion of ischemic SCD increased rapidly both in women and in men as the prevalence of non-ischemic SCD started to decrease (Figure 1). Amongst SCD victims aged 40-44 years 47.9% of the deaths of men (P<0.001) and 41.7% of the deaths of women (P<0.001) were ischemic etiology. Among women aged 50-54 years over half of the SCDs were ischemic (53.1%; P<0.001). The gender difference in proportion of ischemic SCD was actually the smallest in age groups 40-49 years and after 70 years of age, and its largest in the middle in favor of men. (Figure 1). After the age of 70 years the total amount of SCDs started to plateau in men and decrease in the amount of SCDs was seen in men after the age of 75 years as in women the plateau phase was not reached until the age of 80 years (Figure 2). Conclusion Minority of the SCDs occur under the age of 50 years, especially among women. The proportion of nonischemic SCD was higher in women than in men despite the age. However, already in pre- and perimenopausal age the proportion of ischemic SCD in women was remarkable and the amount of ischemic SCD increased until the age of 80 years emphasizing the need of early primary and secondary prevention of CAD also in women not only in men.Figure 1.Figure 2.

Abstract 14196: Prevalence of Ischemic and Nonischemic Sudden Cardiac Death Differs by Sex and Age

Introduction: During the last decades the proportion of nonischemic sudden cardiac death (NI-SCD) seems to have increased in both sexes. In women the incidence of coronary artery disease (CAD) starts to increase after the menopause. Aim: The aim of this study was to illustrate how the amount and the proportions of ischemic SCD (I-SCD) and NI-SCD vary between women and men in different age groups. Methods: The Fingesture study consists systemically collected clinical and autopsy data of 5,869 SCD victims of Northern of Finland (21% women). Results: In women 6.7% of the SCDs occurred at the age < 50 years and in men 11.4% (P<0.001 for both). I-SCDs covered 75% (P<0.001) of the cases of which 80% were men (P=0.005). The proportion of NI-SCDs was higher in women in every age group. Proportion of I-SCDs started to increase rapidly in both sexes at the age of 40-44 years. In women aged 50-54 years 53% of the cases were I-SCDs. The gender difference in proportion of I-SCD was actually the smallest in age groups 40-49 years and after 70 years of age, and its largest in the middle in favor of men. (Figure 1). After the age of 70 years the total amount of SCDs started to plateau in men and decrease in the amount of SCDs was seen in men after the age of 75 years as in women the plateau phase was not reached until the age of 80 years (Figure 2). Conclusions: Minority of the SCDs occur under the age of 50 years, especially in women. The proportion of NI-SCD was higher in women than in men despite the age but the proportion of I-SCD was remarkable already at pre- and perimenopausal age. The amount of I-SCD increased in women until the age of 80 years emphasizing the need of early primary and secondary prevention of CAD also in women not only in men.

Structural characteristic of the model of early detection and primary pre-vention of cerebral stroke among the adult population

In the article, based on the analysis of world literary sources, official statistical data, and the work of international medical organizations, a systematic analysis and generalization of modern world experience regarding the possibilities of improving the system of early detection and primary prevention of brain strokes among the adult population was carried out. Based on this, an optimized model of early detection and primary prevention of brain strokes among the adult population was developed and scientifically substantiated. The optimized model takes into account the existing medical and social problems of people with brain strokes, the existing shortcomings in the measures of early detection and primary prevention of brain strokes among the adult population, and global achievements and developments. The proposed optimized model of early detection and primary prevention of brain strokes was developed on the basis of own research, careful and thorough study and analysis of modern models of work of domestic health care institutions and best practices of other countries. The optimized model consists of six main interconnected and interdependent main activity apparatuses (structural components of the model): conceptual and categorical apparatus (purpose, tasks, principles, priorities, approaches, properties); strategic and operational apparatus (management levels: strategic, tactical, operational); rule-making apparatus (existing legal framework, formation of new rule-making acts); information and communication apparatus (collection and processing of information, formation of a data bank); functional and organizational apparatus (individual, family, group and population level); practical-implementation apparatus (resource-action and subject-object guidelines, achievement of expected results, verification of effective and corrective measures (if necessary)). Keywords: measures of early detection and primary prevention, stroke pathology, optimized model, functional devices.

Investigating the importance of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as potential diagnostic biomarker in Iranian population

BackgroundIn Iran, lung cancer is the third most common type of cancer and its prevalence is increasing rapidly. Identification informative genetic polymorphisms in cancer causing genes including epidermal growth factor receptor (EGFR) as key gene in control of cellular proliferation via intrinsic tyrosine/kinase activity, exonuclease 1 (EXO1) as one of the upregulated gene in different human malignancies and leptin (LEP) participate in carcinogenesis in lung cancer appears to be used as potential genetic markers for predicting lung cancer risk. There is no study about investigate association of the EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer in Iranian population. The aim of this study was investigating the association of EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with risk of lung cancer as a potentially diagnostic biomarker in Iranian population.MethodsIn this case–control study, A total of 100 patients with lung cancer and 100 age and gender-matched healthy controls were recruited into this study and the association between EGFR (− 216G/T), Exo1 (K589E) and LEP (− 2548G/A) gene polymorphisms with the risk of lung cancer was investigated by using PCR–RFLP technique and bioinformatics approach.ResultsThe rs712829 of EGFR gene show that a significant statistical difference between G allele and risk of lung cancer (P = 0.001, OR = 2.976, CI = 95%, 1.557–5.691), in contrast, the T allele and TT genotype show a protective role against the risk of lung cancer. Result of in silico analysis indicated that the rs712829 alter splicing and promoter regulation of EGFR gene and associated with the risk of lung cancer. PCR–RFLP result for rs1047840 of Exo1 gene showed that the AA genotype and A allele of this polymorphism associated with risk of lung cancer, whereas the GG genotype show a protective effect against the risk of lung cancer (P = 0.004, OR = 5.391, CI = 95%, 1.690–17.200). On the other hand, in silico analysis showed that the existence of rs1047840 in Exo1 gene influence lung cancer susceptibility. For rs7799039 of LEP gene, PCR–RFLP analysis showed that, there is no significant association between this polymorphism and the risk of lung cancer.ConclusionThe rs712829 of EGFR gene and rs1047840 of Exo1 are associated with risk of lung cancer among Iranian population and can be used as a potentially candidate biomarker for early detection and primary prevention.

Lipid profile and carotid intima–media thickness in xanthelasma palpebrarum: A case–control study in Northeast India

Background: Xanthelasma palpebrarum (XP) is a common cutaneous xanthoma often associated with dyslipidemia. Carotid intima–media thickness (CIMT) is a non-invasive method of monitoring subclinical atherosclerotic plaque formation and its progression. This study was conducted to assess the cardiovascular comorbidities in patients with XP by measuring the CIMT and serum lipid profile. Materials and Methods: A total of eighty patients aged between 18 and 80 years diagnosed clinically with XP and the same number of apparently healthy, age- and sex-matched controls were included in the study after giving informed consent. Detailed history taking, examinations, and investigations were performed for all patients. Results: Significantly raised triglycerides and LDL levels were seen in 56.3% and 66.3% of the cases, respectively. HDL levels were elevated in 63.8% of the cases and 95% of the controls, which was statistically significant. The mean levels of total cholesterol, triglyceride, LDL, and HDL were 169.68 ± 39.91 mg/dL, 159.68 ± 28.61 mg/dL, 121.23 ± 30.13 mg/dL, and 43.09 ± 8.76 mg/dL, respectively. Elevated CCAIMT and ICAIMT were seen in 87.4% and 72.8% of the cases, respectively, which was significant. Conclusions: There was a significant elevation of triglyceride and LDL and a decrease in HDL among the patients with XP when compared to the controls, thus making lipid profile testing compulsory for all patients with xanthelasma. They also have an increased risk of subclinical atherosclerosis, as assessed by the significantly higher values of CCAIMT and ICAIMT. Hence, all xanthelasma patients should undergo CIMT as a screening procedure for the early detection and primary prevention of cardiovascular complications. Key words: Xanthoma; Xanthelasma palpebrarum; Dyslipidemia; CIMT; Cardiovascular morbidity

Alergia ao Látex em Contexto Ocupacional

Introduction/framework/objectives Latex allergy is recognized as a widespread health problem that assumed serious proportions in the 1990s. Although preventive measures have markedly decreased its incidence, recent studies have shown that it remains an important health problem in certain population groups, particularly in developing countries. This work aims to provide a comprehensive review of the current status of occupational latex allergies. We summarize various aspects of this condition, such as prevalence, risk groups, latex allergens, the diagnostic approach, prevention, and treatment. Methodology A bibliographic review was carried out in January 2023 in the following databases: PubMed/Medline, Cochrane Library, Evidence-based Medicine, Canadian Medical Association, Practice Guidelines and National Guideline Clearinghouse. Content Repeated exposure to latex in an occupational context can lead to worker sensitivity, with a significant clinical and socio-economic impact. We summarize various aspects of this condition, such as prevalence, risk groups, latex allergens, the diagnostic approach, prevention and treatment. Discussion and Conclusions The history of latex allergies has demonstrated that potent allergens such as Natural Rubber Latex proteins can cause rapid immunoglobulin-E-mediated sensitization and clinical allergies, reaching serious proportions in highly exposed individuals. Occupational exposure has a decisive influence on the allergen sensitivity profile, with important clinical and therapeutic consequences. The effectiveness of secondary prevention measures is limited. Thus, it is essential to implement early primary prevention measures in individuals belonging to risk groups, to avoid or minimize exposure to latex allergens. KEYWORDS: Healthcare Professionals, Latex allergy, Latex gloves, Latex hypersensitivity, Natural rubber latex, Occupational diseases, Occupational health, Occupational Medicine.

Number of prior live births is associated with higher arterial stiffness but not its change in older women: the atherosclerosis risk in communities study.

Although studies have demonstrated a J-shaped association between parity and cardiovascular disease (CVD), the association with arterial stiffness is not fully understood. We examined the association between parity and carotid-femoral pulse wave velocity (cfPWV), a measure of central arterial stiffness. We conducted a longitudinal analysis of 1220 women (mean age 73.7 years) who attended the Atherosclerosis Risk in Communities Study visit 5 (2011-2013). At visit 2 (1990-1992), women self-reported parity (number of prior live births), which we categorized as: 0 (never pregnant or pregnant with no live births); 1-2 (referent); 3-4; and 5+ live births. Technicians measured cfPWV at visit 5 (2011-2013) and visit 6 or 7 (2016-2019). Multivariable linear regression modeled the associations of parity with visit 5 cfPWV and cfPWV change between visit 5 and 6/7 adjusted for demographics and potential confounding factors. Participants reported 0 (7.7%), 1-2 (38.7%), 3-4 (40.0%), or 5+ (13.6%) prior live births. In adjusted analyses, women with 5+ live births had a higher visit 5 cfPWV (β=50.6 cm/s, 95% confidence interval: 3.6, 97.7 cm/s) than those with 1-2 live births. No statistically significant associations were observed for other parity groups with visit 5 cfPWV or with cfPWV change. In later life, women with 5+ live births had higher arterial stiffness than those with 1-2 live births, but cfPWV change did not differ by parity, suggesting women with 5+ live births should be targeted for early primary prevention of CVD given their higher arterial stiffness at later-life.

Screening for the prevalence of rheumatic heart disease among school children in Egypt.

In low-income nations, Rheumatic valvular heart disease remains a major cause of morbidity and premature deaths. Accurate prevalence data in Egypt are still lacking yet highly desirable to facilitate health care planning. An cluster sample of school children in eastern Egyptian Governorates was examined clinically and echocardiographically (using abbreviated protocol) for detection of rheumatic valvular heart disease based on 2012 World Heart Federation criteria (the Doppler and the morphological criteria) for diagnosis. According to echocardiography interpretation, participants were categorized as having definite rheumatic heart disease (RHD), borderline RHD or no RHD. A total of 1680 students aged between 6 and 18 years were screened, 119 echocardiographic studies were non-interpretable; so, a total of 1560 studies were evaluated. From the total screened students, 1560 studies were adequate and interpretable according to the criteria specified in the methods section. This revealed a prevalence of 2.3% of the sample with RHD without adding the equivocal cases. The most prevalent lesion as detected by echocardiography was mitral regurgitation (29% of definite RHD cases). Rheumatic valvular heart disease remains prevalent in Egypt and the findings of this study should influence early detection, primary and secondary prevention, and adequate future national health plans.

J-shape relationship between normal fasting plasma glucose and risk of type 2 diabetes in the general population: results from two cohort studies

BackgroundPrevious studies have reported that high fasting plasma glucose (FPG), even that within the normal range, is associated with the risk of type 2 diabetes (T2D). Nevertheless, these findings are limited to specific populations. Thus, studies in the general population are imperative.MethodsThis study included two cohorts comprising 204 640 individuals who underwent physical examinations at the Rich Healthcare Group present at 32 locations in 11 cities of China from 2010 to 2016 and 15 464 individuals who underwent physical tests at the Murakami Memorial Hospital in Japan. Cox regression, restricted cubic spline (RCS), Kaplan–Meier (KM) curves, and subgroup analysis were used to determine the relationship between FPG and T2D. Receiver operating characteristic (ROC) curves were used to evaluate the predictive power of FPG for T2D.ResultsThe mean age of the 220 104 participants (204 640 Chinese and 15 464 Japanese participants) was 41.8 years (41.7 years for the Chinese and 43.7 years for the Japanese participants). During follow-up, 2611 individuals developed T2D (2238 Chinese and 373 Japanese participants). The RCS demonstrated a J-shaped relationship between FPG and T2D risk, with inflexion points of 4.5 and 5.2 for the Chinese and Japanese populations, respectively. Multivariate-adjusted hazard ratio (HR) was 7.75 for FPG and T2D risk after the inflexion point (7.3 for Chinese and 21.13 for Japanese participants).ConclusionsIn general Chinese and Japanese populations, the normal baseline FPG range showed a J-shaped relationship with the risk of T2D. Baseline FPG levels help identify individuals at high risk of T2D and may enable early primary prevention to improve their outcomes.

Genetic Risk Stratification Will Enhance Primary Prevention of Coronary Artery Disease

Coronary artery disease, the number one cause of death in the world, is highly amenable to primary and secondary prevention. Primary prevention is limited because of lack of biomarkers to detect CAD in its asymptomatic phase. Conventional risk factors such as hypertension, are not evident until the 6th or 7th decade, which may be late for primary prevention particularly in males. The recent discovery of genetic risk variants for CAD has the potential through risk stratification to detect individuals most appropriate for primary prevention. First, genetic risk accounts for about 50% of predisposition to CAD; second, it is determined at conception and not influenced by age since DNA does not change in one’s lifetime. Thirdly, genetic risk can be determined at any time from birth onward which is close to ideal for early primary prevention. A review of the literature show genetic risk can be summarized in a single number, referred to as polygenic risk score (PRS), and used to risk stratify for CAD. The PRS has been evaluated in over 1 million individuals and those in the top 20% exhibit a one-to-four-fold greater risk for CAD than those in the bottom 20%. More importantly, clinical studies have shown that decreasing plasma LDL-C or modifying lifestyle decreases the genetic risk for CAD by 50%. The polygenic risk score, obtained from a single blood sample, does not need to be repeated in one’s lifetime. Furthermore, the genetic risk captured by the PRS is relatively independent of the conventional risk factors including family history. The current PRS was determined primarily in individuals of European decent which can be a limitation to its use in other ethnic groups. However, results of trials ongoing in several ethnic groups will soon be available. We propose primary prevention to be initiated early in life in individuals in the top 20% of the PRS. The test is relatively inexpensive and generic drug therapy is also inexpensive. The use of the PRS to risk stratify for CAD would be a paradigm shift for implementation of early primary prevention of CAD.

Association between the metabolic score for insulin resistance (METS-IR) and estimated glomerular filtration rate (eGFR) among health check-up population in Japan: A retrospective cross-sectional study.

This study aimed to investigate the relationship between a new metric-metabolic score for insulin resistance (METS-IR)-and estimated glomerular filtration rate (eGFR) among Japanese participants who underwent health check-ups. We conducted a cross-sectional study that involved participants in a medical health screening program, which was conducted at the Medical Health Check-up Center in Japan. This retrospective study examined the relationship between METS-IR and eGFR among 881 individuals that joined the program between March 1, 2004, and December 31, 2012. Covariates consisted of serum laboratory tests and lifestyle questionnaires. Multivariate linear regression analysis was used to explore the association between METS-IR and eGFR. In addition, subgroup and interaction analyses were done based on age, sex, body mass index (BMI), alcohol use, smoking status, and hyperuricemia. A total of 881 individuals participated in this study. High METS-IR was highly linked with reduced eGFR (adjusted β = -5.04, 95% confidence interval (CI): -7.65 to -2.43), while METS-IR was utilized as a categorical variable inside the multiple regression analysis. A decrease in eGFR of 2.54 units was reported for every 10-unit rise in METS-IR (adjusted β = -2.54, 95% CI: -4.04 to -1.05, P-value = 0.001). Stratified analysis suggested no marked interaction between METS-IR and eGFR across age, sex, BMI, and alcohol consumption groups. However, there was an indication of interaction between METS-IR level, smoking status (P-value = 0.001), and uric level (P-value = 0.011) on eGFR decrease. METS-IR is remarkably associated with eGFR among the participants who underwent health check-ups in Gifu, Japan. Although more studies are required to prove it, METS-IR could be applied as a monitoring index for early screening, primary prevention, and diagnostic and treatment management strategies for chronic kidney disease.

The role of miRNAs in ovarian cancer pathogenesis and therapeutic resistance - A focus on signaling pathways interplay.

One of the most prevalent and lethal forms of gynecological cancer is ovarian cancer (OC), which is often diagnosed in its latter, deadly stages. The OC's high mortality and heterogeneity impede early identification and primary prevention. Thus, numerous studies have looked for biomarkers in OC tissue and blood samples to help early diagnosis and decrease the mortality rate using microRNAs (miRNAs). The miRNAs are short, noncoding RNAs (ncRNAs) that are typically approximately 22 nucleotides in length and act as oncogenic or tumor suppressors via degrading or impeding target mRNA translation. By regulating cellular activities and signaling pathways, miRNAs promote carcinogenesis and the invasiveness of OC cells. In this review, we explore the function of miRNAs in the pathophysiology of OC, their use as biomarkers, future implications, and the direction of future research. The review also underlines the involvement of miRNAs in the most significant pathways affecting the pathogenesis of OC and their relevance to treatment resistance.

Women and Diabetes

Background: Prevalence of undiagnosed diabetes is 53.1% in India as reported by the International Diabetes Federation in 10th Diabetes Atlas 2021. Diabetes is affecting people of all ages and gender. Very high prevalence of abdominal obesity and large percentage of women in Haryana with elevated body mass index (BMI) make it crucial to screen them for type 2 diabetes. Indian Diabetes Risk Score (IDRS) is a proven tool to identify the people at risk of becoming diabetic in future. Early detection and primary prevention are the most effective ways to prevent the rising numbers among women. Objective: This study was conceived to estimate the risk of type 2 diabetes in young working women (25–40 years) using the IDRS tool. Materials and Methods: A descriptive, cross-sectional observational study was followed through with 504 working females in the age bracket 25–40 years. Data were taken down using a structured questionnaire administered through personal interview procedure. Demographics and parameters listed in IDRS such as age, waist circumference, family history of diabetes, and physical activity were itemized in the questionnaire. A purposive random sampling procedure was utilized for getting the numbers. Known cases of diabetes and subjects who refused to sign informed consent were excluded from the survey. Results: About 504 working women completed the survey questionnaire. IDRS scores revealed 18%, 53%, and 29% of the subjects in high-, moderate-, and low-risk brackets, respectively. Waist circumference, sedentary lifestyle, family history, and age were found to be significantly associated with the risk level. Conclusion: The research study brings forward the need for early detection though screening of young women at risk of becoming diabetic in future and necessary steps for primary prevention for the same. It remains imperative to device a comprehensive communication strategy for responsive transitional progression from high risk to absolute healthiness among the young working women.

Lynch Syndrome: From Carcinogenesis to Prevention Interventions.

Simple SummaryPromoting proper preventive interventions to reduce morbidity and mortality is one of the most important challenges pertaining to inherited conditions. Lynch syndrome (LS) is an inherited disorder that predisposes to several kinds of tumor and is responsible for a relevant proportion of human colorectal and endometrial cancers. Recent knowledge has allowed for a better understanding of the genetic cause, pathogenesis, underlying immunological mechanisms, epidemiological distribution, and prevalence of this disease. This opens up unpredictable perspectives of translating such knowledge into validated programs for prevention and surveillance, in order to reduce the health impact of this disease through medical interventions before cancer development. In our review, we summarize the updated guidelines of the screening, surveillance, and risk-reducing strategies for LS patients. Moreover, we present novel opportunities in the treatment and prevention of LS patients through harnessing the immune system using immunocheckpoint inhibitors and vaccines.Lynch syndrome (LS) is the most common inherited disorder responsible for an increased risk of developing cancers at different sites, most frequently in the gastrointestinal and genitourinary tracts, caused by a germline pathogenic variant affecting the DNA mismatch repair system. Surveillance and risk-reducing procedures are currently available and warranted for LS patients, depending on underlying germline mutation, and are focused on relevant targets for early cancer diagnosis or primary prevention. Although pharmacological approaches for preventing LS-associated cancer development were started many years ago, to date, aspirin remains the most studied drug intervention and the only one suggested by the main surveillance guidelines, despite the conflicting findings. Furthermore, we also note that remarkable advances in anticancer drug discovery have given a significant boost to the application of novel immunological strategies such as immunocheckpoint inhibitors and vaccines, not only for cancer treatment, but also in a preventive setting. In this review, we outline the clinical, biologic, genetic, and morphological features of LS as well as the recent three-pathways carcinogenesis model. Furthermore, we provide an update on the dedicated screening, surveillance, and risk-reducing strategies for LS patients and describe emerging opportunities of harnessing the immune system.

Comparison of Joint Modelling and Landmarking Approaches for Dynamic Prediction Using Bootstrap Simulation

Prediction models for clinical outcomes can greatly help clinicians with early diagnosis, cost-effective management and primary prevention of many medical conditions. In conventional prediction models, predictors are typically measured at a fixed time point, either at baseline or at other time point of interest such as biomarker values measured at the most recent follow-up. Dynamic prediction has emerged as a more appealing prediction technique that takes account of longitudinal history of biomarkers for making predictions. We compared prediction performance of two well-known approaches for dynamic prediction, namely joint modelling and landmarking, using bootstrap simulation based on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data with repeat Mini-Mental State Examination (MMSE) scores as the longitudinal biomarker and time-to-Alzheimer’s disease (AD) as the survival outcome. We assessed the performance of both approaches in terms of extended definitions of discrimination and calibration, namely dynamic area under the receiver operating characteristic curve (dynAUC) and expected prediction error (PE). We focused on real data-based bootstrap simulation in an attempt to be as impartial as possible to both methods as landmarking is a pragmatic approach which does not specify a statistical model for the longitudinal markers, and therefore any comparison based on model based data simulation may potentially be more advantageous to joint modelling approach. The dynAUC and PE were compared at landmarks t_{s}=1.0, 1.5, 2.0,text{ and },2.5 years and within a 2-year window from the landmark time points. The optimism corrected estimates of dynAUC for joint modelling were slightly higher (1.26, 3.22, 2.76 and 0.12% higher at the four landmark time points) than that of landmarking approach. Apart from the final landmark point (at 2.5 years), dynamic prediction based on joint models has also performed slightly better in terms of calibration. The expected prediction errors (PE) for joint models were 0.70, 2.56 and 2.04% lower at the first three landmark time points, respectively, compared to the landmarking approach. In general, joint modelling approach has performed better than the landmarking approach in terms of both discrimination (dynAUC) and calibration (PE), although the margin of gain in performance by using joint models over landmarking was relatively small indicating that landmarking approach was close enough, despite not having a precise statistical model characterising the evolution of the longitudinal markers. Future comparative studies should consider extended versions of joint modelling and landmarking approaches which may overcome some of the limitations of the standard methods.